Benzoheterocyclic derivatives

TECHNICAL FIELD

[0001] The present invention relates to novel benzoheterocyclic derivatives having excellent vasopressin antagonistic activities, vasopressin agonistic activities and oxytocin antagonistic activities.

BACKGROUND ART

[0002] Various benzoheterocyclic compounds analogous to the compounds of the present invention have been known to have anti-vasopressin activities in European Patent Publication No. 0382128 (published on Aug. 15, 1990), WO 91/05549 (published on May 2, 1991), WO 91/16916 (published on Nov. 14, 1991), WO 94/08582 (published on Apr. 28, 15, 1994), WO 94/12476 (published on Jun. 9, 1994), JP-A-5-320135 (published on Dec. 3, 1993), JP-A-6-16643 (published on Jan. 25, 1994), and JP-A-6-157480 (published on Jun. 3, 1994), among which, for example, JP-A-6-16643 discloses the following compounds.

[0003] Some other literatures disclose various benzoheterocyclic compounds which are analogous to the compounds of the present invention in the chemical structure but are different in the pharmacological properties. For example, EP-A-294647 discloses some analogous compounds having positive inotropic action, vasodilating activity and platelet agglutination inhibiting activity, wherein the intermediate compounds of the following formula are also disclosed.

[0004] U.S. Pat. Nos. 3,542,760 (issued Nov. 24, 1970), 3,516,987 (issued Jun. 23, 1970) and 3,458,498 (issued Jul. 29, 1969) disclose also the following compounds which are useful as diuretics, hypoglycemics, antibacterials or anti-convulsants.

[0005] J. Chem. Soc. Perkin Trans., 1, 1985, pp. 1381-1385 discloses the following compounds but does not mention any pharmacological activity thereof.

[0006] Disclosure of Invention

[0007] An object of the present invention is to provide a benzoheterocyclic derivative of the following formula [1]:

[0008] wherein G is a group of the formula:

[0009] or a group of the formula:

[0010] R1 is a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, a hydroxy group, a lower alkanoyloxy group, an amino-lower alkoxy group having optionally a substituent selected from a lower alkyl group and a lower alkanoyl group, an amino group having optionally a lower alkyl substituent, a carboxy-substituted lower alkoxy group, a lower alkoxycarbonyl-substituted lower alkoxy group, or an aminocarbonyl-lower alkoxy group having optionally a lower alkyl substituent,

[0011] R2 is a group of the formula: —NR4R5 (in which R4 and R5 are the same or different, and each a hydrogen atom, a lower alkyl group having optionally a hydroxy substituent or a benzoyl group having optionally a halogen substituent on the phenyl ring); a hydrogen atom; a hydroxy group; a lower alkoxy group; a carboxy-substituted lower alkyl group; a cyano-substituted lower alkyl group; a tetrazolyl-substituted lower alkyl group; a lower alkanoyloxy-substituted lower alkyl group; a lower alkoxycarbonyl-substituted lower alkyl group; an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent; a lower alkoxycarbonyl-substituted lower alkoxy group; a carboxy-substituted lower alkoxy group; a lower alkanoyl group; or a group of the formula: —(O)m—A—(CO)uNR6R7 (in which m and u are each 0 or 1, but both m and n should not be simultaneously 0, A is a lower alkylene group, R6 and R7 are the same or different and each a hydrogen atom, a lower alkoxy group, a lower alkyl group, an amino-substituted lower alkyl group having optionally a lower alkyl substituent, a carbamoyl-substituted lower alkyl group, an adamantyl-substituted lower alkyl group, a lower alkylsulfonyl group, or a phenyl group having optionally a halogen substituent, or R6 and R7 may bind together with the nitrogen atom to which they bond to form a 5- to 7-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or an oxygen atom, said heterocyclic group being optionally substituted by a lower alkyl group or a phenyl-lower alkyl group),

[0012] R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group,

[0013] or R2 and R3 may bind together to form an oxo group, a lower alkylidene group, a lower alkoxy-substituted lower alkylidene group, a lower alkoxycarbonyl-substituted lower alkylidene group, or a phenyl-substituted lower alkylidene group,

[0014] R is a pyridylcarbonyl group which may optionally have a substituent selected from a phenyl group having optionally a lower alkyl substituent and a pyridyl group on the pyridine ring; a 9-oxofluorenyl group; a quinolylcarbonyl group having optionally a phenyl substituent on the quinoline ring; an adamantylcarbonyl group; a thienylcarbonyl group having optionally a phenyl substituent on the thiophene ring; a thiazolylcarbonyl group having optionally a phenyl substituent on the thiazole ring; a cycloalkylcarbonyl group; or a group of the formula:

[0015] (in which p is 1 or 2, R8 is a hydrogen atom, a lower alkyl group, a hydroxy group, an amino group having optionally a lower alkanoyl substituent, a nitro group, a halogen atom or a lower alkoxy group, R9 is a group of the formula: —NR10R11 (in which R10 is a hydrogen atom, a lower alkyl group, or a lower alkanoyl group having optionally a halogen substituent, R11 is a lower alkyl group, a lower alkanoyl group having optionally a substituent selected from a halogen atom and a hydroxy group, a cycloalkyl group, a phenyl-lower alkyl group having optionally a substituent selected from a lower alkyl group and a halogen atom on the phenyl ring, and having optionally a hydroxy substituent on the alkyl moiety, a phenoxy-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, a phenoxy-lower alkanoyl group having optionally a substituent selected from a lower alkyl group, a phenyl group, a lower alkoxy group, a halogen-substituted lower alkyl group, an amino group having optionally a lower alkyl substituent, a nitro group, a lower alkanoyl-substituted amino group and a halogen atom on the phenyl ring, and having optionally a halogen substituent on the lower alkanoyl moiety, an aminocarbonyl group having optionally a substituent selected from a lower alkyl group, a pyridyl-lower alkyl group and a phenyl-lower alkyl group, a lower alkoxycarbonyl group having optionally a halogen substituent, a lower alkoxy-substituted lower alkanoyl group, a lower alkanoyloxy-substituted lower alkanoyl group, a phenoxy-lower alkoxycarbonyl group, a benzofurylcarbonyl group, a benzimidazolylcarbonyl group, a quinolylcarbonyl group, a quinolyloxy-substituted lower alkanoyl group, a phenyl-lower alkoxycarbonyl group, a group of the formula:

[0016] a tetrahydroisoquinolylcarbonyl group, a benzoyl-lower alkyl group, a tetrahydroquinolyloxy-substituted lower alkanoyl group having optionally a substituent selected from a lower alkyl group and an oxo group on the quinoline ring, a lower alkylsulfonyl group, a pyridyl-lower alkoxycarbonyl group, a fluorenyl-lower alkoxycarbonyl group, a lower alkenyloxycarbonyl group, a tetrahydronaphthyloxy-substituted lower alkanoyl group, a phenyl-lower alkenylcarbonyl group, a piperidinyl-lower alkoxycarbonyl group having optionally a substituent selected from a lower alkanoyl group, a lower alkoxycarbonyl group and a lower alkyl group on the piperidine ring, or R10 and R11 may bind together with the nitrogen atom to which they bond to form an isoindoline ring); a hydrogen atom; a lower alkanoyloxy group; a lower alkanoyl group; a lower alkoxy group; a benzoyl group having optionally a lower alkyl substituent on the phenyl ring; a cycloalkyl group; a lower alkyl group; a lower alkylthio group; a phenyl-lower alkanoyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl group having optionally a substituent selected from a lower alkyl group, a lower alkoxy group, a phenyl-lower alkoxy group, a hydroxy group, a lower alkanoyloxy group, a halogen-substituted lower alkoxy group, a nitro group, an amino group having optionally a lower alkanoyl substituent, a phenyl group, and an amino-substituted lower alkoxy group having optionally a lower alkyl substituent; a phenoxy group; a phenoxy-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; an anilino-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a phenyl-lower alkoxy group having optionally a substituent selected from a halogen atom, a lower alkoxycarbonyl group and an aminocarbonyl group having optionally a substituent selected from a lower alkyl group and an amino-substituted lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a benzoyl-lower alkoxy group having optionally a halogen substituent on the phenyl ring; a phenyl-lower alkenyl group having optionally a halogen substituent on the phenyl ring; a benzoyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring; a pyrrolidinyl-substituted lower alkoxy group; a saturated or unsaturated 5- to 11-membered heteromonocyclic or heterobicyclic group having 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom, and said heterocyclic group being optionally substituted by 1 to 3 groups selected from a lower alkyl group, a phenyl group, a lower alkanoyl group, a halogen atom, a phenyl-lower alkyl group and an oxo group; a cycloalkenyl group; a phenyl-lower alkylaminocarbonyl group; an aminosulfonyloxy group having optionally a lower alkyl substituent; a cyano group; or a group of the formula: 13 (A)m—CHR12R13 (in which A is the same as defined above, R12 is a hydrogen atom, a hydroxy group or a lower alkanoyloxy group, R13 is a phenyl group having optionally a lower alkyl substituent or a phenyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, and m is 0 or 1)),

[0017] X is a methylene group, a single bond, a group of the formula: ═CH— or a group of the formula: —NR14— (in which R14 is a hydrogen atom, a lower alkyl group or a lower alkanoyl group),

[0018] Y is a group of the formula: —NRA (in which RA is a hydrogen atom, a lower alkoxycarbonyl-substituted lower alkyl group, a carboxy-substituted lower alkyl group or a group of the formula: —ACONRBRC (in which RB and RC are the same or different and each a hydrogen atom or a lower alkyl group, or RB and RC may bind together with the nitrogen atom to which they bond to form a 5- to 7-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or an oxygen atom, and said heterocyclic group optionally being substituted by a lower alkyl group)),

[0019] provided that when R2 is a group of the formula: —NR4R5 (in which R4 and R5 are the same or different and each a hydrogen atom, a lower alkyl group or a benzoyl group), a hydrogen atom, a hydroxy group, a lower alkoxycarbonyl-substituted lower alkoxy group, a carboxy-substituted lower alkoxy group, a lower alkoxy group, a lower alkanoyloxy-substituted lower alkyl group, a group of the formula: —(O)m—A—(CO)uNR6R7 (m and u are the same as defined above, R6 and R7 are the same or different and each a hydrogen atom or a lower alkyl group, or R6 and R7 may bind together with the nitrogen atom to which they bond to form a 5- to 6-membered saturated heterocyclic group with or without being intervened with another nitrogen atom or an oxygen atom, and said heterocyclic group optionally being substituted by a lower alkyl group), or an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent; or R2 and R3 may bind together to form an oxo group or a lower alkylidene group; and when R is a group of the formula:

[0020] and R8 in said group is a hydrogen atom, a lower alkyl group, a hydroxy group, a halogen atom, a lower alkoxy group or an amino group, then R9 should not be a hydrogen atom, a phenyl-lower alkoxycarbonyl group, nor a group of the formula: —NR10R11 (R11 is a lower alkanoyl group or a phenoxy-lower alkanoyl group having optionally 1 to 3 substituents selected from a lower alkyl group and a lower alkoxy group on the phenyl ring), or

[0021] when R1 is a hydrogen atom, R2 is a hydrogen atom, an amino group, a mono-lower alkylamino group or a di-lower alkylamino group, or R2 and R3 may bind together to form an oxo group, then R9 should not be a phenyl group having optionally a substituent selected from a hydroxy group, a lower alkyl group, a lower alkoxy group and a lower alkanoyloxy group on the phenyl ring, or

[0022] when R9 is a group of the formula:

[0023] (n is 1 or 2), and G is a group of the formula:

[0024] (R2 and R3 are the same as defined above), then X should not be a methylene group nor a group of the formula: ═CH—, or

[0025] when one of R10 and R11 is a hydrogen atom, the other should not be a lower alkyl group,

[0026] or a pharmaceutically acceptable salt thereof.

[0027] The present inventors have intensively studied and have found that the compounds of the formula [1] and a pharmaceutically acceptable salt thereof have excellent vasopressin antagonistic activities, vasopressin agonistic activities and excellent oxytocin antagonistic activities.

[0028] The compounds of the formula [1] of the present invention and a pharmaceutically acceptable salt thereof show excellent vasopressin antagonistic activity, for example, vasodilating activity, hypotensive activity, activity for inhibiting saccharide release in liver, activity for inhibiting growth of mesangium cells, water diuretic activity, platelet agglutination inhibitory activity, inhibitory activity for vomiting, activity for promoting urea excretion, inhibitory activity on secretion of factor VIII, activity for promoting heart function, activity for inhibiting constriction of mesangium cells, inhibitory activity on production of saccharide in liver, inhibitory activity on aldosterone secretion, inhibitory activity on production of endotheline, regulation activity on renin secretion, memory regulation activity, thermoregulation activity, activity for regulating production of prostaglandin, and hence, they are useful as vasodilators, hypotensive agents, water diuretics, platelet agglutination inhibitors, promoters for urea excretion, agent for heart failure, agent for renal failure, etc., and are used in the prophylaxis or treatment of hypertension, edema, ascites, heart failure, renal function disorder, vasopressin parasecretion syndrome (SIADH), hepatocirrhosis, hyponatremia, hypokalemia, diabetes, circulation disorder, motion sickness, water metabolism disorder, renal failure, various diseases associated with ischemic, and the like. Besides, the compounds of the present invention and a pharmaceutically acceptable salt thereof are characteristic in very few side effects and a prolonged action for a long time in a living body.

[0029] The compounds [1] of the present invention and a pharmaceutically acceptable salt thereof also show vasopressin agonistic activities, for example, effects on various urinary disorders, polyuria or hemostatic disorders, and hence, they are useful in the prophylaxis or treatment of pollakisuria, diabetes insipidus, urine incontinence, enuresis, especially nocturnal enuresis, spontaneous hemorrhage, hemophilia, von Willebrand's disease, uremia, congenital and acquired platelet dysfunction, hemostatic derangement caused by surgical procedures or accidental trauma, or hepatic cirrhosis.

[0030] In addition, the compounds [1] of the present invention and a pharmaceutically acceptable salt thereof also show oxytocin antagonistic activities, for example, inhibitory effect on uterine smooth muscle constriction, inhibitory effect on milk secretion, inhibitory effect on synthesis and secretion of prostaglandin, and vasodilating activity, and hence, they are useful in the protection or treatment of oxytocin-associated diseases, especially premature delivery, dysmenorrhea, endometritis, or in stopping labor preparatory to Caesarian delivery.

[0031] The benzoheterocyclic derivatives of the formula [1] of the present invention especially include the following compounds.

[0032] (1) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R2)(R3)—X—, X is a methylene group, R1 is the same as defined above in the definition for the formula [1], R2 is a group of the formula: —NR4R5 (in which R4 and R5 are the same as defined above in the definition for the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, R is a pyridylcarbonyl group having optionally a substituent selected from a phenyl group having optionally a lower alkyl substituent on the phenyl ring and a pyridyl group on the pyridine ring.

[0033] (2) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (1), and R2 is a hydrogen atom.

[0034] (3) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (1), and R2 is a hydroxy group.

[0035] (4) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (1), and R2 is a carboxy-substituted lower alkyl group.

[0036] (5) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (1), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.

[0037] (6) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (1), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0038] (7) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (1), and R2 is a lower alkanoyl group.

[0039] (8) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (1), and R2 and R3 bind together to form an oxo group.

[0040] (9) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (1), and R2 and R3 bind together to form a lower alkylidene group.

[0041] (10) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (1), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.

[0042] (11) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (1), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0043] (12) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (1), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group.

[0044] (13) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R2)(R3)—X—, X is a methylene group, R1 is the same as defined above in the definition for the formula [1], R2 is a group of the formula: —NR4R5 (R4 and R5 are the same as defined above in the definition for the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula:

[0045] (R9 and p are the same as defined above, and R8 is a hydrogen atom).

[0046] (14) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (13), and R2 is a hydrogen atom.

[0047] (15) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (13), and R2 is a hydroxy group.

[0048] (16) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (13), and R2 is a carboxy-substituted lower alkyl group.

[0049] (17) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (13), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.

[0050] (18) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (13), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0051] (19) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (13), and R2 is a lower alkanoyl group.

[0052] (20) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (13), and R2 and R3 bind together to form an oxo group.

[0053] (21) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (13), and R2 and R3 bind together to form a lower alkylidene group.

[0054] (22) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (13), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.

[0055] (23) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (13), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0056] (24) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (13), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group.

[0057] (25) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R2)(R3)—X—, X is a methylene group, R1 is the same as defined above in the formula [1], R2 is a group of the formula: —NR4R5 (R4 and R5 are the same as defined above in the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula:

[0058] (R9 and p are the same as defined above in the formula [1], and R8 is a lower alkyl group).

[0059] (26) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (25), and R2 is a hydrogen atom.

[0060] (27) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (25), and R2 is a hydroxy group.

[0061] (28) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (25), and R2 is a carboxy-substituted lower alkyl group.

[0062] (29) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (25), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.

[0063] (30) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (25), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0064] (31) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (25), and R2 is a lower alkanoyl group.

[0065] (32) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (25), and R2 and R3 bind together to form an oxo group.

[0066] (33) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (25), and R2 and R3 bind together to form a lower alkylidene group.

[0067] (34) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (25), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.

[0068] (35) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (25), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0069] (36) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (25), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group.

[0070] (37) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R2)(R3)—X—, X is a methylene group, R1 is the same as defined above in the formula [1], R2 is a group of the formula: —NR4R5 (R4 and R5 are the same as defined above in the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula:

[0071] (R9 and p are the same as defined above in the formula [1], and R8 is a hydroxy group).

[0072] (38) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (37), and R2 is a hydrogen atom.

[0073] (39) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (37), and R2 is a hydroxy group.

[0074] (40) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (37), and R2 is a carboxy-substituted lower alkyl group.

[0075] (41) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (37), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.

[0076] (42) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (37), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0077] (43) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (37), and R2 is a lower alkanoyl group.

[0078] (44) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (37), and R2 and R3 bind together to form an oxo group.

[0079] (45) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (37), and R2 and R3 bind together to form a lower alkylidene group.

[0080] (46) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (37), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.

[0081] (47) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (37), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0082] (48) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (37), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group.

[0083] (49) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R2)(R3)—X—, X is methylene group, R1 is the same as defined above in the formula [1], R2 is a group of the formula: —NR4R5 (R4 and R5 are the same as defined above in the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula:

[0084] (R9 and p are the same as defined above in the formula [1], and R8 is a nitro group).

[0085] (50) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (49), and R2 is a hydrogen atom.

[0086] (51) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (49), and R2 is a hydroxy group.

[0087] (52) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (49), and R2 is a carboxy-substituted lower alkyl group.

[0088] (53) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (49), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.

[0089] (54) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (49), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0090] (55) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (49), and R2 is a lower alkanoyl group.

[0091] (56) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (49), and R2 and R3 bind together to form an oxo group.

[0092] (57) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (49), and R2 and R3 bind together to form a lower alkylidene group.

[0093] (58) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (49), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.

[0094] (59) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (49), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0095] (60) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (49), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group.

[0096] (61) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R2)(R3)—X—, X is a methylene group, R1 is the same as defined above in the formula [1], R2 is a group of the formula: —NR4R5 (R4 and R5 are the same as defined above in the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula:

[0097] (R9 and p are the same as defined above in the formula [1], and R8 is a halogen atom).

[0098] (62) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (61), and R2 is a hydrogen atom.

[0099] (63) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (61), and R2 is a hydroxy group.

[0100] (64) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (61), and R2 is a carboxy-substituted lower alkyl group.

[0101] (65) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (61), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.

[0102] (66) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (61), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0103] (67) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (61), and R2 is a lower alkanoyl group.

[0104] (68) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (61), and R2 and R3 bind together to form an oxo group.

[0105] (69) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (61), and R2 and R3 bind together to form a lower alkylidene group.

[0106] (70) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (61), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.

[0107] (71) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (61), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0108] (72) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (61), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group.

[0109] (73) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R2)(R3)—X—, X is a methylene group, R1 is the same as defined above in the formula [1], R2 is a group of the formula: —NR4R5 (R4 and R5 are the same as defined above in the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula:

[0110] (R9 and p are the same as defined above in the formula [1], and R8 is a lower alkoxy group).

[0111] (74) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (73), and R2 is a hydrogen atom.

[0112] (75) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (73), and R2 is a hydroxy group.

[0113] (76) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (73), and R2 is a carboxy-substituted lower alkyl group.

[0114] (77) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (73), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.

[0115] (78) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (73), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0116] (79) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (73), and R2 is a lower alkanoyl group.

[0117] (80) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (73), and R2 and R3 bind together to form an oxo group.

[0118] (81) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (73), and R2 and R3 bind together to form a lower alkylidene group.

[0119] (82) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (73), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.

[0120] (83) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (73), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0121] (84) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (73), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group

[0122] (85) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R2)(R3)—X—, X is a group of the formula: —NR14— (R14 is the same as defined above in the formula [1]), R1 is the same as defined above in the formula [1], R2 is a group of the formula: —NR4R5 (R4 and R5 are the same as defined above in the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a pyridylcarbonyl group having optionally a substituent selected from a phenyl group having optionally a lower alkyl substituent on the phenyl ring and a pyridyl group on the pyridine ring.

[0123] (86) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (85), and R2 is a hydrogen atom.

[0124] (87) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (85), and R2 is a hydroxy group.

[0125] (88) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (85), and R2 is a carboxy-substituted lower alkyl group.

[0126] (89) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (85), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.

[0127] (90) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (85), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0128] (91) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (85), and R2 is a lower alkanoyl group.

[0129] (92) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (85), and R2 and R3 bind together to form an oxo group.

[0130] (93) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (85), and R2 and R3 bind together to form a lower alkylidene group.

[0131] (94) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (85), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.

[0132] (95) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (85), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0133] (96) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (85), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group.

[0134] (97) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R2)(R3)—X—, X is a group of the formula: —NR14— (R14 is the same as defined above in the formula [1]), R1 is the same as defined above in the formula [1], R2 is a group of the formula: —NR4R5 (R4 and R5 are the same as defined above in the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula:

[0135] (R9 and p are the same as defined above in the formula [1], and R8 is a hydrogen atom).

[0136] (98) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (97), and R2 is a hydrogen atom.

[0137] (99) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (97), and R2 is a hydroxy group.

[0138] (100) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (97), and R2 is a carboxy-substituted lower alkyl group.

[0139] (101) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (97), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.

[0140] (102) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (97), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0141] (103) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (97), and R2 is a lower alkanoyl group.

[0142] (104) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (97), and R2 and R3 bind together to form an oxo group.

[0143] (105) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (97), and R2 and R3 bind together to form a lower alkylidene group.

[0144] (106) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (97), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.

[0145] (107) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (97), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0146] (108) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (97), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group.

[0147] (109) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R2)(R3)—X—, X is a group of the formula: —NR14— (R14 is the same as defined above in the formula [1]), R1 is the same as defined above in the formula [1], R2 is a group of the formula: —NR4R5 (R4 and R5 are the same as defined above in the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula:

[0148] (R9 and p are the same as defined above in the formula [1], and R8 is a lower alkyl group).

[0149] (110) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (109), and R2 is a hydrogen atom.

[0150] (111) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (109), and R2 is a hydroxy group.

[0151] (112) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (109), and R2 is a carboxy-substituted lower alkyl group.

[0152] (113) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (109), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.

[0153] (114) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (109), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0154] (115) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (109), and R2 is a lower alkanoyl group.

[0155] (116) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (109), and R2 and R3 bind together to form an oxo group.

[0156] (117) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (109), and R2 and R3 bind together to form a lower alkylidene group.

[0157] (118) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (109), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.

[0158] (119) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (109), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0159] (120) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (109), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group.

[0160] (121) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R2)(R3)—X—, X is a group of the formula: —NR14— (R14 is the same as defined above in the formula [1]), R1 is the same as defined above in the formula [1], R2 is a group of the formula: —NR4R5 (R4 and R5 are the same as defined above in the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula:

[0161] (R9 and p are the same as defined above in the formula [1], and R8 is a hydroxy group).

[0162] (122) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (121), and R2 is a hydrogen atom.

[0163] (123) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (121), and R2 is a hydroxy group.

[0164] (124) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (121), and R2 is a carboxy-substituted lower alkyl group.

[0165] (125) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (121), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.

[0166] (126) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (121), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0167] (127) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (121), and R2 is a lower alkanoyl group.

[0168] (128) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (121), and R2 and R3 bind together to form an oxo group.

[0169] (129) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (121), and R2 and R3 bind together to form a lower alkylidene group.

[0170] (130) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (121), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.

[0171] (131) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (121), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0172] (132) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (121), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group.

[0173] (133) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R2)(R3)—X—, X is a group of the formula: —NR14— (R14 is the same as defined above in the formula [1]), R1 is the same as defined above in the formula [1], R2 is a group of the formula: —NR4R5 (R4 and R5 are the same as defined above in the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula:

[0174] (R9 and p are the same as defined above in the formula [1], and R8 is a nitro group).

[0175] (134) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (133), and R2 is a hydrogen atom.

[0176] (135) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (133), and R2 is a hydroxy group.

[0177] (136) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (133), and R2 is a carboxy-substituted lower alkyl group.

[0178] (137) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (133), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.

[0179] (138) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (133), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0180] (139) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (133), and R2 is a lower alkanoyl group.

[0181] (140) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (133), and R2 and R3 bind together to form an oxo group.

[0182] (141) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (133), and R2 and R3 bind together to form a lower alkylidene group.

[0183] (142) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (133), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.

[0184] (143) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (133), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0185] (144) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (133), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group.

[0186] (145) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R2)(R3)—X—, X is a group of the formula: —NR14— (R14 is the same as defined above in the formula [1]), R1 is the same as defined above in the formula [1], R2 is a group of the formula: —NR4R5 (R4 and R5 are the same as defined above in the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula:

[0187] (R9 and p are the same as defined above in the formula [1], and R8 is a halogen atom).

[0188] (146) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (145), and R2 is a hydrogen atom.

[0189] (147) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (145), and R2 is a hydroxy group.

[0190] (148) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (145), and R2 is a carboxy-substituted lower alkyl group.

[0191] (149) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (145), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.

[0192] (150) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (145), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0193] (151) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (145), and R2 is a lower alkanoyl group.

[0194] (152) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (145), and R2 and R3 bind together to form an oxo group.

[0195] (153) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (145), and R2 and R3 bind together to form a lower alkylidene group.

[0196] (154) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (145), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.

[0197] (155) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (145), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0198] (156) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (145), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group.

[0199] (157) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R2)(R3)—X—, X is a group of the formula: —NR14— (R14 is the same as defined above in the formula [1]), R1 is the same as defined above in the formula [1], R2 is a group of the formula: —NR4R5 (R4 and R5 are the same as defined above in the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a group of the formula:

[0200] (R9 and p are the same as defined above in the formula [1], and R8 is a lower alkoxy group).

[0201] (158) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (157), and R2 is a hydrogen atom.

[0202] (159) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (157), and R2 is a hydroxy group.

[0203] (160) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (157), and R2 is a carboxy-substituted lower alkyl group.

[0204] (161) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (157), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.

[0205] (162) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (157), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0206] (163) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (157), and R2 is a lower alkanoyl group.

[0207] (164) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (157), and R2 and R3 bind together to form an oxo group.

[0208] (165) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (157), and R2 and R3 bind together to form a lower alkylidene group.

[0209] (166) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (157), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.

[0210] (167) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (157), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0211] (168) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (157), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group.

[0212] (169) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R2)(R3)—X—, X is a methylene group, R1 is the same as defined above in the formula [1], R2 is a group of the formula: —NR4R5 (R4 and R5 are the same as defined above in the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a 9-oxofluorenyl group.

[0213] (170) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (169), and R2 is a hydrogen atom.

[0214] (171) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (169), and R2 is a hydroxy group.

[0215] (172) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (169), and R2 is a carboxy-substituted lower alkyl group.

[0216] (173) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (169), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.

[0217] (174) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (169), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0218] (175) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (169), and R2 is a lower alkanoyl group.

[0219] (176) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (169), and R2 and R3 bind together to form an oxo group.

[0220] (177) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (169), and R2 and R3 bind together to form a lower alkylidene group.

[0221] (178) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (169), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.

[0222] (179) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (169), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0223] (180) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (169), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group.

[0224] (181) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G is a group of the formula: —C(R2)(R3)—X—, X is a group of the formula: —NR14— (R14 is the same as defined above in the formula [1]), R1 is the same as defined above in the formula [1], R2 is a group of the formula: —NR4R5 (R4 and R5 are the same as defined above in the formula [1]), R3 is a hydrogen atom or a hydroxy-substituted lower alkyl group, and R is a 9-oxofluorenyl group.

[0225] (182) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (181), and R2 is a hydrogen atom.

[0226] (183) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (181), and R2 is a hydroxy group.

[0227] (184) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (181), and R2 is a carboxy-substituted lower alkyl group.

[0228] (185) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (181), and R2 is a lower alkoxycarbonyl-substituted lower alkyl group.

[0229] (186) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (181), and R2 is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent.

[0230] (187) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1, R3 and R are the same as defined in above (181), and R2 is a lower alkanoyl group.

[0231] (188) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (181), and R2 and R3 bind together to form an oxo group.

[0232] (189) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (181), and R2 and R3 bind together to form a lower alkylidene group.

[0233] (190) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (181), and R2 and R3 bind together to form a lower alkoxy-substituted lower alkylidene group.

[0234] (191) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (181), and R2 and R3 bind together to form a lower alkoxycarbonyl-substituted lower alkylidene group.

[0235] (192) A benzoheterocyclic derivative of the formula [1] or a salt thereof, wherein G, X, R1 and R are the same as defined in above (181), and R2 and R3 bind together to form a phenyl-substituted lower alkylidene group

[0236] Each group in the above formula [1] specifically means the following groups.

[0237] The lower alkoxy group includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, pentyloxy, hexyloxy, etc.

[0238] The lower alkyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, methyl, ethyl, propyl, isopropyl, butyl, iso-butyl, tert-butyl, pentyl, hexyl, etc.

[0239] The halogen atom is fluorine atom, chlorine atom, bromine atom or iodine atom.

[0240] The lower alkanoyloxy group includes a straight chain or branched chain alkanoyloxy group having 1 to 6 carbon atoms, for example, formyloxy, acetyloxy, propionyloxy, butyryloxy, isobutyryloxy, pentanoyloxy, tert-butyl-carbonyloxy, hexanoyloxy, and the like.

[0241] The lower alkanoyl group having optionally a halogen substituent includes a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms which may optionally be substituted by 1 to 3 halogen atoms, for example, 2,2,2-trifluoroacetyl, 2,2,2-trichloroacetyl, 2-chloroacetyl, 2-bromoacetyl, 2-fluoroacetyl, 2-iodoacetyl, 2,2-difluoroacetyl, 2,2-dibromoacetyl, 3,3,3-trifluoropropionyl, 3,3,3-trichloropropionyl, 3-chloropropionyl, 2,3-dichloropropionoyl, 4,4,4-trichlorobutyryl, 4-fluorobutyryl, 5-chloropentanoyl, 3-chloro-2-methylpropionyl, 6-bromohexanoyl, 5,6-dibromohexanoyl, and the like.

[0242] The amino-lower alkoxy group having optionally a substituent selected from a lower alkyl group and a lower alkanoyl group includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by an amino group being optionally substituted by 1 to 2 groups selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, aminomethoxy, 2-aminoethoxy, 1-aminoethoxy, 3-aminopropoxy, 4-aminobutoxy, 5-aminopentyloxy, 6-aminohexyloxy, 1,1-dimethyl-2-aminoethoxy, 2-methyl-3-aminopropoxy, acetylaminomethoxy, 1-acetylaminoethoxy, 2-propionylaminoethoxy, 3-isopropionylaminopropoxy, 4-butyrylaminobutoxy, 5-pentanoylaminopentyloxy, 6-hexanoylaminohexyloxy, formylaminomethoxy, methylaminomethoxy, 1-ethylaminoethoxy, 2-propylaminoethoxy, 3-isopropylaminoproxy, 4-butylaminobutoxy, 5-pentylaminopentyloxy, 6-hexylaminohexyloxy, dimethylaminomethoxy, (N-ethyl-N-propylamino)methoxy, 2-(N-methyl-N-hexylamino)ethoxy, and the like.

[0243] The amino group having optionally a lower alkyl substituent includes an amino group which may optionally be substituted by 1 to 2 straight chain or branched chain alkyl groups having 1 to 6 carbon atoms, for example, amino, methylamino, ethylamino, propylamino, isopropylamino, butylamino, tert-butylamino, pentylamino, hexylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino, N-methyl-N-ethylamino, N-ethyl-N-propylamino, N-methyl-N-butylamino, N-methyl-N-hexylamino, and the like.

[0244] The lower alkoxycarbonyl-substituted lower alkoxy group includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, methoxycarbonylmethoxy, 3-methoxycarbonylpropoxy, ethoxycarbonylmethoxy, 3-ethoxycarbonylpropoxy, 4-ethoxycarbonylbutoxy, 5-isopropoxycarbonylpentyloxy, 6-propoxycarbonylhexyloxy, 1,1-dimethyl-2-butoxycarbonylethoxy, 2-methyl-3-tert-butoxycarbonylpropoxy, 2-pentyloxycarbonylethoxy, hexyloxycarbonylmethoxy, and the like.

[0245] The carboxy-substituted lower alkoxy group includes a carboxyalkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, carboxymethoxy, 2-carboxyethoxy, 1-carboxyethoxy, 3-carboxypropoxy, 4-carboxybutoxy, 5-carboxypentyloxy, 6-carboxyhexyloxy, 1,1-dimethyl-2-carboxyethoxy, 2-methyl-3-carboxypropoxy, and the like.

[0246] The aminocarbonyl-lower alkoxy group having a lower alkyl substituent includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by an aminocarbonyl group having 1 to 2 straight chain or branched chain alkyl groups having 1 to 6 carbon atoms, for example, methylaminocarbonylmethoxy, 1-ethylaminocarbonylethoxy, 2-propylaminocarbonylethoxy, 3-isopropylaminocarbonylpropoxy, 4-butylaminocarbonylbutoxy, 5-pentylaminocarbonylpentyloxy, 6-hexylaminocarbonylhexyloxy, dimethylaminocarbonylmethoxy, 3-diethylaminocarbonylpropoxy, diethylaminocarbonylmethoxy, (N-ethyl-N-propylamino)carbonylmethoxy, 2-(N-methyl-N-hexylamino)carbonylethoxy, and the like.

[0247] The benzoyl group having optionally a halogen substituent on the phenyl ring includes a benzoyl group having optionally 1 to 3 halogen substituents on the phenyl ring, for example, benzoyl, 2-chlorobenzoyl, 3-chlorobenzoyl, 4-chlorobenzoyl, 2-fluorobenzoyl, 3-fluorobenzoyl, 4-fluorobenzoyl, 2-bromobenzoyl, 3-bromobenzoyl, 4-bromobenzoyl, 2-iodobenzoyl, 3-iodobenzoyl, 4-iodobenzoyl, 3,4-dichlorobenzoyl, 2,6-dichlorobenzoyl, 2,3-dichlorobenzoyl, 2,4-dichlorobenzoyl, 3,4-difluorobenzoyl, 3,5-dibromobenzoyl, 3,4,5-trichlorobenzoyl, and the like.

[0248] The carboxy-substituted lower alkyl group includes a carboxylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, carboxymethyl, 2-carboxyethyl, 1-carboxyethyl, 3-carboxypropyl, 4-carboxybutyl, 5-carboxypentyl, 6-carboxyhexyl, 1,1-dimethyl-2-carboxyethyl, 2-methyl-3-carboxylpropyl, and the like.

[0249] The lower alkoxycarbonyl-substituted lower alkyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, methoxycarbonylmethyl, 3-methoxycarbonypropyl, ethoxycarbonylmethyl, 3-ethoxycarbonylpropyl, 4-ethoxycarbonylbutyl, 5-isopropoxycarbonylpentyl, 6-propoxycarbonylhexyl, 1,1-dimethyl-2-butoxycarbonylethyl, 2-methyl-3-tert-butoxycarbonylpropyl, 2-pentyloxycarbonylethyl, hexyloxycarbonylmethyl, and the like.

[0250] The amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent includes a straight chain or branched chain alkanoyloxy group having 2 to 6 carbon atoms which is substituted by an amino group having optionally 1 to 2 straight chain or branched chain alkyl groups having 1 to 6 carbon atoms, for example, 2-aminoacetyloxy, 3-aminopropionyloxy, 2-aminopropionyloxy, 4-aminobutyryloxy, 2,2-dimethyl-3-aminopropionyloxy, 5-aminopentanoyloxy, 6-aminohexanoyloxy, 2-methyl-3-aminopropionyloxy, 2-methylaminoacetyloxy, 3-ethylaminopropionyloxyl, 2-propylaminopropionyloxy, 4-isopropylaminobutyryloxy, 4-butylaminobutyryloxy, 4-tert-butyaminobutyryloxy, 5-pentylaminopentanoyloxy, 6-hexylaminohexanoyloxyl, 2-dimethylaminoacetyloxy, 3-diethylaminopropionyloxy, 2-dimethylaminopropionyloxy, 2-(N-ethyl-N-propylamino)acetyloxy, 3-(N-methyl-N-hexylamino)propionyloxy, and the like.

[0251] The lower alkanoyl group includes a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, formyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl, t-butylcarbonyl, hexanoyl, and the like.

[0252] The lower alkylidene group includes a straight chain or branched chain alkylidene group having 1 to 6 carbon atoms, for example, methylidene, ethylidene, propylidene, isopropylidene, butylidene, pentylidene, hexylidene, and the like.

[0253] The lower alkoxycarbonyl-substituted lower alkylidene group includes a straight chain or branched chain alkylidene group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, ethoxycarbonylmethylidene, 2-methoxycarbonylethylidene, 3-isopropoxycarbonylpropylidene, 2-propoxycarbonylisopropylidene, 4-butoxycarbonylbutylidene, 5-pentyloxycarbonylpentylidene, 6-hexyloxycarbonylhexylidene, and the like.

[0254] The lower alkoxy-substituted lower alkylidene group includes a straight chain or branched chain alkylidene group having 1 to 6 carbon atoms which is substituted by a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, methoxymethylidene, 2-ethoxyethylidene, 3-propoxypropylidene, 2-isopropoxyisopropylidene, 4-butoxybutylidene, 5-pentyloxypentylidene, 6-hexyloxyhexylidene, and the like.

[0255] The phenyl-substituted lower alkylidene group includes a straight chain or branched chain alkylidene having 1 to 6 carbon atoms which is substituted by a phenyl group, for example, phenylmethylidene, 2-phenylethylidene, 3-phenylpropylidene, 2-phenylpropylidene, 4-phenylbutylidene, 5-phenylpentylidene, 6-phenylhexylidene, and the like.

[0256] The lower alkylene group includes a straight chain or branched chain alkylene group having 1 to 6 carbon atoms, for example, methylene, ethylene, trimethylene, 2-methyltrimethylene, 2,2-dimethyltrimethylene, 1-methyltrimethylene, methylmethylene, ethylmethylene, tetramethylene, pentamethylene, hexamethylene, etc.

[0257] The amino-substituted lower alkyl group having optionally a lower alkyl substituent includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by an amino group having optionally 1 to 2 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms, for example, aminomethyl, 2-aminoethyl, 1-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl, 1,1-dimethyl-2-aminoethyl, 2-methyl-3-aminopropyl, methylaminomethyl, 1-ethylaminoethyl, 2-propylaminoethyl, 3-isopropylaminopropyl, 4-butylaminobutyl, 5-pentylaminopentyl, 6-hexylaminohexyl, dimethylaminomethyl, 2-diethylaminoethyl, 2-dimethylaminoethyl, (N-ethyl-N-propylamino)methyl, 2-(N-methyl-N-hexylamino)ethyl, and the like.

[0258] The 5- to 7-membered saturated heterocyclic group which is formed by binding R6 and R7 or RB and RC together with the adjacent nitrogen atom to which they bond with or without being intervening with another nitrogen atom or an oxygen atom, for example, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, homopiperazinyl, and the like.

[0259] The above heterocyclic group having a substituent selected from a lower alkyl group and a phenyl-lower alkyl group includes the above mentioned heterocyclic groups having 1 to 3 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, and a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by 1 to 2 phenyl groups, for example, 4-methylpiperazinyl, 3,4-dimethylpiperazinyl, 3-ethylpyrrolidinyl, 2-propylpyrrolidinyl, 1-methylpyrrolidinyl, 3,4,5-trimethylpiperidinyl, 4-butylpiperidinyl, 3-pentylmorpholino, 4-ethylhomopiperazinyl, 4-methylhomopiperazinyl, 4-hexylpiperazinyl, 4-diphenylmethylpiperazinyl, 4-benzylpiperazinyl, 3-methyl-4-benzylpiperazinyl, 3-(2-phenylethyl)pyrrolidinyl, 2-(1-phenylethyl)pyrrolidinyl, 4-(3-phenylpropyl)piperidinyl, 3-(4-phenylbutyl)morpholino, 3-(5-phenylpentyl)piperidinyl, 4-(6-phenylhexyl)piperazinyl, and the like.

[0260] The above heterocyclic group substituted by a lower alkyl group includes the above mentioned heterocyclic groups being substituted by 1 to 3 straight chain or branched chain alkyl groups having 1 to 6 carbon atoms, for example, 4-methylpiperazinyl, 3,4-dimethylpiperazinyl, 3-ethylpyrrolidinyl, 2-propylpyrrolidinyl, 1-methylpyrrolidinyl, 3,4,5-trimethylpiperidinyl, 4-butylpiperidinyl, 3-pentylmorpholino, 4-methylhomopiperazinyl, 4-hexylpiperazinyl, and the like.

[0261] The phenyl group having optionally a lower alkyl substituent includes a phenyl group which may optionally have 1 to 3 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms, for example, phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 3-propylphenyl, 4-butylphenyl, 2-pentylphenyl, 3-hexylphenyl, 3,4-dimethylphenyl, 3,4,5-trimethylphenyl, and the like.

[0262] The phenyl group having optionally a lower alkoxy substituent includes a phenyl group which may optionally have 1 to 3 straight chain or branched chain alkoxy substituents having 1 to 6 carbon atoms, for example, phenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 3-propoxyphenyl, 4-butoxyphenyl, 2-pentyloxyphenyl, 3-hexyloxyphenyl, 2,4-dimethoxyphenyl, 3,4-diethoxyphenyl, 3,4,5-trimethoxyphenyl, and the like.

[0263] The pyridylcarbonyl group having optionally a substituent selected from a phenyl group having optionally a lower alkyl substituent and a pyridyl group on the pyridine ring includes a pyridylcarbonyl group having optionally a substituent selected from a phenyl group having optionally 1 to 3 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms and a pyridyl group on the pyridine ring, for example, pyridylcarbonyl, 2-phenylpyridylcarbonyl, 3-phenylpyridylcarbonyl, 4-phenylpyridylcarbonyl, 2-(2-methylphenyl)pyridylcarbonyl, 3-(2-ethylphenyl)pyridylcarbonyl, 4-(3-propylphenyl)pyridylcarbonyl, 2-(4-butylphenyl)pyridylcarbonyl, 3-(2-pentylphenyl)pyridylcarbonyl, 4-(3-hexylphenyl)pyridylcarbonyl, 2-(3,4-dimethylphenyl)pyridylcarbonyl, 3-(3,4,5-trimethylphenyl)pyridylcarbonyl, 3-(2-pyridyl)pyridylcarbonyl, 2-(3-pyridyl)pyridylcarbonyl, 4-(4-pyridyl)pyridylcarbonyl, and the like.

[0264] The phenyl-lower alkyl group having optionally a substituent selected from a lower alkyl group and a halogen atom on the phenyl ring, and having optionally a hydroxy substituent on the alkyl moiety includes a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, and said alkyl moiety having optionally a hydroxy substituent, and the phenyl ring may optionally have 1 to 3 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and a halogen atom, for example, benzyl, 2-phenylethyl, 1-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 1,1-dimethyl-2-phenylethyl, 5-phenylpentyl, 6-phenylhexyl, 2-methyl-3-phenylpropyl, 2-chlorobenzyl, 2-(3-chlorophenyl)ethyl, 2-fluorobenzyl, 1-(4-chlorophenyl)ethyl, 3-(2-fluorophenyl)propyl, 4-(3-fluorophenyl)butyl, 5-(4-fluorophenyl)pentyl, 1,1-dimethyl-2-(2-bromophenyl)ethyl, 6-(3-bromophenyl)hexyl, 4-bromobenzyl, 2-(2-iodophenyl)ethyl, 1-(3-iodophenyl)ethyl, 3-(4-iodophenyl)propyl, 3,4-dichlorobenzyl, 3,5-dichlorobenzyl, 2,6-dichlorobenzyl, 2,3-dichlorobenzyl, 2,4-dichlorobenzyl, 3,4-difluorobenzyl, 3,5-dibromobenzyl, 3,4,5-trichlorobenzyl, 3,5-dichloro-4-hydroxybenzyl, 3,5-dimethyl-4-hydroxybenzyl, 2-methoxy-3-chlorobenzyl, 2-methylbenzyl, 2-(2-methylphenyl)ethyl, 1-(3-methylphenyl)ethyl, 3-(4-methylphenyl)propyl, 4-(2-ethylphenyl)butyl, 5-(3-propylphenyl)pentyl, 6-(4-butylphenyl)hexyl, 2-(2-pentylphenyl)ethyl, 1-(3-hexylphenyl)ethyl, 3-(3,4-dimethylphenyl)propyl, 2-(3,4,5-trimethylphenyl)ethyl, (2-methyl-6-chlorophenyl)methyl, 3-phenyl-2-hydroxypropyl, 2-phenyl-2-hydroxyethyl, 1-phenyl-1-hydroxymethyl, 3-(4-methylphenyl)-3-hydroxypropyl, 4-(3-chlorophenyl)-4-hydroxybutyl, 5-(2-bromophenyl)-5-hydroxypentyl, 6-(4-fluorophenyl)-6-hydroxyhexyl, and the like.

[0265] The phenoxy-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by a phenoxy group having optionally 1 to 3 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms on the phenyl ring, for example, phenoxymethyl, 2-phenoxyethyl, 1-phenoxyethyl, 4-phenoxybutyl, 5-phenoxypentyl, 6-phenoxyhexyl, 1,1-dimethyl-2-phenoxyethyl, 2-methyl-3-phenoxypropyl, (2-methylphenoxy)methyl, 2-(2-methylphenoxy)ethyl, 3-phenoxypropyl, 4-(3-methylphenoxy)butyl, 5-(2-ethylphenoxy)pentyl, 6-(3-propylphenoxy)hexyl, 4-(butylphenoxy)methyl, 2-(2-pentylphenoxy)ethyl, 1-(3-hexylphenoxy)ethyl, 3-(3,4-dimethylphenoxy)propyl, 2-(3,4,5-trimethylphenoxy)ethyl, and the like.

[0266] The phenoxy-lower alkanoyl group having optionally a substituent selected from a lower alkyl group, a phenyl group, a lower alkoxy group, a halogen-substituted lower alkyl group, an amino group having optionally a lower alkyl substituent, a nitro group, a lower alkanoyl-substituted amino group and a halogen atom on the phenyl ring, and having optionally a halogen substituent on the alkanoyl moiety includes a phenoxyalkanoyl group which may optionally have 1 to 3 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a phenyl group, a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, a straight chain or branched chain alkyl group having 1 to 6 carbon atoms being substituted by 1 to 3 halogen atoms, an amino group having optionally 1 to 2 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms, a nitro group, an amino group substituted by a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms and a halogen atom on the phenyl ring, and the alkanoyl moiety is a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms which may optionally have 1 to 3 halogen substituents, for example, 2-phenoxyacetyl, 2-phenoxypropionyl, 3-phenoxypropionyl, 2-phenoxybutyryl, 4-phenoxybutyryl, 2,2-dimethyl-3-phenoxypropionyl, 5-phenoxypentanoyl, 6-phenoxyhexanoyl, 2-(2-chlorophenoxy)acetyl, 2-(3-chlorophenoxy)acetyl, 2-(4-chlorophenoxy)acetyl, 2-(2-fluorophenoxy)acetyl, 2-(3-fluorophenoxy)acetyl, 3-(4-fluorophenoxy)propionyl, 2-(2-bromophenoxy)propionyl, 4-(3-bromophenoxy)butyryl, 5-(4-bromophenoxy)pentanoyl, 6-(2-iodophenoxy)hexanoyl, 2-(3-iodophenoxy)acetyl, 3-(4-iodophenoxy)propionyl, 4-(3,4-dichlorophenoxy)butyryl, 2-(3,4-dichlorophenoxy)acetyl, 2-(2,6-dichlorophenoxy)acetyl, 2-(2,3-dichlorophenoxy)acetyl, 2-(2,4-dichlorophenoxy)acetyl, 2-(3,4-difluorophenoxy)acetyl, 3-(3,5-dibromophenoxy)propionoyl, 2-(3,4,5-trichlorophenoxy)acetyl, 2-(2-methylphenoxy)acetyl, 2-(3-methylphenoxy)acetyl, 2-(4-methylphenoxy)acetyl, 3-(2-ethylphenoxy)propionyl, 2-(3-ethylphenoxy)propionyl, 4-(4-ethylphenoxy)butyryl, 5-(4-isopropylphenoxy)pentanoyl, 6-(3-butylphenoxy)hexanoyl, 3-(4-pentylphenoxy)propionyl, 2-(4-hexylphenoxy)acetyl, 2-(3,4-dimethylphenoxy)acetyl, 2-(3,4-diethylphenoxy)acetyl, 2-(2,4-dimethylphenoxy)acetyl, 2-(2,5-dimethylphenoxy)acetyl, 2-(2,6-dimethylphenoxy)acetyl, 2-(3,4,5-trimethylphenoxy)acetyl, 2-(3-chloro-4-methylphenoxy)acetyl, 2-(3-dimethylaminophenoxy)acetyl, 2-(3-nitrophenoxy)acetyl, 2-(2-methoxyphenoxy)acetyl, 2-(3-methoxyphenoxy)acetyl, 2-(4-methoxyphenoxy)acetyl, 2-(2-phenylphenoxy)acetyl, 2-(2-trifluoromethylphenoxy)acetyl, 3-(2-aminophenoxy)propionyl, 4-(4-ethylaminophenoxy)butyryl, 5-(2,3-dimethoxyphenoxy)pentanoyl, 6-(2,4,6-trimethoxyphenoxy)hexanoyl, 3-(2-ethoxyphenoxy)propionyl, 4-(3-propoxyphenoxy)propionyl, 2-(4-butoxyphenoxy)acetyl, 3-(4-pentyloxyphenoxy)propionyl, 4-(4-hexyloxyphenoxy)butyryl, 3-(2-nitrophenoxy)propionyl, 4-(4-nitrophenoxy)butyryl, 3-(3-phenylphenoxy)propionyl, 4-(4-phenylphenoxy)butyryl, 5-[3-(2,2,2-trichloroethyl)phenoxy]pentanoyl, 6-[4-(5-bromohexyl)phenoxy]hexanoyl, 2-(4-phenyl-2-methoxyphenoxy)acetyl, 2-(2-phenyl-4-methylphenoxy)acetyl, 2-(2,4,6-trinitrophenoxy)acetyl, 2-(2,4-dinitrophenoxy)acetyl, 2-(3-phenyl-2-dimethylaminophenoxy)acetyl, 2-phenoxy-2,2-difluoroacetyl, 3-(3-dimethylaminophenoxy)-3-bromopropionyl, 4-(3-nitrophenoxy)-3,4,4-trichlorobutyryl, 5-(2-methoxyphenoxy)-5-iodopentanoyl, 2-(2,6-dichlorophenoxy)-2-chloroacetyl, 2-(4-methyl phenoxy)-2,2,-difluoroacetyl, 2-(2-phenylphenoxy)-2,2-difluoroacetyl, 6-(2-phenylphenoxy)-6-bromohexanoyl, 2-(2-acetylaminophenoxy)acetyl, and the like.

[0267] The aminocarbonyl group having optionally a substituent selected from a lower alkyl group, a pyridyl-lower alkyl group and a phenyl-lower alkyl group includes an aminocarbonyl group which may optionally have 1 to 2 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a pyridyl-alkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, butylaminocarbonyl, tert-butylaminocarbonyl, pentylaminocarbonyl, hexylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, dipropylaminocarbonyl, dibutylaminocarbonyl, dipentylaminocarbonyl, dihexylaminocarbonyl, N-methyl-N-ethylaminocarbonyl, N-ethyl-N-propylaminocarbonyl, N-methyl-N-butylaminocarbonyl, N-methyl-N-hexylaminocarbonyl, N-ethyl-N-(pyridylmethyl)aminocarbonyl, N-ethyl-N-benzylaminocarbonyl, benzylaminocarbonyl, (2-phenylethyl)aminocarbonyl, (1-phenylethyl)aminocarbonyl, (3-phenylpropyl)aminocarbonyl, (4-phenybutyl)aminocarbonyl, (5-phenylpentyl)aminocarbonyl, (6-phenylhexyl)aminocarbonyl, N-methyl-N-benzylaminocarbonyl, pyridylmethylaminocarbonyl, (2-pyridylethyl)aminocarbonyl, (3-pyridylpropyl)aminocarbonyl, (4-pyridylbutyl)aminocarbonyl, (5-pyridylpentyl)aminocarbonyl, (6-pyridylhexyl)aminocarbonyl, N-(pyridylmethyl)-N-benzylaminocarbonyl, N-methyl-N-(pyridylmethyl)aminocarbonyl, and the like.

[0268] The benzoyl group having optionally a lower alkyl substituent on the phenyl ring includes a benzoyl group having optionally 1 to 3 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms on the phenyl ring, for example, benzoyl, 2-methylbenzoyl, 3-methylbenzoyl, 4-methylbenzoyl, 2-ethylbenzoyl, 3-propylbenzoyl, 4-butylbenzoyl, 2-pentylbenzoyl, 3-hexylbenzoyl, 3,4-dimethylbenzoyl, 3,4,5-trimethylbenzoyl, and the like.

[0269] The cycloalkyl group includes a cycloalkyl group having 3 to 8 carbon atoms, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, and the like.

[0270] The lower alkylthio group includes a straight chain or branched chain alkylthio group having 1 to 6 carbon atoms, for example, methylthio, ethylthio, propylthio, isopropylthio, butylthio, tert-butylthio, pentylthio, hexylthio, and the like.

[0271] The phenyl-lower alkanoyl group having optionally a lower alkyl substituent on the phenyl ring includes a phenylalkanoyl group wherein the alkanoyl moiety is a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms, which may optionally have 1 to 3 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms on the phenyl ring, for example, 2-phenylacetyl, 3-phenylpropionyl, 4-phenylbutyryl, 2,2-dimethyl-3-phenylpropionyl, 5-phenylpentanoyl, 6-phenylhexanoyl, 2-(2-methylphenyl)acetyl, 2-(3-methylphenyl)acetyl, 2-(4-methylphenyl)acetyl, 3-(2-ethylphenyl)propionyl, 2-(3-ethylphenyl)propionyl, 4-(4-ethylphenyl)butyryl, 5-(4-isopropylphenyl)pentanoyl, 6-(3-butylphenyl)hexanoyl, 3-(4-pentylphenyl)propionyl, 2-(4-hexylphenyl)acetyl, 2-(3,4-dimethylphenyl)acetyl, 2-(3,4-diethylphenyl)acetyl, 2-(2,4-dimethylphenyl)acetyl, 2-(2,5-dimethylphenyl)acetyl, 2-(2,6-dimethylphenyl)acetyl, 2-(3,4,5-trimethylphenyl)acetyl, and the like.

[0272] The halogen-substituted lower alkoxy group includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by 1 to 3 halogen atoms, for example, trifluoromethoxy, trichloromethoxy, chloromethoxy, bromomethoxy, fluoromethoxy, iodomethoxy, difluoromethoxy, dibromomethoxyl, 2-chloroethoxy, 2,2,2-trifluoroethoxy, 2,2,2-trichloroethoxy, 3-bromopropoxy, 3-chloropropoxy, 2,3-dichloropropoxy, 4,4,4-trichlorobutoxy, 4-fluorobutoxy, 5-chloropentyloxy, 3-chloro-2-methylpropoxy, 5-bromohexyloxy, 5,6-dichlorohexyloxy, and the like.

[0273] The amino-substituted lower alkoxy group having optionally a lower alkyl substituent includes a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by an amino group having optionally 1 to 2 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms, for example, aminomethoxy, 2-aminoethoxy, 1-aminoethoxy, 3-aminopropoxy, 4-aminobutoxy, 5-aminopentyloxy, 6-aminohexyloxy, 1,1-dimethyl-2-aminoethoxy, 2-methyl-3-aminopropoxy, methylaminomethoxy, 1-ethylaminoethoxy, 2-propylaminoethoxy, 3-isopropylaminopropoxy, 4-isopropylaminobutoxy, 4-butylaminobutoxy, 4-tert-butylaminobutoxy, 5-pentylaminopentyloxy, 6-hexylaminohexyloxy, dimethylaminomethoxy, 2-diethylaminoethoxy, 2-dimethylaminoethoxy, (N-ethyl-N-propylamino)methoxy, 2-(N-methyl-N-hexylamino)ethoxy, and the like.

[0274] The phenyl group having optionally a substituent selected from a lower alkyl group, a lower alkoxy group, a phenyl-lower alkoxy group, a hydroxy group, a lower alkanoyloxy group, a halogen-substituted lower alkoxy group, a nitro group, an amino group having optionally a lower alkanoyl substituent, a phenyl group and an amino-substituted lower alkoxy group having optionally a lower alkyl substituent includes a phenyl group which may optionally have 1 to 3 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, a hydroxy group, a straight chain or branched chain alkanoyloxy group having 1 to 6 carbon atoms, a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by 1 to 3 halogen atoms, a nitro group, an amino group having optionally a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, a phenyl group, and a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by an amino group having optionally 1 to 2 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms, for example, phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 3-propylphenyl, 4-butylphenyl, 2-pentylphenyl, 3-hexylphenyl, 3,4-dimethylphenyl, 3,4,5-trimethylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 4-ethoxyphenyl, 3-propoxyphenyl, 4-propoxyphenyl, 4-butoxyphenyl, 2-pentyloxyphenyl, 3-hexyloxyphenyl, 2,4-dimethoxyphenyl, 3,4-diethoxyphenyl, 3,4,5-trimethoxyphenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 4-hydroxyphenyl, 2,4-dihydroxyphenyl, 3,4-dihydroxyphenyl, 2,4,6-trihydroxyphenyl, 2-acetyloxyphenyl, 3-propionyloxyphenyl, 2-benzyloxyphenyl, 3-benzyloxyphenyl, 4-benzyloxyphenyl, 2-(2-phenylethoxy)phenyl, 3-(3-phenylpropoxy)phenyl, 4-(4-phenylbutoxy)phenyl, 3-(1-phenylethoxy)phenyl, 2-(5-phenylpentyloxy)phenyl, 3-(6-phenylhexyloxy)phenyl, 2,4-dibenzyloxyphenyl, 3,4-dibenzyloxyphenyl, 3,4,5-tribenzyloxyphenyl, 4-butyryloxyphenyl, 2-pentanoyloxyphenyl, 4-hexanoyloxyphenyl, 2,4-diacetyloxyphenyl, 2,6-diacetyloxyphenyl, 3,4,5-triacetyloxyphenyl, 2-trifluoromethoxyphenyl, 3-(2-chloroethoxy)phenyl, 2-(3-bromopropoxy)phenyl, 4-iodomethoxyphenyl, 2-(2,3-dichloropropoxy)phenyl, 3-(4-fluorobutoxy)phenyl, 4-(3-chloro-2-methylpropoxy)phenyl, 2-(5-bromohexyloxy)phenyl, 3-(5,6-dichlorohexyloxy)phenyl, 4-(2,2,2-trichloroethoxy)phenyl, 2,4-bistrifluoromethoxyphenyl, 2,4,6-tri(trifluoromethoxy)phenyl, 2-aminomethoxyphenyl, 3-(1-aminoethoxy)phenyl, 4-(3-aminopropoxy)phenyl, 2-(4-aminobutoxy)phenyl, 3-(5-aminopentyloxy)phenyl, 4-(6-aminohexyloxy)phenyl, 2-methylaminomethoxyphenyl, 3-(2-propylaminoethoxy)phenyl, 2-(3-isopropylaminopropoxy)phenyl, 4-(4-butylaminobutoxy)phenyl, 2-(5-pentylaminopentyloxy)phenyl, 3-(6-hexylaminohexyloxy)phenyl, 4-dimethylaminomethoxyphenyl, 2-(N-ethyl-N-propylaminomethoxy)phenyl, 2-methyl-4-methoxyphenyl, 2-methyl-6-hydroxyphenyl, 4-methyl-2-(3-bromopropoxy)phenyl, 4-methoxy-2-(3-isopropylaminopropoxy)phenyl, 2-phenylphenyl, 3-phenylphenyl, 4-phenylphenyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 2,3-dinitrophenyl, 2,4,6-trinitrophenyl, 2-aminophenyl, 3-aminophenyl, 4-aminophenyl, 2,4-diaminophenyl, 3,4,5-triaminophenyl, 4-acetylaminophenyl, 2-propionylaminophenyl, 3-butyrylaminophenyl, 4-pentanoylaminophenyl, 4-hexanoylaminophenyl, 2,3-diacetylaminophenyl, 2,4,6-triacetylaminophenyl, and the like.

[0275] The anilino-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring includes an anilino-alkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, which may optionally have 1 to 3 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms on the phenyl ring, for example, anilinomethyl, 2-anilinoethyl, 1-anilinoethyl, 3-anilinopropyl, 4-anilinobutyl, 1,1-dimethyl-2-anilinoethyl, 5-anilinopentyl, 6-anilinohexyl, 2-methyl-3-anilinopropyl, (2-methylanilino)methyl, 2-(2-methylanilino)ethyl, 1-(3-methylanilino)ethyl, 3-(4-methylanilino)propyl, 4-(2-ethylanilino)butyl, 5-(3-propylanilino)pentyl, 6-(4-butylanilino)hexyl, 2-(2-pentylanilino)ethyl, 1-(3-hexylanilino)ethyl, 3-(3,4-dimethylanilino)propyl, 2-(3,4,5-trimethylanilino)ethyl, and the like.

[0276] The phenyl-lower alkoxy group having optionally a substituent selected from a halogen atom, a lower alkoxycarbonyl group and an aminocarbonyl group having optionally a substituent selected from a lower alkyl group and an amino-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring includes a phenylalkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, which may optionally have 1 to 3 substituents selected from a halogen atom, a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, and an aminocarbonyl group having optionally 1 to 2 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by an amino group having optionally 1 to 2 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms on the phenyl ring, for example, phenylmethoxy, 2-phenylethoxy, 1-phenylethoxy, 3-phenylpropoxy, 4-phenylbutoxy, 5-phenylpentyloxy, 6-phenylhexyloxy, 1,1-dimethyl-2-phenylethoxy, 2-methyl-3-phenylpropoxy, (2-chlorophenyl)methoxy, (2-bromophenyl)methoxy, 2-(4-fluorophenyl)ethoxy, 1-(4-bromophenyl)ethoxy, 3-(3-bromophenyl)propoxy, 4-(4-chlorophenyl)butoxy, 5-(2-iodophenyl)pentyloxy, 6-(3-iodophenyl)hexyloxy, (2,6-dichlorophenyl)methoxy, (2,3-dichlorophenyl)methoxy, (2,4-dichlorophenyl)methoxy, (3,4-difluorophenyl)methoxy, (3,4,5-trichlorophenyl)methoxy, (2-methoxycarbonylphenyl)methoxy, (3-ethoxycarbonylphenyl)methoxy, 2-(4-isopropoxycarbonylphenyl)ethoxy, 3-(2-butoxycarbonylphenyl)propoxy, 4-(3-pentyloxycarbonylphenyl)butoxy, 5-(4-hexyloxycarbonylphenyl)pentyloxy, 6-(2-methoxycarbonylphenyl)hexyloxy, (2,4-dimethoxycarbonylphenyl)methoxy, (2,4,6-triethoxycarbonylphenyl)methoxy, (2-carbamoylphenyl)methoxy, 2-(3-methylaminocarbonylphenyl)ethoxy, 1-(4-ethylaminocarbonylphenyl)ethoxy, 3-(2-isopropylaminocarbonylphenyl)propoxy, 4-(3-butylaminocarbonylphenyl)butoxy, 5-(4-pentylaminocarbonylphenyl)pentyloxy, 6-(2-hexylaminocarbonylphenyl)hexyloxy, (2-dimethylaminocarbonylphenyl)methoxy, 2-(3-dibutylaminocarbonylphenyl)ethoxy, 1-(4-dihexylaminocarbonylphenyl)ethoxy, 3-[2-(N-ethyl-N-propylaminocarbonyl)phenyl]propoxy, (2-aminomethylaminocarbonylphenyl)methoxy, 2-[3-(2-aminoethylaminocarbonyl)phenyl]ethoxy, 3-[4-(3-aminopropylaminocarbonyl)phenyl]propoxy, 4-[2-(4-aminobutylaminocarbonyl)phenyl]butoxy, 5-[3-(5-aminopentylaminocarbonyl)phenyl]pentyloxy, 6-[4-(6-aminohexylaminocarbonyl)phenyl]hexyloxy, [2-(N-methyl-N-methylaminomethyl)aminocarbonylphenyl]methoxy, 2-[3-(3-isopropylaminopropylaminocarbonyl)phenyl]ethoxy, 3-{4-[N-propyl-N-(5-pentylaminopentyl)aminocarbonyl]phenyl}propoxy, {2-[N-methyl-N-(2-diethylaminoethyl)aminocarbonyl]phenyl}methoxy, {2-[N,N-bis(diethylaminoethyl)aminocarbonyl]phenyl}methoxy, 4-[3-(N-ethyl-N-propylamino)methylaminocarbonylphenyl]butoxy, 5-[4-{N-[2-(N-methyl-N-hexylamino)ethyl]-N-ethylaminocarbonyl}phenyl]pentyloxy, 6-{4-chloro-2-[N-butyl-N-(6-hexylaminohexyl)aminocarbonyl]phenyl}hexyloxy, [2-bromo-4-(N-hexyl-N-dimethylaminomethyl)aminocarbonylphenyl]methoxy, (2-methoxycarbonyl-3-chlorophenyl)methoxy, and the like.

[0277] The benzoyl-lower alkoxy group having optionally a halogen substituent on the phenyl ring includes a benzoylalkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, which may optionally have 1 to 3 halogen substituents on the phenyl ring, for example, benzoylmethoxy, 2-benzoylethoxy, 1-benzoylethoxy, 3-benzoylpropoxy, 4-benzoylbutoxy, 5-benzoylhexyloxy, 6-benzoylhexyloxy, 1,1-dimethyl-2-benzoylethoxy, 2-methyl-3-benzoylpropoxy, 2-(2-chlorobenzoyl)ethoxy, 1-(3-chlorobenzoyl)ethoxy, (4-chlorobenzoyl)methoxy, 3-(2-fluorobenzoyl)propoxy, 4-(3-fluorobenzoyl)butoxy, 5-(4-fluorobenzoyl)pentyloxy, 6-(2-bromobenzoyl)hexyloxy, 1,1-dimethyl-2-(3-bromobenzoyl)ethoxy, 2-methyl-3-(4-bromobenzoyl)propoxy, (2-iodobenzoyl)methoxy, 2-(3-iodobenzoyl)ethoxy, 3-(4-iodobenzoyl)propoxy, 4-(3,4-dichlorobenzoyl)butoxy, 5-(2,6-dichlorobenzoyl)pentyloxy, 6-(2,3-dichlorobenzoyl)hexyloxy, (2,4-dichlorobenzoyl)methoxy, (3,4-difluorobenzoyl)methoxy, (3,5-dibromobenzoyl)methoxy, (3,4,5-trichlorobenzoyl)methoxy, and the like.

[0278] The phenyl-lower alkenyl group having optionally a halogen substituent on the phenyl ring includes a straight chain or branched chain alkenyl group having 2 to 6 carbon atoms, which is substituted by a phenyl group having optionally 1 to 3 halogen substituents on the phenyl ring, for example, styryl, 3-phenyl-2-propenyl, 3-phenyl-1-propenyl, 4-phenyl-3-butenyl, 4-phenyl-2-butenyl, 4-phenyl-1-butenyl, 5-phenyl-4-pentenyl, 5-phenyl-3-pentenyl, 5-phenyl-2-pentenyl, 5-phenyl-1-pentenyl, 1-methyl-3-phenyl-2-butenyl, 6-phenyl-5-hexenyl, 1-methylstyryl, 2-, 3- or 4-chlorostyryl, 3-(4-bromophenyl)-2-propenyl, 3-(3-fluorophenyl)-1-propenyl, 4-(4-iodophenyl)-3-butenyl, 5-(2-chlorophenyl)-4-pentenyl, 2-methyl-3-bromostyryl, 3,4-dichlorostyryl, 3,4,5-trichlorostyryl, and the like.

[0279] The benzoyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring includes a benzoylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, which may optionally have 1 to 3 alkyl substituents having 1 to 6 carbon atoms on the phenyl ring, for example, benzoylmethyl, 2-benzoylethyl, 1-benzoylethyl, 3-benzoylpropyl, 4-benzoylbutyl, 1,1-dimethyl-2-benzoylethyl, 5-benzoylpentyl, 6-benzoylhexyl, 2-methyl-3-benzoylpropyl, 2-(methylbenzoyl)methyl, 2-(2-methylbenzoyl)ethyl, 1-(3-methylbenzoyl)ethyl, 3-(4-methylbenzoyl)propyl, 4-(2-ethylbenzoyl)butyl, 5-(3-propylbenzoyl)pentyl, 6-(4-butylbenzoyl)hexyl, 2-(2-pentylbenzoyl)ethyl, 1-(3-hexylbenzoyl)ethyl, 3-(3,4-dimethylbenzoyl)propyl, 2-(3,4,5-trimethylbenzoyl)ethyl, and the like.

[0280] The pyrrolidinyl-substituted lower alkoxy group includes a pyrrolidinylalkoxy group wherein the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, (2-pyrrolidinyl)methoxy, 2-(2-pyrrolidinyl)ethoxy, 1-(3-pyrrolidinyl)ethoxy, 3-(2-pyrrolidinyl)propoxy, 4-(3-pyrrolidinyl)butoxy, 5-(2-pyrrolidinyl)pentyloxy, 6-(3-pyrrolidinyl)hexyloxy, 1,1-dimethyl-2-(2-pyrrolidinyl)ethoxy, 2-methyl-3-(3-pyrrolidinyl)propoxy, 5-(1-pyrrolidinyl)pentyloxy, 2-(1-pyrrolidinyl)ethoxy, and the like.

[0281] The phenyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring includes a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, which may optionally have 1 to 3 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms on the phenyl ring, for example, benzyl, 2-phenylethyl, 1-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 1,1-dimethyl-2-phenylethyl, 5-phenylpentyl, 6-phenylhexyl, 2-methyl-3-phenylpropyl, 2-methylbenzyl, 2-(2-methylphenyl)ethyl, 1-(3-methylphenyl)ethyl, 3-(4-methylphenyl)propyl, 4-(2-ethylphenyl)butyl, 5-(3-propylphenyl)pentyl, 6-(4-butylphenyl)hexyl, 2-(2-pentylphenyl)ethyl, 1-(3-hexylphenyl)ethyl, 3-(3,4-dimethylphenyl)propyl, 2-(3,4,5-trimethylphenyl)ethyl, (2-methyl-6-chlorophenyl)methyl, and the like.

[0282] The lower alkoxycarbonyl group includes a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl, hexyoxycarbonyl, and the like.

[0283] The aminocarbonyl group having optionally a substituent selected from a lower alkyl group and an amino-substituted lower alkyl group having optionally a lower alkyl substituent includes an aminocarbonyl group which may optionally have 1 to 2 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by an amino group having optionally 1 to 2 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms, for example, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, butylaminocarbonyl, tert-butylaminocarbonyl, pentylaminocarbonyl, hexylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, dipropylaminocarbonyl, dibutylaminocarbonyl, dipentylaminocarbonyl, dihexylaminocarbonyl, N-methyl-N-ethylaminocarbonyl, N-ethyl-N-propylaminocarbonyl, N-methyl-N-butylaminocarbonyl, N-methyl-N-hexylaminocarbonyl, aminomethylaminocarbonyl, 2-aminoethylaminocarbonyl, 1-aminoethylaminocarbonyl, 3-aminopropylaminocarbonyl, 4-aminobutylaminocarbonyl, 5-aminopentylaminocarbonyl, 6-aminohexylaminocarbonyl, 1,1-dimethyl-2-aminoethylaminocarbonyl, 2-methyl-3-aminopropylaminocarbonyl, methylaminomethylaminocarbonyl, 1-ethylaminoethylaminocarbonyl, 2-propylaminoethylaminocarbonyl, 3-isopropylaminopropylaminocarbonyl, 4-butylaminobutylaminocarbonyl, 5-pentylaminopentylaminocarbonyl, 6-hexylaminohexylaminocarbonyl, dimethylaminomethylaminocarbonyl, 2-diethylaminoethylaminocarbonyl 2-dimethylaminoethylaminocarbonyl, (N-ethyl-N-propylamino)methylaminocarbonyl, 2-(N-methyl-N-hexylamino)ethylaminocarbonyl, N-methyl-N-(2-diethylaminoethyl)aminocarbonyl, N-ethyl-N-(methylaminomethyl)aminocarbonyl, and the like.

[0284] The lower alkyl group having optionally a hydroxy substituent includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which may optionally have 1 to 3 hydroxy substituents, for example, hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxypentyl, 5-hydroxypentyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, 2-methyl-3-hydroxypropyl, and the like.

[0285] The carbamoyl-lower alkyl group includes a carbamoylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, carbamoylmethyl, 2-carbamoylethyl, 1-carbamoylethyl, 3-carbamoylpropyl, 4-carbamoylbutyl, 5-carbamoylpentyl, 6-carbamoylhexyl, 1,1-dimethyl-2-carbamoylethyl, 2-methyl-3-carbamoylpropyl, and the like.

[0286] The adamantyl-substituted lower alkyl group includes an adamantyl-alkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, adamantylmethyl, 2-adamantylethyl, 1-adamantylethyl, 3-adamantylpropyl, 4-adamantylbutyl, 5-adamantylpentyl, 6-adamantylhexyl, 1,1-dimethyl-2-adamantylethyl, 2-methyl-3-adamantylpropyl, and the like.

[0287] The lower alkylsulfonyl group includes an alkylsulfonyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, tert-butylsulfonyl, pentylsulfonyl, hexylsulfonyl, and the like.

[0288] The hydroxy-substituted lower alkyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which have 1 to 3 hydroxy substituents, for example, hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxypentyl, 5-hydroxypentyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, 2-methyl-3-hydroxypropyl, and the like.

[0289] The phenyl-lower alkyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, which is substituted by 1 to 2 phenyl groups, for example, benzyl, 2-phenylethyl, 1-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 5-phenylpentyl, 6-phenylhexyl, 1,1-dimethyl-2-phenylethyl, 2-methyl-3-phenylpropyl, diphenylmethyl, 2,2-diphenylethyl, and the like.

[0290] The quinolylcarbonyl group having optionally a phenyl substituent on the quinoline ring includes, for example, quinolylcarbonyl, 2-phenylquinolylcarbonyl, 3-phenylquinolylcarbonyl, 4-phenylquinolylcarbonyl, 5-phenylquinolylcarbonyl, 6-phenylquinolylcarbonyl, 7-phenylquinolylcarbonyl, 8-phenylquinolylcarbonyl, and the like.

[0291] The thienylcarbonyl group having optionally a phenyl substituent on the thiophene ring includes, for example, thienylcarbonyl, 2-phenylthienylcarbonyl, 3-phenylthienylcarbonyl, 4-phenylthienylcarbonyl, and the like.

[0292] The thiazolylcarbonyl group having optionally a phenyl substituent on the thiazole ring includes, for example, thiazolylcarbonyl, 2-phenylthiazolylcarbonyl, 4-phenylthiazolylcarbonyl, 5-phenylthiazolylcarbonyl, and the like.

[0293] The cycloalkylcarbonyl group includes a cycloalkylcarbonyl group having 3 to 8 carbon atoms in the cycloalkyl moiety, for example, cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl, cycloheptylcarbonyl, cyclooctylcarbonyl, and the like.

[0294] The lower alkanoyl group having optionally a substituent selected from a halogen atom and a hydroxy group includes a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms which may optionally have 1 to 3 substituents selected from a halogen atom and a hydroxy group, for example, in addition to the above-mentioned lower alkanoyl groups having optionally a halogen substituent, 2-hydroxyacetyl, 3-hydroxypropionyl, 2-hydroxypropionyl, 4-hydroxybutyryl, 5-hydroxypentanoyl, 6-hydroxyhexanoyl, 2,2-dimethyl-3-hydroxypropionyl, and the like.

[0295] The halogen-substituted lower alkyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms which is substituted by 1 to 3 halogen atoms, for example, trifluoromethyl, trichloromethyl, chloromethyl, bromomethyl, fluoromethyl, iodomethyl, difluoromethyl, dibromomethyl, 2-chloroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 3-bromopropyl, 3-chloropropyl, 2,3-dichloropropyl, 4,4,4-trichlorobutyl, 4-fluorobutyl, 5-chloropentyl, 3-chloro-2-methylpropyl, 5-bromohexyl, 5,6-dichlorohexyl, and the like.

[0296] The amino group having optionally a lower alkyl substituent includes an amino group having optionally 1 to 2 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms, for example, amino, methylamino, ethylamino, propylamino, isopropylamino, butylamino, tert-butylamino, pentylamino, hexylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino, N-methyl-N-ethylamino, N-ethyl-N-propylamino, N-methyl-N-butylamino, N-methyl-N-hexylamino, and the like.

[0297] The lower alkoxycarbonyl group having optionally a halogen substituent includes a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, which may optionally have 1 to 3 halogen substituents, for example, in addition to the above-mentioned lower alkoxycarbonyl groups, trifluoromethoxycarbonyl, trichloromethoxycarbonyl, chloromethoxycarbonyl, bromomethoxycarbonyl, fluoromethoxycarbonyl, iodomethoxycarbonyl, difluoromethoxycarbonyl, dibromomethoxycarbonyl, 2-chloroethoxycarbonyl, 2,2,2-trifluoroethoxycarbonyl, 2,2,2-trichloroethoxycarbonyl, 3-bromopropoxy, 3-chloropropoxy, 2,3-dichloropropoxy, 4,4,4-trichlorobutoxycarbonyl, 4-fluorobutoxycarbonyl, 5-chloropentyloxycarbonyl, 3-chloro-2-methylpropoxycarbonyl, 5-bromohexyloxycarbonyl, 5,6-dichlorohexyloxycarbonyl, and the like.

[0298] The lower alkoxy-substituted lower alkanoyl group includes an alkoxyalkanoyl group wherein the alkanoyl moiety is a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms and the alkoxy moiety is a straight chain or branched chain alkoxy group having 1 to 6 carbon atoms, for example, 2-methoxyacetyl, 3-methoxypropionyl, 2-ethoxyacetyl, 3-ethoxypropionyl, 4-ethoxybutyryl, 3-propoxypropionyl, 2-methoxypropionyl, 6-propoxyhexanoyl, 5-isopropoxypentanoyl, 2,2-dimethyl-3-butoxypropionyl, 2-methyl-3-tert-butoxypropionyl, 2-pentyloxyacetyl, 2-hexyloxyacetyl, and the like.

[0299] The lower alkanoyloxy-substituted lower alkanoyl group includes an alkanoyloxyalkanoyl group wherein the alkanoyl moieties are a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms which is substituted by a straight chain or branched chain alkanoyloxy group having 1 to 6 carbon atoms, for example, 2-acetyloxyacetyl, 3-acetyloxypropionyl, 2-propionyloxyacetyl, 3-propionyloxypropionyl, 4-propionyloxybutyryl, 3-butyryloxypropionyl, 2-acetyloxypropionyl, 6-propionyloxyhexanoyl, 5-butyryloxypentanoyl, 2,2-dimethyl-3-butyryloxypropionyl, 2-pentanoyloxyacetyl, 2-hexanoyloxyacetyl, and the like.

[0300] The quinolyloxy-substituted alkanoyl group includes a quinolyloxyalkanoyl group wherein the alkanoyl moiety is a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms, for example, 2-quinolyloxyacetyl, 3-quinolyloxypropionyl, 2-quinolyloxypropionyl, 4-quinolyloxybutyryl, 2,2-dimethyl-3-quinolyloxypropionyl, 5-quinolyloxypentanoyl, 6-quinolyloxyhexanoyl, and the like.

[0301] The phenyl-lower alkoxycarbonyl group includes a phenylalkoxycarbonyl group wherein the alkoxycarbonyl moiety is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, benzyloxycarbonyl, 2-phenylethoxycarbonyl, 1-phenylethoxycarbonyl, 3-phenylpropoxycarbonyl, 4-phenylbutoxycarbonyl, 5-phenylpentyloxycarbonyl, 6-phenylhexyloxycarbonyl, 1,1-dimethyl-2-phenylethoxycarbonyl, 2-methyl-3-phenylpropoxycarbonyl, and the like.

[0302] The benzoyl-lower alkyl group includes a benzoylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, benzoylmethyl, 2-benzoylethyl, 1-benzoylethyl, 3-benzoylpropyl, 4-benzoylbutyl, 5-benzoylpentyl, 6-benzoylhexyl, 1,1-dimethyl-2-benzoylethyl, 2-methyl-3-benzoylpropyl, and the like.

[0303] The tetrahydroquinolyloxy-substituted lower alkanoyl group having optionally a substituent selected from a lower alkyl group and an oxo group on the quinoline ring includes a straight chain or branched chain alkanoyl group having 2 to 6 carbon atoms, which is substituted by a tetrahydroquinolyloxy group having optionally 1 to 3 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and an oxo group on the quinoline ring, for example, 2-tetrahydroquinolyloxyacetyl, 3-tetrahydroquinolyloxypropionyl, 2-tetrahydroquinolyloxypropionyl, 4-tetrahydroquinolyloxybutyryl, 2,2-dimethyl-3-tetrahydroquinolyloxypropionyl, 5-tetrahydroquinolyloxypentanoyl, 6-tetrahydroquinolyloxyhexanoyl, 2-(1-methyltetrahydroquinolyloxy)acetyl, 2-(2-oxotetrahydroquinolyloxy)acetyl, 3-(2-ethyltetrahydroquinolyloxy)propionyl, 2-(3-propyltetrahydroquinolyloxy)propionyl, 4-(4-butyltetrahydroquinolyloxy)butyryl, 2,2-dimethyl-3-(5-pentyltetrahydroquinolyloxy)propionyl, 5-(6-hexyltetrahydroquinolyloxy)pentanoyl, 6-(7-methyltetrahydroquinolyloxy)hexanoyl, 2-(8-methyltetrahydroquinolyloxy)acetyl, 2-(1,4-dimethyltetrahydroquinolyloxy)acetyl, 2-(2,4,6-trimethyltetrahydroquinolyloxy)acetyl, 2-(1-methyl-2-oxotetrahydroquinolyloxy)acetyl, 3-(2-oxotetrahydroquinolyloxy)propionyl, 4-(2-oxotetrahydroquinolyloxy)butyryl, 5-(2-oxotetrahydroquinolyloxy)pentanoyl, 6-(2-oxotetrahydroquinolyloxy)hexanoyl, 2-(1,6-dimethyl-2-oxotetrahydroquinolyloxy)acetyl, and the like.

[0304] The tetrahydronaphthyloxy-lower alkanoyl group includes a tetrahydronaphthyloxyalkanoyl group wherein the alkanoyl group is a straight chain or branched chain alkanoyl group having 2 to 6 carbon atom, for example, 2-tetrahydronaphthyloxyacetyl, 3-tetrahydronaphthyloxypropionyl, 2-tetrahydronaphthyloxypropionyl, 4-tetrahydronaphthyloxybutyryl, 2,2-dimethyl-3-tetrahydronaphthyloxypropionyl, 5-tetrahydronaphthyloxypentanoyl, 6-tetrahydronaphthyloxyhexanoyl, and the like.

[0305] The phenyl-lower alkenylcarbonyl group includes a phenylalkenylcarbonyl group wherein the alkenylcarbonyl moiety is a straight chain or branched chain alkenylcarbonyl group having 3 to 6 carbon atoms in the alkenyl moiety, for example cinnamoyl, 3-phenyl-2-propenylcarbonyl, 3-phenyl-1-propenylcarbonyl, 4-phenyl-3-butenylcarbonyl, 4-phenyl-2-butenylcarbonyl, 4-phenyl-1-butenylcarbonyl, 5-phenyl-4-pentenylcarbonyl, 5-phenyl-3-pentenylcarbonyl, 5-phenyl-2-pentenylcarbonyl, 5-phenyl-1-pentenylcarbonyl, 1-methyl-3-phenyl-2-butenylcarbonyl, 1-methylcinnamoyl, and the like.

[0306] The cycloalkenyl group includes a cycloalkenyl group having 3 to 8 carbon atoms, for example, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, and the like.

[0307] The phenyl-lower alkylaminocarbonyl group includes a phenylalkylaminocarbonyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, benzylaminocarbonyl, (2-phenylethyl)aminocarbonyl, (1-phenylethyl)aminocarbonyl, (3-phenylpropyl)aminocarbonyl, (4-phenylbutyl)aminocarbonyl, (5-phenylpentyl)aminocarbonyl, (6-phenylhexyl)aminocarbonyl, (1,1-dimethyl-2-phenylethyl)aminocarbonyl, (2-methyl-3-phenylpropyl)aminocarbonyl, and the like.

[0308] The 5- to 11-membered, saturated or unsaturated heteromonocyclic or heterobicyclic group containing 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom includes, for example, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, pyridyl, homopiperazinyl, 1,2,5,6-tetrahydropyridyl, thienyl, quinolyl, 1,4-dihydroquinolyl, benzothiazolyl, pyrazyl, pyrimidyl, pyridazyl, pyrrolyl, carbostyril, 3,4-dihydrocarbostyril, 1,2,3,4-tetrahydroquinolyl, indolyl, isoindolyl, indolinyl, benzimidazolyl, benzoxazolyl, imidazolidinyl, isoquinolyl, quinazolidinyl, 1,2,3,4-tetrahydroquinolyl, 1,2-dihydroisoquinolyl, quinoxalinyl, cinnolinyl, phthalazinyl, 1,2,3,4-tetrazolyl, 1,2,4-triazolyl, chromanyl, isoindolinyl, isochromanyl, pyrazolyl, imidazolyl, pyrazolidinyl, imidazo[1,2-a]pyridyl, benzofuryl, 2,3-dihydrobenzo[b]furyl, benzothienyl, 1-azacycloheptyl, 4H-chromenyl, 1H-indazolyl, isoindolinyl, 2-imidazolinyl, 2-pyrrolinyl, furyl, oxazolyl, isooxazolyl, thiazolyl, isothiazolyl, pyranyl, pyrazolidinyl, 2-pyrazolinyl, quinuclidinyl, 1,4-benzoxazinyl, 3,4-dihydro-2H-1,4-benzoxazinyl, 3,4-dihydro-2H-1,4-benzothiazinyl, 1,4-benzothiadinyl, 1,2,3,4-tetrahydroquinoxalinyl, 1,3-dithia-2,4-dihydronaphthalenyl, tetrahydro-1,3-oxazinyl, tetrahydrooxazolyl, 1,4-dithianaphthalenyl, and the like.

[0309] The above-mentioned heterocyclic group having 1 to 3 substituents selected from a lower alkyl group, a phenyl group, a lower alkanoyl group, a halogen atom, a phenyl-lower alkyl group and an oxo group includes the above-mentioned heterocyclic groups having 1 to 3 substituents selected from a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, a phenyl group, a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, a halogen atom, a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms and an oxo group, for example, 1-oxo-1,2,3,4-tetrahydroisoquinolyl, 2-oxopiperidinyl, 2-oxo-1-azabicycloheptyl, 2-oxopyrrolidinyl, 5-phenylthiazolyl, 1-methylimidazolyl, 1-propylimidazolyl, 4-methylimidazolyl, 4-phenylimidazolyl, 1,4-dimethylpyrrolyl, 4-methylpiperazinyl, 4-phenylpiperidinyl, 4-methylthiazolyl, 2-oxothiazolyl, 5-ethylthiazolyl, 4-phenylthiazolyl, 4-propylthiazolyl, 5-butylthiazolyl, 4-pentylthiazolyl, 2-hexylthiazolyl, 4,5-dimethylthiazolyl, 5-phenyl-4-methylthiazolyl, 1-ethylimidazolyl, 4-propylimidazolyl, 5-butylimidazolyl, 1-pentylimidazolyl, 1-hexylimidazolyl, 1,4-dimethylimidazolyl, 1,4,5-trimethylimidazolyl, 1-phenylimidazolyl, 2-phenylimidazolyl, 5-phenylimidazolyl, 1-methyl-4-phenylimidazolyl, 3-methyl-1,2,4-triazolyl, 5-ethyl-1,2,4-triazolyl, 3-phenyl-1,2,4-triazolyl, 2-oxo-1-methylimidazolyl, 2-oxoimidazolyl, 2-ethylpyrrolyl, 3-propylpyrrolyl, 5-butylpyrrolyl, 4-pentylpyrrolyl, 2-hexylpyrrolyl, 2,4,5-trimethylpyrrolyl, 2-phenylpyrrolyl, 2,5-diphenylpyrrolyl, 2-methyl-5-phenylpyrrolyl, 2-oxopyrrolyl, 1-methyl-1,2,3,4-tetrazolyl, 1-phenyl-1,2,3,4-tetrazolyl, 1-ethyl-1,2,3,4-tetrazolyl, 1-propyl-1,2,3,4-tetrazolyl, 1-butyl-1,2,3,4-tetrazolyl, 1-pentyl-1,2,3,4-tetrazolyl, 1-hexyl-1,2,3,4-tetrazolyl, 1-phenyl-1,2,3,4-tetrazolyl, 2-methylpyridyl, 3-ethylpyridyl, 4-propylpyridyl, 2-butylpyridyl, 3-pentylpyridyl, 4-hexylpyridyl, 2-phenylpyridyl, 3-phenylpyridyl, 4-phenylpyridyl, 2,4-dimethylpyridyl, 2,4,6-trimethylpyridyl, 2-methyl-4-phenylpyridyl, 2,4-diphenylpyridyl, 2,4,6-triphenylpyridyl, 2-oxopyridyl, 4-oxopyridyl, 4-methyl-2-oxopyridyl, 2-phenyl-4-oxopyridyl, 3-methylimidazo[1,2-a]pyridyl, 4-ethylimidazo[1,2-a]pyridyl, 3-phenylimidazo[1,2-a]pyridyl, 5-phenylimidazo[1,2-a]-pyridyl, 3-methyl-1H-indazolyl, 3-phenyl-1H-indazolyl, 1-methyl-1,2,3,4-tetrahydroisoquinolyl, 5-ethyl-1,2,3,4-tetrahydroisoquinoly, 6-phenyl-1,2,3,4-tetrahydroisoquinolyl, 1-oxo-6-methyl-1,2,3,4-tetrahydroisoquinolyl, 1-oxo-7-phenyl-1,2,3,4-tetrahydroisoquinolyl, 3,4-dimethylpiperazinyl, 3-ethylpyrrolidinyl, 2-propylpyrrolidinyl, 1-methylpyrrolidinyl, 3,4,5-trimethylpiperidinyl, 4-butylpiperidinyl, 4-pentylmorpholino, 4-hexylpiperazinyl, 4-butylpiperidinyl, 3-pentylmorpholino, 4-hexylpiperazinyl, 3-methylthiomorpholino, 4-phenylpiperazinyl, 3-phenylpyrrolidinyl, 2-oxo-4-methylpiperidinyl, 2-oxo-3-methylpyrrolidinyl, 2-oxo-4-phenylpiperidinyl, 4-methyl-1-azabicycloheptyl, 5-phenyl-1-azacycloheptyl, 6-methyl-2-oxo-1-azacycloheptyl, 1-methyl-2-oxoimidazolidinyl, 1-isobutyl-2-oxoimidazolidinyl, 1-benzyl-2-oxoimidazolidinyl, 2-oxotetrahydro-1,3-oxazinyl, 3-phenyl-2-oxo-1-azacycloheptyl, 2-oxotetrahydrooxazolyl, 3-chloropyridyl, 4-methylpiperazinyl, 4-isobutylpiperazinyl, 4-methylhomopiperazinyl, 4-acetylpiperazinyl, 4-benzylpiperazinyl, 4-ethylhomopiperazinyl, and the like.

[0310] The cyano-substituted lower alkyl group includes a cyanoalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, cyanomethyl, 2-cyanoethyl, 1-cyanoethyl, 3-cyanopropyl, 4-cyanobutyl, 5-cyanopentyl, 6-cyanohexyl, 1,1-dimethyl-2-cyanoethyl, 2-methyl-3-cyanopropyl, and the like.

[0311] The tetrazolyl-substituted lower alkyl group includes a tetrazolylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, tetrazolylmethyl, 2-tetrazolylethyl, 1-tetrazolylethyl, 3-tetrazolylpropyl, 4-tetrazolylbutyl, 5-tetrazolylpentyl, 6-tetrazolylhexyl, 1,1-dimethyl-2-tetrazolylethyl, 2-methyl-3-tetrazolylpropyl, and the like.

[0312] The lower alkanoyloxy-substituted lower alkyl group includes a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, which is substituted by a straight chain or branched chain alkanoyloxy group having 2 to 6 carbon atoms, for example, acetyoxymethyl, 2-propionyloxyethyl, 1-butyryloxyethyl, 3-acetyloxypropyl, 4-acetyloxybutyl, 4-isobutyryloxybutyl, 5-pentanoyloxypentyl, 6-acetyloxyhexyl, 6-tert-butylcarbonyloxyhexyl, 1,1-dimethyl-2-hexanoyloxyethyl, 2-methyl-3-acetyloxypropyl, and the like.

[0313] The amino group having optionally a lower alkanoyl substituent includes an amino group having optionally a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, amino, formylamino, acetylamino, propionylamino, butyrylamino, isobutyrylamino, pentanoylamino, tert-butylcarbonylamino, hexanoylamino, and the like.

[0314] The pyridyl-lower alkyl group includes a pyridylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, (4-pyridyl)methyl, 1-(3-pyridyl)ethyl, 2-(2-pyridyl)ethyl, 3-(2-pyridyl)propyl, 4-(3-pyridyl)butyl, 5-(4-pyridyl)pentyl, 6-(2-pyridyl)hexyl, 1,1-dimethyl-2-(3-pyridyl)ethyl, 2-methyl-3-(4-pyridyl)propyl, and the like.

[0315] The phenoxy-lower alkoxycarbonyl group includes a phenoxyalkoxycarbonyl group wherein the alkoxycarbonyl moiety is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, phenoxymethoxycarbonyl, 2-phenoxyethoxycarbonyl, 1-phenoxyethoxycarbonyl, 3-phenoxypropoxycarbonyl, 4-phenoxybutoxycarbonyl, 5-phenoxypentyloxycarbonyl, 6-phenoxyhexyloxycarbonyl, 1,1-dimethyl-2-phenoxyethoxycarbonyl, 2-methyl-3-phenoxypropoxycarbonyl, and the like.

[0316] The pyridyl-lower alkoxycarbonyl group includes a pyridylalkoxycarbonyl group wherein the alkoxycarbonyl group is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, (4-pyridyl)methoxycarbonyl, (2-pyridyl)methoxycarbonyl, (3-pyridyl)methoxycarbonyl, 2-(2-pyridyl)ethoxycarbonyl, 1-(1-pyridyl)ethoxycarbonyl, 3-(3-pyridyl)propoxycarbonyl, 4-(4-pyridyl)butoxycarbonyl, 5-(3-pyridyl)pentyloxycarbonyl, 6-(2-pyridyl)hexyloxycarbonyl, 1,1-dimethyl-2-(4-pyridyl)ethoxycarbonyl, 2-methyl-3-(3-pyridyl)propoxycarbonyl, and the like.

[0317] The fluorenyl-lower alkoxycarbonyl group includes a fluorenylalkoxycarbonyl group wherein the alkoxycarbonyl moiety is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, for example, (5-fluorenyl)methoxycarbonyl, 2-(2-fluorenyl)ethoxycarbonyl, 1-(1-fluorenyl)ethoxycarbonyl, 3-(3-fluorenyl)propoxycarbonyl, 4-(4-fluorenyl)butoxycarbonyl, 5-(5-fluorenyl)pentyloxycarbonyl, 6-(1-fluorenyl)hexyloxycarbonyl, 1,1-dimethyl-2-(2-fluorenyl)ethoxycarbonyl, 2-methyl-3-(3-fluorenyl)propoxycarbonyl, and the like.

[0318] The lower alkenyloxycarbonyl group includes an alkenyloxycarbonyl group wherein the alkenyloxycarbonyl moiety is a straight chain or branched chain alkenyloxycarbonyl group having 2 to 6 carbon atoms in the alkenyloxy moiety, for example, vinyloxycarbonyl, allyloxycarbonyl, 2-butenyloxycarbonyl, 3-butenyloxycarbonyl, 1-methylallyloxycarbonyl, 2-pentenyloxycarbonyl, 2-hexenyloxycarbonyl.

[0319] The piperidinyl-lower alkoxycarbonyl group having optionally a substituent selected from a lower alkanoyl group, a lower alkoxycarbonyl group and a lower alkyl group on the piperidine ring includes a piperidinylalkoxycarbonyl group wherein the alkoxycarbonyl group is a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety, which may have optionally 1 to 3 substituents selected from a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, a straight chain or branched chain alkoxycarbonyl group having 1 to 6 carbon atoms in the alkoxy moiety and a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, (4-piperidinyl)methoxycarbonyl, 2-(3-piperidinyl)ethoxycarbonyl, 1-(2-piperidinyl)ethoxycarbonyl, 3-(1-piperidinyl)propoxycarbonyl, 4-(4-piperidinyl)butoxycarbonyl, 5-(3-piperidinyl)pentyloxycarbonyl, 6-(2-piperidinyl)hexyloxycarbonyl, 1,1-dimethyl-2-(4-piperidinyl)ethoxycarbonyl, 2-methyl-3-(1-piperidinyl)propoxycarbonyl, (1-ethyl-4-piperidinyl)methoxycarbonyl, (1-t-butoxycarbonyl-4-piperidinyl)methoxycarbonyl, (1-acetyl-4-piperidinyl)methoxycarbonyl, 2-(1-methyl-4-piperidinyl)ethoxycarbonyl, 1-(4-propyl-2-piperidinyl)ethoxycarbonyl, 3-(4-butyl-3-piperidinyl)propoxycarbonyl, 4-(3-pentyl-2-piperidinyl)butoxycarbonyl, 5-(1-hexyl-4-piperidinyl) pentyloxycarbonyl, (1,2-dimethyl-4-piperidinyl)methoxycarbonyl, (3,4,5-trimethyl-1-piperidinyl)methoxycarbonyl, 2-(1-methoxycarbonyl-4-piperidinyl)ethoxycarbonyl, 1-(1-ethoxycarbonyl-4-piperidinyl)ethoxycarbonyl, 3-(4-propoxycarbonyl-1-piperidinyl)propoxycarbonyl, 4-(3-pentyloxycarbonyl-2-piperidinyl)butoxycarbonyl, 5-(1-hexyloxycarbonyl-4-piperidinyl)pentyloxycarbonyl, 6-(4-methoxycarbonyl-1-piperidinyl)hexyoxycarbonyl, 2-(2-acetyl-1-piperidinyl)ethoxycarbonyl, 1-(3-propionyl-2-piperidinyl)ethoxycarbonyl, 3-(4-butyryl-3-piperidinyl)propoxycarbonyl, 4-(4-pentanoyl-1-piperidinyl)butoxycarbonyl, 5-(1-hexanoyl-4-piperidinyl)pentyloxycarbonyl, 6-(1-acetyl-2-methyl-4-piperidinyl)hexyoxycarbonyl, (1-ethoxycarbonyl-2,6-dimethyl-4-piperidinyl)methoxycarbonyl, and the like.

[0320] The aminosulfonyloxy group having optionally a lower alkyl substituent includes an aminosulfonyloxy group having optionally 1 to 2 straight chain or branched chain alkyl substituents having 1 to 6 carbon atoms, for example, aminosulfonyloxy, methylaminosulfonyloxy, ethylaminosulfonyloxy, propylaminosulfonyloxy, isopropylaminosulfonyloxy, butylaminosulfonyloxy, tert-butylaminosulfonyloxy, pentylaminosulfonyloxy, hexylaminosulfonyloxy, dimethylaminosulfonyloxy, diethylaminosulfonyloxy, dipropylaminosulfonyloxy, dibutylaminosulfonyloxy, dipentylaminosulfonyloxy, dihexylaminosulfonyloxy, N-methyl-N-ethylaminosulfonyloxy, N-ethyl-N-propylaminosulfonyloxy, N-methyl-N-butylaminosulfonyloxy, N-methyl-N-hexylaminosulfonyloxy, and the like.

[0321] The phenyl-lower alkyl group includes a phenylalkyl group wherein the alkyl moiety is a straight chain or branched chain alkyl group having 1 to 6 carbon atoms, for example, benzyl, 2-phenylethyl, 1-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 1,1-dimethyl-2-phenylethyl, 5-phenylpentyl, 6-phenylhexyl, 2-methyl-3-phenylpropyl, and the like.

[0322] The lower alkanoyl-substituted amino group includes an amino group substituted by a straight chain or branched chain alkanoyl group having 1 to 6 carbon atoms, for example, formylamino, acetylamino, propionylamino, butyrylamino, isobutyrylamino, pentanoylamino, tert-butycarbonylamino, hexanoylamino, and the like.

[0323] The benzoheterocyclic derivatives of the present invention can be prepared by the following processes.

[0324] wherein G, R1, R2, R3, R and X are the same as defined above.

[0325] The process of Reaction Scheme-1 is carried out by reacting a benzoheterocyclic compound [2] and a carboxylic acid compound [3] by the conventional amido bond producing reaction. The amido bond producing reaction can be carried out under the conditions for the conventional amido bond producing reaction, for example,

[0326] (a) a mixed acid anhydride process, i.e. a process of reacting the carboxylic acid compound [3] with an alkyl carbonate to form a mixed acid anhydride and reacting the resultant with the amine compound [2],

[0327] (b) an activated ester process, i.e. a process of converting the carboxylic acid compound [3] into an activated ester such as p-nitrophenyl ester, N-hydroxysuccinimide ester, 1-hydroxybenzotriazole ester, etc., and reacting the resultant with the amine compound [2],

[0328] (c) a carbodiimide process, i.e. a process of condensing the carboxylic acid compound [3] and the amine compound [2] in the presence of an activating agent such as dicyclohexylcarbodiimide, carbonyldiimidazole, etc.,

[0329] (d) other processes, i.e. a process of converting the carboxylic acid compound [3] into a carboxylic anhydride by treating it with a dehydrating agent such as acetic anhydride, and reacting the resultant with the amine compound [2]; a process of reacting an ester of the carboxylic acid compound [3] with a lower alcohol and the amine compound [2] at a high temperature under high pressure; a process of reacting an acid halide compound of the carboxylic acid compound [3], i.e. a carboxylic acid halide, with the amine compound [2], and the like.

[0330] The mixed acid anhydride used in the above mixed acid anhydride process (a) is obtained by the known Schotten-Baumann reaction, and the reaction product is used without isolating from the reaction mixture for the reaction with the amine compound [2] to give the desired compound [1] of the present invention. The above Schotten-Baumann reaction is usually carried out in the presence of a basic compound. The basic compound is any conventional compounds used in the Schotten-Baumann reaction and includes, for example, organic basic compounds such as triethylamine, trimethylamine, pyridine, dimethylaniline, 1-methyl-2-pyrrolidine (NMP), N-methylmorpholine, 1,5-diazabicyclo[4.3.0]nonene-5 (DBN), 1,8-diazabicyclo[5.4.0]undecene-7 (DBU), 1,4-diazabicyclo[2.2.2]octane (DABCO), and inorganic basic compounds such as potassium carbonate, sodium carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, etc. The reaction is usually carried out at a temperature from about −20° C. to about 100° C., preferably at a temperature from 0° C. to about 50° C., for about 5 minutes to about 10 hours, preferably for 5 minutes to about 2 hours.

[0331] The reaction between the mixed acid anhydride thus obtained and the amine compound [2] is usually carried out at a temperature from −20° C. to about 150° C., preferably at a temperature from 10° C. to about 50° C., for 5 minutes to about 10 hours, preferably for 5 minutes to about 5 hours. The mixed acid anhydride process is usually carried out in a solvent. The solvent may be any conventional solvents which are usually used in the mixed acid anhydride process and includes, for example, halogenated hydrocarbons (e.g. chloroform, dichloromethane, dichloroethane, etc.), aromatic hydrocarbons (e.g. benzene, p-chlorobenzene, toluene, xylene, etc.), ethers (e.g. diethyl ether, diisopropyl ether, tetrahydrofuran, dimethoxyethane, etc.), esters (e.g. methyl acetate, ethyl acetate, etc.), aprotic polar solvents (e.g. N,N-dimethylformamide, dimethylsulfoxide, acetonitrile, hexamethylphosphoric triamide, etc.), or a mixture of these solvents. The alkyl halocarbonate used in the mixed acid anhydride process includes, for example, methyl chloroformate, methyl bromoformate, ethyl chloroformate, ethyl bromoformate, isobutyl chloroformate, and the like. In said process, the carboxylic acid compound [3], the alkyl halocarbonate and the amine compound [2] are usually used in each equimolar amount, but preferably, the alkyl halocarbonate and the carboxylic acid compound [3] are used each in an amount of about 1 to 1.5 mole to 1 mole of the amine compound [2].

[0332] Among the above other processes (d), in case of the process of reacting the carboxylic acid halide with the amine compound [2], the reaction is usually carried out in the presence of a basic compound in an appropriate solvent. The basic compound is any conventional compounds and includes, for example, in addition to the basic compounds used in the above Schötten-Baumann reaction, sodium hydroxide, potassium hydroxide, sodium hydride, potassium hydride, and the like. The solvent includes, for example, in addition to the solvents used in the mixed acid anhydride process, alcohols (e.g. methanol, ethanol, propanol, butanol, 3-methoxy-1-butanol, ethylcellosolve, methylcellosolve, etc.), pyridine, acetone, water, and the like. The amount of the amine compound [2] and the carboxylic acid halide is not critical, but the carboxylic acid halide is usually used at least in equimolar amount, preferably about in an amount of 1 mole to 5 moles to 1 mole of the amine compound [2]. The reaction is usually carried out at a temperature from about −20° C. to about 180° C., preferably at a temperature from 0° C. to about 150° C., for about 5 minutes to about 30 hours.

[0333] The amido bond producing reaction in above Reaction Scheme-1 may also be carried out by reacting the carboxylic acid compound [3] and the amine compound [2] in the presence of a condensing agent such as phosphorus compounds (e.g. phenylphosphine-2,2′-dithiodipyridine, diphenylphosphinyl chloride, phenyl-N-phenylphosphoramide chloridate, diethyl chlorophosphate, diethyl cyanophosphate, diphenylphosphoric azide, bis(2-oxo-3-oxazolidinyl)phosphinic chloride, etc.).

[0334] The reaction is usually carried out in the presence of the solvent and the basic compound as used in the above reaction of the carboxylic acid halide and the amine compound [2] at a temperature from −20° C. to 150° C., preferably at a temperature from 0° C. to about 100° C., for about 5 minutes to about 30 hours. The condensing agent and the carboxylic acid compound [3] are used at least in an equimolar amount, preferably in an amount of about 1 to 2 moles, to 1 mole of the amine compound [2].

[0335] wherein G, p, R1, R2, R3, R8 and X are the same as defined above, R10a is a hydrogen atom, a lower alkyl group or a lower alkanoyl group having optionally a halogen substituent, R11a is a lower alkanoyl group having optionally a substituent selected from a halogen atom and a hydroxy group, a phenoxy-lower alkanoyl group having optionally a substituent selected from a lower alkyl group, a phenyl group, a lower alkoxy group, a halogen-substituted lower alkyl group, an amino group having optionally a lower alkyl substituent, a nitro group, a lower alkanoyl-substituted amino group and a halogen atom, wherein the alkanoyl moiety may optionally be substituted by a halogen atom, a lower alkoxy-substituted lower alkanoyl group, a lower alkanoyloxy-substituted lower alkanoyl group, a group of the formula:

[0336] a phenoxy-lower alkoxycarbonyl group, a quinolylcarbonyl group, a quinolyloxy-substituted lower alkanoyl group, a tetrahydroquinolyloxy-substituted lower alkanoyl group having optionally a substituent selected from a lower alkyl group and an oxo group on the quinoline ring, a pyridyl-lower alkoxycarbonyl group, a fluorenyl-lower alkoxycarbonyl group, a lower alkenyloxycarbonyl group, a tetrahydronaphthyloxy-substituted lower alkanoyl group, a piperidinyl-lower alkoxycarbonyl group having optionally a substituent selected from a lower alkanoyl group, a lower alkoxycarbonyl group and a lower alkyl group on the piperidine ring, a lower alkoxycarbonyl group having optionally a halogen substituent, a benzofurylcarbonyl group, a benzimidazolylcarbonyl group, a tetrahydroisoquinolylcarbonyl group, a phenyl-lower alkoxycarbonyl group or a phenyl-lower alkenylcarbonyl group, R11b is a lower alkyl group, a cycloalkyl group, a phenyl-lower alkyl group having optionally a substituent selected from a lower alkyl group and a halogen atom on the phenyl ring, wherein the alkyl moiety may optionally be substituted by a hydroxy group, a phenoxy-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, an aminocarbonyl group having optionally a substituent selected from a lower alkyl group, a pyridyl-lower alkyl group and a phenyl-lower alkyl group, a benzoyl-lower alkyl group or a lower alkylsulfonyl group, X1 is a halogen atom, M is an alkali metal such as sodium, potassium, etc., and R15 is a lower alkyl group, a pyridyl-lower alkyl group or a phenyl-lower alkyl group.

[0337] The reaction of the compound [4] and the compound [5] is carried out in the same conditions as in the reaction of the compound [2] and the compound [3] in above Reaction Scheme-1.

[0338] The reaction of the compound [4] and the compound [6a] is usually carried out in the presence or absence of a basic compound in an appropriate inert solvent. The inert solvent includes, for example, aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), ethers (e.g. tetrahydrofuran, dioxane, diethylene glycol dimethyl ether, etc.), halogenated hydrocarbons (e.g. dichloromethane, chloroform, carbon tetrachloride, etc.), lower alcohols (e.g. methanol, ethanol, isopropanol, butanol, t-butanol, etc.), acetic acid, ethyl acetate, acetone, acetonitrile, pyridine, dimethylsulfoxide, dimethylformamide, hexamethylphosphoric triamide, or a mixture of these solvents. The basic compound includes, for example, carbonates or hydrogen carbonates of alkali metal (e.g. sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, etc.), metal hydroxides (e.g. sodium hydroxide, potassium hydroxide, etc.), sodium hydride, potassium, sodium, sodium amide, metal alcoholates (e.g. sodium methylate, sodium ethylate, etc.), or organic basic compounds such as pyridine, N-ethyldiisopropylamine, dimethylaminopyridine, triethylamine, 1,5-diazabicyclo[4.3.0]nonene-5 (DBN), 1,8-diazabicyclo[5.4.0]undecene-7 (DBU), 1,4-diazabicyclo[2.2.2]octane (DABCO). The amount of the compound [4] and the compound [6a] is not critical, but the compound [6a] is usually used at least in an equimolar amount, preferably in an amount of 1 to 10 moles, to 1 mole of the compound [4]. The reaction is usually carried out at a temperature from 0° C. to about 200° C., preferably at a temperature from 0° C. to about 170° C., for 30 minutes to about 75 hours. There may be added an alkali metal halide such as sodium iodide, potassium iodide, copper powder, etc. into the reaction system.

[0339] The reaction of the compound [4] and the compound [6b] is carried out under the same condition as in the reaction of the compound [1t] and the compound [18] in the following Reaction Scheme-9.

[0340] The reaction of the compound [4] and the compound [7] is carried out in the presence of an acid in an appropriate solvent. The acid includes, for example, organic acids (e.g. acetic acid, trifluoroacetic acid, etc.), or inorganic acids (e.g. hydrochloric acid, sulfuric acid, etc.). The solvent may be the same solvents as those used in the reaction of the carboxylic acid halide and the amine compound [2] in above Reaction Scheme-1. The compound [71 is used at least in an equimolar amount, preferably in an amount of 1 to 3 moles, to 1 mole of the compound [4]. The reaction is carried out at a temperature from 0° C. to about 150° C., preferably at a temperature from room temperature to about 100° C., for 10 minutes to about 5 hours.

[0341] The reaction of the compound [4] and the compound [8] is carried out in the presence or absence of a basic compound, preferably in the absence of a basic compound, in an appropriate solvent or without a solvent. The solvent and the basic compound used therein are the same ones as those used in the reaction of the carboxylic acid halide and the amine compound [2] in above Reaction Scheme-1.

[0342] The compound [8] is usually used at least in an amount of 1 to 5 moles, preferably in an amount of 1 to 3 moles, to 1 mole of the compound [4]. The reaction is usually carried out at a temperature from 0° C. to about 200° C., preferably at a temperature from room temperature to 150° C., for 5 minutes to about 30 hours. There may be added a boron compound such as boron trifluoride ethyl ether, etc. into the reaction system.

[0343] wherein R1 and R are the same as defined above, Ga is a group of the formula:

[0344] or a group of the formula:

[0345] Gb is a group of the formula:

[0346] or a group of the formula:

[0347] Gc is a group of the formula:

[0348] or a group of the formula:

[0349] and X, Y, R4 and R5 are the same as defined above.

[0350] The reaction of converting the compound [1e] into the compound [1f] is carried out by reduction. The reduction reaction is carried out by using a hydrogenating agent. The hydrogenating agent includes, for example, lithium aluminum hydride, lithium borohydride, sodium borohydride, diboran, etc., and is used at least in an equimolar amount, preferably in an amount of 1 to 15 moles, to 1 mole of the starting compound. The reduction reaction is usually carried out in an appropriate solvent such as water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), ethers (e.g. tetrahydrofuran, diethyl ether, diisopropyl ether, diglyme, etc.), or a mixture of these solvents. The reduction is usually carried out at a temperature from about −60° C. to 150° C., preferably at a temperature from −30° C. to 100° C., for about 10 minutes to 15 hours. When lithium aluminum hydride or diboran is used as a reducing agent, the reaction is preferably carried out in an anhydrous solvent such as tetrahydrofuran, diethyl ether, diisopropyl ether, diglyme, etc.

[0351] The reaction of converting the compound [1e] into the compound [1g] is carried out in an appropriate solvent or without a solvent in the presence or absence of a dehydrating agent. The solvent includes, for example, alcohols (e.g. methanol, ethanol, isopropanol, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), halogenated hydrocarbons (e.g. dichloromethane, dichloroethane, chloroform, carbon tetrachloride, etc.), aprotic polar solvents (e.g. dimethylformamide, dimethylacetamide, N-methylpyrrolidone, etc.), or a mixture of these solvents. The dehydrating agent includes, for example, drying agents which are conventionally used for drying solvents (e.g. molecular sieves, etc.), mineral acids (e.g. hydrochloric acid, sulfuric acid, boron trifluoride, etc.), organic acids (e.g. p-toluenesulfonic acid, acetic acid, etc.). The reaction is usually carried out at a temperature from room temperature to 250° C., preferably at a temperature from about 50° C. to about 200° C., for one to about 48 hours. The amount of the compound [9] is not critical, but it is used at least in an equimolar amount, preferably in an amount of 1 mole to excess amount, to 1 mole of the compound [1e]. The dehydrating agent is used in an excess amount when a drying agent is used, and when an acid is used as a dehydrating agent, it is used in a catalytic amount.

[0352] The subsequent reduction is carried out by various reduction reactions, for example, by catalytic hydrogenation in the presence of a catalyst in an appropriate solvent. The solvent includes, for example, water, acetic acid, alcohols (e.g. methanol, ethanol, isopropanol, etc.), hydrocarbons (e.g. hexane, cyclohexane, etc.), ethers (e.g. diethylene glycol dimethyl ether, dioxane, tetrahydrofuran, diethyl ether, etc.), esters (e.g. ethyl acetate, methyl acetate, etc.), aprotic polar solvents (e.g. dimethylformamide, etc.), or a mixture of these solvents. The catalyst is, for example, palladium, palladium-black, palladium-carbon, platinum, platinum oxide, copper chromite, Raney nickel, and the like. The catalyst is usually used in an amount of 0.02 to 1 mole to 1 mole of the starting compound. The reaction is usually carried out at a temperature from 20° C. to about 100° C., preferably at a temperature from 0° C. to about 70° C., under a pressure of 1 atm to 10 atms of hydrogen, for 0.5 hour to about 20 hours.

[0353] The above mentioned conditions for the reduction can be employed in the present reduction, but the reduction using a hydrogenating agent is more preferable. The hydrogenating agent includes, for example, lithium aluminum hydride, sodium borohydride, sodium cyanoborohydride, diboran, etc., and is used at least in an amount of 0.1 mole, preferably in an amount of 0.1 mole to 10 moles, to 1 mole of the compound [1e]. The reduction is carried out in an appropriate solvent such as water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), ethers (e.g. tetrahydrofuran, diethyl ether, diglyme, etc.), dimethylformamide, or a mixture of these solvents, at a temperature from about −60° C. to about 50° C., preferably at a temperature from −30° C. to room temperature, for about 10 minutes to about 5 hours. When lithium aluminum hydride or diboran is used as a reducing agent, an anhydrous solvent such as diethyl ether, tetrahydrofuran, diglyme, etc., is preferably used.

[0354] wherein R1, R and X1 are the same as defined above, R5a is a lower alkyl group having optionally a hydroxy substituent, R16 and R17 are each a hydrogen atom or a lower alkyl group, R5b is a benzoyl group having optionally a halogen substituent on the phenyl ring, Gd is a group of the formula:

[0355] or a group of the formula:

[0356] Ge is a group of the formula:

[0357] or a group of the formula:

[0358] Gf is a group of the formula:

[0359] or a group of the formula:

[0360] R3a is a hydrogen atom or a hydroxy-substituted lower alkyl group, and X, Y, R4, R5a and R5b are the same as defined above.

[0361] The reaction of the compound [1h] and the compound [10] is carried out under the same conditions as those in the reaction of the compound [4] and the compound [6] in above Reaction Scheme-2.

[0362] The reaction of the compound (1h] and the compound [11] is carried out in the presence of a reducing agent in an appropriate solvent or without a solvent. The solvent includes, for example, water, alcohols (e.g. methanol, ethanol, isopropanol, etc.), acetonitrile, formic acid, acetic acid, ethers (e.g. dioxane, diethyl ether, diglyme, tetrahydrofuran, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), or a mixture thereof. The reducing agent includes, for example, formic acid, ammonium formate, alkali metal salts of fatty acids (e.g. sodium formate, etc.), hydrogenating agents (e.g. sodium borohydride, sodium cyanoborohydride, lithium aluminum hydride, etc.), catalysts (e.g. palladium-black, palladium-carbon, platinum oxide, platinum-black, Raney nickel, etc.), and the like.

[0363] When formic acid is used as a reducing agent, the reaction is usually carried out at a temperature from room temperature to about 200° C., preferably at a temperature from about 50° C. to about 150° C., for about one to about 10 hours. Formic acid is used in an excess amount to the compound [1h].

[0364] When a hydrogenating agent is used, the reaction is usually carried out at a temperature from about −30° C. to about 100° C., preferably at a temperature from about 0° C. to about 70° C., for about 30 minutes to about 12 hours. The hydrogenating agent is used in an amount of 1 mole to 20 moles, preferably in an amount of 1 mole to 6 moles, to 1 mole of the compound [1h]. Especially, when lithium aluminum hydride is used as a reducing agent, the solvent is preferably ethers (e.g. diethyl ether, dioxane, tetrahydrofuran, diglyme, etc.) or aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.).

[0365] Moreover, when a catalyst is used, the reaction is usually carried out under atmospheric pressure to 20 atms of hydrogen, preferably, under atmospheric pressure to 10 atms of hydrogen, or in the presence of a hydrogen donor such as formic acid, ammonium formate, cyclohexene, hydrazine hydrate, etc., at a temperature from −30° C. to 100° C., preferably at a temperature from 0° C. to 60° C., for about one to 12 hours. The catalyst is usually used in an amount of 0.1 to 40% by weight, preferably in an amount of 1 to 20% by weight to the amount of the compound [1h]. The hydrogen donor is usually used in an excess amount to the compound [1h].

[0366] The compound [11] is usually used at least in an equimolar amount, preferably in an amount of 1 mole to excess amount, to 1 mole of the compound [1h].

[0367] The reaction of the compound [11] and the compound [12] is carried out under the same conditions as those of the reaction of the compound [2] and the compound [3] in above Reaction Scheme-1.

[0368] wherein R1, R and X1 are the same as defined above, R18 is an amino-substituted lower alkanoyl group having optionally a lower alkyl substituent, a lower alkyl group, a lower alkoxycarbonyl-substituted lower alkyl group, a carboxy-substituted lower alkyl group or a group of the formula: —ACONR6R7 (A, R6 and R7 are the same as defined above), Gg is a group of the formula:

[0369] or a group of the formula:

[0370] Gh is a group of the formula:

[0371] or a group of the formula:

[0372] X, Y and R3a are the same as defined above, R18′ is an amino-substituted lower alkanoyloxy group having optionally a lower alkyl substituent, a lower alkoxy group, a lower alkoxycarbonyl-substituted lower alkoxy group, a carboxy-substituted lower alkoxy group or a group of the formula: —O—ACONR6R7 (A, R6 and R7 are the same as defined above).

[0373] The reaction of the compound [1k] and the compound [13] is carried out under the same conditions as those in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2.

[0374] wherein R1, R, X1 and Ga are the same as defined above, Gi is a group of the formula:

[0375] or a group of the formula:

[0376] X and Y are the same as defined above, R19 is a lower alkoxy group, R20 is a hydrogen atom, a lower alkoxycarbonyl group, a lower alkoxy group or a phenyl group, D is a lower alkylene group, n is 0 or 1, and R21 is a phenyl group.

[0377] The reaction of the compound [1e] and the compound [14] or the compound [15] is carried out in the presence of a basic compound in an appropriate solvent. The basic compound includes, for example, inorganic bases (e.g. sodium, potassium, sodium hydride, sodium amide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, etc.), organic bases such as alkali metal alcoholates (e.g. sodium methylate, sodium ethylate, potassium t-butoxide, etc.), an alkyl lithium, aryl lithium or lithium amide (e.g. methyl lithium, n-butyl lithium, phenyl lithium, lithium diisopropyl amide, etc.), pyridine, piperidine, quinoline, triethylamine, N,N-dimethylaniline, and the like. The solvent may be any solvent which does not affect the reaction, for example, ethers (e.g. diethyl ether, dioxane, tetrahydrofuran, monoglyme, diglyme, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), hydrocarbons (e.g. n-hexane, heptane, cyclohexane, etc.), amines (e.g. pyridine, N,N-dimethylaniline, etc.), aprotic polar solvents (e.g. N,N-dimethylformamide, dimethylsulfoxide, hexamethylphosphoric triamide, etc.), alcohols (e.g. methanol, ethanol, isopropanol, etc.), and the like. The reaction is usually carried out at a temperature from −80° C. to 150° C., preferably at a temperature from −80° C. to about 120° C., for 0.5 to about 15 hours.

[0378] wherein R1 and R are the same as defined above, Gj is a group of the formula:

[0379] or a group of the formula:

[0380] Gk is a group of the formula:

[0381] or a group of the formula:

[0382] Gl is a group of the formula:

[0383] or a group of the formula:

[0384] X, Y and D are the same as defined above, and R20a is a lower alkoxycarbonyl group.

[0385] The reaction of converting the compound [1n] into the compound [1o] is carried out under the same conditions as those in the reduction reaction of converting the compound [1e] into the compound [1g] in above Reaction Scheme-3. When a hydrogenating agent is used in said reduction reaction, there may preferably be added a metal halide such as a nickel chloride into the reaction system.

[0386] The compound [1n] may be also converted into the compound [1o] by reducing the compound [1n] with metal magnesium-methanol. The reaction is usually carried out at a temperature from 0° C. to 50° C., preferably at a temperature from 0° C. to room temperature, for one to about 10 hours. Metal magnesium is usually used in an amount of 1 to 10 moles, preferably in an amount of 1 to 7 moles, to 1 mole of the compound [1n]. When the compound [1n] wherein X is a methylene group is used in this reaction, there may be obtained the compound [1o] wherein X is a methylene group and the compound [1o] wherein X is a group of the formula: ═CH—, but these compounds [1o] are easily separated.

[0387] The reaction of converting the compound [1o] into the compound [1p] is carried out in the presence or absence of an acid or a basic compound in an appropriate solvent or without a solvent. The solvent includes, for example, water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), ketones (e.g. acetone, methyl ethyl ketone, etc.), ethers (e.g. dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, etc.), fatty acids (e.g. acetic acid, formic acid, etc.), or a mixture of these solvents. The acid includes, for example, mineral acids (e.g. hydrochloric acid, sulfuric acid, hydrobromic acid, etc.) and organic acids (e.g. formic acid, acetic acid, aromatic sulfonic acid, etc.). The basic compounds includes, for example, metal carbonates (e.g. sodium carbonate, potassium carbonate, etc.), metal hydroxides (e.g. sodium hydroxide, potassium hydroxide, calcium hydroxide, lithium hydroxide, etc.), and the like. The reaction is usually carried out at a temperature from room temperature to 200° C., preferably at a temperature from room temperature to 150° C., for 10 minutes to about 25 hours.

[0388] The compound [1p] is also prepared by treating the compound [1o] in an appropriate solvent in the presence of a dialkyl sulfide-Lewis acid such as dimethyl sulfide-aluminum chloride. The solvent may be the same solvents for the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2. The reaction is usually carried out at a temperature from 0° C. to 70° C., preferably at a temperature from 0° C. to 50° C., for one to 10 hours.

[0389] wherein R1 and R are the same as defined above, Gm is a group of the formula:

[0390] or a group of the formula:

[0391] Gn is a group of the formula:

[0392] or a group of the formula:

[0393] R22 is a carboxy-substituted lower alkyl group, and R3a, R6, R7, A, X and Y are the same as defined above.

[0394] The reaction of the compound [1q] and the compound [16] is carried out under the same conditions as those in the reaction of the compound [2] and the compound [3] in above Reaction Scheme-1.

[0395] wherein G, p, R1, R8, X1, A, m and R13 are the same as defined above, R9a is a benzoyl group having optionally a lower alkyl substituent on the phenyl ring, a phenyl-lower alkanoyl group having optionally a lower alkyl substituent on the phenyl ring or a benzoyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, and R12a is a lower alkanoyl group.

[0396] The reaction of converting the compound [1s] into the compound [1t] is carried out under the same conditions as those in the reaction of converting the compound [1e] into the compound [1f] in above Reaction Scheme-3.

[0397] The reaction of the compound [1t] and the compound [17] is carried out under the same conditions as those in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2.

[0398] The reaction of the compound [1t] and the compound [18] is carried out in the presence or absence of a basic compound in an appropriate solvent or without a solvent. The solvent includes, for example, the above-mentioned aromatic hydrocarbons, lower alcohols (e.g. methanol, ethanol, propanol, etc.), dimethyl formamide, dimethyl sulfoxide, halogenated hydrocarbons (e.g. chloroform, methylene chloride, etc.), acetone, pyridine, and the like. The basic compound includes, for example, organic bases (e.g. triethylamine, pyridine, etc.), sodium hydroxide, potassium hydroxide, sodium hydride, and the like. The reaction is also carried out in the presence of a mineral acid (e.g. sulfuric acid, etc.) in a solvent such as acetic acid.

[0399] The compound [18] is used in an amount of 1 mole to excess amount, to 1 mole of the starting compound. The reaction is usually carried out at a temperature from 0° C. to about 200° C., preferably at a temperature from 0° C. to about 150° C., for 0.5 hour to about 20 hours.

[0400] The starting compound [2a] can be prepared by the processes as illustrated by the following Reaction Scheme.

[0401] wherein G, p, R1 and R8 are the same as defined above.

[0402] The reaction of the compound [2] and the compound [19] is carried out under the same conditions as those in the reaction of the compound [2] and the compound [3] in above Reaction Scheme-1.

[0403] The reaction of converting the compound [20] into the compound [4] is carried out by (i) subjecting the compound [20] to reduction reaction by using a catalyst in an appropriate solvent, or (ii) subjecting the compound [20] to reduction reaction by using a mixture of a metal or a metal salt with an acid, a metal or a metal salt with an alkali metal hydroxide, a sulfide, an ammonium salt in an appropriate inert solvent.

[0404] When (i) a catalyst is used, the solvent includes, for example, water, acetic acid, alcohols (e.g. methanol, ethanol, isopropanol, etc.), hydrocarbons (e.g. hexane, cyclohexane, etc.), ethers (e.g. dioxane, tetrahydrofuran, diethyl ether, diethylene glycol dimethyl ether, etc.), esters (e.g. ethyl acetate, methyl acetate, etc.), aprotic polar solvents (e.g. N,N-dimethylformamide, etc.), or a mixture of these solvents. The catalyst includes, for example, palladium, palladium-black, palladium-carbon, platinum, platinum oxide, copper chromite, Raney nickel, and the like. The catalyst is used in an amount of 0.02 to 1 mole, to 1 mole of the starting compound. The reaction is usually carried out at a temperature from −20° C. to 150° C., preferably at a temperature from 0° C. to about 100° C., under a pressure of 1 to 10 atms of hydrogen, for 0.5 hour to 10 hours. There may be added an acid such as hydrochloric acid into the reaction system.

[0405] When the method (ii) is employed, there is used as a reducing agent a mixture of iron, zinc, tin or stannous chloride and a mineral acid (e.g. hydrochloric acid, sulfuric acid, etc.), or a mixture of iron, iron sulfide, zinc or tin and an alkali metal hydroxide (e.g. sodium hydroxide, etc.), a sulfide (e.g. ammonium sulfide, etc.), aqueous ammonia, an ammonium salt (e.g. ammonium chloride, etc.). The inert solvent includes, for example, water, acetic acid, methanol, ethanol, dioxane, and the like. The conditions for the above reduction can be selected according to the kinds of the reducing agent to be used. For example, when a mixture of stannous chloride and hydrochloric acid is used as a reducing agent, the reaction is preferably carried out at a temperature from 0° C. to about 80° C., for 0.5 hour to about 10 hours. The reducing agent may be used at least in an equimolar amount, usually in an amount of 1 to 5 moles, to 1 mole of the starting compound.

[0406] The starting compound [3] is prepared by the processes as illustrated by the following Reaction Schemes.

[0407] wherein p, R8, D and X1 are the same as defined above, R24 is a phenyl-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, X2 is a halogen atom, R23 is a lower alkoxycarbonyl group, R25 is a phenoxy group having optionally a lower alkyl substituent on the phenyl ring, R26 is a phenyl group having optionally a lower alkyl substituent on the phenyl ring, R27 is a phenyl-lower alkyl group having optionally a substituent selected from a halogen atom, a lower alkoxycarbonyl group and an aminocarbonyl group having optionally a substituent selected from a lower alkyl group and an amino-substituted lower alkyl group having optionally a lower alkyl substituent, or a benzoyl-lower alkyl group having optionally a halogen substituent on the phenyl ring.

[0408] The reaction of the compound [21] and the compound [22] and the reaction of the compound [24] and the compound [27] are carried out in the presence of zinc and a catalyst in an appropriate solvent. The solvent includes, for example, ethers (e.g. 1,2-dimethoxyethane, diethyl ether, tetrahydrofuran, dioxane, etc.), acetonitrile, dimethylformamide, and the like. The catalyst includes, for example, palladium compounds or nickel compounds such as tetrakistriphenylphosphine palladium [Pd(PPh3)4], palladium acetate [Pd(OCOCH3)2], palladium chloride [PdCl2], bistriphenylphosphinenickel dichloride [Ni(PPh3)2Cl2], and the like. The reaction is usually carried out at a temperature from 0° C. to 70° C., preferably at a temperature from 0° C. to about 50° C., for 1 hour to about 80 hours.

[0409] The compound [24] or the compound [27] is used at least in an equimolar amount, preferably in an amount of 1 to 2 moles, to 1 mole of the compound [21] or the compound [22], respectively. The catalyst is usually used in an amount of 0.01 to about 1 mole, preferably in an amount of 0.03 to about 0.3 mole, to 1 mole of the starting compound.

[0410] The reaction of the compound [24] and the compound [25] and the reaction of the compound [29] and the compound [30] are carried out under the same conditions as those in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2.

[0411] The reaction of converting the compound [23], [26], [28] or [31] into the compound [3a], [3b], [3c] or [3d], respectively, is carried out under the same conditions as those in the reaction of converting the compound [1o] into the compound [1p] in above Reaction Scheme-7.

[0412] wherein R28 and R29 are each a lower alkyl group, R30 is a phenyl group having optionally a lower alkyl substituent on the phenyl ring, and p, R8 and X2 are the same as defined above.

[0413] The reaction of the compound [32] and the compound [33] is carried out in an appropriate solvent. The solvent may be any solvents used in Grignard reaction, but preferably ethers (e.g. diethyl ether, dioxane, tetrahydrofuran, etc.), aromatic hydrocarbons (e.g. benzene, toluene, etc.), saturated hydrocarbons (e.g. pentane, hexane, heptane, cyclohexane, etc.), and the like. The compound [33] is usually used at least in an equimolar amount, preferably in an amount of 1 to 2 moles, to 1 mole of the compound [32]. The reaction is usually carried out at a temperature from −70° C. to 50° C., preferably at a temperature from −30° C. to room temperature, for 1 to about 50 hours.

[0414] The reaction of converting the compound [34] into the compound [35] is carried out in the presence of an oxidizing agent in an appropriate solvent. The oxidizing agent includes, for example, chromic acid pyridinium salts (e.g. pyridinium chlorochromate, pyridinium dichlorochromate, etc.), dimethyl sulfoxide-oxazolyl chloride, dichromic acid, dichromates (e.g. sodium dichromate, potassium dichromate, etc.), permanganic acid, permanganates (e.g. potassium permanganate, sodium permanganate, etc.), manganese dioxide, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), and the like. The solvent used in the reaction with an oxidizing agent includes, for example, water, organic acids (e.g. formic acid, acetic acid, trifluoroacetic acid, etc.), alcohols (e.g. methanol, ethanol, etc.), halogenated hydrocarbons (e.g. chloroform, dichloromethane, etc.), ethers (e.g. tetrahydrofuran, diethyl ether, dioxane, etc.), dimethylsulfoxide, dimethylformamide, or a mixture of these solvents. The oxidizing agent is usually used at least in an equimolar amount, preferably in an amount of 1 mole to 25 moles, to 1 mole of the starting compound. The reaction is usually carried out at a temperature from about 0° C. to about 100° C., preferably at a temperature from 0° C. to about 70° C., for 1 hour to about 7 hours.

[0415] The reaction of converting the compound [35] into the compound [3e] is carried out by subjecting the compound [35] to alkylation in the presence of an alkylating agent in an appropriate solvent, followed by subjecting the product to hydrolysis, or by subjecting directly the compound [35] to hydrolysis.

[0416] In the alkylation of the compound [35], the alkylating agent used therein includes, for example, an alkyl halide such as methyl iodide, etc. The alkylation reaction is usually carried out at a temperature from room temperature to about 200° C., preferably at a temperature from room temperature to about 150° C., for 1 hour to about 30 hours. The solvent includes, for example, ethers (e.g. dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, diethyl ether, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), halogenated hydrocarbons (e.g. dichloromethane, chloroform, carbon tetrachloride, etc.), lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), polar solvents (e.g. dimethylsulfoxide, dimethylformamide, hexamethylphosphoric triamide, acetone, acetonitrile, nitromethane, etc.), and the like. The alkylating agent is usually used in an equimolar amount, preferably in an amount of 1 to 8 moles, to 1 mole of the compound [35].

[0417] The subsequent hydrolysis may be carried out by a conventional method, for example, by in the presence of a basic compound (e.g. sodium carbonate, potassium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide, barium hydroxide, etc.), or a mineral acid (e.g. hydrochloric acid, sulfuric acid, etc.), or an organic acid (e.g. acetic acid, etc.), in a solvent such as water, alcohols (e.g. methanol, ethanol, isopropanol, etc.), ketones (e.g. acetone, methyl ethyl ketone, etc.), ethers (e.g. dioxane, ethylene glycol dimethyl ether, etc.), acetic acid, or a mixture of these solvents. The reaction is usually carried out at a temperature from room temperature to 200° C., preferably at a temperature from room temperature to 150° C., for 0.5 hour to 20 hours.

[0418] In the reaction of subjecting directly the compound [35] to hydrolysis, the reaction is carried out under the same conditions as those in the above hydrolysis. The reaction is carried out for 1 hour to 30 hours.

[0419] The compound [3e] is also prepared by subjecting the compound [35] to hydrolysis in the presence of a mineral acid (e.g. sulfuric acid, hydrochloric acid, nitric acid, etc.), or in the presence of an organic acid (e.g. acetic acid, aromatic sulfonic acid, etc.) under the same conditions such as solvents, reaction temperature, reaction period, as those in the above hydrolysis reaction.

[0420] The starting compound [32] is prepared by the processes as illustrated in the following Reaction Scheme.

[0421] wherein p, R8, X2, R28, R29 and X2 are the same as defined above.

[0422] The reaction of the compound [36] and the compound [37] is carried out under the same conditions as those in the reaction of the compound [2] and the compound [3] in above Reaction Scheme-1 wherein a carboxylic acid halide is used. The compound [37] is used at least in an equimolar amount, preferably in an amount of 1 to 2 moles, to 1 mole of the compound [36].

[0423] The reaction of the compound [38] and the compound [39] is carried out in a solvent such as ethers (e.g. diethyl ether, tetrahydrofuran, dioxane, monoglyme, diglyme, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), aliphatic hydrocarbons (e.g. n-hexane, heptane, cyclohexane, etc.), at a temperature from 0° C. to 150° C., preferably at a temperature from 0° C. to about 100° C., for 0.5 hour to about 5 hours. The compound [39] is used at least in an equimolar amount, preferably in an amount of 1 to 1.5 mole, to 1 mole of the compound [38].

[0424] wherein p, R8, R23, R21 and X1 are the same as defined above, and R31 is a phenyl group having optionally a halogen substituent.

[0425] The reaction of the compound [39A] and the compound [40] is carried out under the same conditions as those in the reaction of the compound [1e] and the compound [14] or the compound [15] in above Reaction Scheme-6.

[0426] The reaction of converting the compound [41] into the compound [3f] is carried out under the same conditions as those in the reaction of converting the compound [10] into the compound [1p] in above Reaction Scheme-6.

[0427] wherein p, R8 and R23 are the same as defined above, R32 is a lower alkylsulfonyloxy group having optionally a halogen substituent, or a halogen atom, and R33 is a phenyl group having optionally a substituent selected from a lower alkyl group, a lower alkoxy group, a phenyl-lower alkoxy group, a nitro group, an amino group having optionally a lower alkanoyl substituent, a hydroxy group, a lower alkanoyloxy group, a halogen-substituted lower alkoxy group, a phenyl group and an amino-substituted lower alkoxy group having optionally a lower alkyl substituent.

[0428] The reaction of the compound [42] and the compound [43] is carried out in an appropriate solvent in the presence or absence of a lithium compound such as lithium chloride, etc., in the presence of a basic compound and a catalyst. The solvent may be the same solvents as those used in the reaction of the compound [38] and the compound [39] in above Reaction Scheme-13. The basic compound may be the same basic compounds as those used in the reaction of the compound [2] and the compound [3] in above Reaction Scheme-1 wherein a carboxylic acid halide is used. The catalyst includes, for example, tetrakis(triphenylphosphine)palladium, palladium chloride, and the like. The reaction is usually carried out at a temperature from room temperature to 200° C., preferably at a temperature from room temperature to about 150° C., for one to about 10 hours. The basic compound and the lithium compound are each used at least in an equimolar amount, preferably in an amount of 1 to 2 moles, to 1 mole of the compound [42]. The catalyst is used in a catalytic amount.

[0429] The reaction of converting the compound [44] into the compound [3g] is carried out under the same conditions as those in the reaction of converting the compound [1o] into the compound [1p] in above Reaction Scheme-7.

[0430] wherein G, p, R1, R8 and R10a are the same as defined above, R11c is a phenyl-lower alkyl group having optionally a substituent selected from a lower alkyl group and a halogen atom on the phenyl ring, and having optionally a hydroxy substituent on the alkyl moiety, a benzoyl-lower alkyl group, or a phenoxy-lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, R11d is in addition to the groups for R11c, a phenyl group having optionally a substituent selected from a lower alkyl group and a halogen atom.

[0431] The reaction of the compound [4] and the compound [45] is carried out in the presence of a dialkyl azodicarboxylate (e.g. diethyl azodicarboxylate, dibutyl diazodicarboxylate, etc.), a dialkyl azodicarboxyamide (e.g. 1,1′-azodicarbonyldi(piperidine), etc.), and a phosphorus compound (e.g. a trialkylphosphine, a triarylphosphine, etc.). The solvent includes, for example, ethers (e.g. tetrahydrofuran, 1,2-dimethoxyethane, diethyl ether, diisopropyl ether, diglyme, etc.), aromatic hydrocarbons (e.g. benzene, toluene, etc.), or a mixture of these solvents. The dialkyl azodicarboxylate, the phosphorus compound and the compound [45] are each used at least in an equimolar amount, preferably in an amount of 1 to 3 moles, to 1 mole of the compound [4]. The reaction is usually carried out at a temperature from −20° C. to 100° C., preferably at a temperature from −20° C. to 50° C., for 1 hour to 30 hours.

[0432] The compound [1v] wherein R10a is a lower alkanoyl group having optionally a halogen substituent may be converted into the corresponding compound [1w] by subjecting the compound [1v] to hydrolysis. The hydrolysis is carried out under the same conditions as those in the hydrolysis of the compound [1] wherein R9 is a phenyl group having at least one lower alkanoyloxy substituent on the phenyl ring.

[0433] The reaction of the compound [4] and the compound [46] is carried out under the same conditions as those in the reaction of converting the compound [1e] into the compound [1g] in above Reaction Scheme-3. The compound [46] is used at least in an equimolar amount, preferably in an amount of 1 to 3 moles, to 1 mole of the compound [4].

[0434] wherein G, p, R1, R8, X1 and X2 are the same as defined above.

[0435] The reaction of the compound [4a] and the compound [47] is carried out under the same conditions as those in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2.

[0436] wherein G, p, R1, R8 and X1 are the same as defined above, and R34 is a lower alkyl group, a lower alkanoyl group, a phenyl-lower alkyl group having optionally a substituent selected from a halogen atom, a lower alkoxycarbonyl group, an aminocarbonyl group having optionally a substituent selected from a lower alkyl group and an amino-substituted lower alkyl group having optionally a lower alkyl substituent on the phenyl ring, or a pyrrolidinyl-substituted lower alkyl group.

[0437] The reaction of the compound [48] and the compound [49] is carried out under the same conditions as those in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2.

[0438] wherein G, p, R1 and R8 are the same as defined above, and R35 is an anilino group having optionally a lower alkyl substituent on the phenyl ring.

[0439] The reaction of the compound [1A] and the compound [50] is carried out under the same conditions as those in the reaction of converting the compound [1e] into the compound [1g] in above Reaction Scheme-3. The compound [50] is used at least in an equimolar amount, preferably in an amount of 1 to 5 moles, to 1 mole of the compound [1A].

[0440] wherein R36 is a lower alkoxy group or a halogen atom, R37 is a lower alkyl group, R8, R28, R29, R9 and X2 are the same as defined above, and q is 0 or 1.

[0441] The reaction of the compound [51] and the compound [52] is carried out under the same conditions as those in the reaction of the compound [32] and the compound [33] in above Reaction Scheme-12. The compound [52] is used at least in an equimolar amount, preferably in an amount of 1 to 2 moles, to 1 mole of the compound [51].

[0442] wherein R8, p, R32 and R23 are the same as defined above, R38 is a lower alkyl group, a lower alkoxy group, a phenyl-lower alkoxy group, a hydroxy group, a lower alkanoyloxy group, a halogen-substituted lower alkoxy group, a nitro group, an amino group having optionally a lower alkanoyl substituent, a phenyl group, or an amino-substituted lower alkoxy group having optionally a lower alkyl substituent, and r is 0, 1 or 2.

[0443] The reaction of the compound [54] and the compound [55] is carried out under the same conditions as those in the reaction of the compound [42] and the compound [43] in above Reaction Scheme-15.

[0444] The reaction of converting the compound [56] into the compound [3i] is carried out under the same conditions as those in the reaction of converting the compound [44] into the compound [3g] in above Reaction Scheme-15.

[0445] wherein R28, R29, R8, p, X1 and X2 are the same as defined above, s is an integer of 0 to 5, and R39′ is a lower alkyl group.

[0446] The reaction of the compound [32] and the compound [57] is carried out under the same conditions as those in the reaction of the compound [32] and the compound [33] in above Reaction Scheme-12.

[0447] The reaction of the compound [58] and the compound [59] is carried out under the same conditions as those in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2.

[0448] The reaction of the compound [38] and the compound [57] is carried out under the same conditions as those in the reaction of the compound [1e] and the compound [14] or the compound [15] in above Reaction Scheme-6. The compound [57] is used at least in an equimolar amount, preferably in an amount of 1 to 1.5 mole, to 1 mole of the compound [38].

[0449] The reaction of converting the compound [58] or the compound [60] into the compound [3j] is carried out under the same conditions as those in the reaction of converting the compound [1o] into the compound [1p] in above Reaction Scheme-7, except the reaction is carried out for 1 hour to about 50 hours.

[0450] The reaction of converting the compound [3j] into the compound [3k] is carried out under the same conditions as those in the reaction of converting the compound [1e] into the compound [1g] in above Reaction Scheme-3.

[0451] wherein R8, p and X2 are the same as defined above, R49 is a cyano group, a lower alkoxycarbonyl group or a carboxy group, R39 is a lower alkyl group, a phenyl group, a lower alkanoyl group, a halogen atom, a phenyl lower alkyl group, or an oxo group, and t is an integer of 0 to 3, and the group of the formula:

[0452] is a 5- to 11-membered, saturated or unsaturated heteromonocyclic or heterobicyclic group containing 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom.

[0453] The reaction of the compound [61] and the compound [62] is carried out under the same conditions as those in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2.

[0454] When the compound [63] is a compound of the formula [63] wherein R49 is a cyano group or a lower alkoxycarbonyl group, the reaction of converting the compound [63] into the compound [3k] is carried out under the same conditions as those in the reaction of converting the compound [1o] into the compound [1p] in above Reaction Scheme-7.

[0455] wherein G, R1, R8, p and R10a are the same as defined above, R11e is a lower alkanoyl group having a halogen substituent, R40 is a phenyl group having optionally a substituent selected from a lower alkyl group, a phenyl group, a lower alkoxy group, a halogen-substituted lower alkyl group, an amino group having optionally a lower alkyl substituent, a lower alkanoyl-substituted amino group, a nitro group and a halogen atom, a lower alkyl group, a lower alkanoyl group, a quinolyl group, a tetrahydroquinolyl group having optionally a substituent selected from a lower alkyl group and an oxo group on the quinoline ring, or a tetrahydronaphthyl group, R11f is a phenoxy-lower alkanoyl group having optionally a substituent selected from a lower alkyl group, a phenyl group, a lower alkoxy group, a halogen-substituted lower alkyl group, an amino group having optionally a lower alkyl substituent, a lower alkanoyl-substituted amino group, a nitro group and a halogen atom on the phenyl ring, a lower alkoxy-substituted lower alkanoyl group, a lower alkanoyloxy-substituted lower alkanoyl group, a quinolyloxy-substituted lower alkanoyl group, a tetrahydroquinolyloxy-substituted lower alkanoyl group having optionally a substituent selected from a lower alkyl group and an oxo group on the quinoline ring, or a tetrahydronaphthyloxy-substituted lower alkanoyl group.

[0456] The reaction of the compound [1C] and the compound [63] is carried out under the same conditions as those in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2.

[0457] The compound [1D] wherein R11f is a lower alkanoyloxy-substituted lower alkanoyl group is reacted under the same conditions as those in the reaction of converting the compound [1o] into the compound [1p] in above Reaction Scheme-7 to give the compound [1D] wherein the corresponding R11f is a lower alkanoyl group having a hydroxy substituent.

[0458] wherein R1, G, R8, p and R10a are the same as defined above, and R49 is a tetrahydroisoquinolyl group or a group of the formula:

[0459] The reaction of converting the compound [4] into the compound [1E] is carried out by (i) reacting the compound [4] with a carbonylating agent in the presence of a basic compound in an appropriate solvent, followed by (ii) reacting the resulting product with the compound [65] in the presence of a basic compound in an appropriate solvent.

[0460] The solvent and the basic compound used in the above process (i) may be each the same ones as those used in the reaction of reacting a carboxylic acid halide with the amine compound [2] in above Reaction Scheme-1. The carbonylating agent includes, for example, carbonyldiimidazole, phosgene, diphosgene, urea, triphosgene, etc. The carbonylating agent is usually used in an amount of 0.05 to 1 mole, preferably in an amount of 0.1 to 1 mole, to 1 mole of the compound [4]. The reaction is usually carried out at a temperature from 0° C. to 200° C., preferably at a temperature from 0° C. to about 180° C., for 1 hour to about 10 hours.

[0461] The solvent and the basic compound used in the above process (ii) may be each the same ones as those used in the process (i). The processes (i) and (ii) are carried out in one-pot system. The compound [65] is used in an amount of 1 to 5 moles, preferably in an amount of 1 to 3 moles, to 1 mole of the compound [4]. The reaction is usually carried out at a temperature from room temperature to 150° C., preferably at a temperature from room temperature to about 120° C., for 0.5 hour to about 5 hours.

[0462] wherein R1, R2, R3, R and X1 are the same as defined above, and RA′ is the same groups as those for RA other than a hydrogen atom.

[0463] The reaction of the compound [1F] and the compound [66] is carried out under the same conditions as those in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2.

[0464] wherein R1, G, R8, p and X1 are the same as defined above.

[0465] The reaction of converting the compound [1H] into the compound [1I] is carried out under the same conditions as those in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2.

[0466] wherein R1, G, R8, p and R10a are the same as defined above, R44 is a lower alkyl group having optionally a halogen substituent, a phenoxy-lower alkyl group, a phenyl-lower alkyl group, a pyridyl-lower alkyl group, a fluorenyl-lower alkyl group, a lower alkenyl group or a piperidinyl-lower alkyl group having optionally a substituent selected from a lower alkanoyl group, a lower alkoxycarbonyl group and a lower alkyl group on the piperidine ring.

[0467] The reaction of converting the compound [4] into the compound [67] is carried out under the same conditions as those in the reaction of converting the compound [4] into the compound [1E] in above Reaction Scheme-25.

[0468] wherein R1 and R are the same as defined above, Go is a group of the formula:

[0469] or a group of the formula:

[0470] Gp is a group of the formula:

[0471] or a group of the formula:

[0472] R3a, X and Y are the same as defined above, R45 is a cyano-substituted lower alkyl group, R46 is a tetrazolyl-substituted lower alkyl group, and M is an alkali metal such as sodium, potassium, etc.

[0473] The reaction of converting the compound [1K] into the compound [1L] is carried out by reacting the compound [1K] with the compound [68] in the presence of a basic compound in an appropriate solvent. The solvent includes, for example, halogenated hydrocarbons (e.g. chloroform, dichloromethane, dichloroethane, carbon tetrachloride, etc.), alcohols (e.g. methanol, ethanol, isopropanol, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), ethers (e.g. dioxane, diethylene glycol dimethyl ether, diethyl ether, tetrahydrofuran, etc.), polar solvents (e.g. dimethylformamide, dimethylacetamide, N-methylpyrrolidone, acetic anhydride, acetonitrile, dimethyl sulfoxide, hexamethylphosphoric triamide, etc.). The basic compound includes, for example, inorganic bases (e.g. sodium hydroxide, potassium hydroxide, sodium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, potassium carbonate, sodium methoxide, sodium ethoxide, sodium hydride, sodium, potassium, sodium amide, etc.), or organic bases (e.g. N,N-dimethylaniline, piperidine, pyridine, triethylamine, sodium acetate, potassium acetate, etc.). The compound [68] is used at least in an equimolar amount, preferably in an amount of 1 to 5 moles, to 1 mole of the compound [1K]. The reaction is usually carried out at a temperature from room temperature to 200° C., preferably at a temperature from 50° C. to about 150° C., for 1 hour to about 40 hours.

[0474] wherein R8, p, R9 and R23 are the same as defined above, R47 is a lower alkylsulfonyloxy group having optionally a halogen substituent, and R48 is a lower alkyl group.

[0475] The reaction of the compound [69], carbon monooxide [70] and the compound [71] is carried out in the presence of a catalyst and a basic compound in an appropriate solvent. The solvent and the basic compound used therein are the same ones as those used in the reaction of the compound [2] and the compound [3] in above Reaction Scheme-1 wherein a carboxylic acid halide is used. The catalyst includes, for example, palladium acetate, 1,3-bis(diphenylphosphino)propane (dppp), and the like. The reaction is usually carried out at a temperature from room temperature to 200° C., preferably at a temperature from room temperature to about 150° C., for 1 hour to about 10 hours. The compound [70], the compound [71] and the catalyst are each used in an excess amount to the compound [69].

[0476] wherein R50 is a 5- to 11-membered, saturated or unsaturated heteromonocyclic or heterobicyclic group containing 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom, and said heterocyclic group being optionally substituted by 1 to 3 groups selected from a lower alkyl group, a phenyl group, a lower alkanoyl group, a halogen atom, a phenyl-lower alkyl group and an oxo group, and R32, R23, R8, p, X1 and X2 are the same as defined above.

[0477] The reaction of the compound [72] and the compound [73] is carried out under the same conditions as in the reaction of the compound [54] and the compound [55] in above Reaction Scheme-21.

[0478] The reaction of converting the compound [74] into the compound [3m] is carried out under the same conditions as in the reaction of converting the compound [1o] into the compound [1p] in above Reaction Scheme-7.

[0479] The reaction of the compound [72] and the compound [75] is carried out under the same conditions as in the reaction of the compound [54] and the compound [55] in above Reaction Scheme-21.

[0480] The reaction of converting the compound [76] into the compound [3m] is carried out in the presence of a basic compound and an oxidizing agent in an appropriate solvent. The solvent and the oxidizing agent used therein are the same ones as those used in the reaction of converting the compound [34] into the compound [35] in above Reaction Scheme-12.

[0481] The basic compound includes, for example, sodium hydroxide, potassium hydroxide, sodium hydride, etc.

[0482] The oxidizing agent is used at least in an equimolar amount, preferably in an amount of 1 to 4 moles, to 1 mole of the compound [76].

[0483] The reaction is usually carried out at a temperature from 0° C. to about 150° C., preferably at a temperature from 0° C. to about 120° C., for about 1 hour to about 7 hours.

[0484] The reaction of the compound [77] and the compound [78] is carried out by treating the compound [77] with a basic compound in an appropriate solvent, at a temperature from −80° C. to 50° C., preferably at a temperature from −80° C. to room temperature, for 0.5 hour to 5 hours, and followed by reacting the product with the compound [78] in the presence of a zinc compound (e.g. zinc, zinc chloride, etc.), a catalyst and a basic compound in the same solvent.

[0485] The basic compound used for the treatment of the compound [77] includes an alkyl lithium, an aryl lithium, or a lithium amide, for example, methyl lithium, n-butyl lithium, phenyl lithium, lithium diisopropylamide, and the like. The basic compound is used at least in an quimolar amount, preferably in an amount of 1 to 2 moles, to 1 mole of the compound [77]. The solvent and the catalyst are the same as those in the reaction of the compound [21] and the compound [22] in above Reaction Scheme-11, and are used in the same amount as those in said reaction in above Reaction Scheme-11.

[0486] The reaction of the product derived from the compound [77] and the compound [78] is usually carried out at a temperature from 0° C. to 150° C., preferably at a temperature from 0° C. to 10° C., for 1 hour to about 10 hours.

[0487] The basic compound used in the reaction of the product derived from the compound [77] and the compound [78] includes, for example, in addition to diisopropylethylamine, the same basic compounds used in the reaction of a carboxylic acid halide of the compound [3] and the amine compound [2] in above Reaction Scheme-1.

[0488] The zinc compound and the basic compound used in the reaction of the product derived from the compound [77] and the compound [78] are used at least in an equimolar amount, preferably in an amount of 1 to 2 moles, to 1 mole of the compound [77].

[0489] The reaction of converting the compound [79] into the compound [74] is carried out by subjecting the compound [79] to catalytic hydrogenation in an appropriate solvent. The solvent includes, for example, water, acetic acid, alcohols (e.g. methanol, ethanol, isopropanol, etc.), hydrocarbons (e.g. hexane, cyclohexane, etc.), ethers (e.g. dioxane, tetrahydrofuran, diethyl ether, diethylene glycol dimethyl ether, etc.), esters (e.g. ethyl acetate, methyl acetate, etc.), aprotic polar solvents (e.g. N,N-dimethyl formamide, etc.), or a mixture of these solvents. The catalyst includes, for example, palladium, palladium-black, palladium-carbon, platinum, platinum oxide, copper chromite, Raney nickel, and the like. The catalyst is usually used in an amount of 0.02 to 1 mole, to 1 mole of the starting compound. The reaction is usually carried out at a temperature from −20° C. to about 150° C., preferably at a temperature from 0° C. to about 100° C., under 1 to 10 atms of hydrogen, for 0.5 hour to about 10 hours.

[0490] There may be added sodium acetate, etc. into the reaction system.

[0491] wherein R1, G, R8, p, X1, R39 and t are the same as defined above.

[0492] The reaction of the compound [80] and the compound [81] is carried our under the same conditions as in the reaction of the compound [4] and the compound [6a] in above Reaction Scheme-2.

[0493] wherein R1, G, R8 and p are the same as defined above, and R51 and R52 are each a lower alkyl group.

[0494] The reaction of the compound [4a] and the compound [82] is carried out in the presence of an acid in an appropriate solvent. The solvent includes, for example, water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), ketones (e.g. acetone, methyl ethyl ketone, etc.), ethers (e.g. dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, etc.), fatty acids (e.g. acetic acid, formic acid, etc.), or a mixture of these solvents. The acid includes, for example, mineral acids (e.g. hydrochloric acid, sulfuric acid, hydrobromic acid, etc.), organic acids (e.g. formic acid, acetic acid, aromatic sulfonic acid, etc.).

[0495] The reaction is usually carried out at a temperature from room temperature to about 200° C., preferably at a temperature from room temperature to about 150° C., for 0.5 hour to about 5 hours. The compound [82] is used at least in an equimolar amount, preferably in an mount of 1 to 2 moles, to 1 mole of the compound [4a].

[0496] The compound of the formula [1] wherein R1 is a hydroxy group can be prepared by subjecting the compound of the formula [1] wherein R1 is a lower alkoxy group to de-alkylation. The de-alkylation reaction is carried out in the presence of an acid in an appropriate solvent. The solvent includes, for example, water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), ethers (e.g. dioxane, tetrahydrofuran, etc.), halogenated hydrocarbons (e.g. dichloromethane, chloroform, carbon tetrachloride, etc.), polar solvents (e.g. acetonitrile, etc.), organic acids (e.g. acetic acid, etc.), or a mixture of these solvents. The acid includes, for example, mineral acids (e.g. hydrochloric acid, sulfuric acid, hydrobromic acid, etc.), Lewis acids (e.g. boron trifluoride, aluminum chloride, boron tribromide, etc.), iodides (e.g. sodium iodide, potassium iodide, etc.), and a mixture of a Lewis acid and a iodide. The reaction is usually carried out at a temperature from room temperature to 150° C., preferably at a temperature from room temperature to 120° C., for 0.5 hour to 15 hours.

[0497] The compound of the formula [1] wherein R9 is a phenyl group having at least one phenyl-lower alkoxy substituent on the phenyl ring is converted into the compound of the formula [1] wherein R9 is a phenyl group having at least one hydroxy substituent on the phenyl ring by subjecting it to catalytic reduction. The catalytic reduction is carried out in the presence of a reducing agent in an appropriate solvent. The solvent includes, for example, water, alcohols (e.g. methanol, ethanol, isopropanol, etc.), acetic acid, ethyl acetate, ethers (e.g. dioxane, tetrahydrofuran, diethyl ether, diglyme, etc.), aromatic hydrocarbons (e.g. benzene, toluene, xylene, etc.), or a mixture of these solvents. The reducing agent includes, for example, catalysts such as palladium-black, palladium-carbon, platinum oxide, platinum-black, platinum-carbon Raney nickel, etc. The reaction is usually carried out at a temperature from −30° to 100° C., preferably at a temperature from 0° C. to 60° C., under a pressure from atmospheric pressure to 10 atms of hydrogen. The catalyst is usually used in an amount of 0.1 to 40% by weight, preferably in an amount of 0.1 to 20% by weight, to the amount of the starting compound.

[0498] The compound of formula [1] wherein R9 is a phenyl group having at least one lower alkanoyloxy substituent on the phenyl ring, or a lower alkanoyloxy group can be converted into the compound of the formula [1] wherein R9 is a phenyl group having at least one hydroxy substituent on the phenyl ring or a hydroxy group, respectively, by subjecting them to hydrolysis. The hydrolysis is carried out in the presence of an acid or a basic compound in an appropriate solvent or without a solvent. The solvent includes, for example, water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), ketones (e.g. acetone, methyl ethyl ketone, etc.), ethers (e.g. dioxane, tetrahydrofuran, ethylene glycol dimethyl ether etc.), fatty acids (e.g. formic acid, acetic acid, etc.), or a mixture of these solvents. The acid includes, for example, mineral acids (e.g. hydrochloric acid, sulfuric acid, hydrobromic acid, etc.), organic acids (e.g. formic acid, acetic acid, aromatic sulfonic acids, etc.), and the like. The basic compound includes, for example, metal carbonates (e.g. sodium carbonate, potassium carbonate, etc.), metal hydroxides (e.g. lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, etc.), and the like. The reaction is usually carried out at a temperature from room temperature to about 200° C., preferably at a temperature from room temperature to about 150° C., for 0.5 to about 25 hours.

[0499] The compound of the formula [1] wherein R8 is a lower alkoxy group can be converted into the compound of the formula [1] wherein R8. is a hydroxy group by subjecting it to de-alkylation reaction. The compound [1] wherein R9 is a phenyl group having at least one lower alkoxy substituent on the phenyl ring can be converted into the compound of the formula [1] wherein R9 is a phenyl group having at least one hydroxy substituent on the phenyl ring by subjecting it to de-alkylation reaction. The de-alkylation reaction is carried out in the presence of an acid in an appropriate solvent. The solvent includes, for example, water, lower alcohols (e.g. methanol, ethanol, isopropanol, etc.), ethers (e.g. dioxane, tetrahydrofuran, etc.), halogenated hydrocarbons (e.g. dichloromethane, chloroform, carbon tetrachloride, etc.), polar solvents (e.g. acetonitrile, etc.), organic acids (e.g. acetic acid, etc.), or a mixture of these solvents. The acid includes, for example, mineral acids (e.g. hydrochloric acid, sulfuric acid, hydrobromic acid, etc.), Lewis acids (e.g. boron trifluoride, aluminum chloride, boron tribromide, etc.), iodides (e.g. sodium iodide, potassium iodide, etc.), and a mixture of a Lewis acid and a iodide. The reaction is usually carried out at a temperature from room temperature to 150° C., preferably at a temperature from room temperature to 120° C., for 0.5 hour to about 15 hours.

[0500] The compound of the formula [1] wherein R11 is a phenoxy-lower alkanoyl group having at least one amino substituent on the phenyl ring can be converted into the compound of the formula [1] wherein R11 is a phenoxy-lower alkanoyl group having at least one amino substituent having a lower alkyl substituent on the phenyl ring by reacting it with a compound of the formula: R41X1 [10a] (wherein R41 is a lower alkyl group and X1 is the same as defined above), or a compound of the formula: R16COR17 [11] (wherein R16 and R17 are the same as defined above) under the same conditions as those in the reaction of the compound [1h] and the compound [10] or the compound [11] in above Reaction Scheme-4.

[0501] The compound of the formula [1] wherein R9 is a 5- to 11-membered, saturated or unsaturated heteromonocyclic or heterobicyclic group containing 1 to 4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom wherein these heteroatoms may optionally be substituent, and said heterocyclic group has a secondary amino group on the heterocyclic nucleus, is reacted with a compound of the formula: R42X [10b] (wherein X is the same as defined above and R42 is a lower alkyl group, a phenyl-lower alkyl group or a lower alkanoyl group) or a group of the formula: R16COR17 [11] (wherein R16 and R17 are the same as defined above) under the same conditions as those in the reaction of the compound [1h] with the compound [10] or the compound [11] in above Reaction Scheme-4, to give the compound of the formula [1] wherein the corresponding R9 is the above heterocyclic group wherein the secondary amino group on the heterocyclic nucleus is substituted by a lower alkyl group, a phenyl-lower alkyl group or a lower alkanoyl group, or reacted with a compound of the formula: R43OH [12a] (wherein R43 is a lower alkanoyl group) under the same conditions as those in the reaction of the compound [2] with the compound [3] in above Reaction Scheme-1 to give the compound of the formula [1] wherein the corresponding R9 is a heterocyclic group wherein the secondary amino group on the heterocyclic nucleus is substituted by a lower alkanoyl group.

[0502] Among the desired compounds [1] of the present invention, the compounds having an acidic group can easily be converted into salts by treating with a pharmaceutically acceptable basic compound. The basic compound includes, for example, metal hydroxides (e.g. sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, etc.), alkali metal carbonates or hydrogen carbonates (e.g. sodium carbonate, sodium hydrogen carbonate, etc.) and alkali metal alcoholates (e.g. sodium methylate, potassium ethylate, etc.). Besides, among the desired compounds [1] of the present invention, the compounds having a basic group can easily be converted into acid addition salts thereof by treating with a pharmaceutically acceptable acid. The acid includes, for example, inorganic acids (e.g. sulfuric acid, nitric acid, hydrochloric acid, hydrobromic acid, etc.), and organic acids (e.g. acetic acid, p-toluenesulfonic acid, ethanesulfonic acid, oxalic acid, maleic acid, fumaric acid, citric acid, succinic acid, benzoic acid, etc.). These salts show as well excellent pharmacological activities as the desired compounds [1].

[0503] In addition, the compounds [1] of the present invention include stereoisomers and optical isomers, and these isomers are also useful as a vasopressin antagonist, vasopressin agonist or an oxytocin antagonist.

[0504] The compounds of the present invention thus obtained can easily be isolated and purified by conventional isolation methods. The isolation methods are, for example, distillation method, recrystallization method, column chromatography, ion exchange chromatography, gel chromatography, affinity chromatography, preparative thin layer chromatography, extraction with a solvent, and the like.

[0505] The desired compounds [1] of the present invention and salts thereof are useful as a vasopressin antagonist, vasopressin agonistic activities and an oxytocin antagonist, and are used in the form of a conventional pharmaceutical preparation. The preparation is prepared by using conventional diluents or carriers such as fillers, thickening agents, binders, wetting agent, disintegrators, surfactants, lubricants, and the like. The pharmaceutical preparations can be selected from various forms in accordance with the desired utilities, and the representative forms are tablets, pills, powders, solutions, suspensions, emulsions, granules, capsules, suppositories, injections (solutions, suspensions, etc.), and the like. In order to form in tablets, there are used carriers such as vehicles (e.g. lactose, white sugar, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, crystalline cellulose, silicic acid, etc.), binders (e.g. water, ethanol, propanol, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethyl cellulose, shellac, methyl cellulose, potassium phosphate, polyvinylpyrrolidone, etc.), disintegrators (e.g. dry starch, sodium alginate, agar powder, laminaran powder, sodium hydrogen carbonate, calcium carbonate, polyoxyethylene sorbitan fatty acid esters, sodium laurylsulfate, stearic monoglyceride, starches, lactose, etc.), disintegration inhibitors (e.g. white sugar, stearin, cacao butter, hydrogenated oils, etc.), absorption promoters (e.g. quaternary ammonium base, sodium laurylsulfate, etc.), wetting agents (e.g. glycerin, starches, etc.), adsorbents (e.g. starches, lactose, kaolin, bentonite, colloidal silicates, etc.), lubricants (e.g. purified talc, stearates, boric acid powder, polyethylene glycol, etc.), and the like. Moreover, the tablets may also be in the form of a conventional coated tablet, such as sugar-coated tablets, gelatin-coated tablets, enteric coated tablets, film coating tablets, or double or multiple layer tablets. In the preparation of pills, the carriers include vehicles (e.g. glucose, lactose, starches, cacao butter, hydrogenated vegetable oils, kaolin, talc, etc.), binders (e.g. gum arabic powder, tragacanth powder, gelatin, ethanol, etc.), disintegrators (e.g. laminaran, agar, etc.), and the like. In the preparation of suppositories, the carriers include, for example, polyethylene glycol, cacao butter, higher alcohols, higher alcohol esters, gelatin, semi-synthetic glycerides, and the like. Capsules can be prepared by charging a mixture of the compound of the present invention and the above carriers into hard gelatin capsules or soft capsules in usual manner. In the preparation of injections, the solutions, emulsions and suspensions are sterilized and are preferably made isotonic with the blood. In the preparation of these solutions, emulsions and suspensions, there are used conventional diluents, such as water, ethyl alcohol, macrogol, propylene glycol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, polyoxyethylene sorbitan fatty acid esters, and the like. In this case, the pharmaceutical preparations may also be incorporated with sodium chloride, glucose, or glycerin in an amount sufficient to make them isotonic, and may also be incorporated with conventional solubilizers, buffers, anesthetizing agents. Besides, the pharmaceutical preparations may optionally be incorporated with coloring agents, preservatives, perfumes, flavors, sweeting agents, and other medicaments, if required.

[0506] The amount of the desired compound of the present invention to be incorporated into the vasopressin antagonist, vasopressin agonist or the oxytocin antagonist is not specified but may be selected from a broad range, but usually, it is preferably in the range of 1 to 70% by weight, more preferably 5 to 50% by weight.

[0507] The vasopressin antagonist, the vasopressin agonist or the oxytocin antagonist containing as an active ingredient the compounds [1] of the present invention or a salt thereof may be administered in any method, and a suitable method for administration may be determined in accordance with various forms of preparations, ages, sexes and other conditions of the patients, the degree of severity of diseases, and the like. For example, tablets, pills, solutions, suspensions, emulsions, granules and capsules are administered orally. The injections are intravenously administered alone or together with a conventional auxiliary liquid (e.g. glucose, amino acid solutions), and further are optionally administered alone in intramuscular, intracutaneous, subcutaneous, or intraperitoneal route, if required. Suppositories are administered in intrarectal route.

[0508] The dosage of the vasopressin antagonist, the vasopressin agonist and the oxytocin antagonist of the present invention may be selected in accordance with the usage, ages, sexes and other conditions of the patients, the degree of severity of the diseases, and the like, but it is usually in the range of about 0.6 to 50 mg of the active compound of the present invention per 1 kg of body weight of the patient per day. The active compound is preferably contained in an amount of about 10 to about 1000 mg per the dosage unit.

[0509] Best Mode for Carrying Out the Invention

EXAMPLES

[0510] The present invention is illustrated in more detail by the following Preparations of vasopressin antagonist, vasopressin agonist or oxytocin antagonist, Reference Examples of processes for preparing the starting compounds to be used for preparing the desired compounds of the present invention, and Examples of processes for preparing the desired compounds, and Experiments of the activities of the desired compounds of the present invention.

[0511] Preparation 1

[0512] Film coated tables are prepared from the following components.

1ComponentsAmount7-Chloro-5-[(4-methyl-1-piperazinyl)carbonyl-150 g methyl]-1-[2-methoxy-4-(2-methylphenyl)-benzoyl]-2,3,4,5-tetrahydro-1H-benzazepineAvicel (trademark of microcrystalline cellulose40 gmanufactured by Asahi Chemical Industry,Co., Ltd., Japan)Corn Starch30 gMagnesium stearate 2 gHydroxypropyl methylcellulose10 gPolyethylene glycol-6000 3 gCastor oil40 gEthanol40 g

[0513] The active compound of the present invention, Avicel, corn starch and magnesium stearate are mixed and kneaded and the mixture is tabletted by using a conventional pounder (R 10 mm) for sugar coating. The tablets thus obtained are coated with a film coating agent consisting of hydroxypropyl methylcellulose, polyethylene glycol-6000, castor oil and ethanol to give film coated tablets.

[0514] Preparation 2

[0515] Tablets are prepared from the following components.

2ComponentsAmount7-Chloro-5-{[N-(2-diethylaminoethyl)-N-methyl-150gamino]carbonylmethyl}-1-(3,4-dimethoxybenzoyl)-2,3,4,5-tetrahydro-1H-benzazepineCitric acid1.0gLactose33.5gDicalcium phosphate70.0gPullonic F-6830.0gSodium laurylsulfate15.0gPolyvinylpyrrolidone15.0gPolyethylene glycol (Carbowax 1500)4.5gPolyethylene glycol (Carbowax 6000)45.0gCorn starch30.0gDry sodium stearate3.0gDry magnesium stearate3.0gEthanolq.s.

[0516] The active compound of the present invention, citric acid, lactose, dicalcium phosphate, Pullonic F-68 and sodium laurylsulfate are mixed. The mixture is screened with No. 60 screen and is granulated with an alcohol solution containing polyvinylpyrrolidone, Carbowax 1500 and 6000. If required, an alcohol is added thereto so that the powder mixture is made a paste-like mass. Corn starch is added to the mixture and the mixture is continuously mixed to form uniform particles. The resulting particles are passed through No. 10 screen and entered into a tray and then dried in an oven at 100° C. for 12 to 14 hours. The dried particles are screened with No. 16 screen and thereto are added dry sodium laurylsulfate and dry magnesium stearate, and the mixture is tabletted to form the desired shape.

[0517] The core tablets thus prepared are vanished and dusted with talc in order to guard them from wetting. Undercoating is applied to the core tablets. In order to administer the tablets orally, the core tablets are vanished several times. In order to give round shape and smooth surface to the tablets, further undercoating and coating with a lubricant are applied thereto. The tablets are further coated with a coloring coating materials until the desired colored tablets are obtained. After drying, the coated tablets are polished to obtain the desired tablets having uniform gross.

[0518] Preparation 3

[0519] An injection preparation is prepared from the following components.

3ComponentsAmount7-Chloro-5-[(4-methyl-1-piperazinyl)carbonyl-5gmethyl]-1-[2-methoxy-4-(2,4-dichlorobenzylamino)-benzoyl]-2,3,4,5-tetrahydro-1H-benzazepinePolyethylene glycol (molecular weight; 4000)0.3gSodium chloride0.9gPolyoxyethylene-sorbitan monooleate0.4gSodium metabisulfite0.1gMethyl-paraben0.18gPropyl-paraben0.02gDistilled water for injection10.0ml

[0520] The above parabens, sodium metabisulfite and sodium chloride are dissolved in distilled water of about half volume of the above with stirring at 80° C. The solution thus obtained is cooled to 40° C., and the active compound of the present invention and further polyethylene glycol and polyoxyethylene sorbitan monooleate are dissolved in the above solution. To the solution is added distilled water for injection to adjust to the desired volume, and the solution is sterilized by filtering with an appropriate filter paper to give an injection preparation.

Reference Example 1

[0521] 4-Chloromethylbenzoic acid methyl ester (26.36 g) is dissolved in 1,2-dimethoxyethane (700 ml), and thereto are added with stirring zinc powder (20.6 g) and bistriphenylphosphine palladium dichloride (5 g) over an ice-bath. To the mixture is added dropwise o-toluoyl chloride (26.5 g), and the mixture is stirred over an ice-bath for three hours, and then stirred at room temperature for three days. The insoluble materials are removed by filtration, and the residue is washed with ethyl acetate. To the mother liquor is added a saturated sodium hydrogen carbonate solution, and the mixture is extracted with ethyl acetate. The organic layer is washed successively with a saturated sodium hydrogen carbonate solution, a 0.5N hydrochloric acid and a saturated sodium chloride solution, dried over magnesium sulfate and concentrated. The residue is purified by silica gel column chromatography (solvent; ethyl acetate:n-hexane=50:1˜10:1), and recrystallized from toluene/n-hexane to give 4-[(2-methylbenzoyl)methyl]benzoic acid methyl ester (15 g).

Reference Example 2

[0522] 4-Methoxycarbonylbenzyltriphenylphosphonium chloride (19.1 g) and sodium methylate (2.77 g) are suspended in methanol (20 ml), and the mixture is stirred at room temperature for one hour. To the mixture is added o-chlorobenzaldehyde (5 g), and the mixture is stirred at room temperature for one hour. Sodium methylate (5.54 g) is added to the mixture, and the mixture is stirred at room temperature for one hour. The reaction mixture is concentrated, and to the residue is added water, and the mixture is extracted with ethyl acetate. The organic layer is washed successively with water, a 0.5N hydrochloric acid and a saturated sodium chloride solution, and dried over magnesium sulfate, and concentrated. To the residue is added diethyl ether/n-hexane, and the insoluble materials are removed by filtration. The mother liquor is concentrated, and the residue is purified by silica gel column chromatography (solvent; n-hexane:ethyl acetate=30:1). Methyl 4-(2-chlorostyryl)benzoate (cis form) (2.15 g) is firstly eluted, and then, methyl 4-(2-chlorostyryl)benzoate (trans form) (1.42 g) is eluted, and both are collected as white powder.

Reference Example 3

[0523] A mixture of methyl 4-(2-chlorostyryl)benzoate (trans form) (1.42 g), 5N sodium hydroxide (1.6 ml) and methanol (20 ml) is stirred at room temperature for three hours, and refluxed for two hours. The mixture is evaporated to remove the methanol, and to the residue is added water. The mixture is acidified with conc. hydrochloric acid, and stirred at room temperature for 16 hours. The precipitated crystals are collected by filtration to give 4-(2-chlorostyryl)benzoic acid (1.36 g) as white powder.

Reference Example 4

[0524] 4-Bromobenzoic acid (7.2 g) and thionyl chloride (20 ml) are refluxed for one hour, and concentrated. To the residue is added toluene, and the mixture is concentrated. The obtained 4-bromobenzoic chloride is added dropwise to a mixture of 2-amino-2-methyl-1-propanol (5.1 ml), triethylamine (10 ml) and dichloromethane (70 ml) under ice-cooling. The reaction mixture is stirred at room temperature for five hours, and thereto is added ice, and the mixture is extracted with dichloromethane. The organic layer is washed successively with 0.5N hydrochloric acid, a saturated aqueous sodium hydrogen carbonate solution and a saturated sodium chloride solution, dried over magnesium sulfate, and concentrated. The residue is dissolved in dichloromethane (50 ml), and thereto is added dropwise thionyl chloride (7.8 ml) under ice-cooling. The mixture is stirred at room temperature for three hours, cooled with ice, and basified with a 5N aqueous sodium hydroxide solution. The mixture is extracted with dichloromethane, and the organic layer is washed with water, dried over magnesium sulfate to give 2-(4-bromophenyl)-4,4-dimethyl-2-oxazoline (8.35 g) as colorless oil.

Reference Example 5

[0525] To a solution of 2-(4-bromophenyl)-4,4-dimethyl-2-oxazoline (1 g) in dry tetrahydrofuran (10 ml) are added dropwise magnesium (526 mg) and dry tetrahydrofuran (50 ml) under refluxing. The heating of the mixture is stopped, and thereto is added 2-(4-bromphenyl)-4,4-dimethyl-2-oxazoline (4 g) at a slowly refluxing rate, during which the mixture is stirred for 30 minutes, and then thereto is added o-tolualdehyde (2.16 ml) under ice-cooling. The mixture is stirred under ice-cooling for one hour, and stirred at room temperature for two hours, and the reaction is quenched with adding thereto a saturated aqueous ammonium chloride solution. The mixture is extracted with ethyl acetate, and the organic layer is washed successively with 1N hydrochloric acid, a saturated aqueous sodium hydrogen carbonate solution and a saturated sodium chloride solution, dried over magnesium sulfate, and concentrated. The residue is purified by silica gel column chromatography (solvent; n-hexane:ethyl acetate=4˜2:1) to give 2-{4-[1-(2-methylphenyl)-1-hydroxymethyl]phenyl}-4,4-dimethyl-2-oxazoline (3.07 g) as white powder.

[0526]

1
H-NMR (200 MHz, CDCl3) δ ppm: 1.35 (6H, s), 2.24 (3H, s), 3.04 (1H, d, J=4 Hz), 4.08 (1H, s), 5.99 (1H, d, J=4 Hz), 7.03-7.05 (6H, m), 7.76-7.94 (2H, m)

Reference Example 6

[0527] 2-{4-[1-(2-Methylphenyl)-1-hydroxymethyl]phenyl}-4,4-dimethyl-2-oxazoline (3.0 g), manganese dioxide (20 g) and dichloromethane (50 ml) are mixed at room temperature. The mixture is stirred at room temperature for two hours, and refluxed for three hours. The insoluble materials are removed by filtration through celite, and washed with chloroform, and the mother liquor is concentrated to give 2-[4-(2-methylbenzoyl)phenyl]-4,4-dimethyl-2-oxazoline (2.86 g) as pale yellow oil.

[0528]

1
H-NMR (200 MHz, CDCl3) δ ppm: 1.40 (6H, s), 2.33 (3H, s), 4.14 (2H, s), 7.12-7.54 (4H, m), 7.76-7.92 (2H, m), 7.95-8.14 (2H, m)

Reference Example 7

[0529] 2-[4-(2-Methylbenzoyl)phenyl]-4,4-dimethyl-2-oxazoline (2.86 g) and 4.5M hydrochloric acid (150 ml) are refluxed for 8 hours. The mixture is cooled to room temperature, and thereto is added water. The precipitates are collected by filtration to give 4-(2-methylbenzoyl)benzoic acid (2.23 g) as white powder.

[0530]

1
H-NMR (200 MHz, CDCl3) δ ppm: 2.37 (3H, s), 7.19-7.58 (4H, m), 7.80-8.03 (2H, m), 8.10-8.35 (2H, m), 10.4 (1H, brs)

Reference Example 8

[0531] To a solution of 3-methoxy-4-trifluoromethylsulfonyloxybenzoic acid methyl ester (5 g) in toluene (200 ml) is added tetrakis(triphenylphosphine)palladium (0.9 g) under argon atmosphere, and the mixture is stirred at room temperature for five minutes. To the mixture are added (2-methylphenyl)boric acid (3.2 g), lithium chloride (1.01 g) and a 2M aqueous sodium carbonate solution (11.9 ml), and the mixture is stirred at 100° C. for two hours. To the mixture is added water, and the mixture is filtered through celite to remove the palladium. The filtrate is extracted with diethyl ether, and the ether layer is washed with water, dried, and evaporated. The residue is purified by silica gel column chromatography (solvent; n-hexane→ethyl acetate:n-hexane=1:10) to give 3-methoxy-4-(2-methylphenyl)benzoic acid methyl ester (4.07 g) as oil.

[0532]

1
H-NMR (200 MHz, CDCl3) δ ppm: 2.12 (3H, s), 3.82 (3H, s), 3.95 (3H, s), 7.02-7.48 (5H, m), 7.63 (1H, d, J=1.51 Hz), 7.71 (1H, dd, J=1.5 Hz, 7.74 Hz)

[0533] The suitable starting compounds are treated in the same manner as in Reference Example 8 to give the compounds of Examples 22, 23 and 35-64 as mentioned below.

Reference Example 9

[0534] 2-(4-Phenyl-2-methoxyphenyl)-4,4-dimethyl-2-oxazoline (3.00 g) is dissolved in tetrahydrofuran (30 ml) under argon atmosphere, and the mixture is stirred with cooling over an ice-bath. To the mixture is added dropwise gradually an about 2M solution of 1-n-propylmagnesium bromide in tetrahydrofuran (8.0 ml) at the same temperature. After addition, the mixture is warmed to room temperature, and stirred for 16 hours. The reaction solution is stirred with cooling over an ice-bath, and thereto is added a saturated aqueous ammonium chloride solution (30 ml). The mixture is warmed to room temperature, and the organic layer is collected. The aqueous layer is extracted with ethyl acetate (30 ml×2), and the extract is combined with the organic layer, washed with a saturated aqueous sodium chloride solution (100 ml×2), dried over magnesium sulfate, and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; dichloromethane:n-hexane=1:2→1:1), and evaporated to remove the solvent to give 2-(4-phenyl-2-n-propylphenyl)-4,4-dimethyl-2-oxazoline (2.81 g) as colorless transparent viscous oil.

[0535]

1
H-NMR (200 MHz, CDCl3) δ ppm: 0.98 (3H, t, J=11.3 Hz), 1.39 (6H, s), 1.52-1.77 (2H, m), 2.99 (2H, dd, J=7.5 Hz, J=9.5 Hz), 4.08 (2H, s), 7.30-7.51 (5H, m), 7.52-7.63 (2H, m), 7.78 (1H, d, J=6.5 Hz)

Reference Example 10

[0536] To a mixture of conc. hydrochloric acid (30 ml) and glacial acetic acid (10 ml) is added 2-(4-phenyl-2-n-propylphenyl)-4,4-dimethyl-2-oxazoline (2.70 g), and the mixture is refluxed for three days (nine hours×3). The reaction solution is concentrated to about half volume thereof under reduced pressure, and cooled over an ice-bath. The precipitated crystals are collected by filtration, and purified by silica gel column chromatography (solvent; dichloromethane→dichloromethane:methanol=50:1). The desired fractions are combined, evaporated to remove the solvent, and the crystalline residue is recrystallized from n-hexane to give 4-phenyl-2-n-propylbenzoic acid (1.67 g) as colorless needles.

[0537] M.p. 107.5-108.5° C.

Reference Example 11

[0538] To a solution of 2-(4-bromo-2-methylphenyl)-4,4-dimethyl-2-oxazoline (5 g) in dry tetrahydrofuran (40 ml) is added dropwise a 1.6M solution of n-butyl lithium in n-hexane (14.0 ml) at −70° C. The mixture is stirred at the same temperature for 30 minutes, and thereto is added dropwise cyclohexanone (2.1 ml), and the mixture is stirred for one hour. To the mixture is added water, and the mixture is evaporated to remove the tetrahydrofuran, and then extracted with diethyl ether. The diethyl ether layer is dried over anhydrous magnesium sulfate, evaporated to remove the solvent, and the residue is purified by silica gel column chromatography (solvent; dichloromethane:methanol=100:1˜60:1), recrystallized from acetone/n-hexane to give 2-[4-(1-hydroxy-1-cyclohexyl)-2-methylphenyl]-4,4-dimethyl-2-oxazoline (4.29 g) as white powder.

[0539]

1
H-NMR (200 MHz, CDCl3) δ ppm: 1.14-1.98 (11H, m), 1.38 (6H, s), 2.57 (3H, s), 4.05 (2H, s), 7.19-7.45 (2H, m), 7.72 (1H, d, J=8.1 Hz)

Reference Example 12

[0540] To a solution of 2-[4-(1-hydroxy-1-cyclohexyl)-2-methylphenyl]-4,4-dimethyl-2-oxazoline (4.29 g) in acetic acid (40 ml) is added a 10% dimethyl-2-oxazoline (4.29 g) in acetic acid (40 ml) is added a 10% precipitated crystals are collected by filtration, washed with water, and dried to give 4-cyclohexenyl-2-methylbenzoic acid (2.61 g) as white powder.

[0541]

1
H-NMR (200 MHz, CDCl3) δ ppm: 1.55-1.93 (4H, m), 2.13-2.31 and 2.32-2.56 (each 2H, each m), 2.66 (3H, s), 6.17-6.34 (1H, m), 7.15-7.42 (2H, m), 7.90-8.18 (1H, m)

Reference Example 13

[0542] To a solution of 4-cyclohexenyl-2-methylbenzoic acid (2.61 g) in ethanol (30 ml) and ethyl acetate (30 ml) is added 5% palladium-carbon (0.4 g), and the mixture is stirred at room temperature under atmospheric pressure of hydrogen gas for 30 minutes. The palladium-carbon is removed by filtration through celite, and the filtrate is evaporated to remove the solvent. The precipitated crystals are collected by filtration, crystallized from acetone/n-hexane, and washed to give 4-cyclohexyl-2-methylbenzoic acid (2.27 g) as white powder.

[0543] M.p. 129-130° C.

Reference Example 14

[0544] 4-Phenylpiperidine (0.5 g), p-fluorobenzonitrile (0.37 g) and potassium carbonate (0.78 g) are dissolved in N-methylpiperidone (5 ml), and the mixture is stirred at 120° C. for five hours. To the reaction solution is added ethyl acetate (50 ml), and the mixture is washed with water, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. To the resulting residue is added methanol, and the insoluble crystals are collected by filtration, dried under reduced pressure to give 4-phenyl-1-(4-cyanophenyl)piperidine (0.39 g) as white needles.

[0545] M.p. 167-169° C.

Reference Example 15

[0546] To 4-phenyl-1-(4-cyanophenyl)piperidine (0.39 g) are added acetic acid (10 ml) and conc. hydrochloric acid (10 ml), and the mixture is refluxed for five hours. The reaction solution is concentrated, and to the residue is added diethyl ether/methanol. The insoluble crystals are collected by filtration, and dried under reduced pressure to give 4-phenyl-1-(4-carboxyphenyl)piperidine (0.39 g) as white powder.

[0547] M.p. 257-259° C. (decomposed)

Reference Example 16

[0548] Homopiperazine (100 g) is dissolved in ethanol (500 ml), and thereto is added dropwise gradually ethyl iodide (19.8 ml). The mixture is stirred at room temperature overnight, and the insoluble materials are removed by filtration. The filtrate is evaporated to remove the solvent. Purification is performed by distillation to give 1-ethylhomopiperazine (50 g) as colorless oil.

[0549] B.p. 86-88° C./37 mmHg

[0550]

1
H-NMR (200 MHz, CDCl3) δ ppm: 1.06 (3H, t, J=7.2 Hz), 1.68-1.93 (2H, m), 2.54 (2H, q, J=7.2 Hz), 2.63-2.76 (7H, m), 2.87-3.01 (2H, m)

Reference Example 17

[0551] To a solution of 4-phenyl-2-chloro-1-trifluoromethylsulfonyloxybenzene (35 g) in dimethylformamide (300 ml) are added palladium acetate (1.17 g), 1,3-bis(diphenylphosphino)propane (4.29 g), ethanol (91.5 ml) and triethylamine (29.0 ml) under carbon monooxide atmosphere, and the mixture is heated with stirring at 80-90° C. for 6 hours. To the reaction solution is added water, and further added a small amount of n-hexane. The mixture is extracted with ethyl acetate, and the ethyl acetate layer is washed with water, dried, and the residue is purified by silica gel column chromatography (solvent; n-hexane→ethyl acetate:n-hexane=1:100) to give ethyl 4-phenyl-2-chlorobenzoate (20.9 g) as colorless oil.

[0552]

1
H-NMR (200 MHz, CDCl3) δ ppm: 1.42 (3H, t, J=7.0 Hz), 4.42 (2H, q, J=7.0 Hz), 7.28-7.78 and 7.85-8.18 (all 8H, m)

[0553] The suitable starting compounds are treated in the same manner as in Reference Example 17 to give the following compounds.

Reference Example 18Structure:

p: 1 R8: 2-ClR23: —COOCH3Crystalline form: Brown OilForm: FreeReference Example 19Structure:

p: 1 R8: 2-ClR23: —COOCH3Crystalline form: Brown OilForm: FreeReference Example 20Structure:

p: 1 R8: 2-ClR23: —COOCH3Crystalline form: White powderForm: FreeReference Example 21Structure:

p: 1 R8: 2-ClR23: —COOCH3Crystalline form: Yellow oilForm: FreeReference Example 22Structure:

p: 1 R8: 2-CH3R23: —COOCH3Crystalline form: White powderForm: FreeReference Example 23Structure:

100

p: 1 R8: 2-NO2R23: —COOCH3Crystalline form: Yellow viscous oilForm: FreeReference Example 24Structure:

101

p: 1 R8: 2-ClR23: —COOCH3Crystalline form: White powderForm: FreeReference Example 25Structure:

102

p: 1 R8: 2-CH3R23: —COOCH3Crystalline form: Pale yellow solidForm: FreeReference Example 26Structure:

103

p: 1 R8: 2-CH3R23: —COOCH3Crystalline form: Pale yellow powderForm: FreeReference Example 27Structure:

104

p: 1 R8: HR23: —COOCH3Crystalline form: Pale yellow powderSolvent for recrystallization: Chloroform/diethyl etherM.p. 96-98° C.Form: FreeReference Example 28Structure:

105

p: 1 R8: HR23: —COOCH3Crystalline form: Pale yellow powderSolvent for recrystallization: Chloroform/diethyl etherM.p. 100-102° C.Form: FreeReference Example 29Structure:

106

p: 1 R8: HR23: —COOCH3Crystalline form: Pale brown powderSolvent for recrystallization: Chloroform/diethyl etherM.p. 126-128° C.Form: FreeReference Example 30Structure:

107

p: 1 R8: HR23: —COOCH3Crystalline form: Brown oilForm: FreeReference Example 31Structure:

108

p: 1 R8: HR23: —COOCH3Crystalline form: Pale brown oilForm: FreeReference Example 32Structure:

109

p: 1 R8: HR23: —COOCH3Crystalline form: Pale yellow oilForm: FreeReference Example 33Structure:

110

p: 1 R8:R23: —COOCH3Crystalline form: Pale yellow oilForm: FreeReference Example 34Structure:

111

p: 1 R8: 2-CH3R23: —COOCH3Crystalline form: Brown oilForm: FreeReference Example 35Structure:

112

p: 1 R8: HR23: —COOCH3Crystalline form: Colorless oilForm: FreeReference Example 36Structure:

113

p: 1 R8: 2-OCH3R23: —COOCH3Crystalline form: Slightly yellow oilForm: FreeReference Example 37Structure:

114

p: 1 R8: 2-OCH3R23: —COOCH3Crystalline form: Colorless oilForm: FreeReference Example 38Structure:

115

p: 1 R8: 2-OCH3R23: —COOCH3Crystalline form: Colorless oilForm: FreeReference Example 39Structure:

116

p: 2 R8: 3,5-di-OCH3R23: —COOCH3Crystalline form: Colorless prismsForm: FreeReference Example 40Structure:

117

p: 1 R8: 3-OCH3R23: —COOCH3Crystalline form: Colorless oilForm: FreeReference Example 41Structure:

118

p: 1 R8: HR23: —COOCH3Crystalline form: White powderForm: FreeReference Example 42Structure:

119

p: 1 R8: 2-OCH3R23: —COOCH3Crystalline form: Colorless oilForm: FreeReference Example 43Structure:

120

p: 1 R8: HR23: —CO2C2H5Crystalline form: White powderForm: FreeReference Example 44Structure:

121

p: 1 R8: HR23: —CO2C2H5Crystalline form: Colorless oilForm: FreeReference Example 45Structure:

122

p: 1 R8: HR23: —CO2C2H5Crystalline form: White powderForm: FreeReference Example 46Structure:

123

p: 1 R8: 2-CH3R23: —CO2CH3Crystalline form: Slightly yellow oilForm: FreeReference Example 47Structure:

124

p: 1 R8: 2-OCH3R23: —CO2CH3Crystalline form: White powderForm: FreeReference Example 48Structure:

125

p: 1 R8: 2-OCH3R23: —CO2CH3Crystalline form: Colorless oilForm: FreeReference Example 49Structure:

126

p: 1 R8: 2-CH3R23: —CO2CH3Crystalline form: White powderForm: FreeReference Example 50Structure:

127

p: 1 R8: 2-CH3R23: —CO2CH3Crystalline form: White powderForm: FreeReference Example 51Structure:

128

p: 1 R8: 3-OCH3R23: —CO2CH3Crystalline form: Colorless oilForm: FreeReference Example 52Structure:

129

p: 2 R8: 3,5-di-OCH3R23: —CO2CH3Crystalline form: White powderForm: FreeReference Example 53Structure:

130

p: 1 R8: 2-OCH3R23: —CO2CH3Crystalline form: Colorless prismsForm: FreeReference Example 54Structure:

131

p: 1 R8: 2-CH3R23: —CO2CH3Crystalline form: Colorless oilForm: FreeReference Example 55Structure:

132

p: 1 R8: HR23: —CO2CH3Crystalline form: White powderForm: FreeReference Example 56Structure:

133

p: 1 R8: HR23: —CO2CH3Crystalline form: White powderForm: FreeReference Example 57Structure:

134

p: 1 R8: 2-CH3R23: —CO2CH3Crystalline form: Colorless prismsForm: FreeReference Example 58Structure:

135

p: 1 R8: 2-OCH3R23: —CO2CH3Crystalline form: Colorless oilForm: FreeReference Example 59Structure:

136

p: 1 R8: 2-CH3R23: —CO2CH3Crystalline form: White powderForm: FreeReference Example 60Structure:

137

p: 1 R8: 2-CH3R23: —CO2CH3Crystalline form: Slightly yellow powderForm: FreeReference Example 61Structure:

138

p: 1 R8: 2-ClR23: —CO2C2H5Crystalline form: Colorless oilForm: FreeReference Example 62Structure:

139

p: 1 R8: 2-CH3R23: —CO2CH3Crystalline form: Slightly yellow powderForm: FreeReference Example 63Structure:

140

p: 1 R8: 2-CH3R23: —CO2CH3Crystalline form: White powderForm: FreeReference Example 64Structure:

141

p: 1 R8: 2-CH3R23: —CO2CH3Crystalline form: White powderForm: Free

[0554] The suitable starting compounds are treated in the same manner as in Reference Example 3, 7, 10 or 12 to give the following compounds.

142

Reference Example 65Structure:

143

p: 1 R8: 2-ClCrystalline form: White powderForm: FreeReference Example 66Structure:

144

p: 1 R8: 2-ClCrystalline form: Yellow powderForm: FreeReference Example 67Structure:

145

p: 1 R8: 2-ClCrystalline form: White powderForm: FreeReference Example 68Structure:

146

p: 1 R8: 2-ClCrystalline form: White powderForm: FreeReference Example 69Structure:

147

p: 1 R8: HCrystalline form: White powderM.p. 257-259° C. (decomposed)Form: FreeReference Example 70Structure:

148

p: 1 R8: 2-CH3Crystalline form: White powderForm: FreeReference Example 71Structure:

149

p: 1 R8: HCrystalline form: Brown powderM.p. 233-235° C.,Form: FreeReference Example 72Structure:

150

p: 1 R8: 2-C2H5Crystalline form: Colorless platesSolvent for recrystallization: n-Hexane/chloroformM.p. 164-165° C.Form: FreeReference Example 73Structure:

151

p: 1 R8: 2-n-C3H7Crystalline form: Colorless needlesSolvent for recrystallization: n-HexaneM.p. 107.5-108.5° C.Form: FreeReference Example 74Structure:

152

p: 1 R8: 2-NO2Crystalline form: Red brown powderM.p. 199-201° C.Form: FreeReference Example 75Structure:

153

p: 1 R8: 2-ClCrystalline form: White powderForm: FreeReference Example 76Structure:

154

p: 1 R8: 2-ClCrystalline form: White powderForm: FreeReference Example 77Structure:

155

p: 1 R8: 2-ClCrystalline form: Slightly red powderForm: FreeReference Example 78Structure:

156

p: 1 R8: HCrystalline form: White powderForm: FreeReference Example 79Structure:

157

p: 1 R8: HCrystalline form: White powderForm: FreeReference Example 80Structure:

158

p: 1 R8: 2-CH3Crystalline form: White powderForm: HydrochlorideReference Example 81Structure:

159

p: 1 R8: HCrystalline form: Brown powderForm: FreeReference Example 82Structure:

160

p: 1 R8: 2-OCH3Crystalline form: Pale brown powderSolvent for recrystallization: Chloroform/diethyl etherM.p. 133-135° C.Form: FreeReference Example 83Structure:

161

p: 1 R8: 3-OCH3Crystalline form: Brown powderSolvent for recrystallization: Chloroform/diethyl etherM.p. 126-128° C.Form: FreeReference Example 84Structure:

162

p: 1 R8: HCrystalline form: White powderSolvent for recrystallization: Chloroform/diethyl etherM.p. 198-201° C.Form: FreeReference Example 85Structure:

163

p: 1 R8: HCrystalline form: White powderSolvent for recrystillization: Chloroform/diethyl etherM.p. 236-239° C.Form: FreeReference Example 86Structure:

164

p: 1 R8: HCrystalline form: White needlesSolvent for recrystallization: Methanol/diethyl etherM.p. 257-260° C.Form: FreeReference Example 87Structure:

165

p: 1 R8: HCrystalline form: Pale brown powderSolvent for recrystallization: Methanol/diethyl etherM.p. 201-203° C.Form: FreeReference Example 88Structure:

166

p: 1 R8: HCrystalline form: White powderSolvent for recrystallization: Methanol/diethyl etherM.p. 230° C. (decomposed)Form: HydrochlorideReference Example 89Structure:

167

p: 1 R8: HCrystalline form: White powderSolvent for recrystallization: Methanol/diethyl etherM.p. 206-207° C.Form: HydrochlorideReference Example 90Structure:

168

p: 1 R8: HCrystalline form: Pale yellow powderSolvent for recrystallization: Ethanol/diethyl etherM.p. 266-269° C.Form: HydrochlorideReference Example 91Structure:

169

p: 1 R8: 2-CH3Crystalline form: Pale yellow powderSolvent for recrystallization: MethanolM.p. 276-279° C.Form: HydrochlorideReference Example 92Structure:

170

p: 1 R8: HCrystalline form: White powderSolvent for recrystallization: Methanol/diethyl etherM.p. 161-163° C.Form: FreeReference Example 93Structure:

171

Crystalline form: Pale yellow powderSolvent for recrystallization: Methanol/diethyl etherMp.p 250-251° C.Form: FreeReference Example 94Structure:

172

p: 1 R8: HCrystalline form: Yellow amorphousForm: FreeReference Example 95Structure:

173

p: 1 R8: HCrystaqlline form: White needlesForm: FreeReference Example 96Structure:

174

p: 1 R8: HCrystalline form: Pale yellow needlesSolvent for recrystallization: Methanol/diethyl etherM.p. 309-311° C.Form: HydrochlorideReference Example 97Structure:

175

p: 1 R8: 2-CH3Crystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 198-200° C.Form: FreeReference Example 98Structure:

176

p: 1 R8: 2-CH3Crystalline form: White powderForm: FreeReference Example 99Structure:

177

p: 1 R8: 2-CH3Crystalline form: White powderForm: FreeReference Example 100Structure:

178

p: 1 R8: 2-CH3Crystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 208° C.Form: FreeReference Example 101Structure:

179

p: 1 R8: 2-CH3Crystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneMp.p 234-236° C.Form: FreeReference Example 102Structure:

180

p: 1 R8: 2-CH3Crystalline form: White powderForm: FreeReference Example 103Structure:

181

p: 1 R8: 2-OCH3Crystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 132-133° C.Form: FreeReference Example 104Structure:

182

p: 1 R8: 2-OCH3Crystalline form: Colorless prismsSolvent for recrystallization: Ethyl acetateM.p. 153-154° C.Form: FreeReference Example 105Structure:

183

p: 1 R8: 2-OCH3Crystalline form: Colorless prismsSolvent for recrystallization: Ethyl acetateM.p. 118-119° C.Form: FreeReference Example 106Structure:

184

p: 2 R8: 3,5-di-OCH3Crystalline form: White powderSolvent for recrystillization: Acetone/n-hexaneM.p. 239-240° C.Form: FreeReference Example 107Structure:

185

p: 1 R8: 3-OCH3Crystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 179-182° C.Form: FreeReference Example 108Structure:

186

p: 1 R8: HCrystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 194-197° C.Form: FreeReference Example 109Structure:

187

p: 1 R8: 2-OCH3Crystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 149-150° C.Form: FreeReference Example 110Structure:

188

p: 1 R8: HCrystalline form: White powderSolvent for recrystallization: Ethanol/diethyl etherM.p. 202-204° C.Form: FreeReference Example 111Structure:

189

p: 1 R8: HCrystalline form: White powderForm: FreeReference Example 112Structure:

190

p: 1 R8: 2-OCH3Crystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 134-135° C.Form: FreeReference Example 113Structure:

191

p: 1 R8: 2-OCH3Crystalline form: White powderForm: FreeReference Example 114Structure:

192

p: 1 R8: 2-CH3Crystalline form: White powderForm: FreeReference Example 115Structure:

193

p: 1 R8: 2-CH3Crystalline form: White powderSolvent for recrystallization: Ethanol/diethyl etherM.p. 262-265° C.Form: FreeReference Example 116Structure:

194

p: 1 R8: 3-OCH3Crystalline form: White powderForm: FreeReference Example 117Structure:

195

p: 1 R8: 3-OCH3Crystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 146-147° C.Form: FreeReference Example 118Structure:

196

p: 1 R8: 2-CH3Crystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 132-133° C.Form: FreeReference Example 119Structure:

197

p: 1 R8: 2-CH3Crystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 129-130° C.Form: FreeReference Example 120Structure:

198

p: 1 R8: 2-CH3Crystalline form: White powderForm: FreeReference Example 121Structure:

199

p: 1 R8: 2-CH3Crystalline form: Pale yellow powderForm: FreeReference Example 122Structure:

200

p: 1 R8: HCrystalline form: White powderForm: FreeReference Example 123Structure:

201

p: 1 R8: HCrystalline form: White powderForm: FreeReference Example 124Structure:

202

p: 2 R8: 3,5-di-OCH3Crystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 231-232° C.Form: FreeReference Example 125Structure:

203

p: 1 R8: 2-OCH3Crystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 159-160° C.Form: FreeReference Example 126Structure:

204

p: 1 R8: 2-CH3Crystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 117-118° C.Form: FreeReference Example 127Structure:

205

p: 1 R8: HCrystalline form: White powderSolvent for recrystaillization: Ethanol/diethyl etherM.p. 246-248° C.Form: FreeReference Example 128Structure:

206

p: 1 R8: HCrystalline form: Colorless prismsSolvent for recrystallization: Acetone/n-hexaneM.p. 185-187° C.Form: FreeReference Example 129Structure:

207

p: 1 R8: 2-CH3Crystalline form: White powderForm: FreeReference Example 130Structure:

208

p: 1 R8: 2-OCH3Crystalline form: White powderSolvent for recrystaillization: Acetone/n-hexaneM.p. 145-148° C.Form: FreeReference Example 131Structure:

209

p: 1 R8: 2-ClCrystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 164° C.Form: Free

[0555] The suitable starting compounds are treated in the same manner as in Reference Example 17 to give the following compounds.

6Reference Example 132Structure:

210

Crystalline form: White needles1H-NMR (200 MHz, CDCl3) δ ppm: 3.97 (3H, s), 7.48-7.62 (3H, m),7.81 (1H, dd, J = 8.0 Hz, J = 0.8 Hz), 7.98-8.17 (2H, m), 8.34 (1H,dd, J = 8.0 Hz, J = 2.2 Hz), 9.28 (1H, dd, J = 2.2 Hz, J = 0.8 Hz)Form: FreeReference Example 133Structure:

211

Crystalline form: White powder1H-NMR (200 MHz, CDCl3) δ ppm: 2.38 (3H, s), 3.98 (3H, s), 7.19-7.50(4H, m), 7.50 (1H, dd, J = 8.0 Hz, J = 0.8 Hz), 8.35 (1H, dd, J = 8.0 Hz,J = 2.0 Hz), 9.30 (1H, dd, J = 2.0 Hz, J = 0.8 Hz)Form: FreeReference Example 134Structure:

212

Crystalline form: Pale brown powderSolvent for recrystallization: Chloroform/diethyl etherM.p. 110-111° C.Form: Free

[0556] The suitable starting compounds are treated in the same manner as in Reference Example 3, 7, 10 or 12 to give the following compounds.

7Reference Example 135Structure:

213

Crystalline form: Colorless needlesM.p. 191-192° C.Form: FreeReference Example 136Structure:

214

Crystalline form: Colorless needlesM.p. 228-230° C.Form: FreeReference Example 137Structure:

215

Crystalline form: Pale brown needlesSolvent for recrystallization: Methanol/diethyl etherM.p. 253-255° C.Form: Hydrochloride

[0557] The suitable starting compounds are treated in the same manner as in Reference Example 17 to give the following compounds.

216

Reference Example 138Structure:

217

p: 1R8: HR23: —CO2C2H5Crystalline form: White powder1H-NMR (200 MHz, DMSO-d6) δ ppm: 6.80-6.95 (1H, m),7.20-7.35 (1H, m), 7.55-7.65 (1H, m), 7.98-8.16 (4H, m), 8.45-8.60(2H, m), 1.34 (3H, t, J = 7.2 Hz), 4.33 (2H, q, J = 7.2 Hz)Reference Example 139Structure:

218

p: 1R8: HR23: —CO2C2H5Crystalline form: White powder1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.34 (3H, t,J = 7.2 Hz), 2.29 (3H, s), 4.33 (2H, q, J = 7.2 Hz),7.10-7.20 (1H, m), 7.50-7.58 (1H, m), 7.95-8.15 (4H, m),8.33 (1H, s), 8.43 (1H, s)Reference Example 140Structure:

219

p: 1R8: HR23: —CO2C2H5Crystalline form: White powder1H-NMR (200 MHz, CDCl3) δ ppm: 1.40 (3H, t,J = 7.2 Hz), 4.21 (2H, s), 4.37 (2H, q, J = 7.2 Hz), 7.60-7.70 (2H, m), 8.00-8.11 (2H, m), 8.42 (1H, brs)Reference Example 141Structure:

220

p: 1R8: 2-CH3R23: —CO2CH3Crystalline form: White powder1H-NMR (200 MHz, CDCl3) δ ppm: 2.61 (3H, s), 3.88 (3H, s),4.20 (2H, s), 7.40-7.55 (2H, m), 7.90-8.01 (1H, m), 8.30 (1H, brs)

[0558] The suitable starting compounds are treated in the same manner as in Reference Example 3, 7, 10 or 12 to give the following compounds.

221

Reference Example 142Structure:

222

p: 1R8: HCrystalline form: White powder1H-NMR (200 MHz, DMSO-d6) δ ppm: 7.40-7.55 (1H, m),7.85-8.03 (2H, m), 8.03-8.25 (4H, m), 8.85-9.00 (2H, m),12.4-14.1 (1H, brs)Reference Example 143Structure:

223

p: 1R8: HCrystalline form: White powder1H-NMR (200 MHz, DMSO-d6) δ ppm: 2.41 (3H, s), 7.75-7.95 (2H, m),7.95-8.25 (4H, m), 8.70 (1H, s), 8.85 (1H, s), 12.6-13.6 (1H, brs)Reference Example 144Structure:

224

p: 1R8: HCrystalline form: Light brown powder1H-NMR (200 MHz, CDCl3) δ ppm: 2.07 (6H, s), 5.94 (2H, s), 7.30-7.40(2H, m), 8.20-8.30 (2H, m), 10.7-12.1 (1H, brs)

[0559] The data of NMR analysis of the compounds of the above Reference Examples are as follows.

[0560] The suitable starting compounds are treated in the same manner as in Reference Example 17 to give the following compounds.

225

Reference Example 145Structure:

226

p: 1R8: 2-CH3R23: —COOCH3Crystalline form: Pale yellow oilForm: FreeReference Example 146Structure:

227

p: 1R8: 2-ClR23: —COOCH3Crystalline form: Yellow prismsForm: FreeReference Example 147Structure:

228

p: 1R8: 2-ClR23: —COOCH3Crystalline form: Yellow needlesForm: FreeReference Example 148Structure:

229

p: 1R8: 2-CH3R23: —COOCH3Crystalline form: Colorless viscous oilForm: FreeReference Example 149Structure:R9: 4-OHp: 1R8: 2-CH3R23: —COOCH3Crystalline form: White powderSolvent for recrystallization: n-Hexane/ethyl acetateM.p. 97-98.5° C.Form: FreeReference Example 150Structure:R9: 4-OCH(CH3)2p: 1R8: 2-CH3R23: —COOCH3Crystalline form: Colorless viscous oilForm: FreeReference Example 151Structure:R9: 4-O(CH2)3CH3p: 1R8: 2-CH3R23: —COOCH3Crystalline form: Colorless viscous oilForm: FreeReference Example 152Structure:R9: 4-OCH2CH(CH3)2p: 1R8: 2-CH3R23: —COOCH3Crystalline form: Colorless viscous oilForm: FreeReference Example 153Structure:R9: 4-NHCOCF3p: 1R8: 2-ClR23: —COOCH3Crystalline form: White powderForm: FreeReference Example 154Structure:R9: 4-OCH2COOHp: 1R8: 2-CH3R23: —COOCH3Crystalline form: White powderSolvent for recrystallization: Dichloromethane/n-hexaneForm: FreeReference Example 156Structure:

230

p: 1R8: 2-ClR23: —COOCH3Solvent for recrystallization: Ethyl acetate/n-hexaneM.p. 118-123° C.Form: FreeReference Example 157Structure:

231

p: 1R8: 3-OCH3R23: —COOCH3Crystalline form: White powderForm: FreeReference Example 158Structure:

232

p: 1R8: 3-OCH3R23: —COOCH3Crystalline form: White powderForm: FreeReference Example 159Structure:

233

p: 1R8: 3-OCH3R23: —COOCH3Crystalline form: Colorless oilForm: FreeReference Example 160Structure:

234

p: 1R8: 3-OCH3R23: —COOCH3Reference Example 161Structure:R9: 4-NHCOO(CH2)2C(CH3)3p: 1R8: 2-OCH3R23: —COOCH3Crystalline form: Colorless oilForm: FreeThe suitable starting compounds are treated in the same manneras in Reference Example 3, 7, 10 or 12 to give the following compounds.

235

Reference Example 162Structure:

236

p: 1R8: 2-CH3Crystalline form: Pale brown powderSolvent for recrystallization: Chloroform/diethyl etherForm: FreeReference Example 163Structure:

237

p: 1R8: 2-CH3Crystalline form: White powderSolvent for recrystallization: Ethanol/diethyl etherForm: HydrochlorideReference Example 164Structure:

238

p: 1R8: 2-ClCrystalline form: White powderForm: HydrochlorideReference Example 165Structure:

239

p: 1R8: 2-ClCrystalline form: White powderForm: FreeReference Example 166Structure:

240

p: 1R8: 2-CH3Crystalline form: White powderSolvent for recrystallization: Ethyl acetate/n-hexaneM.p. 127.5-130° C.Form: FreeReference Example 167Structure:R9: 4-OCH(CH3)2p: 1R8: 2-CH3Crystalline form: White powderForm: FreeReference Example 168Structure:R9: 4-O(CH2)3CH3p: 1R8: 2-CH3Crystalline form: White powderForm: FreeReference Example 169Structure:R9: 4-OCH2CH(CH3)2p: 1R8: 2-CH3Crystalline form: Pale yellow powderForm: FreeReference Example 170Structure:

241

p: 1R8: 2-ClCrystalline form: White powderForm: FreeReference Example 171Structure:

242

p: 1R8: 2-CH3Crystalline form: White powderForm: FreeReference Example 172Structure:

243

p: 1R8: 2-ClCrystalline form: White powderForm: FreeReference Example 174Structure:R9: 4-CH2CH(CH3)2p: 1R8: 2-CH3Crystalline form: White powderForm: FreeReference Example 175Structure:

244

p: 1R8: 2-CH3Crystalline form: Yellow powderForm: FreeReference Example 176Structure:

245

p: 1R8: 3-OCH3Crystalline form: White powderForm: FreeReference Example 177Structure:

246

p: 1R8: 3-OCH3Crystalline form: White powderM.p. 170-171° C.Form: FreeReference Example 178Structure:

247

p: 1R8: 3-OCH3Crystalline form: White powderM.p. 128-129° C.Form: FreeReference Example 179Structure:

248

p: 1R8: 3-OCH3Crystalline form: White powderM.p. 146-147° C.Form: FreeReference Example 180Structure:R9: 4-NHCOO(CH2)2C(CH3)3p: 1R8: 2-OCH3Crystalline form: White powderForm: Free

[0561] The data of NMR analysis of the compounds of the above Reference Examples are as follows.

[0562] NMR analysis:

[0563] The compound of Reference Example 18 1H-NMR (200 MHz, CDCl3) δ ppm: 1.90-3.06 [all 9H, m, 2.38 (s)], 3.30-3.72 (4H, m), 3.85 (3H, s), 6.34-6.81 [all 2H, m, 6.53 (dd, J=8.93 Hz, J=8.99 Hz), 6.67 (d, J=2.32 Hz)], 7.83 (1H, d, J=8.95 Hz)

[0564] The compound of Reference Example 19 1H-NMR (200 MHz, CDCl3) δ ppm: 2.92-3.60 (all 8H, m), 3.88 (3H, s), 6.79-7.48 and 7.78-7.79 [all 8H, m, 6.79 (dd, J=8.92 Hz, J=8.92 Hz)]

[0565] The compound of Reference Example 20 1H-NMR (200 MHz, CDCl3) δ ppm: 1.68-2.09 [all 4H, m, 1.77 (d, J=3.30 H), 1.84 (d, J=4.20 Hz)], 2.61-3.12 (all 3H, m), 3.75-4.10 [all 5H, m, 3.87 (s)], 6.78 (1H, dd, J=8.96 Hz, J=8.97 Hz), 6.92 (1H, d, J=2.58 Hz), 7.15-7.41 (all 5H, m), 7.86 (1H, d, J=8.92 Hz)

[0566] The compound of Reference Example 21 1H-NMR (200 MHz, CDCl3) δ ppm: 2.57 (3H, t, J=5.21 Hz), 3.31 (3H, t, J=5.23 Hz), 3.55 (2H, s), 3.86 (3H, s), 6.72 (1H, dd, J=8.95 Hz, J=8.94 Hz), 6.85 (1H, d, J=2.56 Hz), 7.19-7.49 (5H, m), 7.82 (1H, d, J=8.91 Hz)

[0567] The compound of Reference Example 22 1H-NMR (200 MHz, CDCl3) δ ppm: 2.66 (3H, s), 3.85 (3H, s), 3.89 (3H, s), 6.81-7.60 (6H, m), 7.85-8.08 (1H, m)

[0568] The compound of Reference Example 23 1H-NMR (200 MHz, CDCl3) δ ppm: 3.94 (3H, s), 7.39-7.70 (5H, m), 7.79-7.92 (2H, m), 8.02-8.11 (1H, m)

[0569] The compound of Reference Example 24 1H-NMR (200 MHz, DMSO-d6) δ ppm: 3.4-3.55 (2H, m), 3.8 (3H, s), 3.8-3.95 (2H, m), 7.36 (1H, s), 7.50 (1H, dd, J=8.8 Hz, J=2 Hz), 7.82 (1H, d, J=8.8 Hz), 7.86 (1H, d, J=2 Hz)

[0570] The compound of Reference Example 25 1H-NMR (200 MHz, CDCl3) δ ppm: 2.67 (3H, s), 3.93 (3H, s), 7.22-7.43 (3H, m), 7.95-8.08 (1H, m), 8.48-8.63 (1H, m), 8.65-8.75 (1H, m)

[0571] The compound of Reference Example 26 1H-NMR (200 MHz, CDCl3) δ ppm: 2.69 (3H, s), 3.93 (3H, s), 7.41-7.63 (4H, m), 7.95-8.08 (1H, m), 8.62-8.76 (2H, m)

[0572] The compound of Reference Example 30 1H-NMR (200 MHz, CDCl3) δ ppm: 0.88 (3H, t, J=7.4 Hz), 1.05 (3H, t, J=7.4 Hz), 1.80 (3H, hept, J=7.4 Hz), 4.00 (2H, t, J=7.4 Hz), 4.31 (3H, t, J=7.4 Hz), 7.06 (1H, d, J=1.1 Hz), 7.17 (1H, d, J=1.1 Hz), 7.60-7.76 (2H, m), 8.06-8.22 (2H, m)

[0573] The compound of Reference Example 31 1H-NMR (200 MHz, CDCl3) δ ppm: 3.68 (3H, s), 7.20-7.36 (1H, m), 7.40-7.66 (4H, m), 7.66-7.90 (2H, m), 8.58-8.74 (1H, m)

[0574] The compound of Reference Example 32 1H-NMR (200 MHz, CDCl3) δ ppm: 3.96 (3H, s), 7.22-7.35 (1H, m), 7.56 (1H, t, J=7.8 Hz), 7.72-7.86 (2H, m), 8.09 (1H, dt, J=1.5 Hz, J=7.8 Hz), 8.24 (1H, ddd, J=1.2 Hz, J=1.8 Hz, J=7.8 Hz), 8.65 (1H, t, J=1.6 Hz), 8.69-8.77 (1H, m)

[0575] The compound of Reference Example 33 1H-NMR (250 MHz, CDCl3) δ ppm: 3.96 (3H, s), 7.39 (1H, ddd, J=0.8 Hz, J=4.8 Hz, J=7.8 Hz), 7.57 (1H, t, J=7.8 Hz), 7.75-7.83 (1H, m), 7.87-7.97 (1h, m), 8.08 (1H, dt, J=1.3 Hz, J=7.8 Hz), 8.27 (1H, t, J=1.6 Hz), 8.63 (1H, dd, J=1.6 Hz, J=4.8 Hz), 8.88 (1H, dd, J=0.7 Hz, J=2.4 Hz)

[0576] The compound of Reference Example 34 1H-NMR (250 MHz, CDCl3) δ ppm: 2.69 (3H, s), 3.92 (3H, s), 7.32-7.53 (3H, m), 7.89 (1H, ddd, J=1.7 Hz, J=2.3 Hz, J=7.1 Hz), 8.03 (1H, d, J=8.6 Hz), 8.63 (1H, dd, J=1.6 Hz, J=4.8 Hz), 8.86 (1H, dd, J=0.7 Hz, J=1.6 Hz)

[0577] The compound of Reference Example 35 1H-NMR (250 MHz, CDCl3) δ ppm: 3.95 (3H, s), 7.32-7.56 (4H, m), 7.59-7.66 (2H, m), 7.75-7.83 (1H, m), 7.99-8.07 (1H, m), 8.25-8.33 (1H, m)

[0578] The compound of Reference Example 36 1H-NMR (200 MHz, CDCl3) Δ ppm: 2.27 (3H, s), 3.91 (3H, s), 3.92 (3H, s), 6.86-7.04 (2H, m), 7.16-7.41 (4H, m), 7.76-7.96 (1H, m)

[0579] The compound of Reference Example 37 1H-NMR (200 MHz, CDCl3) δ ppm: 3.81, 3.90 and 3.93 (each 3H, each s), 6.87-7.23 (4H, m), 7.29-7.52 (2H, m), 7.76-7.92 (1H, m)

[0580] The compound of Reference Example 38 1H-NMR (200 MHz, CDCl3) δ ppm: 3.91 and 3.97 (each 3H, each s), 7.11-7.28 (2H, m), 7.32-7.55 (3H, m), 7.56-7.70 (2H, m), 7.89 (1H, d, J=8.0 Hz

[0581] The compound of Reference Example 39 1H-NMR (200 MHz, CDCl3) δ ppm: 2.39 (3H, s), 3.79 (6H, s), 3.95 (3H, s), 7.23 (4H, s), 7.33 (2H, s)

[0582] The compound of Reference Example 40 1H-NMR (200 MHz, CDCl3) δ ppm: 3.87 and 3.94 (each 3H, each s), 7.21-7.50 (4H, m), 7.51-7.61 (2H, m), 7.62-7.83 (2H, m)

[0583] The compound of Reference Example 41 1H-NMR (200 MHz, CDCl3) δ ppm: 2.43 and 3.94 (each 3H, each s), 7.08-7.29 (1H, m), 7.30-7.50 (3H, m), 7.58-7.72 (2H, m), 8.02-8.18 (2H, m)

[0584] The compound of Reference Example 42 1H-NMR (200 MHz, CDCl3) δ ppm: 2.24, 2.37, 3.90 and 3.91 (each 3H, each s), 6.78-6.98 (2H, m), 7.00-7.19 (3H, m), 7.73-7.90 (1H, m)

[0585] The compound of Reference Example 43 1H-NMR (250 MHz, CDCl3) δ ppm: 1.42 (3H, t, J=7.1 Hz), 4.41 (2H, q, J=7.1 Hz), 7.27-7.90 and 8.02-8.22 (all 13H, m)

[0586] The compound of Reference Example 44 1H-NMR (200 MHz, CDCl3) δ ppm: 1.37 (3H, t, J=7.1 Hz), 4.34 (2H, q, J=7.1 Hz), 7.01-7.31 and 7.32-7.68 (all 11H, m), 7.79-8.00 (2H, m)

[0587] The compound of Reference Example 45 1H-NMR (200 MHz, CDCl3) δ ppm: 1.47 (3H, t, J=7 Hz), 4.41 (2H, q, J=7 Hz), 7.29-7.57, 7.58-7.84 and 8.03-8.21 (all 13H, m)

[0588] The compound of Reference Example 46 1H-NMR (200 MHz, CDCl3) δ ppm: 2.42 (3H, s), 2.67 (3H, s), 3.91 (3H, s), 7.07-7.59 (6H, m), 7.87-8.11 (1H, m)

[0589] The compound of Reference Example 47 1H-NMR (200 MHz, CDCl3) δ ppm: 3.91, 3.94, 3.97 and 3.98 (each 3H, each s), 6.96 (1H, d, J=8.3 Hz), 7.03-7.24 (4H, m), 7.88 (1H, d, J=7.9 Hz)

[0590] The compound of Reference Example 48 1H-NMR (200 MHz, CDCl3) δ ppm: 2.43, 3.91 and 3.98 (each 3H, each s), 7.04-7.29 (3H, m), 7.30-7.51 (3H, m), 7.88 (1H, d, J=7.9 Hz)

[0591] The compound of Reference Example 49 1H-NMR (200 MHz, CDCl3) δ ppm: 2.67 (3H, s), 3.86 (3H, s), 3.90 (3H, s), 6.90-7.08 (2H, m), 7.35-7.49 (2H, m) and 7.50-7.66 (2H, m), 7.89-8.07 (1H, m)

[0592] The compound of Reference Example 50 1H-NMR (200 MHz, CDCl3) δ ppm: 2.69 (3H, s), 3.92 (3H, s), 7.27-7.81 and 7.95-8.11 (all 12H, m)

[0593] The compound of Reference Example 51 1H-NMR (200 MHz, CDCl3) δ ppm: 2.12 (3H, s), 3.82 (3H, s), 3.95 (3H, s), 7.02-7.48 (5H, m), 7.63 (1H, d, J=1.4 Hz), 7.71 (1H, dd, J=7.7 Hz, J=1.4 Hz)

[0594] The compound of Reference Example 52

[0595]

1
H-NMR (200 MHz, CDCl3) δ ppm: 2.05 (3H, s), 3.77 (6H, s), 3.96 (3H, s), 7.03-7.18 (1H, m), 7.19-7.32 (3H, m), 7.34 (2H, s)

[0596] The compound of Reference Example 53 1H-NMR (200 MHz, CDCl3) δ ppm: 2.40, 3.90 and 3.97 (each 3H, each s), 7.09-7.34 (4H, m), 7.42-7.59 (2H, m), 7.87 (1H, d, J=7.9 Hz)

[0597] The compound of Reference Example 54 1H-NMR (200 MHz, CDCl3) δ ppm: 2.26, 2.65 and 3.91 (each 3H, each s), 7.08-7.38 (6H, m), 7.89-8.02 (1H, m)

[0598] The compound of Reference Example 55 1H-NMR (200 MHz, CDCl3) δ ppm: 2.41 and 3.93 (each 3H, each s), 7.17-7.34 (2H, m), 7.46-7.57 (2H, m), 7.82-7.72 (2H, m), 8.02-8.16 (2H, m)

[0599] The compound of Reference Example 56

[0600]

1
H-NMR (200 MHz, CDCl3) δ ppm: 2.26 and 3.94 (each 3H, each s), 7.14-7.35 (4H, m), 7.36-7.52 (2H, m), 7.99-8.18 (2H, m)

[0601] The compound of Reference Example 57

[0602]

1
H-NMR (200 MHz, CDCl3) δ ppm: 2.68 (3H, s), 3.91 (3H, s), 7.29-7.54 and 7.55-7.72 (all 7H, m), 7.91-8.08 (1H, m)

[0603] The compound of Reference Example 58 1H-NMR (200 MHz, CDCl3) δ ppm: 2.04 (6H, s), 3.88 and 3.92 (each 3H, each s), 6.71-6.85 (2H, m), 7.06-7.48 (3H, m), 7.78-7.93 (1H, m)

[0604] The compound of Reference Example 59

[0605]

1
H-NMR (200 MHz, CDCl3) δ ppm: 2.66 (3H, s), 3.90 (3H, s), 5.12 (2H, s), 6.98-7.12 (2H, m), 7.20-7.68 (10H, m)

[0606] The compound of Reference Example 60 1H-NMR (200 MHz, CDCl3) δ ppm: 2.70 (3H, s), 3.93 (3H, s), 7.38-7.58 (2H, m), 7.68-7.87 (2H, m), 7.98-8.12 (1H, m), 8.21-8.46 (2H, m)

[0607] The compound of Reference Example 61 1H-NMR (200 MHz, CDCl3) δ ppm: 1.42 (3H, t, J=7.0 Hz), 4.42 (2H, q, J=7.0 Hz), 7.28-7.78 and 7.85-8.18 (all 8H, m)

[0608] The compound of Reference Example 62 1H-NMR (200 MHz, CDCl3) δ ppm: 2.40 (3H, s), 2.67 (3H, s), 3.90 (3H, s), 7.18-7.31 (2H, m), 7.37-7.58 (4H, m), 7.91-8.05 (1H, m)

[0609] The compound of Reference Example 63 1H-NMR (200 MHz, CDCl3) δ ppm: 1.44 (3H, t, J=7.0 Hz), 2.66 (3H, s), 3.90 (3H, s), 4.10 (2H, q, J=7.0 Hz), 6.88-7.06 (2H, m), 7.34-7.49 (2H, m), 7.50-7.64 (2H, m), 7.89-8.06 (1H, m)

[0610] The compound of Reference Example 64 1H-NMR (200 MHz, CDCl3) δ ppm: 1.06 (3H, t, J=7.4 Hz), 1.70-1.97 (2H, m), 2.66 (3H, m), 3.97 (2H, d, J=6.5 Hz), 6.89-7.08 (2H, m), 7.35-7.48 (2H, m), 7.49-7.64 (2H, m), 7.89-8.08 (1H, m)

[0611] The compound of Reference Example 65 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.40-2.90 and 3.21-3.90 [all 13H, m, 2.33 (s)], 6.50-8.40 [all 4H, m, 7.71 (d, J=8.41 Hz)]

[0612] The compound of Reference Example 66 1H-NMR (200 MHz, CDCl3) δ ppm: 2.85-4.90 (all 9H, m), 6.79-7.38 and 7.45-7.69 (all 7H, m)

[0613] The compound of Reference Example 68 1H-NMR (200 MHz, DMSO-d6) δ ppm: 2.60-4.75 (all 11H, m), 6.80-7.85 [all 8H, m, 7.77 (d, J=8.80 Hz)]

[0614] The compound of Reference Example 70 1H-NMR (200 MHz, CDCl3) δ ppm: 2.74 (3H, s), 3.88 (3H, s), 5.82-8.39 [all 8H, m, 6.95 (d, J=8.0 Hz), 8.15 (d, J=8.52 Hz)]

[0615] The compound of Reference Example 75 1H-NMR (200 MHz, DMSO-d6) δ ppm: 2.77 (3H, s), 3.42-3.50 (2H, m), 3.78-3.86 (2H, m), 7.49 (1H, dd, J=8.8 Hz, J=2.2 Hz), 7.83 (1H, d, J=8.8 Hz), 7.84 (1H, d, J=2.2 Hz), 12.6-13.3 (1H, m)

[0616] The compound of Reference Example 76 1H-NMR (200 MHz, DMSO-d6) δ ppm: 0.86 (6H, d, J=6.6 Hz), 1.8-2.05 (1H, m), 3.0 (2H, d, J=7.2 Hz), 3.4-3.55 (2H, m), 3.8-3.95 (2H, m), 7.49 (1H, dd, J=8.8 Hz, J=2.2 Hz), 7.83 (1H, d, J=8.8 Hz), 7.85 (1H, d, J=2.2 Hz), 12.8-13.1 (1H, m)

[0617] The compound of Reference Example 77 1H-NMR (200 MHz, DMSO-d6) δ ppm: 3.3-3.41 (2H, m), 3.75-3.95 (2H, m), 4.39 (2H, s), 7.2-7.45 (5H, m), 7.5 (1H, dd, J=9 Hz, J=2.2 Hz), 7.84 (1H, d, J=9 Hz), 7.88 (1H, d, J=2.2 Hz)

[0618] The compound of Reference Example 78 1H-NMR (200 MHz, DMSO-d6) δ ppm: 2.93 (3H, s), 4.56 (2H, s), 7.20-7.50 (5H, m), 7.62 (2H, d, J=8.7 Hz), 7.81 (2H, d, J=8.7 Hz), 8.76 (1H, s)

[0619] The compound of Reference Example 79 1H-NMR (200 MHz, DMSO-d6) δ ppm: 7.38-7.51 (1H, m), 7.51-7.95 (4H, m), 7.95-8.10 (1H, m), 8.68-8.95 (2H, m), 10.3-13.5 (1H, br)

[0620] The compound of Reference Example 80 1H-NMR (200 MHz, DMSO-d6) δ ppm: 2.58 (3H, s), 7.38-7.48 (2H, m), 7.48-7.64 (1H, m), 7.46-8.01 (1H, m), 8.63 (1H, d, J=5.0 Hz), 8.80 (1H, s)

[0621] The compound of Reference Example 81 1H-NMR (200 MHz, DMSO-d6) δ ppm: 2.22 (3H, s), 2.30-2.58 (4H, m), 3.15-3.40 (4H, m), 6.85-7.05 (2H, m), 7.15-7.84 (2H, m), 11.75-12.80 (1H, brs)

[0622] The compound of Reference Example 94 1H-NMR (200 MHz, DMSO-d6) δ ppm: 0.77 (3H, t, J=7.3 Hz), 1.75 (2H, q, J=7.3 Hz), 4.15 (2H, t, J=7.3 Hz), 7.31-7.97 (3H, m), 8.02 (1H, d, J=1.7 Hz), 8.11-8.27 (2H, m)

[0623] The compound of Reference Example 95 1H-NMR (200 MHz, DMSO-d6) δ ppm: 7.19 (1H, s), 7.35-7.64 (2H, m), 7.69 (1H, s), 8.00-8.30 (4H, m), 10.40-11.62 (1H, brs)

[0624] The compound of Reference Example 98 1H-NMR (200 MHz, CDCl3) δ ppm: 1.55-1.94 (4H, m), 2.13-2.30 (2H, m), 2.31-2.56 (2H, m), 2.66 (3H, s), 6.18-6.35 (1H, m), 7.15-7.42 (2H, m), 7.90-8.18 (1H, m)

[0625] The compound of Reference Example 99 1H-NMR (200 MHz, DMSO-d6) δ ppm: 2.62 (3H, s), 7.58-7.82 (2H, m), 7.88-8.19 (3H, m), 8.21-8.48 (2H, m), 12.97 (1H, s)

[0626] The compound of Reference Example 102 1H-NMR (200 MHz, CDCl3) δ ppm: 1.42-2.00 (6H, m), 2.18-2.46 (2H, m), 2.47-2.79 (3H, s), 6.21 (1H, t, J=6.7 Hz), 7.05-7.40 (1H, m), 7.88-8.12 (1H, m)

[0627] The compound of Reference Example 111 1H-NMR (200 MHz, CDCl3) δ ppm: 7.03-7.31 (7H, m), 7.32-7.58 (4H, m), 7.95 (2H, d, J=8.35 Hz)

[0628] The compound of Reference Example 113 1H-NMR (200 MHz, CDCl3) δ ppm: 2.30 and 4.15 (each 3H, each s), 7.09-7.48 (6H, m), 8.23 (1H, d, J=8.1 Hz), 10.0-11.42 (1H, m)

[0629] The compound of Reference Example 114 1H-NMR (200 MHz, CDCl3) δ ppm: 2.73 and 3.87 (each 3H, each s), 7.00 and 7.59 (each 2H, each dd, J=8.8 Hz, J=2.1 Hz), 7.36-7.52 (2H, m), 8.03-8.21 (1H, m)

[0630] The compound of Reference Example 116 1H-NMR (200 MHz, CDCl3) δ ppm: 2.14 and 3.85 (each 3H, each s), 7.09-7.41 (5H, m), 7.71 (1H, d, J=1.4 Hz), 7.82 (1H, dd, J=8.0 Hz, J=1.5 Hz)

[0631] The compound of Reference Example 120 1H-NMR (200 MHz, CDCl3) δ ppm: 1.21-2.06 and 2.48-2.82 (all 13H, m), 2.63 (3H, s), 4.84-6.49 (1H, m), 6.98-7.19 (2H, m), 7.99 (1H, d, J=8.7 Hz)

[0632] The compound of Reference Example 121 1H-NMR (200 MHz, CDCl3) δ ppm: 1.40-2.23 and 2.87-3.14 (all 9H, m), 2.64 (3H, s), 6.98-7.24 (2H, m), 8.00 (1H, d, J=8.7 Hz)

[0633] The compound of Reference Example 122 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.49-1.88 (4H, m), 2.08-2.19 and 2.20-2.52 (each 2H, each m), 6.20-6.40 (1H, m), 7.51 and 7.87 (each 2H, each d, each J=8.4 Hz), 12.42-13.18 (1H, m)

[0634] The compound of Reference Example 123 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.49-1.68 (4H, m), 1.69-1.91 (2H, m), 2.18-2.37 (2H, m), 2.45-2.67 (2H, m), 6.23 (1H, t,J=6.7 Hz), 7.42 and 7.86 (each 2H, each d, each J=8.4 Hz), 7.28-7.79 (1H, m)

[0635] The compound of Reference Example 129 1H-NMR (200 MHz, CDCl3) δ ppm: 2.75 (3H, m), 7.29-7.74 (7H, m), 8.10-8.22 (1H, m)

[0636] The compound of Reference Example 153 1H-NMR (200 MHz, CDCl3) δ ppm: 3.94 (s, 3H), 7.58 (dd, J=8.6, 2.2 Hz, 1H), 7.78 (d, J=2.2 Hz, 1H), 7.90 (d, J=8.6 Hz, 1H), 8.32 (1H, brs)

[0637] The compound of Reference Example 145 1H-NMR (200 MHz, CDCl3) δ ppm: 2.70 (3H, s), 3.92 (3H, s), 7.22-7.35 (1H, m), 7.70-7.96 (4H, m), 8.03 (1H, d, J=8.2 Hz), 8.67-8.78 (1H, m)

[0638] The compound of Reference Example 157 1H-NMR (200 MHz, CDCl3) δ ppm: 2.88 (3H, s), 3.41-3.50 (2H, m), 3.79-3.89 3.89 (3H, s), 3.90 (3H, s), 7.49 (1H, d, J=8.2 Hz), 7.87 (1H, d, J=1.7 Hz), 7.65 (1H, dd, J=8.2 Hz, 1.7 Hz)

[0639] The compound of Reference Example 158 1H-NMR (200 MHz, CDCl3) δ ppm: 3.77, 3.83, 3.93 (each 3H, eash s), 6.89-7.08 (2H, m), 7.15-7.44 (3H, m), 7.54-7.79 (2H, m)

[0640] The compound of Reference Example 159 1H-NMR (200 MHz, CDCl3) δ ppm: 3.84, 3.88, 3.94 (each 3H, each s), 6.83-6.98 (1H, m), 7.02-7.15 (2H, m), 7.27-7.43 (2H, m), 7.64 (1H, d, J=1.4 Hz), 7.71 (1H, dd, J=1.6 Hz, J=7.8 Hz)

[0641] The compound of Reference Example 162 1H-NMR (200 MHz, DMSO-d6) δ ppm: 2.55 (3H, s), 4.53 (2H, s), 4.55 (2H, s), 7.25-7.55 (7H, m), 7.88 (1H, d, J=9 Hz), 12.88 (1H, s)

[0642] The compound of Reference Example 163 1H-NMR (200 MHz, DMSO-d6) δ ppm: 2.62 (3H, s), 7.70-7.82 (1H, m), 7.90-8.13 (3H, m), 8.20-8.40 (2H, m), 8.72-8.86 (1H, m)

[0643] The compound of Reference Example 170 1H-NMR (200 MHz, CDCl3) δ ppm: 0.97 (6H, d, J=6.6 Hz), 1.23 (3H, t, J=7.0 Hz), 1.85-2.10 (1H, m), 3.13 (2H, d, J=7.5 Hz), 3.39 (2H, q, J=7 Hz), 6.54 (1H, s), 7.36 (1H, dd, J=8.7 Hz, J=2.2 Hz), 7.63 (1H, d, J=2.2 Hz), 7.98 (1H, d, J=8.7 Hz)

[0644] The compound of Reference Example 171 1H-NMR (200 MHz, DMSO-d6) δ ppm: 2.57 (3H, s), 5.17 (2H, s), 6.58-6.92, 6.93-8.03 (total 12H, m), 12.56-12.94 (1H, m)

[0645] The compound of Reference Example 173 1H-NMR (250 MHz, DMSO-d6) δ ppm: 2.84 (2H, t, J=4.6 Hz), 3.70 (2H, t, J=4.6 Hz), 4.64 (2H, s), 7.17 (4H, s), 7.54 (1H, dd, J=7 Hz, J=1.6 Hz), 7.76-7.83 (2H, m), 9.01 (1H, s)

[0646] The compound of Reference Example 175 1H-NMR (200 MHz, DMSO-d6) δ ppm: 2.61 (3H, s), 4.10-5.40 (2H, brs), 7.32-7.90 (4H, m), 7.95 (1H, d, J=8.2 Hz), 9.22 (1H, d, J=5.8 Hz)

[0647] The compound of Reference Example 176 1H-NMR (200 MHz, DMSO-d6) δ ppm: 2.86 (2H, t, J=5.8 Hz), 3.67 (2H, t, J=5.8 Hz), 3.89 (3H, s), 4.63 (2H, s), 7.18 (4H, s), 7.4-7.95 (1H, d, J=8.2 Hz)

[0648] The compound of Reference Example 174 1H-NMR (200 MHz, DMSO-d6) δ ppm: 0.83 (6H, d, J=6.6 Hz), 1.68-1.97 (1H, m), 2.42 (2H, d, J=7.2 Hz), 2.48 (3H, s), 6.93-7.13 (2H, m), 7.74 (1H, d, J=8.5 Hz)

[0649] The compound of Reference Example 146 1H-NMR (200 MHz, CDCl3) δ ppm: 1.92-2.18, 3.21-3.45 (total 8H, m), 3.85 (3H, s), 6.38 (1H, dd, J=2.5 Hz, J=2.45 Hz), 7.88 (1H, d, J=11.3 Hz)

[0650] The compound of Reference Example 147 1H-NMR (200 MHz, CDCl3) δ ppm: 3.29 (4H, t, J=4.8 Hz), 3.84 (4H, t, J=5.1 Hz), 3.87 (3H, s), 6.73 (1H, dd, J=2.8 Hz, J=2.6 Hz), 6.86 (1H, d, J=2.7 Hz), 7.85 (1H, d, J=9.0 Hz)

[0651] The compound of Reference Example 161 1H-NMR (200 MHz, CDCl3) δ ppm: 0.79-1.02 (9H, m with s at 0.96), 1.59 (2H, t, J=7.8 Hz), 3.86 (3H, s), 3.89 (3H, s), 4.23 (2H, t, J=7.5 Hz), 6.90 (1H, dd, J=8.5 Hz, J=8.5 Hz), 7.03 (1H, s), 7.43 (1H, d, J=1.7 Hz), 7.80 (1H, d, J=8.5 Hz)

[0652] The compound of Reference Example 164 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.85-2.12 (4H, m), 3.12-3.46 (4H, m), 6.35-6.62 (2H, m), 7.74 (1H, d, J=8.6 Hz), 12.35 (1H, brs)

[0653] The compound of Reference Example 165 1H-NMR (200 MHz, DMSO-d6) δ ppm: 3.25 (4H, t, J=5.0 Hz), 3.70 (4H, t, J=5.0 Hz), 6.80-7.09 (2H, m), 7.75 (1H, d, J=8.7 Hz)

[0654] The compound of Reference Example 180 1H-NMR (200 MHz, DMSO-d6) δ ppm: 0.93 (9H, s), 1.55 (2H, t, J=7.5 Hz), 3.76 (3H, s), 4.15 (2H, t, J=7.4 Hz), 7.05 (1H, dd, J=8.6 Hz, J=8.6 Hz), 7.34 (1H, d, J=1.6 Hz), 7.64 (1H, d, J=8.9 Hz), 9.88 (1H, s)

[0655] The compound of Reference Example 148 1H-NMR (200 MHz, CDCl3) δ ppm: 2.60 (3H, s), 3.85 (3H, s), 5.09 (2H, s), 6.72-6.99 [2H, m, (6.83,1H, s)], 7.25-7.48 (5H, m), 7.93 (1H, d, J=9.1 Hz)

[0656] The compound of Reference Example 150 1H-NMR (200 MHz, CDCl3) δ ppm: 1.35 (6H, d, J=6.1 Hz), 2.59 (3H, s), 3.85 (3H, s), 4.49-4.71 (1H, m), 6.61-6.78 (2H, m), 7.82-7.98 (1H, m)

[0657] The compound of Reference Example 151 1H-NMR (200 MHz, CDCl3) δ ppm: 0.98 (3H, t, J=7.8 Hz), 1.30-1.89 (4H, m), 2.59 (3H, s), 3.85 (3H, s), 4.13 (2H, t, J=6.5 Hz), 6.68-6.80 (2H, m), 7.83-7.99 (1H, m)

[0658] The compound of Reference Example 152 1H-NMR (200 MHz, CDCl3) δ ppm: 1.03 (6H, d, J=6.7 Hz), 1.98-2.21 (1H, m), 2.59 (3H, s), 3.75 (2H, d, J=6.6 Hz), 3.85 (3H, s), 6.66-6.81 (2H, m), 7.82-7.99 (1H, m)

[0659] The compound of Reference Example 154 1H-NMR (200 MHz, DMSO-d6) δ ppm: 2.50 (3H, s), 3.78 (3H, s), 4.75 (2H, s), 6.73-6.93 (2H, m), 7.82 (1H, d, J=8.5 Hz), 13.09 (1H, brs)

[0660] The compound of Reference Example 167 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.26 (6H, d, J=6.0 Hz), 2.49 (3H, s), 4.56-4.80 (1H, m), 6.69-6.85 (2H, m), 7.75-7.85 (1H, m), 12.39 (1H, s)

[0661] The compound of Reference Example 168 1H-NMR (200 MHz, DMSO-d6) δ ppm: 0.93 (3H, t, J=7.3 Hz), 1.33-1.55 (2H, m), 1.57-1.81 (2H, m), 2.51 (3H, s), 4.01 (2H, t, J=6.4 Hz), 6.72-6.90 [2H, m, (6.83 (1H, s))], 7.82 (1H, d, J=7.6 Hz), 12.41 (1H, s)

[0662] The compound of Reference Example 169 1H-NMR (200 MHz, DMSO-d6) δ ppm: 0.96 (6H, d, J=6.7 Hz), 1.87-2.15 (1H, m),2.50 (3H, s), 3.78 (2H, d, J=6.5 Hz), 6.72-6.88 [2H, m, 6.82 (1H, s)], 7.81 (1H, d, J=7.8 Hz), 12.40 (1H, brs)

Example 1

[0663] 4-Ethoxy-2-methoxybenzoic acid (0.33 g) is dissolved in thionyl chloride (10 ml), and the mixture is refluxed for 30 minutes. The mixture is concentrated under reduced pressure, and thereto is added toluene (20 ml), and the mixture is concentrated again under reduced pressure. The resulting 4-ethoxy-2-methoxybenzoyl chloride is dissolved in dichloromethane (10 ml), and the mixture is cooled at 0° C. over an ice-bath, and thereto is added 7-chloro-5-[N-methyl-N-(2-diethylaminoethyl)amino]carbonylmethyl-2,3,4,5-tetrahydro-1H-benzazepine (0.5 g). To the mixture is added triethylamine (0.6 ml), and the mixture is stirred at the same temperature for two hours. To the reaction solution is added water, and the mixture is extracted with dichloromethane. The extract is dried over sodium carbonate, and purified by silica gel column chromatography (solvent; dichloromethane:methanol=50:1˜5:1). The resulting oily product is dissolved in ethanol, and thereto is added conc. hydrochloric acid (0.1 ml), and the mixture is concentrated under reduce pressure to give 7-chloro-5-[N-methyl-N-(2-diethylaminoethyl)amino]carbonylmethyl-1-(2-methoxy-4-ethoxybenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine hydrochloride (0.2 g) in a colorless amorphous.

[0664]

1
H-NMR (200 MHz, DMSO-d6) δ ppm: 0.98-2.06 (13H, m), 2.61-4.88 (21H, m), 6.18-7.45 (6H, m), 10.42-11.52 (1H, m)

Example 2

[0665] To 4-cyclohexylbenzoic acid (2 g) is added thionyl chloride (20 ml), and the mixture is refluxed for two hours. The mixture is evaporated to remove the thionyl chloride to give 4-cyclohexylbenzoyl chloride. To a solution of 5-ethoxycarbonylmethyl-7-chloro-2,3,4,5-tetrahydro-1H-benzazepine (2.2 g) in dichloromethane (50 ml) is added pyridine (3.3 g), and to the mixture is added with stirring the above obtained 4-cyclohexylbenzoyl chloride under ice-cooling, and the mixture is stirred at room temperature overnight. To the reaction solution is added water, and the mixture is extracted with dichloromethane. The extract is washed with diluted hydrochloric acid, and washed with water, and dried over magnesium sulfate. The mixture is evaporated to remove the solvent, and the residue is purified by silica gel column chromatography (solvent; dichloromethane) to give 5-ethoxycarbonylmethyl-7-chloro-1-(4-cyclohexylbenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (4 g) as colorless oil.

[0666]

1
H-NMR (200 MHz, CDCl3) δ ppm: 1.27 (3H, t, J=7.1 Hz), 1.20-2.20 (14H, m), 2.30-2.50 (1H, m), 2.60-3.05 (3H, m), 3.10-3.35 (1H, m), 4.10-4.40 (2H, m), 4.45-4.65 (1H, m), 6.57 (1H, d, J=8.4 Hz), 6.96 (1H, d, J=8.1 Hz), 7.00 (2H, d, J=8.0 Hz), 7.10-7.35 (3H, m)

Example 3

[0667] To a solution of 5-ethoxycarbonylmethyl-7-chloro-1-(4-cyclohexylbenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (2 g) in ethanol (20 ml) is added a 5N aqueous sodium hydroxide solution (5 ml), and the mixture is stirred at room temperature overnight. The reaction solution is acidified with hydrochloric acid, and the mixture is extracted with dichloromethane. The extract is washed with water, dried over magnesium sulfate, and evaporated to remove the solvent to give 5-carboxymethyl-7-chloro-1-(4-cyclohexylbenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (1.8 g) in colorless amorphous.

[0668]

1
H-NMR (200 MHz, CDCl3) δ ppm: 1.20-2.25 (14H, m), 2.30-2.55 (1H, m), 2.60-3.30 (3H, m), 3.50-3.90 (1H, m), 4.45-4.60 and 5.10-5.30 (1H, m), 6.15 (1H, brs), 6.59 (1H, d, J=8.3 Hz), 6.85-7.00 (3H, m), 7.10-7.35 (3H, m)

[0669] The starting compounds are treated in the same manner as Example 3 to give the compounds of Examples 52, 68, 77, 78, 81-83, 87, 90, 96, 101, 103, 104, 109, 117-118, 120 and 131-135.

Example 4

[0670] To a solution of 5-carboxymethyl-7-chloro-1-(4-cyclohexylbenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (0.7 g) in dichloromethane (50 ml) is added with stirring N,N-bis(2-oxo-3-oxazolidinyl)phosphinic chloride (0.54 g) under ice-cooling, and the mixture is stirred at room temperature for 15 minutes. To the mixture are added with stirring N-methylpiperazine (0.24 ml) and triethylamine (0.46 ml) under ice-cooling, and the mixture is stirred at room temperature overnight. To the reaction solution is added water, and the mixture is extracted with dichloromethane. The extract is washed with water, dried over magnesium sulfate, and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; dichloromethane:methanol=40:1) to give 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-(4-cyclohexylbenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (0.7 g) as colorless amorphous.

[0671]

1
H-NMR (200 MHz, CDCl3) δ ppm: 1.20-3.40 (22H, m), 2.21 and 2.34 (3H, s), 3.50-3.90 (5H, m), 4.40-4.60 and 5.05-5.20 (1H, m), 6.50-6.60 (1H, m), 6.85-6.95 (1H, m), 7.00-7.15 (3H, m), 7.25-7.50 (2H, m)

[0672] The suitable starting compounds are treated in the same manner as in Example 4 to give the compounds of Examples 7, 9, 11-18, 20-22, 24, 25, 28-36, 38-40, 46-48, 55-67, 70-72, 74-76, 79, 84, 85, 88, 91-94, 98, 121-126, 137 and 138.

Example 5

[0673] 7-Chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-{4-[2-(2-methylphenyl)acetyl]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine (2.06 g) is dissolved in a mixture of methylene chloride (20 ml) and methanol (20 ml), and thereto is added with stirring sodium borohydride (0.28 g) under cooling over an ice-bath. The mixture is stirred for two hours over an ice-bath, and the mixture is evaporated to remove almost of the solvent. To the residue is added water, and the mixture is extracted with methylene chloride. The organic layer is washed with a saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated. The residue is purified by silica gel column chromatography (solvent; methylene chloride:methanol=20˜10:1) to give 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-{4-[2-(2-methylphenyl)-1-hydroxyethyl]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine (2.08 g) as colorless amorphous.

[0674]

1
H-NMR (200 MHz, CDCl3) δ ppm: 1.1-4.0, 4.35-4.65, 4.65-5.0 and 5.0-5.25 (all 27H, m), 6.4-6.65 (1H, m), 6.75-7.6 (10H, m)

[0675] The suitable starting compounds are treated in the same manner as in Example 5 to give the compounds of Examples 22, 46 and 94.

Example 6

[0676] To a mixture of 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-{4-[2-(2-methylphenyl)-1-hydroxyethyl]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine (0.5 g), acetic acid (5 ml) and acetic anhydride (3 ml) is added a drop of conc. sulfuric acid, and the mixture is stirred at room temperature for 12 hours, and subsequently stirred at a temperature from 60-70° C. for 6 hours. The reaction mixture is poured into ice-water, and thereto is added ethyl acetate (30 ml). The mixture is basified with sodium hydrogen carbonate, and extracted with ethyl acetate. The organic layer is washed successively with a saturated aqueous sodium hydrogen carbonate solution and a saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated. The residue is purified by silica gel column chromatography (solvent; methylene chloride:methanol=20:1) to give 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-{4-[2-(2-methylphenyl)-1-acetyloxyethyl]-benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine (0.36 g) as colorless amorphous.

[0677]

1
H-NMR (200 MHz, CDCl3) δ ppm: 1.1-4.0, 4.35-4.7 and 4.95-5.25 (all 28H, m), 5.7-6.0 (1H, m), 6.4-6.65 (1H, m), 6.75-7.6 (10H, m)

[0678] The suitable starting compounds are treated in the same manner as in Example 6 to give the compounds of Examples 12 and 48.

[0679] The suitable starting compounds are treated in the same manner as in Examples 1 and 2 to give the following compounds.

249

Example 7Structure:

250

X: —CH2—R1: 7-Cl

251

R3: HCrystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 146-148° C.Form: FreeExample 8Structure:

252

X: —CH2—R1: 7-Cl

253

R3: HCrystalline form: White powderSolvent for recrystallization: Acetone/diethyl etherM.p. 184-186° C.Form: FreeExample 9Structure:

254

X: —CH2—R1: 7-Cl

255

R3: HCrystalline form: Colorless amorphousNMR analysis: 1)Form: FreeExample 10Structure:

256

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousNMR analysis: 2)Form: FreeExample 11Structure:

257

X: —CH2—R1: 7-Cl

258

R3: HCrystalline form: Colorless amorphousNMR analysis: 3)Form: FreeExample 12Structure:

259

X: —CH2—R1: 7-Cl

260

R3: HCrystalline form: Colorless amorphousNMR analysis: 4)Form: HydrochlorideExample 13Structure:

261

X: —CH2—R1: 7-Cl

262

R3: HCrystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 186-187° C.Form: FreeExample 14Structure:

263

X: —CH2—R1: 7-Cl

264

R3: HCrystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 162-162.5° C.Form: FreeExample 15Structure:

265

X: —CH2—R1: 7-Cl

266

R3: HCrystalline form: Colorless amorphousNMR analysis: 5)Form: FreeExample 16Structure:

267

X: —CH2—R1: 7-Cl

268

R3: HCrystalline form: Colorless amorphousNMR analysis: 6)Form: FreeExample 17Structure:

269

X: —CH2—R1: 7-Cl

270

R3: HCrystalline form: Colorless needlesSolvent for recrystallization: EthanolM.p. 181-182.5° C.Form: FreeExample 18Structure:

271

X: —CH2—R1: 7-Cl

272

R3: HCrystalline form: Colorless needlesSolvent for recrystallization: Ethanol/diethyl etherM.p. 123-126° C.Form: FreeExample 19Structure:

273

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Colorless platesSolvent for recrystallization: Dichloromethane/n-hexaneM.p. 87.5-88° C.Form: FreeExample 20Structure:

274

X: —CH2—R1: 7-Cl

275

R3: HCrystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 152-153° C.Form: FreeExample 21Structure:

276

X: —CH2—R1: 7-Cl

277

R3: HCrystalline form: Colorless amorphousNMR analysis: 7)Form: FreeExample 22Structure:

278

X: —CH2—R1: 7-Cl

279

R3: HCrystalline form: Colorless amorphousNMR analysis: 8)Form: FreeExample 23Structure:

280

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Colorless amorphousNMR analysis: 9)Form: FreeExample 24Structure:

281

X: —CH2—R1: 7-Cl

282

R3: HCrystalline form: Colorless amorphousNMR analysis: 79)Form: FreeExample 25Structure:

283

X: —CH2—R1: 7-Cl

284

R3: HCrystalline form: Pale yellow amorphousNMR analysis: 10)Form: FreeExample 26Structure:

285

X: —CH2—R1: 7-ClR2: H R3: HCrystalline form: Colorless amorphousNMR analysis: 11)Form: FreeExample 27Structure:

286

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Colorless oilNMR analysis: 12)Form: FreeExample 28Structure:

287

X: —CH2—R1: 7-Cl

288

R3: HCrystalline form: Colorless amorphousNMR analysis: 13)Form: FreeExample 29Structure:

289

X: —CH2—R1: 7-Cl

290

R3: HCrystalline form: Colorless amorphousNMR analysis: 14)Form: HydrochlorideExample 30Structure:

291

X: —CH2—R1: 7-Cl

292

R3: HCrystalline form: Colorless amorphousNMR analysis: 15)Form: HydrochlorideExample 31Structure:

293

X: —CH2—R1: 7-Cl

294

R3: HCrystalline form: Colorless amorphousNMR analysis: 16)Form: HydrochlorideExample 32Structure:

295

X: —CH2—R1: 7-Cl

296

R3: HCrystalline form: Colorless amorphousNMR analysis: 17)Form: HydrochlorideExample 33Structure:

297

X: —CH2—R1: 7-ClR2: —CH2CONH2R3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherM.p. 104-108° C.Form: FreeExample 34Structure:

298

X: —CH2—R1: 7-Cl

299

R3: HCrystalline form: Colorless amorphousNMR analysis: 18)Form: FreeExample 35Structure:

300

X: —CH2—R1: 7-Cl

301

R3: HCrystalline form: Colorless amorphousNMR analysis: 19)Form: FreeExample 36Structure:

302

X: —CH2—R1: 7-Cl

303

R3: HCrystalline form: Colorless amorphousNMR analysis: 20)Form: FreeExample 37Structure:

304

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Colorless prismsSolvent for recrystallization: Ethyl acetate/diethyl ether/n-hexaneM.p. 145-147° C.Form: FreeExample 38Structure:

305

X: —CH2—R1: 7-Cl

306

R3: HCrystalline form: Colorless amorphousNMR analysis: 21)Form: FreeExample 39Structure:

307

X: —CH2—R1: 7-Cl

308

R3: HCrystalline form: Colorless amorphousNMR analysis: 22)Form: FreeExample 40Structure:

309

X: —CH2—R1: 7-Cl

310

R3: HCrystalline form: Pale yellow viscous oilNMR analysis: 23)Form: FreeExample 41Structure:

311

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 133-133.5° C.Form: FreeExample 42Structure:

312

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Acetone/diethyl etherM.p. 135° C.Form: FreeExample 43Structure:

313

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Acetone/diethyl etherM.p. 133° C.Form: FreeExample 44Structure:

314

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Acetone/diethyl etherM.p. 154° C.Form: FreeExample 45Structure:

315

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Acetone/diethyl etherM.p. 166° C.Form: FreeExample 46Structure:

316

X: —CH2—R1: 7-Cl

317

R3: HCrystalline form: Colorless amorphousNMR analysis: 24)Form: FreeExample 47Structure:

318

X: —CH2—R1: 7-Cl

319

R3: HCrystalline form: Colorless amorphousNMR analysis: 25)Form: DihydrochlorideExample 48Structure:

320

X: —CH2—R1: 7-Cl

321

R3: HCrystalline form: Colorless amorphousNMR analysis: 26)Form: FreeExample 49Structure:

322

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Colorless amorphousNMR analysis: 27)Form: FreeExample 50Structure:

323

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Colorless amorphousNMR analysis: 28)Form: HydrochlorideExample 51Structure:

324

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Yellow platesSolvent for recrystallization: Acetone/diethyl etherM.p. 125° C.Form: FreeExample 52Structure:

325

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousNMR analysis: 80)Form: FreeExample 53Structure:

326

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White platesSolvent for recrystallization: Ethanol/diethyl etherM.p. 230-232° C.Form: FreeExample 54Structure:

327

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Colorless oilNMR analysis: 81)Form: FreeExample 55Structure:

328

X: —CH2—R1: 7-Cl

329

R3: HCrystalline form: Colorless amorphousNMR analysis: 82)Form: HydrochlorideExample 56Structure:

330

X: —CH2—R1: 7-ClR2: —CH2CONH(CH2)2N(C2H5)2R3: HCrystalline form: Colorless amorphousNMR analysis: 83)Form: HydrochlorideExample 57Structure:

331

X: —CH2—R1: 7-Cl

332

R3: HCrystalline form: Colorless amorphousNMR analysis: 84)Form: HydrochlorideExample 58Structure:

333

X: —CH2—R1: 7-ClR2: —CH2CONH(CH2)2N(C2H5)2R3: HCrystalline form: Colorless amorphousNMR analysis: 85)Form: HydrochlorideExample 59Structure:

334

X: —CH2—R1: 7-Cl

335

R3: HCrystalline form: Colorless viscous oilNMR analysis: 29)Form: FreeExample 60Structure:

336

X: —CH2—R1: 7-Cl

337

R3: HCrystalline form: Colorless viscous oilNMR analysis: 30)Form: FreeExample 61Structure:

338

X: —CH2—R1: 7-Cl

339

R3: HCrystalline form: Colorless amorphousNMR analysis: 31)Form: HydrochlorideExample 62Structure:

340

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousNMR analysis: 32)Form: FreeExample 63Structure:

341

X: —CH2—R1: 7-Cl

342

R3: HCrystalline form: Colorless amorphousNMR analysis: 33)Form: FreeExample 64Structure:

343

X: —CH2—R1: 7-Cl

344

R3: HCrystalline form: Colorless amorphousNMR analysis: 34)Form: FreeExample 65Structure:

345

X: —CH2—R1: 7-Cl

346

R3: HCrystalline form: Colorless amorphousNMR analysis: 35)Form: HydrochlorideExample 66Structure:

347

X: —CH2—R1: 7-Cl

348

R3: HCrystalline form: Colorless amorphousNMR analysis: 36)Form: HydrochlorideExample 67Structure:

349

X: —CH2—R1: 7-Cl

350

R3: HCrystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 174-176° C.Form: FreeExample 68Structure:

351

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: White powderSolvent for recrystallization: Ethanol/diethyl etherM.p. 203-204° C.Form: FreeExample 69Structure:

352

X: —CH2—R1: 7-ClR2: —OHR3: HCrystalline form: Colorless amorphousNMR analysis: 37)Form: FreeExample 70Structure:

353

X: —CH2—R1: 7-Cl

354

R3: HCrystalline form: White powderSolvent for recrystallization: Ethyl acetate/n-hexaneM.p. 181-182° C.Form: FreeExample 71Structure:

355

X: —CH2—R1: 7-Cl

356

R3: HCrystalline form: Colorless amorphousNMR analysis: 38)Form: HydrochlorideExample 72Structure:

357

X: —CH2—R1: 7-ClR2: —OCOCH2N(CH3)2R3: HCrystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 153-155° C.Form: HydrochlorideExample 73Structure:

358

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Colorless amorphousNMR analysis: 39)Form: FreeExample 74Structure:

359

X: —CH2—R1: 7-Cl

360

R3: HCrystalline form: White powderSolvent for recrystallization: Acetone/diethyl etherM.p. 153-154.5° C.Form: FreeExample 75Structure:

361

X: —CH2—R1: 7-Cl

362

R3: HCrystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 160-161° C.Form: FreeExample 76Structure:

363

X: —CH2—R1: 7-Cl

364

R3: HCrystalline form: White powderSolvent for recrystallization: Acetone/diethyl etherNMR analysis: 135-136° C.Form: FreeExample 77Structure:

365

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: White powderSolvent for recrystallization: Ethanol/diethyl etherNMR analysis: 134-136.5° C.Form: FreeExample 78Structure:

366

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: White powderSolvent for recrystallization: Ethanol/diethyl etherNMR analysis: 140.5-142° C.Form: FreeExample 79Structure:

367

X: —CH2—R1: 7-Cl

368

R3: HCrystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneNMR analysis: 199.5-202° C.Form: FreeExample 80Structure:

369

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Colorless amorphousNMR analysis: 40)Form: FreeExample 81Structure:

370

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: White powderSolvent for recrystallization: Dichloromethane/methanol/diethyl etherM.p. 187-190° C.Form: FreeExample 82Structure:

371

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: White powderSolvent for recrystallization: Dichloromethane/methanol/diethyl etherM.p. 189-192° C.Form: FreeExample 83Structure:

372

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: White powderM.p. 205-207° C.Form: FreeExample 84Structure:

373

X: —CH2—R1: 7-Cl

374

R3: HCrystalline form: Colorless amorphousNMR analysis: 41)Form: FreeExample 45Structure:

375

X: —CH2—R1: 7-Cl

376

R3: HCrystalline form: Colorless amorphousNMR analysis: 42)Form: FreeExample 86Structure:

377

X: —CH2—R1: 7-ClR2: —CH2CO2C2H5R3: HCrystalline form: Colorless oilNMR analysis: 43)Form: FreeExample 87Structure:

378

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless oilNMR analysis: 44)Form: FreeExample 88Structure:

379

X: —CH2—R1: 7-Cl

380

R3: HCrystalline form: Colorless oilNMR analysis: 45)Form: FreeExample 89Structure:

381

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless oilNMR analysis: 46)Form: FreeExample 90Structure:

382

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousNMR analysis: 47)Form: FreeExample 91Structure:

383

X: —CH2—R1: 7-Cl

384

R3: HCrystalline form: White powderSolvent for recrystallization: Dichloromethane/diethyl etherM.p. 84-88° C.Form: FreeExample 92Structure:

385

X: —CH2—R1: 7-Cl

386

R3: HCrystalline form: Colorless amorphousNMR analysis: 48)Form: FreeExample 93Structure:

387

X: —CH2—R1: 7-Cl

388

R3: HCrystalline form: Colorless amorphousNMR analysis: 49)Form: FreeExample 94Structure:

389

X: —CH2—R1: 7-Cl

390

R3: HCrystalline form: Colorless amorphousNMR analysis: 50)Form: FreeExample 95Structure:

391

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: White powderSolvent for recrystallization: Ethyl acetate/diethyl ether/n-hexaneM.p. 120-122° C.Form: FreeExample 96Structure:

392

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousNMR analysis: 51)Form: FreeExample 97Structure:

393

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless oilNMR analysis: 52)Form: FreeExample 98Structure:

394

X: —CH2—R1: 7-Cl

395

R3: HCrystalline form: Colorless oilNMR analysis: 53)Form: FreeExample 99Structure:

396

X: —CH2—R1: 7-ClR2: —CH2CO2C2H5R3: HCrystalline form: Colorless oilNMR analysis: 54)Form: FreeExample 100Structure:

397

X: —CH2—R1: 7-ClR2: —CH2CO2C2H5R3: HCrystalline form: Colorless amorphousNMR analysis: 55)Form: FreeExample 101Structure:

398

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousNMR analysis: 56)Form: FreeExample 102Structure:

399

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousNMR analysis: 57)Form: FreeExample 103Structure:

400

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousNMR analysis: 58)Form: FreeExample 104Structure:

401

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousNMR analysis: 59)Form: FreeExample 105Structure:

402

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousNMR analysis: 60)Form: FreeExample 106Structure:

403

X: —CH2—R1: 7-ClR2 and R3: ═OCrystalline form: White powderRecrystallization solvent: Acetone/n-hexaneNMR analysis: 61)Form: FreeExample 107Structure:

404

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousNMR analysis: 62)Form: FreeExample 108Structure:

405

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousNMR analysis: 63)Form: FreeExample 109Structure:

406

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 169-171° C.Form: FreeExample 110Structure:

407

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousNMR analysis: 64)Form: FreeExample 111Structure:

408

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Colorless amorphousNMR analysis: 65)Form: FreeExample 112Structure:

409

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 139.5-142° C.Form: FreeExample 113Structure:

410

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousNMR analysis: 66)Form: FreeExample 114Structure:

411

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 226° C.Form: FreeExample 115Structure:

412

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Acetone/diethyl etherM.p. 142-142.5° C.Form: FreeExample 116Structure:

413

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousNMR analysis: 67)Form: FreeExample 117Structure:

414

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: White powderSolvent for recrystallization: Ethanol/diethyl etherNMR analysis: 235-237° C. (decomposed)Form: FreeExample 118Structure:

415

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: White powderSolvent for recrystallization: Ethanol/diethyl etherNMR analysis: 183° C.Form: FreeExample 119Structure:

416

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneNMR analysis: 68)Form: FreeExample 120Structure:

417

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 192° C.Form: FreeExample 121Structure:

418

X: —CH2—R1: 7-Cl

419

R3: HCrystalline form: Colorless amorphousNMR analysis: 69)Form: FreeExample 122Structure:

420

X: —CH2—R1: 7-Cl

421

R3: HCrystalline form: Colorless amorphousNMR analysis: 70)Form: FreeExample 123Structure:

422

X: —CH2—R1: 7-Cl

423

R3: HCrystalline form: Colorless amorphousNMR analysis: 71)Form: HydrochlorideExample 124Structure:

424

X: —CH2—R1: 7-Cl

425

R3: HCrystalline form: Yellow powderSolvent for recrystallization: EthanolM.p. 182-184° C.Form: HydrochlorideExample 125Structure:

426

X: —CH2—R1: 7-Cl

427

R3: HCrystalline form: Colorless amorphousNMR analysis: 72)Form: HydrochlorideExample 126Structure:

428

X: —CH2—R1: 7-Cl

429

R3: HCrystalline form: Colorless amorphousNMR analysis: 73)Form: HydrochlorideExample 127Structure:

430

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Yellow powderSolvent for recrystallization: Ethanol/diethyl etherM.p. 168° C.Form: FreeExample 128Structure:

431

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: White powderSolvent for recrystallization: Dichloromethane/diethyl etherM.p. 186-188° C.Form: FreeExample 129Structure:

432

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: White powderSolvent for recrystallization: Ethanol/diethyl etherM.p. 120° C.Form: FreeExample 130Structure:

433

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousNMR analysis: 74)Form: FreeExample 131Structure:

434

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: White needlesSolvent for recrystallization: Ethanol/diethyl etherM.p. 109-111° C.Form: FreeExample 132Structure:

435

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousNMR analysis: 75)Form: FreeExample 133Structure:

436

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Yellow needlesSolvent for recrystallization: Methanol/diethyl etherM.p. 202-203° C.Form: FreeExample 134Structure:

437

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: White needlesSolvent for recrystallization: Acetone/n-hexaneM.p. 235° C.Form: FreeExample 135Structure:

438

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: White powderSolvent for recrystallization: Ethanol/diethyl etherM.p. 176° C.Form: FreeExample 136Structure:

439

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousNMR analysis: 76)Form: FreeExample 137Structure:

440

X: —CH2—R1: 7-Cl

441

R3: HCrystalline form: Colorless amorphousNMR analysis: 77)Form: FreeExample 138Structure:

442

X: —CH2—R1: 7-Cl

443

R3: HCrystalline form: White powderNMR analysis: 78)Form: Free

[0680] NMR analysis:

[0681] 1) (Example 9) 1H-NMR (200 MHz, CDCl3) δ ppm: 0.78-5.25 (23H, m), 2.96 and 3.20 (all 3H, s), 3.71 (3H, s), 3.83 (3H, s), 6.51-7.18 (6H, m)

[0682] 2) (Example 10) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.20-2.25 (14H, m), 2.30-2.55 (1H, m), 2.60-3.30 (3H, m), 3.50-3.90 (1H, m), 4.45-4.60 and 5.10-5.30 (1H, m), 6.15 (1H, brs), 6.59 (1H, d, J=8.3 Hz), 6.85-7.00 (3H, m), 7.10-7.35 (3H, m)

[0683] 3) (Example 11) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.20-3.40 (22H, m), 2.21 and 2.34 (3H, s), 3.50-3.90 (5H, m), 4.40-4.60 and 5.05-5.20 (1H, m), 6.50-6.60 (1H, m), 6.85-6.95 (1H, m), 7.00-7.15 (3H, m), 7.25-7.50 (2H, m)

[0684] 4) (Example 12) 1H-NMR (200 MHz, CDCl3) δ ppm: 0.82, 1.02 and 1.08 (all 6H, each t, J=7 Hz), 1.2-4.0, 4.35-4.65 and 4.95-5.24 (all 27H, m), 6.35-6.70 (1H, m), 6.75-7.65 (10H, m)

[0685] 5) (Example 15) 1H-NMR (200 MHz, CDCl3) δ ppm: 0.71-2.24 (11H, m), 2.25-5.17 (21H, m), 5.71-7.54 (9H, m)

[0686] 6) (Example 16) 1H-NMR (200 MHz, CDCl3) δ ppm: 0.78-5.16 (32H, m), 5.79-7.51 (10H, m)

[0687] 7) (Example 21) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.00-5.26 (17H, m), 2.28 and 2.34 (each 3H, each s), 6.54-6.75 (1H, m), 6.89-7.93 (8H, m), 8.48-8.74 (1H, m)

[0688] 8) (Example 22) 1H-NMR (200 MHz, CDCl3) δ ppm: 0.85, 1.00 and 1.07 (all 6H, each t, J=7 Hz), 1.1-4.0, 4.35-4.65, 4.65-4.95 and 4.95-5.25 (all 27H, m), 6.4-6.65 (1H, m), 6.75-7.65 (10H, m)

[0689] 9) (Example 23) 1H-NMR (200 MHz, CDCl3) δ ppm: 2.15 (3H, s), 2.40 (3H, s), 2.71-4.00 (7H, m), 4.01-4.39 (1H, m), 4.69-5.01 (1H, m), 6.42-7.55 (10H, m)

[0690] 10) (Example 25) 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.03-2.08 (4H, m), 1.22 (6H, t, J=7.1 Hz), 2.62-4.95 (22H, m), 6.23-7.42 (6H, m), 10.45-11.47 (1H, m)

[0691] 11) (Example 26) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.34-1.72 (1H, m), 1.81-2.25 (3H, m), 2.57-3.18 (3H, m), 3.70 (3H, s), 3.82 (3H, s), 4.35-5.22 (1H, m), 6.53-6.69 (2H, m), 6.73 (1H, dd, J=8.4 Hz, 1.8 Hz), 6.82 (1H, d, J=1.8 Hz), 6.91 (1H, dd, J=8.4 Hz, 2.4 Hz), 7.24 (1H, d, J=2.4 Hz)

[0692] 12) (Example 27) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.32-2.14 (4H, m), 2.57-3.20 (3H, m), 3.52 (3H, s), 3.73 (3H, s), 4.82-5.05 (1H, m), 6.16 (1H, d, J=2.2 Hz), 6.35 (1H, dd, J=8.4 Hz, 2.2 Hz), 6.64 (1H, d, J=8.2 Hz), 6.81 (1H, dd, J=8.4 Hz, 2.4 Hz), 7.06-7.24 (2H, m)

[0693] 13) (Example 28) 1H-NMR (200 MHz, DMSO-d6) δ ppm: 0.78-2.13 (13H, m), 2.65-5.12 (13H, m), 3.17 and 3.33 (all 3H, s), 3.95 (2H, q, J=6.8 Hz), 6.55-7.58 (7H, m), 10.53-11.48 (1H, m)

[0694] 14) (Example 29) 1H-NMR (200 MHz, DMSO-d6) δ ppm: 0.98-2.06 (13H, m), 2.61-4.88 (21H, m), 6.18-7.45 (6H, m), 10.42-11.52 (1H, m)

[0695] 15) (Example 30) 1H-NMR (200 MHz, DMSO-d6) δ ppm: 0.92-1.95 (7H, m), 2.34-4.43 (14H, m), 2.41 and 2.53 (all 3H, s), 2.77 (6H, s), 6.52-7.38 (6H, m), 10.58-11.57 (2H, m)

[0696] 16) (Example 31) 1H-NMR (200 MHz, DMSO-d6) δ ppm: 0.96-2.03 (4H, m), 2.33-4.62 (13H, m), 2.41 and 2.53 (all 3H, s), 2.76 (3H, s), 3.34 (3H, s), 6.52-7.48 (6H, m), 11.48 (1H, brs)

[0697] 17) (Example 32) 1H-NMR (200 MHz, DMSO-d6) δ ppm: 0.96-4.87 (22H, m), 2.40 and 2.53 (all 3H, s), 2.73 and 2.77 (all 3H, s), 6.51-7.45 (6H, m), 11.36 (1H, brs)

[0698] 18) (Example 34) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.17-5.24 (22H, m), 6.41-7.58 (12H, m)

[0699] 19) (Example 35) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.10-5.24 (26H, m), 6.32-7.69 (11H, m)

[0700] 20) (Example 36) 1H-NMR (200 MHz, CDCl3) δ ppm: 0.74-5.24 (32H, m), 6.28-7.70 (11H, m)

[0701] 21) (Example 38)

[0702]

1
H-NMR (200 MHz, CDCl3) δ ppm: 1.1-4.0, 4.35-4.65, 4.65-5.0 and 5.0-5.25 (all 27H, m), 6.4-6.65 (1H, m), 6.75-7.6 (10H, m)

[0703] 22) (Example 39) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.1-4.0, 4.35-4.7 and 4.95-5.25 (all 28H, m), 5.7-6.0 (1H, m), 6.4-6.65 (1H, m), 6.75-7.6 (10H, m)

[0704] 23) (Example 40) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.2-4.65 and 4.95-5.25 (all 25H, m), 6.35-6.65 and 6.65-8.2 (all 11H, m)

[0705] 24) (Example 46) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.2-3.95, 4.45-4.65, 4.7-4.9 and 5.0-5.25 (all 27H, m), 6.4-6.65 and 6.75-7.6 (all 11H, m)

[0706] 25) (Example 47) 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.12-2.06 (20H, m), 2.66-4.40 (21H, m), 3.18 and 3.33 (all 3H, s), 6.53-7.41 (7H, m), 10.67-11.53 (2H, m)

[0707] 26) (Example 48) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.1-3.95, 4.45-4.65 and 4.95-5.25 (all 29H, m), 5.7-6.05 (1H, m), 6.35-6.65 (1H, m), 6.75-7.65 (9H, m)

[0708] 27) (Example 49) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.22-2.34 (4H, m), 2.42-3.42 (3H, m), 2.82 (3H, s), 3.01 (3H, s), 3.68 (3H, s), 4.81-5.41 (1H, m), 5.08 (2H, s), 6.42-7.12 (5H, m), 7.13-7.72 (5H, m)

[0709] 28) (Example 50) 1H-NMR (200 MHz, DMSO-d6) δ ppm: 0.90-2.25 (4H, m), 1.17 (6H, t, J=7.10 Hz), 2.40-3.90 (17H, m), 4.63-5.17 (1H, m), 4.98 (2H, s), 6.52-7.21 (5H, m), 7.24-7.65 (5H, m), 10.16-10.70 (1H, m)

[0710] 29) (Example 59) 1H-NMR (200 MHz, CDCl3) δ ppm: 0.8-1.2 (6H, m), 1.2-4.0, 4.4-4.65 and 5.0-5.25 (20H, m), 6.45-6.65 (1H, m), 6.6-7.75 (12H, m)

[0711] 30) (Example 60) 1H-NMR (200 MHz, CDCl3) δ ppm: 0.8-1.15 (6H, m), 1.15-3.95, 4.35-4.65 and 4.95-5.25 (all 20H, m, 2.96, 3.17 (each s)), 6.4-7.6 (13H, m)

[0712] 31) (Example 61) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.06-2.41 (7H, m), 2.31 (3H, s), 2.51-4.38 (16H, m), 4.51-4.92 (2H, m), 6.53-7.52 (10H, m), 12.52-12.94 (1H, m)

[0713] 32) (Example 62) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.13-2.26 (5H, m), 2.02 (3H, s), 2.58-5.29 (7H, m), 3.69 (3H, s), 6.49-7.45 (10H, m)

[0714] 33) (Example 63) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.15-5.29 (17H, m), 2.16 (3H, s), 2.34 (3H, s), 6.47-7.62 (11H, m)

[0715] 34) (Example 64) 1H-NMR (200 MHz, CDCl3) δ ppm: 0.70-1.19 (6H, m), 1.20-5.25 (20H, m), 2.16 (3H, m), 6.48-7.62 (11H, m)

[0716] 35) (Example 65) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.02-5.28 (23H, m), 2.02 (3H, s), 6.52-7.50 (10H, m), 11.68-12.41 (1H, m)

[0717] 36) (Example 66) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.04-5.32 (29H, m), 2.02 (3H, s), 6.48-7.51 (10H, m), 11.87-12.28 (1H, m)

[0718] 37) (Example 69) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.46-2.41 (4H, m), 2.14 (3H, s), 2.68-2.98 (1H, m), 3.27-3.83 (4H, m), 4.68-5.27 (2H, m), 6.47-7.54 (9H, m), 7.60 (1H, d, J=2.16 Hz)

[0719] 38) (Example 71) 1H-NMR (200 MHz, CDCl3) δ ppm: 0.86-5.20 (32H, m), 6.51-7.52 (10H, m), 11.62-12.24 (1H, m)

[0720] 39) (Example 73) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.28-2.28 (4H, m), 2.14 (3H, s), 2.58-2.92 (2H, m), 2.93-3.28 (1H, m), 3.58 (3H, s), 4.82-5.12 (1H, m), 6.56 (1H, s), 6.65-6.96 (3H, m), 6.97-7.48 (6H, m)

[0721] 40) (Example 80) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.21-2.25 (4H, m), 2.01 (3H, s), 2.26-3.20 (3H, m), 3.59 (3H, s), 4.86-5.22 (1H, m), 6.42-7.45 (10H, m)

[0722] 41) (Example 84) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.1-4.0, 4.35-4.65 and 5.0-5.25 (all 20H, m, 2.34 (s)), 6.45-6.7 (1H, m), 6.91 (1H, dd, J=2 Hz, 8 Hz), 7.05 (1H, d, J=2 Hz), 7.15-7.7 (9H, m)

[0723] 42) (Example 85) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.2-3.95, 4.35-4.65, 5.0-5.25 (all 20H, m, 2.33 (s)), 6.4-7.55 [12H, m, 6.59 (d, J=8 Hz), 6.79 (d, J=8.5 Hz)]

[0724] 43) (Example 86) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.1-2.2 (7H, m), 2.45-3.3, 3.35-3.9, 4.0-4.35, 4.35-4.65 and 4.95-5.35 (all 9H, m, 5.09 (s)), 6.45-6.65 (1H, m), 6.77 (2H, d, J=8.5 Hz), 6.92 (1H, dd, J=2 Hz, 8.5 Hz), 7.05-7.6 (7H, m)

[0725] 44) (Example 87) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.15-2.2 (4H, m), 2.5-3.3, 3.35-3.9, 4.3-4.6 and 4.9-5.3 (all 7H, m, 5.06 (s)), 4.45-6.65 (1H, m), 6.74 (2H, d, J=8.5 Hz), 6.93 (1H, dd, J=2 Hz, 8.5 Hz), 7.12 (1H, d, J=2 Hz), 7.12-7.55 (6H, m)

[0726] 45) (Example 88) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.15-2.85, 2.85-4.0, 4.35-4.65 and 4.9-5.35 (all 22H, 2.33, 5.10 (each s)), 6.4-6.65 (1H, m), 6.80 (2H, d, J=8.5 Hz), 6.92 (1H, dd, J=2 Hz, 8.5 Hz), 7.04 (1H, d, J=2 Hz), 7.04-7.6 (6H, m)

[0727] 46) (Example 89) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.20-2.45 (7H, m, 2.27 (s)), 2.5-3.1, 3.1-3.4, 3.4-3.9, 4.35-4.65 and 5.02-5.30 (all 8H, m, 3.72 (s)),6.56 (1H, d, J=8.3 Hz), 6.92 (1H, dd, J=2.3 Hz, 8.4 Hz), 7.10 (1H, d, J=2.2 Hz), 7.10-7.71 (8H, m)

[0728] 47) (Example 90) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.23-2.47 (4H, m), 2.26 (3H, s), 2.6-3.05 (2H, m), 3.10-3.43, 3.48-3.90, 4.35-4.62 and 5.05-5.29 (all 3H, m), 6.56 (1H, d, J=8.3 Hz), 6.90 (1H, dd, J=2.2 Hz, 8.3 Hz), 7.08 (1H, d, J=2.2 Hz), 7.12-7.55 (6H, m), 7.61 (2H, d, J=8.5 Hz)

[0729] 48) (Example 92) 1H-NMR (200 MHz, CDCl3) δ ppm: 0.84, 1.05 and 1.08 (all 6H, each t, J=7 Hz), 1.2-4.0, 4.1-4.7 and 4.8-5.3 (all 25H, m, 2.24 (s)), 2.61 (q, J=7 Hz), 2.99, 3.19 (each s)), 6.4-7.7 (11H, m, 6.55 (d, J=8 Hz))

[0730] 49) (Example 93) 1H-NMR (200 MHz, CDCl3) δ ppm: 0.90, 0.97 and 1.07 (all 6H, each t, J=7 Hz), 1.15-4.02, 4.38-4.65 and 4.95-5.25 (all 23H, m, 2.26, 3.18 (each s)), 6.54 (1H, d, J=8.3 Hz), 6.77-7.70 (10H, m)

[0731] 50) (Example 94) 1H-NMR (200 MHz, CDCl3) δ ppm: 0.82, 1.00 and 1.07 (all 6H, each t, J=7 Hz), 1.15-3.98, 4.47-4.68, 4.95-5.22 and 5.76-6.10 (all 25H, m), 6.40-6.68 and 6.73-7.68 (all 11H, m)

[0732] 51) (Example 96)

[0733]

1
H-NMR (200 MHz, CDCl3) δ ppm: 1.2-2.4 (4H, m), 2.20 (3H, s), 2.5-3.35, 3.4-3.9, 4.25-4.6 and 4.9-6.2 (all 8H, m, 4.22 (s)), 6.4-6.65 (1H, m), 6.75-6.95 (1H, m), 6.95-7.35 (5H, m), 7.42 (2H, d, J=8.5 Hz), 7.81 (2H, d, J=8.5 Hz)

[0734] 52) (Example 97) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.2-2.3, 2.5-3.4, 3.5-4.3, 4.35-4.7 and 5.05-5.35 (all 12H, 3.75 (s)), 6.4-6.7 (1H, m), 6.93 (1H, dd, J=2 Hz, 8.5 Hz), 7.13 (1H, d, J=2 Hz), 7.2-7.8 (9H, m)

[0735] 53) (Example 98) 1H-NMR (200 MHz, CDCl3) δ ppm: 0.85,1.03 and 1.08 (all 6H, each t, J=7 Hz), 1.2-4.0, 4.3-4.65 and 4.9-5.3 (all 22H, 2.99, 3.19, 5.10 (each s)), 6.45-7.6 (11H, m)

[0736] 54) (Example 99) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.27 (3H, t, J=7.1 Hz), 1.20-2.20 (14H, m), 2.30-2.50 (1H, m), 2.60-3.05 (3H, m), 3.10-3.35 (1H, m), 4.10-4.40 (2H, m), 4.45-4.65 (1H, m), 6.57 (1H, d, J=8.4 Hz), 6.96 (1H, d, J=8.1 Hz), 7.00 (2H, d, J=8.0 Hz), 7.10-7.35 (3H, m)

[0737] 55) (Example 100) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.08-2.41 (5H, m),1.25 (3H, t, J=7.10 Hz), 2.16 (3H, s), 2.54-5.32 (6H, m), 6.48-7.54 (11H, m)

[0738] 56) (Example 101) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.14-2.36 (5H, m), 2.26 (3H, s), 2.51-5.35 (4H, m), 6.45-7.50 (11H, m), 8.65-13.90 (1H, m)

[0739] 57) (Example 102)

[0740]

1
H-NMR (200 MHz, CDCl3) δ ppm: 1.18-2.39 (5H, m), 2.57-3.05 (2H, m), 3.09-5.28 (2H, m), 3.67, 3.72 and 3.82 (each 3H, each s), 6.48-7.81 (10H, m)

[0741] 58) (Example 103) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.14-2.26 (4H, m), 2.01 (3H, s), 2.52-3.10 (2H, m), 3.01-5.28 (3H, m), 3.61 (3H, s), 6.48-7.88 (10H, m), 8.50-13.9 (1H, m)

[0742] 59) (Example 104) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.18-2.32 (4H, m), 2.57-3.09 (2H, m), 3.10-5.29 (3H, m), 3.66 and 3.81 (each 3H, each s), 6.45-7.80 (10H, m), 8.03-13.80 (1H, m)

[0743] 60) (Example 105) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.13-2.37 (4H, m), 2.14 (3H, s), 2.54-2.97 (2H, m), 2.98-5.20 (3H, m), 3.68 and 3.74 (each 3H, each s), 6.50-7.52 (10H, m)

[0744] 61) (Example 106) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.41-4.06 (5H, m), 2.13 (3H, s), 3.39 (3H, s), 4.36-5.41 (1H, m), 6.49 (1H, s), 6.79 (1H, d, J=8.44 Hz), 6.88 (1H, d, J=7.42 Hz), 7.01-7.62 (6H, m), 7.79 (1H, d, J=2.24 Hz)

[0745] 62) (Example 107) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.10-2.21 (5H, m), 2.51-3.26 (3H, m), 3.27-4.11 (4H, m), 3.77 (3H, s), 4.36-4.88 (4H, m), 5.71-7.58 (10H, m)

[0746] 63) (Example 108) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.06-2.21 (4H, m), 2.49-5.23 (11H, m), 3.73 (3H, s), 5.78-7.50 (9H, m)

[0747] 64) (Example 110) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.04-2.26 (4H, m), 2.47-5.20 (14H, m), 5.58-7.72 (10H, m)

[0748] 65) (Example 111) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.31-1.69 (1H, m), 1.70-2.24 (3H, m), 2.55-3.20 (3H, m), 4.88-5.20 (1H, m), 5.03 (2H, s), 6.51-7.51 (16H, m)

[0749] 66) (Example 113) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.15-2.40 (4H, m), 2.28 (3H, s), 2.60-5.29 (5H, m), 3.74 (3H, s), 6.54-6.78 (1H, m), 6.88-7.06 (1H, m), 7.09-7.46 (6H, m), 7.58-7.79 (1H, m), 8.46-8.66 (1H, m)

[0750] 67) (Example 116) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.10-2.30 (4H, m), 2.49-5.29 (5H, m), 3.70 (3H, s), 3.87 (2H, s), 6.41-7.75 (12H, m)

[0751] 68) (Example 119) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.21-2.31 (4H, m), 2.60-5.27 (5H, m), 3.75 (3H, s), 6.41-6.63 (1H, m), 6.80-7.53 (2H, m), 7.48 (2H, d, J=8.24 Hz), 7.74 (2H, d, J=8.42 Hz), 9.99-10.02 (1H, m)

[0752] 69) (Example 121) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.16-5.23 (17H, m), 2.35 (3H, s), 6.41-6.62 (1H, m), 6.78-7.53 (2H, m), 7.61 (2H, d, J=8.3 Hz), 7.73 (2H, d, J=8.3 Hz), 9.94 (1H, s)

[0753] 70) (Example 122) 1H-NMR (200 MHz, CDCl3) δ ppm: 0.90-5.24 (26H, m), 6.40-6.61 (1H, m), 6.74-7.82 (6H, m), 9.88-10.01 (1H, m)

[0754] 71) (Example 123) 1H-NMR (200 MHz, CDCl3) δ ppm: 0.94 (3H, t, J=7.3 Hz), 0.78-5.25 (26H, m), 6.48-7.82 (11H, m), 12.35-13.74 (1H, m)

[0755] 72) (Example 125)

[0756]

1
H-NMR (200 MHz, CDCl3) δ ppm: 0.85-5.23 (28H, m), 6.37-7.80 (10H, m), 12.29-13.40 (1H, m)

[0757] 73) (Example 126) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.02-5.22 (27H, m), 6.37-7.76 (11H, m), 12.54-13.50 (1H, m)

[0758] 74) (Example 130)

[0759]

1
H-NMR (200 MHz, CDCl3) δ ppm: 1.08-2.37 (4H, m), 2.51-5.45 (11H, m), 3.83 (3H, s), 6.34-7.62 (10H, m)

[0760] 75) (Example 132) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.11-2.32 (4H, m), 2.12 (3H, s), 2.41-5.30 (7H, m), 6.38-8.08 (11H, m), 8.91-13.00 (1H, m)

[0761] 76) (Example 136) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.03-2.36 (4H, m), 2.13 (3H, s), 2.38-5.28 (7H, m), 3.71 (3H, s), 6.41-8.09 (11H, m)

[0762] 77) (Example 137) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.05-5.10 (25H, m), 6.05-7.50 (15H, m)

[0763] 78) (Example 138) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.03-5.08 (20H, m), 2.34 (3H, s), 6.58-7.53 (6H, m), 8.39-9.04 (1H, m)

[0764] 79) (Example 24) 1H-NMR (200 MHz, CDCl3) δ ppm: 0.78-5.25 (23H, m), 2.96 and 3.20 (all 3H, s), 3.71 (3H, s), 3.83 (3H, s), 6.51-7.18 (6H, m)

[0765] 80) (Example 52) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.12-2.36 (4H, m), 2.20 (3H, s), 2.56-4.00 (4H, m), 4.25-5.41 (1H, m), 6.27-7.76 (11H, m), 10.73-11.74 (1H, m)

[0766] 81) (Example 54) 1H-NMR (200 MHz, CDCl3) δ ppm: 1.3-1.7 (1H, m), 1.7-2.2 (3H, m), 2.55-3.2 (3H, m), 4.85-5.2 (1H, m), 6.3-7.7 (14H, m)

[0767] 82) (Example 55) 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.07-2.04 (10H, m), 2.58-3.98 (18H, m), 4.13-4.36 (1H, m), 4.73 (2H, s), 6.61-7.43 (10H, m), 7.87-8.01 (1H, m), 9.21 (1H, s), 10.32 (1H, brs)

[0768] 83) (Example 56) 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.05-2.06 (10H, m), 2.43-3.80 (15H, m), 4.17-4.40 (1H, m), 4.73 (2H, m), 6.63-7.48 (10H, m), 7.84-7.98 (1H, m), 8.56-8.71 (1H, m), 9.22 (1H, s), 10.34 (1H, brs)

[0769] 84) (Example 57) 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.08-2.02 (10H, m), 2.62-3.99 (18H, m), 4.12-4.39 (1H, m), 4.82 (2H, s), 6.61-7.57 (9H, m), 7.96-8.11 (1H, m), 9.33 (1H, s), 10.21 (1H, brs)

[0770] 85) (Example 58) 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.04-2.01 (10H, m), 2.43-3.80 (15H, m), 4.13-4.40(1H, m), 4.82 (2H, s), 6.60-7.53 (9H, m), 7.92-8.08 (1H, m), 8.56-8.71 (1H, m), 9.33 (1H, s), 10.35 (1H, brs)

Example 139

[0771] To a solution of 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-[2-methoxy-4-{N-[2-(2-methylphenoxy)ethyl]-N-trifluoroacetylamino}benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.45 g) in methanol (20 ml) is added a solution of potassium carbonate (0.11 g) in water (5 ml), and the mixture is stirred at room temperature for 12 hours. The mixture is evaporated to remove the solvent, and thereto is added water. The mixture is extracted with ethyl acetate, and the extract is dried, evaporated to remove the solvent. The resulting residue is purified by silica gel column chromatography (solvent; dichloromethane:methanol=80:1→50:1→30:1), and recrystallized from acetone/n-hexane to give 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-{2-methoxy-4-[2-(2-methylphenoxy)ethylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine (0.12 g) as white powder.

[0772] M.p. 160-161° C.

Example 140

[0773] To a solution of 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-(2-methoxy-4-trifluoroacetylaminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (0.4 g) in dry tetrahydrofuran (20 ml) are added triphenyl-phosphine (0.54 g) and o-(2-hydroxyethoxy)toluene (0.29 g) at room temperature. To the mixture is added dropwise a solution of diethyl azodicarboxylate (0.32 ml) in dry tetrahydrofuran (5 ml), and the mixture is stirred at room temperature for 16 hours. To the mixture is added water, and the mixture is extracted with diethyl ether. The ether layer is dried, evaporated to remove the solvent, and the residue is purified by silica gel column chromatography (solvent; dichloromethane:methanol=50:1→30:1) to give 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-[2-methoxy-4-[N-[2-(2-methylphenoxy)ethyl]-N-trifluoroacetylamino]benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.46 g) as colorless amorphous.

[0774]

1
H-NMR (200 MHz, CDCl3) δ ppm: 1.05-5.10 (25H, m), 6.05-7.50 (15H, m)

[0775] The suitable starting compounds are treated in the same manner as in Example 140 to give the compounds of Examples 13-16, 74-78, 108 and 110.

Example 141

[0776] To a solution of 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-(2-methoxy-2-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (2.0 g) in pyridine (30 ml) is added dropwise trifluoroacetic anhydride (1.14 ml) under ice-cooling. To the reaction solution is added a saturated aqueous sodium hydrogen carbonate solution, and the mixture is extracted with ethyl acetate. The extract is washed with water, dried, and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; dichloromethane:methanol=50:1→30:1), and crystallized from acetone/n-hexane to give 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-(2-methoxy-4-trifluoroacetylaminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (1.86 g) as white powder.

[0777]

1
H-NMR (200 MHz, CDCl3) δ ppm: 1.03-5.08 (20H, m), 2.34 (3H, s), 6.58-7.53 (6H, m), 8.39-9.04 (1H, m)

[0778] The suitable starting compounds are treated in the same manner as in Example 141 to give the compounds of Examples 7, 8 and 55-58.

Example 142

[0779] To a solution of 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-(2-methoxy-2-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (0.8 g) in methanol (30 ml) are added o-tolualdehyde (0.35 ml) and acetic acid (1 ml), and the mixture is stirred at 50-60° C. for 2-3 hours. To the mixture is added sodium cyanoborohydride (0.11 g) at room temperature, and the mixture is stirred for two hours. The mixture is evaporated to remove the solvent, and to the residue is added water. The mixture is extracted with ethyl acetate, and the extract is dried, and evaporated. The residue is purified by silica gel column chromatography (solvent; dichloromethane:methanol=50:1→25:1), and recrystallized from acetone/diethyl ether to give 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-[2-methoxy-4-(2-methylbenzylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.71 g) as white powder.

[0780] M.p. 153-154.5° C.

[0781] The suitable starting compounds are treated in the same manner as in Example 142 to give the compounds of Examples 13-16, 75-78, 108, 110 and 137.

Example 143

[0782] To a suspension of 7-chloro-5-methoxycarbonylmethyl-1-(2-methoxy-4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (2.6 g) in ethanol (100 ml) are added sodium carbonate (1.5 g), o-xylene dibromide (1.87 g) and sodium iodide (2.42 g), and the mixture is stirred at 60-70° C. for three hours. The mixture is evaporate to remove the solvent, and to the residue is added water, and the mixture is extracted with ethyl acetate. The extract is dried, and evaporate to remove the solvent. The residue is purified by silica gel column chromatography (solvent; ethyl acetate:n-hexane=1:10→1:5) to give 7-chloro-5-methoxycarbonylmethyl-1-[2-methoxy-4-(2-isoindolinyl)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.32 g) as colorless amorphous.

[0783]

1
H-NMR (200 MHz, CDCl3) δ ppm: 1.10-2.21 (5H, m), 2.51-3.26 (3H, m), 3.27-4.11 (4H, m), 3.77 (3H, s), 4.36-4.88 (4H, m), 5.71-7.58 (10H, m)

[0784] The suitable starting compounds are treated in the same manner as in Example 143 to give the compounds of Examples 79 and 101.

Example 144

[0785] To a solution of 7-chloro-1-(3-methoxy-4-hydroxybenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (0.7 g) in dry dimethylformamide (20 ml) are added potassium carbonate (0.35 g) and 2-chlorobenzyl chloride (0.32 ml), and the mixture is stirred at room temperature overnight. To the reaction solution is added water, and the mixture is extracted with ethyl acetate. The extract is washed with water, dried, and evaporated to remove the solvent. The residue is recrystallized from acetone/diethyl ether to give 7-chloro-1-[3-methoxy-4-(2-chlorobenzyloxy)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.76 g) as white powder.

[0786] M.p. 135° C.

[0787] The suitable starting compounds are treated in the same manner as in Example 144 to give the compounds of Examples 24-33, 41, 43-45, 47, 49-51, 86-88 and 98.

Example 145

[0788] To a solution of 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-(4-formylbenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (0.29 g) in methanol (30 ml) are added o-toluizine (0.2 ml) and acetic acid until the mixture becomes pH 4. The mixture is heated with stirring at 50° C. for 8 hours, and thereto is added sodium cyanoborohydride (0.085 g) with ice-cooling, and the mixture is stirred for one hour. The mixture is evaporated to remove the methanol, and thereto is added water. The mixture is extracted with ethyl acetate, and the extract is washed with water, dried, and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; dichloromethane:methanol=100:1→50:1) to give 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-[4-(2-methylanilinomethyl)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.1 g) as colorless amorphous.

[0789]

1
H-NMR (200 MHz, CDCl3) δ ppm: 1.10-5.24 (26H, m), 6.32-7.69 (11H, m)

[0790] The suitable starting compounds are treated in the same manner as in Example 145 to give the compound of Example 36.

Example 146

[0791] To a solution of 7-chloro-1-(3-methoxy-4-aminobenzoyl)-2,3,4,5-tetrahydro -1H-benzazepine (0.7 g) in pyridine (5 ml) is added N,N-dimethylcarbamic chloride (0.42 ml), and the mixture is stirred at 60-70° C. for two hours. The mixture is made acidic with hydrochloric acid, and then extracted with ethyl acetate. The mixture is washed with a saturated aqueous sodium hydrogen carbonate solution, and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; ethyl acetate:n-hexane=1:10→1:1→3:1), and recrystallized from ethanol/diethyl ether to give 7-chloro-1-(3-methoxy-4-dimethylaminocarbonylaminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (0.33 g) as white plates.

[0792] M.p. 230-232° C.

[0793] The suitable starting compounds are treated in the same manner as in Examples 1 and 2 to give the following compounds.

444

Example 147Structure:

445

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Colorless amorphousForm: FreeExample 148Structure:

446

X: —CH2—R1: 7-Cl

447

R3: HCrystalline form: Colorless amorphousForm: FreeExample 149Structure:

448

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderM.p. 194-195° C.Form: FreeExample 150Structure:

449

X: —CH2—R1: 7-Cl

450

R3: HCrystalline form: Colorless amorphousForm: FreeExample 151Structure:

451

x: —CH2—R1: 7-Cl

452

R3: HCrystalline form: Colorless amorphousForm: FreeExample 152Structure:

453

X: —CH2—R1: 7-Cl

454

R3: HCrystalline form: Colorless amorphousForm: FreeExample 153Structure:

455

X: —CH2—R1: 7-Cl

456

R3: HCrystalline form: Colorless amorphousForm: FreeExample 154Structure:

457

X: —CH2—R1: 7-Cl

458

R3: HCrystalline form: Colorless amorphousForm: FreeExample 155Structure:

459

X: —CH2—R1: 7-Cl

460

R3: HCrystalline form: Colorless amorphousForm: FreeExample 156Structure:

461

X: —CH2—R1: 7-Cl

462

R3: HCrystalline form: Colorless amorphousForm: FreeExample 157Structure:

463

X: —CH2—R1: 7-Cl

464

R3: HCrystalline form: Colorless amorphousForm: FreeExample 158Structure:

465

X: —CH2—R1: 7-Cl

466

R3: HCrystalline form: Colorless amorphousForm: FreeExample 159Structure:

467

X: —CH2—R1: 7-Cl

468

R3: HCrystalline form: Colorless amorphousForm: FreeExample 160Structure:

469

X: —CH2—R1: 7-ClR2: —CH2CONH(CH2)2N(C2H5)2R3: HCrystalline form: Colorless amorphousForm: FreeExample 161Structure:

470

X: —CH2—R1: 7-Cl

471

R3: HCrystalline form: Colorless amorphousForm: FreeExample 162Structure:

472

X: —CH2—R1: 7-ClR2: —CH2CONH2R3: HCrystalline form: Brown amorphousForm: FreeExample 163Structure:

473

x: —CH2—R1: HR2: HR3: HCrystalline form: Brown amorphousForm: FreeExample 164Structure:

474

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderM.p. 230-232° C. (decomposed)Form: FreeExample 165Structure:

475

X: —CH2—R1: 7-Cl

476

R3: HCrystalline form: Yellow amorphousForm: FreeExample 166Structure:

477

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderM.p. 243-245° C. (decomposed)Form: FreeExample 167Structure:

478

X: —CH2—R1: HR2: HR3: HCrystalline form: Colorless amorphousForm: FreeExample 168Structure:

479

X: —CH2—R1: HR2: HR3: HCrystalline form: Pale yellow powderM.p. 203-205° C. (decomposed)Form: FreeExample 169Structure:

480

X: —CH2—R1: HR2: HR3: HCrystalline form: Brown powderM.p. 178-180° C.Form: FreeExample 170Structure:

481

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderM.p. 202-204° C. (decomposed)Form: FreeExample 171Structure:

482

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderM.p. 118-120° C.Form: FreeExample 172Structure:

483

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderM.p. 179-181° C. (decomposed)Form: FreeExample 173Structure:

484

X: —CH2—R1: 7-Cl

485

R3: HCrystalline form: Colorless amorphousForm: FreeExample 174Structure:

486

X: —CH2—R1: H

487

R3: HCrystalline form: Colorless amorphousForm: FreeExample 175Structure:

488

X: —CH2—R1: H

489

R3: HCrystalline form: Colorless amorphousForm: FreeExample 176Structure:

490

X: —CH2—R1: 7-ClR2:—CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 177Structure:

491

X: —CH2—R1: 7-ClR2:—CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 178Structure:

492

X: —CH2—R1: 7-ClR2:—CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 179Structure:

493

X: —CH2—R1: 7-ClR2:—CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 180Structure:

494

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 181Structure:

495

X: —CH2—R1: HR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 182Structure:

496

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Pale yellow oilForm: FreeExample 183Structure:

497

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 184Structure:

498

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 185Structure:

499

X: —CH2—R1: HR2: HR3: HCrystalline form: Colorless amorphousForm: FreeExample 186Structure:

500

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 187Structure:

501

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 188Structure:

502

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 189Structure:

503

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 190Structure:

504

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 191Structure:

505

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: White powderM.p. 130-132° C.Form: FreeExample 192Structure:

506

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 193Structure:

507

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 194Structure:

508

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 195Structure:

509

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 196Structure:

510

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 197Structure:

511

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: White powderForm: FreeExample 198Structure:

512

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 199Structure:

513

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: White powderForm: FreeExample 200Structure:

514

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: EthanolM.p. 188-190° C.Form: FreeExample 201Structure:

515

X: —CH2—R1: HR2: HR3: HCrystalline form: Colorless amorphousForm: FreeExample 202Structure:

516

X: —CH2—R1: H

517

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 203Structure:

518

X: —CH2—R1: HR2: HR3: HCrystalline form: Colorless amorphousForm: FreeExample 204 Structure:

519

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: EthanolM.p. 186.5-188° C.Form: FreeExample 205Structure:

520

X: —CH2—R1: H

521

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 206Structure:

522

X: —CH2—R1: H

523

R3: HCrystalline form: Yellow amorphousForm: HydrochlorideExample 207Structure:

524

X: —CH2—R1: H

525

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 208Structure:

526

X: —CH2—R1: 7-Cl

527

R3: HCrystalline form: Colorless amorphousForm: FreeExample 209Structure:

528

X: —CH2—R1: HR2: HR3: HCrystalline form: Colorless amorphousForm: FreeExample 210Structure:

529

X: —CH2—R1: HR2: HR3: HCrystalline form: Colorless amorphousForm: FreeExample 211Structure:

530

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderForm: FreeExample 212Structure:

531

X: —CH2—R1: HR2: HR3: HCrystalline form: Colorless needlesSolvent for recrystallization: Ethyl acetateM.p. 204-205° C.Form: FreeExample 213Structure:

532

X: —CH2—R1: HR2: HR3: HCrystalline form: Colorless prismsSolvent for recrystallization: Ethyl acetateM.p. 157.5-159° C.Form: FreeExample 214Structure:

533

X: —CH2—R1: 7-Cl

534

R3: HCrystalline form: Colorless amorphousForm: FreeExample 215Structure:

535

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Ethyl acetateM.p. 168.5-169.5° C.Form: FreeExample 216Structure:

536

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Ethyl acetateM.p. 177-178° C.Form: FreeExample 217Structure:

537

X: —CH2—R1: HR2: HR3: HCrystalline form: Yellow powderM.p. 195.5-197° C.Form: FreeExample 218Structure:

538

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: EthanolM.p. 177-178° C.Form: FreeExample 219Structure:

539

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderM.p. 234-234.5° C.Form: FreeExample 220Structure:

540

X: —CH2—R1: HR2: HR3: HCrystalline form: Color amorphousForm: FreeExample 221Structure:

541

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderM.p. 143-144.5° C.Form: FreeExample 222Structure:

542

X: —CH2—R1: HR2: HR3: HCrystalline form: Slightly orange powderSolvent for recrystallization: Acetone/diethyl etherM.p. 231.5-233° C.Form: FreeExample 223Structure:

543

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: EthanolM.p. 164-165° C.Form: FreeExample 224Structure:

544

X: —CH2—R1: HR2: HR3: HCrystalline form: Slightly orange powderSolvent for recrystallization: EthanolM.p. 175-176.5° C.Form: FreeExample 225Structure:

545

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: EthanolM.p. 127.5-128.5° C.Form: FreeExample 226Structure:

546

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: EthanolM.p. 176-177° C.Form: FreeExample 227Structure:

547

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: EthanolM.p. 104.5-105.5° C.Form: FreeExample 228Structure:

548

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 229Structure:

549

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: Yellow amorphousForm: FreeExample 230Structure:

550

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderForm: FreeExample 231Structure:

551

X: —CH2—R1: HR2: —CH2CO2HR3: HCrystalline form: Yellow amorphousForm: FreeExample 232Structure:

552

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: Yellow amorphousForm: FreeExample 233Structure:

553

X: —CH2—R1: 7-ClR2: —CH2CO2HR3: HCrystalline form: White powderForm: FreeExample 234Structure:

554

X: —CH2—R1: 7-ClR2: —CH2CO2HR3: HCrystalline form: Colorless amorphousForm: FreeExample 235Structure:

555

X: —CH2—R1: 7-ClR2: —CH2CO2HR3: HCrystalline form: Colorless amorphousForm: FreeExample 236Structure:

556

X: —CH2—R1: HR2: HR3: HCrystalline form: Brown powderM.p. 156-159° C.Form: FreeExample 237Structure:

557

X: —CH2—R1: 7-Cl

558

R3: HCrystalline form: Colorless amorphousForm: FreeExample 238Structure:

559

X: —CH2—R1: 7-Cl

560

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 239Structure:

561

X: —CH2—R1: 7-Cl

562

R3: HCrystalline form: Colorless amorphousForm: FreeExample 240Structure:

563

X: —CH2—R1: 7-Cl

564

R3: HCrystalline form: Colorless amorphousForm: HydrochorideExample 241Structure:

565

X: —CH2—R1: 7-Cl

566

R3: HCrystalline form: Colorless amorphousForm: FreeExample 242Structure:

567

X: —CH2—R1: 7-Cl

568

R3: HCrystalline form: Colorless amorphousFrom: HydrochlorideExample 243Structure:

569

X: —CH2—R1: 7-ClR2: —OCH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 244Structure:

570

X: —CH2—R1: 7-ClR2: —OCH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 245Structure:

571

X: —CH2—R1: 7-Cl

572

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 246Structure:

573

X: —CH2—R1: 7-Cl

574

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 247Structure:

575

X: —CH2—R1: 7-Cl

576

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 248Structure:

577

X: —CH2—R1: 7-Cl

578

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 249Structure:

579

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 84-85.5° C.Form: FreeExample 250Structure:

580

X: —CH2—R1: 7-ClR2: —CH2CONH(CH2)2N(C2H5)2R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 251Structure:

581

X: —CH2—R1: 7-Cl

582

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 252Structure:

583

X: —CH2—R1: 7-Cl

584

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 253Structure:

585

X: —CH2—R1: 7-Cl

586

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 254Structure:

587

X: —CH2—R1: 7-Cl

588

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 255Structure:

589

X: —CH2—R1: 7-ClR2: —CH2CONHC2H5R3: HCrystalline form: Colorless amorphousForm: FreeExample 256Structure:

590

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 181.5-182° C.Form: FreeExample 257Structure:

591

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 181-182° C.Form: FreeExample 258Structure:

592

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Ethanol/diethyl etherM.p. 262-265° C.Form: FreeExample 259Structure:

593

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 159-160° C.Form: FreeExample 260Structure:

594

X: —CH2—R1: 7-ClR2: —CH2CONHC2H5R3: HCrystalline form: Coloreless amorphousForm: FreeExample 261Structure:

595

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powdersolvent for recrystallization: Acetone/n-hexaneM.p. 153° C.Form: FreeExample 262Structure:

596

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Colorless amorphousForm: FreeExample 263Structure:

597

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Colorless amorphousForm: FreeExample 264Structure:

598

X: —CH2—R1: 7-Cl

599

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 265Structure:

600

X: —CH2—R1: 7-ClR2: —CH2CONHCH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 266Structure:

601

X: —CH2—R1: 7-ClR2: —CH2CONH2R3: HCrystalline form: Colorless amorphousForm: FreeExample 267Structure:

602

X: —CH2—R1: 7-Cl

603

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 268Structure:

604

X: —CH2—R1: 7-Cl

605

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 269Structure:

606

X: —CH2—R1: 7-ClR2: —CH2CONH2R3: HCrystalline form: Colorless amorphousForm: FreeExample 270Structure:

607

X: —CH2—R1: 7-Cl

608

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 271Structure:

609

X: —CH2—R1: 7-Cl

610

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 272Structure:

611

X: —CH2—R1: 7-ClR2: —CH2CONHC2H5R3: HCrystalline form: Colorless amorphousForm: FreeExample 273Structure:

612

X: —CH2—R1: 7-Cl

613

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 274Structure:

614

X: —CH2—R1: 7-Cl

615

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 275Structure:

616

X: —CH2—R1: 7-Cl

617

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 276Structure:

618

X: —CH2—R1: 7-Cl

619

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 277Structure:

620

X: —CH2—R1: 7-Cl

621

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 278Structure:

622

X: —CH2—R1: H

623

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 279Structure:

624

X: —CH2—R1: H

625

R3: HCrystalline form: Colorless amorphousForm: FreeExample 280Structure:

626

X: —CH2—R1: H

627

R3: HCrystalline form: White powderSolvent for recrystallization: Ethanol/n-hexaneM.p. 218-221° C.Form: HydrochlorideExample 281Structure:

628

X: —CH2—R1: H

629

R3: HCrystalline form: White powderSolvent for recrystallization: Ethanol/diethyl etherM.p. 214-217° C.Form: HydrochlorideExample 282Structure:

630

X: —CH2—R1: H

631

R3: HCrystalline form: White powderSolvent for recrystallization: Ethanol/diethyl etherM.p. 204-206° C.Form: HydrochlorideExample 283Structure:

632

X: —CH2—R1: 7-ClR2: —CH2CONHCH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 284Structure:

633

X: —CH2—R1: 7-Cl

634

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 285Structure:

635

X: —CH2—R1: 7-Cl

636

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 286Structure:

637

X: —CH2—R1: H

638

R3: HCrystalline form: Colorless amorphousForm: FreeExample 287Structure:

639

X: —CH2—R1: HR2: —CH2CONHC2H5R3: HCrystalline form: Colorless amorphousForm: FreeExample 288Structure:

640

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 289Structure:

641

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 290Structure:

642

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: White powderSolvent for recrystallization: Methanol/diethyl etherM.p. 240-242°C.Form: FreeExample 291Structure:

643

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 292Structure:

644

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 293Structure:

645

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 294Structure:

646

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 295Structure:

647

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 296Structure:

648

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 297Structure:

649

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 298Structure:

650

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 299Structure:

651

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 300Structure:

652

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 301Structure:

653

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 302Structure:

654

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 303Structure:

655

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 304Structure:

656

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 305Structure:

657

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless prismsSolvent for recrystallization: Acetone/n-hexaneM.p. 251-253° C.Form: FreeExample 306Structure:

658

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 128-131° C.Form: FreeExample 307Structure:

659

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 308Structure:

660

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless prismsSolvent for recrsytallization: EthanolM.p. 224-225° C.Form: FreeExample 309Structure:

661

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 310Structure:

662

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 311Structure:

663

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 312Structure:

664

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 313Structure:

665

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 314Structure:

666

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 315Structure:

667

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: White powderForm: FreeExample 316Structure:

668

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless prismsSolvent for recrystallization: Acetone/n-hexaneM.p. 124-128° C.Form: FreeExample 317Structure:

669

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: White powderForm: FreeExample 318Structure:

670

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 319Structure:

671

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 320Structure:

672

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 321Structure:

673

X: —CH2—R1: HR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 322Structure:

674

X: —CH2—R1: HR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 323Structure:

675

X: —CH2—R1: HR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 324Structure:

676

X: —CH2—R1: HR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 325Structure:

677

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 326Structure:

678

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 327Structure:

679

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 328Structure:

680

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 329Structure:

681

X: —CH2—R1: HR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 330Structure:

682

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 203-204° C.Form: FreeExample 331Structure:

683

X: —CH2—R1: H

684

R3: HCrystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 255-258° C.Form: HydrochlorideExample 332Structure:

685

X: —CH2—R1: HR2: —CH2CONHC2H5R3: HCrystalline form: Colorless amorphousForm: FreeExample 333Structure:

686

X: —CH2—R1: 7-Cl

687

R3: HCrystalline form: Colorless oilForm: FreeExample 334Structure:

688

X: —CH2—R1: 7-Cl

689

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 335Structure:

690

X: ═CH—R1: 7-Cl

691

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 336Structure:

692

X: ═CH—R1: 7-Cl

693

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 337Structure:

694

X: ═CH—R1: 7-ClR2: —CH2CONH(CH2)2N(C2H5)2R3: HCrystalline form: Colorless amorphousForm: FreeExample 338Structure:

695

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: White powderM.p. 102-106° C.Form: FreeExample 339Structure:

696

X: —CH2—R1: H

697

R3: HCrystalline form: Colorless amorphousForm: FreeExample 340Structure:

698

X: —CH2—R1: H

699

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 341Structure:

700

X: —CH2—R1: H

701

R3: HCrystalline form: Colorless amorphousForm: FreeExample 342Structure:

702

X: —CH2—R1: H

703

R3: HCrystalline form: Colorless amorphousForm: FreeExample 301Structure:

704

X: —CH2—R1: H

705

R3: HCrystalline form: Colorless needlesSolvent for recrystallization: Dichloromethane/ethanol/diethyl etherM.p. 190-193° C.Form: FreeExample 344Structure:

706

X: —CH2—R1: H

707

R3: HCrystallline form: Coloreless oilForm: FreeExample 345Structure:

708

X: —CH2—R1: 7-Cl

709

R3: HCrystalline form: Colorless viscous oilForm: FreeExample 346Structure:

710

X: —CH2—R1: H

711

R3: HCrystalline form: Colorless amorphousForm: FreeExample 347Structure:

712

X: —CH2—R1: 7-Cl

713

R3: HCrystalline form: White powderSolvent for recrystallization: Dichloromethane/diethyl etherM.p. 180-182° C. ° C.Form: FreeExample 348Structure:

714

X: —CH2—R1: 7-Cl

715

R3: HCrystalline form: Yellow powderSolvent for recrystallization: Ethanol/dichloromethane/diethyl etherM.p. 239-241° C.Form: FreeExample 349Structure:

716

X: —CH2—R1: 7-ClR2: —CH2CONHC2H5R3: HCrystalline form: Colorless prismsSolvent for recrystallization: Dichloromethane/ethanol/diethyl etherM.p. 252-254° C.Form: FreeExample 350Structure:

717

X: —CH2—R1: 7-Cl

718

R3: HCrystalline form: Colorless viscous oilForm: FreeExample 309Structure:

719

X: ═CH—R1: 7-ClR2: —CH2CO2C2H5R3: HCrystalline form: Pale yellow powderM.p. 71-75° C.Form: FreeExample 352Structure:

720

X: ═CH—R1: 7-ClR2: —CH2CO2C2H5R3: HCrystalline form: Pale yellow oilForm: FreeExample 353Structure:

721

X: ═CH—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: White powderForm: FreeExample 354Structure:

722

X: ═CH—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: White powderForm: FreeExample 355Structure:

723

X: —CH2—R1: HR2: —CH2CO2CH3R3: HCrystalline form: White powderM.p. 63-69° C.Form: FreeExample 356Structure:

724

X: —CH2—R1: HR2: —CH2CO2CH3R3: HCrystalline form: White powderForm: FreeExample 357Structure:

725

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Pale yellow powderForm: FreeExample 358Structure:

726

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless viscous oilForm: FreeExample 359Structure:

727

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless viscous oilForm: FreeExample 360Structure:

728

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless viscous oilForm: FreeExample 361Structure:

729

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 362Structure:

730

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 363Structure:

731

X: —CH2—R1: HR2 and R3: ═OCrystalline form: Pale yellow amorphousForm: FreeExample 364Structure:

732

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Pale yellow powderSolvent for recrystallization: Dichloromethane/methanol/diethyl etherM.p. 194-197° C.Form: FreeExample 365Structure:

733

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: White powderForm: FreeExample 366Structure:

734

X: —CH2—R1: H

735

R3: HCrystalline form: Colorless amorphousForm: FreeExample 367Structure:

736

X: —CH2—R1: 7-Cl

737

R3: HCrystalline form: Colorless amorphousForm: FreeExample 368Structure:

738

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: White powderSolvent for recrystallization: n-Hexane/ethyl acetateM.p. 134-136° C.Form: FreeExample 369Structure:

739

X: —CH2—R1: HR2: —CH2CO2CH3R3: HCrystalline form: White powderSolvent for recrystallization: n-Hexane/ethyl acetateM.p. 97-100° C.Form: FreeExample 370Structure:

740

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 371Structure:

741

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 372Structure:

742

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless needlesSolvent for recrystallization: Diethyl ether/n-hexaneM.p. 135-138° C.Form: FreeExample 373Structure:

743

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: White powderSolvent for recrystallization: Ethyl acetateM.p. 136-139° C.Form: FreeExample 374Structure:

744

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: White powderSolvent for recrystallization: Diethyl ether/ethyl acetateM.p. 143-145° C.Form: FreeExample 375Structure:

745

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 376Structure:

746

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: White powderSolvent for recrystallization: Diethyl ether/ethyl acetateM.p. 123-125° C.Form: FreeExample 377Structure:

747

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 378Structure:

748

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: White powderSolvent for recrystallization: n-Hexane/ethyl acetateM.p. 164-166° C.Form: FreeExample 379Structure:

749

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 380Structure:

750

X: —CH2—R1: 7-ClR2: —CH2COOCH3R3: HCrystalline form: White powderSolvent for recrystallization: n-Hexane/ethyl acetateM.p. 168-170° C.Form: FreeExample 381Structure:

751

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: White powderSolvent for recrystallization: Dichloromethane/n-hexaneM.p. 226-229° C.Form: FreeExample 382Structure:

752

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: White powderSolvent for recrystallization: n-Hexane/ethyl acetateM.p. 131-134° C.Form: FreeExample 383Structure:

753

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 384Structure:

754

X: —CH2—R1: HR2: —CH2CO2CH3R3: HCrystalline form: Pale yellow powderSolvent for recrystallization: n-Hexane/ethyl acetateM.p. 133-134.5° C.Form: FreeExample 385Structure:

755

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 386Structure:

756

X: —CH2—R1: 7-Cl

757

R3: HCrystalline form: Colorless viscous oilForm: FreeExample 387Structure:

758

X: —CH2—R1: 7-Cl

759

R3: HCrystalline form: Colorless amorphousForm: FreeExample 388Structure:

760

X: —CH2—R1: 7-ClR2: —CH2CONH(CH2)2N(C2H5)2R3: HCrystalline form: Colorless amorphousForm: FreeExample 389Structure:

761

X: —CH2—R1: 7-Cl

762

R3: HCrystalline form: Colorless amorphousForm: FreeExample 390Structure:

763

X: —CH2—R1: 7-ClR2: —CH2CONH(CH2)2N(C2H5)2R3: HCrystalline form: Colorless amorphousForm: FreeExample 391Structure:

764

X: —CH2—R1: 7-Cl

765

R3: HCrystalline form: Colorless amorphousForm: FreeExample 392Structure:

766

X: —CH2—R1: 7-ClR2: —CH2CONH(CH2)2N(C2H5)2R3: HCrystalline form: Colorless amorphousForm: FreeExample 393Structure:

767

X: —CH2—R1: 7-Cl

768

R3: HCrystalline form: Colorless amorphousForm: FreeExample 394Structure:

769

X: —CH2—R1: 7-Cl

770

R3: HCrystalline form: Pale yellow amorphousForm: FreeExample 395Structure:

771

X: —CH2—R1: HR2: HR3: HCrystalline form: Colorless needlesSolvent for recrystallization: Ethyl acetate/n-hexaneM.p. 134-135.5° C.Form: FreeExample 396Structure:

772

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Colorless needlesSolvent for recrystallization: n-HexaneM.p. 108-110.5° C.Form: FreeExample 397Structure:

773

X: —CH2—R1: 7-Cl

774

R3: HCrystalline form: Colorless amorphousForm: FreeExample 398Structure:

775

X: —CH2—R1: H

776

R3: HCrystalline form: Color amporphousForm: FreeExample 399Structure:

777

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: EthanolM.p. 131-133° C.Form: FreeExample 400Structure:

778

X: —CH2—R1: HR2: HR3: HCrystalline form: Colorless flakesSolvent for recrystallization: EthanolM.p. 125-126° C.Form: FreeExample 401Structure:

779

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: EthanolM.p. 134-135° C.Form: FreeExample 402Structure:

780

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: EthanolM.p. 190-192° C.Form: FreeExample 403Structure:

781

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: EthanolM.p. 139-142° C.Form: FreeExample 404Structure:

782

X: —CH2—R1: 7-F

783

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 405Structure:

784

X: —CH2—R1: 7-ClR2 and R3: ═OCrystalline form: Pale brown powderM.p. 157-159° C.Form: FreeExample 406Structure:

785

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: MethanolM.p. 166-167° C.Form: FreeExample 407Structure:

786

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderM.p. 181-182° C.Form: FreeExample 408Structure:

787

X: —CH2—R1: 7-F

788

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 409Structure:

789

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherM.p. 108-109° C.Form: FreeExample 410Structure:

790

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherM.p. 104-106° C.Form: FreeExample 411Structure:

791

X: —CH2—R1: HR2 and R3: ═OCrystalline form: White powderSolvent for recrystallization: Chloroform/diethy etherM.p. 130-132° C.Form: FreeExample 412Structure:

792

X: —CH2—R1: HR2: —OHR3: HCrystalline form: Pale brown powderSolvent for recrystallization: Chloroform/diethyl etherM.p. 191-193° C.Form: FreeExample 413Structure:

793

X: —CH2—R1: HR2: —OCH3R3: HCrystalline form: Colorless viscous oilForm: FreeExample 414Structure:

794

X: —CH2—R1: HR2 and R3: ═CH2Crystalline form: White powderSolvent for recrystallization: Diethyl ether/n-hexaneM.p. 123-124° C.Form: FreeExample 415Structure:

795

X: —CH2—R1: HR2: —OHR3: —CH2OHCrystalline form: White powderSolvent for recrystallization: Chloroform/diethyl etherForm: FreeExample 416Structure:

796

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Chloroform/diethyl etherM.p. 194-197° C.Form: FreeExample 417Structure:

797

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Pale yellow amorphousForm: HydrochlorideExample 418Structure:

798

X: —CH2—R1: 7-Cl

799

R3: HCrystalline form: Colorless amorphousForm: FreeExample 419Structure:

800

X: —CH2—R1: 7-ClR2: —CH2CONHC2H5R3: HCrystalline form: Colorless amorphousForm: FreeExample 420Structure:

801

X: —CH2—R1: 7-Cl

802

R3: HCrystalline form: Colorless amorphousForm: FreeExample 421Structure:

803

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Pale brown amorphousForm: HydrochlorideExample 422Structure:

804

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Chloroform/diethyl etherForm: FreeExample 423Structure:

805

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Colorless viscous oilForm: FreeExample 424Structure:

806

X: —CH2—R1: 7-Cl

807

R3: HCrystalline form: Colorless amorphousForm: FreeExample 425Structure:

808

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderForm: FreeExample 426Structure:

809

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Pale brown amorphousForm: FreeExample 427Structure:

810

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Ethanol/diethyl etherM.p. 223-227° C.Form: HydrochlorideExample 428Structure:

811

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Chloroform/diethyl ether/n-hexaneM.p. 152-154° C.Form: FreeExample 429Structure:

812

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Chloroform/diethyl etherM.p. 166-168° C.Form: FreeExample 430Structure:

813

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Chloroform/diethyl etherM.p. 190-192° C.Form: FreeExample 431Structure:

814

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Pale yellow powderSolvent for recrystallization: Chloroform/diethyl etherM.p. 185-187° C.Form: FreeExample 432Structure:

815

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Pale brown powderSolvent for recrystallization: Ehtanol/diethyl etherM.p. 154-158° C.Form: FreeExample 433Structure:

816

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Pale brown amorphousForm: FreeExample 434Structure:

817

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Ethanol/diethyl etherM.p. 222-225° C.Form: HydrochlorideExample 435Structure:

818

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Colorless prismsSolvent for recrystallization: Ethanol/dichloromethane/diethyl etherM.p. 199-201° C.Form: FreeExample 436Structure:

819

X: —CH2—R1: 7-Cl

820

R3: HCrystalline form: Colorless viscous oilForm: FreeExample 437Structure:

821

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Chloroform/diethyl etherM.p. 173-175° C.Form: FreeExample 438Structure:

822

X: —CH2—R1: 7-Cl

823

R3: HCrystalline form: Colorless amorphousForm: FreeExample 439Structure:

824

X: —CH2—R1: 7-Cl

825

R3: HCrystalline form: White powderSolvent for recrystallization: Chloroform/diethyl etherM.p. 218-219° C.Form: FreeExample 440Structure:

826

X: —CH2—R1: 7-Cl

827

R3: HCrystalline form: Yellow viscous oilForm: FreeExample 441Structure:

828

X: —CH2—R1: 7-Cl

829

R3: HCrystalline form: Yellow oilForm: FreeExample 442Structure:

830

X: —CH2—R1: 7-Cl

831

R3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherM.p. 143-145° C.Example 443Structure:

832

X: —CH2—R1: 7-Cl

833

R3: HExample 444Structure:

834

X: —CH2—R1: 7-FR2: —OHR3: HCrystalline form: Colorless amorphousFrom: FreeExample 445Structure:

835

X: Single bondR1: 6-Cl

836

R3: HCrystalline form: Colorless amorphousFrom: FreeExample 446Structure:

837

X: Single bondR1: 6-Cl

838

R3: HCrystalline form: Colorless amorphousFrom: FreeExample 447Structure:

839

X: Single bondR1: 6-Cl

840

R3: HCrystalline form: Colorless amorphousFrom: FreeExample 448Structure:

841

X: Single bondR1: 6-Cl

842

R3: HCrystalline form: Colorless amorphousFrom: FreeExample 449Structure:

843

X: —CH2—R1: 7-ClR2: —CH2CONHCH2CONH2R3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherM.p. 208-209° C.Form: FreeExample 450Structure:

844

X: —CH2—R1: 7-Cl

845

R3: HCrystalline form: Colorless amorphousForm: FreeExample 451Structure:

846

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: White powderSolvent for recrystallization: Diethy etherM.p. 222-224° C.Form: FreeExample 452Structure:

847

X: —CH2—R1: 7-FR2 and R3: ═OCrystalline form: Colorless flakeSolvent for recrystallization: Diethyl etherM.p. 97-100° C.Form: FreeExample 453Structure:

848

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Colorless prismsSolvent for recrystallization: Diethyl etherM.p. 116-118° C.Form: FreeExample 454Structure:

849

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherM.p. 115-116° C.Form: FreeExample 455Structure:

850

X: —CH2—R1: 7-Cl

851

R3: HCrystalline form: Pale yellow amorphousForm: FreeExample 456Structure:

852

X: —CH2—R1: 7-Cl

853

R3: HCrystalline form: Pale yellow amorphousForm: FreeExample 457Structure:

854

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Chloroform/diethyl ether/n-hexaneM.p. 194-197° C.Form: FreeExample 458Structure:

855

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Pale brown powderSolvent for recrystallization: Chloroform/diethyl etherM.p. 150-154° C.Form: FreeExample 459Structure:

856

X: Singel bondR1: HR2: —CH2CONH(CH2)2N(C2H5)2R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 460Structure:

857

X: Single bondR1: H

858

R3: HCrystalline form: Slightly orange amorphousForm: DihydrochlorideExample 461Structure:

859

X: Single bondR1: 6-ClR2: —CH2CONH(CH2)2N(C2H5)2R3: HCrystalline form: Slightly yellow amorphousForm: FreeExample 462Structure:

860

X: Single bondR1: 6-Cl

861

R3: HCrystalline form: Colorless amorphousForm: FreeExample 463Structure:

862

X: Single bondR1: 6-ClR2: —CH2CONH(CH2)2N(C2H5)2R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 464Structure:

863

X: Single bondR1: 6-Cl

864

R3: HCrystalline form: Colorless amorphousForm: FreeExample 465Structure:

865

X: —CH2—R1: 7-Cl

866

R3: HCrystalline form: White powderM.p. 154-156° C.Form: FreeExample 466Structure:

867

X: —CH2—R1: 7-Cl

868

R3: HCrystalline form: White powderSolvent for recrystallization: Chloroform/diethyl etherM.p. 195-196° C.Form: FreeExample 467Structure:

869

X: —CH2—R1: 7-Cl

870

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 468Structure:

871

X: —CH2—R1: 7-Cl

872

R3: HExample 469Structure:

873

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 470Structure:

874

X: —CH2—R1: 7-Cl

875

R3: HCrystalline form: Colorless amorhpusForm: FreeExample 471Structure:

876

X: —CH2—R1: 7-Cl

877

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 472Structure:

878

X: —CH2—R1: 7-Cl

879

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 473Structure:

880

X: —CH2—R1: 7-Cl

881

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 474Structure:

882

X: —CH2—R1: 7-ClR2: —O(CH2)2NHSO2CH3R3: HCrystalline form: Pale yellow powderSolvent for recrystallization: Chloroform/diethyl etherM.p. 158-159° C.Form: FreeExample 475Structure:

883

X: —CH2—R1: 7-ClR2: —O(CH2)2NHSO2CH3R3: HCrystalline form: Pale yellow powderSolvent for recrystallization: Chloroform/diethyl etherM.p. 193-194° C.Form: FreeExample 476Structure:

884

X: —CH2—R1: 7-Cl

885

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 477Structure:

886

X: —CH2—R1: 7-ClR2: —CH2CONH2R3: HCrystalline form: Colorless amorphousForm: FreeExample 478Structure:

887

X: —CH2—R1: 7-Cl

888

R3: HCrystalline form: Colorless amorphousForm: FreeExample 479Structure:

889

X: —CH2—R1: 7-Cl

890

R3: HCrystalline form: Pale yellow amorphousForm: FreeExample 480Structure:

891

X: —CH2—R1: 7-Cl

892

R3: HCrystalline form: Pale yellow amorphousForm: FreeExample 481Structure:

893

X: —CH2—R1: 7-Cl

894

R3: HCrystalline form: Pale yellow amorphousForm: HydrochlorideExample 482Structure:

895

X: —CH2—R1: 7-Cl

896

R3: HCrystalline form: Pale yellow amorphousForm: HydrochlorideExample 483Structure:

897

X: —CH2—R1: 7-Cl

898

R3: HCrystalline form: White powderSolvent for recrystallization: Chloroform/diethyl etherM.p. 155-158° C.Form: FreeExample 484Structure:

899

X: —CH2—R1: 7-Cl

900

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 485Structure:

901

X: —CH2—R1: 7-Cl

902

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 486Structure:

903

X: —CH2—R1: 7-Cl

904

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 487Structure:

905

X: —CH2—R1: 7-Cl

906

R3: HCrystalline form: Colorless amorphousForm: FreeExample 488Structure:

907

X: —CH2—R1: 7-Cl

908

R3: HCrystalline form: Pale yellow amorphousForm: FreeExample 489Structure:

909

X: —CH2—R1: 7-Cl

910

R3: HCrystalline form: Pale yellow amorphousForm: HydrochlorideExample 490Structure:

911

X: —CH2—R1: 7-Cl

912

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 491Structure:

913

X: —CH2—R1: 7-ClR2: —CH2CONH(CH2)2N(C2H5)2R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 492Structure:

914

X: —CH2—R1: 7-Cl

915

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 493Structure:

916

X: —CH2—R1: 7-Cl

917

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 494Structure:

918

X: —CH2—R1: 7-ClR2: —CH2CONH(CH2)2N(C2H5)2R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 495Structure:

919

X: —CH2—R1: 7-Cl

920

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 496Structure:

921

X: —CH2—R1: 7-Cl

922

R3: HCrystalline form: Colorless amorphousForm: FreeExample 497Structure:

923

X: —CH2—R1: 7-Cl

924

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 498Structure:

925

X: —CH2—R1: 7-Cl

926

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 499Structure:

927

X: —CH2—R1: 7-Cl

928

R3: HCrystalline form: Pale yellow amorphousForm: HydrochlorideExample 500Structure:

929

X: —CH2—R1: 7-Cl

930

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 501Structure:

931

X: —CH2—R1: 7-Cl

932

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 502Structure:

933

X: —CH2—R1: 7-Cl

934

R3: HCrystalline form: Pale yellow amorphousForm: HydrochlorideExample 503Structure:

935

X: —CH2—R1: 7-Cl

936

R3: HCrystalline form: White powderSolvent for recrystallization: Chloroform/diethyl etherForm: FreeExample 504Structure:

937

X: —CH2—R1: 7-Cl

938

R3: HCrystalline form: Pale yellow amorphousForm: HydrochlorideExample 505Structure:

939

X: —CH2—R1: 7-Cl

940

R3: HCrystalline form: Pale brown powderForm: FreeExample 506Structure:

941

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Chloroform/diethyl etherM.p. 209-211° C.Form: FreeExample 507Structure:

942

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Chloroform/diethyl etherM.p. 169-170° C.Form: FreeExample 508Structure:

943

X: —CH2—R1: 7-ClR2:—CH2CONHC2H5R3: HCrystalline form: Colorless amorphousForm: FreeExample 509Structure:

944

X: —CH2—R1: H

945

R3: HCrystalline form: Colorless amorphousForm: FreeExample 510Structure:

946

X: —CH2—R1: H

947

R3: HCrystalline form: Colorless amorphousForm: FreeExample 511Structure:

948

X: —CH2—R1: H

949

R3: HCrystalline form: Colorless amorphousForm: FreeExample 512Structure:

950

X: —CH2—R1: H

951

R3: HCrystalline form: Colorless amorphousForm: FreeExample 513Structure:

952

X: —CH2—R1: H

953

R3: HCrystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 204-207° C.Form: HydrochlorideExample 514Structure:

954

X: —CH2—R1: H

955

R3: HCrystalline form: White powderSolvent for recrystallization: Acetone/n-hexaneM.p. 217-220° C.Form: HydrochlorideExample 515Structure:

956

X: —CH2—R1: HR2: HR3: HCrystalline form: Yellow needlesSolvent for recrystallization: WaterM.p. 198-202° C.Form: HydroiodideExample 516Structure:

957

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Chloroform/diethyl etherForm: FreeExample 517Structure:

958

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Chloroform/diethyl etherForm: FreeExample 518Structure:

959

X: —CH2—R1: 7-Cl

960

R3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherM.p. 154-155° C.Form: FreeExample 519Structure:

961

X: —CH2—R1: 7-Cl

962

R3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherM.p. 188-190° C.Example 520Structure:

963

X: —CH2—R1: 7-Cl

964

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 521Structure:

965

X: —CH2—R1: H

966

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 522Structure:

967

X: —CH2—R1: H

968

R3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherM.p. 149-151° C.Example 523Structure:

969

X: —CH2—R1: HR2: HR3: HCrystalline form: Yellow amorphousForm: FreeExample 524Structure:

970

X: —CH2—R1: HR2: HR3: HCrystalline form: Colorless amorphousForm: FreeExample 525Structure:

971

X: —CH2—R1: 7-Cl

972

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 526Structure:

973

X: —CH2—R1: 7-Cl

974

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 527Structure:

975

X: —CH2—R1: HR2: HR3: HCrystalline form: Brown powderSovelnt for recrystallization: Diethyl etherM.p. 155-159° C. (decomposed)Form: HydrochlorideExample 528Structure:

976

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSovelnt for recrystallization: Diethyl etherM.p. 142-145° C.Form: FreeExample 529Structure:

977

X: —CH2—R1: H

978

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 530Structure:

979

X: —CH2—R1: HR2: HR3: HCrystalline form: Pale yellow powderSolvent for recrystallization: Chloroform/diethyl ether/n-hexaneForm: FreeExample 531Structure:

980

X: —CH2—R1: H

981

R3: HCrystalline form: Colorless amorphousForm: Dihydrochloride Example 532Structure:

982

X: —CH2—R1: HR2: —CH2CNR3: HCrystalline form: Colorless amorphousForm: FreeExample 533Structure:

983

X: —CH2—R1: H

984

R3: HCrystalline form: White powderSolvent for recrystallization: Dichloromethane/diethyl etherM.p. 191-194° C.Form: FreeExample 534Structure:

985

X: —CH2—R1: HR2: HR3: HCrystalline form: Pale brown amorphousForm: FreeExample 535Structure:

986

X: —CH2—R1: 7-Cl

987

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 536Structure:

988

X: —CH2—R1: H

989

R3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherM.p. 146-147° C.Example 537Structure:

990

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: EthanolM.p. 201-202° C.Form: FreeExample 538Structure:

991

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderM.p. 118-120° C.Form: FreeExample 539Structure:

992

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Ethanol/diisopropyl etherM.p. 173-174.5° C.Form: FreeExample 540Structure:

993

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderM.p. 159-161° C.Form: FreeExample 541Structure:

994

X: —CH2—R1: 7-Cl

995

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 542Structure:

996

X: —CH2—R1: HR2: HR3: HCrystalline form: Colorless amorphousForm: FreeExample 543Structure:

997

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: n-HexaneM.p. 94-95° C.Form: FreeExample 544Structure:

998

X: —CH2—R1: 7-F

999

R3: HCrystalline form: Coloreless amorphousForm: HydrochlorideExample 545Structure:

1000

X: —CH2—R1: H

1001

R3: HCrystalline form: Coloreless amorphousForm: HydrochlorideExample 546Structure:

1002

X: —CH2—R1: H

1003

R3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherM.p. 174-176° C.Form: FreeExample 547Structure:

1004

X: —CH2—R1: H

1005

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 548Structure:

1006

X: —CH2—R1: H

1007

R3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherM.p. 133-135° C.Form: FreeExample 549Structure:

1008

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderM.p. 181-184° C.Form: FreeExample 550Structure:

1009

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Methanol/diethyl etherM.p. 197-200° C.Form: FreeExample 551Structure:

1010

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Ethyl acetateM.p. 162-163.5° C.Form: FreeExample 552Structure:

1011

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderM.p. 168-171°C.Form: FreeExample 553Structure:

1012

X: —CH2—R1: H

1013

R3: HCrystalline form: Colorless amorphousForm: FreeExample 554Structure:

1014

X: —CH2—R1: H

1015

R3: HCrystalline form: Colorless amorphousForm: FreeExample 555Structure:

1016

X: —CH2—R1: HR2: HR3: HCrystalline form: Colorless amorphousForm: FreeExample 556Structure:

1017

X: —CH2—R1: HR2: HR3: HCrystalline form: Colorless amorphousForm: FreeExample 557Structure:

1018

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherM.p. 150-152° C.Form: TrifluoroacetateExample 558Structure:

1019

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderForm: FreeExample 559Structure:

1020

X: —CH2—R1: H

1021

R3: HCrystalline form: White powderSolvent for recrystallization: Diisopropyl etherForm: FreeExample 560Structure:

1022

X: —CH2—R1: HR2: HR3: HCrystalline form: Slightly orange amorphousForm: HydrochlorideExample 561Structure:

1023

X: —CH2—R1: HR2: CH2COOHR3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherM.p. 186-188° C.Form: FreeExample 562Structure:

1024

X: —CH2—R1: H

1025

R3: HCrystalline form: Yellow amorphousForm: FreeExample 563Structure:

1026

X: —CH2—R1: H

1027

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 564Structure:

1028

X: —CH2—R1: HR2: —CH2CONHC2H5R3: HCrystalline form: Colorless amorphousForm: FreeExample 565Structure:

1029

X: —CH2—R1: H

1030

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 566Structure:

1031

X: —CH2—R1: HR2: —CH2CON(CH2CH2OH)2R3: HCrystalline form: Colorless amorphousForm: FreeExample 567Structure:

1032

X: —CH2—R1: H

1033

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 568Structure:

1034

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherM.p. 144-146° C.Form: FreeExample 569Structure:

1035

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherM.p. 128-130° C.Form: FreeExample 570Structure:

1036

X: —CH2—R1: HR2: —CH2COOCH3R3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherM.p. 110-111° C.Form: FreeExample 571Structure:

1037

X: —CH2—R1: H

1038

R3: HCrystalline form: White powderSolvent for recrystallization: Acetone/diethyl etherM.p. 161.5-163° C.Form: HydrochlorideExample 572Structure:

1039

X: —CH2—R1: HR2: —CH2CONHC2H5R3: HCrystalline form: Colorless amorphousForm: FreeExample 573Structure:

1040

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Diisopropyl etherM.p. 160-162° C.Form: FreeExample 574Structure:

1041

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Ethanol/ethyl acetate/n-hexaneM.p. 108-109° C.Form: FreeExample 575Structure:

1042

X: —CH2—R1: HR2: —CH2OHR3: HCrystalline form: White powderSolvent for recrystallization: Chloroform/diethyl etherM.p. 104-106° C.Form: FreeExample 576Structure:

1043

X: —CH2—R1: HR2: —CH2OCOCH3R3: HCrystalline form: White powderSolvent for recrystallization: Chloroform/diethyl etherM.p. 115-116° C.Form: FreeExample 577Structure:

1044

X: —CH2—R1: HR2: HR3: HCrystalline form: Colorless amorphousForm: FreeExample 578Structure:

1045

X: —CH2—R1: HR2: HR3: HCrystalline form: Colorless amorphousForm: FreeExample 579Structure:

1046

X: —CH2—R1: HR2: HR3: HCrystalline form: Pale yellow powderSolvent for recrystallization: n-Hexane/ethyl acetateM.p. 201.5-203° C.Form: FreeExample 580Structure:

1047

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: n-Hexane/ethyl acetateM.p. 196-198° C.Form: FreeExample 581Structure:

1048

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Diethyl ether/n-hexaneM.p. 130-133° C.Form: FreeExample 582Structure:

1049

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Ethyl acetate/n-hexaneM.p. 125-127° C.Form: FreeExample 583Structure:

1050

X: —CH2—R1: H

1051

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 584Structure:

1052

X: —CH2—R1: HR2: —CH2CONHC2H5R3: HCrystalline form: Colorless amorphousForm: FreeExample 585Structure:

1053

X: —CH2—R1: H

1054

R3: HCrystalline form: Colorless amorphousForm: FreeExample 586Structure:

1055

X: —CH2—R1: 7-ClR2: —OCH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 587Structure:

1056

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderM.p. 196-198° C.Form: FreeExample 588Structure:

1057

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: MethanolM.p. 169-170° C.Form: FreeExample 589Structure:

1058

X: —CH2—R1: HR2: HR3: HCrystalline form: Slightly yellow amorphousForm: FreeExample 590Structure:

1059

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: EthanolM.p. 218-220° C.Form: FreeExample 591Structure:

1060

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: EthanolM.p. 194-195° C.Form: FreeExample 592Structure:

1061

X: —CH2—R1: HR2: HR3: HCrystalline form: Pale yellow powderSolvent for recrystallization: n-Hexane/ethyl acetateM.p. 158-159° C.Form: FreeExample 593Structure:

1062

X: —CH2—R1: HR2: —OCH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 594Structure:

1063

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderForm: FreeExample 595Structure:

1064

X: —CH2—R1: HR2: —N(C2H5)2R3: HCrystalline form: Yellow amorphousForm: FreeExample 596Structure:

1065

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallizatin: Diisopropyl etherM.p. 205-206° C.Form: FreeExample 597Structure:

1066

X: —CH2—R1: 7-ClR2: —OHR3: —CH2OHCrystalline form: White powderSolvent for recrystallization: Chloroform/diethyl etherM.p. 142-144° C.Form: FreeExample 598Structure:

1067

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherM.p. 132-135° C.Form: FreeExample 599Structure:

1068

X: —CH2—R1: H

1069

R3: HCrystalline form: Pale yellow amorphousForm: HydrochlorideExample 600Structure:

1070

X: —CH2—R1: HR2: —CH2CONH2R3: HCrystalline form: Pale brown powderSolvent for recrystallization: Chloroform/diethyl etherM.p. 119-121° C.Form: HydrochlorideExample 601Structure:

1071

X: —CH2—R1: HR2: —CH2CONH—OCH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 602Structure:

1072

X: —CH2—R1: 7-ClR2: —OHR3: HCrystalline form: White powderSolvent for recrystallization: Chloroform/diethyl etherM.p. 175-178° C.Form: FreeExample 603Structure:

1073

X: —CH2—R1: HR2 and R3: ═CH2Crystalline form: Pale yellow powderSolvent for recrystallization: Diisopropyl ether/n-hexaneM.p. 113-115° C.Form: FreeExample 604Structure:

1074

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderM.p. 128-130° C.Form: FreeExample 605Structure:

1075

X: —CH2—R1: 7-ClR2: —O(CH2)2NHSO2CH3R3: HCrystalline form: Pale yellow powderSolvent for recrystallization: Chloroform/diethyl etherM.p. 182-183° C.Form: FreeExample 606Structure:

1076

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless oilForm: FreeExample 607Structure:

1077

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless oilForm: FreeExample 608Structure:

1078

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Yellow amorphousForm: FreeExample 609Structure:

1079

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Yellow amorphousForm: FreeExample 610Structure:

1080

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Yellow amorphousForm: FreeExample 611Structure:

1081

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Brown amorphousForm: FreeExample 612Structure:

1082

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Pale brown powderSolvent for recrystallization: Chloroform/diethyl etherM.p. 149-151° C.Form: FreeExample 613Structure:

1083

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Pale brown amorphousForm: FreeExample 614Structure:

1084

X: —CH2—R1: 7-Cl

1085

R3: HCrystalline form: Pale yellow amorphousForm: FreeExample 615Structure:

1086

X: —CH2—R1: 7-Cl

1087

R3: HCrystalline form: Colorless oilForm: FreeExample 616Structure:

1088

X: —CH2—R1: 7-Cl

1089

R3: HCrystalline form: Colorless amorphousForm: FreeExample 617Structure:

1090

X: —CH2—R1: 7-Cl

1091

R3: HCrystalline form: Pale brown oilForm: FreeExample 618Structure:

1092

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Pale yellow oilForm: FreeExample 619Structure:

1093

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 620Structure:

1094

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Pale yellow powderSolvent for recrystallization: Chloroform/diethyl etherM.p. 151-161° C.Example 621Structure:

1095

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: White powderSolvent for recrystallization: Methanol/diethyl etherM.p. 258-260° C.Form: HydrochlorideExample 622Structure:

1096

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 623Structure:

1097

X: —CH2—R1: H

1098

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 624Structure:

1099

X: —CH2—R1: HR2: —CH2CO2CH3R3: HCrystalline form: Coloreless amorphousForm: FreeExample 625Structure:

1100

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherM.p. 188-189° C.Form: FreeExample 626Structure:

1101

X: —CH2—R1: 7-FR2: —CH2COOCH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 627Structure:

1102

X: —CH2—R1: HR2: —CH2COOCH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 628Structure:

1103

X: —CH2—R1: HR2: —CH2COOCH3R3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherM.p. 178-179° C.Form: FreeExample 629Structure:

1104

X: —CH2—R1: 7-FR2: —CH2COOCH3R3: HCrystalline form: Colorless oilForm: FreeExample 630Structure:

1105

X: —CH2—R1: HR2: —CH2COOCH3R3: HCrystalline form: Colorless oilForm: FreeExample 631Structure:

1106

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: White powderForm: FreeExample 632Structure:

1107

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 633Structure:

1108

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 634Structure:

1109

X: —CH2—R1: 7-FR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 635Structure:

1110

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderM.p. 138-140° C.Form: FreeExample 636Structure:

1111

X: —CH2—R1: 7-ClR2: —CH2CO2HR3: HCrystalline form: White powderSolvent for recrystallizatin: Ethanol/diethyl etherM.p. 208-211° C.Form: FreeExample 637Structure:

1112

X: —CH2—R1: HR2: —CH2CO2CH3R3: HCrystalline form: Pale brown oilForm: FreeExample 638Structure:

1113

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: Pale brown powderSolvent for recrystallization: Chloroform/diethyl etherM.p. 192-194° C.Form: FreeExample 639Structure:

1114

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: White powderSolvent for recrystallization: Ethanol/diethyl etherM.p. 238-239° C.Form: HydrochlorideExample 640Structure:

1115

X: —CH2—R1: 7-ClR2: —CH2COOCH3R3: HCrystalline form: Pale yellow solidForm: FreeExample 641Structure:

1116

X: —CH2—R1: 7-ClR2: —CH2COOCH3R3: HCrystalline form: White powderM.p. 82-87° C.Form: FreeExample 642Structure:

1117

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: White powderM.p. 121-127° C.Form: FreeExample 643Structure:

1118

X: —CH2—R1: HR2: —CH2COOCH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 644Structure:

1119

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 645Structure:

1120

X: —CH2—R1: HR2: —CH2COOCH3R3: HCrystalline form: White powderForm: FreeExample 646Structure:

1121

X: —CH2—R1: HR2: —CH2COOCH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 647Structure:

1122

X: —CH2—R1: HR2: —CH2COOCH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 648Structure:

1123

X: —CH2—R1: HR2: —CH2COOCH3R3: HCrystalline form: Brown amorphousForm: FreeExample 649Structure:

1124

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: White powderForm: FreeExample 650Structure:

1125

X: Single bondR1: 6-ClR2 and R3: ═OCrystalline form: Slightly yellow powderForm: FreeExample 651Structure:

1126

X: Single bondR1: 6-ClR2 and R3: ═CH—CO2C2H5Crystalline form: Slightly yellow amorphousForm: FreeExample 652Structure:

1127

X: Single bondR1: 6-ClR2: —CH2CO2C2H5R3: HCrystalline form: Slightly yellow amorphousForm: FreeExample 653Structure:

1128

X: Single bondR1: 6-ClR2 and R3: ═OCrystalline form: Yellow solidForm: FreeExample 654Structure:

1129

X: Single bondR1: 6-ClR2 and R3: ═OCrystalline form: Yellow powderForm: FreeExample 655Structure:

1130

X: Single bondR1: 6-ClR2: —CH2CO2HR3: HCrystalline form: Colorless amorphousForm: FreeExample 656Structure:

1131

X: Single bondR1: 6-ClR2 and R3: ═CH—COOC2H5Crystalline form: White powderForm: FreeExample 657Structure:

1132

X: Single bondR1: 6-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 658Structure:

1133

X: Single bondR1: 6-ClR2: —CH2CO2CH3R3: HCrystalline form: Yellow powderForm: FreeExample 659Structure:

1134

X: Single bondR1: 6-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 660Structure:

1135

X: Single bondR1: 6-ClR2: —CH2CO2CH3R3: HCrystalline form: White powderForm: FreeExample 661Structure:

1136

X: Single bondR1: 6-ClR2: —CH2CO2CH3R3: HCrystalline form: Coloreless amorphousForm: FreeExample 662Structure:

1137

X: Single bondR1: 6-ClR2: —CH2COOHR3: HCrystalline form: Coloreless amorphousForm: FreeExample 663Structure:

1138

X: Single bondR1: 6-ClR2: —CH2CO2CH3R3: HCrystalline form: Coloreless amorphousForm: FreeExample 664Structure:

1139

X: Single bondR1: 6-ClR2: —CH2CO2CH3R3: HCrystalline form: Red amorphousForm: FreeExample 665Structure:

1140

X: Single bondR1: 6-ClR2: —CH2COOHR3: HCrystalline form: Yellow amorphousForm: FreeExample 666Structure:

1141

X: Single bondR1: 6-ClR2: —CH2COOCH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 667Structure:

1142

X: Single bondR1: 6-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 668Structure:

1143

X: Single bondR1: 6-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 669Structure:

1144

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 670Structure:

1145

X: —CH2—R1: 7-ClR2: —CH2COOCH3R3: HCrystalline form: Slightly red powderForm: FreeExample 671Structure:

1146

X: —CH2—R1: HR2: —CH2COOCH3R3: HCrystalline form: White powderForm: FreeExample 672Structure:

1147

X: —CH2—R1: HR2: HR3: HCrystalline form: Slightly red powderForm: FreeExample 673Structure:

1148

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 674Structure:

1149

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 675Structure:

1150

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 676Structure:

1151

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 677Structure:

1152

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 678Structure:

1153

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 679Structure:

1154

X: —CH2—R1: HR2: —CH2COOCH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 680Structure:

1155

X: —CH2—R1: HR2: —CH2COOCH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 681Structure:

1156

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: White powderSolvent for recrystallization: Ethanol/diethyl etherM.p. 183-183.5° C.Form: FreeExample 682Structure:

1157

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: White powderSolvent for recrystallization: Ethanol/diethyl etherM.p. 169.5-170° C.Form: FreeExample 683Structure:

1158

X: —CH2—R1: 7-ClR2: —OCH2COOCH3R3: HCrystalline form: Slightly yellow powderForm: FreeExample 684Structure:

1159

X: —CH2—R1: HR2: —CH2COOCH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 685Structure:

1160

X: —CH2—R1: HR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 686Structure:

1161

X: —CH2—R1: HR2: —CH2CO2CH3R3: HCrystalline form: Slightly yellow powderForm: FreeExample 687Structure:

1162

X: —CH2—R1: HR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 688Structure:

1163

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: White powderSolvent for recrystallization: Ethanol/diethyl etherM.p. 176-177° C.Form: FreeExample 689Structure:

1164

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 690Structure:

1165

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: Slightly yellow powderForm: FreeExample 691Structure:

1166

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: Free

[0794] The suitable starting compounds are treated in the same manner as in Examples 1 and 2 to give the following compounds.

1167

Example 692Structure:

1168

1169

R1: HR2 and R3: ═OCrystalline form: Colorless amorphousForm: FreeExample 693Structure:

1170

1171

R1: HR2 and R3: ═OCrystalline form: Colorless amorphousForm: FreeExample 694Structure:

1172

1173

R1: HR2 and R3: ═OCrystalline form: White powderM.p. 166-170° C.Form: FreeExample 695Structure:

1174

1175

R1: HR2 and R3: ═OCrystalline form: White powderSolvent for recrystallization: Diethyl etherM.p. 215-218° C. (decomposed)Form: FreeExample 696Structure:

1176

1177

R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherM.p. 182-188° C. (decomposed)Form: FreeExample 697Structure:

1178

1179

R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherM.p. 105-108° C.Form: FreeExample 698Structure:

1180

1181

R1: HR2 and R3: ═OCrystalline form: White powderM.p. 154-158° C.Form: FreeExample 699Structure:

1182

1183

R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherM.p. 144-145° C.Example 700Structure:

1184

1185

R1: HR2: HR3: HCrystalline form: Pale yellow powderForm: FreeExample 701Structure:

1186

1187

R1: HR2 and R3: ═OCrystalline form: Brown powderForm: FreeExample 702Structure:

1188

1189

R1: HR2 and R3: ═OCrystalline form: Colorless powderForm: FreeExample 703Structure:

1190

1191

R1: HR2: HR3: HCrystalline form: Pale yellow oilForm: FreeExample 704Structure:

1192

1193

R1: HR2 and R3: ═OCrystalline form: Colorless amorphousForm: FreeExample 705Structure:

1194

1195

R1: HR2 and R3: ═OCrystalline form: Colorless amorphousForm: FreeExample 706Structure:

1196

1197

R1: HR2 and R3: ═OCrystalline form: Colorless amorphousForm: FreeExample 707Structure:

1198

1199

R1: HR2 and R3: ═OCrystalline form: White powderForm: FreeExample 708Structure:

1200

1201

R1: HR2 and R3: ═OCrystalline form: Colorless amorphousForm: FreeExample 709Structure:

1202

1203

R1: HR2 and R3: ═OCrystalline form: White powderForm: FreeExample 710Structure:

1204

1205

R1: HR2 and R3: ═OCrystalline form: Yellow amorphousForm: FreeExample 711Structure:

1206

1207

R1: HR2 and R3: ═OCrystalline form: Colorless amorphousForm: FreeExample 712Structure:

1208

1209

R1: HR2 and R3: ═OCrystalline form: White powderForm: FreeExample 713Structure:

1210

1211

R1: HR2: HR3: HCrystalline form: Colorless amorphousForm: FreeExample 714Structure:

1212

1213

R1: HR2: HR3: HCrystalline form: Colorless prismsForm: FreeExample 715Structure:

1214

1215

R1: HR2 and R3: ═OCrystalline form: Yellow amorphousForm: FreeExample 716Structure:

1216

1217

R1: HR2 and R3: ═OCrystalline form: Colorless amorphousForm: FreeExample 717Structure:

1218

1219

R1: HR2 and R3: ═OCrystalline form: Yellow amorphousForm: FreeExample 718Structure:

1220

1221

R1: HR2 and R3: ═OCrystalline form: White powderForm: FreeExample 719Structure:

1222

1223

R1: HR2 and R3: ═OCrystalline form: Yellow amorphousForm: FreeExample 720Structure:

1224

1225

R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherM.p. 120-123° C.Form: Free

[0795] The data of NMR analysis of the compounds of the above Examples are as follows.

[0796] NMR analysis:

[0797] The compound of Example 147 1H-NMR (200 MHz, CDCl3) δ ppm: 1.35-3.55, 4.50-5.10 [total 16H, m, 2.20 (s), 2.39 (s), 4.69 (s)], 6.54 (1H, d, J=8.27 Hz), 6.71 (1H, d, J=12.82 Hz), 6.78-6.95 (1H, m), 7.05-7.50, 7.75-8.20 (total 3H, m)

[0798] The compound of Example 148 1H-NMR (200 MHz, CDCl3) δ ppm: 0.98-3.94, 4.41-4.61 and 5.03-5.19 [all 24H, m, 1.12 (t, J=6.67 Hz), 4.57 (s)], 6.38-7.52 and 8.16-8.38 (all 13H, m)

[0799] The compound of Example 150 1H-NMR (200 MHz, CDCl3) δ ppm: 0.86-3.91, 4.36-4.61 and 5.00-5.20 [all 27H, m, 1.12 (t, J=7.08 Hz), 2.34 (s), 4.54 (s)], 7.39-7.53 and 8.14-8.42 (all 12H, m)

[0800] The compound of Example 151 1H-NMR (200 MHz, CDCl3) δ ppm: 0.90-4.24, 4.52-4.81 and 5.08-5.24 [all 27H, m, 125 (t, J=7.27 Hz), 2.60 (s), 4.67 (s)], 6.48-7.71 and 8.25-8.62 (all 12H, m)

[0801] The compound of Example 152 1H-NMR (200 MHz, CDCl3) δ ppm: 0.93-4.18, 4.35-4.69 and 5.00-5.21 [all 27H, m, 1.12 (t, J=6.62 Hz), 2.30 (s), 4.53 (s)], 6.48-7.62 and 8.18-8.40 (all 12H, m)

[0802] The compound of Example 153 1H-NMR (200 MHz, CDCl3) δ ppm: 0.90-4.18, 4.35-4.70 and 5.05-5.18 [all 27H, m, 3.89 (s)], 6.45-8.12 and 8.90-9.25 (all 12H, m)

[0803] The compound of Example 154 1H-NMR (200 MHz, CDCl3) δ ppm: 0.95-3.91, 4.31-4.68 and 4.98-5.20 [all 27H, m, 1.12 (t, J=7.20 Hz), 3.80 (s), 4.53 (s)], 6.48-7.61 and 8.29-8.42 (all 12H, m)

[0804] The compound of Example 155 1H-NMR (200 MHz, CDCl3) δ ppm: 0.96-3.94, 4.40-4.62 and 5.00-5.20 [all 27H, m, 1.12 (t, J=7.18 Hz), 2.33 (s), 4.56 (s)], 6.50-7.60 and 8.34-8.48 (all 12H, m)

[0805] The compound of Example 156 1H-NMR (200 MHz, CDCl3) δ ppm: 0.96-3.92, 4.31-4.62 and 5.0-5.21 [all 27H, m, 1.12 (t, J=7.24 Hz), 3.77 (s), 4.50 (s)], 6.47-7.65 and 8.32-8.52 (all 12H, m)

[0806] The compound of Example 157 1H-NMR (200 MHz, CDCl3) δ ppm: 0.84-4.15, 4.39-4.62 and 5.05-5.40 [all 24H, m, 1.11 (t, J=5.70 Hz), 5.15 (s), 5.29 (s)], 6.54 (1H, d, J=6.48 Hz), 6.78 (1H, d, J=6.66 Hz), 6.98-7.75 and 7.95-8.12 [all 11H, m, 7.35 (s), 7.99 (s)]

[0807] The compound of Example 158 1H-NMR (200 MHz, CDCl3) δ ppm: 0.61 (3H, d, J=5.16 Hz), 0.97 (3H, d, J=5.28 Hz), 1.12-5.15 and 5.76-5.86 [all 15H, m, 2.51 (s), 4.63 (s)], 6.38-8.75 [all 12H, m, 8.47 (s)]

[0808] The compound of Example 159 1H-NMR (200 MHz, CDCl3) δ ppm: 1.11-4.20 and 4.31-4.62 [all 21H, m, 4.53 (s), 4.62 (s)], 2.46 (3H, s), 6.35-7.68 and 8.18-8.56 (all 12H, m)

[0809] The compound of Example 160 1H-NMR (200 MHz, CDCl3) δ ppm: 0.81-4.29, 4.31-4.71 and 4.95-5.13 (all 28H, m), 1.02 (t, J=5.66 Hz), 1.15 (J=5.78 Hz), 4.54 (s), 4.63 (s)], 6.35-7.76 and 8.23-8.69 (all 13H, m, 8.53 (s)]

[0810] The compound of Example 161 1H-NMR (200 MHz, CDCl3) δ ppm: 0.79-4.72 and 4.90-5.08 [all 22H, m, 2.45 (s), 4.51 (s), 4.61 (s)], 6.30-7.69 and 8.21-8.63 [all 12H, m, 6.38 (d, J=6.80 Hz), 6.50 (d, J=6.66 Hz), 8.53 (s)]

[0811] The compound of Example 162 1H-NMR (200 MHz, CDCl3) δ ppm: 0.72-4.01, 4.31-4.73 and 4.89-5.18 [all 14H, m, 2.50 (s), 4.52 (s), 4.64 (s), 5.04 (s)], 5.80-7.70 and 8.12-8.58 [all 12H, m, 6.54 (d, J=6.64 Hz), 8.42 (s)]

[0812] The compound of Example 163 1H-NMR (200 MHz, CDCl3) δ ppm: 0.81-3.59 [all 15H, m, 1.22 (t, J=5.96 Hz), 2.39 (s), 2.98 (q, J=5.94 Hz)], 4.75-5.05 (1H, m), 6.50-7.62 [all 8H, m, 6.60 (d, J=6.20 Hz), 6.85 (t, J=6.10 Hz), 7.01 (t, J=5.96 Hz), 7.56 (s)]

[0813] The compound of Example 165 1H-NMR (200 MHz, DMSO-d6) δ ppm: 0.36-1.15, 1.35-3.89 and 4.98-5.09 [all 30H, m, 2.27 (s), 2.29 (s)], 5.65-6.70 (all 11H, m)

[0814] The compound of Example 167 1H-NMR (200 MHz, CDCl3) δ ppm: 0.92 (6H, d, J=5.36 Hz), 1.35-3.13, 3.28-5-3.58, 3.69-4.01 and 4.82-5.09 [all 14H, m, 2.40 (s), 3.88 (d, J=5.24 Hz)], 6.42-7.40 [all 8H, m, 7.00 (t, J=5.84 Hz)]

[0815] The compound of Example 173 1H-NMR (200 MHz, CDCl3) δ ppm: 1.01-4.10, 4.41-4.68 and 4.92-5.15 [all 26H, m, 2.33 (s), 2.52 (s), 3.88 (s)], 6.35-7.60 [all 10H, m, 6.59 (d, J=8.35 Hz)]

[0816] The compound of Example 174 1H-NMR (200 MHz, CDCl3) δ ppm: 1.01-4.12, 4.45-4.70 and 4.92-5.16 [all 26H, m, 2.33 (s), 2.53 (s), 3.88 (s)], 6.41-7.63 (all 11H, m)

[0817] The compound of Example 175 1H-NMR (200 MHz, CDCl3) δ ppm: 0.52 (3H, d, J=6.52 Hz), 0.96 (3H, d, J=6.59 Hz), 1.05-2.15, 2.21-4.67 and 5.60-5.76 [all 16H, m, 2.59 (s), 3.88 (s)], 6.29-7.62 (all 11H, m)

[0818] The compound of Example 176 1H-NMR (200 MHz, CDCl3) δ ppm: 1.15-2.20, 2.49-4.61 and 5.01-5.28 [all 17H, m, 3.74 (s), 3.77 (s), 4.51 (s)], 6.38-7.60 and 8.21-8.49 [all 12H, m, 6.55 (d, J=8.32 Hz)]

[0819] The compound of Example 177 1H-NMR (200 MHz, CDCl3) δ ppm: 1.18-2.31, 2.51-3.96 and 4.26-5.51 [all 15H, m, 3.77 (s), 4.53 (s)], 6.40-6.69, 6.81-7.00, 7.08-7.51 and 8.25-8.41 (all 12H, m)

[0820] The compound of Example 179 1H-NMR (200 MHz, CDCl3) δ ppm: 1.21-2.30, 2.55-3.96 and 4.25-5.80 [all 15H, m, 3.76 (s), 4.49 (s)], 6.39-6.65, 6.78-7.51 and 8.25-8.45 [all 12H, m, 6.55 (s), J=8.32 Hz)]

[0821] The compound of Example 180 1H-NMR (200 MHz, CDCl3) δ ppm: 1.15-4.65 and 5.05-5.21 [all 18H, m, 2.51 (s), 3.84 (s), 3.88 (s)], 6.40-7.42 [all 10H, m, 6.60 (d, J=7.62 Hz)]

[0822] The compound of Example 181 1H-NMR (200 MHz, CDCl3) δ ppm: 1.14-4.36, 4.45-4.83 and 5.0-5.25 [all 18H, m, 2.56 (s), 3.71 (s), 3.81 (s)], 6.43-7.78 [all 11H, m, 6.68 (d, J=7.67 Hz)]

[0823] The compound of Example 182 1H-NMR (200 MHz, CDCl3) δ ppm: 1.20-2.30, 2.45-3.94 and 4.44-4.65 [all 12H, m, 2.52 (s), 3.72 (s)], 6.42-6.77 (1H, m), 6.80-7.55 (6H, m), 8.35-8.75 (2H, m)

[0824] The compound of Example 183 1H-NMR (200 MHz, CDCl3) δ ppm: 1.19-4.01, 4.42-4.69 and 5.0-5.21 [all 15H, m, 2.55 (s), 3.81 (s)], 7.49-7.60 (all 11H, m)

[0825] The compound of Example 184 1H-NMR (200 MHz, CDCl3) δ ppm: 1.06-4.05, 4.39-4.65 and 4.99-5.20 [all 15H, m, 2.50 (s), 3.80 (s)], 6.35-7.52 [all 10H, m, 6.72 (d, J=7.32 Hz)]

[0826] The compound of Example 185 1H-NMR (200 MHz, CDCl3) δ ppm: 1.18-3.65, 3.92-4.30 and 4.80-5.10 [all 13H, m, 2.43 (s), 4.10 (s)], 6.46-7.58 and 8.01-8.49 [all 7H, m, 6.62 (d, J=5.48 Hz), 6.74 (d, J=6.66 Hz)]

[0827] The compound of Example 186 1H-NMR (200 MHz, CDCl3) δ ppm: 1.11-4.78 and 5.02-5.20 [all 14H, m, 2.44 (s), 4.62 (s)], 6.44-7.15 and 8.19-8.51 [all 12H, m, 6.55 (d, J=8.36 Hz)]

[0828] The compound of Example 187 1H-NMR (200 MHz, CDCl3) δ ppm: 1.19-2.30, 2.52-3.31, 3.42-4.78 and 5.09-5.28 [all 17H, m, 3.74 (s), 3.91 (s), 4.61 (s)], 6.42-7.58 and 8.85-9.10 [all 12H, m, 5.80 (d, J=8.36 Hz)]

[0829] The compound of Example 188 1H-NMR (200 MHz, CDCl3) δ ppm: 1.19-4.80 and 5.09-5.18 [all 14H, m, 3.88 (s), 4.59 (s)], 5.72-7.60 and 8.87-9.12 [all 13H, m, 6.56 (d, J=8.4 Hz)]

[0830] The compound of Example 189 1H-NMR (200 MHz, CDCl3) δ ppm: 1.08-4.23, 4.38-4.68 and 5.03-5.19 [all 17H, m, 3.74 (s), 3.79 (s), 4.54 (s)], 6.31-7.80 and 8.10-8.71 (all 12H, m)

[0831] The compound of Example 190 1H-NMR (200 MHz, CDCl3) δ ppm: 1.18-3.29, 3.41-4.69 and 5.07-5.27 [all 17H, m, 2.34 (s), 3.74 (s), 4.57 (s)], 6.43-7.71 and 8.21-8.50 [all 12H, m, 6.58 (d, J=6.36Hz), 6.85 (d, J=8.21 Hz)]

[0832] The compound of Example 192 1H-NMR (200 MHz, CDCl3) δ ppm: 1.09-3.85, 4.01-4.71 and 5.01-5.20 [all 17H, m, 2.46 (s), 3.74 (s), 4.64 (s)], 6.31-7.65 and 8.05-8.41 [all 13H, m, 6.55 (d, J=8.34 Hz)]

[0833] The compound of Example 193 1H-NMR (200 MHz, CDCl3) δ ppm: 1.18-4.73 and 5.03-5.26 [all 11H, m, 4.57 (s)], 6.49-7.52 and 8.20-8.41 [all 13H, m, 6.55 (d, J=8.39 Hz)]

[0834] The compound of Example 194 1H-NMR (200 MHz, CDCl3) δ ppm: 1.19-3.90, 4.28-4.72 and 5.09-5.26 [all 14H, m, 2.28 (s), 4.51 (s)], 5.60-7.50 and 8.20-8.45 [all 13H, m, 6.55 (d, J=8.58 Hz)]

[0835] The compound of Example 195 1H-NMR (200 MHz, CDCl3) δ ppm: 1.12-4.65 and 5.03-5.26 [all 14H, m, 2.33 (s), 4.54 (s)], 6.40-7.51and 8.21-8.43 [all 12H, m, 6.55 (d, J=8.06 Hz)]

[0836] The compound of Example 196 1H-NMR (200 MHz, CDCl3) δ ppm: 1.19-2.31, 2.49-4.65 and 5.08-5.26 [all 14H, m, 3.74 (s), 4.57 (s)], 6.45-6.67, 6.80-7.68 and 7.92-8.43 [all 13H, m, 6.57 (d, J=8.22 Hz)]

[0837] The compound of Example 197 1H-NMR (200 MHz, CDCl3) δ ppm: 1.11-2.22 and 2.41-5.95 (all 9H, m), 5.14 (2H, s), 6.62-6.48 and 6.75-7.59 [all 13H, m, 6.52 (d, J=8.24 Hz), 7.34 (s)]

[0838] The compound of Example 198 1H-NMR (200 MHz, CDCl3) δ ppm: 1.13-4.70 and 5.03-5.25 [all 17H, m, 2.30 (s), 3.74 (s), 4.53 (s)], 6.41-7.65 and 7.91-8.43 [all 13H, m, 6.56 (d, J=8.41 Hz)]

[0839] The compound of Example 199 1H-NMR (200 MHz, CDCl3) δ ppm: 1.15-2.22, 2.48-3.29 and 3.41-4.80 [all 14H, m, 3.67 (s), 3.72 (s)], 5.16 (2H, s), 6.15-6.20, 6.40-6.68, 6.75-8.40 and 9.31-9.48 [all 13H, m, 6.55 (d, J=8.24 Hz), (7.36 (s)]

[0840] The compound of Example 201 1H-NMR (200 MHz, CDCl3) δ ppm: 1.35-2.25 and 2.70-3.25 (all 7.2H, m), 3.45 (2.5H, s), 3.52 (0.5H, s), 3.94 (1.7H, s), 4.03 (0.3H, s), 4.75-5.10 (0.8H, m), 6.75-7.95 (7.2H, m), 8.18 (0.7H, s), 8.40 (0.1H, s)

[0841] The compound of Example 202 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.10-5.0 (28H, m), 6.60-7.80 (11H, m), 10.0-10.5 (1H, m), 11.0-11.8 (1H, m)

[0842] The compound of Example 203 1H-NMR (200 MHz, CDCl3) δ ppm: 1.35-2.25, 2.60-3.15 and 4.85-5.05 (all 8H, m), 2.45 and 2.49 (all 3H, each s), 2.95 and 2.97 (all 6H, each s), 4.53 and 4.65 (all 2H, each s), 6.26-7.55 (11.3H, m), 8.17 (0.7H, s)

[0843] The compound of Example 205 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.20-3.80 and 4.30-4.60 [all 23H, m, 2.34 (s), 2.37 (s)], 4.63 and 4.73 (all 2H, each s), 6.40-7.80 (12H, m), 10.1 and 10.35 (all 1H, each s), 10.7-11.4 (1H, m)

[0844] The compound of Example 206 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.10-4.90 [all 28H, m, 4.64 (s), 4.66 (s), 4.77 (s), 4.86 (s)], 6.65-8.05 (12H, m), 10.4-11.5 (2H, m)

[0845] The compound of Example 207 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.20-2.10 and 2.70-4.90 [all 25H, m, 3.70 (s)], 1.87 (3H, s), 6.50-7.70 (11H, m), 10.1-11.4 (2H, m)

[0846] The compound of Example 208 1H-NMR (250 MHz, CDCl3) δ ppm: 1.20-2.20, 2.20-3.20, 3.20-4.0 and 4.30-4.50 [all 25H, m, 2.29 (s)], 5.70-6.10, 6.51-7.40 and 7.40-8.00 (all 13H, m)

[0847] The compound of Example 209 1H-NMR (200 MHz, CDCl3) δ ppm: 1.35-2.15, 2.70-3.10 and 4.80-5.00 (all 10H, m), 3.66 and 3.76 [all 2H,each t, J=5.8 Hz], 4.60 and 4.71 [all 2H, each s], 6.70-7.050 (12H, m)

[0848] The compound of Example 210 1H-NMR (200 MHz, CDCl3) δ ppm: 1.20-2.30, 2.70-3.20 and 4.40-5.20 (all 10H, m), 6.25-8.10 (13H, m)

[0849] The compound of Example 211 1H-NMR (200 MHz, CDCl3) δ ppm: 1.35-2.20, 2.70-3.15, 3.20-3.60, 3.90-4.25 and 4.85-5.05 (all 13H, m), 6.21 (0.6H, dd, J=8.4Hz, J=2.2 Hz), 6.50 (0.7H, d, J=1.8Hz), 6.70 (0.9H, d, J=8.4 Hz), 6.80-7.40 (9.8H, m)

[0850] The compound of Example 214 1H-NMR (250 MHz, CDCl3) δ ppm: 1.20-4.60 [all 20H, m, 2.33 (s)], 5.15 and 5.21 (all 2H, each s), 6.70-8.10 (12H, m)

[0851] The compound of Example 220 1H-NMR (200 MHz, CDCl3) δ ppm: 1.35-1.75 (1H, m), 1.85-2.25 (3H, m), 2.75-3.25 (3H, m), 4.58 (2H, d, J=5.6 Hz), 4.9-5.1 (1H, m), 6.3-6.5 (1H, m), 6.58 (1H, d, J=7.4 Hz), 6.87 (1H, t, J=7.6 Hz), 7.06 (1 H, t, J=7.3 Hz), 7.19-7.32 (8H, m), 7.55 (2H, d, J=8.3 Hz)

[0852] The compound of Example 228 1H-NMR (200 MHz, CDCl3) δ ppm: 1.20-2.20, 2.30-3.35, 3.60-3.90 and 4.40-4.70 [all 14H, m, 2.45 (s), 4.48 (s)], 6.45-7.60 (12H, m), 8.28 and 8.49 (all 1H, each s)

[0853] The compound of Example 229 1H-NMR (200 MHz, CDCl3) δ ppm: 1.30-2.30, 2.70-3.90 and 4.40-4.60 (all 9H, m), 4.62 and 4.64 (all 2H, each s), 6.80-7.65 (12.5H, m), 8.48 and 8.75 (all 0.5H, each s)

[0854] The compound of Example 230 1H-NMR (200 MHz, CDCl3) δ ppm: 1.30-2.20, 2.70-3.10, 3.20-4.00 and 4.90-5.10 (all 10H, m), 2.44 and 2.48 (all 3H, each s), 4.48 and 4.57 (all 2H, each s), 6.20-7.35 (11H, m), 8.12 and 8.30 (all 1H, each s)

[0855] The compound of Example 231 1H-NMR (200 MHz, CDCl3) δ ppm: 1.20-2.20, 2.65-3.85 and 4.40-4.65 (all 9H, m), 2.42 (3H, s), 3.72 and 3.77 (all 3H, each s), 4.43 and 4.57 (all 2H, each s), 6.40-8.10 (12.2H, m), 8.36 and 8.64 (all 0.8H, each s)

[0856] The compound of Example 232 1H-NMR (200 MHz, CDCl3) δ ppm: 1.2-2.2, 2.2-3.35, 3.65-3.75 and 4.40-4.65 (all 9H, m), 2.29 and 2.33 (all 3H, each s), 2.42 (3H, s), 4.44 and 4.57 (all 2H, each s), 6.60-7.60 (13.5H, m), 8.36 and 8.62 (all 0.5H, each s)

[0857] The compound of Example 233 1H-NMR (250 MHz, DMSO-d6) δ ppm: 1.20-2.20, 2.60-3.65 and 4.20-4.40 (all 9H, m), 2.31 (3H, s), 5.10-5.16 (all 2H, each s), 6.46 (0.1H, d, J=8.3 Hz), 6.65 (0.9H, d, J=8.3 Hz), 6.82 (0.9H, d, J=8.4 Hz), 6.98-7.50 (9.4H, m), 9.72, 9.76 and 9.90 (all 0.7H, each s)

[0858] The compound of Example 234 1H-NMR (250 MHz, DMSO-d6) δ ppm: 1.20-1.65,1.80-2.10, 2.65-3.80 and 4.20-4.40 (all 9H, m), 5.11 and 5.18 (all 2H, each s), 6.70-7.80 (11.3H, m), 10.0 and 10.2 (all 0.7H, each s)

[0859] The compound of Example 235 1H-NMR (250 MHz, CDCl3) δ ppm: 1.20-3.85 and 4.05-4.50 [all 14H, m, 2.18 (s)], 5.50-7.60 (13.2H, m), 7.97 and 8.32 (all 0.8H, each s)

[0860] The compound of Example 237 1H-NMR (200 MHz, CDCl3) δ ppm: 0.82-4.26, 4.29-4.62 and 4.97-5.22 (all 31H, m), 6.42-8.18 (7H, m)

[0861] The compound of Example 238 1H-NMR (200 MHz, CDCl3) δ ppm: 1.08-5.25 (31H, m), 6.16-7.80 (9H, m), 12.08-13.75 (1H, m)

[0862] The compound of Example 239 1H-NMR (200 MHz, CDCl3) δ ppm: 0.91-4.02, 4.43-4.68 and 5.04-5.23 (all 22H, m), 2.31 (3H, s), 6.50-7.74 (11H, m)

[0863] The compound of Example 240 1H-NMR (200 MHz, CDCl3) δ ppm: 1.51-4.75 [all 28H, m, 2.31 (s), 3.90 (s)],6.46-7.63 (10H, m), 12.01-12.51 (1H, m)

[0864] The compound of Example 241 1H-NMR (200 MHz, CDCl3) δ ppm: 0.90-5.24 (22H, m), 6.51-7.72 (12H, m)

[0865] The compound of Example 242 1H-NMR (200 MHz, CDCl3) δ ppm: 1.17-2.55 (10H, m), 2.64-4.91 [all 18H, m, 3.86 (s), 3.90 (s)], 6.79-7.63 (10H, m), 12.42-12.83 (1H, m)

[0866] The compound of Example 243 1H-NMR (200 MHz, CDCl3) δ ppm: 1.49-2.68 (4H, m), 2.15 (3H, s), 2.69-3.04 and 4.44-5.21 (all 2H, m), 3.66, 3.76, 3.80 and 3.90 (all 6H, each s), 4.04-4.43 (2H, m), 6.54-7.62 (10H, m)

[0867] The compound of Example 244 1H-NMR (200 MHz, CDCl3) δ ppm: 1.45-2.62 [all 7H, m, 2.13 (s)], 2.71-3.06 and 3.07-5.19 [all 8H, m, 3.65 (s)], 6.00-7.65 (11H, m)

[0868] The compound of Example 245 1H-NMR (200 MHz, CDCl3) δ ppm: 1.00-5.22 (25H, m), 6.45-7.82 (11H, m, 12.52-13.54 (1H, m)

[0869] The compound of Example 246 1H-NMR (200 MHz, CDCl3) δ ppm: 1.14-2.55, 2.56-4.42 and 4.51-4.95 [all 25H, m, 3.95 (s)], 6.76-7.80 (11H, m), 12.40-12.98 (1H, m)

[0870] The compound of Example 247 1H-NMR (200 MHz, CDCl3) δ ppm: 1.21-5.12 [all 28H, m, 2.15 (s), 2.30 (s)], 6.52-7.72 (10H, m), 12.08-13.78 (1H, m)

[0871] The compound of Example 248 1H-NMR (200 MHz, CDCl3) δ ppm: 1.10-5.28 (22H, m), 2.36, 3.45 and 3.52 (each 3H, each s), 6.37-7.82 (9H, m), 12.34-13.35 (1H, m)

[0872] The compound of Example 250 1H-NMR (200 MHz, CDCl3) δ ppm: 1.14-4.29 and 4.42-4.68 [all 29H, m, 2.14 (s), 2.30 (s)], 6.47-7.62 (10H, m), 8.49-8.74 (1H, m), 11.17-12.00 (1H, m)

[0873] The compound of Example 251 1H-NMR (200 MHz, CDCl3) δ ppm: 1.10-4.22, 4.48-4.73 and 4.92-5.19 [all 32H, m, 3.74 (s), 3.85 (s), 3.93 (s)], 6.70-7.50 (10H, m), 11.62-12.22 (1H, m)

[0874] The compound of Example 252 1H-NMR (200 MHz, CDCl3) δ ppm: 1.09-2.51, 2.62-4.29 and 4.47-4.88 [all 28H, m, 2.43 (s), 3.94 (s)], 6.69-7.60 (10H, m), 12.06-13.01 (1H, m)

[0875] The compound of Example 253 1H-NMR (200 MHz, CDCl3) δ ppm: 1.08-4.22, 4.50-4.75 and 4.91-5.10 [all 32H, m, 2.37 (s), 2.42 (s), 3.77 (s)], 6.70-7.60 (10H, m), 11.60-12.50 (1H, m)

[0876] The compound of Example 254 1H-NMR (200 MHz, CDCl3) δ ppm: 1.05-2.62 and 2.63-5.19 [all 32H, m, 2.15 (s), 3.91 (s)], 6.51-7.68 (10H, m), 12.00-12.39 (1H, m)

[0877] The compound of Example 255 1H-NMR (200 MHz, CDCl3) δ ppm: 0.64-4.16 and 4.44-4.68 [all 20H, m, 0.73 (t, J=7.26 Hz), 2.29 (s), 2.55 (s)], 5.60-5.85 and 6.48-7.50 (all 11H, m)

[0878] The compound of Example 260 1H-NMR (200 MHz, CDCl3) δ ppm: 0.62-1.40, 1.41-2.19, 2.20-4.13 and 4.39-4.69 [all 17H, m, 0.73 (t, J=7.25 Hz), 2.57 (s)], 5.60-5.89 and 6.31-7.73 (all 12H, m)

[0879] The compound of Example 262 1H-NMR (200 MHz, CDCl3) δ ppm: 1.38-1.82, 1.83-2.35, 2.40-2.58, 2.65-3.78 and 4.82-5.15 [all 14H, m, 2.12 (s), 2.45 (s)], 6.60 (1H, d, J=8.36 Hz), 6.68-6.90 and 6.97-7.48 (all 9H, m)

[0880] The compound of Example 263 1H-NMR (200 MHz, CDCl3) δ ppm: 1.19-2.24, 2.37-2.60, 2.64-3.92 and 4.81-5.15 [all 11H, m, 2.48 (s)], 6.61 (1H, d, J=8.38 Hz), 6.71-6.92 and 7.02-7.68 (all 10H, m)

[0881] The compound of Example 264 1H-NMR (200 MHz, CDCl3) δ ppm: 1.16-4.38, 4.45-4.68 and 4.95-5.18 [all 32H, m, 1.32 (t), 2.12 (s), 2.29 (s), 2.50 (s), 3.30 (s)], 6.40-7.68 (10H, m), 11.48-12.38 (1H, m)

[0882] The compound of Example 265 1H-NMR (200 MHz, CDCl3) δ ppm: 0.74-4.08 and 4.42-4.69 [all 18H, m, 2.29 (s), 2.54 (s)], 5.59-5.80 and 6.29-7.51 (all 11H, m)

[0883] The compound of Example 266 1H-NMR (200 MHz, CDCl3) δ ppm: 0.75-4.05, 4.40-4.66, 4.76-5.09, 5.36-5.81 and 6.30-7.68 [all 25H, m, 2.57 (s), 4.96 (brs)], 6.45 (brs)]

[0884] The compound of Example 267 1H-NMR (200 MHz, CDCl3) δ ppm: 0.76-2.60 and 2.61-4.92 [all 31H, m, 2.08 (s), 3.85 (s)], 6.30-7.50 (9H, m), 12.22-12.86 (1H, m)

[0885] The compound of Example 268 1H-NMR (200 MHz, CDCl3) δ ppm: 0.73-2.56 and 2.57-4.94 [all 31H, m, 2.28 (s), 2.39 (s), 3.87 (s)], 6.52-7.52 (9H, m), 12.17-13.00 (1H, m)

[0886] The compound of Example 269 1H-NMR (200 MHz, CDCl3) δ ppm: 1.14-4.08, 4.41-4.68, 4.82-5.09, 5.37-5.96 and 6.30-7.58 [all 27H, m, 2.29 (s), 2.54 (s), 5.00 (brs), 6.45 (brs)]

[0887] The compound of Example 270 1H-NMR (200 MHz, CDCl3) δ ppm: 1.10-4.29, 4.41-4.68 and 4.96-5.15 [all 29H, m, 2.53 (s), 3.31 (s)], 6.38-7.72 (11H, m), 11.64-12.47 (1H, m)

[0888] The compound of Example 271 1H-NMR (200 MHz, CDCl3) δ ppm: 0.80-4.98 [23H, m, 2.52 (s), 2.58 (d, J=4.4 Hz)], 6.47-7.72 (11H, m), 12.56-13.30 (1H, m)

[0889] The compound of Example 272 1H-NMR (200 MHz, CDCl3) δ ppm: 0.58-4.00, 4.12-4.68 and 5.06-5.24 [all 14H, m, 1.63 (s)], 5.45-5.82 and 6.49-8.09 (all 17H, m)

[0890] The compound of Example 273 1H-NMR (200 MHz, CDCl3) δ ppm: 1.08-5.20 [all 20H, m, 2.85 (s)], 6.48-6.72, 6.81-7.08 and 7.09-7.79 [all 16H, m, 6.74 (d, J=8.2 Hz)], 12.62-13.78 (1H, m)

[0891] The compound of Example 274 1H-NMR (250 MHz, CDCl3) δ ppm: 1.04-5.24 (22H, m), 6.38-6.71 and 6.72-7.60 (all 16H, m), 12.49-13.31 (1H, m)

[0892] The compound of Example 275 1H-NMR (250 MHz, CDCl3) δ ppm: 1.10-5.19 [20H, m, 1.74 (s)], 6.41-6.68 and 6.79-7.60 (all 16H, m)

[0893] The compound of Example 276 1H-NMR (200 MHz, CDCl3) δ ppm: 0.78-2.34, 2.35-4.48, 4.49-4.74 and 4.92-5.12 [all 35H, m, 1.39 (t, d, J=7.0 Hz), 1.83 (s), 3.90 (s), 3.93 (s), 3.95 (s) 3.98 (s)], 6.70-7.60 (9H, m), 11.61-12.24 (1H, m)

[0894] The compound of Example 277 1H-NMR (200 MHz, CDCl3) δ ppm: 0.75-2.28, 2.29-4.33, 4.50-4.76 and 4.91-5.13 [all 32H, m, 1.85 (s), 2.39 (s), 2.45 (s), 3.30 (s), 3.77 (s), 3.99 (s)], 6.70-7.58 (10H, m), 11.58-12.27 (1H, m)

[0895] The compound of Example 278 1H-NMR (200 MHz, CDCl3) δ ppm: 1.12-4.29 and 4.42-4.93 [all 26H, m, 1.41 (t, J=7.3 Hz), 2.53 (s), 3.87 (s) ], 6.58-7.68 (11H, m), 12.52-13.50 (1H, m)

[0896] The compound of Example 279 1H-NMR (200 MHz, CDCl3) δ ppm: 0.48-1.41, 1.49-2.88, 2.94-3.28, 3.32-4.80 and 5.31-5.62 [all 22H, m, 0.52 (d, J=6.5 Hz), 0.96 (d, J=6.5 Hz), 2.58 (s), 3.87 (s)], 6.37-6.79 and 6.80-7.75 (all 12H, m)

[0897] The compound of Example 283 1H-NMR (250 MHz, CDCl3) δ ppm: 1.10-2.96, 2.97-3.91, 4.05-4.61 and 5.05-5.19 [all 20H, m, 1.63 (s), 2.87 (d, J=4.5 Hz)], 5.49-5.78, 6.07-6.32, 6.46-6.69 and 6.81-7.62 (all 9H, m)

[0898] The compound of Example 284 1H-NMR (250 MHz, CDCl3) δ ppm: 0.79-4.32, 4.33-4.66 and 4.99-5.26 [all 34H, m, 1.41 (t, J=5.8 Hz), 3.31 (s)], 6.02-6.37, 6.45-6.68 and 6.78-7.81 (all 8H, m), 11.83-12.39 (1H, m)

[0899] The compound of Example 285 1H-NMR (250 MHz, CDCl3) δ ppm: 1.17-3.40, 3.52-4.10, 4.11-4.62 and 5.04-5.23 [all 36H, m, 1.41 (t, J=7.18 Hz), 3.31 (s)], 6.05 (1H, t, J=6.68 Hz), 6.51-6.69 and 6.82-7.68 (7H, m), 11.99-12.39 (1H, m)

[0900] The compound of Example 286 1H-NMR (200 MHz, CDCl3) δ ppm: 0.35-0.65, 0.80-2.12, 2.13-2.88, 2.89-3.23, 3.32-4.24, 4.34-4.65, 5.26-5.47 and 6.31-7.44 [all 38H, m, 0.50 (d, J=6.5 Hz), 0.94 (d, J=6.5 Hz), 2.49 (s)]

[0901] The compound of Example 287 1H-NMR (200 MHz, CDCl3) δ ppm: 0.50-0.81, 1.00-2.13, 2.14-3.17, 3.21-4.00, 4.36-4.62, 5.48-5.71 and 6.39-7.43 [all 38H, m, 0.65 (t, J=7.3 Hz), 2.49 (s)]

[0902] The compound of Example 288 1H-NMR (200 MHz, CDCl3) δ ppm: 0.81-2.55 (5H, m), 2.31 (3H, s), 2.56-3.97 4.31-4.70 and 5.08-5.50 (all 4H, m), 6.50-7.83 (12H, m)

[0903] The compound of Example 289 1H-NMR (200 MHz, CDCl3) δ ppm: 1.15-2.49 [all 8H, m, 1.95 (s)], 2.59-3.94, 4.00-4.25, 4.40-4.67 and 5.09-5.29 [all 13H, m, 3.47 (s), 3.55 (s), 3.68 (s)], 6.30-7.48 (9H, m)

[0904] The compound of Example 291 1H-NMR (200 MHz, CDCl3) δ ppm: 1.15-2.27 (5H, m), 2.52-4.33, 4.51-4.73 and 5.00-5.19 [all 13H, m, 3.70 (s), 3.74 (s), 3.75 (s)], 6.71-7.54 (10H, m)

[0905] The compound of Example 292 1H-NMR (200 MHz, CDCl3) δ ppm: 1.27-2.42 (5H, m), 2.36 (3H, s), 2.58-3.07 (2H, m), 3.10-4.31, 4.38-4.67 and 5.19-5.29 [all 11H, m, 3.53 (s), 3.68 (s)], 6.41-7.48 (9H, m)

[0906] The compound of Example 293 1H-NMR (200 MHz, CDCl3) δ ppm: 1.09-2.42 (5H, m), 2.58-4.24, 4.49-4.74 and 5.01-5.22 (all 10H, m), 5.24-7.56 (11H, m)

[0907] The compound of Example 294 1H-NMR (200 MHz, CDCl3) δ ppm: 1.18-2.58 (4H, m), 2.35 (3H, s), 2.60-4.09, 4.36-4.68 and 5.02-5.30 (all 5H, m), 3.49 (6H, s), 6.31-7.49 (10H, m)

[0908] The compound of Example 295 1H-NMR (200 MHz, CDCl3) δ ppm: 1.16-2.47 (4H, m), 2.58-3.40, 3.41-4.38, 4.39-4.68 and 5.09-5.30 (all 11H, m), 3.67 and 3.71 (each 3H, each s), 6.55-7.83 (11H, m)

[0909] The compound of Example 296 1H-NMR (200 MHz, CDCl3) δ ppm: 1.19-2.39 (4H, m), 2.51-3.95, 4.36-4.64 and 5.05-5.31 [all 8H, m, 3.65 (s)], 6.50-7.80 (11H, m), 8.99-10.36 (1H, m)

[0910] The compound of Example 297 1H-NMR (200 MHz, CDCl3) δ ppm: 1.18-2.34, 2.58-3.30, 3.31-4.37, 4.51-4.72 and 5.01-5.19 [all 15H, m, 3.76 (s)], 6.71-7.69 (11H, m)

[0911] The compound of Example 298 1H-NMR (200 MHz, CDCl3) δ ppm: 1.15-2.29 (4H, m), 2.57-3.21, 3.30-4.13, 4.49-4.72 and 4.99-5.21 [all 8H, m, 3.73 (s)], 5.41-7.69 (12H, m)

[0912] The compound of Example 299 1H-NMR (200 MHz, CDCl3) δ ppm: 1.12-2.22, 2.24-2.52, 2.57-3.19, 3.28-4.41, 4.51-4.73 and 4.99-5.20 [all 18H, m, 2.37 (s), 3.76 (s)], 6.71-7.58 (10H, m)

[0913] The compound of Example 300 1H-NMR (200 MHz, CDCl3) δ ppm: 1.07-4.14 and 4.15-5.58 [all 16H, m, 2.35 (s), 3.73 (s)], 6.62-7.64 (10H, m)

[0914] The compound of Example 301 1H-NMR (200 MHz, CDCl3) δ ppm: 1.13-2.31 [all 10H, m, 1.90 (s)], 2.54-3.23, 3.33-3.97, 4.05-4.31, 4.51-4.71 and 5.01-5.18 [all 11H, m, 3.74 (s)], 6.31-7.50 (9H, m)

[0915] The compound of Example 302 1H-NMR (200 MHz, CDCl3) δ ppm: 1.14-2.22 (4H, m), 2.57-3.20, 3.36-4.35, 4.50-4.71 and 5.02-5.20 [all 17H, m, 3.76 (s), 3.91 (s), 3.93 (s)], 6.71-7.55 (9H, m)

[0916] The compound of Example 303 1H-NMR (200 MHz, CDCl3) δ ppm: 1.11-2.51 [all 7H, m, 2.39 (s)], 2.57-3.21, 3.22-4.35, 4.51-4.73 and 5.01-5.19 [all 11H, m, 3.76 (s)], 6.70-7.55 (10H, m)

[0917] The compound of Example 304 1H-NMR (200 MHz, CDCl3) δ ppm: 1.15-2.49 [all 10H, m, 2.11 (s), 2.34 (s)], 2.56-3.22, 3.30-4.32, 4.49-4.73 and 5.02-5.19 [all 11H, m, 3.67 (s), 3.74 (s)], 6.48-7.52 (9H, m)

[0918] The compound of Example 307 1H-NMR (200 MHz, CDCl3) δ ppm: 1.09-2.25 (4H, m), 2.37 and 2.44 (all 3H, each s), 2.55-3.30, 3.31-4.22 and 4.49-6.21 [all 9H, m, 3.73 (s)], 6.70-7.58 (10H, m)

[0919] The compound of Example 309 1H-NMR (200 MHz, CDCl3) δ ppm: 1.14-4.23, 4.42-4.69 and 5.03-5.25 [all 18H, m, 2.13 (s), 2.48 (s), 3.71 (s)], 6.30-7.54 (10H, m)

[0920] The compound of Example 310 1H-NMR (200 MHz, CDCl3) δ ppm: 1.17-2.29 (4H, m), 2.39-4.32, 4.43-4.65 and 5.02-5.22 [all 11H, m, 2.51 (s), 3.74 (s)], 6.41-7.69 (11H, m)

[0921] The compound of Example 311 1H-NMR (200 MHz, CDCl3) δ ppm: 1.05-3.99, 4.38-4.65 and 5.01-5.22 [all 15H, m, 2.12 (s), 2.47 (s)], 6.40-7.48 (10H, m)

[0922] The compound of Example 312 1H-NMR (200 MHz, CDCl3) δ ppm: 1.12-2.34 (4H, m), 2.35-4.09, 4.40-4.68 and 5.03-5.25 [all 8H, m, 2.50 (s)], 6.40-7.70 (11H, m)

[0923] The compound of Example 313 1H-NMR (200 MHz, CDCl3) δ ppm: 1.19-2.52, 2.53-3.94, 3.97-4.32, 4.37-4.62 and 5.07-5.28 [all 20H, m, 3.74 (s)], 6.00-6.32, 6.40-6.68, 6.70-7.01 and 7.02-7.40 (all 8H, m)

[0924] The compound of Example 314 1H-NMR (250 MHz, CDCl3) δ ppm: 1.08-2.37, 2.38-3.92, 4.01-4.64 and 5.08-5.28 [all 22H, m, 3.74 (s)], 6.07 (1H, t, J=6.7 Hz), 6.41-6.71 and 6.72-7.41 (all 7H, m)

[0925] The compound of Example 315 1H-NMR (250 MHz, CDCl3) δ ppm: 1.12-2.31, 2.48-3.32, 3.37-3.82, 3.83-4.36, 4.37-4.58 and 5.10-5.25 [all 12H, m, 1.58 (s), 3.59 (s)], 6.43-6.66 and 6.79-7.52 (all 16H, m)

[0926] The compound of Example 316 1H-NMR (250 MHz, CDCl3) δ ppm: 1.22-3.06, 3.07-3.25, 3.32-3.79, 4.38-4.60 and 5.08-5.24 [all 9H, m, 3.48 (s), 3.58 (s)], 6.42-6.63 and 6.78-8.51 (all 17H, m)

[0927] The compound of Example 317 1H-NMR (250 MHz, CDCl3) δ ppm: 1.12-2.52, 2.53-3.33, 3.34-3.88, 3.89-4.65, and 5.08-5.25 (all 17H, m), 5.99-6.36, 6.44-6.70 and 6.78-7.55 (all 9H, m)

[0928] The compound of Example 318 1H-NMR (250 MHz, CDCl3) δ ppm: 1.16-3.32, 3.33-4.62 and 5.08-5.26 (all 19H, m), 6.05 (1H, t, J=6.7 Hz), 6.48-6.74 and 6.75-7.81 (all 8H, m)

[0929] The compound of Example 319 1H-NMR (250 MHz, CDCl3) δ ppm: 1.19-2.30, 2.57-3.90, 3.91-4.67 and 5.21-5.31 [all 12H, m, 1.59 (s)], 6.49-6.74 and 6.81-7.87 (all 16H, m)

[0930] The compound of Example 320 1H-NMR (250 MHz, CDCl3) δ ppm: 1.18-2.26 (4H, m), 2.55-3.36, 3.37-3.90, 4.38-4.62 and 5.10-5.30 (all 5H, m), 6.50-6.71 and 6.82-7.81 (all 17H, m)

[0931] The compound of Example 321 1H-NMR (200 MHz, CDCl3) δ ppm: 1.18-2.39, 2.40-4.27, 4.46-4.68 and 5.06-5.22 [all 18H, m, 2.52 (s), 3.72 (s), 3.82 (s) and 3.87 (s)], 6.48-7.68 (11H, m)

[0932] The compound of Example 322 1H-NMR (200 MHz, CDCl3) δ ppm: 0.86-4.31, 4.43-4.67 and 5.03-5.20 [all 26H, m, 2.43 (s), 2.47 (s), 3.72 (s)], 6.41-7.46 (7H, m)

[0933] The compound of Example 323 1H-NMR (200 MHz, CDCl3) δ ppm: 1.07-4.31, 4.40-4.67 and 5.02-5.20 [all 28H, m, 2.43 (s), 2.47 (s), 3.72 (s)], 6.40-7.46 (7H, m)

[0934] The compound of Example 324 1H-NMR (200 MHz, CDCl3) δ ppm: 1.15-4.31, 4.43-4.65 and 5.02-5.20 [all 24H, m, 2.43 (s), 2.48 (s), 3.71 (s)], 6.44-7.48 (7H, m)

[0935] The compound of Example 325 1H-NMR (200 MHz, CDCl3) δ ppm: 0.98-5.26 [24H, m, 2.43 (s), 2.48 (s)], 6.42-7.53 [7H, m, 6.64 (d, J=7.3 Hz)]

[0936] The compound of Example 326 1H-NMR (200 MHz, CDCl3) δ ppm: 1.03-4.04, 4.42-4.64 and 5.01-5.21 [all 25H, m, 2.43 (s)], 6.41-7.45 (7H, m)

[0937] The compound of Example 327 1H-NMR (200 MHz, CDCl3) δ ppm: 1.04-4.01, 4.40-4.66 and 5.02-5.22 [all 21H, m, 2.43 (s), 2.48 (s)], 6.43-7.48 (7H, m)

[0938] The compound of Example 328 1H-NMR (200 MHz, CDCl3) δ ppm: 1.14-2.28, 2.38-4.02, 4.41-4.68 and 5.02-5.22 [all 15H, m, 2.51 (s), 2.56 (s), 3.78 (s)], 6.48-7.62 (11H, m)

[0939] The compound of Example 329 1H-NMR (200 MHz, CDCl3) δ ppm: 1.15-2.32 (4H, m), 2.43-4.32, 4.45-4.68 and 5.03-5.22 [all 11H, m, 2.55 (s), 2.58 (s), 3.73 (s)], 6.43-7.80 (16H, m)

[0940] The compound of Example 332 1H-NMR (200 MHz, CDCl3) δ ppm: 0.54-1.04, 1.05-2.25, 2.26-4.18, 4.36-4.74 and 5.52-5.84 [all 17H, m, 0.67 (t, J=7.3 Hz), 2.60 (s)], 6.38-7.82 (17H, m)

[0941] The compound of Example 333 1H-NMR (200 MHz, CDCl3) δ ppm: 0.9-4.2, 4.4-4.65 and 5.0-5.25 (all 22H, m), 6.45-6.67 and 6.78-7.88 [all 13H, m, 6.58 (d, J=8.3 Hz)]

[0942] The compound of Example 334 1H-NMR (200 MHz, CDCl3) δ ppm: 0.9-4.1, 4.45-4.65 and 5.0-5.2 [all 22H, m, 1.23 (t, J=7.1 Hz)], 6.35-7.55 (13H, m)

[0943] The compound of Example 335 1H-NMR (200 MHz, CDCl3) δ ppm: 1.06 (3H, t, J=7.2 Hz), 1.1-1.55 (5H, m), 1.6-2.0 (5H, m), 2.2-2.7 (9H, m), 3.4-3.9 (7H, m), 4.55-4.85 (1H, m), 6.19 (1H, t, J=5.5 Hz), 6.62 (1H, d, J=8.2 Hz), 6.8-7.1 (1H, m), 6.99 (2H, d, J=7.9 Hz), 7.16 (2H, d, J=7.9 Hz), 7.33 (1H, d, J=2.4 Hz)

[0944] The compound of Example 336 1H-NMR (200 MHz, CDCl3) δ ppm: 1.05 (3H, t, J=7.2 Hz), 2.2-2.7 (8H, m), 3.4-3.9 (7H, m), 4.6-4.9 (1H, m), 6.21 (1H, t, J=5.8 Hz), 6.65 (1H, d, J=8.3 Hz), 6.8-7.1 (1H, m), 7.2-7.6 (10H, m)

[0945] The compound of Example 337 1H-NMR (200 MHz, CDCl3) δ ppm: 0.99 and 1.21 (all 6H, each t, J=7 Hz), 2.0-2.8 (7H, m), 3.0-4.9 (7H, m), 6.34 (1H, t, J=5.5 Hz), 6.65 (1H, d, J=8.1 Hz), 6.75-7.8 (12H, m)

[0946] The compound of Example 339 1H-NMR (200 MHz, CDCl3) δ ppm: 1.2-4.2, 4.4-4.7 and 5.0-5.2 (all 19H, m), 6.5-6.7 [1H, m, 6.63 (d, J=7.1 Hz)], 6.8-7.8 (12H, m), 8.2-8.7 (1H, m)

[0947] The compound of Example 340 1H-NMR (200 MHz, CDCl3+DMSO-d6) δ ppm: 1.0-4.8 and 5.0-5.2 [all 24H, m, 1.47 (t, J=7.1 Hz)], 6.5-8.0 (13H, m), 8.9-9.8 (1H, m), 11.6-12.5 (1H, m)

[0948] The compound of Example 341 1H-NMR (200 MHz, CDCl3) δ ppm: 1.1-2.3,2.4-4.7 and 4.9-5.15 (all 21H, m), 6.58 (1H, d, J=7.7 Hz), 6.7-7.8 (12H, m), 8.35-8.8 (1H, m)

[0949] The compound of Example 342 1H-NMR (200 MHz, CDCl3) δ ppm: 0.9-4.0, 4.4-4.7 and 5.0-5.25 (all 21H, m), 6.5-6.7 (1H, m), 6.8-7.7 (12H, m), 8.2-8.5 (1H, m)

[0950] The compound of Example 344 1H-NMR (200 MHz, CDCl3) δ ppm: 0.9-4.1, 4.4-4.7 and 4.9-5.15 [all 27H, m, 1.12 (t, J=5.7 Hz), 2.49 (s), 4.52 (s)], 6.4-7.7 [12H, m, 6.62 (d, J=6.1 Hz)], 8.1-8.5 [1H, m, 8.15 (s), 8.41 (s)]

[0951] The compound of Example 345 1H-NMR (250 MHz, CDCl3) δ ppm: 0.9-4.1, 4.3-4.8 and 4.9-5.1 (all 24H, m), 6.7-8.0 (11H, m), 8.3-8.8 [1H, m, 8.38 (s), 8.67 (s)]

[0952] The compound of Example 346 1H-NMR (200 MHz, CDCl3) δ ppm: 1.0-5.1 [24H, m, 2.46 (s), 2.47 (s), 4.48 (s), 4.61 (s)], 6.35-6.7 [1H, m, 6.58 (d, J=5.5 Hz)], 6.75-8.0 (12H, m), 8.3-8.7 [1H, m, 8.42 (s), 8.59 (s)]

[0953] The compound of Example 350 1H-NMR (200 MHz, CDCl3) δ ppm: 1.2-4.2, 4.4-4.7 and 4.9-5.2 [all 23H, m, 2.35 (s), 2.53 (s)], 6.4-8.5 [12H, m, 6.58 (d, J=8.3 Hz), 6.87 (dd, J=8.3, J=2.3 Hz), 6.99 (d, J=2.2 Hz), 7.10 (d, J=8.3 Hz), 10.0-10.04 (1H, m)

[0954] The compound of Example 352 1H-NMR (200 MHz, CDCl3) δ ppm: 1.05-1.55 and 1.6-2.0 [all 13H, 1.25 (t, J=7 Hz)], 2.2-2.8 (3H, m), 3.2-3.55 (2H, m), 3.6-3.9 (1H, m), 4.0-4.4 (2H, m), 4.6-4.9 (1H, m), 6.29 (1H, t, J=5.6 Hz), 5.62 (1H, d, J=8 Hz), 6.89 (1H, dd, J=8 Hz, J=2 Hz), 6.99 (2H, d, J=8.2 Hz), 7.18 (2H, d, J=8.2 Hz), 7.35 (1H, d, J=2 Hz)

[0955] The compound of Example 353 1H-NMR (200 MHz, CDCl3) δ ppm: 1.1-2.0 (10H, m), 2.2-2.8 (3H, m), 3.2-3.6 (2H, m), 3.65-3.9 (1H, m), 4.6-4.95 (1H, m), 6.28 (1H, t, J=5.4 Hz), 6.61 (1H, d, J=8 Hz), 6.8-7.1 (1H, m), 6.98 (2H, d, J=8 Hz), 7.21 (2H, d, J=8 Hz), 7.35 (1H, d, J=2.3 Hz), 9.03 (1H, brs)

[0956] The compound of Example 354 1H-NMR (200 MHz, CDCl3) δ ppm: 2.15-2.8 (2H, m), 3.25-3.6 (2H, m), 3.65-3.95 (1H, m), 4.6-4.9 (1H, m), 6.25 (1H, t, J=5.6 Hz), 6.63 (1H, J=8.1 Hz), 6.8-7.0 (1H, m), 7.2-7.6 (10H, m), 9.1 (1H, br)

[0957] The compound of Example 355 1H-NMR (200 MHz, CDCl3) δ ppm: 1.1-2.2, 2.6-3.35, 3.4-3.95, 4.0-4.7 and 5.05-5.25 [all 14H, 3.72 (s)], 6.45-6.7 [1H, m, 6.63 (d, J=7.6 Hz)], 6.8-7.5 (12H, m), 8.15-8.4 (1H, m)

[0958] The compound of Example 356 1H-NMR (250 MHz, CDCl3) δ ppm: 1.2-4.9 and 5.0-5.25 [all 17H, m, 2.46 (s), 3.70 (s), 4.51 (s)], 6.4-7.6 [12H, m, 6.62 (d, J=8.1 Hz)], 8.1-8.6 (1H, m)

[0959] The compound of Example 357 1H-NMR (250 MHz, CDCl3) δ ppm: 1.1-2.2 (4H, m), 2.6-3.0 (2H, m), 3.1-3.3, 3.4-3.9, 4.4-4.7 and 4.9-5.2 [all 8H, m, 3.73 (s), 4.56 (s)], 6.8-8.0, 8.2-8.4 and 8.45-8.6 (all 12H, m)

[0960] The compound of Example 358 1H-NMR (250 MHz, CDCl3) δ ppm: 1.1-2.25 (4H, m), 2.5-5.2 (7H, m), 6.2-8.1 (11H, m), 8.3-8.8 [1H, m, 8.42 (s)]

[0961] The compound of Example 359 1H-NMR (200 MHz, CDCl3) δ ppm: 1.2-4.7 and 5.0-5.2 [all 15H, m, 2.48 (s), 3.74 (s)], 6.3-6.7 [1H, m, 6.57 (d, J=8.7 Hz)], 6.7-7.8 (10H, m), 8.3-8.8 [1H, m, 8.41 (s), 8.72 (s)]

[0962] The compound of Example 360 1H-NMR (200 MHz, CDCl3) δ ppm: 1.1-4.7 and 5.0-5.2 [all 15H, m, 2.49 (s), 3.68 (s)], 6.1-8.0 [10H, m, 6.60 (d, J=8.4 Hz)], 9.4-8.8 [1H, m, 9.54 (s), 9.75 (s)], 12.1-12.4 [1H, m, 12.27 (s)]

[0963] The compound of Example 361 1H-NMR (200 MHz, CDCl3) δ ppm: 1.1-3.9 and 4.3-5.3 [all 12H, m, 2.45 (s)], 6.3-6.7 [1H, m, 6.57 (d, J=8.4 Hz)], 6.7-7.8 (10H, m), 8.40 and 8.65 (all 1H, each s)

[0964] The compound of Example 362 1H-NMR (200 MHz, CDCl3) δ ppm: 1.1-3.9, 4.2-4.6 and 4.9-5.2 [all 12H, m, 2.43 (s)], 6.3-7.9 [11H, m, 6.57 (d, J=8.3 Hz)], 8.44 and 8.74 (all 1H, each s)

[0965] The compound of Example 363 1H-NMR (200 MHz, CDCl3) δ ppm: 1.7-2.4 (2H, m), 2.87 (2H, t, J=6 Hz), 3.4-5.2 [4H, m, 4.55 (s)], 6.8-8.1 (12H, m), 8.2-8.7 [1H, m, 8.35 (s)]

[0966] The compound of Example 365 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.1-5.1 [12H, m, 2.42 (s)], 6.4-8.8 [13H, m, 6.72 (d, J=8.4 Hz), 8.60 (d, J=8.3 Hz)], 10.5-10.9 (1H, m)

[0967] The compound of Example 366 1H-NMR (200 MHz, CDCl3) δ ppm: 0.95-4.05, 4.48-4.72 and 4.96-5.14 [all 27H, m, 1.06 (t, J=7.3 Hz), 2.38 (s)], 6.48-7.73 [12H, m, 6.68 (d, J=7.5 Hz)]

[0968] The compound of Example 367 1H-NMR (200 MHz, CDCl3) δ ppm: 1.05 (3H, t, J=7.3 Hz), 1.18-4.18, 4.42-4.72 and 4.97-5.15 [all 24H, m, 2.34 (s)], 6.40-6.68 and 6.73-7.74 [all 11H, m, 6.61 (d, J=8.3 Hz)]

[0969] The compound of Example 370 1H-NMR (200 MHz, CDCl3) δ ppm: 1.05 (3H, t, J=7.3 Hz), 1.20-2.32, 2.59-4.00, 4.43-4.72 and 5.03-5.21 (all 13H, m), 6.51-7.72 [all 12H, m, 6.69 (d, J=7.4 Hz)]

[0970] The compound of Example 371 1H-NMR (200 MHz, CDCl3) δ ppm: 1.05 (3H, t, J=7.3 Hz), 1.17-2.28, 2.55-3.90, 4.34-4.66 and 5.01-5.22 (all 13H, m), 6.43-7.69 [all 11H, m, 6.63 (d, J=8.3 Hz)]

[0971] The compound of Example 375 1H-NMR (200 MHz, CDCl3) δ ppm: 1.18-2.25 (4H, m), 2.60-3.15 (3H, m), 3.35-3.80 (1H, m), 4.50-5.20 (1H, m), 6.60-6.72 (1H, m), 6.90-7.00 (1H, m), 7.02 (1H, d, J=8.2 Hz), 7.16 (1H, dd, J=2.3 Hz, J=8.3 Hz), 7.21-7.54 (5H, m)

[0972] The compound of Example 377 1H-NMR (200 MHz, CDCl3) δ ppm: 1.13-2.28 (4H, m), 2.50-3.18 (3H, m), 3.31-3.60 (1H, m), 4.48-5.19 (1H, m), 7.02 (1H, dd, J=1.7 Hz, J=8.2 Hz), 7.06-7.52 (9H, m)

[0973] The compound of Example 379 1H-NMR (200 MHz, CDCl3) δ ppm: 1.17-2.30 (4H, m), 2.61-3.20 (2H, m), 3.20-3.45 (1H, m), 3.50-3.98 (1H, m), 4.42-5.33 (1H, m), 6.50-6.65 (1H, m), 6.72-7.56 (6H, m), 7.62 (1H, dd, J=2.0 Hz, J=8.8 Hz), 7.71 (1H, d, J=8.6 Hz), 7.78-8.08 (4H, m), 8.12 (1H, d, J=8.6 Hz)

[0974] The compound of Example 383 1H-NMR (200 MHz, CDCl3) δ ppm: 1.17-2.22 (7H, m), 2.69-3.93 (6H, m), 4.41-5.23 (1H, m), 6.45-7.73 (11H, m)

[0975] The compound of Example 385 1H-NMR (200 MHz, CDCl3) δ ppm: 1.15-2.28 (7H, m), 2.56-3.08 (4H, m), 3.08-3.96 (2H, m), 4.40-5.21 (1H, m), 6.40-7.16 (4H, m), 7.16-7.75 (8H, m)

[0976] The compound of Example 386 1H-NMR (200 MHz, CDCl3) δ ppm: 0.70-1.16 (6H, m), 1.20-3.66 (18H, m), 3.66-3.97 (1H, m), 4.48-5.19 (1H, m), 6.51-7.21 (2H, m), 7.21-8.10 (7H, m)

[0977] The compound of Example 387 1H-NMR (200 MHz, CDCl3) δ ppm: 0.80-1.18 (3H, m), 1.19-2.58 (10H, m), 2.58-3.21 (4H, m), 3.29-3.80 (4H, m), 4.52-5.11 (1H, m), 6.40-6.87 (1H, m), 6.90-7.11 (2H, m), 7.11-7.44 (4H, m), 7.44-7.68 (3H, m)

[0978] The compound of Example 388 1H-NMR (200 MHz, CDCl3) δ ppm: 0.85 (3H, t, J=7.1 Hz), 1.02 (3H, t, J=7.1 Hz), 1.15-2.28 (3H, m), 2.38 (4H, q, J=7.1 Hz), 2.56 (4H, q, J=7.1 Hz), 2.63-3.49 (4H, m), 3.50-3.79 (1H, m), 4.51-5.14 (1H, m), 5.65-6.79 (2H, m), 6.90-7.10 (2H, m), 7.10-7.21(1H, m), 7.10-7.62 (6H, m)

[0979] The compound of Example 389 1H-NMR (200 MHz, CDCl3) δ ppm: 0.82-1.19 (3H, m), 1.20-2.55 (10H, m), 2.55-3.19 (4H, m), 3.19-3.87 (4H, m), 4.55-5.13 (1H, m), 6.81-7.72 (10H, m)

[0980] The compound of Example 390 1H-NMR (250 MHz, CDCl3) δ ppm: 0.84 (3H, t, J=7.1 Hz), 1.00 (3H, t, J=7.2 Hz), 1.21-2.42 (8H, m), 2.42-2.68 (4H, m), 2.68-3.46 (3H, m), 3.52-3.81 (1H, m), 4.53-5.14 (1H, m), 5.65-6.51 (1H, m), 6.88-7.11 (2H, m), 7.11-7.22 (1H, m), 7.11-7.65 (8H, m)

[0981] The compound of Example 391 1H-NMR (250 MHz, CDCl3) δ ppm: 0.88-1.27 (3H, m), 1.30-2.89 (10H, m), 2.99-3.20 (1H, m), 3.20-4.12 (7H, m), 4.45-5.29 (1H, m), 6.48-6.67 (1H, m), 6.75-6.90 (1H, m), 7.02 (1H, d, J=2.1 Hz), 7.40-8.09 (7H, m), 8.09-8.20 (2H, m), 8.31 (1H, d, J=8.6 Hz)

[0982] The compound of Example 392 1H-NMR (250 MHz, CDCl3) δ ppm: 0.81-1.19 (6H, m), 1.25-2.30 (4H, m), 2.30-2.77 (7H, m), 2.77-5.30 (6H, m), 6.29-6.78 (2H, m), 6.81 (1H, dd, J=2.2 Hz, J=8.3 Hz), 7.11-7.38 (1H, m), 7.38-7.66 (3H, m), 7.66-7.89 (2H, m), 7.89-8.24 (4H, m), 8.31 (1H, d, J=8.6 Hz)

[0983] The compound of Example 393 1H-NMR (250 MHz, CDCl3) δ ppm: 0.78-2.30 (5H, m), 2.35 (3H, s), 2.41-2.60 (3H, m), 2.60-3.52 (3H, m), 3.52-4.01 (5H, m), 4.46-5.26 (1H, m), 6.50-6.09 (1H, m), 6.89 (1H, dd, J=2.2 Hz, J=8.3 Hz), 7.02 (1H, d, J=2.2 Hz), 7.09-7.20 (1H, m), 7.28-7.55 (1H, m), 7.60-7.90 (6H, m), 8.38 (1H, s)

[0984] The compound of Example 394 1H-NMR (250 MHz, CDCl3) δ ppm: 0.79-1.20 (6H, m), 1.29-2.82 (10H, m), 2.82-4.02 [9H, m, 3.00 (s), 3.22 (s)], 4.40-5.25 (1H, m), 6.50-6.68 (1H, m), 6.83-7.20 (3H, m), 7.25-7.52 (1H, m), 7.58-7.87 (6H, m), 8.37 (1H, d, J=5.2 Hz)

[0985] The compound of Example 397 1H-NMR (200 MHz, CDCl3) δ ppm: 1.20-4.18, 4.40-4.72 and 4.96-5.20 [all 25H, m, 2.35 (s), 2.88 (q, J=7.4 Hz)], 6.40-7.85 (11H, m)

[0986] The compound of Example 398 1H-NMR (200 MHz, CDCl3) δ ppm: 1.15-4.10, 4.49-4.75 and 4.98-5.18 [all 25H, m, 2.33 (s)], 6.45-7.72 (12H, m)

[0987] The compound of Example 404 1H-NMR (200 MHz, CDCl3) δ ppm: 1.18-2.28 (10H, m), 2.54-4.08 (15H, m), 4.18-5.22 (1H, m), 6.50-6.70 (2H, m), 6.72-6.90 (1H, m), 7.08-7.78 (9H, m) 12.02 (1H, brs)

[0988] The compound of Example 408 1H-NMR (200 MHz, CDCl3) δ ppm: 1.15-5.15 (17H, m), 2.86 (3H, s), 6.49-6.70 (2H, m), 6.72-6.90 (1H, m), 6.93-7.81 (9H, m), 12.27 (1H, brs)

[0989] The compound of Example 413 1H-NMR (200 MHz, CDCl3) δ ppm: 1.46-4.00, 4.27-4.80 and 5.03-5.17 (all 13H, m), 6.68 (1H, d, J=8.3 Hz), 6.80-7.69 (12H, m)

[0990] The compound of Example 415 1H-NMR (200 MHz, CDCl3) δ ppm: 1.35-4.15 and 4.80-5.10 (all 13H, m), 6.45-7.90 (12H, m)

[0991] The compound of Example 417 1H-NMR (200 MHz, CDCl3) δ ppm: 0.87 (3H, t, J=7.3 Hz), 1.35-2.22, 2.66-3.17 and 4.88-5.09 (all 10H, m), 4.08 (2H, t, J=7.3 Hz), 6.57 (1H, d, J=8.3 Hz), 6.89 (1H, dd, J=2 Hz, J=8.3 Hz), 7.15-7.49 (3H, m), 7.53-7.69 (2H, m), 11.39-11.64 (1H, brs)

[0992] The compound of Example 418 1H-NMR (200 MHz, CDCl3) δ ppm: 0.99-4.17 and 4.45-4.65 [all 25H, m, 1.84 (s)], 6.56-6.65, 6.82-7.02 and 7.11-7.58 (all 6H, m), 7.75-7.96 (1H, m), 8.50-8.66 (1H, m), 8.71-8.93 (1H, m)

[0993] The compound of Example 419 1H-NMR (200 MHz, CDCl3) δ ppm: 0.64-0.85, 1.10-4.00, 4.40-4.70 and 5.58-5.72 (all 17H, m), 6.36-7.62 (8H, m), 7.75-7.96 (1H, m), 8.49-8.70 (1H, m), 8.70-7.95 (1H, m)

[0994] The compound of Example 420 1H-NMR (200 MHz, CDCl3) δ ppm: 1.2-4.2, 4.45-4.6 [all 20H, m, 2.04 (s), 2.34 (s)], 5.15 and 5.22 (all 2H, each s), 6.8-7.8 (all 12H, m)

[0995] The compound of Example 421 1H-NMR (250 MHz, CDCl3) δ ppm: 1.40-1.85, 1.85-2.14, 2.68-3.10 and 4.85-5.06 (all 8H, m), 2.53 and 2.59 (all 3H, each s), 6.60 (1H, d, J=8.3 Hz), 6.85 (1H, dd, J=2.9 Hz, J=8.3 Hz), 6.96 (1H, d, J=7.9 Hz), 7.12-7.22 (2H, m), 7.29, 7.40 and 7.58 (all 2H, each s), 7.89-8.09 (1H, m), 8.43-8.66 (1H, m), 8.69-8.86 (1H, m), 8.90-9.11 (1H, m)

[0996] The compound of Example 422 1H-NMR (200 MHz, CDCl3) δ ppm: 0.75-2.10, 2.32-2.90, 3.20-3.45 and 4.70-4.90 (all 8H, m), 6.42 (1H, d, J=6.8 Hz), 6.71 (1H, dd, J=2.0 Hz, J=6.8 Hz), 6.85 (1H, d, J=2.0 Hz), 7.00-7.65 (10H, m)

[0997] The compound of Example 423 1H-NMR (200 MHz, CDCl3) δ ppm: 1.36-1.73, 1.84-2.25, 2.65-3.16 and 4.93-5.16 (all 8H, m), 6.61 (1H, d, J=8.3 Hz), 6.90 (1H, dd, J=2 Hz, J=8.3 Hz), 7.08-7.70 (10H, m)

[0998] The compound of Example 424 1H-NMR (200 MHz, CDCl3) δ ppm: 1.15-4.00 and 4.45-4.65 [all 23H, m, 1.62, 2.34 (s), 2.54 (s)], 6.55-6.65, 6.82-7.01 and 7.10-7.56 (all 6H, m), 7.74-7.93 (1H, m), 8.50-8.67 (1H, m), 8.74-8.90 (1H, m)

[0999] The compound of Example 425 1H-NMR (200 MHz, CDCl3) δ ppm: 1.38-2.22, 2.65-3.15 and 4.95-5.12 (all 8H, m), 6.61 (1H, d, J=8.4 Hz), 6.80-7.00 (2H, m), 7.20-7.38 (4H, m), 7.62 (1H, d, J=9.1 Hz), 7.98 (2H, d, J=8.3 Hz), 8.09 (1H, d, J=6.9 Hz)

[1000] The compound of Example 426 1H-NMR (250 MHz, CDCl3) δ ppm: 0.90-1.90, 1.90-2.23, 2.46-2.70 and 4.67-4.90 (all 8H, m), 8.44 (1H, d, J=8.4 Hz), 6.75 (1H, dd, J=2.4 Hz, J=8.4 Hz), 6.92 (1H, d, J=2.4 Hz), 7.05-7.75 and 7.96-8.04 (all 6H, m), 8.30-8.45, 8.53-8.74 and 8.80-8.87 (all 2H, m)

[1001] The compound of Example 433 1H-NMR (250 MHz, CDCl3) δ ppm: 1.22-3.13, 3.44-3.73 and 4.71-4.93 (all 8H, m), 6.80 (1H, dd, J=2.5 Hz, J=8.5 Hz), 6.96-7.85 (9H, m), 8.63-8.76 (1H, m)

[1002] The compound of Example 436 1H-NMR (200 MHz, CDCl3) δ ppm: 1.15-4.2, 4.4-4.7 and 5.0-5.2 [all 16H, m, 2.34 (s)], 6.5-6.75 (1H, m), 6.8-7.8 [all 11H, m, 7.50 (d, J=6.7 Hz), 7.70 (d, J=5.7 Hz)]

[1003] The compound of Example 438 1H-NMR (250 MHz, CDCl3) δ ppm: 1.22-3.95, 4.43-4.62 and 5.03-5.24 [all 30H, m), 2.34 (s)], 6.56 and 6.63 (all 1H, each d, J=8.3 Hz), 6.89-7.32 (4H, m), 7.37-7.55 (2H, m)

[1004] The compound of Example 440 1H-NMR (200 MHz, CDCl3) δ ppm: 0.84-4.00 and 4.39-4.60 (all 22H, m), 6.23-6.39 (2H, m), 6.50-6.66 (1H, m), 6.82-6.99 (1H, m), 6.99-7.15 (3H, m), 7.15-7.36 (2H, m), 7.42-7.62 (2H, m)

[1005] The compound of Example 441 1H-NMR (200 MHz, CDCl3) δ ppm: 0.80-4.00 and 4.38-4.65 [all 32H, m, 1.92 (s), 3.23 (s)], 5.85 and 5.87 (all 2H, each s), 6.57 (1H, d, J=8.5 Hz), 6.80-7.20 (4H, m), 7.45-7.65 (2H, m)

[1006] The compound of Example 444 1H-NMR (200 MHz, CDCl3) δ ppm: 1.57-2.34 (4H, m), 2.51-2.90 (2H, m), 4.74-5.23 (2H, m), 6.53-6.76 (2H, m), 6.91-7.62 (9H, m)

[1007] The compound of Example 445 1H-NMR (200 MHz, CDCl3) δ ppm: 1.75-2.0, 2.2-3.10 and 3.45-4.10 (all 18H, m), 4.65 (2H, s), 6.66-7.70 [all 11H, m, 6.67 (d, J=8.6 Hz)], 7.59 (d, J=8.5 Hz), 8.80 (1H, s)

[1008] The compound of Example 446 1H-NMR (200 MHz, CDCl3) δ ppm: 1.8-2.0 and 2.25-2.50 (all 6H, m), 2.31 (3H, s), 2.60 (1H, dd, J=15.7 Hz, J=8.3 Hz), 2.80 (1H, dd, J=15.7 Hz, J=5.7 Hz), 3.45-3.60 (3H, m), 3.60-3.80 (2H, m), 3.89 (2H, t, J=6.6 Hz), 4.60 (2H, s), 6.67 (1H, d, J=8.7 Hz), 6.88 (1H, dd, J=8.7 Hz, J=2.2 Hz), 7.00-7.50 (8H, m), 7.56 (2H, d, J=8.6 Hz), 8.41 (1 H, s)

[1009] The compound of Example 447 1H-NMR (200 MHz, CDCl3) δ ppm: 1.65-2.0 and 2.1-2.55 [all 12H, m, 2.32 (s), 2.35 (s)], 2.60 (1H, dd, J=15.7 Hz, J=8.2 Hz), 2.80 (1H, dd, J=15.7 Hz, J=5.8 Hz), 3.48-3.52 and 3.67-3.72 (all 5H, m), 3.89 (2H, t, J=6.6 Hz), 4.59 (2H, s), 6.67 (1H, d, J=8.6 Hz), 6.78 (2H, d, J=8 Hz), 6.87 (2H, d, J=8.6 Hz), 7.20 (2H, d, J=8 Hz), 7.37 (2H, d, J=8.6 Hz), 7.55 (2H, d, J=8.6 Hz), 8.37 (1H, s)

[1010] The compound of Example 448 1H-NMR (200 MHz, CDCl3) δ ppm: 1.70-2.10, 2.20-2.90 and 3.50-4.0 [all 21H, m, 2.23 (s), 2.31 (s)], 4.71 (2H, s), 6.68 (1H, d, J=8.6 Hz), 6.85-7.03, 7.15-7.43 and 7.60-7.67 (all 11H, m), 9.57 (1H, s)

[1011] The compound of Example 450 1H-NMR (200 MHz, CDCl3) δ ppm: 0.96-4.70 (29H, m), 1.45 (3H, t, J=7.0 Hz), 4.07 (2H, q, J=7.0 Hz), 5.58-7.36 (7H, m)

[1012] The compound of Example 455 1H-NMR (200 MHz, CDCl3) δ ppm: 0.95-4.00, 4.42-4.63 and 5.04-5.18 (all 22H, m), 6.46-6.67 (1H, m), 6.79-6.95 (1H, m), 6.95-7.25 (4H, m), 7.32-7.51 (2H, m), 7.52-7.75 (2H, m)

[1013] The compound of Example 456 1H-NMR (200 MHz, CDCl3) δ ppm: 0.95-3.93, 4.41-4.62 and 5.01-5.20 [all 25H, m, 2.24 (s)], 6.45-6.62 (1H, m), 6.72-6.95 (2H, m), 6.95-7.08 (1H, m), 7.10-7.45 (3H, m), 7.45-7.69 (2H, m)

[1014] The compound of Example 459 1H-NMR (200 MHz, CDCl3) δ ppm: 1.42 (6H, t, J=7.2 Hz), 1.75-2.05 (1H, m), 2.15-2.40 (1H, m), 2.40-3.90 (11H, m), 3.94 (2H, t, J=6.5 Hz), 6.73-7.15 (3H, m), 7.25-7.60 (10H, m), 8.35-8.75 (1H, m), 11.3-11.7 (1H, m)

[1015] The compound of Example 460 1H-NMR (200 MHz, CDCl3) δ ppm: 1.24 (3H, t, J=7 Hz), 1.4-1.5, 1.85-3.30, 3.40-4.20 and 4.65-4.85 (all 15H, m), 3.72 (2H, q, J=7 Hz), 6.8-7.7 (13H, m), 12.6-12.9 (1H, m)

[1016] The compound of Example 461 1H-NMR (200 MHz, CDCl3) δ ppm: 1.03 (6H, t, J=7 Hz), 1.75-2.0 (1H, m), 2.10-2.30 (1H, m), 2.35-2.90 (8H, m), 3.35-3.80(3H, m), 3.90 (2H, t, J=6.6 Hz), 6.72 (1H, d, J=8.6 Hz), 6.8-7.0 (2H, m), 7.23 (1H, d, J=2.2 Hz), 7.35-7.66 (9H, m)

[1017] The compound of Example 462 1H-NMR (200 MHz, CDCl3) δ ppm: 1.03 (3H, t, J=7.2 Hz), 1.75-2.0 (1H, m), 2.15-2.40 (1H, m), 2.40-2.90 (8H, m), 3.50-3.60 (3H, m), 3.65-3.85 (2H, m), 3.93 (2H, m), 6.75-7.0 and 7.2-7.65 (all 12H, m)

[1018] The compound of Example 463 1H-NMR (200 MHz, CDCl3) δ ppm: 1.20-1.70,1.70-3.0, 3.0-3.6, 3.6-3.8 and 3.8-4.0 (all 32H, m), 6.73 (1H, d, J=8.6 Hz), 6.87 (1H, dd, J=8.6 Hz, J=2.4 Hz), 7.13 (2H, d, J=8 Hz), 7.23 (1H, d, J=2.4 Hz), 7.33 (2H, d, J=8 Hz), 8.4-8.7 (1H, m), 11.2-11.6 (1H, m)

[1019] The compound of Example 464 1H-NMR (200 MHz, CDCl3) δ ppm: 1.10 (3H, t, J=7.2 Hz), 1.2-1.65, 1.7-2.0, 2.1-2.9, 3.4-3.6, 3.6-3.8 and 3.8-4.0 (all 28H, m), 6.77 (1H, d, J=8.7 Hz) 6.90 (1H, dd, J=8.7 Hz, J=2.3 Hz), 7.13 (2H, d, J=8.2 Hz), 7.19 (1H, d, J=2.3 Hz), 7.31 (2H, d, J=8.2 Hz)

[1020] The compound of Example 467 1H-NMR (250 MHz, CDCl3) δ ppm: 1.10-2.10, 2.55-4.05, 4.45-4.61 and 4.68-4.71 (all 41H, m), 6.94-7.38 (3H, m), 12.00-12.27 (1H, brs)

[1021] The compound of Example 469 1H-NMR (200 MHz, CDCl3) δ ppm: 1.20-2.24 (5H, m), 2.63-3.31 (3H, m), 3.70 and 3.75 (all 3H, s), 4.08-5.20 (1H, m), 6.46-6.62 (1H, m), 6.36-7.00 (1H, m), 7.10-7.48 (3H, m), 8.43-8.56 (2H, m)

[1022] The compound of Example 470 1H-NMR (200 MHz, CDCl3) δ ppm: 1.05-5.08 (26H, m), 6.15-7.53 (16H, m)

[1023] The compound of Example 471 1H-NMR (200 MHz, CDCl3) δ ppm: 0.97-2.20, 2.20-4.06 and 4.40-4.63 [all 36H, m), 1.41 (t, J=7.2 Hz), 1.71 (s), 3.31 (s)], 6.59 (1H, d, J=8.5 Hz), 6.84-7.60 (6H, m), 12.7-13.4 (1H, brs)

[1024] The compound of Example 472 1H-NMR (200 MHz, CDCl3) δ ppm: 1.20-226, 2.50-4.10, 4.40-4.60 and 5.00-5.15 (all 29H, m), 6.58 (1H, d, J=8.2 Hz), 6.65-7.48 (6H, m), 12.12 (1H, brs)

[1025] The compound of Example 473 1H-NMR (200 MHz, CDCl3) δ ppm: 1.30-2.20, 2.50-4.10, 4.38-4.60 and 4.98-5.16 (all 29H, m), 6.50-7.20 (5H, m), 7.36 (2H, d, J=8.6 Hz), 12.15 (1H, brs)

[1026] The compound of Example 476 1H-NMR (200 MHz, CDCl3) δ ppm: 1.16-4.10 and 4.30-4.53 (all 35H, m), 6.47-6.80, 6.80-7.65 and 7.86-8.10 (all 7H, m), 15.51-15.98 (1H, br)

[1027] The compound of Example 477 1H-NMR (200 MHz, CDCl3) δ ppm: 1.12-2.11 (4H, m), 2.45-3.78 (5H, m), 4.23-5.10 (1H, m), 6.61-7.75 (14H, m)

[1028] The compound of Example 478 1H-NMR (200 MHz, CDCl3) δ ppm: 0.62 (1.5H, d, J=6.5 Hz), 0.99 (1.5H, d, J=6.5 Hz), 1.03-5.74 (14H, m), 6.43-7.80 (11H, m)

[1029] The compound of Example 479 1H-NMR (200 MHz, CDCl3) δ ppm: 0.80-3.90, 4.41-4.64 an 5.05-5.70 (all 35H, m), 6.49-6.63 (1H, m), 6.71-7.20 (4H, m), 7.20-7.50 (2H, m)

[1030] The compound of Example 480 1H-NMR (200 MHz, CDCl3) δ ppm: 0.92-2.25, 2.38-3.27, 3.27-4.00, 4.50-4.60 and 4.85-5.02 (all 29H, m), 6.62-7.45 (6H, m)

[1031] The compound of Example 481 1H-NMR (200 MHz, CDCl3) δ ppm: 0.82-4.17, 4.36-4.60 and 5.07-5.13 [all 26H, m, 2.99 (s), 3.23 (s)], 6.40-6.66 (1H, m), 6.75-7.78 (8H, m), 7.84 (1H, d, J=3.7 Hz)

[1032] The compound of Example 482 1H-NMR (200 MHz, CDCl3) δ ppm: 0.77-1.14, 1.14-2.24, 2.24-4.04, 4.33-4.53 and 4.97-5.13 [all 27H, m, 2.89 (s), 3.14 (s)], 6.42-6.61 (1H, m), 6.77-7.10 (2H, m), 7.28-7.80, 7.80-8.12 [all 6H, m, 7.88 (s)]

[1033] The compound of Example 484 1H-NMR (200 MHz, CDCl3) δ ppm: 1.19-5.33 (22H, m), 6.49-7.32 (12H, m), 11.92-12.70 (1H, m)

[1034] The compound of Example 485 1H-NMR (200 MHz, CDCl3) δ ppm: 1.20-5.28 (20H, m), 1.38 (3H, t, J=7.2 Hz), 3.32 (3H, s), 6.61 (1H, d, J=8.3 Hz), 6.91 (1H, dd, J=8.3 Hz, J=2.2 Hz), 7.03 (1H, d, J=2.2 Hz), 7.18-7.76 (9H, m), 11.94 (1H, brs)

[1035] The compound of Example 486 1H-NMR (200 MHz, CDCl3) δ ppm: 1.19-5.13 (24H, m),1.35 (3H, t, J=7.3 Hz), 1.45 (3H, t, J=7.0 Hz), 4.08 (2H, q, J=7.0 Hz), 6.18-7.46 (6H, m), 11.59-12.58 (1H, m)

[1036] The compound of Example 487 1H-NMR (200 MHz, CDCl3) δ ppm: 0.93-3.98 (26H, m), 4.51-5.15 (1H, m), 4.97 and 5.10 (all 2H, s), 6.23-7.51 (11H, m)

[1037] The compound of Example 488 1H-NMR (200 MHz, CDCl3) δ ppm: 0.90-2.12, 2.12-2.40, 2.40-3.63 and 4.45-4.84 (all 38H, m), 6.98-7.35 (2H, m), 7.38-7.44 (1H, m)

[1038] The compound of Example 489 1H-NMR (200 MHz, CDCl3) δ ppm: 1.06-5.19 (36H, m), 6.16-7.49 (6H, m), 11.28-11.99 (1H, m)

[1039] The compound of Example 490 1H-NMR (200 MHz, CDCl3) δ ppm: 1.32-4.57 (22H, m), 1.45 (3H, t, J=7.0 Hz), 2.58 and 2.60 (all 3H, s), 4.08 (2H, q, J=7.0 Hz), 6.43-6.63 (2H, m), 7.05-7.44 (4H, m), 12.15 (1H, brs)

[1040] The compound of Example 491 1H-NMR (200 MHz, CDCl3) δ ppm: 1.20-5.21 (31H, m), 6.11-7.61 (6H, m), 8.54-8.72 (1H, m), 11.27-12.03 (1H, m)

[1041] The compound of Example 492 1H-NMR (200 MHz, CDCl3) δ ppm: 1.23-5.03 (25H, m), 1.46 (3H, t, J=7.0 Hz), 4.08 (2H, q, J=7.0 Hz), 6.16-7.44 (6H, m), 12.47 (1H, brs)

[1042] The compound of Example 493 1H-NMR (200 MHz, CDCl3) δ ppm: 1.11-4.67 (29H, m), 4.97, 5.10 (all 2H, s), 6.22-7.51 (11H, m), 11.43-12.04 (1H, m)

[1043] The compound of Example 494 1H-NMR (200 MHz, CDCl3) δ ppm: 1.21-4.62 (26H, m), 4.98 and 5.11 (all 2H, s), 6.22-7.51 (11H, m), 8.55-8.71 (1H, m), 11.39-11.81 (1H, m)

[1044] The compound of Example 495 1H-NMR (200 MHz, CDCl3) δ ppm: 1.21-4.90 (22H, m), 1.34 (3H, t, J=7.3 Hz), 4.98 and 5.11 (all 2H, s), 6.27-7.53 (11H, m), 12.48 (1H, brs)

[1045] The compound of Example 496 1H-NMR (200 MHz, CDCl3) δ ppm: 0.83-3.98 (24H, m), 2.99 and 3.15 (all 3H, s), 3.62 and 3.86 (all 3H, s), 4.49-5.19 (1H, m), 4.97 and 5.10 (all 2H, s), 6.23-7.53 (11H, m)

[1046] The compound of Example 497 1H-NMR (200 MHz, CDCl3) δ ppm: 1.18-2.20, 2.60-4.55 (all 26H, m), 6.45-6.55 (1H, m), 6.80-6.95 (1H, m), 6.95-7.60 (4H, m), 7.90-8.08 (1H, m), 11.86 (1H, brs)

[1047] The compound of Example 498 1H-NMR (200 MHz, CDCl3) δ ppm: 1.20-2.20, 2.55-3.40, 3.40-4.10, 4.35-4.53 and 4.96-5.20 (all 26H, m), 6.53 (1H, d, J=8 Hz), 6.91 (1H, dd, J=0.2 Hz, J=8 Hz), 7.04 (1H, d, J=0.2 Hz), 7.13 (2H, d, J=8.6 Hz), 7.40 (2H, d, J=8.6 Hz), 12.15 (1H, s)

[1048] The compound of Example 499 1H-NMR (200 MHz, CDCl3) δ ppm: 1.20-2.20, 2.20-3.45, 3.45-4.10 and 4.45-4.65 (all 29H, m), 6.50-6.62, 6.75-7.55 and 7.95-8.07 (all 7H, m), 11.8-12.2 (1H, m)

[1049] The compound of Example 500 1H-NMR (200 MHz, CDCl3) δ ppm: 1.25-3.40, 3.40-4.15 and 4.40-4.60 (all 29H, m), 6.50-6.62, 6.80-7.45 and 7.85-7.95 (all 7H, m), 12.06 (1H, brs)

[1050] The compound of Example 501 1H-NMR (200 MHz, CDCl3) δ ppm: 1.20-4.10, 4.45-4.60 and 5.00-5.20 (all 29H, m), 6.56 (1H, d, J=6.4 Hz), 6.80-7.50 (5H, m), 7.96 (1H, d, J=8.2 Hz), 12.01 (1H, brs)

[1051] The compound of Example 502 1H-NMR (200 MHz, CDCl3) δ ppm: 1.20-4.18 and 4.50-4.70 (all 29H, m), 6.60-6.90, 6.90-7.51, 7.51-7.66 and 8.15-8.22 (all 7H, m), 11.8-12.25 (1H, br)

[1052] The compound of Example 503 1H-NMR (200 MHz, CDCl3) δ ppm: 0.78-3.95, 4.42-4.60 and 5.05-5.21 (all 26H, m), 6.49-6.62 (1H, m), 6.82-6.98 (1H, m), 6.98-7.52 (6H, m)

[1053] The compound of Example 504 1H-NMR (200 MHz, CDCl3) δ ppm: 1.16-4.06, 4.43-4.64 and 4.92-5.10 (all 26H, m), 6.72-7.65 (7H, m), 11.87-12.18 (1H, br)

[1054] The compound of Example 505 1H-NMR (200 MHz, CDCl3) δ ppm: 1.00-3.95, 4.20-4.44 and 4.90-5.05 (all 22H, m), 5.10-6.50 (1H, br), 6.65-6.76 (1H, m), 6.90-7.05 (1H, m), 7.20-7.35 (1H, m), 7.35-7.50 (2H, m), 7.70-7.85 (2H, m)

[1055] The compound of Example 508 1H-NMR (250 MHz, CDCl3) δ ppm: 0.65-0.82, 1.00-2.17, 2.17-2.95, 2.95-3.51, 3.55-3.90, 4.18-4.35, 4.42-4.63, 5.03-5.18 and 5.50-5.75 (all 25H, m), 6.51-6.68 (1H, m), 6.85-7.45 (5H, m), 7.51-7.65 (1H, m)

[1056] The compound of Example 509 1H-NMR (200 MHz, CDCl3) δ ppm: 0.49 (3H, d, J=6.3 Hz), 0.95 (3H, d, J=6.3 Hz), 1.1-4.2 [all 16H, m, 3.02 (s)], 6.55-6.80 (3H, m), 7.15-7.45 (5H, m)

[1057] The compound of Example 510 1H-NMR (200 MHz, CDCl3) δ ppm: 1.0-2.2, 2.4-4.0 and 4.5-4.6 [all 25H, m, 2.87 (s), 3.0 (s)], 6.1-7.5 [all 7H, m, 6.26 (dd, J=8.8 Hz, J=2.5 Hz)]

[1058] The compound of Example 511 1H-NMR (200 MHz, CDCl3) δ ppm: 1.10-5.35 [24H, m, 2.33 (s)], 6.75-8.26 (7H, m)

[1059] The compound of Example 512 1H-NMR (200 MHz, CDCl3) δ ppm: 1.1-1.5, 1.5-4.0, 4.4-4.7 and 4.9-5.1 (all 28H, m, 2.02 (s), 2.18 (s)), 6.13-7.70 (7H, m)

[1060] The compound of Example 516 1H-NMR (200 MHz, CDCl3) δ ppm: 1.30-1.85, 1.85-2.22, 2.61-3.16 and, 4.82-5.06 (8H, m), 2.50 and 2.56 (all 3H, each s), 6.55-6.65, 6.78-6.95 and 7.10-7.60 (all 8H, m), 8.52-8.70 (2H, m)

[1061] The compound of Example 517 1H-NMR (200 MHz, CDCl3) δ ppm: 1.30-2.30, 2.30-3.15, 3.36-3.60 and 4.98-5.08 [all 11H, m, 2.49 (s), 2.54 (s)], 6.60 (1H, d, J=8.4 Hz), 6.75-6.95 (2H, m), 6.95-7.10 (1H, m), 7.10-7.51 (5H, m), 8.38-8.87 (2H, m)

[1062] The compound of Example 520 1H-NMR (200 MHz, CDCl3) δ ppm: [all 6H, m, 0.651 (d, J=6.5 Hz), 1.02 (d, J=6.5 Hz), 1.15 (d, J=6.5 Hz, 1.22 (d, J=6.5 Hz)], 1.25-2.22, 2.45-2.90, 3.00-3.21, 3.50-4.00 and 4.44-4.67 [all 13H, m, 2.57 (s), 2.63 (s)], 6.50-7.96 and 8.65-8.95 (11H, m)

[1063] The compound of Example 521 1H-NMR (200 MHz, CDCl3) δ ppm: 1.1-4.9 [all 26H, m, 3.06 (s)], 6.65-7.75 (all 7H, m), 12.4-13.2 (1H, m)

[1064] The compound of Example 523 1H-NMR (200 MHz, CDCl3) δ ppm: 1.18-2.20, 2.29-3.12, 3.29-3.61 and 4.81-5.10 [all 21H, m, 2.34 (s)], 6.23 (1H, dd, J=8.72 Hz, J=8.73 Hz), 6.50 (1H, d, J=2.48 Hz), 6.56-7.49 (5H, m)

[1065] The compound of Example 524 1H-NMR (200 MHz, CDCl3) δ ppm: 0.89 (6H, d, J=6.54 Hz), 1.32-2.20, 2.30-3.31, 3.42-3.95 and 4.82-5.12 (all 19H, m), 6.39-7.49 (7H, m)

[1066] The compound of Example 525 1H-NMR (200 MHz, CDCl3) δ ppm: 1.10-2.20 and 2.20-4.90 (all 23H, m), 6.35-6.69, 6.69-7.00, 7.00-8.34 and 8.65-9.16 (all 10H, m), 1.65-12.8 (1H, br)

[1067] The compound of Example 526 1H-NMR (200 MHz, CDCl3) δ ppm: 0.64, 0.98,1.16 and 1.19 (all 6H, each d, J=6.5 Hz), 1.20-1.49, 1.49-2.23, 2.23-4.60 and 4.95-5.12 [all 13H, m, 2.58 (s), 2.65 (s)], 6.05-6.50, 6.50-6.65, 6.70-6.95, 7.05-7.45, 7.45-7.90, 7.90-8.33 and 8.75-9.15 (all 12H, m)

[1068] The compound of Example 529 1H-NMR (200 MHz, CDCl3) δ ppm: 1.13-4.88 (20H, m), 1.19 and 1.35 (all 9H, s), 2.46, 2.49 and 2.51 (all 6H, s), 6.58-7.47 (7H, m), 12.76 (1H, brs)

[1069] The compound of Example 530 1H-NMR (200 MHz, CDCl3) δ ppm: 1.35-2.25, 2.36-3.60 and 4.47-5.09 [all 11H, m, 2.52 (s), 2.58 (s)], 6.60-6.75 (1H, m), 6.75-7.09 (8H, m), 8.52-8.75 (2H, m)

[1070] The compound of Example 531 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.05-2.0, 2.5-4.0 and 4.2-4.6 (all 24H, m), 6.14-7.5 [all 7H, m, 6.16 (d, J=8.8 Hz)], 11.1-11.5 (2H, m)

[1071] The compound of Example 532 1H-NMR (200 MHz, CDCl3) δ ppm: 1.3-2.4, 2.7-4.1, 4.5-4.7 and 5.0-5.2 (all 9H, m), 6.7-7.8 (12H, m)

[1072] The compound of Example 534 1H-NMR (200 MHz, CDCl3) δ ppm: 1.30-2.25, 2.40-3.50 and 4.86-5.08 [all 11H, m, 2.53 (s), 2.58 (s)], 6.00-7.60 and 8.55-8.85 (all 10H, m)

[1073] The compound of Example 535 1H-NMR (200 MHz, CDCl3) δ ppm: 1.10-4.90 (23H, m), 6.50-6.66, 6.80-7.68 and 8.60-8.91 (all 9H, m), 12.77-13.45 (1H, br)

[1074] The compound of Example 541 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.00-2.11, 2.12-3.90 and 4.18-4.71 [all 34H, m, 2.32 (s), 2.36 (s)], 6.40-7.55 (6H, m), 9.82-10.16 and 10.80-11.24 (all 1H, m)

[1075] The compound of Example 542 1H-NMR (200 MHz, CDCl3) δ ppm: 1.35-2.15, 2.6-3.15, 3.65-4.0, 4.47, 4.57 and 4.85-5.0 [all 16H, m, 4.47 (s), 4.57 (s)], 6.48 and 6.7-7.45 [all 12H, m, 6.48 (s)]

[1076] The compound of Example 544 1H-NMR (200 MHz, CDCl3) δ ppm: 1.16-4.92 (20H, m), 2.53 and 2.59 (all 3H, s), 6.54-6.75 (1H, m), 6.91-7.18 (2H, m), 7.23-7.68 (8H, m), 12.83 (1H, brs)

[1077] The compound of Example 545 1H-NMR (200 MHz, CDCl3) δ ppm: 1.17-5.20 (20H, m), 4.93 and 5.11 (all 2H, s), 6.53-7.56 (12H, m), 12.34-13.15 (1H, m)

[1078] The compound of Example 547 1H-NMR (200 MHz, CDCl3) δ ppm: 0.82-5.25 (27H, m), 3.87 (2H, t, J=6.4 Hz), 6.53-6.80 (2H, m), 6.83-7.68 (6H, m), 12.32-13.22 (1H, m)

[1079] The compound of Example 553 1H-NMR (200 MHz, CDCl3) δ ppm: 1.11-4.21, 4.49-4.71 and 4.98-5.20 (all 25H, m), 6.28-7.61 (11H, m)

[1080] The compound of Example 554 1H-NMR (200 MHz, CDCl3) δ ppm: 1.19-4.04, 4.48-4.71 and 4.97-5.19 [all 26H, m, 2.17 (s), 2.21 (s)], 6.42-7.74 (12H, m)

[1081] The compound of Example 555 1H-NMR (200 MHz, CDCl3) δ ppm: 2.57 (4H, t, J=5.10 Hz), 3.32 (4H, t, J=5.10 Hz), 3.56 (2H, s), 3.86 (3H, s), 6.74 (1H, dd, J=8.94 Hz, J=8.96 Hz), 6.85 (1H, d, J=2.55 Hz), 7.25-7.45 (5H, m), 7.83 (1H, d, J=8.91 Hz)

[1082] The compound of Example 556 1H-NMR (200 MHz, CDCl3) δ ppm: 1.03-2.22, 2.60-3.15, 3.90-4.28 and 4.80-5.00 [all 28H, m, 1.45 (s), 3.98 (d, J=6.31 Hz)], 6.68-7.42 and 7.58-7.71 (all 7H, m)

[1083] The compound of Example 558 1H-NMR (200 MHz, DMSO-d6) δ ppm: 0.9-2.2, 2.6-3.2 and 4.5-4.9 [all 15H, m, 4.51 (s), 4.58 (s)], 6.8-7.15, 7.15-7.40 and 7.40-7.90 (all 12.2H, m), 8.47 and 8.7 (all 0.8H, each s)

[1084] The compound of Example 559 1H-NMR (200 MHz, CDCl3) δ ppm: 0.80-4.08 and 4.42-4.69 [all 29H, m, 2.40 (s)], 6.58-7.78 [all 8H, m, 7.51 (d, J-.2.01 Hz)]

[1085] The compound of Example 560 1H-NMR (200 MHz, CDCl3) δ ppm: 1.0-1.25, 1.25-2.25, 2.5-3.7 and 4.4-5.0 (all 15H, m), 6.73-7.75 (all 10H, m), 8.53 (2H, d, J=5 Hz)

[1086] The compound of Example 562 1H-NMR (200 MHz, CDCl3) δ ppm: 1.17-4.86 (26H, m), 6.50-7.65 (10H, m), 12.67 (1H, brs)

[1087] The compound of Example 563 1H-NMR (200 MHz, DMSO-d6) δ ppm: 0.96-2.35 and 2.36-4.97 (all 20H, m), 6.79-8.06 (12H, m), 10.02-10.46 and 11.00-11.60 (all 1H, m)

[1088] The compound of Example 564 1H-NMR (200 MHz, CDCl3) δ ppm: 0.52-2.22, 2.23-4.24, 4.34-4.71 and 4.91-5.17 [all 14H, m, 0.66 (t, J=7.3 Hz)], 5.53-5.74 and 6.29-6.58 (all 1H, m), 6.89-7.88 (12H, m)

[1089] The compound of Example 565 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.08-2.21, 2.23-4.08 and 4.21-5.11 [all 26H, m, 2.31 (s), 2.44 (s)], 6.46-7.78 (11H, m), 10.00-10.28 and 10.96-11.45 (all 1H, m)

[1090] The compound of Example 566 1H-NMR (200 MHz, CDCl3) δ ppm: 1.16-2.20, 2.28-4.10, 4.42-4.71 and 4.89-5.11 [all 25H, m, 2.42 (s), 2.56 (s)], 6.59-7.68 (11H, m)

[1091] The compound of Example 567 1H-NMR (200 MHz, DMSO-d6) δ ppm: 0.79-2.19, 2.29-3.80 and 3.96-4.67 (all 23H, m), 6.52-7.48 and 7.49-8.45 (11H, m), 9.83-10.21 and 10.86-11.51 (all 1H, each br)

[1092] The compound of Example 572 1H-NMR (200 MHz, CDCl3) δ ppm: 0.57-0.90, 1.03-2.22, 2.27-4.69 and 5.49-5.71 [all 20H, m, 0.67 (t, J=7.3 Hz), 2.44 (s), 2.59 (s)], 5.49-5.71 and 6.36-7.65 (all 12H, m)

[1093] The compound of Example 577 1H-NMR (200 MHz, CDCl3) δ ppm: 1.3-2.2, 2.65-3.2, 4.0-4.4 and 4.8-5.0 (all 11H, m), 6.18 (1H, dd, J=8.4 Hz, J=2.4 Hz), 6.48 (1H, d, J=2.2 Hz), 6.69 (1H, d, J=8.4 Hz), 6.85-7.45 (9H, m)

[1094] The compound of Example 578 1H-NMR (200 MHz, CDCl3) δ ppm: 1.2-2.2, 2.5-3.4, 4.15-4.4 and 4.7-5.1 (all 14H, m), 6.15 (0.88H, d, J=8 Hz), 6.43 (0.94H, s), 6.67 (1.07H, d, J=8 Hz), 6.8-7.5 (9.1H, m)

[1095] The compound of Example 583 1H-NMR (200 MHz, CDCl3) δ ppm: 0.95-4.9 [all 26H, m, 1.10 (t, J=7.2 Hz), 2.47 (d, J=4 Hz)], 6.8-7.2, 7.2-7.55, 7.55-8.25 and 8.25-8.60 [all 14H, m, 8.44 (s)]

[1096] The compound of Example 584 1H-NMR (200 MHz, CDCl3) δ ppm: 0.666 (3H, t, J=7.3 Hz), 1.50-4.00 (17H, m), 6.40-7.20 (13H, m)

[1097] The compound of Example 585 1H-NMR (200 MHz, CDCl3) δ ppm: 1.00-4.20 and 4.40-4.35 [all 23H, m, 2.50 (s), 2.54 (s)], 6.80-7.65 (12H, m)

[1098] The compound of Example 586 1H-NMR (200 MHz, CDCl3) δ ppm: 1.45-3.13, 3.20-4.00 and 4.20-5.18 (all 13H, m), 6.62-7.66 (12H, m)

[1099] The compound of Example 589 1H-NMR (200 MHz, CDCl3) δ ppm: 0.8-3.7 and 4.85-5.15 [all 24H, m, 2.37 (s)], 5.9-7.2 [all 7H, m, 6.27 (s)]

[1100] The compound of Example 593 1H-NMR (200 MHz, CDCl3) δ ppm: 1.3-3.8, 4.2-4.8 and 4.9-5.15 [all 12H, m, 3.36 (s), 3.48 (s), 4.55 (s)], 6.6-7.95 (12H, m), 8.15-8.7 (1H, m)

[1101] The compound of Example 594 1H-NMR (200 MHz, CDCl3) δ ppm: 1.19-2.35, 2.60-3.15, 3.75-4.20, 4.30-4.61 and 4.79-5.11 (all 12H, m), 6.71-7.75 (7H, m)

[1102] The compound of Example 595 1H-NMR (200 MHz, CDCl3) δ ppm: 0.75-3.30, 3.30-4.18 and 4.40-4.62 (all 20H, m), 6.55-6.72 (1H, m), 6.72-6.97 (2H, m), 6.97-7.18 (2H, m), 7.18-7.67 (7H, m)

[1103] The compound of Example 599 1H-NMR (200 MHz, CDCl3) δ ppm: 1.18-1.58, 1.58-4.29 and 4.50-4.85 [all 25H, m, 1.71 (s), 2.54 (s)], 7.05-7.72 (12H, m), 14.5-17.8 (1H, brs)

[1104] The compound of Example 601 1H-NMR (200 MHz, CDCl3) δ ppm: 1.50-2.20, 2.20-2.73 and 2.90-4.00 [all 16H, m, 1.62 (s), 2.59 (s), 3.24 (s)], 7.16-7.69 (12H, m), 9.42 (1H, s)

[1105] The compound of Example 606 1H-NMR (200 MHz, CDCl3) δ ppm: 1.15-2.00, 2.55-2.90, 3.35-3.70 and 4.40-4.60 [all 27H, m, 1.57 (s)], 7.00-7.34 (3H, m)

[1106] The compound of Example 607 1H-NMR (200 MHz, CDCl3) δ ppm: 1.15-2.09, 2.56-2.97, 3.30-3.65, 4.40-4.60 and 4.71-4.82 (all 24H, m), 6.95-7.28 (3H, m)

[1107] The compound of Example 608 1H-NMR (250 MHz, DMSO-d6) δ ppm: 1.15-1.55, 1.70-2.35, 2.55-3.16, 3.44-3.65, 4.20-4.40 and 4.70-5.07 (all 9H, m), 6.49-6.57, 6.57-6.85, 6.9-7.05 and 7.05-7.5 (all 8H, m), 7.62-7.75 (2H, m)

[1108] The compound of Example 609 1H-NMR (250 MHz, DMSO-d6) δ ppm: 1.15-2.14, 2.14-4.40 and 4.90-5.54 (all 12H, m), 6.65 and 6.72 (all 1H, each d, J=8.3 Hz), 6.92-7.46 and 7.60-7.81 (all 8H, m)

[1109] The compound of Example 610 1H-NMR (200 MHz, CDCl3) δ ppm: 2.15-2.63, 2.27-3.18, 3.55-4.06 and 5.82-6.03 (all 8H, m), 7.46 (1H, d, J=8.3 Hz), 7.78 (1H, dd, J=2.4 Hz, J=8.3 Hz), 8.16 (1H, d, J=2.4 Hz), 8.21-8.33 (2H, m), 8.54-8.70 (2H, m), 10.87 (1H, s)

[1110] The compound of Example 611 1H-NMR (200 MHz, CDCl3) δ ppm: 1.49-1.76, 1.86-2.22, 2.67-3.09 and 4.90-5.08 (all 8H, m), 6.51 (1H, d, J=8.3 Hz), 6.89 (1H, dd, J=2 Hz, J=8.3 Hz), 7.13-7.35 (3H, m), 7.42-7.56 (2H, m)

[1111] The compound of Example 613 1H-NMR (200 MHz, CDCl3) δ ppm: 1.27-1.70, 1.80-2.30, 2.68-3.37, 3.40-3.85, 4.35-4.58 and 5.08-5.20 (all 9H, m), 6.47 and 6.54 (all 1H, each d, J=8.3 Hz), 6.86-7.01 (1H, m), 7.15 and 7.32 (all 1H, each d, J=2 Hz), 7.35-7.56 (4H, m)

[1112] The compound of Example 614 1H-NMR (200 MHz, CDCl3) δ ppm: 0.75-3.90, 4.40-4.55 and 5.03-5.20 (all 28H, m), 6.45-6.65 (1H, m), 6.70-7.35 (6H, m), 7.65-7.95 (1H, m)

[1113] The compound of Example 615 1H-NMR (200 MHz, CDCl3) δ ppm: 0.80-3.90, 4.35-4.56, 5.08-5.20 and 6.45-6.67 (1H, m), 6.90-7.55 (6H, m), 7.80-8.25 and 8.75-8.85 (all 1H, m)

[1114] The compound of Example 616 1H-NMR (200 MHz, CDCl3) δ ppm: 1.00-3.95, 4.37-4.57 and 5.00-5.17 (all 22H, m), 6.45 and 6.50 (all 1H, each d, J=8.3 Hz), 6.90 (1H, dd, J=2.3 Hz, J=8.3 Hz), 6.96-7.06 and 7.29-7.36 (all 2H, m), 7.44-7.68 (4H, m)

[1115] The compound of Example 617 1H-NMR (200 MHz, CDCl3) δ ppm: 0.85-3.92, 4.35-4.52 and 4.95-5.15 (all 26H, m), 6.40-6.55 (1H, m), 6.85-6.95 (1H, m), 6.95-7.15 (1H, m), 7.30-7.70 (4H, m)

[1116] The compound of Example 618 1H-NMR (200 MHz, CDCl3) δ ppm: 1.15-2.20, 2.52-3.90, 4.40-4.59 and 5.08-5.26 (all 22H, m), 6.54-6.68 (1H, m), 6.87-7.44 (6H, m)

[1117] The compound of Example 619 1H-NMR (200 MHz, CDCl3) δ ppm: 1.15-2.21, 2.47-3.01, 3.07-3.32, 3.41-3.78, 4.35-4.57 and 5.08-5.23 (all 19H, m), 6.00-6.51 (1H, brs), 6.59 (1H, d, J=8.3 Hz), 6.89-7.41 (6H, m)

[1118] The compound of Example 622 1H-NMR (200 MHz, CDCl3) δ ppm: 0.76-2.21, 2.22-4.31, 4.38-4.64 and 5.01-5.24 [all 23H, m, 2.41 (s), 2.46 (s)], 6.38-7.43 (6H, m)

[1119] The compound of Example 623 1H-NMR (200 MHz, CDCl3) δ ppm: 0.73-5.18 (24H, m), 6.52-8.03 (8H, m), 12.50-13.30 (1H, m)

[1120] The compound of Example 624 1H-NMR (200 MHz, CDCl3) δ ppm: 0.93 (3H, t, J=7.2 Hz), 1.10-2.30 (8H, m), 2.56-4.30 (5H, m), 3.65 and 3.70 (all 3H, s), 3.88 (2H, t, J=6.5 Hz), 4.38-5.33 (1H, m), 6.51-7.40 (8H, m)

[1121] The compound of Example 626 1H-NMR (200 MHz, CDCl3) δ ppm: 1.20-2.22 (4H, m), 2.40-5.23 (5H, m), 2.52 and 2.56 (all 3H, s), 3.72 and 3.73 (all 3H, s), 6.45-7.70 (10H, m)

[1122] The compound of Example 627 1H-NMR (200 MHz, CDCl3) δ ppm: 1.17-2.21 (4H, m), 2.61-3.02 (2H, m), 3.09-3.85 (1H, m), 3.69 (3H, s), 4.01-4.27 (1H, m), 4.43-5.18 (1H, m), 4.94 and 5.10 (all 2H, s), 6.46-6.67 (1H, m), 6.83-7.50 (11H, m)

[1123] The compound of Example 629 1H-NMR (200 MHz, CDCl3) δ ppm: 1.09-2.32 (4H, m), 2.56-5.33 (5H, m), 3.69 and 3.74 (all 3H, s), 6.53-7.78 (12H, m)

[1124] The compound of Example 630 1H-NMR (200 MHz, CDCl3) δ ppm: 1.12-2.18 (4H, m), 1.18 and 1.34 (all 9H, s), 2.33-5.24 (5H, m), 2.45 and 2.49 (all 3H, s), 7.32 (3H, s), 6.43-7.51 (7H, m)

[1125] The compound of Example 631 1H-NMR (200 MHz, CDCl3) δ ppm: 1.08-2.25 (4H, m), 1.18 and 1.33 (all 9H, s), 2.34-3.96 (5H, m), 2.45 and 2.50 (all 3H, s), 6.47-7.50 (7H, m), 9.00 (1H, brs)

[1126] The compound of Example 632 1H-NMR (200 MHz, CDCl3) δ ppm: 1.15-2.35 (7H, m), 2.58-3.28 (3H, m), 3.35-5.20 (10H, m), 6.15-7.56 (6H, m)

[1127] The compound of Example 633 1H-NMR (200 MHz, CDCl3) δ ppm: 1.16-2.22 (7H, m), 2.58-3.29 (3H, m), 3.35-4.18 (6H, m), 4.45-5.21 (1H, m), 6.12-7.48 (6H, m), 10.82 (1H, brs)

[1128] The compound of Example 634 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.13-2.21 (4H, m), 2.36-4.31 (4H, m), 2.49 (3H, s), 4.33-5.13 (1H, m), 6.76-7.88 (11H, m), 12.43 (1H, brs)

[1129] The compound of Example 637 1H-NMR (200 MHz, CDCl3) δ ppm: 1.15-2.33, 2.33-3.99, 3.99-4.31, 4.50-4.65 and 5.05-5.18 (all 15H, m), 6.50-7.70 and 8.10-8.20 (all 12H, m)

[1130] The compound of Example 640 1H-NMR (200 MHz, CDCl3) δ ppm: 1.13-2.26, 2.35-3.90, 4.43-4.66 and 5.03-5.22 (all 15H, m), 6.40-6.70 (1H, m), 6.73-6.95 (1H, m), 6.95-7.65 (6H, m), 8.50-8.75 (2H, m)

[1131] The compound of Example 641 1H-NMR (200 MHz, CDCl3) δ ppm: 1.22-2.35, 2.5-3.3, 3.4-3.9, 4.35-4.7 and 5.0-5.3 (all 18H, m), 6.65 (1H, d, J=8.3 Hz), 6.85-7.5 (9H, m), 7.6-7.8 (1H, m)

[1132] The compound of Example 642 1H-NMR (200 MHz, CDCl3) δ ppm: 1.2-1.65, 1.9-2.25, 2.6-3.1, 3.1-3.35, 3.4-3.75, 4.3-4.6 and 4.9-5.6 (all 14H, m), 6.62 (1H, d, J=8.3 Hz), 6.85-7.5 (9H, m), 7.6-7.8 (1H, m)

[1133] The compound of Example 643 1H-NMR (200 MHz, CDCl3) δ ppm: 0.78-1.06, 1.14-2.19, 2.59-3.30, 3.40-4.65 and 4.94-5.16 [all 21H, m, 3.69 (s)], 6.78-7.75 and 8.56-8.70 [all 8H, 7.45 (s)]

[1134] The compound of Example 644 1H-NMR (200 MHz, CDCl3) δ ppm: 0.92 (6H, d, J=6.71 Hz), 1.19-2.32, 2.55-4.62 and 4.95-5.16 (all 12H, m), 6.32-7.95 [all 9H, m, 7.55 (s)]

[1135] The compound of Example 645 1H-NMR (200 MHz, CDCl3) δ ppm: 1.15-2.31, 2.52-4.70 and 4.90-5.15 [all 14H, m, 3.69 (s)], 6.79-7.81 and 8.55-8.72 (all 8H, m)

[1136] The compound of Example 646 1H-NMR (200 MHz, CDCl3) δ ppm: 1.13-2.35, 2.62-4.71 and 4.98-5.19 [all 16H, , 3.70 (s)], 6.81-7.92 (all 7H, m, 7.52 (d, J=2.06 Hz)]

[1137] The compound of Example 649 1H-NMR (200 MHz, DMSO-d6) δ ppm: 0.98-4.60 and 4.78-4.90 (all 13H, m), 6.05-6.21 and 6.40-8.08 (all 7H, m)

[1138] The compound of Example 647 1H-NMR (200 MHz, CDCl3) δ ppm: 1.25-2.32, 2.60-3.31, 3.40-4.68 and 5.05-5.20 [all 18H, m, 3.69 (s)], 6.58-7.81 (8H, m)

[1139] The compound of Example 648 1H-NMR (200 MHz, CDCl3) δ ppm: 1.05-2.32, 2.58-3.90, 4.00-4.68 and 5.00-5.18 [all 18H, m, 3.70 (s)], 6.80-7.64 (7H, m)

[1140] The compound of Example 650 1H-NMR (200 MHz, CDCl3) δ ppm: 2.89 (2H, t, J=6 Hz), 4.35 (2H, t, J=6 Hz), 7.0 (1H, d, J=7 Hz), 7.2-7.7 (10H, m), 7.99 (1H, d, J=2.5 Hz)

[1141] The compound of Example 651 1H-NMR (200 MHz, CDCl3) δ ppm: 1.33 (3H, t, J=7 Hz), 3.44 (2H, dt, J=6.4 Hz, J=2.4 Hz), 3.98 (2H, t, J=6.4 Hz), 4.23 (2H, q, J=7 Hz), 6.41 (1H, t, J=2.4 Hz), 6.86 (1H, d, J=8.6 Hz), 7.0 (1H, dd, J=8.4 Hz, J=2.4 Hz), 7.35-7.70 (10H, m)

[1142] The compound of Example 652

[1143]

1
H-NMR (200 MHz, CDCl3) δ ppm: 1.29 (3H, t, J=7 Hz), 1.8-2.3 (2H, m), 2.6-2.8 (1H, m), 2.8-3.0 (1H, m), 3.3-3.56 (1H, m), 3.85-4.1 (2H, m), 4.22 (2H, q, J=7 Hz), 6.69 (1H, d, J=8.6 Hz), 6.89 (1H, dd, J=8.6 Hz, J=2.4 Hz), 7.2-7.7 (10H, m)

[1144] The compound of Example 653 1H-NMR (200 MHz, CDCl3) δ ppm: 1.1-1.7 (5H, m), 1.7-2.1 (5H, m), 2.4-2.75 (1H, m), 2.85 (2H, t, J=6 Hz), 4.3 (2H, t, J=6 Hz), 7.0 (1H, d, J=8.8 Hz), 7.19-7.27 (3H, m), 7.40-7.45 (2H, m), 7.96 (1H, d, J=2.5 Hz)

[1145] The compound of Example 654 1H-NMR (200 MHz, CDCl3) δ ppm: 2.9 (2H, t, J=6.4 Hz), 3.96 (3H, s), 4.31 (2H, t, J=6.4 Hz), 6.94-7.1 (2H, m), 7.35-7.40 (2H, m), 7.77 (1H, d, J=8.0 (1 H, d, J=2.5 Hz)

[1146] The compound of Example 655 1H-NMR (200 MHz, CDCl3) δ ppm: 1.85-2.05 (1H, m), 2.15-2.35 (1H, m), 2.65 (1H, m), 2.85 (1H, m), 3.35-3.55 (1H, m), 3.85-4.10 (2H, m), 6.70 (1H, d, J=8.6 Hz), 6.90 (1H, dd, J=8.6 Hz, J=2.4 Hz), 7.25-7.65 (10H, m)

[1147] The compound of Example 656 1H-NMR (200 MHz, CDCl3) δ ppm: 1.1-1.55 (5H, m), 1.33 (3H, t, J=7.2 Hz), 1.65-2.0 (5H, m), 2.45-2.65 (1H, m), 3.35-3.5 (2H, m), 3.94 (2H, t, J=6.4 Hz), 4.22 (2H, q, J=7.2 Hz), 6.40 (1H, t, J=2.3 Hz), 6.85 (1H, d, J=8.7 Hz), 7.05 (1H, dd, J=8.7 Hz, J=2.3 Hz), 7.15 (2H, d, J=8.2 Hz), 7.34 (2H, d, J=8.2 Hz), 7.65 (1H, d, J=2.3 Hz)

[1148] The compound of Example 657 1H-NMR (200 MHz, CDCl3) δ ppm: 1.35-1.60 (5H, m), 1.70-2.0 (6H, m, 2.10-2.35 (1H, m), 2.35-2.65 (1H, m), 2.67 (1H, dd, J=16 Hz, J=6 Hz), 2.90 (1H, dd, J=16 Hz, J=6 Hz), 3.35-3.55 (1H, m), 3.85-4.05 (2H, m), 6.70 (1H, d, J=8.7 Hz), 6.89 (1H, dd, J=8.7 Hz, J=2.3 Hz), 7.12 (2H, d, J=8.2 Hz), 7.19 (1H, d, J=2.3 Hz), 7.28 (2H, d, J=8.2 Hz)

[1149] The compound of Example 658 1H-NMR (200 MHz, CDCl3) δ ppm: 1.85-2.10 (1H, m), 2.15-2.35 (1H, m), 2.68 (1H, dd, J=16 Hz, J=8 Hz), 2.87 (1H, dd, J=16 Hz, J=6.2 Hz), 3.3-3.5 (1H, m), 3.75 (3H, S), 3.8-4.15 (2H, m), 6.4-6.55 (1H, m), 6.88 (1H dd, J=8.6 Hz), J=2.3 Hz), 7.20 (1H, d, J=2.3 Hz), 7.54 (2H, d, J=8.9 Hz), 8.16 (2H, d, J=8.9 Hz)

[1150] The compound of Example 659 1H-NMR (200 MHz, CDCl3) δ ppm: 1.85-2.10 (1H, m), 2.20-2.40 (1H, m), 2.71 (1H, dd, J=16 Hz, J=8.4 Hz), 2.94 (1H, dd, J=16 Hz, J=6 Hz), 3.35-3.55 (1H, m), 3.85-4.10 (2H, m), 6.70 (1H, d, J=8.6 Hz), 6.90 (1H, dd, J=8.6 Hz, J=2.3 Hz), 7.21 (1H, d, J=2.3 Hz), 7.35-7.70 (9H, m)

[1151] The compound of Example 660 1H-NMR (200 MHz, CDCl3) δ ppm: 1.80-2.0 (1H, m), 2.10-2.30 (1H, m), 2.62 (1H, dd, J=15.6 Hz, J=8.6 Hz). 2.84 (1H, dd, J=15.6 Hz, J=6 Hz), 3.3-3.5 (1H, m), 3.73 (3H, s), 3.80-4.10 (4H, m), 6.50 (2H, d, J=8.5 Hz), 6.67(1H, d, J=8.5 Hz), 6.89 (1H, dd, J=8.7 Hz, J=2.2 Hz), 7.15-7.35 (3H, m)

[1152] The compound of Example 661 1H-NMR (200 MHz, CDCl3) δ ppm: 1.75-1.95 (1H, m), 2.10-2.30 (1H, m), 3.63 (1H, dd, J=15.6 Hz, J=8.4 Hz), 2.85 (1H, dd, J=15.6 Hz, J=6.2 Hz), 3.3-3.5 (1H, m), 3.74 (3H, s), 3.80-4.05 (2H, m), 4.61 (2H, s), 6.6 (1H, d, J=8.6 Hz), 6.88 (1H, dd, J=8.6 Hz, J=2.2 Hz), 6.95-7.65, 8.36 [all 11H, m, 8.36(s)]

[1153] The compound of Example 662 1H-NMR (200 MHz, CDCl3) δ ppm: 1.80-2.10 (1H, m), 2.15-2.30(1H, m), 2.71 (1H, dd, J=16 Hz, J=8 Hz), 2.90 (1H, dd, J=16 Hz, J=6 Hz), 3.3-3.5 (1H, m), 3.75-4.10 (2H, m), 4.60 (2H, s), 6.59 (1H, d, J=8.6 Hz), 6.88 (1H, dd, J=8.6 Hz, J=2.2 Hz), 6.97 (2H, d, J=7.8 Hz), 6.99-7.10 (1H, m), 7.20 (1H, d, J=2.2 Hz), 7.31-7.39 (4H, m), 7.54 (2H, d, J=8.6 Hz), 8.38 (1H, s)

[1154] The compound of Example 663 1H-NMR (200 MHz, CDCl3) δ ppm: 1.75-1.95 (1H, m), 2.10-2.20 (1H, m), 2.2 (3H, s), 2.60 (1H, dd, J=15.7 Hz, J=8.6 Hz), 2.83 (1H, dd, J=15.7 Hz, J=6 Hz), 3.3-3.4 (1H, m), 3.78 (3H, s), 3.8-4.0 (2H, m), 4.69 (2H, s), 6.60 (1H, d, J=8.7 Hz), 6.87 (2H, dt, J=8.6 Hz, J=2.2 Hz), 6.94-7.01 (1H, m), 7.10-7.50 (5H, m), 7.64 (2H, d, J=8.7 Hz), 7.74 (1H, s), 9.60 (1 H, s)

[1155] The compound of Example 664 1H-NMR (200 MHz, CDCl3) δ ppm: 1.75-2.00 (1H, m), 2.15-2.35 (1H, m), 2.64 (1H, dd, J=15.7 Hz, J=8.6 Hz), 2.86 (1H, dd, J=15.7 Hz, J=6 Hz), 3.3-3.35 (1H, m), 3.75 (3H, s), 3.80-4.00 (2H, m), 4.72 (2H, s), 6.61 (1H, d, J=8.6 Hz), 6.87 (1H, dd, J=8.8 Hz, J=2.2 Hz), 6.93-7.07 (2H, m), 7.17 (1H, d, J=2.2 Hz), 7.25-7.50 (4H, m), 7.58 (2H, d, J=8.6 Hz), 8.78 (1H, s)

[1156] The compound of Example 665 1H-NMR (200 MHz, CDCl3) δ ppm: 1.80-2.05 (1H, m), 2.10-2.30 (1H, m), 2.71 (1H, dd, J=16 Hz, J=8.2 Hz), 2.92 (1H, dd, J=16 Hz, J=6 Hz), 3.30-3.5 (1H, m), 3.75-4.10 (2H, m), 4.65 (2H, s), 6.55-7.65 [all 11H, m, 6.60 (d, J=8.6 Hz), 7.57 (d, J=8.6 Hz)], 8.79 (1H, s)

[1157] The compound of Example 666 1H-NMR (200 MHz, CDCl3) δ ppm: 1.80-2.0 (1H, m), 2.1-2.3 (1H, m), 2.36 (3H, s), 2.63 (1H, dd, J=15.6 Hz, J=8.5 Hz), 2.86 (1H, dd, J=15.6 Hz, J=6 Hz), 3.3-3.5 (1H, m), 3.74 (3H, s), 3.83-3.99 (2H, m), 4.59 (2H, s), 6.60 (1H, d, J=8.6 Hz), 6.78 (2H, d, J=8 Hz), 6.88 (2H, dd, J=8.6 Hz, J=2 Hz), 7.16-7.26 (2H, m) 7.38 (2H, d, J=8.7 Hz), 7.55 (2H, d, J=8.7 Hz), 8.36 (1H, m),

[1158] The compound of Example 667 1H-NMR (200 MHz, CDCl3) δ ppm: 1.8-2.25, 2.65-4.10 (all 10H, m), 4.68 (2H, s), 6.4-7.85 (all 13H, m), 9.48 (1H, s)

[1159] The compound of Example 668 1H-NMR (200 MHz, CDCl3) δ ppm: 1.8-3.0 (all 7H, m), 3.25-3.50 (1H, m), 3.70-4.05 (2H, m), 4.56 (2H, s), 6.60 (1H, d, J=8.5 Hz), 6.75-6.90 (4H, m), 7.18-7.26 (2H, m), 7.35 (2H, d, J=8.6 Hz), 7.52 (2H, d, J=8.7 Hz), 8.4 (1H, s)

[1160] The compound of Example 669 1H-NMR (200 MHz, CDCl3) δ ppm: 0.9-2.25, 2.6-4.1, 4.3-4.75 [all 15H, m, 0.99 (t, J=7.2 Hz)], 6.8-7.5, 7.55-7.65, 8.2-8.5 [all 13H, m, 7.60 (d, J=4 Hz), 8.25 (d, J=4 Hz)]

[1161] The compound of Example 670 1H-NMR (200 MHz, CDCl3) δ ppm: 1.3-2.2, 2.35-2.5, 2.7-3.9 and 4.4-4.65 [all 15H, m, 2.40 (s), 3.73 (s)], 6.55 (0.6H, d, J=8.3 Hz), 6.89 (1.3H, d, J=8.3 Hz), 7.0-7.5 (all 4H, m), 8.35-8.50 (0.8H, m), 8.9-9.05 (0.25H, m)

[1162] The compound of Example 671 1H-NMR (200 MHz, CDCl3) δ ppm: 1.1-2.2, 2.7-3.4, 3.5-3.8 and 4.45-4.65 [all 12H, m, 3.69 (s)], 6.85-7.5 and 8.9-9.1 (all 8H, m)

[1163] The compound of Example 672 1H-NMR (200 MHz, CDCl3) δ ppm: 1.4-2.3, 2.75-3.25 and 4.75-5.05 (all 8H, m), 6.75-7.45 (all 7H, m), 9.55 and 10.03 (all 1H, each s)

[1164] The compound of Example 673 1H-NMR (200 MHz, CDCl3) δ ppm: 1.15-2.2, 2.6-3.85 and 4.4-4.65 [all 15H, m, 2.83 (s)], 6.21 (0.7H, dd, J=8.7 Hz, J=2.5 Hz), 6.51 (0.6H, d, J=2.5 Hz), 6.6-7.4 (all 5.7H, m)

[1165] The compound of Example 674 1H-NMR (200 MHz, CDCl3) δ ppm: 1.0-2.1, 2.7-3.9, 4.4-5.3 [all 17H, m, 1.1 (d, J=6 Hz)], 6.0-6.1 and 6.4-7.6 (all 8H, m)

[1166] The compound of Example 675 1H-NMR (200 MHz, CDCl3) δ ppm: 1.2-2.2, 2.7-4.0 and 4.45-4.7 (all 13H, m), 5.9 and 6.9-7.7 [all 8H, m, 5.9 (s)]

[1167] The compound of Example 676 1H-NMR (200 MHz, CDCl3) δ ppm: 1.2-2.35, 2.75-3.10, 3.10-3.95 and 4.4-4.6 [all 16H, m, 2.79 (s)], 6.3-7.6 (all 7H, m)

[1168] The compound of Example 677 1H-NMR (200 MHz, CDCl3) δ ppm: 1.1-1.25, 1.25-2.2, 2.7-3.95 and 4.45-4.65 (all 22H, m), 6.85-7.8 (all 7H, m), 7.8-8.5 (1H, m)

[1169] The compound of Example 678 1H-NMR (200 MHz, CDCl3) δ ppm: 1.35-2.05, 2.65-4.0 and 4.3-4.65 [all 15H, m, 4.39 (s)], 5.8-6.85 (1H, m), 6.85-8.15 (all 12H, m)

[1170] The compound of Example 679 1H-NMR (200 MHz, CDCl3) δ ppm: 1.04-2.20 [all 7H, m, 1.41 (t, J=7.0 Hz)], 2.32-3.32, 3.33-4.30, 4.43-4.70 and 5.00-5.22 (all 13H, m, 2.51 (s), 3.72 (s)], 6.43-7.67 (11H, m)

[1171] The compound of Example 680 1H-NMR (200 MHz, CDCl3) δ ppm: 1.03 (3H, t, J=7.0 Hz), 0.90-2.30 (6H, m), 2.38-3.30, 3.38-4.36, 4.43-4.70 and 5.04-5.23 [all 13H, m, 2.52 (s), 3.72 (s), 3.93 (t)], 6.43-7.64 (11H, m)

[1172] The compound of Example 683 1H-NMR (200 MHz, CDCl3) δ ppm: 1.24-3.02 (5H, m), 3.04-3.89, 3.90-4.88 and 4.93-5.14 (all 10H, m, 3.71 (s), 3.74 (s), 3.76 (s), 3.82 (s)], 6.49-6.65, 6.71-6.86, 6.94-7.10, 7.11-7.42 and 7.58-7.78 (all 6H, m)

[1173] The compound of Example 684 1H-NMR (200 MHz, CDCl3) δ ppm: 1.12-2.23, 2.24-3.93, 4.01-4.31, 4.43-4.70 and 5.01-5.22 [all 18H, m, 2.37 (s), 2.44 (s), 2.53 (s), 2.57 (s), 3.72 (s)], 6.47-7.59 (11H, m)

[1174] The compound of Example 685 1H-NMR (200 MHz, CDCl3) δ ppm: 1.11-2.26 (4H, m), 2.56-4.32, 4.45-4.73 and 5.00-5.20 [all 8H, m, 3.71 (s)], 6.68-7.81 (12H, m)

[1175] The compound of Example 686 1H-NMR (200 MHz, CDCl3) δ ppm: 1.13-2.37, 2.42-4.39, 4.47-4.75 and 5.04-5.26 [all 15H, m, 2.56 (s), 3.73 (s)], 6.49-7.95 and 8.13-8.49 (all 11H, m)

[1176] The compound of Example 687 1H-NMR (200 MHz, CDCl3) δ ppm: 1.18-2.27 (4H, m), 2.28-4.39, 4.45.4.72 and 5.03-5.27 [all 14H, m, 2.35 (s), 2.41 (s), 2.52 (s), 2.56 (s)], 6.49-7.64 (11H, m)

[1177] The compound of Example 689 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.00-3.76, 4.28-4.55 and 4.81-5.05 [all 15H, m, 2.31 (s), 2.44 (s)], 6.49-7.79 (11H, m), 12.31 (1H, s)

[1178] The compound of Example 690 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.04-2.22 (4H, m), 2.32-3.76, 4.27-4.58 and 4.81-5.08 (all 8H, m), 6.49-8.48 (11H, m), 11.97-12.54 (1H, m)

[1179] The compound of Example 691 1H-NMR (200 MHz, CDCl3) δ ppm: 1.02-3.86, 4.36-4.62 and 5.01-5.30 [all 26H, m, 2.41 (s), 3.74 (s)], 6.36-7.40 (6H, m)

[1180] The compound of Example 692 1H-NMR (200 MHz, CDCl3) δ ppm: 2.20-3.01, 3.32-4.28 and 4.78-5.49 [all 23H, m, 2.35 (s), 2.44 (s), 3.82 (s)], 6.55-7.75 (11H, m)

[1181] The compound of Example 693 1H-NMR (200 MHz, CDCl3) δ ppm: 1.12-2.05 (10H, m), 2.19-2.95, 3.42-4.25 and 4.75-5.39 [all 21H, m, 2.35 (s)], 6.59-7.55 (7H, m)

[1182] The compound of Example 696 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.48 (3H, d, J=6.6 Hz),1.57-2.13 (2H, m), 2.86-3.13 (2H, m), 3.36-3.65 (1H, m), 4.43-4.63 (1H, m), 4.70-4.93 (1H, m), 6.48-8.00 (12H, m), 10.19 and 10.46 (all 1H, s), 12.68 (1H, brs)

[1183] The compound of Example 700 1H-NMR (200 MHz, CDCl3) δ ppm: 1.31 (3H, t, J=7.1 Hz), 1.58 (3H, d, J=6.7 Hz), 1.51-2.33 (2H, m), 2.97-3.23 (2H, m), 3.40-3.70 (1H, m), 3.81-4.18 (2H, m), 4.25 (2H, q, J=7.1 Hz), 4.40-4.91 (1H, m), 4.73 (1H, q, J=6.7 Hz), 6.51-7.65 (12H, m), 8.22 (1H, brs)

[1184] The compound of Example 701 1H-NMR (200 MHz, CDCl3) δ ppm: 1.34 (3H, t, J=7.11 Hz), 2.28-3.00 (2H, m), 3.71-5.12 (all 6H, m), 6.85-7.65 and 7.75-8.45 (all 7H, m)

[1185] The compound of Example 702 1H-NMR (200 MHz, CDCl3) δ ppm: 1.32 (3H, t, J=7.12 Hz), 2.32-2.90 (2H, m), 3.61-4.49 (all 6H, m), 4.65-5.05 (2H, m), 6.10-7.68 (all 7H, m)

[1186] The compound of Example 703 1H-NMR (200 MHz, CDCl3) δ ppm: 1.22-1.43 (3H, m), 1.78-2.38 (2H, m), 2.99-3.24 (2H, m), 3.43-3.66 (1H, m), 3.78-4.39 (4H, m), 4.65-4.89 (1H, m), 6.67 (1H, dt, J=7.6 Hz, J=1.3 Hz), 6.70 (1H, dd, J=8.2 Hz, J=1.3 Hz), 6.89-6.99 (1H, m), 7.05 (1H, dd, J=7.3 Hz, J=1.7 Hz), 7.37 (1H, d, J=8.4 Hz), 7.81 (1H, dd, J=8.4 Hz, J=2.1 Hz), 8.10 (1H, d, J=2.1 Hz)

[1187] The compound of Example 704 1H-NMR (200 MHz, CDCl3) δ ppm: 1.32 (3H, t, J=7.16 Hz), 1.50-1.81 [all 3H, m, 1.59 (d, J=6.71 Hz)], 2.50-2.95 and 3.69-5.15 (all 9H, m), 6.81-8.55 [13H, m, 7.55 (s), 8.26 (s)]

[1188] The compound of Example 705 1H-NMR (200 MHz, CDCl3) δ ppm: 1.41-1.75 [all 3H, m, 1.59 (d, J=6.76 Hz)], 1.75-2.89, 3.60-4.48 and 4.60-5.10 (all 7H, m), 6.79-8.20 and 8.36-8.88 (all 12H, m)

[1189] The compound of Example 706 1H-NMR (200 MHz, CDCl3) δ ppm: 0.72-1.10 (6H, m), 1.33 (3H, t, J=7.13 Hz), 1.80-2.10, 2.55-2.90, 3.69-4.59 and 4.75-5.05 [all 11H, m, 7.29 (q, J=7.13 Hz)], 6.71-7.85, 8.59-8.70 [all 8H, m, 6.63 (s)]

[1190] The compound of Example 707 1H-NMR (200 MHz, CDCl3) δ ppm: 1.33 (3H, t, J=6.17 Hz), 2.31-2.95 and 3.39-5.10 (all 12H, m), 6.72-7.89 (8H, m)

[1191] The compound of Example 708 1H-NMR (200 MHz, CDCl3) δ ppm: 1.34 (3H, t, J=7.15 Hz), 2.55-3.05, 3.70-4.61 and 4.79-5.08 [all 12H, m, 4.29 (q, J=7.15 Hz), 4.46 (t, J=7.88 Hz)], 6.81-7.72 (7H, m)

[1192] The compound of Example 709 1H-NMR (200 MHz, DMSO-d6) δ ppm: 0.89 (6H, d, J=6.69 Hz), 1.70-2.05, 2.30-4.20 and 4.45-4.82 (all 9H, m), 6.85-7.79, 8.10-8.20 and 9.65-9.95 [all 8H, m, 8.14 (s), 9.70 (s)]

[1193] The compound of Example 710 1H-NMR (200 MHz, DMSO-d6) δ ppm: 2.05-5.05 (11H, m), 6.70-8.00 (7H, m)

[1194] The compound of Example 711 1H-NMR (200 MHz, CDCl3) δ ppm: 0.99-1.98, 2.18-3.00 and 3.64-4.01 [all 18H, m, 2.34 (s)], 6.50-7.61 and 8.40-8.73 (all 8H, m)

[1195] The compound of Example 712 1H-NMR (200 MHz, CDCl3) δ ppm: 2.43 (3H, s), 2.62-3;00, 3.71-4.20 and 4.55-5.29 [all 7H, m, 3.82 (s)], 6.62-7.65 and 8.45-8.75 [all 12H, m, 7.42 (d, J=8.45 Hz)]

[1196] The compound of Example 713 1H-NMR (200 MHz, CDCl3) δ ppm: 1.10-3.81 and 4.81-5.35 [all 21H, m, 2.37 (s)], 6.35-7.50 (7H, m)

[1197] The compound of Example 714 1H-NMR (200 MHz, CDCl3) δ ppm: 1.55-4.05 and 4.85-5.25 [all 13H, m, 2.46 (s), 3.81 (s)], 6.40-7.61 (11H, m)

[1198] The compound of Example 715 1H-NMR (200 MHz, CDCl3) δ ppm: 1.04-2.01, 2.18-3.10, 3.56-4.49 and 4.61-5.65 [all 20H, m, 2.35 (s)], 6.51-7.65 (7H, m)

[1199] The compound of Example 716 1H-NMR (200 MHz, CDCl3) δ ppm: 1.34 (3H, t, J=7.08 Hz), 2.15-3.10, 3.61-4.51 and 4.78-5.11 [all 14H, m, 2.44 (s), 3.83 (s)], 6.61-7.58 (11H, m)

[1200] The compound of Example 717 1H-NMR (200 MHz, CDCl3) δ ppm: 1.01-2.97, 3.51-4.28 and 4.75-5.19 [all 20H, m, 2.34 (s)], 6.40-7.70 (8H, m)

[1201] The compound of Example 718 1H-NMR (200 MHz, CDCl3) δ ppm: 2.29-2.94, 3.56-4.29 and 4.75-5.08 [all 12H, m, 2.43 (s), 3.82 (s)], 6.59-7.65 (7H, m), 8.55-9.07 (1H, m)

[1202] The compound of Example 719 1H-NMR (200 MHz, CDCl3) δ ppm: 1.53 (9H, s), 2.51-2.96, 3.72-4.31 and 4.51-5.18 (all 6H, m), 6.85-7.62 and 7.78-8.41 (all 7H, m)

Example 721

[1203] To dimethylsulfide (170 ml) is added dropwise with stirring aluminum chloride (23.6 g) under ice-cooling, and further thereto is added dropwise a solution of 5-methoxycarbonylmethyl-1-[4-(2-phenoxyacetylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (16.76 g) in dichloromethane (150 ml), and the mixture is stirred at room temperature for two hours. The reaction mixture is poured into a mixture of conc. hydrochloric acid and crashed ice, and the mixture is extracted with dichloromethane. The organic layer is washed with water, dried over magnesium sulfate, and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; dichloromethane:methanol=30:1) to give 5-carboxymethyl-1-[4-(2-phenoxyacetylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (13.67 g) as white powder.

[1204] M.p. 102-106° C.

Example 722

[1205] 7-Chloro-1-[2-methyl-4-(2-acetylacetylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.48 g) is dissolved in tetrahydrofuran (7 ml), and thereto is added a 5N aqueous sodium hydroxide solution (0.5 ml), and the mixture is stirred at room temperature for two hours. The reaction solution is neutralized with a 2N hydrochloric acid, and extracted with ethyl acetate. The extract is dried over magnesium sulfate, filtered, and concentrated. To the resulting residue is added n-hexane/ethyl acetate (1:1), and the mixture is washed, filtered, and the obtained powder is dried to give 7-chloro-1-[2-methyl-4-(2-hydroxyacetylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.38 g) as white powder.

[1206] M.p. 194-195° C.

Example 723

[1207] 1-[2-Methyl-4-(2-chloroacetylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.8 g) is dissolved in dimethylformamide (5 ml), and thereto are added potassium carbonate (0.47 g), sodium iodide (0.51 g) and 5,6,7,8-tetrahydro-1-naphthol (0.40 g), and the mixture is stirred at 60° for three hours. To the reaction solution is added ethyl acetate, and the mixture is washed with a saturated aqueous potassium hydrogen sulfate solution and a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated. The resulting residue is allowed to stand for one day, washed with dichloromethane, filtered, and dried to give 1-{2-methyl-4-[2-(5-tetrahydronaphthyloxy)acetylamino]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine (0.72 g) as white powder.

[1208] M.p. 230-232° C. (decomposed)

[1209] The suitable starting compounds are treated in the same manner as in Example 723 to give the compounds of Examples 55-58, 147, 148, 150-156, 158-162, 165-166, 160, 170, 176-179, 186-196, 198, 200-207, 212, 213, 215, 217, 222-224, 228-232, 338-346, 355-358, 363, 399-402, 445-448, 583, 593, 598, 661-669, 696-700 and 704-705.

Example 724

[1210] A mixture of 1-(4-amino-2-chlorobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (1 g), triphosgen (0.3 g) and o-dichlorobenzene (10 ml) is heated with stirring at 130-140° C. for four hours. To the mixture is added triethylamine (0.8 ml), and the mixture is stirred for 0.5 hour, and thereto is further added triethylamine (0.8 ml), and the mixture is stirred for 0.5 hour. To the mixture is added 1,2,3,4-tetrahydroisoquinoline (0.38 ml), and the mixture is heated with stirring at 80° C. for one hour. The mixture is diluted with dichloromethane, and washed with water and a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and evaporated to remove the solvent to give an oily residue (2.9 g). The residue is purified by silica gel column chromatography (solvent; ethyl acetate:n-hexane=1:1) to give 1-[4-(2-tetrahydroisoquinolylcarbonylamino)-2-chlorobenzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.47 g) as colorless amorphous.

[1211]

1
H-NMR (200 MHz, CDCl3) δ ppm: 1.35-2.15, 2.70-3.10 and 4.80-5.00 (all 10H, m), 3.66 and 3.76 (all 2H, each t, J=5.8 Hz), 4.60 and 4.71 (all 2H, each s), 6.70-7.50 (12H, m)

Example 725

[1212] To a solution of 1-(4-amino-2-chlorobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (0.8 g) in o-dichlorobenzene (5 ml) is added triphosgen (0.26 g), and the mixture is stirred at 120° C. for three hours. To the mixture is added triethylamine (0.27 g), and the mixture is stirred at 120° C. for two hours. To the mixture is added (4-pyridyl)methanol (0.29 g), and the mixture is stirred at 120° C. for two hours. To the reaction solution is added ethyl acetate, and the mixture is washed with water, and the organic layer is dried over magnesium sulfate, filtered, and evaporated to remove the solvent. The resulting residue is purified by silica gel column chromatography (solvent; ethyl acetate:n-hexane=1:5→dichloromethane:methanol=25:1), and the residue is washed with methanol/diethyl ether to give 1-{4-[(4-pyridyl)methoxycarbonylamino]-2-chlorobenzoyl}-2,3,4,5-tetrahydro-1H-benzazepine (0.45 g) as white powder.

[1213] M.p. 181-184° C.

Example 726

[1214] To chloroform (5 ml) is added triphosgen (0.72 g), and thereto is added with stirring 2-phenoxyethanol (1.0 g) under ice-cooling, during which the temperature of the reaction solution is kept at below 10° C., and the mixture is stirred at 0° C. for one hour. To the reaction solution are added with stirring dropwise 1-(4-amino-2-chlorobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (1.9 g) and a solution of piperidine (2.5 g) in chloroform (30 ml) under ice-cooling. The mixture is stirred at room temperature for three hours, washed with a saturated aqueous potassium hydrogen sulfate solution, distilled water and a saturated aqueous sodium hydrogen carbonate solution, and dried over magnesium sulfate, filtered, and evaporated to remove the solvent. The residue is recrystallized from diethyl ether to give 1-[4-(2-phenoxyethoxy-carbonylamino)-2-chlorobenzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (1.3 g) as white powder.

[1215] M.p. 144-146° C.

[1216] The suitable starting compounds are treated in the same manner as in Examples 725 and 726 to give the compounds of Examples 157, 167, 197,199, 214, 233, 234, 406, 407, 420, 538, 540, 549, 550, 552, 556, 557, 559, 568, 587, 588, 596, 604, 643, 645, 647, 695, 706, 707 and 709.

Example 727

[1217] A mixture of 5-ethoxycarbonylmethyl-1-[4-(2-chloroethoxycarbonylamino)-2-chlorobenzoyl]-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine (0.9 g), potassium carbonate (0.40 g) and sodium iodide (0.43 g) in dimethylformamide (15 ml) is stirred at 8° C. for 8 hours. To the reaction solution is added ethyl acetate, and the mixture is washed with water, and the organic layer is dried over magnesium sulfate, filtered, and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; dichloromethane:methanol=30:1) to give 5-ethoxycarbonylmethyl-1-[4-(2-oxotetra-hydrooxazol-3-yl)-2-chlorobenzoyl]-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine (0.65 g) as colorless amorphous.

[1218]

1
H-NMR (200 MHz, CDCl3) δ ppm: 1.34 (3H, t, J=7.15 Hz), 2.55-3.05, 3.70-4.61 and 4.79-5.08 [all 12H, m, 4.29 (q, J=7.15Hz, 4.46 (t, J=7.88 Hz)], 6.81-7.72 (7H, m)

[1219] The suitable starting compounds are treated in the same manner as in Example 727 to give the compounds of Examples 511, 594, 646, 649, 694 and 710.

Example 728

[1220] To a mixture of 1-[4-(1-piperazinyl)-2-chlorobenzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.25 g), 37% formaldehyde (0.45 g) and sodium tetrahydro-1H-benzazepine (0.25 g), 37% formaldehyde (0.45 g) and sodium (0.12 g) under ice-cooling, and the mixture is stirred at room temperature for one hour. To the reaction solution is added ethyl acetate, and the mixture is washed with a 2N aqueous sodium hydroxide solution and distilled water. The organic layer is dried over magnesium sulfate, filtered, and concentrated, and the resulting residue is purified by silica gel column chromatography (solvent; dichloromethane:methanol=10:1) to give 1-[4-(4-methyl-1-piperazinyl)-2-chlorobenzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.10 g) as white powder.

[1221] M.p. 138-140° C.

[1222] The suitable starting compounds are treated in the same manner in Example 728 to give the compounds of Examples 416, 417, 457, 515, 523, 524, 677 and 678.

Example 729

[1223] 1-[4-Nitro-2-chlorobenzoyl]-1,5-benzodiazepine (5 g) and ethyl bromoacetate (16.7 ml) are dissolved in acetonitrile (100 ml), and thereto is added dropwise 1,8-diazabicyclo[5.4.0]-7-undecene (11.3 ml). The mixture is refluxed for two days, concentrated, and thereto are added water and chloroform, and extracted. The extract is dried over sodium carbonate, and purified by silica gel column chromatography (solvent; n-hexane:ethyl acetate=4:1→1:1) to give 1-(4-nitro-2-chlorobenzoyl)-5-ethoxycarbonylmethyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine (4.4 g) as pale yellow oil.

[1224]

1
H-NMR (200 MHz, CDCl3) δ ppm: 1.22-1.43 (3H, m), 1.78-2.38 (2H, m), 2.99-3.24 (2H, m), 3.43-3.66 (1H, m), 3.78-4.39 (4H, m), 4.65-4.89 (1H, m), 6.67 (1H, dt, J=7.6 Hz, J=1.3 Hz), 6.70 (1H, dd, J=8.2 Hz, J=1.3 Hz), 6.89-6.99 (1H, m), 7.05 (1H, dd, J=7.3 Hz, J=1.7 Hz), 7.37 (1H, d, J=8.4 Hz), 7.81 (1H, dd, J=8.4 Hz, J=2.1 Hz), 8.10 (1H, d, J=2.1 Hz)

[1225] The suitable starting compounds are treated in the same manner as in Example 729 to give the compounds of Examples 692-702, 704-710 and 715-720.

Example 730

[1226] 5-Cyanomethyl-1-(4-phenyl-2-chlorobenzoyl)-2,3,4,5-tetrahyclro-1H-benzazepine (1 g), ammonium chloride (0.4 g) and sodium azide (0.48 g) are suspended in dimethylformamide (10 ml), and the mixture is heated at 110-120° C. for 16 hours. To the mixture are added ammonium chloride (0.4 g) and sodium azide (0.48 g), and the mixture is heated for 16 hours. The mixture is evaporated to remove dimethylformamide, and the resultant is acidified with a 1N hydrochloric acid. The mixture is extracted with chloroform, and the organic layer is washed with water, dried over magnesium sulfate, and concentrated.

[1227] The residue is purified by silica gel column chromatography (solvent; dichloromethane→dichloromethane:methanol=20:1), and the resulting oily product is crystallized from diethyl ether to give 5-(5-tetrazolyl)methyl-1-(4-phenyl-2-chlorobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (0.9 g) as white powder.

[1228] M.p. 191-194° C.

[1229] The suitable starting compounds are treated in the same manner as in Examples 1 and 2 to give the following compounds.

1226

Example 731Structure:

1227

X: —CH2—R1: H

1228

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 732Structure:

1229

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Methanol/diethyl etherM.p. 136-138° C.Form: FreeExample 733Structure:

1230

X: —CH2—R1: H

1231

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 734Structure:

1232

X: —CH2—R1: H

1233

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 735Structure:

1234

X: —CH2—R1: H

1235

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 736Structure:

1236

X: —CH2—R1: HR2: HR3: HCrystalline form: Colorless amorphousForm: FreeExample 737Structure:

1237

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderM.p.: 196-198° C.Form: FreeExample 738Structure:

1238

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Diethyl ether/n-hexaneM.p. 124-126° C.Form: FreeExample 739Structure:

1239

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderSolvent for recrystallization: MethanolM.p. 160-162° C.Form: FreeExample 740Structure:

1240

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Colorless amorphousForm: FreeExample 741Structure:

1241

X: —CH2—R1: H

1242

R3: HCrystalline form: Colorless amorphousForm: FreeExample 742Structure:

1243

X: —CH2—R1: H

1244

R3: HCrystalline form: Colorless amorphousForm: FreeExample 743Structure:

1245

X: —CH2—R1: H

1246

R3: HCrystalline form: Colorless amorphousForm: FreeExample 744Structure:

1247

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Diethyl ether/n-hexaneForm: FreeExample 745Structure:

1248

X: —CH2—R1: H

1249

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 746Structure:

1250

X: —CH2—R1: H

1251

R3: HCrystalline form: White powderSolvent for recrystallization: n-Hexane/ethyl acetateM.p. 162-164° C.Form: FreeExample 747Structure:

1252

X: —CH2—R1: H

1253

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 748Structure:

1254

X: —CH2—R1: H

1255

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 749Structure:

1256

X: —CH2—R1: 7-Cl

1257

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 750Structure:

1258

X: —CH2—R1: 7-Cl

1259

R3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherM.p. 118-119° C.Form: FreeExample 751Structure:

1260

X: —CH2—R1: H

1261

R3: HCrystalline form: Colorless amorphousForm: FreeExample 752Structure:

1262

X: —CH2—R1: H

1263

R3: HCrystalline form: Colorless amorphousForm: FreeExample 753Structure:

1264

X: —CH2—R1: H

1265

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 754Structure:

1266

X: —CH2—R1: H

1267

R3: HCrystalline form: Colorless amorphousForm: FreeExample 755Structure:

1268

X: —CH2—R1: H

1269

R3: HCrystalline form: Colorless amorphousForm: FreeExample 756Structure:

1270

X: —CH2—R1: H

1271

R3: HCrystalline form: Colorless amorphousForm: DihydrochlorideExample 757Structure:

1272

X: —CH2—R1: H

1273

R3: HCrystalline form: White powderSolvent for recrystallization: EthanolM.p. 201.5-204° C.Form: HydrochlorideExample 758Structure:

1274

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderM.p. 120-122° C.Form: FreeExample 759Structure:

1275

X: —CH2—R1: HR2:HR3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 760Structure:

1276

X: —CH2—R1: H

1277

R3: HCrystalline form: Colorless amorphousForm: FreeExample 761Structure:

1278

X: —CH2—R1: H

1279

R3: HCrystalline form: Colorless amorphousForm: FreeExample 762Structure:

1280

X: —CH2—R1: 7-Cl

1281

R3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherM.p. 147-148° C.Form: FreeExample 763Structure:

1282

X: —CH2—R1: 7-Cl

1283

R3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherM.p. 178-179° C.Form: FreeExample 764Structure:

1284

X: —CH2—R1: H

1285

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 765Structure:

1286

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Colorless flakesSolvent for recrystallization: Methanol/chloroform/diethyl etherM.p. >300° C.Form: FreeExample 766Structure:

1287

X: —CH2—R1: H

1288

R3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherForm: FreeExample 767Structure:

1289

X: —CH2—R1: H

1290

R3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherForm: FreeExample 768Structure:

1291

X: —CH2—R1: H

1292

R3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherForm: FreeExample 769Structure:

1293

X: —CH2—R1: H

1294

R3: HCrystalline form: Colorless amorphousForm: FreeExample 770Structure:

1295

X: —CH2—R1: 7-Cl

1296

R3: HCrystalline form: Colorless amorphousForm: FreeExample 771Structure:

1297

X: —CH2—R1: H

1298

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 772Structure:

1299

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Yellow powderM.p. 130-133° C.Form: FreeExample 773Structure:

1300

X: —CH2—R1: H

1301

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 774Structure:

1302

X: —CH2—R1: H

1303

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 775Structure:

1304

X: —CH2—R1: H

1305

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 776Structure:

1306

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderSolvent for recrystallization: Ethyl acetateM.p. 174.5-175.5° C.Form: FreeExample 777Structure:

1307

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Brown amorphousForm: FreeExample 778Structure:

1308

X: —CH2—R1: 7-Cl

1309

R3: HCrystalline form: Colorless amorphousForm: FreeExample 779Structure:

1310

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Pale yellow powderSolvent for recrystallization: Chloroform/diethyl etherForm: FreeExample 780Structure:

1311

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Yellow powderSolvent for recrystallization: Chloroform/diethyl etherForm: FreeExample 781Structure:

1312

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Pale yellow powderSolvent for recrystallization: Chloroform/diethyl etherForm: FreeExample 782Structure:

1313

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderM.p. 123-125° C.Form: FreeExample 783Structure:

1314

X: —CH2—R1: 7-Cl

1315

R3: HCrystalline form: Colorless amorphousForm: FreeExample 784Structure:

1316

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Colorless amorphousForm: FreeExample 785Structure:

1317

X: —CH2—R1: 7-Cl

1318

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 786Structure:

1319

X: —CH2—R1: 7-Cl

1320

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 787Structure:

1321

X: —CH2—R1: 7-Cl

1322

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 788Structure:

1323

X: —CH2—R1: 7-Cl

1324

R3: HCrystalline form: Colorless amorphousForm: FreeExample 789Structure:

1325

X: —CH2—R1: 7-Cl

1326

R3: HCrystalline form: Colorless amorphousForm: FreeExample 790Structure:

1327

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Yellow amorphousForm: FreeExample 791Structure:

1328

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Yellow powderM.p. 135-139° C.Form: FreeExample 792Structure:

1329

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Colorless amorphousForm: FreeExample 793Structure:

1330

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: White powderM.p. 123-125° C.Form: FreeExample 794Structure:

1331

X: —CH2—R1: H

1332

R3: HCrystalline form: Colorless amorphousForm: FreeExample 795Structure:

1333

X: —CH2—R1: H

1334

R3: HCrystalline form: Colorless amorphousForm: FreeExample 796Structure:

1335

X: —CH2—R1: 7-Cl

1336

R3: HCrystalline form: Pale yellow amorphousForm: FreeExample 797Structure:

1337

X: —CH2—R1: 7-Cl

1338

R3: HCrystalline form: Colorless amorphousForm: FreeExample 798Structure:

1339

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Pale yellow powderSolvent for recrystallization: Chloroform/diethyl etherForm: FreeExample 799Structure:

1340

X: —CH2—R1: 7-ClR2: HR3: HCrystalline form: Pale yellow powderSolvent for recrystallization: Chloroform/diethyl etherForm: FreeExample 800Structure:

1341

X: —CH2—R1: 7-ClR2: HR3: HExample 801Structure:

1342

X: —CH2—R1: HR2: —CH2CONH(CH2)2N(C2H5)2R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 802Structure:

1343

X: —CH2—R1: 7-Cl

1344

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 803Structure:

1345

X: —CH2—R1: 7-ClR2: —CH2CONH(CH2)2N(C2H5)2R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 804Structure:

1346

X: —CH2—R1: 7-Cl

1347

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 805Structure:

1348

X: —CH2—R1: 7-ClR2: —CH2CONH(CH2)2N(C2H5)2R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 806Structure:

1349

X: —CH2—R1: 7-Cl

1350

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 807Structure:

1351

X: —CH2—R1: 7-ClR2: —CH2CONH(CH2)2N(C2H5)2R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 808Structure:

1352

X: —CH2—R1: 7-Cl

1353

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 809Structure:

1354

X: —CH2—R1: 7-ClR2: —CH2CONH(CH2)2N(C2H5)2R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 810Structure:

1355

X: —CH2—R1: 7-Cl

1356

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 811Structure:

1357

X: —CH2—R1: 7-ClR2: —CH2CONH(CH2)2N(C2H5)2R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 812Structure:

1358

X: —CH2—R1: 7-Cl

1359

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 813Structure:

1360

X: —CH2—R1: 7-Cl

1361

R3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 814Structure:

1362

X: —CH2—R1: HR2: —CH2CO2CH3R3: HCrystalline form: White powderSolvent for recrystallization: Chloroform/diethyl etherForm: HydrochlorideExample 815Structure:

1363

X: —CH2—R1: HR2: —CH2CO2HR3: HForm: HydrochlorideExample 816Structure:

1364

X: —CH2—R1: HR2: —CH2CO2CH3R3: HCrystalline form: White powderSolvent for recrystallization: Ethyl acetate/n-hexaneForm: FreeExample 817Structure:

1365

X: —CH2—R1: HR2: —CH2CO2HR3: HCrystalline form: Colorless amorphousForm: FreeExample 818Structure:

1366

X: —CH2—R1: HR2: —CH2CO2CH3R3: HCrystalline form: Yellow viscous oilForm: FreeExample 819Structure:

1367

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 820Structure:

1368

X: —CH2—R1: HR2: —CH2CO2CH3R3: HCrystalline form: Pale yellow oilForm: FreeExample 821Structure:

1369

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 822Structure:

1370

X: —CH2—R1: HR2: —CH2CO2CH3R3: HCrystalline form: Pale yellow oilForm: FreeExample 823Structure:

1371

X: —CH2—R1: HR2: —CH2CO2HR3: HCrystalline form: Pale yellow amorphousForm: FreeExample 824Structure:

1372

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 825Structure:

1373

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 826Structure:

1374

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: HydrochlorideExample 827Structure:

1375

X: —CH2—R1: HR2: —CH2CNR3: HCrystalline form: White powderForm: FreeExample 828Structure:

1376

X: —CH2—R1: HR2: —CH2CO2CH3R3: HCrystalline form: White powderForm: FreeExample 829Structure:

1377

X: —CH2—R1: HR2: HR3: HCrystalline form: Pale yellow powderForm: FreeExample 830Structure:

1378

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: White powderM.p. 170° C.Form: FreeExample 831Structure:

1379

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderM.p. 177-178° C.Form: FreeExample 832Structure:

1380

X: —CH2—R1: HR2: —CH2COOCH3R3: HCrystalline form: White powderSolvent for recrystallization: Ethyl acetate/n-hexaneM.p. 87-89° C.Form: FreeExample 833Structure:

1381

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: Slightly yellow amorphousForm: FreeExample 834Structure:

1382

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 835Structure:

1383

X: —CH2—R1: HR2: HR3: HCrystalline form: White powderForm: FreeExample 836Structure:

1384

X: —CH2—R1: HR2: —CH2CO2CH3R3: HCrystalline form: Yellow oilForm: FreeExample 837Structure:

1385

X: —CH2—R1: HR2: —CH2CO2CH3R3: HCrystalline form: White powderSolvent for recrystallization: Ethyl acetate/n-hexaneM.p. 99-101° C.Form: FreeExample 838Structure:

1386

X: —CH2—R1: HR2: —CH2CO2HR3: HCrystalline form: Colorless amorphousForm: FreeExample 839Structure:

1387

X: —CH2—R1: HR2: —CH2CO2HR3: HCrystalline form: Colorless amorphousForm: FreeExample 840Structure:

1388

X: —CH2—R1: HR2: —CH2CO2HR3: HCrystalline form: Colorless amorphousForm: FreeExample 841Structure:

1389

X: —CH2—R1: HR2: —CH2COOCH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 842Structure:

1390

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: Pale yellow powderForm: FreeExample 843Structure:

1391

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: White powderForm: FreeExample 844Structure:

1392

X: —CH2—R1: H

1393

R3: HCrystalline form: Colorless amorphousForm: FreeExample 845Structure:

1394

X: —CH2—R1: H

1395

R3: HCrystalline form: Colorless amorphousForm: FreeExample 846Structure:

1396

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: White powderSolvent for recrystallization: AcetoneM.p. 185-187° C.Form: FreeExample 847Structure:

1397

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: White powderSolvent for recrystallization: Ethyl/acetate/n-hexaneM.p. 148.5-150.5° C.Form: FreeExample 848Structure:

1398

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: White powderSolvent for recrystallization: Ethyl acetate/n-hexaneM.p. 160-162° C.Form: FreeExample 849Structure:

1399

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 850Structure:

1400

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Yellow oilForm: FreeExample 851Structure:

1401

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Slightly yellow amorphousForm: FreeExample 852Structure:

1402

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 853Structure:

1403

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 854Structure:

1404

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 855Structure:

1405

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 856Structure:

1406

X: —CH2—R1: 7-ClR2: —CH2CO2HR3: HCrystalline form: Colorless amorphousForm: FreeExample 857Structure:

1407

X: —CH2—R1: 7-ClR2: —CH2CO2HR3: HCrystalline form: Colorless amorphousForm: FreeExample 858Structure:

1408

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 859Structure:

1409

X: —CH2—R1: 7-ClR2: —CH2CO2HR3: HCrystalline form: Colorless amorphousForm: FreeExample 860Structure:

1410

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 861Structure:

1411

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 862Structure:

1412

X: —CH2—R1: 7-ClR2: —CH2CO2CH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 863Structure:

1413

X: —CH2—R1: 7-ClR2: —CH2CO2HR3: HCrystalline form: White powderForm: FreeExample 864Structure:

1414

X: —CH2—R1: 7-ClR2: —CH2COOHR3: HCrystalline form: White powderForm: FreeExample 865Structure:

1415

X: —CH2—R1: HR2: —CH2COOCH3R3: HCrystalline form: Colorless amorphousForm: FreeExample 866Structure:

1416

X: —CH2—R1: HR2: —CH2COOHR3: HCrystalline form: Colorless amorphousForm: FreeExample 867Structure:

1417

X: —CH2—R1: HR2: —CH2CO2CH3R3: HCrystalline form: White powderSolvent for recrystallization: Diethyl etherForm: Free

[1230] The suitable starting compounds are treated in the same manner as in Examples 1 and 2 to give the following compounds.

1418

Example 868Structure:

1419

1420

R1: HR2: HR3: HCrystalline form: Colorless amorphousForm: FreeExample 869Structure:

1421

1422

R1: HR2: HR3: HCrystalline form: Colorless amorphousForm: FreeExample 870Structure:

1423

1424

R1: HR2 and R3: ═OCrystalline form: Colorless amorphousForm: FreeExample 871Structure:

1425

1426

R1: HR2 and R3: ═OCrystalline form: Colorless amorphousForm: FreeExample 872Structure:

1427

1428

R1: HR2 and R3: ═OCrystalline form: White powderM.p. 168-171° C.Form: FreeExample 873Structure:

1429

1430

R1: HR2: HR3: HCrystalline form: Brown amorphousForm: FreeExample 874Structure:

1431

1432

R1: HR2: HR3: HCrystalline form: Brown amorphousForm: FreeExample 875Structure:

1433

1434

R1: HR2: HR3: HCrystalline form: White powderForm: FreeExample 876Structure:

1435

1436

R1: HR2: HR3: HCrystalline form: Colorless amorphousForm: FreeExample 877Structure:

1437

1438

R1: HR2 and R3: ═OCrystalline form: Yellow amorphousForm: FreeExample 878Structure:

1439

1440

R1: HR2 and R3: ═OCrystalline form: Yellow amorphousForm: FreeExample 879Structure:

1441

1442

R1: HR2 and R3: ═OCrystalline form: Brown amorphousForm: FreeExample 880Structure:

1443

Y: ═NHR1: HR2 and R3: ═OCrystalline form: White powderForm: FreeExample 881Structure:

1444

1445

R1: HR2 and R3: ═OCrystalline form: Brown oilForm: FreeExample 882Structure:

1446

1447

R1: HR2 and R3: ═OCrystalline form: White powderForm: FreeExample 883Structure:

1448

Y: ═NHR1: HR2 and R3: ═OCrystalline form: Brown amorphousForm: FreeExample 884Structure:

1449

1450

R1: HR2 and R3: ═OCrystalline form: Brown amorphousForm: FreeExample 885Structure:

1451

1452

R1: HR2 and R3: ═OCrystalline form: Brown powderForm: Free

[1231] The data of NMR analysis of the compounds of the above Examples are as follows.

[1232] NMR analysis:

[1233] The compound of Example 741 1H-NMR (200 MHz, CDCl3) δ ppm: 1.08-1.88 [9H, m, (1.22,1.35, each 3H, each d, J=6.0 Hz)], 1.88-2.61 [11H, m, (2.33, 2.43 each s)], 2.61-4.04, 4.31-4.70, 4.98-5.19 (total 10H, m), 6.12-7.43 (7H, m)

[1234] The compound of Example 742 1H-NMR (200 MHz, CDCl3) δ ppm: 1.10-2.59 [15H, m, (2.33, 2.45, each s)], 2.59-3.09 (2H, m), 3.09-4.01, 4.43-4.64 (total 6H, m), 4.93, 5.09 (total 2H, each s), 6.24-7.51 (12H, m)

[1235] The compound of Example 743 1H-NMR (200 MHz, CDCl3) δ ppm: 1.08-2.61 [15H, m, 2.34 (s)], 2.61-3.02 (2H, m), 3.02-4.11, 4.43-4.64, 4.90-5.12 (total 6H, m), 5.30 (1H, s), 6.00-7.45 (7H, m)

[1236] The compound of Example 754 1H-NMR (200 MHz, CDCl3) δ ppm: 0.82-1.14 [6H, m, 0.95,1.04, (each d, J=6.7 Hz)], 1.15-1.93 (1H, m), 1.95-2.59 [14H, m, 2.33, 4.45, (each s)], 2.59-4.02, 4.45-4.67, 4.98-5.17 (total 11H, m), 6.12-7.46 (7H, m)

[1237] The compound of Example 755 1H-NMR (200 MHz, CDCl3) δ ppm: 0.92, 0.99 (total 6H, each t, J=7.3 Hz), 1.19-2.59 [18H, m, 2.33, 2.44, (each s)], 2.59-4.09, 4.41-4.65, 4.95-5.18 [total 11H, m, 3.83, 3.98, (each t, J=6.5 Hz)], 6.11-7.45 (7H, m)

[1238] The compound of Example 760 1H-NMR (200 MHz, CDCl3) δ ppm: 0.50, 0.95 (total 6H, each d, J=6.5 Hz), 1.01-1.32 [7H, m, 1.04 (3H, d, J=6.7 Hz)], 1.48-3.18 [10H, m, 2.49 (s)], 3.30-4.65, 5.46-5.72 [total 5H, m, (3.75, d, J=6.5 Hz)], 6.40-7.39 (8H, m)

[1239] The compound of Example 761 1H-NMR (200 MHz, CDCl3) δ ppm: 0.50 (3H, d, J=6.5 Hz), 0.85-1.29 [7H, m, 0.95 (3H, d, J=6.5 Hz), 0.99, 1.16 (total 3H, each t, J=5.5 Hz)], 1.35-2.18 (10H, m), 2.19-2.58 [5H, m, 2.49 (s)], 2.58-2.78, 2.89-3.18 (total 2H, m), 3.30-4.65, 5.41-5.67 (total 6H, m), 6.81-7.40 (8H, m)

[1240] The compound of Example 816 1H-NMR (200 MHz, CDCl3) δ ppm: 1.15-2.21 (4H, m), 2.33-2.55, 3.09-3.87, 4.39-4.62 [total 11 H, m, (2.45, 3.69 each s)], 2.60-3.05 (2H, m), 4.81-5.19 [2H, m, 4.93, 5.09 (each s)], 6.25-7.53 (12H, m)

[1241] The compound of Example 817 1H-NMR (200 MHz, CDCl3) δ ppm: 1.15-2.19 (4H, m), 2.44,2.47 (total 3H, each s), 2.11-3.08 (2H, m), 3.08-3.90, 4.39-4.62, 4.79-5.31 [total 7H, 4.89, 5.06 (total 2H, eash s)], 6.25-7.52 (12H, m)

[1242] The compound of Example 818 1H-NMR (200 MHz, CDCl3) δ ppm: 1.12-2.17 [10H, m, 1.24,1.35, (each d, J=6.0 Hz)], 2.32-2.59 [3H, m, 2.43 (s)], 2.61-3.32 (3H, m), 3.41-3.92 [6H, m, 3.70 (s)], 4.29-4.63, 5.01-5.22 (total 2H, m), 6.18-7.42 (7H, m)

[1243] The compound of Example 819 1H-NMR (200 MHz, CDCl3) δ ppm: 1.09-2.22 [10H, m, 1.22, 1.35 (each d, J=6.0 Hz)], 2.30-2.58 [3H, m, 2.43, 2.47 (each s)], 2.11-4.01 (4H, m), 4.28-4.70, 4.99-5.22 (total 2H, m), 6.13-7.48 (8H, m)

[1244] The compound of Example 838 1H-NMR (200 MHz, CDCl3) δ ppm: 0.96, 1.04 (total 6H, each d, J=6.7 Hz), 1.18-2.20 (4H, m), 2.44, 2.48 (total 3H, each s), 2.61-3.31, 3.39-4.16, 5.02-5.27 (total 8H, m), 6.19-7.42 (8H, m)

[1245] The compound of Example 839 1H-NMR (200 MHz, CDCl3) δ ppm: 0.92, 0.99 (total 3H, each t, J=7.2 Hz), 1.15-2.22 (8H, m), 2.43, 2.47 (total 3H, each s), 2.62-3.31, 3.36-4.09, 4.38-4.65, 5.01-5.23 (total 7H, m, (3.82, 3.97, each t, J=6.5 Hz)), 6.17-7.41 (8H, m)

[1246] The compound of Example 765 1H-NMR (200 MHz, CDCl3+DMSO-d6) δ ppm: 1.2-2.3 (4H, m), 2.5-3.4, 4.7-5.1, 5.3-5.6 (total 4H, each m), 6.5-7.5 (9H, m), 7.60 (1H, dd, J=7.5 Hz, 7.5 Hz), 7.95 (1H, d, J=7.5 Hz), 11.43 (1H, s)

[1247] The compound of Example 731 1H-NMR (200 MHz, CDCl3) δ ppm: 1.25-4.30, 4.6-4.85 [total 27H, m, 2.49 (s), 2.84 (s), 2.94 (s)], 6.85-8.0 (total 7H, m)

[1248] The compound of Example 733 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.1-2.1, 2.4-4.1, 4.1-4.7 (total 24H, m), 6.7-7.8, 7.8-8.0, 8.35-8.7 (total 7H, m), 11.1-11.7 (1H, m)

[1249] The compound of Example 734 1H-NMR (200 MHz, DMSO-d6) δ ppm: 0.81-2.20, 2.6-4.0, 4.2-4.6 (total 33H, m), 6.8-8.0 (total 7H, m), 10.8-11.3 (1H, m)

[1250] The compound of Example 735 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.1-2.2, 2.6-4.1, 4.3-4.6 (total 26H, m), 6.8-7.9 [total 12H, m, 7.63 (s), 7.93 (s)], 10.8-11.4 (1H, m)

[1251] The compound of Example 736 1H-NMR (200 MHz, CDCl3) δ ppm: 0.99-2.20, 2.63-3.91, 4.81-5.08 [total 23H, m,1.12 (d, J=6.77 Hz)], 6.48 (1H, dd, J=8.6 Hz, J=8.5 Hz), 6.71-7.48 (6H, m)

[1252] The compound of Example 740 1H-NMR (200 MHz, CDCl3) δ ppm: 1.35-1.80,1.80-2.25, 2.35-2.60, 2.60-3.15, 3.25-3.55, 4.35-4.65, 4.85-5.05 [total 15H, m, 2.46 (s), 4.43 (s), 4.48 (s)]6.52-6.65, 6.78-6.95, 7.12-7.55 (total 11H, m)

[1253] The compound of Example 744 1H-NMR (200 MHz, CDCl3) δ ppm: 1.32-2.26, 2.45-2.65, 2.65-3.30, 4.85-5.12 [total 11H, m, 2.53 (s)], 6.65-6.75, 6.75-7.06, 7.06-7.54, 7.54-7.96, 8.58-8.76 (total 11H, m)

[1254] The compound of Example 745 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.0-2.2, 2.7-4.8 (total 28H, m), 6.15-7.35 (11H, m), 10.3-10.95 (1H, m)

[1255] The compound of Example 747 1H-NMR (200 MHz, CDCl3) δ ppm: 0.75-1.00, 1.15-2.35, 2.35-4.27, 4.45-4.80 [total 32H, m, 3.38 (s)], 6.75-7.55 (7H, m), 12.6-13.4 (1H, br)

[1256] The compound of Example 748 1H-NMR (200 MHz, CDCl3) δ ppm: 0.66-1.10, 1.10-1.49, 1.49-2.34, 2.34-4.23, 4.35-4.80 (total 38H, m), 6.73-7.55 (7H, m), 12.6-13.5 (1H, br)

[1257] The compound of Example 749 1H-NMR (200 MHz, CDCl3) δ ppm: 0.75-0.96, 0.96-2.22, 2.22-4.30, 4.30-4.83 [total 27H, m, 4.58 (s), 2.49 (s)], 6.48-7.53 (11H, m), 12.75-13.45 (1H, br)

[1258] The compound of Example 751 1H-NMR (200 MHz, CDCl3) δ ppm: 0.78-1.05, 1.15-4.30, 4.42-4.75 [total 33H, m, 0.93, 0.99 and 2.33 (each s)], 6.68-7.89 (8H, m)

[1259] The compound of Example 752 1H-NMR (200 MHz, CDCl3) δ ppm: 0.52 (3H, d, J=6.6 Hz), 0.97 (3H, d, J=6.6 Hz), 1.10-2.20, 2.20-3.20, 3.35-4.15 [total 13H, m, 2.62 (s)], 6.35-6.55, 7.00-7.60, 7.60-8.05 (total 10H, m), 8.65-8.80 (1H, m)

[1260] The compound of Example 753 1H-NMR (200 MHz, CDCl3) δ ppm: 1.25-2.45, 2.45-4.30, 4.30-4.90 (total 23H, m), 6.45-8.55 (total 11H, m), 8.75-9.00 (1H, m)

[1261] The compound of Example 756 1H-NMR (200 MHz, DMSO-d6) δ ppm: 0.7-0.95, 0.95-2.25, 2.60-4.20, 4.20-4.55 [total 34H, m, 0.8 (d, J=6.6 Hz), 2.66 (s)], 6.75-7.95, 8.29, 8.57 [total 8H, m, 7.62, 7.83, 8.29, 8.57 each (s)]

[1262] The compound of Example 759 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.09-2.19 [12H, m, 1.25 (t, J=7.2 Hz)], 2.28-3.67, 4.24-4.57, 4.68-4.98 [total 10H, m, 2.41 (s)], 6.68-7.81 (11H, m), 10.26-10.64 (1H, m)

[1263] The compound of Example 764 1H-NMR (200 MHz, DMSO-d6) δ ppm: 0.64-2.12 [11H, m, 0.75, 0.89 (each d, each J=6.5 Hz)], 2.12-5.05 [21H, m, 2.33 (s)], 6.37-7.52 (7H, m), 10.92-11.43 (1H, m)

[1264] The compound of Example 765 1H-NMR (200 MHz, CDCl3+DMSO-d6) δ ppm: 1.2-2.3 (4H, m), 2.5-3.4, 4.7-5.1, 5.3-5.6 (total 4H, each m), 6.5-7.5 (9H, m), 7.60 (1H, dd, J=7.5 Hz, J=7.5 Hz,), 7.95 (1H, d, J=7.5 Hz), 11.43 (1H, s)

[1265] The compound of Example 766 1H-NMR (200 MHz, CDCl3) δ ppm: 0.50 (3H, d, J=6.6 Hz), 0.76-1.40,1.50-2.18, 2.18-2.70, 2.70-4.18 [total 24H, m, 3.36 (s)], 6.28-6.42, 6.82-7.54 (total 8H, m)

[1266] The compound of Example 767 1H-NMR (200 MHz, CDCl3) δ ppm: 0.50 (3H, d, J=6.6 Hz), 0.69-1.05, 1.05-1.41, 1.41-2.19, 2.19-2.70, 2.95-4.15 (total 31H, m), 6.27-6.38, 6.75-7.52 (8H, m)

[1267] The compound of Example 768 1H-NMR (200 MHz, CDCl3) δ ppm: 0.55-0.65, 0.72-0.99, 1.20-1.44, 1.55-2.10, 2.10-2.90, 2.90-3.25, 3.25-4.10 (total 36H, m), 6.30-6.45, 6.75-6.94, 7.00-7.50 (total 8H, m)

[1268] The compound of Example 769 1H-NMR (200 MHz, CDCl3) δ ppm: 1.05-4.70, 4.89-5.12 [total 26H, m, 2.34 (s), 4.33 (t, J=5.4 Hz), 4.40 (t, J=5.3 Hz)], 6.72-7.70 (7H, m)

[1269] The compound of Example 770 1H-NMR (200 MHz, CDCl3) δ ppm: 0.61 (3H, d, J=6.6 Hz), 0.97 (3H, d, J=6.6 Hz), 1.15, 1.30, 1.55-2.15, 2.25-2.70, 2.90-3.20, 3.32-3.52, 3.60-3.95 (total 19H, m), 4.40-4.60 (4H, m), 6.20-6.40, 6.51-6.52, 6.82-7.55 (total 13H, m)

[1270] The compound of Example 771 1H-NMR (200 MHz, DMSO-d6) δ ppm: 0.82-2.25 [11H, m, 0.97 (d, J=6.6 Hz)], 2.29-4.98 [21H, m, 2.43 (s)], 6.49-7.79 (11H, m), 10.85-11.30 (1H, m)

[1271] The compound of Example 773 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.00-2.30 [7H, m, 1.28 (t, J=7.2 Hz)], 2.31-5.08 [21H, m, 2.43 (s), 3.76 (s)], 6.48-7.81 (11H, m), 10.81-11.31 (1H, m)

[1272] The compound of Example 774 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.01-2.38 (4H, m), 2.39-5.02 [24H, m, 2.43 (s), 3.76 (s), 3.81 (s)], 6.49-7.78 (11H, m), 10.47-11.08 (1H, m)

[1273] The compound of Example 775 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.01-2.28 [10H, m, 1.19 (t, J=7.1 Hz)], 2.29-5.02 [22H, m, 2.44 (s), 3.77 (s), 3.81 (s)], 6.49-7.81 (11H, m), 9.92-10.32 (1H, m)

[1274] The compound of Example 777 1H-NMR (200 MHz, CDCl3) δ ppm: 1.21-3.18, 3.58-3.85, 4.15-4.40, 4.82-5.15 [total 25H, m, 2.63 (t, J=5.73 Hz), 4.27 (t, J=5.8 Hz)], 6.41-7.01, 7.18-7.49, 7.75-7.92 [total 7H, m, 7.85 (d, J=8.5 Hz)]

[1275] The compound of Example 778 1H-NMR (200 MHz, CDCl3) δ ppm: 0.96 (6H, d, J=10.7 Hz), 1.21-4.11, 4.31-4.59, 5.01-5.22 [total 21H, m, 2.41 (s), 3.70 (s), 3.92 (d, J=6.6 Hz)], 6.49-7.67, 7.80-8.05 [total 8H, m, 7.92 (d, J=8.4 Hz)]

[1276] The compound of Example 779 1H-NMR (200 MHz, CDCl3) δ ppm: 1.35-1.86, 1.86-2.29, 2.40-2.63, 2.63-3.16, 3.32-3.52, 4.85-5.08 [total 11H, m, 2.52 (s), 2.57 (s)], 6.56-6.68, 6.82-7.56 (6H, m), 8.86, 8.97 (total 2H, each s), 9.17, 9.23 (total 1H, each s)

[1277] The compound of Example 780 1H-NMR (200 MHz, CDCl3) δ ppm: 1.38-1.66, 1.85-2.22, 2.62-3.16, 4.90-5.15 (8H, m), 3.71 (3H, s), 6.58-6.70 (1H, m), 6.70-6.82 (1H, m), 6.82-7.00 (2H, m), 7.12-7.31 (2H, m), 7.50-7.80 (3H, m), 7.60-7.70 (1H, m)

[1278] The compound of Example 781 1H-NMR (200 MHz, CDCl3) δ ppm: 1.35-2.20, 2.65-3.15, 4.92-5.13 (total 8H, m), 3.67 (3H, s), 6.55-6.84 (2H, m), 6.84-7.00 (2H, m), 7.00-7.19 (1H, m), 7.19-7.34 (2H, m), 7.73-7.85 (1H, m), 8.48-8.60 (1H, m), 8.60-8.72 (1H, m)

[1279] The compound of Example 783 1H-NMR (200 MHz, CDCl3) δ ppm: 1.19-4.68, 5.00-5.19 [total 27H, m, 2.36 (s), 3.75 (s)], 6.48-7.59 (7H, m)

[1280] The compound of Example 784 1H-NMR (200 MHz, CDCl3) δ ppm: 1.05-2.21, 2.55-3.19, 3.41-3.55, 3.65-3.80, 3.95-4.23, 4.89-5.12 [total 31H, m, 1.45 (s), 3.73 (s)], 6.51-6.74, 6.82-6.95, 7.19-7.35, 7.80-7.90 [total 7H, m, 7.84 (d, J=8.4 Hz)]

[1281] The compound of Example 785 1H-NMR (200 MHz, CDCl3) δ ppm: 1.0-4.0, 4.0-5.2 (total 29H, m), 6.1-8.2 (total 11H, m)

[1282] The compound of Example 786 1H-NMR (200 MHz, CDCl3) δ ppm: 1.0-1.4, 1.4-4.0, 4.0-5.2 (total 33H, m), 6.15-6.35, 6.6-8.25 (total 7H, m), 12.4-13.4 (1H, m)

[1283] The compound of Example 787 1H-NMR (200 MHz, CDCl3) δ ppm: 1.2-1.6, 1.6-2.2, 2.6-3.75, 3.9-4.6 (total 28H, m), 6.5-7.6, 7.8-8.2 (total 12H, m), 10.8-11.2 (1H, m)

[1284] The compound of Example 788 1H-NMR (200 MHz, CDCl3) δ ppm: 1.25-4.0, 4.35-4.55, 5.0-5.20 [total 30H, m, 2.33 (s), 2.82 (s), 3.63 (s)], 6.55-7.55 [total 6H, m, 6.6 (d, J=6.6 Hz), 6.96 (d, J=6.6 Hz), 7.20 (d, J=6.6 Hz), 7.49 (s)]

[1285] The compound of Example 790 1H-NMR (200 MHz, CDCl3) δ ppm: 1.35-1.69, 1.78-2.26, 2.53-3.14, 3.30-3.81, 4.29-4.51, 4.90-5.18 [total 15H, m, 2.98 (t, J=5.3 Hz), 4.39 (t, J=5.3 Hz), 3.72 (s)], 6.45-7.35, 7.65-7.92, 8.40-8.65 (total 11H, m)

[1286] The compound of Example 794 1H-NMR (200 MHz, CDCl3) δ ppm: 1.11-3.95, 4.41-4.63, 4.95-5.15 [total 28H, m, 1.49 (s), 1.58 (s), 2.38 (s)], 6.75-7.92 (7H, m)

[1287] The compound of Example 795 1H-NMR (200 MHz, CDCl3) δ ppm: 1.11-4.05, 4.45-4.70, 4.81-5.13 [total 27H, m, 2.40 (s), 1.25 (d, J=6.2 Hz), 1.31 (d, J=6.3 Hz)], 6.60-7.82 (8H, m)

[1288] The compound of Example 796 1H-NMR (200 MHz, CDCl3) δ ppm: 1.35-2.18, 2.18-4.20, 4.25-470, 4.90-5.15 [total 24H, m, 3.85 (s)], 6.55-7.15, 7.15-7.60, 7.70-8.10 (total 21H, m)

[1289] The compound of Example 801 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.03-2.04 (10H, m), 2.31-3.88, 4.29-4.54, 4.84-5.07 [total 19H, m, 2.43 (s), 3.77 (s)], 6.50-7.78 (11H, m), 8.44-8.69 (1H, m), 9.91-10.27 (1H, m)

[1290] The compound of Example 802 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.05-2.36 [total 10H, m, 1.18 (t, J=7.0 Hz)], 2.48-4.54, 4.79-5.21 [total 19H, m, 3.60 (s)], 6.67-7.62 (11H, m), 10.04-10.39 (1H, m)

[1291] The compound of Example 803 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.05-2.10 (10H, m), 2.39-3.94, 4.18-4.49, 4.88-5.12 [total 16H, m, 3.58 (s)], 6.69-7.70 (11H, m), 8.34-8.71 (1H, m), 10.00-10.34 (1H, m)

[1292] The compound of Example 804 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.00-2.28 [10H, m, 1.23 (t, J=7.2 Hz)], 2.42-4.13, 4.26-4.52, 4.69-4.91 (total 19H, m), 6.76-7.85 (11H, m), 10.09-10.48, 11.10-11.26 (total 1H, m)

[1293] The compound of Example 805 1H-NMR (200 MHz, DMSO-d6) δ ppm: 0.99-2.06 [10H, m, 1.20 (t, J=7.0 Hz)], 2.38-4.08, 4.25-4.52, 4.72-4.92 (total 16H, m), 6.78-7.84 (11H, m), 8.43-8.68 (1H, m), 10.09-10.45 (1H, m)

[1294] The compound of Example 806 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.03-2.11 (4H, m), 2.34 (3H, s), 2.44-4.79, 4.88-5.10 (total 16H, m), 6.12-8.03 (11H, m), 11.08-11.55 (1H, m)

[1295] The compound of Example 807 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.03-2.13 (10H, m), 2.22-3.83, 4.17-4.48, 4.88-5.10 (total 16H, m, 2.35 (s)], 6.58-7.90 (11H, m), 8.39-8.81 (1H, m), 10.20-10.65 (1H, m)

[1296] The compound of Example 808 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.10-2.28 (4H, m), 2.52-4.68, 4.87-5.10 [total 22H, m, 3.51 (s), 3.65 (s)], 6.11-6.29, 6.42-7.65 (total 10H, m), 11.07-11.48 (1H, brs)

[1297] The compound of Example 809 1H-NMR (200 MHz, DMSO-d6) δ ppm: 0.95-2.26 (10H, m), 2.38-4.08, 4.20-4.52, 4.78-5.08 [total 19H, m, 3.58 (s), 3.75 (s)], 6.62-7.62 (10H, m), 8.36-8.68 (1H, m), 9.82-10.20 (1H, m)

[1298] The compound of Example 810 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.07-2.29 (4H, m), 2.30-4.78, 4.87-5.10 [total 22H, m, 3.51 (s), 3.65 (s)], 6.11-6.29, 6.42-7.63 (total 10H, m), 11.13-11.58 (1H, brs)

[1299] The compound of Example 811 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.03-2.30 (10H, m), 2.40-4.00, 4.18-4.76, 4.83-5.08 [total 19H, m, 3.58 (s), 3.75 (s)], 6.63-7.64 (10H, m), 8.34-8.71 (1H, m), 9.92-10.39 (1H, m)

[1300] The compound of Example 812 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.05-2.09 (4H, m), 2.30 (3H, s), 2.58-4.71, 4.88-5.08 [total 19H, m, 3.57 (s)], 6.12-7.68 (10H, m), 11.00-11.50 (1H, brs)

[1301] The compound of Example 813 1H-NMR (200 MHz, DMSO-d6) δ ppm: 0.96-2.19 [10H, m, 1.19 (t, J=7.0 Hz)], 2.31 (3H, s), 2.55-4.69, 4.82-5.08 [total 19H, m, 3.59 (s)], 6.14-7.63 (10H, m), 10.19-10.52, 11.00-11.30 (total 1H, m)

[1302] The compound of Example 814 1H-NMR (200 MHz, CDCl3) δ ppm: 1.15-2.30, 2.50-3.85, 4.48-4.67, 5.06-5.24 [total 15H, m, 2.56 (a), 3.72 (s)], 6.50-6.72 (1H, m), 6.72-7.95 (9H, m), 8.75 (1H, m)

[1303] The compound of Example 820 1H-NMR (200 MHz, CDCl3) δ ppm: 0.75-1.00, 1.00-2.20, 2.60-3.05, 3.05-3.43, 3.43-3.96, 4.45-4.62 [total 24H, m, 1.59 (s), 3.19 (s), 3.69(s)], 6.80-7.50 (7H, m)

[1304] The compound of Example 821 1H-NMR (200 MHz, CDCl3) δ ppm: 0.70-1.00, 1.10-2.20, 2.60-3.95, 4.45-4.65, 5.02-5.15 (total 21H, m), 6.80-7.55 (7H, m)

[1305] The compound of Example 822 1H-NMR (200 MHz, CDCl3) δ ppm: 0.60-1.05, 1.15-2.20, 2.60-3.05, 3.15-3.95, 4.45-4.60, 5.02-5.15 (total 30H, m), 6.72-7.60 (7H, m)

[1306] The compound of Example 823 1H-NMR (200 MHz, CDCl3) δ ppm: 0.63-1.00, 1.10-2.20, 2.60-3.95, 4.45-4.60, 5.00-5.20 (total 27H, m), 6.68-7.58 (7H, m)

[1307] The compound of Example 825 1H-NMR (200 MHz, CDCl3) δ ppm: 1.20-2.20, 2.35-2.60, 2.60-3.85, 4.25-4.65 (total 16H, m), 6.40-6.66 (1H, m), 6.70-7.55 (11H, m)

[1308] The compound of Example 826 1H-NMR (200 MHz, CDCl3) δ ppm: 1.20-2.25, 2.25-3.26, 3.26-3.90, 4.50-4.70 [total 2H, m, 2.61 (s)], 6.72-6.85 (1H, m), 6.85-6.97 (1H, m), 7.00-7.35 (3H, m), 7.35-7.45 (1H, d, J=8.2 Hz), 7.56-7.78 (2H, m), 7.85-8.12 (2H, m), 8.20-8.38 (1H, m), 8.70-8.80 (1H, m)

[1309] The compound of Example 827 1H-NMR (200 MHz, CDCl3) δ ppm: 1.2-2.4 (4H, m), 2.7-3.8, 4.4-4.7, 4.9-5.2 (total 5H, each m), 6.8-8.4(7H, m)

[1310] The compound of Example 828 1H-NMR (200 MHz, CDCl3) δ ppm: 1.13-2.30 (4H, m), 2.35-4.08, 4.40-4.64, 4.92-5.20 [total 13H, m, 2.52 (s), 3.72 (s), 5.08 (s)], 6.48-7.62 (16H, m)

[1311] The compound of Example 829 1H-NMR (200 MHz, CDCl3) δ ppm: 1.13-2.26, 2.32-3.69, 4.81-5.20 [total 13H, m, 2.49 (s), 5.07 (s)], 6.57-7.63 (16H, m)

[1312] The compound of Example 833 1H-NMR (200 MHz, CDCl3) δ ppm: 0.86, 0.93, 1.07, 1.15-2.15, 2.60-3.80, 4.35-4.60 [total 23H, m, 0.86 (d, J=6.6 Hz), 0.93 (d, J=6.6 Hz), 1.07 (t, J=7 Hz) 6.75-7.60 (total 7H, m), 8.25-8.80 (1H, m)

[1313] The compound of Example 834 1H-NMR (200 MHz, CDCl3) δ ppm: 1.20-2.15, 2.55-3.85, 4.35-4.55, 4.67 [total 15H, m, 4.67 (s)], 6.70-7.40, 7.44, 7.50-7.90 [total 12H, m, 7.44 (s)]

[1314] The compound of Example 835 1H-NMR (200 MHz, CDCl3) δ ppm: 1.35-2.24, 2.39-2.62, 2.63-3.18, 3.29-3.99, 4.06-4.63, 4.83-5.11 [total 15H, m, 2.49 (s), 3.81 (t, J=6.0 Hz)], 6.58-7.62 (11H, m)

[1315] The compound of Example 836 1H-NMR (200 MHz, CDCl3) δ ppm: 0.67-1.03, 1.05-2.54, 2.55-4.28, 4.41-4.63, 5.00-5.21 [total 24H, m, 0.78 (d, J=6.6 Hz), 0.92 (d, J=6.6 Hz), 2.28 (d, J=7.2 Hz), 2.43 (s), 3.71 (s)], 6.40-7.41 (7H, m)

[1316] The compound of Example 840 1H-NMR (200 MHz,DMSO-d6) δ ppm: 0.65-0.98, 1.04-2.12, 2.13-3.70, 4.26-4.51, 4.81-5.02 [total 21H, m, 0.75 (d, J=6.5 Hz), 0.89 (d, J=6.5 Hz), 2.27 (d, J=7.1 Hz), 2.33 (s)], 6.38-7.42 (7H, m), 12.14-12.42 (1H, m)

[1317] The compound of Example 844 1H-NMR (200 MHz, CDCl3) δ ppm: 1.13-4.01, 4.48-4.72 [total 23H, m, 2.33 (s)], 5.10 (2H, d, J=10.3 Hz), 6.43-7.64 (16H, m)

[1318] The compound of Example 845 1H-NMR (200 MHz, CDCl3) δ ppm: 1.09-4.20, 4.50-4.70, 4.96-5.16 [total 23H, m, 2.36 (s)], 6.41-7.48 (12H, m)

[1319] The compound of Example 849 1H-NMR (200 MHz, CDCl3) δ ppm: 1.2-2.2 (4.5H, m), 2.7-3.0 [total 5H, m, 2.83 (s)], 3.1-3.3, 3.3-3.5, 3.6-3.85, 4.35-4.5, 5.05-5.35 [total 12.5H, m, 3.40 (t, J=7.4 Hz), 3.67 (s), 3.77 (s)], 6.62 (1H, d, J=8.1 Hz), 6.82 (1H, d, J=8.1 Hz), 6.9-7.4 (4H, m)

[1320] The compound of Example 850 1H-NMR (200 MHz, CDCl3) δ ppm: 0.95 (6H, d, J=6.2 Hz), 1.25-2.15, 2.7-3.3, 3.67, 3.72, 4.35-4.65, 5.10-5.4 [total 19H, m, 3.67 (s), 3.72 (s)], 6.26, 6.64, 6.73-6.78, 6.96, 7.12-7.4 [total 6H, m, 6.26 (d, J=8.1 Hz)], 6.64 (d, J=8.1 Hz), 6.96 (dd, J=8.1 Hz, J=2.2 Hz)]

[1321] The compound of Example 851 1H-NMR (200 MHz, CDCl3) δ ppm: 1.2-2.2, 2.7-3.05, 3.15-3.3, 3.4-4.0, 4.4-4.55, 4.6-4.8, 5.05-5.26 [total 20H, m, 3.69 (s), 3.71 (s)], 6.60-7.45 [total 6H, m, 6.63 (d, J=8.1 Hz), 6.85 (d, J=8.1 Hz)]

[1322] The compound of Example 852 1H-NMR (200 MHz, CDCl3) δ ppm: 1.17-2.30 (4H, m), 2.57-3.03, 3.09-3.33, 3.43-3.92, 4.38-4.63, 5.08-5.28 [total 10H, m, 3.62 (s), 3.70 (s)], 6.53-7.43 (10H, m)

[1323] The compound of Example 853 1H-NMR (200 MHz, CDCl3) δ ppm: 1.18-2.30 (4H, m), 2.60-3.05, 3.10-3.37, 3.46-4.33, 4.38-4.62, 5.08-5.29 [total 10H, m, 3.67 (s), 3.71 (s), 3.81 (s)], 6.52-7.46 (10H, m)

[1324] The compound of Example 854 1H-NMR (200 MHz, CDCl3) δ ppm: 1.19-2.46 [7H, m, 2.37 (s)], 2.58-3.04, 3.05-4.26, 4.38-4.63, 5.06-5.28 [total 11H, m, 3.67 (s), 3.71 (s)], 6.54-7.48 (10H, m)

[1325] The compound of Example 855 1H-NMR (200 MHz, CDCl3) δ ppm: 1.20-2.28 (4H, m), 2.39 (3H, s), 2.57-3.10, 3.11-4.35, 4.40-4.63, 5.08-5.30 [total 8H, m, 3.75 (s)], 6.47-6.71, 6.81-7.78 (total 11H, m)

[1326] The compound of Example 856 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.12-2.19 (4H, m), 2.57-4.08, 4.20-4.66, 4.81-5.08 [total 11H, m, 3.52 (s), 3.65 (s)], 6.62-7.62 (10H, m), 12.36 (1H, s)

[1327] The compound of Example 857 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.10-2.19 (4H, m), 2.43-4.14, 4.20-4.71, 4.83-5.10 [total 11H, m, 3.59 (s), 3.75 (s)], 6.67-7.65 (10H, m), 12.20-12.57 (1H, brs)

[1328] The compound of Example 858 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.13-2.38 [7H, m, 2.31 (s)], 2.51-4.02, 4.19-4.75, 4.82-5.08 [total 8H, m, 3.59 (s)], 6.62-7.80 (10H, m), 12.20-12.58 (1H, brs)

[1329] The compound of Example 859 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.18-2.18 (4H, m), 2.34 (3H, s), 2.48-4.12, 4.20-4.80, 4.89-5.12 (total 5H, m), 6.61-7.88 (11H, m), 12.12-12.60 (1H, m)

[1330] The compound of Example 868 1H-NMR (200 MHz, CDCl3) δ ppm: 1.06-2.69, 2.98-4.26, 4.60-4.81 [total 33H, m, 2.32 (s), 2.39 (s)], 6.42-7.45 (7H, m)

[1331] The compound of Example 869 1H-NMR (200 MHz, CDCl3) δ ppm: 1.68-2.72, 3.01-4.25, 4.65-4.92 [total 25H, m, 2.32(s), 2.47(s), 3.82 (s)], 6.46-7.12 (11H, m)

[1332] The compound of Example 871 1H-NMR (200 MHz, CDCl3) δ ppm: 2.16-2.98, 3.42-3.91, 4.02-4.25, 4.60-4.88, 5.02-5.40 [total 19H, m, 2.35 (s), 4.79 (s)], 6.61-7.05, 7.13-7.94 (total 12H, m)

[1333] The compound of Example 870 1H-NMR (200 MHz, CDCl3) δ ppm: 1.93-2.98, 3.29-4.59, 4.69-5.31 [total 23H, m, 2.35 (s), 3.60 (t, J=5.50 Hz), 4.35 (t, J=5.3 Hz)], 6.69-7.70 (7H, m)

[1334] The compound of Example 841 1H-NMR (200 MHz, CDCl3) δ ppm: 0.85-2.22, 2.55-3.31, 3.41-3.80, 4.05-4.31, 4.41-4.62 [total 25H, m, 3.69 (s)], 6.71-7.70 (7H, m)

[1335] The compound of Example 842 1H-NMR (200 MHz, CDCl3) δ ppm: 0.82-1.03,1.15-2.20, 2.45-4.62 [total 22H, m, 0.93 (s)], 6.48-8.21 (8H, m)

[1336] The compound of Example 843 1H-NMR (200 MHz, CDCl3) δ ppm: 1.10-2.41, 2.56-4.65, 4.90-5.16 (total 15H, m), 6.52-7.61 (7H, m), 9.39-10.05 (1H, m)

[1337] The compound of Example 860 1H-NMR (200 MHz, CDCl3) δ ppm: 1.15-2.25, 2.50-3.03, 3.10-3.30, 3.48-3.91, 4.25-4.55, 5.05-5.28 [total 19H, m, 3.71 (s), 3.74 (s), 4.40 (t, J=5.9 Hz)], 6.42-7.42, 7.71-7.99 [total 7H, m, 6.58 (d, J=8.3 Hz), 7.86 (d, J=8.3 Hz)]

[1338] The compound of Example 861 1H-NMR (200 MHz, CDCl3) δ ppm: 0.75-2.21, 2.51-3.31, 3.45-4.10, 4.30-4.60, 5.03-5.31 [total 24H, m, 0.95 (d, J=6.7 Hz), 3.92 (d, J=7.2 Hz), 3.72 (s), 3.74 (s)], 6.42-7.41, 7.65-8.00 [total 7H, m, 6.58 (d, J=8.3 Hz), 7.88 (d, J=8.3 Hz)]

[1339] The compound of Example 862 1H-NMR (200 MHz, CDCl3) δ ppm: 1.11-2.31, 2.51-3.32, 3.42-4.09, 4.30-4.58, 5.05-5.21 [total 19H, m, 3.79 (s), 4.44 (t, J=7.8 Hz)], 6.49-7.42 [6H, m, (d, J=8.3 Hz)]

[1340] The compound of Example 863 1H-NMR (200 MHz, DMSO-d6) δ ppm: 0.88 (6H, d, J=6.7 Hz), 1.10-2.07, 2.52-4.45, 4.85-5.02 [total 15H, m, 3.63 (s), 3.98 (d, J=7.2 Hz)], 6.50-6.88, 6.98-7.29, 7.38-7.79, 8.28-8.49 [total 7H, m, 6.70 (d, J=8.3 Hz), 7.52 (d, J=8.3 Hz)]

[1341] The compound of Example 864 1H-NMR (200 MHz, DMSO-d6) δ ppm: 1.01-2.10, 2.39-4.51, 4.86-5.05 [total 13H, m, 3.67 (s)], 6.0-7.75 (6H, m), 9.99 (1H, s)

[1342] The compound of Example 865 1H-NMR (200 MHz, CDCl3) δ ppm: 1.11-2.21, 2.60-3.29, 3.41-3.90, 4.41-4.65, 4.82-5.20 [total 19H, m, 1.26 (d, J=6.4 Hz), 3.69 (s)], 6.53-7.80 [total 8H, m, 6.71 (s), 7.46 (s)]

[1343] The compound of Example 867 1H-NMR (200 MHz, CDCl3) δ ppm: 1.11-2.29, 2.68-3.92, 4.38-4.70, 5.01-5.19 [total 20H, m, 1.50 (s), 1.58 (s), 2.16 (s), 3.70 (s)], 6.78-7.90 [total 7H, m, 7.59 (d, J=2.1 Hz)]

[1344] The compound of Example 873 1H-NMR (200 MHz, CDCl3) δ ppm: 0.80-2.61, 2.88-3.72, 3.85-4.40, 4.62-5.01 [total 27H, m, 1.31 (t, J=7.0 Hz), 2.35 (s), 4.22 (q, J=7.1 Hz)], 6.41-7.49 (7H, m)

[1345] The compound of Example 874 1H-NMR (200 MHz, CDCl3) δ ppm: 1.18-1.48,1.68-2.62, 2.95-4.41, 4.71-5.05 [total 19H, m, 1.31 (t, J=7.1 Hz), 2.50 (s), 3.80 (s), 4.22 (q, J=6.8 Hz)], 6.45-7.65 (total 11H, m)

[1346] The compound of Example 875 1H-NMR (200 MHz, CDCl3) δ ppm: 1.10-2.62, 2.90-3.70, 3.85-4.21, 4.65-4.95 [total 22H, m, 2.35 (s)], 6.35-7.45 (7H, m)

[1347] The compound of Example 876 1H-NMR (200 MHz, CDCl3) δ ppm: 1.69-2.62, 2.81-4.28, 4.65-4.98 [total 14H, m, 2.43 (s), 3.80 (s)], 6.41-7.62 [11H, m, 7.38 (d, J=9.2 Hz)]

[1348] The compound of Example 877 1H-NMR (200 MHz, CDCl3) δ ppm: 1.53 (9H, s), 1.71-2.24, 2.50-2.91, 3.40-4.45, 4.61-5.10 [total 12H, m, 3.59 (t, J=6.3 Hz), 4.28 (t, J=6.0Hz)], 6.65-7.80, 8.55-8.68 (total 8H, m)

[1349] The compound of Example 878 1H-NMR (200 MHz, CDCl3) δ ppm: 1.53 (9H, s), 2.09-2.31, 2.52-2.82, 3.55-4.51, 4.62-5.09 [total 12H, m, 2.17 (t, J=5.1 Hz), 4.37 (t, J=5.5 Hz)], 6.89-7.71 (7H, m)

[1350] The compound of Example 879 1H-NMR (200 MHz, CDCl3) δ ppm: 2.05-2.90, 3.46-5.10 [total 12H, m, 3.60 (t, J=5.8 Hz), 4.38 (t, J=5.3 Hz)], 6.81-7.71 (7H, m), 10.1-10.6 (1H, m)

[1351] The compound of Example 880 1H-NMR (200 MHz, DMSO-d6) δ ppm: 2.51-2.88, 3.10-5.15 [total 6H, m, 4.94 (s)], 6.70-7.35, 7.45-7.85, 7.92-8.28, 8.55-8.65 (total 13H, m)

[1352] The compound of Example 881 1H-NMR (200 MHz, CDCl3) δ ppm: 1.12-1.41, 2.51-2.86, 3.69-4.01, 4.10-4.48, 4.62-4.98 [total 13H, m, 1.29 (t, J=4.0 Hz), 4.69 (s)], 6.65-7.10, 7.19-7.92 [total 12H, m, 7.73 (d, J=8.8 Hz), 7.84 (d, J=7.0 Hz)]

[1353] The compound of Example 882 1H-NMR (200 MHz, DMSO-d6) δ ppm: 2.30-2.76, 3.56-3.96, 4.27-4.80 (total 4H, m), 4.94 (2H, s), 6.71-7.90 (8H, m)

[1354] The compound of Example 883 1H-NMR (200 MHz, CDCl3) δ ppm: 1.60-2.09, 2.28-4.32, 4.60-5.10 (total 10H, m), 6.41-8.25, 8.41-8.90 [total 13H, m, 8.12 (d, J=7.4 Hz)]

[1355] The compound of Example 884 1H-NMR (200 MHz, CDCl3) δ ppm: 1.05-1.49,2.25-4.99 [total 15H, m, 1.31 (t, J=7.1 Hz)], 6.60-7.90, 8.00-8.28 [total 12H, m, 8.12 (d, J=7.7 Hz)]

[1356] The compound of Example 885 1H-NMR (200 MHz, DMSO-d6) δ ppm: 0.85-4.70, 4.88-6.20 (total 11H m), 6.51-8.62 [total 12H, m, 7.94 (d, J=7.2 Hz)]

[1357] The compound of Example 866 1H-NMR (200 MHz, CDCl3) δ ppm: 0.85-2.18, 2.45-3.90, 4.29-4.60, 4.78-5.18 [total 16H, m, 1.28 (d, J=7.2 Hz)], 6.40-7.81 (8H, m), 7.90-9.60 (1H, m)

[1358] The compound of Example 789 1H-NMR (200 MHz, CDCl3) δ ppm: 0.4-1.4, 1.4-2.4, 2.4-2.85, 2.85-3.3, 3.3-5.0, 5.0-5.8 (total 29H, m), 6.29, 6.5-7.5 [total 6H, m, 6.29 (d, J=8.4 Hz)]

[1359] The compound of Example 792 1H-NMR (200 MHz, CDCl3) δ ppm: 0.75-0.98, 1.21-2.20, 2.42-4.19, 4.85-5.19 [total 25H, m, 2.60 (s), 3.73 (s)], 6.45-6.75, 6.80-7.00 (total 5H, m), 7.23 (1H, d, J=2.4 Hz), 7.81 (1H, d, J=6.6 Hz)

[1360] The compound of Example 797 1H-NMR (200 MHz, CDCl3) δ ppm: 1.03-1.40, 1.50-2.23, 2.23-2.58, 2.53-4.05, 4.05-4.30, 4.52-4.73 [total 24H, m, 1.60 (s), 2.13 (s)], 6.55-7.05, 7.05-7.50 (total 20H, m)

[1361] The compound of Example 798 1H-NMR (200 MHz, CDCl3) δ ppm: 1.30-2.20, 2.62-3.18, 4.85-5.05 (total 8H, m), 3.68 (3H, brs), 6.67-6.90, 7.00-7.50 (total 7H, m), 7.75-7.85 (1H, m), 8.50-8.65 (1H, m), 8.65-8.85 (1H, m)

[1362] The compound of Example 799 1H-NMR (200 MHz, CDCl3) δ ppm: 1.30-1.80, 1.80-2.20, 2.62-2.93, 2.93-3.20, 4.82-5.03 (total 8H, m), 3.71 (3H, s), 6.69-6.85 (2H, m), 7.10-7.48 (5H, m), 7.60-7.80 (2H, m), 8.60-8.70 (1H, m)

[1363] Pharmacological Test

[1364] Experiment 1: V1 Receptor Binding Assay

[1365] Using rat liver plasma membrane preparations prepared according to Ichihara's method [cf: Akira Ichihara, J. Bio. Chem., 258, 9283 (1983)], the plasma membrane (50000 dpm, 2×10−10 M) of [3H]-Arg-vasopressin and a test compound (60 μg, 10−8 to 10−4 M) are incubated at 37° C for 10 minutes in 100 mM Tris-HCl buffer (pH 8.0) (250 μl) containing 5 mM MgCl2, 1 mM EDTA and 0.1% BSA. After incubation, the mixture is filtered three times using the glass filter (GF/F) so as to separate the membrane preparation binding with vasopressin and then washed with the buffer (5 ml). This glass filter is taken cut and mixed with liquid scintillation cocktail. The amount of [3H]-vasopressin binding with the membrane is measured by liquid scintillation counter and the rate of the inhibitory effect of the test compound is estimated according to the following equation.

Rate of the inhibitory effect (%)=100−[(C1−B1)/(C0−B1)]×100

[1366] C1: The amount of [3H]-vasopressin binding with the membrane in the presence of the test compound (known amount)

[1367] C0: The amount of [3H]-vasopressin binding with the membrane in the absence of the test compound

[1368] B1: The amount of [3H]-vasopressin binding with the membrane in the presence of the excess amount of vasopressin (10−6 M)

[1369] The results are expressed as IC50 value, which is the concentration of the test compound required to achieve the inhibitory effect in the rate of 50%.

[1370] The results are shown in the following Table.

[1371] Experiment 2: V2 Receptor Binding Assay

[1372] Using rat kidney plasma membrane preparations prepared according to OHechter's method [cf: J. Bio. Chem., 253, 3211 (1978)], the plasma membrane (100000 dpm, 4×10−10 M) of [3H]-Arg-vasopressin and a test compound (0.6 mg, 10−10 to 10−5 M) are incubated at 4° C. for 3 hours in 100 mM Tris-HCl buffer (pH 8.0) (250 μl) containing 5 mM MgCl2, 1 mM EDTA and 0.1% BSA. After incubation, the mixture is filtered using the glass filter (GF/F) so as to separate the membrane preparation binding with vasopressin and then washed twice with the buffer (each 5 ml). This glass filter is taken out and mixed with liquid scintillation cocktail. The amount of [3H]-vasopressin binding with the membrane is measured by liquid scintillation counter and the rate of the inhibitory effect of the test compound is estimated according to the following equation.

Rate of the inhibitory effect (%)=100−[(C1−B1)/(C0−B1)]×100

[1373] C1: The amount of [3H]-vasopressin binding with the membrane in the presence of the test compound (known amount)

[1374] C0: The amount of [3H]-vasopressin binding with the membrane in the absence of the test compound

[1375] B1: The amount of [3H]-vasopressin binding with the membrane in the presence of the excess amount of vasopressin (10−6 M)

[1376] The results are expressed as IC50 value, which is the concentration of the test compound required to achieve the inhibitory effect in the rate of 50%.

[1377] The results are shown in the following Table.

16IC50 (μM) in V1IC50 (μM) in V2 receptorTest compoundreceptor binding assaybinding assayCompound of Ex. 290.0210.15

[1378] Experiment 3: Anti-vasopressor Activity in vivo

[1379] The spinal cord of mal SD rat (weighing 300-400 g) is broken to give a pith rat. The blood pressure of the pith rat is measured through the cannula inserted into the femoral artery thereof by using a pressure transducer. The test compound and Arg-vasopressin are administered to the pith rat through the cannula inserted into the femoral vein. Anti-vasopressor activity of the test compound in vivo is determined according to the following equation.

Anti-vasopressor activity (%)=P/P0×100

[1380] P0: The increase of diastolic pressure when Arg-vasopressin (30 mU/kg) is administered intravenously.

[1381] P: The increase of diastolic pressure when Arg-vasopressin (30 mU/kg) is administered intravenously 3 minutes after the intravenous administration of the test compound.

[1382] The results are expressed as ED50 value, which is the dose of the test compound required to reduce the increase of diastolic pressure caused by the intravenous administration of Arg-vasopressin (30 mU/kg) to 50% of its control value: P0.

[1383] The results are shown in the following Table.

17Test compoundED50 (mg/kg)Compound of Ex. 291.0Compound of Ex. 702.8

[1384] Experiment 4: Anti-antidiuretic Activity (Effect on Endogenous ADH)

[1385] A test compound or a solvent (dimethylformamide) is administered into a caudal vein of untreated, unrestrained SD rats (male, weight: 300-350 g) and the amount of urine, which is spontaneously excreted for a period of two hours thereafter, is collected and measured by using a metabolic gauge. During this measurement, the rats are allowed to take water and feed freely.

[1386] In the group treated by administration of the compound of Example 493 at a dose of 10 mg/kg, the amount of urine, which is excreted for two hours from the administration of the test compound, is four times larger than that in the control group.

[1387] Experiment 5: Antidiuretic Activity

[1388] A test compound is dissolved in polyethylene glycol 400 or water, or suspended in 5% gum arabic solution to give a test compound solution.

[1389] The test compound solution is orally and forcibly administered to untreated, unrestrained Brattleburo rats, which hereditarily lack vasopressin. In the control group, a solvent is administered instead of a test compound solution. After the administration, the rats are put into a metabolic gauge, and the spontaneously excreted urine is collected for two hours, and the amount thereof is measured. During this measurement, the rats are allowed to take water and feed freely.

[1390] In the group treated by oral administration of Example 562 at a dose of 1 mg/kg, the amount of the urine, which is excreted for two hours after the administration of the test compound, is one fifth of that in the control group.

Number	Date	Country	Kind
132355/1994	Jun 1994	JP
70727/1995	Mar 1995	JP

	Number	Date	Country
Parent	09431635	Nov 1999	US
Child	09874452	Jun 2001	US
Parent	08737432	Nov 1996	US
Child	09431635	Nov 1999	US

Benzoheterocyclic derivatives

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