Pyridine compounds which are useful as leukotriene B4 antagonist

BACKGROUND OF THE INVENTION
1. Technical Field
The present invention relates to compounds effective as leukotriene B.sub.4 antagonists.
More particularly, this invention relates to leukotriene B.sub.4 antagonists, to processes for producing them and to pharmaceutical compositions containing at least one of those leukotriene B.sub.4 antagonists, which have excellent anti-leukotriene B.sub.4 activity and are useful as an anti-allergic agent or an anti-inflammatory agent.
2. Prior Art
In 1979 B. Sammuelsson reported the isolation and biological effects of leukotrienes (B. Sammuelsson et al. (1980): Advances in Prostaglandin and Thromboxane Research, Vol. 6, edited by B. Sammuelsson, R. Ramwell, and R. Paaletti, P. I. Raven Press, New York).
Since then, a tremendous amount of research in the synthetic organic chemistry and pharmacology of leukotriene A.sub.4, B.sub.4, C.sub.4, D.sub.4, etc. has been performed.
Leukotrienes induce an increase in capillary permeability and cause smooth muscle contraction. Leukotriene B.sub.4, one of leukotrienes which is shown below, has different pharmacological properties from the others. It is chemotactic for macrophages and neutrophils at concentrations of .about.1 ng/ml (greater than any other known lipid chemotactic factor). It is detected in the synovia of patients with rheumatoid arthritis or gouty arthritis, and in the sputum of obstructive airways diseases which suggest that it is a primary mediator of inflammatory and allergic states. ##STR2##
In recent research some compounds having an antagonism on LTB.sub.4 have been reported. For example, ##STR3##
SUMMARY OF THE INVENTION
In accordance with the present invention, leukotriene B.sub.4 antagonists of the following general formula [I] and their non-toxic pharmaceutically acceptable salts are provided, which have potent anti-leukotriene B.sub.4 activity which include suppression of chemotaxis, degranulation and O.sub.2 -production of leukocytes, and modulation of lymphocytes activity, etc. This action may render these compounds very useful as the drugs for the treatment of inflammatory states or immunological disorders such as allergy, rheumatoid arthritis, and inflammatory bowel disease.
DISCLOSURE OF THE INVENTION
The novel leukotriene B.sub.4 antagonists provided by the present invention are those represented by the formula [I]: ##STR4## wherein A is a C.sub.1 -C.sub.5 alkylene chain;
B is a phenylene or 6 membered heteroaromatic group which is constituted by carbon atoms and one or two nitrogen atoms, and B may be, optionally substituted with one or two substituents selected from the group, consisting of a C.sub.1 -C.sub.5 alkyl group, a C.sub.1 -C.sub.5 alkoxy group, a hydroxyl group, a carboxyl group, a nitro group and a halogen atom;
R.sup.1 is a C.sub.1 -C.sub.5 alkyl group;
R.sup.2 is a hydroxyl group or a C.sub.1 -C.sub.5 alkoxy group;
R.sup.3 and R.sup.4 are each independently a hydrogen atom, a C.sub.1 -C.sub.5 alkyl group, a C.sub.2 -C.sub.5 alkenyl group or a C.sub.2 -C.sub.5 alkynyl group;
R.sup.5 is a hydrogen atom, a C.sub.1 -C.sub.5 alkyl group or a hydroxy C.sub.1 -C.sub.5 alkyl group;
R.sup.6 is a group of the formula:
--X--Y--Z--R.sup.6 '
wherein
X is a phenylene group or a monocyclic 5.about.6 membered hetero aromatic group, and X is optionally substituted with one or two substituents selected from the group consisting of a C.sub.1 -C.sub.5 alkyl group, a hydroxyl group, a carboxyl group, a nitro group and a halogen atom;
Y is a single bond or an oxygen atom;
Z is a single bond or a C.sub.1 -C.sub.5 alkylene chain;
provided that when Y is an oxygen atom,
X is a phenylene group and Z is a C.sub.1 -C.sub.5 alkylene chain;
R.sup.6 ' is a COOR.sup.7 group,
a CONR.sup.8 R.sup.9 group,
a CONHCHR.sup.20 (CH.sub.2).sub.n COOR.sup.7 group,
a CONHCHR.sup.20 (CH.sub.2).sub.n CONR.sup.8 R.sup.9 group,
a CONHCHR.sup.20 CONHCHR.sup.22 CO.sub.2 R.sup.7 group or
a sulfamoyl group,
wherein
R.sup.7 is a hydrogen atom, a benzyl group, a C.sub.1 -C.sub.5 alkyl group or an C.sub.1 -C.sub.5 alkyl group substituted with an aminoheteroaromatic group wherein the heteroaromatic group is a monocyclic 5.about.6 membered heteroaromatic group;
R.sup.8 and R.sup.9 are each independently a hydrogen atom, a C.sub.1 -C.sub.5 alkyl group, hydroxy C.sub.1 -C.sub.5 alkyl group, a hydroxyethylpyridyl group or a hydroxyethylthiazolyl group, or the group of the formula:
--NR.sup.8 R.sup.9
represents a pyrrolidino, a piperidino or a morpholino group;
R.sup.20 is a hydrogen atom, a hydroxyl group, a C.sub.1 -C.sub.5 alkyl group, a phenyl group, a hydroxyphenyl group, a benzyl group, a hydroxy benzyl group or a substituted C.sub.1 -C.sub.5 alkyl group wherein the substituent is selected from the group consisting of a hydroxyl group, a C.sub.1 -C.sub.5 alkoxy group, a mercapto group, a methylthio group, an amino group, an indolyl group, an imidazolyl group, a carboxyl group, a C.sub.1 -C.sub.5 alkoxycarbonyl group, a carbamoyl group and a quanidino group;
n is 0, 1, 2, 3, 4 or 5; and
R.sup.22 is a hydrogen atom, a C.sub.1 -C.sub.5 alkyl group or a C.sub.1 -C.sub.5 hydroxyalkyl group;
or R.sup.6 is a CHR.sup.20 (CH.sub.2).sub.n COOR.sup.7 group,
a CH.sub.2 CHR.sup.20 COOR.sup.7 group,
a CHR.sup.20 (CH.sub.2).sub.n CONR.sup.8 R.sup.9 group,
a CH.sub.2 CHR.sup.20 CONR.sup.8 R.sup.9 group,
a CHR.sup.20 (CH.sub.2).sub.n OH group,
a CR.sup.20 R.sup.22 (CH.sub.2).sub.n OH group,
a CH.sub.2 CHR.sup.20 OH group, or
a CHR.sup.20 CONHCHR.sup.22 CO.sub.2 R.sup.7 group,
wherein R.sup.7, R.sup.8, R.sup.9, R.sup.20, R.sup.22 and n are as defined above, or the group of the formula: ##STR5## represents an azetidino group, pyrrolidino group, a piperidino group or a homopiperidino group, which is optionally substituted with one to two substituents selected from the group consisting of a hydroxyl group, a C.sub.1 -C.sub.5 hydroxyalkyl group, carboxyl group, C.sub.1 -C.sub.5 alkoxycarbonyl group and benzyloxycarbonyl group; or pharmaceutically acceptable salts thereof.
In the definitions as used above, the term "C.sub.1 -C.sub.5 alkylene" means a straight or branched chain C.sub.1 -C.sub.5 alkylene (e.g. methylene, ethylene, trimethylene, tetramethylene, pentamethylene, 1-methyethylene, 2-ethyltrimethylene, etc.).
The term "C.sub.1 -C.sub.5 alkyl" means a straight or branched chain C.sub.1 -C.sub.5 alkyl (e.g. methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, iso-pentyl, sec-pentyl, neo-pentyl, etc.).
The term "C.sub.2 -C.sub.5 alkenyl" means a straight or branched chain C.sub.2 -C.sub.5 alkenyl (e.g. 1-methylethenyl, 1-ethylethenyl, 1-propenyl, 2-propenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 1,2-dimethyl-1-propenyl, 1-n-butenyl, 2-n-butenyl, 3-n-butenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl, 3-methyl-1-butenyl, 1-methyl-2-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, etc.).
The term "C.sub.2 -C.sub.5 alkynyl" means a straight or branched chain C.sub.2 -C.sub.5 alkynyl (e.g. ethynyl, 1-propynyl, 2-propynyl, 1-methyl-2-propynyl, 1-n-butynyl, 2-n-butynyl, 3-n-butynyl, 3-methyl-1-butynyl, 1-methyl-2-butynyl, 2-methyl-3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, etc.).
The term "C.sub.1 -C.sub.5 alkoxy" means alkoxy having C.sub.1 -C.sub.5 alkyl moiety (e.g. methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxy, sec-butoxy, tert-butoxy, n-pentoxy, iso-pentoxy, sec-pentoxy, neo-pentoxy, etc.).
The term "6 membered heteroaromatic group which is constituted by carbon atoms and one or two nitrogen atoms" includes pyridinediyl, pyrazinediyl, pyrimidinediyl, etc.
The term "monocyclic 5.about.6 membered heteroaromatic group" contains, for example, 1-3 hetero atoms which can be a nitrogen, oxygen or sulfur atom, or an oxydized nitrogen atom (N.fwdarw.O), and examples of the monocyclic 5-6 membered heteroaromatic group are a pyridinediyl group and any one of the group of the formula (i)-(viii): ##STR6##
The term "hydroxyphenyl group" may be a 2-hydroxyphenyl, a 3-hydroxyphenyl or a 4-hydroxyphenyl group.
The term "hydroxybenzyl group" may be a 2-hydroxybenzyl, a 3-hydroxybenzyl or a 4-hydroxybenzyl group.
The term "halogen" may be a chlorine, a bromine or a fluorine atom.
The term "indolyl group" may be a 2-indolyl or 3-indolyl group.
The term "imidazolyl group" may be a 4-imidazolyl group.
A basic object of the present invention is to provide novel compounds effective as leukotriene B.sub.4 antagonists [I] having excellent pharmacological activities.
Another object of the present invention is to provide processes for producing those compounds [I]. A further object of the present invention is to provide a pharmaceutical composition containing a compound of the formula [I]. These and other objects will be apparent to those skilled in the art to which the present invention pertains from the foregoing and subsequent descriptions.
The novel leukotriene B.sub.4 antagonists [I] of the invention can be prepared by the following methods: ##STR7## wherein A, B, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 ', X, Y, Z and R.sup.20 are as defined above, and
R.sup.11 is the same as R.sup.6 ', but it does not means free carboxylic group;
R.sup.12 is a group of the formula:
X-Y-Z-COOR.sup.7',
X-Y-Z-CONHCHR.sup.20 (CH.sub.2).sub.n COOR.sup.7',
X-Y-Z-CONHCHR.sup.20 CONHCHR.sup.22 CO.sub.2 R.sup.7',
CHR.sup.20 (CH.sub.2).sub.n COOR.sup.7',
CH.sub.2 CHR.sup.20 COOR.sup.7', or
CHR.sup.20 CONHCHR.sup.22 COOR.sup.7',
wherein
X, Y, Z, R.sup.20, R.sup.22 and n are as defined above, and R.sup.7' is the same as R.sup.7 but it does not mean a hydrogen atom,
R.sup.13 is a group of the formula:
X-Y-Z-COOH,
X-Y-Z-CONHCHR.sup.20 (CH.sub.2).sub.n COOH,
X-Y-Z-CONHCHR.sup.20 CONHCHR.sup.22 CO.sub.2 H,
CHR.sup.20 (CH.sub.2).sub.n COOH,
CH.sub.2 CHR.sup.20 COOH, or
CHR.sup.20 CONHCHR.sup.22 COOH,
wherein
X, Y, Z, R.sup.20, R.sup.22 and n are as defined above,
R.sup.14 is a group of the formula:
(CH.sub.2).sub.n COOR.sup.7', or
CONHCHR.sup.22 COOR.sup.7',
wherein
R.sup.7', R.sup.22 and n are as defined above,
R.sup.15 is a group of the formula:
COOR.sup.7',
CONHCHR.sup.20 (CH.sub.2).sub.n COOR.sup.7', or
CONHCHR.sup.20 CONHCHR.sup.22 CO.sub.2 R.sup.7',
wherein
R.sup.7', R.sup.20, R.sup.22 and n are as defined above,
R.sup.16 is a group of the formula:
COOH,
CONHCHR.sup.20 (CH.sub.2).sub.n COOH, or
CONHCHR.sup.20 CONHCHR.sup.22 CO.sub.2 H,
wherein
R.sup.20, R.sup.22 and n are as defined above,
R.sup.26 is a group of the formula:
(CH.sub.2).sub.n COOH, or
CONHCHR.sup.22 COOH, wherein R.sup.22 and n are as defined above.
Method A
The amide compound [IV] or [IX] can be prepared from an acid compound [II] or [VII] by reacting an amine compound [III] or [VIII] in the presence of a condensing agent (e.g. dicyclohexylcarbodiimide, ethyldimethylaminopropylcarbodiimide hydrochloride, etc.), hydroxybenzotriazole and a tertiary amine (e.g. triethylamine, 4-dimethylaminopyridine, etc.) in an inert solvent (e.g. dichloromethane, mixed solvent of dichloromethane and N,N-dimethylformamide, etc.) at a temperature in the range from 0.degree. C. to the boiling temperature of the solvent.
If a substituent of R.sup.20 of compound [VIII] is an impediment group (e.g. mercapto, carboxyl, amino group, etc.), the compound is previously protected by a protecting group (e.g. benzyl, benzyloxycarbonyl, t-butoxycarbonyl group, etc.), and after the reaction is carried out, the protecting group is eliminated. The protection and deprotection of R.sup.20 can be carried out by the conventional procedure. [Protective Group in Organic Chemistry, Edited by J. F. W. McOmic (1973) 95-143].
Method B
The amide compound [IV] or [IX] can be obtained from an acid chloride or an acid anhydride of an acid compound [II] or [VII] by reacting with an amine compound [III] or [VIII] in the presence of a tertiary amine (e.g. triethylamine, etc.), or by reacting with a salt of an amine compound [III] or [VIII] (e.g. sodium salt, potassium salt, etc.) in the absence of amine in an inert solvent (e.g. tetrahydrofuran, etc.) at a temperature in the range from 0.degree. C. to a boiling temperature of the solvent.
The transformation of an acid group to an acid chloride group can be carried out by treating the acid compound with phosphorous oxychloride or thionyl chloride in an inert solvent (e.g. chloroform, etc.) or in the absence of solvent at a temperature in the range of from -40.degree. C. to the boiling temperature of the reaction mixture.
The transformation of an acid group to an acid anhydride group can be carried out by treating the acid compound with chloroformate ester (e.g. ethyl chloroformate, etc.) in the presence of a tertiary amine (e.g. triethylamine, etc.) in an inert solvent (e.g. chloroform, etc.) at a temperature in the range of from -40.degree. C. to the boiling temperature of the solvent.
If a substituent of R.sup.20 of compound [VIII] is a impediment group (e.g. mercapto, carboxyl, amino group, etc.), the compound is previously protected by a protecting group (e.g. benzyl group, benzyloxycarbonyl group, t-butoxycarbonyl group, etc.), and after the reaction is carried out, the protecting group is eliminated.
The protection and deprotection of R.sup.20 can be carried out by the conventional procedure [Protective Group in Organic Chemistry, Edited by J. F. W. McOmic (1973) 95-143].
Method C
The acid compound [VI], [X] or [XIV] can be prepared by hydrolysis of the ester compound [V], [IX] or [XIII] by treating with an aqueous alkali (e.g. sodium hydroxide, lithium hydroxide) in an inert solvent (e.g. tetrahydrofuran, methanol, ethanol, etc.).
Method D
The N-oxide compound [XII] can be prepared from pyridine compound [XI] by treating with an oxidizing agent (e.g. m-chloroperbenzoic acid, etc.) in an inert solvent (e.g. methylene chloride, etc.).
The amine compounds [III] and [VIII] are known compounds or easily obtained as described in e.g. J. Goto, K. Sakane, Y. Nakai, T. Teraji, The journal of antibiotics, 37, 532 (1984), I. Csendes, B. W. Muller, W. Tosch, The journal of antibiotics, 36, 1020 (1983), M. Ohta, Yakugaku zassi, 72, 1536 (1983), JP-A-58-23697. And, the starting compounds [II], [II-1] and [II-2] can be obtained by the following method. ##STR8## (wherein A, B, R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are as defined above, R.sup.17 is a C.sub.1 -C.sub.5 alkyl group, R.sup.18 is a C.sub.1 -C.sub.5 alkyl group, R.sup.18 is a C.sub.1 -C.sub.5 alkyl group, Hal is a chlorine or bromine atom)
Alkylation of the compound [XV] into the compound [XVII] can be accomplished by treating the former with the compound [XVI] in an inert solvent (e.g. N,N-dimethylformamide, etc.) in the presence of a base (e.g. anhydrous potassium carbonate, etc.). Optionally, the compound [XVII] can be alkylated to produce the compound [XVIII] by the same procedure as used in the synthesis of the compound [XVII] from the compound [XV]. And, the compound (II-1) and (II-2), respectively, can be prepared from the compound [XVII] and [XVIII] by hydrolysis (Method C).
The compound [XV] is a known compound or easily obtained as described in e.g. J. Hurst, J. Wibberley, Journal of Chemical Society, 1962, 119.
The compound [XVI] is obtained by;
(1) In the case where both Hal and B of compound [XVI] are jointed to the same carbon atom:
the compound [XVI] is a known compound or easily obtained as described in e.g. J. Hurst, J. Wibberley, Journal of Chemical Society, 1962, 119, etc,
(2) In the case that there are two carbon atoms between Hal and B in compound [XVI]: ##STR9## (wherein A, B and Hal are as defined above, R.sup.19 is a C.sub.1 -C.sub.5 alkyl group (but, there is at least one hydrogen atom at the .alpha. carbon bonded to B), R.sup.21, R.sup.23 are each independently a hydrogen atom or a C.sub.1 -C.sub.5 alkyl group, R.sup.24 is a C.sub.1 -C.sub.5 alkyl group, and R.sup.25 is a C.sub.1 -C.sub.5 alkyl group or phenyl group)
the compound [XVI] is prepared in the following way:
first step: the carboxylic acid group of a compound [XX] is protected to yield a 4,4-dimethyl-2-oxazoline compound,
second step: the 4,4-dimethyl-2-oxazoline compound is treated with a base to deprotonate a hydrogen atom attached to a carbon atom adjacent to B group (e.g. sodium amide, n-butyl lithium, etc.),
third step: the deprotected compound is reacted with the compound of the formula [XXI] (aldehyde or ketone) to yield a hydroxy compound,
fourth step: the hydroxyl compound is alkylated by reacting with a compound of the formula R.sup.24 -Hal, fifth step: the alkylated compound is treated with halogenated hydrogen (e.g. hydrogen chloride, hydrogen bromide, etc.) in the alcohol represented by R.sup.17 OH.
(3) In the case that there are 3 or more carbon atoms between Hal and B in the compound [XVI]:
the compound [XVI] is prepared in the same way, except modifying the alkylation reaction, as described in above (2), i.e., the compound [XX] is protected and deprotonated, and then alkylated by alkylhalide [XXII]. The alkylated product is treated with halogenated hydrogen (e.g. hydrogen chloride, hydrogen bromide, etc.) in the alcohol represented by R.sup.17 OH.
Specific examples of the leukotriene B.sub.4 antagonists are as follows:
TABLE 1__________________________________________________________________________ ##STR10##__________________________________________________________________________R.sup.3 H H H n-Pr H H H H HR.sup.4 Me n-Pr n-Pr H Et Et Et Et EtR.sup.5 H H H H CH.sub.3 Et n-Pr i-Pr HR.sup.6' CONH.sub.2 CONH.sub.2 CONH.sub.2 CONH.sub.2 CONH.sub.2 CONH.sub.2 CONH.sub.2 CONH.sub.2 CONHMe__________________________________________________________________________
TABLE 2__________________________________________________________________________ ##STR11##__________________________________________________________________________A CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 (CH.sub.2).sub.2 (CH.sub.2).sub.3 (CH.sub.2).sub.4 (CH.sub.2).sub.5R.sup.6' CONMe.sub.2 CONHiPr ##STR12## ##STR13## ##STR14## CONH.sub.2 CONH.sub.2 CONH.sub.2 CONH.sub.2__________________________________________________________________________
TABLE 3__________________________________________________________________________ ##STR15##__________________________________________________________________________A CHMe CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 ##STR16## ##STR17## ##STR18## ##STR19## ##STR20## ##STR21## ##STR22## ##STR23## ##STR24##Z CH.sub.2 single bond CH.sub.2 (CH.sub.2).sub.2 (CH.sub.2).sub.3 (CH.sub.2).sub.4 (CH.sub.2) .sub.5 CH.sub.2 single__________________________________________________________________________ bond
TABLE 4__________________________________________________________________________ ##STR25##__________________________________________________________________________ ##STR26## ##STR27## ##STR28## ##STR29## ##STR30## ##STR31## ##STR32## ##STR33## ##STR34##Z CH.sub.2 (CH.sub.2).sub.2 (CH.sub.2).sub.3 (CH.sub.2).sub.4 single bond CH.sub.2 (CH.sub.2).sub.2 (CH.sub.2).sub.3 (CH.sub.2).sub.4__________________________________________________________________________
TABLE 5__________________________________________________________________________ ##STR35##__________________________________________________________________________ ##STR36## ##STR37## ##STR38## ##STR39## ##STR40## ##STR41## ##STR42## ##STR43## ##STR44##X ##STR45## ##STR46## ##STR47## ##STR48## ##STR49## ##STR50## ##STR51## ##STR52## ##STR53##__________________________________________________________________________
TABLE 6__________________________________________________________________________ ##STR54##__________________________________________________________________________ ##STR55## ##STR56## ##STR57## ##STR58## ##STR59## ##STR60## ##STR61## ##STR62## ##STR63##X ##STR64## ##STR65## ##STR66## ##STR67## ##STR68## ##STR69## ##STR70## ##STR71## ##STR72##Z single bond CH.sub.2 (CH.sub.2).sub.2 (CH.sub.2).sub.3 (CH.sub.2).sub.4 single bond CH.sub.2 (CH.sub.2).sub.2 single__________________________________________________________________________ bond
TABLE 7__________________________________________________________________________ ##STR73##__________________________________________________________________________ ##STR74## ##STR75## ##STR76## ##STR77## ##STR78## ##STR79## ##STR80## ##STR81## ##STR82##X ##STR83## ##STR84## ##STR85## ##STR86## ##STR87## ##STR88## ##STR89## ##STR90## ##STR91##Z CH.sub.2 (CH.sub.2).sub.2 (CH.sub.2).sub.3 (CH.sub.2).sub.4 single bond CH.sub.2 (CH.sub.2).sub.2 single CH.sub.2__________________________________________________________________________
TABLE 8__________________________________________________________________________ ##STR92##__________________________________________________________________________ ##STR93## ##STR94## ##STR95## ##STR96## ##STR97## ##STR98## ##STR99## ##STR100## ##STR101##X ##STR102## ##STR103## ##STR104## ##STR105## ##STR106## ##STR107## ##STR108## ##STR109## ##STR110##Z (CH.sub.2).sub.2 (CH.sub.2).sub.3 (CH.sub.2).sub.4 CH.sub.2 single bond (CH.sub.2).sub.2 (CH.sub.2).sub.3 (CH.sub.2).sub.4 CMe.sub.2__________________________________________________________________________
TABLE 9__________________________________________________________________________ ##STR111##__________________________________________________________________________ ##STR112## ##STR113## ##STR114## ##STR115## ##STR116## ##STR117## ##STR118## ##STR119## ##STR120##Z single bond single bond single bond single bond CH.sub.2 (CH.sub.2).sub.2 CH.sub.2 (CH.sub.2).sub.2 CH.sub.2R.sup. 6' CONH.sub.2 CONH.sub.2 SO.sub.2 NH.sub.2 SO.sub.2 NH.sub.2 CONH.sub.2 CONH.sub.2 SO.sub.2 NH.sub.2 SO.sub. SO.sub.2 NH.sub.2__________________________________________________________________________
TABLE 10__________________________________________________________________________ ##STR121##__________________________________________________________________________R.sup.2 OH OH OH OH OMe OH OH OH OHR.sup.5 H H H H H H Me Et n-Pr ##STR122## ##STR123## ##STR124## ##STR125## ##STR126## ##STR127## ##STR128## ##STR129## ##STR130##Y O O O O single bond single bond single bond single single bondZ CH.sub.2 (CH.sub.2).sub.2 CH.sub.2 (CH.sub.2).sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2R.sup. 6' CONH.sub.2 CONH.sub.2 CONH.sub.2 CONH.sub.2 CONH.sub.2 CO.sub.2 Et CO.sub.2 Et CO.sub.2 Et CO.sub.2__________________________________________________________________________ Et
TABLE 11__________________________________________________________________________ ##STR131##__________________________________________________________________________A CH.sub.2 (CH.sub.2).sub.2 (CH.sub.2).sub.3 (CH.sub.2).sub.4 (CH.sub.2).sub.5 CHMe CH.sub.2 CH.sub.2 CH.sub.2 ##STR132## ##STR133## ##STR134## ##STR135## ##STR136## ##STR137## ##STR138## ##STR139## ##STR140##R.sup.5 i-Pr H H H H H H H HZ CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 (CH.sub.2).sub.2 (CH.sub.2).sub.3__________________________________________________________________________
TABLE 12__________________________________________________________________________ ##STR141##__________________________________________________________________________ ##STR142## ##STR143## ##STR144## ##STR145## ##STR146## ##STR147## ##STR148## ##STR149## ##STR150##X ##STR151## ##STR152## ##STR153## ##STR154## ##STR155## ##STR156## ##STR157## ##STR158## ##STR159##Z CH.sub.2 (CH.sub.2).sub.2 (CH.sub.2).sub.3 CH.sub.2 (CH.sub.2).sub.2 (CH.sub. 2).sub.3 CH.sub.2 CH.sub.2 CH.sub.2__________________________________________________________________________
TABLE 13__________________________________________________________________________ ##STR160##__________________________________________________________________________ ##STR161## ##STR162## ##STR163## ##STR164## ##STR165## ##STR166## ##STR167## ##STR168## ##STR169##X ##STR170## ##STR171## ##STR172## ##STR173## ##STR174## ##STR175## ##STR176## ##STR177## ##STR178##Z CH.sub.2 CH.sub.2 CH.sub.2 (CH.sub.2).sub.2 (CH.sub.2).sub.3 CH.sub.2 (CH.sub.2).sub.2 (CH.sub.2).sub.3 CH.sub.2__________________________________________________________________________
TABLE 14__________________________________________________________________________ ##STR179##__________________________________________________________________________ ##STR180## ##STR181## ##STR182## ##STR183## ##STR184## ##STR185## ##STR186## ##STR187## ##STR188##X ##STR189## ##STR190## ##STR191## ##STR192## ##STR193## ##STR194## ##STR195## ##STR196## ##STR197##Z (CH.sub.2).sub.2 (CH.sub.2).sub.3 CH.sub.2 (CH.sub.2).sub.2 (CH.sub.2).sub.3 CH.sub.2 CH.sub.2 (CH.sub.2).sub.2 (CH.sub.2).sub.2__________________________________________________________________________
TABLE 15__________________________________________________________________________ ##STR198##__________________________________________________________________________ ##STR199## ##STR200## ##STR201## ##STR202## ##STR203## ##STR204## ##STR205## ##STR206## ##STR207##Y O O O O single bond single bond single bond single single bondZ CH.sub.2 CH.sub.2 (CH.sub.2).sub.2 (CH.sub.2).sub.2 single bond CH.sub.2 (CH.sub.2).sub.2 (CH.sub.2).sub.3 (CH.sub.2).sub.4R.sup. 6' CO.sub.2 Et CO.sub.2 Et CO.sub.2 Et CO.sub.2 Et CO.sub.2 H CO.sub.2 H CO.sub.2 H CO.sub.2 H CO.sub.2 H__________________________________________________________________________
TABLE 16__________________________________________________________________________ ##STR208##__________________________________________________________________________ ##STR209## ##STR210## ##STR211## ##STR212## ##STR213## ##STR214## ##STR215## ##STR216## ##STR217##Z (CH.sub.2).sub.5 CH.sub.2 (CH.sub.2).sub.2 CH.sub.2 (CH.sub.2).sub.2 CH.sub.2 (CH.sub.2).sub.2 CH.sub.2 (CH.sub.2).sub.2__________________________________________________________________________
TABLE 17__________________________________________________________________________ ##STR218##__________________________________________________________________________ ##STR219## ##STR220## ##STR221## ##STR222## ##STR223## ##STR224## ##STR225## ##STR226## ##STR227##Z CH.sub.2 (CH.sub.2).sub.2 single bond CH.sub.2 (CH.sub.2).sub.2 (CH.sub.2).sub.3 (CH.sub.2).sub.4 (CH.sub.2).sub.5 single__________________________________________________________________________ bond
TABLE 18__________________________________________________________________________ ##STR228##__________________________________________________________________________R.sup.5 H H H Me Et n-Pr i-Pr n-Bu i-Bu ##STR229## ##STR230## ##STR231## ##STR232## ##STR233## ##STR234## ##STR235## ##STR236## ##STR237##Z CH.sub.2 (CH.sub.2).sub.2 (CH.sub.2).sub.3 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2__________________________________________________________________________
TABLE 19__________________________________________________________________________ ##STR238##__________________________________________________________________________ ##STR239## ##STR240## ##STR241## ##STR242## ##STR243## ##STR244## ##STR245## ##STR246## ##STR247##X ##STR248## ##STR249## ##STR250## ##STR251## ##STR252## ##STR253## ##STR254## ##STR255## ##STR256##Z CH.sub.2 (CH.sub.2).sub.2 CH.sub.2 (CH.sub.2).sub.2 CH.sub.2 (CH.sub.2).sub.2 (CH.sub.2).sub.3 CH.sub.2 (CH.sub.2).sub.2__________________________________________________________________________
TABLE 20__________________________________________________________________________ ##STR257##__________________________________________________________________________ ##STR258## ##STR259## ##STR260## ##STR261## ##STR262## ##STR263## ##STR264## ##STR265## ##STR266##X ##STR267## ##STR268## ##STR269## ##STR270## ##STR271## ##STR272## ##STR273## ##STR274## ##STR275##Z (CH.sub.2).sub.3 CH.sub.2 (CH.sub.2).sub.2 (CH.sub.2).sub.3 CH.sub.2 (CH.sub.2).sub.2 (CH.sub. 2).sub.3 CH.sub.2 (CH.sub.2).sub.2__________________________________________________________________________
TABLE 21__________________________________________________________________________ ##STR276##__________________________________________________________________________ ##STR277## ##STR278## ##STR279## ##STR280## ##STR281## ##STR282## ##STR283## ##STR284## ##STR285## ##STR286## ##STR287## ##STR288## ##STR289## ##STR290## ##STR291## ##STR292## ##STR293## ##STR294## ##STR295## CH.sub.2 (CH.sub.2).sub.2 (CH.sub.2).sub.3 CH.sub.2 (CH.sub.2).sub.2 (CH.sub.2).sub.3 CH.sub.2 (CH.sub.2).sub.2__________________________________________________________________________
TABLE 22__________________________________________________________________________ ##STR296##__________________________________________________________________________ACH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 (CH.sub.2).sub.2 (CH.sub.2).sub.3 ##STR297## ##STR298## ##STR299## ##STR300## ##STR301## ##STR302## ##STR303## ##STR304## ##STR305## ##STR306## ##STR307## ##STR308## ##STR309## ##STR310## ##STR311## ##STR312## ##STR313## ##STR314## ##STR315## CH.sub.2 (CH.sub.2).sub.2 (CH.sub.2).sub.3 CH.sub.2 (CH.sub.2).sub.2 (CH.sub.2).sub.3 CH.sub.2 CH.sub.2__________________________________________________________________________
TABLE 23__________________________________________________________________________ ##STR316##__________________________________________________________________________R.sup.4 Et Et Et Me Et n-Pr n-Bu ##STR317## CH.sub.2 CCHA (CH.sub.2).sub.4 (CH.sub.2).sub.5 CHMe CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2__________________________________________________________________________
TABLE 24__________________________________________________________________________ ##STR318##__________________________________________________________________________R.sup.3 Me Et n-Pr n-Bu n-Pentyl ##STR319## CH.sub.2 CCH Me EtR.sup.4 Et Et Et Et Et Et Et H H__________________________________________________________________________
TABLE 25__________________________________________________________________________ ##STR320##__________________________________________________________________________R.sup.1 Me Me Me Me Me Me Me Et n-PrR.sup.2 OH OH OH OH OMe OEt O-n-Pr OH OHR.sup.3 i-Pr i-Bu n-Bu n-Pentyl H H H H HR.sup.4 H H H H Et Et Et Et Et__________________________________________________________________________
TABLE 26__________________________________________________________________________ ##STR321##__________________________________________________________________________R.sup.1 n-Bu n-Pentyl Me Me MeR.sup.6' CO.sub.2 H CO.sub.2 H ##STR322## ##STR323## ##STR324##__________________________________________________________________________
TABLE 27__________________________________________________________________________ ##STR325##__________________________________________________________________________ ##STR326## ##STR327## ##STR328## ##STR329## ##STR330##R.sup.6' ##STR331## ##STR332## ##STR333## ##STR334## ##STR335##__________________________________________________________________________
TABLE 28__________________________________________________________________________ ##STR336##__________________________________________________________________________ ##STR337## ##STR338## ##STR339## ##STR340## ##STR341##R.sup.6' ##STR342## ##STR343## ##STR344## ##STR345## ##STR346##__________________________________________________________________________
TABLE 29__________________________________________________________________________ ##STR347##__________________________________________________________________________R.sup.6 CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 CO.sub.2 H (CH.sub.2).sub.3 CO.sub.2 H (CH.sub.2).sub.4 CO.sub.2 H CH.sub.2 CO.sub.2 Me__________________________________________________________________________
TABLE 30__________________________________________________________________________ ##STR348##__________________________________________________________________________R.sup.6 CH.sub.2 CO.sub.2 Et ##STR349## ##STR350## ##STR351## ##STR352##__________________________________________________________________________
TABLE 31__________________________________________________________________________ ##STR353##__________________________________________________________________________R.sup.6 ##STR354## ##STR355## ##STR356## ##STR357## ##STR358##__________________________________________________________________________
TABLE 32__________________________________________________________________________ ##STR359##__________________________________________________________________________R.sup.6 ##STR360## ##STR361## ##STR362## ##STR363## ##STR364##__________________________________________________________________________
TABLE 33__________________________________________________________________________ ##STR365##__________________________________________________________________________R.sup.6 ##STR366## ##STR367## ##STR368## ##STR369## ##STR370##__________________________________________________________________________
TABLE 34__________________________________________________________________________ ##STR371##__________________________________________________________________________R.sup.6 ##STR372## ##STR373## CH.sub.2 CONH.sub.2 CH.sub.2 CONHCH.sub.3 CH.sub.2 CONMe.sub.2__________________________________________________________________________
TABLE 35__________________________________________________________________________ ##STR374##__________________________________________________________________________R.sup.6 (CH.sub.2).sub.2 CONH.sub.2 (CH.sub.2).sub.3 CONMe.sub.2 ##STR375## ##STR376## ##STR377##__________________________________________________________________________
TABLE 36__________________________________________________________________________ ##STR378##__________________________________________________________________________R.sup.6 ##STR379## ##STR380## ##STR381## ##STR382## ##STR383##__________________________________________________________________________
TABLE 37__________________________________________________________________________ ##STR384##__________________________________________________________________________ ##STR385## ##STR386## ##STR387## ##STR388## ##STR389## ##STR390##__________________________________________________________________________
TABLE 38______________________________________ ##STR391##______________________________________R.sup.1 Et n-Pr Me Me MeR.sup.2 OH OH OMe OEt OHR.sup.3 H H H H n-PrR.sup.4 Et Et Et Et H______________________________________
TABLE 39__________________________________________________________________________ ##STR392##__________________________________________________________________________R.sup.2 OH OMe OMe OH OHR.sup.3 n-Pr n-Pr n-Pr H HR.sup.4 H H H Et EtA CH.sub.2 CH.sub.2 CH.sub.2 (CH.sub.2).sub.2 CH.sub.2R.sup.5 H H H H MeR.sup.6 ##STR393## ##STR394## (CH.sub.2).sub.2 CO.sub.2 H (CH.sub.2).sub.2 CO.sub.2 H (CH.sub.2).sub.2 CO.sub.2 H__________________________________________________________________________
TABLE 40______________________________________ ##STR395##______________________________________R.sup.5 Et n-Pr isoBu sec-Bu (CH.sub.2).sub.2 OH______________________________________
TABLE 41__________________________________________________________________________ ##STR396##__________________________________________________________________________R.sup.3 H H H H n-PrR.sup.4 Et Et Et Et HR.sup.6 (CH.sub.2).sub.2 CO.sub.2 H ##STR397## ##STR398## ##STR399## ##STR400##__________________________________________________________________________
TABLE 42__________________________________________________________________________ ##STR401##__________________________________________________________________________R.sup.2 OMe OH OH OH OHR.sup.3 n-Pr H H H HR.sup.4 H Et Et Et Et ##STR402## ##STR403## ##STR404## ##STR405## ##STR406##R.sup.6 ##STR407## (CH.sub.2).sub.2 CO.sub.2 H ##STR408## ##STR409## ##STR410##__________________________________________________________________________
TABLE 43__________________________________________________________________________ ##STR411##__________________________________________________________________________R.sup.2 OH OMe OH OH OHR.sup.3 n-Pr n-Pr H H HR.sup.4 H H Et Et Et ##STR412## ##STR413## ##STR414## ##STR415## ##STR416##R.sup.6 ##STR417## ##STR418## (CH.sub.2).sub.2 CO.sub.2 H ##STR419## ##STR420##__________________________________________________________________________
TABLE 44__________________________________________________________________________ ##STR421##__________________________________________________________________________R.sup.2 OH OH OMe OH OHR.sup.3 H n-Pr n-Pr H HR.sup.4 Et H H Et EtR.sup.6 ##STR422## ##STR423## ##STR424## ##STR425## ##STR426##__________________________________________________________________________
TABLE 45__________________________________________________________________________ ##STR427##__________________________________________________________________________R.sup.6 ##STR428## ##STR429## ##STR430## ##STR431## ##STR432##__________________________________________________________________________
TABLE 46__________________________________________________________________________ ##STR433##__________________________________________________________________________R.sup.1 Me Et Me Me MeR.sup.6 (CH.sub.2).sub.2 OH (CH.sub.2).sub.3 OH (CH.sub.2).sub.4 OH ##STR434## ##STR435##__________________________________________________________________________
TABLE 47__________________________________________________________________________ ##STR436##__________________________________________________________________________R.sup.2 OH O-n-Pr OH OH OHR.sup.3 Me H H H HR.sup.4 Me H Et Et EtR.sup.5 H H H Me HR.sup.6 (CH.sub.2).sub.2 CO.sub.2 H (CH.sub.2).sub.2 CO.sub.2 H CH(CH.sub.2 OH).sub.2 CH(CH.sub.2 OH).sub.2 CH.sub.2 CONHCH.sub.2 CO.sub.2 H__________________________________________________________________________
Among the leukotriene B.sub.4 antagonists thus obtained, the compound [I] can be converted to a pharmaceutically acceptable salt form. The pharmaceutically acceptable salts of these leukotriene B.sub.4 antagonists can be formed with pharmaceutically acceptable metal cation such as sodium, potassium, magnesium and calcium, ammonium or amine cations.
The preparations of pharmaceutical compositions can be carried out by conventional methods. For example, leukotriene B.sub.4 antagonists [I] may be mixed with carriers, diluents, lubricants, fillers and/or binders such as lactose, sucrose, calcium phosphate, starch, talcum, casein, magnesium stearate, methyl cellulose, polyglycols, tragacanth and the like, sometimes together with stabilizers and emulsifying agents. The resulting mixture may be processed in a usual manner to tablets, capsules, pills, injections, ointment, suppositories and the like. In a clinical practice, the leukotriene B.sub.4 antagonists [I] can be administered orally, intranasally, intradermally or the like.
The daily dosage may vary depending upon the administration route, symptom, age or weight of the patient, and the usual oral dosage of the active ingredient is between about 1 mg and about 1000 mg daily for human beings.

DESCRIPTION OF THE PREFERRED EMBODIMENTS
Practical and preferred embodiments of the present invention are illustrated in the following examples, which are not intended to limit the scope of the invention.
REFERENCE EXAMPLE 1
5-Ethyl-2,4-dihydroxyacetophenone (0.97 g, 5.0 mmol) and methyl 6-bromomethylpyridine-2-carboxylate (1.38 g, 5.8 mmol) were dissolved in an N,N-dimethylformamide solution (50 ml), and anhydrous potassium carbonate (480 mg) was added to the above solution, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was poured into water and extracted with ethyl acetate (100 ml.times.3).
The extract was dried, concentrated and chromatographed on silica gel to give methyl 6-[(4-acetyl-2-ethyl-5-hydroxyphenoxy)methyl]pyridine-2-carboxylate.
REFERENCE EXAMPLE 2
Methyl 6-[(4-acetyl-2-ethyl-5-hydroxyphenoxy)methyl]pyridine-2-carboxylate (38 mg, 12 mmol) was dissolved in a methanol solution (2 ml), and one normal sodium hydroxide (1 ml) was added to the above solution at 0.degree. C., and the mixture was stirred at room temperature for 1 hour. One-tenth normal potassium bisulfate was titrated to the above solution until it became pH2. Then, precipitated white crystals were separated by filtration, and washed with water, and dried to give 6-[(4-acetyl-2-ethyl-5-hydroxyphenoxy)methyl]pyridine-2-carboxylic acid.
REFERENCE EXAMPLE 3
3-n-Propyl-2,4-dihydroxyacetophenone (816 mg, 4.2 mmol) was added to a methanol solution (10 ml), sodium metal was added to the solution at 0.degree. C., and the mixture was stirred for 30 min, and evaporated under reduced pressure, and dried to give a sodium salt of 3-n-propyl-2,4-dihydroxyacetophenone. The salt was dissolved in N,N-dimethylformamide (10 ml), and it was added to a N,N-dimethylformamide solution (10 ml) of methyl-6-bromomethylpyridine-2-carboxylate (920 mg, 4.0 mmol) at room temperature, and the mixture was stirred for 1 hour.
The reaction mixture was poured into water, and normal potassium bisulfate was titrated until it became pH3, and extracted with ethyl acetate (100 ml.times.3). The extract was dried, concentrated and chromatographed on silica gel to give methyl 6-[(4-acetyl-3-hydroxy-2-n-propylphenoxy)methyl]pyridine-2-carboxylate.
REFERENCE EXAMPLE 4
According to the procedure of Reference Example 2, 6-[(4-acetyl-3-hydroxy-2-n-propylphenoxy)methyl]pyridine-2-carboxylic acid was obtained by hydrolysis of methyl 6-[(4-acetyl-3-hydroxy-2-n-propylphenoxy)methyl]pyridine-2-carboxylate.
REFERENCE EXAMPLE 5
Anhydrous potassium carbonate (1.0 g) was added to a N,N-dimethylformamide solution (10 ml) of methyl 6-[(4-acetyl-2-ethyl-5-hydroxyphenoxy)methyl]pyridine-2-carboxylate (500 mg, 1.4 mmol) and methyliodide (5 ml), and the mixture was stirred at 70.degree. C. for 2 hours.
The reaction mixture was poured into water and extracted with ethylacetate and washed with saturated aqueous sodium chloride. Then, the extract was dried, concentrated and chromatographed on silica gel to give methyl 6-[(4-acetyl-2-ethyl-5-methoxyphenoxy)methyl]pyridine-2-carboxylate.
REFERENCE EXAMPLE 6
According to the procedure of Reference Example 2, 6-[(4-acetyl-2-ethyl-5-methoxyphenoxy)methyl]pyridine-2-carboxylic acid was obtained by hydrolysis of methyl 6-[(4-acetyl-2-ethyl-5-methoxyphenoxy)methyl]pyridine-2-carboxylate.
REFERENCE EXAMPLE 7
According to the procedure of Reference Example 5, methyl 6-[(4-acetyl-2-n-propyl-3-methoxyphenoxy)methyl]pyridine-2-carboxylate was obtained from methyl 6-[(4-acetyl-3-hydroxy-2-n-propylphenoxy)methyl]pyridine-2-carboxylate.
REFERENCE EXAMPLE 8
According to the procedure of Reference Example 2, 6-[(4-acetyl-2-n-propyl-3-methoxyphenoxy)methyl]pyridine-2-carboxylic acid was obtained by hydrolysis of methyl 6-[(4-acetyl-2-n-propyl-3-methoxyphenoxy)methyl]pyridine-2-carboxylate.
REFERENCE EXAMPLE 9
a compound included in formula [XVI]
A mixture of 6-methylpyridine-2-carboxylic acid (13.7 g, 100 mmol) and thionyl chloride (40 ml) was stirred at 70.degree. C. for 1 hour. The mixture was dried, and dichloromethane (40 ml) was added to the residue. The solution was added to a dichloromethane solution of 2-amino-2-methyl-propanol (36.0 g, 400 mmol), and stirred. The mixture was washed with water, and dried over anhydrous magnesium sulfate. The extract was concentrated and chromatographed on silica gel to give an amide compound. 4,4-Dimethyl-2-oxazoline compound was obtained by reacting the amide compound and thionyl chloride in dichloromethane. 4,4-Dimethyl-2-oxazoline compound was reacted with n-butyl lithium at -78.degree. C. in anhydrous tetrahydrofuran, and chloroethyl phenyl ether (782 mg, 5 mmol) was added. Purified alkylated compound was treated with ethanol saturated with HCl to give ethyl 6-(3-chloropropyl)pyridine-2-carboxylate.
REFERENCE EXAMPLE 10
a compound included in formula [II]
According to the procedure of Reference Examples 1,2, 6-[3-(4-acetyl-2-ethyl-5-hydroxyphenoxy)propyl]pyridine-2-carboxylic acid was obtained from ethyl 6-(3-chloropropyl)pyridine-2-carboxylate and 5-ethyl-2,4-dihydroxyacetophenone.
TABLE 48______________________________________ ##STR437##2 ##STR438##3 ##STR439##4 ##STR440##______________________________________
TABLE 49______________________________________ .sup.1 H-NMR .delta. ppm______________________________________1 (solvent:CDCL.sub.3) 0.99(3H, J=7.4Hz), 1.62(2H, tq, J=7.4Hz, J=7.4Hz), 2.57(3H, s), 2.76(2H, t, J=7.4Hz), 4.04(3H, s), 5.39(2H, s), 6.46(1H, d, J=8.9Hz), 7.59(1H, d, J=8.9Hz), 7.79(1H, d, J=6.6Hz), 7.92(1H, dd, J=6.6Hz, J=7.9Hz), 8.10(1H, d, J=7.9Hz)2 (solvent:CDCL.sub.3) 1.26(3H, t, J=7.6Hz), 2.59(3H, S), 2.68(2H, q, J=7.6Hz), 5.30(2H, s), 6.43(1H, s), 7.51(1H, s), 7.78(1H, d, J=6.9Hz), 8.04(1H, dd, J=6.9Hz, J=7.9Hz), 8.22(1H, d, J=7.9Hz)3 (solvent:CDCL.sub.3) 0.99(3H, t, J=7.4Hz), 1.62(2H, tq, J=7.4Hz, J=7.4Hz), 2.57(3H, s), 2.76(2H, t, J=7.4Hz), 4.04(3H, s), 5.39(2H, s), 6.46(1H, d, J=8.9Hz), 7.59(1H, d, J=8.9Hz), 7.79(1H, d, J=6.6Hz), 7.92(1H, dd, J=6.6Hz, J=7.9Hz), 8.10(1H, d, J=7.9Hz)4 (solvent:CDCL.sub.3) 0.99(3H, t, J=7.4Hz), 1.62(2H, tq, J=7.4Hz, J=7.4Hz), 2.57(3H, s), 2.76(2H, t, J=7.4Hz), 5.34(2H, s), 6.45(1H, d, J=8.9Hz), 7.60(1H, d, J=8.9Hz), 7.79(1H, dd, J=1.0Hz, J=6.9Hz), 8.04(1H, dd, J=6.9Hz, J=7.4Hz), 8.21(1H, dd, J=1.0Hz, J= 7.4Hz)______________________________________
TABLE 50______________________________________ ##STR441##6 ##STR442##7 ##STR443##8 ##STR444##______________________________________
TABLE 51______________________________________ .sup.1 H-NMR .delta. ppm______________________________________5 (solvent:CDCL.sub.3) 1.24(3H, t, J=7.6Hz), 2.58(3H, s), 2.70(2H, q, J=7.6Hz), 3.86(3H, s), 4.04(3H, s), 5.40(2H, s), 7.72(1H, s), 7.79(1H, d, J=7.9Hz), 7.94(1H, dd, J=7.9Hz), J=7.6Hz), 8.11(1H, d, J=7.6Hz)6 (solvent:CDCL.sub.3) 1.24(3H, t, J=7.4Hz), 2.57(3H, s), 2.69(2H, q, J=7.4Hz), 3.90(3H, s), 5.40(2H, s), 6.64(1H, s), 7.65(1H, s), 7.80(1H, d, J=7.3Hz), 8.01(1H, dd, J=7.6Hz, J=7.6Hz), 8.13(1H, d, J=7.9Hz)7 (solvent:CDCL.sub.3) 1.02(3H, t, J=7.5Hz), 1.66(2H, q, J=7.6Hz), 2.61(3H, s), 2.75(2H, t, J=7.8Hz), 3.78(3H, s), 5.31(2H, s), 6.70(1H, d, J=8.6Hz), 7.56(1H, d, J=8.9Hz), 7.90(1H, d, J=7.9Hz), 8.04(1H, dd, J=7.6Hz, J=7.9Hz), 8.21(1H, d, J=7.6Hz)8 (solvent:CDCL.sub.3) 1.02(3H, t, J=7.6Hz), 1.65(2H, q, J=7.7Hz), 2.62(3H, s), 2.75(2H, t, J=7.8Hz), 3.78(3H, s), 5.31(2H, s), 6.70(1H, d, J=8.6Hz), 7.56(1H, d, J=8.9Hz), 7.90(1H, d, J=7.9Hz), 8.04(1H, dd, J=7.6Hz, J=7.9Hz), 8.21(1H, d, J=7.6Hz)______________________________________
EXAMPLE 1
A mixture of 6-[(4-acetyl-2-ethyl-5-hydroxyphenoxy)methyl]pyridine-2-carboxylic acid (63 mg, 0.20 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (40 mg, 0.20 mmol), 1-hydroxybenzotriazole (30 mg, 0.22 mmol), 2-aminothiazole-4-carboxamide (35 mg, 0.24 mg) and triethylamine (20 mg, 0.20 mmol) in a mixed solution of dichloromethane (2 ml) and N,N-dimethylformamide (2 ml) was stirred at room temperature for 44 hours. The reaction mixture was poured into water and extracted with ethyl acetate (80 ml.times.3). The extract was dried over anhydrous magnesium sulfate, concentrated under reduced pressure and chromatographed on silica gel to give 2-[6-[(4-acetyl-2-ethyl-5-hydroxyphenoxy)methyl]pyridine-2-carboxamide]thiazol-4-ylcarboxamide.
EXAMPLE 2.about.35,62,88,90,92
According to the procedure of Example 1, the compounds (Example 2.about.35,62,88,90,92) were obtained.
EXAMPLE 36
Ethyl 2-[6-[(4-acetyl-2-ethyl-5-hydroxyphenoxy)methyl]pyridine-2-carboxamide]thiazole-4-ylcarboxylate (24 mg, 0.05 mmol) was suspended in methanol (1.5 ml), followed by addition of one-second normal sodium hydroxide (1.0 ml).
After the solution was stirred for 2 hr, it was made acidic with one-second normal potassium bisulfate. Precipitated crystals were separated by filtration, and washed with water, and dried to give 2-[6-[(4-acetyl-2-ethyl-5-hydroxyphenoxy)methyl]pyridine-2-carboxamide]thiazol-4-ylcarboxylic acid.
EXAMPLE 37.about.52,61,87,89,91
According to the procedure of Example 36, the compounds (Example 37.about.52, 61, 87, 89, 91) were obtained.
EXAMPLE 54.about.56,64,67,68,70,72,74,76,78,80,82,84,86,94,96,100, 102,104,106,108,112,114,115,116-121,123,126,127,138,141
According to the procedure of Example 1, the title compounds were obtained.
EXAMPLE 53,57.about.60,63,65,69,71,73,75,77,79,81,83,85,93,95,99, 101,105,107,111,113,122,130
According to the procedure of Example 36, the title compounds were obtained.
EXAMPLE 98
Ethyl 2-[6-[(4-acetyl-2-ethyl-5-hydroxyphenoxy)methyl]pyridine-2-carboxamide]pyridine-6-ylcarboxylate (280 mg, 0.60 mM) was dissolved in dichloromethane (5 ml), followed by addition of m-chloroperbenzoic acid (124 mg, 0.72 mM). After being stirred at room temperature for 16 hours, the reaction mixture was washed with aqueous sodium sulfite-sodium bicarbonate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give ethyl 2-[6-[(4-acetyl-2-ethyl-5-hydroxyphenoxy)methyl]pyridine-2-carboxamide]pyridine-N-oxide-6-ylcarboxylate.
EXAMPLE 110,125,129,131,134,136,139,142
According to the procedure of Example 98, the title compounds were obtained.
EXAMPLE 97,109,124,128,132,133,135,137,140
According to the procedure of Example 36, the title compounds were obtained.
EXAMPLE 143.about.178,212,214,216,218,222,225,226
According to the procedure of Example 1, the title compounds were obtained.
EXAMPLE 179.about.211,213,215,223,224
According to the procedure of Example 36, the title compounds were obtained.
TABLE 52______________________________________Ex. No. Structural formula______________________________________ ##STR445##2 ##STR446##3 ##STR447##4 ##STR448##5 ##STR449##______________________________________
TABLE 53______________________________________ .sup.1 H-NMR .delta. ppm______________________________________1 (solvent:CDCL.sub.3) 1.28(3H, t, J=7.6Hz), 2.60(3H, s), 2.71(2H, q, J=7.6Hz), 5.34(1H, s), 5.55(1H, bs), 6.48(1H, s), 7.05(1H, bs), 7.52(1H, s), 7.77(1H, d, J=7.3Hz), 9.90(1H, s), 8.04(1H, dd, J=6.6Hz, J=7.3Hz), 8.28(1H, d, J=7.3Hz), 10.98(1H, bs), 12.70(1H, s)2 (solvent:CDCL.sub.3) 1.27(3H, t, J=7.6Hz), 2.59(3H, s), 2.70(2H, q, J=7.6Hz), 3.69(2H, s), 5.32(2H, s), 5.43(1H, bs), 6.45(1H, s), 6.60(1H, bs), 6.86(1H, s), 7.51(1H, s), 7.74(1H, d, J=6.9Hz), 8.02(1H, t, J=6.9Hz), 8.27(1H, d, J=6.9Hz), 12.68(1H, s)3 (solvent:CDCL.sub.3) 1.26(3H, t, J=7.6Hz), 2.58(3H, s), 2.69(2H, q, J=7.6Hz), 3.70(2H, s), 3.81(3H, s), 5.39(1H, s), 5.43(1H, bs), 6.46(1H, s), 6.70(1H, bs), 6.88(1H, s), 7.49(1H, s), 7.64(1H, dd, J=1.0Hz, J=7.9Hz), 7.79(1H, dd, J=7.6Hz, J=7.9Hz), 7.95(1H, dd, J=1.0Hz, J=7.6Hz), 12.65(1H, s)4 (solvent:CDCL.sub.3) 1.26(3H, t, J=7.6Hz), 1.44(3H, t, J=6.9Hz), 2.58(3H, s), 2.69(2H, q, J=7.6Hz), 3.69(2H, S), 4.36(2H, q, J=6.9Hz) 5.25(1H, s), 5.44(1H, bs), 6.43(1H, s), 6.67(1H, bs), 6.89(1H, s), 7.49(1H, s), 7.64(1H, d, J=7.9Hz), 7.74(1H, d, J=6.9Hz), 7.94(1H, dd, J=6.9Hz, J=7.9Hz), 12.66(1H, s)5 (solvent:CDCL.sub.3) 0.78(6H, d, J=6.6Hz), 1.26(3H, t, J=7.6Hz), 2.0-2.2(1H, m), 2.58(3H, s), 2.68(2H, q, J=7.6Hz), 3.66(2H, s), 4.33(2H, d, J=7.3Hz), 5.21(2H, s), 5.84(1H, bs), 6.42(1H, s), 6.60(1H, bs), 6.88(1H, s), 7.49(1H, s), 7.62(1H, d, J=7.6Hz), 7.74(1H, d, J=7.9Hz), 7.93(1H, dd, J=7.6Hz, J=7.9Hz), 12.66(1H, s)______________________________________
TABLE 54______________________________________Ex.No. Structural formula______________________________________ ##STR450##7 ##STR451##8 ##STR452##9 ##STR453##10 ##STR454##______________________________________
TABLE 55______________________________________ .sup.1 H-NMR .delta. ppm______________________________________6 (solvent:CDCL.sub.3) 1.28(3H, t, J=7.6Hz), 2.59(3H, s), 2.70(2H, q, J=7.6Hz), 2.84(3H, d, J=5.0Hz), 3.67(2H, s), 5.33(2H, s), 6.45(1H, s), 6.48(1H, bs), 6.85(1H, s), 7.51(1H, s), 7.74(1H, d, J=6.6Hz), 8.02(1H, t, J=6.6Hz), 8.27(1H, d, J=6.6Hz), 11.06(1H, bs), 12.70(1H, s)7 (solvent:CDCL.sub.3) 1.27(3H, t, J=7.6Hz), 2.59(3H, s), 2.70(2H, q, J=7.6Hz), 3.01(3H, s), 3.11(1H, s), 3.83(2H, s), 5.28(2H, s), 6.43(1H, s), 6.86(1H, b), 7.51(1H, s), 7.72(1H, dd, J=1.0Hz, J=7.9Hz), 8.00(1H, t, J=7.9Hz), 8.25(1H, dd, J=1.0Hz, J=7.9Hz), 11.08(1H, bs), 12.70(1H, s)8 (solvent:CDCL.sub.3) 1.15(6H, d, J=6.6Hz), 1.27(3H, t, J=7.6Hz), 2.59(3H, s), 2.70(2H, q, J=7.6Hz), 3.63(2H, s), 4.0-4.2(1H, m), 5.32(1H, s), 6.06(1H, bs), 6.45(1H, s), 6.85(1H, s), 7.51(1H, s), 7.74(1H, d, J=7.9Hz), 8.02(1H, t, J=7.9Hz), 8.27(1H, d, J=7.9Hz), 11.06(1H, bs), 12.70(1H, s)9 (solvent:CDCL.sub.3) 1.27(3H, t, J=7.6Hz), 1.31(3H, s), 1.34(3H, s), 2.59(3H, s), 2.70(2H, q, J=7.6Hz), 3.1-3.2(1H, m), 5.30(2H, s), 6.44(1H, s), 6.62(1H, s), 7.51(1H, s), 7.71(1H, d, J=7.9Hz), 7.99(1H, dd, J=6.6Hz, J=7.9Hz), 8.26(1H, d, J=6.6Hz), 11.05(1H, bs), 12.67(1H, s)10 (solvent:CDCL.sub.3) 1.23(3H, t, J=7.6Hz), 2.60(3H, s), 2.65(2H, q, J=7.6Hz), 5.49(2H, s), 6.64(1H, s), 7.35-7.55(2H, m), 7.6-7.8(3H, m), 8.0-8.3(5H, m), 10.59(1H, bs), 12.60(1H, s)______________________________________
TABLE 56______________________________________Ex. No. Structural formula______________________________________11 ##STR455##12 ##STR456##13 ##STR457##14 ##STR458##15 ##STR459##______________________________________
TABLE 57______________________________________ .sup.1 H-NMR .delta. ppm______________________________________11 (solvent:CDCL.sub.3) 1.22(3H, t, J=7.6Hz), 2.58(3H, s), 2.67(2H, q, J=7.6Hz), 5.49(1H, s), 6.64(1H, s), 7.53(1H, bs), 7.71(1H, s), 7.80-7.85(1H, m), 8.1-8.4(5H, m), 8.85-8.90(1H, m), 10.63(1H, bs), 12.56(1H, s)12 (solvent:CDCL.sub.3) 1.20(3H, t, J=7.6Hz), 2.58(2H, s), 2.64(2H, q, J=7.6Hz), 5.47(2H, s), 6.62(1H, s), 7.30(2H, s), 7.71(1H, s), 7.75-7.90(3H, m), 8.0-8.2(4H, m), 10.75(1H, bs), 12.56(1H, s)13 (solvent:CDCL.sub.3) 1.00(3H, t, J=7.4Hz), 1.63(2H, tq, J=7.4Hz, J=7.4Hz), 2.58(3H, s), 2.77(2H, t, J=7.4Hz), 3.69(2H, s), 5.36(2H, s), 5.40(1H, bs), 6.47(1H, d, J=9.2Hz), 6.50(1H, bs), 6.87(1H, s), 7.62(1H, d, J=9.2Hz), 7.76(1H, d, J=7.9Hz, 8.02(1H, dd, J=7.9Hz, J=7.9Hz), 8.26(1H, d, J=7.9Hz)14 (solvent:CDCL.sub.3) 1.27(3H, t, J=7.6Hz) 1.43(3H, t, J=7.1Hz), 2.59(3H, s), 2.70(2H, q, J=7.6Hz), 4.45(2H, q, J=7.1Hz), 5.28(1H, s), 6.43(1H, s), 7.52(1H, s), 7.73(1H, d, J=7.9Hz), 7.94(1H, d, J=0.7Hz), 8.01(1H, t, J=7.9Hz), 8.25(1H, d, J=7.9Hz), 11.32(1H, bs), 12.66(1H, s)15 (solvent:CDCL.sub.3 ) 1.27(3H, t, J=7.6Hz), 1.30(3H, t, J=7.3Hz), 2.59(3H, s), 2.70(2H, q, J=7.6Hz), 3.76(2H, d, J=0.7Hz), 4.22(2H, q, J=7.3Hz), 5.28(1H, s), 6.43(1H, s), 6.90(1H, d, J=0.7Hz), 7.51(1H, s), 7.72(1H, d, J=7.9Hz), 8.00(1H, dd, J=7.6Hz, J=7.9Hz), 8.25(1H, d, J=7.6Hz), 11.11(1H, bs), 12.67(1H, s)______________________________________
TABLE 58__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________16 ##STR460##17 ##STR461##18 ##STR462##19 ##STR463##20 ##STR464##__________________________________________________________________________
TABLE 59______________________________________ .sup.1 H-NMR .delta. ppm______________________________________16 (solvent:CDCL.sub.3) 1.25(3H, t, J=7.3Hz), 1.27(3H, t, J=7.4Hz), 2.59(3H, s), 2.65-2.80(4H, m), 3.05(2H, t, J=7.3Hz), 4.15(2H, q, J=7.3Hz), 5.30(2H, s), 6.44(1H, s), 6.69(1H, s), 7.51(1H, s), 7.71(1H, d, J=7.7Hz), 7.97(1H, t, J=7.7Hz), 8.24(1H, d, J=7.7Hz), 11.05(1H, bs), 12.67(1H, s)17 (solvent:CDCL.sub.3) 1.27(3H, t, J=7.6Hz), 1.43(3H, t, J=7.1Hz), 2.59(3H, s), 2.70(2H, q, J=7.6Hz), 4.45(2H, q, J=7.1Hz), 5.28(1H, s) 6.43(1H, s), 7.52(1H, s), 7.73(1H, d, J=7.9Hz), 7.94(1H, d, J=0.7Hz), 8.01(1H, t, J=7.9Hz), 8.25(1H, d, J=7.9Hz), 11.32(1H, bs), 12.66(1H, s)18 (solvent:CDCL.sub.3) 1.26(3H, t, J=7.6Hz), 1.28(3H, t, J=7.1Hz), 1.40(3H, t, J=6.9Hz), 2.58(3H, s), 2.69(2H, q, J=7.6Hz), 3.76(2H, d, J=0.7Hz), 4.20(2H, q, J=7.1Hz), 4.32(2H, q, J=6.9Hz), 5.25(1H, s), 6.44(1H, s), 6.92(1H, s), 7.49(1H, s), 7.62(1H, d, J=7.6Hz), 7.70(1H, d, J=6.9Hz), 7.92(1H, dd, J=6.9Hz, J=7.6Hz), 12.65(1H, s)19 (solvent:CDCL.sub.3) 0.76(6H, d, J=6.6Hz), 1.26(3H, t, J=7.6Hz), 1.27(3H, t, J= 7.1Hz), 2.0-2.2(1H, m), 2.58(3H, s), 2.68(2H, q, J=7.6Hz), 3.74(2H, s), 4.18(2H, d, J=7.1Hz), 4.28(2H, d, J=6.9Hz), 5.21(2H, s), 6.43(1H, s), 6.91(1H, s), 7.49(1H, s), 7.58(1H, d, J=7.9Hz), 7.71(1H, d, J=7.9Hz), 7.90(1H, t, J=7.9Hz), 12.63(1H, s)20 (solvent:CDCL.sub.3) 1.27(3H, t, J=7.4Hz), 1.29(3H, t, J=7.3Hz), 2.33(3H, s), 2.59(3H, s), 2.69(2H, q, J=7.4Hz), 3.73(2H, s), 4.20(2H, q, J=7.3Hz), 5.27(2H, s), 6.43(1H, s), 7.51(1H, s), 7.71(1H, d, J=7.9Hz), 7.99(1H, t, J=7.9Hz), 8.24(1H, d, J=7.9Hz), 10.98(1H, bs), 12.67(1H, s)______________________________________
TABLE 60__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________21 ##STR465##22 ##STR466##23 ##STR467##24 ##STR468##25 ##STR469##__________________________________________________________________________
TABLE 61______________________________________ .sup.1 H-NMR .delta. ppm______________________________________21 (solvent:CDCL.sub.3) 1.27(3H, t, J=6.7Hz), 1.32(3H, t, J=7.1Hz), 2.59(3H, s), 2.71(2H, J=7.1Hz), 4.16(2H, s), 4.27(2H, q, J=7.6Hz) 5.32(2H, s), 6.44(1H, s), 7.52(1H, s), 7.75(1H, d, J=7.6Hz), 8.02(1H, t, J=7.6Hz), 8.26(1H, d, J=7.6Hz), 11.21(1H, bs), 12.67(1H, s)22 (solvent:CDCL.sub.3) 1.27(3H, t, J=7.4Hz), 2.58(3H, s), 2.70(2H, q, J=7.4Hz), 2.93(2H, t, J=7.3Hz), 3.40(2H, t, J=7.3Hz), 3.73(3H, s), 5.32(2H, s), 6.43(1H, s), 7.51(1H, s), 7.75(1H, d, J=7.9Hz), 8.01(1H, t, J=7.9Hz), 8.24(1H, d, J=7.9Hz), 11.18(1H, bs), 12.66(1H, s)23 (solvent:CDCL.sub.3) 1.27(3H, t, J=7.3Hz), 1.27(3H, t, J=7.3Hz), 2.59(3H, s), 2.70(2H, q, J=7.3Hz), 3.66(2H, s), 4.17(2H, q, J=7.3Hz) 5.32(2H, s), 6.52(1H, s), 7.0-7.1(1H, m), 7.3-7.4(1H, m), 7.51(1H, s), 7.65-7.7(2H, m), 7.97(1H, t, J=7.7Hz), 8.26(1H, dd, J=1.0Hz, J=7.7Hz), 9.92(1H, bs), 12.68(1H, s)24 (solvent:CDCL.sub.3) 1.26(3H, t, J=7.1Hz), 1.27(3H, t, J=7.6Hz), 2.59(3H, s), 2.70(2H, q, J=7.6Hz), 3.62(2H, s), 4.16(2H, q, J=7.1Hz) 5.32(2H, s), 6.51(1H, s), 7.32(1H, d, J=8.6Hz), 7.51(1H, s), 7.67(1H, d, J=7.3Hz), 7.75(1H, d, J=8.6Hz), 7.98(1H, dd, J=7.3Hz, J=7.6Hz), 8.27(1H, d, J=7.6Hz), 9.90(1H, bs), 12.68(1H, s)25 (solvent:CDCL.sub.3) 1.28(3H, t, J=7.6Hz), 1.29(3H, t, J=7.3Hz), 2.59(3H, s), 2.71(2H, q, J=7.6Hz), 3.80(2H, s), 4.21(2H, q, J=7.3Hz) 5.34(2H, s), 6.47(1H, s), 7.09(1H, d, J=6.9Hz), 7.51(1H, s), 7.65-7.85(2H, m), 7.97(1H, t, J=7.6Hz), 8.26(1H, t, J=7.6Hz), 8.30(1H, t, J=7.6Hz), 10.37(1H, bs), 12.66(1H, s)______________________________________
TABLE 62__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________26 ##STR470##27 ##STR471##28 ##STR472##29 ##STR473##30 ##STR474##__________________________________________________________________________
TABLE 63______________________________________ .sup.1 H-NMR .delta. ppm______________________________________26 (solvent:CDCL.sub.3) 1.25(3H, t, J=7.3Hz), 1.30(3H, t, J=7.3Hz), 2.59(3H, s), 2.71(2H, q, J=7.5Hz), 3.77(2H, s), 3.92(3H, s), 4.22(2H, q, J=7.5Hz), 5.32(2H, s), 6.50(1H, s), 6.91(1H, s), 7.73(1H, s), 7.80(1H, d, J=7.6Hz), 8.03(1H, dd, J=7.9Hz, J=7.6Hz), 8.24(1H, d, J=7.6Hz), 11.18(1H, s)27 (solvent:CDCL.sub.3) 1.26(3H, t, J=7.6Hz), 1.28(3H, t, J=7.4Hz), 2.59(3H, s), 2.72(2H, q, J=7.5Hz), 3.80(2H, s), 3.92(3H, s), 4.21(2H, q, J=7.5Hz), 5.38(2H, s), 6.57(1H, s), 7.10(1H, dd, J=7.0Hz, J=0.7Hz), 7.73(1H, s), 7.76(1H, dd, J=8.3Hz, J=7.9Hz), 7.77(1H, dd, J=7.9Hz, J=1.0Hz), 8.00(1H, dd, J=7.6Hz, J=7.9Hz), 8.27(1H, dd, J=7.9Hz, J=1.0Hz), 8.37(1H, d, J=8.3Hz), 10.40(1H, s)28 (solvent:CDCL.sub.3) 1.00(3H, t, J=7.4Hz), 1.30(3H, t, J=7.1Hz), 1.63 (2H, tq, J=7.9Hz, J=7.3Hz), 2.58(3H, s), 2.77(2H, t, J=7.6Hz), 3.77(2H, s), 4.22(2H, q, J=7.0Hz), 5.32(1H, s) 6.46(1H, d, J=8.9Hz), 6.91(1H, s), 7.62(1H, d, J=8.9Hz), 7.74(1H, d, J=7.9Hz), 8.00(1H, dd, J=7.6Hz, J= 7.9Hz), 8.24(1H, dd, J=7.6Hz, J=0.6Hz)29 (solvent:CDCL.sub.3) 1.00(3H, t, J=7.4Hz), 1.29(3H, t, J=7.2Hz), 1.64(2H, tq, J=7.6Hz, J=7.2Hz), 2.58(3H, s), 2.78(2H, t, J=7.2Hz), 3.81(2H, s), 4.21(2H, q, J=7.0Hz), 5.38(2H, s), 6.50(1H, d, J=8.9Hz), 7.10(1H, dd, J=7.3Hz, J=0.7Hz), 7.62(1H, d, J=8.9Hz), 7.70(1H, d, J=7.9Hz), 7.76(1H, dd, J=8.0Hz, J=7.9Hz), 7.97(1H, dd, J=7.9Hz, J=7.6Hz), 8.25(1H, d, J=6.9Hz), 8.36(1H, d, J=7.6Hz)30 (solvent:CDCL.sub.3) 1.03(3H, t, J=7.3Hz), 1.64(2H, tq, J=7.6Hz, J=7.8Hz), 2.59(3H, s), 2.74(2H, t, J=8.0Hz), 3.78(3H, s), 3.82(2H, s), 5.31(2H, s), 6.71(1H, d, J=8.9Hz), 6.83(1H, s), 7.53(1H, d, J=8.9Hz), 7.70(1H, d, J=7.6Hz), 7.97(1H, dd, J=7.6Hz, J=7.9Hz), 8.19(1H, d, J=7.6Hz)______________________________________
TABLE 64__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________31 ##STR475##32 ##STR476##33 ##STR477##34 ##STR478##35 ##STR479##__________________________________________________________________________
TABLE 65______________________________________ .sup.1 H-NMR .delta. ppm______________________________________31 (solvent:CDCL.sub.3) 1.03(3H, t, J=7.3Hz), 1.65(2H, tq, J=7.6Hz, J=7.9Hz), 2.63(3H, s), 2.76(2H, t, J=7.6Hz), 3.79(3H, s), 3.90(2H, s), 5.37(2H, s), 6.81(1H, d, J=8.6Hz), 7.06(1H, d, J=7.6Hz), 7.59(1H, d, J=8.9Hz), 7.75(1H, d, J=6.9Hz), 7.83(1H, dd, J=7.9Hz, J=7.9Hz), 8.01(1H, dd, J=7.9Hz, J=7.9Hz), 8.28(1H, d, J=6.9Hz), 8.37(1H, d, J=7.9Hz)32 (solvent:CDCL.sub.3) 1.27(3H, t, J=7.6Hz), 1.28(3H, t, J=7.1Hz), 2.59(3H, s), 2.71(2H, q, J=7.6Hz), 3.72(2H, s), 4.17(2H, q, J=7.3Hz) 5.32(2H, s), 6.43(1H, s), 6.89(1H, s), 7.51(1H, s), 7.67(1H, dd, J=0.7Hz, J=8.2Hz), 8.29(1H, dd, J=2.3Hz, J=8.2Hz), 9.14(1H, dd, J=0.7Hz, J=2.3Hz), 9.58(1H, bs), 12.66(1H, s)33 (solvent:CDCL.sub.3) 1.27(3H, t, J=7.6Hz), 1.32(3H, t, J=7.3Hz), 2.59(3H, s), 2.70(2H, q, J=7.6Hz), 4.30(2H, q, J=7.3Hz), 4.68(2H, s) 5.32(2H, s), 6.51(1H, s), 6.70- 6.80(1H, m), 7.25-7.35(2H, m) 7.51(1H, s), 7.55-7.65(1H, m), 7.68(1H, d, J=7.6Hz), 7.98(1H, dd, J=6.6Hz, J=7.6Hz), 8.26(1H, d, J= 6.6Hz), 9.90(1H, bs), 12.67(1H, s)34 (solvent:CDCL.sub.3) 1.27(3H, t, J=7.6Hz), 1.31(3H, t, J=7.3Hz), 2.59(3H, s), 2.70(2H, q, J=7.6Hz), 4.26(2H, q, J=7.3Hz), 4.63(2H, s) 5.31(2H, s), 6.51(1H, s), 6.96(2H, d, J=9.1Hz), 7.51(1H, s), 7.66(1H, d, J=8.6Hz), 7.71(2H, d, J=9.1Hz), 7.97(1H, dd, J=7.6Hz, J=8.6Hz), 8.26(1H, d, J=7.6Hz), 9.82(1H, s), 12.67(1H, s)35 (solvent:CDCL.sub.3) 1.27(3H, t, J=7.3Hz), 1.27(3H, t, J=7.3Hz), 2.59(3H, s), 2.70(2H, q, J=7.6Hz), 3.73(2H, s), 4.07(2H, d, J=5.3Hz) 4.20(2H, q, J=7.3Hz), 5.32(2H, s), 6.45(1H, s), 6.88(1H, s), 7.03(1H, b), 7.51(1H, s), 7.74(1H, dd, J=1.0Hz, J=7.6Hz), 8.01(1H, dd, J=7.6Hz, J=7.9Hz), 8.25(1H, dd, J=1.0Hz, J=7.9Hz), 11.08(1H, bs), 12.67(1H, s)______________________________________
TABLE 66__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________36 ##STR480##37 ##STR481##38 ##STR482##39 ##STR483##40 ##STR484##__________________________________________________________________________
TABLE 67______________________________________ .sup.1 H-NMR .delta. ppm______________________________________36 (solvent:DMSO-d.sub.6) 1.20(3H, J=7.6Hz), 2.59(3H, s), 2.63(2H, q, J=7.6Hz), 5.44(2H, s), 6.71(1H, s), 7.45(1H, s), 7.66(1H, S), 7.7-7.8(1H, m), 8.10-8.20(2H, m), 12.60(1H, bs)37 (solvent:DMSO-d.sub.6) 1.21(3H, t, J=7.6Hz), 2.58(3H, s), 2.65(2H, q, J=7.6Hz), 3.67(2H, s), 5.46(2H, s), 6.63(1H, s), 7.11(1H, s), 7.70(1H, s), 7.78(1H, dd, J=1.3Hz, J=7.3Hz), 12.04(1H, bs), 12.55(1H, s)38 (solvent:DMSO-d.sub.6) 1.21(3H, t, J=7.4Hz), 2.59(3H, s), 2.55-2.75(4H, m), 2.89(2H, t, J=7.6Hz), 5.47(2H, s), 6.63(1H, s), 6.95(1H, s), 7.70(1H, s), 7.78(1H, d, J=7.3Hz), 8.10-8.20(2H, m), 11.94(1H, bs), 12.57(1H, s)39 (solvent:DMSO-d.sub.6) 1.21(3H, t, J=7.4Hz), 2.58(3H, s), 2.65(2H, q, J=7.4Hz), 4.15(2H, s), 5.47(2H, s), 6.63(1H, s), 7.70(1H, s), 7.80(1H, d, J=6.9Hz), 8.10-8.20(2H, m), 12.50(1H, bs), 12.56(1H, s)40 (solvent:DMSO-d.sub.6) 1.21(3H, t, J=7.4Hz), 2.59(3H, s), 2.55-2.75(4H, m), 2.89(2H, t, J=7.6Hz), 5.47(2H, s), 6.63(1H, s), 6.95(1H, s), 7.70(1H, s), 7.78(1H, d, J=7.3Hz), 8.10-8.20(2H, m), 11.94(1H, bs), 12.57(1H, s)______________________________________
TABLE 68__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________41 ##STR485##42 ##STR486##43 ##STR487##44 ##STR488##45 ##STR489##__________________________________________________________________________
TABLE 69______________________________________ .sup.1 H-NMR .delta. ppm______________________________________41 (solvent:DMSO-d.sub.6) 1.20(3H, t, J=7.6Hz), 2.58(3H, s), 2.65(2H, q, J=7.6Hz), 3.58(1H, s), 5.47(2H, s), 6.63(1H, s), 7.04(1H, d, J=7.9Hz), 7.33(1H, m), 7.7-7.8(4H, m), 8.1-8.2(2H, m), 10.41(1H, s), 12.56(1H, s)42 (solvent:DMSO-d.sub.6) 1.20(3H, t, J=7.6Hz), 2.58(3H, s), 2.65(2H, q, J=7.6Hz), 5.46(2H, s), 6.62(1H, s), 7.27(2H, d, J=8.2Hz) 7.65-7.85(4H, m), 8.05-8.20(2H, m), 8.10-8.20(2H, m), 10.40(1H, s) 12.56(1H, bs)43 (solvent:DMSO-d.sub.6) 1.23(3H, t, J=7.6Hz), 2.58(3H, s), 2.67(2H, q, J=7.6Hz), 3.71(2H, s), 5.49(2H, s), 6.65(1H, s), 7.17(1H, d, J=6.9Hz), 7.69(1H, s), 7.75-7.95(2H, m), 8.10-8.20(3H, m), 10.33(1H, s), 12.55(1H, bs)44 (solvent:CDCL.sub.3) 1.25(3H, t, J=7.4Hz), 2.57(3H, s), 2.70(2H, q, J=7.2Hz), 3.83(2H, s), 3.89(3H, s), 5.35(2H, s), 6.52(1H, s), 6.88(1H, s), 7.70(1H, s), 7.81(1H, d, J=7.6Hz), 8.03(1H, dd, J=7.9Hz, J=7.6Hz), 8.24(1H, d, J=7.6Hz)45 (solvent:CDCL.sub.3) 1.26(3H, t, J=6.7Hz), 2.59(3H, s), 2.72(2H, q, J=6.9Hz), 3.91(2H, s), 3.93(3H, s), 5.39(2H, s), 6.55(1H, s), 7.07(1H, d, J=7.3Hz), 7.74(1H, s), 7.83(1H, d, J=6.6Hz) 7.86(1H, dd, J=7.8Hz, J=7.6Hz), 8.04(1H, dd, J=7.9Hz, J=7.9Hz), 8.29(1H, d, J=6.6Hz), 8.41(1H, d, J=8.3Hz)______________________________________
TABLE 70__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________46 ##STR490##47 ##STR491##48 ##STR492##49 ##STR493##50 ##STR494##__________________________________________________________________________
TABLE 71______________________________________ .sup.1 H-NMR .delta. ppm______________________________________46 (solvent:DMSO-d.sub.6) 0.92(3H, t, J=7.3Hz), 1.55(2H, tq, J=6.9Hz, J=7.7Hz), 2.52(3H, s), 2.67(2H, t, J=7.6Hz), 3.67(2H, s), 5.50(2H, s), 6.77(1H, d, J=9.2Hz), 7.11(1H, s), 7.76(1H, d, J=7.2Hz) 7.81(1H, d, J=8.9Hz), 8.11(1H, dd, J=7.6Hz, J=7.6Hz), 8.15(1H, d, J=7.6Hz)47 (solvent:CDCL.sub.3) 1.00(3H, t, J=7.4Hz), 1.64(2H, tq, J=7.6Hz, J=7.3Hz), 2.59(3H, s), 2.78(2H, t, J=7.6Hz), 3.91(2H, s), 5.40(2H, s), 6.55(1H, d, J=8.9Hz), 7.07(1H, d, J=6.6Hz), 7.63(1H, d, J=8.2Hz), 7.77(1H, d, J=6.9Hz), 7.85(1H, dd, J=7.9Hz, J=7.9Hz), 8.02(1H, dd, J=7.6Hz, J=7.9Hz), 8.27(H, d, J=6.9Hz), 8.39(1H, d, J=8.3Hz)48 (solvent:CDCL.sub.3) 1.03(3h, t, J=7.3Hz), 1.64(2H, tq, J=7.6Hz, J=7.8Hz), 2.59(3H, s), 2.74(2H, t, J=8.0Hz), 3.78(3H, s), 3.82(2H, s), 5.31(2H, s), 6.71(1H, d, J=8.9Hz), 6.83(1H, s), 7.53(1H, d, J=8.9Hz), 7.70(1H, d, J=7.6Hz), 7.97(1H, dd, J=7.6Hz, J=7.9Hz), 8.19(1H, d, J=7.6Hz)49 (solvent:CDCL.sub.3) 1.03(3H, t, J=7.3Hz), 1.65(2H, tq, J=7.6Hz, J=7.9Hz), 2.63(3H, s), 2.76(2H, t, J=7.6Hz), 3.79(3H, s), 3.90(2H, s), 5.37(2H, s), 6.81(1H, d, J=8.6Hz), 7.06(1H, d, J=7.6Hz), 7.59(1H, d, J=8.9Hz), 7.75(1H, d, J=6.9Hz), 7.83(1H, dd, J=7.9Hz, J=7.9Hz), 8.01(1H, dd, J=7.9Hz, J=7.9Hz), 8.28(1H, d, J=6.9Hz)50 (solvent:DMSO-d.sub.6) 1.20(3H, t, J=7.6Hz), 2.58(3H, s), 2.64(2H, q, J=7.6Hz), 3.66(2H, s), 5.38(2H, s), 6.57(1H, s), 7.06(1H, s), 7.66(1H, d, J=8.6Hz), 7.69(1H, s), 8.48(1H, dd, J=2.0Hz, J=8.6Hz), 9.22(1H, d, J=2.0Hz), 12.54(1H, s)______________________________________
TABLE 72__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________51 ##STR495##52 ##STR496##53 ##STR497##54 ##STR498##55 ##STR499##__________________________________________________________________________
TABLE 73______________________________________ .sup.1 H-NMR .delta. ppm______________________________________51 (solvent: DMSO-d.sub.6) 1.19(3H, t, J=7.6Hz), 2.58(3H, s), 2.64(2H, q, J=7.6Hz), 4.64(2H, s), 5.45(2H, s), 6.62(1H, s), 6.93(2H, d, J=8.2Hz), 7.65-7.85(4H, m), 8.05-8.20(2H, m), 10.35(1H, s), 12.55(1H, s)52 (solvent:DMSO-d.sub.6) 1.20(3H, t, J=7.6Hz), 2.58(3H, s), 2.64(2H, q, J=7.6Hz), 4.66(2H, s), 5.46(2H, s), 6.62(1H, s), 6.65-6.75(1H, m), 7.20-7.80(5H, m), 8.05-8.20(2H, m), 10.41(1H, s) 12.56(1H, s),53 (solvent:DMSO-d.sub.6) 1.21(3H, t, J=7.3Hz), 2.58(3H, s), 2.65(2H, q, J=7.3Hz), 3.60(2H, s), 3.79(2H, d, J=5.6Hz), 5.46(2H, s) 6.63(1H, s), 7.09(1H, s), 7.70(1H, s), 7.75- 7.85(1H, m), 8.1-8.4(3H, m), 12.04(1H, bs), 12.56(1H, s)54 (solvent:CDCL.sub.3) 1.31(3H, t, J=7.6Hz), 1.52(2H, d, J=6.9Hz), 2.57(3H, s), 2.74(2H, q, J=7.6Hz), 3.71(2H, s), 4.60(1H, dq, J=7.6Hz, J=7.9Hz), 5.49(2H, s), 6.84(1H, s), 7.01(1H, d, J=7.3Hz), 7.51(1H, s), 7.63(1H, d, J=7.6Hz), 7.75(1H, dd, J=7.6Hz, J=8.2Hz), 7.93(1H, dd, J=7.6Hz, J=7.6Hz), 8.22(1H, d, J=7.9Hz), 8.33(1H, d, J=8.3Hz)55 (solvent:CDCL.sub.3) 1.27(3H, t, J=7.6Hz), 1.43(2H, d, J=7.3Hz), 2.59(3H, s), 2.71(2H, q, J=7.3Hz), 3.72(3H, s), 3.74(2H, s), 4.61(2H, dq, J=6.9Hz, J=7.2Hz), 5.39(2H, s), 6.49(1H, s), 7.06(1H, d, J=7.6Hz), 7.51(1H, s), 7.72(1H, d, J=7.6Hz), 7.76(1H, dd, J=7.2Hz, J=8.4Hz), 8.00(1H, dd, J=7.6Hz, J=7.9Hz), 8.27(1H, d, J=7.9Hz), 8.34(1H, d, J=8.6Hz)______________________________________
TABLE 74__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________56 ##STR500##57 ##STR501##58 ##STR502##59 ##STR503##60 ##STR504##__________________________________________________________________________
TABLE 75______________________________________ .sup.1 H-NMR .delta. ppm______________________________________56 (solvent:CDCL.sub.3) 1.28(3H, t, J=7.4Hz), 2.59(3H, s), 2.54(2H, t, J=6.1Hz), 2.70(2H, t, J=7.4Hz), 3.55(3H, s), 3.56(2H, dd, J=5.9Hz, J=6.3Hz), 3.69(2H, s), 5.39(2H, s), 6.50(1H, s), 7.06(1H, d, J=7.6Hz), 7.51(1H, s), 7.73(1H, dd, J=7.9Hz, J=1.0Hz), 7.75(1H, dd, J=7.6Hz, J=7.9Hz), 7.99(1H, dd, J=7.6Hz, J=7.9Hz), 8.30(1H, d, J=7.9Hz, J=1.0Hz), 8.32(1H, d, J=8.3Hz),57 (solvent:CDCL.sub.3) 1.28(3H, t, J=7.6Hz), 2.60(3H, s), 2.72(2H, q, J=7.5Hz), 3.76(2H, s), 5.40(2H, s), 6.55(1H, s), 7.13(1H, d, J=7.3Hz), 7.54(1H, s), 7.76(1H, dd, J=7.3Hz, J=7.6Hz), 7.81(1H, d, J=7.6Hz), 8.02(1H, dd, J=7.9Hz, J=7.9Hz), 8.25(1H, d, J=7.3Hz), 8.31(1H, d, J=8.2Hz)58 (solvent:CDCL.sub.3) 1.31(3H, t, J=7.6Hz), 1.52(2H, d, J=6.9Hz), 2.57(3H, s), 2.74(2H, q, J=7.6Hz), 3.71(2H, s), 4.60(1H, dq, J=7.6Hz, J=7.9Hz), 5.49(2H, s), 6.84(1H, s), 7.01(1H, d, J=7.3Hz), 7.51(1H, s), 7.63(1H, d, J=7.6Hz), 7.75(1H, dd, J=7.6Hz, J=8.2Hz), 7.93(1H, dd, J=7.6Hz, J=7.6Hz), 8.22(1H, d, J=7.9Hz), 8.33(1H, d, J=8.3Hz)59 (solvent:CDCL.sub.3) 1.28(3H, t, J=7.6Hz), 2.58(3H, s), 2.60(2H, q, J=5.9Hz), 2.71(2H, q, J=7.9Hz), 3.70(2H, s), 3.60(2H, q, J=5.7Hz), 5.44(1H, s), 6.74(1H, s), 7.03(1H, d, J=7.6Hz) 7.50(1H, s), 7.73(1H, d, J=7.3Hz), 7.74(1H, dd, J=8.5Hz, J=7.3Hz), 8.00(1H, dd, J=7.9Hz, J=7.6Hz), 8.25(1H, d, J=7.6Hz), 8.31(1H, d, J=8.2Hz)60 (solvent:CDCL.sub.3) 1.29(3H, t, J=7.6Hz), 2.60(3H, s), 2.73(2H, q, J=7.5Hz), 2.85(1H, dd, J=17.2Hz, J=5.3Hz), 3.00(1H, dd, J=14.2Hz, J=4.6Hz), 3.76(2H, s), 4.78(1H, t, J=5.0Hz), 5.41(2H, s), 6.55(1H, s), 7.13(1H, d, J=7.6Hz), 7.55(1H, s), 7.74(1H, d, J=7.8Hz), 7.79(1H, dd, J=7.6Hz, J=8.2Hz), 8.02(1H, dd, J=7.6Hz, J=7.9Hz), 8.23(1H, d, J=6.9Hz), 8.30(1H, d, J=8.6Hz)______________________________________
TABLE 76__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________61 ##STR505##62 ##STR506##63 ##STR507##64 ##STR508##65 ##STR509##__________________________________________________________________________
TABLE 77______________________________________ .sup.1 H-NMR .delta. ppm______________________________________61 (solvent:DMSO-d.sub.6) 1.19(3H, t, J=7.6Hz), 2.59(3H, s), 2.64(2H, q, J=7.6Hz), 3.67(2H, s), 5.49(2H, s), 6.69(1H, s), 7.12(1H, s), 7.71(1H, s), 9.04(1H, s), 9.27(1H, s), 10.06(1H, s), 12.58(1H, br)62 (solvent:CDCL.sub.3) 1.26(3H, t, J=7.6Hz), 1.30(3H, t, J=7.3Hz), 2.60 (3H, s), 2.69(2H, q, J=7.6Hz), 3.76(2H, d, J=0.7Hz), 4.22(2H, q, J=7.3Hz), 5.33(2H, s), 6.47(1H, s), 6.94(1H, s), 7.53(1H, s), 9.08 (1H, s), 9.48(1H, s), 10.90(1H, br), 12.70(1H, s)63 (solvent:DMSO-d.sub.6) 1.19(3H, t, J=7.6Hz), 2.59(3H, s), 2.66(2H, q, J=7.6Hz), 2.89(1H, dd, J=8.3Hz, 15.0Hz), 3.00(1H, dd, J=5.3Hz, 15.0Hz), 3.58(2H, s), 4.4-4.5(1H, m), 5.49(2H, s), 6.68(1H, s), 6.94(1H, s), 7.00(1H, s), 7.71(1H, s), 7.87(1H, s), 8.33(1H, d, J=7.6Hz), 9.05(1H, s), 9.27(1H, s), 12.60(1H, br)64 (solvent:CDCl.sub.3) 1.20(3H, t, J=7.3Hz), 2.60(3H, s), 2.70(2H, q, J=7.3Hz), 3.1-3.2(2H, m), 3.72(3H, s), 3.75(2H, s), 4.8-4.9(1H, m), 5.36(2H, s), 6.48(1H, s), 6.79(1H, s), 6.91(1H, s), 7.53(1H, s), 7.56(1H, s), 9.10(1H, s), 9.48(1H, s), 12.78(1H, br)65 (solvent:DMSO-d.sub.6) 1.19(3H, t, J=7.6Hz), 2.59(3H, s), 2.6-2.7(4H, m), 3.61(2H, s), 4.5-4.6(1H, m), 5.49(2H, s), 6.69(1H, s), 7.08(1H, s), 8.35(1H, d, J=7.6Hz), 9.05(1H, s), 9.27(1H, s), 12.60(1H, s),______________________________________
TABLE 78__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________66 ##STR510##67 ##STR511##68 ##STR512##69 ##STR513##70 ##STR514##__________________________________________________________________________
TABLE 79______________________________________ .sup.1 H-NMR .delta. ppm______________________________________66 (solvent:CDCl.sub.3) 1.16(3H, t, J=7.6Hz), 1.25(3H, t, J=7.6Hz), 1.26(3H, t, J=7.6Hz), 2.59(3H, s), 2.69(2H, q, J=7.6Hz), 2.8-3.1(2H, m), 3.71(2H, s), 4.11(2H, q, J=7.6Hz), 4.21(2H, q, J=7.6Hz), 4.8-4.9(1H, m), 5.37(2H, s), 6.47(1H, s), 6.91(1H, s), 7.52(1H, s), 8.03(1H, s), 9.08(1H, s), 9.49(1H, s), 12.68(1H, s),67 (solvent:CDCl.sub.3) 1.27(3H, t, J=7.6Hz), 2.59(3H, t), 2.70(2H, J=7.6Hz), 3.76(2H, s), 3.78(2H, d, J=0.7Hz), 5.28(2H, s), 6.43(1H, s), 7.51(1H, s), 6.90(1H, s), 7.72(1H, dd, J=7.9, 1.0Hz), 8.00(1H, dd, J=7.9, 7.6Hz), 8.25(1H, d, J=7.9Hz)68 (solvent:CDCl.sub.3) 1.28(3H, t, J=7.4Hz), 2.58(3H, s), 2.72(2H, q, J=7.5Hz), 3.77(2H, s), 4.05(2H, d, J=5.0Hz), 5.46(2H, s), 6.89(1H, s), 7.03(1H, d, J=6.6Hz), 7.5(1H, s), 7.72(1H, d, J=7.9Hz), 7.76(1H, dd, J=7.6, 7.9Hz), 7.99(1H, dd, J=7.6, 7.9Hz), 8.24(1H, d, J=7.6Hz), 8.30(1H, d, J=8.3Hz)69 (solvent:CDCl.sub.3) 1.27(3H, t, J=7.6Hz), 2.59(3H, s), 2.70(2H, q, J=7.3Hz), 3.72(2H, s), 3.8-4.0(2H, m), 4.58(3H, t, J=3.8Hz), 5.33 (2H, s), 6.48(1H, s), 6.94(1H, s), 7.52(1H, s), 7.76(1H, d, J=7.6Hz), 8.03(1H, dd, J=7.9, 7.9Hz), 8.25(1H, d, J=7.9Hz)70 (solvent:CDCl.sub.3) 1.27(3H, t, J=7.4Hz), 2.60(3H, s), 2.71(2H, q, J=7.5Hz), 3.37(2H, s), 3.73(3H, s), 3.87(1H, dd, J=11.5, 3.3Hz), 3.97(1H, dd, 11.5, 3.3Hz), 4.6-4.7(1H, m), 5.34(2H, s), 6.48(1H, s), 6.96(1H, s), 7.54(1H, s), 7.77(1H, d, J=7.6Hz), 8.04(1H, dd, J=7.9, 7.9Hz), 8.25(1H, d, J=7.6Hz)______________________________________
TABLE 80__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________71 ##STR515##72 ##STR516##73 ##STR517##74 ##STR518##75 ##STR519##__________________________________________________________________________
TABLE 81______________________________________ .sup.1 H-NMR .delta. ppm______________________________________71 (solvent:CDCl.sub.3) 1.27(3H, t, J=7.6Hz), 1.5-2.2(4H, m), 2.59(3H, s), 2.70(2H, q, J=7.6Hz), 3.5-3.7(2H, m), 3.85(2H, J=2.3Hz), 4.6-4.7(1H, m), 5.32(2H, s), 6.49(1H, s), 6.92(1H, s), 7.51(1H, s), 7.73(1H, d, J=7.9Hz), 7.99(1H, dd, J=7.9, 7.9Hz), 8.23(1H, d, J=7.9Hz)72 (solvent:CDCl.sub.3) 1.26(3H, t, J=7.6Hz), 1.9-2.3(4H, m), 2.59(3H, s), 2.70(2H, q, J=7.5Hz), 3.6-3.8(2H, m), 3.82(2H, s), 4.12(2H, q, J=7.2Hz), 4.63(1H, dd, J=8.3, 3.6Hz), 5.18(2H, d, J=7.9Hz), 5.27(2H, s), 6.44(1H, s), 6.94(1H, s), 7.35(5H, m), 7.51(1H, s), 7.72(1H, d, J=6.9Hz), 8.00(1H, dd, J=7.9, 7.9Hz), 8.25(1H, d, J=7.9Hz)73 (solvent:CDCl.sub.3) 1.27(3H, t, J=7.6Hz), 2.60(3H, s), 2.71(2H, q, J=7.3Hz), 2.8-3.1(2H, m), 3.37(2H, d, J=5.0Hz), 3.71(2H, s), 4.80(1H, t, J=4.8Hz), 5.35(2H, s), 6.49(1H, s), 6.93(1H, s), 7.54(1H, s), 7.76(1H, d, J=7.9Hz), 8.03(1H, dd, J=7.9, 7.9Hz), 8.23(1H, d, J=7.9Hz)74 (solvent:CDCl.sub.3) 1.19(3H, t, J=7.1Hz), 1.24(3H, t, J=7.4Hz), 1.27(3H, t, J=7.8Hz), 2.59(3H, s), 2.70(2H, q, J=7.2Hz), 2.85(1H, dd, J=17.2, 4.6Hz), 3.02(1H, dd, J=16.8, 4.6Hz), 3.72(2H, s), 4.10(2H, q, J=7.2Hz), 4.20(2H, q, J=7.1Hz), 4.85(1H, td, J=4.9, 7.6Hz), 5.31(2H, s), 6.44(1H, s), 6.89(1H, s), 7.51(1H, s), 7.74(1H, d, J=7.6Hz), 8.01(1H, dd, J=7.6, 7.9Hz), 8.26(1H, d, J=7.6Hz)75 (solvent:CDCl.sub.3) 1.27(3H, t, J=7.5Hz), 2.59(3H, s), 2.69(2H, q, J=7.3Hz), 3.26(2H, d, J=5.0Hz), 3.70(2H, s), 4.70(1H, t, J=5.0Hz), 5.33(2H, s), 6.48(1H, s), 6.95(1H, s), 7.05(1H, s), 7.50(1H, s), 7.76(1H, d, J=8.0Hz), 8.00(1H, dd, J=8.0, 8.0Hz), 8.22(1H, d, J=8.0Hz)______________________________________
TABLE 82__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________76 ##STR520##77 ##STR521##78 ##STR522##79 ##STR523##80 ##STR524##__________________________________________________________________________
TABLE 83______________________________________ .sup.1 H-NMR .delta. ppm______________________________________76 (solvent:CDCl.sub.3) 1.26(3H, t, J=7.5Hz), 2.59(3H, s), 2.69(2H, q, J=7.5Hz), 3.15(2H, t, J=4.2Hz), 3.71(3H, s), 3.73(2H, s), 4.84(1H, dt, J=7.3, 4.2Hz), 5.31(2H, s), 6.45(1H, s), 6.78(1H, s), 6.88(1H, s), 7.50(1H, s), 7.59(1H, s), 7.72(1H, d, J=7.6Hz), 8.01(1H, dd, J=7.9, 7.9Hz), 8.26(1H, d, J=7.6Hz),77 (solvent:CDCl.sub.3) 1.27(3H, t, J=7.5Hz), 1.9-2.5(4H, m), 2.0-2.5(4H, m), 2.60(3H, s), 2.71(2H, q, J=7.5Hz), 3.70(2H, s), 4.56(1H, t, J=4.0Hz), 5.35(2H, s), 6.49(1H, s), 6.94(1H, s), 7.36(1H, s), 7.77(1H, d, J=7.9Hz), 8.04(1H, dd, J=7.6, 7.9Hz), 8.24(1H, d, J=7.6Hz)78 (solvent:CDCl.sub.3) 1.21(3H, t, J=7.1Hz), 1.26(3H, t, J=7.4Hz), 1.29(3H, t, J=7.6Hz), 1.9-2.4(4H, m), 2.59(3H, s), 2.70(2H, q, J=7.4Hz), 3.70(2H, s), 4.09(2H, q, J=7.2Hz), 4.19(2H, q, J=6.9Hz), 4.63(1H, td, J=3.7, 7.6Hz), 5.33(2H, s), 6.47(1H, s), 6.88(1H, s), 7.51(1H, s), 7.75(1H, d, J=6.9Hz), 8.02(1H, dd, J=6.9, 7.6Hz), 8.26(1H, d, J=6.9Hz)79 (solvent:CDCl.sub.3) 1.21(3H, t, J=7.6Hz), 2.51(3H, s), 2.62(2H, q, J=7.6Hz), 3.20(2H, br), 4.71(1H, t, J=5.3Hz), 5.23(2H, s), 6.43(1H, s), 7.41(1H, s), 7.05(1H, s), 7.05(1H, d, J=7.3Hz), 7.31(1H, s), 7.61(1H, dd, J=7.9Hz), 7.67(1H, dd, J=7.9, 7.9Hz), 7.90(1H, dd, J=7.6, 7.6Hz), 8.12(1H, d, J=7.3Hz), 8.19(1H, d, J=8.3Hz),80 (solvent:CDCl.sub.3) 1.27(3H, t, J=7.4Hz), 2.59(3H, s), 2.70(2H, q, J=7.4Hz), 3.17(2H, J=5.0Hz), 3.67(3H, s), 3.77(2H, s), 4.82(1H, dt, J=6.9, 5.0Hz), 5.22(2H, s), 6.35(1H, s), 6.71(1H, s), 7.07(1H, d, J=7.3Hz), 7.45(1H, s), 7.51(1H, s), 7.67(1H, d, J=7.3Hz), 7.76(1H, dd, J=7.9, 7.9Hz), 7.98(1H, dd, J=7.9, 7.9Hz), 8.26(1H, d, J=6.9Hz), 8.32(1H, d, J=7.9Hz)______________________________________
TABLE 84__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________81 ##STR525##82 ##STR526##83 ##STR527##84 ##STR528##85 ##STR529##__________________________________________________________________________
TABLE 85______________________________________ .sup.1 H-NMR .delta. ppm______________________________________81 (solvent:CDCl.sub.3) 1.28(3H, t, J=7.4Hz), 1.9-2.5(4H, m), 2.60(3H, s), 2.72(2H, q, J=7.4Hz), 3.84(2H, s), 4.5- 4.6(1H, m), 5.42(2H, s), 6.56(2H, s), 7.26(1H, d, J=7.9Hz), 7.54(1H, s), 7.76(1H, d, J=8.3Hz, 7.94(1H, dd, J=7.9, 7.9Hz), 8.03(1H, dd, J=7.9, 7.6Hz), 8.24(1H, d, J=7.9Hz), 8.39(1H, d, J=8.6Hz)82 (solvent:CDCl.sub.3) 1.16(3H, t, J=7.3Hz), 1.20(3H, t, J=7.1Hz), 1.27(3H, t, J=7.4Hz), 2.59(3H, s), 2.71(2H, q, J=7.4Hz), 2.0-2.4(4H, m), 3.74(2H, s), 4.03(2H, q, J=7.1Hz), 4.1-4.3(2H, m), 4.65(1H, td, J=7.6, 5.3Hz), 5.39(2H, s), 6.49(1H, s), 7.06(1H, d, J=6.6Hz), 7.51(1H, s), 7.71(1H, d, J=7.3Hz), 7.73(1H, dd, J=7.9, 7.9Hz), 7.99(1H, dd, J=7.6, 7.9Hz), 8.27(1H, d, J=7.9Hz), 8.34(1H, d, J=7.9Hz)83 (solvent:CDCl.sub.3) 1.27(3H, t, J=7.4Hz), 2.0-2.1(4H, m), 2.58(3H, s), 2.71(2H, q, J=7.4Hz), 3.67(2H, m), 3.94(2H, d, J=4.3Hz), 4.75(1H, d, J=5.9Hz), 5.39(2H, s), 6.56(2H, s), 7.10(1H, d, J=7.6Hz), 7.50(1H, s), 7.71(1H, d, J=7.9Hz), 7.78(1H, dd, J=7.9, 7.9Hz), 7.98(1H, dd, J=7.9, 7.6Hz), 8.24(1H, d, J=7.6Hz), 8.37(1H, d, J=8.3Hz)84 (solvent:CDCl.sub.3) 1.26(3H, t, J=7.6Hz), 1.9-2.3(4H, m), 2.58(3H, s), 2.70(2H, q, J=7.5Hz), 3.6-3.8(2H, m), 3.88(2H, s), 4.12(2H, q, J=7.2Hz), 4.63(1H, dd, J=8.3, 3.6Hz), 5.17(2H, d, J=7.9Hz), 5.31(2H, s), 6.47(1H, s), 7.15(1H, d, J=6.6Hz), 7.34(5H, m), 7.50(1H, s), 7.67(1H, d, J=7.6Hz), 7.68(1H, dd, J=7.9, 7.6Hz), 7.97(1H, dd, J=7.9, 7.6Hz), 8.26(1H, d, J=6.9Hz), 8.30(1H, d, J=8.3Hz)85 (solvent:CDCl.sub.3) 1.28(3H, t, J=7.4Hz), 2.60(3H, s), 2.72(2H, q, J=7.4Hz), 3.79(2H, s), 3.8- 4.1(2H, m), 4.59(1H, t, J=3.5Hz), 5.39(2H, s), 6.52(1H, s), 7.54(1H, s), 7.74(1H, d, J=7.9Hz), 7.80(1H, dd, J=7.6, 8.3Hz), 8.02(1H, dd, J=7.9, 7.6Hz), 8.24(1H, d, J=7.9Hz), 8.31(1H, d, J=8.2Hz), 7.15(1H, d, J=7.3Hz)______________________________________
TABLE 86__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________86 ##STR530##87 ##STR531##88 ##STR532##89 ##STR533##90 ##STR534##__________________________________________________________________________
TABLE 87______________________________________ .sup.1 H-NMR .delta. ppm______________________________________86 (solvent:CDCl.sub.3) 1.27(3H, t, J=7.4Hz), 2.58(3H, s), 2.69(2H, q, J=7.4Hz), 3.74(3H, s), 3.79(2H, s), 4.00(2H, d, J=3.3Hz), 4.71(1H, dt, J=7.3, 3.6Hz), 5.38(2H, s), 6.50(1H, s), 7.05(1H, d, J=6.6Hz), 7.49(1H, s), 7.70(1H, d, J=7.9Hz), 7.75(1H, dd, J=7.6, 8.2Hz), 7.98(1H, dd, J=7.9, 6.7Hz), 8.25(1H, d, J=6.6Hz), 8.27(1H, d, J=8.2Hz)87 (solvent:DMSO-d.sub.6) 1.19(3H, t, J=7.6Hz), 2.60(3H, s), 2.64(2H, q, J=7.6Hz), 3.53(2H, s), 5.49(2H, s), 6.55(1H, s), 6.89(1H, s), 7.64(1H, s), 8.04(1H, d, J=5.0Hz), 9.05(1H, s)(DMSO-d.sub.6)88 (solvent:CDCl.sub.3) 1.27(3H, t, J=7.6Hz), 1.29(3H, t, J=7.3Hz), 2.58(3H, s), 2.71(2H, q, J=7.6Hz), 3.76(2H, s), 4.21(2H, q, J=7.3Hz), 5.43(2H, s), 6.41(1H, s), 6.94(1H, s), 7.51(1H, s), 8.13(1H, d, J=5.0Hz), 9.09(1H, d, J=5.0Hz), 10.93(br), 12.64(1H, s)89 (sovlent:DMSO-d.sub.6) 1.22(3H, t, J=7.6Hz), 2.59(3H, s), 2.67(2H, q, J=7.6Hz), 3.73(2H, s), 5.56(2H, s), 6.71(1H, s), 7.20(1H, d, J=7.6Hz), 7.71(1H, s), 7.89(1H, dd, J=7.6Hz, 7.9Hz), 8.16(1H, d, J=7.9Hz), 9.08(1H, s), 9.32(1H, s), 10.22(1H, s), 12.58(1H, s)90 (solvent:CDCl.sub.3) 1.27(3H, i, J=7.6Hz), 1.28(3H, t, J=7.3Hz), 2.60(3H, s), 2.70(2H, q, J=7.6Hz), 3.80(2H, s), 4.21(2H, q, J=7.3Hz), 5.38(2H, s), 6.50(1H, s), 7.12(1H, dd, J=0.7Hz, 7.6Hz), 7.52(1H, s), 7.78(1H, t, J=7.9Hz), 8.34(1H, d, J=8.3Hz), 9.04(1H, s), 10.06(1H, s), 12.68(1H,______________________________________ s)
TABLE 88__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________91 ##STR535##92 ##STR536##93 ##STR537##94 ##STR538##95 ##STR539##__________________________________________________________________________
TABLE 89______________________________________ .sup.1 H-NMR .delta. ppm______________________________________91 (solvent:CDCl.sub.3) 1.22(3H, t, J=7.6Hz), 2.58(3H, s), 2.65(2H, q, J=7.6Hz), 3.72(2H, s), 5.20(2H, s), 6.47(1H, s), 6.87(1H, s), 7.50(1H, s), 7.58(1H, dd, J=7.6, 7.6Hz), 7.69(1H, d, J=7.6Hz), 7.98(1H, d, J=7.6Hz), 8.09(1H, s)92 (solvent:CDCl.sub.3) 1.22(3H, t, J=7.4Hz), 1.28(3H, t, J=7.1Hz), 2.58(3H, s), 2.64(2H, q, J=7.4Hz), 3.69(2H, s), 4.19(2H, q, J=7.1Hz), 5.18(2H, s), 6.45(1H, s), 6.86(1H, s), 7.47(1H, s), 7.57(1H, dd, J=7.6, 7.6Hz), 7.68(1H, d, J=7.6Hz), 7.88(1H, d, J=7.6Hz), 8.02(1H, s)93 (solvent:CDCl.sub.3) 1.28(3H, t, J=7.6Hz), 1.47(3H, d, J=7.3Hz), 2.60(3H, s), 2.72(2H, q, J=7.6Hz), 3.89(2H, s), 4.50(1H, dt, J=7.2, 7.3Hz), 5.45(2H, s), 6.57(1H, s), 7.34(1H, d, J=7.6Hz), 7.53(1H, s), 7.78(1H, d, J=7.9Hz), 8.02(1H, dd, J=7.6, 7.9Hz), 8.03(1H, dd, J=7.6, 7.6Hz), 8.23(1H, d, J=7.6Hz), 8.45(1H, d, J=8.2Hz),94 (solvent:CDCl.sub.3) 1.27(3H, t, J=7.6Hz), 1.43(3H, d, J=7.3Hz), 2.59(3H, s), 2.71(2H, q, J=7.6Hz), 3.72(3H, s), 3.74(2H, s), 4.61(1H, qd, J=7.1Hz), 5.39(2H, s), 6.49(1H, s), 7.06(1H, d, J=7.3Hz), 7.51(1H, s), 7.72(1H, d, J=7.3Hz), 7.76(1H, dd, J=7.9, 7.6Hz), 8.00(1H, dd, J=7.9, 7.6Hz), 8.27(1H, d, J=8.6Hz), 8.34(1H, d, J=8.3Hz)95 (solvent:CDCl.sub.3 /MeoD(4/1)) 1.28(3H, t, J=7.6Hz), 2.60(3H, s), 2.72(2H, q, J=7.6Hz), 3.77(2H, s), 3.97(2H, s), 3.99(2H, s), 5.38(2H, s), 6.53(1H, s), 7.14(1H, d, J=7.6Hz), 7.37(1H, s), 7.75(1H, d, J=7.9Hz), 7.79(1H, dd, J=7.6, 8.2Hz), 8.02(1H, dd, J=7.6, 7.9Hz), 8.25(1H, d, J=7.9Hz), 8.30(1H, d, J=8.2Hz)______________________________________
TABLE 90__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________96 ##STR540##97 ##STR541##98 ##STR542##99 ##STR543##100 ##STR544##__________________________________________________________________________
TABLE 91______________________________________ .sup.1 H-NMR .delta. ppm______________________________________96 (solvent:CDCl.sub.3) 1.21(3H, t, J=7.1Hz), 1.27(3H, t, J=7.4Hz), 2.58(3H, s), 2.71(2H, q, J=7.4Hz), 3.78(2H, s), 4.0-4.1(4H, m), 4.12(2H, q, J=7.1Hz), 5.40(2H, s), 6.52(1H, s), 7.07(1H, d, J=7.3Hz), 7.50((1H, s), 7.72(1H, d, J=7.9Hz), 7.76(1H, t, J=8.3, 7.6Hz), 7.99(1H, dd, J=7.9, 7.9Hz), 8.27(1H, d, J=8.6Hz), 8.30(1H, d, J=8.9Hz)97 (solvent:DMSO-d.sub.6) 1.30(3H, t, J=7.6Hz), 2.59(3H, s), 2.72(2H, q, J=7.6Hz), 3.49(1H, s), 4.13(2H, s), 5.40(2H, s), 6.48(1H, s), 7.17(1H, dd, J=1.8Hz, 7.9Hz), 7.51(1H, s), 7.61(1H, dd, J=7.9Hz, 8.3Hz), 7.76(1H, d, J=7.9Hz), 8.02(1H, dd, J=7.9Hz, 7.9Hz), 8.26(1H, d, J=8.6Hz), 8.75(1H, dd, J=1.8Hz, 8.3Hz), 12.18(1H, br), 12.63(1H, s),98 (solvent:CDCl.sub.3) 1.27(3H, t, J=7.6Hz), 1.31(1H, t, J=7.1Hz), 2.58(3H, s), 2.70(2H, q, J=7.6Hz), 3.99(2H, s), 4.26(2H, q, J=7.1Hz), 5.35(2H, s), 6.46(1H, s), 7.11(1H, dd, J=1.7Hz, 7.9Hz), 7.36(1H, dd, J=7.9Hz, 7.9Hz), 7.49(1H, s), 7.72(1H, dd, J=1.0Hz, 7.9Hz), 7.98(1H, dd, J=7.9Hz, 7.9Hz), 8.23(1H, dd, J= 1.0Hz, 7.9Hz), 8.63(1H, dd, J=2.0Hz), 8.6Hz), 12.29(1H, br), 12.62(1H, s)99 (solvent:CDCl.sub.3) 1.29(3H, t, J=7.4Hz), 2.57(3H, s), 2.72(2H, t, J=7.4Hz), 2.96(1H, dd, J=17.0, 4.5Hz), 3.09(1H, dd, J=17.0, 4.5Hz), 3.77(2H, s), 4.85(1H, br), 5.49(2H, d, J=3.3Hz), 6.72(1H, s), 7.02(1H, d, J=8.3Hz), 7.49(1H, s), 7.65(1H, d, J=7.9Hz), 7.75(1H, dd, J=7.6, 8.3Hz), 7.94(1H, dd, J=7.6, 8.3Hz), 7.94(1H, dd, J=7.9, 7.6Hz), 8.19(1H, d, J=7.6Hz), 8.32(1H, d, J=8.3Hz)100 (solvent:CDCl.sub.3) 1.10(3H, t, J=7.0Hz), 1.17(3H, t, J=7.1Hz), 1.28(3H, t, J=7.4Hz), 2.59(3H, s), 2.71(2H, q, J=7.4Hz), 2.85(1H, dd, J=17.0, 4.6Hz), 3.02(1H, dd, J=17.0, 4.6Hz), 3.75(2H, s), 4.00(2H, q, J=7.1Hz), 4.16(2H, q, J=7.0Hz), 4.85(1H, dt, J=7.6, 4.6Hz), 5.39(2H, s), 6.49(1H, s), 7.05(1H, d, J=7.3Hs), 7.51(1H, s), 7.72(1H, d, J=7.6Hz), 7.73(1H, dd, J=7.3, 7.6Hz), 7.99(1H, dd, J=7.6, 7.9Hz), 8.27(1H, d, J=7.3Hz), 8.34(1H, d, J=8.3Hz)______________________________________
TABLE 92__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________101 ##STR545##102 ##STR546##103 ##STR547##104 ##STR548##105 ##STR549##__________________________________________________________________________
TABLE 93______________________________________ .sup.1 H-NMR .delta. ppm______________________________________101 (solvent:DMSO-d.sub.6) 1.17(3H, t, J=7.6Hz), 2.56(3H, s), 2.59(1H, m), 2.69(1H, m), 3.59(2H, s), 3.6- 4.3(2H, br), 4.56(1H, m), 5.29(2H, s), 6.60(1H, s), 6.96(1H, s), 6.96(1H, s), 7.56(1H, t, J=7.9Hz), 7.64(1H, s), 7.68(1H, d, J=7.9Hz), 8.07(1H, d, J=7.9Hz), 8.19(1H, s), 8.23(1H, d, J=7.6Hz), 12.6(1H, s)102 (solvent:CDCl.sub.3 /DMSO-d.sub.6 (10/1)) 1.15-1.31(9H, m), 2.57(3H, s), 2.64(2H, q, J=7.3Hz), 2.84(1H, dd, J=17.2, 4.6Hz), 3.03(1H, dd, J=17.2, 4.3Hz), 3.67(2H, s), 4.15- 4.27(4H, m), 4.85(1H, ddd, J=7.9, 4.6, 4.3Hz), 5.19(1H, s), 6.46(1H, s), 6.78(1H, s), 7.48(1H, s), 7.57(1H, t, J=7.9Hz), 7.69(1H, d, J=7.9Hz), 7.94(1H, brd, J=8.3Hz), 7.97(1H, d, J=7.9Hz), 8.10(1H, s), 12.68(1H, s)103 (solvent:DMSOO-d.sub.6) 1.21(3H, t, J=7.3Hz), 2.58(H, s), 2.6-2.7(4H, m), 4.08(1H, s), 4.60(1H, m), 5.46(2H, s), 5.6-6.4(2H, br), 6.62(1H, s), 7.68(1H, s), 7.80(2H, d), 8.15(2H, m), 8.78(1H, d, J=7.9Hz), 12.55(1H, s)104 (solvent:CDCl.sub.3) 1.23-1.65(9H, m), 2.59(3H, s), 2.70(2H, q, J=7.3Hz), 2.85(1H, dd, J=17.2, 4.6Hz), 3.05(1H, dd, J=17.2, 4.6Hz), 4.10(2H, s), 4.15(2H, q, J=7.3Hz), 4.22(2H, q, J=7.3Hz), 4.87(1H, dt, J=7.9, 4.6Hz), 5.32(1H, s), 6.45(1H, s), 7.24(1H, brd), 7.52(1H, s), 7.75(1H, d, J=7.3Hz), 8.01(1H, t, J=7.9Hz), 8.26(1H, d, J=7.9Hz), 12.67(1H, s)105 (solvent:DMSO-d.sub.6) 0.96(6H, m), 1.30(3H, t, J=7.6Hz), 2.17(1H, m), 2.58(3H, s), 2.73(2H, q, J=7.6Hz), 3.75(2H, m), 4.67(1H, m), 5.42(2H, s), 6.83(1H, s), 7.02(1H, d, J=7.9Hz), 7.51(1H, s), 7.65(1H, d, J=7.9Hz), 7.75(1H, t, J=7.9Hz), 7.95(1H, t, J=7.9Hz), 8.22(1H, d, J=7.9Hz), 8.32(1H, d, J=7.9Hz), 8.91(1H, brd), 10.87(1H, s)______________________________________
TABLE 94__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________106 ##STR550##107 ##STR551##108 ##STR552##109 ##STR553##110 ##STR554##__________________________________________________________________________
TABLE 95______________________________________ .sup.1 H-NMR .delta. ppm______________________________________106 (solvent:CDCl.sub.3) 0.91(3H, m), 1.27(3H, t, J=7.3Hz), 2.18(1H, m), 2.59(3H, s), 2.71(2H, q, J=7.3Hz), 3.71(3H, s), 3.76(2H, s), 4.60(1H, s), 5.34(2H, s), 6.46(1H, s), 7.05(1H, d, J=7.6Hz), 7.51(1H, s), 7.73(1H, t, J= 7.6Hz), 7.78(1H, d, J=7.9Hz), 7.97(1H, br), 8.00(1H, t, J=7.9Hz), 8.27(1H, d, J=7.9Hz), 8.35(1H, d, J=7.9Hz), 10.54(1H, s), 12.62(1H, s)107 (solvent:DMSO-d.sub.6) 1.31(3H, t, J=7.6Hz), 2.01(3H, s), 2.15(1H, m), 2.35(1H, m), 2.55(2H, m), 2.58(3H, s), 2.74(2H, q, J=7.6Hz), 3.80(1H, d, J=15.8Hz), 3.68(1H, d, J=15.8Hz), 4.73(1H, m), 5.48(2H, s), 6.83(1H, s), 7.02(1H, d, J=7.6Hz), 7.51(1H, s), 7.63(1H, d, J=7.6Hz), 7.75(1H, t, J=7.6Hz), 7.94(1H, t, J=7.6Hz), 8.22(1H, d, J=7.6Hz), 8.33(1H, d, J=7.6Hz), 9.08(1H, brd), 10.87(1H, s)108 (solvent:CDCl.sub.3) 1.1-1.3(6H, m), 2.00(3H, s), 2.05-2.2(2H, m), 2.47(2H, m), 2.59(3H, s), 2.70(2H, q, J=7.3Hz), 3.74(2H, s), 4.16(2H, m), 4.71(1H, m), 5.40(2H, s), 6.50(1H, s), 7.06(1H, d, J=7.6Hz), 7.51(1H, s), 7.75(1H, t, J=7.6Hz), 7.77(1H, d, J=7.9Hz), 7.96(1H, br), 8.00(1H, t, J=7.6Hz), 8.27(1H, d, J=7.3Hz), 8.34(1H, d, J=8.3Hz), 10.53(1H, s), 12.63(1H, s)109 (solvent:DMSO-d.sub.6) 1.21(3H, t, J=7.3Hz), 2.51(3H, s), 2.63(4H, m), 3.89(2H, s), 4.59(1H, m), 5.42(2H, s), 6.63(1H, s), 7.29(1H, d, J=8.3Hz), 7.44(1H, t, J= 8.3Hz), 7.65(1H, s), 7.83(1H, d, J=7.3Hz), 8.18(1H, t, J=7.3Hz), 8.23(1H, brd), 8.47(1H, d, J=8.3Hz), 8.59(1H, d, J=7.3Hz), 12.16(1H, s), 12.51(1H, s), 12.6(2H, br)110 (solvent:CDCl.sub.3) 1.15(3H, t, J=7.3Hz), 1.17(3H, t, J=7.3Hz), 1.27(3H, t, J=7.3Hz), 2.59(3H, s), 2.71(1H, q, J=7.3Hz), 2.83(1H, dd, J=16.8Hz, 5.3Hz), 2.94(1H, dd, J=16.8Hz, 5.3Hz), 3.96(1H, d, J=13.5Hz), 4.07(1H, d, J=13.5Hz), 4.11(2H, q, J=7.3Hz), 4.12(2H, q, J=7.3Hz), 4.81(1H, dt, J=8.2Hz, 5.3Hz), 5.39(2H, s), 6.48(1H, s), 7.18(1H, dd, J=7.9Hz, 1.7Hz), 7.41(1H, t, J=7.9Hz), 7.50(1H, s), 7.76(1H, d, J=7.9Hz), 8.01(1H, t, J=7.9Hz), 8.25(1H, d, J=7.9Hz), 8.63(1H, dd, J=7.4Hz, 1.7Hz), 8.69(1H, d, J=8.2Hz), 12.32(1H, s), 12.61(1H, s)______________________________________
TABLE 96__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________111 ##STR555##112 ##STR556##113 ##STR557##114 ##STR558##115 ##STR559##__________________________________________________________________________
TABLE 97______________________________________.sup.1 H-NMR .delta. ppm______________________________________111 (solvent:DMSO-d.sub.6) 1.12(3H, d, J=6.6Hz), 1.22(3H, t, J= 7.6Hz), 2.30(1H, dd, J=15.2Hz, 7.3Hz), 2.46(1H, dd, J= 15.2Hz, 7.3Hz), 2.58(3H, s), 2.67(2H, q, J=7.6Hz), 3.56(2H, s), 4.10(1H, m), 5.47(2H, s), 6.64(2H, s), 7.13(1H, d, J= 7.6Hz), 7.69(1H, s), 7.80-7.86(2H, m), 8.10-8.30(4H, m), 10.35(1H, s), 12.17(1H, s), 12.56(1H, s)112 (solvent:CDCl.sub.3) 1.26(6H, m), 2.53(2H, d, J=5.3Hz), 2.59 (3H, s), 2.71(3H, s), 2.71(2H, m), 3.55(3H, s), 3.68(2H, s), 4.36(1H, m), 5.36(2H, s), 6.47(1H, s), 7.06(1H, d, J=7.6Hz), 7.42(1H, brd, J=7.9Hz), 7.51(1H, s), 7.70(1H, d, J=7.6Hz), 7.75(1H, t, J=7.6Hz), 7.99(1H, t, J=7.6Hz), 8.27(1H, d, J= 7.6Hz), 8.31(1H, d, J=7.6Hz), 10.48(1H, s), 12.65(1H, s)113 (solvent:DMSO-d.sub.6) 1.23(3H, t, J=7.3Hz), 2.14(1H, m), 2.6 (1H, m), 2.58(3H, s), 2.67(2H, q, J=7.3Hz), 3.45-3.70(2H, m), 3.83(1H, m), 4.22(1H, m), 5.02(0.4H, m), 4.57(0.6H, m), 5.48(2H, s), 6.65(1H, s), 7.14(1H, m), 7.69(1H, s), 7.65-7.90 (2H, m), 8.15-8.30(3H, m), 10.32(0.6H, s), 10.34(0.4H, s), 12.55(1H, s), 12.90(1H, br)114 (solvent:CDCl.sub.3) 1.27(3H, t, J=7.6Hz), 2.20-2.40(1H, m), 2.5-2.7(1H, m), 2.59(3H, s), 2.71(2H, q, J=7.6Hz), 3.64 (0.4H, s), 3.68(0.6H, s), 3.77(0.6H, s), 3.80(0.4H, s), 4.05-4.40 (2H, m), 4.79(0.6H, m), 4.95(0.4H, m), 5.34(2H, s), 6.48(1H, s), 7.13(0.4H, d, J=7.6Hz), 7.19(0.6H, d, J=7.6Hz), 7.51 (1H, s), 7.70(1H, d, J=7.6Hz), 7.75(1H, m), 7.98(1H, t, J= 7.6Hz), 8.27(1H, d, J=7.6Hz), 8.32(1H, d, J=7.6Hz), 10.34 (1H, s), 12.67(1H, s)115 (solvent:CDCl.sub.3) 1.28(3H, t, J=7.6Hz), 2.58(3H, s), 2.72(2H, q, J=7.6Hz), 2.91(2H, t, J=5.7Hz), 3.87(2H, s), 3.92(2H, t, J=5.7Hz), 5.46(2H, s), 6.60(1H, s), 6.88(1H, d, J=7.3Hz), 7.12(1H, d, J=6.6Hz), 7.50(1H, s), 7.62(1H, dd, J=7.6, 8.3Hz), 7.73(1H, d, J=7.9Hz), 7.78(1H, dd, J=7.6, 8.3Hz), 7.98(1H, dd, J=7.6, 7.9Hz), 8.06(1H, d, J=8.3Hz), 8.27(1H, d, J=7.9Hz), 8.40(1H, d, J=7.6Hz)______________________________________
TABLE 98__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________116 ##STR560##117 ##STR561##118 ##STR562##119 ##STR563##120 ##STR564##__________________________________________________________________________
TABLE 99______________________________________.sup.1 H-NMR .delta. ppm______________________________________116 (solvent:CDCl.sub.3 /MeODC(1/4))1.28(3H, t, J=7.6Hz), 2.60 (3H, s), 2.72(2H, q, J=7.6Hz), 2.88(2H, t, J=6.3Hz), 3.86 (2H, t, J=6.3Hz), 3.97(2H, s), 5.39(2H, s), 6.52(1H, s), 6.68 (1H, s), 7.19(1H, d, J=7.6Hz), 7.55(1H, s), 7.76(1H, d, J= 7.9Hz), 7.83(1H, dd, J=8.2, 7.6Hz), 8.05(1H, dd, J=7.6, J= 7.9Hz), 8.25(1H, d, J=7.6Hz), 8.33(1H, d, J=8.2Hz)117 (solvent:CDCl.sub.3) 1.0-1.3(5H, m), 2.59(3H, s), 2.71(2H, q, J=7.5Hz), 3.4-3.9(6H, m), 3.4-3.9(6H, m), 3.93(2H, s), 5.35(2H, s), 6.49(1H, s), 7.0-7.2(1H, m), 7.51(1H, s), 7.6-8.4(5H, m)118 (solvent:CDCl.sub.3) 1.27(3H, t, J=7.4Hz), 2.58(3H, s), 2.70(2H, q, J=7.4Hz), 3.6-4.0(8H, m), 4.00(2H, s), 5.35(2H, s), 6.51(1H, s), 7.11(1H, d, J=7.6Hz), 7.50(1H, s), 7.70(1H, d, J=7.6Hz), 7.76(1H, dd, J=7.6, 7.6Hz), 7.97(1H, dd, J=7.6, 7.9Hz), 8.24(1H, d, J=7.9Hz), 8.32(1H, d, J=7.6Hz)119 (solvent:CDCl.sub.3) 1.28(3H, t, J=7.4Hz), 2.60(3H, s), 2.71(2H, q, J=7.4Hz), 3.42(2H, t, J=6.6Hz), 3.68(2H, t, J=6.6Hz), 3.71(2H, s), 5.37(2H, s), 6.50(1H, s), 7.13(1H, d, J=7.6Hz), 7.53(1H, s), 7.74(1H, d, J=7.6Hz), 7.76(1H, dd, J=8.2, 7.6Hz), 8.02(1H, dd, J=7.6, 7.6Hz), 8.25(1H, d, J=7.6Hz), 8.27(1H, d, J=8.2Hz)120 (solvent:CDCl.sub.3) 1.27(3H, t, J=7.4Hz), 2.59(3H, s), 2.71(2H, q, J=7.4Hz), 2.93(2H, t, J=6.8Hz), 4.48(2H, t, J=6.8Hz), 5.32(2H, s), 6.31(1H, d, J=8.1Hz), 6.45(1H, d, J=8.1Hz), 7.03(1H, d, J=7.6Hz), 7.29(1H, d, J=8.1, 8.1Hz), 7.69(1H, d, J=7.6Hz) 7.71(1H, dd, J=7.6, 7.6Hz), 7.97(1H, dd, J= 7.6, 7.6Hz), 8.26(1H, d, J=7.6Hz), 8.33(1H, d, J=7.6Hz)______________________________________
TABLE 100__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________121 ##STR565##122 ##STR566##123 ##STR567##124 ##STR568##125 ##STR569##__________________________________________________________________________
TABLE 101______________________________________.sup.1 H-NMR .delta. ppm______________________________________121 (solvent:CDCl.sub.3) 1.28(3H, t, J=7.4Hz), 2.59(3H, s), 2.71(2H, q, J=7.4Hz), 2.96(2H, t, J=5.5Hz), 3.96(2H, t, J=5.5Hz), 5.33(2H, s), 6.45(1H, s), 6.73(1H, s), 7.51(1H, s), 7.72(1H, d, J=6.9Hz), 8.00(1H, dd, J=7.9, 7.6Hz), 8.25(1H, dd, J=7.6Hz)122 (solvent:DMSO-d.sub.6) 0.41(3H, t, J=7.6Hz), 1.30(3H, t, J= 7.6Hz), 1.7-1.9(2H, m), 2.57(3H, s), 3.74(2H, ABq, J= 15.4Hz, 5.5Hz), 4.66(1H, m), 5.46(2H, s), 6.83(1H, s), 7.02 (1H, d, J=7.6Hz), 7.51(1H, s), 7.63(1H, d, J=7.6Hz), 7.75 (1H, t, J=7.6Hz), 7.94(1H, t, J=7.6Hz), 8.22(1H, d, J= 7.6Hz), 8.32(1H, d, J=7.6Hz), 8.94(1H, m), 10.86(1H, s)123 (solvent:CDCl.sub.3) 0.88(3H, t, J=7.3Hz), 1.27(3H, t, J= 7.6Hz), 1.7-1.9(2H, m), 2.59(3H, s), 2.71(2H, q, J=7.6Hz), 3.71(3H, s), 3.74(2H, s), 4.63(1H, m), 5.37(2H, s), 6.47(1H, s), 7.06(1H, d, J=7.6Hz), 7.71(1H, d, J=7.6Hz), 7.75(1H, t, J=7.6Hz), 7.86(1H, m), 8.00(1H, t, J=7.6Hz), 8.27(1H, d, J=7.6Hz), 8.35(1H, m, J=7.6Hz), 10.53(1H, s), 12.63(1H, s)124 (solvent:DMSO-d.sub.6) 1.19(3H, t, J=7.6Hz), 2.59(3H, s), 2.65(2H, q, J=7.6Hz), 3.89(2H, s), 5.53(2H, s), 6.73(1H, s), 7.37(1H, d, J=7.9Hz), 7.51(1H, t, J=7.9Hz), 7.69(1H, s), 8.46(1H, d, J=7.9Hz), 9.13(1H, s), 9.37(1H, s), 11.96(1H, s), 12.50(1H, br), 12.54(1H, s)125 (solvent:CDCl.sub.3) 1.26(3H, t, J=7.6Hz), 1.31(3H, t, J= 7.3Hz), 2.60(3H, s), 2.69(2H, q, J=7.6Hz), 3.98(3H, s), 4.25(2H, q, J=7.3Hz), 5.39(2H, s), 6.47(1H, s), 7.15(1H, dd, J=8.3Hz, 2.0Hz), 7.39(1H, t, J=8.3Hz), 7.52(1H, s), 8.61(1H, dd, J=8.3Hz, 2.0Hz), 9.07(1H, s), 9.46(1H, s), 12.12(1H, s), 12.65(1H, s)______________________________________
TABLE 102__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________126 ##STR570##127 ##STR571##128 ##STR572##129 ##STR573##130 ##STR574##__________________________________________________________________________
TABLE 103______________________________________.sup.1 H-NMR .delta. ppm______________________________________126 (solvent:CDCl.sub.3) 1.28(3H, t, J=7.4Hz), 2.58(3H, s), 2.71(2H, q, J=7.4Hz), 3.02(2H, t, J=5.5Hz), 4.05(2H, t, J=5.5Hz), 5.34(2H, s), 6.49(1H, s), 6.98(1H, d, J=7.6Hz), 7.50(1H, s), 7.70(1H, d, J=7.9Hz), 7.72(1H, dd, J=7.9, 7.9Hz), 7.98(1H, d, J=7.9, 7.6Hz), 8.27(1H, d, J=7.6Hz), 8.30(1H, d, J=8.2Hz)127 (solvent:CDCl.sub.3) 1.10(3H, t, J=7.1Hz), 1.17(3H, t, J= 7.3Hz), 1.27(3H, t, J=8.1Hz), 2.59(3H, s), 2.71(2H, q, J= 7.2Hz), 2.84(1H, dd, J=16.8, 4.6Hz), 3.02(1H, dd, J=16.8, 4.3Hz), 3.75(2H, s), 4.00(2H, q, J=7.1Hz), 4.16(2H, q, J= 7.0Hz), 4.85(1H, dt, J=7.9, 4.6Hz), 5.39(2H, s), 6.49(1H, s), 7.05(1H, dd, J=7.6, 0.6Hz), 7.51(1H, s), 7.72(1H, d, J= 7.6Hz), 7.75(1H, dd, J=7.9, 7.9Hz), 7.99(1H, dd, J=7.6, 7.9Hz), 8.26(1H, dd, J=8.6, 1.0Hz), 8.34(1H, dd, J=8.2, 0.7Hz)128 (solvent:DMSO-d.sub.6) 0.90(3H, d, J=7.6Hz), 0.91(3H, d, J= 7.6Hz), 1.19(3H, t, J=7.3Hz), 2.07(1H, m), 2.58(3H, s), 2.65(2H, q, J=7.3Hz) 3.92(2H, ABq, J=21.8, 15.5Hz), 4.18 (1H, dd, J=8.3, 5.6Hz), 5.42(2H, s), 6.62(1H, s), 7.29 (1H, dd, J=8.3, 2.0Hz), 7.48(1H, t, J=8.3Hz), 7.68(1H, s), 7.85(1H, m), 8.20(2H, m), 8.45(1H, dd, J=8.3, 2.0Hz), 8.46 (1H, d, J=8.3Hz), 12.17(1H, s), 12.51(1H, s), 12.60(1H, s)129 (solvent:CDCl.sub.3) 0.88(3H, t, J=7.3Hz), 0.89(3H, t, J= 7.3Hz), 1.27(3H, t, J=7.6Hz), 2.18(1H, m), 2.59(3H, s), 2.71 (2H, q, J=7.6Hz) 3.65(3H, s), 4.04(2H, Abq, J=17.5, 13.2Hz), 4.40(1H, m), 5.36(2H, s) 6.45(1H, s), 7.18(1H, dd, J=8.3, 2.0Hz), 7.41(1H, t, J=8.3Hz), 7.51(1H, s), 7.74 (1H, d, J=7.9Hz), 8.00(1H, t, J=7.9Hz), 8.25(1H, d, J= 7.9Hz), 8.63(1H, dd, J=8.3, 2.0Hz), 8.78(1H, d, J=8.6Hz), 12.38(1H, s), 12.62(1H, s)130 (solvent:DMSO-d.sub.6) 1.10(3H, d, J=7.3Hz), 1.22(3H, t, J= 7.6Hz), 2.58(3H, s), 2.67(2H, q, J=7.6Hz), 3.76(2H, ABq, J=20.5, 14.9Hz), 4.17(1H, br), 4.26(1H, m), 4.95(1H, m), 5.47(2H, s), 6.63(1H, s), 7.20(1H, d, J=7.6Hz), 7.69(1H, s), 7.82(2H, m), 8.18(4H, m), 10.36(1H, s), 12.50(1H, br), 12.55 (1H, s)______________________________________
TABLE 104__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________131 ##STR575##132 ##STR576##133 ##STR577##134 ##STR578##135 ##STR579##__________________________________________________________________________
TABLE 105______________________________________.sup.1 H-NMR .delta. ppm______________________________________131 (solvent:CDCl.sub.3) 1.16(3H, d, J=7.3Hz), 1.26(3H, t, J= 7.6Hz), 2.57(3H, s), 2.69(2H, q, J=7.6Hz), 3.01(1H, br), 3.69 (3H, s), 4.05(2H, ABq, J=20.1Hz, 13.9Hz), 4.50(1H, m), 4.54(1H, m), 5.36(2H, s), 6.49(1H, s), 7.20(1H, dd, J=8.3Hz, 1.7Hz), 7.41(1H, t, J=8.3Hz), 7.48(1H, s), 7.72(1H, d, J= 7.9Hz), 7.98(1H, t, J=7.9Hz), 8.21(1H, d, J=7.9Hz), 8.51 (1H, d, J=8.6Hz), 8.60(1H, dd, J=8.3, 1.7Hz), 12.34(1H, s), 12.64(1H, s)132 (solvent:DMSO-d.sub.6) 1.19(3H, t, J=7.3Hz), 1.31(3H, d, J= 7.3Hz), 2.58(3H, s), 2.64(2H, q, J=7.6Hz), 3.85(2H, m), 4.24 (1H, m), 5.43(2H, s), 6.63(1H, s), 7.31(1H, dd, J=8.3, 1.7Hz), 7.47(1H, t, J=8.3Hz), 7.68(1H, s), 7.85(1H, m), 8.21 (2H, m), 8.46(1H, dd, J=8.3, 1.7Hz), 8.54(1H, d, J=7.9Hz), 12.15(1H, s), 12.50(1H, s), 12.55(1H, br)133 (solvent:DMSO-d.sub.6) 0.92(3H, t, J=7.6Hz), 1.20(3H, t, J= 7.6Hz), 1.6-1.9(1H, m), 2.58(3H, s), 2.65(2H, q, J=7.6Hz), 3.89(2H, ABq, J=20.8, 15.8Hz), 4.17(1H, m), 5.42(2H, s), 6.63(1H, s), 7.30(1H, dd, J=8.3Hz, 2.0Hz), 7.47(1H, t, J= 8.3Hz), 7.68(1H, s), 7.85(2H, m), 8.21(2H, m), 8.45(1H, dd, J=8.3, 2.0Hz), 8.50(1H, d, J=7.9Hz), 12.16(1H, s), 12.50 (1H, s), 12.55(1H, br)134 (solvent:CDCl.sub.3) 0.89(3H, t, J=7.3Hz), 1.27(3H, t, J= 7.6Hz), 1.70-1.85(2H, m), 2.59(3H, s), 2.71(2H, q, J=7.6Hz), 3.66(3H, s), 4.02(2H, ABq, J=18.8, 13.2Hz), 4.45(1H, m), 5.38(2H, s), 6.48(1H, s), 7.18(1H, dd, J=7.9, 2.0Hz), 7.41 (1H, t, J=7.9Hz), 7.50(1H, s), 7.75(1H, d, J=7.9Hz), 8.00 (1H, t, J=7.9Hz), 8.25(1H, d, J=7.9Hz), 8.61(1H, brd), 8.63 (1H, dd, J=7.9Hz, 2.0Hz), 12.33(1H, s), 12.63(1H, s)135 (solvent:DMSO-d.sub.6) 1.20(3H, t, J=7.6Hz), 2.58(3H, s), 2.65 (2H, q, J=7.6Hz), 2.7-2.9(2H, m), 3.87(2H, s), 4.58(1H, m), 5.43(2H, s), 6.64(1H, s), 7.30(1H, dd, J=8.3, 2.0Hz), 7.47(1H, t, J=8.3Hz), 7.68(1H, s), 7.84(1H, m), 8.21(1H, m), 8.46(1H, dd, J=8.3Hz, 2.0Hz), 8.61(1H, d, J=7.9Hz), 12.14 (1H, s), 12.51(1H, s), 12.55(2H, br)______________________________________
TABLE 106__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________136 ##STR580##137 ##STR581##138 ##STR582##139 ##STR583##140 ##STR584##__________________________________________________________________________
TABLE 107______________________________________.sup.1 H-NMR .delta. ppm______________________________________136 (solvent: CDCl.sub.3) 1.15(3H, t, J=7.3Hz), 1.17(3H, t, J= 7.3Hz), 1.27(3H, t, J=7.6Hz), 2.59(3H, s), 2.71(2H, q, J= 7.6Hz), 2.80-2.95(2H, m), 3.93-4.16(6H, m), 4.81(1H, m), 5.39(2H, s), 6.47(1H, s), 7.18(1H, d, J=8.3Hz), 7.41(1H, t, J=8.3Hz), 7.51(1H, s), 7.76(1H, d, J=7.9Hz), 8.01(1H, t, J=7.9Hz), 8.25(1H, d, J=7.9Hz), 8.62(1H, dd, J=8.3, 1.7Hz), 8.69(1H, d, J=7.9Hz), 12.31(1H, s), 12.61(1H, s)137 (solvent:DMSO-d.sub.6) 1.09(3H, d, J=7.6Hz), 1.20(3H, t, J= 7.6Hz), 2.58(3H, s), 2.66(2H, q, J=7.6Hz), 3.96(2H, ABq, J=20.8, 15.8Hz), 4.10(1H, br), 4.24(1H, m), 4.90(1H, m), 5.42(2H, s), 6.63(1H, s), 7.31(1H, dd, J=7.9, 2.0Hz), 7.48 (1H, t, J=7.9Hz), 7.68(1H, s), 7.85(1H, m), 8.17-8.30(3H, m), 12.16(1H, s), 12.50(1H, s), 12.55(1H, br)138 (solvent:CDCl.sub.3) 1.18(2H, d, J=6.6Hz), 1.27(3H, t, J= 7.6Hz), 2.58(3H, s), 2.69(2H, q, J=7.6Hz), 3.72(3H, s), 3.80 (2H, s), 4.34(4H, m), 4.61(1H, m), 5.37(2H, s), 6.49(1H, s), 7.06(1H, d, J=7.9Hz), 7.49(1H, s), 7.70(1H, d, J=7.9Hz), 7.76(1H, t, J=7.9Hz), 7.97(1H, t, J=7.9Hz), 8.25(1H, d, J= 7.9Hz), 8.29(1H, d, J=7.9Hz), 8.46(1H, brd, J=8.3Hz), 10.57(1H, s), 12.70(1H, s)139 (solvent:CDCl.sub.3) 1.27(3H, t, J=7.6Hz), 1.41(3H, d, J= 7.3Hz), 2.59(3H, s), 2.71(2H, q, J=7.6Hz), 3.66(3H, s), 4.01(2H, ABq, J=29.7Hz, 13.2Hz), 4.51(1H, m), 5.40(2H, s), 6.50(1H, s), 7.18(1H, dd, J=8.3, 2.0Hz), 7.41(1H, t, J= 8.3Hz), 7.50(1H, s), 7.75(1H, d, J=7.9Hz), 8.00(1H, t, J= 7.9Hz), 8.26(1H, d, J=7.9Hz), 8.52(1H, d, J=7.6Hz), 8.64(1H, dd, J=8.3, 2.0Hz), 12.31(1H, s), 12.63(1H, s)140 (solvent:DMSO-d.sub.6) 1.20(3H, t, J=7.6Hz), 1.90-2.52(4H, m), 2.58(3H, s), 2.66(2H, q, J=7.6Hz), 3.70(2H, m), 3.99(2H, ABq, J=29.7, 16.2Hz), 4.29(1H, m), 5.24(2H, s), 6.63(1H, s), 7.33(1H, dd, J=7.6, 2.0Hz), 7.47(1H, t, J= 8.3Hz), 7.68(1H, s), 7.85(1H, dd, J=5.6, 3.3Hz), 8.20(2H, s), 8.46(1H, dd, J=8.3, 2.0Hz), 12.14(1H, s), 12.51(1H,______________________________________ s)
TABLE 108__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________141 ##STR585##142 ##STR586##__________________________________________________________________________
TABLE 109______________________________________.sup.1 H-NMR .delta. ppm______________________________________141 (solvent:CDCl.sub.3) 1.27(3H, t, J=7.6Hz), 1.9-2.3(4H, m), 2.59(3H, s), 2.71(2H, q, J=7.6Hz), 3.73(3H, s), 3.6-3.9(2H, m), 3.87(2H, m), 4.55(1H, m), 5.33(2H, s), 6.47(1H, s), 7.18(1H, d, J=7.9Hz), 7.51(1H, s), 7.69(1H, d, J=7.9Hz), 7.74(1H, t, J=7.9Hz), 7.98(1H, t, J=7.9Hz), 8.27(1H, d, J= 7.9Hz), 8.31(1H, d, J=7.9Hz), 10.34(1H, s), 12.67(1H, s)142 (solvent:CDCl.sub.3) 1.27(3H, t, J=7.6Hz), 1.9-2.3(4H, m), 2.58(3H, s), 2.70(2H, q, J=7.6Hz), 3.74(3H, s), 3.7-3.9(2H, m), 3.90(1H, d, J=15.8Hz), 4.26(1H, d, J=15.8Hz), 4.61(1H, m), 5.35(2H, s), 6.46(1H, s), 7.25(1H, brd), 7.37(1H, t, J= 7.9Hz), 7.50(1H, s), 7.73(1H, d, J=7.9Hz), 7.98(1H, t, J= 7.9Hz), 8.24(1H, d, J=7.9Hz), 8.59(1H, d, J=7.9Hz), 12.29 (1H, s), 12.65(1H, s)______________________________________
TABLE 110__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________143 ##STR587##144 ##STR588##145 ##STR589##146 ##STR590##147 ##STR591##__________________________________________________________________________
TABLE 111______________________________________.sup.1 H-NMR .delta. ppm______________________________________143 (solvent:CDCl.sub.3) 1.26(3H, t, J=7.4Hz), 1.27(3H, t, J= 7.4Hz), 1.30(3H, t, J=7.0Hz), 2.58(3H, t), 2.69(2H, q, J= 7.4Hz), 2.97(1H, dd, J=16.8, 4.6Hz), 3.13(1H, dd, J=16.8, 4.0Hz), 4.19(2H, qd, J=7.3, 3.0Hz), 4.27(2H, q, J=7.3, 3.0Hz) 5.06(1H, td, J=8.3, 5.0Hz), 5.27(1H, s), 6.46(1H, s), 7.49(1H, s), 7.64(1H, dd, J=7.6, 1.0Hz), 7.91(1H, dd, J=7.6, 7.6Hz), 8.14(1H, dd, J=7.6, 1.0Hz)144 (solvent:CDCl.sub.3) 1.26(3H, t, J=7.6Hz), 1.32(3H, t, J= 7.3Hz), 2.58(3H, s), 2.68(2H, q, J=7.6Hz), 4.2-4.3(4H, m), 5.26(2H, s), 6.45(1H, s), 7.49(1H, s), 7.64(1H, d, J=7.6Hz), 7.92(1H, dd, J=6.9, 7.6Hz), 8.15(1H, d, J=6.9Hz), 12.66 (1H, s)145 (solvent:CDCl.sub.3) 1.25(3H, t, J=7.6Hz), 1.28(3H, t, J= 7.3Hz), 2.6-2.7(4H, m), 3.7-3.8(2H, m), 4.1-4.2(2H, q, J= 7.3Hz), 5.24(2H, s), 6.45(1H, s), 7.49(1H, s), 7.61(1H, d, J= 7.9Hz), 7.90(1H, dd, J=6.6, 7.9Hz), 8.14(1H, d, J=6.6Hz), 8.42(1H, br), 12.66(1H, s)146 (solvent:CDCl.sub.3) 1.02(6H, dd, J=4.0Hz, 6.9Hz, 1.26(3H, t, J=7.6Hz), 2.2-2.4(1H, m), 2.58(3H, s), 2.69(2H, q, J= 7.6Hz), 3.78(3H, s), 4.75(1H, dd, J=5.3, 9.2Hz), 5.29(2H, s), 6.49(1H, s), 7.50(1H, s), 7.64(1H, d, J=7.9Hz), 7.91(1H, dd, J=7.9, 7.9Hz), 8.15(1H, d, J=7.9Hz), 8.44(1H, d, J= 9.2Hz), 12.66(1H, s)147 (solvent:CDCl.sub.3) 1.25(3H, t, J=7.6Hz), 2.58(3H, s), 2.68(2H, q, J=7.6Hz), 3.85(3H, s), 4.0-4.2(2H, m), 4.8-4.9(1H, m), 5.29(2H, s), 6.51(1H, s), 7.49(1H, s), 7.65(1H, d, J=7.6Hz), 7.92(1H, dd, J=7.6, 7.9Hz), 8.15(1H, d, J=7.9Hz), 8.80(1H, d, J=7.9Hz), 12.70 (1H, s)______________________________________
TABLE 112__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________148 ##STR592##149 ##STR593##150 ##STR594##151 ##STR595##152 ##STR596##__________________________________________________________________________
TABLE 113______________________________________.sup.1 H-NMR .delta. ppm______________________________________148 (solvent:CDCl.sub.3) 1.26(3H, t, J=7.6Hz), 1.32(3H, t, J= 7.3Hz), 2.0-2.2(1H, m), 2.12(3H, s), 2.3-2.4(1H, m), 2.5-2.7 (4H, m), 2.58(3H, s), 4.26(2H, q, J=7.3Hz), 4.8-5.0(1H, m), 5.29(2H, s), 6.47(1H, s), 7.50(1H, s), 7.64(1H, dd, J=1.0, 7.6Hz), 7.91(1H, dd, J=7.6, 7.6Hz), 8.14(1H, dd, J=1.0Hz, 7.6Hz), 8.52(1H, d, J=8.6Hz), 12.66(1H, s)149 (solvent:CDCl.sub.3) 1.25(3H, t, J=7.6Hz), 2.58(3H, s), 2.67(2H, q, J=7.6Hz), 3.26(2H, dd, J=1.8Hz, 6.3Hz), 3.75(3H, s), 5.07(1H, dt, J=8.3, 6.3Hz), 5.22(2H, s), 6.45(1H, s), 7.1-7.4(5H, m), 7.50(1H, s), 7.62(1H, d, J=7.3Hz), 7.89(1H, dd, J=6.9Hz, 7.3Hz), 8.11(1H, d, J=6.9Hz), 8.41(1H, d, J=8.3Hz), 12.67(1H, s)150 (solvent:CDCl.sub.3) 1.25(3H, t, J=7.6Hz), 2.58(3H, s), 2.68(2H, q, J=7.6Hz), 3.1-3.2(2H, m), 3.76(3H, s), 5.02(1H, dt, J=8.6Hz, 5.9Hz), 5.21(2H, d, J=2.0Hz), 6.09(1H, s), 6.42(1H, s), 6.76(1H, dd, J=2.3Hz, 8.9Hz), 7.02(1H, d, J= 8.9Hz), 7.50(1H, s), 7.61(1H, d, J=7.6Hz), 7.88(1H, dd, J= 7.5Hz, 7.6Hz), 8.10(1H, d, J= 7.5Hz), 8.40(1H, d, J=8.6Hz), 12.63(1H, s)151 (solvent:CDCl.sub.3) 1.25(3H, t, J=7.6Hz), 2.58(3H, s), 2.68(2H, q, J=7.6Hz), 3.30(2H, d, J=5.6Hz), 3.79(3H, s), 5.0-5.1(1H, m), 5.27(2H, d, J=4.6Hz), 6.42(1H, s), 6.86(1H, d, J=1.3Hz), 7.49(1H, s), 7.6-7.7(2H, m), 7.89(1H, dd, J=7.6Hz, 7.6Hz), 8.12(1H, dd, J=1.0Hz, 7.9Hz), 8.8-8.9(1H, m), 12.80(1H, s)152 (solvent:CDCl.sub.3) 1.26(3H, t, J=7.6Hz), 1.57(3H, d, J= 6.9Hz), 2.58(3H, s), 2.69(2H, q, J=7.6Hz), 3.80(3H, s), 4.82 (1H, dq, J=6.9Hz, 8.3Hz), 5.28(2H, s), 6.47(1H, s), 7.50(1H, s), 7.63(1H, dd, J=1.0Hz, 7.9Hz), 7.91(1H, dd, J=7.9Hz, 7.9Hz), 8.14(1H, dd, J=1.0, 7.9Hz), 8.43(1H, d, J=8.3Hz), 12.66(1H, s)______________________________________
TABLE 114__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________153 ##STR597##154 ##STR598##155 ##STR599##156 ##STR600##157 ##STR601##__________________________________________________________________________
TABLE 115______________________________________.sup.1 H-NMR .delta. ppm______________________________________153 (solvent:CDCl.sub.3) 1.26(3H, t, J=7.6Hz), 1.57(3H, d, J= 7.3Hz), 2.58(3H, s), 2.69(2H, q, J=7.6Hz), 3.80(3H, s), 4.82 (1H, dq, J=7.3Hz, 7.9Hz), 5.28(2H, s), 6.45(1H, s), 7.50(1H, s), 7.63(1H, d, J=7.6Hz), 7.91(1H, dd, J=7.6, 7.6Hz), 8.14(1H, d, J=7.6Hz), 8.43(1H, d, J=7.9Hz), 12.66(1H, s)154 (solvent:CDCl.sub.3) 1.26(3H, t, J=7.6Hz), 2.1-2.5(4H, m), 2.58(3H, s), 2.69(2H, q, J=7.6Hz), 3.66(3H, s), 3.70(3H, s), 4.8-4.9(1H, m), 5.29(2H, s), 6.48(1H, s), 7.50(1H, s), 7.64(1H, dd, J=1.0Hz, 7.6Hz), 7.91(1H, dd, J=7.6Hz, 7.6Hz), 8.13(1H, dd, J=1.0, 7.6Hz), 8.47(1H, d J=8.6Hz), 12.65(1H, s)155 (solvent:CDCl.sub.3) 1.25(3H, t, J=7.3Hz), 1.26(3H, t, J= 7.6Hz), 2.58(3H, s), 2.69(2H, q, J=7.6Hz), 3.68(2H, d, J= 1.0Hz), 4.17(2H, q, J=7.3Hz), 4.42(2H, d, J=6.3Hz), 5.26 (2H, s), 6.45(1H, s), 6.82(1H, t, J=1.0Hz), 7.50(1H, s), 7.69(1H, d, J=7.9Hz), 7.96(1H, dd, J=7.9Hz, 8.9Hz), 8.63 (1H, br), 9.80(1H, br), 12.67(1H, s)156 (solvent:CDCl.sub.3) 1.25(3H, t, J=7.6Hz), 2.58(3H, s), 2.68(2H, q, J=7.6Hz), 2.97(1H, dd, J=6.3Hz, 15.8Hz), 3.09(1H, dd, J=6.6, 15.8Hz), 3.64(3H, s), 5.27(2H, s), 5.64 (1H, ddd, J=6.3Hz, 6.6Hz, 8.9Hz), 6.49(1H, s), 7.2-7.5(5H, m), 7.49(1H, s), 7.63(1H, d, J=7.3Hz), 7.90(1H, dd, J= 7.3Hz. 7.3Hz), 8.15(1H, d, J=7.3Hz), 8.80(1H, d, J=8.9Hz), 12.66(1H, s)157 (solvent:CDCl.sub.3) 1.25(3H, t, J=7.6Hz), 1.9-2.1(2H, m), 2.45(2H, t, J=7.6Hz), 2.58(3H, s), 2.68(2H, q, J=7.6Hz), 3.54(2H, m), 3.68(3H, s), 5.25(2H, s), 6.47(1H, s), 7.50(1H, s), 7.61(1H, d, J=7.6Hz), 7.90(1H, dd, J=7.6Hz, 7.9Hz), 8.10(1H, br), 8.15(1H, d, J=7.9Hz)______________________________________
TABLE 116__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________158 ##STR602##159 ##STR603##160 ##STR604##161 ##STR605##162 ##STR606##__________________________________________________________________________
TABLE 117______________________________________.sup.1 H-NMR .delta. ppm______________________________________158 (solvent:CDCl.sub.3) 1.25(3H, t, J=7.6Hz), 1.3-1.5(2H, m), 1.6-1.8(4H, m), 2.34(2H, t, J=7.6Hz), 2.58(3H, s), 2.68(2H, q, J=7.6Hz), 3.4-3.5(2H, m), 3.67(3H, s), 5.25(2H, s), 6.47(1H, s), 7.49(1H, s), 7.51(1H, d, J=7.9Hz), 7.90(1H, dd, J=7.9Hz, 7.9Hz), 8.02(1H, br), 8.16(1H, d, J=7.9Hz), 12.67(1H, s)159 (solvent:DMSO-d.sub.6) 1.19(3H, t, J=7.6Hz), 2.52(3H, s), 2.60 (2H, q, J=7.6Hz), 3.5-3.7(2H, m), 4.6-4.8(1H, m), 5.36(2H, s), 5.57(1H, d, J=4.3Hz), 6.58(1H, s), 6.6-6.7(1H, m), 6.8- 6.9(2H, m), 7.1-7.2(1H, m), 7.7-7.8(2H, m), 7.9-8.2(2H, m), 8.5-8.6(1H, m), 9.34(1H, s), 12.56(1H, s)160 (solvent:DMSO-d.sub.6) 1.25(3H, t, J=7.6Hz), 2.59(3H, s), 2.67 (2H, q, J=7.6Hz), 2.73(1H, t, J=5.4Hz), 3.6-3.7(2H, m), 3.8-3.9(2H, m), 5.25(2H, m), 6.49(1H, s), 7.49(1H, s), 7.62(1H, d, J=7.6Hz), 7.91(1H, dd, J=7.6Hz, 7.6Hz), 8.16(1H, d, J=7.6Hz), 8.40(1H, br). 12.69(1H, s)161 (solvent:DMSO-d.sub.6) 1.24(3H, t, J=7.6Hz), 2.59(3H, s), 2.68(2H, q, J=7.6Hz), 3.6-4.0(9H, m), 5.25(2H, s), 5.84(1H, t, J=4.6Hz), 6.43(1H, s), 7.49(1H, s), 7.62(1H, d, J=7.6Hz), 7.81(1H, d, J=7.6Hz), 7.95(1H, dd, J=7.6Hz, 7.6Hz), 12.62(1H, s)162 (solvent:DMSO-d.sub.6) 1.25(3H, t, J=7.6Hz), 1.8-1.9(2H, m), 2.58(3H, s), 2.67(2H, q, J=7.6Hz), 3.30(1H, t, J=6.4Hz), 5.25(2H, s), 6.50(1H, s), 7.63(1H, d, J=7.6Hz), 7.91(1H, dd, J=7.6Hz, 7.6Hz), 8.16(1H, d, J=7.6Hz), 8.30(1H, br), 12.71(1H, s)______________________________________
TABLE 118______________________________________Ex.No. Structural formula______________________________________163 ##STR607##164 ##STR608##165 ##STR609##166 ##STR610##167 ##STR611##______________________________________
TABLE 119______________________________________.sup.1 H-NMR .delta. ppm______________________________________163 (solvent:DMSO-d.sub.6) 1.25(3H, t, J=7.6Hz), 1.32(3H, t, J= 7.1Hz), 2.57(3H, s), 2.68(2H, q, J=7.6Hz), 3.4-4.0(6H, m), 5.25(2H, s), 6.45(1H, s), 7.49(1H, s), 7.5-7.9(3H, m), 12.61 (1H, s)164 (solvent:CDCl.sub.3) 1.22(3H, t, J=7.4Hz), 1.32(3H, t, J= 7.1Hz), 2.57(3H, s), 2.63(2H, q, J=7.4Hz), 4.26(2H, s), 4.27(2H, q, J=7.1Hz), 5.13(2H, s), 6.44(1H, s), 7.46(1H, s), 7.49(1H, dd, J=7.6, 7.6Hz), 7.59(1H, d, J=7.6Hz), 7.77(1H, d, J=7.6Hz), 7.90(1H, s)165 (solvent:CDCl.sub.3) 1.22(3H, t, J=7.4Hz), 1.54(2H, d, J= 7.0Hz), 2.57(3H, s), 2.63(2H, q, J=7.4Hz), 3.80(3H, s), 4.82(1H, q, J=7.0Hz), 5.14(2H, s), 6.44(1H, s), 7.46(1H, s), 7.48(1H, dd, J=7.6, 7.6Hz), 7.58(1H, q, J=7.6 Hz), 7.76(1H, d, J=7.6Hz), 7.88(1H, s)166 (solvent:CDCl.sub.3) 1.22(3H, t, J=7.6Hz), 1.26(3H, t, J= 7.1Hz), 1.29(3H, t, J=7.1Hz), 2.57(3H, s), 2.64(2H, q, J= 7.4Hz), 2.97(1H, dd, J=17.2, 4.3Hz), 3.14(1H, dd, J=17.2, 4.3Hz), 4.16(2H, q, J=7.1Hz), 4.27(2H, q, J=7.1Hz), 5.04 (1H, td, J=4.3, 7.9Hz), 5.15(1H, s), 6.45(1H, s), 7.46(1H, s), 7.49(1H, dd, J=7.6, 7.6Hz), 7.59(1H, d J=7.6Hz), 7.77(1H, d, J=7.6Hz, 7.90(1H, s)167 (solvent:CDCl.sub.3) 1.22(3H, t, J=7.4Hz), 2.57(3H, s), 2.63(2H, q, J=7.4Hz), 3.83(3H, s), 4.1-4.2(2H, br), 4.89(1H, dt, J=7.3, 3.6Hz), 5.14(2H, s), 6.44(1H, s), 7.47(1H, s), 7.49(1H dd, J=7.6, 7.6Hz), 7.60(1H, d, J=7.6Hz), 7.80(1H, d, J=7.6Hz), 7.91(1H, s)______________________________________
TABLE 120______________________________________Ex. No. Structural formula______________________________________168 ##STR612##169 ##STR613##170 ##STR614##171 ##STR615##172 ##STR616##______________________________________
TABLE 121______________________________________.sup.1 H-NMR .delta. ppm______________________________________168 (solvent:CDCl.sub.3) 0.98(3H, t, J=7.3Hz), 1.27(3H, t, J= 7.3Hz), 1.30(3H, t, J=7.1Hz), 1.5-1.7(2H, m), 2.58(3H, s), 2.76(2H, t, J=7.6Hz), 2.98(1H, dd, J=16.8, 4.9Hz), 3.14(1H, dd, J=16.8, 4.9Hz), 4.1-4.4(4H, m), 5.06(1H, dt, J=8.6, 4.9Hz), 5.32(2H, s), 6.50(1H, d, J=8.9Hz), 7.61(1H, d, J=8.9Hz), 7.66(1H, d, J=8.9Hz), 7.66(1H, d, J=7.9Hz), 7.91(1H, dd, J=7.6, 7.9Hz), 8.13(1H, d, J=7.6Hz)169 (solvent:CDCl.sub.3) 1.02(3H, t, J=7.4Hz), 1.27(3H, t, J= 7.1Hz), 1.30(3H, t, J=7.1Hz), 1.6-1.7(2H, m), 2.62(3H, t), 2.74(2H, t, J=7.9Hz), 2.97(1H, dd, J=17.0, 4.9Hz), 3.13(1H, dd, J=17.0, 4.9Hz), 4.1-4.4(4H, m), 5.06(1H, dt, J=8.3, 4.9Hz), 5.29(2H, s), 6.74(1H, d, J=8.8Hz), 7.57(1H, d, J=8.8Hz), 7.66(1H, d, J=7.9Hz), 7.91(1H, dd, J=7.6, 7.9Hz), 8.14(1H, d, J=7.6Hz)170 (solvent:CDCl.sub.3) 1.02(3H, t, J=7.3Hz), 1.32(3H, t, J= 7.3Hz), 1.56(3H, d, J=7.3Hz), 1.6-1.7(2H, m), 2.62(3H, s), 2.75(2H, t, J=7.9Hz), 3.78(3H, s), 4.26(2H, q, J=7.2Hz), 4.79(1H, qd, J=7.8, 7.8Hz), 5.29(2H, s), 6.73(1H, d, J= 7.6Hz), 7.57(1H, d J=8.6Hz), 7.64(1H, d, J=7.9Hz), 7.91(1H, dd, J=7.6, 7.9Hz), 8.14(1H, d, J=7.6Hz)171 (solvent:CDCl.sub.3) 1.24(3H, t, J=7.2Hz), 1.32(3H, t, J= 7.1Hz), 1.56(3H, d, J=1.0Hz), 2.58(3H, s), 2.69(2H, q, J= 7.5Hz), 3.88(3H, s), 4.26(2H, q, J=7.2Hz), 4.81(1H, qd, J= 7.7, 7.7Hz), 5.32(2H, s), 6.51(1H, s), 7.72(1H, s), 7.70(1H, d, J=8.3Hz), 7.93(1H, dd, J=7.9, 7.6Hz), 8.15(1H, d, J=7.9Hz)172 (solvent:CDCl.sub.3) 1.24(3H, t, J=7.5Hz), 1.6-2.2(4H, m), 2.57(3H, s), 2.67(2H, q, J=7.5Hz), 3.5-5.4(7H, m), 6.44-6.46(2H, m), 7.5-8.0(4H, m)______________________________________
TABLE 122__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________173 ##STR617##174 ##STR618##175 ##STR619##176 ##STR620##177 ##STR621##__________________________________________________________________________
TABLE 123______________________________________.sup.1 H-NMR .delta. ppm______________________________________173 (solvent:CDCl.sub.3) 1.25(3H, t, J=7.5Hz), 1.7-2.1(5H, m), 2.57 (3H, s), 2.67(2H, q, J=7.5Hz), 3.0-3.3(2H, m), 3.72(3H, s), 3.8-4.0(2H, m), 4.5-4.7(2H, m), 5.24(2H, s), 6.44(1H, s), 7,48(1H, s), 7.53(1H, d, J=7.6Hz), 7.56(1H, d, J=7.6Hz), 7.84(1H, dd, J=7.9, 7.9Hz)174 (solvent:CDCl.sub.3) 1.25(3H, td, J=7.6, 2.0Hz), 1.5-2.0(4H, m), 2.57(3H, s), 2.68(2H, q, J=7.6Hz), 3.61(1.5H, s), 3.73(1.5H, s), 2.5-5.0(5H, m), 5.24(2H, s), 6.44(1H, s), 7,48(1H, s), 7.5-8.0(3H, m)175 (solvent:CDCl.sub.3) 1.26(3H, t, J=7.4Hz), 1.38(2H, d, J= 6.9Hz), 2.58(3H, s), 2.5-2.7(4H, m), 3.72(3H, s), 4.5-4.6(1H, m), 5.27(2H, s), 6.48(1H, s), 7.49(1H, s), 7.61(1H, d, J= 7.9Hz), 7.89(1H, dd, J=7.9, 7.6Hz), 8.15(1H, d, J=7.6Hz)176 (solvent:CDCl.sub.3) 1.22(3H, t, J=6.9Hz), 1.25(3H, t, J= 7.1Hz), 1.29(3H, t, J=7.1Hz), 2.57(3H, s), 2.68(2H, q, J= 7.4Hz), 2.78(1H, t, J=7.1Hz), 3.44(1H, q, J=7.1Hz), 3.58 (1H, q, J=7.1Hz), 3.70(1H, t, J=7.4Hz), 3.79(1H, t, J= 7.4Hz), 4.10(1H, q, J=7.1Hz), 4.18(1H, q, J=7.1Hz), 5.21 (1H, s), 5.23(1H, s), 6.43(1H, s), 7.48(1H, s), 7.5-7.9(3H, m), 2.84(1H, t, J=7.1Hz)177 (solvent:CDCl.sub.3) 1.25(3H, t, J=7.4Hz), 1.29(3H, d, J= 6.3Hz), 2.58(3H, s), 2.69(2H, q, J=7.4Hz), 4.4-4.6(1H, m), 4.7-4.9(1H, m), 5.30(2H, s), 6.50(1H, s), 7.50(1H, s), 7.66 (1H, d, J=7.6Hz), 7.93(1H, dd, J=7.6, 7.6Hz), 8.13(1H, d, J=7.6Hz)______________________________________
TABLE 124______________________________________Ex. No. Structural formula______________________________________178 ##STR622##______________________________________
TABLE 125______________________________________.sup.1 H-NMR .delta. ppm______________________________________178 (solvent:CDCl.sub.3) 1.23(1.2H, t, J=7.6Hz), 1.26(1.8H, t, J= 7.6Hz), 2.1-2.6(2H, m), 2.59(3H, s), 2.8-3.0(2H, m), 3.8-4.8 (3H, m), 5.3-5.4(3H, m), 6.44(0.6H, s), 6.48(0.4H, s), 7.5-8.1 (3H, s)______________________________________
TABLE 126______________________________________.sup.1 H-NMR .delta.ppm______________________________________179 ##STR623##180 ##STR624##181 ##STR625##182 ##STR626##183 ##STR627##______________________________________
TABLE 127______________________________________.sup.1 H-NMR .delta. ppm______________________________________179 (solvent:CD.sub.3 OD/CDCl.sub.3 (1/4)) 1.26(3H, t, J=7.4Hz), 2.60 (3H, s), 2.70(2H, q, J=7.4Hz), 2.97(1H, dd, J=17.5, 4.8Hz), 3.15(1H, dd, J=17.5, 4.8Hz), 5.00(1H, t, J=8.9Hz), 5.29(2H, s), 6.47(1H, s), 7.53(1H, s), 7.68(1H, d, J=7.9Hz), 7.95(1H, dd, J=7.9, 7.6Hz), 8.11(1H, d, J=7.6Hz)180 (solvent:d.sub.6 -DMSO) 1.18(3H, t, J=7.6Hz), 2.58(3H, S), 2.62(2H, q, J=7.6Hz), 4.00(2H, d, J=5.9Hz), 5.36(2H, s), 6.57(1H, s), 7.69(1H, s), 7.73(1H, d, J=6.3Hz), 8.01(1H, d, J=6.3Hz), 8.10(1H, dd, J=6.3Hz, 6.3Hz), 8.88(1H, t, J=5.9Hz), 12.55(1H, s)181 (solvent:d.sub.6 -DMSO) 1.18(3H, s, J=7.6Hz), 2.58(3H, s), 2.61(2H, q, J=7.6Hz), 2.69(2H, q, J=7.6Hz), 3.4-3.5(2H, m), 5.35(2H, s), 6.57(1H, s) 7.69(1H, s), 7.70(1H, dd, J= 1.0Hz, 7.6Hz), 7.99(1H, dd, J=1.0Hz, 7.6Hz), 8.07(1H, dd, J=7.6Hz, 7.6Hz), 8.72(1H, t, J=5.9Hz), 12.54(1H, br)182 (solvent:d.sub.6 -DMSO) 0.91(6H, t, J=6.4Hz), 1.18(3H, t, J= 7.6Hz), 2.1-2.2(1H, m), 2.57(3H, s), 2.63(1H, q, J=7.6Hz), 4.41(1H, dd, J=5.1Hz, 8.9Hz), 5.42(2H, s), 6.63(1H, s), 7.68(1H, s), 7.76(1H, d, J=6.6Hz), 8.01(1H, d, J=6.9Hz), 8.11(1H, dd, J=6.6Hz, 6.9Hz), 8.38(1H, d, J=8.9Hz), 12.55(1H, s)183 (solvent:d.sub.6 -DMSO) 1.19(3H, t, J=7.6Hz), 2.58(3H, s), 2.63(2H, q, J=7.6Hz), 3.77(1H, dd, J=3.6Hz, 10,9Hz), 3.91(1H, dd, J=3.6Hz, 10.9Hz), 4.4-4.5(1H, s), 5.39(2H, s) 6.61(1H, s), 7.69(1H, s), 7.75(1H, d, J=7.6Hz), 8.03(1H, dd, J=1.0Hz, 7.6Hz), 8.11(1H, dd, J=7.6Hz, 7.6Hz), 8.63(1H, d, J=8.3Hz), 12.55(1H, s)______________________________________
TABLE 128__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________184 ##STR628##185 ##STR629##186 ##STR630##187 ##STR631##188 ##STR632##__________________________________________________________________________
TABLE 129______________________________________.sup.1 H-NMR .delta. ppm______________________________________184 (solvent:d.sub.6 -DMSO) 1.18(3H, t, J=7.6Hz), 2.04(3H, s), 2.1-2.2(2H, m), 2.4-2.5(2H, m), 2.58(3H, s), 2.62(2H, q, J= 7.6Hz), 4.5-4.6(1H, m), 5.40(2H, s), 6.60(1H, s), 7.69(1H, s), 7.74(1H, d, J=7.6Hz), 7.99(1H, d, J=6.6Hz), 8.09(1H, dd, J=6.6Hz, 7.6Hz), 8.74(1H, d, J=8.2Hz), 12.55 (1H, s)185 (solvent:d.sub.6 -DMSO) 1.16(3H, t, J=7.6Hz), 2.59(3H, s), 2.63(2H, q, J=7.6Hz), 3.1-3.4(2H, m), 4.6-4.7(1H, m), 5.34 (2H, s), 6.60(1H, s), 7.1-7.3(5H, m), 7.68(1H, s), 7.71(1H, d, J=7.6Hz), 7.97(1H, dd, J=1.0Hz, 7.6Hz), 8.07(1H, dd, J= 7.6Hz, 7.6Hz), 8.61(1H, d, J=8.2Hz), 12.56(1H, s)186 (solvent:d.sub.6 -DMSO) 1.17(3H, t, J=7.6Hz), 2.58(3H, s), 2.61 (2H, q, J=7.6Hz), 3.5-3.6(2H, m), 4.6-4.7(1H, m), 5.36(1H, s), 6.62(2H, d, J=8.5Hz), 6.99(2H, d, J=8.5Hz), 7.69(1H, s), 7.73(1H, dd, J=1.0Hz, 7.6Hz), 7.96(1H, dd, J=1.0Hz, 7.6Hz) 8.08(1H, dd, J=7.6Hz, 7.6Hz), 8.52(1H, d, J= 8.3Hz), 9.21(1H, br), 12.56(1H, s)187 (solvent:d.sub.6 -DMSO) 1.17(3H, t, J=7.6Hz), 2.58(3H, s), 2.62(2H, q, J=7.6Hz), 3.20(2H, d, J=6.3Hz), 4.7-4.8(1H, m), 5.37(2H, s), 6.60(1H, s), 7.12(1H, s), 7.69(1H, s), 7.72(1H, d, J=7.6Hz), 7.98(1H, dd, J=0.7Hz, 7.6Hz) 8.08(1H, dd, J=7.6Hz, 7.6Hz), 8.28(1H, s) 8.99(1H, d, J=8.3Hz), 12.54(1H, br),188 (solvent:d.sub.6 -DMSO) 1.89(3H, t, J=7.6Hz), 1.43(3H, d, J= 7.3Hz), 2.58(3H, s), 2.63(2H, q, J=7.6Hz), 4.4-4.5(1H, m), 5.39(2H, s), 6.59(1H, s), 7.69(1H, s), 7.73(1H, d, J=7.6Hz), 8.00(1H, d, J=7.6Hz), 8.09(1H, dd, J=7.6Hz, 7.6Hz), 8.67(1H, d, J=7.9Hz), 12.55(1H, s)______________________________________
TABLE 130__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________189 ##STR633##190 ##STR634##191 ##STR635##192 ##STR636##193 ##STR637##__________________________________________________________________________
TABLE 131______________________________________.sup.1 H-NMR .delta. ppm______________________________________189 (solvent:d.sub.6 -DMSO) 1.89(3H, t, J=7.6Hz), 1.43(3H, d, J= 7.3Hz), 2.58(3H, s), 2.63(2H, q, J=7.6Hz), 4.4-4.5(1H, m), 5.39(2H, s), 6.59(1H, s), 7.69(1H, s), 7.73(1H, d, J=7.6Hz), 8.00(1H, d, J=7.6Hz), 8.09(1H, dd, J=7.6Hz, 7.6Hz), 8.67(1H, d, J=7.9Hz), 12.55(1H, s)190 (solvent:d.sub.6 -DMSO) 1.86(3H, t, J=7.6Hz), 1.9-2.3(4H, m), 2.58(3H, s), 2.63(2H, q, J=7.6Hz), 4.4-4.5(1H, m), 5.40(2H, s), 6.60(1H, s), 7.69(1H, s), 7.73(1H, d, J=7.6Hz), 8.00(1H, d, J=7.6Hz), 8.10(1H, dd, J=7.6Hz, 7.6Hz), 8.70(1H, d, J=8.6Hz), 12.55(1H, s)191 (solvent:d.sub.6 -DMSO) 1.19(3H, t, J=7.6Hz), 2.58(3H, s), 2.63(2H, q, J=7.6Hz), 3.60(2H, s), 4.24(2H, d, J=5.9Hz), 5.38(2H, s), 6.58(1H, s), 6.96(1H, s), 7.70(1H, s), 7.75(1H, d, J=7.6Hz), 8.02(1H, d, J=7.6Hz), 8.10(1H, dd, J=7.6Hz, 7.6Hz), 8.98(1H, d, J=5.9Hz), 12.34(1H, br), 12.55(1H, s)192 (solvent:d.sub.6 -DMSO) 1.17(3H, t, J=7.6Hz), 2.58(3H, s), 2.62(2H, q, J=7.6Hz), 2.88(1H, dd, J=6.3Hz, 16.2Hz), 4.0-4.2(1H, m), 5.39(2H, s), 5.4-5.5(1H, m), 6.60(1H, s), 7.2- 7.7(5H, m), 7.69(1H, s), 7.72(1H, d, J=7.6Hz), 7.98(1H, d, J=7.3Hz), 8.07(1H, dd, J=7.3Hz, 7.6Hz), 9.13(1H, d, J=8.9Hz), 12.32(1H, br), 12.56(1H, s)193 (solvent:d.sub.6 -DMSO) 1.18(3H, t, J=7.6Hz), 1.7-1.8(2H, m), 2.26(2H, t, J=7.6Hz), 2.58(3H, s), 2.62(2H, q, J=7.6Hz), 3.3-3.5(2H, m), 5.36(2H, s), 6.57(1H, s), 7.69(1H, s), 7.70(1H, d, J=7.6Hz), 7.98(1H, d, J=7.6Hz), 8.06(1H, dd, J=7.6Hz, 7.6Hz), 8.68(1H, d, J=5.6Hz), 12.00 (1H, br), 12.55(1H, br)______________________________________
TABLE 132__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________194 ##STR638##195 ##STR639##196 ##STR640##197 ##STR641##198 ##STR642##__________________________________________________________________________
TABLE 133______________________________________.sup.1 H-NMR .delta. ppm______________________________________194 (solvent:DMSO-d.sub.6) 1.18(3H, t, J=7.6Hz), 1.2-1.3(2H, m), 1.5-1.7(4H, m), 2.21(2H, t, J=7.3Hz), 2.58(3H, s), 2.62(2H, q, J=7.6Hz), 5.36(2H, s), 6.57(1H, s), 7.68(1H, d, J=7.6Hz), 7.69(1H, s), 7.98(1H, d, J=7.6Hz), 8.06(1H, dd, J=7.6Hz, 7.6Hz), 8.61(1H, m), 12.55(1H, br)195 (solvent:CD.sub.3 OD/CDCl.sub.3 (1/4)) 1.21(3H, t, J=7.6Hz), 2.58 (3H, s), 2.64(2H, q, J=7.6Hz), 4.18(2H, d, J=1.7Hz), 5.16 (2H, s), 6.46(1H, s), 7.49(1H, s), 7.50(1H, dd, J=7.6, 7.6Hz), 7.61(1H, d, J=7.6Hz), 7.81(1H, d, J=7.6Hz), 7.91(1H, s),196 (solvent:CD.sub.3 OD:CDCl.sub.3 =1:4) 1.22(3H, t, J=7.4Hz), 1.55(3H, d, J=6.9Hz), 2.58(3H, s), 2.64(2H, q, J=7.4Hz), 4.72(1H, td, J=5.9, 7.3Hz), 5.17(2H, s), 6.46(1H, s), 7.50(1H, dd, J=7.9, 7.6Hz), 7.61(1H, d, J=7.9Hz), 7.80(1H, d, J=7.6Hz), 7.90(1H, s)197 (solvent:CD.sub.3 OD:CDCl.sub.3 =1:4) 1.22(3H, td, J=7.6, 0.9Hz), 2.65(2H, q, J=7.6Hz), 2.98(1H, dd, J=17.2, 5.0Hz), 3.11 (1H, dd, J=17.5, 5.0Hz), 4.99(1H, dt, J=4.3, 8.6Hz), 5.18 (2H, s), 6.47(1H, s), 7.51(1H, dd, J=7.6, 8.3Hz), 7.63(1H, d, J=8.3Hz), 7.81(1H, d, J=7.6Hz), 7.92(1H, s), 2.59(3H, s), 7.51(1H, s)198 (solvent:CD.sub.3 OD:CDCl.sub.3 =1:4) 1.22(3H, t, J=7.4Hz), 2.58 (3H, s), 2.64(2H, q, J=7.4Hz), 3.97(1H, dd, J=11.6, 3.5Hz), 4.10(1H, dd, J=11.2, 3.9Hz), 4.67(1H, t, J=3.6Hz), 5.17(1H, s), 6.46(1H, s), 7.50(1H, s), 7.51(1H, dd, J=7.6, 7.6Hz), 7.62(1H, d, J=7.6Hz), 7.85(1H, d, J=7.6Hz)______________________________________
TABLE 134______________________________________Ex.No. Structural formula______________________________________199 ##STR643##200 ##STR644##201 ##STR645##202 ##STR646##203 ##STR647##______________________________________
TABLE 135______________________________________.sup.1 H-NMR .delta. ppm______________________________________199 (solvent:CD.sub.3 OD/CDCl.sub.3 (1/4)) 0.99(3H, t, J=7.6Hz), 1.5- 1.7(2H, m), 2.60(3H, s), 2.70(2H, t, J=7.8Hz), 3.0-3.3(2H, m), 5.1-5.2(1H, m), 5.27(2H, s), 6.76(2H, d, J=8.9Hz), 7.53 (2H, d, J=8.9Hz), 7.64(1H, d, J=7.9Hz), 7.90(1H, dd, J= 7.9, 7.6Hz), 8.11(1H, d, J=7.6Hz)200 (solvent:CD.sub.3 OD/CDCl.sub.3 (1/4)) 0.98(3H, t, J=7.3Hz), 1.5- 1.7(2H, m), 2.57(3H, s), 2.75(2H, t, J=7.6Hz), 3.0-3.3(2H, m), 3.75(3H, s), 5.1-5.2(1H, m), 5.31(2H, s), 6.50(1H, d, J= 8.9Hz), 7.60(1H, d, J=8.9Hz), 7.67(1H, d, J=7.6Hz), 7.92(1H, dd, J=7.6, 7.3Hz), 8.14(1H, d, J=7.3Hz)201 (solvent:CD.sub.3 OD/CDCl.sub.3 (1/4)) 1.01(3H, t, J=7.3Hz), 1.63(3H, d, J=7.3Hz), 1.5-1.7(2H, m), 2.62(3H, s), 2.74(2H, t, J=7.6Hz), 3.78(3H, s), 4.80(1H, t, J=7.3Hz), 5.29(2H, s), 6.73(1H, d, J=8.9Hz), 7.55(1H, d, J=8.9Hz), 7.66(1H, d, J=7.6Hz), 7.93(1H, dd, J=7.6, 7.6Hz), 8.15(1H, d, J=7.6Hz)202 (solvent:CD.sub.3 OD/CDCl.sub.3 (1/4)) 1.23(3H, t, J=7.4Hz), 1.62(3H, d, J=7.3Hz), 2.58(3H, s), 2.69(2H, q, J=7.4Hz), 3.87(3H, s), 4.82(1H, q, J=7.3, 7.3Hz), 5.31(2H, s), 6.49(1H, s), 7.71(1H, d, J=7.9Hz), 7.71(1H, s), 7.94(1H, dd, J=7.6, 7.9Hz), 8.16(1H, d, J=7.6Hz)203 (solvent:CD.sub.3 OD/CDCl.sub.3 (1/4)) 1.24(3H, t, J=7.6Hz), 1.7- 2.2(4H, m), 2.57(3H, s), 2.6-2.8(1H, m), 2.67(2H, q, J= 7.6Hz), 3.0-3.3(2H, m), 3.8-4.0(1H, m), 4.4-4.6(1H, m), 5.25 (2H, s), 6.44(1H, s), 7.47(1H, s), 7.54(1H, d, J=7.6Hz), 7.57 (1H, d, J=7.0Hz), 7.85(1H, dd, J=7.6, 7.9Hz)______________________________________
TABLE 136______________________________________Ex.No. Structural formula______________________________________204 ##STR648##205 ##STR649##206 ##STR650##207 ##STR651##208 ##STR652##______________________________________
TABLE 137______________________________________.sup.1 H-NMR .delta. ppm______________________________________204 (solvent:CD.sub.3 OD/CDCl.sub.3 (1/4)) 1.25(3H, t, J=7.4Hz), 1.5- 2.3(5H, m), 2.57(3H, s), 2.67(2H, q, J=7.4Hz), 2.7-2.9(1H, m), 3.1-4.8(4H, m), 5.25(2H, s), 6.44(1H, s), 7.47(1H, s), 7.5- 7.7(2H, m), 7.85(1H, dd, J=7.6, 7.9Hz)205 (solvent:CD.sub.3 OD/CDCl.sub.3 (1/4)) 1.24(3H, t, J=7.6Hz), 1.43(3H, d, J=6.6Hz), 2.58(3H, s), 2.67(2H, q, J=7.4Hz), 2.74(2H, dd, J=5.6, 3.0Hz), 4.5-4.6(1H, m), 5.25(2H, s), 6.51(1H, s), 7.48(1H, s), 7.61(1H, d, J=7.9Hz), 7.89(1H, dd, J=7.6, 7.9Hz), 8.14(1H, d, J=7.6Hz)206 (solvent:CD.sub.3 OD/CDCl.sub.3 (1/4)) 1.2-1.3(6H, m), 2.57(1H, s), 2.67(2H, q, J=7.5Hz), 2.8-3.0(2H, m), 3.4-3.8(4H, m), 5.24 (2H, s), 6.4-6.5(1H, m), 7.48(1H, s), 7.5-7.7(2H, m), 7.85(1H, dd, J=7.6, 7.9Hz),207 (solvent:CD.sub.3 OD/CDCl.sub.3 (1/9)) 1.25(3H, t, J=7.4Hz), 1.29(3H, d, J=6.3Hz), 2.58(3H, s), 2.69(2H, q, J=7.4Hz), 4.4-4.6(1H, m), 4.7-4.9(1H, m), 5.30(2H, s), 6.50(1H, s), 7.50(1H, s), 7.66(1H, d, J=7.6Hz), 7.93(1H, dd, J=7.6, 7.6Hz), 8.13(1H, d, J=7.6Hz)208 (solvent:CD.sub.3 OD/CDCl.sub.3 (1/9)) 1.23(1.2H, t, J=7.6Hz), 1.26(1.8H, t, J=7.6Hz), 2.1-2.6(2H, m), 2.59(3H, s), 2.8-3.0(2H, m), 3.8-4.8(3H, m), 5.3-5.4(3H, m), 6.44(0.6H, s), 6.48(0.4H, s), 7.5-8.1(3H, s),______________________________________
TABLE 138__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________209 ##STR653##210 ##STR654##211 ##STR655##212 ##STR656##213 ##STR657##__________________________________________________________________________
TABLE 139______________________________________.sup.1 H-NMR .delta. ppm______________________________________209 (solvent:CDCl.sub.3 /MeOD(9/1)) 1.26(3H, t, J=7.4Hz), 1.9- 2.1(1H, m), 2.2-2.4(1H, m), 2.59(3H, s), 2.70(1H, q, J= 7.4Hz), 3.6-3.9(1H, m), 4.84(1H, dt, J=4.3, 4.6Hz), 5.30(2H, s), 6.49(1H, s), 7.53(1H, s), 7.69(1H, d, J=7.6Hz), 7.96(1H, dd, J=7.6, 7.6Hz), 8.11(1H, d, J=7.6Hz)210 (solvent:DMSO-d.sub.6) 1.19(3H, t, J=7.6Hz), 2.57(3H, s), 2.63(2H, q, J=7.6Hz), 3.78(2H, s), 4.02(2H, s), 5.36(2H, s), 6.56(1H, s), 7.67(1H, s), 7.71(1H, d, J=7.3Hz), 8.03(1H, dd, J=6.6, 5.9Hz), 8.09(1H, d, J=6.6Hz),211 (solvent:CDCl.sub.3 /MeOD(4/1)) 1.26(3H, t, J=7.6Hz), 1.29(3H, t, J=7.3Hz), 2.59(3H, s), 2.69(2H, q, J=7.5Hz), 3.68(2H, s), 4.05(2H, s), 4.20(2H, q, J=7.3Hz), 5.29(2H, s), 6.46(1H, s), 7.52(1H, s), 7.67(1H, d, J=7.9Hz), 7.95(1H, dd, J=7.6, 7.9Hz), 8.11(1H, d, J=7.6Hz)212 (solvent:DMSO-d.sub.6) 1.25(3H, t, J=7.6Hz), 2.58(3H, s), 2.68(2H, q, J=7.6Hz), 3.50(1H, m), 3.78(1H, m), 4.74(1H, m), 5.30(2H, s), 5.46(1H, d, J=2.0Hz), 6.49(1H, s), 6.69(1H, m), 6.85(1H, d, J=7.9Hz), 6.91(1H, s), 7.13(1H, t, J= 7.9Hz), 7.56(1H, s), 7.67(1H, d, J=7.6Hz), 7.98(1H, t, J= 7.6Hz), 8.08(1H, d, J=7.6Hz), 8.51(1H, m), 9.08(1H, s), 12.61(1H, s)213 (solvent:DMSO-d.sub.6) 1.19(3H, t, J=7.6Hz), 2.58(3H, s), 2.64(2H, q, J=7.6Hz), 3.85(2H, m), 4.55(1H, m), 5.34(1H, br), 5.39(2H, s), 6.60(1H, s), 7.68(1H, s), 7.74(1H, d, J= 7.6Hz), 8.05(1H, t, J=7.6Hz), 8.12(1H, d, J=7.6Hz), 8.63 (1H, d, J=8.3Hz), 12.55(1H, s), 12.90(1H, br)______________________________________
TABLE 140__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________214 ##STR658##215 ##STR659##216 ##STR660##217 ##STR661##218 ##STR662##__________________________________________________________________________
TABLE 141______________________________________.sup.1 H-NMR .delta. ppm______________________________________214 (solvent:CDCl.sub.3) 1.25(3H, t, J=7.6Hz), 2.58(3H, s), 2.68(2H, q, J=7.6Hz), 3.85(3H, s), 4.11(2H, m), 4.88(1H, m), 5.29(2H, s), 6.52(1H, s), 7.49(1H, s), 7.65(1H, d, J= 8.3Hz), 7.91(1H, t, J=8.3Hz), 8.15(1H, d, J=8.3Hz), 8.80 (1H, d, J=8.3Hz) 12.69(1H, s)215 (solvent:DMSO-d.sub.6) 1.18(3H, t, J=7.3Hz), 2.51(3H, s), 2.63(2H, q, J=7.3Hz), 3.79(1H, dd, J=11.2Hz, 3.9Hz), 3.91(1H, dd, J=11.2Hz, 3.9Hz), 4.55(1H, m), 5.48(2H, s), 6.68(1H, s), 7.70(1H, s), 8.58(1H, d, J=7.9Hz), 9.05(1H, s), 9.21(1H, s), 12.57(1H, s)216 (solvent:CDCl.sub.3) 1.27(3H, t, J=7.3Hz), 2.59(3H, br), 2.89(3H, s), 2.68(2H, q, J=7.3Hz), 3.85(3H, s), 4.06(1H, dd, J=11.2Hz, 3.6Hz), 4.18(1H, dd, J=11.2Hz, 3.6Hz), 4.90(1H, m), 5.34(2H, s), 6.52(1H, s), 7.51(1H, s), 8.58(1H, m), 9.00(1H, s), 9.37(1H, s), 12.71(1H, s),217 (solvent:CDCl.sub.3) 1.27(3H, t, J=7.6Hz), 2.60(3H, s), 2.71(2H, q, J=7.6Hz), 3.79(2H, s), 3.85-4.10(4H, m), 4.64-4.80(2H, m), 5.33(2H, s), 6.49(1H, s), 7.57(1H, s), 7.72(1H, d, J=7.6Hz), 8.00(1H, t, J=7.6Hz), 8.10(1H, d, J= 7.6Hz)218 (solvent:CDCl.sub.3) 1.25(3H, t, J=7.6Hz), 2.57(3H, s), 2.67(2H, q, J=7.6Hz), 3.2-3.7(2H, m), 3.70(s, 1.2H), 3.81(s, 1.8H), 4.0-4.3(2H, m), 4.37(0.6H, m), 4.90(0.4H, m), 5.24 (2H, s), 6.44(1H, s), 7.48(1H, s), 7.5-7.9(3H, m), 12.63(1H,______________________________________ s)
TABLE 142__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________219 ##STR663##220 ##STR664##221 ##STR665##222 ##STR666##223 ##STR667##__________________________________________________________________________
TABLE 143______________________________________.sup.1 H-NMR .delta. ppm______________________________________219 (solvent:CDCl.sub.3) 1.00(3H, t, J=7.6Hz), 1.24(3H, t, J= 7.6Hz), 1.81(2H, q, J=7.6Hz), 2.58(3H, s), 2.67(2H, q, J= 7.6Hz), 3.72(2H, m), 3.94-4.06(4H, m), 5.27(2H, s), 6.56(1H, s), 7.48(1H, s), 7.63(1H, d, J=7.6Hz), 7.93(1H, t, J=7.6Hz), 8.15(1H, d, J=7.6Hz), 8.52(1H, brs), 12.73(1H, s),220 (solvent:CDCl.sub.3) 1.24(3H, t, J=7.3Hz), 1.38(3H, s), 2.58(3H, s), 2.67(2H, q, J=7.3Hz), 3.7-4.1(6H, m), 5.27(2H, s), 6.56 (1H, s), 7.48(1H, s), 7.64(1H, d, J=7.6Hz), 7.92(1H, t, J= 7.6Hz), 8.14(1H, d, J=7.6Hz), 8.49(1H, s), 12.73(1H, s)221 (solvent:CDCl.sub.3) 1.22(3H, t, J=7.6Hz), 2.57(3H, s), 2.65(2H, q, J=7.6Hz), 3.83(8H, s), 5.29(2H, s), 6.66(1H, s), 7.46(1H, s), 7.65(1H, d, J=6.6Hz), 7.93(1H, t, J=7.6Hz), 8.14(1H, d, J=7.9Hz), 9.12(1H, s), 12.82(1H, s)222 (solvent:CDCl.sub.3) 1.26(3H, t, J=7.6Hz), 2.58(3H, s), 2.67-2.72(2H, m), 3.75-3.82(2H, m), 3.83-3.95(2H, m), 4.14-4.20(1H, m), 4.20-4.26(2H, m), 5.27(2H, s), 6.45(1H, s), 7.50(1H, s), 7.62(1H, d, J=6.9Hz), 7.92(1H, t, J=6.9Hz), 8.13(1H, d, J=6.9Hz), 8.53(1H, d, J=7.9Hz), 12.66(1H, s)223 (solvent:DMSO-d.sub.6) 1.21(3H, t, J=7.6Hz), 2.58(3H, s), 2.65(2H, q, J=7.6Hz), 3.7-3.9(4H, m), 4.61(1H, m), 5.05(1H, br), 5.37(2H, s), 6.58(1H, s), 7.65(1H, s), 7.71(1H, dd, J= 6.8Hz, 2.1Hz), 8.02-8.25(2H, m), 8.39(1H, t, J=5.8Hz), 8.62 (1H, d, J=8.3Hz), 12.54(1H, s),______________________________________
TABLE 144__________________________________________________________________________Ex. No. Structural formula__________________________________________________________________________224 ##STR668##225 ##STR669##226 ##STR670##__________________________________________________________________________
TABLE 145______________________________________.sup.1 H-NMR .delta. ppm______________________________________224 (solvent:DMSO-d.sub.6) 1.21(3H, t, J=7.6Hz), 2.57(3H, s), 2.64(2H, q, J=7.6Hz), 3.54(1H, m), 3.72(1H, m), 4.19(1H, m), 5.34(2H, s), 5.59(1H, br), 6.55(1H, s), 7.63(1H, s), 7.69(1H, dd, J=6.1Hz, 2.8Hz), 8.05(2H, m), 8.51(1H, t, J= 6.1Hz), 12.55(1H, s), 12.65(1H, br)225 (solvent:CDCl.sub.3) 1.25(3H, t, J=7.6Hz), 1.26(3H, t, J= 7.3Hz), 2.58(3H, s), 2.68(2H, q, J=7.6Hz), 3.10(1H, dd, J= 8.9Hz, 5.6Hz), 3.80-3.88(1H, m), 4.06(2H, d, J=5.6Hz), 4.20 (2H, qJ=7.3Hz), 4.25, 4.35(1H, m), 4.70(1H, m), 5.28(2H, s), 6.45(1H, s), 7.15(1H, br), 7.49(1H, s), 7.63(1H, d, J= 6.9Hz), 7.92(1H, t, J=6.9Hz), 8.15(1H, d, J=6.9Hz), 8.85 (1H, d, J=7.6Hz), 12.66(1H, s)226 (solvent:CDCl.sub.3) 1.25(3H, t, J=7.6Hz), 2.58(3H, s), 2.68(2H, q, J=7.6Hz), 3.57(1H, d, J=5.3Hz), 3.83(3H, s), 3.88(2H, m), 4.44(1H, m), 5.25(2H, s), 6.47(1H, s), 7.49(1H, s), 7.63(1H, d, J=7.6Hz), 7.91(1H, t, J=7.6Hz), 8.14(1H, d, J=7.6Hz), 8.36(1H, br), 12.68(1H, s)______________________________________

Number	Name	Date	Kind
4663332	Carson et al.	May 1987
4672066	Carson et al.	Jun 1987

Number	Date	Country
276065	Jul 1988	EPX
64-29363	Jan 1989	JPX

Pyridine compounds which are useful as leukotriene B4 antagonist

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