Patent Grant
8263599
The present invention relates to a STAT3/5 activation inhibitor.
A protein family of STAT (signal transducers and activators of transcription) is one of a DNA binding protein and plays a role in information transmission and transcription activation. At present, the STAT family is known to have 6 different members (STAT 1, STAT 2, STAT 3, STAT 4, STAT 5 and STAT 6) and several iso-forms (STAT 1α, STAT 1β, STAT 3α, STAT3β, STAT 5a and STAT 5b). The activity of STAT is regulated by stimulation of various cytokines and mitogen. When a cytokine binds to its receptors, Janus protein tyrosine kinase (JAK) associated with the receptors is activated.
STAT 3 has a SH2 (src homology 2) domain capable of recognizing the structure of a specifically phosphorylated tyrosine. It is considered that STAT 3 specifically recognizes the phosphorylated tyrosine within a gp130 cell region and is conveyed onto gp 130 and tyrosine is phosphorylated by JAK. STAT 3 having phosphorylated tyrosine forms a STAT 3 dimer (homodimer) via its SH2 domain or a dimer (heterodimer) of STAT 3 and STAT1, which moves into a nucleus, and recognizes a specific DNA sequence and binds it. In this way, STAT3 is known to regulate transcription of many genes.
Such in-vivo roles of STAT3/5 are reported in several documents.
For example, Non-Patent Document 1 describes the relationships between activation of STAT 3 and IL-6-signaling pathways and between IL-6 and chronic diseases such as Alzheimer's disease, rheumatism, Crohn disease and anemia and cancer associated disease such as cachexia.
Furthermore, Non-Patent Document 2 describes the relationship between STAT 3 activation and Hepatitis C Virus, Non-Patent Document 3 describes the relationship between STAT 3 activation and psoriasis, individually. Moreover, Non-Patent Document 2 sets forth the relationships between STAT 3 and an inflammatory disease and an autoimmune disease, and Non-Patent Document 4 sets forth the relationships between STAT 3 activation and obesity, diabetes, infertility, and thermal dysregulaton, etc., individually. Non-Patent Documents 5 and 6, etc. describe that STATS is a critical factor in IgE-induced MC (mast cell) activation, and inflammatory and autoimmune diseases, and describe STATS's roles in allergies, inflammations, hyperprolactinemia, and malignant tumors.
On the other hand, it is known that an aromatic compound having a collagen production inhibitory action is present (Patent Document 1). However, it has been not yet known that the aromatic compound described in Patent Document 1 has a STATS/5 activation inhibitory action.
An object of the present invention is to provide a STAT3/5 activation inhibitor.
The present inventors repeatedly studied on an aromatic compound described in Patent Document 1. As a result, they found that the compound has a STAT3/5 activation inhibitory action. The present invention has been attained based on such a finding.
Therefore, the present invention provides STAT3/5 activation inhibitors represented by the following items A to C.
(i) when X1 represents a group —CH═, then R3 represents a hydrogen atom;
(ii) when X1 represents a group —CH═, 1 represents 1, T represents —CO—, and R14 represents a hydrogen atom or an alkyl group that may have a hydroxyl group as a substituent, R15 represents the group (24);
(iii) when X1 represents a group —CH═, 1 represents 1, and T represents —N(R17)—B3—CO—, R14 and R15, together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 10-membered saturated or unsaturated heterocyclic ring, wherein, on the heterocyclic ring, 1 to 3 groups of (28) are present as a substituent(s);
(iv) when X1 represents a nitrogen atom, and l represents 0, or when X1 represents a nitrogen atom, l represents 1, and T represents —CO— or —SO2, R15 is not a group (5), (7), (19), or (20); and
(v) when R6 represents a cycloalkyl group that may have on the cycloalkyl ring, a substituent selected from the group consisting of an amino-substituted lower alkyl group that may have a lower alkyl group and a lower alkyl group that may have a halogen atom as a substituent, R4 represents a group -(T)1-N(R14)R15 (wherein T and l are the same as described above, and R14 and R15, together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 10-membered saturated heterocyclic ring; or R14 and R15 form a group
Item B: The STAT3 activation inhibitor according to item A for preventing or treating a symptom or disease associated with activation of STAT3.
Item C: The STAT3 activation inhibitor according to item B, in which the symptom or disease associated with activation of STAT3 is autoimmune disease, diabetes, infection, central disease, cancer-associated disease or psoriasis.
The present invention further provides a method for preventing or treating a symptom or disease associated with activation of STAT3 by administering, to a patient, an effective dose of an aromatic compound (1) or a salt thereof according to item A.
The present invention further provides use of a compound (1) or a salt thereof according to item A for producing the STAT3/5 activation inhibitor.
The aromatic compound (1) or a salt thereof serving as an active ingredient of the STAT3/5 activation inhibitor of the present invention is an aromatic compound (1) or a salt thereof represented by item 1 below and preferably aromatic compounds or salts thereof represented by items 2 to 48.
Item 1: An aromatic compound or a salt thereof represented by the general formula:
wherein X1 represents a nitrogen atom or a group —CH═,
However, that the aforementioned compound or a salt thereof satisfies the following requirements (i) to (v):
(i) when X1 represents a group —CH═, then R3 represents a hydrogen atom;
(ii) when X1 represents a group —CH═, 1 represents 1, T represents —CO—, and R14 represents a hydrogen atom or an alkyl group that may have a hydroxyl group as a substituent, R15 represents the group (24);
(iii) when X1 represents a group —CH═, l represents 1, and T represents —N(R17)—B3—CO—, R14 and R15, together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 10-membered saturated or unsaturated heterocyclic ring, wherein, on the heterocyclic ring, 1 to 3 groups of (28) are present as a substituent(s);
(iv) when X1 represents a nitrogen atom, and l represents 0, or when X1 represents a nitrogen atom, l represents 1, and T represents —CO— or —SO2, R15 is not a group (5), (7), (19), or (20); and
(v) when R6 represents a cycloalkyl group that may have on the cycloalkyl ring, a substituent selected from the group consisting of an amino-substituted lower alkyl group that may have a lower alkyl group and a lower alkyl group that may have a halogen atom as a substituent, R4 represents a group -(T)l-N(R14)R15 (wherein T and l are the same as described above, and R14 and R15, together with the nitrogen atom to which they bind, may bind to each other, directly or via a nitrogen atom, oxygen atom, or sulfur atom to form a 5- to 10-membered saturated heterocyclic ring; or R14 and R15 form a group
Item 2: The aromatic compound or a salt thereof according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-1) to (1-7) below or a salt thereof as an active ingredient:
wherein Y3 represents a lower alkylene group.
Item 3: The aromatic compound or a salt thereof according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-8) to (1-14) below or a salt thereof as an active ingredient:
wherein Y3 represents a lower alkylene group.
Item 4: The aromatic compound or a salt thereof according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-15) to (1-21) below or a salt thereof as an active ingredient:
wherein Y3 represents a lower alkylene group.
Item 5: The aromatic compound or a salt thereof according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-22) to (1-28) below or a salt thereof as an active ingredient:
wherein Y3 represents a lower alkylene group.
Item 6: The aromatic compound or a salt thereof according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-29) to (1-35) below or a salt thereof as an active ingredient:
wherein Y3 represents a lower alkylene group.
Item 7: The aromatic compound or a salt thereof according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-36) to (1-42) below or a salt thereof as an active ingredient:
wherein Y3 represents a lower alkylene group.
Item 8: The aromatic compound or a salt thereof according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-43) to (1-49) below or a salt thereof as an active ingredient:
wherein Y3 represents a lower alkylene group.
Item 9: The aromatic compound or a salt thereof according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-50) to (1-56) below or a salt thereof as an active ingredient:
wherein Y3 represents a lower alkylene group.
Item 10: The aromatic compound or a salt thereof according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-57) to (1-63) below or a salt thereof as an active ingredient:
wherein Y3 represents a lower alkylene group.
Item 11: The aromatic compound or a salt thereof according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-64) to (1-70) below or a salt thereof as an active ingredient:
wherein Y3 represents a lower alkylene group, and Z1 represents a lower alkenylene group.
Item 12: The aromatic compound or a salt thereof according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-71) to (1-77) below or a salt thereof as an active ingredient:
wherein Y3 represents a lower alkylene group.
Item 13: The aromatic compound or a salt thereof according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-78) to (1-84) below or a salt thereof as an active ingredient:
wherein Y3 represents a lower alkylene group.
Item 14: The aromatic compound or a salt thereof according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-85) to (1-91) below or a salt thereof as an active ingredient:
wherein Y3 represents a lower alkylene group.
Item 15: The aromatic compound or a salt thereof according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-92) to (1-98) below or a salt thereof as an active ingredient:
wherein Y3 represents a lower alkylene group.
Item 16: The aromatic compound or a salt thereof according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-99) to (1-105) below or a salt thereof as an active ingredient:
wherein Y3 represents a lower alkylene group.
Item 17: The aromatic compound or a salt thereof according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-106) to (1-112) below or a salt thereof as an active ingredient:
wherein Y3 represents a lower alkylene group.
Item 18: The aromatic compound or a salt thereof according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-113) to (1-119) below or a salt thereof as an active ingredient:
wherein Y3 represents a lower alkylene group.
Item 19: The aromatic compound or a salt thereof according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-120) to (1-126) below or a salt thereof as an active ingredient:
wherein Y3 represents a lower alkylene group, and Z2 represents a lower alkynylene group.
Item 20: The aromatic compound or a salt thereof according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-127) to (1-133) below or a salt thereof as an active ingredient:
wherein Y3 represents a lower alkylene group.
Item 21: The aromatic compound or a salt thereof according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-134) to (1-140) below or a salt thereof as an active ingredient:
wherein Y3 represents a lower alkylene group, and Z3 represents a lower alkylene group or a group —N(R8d)—.
Item 22: The aromatic compound or a salt thereof according to any one of items 1 to 21, wherein Y is a group —O—.
Item 23: The aromatic compound or a salt thereof according to any one of items 1 to 21, wherein Y is a group —N(R5)—.
Item 24: The aromatic compound or a salt thereof according to any one of items 1 to 21, wherein Y is a group —CO—, a group —CH(OH)—, a lower alkylene group, a group —S(O)n-, or a group —C(═N—OH)—.
Item 25: The aromatic compound or a salt thereof according to any one of items 1 to 21, wherein A is a group
Item 26: The aromatic compound or a salt thereof according to any one of items 1 to 21, wherein A is a group
Item 27: The aromatic compound or a salt thereof according to any one of items 1 to 21, wherein R4 represents an imidazolyl lower alkyl group, a 1,2,4-triazolyl lower alkyl group, a 1,2,3-triazolyl lower alkyl group, a 1,2,5-triazolyl lower alkyl group, a pyrazolyl lower alkyl group, a pyrimidinyl lower alkyl group that may have an oxo group as a substituent on the pyrimidine ring, a 3,5-dioxoisoxazolidin-4-ylidene lower alkyl group, a 1,2,4-oxadiazolyl lower alkyl group that may have a lower alkyl group as a substituent on the 1,2,4-oxadiazole ring, a thiazolidinyl lower alkyl group that may have an oxo group as a substituent on the thiazolidine ring, a group
or a group
Item 28: The aromatic compound or a salt thereof according to any one of items 1 to 21, represented by the general formula (1) wherein R4 represents a group -(T)1-N(R14)R15 (T, R14, and R15 are the same as defined above) and l represents 0.
Item 29: The aromatic compound or a salt thereof according to any one of items 1 to 21, wherein R4 is a group -(T)1-N(R14)R15, and l is 1.
Item 30: The aromatic compound or a salt thereof according to any one of items 1 to 21, wherein R4 is a group -(T)1-N(R14)R15, l is 1, and T is a group —N(R17)—B3—CO—.
Item 31: The aromatic compound or a salt thereof according to any one of items 1 to 21, wherein R4 is a group -(T)1-N(R14)R15, l is 1, and T is a group —B19—N(R18)—CO—.
Item 32: The aromatic compound or a salt thereof according to any one of items 1 to 21, wherein R4 is a group -(T)1-N(R14)R15, l is 1, and T is a group —B4—CO—.
Item 33: The aromatic compound or a salt thereof according to any one of items 1 to 21, wherein R4 is a group -(T)1-N(R14)R15, l is 1, and T is a group -Q-B5—CO—.
Item 34: The aromatic compound or a salt thereof according to any one of items 1 to 21, wherein R4 is a group -(T)1-N(R14)R15, l is 1, and T is a group —B6—N (R19)—B7—.
Item 35: The aromatic compound or a salt thereof according to any one of items 1 to 21, wherein R4 is a group -(T)1-N(R14)R15, l is 1, and T is a group —CO—B8—.
Item 36: The aromatic compound or a salt thereof according to any one of Items 1 to 21, wherein R4 is a group -(T)1-N(R14)R15, l is 1, and T is a group —CH(OH)—B9—.
Item 37: The aromatic compound or a salt thereof according to any one of items 1 to 21, wherein R4 is a group -(T)1-N(R14)R15, l is 1, and T is a group —CO—B10—CO—.
Item 38: The aromatic compound or a salt thereof according to any one of items 1 to 21, wherein R4 is a group -(T)1-N(R14)R15, l is 1, and T is a group —CH(OH)—B11—CO—.
Item 39: The aromatic compound or a salt thereof according to any one of items 1 to 21, wherein R4 is a group -(T)1-N(R14)R15, l is 1, and T is a group —CO—.
Item 40: The aromatic compound or a salt thereof according to any one of items 1 to 21, wherein R4 is a group -(T)1-N(R14)R15, l is 1, and T is a group —SO2—.
Item 41: The aromatic compound or a salt thereof according to any one of items 1 to 21, wherein R4 is a group -(T)1-N(R14)R15, l is 1, and T is a group —B23a—CO—CO—.
Item 42: The aromatic compound or a salt thereof according to any one of items 1 to 21, wherein R4 is a group -(T)1-N(R14)R15, l is 1, and T is a lower alkylene group.
Item 43: The aromatic compound or a salt thereof according to item 1, comprising a compound selected from the group consisting of the compounds represented by the general formulas (1-1), (1-2), (1-8), (1-9), (1-15), (1-16), (1-29), (1-30), (1-43), (1-44), (1-57), (1-58), (1-64) and (1-65) or a salt thereof as an active ingredient, wherein Y is a group —O-or a group —N(R5)—, A is a group
and
Item 44: The aromatic compound or a salt thereof according to item 43, wherein l is 1, and T is a group —N(R17)—B3—CO—.
Item 45: The aromatic compound or a salt thereof according to item 43, wherein l is 1, and T is a group —B4—CO—.
Item 46: The aromatic compound or a salt thereof according to item 43, wherein l is 1, and T is a group —CO—.
Item 47: The aromatic compound or a salt thereof according to item 43, wherein l is 0.
Item 48: The aromatic compound or a salt thereof according to item 1, comprising a compound selected from the group consisting of N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]ethylamino}-2-methoxyphenoxy)pyridin-3-yl]-3,4-dichlorobenzamide, N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]ethylamino}phenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide, N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]ethylamino}-2-fluorophenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide, N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-fluorophenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide, N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methoxyphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide, N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]ethylamino}-2-methoxyphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide, N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]ethylamino}-2-methylphenoxy)pyridin-3-yl]-3,4-dichlorobenzamide, N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methylphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide, N-(6-{4-[3-(4-piperonylpiperazin-1-yl)-3-oxopropyl]phenoxy}pyridin-3-yl)-3,4-dichlorobenzenesulfonamide, N-[6-(4-{4-[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]piperazin-1-yl}phenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide, N-[6-(4-{4-[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}phenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide, N-{6-[(4-{4-[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}phenyl)methylamino]pyridin-3-yl}-4-trifluoromethylbenzamide, N-[6-(4-{4-[2-(4-benzylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}-2-methylphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide, N-[6-(4-{4-[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}-2-methylphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide, N-[6-(4-{4-[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}-2-methylphenoxy)pyridin-3-yl]-3,4-dichlorobenzamide, N-{6-[4-(4-benzylpiperazine-1-carbonyl)phenoxy]pyridin-3-yl}-4-trifluoromethylbenzamide, N-{6-[4-(4-benzylpiperazine-1-carbonyl)phenoxy]pyridin-3-yl}-3,4-dichlorobenzamide, N-[6-({4-[3-(4-piperonylpiperazin-1-yl)-3-oxopropyl]phenyl}methylamino)pyridin-3-yl]-4-trifluoromethylbenzamide, N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]ethylamino}-2-fluorophenoxy)pyridin-3-yl]-3,4-dichlorobenzamide, N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-fluorophenoxy)pyridin-3-yl]-3,4-dichlorobenzamide, N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methoxyphenoxy)pyridin-3-yl]-3,4-dichlorobenzamide, N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}phenoxy)pyridin-3-yl]-3,4-dichlorobenzamide, 1-(6-{4-[3-(4-piperonylpiperazin-1-yl)-3-oxopropyl]phenoxy}pyridin-3-yl)-3-(3,4-dichlorophenyl)-1-ethylurea, N-(6-{4-[3-(4-piperonylpiperazin-1-yl)-3-oxopropyl]phenoxy}pyridin-3-yl)-4-trifluoromethylbenzamide, N-[6-(4-{[2-(4-benzylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methylphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide, N-[6-(4-{4-[2-(4-benzylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}phenoxy)pyridin-3-yl]-3,4-dichlorobenzamide, N-(6-{4-[3-(4-piperonylpiperazine-1-carbonyl)piperidin-1-yl]phenoxy}pyridin-3-yl)-3,4-dichlorobenzamide, N-[6-(4-{4-[2-(4-benzylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}phenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide, N-{6-[(4-{4-[2-(4-benzylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}phenyl)methylamino]pyridin-3-yl}-4-trifluoromethylbenzamide, N-(6-{4-[(2-{4-[4-(4-fluorobenzoyl)phenyl]piperazin-1-yl}-2-oxoethyl)methylamino]-2-methoxyphenoxy}pyridin-3-yl)-4-trifluoromethylbenzamide, 2-(4-piperonylpiperazin-1-yl)-N-{3-methyl-4-[5-(4-trifluoromethylphenoxymethyl)pyridin-2-yloxy]phenyl}-2-oxoacetamide, N-[6-(4-{[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]methylamino}-2-methylphenoxy)pyridin-3-yl]-2-fluoro-4-trifluoromethylbenzamide, N-[6-(4-{4-[2-(4-piperonylpiperazin-1-yl)-2-oxoethyl]piperidin-1-yl}-2-methoxyphenoxy)pyridin-3-yl]-4-trifluoromethylbenzamide and 4-(3-{3-methyl-4-[5-(4-trifluoromethylbenzoylamino)pyridin-2-yloxy]phenyl}-2-oxohexahydropyrimidin-1-yl)benzoic acid ethyl ester, or a salt thereof as an active ingredient.
The aromatic compound or a salt thereof serving as the active ingredient of the present invention is a known compound and described in Patent Document 1.
Specific examples of individual groups shown in the general formula (1) are as follows.
Examples of the lower alkenylene group include linear or branched alkenylene groups having 2 to 6 carbon atoms and 1 to 3 double bonds such as vinylene, 1-propenylene, 1-methyl-1-propenylene, 2-methyl-1-propenylene, 2-propenylene, 2-butenylene, 1-butenylene, 3-butenylene, 2-pentenylene, 1-pentenylene, 3-pentenylene, 4-pentenylene, 1,3-butadienylene, 1,3-pentadienylene, 2-penten-4-ynylene, 2-hexenylene, 1-hexenylene, 5-hexenylene, 3-hexenylene, 4-hexenylene, 3,3-dimethyl-1-propenylene, 2-ethyl-1-propenylene, 1,3,5-hexatrienylene, 1,3-hexadienylene, and 1,4-hexadienylene groups.
Examples of the lower alkynylene group include linear or branched alkynylene groups having 2 to 6 carbon atoms and 1 to 3 triple bonds such as ethynylene, 1-propynylene, 1-methyl-1-propynylene, 2-methyl-1-propynylene, 2-propynylene, 2-butynylene, 1-butynylene, 3-butynylene, 2-pentynylene, 1-pentynylene, 3-pentynylene, 4-pentynylene, 2-pentyn-4-ynylene, 2-hexynylene, 1-hexynylene, 5-hexynylene, 3-hexynylene, 4-hexynylene, 3,3-diethyl-1-propynylene, and 2-ethyl-1-propynylene groups.
Examples of the lower alkoxy group include linear or branched alkoxy groups having 1 to 6 carbon atoms such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxyl, pentyloxy, and hexyloxy groups.
Examples of the lower alkyl group include linear or branched alkyl groups having 1 to 6 carbon atoms such as methyl, ethyl, propyl, isopropyl, 2,2-dimethylpropyl, 1-ethylpropyl, butyl, isobutyl, tert-butyl, isopentyl, pentyl, and hexyl groups.
Examples of the lower alkyl group which may have a lower alkoxy group as a substituent include, in addition to the above described lower alkyl groups, linear or branched alkyl groups having 1 to 6 carbon atoms which may have a linear or branched alkoxy group having 1 to 6 carbon atoms as a substituent such as methoxymethyl, 1-ethoxyethyl, 2-methoxyethyl, 2-propoxyethyl, 3-isopropoxypropyl, 4-butoxybutyl, 5-pentyloxypentyl, 6-hexyloxyhexyl, 1,1-dimethyl-2-methoxyethyl, 2-methyl-3-ethoxypropyl, and 3-methoxypropyl groups.
Examples of the lower alkanoyl group include linear or branched alkanoyl groups having 1 to 6 carbon atoms such as formyl, acetyl, propionyl, butyryl, isobutyryl, pentanoyl, tert-butylcarbonyl, and hexanoyl groups.
Examples of the phenyl lower alkyl group include phenylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as benzyl, 2-phenylethyl, 1-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 5-phenylpentyl, 6-phenylhexyl, 1,1-dimethyl-2-phenylethyl, and 2-methyl-3-phenylpropyl groups.
Examples of the lower alkylene group include linear or branched alkylene groups having 1 to 6 carbon atoms such as methylene, ethylene, trimethylene, 2-methyltrimethylene, 2,2-dimethylethylene, 2,2-dimethyltrimethylene, 1-methyltrimethylene, methylmethylene, ethylmethylene, tetramethylene, pentamethylene, and hexamethylene groups.
Examples of the lower alkenylene group which may have a phenyl group as a substituent include linear or branched alkenylene groups, which have 2 to 6 carbon atoms and 1 to 3 double bonds, and which may have a phenyl group as a substituent such as vinylene, 1-propenylene, 1-methyl-1-propenylene, 2-methyl-1-propenylene, 2-propenylene, 2-butenylene, 1-butenylene, 3-butenylene, 2-pentenylene, 1-pentenylene, 3-pentenylene, 4-pentenylene, 1,3-butadienylene, 1,3-pentadienylene, 2-pentene-4-ynylene, 2-hexenylene, 1-hexenylene, 5-hexenylene, 3-hexenylene, 4-hexenylene, 3,3-dimethyl-1-propenylene, 2-ethyl-1-propenylene, 1,3,5-hexatrienylene, 1,3-hexadienylene, 1,4-hexadienylene, 1-phenylvinylene, 3-phenyl-1-propenylene, 3-phenyl-1-methyl-1-propenylene, 3-phenyl-2-methyl-1-propenylene, 1-phenyl-2-propenylene, 1-phenyl-2-butenylene, 3-phenyl-1-butenylene, 1-phenyl-3-butenylene, 5-phenyl-2-pentenylene, 4-phenyl-1-pentenylene, 2-phenyl-3-pentenylene, 1-phenyl-4-pentenylene, 1-phenyl-1,3-butadienylene, 1-phenyl-1,3-pentadienylene, 1-phenyl-2-penten-4-ynylene, 1-phenyl-2-hexenylene, 3-phenyl-1-hexenylene, 4-phenyl-5-hexenylene, 6-phenyl-3-hexenylene, 5-phenyl-4-hexenylene, 1-phenyl-3,3-dimethyl-1-propenylene, 1-phenyl-2-ethyl-1-propenylene, 6-phenyl-1,3,5-hexatrienylene, 1-phenyl-1,3-hexadienylene, and 2-phenyl-1,4-hexadienylene groups.
Examples of the lower alkylene group which may be substituted with a group selected from the group consisting of a lower alkoxy group and a phenyl group include, in addition to the above described lower alkylene groups, linear or branched alkylene groups having 1 to 6 carbon atoms which may be substituted with 1 or 2 groups selected from the group consisting of a linear or branched alkoxy group having 1 to 6 carbon atoms and a phenyl group such as methoxymethylene, 2-phenylethylene, 3-ethyoxytrimethylene, 1-propoxy-2-methyltrimethylene, 1-phenyl-2,2-dimethylethylene, 3-phenyl-2,2-dimethyltrimethylene, 2-butoxy-1-methyltrimethylene, phenylmethylmethylene, 2-pentyloxyethylmethylene, 4-phenyl-2-hexyloxytetramethylene, 3-phenylpentamethylene, 5-phenylhexamethylene, ethoxymethylene, 1-phenylethylene, 3-phenyltrimethylene, and 2-phenyl-1-methoxyethylene groups.
Examples of the 5- to 15-membered monocyclic, bicyclic or tricyclic saturated or unsaturated heterocyclic group which has 1 to 4 nitrogen atoms, oxygen atoms or sulfur atoms include pyrrolidinyl, piperidinyl, piperazinyl, morpholino, pyridyl, 1,2,5,6-tetrahydropyridyl, 1,2,4-triazolyl, 1,2,3-triazolyl, 1,2,5-triazolyl, thiazolidinyl, 1,2,3,4-tetrazolyl, thienyl, quinolyl, 1,4-dihydroquinolyl, benzothiazolyl, pyrazyl, pyrimidyl, pyridazyl, 2H-pyrrolyl, pyrrolyl, 1,3,4-oxadiazolyl, tetrahydropyranyl, tetrahydrofuryl, furazanyl, carbostyryl, 3,4-dihydrocarbostyryl, 1,2,3,4-tetrahydroquinolyl, 1,2,3,4-tetrahydroisoquinolyl, indolyl, isoindolyl, indolinyl, benzoimidazolyl, benzooxazolyl, imidazolidinyl, isoquinolyl, quinazolidinyl, quinoxalinyl, cinnolinyl, phthalazinyl, carbazoyl, acridinyl, chromanyl, isoindolinyl, isochromanyl, pyrazolyl, imidazolyl, pyrazolidinyl, phenothiazinyl, benzofuryl, 2,3-dihydrobenzo[b]furyl, benzothienyl, phenoxathiinyl, phenoxazinyl, 4H-chromenyl, 1H-indazolyl, phenazinyl, xanthenyl, thianthrenyl, 2-imidazolinyl, 2-pyrrolinyl, furyl, oxazolyl, isooxazolyl, isooxazolidinyl, thiazolyl, isothiazolyl, pyranyl, 2-thiazolinyl, 2-pyrazolinyl, quinuclidinyl, 1,4-benzooxadinyl, 3,4-dihydro-2H-1,4-benzooxadinyl, 3,4-dihydro-2H-1,4-benzothiazinyl, 1,4-benzothiazinyl, 1,2,3,4-tetrahydroquinoxalinyl, 1,3-dithia-2,4-dihydronaphthalenyl, phenanthridinyl, 1,4-dithianaphthalenyl, dibenz[b,e]azepine, and 6,11-dihydro-5H-dibenz[b,e]azepine groups.
Examples of the halogen atom include a fluorine atom, chlorine atom, bromine atom and iodine atom.
Examples of the lower alkoxy group which may have a halogen atom as a substituent include linear or branched alkoxy groups having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, pentyloxy, hexyloxy, trifluoromethoxy, trichloromethoxy, chloromethoxy, bromomethoxy, fluoromethoxy, iodomethoxy, difluoromethoxy, dibromomethoxy, 2-chloroethoxy, 2,2,2-trifluoroethoxy, 2,2,2-trichloroethoxy, 3-chloropropoxy, 2,3-dichloropropoxy, 4,4,4-trichlorobutoxy, 4-fluorobutoxy, 5-chloropentyloxy, 3-chloro-2-methylpropoxy, 6-bromohexyloxy, and 5,6-dichlorohexyloxy groups.
Examples of the lower alkyl group which may have a halogen atom as a substituent include, in addition to the above described lower alkyl groups, linear or branched alkyl groups having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents such as trifluoromethyl, trichloromethyl, chloromethyl, bromomethyl, fluoromethyl, iodomethyl, difluoromethyl, dibromomethyl, dichloromethyl, 2-chloroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 3-chloropropyl, 2,3-dichloropropyl, 4,4,4-trichlorobutyl, 4-fluorobutyl, 5-chloropentyl, 3-chloro-2-methylpropyl, 5-bromohexyl, and 5,6-dibromohexyl groups.
Examples of the lower alkylsulfonyl group include linear or branched alkylsulfonyl groups having 1 to 6 carbon atoms such as methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, tert-butylsulfonyl, pentylsulfonyl, and hexylsulfonyl groups.
Examples of the phenyl group which may be substituted, on the phenyl ring, with a lower alkyl group which may have a halogen atom include phenyl groups which may be substituted, on the phenyl ring, with 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms such as phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-butylphenyl, 4-pentylphenyl, 4-hexyiphenyl, 3,4-dimethylphenyl, 3,4-diethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4,5-trimethylphenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2-(bromomethyl)phenyl, 3-(2-chloroethyl)phenyl, 4-(2,3-dichloropropyl)phenyl, 4-(4-fluorobutyl)phenyl, 3-(5-chloropentyl)phenyl, 4-(5-bromohexyl)phenyl, 4-(5,6-dibromohexyl)phenyl, 3,4-di(trifluoromethyl)phenyl, 3,4-di(4,4,4-trichlorobutyl)phenyl, 2,4-di(3-chloro-2-methylpropyl)phenyl, 2,5-di(3-chloropropyl)phenyl, 2,6-di(2,2,2-trifluoroethyl)phenyl, 3,4,5-tri(trifluoromethyl)phenyl, 4-(2,2,2-trichloroethyl)phenyl, 2-methyl-4-trifluoromethylphenyl, and 3-ethyl-4-trichloromethyl groups.
Examples of the lower alkylthio group include linear or branched alkylthio groups having 1 to 6 carbon atoms such as methylthio, ethylthio, propylthio, isopropylthio, butylthio, tert-butylthio, pentylthio, and hexylthio groups.
Examples of the amino group which may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group as a substituent include amino groups which may have 1 or 2 groups selected from the group consisting of linear or branched alkyl groups having 1 to 6 carbon atoms and linear or branched alkanoyl groups having 1 to 6 carbon atoms as substituents such as amino, methylamino, ethylamino, propylamino, isopropylamino, butylamino, tert-butylamino, pentylamino, hexylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino, N-methyl-N-ethylamino, N-ethyl-N-propylamino, N-methyl-N-butylamino, N-methyl-N-hexylamino, N-acetylamino, N-formylamino, N-propionylamino, N-butyrylamino, N-isobutyrylamino, N-pentanoylamino, N-tert-butylcarbonylamino, N-hexanoylamino, diacetylamino, N-acetyl-N-methylamino, and N-acetyl-N-ethylamino groups.
Examples of the naphthyl group which may be substituted on the naphthalene ring with 1 to 3 substituents selected from the group consisting of a lower alkyl group, a halogen atom, and an amino group which may have a group selected from the group consisting of a lower alkyl group and a lower alkanoyl group include naphthyl groups which may have, on the naphthalene ring, 1 to 3 substituents selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms, a halogen atom, and an amino group which may have 1 or 2 substituents selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms and a linear or branched alkanoyl group having 1 to 6 carbon atoms such as (1-or 2-)naphthyl, 1-methyl-(2-, 3-, 4-, 5-, 6-, 7- or 8-)naphthyl, 2-ethyl-(1-, 3-, 4-, 5-, 6-, 7- or 8-)naphthyl, 3-n-propyl-(1-, 2-, 4-, 5-, 6-, 7- or 8-)naphthyl, 4-n-butyl-(1-, 2-, 3-, 5-, 6-, 7- or 8-)naphthyl, 4-methyl-(1-, 2-, 3-, 5-, 6-, 7- or 8-)naphthyl, 5-n-pentyl-(1-, 2-, 3-, 4-, 6-, 7- or 8-)naphthyl, 6-n-hexyl-(1-, 2-, 3-, 4-, 5-, 7- or 8-)naphthyl, 1,7-dimethyl-(2-, 3-, 4-, 5-, 6- or 8-)naphthyl, 1,2,8-trimethyl-(3-, 4-, 5-, 6- or 7-)naphthyl, 1-dimethylamino-(2-, 3-, 4-, 5-, 6-, 7- or 8-)naphthyl, 2-dimethylamino-(1-, 3-, 4-, 5-, 6-, 7- or 8-)naphthyl, 3-methylamino-(1-, 2-, 4-, 5-, 6-, 7- or 8-)naphthyl, 5-amino-(1-, 2-, 3-, 4-, 6-, 7- or 8-)naphthyl, 5-dimethylamino-(1-, 2-, 3-, 4-, 6-, 7- or 8-)naphthyl, 4-(N-methyl-N-ethylamino)-(1-, 2-, 3-, 5-, 6-, 7- or 8-)naphthyl, 1-methyl-2-dimethylamino-(3-, 4-, 5-, 6-, 7- or 8-)naphthyl, 1-chloro-(2-, 3-, 4-, 5-, 6-, 7- or 8-)naphthyl, and 1-acetylamino-(2-, 3-, 4-, 5-, 6-, 7- or 8-)naphthyl groups.
Examples of the alkyl group which may have a lower alkoxy group as a substituent include, in addition to the above described lower alkyl groups which may have a lower alkoxy group as a substituent, linear or branched alkyl groups having 1 to 8 carbon atoms which may have a linear or branched alkoxy group having 1 to 6 carbon atoms as a substituent such as heptyl, 1-ethylpentyl, octyl, 7-methoxyheptyl, 1-ethoxyheptyl, 2-propoxyl-1-ethylpentyl, 3-isopropoxyoctyl, 7-butoxyheptyl, 8-pentyloxyoctyl, and 5-hexyloxy-1-ethylpentyl groups.
Examples of the amino substituted lower alkyl group which may have a lower alkyl group include linear or branched alkyl groups having 1 to 6 carbon atoms substituted with an amino group which may have 1 or 2 linear or branched alkyl groups having 1 to 6 carbon atoms such as aminomethyl, 2-aminoethyl, 1-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl, 1,1-dimethyl-2-aminoethyl, 2-methyl-3-aminopropyl, methylaminomethyl, 1-ethylaminoethyl, 2-propylaminoethyl, 3-isopropylaminopropyl, 4-butylaminobutyl, 5-pentylaminopentyl, 6-hexylaminohexyl, dimethylaminomethyl, 2-diethylaminoethyl, 2-diisopropylaminoethyl, (N-ethyl-N-propylamino)methyl, and 2-(N-methyl-N-hexylamino)ethyl groups.
Examples of the cycloalkyl group include cycloalkyl groups having 3 to 16 carbon atoms such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl, cyclotridecyl, cycloteradecyl, cyclopentadecyl, and cyclohexadecyl groups.
Examples of the cycloalkyl group which may be substituted with a group selected from the group consisting of an amino substituted lower alkyl group which may have a lower alkyl group and a lower alkyl group which may have a halogen atom as a substituent on the cycloalkyl ring include, in addition to the above described cycloalkyl groups, cycloalkyl groups having 3 to 16 carbon atoms which may be substituted, on the cycloalkyl ring, with 1 to 3 groups selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms substituted with an amino group which may have 1 or 2 linear or branched alkyl groups having 1 to 6 carbon atoms and a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents such as 4-dimethylaminomethylcyclohexyl, 2-(aminomethyl)cyclopropyl, 3-(2-aminomethyl)cyclobutyl, 2-(1-aminoethyl)cyclopentyl, 3-(3-aminopropyl)cyclohexyl, 3-(4-aminobutyl)cycloheptyl, 4-(5-aminopentyl)cyclooctyl, 4-(6-aminohexyl)cyclohexyl, 2-(1,1-dimethyl-2-aminoethyl)cycloheptyl, 3-(2-methyl-3-aminopropyl)cyclopentyl, 3-(methylaminomethyl)cyclohexyl, 2-(1-ethylaminoethyl)cyclooctyl, 2-(2-propylaminoethyl)cyclohexyl, 3-(3-isopropylaminopropyl)cyclopentyl, 4-(4-butylaminobutyl)cycloheptyl, 2-(5-pentylaminopentyl)cyclohexyl, 2-(6-hexylaminohexyl)cyclopentyl, 3-(dimethylaminomethyl)cyclohexyl, 3-[(N-ethyl-N-propylamino)methyl]cycloheptyl, 4-[2-(N-methyl-N-hexylamino)ethyl]cyclooctyl, 4-dimethylaminomethylcyclononyl, 2-(aminomethyl)cyclodecyl, 3-(2-aminomethyl)cycloundecyl, 2-(1-aminoethyl)cyclododecyl, 3-(3-aminopropyl)cyclotridecyl, 3-(4-aminobutyl)cyclotetradecyl, 4-(5-aminopentyl)cyclopentadecyl, 4-(6-aminohexyl)cyclohexadecyl, 2-(1,1-dimethyl-2-aminoethyl)cyclononyl, 3-(2-methyl-3-aminopropyl)cyclodecyl, 3-(methylaminomethyl)cycloundecyl, 2-(1-ethylaminoethyl)cyclododecyl, 2-(2-propylaminoethyl)cyclotridecyl, 3-(3-isopropylaminopropyl)cyclotetradecyl, 4-(4-butylaminobutyl)cyclopentadecyl, 2-(5-pentylaminopentyl)cyclohexadecyl, 2-(6-hexylaminohexyl)cyclononyl, 3-(dimethylaminomethyl)cyclododecyl, 3-[(N-ethyl-N-propylamino)methyl]cyclodecyl, 4-[2-(N-methyl-N-hexylamino)ethyl]cyclohexadecyl, 2,2-dimethylcyclopropyl, and 2-trifluoromethylcyclopropyl groups.
Examples of the lower alkenyl group include linear or branched alkenyl groups having 2 to 6 carbon atoms and 1 to 3 double bonds such as vinyl, 1-propenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 2-propenyl, 2-butenyl, 1-butenyl, 3-butenyl, 2-pentenyl, 1-pentenyl, 3-pentenyl, 4-pentenyl, 1,3-butadienyl, 1,3-pentadienyl, 2-penten-4-ynyl, 2-hexenyl, 1-hexenyl, 5-hexenyl, 3-hexenyl, 4-hexenyl, 3,3-dimethyl-1-propenyl, 2-ethyl-1-propenyl, 1,3,5-hexatrienyl, 1,3-hexadienyl, and 1,4-hexadienyl groups.
Examples of the lower alkenyl group which may have a halogen atom as a substituent include, in addition to the above described lower alkenyl groups, linear or branched alkenyl groups having 2 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents and which have 1 to 3 double bonds such as 3,3,3-trifluoro-1-propenyl, 2-bromovinyl, 3-chloro-1-propenyl, 3-iodo-1-methyl-1-propenyl, 3-fluoro-2-methyl-1-propenyl, 2-butenyl, 4,4,3-trichloro-1-butenyl, 4,4-difluoro-3-butenyl, 5-fluoro-2-pentenyl, 5,5,3-tribromo-1-pentenyl, 5-chloro-3-pentenyl, 5,5,5-trifluoro-4-pentenyl, 4-chloro-1,3-butadienyl, 5-fluoro-1,3-pentadienyl, 5-bromo-2-penten-4-ynyl, 6-fluoro-2-hexenyl, 6,6,5-trifluoro-1-hexenyl, 6-chloro-5-hexenyl, 5-bromo-3-hexenyl, 6-chloro-4-hexenyl, 3,3-dimethyl-2-chloro-1-propenyl, 3-fluoro-2-ethyl-1-propenyl, 6-chloro-1,3,5-hexatrienyl, 6-bromo-1,3-hexadienyl, and 6-fluoro-1,4-hexadienyl groups.
Examples of the benzoyl group (which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group which may have a halogen atom as a substituent and a halogen atom) include benzoyl groups (which may have, on the phenyl ring, with 1 to 3 substituents selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms and which may have 1 to 3 halogen atoms as substituents and a halogen atom) such as benzoyl, 3,4-difluorobenzoyl, 2-fluorobenzoyl, 3-bromobenzoyl, 4-iodobenzoyl, 4-methylbenzoyl, 2-methylbenzoyl, 3-methylbenzoyl, 2-ethylbenzoyl, 3-ethylbenzoyl, 4-ethylbenzoyl, 4-isopropylbenzoyl, 3-butylbenzoyl, 4-pentylbenzoyl, 4-hexylbenzoyl, 3,4-dimethylbenzoyl, 3,4-diethylbenzoyl, 2,4-dimethylbenzoyl, 2,5-dimethylbenzoyl, 2,6-dimethylbenzoyl, 3,4,5-trimethylbenzoyl, 2-trifluoromethylbenzoyl, 3-trifluoromethylbenzoyl, 4-trifluoromethylbenzoyl, 2-(bromomethyl)benzoyl, 3-(2-chloroethyl)benzoyl, 4-(2,3-dichloropropyl)benzoyl, 4-(4-fluorobutyl)benzoyl, 3-(5-chloropentyl)benzoyl, 4-(5-bromohexyl)benzoyl, 4-(5,6-dibromohexyl)benzoyl, 3,4-di(trifluoromethyl)benzoyl, 3,4-di(4,4,4-trichlorobutyl)benzoyl, 2,4-di(3-chloro-2-methylpropyl)benzoyl, 2,5-di(3-chloropropyl)benzoyl, 2,6-di(2,2,2-trifluoroethyl)benzoyl, 3,4,5-tri(trifluoromethyl)benzoyl, 4-(2,2,2-trichloroethyl)benzoyl, 2-methyl-4-trifluoromethylbenzoyl, 3-ethyl-4-trichloromethylbenzoyl, 2-chloro-4-trifluoromethylbenzoyl, 3-ethyl-4-fluorobenzoyl, 3-fluoro-4-trichloromethylbenzoyl, 2-methyl-3-trifluoromethyl-4-trifluoromethylbenzoyl, 3-fluorobenzoyl, 4-fluorobenzoyl, 2-bromobenzoyl, 4-bromobenzoyl, 2-iodobenzoyl, 3-iodobenzoyl, 2,3-dibromobenzoyl, 2,4-diiodobenzoyl, 2,5-difluorobenzoyl, 2,6-dichlorobenzoyl, 2,4,6-trichlorobenzoyl, 2,4-difluorobenzoyl, 3,5-difluorobenzoyl, 2,6-difluorobenzoyl, 2-chlorobenzoyl, 3-chlorobenzoyl, 4-chlorobenzoyl, 2,3-dichlorobenzoyl, 2,4-dichlorobenzoyl, 2,5-dichlorobenzoyl, 3,4-dichlorobenzoyl, 2,6-dichlorobenzoyl, 3,5-dichlorobenzoyl, 2,4,6-trifluorobenzoyl, and 2,4-difluorobenzoyl groups.
Examples of the halogen substituted lower alkyl group include linear or branched alkyl groups having 1 to 6 carbon atoms which have 1 to 3 halogen atoms as substituents such as trifluoromethyl, trichloromethyl, chloromethyl, bromomethyl, fluoromethyl, iodomethyl, difluoromethyl, dibromomethyl, 2-chloroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 3-chioropropyl, 2,3-dichloropropyl, 4,4,4-trichlorobutyl, 4-fluorobutyl, 5-chloropentyl, 3-chloro-2-methylpropyl, 5-bromohexyl, and 5,6-dibromohexyl groups.
Examples of the lower alkylenedioxy group include linear or branched alkylene groups having 1 to 4 carbon atoms such as methylenedioxy, ethylenedioxy, trimethylenedioxy, and tetramethylenedioxy groups.
Examples of the amino group which may have a substituent selected from the group consisting of a lower alkyl group, a lower alkanoyl group, a benzoyl group and a cycloalkyl group include amino groups which may have 1 or 2 substituents selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkanoyl group having 1 to 6 carbon atoms, a benzoyl group, and a cycloalkyl group having 3 to 16 carbon atoms such as amino, methylamino, ethylamino, propylamino, isopropylamino, butylamino, tert-butylamino, pentylamino, hexylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, dipentylamino, dihexylamino, N-methyl-N-ethylamino, N-ethyl-N-propylamino, N-methyl-N-butylamino, N-methyl-N-hexylamino, N-methyl-N-acetylamino, N-acetylamino, N-formylamino, N-propionylamino, N-butyrylamino, N-isobutyrylamino, N-pentanoylamino, N-tert-butylcarbonylamino, N-hexanoylamino, N-ethyl-N-acetylamino, N-benzoylamino, N-ethyl-N-benzoylamino, N-methyl-N-benzoylamino, N-acetyl-N-benzoylamino, cyclopropylamino, cyclobutylamino, cyclopentylamino, cyclohexylamino, cycloheptylamino, cyclooctylamino, N-methyl-N-cyclohexylamino, N-methyl-N-cyclopentylamino, N-methyl-N-cycloheptylamino, N-cyclohexyl-N-acetylamino, N-cyclopentyl-N-benzoylamino, cyclononylamino, cyclodecylamino, cyclododecylamino, cyclotridecylamino, cyclotetradecylamino, cyclopentadecylamino, N-methyl-N-cyclohexadecylamino, N-methyl-N-cyclononylamino, N-methyl-N-cyclodecylamino, N-cycloundecyl-N-acetylamino, and N-cyclohexadecyl-N-benzoyl groups.
Examples of the lower alkanoyl group which may have a halogen atom as a substituent include, in addition to the above described lower alkanoyl groups, linear or branched alkanoyl groups having 2 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents such as 2,2,2-trifluoroacetyl, 2,2,2-trichloroacetyl, 2-chloroacetyl, 2-bromoacetyl, 2-fluoroacetyl, 2-iodoacetyl, 2,2-difluoroacetyl, 2,2-dibromoacetyl, 3,3,3-trifluoropropionyl, 3,3,3-trichloropropionyl, 3-chloropropionyl, 2,3-dichloropropionyl, 4,4,4-trichlorobutyryl, 4-fluorobutyryl, 5-chloropentanoyl, 3-chloro-2-methylpropionyl, 6-bromohexanoyl, and 5,6-dibromohexanoyl groups.
Examples of the lower alkoxycarbonyl group include alkoxycarbonyl groups whose alkoxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl, and hexyloxycarbonyl groups.
Examples of the lower alkanoyloxy group include linear or branched alkanoyloxy groups having 2 to 6 carbon atoms such as acetyloxy, propionyloxy, butyryloxy, isobutyryloxy, pentanoyloxy, tert-butylcarbonyloxy, and hexanoyloxy groups.
Examples of the 5- or 6-membered saturated or unsaturated heterocyclic group having 1 to 4 nitrogen atoms, oxygen atoms or sulfur atoms include pyrrolidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, pyridyl, 1,2,5,6-tetrahydropyridyl, thienyl, pyrazyl, pyrimidyl, pyridazyl, pyrrolyl, 2H-pyrrolyl, imidazolidinyl, pyrazolyl, imidazolyl, pyrazolidinyl, furazanyl, 2-imidazolinyl, imidazolidinyl, 2-pyrrolinyl, furyl, oxazolyl, isooxazolidinyl, isooxazolyl, thiazolyl, isothiazolyl, pyranyl, 2-pyrazolidinyl, 1,2,4-triazolyl, 1,2,3-triazolyl, 1,2,5-triazolyl, thiazolidinyl, 2-thiazolinyl, 1,2,3,4-tetrazolyl, 1,3,4-oxadiazolyl, tetrahydropyranyl, and tetrahydrofuryl groups.
Examples of the 5-to 7-membered saturated heterocyclic ring formed by binding R11 and R12 each other, together with nitrogen atoms bound to them, through or not through a nitrogen atom, a sulfur atom or an oxygen atom, include pyrrolidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, and homopiperazinyl groups.
Examples of the imidazolyl lower alkyl group include imidazolylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1, 2, 4 or 5-)imidazolylmethyl, 2-[(1, 2, 4 or 5-)imidazolyl]ethyl, 1-[(1, 2, 4 or 5-)imidazolyl]ethyl, 3-[(1, 2, 4 or 5-)imidazolyl]propyl, 4-[(1, 2, 4 or 5-)imidazolyl]butyl, 5-[(1, 2, 4 or 5-)imidazolyl]pentyl, 6-[(1, 2, 4 or 5-)imidazolyl]hexyl, 1,1-dimethyl-2-[(1, 2, 4 or 5-)imidazolyl]ethyl, and 2-methyl-3-[(1, 2, 4 or 5-)imidazolyl]propyl groups.
Examples of the 1,2,4-triazolyl lower alkyl group include 1,2,4-triazolylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1, 3 or 5-)1,2,4-triazolylmethyl, 2-[(1, 3 or 5-)1,2,4-triazolyl]ethyl, 1-[(1, 3 or 5-)1,2,4-triazolyl]ethyl, 3-[(1, 3 or 5-)1,2,4-triazolyl]propyl, 4-[(1, 3 or 5-)1,2,4-triazolyl]butyl, 5-[(1, 3 or 5-)1,2,4-triazolyl]pentyl, 6-[(1, 3 or 5-)1,2,4-triazolyl]hexyl, 1,1-dimethyl-2-[(1, 3 or 5-)1,2,4-triazolyl]ethyl, and 2-methyl-3-[(1, 3 or 5-)1,2,4-triazolyl]propyl groups.
Examples of the 1,2,3-triazolyl lower alkyl group include 1,2,3-triazolylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1, 4 or 5-)1,2,3-triazolylmethyl, 2-[(1, 4 or 5-)1,2,3-triazolyl]ethyl, 1-[(1, 4 or 5-)1,2,3-triazolyl]ethyl, 3-[(1, 4 or 5-)1,2,3-triazolyl]propyl, 4-[(1, 4 or 5-)1,2,3-triazolyl]butyl, 5-[(1, 4 or 5-)1,2,3-triazolyl]pentyl, 6-[(1, 4 or 5-)1,2,3-triazolyl]hexyl, 1,1-dimethyl-2-[(1, 4 or 5-)1,2,3-triazolyl]ethyl, and 2-methyl-3-[(1, 4 or 5-)1,2,3-triazolyl]propyl groups.
Examples of the 1,2,5-triazolyl lower alkyl group include 1,2,5-triazolylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1, 3 or 4-)1,2,5-triazolylmethyl, 2-[(1, 3 or 4-)1,2,5-triazolyl]ethyl, 1-[(1, 3 or 4-)1,2,5-triazolyl]ethyl, 3-[(1, 3 or 4-)1,2,5-triazolyl]propyl, 4-[(1, 3 or 4-)1,2,5-triazolyl]butyl, 5-[(1, 3 or 4-)1,2,5-triazolyl]pentyl, 6-[(1, 3 or 4-)1,2,5-triazolyl]hexyl, 1,1-dimethyl-2-[(1, 3 or 4-)1,2,5-triazolyl]ethyl, and 2-methyl-3-[(1, 3 or 4-)1,2,5-triazolyl]propyl groups.
Examples of the pyrazolyl lower alkyl group include pyrazolylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1, 3, 4 or 5-)pyrazolylmethyl, 2-[(1, 3, 4 or 5-)pyrazolyl]ethyl, 1-[(1, 3, 4 or 5-)pyrazolyl]ethyl, 3-[(1, 3, 4 or 5-)pyrazolyl]propyl, 4-[(1, 3, 4 or 5-)pyrazolyl]butyl, 5-[(1, 3, 4 or 5-)pyrazolyl]pentyl, 6-[(1, 3, 4 or 5-)pyrazolyl]hexyl, 1,1-dimethyl-2-[(1, 3, 4 or 5-)pyrazolyl]ethyl, and 2-methyl-3-[(1, 3, 4 or 5-)pyrazolyl]propyl groups.
Examples of the pyrimidinyl lower alkyl group which may have an oxo group as a substituent on the pyrimidine ring include pyrimidinylalkyl groups which may have 1 to 3 oxo groups as substituents on the pyrimidine ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2, 4, 5 or 6-)pyrimidinylmethyl, 2-[(2, 4, 5 or 6-)pyrimidinyl]ethyl, 1-[(2, 4, 5 or 6-)pyrimidinyl]ethyl, 3-[(2, 4, 5 or 6-)pyrimidinyl]propyl, 4-[(2, 4, 5 or 6-)pyrimidinyl]butyl, 5-[(2, 4, 5 or 6-)pyrimidinyl]pentyl, 6-[(2, 4, 5 or 6-)pyrimidinyl]hexyl, 1,1-dimethyl-2-[(2, 4, 5 or 6-)pyrimidinyl]ethyl, 2-methyl-3-[(2, 4, 5 or 6-)pyrimidinyl]propyl, [(1, 3, 4 or 5-)2,6-dioxopryrimidinyl]methyl, [(1, 3, 4, 5 or 6-)2-oxopyrimidinyl]methyl, [(1, 2, 4 or 5-)6-oxopyrimidinyl]methyl, [(1, 2, 5 or 6-)4-oxopyrimidinyl]methyl, [(1, 3, 5 or 6-)2,4-dioxopyrimidinyl]methyl, 2-[(4 or 6-)2,5-dioxopyrimidinyl]ethyl, 1-[(1, 3, 4 or 5-)2,6-dioxopyrimidinyl]ethyl, 3-[(1, 3 or 5-)2,4,6-trioxopyrimidinyl]propyl, 4-[(1, 3, 4 or 5-)2,6-dioxopyrimidinyl]butyl, 5-[(4 or 6-)2,5-dioxopyrimidinyl]pentyl, 6-[(1, 3, 5 or 6-)2,4-dioxopyrimidinyl]hexyl, 1,1-dimethyl-[(1, 3, 4 or 5-)2,6-dioxopyrimidinyl]ethyl, and 2-methyl-3-[(1, 3, 4 or 5-)2,6-dioxopyrimidinyl]propyl groups.
Examples of the 3,5-dioxoisoxazolidin-4-ylidene lower alkyl group include 3,5-dioxoisoxazolidin-4-ylidenealkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as 3,5-dioxoisoxazolidin-4-ylidenemethyl, 3,5-dioxoisoxazolidin-4-ylideneethyl, 3,5-dioxoisoxazolidin-4-ylidenepropyl, 3,5-dioxoisoxazolidin-4-ylideneisopropyl, 3,5-dioxoisoxazolidin-4-ylidenebutyl, 3,5-dioxoisoxazolidin-4-ylidenepentyl, and 3,5-dioxoisoxazolidin-4-ylidenehexyl groups.
Examples of the 1,2,4-oxadiazolyl lower alkyl group which may have a lower alkyl group as a substituent on the 1,2,4-oxadiazol ring include 1,2,4-oxadiazolylalkyl groups which may have a linear or branched alkyl group having 1 to 6 carbon atoms as a substituent on the 1,2,4-oxadiazol ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (3 or 5-)1,2,4-oxadiazolylmethyl, 2-[(3 or 5-)1,2,4-oxadiazolyl]ethyl, 1-[(3 or 5-)1,2,4-oxadiazolyl]ethyl, 3-[(3 or 5-)1,2,4-oxadiazolyl]propyl, 4-[(3 or 5-)1,2,4-oxadiazolyl]butyl, 5-[(3 or 5-)1,2,4-oxadiazolyl]pentyl, 6-[(3 or 5-)1,2,4-oxadiazolyl]hexyl, 1,1-dimethyl-2-[(3 or 5-)1,2,4-oxadiazolyl]ethyl, 2-methyl-3-[(3 or 5-)1,2,4-oxadiazolyl]propyl, 5-methyl-3-(1,2,4-oxadiazolyl)methyl, 3-ethyl-2-[5-(1,2,4-oxadiazolyl)]ethyl, 1-[3-propyl-5-(1,2,4-oxadiazolyl)]ethyl, 3-[5-butyl-3-(1,2,4-oxadiazolyl)]propyl, 4-[3-pentyl-5-(1,2,4-oxadiazolyl)]butyl, 5-[5-hexyl-3-(1,2,4-oxadiazolyl)]pentyl, 6-[3-methyl-5-(1,2,4-oxadiazolyl)]hexyl, 1,1-dimethyl-2-[5-isopropyl-3-(1,2,4-oxadiazolyl)]ethyl, and 2-methyl-3-[3-isobutyl-5-(1,2,4-oxadiazolyl)]propyl groups.
Examples of the thiazolydinyl lower alkyl group which may have an oxo group as a substituent on the thiazolydine ring include thiazolydinylalkyl groups which may have 1 to 3 oxo groups as substituents on the thiazolydine ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2, 3, 4 or 5-)thiazolidinylmethyl, 2-[(2, 3, 4 or 5-)thiazolidinyl]ethyl, 1-[(2, 3, 4 or 5-)thiazolidinyl]ethyl, 3-[(2, 3, 4 or 5-)thiazolidinyl]propyl, 4-[(2, 3, 4 or 5-)thiazolidinyl]butyl, 5-[(2, 3, 4 or 5-)thiazolidinyl]pentyl, 6-[(2, 3, 4 or 5-)thiazolidinyl]hexyl, 1,1-dimethyl-2-[(2, 3, 4 or 5-)thiazolidinyl]ethyl, 2-methyl-3-[(2, 3, 4 or 5-)thiazolidinyl]propyl, 2,4-dioxo-5-thiazolidinylmethyl, 2-[2-oxo-(3, 4 or 5-)thiazolidinyl]ethyl, 1-[4-oxo-(2, 3 or 5-)thiazolidinyl]ethyl, 3-[5-oxo-(2, 3 or 4-)thiazolidinyl]propyl, 4-[2,5-dioxo-(3 or 4-)thiazolidinyl]butyl, 5-[2,4,5-trioxo-3-thiazolidinyl]pentyl, 6-[4,5-dioxo-(2 or 3-)thiazolidinyl]hexyl, 1,1-dimethyl-2-[2,4-dioxo-(3 or 5-)thiazolidinyl]ethyl, 2-methyl-3-[2,4-dioxo-(3 or 5-)thiazolidinyl]propyl, and 3-[2,4-dioxo-(3 or 5-)thiazolidinyl]propyl groups.
Examples of the phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring include, in addition to the above described phenyl lower alkyl groups, phenylalkyl groups which may have a linear or branched alkylenedioxy group having 1 to 4 carbon atoms as a substituent on the phenyl ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as 3,4-methylenedioxybenzyl, 3,4-trimethylenedioxybenzyl, 2-(2,3-ethylenedioxyphenyl)ethyl, 1-(3,4-trimethylenedioxyphenyl)ethyl, 3-(2,3-tetramethylenedioxyphenyl)propyl, 4-(3,4-methylenedioxyphenyl)butyl, 5-(2,3-ethylenedioxyphenyl)pentyl, 6-(3,4-trimethylenedioxyphenyl)hexyl, 1,1-dimethyl-2-(2,3-methylenedioxyphenyflethyl, and 2-methyl-3-(3,4-ethylenedioxyphenyl)propyl groups.
Examples of the lower alkoxycarbonyl lower alkyl group include alkoxycarbonylalkyl groups whose alkoxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as methoxycarbonylmethyl, ethoxycarbonylmethyl, 2-methoxycarbonylethyl, 2-ethoxycarbonylethyl, 1-ethoxycarbonylethyl, 3-methoxycarbonylpropyl, 3-ethoxycarbonylpropyl, 4-ethoxycarbonylbutyl, 5-isopropoxycarbonylpentyl, 6-propoxycarbonylhexyl, 1,1-dimethyl-2-butoxycarbonylethyl, 2-methyl-3-tert-butoxycarbonylpropyl, 2-pentyloxycarbonylethyl, and hexyloxycarbonylmethyl groups.
Examples of the carboxy lower alkyl group include carboxyalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as carboxymethyl, 2-carboxyethyl, 1-carboxyethyl, 3-carboxypropyl, 4-carboxybutyl, 5-carboxypentyl, 6-carboxyhexyl, 1,1-dimethyl-2-carboxyethyl, and 2-methyl-3-carboxypropyl groups.
Examples of the morpholino substituted lower alkanoyl group include morpholino substituted alkanoyl groups whose alkanoyl moiety is a linear or branched alkanoyl group having 2 to 6 carbon atoms such as 2-[(2, 3 or 4-)morpholino]acetyl group, 3-[(2, 3 or 4-)morpholino]propionyl, 2-[(2, 3 or 4-)morpholino]propionyl, 4-[(2, 3 or 4-)morpholino]butyryl, 5-[(2, 3 or 4-)morpholino]pentanoyl, 6-[(2, 3 or 4-)morpholino]hexanoyl, 2,2-dimethyl-2-[(2, 3 or 4-)morpholino]propionyl, and 2-methyl-3-[(2, 3 or 4-)morpholino]propionyl groups.
Examples of the piperazinylcarbonyl lower alkyl group which may be substituted on the piperazine ring with a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring include piperazinylcarbonylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms and which may be substituted on the piperazine ring with 1 to 3 phenylalkyl groups which may have a linear or branched alkylenedioxy group having 1 to 4 carbon atoms as a substituent on the phenyl group and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(1, 2 or 3-)piperazinyl]carbonylmethyl, 2-[(1, 2 or 3-)piperazinyl]carbonylethyl, 1-[(1, 2 or 3-)piperazinyl]carbonylethyl, 3-[(1, 2 or 3-)piperazinyl]carbonylpropyl, 4-[(1, 2 or 3-)piperazinyl]carbonylbutyl, 5-[(1, 2 or 3-)piperazinyl]carbonylpentyl, 6-[(1, 2 or 3-)piperazinyl]carbonylhexyl, 1,1-dimethyl-2-[(1, 2 or 3-)piperazinyl]carbonylethyl, 2-methyl-3-[(1, 2 or 3-)piperazinyl]carbonylpropyl, (4-benzyl-1-piperazinylcarbonyl)methyl, 2-[4-(2-phenylethyl)-1-piperazinylcarbonyl]ethyl, 1-[4-(3-phenylpropyl)-1-piperazinylcarbonyl]ethyl, 3-[4-(4-phenylbutyl)-1-piperazinylcarbonyl]propyl, 4-[4-(5-phenylpentyl)-1-piperazinylcarbonyl]butyl, 5-[4-(6-phenylpropy1)-1-piperazinylcarbonyl]pentyl, 6-(4-benzyl-1-piperazinylcarbonyl)hexyl, 1,1-dimethyl-2-(4-benzyl-1-piperazinylcarbonyl)ethyl, 2-methyl-3-(4-benzyl-1-piperazinylcarbonyl)propyl, [4-(3,4-methylenedioxybenzyl)-1-piperazinylcarbonyl]methyl, 2-{4-[2-(2,3-ethylenedioxyphenyl)ethyl]-1-piperazinylcarbonyl}ethyl, 1-{4-[3-(3,4-trimethylenedioxyphenyl)propyl]-1-piperazinylcarbonyl}ethyl, 3-{4-[4-(2,3-tetramethylenedioxyphenyl)butyl]-1-piperazinylcarbonyl}propyl, 4-{4-[5-(3,4-methylenedioxyphenyl)pentyl]-1-piperazinylcarbonyl}butyl, 5-{4-[3-(2,3-ethylenedioxyphenyl)propyl]-1-piperazinylcarbonyl}pentyl, 6-[4-(3,4-trimethylenedioxybenzyl)-1-piperazinylcarbonyl]hexyl, 1,1-dimethyl-2-[4-(2,3-tetramethylenedioxybenzyl)-1-piperazinylcarbonyl]ethyl, 2-methyl-3-[4-(3,4-methylenedioxybenzyl)-1-piperazinylcarbonyl]propyl, (3,4-dibenzyl-1-piperazinylcarbonyl)methyl, (3,4,5-tribenzyl-1-piperazinylcarbonyl)methyl, [2,4-di(3,4-methylenedioxybenzyl)-1-piperazinylcarbonyl]methyl, [2,4,6-tri(3,4-methylenedioxybenzyl)-1-piperazinylcarbonyl]methyl, and [3-benzyl-4-(3,4-methylenedioxybenzyl)-1-piperazinylcarbonyl]methyl groups.
Examples of the piperazinyl lower alkanoyl group which may be substituted on the piperazine ring with a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring include piperazinylalkanoyl groups whose alkanoyl moiety is a linear or branched alkanoyl group having 2 to 6 carbon atoms and which may be substituted on the piperazine ring with 1 to 3 phenylalkyl groups which may have a linear or branched alkylenedioxy group having 1 to 4 carbon atoms as a substituent on the phenyl ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms, such as 2-[(1, 2 or 3-)piperazinyl]acetyl, 3-[(1, 2 or 3-)piperazinyl]propionyl, 2-[(1, 2 or 3-)piperazinyl]propionyl, 4-[(1, 2 or 3-)piperazinyl]butyryl, 5-[(1, 2 or 3-)piperazinyl]pentanoyl, 6-[(1, 2 or 3-)piperazinyl]hexanoyl, 2,2-dimethyl-3-[(1, 2 or 3-)piperazinyl]propionyl, 2-methyl-3-[(1, 2 or 3-)piperazinyl]propionyl, 2-(4-benzyl-1-piperazinyl)acetyl, 3-[4-(2-phenylethyl)-1-piperazinyl]propionyl, 2-[4-(3-phenylpropyl)-1-piperazinyl]propionyl, 4-[4-(4-phenylbutyl)-1-piperazinyl]butyryl, 5-[4-(5-phenylpentyl)-1-piperazinyl]pentanoyl, 6-[4-(6-phenylpropyl)-1-piperazinyl]hexanoyl, 6-(4-benzyl-1-piperazinyl)hexanoyl, 2,2-dimethyl-3-(4-benzyl-1-piperazinyl)propionyl, 2-methyl-3-(4-benzyl-1-piperazinyl)propionyl, 2-[4-(3,4-methylenedioxybenzyl)-1-piperazinyl]acetyl, 3-{4-[2-(2,3-ethylenedioxyphenyl)ethyl]-1-piperazinyl}propionyl, 2-{4-[3-(3,4-trimethylenedioxyphenyl)propyl]-1-piperazinyl}propionyl, 4-{4-[4-(2,3-tetramethylenedioxyphenyl)butyl]-1-piperazinyl}butyryl, 5-{4-[5-(3,4-methylenedioxyphenyl)pentyl]-1-piperazinyl}pentanoyl, 5-{4-[3-(2,3-ethylenedioxyphenyl)propyl]-1-piperazinyl}pentanoyl, 6-[4-(3,4-trimethylenedioxybenzyl)-1-piperazinyl]hexanoyl, 2,2-dimethyl-3-[4-(2,3-tetramethylenedioxybenzyl)-1-piperazinyl]propionyl, 2-methyl-3-[4-(3,4-methylenedioxybenzyl)-1-piperazinyl]propionyl, 2-(3,4-dibenzyl-1-2-(3,4,5-tribenzyl-1-piperazinyl)acetyl, 2-[2,4-di(3,4-methylenedioxybenzyl)-1-piperazinyl]acetyl, 2-[2,4,6-tri(3,4-methylenedioxybenzyl)-1-piperazinyl]acetyl, and 2-[3-benzyl-4-(3,4-methylenedioxybenzyl)-1-piperazinyl]acetyl groups.
Examples of the morpholinocarbonyl substituted lower alkyl group include morpholinocarbonylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(2, 3 or 4-)morpholino]carbonylmethyl, 2-[(2, 3 or 4-)morpholino]carbonylethyl, 1-[(2, 3 or 4-)morpholino]carbonylethyl, 3-[(2, 3 or 4-)morpholino]carbonylpropyl, 4-[(2, 3 or 4-)morpholino]carbonylbutyl, 5-[(2, 3 or 4-)morpholino]carbonylpentyl, 6-[(2, 3 or 4-)morpholino]carbonylhexyl, 1,1-dimethyl-2-[(2, 3 or 4-)morpholino]carbonylethyl, and 2-methyl-3-[(2, 3 or 4-)morpholino]carbonylpropyl groups.
Examples of the imidazolyl lower alkanoyl group include imidazolylalkanoyl groups whose alkanoyl moiety is a linear or branched alkanoyl group having 2 to 6 carbon atoms such as 2-[(1, 2, 4 or 5-)imidazolyl]acetyl, 3-[(1, 2, 4 or 5-)imidazolyl]propionyl, 2-[(1, 2, 4 or 5-)imidazolyl]propionyl, 4-[(1, 2, 4 or 5-)imidazolyl]butyryl, 5-[(1, 2, 4 or 5-)imidazolyl]pentanoyl, 6-[(1, 2, 4 or 5-)imidazolyl]hexanoyl, 2,2-dimethyl-3-[(1, 2, 4 or 5-)imidazolyl]propionyl, and 2-methyl-3-[(1, 2, 4 or 5-)imidazolyl]propionyl groups.
Examples of the cycloalkylcarbonyl group include cycloalkylcarbonyl groups whose cycloalkyl moiety is a cycloalkyl group having 3 to 16 carbon atoms such as cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl, cycloheptylcarbonyl, cyclooctylcarbonyl, cyclononylcarbonyl, cyclodecylcarbonyl, cycloundecylcarbonyl, cyclododecylcarbonyl, cyclotridecylcarbonyl, cyclotetradecylcarbonyl, cyclopentadecylcarbonyl, and cyclohexadecylcarbonyl groups.
Examples of the amino substituted lower alkanoyl group which may have a lower alkyl group as a substituent include linear or branched alkanoyl groups having 2 to 6 carbon atoms substituted with an amino group which may have 1 or 2 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents such as aminoacetyl, 2-aminopropionyl, 3-aminopropionyl, 4-aminobutyryl, 5-aminopentanoyl, 6-aminohexanoyl, 2,2-dimethyl-3-aminopropionyl, 2-methyl-3-aminopropionyl, methylaminoacetyl, 2-ethylaminopropionyl, 3-propylaminopropionyl, 3-isopropylaminopropionyl, 4-butylaminobutyryl, 5-pentylaminopentanoyl, 6-hexylaminohexanoyl, dimethylaminoacetyl, 3-diisopropylaminopropionyl, (N-ethyl-N-propylamino)acetyl, and 2-(N-methyl-N-hexylamino)acetyl groups.
Examples of the lower alkylene group which may have a hydroxyl group as a substituent include, in addition to the above described lower alkylene groups, linear or branched alkylene groups having 1 to 6 carbon atoms which may have 1 to 3 hydroxyl groups as substituents such as 1-hydroxymethylene, 2-hydroxyethylene, 1-hydroxyethylene, 2-hydroxytrimethylene, 3-hydroxytrimethylene, 1-hydroxytrimethylene, 3-hydroxy-2-methyltrimethylene, 1-hydroxy-2-methyltrimethylene, 3-hydroxy-2,2-dimethyltrimethylene, 1-hydroxy-2,2-dimethyltrimethylene, 3-hydroxy-1-methyltrimethylene, 2-hydroxy-1-methyltrimethylene, 1-hydroxymethylmethylene, hydroxymethylmethylene, 2-hydroxymethyltrimethylene, 2-hydroxymethyl-2-methyltrimethylene, (2-hydroxyethyl)methylene, (1-hydroxyethyl)methylene, 4-hydroxytetramethylene, 2-hydroxytetramethylene, 3-hydroxytetramethylene, 1-hydroxytetramethylene, 5-hydroxypentamethylene, 4-hydroxypentamethylene, 3-hydroxypentamethylene, 2-hydroxypentamethylene, 1-hydroxypentamethylene, 6-hydroxyhexamethylene, 5-hydroxyhexamethylene, 4-hydroxyhexamethylene, 3-hydroxyhexamethylene, 2-hydroxyhexamethylene, 1-hydroxyhexamethylene, 1,2-dihydroxytrimethylene, 2,2,4-trihydroxytetramethylene, 1,2,6-trihydroxyhexamethylene, and 3,4,5-trihydroxypentamethylene groups.
Examples of the alkyl group which may have a hydroxyl group as a substituent include, in addition to the above described lower alkyl groups, linear or branched alkyl groups having 1 to 16 carbon atoms which may have 1 to 3 hydroxyl groups as substituents such as heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, 1-methylhexyl, hexadecyl, hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxypentyl, 5-hydroxypentyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, and 2-methyl-3-hydroxypropyl groups.
Examples of the hydroxyl group substituted alkyl group include linear or branched alkyl groups having 1 to 16 carbon atoms and 1 to 3 hydroxyl groups as substituents such as hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxypentyl, 5-hydroxypentyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, and 2-methyl-3-hydroxypropyl groups.
Examples of the cycloalkyl group which may have a substituent selected from the group consisting of a hydroxyl group and a lower alkyl group include, in addition to the above described cycloalkyl groups, cycloalkyl groups having 3 to 16 carbon atoms which may have 1 to 3 substituents selected from the group consisting of a hydroxyl group and a linear or branched alkyl group having 1 to 6 carbon atoms such as 2-hydroxycyclopropyl, 3-hydroxycyclobutyl, 3-hydroxycyclopentyl, 2-hydroxycyclohexyl, 4-hydroxycyclohexyl, 3-hydroxycycloheptyl, 4-hydroxycyclooctyl, 5-hydroxycyclononyl, 3-hydroxycyclodecyl, 4-hydroxycycloundecyl, 5-hydroxycyclododecyl, 6-hydroxycyclotridecyl, 7-hydroxycyclotetradecyl, 6-hydroxycyclopentadecyl, 8-hydroxycyclohexadecyl, 2,4-dihydroxycyclohexyl, 2,4,6-trihydroxycyclohexyl, 1-methylcyclopentyl, 2-ethylcyclopropyl, 3-n-propylcyclobutyl, 2-n-butylcyclohexyl, 4-n-pentylcycloheptyl, 4-n-hexylcyclooctyl, 2,3-dimethylcyclohexyl, 2,3,4-trimethylcyclohexyl, and 2-methyl-4-hydroxycyclohexyl groups.
Examples of the phenoxy lower alkyl group include phenoxyalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as phenoxymethyl, 2-phenoxyethyl, 1-phenoxyethyl, 3-phenoxypropyl, 4-phenoxybutyl, 1,1-dimethyl-2-phenoxyethyl, 5-phenoxypentyl, 6-phenoxyhexyl, 1-phenoxyisopropyl, and 2-methyl-3-phenoxypropyl groups.
Examples of the amino lower alkoxy group which may have a lower alkyl group as a substituent include linear or branched alkoxy groups having 1 to 6 carbon atoms substituted with an amino group which may have 1 or 2 linear or branched alkyl groups having 1 to 6 carbon atoms such as aminomethoxy, 2-aminoethoxy, 1-aminoethoxy, 3-aminopropoxy, 4-aminobutoxy, 5-aminopentyloxy, 6-aminohexyloxy, 1,1-dimethyl-2-aminoethoxy, 2-methyl-3-aminopropoxy, methylaminomethoxy, 1-ethylaminoethoxy, 2-propylaminoethoxy, 3-isopropylaminopropoxy, 4-butylaminobutoxy, 5-pentylaminopentyloxy, 6-hexylaminohexyloxy, dimethylaminomethoxy, 2-diethylaminoethoxy, 2-diisopropylaminoethoxy, (N-ethyl-N-propylamino)methoxy, and 2-(N-methyl-N-hexylamino)ethoxy groups.
Examples of the hydroxyl group substituted lower alkyl group include linear or branched alkyl groups having 1 to 6 carbon atoms which have 1 to 3 hydroxyl groups as substituents such as hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxypentyl, 5-hydroxypentyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, and 2-methyl-3-hydroxypropyl groups.
Examples of the amino group which may have a lower alkylsulfonyl as a substituent include amino groups which may have 1 or 2 linear or branched alkylsulfonyl groups having 1 to 6 carbon atoms as substituents such as amino, methylsulfonylamino, ethylsulfonylamino, propylsulfonylamino, isopropylsulfonylamino, butylsulfonylamino, tert-butylsulfonylamino, pentylsulfonylamino, hexylsulfonylamino, dimethylsulfonylamino, diethylsulfonylamino, dipropylsulfonylamino, dibutylsulfonylamino, dipentylsulfonylamino, dihexylsulfonylamino, N-methylsulfonyl-N-ethylsulfonylamino, N-ethylsulfonyl-N-propylsulfonylamino, N-methylsulfonyl-N-butylsulfonylamino, and N-methylsulfonyl-N-hexylsulfonylamino groups.
Examples of the lower alkynyl group include linear or branched alkynyl groups having 2 to 6 carbon atoms such as ethynyl, 2-propynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 2-pentynyl, and 2-hexynyl groups.
Examples of the anilino group which may have a halogen atom as a substituent on the phenyl ring include anilino groups which may have 1 to 3 halogen atoms as substituents on the phenyl ring such as anilino, 2-fluoroanilino, 3-fluoroanilino, 4-fluoroanilino, 2-bromoanilino, 3-bromoanilino, 4-bromoanilino, 2-iodoanilino, 3-iodoanilino, 4-iodoanilino, 2,3-dibromoanilino, 2,4-diiodoanilino, 2,5-difluoroanilino, 2,6-dichloroanilino, 2,4,6-trichloroanilino, 2,6-difluoroanilino, 3,5-difluoroanilino, 2,6-difluoroanilino, 2-chloroanilino, 3-chloroanilino, 4-chloroanilino, 2,3-dichloroanilino, 2,4-dichloroanilino, 2,5-dichloroanilino, 3,4-dichloroanilino, 2,6-dichloroanilino, 3,5-dichloroanilino, 2,4,6-trifluoroanilino, 2,4-difluoroanilino, and 3,4-difluoroanilino groups.
Examples of the piperazinyl group which may have a lower alkyl group as a substituent on the piperazine ring include piperazinyl groups which may have 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the piperazine ring such as (1-, 2- or 3-)piperazinyl, 4-methyl-(1-, 2- or 3-)piperazinyl, 2,3-dimethyl-(1- or 5-)piperazinyl, and 2,3,4-trimethyl-(1-, 5- or 6-)piperazinyl groups.
Examples of the pyrrolidinyl group which may have an oxo group as a substituent on the pyrrolidine ring include pyrrolidinyl groups which may have 1 or 2 oxo groups as substituents on the pyrrolidine ring such as (1-, 2- or 3-)pyrrolidinyl, 2-oxo-(1-, 3-, 4- or 5-)pyrrolidinyl, 3-oxo-(1-, 2-, 4- or 5-)pyrrolidinyl, 2,3-dioxo-(1-, 4- or 5-)pyrrolidinyl, and 2,5-dioxo-(1-, 3- or 4-)pyrrolidinyl groups.
Examples of the lower alkanoyl amino group include linear or branched alkanoyl amino groups having 2 to 6 carbon atoms which have 1 to 3 halogen atoms as substituents such as acetyl amino, propionyl amino, butyryl amino, pentanoyl amino, 2-methylpropionyl amino, and hexanoyl amino groups.
Examples of the phenyl group which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a lower alkyl group; a lower alkoxy group which may have a halogen atom as a substituent; a halogen atom; an amino lower alkoxy group which may have a lower alkyl group as a substituent; a hydroxyl group substituted lower alkyl group; a phenyl lower alkyl group; a lower alkynyl group; an amino group which may have a lower alkylsulfonyl group as a substituent; a lower alkylthio group; a cycloalkyl group; a phenylthio group; an adamantyl group; an anilino group which may have a halogen atom as a substituent on the phenyl ring; a lower alkoxycarbonyl group; a piperazinyl group which may have a lower alkyl group as a substituent on the piperazine ring; a lower alkanoylamino group; a cyano group; a pyrrolidinyl group which may have an oxo group as a substituent on the pyrrolidine ring; and a phenoxy group include phenyl groups which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms; a linear or branched alkoxy group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms; a halogen atom; an aminoalkoxy group whose alkoxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms and which may have 1 or 2 linear or branched alkyl groups having 1 to 6 carbon atom as substituents; a linear or branched alkyl group having 1 to 6 carbon atoms and 1 to 3 hydroxyl groups as substituents; a phenylalkyl group whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms; a linear or branched alkynyl group having 2 to 6 carbon atoms; an amino group which may have 1 or 2 linear or branched alkylsulfonyl groups having 1 to 6 carbon atoms as substituents; a linear or branched alkylthio group having 1 to 6 carbon atoms; a cycloalkyl group having 3 to 16 carbon atoms; a phenylthio group; an adamantyl group; an anilino group which may have 1 to 3 halogen atoms as substituents on the phenyl ring; an alkoxycarbonyl group whose akloxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms; an amino group which may have 1 or 2 linear or branched alkanoyl groups having 2 to 6 carbon atoms; a cyano group; a piperazinyl group which may have 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the piperazine ring; a pyrrolidinyl group which may have 1 or 2 oxo groups as substituents on the pyrrolidine ring; and a phenoxy group such as phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 2-isopropylphenyl, 4-isopropylphenyl, 3-butylphenyl, 4-pentylphenyl, 4-hexylphenyl, 3,4-dimethylphenyl, 3,4-diethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4,5-trimethyiphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 4-isopropoxyphenyl, 3-butoxyphenyl, 4-pentyloxyphenyl, 4-hexyloxyphenyl, 3,4-dimethoxyphenyl, 3,4-diethoxyphenyl, 2,4-dimethoxyphenyl, 2,5-dimethoxyphenyl, 2,6-dimethoxyphenyl, 3,4,5-trimethoxyphenyl, 2-trifluoromethoxyphenyl, 3-trifluoromethoxyphenyl, 4-trifluoromethoxyphenyl, 2-(bromomethoxy)phenyl, 3-(2-chloroethoxy)phenyl, 4-(2,3-dichloropropoxy)phenyl, 4-(4-fluorobutoxy)phenyl, 3-(5-chloropentyloxy)phenyl, 4-(5-bromohexyloxy)phenyl, 4-(5,6-dibromohexyloxy)phenyl, 3,4-di(trifluoromethoxy)phenyl, 3,4-di(4,4,4-trichlorobutoxy)phenyl, 2,4-di(3-chloro-2-methoxypropyl)phenyl, 2,5-di(3-chloropropoxy)phenyl, 2,6-di(2,2,2-trifluoroethoxy)phenyl, 3,4,5-tri(trifluoromethoxy)phenyl, 4-(2,2,2-trichloroethoxy)phenyl, 2-methyl-4-trifluoromethoxyphenyl, 3-ethyl-4-trichloromethoxyphenyl, 2-methoxy-4-trifluoromethoxyphenyl, 3-ethoxy-4-trichloromethoxyphenyl, 2-methyl-3-trifluoromethoxy-4-trifluoromethoxyphenyl, 2-phenoxyphenyl, 3-phenoxyphenyl, 4-phenoxyphenyl, 2,3-diphenoxyphenyl, 3,4-diphenoxyphenyl, 2,6-diphenoxyphenyl, 3,4,5-triphenoxyphenyl, 2-methyl-4-phenoxyphenyl, 3-ethyl-4-phenoxyphenyl, 2-methoxy-4-phenoxyphenyl, 3-ethoxy-4-phenoxyphenyl, 2-methyl-3-phenoxy-4-trifluoromethoxyphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 2,5-dichlorophenyl, 3,4-dichlorophenyl, 2,6-dichlorophenyl, 3,5-dichlorophenyl, 2,4,6-trichlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2,5-difluorophenyl, 2,4-difluorophenyl, 3,4-difluorophenyl, 3,5-difluorophenyl, 2,6-difluorophenyl, 2,4,6-trifluorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2-iodophenyl, 3-iodophenyl, 4-iodophenyl, 2,3-dibromophenyl, 2,4-diiodophenyl, 4-methylthiophenyl, 4-cyclohexylphenyl, 4-chloro-2-anilinophenyl, 2-(4-chloro anilino)-5-ethoxy carbonylphenyl, 4-[2-(N,N-diethylamino)ethoxy]phenyl, 4-(4-methyl-1-piperazinyl)phenyl, 4-(2-oxo-1-pyrrolidinyl)phenyl, 4-methylsulfonylaminophenyl, 4-(2-hydroxyethyl)phenyl, 4-benzylphenyl, 4-ethynylphenyl, 4-phenylthiophenyl, 4-(1-adamantyl)phenyl, 5-acetylamino-2-chlorophenyl, 2-propanoylaminophenyl, 3-cyanophenyl, 2-cyanophenyl, 4-cyanophenyl, 3,4-dicyanophenyl, and 3,4,5-tricyanophenyl groups.
Examples of the phenyl lower alkyl group which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a halogen atom, a lower alkoxy group which may have a halogen atom as a substituent, and a lower alkyl group include, in addition to the above described phenyl lower alkyl groups, phenylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms and which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a halogen atom, a linear or branched alkoxy group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, and a linear or branched alkyl group having 1 to 6 carbon atoms such as 4-fluorobenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 2-(2-fluorophenyl)ethyl, 2-(4-fluorophenyl)ethyl, 2-(4-chlorophenyl)ethyl, 3,4-dibromobenzyl, 3,4-diiodobenzyl, 2,4-difluorobenzyl, 2,5-dichlorobenzyl, 2,6-dichlorobenzyl, 3,4,5-trifluorobenzyl, 3-(4-chlorophenyl)propyl, 1-(2-bromophenyl)ethyl, 4-(3-fluorophenyl)butyl, 5-(4-iodophenyl)pentyl, 6-(4-chlorophenyl)hexyl, 1,1-dimethyl-2-(3-fluorophenyl)ethyl, 2-methyl-3-(4-chlorophenyl)propyl, 2-methylbenzyl, 2-(3-methylphenyl)ethyl, 3-(4-methylphenyl)propyl, 1-(2-ethylphenyl)ethyl, 4-(3-ethylphenyl)butyl, 5-(4-ethylphenyl)pentyl, 6-(4-isopropylphenyl)hexyl, 1,1-dimethyl-2-(3-butylphenyl)ethyl, 2-methyl-3-(4-pentylphenyl)propyl, 4-hexylbenzyl, 3,4-dimethylbenzyl, 3,4-diethylbenzyl, 2,4-dimethylbenzyl, 2,5-dimethylbenzyl, 2,6-dimethylbenzyl, 3,4,5-trimethylbenzyl, 2-methoxybenzyl, 2-(2-methoxyphenyl)ethyl, 2-(3-methoxyphenyl)ethyl, 2-(4-methoxyphenyl)ethyl, 4-methoxybenzyl, 1-(2-ethoxyphenyl)ethyl, 3-(3-ethoxyphenyl)propyl, 4-(4-ethoxyphenyl)butyl, 5-(4-isopropoxyphenyl)pentyl, 6-(3-butoxyphenyl)hexyl, 1,1-dimethyl-2-(4-pentyloxyphenyl)ethyl, 2-methyl-3-(4-hexyloxyphenyl)propyl, 3,4-dimethoxybenzyl, 3,4-diethoxybenzyl, 2,4-dimethoxybenzyl, 2,5-dimethoxybenzyl, 2,6-dimethoxybenzyl, 3,4,5-trimethoxybenzyl, 2-trifluoromethoxybenzyl, 3-trifluoromethoxybenzyl, 4-trifluoromethoxybenzyl, 2-[2-(bromomethoxy)phenyl]ethyl, 1-[3-(2-chloroethoxy)phenyl]ethyl, 3-[4-(2,3-dichloropropoxy)phenyl]propyl, 4-[4-(4-fluorobutoxy)phenyl]butyl, 5-[3-(5-chloropentyloxy)phenyl]pentyl, 6-[4-(5-bromohexyloxy)phenyl]hexyl, 1,1-dimethyl-2-[4-(5,6-dibromohexyloxy)phenyl]ethyl, 3,4-di(trifluoromethoxy)benzyl, 3,4-di(4,4,4-trichlorobutoxy)benzyl, 2,4-di(3-chloro-2-methoxypropyl)benzyl, 2,5-di(3-chloropropoxy)benzyl, 2,6-di(2,2,2-trifluoroethoxy)benzyl, 3,4,5-tri(trifluoromethoxy)benzyl, 4-(2,2,2-trichloroethoxy)benzyl, 2-methyl-4-trifluoromethoxybenzyl, 3-ethyl-4-trichloromethoxybenzyl, 2-methoxy-4-trifluoromethoxybenzyl, 3-ethoxy-4-trichloromethoxybenzyl, 2-methyl-3-trifluoromethoxy-4-trifluoromethoxybenzyl, 2-chloro-3-methylbenzyl, 4-fluoro-2-trifluoromethoxybenzyl, and 3-chloro-2-methyl-4-methoxybenzyl groups.
Examples of the phenyl lower alkyl group which has a lower alkylenedioxy group as a substituent on the phenyl ring include phenylalkyl groups which have a linear or branched alkylenedioxy group having 1 to 4 carbon atoms as a substituent on the phenyl ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as 3,4-methylenedioxybenzyl, 3,4-trimethylenedioxybenzyl, 2-(2,3-ethylenedioxyphenyl)ethyl, 1-(3,4-trimethylenedioxyphenyl)ethyl, 3-(2,3-tetramethylenedioxyphenyl)propyl, 4-(3,4-methylenedioxyphenyl)butyl, 5-(2,3-ethylenedioxyphenyl)pentyl, 6-(3,4-trimethylenedioxyphenyl)hexyl, 1,1-dimethyl-2-(2,3-metylenedioxyphenyflethyl, and 2-methyl-3-(3,4-ethylenedioxyphenyl)propyl groups.
Examples of the amino group which may have a lower alkanoyl group as a substituent include amino groups which may have a linear or branched alkanoyl group having 1 to 6 carbon atoms as a substituent such as amino, N-acetylamino, N-formylamino, N-propionylamino, N-butyrylamino, N-isobutyrylamino, N-pentanoylamino, N-tert-butylcarbonylamino, and N-hexanoylamino groups.
Examples of the 1,2,3,4-tetrahydroquinolyl group which may have, on the tetrahydroquinoline ring, 1 to 3 substituents selected from the group consisting of an oxo group, a lower alkoxy group, and a lower alkylenedioxy group include 1,2,3,4-tetrahydroquinolyl groups which may have, on the tetrahydroquinoline ring, 1 to 3 substituents selected from the group consisting of an oxo group, a linear or branched alkoxy group having 1 to 6 carbon atoms, and a linear or branched alkylenedioxy group having 1 to 4 carbon atoms such as (1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl, 2-oxo-(1, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl, 2-oxo-6,7-methylenedioxy-(1, 3, 4, 5 or 8-)1,2,3,4-tetrahydroquinolyl, 4-oxo-(1, 2, 3, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl, 2,4-dioxo-(1, 3, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl, 2,4-dioxo-6,7-methylenedioxy-(1, 3, 5 or 8-)1,2,3,4-tetrahydroquinolyl, 5,6-ethylenedioxy-(1, 2, 3, 4, 7 or 8-)1,2,3,4-tetrahydroquinolyl, 7,8-trimethylenedioxy-(1, 2, 3, 4, 5 or 6-)1,2,3,4-tetrahydroquinolyl, 6,7-tetramethylenedioxy-(1, 2, 3, 4, 5 or 8-)1,2,3,4-tetrahydroquinolyl, 5-methoxy-2-oxo-(1, 3, 4, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl, and 2-oxo-6,7-ethylenedioxy-(1, 3, 4, 5 or 8-)1,2,3,4-tetrahydroquinolyl groups.
Examples of the cycloalkyl lower alkyl group include cycloalkylalkyl groups having 3 to 16 carbon atoms whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as cyclopropylmethyl, cyclohexylmethyl, 2-cyclopropylethyl, 1-cyclobutylethyl, 3-cyclopentylpropyl, 4-cyclohexylbutyl, 5-cycloheptylpentyl, 6-cyclooctylhexyl, 1,1-dimethyl-2-cyclononylethyl, 2-methyl-3-cyclodecylpropyl, cycloundecylmethyl, 2-cyclododecylethyl, 1-cyclotridecylethyl, 3-cyclotetradecylpropyl, 4-cyclopentadecylbutyl, and 5-cyclohexadecylpentyl groups.
Examples of the pyridyl lower alkyl group include pyridylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2, 3 or 4-)pyridylmethyl, 2-[(2, 3 or 4-)pyridyl]ethyl, 1-[(2, 3 or 4-)pyridyl]ethyl, 3-[(2, 3 or 4-)pyridyl]propyl, 4-[(2, 3 or 4-)pyridyl]butyl, 1,1-dimethyl-2-[(2, 3 or 4-)pyridyl]ethyl, 5-[(2, 3 or 4-)pyridyl]pentyl, 6-[(2, 3 or 4-)pyridyl]hexyl, 1-[(2, 3 or 4-)pyridyl]isopropyl, and 2-methyl-3-[(2, 3 or 4-)pyridyl]propyl groups.
Examples of the amino group substituted lower alkyl group which may have a substituent selected from the group consisting of a lower alkyl group and a lower alkanoyl group include linear or branched alkyl groups having 1 to 6 carbon atoms and an amino group which may have 1 or 2 substituents selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms and a linear or branched alkanoyl group having 1 to 6 carbon atoms such as aminomethyl, 2-aminoethyl, 1-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl, 1,1-dimethyl-2-aminoethyl, 2-methyl-3-aminopropyl, methylaminomethyl, 1-ethylaminoethyl, 2-propylaminoethyl, 3-isopropylaminopropyl, 4-butylaminobutyl, 5-pentylaminopentyl, 6-hexylaminohexyl, dimethylaminomethyl, 2-diisopropylaminoethyl, (N-ethyl-N-propylamino)methyl, 2-(N,N-dimethylamino)ethyl, 2-(N-methyl-N-hexylamino)ethyl, formylaminomethyl, acetylaminomethyl, 1-propionylaminoethyl, 2-acetylaminoethyl, 3-butyrylaminopropyl, 4-pentanoylaminobutyl, 5-hexanoylaminopentyl, 6-acetylaminohexyl, N-methyl-N-acetylaminomethyl, 2-(N-ethyl-N-propanoylamino)ethyl, (N-ethyl-N-butyrylamino)methyl, 2-(N-methyl-N-hexanoylamino)ethyl, and 3-(N,N-dimethylamino)propyl groups.
Examples of the lower alkoxy lower alkyl group include linear or branched alkyl groups having 1 to 6 carbon atoms which have a linear or branched alkoxy group having 1 to 6 carbon atoms, as a substituent such as methoxymethyl, 1-ethoxyethyl, 2-methoxyethyl, 2-propoxyethyl, 3-isopropoxypropyl, 4-butoxybutyl, 5-pentyloxypentyl, 6-hexyloxyhexyl, 1,1-dimethyl-2-methoxyethyl, 2-methyl-3-ethoxypropyl, and 3-methoxypropyl groups.
Examples of the 1,2,3,4-tetrahydroisoquinolylcarbonyl substituted lower alkyl group include 1,2,3,4-tetrahydroisoquinolylcarbonyl-alkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroisoquinolylcarbonylmethyl, 2-[(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroisoquinolylcarbonyl]ethyl, 1-[((1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroisoquinolylcarbonyl)ethyl, 3-[(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroisoquinolylcarbonyl]propyl, 4-[(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroisoquinolylcarbonyl]butyl, 1,1-dimethyl-2-[(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroisoquinolylcarbonyl]ethyl, 5-[(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroisoquinolylcarbonyl]pentyl, 6-[(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroisoquinolylcarbonyl]hexyl, 1-[(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroisoquinolylcarbonyl]isopropyl, and 2-methyl-3-[(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroisoquinolylcarbonyl]propyl groups.
Examples of the piperidinylcarbonyl group which may have, on the piperidine ring, a substituent selected from the group consisting of a lower alkoxycarbonyl group, a phenyl lower alkyl group, and a furyl lower alkyl group include piperidinylcarbonyl groups which may have, on the piperidine ring, 1 to 3 substituents selected from the group consisting of an alkoxycarbonyl group whose alkoxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms, a phenylalkyl group whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms, and a furylalkyl group whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1, 2, 3 or 4-)piperidinylcarbonyl, 1-benzyl-(2, 3 or 4-)piperidinylcarbonyl, 1-(2 or 3-)furylmethyl-(2, 3 or 4-)piperidinylcarbonyl, 1-(2-phenylethyl)-(2, 3 or 4-)piperidinylcarbonyl, 1-{2-[(1 or 2-)furyl]ethyl}-(2, 3 or 4-)piperidinylcarbonyl, 1-(1-phenylethyl)-(2, 3 or 4-)piperidinylcarbonyl, 1-{3-[(1 or 2-)furyl]propyl]}-(2, 3 or 4-)piperidinylcarbonyl, 1-(3-phenylpropyl)-(2, 3 or 4-)piperidinylcarbonyl, 1-{1-[(1 or 2-)furyl]ethyl]}-(2, 3 or 4-)piperidinylcarbonyl, 1-(4-phenylbutyl)-(2, 3 or 4-)piperidinylcarbonyl, 1-{4-[(1 or 2-)furyl]butyl]}-(2, 3 or 4-)piperidinylcarbonyl, 1-(5-phenylpentyl)-(2, 3 or 4-)piperidinylcarbonyl, 1-{5-[(1 or 2-)furyl]pentyl]}-(2, 3 or 4-)piperidinylcarbonyl, 1-(6-phenylhexyl)-(2, 3 or 4-)piperidinylcarbonyl, 1-{6-[(1 or 2-)furyl]hexyl]}-(2, 3 or 4-)piperidinylcarbonyl, 1,2-dibenzyl-(3, 4, 5 or 6-)piperidinylcarbonyl, 1,3-di(1 or 2-)furylmethyl-(2, 4, 5 or 6-)piperidinylcarbonyl, 1,3,5-tribenzyl-(2, 4 or 6-)piperidinylcarbonyl, 1,2,6-tri(1 or 2-)furylmethyl-(3, 4 or 5-)piperidinylcarbonyl, 1-benzyl-3-(1 or 2-)furylmethyl-(2, 4, 5 or 6-)piperidinylcarbonyl, 1-{1-[(1 or 2-)furyl]ethyl]}-(2, 3 or 4-)piperidinylcarbonyl, 1-methoxycarbonyl-(2, 3 or 4-)piperidinylcarbonyl, 1-ethoxycarbonyl-(2, 3 or 4-)piperidinylcarbonyl, 1-propoxycarbonyl-(2, 3 or 4-)piperidinylcarbonyl, 1-butoxycarbonyl-(2, 3 or 4-)piperidinylcarbonyl, 1-tert-butoxycarbonyl-(2, 3 or 4-)piperidinylcarbonyl, 1-pentyloxycarbonyl-(2, 3 or 4-)piperidinylcarbonyl, 1-hexyloxycarbonyl-(2, 3 or 4-)piperidinylcarbonyl, 1,2-dimethoxycarbonyl-(3, 4, 5 or 6-)piperidinylcarbonyl, 1,2,6-triethoxycarbonyl-(3, 4 or 5-)piperidinylcarbonyl, 1-(1 or 2-)furylmethyl-3-tert-butoxycarbonyl-(3, 4, 5 or 6-)piperidinylcarbonyl, 1-benzyl-2-methoxycarbonyl-(2, 4, 5 or 6-)piperidinylcarbonyl, and 1-(1 or 2-)furylmethyl-2,4-dimethoxycarbonyl-(3, 5 or 6-)piperidinylcarbonyl groups.
Examples of the thiazolidinyl lower alkanoyl group which may have an oxo group as a substituent on the thiazolidine ring include thiazolidinylalkanoyl groups which may have 1 to 3 oxo groups as substituents on the thiazolidine ring and whose alkanoyl moiety is a linear or branched alkanoyl group having 2 to 6 carbon atoms such as 2-[(2, 3, 4 or 5-)thiazolidinyl]acetyl, 3-[(2, 3, 4 or 5-)thiazolidnyl]propionyl, 2-[(2, 3, 4 or 5-)thiazolidinyl]propionyl, 4-[(2, 3, 4 or 5-)thiazolidinyl]butyryl, 5-[(2, 3, 4 or 5-)1,2,4-thiazolidinyl]pentanoyl, 6-[(2, 3, 4 or 5-)thiazolidinyl]hexanoyl, 2,2-dimethyl-3-[(2, 3, 4 or 5-)thiazolidinyl]propionyl, 2-methyl-3-[(2, 3, 4 or 5-)thiazolidinyl]propionyl, 2,4-dioxo-(3 or 5-)thiazolidinylacetyl, 3-[2-oxo-(3, 4 or 5-)thiazolidinyl]propionyl, 2-[4-oxo-(2, 3 or 5-)thiazolidinyl]propionyl, 4-[5-oxo-(2, 3 or 4-)thiazolidinyl]butyryl, 5-[2,5-dioxo-(3 or 4-)thiazolidinyl]pentanoyl, 6-[2,4,5-trioxo-3-thiazolidinyl]hexanoyl, 2-[4,5-dioxo-(2 or 3-)thiazolidinyl]acetyl, 2,2-dimethyl-3-[2,4-dioxo-(3 or 5-)thiazolidinyl]propionyl, and 2-methyl-3-[2,4-dioxo-(3 or 5-)thiazolidinyl]propionyl groups.
Examples of the piperidinyl group which may be substituted on the piperidine ring with a group selected from the group consisting of a lower alkoxycarbonyl group, a phenyl lower alkyl group, a lower alkyl group, a benzoyl group and a furyl lower alkyl group include piperidinyl groups which may be substituted on the piperidine ring with 1 to 3 groups selected from the group consisting of an alkoxycarbonyl group whose alkoxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms, a phenylalkyl group whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms, a linear or branched alkyl group having 1 to 6 carbon atoms, a benzoyl group, and a furylalkyl group whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1, 2, 3 or 4-)piperidinyl, 1-benzyl-(2, 3 or 4-)piperidinyl, 1-(2 or 3-)furylmethyl-(2, 3 or 4-)piperidinyl, 1-(2-phenylethyl)-(2, 3 or 4-)piperidinyl, 1-{2-[(1 or 2-)furyl]ethyl}-(2, 3 or 4-)piperidinyl, 1-(1-phenylethyl)-(2, 3 or 4-)piperidinyl, 1-{3-[(1 or 2-)furyl]propyl]}-(2, 3 or 4-)piperidinyl, 1-(3-phenylpropyl)-(2, 3 or 4-)piperidinyl, 1-{1-[(1 or 2-)furyl]ethyl]}-(2, 3 or 4-)piperidinyl, 1-(4-phenylbutyl)-(2, 3 or 4-)piperidinyl, 1-{4-[(1 or 2-)furyl]butyl]}-(2, 3 or 4-)piperidinyl, 1-(5-phenylpentyl)-(2, 3 or 4-)piperidinyl, 1-{5-[(1 or 2-)furyl]pentyl]}-(2, 3 or 4-)piperidinyl, 1-(6-phenylhexyl)-(2, 3 or 4-)piperidinyl, 1-{6-[(1 or 2-)furyl]hexyl]}-(2, 3 or 4-)piperidinyl, 1,2-dibenzyl-(3, 4, 5 or 6-)piperidinyl, 1,3-di(1 or 2-)furylmethyl-(2, 4, 5 or 6-)piperidinyl, 1,3,5-tribenzyl-(2, 4 or 6-)piperidinyl, 1,2,6-tri(1 or 2-)furylmethyl-(3, 4 or 5-)piperidinyl, 1-benzyl-3-(1 or 2-)furylmethyl-(2, 4, 5 or 6-)piperidinyl, 1-{1-[(1 or 2-)furyl]ethyl]}-(2, 3 or 4-)piperidinyl, 1-benzoyl-(2, 3 or 4-)piperidinyl, 1,2-dibenzoyl-(3, 4, 5 or 6-)piperidinyl, 1,3,5-tribenzoyl-(2, 4 or 6-)piperidinyl, 1-methyl-(2, 3 or 4-)piperidinyl, 1-ethyl-(2, 3 or 4-)piperidinyl, 1-propyl-(2, 3 or 4-)piperidinyl, 1-isopropyl-(2, 3 or 4-)piperidinyl, 1-butyl-(2, 3 or 4-)piperidinyl, 1-isobutyl-(2, 3 or 4-)piperidinyl, 1-tert-butyl-(2, 3 or 4-)piperidinyl, 1-pentyl-(2, 3 or 4-)piperidinyl, 1-hexyl-(2, 3 or 4-)piperidinyl, 1,2-dimethyl-(3, 4, 5 or 6-)piperidinyl, 1,2,6-trimethyl-(3, 4 or 5-)piperidinyl, 1-methyl-3-benzyl-(3, 4, 5 or 6-)piperidinyl, 1-benzoyl-2-methyl-(2, 4, 5 or 6-)piperidinyl, 1-(1 or 2-)furylmethyl-2,4-dimethyl-(3, 5 or 6-)piperidinyl, 1-methoxycarbonyl-(2, 3 or 4-)piperidinyl, 1-ethoxycarbonyl-(2, 3 or 4-)piperidinyl, 1-propoxycarbonyl-(2, 3 or 4-)piperidinyl, 1-butoxycarbonyl-(2, 3 or 4-)piperidinyl, 1-tert-butoxycarbonyl-(2, 3 or 4-)piperidinyl, 1-pentyloxycarbonyl-(2, 3 or 4-)piperidinyl, 1-hexyloxycarbonyl-(2, 3 or 4-)piperidinyl, 1,2-dimethoxycarbonyl-(3, 4, 5 or 6-)piperidinyl, 1,2,6-triethoxycarbonyl-(3, 4 or 5-)piperidinyl, 1-methyl-3-tert-butoxycarbonyl-(3, 4, 5 or 6-)piperidinyl, 1-benzoyl-2-methoxycarbonyl-(2, 4, 5 or 6-)piperidinyl, 1-(1 or 2-)furylmethyl-2,4-dimethoxycarbonyl-(3, 5 or 6-)piperidinyl, and 1-benzyl-2,4-dimethoxycarbonyl-(3, 5 or 6-)piperidinyl groups.
Examples of the carbonyl lower alkyl group substituted with a group:
(hereinafter called “A group”) include A group substituted carbonylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as A group substituted carbonylmethyl, 2-A group substituted carbonylethyl, 1-A group substituted carbonylethyl, 3-A group substituted carbonylpropyl, 4-A group substituted carbonylbutyl, 1,1-dimethyl-2-A group substituted carbonylethyl, 5-A group substituted carbonylpentyl, 6-A group substituted carbonylhexyl, 1-A group substituted carbonylisopropyl, and 2-methyl-3-A group substituted carbonylpropyl groups.
Examples of the carbonyl lower alkyl group substituted with a group:
wherein R34 is an oxo group or a phenyl group, and d is an integer of 0 to 3 (hereinafter called “B group”), include B group substituted carbonylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as B group substituted carbonylmethyl, 2-B group substituted carbonylethyl, 1-B group substituted carbonylethyl, 3-B group substituted carbonylpropyl, 4-B group substituted carbonylbutyl, 1,1-dimethyl-2-B group substituted carbonylethyl, 5-B group substituted carbonylpentyl, 6-B group substituted carbonylhexyl, 1-B group substituted carbonylisopropyl, and 2-methyl-3-B group substituted carbonylpropyl groups.
Examples of the pyrrolidinyl lower alkyl group include pyrrolidinylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1-, 2-, or 3-)pyrrolidinylmethyl, 2-[(1-, 2-, or 3-)pyrrolidinyl]ethyl, 1-[(1-, 2-, or 3-)pyrrolidinyl]ethyl, 3-[(1-, 2-, or 3-)pyrrolidinyl]propyl, 4-[(1-, 2-, or 3-)pyrrolidinyl]butyl, 5-[(1-, 2-, or 3-)pyrrolidinyl]pentyl, 6-[(1-, 2-, or 3-)pyrrolidinyl]hexyl, 1,1-dimethyl-2-[(1-, 2-, or 3-)pyrrolidinyl]ethyl, and 2-methyl-3-[(1-, 2-, or 3-)pyrrolidinyl]propyl groups.
Examples of the morpholino lower alkyl group include morpholinoalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2-, 3- or 4-)morpholinomethyl, 2-[(2-, 3- or 4-)morpholino]ethyl, 1-[(2-, 3- or 4-)morpholino]ethyl, 3-[(2-, 3- or 4-)morpholino]propyl, 4-[(2-, 3- or 4-)morpholino]butyl, 5-[(2-, 3- or 4-)morpholino]pentyl, 6-[(2-, 3- or 4-)morpholino]hexyl, 1,1-dimethyl-2-[(2-, 3- or 4-)morpholino]ethyl, and 2-methyl-3-[(2-, 3- or 4-)morpholino]propyl groups.
Examples of the phenyl lower alkenyl group include phenylalkenyl groups whose alkenyl moiety is a linear or branched alkenyl group having 2 to 6 carbon atoms and which have 1 to 3 double bonds such as styryl, 3-phenyl-2-propenyl group (trivial name: cinnamyl group), 4-phenyl-2-butenyl, 4-phenyl-3-butenyl, 5-phenyl-4-pentenyl, 5-phenyl-3-pentenyl, 6-phenyl-5-hexenyl, 6-phenyl-4-hexenyl, 6-phenyl-3-hexenyl, 4-phenyl-1,3-butadienyl, and 6-phenyl-1,3,5-hexatrienyl groups.
Examples of the anilinocarbonyl lower alkyl group which may have a lower alkyl group as a substituent on the phenyl ring include anilinocarbonylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms and which may have 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the phenyl ring such as anilinocarbonylmethyl, 2-anilinocarbonylethyl, 1-anilinocarbonylethyl, 3-anilinocarbonylpropyl, 4-anilinocarbonylbutyl, 5-anilinocarbonylpentyl, 6-anilinocarbonylhexyl, 1,1-dimethyl-2-anilinocarbonylethyl, 2-methyl-3-anilinocarbonylpropyl, (4-methylanilinocarbonyl)methyl, 2-(3-methylanilinocarbonyl)ethyl, 3-(4-methylanilinocarbonyl)propyl, 1-(2-ethylanilinocarbonyl)ethyl, 4-(3-ethylanilinocarbonyl)butyl, 5-(4-ethylanilinocarbonyl)pentyl, 6-(4-isopropylanilinocarbonyl)hexyl, 1,1-dimethyl-2-(3-butylanilinocarbonyl)ethyl, 2-methyl-3-(4-pentylanilinocarbonyl)propyl, 4-hexylanilinocarbonylmethyl, 3,4-dimethylanilinocarbonylmethyl, 3,4-diethylanilinocarbonylmethyl, 2,4-dimethylanilinocarbonylmethyl, 2,5-dimethylanilinocarbonylmethyl, 2,6-dimethylanilinocarbonylmethyl, and 3,4,5-trimethylanilinocarbonylmethyl groups.
Examples of the piperazinyl lower alkyl group which may have, on the piperazine ring, a substituent selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group which may have a lower alkylenedioxy group as a substituent on the phenyl ring include piperazinylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms and which may have, on the piperazine ring, 1 to 3 substituents selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms and a phenylalkyl group which may have a linear or branched alkylenedioxy group having 1 to 4 carbon atoms as a substituent on the phenyl ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(1-, 2- or 3-)piperazinyl]methyl, 2-[(1-, 2- or 3-)piperazinyl]ethyl, 1-[(1-, 2- or 3-)piperazinyl]ethyl, 3-[(1-, 2- or 3-)piperazinyl]propyl, 4-[(1-, 2- or 3-)piperazinyl]butyl, 5-[(1-, 2- or 3-)piperazinyl]pentyl, 6-[(1-, 2- or 3-)piperazinyl]hexyl, 1,1-dimethyl-2-[(1-, 2- or 3-)piperazinyl]ethyl, 2-methyl-3-[(1-, 2- or 3-)piperazinyl]propyl, [1-methyl-(2-, 3- or 4-)piperazinyl]methyl, 2-[1-ethyl-(2-, 3- or 4-)piperazinyl]ethyl, 1-[4-propyl-(1-, 2- or 3-)piperazinyl]ethyl, 3-[3-isopropyl-(1-, 2-, 4-, 5- or 6-)piperazinyl]propyl, 4-[2-butyl-(1-, 3-, 4-, 5- or 6-)piperazinyl]butyl, 5-[1-isobutyl-(2-, 3- or 4-)piperazinyl]pentyl, 3-[4-methyl-(1-, 2- or 3-)piperazinyl]propyl, 6-[1-tert-butyl-(2-, 3- or 4-)piperazinyl]hexyl, 1,1-dimethyl-2-[4-pentyl-(1-, 2- or 3-)piperazinyl]ethyl, [1,2-dimethyl-(3-, 4-, 5- or 6-)piperazinyl]methyl, [1,2,6-trimethyl-(3-, 4- or 5-)piperazinyl]methyl, and 2-[4-(3,4-methylenedioxybenzyl)-(1-, 2- or 3-)piperazinyl]ethyl groups.
Examples of the amidino lower alkyl group which may have a lower alkyl group as a substituent include amidinoalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms and which may have 1 or 2 linear or branched alkyl groups having 1 to 6 carbon atoms such as amidinomethyl, 2-amidinoethyl, 1-amidinoethyl, 3-amidinopropyl, 4-amidinobutyl, 5-amidinopentyl, 6-amidinohexyl, 1,1-dimethyl-2-amidinoethyl, 2-methyl-3-amidinopropyl, N,N-dimethylamidinomethyl, 2-(N,N-dimethylamidino)ethyl, 1-(N-methylamidino)ethyl, 3-(N-ethylamidino)propyl, 4-(N-n-propylamidino)propyl, 5-(N-n-pentylamidino)pentyl, 6-(N-n-hexylamidino)hexyl, and (N-methyl-N-ethylamidino)methyl groups.
Examples of the carbazolyl group which may have a lower alkyl group as a substituent on the carbazole ring include carbazolyl groups which may have 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the carbazole ring such as (1-, 2-, 3- or 4-)carbazolyl, 9-methyl-(1-, 2-, 3- or 4-)carbazolyl, 9-ethyl-(1-, 2-, 3- or 4-)carbazolyl, 1-ethyl-(2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-)carbazolyl, 2-n-propyl-(1-, 3-, 4-, 5-, 6-, 8- or 9-)carbazolyl, 3-n-butyl-(1-, 2-, 4-, 5-, 6-, 7-, 8- or 9-)carbazolyl, 4-n-pentyl-(1-, 2-, 3-, 5-, 6-, 7-, 8- or 9-)carbazolyl, 5-n-hexyl-(1-, 2-, 3-, 4-, 6-, 7-, 8- or 9-)carbazolyl, 6,9-dimethyl-(1-, 2-, 3-, 4-, 5-, 7- or 8-)carbazolyl, and 1,7,8-trityl-(2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-)carbazolyl groups.
Examples of the amidino group which may have a lower alkyl group as a substituent include amidino groups which may have 1 or 2 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents such as amidino, N,N-dimethylamidino, N-methylamidino, N-ethylamidino, N-n-propylamidino, N-n-butylamidino, N-n-pentylamidino, N-n-hexylamidino, N,N-diethylamidino, and N-methyl-N-ethylamidino groups.
Examples of the phenyl lower alkyl group (which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkylenedioxy group and a lower alkoxy group), include, in addition to the above described phenyl lower alkyl groups, phenylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms (and which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a linear or branched alkylenedioxy group having 1 to 4 carbon atoms and a linear or branched alkoxy group having 1 to 6 carbon atoms) such as 3,4-methylenedioxybenzyl, 3,4-trimethylenedioxybenzyl, 2-(2,3-ethylenedioxyphenyl)ethyl, 1-(3,4-trimethylenedioxyphenyl)ethyl, 3-(2,3-tetramethylenedioxyphenyl)propyl, 4-(3,4-methylenedioxyphenyl)butyl, 5-(2,3-ethylenedioxyphenyl)pentyl, 6-(3,4-trimethylenedioxyphenyl)hexyl, 1,1-dimethyl-2-(2,3-methylenedioxyphenyl)ethyl, 2-methyl-3-(3,4-ethylenedioxyphenyl)propyl, 2-methoxybenzyl, 2-(2-methoxyphenyl)ethyl, 2-(3-methoxyphenyl)ethyl, 2-(4-methoxyphenyl)ethyl, 4-methoxybenzyl, 1-(2-ethoxyphenyl)ethyl, 3-(3-ethoxyphenyl)propyl, 4-(4-ethoxyphenyl)butyl, 5-(4-isopropoxyphenyl)pentyl, 6-(3-butoxyphenyl)hexyl, 1,1-dimethyl-2-(4-pentyloxyphenyl)ethyl, 2-methyl-3-(4-hexyloxyphenyl)propyl, 3,4-dimethoxybenzyl, 3,4-diethoxybenzyl, 2,4-dimethoxybenzyl, 2,5-dimethoxybenzyl, 2,6-dimethoxybenzyl, and 3,4,5-trimethoxybenzyl groups.
Examples of the piperazinyl substituted oxalyl group which may have, on the piperazine ring, 1 to 3 substituents selected from the group consisting of a phenyl lower alkyl group (which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkylenedioxy group and a lower alkoxy group) and a pyridyl lower alkyl group include piperazinyl substituted oxalyl groups which may have, on the piperazine ring, 1 to 3 substituents selected from the group consisting of a phenylalkyl group whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms (and which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a linear or branched alkylenedioxy group having 1 to 4 carbon atoms and a linear or branched alkoxy group having 1 to 6 carbon atoms) and a pyridylalkyl group whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as 4-(3,4-methylenedioxybenzyl)-(1-, 2- or 3-)piperazinyloxalyl, 4-(2-, 3- or 4-pyridylmethyl)-(1-, 2- or 3-)piperazinyloxalyl, 4-(3,4-dimethyoxybenzyl)-1-, 2- or 3-)piperazinyloxalyl, 4-(2,3-methylenedioxybenzyl)-(1-, 2- or 3-)piperazinyloxalyl, 4-(3,4-ethylenedioxybenzyl)-(1-, 2- or 3-)piperazinyloxalyl, 4-[2-(2-, 3- or 4-pyridyl)ethyl]-(1-, 2- or 3-)piperazinyloxalyl, 4-[3-(2-, 3- or 4-pyridyl)propyl-(1-, 2- or 3-)piperazinyloxalyl, 2,4-bis(2-, 3- or 4-pyridylmethyl)-(1-, 2- or 3-)piperazinyloxalyl, 2-(3,4-methylenedioxybenzyl)-4-(2-, 3- or 4-pyridylmethyl)-(1-, 2- or 3-)piperazinyloxalyl, and 2,3,4-tri(2-, 3- or 4-pyridylmethyl)-(1-, 2- or 3-)piperazinyloxalyl groups.
Examples of the cyano substituted lower alkyl group include cyanoalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as cyanomethyl, 2-cyanoethyl, 1-cyanoethyl, 3-cyanopropyl, 4-cyanobutyl, 5-cyanopentyl, 6-cyanohexyl, 1,1-dimethyl-2-cyanoethyl, and 2-methyl-3-cyanopropyl groups.
Examples of the 5-to 7-membered saturated heterocyclic ring formed by binding R36 and R37 each other, together with nitrogen atoms bound to them, through or not through a nitrogen atom, an oxygen atom, or a sulfur atom include pyrrolidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, and homopiperazinyl groups.
Examples of the 5-to 10-membered saturated or unsaturated heterocyclic ring formed by binding R14 and R15 each other, together with nitrogen atoms bound to them, through or not through a nitrogen atom, an oxygen atom, or a sulfur atom include 1,2,3,4,5,6-hexahydropyrimidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, homopiperazinyl, homopiperidinyl, thiazolidinyl, 1,2,5,6-tetrahydropyridyl, pyrrolyl, pyrazolyl, imidazolyl, 2-pyrrolinyl, 2-imidazolinyl, imidazolidinyl, 2-pyrazolinyl, pyrazolidinyl, 1,2-dihydropyridyl, 1,2-dihydroquinolyl, 1,2,3,4-tetrahydroquinolyl, 1,2,3,4-tetrahydroisoquinolyl, 1,2-dihydroisoquinolyl, indolyl, isoindolyl, indolinyl, isoindolinyl, 3,4-dihydro-2H-1,4-benzooxazinyl, 3,4-dihydro-2H-1,4-benzothiazolidinyl, 1,4-benzothiazinyl, 1,2,3,4-tetrahydroquinoxalinyl, 1,2,3,4-tetrahydrocinnolinyl, 1,2,3,4-tetrahydrophthalazinyl, 1,2,3,4-tetrahydroquinazolinyl, 1,2-dihydroquinoxalinyl, 3,4-dihydroquinoxalinyl, 1,4-dihydroquinoxalinyl, 1,2-dihydrocinnolinyl, 1,2-dihydrophthalazinyl, 3,4-dihydrophthalazinyl, 1,2-dihydroquinazolinyl, 3,4-dihydroquinazolinyl, indazolyl, indazolinyl, 6-azabicyclo[3,2,1]octyl, 3-aza-spiro[5,5]undecyl, and thiazolidinyl groups. Preferably, R14 and R15, together with the nitrogen atom to which they bind, bind to each other, directly or via a nitrogen atom to form a 6-membered saturated heterocyclic group. Most preferably, they include piperidinyl and piperazinyl groups.
Examples of the phenyl lower alkoxy group include phenylalkoxy groups whose alkoxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms such as benzyloxy, 2-phenylethoxy, 1-phenylethoxy, 3-phenylpropoxy, 4-phenylbutoxy, 5-phenylpentyloxy, 6-phenylhexyloxy, 1,1-dimethyl-2-phenylethoxy, and 2-methyl-3-phenylpropoxy groups.
Examples of the phenyl substituted lower alkyl group which has 1 or 2 phenyl groups which may be substituted on the phenyl ring with 1 to 3 substituents selected from the group consisting of a lower alkanoyl group, an amino group which may have a lower alkanoyl group as a substituent, a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, a phenyl lower alkoxy group, a hydroxyl group, and a lower alkylenedioxy groups; and which may have a pyridyl group on the lower alkyl group include in addition to the above described phenyl lower alkyl groups, phenyl substituted alkyl groups which have 1 or 2 phenyls which may be substituted on the phenyl ring with 1 to 3 substituents selected from the group consisting of a linear or branched alkanoyl group having 1 to 6 carbon atoms, an amino group which may have 1 or 2 linear or branched alkanoyl groups having 1 to 6 carbon atoms as substituents, an alkoxycarbonyl group whose akloxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms, a cyano group, a nitro group, a phenyl group, a halogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, a linear or branched alkoxy group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, a phenylalkoxy groups whose alkoxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms, a hydroxy group, and a linear or branched alkylenedioxy group having 1 to 4 carbon atoms; which may have a pyridyl group on the alkyl group, and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms, such as 1-phenyl-1-(2, 3 or 4-)pyridyl methyl, 1,1-diphenylmethyl, 1,1-di(4-fluorophenyl)methyl, 1-phenyl-1-(4-methoxyphenyl)methyl, 3,4-methylenedioxybenzyl, 3,4-ethylenedioxybenzyl, 3,4-trimethylenedioxybenzyl, 2,5-difluorobenzyl, 2,4-difluorobenzyl, 3,4-difluorobenzyl, 3,5-difluorobenzyl, 2,6-difluorobenzyl, 3-trifluoromethylbenzyl, 2-trifluoromethylbenzyl, 4-trifluoromethylbenzyl, 3,4-dimethoxybenzyl, 3,5-dimethoxybenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 2-methylbenzyl, 3-methylbenzyl, 4-methylbenzyl, 3,4-dimethylbenzyl, 2,3-dimethylbenzyl, 2-methoxybenzyl, 3-methoxybenzyl, 4-cyanobenzyl, 2-cyanobenzyl, 3-cyanobenzyl, 4-methoxybenzyl, 2,3-dichlorobenzyl, 2,4-dichlorobenzyl, 2,5-dichlorobenzyl, 3,4-dichlorobenzyl, 2,6-dichlorobenzyl, 4-fluorobenzyl, 3-fluorobenzyl, 2-fluorobenzyl, 4-nitrobenzyl, 3-nitrobenzyl, 2-nitrobenzyl, 3-trifluoromethoxybenzyl, 4-trifluoromethoxybenzyl, 2-trifluoromethoxybenzyl, 4-methoxycarbonylbenzyl, 3-methoxycarbonylbenzyl, 4-tert-butylbenzyl, 4-ethylbenzyl, 4-isopropylbenzyl, 4-methoxy-3-chlorobenzyl, 2-(4-methoxyphenyl)ethyl, 2-(4-fluorophenyl)ethyl, 2-(4-chlorophenyl)ethyl, 2-(3-methoxyphenyl)ethyl, 2-(4-methylphenyl)ethyl, 4-phenylbenzyl, 3,3-diphenylpropyl, 3-methyl-4-nitrobenzyl, 4-(4-methoxyphenyl)butyl, 2-(4-methylphenyl)ethyl, 4-tert-butoxycarbonylbenzyl, 3-chloro-6-methoxybenzyl, 4-acetylaminobenzyl, 4-nitro-3-methylbenzyl, 4-hydroxybenzyl, 3-hydroxybenzyl, 2-hydroxybenzyl, 4-tert-butyrylbenzyl, 4-benzyloxybenzyl, 4-pivaloylbenzyl, 2-(4-acetylphenyl)ethyl, 1-(3-propionylphenyl)ethyl, 3-(2-butyrylphenyl)propyl, 4-(4-pentanoylphenyl)butyl, 5-(3-hexanoylphenyl)pentyl, 6-(2,4-diacetylphenyl)hexyl, 1,1-dimethyl-2-(2,4,6-triacetylphenyl)ethyl, 2-methyl-3-(3,4-diacetylphenyl)propyl, 2-(4-aminophenyl)ethyl, 1-(3-propionylaminophenyl)ethyl, 3-(2-butyrylaminophenyl)propyl, 4-(4-pentanoylamino)phenylbutyl, 5-(hexanoylaminophenyl)pentyl, 6-(N-acetyl-N-propionylaminophenyl)hexyl, 1,1-dimethyl-2-(3,4-diaminophenyl)ethyl, 2-methyl-3-(3,4,5-triacetylaminophenyl)propyl, 2-(2-ethoxycarbonylphenyl)ethyl, 1-(3-propoxycarbonylphenyl)ethyl, 3-(4-pentyloxycarbonylphenyl)propyl, 4-(3-hexyloxycarbonylphenyl)butyl, 5-(3,4-dimethoxycarbonylphenyl)pentyl, 6-(3,4,5-triethoxycarbonylphenyl)hexyl, 1,1-dimethyl-2-(4-butoxycarbonylphenyl)ethyl, 2-methyl-3-(4-methoxycarbonylphenyl)propyl, 2-(2-cyanophenyl)ethyl, 1-(3-cyanophenyl)ethyl, 3-(4-cyanophenyl)propyl, 4-(2-cyanophenyl)butyl, 5-(3-cyanophenyl)pentyl, 6-(4-cyanophenyl)hexyl, 1,1-dimethyl-2-(2,4-dicyanophenyl)ethyl, 2-methyl-3-(2,4,6-tricyanophenyl)propyl, 2-(2-nitrophenyl)ethyl, 1-(3-nitrophenyl)ethyl, 3-(4-nitrophenyl)propyl, 4-(2-nitrophenyl)butyl, 5-(3-nitrophenyl)pentyl, 6-(4-nitrophenyl)hexyl, 1,1-dimethyl-2-(2,4-dinitrophenyflethyl, 2-methyl-3-(2,4,6-trinitrophenyl)propyl, 2-(2-phenylphenyl)ethyl, 1-(3-phenylphenyl)ethyl, 3-(4-phenylphenyl)propyl, 4-(2-phenylphenyl)butyl, 5-(3-phenylphenyl)pentyl, 6-(4-phenylphenyl)hexyl, 1,1-dimethyl-2-(2,4-diphenylphenyl)ethyl, 2-methyl-3-(2,4,6-triphenylphenyl)propyl, 2-(2-fluorophenyl)ethyl, 1-(3-bromophenyl)ethyl, 3-(4-iodophenyl)propyl, 4-(2-bromophenyl)butyl, 5-(3-chlorophenyl)pentyl, 6-(4-bromophenyl)hexyl, 1,1-dimethyl-2-(2,4-dichlorophenyl)ethyl, 2-methyl-3-(2,4,6-trifluorophenyl)propyl, 2-(2-ethylphenyl)ethyl, 1-(3-propylphenyl)ethyl, 3-(4-butylphenyl)propyl, 4-(2-pentylphenyl)butyl, 5-(3-hexylphenyl)pentyl, 6-(4-trifluoromethylphenyl)hexyl, 1,1-dimethyl-2-(2,4-dimethylphenyl)ethyl, 2-methyl-3-[2,4,6-tri(trifluoromethyl)phenyl]propyl, 2-(2-ethoxyphenyl)ethyl, 1-(3-propoxyphenyl)ethyl, 3-(4-butoxyphenyl)propyl, 4-(2-pentyloxyphenyl)butyl, 5-(3-hexyloxyphenyl)pentyl, 6-(4-trifluoromethoxyphenyl)hexyl, 1,1-dimethyl-2-(2,4-dimethoxyphenyl)ethyl, 2-methyl-3-[2,4,6-tri(trifluoromethoxy)phenyl]propyl, 2-(2-benzyloxyphenyl)ethyl, 1-[3-(2-phenylethoxy)phenyl]ethyl, 3-[4-(3-phenylpropoxy)phenyl]propyl, 4-[2-(4-phenylbutoxy)phenyl]butyl, 5-[3-(5-phenylpentyloxy)phenyl]pentyl, 6-[4-(6-phenylhexyloxy)phenyl]hexyl, 1,1-dimethyl-2-(2,4-dibenzyloxyphenyl)ethyl, 2-methyl-3-(2,4,6-tribenzyloxyphenyl)propyl, 2-(2-hydroxyphenyl)ethyl, 1-(3-hydroxyphenyl)ethyl, 3-(4-hydroxyphenyl)propyl, 4-(2-hydroxyphenyl)butyl, 5-(3-hydroxyphenyl)pentyl, 6-(4-hydroxyphenyl)hexyl, 1,1-dimethyl-2-(2,4-dihydroxyphenyl)ethyl, 2-methyl-3-(2,4,6-trihydroxyphenyl)propyl, 2-(3,4-methylenedioxyphenyl)ethyl, 1-(2,3-ethylenedioxyphenyl)ethyl, 3-(3,4-trimethylenedioxyphenyl)propyl, 4-(3,4-tetramethylenedioxyphenyl)butyl, 5-(3,4-methylenedioxyphenyl)pentyl, 6-(3,4-ethylenedioxyphenyl)hexyl, 1,1-dimethyl-2-(3,4-methylenedioxy)ethyl, and 2-methyl-3-(3,4-methylenedioxyphenyl)propyl groups. Preferably, they include phenyl substituted lower alkyl groups which may be substituted on the phenyl ring with group(s), as substituent(s), selected from the group consisting of a lower alkanoyl group, an amino group which may have a lower alkanoyl group as a substituent, a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, a phenyl lower alkoxy group, a hydroxyl group, and a lower alkylenedioxy groups.
Examples of the pyridyl lower alkyl group which may have, on the pyridine ring, 1 to 3 substituents selected from the group consisting of a hydroxyl group and a lower alkyl group which may have a hydroxyl group as a substituent include, in addition to the above described pyridyl lower alkyl groups, pyridylalkyl groups which may have, on the pyridine ring, 1 to 3 substituents selected from the group consisting of a hydroxy group and a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 hydroxy groups as substituents, and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [2-methyl-(3, 4, 5 or 6-)pyridyl]methyl, [2-methyl-3-hydroxy-5-hydroxy methyl-(4 or 6-)pyridyl]methyl, 2-[3-ethyl-(2, 4, 5 or 6-)pyridyl]ethyl, 1-[4-propyl-(2, 3, 5 or 6-)pyridyl]ethyl, 3-[2-butyl-(3, 4, 5 or 6-)pyridyl]propyl, 4-[3-pentyl-(2, 4, 5 or 6-)pyridyl]butyl, 1,1-dimethyl-2-[4-hexyl-(2, 3, 5 or 6-)pyridyl]ethyl, 5-[2,3-dimethyl-(4, 5 or 6-)pyridyl]pentyl, 6-[2,4,6-trimethyl-(3 or 5-)pyridyl]hexyl, 1-[2-hydroxy-(2, 3, 5 or 6-)pyridyl}isopropyl, 2-methyl-3-[3-hydroxy-(2, 4, 5 or 6-)pyridyl]propyl, [2-hydroxy-(3, 4, 5 or 6-)pyridyl]methyl, 2-[3-hydroxy-(2, 4, 5 or 6-)pyridyl]ethyl, 1-[4-hydroxy-(2, 3, 5 or 6-)pyridyl]ethyl, 3-[2-hydroxy-(3, 4, 5 or 6-)pyridyl]propyl, 4-[3-hydroxy-(2, 4, 5 or 6-)pyridyl]butyl, 1,1-dimethyl-2-[4-hydroxy-(2, 3, 5 or 6-)pyridyl]ethyl, 5-[2,3-dihydroxy-(4, 5 or 6-)pyridyl]pentyl, 6-[2,4,6-trihydroxy-(3 or 5-)pyridyl]hexyl, [2-hydroxymethyl-(3, 4, 5 or 6-)pyridyl]methyl, 2-[3-(2-hydroxyethyl)-(2, 4, 5 or 6-)pyridyl]ethyl, 1-[4-(3-hydroxypropyl)-(2, 3, 5 or 6-)pyridyl]ethyl, 3-[2-(4-hydroxybutyl)-(3, 4, 5 or 6-)pyridyl]propyl, 4-[3-(5-hydroxypentyl)-(2, 4, 5 or 6-)pyridyl]butyl, 1,1-dimethyl-2-[4-(6-hydroxyhexyl)-(2, 3, 5 or 6-)pyridyl]ethyl, 5-[2,3-di(hydroxymethyl)-(4, 5 or 6-)pyridyl]pentyl, 6-[2,4,6-tri(hydroxymethyl)-(3 or 5-)pyridyl]hexyl, 1-[2-hydroxymethyl-(2, 3, 5 or 6-)pyridyl]isopropyl, 2-methyl-3-[3-(2,3-dihydroxypropyl)-(2, 4, 5 or 6-)pyridyl]propyl, [2-methyl-3-(2,2,4-trihydroxybutyl)-(4, 5 or 6-)pyridyl]methyl, and [2-methyl-5-hydroxymethyl-(3, 4 or 6-)pyridyl]methyl groups.
Examples of the pyrrolyl lower alkyl group which may have 1 to 3 lower alkyl groups as substituents on the pyrrole ring include pyrrolylalkyl groups which may have 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms on the pyrrole ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(1, 2 or 3-)pyrrolyl]methyl, 2-[(1, 2 or 3-)pyrrolyl]ethyl, 1-[(1, 2 or 3-)pyrrolyl]ethyl, 3-[(1, 2 or 3-)pyrrolyl]propyl, 4-[(1, 2 or 3-)pyrrolyl]butyl, 5-[(1, 2 or 3-)pyrrolyl]pentyl, 6-[(1, 2 or 3-)pyrrolyl]hexyl, 1,1-dimethyl-2-[(1, 2 or 3-)pyrrolyl]ethyl, 2-methyl-3-[(1, 2 or 3-)pyrrolyl]propyl, [1-methyl-(2 or 3-)pyrrolyl]methyl, 2-[2-ethyl-(1, 3, 4 or 5-)pyrrolyl]ethyl, 1-[3-propyl-(1, 2, 4 or 5-)pyrrolyl]ethyl, 3-[1-butyl-(2, 3 or 4-)pyrrolyl]propyl, 4-[2-pentyl-(1, 3, 4 or 5-)pyrrolyl]butyl, 5-[3-hexyl-(1, 2, 4 or 5-)pyrrolyl]pentyl, 6-[1,2-dimethyl-(3, 4 or 5-)pyrrolyl]hexyl, 1,1-dimethyl-2-[1,2,3-trimethyl-(4 or 5-)pyrrolyl]ethyl, and 2-methyl-3-[1-ethyl-2-methyl-(3, 4 or 5-)pyrrolyl]propyl groups.
Examples of the benzoxazolyl lower alkyl group include benzoxazolylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(2, 4, 5, 6 or 7-)benzooxazolyl]methyl, 2-[(2, 4, 5, 6 or 7-)benzooxazolyl]ethyl, 1-[(2, 4, 5, 6 or 7-)benzooxazolyl]ethyl, 3-[(2, 4, 5, 6 or 7-)benzooxazolyl]propyl, 4-[(2, 4, 5, 6 or 7-)benzooxazolyl]butyl, 5-[(2, 4, 5, 6 or 7-)benzooxazolyl]pentyl, 6-[(2, 4, 5, 6 or 7-)benzooxazolyl]hexyl, 1,1-dimethyl-2-[(2, 4, 5, 6 or 7-)benzooxazolyl]ethyl, and 2-methyl-3-[(2, 4, 5, 6 or 7-)benzooxazolyl]propyl groups. Examples of the benzothiazolyl lower alkyl group include benzothiazolylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(2, 4, 5, 6 or 7-)benzothiazolyl]methyl, 2-[(2, 4, 5, 6 or 7-)benzothiazolyl]ethyl, 1-[(2, 4, 5, 6 or 7-)benzothiazolyl]ethyl, 3-[(2, 4, 5, 6 or 7-)benzothiazolyl]propyl, 4-[(2, 4, 5, 6 or 7-)benzothiazolyl]butyl, 5-[(2, 4, 5, 6 or 7-)benzothiazolyl]pentyl, 6-[(2, 4, 5, 6 or 7-)benzothiazolyl]hexyl, 1,1-dimethyl-2-[(2, 4, 5, 6 or 7-)benzothiazolyl]ethyl, and 2-methyl-3-[(2, 4, 5, 6 or 7-)benzothiazolyl]propyl groups.
Examples of the furyl lower alkyl group include furylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(2 or 3-)furyl]methyl, 2-[(2 or 3-)furyl]ethyl, 1-[(2 or 3-)furyl]ethyl, 3-[(2 or 3-)furyl]propyl, 4-[(2 or 3-)furyl]butyl, 5-[(2 or 3-)furyl]pentyl, 6-[(2 or 3-)furyl]hexyl, 1,1-dimethyl-2-[(2 or 3-)furyl]ethyl, and 2-methyl-3-[(2 or 3-)furyl]propyl groups.
Examples of the thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring include thiazolidinylalkyl groups which may have 1 to 3 oxo groups as substituents on the thiazolidine ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2, 3, 4 or 5-)thiazolidinylmethyl, 2-[(2, 3, 4 or 5-)thiazolidinyl]ethyl, 1-[(2, 3, 4 or 5-)thiazolidinyl]ethyl, 3-[(2, 3, 4 or 5-)thiazolidinyl]propyl, 4-[(2, 3, 4 or 5-)thiazolidinyl]butyl, 5-[(2, 3, 4 or 5-)thiazolidinyl]pentyl, 6-[(2, 3, 4 or 5-)thiazolidinyl]hexyl, 1,1-dimethyl-2-[(2, 3, 4 or 5-)thiazolidinyl]ethyl, 2-methyl-3-[(2, 3, 4 or 5-)thiazolidinyl]propyl, [2,4-dioxo-(3 or 5-)thiazolidinyl]methyl, 2-[2-oxo-(3, 4 or 5-)thiazolidinyl]ethyl, 1-[4-oxo-(2, 3 or 5-)thiazolidinyl]ethyl, 3-[2-oxo-(3, 4 or 5-)thiazolidinyl]propyl, 4-[5-oxo-(2, 3 or 4-)thiazolidinyl]butyl, 5-[2,5-dioxo-(3 or 4-)thiazolidinyl]pentyl, 6-[2,4,5-trioxo-3-thiazolidinyl]hexyl, 1-[4,5-dioxo-(2 or 3-)thiazolidinyl]ethyl, 2-[4,5-dioxo-(2- or 3-)thiazolidinyl]ethyl, 1,1-dimethyl-2-[2,4-dioxo-(3 or 5-)thiazolidinyl]ethyl, and 2-methyl-3-[2,4-dioxo-(3 or 5-)thiazolidinyl]propyl groups.
Examples of the thiazolidinylidene lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring include thiazolidinylidenealkyl groups which may have 1 to 3 oxo groups as substituents on the thiazolidine ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2, 4 or 5-)thiazolidinylidenemethyl, (2, 4 or 5-)thiazolidinylideneethyl, (2, 4 or 5-)thiazolidinylidenepropyl, (2, 4 or 5-)thiazolidinylideneisopropyl, (2, 4 or 5-)thiazolidinylidenebutyl, (2, 4 or 5-)thiazolidinylidenepentyl, (2, 4 or 5-)thiazolidinylidenehexyl, 4,5-dioxo-2-thiazolidinylidenemethyl, 2,5-dioxo-4-thiazolidinylidenemethyl, 2,4-dioxo-5-thiazolidinylidenemethyl, 4-oxo-(2 or 5-)thiazolidinylideneethyl, 5-oxo-(2 or 4-)thiazolidinylidenepropyl, and 2-oxo-(4 or 5-)thiazolidinylidenebutyl groups.
Examples of the benzoyl group which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a cyano group, an amino group which may have a lower alkylsulfonyl group as a substituent, a halogen atom, a lower alkoxy group, a lower alkyl group which may have a halogen atom as a substituent, a thiazolidinyl lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, a thiazolidinylidene lower alkyl group which may have an oxo group as a substituent on the thiazolidine ring, and a lower alkylenedioxy group include benzoyl groups which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a cyano group; an amino group which may have 1 or 2 linear or branched alkylsulfonyl groups having 1 to 6 carbon atoms as substituents; a halogen atom; a linear or branched alkoxy group having 1 to 6 carbon atoms; a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents; a thiazolidinylalkyl group which may have 1 to 3 oxo groups as substituents on the thiazolidine ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms; a thiazolidinylidenealkyl group which may have 1 to 3 oxo groups as substituents on the thiazolidine ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms; and a linear or branched alkylenedioxy group having 1 to 4 carbon atoms such as benzoyl, 4-cyanobenzoyl, 3,4-methylenedioxybenzoyl, 2-aminobenzoyl, 3-aminobenzoyl, 4-aminobenzoyl, 3,4-diaminobenzoyl, 2,4,6-triaminobenzoyl, 4-methoxybenzoyl, 4-trifluoromethylbenzoyl, 4-chlorobenzoyl, 3,4-difluorobenzoyl, 2-fluorobenzoyl, 3-bromobenzoyl, 4-iodobenzoyl, 3,4-dimethoxybenzoyl, 4-fluorobenzoyl, 3-cyanobenzoyl, 2-cyanobenzoyl, 2,3-dicyanobenzoyl, 3,4,5-tricyanobenzoyl, 4-methylbenzoyl, 4-(2,4-dioxothiazolidinylmethyl)benzoyl, 4-(2,4-dioxothiazolidinylidenemethyl)benzoyl, 2-methylbenzoyl, 3-methylbenzoyl, 2-ethylbenzoyl, 3-ethylbenzoyl, 4-ethylbenzoyl, 4-isopropylbenzoyl, 3-butylbenzoyl, 4-pentylbenzoyl, 4-hexylbenzoyl, 3,4-dimethylbenzoyl, 3,4-diethylbenzoyl, 2,4-dimethylbenzoyl, 2,5-dimethylbenzoyl, 2,6-dimethylbenzoyl, 3,4,5-trimethylbenzoyl, 2-methoxybenzoyl, 3-methoxybenzoyl, 2-ethoxybenzoyl, 3-ethoxybenzoyl, 4-ethoxybenzoyl, 4-isopropoxybenzoyl, 3-butoxybenzoyl, 4-pentyloxybenzoyl, 4-hexyloxybenzoyl, 3,4-diethoxybenzoyl, 2,4-dimethoxybenzoyl, 2,5-dimethoxybenzoyl, 2,6-dimethoxybenzoyl, 3,4,5-trimethoxybenzoyl, 2-trifluoromethylbenzoyl, 3-trifluoromethylbenzoyl, 4-trifluoromethylbenzoyl, 2-(bromomethyl)benzoyl, 3-(2-chloroethyl)benzoyl, 4-(2,3-dichloropropyl)benzoyl, 4-(4-fluorobutyl)benzoyl, 3-(5-chloropentyl)benzoyl, 4-(5-bromohexyl)benzoyl, 4-(5,6-dibromohexyl)benzoyl, 3,4-di(trifluoromethyl)benzoyl, 3,4-di(4,4,4-trichlorobutyl)benzoyl, 2,4-di(3-chloro-2-methylpropyl)benzoyl, 2,5-di(3-chloropropyl)benzoyl, 2,6-di(2,2,2-trifluoroethyl)benzoyl, 3,4,5-tri(trifluoromethyl)benzoyl, 4-(2,2,2-trichloroethyl)benzoyl, 2-methyl-4-trifluoromethylbenzoyl, 3-ethyl-4-trichloromethylbenzoyl, 2-methoxy-4-trifluoromethylbenzoyl, 3-ethyl-4-fluorobenzoyl, 3-ethoxy-4-trichloromethylbenzoyl, 2-methyl-3-trifluoromethyl-4-trifluoromethylbenzoyl, 3-fluorobenzoyl, 4-fluorobenzoyl, 2-bromobenzoyl, 4-bromobenzoyl, 2-iodobenzoyl, 3-iodobenzoyl, 2,3-dibromobenzoyl, 2,4-diiodobenzoyl, 2,5-difluorobenzoyl, 2,6-dichlorobenzoyl, 2,4,6-trichlorobenzoyl, 2,4-difluorobenzoyl, 3,4-difluorobenzoyl, 3,5-difluorobenzoyl, 2,6-difluorobenzoyl, 2-chlorobenzoyl, 3-chlorobenzoyl, 4-chlorobenzoyl, 2,3-dichlorobenzoyl, 2,4-dichlorobenzoyl, 2,5-dichlorobenzoyl, 3,4-dichlorobenzoyl, 2,6-dichlorobenzoyl, 3,5-dichlorobenzoyl, 2,4,6-trifluorobenzoyl, 2,4-difluorobenzoyl, 3,4-difluorobenzoyl, 3,4-methylenedioxybenzoyl, 3,4-trimethylenedioxybenzoyl, 2,3-ethylenedioxybenzoyl, 3,4-trimethylenedioxybenzoyl, 2,3-tetramethylenedioxybenzoyl, 2,3-methylenedioxybenzoyl, 3,4-ethylenedioxybenzoyl, and 2-methanesulfonylaminobenzoyl groups.
Examples of the thiazolidinyl lower alkanoyl group which may be substituted on the thiazolidine ring with a group selected from the group consisting of an oxo group and a group of the formula:
wherein Ra and Rb each represent a lower alkyl group, include thiazolidinylalkanoyl groups which may be substituted on the thiazolidine ring with 1 to 3 substituents selected from the group consisting of an oxo group and a group of the formula:
wherein Ra and Rb each represent a linear or branched alkyl group having 1 to 6 carbon atoms, and whose alkanoyl moiety is a linear or branched alkanoyl group having 2 to 6 carbon atoms such as 2-[(2, 3, 4 or 5-)thiazolidinyl]acetyl, 3-[(2, 3, 4 or 5-)thiazolidinyl]propionyl, 2-[(2, 3, 4 or 5-)thiazolidinyl]propionyl, 4-[(2, 3, 4 or 5-)thiazolidinyl]butyryl, 5-[(2, 3, 4 or 5-)thiazolidinyl]pentanoyl, 6-[(2, 3, 4 or 5-)thiazolidinyl]hexanoyl, 2,2-dimethyl-3-[(2, 3, 4 or 5-)thiazolidinyl]propionyl, 2-methyl-3-[(2, 3, 4 or 5-)thiazolidinyl]propionyl, [2,4-dioxo-(3 or 5-)thiazolidinyl]acetyl, 3-[2-oxo-(3, 4 or 5-)thiazolidinyl]propionyl, 2-[4-oxo-(2, 3 or 5-)thiazolidinyl]propionyl, 4-[5-oxo-(2, 3 or 4-)thiazolidinyl]butyryl, 5-[2,5-dioxo-(3 or 4-)thiazolidinyl]pentanoyl, 6-[2,4,5-trioxo-3-thiazolidinyl]hexanoyl, 2-[4,5-dioxo-(2 or 3-)thiazolidinyl]acetyl, 2,2-dimethyl-3-[2,4-dioxo-(3 or 5-)thiazolidinyl]propionyl, 2-methyl-3-[2,4-dioxo-(3 or 5-)thiazolidinyl]propionyl, 2-[4-oxo-2-isopropylidenehydrazono-(3 or 5-)thiazolidinyl]acetyl, 2-[2-oxo-5-isopropylidenehydrazono-(3 or 4-)thiazolidinyl]acetyl, 2-[2,4-di(isopropylidenehydrazono)-(3 or 5-)thiazolidinyl]acetyl, 3-[2-methylidenehydrazono-(3, 4 or 5-)thiazolidinyl]propionyl, 2-[4-ethylidenehydrazono-(2, 3 or 5-)thiazolidinyl]propionyl, 4-[5-propylidenehydrazono-(2, 3 or 4-)thiazolidinyl]butyryl, 5-[2,5-di(isopropylidenehydrazono)-(3 or 4-)thiazolidinyl]pentanoyl, 6-[2,4,5-tri(isopropylidenehydrazono)-3-thiazolidinyl]hexanoyl, 2-[4,5-di(isopropylidenehydrazono)-(2 or 3-)thiazolidinyl]acetyl, 2,2-dimethyl-3-[4-butylidenehydrazono(2, 3 or 5-)thiazolidinyl]propionyl, 2-methyl-3-[5-pentylidene-(2, 3 or 4-)thiazolidinyl]propionyl, and 2-(hexylidenehydrazono)-(3, 4 or 5-)thiazolidinylacetyl groups.
Examples of the lower alkyl group which may have a substituent selected from the group consisting of a hydroxyl group and a halogen atom include, in addition to the above described lower alkyl groups, linear or branched alkyl groups having 1 to 6 carbon atoms which may have 1 to 3 substituents selected from the group consisting of a hydroxy group and a halogen atom such as hydroxymethyl, 2-hydroxyethyl, 1-hydroxyethyl, 3-hydroxypropyl, 2,3-dihydroxypropyl, 4-hydroxybutyl, 1,1-dimethyl-2-hydroxyethyl, 5,5,4-trihydroxypentyl, 5-hydroxypentyl, 6-hydroxyhexyl, 1-hydroxyisopropyl, 2-methyl-3-hydroxypropyl, trifluoromethyl, trichloromethyl, chloromethyl, bromomethyl, fluoromethyl, iodomethyl, difluoromethyl, dibromomethyl, 2-chloroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 3-chloropropyl, 2,3-dichloropropyl, 4,4,4-trichlorobutyl, 4-fluorobutyl, 5-chloropentyl, 3-chloro-2-methylpropyl, 5-bromohexyl, 5,6-dibromohexyl, 2-hydroxy-3-fluoropropyl, and 2,2-dichloro-3-hydroxybutyl groups.
Examples of the carbamoyl group which may have a group selected from the group consisting of a lower alkoxy lower alkyl group and a lower alkyl group include carbamoyl groups which may have 1 or 2 groups selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms and which has a linear or branched alkoxy group having 1 to 6 carbon atoms and a linear or branched alkyl group having 1 to 6 carbon atoms such as carbamoyl, N-(2-methoxyethyl)carbamoyl, methylcarbamoyl, ethylcarbamoyl, propylcarbamoyl, isopropylcarbamoyl, butylcarbamoyl, tert-butylcarbamoyl, pentylcarbamoyl, hexylcarbamoyl, dimethylcarbamoyl, diethylcarbamoyl, dipropylcarbamoyl, dibutylcarbamoyl, dipentylcarbamoyl, dihexylcarbamoyl, N-methyl-N-ethylcarbamoyl, N-ethyl-N-propylcarbamoyl, N-methyl-N-butylcarbamoyl, N-methyl-N-hexylcarbamoyl, N-(methoxymethyl)carbamoyl, N-(3-propoxypropyl)carbamoyl, N-(4-butoxybutyl)carbamoyl, N-(4-ethoxybutyl)carbamoyl, N-(5-pentyloxypentyl)carbamoyl, N-(5-methoxypentyl)carbamoyl, N-(6-hexyloxyhexyl)carbamoyl, di(2-methoxyethyl)carbamoyl, N-(2-methoxyethyl)-N-methylcarbamoyl, and N-(2-methoxyethyl)-N-ethylcarbamoyl groups.
Examples of the phenyl group which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a carbamoyl group which may have a group selected from the group consisting of a lower alkoxy lower alkyl group and a lower alkyl group, a lower alkoxycarbonyl group, a carboxy group, a cyano group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, a benzoyl group which may have a halogen atom as a substituent on the phenyl ring, a phenyl lower alkyl group which may have a halogen atom as a substituent on the phenyl ring, and a hydroxyl group include phenyl groups which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a carbamoyl group which may have 1 or 2 groups selected from the group consisting of an alkoxyalkyl group whose alkoxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms and a linear or branched alkyl group having 1 to 6 carbon atoms; an alkoxycarbonyl group whose akloxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms; a carboxy group; a cyano group; a phenyl group;
a halogen atom; a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents; a linear or branched alkoxy group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents; a benzoyl group which may have 1 to 3 halogen atoms as substituents on the phenyl ring; a phenylalkyl group which may have 1 to 3 halogen atoms as substituents on the phenyl ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms, and a hydroxyl group such as phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-butylphenyl, 4-pentylphenyl, 4-hexylphenyl, 3,4-dimethylphenyl, 3,4-diethylphenyl, 2,4-dimethylphenyl, 2,3-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4,5-trimethylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 4-isopropoxyphenyl, 3-butoxyphenyl, 4-pentyloxyphenyl, 4-hexyloxyphenyl, 3,4-dimethoxyphenyl, 3,4-diethoxyphenyl, 2,4-dimethoxyphenyl, 2,5-dimethoxyphenyl, 2,6-dimethoxyphenyl, 3,4,5-trimethoxyphenyl, 2-trifluoromethoxyphenyl, 3-trifluoromethoxyphenyl, 4-trifluoromethoxyphenyl, 2-(bromomethoxy)phenyl, 3-(2-chloroethoxy)phenyl, 4-(2,3-dichloropropoxy)phenyl, 4-(4-fluorobutoxy)phenyl, 3-(5-chloropentyloxy)phenyl, 4-(5-bromohexyloxy)phenyl, 4-(5,6-dibromohexyloxy)phenyl, 3,4-di(trifluoromethoxy)phenyl, 3,4-di(4,4,4-trichlorobutoxy)phenyl, 2,4-di(3-chloro-2-methoxypropyl)phenyl, 2,5-di(3-chloropropoxy)phenyl, 2,6-di(2,2,2-trifluoroethoxy)phenyl, 3,4,5-tri(trifluoromethoxy)phenyl, 4-(2,2,2-trichloroethoxy)phenyl, 2-methyl-4-trifluoromethoxyphenyl, 3-ethyl-4-trichloromethoxyphenyl, 2-methoxy-4-trifluoromethoxyphenyl, 3-ethoxy-4-trichloromethoxyphenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2-(bromomethyl)phenyl, 3-(2-chloroethyl)phenyl, 4-(2,3-dichloropropyl)phenyl, 4-(4-fluorobutyl)phenyl, 3-(5-chloropentyl)phenyl, 4-(5-bromohexyl)phenyl, 4-(5,6-dibromohexyl)phenyl, 3,4-di(trifluoromethyl)phenyl, 3,4-di(4,4,4-trichlorobutyl)phenyl, 2,4-di(3-chloro-2-methylpropyl)phenyl, 2,5-di(3-chloropropyl)phenyl, 2,6-di(2,2,2-trifluoroethyl)phenyl, 3,4,5-tri(trifluoromethyl)phenyl, 4-(2,2,2-trichloroethyl)phenyl, 2-methyl-4-trifluoromethylphenyl, 3-ethyl-4-trichloromethylphenyl, 2-methoxycarbonylphenyl, 3-methoxycarbonylphenyl, 4-methoxycarbonylphenyl, 2-ethoxycarbonylphenyl, 3-ethoxycarbonylphenyl, 4-ethoxycarbonylphenyl, 4-isopropoxycarbonylphenyl, 3-butoxycarbonylphenyl, 4-tert-butoxycarbonylphenyl, 4-pentyloxycarbonylphenyl, 4-hexyloxycarbonylphenyl, 3,4-dimethoxycarbonylphenyl, 3,4-diethoxycarbonylphenyl, 2,4-dimethoxycarbonylphenyl, 2,5-diethoxycarbonylphenyl, 2,6-dimethoxycarbonylphenyl, 3,4,5-triethoxycarbonylphenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, 3,4-dicyanophenyl, 3,5-dicyanophenyl, 2,4-dicyanophenyl, 2,5-dicyanophenyl, 2,6-dicyanophenyl, 3,4,5-tricyanophenyl, 2-phenylphenyl, 3-phenylphenyl, 4-phenylphenyl, 3,4-diphenylphenyl, 3,5-diphenylphenyl, 2,4-diphenylphenyl, 2,5-diphenylphenyl, 2,6-diphenylphenyl, 3,4,5-triphenylphenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 2,5-dichlorophenyl, 3,4-dichlorophenyl, 2,6-dichlorophenyl, 3,5-dichlorophenyl, 2,4,6-trichlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2,5-difluorophenyl, 2,4-difluorophenyl, 3,4-difluorophenyl, 3,5-difluorophenyl, 2,6-difluorophenyl, 2,4,6-trifluorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2-iodophenyl, 3-iodophenyl, 4-iodophenyl, 2,3-dibromophenyl, 2,4-diiodophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 4-hydroxyphenyl, 3,4-dihydroxyphenyl, 3,5-dihydroxyphenyl, 2,4-dihydroxyphenyl, 2,5-dihydroxyphenyl, 2,6-dihydroxyphenyl, 3,4,5-trihydroxyphenyl, 3-benzylphenyl, 2-(2-phenylethyl)phenyl, 4-(1-phenylethyl)phenyl, 2-(3-phenylpropyl)phenyl, 3-(4-phenylbutyl)phenyl, 4-(5-phenylpentyl)phenyl, 2-(6-phenylhexyl)phenyl, 4-(1,1-dimethyl-2-phenylethyl)phenyl, 3-(2-methyl-3-phenylpropyl)phenyl, 2-(4-fluorobenzyl)phenyl, 2-methyl-5-chlorophenyl, 2-methoxy-5-chlorophenyl, 4-(4-fluorobenzoyl)phenyl, 4-(4-fluorobenzyl)phenyl, 3-(2-chlorobenzyl)phenyl, 4-(3-chlorobenzyl)phenyl, 2-(4-chlorobenzyl)phenyl, 3-[2-(4-fluorophenyl)ethyl]phenyl, 4-[2-(4-chlorophenyl)ethyl]phenyl, 2-(3,4-dibromobenzyl)phenyl, 3-(3,4-diiodobenzyl)phenyl, 4-(2,4-difluorobenzyl)phenyl, 2-(2,5-dichlorobenzyl)phenyl, 3-(2,6-dichlorobenzyl)phenyl, 4-(3,4,5-trifluorobenzyl)phenyl, 2-[3-(4-chlorophenyl)propyl]phenyl, 3-[1-(2-bromophenyl)ethyl]phenyl, 4-[4-(3-fluorophenyl)butyl]phenyl, 2-[5-(4-iodophenyl)pentyl]phenyl, 3-[6-(4-chlorophenyl)hexyl]phenyl, 2-[1,1-dimethyl-2-(3-fluorophenyl)ethyl]phenyl, 4-[2-methyl-3-(4-chlorophenyl)propyl]phenyl, 2,4-dibenzylphenyl, 2,4,6-tribenzylphenyl, 2-chloro-4-cyanophenyl, 3-hydroxy-4-phenylphenyl, 3-ethoxycarbonyl-2-benzoylphenyl, 2-benzyl-4-methyl-6-methoxyphenyl, 4-[(2-methoxyethyl)carbamoyl]phenyl, 3-(N-ethyl-N-isopropylcarbamoyl)phenyl, 4-dimethylcarbamoylphenyl, 2-carboxyphenyl, 3-carboxyphenyl, and 4-carboxyphenyl groups.
Examples of the phenyl group which has a lower alkylenedioxy group as a substituent on the phenyl ring include phenyl groups which has a linear or branched alkylenedioxy group having 1 to 4 carbon atom as a substituent on the phenyl ring such as 3,4-methylenedioxyphenyl, 3,4-trimethylenedioxyphenyl, 2,3-ethylenedioxyphenyl, 2,3-tetramethylenedioxyphenyl, 2,3-methylenedioxyphenyl, 3,4-ethylenedioxyphenyl, and 2,3-trimethylenedioxyphenyl groups.
Examples of the naphthyl lower alkyl group include naphthylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1 or 2-)naphthylmethyl, 2-[(1 or 2-)naphthyl]ethyl, 1-[(1 or 2-)naphthyl]ethyl, 3-[(1 or 2-)naphthyl]propyl, 4-[(1 or 2-)naphthyl]butyl, 5-[(1 or 2-)naphthyl]pentyl, 6-[(1 or 2-)naphthyl]hexyl, 1,1-dimethyl-2-[(1 or 2-)naphthyl]ethyl, and 2-methyl-3-[(1 or 2-)naphthyl]propyl groups.
Examples of the phenoxy group which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a cyano group, a lower alkyl group which may have a halogen atom as a substituent, and a lower alkoxy group which may have a halogen atom as a substituent include phenoxy groups which may be substituted on the phenyl group with 1 to 3 groups selected from the group consisting of a cyano group, a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, and a linear or branched alkoxy group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents such as phenoxy, 2-methylphenoxy, 3-methylphenyl, 4-methylphenoxy, 2-ethylphenoxy, 3-ethylphenoxy, 4-ethylphenoxy, 4-isopropylphenoxy, 3-butylphenoxy, 4-pentylphenoxy, 4-hexylphenoxy, 3,4-dimethylphenoxy, 3,4-diethylphenoxy, 2,4-dimethylphenoxy, 2,5-dimethylphenoxy, 2,6-dimethylphenoxy, 3,4,5-trimethylphenoxy, 2-methoxyphenoxy, 3-methoxyphenoxy, 4-methoxyphenoxy, 2-ethoxyphenoxy, 3-ethoxyphenoxy, 4-ethoxyphenoxy, 4-isopropoxyphenoxy, 3-butoxyphenoxy, 4-pentyloxyphenoxy, 4-hexyloxyphenoxy, 3,4-dimethoxyphenoxy, 3,4-diethoxyphenoxy, 2,4-dimethoxyphenoxy, 2,5-dimethoxyphenoxy, 2,6-dimethoxyphenoxy, 3,4,5-trimethoxyphenoxy, 2-trifluoromethoxyphenoxy, 3-trifluoromethoxyphenoxy, 4-trifluoromethoxyphenoxy, 2-(bromomethoxy)phenoxy, 3-(2-chloroethoxy)phenoxy, 4-(2,3-dichloropropoxy)phenoxy, 4-(4-fluorobutoxy)phenoxy, 3-(5-chloropentyloxy)phenoxy, 4-(5-bromohexyloxy)phenoxy, 4-(5,6-dibromohexyloxy)phenoxy, 3,4-di(trifluoromethoxy)phenoxy, 3,4-di(4,4,4-trichlorobutoxy)phenoxy, 2,4-di(3-chloro-2-methoxypropyl)phenoxy, 2,5-di(3-chloropropoxy)phenoxy, 2,6-di(2,2,2-trifluoroethoxy)phenoxy, 3,4,5-tri(trifluoromethoxy)phenoxy, 4-(2,2,2-trichloroethoxy)phenoxy, 2-methyl-4-trifluoromethoxyphenoxy, 3-ethyl-4-trichloromethoxyphenoxy, 2-methoxy-4-trifluoromethoxyphenoxy, 3-ethoxy-4-trichloromethoxyphenoxy, 2-trifluoromethylphenoxy, 3-trifluoromethylphenoxy, 4-trifluoromethylphenoxy, 2-(bromomethyl)phenoxy, 3-(2-chloroethyl)phenoxy, 4-(2,3-dichloropropyl)phenoxy, 4-(4-fluorobutyl)phenoxy, 3-(5-chloropentyl)phenoxy, 4-(5-bromohexyl)phenoxy, 4-(5,6-dibromohexyl)phenoxy, 3,4-di(trifluoromethyl)phenoxy, 3,4-di(4,4,4-trichlorobutyl)phenoxy, 2,4-di(3-chloro-2-methylpropyl)phenoxy, 2,5-di(3-chloropropyl)phenoxy, 2,6-di(2,2,2-trifluoroethyl)phenoxy, 3,4,5-tri(trifluoromethyl)phenoxy, 4-(2,2,2-trichloroethyl)phenoxy, 2-methyl-4-trifluoromethylphenoxy, 3-ethyl-4-trichloromethylphenoxy, 2-cyanophenoxy, 3-cyanophenoxy, 4-cyanophenoxy, 3,4-dicyanophenoxy, 3,5-dicyanophenoxy, 2,3-dicyanophenoxy, 2,4-dicyanophenoxy, 2,5-dicyanophenoxy, 2,6-dicyanophenoxy, 3,4,5-tricyanophenoxy, 2-cyano-4-methylphenoxy, 3-cyano-4-methoxyphenoxy, 3-cyano-5-trifluoromethylphenoxy, and 4-cyano-3-trifluoromethoxyphenoxy groups.
Examples of the phenyl lower alkoxy group which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, and a lower alkoxy group which may have a halogen atom as a substituent include, in addition to the above described phenyl lower alkoxy groups, phenylalkoxy groups which may be substituted on the phenyl ring with 1 to 3 groups selected from the group consisting of a halogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, and a linear or branched alkoxy group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, and whose alkoxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms such as 2,5-difluorobenzyloxy, 2,4-difluorobenzyloxy, 3,4-difluorobenzyloxy, 3,5-difluorobenzyloxy, 2,6-difluorobenzyloxy, 3-trifluoromethylbenzyloxy, 2-trifluoromethylbenzyloxy, 4-trifluoromethylbenzyloxy, 3,4-dimethoxybenzyloxy, 3,5-dimethoxybenzyloxy, 2-chlorobenzyloxy, 3-chlorobenzyloxy, 4-chlorobenzyloxy, 2-methylbenzyloxy, 3-methylbenzyloxy, 4-methylbenzyloxy, 3,4-dimethylbenzyloxy, 2,3-dimethylbenzyloxy, 2-methoxybenzyloxy, 3-methoxybenzyloxy, 4-methoxybenzyloxy, 2,3-dichlorobenzyloxy, 2,4-dichlorobenzyloxy, 2,5-dichlorobenzyloxy, 3,4-dichlorobenzyloxy, 2,6-dichlorobenzyloxy, 4-fluorobenzyloxy, 3-fluorobenzyloxy, 2-fluorobenzyloxy, 3-trifluoromethoxybenzyloxy, 4-trifluoromethoxybenzyloxy, 2-trifluoromethoxybenzyloxy, 4-tert-butylbenzyloxy, 4-ethylbenzyloxy, 4-isopropylbenzyloxy, 4-methoxy-3-chlorobenzyloxy, 2-(4-methoxyphenyl)ethoxy, 2-(4-fluorophenyl)ethoxy, 2-(4-chlorophenyl)ethoxy, 2-(3-methoxyphenyl)ethoxy, 2-(4-methylphenyl)ethoxy, 3-methyl-4-chlorobenzyloxy, 4-(4-methoxyphenyl)butoxy, 2-(4-methylphenyl)ethoxy, 4-tert-butoxybenzyloxy, 3-chloro-6-methoxybenzyloxy, 4-methoxy-3-methylbenzyloxy, 2-(2-fluorophenyl)ethoxy, 1-(3-bromophenyl)ethoxy, 3-(4-iodophenyl)propoxy, 4-(2-bromophenyl)butoxy, 5-(3-chlorophenyl)pentyloxy, 6-(4-bromophenyl)hexyloxy, 1,1-dimethyl-2-(2,4-dichlorophenyl)ethoxy, 2-methyl-3-(2,4,6-trifluorophenyl)propoxy, 2-(2-ethylphenyl)ethoxy, 1-(3-propylphenyl)ethoxy, 3-(4-butylphenyl)propoxy, 4-(2-pentylphenyl)butoxy, 5-(3-hexylphenyl)pentyloxy, 6-(4-trifluoromethylphenyl)hexyloxy, 1,1-dimethyl-2-(2,4-dimethylphenyl)ethoxy, 2-methyl-3-[2,4,6-tri(trifluoromethyl)phenyl]propoxy, 2-(2-ethoxyphenyl)ethoxy, 1-(3-propoxyphenyl)ethoxy, 3-(4-butoxyphenyl)propoxy, 4-(2-pentyloxyphenyl)butoxy, 5-(3-hexyloxyphenyl)pentyloxy, 6-(4-trifluoromethoxyphenyl)hexyloxy, 1,1-dimethyl-2-(2,4-dimethoxyphenyl)ethoxy, and 2-methyl-3-[2,4,6-tri(trifluoromethoxy)phenyl]propoxy groups.
Examples of the 1,2,3,4-tetrahydronaphthyl substituted lower alkyl group which may have 1 to 5 lower alkyl groups as substituents on the 1,2,3,4-tetrahydronaphthalene ring include 1,2,3,4-tetrahydronaphthyl substituted alkyl groups which may have 1 to 5 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the 1,2,3,4-tetrahydronaphthalene ring, and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1, 2, 5 or 6-)1,2,3,4-tetrahydronaphthylmethyl, 2-[(1, 2, 5 or 6-)1,2,3,4-tetrahydronaphthyl]ethyl, 1-[(1, 2, 5 or 6-)1,2,3,4-tetrahydronaphthyl]ethyl, 3-[(1, 2, 5 or 6-)1,2,3,4-tetrahydronaphthyl]propyl, 4-[(1, 2, 5 or 6-)1,2,3,4-tetrahydronaphthyl]butyl, 5-[(1, 2, 5 or 6-)1,2,3,4-tetrahydronaphthyl]pentyl, 6-[(1, 2, 5 or 6-)1,2,3,4-tetrahydronaphthyl]hexyl, 1,1-dimethyl-2-[(1, 2, 5 or 6-)1,2,3,4-tetrahydronaphthyl]ethyl, 2-methyl-3-[(1, 2, 5 or 6-)1,2,3,4-tetrahydronaphthyl]propyl, 1,1,4,4-tetramethyl(2, 3, 5 or 6-)1,2,3,4-tetrahydronaphthylmethyl, 1,1,4,4,5-pentamethyl(2, 3, 6, 7 or 8-)1,2,3,4-tetrahydronaphthylmethyl, 1,4,4-trimethyl(2, 3, 5, 6, 7 or 8-)1,2,3,4-tetrahydronaphthylmethyl, 5,6-dimethyl(2, 3, 7 or 8-)1,2,3,4-tetrahydronaphthylmethyl, 2-[1-methyl-(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydronaphthyl]ethyl, 1-[2-ethyl-(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydronaphthyl]ethyl, 3-[3-propyl-(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydronaphthyl]propyl, 4-[(4-butyl-(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydronaphthyl]butyl, 5-[5-pentyl-(1, 2, 3, 4, 6, 7 or 8-)1,2,3,4-tetrahydronaphthyl]pentyl, 6-[6-hexyl-(1, 2, 3, 4, 5, 7 or 8-)1,2,3,4-tetrahydronaphthyl]hexyl, 1,1-dimethyl-2-[1,7-dimethyl-(1, 2, 3, 4, 5, 6 or 8-)1,2,3,4-tetrahydronaphthyl]ethyl, and 2-methyl-3-[1,1,4-trimethyl-(2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydronaphthyl]propyl groups.
Examples of the piperidinyl group which may have 1 to 3 lower alkyl groups as substituents on the piperidine ring include piperidinyl group which may have 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the piperidine ring such as (1, 2, 3 or 4-)piperidinyl, 1-methyl-(2, 3 or 4-)piperidinyl, 1-ethyl-(2, 3 or 4-)piperidinyl, 1-propyl-(2, 3 or 4-)piperidinyl, 1-isopropyl-(2, 3 or 4-)piperidinyl, 1-butyl-(2, 3 or 4-)piperidinyl, 1-isobutyl-(2, 3 or 4-)piperidinyl, 1-tert-butyl-(2, 3 or 4-)piperidinyl, 1-pentyl-(2, 3 or 4-)piperidinyl, 1-hexyl-(2, 3 or 4-)piperidinyl, 1,2-dimethyl-(3, 4, 5 or 6-)piperidinyl, and 1,2,6-trimethyl-(3, 4 or 5-)piperidinyl groups.
Examples of the quinolyl lower alkyl group include quinolylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2, 3, 4, 5, 6, 7 or 8-)quinolylmethyl, 2-[(2, 3, 4, 5, 6, 7 or 8-)quinolyl]ethyl, 1-[(2, 3, 4, 5, 6, 7 or 8-)quinolyl] ethyl, 3-[(2, 3, 4, 5, 6, 7 or 8-)quinolyl]propyl, 4-[(2, 3, 4, 5, 6, 7 or 8-) quinolyl]butyl, 5-[(2, 3, 4, 5, 6, 7 or 8-) quinolyl]pentyl, and 6-[(2, 3, 4, 5, 6, 7 or 8-) quinolyl]hexyl groups.
Examples of the 1,2,3,4-tetrazolyl lower alkyl group which may have, on the tetrazole ring, a substituent selected from the group consisting of a lower alkyl group and a phenyl lower alkyl group include 1,2,3,4-tetrazolylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms and which may have, on the tetrazole ring, a substituent selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms and a phenyl alkyl group whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms, such as [(1 or 5-)1,2,3,4-tetrazolyl]methyl, 2-[(1 or 5-)1,2,3,4-tetrazolyl]ethyl, 1-[(1 or 5-)1,2,3,4-tetrazolyl]ethyl, 3-[(1 or 5-)1,2,3,4-tetrazolyl]propyl, 4-[(1 or 5-)1,2,3,4-tetrazolyl]butyl, 5-[(1 or 5-)1,2,3,4-tetrazolyl]pentyl, 6-[(1 or 5-)1,2,3,4-tetrazolyl]hexyl, 5-[1-methyl-5-(1,2,3,4-tetrazolyl)]pentyl, 6-[1-methyl-5-(1,2,3,4-tetrazolyl)]hexyl, 5-methyl-1-(1,2,3,4-tetrazolyl)methyl, 2-[5-ethyl-1-(1,2,3,4-tetrazolyl]hexyl, 1,1-dimethyl-2-[(1 or 5-)1,2,3,4-tetrazoly)]ethyl, 2-methyl-3-[(1 or 5-)1,2,3,4-tetrazolyl]propyl, [1-methyl-5-(1,2,3,4-tetrazolyl)]methyl, [1-ethyl-5-(1,2,3,4-tetrazolyl)]methyl, 2-[1-propyl-5-(1,2,3,4-tetrazolyl)]ethyl, 1-[1-butyl-5-(1,2,3,4-tetrazolyl)]ethyl, 3-[1-pentyl-5-(1,2,3,4-tetrazolyl)]propyl, 3-[5-propyl-1-(1,2,3,4-tetrazolyl)]propyl, 4-[5-butyl-1-(1,2,3,4-tetrazolyl)]butyl, 5-[5-pentyl-1-(1,2,3,4-tetrazolyl)]pentyl, 6-[5-hexyl-1-(1,2,3,4-tetrazolyl)]hexyl, [1-ethyl-5-(1,2,3,4-tetrazolyl)]methyl, [1-benzyl-5-(1,2,3,4-tetrazolyl)]methyl, 1-[(2-phenylethyl)-5-(1,2,3,4-tetrazolyl)]methyl, 2-[1-(3-phenylpropyl)-5-(1,2,3,4-tetrazolyl)]ethyl, 1-[1-(4-phenylbutyl)-5-(1,2,3,4-tetrazolyl)]ethyl, 3-[1-(5-phenylpentyl)-5-(1,2,3,4-tetrazolyl)]propyl, 4-[1-(6-phenylhexyl)-5-(1,2,3,4-tetrazolyl)]butyl, 5-[1-(1,1-dimethyl-2-phenylethyl)-5-(1,2,3,4-tetrazolyl)]methyl, 6-[1-(2-methyl-3-phenylpropyl)-5-(1,2,3,4-tetrazolyl)]hexyl, 5-benzyl-1-(1,2,3,4-tetrazolyl)methyl, 2-[5-(1-phenylethyl)-1-(1,2,3,4-tetrazolyl)]ethyl, 3-[5-(3-phenylpropyl)-1-(1,2,3,4-tetrazolyl)]propyl, 4-[5-(4-phenylbutyl)-1-(1,2,3,4-tetrazolyl)]butyl, 5-[5-(5-phenylpentyl)-1-(1,2,3,4-tetrazolyl)]pentyl, and 6-[5-(6-phenylhexyl)-1-(1,2,3,4-tetrazolyl)]hexyl groups.
Examples of the thiazolyl lower alkyl group which may have a phenyl group as a substituent on the thiazole ring include thiazolylalkyl groups which may have 1 or 2 phenyl groups as substituents on the thiazole ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(2, 4 or 5-)thiazolyl]methyl, 2-[(2, 4 or 5-)thiazolyl]ethyl, 1-[(2, 4 or 5-)thiazolyl]ethyl, 3-[(2, 4 or 5-)thiazolyl]propyl, 4-[(2, 4 or 5-)thiazolyl]butyl, 5-[(2, 4 or 5-)thiazolyl]pentyl, 6-[(2, 4 or 5-)thiazolyl]hexyl, 1,1-dimethyl-2-[(2, 4 or 5-)thiazolyl]ethyl, 2-methyl-3-[(2, 4 or 5-)thiazolyl]propyl, [2-phenyl-(4 or 5-)thiazolyl]methyl, 2-[4-phenyl-(2 or 5-)thiazolyl]ethyl, 1-[5-phenyl-(2 or 4-)thiazolyl]ethyl, 3-[2-phenyl-(2 or 5-)thiazolyl]propyl, 4-(2,4-diphenyl-5-thiazolyl)butyl, 5-(2,5-diphenyl-4-thiazolyl)pentyl, 6-(4,5-diphenyl-2-thiazolyl)hexyl, 1,1-dimethyl-2-[2-phenyl-(4 or 5-)thiazolyl]ethyl, 2-methyl-3-[4-phenyl-(2 or 5-)thiazolyl]propyl, [4-phenyl-(2 or 5-)thiazolyl]methyl, [5-phenyl-(2 or 4-)thiazolyl]methyl, (2,4-diphenyl-5-thiazolyl)methyl, (2,5-diphenyl-4-thiazolyl)methyl, and (4,5-diphenyl-2-thiazolyl)methyl groups.
Examples of the benzoyl lower alkyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkoxy group and a halogen atom include benzoylalkyl groups which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a linear or branched alkoxy group having 1 to 6 carbon atoms and a halogen atom and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as benzoylmethyl, 2-benzoylethyl, 1-benzoylethyl, 3-benzoylpropyl, 4-benzoylbutyl, 5-benzoylpentyl, 6-benzoylhexyl, 1,1-dimethyl-2-benzoylethyl, 2-methyl-3-benzoylpropyl, 4-fluorobenzoylmethyl, 2-chlorobenzoylmethyl, 3-chlorobenzoylmethyl, 4-chlorobenzoylmethyl, 2-(4-fluorobenzoyl)ethyl, 2-(4-chlorobenzoyl)ethyl, 3,4-dibromobenzoylmethyl, 3,4-diiodobenzoylmethyl, 2,4-difluorobenzoylmethyl, 2,5-dichlorobenzoylmethyl, 2,6-dichlorobenzoylmethyl, 3,4,5-trifluorobenzoylmethyl, 3-(4-chlorobenzoyl)propyl, 1-(2-bromobenzoyl)ethyl, 4-(3-fluorobenzoyl)butyl, 5-(4-iodobenzoyl)pentyl, 6-(4-chlorobenzoyl)hexyl, 1,1-dimethyl-2-(3-fluorobenzoyl)ethyl, 2-methyl-3-(4-chlorobenzoyl)propyl, 2-methoxybenzoylmethyl, 2-(3-methoxybenzoyl)ethyl, 2-(4-methoxybenzoyl)ethyl, 4-methoxybenzoylmethyl, 1-(2-ethoxybenzoyl)ethyl, 3-(3-ethoxybenzoyl)propyl, 4-(4-ethoxybenzoyl)butyl, 5-(4-isopropoxybenzoyl)pentyl, 6-(3-butoxybenzoyl)hexyl, 1,1-dimethyl-2-(4-pentyloxybenzoyl)ethyl, 2-methyl-3-(4-hexyloxybenzoyl)propyl, 3,4-dimethoxybenzoylmethyl, 3,4-diethoxybenzoylmethyl, 2,4-dimethoxybenzoylmethyl, 2,5-dimethoxybenzoylmethyl, 2,6-dimethoxybenzoylmethyl, 3,4,5-trimethoxybenzoylmethyl, 2-chloro-4-methoxybenzoylmethyl, and 3-fluoro-5-ethoxybenzoylmethyl groups.
Examples of the piperidinyl lower alkyl group which may have a lower alkyl group as a substituent on the piperidine ring include piperidinylalkyl groups which may have 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the piperidine ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(1, 2, 3 or 4-)piperidinyl]methyl, 2-[(1, 2, 3 or 4-)piperidinyl]ethyl, 1-[(1, 2, 3 or 4-)piperidinyl]ethyl, 3-[(1, 2, 3 or 4-)piperidinyl]propyl, 4-[(1, 2, 3 or 4-)piperidinyl]butyl, 5-[(1, 2, 3 or 4-)piperidinyl]pentyl, 6-[(1, 2, 3 or 4-)piperidinyl]hexyl, 1,1-dimethyl-2-[(1, 2, 3 or 4-)piperidinyl]ethyl, 2-methyl-3-[(1, 2, 3 or 4-)piperidinyl]propyl, [1-methyl-(2, 3 or 4-)piperidinyl]methyl, 2-[1-ethyl-(2, 3 or 4-)piperidinyl]ethyl, 1-[4-propyl-(1, 2 or 3-)piperidinyl]ethyl, 3-[3-isopropyl-(1, 2, 4, 5 or 6-)piperidinyl]propyl, 4-[2-butyl-(1, 3, 4, 5 or 6-)piperidinyl]butyl, 5-[1-isobutyl-(2, 3 or 4-)piperidinyl]pentyl, 6-[1-tert-butyl-(2, 3 or 4-)piperidinyl]hexyl, 1,1-dimethyl-2-[4-pentyl-(1, 2 or 3-)piperidinyl]ethyl, 2-methyl-3-[1-hexyl-(2, 3 or 4-)piperidinyl]propyl, [1,2-dimethyl-(3, 4, 5 or 6-)piperidinyl]methyl, and [1,2,6-trimethyl-(3, 4 or 5-)piperidinyl]methyl groups.
Examples of the imidazolyl group which may have 1 to 3 phenyl groups as substituents on the imidazole ring include imidazolyl groups which may have 1 to 3 phenyl groups as substituents on the imidazole ring such as (1, 2, 4 or 5-)imidazolyl, 1-phenyl-(2, 4 or 5-)imidazolyl, 2-phenyl-(1, 4 or 5-)imidazolyl, 4-phenyl-(1, 2 or 5-)imidazolyl, 5-phenyl-(1, 2 or 4-)imidazolyl, 1,2-diphenyl-(4 or 5-)imidazolyl, 2,4-diphenyl-(1 or 5-)imidazolyl, 4,5-diphenyl-(1 or 2-)imidazolyl, 2,5-diphenyl-(1 or 4-)imidazolyl, and 2,4,5-triphenyl-1-imidazolyl groups.
Examples of the benzimidazolyl group which may have 1 to 3 lower alkyl groups as substituents on the benzimidazole ring include benzimidazolyl group which may have 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents on the benzimidazole ring such as (1, 2, 4, 5, 6 or 7-)benzimidazolyl, 1-methyl-(2, 4, 5, 6 or 7-)benzimidazolyl, 2-ethyl-(1, 4, 5, 6 or 7-)benzimidazolyl, 4-propyl-(1, 2, 5, 6 or 7-)benzimidazolyl, 5-butyl-(1, 2, 4, 6 or 7-)benzimidazolyl, 6-pentyl-(1, 2, 4, 5 or 7-)benzimidazolyl, 7-hexyl-(1, 2, 4, 5 or 6-)benzimidazolyl, 1-ethyl-(2, 4, 5, 6 or 7-)benzimidazolyl]hexyl, 1-butyl-(2, 4, 5, 6 or 7-)benzimidazolyl, 1-isopropyl-(1, 2, 4, 5, 6 or 7-)benzimidazolyl, 1,2-dimethyl-(4, 5, 6 or 7-)benzimidazolyl, 1-methyl-4-ethyl-(2, 5, 6 or 7-)benzimidazolyl, 1-propyl-5-methyl-(2, 4, 6 or 7-)benzimidazolyl, and 1,2,5-trimethyl-(2, 4, 5, 6 or 7-)benzimidazolyl groups.
Examples of the pyridyl lower alkoxy group include pyridylalkoxy groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2, 3 or 4-)pyridylmethoxy, 2-[(2, 3 or 4-)pyridyl]ethoxy, 1-[(2, 3 or 4-)pyridyl]ethoxy, 3-[(2, 3 or 4-)pyridyl]propoxy, 4-[(2, 3 or 4-)pyridyl]butoxy, 1-1-dimethyl-2-[(2, 3 or 4-)pyridyl]ethoxy, 5-[(2, 3 or 4-)pyridyl]pentyloxy, 6-[(2, 3 or 4-)pyridyl]hexyloxy, 1-[(2, 3 or 4-)pyridyl]isopropoxy, and 2-methyl-3-[(2, 3 or 4-)pyridyl]propoxy groups.
Examples of the 1,2,3,4-tetrahydroquinolyl lower alkyl group which may have an oxo group as a substituent on the tetrahydroquinoline ring include 1,2,3,4-tetrahydroquinolylalkyl groups which may have 1 or 2 oxo groups as substituents on the tetrahydroquinoline ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolylmethyl, 2-[(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]ethyl, 1-[(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]ethyl, 3-[(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]propyl, 4-[(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]butyl, 5-[(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]pentyl, 6-[(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]hexyl, 1,1-dimethyl-2-[(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]ethyl, 2-methyl-3-[(1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]propyl, [2-oxo-(1, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]methyl, [4-oxo-(1, 2, 3, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]methyl, [2,4-dioxo-(1, 3, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]methyl, 2-[2-oxo-(1, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]ethyl, 3-[4-oxo-(1, 2, 3, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]propyl, 4-[2,4-dioxo-(1, 3, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]butyl, 5-[2-oxo-(1, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]pentyl, and 6-[4-oxo-(1, 2, 3, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]hexyl groups.
Examples of the 1,3,4-oxadiazolyl lower alkyl group which may have an oxo group as a substituent on the 1,3,4-oxadiazole ring include 1,3,4-oxadiazolylalkyl groups which may have an oxo group as a substituent on the 1,3,4-oxadiazole ring and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2 or 5-)1,3,4-oxadiazolylmethyl, 2-[(2 or 5-)1,3,4-oxadiazolyl]ethyl, 1-[(2 or 5-)1,3,4-oxadiazolyl]ethyl, 3-[(2 or 5-)1,3,4-oxadiazolyl]propyl, 4-[(2 or 5-)1,3,4-oxadiazolyl]butyl, 5-[(2 or 5-)1,3,4-oxadiazolyl]pentyl, 6-[(2 or 5-)1,3,4-oxadiazolyl]hexyl, 1,1-dimethyl-2-[(2 or 5-)1,3,4-oxadiazolyl]ethyl, 2-methyl-3-[(2 or 5-)1,3,4-oxadiazolyl]propyl, 2-oxo-[(3 or 5-)1,3,4-oxadiazolyl]methyl, 5-oxo-[(2 or 3-)1,3,4-oxadiazolyl]methyl, 2-[2-oxo-(3 or 5-)(1,3,4-oxadiazolyl)]ethyl, 1-[5-oxo-(2 or 3-)1,3,4-oxadiazolyl]ethyl, 3-[(2 or 5-)1,3,4-oxadiazolyl]propyl, 4-[2-oxo(3 or 5-)1,3,4-oxadiazolyl]butyl, 5-[5-oxo(2 or 3-)1,3,4-oxadiazolyl]pentyl, 6-[2-oxo(3 or 5-)1,3,4-oxadiazolyl]hexyl, 1,1-dimethyl-2-[5-oxo(2 or 3-)1,3,4-oxadiazolyl]ethyl, and 2-methyl-3-[2-oxo(3 or 5-)1,3,4-oxadiazolyl]propyl groups.
Examples of the thienyl lower alkyl group include thienylalkyl groups whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as (2 or 3-)thienylmethyl, 2-[(2 or 3-)thienyl]ethyl, 1-[(2 or 3-)thienyl]ethyl, 3-[(2 or 3-)thienyl]propyl, 4-[(2 or 3-)thienyl]butyl, 5-[(2 or 3-)thienyl]pentyl, 6-[(2 or 3-)thienyl]hexyl, 1,1-dimethyl-2-[(2 or 3-)thienyl]ethyl, and 2-methyl-3-[(2 or 3-)thienyl]propyl groups.
Examples of the pyrimidinylcarbonyl group which may have an oxo group as a substituent on the pyrimidine ring include pyrimidinylcarbonyl groups which may have 1 to 3 oxo groups as substituents on the pyrimidine ring such as (2, 3, 4 or 6-)pyrimidinylcarbonyl, 2,6-dioxo-(1, 3, 4 or 5-)pyrimidinylcarbonyl, 2-oxo-(1, 3, 4, 5 or 6-)pyrimidinylcarbonyl, 6-oxo-(1, 2, 3, 4 or 5-)pyrimidinylcarbonyl, 4-oxo-(1, 2, 3, 5 or 6-)pyrimidinylcarbonyl, 2,4-dioxo-(1, 3, 4 or 6-)pyrimidinylcarbonyl, and 2,4,6-trioxo-(1, 3 or 5-)pyrimidinylcarbonyl groups.
Examples of the lower alkoxy lower alkoxy group include linear or branched alkoxy groups having 1 to 6 carbon atoms which may have a linear or branched alkoxy group having 1 to 6 carbon atoms as a substituent such as methoxymethoxy, 1-ethoxyethoxy, 2-methoxyethoxy, 2-propoxyethoxy, 3-isopropoxypropoxy, 4-butoxybutoxy, 5-pentyloxypentyloxy, 6-hexyloxyhexyloxy, 1,1-dimethyl-2-methoxyethoxy, 2-methyl-3-ethoxypropoxy, and 3-methoxypropoxy groups.
Examples of the lower alkoxycarbonyl lower alkoxy group include alkoxycarbonylalkoxy groups whose two alkoxy moieties are linear or branched alkoxy groups having 1 to 6 carbon atoms such as methoxycarbonylmethoxy, ethoxycarbonylmethoxy, 2-methoxycarbonylethoxy, 2-ethoxycarbonylethoxy, 1-ethoxycarbonylethoxy, 3-methoxycarbonylpropoxy, 3-ethoxycarbonylpropoxy, 4-ethoxycarbonylbutoxy, 5-isopropoxycarbonylpentyloxy, 6-propoxycarbonylhexyloxy, 1,1-dimethyl-2-butoxycarbonylethoxy, 2-methyl-3-tert-butoxycarbonylpropoxy, 2-pentyloxycarbonylethoxy, and hexyloxycarbonylmethoxy groups.
Examples of the carboxy lower alkoxy group include carboxyalkoxy groups whose alkoxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms such as carboxymethoxy, 2-carboxyethoxy, 1-carboxyethoxy, 3-carboxypropoxy, 4-carboxybutoxy, 5-carboxypentyloxy, 6-carboxyhexyloxy, 1,1-dimethyl-2-carboxyethoxy, and 2-methyl-3-carboxypropoxy groups.
Examples of the phenoxy lower alkanoyl group include phenoxyalkanoyl groups whose alkanoyl moiety is a linear or branched alkanoyl group having 2 to 6 carbon atoms such as 2-phenoxyacetyl, 3-phenoxypropionyl, 2-phenoxypropionyl, 4-phenoxybutyryl, 5-phenoxypentanoyl, 6-phenoxyhexanoyl, 2,2-dimethyl-2-phenoxypropionyl, and 2-methyl-3-phenoxypropionyl groups.
Examples of the 1,2,3,4-tetrahydroquinolylcarbonyl group which may have an oxo group as a substituent on the tetrahydroquinoline ring include 1,2,3,4-tetrahydroquinolylcarbonyl groups which may have 1 or 2 oxo groups as substituents on the tetrahydroquinoline ring such as [(1, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]carbonyl, [2-oxo-(1, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]carbonyl, [4-oxo-(1, 2, 3, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]carbonyl, and [2,4-dioxo-(1, 3, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl]carbonyl groups.
Examples of the 1,2,3,4-tetrahydroquinolyl group which may have an oxo group as a substituent on the tetrahydroquinoline ring include 1,2,3,4-tetrahydroquinolyl groups which may have 1 or 2 oxo groups as substituents on the tetrahydroquinoline ring such as (1, 2, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl, 2-oxo-(1, 3, 4, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl, 4-oxo-(1, 2, 3, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl, and 2,4-dioxo-(1, 3, 5, 6, 7 or 8-)1,2,3,4-tetrahydroquinolyl groups.
Examples of the amino group which may have a lower alkoxycarbonyl group as a substituent include amino groups which may have an alkoxycarbonyl group whose akloxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms such as amino, methoxycarbonylamino, ethoxycarbonylamino, propoxycarbonylamino, isopropoxycarbonylamino, butoxycarbonylamino, tert-butoxycarbonylamino, pentyloxycarbonylamino, and hexyloxycarbonylamino groups.
Examples of the benzoyl group which may have 1 to 3 lower alkoxy groups as substituents on the phenyl ring include benzoyl groups which may have 1 to 3 linear or branched alkoxy groups having 1 to 6 carbon atoms as substituents on the phenyl ring such as benzoyl, 2-methoxybenzoyl, 3-methoxybenzoyl, 4-methoxybenzoyl, 2-ethoxybenzoyl, 3-ethoxybenzoyl, 4-ethoxybenzoyl, 4-isopropoxybenzoyl, 3-butoxybenzoyl, 4-pentyloxybenzoyl, 4-hexyloxybenzoyl, 3,4-dimethoxybenzoyl, 3,4-diethoxybenzoyl, 2,4-dimethoxybenzoyl, 2,5-dimethoxybenzoyl, 2,6-dimethoxybenzoyl, and 3,4,5-trimethoxybenzoyl groups.
Examples of the lower alkyl group which have 1 or 2 phenyls which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkoxycarbonyl group, a cyano group, a nitro group, a phenyl group, a halogen atom, a lower alkyl group which may have a halogen atom as a substituent, a lower alkoxy group which may have a halogen atom as a substituent, and a lower alkylthio group include, in addition to the above described phenyl lower alkyl groups, linear or branched alkyl groups which have 1 to 6 carbon atoms and 1 to 2 phenyls which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of an alkoxycarbonyl group whose akloxy moiety is a linear or branched alkoxy group having 1 to 6 carbon atoms, a cyano group, a nitro group, a phenyl group, a halogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, a linear or branched alkoxy group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents, and a linear or branched alkylthio group having 1 to 6 carbon atoms such as 1,1-diphenylmethyl, 1,1-di(4-fluorophenyl)methyl, 1-phenyl-1-(4-methoxyphenyl)methyl, 3,3-diphenylpropyl, 2,5-difluorobenzyl, 2,4-difluorobenzyl, 3,4-difluorobenzyl, 3,5-difluorobenzyl, 2,6-difluorobenzyl, 3-trifluoromethylbenzyl, 2-trifluoromethylbenzyl, 4-trifluoromethylbenzyl, 3,4-dimethoxybenzyl, 3,5-dimethoxybenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 2-methylbenzyl, 3-methylbenzyl, 4-methylbenzyl, 3,4-dimethylbenzyl, 2,3-dimethylbenzyl, 2-methoxybenzyl, 3-methoxybenzyl, 4-cyanobenzyl, 2-cyanobenzyl, 3-cyanobenzyl, 4-methoxybenzyl, 2,3-dichlorobenzyl, 2,4-dichlorobenzyl, 2,5-dichlorobenzyl, 3,4-dichlorobenzyl, 2,6-dichlorobenzyl, 4-fluorobenzyl, 3-fluorobenzyl, 2-fluorobenzyl, 4-nitrobenzyl, 3-nitrobenzyl, 2-nitrobenzyl, 3-trifluoromethoxybenzyl, 4-trifluoromethoxybenzyl, 2-trifluoromethoxybenzyl, 4-methoxycarbonylbenzyl, 3-methoxycarbonylbenzyl, 4-tert-butylbenzyl, 4-ethylbenzyl, 4-isopropylbenzyl, 4-methoxy-3-chlorobenzyl, 2-(4-methoxyphenyl)ethyl, 2-(4-fluorophenyl)ethyl, 2-(4-chlorophenyl)ethyl, 2-(3-methoxyphenyl)ethyl, 2-(4-methylphenyl)ethyl, 4-phenylbenzyl, 3,3-diphenylpropyl, 3-methyl-4-nitrobenzyl, 4-(4-methoxyphenyl)butyl, 2-(4-methylphenyl)ethyl, 4-tert-butoxycarbonylbenzyl, 3-chloro-6-methoxybenzyl, 4-nitro-3-methylbenzyl, 4-tert-butyrylbenzyl, 2-(2-ethoxycarbonylphenyl)ethyl, 1-(3-propoxycarbonylphenyl)ethyl, 3-(4-pentyloxycarbonylphenyl)propyl, 4-(3-hexyloxycarbonylphenyl)butyl, 5-(3,4-dimethoxycarbonylphenyl)pentyl, 6-(3,4,5-diethoxycarbonylphenyl)hexyl, 1,1-dimethyl-2-(4-butoxycarbonylphenyl)ethyl, 2-methyl-3-(4-methoxycarbonylphenyl)propyl, 2-(2-cyanophenyl)ethyl, 1-(3-cyanophenyl)ethyl, 3-(4-cyanophenyl)propyl, 4-(2-cyanophenyl)butyl, 5-(3-cyanophenyl)pentyl, 6-(4-cyanophenyl)hexyl, 1,1-dimethyl-2-(2,4-dicyanophenyl)ethyl, 2-methyl-3-(2,4,6-tricyanophenyl)propyl, 2-(2-nitrophenyl)ethyl, 1-(3-nitrophenyl)ethyl, 3-(4-nitrophenyl)propyl, 4-(2-nitrophenyl)butyl, 5-(3-nitrophenyl)pentyl, 6-(4-nitrophenyl)hexyl, 1,1-dimethyl-2-(2,4-dinitrophenyl)ethyl, 2-methyl-3-(2,4,6-trinitrophenyl)propyl, 2-(2-phenylphenyl)ethyl, 1-(3-phenylphenyl)ethyl, 3-(4-phenylphenyl)propyl, 4-(2-phenylphenyl)butyl, 5-(3-phenylphenyl)pentyl, 6-(4-phenylphenyl)hexyl, 1,1-dimethyl-2-(2,4-diphenylphenyl)ethyl, 2-methyl-3-(2,4,6-triphenylphenyl)propyl, 2-(2-fluorophenyl)ethyl, 1-(3-bromophenyl)ethyl, 3-(4-iodophenyl)propyl, 4-(2-bromophenyl)butyl, 5-(3-chlorophenyl)pentyl, 6-(4-bromophenyl)hexyl, 1,1-dimethyl-2-(2,4-dichlorophenyl)ethyl, 2-methyl-3-(2,4,6-trifluorophenyl)propyl, 2-(2-ethylphenyl)ethyl, 1-(3-propylphenyl)ethyl, 3-(4-butylphenyl)propyl, 4-(2-pentylphenyl)butyl, 5-(3-hexylphenyl)pentyl, 6-(4-trifluoromethylphenyl)hexyl, 1,1-dimethyl-2-(2,4-dimethylphenyl)ethyl, 2-methyl-3-[2,4,6-tri(trifluoromethyl)phenyl]propyl, 2-(2-ethoxyphenyl)ethyl, 1-(3-propoxyphenyl)ethyl, 3-(4-butoxyphenyl)propyl, 4-(2-pentyloxyphenyl)butyl, 5-(3-hexyloxyphenyl)pentyl, 6-(4-trifluoromethoxyphenyl)hexyl, 1,1-dimethyl-2-(2,4-dimethoxyphenyl)ethyl, 2-methyl-3-[2,4,6-tri(trifluoromethoxy)phenyl]propyl, 2-methylthiobenzyl, 3-methylthiobenzyl, 4-methylthiobenzyl, 3,4-dimethylthiobenzyl, 2,3-dimethylthiobenzyl, 2-(2-ethylthiophenyl)ethyl, 2-(4-methylthiophenyl)ethyl, 1-(3-propylthiophenyl)ethyl, 3-(4-butylthiophenyl)propyl, 4-(2-pentylthiophenyl)butyl, 5-(3-hexylthiophenyl)pentyl, 6-(4-methylthiophenyl)hexyl, 1,1-dimethyl-2-(2,4-dimethylthiophenyl)ethyl, 2-methyl-3-[2,4, 6-trimethylthiophenyl]propyl, 2-methyl-4-cyanobenzyl, 3-ethoxy-4-ethoxycarbonylbenzyl, 4-phenyl-3-nitrobenzyl, 3-fluoro-4-methoxybenzyl, 4-trifluoromethyl-3-cyanobenzyl, and 3-trifluoromethoxy-3-fluorobenzyl groups.
Examples of the phenyl group which may have, on the phenyl ring, 1 to 3 groups selected from the group consisting of a lower alkoxy group which may have a halogen atom as a substituent and a lower alkyl group which may have a halogen atom as a substituent include phenyl groups which may have, on the phenyl ring, 1 to 3 groups selected from the group consisting of a linear or branched alkoxy group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms as substituents and a linear or branched alkyl group having 1 to 6 carbon atoms and which may have 1 to 3 halogen atoms as substituents such as phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-butylphenyl, 4-pentylphenyl, 4-hexylphenyl, 3,4-dimethylphenyl, 3,4-diethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4,5-trimethylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 4-isopropoxyphenyl, 3-butoxyphenyl, 4-pentyloxyphenyl, 4-hexyloxyphenyl, 3,4-dimethoxyphenyl, 3,4-diethoxyphenyl, 2,4-dimethoxyphenyl, 2,5-dimethoxyphenyl, 2,6-dimethoxyphenyl, 3,4,5-trimethoxyphenyl, 2-trifluoromethoxyphenyl, 3-trifluoromethoxyphenyl, 4-trifluoromethoxyphenyl, 2-(bromomethoxy)phenyl, 3-(2-chloroethoxy)phenyl, 4-(2,3-dichloropropoxy)phenyl, 4-(4-fluorobutoxy)phenyl, 3-(5-chloropentyloxy)phenyl, 4-(5-bromohexyloxy)phenyl, 4-(5,6-dibromohexyloxy)phenyl, 3,4-di(trifluoromethoxy)phenyl, 3,4-di(4,4,4-trichlorobutoxy)phenyl, 2,4-di(3-chloro-2-methoxypropyl)phenyl, 2,5-di(3-chloropropoxy)phenyl, 2,6-di(2,2,2-trifluoroethoxy)phenyl, 3,4,5-tri(trifluoromethoxy)phenyl, 4-(2,2,2-trichloroethoxy)phenyl, 2-methyl-4-trifluoromethoxyphenyl, 3-ethyl-4-trichloromethoxyphenyl, 2-methoxy-4-trifluoromethoxyphenyl, 3-ethoxy-4-trichloromethoxyphenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2-(bromomethyl)phenyl, 3-(2-chloroethyl)phenyl, 4-(2,3-dichloropropyl)phenyl, 4-(4-fluorobutyl)phenyl, 3-(5-chloropentyl)phenyl, 4-(5-bromohexyl)phenyl, 4-(5,6-dibromohexyl)phenyl, 3,4-di(trifluoromethyl)phenyl, 3,4-di(4,4,4-trichlorobutyl)phenyl, 2,4-di(3-chloro-2-methylpropyl)phenyl, 2,5-di(3-chloropropyl)phenyl, 2,6-di(2,2,2-trifluoroethyl)phenyl, 3,4,5-tri(trifluoromethyl)phenyl, 4-(2,2,2-trichloroethyl)phenyl, 2-methyl-4-trifluoromethylphenyl, and 3-ethyl-4-trichloromethylphenyl groups.
Examples of the pyrrolidinyl lower alkyl group which may have, on the pyrrolidine ring, 1 to 3 lower alkyl groups which may have a hydroxyl group as a substituent include pyrrolidinylalkyl groups which may have, on the pyrrolidine ring, 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms which may have 1 to 3 hydroxyl groups as substituents and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(1, 2 or 3-)pyrrolidinyl]methyl, 2-[(1, 2 or 3-)pyrrolidinyl]ethyl, 1-[(1, 2 or 3-)pyrrolidinyl]ethyl, 3-[(1, 2 or 3-)pyrrolidinyl]propyl, 4-[(1, 2 or 3-)pyrrolidinyl]butyl, 5-[(1, 2 or 3-)pyrrolidinyl]pentyl, 6-[(1, 2 or 3-)pyrrolidinyl]hexyl, 1,1-dimethyl-2-[(1, 2 or 3-)pyrrolidinyl]ethyl, 2-methyl-3-[(1, 2 or 3-)pyrrolidinyl]propyl, [1-methyl-(2 or 3-)pyrrolidinyl]methyl, 2-[2-ethyl-(1, 3, 4 or 5-)pyrrolidinyl]ethyl, 1-[3-propyl-(1, 2, 4 or 5-)pyrrolidinyl]ethyl, 3-[1-butyl-(2 or 3-)pyrrolidinyl]propyl, 4-[2-pentyl-(1, 3, 4 or 5-)pyrrolidinyl]butyl, 5-[3-hexyl-(1, 2, 4 or 5-)pyrrolidinyl]pentyl, 6-[1,2-dimethyl-(3, 4 or 5-)pyrrolidinyl]hexyl, 1,1-dimethyl-2-[1,2,3-trimethyl-(4 or 5-)pyrrolidinyl]ethyl, 2-methyl-3-[1-ethyl-2-methyl-(3, 4 or 5-)pyrrolidinyl]propyl, [1-(2-hydroxyethyl)-(2 or 3-)pyrrolidinyl]methyl, [2-hydroxymethyl-(1, 3, 4 or 5-)pyrrolidinyl]methyl, 2-[2-hydroxymethyl-(1, 3, 4 or 5-)pyrrolidinyl]ethyl, 1-[3-(3-hydroxypropyl)-(1, 2, 4 or 5-)pyrrolidinyl]ethyl, 3-[1-(4-hydroxybutyl)-(2 or 3-)pyrrolidinyl]propyl, 4-[2-(5-hydroxypentyl)-(1, 3, 4 or 5-)pyrrolidinyl]butyl, 5-[3-(6-hydroxyhexyl)-(1, 2, 4 or 5-)pyrrolidinyl]pentyl, 6-[1,2-dihydroxymethyl-(3, 4 or 5-)pyrrolidinyl]hexyl, 1,1-dimethyl-2-[1,2,3-trihydroxymethyl-(4 or 5-)pyrrolidinyl]ethyl, 2-methyl-3-[2-(1,2-hydroxyethyl)-(1, 3, 4 or 5-)pyrrolidinyl]propyl, and [2-(2,3,4-trihydroxybutyl)-(1, 3, 4 or 5-)pyrrolidinyl]methyl groups.
Examples of the amino substituted lower alkyl group which may have a substituent selected from the group consisting of a phenyl group and a lower alkyl group include linear or branched alkyl groups having 1 to 6 carbon atoms substituted with an amino group which may have 1 or 2 substituents selected from the group consisting of a phenyl group and a linear or branched alkyl group having 1 to 6 carbon atoms such as aminomethyl, 2-aminomethyl, 1-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl, 1,1-dimethyl-2-aminoethyl, N,N-diethyl-2-aminoethyl, 2-methyl-3-aminopropyl, methylaminomethyl, 1-ethylaminoethyl, 2-propylaminoethyl, 3-isopropylaminopropyl, 4-butylaminobutyl, 5-pentylaminopentyl, 6-hexylaminohexyl, dimethylaminomethyl, 2-diisopropylaminoethyl, (N-ethyl-N-propylamino)methyl, 2-(N-methyl-N-hexylamino)ethyl, phenylaminomethyl, 1-phenylaminoethyl, 2-phenylaminoethyl, 3-phenylaminopropyl, 4-phenylaminobutyl, 5-phenylaminopentyl, 6-phenylaminohexyl, N-methyl-N-phenylaminomethyl, 2-(N-ethyl-N-phenylamino)ethyl, (N-ethyl-N-phenylamino)methyl, and 2-(N-methyl-N-phenylamino)ethyl groups.
Examples of the tetrahydrofuryl lower alkyl group which may have a hydroxyl group as a substituent on the lower alkyl group include tetrahydrofurylalkyl groups which may have a hydroxyl group as a substituent on the lower alkyl group and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as [(2 or 3-)tetrahydrofuryl]methyl, 2-[(2 or 3-)tetrahydrofuryl]ethyl, 1-[(2 or 3-)tetrahydrofuryl]ethyl, 3-[(2 or 3-)tetrahydrofuryl]propyl, 4-[(2 or 3-)tetrahydrofuryl]butyl, 5-[(2 or 3-)tetrahydrofuryl]pentyl, 6-[(2 or 3-)tetrahydrofuryl]hexyl, 1,1-dimethyl-2-[(2 or 3-)tetrahydrofuryl]ethyl, 2-methyl-3-[(2 or 3-)tetrahydrofuryl]propyl, 1-hydroxy-1-[(2 or 3-)tetrahydrofuryl]methyl, 2-hydroxy-2-[(2 or 3-)tetrahydrofuryl]ethyl, 2-hydroxy-1-[(2 or 3-)tetrahydrofuryl]ethyl, 3-hydroxy-3-[(2 or 3-)tetrahydrofuryl]propyl, 4-hydroxy-4-[(2 or 3-)tetrahydrofuryl]butyl, 5-hydroxy-5-[(2 or 3-)tetrahydrofuryl]pentyl, 6-hydroxy-6-[(2 or 3-)tetrahydrofuryl]hexyl, 2-hydroxy-1,1-dimethyl-2-[(2 or 3-)tetrahydrofuryl]ethyl, and 3-hydroxy-2-methyl-3-[(2 or 3-)tetrahydrofuryl]propyl groups.
Examples of the phenoxy lower alkyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a lower alkyl group and a nitro group include, in addition to the above described phenoxy lower alkyl groups, phenoxyalkyl groups which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a linear or branched alkyl group having 1 to 6 carbon atoms and a nitro group and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as 2-methylphenoxymethyl, 3-methylphenoxymethyl, 4-methylphenoxymethyl, 3,4-dimethylphenoxymethyl, 2,3-dimethylphenoxymethyl, 3,4,5-trimethylphenoxymethyl, 2-(2-ethylphenoxy)ethyl, 2-(3-methylphenoxy)ethyl, 2-(4-methylphenoxy)ethyl, 1-(3-propylphenoxy)ethyl, 3-(4-butylphenoxy)propyl, 4-(2-pentylphenoxy)butyl, 5-(3-hexylphenoxy)pentyl, 6-(4-methylphenoxy)hexyl, 1,1-dimethyl-2-(2,4-dimethylphenoxy)ethyl, 2-methyl-3-(2,4,6-trimethylphenoxy)propyl, 2-(4-nitro-3-methylphenoxy)ethyl, 4-nitrophenoxymethyl, 3-nitrophenoxymethyl, 2-nitrophenoxymethyl, 2-(2-nitrophenoxy)ethyl, 2-(4-nitrophenoxy)ethyl, 1-(3-nitrophenoxy)ethyl, 3-(4-nitrophenoxy)propyl, 4-(2-nitrophenoxy)butyl, 5-(3-nitrophenoxy)pentyl, 6-(4-nitrophenoxy)hexyl, 1,1-dimethyl-2-(2,4-dinitrophenoxy)ethyl, and 2-methyl-3-(2,4,6-trinitrophenoxy)propyl groups.
Examples of the phenyl lower alkanoyl group include phenylalkanoyl groups whose alkanoyl moiety is a linear or branched alkanoyl group having 2 to 6 carbon atoms such as 2-phenylacetyl, 3-phenylpropionyl, 2-phenylpropionyl, 4-phenylbutyryl, 5-phenylpentanoyl, 6-phenylhexanoyl, 2,2-dimethyl-3-phenylpropionyl, and 2-methyl-3-phenylpropionyl groups.
Examples of the phenyl group which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a halogen atom and a lower alkyl group which may have a halogen atom include phenyl groups which may have, on the phenyl ring, 1 to 3 substituents selected from the group consisting of a halogen atom and a linear or branched alkyl group having 1 to 6 carbon atoms which may have 1 to 3 halogen atoms such as phenyl, 3,4-difluorophenyl, 2-fluorophenyl, 3-bromophenyl, 4-iodophenyl, 4-methylphenyl, 2-methylphenyl, 3-methylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 4-isopropylphenyl, 3-butylphenyl, 4-pentylphenyl, 4-hexylphenyl, 3,4-dimethylphenyl, 3,4-diethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4,5-trimethylphenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2-(bromomethyl)phenyl, 3-(2-chloroethyl)phenyl, 4-(2,3-dichloropropyl)phenyl, 4-(4-fluorobutyl)phenyl, 3-(5-chloropentyl)phenyl, 4-(5-bromohexyl)phenyl, 4-(5,6-dibromohexyl)phenyl, 3,4-di(trifluoromethyl)phenyl, 3,4-di(4,4,4-trichlorobutyl)phenyl, 2,4-di(3-chloro-2-methylpropyl)phenyl, 2,5-di(3-chloropropyl)phenyl, 2,6-di(2,2,2-trifluoroethyl)phenyl, 3,4,5-tri(trifluoromethyl)phenyl, 4-(2,2,2-trichloroethyl)phenyl, 2-methyl-4-trifluoromethylphenyl, 3-ethyl-4-trichloromethylphenyl, 2-chloro-4-trifluoromethylphenyl, 3-ethyl-4-fluorophenyl, 3-fluoro-4-trichloromethylphenyl, 2-methyl-3-trifluoromethyl-4-trifluoromethylphenyl, 3-fluorophenyl, 4-fluorophenyl, 2-bromophenyl, 4-bromophenyl, 2-iodophenyl, 3-iodophenyl, 2,3-dibromophenyl, 2,4-diiodophenyl, 2,5-difluorophenyl, 2,6-dichlorophenyl, 2,4,6-trichlorophenyl, 2,4-difluorophenyl, 3,5-difluorophenyl, 2,6-difluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 2,5-dichlorophenyl, 3,4-dichlorophenyl, 2,6-dichlorophenyl, 3,5-dichlorophenyl, 2,4,6-trifluorophenyl, and 2,4-difluorophenyl groups.
Examples of the 5-to 7-membered saturated heterocyclic group formed by mutually binding R20 and R21, R22 and R23, R26 and R27, R29 and R30 or R32 and R33 together with the nitrogen atoms bound to them, through or not through a nitrogen atom, an oxygen atom or a sulfur atom, include pyrrolidinyl, piperidinyl, piperazinyl, morpholino, thiomorpholino, and homopiperazinyl groups.
Examples of the phenoxy lower alkyl group which may have, on the phenyl ring, a lower alkyl group as a substituent include, in addition to the above described phenoxy lower alkyl groups, phenoxyalkyl groups which may have, on the phenyl ring, 1 to 3 linear or branched alkyl groups having 1 to 6 carbon atoms as substituents and whose alkyl moiety is a linear or branched alkyl group having 1 to 6 carbon atoms such as 2-methylphenoxymethyl, 3-methylphenoxymethyl, 4-methylphenoxymethyl, 3,4-dimethylphenoxymethyl, 2,3-dimethylphenoxymethyl, 3,4,5-trimethylphenoxymethyl, 2-(2-ethylphenoxy)ethyl, 2-(4-methylphenoxy)ethyl, 1-(3-propylphenoxy)ethyl, 3-(4-butylphenoxy)propyl, 4-(2-pentylphenoxy)butyl, 5-(3-hexylphenoxy)pentyl, 6-(4-methylphenoxy)hexyl, 1,1-dimethyl-2-(2,4-dimethylphenoxy)ethyl, and 2-methyl-3-(2,4,6-trimethylphenoxy)propyl groups.
A compound represented by the general formula (1) or a salt thereof is more preferred, wherein
For example, a compound represented by the general formula (1) or a salt thereof is further more preferred, wherein
Another more preferred example is a compound represented by the general formula (1) or a salt thereof, wherein
The aromatic compound (1) or a salt thereof contained in the STAT3/5 activation inhibitor of the present invention includes a stereoisomer, optical isomer and solvate (hydrate, ethanolate, etc.).
Of the aromatic compounds (1), a compound having a basic group may be easily reacted with a conventional pharmacologically acceptable acid to form a salt. Examples of such acid include mineral acids such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, and phosphoric acid, and organic acids such as methanesulfonic acid, p-toluenesulfonic acid, acetic acid, citric acid, tartaric acid, maleic acid, fumaric acid, malonic acid, and lactic acid.
Of the aromatic compounds (1), a compound having an acidic group may be easily reacted with a conventional pharmacologically acceptable basic compound to form a salt. Examples of such a salt include a sodium salt, a potassium salt, and a calcium salt.
The aromatic compound (1) or a salt thereof can be prepared in the same manner as in WO2006/014012.
Next, a medical formulation containing the aromatic compound (1) or a salt thereof as an active ingredient will be described.
The medical formulation is obtained by formulating the aromatic compound (1) or a salt thereof in the form of pharmaceutical preparation, and more specifically, prepared using a diluent or an excipient such as a filler, expander, binder, moistener, disintegrator, surfactant, or lubricant.
The form of such a medicinal formulation may be chosen from various forms depending upon the therapeutic purpose, and typical forms include tablets, pills, powders, liquids, suspensions, emulsions, granules, capsules, suppositories, and injections (liquids, suspensions).
The carrier to be used in forming tablets may be chosen widely from conventionally known ones. Examples of the carrier include excipients such as lactose, saccharose, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, and crystalline cellulose, binders such as water, ethanol, propanol, simple syrup, a glucose solution, a starch solution, a gelatin solution, carboxymethylcellulose, shellac, methylcellulose, potassium phosphate, and polyvinylpyrrolidone, disintegrators such as dried starch, sodium arginate, agar powder, laminaran powder, sodium bicarbonate, calcium carbonate, polyoxyethylene sorbitan fatty acid ester, sodium lauryl sulfate, stearic acid monoglyceride, starch, and lactose, anti-disintegrators such as saccharose, stearine, cacao butter, and hydrogenated oil, absorbefacients such as quartenary ammonium base and sodium lauryl sulfate, wetting agents such as glycerol and starch, adsorbents such as starch, lactose, kaolin, bentonite, and colloidal silicate, and lubricants such as purified talc, stearate, boric acid powder, and polyethylene glycol.
Further, tablets may be coated in a conventional manner as needed. Examples of coated tablets include sugar-coated tablets, gelatin-coated tablets, enteric-coated tablets, film-coated tablets, or double or multi-layered tablets.
The carriers to be used in forming pills may be chosen widely from the conventionally known ones. Examples of the carrier include excipients such as glucose, lactose, starch, cacao butter, hydrogenated vegetable oil, kaolin, and talc, binders such as gum arabic powder, tragacanth powder, gelatin, and ethanol, and disintegrators such as laminaran and agar.
The carriers to be used in forming suppositories may be chosen widely from the conventionally known ones. Examples of the carrier include polyethylene glycol, cacao butter, higher alcohols, esters of higher alcohols, gelatin, and semi-synthetic glycerides.
When liquid, emulsion and suspension are prepared as injection preparations, they are preferably sterilized and controlled to be isotonic with the blood. Diluents to be used in forming these liquid, emulsion and suspension preparations may be chosen widely from the conventionally known ones. Examples of the diluents include water, ethanol, propylene glycol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, and polyoxyethylene sorbitan fatty acid ester. In this case, the medical formulations may contain sodium chloride, glucose or glycerol in a sufficient amount to prepare isotonic solutions. Also, conventional solubilizers, buffers, analgesics, and the like, and, as necessary, coloring agents, preservatives, spices, flavors, sweets and the like, or other pharmaceuticals may be contained.
Although the amount of the aromatic compound (1) or a salt thereof contained in a medical formulation is not particularly limited and may be appropriately selected from a wide range of compounds. It is preferable that the aromatic compound (1) or a salt thereof is contained in an amount of 1 to 70 wt % in a medical formulation.
The method for administrating a medical formulation according to the present invention is not particularly limited. The medical formulation can be administered by a method determined depending upon the form of medical formulation, patient's age, sex, severity of the disease and other conditions. For example, tablets, pills, liquids, suspensions, emulsions, granules and capsules are administered orally. The injection formulations are administered singly or by mixing with a conventional fluid replacement such as a glucose solution or amino acid solution, intravenously or, as necessary, singly administered intramuscularly, intradermally, subcutaneously or intraperitoneally. Suppositories are administered into the rectum.
The dosage for the above mentioned medical formulation may be chosen appropriately depending upon the usage, patient's age, sex and severity of the disease and other conditions. Typically, 0.001 to 100 mg per kg (body weight) per day, preferably 0.001 to 50 mg per kg (body weight) per day, is administered once or in several times a day.
Since the above described dosage varies depending upon various conditions, the dosage may be smaller than the lower limit of the range described above or larger than the upper limit of the range described above.
The aromatic compound (1) or a salt thereof in the present invention has a STAT3/5 activation inhibitory action and useful as a STAT3/5 activation inhibitor.
The aromatic compound (1) or a salt thereof has a STAT3 activation inhibitory action and therefore useful as a medicinal drug for preventing or treating autoimmune disease, diabetes, infection, central disease, cancer-associated disease or psoriasis.
Examples of the autoimmune disease include autoimmune blood dyscrasia (for example, hemolytic anemia, aplastic anemia and idiopathy thrombocytopenia), rheumatism, systemic lupus erythematosus, polychondritis, scleroderma, Wegener's granulomatosis, dermatomyositis, chronic active hepatitis, severe myasthenic, Stevens-Johnson syndrome, idiopathic sprue, inflammatory bowel disease (for example, ulcerative colitis and Crohn disease), endocrine ophthalmopathy, Graves' disease, sarcoidosis, multiple sclerosis, primary biliary cirrhosis, juvenile-onset diabetes (Type I diabetes), uveitis (front and rear uveitis), keratoconjunctivitis sicca, vernal keratoconjunctivitis, psoriatic arthritis, glomerulonephritis (with and without a nephrosis symptom, such as idiopathic nephrotic syndrome or minimal-change nephropathy).
As the central disease, Alzheimer's disease may be mentioned.
As the cancer-associated disease, cachexia may be mentioned.
As the infection, infection with hepatitis C virus (HCV) and infection with Kaposi's sarcoma-associated herpes virus (KSHV) may be mentioned.
Further, the compound of the present invention has a STAT5 activation inhibitory action and is useful as STAT5 activation inhibitor, specifically as preventive or treating agent for autoimmune diseases, allergies, inflammations, hyperprolactinemia and the like as mentioned above.
In the present invention, the aromatic compound (1) or a salt thereof may be used in combination with another STAT3 activation inhibitor, STAT3 activity inhibitor, immunosuppressive agent, antiphlogistic, therapeutic agent for diabetes, therapeutic agent for infectious disease, therapeutic agent for central disease, therapeutic agent for cancer-associated, therapeutic agent for psoriasis, antitumor agent, and fibrosis suppressive agent.
The patents, patent applications and literatures cited in the present invention are incorporated herein by reference.
Effect of test compound on the amount of STAT3 activated in nucleus of Hep G2 cells after stimulation with IL-6
1) Culture
After Hep G2 cells are washed with PBS (−) twice, they are washed once with trypsin/EDTA solution and detached using trypsin/EDTA solution. The cells are centrifuged and suspended in a medium supplemented with antibiotics (MEM medium (10% FBS +antibiotic (100 U/mL penicillin+100 μg/mL streptomycin)). After the number of cells is counted, the cells are seeded on 12-well plates at a density of 1.2×105 cells/1 mL per well.
Two days after seeding, the culture medium is replaced with 1 mL of antibiotic-free culture medium (MEM medium (10% FBS)).
2) Addition of Test Compound
Two days after medium replacement, a test compound is added so as to obtain concentrations of 0, 1, 10 and 100 nM.
Three hours after addition of the test compound, IL-6 (Code No. KTS102S manufactured by Kamakura Techno Science Inc.) is added at a final concentration 0 or 500 ng/mL.
Five minutes after addition of IL-6, extraction is performed by use of a Nuclear Extraction Kit (Code No. 40410 manufactured by Active Motif Inc.)
3) Extraction of Nuclear Fraction
The supernatant of the cells is removed by suction. The cells are washed with 1 mL of ice-cold phosphatase inhibitor-containing PBS (hereinafter, PBS/phosphatase inhibitor) and the supernatant of the cells is again removed by suction.
The cells are collected with a cell scraper in 0.6 mL of ice-cold PBS/phosphatase inhibitors and divided into ice-cold 1.5 mL microtubes.
After the microtube is centrifuged at 4° C. and a rate of 400×g for 5 minutes, the supernatant is removed.
The cells are resuspended in 0.2 mL of hypotonic buffer by pipetting up and down several times and kept on ice for 15 minutes.
To this suspension, 10 μL of a detergent is added and vortexed for 10 seconds. After centrifugation is performed at 4° C. and a rate of 20,400×g for 30 seconds, the supernatant is removed.
To the resultant cells, 50 μL of Complete Lysis Buffer is added. The suspension is pipetted, vortexed for 10 seconds and shaken on ice for 30 minutes.
After vortexed for 30 seconds, the suspension is centrifuged at 4° C. and a rate of 20,400×g for 10 minutes.
The supernatant is divided into ice-cold 1.5 mL microtubes and stored at −80° C.
4) DNA Binding is Measured by use of TransAM STAT3 Kit (Code No. 45196 Manufactured by Active Motif Inc.)
To each of the wells of an ELISA plate, 30 μL of Complete Binding Buffer and 20 μL of a sample (extracted from a nucleus) are added.
A positive control: 10 μl of Hep G2 nuclear extract (2.5 mg/mL) is diluted with 40 μL of Complete Lysis Buffer (10 μg/20 μL). Dilutions were prepared at 5, 2.5, 1.25, 0.625 and 0.313 μg/20 μL by sequential half-fold dilution, and 20 μL of dilutions is added to each well.
Blank well: 20 μL of Complete Lysis Buffer is added.
After the plate is sealed, the plate is gently shaken at room temperature for one hour, followed by washing with 200 μL of washing buffer three times.
100 μL of a STAT3 antibody is added and the plate is sealed. Thereafter, the plate is gently shaken at room temperature. One hour later, the plate is washed with 200 μL of washing buffer three times. After washing, 100 μL of an HRP-conjugated antibody is added. The plate is sealed, gently shaken at room temperature for one hour, followed by washing with 200 μL of washing buffer four times.
After that, 100 μL of developing solution returned to room temperature is added, and the plate is incubated for 2 to 10 minutes protected from light. After color development is confirmed, 100 μL of stop solution is added and absorbance at 450 nm and 630 nm is determined within 5 minutes.
5) The Results of Test Compounds Listed in Table 1 Below are Shown in Table 2.
Effect of Test Compound on Suppressing Phosphorylation of STAT3
(1) Cells
Seeding of Cells
After Hep G2 cells are washed with PBS (−) twice, they are washed and removed by trypsin/EDTA and further removed by trypsin/EDTA. The cells are centrifuged and suspended in a medium supplemented with antibiotics (MEM medium (10% FBS +antibiotic (100 U/mL penicillin+100 μg/mL streptomycin))). After the number of cells is counted, the cells are seeded in a 6-well plate in a rate of 2.4×105/2 mL per well.
Two days later, the medium supplemented with antibiotics is replaced with a medium supplemented with no antibiotics (MEM medium (10% FBS)).
Treatment of Cells with Medicinal Drug
Two days after medium replacement, a test compound is added so as to obtain concentrations of 0, 1, 10 and 100 nM.
Three hours after addition of the test compound, IL-6 (Code No. KTS102S manufactured by Kamakura Techno Science Inc.) is added so as to obtain a concentration 100 ng/mL.
Recovery of Cells
Five minutes after addition of IL-6, the cells are washed with cooled PBS (−) twice, and peeled off from the plate by a scraper. The cells are collected in a 1.5 mL microtube by use of PBS (−). The cells collected in the 1.5 mL microtube are centrifuged and the supernatant is removed. The cells collected in the 1.5 mL microtube are cryopreserved in a cryogenic refrigerator until use.
Lysis Treatment
To the frozen cells, RIPA buffer is added. The frozen cells are suspended by use of 1 mL syringe with a 26G×½ injection needle and the suspension solution is allowed to stand still in ice water for 30 to 60 minutes. The cell suspension solution is centrifuged and the supernatant (cell lysate) is transferred to a new tube. The cell lysate collected in the tube is cryopreserved in a cryogenic refrigerator until use.
Measurement of Protein Concentration
The amount of protein of each cell lysate is measured in accordance with the protocol attached to a BCA protein assay reagent set.
(2) Western Blotting Analysis
PAGE (Electrophoresis)
After the protein amount of each cell lysate is set at the same value, denature treatment is performed under reduced conditions. After the samples and a molecular marker are applied to polyacrylamide gel, electrophoresis is performed.
Blotting
After completion of electrophoresis, the gel is equilibrated with the solution to be used in transferring.
The proteins developed on the polyacrylamide gel are transferred onto a PVDF (polyvinylidene difluoride) film by a semidry type transferring apparatus.
Blocking/Washing
After the PVDF film is washed, it is soaked in blocking buffer (5% BSA) to perform blocking.
Primary Antibody (Phospho-STAT3 (Ser 727) Antibody or Phospho-STAT3 (Tyr 705) Antibody)
Blocked PVDF film is reacted with the primary antibody.
Secondary Antibody (Anti-Rabbit-IgG HRP-Linked Antibody)/Washing
After washed, the PVDF film is reacted with the HRP labeled antibody.
Detection of Color Emission by ECL
After the PVDF film is washed, color is allowed to emit by use of ECL Western Blotting Detection Reagents and fluorescence is detected by LAS-3000.
According to the Aforementioned Method, the Effect of the Test Compound on Surppressing Phosphorylation of STAT3 is Measured.
Effect of test compound on prolactin-induced STAT5 activation in 22Rv1 cells
1) Culture
After 22Rv1 cells cryopreserved are subcultured at least twice, they are subjected to a test. After culture until subconfluency, the cells are washed with D-PBS (−). Thereafter, they are detached using trypsin/EDTA solution and suspended in a medium (RPMI-1640 medium (10% FBS+antibiotics (100 U/mL penicillin+100 μg/mL streptomycin)). The cell suspension solution is centrifuged at 150×g, for 5 minutes at 20 to 25° C. The supernatant is removed and the pellet is resuspended in the medium. An aliquot of the cell suspension solution is taken and dead cells are stained with trypan blue. The number of viable cells is counted by a hemocytometer. A cell suspension solution is prepared so as to contain 2×105 cells/mL, and cells are seeded in a 12 well-plate in a rate of 2×105 cells/mL per well. Cells are cultured in a CO2 incubator (5% CO2, 37° C.)
2) Addition of Test Compound
Two days after seeding, a test compound is added so as to obtain concentrations of 0 and 1000 nM.
Three hours after addition of the test compound, recombinant human prolactin (rhPRL, R&D systems Inc.) is added so as to obtain a concentration of 0 or 250 ng/mL.
3) Extraction of Cytoplasmic Fraction
Fifteen minutes after addition of prolactin, extraction is performed by a Nuclear Extract Kit (Code No. 40410 manufactured by Active Motif Inc.). At 15 minutes after the addition of prolactin, the supernatant is removed and prolactin-stimlation is immediately stopped by adding 1 ml of ice-cold PBS/phosphatase inhibitor. After aspirating 1 mL of ice-cold PBS/phosphatase inhibitor, 0.6 mL of ice-cold PBS/phosphatase inhibitor is added and centrifuged at 200×g, for 5 minutes at 4° C.
After the supernatant is removed, 0.2 mL of hypotonic buffer is added and suspended. After the suspension is kept on ice for 15 minutes, 10 μL of a detergent is added. After the solution is further stirred, it is centrifuged at 14,000×g, for one minute at 4° C. The resultant supernatant (cytoplasmic fraction) is divided to three ice-cold 96-well plates, and stored in a freezer of −80° C.
4) Measurement of Activated STATS
Measurement is performed by use of reagents attached to TransAM™STAT family kit. To describe more specifically, to each of the wells of an ELISA plate of the TransAM™STAT family kit, 30 μL of Complete Binding Buffer is added, and thereafter, 20 μL of the cytoplasmic fraction is added. As a sample for calibration curve, 12 μL of a cell nuclear fraction reference sample (Nb2 nuclear fraction (prolactin stimulated, 2.5 μg/μL)) attached to the TransAM™STAT family kit is diluted with 48 μL of Complete Lysis Buffer (to 10 μg/20 μL), and further serially diluted in half to prepare diluted solutions of 5, 2.5, 1.25, 0.625, 0.313, and 0.156 μg/20 μL. 20 μl of each of the dilution solution is added to well. As a blank, 20 μL of Complete Lysis Buffer is added. After addition of a sample, the plate is sealed and gently shaken at room temperature for one hour. After that, the plate is washed with 200 μL of wash buffer three times. Next, 100 μL of STAT5B antibody is added, sealed and incubated at room temperature without agitation. One hour later, the plate is washed with 200 μL of wash buffer three times. 100 μL of a Horseradish Peroxidase (HRP)-conjugated antibody is added, sealed and incubated at room temperature without agitation. One hour later, the plate is washed with 200 μL of wash buffer four times and 100 μL of a developing solution is added. The plate is incubated for 2 to 10 minutes protected from light. After color development is confirmed, 100 μL of a stop solution is added. Immediately after, absorbance at 450 nm (measurement wavelength) and 630 nm (reference wavelength) is determined using a plate reader.
The amount of phosphorylated STAT5B dimer is estimated based on a calibration curve. Further, a ratio (T/C %) of the amount of phosphorylated STAT5B dimer in the presence of each medicinal drug relative to that in the absence of a medicinal drug is calculated. The results of test compounds listed in Table 1 are shown in Table 3.
Effect of test compound on dextran sulfate sodium (DSS) induced colitis model
1. Induction of Colitis by DSS
After female mice C57BL/6J Jms Slc are preliminarily raised for a week, the mice are grouped based on the body weight (BW) of the mice at the grouping day and in accordance with stratified random sampling.
DSS (Lot No, 4556J, MP Biomedicals) is dissolved in Otsuka distilled water to prepare a 4% DSS solution. Mice are allowed to drink the 4% DSS solution freely for 7 days from the following day (Day 2) after initiation of administration to induce colitis.
2. Administration of Test Compound and Solvent
Based on the body weight before administration of the DSS solution (Day 1) and the most recent body weight after administration of the DSS solution, each administration solution is orally administered in a dose of 10 mL/kg once a day.
The dose of the test compound is 300 mg/kg.
An administration solution is prepared by suspending a test compound in a 5% gum arabic solution so as to contain the test compound in a concentration of 30 mg/mL.
3. Autopsy
Autopsy is performed at Day 8.
4. Collection of Blood
After blood is collected from the abdominal posterior vena cava under anaesthesia with diethyl ether, it is immediately transferred to a BD Microtainer® (Nippon Becton, Dickinson and Company), mixed by overturning the Micro-Tina and allowed to stand still in ice. The Micro-Tina is centrifuged by use of a refrigerated centrifuge (HITACHI CF9RX, T3S51 rotor) at 4° C. and 2,150×g for 20 minutes to obtain heparin plasma. The plasma dispensed is cryopreserved in a freezer (−80° C.) until use in measurement.
5. Collection of Organ
After the abdominal posterior vena cava is cut under anaesthesia with diethyl ether to kill a mouse by blood letting, the spleen is excised out. The weight of the spleen is measured by an electronic force balance. And, the large intestine was immediately removed for measurement of intestinal length and evaluation of intestinal shortening.
6. Measurement Items
Body Weight
Body weight is measured at Day 1 (day of grouping), 3, 5, 7 and 8 (day of autopsy) by an electronic force balance.
Based on the body weight of Day 1 (day of grouping) and Day 8 (day of autopsy), a body weight change is calculated.
Spleen Weight
The wet weight of the spleen is measured by an electronic force balance.
In addition, from the measurement results of spleen weight, a ratio (T/C %) of the spleen weight relative to an average spleen weight of a control group and a spleen weight gain inhibition ratio (IR %) are calculated.
Intestinal Length
The length of the large intestine is measured by a scale.
In addition, from the measurement results of intestinal length, a ratio (T/C%) of the intestinal length relative to an average intestinal length of a control group and an intestinal shortening inhibition ratio (IR%) are calculated.
The results of test compounds are shown in Table 4.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2006-271172 | Oct 2006 | JP | national |
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|---|---|---|---|---|
| PCT/JP2007/069645 | 10/2/2007 | WO | 00 | 4/1/2009 |
| Publishing Document | Publishing Date | Country | Kind |
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| WO2008/044667 | 4/17/2008 | WO | A |
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