Patent EA-002357-B1 (EA)
Title: Benzimidazole derivatives
Inventor: YAMASAKI NORITSUGU
IPC: C07D403/12
Filed: 1996-12-27
Abstract: 1. A pharmaceutical composition for preventing and treating impaired glucose tolerance, diabetes, diabetic complications, syndrome of insulin resistance, hyperlipidemia, atherosclerosis, cardiovascular disorders, hyperglycemia or hypertension; or stenocardia, hypertension, pulmonary hypertension, congestive heart failure, glomerulopathy, tubulointerstitial disorders, renal failure, atherosclerosis, angiostenosis, distal angiopathy, cerebral apoplexy, chronic reversible obstructions, allergic rhinitis, urticaria, glaucoma, diseases characterized by enteromotility disorders, impotence, diabetic complications, nephritis, cancerous cachexia, or restenosis after PTCA, which comprises, as an active ingredient, a compound of the following formula:   wherein R6 represents an aryl-lower alkyl group or an aryl-lower alkyl group substituted by one or two substituents selected from a halogen atom, a haloaryl group, a lower alkyl group, a halo-lower alkyl group, a lower alkoxy group, a nitro group, an amino group, a cyano group, an aryl group, a cyanoaryl group, an aryl-lower alkyloxy group, an arylsulfonyl-lower alkyl group, an arylsulfonylamino group, an aryl-lower alkyl group, and a heterocyclic group; R7 represents a lower alkyl group or a lower cycloalkyl group; R11 represents a substitutent of a formula:   in which R12 represents an alkyl group having up to 8 carbon atoms, a halo-lower alkyl group, an aryl-lower alkyl group, a hydroxy-lower alkyl group, a tri-lower alkylsilyl-lower alkyl group, a lower alkoxy-lower alkyl group, a lower alkylthio-lower alkyl group, a heterocyclic group, or an aryl group; said aryl group may be substituted by a halogen atom, a lower alkyl group, a halo-lower alkyl group, a lower alkoxy group, or a nitro group; or R11 may be bonded to the skeleton via a lower alkylene or alkenylene group; R4' represents a hydrocarbon group or a halogenated hydrocarbon group; and n means an integer from 0 to 3, provided that a number of carbon atoms of a lower alkyl group, a lower alkoxy group, a lower alkylene group and a lower alkenylene group is 1-6, if otherwise is not specified; a number of carbon atoms of lower cycloalkyl group is 3-7; an aryl group is a phenyl or a naphthyl group; and a heterocyclic group is a 3-12-membered ring, comprising hetero atoms, selected from the group consisting of oxygen, sulfur and nitrogen atoms. 2. Use of a compound of the following formula:   wherein R6 represents an aryl-lower alkyl group or an aryl-lower alkyl group substituted by one or two substituents selected from a halogen atom, a haloaryl group, a lower alkyl group, a halo-lower alkyl group, a lower alkoxy group, a nitro group, an amino group, a cyano group, an aryl group, a cyanoaryl group, an aryl-lower alkyloxy group, an arylsulfonyl-lower alkyl group, an arylsulfonylamino group, an aryl-lower alkyl group, and a heterocyclic group; R7 represents a lower alkyl group or a lower cycloalkyl group; R11 represents a substitutent of a formula:   in which R12 represents an alkyl group having up to 8 carbon atoms, a halo-lower alkyl group, an aryl-lower alkyl group, a hydroxy-lower alkyl group, a tri-lower alkylsilyl-lower alkyl group, a lower alkoxy-lower alkyl group, a lower alkylthio-lower alkyl group, a heterocyclic group, or an aryl group; said aryl group may be substituted by a halogen atom, a lower alkyl group, a halo-lower alkyl group, a lower alkoxy group, or a nitro group; or R11 may be bonded to the skeleton via a lower alkylene or alkenylene group; R4' represents a hydrocarbon group or a halogenated hydrocarbon group; and n means an integer from 0 to 3, provided that a number of carbon atoms of a lower alkyl group, a lower alkoxy group, a lower alkylene group and a lower alkenylene group is 1-6, if otherwise is not specified; a number of carbon atoms of lower cycloalkyl group is 3-7; an aryl group is a phenyl or a naphthyl group; and a heterocyclic group is a 3-12-membered ring, comprising hetero atoms, selected from the group consisting of oxygen, sulfur and nitrogen atoms, or its pharmaceutically acceptable salt for preparing a pharmaceutical composition for preventing and treating impaired glucose tolerance, diabetes, diabetic complications, syndrome of insulin resistance, hyperlipidemia, atherosclerosis, cardiovascular disorders, hyperglycemia or hypertension; or stenocardia, hypertension, pulmonary hypertension, congestive heart failure, glomerulopathy, tubulointerstitial disorders, renal failure, atherosclerosis, angiostenosis, distal angiopathy, cerebral apoplexy, chronic reversible obstructions, allergic rhinitis, urticaria, glaucoma, diseases characterized by enteromotility disorders, impotence, diabetic complications, nephritis, cancerous cachexia, or restenosis after PTCA. 3. A method for preventing or treating impaired glucose tolerance, diabetes, diabetic complications, syndrome of insulin resistance, hyperlipidemia, atherosclerosis, cardiovascular disorders, hyperglycemia or hypertension; or stenocardia, hypertension, pulmonary hypertension, congestive heart failure, glomerulopathy, tubulointerstitial disorders, renal failure, atherosclerosis, angiostenosis, distal angiopathy, cerebral apoplexy, chronic reversible obstructions, allergic rhinitis, urticaria, glaucoma, diseases characterized by enteromotility disorders, impotence, diabetic complications, nephritis, cancerous cachexia, or restenosis after PTCA, which comprises administering a compound of the following formula:   wherein R6 represents an aryl-lower alkyl group or an aryl-lower alkyl group substituted by one or two substituents selected from a halogen atom, a haloaryl group, a lower alkyl group, a halo-lower alkyl group, a lower alkoxy group, a nitro group, an amino group, a cyano group, an aryl group, a cyanoaryl group, an aryl-lower alkyloxy group, an arylsulfonyl-lower alkyl group, an arylsulfonylamino group, an aryl-lower alkyl group, and a heterocyclic group; R7 represents a lower alkyl group or a lower cycloalkyl group; R11 represents a substitutent of a formula:   in which R12 represents an alkyl group having up to 8 carbon atoms, a halo-lower alkyl group, an aryl-lower alkyl group, a hydroxy-lower alkyl group, a tri-lower alkylsilyl-lower alkyl group, a lower alkoxy-lower alkyl group, a lower alkylthio-lower alkyl group, a heterocyclic group, or an aryl group; said aryl group may be substituted by a halogen atom, a lower alkyl group, a halo-lower alkyl group, a lower alkoxy group, or a nitro group; or R11 may be bonded to the skeleton via a lower alkylene or alkenylene group; R4' represents a hydrocarbon group or a halogenated hydrocarbon group; and n means an integer from 0 to 3, provided that a number of carbon atoms of a lower alkyl group, a lower alkoxy group, a lower alkylene group and a lower alkenylene group is 1-6, if otherwise is not specified; a number of carbon atoms of lower cycloalkyl group is 3-7; an aryl group is a phenyl or a naphthyl group; and a heterocyclic group is a 3-12-membered ring, comprising hetero atoms, selected from the group consisting of oxygen, sulfur and nitrogen atoms, or its pharmaceutically acceptable salt. 4. A method for preventing or treating impaired glucose tolerance, diabetes, diabetic complications, syndrome of insulin resistance, hyperlipidemia, atherosclerosis, cardiovascular disorders, hyperglycemia or hypertension; or stenocardia, hypertension, pulmonary hypertension, congestive heart failure, glomerulopathy, tubulointerstitial disorders, renal failure, atherosclerosis, angiostenosis, distal angiopathy, cerebral apoplexy, chronic reversible obstructions, allergic rhinitis, urticaria, glaucoma, diseases characterized by enteromotility disorders, impotence, diabetic complications, nephritis, cancerous cachexia, or restenosis after PTCA, which comprises, as an active ingredient, a compound of the following formula:   wherein R13 represents an aryl-lower alkyl group or an aryl-lower alkyl group substituted by one or two substituents selected from a halogen atom, a lower alkyl group, a halo-lower alkyl group, a lower alkoxy group, a nitro group, an amino group, a cyano group, an aryl group, a haloaryl group, a cyanoaryl group, an aryl-lower alkyl group, an arylsulfonyl-lower alkyl group, an arylsulfonylamino group, and a heterocyclic group; R14 represents a lower alkyl group; R15 represents a substitutent of a formula:   in which R16 represents a lower alkyl group or an aryl group; R4' represents a hydrocarbon group or a halogenated hydrocarbon group; and n means an integer from 0 to 3, provided that a number of carbon atoms of a lower alkyl group, a lower alkoxy group, a lower alkylene group and a lower alkenylene group is 1-6, an aryl group is a phenyl or a naphthyl group; and a heterocyclic group is a 3-12-membered ring, comprising hetero atoms, selected from the group consisting of oxygen, sulfur and nitrogen atoms, or a pharmaceutically acceptable salt thereof. 5. Use of a compound of thr following formula   wherein R13 represents an aryl-lower alkyl group or an aryl-lower alkyl group substituted by one or two substituents selected from a halogen atom, a lower alkyl group, a halo-lower alkyl group, a lower alkoxy group, a nitro group, an amino group, a cyano group, an aryl group, a haloaryl group, a cyanoaryl group, an aryl-lower alkyl group, an arylsulfonyl-lower alkyl group, an arylsulfonylamino group, and a heterocyclic group; R14 represents a lower alkyl group; R15 represents a substitutent of a formula:   in which R16 represents a lower alkyl group or an aryl group; R4' represents a hydrocarbon group or a halogenated hydrocarbon group; and n means an integer from 0 to 3, provided that a number of carbon atoms of a lower alkyl group, a lower alkoxy group, a lower alkylene group and a lower alkenylene group is 1-6, ian aryl group is a phenyl or a naphthyl group; and a heterocyclic group is a 3-12-membered ring, comprising hetero atoms, selected from the group consistin