Pharmaceutical composition for treatment of disease due to vascular constriction or vasodilation

摘要

A therapeutic and/or preventing agent for a disease due to vascular constriction or vasodilation comprising a EDG-5 modulator. Since EDG-5 modulator specifically binds EDG-5 and shows antagonistic or agonistic action, EDG-5 antagonist is useful for treating and/or preventing for a disease due to vascular constriction, for example, cerebrovascular spasmodic disorder after subarachnoid hemorrhage or stroke, cardiovasucular spasmodic disorder, hypertension, renal disease, cardiac infarction, cardiac angina, arrhythmia, facilitation of the portal blood pressure involved in liver cirrhosis, varicosity involved in liver cirrhosis and the like, or EDG-5 agonist is useful for treating and/or preventing for a disease due to vasodilation of blood vessels, for example, chronic headache (such as migraine, tension-type headache, mixed-type headache thereof, or migrainous neuralgia), haemorrhoid, congestive disorder and the like.

主权项

1. A compound represented by formula (I):
A-X—Y—Z—B  (I) wherein: A represents wherein R1 represents (1) benzene or pyridine optionally substituted with (1) halogen, (2) alkyl, (3) halo alkyl, or (4) alkoxy; (2) C1-6 alkyl optionally substituted with (1) C1-4 alkylthio, (2) C3-7 cycloalkyl, or (3) heterocycl; (3) C3-7 cycloalkyl; and (4) naphthyl, R2 represents hydroxy or C1-6 alkoxy, R3 is absent, and r represents 0, X represents a single bond, Y represents —CO—, Z represents a nitrogen atom optionally substituted with C1-6 alkyl, B represents benzene, or pyridine, optionally with 1-5 substituent(s) selected from (1) alkyl optionally substituted with halogen atom, (2) alkenyl optionally with a substituent(s), (3) alkynyl optionally with a substituent(s), (4) carbocyclic ring optionally with a substituent(s), (5) heterocyclic ring optionally with a substituent(s), (6) hydroxyl optionally with a substituent(s), (7) thiol optionally with a substituent(s), (8) amino optionally with a substituent(s), (9) carbamoyl optionally with a substituent(s), (10) sulfamoyl optionally with a substituent(s), (11) carboxyl, (12) alkoxycarbonyl, (13) sulfo, (14) sulfino, (15) phosphono, (16) nitro, (17) cyano, (18) amidino, (19) imino, (20) —B(OH)2, (21) halogen atom, (22) alkysulfinyl, (23) aromatic ring sulfinyl, (24) alkylsulfonyl, (25) aromatic ring sulfonyl, (26) acyl, (27) oxo, (28) thioxo, and (29) (C1-6 alkoxyimino) methyl,with proviso that B represents neither 3-(2-diisopropylamino)ethoxy-4-methoxyphenyl group, 1-isopropyl-4-(2-methoxyphenyl)piperidine group, an unsubstituted benzene group, nor a benzene substituted with a halogen atom when R1 is a benzene,or a pharmaceutically acceptable salt thereof.