NOVEL HETEROCYCLIC AMIDE COMPOUNDS AND MEDICINAL USES THEREOF

• Main Authors: AKAHOSHI FUMIHIKO, SAKASHITA HIROSHI, NAKAJIMA MASAHIDE, IMADA TERUAKI, EDA MASAHIRO, ASHIMORI ATSUYUKI, YOSHIMURA TAKUYA
• Format: Patent
• Language: English
• Published: 25.08.2000
• Edition: 7
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PEPTIDES; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES

PURPOSE: A heterocyclic amide compound and a pharmacologically acceptable salt thereof of the present invention have superior inhibitory action on chymase group in mammals inclusive of human, and can be administered orally or parenterally. Therefore, they are useful as chymase inhibitors and can be used for the prophylaxis and treatment of various diseases caused by chymase, such as those caused by angiotensin II. CONSTITUTION: In heterocyclic amide compound of the formula (I), R is a hydrogen atom, alkyl, -CHO, -CONH2, -COR1, -COOR1, -CONHOR1, -CONHR1, -CONR1R1', -CONHSO2R1, -COSR1, -COCOR2, -COCOOR2, -CONHCOOR2, -COCONR3R4, -CSXR1, -SO2WR1, -SO2NR1R1' or -SO2E wherein R1 and R1' may be the same or different and each is independently alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle or heterocyclic alkyl, R2, R3 and R4 may be the same or different and each is independently a hydrogen atom, alkyl or arylalkyl, or -NR3R4 may in combination form a heterocycle, X is a single bond, -NH-, -O- or -S-, W is a single bond, -NH-, -NHCO-, -NHCOO- or -NHCONH-, and E is a hydroxyl group or amino; R5, R6 and R7 may be the same or different and each is independently hydrogen atom or alkyl, or one of R5, R6 and R7 is aryl, arylalkyl, arylalkenyl, heteroaryl, heteroarylalkyl or heteroarylalkenyl and the rest is hydrogen atom; M is a carbon atom or nitrogen atom, provided that when M is a nitrogen atom, R6 is void; Y is cycloalkyl, aryl or heteroaryl; Z is a group of the formula (i), formula (ii), formula (iii), wherein R8 and R9 may be the same or different and each is independently hydrogen atom, alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, halogen, trifluoromethyl, cyano, nitro, -NR10R10', -NHSO2R10, -OR10, -COOR10, -CONHSO2R10 or -CONR10R10' wherein R10 and R10' may be the same or different and each is independently hydrogen atom, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl or trifluoromethyl, or -NR10R10' may in combination form heterocycle, A is -O-, -S- or -NR12- wherein R12 is a hydrogen atom, alkyl, cycloalkyl or cycloalkylalkyl, and a, b, c and d are each a carbon atom or one of them is a nitrogen atom and the rest is a carbon atom; and n is 0 or 1, wherein, of the above-mentioned groups, alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, arylalkenyl, heteroaryl, heteroarylalkyl, heteroarylalkenyl, heterocycle and heterocyclic alkyl each optionally has a substituent, or a pharmacologically acceptable salt thereof.