Patent IL-122464-A (IL)
Title: N-pyrazine-pyridinesulfonamide derivatives, process for their preparation and pharmaceutical compositions containing them
IPC: A61P9/00
Filed: 1996-06-03
Abstract: Endothelin receptor antagonist compounds of the formula wherein one of A1, A2, A3 and A4 is nitrogen and the remainder of A1, A2, A3 and A4 are CH; Ar is a phenyl group which is unsubstituted or bears 1,2 or 3 substituents independently selected from (1-6C) alkyl, amino (1-6C) alkyl, hydroxy (1-6C) alkyl, N-[(1-4C) alkyl] amino (1-6C) alkyl, N,N-[ di(1-4C) alkyl] amino (1-6C) alkyl, carboxyl (1-6C) alkyl, (1-6C) alkoxycarbonyl (1-6C) alkyl, (1-6C) alkylcarbonyloxy (1-6C) alkyl, carbamoyl (1-6C) alkyl, N- (1-6C) alkylcarbamoyl (1-6C) alkyl, di-N- (1-6C) alkylcarbamoyl 1093 י" ב בסיון התשס" ב - May 23, 2002 (1-6C) alkyl, N-(1-6C) alkylcarbamoyloxy (1-6C) alkyl, carboxy (1-6C) alkoxy, carboxy (1-6C) alkylthio, (1-6C) alkoxycarbonyl (1-6C) alkoxy, (1-6C) alkoxycarbonyl (1-6C) alkylthio, carbamoyl (1-6C) alkoxy, (1-6C) alkylcarbamoyl (1-6C) alkoxy, di (1-6C) alkylcarbonyl (1-6C) alkoxy, carbamoyl (1-6C) alkylthio, (1-6C) alkylcarbamoyl (1-6C) alkylthio, di alkylcarbamoyl (1-6C) alkylthio, (2-6C) alkenyl, carboxy (2-6C) alkenyl, (2-6C) alkynyl, carboxyl (2-6C) alkynyl, halogeno (2-6C) alkyl, trifluoromethyl, trichloromethyl, tribromomethyl, (1-6C) alkoxy, hydroxy (1-6C) alkoxy, dihalogeno (1-6C) alkoxy, trihalogeno (1-6C) alkoxy, (2-6C) alkenyloxy (1-6C) alkyl, (2-6C) alkenyloxy, (1-4C) alkoxy (1-6C) alkyl, (1-6C) alkoxycarbonyl (1-6C) alkoxy (1-6C) alkyl, carboxy (1-6C) alkoxy (1-6C) alkyl, hydroxy(1-6C) alkoxy (1-6C) alkyl, (1-6C) alkylthio (1-6C) alkyl, (1-4C) alkylsulphinyl (1-6C) alkyl, (1-4C) alkylsulphonyl (1-6C) alkyl, (1-4C) alkylenedioxy, (3-6C) cycloalkyl, (3-8C) cycloalkyl (1-6C) alkyl, phenyl, phenyl (1-6C) alkyl, phenoxy, phenyl (1-6C) alkoxy, pyridyl (1-6C) alkoxy (1-6C) alkyl, halogeno, hydroxy, mercapto, cyano, nitro, carboxy, (1-6C) alkoxycarbonyl, (2-6C) alkenyloxycarbonyl, phenyloxycarbonyl, phenyl (1-6C) alkoxycarbonyl, (1-6C) alkanoyl, benzoyl, (1-6C) alkylthio, (1-6C) alkylsulphinyl (1-6C) alkylsulphonyl, phenylthio, phenylsulphinyl, phenylsulphonyl, (1-6C) alkanoylamino, trifluoroacetyl, trifluoroacetamido, N-[(1-4C) alkyl] trifluoroacetamido, benzamido, N-[(1-4C) alkyl] benzamido, carbamoyl, (1-4C) alkylcarbamoyl, di(1-4C) alkylcarbamoyl, phenylcarbamoyl, sulphamoyl, N-(1-4C) alkylsulphamoyl, N,N-di (1-4C) alkylsulphamoyl, N-phenylsulphamoyl, (1-6C) alkanesulphonamido, benzenesulphonamido, ureido, 3-(1-6C) alkylureido, 3-phenylureido, thioureido, 3-(1-6C) alkylthioureido, 3-phenylthioureido, a five membered heterocyclyl group containing 1,2,3 or 4 heteroatoms independently selected from nitrogen, oxygen and sulphur, a six membered heterocyclyl group containing 1, 2 or 3 heteroatoms independently selected from nitrogen, oxygen and sulphur, and a group =NRaRb in which Ra and Rb are independently selected from hydrogen, (1-6C) alkyl, phenyl (1-4C) alkyl and (1-6C) alkyl bearing a carboxy, (1-6C) alkoxycarbonyl, carbamoyl, (1-6C) alkylcarbamoyl or di (1-6C) alkylcarbamoyl group, or the group -NRaRb taken together complete a 1-pyrrolidinyl, 2-oxo-1-pyrrolidinyl, 1-piperidinyl, 2-oxo-1-piperidinyl, morpholino or thiomorpholino ring; B1 is an optional substituent on a carbon atom of A1, A2, A3 or A4 selected from (1-4C) alkyl, halogeno and (1-4C) alkoxy; m is zero, 1, 2 or 3; Ry is hydrogen, halogeno, (1-4C) alkyl, (1-4C) alkoxy or trifluoromethoxy; R1 is hydrogen, halogeno, (1-4C) alkyl, methoxy, ethoxy, trifluoromethyl or ethynyl; and wherein any of said phenyl or benzene or heterocyclyl moieties of a substituent on Ar may be unsubstituted or bear one or two substituents independently selected from (1-4C) alkyl, (1-4C) alkoxy, halogeno, cyano, carboxy and trifluoromethyl; or an N-oxide thereof; or a pharmaceutically-acceptable salt thereof; or a prodrug thereof.