Patent TW-401402-B (TW)
Title: Novel N-heterocyclyl sulfonamides and pharmaceutical composition and preparation process thereof
Inventor: BRADBURY ROBERT HUGH
IPC: C07D241/22
Filed: 1995-03-30
Granted: 2000-08-11
Abstract: The invention concerns pharmaceuticaly useful compounds of the formula I, in which Q, A1, A2, A3, W, X, Y, Z and R1 have any of the meanings defined herein, and their pharmaceutically acceptable salts, and pharmaceutically compositions containing them. The novel compounds possess endothelin receptor antagonist activity and are useful in the treatment of diseases or medical conditions in which elevated or abnormal levels of endothelin play a significant causative role. The invention further concerns processes for the manufacture of the novel compounds and the use of the compounds in medical treatment. A nitrogen derivative of the formula I wherein Q is a naphthyl or biphenyl group; A1, A2 and A3 are attached to a phenyl or benzene ring of Q and are independently selected from hydrogen, (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, (2-6C) alkenyl, (2-6C) alkynyl, halogeno (1-6C) alkyl, (1-6C) alkoxy, dihalogeno (1-6C) alkoxy, trihalogeno (1-6C) alkoxy, (2-6C) alkenyloxy, (1-4C) alkoxy (1-6C) alkyl, (1-4C) 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, 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, benezenesulphonamido, ureido, 3-( 1-6C) alkylureido, 3-phenylureido, thioureido, 3-(1-6C) alkylthioureido, 3-phenylthioureido 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 or (1-4C) alkoxycarbonyl group, or the group -NRaRb taken together complete a 1-pyrrolidinyl, 2-oxo-1-pyrrolidinyl, 1-piperidinyl or 2-oxo-1-piperidinyl ring; W, X, Y and Z are independently selected from nitrogen and CR2 such that two or three of W, X, Y and Z are nitrogen and the remainder are CR2 or X is nitrogen and W, Y and Z are CR2; R2 has any of the values defined above for A1, A2 or A3; R1 is 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, (2-6C) alkenyl, 2-[(1-6C) alkoxycarbonyl] ethenyl, 2-phenylethenyl, (2-6C) alkynyl, (1-6C) alkoxycarbonylethynyl, phenylethynyl, halogeno (1-6C) alkyl, (1-3C) alkoxy, dihalogeno (1-3C) alkoxy, trihalogeno (1-3C) alkoxy, (2-6C) alkenyloxy, (1-4C) alkoxy (1-6C) alkyl, (1-4C) alkylthio (1-6C) alkyl, (1-4C) alkylsulphinyl (1-6C) alkyl, (1-4C) alkylsulphonyl (1-6C) alkyl, (3-6C) cycloalkyl, (3-8C) cycloalkyl (1-6C) alkyl, phenyl (1-6C) alkyl, pheyl (1-3C) alkoxy, halogeno, hydroxy, mercapto, 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, benezenesulphonamido, ureido, 3- (1-6C) alkylureido, 3-phenylureido, thioureido, 3-(1-6C) alkylthioureido, 3-phenylthioureido 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 or (1-4C) alkoxycarbonyl group, or the group -NRaRb taken together complete a 1-pyrrolidinyl, 2-oxo-1-pyrrolidinyl, 1-piperidinyl or 2-oxo-1-piperidinyl ring; or when X or Y is CR2, R1 together with the adjacent R2 is (3-5C) alkylene or (3-5C) alkenylene which together with the carbon atoms to which R1 and the adjacent R2 are attached complete a 5-7 membered ring; and wherein any of said phenyl, naphthyl or benzene moieties of A1, A2, A3, R1 or R2 may be unsubstituted or bear one or two substituents independently selected from (1-4C) alkyl, (1-4C) alkoxy, halogeno, cyano and trifluoromethyl; or a pharmaceutically-acceptable salt thereof.