N-pyridazinyl-benzene (naphthalene-, biphenyl-) sulfonamide derivatives, their preparation and their use as endothelin antagonists

Claim 1

A compound of the formula or such a compound in pharmaceutically acceptable salt form, wherein: R is phenyl, naphthyl or biphenyl, each of which may be substituted with R¹, R² and R³; R¹, R² and R³ are each independently (a) hydrogen; (b) alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, aryloxy, aralkyl or aralkoxy, any of which may be substituted with Z¹, Z² and Z³; (c) halo; (d) hydroxyl; (e) cyano; (f) nitro; (g) -C(O)H or -C(O)R⁶; (h) -CO₂H or -CO₂R⁶; (i) -SH, -S(O) n R⁶, -S(O) m -OH, -S(O) m -OR⁶, O-S(O) m -R⁶ -O-S(O) m OH or -O-S(O) m -OR⁶; (j) -Z⁴-NR⁷R⁸; or (k) -Z⁴-N(R¹¹)-Z⁵-NR⁹R¹⁰; R⁴, R⁵ and R¹² are each independently (a) hydrogen; (b) alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, aryloxy, aralkyl or aralkoxy, any of which may be substituted with Z¹, Z² and Z³; (c) halo; (d) hydroxyl; (e) cyano; (f) nitro; (g) -C(O)H or -C(O)R⁶; (h) -CO₂H or -CO₂R⁶; (i) -SH, -S(O) n R⁶, -S(O) m -OH, -S(O) m -OR⁶, -O-S(O) m -R⁶, -O-S(O) m OH or -O-S(O) m -OR⁶; (j) -Z⁴-NR⁷R⁸; (k) -Z⁴-N(R¹¹)-Z⁵-NR⁹R¹⁰; or (l) R⁴ and R⁵, or R⁵ and R¹² together are alkylene or alkenylene (either of which may be substituted with Z¹, Z² and Z³), completing a 4- to 8-membered saturated, unsaturated or aromatic ring together with the carbon atoms to which they are attached; provided that when R is phenyl, at least two of R⁴, R⁵ and R¹² are other than hydrogen; R⁶ is alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl or aralkyl, any of which may be substituted with Z¹, Z² and Z³; R⁷ is (a) hydrogen; (b) alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl or aralkyl, any of which may be substituted with Z¹, Z² and Z³; (c) cyano; (d) hydroxyl; (e) -C(O)H or -C(O)R⁶; (f) -CO₂R⁶; or (g) -SH, -S(O) n R⁶, -S(O) m -OR⁶, -O-S(O) m -R⁶ or -O-S(O) m -OR⁶, except when Z⁴ is -S(O) n -; R⁸ is (a) hydrogen; (b) -C(O)H or -C(O)R⁶, except when Z⁴ is -C(O)- and R⁷ is -C(O)H, -C(O)R⁶ or -CO₂R⁶; or (c) alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl or aralkyl, any of which may be substituted with Z¹, Z² and Z³; or R⁷ and R⁸ together are alkylene or alkenylene (either of which may be substituted with Z¹, Z² and Z³), completing a 3- to 8- membered saturated, unsaturated or aromatic ring together with the nitrogen atom to which they are attached; R⁹ is (a) hydrogen; (b) hydroxyl; (c) -C(O)H or -C(O)R⁶; (d) -CO₂R⁶; (e) -SH, -S(O) n R⁶, -S(O) m -OR⁶, -O-S(O) m -R⁶ or -O-S(O) m -OR⁶; or (f) alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl or aralkyl, any of which may be substituted with Z¹, Z² and Z³; R¹⁰ is (a) hydrogen; (b) -C(O)H or -C(O)R⁶, except when Z⁵ is -C(O)- and R⁹ is -C(O)H, -C(O)R⁶ or -CO₂R⁶; or (c) alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl or aralkyl, any of which may be substituted with Z¹, Z² and Z³; R¹¹ is (a) hydrogen; (b) hydroxyl or -CO₂R⁶, except when one of R⁹ and R¹⁰ is hydroxyl or -CO₂R⁶; (c) -C(O)H or -C(O)R⁶; or (d) alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl or aralkyl, any of which may be substituted with Z¹, Z² and Z³; or any two of R⁹, R¹⁰ and R¹¹ together are alkylene or alkenylene (either of which may be substituted with Z¹, Z² and Z³), completing a 3- to 8-membered saturated, unsaturated or aromatic ring together with the atoms to which they are attached; Z¹, Z² and Z³ are each independently (a) hydrogen; (b) halo; (c) hydroxy; (d) alkyl, alkenyl, aralkyl, alkoxy, aryloxy or aralkoxy; (e) -SH, -S(O) n Z⁶, -S(O) m -OH, -S(O) m -OZ⁶, -O-S(O) m -Z⁶, -O-S(O) m OH or -O-S(O) m -OZ⁶; (f) oxo; (g) nitro; (h) cyano; (i) -C(O)H or -C(O)Z⁶; (j) -CO₂H or -CO₂Z⁶; or (k) -Z⁴-NZ⁷Z⁸, Z⁴-N(Z¹¹)-Z⁵Z⁶ or -Z⁴-N(Z¹¹)-Z⁵-NZ⁷Z⁸; Z⁴ and Z⁵ are each independently (a) a single bond; (b) -Z⁹-S(O) m -Z¹⁰; (c) -Z⁹-C(O)-Z¹⁰; (d) -Z⁹-C(S)-Z¹⁰; (e) -Z⁹-O-Z¹⁰; (f) -Z⁹-S-Z¹⁰; (g) -Z⁹-O-C(O)-Z¹⁰; or (h) alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl or aralkyl, any of which may be substituted with Z¹, Z² and Z³; Z⁶, Z⁷ and Z⁸ are each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, or aralkyl, or Z⁷ and Z⁸ together are alkylene or alkenylene, completing a 3- to 8-membered saturated, unsaturated or aromatic ring together with the nitrogen atom to which they are attached; Z⁹ and Z¹⁰ are each independently a single bond, alkylene, alkenylene or alkynylene, Z¹¹ is (a) hydrogen; (b) hydroxyl; (c) -C(O)H, -C(O)Z⁶ or -CO₂Z⁶, provided that when Z¹¹ is -CO₂Z⁶, Z⁶ is other than hydrogen; or (d) alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl or aralkyl; or any two of Z⁷, Z⁸ and Z¹¹ together are alkylene or alkenylene, completing a 3- to 8- membered saturated, unsaturated or aromatic ring together with the atoms to which they are attached; m is 1 or 2; and n is 0, 1 or 2.