Sulfonamides

A compound of the formula ##STR13## wherein R.sup.1 is hydrogen, lower-alkyl, lower alkoxy, lower-alkylthio, halogen or trifluoromethyl;

• R.sup.2 is hydrogen, halogen, lower-alkoxy, trifluoromethyl or --OCH.sub.2 COOR.sup.a ;
• and
• R.sup.3 is hydrogen, halogen, lower-alkyl, lower-alkylthio, trifluoromethyl, C.sub.3 -C.sub.8 cycloalkyl, lower-alkoxy or trifluoromethoxy;
• or
• R.sup.2 and R.sup.3 together signify butadienyl, methylenedioxy, ethylenedioxy or isopropylidenedioxy;
• R.sup.4 is hydrogen, lower-alkyl, C.sub.3 -C.sub.8 cycloalkyl, trifluoromethyl, lower-alkoxy, lower alkylthio, lower-alkylthio-lower-alkyl, hydroxy-lower-alkyl, hydroxy-lower alkoxy, lower-alkoxy-lower alkyl, hydroxy-lower-alkoxy-lower-alkyl, hydroxy-lower-alkoxy-lower-alkoxy, lower-alkylsulphinyl, lower-alkylsulphonyl, 2-methoxy-3-hydroxypropoxy, 2-hydroxy-3-phenylpropyl, amino-lower alkyl, lower-alkylamino-lower-alkyl, di-lower-alkylamino-lower-alkyl, amino, lower-alkylamino, di-lower-alkylamino, unsubstituted phenyl amino, phenylamino substituted with halogen, lower-alkyl, lower alkoxycarboxyl or trifluoromethyl, unsubstituted phenyl, phenyl substituted with halogen, lower alkyl, lower-alkoxy-carboxyl or trifluoromethyl, unsubstituted phenylthio, phenylthio substituted with halogen, lower-alkyl, lower alkoxy carboxyl or trifluoromethyl, unsubstituted phenoxy, phenoxy substituted with halogen, lower alkyl, lower-alkoxy-carboxyl or trifluoromethyl, unsubstituted phenyl-lower alkyl, phenyl-lower-alkyl substituted with halogen, lower-alkyl, lower-alkoxy-carboxyl or trifluoromethyl, unsubstituted heterocyclyl selected from 2-furyl, 3-furyl, pyrimidyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyridyl N-oxide, 1,2-diazinyl, 1,4-diazinyl, morpholino, 2-thienyl, 3-thienyl, isoxazolyl, oxazolyl, imidazolyl, pyrrolyl, benzofuranyl, benzothienyl, indolyl, purinyl, quinolyl, isoquinolyl and quinazolyl or heterocyclyl as defined above substituted by lower alkyl, lower alkoxy, halogen, phenyl or phenyl-lower alkyl;
• R.sup.5 is hydrogen, lower-alkyl, lower alkanoyl, benzoyl, heterocyclylcarbonyl wherein the heterocyclyl is selected from unsubstituted 2-furyl, 3-furyl, pyrimidyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyridyl N-oxide, 1,2-diazinyl, 1,4-diazinyl, morpholino, 2-thienyl, 3-thienyl, isoxazolyl, oxazolyl, imidazolyl, pyrrolyl, benzofuranyl, benzothienyl, indolyl, purinyl, quinolyl, isoquinolyl and quinazolyl or heterocyclyl as defined above substituted by lower alkyl, lower alkoxy, halogen, phenyl, phenyl-lower alkyl, heterocyclyl methyl wherein the heterocyclyl is selected from 2-furyl, 3-furyl, pyrimidyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyridyl N-oxide, 1,2-diazinyl, 1,4-diazinyl, morpholino, 2-thienyl, 3-thienyl, isoxazolyl, oxazolyl, imidazolyl, pyrrolyl, benzofuranyl, benzothienyl, indolyl, purinyl, quinolyl, isoquinolyl and quinazolyl or heterocyclyl as defined above substituted by lower alkyl, lower alkoxy, halogen, phenyl or phenyl-lower alkyl, or tetrahydropyran-2-yl;
• Z is --O--, --S--, vinylene, --CO--, OCHR.sup.10 -- or --SCHR.sup.10 ;
• R.sup.10 is hydrogen or lower-alkyl;
• R.sup.a and R.sup.b each independently are hydrogen or lower-alkyl;
• and
• n is 1, 2 or 3.

A pharmaceutical composition comprising a compound of the formula ##STR14## wherein R.sup.1 is hydrogen, lower-alkyl, lower alkoxy, lower-alkylthio, halogen or trifluoromethyl;

• R.sup.2 is hydrogen, halogen, lower-alkoxy, trifluoromethyl or --OCH.sub.2 COOR.sup.a ;
• and
• R.sup.3 is hydrogen, halogen, lower-alkyl, lower-alkylthio, trifluoromethyl, C.sub.3 -C.sub.8 cycloalkyl, lower-alkoxy or trifluoromethoxy;
• or
• R.sup.2 and R.sup.3 together are butadienyl, methylenedioxy, ethylenedioxy or isopropylidenedioxy;
• R.sup.4 is hydrogen, lower-alkyl, C.sub.3 -C.sub.8 cycloalkyl, trifluoromethyl, lower-alkoxy, lower alkylthio, lower-alkylthio-lower-alkyl, hydroxy-lower-alkyl, hydroxy-lower alkoxy, lower-alkoxy-lower alkyl, hydroxy-lower-alkoxy-lower-alkyl, hydroxy-lower-alkoxy-lower-alkoxy, lower-alkylsulphinyl, lower-alkylsulphonyl, 2-methoxy-3-hydroxyproxy, 2-hydroxy-3-phenylpropyl, amino-lower alkyl, lower-alkylamino-lower-alkyl, di-lower-alkylamino-lower-alkyl, amino, lower-alkylamino, di-lower-alkylamino, unsubstituted phenyl amino, phenylamino substituted with halogen, lower-alkyl, lower alkoxycarboxyl or trifluoromethyl, unsubstituted phenyl, phenyl substituted with halogen, lower alkyl, lower-alkoxy-carboxyl or trifluoromethyl, unsubstituted phenylthio, phenylthio substituted with halogen, lower-alkyl, lower alkoxy carboxyl or trifluoromethyl, unsubstituted phenoxy, phenoxy substituted with halogen, lower alkyl, lower-alkoxy-carboxyl or trifluoromethyl, unsubstituted phenyl-lower alkyl, phenyl-lower-alkyl substituted with halogen, lower-alkyl, lower-alkoxy-carboxyl or trifluoromethyl, unsubstituted heterocyclyl selected from 2-furyl, 3-furyl, pyrimidyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyridyl N-oxide, 1,2-diazinyl, 1,4-diazinyl, morpholino, 2-thienyl, 3-thienyl, isoxazolyl, oxazolyl, imidazolyl, pyrrolyl, benzofuranyl, benzothienyl, indolyl, purinyl, quinolyl, isoquinolyl and quinazolyl or heterocyclyl as defined above substituted by lower alkyl, lower alkoxy, halogen, phenyl or phenyl-lower alkyl;
• R.sup.5 is hydrogen, lower-alkyl, lower alkanoyl, benzoyl, heterocyclylcarbonyl wherein the heterocyclyl is selected from unsubstituted 2-furyl, 3-furyl, pyrimidyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyridyl N-oxide, 1,2-diazinyl, 1,4-diazinyl, morpholino, 2-thienyl, 3-thienyl, isoxazolyl, oxazolyl, imidazolyl, pyrrolyl, benzofuranyl, benzothienyl, indolyl, purinyl, quinolyl, isoquinolyl and quinazolyl or heterocyclyl as defined above substituted by lower alkyl, lower alkoxy, halogen, phenyl, phenyl-lower alkyl, heterocyclyl methyl wherein the heterocyclyl is selected from 2-furyl, 3-furyl, pyrimidyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyridyl N-oxide, 1,2-diazinyl, 1,4-diazinyl, morpholino, 2-thienyl, 3-thienyl, isoxazolyl, oxazolyl, imidazolyl, pyrrolyl, benzofuranyl, benzothienyl, indolyl, purinyl, quinolyl, isoquinolyl and quinazolyl or heterocyclyl as defined above substituted by lower alkyl, lower alkoxy, halogen, phenyl or phenyl-lower alkyl, or tetrahydropyran-2-yl;
• R.sup.6 to R.sup.9 are hydrogen, halogen, trifluoromethyl, lower-alkyl, lower-alkoxy, lower-alkylthio, hydroxy, hydroxymethyl, cyano, carboxyl, formyl, methylsulphinyl, methylsulphonyl, methylsulphonyloxy or lower-alkyloxy-carboyloxy;
• or
• R.sup.7 together with R.sup.6 or R.sup.8 signify butadienyl, methylenedioxy, ethylenedioxy or isopropylidenedioxy;
• is --O--, --S--, vinylene, --CO--, OCHR.sup.10 -- or --SCHR.sup.10 ;
• R.sup.10 is hydrogen or lower alkyl;
• X and Y each independently are O, S or NH;
• or YR.sup.5 is lower-alkylsulphinyl;
• R.sup.a, R.sup.b, R.sup.c and R.sup.d each independently are hydrogen or lower-alkyl;
• or R.sup.c and R.sup.d together signify methylene, ethylene or isopropylidene;
• and
• n is 1, 2 or 3
• or a stereoisomer or salt thereof and an inert carrier.

A method of treating disorders associated with endothelin activities comprising administering to a host in need of such treatment an effective amount of a compound of the formula ##STR15## wherein R.sup.1 is hydrogen, lower-alkyl, lower alkoxy, lower-alkylthio, halogen or trifluoromethyl;

• R.sup.2 is hydrogen, halogen, lower-alkoxy, trifluoromethyl or --OCH.sub.2 COOR.sup.a ;
• R.sup.3 is hydrogen, halogen, lower-alkyl, lower-alkylthio, trifluoromethyl, C.sub.3 -C.sub.8 cycloalkyl, lower-alkoxy or trifluoromethoxy;
• or
• R.sup.2 and R.sup.3 together signify butadienyl, methylenedioxy, ethylenedioxy or isopropylidenedioxy;
• R.sup.4 is hydrogen, lower-alkyl, C.sub.3 -C.sub.8 cycloalkyl, trifluoromethyl, lower-alkoxy, lower alkylthio, lower-alkylthio-lower-alkyl, hydroxy-lower-alkyl, hydroxy-lower alkoxy, lower-alkoxy-lower alkyl, hydroxy-lower-alkoxy-lower-alkyl, hydroxy-lower-alkoxy-lower-alkoxy, lower-alkylsulphinyl, lower-alkylsulphonyl, 2-methoxy-3-hydroxypropoxy, 2-hydroxy-3-phenylpropyl, amino-lower-alkyl, lower-alkylamino-lower-alkyl, di-lower-alkylamino-lower-alkyl, amino, lower-alkylamino, di-lower-alkylamino, unsubstituted phenyl amino, phenylamino substituted with halogen, lower-alkyl, lower alkoxy-carboxyl or trifluoromethyl, unsubstituted phenyl, phenyl substituted with halogen, lower alkyl, lower-alkoxy-carboxyl or trifluoromethyl, unsubstituted phenylthio, phenylthio substituted with halogen, lower-alkyl, lower alkoxy carboxyl or trifluoromethyl, unsubstituted phenoxy, phenoxy substituted with halogen, lower alkyl, lower-alkoxy-carboxyl or trifluoromethyl, unsubstituted phenyl-lower alkyl, phenyl-lower-alkyl substituted with halogen, lower-alkyl, lower-alkoxy-carboxyl or trifluoromethyl, unsubstituted heterocyclyl selected from 2-furyl, 3-furyl, pyrimidyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyridyl N-oxide, 1,2-diazinyl, 1,4-diazinyl, morpholino, 2-thienyl, 3-thienyl, isoxazolyl, oxazolyl, imidazolyl, pyrrolyl, benzofuranyl, benzothienyl, indolyl, purinyl, quinolyl, isoquinolyl and quinazolyl or heterocyclyl as defined above substituted by lower alkyl, lower alkoxy, halogen, phenyl or phenyl-lower alkyl;
• R.sup.5 is hydrogen, lower-alkyl, lower-alkanoyl, benzoyl, heterocyclylcarbonyl wherein the heterocyclyl is selected from unsubstituted 2-furyl, 3-furyl, pyrimidyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyridyl N-oxide, 1,2-diazinyl, 1,4-diazinyl, morpholino, 2-thienyl, 3-thienyl, isoxazolyl, oxazolyl, imidazolyl, pyrrolyl, benzofuranyl, benzothienyl, indolyl, purinyl, quinolyl, isoquinolyl and quinazolyl or heterocyclyl as defined above substituted by lower alkyl, lower alkoxy, halogen, phenyl, phenyl-lower alkyl, heterocyclyl methyl wherein the heterocyclyl is selected from 2-furyl, 3-furyl, pyrimidyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyridyl N-oxide, 1,2-diazinyl, 1,4-diazinyl, morpholino, 2-thienyl, 3-thienyl, isoxazolyl, oxazolyl, imidazolyl, pyrrolyl, benzofuranyl, benzothienyl, indolyl, purinyl, quinolyl, isoquinolyl and quinazolyl or heterocyclyl as defined above substituted by lower alkyl, lower alkoxy, halogen, phenyl or phenyl-lower alkyl, or tetrahydro-pyran-2-yl;
• R.sup.6 to R.sup.9 are hydrogen, halogen, trifluoromethyl, lower-alkyl, lower-alkoxy, lower-alkylthio, hydroxy, hydroxymethyl, cyano, carboxyl, formyl, methylsulphinyl, methylsulphonyl, methylsulphonyloxy or lower-alkyloxycarbonyloxy;
• or
• R.sup.7 together with R.sup.6 or R.sup.8 signify butadienyl, methylenedioxy, ethylenedioxy or isopropylidenedioxy;
• is --O--, --S--, vinylene, --CO--, OCHR.sup.10 -- or --SCHR.sup.10 ;
• R.sup.10 is hydrogen or lower-alkyl;
• X and Y each independently are O, S or NH;
• or YR.sup.5 is lower-alkylsulphinyl;
• R.sup.a, R.sup.b, R.sup.c and R.sup.d each independently are hydrogen or lower-alkyl;
• or R.sup.c and R.sup.d together signify methylene, ethylene or isopropylidene;
• and
• n is 1, 2 or 3
• or a stereoisomer or salt thereof.

A compound of the formula ##STR16## wherein R.sup.1 is hydrogen;

• R.sup.2 is hydrogen;
• R.sup.3 is lower alkyl;
• R.sup.4 is hydrogen, lower-alkyl, 2-thienyl, 3-thienyl or 3-furyl;
• R.sup.6 is lower-alkoxy;
• R.sup.7 to R.sup.9 are hydrogen;
• R.sup.11 is halogen
• Z is --O--
• W is 1,3-dioxolan-4-ylmethoxy, 2,2-dimethyl-1,3-dioxolan-4-ylmethoxy or 2,3-dihydroxy-propoxy
• or a stereiosomer or salt thereof.