Pfizer Corporation

Geoffrey N Thomas

Peter E Cross

John E Arrowsmith

Roger P Dickinson

Michael Snarey

John C Danielewicz

A series of novel N-alkyl N-(alkanesulphonamidoheterocyclicmethyl)-4-alkanesulphonamidophenethylamin es have been prepared, including their pharmaceutically acceptable salts and various key novel intermediates therefor. The heterocyclic moiety present in these compounds is a benzo-fused heterocyclic group derived from either benzofuran, benzothiophene, benzoxazole or quinoline, and it is attached to the adjacent methyl group of the molecule by means of the available ring carbon atom which is situated alpha to the hetero atom. These particular compounds are useful in therapy as highly effective anti-arrhythmic agents and therefore, are of value in the treatment of various cardiac arrhythmias. Preferred member compounds include N-methyl-N-(5 methanesulphonamidobenzofur-2-ylmethyl)-4-methanesulphonamidophenethylamin e and N-methyl-N-(6 methanesulphonamidoquinol-2-ylmethyl)-4-methanesulphonamidophenethylamine. Methods for preparing all these compounds from known starting materials are provided.

Benzoxazole sulfonamide anti-arrhythmic agents

A series of novel alkanesulphonamidophenyl-N-alkyl-N-(heterocyclic-alkyl)alkylamine derivatives have been prepared, including their pharmaceutically acceptable salts. These compounds are useful in therapy as anti-arrhythmic agents and therefore, are of value in the treatment of various cardiac arrhythmias. Said sulfonamide compounds are of the formula: ##STR1## wherein R and R.sup.1 are each C.sub.1 -C.sub.4 alkyl; X is --CH.sub.2 --, --CO-- or --CH(OH)--; n is two, three or four; and 'Het' is a nitrogen-containing heterocyclic group wherein said heterocyclic group is preferably 2H-3,4-dihydroisoquinol-1-on-2-yl or 2H-isoquinol-1-on-2-yl, each optionally substituted with halogen or C.sub.1 -C.sub.4 alkyl.

Isoquinolinylsulfonamides as anti-arrhythmic agents

A series of [N-alkyl-N-(nitro-, alkylsulphonamido, or amino-phenalkyl) amino]-alkyl, alkoxy or alkylthio phenyl derivatives having utility as anti-arrhythmic agents.

Anti-arrhythmic agents

A series of novel N-alkyl-N-(alkanesulphonamidoheterocyclicmethyl) -4-alkanesulphonamidophenethylamines have been prepared, including their pharmaceutically acceptable salts and various key novel intermediates therefor. The heterocyclic moiety present in these compounds is a benzo-fused heterocyclic group derived from either benzofuran, benzothiophene, benzoxazole or quinoline, and it is attached to the adjacent methyl group of the molecule by means of the available ring carbon atom which is situated alpha to the hetero atom. These particular compounds are useful in therapy as highly effective anti-arrhythmic agents and therefore, are of value in the treatment of various cardiac arrhythmias. Preferred member compounds include N-methyl-N-(5-methanesulphonamidobenzofur-2-ylmethyl)-4 -methanesulphonamidophenethylamine and N-methyl-N-(6- methanesulphonamidoquinol-2-ylmethyl)-4-methane-sulphonamidophenethylamine . Methods for preparing all these compounds from known starting materials are provided.

Quinolinyl sulfonamide anti-arrhythmic agents and use thereas

A series of novel alkanesulphonamidophenyl-N-alkyl-N-(heterocyclic-alkyl) alkylamine derivatives have been prepared, including their pharmaceutically acceptable salts. These compounds are useful in therapy as anti-arrhythmic agents and therefore, are of value in the treatment of various cardiac arrythmias. Said sulfonamide base compounds are of the formula: ##STR1## wherein R and R.sup.1 are each C.sub.1 -C.sub.4 alkyl; X is --CH.sub.2 --, --CO--or --CO(OH)--; n is two, three or four; and 'Het--' is a nitrogen-containing heterocyclic group wherein said heterocyclic group is phenyl or benzyl-substituted 2H-pyridazin-3-on-2-yl, or it is 2H-phthalazin-1-on-2-yl, 4-halo-2H-phthalizin-1-on-2-yl or 4-(C.sub.1 -C.sub.4 alkyl)-2H-phthalazin-1-on-2-yl, 2H-isoindolin-1-on-2-yl, 3H-quinazolin-4-on-3-yl, 2H-3,4-dihydroisoquinol-1-on-2-yl, 2H-isoquinol-on-2-yl, 1H-3,4-dihydroquinol-2-on-1-yl, benzoxazol-2-on-3-yl, quinol-2-on-1-yl, quinol-2-yl or indol-2-yl, each optionally mono substituted with halogen or C.sub.1 -C.sub.4 alkyl on the benzene portion of the respective fused ring moieties.

Sulfonamide anti-arrhythmic agents

A series of novel N-alkyl-N-(alkanesulphonamidoheterocyclicmethyl)-4-alkanesulphonamidophene tyl mines have been prepared, including their pharmaceutically acceptable salts and various key novel intermediates therefor. The heterocyclic moiety present in these compounds is a benzo-fused heterocyclic group derived from either benzofuran, benzothiophene, benzoxazole or quinoline, and it is attached to the adjacent methyl group of the molecule by means of the available ring carbon atom which is situated alpha to the hetero atom. These particular compounds are useful in therapy as highly effective anti-arrhythmic agents and therefore, are of value in the treatment of various cardiac arrhythmias. Preferred member compounds include N-methyl-N-(5-methanesulphonamidobenzofur-2-ylmethyl)-4-methanesulphonamid op henethylamine and N-methyl-N-(6-methanesulphonamidoquinol-2-ylmethyl)-4-methanesulphonamidop hen thylamine. Methods for preparing all these compounds from known starting materials are provided.

A series of novel alkanesulphonamidophenyl-N-alkyl-N-(heterocyclic-alkyl)alkylamine derivatives have been prepared, including their pharmaceutically acceptable salts, wherein the heterocyclic moiety is a 5- or 6-membered nitrogen-containing heterocyclic group which is attached to the adjacent carbon atom by a carbon or nitrogen atom and optionally contains a further heteroatom selected from oxygen and nitrogen, said nitrogen-containing heterocyclic group being either (i) substituted by a phenyl or benzyl group or (ii) fused at two adjacent carbon atoms to a benzene ring, with the resulting heterocyclic ring moiety also being optionally substituted. These particular compounds are useful in therapy as highly effective anti-arrhythmic agents and therefore, are of value in the treatment of various cardiac arrythmias. The most preferred member compound of the series is 2-hydroxy-2-(4-methanesulphonamidophenyl)-N-methyl-N-[2-(6-chloro-2H-isoin dolin-1-on-2-yl)ethyl]ethylamine. Methods for preparing all these compounds from known starting materials are provided.

Isoindolinone sulfonamide anti-arrhythmic agents

Heterocyclic thromboxane synthetase inhibitors of the formula ##STR1## wherein R.sup.1, which is attached to the 2-, 3- or 4-position, is hydrogen, halogen, C.sub.1 -C.sub.4 alkyl, hydroxy or C.sub.1 -C.sub.4 alkoxy;

Heterocyclic thromboxane synthetase inhibitors and pharmaceutical

Novel (2-imidazolin-2-ylamino) substituted quinoxalines and -quinazolines, their preparation and use as antihypertensive agents are described.

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Sandwich, United Kingdom

Geoffrey N Thomas