American Home Products Corporation

Wyeth

David R Herbst

John Anthony Butera

Geraldine Ruth McFarlane

Russell F Graceffa

Dominick Anthony Quagliato

Madelene M Antane

Eric Gould Gundersen

Bradford H Hirth

Eugene John Trybulski

Gregory Scott Welmaker

Joan E Sabalski

Matthew A Wilson

Herchel Smith

The present invention is directed to compounds of Formula I: that are potassium channel modulators and pharmaceutical compositions thereof. The present invention is further directed to methods of treatment using the compounds and pharmaceutical compositions of the invention. The present invention is still further directed to synthetic processes for producing the compounds of the invention.

Benzofurans as potassium ion channel modulators

The compounds of the formula: ##STR1## wherein R.sub.1 and R.sub.2 are, independently, hydrogen, straight chain alkyl, branched chain alkyl, cycloalkyl, bicycloalkyl or aralkyl, wherein the aromatic moiety of the aralkyl group may be optionally substituted with one to three straight chain alkyl, halogen, nitro, cyano, alkoxy, alkoxycarbonyl, trifluoromethyl or trifluoromethoxy groups; R.sub.3 is hydrogen, formyl, alkanoyl, alkenoyl, alkylsulfonyl, aroyl, arylalkenoyl, arylsulfonyl, arylalkanoyl or arylalkylsulfonyl; A is selected from the group consisting of: ##STR2## wherein n is 0 or 1; R.sub.4, R.sub.5 and R.sub.6 are, independently, cyano, nitro, amino, alkyl, perfluoroalkyl, alkoxy, perfluoroalkoxy, alkylamino, dialkylamino, sulfamyl, alkylsulfonamido, arylsulfonamido, alkylcarboxamido, arylcarboxamido, alkanoyl, alkylsulfonyl, perfluoroalkylsulfonyl, arylsulfonyl, chloro, bromo, fluoro, iodo, 1-imidazolyl, carboxyl or hydrogen; or a pharmaceutically acceptable salt thereof, relax smooth muscles.

Heterocyclymethylamino derivatives of cyclobutene-3,4-diones

The compounds of the formula: ##STR1## wherein R.sub.1 is straight chain alkyl, branched chain alkyl, cycloalkyl, hydroxyalkyl, fluoroalkyl or polyfluoroalkyl; R.sub.7 and R.sub.8 are, independently, hydrogen or an acyl substituent selected from the group consisting of formyl, alkanoyl, alkenoyl, alkoxycarbonyl, alkylsulfonyl, aroyl, arylalkenoyl, arylsulfonyl, arylalkanoyl or arylalkylsulfonyl; A is a phenyl group with either two or three substituents of the following formula: ##STR2## wherein the positions of substitution are R.sub.2,R.sub.3 -, R.sub.2,R.sub.4 -, R.sub.2,R.sub.5 -, R.sub.2,R.sub.6 -, R.sub.3,R.sub.4 -, R.sub.3,R.sub.5 -, and R.sub.2,R.sub.4,R.sub.6 - and R.sub.2 is methyl, ethyl, fluoro, chloro, methoxy or trifluoromethyl; R.sub.3 is methyl, ethyl, fluoro, chloro, methoxy or trifluoromethyl; R.sub.4 is methyl, fluoro, bromo, methoxy or cyano; R.sub.5 is methyl, fluoro, chloro, methoxy, cyano or trifluoromethyl; R.sub.6 is methyl, fluoro, chloro, or methoxy; or a pharmaceutically acceptable salt thereof, relax smooth muscles.

Substituted N-arylmethylamino derivatives of cyclobutene-3, 4-diones

The compounds of the formula: ##STR1## wherein R.sub.1 is straight chain alkyl, branched chain alkyl cycloalkyl, hydroxyalkyl, fluoroalkyl or polyfluoroalkyl; R.sub.2 and R.sub.3 are, independently, hydrogen or an acyl substituent selected from the group consisting of formyl, alkanoyl, alkenoyl, alkoxycarbonyl, alkylsulfonyl, aroyl, arylalkenoyl, arylsulfonyl, arylalkanoyl or arylalkylsulfonyl; A is a substituted phenyl group of the following formula: ##STR2## wherein R.sub.4 and R.sub.5 are, independently, cyano, nitro, amino, alkyl, perfluoroalkyl, fluoroalkyl, alkoxy, perfluoroalkoxy, fluoroalkoxy, amino, alkylamino, dialkylamino, sulfamyl, alkylsulfonamido, arylsulfonamido, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, alkylcarboxamido, arylcarboxamido, alkylsulfonyl, perfluoroalkylsulfonyl, arylsulfonyl, chloro, bromo, fluoro, iodo, 1-imidazolyl, carboxyl or hydrogen, with the proviso that R.sub.4 and R.sub.5 cannot both be hydrogen; or a pharmaceutically acceptable salt thereof, relaxes smooth muscles.

Substituted N-arylmethylamino derivatives of cyclobutene-3,4-diones

Substituted 1,2,4,5,6,7,8,9-octahydro-3H-azecino[5,4-b]-indoles and substituted 1,2,3,4,5,6,7,8-octahydroazonino[5,4-b]-indoles are prepared by cleavage of the corresponding quaternary alkyl iodide salts with lithium in liquid ammonia. The products possess diuretic activity.

Indole fused heterocyclic diuretic compounds

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Wayne, PA, United States of America

David R Herbst