4-substituted-3-substituted-amino-cyclobut-3-ene-1,2-diones and analogs thereof as novel potassium channel openers

A pharmaceutical composition for treating or inhibiting disorders associated with smooth muscle contraction, via potassium channel modulation in warm-blooded animals in need thereof, which comprises administering to said warm-blooded animals, an effective amount of a compound of general Formula (II)

• 38
• wherein:
• R1, R2, and R3, are, independently, hydrogen, halogen, nitro, cyano, alkyl of 1 to 10 carbon atoms (optionally substituted with halogen), cycloalkyl of 3 to 10 carbon atoms, —OR7, amino, alkylamino of 1 to 10 carbon atoms, —SO3H, —SO2N2, —SONH2, —NHSO2R7,
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• —SO2R7, carboxyl, aryl of 6 to 12 carbon atoms or aroyl of 7 to 12 carbon atoms;
• A is a moiety selected from the group consisting of a bond, —CH2—, —CH═CH— and —CHCOR6;
• W is selected from the group consisting of carbon and nitrogen and wherein the carbon atom may be optionally substituted with -R1, -R2 and -R3;
• R4 is alkyl of 1 to 10 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, aralkyl of 7 to 20 carbon atoms wherein the aryl group is optionally substituted with alkyl of 1 to 10 carbon atoms cyano, —OR7,
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• trifluoromethyl or trifluoromethoxy;
• R5 is hydrogen, alkyl of 1 to 10 carbon atoms, formyl, alkanoyl of 2 to 7 carbon atoms, alkenoyl of 3 to 7 carbon atoms,
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• —SO2R7, aroyl of 7 to 12 carbon atoms, arylalkenoyl of 9 to 20 carbon atoms, arylsulfonyl of 6 to 12 carbon atoms, arylalkenoyl of 8 to 12 carbon atoms or arylalkylsulfonyl of 7 to 12 carbon atoms;
• R6 is a chain alkyl of 1 to 10 carbon atoms, or aryl of 6 to 12 carbon atoms;
• R7 is alkyl of 1 to 10 carbon atoms (optionally substituted with halogen);
• aroyl is benzoyl and naphthoyl optionally substituted with one to three substituents each independently selected from the group halogen, cyano, alkyl of 1 to 10 carbon atoms, alkoxy of 1 to 10 Carbon atoms,
• —CF3, and phenyl;
• aryl is naphthyl, phenyl or phenyl optionally substituted with one to three substituents each independently selected from the group halogen, carboxy, alkyl of 1 to 10 carbon atoms, nitro, amino, alkoxy of 1 to 10 carbon atoms, and alkylamino of 1 to 10 carbon atoms;
• or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers or excipients.

A method of treating or inhibiting disorders associated with smooth muscle contraction, via potassium channel modulation in warm-blooded animals in need thereof, which comprises administering to said warm-blooded animals, an effective amount of a compound of general Formula (II);

• 44
• wherein:
• R1, R2, and R3, are, independently, hydrogen, halogen, nitro, cyano, alkyl of 1 to 10 carbon atoms (optionally substituted with halogen) cycloalkyl of 3 to 10 carbon atoms, —OR7, amino, alkylamino of 1 to 10 carbon atoms, —SO3H, —SO2NH2, —SONH2, —NHSO2R7,
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• —SO2R7, carboxyl, aryl of 6 to 12 carbon atoms or aroyl of 7 to 12 carbon atoms;
• A is a moiety selected from the group consisting of a bond, —CH2—, —CH═CH— and —CHCOR6;
• W is selected from the group consisting of carbon and nitrogen and wherein the carbon atom may be optionally substituted with -R1,-R2and -R3;
• R4 is alkyl of 1 to 10 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, aralkyl of 7 to 20 carbon atoms, wherein the aryl group is optionally substituted with alkyl of 1 to 10 carbon atoms, nitro, halogen, cyano, —OR7,
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• trifluoromethyl or trifluoromethoxy;
• R5 is hydrogen, alkyl of 1 to 10 carbon atoms, formyl, alkanoyl of 2 to 7 carbon atoms, alkenoyl of 3 to 7 carbon atoms,
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• —SO2R7, aroyl of 7 to 12 carbon atoms, arylalkenoyl of 9 to 20 carbon atoms, arylsulfonyl of 6 to 12 carbon atoms, arylalkanoyl of 8 to 12 carbon atoms or arylalkylsulfonyl of 7 to 12 carbon atoms;
• R6 is alkyl of 1 to 10 carbon atoms, or aryl of 6 to 12 carbon atoms;
• R7 is alkyl of 1 to 10 carbon atoms (optionally substituted with halogen);
• aroyl is benzoyl and naphthoyl optionally substituted with one to three substituents each independently selected from the group halogen, cyano, alkyl of 1 to 10 carbon atoms, alkoxy of 1 to 10 carbon atoms, —CF3, and phenyl;
• aryl is naphthyl, phenyl or phenyl optionally substituted with one to three substituents each independently selected from the group halogen, carboxy, alkyl of 1 to 10 carbon atoms, nitro, amino, alkoxy of 1 to 10 carbon atoms, and alkylamino of 1 to 10 carbon atoms;
• or a pharmaceutically acceptable salt.