Antiarrhythmic imidazoliums, intermediates thereto and...

C - Chemistry – Metallurgy – 07 – D

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167/231, 167/233

C07D 233/56 (2006.01) A61K 31/415 (2006.01) C07C 17/00 (2006.01) C07C 17/26 (2006.01) C07C 17/263 (2006.01) C07C 33/48 (2006.01) C07C 33/50 (2006.01) C07C 45/65 (2006.01) C07D 401/02 (2006.01) C07D 405/02 (2006.01) C07D 521/00 (2006.01)

Patent

CA 1289563

ABSTRACT OF THE DISCLOSURE Imidazolium salts described are useful as antiarrhythmic agents. A method of treating arrhythmia by increasing the refractoriness of cardiac tissue is provided as well as pharmaceutical formulations containing such imidazolium salts. The invention thus provides compounds having the formula as a compound of the formula: Image wherein R = straight or branched chain alkyl having 1-12 carbon atoms, C5-C6 cycloalkyl (lower)alkyl, Image , or Image ; R1,R2,R3 = hydrogen, a straight chain alkyl group of 1-4 carbon atoms R4,R5 = hydrogen, halogen, hydroxy, lower alkyl, lower alkoxy, cyano, nitro, carbamoyl, lower alkylcarbamoyl, lower alkanoylamido, sulfamoyl, sulfamoyl substituted by a straight or branched 1-4 carbon chain on the sulfamoyl nitrogen, which in turn may be substituted by a phenyl or C1-C4-alkoxy group, sulfamoylamino, N-lower alkylsulfamoylamino, lower alkylsulfonamido, lower alkylsulfonamido substituted by phenyl or C1-C4-alkoxy group on the lower alkyl moiety, trifluoromethanesulfonamido, ureido, N-lower alkylureido or when taken together on adjacent carbon atoms of the ring to which they are attached may be joined to form the methylene dioxy moiety; R6 = hydrogen, halogen, hydroxy, straight chain alkyl of 1-6 carbon atoms, lower alkoxy, cyano and carbamoyl; A = phenyl, furanyl, pyridinyl, pyrrolyl, thiazoly, oxazolyl, the benzo derivatives of the foregoing and thiadiazolyl; n = 0-2, p = 0-5. t = 1-5, Y = methylene, hydroxymethylene, arylmethylene represented by the formula. Image Image Image , or Image phenylene, ethynylene, Image , Image , carbonyl, ?B-R11, -NHSO2-, -SO2NH- wherein R7, R8 is hydrogen, C1-C4 lower alkyl or taken together form a 5 or 6 membered ring selected from Image , Image , Image , Image , Image or Image R9, R10 is C1-C4 lower alkyl, or taken together with -CH1-CH1 may form a 5 or 6 membered ring R11 is hydrogen, lower alkyl, cyano and carbamoyl, with the provisos that (a) when Y is ? N-R11, -SO2NH-, -NHSO2-, then p must be an integer of 2-5, (b) when Y is a hydroxymethylene then R cannot be Image

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