Quinuclidine derivatives as squalene synthase inhibitors

Details Quinuclidine derivatives as squalene synthase inhibitors Quinuclidine derivatives as squalene synthase inhibitors

C - Chemistry, Metallurgy

07

D

C07D 453/02 (2006.01) A61K 31/435 (2006.01) A61K 31/495 (2006.01)

Patent

CA 2143430

Compounds of formula (I) and their pharmaceutically acceptable salts in which R1 is hydrogen or hydroxy; R2 is hydrog- en; or R1 and R2 are joined together so that CR1-CR2 is a double bond; X is selected from -CH2CH2-, -CH = CH-, -C ? C-, -CH2O-, -CH2NH-, -NHCH2-, -CH2CO-, -COCH2-, -CH2S- and -SCH2-; Ar1 is a phenylene moiety; Ar2 is a heteroaryl moiety; and wherein one or both of Ar1 and Ar2 may optionally bear one or more substituents independently selected from halogeno, hydroxy, amino, nitro, cyano, carboxy, carbamoyl, alkyl, alkenyl, alkynyl, alkoxy, alkylamino, di-alkylamino, N- alkylcarbamoyl, di-N,N-alkylcarbamoyl, alkoxycarbonyl, alkylthio, alkylsulphinyl, alkylsulphonyl, halogeno-alkyl, carbox- yalkyl and alkanoylamino; provided that when R1 is hydroxy, X is not selected from -NHCH2- and -SCH2-; are inhibitors of squalene synthase and hence useful in treating medical conditions in which a lowering of cholesterol is beneficial, such as hypercholesterolemia and atherosclerosis. Processes for preparing these derivatives, pharmaceutical compositions contain- ing them are also described together with their use in medicine.

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