.alpha.-phosphonocarboxylate squalene synthetase inhibitors

Details .alpha.-phosphonocarboxylate squalene synthetase inhibitors .alpha.-phosphonocarboxylate squalene synthetase inhibitors

C - Chemistry, Metallurgy

07

F

C07F 9/38 (2006.01) A61K 31/66 (2006.01) C07F 9/40 (2006.01) C07F 9/547 (2006.01)

Patent

CA 2109771

Abstract .alpha.-PHOSPHONOCARBOXLATE SQUALENE SYNTHETASE INHIBITORS AND METHOD .alpha.-Phosphonocarboxylate compounds are provided which inhibit the enzyme squalene synthetase and thereby inhibit cholesterol biosynthesis. These compounds have the formula Image wherein R1 is a lipophilic group which contains at least 7 carbons and is substituted alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted arylalkyl or optionally substituted aryl; Z is H, halogen, hydroxy, hydroxyalkyl or lower alkyl; R2 and R3 are independently H, metal ion or other pharmaceutically acceptable cation, or a prodrug ester; R4 is H, metal ion or other pharmaceutically acceptable cation lower alkyl, lower alkenyl, arylalkyl, aryl or a prodrug ester.

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