.alpha.-phosphonosulfonae squalene synthetase inhibitors and...

Details .alpha.-phosphonosulfonae squalene synthetase inhibitors and... .alpha.-phosphonosulfonae squalene synthetase inhibitors and...

C - Chemistry, Metallurgy

07

F

C07F 9/38 (2006.01) A61K 31/66 (2006.01) C07F 9/30 (2006.01) C07F 9/40 (2006.01) C07F 9/48 (2006.01) C07F 9/547 (2006.01) C07F 9/58 (2006.01) C07F 9/59 (2006.01) C07F 9/653 (2006.01) C07F 9/655 (2006.01) C07F 9/6553 (2006.01) C07F 9/6584 (2006.01)

Patent

CA 2107644

Abstract .alpha.-PHOSPHONOSULFONATE SQUALENE SYNTHETASE INHIBITORS AND METHOD .alpha.-Phosphonosulfonate compounds are provided which inhibit the enzyme squalene synthetase and thereby inhibit cholesterol biosynthesis. These comounds have the formula Image wherein R2 is OR5 or R5a; R3 and R5 are independently H, alkyl, arylalkyl, aryl or cycloalkyl; R5a is H, alkyl, arylalkyl or aryl; R4 is H, alkyl, aryl, arylalkyl, or cycloalkyl;, Z is H, halogen, lower alkyl or lower alkenyl; and R1 is a lipophilic group which contains at least 7 carbons and is alkyl, alkenyl, alkynyl, mixed alkenyl-alkynyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, cycloheteroalkyl, cycloheteroalkylalkyl; as further defined above; including pharmaceutically acceptable salts and or prodrug esters of the phosphonic (phosphinic) and/or sulfonic acids.

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