.alpha.-phosphonosulfonate squalene synthetase inhibitors

Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...

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514 94, 514114, 514127, 514 79, 514 80, 514 81, 514 86, 514 89, 514 92, 544232, 544243, 544244, 546 23, 540450, 540471, 540474, 540542, 548112, 548113, 558 45, 562 17, 562 21, 562 23, 562 35, C07F 938, C07F 9553, C07F 96506, C07F 96512, A61K 3166

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active

057123969

ABSTRACT:
.alpha.-Phosphonosulfonate compounds are provided which inhibit the enzyme squalene synthetase and thereby inhibit cholesterol biosynthesis. These compounds have the formula ##STR1## wherein R.sup.2 is OR.sup.5 or R.sup.5a ; R.sup.3 and R.sup.5 are independently H, alkyl, arylalkyl, aryl or cycloalkyl; R.sup.5a is H, alkyl, arylalkyl or aryl; R4 is H, alkyl, aryl, arylalkyl, or cycloalkyl;, Z is H, halogen, lower alkyl or lower alkenyl; and R.sup.1 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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