.alpha.-phosphonosulfonate squalene synthetase inhibitors and method

US5567841A · kind A · utility

Assignee

• Bristol-Myers Squibb Company · US

Inventors

• David R. Magnin · Hillsborough Township, US
• Scott A. Biller · Hopewell, US
• John K. Dickson · Mount Holly, US
• R. Michael Lawrence · Yardley, US
• Richard B. Sulsky · Somerville, US

Key dates

• Filing date: Jun 5, 1995
• Grant date: Oct 22, 1996
• Expiry date: Jun 5, 2015

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07F9/655345
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

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; R.sup.4 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.