Alpha-phosphorus substituted sulfinate derivatives as squalene synthetase inhibitors

摘要

α-Phosphonosulfinate compounds are provided which inhibit the enzyme squalene synthetase and thereby inhibit cholesterol biosynthesis. These compounds have the formula
<Chemistry id="chema01" num="0001"><Image id="ia01" he="20" wi="42" file="IMGA0001.TIF" imgContent="chem" imgFormat="TIFF" /></Chemistry>
wherein R² is OR⁵ or R<Sup>5a</Sup>; R³ and R⁵ are independently H, alkyl, arylalkyl, aryl or cycloalkyl; R<Sup>5a</Sup> is alkyl, arylalkyl or aryl; R⁴ is H or pharmaceutically acceptable cation;, 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;
including pharmaceutically acceptable salts.