gem-Diphosphonate and gem-phosphonate-phosphate compounds with specific high density lipoprotein inducing activity

Abstract
New diphosphonate compounds and related derivatives1 were synthesized and investigated for their activity in specifically inducing plasma high density lipoproteins (HDL) and high density lipoprotein cholesterol (HDL-C) in normal rats. The screening of numerous compounds has permitted the determination of the structural variations leading to optimal plasma lipid altering activity, indicating antiatherosclerotic potential. Among the compounds observed to be the most active, dimethyl .alpha.-(dimethoxyphosphinyl)-p-chlorobenzyl phosphate, (20, SR-202, mifobate) was selected for further pharmacological and subsequent clinical development.