“…For purposes of defining minimum structural requirements for maximum antilipemic action of compounds related to clofibrate (ethyl 2-methyl-2- [4-chlorophenoxy] propionate [I]), probing the nature of biochemical sites that are either blocked or stimulated by this hypolipemic drug, classifying such sites according to their selective affinity or intrinsic activity towards analogs resulting from minor molecular modification of I, providing insight into the mechanism(s) of action of such analogs and developing new leads for the design of hypolipemic drugs that have potential use in the treatment of atherosclerosis (1), Witiak and coworkers (2)(3)(4)(5) synthesized for such biological investigations (2-9) a series of acyclic and cyclic analogs Ill-VIII. Preliminary investigations in vitro employing the hydrolysis product of I, namely II, which is presumed to be the active hypolipemic agent in vivo due to rapid metabolism by tissue and serum esterases (10), showed II to have properties similar to those observed for the free acid hydrolysis products of ethyl D,L-2-(4-chlorophenoxy)propionate (III), a simple desmethyl analog of I; ethyl 1,4-benzodioxane-2-carboxylate (IV), an analog derived by bonding the a-methyl group of deschloro III via an ether linkage to the ortho position of the phenyl ring; ethyl 5-chloro-2,3-dihydro-2-benzofurancarboxylate (V) and 2,3-dihydro-2-benzofurancarboxylate (VI), analogs derived by bonding the a-methyl group of III or deschloro-III, respectively, directly to the ortho position of the phenyl ring; and ethyl 6-chlorochroman-2-carboxylate (VII) and ethyl chroman-2-car-boxylate (VIII), derived by bonding the amethyl group of III or deschloro-III, respecttively, via a methylene group to the ortho position of the phenyl ring ( Fig.…”