Albright J D, DeVries V G, Du M T, Largis E E, Miner T G, Reich M F, Shepherd R G
J Med Chem. 1983 Oct;26(10):1393-411. doi: 10.1021/jm00364a010.
The synthesis of a series of analogues in which the carboxylic acid group of cetaben is replaced by carboxylate ester, carboxamide, or a variety of other substituent groups is described. Also reported are the syntheses of analogues in which the phenyl ring of cetaben is either modified by the presence of additional substituents or replaced entirely by another moiety. Structure-activity relationships of these compounds both as hypolipidemic agents and as inhibitors of the enzyme fatty acyl-CoA:cholesterol acyltransferase (ACAT) are discussed. Analogue syntheses designed to produce compounds that would be better absorbed orally than cetaben failed to yield any congeners of enhanced biological activity. In contrast, analogue syntheses directed toward non carboxylic acids of similar acidity to cetaben produced a very active class of sulfonamides.
描述了一系列类似物的合成，其中西他苯的羧酸基团被羧酸酯、羧酰胺或各种其他取代基取代。还报道了西他苯的苯环被其他取代基修饰或完全被另一个部分取代的类似物的合成。讨论了这些化合物作为降血脂剂和脂肪酸酰基辅酶A：胆固醇酰基转移酶（ACAT）抑制剂的构效关系。旨在生产比西他苯更易口服吸收的化合物的类似物合成未能产生任何具有增强生物活性的同系物。相比之下，针对与西他苯酸度相似的非羧酸的类似物合成产生了一类非常活跃的磺酰胺。
