194214-90-9Relevant academic research and scientific papers
A novel series of highly potent benzimidazole-based microsomal triglyceride transfer protein inhibitors
Robl,Sulsky,Sun,Simpkins,Wang,Dickson Jr.,Chen,Magnin,Taunk,Slusarchyk,Biller,Lan,Connolly,Kunselman,Sabrah,Jamil,Gordon,Harrity,Wetterau
, p. 851 - 856 (2001)
A series of benzimidazole-based analogues of the potent MTP inhibitor BMS-201038 were discovered. Incorporation of an unsubstituted benzimidazole moiety in place of a piperidine group afforded potent inhibitors of MTP in vitro which were weakly active in vivo. Appropriate substitution on the benzimidazole ring, especially with small alkyl groups, led to dramatic increases in potency, both in a cellular assay of apoB secretion and especially in animal models of cholesterol lowering. The most potent in this series, 3g (BMS-212122), was significantly more potent than BMS-201038 in reducing plasma lipids (cholesterol, VLDL/LDL, TG) in both hamsters and cynomolgus monkeys.
Conformationally restricted aromatic inhibitors of microsomal triglyceride transfer protein and method
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, (2008/06/13)
Novel compounds are provided which are inhibitors of MTP and thus are useful for lowering serum lipids and treating atherosclerosis and related diseases, and have the structure STR1 including pharmaceutically acceptable salts thereof or prodrug esters thereof, wherein q is 0, 1 or 2; Rx is H, alkyl, aryl or halogen; A is (1) a bond; (2) --O--; or (3) STR2 B is: STR3 and wherein L2, L1, R1, R2, R3, R3', R3a, R3b, R4, R4', R5, X, STR4 are as defined herein.
