A novel series of highly potent benzimidazole-based microsomal triglyceride transfer protein inhibitors.
Article Details
- CitationCopy to clipboard
Robl JA, Sulsky R, Sun CQ, Simpkins LM, Wang T, Dickson JK Jr, Chen Y, Magnin DR, Taunk P, Slusarchyk WA, Biller SA, Lan SJ, Connolly F, Kunselman LK, Sabrah T, Jamil H, Gordon D, Harrity TW, Wetterau JR
A novel series of highly potent benzimidazole-based microsomal triglyceride transfer protein inhibitors.
J Med Chem. 2001 Mar 15;44(6):851-6.
- PubMed ID
- 11300866 [ View in PubMed]
- Abstract
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.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Lomitapide Microsomal triglyceride transfer protein large subunit IC 50 (nM) 0.8 N/A N/A Details Lomitapide Microsomal triglyceride transfer protein large subunit IC 50 (nM) 8 N/A N/A Details