In vitro and in vivo profile of 5-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-1H-indole-2-carboxylic acid benzylmethyl carbamoylamide (dirlotapide), a novel potent MTP inhibitor for obesity

  • Bioorg Med Chem Lett. 2007 Apr 1;17(7):1996-9. doi: 10.1016/j.bmcl.2007.01.018.
Jin Li  1 ,  Brian S Bronk ,  John P Dirlam ,  Alan E Blize ,  Peter Bertinato ,  Burton H Jaynes ,  Anne Hickman ,  Christine Miskell ,  Usha A Pillai ,  Jay S Tibbitts ,  Michelle L Haven ,  Nicole L Kolosko ,  Chris J Barry ,  Tara B Manion
Affiliations
PMID: 17276061 DOI: 10.1016/j.bmcl.2007.01.018
Abstract

The synthesis of a novel gut selective MTP inhibitor, 5-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-1H-indole-2-carboxylic acid benzylmethyl carbamoylamide (dirlotapide), and its in vitro and in vivo profile are described. Dirlotapide (3) demonstrated excellent potency against MTP enzyme in HepG2 cells and canine hepatocytes. This novel MTP inhibitor also showed excellent efficacy when tested in a canine food intake model.