title: 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.
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.
authors.affiliation: Pfizer Inc., Groton, CT 06340, USA. jin.li@pfizer.com
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Brian S
authors.initials: BS
authors.lastname: Bronk
authors.forename: John P
authors.initials: JP
authors.lastname: Dirlam
authors.forename: Alan E
authors.initials: AE
authors.lastname: Blize
authors.forename: Peter
authors.initials: P
authors.lastname: Bertinato
authors.forename: Burton H
authors.initials: BH
authors.lastname: Jaynes
authors.forename: Anne
authors.initials: A
authors.lastname: Hickman
authors.forename: Christine
authors.initials: C
authors.lastname: Miskell
authors.forename: Usha A
authors.initials: UA
authors.lastname: Pillai
authors.forename: Jay S
authors.initials: JS
authors.lastname: Tibbitts
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Haven
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Kolosko
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Barry
authors.forename: Tara B
authors.initials: TB
authors.lastname: Manion
mesh_terms: D000818:Animals; D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004285:Dogs; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D008968:Molecular Conformation; D009765:Obesity / Q000188:drug therapy*; D051381:Rats
chemical_list: D002219:Carbamates; D002264:Carboxylic Acids; D002352:Carrier Proteins; D007211:Indoles; C106092:microsomal triglyceride transfer protein; C521290:dirlotapide