title: Design, synthesis, and biological evaluation of (2R,alphaS)-3,4-dihydro-2-[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-5-[3-(trifluoromethoxy)-phenyl]-alpha-(trifluoromethyl)-1(2H)-quinolineethanol as potent and orally active cholesteryl ester transfer protein inhibitor.
abstract: With the goal of identifying a CETP inhibitor with high in vitro potency and optimal in vivo efficacy, a conformationally constrained molecule was designed based on the highly potent and flexible 13. The synthetic chemistry efforts led to the discovery of the potent and selective 12. In high-fat fed hamsters, human CETP transgenic mice, and cynomolgus monkeys, the in vivo efficacy of 12 for raising HDL-C was demonstrated to be comparable to torcetrapib.
authors.affiliation: Drug Discovery Division, Johnson and Johnson Pharmaceutical Research and Development, LLC 8 Clarke Drive, Cranbury, New Jersey 08512, USA. gkuo@its.jnj.com
authors.forename: Gee-Hong
authors.initials: GH
authors.lastname: Kuo
authors.forename: Thomas
authors.initials: T
authors.lastname: Rano
authors.forename: Patricia
authors.initials: P
authors.lastname: Pelton
authors.forename: Keith T
authors.initials: KT
authors.lastname: Demarest
authors.forename: Alan C
authors.initials: AC
authors.lastname: Gibbs
authors.forename: William V
authors.initials: WV
authors.lastname: Murray
authors.forename: Bruce P
authors.initials: BP
authors.lastname: Damiano
authors.forename: Margery A
authors.initials: MA
authors.lastname: Connelly
mesh_terms: D000284:Administration, Oral; D000818:Animals; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors*; D006224:Cricetinae; D004041:Dietary Fats / Q000008:administration & dosage; D015195:Drug Design; D006801:Humans; D008252:Macaca fascicularis; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: C539971:3,4-dihydro-2-(3-(1,1,2,2-tetrafluoroethoxy)phenyl)-5-(3-(trifluoromethoxy)phenyl)-alpha-(trifluoromethyl)-1(2H)-quinolineethanol; D053480:Cholesterol Ester Transfer Proteins; D004041:Dietary Fats; D011804:Quinolines