title: 2-(4-carbonylphenyl)benzoxazole inhibitors of CETP: scaffold design and advancement in HDLc-raising efficacy.
abstract: The development of 2-phenylbenzoxazoles as inhibitors of cholesteryl ester transfer protein (CETP) is described. Initial efforts aimed at engineering replacements for the aniline substructures in the benchmark molecule. Reversing the connectivity of the central aniline lead to a new class of 2-(4-carbonylphenyl)benzoxazoles. Structure-activity studies at the C-7 and terminal pyridine ring allowed for the optimization of potency and HDLc-raising efficacy in this new class of inhibitors. These efforts lead to the discovery of benzoxazole 11v, which raised HDLc by 24 mg/dl in our transgenic mouse PD model.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. ramzi.sweis@merck.com
authors.forename: Ramzi F
authors.initials: RF
authors.lastname: Sweis
authors.forename: Julianne A
authors.initials: JA
authors.lastname: Hunt
authors.forename: Florida
authors.initials: F
authors.lastname: Kallashi
authors.forename: Milton L
authors.initials: ML
authors.lastname: Hammond
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Suzanne S
authors.initials: SS
authors.lastname: Eveland
authors.forename: Qiu
authors.initials: Q
authors.lastname: Guo
authors.forename: Sheryl A
authors.initials: SA
authors.lastname: Hyland
authors.forename: Denise P
authors.initials: DP
authors.lastname: Milot
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Cumiskey
authors.forename: Melanie
authors.initials: M
authors.lastname: Latham
authors.forename: Raymond
authors.initials: R
authors.lastname: Rosa
authors.forename: Larry
authors.initials: L
authors.lastname: Peterson
authors.forename: Carl P
authors.initials: CP
authors.lastname: Sparrow
authors.forename: Samuel D
authors.initials: SD
authors.lastname: Wright
authors.forename: Matt S
authors.initials: MS
authors.lastname: Anderson
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sinclair
mesh_terms: D000818:Animals; D001583:Benzoxazoles / Q000737:chemistry* / Q000494:pharmacology*; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors*; D008076:Cholesterol, HDL / Q000097:blood*; D015195:Drug Design; D051379:Mice; D008822:Mice, Transgenic; D013329:Structure-Activity Relationship
chemical_list: D001583:Benzoxazoles; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL