title: SAR studies on the central phenyl ring of substituted biphenyl oxazolidinone-potent CETP inhibitors.
abstract: SAR studies of the substitution effect on the central phenyl ring of the biphenyl scaffold were carried out using anacetrapib (9a) as the benchmark. The results revealed that the new analogs with substitutions to replace trifluoromethyl (9a) had a significant impact on CETP inhibition in vitro. In fact, analogs with some small groups were as potent or more potent than the CF(3) derivative for CETP inhibition. Five of these new analogs raised HDL-C significantly (>20mg/dL). None of them however was better than anacetrapib in vivo. The synthesis and biological evaluation of these CETP inhibitors are described.
authors.affiliation: Department of Medicinal Chemistry, Merck Sharp & Dohme Corp., PO Box 2000, Rahway, NJ 07065, USA. zhijian_lu@merck.com
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Lu
authors.forename: Yi-Heng
authors.initials: YH
authors.lastname: Chen
authors.forename: Joann B
authors.initials: JB
authors.lastname: Napolitano
authors.forename: Gayle
authors.initials: G
authors.lastname: Taylor
authors.forename: Amjad
authors.initials: A
authors.lastname: Ali
authors.forename: Milton L
authors.initials: ML
authors.lastname: Hammond
authors.forename: Qiaolin
authors.initials: Q
authors.lastname: Deng
authors.forename: Eugene
authors.initials: E
authors.lastname: Tan
authors.forename: Xinchun
authors.initials: X
authors.lastname: Tong
authors.forename: Suoyu S
authors.initials: SS
authors.lastname: Xu
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Latham
authors.forename: Laurence B
authors.initials: LB
authors.lastname: Peterson
authors.forename: Matt S
authors.initials: MS
authors.lastname: Anderson
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: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Carl P
authors.initials: CP
authors.lastname: Sparrow
authors.forename: Samuel D
authors.initials: SD
authors.lastname: Wright
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sinclair
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors*; D008076:Cholesterol, HDL / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008822:Mice, Transgenic; D008956:Models, Chemical; D023303:Oxazolidinones / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D023303:Oxazolidinones; C530884:anacetrapib