title: Design, synthesis and structure-activity-relationship of 1,5-tetrahydronaphthyridines as CETP inhibitors.
abstract: This Letter describes the discovery and SAR optimization of 1,5-tetrahydronaphthyridines, a new class of potent CETP inhibitors. The effort led to the identification of 21b and 21d with in vitro human plasma CETP inhibitory activity in the nanomolar range (IC(50)=23 and 22nM, respectively). Both 21b and 21d exhibited robust HDL-c increase in hCETP/hApoA1 dual heterozygous mice model.
authors.affiliation: Centro de Investigación Lilly, Avda. de Industria, 30, 28108 Alcobendas, Madrid, Spain. mc.fernandez@lilly.com
authors.forename: Maria-Carmen
authors.initials: MC
authors.lastname: Fernandez
authors.forename: Ana
authors.initials: A
authors.lastname: Escribano
authors.forename: Ana I
authors.initials: AI
authors.lastname: Mateo
authors.forename: Saravanan
authors.initials: S
authors.lastname: Parthasarathy
authors.forename: Eva M
authors.initials: EM
authors.lastname: Martin de la Nava
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wang
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Cockerham
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Beyer
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Schmidt
authors.forename: Guoqing
authors.initials: G
authors.lastname: Cao
authors.forename: Youyan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Jones
authors.forename: Anthony
authors.initials: A
authors.lastname: Borel
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Sweetana
authors.forename: Ellen A
authors.initials: EA
authors.lastname: Cannady
authors.forename: Gregory
authors.initials: G
authors.lastname: Stephenson
authors.forename: Scott
authors.initials: S
authors.lastname: Frank
authors.forename: Nathan B
authors.initials: NB
authors.lastname: Mantlo
mesh_terms: D000818:Animals; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors*; D008076:Cholesterol, HDL; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D009287:Naphthyridines / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D009287:Naphthyridines