title: Identification of an N-oxide pyridine GW4064 analog as a potent FXR agonist.
abstract: According to the docking studies and the analysis of a co-crystal structure of GW4064 with FXR, a series of 3-aryl heterocyclic isoxazole analogs were designed and synthesized. N-Oxide pyridine analog (7b) was identified as a promising FXR agonist with potent binding affinity and good efficacy, supporting our hypothesis that through an additional hydrogen bond interaction between the pyridine substituent of isoxazole analogs and Tyr373 and Ser336 of FXR, binding affinity and functional activity could be improved.
authors.affiliation: Roche R&D Center(China) Ltd, 720 Cai Lun Road, Building 5, Pudong, Shanghai 201203, China.
authors.forename: Song
authors.initials: S
authors.lastname: Feng
authors.forename: Minmin
authors.initials: M
authors.lastname: Yang
authors.forename: Zhenshan
authors.initials: Z
authors.lastname: Zhang
authors.forename: Zhanguo
authors.initials: Z
authors.lastname: Wang
authors.forename: Di
authors.initials: D
authors.lastname: Hong
authors.forename: Hans
authors.initials: H
authors.lastname: Richter
authors.forename: Gregory Martin
authors.initials: GM
authors.lastname: Benson
authors.forename: Konrad
authors.initials: K
authors.lastname: Bleicher
authors.forename: Uwe
authors.initials: U
authors.lastname: Grether
authors.forename: Rainer E
authors.initials: RE
authors.lastname: Martin
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Plancher
authors.forename: Bernd
authors.initials: B
authors.lastname: Kuhn
authors.forename: Markus Georg
authors.initials: MG
authors.lastname: Rudolph
authors.forename: Li
authors.initials: L
authors.lastname: Chen