title: 2-Aminopyrimidin-4(1H)-one as the novel bioisostere of urea: discovery of novel and potent CXCR2 antagonists.
abstract: 2-Aminopyrimidin-4(1H)-one was proposed as the novel bioisostere of urea. Bioisosteric replacement of the reported urea series of the CXCR2 antagonists with 2-aminopyrimidin-4(1H)-ones led to the discovery of the novel and potent CXCR2 antagonist 3e. 2-Aminopyrimidin-4(1H)-one derivative 3e demonstrated a good developability profile (reasonable solubility and high permeability) and superior chemical stability especially in simulated gastric fluid (SGF) compared with ureas.
authors.affiliation: Research and Development, GlaxoSmithKline, 898 Halei Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai 201203, PR China.
authors.forename: Hongfu
authors.initials: H
authors.lastname: Lu
authors.affiliation: Research and Development, GlaxoSmithKline, 898 Halei Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai 201203, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
authors.affiliation: Research and Development, GlaxoSmithKline, 898 Halei Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai 201203, PR China.
authors.forename: Zhongmiao
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Research and Development, GlaxoSmithKline, 898 Halei Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai 201203, PR China.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Wren
authors.affiliation: Research and Development, GlaxoSmithKline, 898 Halei Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai 201203, PR China.
authors.forename: Yueting
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Research and Development, GlaxoSmithKline, 898 Halei Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai 201203, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Cai
authors.affiliation: GlaxoSmithKline, Platform Technology & Science, Biological Sciences, Gunnels Wood Road, Stevenage, Herts SG1 2NY, UK.
authors.forename: Metul
authors.initials: M
authors.lastname: Patel
authors.affiliation: Research and Development, GlaxoSmithKline, 898 Halei Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai 201203, PR China.
authors.forename: Kelly
authors.initials: K
authors.lastname: Dong
authors.affiliation: Research and Development, GlaxoSmithKline, 898 Halei Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai 201203, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Research and Development, GlaxoSmithKline, 898 Halei Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai 201203, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Research and Development, GlaxoSmithKline, 898 Halei Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai 201203, PR China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Guan
authors.affiliation: Research and Development, GlaxoSmithKline, 898 Halei Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai 201203, PR China.
authors.forename: Jianing
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Research and Development, GlaxoSmithKline, 898 Halei Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai 201203, PR China.
authors.forename: John D
authors.initials: JD
authors.lastname: Elliott
authors.affiliation: Research and Development, GlaxoSmithKline, 898 Halei Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai 201203, PR China.
authors.forename: Xichen
authors.initials: X
authors.lastname: Lin
authors.affiliation: Research and Development, GlaxoSmithKline, 898 Halei Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai 201203, PR China. Electronic address: feng.q.ren@gsk.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Ren
mesh_terms: D006801:Humans; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives*
chemical_list: D011743:Pyrimidines; D023063:Receptors, Interleukin-8B; D014508:Urea
keywords: 2-Aminopyrimidin-4(1H)-one; Bioisostere; CXCR2 antagonists; Urea