title: Discovery of thiadiazole amides as potent, S1P₃-sparing agonists of sphingosine-1-phosphate 1 (S1P₁) receptor.
abstract: High-throughput screening of GSK compound collection led to the discovery of a novel series of thiadiazole amides as potent and S1P(3)-sparing sphingosine-1-phosphate 1 (S1P(1)) receptor agonists. Synthesis, structure and activity relationship, selectivity, and some developability properties are described.
authors.affiliation: GlaxoSmithKline Pharmaceuticals, R&D China, 898 Halei Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai 201023, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Xu
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhang
authors.forename: Linbo
authors.initials: L
authors.lastname: Luan
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Chengyong
authors.initials: C
authors.lastname: Li
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Wang
authors.forename: Fangbin
authors.initials: F
authors.lastname: Han
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
authors.forename: Feng
authors.initials: F
authors.lastname: Ren
authors.forename: Jia-Ning
authors.initials: JN
authors.lastname: Xiang
authors.forename: John D
authors.initials: JD
authors.lastname: Elliott
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Taylor B
authors.initials: TB
authors.lastname: Guo
authors.forename: Hongtao
authors.initials: H
authors.lastname: Lu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: David
authors.initials: D
authors.lastname: Hirst
authors.forename: Matthew
authors.initials: M
authors.lastname: Lindon
authors.forename: Xichen
authors.initials: X
authors.lastname: Lin
mesh_terms: D000577:Amides / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D055808:Drug Discovery; D057166:High-Throughput Screening Assays; D006801:Humans; D007155:Immunologic Factors / Q000737:chemistry* / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D051379:Mice; D049349:Receptors, Lysosphingolipid / Q000819:agonists* / Q000737:chemistry; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000577:Amides; D007155:Immunologic Factors; D049349:Receptors, Lysosphingolipid; D054852:Small Molecule Libraries; D013830:Thiadiazoles