title: Molecular design, synthesis, and structure-Activity relationships leading to the potent and selective p56(lck) inhibitor BMS-243117.
abstract: A series of structurally novel benzothiazole based small molecule inhibitors of p56(lck) were prepared to elucidate their structure-activity relationships (SARs), selectivity and cell activity in the T-cell proliferation assay. BMS-243117 (compound 2) is identified as a potent, and selective Lck inhibitor with good cellular activity (IC(50)=1.1 microM) against T-cell proliferation.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, 08543-4000, Princeton, NJ, USA. jagabandhu.das@bms.com
authors.forename: Jagabandhu
authors.initials: J
authors.lastname: Das
authors.forename: James
authors.initials: J
authors.lastname: Lin
authors.forename: Robert V
authors.initials: RV
authors.lastname: Moquin
authors.forename: Zhongqi
authors.initials: Z
authors.lastname: Shen
authors.forename: Steven H
authors.initials: SH
authors.lastname: Spergel
authors.forename: John
authors.initials: J
authors.lastname: Wityak
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Doweyko
authors.forename: Henry F
authors.initials: HF
authors.lastname: DeFex
authors.forename: Qiong
authors.initials: Q
authors.lastname: Fang
authors.forename: Suhong
authors.initials: S
authors.lastname: Pang
authors.forename: Sidney
authors.initials: S
authors.lastname: Pitt
authors.forename: Ding Ren
authors.initials: DR
authors.lastname: Shen
authors.forename: Gary L
authors.initials: GL
authors.lastname: Schieven
authors.forename: Joel C
authors.initials: JC
authors.lastname: Barrish
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001665:Binding Sites / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013601:T-Lymphocytes / Q000187:drug effects; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D014508:Urea / Q000737:chemistry
chemical_list: C481959:BMS-243117; D004791:Enzyme Inhibitors; D013844:Thiazoles; D000255:Adenosine Triphosphate; D014508:Urea; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)