title: Discovery of 2-amino-heteroaryl-benzothiazole-6-anilides as potent p56(lck) inhibitors.
abstract: A series of structurally novel benzothiazole based small molecule inhibitors of p56(lck) was prepared to elucidate their structure-activity relationships (SAR), selectivity and cell activity in the T-cell proliferation assay. BMS-350751 (2) and BMS-358233 (3) are identified as potent Lck inhibitors with excellent cellular activities against T-cell proliferation.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA. jagabandhu.das@bms.com
authors.forename: Jagabandhu
authors.initials: J
authors.lastname: Das
authors.forename: Robert V
authors.initials: RV
authors.lastname: Moquin
authors.forename: James
authors.initials: J
authors.lastname: Lin
authors.forename: Chunjian
authors.initials: C
authors.lastname: Liu
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
authors.forename: John
authors.initials: J
authors.lastname: Wityak
mesh_terms: D000813:Anilides / Q000138:chemical synthesis* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000813:Anilides; D004791:Enzyme Inhibitors; D013844:Thiazoles; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)