Discovery of 2-amino-heteroaryl-benzothiazole-6-anilides as potent p56(lck) inhibitors.
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.
Das
Jagabandhu
J
Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA. jagabandhu.das@bms.com
Moquin
Robert V
RV
Lin
James
J
Liu
Chunjian
C
Doweyko
Arthur M
AM
DeFex
Henry F
HF
Fang
Qiong
Q
Pang
Suhong
S
Pitt
Sidney
S
Shen
Ding Ren
DR
Schieven
Gary L
GL
Barrish
Joel C
JC
Wityak
John
J
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*
D000813:Anilides; D004791:Enzyme Inhibitors; D013844:Thiazoles; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)