Discovery and initial SAR of 2-amino-5-carboxamidothiazoles as inhibitors of the Src-family kinase p56(Lck).
A novel series of 2-amino-5-carboxamidothiazoles were identified as inhibitors of Lck. Structure-activity studies demonstrate the structural requirements for potent Lck activity. Cyclopropylamide 11d is a potent Lck inhibitor having sub-micromolar activity in a PBL proliferation assay.
Department of Discovery Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000, USA. jwityak@gnf.org
John
J
Wityak
Jagabandhu
J
Das
Robert V
RV
Moquin
Zhongqi
Z
Shen
James
J
Lin
Ping
P
Chen
Arthur M
AM
Doweyko
Sidney
S
Pitt
Suhong
S
Pang
Ding Ren
DR
Shen
Qiong
Q
Fang
Henry F
HF
de Fex
Gary L
GL
Schieven
Steven B
SB
Kanner
Joel C
JC
Barrish
D000595:Amino Acid Sequence; D001665:Binding Sites; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D013844:Thiazoles; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)