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.
Wityak
John
J
Department of Discovery Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000, USA. jwityak@gnf.org
Das
Jagabandhu
J
Moquin
Robert V
RV
Shen
Zhongqi
Z
Lin
James
J
Chen
Ping
P
Doweyko
Arthur M
AM
Pitt
Sidney
S
Pang
Suhong
S
Shen
Ding Ren
DR
Fang
Qiong
Q
de Fex
Henry F
HF
Schieven
Gary L
GL
Kanner
Steven B
SB
Barrish
Joel C
JC
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)