Discovery of novel 2-(aminoheteroaryl)-thiazole-5-carboxamides as potent and orally active Src-family kinase p56(Lck) inhibitors.
A series of substituted 2-(aminoheteroaryl)-thiazole-5-carboxamide analogs have been synthesized as novel, potent inhibitors of the Src-family kinase p56Lck. Among them, compound 2 displayed superior in vitro potency and excellent in vivo efficacy.
Chen
Ping
P
Department of Discovery Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000, USA. ping.chen@bms.com
Norris
Derek
D
Das
Jagabandhu
J
Spergel
Steven H
SH
Wityak
John
J
Leith
Leslie
L
Zhao
Rulin
R
Chen
Bang-Chi
BC
Pitt
Sidney
S
Pang
Suhong
S
Shen
Ding Ren
DR
Zhang
Rosemary
R
De Fex
Henry F
HF
Doweyko
Arthur M
AM
McIntyre
Kim W
KW
Shuster
David J
DJ
Behnia
Kamelia
K
Schieven
Gary L
GL
Barrish
Joel C
JC
D000284:Administration, Oral; D000577:Amides / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000628:therapy; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000037:antagonists & inhibitors*; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D051381:Rats; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors*
D000577:Amides; D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D013844:Thiazoles; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases