2-arylaminothiazoles as high-affinity corticotropin-releasing factor 1 receptor (CRF1R) antagonists: synthesis, binding studies and behavioral efficacy.
2-arylamino-4-trifluoromethyl-5-aminomethylthiazoles represent a novel series of high-affinity corticotropin releasing factor-1 receptor (CRF(1)R) antagonists that are prepared in three steps in good overall yields. Herein, we report binding SAR as well as anxiolytic activity of an exemplary compound (7a, K(i)=8.6 nM) in a mouse canopy model.
Dubowchik
Gene M
GM
Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5100, Wallingford, CT 06492-7660, USA. dubowchik@bms.com
Michne
Jodi A
JA
Zuev
Dmitry
D
Schwartz
Wendy
W
Scola
Paul M
PM
James
Clint A
CA
Ruediger
Edward H
EH
Pin
Sokhom S
SS
Burris
Kevin D
KD
Balanda
Lynn A
LA
Gao
Qi
Q
Wu
Dedong
D
Fung
Lawrence
L
Fiedler
Tracey
T
Browman
Kaitlin E
KE
Taber
Matthew T
MT
Zhang
Jie
J
D000818:Animals; D001665:Binding Sites; D006801:Humans; D007700:Kinetics; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D000099052:CRF Receptor, Type 1
D018019:Receptors, Corticotropin-Releasing Hormone; D013844:Thiazoles; D000099052:CRF Receptor, Type 1