Design and synthesis of 3-(2-pyridyl)pyrazolo[1,5-a]pyrimidines as potent CRF1 receptor antagonists.
A series of 3-(2-pyridyl)pyrazolo[1,5-a]pyrimidines was designed and synthesized as antagonists for the corticotrophin-releasing factor-1 (CRF(1)) receptor. Several compounds such as 20c (K(i)=10 nM) exhibited good binding affinities at the CRF(1) receptor. In addition, 20c had adequate solubility in water.
Huang
Charles Q
CQ
Department of Medicinal Chemistry and Department of Pharmacology, Neurocrine Biosciences, Inc., 10555 Science Center Drive, San Diego, CA 92129, USA. chuang@neurocrine.com
Wilcoxen
Keith M
KM
Grigoriadis
Dimitri E
DE
McCarthy
James R
JR
Chen
Chen
C
D015195:Drug Design; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D000099052:CRF Receptor, Type 1
C417190:4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)pyrazolo(1,5-a)pyrimidine; D011720:Pyrazoles; D011743:Pyrimidines; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1