title: Design and synthesis of 3-(2-pyridyl)pyrazolo[1,5-a]pyrimidines as potent CRF1 receptor antagonists.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry and Department of Pharmacology, Neurocrine Biosciences, Inc., 10555 Science Center Drive, San Diego, CA 92129, USA. chuang@neurocrine.com
authors.forename: Charles Q
authors.initials: CQ
authors.lastname: Huang
authors.forename: Keith M
authors.initials: KM
authors.lastname: Wilcoxen
authors.forename: Dimitri E
authors.initials: DE
authors.lastname: Grigoriadis
authors.forename: James R
authors.initials: JR
authors.lastname: McCarthy
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
mesh_terms: 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
chemical_list: 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