title: 2-Arylpyrimidines: novel CRF-1 receptor antagonists.
abstract: The design, synthesis and structure-activity relationship studies of a novel series of CRF-1 receptor antagonists, the 2-arylpyrimidines, are described. The effects of substitution on the aromatic ring and the pyrimidine core on CRF-1 receptor binding were investigated. A number of compounds with K(i) values below 10 nM and lipophilicity in a minimally acceptable range for a CNS drug (cLogP<5) were discovered.
authors.affiliation: Neurogen Corporation, 35 Northeast Industrial Road, Branford, CT 06405, USA.
authors.forename: Taeyoung
authors.initials: T
authors.lastname: Yoon
authors.forename: Stéphane
authors.initials: S
authors.lastname: De Lombaert
authors.forename: Robbin
authors.initials: R
authors.lastname: Brodbeck
authors.forename: Michael
authors.initials: M
authors.lastname: Gulianello
authors.forename: James E
authors.initials: JE
authors.lastname: Krause
authors.forename: Alan
authors.initials: A
authors.lastname: Hutchison
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Horvath
authors.forename: Ping
authors.initials: P
authors.lastname: Ge
authors.forename: John
authors.initials: J
authors.lastname: Kehne
authors.forename: Diane
authors.initials: D
authors.lastname: Hoffman
authors.forename: Jayaraman
authors.initials: J
authors.lastname: Chandrasekhar
authors.forename: Darío
authors.initials: D
authors.lastname: Doller
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Hodgetts
mesh_terms: D000818:Animals; D001665:Binding Sites; D002626:Chemistry, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D015195:Drug Design; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D008968:Molecular Conformation; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D012995:Solubility; D013329:Structure-Activity Relationship
chemical_list: D011743:Pyrimidines; D018019:Receptors, Corticotropin-Releasing Hormone