2-Arylpyrimidines: novel CRF-1 receptor antagonists.
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.
Yoon
Taeyoung
T
Neurogen Corporation, 35 Northeast Industrial Road, Branford, CT 06405, USA.
De Lombaert
Stéphane
S
Brodbeck
Robbin
R
Gulianello
Michael
M
Krause
James E
JE
Hutchison
Alan
A
Horvath
Raymond F
RF
Ge
Ping
P
Kehne
John
J
Hoffman
Diane
D
Chandrasekhar
Jayaraman
J
Doller
Darío
D
Hodgetts
Kevin J
KJ
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
D011743:Pyrimidines; D018019:Receptors, Corticotropin-Releasing Hormone