Yoon Taeyoung, De Lombaert Stéphane, Brodbeck Robbin, Gulianello Michael, Krause James E, Hutchison Alan, Horvath Raymond F, Ge Ping, Kehne John, Hoffman Diane, Chandrasekhar Jayaraman, Doller Darío, Hodgetts Kevin J
Neurogen Corporation, 35 Northeast Industrial Road, Branford, CT 06405, USA.
Bioorg Med Chem Lett. 2008 Aug 15;18(16):4486-90. doi: 10.1016/j.bmcl.2008.07.063. Epub 2008 Jul 18.
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.
描述了一系列新型促肾上腺皮质激素释放因子-1（CRF-1）受体拮抗剂——2-芳基嘧啶的设计、合成及构效关系研究。研究了芳环和嘧啶核心上的取代基对CRF-1受体结合的影响。发现了许多K(i)值低于10 nM且亲脂性在中枢神经系统药物最低可接受范围内（cLogP<5）的化合物。
