Dounay Amy B, Barta Nancy S, Bikker Jack A, Borosky Susan A, Campbell Brian M, Crawford Terry, Denny Lynne, Evans Lori M, Gray David L, Lee Pil, Lenoir Edward A, Xu Wenjian
Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, United States.
Bioorg Med Chem Lett. 2009 Feb 15;19(4):1159-63. doi: 10.1016/j.bmcl.2008.12.087. Epub 2008 Dec 25.
Aminopyrimidine 2 (4-(1-(2-(1H-indol-3-yl)ethyl)piperidin-3-yl)-N-cyclopropylpyrimidin-2-amine) emerged from a high throughput screen as a novel 5-HT(1A) agonist. This compound showed moderate potency for 5-HT(1A) in binding and functional assays, as well as moderate metabolic stability. Implementation of a strategy for improving metabolic stability by lowering the lipophilicity (cLogD) led to identification of methyl ether 31 (4-(1-(2-(1H-indol-3-yl)ethyl)piperidin-3-yl)-N-(2-methoxyethyl)pyrimidin-2-amine) as a substantially improved compound within the series.
氨基嘧啶2（4-(1-(2-(1H-吲哚-3-基)乙基)哌啶-3-基)-N-环丙基嘧啶-2-胺）是通过高通量筛选发现的新型5-HT(1A)激动剂。该化合物在结合和功能测定中对5-HT(1A)表现出中等效力，且具有中等代谢稳定性。通过降低亲脂性（cLogD）来提高代谢稳定性的策略实施后，得到了甲基醚31（4-(1-(2-(1H-吲哚-3-基)乙基)哌啶-3-基)-N-(2-甲氧基乙基)嘧啶-2-胺），它是该系列中显著改进的化合物。
