Bristol-Myers Squibb Research & Development, Wallingford, CT 06492, USA.
Bioorg Med Chem Lett. 2010 Mar 15;20(6):1905-9. doi: 10.1016/j.bmcl.2010.01.127. Epub 2010 Feb 4.
Several tetrahydroimidazopyrimidines were prepared using silver assisted cyclization as the key step. The binding affinities of compounds thus prepared were evaluated in vitro toward hCRF(1)R. Initial lead compound 16 (K(i)=32 nM) demonstrated modest putative anxiolytic effects in the mouse canopy test. Further optimization using parallel synthesis provided compounds with K(i)'s <50 nM.
几种四氢咪唑并嘧啶类化合物采用银辅助环化作为关键步骤进行制备。由此制备的化合物的体外结合亲和力针对 hCRF(1)R 进行了评估。初步先导化合物 16（K(i)=32 nM）在小鼠天篷测试中显示出适度的潜在抗焦虑作用。使用平行合成进行进一步优化提供了 K(i)'s<50 nM 的化合物。
