Trivedi B K, Bruns R F
Department of Chemistry, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105.
J Med Chem. 1988 May;31(5):1011-4. doi: 10.1021/jm00400a021.
Several [1,2,4]triazolo[4,3-a]quinoxalines that were reported as antidepressants in the patent literature were found to possess moderate affinity for the adenosine A1 and A2 receptors. On the basis of structural parallels with adenine and adenosine, the N-cyclopentyl derivative was synthesized and found to have improved affinity and selectivity for the A1 receptor. In the N-cyclopentyl series, affinity was optimal with trifluoromethyl substitution at the 1-position, resulting in a compound (9) with 7.3 nM A1 affinity and 138-fold selectivity for the A1 receptor.
专利文献中报道的几种作为抗抑郁药的[1,2,4]三唑并[4,3 - a]喹喔啉被发现对腺苷A1和A2受体具有中等亲和力。基于与腺嘌呤和腺苷的结构相似性，合成了N - 环戊基衍生物，发现其对A1受体具有更高的亲和力和选择性。在N - 环戊基系列中，1位上的三氟甲基取代时亲和力最佳，得到一种化合物（9），其对A1受体的亲和力为7.3 nM，选择性为138倍。
