Ponnala Shashikanth, Gonzales Junior, Kapadia Nirav, Navarro Hernan A, Harding Wayne W
Chemistry Dept., Hunter College, CUNY, 695 Park Avenue, NY 10065, USA.
Chemistry Dept., Hunter College, CUNY, 695 Park Avenue, NY 10065, USA; The Graduate Center, City University of New York, 365 5th Ave., NY 10016, USA.
Bioorg Med Chem Lett. 2014 Apr 1;24(7):1664-7. doi: 10.1016/j.bmcl.2014.02.066. Epub 2014 Mar 4.
A set of aporphine analogs related to nantenine was evaluated for antagonist activity at 5-HT2A and α1A adrenergic receptors. With regards to 5-HT2A receptor antagonism, a C2 allyl group is detrimental to activity. The chiral center of nantenine is not important for 5-HT2A antagonist activity, however the N6 nitrogen atom is a critical feature for 5-HT2A antagonism. Compound 12b was the most potent 5-HT2A aporphine antagonist identified in this study and has similar potency to previously identified aporphine antagonists 2 and 3. The ring A and N6 modifications examined were detrimental to α1A antagonism. A slight eutomeric preference for the R enantiomer of nantenine was observed in relation to α1A antagonism.
对一组与南天竹宁相关的阿朴啡类似物进行了5-HT2A和α1A肾上腺素能受体拮抗剂活性评估。关于5-HT2A受体拮抗作用，C2烯丙基对活性不利。南天竹宁的手性中心对5-HT2A拮抗剂活性并不重要，然而N6氮原子是5-HT2A拮抗作用的关键特征。化合物12b是本研究中鉴定出的最有效的5-HT2A阿朴啡拮抗剂，其效力与先前鉴定的阿朴啡拮抗剂2和3相似。所研究的A环和N6修饰对α1A拮抗作用不利。在α1A拮抗作用方面，观察到南天竹宁的R对映体有轻微的优映体偏好。
