Synthetic Organic & Medicinal Chemistry Laboratory (SOMCL), Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai, China.
J Med Chem. 2010 Feb 11;53(3):1319-28. doi: 10.1021/jm9015763.
A series of new aporphine analogues were synthesized and pharmacologically evaluated. 11-Allyloxy-(17), 11-propargyloxy-(20), and dihydrofuro-(19) aporphines displayed the highest affinity at the 5-HT(1A) receptor with K(i) values of 12.0, 14.0, and 6.7 nM, respectively. The high binding potential of the diastereomeric mixture of aporphine 19 was found residing in the cis-diastereomer (cis-19). [(35)S]GTP gamma S function assays on 5-HT(1A) receptor indicated that aporphines 17 and 20 were partial agonists, while trans-19 behaved as a high efficacy full antagonist and cis-19 was a full agonist. The agonistic property of cis-19 at the 5-HT(1A) receptor was further confirmed in vitro and in vivo. This compound may be useful as a potential treatment for anxiety.
一系列新的阿朴啡类似物被合成并进行了药理学评价。11-烯丙氧基-(17)、11-炔丙氧基-(20)和二氢呋喃-(19)阿朴啡在 5-HT(1A)受体上显示出最高的亲和力，其 K(i)值分别为 12.0、14.0 和 6.7 nM。阿朴啡 19 的非对映异构体混合物具有高的结合潜能，这归因于顺式-19。在 5-HT(1A)受体上进行的 [(35)S]GTPγS 功能测定表明，阿朴啡 17 和 20 为部分激动剂，而反式-19 表现为高效力的完全拮抗剂，顺式-19 则为完全激动剂。顺式-19 在 5-HT(1A)受体上的激动作用在体外和体内均得到了进一步证实。该化合物可能对焦虑症的治疗有帮助。
