Cruse S F, Lear J, Klein C L, Andersen P H, Dick R M, Crider A M
School of Pharmacy, Northeast Louisiana University, Monroe 71209-0470.
J Pharm Sci. 1993 Mar;82(3):334-9. doi: 10.1002/jps.2600820324.
cis-1,2,3a,4,5,9b-Hexahydro-3H-benz[e]indoles were synthesized and evaluated for in vitro dopamine D1 and D2 receptor binding affinity. The target compounds 21-25 were readily prepared by reduction of the air-sensitive tricyclic enamines 10-14. Reduction of 10-14 with sodium borohydride, sodium cyanoborohydride, palladium on carbon in ethanol, and platinum oxide in ethanol or acetic acid gave only the cis (3a,9b) 1,2,3a,4,5,9b-hexahydro-3H-benz[e]indoles. The stereochemistry was confirmed by single-crystal X-ray analysis. In the 6-hydroxy series, the binding affinity at D1 and D2 receptors was of the order 22 (N-n-butyl) > 21 (N-n-propyl) > 23 (N-H). The compounds demonstrated greater binding affinity at D2 receptors than at D1 binding sites. In contrast, 8-OH derivatives exhibited affinity only for D2 receptors, with 25 (N-n-butyl) having slightly greater affinity than 24 (N-n-propyl).
顺式-1,2,3a,4,5,9b-六氢-3H-苯并[e]吲哚已被合成，并对其体外多巴胺D1和D2受体结合亲和力进行了评估。目标化合物21-25可通过还原对空气敏感的三环烯胺10-14轻松制备。用硼氢化钠、氰基硼氢化钠、乙醇中的钯-碳以及乙醇或乙酸中的氧化铂还原10-14，仅得到顺式(3a,9b) 1,2,3a,4,5,9b-六氢-3H-苯并[e]吲哚。其立体化学通过单晶X射线分析得以证实。在6-羟基系列中，D1和D2受体的结合亲和力顺序为22（N-正丁基）> 21（N-正丙基）> 23（N-H）。这些化合物在D2受体上的结合亲和力大于在D1结合位点上的亲和力。相比之下，8-OH衍生物仅对D2受体表现出亲和力，其中25（N-正丁基）的亲和力略大于24（N-正丙基）。
