Gao Y, Zong R, Campbell A, Kula N S, Baldessarini R J, Neumeyer J L
Section of Medicinal Chemistry, College of Pharmacy and Allied Health Professions, Northeastern University, Boston, Massachusetts 02115.
J Med Chem. 1988 Jul;31(7):1392-6. doi: 10.1021/jm00402a024.
The R-(-) and S-(+) enantiomers of 11-hydroxy-N-n-propylnoraporphine, (R)-3 and (S)-3, were synthesized in six steps from 1-(3-methoxy-2-nitrobenzyl)isoquinoline. Neuropharmacological evaluation of the R and S isomers (by affinity to dopamine receptor sites in rat brain tissues, induction of stereotyped behavior, and interaction with motor arousal induced by (R)-apomorphine in the rat) indicated that, similar to the 10,11-dihydroxy congener 2, both enantiomers can bind to dopamine receptors but that only (R)-3 activates them, whereas (S)-3 shows activity as a dopaminergic antagonist.
11-羟基-N-正丙基去甲阿朴啡的R-(-)和S-(+)对映体，即(R)-3和(S)-3，以1-(3-甲氧基-2-硝基苄基)异喹啉为原料，经六步反应合成。对R和S异构体进行神经药理学评估（通过检测其对大鼠脑组织中多巴胺受体位点的亲和力、诱导刻板行为以及与(R)-阿扑吗啡在大鼠中诱导的运动觉醒的相互作用）表明，与10,11-二羟基同系物2类似，两种对映体均可与多巴胺受体结合，但只有(R)-3能激活它们，而(S)-3表现出多巴胺能拮抗剂的活性。
