School of Pharmacy, College of Medicine, National Taiwan University, Number 1, Jen-Ai Road, Taipei, Taiwan 10018, ROC.
J Med Chem. 2010 Feb 11;53(3):1392-6. doi: 10.1021/jm901503e.
A series of enantiomeric N-substituted 2,3,4,4a,5,6,7,7a-octahydro-1H-benzofuro[3,2-e]isoquinolines was synthesized. The (-)-enantiomers had much greater kappa-, mu-, and delta-opioid receptor binding affinity than the corresponding (+)-enantiomers. Compounds (-)-1a, (-)-1b, and (-)-1c displayed subnanomolar binding affinity for the mu-receptor, and (-)-1b had a high affinity for the kappa-receptor. Compound (-)-1a was a mu-partial agonist and kappa-antagonist. Compound (-)-1b was a potent neutral mu-antagonist (K(d) = 0.22 nM) and a kappa-partial agonist.
一系列对映体 N-取代的 2,3,4,4a,5,6,7,7a-八氢-1H-苯并呋喃[3,2-e]异喹啉被合成。（-）-对映体比相应的（+）-对映体具有更大的 κ、μ 和 δ-阿片受体结合亲和力。化合物（-）-1a、（-）-1b 和（-）-1c 对 μ-受体具有亚纳摩尔结合亲和力，并且（-）-1b 对 κ-受体具有高亲和力。化合物（-）-1a 是 μ-部分激动剂和 κ-拮抗剂。化合物（-）-1b 是一种有效的中性 μ-拮抗剂（K(d) = 0.22 nM）和 κ-部分激动剂。
