Yu Han, Prisinzano Thomas, Dersch Christina M, Marcus Jamila, Rothman Richard B, Jacobson Arthur E, Rice Kenner C
Laboratory of Medicinal Chemistry, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.
Bioorg Med Chem Lett. 2002 Jan 21;12(2):165-8. doi: 10.1016/s0960-894x(01)00689-8.
The 8beta-unsubstituted and substituted analogues of hydrocodone indole and hydromorphone indole were synthesized and their binding affinities to opioid receptors were determined. Introduction of an 8beta-methyl group into the indolomorphinan nucleus increased affinity at all opioid receptors. 6,7-Dehydro-4,5alpha-epoxy-8beta-methyl-6,7,2',3'-indolomorphinan (9) was found to be a delta antagonist with subnanomolar affinity (0.7 nM) for the delta-opioid receptor, and to have good delta-selectivity (mu/delta=322).
合成了氢可酮吲哚和氢吗啡酮吲哚的8β-未取代和取代类似物，并测定了它们与阿片受体的结合亲和力。在吲哚吗啡喃核中引入8β-甲基可增加对所有阿片受体的亲和力。发现6,7-脱氢-4,5α-环氧-8β-甲基-6,7,2',3'-吲哚吗啡喃（9）是一种对δ-阿片受体具有亚纳摩尔亲和力（0.7 nM）的δ拮抗剂，并且具有良好的δ选择性（μ/δ = 322）。
