title: Synthesis and biological activity of 8beta-substituted hydrocodone indole and hydromorphone indole derivatives.
abstract: 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).
authors.affiliation: Laboratory of Medicinal Chemistry, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Han
authors.initials: H
authors.lastname: Yu
authors.forename: Thomas
authors.initials: T
authors.lastname: Prisinzano
authors.forename: Christina M
authors.initials: CM
authors.lastname: Dersch
authors.forename: Jamila
authors.initials: J
authors.lastname: Marcus
authors.forename: Richard B
authors.initials: RB
authors.lastname: Rothman
authors.forename: Arthur E
authors.initials: AE
authors.lastname: Jacobson
authors.forename: Kenner C
authors.initials: KC
authors.lastname: Rice
mesh_terms: D006853:Hydrocodone / Q000737:chemistry*; D004091:Hydromorphone / Q000737:chemistry*; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D007211:Indoles; D011957:Receptors, Opioid; D006853:Hydrocodone; D004091:Hydromorphone