title: Redefining the structure-activity relationships of 2,6-methano-3-benzazocines. Part 8. High affinity ligands for opioid receptors in the picomolar Ki range: oxygenated N-(2-[1,1'-biphenyl]-4-ylethyl) analogues of 8-CAC.
abstract: N-[2-(4'-methoxy[1,1'-biphenyl]-4-yl)ethyl]-8-CAC (1) is a high affinity (K(i)=0.084 nM) ligand for the μ opioid receptor and served as the lead compound for this study. Analogues of 1 were made in hopes of identifying an SAR within a series of oxygenated (distal) phenyl derivatives. A number of new analogues were made having single-digit pM affinity for the μ receptor. The most potent was the 3',4'-methylenedioxy analogue 18 (K(i)=1.6 pM).
authors.affiliation: Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. wentmp@rpi.edu
authors.forename: Mark P
authors.initials: MP
authors.lastname: Wentland
authors.forename: Sunjin
authors.initials: S
authors.lastname: Jo
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Gargano
authors.forename: Melissa A
authors.initials: MA
authors.lastname: VanAlstine
authors.forename: Dana J
authors.initials: DJ
authors.lastname: Cohen
authors.forename: Jean M
authors.initials: JM
authors.lastname: Bidlack
mesh_terms: D003496:Cyclazocine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D010100:Oxygen / Q000737:chemistry*; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; C580965:N-(2-(4'-methoxy(1,1'-biphenyl)-4-yl)ethyl)-8-carboxamidocyclazocine; D017450:Receptors, Opioid, mu; D003496:Cyclazocine; D010100:Oxygen