title: Synthesis of new opioid derivatives with a propellane skeleton and their pharmacology: part 1.
abstract: The observation that 17-cyclopropylmethylmorphinan derivatives without the 4,5-epoxy ring showed more κ selectivity than those with a 4,5-epoxy ring led us to develop a working hypothesis: the position of the plane composed of the A and B rings would influence the opioid receptor type selectivity and that the decrease in the torsion angle C11-C12-C13-C14 could improve the κ selectivity. Consistent with our hypothesis, KNT-42 with an N-cyclopropylmethyl propellane structure, whose A and B rings were fixed in a torsion angle of approximately 0°, showed κ selective agonist activity.
authors.affiliation: School of Pharmacy, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Naoshi
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Hideaki
authors.initials: H
authors.lastname: Fujii
authors.forename: Toru
authors.initials: T
authors.lastname: Nemoto
authors.forename: Ryo
authors.initials: R
authors.lastname: Nakajima
authors.forename: Shinobu
authors.initials: S
authors.lastname: Momen
authors.forename: Naoki
authors.initials: N
authors.lastname: Izumimoto
authors.forename: Ko
authors.initials: K
authors.lastname: Hasebe
authors.forename: Hidenori
authors.initials: H
authors.lastname: Mochizuki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagase
mesh_terms: D000701:Analgesics, Opioid / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D051379:Mice; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects; D017473:Receptors, Opioid, kappa / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D000701:Analgesics, Opioid; D001952:Bridged-Ring Compounds; C562365:KNT 42; D017473:Receptors, Opioid, kappa