title: C-alkylated spiro[benzofuran-3(2H),4'-1'-methyl-piperidine-7-ols] as potent opioids: a conformation-activity study.
abstract: Among a series of C-alkylated analogs of the weak mu opioid ligand spiro[benzofuran-3(2H),4'-1'-methylpiperidine-7-ol] (1), the 2-methyl, 2-ethyl, and cis 3'-methyl analogs, namely compounds (+/-)2, (+/-)-3, and (+/-)-4, showed much enhanced mu-affinities, with (+/-)-4 being almost as potent as (-)-morphine; while the trans 3'-methyl analog (+/-)-5 remained a weak mu-binder. Energy calculations and nmr data indicated that compounds 2-4 favor phenyl-axial conformations, while compounds 1 and 5 favor phenyl-equatorial conformations.
authors.affiliation: Institute of Pharmaceutical Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Y C
authors.initials: YC
authors.lastname: Tsai
authors.forename: J P
authors.initials: JP
authors.lastname: Liou
authors.forename: R
authors.initials: R
authors.lastname: Liao
authors.forename: C Y
authors.initials: CY
authors.lastname: Cheng
authors.forename: P L
authors.initials: PL
authors.lastname: Tao
mesh_terms: D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D017450:Receptors, Opioid, mu / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D010880:Piperidines; D017450:Receptors, Opioid, mu