C-ALKYLATED RO[BENZOFURAN-3(2H),4'-1'-METHYL-PIPERIDINE-7-OLS] AS POTENT OPIOIDS - A CONFORMATION-ACTIVITY STUDY

Authors
TSAI YC LIOU JP LIAO R CHENG CY TAO PL
Citation
Yc. Tsai et al., C-ALKYLATED RO[BENZOFURAN-3(2H),4'-1'-METHYL-PIPERIDINE-7-OLS] AS POTENT OPIOIDS - A CONFORMATION-ACTIVITY STUDY, Bioorganic & medicinal chemistry letters, 8(14), 1998, pp. 1813-1818
Citations number
11
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
8
Issue
14
Year of publication
1998
Pages
1813 - 1818
Database
ISI
SICI code
0960-894X(1998)8:14<1813:CRAP>2.0.ZU;2-7
Abstract
Among a series of C-alkylated analogs of the weak mu opioid ligand spi ro[benzofuran-3(2H),4'-1'methylpiperidine-7-ol] (1), the 2-methyl, 2-e thyl, and cis 3'-methyl analogs, namely compounds (+/-)2, (+/-)-3, and (+/-)-4, showed much enhanced mu-affinities, with (+/-)-4 being almos t 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. (C) 1998 Elsevier Scienc e Ltd. All rights reserved.