TY - JOUR
T1 - C-alkylated spiro[benzofuran-3(2H),4'-1'-methyl-piperidine-7-ols] as potent opioids
T2 - A conformation-activity study
AU - Tsai, Ya Ching
AU - Liou, Jing Ping
AU - Liao, Richard
AU - Cheng, Chen Yu
AU - Tao, Pao Luh
PY - 1998/7/21
Y1 - 1998/7/21
N2 - Among a series of C-alkylated analogs of the weak μ 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 μ-affinities, with (±)-4 being almost as potent as (-)-morphine; while the trans 3'-methyl analog (±)-5 remained a weak μ- binder. Energy calculations and nmr data indicated that compounds 2-4 favor phenyl-axial conformations, while compounds 1 and 5 favor phenyl-equatorial conformations.
AB - Among a series of C-alkylated analogs of the weak μ 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 μ-affinities, with (±)-4 being almost as potent as (-)-morphine; while the trans 3'-methyl analog (±)-5 remained a weak μ- binder. Energy calculations and nmr data indicated that compounds 2-4 favor phenyl-axial conformations, while compounds 1 and 5 favor phenyl-equatorial conformations.
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U2 - 10.1016/S0960-894X(98)00318-7
DO - 10.1016/S0960-894X(98)00318-7
M3 - Article
C2 - 9873439
AN - SCOPUS:0032555178
SN - 0960-894X
VL - 8
SP - 1813
EP - 1818
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 14
ER -