C-alkylated spiro[benzofuran-3(2H),4'-1'-methyl-piperidine-7-ols] as potent opioids: a conformation-activity study.

Article Details

Citation

Tsai YC, Liou JP, Liao R, Cheng CY, Tao PL

C-alkylated spiro[benzofuran-3(2H),4'-1'-methyl-piperidine-7-ols] as potent opioids: a conformation-activity study.

Bioorg Med Chem Lett. 1998 Jul 21;8(14):1813-8.

PubMed ID
9873439 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
MeperidineKappa-type opioid receptorKi (nM)>100000N/AN/ADetails
MeperidineMu-type opioid receptorKi (nM)451N/AN/ADetails
MorphineKappa-type opioid receptorKi (nM)1870N/AN/ADetails
MorphineMu-type opioid receptorKi (nM)38N/AN/ADetails