Stereochemistry and biological activity of the novel narcotic analgesic fenaridine

Fentanyl-Related Compounds and Derivatives: Current Status and Future Prospects for Pharmaceutical Applications

“…Obtained data indicate that only 3-methylation has a major effect for enhancing analgesic potency, whereas 2-methyl or 2,5-dimethyl substitution is detrimental to analgesic activity. However, comparison with data obtained by other groups suggested this data may not be correct [84–88]. …”

“…Three isomers have been separated chromatographically and investigated by NMR spectroscopy which revealed that the isomers differ in orientation of the methyl groups in the piperidine ring. In the first one (45% content of the obtained isomeric mixture) the methyl groups oriented as 2-equatorial-5-axial, in the second (40% content) both are equatorial, and in the third one (15%), both methyl groups are oriented axial [86–88]. Absolute configuration of isomers by x-ray investigations was determined [91,92].…”

“…The overall analgesic activity was comparable to that of fentanyl. Phenaridine itself (mixture of isomers) has an ED 50 value of 0.0048 mg/kg (rats, subcutaneous, tail flick test; duration of action 35 min) [88]. …”

DARK Classics in Chemical Neuroscience: Fentanyl

“…Expanding or contracting the piperidine ring by one carbon significantly decreases antinociceptive potency relative to that of fentanyl; however, the activity of resulting analogues remains comparable to that of morphine. ,, A series of analogues was created through methyl or hydroxyl substitution at each modifiable group on the fentanyl scaffold. Methyl substitutions on the piperidine ring, as seen in 3-methyl fentanyl and 2,5-dimethyl fentanyl (Figure ), have been shown to be extremely potent and have minimal variance in analgesic activity among isomers. , Two amide analogues, acrylfentanyl and furanylfentanyl, are fentanyl analogues that have re-emerged as designer drugs. Acrylfentanyl was originally developed to be a covalent MOR probe and contains a highly reactive acrylamide toxicophore .…”

“…Methyl substitutions on the piperidine ring, as seen in 3-methyl fentanyl and 2,5-dimethyl fentanyl (Figure 2), have been shown to be extremely potent and have minimal variance in analgesic activity among isomers. 47,48 Two amide analogues, acrylfentanyl and furanylfentanyl, are fentanyl analogues that have re-emerged as designer drugs. Acrylfentanyl was originally developed to be a covalent MOR probe and contains a highly reactive acrylamide toxicophore.…”