Stereochemical Studies on Medicinal Agents. 18. Absolute Configuration and Analgetic Potency of Trimeperidine Enantiomers

David Fries, Philip S Portoghese

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Enantiomers of tripmeperidine were prepared and the absolute configuration was determined by degradation of piperidinol [(+)-7] to (R)-3-dimethylamino-2-methylpropiophenone. The analgetic potency of the 2S,4S,5R isomer, (+)-13, is approximately equal to morphine and nine times that of its enantiomer. The absolute stereoselectivity of trimeperidine and that reported for α-prodine is qualitatively the same and the conformational features of the more potent enantiomers are also very similar. The results suggest that the antipodal stereoselectivity of trimeperidine is controlled primarily by the configuration and conformation of groups attached to the C-4 and C-5 chiral centers and that the 2-Me group plays a relatively minor role in the drug-receptor interaction. The present study lends further support to an earlier proposal that potency differences between enantiomeric 4-phenylpiperidines are due to the ability of the receptor to discriminate between the enantiotopic edges of the piperidine ring and to conformational factors.

Original languageEnglish (US)
Pages (from-to)990-993
Number of pages4
JournalJournal of Medicinal Chemistry
Volume17
Issue number9
DOIs
StatePublished - Sep 1 1974

Fingerprint

Promedol
Alphaprodine
Drug Receptors
Drug Interactions
Morphine

Cite this

@article{5102dd5b8df647e9b172af5c4a205186,
title = "Stereochemical Studies on Medicinal Agents. 18. Absolute Configuration and Analgetic Potency of Trimeperidine Enantiomers",
abstract = "Enantiomers of tripmeperidine were prepared and the absolute configuration was determined by degradation of piperidinol [(+)-7] to (R)-3-dimethylamino-2-methylpropiophenone. The analgetic potency of the 2S,4S,5R isomer, (+)-13, is approximately equal to morphine and nine times that of its enantiomer. The absolute stereoselectivity of trimeperidine and that reported for α-prodine is qualitatively the same and the conformational features of the more potent enantiomers are also very similar. The results suggest that the antipodal stereoselectivity of trimeperidine is controlled primarily by the configuration and conformation of groups attached to the C-4 and C-5 chiral centers and that the 2-Me group plays a relatively minor role in the drug-receptor interaction. The present study lends further support to an earlier proposal that potency differences between enantiomeric 4-phenylpiperidines are due to the ability of the receptor to discriminate between the enantiotopic edges of the piperidine ring and to conformational factors.",
author = "David Fries and Portoghese, {Philip S}",
year = "1974",
month = "9",
day = "1",
doi = "10.1021/jm00255a018",
language = "English (US)",
volume = "17",
pages = "990--993",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "9",

}

TY - JOUR

T1 - Stereochemical Studies on Medicinal Agents. 18. Absolute Configuration and Analgetic Potency of Trimeperidine Enantiomers

AU - Fries, David

AU - Portoghese, Philip S

PY - 1974/9/1

Y1 - 1974/9/1

N2 - Enantiomers of tripmeperidine were prepared and the absolute configuration was determined by degradation of piperidinol [(+)-7] to (R)-3-dimethylamino-2-methylpropiophenone. The analgetic potency of the 2S,4S,5R isomer, (+)-13, is approximately equal to morphine and nine times that of its enantiomer. The absolute stereoselectivity of trimeperidine and that reported for α-prodine is qualitatively the same and the conformational features of the more potent enantiomers are also very similar. The results suggest that the antipodal stereoselectivity of trimeperidine is controlled primarily by the configuration and conformation of groups attached to the C-4 and C-5 chiral centers and that the 2-Me group plays a relatively minor role in the drug-receptor interaction. The present study lends further support to an earlier proposal that potency differences between enantiomeric 4-phenylpiperidines are due to the ability of the receptor to discriminate between the enantiotopic edges of the piperidine ring and to conformational factors.

AB - Enantiomers of tripmeperidine were prepared and the absolute configuration was determined by degradation of piperidinol [(+)-7] to (R)-3-dimethylamino-2-methylpropiophenone. The analgetic potency of the 2S,4S,5R isomer, (+)-13, is approximately equal to morphine and nine times that of its enantiomer. The absolute stereoselectivity of trimeperidine and that reported for α-prodine is qualitatively the same and the conformational features of the more potent enantiomers are also very similar. The results suggest that the antipodal stereoselectivity of trimeperidine is controlled primarily by the configuration and conformation of groups attached to the C-4 and C-5 chiral centers and that the 2-Me group plays a relatively minor role in the drug-receptor interaction. The present study lends further support to an earlier proposal that potency differences between enantiomeric 4-phenylpiperidines are due to the ability of the receptor to discriminate between the enantiotopic edges of the piperidine ring and to conformational factors.

UR - http://www.scopus.com/inward/record.url?scp=0016258387&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0016258387&partnerID=8YFLogxK

U2 - 10.1021/jm00255a018

DO - 10.1021/jm00255a018

M3 - Article

VL - 17

SP - 990

EP - 993

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 9

ER -