Linked Life Data

2213833

Source:http://linkedlifedata.com/resource/pubmed/id/2213833

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1990-11-20
pubmed:abstractText
Herein we describe a Free-Wilson/Fujita-Ban QSAR (quantitative structure-activity relationship) analysis of the analgesic potency of over 50 semisynthetic opioid narcotics. The 3-hydroxy- and 3-methoxy-N-alkylmorphinan-6-ones of B/C-cis and -trans stereochemistry include compounds exhibiting structural variation at five positions [N-methyl (C17), oxygen at C3, C4-C5 oxygen bridge, alkyl substituents at C7 and C8]. The pharmacological parameter correlated was the analgesic potency (-log ED50) exhibited on abdominal contractions produced by acetylcholine injection in mice. A satisfactory correlation was obtained only by assuming interdependent contributions of the substituents on C17 and O(C3), with which it was possible to explain 75% of the variance. Phenolic compounds (3-OH) behave somewhat differently from the methyl ethers (3-OCH3), and in both series the substituents on C8 have a size-dependent negative contribution, implying steric hindrance at their contact point on the receptor. With use of this correlation the potency of five further members of the series was predicted. Subsequent testing fully confirmed the validity of the correlation since the measured potencies were, within experimental error, equal to those calculated. In a further refinement, phenolic compounds were considered separately from the ethers, and it was found that the contribution of the substituents on C17, C7, and C8 remained similar in sign and magnitude but not that of the furan oxygen. This analysis allows us to conclude that if both phenolic and nonphenolic members of this series act on the same receptor they must bind at different subsites or in alternate modes, supporting an earlier proposal in the literature.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2813-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
A Free-Wilson/Fujita-Ban analysis and prediction of the analgesic potency of some 3-hydroxy- and 3-methoxy-N-alkylmorphinan-6-one opioids.
pubmed:affiliation
Departamento de Farmacología y Toxicología, Instituto Politécnico Nacional, México, D.F.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't