Quantitative structure-activity relationships for N-[(N',N'-disubstituted-amino)acetyl]arylamines for local anesthetic activity and acute toxicity

The synthesis and physicochemical properties of a series of N-[N',N'-disubstituted-amino)acetyl]arylamines are described. A QSAR method is applied to local anesthetic activity and acute toxicity by means of a "nonclassic" substituent variation involving a modification on both ary...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1980-02, Vol.23 (2), p.184-193
Main Authors: Heymans, Francoise, Le Therizien, Laurence, Godfroid, Jean Jacques, Bessin, Pierre
Format: Article
Language:English
Subjects:
Amines - analysis
Amines - chemical synthesis
Amines - pharmacology
Amines - toxicity
Anesthetics, Local - chemical synthesis
Animals
Anti-Arrhythmia Agents - chemical synthesis
Chemical Phenomena
Chemistry, Physical
Cornea - drug effects
Lethal Dose 50
Mice
Models, Biological
Rabbits
Solubility
Structure-Activity Relationship
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Summary:The synthesis and physicochemical properties of a series of N-[N',N'-disubstituted-amino)acetyl]arylamines are described. A QSAR method is applied to local anesthetic activity and acute toxicity by means of a "nonclassic" substituent variation involving a modification on both aryl and amino moieties. The choice of the different parameters (partition coefficient, pKa, connectivity index, molar refraction, and molar volume) is discussed and their different methods of determination are described. Molar refraction is the parameter which explains best the variance of the local anesthetic activity, and the quadratic regression with MR leads to a "posteriori" synthesis of one compound with optimized activity. However, the partition coefficient is the most explicative parameter for intravenous toxicity.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00176a015