Mono- and diaryl-2-quinuclidinylcarbinols with local anesthetic and antiarrhythmic activity

The reaction between 2-carboethoxyquinuclidine and various aryl- and heteroarylithium reagents gave mixtures of aryl 2-quinuclidinyl ketones and diaryl-2-quinuclidinylcarbinols. Diborane reduction of the ketones gave the erythro-carbinols, stereochemically analogous to quinidine. Several of the mono...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1980-02, Vol.23 (2), p.180-184
Main Authors: Nelson, P. H, Strosberg, A. M, Untch, K. G
Format: Article
Language:English
Subjects:
Anesthetics, Local - chemical synthesis
Animals
Anti-Arrhythmia Agents - chemical synthesis
Dogs
Female
Guinea Pigs
Ouabain - antagonists & inhibitors
Quinuclidines - chemical synthesis
Quinuclidines - pharmacology
Structure-Activity Relationship
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Summary:The reaction between 2-carboethoxyquinuclidine and various aryl- and heteroarylithium reagents gave mixtures of aryl 2-quinuclidinyl ketones and diaryl-2-quinuclidinylcarbinols. Diborane reduction of the ketones gave the erythro-carbinols, stereochemically analogous to quinidine. Several of the mono- and diarylcarbinols exhibited potent local anesthetic and antiarrhythmic activity, in some cases greater than that of quinidine. Diphenyl-2-quinuclidinylcarbinol and a (bromomethoxyphenyl)(methoxyphenyl)-2-quinuclidinylcarbinol were particularly active in reverting ouabain-induced arrhythmia in dogs, showing a potency and duration of action equal to or greater than that of propranolol.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00176a014