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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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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container_title Journal of medicinal chemistry
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creator Nelson, P. H
Strosberg, A. M
Untch, K. G
description 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.
doi_str_mv 10.1021/jm00176a014
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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.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm00176a014</identifier><identifier>PMID: 7359531</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Anesthetics, Local - chemical synthesis ; Animals ; Anti-Arrhythmia Agents - chemical synthesis ; Dogs ; Female ; Guinea Pigs ; Ouabain - antagonists &amp; inhibitors ; Quinuclidines - chemical synthesis ; Quinuclidines - pharmacology ; Structure-Activity Relationship</subject><ispartof>Journal of medicinal chemistry, 1980-02, Vol.23 (2), p.180-184</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a269t-7034039c7ec6bfd06ed6b63d9a37ec10db6670ad4d78060c546b55e9219b10eb3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jm00176a014$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm00176a014$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,27064,27924,27925,56766,56816</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7359531$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nelson, P. 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source ACS CRKN Legacy Archives
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
title Mono- and diaryl-2-quinuclidinylcarbinols with local anesthetic and antiarrhythmic activity
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