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- 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.
D000779:Anesthetics, Local / Q000138:chemical synthesis*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis*; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D010042:Ouabain / Q000037:antagonists & inhibitors; D011812:Quinuclidines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000779:Anesthetics, Local; D000889:Anti-Arrhythmia Agents; D011812:Quinuclidines; D010042:Ouabain