RESUMO
A series of 6-(4-amino-1-piperidinyl)carbonyl-2(1H)-quinolinones, and their open form derivatives, were synthesized and evaluated for their ability to stimulate femoral artery blood flow (FBF) in the canine hindlimb. All members of this series stimulated FBF, and subsequent experiments revealed that selected members of this series produced minimal changes in coronary blood flow or systemic blood pressure. Compound 25 was the most promising agent in this respect, and clinical trials are now ongoing to evaluate the effectiveness of this drug as a novel treatment for intermittent claudication and Raynaud's phenomenon.
Assuntos
Membro Posterior/irrigação sanguínea , Piperidinas/síntese química , Vasodilatadores/síntese química , Animais , Artérias , Pressão Sanguínea/efeitos dos fármacos , Circulação Coronária/efeitos dos fármacos , Cães , Fêmur/irrigação sanguínea , Técnicas In Vitro , Piperidinas/química , Piperidinas/farmacologia , Quinolonas/síntese química , Quinolonas/química , Quinolonas/farmacologia , Fluxo Sanguíneo Regional/efeitos dos fármacos , Relação Estrutura-Atividade , Vasodilatadores/química , Vasodilatadores/farmacologiaRESUMO
The synthesis of 3,4-diethoxybenzthioamide, the key intermediate for OPC-6535, is achieved by employing Friedel-Crafts reaction of 1,2-diethoxybenzene with potassium thiocyanate in methanesulfonic acid at ambient temperature.
