Asunto(s)
Vasopresinas/síntesis química , Adenilil Ciclasas/metabolismo , Animales , Membrana Celular/metabolismo , Médula Renal/metabolismo , Receptores de Angiotensina/metabolismo , Receptores de Vasopresinas , Relación Estructura-Actividad , Porcinos , Vasopresinas/antagonistas & inhibidores , Vasopresinas/farmacologíaRESUMEN
Certain 6-halo-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines were found to be potent D-1 dopamine agonists. The 1-(4-hydroxyphenyl) analogues did not have central nervous system activity because their high polarity inhibited entry into the brain. However, these compounds were potent renal vasodilators. Fenoldopam, the 6-chloro analogue, is an especially significant member of the series, and its synthesis, pharmacology, and clinical properties have been studied extensively. The 6-methyl and 6-iodo congeners were potent renal vasodilators, but nonpotent partial D-1 agonists as measured by stimulation of rat caudate adenylate cyclase. A possible rationalization suggests different receptor reserves for these activities. The 9-substituted benzazepines were either inactive or of low potency as dopamine agonists, while the N-methyl analogues had significant antagonist potency as measured by inhibition of dopamine stimulation of rat caudate adenylate cyclase.
Asunto(s)
Benzazepinas/farmacología , Receptores Dopaminérgicos/efectos de los fármacos , Circulación Renal/efectos de los fármacos , Vasodilatadores/síntesis química , Adenilil Ciclasas/análisis , Animales , Presión Sanguínea/efectos de los fármacos , Encéfalo/efectos de los fármacos , Perros , Fenoldopam , Relación Estructura-Actividad , Vasodilatadores/farmacologíaAsunto(s)
Oligopéptidos/farmacología , Vasopresinas/antagonistas & inhibidores , Inhibidores de Adenilato Ciclasa , Animales , Médula Renal/enzimología , Lipresina/farmacología , Oligopéptidos/síntesis química , Oligopéptidos/metabolismo , Ratas , Receptores de Angiotensina/metabolismo , Receptores de Vasopresinas , Relación Estructura-Actividad , PorcinosRESUMEN
The title compound is a key intermediate for the preparation of oxytocin and vasopressin antagonists. Using sodium benzylmercaptide instead of boron trifluoride etherate as catalyst gives a better than four fold overall improvement in yield of the title compound from ethyl cyclohexylideneacetate and benzylmercaptan. The preparation of the corresponding acid labile S-p-methylbenzylmercapto and S-p-methoxybenzylmercapto analogs is also described.