RESUMEN
Molecular design, synthesis, in vitro and in vivo studies of novel derivatives of indole-3-carboxylic acid new series of angiotensin II receptor 1 antagonists is presented. Radioligand binding studies using [125I]-angiotensin II displayed that new derivatives of indole-3-carboxylic acid have a high nanomolar affinity for the angiotensin II receptor (AT1 subtype) on a par with the known pharmaceuticals such as losartan. Biological studies of synthesized compounds in spontaneously hypertensive rats have demonstrated that compounds can lower blood pressure when administered orally. Maximum the decrease in blood pressure was 48 mm Hg with oral administration of 10 mg/kg and antihypertensive effect was observed for 24 h, which is superior to losartan.
Asunto(s)
Antihipertensivos , Hipertensión , Ratas , Animales , Antihipertensivos/farmacología , Antihipertensivos/uso terapéutico , Losartán/farmacología , Hipertensión/tratamiento farmacológico , Antagonistas de Receptores de Angiotensina/química , Antagonistas de Receptores de Angiotensina/farmacología , Presión Sanguínea , Ratas Endogámicas SHR , Receptores de Angiotensina/metabolismo , Angiotensina II/farmacología , Tetrazoles/química , Compuestos de Bifenilo/químicaRESUMEN
We herein report new 5-substituted uridine derivatives as potent inhibitors of mycobacteria - causative agents of tuberculosis. A series of new 5-alkynyl-substituted uridine derivatives were synthesised via palladium-catalysed Sonogashira cross-coupling reaction of 5-iodo-6-methylpyrimidine base with terminal acetylenes with good yields in DMF at room temperature. It was found that methyl group in C-6 position of pyrimidine ring had no impact on yields of target compounds. All obtained compounds were evaluated for their antimycobacterial activity against Mycobacetrium bovis and Mycobacterium tuberculosis at concentrations of 1-100 µg/ml using MABA test. Synthesized nucleosides showed high antimycobacterial activity against M. bovis and M. Tuberculosis. The MIC50 values of 11 and 13 were similar or close to that of the reference drug rifampicin.
Asunto(s)
Antituberculosos/farmacología , Diseño de Fármacos , Mycobacterium bovis/efectos de los fármacos , Mycobacterium tuberculosis/efectos de los fármacos , Nucleósidos de Pirimidina/farmacología , Antituberculosos/síntesis química , Antituberculosos/química , Relación Dosis-Respuesta a Droga , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Nucleósidos de Pirimidina/síntesis química , Nucleósidos de Pirimidina/química , Relación Estructura-ActividadRESUMEN
Acute myocardial infarction is still considered as one of the most threatening disorders in internal medicine. Numerous complications of infarction develop due to activation of different neurohumoral systems. The article discusses modern methods of pharmacological correction of neurohumoral system activity in various stages of myocardial infarction. It is emphasized that current guidelines do not always allow to effectively prevent left ventricular remodeling. New drugs used for this aim are discussed.
