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Bioorg Med Chem ; 23(15): 4710-4718, 2015 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-26072172

RESUMEN

In this contribution the development of a new class of vasodilating compounds obtained by lead structure optimization is described. Three groups of compounds were synthesized and tested for their activity on various smooth muscle preparations of the guinea pig. Beside the lead compound 3a, the most interesting derivative was 1H-imidazole-1-carbothioic acid O-cyclohexyl ester hydrochloride (5b) with a good selective vasodilating potential on aorta and pulmonary artery rings (EC50 14 µM and 24 µM, respectively). Due to the properties of small molecules the hydrolysis behavior of the compounds can be easily adapted hence opening a new route in terms of duration of the agent's effect. With the aid of structure-activity relationship studies, structural motifs influencing the biological activity on isolated smooth muscle cell preparations of the synthesized compounds were proposed. The presented compounds offer good tools in identifying promising molecules as emergency therapy in myocardial infarction.


Asunto(s)
Músculo Liso Vascular/efectos de los fármacos , Urea/química , Vasodilatadores/química , Vasodilatadores/farmacología , Animales , Aorta/fisiología , Evaluación Preclínica de Medicamentos , Cobayas , Semivida , Hidrólisis , Espectroscopía de Resonancia Magnética , Contracción Muscular/efectos de los fármacos , Músculo Liso Vascular/fisiología , Arteria Pulmonar/fisiología , Relación Estructura-Actividad , Urea/metabolismo , Urea/farmacología , Vasodilatadores/metabolismo
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