RESUMEN
During an effort to search for more potent growth hormone secretagogues, we discovered a class of compounds of which the best compound 8 was 7-fold more active in vitro than the best compound in the series we revealed before [Tata, J. R.; Lu, Z.; Jacks, T. M.; Schleim, K. D.; Cheng, K.; Wei, L.; Chan, W.-S.; Butler, B.; Tsou, N.; Leung, K.; Chiu, S.-H. L.; Hickey, G. J.; Smith, R. G.; Patchett, A. A. Bioorg. Med. Chem. Lett.1997, 7, 2319.]. Animal studies show that compound 8 can stimulate growth hormone release at the oral dose as low as 0.06 mpk. Chemistry and biological studies are discussed.
Asunto(s)
Química Farmacéutica/métodos , Hormona del Crecimiento/química , Hormona del Crecimiento/síntesis química , Administración Oral , Amidas/química , Aminas/química , Animales , Perros , Diseño de Fármacos , Evaluación Preclínica de Medicamentos , Hormona del Crecimiento/metabolismo , Indoles/farmacología , Modelos Químicos , Hipófisis/química , Hipófisis/citología , Hipófisis/efectos de los fármacos , Ratas , Compuestos de Espiro/farmacología , Relación Estructura-ActividadRESUMEN
A new series of growth hormone secretagogues have been discovered. The best compound, 26j, shows excellent ability to release growth hormone both in vitro and in vivo. The synthesis and biological activity of these compounds are discussed.