RESUMEN
A series of amino-pyridines were synthesized and evaluated for androgen antagonist activities. Among these compounds, (R)-(+)-6-[methyl-(1-phenyl-ethyl)-amino]-4-trifluoromethyl-nicotinonitrile was the most active example of this class. This compound displayed potent androgen receptor antagonist activity as well as favorable pharmacokinetic characteristics for a potential topical agent. It also demonstrated remarkable potency for stimulating hair growth in a male C3H mouse model as well as reducing sebum production in the male Syrian hamster ear model.
Asunto(s)
Aminopiridinas/química , Aminopiridinas/farmacología , Antagonistas de Receptores Androgénicos , Cabello/efectos de los fármacos , Cabello/crecimiento & desarrollo , Sebo/efectos de los fármacos , Sebo/metabolismo , Aminopiridinas/síntesis química , Animales , Relación Dosis-Respuesta a Droga , Masculino , Ratones , Ratones Endogámicos C3H , Modelos Moleculares , Estructura Molecular , Receptores Androgénicos/metabolismo , Relación Estructura-ActividadRESUMEN
Synthesis, pharmacology, and pharmacokinetic profiles of (1R, 2S)-4-(2-cyano-cyclohexyl-oxy)-2-trifluoromethyl-benzonitrile are reported. This compound demonstrated remarkable potency for stimulating hair growth in a male C3H mouse model as well as reducing sebum production in the male Syrian hamster ear model.