RESUMO
A series of pantolactam based compounds were identified as potent antagonists for the androgen receptor (AR). Those that possessed properties suitable for topical delivery were evaluated in the validated Hamster Ear Model. Several compounds were found to be efficacious in reducing wax esters, a major component of sebum, initiating further preclinical work on these compounds.
Assuntos
Antagonistas de Receptores de Andrógenos/farmacologia , Ésteres/metabolismo , Lactamas/farmacologia , Sebo/efeitos dos fármacos , Ceras/metabolismo , Administração Tópica , Antagonistas de Receptores de Andrógenos/síntese química , Antagonistas de Receptores de Andrógenos/química , Animais , Cricetinae , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Ésteres/química , Lactamas/síntese química , Lactamas/química , Modelos Animais , Modelos Moleculares , Estrutura Molecular , Receptores Androgênicos/metabolismo , Sebo/metabolismo , Estereoisomerismo , Relação Estrutura-Atividade , Ceras/químicaRESUMO
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.
Assuntos
Antagonistas de Androgênios/farmacologia , Cabelo/crescimento & desenvolvimento , Hidrocarbonetos Fluorados/farmacologia , Nitrilas/farmacologia , Sebo , Animais , Cricetinae , Hidrocarbonetos Fluorados/farmacocinética , Masculino , Mesocricetus , Camundongos , Modelos Moleculares , Nitrilas/farmacocinéticaRESUMO
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.