RESUMO
A series of 1-alkyl-3-phenylthiourea analogues were prepared and evaluated as HDL- and Apo A-I-elevating and triglyceride-lowering agents. Several derivatives were superior to gemfibrozil. The optimal analogue (HDL376) was shown to raise HDL cholesterol in the rat, hamster, dog, and monkey models.
Assuntos
Genfibrozila/farmacologia , Lipoproteínas HDL/metabolismo , Feniltioureia/síntese química , Feniltioureia/farmacologia , Administração Oral , Animais , Centrifugação com Gradiente de Concentração , HDL-Colesterol/metabolismo , Cromatografia Líquida de Alta Pressão , Cricetinae , Cães , Avaliação Pré-Clínica de Medicamentos , Haplorrinos , Lipídeos/química , Masculino , Modelos Químicos , Feniltioureia/administração & dosagem , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Triglicerídeos/metabolismoRESUMO
A series of 1-hydroxyalkyl-3-phenylthiourea analogs were prepared and evaluated as HDL-and Apo A-I-elevating agents. Derivatives 5h, 7j, 7n, and 7o were found to be as effective or superior to gemfibrozil.
Assuntos
Lipoproteínas HDL/efeitos dos fármacos , Feniltioureia/análogos & derivados , Feniltioureia/farmacologia , Animais , Apolipoproteína A-I/sangue , Apolipoproteína A-I/efeitos dos fármacos , Colesterol/administração & dosagem , Colesterol/sangue , Humanos , Lipídeos/sangue , Lipoproteínas HDL/sangue , Masculino , Feniltioureia/síntese química , Ratos , Relação Estrutura-Atividade , Aumento de Peso/efeitos dos fármacosRESUMO
A series of gemfibrozil analogues with a thiourea moiety embedded in the side chain was prepared and evaluated as HDL-elevating agents. Derivatives 8b, 9b, 9c, and 9d were found to be approximately as effective as gemfibrozil (1) for HDL cholesterol elevation.
