RESUMO
A method for detecting glutathione selectively in whole blood deposited on filter paper is described. GSH is fractionated from proteins, hemoglobin and other potentially interfering components and determined using a resorufin-acrylate fluorescent probe. The relative standard deviation is lower than 5% (n = 5). Recoveries of GSH from whole blood are between 94% and 108.6%.
Assuntos
Análise Química do Sangue/métodos , Glutationa/sangue , Corantes Fluorescentes/química , Glutationa/química , Humanos , Concentração de Íons de Hidrogênio , Oxazinas/químicaRESUMO
Utilizing structure-based drug design, a novel dihydropyridopyrimidinone series which exhibited potent Hsp90 inhibition, good pharmacokinetics upon oral administration, and an excellent pharmacokinetic/pharmacodynamic relationship in vivo was developed from a commercial hit. The exploration of this series led to the selection of NVP-HSP990 as a development candidate.
Assuntos
Antineoplásicos/síntese química , Piridonas/síntese química , Pirimidinas/síntese química , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Camundongos , Piridonas/farmacocinética , Piridonas/farmacologia , Pirimidinas/farmacocinética , Pirimidinas/farmacologia , Relação Estrutura-AtividadeRESUMO
Substituted acrylamides were used as templates that bridge P1 and P4 binding elements, resulting in a series of potent (sub-nanomolar) and selective factor Xa inhibitors. In this template, cis-geometry of P1 and P4 ligands is highly preferred. SAR on the substituting groups, as well as on modification of P1 and P4 moieties is described. Compounds in this series show good in vivo efficacy in animal models.
