Your browser doesn't support javascript.
loading
Discovery of potent dipeptidyl peptidase IV inhibitors through pharmacophore hybridization and hit-to-lead optimization.
Zeng, Shaogao; Xie, Hui; Zeng, Li-li; Lu, Xin; Zhao, Xin; Zhang, Gui-cheng; Tu, Zheng-chao; Xu, Hong-jiang; Yang, Ling; Zhang, Xi-quan; Hu, Wenhui.
Afiliação
  • Zeng S; Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science, 190 Kaiyuan Avenue, Guangzhou Science Park, Guangzhou 510530, China.
Bioorg Med Chem ; 21(7): 1749-55, 2013 Apr 01.
Article em En | MEDLINE | ID: mdl-23434133
A novel dipeptidyl peptidase IV inhibitor hit (5, IC50=0.86 µM) was structurally derived from our recently disclosed preclinical candidate 4 by replacing the cyanobenzyl with a butynyl based on pharmacophore hybridization. A hit-to-lead optimization effort was then initiated to improve its potency. Most N-substituted analogs exhibited good in vitro activity, and compound 18o (IC50=1.55 nM) was identified to be a potent dipeptidyl peptidase IV inhibitor with a significantly improved pharmacokinetic properties (bioavailablity: 41% vs 82.9%; T1/2: 2h vs 4.9h).
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dipeptidil Peptidase 4 / Inibidores da Dipeptidil Peptidase IV Limite: Animals / Humans / Male Idioma: En Revista: Bioorg Med Chem Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2013 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dipeptidil Peptidase 4 / Inibidores da Dipeptidil Peptidase IV Limite: Animals / Humans / Male Idioma: En Revista: Bioorg Med Chem Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2013 Tipo de documento: Article País de afiliação: China