Send to

Choose Destination

See 1 citation found by title matching your search:

Bioorg Med Chem. 2013 Apr 1;21(7):1749-55. doi: 10.1016/j.bmc.2013.01.062. Epub 2013 Feb 8.

Discovery of potent dipeptidyl peptidase IV inhibitors through pharmacophore hybridization and hit-to-lead optimization.

Author information

Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Science, 190 Kaiyuan Avenue, Guangzhou Science Park, Guangzhou 510530, China.


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).

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center