[(S)-gamma-(4-Aryl-1-piperazinyl)-l-prolyl]thiazolidines as a novel series of highly potent and long-lasting DPP-IV inhibitors

Tomohiro Yoshida; Hiroshi Sakashita; Fumihiko Akahoshi; Yoshiharu Hayashi

doi:10.1016/j.bmcl.2007.01.110

[(S)-gamma-(4-Aryl-1-piperazinyl)-l-prolyl]thiazolidines as a novel series of highly potent and long-lasting DPP-IV inhibitors

Bioorg Med Chem Lett. 2007 May 1;17(9):2618-21. doi: 10.1016/j.bmcl.2007.01.110. Epub 2007 Feb 8.

Authors

Tomohiro Yoshida¹, Hiroshi Sakashita, Fumihiko Akahoshi, Yoshiharu Hayashi

Affiliation

¹ Chemistry Laboratory, Pharmaceuticals Research Division, Mitsubishi Pharma Corporation, 1000, Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan.

PMID: 17317162
DOI: 10.1016/j.bmcl.2007.01.110

Abstract

In the search for an inhibitor of dipeptidyl peptidase IV (DPP-IV) highly potent both in vitro and in vivo, we synthesized a series of L-prolylthiazolidine-based DPP-IV inhibitors having 4-arylpiperazine or 4-arylpiperidine at the gamma-position of the proline structure. Of these compounds, the 4-(5-nitro-2-pyridyl)piperazine analog 21e showed a sub-nanomolar (IC(50)=0.92 nmol/L) DPP-IV inhibitory activity and a long-lasting in vivo DPP-IV inhibition profile.

MeSH terms

Animals
Chemistry, Pharmaceutical / methods*
Diabetes Mellitus, Type 2 / drug therapy
Dipeptidyl-Peptidase IV Inhibitors*
Drug Design
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology*
Inhibitory Concentration 50
Models, Chemical
Molecular Conformation
Piperazine
Piperazines / chemistry
Piperazines / pharmacology*
Rats
Rats, Wistar
Structure-Activity Relationship
Thiazolidines / pharmacology*
Time Factors

Substances

Dipeptidyl-Peptidase IV Inhibitors
Enzyme Inhibitors
Piperazines
Thiazolidines
Piperazine