Seco-prolinenitrile inhibitors of dipeptidyl peptidase IV define minimal pharmacophore requirements at P1

David R Magnin; Prakash C Taunk; James G Robertson; Aiying Wang; Jovita Marcinkeviciene; Mark S Kirby; Lawrence G Hamann

doi:10.1016/j.bmcl.2005.11.098

Seco-prolinenitrile inhibitors of dipeptidyl peptidase IV define minimal pharmacophore requirements at P1

Bioorg Med Chem Lett. 2006 Mar 15;16(6):1731-4. doi: 10.1016/j.bmcl.2005.11.098. Epub 2005 Dec 20.

Authors

David R Magnin¹, Prakash C Taunk, James G Robertson, Aiying Wang, Jovita Marcinkeviciene, Mark S Kirby, Lawrence G Hamann

Affiliation

¹ Department of Discovery Chemistry, Bristol-Myers Squibb, Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA.

PMID: 16376077
DOI: 10.1016/j.bmcl.2005.11.098

Abstract

A series of seco-prolinenitrile-containing dipeptides were synthesized and assayed as inhibitors of the N-terminal sequence-specific serine protease dipeptidyl peptidase IV, a promising new target for treatment of type 2 diabetes. The inhibitors described herein assess the minimum structural requirements at P1 for this enzyme, resulting in the identification of inhibitors with low nM potency.

MeSH terms

Adenosine Deaminase / chemistry*
Aniline Compounds / metabolism
Dipeptides* / chemical synthesis
Dipeptides* / chemistry
Dipeptides* / pharmacology
Dipeptidyl Peptidase 4 / chemistry*
Enzyme Inhibitors* / chemical synthesis
Enzyme Inhibitors* / chemistry
Enzyme Inhibitors* / pharmacology
Glycoproteins / chemistry*
Humans
Nitriles* / chemical synthesis
Nitriles* / chemistry
Nitriles* / pharmacology
Proline / chemistry*

Substances

Aniline Compounds
Dipeptides
Enzyme Inhibitors
Glycoproteins
Nitriles
nitroaniline
Proline
DPP4 protein, human
Dipeptidyl Peptidase 4
Adenosine Deaminase