Triazolopiperazine-amides as dipeptidyl peptidase IV inhibitors: close analogs of JANUVIA (sitagliptin phosphate)

Dooseop Kim; Jennifer E Kowalchick; Scott D Edmondson; Anthony Mastracchio; Jinyou Xu; George J Eiermann; Barbara Leiting; Joseph K Wu; KellyAnn D Pryor; Reshma A Patel; Huaibing He; Kathryn A Lyons; Nancy A Thornberry; Ann E Weber

doi:10.1016/j.bmcl.2007.03.098

Triazolopiperazine-amides as dipeptidyl peptidase IV inhibitors: close analogs of JANUVIA (sitagliptin phosphate)

Bioorg Med Chem Lett. 2007 Jun 15;17(12):3373-7. doi: 10.1016/j.bmcl.2007.03.098. Epub 2007 Apr 5.

Authors

Dooseop Kim¹, Jennifer E Kowalchick, Scott D Edmondson, Anthony Mastracchio, Jinyou Xu, George J Eiermann, Barbara Leiting, Joseph K Wu, KellyAnn D Pryor, Reshma A Patel, Huaibing He, Kathryn A Lyons, Nancy A Thornberry, Ann E Weber

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. dooseop_kim@merck.com

PMID: 17434732
DOI: 10.1016/j.bmcl.2007.03.098

Abstract

A series of beta-aminoamides bearing triazolopiperazines has been prepared and evaluated as potent, selective, orally active dipeptidyl peptidase IV (DPP-4) inhibitors. Efforts at optimization of the beta-aminoamide series, which ultimately led to the discovery of JANUVIA (sitagliptin phosphate, compound 1), are described.

MeSH terms

Amides / chemistry*
Animals
Dipeptidyl-Peptidase IV Inhibitors*
Piperazines / chemistry*
Protease Inhibitors / chemical synthesis
Protease Inhibitors / pharmacology*
Pyrazines / chemistry
Pyrazines / pharmacology*
Rats
Sitagliptin Phosphate
Structure-Activity Relationship
Triazoles / chemistry*
Triazoles / pharmacology

Substances

Amides
Dipeptidyl-Peptidase IV Inhibitors
Piperazines
Protease Inhibitors
Pyrazines
Triazoles
Sitagliptin Phosphate