Design, synthesis, and biological evaluation of triazolopiperazine-based beta-amino amides as potent, orally active dipeptidyl peptidase IV (DPP-4) inhibitors

Jennifer E Kowalchick; Barbara Leiting; KellyAnn D Pryor; Frank Marsilio; Joseph K Wu; Huaibing He; Kathryn A Lyons; George J Eiermann; Aleksandr Petrov; Giovanna Scapin; Reshma A Patel; Nancy A Thornberry; Ann E Weber; Dooseop Kim

doi:10.1016/j.bmcl.2007.07.100

Design, synthesis, and biological evaluation of triazolopiperazine-based beta-amino amides as potent, orally active dipeptidyl peptidase IV (DPP-4) inhibitors

Bioorg Med Chem Lett. 2007 Nov 1;17(21):5934-9. doi: 10.1016/j.bmcl.2007.07.100. Epub 2007 Aug 23.

Authors

Jennifer E Kowalchick¹, Barbara Leiting, KellyAnn D Pryor, Frank Marsilio, Joseph K Wu, Huaibing He, Kathryn A Lyons, George J Eiermann, Aleksandr Petrov, Giovanna Scapin, Reshma A Patel, Nancy A Thornberry, Ann E Weber, Dooseop Kim

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. [email protected]

PMID: 17827003
DOI: 10.1016/j.bmcl.2007.07.100

Abstract

Various beta-amino amides containing triazolopiperazine heterocycles have been prepared and evaluated as potent, selective, orally active dipeptidyl peptidase IV (DPP-4) inhibitors. These compounds display excellent oral bioavailability and good overall pharmacokinetic profiles in preclinical species. Moreover, in vivo efficacy in an oral glucose tolerance test in lean mice is demonstrated.

MeSH terms

Amides / chemical synthesis
Amides / chemistry*
Amides / pharmacokinetics
Amides / pharmacology*
Animals
Crystallography, X-Ray
Dipeptidyl-Peptidase IV Inhibitors*
Drug Design
Drug Evaluation, Preclinical
Models, Molecular
Piperazines / chemistry*
Protease Inhibitors / chemical synthesis
Protease Inhibitors / chemistry*
Protease Inhibitors / pharmacokinetics
Protease Inhibitors / pharmacology*
Rats

Substances

Amides
Dipeptidyl-Peptidase IV Inhibitors
Piperazines
Protease Inhibitors