Substituted piperazines as novel dipeptidyl peptidase IV inhibitors

Linda L Brockunier; Jiafang He; Lawrence F Colwell Jr; Bahanu Habulihaz; Huaibing He; Barbara Leiting; Kathryn A Lyons; Frank Marsilio; Reshma A Patel; Yohannes Teffera; Joseph K Wu; Nancy A Thornberry; Ann E Weber; Emma R Parmee

doi:10.1016/j.bmcl.2004.06.065

Substituted piperazines as novel dipeptidyl peptidase IV inhibitors

Bioorg Med Chem Lett. 2004 Sep 20;14(18):4763-6. doi: 10.1016/j.bmcl.2004.06.065.

Authors

Linda L Brockunier¹, Jiafang He, Lawrence F Colwell Jr, Bahanu Habulihaz, Huaibing He, Barbara Leiting, Kathryn A Lyons, Frank Marsilio, Reshma A Patel, Yohannes Teffera, Joseph K Wu, Nancy A Thornberry, Ann E Weber, Emma R Parmee

Affiliation

¹ Department of Medicinal Chemistry, Merck & Co. Inc., PO Box 2000, Rahway, NJ 07065, USA. [email protected]

PMID: 15324904
DOI: 10.1016/j.bmcl.2004.06.065

Abstract

Incorporation of a fluorophenyl beta-amino amide moiety into piperazine screening lead 2 has resulted in the discovery of a structurally novel series of potent and selective DP-IV inhibitors. Simplification of the molecule and incorporation of multiple fluorine atoms on the phenyl ring has provided low molecular weight analogs such as compound 32, which is a 19nM DP-IV inhibitor with >4000-fold selectivity over QPP.

Publication types

Comparative Study

MeSH terms

Administration, Oral
Animals
Biological Availability
Dipeptidyl Peptidase 4 / metabolism*
Half-Life
In Vitro Techniques
Male
Microsomes, Liver / metabolism
Piperazines / chemical synthesis
Piperazines / chemistry
Piperazines / pharmacology*
Protease Inhibitors / chemical synthesis
Protease Inhibitors / chemistry
Protease Inhibitors / pharmacology*
Rats
Rats, Sprague-Dawley
Stereoisomerism
Structure-Activity Relationship

Substances

Piperazines
Protease Inhibitors
Dipeptidyl Peptidase 4