Discovery, SAR, and X-ray structure of novel biaryl-based dipeptidyl peptidase IV inhibitors

Lei Qiao; Christian A Baumann; Carl S Crysler; Nisha S Ninan; Marta C Abad; John C Spurlino; Renee L Desjarlais; Jukka Kervinen; Mike P Neeper; Shariff S Bayoumy; Robyn Williams; Ingrid C Deckman; Malini Dasgupta; Rolanda L Reed; Norman D Huebert; Bruce E Tomczuk; Kevin J Moriarty

doi:10.1016/j.bmcl.2005.09.037

Discovery, SAR, and X-ray structure of novel biaryl-based dipeptidyl peptidase IV inhibitors

Bioorg Med Chem Lett. 2006 Jan 1;16(1):123-8. doi: 10.1016/j.bmcl.2005.09.037. Epub 2005 Oct 19.

Authors

Lei Qiao¹, Christian A Baumann, Carl S Crysler, Nisha S Ninan, Marta C Abad, John C Spurlino, Renee L Desjarlais, Jukka Kervinen, Mike P Neeper, Shariff S Bayoumy, Robyn Williams, Ingrid C Deckman, Malini Dasgupta, Rolanda L Reed, Norman D Huebert, Bruce E Tomczuk, Kevin J Moriarty

Affiliation

¹ Johnson and Johnson Pharmaceutical Research and Development, 665 Stockton Drive, Exton, PA 19341, USA.

PMID: 16236500
DOI: 10.1016/j.bmcl.2005.09.037

Abstract

The discovery, SAR, and X-ray crystal structure of novel biarylaminoacyl-(S)-2-cyano-pyrrolidines and biarylaminoacylthiazolidines as potent inhibitors of dipeptidyl peptidase IV (DPP IV) are reported.

MeSH terms

Animals
Antineoplastic Agents / pharmacology
Binding Sites
Blood Glucose / metabolism
Caco-2 Cells
Chemistry, Pharmaceutical / methods*
Crystallography, X-Ray / methods*
Dipeptidyl Peptidase 4 / chemistry*
Dipeptidyl Peptidase 4 / metabolism
Drug Design
Drug Screening Assays, Antitumor
Enzyme Inhibitors / pharmacology*
Humans
Kinetics
Mice
Models, Chemical
Models, Molecular
Protease Inhibitors / pharmacology*
Rats
Structure-Activity Relationship

Substances

Antineoplastic Agents
Blood Glucose
Enzyme Inhibitors
Protease Inhibitors
Dipeptidyl Peptidase 4