Substituted piperidinyl glycinyl 2-cyano-4,5-methano pyrrolidines as potent and stable dipeptidyl peptidase IV inhibitors

Guohua Zhao; Chet Kwon; Aiying Wang; James G Robertson; Jovita Marcinkeviciene; Rex A Parker; Mark S Kirby; Lawrence G Hamann

doi:10.1016/j.bmcl.2013.01.104

Substituted piperidinyl glycinyl 2-cyano-4,5-methano pyrrolidines as potent and stable dipeptidyl peptidase IV inhibitors

Bioorg Med Chem Lett. 2013 Mar 15;23(6):1622-5. doi: 10.1016/j.bmcl.2013.01.104. Epub 2013 Jan 31.

Authors

Guohua Zhao¹, Chet Kwon, Aiying Wang, James G Robertson, Jovita Marcinkeviciene, Rex A Parker, Mark S Kirby, Lawrence G Hamann

Affiliation

¹ Bristol-Myers Squibb Research and Development, PO Box 5400, Princeton, NJ 08543-5400, USA. [email protected]

PMID: 23416006
DOI: 10.1016/j.bmcl.2013.01.104

Abstract

Synthesis and structure-activity relationship of a series of substituted piperidinyl glycine 2-cyano-4,5-methano pyrroline DPP-IV inhibitors are described. Improvement of the inhibitory activity and chemical stability of this series of compounds was respectively achieved by the introduction of bulky groups at the 4-position and 1-position of the piperidinyl glycine, leading to a series of potent and stable DPP-IV inhibitors.

MeSH terms

Dipeptidyl Peptidase 4 / chemistry*
Dipeptidyl Peptidase 4 / metabolism
Dipeptidyl-Peptidase IV Inhibitors / chemical synthesis
Dipeptidyl-Peptidase IV Inhibitors / chemistry*
Dipeptidyl-Peptidase IV Inhibitors / metabolism
Humans
Hydrogen-Ion Concentration
Piperidines / chemistry*
Protein Binding
Pyrrolidines / chemical synthesis
Pyrrolidines / chemistry*
Pyrrolidines / metabolism
Structure-Activity Relationship
Temperature

Substances

Dipeptidyl-Peptidase IV Inhibitors
Piperidines
Pyrrolidines
piperidine
Dipeptidyl Peptidase 4