Fluoropyrrolidine amides as dipeptidyl peptidase IV inhibitors

Charles G Caldwell; Ping Chen; Jiafang He; Emma R Parmee; Barbara Leiting; Frank Marsilio; Reshma A Patel; Joseph K Wu; George J Eiermann; Aleksandr Petrov; Huaibing He; Kathryn A Lyons; Nancy A Thornberry; Ann E Weber

doi:10.1016/j.bmcl.2003.12.040

Fluoropyrrolidine amides as dipeptidyl peptidase IV inhibitors

Bioorg Med Chem Lett. 2004 Mar 8;14(5):1265-8. doi: 10.1016/j.bmcl.2003.12.040.

Authors

Charles G Caldwell¹, Ping Chen, Jiafang He, Emma R Parmee, Barbara Leiting, Frank Marsilio, Reshma A Patel, Joseph K Wu, George J Eiermann, Aleksandr Petrov, 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. [email protected]

PMID: 14980678
DOI: 10.1016/j.bmcl.2003.12.040

Abstract

Amides derived from fluorinated pyrrolidines and 4-substituted cyclohexylglycine analogues have been prepared and evaluated as inhibitors of dipeptidyl dipeptidase IV (DP-IV). Analogues which incorporated (S)-3-fluoropyrrolidine showed good selectivity for DP-IV over quiescent cell proline dipeptidase (QPP). Compound 48 had good pharmacokinetic properties and was orally active in an oral glucose tolerance test in lean mice.

Publication types

Comparative Study

MeSH terms

Adenosine Deaminase / metabolism
Adenosine Deaminase Inhibitors*
Amides / chemistry*
Amides / pharmacology
Animals
Dogs
Fluorine / chemistry
Fluorine / pharmacology
Glycoproteins / antagonists & inhibitors*
Glycoproteins / metabolism
Isoenzymes / antagonists & inhibitors
Isoenzymes / metabolism
Mice
Mice, Inbred C57BL
Protease Inhibitors / chemistry*
Protease Inhibitors / pharmacology
Pyrrolidines / chemistry*
Pyrrolidines / pharmacology
Rats

Substances

Adenosine Deaminase Inhibitors
Amides
Glycoproteins
Isoenzymes
Protease Inhibitors
Pyrrolidines
Fluorine
Adenosine Deaminase