Discovery of new chemotype dipeptidyl peptidase IV inhibitors having (R)-3-amino-3-methyl piperidine as a pharmacophore

Yukihiro Nishio; Hidenori Kimura; Shinya Tosaki; Eiji Sugaru; Mutsuko Sakai; Masakuni Horiguchi; Yumi Masui; Michiko Ono; Tsutomu Nakagawa; Hiroyuki Nakahira

doi:10.1016/j.bmcl.2010.10.101

Discovery of new chemotype dipeptidyl peptidase IV inhibitors having (R)-3-amino-3-methyl piperidine as a pharmacophore

Bioorg Med Chem Lett. 2010 Dec 15;20(24):7246-9. doi: 10.1016/j.bmcl.2010.10.101. Epub 2010 Oct 26.

Authors

Yukihiro Nishio¹, Hidenori Kimura, Shinya Tosaki, Eiji Sugaru, Mutsuko Sakai, Masakuni Horiguchi, Yumi Masui, Michiko Ono, Tsutomu Nakagawa, Hiroyuki Nakahira

Affiliation

¹ Drug Research Division, Dainippon Sumitomo Pharma Co., Ltd, Konohana-ku, Osaka, Japan. yukihiro-nishio@ds-pharma.co.jp

PMID: 21074430
DOI: 10.1016/j.bmcl.2010.10.101

Abstract

Structures containing the (R)-3-amino-3-methyl piperidine unit as a new pharmacophore moiety have been shown to possess moderate inhibitory activity for DPP-4 with good pharmacokinetics profile. One of these compounds was found to have good oral bioavailability and PK/PD profile in ZF-rat.

MeSH terms

Animals
Dipeptidyl Peptidase 4 / chemistry*
Dipeptidyl Peptidase 4 / metabolism
Dipeptidyl-Peptidase IV Inhibitors / chemical synthesis
Dipeptidyl-Peptidase IV Inhibitors / chemistry*
Dipeptidyl-Peptidase IV Inhibitors / pharmacokinetics
Drug Evaluation, Preclinical
Humans
Microsomes, Liver / metabolism
Piperidines / chemical synthesis
Piperidines / chemistry*
Piperidines / pharmacokinetics
Pyrimidinones / chemical synthesis
Pyrimidinones / chemistry*
Pyrimidinones / pharmacokinetics
Rats
Stereoisomerism
Structure-Activity Relationship

Substances

(R)-3-amino-3-methylpiperidine
Dipeptidyl-Peptidase IV Inhibitors
Piperidines
Pyrimidinones
Dipeptidyl Peptidase 4