Synthesis and structure-activity relationship of 4-amino-2-phenylpyrimidine derivatives as a series of novel GPR119 agonists

Kenji Negoro; Yasuhiro Yonetoku; Tatsuya Maruyama; Shigeru Yoshida; Makoto Takeuchi; Mitsuaki Ohta

doi:10.1016/j.bmc.2012.02.006

Synthesis and structure-activity relationship of 4-amino-2-phenylpyrimidine derivatives as a series of novel GPR119 agonists

Bioorg Med Chem. 2012 Apr 1;20(7):2369-75. doi: 10.1016/j.bmc.2012.02.006. Epub 2012 Feb 10.

Authors

Kenji Negoro¹, Yasuhiro Yonetoku, Tatsuya Maruyama, Shigeru Yoshida, Makoto Takeuchi, Mitsuaki Ohta

Affiliation

¹ Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. kenji.negoro@astellas.com

PMID: 22365911
DOI: 10.1016/j.bmc.2012.02.006

Abstract

Through preparation and examination of a series of novel 4-amino-2-phenylpyrimidine derivatives as agonists for GPR119, we identified 2-(4-bromophenyl)-6-methyl-N-[2-(1-oxidopyridin-3-yl)ethyl]pyrimidin-4-amine (9t). Compound 9t improved glucose tolerance in mice following oral administration and showed good pharmacokinetic profiles in rats.

Published by Elsevier Ltd.

MeSH terms

Administration, Oral
Animals
Cyclic N-Oxides / chemical synthesis*
Cyclic N-Oxides / chemistry
Cyclic N-Oxides / pharmacokinetics
HEK293 Cells
Humans
Male
Mice
Mice, Inbred ICR
Pyridines / chemical synthesis*
Pyridines / chemistry
Pyridines / pharmacokinetics
Pyrimidines / chemical synthesis
Pyrimidines / chemistry*
Pyrimidines / pharmacokinetics
Rats
Receptors, G-Protein-Coupled / agonists*
Receptors, G-Protein-Coupled / metabolism
Structure-Activity Relationship

Substances

2-(4-bromophenyl)-6-methyl-N-(2-(1-oxidopyridin-3-yl)ethyl)pyrimidin-4-amine
Cyclic N-Oxides
GPR119 protein, human
Pyridines
Pyrimidines
Receptors, G-Protein-Coupled
pyrimidine