title: Synthesis and structure-activity relationship of 4-amino-2-phenylpyrimidine derivatives as a series of novel GPR119 agonists.
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.
authors.affiliation: Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. kenji.negoro@astellas.com
authors.forename: Kenji
authors.initials: K
authors.lastname: Negoro
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yonetoku
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Maruyama
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yoshida
authors.forename: Makoto
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Ohta
mesh_terms: D000284:Administration, Oral; D000818:Animals; D003497:Cyclic N-Oxides / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C554427:2-(4-bromophenyl)-6-methyl-N-(2-(1-oxidopyridin-3-yl)ethyl)pyrimidin-4-amine; D003497:Cyclic N-Oxides; C519854:GPR119 protein, human; D011725:Pyridines; D011743:Pyrimidines; D043562:Receptors, G-Protein-Coupled; C030986:pyrimidine