title: Synthesis and biological activity of novel alpha-substituted beta-phenylpropionic acids having pyridin-2-ylphenyl moiety as antihyperglycemic agents.
abstract: We previously reported the identification of novel oximes having 5-benzyl-2,4-thiazolidinedione with antihyperglycemic activity. We now report the synthesis and biological activity of a novel series of oximes and amides having alpha-substituted-beta-phenylpropionic acids. In this series, we obtained potent PPAR alpha/gamma dual agonist (S)-9d, with which activation of PPAR alpha and PPAR gamma was considerably more potent than that of the reference compounds GW9578 22 and rosiglitazone 3, respectively. This means (S)-9d is of the strongest class of PPAR alpha/gamma dual agonists. In the course of this study, we also obtained 8h, which indicated potent plasma glucose lowering effect in spite of weak PPAR alpha/gamma agonistic activity.
authors.affiliation: Medicinal Chemistry Research Laboratories, Sankyo Co., Ltd., Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. takamu@shina.sankyo.co.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Takamura
authors.forename: Mitsuya
authors.initials: M
authors.lastname: Sakurai
authors.forename: Eriko
authors.initials: E
authors.lastname: Yamada
authors.forename: Sachie
authors.initials: S
authors.lastname: Fujita
authors.forename: Makoto
authors.initials: M
authors.lastname: Yachi
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takagi
authors.forename: Aya
authors.initials: A
authors.lastname: Isobe
authors.forename: Yuka
authors.initials: Y
authors.lastname: Hagisawa
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yanagisawa
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists; D010666:Phenylpropionates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013057:Spectrum Analysis
chemical_list: D017931:DNA Primers; D007004:Hypoglycemic Agents; D047492:Peroxisome Proliferator-Activated Receptors; D010666:Phenylpropionates; D011725:Pyridines; C035253:3-phenylpropionic acid