title: Synthesis and biological activities of 4-phenyl-5-pyridyl-1,3-thiazole derivatives as selective adenosine A3 antagonists.
abstract: To investigate the potency of an adenosine A3 receptor (A3AR) antagonist as an anti-asthmatic drug, a novel series of 4-phenyl-5-pyridyl-1,3-thiazole derivatives was synthesized and evaluated in human adenosine A1, A2A and A3 receptor and rat adenosine A3 receptor binding assays. From investigation of the SAR study, compound 7af was identified as a highly potent human and rat A3AR antagonist. This compound inhibited IB-MECA-induced plasma protein extravasation in the skin of rats and showed good oral absorption. Also, compound 7af significantly inhibited antigen-induced hyper-responsiveness to acetylcholine in actively sensitized Brown Norway rats. These results show that 4-phenyl-5-pyridyl-1,3-thiazole derivatives are potential candidates to enable the evaluation of A3AR antagonists. Further evaluation of this class of compounds may afford a novel anti-inflammatory agent such as an anti-asthmatic drug.
authors.affiliation: Pharmaceutical Research Division, Takeda Pharmaceutical Company, Ltd, Osaka, Japan. Miwatashi_Seiji@takeda.co.jp
authors.forename: Seiji
authors.initials: S
authors.lastname: Miwatashi
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Arikawa
authors.forename: Tatsumi
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Keiko
authors.initials: K
authors.lastname: Uga
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kanzaki
authors.forename: Yumi N
authors.initials: YN
authors.lastname: Imai
authors.forename: Shigenori
authors.initials: S
authors.lastname: Ohkawa
mesh_terms: D058918:Adenosine A3 Receptor Antagonists; D000818:Animals; D006801:Humans; D051381:Rats; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D058918:Adenosine A3 Receptor Antagonists; D013844:Thiazoles