Synthesis and Biological Activities of 4-Phenyl-5-pyridyl-1,3-thiazole Derivatives as Selective Adenosine A3 Antagonists

Seiji Miwatashi; Yasuyoshi Arikawa; Tatsumi Matsumoto; Keiko Uga; Naoyuki Kanzaki; Yumi N. Imai; Shigenori Ohkawa

doi:10.1248/cpb.56.1126

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Synthesis and Biological Activities of 4-Phenyl-5-pyridyl-1,3-thiazole Derivatives as Selective Adenosine A₃ Antagonists

Seiji Miwatashi, Yasuyoshi Arikawa, Tatsumi Matsumoto, Keiko Uga, Naoyuki Kanzaki, Yumi N. Imai, Shigenori Ohkawa

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Keywords: 5-pyridyl-1,3-thiazole, adenosine A₃ receptor antagonist, antiphlogistic, rat antigen-induced asthma model, Brown Norway rat

JOURNAL FREE ACCESS

2008 Volume 56 Issue 8 Pages 1126-1137

DOI https://doi.org/10.1248/cpb.56.1126

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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, A_2A 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.

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