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Updated: Jul 12, 2026

Synthesis of pH Dependent Pyrazole, Imidazole, and Isoindolone Dipyrrinone Fluorophores using a Claisen-Schmidt Condensation Approach
Published on: June 10, 2021
Structure-activity studies on diphenylpyrazine derivatives: a novel class of prostacyclin receptor agonists
Tetsuo Asaki1, Taisuke Hamamoto, Yukiteru Sugiyama
1Discovery Research Laboratories, Nippon Shinyaku Co Ltd, Kisshoin, Kyoto, Japan. t.asaki@po.nippon-shinyaku.co.jp
Abstract:
To develop nonprostanoid prostacyclin receptor agonists with a high degree of metabolic resistance and an extended duration of action, a novel series of diphenylpyrazine derivatives was synthesized and evaluated for their inhibition of ADP-induced human platelet aggregation. Structure-activity relationship studies on the side chain containing the carboxylic acid moiety of the lead compound 5c showed that the length of the linker and the presence of the concatenating nitrogen atom adjacent to the pyrazine ring are critical for the antiaggregatory activity. This study led to the discovery of 2-amino-5,6-diphenylpyrazine derivatives 8c, 15a, and 15b, which showed potent inhibition of platelet aggregation with IC(50) values of 0.2 microM. Among these compounds, 15b is an orally available and long-lasting prostacyclin receptor agonist which is promising for the treatment of various vascular diseases.
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