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PubMed · 15188220

New antithrombotics with an indazole structure.

Ali Kemal Yildiz·Klaus Rehse·Johannes-Peter Stasch·Erwin Bischoff
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Abstract

Fifteen new indazole derivatives have been synthesized. In the Born test, compounds (4f) and (4g) were most active. They inhibited the blood platelet aggregation induced by collagen with an IC(50) = 85 or 90 microM, respectively. After oral administration to rats (60 mg/kg) three of the compounds significantly inhibited the formation of thrombi in arterioles and venules. The strongest effect was observed with (4j) which showed an inhibition of 15% in arterioles and 7% in venules. Further experiments showed that compound (4j) does not mediate these effects by activating soluble guanylate cyclase, but likely by inhibiting phosphodiesterase isoform PDE 5.

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3',5'-Cyclic-GMP PhosphodiesterasesAnimalsCyclic Nucleotide Phosphodiesterases, Type 5Enzyme ActivationFibrinolytic AgentsGuanylate CyclaseHumansIn Vitro TechniquesIndazolesPhosphodiesterase InhibitorsPhosphoric Diester HydrolasesPlatelet AggregationPlatelet Aggregation InhibitorsRatsThrombosisComparative StudyJournal Article

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Ali Kemal Yildiz, Klaus Rehse, Johannes-Peter Stasch, Erwin Bischoff. 2004. New antithrombotics with an indazole structure.. https://doi.org/10.1002/ardp.200300832

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