AI Article Synopsis
- Fifteen new indazole derivatives were synthesized, with compounds (4f) and (4g) showing the highest activity in inhibiting collagen-induced blood platelet aggregation (IC(50) = 85 or 90 µM).
- Oral administration of these compounds to rats (60 mg/kg) resulted in a significant reduction in thrombus formation in arterioles and venules, with compound (4j) showing the most substantial effects (15% in arterioles, 7% in venules).
- Further studies indicated that compound (4j) likely exerts its effects by inhibiting phosphodiesterase isoform PDE 5, rather than activating soluble guanylate cyclase.
Article 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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| http://dx.doi.org/10.1002/ardp.200300832 | DOI Listing |
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