Arylazoamidoximes and related compounds as NO-modulators.

Three amidinoarylhydrazines 1, three arylazoamidines 2, and nine arylazoamidoximes 3 have been synthesized and investigated for their potential to function as nitric oxide (NO) modulators. In-vitro studies demonstrated that 2 and 3 inhibited platelet aggregation (2c, IC(50 )= 3 microM) which could also be shown in vivo by inhibition of thrombus formation in arterioles (3a, 22%). Moreover, for all compounds antihypertensive effects were examined in vivo with SHR rats, with 2a being the most potent candidate by lowering blood pressure by 19%.

New 1H-pyrazole-4-carboxamides with antiplatelet activity.

Nine title compounds were synthesized and investigated in the Born test for their antiplatelet activities against collagen, ADP, adrenaline, and platelet activating factor (PAF) as inducers of the aggregation. Using collagen three compounds with IC50 values below 100 microM were found (3b, 3e, 3i). Activities in nanomolar concentrations were observed against ADP (3b, IC50 = 9.

New 2-amino-thiazole-4-acetamides with antiplatelet activity.

In the Born test, 23 title compounds were synthesized and investigated for their antiplatelet activities against collagen, ADP, adrenaline, and platelet-activating factor (PAF) as inducers of the aggregation. Using collagen, three compounds with IC(50) values below 10 microM were found (3a, 3b, 3c) and 15 compounds with IC(50) values between 10 and 100 microM were determined. In general, a cyclohexylamino rest on an 4-carboxamide moiety is a pre-requisite for this pharmacological activity.

New purines with antiplatelet activity.

Four purine-2,6-diamines, 4a, b, 5a, b, nineteen N-(purin-2-yl)benzenecarboxamides 6a-q, 7b, and one N-(purin-2-yl)-2-furanecarboxamide 8 were prepared for the first time and tested for their inhibition of blood platelet aggregation. Six compounds, 6a, b, h, m, o, p, inhibited the platelet aggregation induced by collagen with IC(50 )values between 3 and 10 micromol/L in the Born test. ADP, PAF, and adrenaline were used as specific aggregation inducers to examine the mechanism of the anti-aggregating activity.

New pyrimido[5,4-c]cinnolines with antiplatelet activities.

Twenty one new pyrimido[5,4-c]cinnolines containing different lipophilic moieties (viz. phenyl, 4-methoxyphenyl, 2-furanyl, 2-thienyl) in position 2 and additional basic groups (e.g.