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.

Synthesis and antiplatelet activity of new imidazole-4-carboxylic acid derivatives.

1-Arylalkyl-5-phenylsulfonamino-imidazole-4-carboxylic acid esters and their carboxamides with an additional secondary amino group were synthesized and identified as antiplatelet agents in a low micromolar range (Born-test, inducer collagen). To describe the mechanism of action more precisely the Born-test was carried out as well with ADP, adrenaline or PAF, respectively. In addition, two compounds were investigated for their COX-1 inhibitory activities.

New oxadiazole derivatives showing partly antiplatelet, antithrombotic and serotonin antagonistic properties.

Ten new 1, 2, 4-oxadiazole- and six new 1, 3, 4-oxadiazole-carboxamides containing different lipophilic moieties (i.e. 4-biphenyl-, 1-naphthyl, phenylpropyl- and n-hexyl substituents) and additional basic groups which are mainly alkyl- and dialkylaminoalkyl residues have been synthesized and tested for antiplatelet effects in vitro (Born-test) and antithrombotic properties in vivo (laser thrombosis model).

New antithrombotics with an indazole structure.

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.

Antiaggregating and antithrombotic activities of new 1, 2, 3-triazolecarboxamides.

Twenty five new triazolecarboxamides related to YC-1 were prepared and tested for their antiplatelet (in vitro) and antithrombotic (in vivo) activities. Five of them inhibited the aggregation of blood platelets (Born test, inducer collagen) with IC50 values between 90 and 130 microM. Nine compounds exhibited significant antithrombotic properties with an inhibition of thrombus formation between 11 and 7%.

New antithrombotic 1-phthalazinamines with serotonin antagonistic properties.

We report nineteen 4-aryl- and 4-arylalkyl-1-phthalazinamines (5-8) which we prepared and tested for antithrombotic properties. All compounds were assayed for their antiplatelet activity in the "Born test" with collagen as inducer of the aggregation. N-[4-(1H-1, 2, 4-triazol-1-yl)butyl]-4-phenyl-1-phthalazin-amine (7 c) was the most potent compound, having an IC(50) of 8 microM.