A series of biheterocyclic assemblies comprising of 1,2,5-oxadiazole and azasydnone scaffolds were synthesized and biologically evaluated as novel nitric oxide (NO)-donor and antiplatelet agents. Depending on functional substituents at the biheterocyclic core, all studied compounds demonstrated good NO-donor profiles releasing NO in a wide range of concentrations (19.2%–195.1%) according to a Griess assay. (1,2,5-Oxadiazolyl)azasydnones showed excellent antiplatelet activity in the case of ADP and adrenaline used as inducers completely suppressing the aggregate formation even at the lowest test concentration of 0.0375 μmol/ml, which is a rather unique feature. Moreover, studied biheterocycles possess a selective mechanism of inhibition of platelet aggregation mediated only by ADP and adrenaline, which are considered to be the main inducers causing thrombus formation. In addition, (1,2,5-oxadiazolyl)azasydnones were found to be completely non-toxic to hybrid endothelial cells EaHy 926. Studies of hydrolytic degradation of the synthesized compounds afforded benzoic acid as a sole detectable decomposition product, which is considered advantageous in drug design. Therefore, (1,2,5-oxadiazolyl)azasydnones represent a novel class of promising drug candidates with improved antiplatelet profile and reduced toxicity enabling their huge potential in medicinal chemistry and drug design.

中文翻译：

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(1,2,5-恶二唑基)azasydnone 环组件作为新型抗血小板药物的抗凝集作用

合成了一系列由 1,2,5-恶二唑和氮杂环酮支架组成的双杂环组件，并将其作为新型一氧化氮 (NO) 供体和抗血小板药物进行了生物学评估。根据双杂环核心​​的功能取代基，所有研究的化合物都表现出良好的 NO 供体特征，根据 Griess 测定，在广泛的浓度范围内 (19.2%–195.1%) 释放 NO。(1,2,5-Oxadiazolyl)azasydnones 在 ADP 和肾上腺素用作诱导剂的情况下显示出优异的抗血小板活性，即使在 0.0375 μmol/ml 的最低测试浓度下也完全抑制聚集体形成，这是一个相当独特的特征。此外，研究的双杂环具有选择性抑制血小板聚集的机制，仅由 ADP 和肾上腺素介导，被认为是导致血栓形成的主要诱因。此外，(1,2,5-恶二唑基)azasydnones 被发现对混合内皮细胞 EaHy 926 完全无毒。对合成化合物的水解降解的研究提供了苯甲酸作为唯一可检测的分解产物，这被认为是有利的在药物设计中。因此，(1,2,5-恶二唑基)azasydnones 代表了一类新的有前途的候选药物，具有改善的抗血小板特性和降低的毒性，使其在药物化学和药物设计中具有巨大的潜力。这在药物设计中被认为是有利的。因此，(1,2,5-恶二唑基)azasydnones 代表了一类新的有前途的候选药物，具有改善的抗血小板特性和降低的毒性，使其在药物化学和药物设计中具有巨大的潜力。这在药物设计中被认为是有利的。因此，(1,2,5-恶二唑基)azasydnones 代表了一类新的有前途的候选药物，具有改善的抗血小板特性和降低的毒性，使其在药物化学和药物设计中具有巨大的潜力。