Abstract：
Carbon dioxide (CO2) is an economically viable and abundant carbon source that can be incorporated into compounds such as 1,3-azoles relevant to the pharmaceutical, cosmetics, and pesticide industries. Of the 2.4 million commercially available C2-unsubstituted 1,3-azole compounds, less than 1 % are currently purchasable as their C2-carboxylated derivatives, highlighting the substantial gap in compound availability. This availability gap leaves ample opportunities for exploring the synthetic accessibility and use of carboxylated azoles in bioactive compounds. In this study, we analyze and quantify the relevance of C2-carboxylated 1,3-azoles in small-molecule research. An analysis of molecular databases such as ZINC, ChEMBL, COSMOS, and DrugBank identified relevant C2-carboxylated 1,3-azoles as anticoagulant and aroma-giving compounds. Moreover, a pharmacophore analysis highlights promising pharmaceutical potential associated with C2-carboxylated 1,3-azoles, revealing the ATP-sensitive inward rectifier potassium channel 1 (KATP) and Kinesin-like protein KIF18A as targets that can potentially be addressed with C2-carboxylated 1,3-azoles. Moreover, we identified several bioisosteres of C2-carboxylated 1,3-azoles. In conclusion, further exploration of the chemical space of C2-carboxylated 1,3-azoles is encouraged to harness their full potential in drug discovery and related fields.
摘要：
二氧化碳（CO2）是一种经济上可行且丰富的碳源，可以掺入到与药物相关的化合物如1,3-唑中。化妆品,和农药工业。在240万种市售C2-未取代的1,3-唑化合物中，目前可购买的C2-羧化衍生物不到1%，突出了化合物可用性的巨大差距。这种可用性差距为探索生物活性化合物中羧化唑的合成可及性和用途留下了充足的机会。在这项研究中,我们分析和量化小分子研究中C2-羧化1,3-唑的相关性。对ZINC等分子数据库的分析，ChEMBL,COSMOS,和DrugBank确定相关的C2-羧化1,3-唑作为抗凝剂和芳香化合物。此外，药效分析强调了与C2-羧化1,3-唑相关的有前途的药物潜力，揭示了ATP敏感的内向整流钾通道1（KATP）和驱动蛋白样蛋白KIF18A作为靶标，可以用C2-羧化的1,3-唑类药物解决。此外，我们鉴定了几种C2-羧化1,3-唑的生物等排物。总之,鼓励进一步探索C2-羧化1,3-唑的化学空间，以利用它们在药物发现和相关领域的全部潜力。
