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作为 P2X7 受体拮抗剂的合成分子:专注于治疗炎症性疾病的药物化学更新。

Synthetic molecules as P2X7 receptor antagonists: A medicinal chemistry update focusing the therapy of inflammatory diseases.

机构信息

Laboratório de Síntese de Fármacos (LASFAR) - Farmanguinhos - Fiocruz Brazil; Instituto Federal do Rio de Janeiro - IFRJ, Rio de Janeiro, Brazil.

Laboratório de Síntese de Fármacos (LASFAR) - Farmanguinhos - Fiocruz Brazil.

出版信息

Eur J Pharmacol. 2023 Oct 15;957:175999. doi: 10.1016/j.ejphar.2023.175999. Epub 2023 Aug 22.

DOI:10.1016/j.ejphar.2023.175999
PMID:37619787
Abstract

Stimulation of the P2X7 receptor by extracellular adenosine 5'-triphosphate induces a series of responses in the organism, exceptionally protein cascades related to the proinflammatory process. This has made P2X7 a target for research on inflammatory diseases such as rheumatoid arthritis. Thus, the incessant search for new prototypes that aim to antagonize the action of P2X7 has been remarkable in recent decades, a factor that has already led to numerous clinical studies in humans. In this review, we present the key molecules developed over the years with potential inhibition of P2X7 and inflammation. In addition, an update with newly developed chemical classes with promising activity and results in clinical studies for human pathologies focusing on P2X7 inhibition.

摘要

细胞外三磷酸腺苷对 P2X7 受体的刺激会在体内引起一系列反应,特别是与炎症过程相关的蛋白级联反应。这使得 P2X7 成为研究类风湿性关节炎等炎症性疾病的靶点。因此,近几十年来,人们一直在不懈地寻找新的原型药物,以拮抗 P2X7 的作用,这一因素已经导致了大量针对人类的临床研究。在这篇综述中,我们介绍了多年来开发的具有潜在 P2X7 抑制和抗炎作用的关键分子。此外,还更新了一些新开发的化学类别,这些类别在针对 P2X7 抑制的人类病理的临床研究中具有有前景的活性和结果。

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