在过去的60年中,嘧啶已成为许多药物分子中越来越重要的核心结构。本文调查了嘧啶在药物发现疗法中产生重大影响的最新领域,包括抗感染药,抗癌,免疫学,免疫肿瘤学,神经系统疾病,慢性疼痛,和糖尿病。本文介绍了药物的合成,并强调了生物靶标在疾病模型中的作用。此外,生物效力,讨论了ADME特性和药代动力学/药效学(如果有)。这项调查试图证明嘧啶类药物的多功能性,不仅因为它们的效力和亲和力,而且还因为嘧啶作为苯基和其他芳香族π系统的生物等排体的改善的药物化学性质。希望本文将为考虑嘧啶支架作为未来候选药物的化学型的研究人员提供见解,以抵消以前认为无法治疗的医疗状况。
Pyrimidines have become an increasingly important core structure in many drug molecules over the past 60 years. This article surveys recent areas in which pyrimidines have had a major impact in drug discovery therapeutics, including anti-infectives, anticancer, immunology, immuno-oncology, neurological disorders, chronic pain, and diabetes mellitus. The article presents the synthesis of the medicinal agents and highlights the role of the biological target with respect to the disease model. Additionally, the biological potency, ADME properties and pharmacokinetics/pharmacodynamics (if available) are discussed. This survey attempts to demonstrate the versatility of pyrimidine-based drugs, not only for their potency and affinity but also for the improved medicinal chemistry properties of pyrimidine as a bioisostere for phenyl and other aromatic π systems. It is hoped that this article will provide insight to researchers considering the pyrimidine scaffold as a chemotype in future drug candidates in order to counteract medical conditions previously deemed untreatable.