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吡啶和二氢吡啶支架在药物设计中的作用不断扩大。

The Expanding Role of Pyridine and Dihydropyridine Scaffolds in Drug Design.

机构信息

Department of Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People's Republic of China.

School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, Henan, People's Republic of China.

出版信息

Drug Des Devel Ther. 2021 Oct 13;15:4289-4338. doi: 10.2147/DDDT.S329547. eCollection 2021.

Abstract

Pyridine-based ring systems are one of the most extensively used heterocycles in the field of drug design, primarily due to their profound effect on pharmacological activity, which has led to the discovery of numerous broad-spectrum therapeutic agents. In the US FDA database, there are 95 approved pharmaceuticals that stem from pyridine or dihydropyridine, including isoniazid and ethionamide (tuberculosis), delavirdine (HIV/AIDS), abiraterone acetate (prostate cancer), tacrine (Alzheimer's), ciclopirox (ringworm and athlete's foot), crizotinib (cancer), nifedipine (Raynaud's syndrome and premature birth), piroxicam (NSAID for arthritis), nilvadipine (hypertension), roflumilast (COPD), pyridostigmine (myasthenia gravis), and many more. Their remarkable therapeutic applications have encouraged researchers to prepare a larger number of biologically active compounds decorated with pyridine or dihydropyridine, expandeing the scope of finding a cure for other ailments. It is thus anticipated that myriad new pharmaceuticals containing the two heterocycles will be available in the forthcoming decade. This review examines the prospects of highly potent bioactive molecules to emphasize the advantages of using pyridine and dihydropyridine in drug design. We cover the most recent developments from 2010 to date, highlighting the ever-expanding role of both scaffolds in the field of medicinal chemistry and drug development.

摘要

吡啶基环系是药物设计领域中应用最广泛的杂环之一,主要是因为它们对药理学活性有深远的影响,这导致了许多广谱治疗剂的发现。在美国 FDA 数据库中,有 95 种已批准的药物源自吡啶或二氢吡啶,包括异烟肼和乙胺丁醇(结核病)、德拉韦啶(HIV/AIDS)、阿比特龙醋酸盐(前列腺癌)、他克林(阿尔茨海默病)、环吡酮(癣和脚气)、克唑替尼(癌症)、硝苯地平(雷诺氏综合征和早产)、吡罗昔康(关节炎的 NSAID)、尼伐地平(高血压)、罗氟司特(COPD)、吡啶斯的明(重症肌无力)等等。它们显著的治疗应用鼓励研究人员制备更多具有吡啶或二氢吡啶结构的生物活性化合物,扩大了寻找其他疾病治疗方法的范围。因此,预计在未来十年内将有大量含有这两种杂环的新型药物问世。本文综述了具有高潜力的生物活性分子的前景,强调了在药物设计中使用吡啶和二氢吡啶的优势。我们涵盖了 2010 年至今的最新发展,突出了这两个支架在药物化学和药物开发领域中的作用不断扩大。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cba1/8520849/5674dc39cc52/DDDT-15-4289-g0001.jpg

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