Division of Pharmaceutical Chemistry, Faculty of Pharmacy, Babu Banarasi Das Northern India Institute of Technology, Lucknow 226028, UP, India.
Pharmacy Department, Banasthali Vidyapith, Banasthali, Tonk 304022, Rajasthan, India.
Eur J Med Chem. 2018 Feb 10;145:445-497. doi: 10.1016/j.ejmech.2018.01.003. Epub 2018 Jan 4.
This review aims to be a comprehensive, authoritative, critical, and readable review of general interest to the medicinal chemistry community because it focuses on the pharmacological, chemical, structural and computational aspects of diverse chemical categories as monoamine oxidase inhibitors (MAOIs). Monoamine oxidases (MAOs), namely MAO-A and MAO-B represent an enormously valuable class of neuronal enzymes embodying neurobiological origin and functions, serving as potential therapeutic target in neuronal pharmacotherapy, and hence we have coined the term "Neurozymes" which is being introduced for the first time ever. Nowadays, therapeutic attention on MAOIs engrosses two imperative categories; MAO-A inhibitors, in certain mental disorders such as depression and anxiety, and MAO-B inhibitors, in neurodegenerative disorders like Alzheimer's disease (AD) and Parkinson's disease (PD). The use of MAOIs declined due to some potential side effects, food and drug interactions, and introduction of other classes of drugs. However, curiosity in MAOIs is reviving and the recent developments of new generation of highly selective and reversible MAOIs, have renewed the therapeutic prospective of these compounds. The initial section of the review emphasizes on the detailed classification, structural and binding characteristics, therapeutic potential, current status and future challenges of the privileged pharmacophores. However, the chemical prospective of privileged scaffolds such as; aliphatic and aromatic amines, amides, hydrazines, azoles, diazoles, tetrazoles, indoles, azines, diazines, xanthenes, tricyclics, benzopyrones, and more interestingly natural products, along with their conclusive SARs have been discussed in the later segment of review. The last segment of the article encompasses some patents granted in the field of MAOIs, in a simplistic way.
这篇综述旨在全面、权威、批判性地综述单胺氧化酶抑制剂 (MAOIs) 作为一类具有广泛兴趣的药物化学领域，因为它侧重于药理学、化学、结构和计算方面的各种化学类别。单胺氧化酶 (MAOs)，即 MAO-A 和 MAO-B，代表了一类非常有价值的神经元酶，具有神经生物学起源和功能，作为神经元药物治疗的潜在治疗靶点，因此我们创造了“Neurozymes”一词，这是首次引入。如今，MAOIs 的治疗关注集中在两个重要类别上；MAO-A 抑制剂，在某些精神疾病如抑郁症和焦虑症中，以及 MAO-B 抑制剂，在神经退行性疾病如阿尔茨海默病 (AD) 和帕金森病 (PD) 中。由于一些潜在的副作用、食物和药物相互作用以及其他类别的药物的引入，MAOIs 的使用有所减少。然而，对 MAOIs 的兴趣正在恢复，新一代高度选择性和可逆 MAOIs 的最新发展，为这些化合物的治疗前景带来了新的活力。综述的初始部分强调了特权药效团的详细分类、结构和结合特征、治疗潜力、现状和未来挑战。然而，特权支架的化学前景，如脂肪族和芳香族胺、酰胺、肼、唑、二唑、四唑、吲哚、嗪、二嗪、呫吨、三环、苯并吡喃酮，更有趣的是天然产物，以及它们的结论性 SARs，在综述的后一部分进行了讨论。文章的最后一部分以简单的方式涵盖了 MAOIs 领域授予的一些专利。
