Abstract：
Azepanes or azepines are structural motifs of many drugs, drug candidates and evaluated lead compounds. Even though compounds having N-heterocyclic 7-membered rings are often found in nature (e.g. alkaloids), the natural compounds of this group are rather rare as approved therapeutics. Thus, recently studied and approved azepane or azepine-congeners predominantly consist of semi-synthetically or synthetically-obtained scaffolds. In this review a comparison of approved drugs and recently investigated leads was proposed taking into regard their structural aspects (stereochemistry), biological activities, pharmacokinetic properties and confirmed molecular targets. The 7-membered N-heterocycles reveal a wide range of biological activities, not only against CNS diseases, but also as e.g. antibacterial, anticancer, antiviral, antiparasitic and against allergy agents. As most of the approved or investigated potential drugs or lead structures, belonging to 7-membered N-heterocycles, are synthetic scaffolds, this report also reveals different and efficient metal-free cascade approaches useful to synthesize both simple azepane or azepine-containing congeners and those of oligocyclic structures. Stereochemistry of azepane/azepine fused systems, in view of biological data and binding with the targets, is discussed. Apart from the approved drugs, we compare advances in SAR studies of 7-membered N-heterocycles (mainly from 2018 to 2023), whereas the related synthetic part concerning various domino strategies is focused on the last ten years.
摘要：
氮杂环丁烷或氮卓类是许多药物的结构基序，候选药物和评估的先导化合物。即使在自然界中经常发现具有N-杂环7元环的化合物（例如生物碱），这一组的天然化合物是相当罕见的批准的治疗。因此，最近研究和批准的氮杂环庚烷或氮杂环庚烷-同源物主要由半合成或合成获得的支架组成。在这篇综述中，考虑到它们的结构方面（立体化学），提出了批准的药物和最近研究的线索的比较。生物活动，药代动力学特性和确认的分子靶标。7元N-杂环揭示了广泛的生物活性，不仅针对中枢神经系统疾病，但也如抗菌，抗癌，抗病毒，抗寄生虫和抗过敏剂。作为大多数批准或研究的潜在药物或铅结构，属于7元N-杂环，是合成支架，该报告还揭示了不同的，有效的无金属级联方法，可用于合成简单的氮杂环庚烷或含氮杂环的同类物以及具有寡环结构的同类物。氮杂环庚烷/氮杂融合系统的立体化学，鉴于生物学数据和与靶标的结合，正在讨论。除了批准的药物，我们比较了7元N-杂环的SAR研究进展(主要是2018年至2023年)，而关于各种多米诺骨牌策略的相关合成部分集中在最近十年。
