Syntheses and medicinal chemistry of spiro heterocyclic steroids

IF 2.2 4区 化学 Q2 CHEMISTRY, ORGANIC Beilstein Journal of Organic Chemistry Pub Date : 2024-07-24 DOI:10.3762/bjoc.20.152
Laura L. Romero-Hernández, Ana Isabel Ahuja-Casarín, Penélope Merino-Montiel, Sara Montiel-Smith, José Luis Vega-Báez, Jesús Sandoval-Ramírez
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Abstract

There is compelling evidence that incorporating a heterocyclic moiety into a steroid can alter its pharmacological and pharmacokinetic properties, driving intense interest in the synthesis of such hybrids among research groups. In this review, we present an overview of recent synthetic methodologies, spanning the period from 2000 to 2023, for the preparation of spiro heterocyclic steroids. The compounds surveyed encompass four-, five-, six-, and seven-membered heterocycles appended to various positions of steroidal backbones, with spirocycles containing oxygen, nitrogen, and sulfur atoms being predominant. The outlined synthetic procedures emphasize the pivotal steps for constructing the heterocycles, often accompanied by a detailed account of the overall synthesis pathway. The review encompasses innovative compounds, including bis-steroids linked by a spiro heterocycle and steroids conjugated to heterocyclic moieties containing three or more (hetero)cycles. Moreover, many compounds are accompanied by data on their biological activities, such as antiproliferative, antimalarial, antimicrobial, antifungal, steroid antagonist, and enzyme inhibition, among others, aimed at furnishing pertinent insights for the future design of more potent and selective drugs.

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Beilstein J. Org. Chem. 2024, 20, 1713–1745. doi:10.3762/bjoc.20.152

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螺环杂环类固醇的合成与药物化学
摘要有令人信服的证据表明,在类固醇中加入杂环分子可改变其药理和药代动力学特性,从而激发了研究小组对合成此类杂环分子的浓厚兴趣。在本综述中,我们概述了从 2000 年到 2023 年期间制备螺环杂环类固醇的最新合成方法。所调查的化合物包括固醇骨架不同位置上的四元、五元、六元和七元杂环,其中以含有氧、氮和硫原子的螺环为主。概述的合成程序强调了构建杂环的关键步骤,通常还附有整个合成途径的详细说明。综述涵盖了创新化合物,包括由螺杂环连接的双类固醇,以及与含有三个或三个以上(杂)环的杂环分子共轭的类固醇。此外,许多化合物还附有关于其生物活性的数据,如抗增殖、抗疟、抗菌、抗真菌、类固醇拮抗剂和酶抑制等,旨在为今后设计更有效和更具选择性的药物提供相关见解。Chem.2024, 20, 1713–1745. doi:10.3762/bjoc.20.152
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来源期刊
CiteScore
4.90
自引率
3.70%
发文量
167
审稿时长
1.4 months
期刊介绍: The Beilstein Journal of Organic Chemistry is an international, peer-reviewed, Open Access journal. It provides a unique platform for rapid publication without any charges (free for author and reader) – Platinum Open Access. The content is freely accessible 365 days a year to any user worldwide. Articles are available online immediately upon publication and are publicly archived in all major repositories. In addition, it provides a platform for publishing thematic issues (theme-based collections of articles) on topical issues in organic chemistry. The journal publishes high quality research and reviews in all areas of organic chemistry, including organic synthesis, organic reactions, natural product chemistry, structural investigations, supramolecular chemistry and chemical biology.
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