Continuous Flow Enabled Synthesis of Multiresistant Drug Clofazimine

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED Organic Process Research & Development Pub Date : 2024-11-01 DOI:10.1021/acs.oprd.4c0042010.1021/acs.oprd.4c00420

Rajat Pandey, Faith Akwi and Paul Watts*,

引用次数: 0

Abstract

Drug resistance to tuberculosis is still one of the major challenges worldwide. Clofazimine, which belongs to the riminophenazine (antibiotic) class, is still one of the active drugs that are efficient against drug-resistant Mycobacterium tuberculosis. Apart from this, it is also a WHO-approved drug for the treatment of leprosy and, at present, is under phase 2 clinical trial for its activity against the SARS-CoV-2 virus. Owing to its vast importance in clinical research, we have developed a semicontinuous flow-mediated synthesis of Clofazimine using readily available p-chloroaniline and 1-fluoro-2-nitrobenzene. The target drug molecule was obtained from four consecutive chemical transformations with nominal residence time, improved purity, and yields when compared to the batch process. Moreover, the first two steps were also successfully telescoped under the optimized reaction conditions.

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多耐药性药物氯法齐明的连续流合成

结核病的耐药性仍然是全球面临的主要挑战之一。氯法齐明属于利米诺吩嗪（抗生素）类，目前仍是有效抗耐药结核分枝杆菌的药物之一。此外，它还是世界卫生组织批准用于治疗麻风病的药物，目前正在进行第二阶段临床试验，以研究它对 SARS-CoV-2 病毒的活性。鉴于氯噻嗪在临床研究中的重要作用，我们利用容易获得的对氯苯胺和 1-氟-2-硝基苯，开发了一种半连续流介导的氯噻嗪合成方法。与间歇工艺相比，通过四次连续的化学转化获得了目标药物分子，停留时间更短，纯度和产率均有所提高。此外，在优化的反应条件下，前两个步骤也成功实现了伸缩。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Organic Process Research & Development 化学-应用化学

CiteScore

6.90

自引率

14.70%

发文量

251

审稿时长

2 months

期刊介绍： The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools，process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.

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