开发和推广用于潜在治疗精神分裂症的肌卡因乙酰胆碱受体激动剂 KTX-005 的有利合成路线

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2025-02-05 DOI:10.1021/acs.oprd.4c00531

Hanchao Zheng, Rui Zhang, Michel Leeman, Christopher R. H. Hale, Giorgio Attardo, Vijaya B. Gondi

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Development and Scale-Up of an Enabling Synthetic Route to KTX-005, a Muscarinic Acetylcholine Receptor Agonist for the Potential Treatment of Schizophrenia

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Development and Scale-Up of an Enabling Synthetic Route to KTX-005, a Muscarinic Acetylcholine Receptor Agonist for the Potential Treatment of Schizophrenia

Development and optimization of phase-appropriate synthetic technologies to prepare KTX-005, a potent muscarinic acetylcholine receptor agonist, are described in this article. The modular strategy involves three building blocks: commercially available materials dichlorothiadiazole (21), butanethiol (22), and custom-synthesized azabicyclo derivative (18). The highlight of the enabling synthetic strategy toward KTX-005 is a unique thiadiazole ring opening/closing sequence to facilitate both dichlorothiadiazole desymmetrization with butanethiol as well as functionalization of the azabicyclo ring derivative 18.

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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.