Practical and Efficient Synthesis of 2-Thio-imidazole Derivative—ZY12201: A Potent TGR5 Agonist,Organic Process Research & Development

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Practical and Efficient Synthesis of 2-Thio-imidazole Derivative—ZY12201: A Potent TGR5 Agonist
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2020-07-30 , DOI: 10.1021/acs.oprd.0c00234
Vivek M. Joshi _{1,

2} , Chandrakant Sojitra _{1,

2,

3} , Santosh Sasane _{1,

2} , Mrigendra Shukla ₁ , Rakesh Chauhan ₁ , Vipin Chaubey ₁ , Sarika Jain ₁ , Kalpesh Shah ₁ , Hemant Mande ₂ , Shubhangi Soman ₂ , Padmaja Sudhakar Pamidimukkala ₂ , Shailesh R. Shah ₂ , Bipin Pandey ₁ , Kumar K. Singh ₃ , Sameer Agarwal ₁

Affiliation

Early scalable process development for the synthesis of ZY12201, a novel TGR5 receptor agonist, as a potential clinical candidate is described. A practical, efficient, and scalable synthetic route provided ZY12201 in seven steps and 32% overall yield. The key step involves an inexpensive acetic acid-mediated cyclization of thiourea 6 for the construction of 2-thio-imidazole derivative 7. The developed process demonstrated cost-effective, high-yielding, kilogram-scalable, and environmentally friendly synthesis of ZY12201. This high-yielding route enabled us to rapidly synthesize large quantities of ZY12201 in 99% purity to support in vivo and toxicity studies.

中文翻译：

高效实用的2-硫代咪唑衍生物ZY12201的合成：强效TGR5激动剂

描述了用于潜在的临床候选物ZY12201（一种新型TGR5受体激动剂）的合成的早期可扩展方法开发。一条实用，高效且可扩展的合成路线以七个步骤提供了ZY12201，总产率为32％。关键步骤涉及廉价的乙酸介导的硫脲6的环化反应，以构建2-硫代咪唑衍生物7。所开发的工艺证明了ZY12201具有成本效益，高产量，可缩放规模且环保的特点。这种高产途径使我们能够快速合成大量纯度为99％的ZY12201，以支持体内和毒性研究。

更新日期：2020-08-21

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