Practical and Efficient Synthesis of 2‑Thio-imidazole DerivativeZY12201: A Potent TGR5 Agonist
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...
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| Veröffentlicht in: | Organic process research & development 2020-08, Vol.24 (8), p.1508-1514 |
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| creator | Joshi, Vivek M Sojitra, Chandrakant Sasane, Santosh Shukla, Mrigendra Chauhan, Rakesh Chaubey, Vipin Jain, Sarika Shah, Kalpesh Mande, Hemant Soman, Shubhangi Pamidimukkala, Padmaja Sudhakar Shah, Shailesh R Pandey, Bipin Singh, Kumar K Agarwal, Sameer |
| description | 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. |
| doi_str_mv | 10.1021/acs.oprd.0c00234 |
| format | Article |
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Process Res. Dev</addtitle><date>2020-08-21</date><risdate>2020</risdate><volume>24</volume><issue>8</issue><spage>1508</spage><epage>1514</epage><pages>1508-1514</pages><issn>1083-6160</issn><eissn>1520-586X</eissn><abstract>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. 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| title | Practical and Efficient Synthesis of 2‑Thio-imidazole DerivativeZY12201: A Potent TGR5 Agonist |
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