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Development of the Enabling Route for Glecaprevir via Ring-Closing Metathesis
Glecaprevir was identified as a potent HCV NS3/4A protease inhibitor, and an enabling synthesis was required to support the preclinical evaluation and subsequent Phase I clinical trials. The enabling route to glecaprevir was established through further development of the medicinal chemistry route. T...
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| Published in: | Organic process research & development 2020-02, Vol.24 (2), p.183-200 |
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| Main Authors: | , , , , , , , , , , , , , , , , , , |
| Format: | Article |
| Language: | English |
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| cited_by | cdi_FETCH-LOGICAL-a280t-b86038a237bcd158c48df331798031e75304838d25ddc1be6b8d25c3405632873 |
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| cites | cdi_FETCH-LOGICAL-a280t-b86038a237bcd158c48df331798031e75304838d25ddc1be6b8d25c3405632873 |
| container_end_page | 200 |
| container_issue | 2 |
| container_start_page | 183 |
| container_title | Organic process research & development |
| container_volume | 24 |
| creator | Cink, Russell D Lukin, Kirill A Bishop, Richard D Zhao, Gang Pelc, Matthew J Towne, Timothy B Gates, Bradley D Ravn, Matthew M Hill, David R Ding, Chen Cullen, Steven C Mei, Jianzhang Leanna, M. Robert Henle, Jeremy Napolitano, José G Nere, Nandkishor K Chen, Shuang Sheikh, Ahmad Kallemeyn, Jeffrey M |
| description | Glecaprevir was identified as a potent HCV NS3/4A protease inhibitor, and an enabling synthesis was required to support the preclinical evaluation and subsequent Phase I clinical trials. The enabling route to glecaprevir was established through further development of the medicinal chemistry route. The key steps in the synthesis involved a ring-closing metathesis (RCM) reaction to form the 18-membered macrocycle and a challenging fluorination step to form a key amino acid. The enabling route was successfully used to produce 41 kg of glecaprevir, sufficient to support the preclinical evaluation and early clinical development. |
| doi_str_mv | 10.1021/acs.oprd.9b00469 |
| format | article |
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| source | American Chemical Society:Jisc Collections:American Chemical Society Read & Publish Agreement 2022-2024 (Reading list) |
| title | Development of the Enabling Route for Glecaprevir via Ring-Closing Metathesis |
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