Recent Progress in the Discovery and Development of 2-Nitroimidazooxazines and 6-Nitroimidazooxazoles to Treat Tuberculosis and Neglected Tropical Diseases
Nitroimidazole drugs have a long history as therapeutic agents to treat bacterial and parasitic diseases. The discovery in 1989 of a bicyclic nitroimidazole lead, displaying in vitro and in vivo antitubercular activity, spurred intensive exploration of this and related scaffolds, which led to the re...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-09-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/18/4137 |
| _version_ | 1797554049966407680 |
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| author | Hollis D. Showalter |
| author_facet | Hollis D. Showalter |
| author_sort | Hollis D. Showalter |
| collection | DOAJ |
| description | Nitroimidazole drugs have a long history as therapeutic agents to treat bacterial and parasitic diseases. The discovery in 1989 of a bicyclic nitroimidazole lead, displaying in vitro and in vivo antitubercular activity, spurred intensive exploration of this and related scaffolds, which led to the regulatory approval of pretomanid and delamanid as a new class of tuberculosis drugs. Much of the discovery work related to this took place over a 20-year period ending in 2010, which is covered in a number of cited reviews. This review highlights subsequent research published over the 2011–August 2020 timeframe, and captures detailed structure–activity relationship studies and synthetic strategies directed towards uncovering newer generation drugs for both tuberculosis and selected neglected tropical diseases. Additionally, this review presents in silico calculations relating to the drug-like properties of lead compounds and clinical agents, as well as chemical development and manufacturing processes toward providing bulk drug supplies. |
| first_indexed | 2024-03-10T16:25:16Z |
| format | Article |
| id | doaj.art-32d9c96ba26c42f3a72c264ff38df19a |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T16:25:16Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-32d9c96ba26c42f3a72c264ff38df19a2023-11-20T13:14:09ZengMDPI AGMolecules1420-30492020-09-012518413710.3390/molecules25184137Recent Progress in the Discovery and Development of 2-Nitroimidazooxazines and 6-Nitroimidazooxazoles to Treat Tuberculosis and Neglected Tropical DiseasesHollis D. Showalter0Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USANitroimidazole drugs have a long history as therapeutic agents to treat bacterial and parasitic diseases. The discovery in 1989 of a bicyclic nitroimidazole lead, displaying in vitro and in vivo antitubercular activity, spurred intensive exploration of this and related scaffolds, which led to the regulatory approval of pretomanid and delamanid as a new class of tuberculosis drugs. Much of the discovery work related to this took place over a 20-year period ending in 2010, which is covered in a number of cited reviews. This review highlights subsequent research published over the 2011–August 2020 timeframe, and captures detailed structure–activity relationship studies and synthetic strategies directed towards uncovering newer generation drugs for both tuberculosis and selected neglected tropical diseases. Additionally, this review presents in silico calculations relating to the drug-like properties of lead compounds and clinical agents, as well as chemical development and manufacturing processes toward providing bulk drug supplies.https://www.mdpi.com/1420-3049/25/18/4137tuberculosisneglected tropical diseasespretomaniddelamanid2-nitroimidazooxazines6-nitroimidazooxazoles |
| spellingShingle | Hollis D. Showalter Recent Progress in the Discovery and Development of 2-Nitroimidazooxazines and 6-Nitroimidazooxazoles to Treat Tuberculosis and Neglected Tropical Diseases Molecules tuberculosis neglected tropical diseases pretomanid delamanid 2-nitroimidazooxazines 6-nitroimidazooxazoles |
| title | Recent Progress in the Discovery and Development of 2-Nitroimidazooxazines and 6-Nitroimidazooxazoles to Treat Tuberculosis and Neglected Tropical Diseases |
| title_full | Recent Progress in the Discovery and Development of 2-Nitroimidazooxazines and 6-Nitroimidazooxazoles to Treat Tuberculosis and Neglected Tropical Diseases |
| title_fullStr | Recent Progress in the Discovery and Development of 2-Nitroimidazooxazines and 6-Nitroimidazooxazoles to Treat Tuberculosis and Neglected Tropical Diseases |
| title_full_unstemmed | Recent Progress in the Discovery and Development of 2-Nitroimidazooxazines and 6-Nitroimidazooxazoles to Treat Tuberculosis and Neglected Tropical Diseases |
| title_short | Recent Progress in the Discovery and Development of 2-Nitroimidazooxazines and 6-Nitroimidazooxazoles to Treat Tuberculosis and Neglected Tropical Diseases |
| title_sort | recent progress in the discovery and development of 2 nitroimidazooxazines and 6 nitroimidazooxazoles to treat tuberculosis and neglected tropical diseases |
| topic | tuberculosis neglected tropical diseases pretomanid delamanid 2-nitroimidazooxazines 6-nitroimidazooxazoles |
| url | https://www.mdpi.com/1420-3049/25/18/4137 |
| work_keys_str_mv | AT hollisdshowalter recentprogressinthediscoveryanddevelopmentof2nitroimidazooxazinesand6nitroimidazooxazolestotreattuberculosisandneglectedtropicaldiseases |