| Autor: |
Derun Li, Hongjun Zhang, Hua Zhou, Xuelei Song, Theodore A. Martinot, Prasanthi Geda, Brett A. Hopkins, Jeanine E. Ballard, Stella H. Vincent, Yongxin Han, Nicolas Solban, Karin M. Otte, Mangeng Cheng, J. Richard Miller, Qinglin Pu, Indu Bharathan, Charles A. Lesburg, Ryan D. Cohen, Ian Knemeyer, David Jonathan Bennett, Xavier Fradera, Alfred Lammens, Nadya Smotrov |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
ACS Med Chem Lett |
| ISSN: |
1948-5875 |
| Popis: |
[Image: see text] Herein the discovery of potent IDO1 inhibitors with low predicted human dose is discussed. Metabolite identification (MetID) and structural data were used to strategically incorporate cyclopropane rings into this tetrahydronaphthyridine series of IDO1 inhibitors to improve their metabolic stability and potency. Enabling synthetic chemistry was developed to construct these unique fused cyclopropyl compounds, leading to inhibitors with improved pharmacokinetics and human whole blood potency and a predicted human oral dose as low as 9 mg once daily (QD). |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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