Design, synthesis, and X-ray studies of potent HIV-1 protease inhibitors incorporating aminothiochromane and aminotetrahydronaphthalene carboxamide derivatives as the P2 ligands
Abstract
We describe the design, synthesis, and biological evaluation of a series of novel HIV-1 protease inhibitors with carboxamide derivatives as the P2 ligands. We have specifically designed aminothiochromane and aminotetrahydronaphthalene-based carboxamide ligands to promote hydrogen bonding and van der Waals interactions in the active site of HIV-1 protease. Inhibitors 4e and 4j have shown potent enzyme inhibitory and antiviral activity. High resolution X-ray crystal structures of 4d- and 4k-bound HIV-1 protease revealed molecular insights into the ligand-binding site interactions.
- Authors:
-
[1];
- Purdue Univ., West Lafayette, IN (United States)
- Georgia State Univ., Atlanta, GA (United States)
- National Center for Global Health & Medicine Research Inst., Tokyo (Japan)
- National Center for Global Health & Medicine Research Inst., Tokyo (Japan); Kumamoto University Graduate School of Medical and Pharmaceutical Sciences (Japan); National Inst. of Health (NIH), Bethesda, MD (United States)
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC); National Inst. of Health
- OSTI Identifier:
- 1482242
- Grant/Contract Number:
- GM53386; GM62920
- Resource Type:
- Accepted Manuscript
- Journal Name:
- European Journal of Medicinal Chemistry
- Additional Journal Information:
- Journal Volume: 160; Journal Issue: C; Journal ID: ISSN 0223-5234
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; HIV-1 protease inhibitors; P2 ligand; drug resistance; design and synthesis; X-ray crystal structure
Citation Formats
Ghosh, Arun K., Jadhav, Ravindra D., Simpson, Hannah, Kovela, Satish, Osswald, Heather, Agniswamy, Johnson, Wang, Yuan-Fang, Hattori, Shin-ichiro, Weber, Irene T., and Mitsuya, Hiroaki. Design, synthesis, and X-ray studies of potent HIV-1 protease inhibitors incorporating aminothiochromane and aminotetrahydronaphthalene carboxamide derivatives as the P2 ligands. United States: N. p., 2018.
Web. doi:10.1016/j.ejmech.2018.09.046.
Ghosh, Arun K., Jadhav, Ravindra D., Simpson, Hannah, Kovela, Satish, Osswald, Heather, Agniswamy, Johnson, Wang, Yuan-Fang, Hattori, Shin-ichiro, Weber, Irene T., & Mitsuya, Hiroaki. Design, synthesis, and X-ray studies of potent HIV-1 protease inhibitors incorporating aminothiochromane and aminotetrahydronaphthalene carboxamide derivatives as the P2 ligands. United States. https://doi.org/10.1016/j.ejmech.2018.09.046
Ghosh, Arun K., Jadhav, Ravindra D., Simpson, Hannah, Kovela, Satish, Osswald, Heather, Agniswamy, Johnson, Wang, Yuan-Fang, Hattori, Shin-ichiro, Weber, Irene T., and Mitsuya, Hiroaki. Tue .
"Design, synthesis, and X-ray studies of potent HIV-1 protease inhibitors incorporating aminothiochromane and aminotetrahydronaphthalene carboxamide derivatives as the P2 ligands". United States. https://doi.org/10.1016/j.ejmech.2018.09.046. https://www.osti.gov/servlets/purl/1482242.
@article{osti_1482242,
title = {Design, synthesis, and X-ray studies of potent HIV-1 protease inhibitors incorporating aminothiochromane and aminotetrahydronaphthalene carboxamide derivatives as the P2 ligands},
author = {Ghosh, Arun K. and Jadhav, Ravindra D. and Simpson, Hannah and Kovela, Satish and Osswald, Heather and Agniswamy, Johnson and Wang, Yuan-Fang and Hattori, Shin-ichiro and Weber, Irene T. and Mitsuya, Hiroaki},
abstractNote = {We describe the design, synthesis, and biological evaluation of a series of novel HIV-1 protease inhibitors with carboxamide derivatives as the P2 ligands. We have specifically designed aminothiochromane and aminotetrahydronaphthalene-based carboxamide ligands to promote hydrogen bonding and van der Waals interactions in the active site of HIV-1 protease. Inhibitors 4e and 4j have shown potent enzyme inhibitory and antiviral activity. High resolution X-ray crystal structures of 4d- and 4k-bound HIV-1 protease revealed molecular insights into the ligand-binding site interactions.},
doi = {10.1016/j.ejmech.2018.09.046},
journal = {European Journal of Medicinal Chemistry},
number = C,
volume = 160,
place = {United States},
year = {Tue Sep 18 00:00:00 EDT 2018},
month = {Tue Sep 18 00:00:00 EDT 2018}
}
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