Structural highlights
Publication Abstract from PubMed
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.
Design, synthesis, and X-ray studies of potent HIV-1 protease inhibitors incorporating aminothiochromane and aminotetrahydronaphthalene carboxamide derivatives as the P2 ligands.,Ghosh AK, Jadhav RD, Simpson H, Kovela S, Osswald H, Agniswamy J, Wang YF, Hattori SI, Weber IT, Mitsuya H Eur J Med Chem. 2018 Sep 18;160:171-182. doi: 10.1016/j.ejmech.2018.09.046. PMID:30340140[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ghosh AK, Jadhav RD, Simpson H, Kovela S, Osswald H, Agniswamy J, Wang YF, Hattori SI, Weber IT, Mitsuya H. Design, synthesis, and X-ray studies of potent HIV-1 protease inhibitors incorporating aminothiochromane and aminotetrahydronaphthalene carboxamide derivatives as the P2 ligands. Eur J Med Chem. 2018 Sep 18;160:171-182. doi: 10.1016/j.ejmech.2018.09.046. PMID:30340140 doi:http://dx.doi.org/10.1016/j.ejmech.2018.09.046
