| Structural highlights
Publication Abstract from PubMed
Design, synthesis, and evaluation of a new class of HIV-1 protease inhibitors containing diverse flexible macrocyclic P1'-P2' tethers are reported. Inhibitor 5a with a pyrrolidinone-derived macrocycle exhibited favorable enzyme inhibitory and antiviral activity (Ki=13.2nM, IC50=22nM). Further incorporation of heteroatoms in the macrocyclic skeleton provided macrocyclic inhibitors 5m and 5o. These compounds showed excellent HIV-1 protease inhibitory (Ki=62pM and 14pM, respectively) and antiviral activity (IC50=5.3nM and 2.0nM, respectively). Inhibitor 5o also remained highly potent against a DRV-resistant HIV-1 variant.
Design, synthesis, X-ray studies, and biological evaluation of novel macrocyclic HIV-1 protease inhibitors involving the P1'-P2' ligands.,Ghosh AK, Sean Fyvie W, Brindisi M, Steffey M, Agniswamy J, Wang YF, Aoki M, Amano M, Weber IT, Mitsuya H Bioorg Med Chem Lett. 2017 Sep 6. pii: S0960-894X(17)30892-2. doi:, 10.1016/j.bmcl.2017.09.003. PMID:28958624[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ghosh AK, Sean Fyvie W, Brindisi M, Steffey M, Agniswamy J, Wang YF, Aoki M, Amano M, Weber IT, Mitsuya H. Design, synthesis, X-ray studies, and biological evaluation of novel macrocyclic HIV-1 protease inhibitors involving the P1'-P2' ligands. Bioorg Med Chem Lett. 2017 Sep 6. pii: S0960-894X(17)30892-2. doi:, 10.1016/j.bmcl.2017.09.003. PMID:28958624 doi:http://dx.doi.org/10.1016/j.bmcl.2017.09.003
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