Structural highlights
Publication Abstract from PubMed
We report herein the discovery of novel integrase-LEDGF/p75 allosteric inhibitors (INLAIs) based on a benzene scaffold 3. This scaffold can extend substituents from the C1 position unlike the common pyridine scaffolds 2. Structure-activity relationship studies showed that the sulfonamide linker at the C1 position was important for the antiviral activity. Interaction between sulfonamide and Q95 was observed by X-ray crystallography. Compound 31h showed more potent antiviral activity (EC50 (NL432) = 3.9 nM) than BI-224436 (EC50 (NL432) = 56 nM), suggesting the potential of the newly designed scaffold 3.
Discovery of novel integrase-LEDGF/p75 allosteric inhibitors based on a benzene scaffold.,Sugiyama S, Iwaki T, Tamura Y, Tomita K, Matsuoka E, Arita S, Seki T, Yoshinaga T, Kawasuji T Bioorg Med Chem. 2020 Sep 1;28(17):115643. doi: 10.1016/j.bmc.2020.115643. Epub, 2020 Jul 10. PMID:32773094[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sugiyama S, Iwaki T, Tamura Y, Tomita K, Matsuoka E, Arita S, Seki T, Yoshinaga T, Kawasuji T. Discovery of novel integrase-LEDGF/p75 allosteric inhibitors based on a benzene scaffold. Bioorg Med Chem. 2020 Sep 1;28(17):115643. PMID:32773094 doi:10.1016/j.bmc.2020.115643
