7d83

Crystal structure of HIV-1 integrase catalytic core domain in complex with 2-(tert-butoxy)-2-(2-(3-cyclohexylureido)-3,6-dimethyl-5-(5-methylchroman-6-yl)pyridin-4-yl)acetic acidCrystal structure of HIV-1 integrase catalytic core domain in complex with 2-(tert-butoxy)-2-(2-(3-cyclohexylureido)-3,6-dimethyl-5-(5-methylchroman-6-yl)pyridin-4-yl)acetic acid

Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.43Å Ligands: , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed We have discovered HIV-1 novel integrase-LEDGF/p75 allosteric inhibitors (INLAIs) based on a pyridine scaffold forming an intramolecular hydrogen bond. Scaffolds containing a pyridine moiety have been studied extensively and we have already reported that substituents extending from the C1 position contributed to the antiviral potency. In this study, we designed a new pyridine scaffold 2 with a substituent at the C1 position. Interestingly, during attempts at optimization, we found that the direction of the C1 substituents with an intramolecular hydrogen bond contributed to the antiviral potency. Compound 34f exhibited better antiviral potency against WT and the T174I mutant (EC50 (WT) = 6.6 nM, EC50 (T174I) = 270 nM) than BI 224436 (EC50 (WT) = 22 nM, EC50 (T174I) > 5000 nM). Discovery of novel HIV-1 integrase-LEDGF/p75 allosteric inhibitors based on a pyridine scaffold forming an intramolecular hydrogen bond.,Sugiyama S, Akiyama T, Taoda Y, Iwaki T, Matsuoka E, Akihisa E, Seki T, Yoshinaga T, Kawasuji T Bioorg Med Chem Lett. 2020 Dec 11;33:127742. doi: 10.1016/j.bmcl.2020.127742. PMID:33316407 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Retroviral integrase 3D structures

spinqualitylabelsall models 7d83, resolution 2.43Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image