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 acid

7D83 の概要

• エントリーDOI: 10.2210/pdb7d83/pdb
• 分子名称: Integrase, SULFATE ION, (2S)-2-[2-(cyclohexylcarbamoylamino)-3,6-dimethyl-5-(5-methyl-3,4-dihydro-2H-chromen-6-yl)pyridin-4-yl]-2-[(2-methylpropan-2-yl)oxy]ethanoic acid, ... (4 entities in total)
• 機能のキーワード: hiv-1 integrase, viral protein
• 由来する生物種: Human immunodeficiency virus type 1 group M subtype B (isolate NY5) (HIV-1)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 19246.58

構造登録者

Sugiyama, S.,Sekiguchi, Y. (登録日: 2020-10-07, 公開日: 2021-01-13, 最終更新日: 2024-10-23)

主引用文献

Sugiyama, S.,Akiyama, T.,Taoda, Y.,Iwaki, T.,Matsuoka, E.,Akihisa, E.,Seki, T.,Yoshinaga, T.,Kawasuji, T.
Discovery of novel HIV-1 integrase-LEDGF/p75 allosteric inhibitors based on a pyridine scaffold forming an intramolecular hydrogen bond.
Bioorg.Med.Chem.Lett., 33:127742-127742, 2020

PubMed Abstract: 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 (EC (WT) = 6.6 nM, EC (T174I) = 270 nM) than BI 224436 (EC (WT) = 22 nM, EC (T174I) > 5000 nM).

PubMed: 33316407
DOI: 10.1016/j.bmcl.2020.127742

実験手法

X-RAY DIFFRACTION (2.43 Å)