2CEJ

P1' Extended HIV-1 Protease Inhibitors Encompassing a Tertiary Alcohol in the Transition-State Mimicking Scaffold

2CEJ の概要

• エントリーDOI: 10.2210/pdb2cej/pdb
• 関連するPDBエントリー: 1WBK 1WBM 2CEM 2CEN
• 分子名称: POL PROTEIN, 3-AMINO-3-BENZYL-[4.3.0]BICYCLO-1,6-DIAZANONAN-2-ONE (3 entities in total)
• 機能のキーワード: hiv-1, protease, inhibitor, aspartyl protease, hydrolase
• 由来する生物種: HUMAN IMMUNODEFICIENCY VIRUS 1
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22289.13

構造登録者

Ginman, N.,Ekegren, J.K.,Johansson, A.,Wallberg, H.,Larhed, M.,Samuelsson, B.,Hallberg, A.,Unge, T. (登録日: 2006-02-07, 公開日: 2007-02-13, 最終更新日: 2023-12-13)

主引用文献

Ekegren, J.K.,Ginman, N.,Johansson, A.,Wallberg, H.,Larhed, M.,Samuelsson, B.,Unge, T.,Hallberg, A.
Microwave-Accelerated Synthesis of P1'-Extended HIV-1 Protease Inhibitors Encompassing a Tertiary Alcohol in the Transition-State Mimicking Scaffold
J.Med.Chem., 49:1828-, 2006

PubMed Abstract: Two series of P1'-extended HIV-1 protease inhibitors comprising a tertiary alcohol in the transition-state mimic exhibiting Ki values ranging from 2.1 to 93 nM have been synthesized. Microwave-accelerated palladium-catalyzed cross-couplings were utilized to rapidly optimize the P1' side chain. High cellular antiviral potencies were encountered when the P1' benzyl group was elongated with a 3- or 4-pyridyl substituent (EC50 = 0.18-0.22 microM). X-ray crystallographic data were obtained for three inhibitors cocrystallized with the enzyme.

PubMed: 16509598
DOI: 10.1021/JM051239Z

実験手法

X-RAY DIFFRACTION (2.5 Å)