3SFC

Structure-Based Optimization of Potent 4- and 6-Azaindole-3-Carboxamides as Renin Inhibitors

3SFC の概要

• エントリーDOI: 10.2210/pdb3sfc/pdb
• 関連するPDBエントリー: 3OOT 3OQF 3OQK
• 分子名称: Renin, 2-acetamido-2-deoxy-beta-D-glucopyranose, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: renin human, aspartyl protease, renin inhibition, hypertension, beta barrel, pepsin-like protease, glycosylation, extracellular space, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P00797
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 76906.60

構造登録者

Scheiper, B.,Matter, H.,Steinhagen, H.,Bocskei, Z.,Fleury, V.,McCort, G. (登録日: 2011-06-13, 公開日: 2011-08-31, 最終更新日: 2024-10-16)

主引用文献

Scheiper, B.,Matter, H.,Steinhagen, H.,Bocskei, Z.,Fleury, V.,McCort, G.
Structure-based optimization of potent 4- and 6-azaindole-3-carboxamides as renin inhibitors.
Bioorg.Med.Chem.Lett., 21:5480-5486, 2011

PubMed Abstract: The control of hypertension and associated cardiovascular risk factors is possible by selective inhibition of the aspartyl protease renin due to its unique position in the renin-angiotensin system. Starting from a previously disclosed series of potent and nonchiral indole-3-carboxamides, we further explored this motif by structure-based drug design guided by X-ray crystallography in combination with efficient parallel synthesis. This resulted in the discovery of 4- or 6-azaindole derivatives with remarkable potency for renin inhibition. The best compound from these series showed an IC(50) value of 1.3 nM.

PubMed: 21840218
DOI: 10.1016/j.bmcl.2011.06.114

実験手法

X-RAY DIFFRACTION (2.1 Å)