2I4Q

Human renin/PF02342674 complex

2I4Q の概要

• エントリーDOI: 10.2210/pdb2i4q/pdb
• 関連するPDBエントリー: 2G1S 2G21 2G24
• 分子名称: Renin, (2S)-6-(2,4-DIAMINO-6-ETHYLPYRIMIDIN-5-YL)-2-(3,5-DIFLUOROPHENYL)-4-(3-METHOXYPROPYL)-2-METHYL-2H-1,4-BENZOXAZIN-3(4H)-ONE (3 entities in total)
• 機能のキーワード: renin inhibitor, protein-ligand complex, hydrolase
• 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: 74732.09

構造登録者

Holsworth, D.D.,Jalaie, M.,Zhang, E.,Mcconnell, P.,Mochalkin, I.,Finzel, B.C. (登録日: 2006-08-22, 公開日: 2006-10-24, 最終更新日: 2024-10-30)

主引用文献

Powell, N.A.,Ciske, F.L.,Cai, C.,Holsworth, D.D.,Mennen, K.,Van Huis, C.A.,Jalaie, M.,Day, J.,Mastronardi, M.,McConnell, P.,Mochalkin, I.,Zhang, E.,Ryan, M.J.,Bryant, J.,Collard, W.,Ferreira, S.,Gu, C.,Collins, R.,Edmunds, J.J.
Rational design of 6-(2,4-diaminopyrimidinyl)-1,4-benzoxazin-3-ones as small molecule renin inhibitors.
Bioorg.Med.Chem., 15:5912-5949, 2007

PubMed Abstract: We report the design and synthesis of a series of 6-(2,4-diaminopyrimidinyl)-1,4-benzoxazin-3-ones as orally bioavailable small molecule inhibitors of renin. Compounds with a 2-methyl-2-aryl substitution pattern exhibit potent renin inhibition and good permeability, solubility, and metabolic stability. Oral bioavailability was found to be dependent on metabolic clearance and cellular permeability, and was optimized through modulation of the sidechain that binds in the S3(sp) subsite.

PubMed: 17574423
DOI: 10.1016/j.bmc.2007.05.069

実験手法

X-RAY DIFFRACTION (2.3 Å)