2I4Q

Human renin/PF02342674 complex

Summary for 2I4Q

• Entry DOI: 10.2210/pdb2i4q/pdb
• Related: 2G1S 2G21 2G24
• Descriptor: 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)
• Functional Keywords: renin inhibitor, protein-ligand complex, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P00797
• Total number of polymer chains: 2
• Total formula weight: 74732.09

Authors

Holsworth, D.D.,Jalaie, M.,Zhang, E.,Mcconnell, P.,Mochalkin, I.,Finzel, B.C. (deposition date: 2006-08-22, release date: 2006-10-24, Last modification date: 2024-10-30)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.3 Å)