2FS4

Ketopiperazine-Based Renin Inhibitors: Optimization of the C ring

Summary for 2FS4

• Entry DOI: 10.2210/pdb2fs4/pdb
• Descriptor: Renin, (6R)-6-({[1-(3-HYDROXYPROPYL)-1,7-DIHYDROQUINOLIN-7-YL]OXY}METHYL)-1-(4-{3-[(2-METHOXYBENZYL)OXY]PROPOXY}PHENYL)PIPERAZIN-2-ONE (3 entities in total)
• Functional Keywords: protein-ligand complexes, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P00797
• Total number of polymer chains: 2
• Total formula weight: 73720.17

Authors

Holsworth, D.D.,Cai, C.,Cheng, X.-M.,Cody, W.L.,Downing, D.M.,Erasga, N.,Lee, C.,Powell, N.A.,Edmunds, J.J.,Stier, M.,Jalaie, M.,Zhang, E.,McConnell, P.,Ryan, M.J.,Bryant, J.,Li, T.,Kasani, A.,Hall, E.,Subedi, R.,Rahim, M.,Maiti, S. (deposition date: 2006-01-20, release date: 2006-06-13, Last modification date: 2024-10-30)

Primary citation

Holsworth, D.D.,Cai, C.,Cheng, X.M.,Cody, W.L.,Downing, D.M.,Erasga, N.,Lee, C.,Powell, N.A.,Ednunds, J.J.,Stier, M.,Jalaie, M.,Zhang, E.,McConnell, P.,Ryan, M.J.,Bryant, J.,Li, T.,Kasani, A.,Hall, E.,Subedi, R.,Rahim, M.,Maiti, S.
Ketopiperazine-Based Renin Inhibitors: Optimization of the "C" Ring
BIOORG.MED.CHEM.LETT., 16:2500-2504, 2006

PubMed Abstract: A systematic investigation of the S3 sub-pocket activity requirements was conducted. It was observed that linear and sterically small side chain substituents are preferred in the S3 sub-pocket for optimal renin inhibition. Polar groups in the S3-sub-pocket were not well tolerated and caused a reduction in renin inhibitory activity. Further, compounds with clog P's < or = 3 demonstrated a dramatic reduction in CYP3A4 inhibitory activity.

PubMed: 16480874
DOI: 10.1016/j.bmcl.2006.01.084

Experimental method

X-RAY DIFFRACTION (2.2 Å)