2G1Y

Ketopiperazine-Based Renin Inhibitors: Optimization of the "C" Ring

Summary for 2G1Y

• Entry DOI: 10.2210/pdb2g1y/pdb
• Related: 2G1N 2G1O 2G1R 2G1S 2G20 2G21 2G22 2G24 2G26 2G27
• Descriptor: Renin, 2-acetamido-2-deoxy-beta-D-glucopyranose, 6-(2,4-DIAMINO-6-ETHYLPYRIMIDIN-5-YL)-4-(3-METHOXYPROPYL)-2,2-DIMETHYL-2H-1,4-BENZOXAZIN-3(4H)-ONE, ... (4 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: 74345.80

Authors

Holsworth, D.D.,Jalaiea, M.,Zhanga, E.,Mcconnella, P. (deposition date: 2006-02-15, release date: 2006-06-13, Last modification date: 2024-11-20)

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 (2.5 Å)