2G1O

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

Summary for 2G1O

• Entry DOI: 10.2210/pdb2g1o/pdb
• Related: 2G1N 2G1R 2G1S 2G1Y 2G20 2G21 2G22 2G24 2G26 2G27
• Descriptor: Renin, 2-acetamido-2-deoxy-beta-D-glucopyranose, 6-ETHYL-5-[9-(3-METHOXYPROPYL)-9H-CARBAZOL-2-YL]PYRIMIDINE-2,4-DIAMINE, ... (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: 74325.81

Authors

Holsworth, D.D.,Zhanga, E. (deposition date: 2006-02-14, release date: 2006-06-13, Last modification date: 2020-07-29)

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 (2.7 Å)