3SFC

Structure-Based Optimization of Potent 4- and 6-Azaindole-3-Carboxamides as Renin Inhibitors

Summary for 3SFC

• Entry DOI: 10.2210/pdb3sfc/pdb
• Related: 3OOT 3OQF 3OQK
• Descriptor: Renin, 2-acetamido-2-deoxy-beta-D-glucopyranose, GLYCEROL, ... (5 entities in total)
• Functional Keywords: renin human, aspartyl protease, renin inhibition, hypertension, beta barrel, pepsin-like protease, glycosylation, extracellular space, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P00797
• Total number of polymer chains: 2
• Total formula weight: 76906.60

Authors

Scheiper, B.,Matter, H.,Steinhagen, H.,Bocskei, Z.,Fleury, V.,McCort, G. (deposition date: 2011-06-13, release date: 2011-08-31, Last modification date: 2024-10-16)

Primary citation

Scheiper, B.,Matter, H.,Steinhagen, H.,Bocskei, Z.,Fleury, V.,McCort, G.
Structure-based optimization of potent 4- and 6-azaindole-3-carboxamides as renin inhibitors.
Bioorg.Med.Chem.Lett., 21:5480-5486, 2011

PubMed Abstract: The control of hypertension and associated cardiovascular risk factors is possible by selective inhibition of the aspartyl protease renin due to its unique position in the renin-angiotensin system. Starting from a previously disclosed series of potent and nonchiral indole-3-carboxamides, we further explored this motif by structure-based drug design guided by X-ray crystallography in combination with efficient parallel synthesis. This resulted in the discovery of 4- or 6-azaindole derivatives with remarkable potency for renin inhibition. The best compound from these series showed an IC(50) value of 1.3 nM.

PubMed: 21840218
DOI: 10.1016/j.bmcl.2011.06.114

Experimental method

X-RAY DIFFRACTION (2.1 Å)