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Bioorg Med Chem Lett. 2011 Apr 15;21(8):2430-6. doi: 10.1016/j.bmcl.2011.02.067. Epub 2011 Feb 18.

The discovery and synthesis of potent zwitterionic inhibitors of renin.

Author information

1
Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe Claire-Dorval, Québec, Canada H9R 4P8. renee.aspiotis@sympatico.ca

Abstract

The incorporation of a carboxylic acid within in a series of 3-amido-4-aryl substituted piperidines (represented by general structure 32) led to the discovery of potent, zwitterionic, renin inhibitors with improved off-target profiles (CYP3A4 time-dependent inhibition and hERG affinity) relative to analogous non-zwitterionic inhibitors of the past (i.e., 3). Strategies to address the oral absorption of these zwitterions are also discussed within.

PMID:
21429746
DOI:
10.1016/j.bmcl.2011.02.067
[Indexed for MEDLINE]

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