Piperidine-based renin inhibitors: upper chain optimization

Olivier Corminboeuf; Olivier Bezençon; Luboš Remeň; Corinna Grisostomi; Sylvia Richard-Bildstein; Daniel Bur; Lars Prade; Panja Strickner; Patrick Hess; Walter Fischli; Beat Steiner; Alexander Treiber

doi:10.1016/j.bmcl.2010.08.087

Piperidine-based renin inhibitors: upper chain optimization

Bioorg Med Chem Lett. 2010 Nov 1;20(21):6291-6. doi: 10.1016/j.bmcl.2010.08.087. Epub 2010 Aug 22.

Authors

Olivier Corminboeuf¹, Olivier Bezençon, Luboš Remeň, Corinna Grisostomi, Sylvia Richard-Bildstein, Daniel Bur, Lars Prade, Panja Strickner, Patrick Hess, Walter Fischli, Beat Steiner, Alexander Treiber

Affiliation

¹ Drug Discovery Chemistry & Biochemistry, Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, 4123 Allschwil, Switzerland.

PMID: 20843690
DOI: 10.1016/j.bmcl.2010.08.087

Abstract

The optimization of the 4-position of recently described new 3,4-disubstituted piperidine-based renin inhibitors is reported herein. The synthesis and characterization of compounds leading to the discovery of 11 (ACT-178882, MK-1597), a renin inhibitor with a suitable profile for development is described.

MeSH terms

Angiotensinogen / genetics
Animals
Animals, Genetically Modified
Cytochrome P-450 CYP3A
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Humans
Indicators and Reagents
Models, Molecular
Piperidines / chemical synthesis*
Piperidines / chemistry
Piperidines / pharmacology*
Rats
Renin / antagonists & inhibitors*
Renin / genetics
Stereoisomerism
Structure-Activity Relationship

Substances

Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Indicators and Reagents
Piperidines
Angiotensinogen
Cyp3a2 protein, rat
Cytochrome P-450 CYP3A
Renin