Abstract
A series of cyclopenta[c]pyridine aldosterone synthase (AS) inhibitors were conveniently accessed using batch or continuous flow Kondrat'eva reactions. Preparation of the analogous cyclohexa[c]pyridines led to the identification of a potent and more selective AS inhibitor. The structure-activity-relationship (SAR) in this new series was rationalized using binding mode models in the crystal structure of AS.
MeSH terms
-
Chemistry Techniques, Synthetic
-
Cytochrome P-450 CYP11B2 / antagonists & inhibitors*
-
Cytochrome P-450 CYP11B2 / chemistry
-
Cytochrome P-450 Enzyme Inhibitors / chemical synthesis*
-
Cytochrome P-450 Enzyme Inhibitors / chemistry
-
Cytochrome P-450 Enzyme Inhibitors / pharmacology*
-
Humans
-
Models, Molecular
-
Protein Conformation
-
Pyridines / chemical synthesis*
-
Pyridines / chemistry
-
Pyridines / pharmacology*
-
Structure-Activity Relationship
Substances
-
Cytochrome P-450 Enzyme Inhibitors
-
Pyridines
-
Cytochrome P-450 CYP11B2