Evaluation of 4'-substituted bicyclic pyridones as non-steroidal inhibitors of steroid 5a-reductase
Date
2007
Authors
McCarthy, A.
Hartmann, R.
Abell, A.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Bioorganic and Medicinal Chemistry Letters, 2007; 17(13):3603-3607
Statement of Responsibility
Anna R. McCarthy, Rolf W. Hartmann and Andrew D. Abell
Conference Name
Abstract
4′-Substituted bicyclic pyridones were prepared and evaluated as non-steroidal inhibitors of type 1 and 2 steroid 5greek small letter alpha-reductase (SR). A range of 4′-substituents were incorporated into the bicyclic scaffold to investigate SAR within and across different classes of non-steroidal inhibitors of SR. Bicyclic pyridones containing a 4′-benzoyl or long carbon chain tether showed more potent inhibition against type 1 SR than inhibitors with N-substituted acetamide groups in the 4′-position. SAR derived from 4′-substituted bicyclic pyridones reported here do not correlate with SAR derived from known potent 4′-substituted biaryl acid SR inhibitors. A 4′-benzoyl group is favoured by the active site in both isozymes.