Steroidal and non-steroidal inhibitors of steroid 5α-reductase

A good deal of interest exists in developing inhibitors of steroid 5α-reductase (SR) as a therapy for pharmacological disorders associated with elevated levels of dihydrotestosterone (DHT), the product of SR action on testosterone (T). The recent identification of two isoforms of SR (types 1 and 2) has intensified this effort to include the design of isoform selective and dual isoform SR inhibitors. It is anticipated that such inhibitors will provide a more efficient and specific therapy for disorderd including benign prostatic hyperplasia, some prostatic cancers, certian skin disorders and male pattern baldness. The structural features which are responsible for the potency, isoform selectivity and SR species selectivity of the traditional classes of steroid-based inhibitors, typified by epristeride 7 and finasteride 15, have been identified. This information is being applied to the design of new classes of SR inhibitors. A new and rapidly expanding area of this work is the identification of non-steroidal inhibitors of SR. A survey of the main classes of SR inhibitor is followed by a review of the key structural features that are known to influence inhibitor potency and selectivity