Steroid 5a-reductases type 1 and

Finasteride has been clinically proved to reduce the median volume of the prostate in patients and is currently prescribed for the treatment of BPH. The compound also has demonstrated efficacy in the treatment of male pattern baldness and is prescribed for this indication as well. Subsequent to the discovery of finasteride, it was found that there are two isoforms of steroid 5a-reductase in mammals, type 1 and type 2. The type 2 isoform is primarily active in reproductive tissue, while the type 1 isoform contributes to DHT formation in the skin, liver, and reproductive tissue. Finasteride inhibits both isozymes in rats, but selectively inhibits the type 2 isozyme only in humans. It is hypothesized that dual inhibition of both isoforms of steroid 5a-reductase might prove more effective in treating BPH. Hence the GlaxoSmithKline group identified and developed dutasteride (Figure 8.18C). Dutasteride inactivates both human isoforms of steroid 5a-reductase by a mechanism similar to that described for finasteride (Bramson et al., 1997 see also the Web site www.avodart.com). Both finasteride and dutasteride have demonstrated clinical efficacy and are currently used in the treatment of BPH. 

Avodart1M Dutasteride 0.5 mg SEC Benign prostatic hyperplasia A selective inhibitor of both the type 1 and type 2 isoform of steroid 5a-reductase Mono-di-glycerides of caprylic/ capric acid, butylated hydroxytoluene Glaxosmithkline (GSK)... 

On the other hand, quinolinyl nucleophiles as the quinolinylzinc derivatives presented in the following example have been prepared by the in situ transmetallation of quinolinyllithium salts realized by direct halogen-metal exchange of 6-bromo quinoline derivative. The zinc salt was allowed to react with several aryl bromides, affording clean Negishi reactions for the formation of 6-substituted derivatives, which are potent inhibitors of steroid 5a reductases of types 1 and 2 ... 

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