be categorized due to their structure. Many have been obtained from azasteroid inhibitors by taking away one or more rings from the steroid structure. Four main categories of nonsteroidal 5-ARIs have been described: Benzo(c)quinolizinones Benzo(f)quinolonone Piperidones Carboxylic acids Nonsteroidal inhibitors are thought to act as competitive inhibitors on the 5α-reductase isozymes, except for epristeride analogues (carboxylic acids), which are noncompetitive inhibitors. Bexlosteride falls into the category of benzo(f)quinolonones, and is probably the derivative that has come closest to being marketed. It functions as a 5-ARI1 inhibitor which inhibits testosterone stimulated LNCaP cell growth but without testosterone the compound shows no effect and was therefore never marketed. Structure–activity relationships 4-Azasteroids Many steroidal 5-ARIs have been researched but only 3 are marketed. Two of them are 4-azasteroids and will be covered here. As mentioned above, the third one, epristeride is only marketed in China and will not be covered here. The basic SAR of 4-azasteroids is shown below. For competitive inhibiting functions there are two functions considered crucial, 4-en-3-one function and a lipophilic 17β-side chain with one or more oxygen atoms. The main problems for 4-azasteroids is the rapid conversion into inactive 4,5-dihydro form, which is done by the enzyme. Finasteride is considered similar to the transition state of reduced testosterone and is thus a slow-offset, irreversible inhibitor. The similarity to the transition state is a formation of an enzyme-NADP-dihydrofinasteride adduct by rearrangement on the A-ring of the compound. Finasteride mainly inhibits the 5α-R2 (IC50=69 nM) and 5α-R3 (IC50=17.4 nM) with little inhibition of 5α-R1 (IC50=360 nM). As mentioned above, finasteride reduces prostatic DHT levels on a 70-90% range but the detailed reduction of DHT is 70.8% and 85% of intraprostatic DHT. Dutasteride, however, is a so-called dual inhibitor with both 5α-R1 and 5α-R2 inhibition. IC50 for 5α-R1 is 7 nM but 6 nM for 5α-R2. As mentioned above, it reduces DHT > 90% overall, or precisely 94.7% and for intraprostatic DHT the reduction is 97-99%. Dutasteride has also been found to inhibit 5α-R3, in vitro, with IC50=0.33 nM. The 2,5-difluorophenyl side chain on the D-ring of the compound shows significant lipophilic features and as increased lipophilicity enhances the potency of the compounds binding at pocket site, its potency is much greater than of finasteride. Finasteride is an unsaturated analogue of another 4-azasteroid, or 4-MA. 4-MA is known to have dual inhibiting features with good inhibition on 5α-R1 (IC50=1.7 nM) and 5α-R2