Aromatic esters of progesterone as 5α-reductase and prostate growth inhibitors

Figures & data

Figure 1.  Structures of the reference compounds 1 testosterone, 2 dihydrotestosterone, 3 finasteride, 4 dutasteride, 5 4-MA, 6 mibolerone.

Table I.  Weight of prostate glands±standard deviation from animals receiving s.c. treatments for 6 days of differenct compounds.

Treatment	Weight of prostate (mg)
Intact	224.8 ± 35
Control	56.3 ± 12.5^*
T	125.8 ± 27
T + F	80.1 ± 10.4^*
T + 9a	89.2 ± 10.5
T + 9b	85.85 ± 7.6
T + 10a	80.0 ± 11.1^*
T + 10b	74.0 ± 9.6^*

F, finasteride

* Significant differences between controls and treated groups (P < 0.05)

Figure 2.  Synthesis of steroidal compounds 9a, 9b, 10a, 10b and their preparation from the commercially available 17α-acetoxyprogesterone.

Table II.  The IC₅₀ values for finasteride and the synthesized steroids 9a, 9b, 10a, 10b with human prostate 5α–reductase enzyme. They represent the concentration of the steroid that inhibits 50% of 5α–reductase activity and were determined as described in the Experimental section.

Compound	IC50 [nM]
	8.5
	360
	370
	13
	4.9

Figure 3.  Inhibition of [³H] mibolerone binding to the androgen receptors by unlabeled steroids, as described in Methods section.