14 β, 16, 17-methylene steroids as novel androgens

1. A (14β,17α)-7-(hydroxymethyl) steroid, wherein it carries a β-oriented, annellated cyclopropyl group which includes carbon atoms 16 and 17 of the steroid skeleton.

2. The (14β,17α)-17-(hydroxymethyl) steroid according to claim 1 , wherein it satisfies structural formula I:

wherein

R 1 is O, (H,H), (H,OR), NOR, with R being hydrogen, (C 1-6 )alkyl, (C 1-6 ) acyl;

R 2 is hydrogen, or (C 1-6 )alkyl;

R 3 is hydrogen; or R 3 is (C 1-6 )alkyl, (C 2-6 )alkenyl, or (C 2-6 )alkynyl, optionally substituted by halogen;

R 4 is hydrogen, or (C 1-6 )alkyl;

R 5 is hydrogen, (C 1-6 )alkyl, or (C 2-6 )alkenyl;

R 6 is (C 1-6 )alkyl;

R 1 is hydrogen, (C 1-6 )alkyl or (C 2-6 )alkenyl, or (C 1-6 )alkoxy;

R 8 is hydrogen, or (C 1-6 )alkyl;

R 9 and R 10 are independently hydrogen, (C 1-4 )alkoxy, halogen, (C 1-4 )alkyl, or (C 2-4 )alkenyl;

R 11 and R 12 are independently hydrogen, (C 1-6 ) alkyl, (C 2-6 )alkenyl, (C 3-6 )cycloalkyl, (C 5-6 )cycloalkenyl, or (C 2-6 )alkynyl, each optionally substituted by (C 1-4 )alkoxy, or halogen;

R 13 is hydrogen, SO 3 H, or (C 1-15 )acyl; and

the dotted lines indicate optional bonds.

3. A The steroid according to claim 2 , wherein R 4 is hydrogen; R 6 is methyl and; there is neither a Δ 5(10) nor a Δ 11(12) double bond.

4. A The steroid according to claim 3 , wherein

R 1 is O, (H,H), (H,OH);

R 2 is hydrogen, or methyl;

R 3 is hydrogen, methyl, ethyl or vinyl;

R 5 is hydrogen or methyl;

R 7 is hydrogen;

R 8 is hydrogen;

R 9 is hydrogen, (C 1-4 )alkoxy, halogen, (C 1-4 )alkyl, or (C 2-4 ) alkenyl;

R 10 is hydrogen;

R 11 and R 12 are independently hydrogen, (C 1-6 ) alkyl, (C 2-6 )alkenyl, (C 3-6 )cycloalkyl, (C 5-6 )cycloalkenyl, or (C 2-6 )alkynyl each optionally substituted by (C 1-4 )alkoxy, or halogen.

5. A The steroid according to claim 4 , wherein

one of R 11 and R 12 is hydrogen and the other is hydrogen or 20S methyl, 20S ethyl or 20S ethynyl.

6. A The steroid according to claim 5 , wherein

R 2 is hydrogen;

R 5 is hydrogen;

R 9 is hydrogen;

R 11 and R 12 are (H,20S methyl) and the steroid does not have a Δ 9(10) double bond.

7. A The steroid according to claim 2 , wherein R 3 is hydrogen or methyl.

8. A The steroid according to claim 2 , wherein R 13 is hydrogen or acyl; R 1 is O or (H,βOH) and the compound has a Δ 4(5) double bond.

9. The steroid according to claim 8 , wherein it is (7α,14β,16α,17α)-16,17-dihydro-17-(hydroxymethyl)-7-methyl-3′H-cyclopropa[16,17]estra-4,16-dien-3-one or (3β,7α,14β,16α,17α)-16,17-dihydro-17-(hydroxymethyl)-7-methyl-3′H-cyclopropa[16,17]estra-4,16-dien-3-ol.

10. A pharmaceutical composition, comprising:

the (14β,17α)-17-(hydroxymethyl) steroid according to claim 1 , and

a pharmaceutically acceptable carrier.

11. A kit for male contraception, comprising:

a means for administering a progestagen and

a means for administering an androgen, wherein the androgen is a (14β,17α)-17-(hydroxymethyl) steroid according to claim 1 .

12. A method of treating androgen-deficiency, comprising:

administering to a patient suffering from androgen-deficiency an effective amount of the (14β,17α)-17-(hydroxymethyl) steroid according to claim 1 .

13. A method of contraception, comprising,

administering to a male patient an effective amount of the (14β,17α)-17-(hydroxymethyl) steroid according to claim 1 .