17-Methylene steroids, process for their production and pharmaceutical compositions that contain these compounds

A 17-Methylene steroid of formula I

• in which
• R4 is a halogen atom or a pseudohalogen,
• R10 is a hydrogen atom or a straight-chain or branched C1-C4 alkyl group,
• one of radicals R20 and R20a is a hydrogen atom or a methyl group, and the other radical is a fluorine, chlorine or bromine atom, an azido, cyano or rhodano group or hydroxymethyl.

A 17-Methylene steroid selected from the group consisting of

• 1) E-17-Chloromethylene-4-chloro-estr-4-en-3-one,
• 2) E-17-Cyanomethylene-4-chloro-estr-4-en-3-one,
• 3) Z-17-Cyanomethylene-4-chloro-estr-4-en-3-one,
• 4) Z-17-(1′)-Cyanoethylidene-4-chloro-estr-4-en-3one,
• 5) Z-17-Ethylidene-4-chloro-estr-4-en-3-one,
• 6) E-17-Ethylidene-4-chloro-estr-4-en-3-one,
• 7) E-17-Bromomethylene-4-chloro-estr-4-en-3-one,
• 8) Z-17-Chloroethylidene-4-chloro-estr-4-en-3-one,
• 9) Z-17-Bromoethylidene-4-chloro-estr-4-en-3-one,
• 10) E-17-Chloromethylene-4-cyano-androst-4-en-3-one,
• 11) E-17-Chloromethylene-4-chloro-androst-4-en-3-one,
• 12) E-17-(2′)-Hydroxyethylidene-4-chloro-estr-4-en-3-one, and
• 13) Z-17-(2′)-Hydroxyethylidene-4-chloro-estr-4-en-3-one.

A process for preparing a 17-methylene steroid of formula I

• in which
• R4 is a halogen atom or a pseudohalogen,
• R10 is a hydrogen atom or a straight-chain or branched C1-C4 alkyl group,
• R20 is a hydrogen atom, a straight-chain or branched C1-4 alkyl or hydroxy-C1-4 alkyl group, or a halogen atom or a pseudohalogen, and
• R20a is a hydrogen atom, comprising reacting a compound of formula II,
• in an aprotic solvent with an acid chloride to form a 17-methylene steroid of formula III,
• the 4,5-epoxide is generated with H2O2/NaOH, the 4,5-epoxide is then opened with a nucleophilic reagent, which is derived from a halogen atom or pseudohalogen, in a dipolar aprotic solvent to a halogen- or pseudohalogen hydrin, and optionally reacted with mineral acid, carboxylic acid or sulfonic acid in a protic or aprotic solvent with dehydration to a compound of formula IV,
• wherein R4 is a halogen atom or pseudohalogen, R10 is a hydrogen atom or a straight-chain or branched C1-C4 alkyl group,
• and R20 is a C1-4 alkyl or hydroxy-C1-4 alkyl group, a halogen atom or a pseudohalogen.

A process for preparing a 17-methylene steroid of formula I

• in which
• R4 is a halogen atom or a pseudohalogen,
• R10 is a hydrogen atom or a straight-chain or branched C1-C4 alkyl group,
• R20 and R20a are, independently of one another, a hydrogen atom, a straight-chain or branched C1-4 alkyl or hydroxy-C1-4 alkyl group, or
• one of radicals R20 and R20a is a hydrogen atom, a straight-chain or branched C1-4 alkyl or hydroxy-C1-4 alkyl group, and the other radical is a halogen atom or a pseudohalogen, comprising reacting a compound of formula V,
• with an acid chloride in an aprotic solvent to form a methylene steroid of formula VI,
• the 4,5-epoxide is generated with H2O2/NaOH, the 4,5-epoxide is then opened with a nucleophilic reagent, which is derived from a halogen atom or pseudohalogen, in a dipolar aprotic solvent to a halogen- or pseudohalogen hydrin, and optionally reacted with mineral acid, carboxylic acid or sulfonic acid in a protic or aprotic solvent with dehydration to a compound of formula VII,
• in which R4 is a halogen atom or pseudohalogen, R10 is a hydrogen atom or a straight-chain or branched C1-C4 alkyl group,
• and R20 is a C1-4 alkyl or hydroxy-C1-4 alkyl group, and R20a is a hydrogen atom, a halogen atom or a pseudohalogen.

A 17-methylene steroid of formula I

• in which
• R4 is a halogen atom or a pseudohalogen,
• R10 is a hydrogen atom or an ethyl, propyl, isopropyl, butyl, isobutyl, or tert-butyl group,
• R20 and R20a are, independently of one another, a hydrogen atom, a straight-chain or branched C1-4 alkyl or hydroxy-C1-4 alkyl group, or
• one of radicals R20 and R20a is a hydrogen atom, a straight-chain or branched C1-4 alkyl or hydroxy-C1-4 alkyl group, and the other radical is a halogen atom or a pseudohalogen,
• and a pharmaceutically compatible adjuvant or vehicle.

A 17-Methylene steroid of formula I

• in which
• R4 is a fluorine, bromine, or iodine atom or a pseudohalogen,
• R10 is a hydrogen atom or a straight-chain or branched C1-C4 alkyl group,
• R20 and R20a are, independently of one another, a hydrogen atom, a straight-chain or branched C1-4 alkyl or hydroxy-C1-4 alkyl group, or
• one of radicals R20 and R20a is a hydrogen atom, a straight-chain or branched C1-4 alkyl or hydroxy-C1-4 alkyl group, and the other radical is a halogen atom or a pseudohalogen.

A 17-Methylene steroid of formula I

• in which
• R4 is a halogen atom or a pseudohalogen,
• R10 is a hydrogen atom or a straight-chain or branched C1-C4 alkyl group,
• R20 is a hydrogen atom, a straight-chain or branched C1-4 alkyl or hydroxy-C1-4 alkyl group,
• R20a is a straight-chain or branched C1-4 alkyl or hydroxy-C1-4 alkyl group, or
• one of radicals R20 and R20a is a hydrogen atom, a straight-chain or branched C1-4 alkyl or hydroxy-C1-4 alkyl group, and the other radical is a halogen atom or a pseudohalogen.

A 17-Methylene steroid of formula I

• in which
• R4 is a pseudohalogen,
• R10 is a hydrogen atom or a straight-chain or branched C1-C4 alkyl group,
• R20 and R20a are, independently of one another, a hydrogen atom, a straight-chain or branched C1-4 alkyl or hydroxy-C1-4 alkyl group, or
• one of radicals R20 and R20a is a hydrogen atom, a straight-chain or branched C1-4 alkyl or hydroxy-C1-4 alkyl group, and the other radical is a halogen atom or a pseudohalogen.

A 17-Methylene steroid of formula I

• in which
• R4 is an azido, rhodano or cyano group,
• R10 is a hydrogen atom or a straight-chain or branched C1-C4 alkyl group,
• R20 and R20a are, independently of one another, a hydrogen atom, a straight-chain or branched C1-4 alkyl or hydroxy-C1-4 alkyl group, or
• one of radicals R20 and R20a is a hydrogen atom, a straight-chain or branched C1-4 alkyl or hydroxy-C1-4 alkyl group, and the other radical is a halogen atom or a pseudohalogen.

A 17-Methylene steroid of formula I

• in which
• R4 is a halogen atom or a pseudohalogen,
• R10 is a hydrogen atom or a straight-chain or branched C1-C4 alkyl group,
• one of R20 or R20a is a hydrogen atom, a straight-chain or branched C1-4 alkyl or hydroxy-C1-4 alkyl group, and the other of
• R20 or R20a is a straight-chain or branched C1-4 alkyl, a hydroxy-C1-4 alkyl group, a halogen atom or a pseudohalogen.