17-substituted steroids useful in cancer treatment
DC CAFCFirst Claim
1. A compound of the formula (I) ##STR27## wherein X represents the residue of the A, B and C rings of a steroid selected from the group consisting ofandrostan-3α
- - or 3β
-ol,androst-5-en-3α
- or 3β
-ol,androst-4-en-3-one,androst-2-ene,androst-4-ene,androst-5-ene,androsta-5,7-dien-3α
or 3β
-ol,androsta-1,4-dien-3-one,estra-1,3,5[10]-trien-3-ol,α
-androstan-3-one,androst-4-ene-3,11-dione,6-fluoroandrost-4-ene-3-one,androstan-4-ene-3,6-dione,each of which, where structurally permissible, can be further derivatised in one or more of the following ways;
to form 3-estersto have one or more carbon to carbon ring double bonds in any of the 5,6-, 6,7-, 7,8-, 9,11- and 11,12-positionsas 3-oximesas 3-methylenesas 3-carboxylatesas 3-nitrilesas 3-nitrosas 3-desoxy derivativesto have one or more hydroxy, halo, C1-4 -alkyl, trifluoro-methyl, C1-4 -alkoxy, C1-4 -alkanoyloxy, benzoyloxy, oxo, methylene or alkenyl substituents in the A, B, or C-ringto be 19-nor;
R represents a hydrogen atom or an alkyl group of 1-4 carbon atoms;
androsta-3,5-diene,androsta-3,5-diene-3-ol,estra-1,3,5[10]-triene andestra-1,3,5[10]-trien-3-ol,α
-androstan-3-one;
androst-4-ene-3,11-dione,6-fluoroandrost-4-ene-3-one,androstan-4-ene-3,6-dione,each of which, where structurally permissible, can be further derivatised in one or more of the following ways;
to form 3-estersto have one or more carbon or carbon ring double bonds in any of the 5,6-, 6,7-, 7,8-, 9,11- and 11,12-positionsas 3-oximesas 3-methylenesas 3-carboxylatesas 3-nitrilesas 3-nitrosas 3-desoxy derivativesto have one or more hydroxy, halo, C1-4 -alkyl, trifluoro-methyl, C1-4 -alkoxy, C1-4 -alkanoyloxy, benzoyloxy, oxo, methylene or alkenyl substituents in the A, B, or C-ringto be 19-nor;
R represents a hydrogen atom or an alkyl group of 1-4 carbon atoms;
R14 represents a hydrogen atom, a halogen atom or an alkyl group of 1 to 4 carbon atoms;
each of the R15 substituents independently represents a hydrogen atom or an alkyl or alkoxy group of 1-4 carbon atoms, a hydroxy group or an alkylcarbonyloxy group of 2 to 5 carbon atoms or together represent an oxo or methylene group or R14 and one of the R15 groups together represent a double bond and the other R15 group represents a hydrogen atom or an alkyl group of 1 to 4 carbon atoms; and
R16 represents a hydrogen atom, halogen atom, or an alkyl group of 1 to 4 carbon atoms, in the form of the free bases or pharmaceutically acceptable acid addition salts, but excluding 3β
-acetoxy-17-(3-pyridyl)androsta-5,14,16-triene, 3β
,15α
- and 3β
,15β
-diacetoxy-17-(3-pyridyl)androsta-5,16-diene and 3β
-methoxy-17-(3-pyridyl-5α
-androst-16-ene.
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Abstract
Compounds of the general formula (1) ##STR1## wherein X represents the residue of the A, B and C rings of a steroid, R represents a hydrogen atom or an alkyl group of 1 to 4 carbon atoms, R14 represents a hydrogen atom and R15 represents a hydrogen atom or an alkyl or alkoxy group of 1-4 carbon atoms, or a hydroxy or alkylcarbonyloxy group of 2 to 5 carbon atoms or R14 and R15 together represent a double bond, and R16 represents a hydrogen atom or an alkyl group of 1 to 4 carbon atoms, in the form of the free bases or phannaceutically acceptable acid addition salts, are useful for treatment of androgen-dependent disorders, especially prostatic cancer, and also oestrogen-dependent disorders such as breast cancer.
-
Citations
22 Claims
-
1. A compound of the formula (I) ##STR27## wherein X represents the residue of the A, B and C rings of a steroid selected from the group consisting of
androstan-3α - - or 3β
-ol,androst-5-en-3α
- or 3β
-ol,androst-4-en-3-one, androst-2-ene, androst-4-ene, androst-5-ene, androsta-5,7-dien-3α
or 3β
-ol,androsta-1,4-dien-3-one, estra-1,3,5[10]-trien-3-ol, α
-androstan-3-one,androst-4-ene-3,11-dione, 6-fluoroandrost-4-ene-3-one, androstan-4-ene-3,6-dione, each of which, where structurally permissible, can be further derivatised in one or more of the following ways; to form 3-esters to have one or more carbon to carbon ring double bonds in any of the 5,6-, 6,7-, 7,8-, 9,11- and 11,12-positions as 3-oximes as 3-methylenes as 3-carboxylates as 3-nitriles as 3-nitros as 3-desoxy derivatives to have one or more hydroxy, halo, C1-4 -alkyl, trifluoro-methyl, C1-4 -alkoxy, C1-4 -alkanoyloxy, benzoyloxy, oxo, methylene or alkenyl substituents in the A, B, or C-ring to be 19-nor; R represents a hydrogen atom or an alkyl group of 1-4 carbon atoms; androsta-3,5-diene, androsta-3,5-diene-3-ol, estra-1,3,5[10]-triene and estra-1,3,5[10]-trien-3-ol, α
-androstan-3-one;androst-4-ene-3,11-dione, 6-fluoroandrost-4-ene-3-one, androstan-4-ene-3,6-dione, each of which, where structurally permissible, can be further derivatised in one or more of the following ways; to form 3-esters to have one or more carbon or carbon ring double bonds in any of the 5,6-, 6,7-, 7,8-, 9,11- and 11,12-positions as 3-oximes as 3-methylenes as 3-carboxylates as 3-nitriles as 3-nitros as 3-desoxy derivatives to have one or more hydroxy, halo, C1-4 -alkyl, trifluoro-methyl, C1-4 -alkoxy, C1-4 -alkanoyloxy, benzoyloxy, oxo, methylene or alkenyl substituents in the A, B, or C-ring to be 19-nor; R represents a hydrogen atom or an alkyl group of 1-4 carbon atoms; R14 represents a hydrogen atom, a halogen atom or an alkyl group of 1 to 4 carbon atoms; each of the R15 substituents independently represents a hydrogen atom or an alkyl or alkoxy group of 1-4 carbon atoms, a hydroxy group or an alkylcarbonyloxy group of 2 to 5 carbon atoms or together represent an oxo or methylene group or R14 and one of the R15 groups together represent a double bond and the other R15 group represents a hydrogen atom or an alkyl group of 1 to 4 carbon atoms; and R16 represents a hydrogen atom, halogen atom, or an alkyl group of 1 to 4 carbon atoms, in the form of the free bases or pharmaceutically acceptable acid addition salts, but excluding 3β
-acetoxy-17-(3-pyridyl)androsta-5,14,16-triene, 3β
,15α
- and 3β
,15β
-diacetoxy-17-(3-pyridyl)androsta-5,16-diene and 3β
-methoxy-17-(3-pyridyl-5α
-androst-16-ene. - View Dependent Claims (3, 5, 9, 10, 11)
- - or 3β
-
2. A method of treating an androgen-dependent or estrogen-dependent disorder which comprises administering to a patient in a therapeutically effective dose a compound of the formula (1):
- ##STR28## wherein X represents the residue of the A, B and C rings of asteroid selected from the group consisting of
androstan-3α
- or 3β
-ol,androst-5-en-3α
- or 3β
-ol,androst-4-en-3-one, androst-2-ene, androst-4-ene, androst-5-ene, androsta-5,7-dien-3α
or 3β
-ol,androsta-1,4-dien-3-one, androsta-3,5-diene, androsta-3,5-dien-3-ol, estra-1,3,5[10]-triene and R14 represents a hydrogen atom, a halogen atom or an alkyl group of 1 to 4 carbon atoms; each of the R15 substituents independently represents a hydrogen atom or an alkyl or alkoxy group of 1-4 carbon atoms, a hydroxy group or an alkylcarbonyloxy group of 2 to 5 carbon atoms or together represent an oxo or methylene group or R14 and one of the R15 groups together represent a double bond and the other R15 group represents a hydrogen atom or an alkyl group of 1 to 4 carbon atoms; and R16 represents a hydrogen atom, halogen atom, or an alkyl group of 1 to 4 carbon atoms, in the form of the free bases or pharmaceutically acceptable acid addition salts. - View Dependent Claims (16, 17, 18, 19, 20, 21, 22)
- ##STR28## wherein X represents the residue of the A, B and C rings of asteroid selected from the group consisting of
-
4.
17-(3-Pyridyl)androsta-5,16-dien-3β - -ol,
17-(3-pyridyl)androsta-3,5,16-triene, 17-(3-pyridyl)androsta-4,16-dien-3-one, 17-(3-pyridyl)estra-1,3,5[10],16-tetraen-3-ol, 17-(3-pyridyl)-5α
-androst-16-en-3α
-oland their acid addition salts and 3-esters. - View Dependent Claims (12)
- -ol,
-
6.
17-(3-Pyridyl)-5α - -androst-16-en-3-one,
17-(3-pyridyl)-androsta-4,16-diene-3,11-dione, 17-(3-pyridyl)-androsta-3,5,16-trien-3-ol, 6α
- and 6β
-fluoro-17-(3-pyridyl)androsta-4,16-dien-3-one,17-(3-pyridyl)androsta-4,16-dien-3,6-dione, 3α
-trifluoromethyl-17-(3-pyridyl)androst-16-en-3β
-oland their acid addition salts and 3-esters. - View Dependent Claims (13)
- -androst-16-en-3-one,
-
7. 3β
- -Alkanoyloxy-17-(3-pyridyl)androsta-5,16-dienes in which the alkanoyloxy group has from 2 to 4 carbon atoms.
- View Dependent Claims (14)
-
8. 3β
- -Acetoxy-17-(3-pyridyl)androsta-5,16-diene.
- View Dependent Claims (15)
Specification