Claims for Patent: 5,604,213

Summary for Patent: 5,604,213

Title:	17-substituted steroids useful in cancer treatment
Abstract:	Compounds of the general formula (1) (I) 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.
Inventor(s):	Susan E. Barrie, Michael Jarman, Gerard A. Potter, Ian R. Hardcastle
Assignee:	BTG International Ltd
Application Number:	US08/315,882
Patent 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 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-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. 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 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, androsta-3,5-diene, androsta-3,5-dien-3-ol, estra-1,3,5[10]-triene andR14 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. 3. A compound according to claim 1, which is saturated and unsubstituted at the 11- and 12-positions. 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. 5. A compound according to claim 1 wherein R represents a hydrogen atom. 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. 7. 3β-Alkanoyloxy-17-(3-pyridyl)androsta-5,16-dienes in which the alkanoyloxy group has from 2 to 4 carbon atoms. 8. 3β-Acetoxy-17-(3-pyridyl)androsta-5,16-diene. 9. A pharmaceutical composition comprising a compound of claim 1 in association with a pharmaceutically acceptable carrier or diluent. 10. A pharmaceutical composition comprising a compound of claim 3 in association with a pharmaceutically acceptable carrier or diluent. 11. A pharmaceutical composition comprising a compound of claim 1 wherein R represent a hydrogen atom in association with a pharmaceutically acceptable carrier or diluent. 12. A pharmaceutical composition comprising a compound of claim 4 in association with a pharmaceutically acceptable carrier or diluent. 13. A pharmaceutical composition comprising a compound of claim 6 in association with a pharmaceutically acceptable carrier or diluent. 14. A pharmaceutical composition comprising a compound of claim 7 in association with a pharmaceutically acceptable carrier or diluent. 15. A pharmaceutical composition comprising a compound of claim 8 in association with a pharmaceutically acceptable carrier or diluent. 16. A method according to claim 2 wherein the patient has prostatic cancer. 17. A method according to claim 2 wherein the patient has breast cancer. 18. A method according to claim 2 wherein the compound defined in claim 2 is saturated and unsubstituted at the 11- and 12-positions. 19. A method according to claim 2 wherein the compound is selected from the group consisting of: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. 20. A method according to claim 2 wherein the compound is a 3β-alkanoyloxy-17-(3-pyridyl)androsta-5,16-diene wherein the alkanoyloxy group has 2 to 4 carbon atoms. 21. A method according to claim 2 wherein the compound is 3β-acetoxy-17-(3-pyridyl)androsta-5,16-diene. 22. An orally ingestible solid composition or a sterile injectable liquid composition comprising respectively a solid or liquid pharmaceutically acceptable carrier or diluent and a compound as defined by general formula (1) of claim 2.