Patent EA-003092-B1 (EA)
Title: STEROIDS WITH A FLUORINATED 17alpha-ALKYL CHAIN WITH ANTIGESTAGENIC ACTION
Inventor: SCHWEDE WOLFGANG
IPC: C07J41/00
Filed: 1998-02-09
Abstract: 1. 17α-Fluoroalkyl steroids of general formula I   in which R<1> stands for a methyl or ethyl group, R<2> stands for a radical of formula CnFmHo, whereby n is 2, 3, 4, 5 or 6, m > 1 and m+o = 2n+1, R<3> stands for a free etherified or esterified hydroxy group, R<4> and R<5> each stand for a hydrogen atom, together for an additional bond or a methylene group, St stands for a steroidal ABC-ring system of partial formula A, B or C     in which R<6> means a hydrogen atom, a straight-chain C1-C4 alkyl group or branched C3-C4 alkyl group or a halogen atom, R<7> means a hydrogen atom, a straight-chain C1-C4 alkyl group or a branched C3-C4 alkyl group, or if St stands for a steroidal ABC-ring system A or B, in addition R<6> and R<7> together mean an additional bond, X means an oxygen atom, a hydroxyimino grouping = N-OH or two hydrogen atoms, R<8> means a radical Y or an aryl radical that is optionally substituted in several places with a group Y, whereby Y is a hydrogen atom, a halogen atom, an -OH, -NO2, -N3, -CN, -NR<9a>R<9b>, -NHSO2R<9>, -CO2R<9>, C1-C10 alkyl, C1-C10 alkoxy, C1-C10 alkanoyloxy, benzoyloxy, C1-C10 alkanoyl, C1-C10 hydroxyalkyl or benzoyl group, and R<9a> and R<9b> are the same or different and in the same way as R<9> represent a hydrogen atom or a C1-C10 alkyl group, and for -N<9a>R<9b> radicals, also their physiologically compatible salts with acids and for -CO2R<9> radicals with R<9> meaning hydrogen, and also their physiologically compatible salts with bases. 2. 17α-Fluoroalkyl steroids according to claim 1, in which St stands for a steroidal ring system of partial formula A. 3. 17α-Fluoroalkyl steroids according to claim 1, in which St stands for a steroidal ring system of partial formula B. 4. 17α-Fluoroalkyl steroids according to claim 1, in which St stands for a steroidal ring system of partial formula C. 5. 17α-Fluoroalkyl steroids according to claim 1, in which n = 2, 3 or 4. 6. 17α-Fluoroalkyl steroids according to claim 5, in which o = 0. 7. 17α-Fluoroalkyl steroids according to claim 6, in which n = 2. 8. 17α-Fluoroalkyl steroids according to claim 1, in which R<3> is a free hydroxy group. 9. 17α-Fluoroalkyl steroids according to claim 1, in which R<8> stands for radical Y. 10. 17α-Fluoroalkyl steroids according to claim 9, in which Y stands for a C1-C10 acyl group. 11. 17α-Fluoroalkyl steroids according to claim 10, in which Y stands for a formyl, acetyl or propionyl group. 12. 17α-Fluoroalkyl steroids according to claim 9, in which Y stands for a C1-C10 hydroxyalkyl group. 13. 17α-Fluoroalkyl steroids according to claim 12, in which Y stands for a hydroxymethyl or 1-hydroxyethyl group. 14. 17α-Fluoroalkyl steroids according to claim 9, in which Y stands for a hydroxy group. 15. 17α-Fluoroalkyl steroids according to claim 9, in which Y stands for an acetyloxy group. 16. 17α-Fluoroalkyl steroids according to claim 9, in which Y stands for a methoxycarbonyl group. 17. 17α-Fluoroalkyl steroids according to claim 1, in which R<8> stands for an aryl radical that is substituted with a group Y. 18. 17α-Fluoroalkyl steroids according to claim 17, in which the aryl radical is a phenyl, naphthalinyl, furanyl, benzofuranyl, thienyl or pyridinyl radical. 19. 17α-Fluoroalkyl steroids according to claim 18, in which R<8> is a 4-cyanophenyl radical. 20. 17α-Fluoroalkyl steroids according to claim 18, in which R<8> is a 4-halophenyl radical. 21. 17α-Fluoroalkyl steroids according to claim 20, in which R<8> is a 4-fluorophenyl radical. 22. 17α-Fluoroalkyl steroids according to claim 1, in which R<4> and R<5> each stand for a hydrogen atom. 23. 17α-Fluoroalkyl steroids according to claim 1, in which R<4> and R<5> together stand for an additional bond. 24. 17α-Fluoroalkyl steroids according to claim 1, in which R<6> and R<7> are each a hydrogen atom. 25. 17α-Fluoroalkyl steroids according to claim 1, namely 11β-(4-Acetylphenyl)-17β-hydroxy-17α-(1,1,2,2,2-pentafluoroethyl)estr-4-en-3-one; 11β-(4-Acetylphenyl)-17β-hydroxy-17α-(1,1,2,2,2-pentafluoroethyl)estra-4,9-dien-3-one; 11β-(4-Acetylphenyl)-17β-hydroxy-17α-(1,1,2,2,2-pentafluoroethyl)estra-4,9,15-trien-3-one; 6'-acetyl-9,11α-dihydro-17β-hydroxy-17α-(1,1,2,2,2-pentafluoroethyl)-4'H-naphth[3',2',1':10,9,11]estr-4-en-3-one; 4-[9,11α-dihydro-17β-hydroxy-3-oxo-17α-(1,1,2,2,2-pentafluoroethyl)-4'H-naphth[3',2',1':10,9,11]estr-4-en-6'-yl] benzonitrile;  9,11α-dihydro-6'-(4-fluorophenyl)-17β-hydroxy-17α-(1,1,2,2,2-pentafluoroethyl)-4'H-naphth[3',2',1':10,9,11]estr-4-en-3-one; 17β-hydroxy-11β-(4-hydroxyphenyl)-17α-(1,1,2,2,2-pentafluoroethyl)estra-4,9-dien-3-one; 11β-[4-(acetyloxy)phenyl]-17β-hydroxy-17α-(1,1,2,2,2-pentafluoroethyl)estra-4,9-dien-3-one; 17β-hydroxy-11β-[4-(hydroxymethyl)phenyl]-17α-(1,1,2,2,2-pentafluoroethyl)estra-4-en-3-one; 4-[17β-hydroxy-3-oxo-17α-(1,1,2,2,2-pentafluoroethyl)estra-4,9-dien-11β-yl]benzaldehyde; 4-[17β-hydroxy-3-oxo-17α-(1,1,2,2,2-pentafluoroethyl)estra-4,9-dien-11β-yl]benzoic acid methyl ester; 17β-hydroxy-11β-[4-(1-hydroxyethyl)phenyl]-17α-(1,1,2,2,2-pentafluoroethyl)estra-4,9-dien-3-one. 26. Pharmaceutical preparations that contain at least one 17α-fluoroalkyl steroid of general formula I according to claim 1 as well as a pharmaceutically compatible vehicle. 27. Pharmaceutical preparations according to claim 26 that in addition contain at least one compound with antiestrogenic action. 28. Use of the 17α-fluoroalkyl steroids of general formula I according to claim 1 for the production of pharmaceutical agents. 29. Use according to claim 28 in addition with a compound with antiestrogenic action.