Estra-1,3,5 (10)-triene derivatives

A steroid sulfatase inhibitor comprising, as the active ingredient, an estra-1,3,5(10)-triene derivative which is represented by formula (I):

• 135
• <wherein
• R1 and R2 are the same or different and represent a hydrogen atom or a lower alkyl group, or R1 and R2 are combined with N adjacent thereto to form a nitrogen-containing heterocyclic group, or R1 and R2 are combined with N—SO2O—C═C—R3— adjacent thereto to form an oxathiazine dioxide ring or a dihydrooxathiazine dioxide ring;
• R3 represents a hydrogen atom, or is combined with R1 and R2 to form an oxathiazine dioxide ring or a dihydrooxathiazine dioxide ring;
• R4 represents a hydrogen atom, or is combined with R5 to form a bond;
• R5 represents a hydrogen atom, or is combined with R4 to form a bond, or is combined with R6 to form ═CR7R8 <wherein R7 represents a hydrogen atom or a substituted or unsubstituted lower alkyl group;
• R8 represents COR9 {wherein R9 represents a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heterocyclic group, or OR10 (wherein R10 represents a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group)}, X1NR11R12 <wherein R11 and R12 are the same or different and represent a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heterocyclic group, OR13 (wherein R13 represents a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group), or NR14R15 {wherein R14 and R15 are the same or different and represent a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heterocyclic group, COR16 (wherein R16 represents a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group), or SO2R17 (wherein R17 represents a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group)}, and X1 represents C═O or C═S>, CSR (wherein R18 represents a substituted or unsubstituted heterocyclic group), a substituted or unsubstituted aryl group, a substituted or unsubstituted heterocyclic group, CR19R20 (OH) (wherein R19 and R20 are the same or different and represent a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group), or CHR2R22 <wherein R21 represents a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group, R22 represents a substituted or unsubstituted aryl group, a substituted or unsubstituted heterocyclic group, or NR23R24 {wherein R23 and R24 are the same or different and represent a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heterocyclic group, X2R25(wherein R25 represents a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group, and X2 represents C═O or C═S), CO2R26 (wherein R26 represents a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group), X3NR27R28 (wherein R27 and R28 are the same or different and represent a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group, and X3 represents C═O or C═S), or SO2R29 (wherein R29 represents an amino group, a mono or di(lower alkyl)amino group, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group)}>>;
• R6 represents
• 1) a cyano group,
• 2) an amino group,
• 3) CHR30R31 <wherein R30 represents a hydrogen atom, or a substituted or unsubstituted lower alkyl group, R31 represents COR32 {wherein R32 represents a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heterocyclic group, or OR33 (wherein R33 represents a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group)}, X4NR34R35 <wherein R34 and R35 are the same or different and represent a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heterocyclic group, OR36 (wherein R36 represents a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group), or NR37R38 {wherein R37 and R38 are the same or different and represent a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heterocyclic group, COR39 (wherein R39 represents a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group), or SO2R40 (wherein R40 represents a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group)}, and X4 represents C═O or C═S>, CSR41 (wherein R41 represents a substituted or unsubstituted heterocyclic group), CR42R43(OH) (wherein R42 and R43 have the same meanings as defined for R19 and R20 above, respectively), or CHR44R45 (wherein R44 and R45 have the same meanings as defined for R21 and R22 above, respectively)>,
• 4) COR53 <wherein R53 represents a substituted lower alkyl group, a substituted lower cycloalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heterocyclic group, OR54 (wherein R54 represents a substituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group), or NR55R56 <wherein R55 represents a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heterocyclic group, or OR57 (wherein R57 represents a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group), and R56 represents a substituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heterocyclic group, OR58 (wherein R58 represents a substituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group), or NR59R60 {wherein R59 and R60 are the same or different and represent a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heterocyclic group, COR61 (wherein R61 represents a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group), or SO2R62 (wherein R62 represents a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group)}>>,
• 5) CSR63 {wherein R63 represents a substituted or unsubstituted heterocyclic group, or NR64R65 (wherein R64 and R65 have the same meanings as defined for R34 and R35 above, respectively)},
• 6) a substituted or unsubstituted aryl group,
• 7) a substituted or unsubstituted heterocyclic group,
• 8) CR71R72(OH) (wherein R71 represents a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group, and R72 represents a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group),
• 9) CHR73R74 (wherein R73 and R74 have the same meanings as defined for R21 and R22 above, respectively),
• 10) NR82R83 {wherein R82 represents a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group, and R83 represents a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heterocyclic group, COR84 (wherein R84represents asubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group), CSR85 (wherein R85 represents a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group), CO2R86 (wherein R86 represents a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group), X9NR87R88 (wherein R87 and R88 are the same or different and represent a hydrogen atom, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group, and X9 represents C═O or C═S), or SO2R89 (wherein R89 represents an amino group, a mono or di(lower alkyl)amino group, a substituted or unsubstituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group)}, or
• 11) NR90COR91 (wherein R90 represents a substituted lower alkyl group, a substituted or unsubstituted lower cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heterocyclic group, and R91 represents a hydrogen atom or a lower alkyl group), or
• 12) R6 is combined with R5 to form ═CR7R8 (wherein R7 and R8 have the same meanings as defined above, respectively)>, or a pharmaceutically acceptable salt thereof.