Cyclopentabenzofuran derivatives and their use
AssigneeBayer Aktiengesellschaft
InventorsWalter Guarnieri, Thomas Jaetsch, Andreas Schoop, Jorg Baumgarten, Axel Kretschmer, Horst-Peter Antonicek
Life of this patent
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Abstract
The invention relates to cyclopentabenzofuran derivatives and their use preparation, the use of cyclopentabenzofuran derivatives for the production of a medicament for the therapy of NF-κB-dependent diseases and medicaments which contain the cyclopentabenzofuran derivatives.
Claims12
Use of cyclopentabenzofuran derivatives of the formula (I)
- 132
- in which
- R1 and R3 independently of one another in each case represent hydrogen, halogen or alkyl,
- R2 and R4 independently of one another in each case represent halogen, alkyl or optionally substituted alkoxy,
- R5 represents hydroxyl, alkylamino or the radical —NR12—CHR13—COOR14, in which
- R12 represents hydrogen or alkyl,
- R13 represents one of the radicals of a natural or synthetic α-amino acid, where functional groups can optionally be present in protected form, or
- R12 and R13 together represent —(CH2)3— and —(CH2)4—, and
- R14 represents alkyl, benzyl or another C-terminal protective group,
- R6 represents hydrogen or
- R1 and R6 together represent oxygen (oxo),
- R7 and R8 in each case represent hydrogen,
- R9 represents optionally substituted phenyl or hetaryl,
- R10 represents hydrogen, halogen, alkyl or alkoxy and
- R11 represents hydrogen, halogen or alkyl,
- and of their salts for the production of a medicament for treating nuclear factor κB-dependent diseases.
Process for the preparation of cis-dihydrocyclopentabenzofurandiols of the formula (I-a)
- 133
- in which
- R1, R2, R3, R4, R9, R10 and R11 have the meanings indicated above, characterized in that ketoaldehydes of the formula (II-a)
- 134
- in which
- R1, R2, R3, R4, R9, R10 and R11 have the meanings indicated above,
- φare subjected to reductive cyclization.
Process for the preparation of tetrahydrocyclopentabenzofuranones of the formula (I-b)
- 135
- in which
- R1, R2, R3, R4, R9, R10 and R11 have the meanings indicated above, characterized in that dihydrocyclopentabenzofurandiols of the formula (I-a)
- 136
- in which
- R1, R2, R3, R4, R9, R10 and R11 have the meanings indicated above,
- φare oxidized.
Process for the preparation of trans-dihydrocyclopentabenzofurandiols of the formula (I-c)
- 137
- in which
- R1, R2, R3, R4, R9, R10 and R” have the meanings indicated above, characterized in that tetrahydrocyclopentabenzofuranones of the formula (I-b)
- 138
- in which
- R1, R2, R3, R4, R9, R10 and R11 have the meanings indicated above,
- φare reduced with alkali metal or tetraalkylammonium acyloxyborohydrides.
Process for the preparation of cyclopentabenzofuran derivatives of the formula (I-d)
- 139
- in which
- R1 to R11 have the meanings indicated above, with the restriction that at least one of the radicals R1, R3 and R11 represents halogen or alkyl,
- characterized in that this radical or these radicals are introduced by electrophilic aromatic substitution of compounds of the formula (I) indicated above in which the radical or radicals to be substituted represent(s) hydrogen.
Process for the preparation of cyclopentabenzofuran derivatives of the formula (I-e)
- 140
- in which
- R1 to R4 and R9 to R11 have the meanings indicated above and
- R5-1 represents alkylamino or the radical —NR12—CHR13—COOR14, in which R12, R13 and R14 have the meanings indicated above,
- φcharacterized in that tetrahydrocyclopentabenzofuranones of the formula (I-b)
- 141
- in which
- R1 to R4 and R9 to R11 have the meanings indicated above,
- φare reacted with primary amines or amino acid derivatives of the formula (III)
- H—R5-1 (III),
- in which
- R5-1 represents alkylamino or the radical —NR12—CHR13—COOR14, in which R12, R13 and R14 have the meanings indicated above,
- φin the presence of a reducing agent.
Dependencies are inferred from the claim text.