| 摘要 |
Diseases mediated by tumor necrosis factor- alpha (TNF- alpha ) are treated using beta -carboline derivatives (I), i.e. harmine or its derivatives. Some compounds (I) are new. beta -carboline derivatives of formula (I) or their salts are used for the preparation of medicaments for treating diseases mediated by TNF- alpha . R1 = H, alkyl or CH2R6; R6 = cycloalkyl (optionally substituted phenyl) alkoxycarbonyl or optionally alkyl-substituted alkyleneaminocarbonyl (cyclic aminocarbonyl), in which the alkylene chain is optionally interrupted by O, S or N; R2 = H, alkyl, CH2R7, optionally substituted benzoyl or S(O)nR8; R7 = CN, dialkoxymethyl, optionally substituted phenyl, optionally substituted phenylalkyl, alkoxy, alkynyloxy, alkoxycarbonyl, dialkylaminocarbonyl or N-alkyl-N-alkoxycarbonylamino; R8 = alkyl or optionally substituted phenyl; n = 1 or 2; R3 = H, halo, OH, alkyl, optionally substituted benzoylcarbonyl or CH2R9; R9 = 1-hydroxycycloalkyl (optionally substituted by methyl); cycloalkylmethyl; or benzyl or alpha -hydroxybenzyl (both optionally ring-substituted); R4 = H, halo or NO2; and R5 = H, halo, NO2 or alkylcarbonyl. An Independent claim is included for (I) and their salts as new compounds, where n, R4, R5 and R8 are as above and: (A) R1 = alkyl or CH2R6; R6 = as above; R2 = CH2R7, optionally substituted benzoyl or S(O)nR8; R7 = as above except that optionally substituted phenyl is replaced by phenyl substituted by one or more of halo, CN, 1-4C alkyl or 1-4C alkoxy (both optionally substituted by F or Cl), NO2, NH2 or mono- or di-(1-4C)alkylamino; R3, R9 = as above; (B) R1 = CH2R6; R6 = as above but not unsubstituted phenyl; R2 = H, alkyl or benzyl; R3, R9 = as above; or (C) R1 = alkyl or benzyl; R2 = H, alkyl or benzyl; R3 = halo, optionally substituted benzoylcarbonyl or CH2R9; and R9 = cycloalkylmethyl, ring-substituted benzyl or optionally substituted alpha -hydroxybenzyl.
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