| 摘要 |
N-benzylindol-3-yl glyoxylic acid derivatives (I) or their acid addition salts, are new. N-benzylindol-3-yl glyoxylic acid derivatives of formula (I), or their acid addition salts, are new. R = nitro or amino is optionally substituted by amino is substituted by 1 or 2 1-6C alkyl or cycloalkyl; 1-6C acyl; phenyl(1-6C)alkyl; (hetero)aroyl; 1-6C alkylsulfonyl; arylsulfonyl; Z; Boc; 9-fluorenylmethoxycarbonyl; triphenyl; 2-(4-pyridyl)ethoxycarbonyl; diphenylmethylsilyl; or it is maleimido, succinimido or phthalimido; also, when R1 = hydrogen, Me, benzyl, Z, Boc or acetyl, R may be N-linked Gly, Ala, Leu, Ile, Ser, Phe, His, Arg, Lys, Asn or Glu. In R1, substituents on alkyl are phenyl (optionally substituted by one or more halo, 1-6C alkyl, 3-7C cycloalkyl, carboxy, 1-6C alkoxycarbonyl, trifluoromethyl, hydroxy, MeO, EtO, benzyloxy) or benzyl (optionally ring substituted by one or more 1-6C alkyl, halo or trifluoromethyl); R1 = H, 1-6C alkyl (optionally substituted), benzyloxycarbonyl (Z), tert-butoxycarbonyl (Boc) or acetyl; R2 = phenyl (optionally substituted by one or more 1-6C alkyl or alkoxy, CN, halo, trifluoromethyl, hydroxy, benzyloxy, nitro, amino (optionally substituted by 1-6C alkyl or alkoxycarbonyl), carboxy or 1-6C alkoxycarbonyl; substituents for 2-pyrimidinyl are one or more Me; those for quinolinyl are one or more of 1-6C alkyl, halo, nitro, amino or 1-6C alkylamino, and ring carbons in the pyridylmethyl component of quinolyl and quinolylmethyl may be substituted by 1-6C alkyl, alkoxy or alkoxycarbonylamino, nitro or amino), pyridinyl (optionally substituted by R5 and R6, optionally as N-oxide), or (all optionally substituted) 2- or 4-pyrimidinyl, quinolinyl, 3- or 4-quinolinylmethyl, also allylaminocarbonyl-2-methylprop-1-yl, or a wide variety of other substituents, depending on nature of R1, or R1 and R2 together complete 4-R7-piperazino or homopiperazino. When R1 = H, Me, benzyl, Z, Boc or acetyl, R2 may be N-linked Gly, Ala, Leu, Ile, Ser, Phe, His, Arg, Lys, Asn or Glu, or the residue of any natural or non-natural amino acid (optionally protected), and if R2 = residue of Asp or Glu, the second, non-bound carboxy may be as free acid or 1-6C alkyl ester; R5, R6 = 1-6C alkyl or alkoxy, 3-7C cycloalkyl, nitro, amino, hydroxy, halo, trifluoromethyl, ethoxycarbonylamino or carboxy(1-4C)alkoxy; R7 = alkyl, phenyl (optionally substituted by one or more 1-6C alkyl or alkoxy, halo, nitro, amino or 1-6C alkylamino), benzhydryl or bis-p-fluorobenzhydryl; R3, R4 = H, 1-6C alkyl, alkoxy or alkanoyl, 3-7C cycloalkyl, halo, benzyloxy, nitro, amino (optionally substituted by 1 or 2 1-4C alkyl), 1-6C alkoxycarbonylamino or 1-6C alkoxycarbonylamino(1-6C) alkyl; and Z = O or S. Independent claims are also included for: (a) pharmaceutical composition comprising (I) or its salt, optionally also carriers, diluents and/or auxiliaries; and (b) galenical formulations comprising (I) or its salt as (coated) tablets, solutions for infusion, capsules, ampoules, suppositories, plasters, inhalable powders, suspensions, creams or ointments.
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