| 摘要 |
PURPOSE: A sulfoneamide derivative of the formula(I) is provided which is useful as an inhibitor of MMP(matrix metalloproteinase). And, its pharmaceutically acceptable salt and their manufacturing method are also provided. The sulfoneamide derivative selectively inhibits the activity of MMP in vitro. Therefore, MMP inhibitor containing it as an active ingredient can be used for the prevention and treatment of various diseases caused by the overexpression or overactivation of MMP. CONSTITUTION: The sulfoneamide derivative is represented by the formula(I), where R1 is hydrogen, C1-12 alkyl, carbocyclic aryl-low alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl-low alkyl, (oxo, amino or thio)C3-7 cycloalkyl, (oxo, amino or thio)C3-7 cycloalkyl-low alkyl, C2-12 low alkenyl, C2-12 low alkynyl, carbocyclic aryl, heterocyclic aryl, heterocyclic aryl-low alkyl, biaryl, halo low alkyl, biaryl-low alkyl arylalkyl, hydroxy-low alkyl, alkoxyalkyl, aryloxy-low alkyl, alkyl or aryl (thio, sulfinyl or sulfonyl) low alkyl, (amino, mono, or dialkylamino)low alkyl, acylamino low alkyl, (N-low alkyl-piperazino, or N-carbocyclic or heterocyclic aryl-low alkyl piperazino)-low alkyl or (morpholino, thiomorpholino, piperidino, pyrrolidine or piperidyl)-low alkyl; R2 amino acid residue, hydrogen, low alkyl, carbocyclic aryl-low alkyl, heterocyclic aryl-low alkyl, hydroxy-low alkyl, alkoxyalkyl, acyloxy-low alkyl, thio-low alkyl, alkyl or aryl (thio, sulfinyl or sulfonyl) low alkyl, (amino, mono or dialkylamino) low alkyl or acylamino low alkyl; R3 is hydrogen or C1-6 low alkyl; R4 is hydrogen, C1-12 alkyl, carbocyclic aryl-low alkyl, C3-7 cycloalkyl, C3-7 cycloalkyl-low alkyl, (oxo, amino or thio) C3-7 cycloalkyl, (oxo, amino or thio) C3-7 cycloalkyl-low alkyl, carbocyclic aryl, heterocyclic aryl, heterocyclic aryl-low alkyl, biaryl, halo low alkyl, acyloxy-low alkyl, alkyl or aryl (thio, sulfinyl or sulfonyl) low alkyl, (amino, mono or dialkylamino) low alkyl, acylamino low alkyl, (N-low alkyl-piperazino, N-carbocyclic or heterocyclic aryl-low alkyl piperazino)-low alkyl or (morpholino, thiomorpholino, piperidino, pyrrolidino or piperidyl)-low alkyl; R5 is -CO2H, -CONHOH, -PO3H2 or -CSH which is capable of binding to Zn; and X1 and X2 are N-R6(wherein, R6 is hydrogen, C1-6 low alkyl, aryl, heteroaryl or arylalkyl), S or O.
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