Indole and indazole compounds as an inhibitor of cellular necrosis

A method of inhibiting necrosis in tissue selected from the group consisting of liver, pancreas and cartilage, comprising:

• administering an effective amount of a compound of formula (1) or pharmaceutically acceptable salt or enantiomer or diastereomer thereof to a subject in need thereof, wherein the compound is an indole compound of the following formula (1):
• in which
• n denotes a number of 1 to 3,
• m denotes 0 or 1,
• A represents phenyl,
• X represents C or CH, with the proviso that m is 1 when X is C,
• R1 represent hydrogen, alkyl, —(CH2)rNR7R8, or —(CH2)rCO2H, wherein r denotes a number of 1 to 5, and R7 and R8 independently of one another represent hydrogen, alkyl or alkylcarbonyl, or may together form an optionally alkyl-substituted alkylene chain wherein optionally one methylene is replaced by N atom,
• R2 represents hydrogen, halogen, cyano, nitro, hydroxy, alkyl, alkoxy or trialkylsilyl, represents —(CH2)pCO2R7, —(CH2)pOR7, —(CH2)pNR7R8, —NHR10, —N(H)S(O)2R7, —NHC(O)R10, —(CH2)pS(O)2R7 or (CH2)p-heterocycle-R10, wherein p denotes a number of 0 to 3, R7 and R8 are as defined above, R10 represents hydrogen, oxo, alkylsulfonyl, alkylcarbonyl, alkyloxycarbonyl, alkylaminocarbonyl, alkoxy, alkyl or heterocycle,
• R3 represents hydrogen, cyano, halogen, alkyl or phenyl, or represents —(CH2)n-heterocycle or —(CH2)n-aryl, wherein n denotes a number of 0 to 3,
• R4 represents —YR11, wherein Y represents a direct bond or —(CR7R8)pY′—, wherein p denotes a number of 0 to 3, R7 and R8 are as defined above, Y′ is selected from the group consisting of —O—, —S—, —NR12—, —NR12C(O)—, —C(O)—, —C(O)O—, —C(O)NR12—, —S(O)q—, and —S(O)qNR12—, wherein R12 represents hydrogen, alkyl, aryl or heteroaryl, q denotes a number of 0 to 2, R11 is selected from the group consisting of hydrogen, cyano, halogen, hydroxy, thiol, carboxy, alkyl and —(CH2)tB—R13, wherein t denotes a number of 0 to 3, B represents heterocycle, heteroaryl or aryl, R13 represents hydrogen, cyano, halogen, hydroxy, oxo, thiol, carboxy, carboxyalkyl, alkylcarbonyloxy, alkyl, alkoxy, alkylthio, alkylcarbonyl or alkylsulfonyl,
• R5 represents hydrogen, alkyl, cycloalkyl, heterocycle or heterocyclylalkyl,
• R6 represents —(CR7R8)p—Z-D-W—R14, wherein Z represents a direct bond, or is selected from the group consisting of —C(O)—, —C(O)O—, —C(O)NR12—, and —S(O)y—, y denotes a number of 1 or 2, D represents a direct bond, or represents cycloalkyl, heteroaryl or heterocycle, W represents a direct bond, or represents —NR7—, —C(O)—, —C(O)O—, —C(O)NR12—, —S(O)y—, —S(O)yNR12— or —NR12S(O)y—, wherein R14 represents hydrogen, hydroxy, alkyl, alkoxy, heterocycle, heteroaryl, aryl or aralkyl,
• R5 and R6 together represent alkylene chain,
• where alkyl, alkoxy, aryl, cycloalkyl, heterocycle and heteroaryl may be optionally substituted, and the substituents are one or more selected from the group consisting of hydroxy, halogen, nitrile, amino, alkylamino, dialkylamino, carboxy, alkyl, alkoxy, carboxyalkyl, alkylcarbonyloxy, alkylthio, alkyloxycarbonyl, alkylaminocarbonyl, arylalkoxy and oxo,
• provided that R3 is phenyl when X is CH, and
• provided that R6 is not hydrogen when X is C,
• and pharmaceutically acceptable salts or enantiomers or diasteromers thereof.