Indole compounds as an inhibitor of cellular necrosis

A method for hepatoprotection, hepatic functional improvement, and/or treatment of hepatic disease comprising administering a composition which comprises an indole compound of the following formula (1), pharmaceutically acceptable salt or stereoisomer thereof as an active ingredient together with a pharmaceutically acceptable carrier or diluent to a subject in need thereof:

• in which
• n denotes a number of 0 to 3,
• A represents 5 membered heteroaryl or heterocycle each of which has 1 to 3 hetero atoms selected from N, O and S,
• R1 represents R5—X—B—X′—,
• B represents a direct bond, or represents 3˜10 membered heterocycle or heteroaryl each of which has 1 to 4 hetero atoms selected from N, O and S,
• X and X′ independently of one another represent a direct bond, or are selected from the group consisting of —NR6—, —CO—, —CONR6—, —CO2—, —OC(O)—, —S(O)m—, —O—(CH2)m—O—, —(CH2)m—, —NR6CO—, —(R6O)2P(O)— and —NHCO2—, wherein m denotes a number of 0 to 3, and R6 represents hydrogen or C1-C6-alkyl,
• R5 represents hydrogen, hydroxy, C1-C6-alkyl, C1-C6-alkoxy, C4-C6-cycloalkyl or phenyl, or represents 3˜10 membered monocyclic or fused cyclic heterocycle or heteroaryl each of which has 1 to 3 hetero atoms selected from N, O and S, and is optionally substituted by oxo or C1-C6-alkyl, or
• R2 represents —(CR8R9)p—Y—R7,
• p denotes a number of 0 to 2,
• R8 and R9 independently of one another represent hydrogen or C1-C6-alkyl,
• Y represents a direct bond, or is selected from the group consisting of —O—, —S—, —NR6C(O)—, —NR6C(O)—, —C(O)NR6— and —S(O)q—, wherein q denotes a number of 0 to 2,
• R7 represents hydrogen, halogen, hydroxyl, C1-C6-alkyl, phenyl or represents 3˜10 membered heterocycle or heteroaryl each of which has 1 to 3 hetero atoms selected from N, S and O and which optionally contains oxo,
• R3 represents hydrogen, C1-C6-alkyl, or —(CH2)q—C4-C6-cycloalkyl,
• R4 represents C3-C6-cycloalkyl,
• where alkyl, alkoxy, phenyl, 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, C1-C6-alkylamino, di-C1-C6-alkylamino, C1-C6-alkyl, halo-C1-C6-alkyl, C1-C6-alkylsulfonyl, carboxy-C1-C6-alkyl, C1-C6-alkylcarbonyloxy, C1-C6-alkylthio, C1-C6-alkyloxycarbonyl, C1-C6 alkylaminocarbonyl, and oxo.