INDOLE AMIDE COMPOUND AS INHIBITOR OF NECROSIS

摘要

The present invention relates to an indole amide compound represented by formula (1), a pharmaceutically acceptable salt or isomer thereof, a composition for prevention or treatment of necrosis and necrosis-associated diseases, and a method for preparing the composition, the composition comprising the indole compound or the pharmaceutically acceptable salt or isomer thereof as an active ingredient.

主权项

1. An indole amide compound of the following Formula (1) or a pharmaceutically acceptable salt or isomer thereof: in which R1 represents hydrogen, C1-C6-alkyl or —(CH2)n—C3-C8-cycloalkyl; n denotes a number of 0 to 2; R2 represents —X—(CH2)n-A-R6, wherein X represents a direct bond or —C(O)—, A represents a direct bond, or represents C3-C8-cycloalkyl or C6-C10 aryl, or represents 4- to 8-membered heterocyclyl or heteroaryl each of which has 1 to 3 heteroatoms selected from N, O and S, R6 represents hydrogen, C1-C6-alkyl, halogen, hydroxy, amino, nitrile, nitro or —CO2—R7, and R7 represents hydrogen, C1-C6-alkyl, C6-C10 aryl or C6-C10 aryl-C1-C6-alkyl, or represents 5- or 6-membered heterocyclyl or heteroaryl each of which optionally contains oxo, and has 1 to 3 heteroatoms selected from N, O and S; R1 and R2 may together represent —(CH2)r- wherein r denotes a number of 4 to 6; R3 represents hydrogen, halogen, hydroxy, —O—R7, —NH—R7 or —(CH2)m—R7, wherein m denotes a number of 0 to 3; R4 represents —(CHR7)n-B—(Z—R8)(Z′—R9), wherein B represents a direct bond, or represents C6-C10 aryl, or represents 4- to 9-membered heterocyclyl or heteroaryl each of which has 1 to 3 heteroatoms selected from N, O and S, Z and Z′ independently of one another represent a direct bond, —(CH2)m—, —O— or —N—, and R8 and R9 independently of one another represent hydrogen, halogen, hydroxy, amino, di(C1-C6-alkyl)amino, C1-C6-alkyl, —CO2R7, C3-C8-cycloalkyl, C6-C10-aryl, C6-C10-aryloxy, C6-C10-aryl-C1-C6-alkyl or C6-C10-aryl-C1-C6-alkylamino, or represents 4- to 8-membered heterocyclyl which has 1 to 3 heteroatoms selected from N, O and S; R5 represents —(CH2)m—R10, wherein R10 represents hydrogen, C1-C6-alkyl or C6-C10-aryl; Z′ and R5 may be connected with an atom(s) to which they are attached to form the structure provided that when Z′ is —O—, R9 does not exist; 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, arylalkoxy and oxo.