Use of a composition comprising a TRAIL protein and an indole or benzimidazole derivative to prepare a medicament for treating pain

摘要

Composition comprising a TRAIL protein with a specified amino acid sequence (not given in the specification) or a TRAIL derivative, an indole or benzimidazole derivative (I) and a carrier is used to prepare a medicament for treating pain. Composition comprising a TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) protein with a specified amino acid sequence (not given in the specification) or a TRAIL derivative, an indole or benzimidazole derivative (I) and a carrier is used to prepare a medicament for treating pain. E : N, CH or CR9>; R1>-R4>D-NR8>-CHR9>-Z, H, halo, 1-6C alkyl, Het', NO2, CN, aryl(0-4C)alkoxy, 1-4C alkoxy, OR11>, N(R11>)2, SOrR11> or CF3, provided that one is D-NR8>-CHR9>-Z; r : 0-2; Het' : 5- to 14-membered heteroaryl or 5- to 12-membered heterocyclyl, each with 0-3 substituents; D : CO, SO or SO2; R8>H or 1-4C alkyl; R9>an amino acid residue, optionally substituted aryl, Het', or 1-5C alkyl optionally substituted with 1-3 of Ar', Het', OR11>, oxo, halo, CN, CF3, SOrR11>, COOR11>, CON(R11>)2, COR11>, N(R11>)2, 3-6C cycloalkyl, CR11>=C(R11>)2 or CCR11>; Ar' : optionally substituted aryl; R11>H, 1-6C alkyl (optionally substituted with 1-3 of Ar', Het', hetrocycloalkyl with 5-12 ring members, halo, NH2, mono- or di(1-6C alkyl)amino (optionally substituted with halo or COOH), 1-6C alkoxy or COOH), Ar' or Het'; Z : Ar, Het', optionally substituted 1-6C alkyl, COR11>, COOR11> or CON(R11>)2; R8>+R9>A-X-Y-B optionally substituted with 1-3 of Q; A : N or CH2; B, X : O, S, N or CH2; Y : a bond, O, S, N or CH2; X+Y : phenyl, 1,2-diazine, 1,3-diazine or 1,4-diazine; Q : 1-8C alkyl optionally substituted with 1-2 of Q'; Q' : OH, 1-8C alkoxy, halo, NO2, NH2, CF3, methylenedioxy, -C(O) (sic), COMe, 1-4C alkoxycarbonyl, CN, COOH, CONH2, tetrazolyl, phenyl, phenoxy, benzyl or benzyloxy; R9>+Z : T-V-W-NR11>-CO optionally substituted with 1-3 of Q'; T, W : O, S, N or CH2; V : a bond, O, S, N or CH2; T+V or V+W : phenyl, 1,2-diazine, 1,3-diazine or 1,4-diazine; R5>H, OH or oxo; R6>Ar; phenyl substituted with 1-2 of CN, NO2, 1-4C alkoxy, N(R11>)2, NHCOR11>, SOrR11>, COR11> or 1-4C aminoalkyl; or Het'. [Image] ACTIVITY : Analgesic; Cytostatic; Anti-HIV. MECHANISM OF ACTION : Tumor necrosis factor ligand; IkappaB kinase inhibitor.