Indol- eller benzimidazol-derivater til modulering af IKB-kinase og mellemprodukter til fremstilling deraf

Substituted indole and benzimidazole derivatives (I), their stereoisomers and/or salts are new. Substituted indole and benzimidazole derivatives of formula (I), their stereoisomers and/or salts are new. [Image] X and M : nitrogen or CH; R1 and R11 : hydrogen, fluoro, chloro, bromo, iodo, 1-4C alkyl, cyano, trifluoromethyl, OR5, NR5R6, COR5 or S(O) xR5; x : 0-2; R5 and R6 : hydrogen or 1-4C alkyl; R2 : 3-hydroxypyrro-2,4-dione, imidazole, imidazol(id)ine, indazole, isothiazole, isothiazolidine, isoxazole, 2-isoxazolidine, isoxazolone, (thio)morpholine, oxazole, 1,3,4-oxadiazole, oxadiazolidinedione, oxadiazolone, 1,2,3,5-oxathiadiazole-2-oxide, 5-oxo-4,5-dihydro[1,3,4]oxadiazole, 5-oxo-1,2,4-thiadiazole, piperazine, pyrazine, pyrazole, pyrazoline, pyrazolidine, pyridazine, pyrimidine, tetrazole, thiadiazole, thiazole, triazole or triazolone (all optionally substituted by 1-3 of COR5, 1-4C alkyl, OR5, NR5R6, halo or keto), COR5, COOR5, or CONR7R8; R7 and R8 : hydrogen or 1-4C (hydroxy)alkyl or alkoxy; R3 : hydrogen or 1-4C alkyl; R4 : pyrrole, furan, thiophene, imidazole, pyrazole, oxazole, isoxazole, (iso)thiazole, tetrazole, 1,2,3,5-oxathiadiazole-2-oxide, triazolone, oxadiazolone, isoxazolone, oxadiazolidinedione, triazole, 3-hydroxypyrro-2,4-dione, 5-oxo-1,2,4-thiadiazole, pyridine, pyrazine, pyrimidine, (iso)indole, indazole, phthalazine, (iso)quinoline, quinoxaline, quinazoline, cinnoline, beta -carboline, all optionally benzo-fused or as cyclopenta- or cyclohexa-derivatives, or phenyl, 1- or 2-naphthyl, 2-, 3- or 4-biphenylyl, anthryl or fluorenyl, all optionally substituted by 1-3 1-5C alkyl or alkoxy, halo, nitro, amino, trifluoromethyl, hydroxy, 1-4C hydroxyalkyl, (m)ethylenedioxy, formyl, acetyl, cyano, carboxy, aminocarbonyl or 1-4C alkoxycarbonyl. An independent claim is also included for a method for preparing (I). ACTIVITY : Antiarthritic; Antirheumatic; Osteopathic; Antidiabetic; Antiinflammatory; Immunomodulator; Neuroprotective; Antiarteriosclerotic; Vasotropic; Antiulcer; Nootropic; Cytostatic; Cardiant; Antigout; Immunosuppressive; Antibacterial; Virucide; Hepatotropic; Anti-HIV; Protozoacide; Fungicide; Antiasthmatic; Antipsoriatic. MECHANISM OF ACTION : Inhibition of IkappaB kinase. The compound 2-(2-methylaminopyrimidin-4-yl)-1H-indol-5-carboxylic acid [(S)-2-diphenylamino-1-(5-oxo-4,5-dihydro[1,3,4]oxadiazol-2-yl)ethyl]amide (Ia) has IC50 against IkappaB 0.050 mu M.