New aryl amide compounds are kinase inhibitors useful for the treatment and/or prophylaxis of e.g. tumors, psoriasis, rheumatoid arthritis, contact dermatitis, inflammations, endometriosis, scar and benign prostatic hyperplasia

摘要

Aryl amide compounds (I) and their salts, derivatives, solvates and/or stereoisomers including their mixtures in all ratios are new. Aryl amide compounds (I) of formula (Ar 1-N(R 2)-CH(=Y)-Ar 2-Z-Ar 3) and their salts, derivatives, solvates and/or stereoisomers including their mixtures in all ratios are new. Ar 1-Ar 3aromatic (optionally substituted with R 1) or Het; Het : 1-2 aromatic heterocyclic ring with 1-4 N-, O- and/or S-; R 1H, A, aryl, OR 4, SR 4, Oaryl, Saryl, N(R 4) 2, NHaryl, Hal, NO 2, CN, (CH 2) mCOOR 4, (CH 2) mCOOaryl, (CH 2) mCON(R 4) 2, (CH 2) mCONHaryl, COR 4, COaryl, S(O) mA, S(O) maryl, NHCOA, NHCOaryl, NHSO 2A, NHSO 2aryl, SO 2N(R 4) 2, O(CH 2) n, N(R 4) 2, O(CH 2) nNHR 3, O(CH 2) n-oxo-piperazine, O(CH 2) n-oxomorpholine, O(CH 2) n-oxopyrrolidine, O(CH 2) nC(CH 2) 2(CH 2) nN(R 4) 2, N(CH 2) nC(CH 3) 2(CH 2) nN(R 4) 2, O(CH 2) nN(R 4)SO mA, O(CH 2) nN(R 4)SO mN(R 4)A, O(CH 2) nN(R 4)SO maryl, (CH 2) nN(R 4)SO mA, (CH 2) nN(R 4)SO mN(R 4)A, (CH 2) nN(R 4)SO maryl, O(CH 2) nSO mA, O(CH 2) nSO mN(R 4)A, O(CH 2) nSO maryl, (CH 2) nSO mA, (CH 2) nSO mN(R 4)A and/or (CH 2) nSO maryl; Y : O, S, C-NO-2, C(CN) 2 or N-R 3; Z : G 1 n, G 1 nEG 2 m, EG 1 nG 2 m or G 1 nG 2 mE; R 2-R 4H, A or -alkylene-aryl; A : 1-10C alkyl (where 1-2 CH 2- group is replaced with O-, S and/or with -CH=CH- and/or 1-7H atom is replaced with Hal), aryl (optionally substituted with A), phenyl, OA, SA, Ophenyl, NH 2, NA 2, hal, NO 2, CN, (CH 2) mCOOR 4, (CH 2) mCON(R 4) 2, COR 4, COaryl, S(O) mA, NHCOA or NHSO 2A substituted phenyl; E : O, SO m, NR 1, CO, C=N or alkene; G 1, G 2CR 1R 1 or E; Hal : F, Cl, Br or I; n : 0-5; and m : 0-2. Independent claims are also included for: (1) the preparation of (I); (2) medicament comprising (I), carriers and/or adjuvants and optionally at least additional drug active agents; (3) a set (kit) comprising divided packings of (I) and additional drug active agents; and (4) use of (I) in combination with radiotherapy and a compound (estrogen receptor modulators, androgen receptor modulators, retinoid receptor modulators, cytotoxic drug, antiproliferative agents, prenyl-proteintransferase inhibitors, 3-hydroxy 3-methyl glutaryl coenzyme A reductase inhibitors, HIV-protease inhibitors, reverse transcriptase inhibitors, growth factor receptor inhibitors and angiogenesis inhibitors) for preparing medicaments for the treatment and/or prophylaxis of diseases. ACTIVITY : Antiangiogenic; Cytostatic; Antidiabetic; Ophthalmological; Osteopathic; Antiarthritic; Antipsoriatic; Antirheumatic; Antiinflammatory; Dermatological; Gynecological; Vulnerary; Immunostimulant; Immunosuppressive. MECHANISM OF ACTION : Kinase activator; Kinase inhibitor; Tyrosine kinase inhibitor; Raf-kinase inhibitor. The ability of (I) to inhibit tyrosine kinase activity using biological assays. The results showed that (I) inhibited vascular endothelial growth factor stimulated mitogenesis in a culture containing human endothelial cells at HK-50 value of 0.01-5 microM.