4-0x0quinaz0lin-3-yl benzamide derivatives for the treatment of cytokine diseasesThe invention concerns a compound of the Formula (I) wherein m is 1-2 and each R is a group such as cyano, halogeno, trifluoromethyl heterocyclyl and heterocyclyloxy; R is trifluoromethyl or (1-6C)alkyl; R is hydrogen or halogeno; and R is isoxazolyl;or pharmaceutically-acceptable salts thereof; processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of diseases or medical condions mediated by cytokines.Formula i compound or pharmaceutically acceptable salt thereof:wherein m is 0,1 or 2;r 1be halogen, hydroxyl, cyano group, trifluoromethyl, trifluoromethoxy, c 1-6alkyl, c 1-6alkoxyl group, c 2-6thiazolinyl, c 2-6alkynyl, c 2-6alkyloyl, c 1-6alkylthio, c 1-6alkyl sulphinyl, c 1-6alkyl sulphonyl, hydroxyl-c 2-6alkoxyl group, amino-c 2-6alkoxyl group, cyano group-c 2-6alkoxyl group, c 1-6alkylamino-c 2-6alkoxyl group, two-[c 1-6alkyl] amino-c 2-6alkoxyl group, c 1-6alkoxy-c 2-6alkoxyl group, carbamyl-c 1-6alkoxyl group, n-c 1-6alkylcarbamoyl group-c 1-6alkoxyl group, amino-c 1-6alkyl, c 1-6alkylamino-c 1-6alkyl, two [c 1-6alkyl] amino-c 1-6alkyl, carbamyl-c 1-6alkyl, n-c 1-6alkylcarbamoyl group-c 1-6alkyl, hydroxyl-c 2-6alkylamino, cyano group-c 2-6alkylamino, halo-c 2-6alkylamino, amino-c 2-6alkylamino, c 1-6alkoxy-c 2-6alkylamino, c 1-6alkylamino-c 2-6alkylamino, two-[c 1-6alkyl] amino-c 2-6alkylamino, heteroaryl, heteroaryl-c 1-6alkyl, heteroaryloxy, heteroaryl-c 1-6alkoxyl group, heteroaryl amino, heterocyclic radical, heterocyclic radical-c 1-6alkyl, heterocyclic oxy group, heterocyclic radical-c 1-6alkoxyl group and heterocyclic radical amino, and r wherein 1any aryl, heteroaryl or heterocyclic radical in the substituting group can be chosen wantonly and have 1 or 2 and be selected from following substituting group: hydroxyl, halogen, c 1-6alkyl, c 2-6thiazolinyl, c 2-6alkynyl, c 3-6cycloalkyl, c 3-6cycloalkyl-c 1-6alkyl, c 3-6cycloalkyl-c 1-6alkoxyl group, c 1-6alkoxyl group, carboxyl, c 1-6carbalkoxy, c 1-6carbalkoxy-c 1-6alkyl, n-c 1-6alkylcarbamoyl group, n, n-two-[c 1-6alkyl] carbamyl, c 2-6alkyloyl, amino, c 1-6alkylamino, two-[c 1-6alkyl] amino, halo-c 1-6alkyl, hydroxyl-c 1-6alkyl, c 1-6alkoxy-c 1-6alkyl, cyano group-c 1-6alkyl, carboxyl-c 1-6alkyl, amino-c 1-6alkyl, c 1-6alkylamino-c 1-6alkyl and two-[c 1-6alkyl] amino-c 1-6alkyl, and wherein contain the ch that is connected in 2 carbon atoms 2group or be connected in the ch of 1 carbon or nitrogen-atoms 3any above-mentioned r of group 1substituting group can be chosen wantonly at each described ch 2or ch 3have one or more following substituting groups that are selected from the group: halogen, hydroxyl, amino, trifluoromethyl, trifluoromethoxy, oxo, carboxyl, carbamyl, kharophen, c 1-6alkyl, c 2-6thiazolinyl, c 2-6alkynyl, c 3-6cycloalkyl, c 3-6cycloalkyloxy, c 1-6alkoxyl group, c 1-6alkylamino, two-[c 1-6alkyl] amino, hydroxyl-c 1-6alkyl, c 1-6alkoxy-c 1-6alkyl, halo-c 1-6alkyl, c 1-6alkoxy-c 2-6alkoxyl group, c 1-6carbalkoxy, carbamyl, n-c 1-6alkylcarbamoyl group, n, n-two-[c 1-6alkyl] carbamyl, c 1-6alkyl sulphonyl, c 1-6alkylsulfamoyl group, heteroaryl, heteroaryl-c 1-6alkyl, heterocyclic radical and heterocyclic oxy group, and r wherein 1any heterocyclic radical in the substituting group can be chosen wantonly and have 1 or 2 oxo or sulfo-substituting group; r 2be halogen, trifluoromethyl or c 1-6alkyl; r 3be hydrogen, halogen or c 1-6alkyl; with r 4be different  azoles base, and r 4can choose wantonly by one or more and be selected from following substituting group and replace: halogen, hydroxyl, amino, c 1-6alkyl, c 2-6thiazolinyl, c 2-6alkynyl, c 1-6alkoxyl group, c 1-6alkylamino and two-[c 1-6alkyl] amino.
사이토킨 질환의 치료를 위한 4-옥소퀴나졸린-3-일벤즈아미드 유도체본 발명은 m이 1-2이고, 각 R1이 시아노, 할로게노, 트리플루오로메틸 헤테로시클릴 및 헤테로시클릴옥시와 같은 기이고, R2가 트리플루오로메틸 또는 (1-6C)알킬이고, R3이 수소 또는 할로게노이고, R4가 이속사졸릴인 화학식 I의 화합물 또는 그의 제약상 허용가능한 염, 그의 제조 방법, 이를 함유하는 제약 조성물, 및 사이토킨에 의해 매개되는 질환 또는 의학적 상태의 치료에서의 그의 용도에 관한 것이다.하기 화학식 I의 화합물 또는 그의 제약상 허용되는 염. <화학식 I> [이미지] 상기 식에서, m은 0, 1 또는 2이고; R1은 할로게노, 히드록시, 시아노, 트리플루오로메틸, 트리플루오로메톡시, (1-6C)알킬, (1-6C)알콕시, (2-6C)알케닐, (2-6C)알키닐, (2-6C)알카노일, (1-6C)알킬티오, (1-6C)알킬술피닐, (1-6C)알킬술포닐, 히드록시-(2-6C)알콕시, 아미노-(2-6C)알콕시, 시아노-(2-6C)알콕시, (1-6C)알킬아미노-(2-6C)알콕시, 디-[(1-6C)알킬]아미노-(2-6C)알콕시, (1-6C)알콕시-(2-6C)알콕시, 카르바모일-(1-6C)알콕시, N-(1-6C)알킬카르바모일-(1-6C)알콕시, 아미노-(1-6C)알킬, (1-6C)알킬아미노-(1-6C)알킬, 디[(1-6C)알킬]아미노-(1-6C)알킬, 카르바모일-(1-6C)알킬, N-(1-6C)알킬카르바모일-(1-6C)알킬, 히드록시-(2-6C)알킬아미노, 시아노-(2-6C)알킬아미노, 할로게노-(2-6C)알킬아미노, 아미노-(2-6C)알킬아미노, (1-6C)알콕시-(2-6C)알킬아미노, (1-6C)알킬아미노-(2-6C)알킬아미노, 디-[(1-6C)알킬]아미노-(2-6C)알킬아미노, 헤테로아릴, 헤테로아릴-(1-6C)알킬, 헤테로아릴옥시, 헤테로아릴-(1-6C)알콕시, 헤테로아릴아미노, 헤테로시클릴, 헤테로시클릴-(1-6C)알킬, 헤테로시클릴옥시, 헤테로시클릴-(1-6C)알콕시 및 헤테로시클릴아미노이고, 여기서, R1 치환체 중 임의의 아릴, 헤테로아릴 또는 헤테로시클릴기는 히드록시, 할로게노, (1-6C)알킬, (2-6C)알케닐, (2-6C)알키닐, (3-6C)시클로알킬, (3-6C)시클로알킬-(1-6C)알킬, (3-6C)시클로알킬-(1-6C)알콕시, (1-6C)알콕시, 카르복시, (1-6C)알콕시카르보닐, (1-6C)알콕시카르보닐-(1-6C)알킬, N-(1-6C)알킬카르바모일, N,N-디-[(1-6C)알킬]카르바모일, (2-6C)알카노일, 아미노, (1-6C)알킬아미노, 디-[(1-6C)알킬]아미노, 할로게노-(1-6C)알킬, 히드록시-(1-6C)알킬, (1-6C)알콕시-(1-6C)알킬, 시아노-(1-6C)알킬, 카르복시-(1-6C)알킬, 아미노-(1-6C)알킬, (1-6C)알킬아미노-(1-6C)알킬 및 디-[(1-6C)알킬]아미노-(1-6C)알킬로부터 선택된 1 또는 2개의 치환체를 임의로 함유할 수 있으며, 2개의 탄소 원자에 부착되는 CH2 기 또는 탄소 또는 질소 원자에 부착되는 CH3 기를 포함하는 상기 정의된 R1 치환체 중 임의의 것은 상기 각 CH2 또는 CH3 기 상에 할로게노, 히드록시, 아미노, 트리플루오로메틸, 트리플루오로메톡시, 옥소, 카르복시, 카르바모일, 아세트아미도, (1-6C)알킬, (2-6C)알케닐, (2-6C)알키닐, (3-6C)시클로알킬, (3-6C)시클로알콕시, (1-6C)알콕시, (1-6C)알킬아미노, 디-[(1-6C)알킬]아미노, 히드록시-(1-6C)알킬, (1-6C)알콕시-(1-6C)알킬, 할로게노-(1-6C)알킬, (1-6C)알콕시-(2-6C)알콕시, (1-6C)알콕시카르보닐, 카르바모일, N-(1-6C)알킬카르바모일, N,N-디-[(1-6C)알킬]카르바모일, (1-6C)술포닐, (1-6C)술파모일, 헤테로아릴, 헤테로아릴-(1-6C)알킬, 헤테로시클릴 및 헤테로시클릴옥시로부터 선택된 1개 이상의 치환체를 임의로 함유할 수 있으며, R1 치환체 중 임의의 헤테로시클릴기는 1 또는 2개의 옥소 또는 티옥소 치환체를 임의로 함유할 수 있고; R2는 할로게노, 트리플루오로메틸 또는 (1-6C)알킬이고; R3은 수소, 할로게노 또는 (1-6C)알킬이고; R4는 이속사졸릴이며 R4는 할로게노, 히드록시, 아미노, (1-6C)알킬, (2-6C)알케닐, (2-6C)알키닐, (1-6C)알콕시, (1-6C)알킬아미노 및 디-[(1-6C)알킬]아미노로부터 선택된 1개 이상의 치환체에 의해 임의로 치환될 수 있다.