AMIDE DERIVATIVES USEFUL AS INHIBITORS OF THE PRODUCTION OF CYTOKINESThe invention concerns amide derivatives of formula (I) wherein R3 is (1-6C)alkyl or halogeno; Q1 is heteroaryl which is optionally substituted with 1, 2, 3, or 4 substituents such as hydroxy, halogeno, trifluoromethyl, (1-6C)alkyl, (1-6C)alkoxy, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, hydroxy-(2-6C)alkoxy, amino-(2-6C)alkylamino, N-(1-6C)alkyl-(1-6C)alkylamino-(2-6C)alkylamino, aryl, heteroaryl and heterocyclyl; p is 0-2 and R2 is a substituent such as hydroxy and halogeno; q is 0-4; and Q2 includes optionally substituted aryl, cycloalkyl, heteroaryl and heterocyclyl; or pharmaceutically-acceptable salts or i(in vivo)-cleavable esters thereof; processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of diseases or medical conditions mediated by cytokines.An amide derivative of the Formula I wherein R3 is (l-6C)alkyl or halogeno; Q1 is heteroaryl which is optionally substituted with 1, 2, 3 or 4 substituents selected from hydroxy, halogeno, trifluoromethyl, cyano, mercapto, nitro, amino, carboxy, carbamoyl, formyl, (l-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (l-6C)alkoxy, (l-3C)alkylenedioxy, (l-6C)alkylthio, (l-6C)alkylsulphinyl, (l-6C)alkylsulphonyl, (l-6C)alkylamino, di-[(l-6C)alkyl]amino, (l-6C)alkoxycarbonyl, N-(l-6C)alkylcarbamoyl,N,N-di-[(l-6C)alkyl]carbamoyl, (2-6C)alkanoyl, (2-6C)alkanoyloxy, (l-όC)alkanoylamino, N-( 1 -6C)alkylsulphamoyl, N,N-di-[( 1 -6C)alkyl]sulphamoyl, ( 1 -6C)alkanesulphonylamino, N-( 1 -6C)alky l-( 1 -6C)alkanesulphonylamino, halogeno-( 1 -6C)alkyl, hydroxy-( 1 -6C)alkyl, (l-6C)alkoxy-(l-6C)alkyl, cyano-(l-6C)alkyl, amino-(l-6C)alkyl, (l-6C)alkylamino- (l-6C)alkyl, di-[(l-6C)alkyl]amino-(l-6C)alkyl, carboxy-(l-6C)alkyl, (l-6C)alkoxycarbonyl- ( 1 -6C)alkyl, carbamoyl-( 1 -6C)alkyl, N-( 1 -6C)alkylcarbamoyl-( 1 -6C)alkyl, N,N-di-[(l -6C)alkyl]carbamoyl-(l -6C)alkyl, halogeno-(2-6C)alkoxy, hydroxy-(2-6C)alkoxy, ( 1 -6C)alkoxy-(2-6C)alkoxy , cyano-( 1 -6C)alkoxy , carboxy-( 1 -6C)alkoxy , ( 1 -6C)alkoxycarbonyl-( 1 -6C)alkoxy , carbamoyl-( 1 -6C)alkoxy , N-( 1 -6C)alkylcarbamoyl- (l-6C)alkoxy, N,N-di-[(l-6C)alkyl]carbamoyl-(l-6C)alkoxy, amino-(2-6C)alkoxy, (l-6C)alkylamino-(2-6C)alkoxy, di-[(l-6C)alkyl]amino-(2-6C)alkoxy, halogeno- (2-6C)alkylamino, hydroxy-(2-6C)alkylamino, (l-6C)alkoxy-(2-6C)alky lamino, cyano-( 1 -6C)alkylamino, carboxy-( 1 -6C)alkylamino, ( 1 -6C)alkoxycarbonyl- (l-6C)alkylamino, carbamoyl-(l-6C)alkylamino, N-(l-6C)alkylcarbamoyl-(l-6C)alkylamino, N,N-di-[(l-6C)alkyl]carbamoyl-(l-6C)alkylamino, amino-(2-6C)alkylamino, (l-6C)alkylamino-(2-6C)alkylamino, di-[(l-6C)alkyl]amino-(2-6C)alkylamino, N-( 1 -6C)alkyl-halogeno-( 1 -6C)alky lamino, N-( 1 -6C)alkyl-hydroxy-(2-6C)alkylamino, N-( 1 -6C)alky l-( 1 -6C)alkoxy-(2-6C)alkylamino, N-( 1 -6C)alkyl-cyano-( 1 -6C)alkylamino, N-( 1 -6C)alkyl-carboxy-( 1 -6C)alkylamino, N-( 1 -6C)alkyl-( 1 -6C)alkoxycarbonyl- ( 1 -6C)alkylamino, N-( 1 -6C)alkyl-carbamoyl-( 1 -6C)alkylamino, N-( 1 -6C)alkyl- N-(l-6C)alkylcarbamoyl-(l-6C)alkylamino, N-(l-6C)alkyl-N,N-di-[(l-6C)alkyl]carbamoyl- (l-6C)alkylamino, N-(l-6C)alkyl-amino-(2-6C)alky lamino, N-(l-6C)alkyl-(l-6C)alkylamino- (2-6C)alkylamino, N-(l-6C)alkyl-di-[(l-6C)alkyl]amino-(2-6C)alkylamino, halogeno- (2-6C)alkanoylamino, hydroxy-(2-6C)alkanoylamino, ( 1 -6C)alkoxy-(2-6C)alkanoylamino, cyano-(2-6C)alkanoylamino, carboxy-(2-6C)alkanoylamino, (l-6C)alkoxycarbonyl- (2-6C)alkanoylamino, carbamoyl-(2-6C)alkanoylamino, N-(l-6C)alkylcarbamoyl- (2-6C)alkanoylamino, N,N-di-[(l -6C)alkyl]carbamoyl-(2-6C)alkanoylamino, amino-(2-6C)alkanoylamino, (l-6C)alkylamino-(2-6C)alkanoylamino, di-[(l-6C)alkyl]amino- (2-6C)alkanoylamino, aryl, aryl-(l-6C)alkyl, aryl-(l-6C)alkoxy, aryloxy, arylamino, N-( 1 -6C)alkyl-arylamino, aryl-( 1 -6C)alkylamino, N-( 1 -6C)alkyl-aryl-( 1 -6C)alkylamino, aroylamino, arylsulphonylamino, N-arylsulphamoyl, aryl-(2-6C)alkanoylamino, heteroaryl, heteroaryl-(l-6C)alkyl, heteroaryloxy, heteroaryl-(l-6C)alkoxy, heteroarylamino,N-(l -6C)alkyl-heteroarylamino, heteroaryl-(l -6C)alky lamino, N-(l -6C)alkyl-heteroaryl- (1 -6C)alkylamino, heteroarylcarbonylamino, heteroarylsulphonylamino, N-heteroarylsulphamoyl, heteroaryl-(2-6C)alkanoylamino, heterocyclyl, heterocyclyl- (l-6C)alkyl, heterocyclyloxy, heterocyclyl-(l-6C)alkoxy, heterocyclylamino, N-(l-6C)alkyl- heterocyclylamino, heterocyclyl-(l-6C)alkylamino, N-(l-6C)alkyl-heterocyclyl- ( 1 -6C)alkylamino, heterocyclylcarbonylamino, heterocyclylsulphonylamino, N-heterocyclylsulphamoyl and heterocyclyl-(2-6C)alkanoylamino, and wherein any of the substituents on Q1 defined hereinbefore which comprise a CH2 group which is attached to 2 carbon atoms or a CH3 group which is attached to a carbon atom may optionally bear on each said CH2 or CH3 group a substituent selected from hydroxy, amino, (l-6C)alkoxy, (l-6C)alkylamino, di-[(l-6C)alkyl]amino and heterocyclyl; and wherein any aryl, heteroaryl or heterocyclyl group in a substituent on Q1 may optionally bear 1 or 2 substituents selected from hydroxy, halogeno, (l-6C)alkyl, (l-6C)alkoxy, carboxy, ( 1 -6C)alkoxycarbonyl, N-( 1 -6C)alkylcarbamoyl, N,N-di-[( 1 -6C)alkyl]carbamoyl, (2-6C)alkanoyl, amino, (l-6C)alky lamino, di-[(l-6C)alkyl] amino, halogeno-(l-6C)alkyl, hydroxy-(l-6C)alkyl, (l-6C)alkoxy-(l-6C)alkyl, cyano-(l-6C)alkyl, amino-(l-6C)alkyl, (l-6C)alkylamino-(l-6C)alkyl, di-[(l-6C)alkyl]amino-(l-6C)alkyl, aryl and aryl-(l-6C)alkyl; R2 is hydroxy, halogeno, trifluoromethyl, cyano, mercapto, nitro, amino, carboxy, (l-6C)alkoxy carbonyl, (l-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (l-6C)alkoxy, (l-6C)alkylamino or di-[(l-6C)alkyl]amino; p is 0, 1 or 2; q is 0, 1, 2, 3 or 4; andQ2 is aryl, aryl-(l-6C)alkoxy, aryloxy, arylamino, N-(l-6C)alkyl-arylamino, aryl- (l-6C)alkylamino, N-(l-6C)alkyl-aryl-(l-6C)alkylamino, aroylamino, aryls...
사이토킨의 생성 억제제로서 유용한 아미드 유도체본 발명은 하기 화학식 I의 아미드 유도체, 또는 이것의 약학적으로 허용 가능한 염 또는 생체내 분해 가능한 에스테르, 이들의 제조 방법, 이들을 함유하는 약학 조성물, 그리고 시도킨을 매개로 하는 질환 또는 의학 증상의 치료 용도에 관한 것이다. 화학식 I  상기 식 중, R3은 (C1∼C6)알킬 또는 할로겐이고, Q1은 히드록시, 할로게노, 트리플루오로메틸, (C1∼C6)알킬, (C1∼C 6)알콕시, 히드록시-(C1∼C6)알킬, (C1∼C6)알콕시-(C1∼C 6)알킬, 히드록시-(C2∼C6)알콕시, 아미노(C2∼C6)알킬아미노, N-(C1∼C6)알킬-(C1∼C 6)알킬아미노-(C2∼C6)알킬아미노, 아릴, 헤테로아릴 및 헤테로시클릴과 같은 1개, 2개, 3개 또는 4개의 치환체에 의해 임의로 치환되는 헤테로아릴이며, p는 0∼2이고, R2는 히드록시 및 할로게노와 같은 치환체이며, q는 0∼4이고, Q2는 치환된 아릴, 시클로알킬 및 헤테로아릴을 임의로 포함한다.N-[5-(3-시클로헥실프로피온아미도)-2-메틸페닐]피리딘-3-카르복사미드 및 N-[5-(3-시클로헥실프로피온아미도)-2-메틸페닐]피리딘-4-카르복사미드를 제외하고, 하기 화학식 I의 아민 유도체, 또는 이것의 약학적으로 허용 가능한 염 또는 생체내 분해 가능한 에스테르: 화학식 I  R3은 (C1-C6)알킬 또는 할로게노이며, Q1은 헤테로아릴로서, 히드록시, 할로게노, 트리플루오로메틸, 시아노, 머캅토, 니트로, 아미노, 카르복시, 카르바모일, 포르밀, (C1-C6)알킬, (C2-C 6)알케닐, (C2-C6)알키닐, (C1-C6)알콕시, (C1-C3)알킬렌디옥시, (C1-C6)알킬티오, (C1-C6)알킬설피닐, (C1-C6)알킬설포닐, (C1-C6)알킬아미노, 디-[(C1 -C6)알킬]아미노, (C1-C6)알콕시카르보닐, N-(C1-C6)알킬카르바모일, N,N-디-[(C1-C6)알킬]카르바모일, (C2-C6)알카노일, (C2-C6)알카노일옥시, (C1-C6)알카노일아미노, N-(C1 -C6)알킬설파모일, N,N-디-[(C1-C6)알킬]설파모일, (C1-C6)알칸설포닐아미노, N-(C 1-C6)알킬-(C1-C6)알칸설포닐아미노, 할로게노-(C1-C6)알킬, 히드록시-(C1-C6)알킬, (C1∼C6)알콕시-(C1-C6)알킬, 시아노-(C1-C6)알킬, 아미노-(C1-C6)알킬, (C1-C 6)알킬아미노-(C1-C6)알킬, 디-[(C1-C6)알킬]아미노-(C1-C6)알킬, 카르복시-(C1-C 6)알킬, (C1-C6)알콕시카르보닐-(C1-C6)알킬, 카르바모일-(C1-C6)알킬, N-(C1-C6)알킬카르바모일-(C 1-C6)알킬, N,N-디-[(C1-C6)알킬]카르바모일-(C1-C6)알킬, 할로게노-(C2-C 6)알콕시, 히드록시-(C2-C6)알콕시, (C1-C6)알콕시-(C2-C6)알콕시, 시아노-(C1-C 6)알콕시, 카르복시-(C1-C6)알콕시, (C1-C6)알콕시카르보닐-(C1-C6)알콕시, 카르바모일-(C1 -C6)알콕시, N-(C1-C6)알킬카르바모일-(C1-C6)알콕시, N,N-디-[(C1-C6)알킬]카르바모일-(C 1-C6)알콕시, 아미노-(C2-C6)알콕시, (C1-C6)알킬아미노-(C2-C6)알콕시, 디-[(C 1-C6)알킬]아미노-(C2-C6)알콕시, 할로게노-(C2-C6)알킬아미노, 히드록시-(C2-C6)알킬아미노, (C1-C6)알콕시-(C2-C6)알킬아미노, 시아노-(C1-C6)알킬아미노, 카르복시-(C1-C6)알킬아미노, (C1-C6)알콕시카르보닐-(C1-C6)알킬아미노, 카르바모일-(C1-C6)알킬아미노, N-(C1-C6)알킬카르바모일-(C1-C6)알킬아미노, N,N-디-[(C1 -C6)알킬]카르바모일-(C1-C6)알킬아미노, 아미노-(C2-C6)알킬아미노, (C1-C6)알킬아미노-(C 2-C6)알킬아미노, 디-[(C1-C6)알킬]아미노-(C2-C6)알킬아미노, N-(C1-C 6)알킬-할로게노-(C1-C6)알킬아미노, N-(C1-C6)알킬-히드록시-(C2-C6)알킬아미노, N-(C1 -C6)알킬-(C1-C6)알콕시-(C2-C6)알킬아미노, N-(C1-C6)알킬-시아노-(C1-C6)알킬아미노, N-(C 1-C6)알킬-카르복시-(C1-C6)알킬아미노, N-(C1∼C6)알킬-(C1∼C6)알콕시카르보닐-(C 1-C6)알킬아미노, N-(C1-C6)알킬-카르바모일-(C1-C6)알킬아미노, N-(C1-C6)알킬-N-(C1 -C6)알킬카르바모일-(C1-C6)알킬아미노, N-(C1-C6)알킬-N,N-디-[(C1-C6)알킬]카르바모일-(C 1-C6)알킬아미노, N-(C1-C6)알킬-아미노-(C2-C6)알킬아미노, N-(C1-C 6)알킬-(C1-C6)알킬아미노-(C2-C6)알킬아미노, N-(C1-C6)알킬-디-[(C1-C6)알킬]아미노-(C2-C 6)알킬아미노, 할로게노-(C2-C6)알카노일아미노, 히드록시-(C2-C6)알카노일아미노, (C1-C6)알콕시-(C 2-C6)알카노일아미노, 시아노-(C2-C6)알카노일아미노, 카르복시-(C2-C6)알카노일아미노, (C1-C6)알콕시카르보닐-(C2-C6)알카노일아미노, 카르바모일-(C2-C6)알카노일아미노, N-(C1-C6)알킬카르바모일-(C2-C6)알카노일아미노, N,N-디-[(C1-C6)알킬]카르바모일-(C 2-C6)알카노일아미노, 아미노-(C2-C6)알카노일아미노, (C1-C6)알킬아미노-(C 2-C6)알카노일아미노, 디-[(C1-C6)알킬]아미노-(C2-C6)알카노일아미노, 아릴, 아릴-(C1-C6)알킬, 아릴-(C1-C6)알콕시, 아릴옥시, 아릴아미노, N-(C1-C6)알킬-아릴아미노, 아릴-(C1-C6)알킬아미노, N-(C1-C6)알킬-아릴-(C1-C6)알킬아미노, 아로일아미노, 아릴설포닐아미노, N-아릴설파모일, 아릴-(C2-C6)알카노일아미노, 헤테로아릴, 헤테로아릴-(C1 -C6)알킬, 헤테로아릴옥시, 헤테로아릴-(C1-C6)알콕시, 헤테로아릴아미노, N-(C1-C6)알킬-헤테로아릴아미노, 헤테로아릴-(C1-C6)알킬아미노, N-(C1-C6 )알킬-헤테로아릴-(C1-C6)알킬아미노, 헤테로아릴카르보닐아미노, 헤테로아릴설포닐아미노, N-헤테로아릴설파모일, 헤테로아릴-(C2-C6)알카노일아미노, 헤테로시클릴, 헤테로시클릴-(C1-C6)알킬, 헤테로시클릴옥시, 헤테로시클릴-(C1-C6)알콕시, 헤테로시클릴아미노, N-(C1-C6)알킬-헤테로시클릴아미노, 헤테로시클릴-(C1-C6)알킬아미노, N-(C1-C6)알킬-헤테로시클릴-(C1-C6)알킬아미노, 헤테로시클릴카르보닐아미노, 헤테로시클릴설포닐아미노, N-헤테로시클릴설파모일 및 헤테로시클릴-(C2-C6)알카노일아미노 중에서 선택된 1개, 2개, 3개 또는 4개의 치환체에 의해 임의로 치환되고, 여기서 2개의 탄소 원자에 결합되어 있는 CH2기 또는 1개의 탄소 원자에 결합되어 있는 CH3기를 포함하는 앞에서 정의한 Q1 상의 치환체 중 어느 하나는 히드록시, 아미노, (C1-C6)알콕시, (C1-C6)알킬아미노, 디-[(C1-C 6)알킬]아미노 및 헤테로시클릴 중에서 선택된 치환체를 상기 각 CH2기 또는 CH3기 상에 임의로 함유할 수 있으며, Q 1 상의 치환체에 있어서 임의의 아릴기, 헤테로아릴기 또는 헤테로시클릴기는 히드록시, 할로게노, (C1-C6)알킬, (C1-C6)알콕시, 카르복시, (C1 -C6)알콕시카르보닐, N-(C1-C6)알킬카르바모일, N,N-디-[(C1-C6)알킬]카르바모일, (C 2∼C6)알카노일, 아미노, (C1-C6)알킬아미노, 디-[(C1-C6)알킬]아`미노, 할로게노-(C 1-C6)알킬, 히드록시-(C1-C6)알킬, (C1-C6)알콕시-(C1-C6)알킬, 시아노-(C1-C6)알킬, 아미노-(C1-C6)알킬, (C1-C6)알킬아미노-(C1-C6)알킬, 디-[(C1-C6 )알킬]아미노-(C1-C6)알킬, 아릴 및 아릴-(C1-C6)알킬 중에서 선택된 1개 또는 2개의 치환체를 임의로 함유할 수 있고, R2는 히드록시, 할로게노, 트리플루오로메틸, 시아노, 머캅토, 니트로, 아미노, 카르복시, (C1-C6)알콕시카르보닐, (C1-C6)알킬, (C2 -C6)알케닐, (C2-C6)알키닐, (C1-C6)알콕시, (C1-C6)알킬아미노 또는 디-[(C1-C 6)알킬]아미노이며, p는 0, 1 또는 2이고, q는 0, 1, 3 또는 4이며, Q2는 아릴, 아릴-(C1-C6)알콕시, 아릴옥시, 아릴아미노, N-(C1-C 6)알킬-아릴아미노, 아릴-(C1-C6)알킬아미노, N-(C1-C6)알킬-아릴-(C1 -C6)알킬아미노, 아로일아미노, 아릴설포닐아미노, N-아릴설파모일, 아릴-(C2-C6)알카노일아미노, 시클로알킬, 헤테로아릴, 헤테로아릴옥시, 헤테로아릴-(C1-C6)알콕시, 헤테로아릴아미노, N-(C1 -C6)알킬-헤테로아릴아미노, 헤테로아릴-(C1-C6)알킬아미노, N-(C1 -C6)알킬-헤테로아릴-(C1-C6)알킬아미노, 헤테로아릴카르보닐아미노, 헤테로아릴설포닐아미노, N-헤테로아릴설파모일, 헤테로아릴-(C2-C6)알카노일아미노, 헤테로시클릴, 헤테로시클릴옥시, 헤테로시클릴-(C1-C6)알콕시, 헤테로시클릴아미노, N-(C1-C6 )알킬-헤테로시클릴아미노, 헤테로시클릴-(C1-C6)알킬아미노, N-(C1-C6)알킬-헤테로시클릴-(C 1-C6)알킬아미노, 헤테로시클릴카르보닐아미노, 헤테로시클릴설포닐아미노, N-헤테로시클릴설파모일 또는 헤테로시클릴-(C1-C6)알카노일아미노이고, Q2는 히드록시, 할로게노, 트리플루오로메틸, 시아노, 머캅토, 니트로, 아미노, 카르복시, 카르바모일, 포르밀, (C1-C6)알킬, (C2-C6)알케닐, (C2-C6)알키닐, (C1-C6)알콕시, (C1-C3)알킬렌디옥시, (C1-C6)알킬티오, (C1-C6)알킬설피닐, (C1-C 6)알킬설포닐, (C1-C6)알킬아미노, 디-[(C1-C6)알킬]아미노, (C1-C6)알콕시카르보닐, N-(C1 -C6)알킬카르바모일, N,N-디-[(C1-C6)알킬]카르바모일, (C2-C6)알카노일, (C2-C 6)알카노일옥시, (C1-C6)알카노일아미노, N-(C1-C6)알킬설파모일, N,N-디-[(C1-C6)알킬]설파모일, (C1-C6)알칸설포닐아미노, N-(C1-C6)알킬-(C1-C6)알칸설포닐아미노, 할로게노-(C1 -C6)알킬, 히드록시-(C1-C6)알킬, (C1∼C6)알콕시-(C1-C6)알킬, 시아노-(C 1-C6)알킬, 아미노-(C1-C6)알킬, (C1-C6)알킬아미노-(C1-C6)알킬, 디-[(C1-C6)알킬]아미노-(C 1-C6)알킬, 카르복시-(C1-C6)알킬, (C1-C6)알콕시카르보닐-(C1-C6)알킬, 카르바모일-(C1 -C6)알킬, N-(C1-C6)알킬카르바모일-(C1-C6)알킬, N,N-디-[(C1-C6)알킬]카르바모일-(C1 -C6)알킬, 할로게노-(C2-C6)알콕시, 히드록시-(C2-C6)알콕시, (C1-C6)알콕시-(C2-C 6)알콕시, 시아노-(C1-C6)알콕시, 카르복시-(C1-C6)알콕시, (C1-C6)알콕시카르보닐-(C1 -C6)알콕시, 카르바모일-(C1-C6)알콕시, N-(C1-C6)알킬카르바모일-(C1-C6)알콕시, N,N-디-[(C1-C6)알킬]카르바모일-(C1-C6)알콕시, 아미노-(C 2-C6)알콕시, (C1-C6)알킬아미노-(C2-C6)알콕...