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Pyridopyrazine derivatives and their use as modulators of signal transduction pathways

机译:吡咯并吡嗪衍生物及其作为信号转导途径的调节剂

摘要

Use of a compound according to the general formula (I) ** Formula ** wherein the substituents R1, R2, R3, R4 have the following meaning: R1 and R2 can independently mean: (i) hydrogen (ii) hydroxyl (iii) halogen (iv) alkyl, wherein the alkyl radical is saturated and may be composed of 1 to 8 C atoms, (v) unsubstituted or substituted aryl, wherein the aryl radical may be mono- or polysubstituted in the same or different manner with F, Cl, Br, I, CF3, CN, NH2, NH-alkyl, NH-cycloalkyl, NH-heterocyclyl, NH-aryl, NH-heteroaryl, NH-alkyl-cycloalkyl, NH- alkyl-heterocyclyl, NH-alkyl-aryl, NH-alkyl-heteroaryl, NH-alkyl-NH2, NH-alkyl-OH, N (alkyl) 2, NHC (O) -alkyl, NHC (O) -cycloalkyl, NHC ( O) -heterocyclyl, NHC (O) -aryl, NHC (O) -heteroaryl, NHC (O) -alkyl-aryl, NHC (O) -alkyl-heteroaryl, NHSO2-alkyl, NHSO2-cycloalkyl, NHSO2-heterocyclyl, NHSO2 -aryl, NHSO2-heteroaryl, NHSO2-alkyl-aryl, NHSO2-alkyl-heteroaryl, NO2 , SH, S-alkyl, S-aryl, S-heteroaryl, OH, OCF3, O-alkyl, O-cycloalkyl, O-heterocyclyl, O-aryl, O-heteroaryl, O-alkyl-cycloalkyl, O-alkyl-heterocyclyl , O-alkyl-aryl, O-alkyl-heteroaryl, O-alkyl-OH, O- (CH2) nO, OC (O) -alkyl, OC (O) -cycloalkyl, OC (O) -heterocyclyl, OC (O ) -aryl, OC (O) -heteroaryl, OC (O) -alkyl-aryl, OC (O) -alkyl-heteroaryl, OSO3H, OSO2-alkyl, OSO2-cycloalkyl, OSO2-heterocyclyl, OSO2-aryl, OSO2-heteroaryl , OSO2-alkyl-aryl, OSO2-alkyl-heteroaryl, OP (O) (OH) 2, C (O) -alkyl, C (O) -aryl, C (O) -heteroaryl, CO2H, CO2-alkyl, CO2 -cycloalkyl, CO2-heterocyclyl, CO2-aryl, CO2-heteroaryl, CO2- alkyl-cycloalkyl, CO2-alkyl-heterocyclyl, CO2-alkyl-aryl, CO2-alkyl-heteroaryl, C (O) -NH2, C (O) NH-alkyl, C (O) NH-cycloalkyl, C (O) NH-heterocyclyl, C (O) NH-aryl, C (O) NH-heteroaryl, C (O) NH-alkyl-cycloalkyl, C (O) NH-alkyl-heterocyclyl, C (O) NH-alkyl-aryl, C (O) NH-alkyl-heteroaryl, C (O) N (alkyl) 2, C (O) N (cycloalkyl) 2, C (O) N (aryl) 2, C (O) N (heteroaryl) 2, SO-alkyl, SO-aryl, SO2-alkyl, SO2-aryl, SO2NH2, SO2NH-alkyl, SO2NH-aryl, SO2NH-heteroaryl, SO2NH-alkyl-aryl, SO3H, SO2O-alkyl , SO2O-aryl, SO2O-alkyl-aryl, alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, n may take the value 1, 2 or 3, and the substituents of alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, alkyl-cycloalkyl, alkyl-heterocyclyl, alkyl-aryl and alkyl-heteroaryl may, in turn, be substituted, (vi) unsubstituted or substituted heteroaryl, wherein the heteroaryl radical may be mono- or polysubstituted equally or differently with F, Cl, Br, I, CF3, CN, NH2, NH-alkyl, NH-cycloalkyl, NH-heterocyclyl, NH-aryl, NH-heteroaryl, NH-alkyl-cycloalkyl, NH-alkyl-heterocyclyl, NH-alkyl-aryl, NH- alkyl-heteroaryl, NH-alkyl-NH2, NH-alkyl-OH, N (alkyl) 2, NHC (O) -alkyl, NHC (O) -cycloalkyl, NHC (O) -heterocyclyl, NHC (O) -aryl, NHC (O) -heteroaryl, NHC (O) -alkyl-aryl, NHC (O) -alkyl-heteroaryl, NHSO2-alkyl, NHSO2-cycloalkyl, NHSO2-heterocyclyl, NHSO2-aryl, NHSO2-heteroaryl, NHSO2-alkyl-aryl, NHSO2-alkyl-heteroaryl, NO2, SH, S-alkyl, S-aryl, S-heteroaryl, OH, OCF3, O-alkyl, O-cycloalkyl, O-aryl, O-heteroaryl, O-alkyl-cycloalkyl, O-alkyl-heterocyclyl, O-alkyl-aryl, O-alkyl-heteroaryl, OC (O) - alkyl, OC (O) -cycloalkyl, OC (O) -heterocyclyl, OC (O) -aryl, OC (O) -heteroaryl, OC (O) -alkyl-aryl, OC (O) - alkyl-heteroaryl, OSO3H, OSO2-alkyl , OSO2-cycloalkyl, OSO2-heterocyclyl, OSO2-aryl, OSO2-heteroaryl, OSO2-alkyl-aryl, OSO2-alkyl-heteroaryl, OP (O) (OH) 2, C (O) -alkyl, C (O) - aryl, C (O) - heteroaryl, CO2H, CO2-alkyl, CO2-cycloalkyl, CO2-heterocyclyl, CO2-aryl, CO2-heteroaryl, CO2-alkyl-cycloalkyl, CO2-alkyl-heterocyclyl, CO2-alkyl-aryl, CO2 -alkyl-heteroaryl, C (O) -NH2, C (O) NH-alkyl, C (O) NH-cycloalkyl, C (O) NH-heterocyclyl, C (O) NH-aryl, C (O) NH- heteroaryl, C (O) NH-alkyl-cycloalkyl, C (O) NH-alkyl-heterocyclyl, C (O) NH-a alkyl-aryl, C (O) NH-alkyl-heteroaryl, C (O) N (alkyl) 2, C (O) N (cycloalkyl) 2, C (O) N (aryl) 2, C (O) N ( heteroaryl) 2, SO2NH2, SO2NH-alkyl, SO2NH-aryl, SO2NH-heteroaryl, SO2NH-alkyl-aryl, SO3H, SO2O-alkyl, SO2O-aryl, SO2O-alkyl-aryl, alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, and the substituents of alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl may, in turn, be substituted, (vii) OR5, wherein R5 may be alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, alkyl-cycloalkyl, alkyl-heterocyclyl, alkyl-aryl or alkyl-heteroaryl, and the substituents of alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, alkyl-cycloalkyl, alkyl-heterocyclyl, alkyl-aryl or alkyl-heteroaryl may, in turn, be substituted, (viii) SR6 , wherein R 6 may be alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, alkyl-cycloalkyl, alkyl-heterocyclyl, alkyl-aryl or alkyl-heteroaryl, and the substituents of alkyl, cycloalkyl, h Eterocyclyl, aryl and heteroaryl, alkyl-cycloalkyl, alkyl-heterocyclyl, alkyl-aryl or alkyl-heteroaryl can be, in turn, substituted, ix) NR7R8, where R7 and R8 can be, independently of each other, hydrogen, alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, alkyl-cycloalkyl, alkyl-heterocyclyl, alkyl-aryl or alkyl-heteroaryl, and the substituents of alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, alkyl-cycloalkyl, alkyl-heterocyclyl, alkyl- aryl or alkyl-heteroaryl may be substituted in turn, or R7 and R8 together mean heterocyclyl, wherein heterocyclyl can be substituted.
机译:根据通式(I)**式**的化合物的用途,其中取代基R1,R2,R3,R4具有以下含义:R1和R2可以独立地表示:(i)氢(ii)羟基(iii) (v)烷基,其中烷基是饱和的并且可以由1至8个C原子组成;(v)未取代或取代的芳基,其中芳基可以与F相同或不同的方式被单取代或多取代, Cl,Br,I,CF 3,CN,NH 2,NH-烷基,NH-环烷基,NH-杂环基,NH-芳基,NH-杂芳基,NH-烷基-环烷基,NH-烷基-杂环基,NH-烷基-芳基, NH-烷基-杂芳基,NH-烷基-NH2,NH-烷基-OH,N(烷基)2,NHC(O)-烷基,NHC(O)-环烷基,NHC(O)-杂环基,NHC(O)-芳基,NHC(O)-杂芳基,NHC(O)-烷基-芳基,NHC(O)-烷基-杂芳基,NHSO2-烷基,NHSO2-环烷基,NHSO2-杂环基,NHSO2--芳基,NHSO2-杂芳基,NHSO2-烷基-芳基,NHSO 2-烷基-杂芳基,NO 2,SH,S-烷基,S-芳基,S-杂芳基,OH,OCF 3,O-烷基,O-环烷基,O-杂杂环基,O-芳基,O-杂芳基,O-烷基-环烷基,O-烷基-杂环基,O-烷基-芳基,O-烷基-杂芳基,O-烷基-OH,O-(CH2)nO,OC(O )-烷基,OC(O)-环烷基,OC(O)-杂环基,OC(O)-芳基,OC(O)-杂芳基,OC(O)-烷基芳基,OC(O)-烷基-杂芳基, OSO3H,OSO2-烷基,OSO2-环烷基,OSO2-杂环基,OSO2-芳基,OSO2-杂芳基,OSO2-烷基-芳基,OSO2-烷基-杂芳基,OP(O)(OH)2,C(O)-烷基, C(O)-芳基,C(O)-杂芳基,CO 2 H,CO 2-烷基,CO 2-环烷基,CO 2-杂环基,CO 2-芳基,CO 2-杂芳基,CO 2-烷基-环烷基,CO 2-烷基-杂环基,CO 2-烷基-芳基,CO2-烷基-杂芳基,C(O)-NH2,C(O)NH-烷基,C(O)NH-环烷基,C(O)NH-杂环基,C(O)NH-芳基,C (O)NH-杂芳基,C(O)NH-烷基-杂环基,C(O)NH-烷基-杂环基,C(O)NH-烷基-芳基,C(O)NH-烷基-杂芳基,C(O )N(烷基)2,C(O)N(环烷基)2,C(O)N(芳基)2,C(O)N(杂芳基)2,SO-烷基,SO-芳基,SO2-烷基,SO2 -芳基,SO2NH2,SO2NH-烷基,SO2NH-芳基,SO2NH-杂芳基,SO 2 NH-烷基-芳基,SO 3 H,SO 2 O-烷基,SO 2 O-芳基,SO 2 O-烷基-芳基,烷基,环烷基,杂环基,芳基或杂芳基,n可以取值为1、2或3,并且烷基的取代基环烷基,杂环基,芳基,杂芳基,烷基-环烷基,烷基-杂环基,烷基-芳基和烷基-杂芳基又可以被取代,(vi)未取代或取代的杂芳基,其中杂芳基可以是单取代或多取代的与F,Cl,Br,I,CF3,CN,NH2,NH-烷基,NH-环烷基,NH-杂环基,NH-芳基,NH-杂芳基,NH-烷基-环烷基,NH-烷基-杂环基相同或不同NH-烷基-芳基,NH-烷基-杂芳基,NH-烷基-NH2,NH-烷基-OH,N(烷基)2,NHC(O)-烷基,NHC(O)-环烷基,NHC(O)-杂环基,NHC(O)-芳基,NHC(O)-杂芳基,NHC(O)-烷基芳基,NHC(O)-烷基-杂芳基,NHSO2-烷基,NHSO2-环烷基,NHSO2-杂环基,NHSO2-芳基,NHSO2 -杂芳基,NHSO2-烷基-芳基,NHSO2-烷基-杂芳基,NO2,SH,S-烷基,S-芳基,S-杂芳基,OH,OCF3, O-烷基,O-环烷基,O-芳基,O-杂芳基,O-烷基-环烷基,O-烷基-杂环基,O-烷基-芳基,O-烷基-杂芳基,OC(O)-烷基,OC(O )-环烷基,OC(O)-杂环基,OC(O)-芳基,OC(O)-杂芳基,OC(O)-烷基芳基,OC(O)-烷基-杂芳基,OSO3H,OSO2-烷基,OSO2 -环烷基,OSO2-杂环基,OSO2-芳基,OSO2-杂芳基,OSO2-烷基-芳基,OSO2-烷基-杂芳基,OP(O)(OH)2,C(O)-烷基,C(O)-芳基, C(O)-杂芳基,CO2H,CO2-烷基,CO2-环烷基,CO2-杂环基,CO2-芳基,CO2-杂芳基,CO2-烷基-环烷基,CO2-烷基-杂环基,CO2-烷基-芳基,CO2-烷基-杂芳基,C(O)-NH 2,C(O)NH-烷基,C(O)NH-环烷基,C(O)NH-杂环基,C(O)NH-芳基,C(O)NH-杂芳基, C(O)NH-烷基-环烷基,C(O)NH-烷基-杂环基,C(O)NH-a烷基-芳基,C(O)NH-烷基-杂芳基,C(O)N(烷基)2 ,C(O)N(环烷基)2,C(O)N(芳基)2,C(O)N(杂芳基)2,SO2NH2,SO2NH-烷基,SO2NH-芳基,SO2NH-杂芳基,SO2NH-烷基-芳基,SO3H,SO2O-烷基,SO 2O-芳基,SO 2 O-烷基-芳基,烷基,环烷基,杂环基,芳基或杂芳基,以及烷基,环烷基,杂环基,芳基和杂芳基的取代基可依次被取代,(vii)OR5,其中R5可为烷基,环烷基,杂环基,芳基,杂芳基,烷基-环烷基,烷基-杂环基,烷基-芳基或烷基-杂芳基,以及烷基,环烷基,杂环基,芳基,杂芳基,烷基-环烷基,烷基-杂环基,烷基- (viii)SR 6可以依次被芳基或烷基-杂芳基取代,其中R 6可以是烷基,环烷基,杂环基,芳基,杂芳基,烷基-环烷基,烷基-杂环基,烷基-芳基或烷基-杂芳基,和烷基,环烷基,h杂环基,芳基和杂芳基,烷基-环烷基,烷基-杂环基,烷基-芳基或烷基-杂芳基的取代基可以依次被取代:ix)NR7R8,其中R7和R8可以独立于氢,烷基,环烷基,杂环基,芳基,杂芳基,烷基-环烷基,烷基-杂环基,烷基-芳基或烷基-杂芳基,以及烷基,环烷基,杂环基,芳基和杂芳基,烷基-环烷基,烷基-杂环基,烷基-芳基或烷基-杂芳基的取代基可以依次被取代,或R7 R 8和R 8一起表示杂环基,其中杂环基可以被取代。

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