Novel pyridopyrazines and their use as modulators of kinases

Abstract

The invention relates to novel pyrido[2,3-b]pyrazine derivatives of the general formulae (I) and (II), and to their preparation and use as medicaments, especially for the treatment of malignant disorders and other disorders based on pathological cell proliferations.

1 - 64 . (canceled) 
     
     
         65 . A pyrido[2,3-b]pyrazine compound of the Formula I 
       
         
           
           
               
               
           
         
         wherein: 
         R2 and R4: hydrogen 
         R1 is substituted heteroaryl, wherein the heteroaryl has one or more, identical or different, substituents selected from the group consisting of
 (i) NH-alkyl, NH-cycloalkyl, NH-heterocyclyl, NH-aryl, NH-heteroaryl, NH-alkyl-cycloalkyl, NH-alkyl-heterocyclyl, NH-alkyl-aryl, NH-alkyl-heteroaryl, NH-alkyl-NH 2 , 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, NHSO 2 -alkyl, NHSO 2 -cycloalkyl, NHSO 2 -heterocyclyl, NHSO 2 -aryl, NHSO 2 -heteroaryl, NHSO 2 -alkyl-aryl, NHSO 2 -alkyl-heteroaryl, S-alkyl, S-aryl, S-heteroaryl, 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, OSO 2 -alkyl, OSO 2 -cycloalkyl, OSO 2 -heterocyclyl, OSO 2 -aryl, OSO 2 -heteroaryl, OSO 2 -alkyl-aryl, OSO 2 -alkyl-heteroaryl, C(O)-alkyl, C(O)-aryl, C(O)-heteroaryl, CO 2 -alkyl, CO 2 -cycloalkyl, CO 2 -heterocyclyl, CO 2 -aryl, CO 2 -heteroaryl, CO 2 -alkyl-cycloalkyl, CO 2 -alkyl-heterocyclyl, CO 2 -alkyl-aryl, CO 2 -alkyl-heteroaryl, 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 2 NH-alkyl, SO 2 NH-aryl, SO 2 NH-heteroaryl, SO 2 NH-alkyl-aryl, SO 2 O-alkyl, SO 2 O-aryl, SO 2 O-alkyl-aryl, alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl,
 wherein the alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl substituents of (i) optionally include one or more, identical or different, substituents selected from the group consisting of
 (ii) NH-cycloalkyl, NH-heterocyclyl, NH-heteroaryl, NH-alkyl-cycloalkyl, NH-alkyl-heterocyclyl, NH-alkyl-aryl, NH-alkyl-heteroaryl, NH-alkyl-NH 2 , NH-alkyl-OH, NHC(O)-alkyl, NHC(O)-cycloalkyl, NHC(O)-heterocyclyl, NHC(O)-aryl, NHC(O)-heteroaryl, NHC(O)-alkyl-aryl, NHC(O)-alkyl-heteroaryl, NHSO 2 -alkyl, NHSO 2 -cycloalkyl, NHSO 2 -heterocyclyl, NHSO 2 -aryl, NHSO 2 -heteroaryl, NHSO 2 -alkyl-aryl, NHSO 2 -alkyl-heteroaryl, S-aryl, S-heteroaryl, O-cycloalkyl, 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, OSO 2 -alkyl, OSO 2 -cycloalkyl, OSO 2 -heterocyclyl, OSO 2 -aryl, OSO 2 -heteroaryl, OSO 2 -alkyl-aryl, OSO 2 -alkyl-heteroaryl, C(O)-alkyl, C(O)-aryl, C(O)-heteroaryl, CO 2 -alkyl, CO 2 -cycloalkyl, CO 2 -heterocyclyl, CO 2 -aryl, CO 2 -heteroaryl, CO 2 -alkyl-cycloalkyl, CO 2 -alkyl-heterocyclyl, CO 2 -alkyl-aryl, CO 2 -alkyl-heteroaryl, C(O)—NH 2 , 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 2 NH 2 , SO 2 NH-alkyl, SO 2 NH-aryl, SO 2 NH-heteroaryl, SO 2 NH-alkyl-aryl, SO 2 O-alkyl, SO 2 O-aryl, SO 2 O-alkyl-aryl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, 
 wherein the alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl of (ii) optionally include one or more, same or different, substituents selected from the group consisting of 
  (iii) H, F, Cl, Br, I, CF 3 , CHF 2 , CN, NH 2 , NH-alkyl, N(alkyl) 2 , NO 2 , SH, S-alkyl, OH, OCF 3 , OCHF 2 , O-alkyl, alkyl, alkyl-O—[(CH 2 ) n —O] m  (n=1, 2 or 3, m=1, 2 or 3), CH(O), C(O)-alkyl, CO 2 H, CO 2 -alkyl, C(O)—NH 2 , C(O)NH-alkyl, C(O)N(alkyl) 2 , SO 3 H, SO 2 -alkyl, SO 2 NH 2 , SO 2 NH-alkyl, and SO 2 N(alkyl) 2 , 
 
 
 
         R3 is NR9R10, wherein R9 is
 (iv) hydrogen, alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, alkyl-cycloalkyl, alkyl-heterocyclyl, alkyl-aryl or alkyl-heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl optionally include one or more, same or different, substituents selected from the group consisting of 
 (v) H, F, Cl, Br, I, CF 3 , CHF 2 , CN, NH 2 , NH-alkyl, N(alkyl) 2 , NO 2 , SH, S-alkyl, OH, OCF 3 , OCHF 2 , O alkyl, alkyl, alkyl-O—[(CH 2 ) n —O] m  (n=1, 2 or 3, m=1, 2 or 3), CH(O), C(O)-alkyl, CO 2 H, CO 2 -alkyl, C(O)—NH 2 , C(O)NH-alkyl, C(O)N(alkyl) 2 , SO 3 H, SO 2 NH 2 , SO 2 NH-alkyl, and SO 2 N(alkyl) 2 , 
 
         R10 is —C(Y)NR11R12, where Y is O or S, wherein R11 and R12 are independently of one another
 (vi) hydrogen, 
 (vii) unsubstituted or substituted alkyl, where the alkyl radical optionally includes one or more, identical or different, substituents selected from the group consisting of F, Cl, Br, I, CF 3 , CN, NH 2 , NH-alkyl, NH-cycloalkyl, NH-heterocyclyl, NH-aryl, NH-heteroaryl, NH-alkyl-cycloalkyl, NH-alkyl-heterocyclyl, NH-alkyl-aryl, NH-alkyl-heteroaryl, N(alkyl) 2 , NHC(O)-alkyl, NHC(O)-cycloalkyl, NHC(O)-heterocyclyl, NHC(O)-aryl, NHC(O)-hetero-aryl, NHC(O)-alkyl-aryl, NHC(O)-alkyl-heteroaryl, NHSO 2 -alkyl, NHSO 2 -cycloalkyl, NHSO 2 -heterocyclyl, NHSO 2 -aryl, NHSO 2 -heteroaryl, NHSO 2 -alkyl-aryl, NHSO 2 -alkyl-heteroaryl, NO 2 , SH, S-alkyl, S-cycloalkyl, S-heterocyclyl, S-aryl, S-heteroaryl, OH, OCF 3 , O-alkyl, O-cycloalkyl, O-heterocyclyl, 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, OSO 3 H, OSO 2 -alkyl, OSO 2 -cycloalkyl, OSO 2 -heterocyclyl, OSO 2 -aryl, OSO 2 -heteroaryl, OSO 2 -alkyl-aryl, OSO 2 -alkyl-heteroaryl, OP(O)(OH) 2 , C(O)-alkyl, C(O)-aryl, C(O)-heteroaryl, CO 2 H, CO 2 -alkyl, CO 2 -cycloalkyl, CO 2 -heterocyclyl, CO 2 -aryl, CO 2 -heteroaryl, CO 2 -alkyl-cycloalkyl, CO 2 -alkyl-heterocyclyl, CO 2 -alkyl-aryl, CO 2 -alkyl-heteroaryl, C(O)—NH 2 , 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, SO 2 -alkyl, SO 2 -aryl, SO 2 NH 2 , SO 2 NH-alkyl, SO 2 NH-aryl, SO 2 NH-heteroaryl, SO 2 NH-alkyl-aryl, SO 3 H, SO 2 O-alkyl, SO 2 O-aryl, SO 2 O-alkyl-aryl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, 
 (viii) unsubstituted or substituted cycloalkyl, where the cycloalkyl radical optionally includes one or more, identical or different, substituents selected from the group consisting of F, Cl, Br, I, NH 2 , NH-alkyl, NH-cycloalkyl, NH-heterocyclyl, NH-aryl, NH-heteroaryl, NH-alkyl-aryl, NH-alkyl-heteroaryl, 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, NHSO 2 -alkyl, NHSO 2 -cycloalkyl, NHSO 2 -heterocyclyl, NHSO 2 -aryl, NHSO 2 -heteroaryl, NHSO 2 -alkyl-aryl, NHSO 2 -alkyl-heteroaryl, OH, O-alkyl, O-cycloalkyl, O-heterocyclyl, O-aryl, O-heteroaryl, 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, OSO 3 H, OSO 2 -alkyl, OSO 2 -cycloalkyl, OSO 2 -heterocyclyl, OSO 2 -aryl, OSO 2 -heteroaryl, OSO 2 -alkyl-aryl, OSO 2 -alkyl-heteroaryl, OP(O)(OH) 2 , CO 2 H, CO 2 -alkyl, CO 2 -cycloalkyl, CO 2 -heterocyclyl, CO 2 -aryl, CO 2 -heteroaryl, CO 2 -alkylcycloalkyl, CO 2 -alkyl-hetero-cyclyl, CO 2 -alkyl-aryl, CO 2 -alkyl-heteroaryl, C(O)—NH 2 , C(O)NH-aryl, 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 , alkyl, and aryl, 
 (ix) unsubstituted or substituted heterocyclyl, wherein the heterocyclyl radical optionally includes one or more, identical or different, substituents selected from the group consisting of OH, O-alkyl, O-aryl, NH 2 , NH-alkyl, NH-aryl, alkyl, alkyl-aryl, and aryl, 
 (x) unsubstituted or substituted aryl, wherein the aryl radical optionally includes one or more, identical or different, substituents selected from the group consisting of F, Cl, Br, I, CF 3 , CN, NH 2 , NH-alkyl, NH-cycloalkyl, NH-heterocyclyl, NH-aryl, NH-heteroaryl, NH-alkyl-cycloalkyl, NH-alkyl-heterocyclyl, NH-alkyl-aryl, NH-alkyl-heteroaryl, NH-alkyl-NH 2 , 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, NHSO 2 -alkyl, NHSO 2 -cycloalkyl, NHSO 2 -heterocyclyl, NHSO 2 -aryl, NHSO 2 -heteroaryl, NHSO 2 -alkyl-aryl, NHSO 2 -alkyl-heteroaryl, NO 2 , SH, S-alkyl, S-cycloalkyl, S-heterocyclyl, S-aryl, S-heteroaryl, OH, OCF 3 , 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—(CH 2 ) n —O (n=1, 2 or 3), OC(O)-alkyl, OC(O)-cycloalkyl, OC(O)-heterocyclyl, OC(O)-aryl, OC(O)-heteroaryl, OC(O)-alkyl-aryl, OC(O)-alkyl-heteroaryl, OSO 3 H, OSO 2 -alkyl, OSO 2 -cycloalkyl, OSO 2 -heterocyclyl, OSO 2 -aryl, OSO 2 -heteroaryl, OSO 2 -alkyl-aryl, OSO 2 -alkyl-heteroaryl, OP(O)(OH) 2 , C(O)-alkyl, C(O)-aryl, C(O)-heteroaryl, CO 2 H, CO 2 -alkyl, CO 2 -cycloalkyl, CO 2 -heterocyclyl, CO 2 -aryl, CO 2 -heteroaryl, CO 2 -alkyl-cycloalkyl, CO 2 -alkyl-heterocyclyl, CO 2 -alkyl-aryl, CO 2 -alkyl-heteroaryl, C(O)—NH 2 , 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, SO 2 -alkyl, SO 2 -aryl, SO 2 NH 2 , SO 2 NH-alkyl, SO 2 NH-aryl, SO 2 NH-heteroaryl, SO 2 NH-alkyl-aryl, SO 3 H, SO 2 O-alkyl, SO 2 O-aryl, SO 2 O-alkylaryl, alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, 
 (xi) unsubstituted or substituted heteroaryl, wherein the heteroaryl radical optionally includes one or more, identical or different, substituents selected from the group consisting of F, Cl, Br, I, CF 3 , CN, NH 2 , NH-alkyl, NH-cycloalkyl, NH-heterocyclyl, NH-aryl, NH-heteroaryl, NH-alkyl-cycloalkyl, NH-alkyl-heterocyclyl, NH-alkyl-aryl, NH-alkyl-heteroaryl, NH-alkyl-NH 2 , 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, NHSO 2 -alkyl, NHSO 2 -cycloalkyl, NHSO 2 -heterocyclyl, NHSO 2 -aryl, NHSO 2 -heteroaryl, NHSO 2 -alkyl-aryl, NHSO 2 -alkyl-heteroaryl, NO 2 , SH, S-alkyl, S-aryl, S-heteroaryl, OH, OCF 3 , 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, OSO 3 H, OSO 2 -alkyl, OSO 2 -cycloalkyl, OSO 2 -heterocyclyl, OSO 2 -aryl, OSO 2 -heteroaryl, OSO 2 -alkyl-aryl, OSO 2 -alkyl-heteroaryl, OP(O)(OH) 2 , C(O)-alkyl, C(O)-aryl, C(O)-heteroaryl, CO 2 H, CO 2 -alkyl, CO 2 -cycloalkyl, CO 2 -heterocyclyl, CO 2 -aryl, CO 2 -heteroaryl, CO 2 -alkyl-cycloalkyl, CO 2 -alkyl-heterocyclyl, CO 2 -alkyl-aryl, CO 2 -alkyl-heteroaryl, C(O)—NH 2 , 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 2 NH 2 , SO 2 NH-alkyl, SO 2 NH-aryl, SO 2 NH-heteroaryl, SO 2 NH-alkyl-aryl, SO 3 H, SO 2 O-alkyl, SO 2 O-aryl, SO 2 O-alkyl-aryl, alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, 
 (xii) —C(O)—R17, wherein R17 is alkyl, aryl or heteroaryl, and wherein alkyl and aryl optionally include one or more, same or different, substituents selected from the group consisting of F, Cl, Br, I, CN, CF 3 , NH 2 , NH-alkyl, NH-aryl, N(alkyl) 2 , NO 2 , SH, S-alkyl, OH, OCF 3 , O-alkyl, O-aryl, OSO 3 H, OP(O)(OH) 2 , CHO, CO 2 H, SO 3 H, and alkyl, 
 (xiii) or R11 and R12 together form a cycloalkyl or heterocyclyl. 
 
       
     
     
         66 . The pyrido[2,3-b]pyrazine compound according to  claim 65 , wherein R1 is selected from the group consisting of
 (i) pyrrolyl, furyl, thienyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, imidazolyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, phthalazinyl, indolyl, indazolyl, indolizinyl, quinolinyl, isoquinolinyl, quinoxalinyl, quinazolinyl, carbazolyl, phenazinyl, phenothiazinyl, and acridinyl,   wherein the heteroaryl radicals in (i) are substituted with one radical selected from the group consisting of
 (ii) 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, SO 2 NH-alkyl, SO 2 NH-aryl, SO 2 NH-heteroaryl, SO 2 NH-alkyl-aryl, SO 2 O-alkyl, SO 2 O-aryl, SO 2 O-alkyl-aryl, alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, 
 wherein the alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl radicals in (ii) optionally include one or more, same or different, substituents selected from the group consisting of
 (iii) NH-alkyl, N(alkyl) 2 , S-alkyl, O-alkyl, alkyl, alkyl-OH, alkyl-NH 2 , alkyl-SH, alkyl-O-alkyl, alkyl-O—[(CH 2 ) n —O] m  (n=1, 2 or 3, m=1, 2 or 3), alkyl-NH-alkyl, alkyl-N-(alkyl) 2 , alkyl-5-alkyl, C(O)-alkyl, CO 2 -alkyl, C(O)—NH 2 , C(O)NH-alkyl, C(O)N(alkyl) 2 , SO 2 -alkyl, SO 2 NH-alkyl, SO 2 N(alkyl) 2 , alkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl,
 and wherein the alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl in (iii) optionally include one or more, same or different, substituents selected from the group consisting of 
 (iv) H, F, Cl, Br, I, CF 3 , CHF 2 , CN, NH 2 , NH-alkyl, N(alkyl) 2 , NO 2 , SH, S-alkyl, OH, OCF 3 , OCHF 2 , O-alkyl, alkyl, alkyl-OH, alkyl-O-alkyl, alkyl-O-[(CH 2 ) n —O] m  (n=1, 2 or 3, m=1, 2 or 3), alkyl-NH 2 , alkyl-NH-alkyl, alkyl-N(alkyl) 2 , CH(O), C(O)-alkyl, CO 2 H, CO 2 -alkyl, C(O)—NH 2 , C(O)NH-alkyl, C(O)N(alkyl) 2 , SO 3 H, SO 2 -alkyl, SO 2 NH 2 , SO 2 NH-alkyl, and SO 2 N(alkyl) 2 , 
 
 
   R3 is NHC(O)NH-alkyl or NHC(S)NH-alkyl, wherein the alkyl radical is selected from the group consisting of   (v) methyl, ethyl, n-propyl, 2-propyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, iso-pentyl, neo-pentyl, n-hexyl, 2-hexyl, n-heptyl, n-octyl, ethylenyl (vinyl), ethynyl, propenyl (—CH 2 CH═CH 2 , —CH═CH—CH 3 , —C(═CH 2 )—CH 3 ), propynyl (—CH 2 —C≡CH, —C≡C—CH 3 ), butenyl, butynyl, pentenyl, pentynyl, hexenyl, hexynyl, heptenyl, heptynyl, octenyl, octynyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl, and where the alkyl radials in (v) optionally include one or more, same or different, substituents selected from the group consisting of
 (vii) F, Cl, Br, I, CF 3 , CHF 2 , CN, NH 2 , NH-alkyl, N(alkyl) 2 , NO 2 , SH, S-alkyl, OH, OCF 3 , OCHF 2 , O-alkyl, alkyl, alkyl-OH, alkyl-O—[(CH 2 ) n —O] m  (n=1, 2 or 3, m=1, 2 or 3), alkyl-NH 2 , alkyl-NH-alkyl, alkyl-N(alkyl) 2 , CH(O), C(O)-alkyl, CO 2 H, CO 2 -alkyl, C(O)—NH 2 , C(O)NH-alkyl, C(O)N(alkyl) 2 , SO 3 H, SO 2 -alkyl, SO 2 NH 2 , SO 2 NH-alkyl, and SO 2 N(alkyl) 2 . 
   
     
     
         67 . The pyrido[2,3-b]pyrazine compound according to  claim 65 , wherein R1 is pyrazolyl substituted with one or more alkyl-aryl substituents, wherein the alkyl-aryl radical optionally include one or more, same or different, substituents selected from the group consisting of
 (i) H, F, Cl, Br, I, CF 3 , CHF 2 , CN, NH 2 , NH-alkyl, N(alkyl) 2 , NO 2 , SH, S-alkyl, OH, OCF 3 , OCHF 2 , O-alkyl, alkyl, alkyl-OH, alkyl-O—[(CH 2 ) n —O] m  (n=1, 2 or 3, m=1, 2 or 3), alkyl-NH 2 , alkyl-NH-alkyl, alkyl-N(alkyl) 2 , CH(O), C(O)-alkyl, CO 2 H, CO 2 -alkyl, C(O)—NH 2 , C(O)NH-alkyl, C(O)N(alkyl) 2 , SO 3 H, SO 2 -alkyl, SO 2 NH 2 , SO 2 NH-alkyl, and SO 2 N(alkyl) 2 ,   R3 is NHC(O)NH-alkyl or NHC(S)NH-alkyl, wherein the alkyl radical is selected from the group consisting of   (ii) methyl, ethyl, n-propyl, 2-propyl, n-butyl, sec-butyl, ethylenyl (vinyl), ethynyl, propenyl (—CH 2 CH═CH 2 , —CH═CH—CH 3 , —C(═CH 2 )—CH 3 ), propynyl (—CH 2 —C≡CH, —C≡C—CH 3 ), butenyl, butynyl, cyclopropyl, and cyclobutyl,
 and wherein the alkyl radials in (ii) optionally include one or more, same or different, substituents selected from the group consisting of 
   (iii) F, Cl, Br, I, CF 3 , CHF 2 , CN, NH 2 , NH-alkyl, N(alkyl) 2 , NO 2 , SH, S-alkyl, OH, OCF 3 , OCHF 2 , O-alkyl, alkyl, alkyl-OH, alkyl-O-alkyl, alkyl-O—[(CH 2 ) n —O] m  (n=1, 2 or 3, m=1, 2 or 3), alkyl-NH 2 , alkyl-NH-alkyl, alkyl-N(alkyl) 2 , CH(O), C(O)-alkyl, CO 2 H, CO 2 -alkyl, C(O)—NH 2 , C(O)NH-alkyl, C(O)N(alkyl) 2 , SO 3 H, SO 2 -alkyl, SO 2 NH 2 , SO 2 NH-alkyl, and SO 2 N(alkyl) 2 .   
     
     
         68 . The pyrido[2,3-b]pyrazine compound according to  claim 65 , wherein R1 is (1-benzyl)pyrazol-4-yl, optionally substituted with or more, same or different, substituents selected from the group consisting of
 (i) F, Cl, Br, I, CF 3 , CHF 2 , CN, NH 2 , NH-alkyl, N(alkyl) 2 , NO 2 , SH, S-alkyl, OH, OCF 3 , OCHF 2 , O-alkyl, alkyl, alkyl-OH, alkyl-O-alkyl, alkyl-O—[(CH 2 ) n —O] m  (n=1, 2 or 3, m=1, 2 or 3), alkyl-NH 2 , alkyl-NH-alkyl, alkyl-N(alkyl) 2 , CH(O), C(O)-alkyl, CO 2 H, CO 2 -alkyl, C(O)—NH 2 , C(O)NH-alkyl, C(O)N(alkyl) 2 , SO 3 H, SO 2 NH 2 , SO 2 NH-alkyl, and SO 2 N(alkyl) 2 ,   R3 is NHC(O)NH-alkyl or NHC(S)NH-alkyl, wherein the alkyl radical is selected from the group consisting of   (i) methyl, ethyl, n-propyl, 2-propyl, n-butyl, sec-butyl, ethylenyl (vinyl), ethynyl, propenyl (—CH 2 CH═CH 2 , —CH═CH—CH 3 , —C(═CH 2 )—CH 3 ), propynyl (—CH 2 —C≡CH, —C≡C—CH 3 ), cyclopropyl, and cyclobutyl,
 and wherein the alkyl radicals in (i) optionally include one or more, same or different, substituents selected from the group consisting of 
 (ii) F, Cl, Br, I, CF 3 , CHF 2 , CN, NH 2 , NH-alkyl, N(alkyl) 2 , NO 2 , SH, S-alkyl, OH, OCF 3 , OCHF 2 , O-alkyl, alkyl, alkyl-OH, alkyl-O-alkyl, alkyl-O—[(CH 2 ) n —O] m  (n=1, 2 or 3, m=1, 2 or 3), alkyl-NH 2 , alkyl-NH-alkyl, alkyl-N(alkyl) 2 , CH(O), C(O)-alkyl, CO 2 H, CO 2 -alkyl, C(O)—NH 2 , C(O)NH-alkyl, C(O)N(alkyl) 2 , SO 3 H, SO 2 NH 2 , SO 2 NH-alkyl, and SO 2 N(alkyl) 2 . 
   
     
     
         69 . A pharmaceutical composition comprising a pharmacologically active amount of at least one compound according to  claim 65 . 
     
     
         70 . The pharmaceutical composition according to  claim 69 , where the at least one compound is present in a unit dose of from 0.001 mg to 100 mg per kg of a patient's bodyweight. 
     
     
         71 . The pharmaceutical composition according to  claim 69 , further comprising at least one pharmaceutically acceptable carrier and/or excipient.