Pyrimido [5,4-D] pyrimidine derivatives for the inhibition of tyrosine kinases

A compound of general formula (1)

• wherein
• R1 is a group optionally substituted by one or more, identical or different Rb and/or Rc, selected from among C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, C6-10aryl, 5-12 membered heteroaryl and 3-14 membered heterocycloalkyl, or
• a suitable substituent, selected from among —ORc, —SRc, —NRcRc, —NRgNRcRc and —S(O)Rc;
• R2 is a group optionally substituted by one or more, identical or different Rb and/or Rc, selected from among C1-6alkyl, C1-6haloalkyl, C3-10cycloalkyl, C6-10aryl, 5-12 membered heteroaryl and 3-14 membered heterocycloalkyl;
• R4 is C1-4alkyl;
• X1, X2 and X3 are each —CR4*═, and R4* is hydrogen;
• X4 is —N═;
• X5 is —CH═,
• L1 is selected from among —CH2—, —NH—, —NMe-, —O— and —S—;
• L2 is selected from among —C(O)NH—, —C(O)N(C1-4alkyl)-, —NHC(O)—, —N(C1-4alkyl)C(O)— and —C(O)—,
• while in the notation used above L2 on the left binds to R2;
• Q denotes a bond or a methylene group;
• each Rb is a suitable substituent and is selected independently of one another from among —ORc, —SRc, —NRcRc, —ONRcRc, —N(ORc)Rc, —NRgNRcRc, halogen, —CN, —NO2, —N3, —C(O)Rc, —C(O)ORc, —C(O)NRcRc, —C(O)NRgNRcRc, —C(O)NRgORc, —C(NRg)Rc, —N═CRcRc, —C(NRg)ORc, —C(NRg)NRcRc, —C(NRg)NRgNRcRc, —C(NORg)Rc, —C(NORg)NRcRc, —C(NNRgRg)Rc, —OS(O)Rc, —OS(O)ORc, —OS(O)NRcRc, —OS(O)2Rc, —OS(O)2ORc, —OS(O)2NRcRc, —OC(O)Rc, —OC(O)ORc, —OC(O)NRcRc, —OC(NRg)Rc, —OC(NRg)NRcRc, —ONRgC(O)Rc, —S(O)RB, —S(O)ORc, —S(O)NRcRc, —S(O)2Rc, —S(O)2ORc, —S(O)2NRcRc, —NRgC(O)Rc, —NRgC(O)ORc, —NRgC(O)NRcRc, —NRgC(O)NRgNRcRc, —NRgC(NRg)Rc, —N═CRcNRcRc, —NRgC(NRg)ORc, —NRgC(NRg)NRcRc, —NRgC(NORg)Rc, —NRgS(O)Rc, —NRgS(O)ORc, —NRgS(O)2Rc, —NRgS(O)2ORc, —NRgS(O)2NRcRc, —NRgNRgC(O)Rc, —NRgNRgC(O)NRcRc, —NRgNRgC(NRg)Rc and —N(ORg)C(O)Rc and the bivalent substituents ═O, ═S, ═NRg, ═NORg, ═NNRgRg and ═NNRgC(O)NRgRg, while these bivalent substituents may only be substituents in non-aromatic ring systems;
• each Rc independently denotes hydrogen or a group optionally substituted by one or more, identical or different Rd and/or Re, selected from among C1-6alkyl, 2-6 membered heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, C6-10aryl, 5-12 membered heteroaryl and 3-14 membered heterocycloalkyl;
• each Rd is a suitable substituent and is independently selected from among —ORe, —SRe, —NReRe, —ONReRe, —N(ORe)Re, —N(Rg)NReRe, halogen, —CN, —NO, —NO2, —N3, —C(O)Re, —C(O)ORe, —C(O)NReRe, —C(O)NRgNReRe, —C(O)NRgORe, —C(NRg)Re, —N═CReRe, —C(NRg)ORe, —C(NRg)NReRe, —C(NRg)NRgNReRe, —C(NORg)Re, —C(NORg)NReRe, —C(NNRgRg)Re, —OS(O)Re, —OS(O)ORe, —OS(O)NReRe, —OS(O)2Re, —OS(O)2ORe, —OS(O)2NReRe, —OC(O)Re, —OC(O)ORe, —OC(O)NReRe, —OC(NRg)Re, —OC(NRg)NReRe, —ONRgC(O)Re, —S(O)Re, —S(O)ORe, —S(O)NReRe, —S(O)2Re, —S(O)2ORe, —S(O)2NReRe, —NRgC(O)Re, —NRgC(O)ORe, —NRgC(O)NReRe, —NRgC(O)NRgNReRe, —NRgC(NRg)Re, —N═CReNReRe, —NRgC(NRg)ORe, —NRgC(NRg)NReRe, —NRgC(NRg)SRe, —NRgC(NORg)Re, —NRgS(O)Re, —NRgS(O)ORe, —NRgS(O)2Re, —NRgS(O)2ORe, —NRgS(O)2NReRe, —NRgNRgC(O)Re, —NRgNRgC(O)NReRe, —NRgNRgC(NRg)Re and —N(ORg)C(O)Re and the bivalent substituents ═O, ═S, ═NRg, ═NORg, ═NNRgRg and ═NNRgC(O)NRgRg, while these bivalent substituents may only be substituents in non-aromatic ring systems;
• each Re independently denotes hydrogen or a group optionally substituted by one or more, identical or different Rf and/or Rg, selected from among C1-6alkyl, 2-6 membered heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, C6-10aryl, 5-12 membered heteroaryl and 3-14 membered heterocycloalkyl;
• each Rf is a suitable substituent and is independently selected from among —ORg, —SRg, —NRgRg, —ONRgRg, —N(ORg)Rg, —N(Rh)NRgRg, halogen, —CN, —NO2, —N3, —C(O)Rg, —C(O)ORg, —C(O)NRgRg, —C(O)NRhNRgRg, —C(O)NRhORg, —C(NRh)Rg, —N═CRgRg, —C(NRh)ORg, —C(NRh)NRgRg, —C(NRh)NRhNRgRg, —C(NORh)Rg, —C(NORh)NRgRg, —C(NNRhRh)Rg, —OS(O)Rg, —OS(O)ORg, —OS(O)NRgRg, —OS(O)2Rg, —OS(O)2ORg, —OS(O)2NRgRg, —OC(O)Rg, —OC(O)ORg, —OC(O)NRgRg, —OC(NRh)Rg, —OC(NRh)NRgRg, —ONRhC(O)Rg, —S(O)Rg, —S(O)ORg, —S(O)NRgRg, —S(O)2Rg, —S(O)2ORg, —S(O)2NRgRg, —NRhC(O)Rg, —NRhC(O)ORg, —NRhC(O)NRgRg, —NRhC(O)NRhNRgRg, —NRhC(NRh)Rg, —N═CRgNRgRg, —NRhC(NRh)ORg, —NRhC(NRh)NRgRg, —NRhC(NORh)Rg, —NRhS(O)Rg, —NRhS(O)ORg, —NRhS(O)2Rg, —NRhS(O)2ORg, —NRhS(O)2NRgRg, —NRhNRhC(O)Rg, —NRhNRhC(O)NRgRg, —NRhNRhC(NRh)Rg and —N(ORh)C(O)Rg and the bivalent substituents ═O, ═S, ═NRh, ═NORh, ═NNRhRh and ═NNRhC(O)NRhRh, while these bivalent substituents may only be substituents in non-aromatic ring systems;
• each Rg independently denotes hydrogen or a group optionally substituted by one or more, identical or different Rh, selected from among C1-6alkyl, 2-6 membered heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, C6-10aryl, 5-12 membered heteroaryl and 3-14 membered heterocycloalkyl;
• each Rh is independently selected from among hydrogen, C1-6alkyl, 2-6 membered heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, C6-10aryl, 5-12 membered heteroaryl and 3-14 membered heterocycloalkyl;
• or the compounds of formula (1) may optionally also be in the form of a tautomer, racemate, enantiomer, diastereomer or a mixture thereof, or as respective pharmacologically acceptable salts of all the above-mentioned forms.