5-alkynyl-pyrimidines

A compound of general formula (1),

• wherein
• R3 is selected from a group consisting of C3-8cycloalkyl, 3-8 membered heterocycloalkyl, C6-10aryl and 5-12 membered heteroaryl, optionally substituted by one or more identical or different R4;
• and
• R1 is selected from a group consisting of C3-8cycloalkyl, 3-13 membered heterocycloalkyl, and 2-6 membered heteroalkyl, optionally substituted by one or more identical or different R5;
• and
• R2 is selected from a group consisting of C1-4alkyl, 3-8 membered heteroalkyl, C1-4haloalkyl, C3-8cycloalkyl, 3-8 membered heterocycloalkyl, —ORv, —NRvRv′, —SRv, —CF3, —CHF2, —CH2F, —CN, —NC and —NO2, and
• each R4 is selected from Ra and Rb;
• and
• each Ra independently denotes hydrogen or is selected from a group consisting of C1-6alkyl, 2-6 membered heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, C4-16cycloalkylalkyl, C6-10aryl, C7-16arylalkyl, 5-12 membered heteroaryl, 6-18 membered heteroarylalkyl, 3-14 membered heterocycloalkyl and 4-14 membered heterocycloalkylalkyl, wherein Ra is optionally substituted by one or identical or different Rb and/or Rc4;
• each Rb is selected independently from a group consisting of —ORc41, C1-3haloalkyloxy, —OCF3, —OCHF2, —SRc41, —NRc41Rc42,
• —ONRc41Rc42, —N(ORc41)Rc42, —N(Rg)NRc41Rc42, halogen, —CF3, —CHF2, —CH2F, —CN, —NC, —OCN, —SCN, —NO, —NO2, ═N2, and —N3, and
• each R4, Rc41 and Rc42 is independently hydrogen or selected from a group consisting of C1-6alkyl, 2-6 membered heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, C4-16cycloalkylalkyl, C6-10aryl, C7-16arylalkyl, 5-12 membered hetero-aryl, 6-18 membered heteroarylalkyl, 3-14 membered heterocycloalkyl and4-14 membered heterocycloalkylalkyl, wherein Rc41 and Rc42 independently optionally being substituted by one or more identical or different Rd and/or Re4, and where Rc41 and Rc42 taken together may form a 3-8 membered heterocyclalkyl residue via a shared C—, N—O— or S-atom, and
• each Rd is selected independently from a group consisting of —ORe41, C1-3 haloalkyloxy, —OCF3, —OCHF2, —SRe41, —NRe41Re42,
• —ONRe41Re42, —N(Rg)NRe41Re42, halogen, —CF3, —CN, —NC, —OCN, —SCN, —NO, —NO2, ═N2, and —N3;
• and
• each Re4, Re41 and Re42 independently denotes hydrogen or is selected from a group consisting of C1-6alkyl, 2-6 membered heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, C4-16cycloalkylalkyl, C6-10aryl, C7-16arylalkyl, 5-12 membered hetero-aryl, 6-18 membered heteroarylalkyl, 3-14 membered heterocycloalkyl and4-14 membered heterocycloalkylalkyl, wherein Re41 and Re42 are optionally independently substituted by one or more identical or different Rf and/or Rg4, and where Re41 and/or Re42 taken together may form a 3-8 membered heterocyclalkyl residue via a shared C—, N—O— or S-atom and
• each Rf denotes a suitable group selected independently from a group consisting of ═O, —ORg41, C1-3haloalkyloxy, —OCF3, —OCHF2, ═S, —SRg41, ═NRg41, ═NORg41, ═NNRg41Rg42, ═NN(Rh)C(O)NRg41Rg42, —NRg41Rg42,
• —ONRg41Rg42, —N(Rh)NRg41Rg42, halogen, —CF3, —CN, —NC, —OCN, —SCN, —NO, —NO2, ═N2, —N3, —S(O)Rg41, —S(O)ORg41, —S(O)2Rg41, —S(O)2ORg41, —S(O)NRg41Rg42, —S(O)2NRg41Rg42, —OS(O)Rg41, —OS(O)2Rg41, —OS(O)2ORg41, —OS(O)NRg41Rg42, —OS(O)2NRg41Rg42, —C(O)Rg41, —C(O)ORg41, —C(O)SRg41, —C(O)NRg41Rg42, —C(O)N(Rh)NRg41Rg42, —C(O)N(Rh)ORg41, —C(NRh)NRg41Rg42, —C(NOH)Rg41, —C(NOH)NRg41Rg42, —OC(O)Rg41, —OC(O)ORg41, —OC(O)SRg41, —OC(O)NRg41Rg42, —OC(NRh)NRg41Rg42, —SC(O)Rg41, —SC(O)ORg41, —SC(O)NRg41Rg42, —SC(NRh)NRg41Rg42, —N(Rh)C(O)Rg41, —N[C(O)Rg41]2, —N(ORh)C(O)Rg41, —N(Rh)C(NRh′)Rg41, —N(Rh)N(Rh′)C(O)Rg41, —N[C(O)Rg43]NRg41Rg42, —N(Rh)C(S)Rg41, —N(Rh)S(O)Rg41, —N(Rh)S(O)ORg41, —N(Rh)S(O)2Rg41, —N[S(O)2Rg41][S(O)2Rg42], —N(Rh)S(O)2ORg41, —N(Rh)S(O)2NRg41Rg42, —N(Rh)[S(O)2]2Rg41, —N(Rh)C(O)ORg41, —N(Rh)C(O)SRg41, —N(Rh)C(O)NRg41Rg42, —N(Rh)C(O)NRh′NRg41Rg42, —N(Rh)N(Rh′)C(O)NRg41Rg42, —N(Rh)C(S)NRg41Rg42, —[N(Rh)C(O)][N(Rh′)C(O)]Rg41, —N(Rh)[C(O)]2Rg41, —N{[C(O)]2Rg41}{[C(O)]2Rg42}, —N(Rh)[C(O)]2ORg41, —N(Rh)[C(O)]2NRg41Rg42, —N{[C(O)]2ORg41}{[C(O)]2ORg41}, —N{[C(O)]2NRg41Rg42}{[C(O)]2NRg41Rg42}, —[N(Rh)C(O)][N(Rh′)C(O)]ORg41, —N(Rh)C(NRh′)ORg41, —N(Rh)C(NOH)Rg41, —N(Rh)C(NRh′)SRg41, —N(Rh)C(NRh′)NRg41Rg42;
• and —N═C(Rh)NRg41Rg42;
• and
• each Rg4, Rg41, Rg42 and Rg43 independently denotes hydrogen or is selected from a group consisting of C1-6alkyl, 2-6 membered heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, C4-16cycloalkylalkyl, C6-10aryl, C7-16arylalkyl, 5-12 membered hetero-aryl, 6-18 membered heteroarylalkyl, 3-14 membered heterocycloalkyl and 4-14 membered heterocycloalkylalkyl, where Rg41 and/or Rg42 and/or Rg43 taken together may form a 3-8 membered heterocyclalkyl residue via a shared C—, —N—O— or S-atom, wherein each Rg41, Rg42 and Rg43 is optionally independently substituted by one or more identical or different Rh″;
• and
• each Rh, Rh′ and Rh″ is selected independently from a group consisting of hydrogen, C1-6 alkyl, 2-6 membered heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, C4-16mcycloalkylalkyl, C6-10 aryl, C7-16arylalkyl, 5-12 membered heteroaryl, 6-18 membered heteroarylalkyl, 3-14 membered heterocycloalkyl and 4-14 membered heterocycloalkylalkyl, where Rh and Rh′ taken together may form a 3-8 membered heterocyclalkyl residue via a shared C—, N—, O— or S-atom, and
• each R5 denotes a group selected from Ra5 and/or Rb5,
• each Ra5 independently denotes hydrogen or is selected from a group consisting of C1-6alkyl, 2-6 membered heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, C4-16cycloalkylalkyl, C6-10aryl, C7-16arylalkyl, 5-12 membered heteroaryl, 6-18 membered heteroarylalkyl, 3-14 membered heterocycloalkyl, and 4-14 membered heterocycloalkylalkyl, wherein Ra5 optionally being substituted by one or more identical or different Rb5 and/or Rc51;
• and
• each Rb5 is selected independently from a group consisting of ═O, ORc5, C1-3haloalkyloxy, —OCF3, —OCHF2, ═S, —=SRc5, ═NRc5, ═NORc5, ═NNRc5Rc55, ═NN(Rg5)C(O)NRc5Rc55, —ONRc5Rc55, —N(ORc5)Rc55, —N(Rg5)NRc5Rc55, halogen, —CF3, —CHF2, —CH2F, —CN, —NC, —OCN, —SCN, —NO, —NO2, ═N2, —N3, —S(O)Rc5, —S(O)ORc5, —S(O)2Rc5, —S(O)2ORc5, —S(O)NRc5Rc55, —S(O)2NRc5 Rc55, —OS(O)Rc5, —OS(O)2Rc5, —OS(O)2ORc5, —OS(O)NRc5Rc55, —OS(O)2NRc5Rc55, —C(O)Rc5, —C(O)ORc5, —C(O)SRc5, —C(O)NRc5Rc55, —C(O)N(Rg5)NRc5Rc55, —C(O)N(Rg5)ORc5, —C(NRg5)NRc5Rc55, —C(NOH)Rc5, —C(NOH)NRc5Rc55, —OC(O)Rc5, —OC(O)ORc5, —OC(O)SRc5, —OC(O)NRc5Rc55, —OC(NRg5)NRc5Rc55, —SC(O)Rc5, —SC(O)ORc5, —SC(O)NRc5Rc55, —SC(NRg5)NRc5Rc55, —N(Rg5)C(O)Rc5, —N[C(O)Rc5]2, —N(ORg5)C(O)Rc5, —N(Rg5)C(NRg5)Rc5, —N(Rg5)N(Rg55)C(O)Rc5, —N[C(O)Rc5]NRc55Rc555, —N(Rg5)C(S)Rc5, —N(Rg5)S(O)Rc5, —N(Rg5)S(O)ORc5, —N(Rg5)S(O)2Rc5, —N[S(O)2Rc5]2, —N(Rg5)S(O)2ORc5, —N(Rg5)S(O)2NRc5Rc55, —N(Rg5)[S(O)2]2Rc5, —N(Rg5)C(O)ORc5, —N(Rg5)C(O)SRc5, —N(Rg5)C(O)NRc5Rc55, —N(Rg5)C(O)NRg55NRc5Rc55, —N(Rg5)N(Rg55)C(O)NRc5Rc55, —N(Rg5)C(S)NRc5Rc55, —[N(Rg5)C(O)]2Rc5, —N(Rg5)[C(O)]2Rc5, —N{[C(O)]2Rc5}2—N(Rg5)[C(O)]2ORc5, —N(Rg5)[C(O)]2NRc5Rc55, —N{[C(O)]2ORc5}2, —N{[C(O)]2NRc5Rc55}2, —[N(Rg5)C(O)]2ORc5, —N(Rg5)C(NRg55)ORc5, —N(Rg5)C(NOH)Rc5, —N(Rg5)C(NRg55)SRc5, —N(Rg5)C(NRg55)NRc5Rc55 and —N═C(Rg5)NRc5Rc55, where Rc5and/or Rc55 and/or Rc555 taken together may form a 3-8 membered heterocyclalkyl residue via a shared C—, N—, O— or S-atom;
• and
• each Rc51, Rc5, Rc55 and Rc555 independently denotes hydrogen or is selected from a group consisting of C1-6alkyl, 2-6 membered heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, C4-16cycloalkylalkyl, C6-10aryl, C7-16arylalkyl, 5-12 membered hetero-aryl, 6-18 membered heteroarylalkyl, 3-14 membered heterocycloalkyl and 4-14 membered heterocycloalkylalkyl, wherein each Rc51, Rc5, Rc55 and/or Rc555 optionally being independently substituted by one or more identical or different Rd5 and/or Re51;
• and
• each Rd5 is selected independently from a group consisting of ═O, —ORe5, C1-3haloalkyloxy, —OCF3, —OCHF2, ═S, —SRe5, ═NRe5, ═NORe5, ═NNRe5Re55, ═NN(Rg5)C(O)NRe5Re55, —NRe5Re55, —ONRe5Re55, —N(Rg5)NRe5Re55, halogen, —CF3, —CHF2, —CH2F, —CN, —NC, —OCN, —SCN, —NO, —NO2, ═N2, —N3, —S(O)Re5, —S(O)ORe5, —S(O)2Re5, —S(O)2ORe5, —S(O)NRe5Re55, —S(O)2NRe5Re55, —OS(O)Re5, —OS(O)2Re5, —OS(O)2ORe5, —OS(O)NRe5Re55, —OS(O)2NRe5Re55, —C(O)Re5, —C(O)ORe5, —C(O)SRe5, —C(O)NRe5Re55, —C(O)N(Rg5)NRe5Re55, —C(O)N(Rg5)ORe5, —C(NRg5)NRe5Re55, —C(NOH)Re5, —C(NOH)NRe5Re55, —OC(O)Re5, —OC(O)ORe5, —OC(O)SRe5, —OC(O)NRe5Re55, —OC(NRg5)NRe5Re55, —SC(O)Re5, —SC(O)ORe5, —SC(O)NRe5Re55, —SC(NRg5)NRe5Re55, —N(Rg5)C(O)Re5, —N[C(O)Re5]2, —N(ORg5)C(O)Re5, —N(Rg5)C(NRg55)Re5, —N(Rg5)N(Rg55)C(O)Re5, —N[C(O)Re5]NRe55Re555, —N(Rg5)C(S)Re5, —N(Rg5)S(O)Re5, —N(Rg5)S(O)ORe5 —N(Rg5)S(O)2Re5, —N[S(O)2Re5]2, —N(Rg5)S(O)2ORe5, —N(Rg5)S(O)2NRe5Re55, —N(Rg5)[S(O)2]2Re5, —N(Rg5)C(O)ORe5, —N(Rg5)C(O)SRe5, —N(Rg5)C(O)NRe5Re55, —N(Rg5)C(O)NRg55NRe5Re55, —N(Rg5)N(Rg55)C(O)NRe5Re55, —N(Rg5)C(S)NRe5Re55, —[N(Rg5)C(O)]2Re5, —N(Rg5)[C(O)]2Re5, —N{[C(O)]2Re5}2, —N(Rg5) [C(O)]2ORe5, —N(Rg5)[C(O)]2NRe5Re55, —N{[C(O)]2ORe5}2, —N{[C(O)]2NRe5Re55}2, —[N(Rg5)C(O)]2ORe5, —N(Rg5)C(NRg55)ORe5, —N(Rg5)C(NOH)Re5, —N(Rg5)C(NRg55)SRe5, —N(Rg5)C(NRg55)NRe5Re55 and —N═C(Rg5)NRe5Re55, where Re5and/or Re55 and/or Re555 taken together may form a 3-8 membered heterocyclalkyl residue via a shared C—, N—, O— or S-atom;
• and
• each Re51, Re5, Re55 and Re555 independently denotes hydrogen or is selected from a group consisting of C1-6alkyl, 2-6 membered heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, C4-16cycloalkylalkyl, C6-10aryl, C7-16arylalkyl, 5-12 membered heteroaryl, 6-18 membered heteroarylalkyl, 3-14 membered heterocycloalkyl and 4-14 membered heterocycloalkylalkyl wherein each Re51, Re5, Re55 and/or Re555 optionally being independently substituted by one or more identical or different Rf5 and/or Rg51;
• and
• each Rf5 is selected independently from a group consisting ═O, —ORg52, C1-3haloalkyloxy, —OCF3, —OCHF2, ═S, —SRg52, ═NRg52, ═NORg52, ═NNRg52Rg53 ═NN(Rh5)C(O)NRg52Rg53, —NRg52Rg53, —ONRg52Rg53, —N(Rh5)NRg52Rg53, halogen, —CF3, —CHF2, —CH2F, —CN, —NC, —OCN, —SCN, —NO, —NO2, ═N2, —N3, —S(O)Rg52, —S(O)ORg52, —S(O)2Rg52, —S(O)2ORg52, —S(O)NRg52Rg53, —S(O)2NRg52Rg53, —OS(O)Rg52, —OS(O)2Rg52, —OS(O)2ORg52, —OS(O)NRg52Rg53, —OS(O)2NRg52Rg53, —C(O)Rg52, —C(O)ORg52, —C(O)SRg52, —C(O)NRg52Rg53, —C(O)N(Rh5)NRg52Rg53, —C(O)N(Rh5)ORg52 —C(NRh5)NRg52Rg53, —C(NOH)Rg52, —C(NOH)NRg52Rg53, —OC(O)Rg52, —OC(O)ORg52, —OC(O)SRg52, —OC(O)NRg52Rg53, —OC(NRh5)NRg52Rg53, —SC(O)Rg52, —SC(O)ORg52, —SC(O)NRg52Rg53, —SC(NRh5)NRg52Rg53, —N(Rh5)C(O)Rg52, —N[C(O)Rg52]2, —N(ORh5)C(O)Rg52, —N(Rh5)C(NRh55)Rg52, —N(Rh5)N(Rh55)C(O)Rg52, —N[C(O)Rg52]NRg53Rg54, —N(Rh5)C(S)Rg52, —N(Rh5)S(O)Rg52, —N(Rh5)S(O)ORg52, —N(Rh5)S(O)2Rg52, —N[S(O)2Rg52]2, —N(Rh5)S(O)2ORg52, —N(Rh5)S(O)2NRg52Rg53, —N(Rh5)[S(O)2]2Rg52, —N(Rh5)C(O)ORg52, —N(Rh5)C(O)SRg52 —N(Rh5)C(O)NRg52Rg53, —N(Rh5)C(O)NRh55NRg52Rg53, —N(Rh5)N(Rh55)C(O)NRg52Rg53, —N(Rh5)C(S)NRg52Rg53, —[N(Rh5)C(O)]2Rg52, —N(Rh5)[C(O)]2Rg52, —N{[C(O)]2Rg52}2, —N(Rh5)[C(O)]2ORg52, —N(Rh5)[C(O)]2NRg52Rg53, —N{[C(O)]2ORg52}2, —N{[C(O)]2NRg52Rg53}2, —[N(Rh5)C(O)]2ORg52 —N(Rh5)C(NRh55)ORg52, —N(Rh5)C(NOH)Rg52 —N(Rh5)C(NRh55)SRg52 —N(Rh5)C(NRh55)NRg52Rg53;
• and
• —N═C(Rh5)NRg52Rg53;
• and
• each Rg5, Rg51, Rg52, Rg53, Rg54 and Rg55 independently denotes hydrogen or is selected from a group consisting of C1-6alkyl, 2-6 membered heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, C4-16cycloalkylalkyl, C6-10aryl, C7-16arylalkyl, 5-12 membered heteroaryl, 6-18 membered heteroarylalkyl, 3-14 membered heterocycloalkyl and 4-14 membered heterocycloalkylalkyl wherein each Rg5, Rg51, Rg52, Rg53, Rg54 and Rg55 optionally being independently substituted by one or more identical or different Rh51;
• and
• each Rh51, Rh5, Rh55 and Rh555 is selected independently from a group consisting of hydrogen, C1-6alkyl, 2-6 membered heteroalkyl, C1-6haloalkyl, C3-10cycloalkyl, C4-16cycloalkylalkyl, C6-10aryl, C7-16arylalkyl, 5-12 membered heteroaryl, 6-18 membered heteroarylalkyl, 3-14 membered heterocycloalkyl and 4-14 membered heterocycloalkylalkyl;
• and
• each Rv and Rv′ is selected independently from a group consisting of hydrogen, C1-6alkyl, 2-6 membered heteroalkyl, and C1-6haloalkyl, optionally in the form of, the tautomers, the racemates, the enantiomers, the diastereomers, and optionally the pharmacologically acceptable salts thereof.