Map4k1 inhibitors

1) Compound of formula (I)

• wherein
• A is selected from a single bond, —CH2— or —O—;
• E is —(CH2)n— with n=1 or 2;
• G is —(CH2)— and with the condition, that the cyclic substructure comprising E-N-G is a 4 to 5 membered heterocycloalkyl;
• Q is selected from N or C—R2;
• R1 is selected from
• —NO2;
• —CN;
• C1-4-alkyl optionally substituted by —OH or 1 to 3-F;
• cyclopropyl;
• 4 to 6 membered heterocycloalkyl or heterocycloalkenyl, both with 1-2 nitrogen atoms, but always linked via a carbon atom to the phenyl group of compounds of formula (I) and both optionally substituted by C1-4-alkyl;
• phenyl optionally substituted by halogen, —CN, C1-4-alkyl, C1-4-haloalkyl, C3-6-cycloalkyl, O—C1-4-alkyl, O—C3-6-cycloalky, C1-3-alkinyl, —C(O)—Rd, SRd, SORd, SO2Rd, SONRd, SON(H)Rd, —SO2—NH2, —SO2—N(H)—Rd or —SO2—N(Rd)2, wherein Rd is selected from methyl, ethyl, cyclopropyl, isopropyl and tert·butyl;
• 5 to 6 membered heteroaryl with 1, 2 or 3 heteroatoms selected from N, O or S and optionally substituted by 1 or 2 of the following substituents:
• halogen, —CN, C1-4-alkyl, C1-4-haloalkyl, C3-6-cycloalkyl, O—C1-4-alkyl, O—C3-6-cycloalkyl, C1-3-alkinyl, SRd, SORd, SO2Rd, SONRd or SON(H)Rd wherein Rd is selected from methyl, ethyl, cyclopropyl, isopropyl and tert·butyl;
• —O—CH3;
• —O—CH(CH3)2;
• —O—CHF2;
• —O—CF3;
• —O—CHRa-phenyl optionally substituted by one, two or three of the following substituents:
• halogen, —CN, C1-4-alkyl optionally substituted by one or more —F, O—C1-4-alkyl, C1-6-alkinyl-OH or —SO2—CH3 and with Ra selected from —H, —F or —CH3, —CF3, —CH2—CH3, —CH(CH3)2 or -cyclopropyl;
• —O—CHRa-6 membered heteroaryl optionally substituted one, two or three of the following substituents:
• halogen, —CN, C1-4-alkyl optionally substituted by one or more —F or —SO2—CH3 and with Ra selected from —H, —F or —CH3, —CF3, —CH2—CH3, —CH(CH3)2 or -cyclopropyl;
• —COORa with Ra selected from —H or —CH3;
• C(═O)-methyl, optionally substituted by 1 to 3-F;
• —C(═O)—NRbRc wherein Rb is selected from —H, —CH3 or —CH2—CH3 and wherein Rc is selected from —H, —CH3, —CH2—CH3, cyclohexyl, phenyl or 5 to 6 membered heteroaryl, all optionally substituted by one or two halogen, —CN, —SO2—CH3 or C1-4-alkyl, optionally substituted one or more times with halogen;
• —S—CRfRgRh, wherein Rf is selected from —H or —F, wherein Rg is selected from —H, —F or —CH3 and wherein Rh is selected from H, F, —CH3 or C5-6-cycloalkyl or phenyl;
• R2 is selected from —H;
• R4 is selected from
• C1-6-alkyl, C3-6-cycloalkyl or C1-3-alkyl-C3-6-cycloalkyl, all optionally substituted one or independently more times by
• —F, —Cl, —Br, —CN;
• —OH, —ORi wherein Ri is selected from C1-4-alkyl or C3-6-Cycloalkyl, both optionally substituted one or more times by halogen,
• —CF3, —CHF2, —CH2F, or —CH2—CF3;
• —NRjRk wherein Rj and Rk are independently selected from —H and C1-C4-alkyl,
• —CH2—O—CH3 or
• C3-4 cycloalkyl or 4-6 membered heterocycloalkyl, both optionally substituted by (═O), or optionally substituted one or more times by F or CH3;
• C6-8-spiro-alkyl and C5-7-bicyclo-alkyl
• phenyl or 5 to 6 membered heteroaryl, both optionally substituted one or more times by
• halogen, —CN,
• —CF3, —CHF2, —CH2F,
• C1-4-alkyl optionally substituted with one or more halogen;
• C3-6-cycloalkyl;
• O—C1-4-alkyl,
• O—C3-6-cycloalky,
• C1-3-alkinyl,
• NRjRk wherein Rj and Rk are independently selected from —H and C1-C4-alkyl
• SRd, SORd, SO2Rd, SONRd or SON(H)Rd wherein Rd is selected from methyl, ethyl, cyclopropyl, isopropyl and tert·butyl;
• or
• phenyl is optionally substituted one or more times by —C(O)NRjRk wherein Rj and Rk are independently selected from —H and C1-C4-alkyl or
• 5 to 6 membered heteroaryl is optionally substituted one or more times by —OH;
• C(═O)—Rl in which Rl is selected from
• C1-4-alkyl, C3-6-cycloalkyl or C3-6-heterocycloalkyl, both optionally substituted one or more times by
• —F, —Cl, —Br, —CN;
• —OH, —ORi with Ri selected from C1-4-alkyl or C3-6Cycloalkyl), —CF3, —CHF2, —CH2F;
• —NRjRk wherein Rj and Rk are independently selected from —H and C1-C4-alkyl
• phenyl or 5 to 6 membered heteroaryl, both optionally substituted one or more times by
• halogen, —CN,
• —CF3, —CHF2, —CH2F,
• C1-4-alkyl optionally substituted with one or more halogen;
• C3-6-cycloalkyl;
• O—C1-4-alkyl,
• O—C3-6-cycloalky,
• C1-3-alkinyl,
• —NRjRk wherein Rj and Rk are independently selected from —H and C1-C4-alkyl
• SRd, SORd, SO2Rd, SONRd or SON(H)Rd wherein Rd is selected from methyl, ethyl, cyclopropyl, isopropyl and tert·butyl;
• phenyl or 5 to 6 membered heteroaryl, both optionally substituted one or more times by
• halogen, —CN,
• —CF3, —CHF2, —CH2F,
• C1-4-alkyl optionally substituted with one or more halogen;
• C3-6-cycloalkyl;
• O—C1-4-alkyl,
• O—C3-6-cycloalky,
• C1-3-alkinyl,
• —NRjRk wherein Rj and Rk are independently selected from —H and C1-C4-alkyl
• SRd, SORd, SO2Rd, SONRd or SON(H)Rd wherein Rd is selected from methyl, ethyl, cyclopropyl, isopropyl and tert·butyl;
• C(═O)—NRoRp wherein Ro and Rp are independently selected from
• H
• C1-4-alkyl, C3-6-cycloalkyl or C1-3-alkyl-C3-6-cycloalkyl, both optionally substituted one or more times by
• —F, —Cl, —Br, —CN;
• —OH, —ORi with Ri selected from C1-4-alkyl or C3-6-cycloalkyl, —CF3, —CHF2, —CH2F;
• —NRjRk wherein Rj and Rk are independently selected from —H and C1-C4-alkyl
• phenyl or 5 to 6 membered heteroaryl, both optionally substituted one or more times by
• halogen, —CN,
• —CF3, —CHF2, —CH2F,
• C1-4-alkyl optionally substituted with one or more halogen;
• C3-6-cycloalkyl;
• O—C1-4-alkyl,
• O—C3-6-cycloalky,
• C1-3-alkinyl,
• —NRjRk wherein Rj and Rk are independently selected from —H and C1-C4-alkyl
• SRd, SORd, SO2Rd, SONRd or SON(H)Rd wherein Rd is selected from methyl, ethyl, cyclopropyl, isopropyl and tert·butyl;
• phenyl or 5 to 6 membered heteroaryl, both optionally substituted one or more times by
• halogen, —CN,
• —CF3, —CHF2, —CH2F,
• C1-4-alkyl optionally substituted with one or more halogen;
• C3-6-cycloalkyl;
• O—C1-4-alkyl,
• O—C3-6-cycloalky,
• C1-3-alkinyl,
• —NRjRk wherein Rj and Rk are independently selected from —H and C1-C4-alkyl
• SRd, SORd, SO2Rd, SONRd or SON(H)Rd wherein Rd is selected from methyl, ethyl, cyclopropyl, isopropyl and tert·butyl;
• or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture of same.