Viral polymerase inhibitors

An isomer, enantiomer, diastereoisomer, or tautomer of a compound, represented by formula I:

• wherein
• - - - represents either a single or a double bond;
• B is —N— and A is ═CR1— or ═N—;
• or
• B is ═C— and A is O, S or NR1;
• R1 is selected from the group consisting of:
• H, (C1-6)alkyl optionally substituted with:
• halogen, OR11, SR11 or N(R12)2, wherein R11 and each R12 is independently H, (C1-6)alkyl, (C3-7)cycloalkyl, (C1-6)alkyl-(C3-7)cycloalkyl, (C1-6)alkyl-aryl or (C1-6)alkyl-Het, said aryl or Het optionally substituted with R160;
• or
• both R12 are covalently bonded together and to the nitrogen to which they are both attached to form a 5, 6 or 7-membered saturated heterocycle;
• the group —C(═Y1)-Z is covalently linked to either M2 or M3,
• M1 is CR4a,
• M2 or M3, when not linked to —C(═Y1)-Z, is CR5,
• M4 is CR4b,
• and in addition one or two of the groups selected from M1, M2, M3 and M4 may also be N, with the proviso that the group M2 or M3 to which —C(═Y1)-Z is linked is a C-atom,
• Y1 is O or S;
• Z is defined as NRN2—SO2—C or NRN3SO2—N(RN2)RN1, wherein RC, RN1 or any heterocycle formed by RN1 and RN2 is optionally substituted with R60;
• R2 is selected from:
• halogen or R21, wherein R21 is aryl or Het, said R21 is optionally substituted with R150;
• R3 is selected from (C1-6)alkyl, (C3-7)cycloalkyl, (C1-3)alkyl-(C3-7)cycloalkyl, (C5-7)cycloalkenyl, (C1-3)alkyl-(C5-7)cycloalkenyl, (C6-10)bicycloalkyl, (C1-3)alkyl-(C6-10)bicycloalkyl, (C6-10)bicycloalkenyl, (C1-3)alkyl-(C6-10)bicycloalkenyl, HCy or (C1-3)alkyl-HCy,
• wherein HCy is a saturated or unsaturated 4 to 7-membered heterocyclic group with 1 to 3 heteroatoms selected from O, S and N;
• said alkyl, cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl, HCy and alkyl-HCy being optionally substituted with from 1 to 4 substituents selected from:
• a) halogen;
• b) (C1-6)alkyl optionally substituted with:
• 1 to 3 substituents selected from halogen;
• OR31 or SR31 wherein R31 is H, (C1-6)alkyl, (C3-7)cycloalkyl or (C1-3)alkyl-(C3-7)cycloalkyl;
• or
• N(R32)2 wherein each R32 is independently H, (C1-6)alkyl, (C3-7)cycloalkyl or (C1-3)alkyl-(C3-7)cycloalkyl;
• or both R32 are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle;
• c) OR33 or SR33 wherein R33 is H, (C1-6)alkyl, (C3-7)cycloalkyl or (C1-3)alkyl-(C3-7)cycloalkyl;
• d) N(R35)2 wherein each R35 is independently H, (C1-6)alkyl, (C3-7)cycloalkyl or (C1-3)alkyl-(C3-7)cycloalkyl;
• or both R35 are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle;
• R4a, R4b, R5 each are independently H or defined as R150;
• R60 is defined as 1 to 4 substituents independently selected from:
• 1 to 3 substituents selected from halogen;
• one of each substituent selected from:
• OPO3H, NO2, cyano, azido, C(═NH)NH2, C(═NH)NH(C1-6)alkyl or C(═NH)NHCO(C1-6)alkyl, SO3H;
• and
• 1 to 3 substituents selected from:
• a) (C1-6) alkyl, (C3-7)cycloalkyl, (C3-7) spirocycloalkyl optionally containing 1 or 2 heteroatoms selected from N, O and S;
• (C2-6)alkenyl, (C2-8)alkynyl, (C1-6)alkyl-(C3-7)cycloalkyl, all of which optionally being substituted with R150;
• b) ORO;
• c) OC(O)RO;
• d) SRO, SO2RC, SO2N(RN2)RN1, SO2N(RN2)C(O)RC, CONRN3SO2N(RN2)RN1, or CONRN2SO2RC;
• e) N(RN2)RN1, N(RN2)COORC, N(RN2)SO2RC or N(RN1)ORO;
• f) N(RN2)CORC;
• g) N(RN3)CON(RN2)RN1;
• h) N(RN3)COCORC, N(RN3)COCOORO, N(RN3)COCON(RN2)ORO, or N(RN3)COCON(RN2)RN1;
• i) CORO;
• j) COORO;
• k) CON(RN2)RN1;
• l) aryl, Het, (C1-4)alkyl-aryl or (C1-4)alkyl-Het, all of which optionally being substituted with R150.
• wherein said RN1, RC and/or RO are optionally substituted with R150 as defined,
• R150 is defined as 1 to 4 substituents independently selected from:
• 1 to 3 substituents selected from halogen;
• one of each substituent selected from:
• OPO3H, NO2, cyano, azido, SO3H C(═NH)NH2, C(═NH)NH(C1-6)alkyl or C(═NH)NHCO(C1-6)alkyl;
• and
• 1 to 3 substituents selected from:
• a) (C1-6)alkyl, (C3-7)cycloalkyl, (C3-7)spirocycloalkyl optionally containing 1 or 2 heteroatoms selected from N, O and S;
• (C2-6)alkenyl, (C2-8)alkynyl, (C1-3)alkyl-(C3-7)cycloalkyl, all of which optionally substituted with R160;
• b) ORO;
• c) OC(O)RO;
• d) SRO, SO2RC, SO2N(RN2)RN1 or SO2N(RN2)C(O)RC;
• e) N(RN2)RN1, N(RN2)COORC, N(RN2)SO2RC or N(RN1)ORO;
• f) N(RN2)CORC;
• g) N(RN3)CON(RN2)RN1;
• h) N(RN3)COCORC, N(RN3)COCOORO, N(RN3)COCON(RN2)OH, N(RN3)COCON(RN2)O(C1-4)alkyl or N(RN3)COCON(RN2)RN1;
• i) CORO;
• j) COORO;
• k) tetrazole, triazole, CONRN2SO2RC, CONRN3—SO2N(RN2)RN1 or CON(RN2)RN1;
• wherein said RN1, RC and/or RO are optionally substituted with R160 as defined;
• R160 is defined as 1, 2 or 3 substituents independently selected from:
• 1, 2 or 3 fluorine substituents;
• and
• one of each substituent selected from tetrazole, triazole, chlorine, bromine, iodine, CN, nitro, (C1-4)alkyl, OCF3, SCF3, CF3, COOR161, SO3H, SR161, SO2R163, OR161, N(R162)2, SO2N(R162)2, SO2NR162COR162, NR162SO2R163, —NR161—CO—COOR161, —NR161—CO—CO(NR162)2, —CONR161SO2RC, CONR161—SO2N(R162)2 or —SO2—NR161—CORC, NR162COR162 or CON(R162)2, wherein R161, R163 and each R162 is independently (C1-4)alkyl, (C3-7)cycloalkyl or (C1-3)alkyl-(C3-7)cycloalkyl;
• and R161 and each R162 may each independently also be H;
• or both R162 are covalently bonded together and to the nitrogen to which they are attached to form a 5, 6 or 7-membered saturated heterocycle;
• RO, RC are independently defined as (C1-6)alkyl, (C3-7)cycloalkyl, (C1-4)alkyl-(C3-7)cycloalkyl, (C2-6)alkenyl, aryl, Het, (C1-4)alkyl-aryl, or (C1-4)alkyl-Het;
• or
• RO is also optionally defined as H.
• RN1 is H, (C1-6)alkyl, (C3-7)cycloalkyl, (C1-4)alkyl-(C3-7)cycloalkyl, (C2-6)alkenyl, aryl, Het, (C1-4)alkyl-aryl, (C1-4)alkyl-Het;
• and
• RN2, RN3, RN4 are independently H, CH3, (C2-6)alkyl, (C3-6)cycloalkyl, (C1-4)alkyl-(C3-6)cycloalkyl;
• all of which being optionally substituted with halogen, carboxy or (C1-6)alkoxycarbonyl;
• and/or wherein said alkyl, cycloalkyl or alkylcycloalkyl is optionally substituted with hydroxy, (C1-6)alkyl, (C1-6)alkoxy, amino, —NH(C1-4)alkyl and/or —N((C1-4)alkyl)2;
• or
• in the case
• a) of a group N(RN2)RN1 the substituents RN2 and RN1;
• or
• b) of a group NRN3—N(RN2)RN1 the substituents RN3 and RN1, or RN2 and RN1;
• may be covalently bonded together to form a 4-, 5-, 6- or 7-membered saturated or unsaturated N-containing heterocycle or a 8-, 9-, 10- or 11-membered N-containing heterobicycle, each optionally having additionally from 1 to 3 heteroatoms selected from O, N, and S;
• wherein Het is defined as a 4-, 5-, 6- or 7-membered heterocycle having 1 to 4 heteroatoms selected from O, N and S, or a 8-, 9-, 10- or 11-membered heterobicycle having 1 to 5 heteroatoms selected from O, N and S;
• or a salt thereof.