9-aminomethyl substituted tetracycline compounds

A compound of the general formula I:

• or pharmaceutically acceptable salt, prodrug, solvate or isomer thereof,
• wherein
• R2a, R2b, R3, R10, R11 and R12 are each independently hydrogen;
• R5, R6a, R6b and R8 are each independently hydrogen, mercapto, halogen, hydroxy, amino, carboxyl, C1-6alkyl, haloC1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, haloC1-6alkoxy, C1-6alkylthio, C1-6alkylamino, di(C1-6alkyl)amino, hydroxyC1-6alkyl, carboxylC1-6alkyl, aminoC1-6alkyl, C1-6alkylaminoC1-6alkyl, C1-6alkylcarbonyl, C1-6alkylcarbonyloxy, C1-6alkoxycarbonyl, C1-6alkylsulfinyl, C1-6alkylsulfonyl, sulfonic, sulfonylC1-6alkyl, sulfoamino, sulfoaminoC1-6alkyl, C1-6alkylsulfoamino, aminosulfonyl, C1-6alkylaminosulfonyl, di(C1-6alkyl)aminosulfonyl, aminosulfonylC1-6alkyl, C1-6alkylformylamino, C1-6alkylcarbamoyl, di(C1-6alkyl)carbamoyl, carbamoyl, carbamoylC1-6alkyl, 3- to 8-membered cycloalkyl, 6- to 14-membered aryl, 6- to 14-membered aryl-C1-6alkyl, 6- to 14-membered aryl-formyl, 6- to 14-membered aryl-formyloxy, 3- to 8-membered heterocyclyl, 3- to 8-membered heterocyclyl-C1-6alkyl, 6- to 14-membered heteroaryl or 6- to 14-membered heteroaryl-C1-6alkyl;
• R7 is NR7aR7b;
• R4a, R4b, R7a and R7b are each independently hydrogen, C1-6alkyl, haloC1-6alkyl, C2-6alkenyl, C2-6alkynyl, C1-6alkoxy, haloC1-6alkoxy, C1-6alkylthio, hydroxyC1-6alkyl, carboxylC1-6alkyl, aminoC1-6alkyl, C1-6alkylaminoC1-6alkyl, C1-6alkylcarbonyl, C1-6alkoxycarbonyl, C1-6alkylsulfinyl, C1-6alkylsulfonyl, sulfonic, sulfonylC1-6alkyl, sulfoaminoC1-6alkyl, aminosulfonyl, C1-6alkylaminosulfonyl, di(C1-6alkyl)aminosulfonyl, aminosulfonylC1-6alkyl, C1-6alkylcarbamoyl, di(C1-6alkyl)carbamoyl, carbamoyl, carbamoylC1-6alkyl, 3- to 8-membered cycloalkyl, 6- to 14-membered aryl, 6- to 14-membered aryl, 6- to 14-membered aryl-C1-6alkyl, 3- to 14-membered heterocyclyl or 3- to 14-membered heterocyclyl-C1-6alkyl;
• R9a and R9b are each independently:
• (1) hydrogen, provided that R9a and R9b can not be Hydrogen at the same time,
• (2) cyclopropyl, cyclobutyl, 6- to 12-membered spirocyclic group, 6-membered endocyclic group, 8- to 12-membered endocyclic group or 6- to 10-membered saturated fused ring group, the above groups are unsubstituted or substituted by 1 to 3 substituent(s) which may be the same or different and selected from Q1, and carbon(s) in said cyclopropyl, cyclobutyl, 6- to 12-membered spirocyclic group, 6-membered endocyclic group, 8- to 12-membered endocyclic group and 6- to 10-membered saturated fused ring group may be replaced by 1 to 3 atom(s) or group(s) which may be the same or different and selected from O, CO, S, SO, SO2, N and NRc, Rc represents hydrogen or C1-6alkyl;
• (3) cyclobutylC1-6alkyl, cyclopentylC1-6alkyl, 6- to 12-membered spirocyclic group C1-6alkyl, 6- to 9-membered endocyclic group C1-6alkyl or 6- to 10-membered saturated fused ring group C1-6alkyl, the above groups are unsubstituted or substituted by 1 to 3 substituent(s) which may be the same or different and selected from Q1, and carbon(s) in said cyclobutyl, 6- to 12-membered spirocyclic group and 6- to 9-membered endocyclic group may be replaced by 1 to 3 atom(s) or group(s) which may be the same or different and selected from O, CO, S, SO, SO2, N and NRc, and carbon(s) in said 6- to 10-membered saturated fused ring group may be replaced by 1 to 3 atom(s) or group(s) which may be the same or different and selected from CO, S, SO, SO2, N and NRc, Rc represents hydrogen or C1-6alkyl;
• Alternatively, R9a and R9b together with the nitrogen atom to which they are attached form azetidinyl, 6- to 9-membered spirocyclic group or 6- to 9-membered saturated fused ring group, the above groups are unsubstituted or substituted by 1 to 3 Q2 substituent(s) which may be the same or different, and carbon(s) in said azetidinyl, 6- to 9-membered spirocyclic group and 6- to 9-membered saturated fused ring group may be replaced by 1 to 3 atom(s) or group(s) which may be the same or different and selected from O, CO, S, SO, SO2, N and NRc, Rc represents hydrogen or C1-6alkyl;
• Q1 and Q2 are independently selected from halogen, hydroxy, amino, carboxyl, C1-6alkyl, C1-6alkoxy, haloC1-6alkyl, haloC1-6alkoxy, hydroxyC1-6alkyl, aminoC1-6alkyl, carboxylC1-6alkyl, C1-6alkylamino, di(C1-6alkyl)amino, aminosulfonyl, aminosulfonylC1-6alkyl, carbamoyl, carbamoylC1-6alkyl, C1-6alkylcarbonyl, C1-6alkylcarbonyloxy, C1-6alkoxycarbonyl, phenyl, 3- to 8-membered cycloalkyl or 3- to 8-membered heterocyclyl;
• R13a and R13b are each independently hydrogen, C1-6alkyl or 3- to 8-membered cycloalkyl.