Salicylic acid derivatives, pharmaceutically acceptable salt thereof, composition thereof and method of use thereof

A compound of formula I:

• or a pharmaceutically acceptable salt, solvate or prodrug thereof,
• wherein each of m and n are independently an integer from 0-3;
• wherein R1 is selected from A1, A2, -(A1)-(A2), -(A2)-(A3), -(A3)-(A2), -(A3)-(A4), -(A5)-(A1)-(A7), -(A5)-(A2)-(A8), -(A5)-(A3)-(A7), and -(A5)-(A6)-L-(A7);
• wherein A1 is C3-6 cycloalkyl, and substituted with 0-3 groups selected from halo, hydroxyl, amino, nitro, cyano, C1-6 haloalkyl, C1-6 polyhaloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 polyhaloalkoxy, C1-6 alkylthio, C1-6 haloalkylthio, C1-6 polyhaloalkylthio, C1-6 alkylamino, C1-6 dialkylamino, (C1-6)-alkyl-(C1-6)-alkoxy, (C1-6)-alkyl-(C1-6)-haloalkoxy, (C1-6)-alkyl-(C1-6)-polyhaloalkoxy, (C1-6)-alkyl-(C1-6)-alkylthio, (C1-6)-alkyl-(C1-6)-haloalkylthio, (C1-6)-alkyl-(C1-6)-polyhaloalkylthio, CO2H, (C═O)R5, (C═O)OR5, and (C═O)NHR5;
• wherein A2 is C3-6 cycloalkyl or heterocycloalkyl, substituted with 0-3 groups selected from halo, hydroxyl, amino, nitro, cyano, C1-6 haloalkyl, C1-6 polyhaloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 polyhaloalkoxy, C1-6 alkylthio, C1-6 haloalkylthio, C1-6 polyhaloalkylthio, C1-6 alkylamino, C1-6 dialkylamino, (C1-6)-alkyl-(C1-6)-alkoxy, (C1-6)-alkyl-(C1-6)-haloalkoxy, (C1-6)-alkyl-(C1-6)-polyhaloalkoxy (C1-6)-alkyl-(C1-6)-alkylthio, (C1-6)-alkyl-(C1-6)-haloalkylthio, (C1-6)-alkyl-(C1-6)-polyhaloalkylthio, CO2H, (C═O)R6, (C═O)OR6, and (C═O)NHR6;
• wherein A3 is aryl, and substituted with 0-3 groups selected from halo, hydroxyl, amino, nitro, cyano, C1-6 haloalkyl, C1-6 polyhaloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 polyhaloalkoxy, C1-6 alkylthio, C1-6 haloalkylthio, C1-6 polyhaloalkylthio, C1-6 alkylamino, C1-6 dialkylamino, (C1-6)- alkyl-(C1-6)-alkoxy, (C1-6)-alkyl-(C1-6)-haloalkoxy, (C1-6)-alkyl-(C1-6)-polyhaloalkoxy, (C1-6)-alkyl-(C1-6)-alkylthio, (C1-6)-alkyl-(C1-6)- haloalkylthio, (C1-6)-alkyl-(C1-6)-polyhaloalkylthio, CO2H, (C═O)R7, (C═O)OR7, and (C═O)NHR7;
• wherein A4 is aryl, and substituted with 1-3 groups selected from halo, hydroxyl, amino, nitro, cyano, C1-6 haloalkyl, C1-6 polyhaloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 polyhaloalkoxy, C1-6 alkylthio, C1-6 haloalkylthio, C1-6 polyhaloalkylthio, C1-6 alkylamino, C1-6 dialkylamino, (C1-6)-alkyl-(C1-6)-alkoxy, (C1-6)-alkyl-(C1-6)-haloalkoxy, (C1-6)-alkyl-(C1-6)-polyhaloalkoxy, (C1-6)-alkyl-(C1-6)-alkylthio, (C1-6)-alkyl-(C1-6)-haloalkylthio, (C1-6)-alkyl-(C1-6)-polyhaloalkylthio, CO2H, (C═O)R8, (C═O)OR8, and (C═O)NHR8;
• wherein A5 is selected from C3-6 cycloalkyl, C3-6 heterocycloalkyl, and aryl, and substituted with 0-3 groups selected from halo, hydroxyl, amino, nitro, cyano, C1-6 haloalkyl, C1-6 polyhaloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 polyhaloalkoxy, C1-6 alkylthio, C1-6 haloalkylthio, C1-6 polyhaloalkylthio, C1-6 alkylamino, C1-6 dialkylamino, (C1-6)-alkyl-(C1-6)-alkoxy, (C1-6)-alkyl-(C1-6)-haloalkoxy, (C1-6)-alkyl-(C1-6)-polyhaloalkoxy, (C1-6)-alkyl-(C1-6)-alkylthio, (C1-6)-alkyl-(C1-6)-haloalkylthio, (C1-6)-alkyl-(C1-6)-polyhaloalkylthio, CO2H, (C═O)R9, (C═O)OR9, and (C═O)NHR9;
• wherein A6 is selected from C3-6 cycloalkyl, C3-6 heterocycloalkyl, and aryl, and substituted with 0-3 groups selected from halo, hydroxyl, amino, nitro, cyano, C1-6 haloalkyl, C1-6 polyhaloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 polyhaloalkoxy, C1-6 alkylthio, C1-6 haloalkylthio, C1-6 polyhaloalkylthio, C1-6 alkylamino, C1-6 dialkylamino, (C1-6)-alkyl-(C1-6)-alkoxy, (C1-6)-alkyl-(C1-6)-haloalkoxy, (C1-6)-alkyl-(C1-6)-polyhaloalkoxy, (C1-6)-alkyl-(C1-6)-alkylthio, (C1-6)-alkyl-(C1-6)-haloalkylthio, (C1-6)-alkyl-(C1-6)-polyhaloalkylthio, CO2H, (C═O)R10, (C═O)OR10, and (C═O)NHR10;
• wherein A7 is selected from C3-6 cycloalkyl, C3-6 heterocycloalkyl, and aryl, and substituted with 0-3 groups selected from halo, hydroxyl, amino, nitro, cyano, C1-6 haloalkyl, C1-6 polyhaloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 polyhaloalkoxy, C1-6 alkylthio, C1-6 haloalkylthio, C1-6 polyhaloalkylthio, C1-6 alkylamino, C1-6 dialkylamino, (C1-6)-alkyl-(C1-6)-alkoxy, (C1-6)-alkyl-(C1-6)-haloalkoxy, (C1-6)-alkyl-(C1-6)-polyhaloalkoxy, (C1-6)-alkyl-(C1-6)-alkylthio, (C1-6)-alkyl-(C1-6)-haloalkylthio, (C1-6)-alkyl-(C1-6)-polyhaloalkylthio, CO2H, (C═O)R11, (C═O)OR11, and (C═O)NHR11;
• wherein A8 is selected from C3-6 cycloalkyl, C3-6 heterocycloalkyl, and aryl, and substituted with 0-3 groups selected from halo, hydroxyl, amino, nitro, C1-6 haloalkyl, C1-6 polyhaloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 polyhaloalkoxy, C1-6 alkylthio, C1-6 haloalkylthio, C1-6 polyhaloalkylthio, C1-6 alkylamino, C1-6 dialkylamino, (C1-6)-alkyl-(C1-6)-alkoxy, (C1-6)-alkyl-(C1-6)-haloalkoxy, (C1-6)-alkyl-(C1-6)-polyhaloalkoxy, (C1-6)-alkyl-(C1-6)-alkylthio, (C1-6)-alkyl-(C1-6)-haloalkylthio, (C1-6)-alkyl-(C1-6)-polyhaloalkylthio, CO2H, (C═O)R12, (C═O)OR12, and (C═O)NHR12;
• wherein L is selected from —(C═O)— and —SO2—;
• wherein each of R5, R6, R7, R8, R9, R10, R11, and R12 is independently selected from hydrogen, C1-6 alkyl, C1-6 haloalkyl, and C1-6 polyhaloalkyl;
• or a pharmaceutically acceptable salt, hydrate, solvate, or polymorph thereof,
• wherein R2 is selected from the group consisting of:
• wherein R3 is selected from the structure represented by formula:
• wherein R4 is a structure represented by formula:
• wherein R13 is selected from the group consisting of —H, —OH, —COR16, —CN, —CH2PO(OH)2, —CH2P(O)3(CH2CH3)2, —NO2, —NHR17, and 1H-tetrazole;
• R16 is selected from the group consisting of:
• —OH, —O—C(1-2)alkyl, —OCH2OC(O)CH3, and —OCH2OC(O)t-Butyl;
• R17 is selected from the group consisting of:
• —H, —C(O)C(O)CH2CH3, —C(O)C(O)OH, and —C(O)CH2-1H-tetrazole;
• R14 is —H or —COOH or when R13 is —COR16 and R16 is OH, R14 is —F, or —OC(O)CH3;
• and
• R15 is H, —OH, or —COOH or when R13 is —COR16 and R16 is OH, R15 is —F, or —OC(O)CH3;
• wherein R13 is —H when R15 is —OH or both R14 and R15 are —COOH, and
• R14 and R15 are —H when R3 is
• and R13 is —OH.