Novel n-acyl-arylsulfonamide derivatives as aminoacyl-trna synthetase inhibitors

At least one chemical entity selected from a compound of Formula I:

• enantiomers, diastereomers, tautomers or pharmaceutically acceptable salts thereof, wherein:
• R1 represents C1-4alkyl;
• R2 represents C1-4alkyl or H;
• R3 represents C1-4alkyl or H;
• R1, R2 or R1, R3 together with the atoms to which they are attached may form one of 3-membered to 6-membered rings;
• provided that R2 and R3 are not both hydrogen;
• provided that R1, R2 and R3 do not form a cycle together with L1 or L5
• L1 is independently C—R4 or N;
• L2 is independently C—R5 or N;
• L3 is independently C—R6 or N;
• L4 is independently C—R7 or N;
• L5 is independently C—R8 or N;
• R4 is independently H, halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C5-9heteroaryl, C6-10carboaryl, C3-6cycloalkyl, C1-5heterocyclyl, CN, C(═O)Ra, C(═O)ORa, C(═O)N(Ra)Rb, ORa, OC(═O)Ra, OC(═O)N(Ra)Rb, N(Ra)Rb, N(Ra)S(O)0-2Rb, N(Ra)C(═O)Rb, N(Ra)C(═O)ORb, S(O)0-2Ra, S(O)0-2N(Ra)Rb, wherein said alkyl, alkenyl, alkynyl, carboaryl, heteroaryl, cycloalkyl and heterocyclyl are optionally substituted by 1 to 5 substituents independently selected from ORa, N(Ra)Rb, oxo, halo, S(O)0-2Ra and S(O)0-2N(Ra)Rb;
• R5 is independently H, halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C5-9heteroaryl, C6-10carboaryl, C3-6cycloalkyl, C1-5heterocyclyl, CN, C(═O)Ra, C(═O)ORa, C(═O)N(Ra)Rb, ORa, OC(═O)Ra, OC(═O)N(Ra)Rb, S(O)0-2Ra, S(O)0-2N(Ra)Rb, wherein said alkyl, alkenyl, alkynyl, carboaryl, heteroaryl, cycloalkyl and heterocyclyl are optionally substituted by 1 to 5 substituents independently selected from ORa, N(Ra)Rb, oxo, halo, S(O)0-2Ra and S(O)0-2N(Ra)Rb;
• or
• R4 and R5 taken together with the atoms to which they are attached form a C4-6heterocyclic ring, C4-6 carbocyclic ring, C6 aromatic ring or C5-6heteroaromatic ring optionally substituted by halogen, C(═O)N(Ra)Rb, oxo, ORa, N(Ra)Rb or C1-3alkyl;
• R6 is independently H, halo, C2-6alkyl, C2-6alkenyl, C2-6alkynyl, C5-9heteroaryl, C6-10carboaryl, C3-6cycloalkyl, C1-5heterocyclyl, CN, C(═O)Ra, C(═O)ORa, C(═O)N(Ra)Rb, ORa, OC(═O)Ra, OC(═O)N(Ra)Rb, S(O)0-2Ra, S(O)0-2N(Ra)Rb, wherein said alkyl, alkenyl, alkynyl, carboaryl, heteroaryl, cycloalkyl and heterocyclyl are optionally substituted by 1 to 5 substituents independently selected from ORa, N(Ra)Rb, oxo, halo, S(O)0-2Ra and S(O)0-2N(Ra)Rb;
• or
• R5 and R6 taken together with the atoms to which they are attached form a C4-6heterocyclic ring, C4-6 carbocyclic ring, C6 aromatic ring or C5-6heteroaromatic ring optionally substituted by halogen, C(═O)N(Ra)Rb, oxo, ORa, N(Ra)Rb or C1-3alkyl;
• R7 is independently H, halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C5-9heteroaryl, C6-10carboaryl, C3-6cycloalkyl, C1-5heterocyclyl, CN, C(═O)Ra, C(═O)ORa, C(═O)N(Ra)Rb, ORa, OC(═O)Ra, OC(═O)N(Ra)Rb, S(O)0-2Re, S(O)0-2N(Ra)Rb, wherein said alkyl, alkenyl, alkynyl, carboaryl, heteroaryl, cycloalkyl and heterocyclyl are optionally substituted by 1 to 5 substituents independently selected from ORa, N(Ra)Rb, oxo, halo, S(O)0-2Ra and S(O)0-2N(Ra)Rb
• R8 is independently H, halo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C5-9heteroaryl, C6-10carboaryl, C3-6cycloalkyl, C1-5heterocyclyl, CN, C(═O)Ra, C(═O)ORa, C(═O)N(Ra)Rb, ORa, OC(═O)Ra, OC(═O)N(Ra)Rb, N(Ra)Rb, N(Ra)S(O)0-2Rb, N(Ra)C(═O)Rb, N(Ra)C(═O)ORb, S(O)0-2Ra, S(O)0-2N(Ra)Rb, wherein said alkyl, alkenyl, alkynyl, carboaryl, heteroaryl, cycloalkyl and heterocyclyl are optionally substituted by 1 to 5 substituents independently selected from ORa, N(Ra)Rb, oxo, halo, S(O)0-2Ra and S(O)0-2N(Ra)Rb;
• Ra and Rb are independently H, C1-6alkyl, C5-6heteroaryl or C6carboaryl, wherein each alkyl, heteroaryl or aryl are optionally substituted by 1 to 3 substituents selected from oxo, halo, NH2, OH.