Macrocyclic inhibitors of flaviviridae viruses

A compound of Formula I:

• or a pharmaceutically acceptable salt, isotope, stereoisomer, mixture of stereoisomers, tautomer, ester or prodrug thereof, wherein:
• A is CH2;
• A1 is (C2-C5)alkenylene, wherein a sp3 carbon atom of A1 is optionally replaced by —O—, —S(O)n—, —NH— or —N((C1-C4)alkyl)-, and wherein a sp3 or sp2 carbon atom of A1 is optionally substituted with one or more groups selected from the group consisting of halo, (C1-C5)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, aryl, heterocycloalkyl, cycloalkyl, aryl(C1-C4)alkyl, cycloalkyl(C1-C4)alkyl, heterocycloalkyl(C1-C4)alkyl, arylheterocycloalkyl(C1-C4)alkyl, —OR9, —SR9, —S(O)R9, —S(O)2R9 and —N(R9)2;
• A2 is —CH(R8)-heteroarylene, wherein A2 is optionally substituted with one or more substituents selected from the group consisting of —OR9, —SR9, —S(O)R9, —S(O)2R9, —N(R9)2, halo, halo(C1-C4)alkyl, halo(C1-C4)alkoxy, cyano and (C1-C8)alkyl;
• L1 is —O—C(O);
• X1 is —NH— or —N(CH3)—;
• R1 and R2, when taken together with the carbon to which they are both attached, form —C(═O)—;
• R3 is H or (C1-C4)alkyl optionally substituted with halo, cyano, hydroxyl or (C1-C4)alkoxy;
• R4a and R4b are independently H or (C1-C5)alkyl, wherein each R4a and R4b is optionally substituted with one or more substituents selected from the group consisting of cyano, —COOH, halo, hydroxyl, amino, (C1-C5)alkoxy, mono(C1-C5)alkylamino, di(C1-C5)alkylamino, aryl and heteroaryl;
• R5a and R5b are independently H or (C1-C5)alkyl optionally substituted with one or more substituents selected from the group consisting of —N3, cyano, —COOH, halo, hydroxyl, amino, mono(C1-C5)alkylamino, di(C1-C5)alkylamino, (C1-C5)alkoxy, aryl and heteroaryl, or
• R5a and R5b together form a spirocycle having Formula (a):
• wherein one or more carbon ring atoms of Formula (a) is optionally replaced by a nitrogen, oxygen or sulfur atom, and wherein a ring atom of Formula (a) optionally has one or more substituents selected from the group consisting of oxo, ═N(C1-C4)alkoxy, halo, hydroxyl, —NH2, (C1-C4)alkyl, halo(C1-C4)alkyl, (C1-C4)alkoxy, —OC(O)R9, —C(O)2R9, and —S(O)2R9;
• R6a and R6b together form a spirocycle having Formula (a);
• R8 is H, (C1-C4)alkyl, halo(C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, aryl, heteroaryl, heterocycloalkyl or cycloalkyl, wherein R8 is optionally substituted with —OR, —N(R9)2, —CON(R9)2, or cyano;
• each R9 is independently H, (C1-C4)alkyl, halo(C1-C4)alkyl, (C2-C4)alkenyl or (C2-C4)alkynyl;
• and
• m is 1, 2, 3, 4 or 5.