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:
• A1 is (C2-C5)alkylene, (C2-C5)alkenylene, (C2-C5)alkynylene, —O—(C2-C4)alkylene, —O—(C2-C4)alkenylene, arylene, aryl(C1-C2)alkylene, heterocycloalkylene, pyrazolylene, pyridylene, pyrimidinylene or heterocycloalkyl(C1-C2)alkylene, wherein a sp3 carbon atom of A1 is optionally substituted with one or more (C1-C4)alkyl;
• A2 is arylene or heteroarylene, wherein A2 is optionally substituted with halo;
• X1 is —O—, —NH— or —N((C1-C4)alkyl)-;
• R1a and R1b are independently H, (C1-C4)alkyl, (C2-C4)alkenyl or (C2-C4)alkynyl;
• R2 is H, (C1-C4)alkyl, (C2-C4)alkenyl or (C2-C4)alkynyl;
• R3a and R3b are independently H or (C1-C8)alkyl;
• R4a and R4b are independently H, —OH, (C1-C4)alkoxy, halo(C1-C4)alkoxy or (C1-C8)alkyl;
• R5 is H, (C1-C4)alkyl, (C2-C4)alkenyl or (C2-C4)alkynyl, or
• R5 forms a cyclic moiety along with —N((C1-C4)alkyl)- of X1 or arylene of A2;
• and
• R6 is H or (C1-C4)alkyl.