Benzimidazole analogues for the treatment or prevention of flavivirus infections

A compound of formula (IIB):

• or pharmaceutically acceptable salts thereof, wherein
• each A is independently C6-14 aryl, 4-12 membered heterocycle, C3-10 cycloalkyl, or 5-12 membered heteroaryl;
• B and B′ are each independently absent, C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl;
• R1 is halogen, —ORa, —NRaRb, —C(═O)ORa, —C(O)NRaRb, —C(═O)OH, —C(═O)Ra, —C(═NORc)Ra, —C(═NRc)NRaRb, —NRdC(═O)NRaRb, —NRbC(═O)Ra, —NRdC(═NRc)NRaRb, —NRbC(═O)ORa, —OC(═O)NRaRb, —OC(═O)Ra, —OC(═O)ORa, hydroxyl, nitro, azido, cyano, —S(O)0-3Ra, —SO2NRaRb, —NRbSO2Ra, —NRbSO2NRaRb, —P(═O)ORaORb, C1-6 alkyl which is unsubstituted or substituted one or more times by R10, C2-6 alkenyl which is unsubstituted or substituted one or more times by R10, C2-6 alkynyl which is unsubstituted or substituted one or more times by R10, or any two occurrences of R1 can be taken together with the atoms to which they are attached to form a 5-7 cycloalkyl which is unsubstituted or substituted one or more times by R11 or a 5-7 membered heterocycle which is unsubstituted or substituted one or more times by R12;
• Ra-Rd are each independently H, C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, C6-12 aryl, C7-16 aralkyl, 5-12 membered heteroaryl, 6-18 membered heteroaralkyl, 3-12 membered heterocycle, or 4-18 membered heterocycle-alkyl;
• R2′, and R2 are each independently halogen, C1-10 alkyl, C1-6 halogenated alkyl, —(CH2)1-6OH, —ORa, —C(═O)ORa, NRaRb, —NRbC(═O)Ra, —C(O)NRaRb, —S(O)0-3Ra, C6-12 aryl, or 5-12 membered heteroaryl;
• R3 and R3′ are each independently H, C1-18 alkyl which is unsubstituted or substituted one or more times by R10, C2-12 alkenyl which is unsubstituted or substituted one or more times by R10, C2-12 alkynyl which is unsubstituted or substituted one or more times by R10, C6-14 aryl which is unsubstituted or substituted one or more times by R11, C2-16 aralkyl which is unsubstituted or substituted one or more times by R11, 5-12 membered heteroaryl which is unsubstituted or substituted one or more times by R11, 6-18 membered heteroaralkyl which is unsubstituted or substituted one or more times by R11, 3-12 membered heterocycle which is unsubstituted or substituted one or more times by R12, or 4-18 membered heterocycle-alkyl which is unsubstituted or substituted one or more times by R12;
• X and Y are each independently
• or a bond;
• wherein the asterisk (*) indicates the point of attachment to the nitrogen of ring C or C′;
• R4 is H, C1-6 alkyl, or halogenated C1-6 alky;
• R5 and R5′ are each independently halogen, —NRaRb, —C(O)NRaRb, —(CH2)1-6OH, C1-6 alkyl, C1-6 halogenated alkyl, hydroxyl, C6-14 aryl, or C1-6 alkoxy;
• wherein two occurrence of R4 can be taken together with the atoms to which they are attached to form a C1-6 alkenyl which is unsubstituted or substituted one or more times by R10, a 3-7 cycloalkyl which is unsubstituted or substituted one or more times by R11 or a 4-7 membered heterocycle which is unsubstituted or substituted one or more times by R12, wherein two occurrence of R4′ can be taken together with the atoms to which they are attached to form a C1-6 alkenyl which is unsubstituted or substituted one or more times by R10, a 3-7 cycloalkyl which is unsubstituted or substituted one or more times by R11 or a 4-7 membered heterocycle which is unsubstituted or substituted one or more times by R12, wherein Ra-Rb are each independently H, C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, C6-12 aryl, C2-16 aralkyl, 5-12 membered heteroaryl, 6-18 membered heteroaralkyl, 3-12 membered heterocycle, or 4-18 membered heterocycle-alkyl;
• R6 and R6′ are each independently H, C1-6 alkyl, —(CH2)1-6OH, C2-6 alkenyl, or C2-6 alkynyl;
• m, and n, combined are 1, 2, 3 or 4;
• p is 0, 1, 2, 3 or 4;
• q′ is 0, 1 or 2;
• q and r are each independently 0, 1, 2, 3 or 4;
• R10 is halogen, —ORa, oxo, NRaRb, ═NO—Rc, —C(═O)ORa, —C(O)NRaRb, —C(═O)OH, —C(═O)Ra, —C(═NORc)Ra, —C(═NRc)NRaRb, —NRdC(═O)NRaRb, —NRbC(═O)Ra, —NRdC(═NRc)NRaRb, —NRbC(═O)ORa, —OC(═O)NRaRb, —OC(═O)Ra, —OC(═O)ORa, hydroxyl, nitro, azido, cyano, —S(O)0-3Ra, —SO2NRaRb, —NRbSO2Ra, —NRbSO2NRaRb, or —P(═O)ORaORb;
• R11 is halogen, —ORa, —NRaRb, —C(═O)ORa, —C(O)NRaRb, —C(═O)OH, —C(═O)Ra, —C(═NORc)Ra, —C(═NRc)NRaRb, —NRdC(═O)NRaRb, —NRbC(═O)Ra, —NRdC(═NRc)NRaRb, —NRbC(═O)ORa, —OC(═O)NRaRb, —OC(═O)Ra, —OC(═O)ORa, hydroxyl, nitro, azido, cyano, —S(O)0-3Ra, —SO2NRaRb, —NRbSO2Ra, —NRbSO2NRaRb, or —P(═O)ORaORb, C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, C6-12 aryl, C7-16 aralkyl, 5-12 membered heteroaryl, 6-18 membered heteroaralkyl, 3-12 membered heterocycle, or 4-18 membered heterocycle-alkyl;
• and
• R12 is halogen, —ORa, oxo, NRaRb, ═NO—Rc, —C(═O)ORa, —C(O)NRaRb, —C(═O)OH, —C(═O)Ra, —C(═NORc)Ra, —C(═NRc)NRaRb, —NRdC(═O)NRaRb, —NRbC(═O)Ra, —NRdC(═NRc)NRaRb, —NRbC(═O)ORa, —OC(═O)NRaRb, —OC(═O)Ra, —OC(═O)ORa, hydroxyl, nitro, azido, cyano, —S(O)0-3Ra, —SO2NRaRb, —NRbSO2Ra, —NRbSO2NRaRb, or —P(═O)ORaORb, C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, C6-12 aryl, C7-16 aralkyl, 5-12 membered heteroaryl, 6-18 membered heteroaralkyl, 3-12 membered heterocycle, or 4-18 membered heterocycle-alkyl.