Inhibitors of Flaviviridae viruses

A compound of Formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is selected from the group consisting of optionally substituted C1-12 alkyl, optionally substituted C2-12 alkenyl, optionally substituted C2-12 alkynyl, optionally substituted C3-12 cycloalkyl, optionally substituted C6-14 aryl, optionally substituted 3-14 membered heteroaryl, optionally substituted 3-12 membered heterocyclyl, optionally substituted 3-18 membered heteroarylalkyl, optionally substituted 3-18 membered heterocyclylalkyl and optionally substituted C6-18 arylalkyl, wherein, each substituted R1 is substituted with one or more Q1;
• each Q1 is independently selected from the group consisting of
• halogen, oxo, oxide, —NO2, —N(═O), —SR10, —S(O)R10, —S(O)2R10, —S(O)2NR10R11, —NR10C(O)R11, —NR10C(O)NR11R12, —NR10S(O)R11, —NR10S(O)2R11, —OP(O)R11R12, —P(O)R11R12, —P(O)OR11R12, —P(O)(OR11)OR12, —C(O)NR11R12, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted C3-6 cycloalkyl, optionally substituted C6-12 arylalkyl, optionally substituted C6-12 aryl, optionally substituted 3-14 membered heteroaryl, optionally substituted C1-6 alkyloxy, optionally substituted C2-6 alkenyloxy, optionally substituted C2-6 alkynyloxy, optionally substituted C3-6 cycloalkyloxy, optionally substituted C6-12 aryloxy, optionally substituted 3-14 membered heteroaryloxy, optionally substituted 4-12 membered heterocyclyloxy, optionally substituted —C(O)C1-6 alkyl, optionally substituted —C(O)C2-6 alkenyl, optionally substituted —C(O)C2-6 alkynyl, optionally substituted —C(O)C3-6 cycloalkyl, optionally substituted —C(O)C6-12 aryl, optionally substituted —C(O)-3-14 membered heteroaryl, optionally substituted —C(O)C6-12 arylalkyl, optionally substituted -3-10 membered heterocyclyl, —OH, —NR11R12, —C(O)OR10, —CN, —N3, —C(═NR13)NR11R12, —C(═NR13)OR10, —NR10C(═NR13)NR11R12, —NR11C(O)OR10, and —OC(O)NR11R12;
• each R10, R11, and R12, independently, is selected from the group consisting of H, optionally substituted C1-12 alkyl, optionally substituted C2-12 alkenyl, optionally substituted C2-12 alkynyl, optionally substituted C3-12 cycloalkyl, optionally substituted
• C6-14 aryl, optionally substituted 3-14 membered heteroaryl, optionally substituted 3-12 membered heterocyclyl, optionally substituted 3-18 membered heteroarylalkyl, and optionally substituted C6-18 arylalkyl;
• or R11 and R12 taken together with the atoms to which they are attached form a 3 to 10 membered heterocyclyl;
• each R13, independently, is selected from the group consisting of H, optionally substituted C1-12 alkyl, optionally substituted C2-12 alkenyl, optionally substituted C2-12 alkynyl, optionally substituted C3-12 cycloalkyl, optionally substituted C6-14 aryl, optionally substituted 3-14 membered heteroaryl, optionally substituted 3-12 membered heterocyclyl, optionally substituted 3-18 membered heteroarylalkyl, optionally substituted C6-18 arylalkyl, —CN, —C(O)R14, —CHO and —S(O)2R14;
• each R14, independently, is optionally substituted C1-12 alkyl;
• wherein, each substituted Q1, substituted R10, substituted R11, substituted R12, substituted R13, or substituted R14 is independently substituted with one or more Q6;
• R2 is selected from the group consisting of optionally substituted C1-12 alkyl, optionally substituted C2-12 alkenyl, optionally substituted C2-12 alkynyl, optionally substituted C3-12 cycloalkyl, optionally substituted C6-14 aryl, optionally substituted 3-14 membered heteroaryl, optionally substituted 3-12 membered heterocyclyl, optionally substituted 3-18 membered heteroarylalkyl, and optionally substituted C6-18 arylalkyl;
• wherein, each substituted R2 is substituted with one or more Q2;
• each Q2, independently, is selected from the group consisting of
• halogen, oxo, oxide, —NO2, —N(═O), —SR20, —S(O)R20, —S(O)2R20, —S(O)2NR20R21, —NR20C(O)R21, —NR20C(O)NR21R22, —NR20S(O)R21, —NR20S(O)2R21, —OP(O)R21R22, —P(O)R21R22, —P(O)OR21R22, —P(O)(OR21)OR22, —C(O)NR21R22, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted C3-6 cycloalkyl, optionally substituted C6-12 arylalkyl, optionally substituted C6-12 aryl, optionally substituted 3-14 membered heteroaryl, optionally substituted C1-6 alkyloxy, optionally substituted C2-6 alkenyloxy, optionally substituted C2-6 alkynyloxy, optionally substituted C3-6 cycloalkyloxy, optionally substituted C6-12 aryloxy, optionally substituted 3-14 membered heteroaryloxy, optionally substituted 4-12 membered heterocyclyloxy, optionally substituted —C(O)C1-6 alkyl, optionally substituted —C(O)C2-6 alkenyl, optionally substituted —C(O)C2-6 alkynyl, optionally substituted —C(O)C3-6 cycloalkyl, optionally substituted —C(O)C6-12 aryl, optionally substituted —C(O)-3-14 membered heteroaryl, optionally substituted —C(O)C6-12 arylalkyl, optionally substituted 3-10 membered heterocyclyl, —OH, —NR21R22, —C(O)OR20, —CN, —N3, —C(═NR23)NR21R22, —C(═NR23)OR20, —NR20C(═NR23)NR21R22, NR21C(O)OR20, and —OC(O)NR21R22;
• each R20, R21, and R22, independently, is selected from the group consisting of H, optionally substituted C1-12 alkyl, optionally substituted C2-12 alkenyl, optionally substituted C2-12 alkynyl, optionally substituted C3-12 cycloalkyl, optionally substituted C6-14 aryl, optionally substituted 3-14 membered heteroaryl, optionally substituted 3-12 membered heterocyclyl, optionally substituted 3-18 membered heteroarylalkyl, and optionally substituted C6-18 arylalkyl;
• or R21 and R22 taken together with the atoms to which they are attached form a 3 to 10 membered heterocyclyl;
• each R23, independently, is selected from the group consisting of H, optionally substituted C1-12 alkyl, optionally substituted C2-12 alkenyl, optionally substituted C2-12 alkynyl, optionally substituted C3-12 cycloalkyl, optionally substituted C6-14 aryl, optionally substituted 3-14 membered heteroaryl, optionally substituted 3-12 membered heterocyclyl, optionally substituted 3-18 membered heteroarylalkyl, optionally substituted C6-18 arylalkyl, —CN, —C(O)R24, —CHO and —S(O)2R24;
• each R24 individually is optionally substituted C1-12 alkyl;
• wherein, each substituted Q2, substituted R20, substituted R21, substituted R22, substituted R23, or substituted R24 is independently substituted with one or more Q6;
• Y is —R3-L-Het, —N(R4)(R5) or —R6═NOR7;
• R3 is selected from the group consisting of optionally substituted C1-12 alkylene, C2-12 alkenylene, substituted C2-12 alkenylene, C2-12 alkynylene, substituted C2-12 alkynylene, C3-12 cycloalkylene, substituted C3-12 cycloalkylene, C3-12 cycloalkylalkylene, substituted C3-12 cycloalkylalkylene, optionally substituted C6-14 arylene, optionally substituted 3-14 membered heteroarylene, optionally substituted 3-12 membered heterocyclylene, optionally substituted 3-18 membered heteroarylalkylene, and optionally substituted C6-18 arylalkylene;
• wherein each substituted R3 is substituted with one or more Q3;
• each Q3, independently, is selected from the group consisting of
• halogen, oxo, oxide, —NO2, —N(═O), —SR30, —S(O)R30, —S(O)2R30, —S(O)2NR30R31, —NR30C(O)R31, —NR30C(O)NR31R32, —NR30S(O)R31, —NR30S(O)2R31, —OP(O)R31R32, —P(O)R31R32, —P(O)OR31R32, —P(O)(OR31)OR32, —C(O)NR31R32, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted C3-6 cycloalkyl, optionally substituted C6-12 arylalkyl, optionally substituted C6-12 aryl, optionally substituted 3-14 membered heteroaryl, optionally substituted C1-6 alkyloxy, optionally substituted C2-6 alkenyloxy, optionally substituted C2-6 alkynyloxy, optionally substituted C3-6 cycloalkyloxy, optionally substituted C6-12 aryloxy, optionally substituted 3-14 membered heteroaryloxy, optionally substituted 4-12 membered heterocyclyloxy, optionally substituted —C(O)C1-6 alkyl, optionally substituted —C(O)C2-6 alkenyl, optionally substituted —C(O)C2-6 alkynyl, optionally substituted —C(O)C3-6 cycloalkyl, optionally substituted —C(O)C6-12 aryl, optionally substituted —C(O)-3-14 membered heteroaryl, optionally substituted —C(O)C6-12 arylalkyl, optionally substituted 3-10 membered heterocyclyl, —OH, —NR31R32, —C(O)OR30, —CN, —N3, —C(═NR33)NR31R32, —C(═NR33)OR30, —NR30C(═NR33)NR31R32, —NR31C(O)OR30, and —OC(O)NR31R32;
• each R30, R31, and R32, independently is selected from the group consisting of H, optionally substituted C1-12 alkyl, optionally substituted C2-12 alkenyl, optionally substituted C2-12 alkynyl, optionally substituted C3-12 cycloalkyl, optionally substituted C6-14 aryl, optionally substituted 3-14 membered heteroaryl, optionally substituted 3-12 membered heterocyclyl, optionally substituted 3-18 membered heteroarylalkyl, and optionally substituted C6-18 arylalkyl;
• or R31 and R32 taken together with the atoms to which they are attached form a 3 to 10 membered heterocyclyl;
• each R33 independently is selected from the group consisting of H, optionally substituted C1-12 alkyl, optionally substituted C2-12 alkenyl, optionally substituted C2-12 alkynyl, optionally substituted C3-12 cycloalkyl, optionally substituted C6-14 aryl, optionally substituted 3-14 membered heteroaryl, optionally substituted 3-12 membered heterocyclyl, optionally substituted 3-18 membered heteroarylalkyl, optionally substituted C6-18 arylalkyl, —CN, —C(O)R34, —CHO and —S(O)2R34;
• each R34 individually is optionally substituted C1-12 alkyl;
• wherein, each substituted Q3, substituted R30, substituted R31, substituted R32, substituted R33, or substituted R34 is independently substituted with one or more Q6;
• L is selected from the group consisting of —OC(O)N(R4)—, —N(R4)C(O)O—, —N(R4)S(O)2—, —N(R4)C(O)—, —C(O)—, —C(O)O—, —OC(O)—, —N(R4)N(R4)C(O)O—,
• and —N(R4)N(R4)—;
• Het is an optionally substituted 3-12 membered heterocyclyl or optionally substituted 3-14 membered heteroaryl;
• wherein, each substituted Het is substituted with one or more Q4;
• each Q4, independently, is selected from the group consisting of
• halogen, oxo, oxide, —NO2, —N(═O), —SR40, —S(O)R40, —S(O)2R40, —S(O)2NR40R41, —NR40C(O)R41, —NR40C(O)NR41R42, —NR40S(O)R41, —NR40S(O)2R41, —OP(O)R41R42, —P(O)R41R42, —P(O)OR41R42, —P(O)(OR41)OR42, —C(O)NR41R42, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted C3-6 cycloalkyl, optionally substituted C6-12 arylalkyl, optionally substituted C6-12 aryl, optionally substituted 3-14 membered heteroaryl, optionally substituted C1-6 alkyloxy, optionally substituted C2-6 alkenyloxy, optionally substituted C2-6 alkynyloxy, optionally substituted C3-6 cycloalkyloxy, optionally substituted C6-12 aryloxy, optionally substituted 3-14 membered heteroaryloxy, optionally substituted 4-12 membered heterocyclyloxy, optionally substituted —C(O)C1-6 alkyl, optionally substituted —C(O)C2-6 alkenyl, optionally substituted —C(O)C2-6 alkynyl, optionally substituted —C(O)C3-6 cycloalkyl, optionally substituted —C(O)C6-12 aryl, optionally substituted —C(O)-3-14 membered heteroaryl, optionally substituted —C(O)C6-12 arylalkyl, optionally substituted 3-10 membered heterocyclyl, —OH, —NR41R42, —C(O)OR40, —CN, —N3, —C(═NR43)NR41R42, —C(═NR43)OR40, —NR40C(═NR43)NR41R42, —NR41C(O)OR40, and —OC(O)NR41R42;
• each R40, R41, and R42, independently is selected from the group consisting of H, optionally substituted C1-12 alkyl, optionally substituted C2-12 alkenyl, optionally substituted C2-12 alkynyl, optionally substituted C3-12 cycloalkyl, optionally substituted
• C6-14 aryl, optionally substituted 3-14 membered heteroaryl, optionally substituted 3-12 membered heterocyclyl, optionally substituted 3-18 membered heteroarylalkyl, and optionally substituted C6-18 arylalkyl;
• or R41 and R42 taken together with the atoms to which they are attached form a 3 to 10 membered heterocyclyl;
• each R43, independently, is selected from the group consisting of H, optionally substituted C1-12 alkyl, optionally substituted C2-12 alkenyl, optionally substituted C2-12 alkynyl, optionally substituted C3-12 cycloalkyl, optionally substituted C6-14 aryl, optionally substituted 3-14 membered heteroaryl, optionally substituted 3-12 membered heterocyclyl, optionally substituted 3-18 membered heteroarylalkyl, optionally substituted C6-18 arylalkyl, —CN, —C(O)R44, —CHO and —S(O)2R44;
• each R44 individually is optionally substituted C1-12 alkyl;
• wherein, each substituted Q4, substituted R40, substituted R41, substituted R42, substituted R43, or substituted R44 is independently substituted with one or more Q5;
• each Q5, individually, is selected from the group consisting of
• halogen, oxo, oxide, —NO2, —N(═O), —SR50, —S(O)R50, —S(O)2R50, —S(O)2NR50R51, —NR50C(O)R51, —NR50C(O)NR51R52, —NR50S(O)R51, —NR50S(O)2R51, —OP(O)R51R52, —P(O)R51R52, —P(O)OR51R52, —P(O)(OR51)OR52, —C(O)NR51R52, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted C3-6 cycloalkyl, optionally substituted C6-12 arylalkyl, optionally substituted C6-12 aryl, optionally substituted 3-14 membered heteroaryl, optionally substituted C1-6 alkyloxy, optionally substituted C2-6 alkenyloxy, optionally substituted C2-6 alkynyloxy, optionally substituted C3-6 cycloalkyloxy, optionally substituted C6-12 aryloxy, optionally substituted 3-14 membered heteroaryloxy, optionally substituted 4-12 membered heterocyclyloxy, optionally substituted —C(O)C1-6 alkyl, optionally substituted —C(O)C2-6 alkenyl, optionally substituted —C(O)C2-6 alkynyl, optionally substituted —C(O)C3-6 cycloalkyl, optionally substituted —C(O)C6-12 aryl, optionally substituted —C(O)-3-14 membered heteroaryl, optionally substituted —C(O)C6-12 arylalkyl, optionally substituted 3-10 membered heterocyclyl, —OH, —NR51R52, —C(O)OR50, —CN, —N3, —C(═NR53)NR51R52, —C(═NR53)OR50, —NR50C(═NR53)NR51R52, —NR51C(O)OR50, and —OC(O)NR51R52;
• each R50, R51, and R52, independently is selected from the group consisting of H, optionally substituted C1-12 alkyl, optionally substituted C2-12 alkenyl, optionally substituted C2-12 alkynyl, optionally substituted C3-12 cycloalkyl, optionally substituted C6-14 aryl, optionally substituted 3-14 membered heteroaryl, optionally substituted 3-12 membered heterocyclyl, optionally substituted 3-18 membered heteroarylalkyl, and optionally substituted C6-18 arylalkyl;
• or R51 and R52 taken together with the atoms to which they are attached form a 3 to 10 membered heterocyclyl;
• each R53, independently, is selected from the group consisting of H, optionally substituted C1-12 alkyl, optionally substituted C2-12 alkenyl, optionally substituted C2-12 alkynyl, optionally substituted C3-12 cycloalkyl, optionally substituted C6-14 aryl, optionally substituted 3-14 membered heteroaryl, optionally substituted 3-12 membered heterocyclyl, optionally substituted 3-18 membered heteroarylalkyl, optionally substituted C6-18 arylalkyl, —CN, —C(O)R54, —CHO and —S(O)2R54;
• each R54, independently, is optionally substituted C1-12 alkyl;
• wherein, each substituted Q5, substituted R50, substituted R51, substituted R52, substituted R53, or substituted R54 is independently substituted with one or more Q6;
• each Q6, independently, is selected from the group consisting of halogen, oxo, oxide, —NO2, —N(═O), —SR60, —S(O)R60, —S(O)2R60, —S(O)2NR60R61, —NR60C(O)R61,
• —NR60C(O)NR61R62, —NR60S(O)R61, —NR60S(O)2R61, —OP(O)R61R62,
• —P(O)R61R62, —P(O)OR61R62, —P(O)(OR61)OR62, —C(O)NR61R62, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C6-12 arylalkyl, C6-12 aryl, 3-14 membered heteroaryl, C1-6 alkyloxy, C2-6 alkenyloxy, C2-6 alkynyloxy, C3-6 cycloalkyloxy, C6-12 aryloxy, 3-14 membered heteroaryloxy, 4-12 membered heterocyclyloxy, —C(O)C1-6 alkyl, —C(O)C2-6 alkenyl, —C(O)C2-6 alkynyl, —C(O)C3-6 cycloalkyl, —C(O)C1-6 haloalkyl, —C(O)C6-12 aryl, —C(O)-3-14 membered heteroaryl, —C(O)C6-12 arylalkyl, 3-10 membered heterocyclyl, —OH, —NR61R62, —C(O)OR60, —CN, —N3, —C(═NR63)NR61R62, —C(═NR63)OR60, —NR60C(═NR63)NR61R62, —NR61C(O)OR60, and —OC(O)NR61R62;
• each R60, R61, and R62, independently, is selected from the group consisting of H, C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, C3-12 cycloalkyl, C1-12 haloalkyl, C6-14 aryl, 3-14 membered heteroaryl, 3-12 membered heterocyclyl, 3-18 membered heteroarylalkyl, and C6-18 arylalkyl;
• or R61 and R62 taken together with the atoms to which they are attached form a 3 to 10 membered heterocyclyl;
• each R63 independently is selected from the group consisting of H, C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, C3-12 cycloalkyl, C6-14 aryl, 3-14 membered heteroaryl, 3-12 membered heterocyclyl, 3-18 membered heteroarylalkyl, C6-18 arylalkyl, —CN, —C(O)R64, —CHO and —S(O)2R64;
• each R64 individually is C1-12 alkyl;
• each R4 is independently H, C1-C12 alkyl, C3-C12 cycloalkyl, 3-14 membered heteroaryl or 3-12 membered heterocyclyl wherein each C1-C12 alkyl, C3-C12 cycloalkyl, 3-14 membered heteroaryl or 3-12 membered heterocyclyl is optionally substituted with one or more Q1;
• each R5 is independently C1-C12 alkyl, C3-C12 cycloalkyl, 3-14 membered heteroaryl or 3-12 membered heterocyclyl wherein each C1-C12 alkyl, C3-C12 cycloalkyl, 3-14 membered heteroaryl or 3-12 membered heterocyclyl is optionally substituted with one or more Q1;
• R6 is C1-C12 alkylyne, C3-C12 cycloalkylyne, or 3-12 membered heterocyclylyne wherein each C1-C12 alkylyne, C3-C12 cycloalkylyne, or 3-12 membered heterocyclylyne is optionally substituted with one or more Q1;
• and
• R7 is selected from the group consisting of optionally substituted C1-12 alkyl, optionally substituted C2-12 alkenyl, optionally substituted C2-12 alkynyl, optionally substituted C3-12 cycloalkyl, optionally substituted C6-14 aryl, optionally substituted 3-14 membered heteroaryl, optionally substituted 3-12 membered heterocyclyl, optionally substituted 3-18 membered heteroarylalkyl, optionally substituted 3-18 membered heterocyclylalkyl and optionally substituted C6-18 arylalkyl;
• wherein, each substituted R7 is substituted with one or more Q2.