2'-fluoro substituted carba-nucleoside analogs for antiviral treatment

A compound of Formula I:

• or a pharmaceutically acceptable salt, thereof;
• wherein:
• R1 is (C1-C8)alkyl, (C4-C8)carbocyclylalkyl, (C1-C8)substituted alkyl, (C2-C8)alkenyl, (C2-C8)substituted alkenyl, (C2-C8)alkynyl, (C2-C8)substituted alkynyl, or aryl(C1-C8)alkyl;
• R2 is halogen;
• each R3, R4, or R5 is independently H, ORa, N(Ra)2, N3, CN, NO2, S(O)nRa, halogen, (C1-C8)alkyl, (C4-C8)carbocyclylalkyl, (C1-C8)substituted alkyl, (C2-C8)alkenyl, (C2-C8)substituted alkenyl, (C2-C8)alkynyl, (C2-C8)substituted alkynyl, or aryl(C1-C8)alkyl;
• or any two of R3, R4 or R5 on adjacent carbon atoms when taken together are —O(CO)O— or when taken together with the ring carbon atoms to which they are attached form a double bond;
• R6 is H, ORa, N(Ra)2, N3, CN, NO2, S(O)nRa, —C(═O)OR11, —C(═O)NR11R12, —S(O)R11, —S(O)2R11, —S(O)(OR11), —S(O)2(OR11), —SO—NR11R12, halogen, (C1-C8)alkyl, (C4-C8)carbocyclylalkyl, (C1-C8)substituted alkyl, (C2-C8)alkenyl, (C2-C8)substituted alkenyl, (C2-C8)alkynyl, (C2-C8)substituted alkynyl, or aryl(C1-C8)alkyl;
• each n is independently 0, 1, or 2;
• each Ra is independently H, (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, aryl(C1-C8)alkyl, (C4-C8)carbocyclylalkyl, —C(═O)R11, —C(═O)OR11, —C(═O)NR11R12, —C(═O)SR11, —S(O)R11, —S(O)2R11, —S(O)(OR11), —S(O)2(OR11), or —SO2NR11R12;
• R7 is H, —C(═O)R11, —C(═O)OR11, —C(═O)NR11R12, —C(═O)SR11, —S(O)R11, —S(O)2R11, —S(O)(OR11), —S(O)2(OR11), —SO2NR11R12, or
• each Y or Y1 is, independently, O, S, NR, +N(O)(R), N(OR), +N(O)(OR), or N—NR2;
• W1 and W2, when taken together, are —Y3(C(Ry)2)3Y3—;
• or one of W1 or W2 together with either R3 or R4 is —Y3— and the other of W1 or W2 is Formula Ia;
• or W1 and W2 are each, independently, a group of the Formula Ia:
• wherein:
• each Y2 is independently a bond, O, CR2, NR, +N(O)(R), N(OR), +N(O)(OR), N—NR2, S, S—S, S(O), or S(O)2;
• each Y3 is independently O, S, or NR;
• M2 is 0, 1 or 2;
• each Rx is independently Ry or the formula:
• wherein:
• each M1a, M1c, and M1d is independently 0 or 1;
• M12c is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12;
• each Ry is independently H, F, Cl, Br, I, OH, R, —C(═Y1)R, —C(═Y1)OR, —C(═Y1)N(R)2, —N(R)2, —+N(R)3, —SR, —S(O)R, —S(O)2R, —S(O)(OR), —S(O)2(OR), —OC(═Y1)R, —OC(═Y1)OR, —OC(═Y1)(N(R)2), —SC(—Y1)R, —SC(═Y1)OR, —SC(═Y1)(N(R)2), —N(R)C(═Y1)R, —N(R)C(═Y1)OR, —N(R)C(═Y1)N(R)2, —SO2NR2, —CN, —N3, —NO2, —OR, or W3;
• or when taken together, two Ry on the same carbon atom form a carbocyclic ring of 3 to 7 carbon atoms;
• each R is independently H, (C1-C8) alkyl, (C1-C8) substituted alkyl, (C2-C8)alkenyl, (C2-C8) substituted alkenyl, (C2-C8) alkynyl, (C2-C8) substituted alkynyl, C6-C20 aryl, C6-C20 substituted aryl, C2-C20 heterocyclyl, C2-C20 substituted heterocyclyl, arylalkyl or substituted arylalkyl;
• W3 is W4 or W5;
• W4 is R, —C(Y1)Ry, —C(Y1)W5, —SO2Ry, or —SO2W5;
• and W5 is a carbocycle or a heterocycle wherein W5 is independently substituted with 0 to 3 Ry groups;
• each X1 or X2 is independently C—R10 or N;
• each R8 is halogen, NR11R12, N(R11)OR11, NR11NR11R12, N3, NO, NO2, CHO, CN, —CH(═NR11), —CH═NNHR11, —CH═N(OR11), —CH(OR11)2, —C(═O)NR11R12, —C(═S)NR11R12, —C(═O)OR11, (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C4-C8)carbocyclylalkyl, optionally substituted aryl, optionally substituted heteroaryl, —C(═O)(C1-C8)alkyl, —S(O)n(C1-C8)alkyl, aryl(C1-C8)alkyl, OR11 or SR11;
• each R9 or R10 is independently H, halogen, NR11R12, N(R11)OR11, NR11NR11R12, N3, NO, NO2, CHO, CN, —CH(═NR11), —CH═NHNR11, —CH═N(OR11), —CH(OR11)2, —C(═O)NR11R12, —C(═S)NR11R12, —C(═O)OR11, R11, OR11 or SR11;
• each R11 or R12 is independently H, (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, (C4-C8)carbocyclylalkyl, optionally substituted aryl, optionally substituted heteroaryl, —C(═O)(C1-C8)alkyl, —S(O)n(C1-C8)alkyl or aryl(C1-C8)alkyl;
• or R11 and R12 taken together with a nitrogen to which they are both attached form a 3 to 7 membered heterocyclic ring wherein any one carbon atom of said heterocyclic ring can optionally be replaced with —O—, —S— or —NRa—;
• wherein each (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl or aryl(C1-C8)alkyl of each R1, R3, R4, R5, R6, R11 or R12 is, independently, optionally substituted with one or more halo, hydroxy, CN, N3, N(Ra)2 or ORa;
• and wherein one or more of the non-terminal carbon atoms of each said (C1-C8)alkyl may be optionally replaced with —O—, —S— or —NRa.