Methods For Treating Arenaviridae And Coronaviridae Virus Infections
Provided are methods for treating Arenaviridae and Coronaviridae virus infections by administering nucleosides and prodrugs thereof, of Formula I:
wherein the 1′ position of the nucleoside sugar is substituted. The compounds, compositions, and methods provided are particularly useful for the treatment of Lassa virus and Junin virus infections.
Claim CLM-00001. 1. A method for treating a Coronaviridae infection in a human in need thereof, comprising administering a therapeutically effective amount of a compound of Formula IV: or a pharmaceutically acceptable salt thereof; R7 is selected from the group consisting of
a) —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), and —SO2NR11R12,
whereineach R11 and 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 is optionally replaced with —O—, —S— or —NRa—;each Ra is independently H, (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl, aryl(C1-C8)alkyl, (C4-C8)carbocyclylalkyl, —C(═O)R, —C(═O)OR, —C(═O)NR2, —C(═O)SR, —S(O)R, —S(O)2R, —S(O)(OR), —S(O)2(OR), or —SO2NR2;wherein 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; andwherein each (C1-C8)alkyl, (C2-C8)alkenyl, (C2-C8)alkynyl or aryl(C1-C8)alkyl of each R11 and 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 is optionally replaced with —O—, —S— or —NRa—,wherein:
Rc is selected from the group consisting of phenyl, 1-naphthyl, 2-naphthyl,Rd is H or CH3;Re1 and Re2 are each independently H, C1-C6 alkyl or benzyl; andRf is selected from the group consisting of H, C1-C8 alkyl, benzyl, C3-C6 cycloalkyl, and —CH2—C3-C6 cycloalkyl;andd) a group of the formula:whereinQ is O, S, NR, +N(O)(R), N(OR), +N(O)(OR), or N—NR2;Z1 and Z2, when taken together, are -Q1(C(Ry)2)3Q1-;wherein
each Q1 is independently O, S, or NR; andeach Ry is independently H, F, Cl, Br, I, OH, R, —C(=Q2)R, —C(=Q2)OR, —C(=Q2)N(R)2, —N(R)2, —+N(R)3, —SR, —S(O)R, —S(O)2R, —S(O)(OR), —S(O)2(OR), —OC(=Q2)R, —OC(=Q2)OR, —OC(=Q2)(N(R)2), —SC(=Q2)OR, —SC(=Q2)(N(R)2), —N(R)C(=Q2)R, —N(R)C(=Q2)OR, —N(R)C(=Q2)N(R)2, —SO2NR2, —CN, —N3, —NO2, —OR, or Z3; or when taken together, two Ry on the same carbon atom form a carbocyclic ring of 3 to 7 carbon atoms;each Q2 is independently, O, S, NR, +N(O)(R), N(OR), +N(O)(OR), or N—NR2; orZ1 and Z2 are each, independently, a group of the Formula Ia:wherein:
each Q3 is independently a bond, O, CR2, NR, +N(O)(R), N(OR), +N(O)(OR), N—NR2, S—S, S(O), or S(O)2;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; Z3 is Z4 or Z5; Z4 is R, —C(Q2)Ry, —C(Q2)Z5, —SO2Ry, or —SO2Z5; and Z5 is a carbocycle or a heterocycle wherein Z5 is independently substituted with 0 to 3 Ry groups.
