4′-difluoromethyl substituted nucleoside derivatives as inhibitors of influenza RNA replication

A method for treating an Influenza infection comprising administering to a patient in need thereof a therapeutically effective amount of a compound of Formula I

• wherein:
• Y is H or P(═X)(R′)(R);
• R is O—R1 or NHR1′;
• R1′ is —C(R2a)(R2b)C(═)OR3;
• R′ is N(R4)C(R2a)(R2b)C(═O)OR3, —OP(═O)(OH)OP(═O)(OH)OH, or —OR3;
• R1 is H, lower haloalkyl, or aryl, wherein aryl is phenyl or naphthylenyl, optionally substituted with one or more lower alkyl, lower alkenyl, lower alkynyl, lower alkoxy, halo, lower haloalkyl, —N(R1a)2, acylamino, —SO2N(R1a)2, —C(═O)R1b, —SO2(R1c), —NHSO2(R1c), nitro, cyano, or R1″;
• each R1a is independently H or lower alkyl;
• each R1b is independently —OR1a or —N(R1a)2;
• each R1c is lower alkyl;
• each R2a and R2b is independently H, lower alkyl, —(CH2)rN(R1a)2, lower hydroxyalkyl, —CH2 SH, —(CH2)S(O)pMe, —(CH2)nNHC(═NH)NH2, (1H-indol-3 -yl)methyl, (1H-indol-4-yl)methyl, —(CH2)mC(═O)R1b, aryl and aryl lower alkyl, wherein aryl is optionally substituted with one or more hydroxy, lower alkyl, lower alkoxy, halo, nitro or cyano;
• m is 0, 1, or 2;
• n is 1, 2, or 3;
• p is 1 or 2;
• r is 1 or 2;
• or R2a is H and R2b and R4 together form (CH2)n;
• each R3 is independently H, lower alkyl, lower haloalkyl, phenyl or phenyl lower alkyl, wherein phenyl and phenyl lower alkyl are optionally substituted with lower alkoxy;
• or one R3 and R1″ together form CH2;
• each R4 is independently H, lower alkyl;
• or R2b and R4 together form (CH2)3;
• Rw, Ry, and Rz are each independently H, OH or F;
• Rx is H, OH, or F;
• or one R3 and Rx together form a bond;
• or R1 and Rx together form a bond;
• and
• X is O or S;
• or a pharmacologically acceptable salt thereof.