2′, 4′-difluoro-2′-methyl substituted nucleoside derivatives as inhibitors of HCV RNA replication

摘要

The present disclosure relates to compounds of Formula (I): Also disclosed are pharmaceutical compositions comprising compounds of Formula (I), methods of using the compounds of Formula (I) and/or compositions comprising the compounds of Formula (I) for the treatment of HCV.;

主权项

1. A compound of formula I wherein: R1 is H, lower haloalkyl, or aryl, wherein aryl is phenyl or naphthyl, optionally substituted with one or more lower alkyl, lower alkenyl, lower alkynyl, lower alkoxy, halo, lower haloalkyl, —N(R1a)2, acylamino, —SO2N(R1a)2, —COR1b, —SO2(R1c), —NHSO2(R1c), nitro or cyano; each R1a is independently H or lower alkyl; each R1b is independently —OR1a or —N(R1a)2; each R1c is lower alkyl; R2a and R2b are (i) independently H, lower alkyl, —(CH2)rN(R1a)2, lower hydroxyalkyl, —CH2SH, —(CH2)S(O)pMe, —(CH2)3NHC(═NH)NH2, (1H-indol-3-yl)methyl, (1H-indol-4-yl)methyl, —(CH2)mC(═O)R1b, aryl and aryl lower alkyl, wherein aryl may optionally be substituted with one or more hydroxy, lower alkyl, lower alkoxy, halo, nitro or cyano; (ii) R2a is H and R2b and R4 together form (CH2)3; (iii) R2a and R2b together form (CH2)n; or, (iv) R2a and R2b both are lower alkyl; R3 is H, lower alkyl, lower haloalkyl, phenyl or phenyl lower alkyl; R4 is H, lower alkyl, or R2b and R4 together form (CH2)3; R5 is H, C(═O)R1c, C(═O)R1b, P(═O)(OR1)(OR1a), or P(═O)(OR1)(NR4R7); R6 is H, methyl, or halo; R7 is C(R2aR2b)COOR3 m is 0 to 3; n is 4 or 5; p is 0 to 2; and r is 1 to 6; or a pharmacologically acceptable salt thereof.