| 摘要 |
Disclosed is a set of 36 specific compounds which are uracil and cytosine nitrile containing pyrimidine N-nucleoside analogues / cyano sofosbuvir analogs for treating viruses of the flaviviridae family including the treatment of hepatitis C virus (HCV), wherein for the general formula I, Base is selected from uracil and cytosine; R1 is H or alkyl; R2 is H or ORa; or R1 and R2 taken together with the carbon to which they are attached form a 3- to 6-membered cycloalkyl ring wherein 1 to 3 carbon atoms of said cycloalkyl ring is optionally replaced by oxygen; R3, R4, and R5 are each independently H, ORa, or azido; R6 is cyano; each Ra is independently H, alkyl, or acyl; R7 is a phosphate or phosphoramidate analogue or derivative; R8 is H or alkyl; and wherein the remaining substituents are as defined herein. Also disclosed is a pharmaceutical composition comprising a therapeutically effective amount of a compound as defined above and a pharmaceutically acceptable carrier, and optionally further comprising at least one additional therapeutic agent selected from the group consisting of interferons, ribavirin analogs, NS3 protease inhibitors, NS5a inhibitors, NS5b polymerase inhibitors, alpha-glucosidase 1 inhibitors, cyclophilin inhibitors, hepatoprotectants, other nucleoside inhibitors of HCV, non-nucleoside inhibitors of HCV, and other drugs for treating HCV. Some of the 36 specific compounds include isopropyl (2S)-2-[[[(2R,3R,4R,5S)-5-cyano-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxy-4-methyl-tetrahydrofuran-2-yl]methoxy-phenoxy-phosphoryl]amino]propanoate, (2S)-2-[[[(2R,3R,4R,5S)-5-cyano-5-(2-oxo-4-amino-pyrimidin-1-yl)-3,4-dihydroxy-4-methyl-tetrahydrofuran-2-yl]methoxy-phenoxy-phosphoryl]amino]propanoate and (2S)-2-[[[(1R)-1-[(2R,3R,4R,5S)-5-cyano-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxy-4-methyl-tetrahydrofuran-2-yl]ethoxy]-phenoxy-phosphoryl]amino]propanoate. |
