SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF
Disclosed herein are nucleotide analogs, methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a HCV infection with one or more nucleotide analogs.
1 . (canceled)
2 . A compound of Formula (I), or a pharmaceutically acceptable salt thereof, having the structure:
wherein:
B 1 is
R 1 is methyl or ethynyl;
R 2 is hydroxyl or fluoro;
R 3 is hydroxyl;
R 4 is hydrogen or
R 5A is O − , OH, or an optionally substituted N-linked α-amino acid ester derivative;
R 5B is O − , OH, an —O-optionally substituted aryl, or
where n is 0 or 1;
R 6B is H;
R 6C is H or unsubstituted C 1-6 alkyl;
R 9 , R 10 and R 11 are independently absent or hydrogen; and
Z 1 is O or S.
3 . The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein Z 1 is S.
4 . The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein B 1 is
5 . The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein R 6C is H or methyl.
6 . The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein R 1 is methyl.
7 . The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein R 1 is ethynyl.
8 . The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein R 2 is hydroxyl.
9 . The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein R 2 is fluoro.
10 . The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein R 5A is an optionally substituted N-linked a-amino acid ester derivative; and R 5B is an —O-optionally substituted aryl.
11 . The compound of claim 10 , or a pharmaceutically acceptable salt thereof, wherein the optionally substituted N-linked α-amino acid ester derivative is N-alaninyl isopropyl ester, N-alaninyl cyclohexyl ester, N-alaninyl neopentyl ester, N-valinyl isopropyl ester or N-leucinyl isopropyl ester.
12 . The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein R 5A is O − or OH; and R 5B is O − , OH or
13 . The compound of claim 12 , or a pharmaceutically acceptable salt thereof, wherein n is 1.
14 . The compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein Z 1 is O.
15 . The compound of claim 14 , or a pharmaceutically acceptable salt thereof, wherein B 1 is
16 . The compound of claim 15 , or a pharmaceutically acceptable salt thereof, wherein R 1 is methyl.
17 . The compound of claim 15 , or a pharmaceutically acceptable salt thereof, wherein R 1 is ethynyl.
18 . The compound of claim 15 , or a pharmaceutically acceptable salt thereof, wherein R 2 is hydroxyl.
19 . The compound of claim 15 , or a pharmaceutically acceptable salt thereof, wherein R 2 is fluoro.
20 . The compound of claim 15 , or a pharmaceutically acceptable salt thereof, wherein R 1 is methyl and R 2 is fluoro.
21 . The compound of claim 15 , or a pharmaceutically acceptable salt thereof, wherein R 5A is an optionally substituted N-linked a-amino acid ester derivative; and R 5B is an —O-optionally substituted aryl.
22 . The compound of claim 21 , or a pharmaceutically acceptable salt thereof, wherein the optionally substituted N-linked α-amino acid ester derivative is N-alaninyl isopropyl ester, N-alaninyl cyclohexyl ester, N-alaninyl neopentyl ester, N-valinyl isopropyl ester or N-leucinyl isopropyl ester.
23 . The compound of claim 15 , or a pharmaceutically acceptable salt thereof, wherein R 5A is O − or OH; and R 5B is O − , OH or
24 . The compound of claim 23 , or a pharmaceutically acceptable salt thereof, wherein n is 1.