Substituted nucleosides, nucleotides and analogs thereof

Patent metadata

Field	Value
Publication number	US-2016016987-A1
Application number	US-201514836784-A
Country	US
Kind code	A1
Filing date	Aug 26, 2015
Priority date	Dec 21, 2012
Publication date	Jan 21, 2016
Grant date	—

Abstract

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.

First claim

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.

Assignees

• Alios Biopharma Inc

Inventors

• Beigelman Leonid
• Wang Guangyi
• Smith David Bernard

Classifications

• C07H19/207 Primary

  the phosphoric or polyphosphoric acids being esterified by a further hydroxylic compound, e.g. flavine adenine dinucleotide or nicotinamide-adenine dinucleotide · CPC title

• A61P31/14

  for RNA viruses · CPC title

• C07H19/16

  Purine radicals · CPC title

• C07H19/06

  Pyrimidine radicals · CPC title

• C07H19/10 Primary

  with the saccharide radical esterified by phosphoric or polyphosphoric acids · CPC title