Acyclic antivirals

Patent metadata

Field	Value
Publication number	US-2019055273-A1
Application number	US-201716090715-A
Country	US
Kind code	A1
Filing date	Mar 9, 2017
Priority date	Mar 9, 2016
Publication date	Feb 21, 2019
Grant date	—

Abstract

Disclosed herein are nucleotide analogs, methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a HBV and/or HDV and/or HIV infection with one or more nucleotide analogs

First claim

What is claimed is:

1 . A compound of Formula (I), or a pharmaceutically acceptable salt thereof, having the structure:

wherein:
B 1 is an optionally substituted C-linked bicyclic heteroaryl containing 9 atoms in the rings and 3, 4 or 5 nitrogens or an optionally substituted C-linked bicyclic heterocyclyl containing 9 atoms in the rings and 3, 4 or 5 nitrogens;
R 1 and R 2 are each independently selected from the group consisting of O − , —OH, an optionally substituted —O—C 1-24 alkyl, an optionally substituted —O—C 2-24 alkenyl, an optionally substituted —O—C 2-24 alkynyl, an optionally substituted —O—C 3-6 cycloalkyl, an optionally substituted —O—C 3-6 cycloalkenyl, an optionally substituted —O-aryl, an optionally substituted —O-heteroaryl, an optionally substituted —O-aryl(C 1-6 alkyl), an optionally substituted *—O—(CR 4 R 5 ) p —O—C 1-24 alkyl, an optionally substituted *—O—(CR 6 R 7 ) q —O—C 1-24 alkenyl,

an optionally substituted N-linked amino acid and an optionally substituted N-linked amino acid ester derivative; or
R 1 is

and R 2 is O − or OH; or
R 1 and R 2 are taken together to form a moiety selected from the group consisting of an optionally substituted

and an optionally substituted

wherein the phosphorus and the moiety form a six-membered to ten-membered ring system;
R 3a and R 3b are each independently selected from the group consisting of hydrogen, halogen, an unsubstituted C 1-4 alkyl, an unsubstituted C 3-6 cycloalkyl, cyano, halogen(C 1-4 alkyl), hydroxy(C 1-4 alkyl), alkoxy(C 1-4 alkyl), acyl(C 1-4 alkyl) and cyano(C 1-4 alkyl); or
R 3a and R 3b are taken together with the carbon to which they are connected to form an optionally substituted C 3-6 cycloalkyl;
each R 4 , each R 5 , each R 6 and each R 7 are independently hydrogen, an optionally substituted C 1-24 alkyl or alkoxy;
R 8 , R 9 , R 11 and R 12 are each independently selected from the group consisting of hydrogen, an optionally substituted C 1-24 alkyl and an optionally substituted aryl;
R 10 and R 13 are each independently selected from the group consisting of hydrogen, an optionally substituted C 1-24 alkyl, an optionally substituted aryl, an optionally substituted —O—C 1-24 alkyl, an optionally substituted —O-aryl, an optionally substituted —O-heteroaryl and an optionally substituted —O-monocyclic heterocyclyl;
R 14 is selected from the group consisting of hydrogen, an optionally substituted C 1-24 alkyl and an optionally substituted aryl;
R 15 and R 16 are each independently selected from the group consisting of —C≡N, an optionally substituted C 2-8 organylcarbonyl, an optionally substituted C 2-8 alkoxycarbonyl and an optionally substituted C 2-8 organylaminocarbonyl;
R 17 is selected from the group consisting of hydrogen, an optionally substituted C 1-24 -alkyl, an optionally substituted C 2-24 alkenyl, an optionally substituted C 2-24 alkynyl, an optionally substituted C 3-6 cycloalkyl and an optionally substituted C 3-6 cycloalkenyl;
R 19 , R 20 and R 21 are each independently absent or hydrogen;
m is 0 or 1;
n is 1 or 2;
p and q are each independently selected from the group consisting of 1, 2 and 3;
r is 1 or 2;
s is 0 or 1;
Z 1 is oxygen (O) or sulfur (S).

2 . The compound of claim 1 , wherein B 1 is an optionally substituted C-linked bicyclic heteroaryl containing 9 atoms in the rings and 3 nitrogens.

3 . The compound of claim 1 , wherein B 1 is an optionally substituted C-linked bicyclic heteroaryl containing 9 atoms in the rings and 4 nitrogens.

4 . The compound of claim 1 , wherein B 1 is an optionally substituted C-linked bicyclic heteroaryl containing 9 atoms in the rings and 5 nitrogens.

5 . The compound of claim 1 , wherein B 1 is an optionally substituted C-linked bicyclic heterocyclyl containing 9 atoms in the rings and 3 nitrogens.

6 . The compound of claim 1 , wherein B 1 is an optionally substituted C-linked bicyclic heterocyclyl containing 9 atoms in the rings and 4 nitrogens.

7 . The compound of claim 1 , wherein B 1 is an optionally substituted C-linked bicyclic heterocyclyl containing 9 atoms in the rings and 5 nitrogens.

8 . The compound of claim 1 , wherein B 1 has the structure

wherein X 1 , X 2 , X 3 , X 4 , X 5 , X 6 and X 7 are each independently selected from the group consisting of N and CR 25 , and each R 25 is independently selected from the group consisting of hydrogen, halogen, —NH 2 , —OH, an optionally substituted C 1-6 -alkyl and an optionally substituted (C 1-6 )alkoxy.

9 . The compound of claim 1 , wherein B 1 has the structure

wherein X 8 , X 9 , X 10 , X 11 , X 12 , X 13 and X 14 are each independently selected from the group consisting of N and CR 25 , and each R 25 is independently selected from the group consisting of hydrogen, halogen, —NH 2 , —OH, an optionally substituted C 1-6 -alkyl and an optionally substituted (C 1-6 )alkoxy.

10 . The compound of claim 1 , wherein B 1 has the structure

wherein X 15 and X 16 are each independently selected from the group consisting of N and CR 25 , and each R 25 is independently selected from the group consisting of hydrogen, halogen, —NH 2 , —OH, an optionally substituted C 1-6 -alkyl and an optionally substituted (C 1-6 )alkoxy.

11 . The compound of any one of claims 1 - 10 , wherein B 1 is selected from the group consisting of: an optionally substituted

an optionally substituted

an optionally substituted

an optionally substituted

an optionally substituted

an optionally substituted

an optionally substituted

an optionally substituted

an optionally substituted

an optionally substituted

an optionally substituted

Assignees

• Alios Biopharma Inc

Inventors

• Beigelman Leonid
• Wang Guangyi
• Zhong Minghong

Classifications

• A61F13/51405

  treated or coated, e.g. with moisture repellent agent · CPC title

• C07F9/6561 Primary

  containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings · CPC title

• A61F13/513

  {characterised by its function or properties, e.g. stretchability, breathability, rewet, visual effect;} having areas of different permeability · CPC title

• A61P31/20

  for DNA viruses · CPC title

• A61F13/51113

  comprising an additive, e.g. lotion or odour control (A61F13/51108 takes precedence) · CPC title