Acyclic antivirals

Patent metadata

Field	Value
Publication number	US-11472826-B2
Application number	US-202016916618-A
Country	US
Kind code	B2
Filing date	Jun 30, 2020
Priority date	Mar 9, 2016
Publication date	Oct 18, 2022
Grant date	Oct 18, 2022

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 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

and an optionally substituted

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 or ten-membered ring system;
R 3a is hydroxy(C 1-4 alkyl)-;
R 3b is 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);
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≡CN, 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 selected from the group consisting of: an unsubstituted

an unsubstituted

an unsubstituted

an unsubstituted

an unsubstituted

an unsubstituted

an unsubstituted

an unsubstituted

an unsubstituted

an unsubstituted

and an unsubstituted

3. The compound of claim 1 , wherein R 1 and R 2 are each independently selected from the group consisting of O − , —OH, an optionally substituted —O-aryl, an optionally substituted —O-heteroaryl, an optionally substituted N-linked amino acid and an optionally substituted N-linked amino acid ester derivative.

4. The compound of claim 1 , wherein R 3b is hydrogen an unsubstituted C 1-4 alkyl, halogen(C 1-4 alkyl), hydroxy(C 1-4 alkyl), alkoxy(C 1-4 alkyl), acyl(C 1-4 alkyl) or cyano(C 1-4 alkyl).

5. The compound of claim 1 , wherein and R 3b is hydrogen.

6. The compound of claim 1 , wherein R 3b is selected from the group consisting of hydrogen, fluoro, CH 3 , CH 2 F, CHF 2 , CH 2 OH and —CH 2 —O—CH 3 .

7. The compound of claim 1 , wherein R 3a is CH 3 OH.

8. The compound of claim 1 , wherein n is 1.

9. The compound of claim 1 , wherein m is 1.

10. The compound of claim 1 selected from the group consisting of:

or a pharmaceutically acceptable salt of any of the foregoing.

11. The compound of

Assignees

• Janssen Pharmaceutica Nv

Inventors

• Beigelman Leonid
• Wang Guangyi
• Zhong Minghong

Classifications

• 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

• A61P31/18

  for HIV · CPC title

• A61F13/512

  characterised by its apertures, e.g. perforations · CPC title

• A61F13/51113

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

• A61F13/51405

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