Antiviral acyclonucleoside analogues for use in treating a viral infection

Patent metadata

Field	Value
Publication number	US-11603380-B2
Application number	US-201917050263-A
Country	US
Kind code	B2
Filing date	Apr 23, 2019
Priority date	Apr 23, 2018
Publication date	Mar 14, 2023
Grant date	Mar 14, 2023

Abstract

The present invention concerns a compound having the following formula (I):as well as its use as a medicament, especially for its use for treating viral infections.

First claim

The invention claimed is:

1. A compound having the following formula (I′):

wherein:
n is 0, 1 or 2;
X 1 , X 2 , and X 3 are, independently from each other, CH or N;
R″ is selected from the group consisting of: H, NH 2 , and halogen atoms;
R is selected from the group consisting of:
—NR a R b groups, R a and R b being independently from each other H, a (C 1 -C 6 )alkyl group or a (C 3 -C 6 )cycloalkyl group;
halogen atoms; and
(C 1 -C 6 )alkoxy groups;

R′ is a group of formula (1)

wherein R 1 and R 2 are independently from each other selected from the group consisting of:
OH;
(C 1 -C 6 )alkoxy groups;
—O-A 1 -O-A 2 groups; wherein A 1 is an alkylene radical comprising from 1 to 6 carbon atoms, and A 2 is a (C 1 -C 20 )alkyl group;
—O-A 3 -O—C(═O)-A 4 , wherein A 3 is an alkylene radical comprising from 1 to 6 carbon atoms, and A 4 is a (C 1 -C 6 )alkyl group; and
—O-A 5 -O—C(═O)—O—A 6 , wherein A 5 is an alkylene radical comprising from 1 to 6 carbon atoms, and A 6 is a (C 1 -C 6 )alkyl group;
or R′ is a group of formula (2):

wherein:
R 4 is a (C 6 -C 10 )aryl group;
R 5 is a (C 1 -C 6 )alkyl group,
R 6 is selected from the group consisting of: (C 1 -C 6 )alkyl groups, and (C 6 -C 10 )aryl groups,
R 3 is selected from the group consisting of:
H;
(C 1 -C 6 )alkyl groups;
-A 7 -OH, wherein A 7 is an alkylene radical comprising from 1 to 6 carbon atoms; and
-A 8 -O—C(═O)-A 9 , wherein A 8 is an alkylene radical comprising from 1 to 6 carbon atoms, and A 9 is a (C 1 -C 6 )alkyl group;
or a pharmaceutically acceptable salt, racemate, diastereoisomer or enantiomer thereof.

2. The compound of claim 1 , having one of the following formulae (II) or (II′):

or a pharmaceutically acceptable salt, racemate, diastereoisomer or enantiomer thereof.

3. The compound of claim 1 , having one of the following formulae (III) or (III′):

or a pharmaceutically acceptable salt, racemate, diastereoisomer or enantiomer thereof.

4. The compound of claim 1 , having the following formula (IV):

or a pharmaceutically acceptable salt, racemate, diastereoisomer or enantiomer thereof.

5. A medicament comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof.

6. The compound of claim 1 , wherein R 1 and R 2 , identical or different, are selected from the group consisting of:
—O-A 1 -O-A 2 ,
—O-A 3 -O—C(═O)-A 4 , and
—O-A 5 -O—C(═O)—O—A 6 groups.

7. The compound of claim 1 , wherein R 1 and R 2 , identical or different, are selected from the group consisting of:
—O—(CH 2 ) 3 —O—(CH 2 ) 15 —CH 3 ,
—O—CH 2 —O—C(═O)-tBu, and
—O—CH 2 —O—C(═O)—O—iPr.

8. The compound of claim 1 , wherein R is NH 2 .

9. The compound of claim 1 , wherein R 3 is H or —CH 2 OCOCH 3 .

10. The compound of claim 4 , wherein R 3 is H or —CH 2 OCOCH 3 .

11. The compound of claim 4 , wherein R 4 is a phenyl or naphthyl group.

12. A method for treating a viral infection, comprising administering a pharmaceutically acceptable amount of at least one compound of claim 1 to a patient in need thereof.

13. The method of claim 12 , wherein the viral infection is an infection due to a DNA virus or an RNA virus.

14. The method of claim 12 , wherein the viral infection is an infection due to a virus selected from the group consisting of Hepatitis B virus, Varicella-zoster virus, Cytomegalovirus, Adenovirus, Herpes virus, Poxvirus, Feline corona virus, Filovirus, Papovarirus, Parvovirus, Myxoma virus, and Hepadnavirus.

Assignees

• Centre Nat Rech Scient
• Univ Orleans
• Neovirtech

Inventors

• Agrofoglio Luigi
• Roy Vincent
• De Schutter Coralie
• Bessieres Maxime
• Gallardo Franck

Classifications

• C07F9/6515

  having three nitrogen atoms as the only ring hetero atoms · CPC title

• A61P31/12

  Antivirals · CPC title

• C07F9/6512

  having the nitrogen atoms in positions 1 and 3 · CPC title

• C07F9/6521 Primary

  Six-membered rings · CPC title

• A61P31/20

  for DNA viruses · CPC title