Substituted aminothiazolopyrimidinediones

Patent metadata

Field	Value
Publication number	US-10590146-B2
Application number	US-201715852108-A
Country	US
Kind code	B2
Filing date	Dec 22, 2017
Priority date	Jun 30, 2015
Publication date	Mar 17, 2020
Grant date	Mar 17, 2020

Abstract

The present invention relates to compounds of formula (I),

wherein R 1 to R 4 are as described herein, and their prodrugs or pharmaceutically acceptable salt, enantiomer or diastereomer thereof, and compositions including the compounds and methods of using the compounds.

First claim

The invention claimed is:

1. A compound of formula (I),

wherein:
R 1 is H, C 1-6 alkyl, C 3-7 cycloalkyl or phenylC 1-6 alkyl, said phenylC 1-6 alkyl being unsubstituted or substituted with one to three substituents independently selected from C 1-6 alkyl and halogen;
R 2 is H or C 1-6 alkyl;
R 3 is C 1-6 alkyl; and
R 4 is C 1-6 alkyl;
or pharmaceutically acceptable salt, enantiomer or diastereomer thereof.

2. A compound of formula (Ia),

wherein
R 1 is H, C 1-6 alkyl, C 3-7 cycloalkyl or phenylC 1-6 alkyl, said phenylC 1-6 alkyl being unsubstituted or substituted with one to three substituents independently selected from C 1-6 alkyl and halogen;
R 2 is H or C 1-6 alkyl;
R 3 is C 1-6 alkyl; and
R 4 is C 1-6 alkyl;
or pharmaceutically acceptable salt, enantiomer or diastereomer thereof.

3. A compound according to claim 1 , wherein:
R 1 is H, methyl, propyl, cyclopropyl, benzyl, fluorobenzyl, chlorobenzyl, fluorochlorobenzyl or methylbenzyl;
R 2 is H or methyl;
R 3 is methyl;
R 4 is ethyl;
or pharmaceutically acceptable salt, enantiomer or diastereomer thereof.

4. A compound according to of claim 1 , wherein R 1 is H, C 1-6 alkyl or phenylC 1-6 alkyl; or a pharmaceutically acceptable salt, enantiomer, or diastereomer thereof.

5. A compound according to claim 1 , wherein R 1 is H, methyl or benzyl; or pharmaceutically acceptable salt, enantiomer, or diastereomer thereof.

6. A compound according to claim 1 , wherein R 2 is H; or a pharmaceutically acceptable salt, enantiomer, or diastereomer thereof.

7. A compound selected from:
5-Amino-3-[(2R,3S,5S)-3-[(1S)-1-aminoethyl]-5-[(1S)-1-hydroxypropyl]tetrahydrofuran-2-yl]-6H-thiazolo[4,5-d]pyrimidine-2,7-dione;
5-amino-3-[(2R,3S,5S)-3-[(1R)-1-aminoethyl]-5-[(1S)-1-hydroxypropyl]tetrahydrofuran-2-yl]-6H-thiazolo[4,5-d]pyrimidine-2,7-dione;
5-Amino-3-[(2R,3S,5S)-5-[(1S)-1-hydroxypropyl]-3-[(1R)-1-(methylamino)ethyl]tetrahydrofuran-2-yl]-6H-thiazolo[4,5-d]pyrimidine-2,7-dione;
5-Amino-3-[(2R,3S,5S)-5-[(1S)-1-hydroxypropyl]-3-[(1R)-1-(propylamino)ethyl]tetrahydrofuran-2-yl]-6H-thiazolo[4,5-d]pyrimidine-2,7-dione;
5-Amino-3-[(2R,3S,5S)-3-[(1R)-1-(cyclopropylamino)ethyl]-5-[(1S)-1-hydroxypropyl]tetrahydrofuran-2-yl]-6H-thiazolo[4,5-d]pyrimidine-2,7-dione;
5-Amino-3-[(2R,3S,5S)-3-[(1R)-1-(benzylamino)ethyl]-5-[(1S)-1-hydroxypropyl]tetrahydrofuran-2-yl]-6H-thiazolo[4,5-d]pyrimidine-2,7-dione;
5-Amino-3-[(2R,3S,5S)-5-[(1S)-1-hydroxypropyl]-3-[(1S)-1-(methylamino)ethyl]tetrahydrofuran-2-yl]-6H-thiazolo[4,5-d]pyrimidine-2,7-dione;
5-Amino-3-[(2R,3S,5S)-3-[(1S)-1-(benzylamino)ethyl]-5-[(1S)-1-hydroxypropyl]tetrahydrofuran-2-yl]-6H-thiazolo[4,5-d]pyrimidine-2,7-dione; and
5-Amino-3-[(2R,3S,5S)-3-[(1R)-1-(dimethylamino)ethyl]-5-[(1S)-1-hydroxypropyl]tetrahydrofuran-2-yl]-6H-thiazolo[4,5-d]pyrimidine-2,7-dione;
or pharmaceutically acceptable salt, enantiomer or diastereomer thereof.

8. A pharmaceutically composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt, enantiomer, or diastereomer thereof, and a therapeutically inert carrier.

9. A compound according to claim 2 , wherein:
R 1 is H, methyl, propyl, cyclopropyl, benzyl, fluorobenzyl, chlorobenzyl, fluorochlorobenzyl or methylbenzyl;
R 2 is H or methyl;
R 3 is methyl; and
R 4 is ethyl;
or a pharmaceutically acceptable salt, enantiomer, or diastereomer thereof.

10. A compound according to claim 2 , wherein R 1 is H, C 1-6 alkyl or phenylC 1-6 alkyl; or a pharmaceutically acceptable salt, enantiomer, or diastereomer thereof.

11. A compound according to claim 2 , wherein R 1 is H, methyl or benzyl; or a pharmaceutically acceptable salt, enantiomer, or diastereomer thereof.

12. A compound according to claim 2 , wherein R 2 is H; or a pharmaceutically acceptable salt, enantiomer, or diastereomer thereof.

13. A pharmaceutical composition comprising a compound according to claim 2 , or a pharmaceutically acceptable salt, enantiomer, or diastereomer thereof, and a therapeutically inert carrier.

14. A pharmaceutical composition comprising a compound according to claim 7 , or a pharmaceutically acceptable salt, enantiomer, or diastereomer thereof, and a therapeutically inert carrier.

Assignees

• Hoffmann La Roche

Inventors

• Wang Lisha
• Yun Hongying
• Zheng Xiufang

Classifications

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title

• C07D513/04 Primary

  Ortho-condensed systems · CPC title

• A61P31/20

  for DNA viruses · CPC title

• C07H1/00

  Processes for the preparation of sugar derivatives · CPC title

• C07H19/24

  Heterocyclic radicals containing oxygen or sulfur as ring hetero atom · CPC title