Novel 3-substituted 5-amino-6h-thiazolo[4,5-d]pyrimidine-2, 7-dione compounds for the treatment and prophylaxis of virus infection
AssigneeHoffmann-La Roche Inc.
InventorsDongdong Chen, Song Feng, Lu Gao, Chao Li, Baoxia Wang, Lisha Wang, Hongying Yun, Xiufang Zheng
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Abstract
The present invention relates to compounds of formula (I), wherein R1, R2 and R3 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.
Claims23
-36. (canceled)
A substantially diastereomerically pure compound of formula (Ia),
- wherein
- R1 is hydroxy or C1-6alkylcarbonyl-O—;
- R2 is C1-6 alkyl;
- and
- R3 is hydrogen or C1-6alkylcarbonyl;
- or a pharmaceutically acceptable salt thereof.
The substantially diastereomerically pure compound according to claim 36, wherein
- R1 is hydroxy or acetyloxy;
- R2 is ethyl or propyl;
- and
- R3 is hydrogen, acetyl or isobutyryl;
- or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof.
A compound that is 5-amino-3-[(2R,3R,5S)-3-hydroxy-5-[(1R)-1-hydroxypropyl]tetrahydrofuran-2-yl]-6H-thiazolo[4,5-d]pyrimidine-2,7-dione, having the following structure:
- or a pharmaceutically acceptable salt thereof.
A compound that is 5-amino-3-[(2R,3R,5S)-3-hydroxy-5-[(1S)-1-hydroxypropyl]tetrahydrofuran-2-yl]-6H-thiazolo [4,5-d]pyrimidine-2,7-dione, having the following structure:
- or a pharmaceutically acceptable salt thereof.
A compound that is [(2R,3R,5S)-2-(5-amino-2,7-dioxo-6H-thiazolo[4,5-d]pyrimidin-3-yl)-5-[(1R)-1-hydroxypropyl]tetrahydrofuran-3-yl] acetate, having the following structure:
- or a pharmaceutically acceptable salt thereof.
A compound that is [(2R,3R,5S)-2-(5-amino-2,7-dioxo-6H-thiazolo [4,5-d]pyrimidin-3-yl)-5-[(1S)-1-hydroxypropyl]tetrahydrofuran-3-yl] acetate, having the following structure:
- or a pharmaceutically acceptable salt thereof.
A compound that is [(1S)-1-[(2S,4R,5R)-5-(5-amino-2,7-dioxo-6H-thiazolo[4,5-d]pyrimidin-3-yl)-4-hydroxy-tetrahydrofuran-2-yl]propyl]acetate, having the following structure:
- or a pharmaceutically acceptable salt thereof.
A compound that is 5-amino-3-[(2R,3R,5S)-3-hydroxy-5-[(1R)-1-hydroxybutyl]tetrahydrofuran-2-yl]-6H-thiazolo[4,5-d]pyrimidine-2,7-dione, having the following structure:
- or a pharmaceutically acceptable salt thereof.
A compound that is 5-amino-3-[(2R,3R,5S)-3-hydroxy-5-[(1S)-1-hydroxybutyl]tetrahydrofuran-2-yl]-6H-thiazolo[4,5-d]pyrimidine-2,7-dione, having the following structure:
- or a pharmaceutically acceptable salt thereof.
A compound that is [(1S)-1-[(2S,4R,5R)-5-(5-amino-2,7-dioxo-6H-thiazolo[4,5-d]pyrimidin-3-yl)-4-hydroxy-tetrahydrofuran-2-yl]propyl] 2-methylpropanoate, having the following structure:
- or a pharmaceutically acceptable salt thereof.
A substantially diastereomerically pure compound of formula (IIa),
- wherein
- R4 is hydroxy or C1-6alkylcarbonyl-O—;
- R5 is C1-6alkyl or C3-7cycloalkyl;
- and
- R6 is hydrogen or C1-6alkylcarbonyl;
- or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof.
A compound that is 5-amino-3-[(2R,3R,5S)-3-hydroxy-5-[(1R)-1-hydroxypropyl]tetrahydrofuran-2-yl]thiazolo[4,5-d]pyrimidin-2-one, having the following structure:
- or a pharmaceutically acceptable salt thereof.
A compound that is 5-amino-3-[(2R,3R,5S)-3-hydroxy-5-[(1S)-1-hydroxypropyl]tetrahydrofuran-2-yl]thiazolo[4,5-d]pyrimidin-2-one, having the following structure:
- or a pharmaceutically acceptable salt thereof.
A compound that is [(2R,3R,5S)-2-(5-amino-2-oxo-thiazolo[4,5-d]pyrimidin-3-yl)-5-[(1R)-1-hydroxypropyl]tetrahydrofuran-3-yl] acetate, having the following structure:
- or a pharmaceutically acceptable salt thereof.
A compound that is [(2R,3R,5S)-2-(5-amino-2-oxo-thiazolo[4,5-d]pyrimidin-3-yl)-5-[(1S)-1-hydroxypropyl]tetrahydrofuran-3-yl] acetate, having the following structure:
- or a pharmaceutically acceptable salt thereof.
A compound that is [(1R)-1-[(2S,4R,5R)-5-(5-amino-2-oxo-thiazolo[4,5-d]pyrimidin-3-yl)-4-hydroxy-tetrahydrofuran-2-yl]propyl] acetate, having the following structure:
- or a pharmaceutically acceptable salt thereof.
A compound that is [(1S)-1-[(2S,4R,5R)-5-(5-amino-2-oxo-thiazolo [4,5-d]pyrimidin-3-yl)-4-hydroxy-tetrahydrofuran-2-yl]propyl] acetate, having the following structure:
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.