# US 2019/0169222 A1 · Novel 3-substituted 5-amino-6h-thiazolo[4,5-d]pyrimidine-2, 7-dione compounds for the treatment and prophylaxis of virus infection > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2019/0169222 A1 - Document ID: US20190169222A1 - Status: Published application - Kind: A1 - Application number: 16/025,170 - Filed: 2018-07-02 - Published: 2019-06-06 - Earliest claimed: 2014-12-08 - Assignees: Hoffmann-La Roche Inc. - Applicants: Hoffmann-La Roche Inc. - Inventors: Dongdong Chen; Song Feng; Lu Gao; Chao Li; Baoxia Wang; Lisha Wang; Hongying Yun; Xiufang Zheng - Web page: https://patentgrep.com/patent/US20190169222A1 ## CPC - C07H 19/24: Heterocyclic radicals containing oxygen or sulfur as ring hetero atom - A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics - A61P 31/12: Antivirals - A61P 31/14: for RNA viruses - A61P 31/20: for DNA viruses - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07D 513/04: Ortho-condensed systems - C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) ## 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. ## Claims ### Claim at position 1 -36. (canceled) ### Claim 37 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. ### Claim 38 (depends on 36) 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. ### Claim 39 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. ### Claim 40 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. ### Claim 41 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. ### Claim 42 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. ### Claim 43 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. ### Claim 44 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. ### Claim 45 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. ### Claim 46 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. ### Claim 47 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. ### Claim 48 (depends on 47) The substantially diastereomerically pure compound according to claim 47, wherein R4 is hydroxy or acetyloxy; R5 is ethyl or cyclopropyl; and R6 is hydrogen or acetyl; or a pharmaceutically acceptable salt, enantiomer or diastereomer thereof. ### Claim 49 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. ### Claim 50 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. ### Claim 51 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. ### Claim 52 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. ### Claim 53 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. ### Claim 54 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. ### Claim 55 (depends on 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54) A pharmaceutical composition comprising a compound according to any one of claims 37 to 54, or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier. ### Claim 56 (depends on 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54) A method for treating a Hepatitis B virus infection comprising administering to a patient in need thereof a therapeutically effective amount of a compound according to any one of claims 37 to 54, or a pharmaceutically acceptable salt thereof. ### Claim 57 (depends on 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54) A method of activating the TLR7 receptor in a patient in need thereof comprising administering an effective amount of a compound according to any one of claims 37 to 54, or a pharmaceutically acceptable salt thereof. ### Claim 58 (depends on 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54) A method of stimulating production of interferon-a comprising administering to a patient in need thereof a therapeutically effective amount of a compound any one of claims 37 to 54, or a pharmaceutically acceptable salt thereof.