# US 7,745,415 B2 · 3-β-D-ribofuranosylthiazolo[4,5-d]pyrimidine nucleosides and uses thereof

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- Number: US 7,745,415 B2
- Document ID: US7745415B2
- Status: Granted
- Kind: B2
- Application number: 12/015,821
- Filed: 2008-01-17
- Published: 2008-10-16
- Granted: 2010-06-29
- Earliest claimed: 2001-11-27
- Assignees: Anadys Pharmaceuticals, Inc.
- Inventors: Devron R. Averett; Stephen E. Webber; Joseph R. Lennox; Erik J. Rueden
- Web page: https://patentgrep.com/patent/US7745415B2

## CPC

- C07H 19/24: Heterocyclic radicals containing oxygen or sulfur as ring hetero atom
- A61P 31/12: Antivirals
- A61P 31/14: for RNA viruses
- 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

## Abstract

The invention is directed to 3-β-D-ribofuranosylthiazolo[4,5-d]pyrimidine nucleosides and pharmaceutical compositions containing such compounds that have immunomodulatory activity. The invention is also directed to the therapeutic or prophylactic use of such compounds and compositions, and to methods of treating diseases and disorders described herein, by administering effective amounts of such compounds.

## Claims

### Claim 1

A method of increasing plasma levels of interferon comprising administering to a patient a compound represented by Formula I
wherein:
R1a, R1b, and R1c are independently H, —C(O)R3, a racemic, L-, or D- amino acid group —C(O)CH2NHR4, —C(O)CH(C1-6 alkyl)NHR4, or R1b and R1c are collectively —C(O)—, which together with the oxygen atoms forms a five-membered carbonate ring;
R2 is H;
R3 is a C1-18 alkyl; and
R4 is H, —C(O)CH(C1-6 alkyl)NH2, or —C(O)CH(CH2-aryl)NH2;
wherein the alkyl and aryl moieties of the foregoing groups are optionally substituted with substituents independently selected from halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, hydroxy, C1-C6 alkoxy, —NH2, —NH-alkyl, —N(alkyl)2, —NH-aryl, —N(alkyl)(aryl), —N(aryl)2, —NHCHO, —NHC(O)alkyl, —NHC(O)aryl, —N(alkyl)C(O)H, —N(alkyl)C(O)alkyl, —N(aryl)C(O)H, —N(aryl)C(O)alkyl, —NHCO2alkyl, —N(alkyl)CO2alkyl, —NHC(O)NH2, —N(alkyl)C(O)NH2, —NHC(O)NH-alkyl, —NHC(O)N(alkyl)2, —N(alkyl)C(O)NH-alkyl, N(alkyl)C(O)N(alkyl)2, —NHSO2-alkyl, —N(alkyl)SO2-alkyl, —C(O)alkyl, —C(O)aryl, —OC(O)alkyl, —OC(O)aryl, —CO2-alkyl, —CO2-aryl, —CO2H, —C(O)NH2, —C(O)NH-alkyl, —C(O)N(alkyl)2, —C(O)NH-aryl, —C(O)N(aryl)2, —C(O)N(alkyl)(aryl), —S(O)alkyl, —S(O)aryl, —SO2alkyl, —SO2aryl, —SO2NH2, —SO2NH-alkyl, and —SO2N(alkyl)2;
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The method of claim 1, wherein
R1a, R1b, and R1c are independently H, —C(O)R3, a racemic, L-, or D- amino acid group —C(O)CH(C1-6 alkyl)NH2; and
R3 is a C1-18 alkyl.

### Claim 3 (depends on 1)

The method of claim 1, wherein
R1a, R1b, and R1c are independently H, —C(O)R3, a racemic, L-, or D- amino acid group —C(O)CH(CH(CH3)2)NH2; and
R3 is CH3.

### Claim 4 (depends on 1)

The method of claim 1, wherein
R1a, R1b, and R1c are independently H or —C(O)R3; and
R3 is CH3.

### Claim 5 (depends on 1)

The method of claim 1, wherein
R1a is H and R1b and R1c are —C(O)R3; and
R3 is CH3.

### Claim 6 (depends on 1)

The method of claim 1, wherein the compound is:
or pharmaceutically acceptable salt thereof.

### Claim 7

A method of treating Hepatitis C virus infection comprising administering to a patient infected with hepatitis C virus a therapeutically effective amount of compound represented by Formula I
wherein:
R1a, R1b, and R1c are independently H, —C(O)R3, a racemic, L-, or D- amino acid group —C(O)CH2NHR4, —C(O)CH(C1-6 alkyl)NHR4, or R1b and R1c are collectively —C(O)—, which together with the oxygen atoms forms a five-membered carbonate ring;
R2 is H;
R3 is a C1-18 alkyl; and
R4 is H, —C(O)CH(C1-6 alkyl)NH2, or —C(O)CH(CH2-aryl)NH2;
wherein the alkyl and aryl moieties of the foregoing groups are optionally substituted with substituents independently selected from halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, hydroxy, C1-C6 alkoxy, —NH2, —NH—alkyl, —N(alkyl)2, —NH-aryl, —N(alkyl)(aryl), —N(aryl)2, —NHCHO, —NHC(O)alkyl, —NHC(O)aryl, —N(alkyl)C(O)H, —N(alkyl)C(O)alkyl, —N(aryl)C(O)H, —N(aryl)C(O)alkyl, —NHCO2alkyl, —N(alkyl)CO2alkyl, —NHC(O)NH2, —N(alkyl)C(O)NH2, —NHC(O)NH-alkyl, —NHC(O)N(alkyl)2, —N(alkyl)C(O)NH-alkyl, N(alkyl)C(O)N(alkyl)2, —NHSO2-alkyl, —N(alkyl)S02-alkyl, —C(O)alkyl, —C(O)aryl, —OC(O)alkyl, —OC(O)aryl, —CO2-alkyl, —CO2-aryl, —CO2H, —C(O)NH2, —C(O)NH-alkyl, —C(O)N(alkyl)2, —C(O)NH-aryl, —C(O)N(aryl)2, —C(O)N(alkyl)(aryl), —S(O)alkyl, —S(O)aryl, —SO2alkyl, —SO2aryl, —SO2NH2, —SO2NH-alkyl, and —SO2N(alkyl)2;
or a pharmaceutically acceptable salt thereof.

### Claim 8 (depends on 7)

The method of claim 7, wherein
R1a, R1b, and R1c are independently H, —C(O)R3, a racemic, L-, or D- amino acid group —C(O)CH(C1-6 alkyl)NH2; and
R3 is a C1-18 alkyl.

### Claim 9 (depends on 7)

The method of claim 7, wherein
R1a, R1b, and R1c are independently H, —C(O)R3, a racemic, L-, or D- amino acid group —C(O)CH(CH(CH3)2)NH2; and
R3 is CH3.

### Claim 10 (depends on 7)

The method of claim 7, wherein
R1a, R1b, and R1c are independently H or —C(O)R3; and
R3 is CH3.

### Claim 11 (depends on 7)

The method of claim 7, wherein
R1a is H and R1b and R1c are —C(O)R3; and
R3 is CH3.

### Claim 12

A method of treating Hepatitis C virus infection comprising administering to a patient infected with hepatitis C virus a therapeutically effective amount of a compound represented by the following formula:
or pharmaceutically acceptable salt thereof.