3,5-disubstituted and 3,5,7-trisubstituted-3H-oxazolo and 3H-thiazolo[4,5-d]pyrimidin-2-one compounds and prodrugs thereof
Inventors
Webber, Stephen E. • Haley, Gregory J. • Lennox, Joseph R. • Xiang, Alan Xin • Rueden, Erik J.
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-8883758-B2
Publication Date
2014-11-11
Expiration Date
Abstract
The invention is directed to 3,5-disubstituted and 3,5,7-trisubstituted-3H-oxazolo and 3H-thiazolo[4,5-d]pyrimidin-2-one compounds and prodrugs thereof that have immunomodulatory activity. The invention is also directed to the therapeutic or prophylactic use of such compounds and pharmaceutical compositions containing them, and to methods of treating diseases and disorders described herein, by administering effective amounts of such compounds and prodrugs.
Core Innovation
The invention relates to Formula I and Formula II compounds, including 3H-oxazolo and 3H-thiazolo[4,5-d]pyrimidin-2-one compounds and thiazolo[4,5-d]pyrimidin-2-one nucleosides. The compounds include 3,5-disubstituted and 3,5,7-trisubstituted members, ribosyl and deoxyribosyl derivatives, and Formula I prodrugs, with pharmaceutically acceptable salts, solvates, hydrates, pharmaceutically active metabolites, stereoisomers, and tautomeric forms.
The disclosed framework supports administering such compounds to a patient in treatment and prevention contexts. The methods use therapeutically effective amounts and, where applicable, prophylactically effective amounts, and are directed to hepatitis C virus therapy, including treatment and prevention of viral diseases such as hepatitis C virus and hepatitis B virus.
The invention also describes treatment of tumors or cancers caused by hepatitis C virus by administering a therapeutically effective amount of the disclosed compounds, optionally in combination with additional antiviral, anti-tumor, or other therapeutic agents. The disclosure further states immunomodulatory activity and immune system enhancement, including modulation of natural killer cells, macrophages, dendritic/lymphocyte cells, Th1/Th2 cytokines, and interferons.
Claims Coverage
The independent claims cover hepatitis C virus-caused tumor or cancer treatment by administering a therapeutically effective amount of a compound from the disclosed class, including pharmaceutically acceptable salts and/or tautomers. Across the independent claims, the inventive features center on the compound class, hepatitis C virus specificity, and optional co-administration and dosage form limitations.
Treating hepatitis C virus-caused cancer with a selected compound
A method of treating a tumor or cancer caused by a virus wherein the virus is hepatitis C, comprising administering to a patient a therapeutically effective amount of a compound selected from the disclosed compound class, or a pharmaceutically acceptable salt or tautomer thereof.
Hepatitis C virus-specific therapeutic agent co-administration
Further administering to the patient a hepatitis C virus-specific therapeutic agent that exhibits anti-hepatitis C virus activity.
Therapeutic agent selected from listed drug classes
Further administering to the patient a therapeutically effective amount of a therapeutic agent selected from antibiotics, antiemetic agents, antidepressants, antifungal agents, anti-inflammatory agents, antiviral agents, anticancer agents, immunomodulatory agents, β-interferons, alkylating agents, hormones, and cytokines.
Oral or parenteral dosage forms
Specifying that the compound is administered in an oral or parenteral dosage form.
Across the independent claims, the patent claims treatment of hepatitis C virus-caused tumors or cancers by administering therapeutically effective amounts of a compound of the disclosed structural class, including pharmaceutically acceptable salts and/or tautomers. Dependent claim refinements add hepatitis C virus-specific therapeutic agents, broader therapeutic-agent classes, and oral or parenteral dosage forms.
Stated Advantages
Oral availability.
Lymphoid-tissue activation masking/tolerability.
Immunomodulatory activity.
Improved activity ranges for IFN-α induction relative to isatoribine, with specific compounds reported as outperforming isatoribine.
Documented Applications
Therapeutic or prophylactic treatment of hepatitis C virus (HCV) infection.
Treatment and prevention of hepatitis C virus and hepatitis B virus, and additional viruses.
Treatment of tumors or cancers caused by hepatitis C virus in a patient by administering a therapeutically effective amount of the disclosed compounds, optionally in combination with additional antiviral, anti-tumor, or other therapeutic agents.
Immune system enhancement via modulation of natural killer cells, macrophages, and dendritic/lymphocyte cells, including Th1/Th2 cytokine modulation and interferon induction.
Antiviral and immune activity evaluation in PBMCs, including measurement of IFN-α induction by ELISA, with comparison to isatoribine.
Interested in licensing this patent?