Immunosuppresive effects of pteridine derivatives

Abstract

Novel poly-substituted pteridinediones (lumazines), and mono- or polysubstituted 2-thiolumazines, 4-thiolumazines or 2,4-dithiolumazines, having disclosed substituents in positions 1, 3, 6 and 7 of the pteridine ring, and pharmaceutically acceptable salts thereof, are useful as biologically active ingredients in preparing pharmaceutical compositions especially for the treatment or prevention of a CNS disorder, a cell proliferative disorder, a viral infection, an immune or auto-immune disorder or a transplant rejection. Combinations of the pteridine derivatives of the invention with an immunosuppressant or immunomodulator drug, an antineoplastic drug or an antiviral agent, providing potential synergistic effects, are also disclosed.

Description

[0001] The invention relates to a class of novel poly-substituted pteridine-2,4-diones (lumazines), as well as novel mono- and polysubstituted 2-thiolumazines, 4-thiolumazines and 2,4-dithiolumazines. The invention further relates to pharmaceutical compositions including a broad class of poly-substituted pteridine-2,4-diones (lumazines), as well as mono- and polysubstituted 2-thiolumazines, 4-thiolumazines and 2,4-dithiolumazines especially for the prevention and / or the treatment of pathologic conditions such as, but not limited to, immune and autoimmune disorders, organ and cells transplant rejections, cell proliferative disorders, cardiovascular disorders, disorders of the central nervous system and viral diseases. [0002] The invention further relates to combined pharmaceutical preparations comprising one or more polysubstituted pteridine-2,4-diones (lumazines), as well as mono- and polysubstituted 2-thiolumazines, 4-thiolumazines and 2,4-dithiolumazines and one or more known immu...

AI Technical Summary

Benefits of technology

"The present invention relates to a group of novel compounds, including poly-substituted pteridine-2,4-diones, mono- and poly-substituted 2-thiolumazines, 4-thiolumazines, and 2,4-dithiolumazines, as well as their pharmaceutically acceptable salts and enantiomers. These compounds have various pharmaceutical activities and can be used for the treatment of various diseases. The invention also includes methods for their synthesis and pharmaceutical compositions containing these compounds."

Problems solved by technology

Since these drugs affect mitosis and cell division, they have severe toxic effects on normal cells with high turn-over rate such as bone marrow cells and the gastrointestinal tract lining.

Accordingly, marrow depression and liver damage are common side effects.

The common side effects observed with the use of these compounds are frequent infections, abnormal metabolism, hypertension, and diabetes.

However, cyclosporines suffer from a small therapeutic dose window and severe toxic effects including nephrotoxicity, hepatotoxicity, hypertension, hirsutism, cancer, and neurotoxicity.

Another such drug, mitoxantrone, is known to induce heart and kidney toxicity.

Introduction of such monoclonal antibodies into a patient, as with many biological materials, induces several side-effects, such as dyspnea.

However, such ideal matches are difficult to achieve.

Further, with the increasing need of donor organs an increasing shortage of transplanted organs currently exists.

Accordingly, xenotransplantation has emerged as an area of intensive study, but faces many hurdles with regard to rejection within the recipient organism.

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