Immunosuppressive effects of pteridine derivatives

Abstract

This invention relates to a group of trisubstituted and tetrasubstituted pteridine derivatives, their pharmaceutically acceptable salts, N-oxides, solvates, dihydro- and tetrahydroderivatives and enantiomers, possessing unexpectedly desirable pharmaceutical properties, in particular which are highly active immunosuppressive agents, and as such are useful in the treatment in transplant rejection and / or in the treatment of certain inflammatory diseases. These compounds are also useful in preventing or treating cardiovascular disorders, allergic conditions, disorders of the central nervous system and cell proliferative disorders.

Description

CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation-in-part of pending U.S. application Ser. No. 09 / 869,468, filed Oct. 10, 2001, which is the National Stage of International Application No. PCT / EP99 / 10320, filed Dec. 28, 1999, which was published in English under PCT Article 21(2), and which claims the benefit of U.S. provisional application No. 60 / 113,989 filed Dec. 28, 1998; the disclosures of which are incorporated by reference in their entirety. [0002] The invention relates to a class of novel pteridines. The invention further relates to pharmaceutical compositions including a broad class of pteridines especially for the prevention and / or the treatment of pathologic conditions such as, but not limited to, immune and auto-immune disorders, organ and cells transplant rejections, cell proliferative disorders, cardiovascular disorders, disorders of the central nervous system and viral diseases. [0003] The invention further relates to combined pharmaceu...

AI Technical Summary

Benefits of technology

[0030] Compounds of formula (II) are highly active immunosuppressive agents, antineoplastic agents, anti-allergic agents or anti-viral agents which, together with one or more pharmaceutically acceptable carriers, may be formulated into pharmaceutical compositions for the prevention or treatment of pathologic conditions such as, but not limited to, immune and autoimmune disorders, organ and cells transplant rejections, allergic conditions, cell proliferative disorders, cardiovascular disorders, disorders of the central nervous system and viral diseases.

[0031] In a further embodiment, the present invention r

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 of these antiproliferative drugs.

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.

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.

Invasion of lymphatic vessels results in metastasis to regional draining lymph nodes.

Presently, to our knowledge, no treatment is capable of preventing or significantly reducing metastasis.

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