Compounds useful for the treatment of cancer, compositions thereof and methods therewith

Abstract

The present invention generally relates to compounds and compositions useful for the modulation of ligase activity. The invention further relates to Compounds of the Invention, compositions thereof, and methods for treating or preventing cancer, a neoplastic disorder, acute or chronic renal failure, an inflammatory disorder, an immune disorder, a cardiovascular disease, an effect of aging or an infectious disease comprising administering an effective amount of a Compound of the Invention. The invention further relates to the use of a Compound of the Invention as a preservative of a cell, blood, tissue or an organ or as an agent to modulate stem cells.

Description

[0001] This application is a division of U.S. application Ser. No. 10 / 463,009, filed Jun. 16, 2003, allowed, which claims the priority benefit of U.S. application No. 60 / 389,461, filed Jun. 17, 2002, the disclosure of each of which is incorporated by reference herein in its entirety.1. FIELD OF THE INVENTION [0002] The present invention generally relates to novel compounds and pharmaceuticals compositions useful for the modulation of ligase activity. The invention further relates to methods for treating or preventing cancer, a neoplastic disorder, acute or chronic renal failure, an inflammatory disorder, an immune disorder, a cardiovascular disease, an effect of aging or an infectious disease comprising administering an effective amount of a Compound of the Invention to a patient in need thereof. The invention further relates to the use of a Compound of the Invention as a preservative of a cell, blood, tissue or an organ or as an agent to modulate stem cells. 2. BACKGROUND OF THE IN...

AI Technical Summary

Benefits of technology

[0014] The Compounds of the Invention and compositions thereof are useful for modulating ligase activity; treating or preventing a disease responsive to the modulation of ligase activity; treating or preventing a disease responsive to the inhibition of ligase activity; treating or preventing a disease responsive to the activation of ligase activity; modulating E3 ubiquitin-protein ligase activity; modulating E3 ubiquitin-protein ligase mediated ubiquitination of p27 / Kip1; modulating cellular p27 / Kip1; arresting the growth of a cell; treating or preventing side-effects associated with chemotherapy or radiation therapy; increasing the lifetime of a cell, blood, tissue, an organ or an organism that is cryopreserved; regulating and controlling the differentiation and maturation of mammalian, particularly human stem cells along specific cell and tissue lineages, in particular, to the differentiation of embryonic-like stem cells originating from a postpartum placenta or for the differentiation of stem cells isolated form sources such as cord blood; treating or preventing cancer or neoplastic disease in a patient in need of such treatment or prevention; or inhibiting the growth of a cancer cell or neoplastic cell.

Problems solved by technology

As much as 60% of stored human blood and blood-products can be lost due to the limited “shelf-life”.

All of these approaches pose significant drawbacks for the patient.

Surgery, for example, may be contraindicated due to the health of the patient or may be unacceptable to the patient.

Additionally, surgery may not completely remove the neoplastic tissue.

Radiation therapy is effective only when the irradiated neoplastic tissue exhibits a higher sensitivity to radiation than normal tissue, and radiation therapy can also often elicit serious side effects.

However, despite the availability of a variety of chemotherapeutic agents, chemotherapy has many drawbacks (see, for example, Stockdale, 1998, “Principles Of Cancer Patient Management” in Scientific American Medicine, vol.

Almost all chemotherapeutic agents are toxic, and chemotherapy causes significant, and often dangerous, side effects, including severe nausea, diarrhea, bone marrow depression, immunosuppression, etc.

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