Sphingolipid derivatives and their methods of use

Details Sphingolipid derivatives and their methods of use Sphingolipid derivatives and their methods of use

C - Chemistry, Metallurgy

07

H

C07H 15/10 (2006.01) A61K 31/66 (2006.01) A61K 31/70 (2006.01) C07F 9/08 (2006.01) C07F 9/09 (2006.01) C07F 9/113 (2006.01) C07F 9/141 (2006.01) C07F 9/143 (2006.01) C07F 9/22 (2006.01)

Patent

CA 2320117

Derivatives of sphingolipids of formula (I) are provided wherein the substituents are as defined in the specification and wherein there is at least one R2 substituent in the sphingolipid derivative. The compounds are useful in the treatment of abnormal cell proliferation, including benign and malignant tumors, the promotion of cell differentiation, the induction of apoptosis, the inhibition of protein kinase C, and the treatment of inflammatory conditions, psoriasis, inflammatory bowel disease as well as proliferation of smooth muscle cells in the course of development of plaques in vascular tissue. The invention also includes a method for triggering the release of cytochrome c from mitochondria that includes administering an effective amount of a sphingolipid or its derivative or prodrug to a host in need thereof. Further, the invention provides a method for treating bacterial infections, including those that influence colon cancer and other disorders of the intestine, that includes administering an effective amount of one of the active compounds identified herein.

L'invention concerne des dérivés de sphingolipides représentés par la formule (I), les substituants étant tels que définis dans l'invention. Aux fins de ladite formule, les dérivés considérés comportent au moins un substituant R?2¿. Ces composés sont utiles pour le traitement de la prolifération cellulaire anormale, y compris les tumeurs bénignes et malignes, l'augmentation de la différenciation cellulaire, l'induction de l'apoptose, l'inhibition de la protéine kinase C, le traitement des états inflammatoires, du psoriasis et de l'affection intestinale inflammatoire, et aussi la prolifération de cellules musculaires lisses au cours du développement des plaques de lyse dans le tissu vasculaire. L'invention concerne également un procédé permettant de déclencher la libération de cytochrome c depuis les mitochondries, qui consiste à administrer une quantité efficace de sphingolipide ou un dérivé de sphingolipide à l'hôte ayant besoin de recevoir ce type de substance. L'invention concerne en outre un procédé relatif au traitement des affections bactériennes, y compris celles qui ont une incidence sur le cancer du colon et autres maladies de l'intestin, ledit procédé consistant à administrer une quantité efficace de l'un des composés actifs identifiés.

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