Nucleoside compounds and methods of use thereof

Details Nucleoside compounds and methods of use thereof Nucleoside compounds and methods of use thereof

A - Human Necessities

61

K

A61K 31/7064 (2006.01) A61P 35/00 (2006.01) C07H 19/14 (2006.01)

Patent

CA 2609342

The present invention provides methods of utilizing a nucleoside derivative having the chemical formula of Formula (I) to downregulate expression of an anti-apoptotic protein such as survivin in a cell, induce apoptosis in a cell, inhibit angiogenesis in a cell, inhibit binding of p53 to DNA in a cell, inhibit phosphorylation of Akt in a cell and inhibit HIV transcription in a cell, by administering to the cell or tissue an amount of a compound of Formula (I) sufficient to achieve the desired activity. Formula (I): wherein the substituents Ra , Rb , Rc, Rd , Re , Rf , Rg , Rh, Ri and Rk are as defined in the specification. A particularly preferred nucleoside derivative is ARC (4-amino-6-hydrazino-7-beta-D-ribofuranosyl-7H-pyrrolo[2, 3-d]- pyrimidine-5-carboxamide).

La présente invention concerne des procédés pour utiliser un dérivé nucléosidique de formule chimique (I), pour réaliser la sous-régulation de l'expression d'une protéine anti-apoptotique telle que la survivine dans, une cellule, induite l'apoptose dans une cellule, inhiber l'angiogenèse dans une cellule, inhiber la liaison de p53 à l'ADN dans une cellule, inhiber la phosphorylation de Akt dans une cellule, et inhiber la transcription du VIH dans une cellule, par administration à la cellule ou au tissu, d'une quantité d'un composé de formule (I), suffisante pour obtenir l'activité désirée. Dans la formule (I), les substituants Ra, Rb, Rc, Rd, Re, Rf, Rg, Rh, Ri et Rk sont tels que définis dans la spécification. Un dérivé nucléosidique particulièrement préféré est ARC (4-amino-6-hydrazino-7-bêta-D-ribofuranosyl-7H-pyrrolo[2, 3-d]-pyrimidine-5-carboxamide).

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