Method for dosing therapeutic compounds

Details Method for dosing therapeutic compounds Method for dosing therapeutic compounds

C - Chemistry, Metallurgy

07

K

C07K 2/00 (2006.01) A61K 31/66 (2006.01) A61K 31/70 (2006.01) A61K 38/02 (2006.01) A61K 38/05 (2006.01) C07F 9/6512 (2006.01) C07F 9/6561 (2006.01) C07F 9/6571 (2006.01) C07F 9/6574 (2006.01) C07F 9/6578 (2006.01) C07H 13/00 (2006.01) C07H 19/10 (2006.01) C07H 19/20 (2006.01) C07J 9/00 (2006.01) C07K 5/06 (2006.01)

Patent

CA 2171868

The internally cyclized congeners of hydroxy-substituted nucleotide analogues have been found to exhibit substantially lower toxicity in vivo than their uncyclized analogues, while retaining essentially the same antiviral activity. This was unexpected because the prior art would have suggested that the cyclic analogues offered no significant advantages in respect to toxicity in vivo. This finding permits the administration of much greater doses of the cyclic congeners than otherwise would have been possible and/or allows the clinician to omit toxicity ameliorating interventions. Novel compounds are provided for use in the method of this invention. Novel methods for the preparation of these compounds also are provided.

Il a été découvert que les congénères à cyclisation interne d'analogues nucléotidiques substitués par hydroxy présentent une toxicité in vivo sensiblement inférieure à leurs analogues non cyclisés, tout en retenant la même activité antivirale. Il s'agit là d'une découverte inattendue dans la mesure où la technique actuelle aurait plutôt suggéré que les analogues cycliques ne présentaient pas d'avantages appréciables en ce qui concerne la toxicité in vivo. Cette découverte permet d'administrer des doses beaucoup plus élevées des congénères cycliques que cela n'aurait autrement été possible, et/ou permet au clinicien d'éviter les interventions visant à amoindrir la toxicité. De nouveaux composés utilisés selon le procédé de l'invention sont également décrits, ainsi que de nouveaux procédés de préparation de ces composés.

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