Prodrugs of phosphonate nucleotide analogues and methods for...

C - Chemistry – Metallurgy – 07 – F

Patent

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C07F 9/6561 (2006.01) A61K 31/675 (2006.01) A61P 31/12 (2006.01) A61P 35/00 (2006.01) C12Q 1/02 (2006.01) C12Q 1/18 (2006.01) G01N 33/50 (2006.01) G01N 33/53 (2006.01) C07H 19/10 (2006.01) C07H 19/20 (2006.01)

Patent

CA 2416757

A novel method is provided for screening prodrugs of methoxyphosphonate nucleotide analogues to identify prodrugs selectively targeting desired tissues with antiviral or antitumor activity. This method has led to the identification of novel mixed ester-amidates of PMPA for retroviral or hepadnaviral therapy, including compounds of structure (5a) having substituent groups as defined herein. Compositions of these novel compounds in pharmaceutically acceptable excipients and their use in therapy and prophylaxis are provided. Also provided is an improved method for the use of magnesium alkoxide for the preparation of starting materials and compounds for use herein.

L'invention concerne une nouvelle méthode d'identification de promédicaments à base d'analogues nucléotidiques de méthoxyphosphonate permettant d'identifier des promédicaments conférant de façon sélective une activité antivirale o antitumorale à des tissus désirés. Cette méthode permet d'identifier de nouveaux mélanges ester-amidates de PMPA pour une thérapie rétrovirale ou du virus ADN de l'hépatite, y compris des composés représentés par la structure générale (5a) comprenant des groupes de substitution tel qu'ils sont définis dans l'invention. L'invention concerne également des compositions de ces nouveaux composés dans des excipients pharmaceutiquement acceptables et leur utilisation dans la thérapie et la prévention. L'invention concerne également une méthode améliorée d'utilisation d'alcoxyde de magnésium pour la préparation de produits et de composés de départ destinés à être utilisés dans ladite méthode.

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