Highly lipophilic camptothecin derivatives

C - Chemistry – Metallurgy – 07 – D

Patent

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Details

C07D 491/22 (2006.01) A01N 43/42 (2006.01) C07D 209/56 (2006.01) C07D 491/00 (2006.01) C07F 7/08 (2006.01)

Patent

CA 2280905

Novel camptothecin compounds having the general formula: (see formula I) wherein: R1 is selected from: acyl, C2-C8 alkenyl, or C2-C8 alkynyl, optionally substituted by one or more halogen atoms or OR9 or lower alkyl for a corresponding hydrogen atom therein; oxo; arylalkenyl; arylalkynyl; heterocycle; -S(O)-lower alkyl; and -lower alkyl-P (O) R6R, or -X- (C0-C6 alkyl , C0-C9 alkenyl , or C0-C8 alkynyl) -SiR8R9R10; R2 is hydrogen, halo, lower alkyl, amino or nitro; R4 is hydrogen or lower alkyl; R6 and R7 are each individually hydrogen or lower alkyl; R8, R9 and R10 are each individually hydrogen or lower alkyl; R11 is hydrogen, hydroxy or acetoxy; and X is sulfur or X is absent. The invention also includes the use of these compounds as Topoisomerase I inhibitors to treat patients with cancer. The invention also includes pharmaceutical compositions which consist of the novel compounds in solution or suspension with one or more pharmaceutical acceptable carriers.

Cette invention porte sur de nouveaux dérivés de camptothécine, et notamment sur des dérivés ayant une substitution à la position C-7 ou à au moins une des positions C-9, C-10, C-11 ou C-12, ou sur des dérivés disubstitués ayant une première substitution en C-7 et une seconde au niveau d'une des positions C-9, C-10, C-11 ou C-12. Cette invention porte également sur des procédés d'utilisation des composés agissant comme inhibiteurs de Topoisomérase I pour traiter les patients atteints d'un cancer. Cette invention porte encore sur des formulations pharmaceutiques comprenant les nouveaux composés dans une solution ou une suspension avec un ou plusieurs excipients ou diluants pharmaceutiques.

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