Novel polyamine analogues as therapeutic and diagnostic agents

C - Chemistry – Metallurgy – 07 – C

Patent

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C07C 233/40 (2006.01) A61K 47/48 (2006.01) C07C 233/36 (2006.01) C07C 233/78 (2006.01) C07C 235/20 (2006.01) C07C 235/34 (2006.01) C07C 235/50 (2006.01) C07C 237/10 (2006.01) C07C 237/20 (2006.01) C07C 237/22 (2006.01) C07C 271/20 (2006.01) C07C 271/22 (2006.01) C07C 275/28 (2006.01) C07C 311/07 (2006.01) C07C 311/10 (2006.01) C07C 311/18 (2006.01) C07C 311/29 (2006.01) C07C 311/41 (2006.01) C07C 323/60 (2006.01) C07D 207/16 (2006.01) C07D 213/82 (2006.01) C07D 215/36 (2006.01) C07D 215/52 (2006.01) C07D 21

Patent

CA 2297413

Novel inhibitors of polyamine transport having inhibition constants two orders of magnitude lower than those of known compounds are disclosed. These polyamine analogues are useful pharmaceutical agents for treating diseases where it is desired to inhibit polyamine transport or other polyamine binding proteins, for example cancer and post-angioplasty injury. Novel chemical synthetic methods to obtain polyamine analogues are disclosed, including the production of a combinatorial polyamine library. These approaches yield analogues with desirable activities both for diagnostic and research assays and therapy. The assays of the invention are useful for high throughput screening of targets in the discovery of drugs that interact with the polyamine system.

La présente invention concerne des inhibiteurs du transport de la polyamine présentant des constantes d'inhibition inférieures de deux ordres de grandeur à celles des composés connus. Ces analogues de la polyamine constituent des agents pharmaceutiques utiles pour le traitement des maladies où l'on désire inhiber le transport de la polyamine ou d'autres protéines liant la polyamine, par exemple le cancer ou les lésions consécutives à une angioplastie. L'invention se rapporte à de nouveaux procédés chimiques synthétiques permettant d'obtenir des analogues de la polyamine, y compris à la production d'une bibliothèque combinatoire de polyamines. Ces procédés permettent d'obtenir des analogues présentant des activités désirables pour le diagnostic, les analyses de recherche et la thérapie. Les analyses de la présente invention sont utilisées pour le criblage à grand débit de cibles permettant de découvrir des médicaments qui interagissent avec le système de la polyamine.

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