6-alkenyl-, 6-alkinyl- and 6-epoxy-epothilone derivatives,...

C - Chemistry – Metallurgy – 07 – D

Patent

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C07D 493/04 (2006.01) A61K 31/335 (2006.01) C07D 405/04 (2006.01) C07D 405/06 (2006.01) C07D 405/14 (2006.01) C07D 413/04 (2006.01) C07D 413/06 (2006.01) C07D 413/14 (2006.01) C07D 417/04 (2006.01) C07D 417/06 (2006.01) C07D 417/14 (2006.01)

Patent

CA 2371226

This invention describes the new 6-alkenyl- and 6-alkinyl- epothilone derivatives of general formula (I) in which R1a, R1b, R2a, R3a, R3b, R4, R5, R6, R7, A, Y, D, E, G, Y and Z have the meanings that are indicated in the description. The new compounds interact with tubulin by stabilizing microtubuli that are formed. They are able to influence the cell-splitting in a phase-specific manner and thus find use in treating diseases or conditions associated with the need for cell growth, division and/or proliferation. Thus the compounds are suitable for treating malignant tumors, for example, ovarian, stomach, colon, adeno-, breast, lung, head and neck carcinomas, malignant melanoma, acute lymphocytic and myelocytic leukemia. In addition, they are suitable for anti-angiogenesis therapy as well as for treatment of chronic inflammatory diseases (such as psoriasis, arthritis). Methods of use and preparation of the compounds are also described.

L'invention concerne de nouveaux dérivés 6-alcényl- et 6-alkinyl-épothilone de formule générale (I), dans laquelle R?1a¿, R?1b¿, R?2a¿, R?3a¿, R?3b¿, R?4¿, R?5¿, R?6¿, R?7¿, A, Y, D, E, G, Y et Z sont tels que définis dans le descriptif. Les nouveaux composés interagissent avec la tubuline pour stabiliser les microtubules qui sont formées. Ils peuvent avoir une influence sur la division cellulaire d'une manière spécifique à une phase et trouvent ainsi une application dans le traitement de maladies ou de conditions associées au besoin de croissance, de division et/ou de prolifération cellulaire. Les composés sont donc appropriés dans le traitement de tumeurs malignes, telles que des carcinomes de l'ovaire, de l'estomac, du côlon, du sein, du poumon, de la tête, du cou ou des adéno-carcinomes, des mélanomes malins, une leucémie lymphocytique ou myélocytaire aiguë. Les composés sont en outre appropriés dans la thérapie anti-angiogénèse ainsi que dans le traitement de maladies inflammatoires chroniques (telles que le psoriasis ou l'arthrite). L'invention concerne également des méthodes d'utilisation et de préparation des composés.

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