New taxoids, preparation thereof and pharmaceutical...

C - Chemistry – Metallurgy – 07 – D

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C07D 305/14 (2006.01) A61K 31/33 (2006.01) C07D 407/12 (2006.01) C07D 409/12 (2006.01) C07D 417/12 (2006.01)

Patent

CA 2190651

New taxoids having general formula (I), (II) preparation thereof and pharmaceutical compositions containing them. In general formula (I): R¿a? is hydrogen, hydroxy, alkoxy, acyloxy, alkoxyacetoxy, and R¿b? is hydrogen or R¿a? and R¿b? form together with the carbon atom to which they are linked a ketone function, Z is a hydrogen atom or a radical having general formula (II) wherein R¿1? is an optionally substituted benzoyl radical, a thenyl or furoyl radical or a radical R¿2?-O-CO- wherein R¿2? is an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, optionally substituted phenyl or heterocyclyl radical; R¿3? is an alkyl, alkenyl, alkynyl, cycloalkyl, phenyl, naphtyl or heterocyclic aromatic radical, and R¿4? and R¿5?, similar or different, represent an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, aryl or heterocyclyl radical, with the condition that R¿5? does not represent a methyl radical. The new products having general formula (I) wherein Z is a radical having general formula (II) have remarkable antitumoral and antileukaemic properties.

Nouveaux taxoïdes de formules générales (I), (II), leur préparation et les compositions pharmaceutiques qui les contiennent. Dans la formule générale (I): Ra représente hydrogène, hydroxy, alcoxy, acyloxy, alcoxyacétoxy et Rb représente hydrogène ou bien Ra et Rb forment ensemble avec l'atome de carbone auquel ils sont liés une fonction cétone; Z représente un atome d'hydrogène ou un radical de formule générale (II) dans laquelle R1 représente un radical benzoyle éventuellement substitué, thénoyle ou furoyle ou un radical R2-O-CO- dans lequel R2 représente un radical alcoyle, alcényle, alcynyle, cycloalcoyle, cycloalcényle, bicycloalcoyle, phényle éventuellement substitué ou hétérocyclyle; R3 représente un radical alcoyle, alcényle, alcynyle, cycloalcoyle, phényle, naphtyle ou hétérocyclique aromatique; et R4 et R5, identiques ou differents, représentent un radical alcoyle, alcényle, alcynyle, cycloalcoyle, cycloalcényle, bicycloalcoyle, aryle, ou hétérocyclyle, R5 ne pouvant pas représenter un radical méthyle. Les nouveaux produits de formule générale (I) dans laquelle Z représente un radical de formule générale (II) présentent des propriétés antitumorales et antileucémiques remarquables.

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