Novel compounds

C - Chemistry – Metallurgy – 07 – D

Patent

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Details

C07D 225/06 (2006.01) A61K 31/395 (2006.01) A61P 35/00 (2006.01)

Patent

CA 2679224

According to the invention there are provided derivatives of a C21-deoxy ansamycin or salt thereof which contain a 1-hydroxyphenyl moiety bearing at position 3 an aminocarboxy substituent, in which position 5 and the aminocarboxy substituent at position 3 are connected by an aliphatic chain of varying length characterised in that the 1-hydroxy position of the phenyl ring is derivatised by an aminoalkyleneaminocarbonyl group, which alkylene group (which may optionally be substituted by alkyl groups) has a chain length of 2 or 3 carbon atoms, a phosphoric acid, or a phosphoric acid ester (such as an alkyl ester) group, or a salt thereof, and which derivatising group increases the water solubility and/or the bioavailability of the parent molecule. Such compounds are useful in therapy eg in the treatment of cancer and B-cell malignancies.

L'invention concerne des dérivés d'une C21-désoxy ansamycine ou d'un sel de cette dernière, contenant une fraction 1-hydroxyphényle portant en position 3 un substituant aminocarboxy, la position 5 et le substituant aminocarboxy en position 3 étant reliés par une chaîne aliphatique à longueur variable. Selon l'invention, un dérivé de la position 1-hydroxy du cycle phénylique est obtenu avec un groupe aminoalkylèneaminocarbonyle, le groupe alkylène (qui peut être éventuellement substitué par des groupes alkyle) présentant une longueur de chaîne de 2 ou 3 atomes de carbone, un acide phosphorique ou un groupe ester d'acide phosphorique (p. ex. un ester alkylique) ou un sel associé et le groupe de dérivation augmentant l'hydrosolubilité et/ou la biodisponibilité de la molécule parent. De tels composés sont utiles en thérapie, p. ex., dans le traitement du cancer et de malignités de cellules B.

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