Derivatives of polyene macrolide antibiotics containing an...

C - Chemistry – Metallurgy – 07 – H

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260/230.35

C07H 17/08 (2006.01)

Patent

CA 1132542

Abstract Derivatives of polyene macrolide antibiotics containing an amino sugar moiety, process for the preparation there- of, and pharmaceutical compositions containing them. Disclosed are novel derivatives of polyene macrolide antibiotics of the general formula Image (I) wherein M is a polyene macrolide antibiotic moiety containing an amino sugar moiety, the amino group of which is substituted by X, wherein X is (II), Image (III), -R5 or hydrogen, wherein A and B independently of each other are hydrogen or NR3R4 or one of A and B is hydrogen and the other is -NH-?-R-NR3R4, R5 is an .alpha.-amino-acyl group; n is 1 to 3, t is zero or 1, and when t is zero p is zero to 4 and when t is 1 p is zero; z is zero or 1, and Y is hydrogen, alkyl, allyl, propargyl, benzyl or - 2 - phenylpropargyl, with the proviso that, when X is hydrogen, z must be 1 and Y allyl, propargyl, benzyl or phenylpropargyl; and the pharmaceutically acceptable acid addition salts thereof. The novel compounds may be prepared by methods known per se. Preferably the compounds are prepared by reaction of respective polyene macrolide antibiotic with a reactive derivative of a compound HOX' wherein the amino group(s) is(are) protected. The compounds wherein X is hydrogen and Y is allyl, propargyl, benzyl or phenylpropargyl can be prepared by reaction of the respective N-protected polyene macrolide antibiotic with a reactive derivative of propene, propyne, phenylpropyne or toluene. The compounds show antifungal activity and are useful in the treatment of fungal infections.

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