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US 6,284,736 B1Granted
Amphotericin derivatives
AssigneeBeecham Group Limited
InventorWilliam Skinner Maclachlan
Life of this patent
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Abstract
A compound of formula (I), or a pharmaceutically acceptable salt thereof: wherein R1 is a carboxylic acid group, a derivative thereof, a ketone residue, an aldehyde function or optionally substituted methyl; R2 is hydroxy, C1-8 alkoxy or a fluorine atom; and R3 is an amino group or a derivative thereof.
Claims11
A compound of formula (I), or a pharmaceutically acceptable salt thereof:
- wherein R1 is a carboxylic acid group, an ester thereof selected from the group consisting of alkoxycarbonyl, alkenyloxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, aralkyloxycarbonyl, and heteroaralkyloxycarbonyl, or a primary amide thereof, or —CHO, wherein any alkyl, alkenyl, or alkoxy group independently contains from one to six carbon atoms, wherein any aryl group is selected from the group consisting of phenyl and naphthyl either being unsubstituted or mono-, di-, or tri-substituted by a substituent selected from the group consisting of carboxy, C1-6 alkoxycarbonyl, hydroxy-C1-6 alkyl, C1-6 alkoxy, halogen, and an amino optionally substituted by C1-6 alkyl, and wherein any heteroaryl group is a 5- or 6-membered monocyclic or a 9- or 10-membered bicyclic group containing one or two heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;
- R2 is hydroxy, C1-8 alkoxy or a fluorine atom;
- and R3 is an amino group.
A compound selected from the group consisting of 13-dehydroxy-13-fluoro-14-(S)-hydroxyamphotericin B methyl ester,
- 14-(S)-hydroxyamphotericin B methyl ester,
- 14-(S)-hydroxy-13-O-methylamphotericin B methyl ester,
- 14-(R)-hydroxy-13-O-methylamphotericin B methyl ester,
- 14-(R)-hydroxyamphotericin B, allyl ester,
- 14-(R)-hydroxyamphotericin B,
- 14-(S)-hydroxyamphotericin B methyl ester-(L)-Aspartate,
- 14-(R)-hydroxyamphotericin B methyl ester and
- 16-decarboxy-16-hydroxymethyl-14-(R)-hydroxy-amphotericin B.
5 more elements
An intermediate compound selected from the group consisting of:
- N-(9-fluorenylmethoxycarbonyl)-13-O-(3-chlorobenzoyl)-14-(S)-hydroxy-3,5,8,9,11,15,35,2′,4′-nona-O-triethyl-silylamphotericin B methyl ester,
- N-(9-fluorenylmethoxycarbonyl)-13-O-(3-chlorobenzoyl)-14-(S)-hydroxy-3,5,8,9,11,15,35,2′,4′-nona-O-trimethyl-silyl amphotericin B methyl ester and
- N-(9-fluorenylmethoxycarbonyl)-13-O-(3-chlorobenzoyl)-14-(S)-hydroxy amphotericin B methyl ester.
Dependencies are inferred from the claim text.