Derivatives of basic polyene macrolides and their preparation
AssigneesLaboratoires Mayoly Spindler, Michel Seman
InventorsMichel Seman, Jean F. Nicolay
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Abstract
The present invention relates to basic polyene macrolide derivatives, characterized in that they comprise a basic polyene macrolide which is N-substituted by a 1-amino-1-deoxyketose group which in turn is substituted or unsubstituted, to a process for their preparation and to their use for obtaining drugs.
Claims11
A basic polyene macrolide compound of the formula (I) ##STR17## in which:
- R.sub.1 denotes the macrocylic part of amphotericin B and
- R.sub.2 represents a member selected from the group consisting of:
- (1) a structure of the formula:
- ##STR18## in which R.sup.3 is selected from the group consisting of a hydrogen atom and a methyl group, and R.sup.4 is selected from the group consisting of a hydrogen atom, a methyl, trichloromethyl, tert.-butyl, propyl, benzyl, phenyl group and a phenyl group substituted by a group selected from the group consisting of a methoxy, nitro and phosphate group,
- (2) - a structure of the formula:
- ##STR19## in which R.sup.5 and R.sup.6 are methyl groups, (3) - a structure of the formula:
- ##STR20## in which R.sup.7 is selected from the group consisting of a carboxyl, amide, nitrile and trihalogenomethyl group, and R.sup.8 is selected from the group consisting of a hydroxyl group, an amino group and a mercapto group,
- (4) - a structure of the formula:
- ##STR21## and a salt thereof, wherein said basic polyene macrolide compound is more soluble than the unsubstituted macrolide where R.sub.2 in formula I is hydrogen.
The Bronsted acid salt of a compound of claim 2.
A compound which is 1-amino-1-deoxy-D-arabinoglucuronyl-amphotericin B of the formula:
- ##STR22## or its N-methylglucosamide salt, or its mixed oxalate and ammonium salt, where R.sub.1 is the macrocyclic part of amphotericin B.
A compound which is 1-amino-1-deoxy-D-arabinoglucuroamidyl-amphotericin B of the formula:
- ##STR23## or its N-methylglucosamine salt, or its mixed oxalate and ammonium salt, where R.sub.1 is the macrocyclic part of amphotericin B.
A compound which is 1-deoxy-1-amino-4,6-O-benzylidene-D-fructosyl-amphotericin B of the formula:
- ##STR24## or its N-methylglucosamine salt, or its mixed oxalate and ammonium salt, wherein R.sub.1 is the macrocyclic part of amphotericin B.
A compound of the formula:
- ##STR25## in which:
- R.sub.1 denotes the macrocyclic part of amphotericin B and
- R.sub.2 represents a 1-amino-1-deoxyketose group substituted by substitutent(s) selected from the group consisting of (1) a divalent group of the formula ##STR26## replacing hydrogens of two different hydroxyl groups of the ketose, where R.sup.3 is selected from the group consisting of a hydrogen atom and a methyl group, and R.sup.4 is selected from the group consisting of a hydrogen, methyl, trichloromethyl, tert-butyl, propyl, benzyl, phenyl and phenyl substituted by a group selected from the group consisting of a methoxy, nitro and phosphate group, and (2) a monovalent group selected from the group consisting of methoxy, carboxyl, amide, nitrile, trihalogenomethyl, amine and mercapto group replacing a hydroxyl group of the ketose.
The N-methylglucosamine salt of 1-deoxy-1-amino-4,6-O-benzylidene-D-fructosyl-amphotericin B of the formula:
- ##STR27## where R.sub.1 is the macrocylic portion of amphotericin B.
The mixed oxalate-ammonium salt of 1-deoxy-1-amino-4,6-O-benzylidene-D-fructosyl amphotericin B of the formula:
- ##STR28## where R.sub.1 is the macrocyclic part of amphotericin B.
Dependencies are inferred from the claim text.