MANNOSYL-1 PHOSPHATE, ZUBEREITUNGSVERFAHREN UND THERAPEUTISCHE VERWENDUNG, IM BESONDEREN GEGEN DAS CDG-IA-SYNDROM

摘要

Drug composition comprises an excipient and an active ingredient (T) e.g. mono (alpha -D-mannopyranosyl-1) phosphates, in a medium. Drug composition comprises an excipient and an active ingredient (T) e.g. mono (alpha -D-mannopyranosyl-1) phosphate of formula (I), (II) and/or (III), in a medium. R 11-R 14, R 21-R 24H or OH protecting group (preferably 2-6C aliphatic acyl); R, R1a : T 1, OB 1, O-CH(CH 3)-O-CO-(1-5C)alkyl, -O-CH(CH 3)-O-CO-O-(1-5C)alkyl or -O-CH 2-CH(OH)-CH 2OH, preferably OB 1, phenoxy, 1-naphtyloxy, benzyloxy, 1-naphtylmethoxy, -O-CH(Q)-O-CO-O-(1-5C) alkyl, -O-CH 2-CH(OH)-CH 2OH, OH protecting group, -NH-(CH 2) 4-CH(NH 2)COOH, -(p-O)-C 6H 4-CH 2-CH(NH 2)COOH, -O-CH 2-CH(NH 2)COOH or -O-CH(CH 3)- CH(NH 2)COOH, -NH-(CH 2) 3-CH-(NH 2)COOH or -NH-(CH 2) 2-CH(NH 2)COOH (where COOH and NH 2of each group is protected); T 16-10C aryloxy, (6-10C)aryl(1-5C)alkyleneoxy (both optionally substituted by T 2), -O-CH 2-CH(OH)-CH 2OH, OH protecting group (2-6C acyl), -X-A-CH(COOY 1)(NZ 2Z 3)- or -(Z 2)N-CH(Z 4)-COOY 1; T 21-5C alkyl, 1-5C alkoxy, halo, CF 3and/or NO 2; B 1optionally branched 2-21C ethylenic unsaturated hydrocarbon chain or 5-21C cycloaliphatic group, preferably farnesyloxy or geranyloxy group; X : -O-, -S- or -NZ 1; Y 12-5C alkyl; A, Z 41-5C alkylene, phenylene or phenylalkylene group; Z 1-Z 3H, 1-5C alkyl, or N protecting group; R1 : OH protecting group (2-6C acyl), 1-20C alkoxy, -O-CH(Q)-O-CO-alkyl, -O-CH(Q)-O-CO-O-(1-5C)alkyl, OB 1or T 1, phenoxy, 1-naphtyloxy, benzyloxy, 1-naphtylmethoxy, -O-CH(Q)-O-CO-O-(1-5C) alkyl, -O-CH 2-CH(OH)-CH 2OH, OH protecting group, -NH-(CH 2) 4-CH(NH 2)COOH, -(p-O)-C 6H 4-CH 2-CH(NH 2)COOH, -O-CH 2-CH(NH 2)COOH or -O-CH(CH 3)- CH(NH 2)COOH, -NH-(CH 2) 3-CH-(NH 2)COOH or -NH-(CH 2) 2-CH(NH 2)COOH (where COOH and NH 2of each group is protected); Q : H or CH 3; and R 31-R 34H or OH protecting group (preferably 3-6C aliphatic acyl). Independent claims are included for: (1) a mannosyl-1 phosphate derivative of formula (I), (II) and/or (III) useful as a drug; and (2) a process of preparing (I), (II) and (III) comprising reaction of a 1-bromo-mannopyranose of formula (IVa) with a monosilver phosphate of formula AgOP(=O)(R)(R1a), reaction of a 1-bromo-mannopyranose of formula (IVb) with the monosilver phosphate to form (II) and reaction of a 1-bromo-mannopyranose of formula (IVc) with a trisilverphosphate of formula P(=O)(AgO) 3, respectively. [Image] [Image] ACTIVITY : Metabolic. MECHANISM OF ACTION : None given.