4-N-substituted sialic acids and their sialosides
AssigneeE. I. Du Pont de Nemours and Company
InventorSubramamiam Sabesan
Life of this patent
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Abstract
Novel azide groups containing sialosides and a process for their preparation is provided. The methods and resulting compounds may be of pharmaceutical interest for the inhibition of the influenza virus neuraminidase.
Claims7
A process for the hydrochlorination of 4-azido-2,3-dehydrosialic acids or 4-deoxy-2,3-dehydrosialic acids (I) to the corresponding 4-azido-2-chlorosialic acids or 4-deoxy-2-chlorosialic acids (II) according to the equation ##STR7## where R.sup.1 is C.sub.1 to C.sub.20 alkyl;
- R.sup.2 is azido or hydrogen;
- R.sup.3 is H or a C.sub.1 to C.sub.20 hydrocarbyl or substituted hydrocarbyl;
- and
- R.sup.4 is acyl containing from 1 to 8 carbon atoms, or a C.sub.1 to C.sub.20 alkyl;
- which process comprises contacting under substantially anhydrous conditions the 4-azido-2,3-dehydrosialic acid or 4-deoxy-2,3-dehydrosialic acid with anhydrous hydrogen chloride in the presence of a polar aprotic solvent or a organic carboxylic acid solvent.
A compound of the structure ##STR8## where X is oxygen, sulfur, CR.sup.9 R.sup.10, or NR.sup.11,
- R.sup.1 is H, C.sub.1 -C.sub.20 alkyl, a mono, di or polyvalent cation of an alkali metal, alkaline earth metal or transition metal, or an ammonium or substituted ammonium ion;
- R.sup.2 is azido, acylamino, where the acyl group contains from 1 to 8 carbon atoms, amino, hydrogen or guanidino;
- R.sup.3 is H or a C.sub.1 to C.sub.20 hydrocarbyl or substituted hydrocarbyl;
- R.sup.4 is H, acyl containing from 1 to 8 carbon carbon atoms, or a C.sub.1 to C.sub.20 alkyl;
- R.sup.5 is H, a C.sub.1 to C.sub.20 hydrocarbyl or substituted hydrocarbyl;
- R.sup.6 and R.sup.6 ' are H, OH, a C.sub.1 to C.sub.20 alkoxy or substituted alkoxy, a mono, di or oligosaccharide, or an alkylideneoxy taken together with R.sup.7 ' when R.sup.7 ' is not H;
- provided that one of R.sup.6 and R.sup.6 ' must be H but R.sup.6 and R.sup.6 ' may not both be H;
- and
- R.sup.7 and R.sup.7 ' are H, acyl containing from 1 to 8 carbon atoms, or a C.sub.1 to C.sub.20 alkyl, aryl, or alkylidene taken together with an adjacent R.sup.6, R.sup.6 ' R.sup.7 or R.sup.7 ';
- where R.sup.9, R.sup.10 and R.sup.11 are independently H or a C.sub.1 -C.sub.20 hydrocarbyl or substituted hydrocarbyl.
A compound of the structure ##STR9## where R.sup.1 is H, C.sub.1 -C.sub.20 alkyl, a mono, di or polyvalent cation of an alkali metal, alkaline earth metal or transition metal, or an ammonium or substituted ammonium ion;
- R.sup.2 is azido, acylamino, where the acyl group contains from 1 to 8 carbon atoms, amino, guanidino, or hydrogen;
- R.sup.3 is H or C.sub.1 to C.sub.20 hydrocarbyl or substituted hydrocarbyl;
- R.sup.4 is H, acyl containing from 1 to 8 carbon atoms or a C.sub.1 to C.sub.20 alkyl;
- R.sup.8 is C.sub.1 to C.sub.20 hydrocarbyl or substituted hydrocarbyl, acyl containing from 1 to 8 carbon atoms;
- R.sup.9, R.sup.10 and R.sup.11 are independently H or a C.sub.1 -C.sub.20 hydrocarbyl or substituted hydrocarbyl;
- and
- X is oxygen, sulfur, CR.sup.9 R.sup.10 or NR.sup.11.
A method for inhibiting sialidase activity comprising contacting sialidase with a compound of the formula III ##STR10## where X is oxygen, sulfur, CR.sub.9 R.sup.10, or NR.sub.11 ;
- R.sup.1 is H, a mono, di or polyvalent cation of an alkali metal, alkaline earth metal or transition metal, or an ammonium or substituted ammonium ion;
- R.sup.2 is amino or a guanidino;
- R.sup.3 is H or C.sub.1 to C.sub.20 hydrocarbyl or substituted hydrocarbyl;
- R.sup.4 is H;
- R.sup.5 is a H, C.sub.1 to C.sub.20 hydrocarbyl or substituted hydrocarbyl;
- R.sup.6 and R.sup.6 ' are H, OH, a C.sub.1 to C.sub.20 alkoxy or substituted alkoxy, a mono, di or oligosaccharide, or an alkylideneoxy taken together with R.sup.7 ' when R.sup.7 ' is not H;
- provided that one of R.sup.6 and R.sup.6 ' must be H but R.sup.6 and R.sup.6 ' may not both be H;
- and
- R.sup.7 and R.sup.7 ' are H or alkylidene taken together with an adjacent R.sup.6, R.sup.6 ', R.sup.7 or R.sub.7 ';
- where R.sup.9, R.sup.10 and R.sup.11 are independently H or a C.sub.1 -C.sub.20 hydrocarbyl or substituted hydrocarbyl.
Dependencies are inferred from the claim text.