Modulators of the complement system comprising bis-glucopyranosyl arylene sulfate derivatives
AssigneeAmerican Cyanamid Company
InventorsJoseph P. Joseph, Seymour Bernstein
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Abstract
Bis-(.beta.-D-glucopyranosyl-1-oxy)-arylene sulfate derivatives, the cation salts thereof, useful as modulators of the complement system, the intermediates thereof and the process for the preparation of such intermediates and end products.
Claims23
A compound selected from those of the formula:
- ##STR5## wherein X is --SO.sub.3 M and M is a nontoxic pharmaceutically acceptable cation salt, wherein the salt forming moiety is selected from the group consisting of alkali metal, alkaline earth metal, aluminum, ammonia and substituted ammonia selected from the group consisting of trialkylamine (C.sub.1 -C.sub.6), piperidine, pyrazine, alkanolamine (C.sub.2 -C.sub.6) and cycloalkylamine (C.sub.3 -C.sub.6);
- R.sub.1 is selected from the group consisting of CH.sub.2 OX, COOH and COONa;
- n is an integer 2 or 3;
- and B is an arylene selected from the group consisting of:
- ##STR6##
The compound according to claim 1, 1,3-bis-(.beta.-D-glucopyranosyl-1-oxy)-phenylene, octakis(H-sulfate), octatriethylamine salt, having the structure ##STR7## where M is N.sup.+ H(C.sub.2 H.sub.5).sub.3.
The compound according to claim 1, 1,3-bis-(.beta.-D-glucopyranosyl-1-oxy)-phenylene, octakis(H-sulfate), octasodium salt, having the structure ##STR8##
A compound selected from those of the formula:
- ##STR11## wherein Y is selected from the group consisting of H and COCH.sub.3 ;
- R.sub.1 is selected from the group consisting of CH.sub.2 OY, COOCH.sub.3 and COOH;
- n is an integer 2 or 3;
- and B is an arylene selected from the group consisting of:
- ##STR12##
A process for the preparation of compounds of the formula:
- ##STR17## wherein X is --SO.sub.3 M and M is a nontoxic pharmaceutically acceptable cation salt, wherein the salt forming moiety is selected from the group consisting of alkali metal, alkaline earth metal, aluminum, ammonia and substituted ammonia selected from the group consisting of trialkylamine (C.sub.1 -C.sub.6), piperidine, pyrazine, alkanolamine (C.sub.2 -C.sub.6) and cycloalkylamine (C.sub.3 -C.sub.6);
- R.sub.1 is selected from the group consisting of CH.sub.2 OX, COOH and COONa;
- n is an integer 2 or 3;
- and B is an arylene selected from the group consisting of:
- ##STR18## which comprises reacting an arylene di-trimethylsilylether and an appropriate acetyl sugar with boron trifluoride etherate in methylene chloride, at ambient temperature for 4-30 hours, giving a 1,3-bis-(.beta.-D-glucopyranosyl-1-oxy)-arylene polyacetate;
- purifying by high performance liquid chromatography and then reacting with metallic sodium in methanol for about one hour, giving a 1,3-bis-(.beta.-D-glucopyranosyl-1-oxy)-arylene derivative;
- reacting with a trialkylamine(C.sub.1 -C.sub.6) compound triethylamine-sulfur trioxide in N,N-dimethylacetamide at 50.degree.-75.degree. C. for 3-16 hours, under an inert atmosphere and extracting with acetone, giving a polykis(H-sulfate), polytriethylamine salt;
- then reacting with a cation-containing compound wherein the salt forming moiety is selected from the group consisting of alkali metal, alkaline earth metal, aluminum, ammonia or substituted ammonia selected from the group consisting of piperidine, pyrazine, alkanolamine (C.sub.2 -C.sub.6) and cycloalkylamine (C.sub.3 -C.sub.6), and precipitating in ethanol, giving the final product.
Dependencies are inferred from the claim text.