87327-03-5Relevant articles and documents
Compounds that bind to the interferon-gamma, preparation method thereof and medicaments containing same
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Page/Page column 21, (2008/06/13)
Compound capable of binding to gamma-interferon (γ-IFN), chosen from the molecules corresponding to formula (I) below: in which X is a divalent spacer group that is sufficiently long to allow the two oligosaccharide fragments A and B to each bind to one of the peptide sequences 125 to 143 of the C-terminal ends of a γ-interferon (γ-IFN) homodimer, n represents an integer from 0 to 10, and for example equal to 0, 1, 2, 3, 4 or 5, and each R independently represents a hydrogen atom, an SO3? group or a phosphate group, on the condition that no SO3? group is in the 3-position of the glucosamine units of compound (I). The invention also relates to the process for preparing these compounds, to the complexes formed by these compounds and gamma-interferon, and to the medicaments comprising these compounds or complexes.
SYNTHESIS OF HEPARIN FRAGMENTS. A CHEMICAL SYNTHESIS OF THE TRISACCHARIDE O-(2-DEOXY-2-SULFAMIDO-3,6-DI-O-SULFO-α-D-GLUCOPYRANOSYL)-(1->4)-O-(2-O-SULFO-α-L-IDOPYRANOSYL-URONIC ACID)-(1->4)-2-DEOXY-2-SULFAMIDO-6-O-SULFO-D-GLUCOPYRANOSE HEPTASODIUM SALT
Jacquinet, Jean-Claude,Petitou, Maurice,Duchaussoy, Philippe,Lederman, Isidore,Choay, Jean,et al.
, p. 221 - 242 (2007/10/02)
Known 3-O-benzyl-1,2-O-isopropylidene-α-D-glucofuranose was first converted into methyl 3-O-benzyl-1,2-O-isopropylidene-β-L-idofuranuronate.Acid hydrolysis, followed by acetylation and treatment with titanium tetrabromide, gave methyl (2,4-di-O-acetyl-3-O-benzyl-α-L-idopyranosyl bromide)uronate, which was immediately transformed into methyl 4-O-acetyl-3-O-benzyl-β-L-idopyranuronate 1,2-(tert-butyl orthoacetate).A two-step replacement of the 4-O-acetyl by a 4-O-chloroacetyl group gave the key derivative, crystalline methyl 3-O-benzyl-4-O-chloroacetyl-β-L-idopyranuronate 1,2-(tert-butyl orthoacetate).Condensation of this orthoester with an excess of crystalline benzyl 6-O-acetyl-3-O-benzyl-2-(benzyloxycarbonyl)amino-2-deoxy-α-D-glucopyranoside in chlorobenzene in the presence of 2,6-dimethylpyridinium perchlorate gave crystalline benzyl 6-O-acetyl-3-O-benzyl-2-(benzyloxycarbonyl)amino-2-deoxy-4-O-(methyl 2-O-acetyl-3-O-benzyl-4-O-chloroacetyl-α-L-idopyranosyluronate)-α-D-glucopyranoside in 40 percent yield.O-Demonochloroacetylation, followed by condensation with known 3,6-di-O-acetyl-2-azido-4-O-benzyl-2-deoxy-α-D-glucopyranosyl bromide in dichloromethane in the presence of 2,4,6-trimethylpyridine, silver triflate, and molecular sieve provided benzyl O-(3,6-di-O-acetyl-2-azido-4-O-benzyl-2-deoxy-α-D-glucopyranosyl)-(1->4)-O-(methyl 2-O-acetyl-3-O-benzyl-α-L-idopyranosyluronate)-(1->4)-6-O-acetyl-3-O-benzyl-2-(benzyloxycarbonyl)amino-2-deoxy-α-D-glucopyranoside in 88 percent yield.O-Deacetylation with sodium hydroxide, followed successively by O-sulfation in N,N-dimethylformamide in the presence of sulfur trioxide-trimethylamine complex, catalytic hydrogenolysis, and N-sulfation in water with the same sulfating agent, gave the heptasodium salt of O-(2-deoxy-2-sulfamido-3,6-di-O-sulfo-α-D-glucopyranosyl)-(1->4)-O-(2-O-sulfo-α-L-idopyranosyluronic acid)-(1->4)-2-deoxy-2-sulfamido-6-O-sulfo-D-glucopyranose.This trisaccharide, which is a fragment of the minimal antithrombin III-binding region in heparin, neither binds to antithrombin III nor induces anti-Xa activity.
