- Process method for preparing polyol nicotinate compound
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The invention relates to a process method for preparing a polyol nicotinic acid ester compound. The process comprises the following steps of: (1) dispersing nicotinic acid in an aprotic solvent, adding carbonyl diimidazole until the solution is clear, and stirring to react until no bubble emerges to obtain an intermediate reaction solution; (2) adding a polyol reagent into the intermediate reaction solution, stirring, heating, carrying out reflux reaction, and separating, washing and drying an obtained reaction product to obtain a polyol nicotinate compound crude product; and (3) dissolving the polyol nicotinate ester compound crude product in deionized water in a suspension manner, dropwise adding a nitric acid aqueous solution, dissolving solids until the solution is clear, decolorizing, filtering, neutralizing, separating out a large amount of solids, filtering, and drying to obtain a target product, namely, the nicotinate ester compound. According to the method, pyridine with high toxicity and heavy odor is not used as a reaction solvent, the problem of air pollution caused by sulfur dioxide generated by using thionyl chloride is also avoided, and the whole process is simple and convenient to operate, high in yield, high in purity and the like.
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Paragraph 0053-0070
(2021/10/13)
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- Orally active heparin salts containing multivalent cationic units
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The invention provides novel orally active salts of the formula STR1 in which is the skeleton of a polyol, n is the number of OH's in the polyol (3 to 24); p is ≥3 and ≤n; r is the available valence of the heparin unit and ≥3 and ≤7; sr is equal to pv; and R+ is STR2 in which Riv is C1 -C3 alkyl; R' and R" are C1 -C7 alkyl, the same or different, or combined so that --NR'R" represents the residue of a saturated monocyclic secondary amine; R"' is identical to the corresponding portion of a natural amino acid; the alkylene groups contain 1 to 3 carbon atoms; and Rv is H, --CONH2 or --COO(C1 -C7 alkyl). The salts are stable lipoidal "ion pairs" or complexes which can be absorbed through the gastrointestional wall and which slowly release heparinic acid to achieve long-lasting anticoagulant activity. Novel quaternary salts which are intermediates to the heparin salts of the invention are also disclosed.
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