6-deoxy-sulfones cyclodextrin derivatives and preparation method thereof

A technology of deoxysulfones and cyclodextrins is applied in the field of preparing muscle relaxant antagonistic drugs, which can solve the problems of lack of specificity, limited clinical use, etc., so as to achieve the effect of reversing muscle relaxant effect, restoring neuromuscular conduction function, and ensuring life safety. Effect

Active Publication Date: 2009-12-02
HANGZHOU ADAMERCK PHARMLABS INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, this type of drug has no specificity and can act on all nerve endings, so it can cause a variety of serious adverse reactions, which limits its clinical use

Method used

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  • 6-deoxy-sulfones cyclodextrin derivatives and preparation method thereof
  • 6-deoxy-sulfones cyclodextrin derivatives and preparation method thereof
  • 6-deoxy-sulfones cyclodextrin derivatives and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] The synthesis of embodiment 1α-chloroacetylglycine

[0060]

[0061] Add 90g (1.2mol) of glycine to a 2000mL four-necked reaction flask, add about 400mL of water and stir to dissolve, and gradually add 64g (0.6mol) of finely ground anhydrous sodium carbonate. After adding and dissolving, cool in an ice-salt bath, add about 135.5 g (1.2 mol) of α-chloroacetyl chloride dropwise while vigorously stirring, and add sodium carbonate solution dropwise to keep the reaction solution weakly alkaline. After the addition, continue Stir for 4h, acidify to pH=1 with hydrochloric acid. Extracted twice with ethyl acetate, combined the extracts, added an appropriate amount of anhydrous sodium sulfate to dry overnight, filtered, and the filtrate was distilled under reduced pressure until crystals were precipitated, left overnight, filtered, and dried to obtain 123.6 g of colorless needle crystals, with a yield of about 68%.

Embodiment 2

[0062] Example 2 Synthesis of α-chlorophenylacetylglycine

[0063]

[0064] Add 90g (1.2mol) of glycine to a 2000mL four-necked reaction flask, add about 400mL of water and stir to dissolve, and gradually add 64g (0.6mol) of finely ground anhydrous sodium carbonate. After adding and dissolving, cool with an ice-salt bath, add about 226.85 g (1.2 mol) of α-chlorophenylacetyl chloride dropwise while vigorously stirring, and add sodium carbonate solution dropwise to keep the reaction solution weakly alkaline. Stirring was continued for 4h, acidified with hydrochloric acid to pH=1. Extracted twice with ethyl acetate, combined the extracts, added an appropriate amount of anhydrous sodium sulfate to dry overnight, filtered, and the filtrate was distilled under reduced pressure until crystals were precipitated, left overnight, filtered, and dried to obtain 180.3 colorless needle crystals, with a yield of about 66 %.

Embodiment 3

[0065] Embodiment 3 Preparation of potassium salt aqueous solution of thionicotinic acid

[0066]

[0067] (42g, 0.75mol) sodium hydrosulfide, 150ml water, stirred to dissolve. Nicotinyl chloride (49.54 g, 0.35 mol) was added dropwise under cooling in an ice bath, and the temperature was controlled not to exceed 15°C. After the dropwise addition, continue to stir for 1 hour, then cool to 0°C, add hydrochloric acid to neutralize, filter to obtain solid thionicotinic acid, then slowly add potassium carbonate water to dissolve, filter to obtain a yellow aqueous solution of thionicotinic acid potassium salt 60.6g, yield 97.7%.

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PUM

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Abstract

The invention provides 6-deoxy-sulfones cyclodextrin derivatives, which have a structure in a formula (I). The preparation method comprises the following steps: taking 6-deoxy-thioether aminoacid cyclodextrin derivatives or 6-deoxy-thioether cyclodextrin derivatives as raw materials, and obtaining 6-deoxy-sulfoxide cyclodextrin derivatives through oxidation reaction 1; and furthering oxidizing to obtain the 6-deoxy-sulfones cyclodextrin derivatives, wherein the 6-deoxy-thioether aminoacid cyclodextrin derivatives are prepared by the following steps: performing halogenation on acetic acid containing R3 substituent to obtain double halides; performing condensation on the double halides and amino acid to obtain acid amides; adding a sulfur reagent to obtain a sulfur-containing compound; removing protecting groups to obtain a sulfhydryl compound; and performing condensation on the sulfhydryl compound and halogenated cyclodextrin. The compounds provided by the invention can be used for reversing the phenomenon of neuromuscular relaxation induced by human or animal muscular relaxants, have effects of reversing and antagonizing the muscular relaxation induced by the muscular relaxants, and can be applied to the preparation of medicaments for antagonizing the muscular relaxation.

Description

technical field [0001] The invention belongs to the field of chemical industry and pharmacy, and relates to 6-deoxysulfone-like cyclodextrin derivatives and a preparation method thereof, mainly to 6-deoxysulfoxide-based cyclodextrin derivatives and 6-deoxysulfone-based cyclodextrin derivatives and their preparation The method, and the application in the preparation of muscle relaxation antagonistic drugs. technical background [0002] In 1980, Fujita.K. first reported the synthesis of monosubstituted 2-hydroxyethylthiocyclodextrin in Tetr.Lett. In 1993, Ling.C. and Darry.R. reported the synthesis of fully substituted 2-hydroxyethyl Thiocyclodextrin, its structural formula is: [0003] [0004] In 1986, Tubashi, I. reported the synthesis of o-carboxyphenylthiocyclodextrin in J.A.C.S.; in 1995, Guillo, F. reported the synthesis of carboxymethylthiocyclodextrin; in 1996, Baer, ​​H.H. and Santoyo-Gonzalez, F. Preparation of 2,3-dihydroxypropylthiocyclodextrin. Its structur...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08B37/16
CPCC08B37/0012A61K31/724A61P43/00
Inventor 漆又毛揭清张冯敏余葆春
Owner HANGZHOU ADAMERCK PHARMLABS INC
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