6-deoxysulfone cyclodextrin derivative and its preparation method

A technology of deoxysulfone and cyclodextrin is applied in the field of preparing muscle relaxant antagonistic drugs, which can solve the problems of limited clinical use and lack of specificity, and achieves the recovery of neuromuscular conduction function, reversal of muscle relaxant effect, and guarantee of life safety. Effect

Active Publication Date: 2011-11-30
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-deoxysulfone cyclodextrin derivative and its preparation method
  • 6-deoxysulfone cyclodextrin derivative and its preparation method
  • 6-deoxysulfone cyclodextrin derivative and its preparation method

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] The synthesis of embodiment 2α-chlorophenylacetyl glycine

[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] The preparation of the potassium salt aqueous solution of embodiment 3 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

6-deoxidized sulfone cyclodextrin derivatives with structure of formula (I) are provided by the present invention, which are prepared by the steps of oxidation 1 by using 6-deoxidized thioether amino acid cyclodextrin derivative or 6-deoxidized thioether cyclodextrin derivative as raw material to obtain 6-deoxidized sulfoxide cyclodextrin derivative, further oxidizing the resultant to obtain 6-deoxidized sulfonyl cyclodextrin derivative. In which, the 6-deoxidized thioether amino acid cyclodextrin derivative is prepared by following procedure: using acetic acid containing R3 substituent group to obtain dihalide through halogenation, condensing with amino acid to obtain amide, adding sulfur reagent to obtain sulfur-containing compound, removing the protecting group to obtain sulfhydryl compound, and then condensing with halogenated cyclodextrin to obtain the product. The compound provided by the present invention can be used to antagonize muscle relaxation effect induced by muscle relaxant drugs in patients or animals, has reversal and antagonistic effect to muscle relaxation induced by muscle relaxant drugs, and can be used to prepare drugs which have antagonistic effect to muscle 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 Patents(China)
IPC IPC(8): C08B37/16
CPCA61K31/724C08B37/0012A61P43/00
Inventor 漆又毛揭清张冯敏余葆春
Owner HANGZHOU ADAMERCK PHARMLABS INC
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