Cationic lipid compound, composition containing same and application

A cationic lipid and compound technology, applied in the preparation of organic compounds, cyanide reaction preparation, medical preparations containing active ingredients, etc., can solve the problems of high sensitivity and low cell permeability, and achieve a variety of effects

Active Publication Date: 2021-06-18
SUZHOU ABOGEN BIOSCIENCES CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, nucleic acid therapeutics still face several challenges, including low cell permeability and high susceptibility to degradation of certain nucleic acid molecules, including RNA

Method used

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  • Cationic lipid compound, composition containing same and application
  • Cationic lipid compound, composition containing same and application
  • Cationic lipid compound, composition containing same and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0094] The synthetic route of compound 1 is as follows:

[0095]

[0096] Step 1: Synthesis of compound 1-1

[0097] To 2-hexyldecanol (2.0 g, 8.26 mmol, 1.0 eq) and 6-bromohexanoic acid (1.92 g, 10.0 mmol, 1.2 eq) in dichloromethane (30 mL) was added diisopropylethylamine ( 266.9mg, 2.08mmol, 0.25eq) and DMAP (201.8mg, 1.67mmol, 0.2eq). After the mixture was stirred at room temperature for 5 minutes, EDCI (2.85 g, 14.87 mmol, 1.8 eq) was added and the reaction mixture was stirred at room temperature overnight, then TLC showed complete disappearance of the starting alcohol. The reaction mixture was diluted with DCM (300 mL) and washed with saturated NaHCO 3 (100mL), water (100mL) and brine (100mL) for washing. The combined organic layers were washed with Na 2 SO 4 Drying and removal of the solvent in vacuo afforded the crude product, which was purified by column chromatography (silica gel column, eluent 0-1% EA (volume percent) in n-hexane) and the pure product fractio...

Embodiment 2

[0106] The synthetic route of compound 2:

[0107]

[0108] Step 1: Synthesis of Compound 2-1

[0109] A mixture of compound a (1.0 g, 4.7 mmol, 1.0 eq) and ethylamine in methanol (2M, 12 ml) was stirred at room temperature overnight. LCMS showed the reaction was complete. The reaction mixture was concentrated in vacuo, and the obtained residue was purified by column chromatography (silica gel column, eluent: PE: EA = 3: 1 (volume ratio), rotary evaporation to obtain compound 2-1 (238 mg, 19.7% yield rate). LCMS: Rt: 0.950 min; MS m / z (ESI): 258.3 [M+H] + .

[0110] Step 2: Synthesis of compound 2

[0111] Compound 2-1 (191.1 mg, 0.74 mmol, 1.0 eq), Compound 1-1 (620.8 mg, 1.47 mmol, 2.0 eq), K 2 CO 3 (306.3 mg, 2.22 mmol, 3.0 eq), Cs 2 CO 3 (71.7mg, 0.22mmol, 0.3eq) and a catalytic amount of NaI (32.9mg, 0.22mmol, 0.3eq) in acetonitrile (15ml) were stirred at 90°C overnight. LCMS showed the reaction was complete. The reacted mixture was diluted with EA and washe...

example 3

[0114] Example 3: Synthesis of Compound 3

[0115]

[0116] Step 1: Synthesis of compound 3-1

[0117] A mixture of compound a (500mg, 2.35mmol, 1.0eq) and propylamine (1.4g, 23.5mmol, 10.0eq) in ethanol (15ml) was stirred overnight at room temperature. LCMS showed the reaction was complete. The reaction mixture was concentrated in vacuo, and the obtained residue was purified by column chromatography (silica gel column, eluent: PE:EA=3:1 (volume ratio)), and rotary evaporated to obtain compound 3-1 (420mg, 66% Yield). LCMS: Rt: 1.125 min; MS m / z (ESI): 272.6 [M+H] + .

[0118] Step 2: Synthesis of compound 3

[0119] Compound 3-1 (201.7 mg, 0.74 mmol, 1.0 eq), Compound 1-1 (620 mg, 1.47 mmol, 2.0 eq), K 2 CO 3 (306.3 mg, 2.22 mmol, 3.0 eq), Cs 2 CO 3 (71.7mg, 0.33mmol, 0.3eq) and NaI (32.9mg, 0.22mmol, 0.3eq) in acetonitrile (15ml), stirred overnight at 90°C. LCMS showed the reaction was complete. The reacted mixture was diluted with EA and washed with water and ...

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Abstract

The invention provides a cationic lipid compound, a composition containing the cationic lipid compound and application of the cationic lipid compound. In order to provide more choices for delivery of preparations such as nucleic acid drugs, gene vaccines, small molecule drugs and the like, the invention provides a cationic lipid compound shown in the general formula or pharmaceutically available salts thereof. The cationic lipid compound provided by the invention can be used for delivering DNA, RNA or small molecule drugs, enriches the types of cationic lipid compounds, and has important significance for the development and application of nucleic acid preventive and therapeutic agents.

Description

technical field [0001] The present invention specifically relates to a cationic lipid compound, its composition and application. Background technique [0002] Therapeutic nucleic acids have the potential to revolutionize vaccination, gene therapy, protein replacement therapy, and other genetic disease treatments. Since the first clinical studies of therapeutic nucleic acids began in the 2000s, research into the design of nucleic acid molecules and their delivery methods has made significant progress. However, nucleic acid therapeutics still face several challenges, including low cell permeability and high susceptibility to degradation of certain nucleic acid molecules, including RNA. Therefore, it is necessary to develop more lipid compounds capable of delivering therapeutic or preventive agents, especially for the delivery of nucleic acid therapeutic agents, and related methods and compositions, so as to facilitate the extracellular or intracellular delivery of various the...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C229/12C07C229/14C07C227/08A61K9/51A61K31/7088A61K39/00A61K45/00A61K47/18
CPCA61K9/5123A61K31/7088A61K39/00A61K45/00A61K47/18C07C229/12C07C229/14C07C2601/02C07C2601/04C07C2601/08C07C2601/14
Inventor 英博王秀莲
Owner SUZHOU ABOGEN BIOSCIENCES CO LTD
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