1561-55-3Relevant academic research and scientific papers
IONIZABLE LIPIDS FOR NUCLEIC ACID DELIVERY
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Paragraph 00407, (2021/01/22)
The present document describes compounds, or pharmaceutically acceptable salt thereof, of a core formula (I) where R1 features an amine group, particularly useful in the formulation of lipid particles including nucleic acid therapeutic agents, or proteins, or both, and for delivery of nucleic acid and protein therapeutics to cells in vivo or ex vivo, including anticancer and vaccine applications.
New chemoenzymatic synthesis of (±)-n-(2-hydroxyethyl)-n,n-dime thyl- 2,3-bis(tetradecyloxy)-1-propanammonium bromide (dmrie)
Rustoy, Eduardo M,Dana, Alejandro
, p. 71 - 75 (2015/12/31)
Background: Cytofectins are a class of positively charged lipid molecules that can facilitate the functional entry of polynucleotides, macromolecules, and small molecules into living cells, escaping lysosomal degradation. One of the most potent cytofectins, dimyristoyl Rosenthal inhibitor ether (DMRIE), is presently being used to deliver differents active molecules into animal and human diseased tissues. To our knowledge, two synthetic routes for the preparation of DMRIE have so far been reported. One of them is based on the reaction of epichlorhydrin with either dimethylamine chloride or dimethylamine using an alkaline solution as solvent. The main disadvantage of these routes is the formation of 3-(N,N-diamino)-1,2-propanediol. In summary, the synthetic routes mentioned use epichlorohydrin or glycidol as starting materials, both of which have been described as carcinogenic agents. Additionally, sometimes the reaction conditions are drastic. An alternative route for the preparation of other cytofectins is the use of glycerol as the starting material. Glycerol is a non-carcinogenic compound, but its use as starting material results in an increased number of steps of this reaction, generating an increase in the total time of synthesis and the formation of a greater amount of waste and scrap. Based on the above, here we propose a new chemoenzymatic synthetic strategy using glycerol as a starting material. Methods: Initially, glycerol and vinyl benzoate were mixed in presence of Mucor miehei lipase (Lipozyme), it is converted into corresponding mono-benzoate (±)-1. Finally, DMRIE was obtained by the reaction of bromide (±)-3 with 2- dimethylaminoethanol (DMAE). Results: We studied the stability of compound (±)-1 under the working conditions applied in the preparation of intermediate alcohol (±)-2. Additionally, we study different experimental parameters. Conclusion: In summary, a new chemoenzymatic synthetic route was developed for the DMRIE using glycerol as the starting material. We studied and optimized various experimental parameters of the various synthetic steps, and reached to develop the methodology to multigram scale, which compared to processes reported so far, has the advantages of fewer synthetic steps, the use of less aggressive reagents environment and generating fewer waste allowed to obtain the desired product; which results in a viable method for synthesizing analogs to DMRIE.
New chemoenzymatic synthesis of (±)-n-(2-hydroxyethyl)-n,n-dime thyl-2,3-bis(tetradecyloxy)-1-propanammonium bromide (DMRIE)
Rustoy, Eduardo M.,Dana, Alejandro
, p. 71 - 75 (2016/01/15)
Background: Cytofectins are a class of positively charged lipid molecules that can facilitate the functional entry of polynucleotides, macromolecules, and small molecules into living cells, escaping lysosomal degradation. One of the most potent cytofectins, dimyristoyl Rosenthal inhibitor ether (DMRIE), is presently being used to deliver differents active molecules into animal and human diseased tissues. To our knowledge, two synthetic routes for the preparation of DMRIE have so far been reported. One of them is based on the reaction of epichlorhydrin with either dimethylamine chloride or dimethylamine using an alkaline solution as solvent. The main disadvantage of these routes is the formation of 3-(N,N-diamino)-1,2-propanediol. In summary, the synthetic routes mentioned use epichlorohydrin or glycidol as starting materials, both of which have been described as carcinogenic agents. Additionally, sometimes the reaction conditions are drastic. An alternative route for the preparation of other cytofectins is the use of glycerol as the starting material. Glycerol is a non-carcinogenic compound, but its use as starting material results in an increased number of steps of this reaction, generating an increase in the total time of synthesis and the formation of a greater amount of waste and scrap. Based on the above, here we propose a new chemoenzymatic synthetic strategy using glycerol as a starting material. Methods: Initially, glycerol and vinyl benzoate were mixed in presence of Mucor miehei lipase (Lipozyme), it is converted into corresponding mono-benzoate (±)-1. Finally, DMRIE was obtained by the reaction of bromide (±)-3 with 2-dimethylaminoethanol (DMAE). Results: We studied the stability of compound (±)-1 under the working conditions applied in the preparation of intermediate alcohol (±)-2. Additionally, we study different experimental parameters. Conclusion: In summary, a new chemoenzymatic synthetic route was developed for the DMRIE using glycerol as the starting material. We studied and optimized various experimental parameters of the various synthetic steps, and reached to develop the methodology to multigram scale, which compared to processes reported so far, has the advantages of fewer synthetic steps, the use of less aggressive reagents environment and generating fewer waste allowed to obtain the desired product; which results in a viable method for synthesizing analogs to DMRIE.
Lipid encapsulated interfering RNA
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Paragraph 0223; 0224, (2015/11/16)
The present invention provides compositions and methods for silencing gene expression by delivering nucleic acid-lipid particles comprising a siRNA molecule to a cell.
LIPIDOSOME PREPARATION, PREPARATION METHOD AND APPLICATION THEREOF
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Paragraph 0059; 0061, (2015/12/20)
The present invention discloses a liposome formulation, its preparation method, and its application in the treatment of diseases caused by abnormal gene expression. The liposome formulation comprises complementary cationic lipid pairs, phospholipids, and long-circulating lipids. The method of preparing the liposome formulation comprises: mixing the complementary cationic lipid pairs with the phospholipid and the long-circulating lipid to generate pre-formed vesicles; and then mixing the pre-formed vesicles with the nucleic acid solution to generate the liposome-nucleic acid formulation. This liposome formulation provided by the present invention is easily prepared; and in the treatment of diseases caused by abnormal gene expression, the liposome formulation can be used to deliver in vivo therapeutic agents, including nucleic acids.
Synthesis of lipid-oligonucleotide conjugates for RNA interference studies
Grijalvo, Santiago,Ocampo, Sandra M.,Perales, Jose C.,Eritja, Ramon
experimental part, p. 287 - 299 (2011/10/03)
The synthesis of RNA molecules carrying lipids at their 3′-termini and 5′-termini is reported. These conjugates were fully characterized by MALDI-TOF mass spectrometry and HPLC chromatography. The ability of these conjugates to silence gene expression was
SNALP FORMULATIONS CONTAINING POLYOXAZOLINE-DIALKYLOXYPROPYL CONJUGATES
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, (2012/01/13)
The present invention provides polyoxaline-dialkyloxypropyl conjugates (POZ-DAA), SNALP compositions comprising POZ-DAA conjugates and methods of using such SNALP compositions to introduce a therapeutic agent, such as a nucleic acid, into a cell (e.g., for the treatment of a disease or disorder).
LIPID ENCAPSULATED INTERFERING RNA
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Page/Page column 83, (2008/06/13)
The present invention provides lipid-based formulations for delivering, e.g., introducing, nucleic acid-lipid particles comprising an interfering RNA molecule to a cell, and methods of making, delivering, and administering such lipid-based formulations.
Novel cationic amphiphiles
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Page/Page column 64, 24, (2010/02/06)
A cationic amphiphile for facilitating transport of a biologically active molecule into a cell has the structure A-F-D, in which A is a lipid anchor, D is a head group, and F is a spacer group having the structure described herein. A method for facilitating transport of a biologically active molecule into a cell comprises preparing a lipid mixture comprising a cationic amphiphile having structure A-F-D, preparing a lipoplex by contacting the lipid mixture with a biologically active molecule; and contacting the lipoplex with a cell, thereby facilitating transport of the biologically active molecule into the cell.
Synthesis and transfection properties of novel non-toxic monocationic lipids. Variation of lipid anchor, spacer and head group structure
Fichert, Thomas,Regelin, Anne,Massing, Ulrich
, p. 787 - 791 (2007/10/03)
This report describes the synthesis and the transfection properties of novel monocationic non-toxic lipids. We have carried out structural variations in all three units of the transfection lipid, the lipid anchor, the spacer moiety and the positively charged head group. Our results lead to the conclusion that systematic modification of structural subunits is a promising way to enhance the transfection efficiency. (C) 2000 Elsevier Science Ltd. All rights reserved.
