- LIPID NANOPARTICLE COMPOSITION
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Provided herein are lipids that can be used in combination with other lipid components, such as neutral lipids, cholesterol and polymer conjugated lipids, to form lipid nanoparticles for delivery of therapeutic agents (e.g., nucleic acid molecules) for therapeutic or prophylactic purposes, including vaccination.
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Paragraph 00422
(2021/10/15)
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- Neem PROTAC compound with STAT3 degradation activity and preparation method and application thereof
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A NEEM PROTAC compound with STAT3 degradation activity, the structure of which is generally formula (I): Y is a specific protein ligand in the E3 ubiquitin ligase complex, a Cereblon protein ligand or A VHL protein ligand; X is a linking group between nee
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Paragraph 0045; 0097-0099
(2022/01/10)
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- MOLECULES THAT STIMULATE THE IMMUNE SYSTEM FOR TREATMENT OF DRUG ADDICTION, METHODS OF SYNTHESIS, ANTIDRUG VACCINE AND USES
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This technology relates to immune system stimulating molecules to be used in the treatment of drug addiction and abuse and their synthesis processes. These molecules have a calixarene chemical structure, preferably calix[4]arene and/or calix[8]arene, coupled to an hapten analogous to cocaine, preferably GNE and/or GNC. An anti-drug vaccine, specifically anti-cocaine, is also described using such molecules. The anti-drug vaccine can be also used to prevent fetal exposure to drugs in pregnant women who use drugs and do not wish or cannot stop their use during pregnancy.
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Paragraph 0033; 0143; 0168-0171
(2020/12/20)
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- Discovery of Highly Polar β-Homophenylalanine Derivatives as Nonsystemic Intestine-Targeted Dipeptidyl Peptidase IV Inhibitors
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Although intensively expressed within intestine, the precise roles of intestinal dipeptidyl peptidase IV (DPPIV) in numerous pathologies remain incompletely understood. Here, we first reported a nonsystemic intestine-targeted (NSIT) DPPIV inhibitor with β-homophenylalanine scaffold, compound 7, which selectively inhibited the intestinal rather than plasmatic DPPIV at an oral dosage as high as 30 mg/kg. We expect that compound 7 could serve as a qualified tissue-selective tool to determine undetected physiological or pathological roles of intestinal DPPIV.
- Huang, Fubao,Ning, Mengmeng,Wang, Kai,Liu, Jia,Guan, Wenbo,Leng, Ying,Shen, Jianhua
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supporting information
p. 10919 - 10925
(2019/12/25)
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- CATIONIC LIPID
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The present invention provides a cationic lipid which is able to be used for nucleic acid delivery to the cytoplasm. A cationic lipid according to the present invention is, for example, a compound represented by formula (1a) or a pharmaceutically acceptable salt thereof. (In formula (1a), each of L1 and L2 independently represent an alkylene group having 3-10 carbon atoms; each of R1 and R2 independently represent an alkyl group having 4-22 carbon atoms or an alkenyl group having 4-22 carbon atoms; X1 represents a single bond or -CO-O-; and ring P represents one of formulae (P-1) to (P-5).)(In formulae (P-1) to (P-5), R3 represents an alkyl group having 1-3 carbon atoms.)
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Paragraph 0148-0151
(2019/05/10)
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- Copper-Catalyzed Reductive Trifluoromethylation of Alkyl Iodides with Togni's Reagent
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This work illustrates a reductive cross-electrophile coupling protocol for trifluoromethylation of alkyl iodides under Cu-catalyzed/Ni-promoted reaction conditions. The use of diboron esters as the terminal reductant allows the effective generation of the alkyl-CF3 products with excellent functional group tolerance and broad substrate scope. A mechanism involving a reaction of alkyl-Cu with Togni's reagent was proposed.
- Chen, Yanchi,Ma, Guobin,Gong, Hegui
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supporting information
p. 4677 - 4680
(2018/08/07)
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- Manganese-Catalyzed Borylation of Unactivated Alkyl Chlorides
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The use of low-cost manganese(II) bromide (MnBr2) and tetramethylethylenediamine (TMEDA) catalyzes the cross coupling of (bis)pinacolatodiboron with a wide range of alkyl halides, demonstrating the first manganese-catalyzed coupling with alkyl electrophiles. This method allows access to primary, secondary, and tertiary boronic esters from the parent chlorides, which were previously inaccessible as coupling partners. The reaction proceeds in high yield with as little as 1000 ppm catalyst loading, while 5 mol % can provide high yields in as little as 30 min. Finally, radical-clock experiments revealed that at 0 °C direct borylation outcompetes alternative radical processes, thereby providing synthetically useful, temperature-controlled reaction outcomes.
- Atack, Thomas C.,Cook, Silas P.
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supporting information
p. 6139 - 6142
(2016/06/09)
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- O-Benzylation of Carboxylic Acids Using 2,4,6-Tris(benzyloxy)-1,3,5-triazine (TriBOT) under Acidic or Thermal Conditions
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Two methods for the synthesis of benzyl esters from carboxylic acids using the O-benzylating reagent 2,4,6-tris(benzyloxy)-1,3,5-triazine (TriBOT) have been developed. The reactions were conducted either in the presence of a catalytic amount of TfOH at room temperature (acidic conditions) or in the absence of TfOH at 180-230 C (thermal conditions). Interestingly, the O-benzylation of hydroxy carboxylic acids under the two conditions afforded different products: The dibenzylated product under acidic conditions and the hydroxy ester under thermal conditions. In addition to these results, other evidence indicated that the former reaction proceeds through an SN1-type mechanism, and the latter by an SN2-type mechanism. Two methods for the O-benzylation of carboxylic acids using TriBOT have been developed under either acidic or thermal conditions. The O-benzylation of hydroxy carboxylic acids afforded the dibenzylated product under acidic conditions and the hydroxy ester under thermal conditions. The former reaction proceeds through an SN1-type mechanism and the latter by an SN2-type mechanism.
- Yamada, Kohei,Yoshida, Saki,Fujita, Hikaru,Kitamura, Masanori,Kunishima, Munetaka
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p. 7997 - 8002
(2015/12/24)
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- Synthesis and evaluation of phenoxymethylbenzamide analogues as anti-trypanosomal agents
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The synthesis and anti-trypanosomal activity of a compound library based on a phenoxymethylbenzamide hit discovered in a high throughput screen is described. Several of the analogues exhibited potent activity against Trypanosoma brucei rhodesiense, a human infective strain of the trypanosome parasite, that serve as lead compounds for further optimisation. This journal is
- Manos-Turvey, Alexandra,Watson, Emma E.,Sykes, Melissa L.,Jones, Amy J.,Baell, Jonathan B.,Kaiser, Marcel,Avery, Vicky M.,Payne, Richard J.
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supporting information
p. 403 - 406
(2015/03/18)
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- COMPOUNDS
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The invention relates to new derivatives of 5-aminolevulinic acid (5-ALA) and their use as photosensitizing agents. In particular, it relates to compounds of general formula I and their pharmaceutically acceptable salts, to methods for preparing such compounds and their medical and cosmetic use, for example in methods of photodynamic therapy and diagnosis: wherein R1 represents a hydrogen atom or an optionally substituted alkyl or cycloalkyl group; R2, each of which may be the same or different, represents a hydrogen atom or an optionally substituted alkyl group; and X is a linking group.
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Page/Page column 49
(2014/02/16)
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- Liquid crystalline 4-(2,3 Dihydroxypropoxy) diphenyl 4-n-alcoxy acids
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4-(2,3 Dihydroxypropoxy) diphenyl 4-oxy-hexanoic acid and 4-(2,3 dihydroxypropoxy) diphenyl 4-oxy-undecanoic acid have been synthesized and analyzed by IR and NMR experiments. The liquid crystalline character and the phase transitions of these two acids have been studied by differential scanning calorimetry (DSC) and variable temperature X-ray diffraction (VTXRD). These two liquid crystalline monomers are designed to be flexible, rigid and polyfunctional, so that they can be used in the synthesis of new macromolecules with side chain liquid crystals.
- Lopez-Velazquez, Delia,Hernandez-Sosa, Armando R.,Perez, Ernesto,Castillo-Rojas, Susana
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experimental part
p. 175 - 184
(2012/04/05)
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- Halogenation of primary alcohols using a tetraethylammonium halide/[Et 2NSF2]BF4 combination
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The halogenation of primary alcohols is presented. The use of a combination of tetraethylammonium halide and [Et2NSF2]BF4 (XtalFluor-E) allows for chlorination and bromination reactions to proceed efficiently (up to 92% yield) with a wide range of alcohols. Iodination reactions are also possible albeit in lower yields.
- Pouliot, Marie-France,Mahe, Olivier,Hamel, Jean-Denys,Desroches, Justine,Paquin, Jean-Francois
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supporting information
p. 5428 - 5431,4
(2020/10/15)
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- Functionalized biodegradable triclosan monomers and oligomers for controlled release
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This invention relates to the discovery of functionalized triclosan monomers and oligomers that, when incorporated into a substrate of, or applied as part of a coating to, medical devices and/or consumer products may extend the duration of antimicrobial properties to the medical devices and/or consumer products.
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Page/Page column 64-65
(2011/11/13)
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- Oxidation of primary aliphatic and aromatic aldehydes with difluoro(aryl)-λ3-bromane
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Oxidation of primary aliphatic aldehydes with p- trifluoromethylphenyl(difluoro)-λ3-bromane in dichloromethane at 0 °C afforded acid fluorides selectively in good yields, while that of aromatic aldehydes in chloroform at room temperature produced aryl difluoromethyl ethers. A larger migratory aptitude of aryl groups compared to primary alkyl groups during a 1,2-shift from carbon to an electron-deficient oxygen atom in bromane(III) Criegee-type intermediates will result in these differences in the reaction courses.
- Ochiai, Masahito,Yoshimura, Akira,Hoque, Md. Mahbubul,Okubo, Takuji,Saito, Motomichi,Miyamoto, Kazunori
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p. 5568 - 5571
(2011/12/03)
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- FUNCTIONALIZED BIODEGRADABLE TRICLOSAN MONOMERS AND OLIGOMERS FOR CONTROLLED RELEASE
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This invention relates to the discovery of functionalized triclosan monomers and oligomers that, when incorporated into a substrate of, or applied as part of a coating to, medical devices and/or consumer products may extend the duration of antimicrobial properties to the medical devices and/or consumer products.
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- Solid-phase assembly and in situ screening of protein tyrosine phosphatase inhibitors
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(Chemical Equation Presented) A highly efficient solid-phase strategy for assembly of small molecule inhibitors against protein tyrosine phosphatase 1B (PTP1B) is described. The method is highlighted by its simplicity and product purity. A 70-member combinatorial library of analogues of a known PTP1B inhibitor has been synthesized, which upon direct in situ screening revealed a potent inhibitor (Ki = 7.0 μM) against PTP1B.
- Srinivasan, Rajavel,Lay, Pheng Tan,Wu, Hao,Yao, Shao Q.
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supporting information; experimental part
p. 2295 - 2298
(2009/05/11)
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- Tricycloundecane compounds useful as modulators of nuclear hormone receptor function
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Tricycloundecanes compounds, methods of using such compounds in the treatment of nuclear hormone receptor-associated conditions such as cancer and immune disorders, and pharmaceutical compositions containing such compounds are disclosed.
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Page/Page column 53
(2008/06/13)
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- Self-assembly of chiral depsipeptide dendrimers
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The self-assembly of chiral depsipeptide dendrons 4, which contain a cyanuric acid building block at their focal point, with the homotritopic Hamilton receptor 1 is reported. The 1:3 compositions of the resulting chiral supramolecular dendrimers, the association constants Kn, and the cooperativity of binding expressed by Scatchard plots and the Hill coefficients nH was determined by NMR titration experiments. The most pronounced positive cooperativity was found for the complexes 1L3 with L being the second-generation dendrons 4c-e. The least stable complexes are formed with the bulky third-generation dendrons 4f-h. Similar results are obtained by the corresponding complexation of the achiral Frechet-type first- to third-generation dendrons 3 with 1. Chiroptical investigations of 1:3 complexes of 1 and 4 reveal chirality transfer from the dendron to the Hamilton receptor as demonstrated by the appearance of new CD absorption bands at 310 nm.
- Hager, Kristine,Franz, Alexander,Hirsch, Andreas
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p. 2663 - 2679
(2008/02/03)
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- High-load, soluble oligomeric carbodiimide: Synthesis and application in coupling reactions
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A facile preparation of a high-load, soluble oligomeric alkyl cyclohexylcarbodiimide (OACC) reagent via ROM polymerization from commercially available starting materials is described. This reagent is exploited as a coupling reagent for esterification, amidation, and dehydration of carboxylic acids (aliphatic and aromatic) with an assortment of alcohols (aliphatic primary, secondary, and benzylic), thiols, phenols, and amines (aliphatic primary, secondary, benzylic, and aromatic/anilines), respectively. Following the coupling event, precipitation with an appropriate solvent (Et2O, MeOH, or EtOAc), followed by filtration through a SPE provides the products in good to excellent yield and purity.
- Zhang, Mianji,Vedantham, Punitha,Flynn, Daniel L.,Hanson, Paul R.
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p. 8340 - 8344
(2007/10/03)
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- Multifunctional molecular complexes for gene transfer to cells
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A multifunctional molecular complex for the transfer of a nucleic acid composition to a target cell is provided The complex is comprised of A) said nucleic acid composition and B) a transfer moiety comprising 1) one or more cationic polyamines bound to sa
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- O-Protected N-(2-Nitrophenylsulfonyl)hydroxylamines: Novel Reagents for the Synthesis of Hydroxamates
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Preparative methods for novel O-protected N-(2-nitrophenylsulfonyl)hydroxylamines (8a-e) are described. Their versatility as intermediates en route to polyhydroxamates is examplified by the synthesis of a non-amide DFO analog 22.
- Reddy, Poreddy Amruta,Schall, Otto F.,Wheatley, James R.,Rosik, Leonard O.,McClurg, Joseph P.,Marshall, Garland R.,Slomczynska, Urszula
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p. 1086 - 1092
(2007/10/03)
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- Esterification of carboxylic acids with boron trichloride
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Treatment of carboxylic acids with boron trichloride followed by addition of alcohol provides the carboxylic ester. This esterification, following BCl3 ether or ester O-C cleavage reaction conditions, proceeds cleanly in good yields with most substrates. Cleavage of benzyl esters with boron trichloride then treating with methanol affords the methyl ester.
- Dyke, Christopher A.,Bryson, Thomas A.
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p. 3959 - 3961
(2007/10/03)
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- Photoionization studies of chromophore-labeled amino acids and peptides
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The photoionization characteristics of a naphthol chromophore covalently tethered to a few different amino acids and small peptides are investigated. To isolate the chromophore from the biological molecules the linkage between them is constructed from saturated alkyl chains of up to 12 carbons in length. Experimental results are compared with those of previous studies that explored the photoionization of macromolecules.
- Houston, Christopher T.,Reilly, James P.
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p. 10383 - 10391
(2007/10/03)
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- Development of an Enzyme-Linked Immunosorbent Assay for the Detection of the Pyrethroid Insecticide Fenpropathrin
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A competitive enayme-linked immunosorbent assay (ELISA) was developed for the quantitative detection of fenpropathrin [(RS)-α-cyano-3-phenoxybenzyl-2,2,3,3-tetramethylcyclopropanecarboxylate]. Polyclonal antisera were isolated from rabbits immunized with two different fenpropathrin hapten conjugates. One hapten contained an amino function; the other contained a carboxyl group for conjugation to carrier proteins. Mollusk hemocyanins, thyroglobulin, and fetuin were used as carrier proteins. The antisera varied greatly in their affinities for fenpropathrin. A homologous assay system using the coating antigen format was the most sensitive. The IC50 for fenpropathrin was 20 μg/L, and the lower detection limit was 2.5 μg/L. Pyrethroids, such as phenothrin, permethrin, resmethrin, fenvalerate, deltamethrin, cyfluthrin, and cypermethrin, and the pyrethroid metabolites, 3-phenoxybenzoic acid and fenpropathrin acid, did not cross-react significantly in this assay. Ten percent acetone or methanol and a pH of 4 were determined to be optimum assay conditions. Various cationic, anionic, and nonionic detergents had no significant effect on the assay.
- Wengatz, Ingrid,Stoutamire, Donald W.,Gee, Shirley J.,Hammock, Bruce D.
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p. 2211 - 2221
(2007/10/03)
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- Substituted ethanolamine esters
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Compounds of the formula (I): Ar1 --CH(OH)--CH2 --NH--CH2 --X--CH2 --E--(CH2)n --Y--Ar2, in which the substituents and symbols have the meanings given in the description, are novel active compounds having, in particular, a broncholytic action.
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- Chelating agents
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A bifunctional chelating agent for joining an antibody or antibody fragment and a metallic radionuclide is disclosed. The agent consists of a derivative of 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid or a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, an organic linking radical which optionally contains a cleavable group, and a function capable of reacting with a site on a protein. Radiodiagnostic or radiotherapeutic precursors comprising an antibody or antibody fragment and the above-described bifunctional chelating agent and radiodiagnostic or radiotherapeutic agent comprising a metallic radionuclide and the above mentioned precursor are also disclosed.
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- Specificity of esterases and structure of prodrug esters: Reactivity of various acylated acetaminophen compounds and acetylaminobenzoated compounds
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The relative rates of enzymatically catalyzed hydrolysis of various esters of p-acetylaminobenzoic acid (APAB) and variously acylated acetaminophen (APAP) derivatives were measured. Neutral, anionic, and cationic esters were examined. The enzyme sources adopted were rat intestinal homogenate, rat liver homogenate, rat plasma, and a partly purified commercial enzyme. In both APAB and APAP esters, neutral esters were the most sensitive of the enzyme sources examined, and the sensitivity was due to the carbon chain length. The APAP esters were enzymatically more stable than the APAP esters. The relative rates of hydrolysis of these esters varied depending on the enzyme source. The ability of structure recognition was good in rat intestinal homogenate, but weak in rat plasma. These results suggest that ester prodrugs can be designed to cleave preferentially at selected sites along the pathway between absorption and disposition in the body.
- Seki,Kawaguchi,Higuchi
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p. 855 - 860
(2007/10/02)
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- Pyrido[2,1-b]quinazoline derivatives useful as agents for treatment of allergic conditions and vascular disorders involving thrombosis
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Pyrido[2,1-b]quinazoline derivatives of the formulas STR1 wherein R1, R2 and R3 are as hereinafter set forth, are described. The compounds of formulas I and II are useful as agents for the treatment of allergic conditions
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- Synthesis of Protected 2-Amino-8-oxo-9,10-epoxydecanoic Acid from 2-Aminosuberic Acid Derivatives
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A method is reported for synthesizing derivatives of 2-amino-8-oxo-9,10-epoxydecanoic acid (Aoe) from 2-aminosuberic acid (Asu) derivatives under conditions that do not disrupt peptide bonds.The epoxy ketone amino acid Aoe is found in three biologically active cyclic peptides.Ethyl 2-(acetylamino)suberate was converted to ethyl 2-DL-(acetylamino)-8-oxo-(RS)-9,10-epoxydecanoate in 45-50 percent yield by sequential reactions with phosphorus pentachloride followed by reaction with tetravinyltin and benzylchlorobis(triphenylphosphine)palladium(II) to give the vinyl ketone in 70 percent yield.Epoxidation of enone with tert-butyl hydroperoxide using triton B as catalyst gave the N-acetyl ethyl ester of Aoe in 70 percent yield.Methods for preparing protected 2-aminosuberic acid derivatives from glycine ester benzal imine are also described.
- Rich, Daniel H.,Singh, Jasbir,Gardner, Joseph H.
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p. 432 - 434
(2007/10/02)
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