- In silico design and pharmacological evaluation of conjugates of atenolol with modified saccharide for cardiovascular targeting
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Amongst a wide range of biological macromolecules, saccharides exhibit the potential to be specifically recognized by cell-surface receptors and hence can be utilized as ligands in targeted drug delivery. The current study aims to use saccharides viz. Galactose, Pectin and Chitosan to improve targeting of Atenolol by oxalyl chloride mediated grafting. Conjugates were engineered by grafting Atenolol, a cardiovascular agent with the modified saccharide units. The conjugates were characterized by FTIR, DSC and 1H NMR study. Drug release analysis and cellular uptake study was carried out using H9c2 cell lines which represent that concentration of drug in cells treated with all atenolol-saccharide conjugates is enhanced by almost two-folds in comparison with cells treated with atenolol solution. Thus cell line study confers the evidence of selective cardiac delivery. No significant cytotoxicity was observed in case of all synthesized conjugates in the Brine shrimp lethality bioassay. Possible binding of the developed conjugates with the GLUT-4 receptors was assessed by in silico analysis using homology model developed by Swiss Model server. Hence it was concluded that the application of these conjugates with saccharides in selective cardiovascular drug delivery can be a promising approach to increase bioavailability, minimize drug loss by degradation and prevent harmful side effects by increasing specific cell targeting. Graphical abstract: [Figure not available: see fulltext.]
- Kumbhar, Smita Tukaram,Patil, Shitalkumar Shivgonda,Bhatia, Manish Sudesh
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Read Online
- Preparation method of [alpha]-oxo-2-furanacetic acid
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The invention belongs to the field of preparation of organic compounds, and particularly relates to a preparation method of [alpha]-oxo-2-furanacetic acid, which comprises the following steps: 1) preparing oxalic acid and an organic alkali solution, controlling the temperature to 5-10 DEG C, dropwisely adding a trichloromethyl carbonate solution into the oxalic acid and organic alkali solution, and keeping the temperature for 2-4 hours until the solid is completely dissolved to obtain a solution A; obtaining a first solution; 2) preparing a furan and Lewis acid solution, controlling the temperature to be 20-25 DEG C, then dropwise adding the first solution into the furan and Lewis acid solution, and carrying out heat preservation for 1-2 hours to obtain a second solution; and 3) quenching the second solution at 0-10 DEG C to obtain the [alpha]-oxo-2-furanacetic acid. The preparation method disclosed by the invention does not generate nitric oxide and composite salt, and is low in treatment difficulty, low in environmental harm, low in temperature required by the whole reaction, low in energy consumption, simple in reaction step and short in time consumption.
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Paragraph 0032-0033; 0042-0043; 0050-0051
(2021/05/01)
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- Citrate plasticizer and preparation method thereof
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The invention discloses a citrate plasticizer and a preparation method thereof. The preparation method comprises the following steps: firstly, carrying out reaction on citric acid and alcohol to prepare citric acid triester; acylating dianhydride to prepare carboxyl-containing triester citrate; carrying out acylating chlorination on the carboxyl-containing triester citrate, and then carrying out esterification reaction on the carboxyl-containing triester citrate and tri(2-hydroxyethyl) isocyanurate to prepare triester citrate containing isocyanurate; and finally, esterifying with fatty acyl chloride to obtain the modified citrate plasticizer. The preparation method is simple to operate, wide in raw material source and mild in reaction condition, and meets industrial production. The prepared triester citrate containing isocyanurate has a good plasticizing effect and excellent thermal stability, low-temperature flexibility, solvent extraction resistance, migration resistance and flame retardance, and can be widely applied to plastic rubber plasticizers.
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Paragraph 0054; 0057
(2021/05/29)
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- BIFUNCTIONAL CYTOTOXIC AGENTS
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Cytotoxic dimers comprising CBI-based and/or CPI-based sub-units, antibody drug conjugates comprising such dimers, and to methods for using the same to treat cancer and other conditions.
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Page/Page column
(2015/08/04)
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- Sensor Comprising Resrufin Levulinate Having Sulfite Ion Selectivity and Method for Monitoring Sulfite Ion Using the Same
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The present invention relates to a sensor comprising a resorufin compound having sulfite ion selectivity and a method for detecting sulfite ions using the same. More specifically, the resorufin compound may have outstandingly increased fluorescence intensity by a deprotection reaction that a levulinyl group is cleaved with a sulfite ion to be used as a selective fluorescence sensor of turn-on type, and also represent a chromogenic change to detect sulfite ions by naked eye.
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- Thienopyridine and furopyridine kinase inhibitors
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Compounds having the formula are useful for inhibiting protein tyrosine kinases. The present invention also discloses methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.
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- Isotopically coded affinity markers 3
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The invention concerns isotopically coded affinity markers (ICAT) for mass spectrometric analysis of proteins, and the preparation and use if said markers.
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- Inhibition of the complete set of mammalian secreted phospholipases A 2 by indole analogues: A structure-guided study
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Structure-guided design was employed in a search for potent and selective inhibitors of mammalian secreted phospholipases A2 (sPLA 2s). Using the X-ray structures of human groups IIA and X sPLA 2s (hGIIA and hGX) as templates, homology structural models were made for the other human and mouse sPLA2s (hGIB, mGIB, mGIIA, mGIIC, hGIID, mGIID, hGIIE, mGIIE, hGIIF, mGIIF, hGV, mGV, and mGX). Me-Indoxam is a previously discovered indole analogue that binds tightly to many sPLA 2s, and the X-ray structure of the hGX-Me-Indoxam complex was determined at a resolution of 2.0 A. Modeling suggests that the residues near the N1-substituent of Me-Indoxam vary significantly among the mammalian sPLA2s, and therefore a library of 83 N1- variants was prepared by parallel synthesis. Several Me-Indoxam analogues bearing a 4-(2-oxy-ethanoic acid) side chain were potent inhibitors (IC 50 5 μM) hGIID, mGIID, hGIIF, and mGIIF. Me-Indoxam analogues bearing a 5-(4-oxy-butanoic acid) side chain were generally less potent inhibitors. Although no compounds were found to be highly specific for a single human or mouse sPLA2, combinations of Me-Indoxam analogues were discovered that could be used to distinguish the action of various sPLA2s in cellular events. For example, Me-Indoxam and compound 5 are approximately 5-fold more potent on hGIIA than on hGV, and compound 21 is 10-fold more potent on hGV versus hGIIA.
- Smart, Brian P.,Pan, Ying H.,Weeks, Amanda K.,Bollinger, James G.,Bahnson, Brian J.,Gelb, Michael H.
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p. 1737 - 1749
(2007/10/03)
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- Taxol enhancer compounds
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One embodiment of the present invention is a compound represented by the Structural Formula (I): Y is a covalent bond of a substituted or unsubstituted straight chained hydrocarbyl group. In addition, Y, taken together with both >C=Z groups to which it is bonded, is a substituted or unsubstituted aromatic group. Preferably, Y is a covalent bond or —C(R7R8)—. R1 is an aliphatic group, a substituted aliphatic group, a non-aromatic hetereocyclic group, or a substituted non-aromatic hetereocyclic group, R2-R4 are independently —H, an aliphatic group, a substituted aliphatic group, a non-aromatic hetereocyclic group, a substituted non-aromatic hetereocyclic group, an aryl group or a substituted aryl group, or R1 and R3 taken together with the carbon and nitrogen atoms to which they are bonded, and/or R2 and R4 taken together with the carbon and nitrogen atoms to which they are bonded, form a non-aromatic heterocyclic ring optionally fused to an aromatic ring. R5-R6 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group. R7 and R8 are each independently —H, an aliphatic or substituted aliphatic group, or R7 is —H and R8 is a substituted or unsubstituted aryl group, or, R7 and R8, taken together, are a C2-C6 substituted or unsubstituted alkylene group. Z is ═O or ═S. Also disclosed are pharmaceutical compositions comprising the compound of the present invention and a pharmaceutically acceptable carrier or diluent.
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- Indole derivatives as anti-inflammatory agents
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This invention relates to compounds, which are generally anti-inflammatory and analgesic compounds, and which are represented by Formula I: wherein A is a —CH2—, —O—, —S—, or —S(O)—; and the other substituents are as defined in the specification; or individual isomers, mixtures of isomers, and pharmaceutically acceptable salts thereof. The invention further relates to pharmaceutical compositions containing such compounds and methods for their use as therapeutic agents
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- Compounds useful as reversible inhibitors of cysteine proteases
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Disclosed are novel cathepsin S, K, F, L and B reversible inhibitory compounds of the formulas (I), (II), (Ia) and (Ib) further defined herein. The compounds are useful for treating autoimmune diseases. Also disclosed are processes for making such novel compounds.
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- Chemical compounds
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The invention relates to quinazoline derivatives of the formula: [wherein: Y1represents —O—, —S—, —CH2—, —SO—, —SO2—, —NR5CO—, —CONR6—, —SO2NR7—, —NR8SO2— or —NR9— (wherein R5, R6, R8and R9each independently represents hydrogen, alkyl or alkoxyalkyl); R1represents hydrogen, hydroxy, halogeno, nitro, trifluoromethyl, cyano, alkyl, alkoxy, alkylthio, amino or alkylamino. R2represents hydrogen, hydroxy, halogeno, alkyl, alkoxy, trifluoromethyl, cyano, amino or nitro; m is an integer from 1 to 5; R3represents hydroxy, halogeno, alkyl, alkoxy, alkanoyloxy, trifluoromethyl, cyano, amino or nitro; R4represents a group which is or which contains an optionally substituted pyridone, phenyl or aromatic heterocyclic group] and salts thereof; processes for their preparation and pharmaceutical compositions containing a compound of formula I or a pharmaceutically acceptable salt thereof as active ingredient. The compounds of formula I and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.
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- N-acyl cyclic amine derivatives
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The invention relates to compounds represented by the general formula [I][wherein Ar means an aryl group or a heteroaryl group which may have a substitutive group selected from a group consisting of a halogen atom, a lower alkyl group and a lower alkoxy group; R1 means a C3-C6 cycloalkyl group which is substitutable with a fluorine atom; R2 and R4 mean hydrogen atoms, groups represented by -(A1)m-NH-B or the like; R3 and R5 mean hydrogen atoms, C1-C6 aliphatic hydrocarbon groups or the like which are substitutable with a lower alkyl group(s); n means 0 or 1; and X means an oxygen atom or a sulfur atom]. Compounds according to the invention, since they not only have potent selective antagonistic activity against muscarinic M3 receptors but also exhibit excellent oral activity, durability of action and pharmacokinetics, are very useful as safe and effective remedies against respiratory, urinary and digestive diseases with little adverse side effects.
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- Antineoplastic heteronapthoquinones
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This invention relates to a naphthoquinone derivatives, to processes and to intermediates for preparing these derivatives, to pharmaceutical composition and to the use of these derivatives as antitumor agents in mammals.
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- Processes antineoplastic heteronaphthoquinones
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This invention relates to a naphthoquinone derivatives, to processes and to intermediates for preparing these derivatives, to pharmaceutical composition and to the use of these derivatives as antitumor agents in mammals.
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- Multiple Bonds between Atoms of Main Group Elements and Transition Metals, CVIII. - Stoichiometric and Catalytic Oxidation of Electron-poor Olefins with Osmium Tetraoxide: A Novel Oxidation Method for Fluoroolefins
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In contrast to current opinion, osmium tetraoxide reacts even with very electron-poor olefins.For example, both partially and fully fluorinated osmate(VI) esters 2 are thus formed from fluoroolefins 1 by cycloaddition.Hydrolysis of the osmate(VI) esters leads to the corresponding 1,2-diols 3 and, eventually, consecutive fluoroorganic products by HF elimination.A catalytic version of this route opens a new, general, and efficient entry to oxidation products in fluoroolefin chemistry.Tetrahalide ethylene derivatives of formula split off oxalyl halide upon thermal treatment with the complexes py2O2OsX2 thus being formed in good yields. Key Words: Osmium tetraoxide, oxidation with / cis-Hydroxylation, catalytic / Fluoroolefins
- Herrmann, Wolfgang A.,Eder, Stefan J.
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- Perhalodioxins and Perhalodihydrodioxins
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Two perhalo-1,4-dihydrodioxins, representatives of a previously unknown class of compounds, have been synthesized and shown to exhibit unusual reactivity.In particular, reaction with oxygen is spontaneous and exothermic, and radical-catalyzed homopolymerization will proceed through a fluorinated double bond.Representatives of the perhalo-2,3-dihydro-1,4-dioxin class have also been prepared and found to have reactivity in general intermediate to that of the perhalodioxoles and acyclic trifluorovinyl ethers.Computational studies of the two systems established thatintroduction of the first double bond raises the energy substantially, while the second double bond results in a near-planar ring with dramatically increased energy content.
- Krespan, Carl G.,Dixon, David A.
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p. 3915 - 3923
(2007/10/02)
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- Process for the preparation of oxalyl chloride
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In a process for the preparation of oxalyl chloride from an oxalic acid compound of the formula STR1 wherein R1 and R2 are identical or different and represent hydrogen or a lower alkyl radical, and phosphorus pentachloride in the presence of phosphorus oxychloride, the improvement wherein the reaction is carried out in the presence of an amino compound of the formula STR2 wherein R3 represents alkyl, aralkyl, aryl or an acyl group, optionally substituted by amino or carboxamido and R4 and R5 are identical or different and represent hydrogen or alkyl, aralkyl, or aryl, optionally substituted by amino or carboxamido, or R4 and R5 are linked in an optionally substituted carbocyclic ring with 5 to 7 ring members, which optionally contains nitrogen, sulphur and/or oxygen and is optionally substituted by alkyl, aralkyl, aryl and/or amino groups, and R3 represents hydrogen or alkyl, which can be linked with R4 to form a carbocyclic ring, aralkyl or aryl, optionally substituted by an amino or carboxamido group, or optionally forms a double bond in one of the radials R4 or R5, and the oxalyl chloride formed is distilled off during the reaction.
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- Bis-2N-alkylene tetrahydroisoquinoline compounds
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Bis-2N-alkylene tetrahydroisoquinoline compounds are inhibitors of phenylethanolamine N-methyl-transferase.
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- Acylated derivatives of substituted piperazines and polymeric compositions stabilized thereby
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Acylated derivatives of substituted piperazines are stabilizers for synthetic polymeric materials normally subject to deterioration caused by ultraviolet light. The compounds are prepared by the acylation reaction between a substituted piperazine and a mono or di-acid halide, ester or isocyanate. Polymeric compositions containing these stabilizers may also contain a hindered phenolic compound. A typical embodiment is 15-stearoyl-7,15-diazadispiro[5,1,5,3]hexadecane.
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