- Synthesis and biological activity of 2-aminoimidazole triazoles accessed by Suzuki-Miyaura cross-coupling
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A pilot library of 2-aminoimidazole triazoles (2-AITs) was synthesized and assayed against Acinetobacter baumannii and methicillin-resistant Staphylococus aureus (MRSA). Results from these studies show that these new derivatives have improved biofilm dispersal activities as well as antibacterial properties against A. baumannii. With MRSA biofilms they are found to possess biofilm inhibition capabilities at low micromolar concentrations.
- Reyes, Samuel,Huigens Iii, Robert W.,Su, Zhaoming,Simon, Michel L.,Melander, Christian
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- Preparation of large ring acetylenic lactones by iodo lactonisation
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Reaction of ω-ene-7-yne carboxylic acids with (biscollidine)iodine(I) hexafluorophosphate led to large ring acetylenic lactones. In the case of 5- or 6-yne carboxylic acids, iodo enol lactones were preferentially obtained.
- Rousseau, Gérard,Strzalko, Tekla,Roux, Marie-Claude
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- Synthesis of Optically Active Maresin 2 and Maresin 2 n-3 DPA
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Maresins are among the most potent antiinflammatory lipid metabolites. We report stereoselective syntheses of maresin 2 and maresin 2 n-3 DPA. The anti -diol was constructed through epoxide ring opening of an optically active β,γ-epoxy aldehyde, synthesized in situ by Swern oxidation of the corresponding alcohol. Finally, the target compounds were synthesized through a Sonogashira coupling of a C9-C22 iodide and methyl (Z)-oct-4-en-7-ynoate or methyl oct-7-ynoate, respectively.
- Ogawa, Narihito,Amano, Takahito,Kobayashi, Yuichi
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- Iron Catalysis for Room-Temperature Aerobic Oxidation of Alcohols to Carboxylic Acids
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Oxidation from alcohols to carboxylic acids, a class of essential chemicals in daily life, academic laboratories, and industry, is a fundamental reaction, usually using at least a stoichiometric amount of an expensive and toxic oxidant. Here, an efficient and practical sustainable oxidation technology of alcohols to carboxylic acids using pure O2 or even O2 in air as the oxidant has been developed: utilizing a catalytic amount each of Fe(NO3)3·9H2O/TEMPO/MCl, a series of carboxylic acids were obtained from alcohols (also aldehydes) in high yields at room temperature. A 55 g-scale reaction was demonstrated using air. As a synthetic application, the first total synthesis of a naturally occurring allene, i.e., phlomic acid, was accomplished.
- Jiang, Xingguo,Zhang, Jiasheng,Ma, Shengming
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- Identification of a novel NAMPT inhibitor by combinatorial click chemistry and chemical refinement
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The identification of compounds able to inhibit the NAD salvage pathway is experiencing a growing popularity as it has been proposed to be a novel target for antitumoral and anti-inflammatory drugs. In this manuscript, we used the copper-catalyzed [3+2] cycloaddition between azides and alkynes (click chemistry) to identify novel NAMPT inhibitors with a triazole-containing tail group. 720 compounds were synthesized in the first round, allowing the identification of 17 hit compounds. The second round of optimization brought about the discovery of compound 43 which displayed a cytotoxicity of 20 nM on neuroblastoma cancer cells and an inhibition of NAMPT of 114 nM.
- Theeramunkong,Galli,Grolla,Caldarelli,Travelli,Massarotti,Troiani,Alisi,Orsomando,Genazzani,Tron
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- Succinct synthesis of saturated hydroxy fatty acids and: In vitro evaluation of all hydroxylauric acids on FFA1, FFA4 and GPR84
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Saturated hydroxy fatty acids make up a class of underexplored lipids with potentially interesting biological activities. We report a succinct and general synthetic route to saturated hydroxy fatty acids hydroxylated at position 6 or higher, and exemplify this with the synthesis of hydroxylauric acids. All regioisomers of hydroxylauric acids were tested on free fatty acid receptors FFA1, FFA4 and GPR84. The results show that the introduction of a hydroxy group and its position have a high impact on receptor activity.
- Kaspersen, Mads Holmgaard,Jenkins, Laura,Dunlop, Julia,Milligan, Graeme,Ulven, Trond
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- In situ proteome profiling of C75, a covalent bioactive compound with potential anticancer activities
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A library of cell-permeable, minimally tagged C75 analogues was synthesized and used to uncover biological targets in human liver cancer cells. Known targets of C75, namely FASN and CPT1A, together with other unknown targets, including PDIA3, TFRC, and GAPDH, were thus identified.
- Cheng, Xiamin,Li, Lin,Uttamchandani, Mahesh,Yao, Shao Q.
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- Synthesis and Properties of Aromatic-Terminated Diacetylene Organogelators and Their Application to Photopatterning of Polydiacetylenes
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A series of simply structured diacetylene-diamide-based gelators (DAGs) with aromatic terminals were synthesized, and their gelation and subsequent photopolymerization abilities were analyzed. DAGs with an adequate spacer length (n) and tolyl terminals (DA-Tn) interacted with aromatic solvents, such as benzene and xylenes, at elevated temperatures. During the subsequent cooling process, the DAGs interacted with each other through CH-πinteractions at their terminal positions. They also formed one-dimensional hydrogen bonding arrays through secondary amides, leading to stable organogels. These gels polymerized into π-conjugated polydiacetylenes (PDAs) under ultraviolet irradiation. In the p-xylene gels of DA-Tn, the spacer length exerted characteristic odd-even effects on the photopolymerization rates over a certain range (n = 3-6), which can be explained by periodic changes in the uniformity of the molecular packing modes. When the gelling solvent was changed to cyclohexane, the gelation and photopolymerization abilities were greatly improved because the DA-Tn gel networks became highly crystallized and transparent to ultraviolet light (254 nm). The ultimate conversion to PDA from DA-T8/cyclohexane gels was 45.2 wt %. Applying photolithographic techniques to the DAG with excellent photopolymerizability in the film state, we successfully fabricated microscale photopatterns of PDA. We also established a convenient removal process (development process) of DA monomers in unexposed areas. The resulting PDA patterns were quite stable to ambient light stimuli.
- Aoki, Ken'Ichi,Horitsugu, Kousuke,Narazaki, Kenta,Seki, Atsushi,Takahashi, Daiki,Tamaoki, Nobuyuki
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p. 13160 - 13169
(2021/11/16)
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- NOVEL LYSOPHOSPHATIDIC ACID DERIVATIVE
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PROBLEM TO BE SOLVED: To provide a compound that specifically activates an LPA4 receptor, and a pharmaceutical composition containing the same. SOLUTION: This invention relates to a novel lysophosphatidic acid derivative that has an agonistic action on an LPA4 receptor and is useful for the prevention and/or treatment of a disease with angiodysplasia caused by the LPA4 receptor, or a disease associated with angiopathy, or symptoms associated therewith. This invention also relates to a pharmaceutical composition containing the lysophosphatidic acid derivative. SELECTED DRAWING: None COPYRIGHT: (C)2021,JPOandINPIT
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Paragraph 0579-0581
(2021/05/28)
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- INSULIN CONJUGATES
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The present invention relates to a conjugate comprising a sulfonamide of formula (I) and an active pharmaceutical ingredient such as an insulin analog comprising at least one mutation relative to the parent insulin, wherein the insulin analog comprises a mutation at position B16 which is substituted with a hydrophobic amino acid and/or a mutation at position B25 which is substituted with a hydrophobic amino acid. The present invention further relates to a sulfonamide of formula (A). Moreover, the present invention relates to an insulin analog comprising at least one mutation relative to the parent insulin.
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Paragraph 0580; 0588-0590; 0591
(2020/07/05)
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- Preparation method of target BTK protein degradation compound, and application of compound in treating autoimmune diseases and tumors
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The invention provides a compound, the compound is a compound represented by a formula I, and a stereoisomer, geometric isomer, tautomer, nitrogen oxide, hydrate, solvate, metabolite, pharmaceuticallyacceptable salt and prodrug of the compound represented by the formula I. The compound has a strong degradation effect on wild-type BTK, has no inhibition or degradation effects on other targets suchas EGFR, ITK, TEC, and the like, and has an effect of specific targeted degradation of BTK proteins. The formula I is X-Y-Z.
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Paragraph 0240-0242
(2020/02/14)
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- Applications of targeted BTK degradation compound in treatment of autoimmune system diseases
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The invention discloses application of a targeted BTK degradation compound in treatment of autoimmune system diseases and in preparation of medicines which are used for treating or preventing autoimmune diseases. The targeted BTK degradation compound is a compound shown as formula I or a stereoisomer, a geometrical isomer, a tautomer, a nitric oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, and the targeted BTK degradation compound has good treatment and prevention effects on the autoimmune diseases. X-Y-Z is as shown in formula I which is disclosed in the specification.
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Paragraph 0234-0236
(2020/03/12)
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- Method for preparing acid through oxidating alcohols or aldehydes by oxygen
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The invention provides a method for preparing acid through oxidating alcohols or aldehydes by using oxygen or oxygen in air as an oxidant. The method comprises the steps: oxidating the alcohols or aldehydes to produce the acid at room temperature in an organic solvent in a manner of taking ferric nitrate (Fe(NO3)3.9H2O), 2,2,6,6-tetramethylpiperidyl nitrogen oxide (TEMPO) and an inorganic halide as catalysts and taking the oxygen or air as an oxidant, and oxidating diols to produce lactone; or, carrying out a reaction on the aldehydes, which serve as a raw material, under neutral conditions by taking ferric nitrate as a catalyst, and oxidating the aldehydes to produce the acid and peroxy acid. The method has the advantages that the method is environmentally friendly, the cost is low, the yield is high, the atomic economical efficiency is high, the compatibility of substrate functional groups is good, the reaction conditions are mild, a reaction scale can be enlarged, and the like, so that the method is suitable for being applied to industrial production.
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Paragraph 0163; 0164; 0165
(2017/09/29)
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- Bola type ribavirin compound, and preparation method and application thereof
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The invention relates to a Bola type ribavirin compound. A structure is shown as a general formula I. Through studying the characteristics of the special structure of the Bola type amphiphilic molecules, the structure optimization is performed by aiming at 1, 2, 4-ribavirin; the water solubility and the cancer cell growth inhibition rate of the compound are improved. Further, the compound has the capability of forming nanometer scale particles through self assembly in a water solution, so that the compound can be more easily gathered into the tumor tissues to realize the targeted medication through high permeability of the solid tumor and the retention effect. Meanwhile, as a nanometer medicine carrier, the compound can also encapsulate and seal other micromolecular medicine to reach the combined medication effect. In the general formula, n, R1, R2, R3 and R4 are defined as the patent claim. The formula I is shown as the accompanying drawing.
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Paragraph 0046; 0047; 0048; 0049
(2017/07/21)
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- BIMESOGENIC COMPOUNDS AND MESOGENIC MEDIA
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The invention relates to bimesogenic compounds of formula I wherein R11, R12, MG11, MG12, X11, X12 and Sp1 have the meaning given in claim 1, to the use of bimesogenic compounds of formula I in liquid crystal media and particular to flexoelectric liquid crystal devices comprising a liquid crystal medium according to the present invention.
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Paragraph 0274-0276
(2017/12/15)
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- COMPOUNDS FOR TREATING DISORDERS ASSOCIATED WITH BK CHANNEL MODULATION
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The present invention relates to a compound of formula I, or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein: Z is OR16 or NR17R18; R16 is H or alkyl; R17 is H or alkyl; R
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Page/Page column 71
(2016/09/22)
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- Methods and compositions for protein labeling using lipoic acid ligases
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The present disclosure provides compositions and methods of use thereof for labeling peptide and proteins in vitro or in vivo. The methods described herein employ lipoic acid ligase or mutants thereof, and lipoic acid analogs (e.g., lipoic acid analogs comprising a resorufin moiety) recognized by lipoic acid ligase and lipoic acid ligase mutants. Also provided herein is a method of imaging protein-protein interaction via a reaction mediated by lipoic acid ligase.
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Page/Page column 35; 36
(2016/04/05)
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- Development of an acid ceramidase activity-based probe
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Acid ceramidase is responsible for the ultimate step in the catabolism of (glyco)sphingolipids by hydrolysis of ceramide into sphingosine and free fatty acid. Deficiency in acid ceramidase is the molecular basis of Farber disease. Here we report the synthesis and characterization of an activity-based acid ceramidase probe.
- Ouairy, Cécile M. J.,Ferraz, Maria J.,Boot, Rolf G.,Baggelaar, Marc P.,Van Der Stelt, Mario,Appelman, Monique,Van Der Marel, Gijsbert A.,Florea, Bogdan I.,Aerts, Johannes M. F. G.,Overkleeft, Herman S.
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supporting information
p. 6161 - 6163
(2015/04/14)
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- BENZAMIDE DERIVATIVES USEFUL IN THE TREATMENT OF MUSCULAR DISORDERSAND PAIN AND FOR CONTROLLING SPASTICITY AND TREMORS
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The present invention relates to a compound of formula I, or a pharmaceutically acceptable salt thereof : (I) wherein: n is 0 or 1; R1 is selected from H, alkyl and aralkyl, wherein said alkyl and aralkyl groups may be optionally substituted by one or mor
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Page/Page column 58-59
(2015/06/18)
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- N-Substituted 2-aminoimidazole inhibitors of MRSA biofilm formation accessed through direct 1,3-bis(tert-butoxycarbonyl)guanidine cyclization
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Antibiotic resistance is a significant problem and is compounded by the ability of many pathogenic bacteria to form biofilms. A library of N-substituted derivatives of a previously reported 2-aminoimidazole/triazole (2-AIT) biofilm modulator was constructed via α-bromoketone cyclization with 1,3-bis(tert-butoxycarbonyl)guanidine, followed by selective substitution. Several compounds exhibited the ability to inhibit biofilm formation by three strong biofilm forming strains of methicillin resistant Staphylococcus aureus (MRSA). Additionally, a number of members of this library exhibited synergistic activity with oxacillin against planktonic MRSA. Compounds with this type of dual activity have the potential to be used as adjuvants with conventional antibiotics. The Royal Society of Chemistry.
- Yeagley, Andrew A.,Su, Zhaoming,McCullough, Kára D.,Worthington, Roberta J.,Melander, Christian
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p. 130 - 137
(2013/02/22)
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- Alkyne-tag Raman imaging for visualization of mobile small molecules in live cells
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Alkyne has a unique Raman band that does not overlap with Raman scattering from any endogenous molecule in live cells. Here, we show that alkyne-tag Raman imaging (ATRI) is a promising approach for visualizing nonimmobilized small molecules in live cells. An examination of structure-Raman shift/intensity relationships revealed that alkynes conjugated to an aromatic ring and/or to a second alkyne (conjugated diynes) have strong Raman signals in the cellular silent region and can be excellent tags. Using these design guidelines, we synthesized and imaged a series of alkyne-tagged coenzyme Q (CoQ) analogues in live cells. Cellular concentrations of diyne-tagged CoQ analogues could be semiquantitatively estimated. Finally, simultaneous imaging of two small molecules, 5-ethynyl-2′-deoxyuridine (EdU) and a CoQ analogue, with distinct Raman tags was demonstrated.
- Yamakoshi, Hiroyuki,Dodo, Kosuke,Palonpon, Almar,Ando, Jun,Fujita, Katsumasa,Kawata, Satoshi,Sodeoka, Mikiko
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supporting information
p. 20681 - 20689
(2013/02/23)
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- Modulating the development of E. coli biofilms with 2-aminoimidazoles
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The synthesis of a 20 member 2-aminoimidazole/triazole pilot library is reported. Each member of the library was screened for its ability to inhibit or promote biofilm development of either Escherichia coli and Acinetobacter baumannii. From this screen, E. coli-selective 2-aminoimidazoles were discovered, with the best inhibitor inhibiting biofilm development with an IC50 of 13 μM. The most potent promoter of E. coli biofilm formation promoted biofilm development by 321% at 400 μM.
- Reed, Catherine S.,Huigens III, Robert W.,Rogers, Steven A.,Melander, Christian
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scheme or table
p. 6310 - 6312
(2010/11/18)
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- Cat-ELCCA: A robust method to monitor the fatty acid acyltransferase activity of ghrelin O-acyltransferase (GOAT)
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Assays armed with catalytic signal amplification have arisen as superior systems for ultrasensitive detection of analytes. A conceptually new enzyme assay called cat-ELCCA (catalytic assay using enzyme-linked click-chemistry) is described, in which an enzyme-linked azide is utilized to arm the assay with catalytic fluorescence signal amplification. By using this assay technology, the first high-throughput screen for recently disclosed ghrelin O-acyltransferase (GOAT) was developed. Copyright
- Garner, Amanda L.,Janda, Kim D.
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supporting information; experimental part
p. 9630 - 9634
(2011/03/16)
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- Synthesis and Nuclear Magnetic Resonance Studies on a Series of Synthesis Long-chain Tellurophene Fatty Esters
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The synthesis and the results of the 1H and 13C NMR spectroscopic analyses of thirteen 2,5-disubstituted tellurophene fatty esters, containing substituents of different chain lengths, and of a monosubstituted tellurophene ester are repported.The tellurophene esters are obtained by cyclization of the corresponding conjugated intermediates with Na2Te in the presence of AgOAc in methanol.The tellurophene moiety in the alkyl chain induces a deshielding effect on the protons of the adjacent methylene prtons.The shift parameters of the tellurophene moiety on the shifts of the adjacent methylene carbon atoms are also determined.
- Jie, Marcel S. F. Lie Ken,Chau, Sherman H.
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p. 2642 - 2657
(2007/10/03)
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- Pesticidal compounds
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The present invention provides a class of novel substituted bicyclooctanes which have pesticidal activity, particularly against arthropod pests. Pesticidal formulations containing the compounds of the formula (I), their use in the control of pests and methods for their preparation are also disclosed.
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- DIELS-ALDER REACTIVITY OF PYRANOINDOL-3-ONES. PART 3. INTRAMOLECULAR DIELS-ALDER REACTIONS.
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Heating the 1-alkynylpyranoindol-3-ones (5), prepared from the alkynoic acids (3), results in intramolecular Diels-Alder reaction involving the indole-2,3-quinodimethane diene with subsequent extrusion of carbon dioxide to give the cycloalkacarbazoles (6).The pyranoindolones need not be isolated, since the 2-acylindol-3-ylacetic acids (8) undergo cyclodehydration and intramolecular Diels-Alder reaction when heated in an acidic anhydride as solvent.In contrast to the intramolecular Diels-Alder reaction involving the acetylenic compound (5a), the olefin (9) was a much poorer substrate.
- Moody, Christopher J.,Shah, Pritom,Knowles, Philip
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p. 3249 - 3254
(2007/10/02)
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- A GENERAL METHOD FOR THE SYNTHESIS OF DIACETYLENIC ACIDS
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A simple and convenient method for the synthesis of twelve novel alkadiynoic acids, HOOC(CH2)mCC-C-CC(CH2)n-CH3, is reported.
- Singh, Alok,Schnur, Joel M.
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p. 847 - 852
(2007/10/02)
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- Acides gras marques en position ω par un nucleide radioactif emetteur γ
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The synthesis of many saturated, acetylenic, olefinic (Z or E) fatty acids labeled with 123I or 131I at the ω-position has been achieved.The radioactive iodine atom is introduced by a I-, *I- exchange reaction; the influence on the yield of several parameters - presence of iodine carrier, fatty acid and water concentrations, solution acidity - has been studied.Experimental conditions which produce labeling yields higher than 95percent have been defined; these results have lead to a very easy labeling method used in several hospitals in the external study of myocardial metabolism of fatty acids.
- Riche, Francoise,Mathieu, Jean-Paul,Vincens, Maurice,Bardy, Andre,Comet, Michel,Vidal, Michel
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