- Selective catalytic oxidation of diglycerol
-
The selective oxidation of α,α-diglycerol was studied using oxygen as a clean oxidant in the presence of a palladium/neocuproine complex. After optimization of the reaction parameters, the mono-oxidation product was obtained with 93% NMR yield (up to 76% isolated yield). The product was named “diglycerose” considering that it mainly exists as a cyclic hemi-ketal form.
- Wang, Huan,Vu, Nam Duc,Chen, Guo-Rong,Métay, Estelle,Duguet, Nicolas,Lemaire, Marc
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supporting information
p. 1154 - 1159
(2021/02/26)
-
- Selective targeting of human and animal pathogens of the helicobacter genus by flavodoxin inhibitors: Efficacy, synergy, resistance and mechanistic studies
-
Antimicrobial resistant (AMR) bacteria constitute a global health concern. Helicobacter py-lori is a Gram‐negative bacterium that infects about half of the human population and is a major cause of peptic ulcer disease and gastric cancer. Increasing resistance to triple and quadruple H. pylori eradication therapies poses great challenges and urges the development of novel, ideally narrow spectrum, antimicrobials targeting H. pylori. Here, we describe the antimicrobial spectrum of a family of nitrobenzoxadiazol‐based antimicrobials initially discovered as inhibitors of flavodoxin: an essential H. pylori protein. Two groups of inhibitors are described. One group is formed by nar-row‐spectrum compounds, highly specific for H. pylori, but ineffective against enterohepatic Helico-bacter species and other Gram‐negative or Gram‐positive bacteria. The second group includes ex-tended‐spectrum antimicrobials additionally targeting Gram‐positive bacteria, the Gram‐negative Campylobacter jejuni, and most Helicobacter species, but not affecting other Gram‐negative pathogens. To identify the binding site of the inhibitors in the flavodoxin structure, several H. pylori‐flavodoxin variants have been engineered and tested using isothermal titration calorimetry. An initial study of the inhibitors capacity to generate resistances and of their synergism with antimicrobials commonly used in H. pylori eradication therapies is described. The narrow‐spectrum inhibitors, which are ex-pected to affect the microbiota less dramatically than current antimicrobial drugs, offer an oppor-tunity to develop new and specific H. pylori eradication combinations to deal with AMR in H. pylori. On the other hand, the extended‐spectrum inhibitors constitute a new family of promising antimi-crobials, with a potential use against AMR Gram‐positive bacterial pathogens.
- Aínsa, José A.,Anoz‐carbonell, Ernesto,Berlamont, Helena,Conde‐giménez, María,Díaz‐de‐villegas, María D.,Gálvez, José A.,Galano‐frutos, Juan José,Haesebrouck, Freddy,Mahía, Alejandro,Maity, Ritwik,Mamat, Uwe,Salillas, Sandra,Sancho, Javier,Schaible, Ulrich E.,Touati, Eliette,Velazquez‐campoy, Adrian
-
-
- Ammonium Chloride-Promoted Rapid Synthesis of Monosubstituted Ureas under Microwave Irradiation
-
Monosubstituted ureas are important scaffolds in organic chemistry. They appear in various biologically active compounds and serve as versatile precursors in synthesis. Monosubstituted ureas were originally prepared using toxic and hazardous phosgene equivalents. Modern methods include transamidation of urea and nucleophilic addition to cyanate salts, both of which suffer from a narrow substrate scope due to the need for a strong acid and prolonged reaction times. We hereby report that ammonium chloride can promote the reaction between amines and potassium cyanate to generate monosubstituted ureas in water. This method proceeds rapidly under microwave irradiation and tolerates a broad range of functional groups. Unlike previous strategies, it is compatible with other nucleophiles, acid-labile moieties, and most of the common protecting groups. The products precipitate out of solution, allowing facile isolation without column chromatography.
- Lan, Chunling Blue,Auclair, Karine
-
supporting information
p. 5135 - 5146
(2021/10/19)
-
- Gold(I)-catalyzed, one-pot, oxidative formation of 2,4-disubstituted thiazoles: Application to the synthesis of a pateamine-related macrodiolide
-
Thiazoles are important heterocyclic motifs in many target molecules. Extension of a reported gold(I)-catalyzed oxidative coupling of alkynes and thioamides to the synthesis of functionalized thiazole-containing products is presented, including the compatibility of this reaction with ester, protected hydroxyl, alkene and thioether groups. The utility of this one-pot process is demonstrated in the preparation of the thiazole-containing macrodiolide of a simplified analogue of pateamine A.
- Xu, Tao,Cuyamendous, Claire,Brown, Sarah L.,Andreassend, Sarah K.,Cumming, Hemi,Evans, Gary B.,Teesdale-Spittle, Paul H.,Harvey, Joanne E.
-
-
- Design and Synthesis of Tetrazole- And Pyridine-Containing Itraconazole Analogs as Potent Angiogenesis Inhibitors
-
Itraconazole, a widely used antifungal drug, was found to possess antiangiogenic activity and is currently undergoing multiple clinical trials for the treatment of different types of cancer. However, it suffers from extremely low solubility and strong interactions with many drugs through inhibition of CYP3A4, limiting its potential as a new antiangiogenic and anticancer drug. To address these issues, a series of analogs in which the phenyl group is replaced with pyridine or fluorine-substituted benzene was synthesized. Among them the pyridine- and tetrazole-containing compound 24 has significantly improved solubility and reduced CYP3A4 inhibition compared to itraconazole. Similar to itraconazole, compound 24 inhibited the AMPK/mTOR signaling axis and the glycosylation of VEGFR2. It also induced cholesterol accumulation in the endolysosome and demonstrated binding to the sterol-sensing domain of NPC1 in a simulation study. These results suggested that compound 24 may serve as an attractive candidate for the development of a new generation of antiangiogenic drug.
- Cheng, Zhiqiang,Head, Sarah A.,Li, Ruo-Jing,Li, Yingjun,Liu, Jun O.,Liu, Wukun,Pasunooti, Kalyan Kumar,Peng, Hanjing,Shi, Wei Q.
-
supporting information
p. 1111 - 1117
(2020/07/04)
-
- Synthesis of glycerol-derived 4-alkyl-substituted 1,2,3-triazoles and evaluation of their fungicidal, phytotoxic, and antiproliferative activities
-
Herein, the synthesis of nine novel glycerol-derived 4-alkyl-substituted 1,2,3-triazoles, using the CuI-catalyzed alkyne-azide cycloaddition reaction as the key step, is reported. The triazoles were characterized by infrared and nuclear magnetic resonance (NMR 1H and 13C) spectroscopy and mass spectrometry. The nine prepared compounds were evaluated with regard to their phytotoxic, antiproliferative, and fungicidal activities. The fungicidal activity was assessed on Colletotrichum gloeosporioides, the causative agent of papaya anthracnose. All compounds presented high efficiency (comparable to the commercial fungicide tebuconazole) in inhibiting C. gloeosporioides sporulation. The phytotoxicity of the triazoles was assessed against Lactuca sativa. Germination was the less-affected parameter, whereas the most pronounced effects of the triazoles were on the germination speed index and root growth of the L. sativa seedlings. As indicators of antiproliferative activity, the mitotic index was evaluated along with chromosomal and nuclear alterations, all of which were influenced to different degrees by the triazoles. In addition, all derivatives demonstrated aneugenic and clastogenic actions in meristematic cells of L. sativa roots. Therefore, these 4-alkyl-substituted triazoles may represent a scaffold to be explored for the development of new fungicidal agents.
- Costa, Adilson V.,Moreira, Luiza C.,Pinto, Roberta T.,Alves, Thammyres A.,Schwan, Vitor V.,de Queiroz, Vagner T.,Pra?a-Fontes, Milene M.,Teixeira, Róbson Ricardo,Morais, Pedro A.B.,de Jesus, Waldir C.
-
p. 821 - 832
(2020/04/27)
-
- NUCLEIC ACID OF FORMULA (I): GlXmGn, OR (II): ClXmCn, IN PARTICULAR AS AN IMMUNE-STIMULATING AGENT/ADJUVANT
-
The present invention relates to a nucleic acid of the general formula (I): GlXmGn, or (II): ClXmCn, which may be modified by a lipid. The nucleic acid of the invention acts as an immune-stimulating agent inducing the innate immune response. The invention relates further to a pharmaceutical composition (in a first embodiment), each containing an immune-stimulating agent according to the invention in combination with a pharmaceutically active carrier/vehicle (and, optionally, further auxiliary substances, additives and/or further adjuvants). In another embodiment, the inventive nucleic acid is combined with at least one pharmaceutically active component, a pharmaceutically acceptable carrier/vehicle (and, optionally, further auxiliary substances, additives and/or further adjuvants). Accordingly, the present invention is directed to a vaccine, which corresponds to a pharmaceutical composition of the invention (second embodiment), wherein the pharmaceutically active component induces a specific immune response (e.g. an antigen). The present invention relates likewise to the use of a nucleic acid of the invention or a pharmaceutical composition according to the invention for the treatment of infectious diseases, autoimmune diseases, allergies or cancer diseases.
- -
-
Paragraph 0177-0184
(2020/02/05)
-
- BENZO[C][1,2,5]OXADIAZOLE FOR THE TREATMENT OF DISEASES CAUSED BY HELICOBACTER
-
The present invention relates to new compounds which are benzo[c][1,2,5]oxadiazole derivatives, and the use thereof in the treatment of infectious diseases caused by Helicobacter pylori. Also, the present invention relates to a pharmaceutical composition
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-
Page/Page column 16-17
(2020/12/07)
-
- A Novel Agonist of the Type 1 Lysophosphatidic Acid Receptor (LPA1), UCM-05194, Shows Efficacy in Neuropathic Pain Amelioration
-
Neuropathic pain (NP) is a complex chronic pain state with a prevalence of almost 10% in the general population. Pharmacological options for NP are limited and weakly effective, so there is a need to develop more efficacious NP attenuating drugs. Activation of the type 1 lysophosphatidic acid (LPA1) receptor is a crucial factor in the initiation of NP. Hence, it is conceivable that a functional antagonism strategy could lead to NP mitigation. Here we describe a new series of LPA1 agonists among which derivative (S)-17 (UCM-05194) stands out as the most potent and selective LPA1 receptor agonist described so far (Emax = 118%, EC50 = 0.24 μM, KD = 19.6 nM; inactive at autotaxin and LPA2-6 receptors). This compound induces characteristic LPA1-mediated cellular effects and prompts the internalization of the receptor leading to its functional inactivation in primary sensory neurons and to an efficacious attenuation of the pain perception in an in vivo model of NP.
- González-Gil, Inés,Zian, Debora,Vázquez-Villa, Henar,Hernández-Torres, Gloria,Martínez, R. Fernando,Khiar-Fernández, Nora,Rivera, Richard,Kihara, Yasuyuki,Devesa, Isabel,Mathivanan, Sakthikumar,Del Valle, Cristina Rosell,Zambrana-Infantes, Emma,Puigdomenech, María,Cincilla, Giovanni,Sanchez-Martinez, Melchor,Rodríguez De Fonseca, Fernando,Ferrer-Montiel, Antonio V.,Chun, Jerold,López-Vales, Rubén,López-Rodríguez, María L.,Ortega-Gutiérrez, Silvia
-
supporting information
p. 2372 - 2390
(2020/01/02)
-
- Synthesis and antimicrobial screening of novel 1,3-dioxolanes linked to N-5 of 5H-1,2,4-triazino[5,6-b]indole-3-thiol
-
Synthesis of 1-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-1H-indole-2,3-dione (10) was achieved by coupling 1H-indole-2,3-dione (16) with (R)-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (15) in the presence of sodium hydride in dry N,N-dimethylformamide at room temperature in a closed Erlenmeyer flask. Condensation of 10 with hydrazinecarbothioamide in water afforded the thiosemicarbazone derivative 17; its subsequent cyclization with potassium carbonate in water gave the corresponding thione 18 in good yield. The 3-allylthio and 3-benzylthio derivatives 20 and 21 were also prepared by alkylating thiol 19 with alkyl halides in aqueous sodium hydroxide or coupling of 3-(allylthio/benzylthio)-5H-1,2,4-triazino[5,6-b]indoles (23 and 24) with compound 15 in NaH/DMF. Compound 20 was isomerized to a mixture of geometrical isomers (E/Z)-5-[(2,2-dimethyl-1,3-dioxolan-4-yl)-methyl]-3-(prop-1-en-1-ylthio)-5H-1,2,4-triazino[5,6-b]indoles (25 and 26), evidenced by their 1H- and 13C-NMR spectra taken in deuterodimethyl sulfoxide. Structural elucidation of the synthesized compounds was realized using FT-IR, 1H-NMR, 13C-NMR, mass spectrometry and elemental analysis. The newly synthesized compounds were found to possess moderate inhibitory activity against the fungus Candida albicans compared to clotrimazole as reference control. Compounds 10, 17, 19, 20, 21, 23 and 24 had mean growth inhibition zones (IZ) and minimal inhibitory concentrations (MIC) in the range of 12–15 mm and 31.25–200 μg mL-1, respectively, with inhibition levels in the range 70.58–88.23 %. Compound 19 exhibited moderate activity against Gram-positive bacteria Staphylococcus aureus relative to imipenem as the standard drug. All compounds were inactive against Escherichia coli and Pseudomonas aeruginosa.
- Ramadan, El Sayed,Rasheed, Hanaa A.,El Ashry, El Sayed H.
-
-
- Water-soluble meroterpenes containing an aminoglyceride fragment with geraniol residues: synthesis and membranotropic properties
-
A number of new membrane anchors based on water-soluble aminoglycerides with geraniol fragments have been synthesized. A biomimetic approach was used based on the design of meroterpenes structurally similar to archaeal lipids. Turbidimetry and laser Doppler microelectrophoresis showed that the synthesized compounds were incorporated into unilamellar dipalmitoylphosphatidylcholine (DPPC) vesicles.
- Akhmedov, Alan A.,Shurpik, Dmitry N.,Plemenkov, Vitaliy V.,Stoikov, Ivan I.
-
-
- Compound containing ferrocene base element and preparation method and application of compound
-
The invention discloses a compound containing a ferrocene base element and a preparation method and application of the compound. A structure formula of the compound containing the ferrocene base element is shown in a formula I. The formula I is shown in the description.
- -
-
Paragraph 0062-0067
(2019/02/10)
-
- Discovery of novel potent HCV NS5B polymerase non-nucleoside inhibitors bearing a fused benzofuran scaffold
-
This letter describes the discovery of a fused benzofuran scaffold viable for preparing a series of novel potent HCV NS5B polymerase non-nucleoside inhibitors. Designed on the basis of the functionalized benzofuran derivative nesbuvir (HCV-796), these com
- Zhong, Min,Peng, Eric,Huang, Ningwu,Huang, Qi,Huq, Anja,Lau, Meiyen,Colonno, Richard,Li, Leping
-
supporting information
p. 963 - 968
(2018/02/09)
-
- Synthesis of alkyl-glycerolipids standards for gas chromatography analysis: Application for chimera and shark liver oils
-
Natural O-alkyl-glycerolipids, also known as alkyl-ether-lipids (AEL), feature a long fatty alkyl chain linked to the glycerol unit by an ether bond. AEL are ubiquitously found in different tissues but, are abundant in shark liver oil, breast milk, red blood cells, blood plasma, and bone marrow. Only a few AEL are commercially available, while many others with saturated or mono-unsaturated alkyl chains of variable length are not available. These compounds are, however, necessary as standards for analytical methods. Here, we investigated different reported procedures and we adapted some of them to prepare a series of 1-O-alkyl-glycerols featuring mainly saturated alkyl chains of various lengths (14:0, 16:0, 17:0, 19:0, 20:0, 22:0) and two monounsaturated chains (16:1, 18:1). All of these standards were fully characterized by NMR and GC-MS. Finally, we used these standards to identify the AEL subtypes in shark and chimera liver oils. The distribution of the identified AEL were: 14:0 (20–24%), 16:0 (42–54%) and 18:1 (6–16%) and, to a lesser extent, (0.2–2%) for each of the following: 16:1, 17:0, 18:0, and 20:0. These standards open the possibilities to identify AEL subtypes in tumours and compare their composition to those of non-tumour tissues.
- Pinault, Michelle,Guimaraes, Cyrille,Couthon, Hélène,Thibonnet, Jér?me,Fontaine, Delphine,Chant?me, Aurélie,Chevalier, Stephan,Besson, Pierre,Jaffrès, Paul-Alain,Vandier, Christophe
-
-
- HYDROPHILIC FLUORINATED MOLECULES FOR LIPOSOMAL 19F MRI PROBES WITH UNIQUE MR SIGNATURES
-
Readily available hydrophilic and small organofluorine moieties were condensed via “click chemistry” to generate nonionic hydrophilic fluorinated molecules with unique 19F MR signatures. These were used to fabricate stable liposome formulations for imaging various tissue types. This approach was tailored to exploit the broad spectrum of organic 19F molecular species and to generate probes with distinct 19F MRI signatures for simultaneous assessment of multiple molecular targets within the same target volume.
- -
-
Paragraph 0103
(2018/06/15)
-
- A novel convergent synthesis of the potent antiglaucoma agent tafluprost
-
Tafluprost (AFP-168, 5) is a unique 15-deoxy-15,15-difluoro-16-phenoxy prostaglandin F2α (PGF2α) analog used as an efficacious ocular hypotensive agent in the treatment of glaucoma and ocular hypertension, as monotherapy, or as adjunctive therapy to β-blockers. A novel convergent synthesis of 5 was developed employing Julia-Lythgoe olefination of the structurally advanced prostaglandin phenylsulfone 16, also successfully applied for manufacturing of pharmaceutical grade latanoprost (2), travoprost (3) and bimatoprost (4), with an aldehyde !-chain synthon 17. The use of the same prostaglandin phenylsulfone 16, as a starting material in parallel syntheses of all commercially available antiglaucoma PGF2α analogs 2-5, significantly reduces manufacturing costs resulting from its synthesis on an industrial scale and development of technological documentation. Another key aspect of the route developed is deoxydifluorination of a trans-13,14-en-15-one 30 with Deoxo-Fluor. Subsequent hydrolysis of protecting groups and final esterification of acid 6 yielded tafluprost (5). The main advantages are the preparation of high purity tafluprost (5) and the application of comparatively cheap reagents. The preparation and identification of two other tafluprost acid derivatives, tafluprost methyl ester (32) and tafluprost ethyl amide (33), are also described.
- Krupa, Ma?gorzata,Chodyński, Micha?,Ostaszewska, Anna,Cmoch, Piotr,Dams, Iwona
-
supporting information
(2017/03/09)
-
- COMPOSITIONS AND METHODS FOR DELIVERY OF THERAPEUTIC AGENTS
-
This disclosure provides improved lipid-based compositions, including lipid nanoparticle compositions, and methods of use thereof for delivering agents in vivo including nucleic acids and proteins. These compositions are not subject to accelerated blood clearance and they have an improved toxicity profile in vivo.
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-
Page/Page column 349-350
(2017/07/18)
-
- Synthesis of novel glycerol-derived 1,2,3-triazoles and evaluation of their fungicide, phytotoxic and cytotoxic activities
-
The synthesis of a series of 1,2,3-triazoles using glycerol as starting material is described. The key step in the preparation of these triazolic derivatives is the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), also known as click reaction, between 4-(azidomethyl)-2,2-dimethyl-1,3- dioxolane (3) and different terminal alkynes. The eight prepared derivatives were evaluated with regard to their fungicide, phytotoxic and cytotoxic activities. The fungicidal activity was assessed in vitro against Colletotrichum gloeosporioides, the causative agent of papaya anthracnose. It was found that the compounds 1-(1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-1,2,3-triazol-4-yl)- cyclo-hexanol (4g) and 2-(1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-1,2,3-triazol-4-yl)propan-2-ol (4h) demonstrated high efficiency in controlling C. gloeosporioides when compared to the commercial fungicide tebuconazole. The triazoles did not present any phytotoxic effect when evaluated against Lactuca sativa. However, five derivatives were mitodepressive, inducing cell death detected by the presence of condensed nuclei and acted as aneugenic agents in the cell cycle of L. sativa. It is believed that glycerol derivatives bearing 1,2,3-triazole functionalities may represent a promising scaffold to be explored for the development of new agents to control C. gloeosporioides.
- Costa, Adilson Vidal,De Oliveira, Marcos Vinicius Lacerda,Pinto, Roberta Trist?o,Moreira, Luiza Carvalheira,Gomes, Ediellen Mayara Corrêa,De Assis Alves, Thammyres,Pinheiro, Patrícia Fontes,De Queiroz, Vagner Tebaldi,Vieira, Larissa Fonseca Andrade,Teixeira, Robson Ricardo,De Jesus, Waldir Cintra
-
-
- COMPOUNDS AND COMPOSITIONS FOR RADIATION THERAPY AND METHODS OF USING THE SAME
-
The present disclosure relates to bisphenol ether derivatives and compositions thereof, which can be useful in radiation therapy for treatment of diseases, such as prostate cancer. In particular, the compounds of the present disclosure containing a radiolabeled atom can be useful in targeted delivery of radionuclides for treatment of lesions, tumors, and/or cancer cells.
- -
-
Paragraph 293
(2018/01/15)
-
- BISPHENOL DERIVATIVES AND THEIR USE AS ANDROGEN RECEPTOR ACTIVITY MODULATORS
-
Compounds having a structure of Formula I: or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein R1, R2, R3, R11a, R11b, R11c, R11d, and X, are as defined herein, are provided. Uses of such compounds for modulating androgen receptor activity, imaging diagnostics in cancer and therapeutics, and methods for treatment of subjects in need thereof, including prostate cancer are also provided.
- -
-
Paragraph 0271
(2017/11/07)
-
- SMALL MOLECULE INHIBITORS OF FIBROSIS
-
Described herein are compounds and compositions for the treatment of a fibrotic disease.
- -
-
Paragraph 00471
(2016/06/28)
-
- Repurposing the Clinically Efficacious Antifungal Agent Itraconazole as an Anticancer Chemotherapeutic
-
Itraconazole (ITZ) is an FDA-approved member of the triazole class of antifungal agents. Two recent drug repurposing screens identified ITZ as a promising anticancer chemotherapeutic that inhibits both the angiogenesis and hedgehog (Hh) signaling pathways. We have synthesized and evaluated first- and second-generation ITZ analogues for their anti-Hh and antiangiogenic activities to probe more fully the structural requirements for these anticancer properties. Our overall results suggest that the triazole functionality is required for ITZ-mediated inhibition of angiogenesis but that it is not essential for inhibition of Hh signaling. The synthesis and evaluation of stereochemically defined des-triazole ITZ analogues also provides key information as to the optimal configuration around the dioxolane ring of the ITZ scaffold. Finally, the results from our studies suggest that two distinct cellular mechanisms of action govern the anticancer properties of the ITZ scaffold.
- Pace, Jennifer R.,Deberardinis, Albert M.,Sail, Vibhavari,Tacheva-Grigorova, Silvia K.,Chan, Kelly A.,Tran, Raymond,Raccuia, Daniel S.,Wechsler-Reya, Robert J.,Hadden, M. Kyle
-
supporting information
p. 3635 - 3649
(2016/05/24)
-
- Facile and efficient synthesis of [18 F]Fluoromisonidazole using novel 2-nitroimidazole derivatives
-
[81F]Fluoromisonidazole ([ ([81F]FMISO) is a hypoxia imaging marker utilized in positron emission tomography. Novel FMISO precursors were prepared from a commercially available material, and several reaction factors that affect synthesis of [ [81F]FMISO were examined to achieve a higher fluorination yield. [18 F]FMISO was obtained from radiosynthesis, followed by the hydrolysis of protecting groups with HCl. New 2-nitroimidazole precursor showed a higher [18 F]fluorination and a higher synthetic yield. This result provided alternative guidelines for the preparation of hypoxia imaging marker.
- Kwon, Young-Do,Jung, Yongju,Lim, B Seok Tae,Sohna, Myung-Hee,Kim, Hee-Kwon
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p. 1150 - 1156
(2016/08/16)
-
- Synthesis and properties of brassinosteroid biosynthesis inhibitor fluorescent probe with dansyl moiety
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Brassinosteroids (BRs) are important plant hormones that play key roles in plant development and defense responses to environmental cues. To explore the inhibition mechanism of BR biosynthesis, we report the synthesis of novel triazole derivatives with da
- Hoshi, Tomoki,Yoshizawa, Yuko,Oh, Keimei
-
p. 220 - 225
(2016/03/15)
-
- COMPOSITIONS USEFUL FOR TREATING DISORDERS RELATED TO KIT
-
Compounds and compositions useful for treating disorders related to KIT and PDFGR are described herein.
- -
-
Paragraph 0159; 0160; 0161
(2015/04/28)
-
- PROCESS FOR PREPARATION OF PROSTAGLANDIN F2 ALPHA ANALOGUES
-
A convergent synthesis of the prostaglandin F2α analogues, travoprost and bimatoprost, was developed employing Julia-Lythgoe olefination of the structurally advanced phenylsulfone with an enantiomerically pure aldehyde ω-chain synthon. The novel convergent strategy allows the synthesis of a whole series of prostaglandin analogues of high purity from a common and structurally advanced prostaglandin intermediate.
- -
-
Paragraph 0221; 0222
(2015/02/19)
-
- HALOGENATED COMPOUNDS FOR CANCER IMAGING AND TREATMENT AND METHODS FOR THEIR USE
-
Compounds having a structure of Formula I: (Formula (I)) or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein R1, R2, R 3, R4, R5, X1, X2, X3 and X4 are as defined herein, and wherein the compound comprises at least one F, CI, Br, I or 123I moiety, are provided. Uses of such compounds for imaging diagnostics in cancer and therapeutics methods for treatment of subjects in need thereof, including prostate cancer as well as methods and intermediates for preparing such compounds are also provided.
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-
Page/Page column 52-53
(2015/03/28)
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- A Clickable and Photocleavable Lipid Analogue for Cell Membrane Delivery and Release
-
For drug delivery purposes, the ability to conveniently attach a targeting moiety that will deliver drugs to cells and then enable controlled release of the active molecule after localization is desirable. Toward this end, we designed and synthesized clickable and photocleavable lipid analogue 1 to maximize the efficiency of bioconjugation and triggered release. This compound contains a dibenzocyclooctyne group for bioorthogonal derivatization linked via a photocleavable 2-nitrobenzyl moiety at the headgroup of a synthetic lipid backbone for targeting to cell membranes. To assess delivery and release using this system, we report fluorescence-based assays for liposomal modification and photocleavage in solution as well as through surface immobilization to demonstrate successful liposome functionalization and photoinduced release. In addition, fluorophore delivery to and release from live cells was confirmed and characterized using fluorescence microscopy and flow cytometry analysis in which 1 was delivered to cells, derivatized, and photocleaved. Finally, drug delivery studies were performed using an azide-tagged analogue of camptothecin, a potent anticancer drug that is challenging to deliver due to poor solubility. In this case, the ester attachment of the azide tag acted as a caging group for release by intracellular esterases rather than through photocleavage. This resulted in a dose-dependent response in the presence of liposomes containing delivery agent 1, confirming the ability of this compound to stimulate delivery to the cytoplasm of cells.
- Alam, Shahrina,Alves, Daiane S.,Whitehead, Stuart A.,Bayer, Andrew M.,McNitt, Christopher D.,Popik, Vladimir V.,Barrera, Francisco N.,Best, Michael D.
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p. 1021 - 1031
(2015/06/30)
-
- 2-ALKYL-OR-ARYL-SUBSTITUTED TANSHINONE DERIVATIVES, AND PREPARATION METHOD AND APPLICATION THEREOF
-
The present invention belongs to the field of natural medicine and pharmaceutical chemistry, and specifically relates to novel 2-alkyl- or 2-aromatic-substituted tanshinone I derivatives of formula (I) or a pharmaceutically acceptable salt thereof, to a process for the preparation of these compounds, compositions containing such compounds and their use in preparing antineoplastic medicaments. When Z=R, said derivative is 2-alkyl-substituted tanshinone I; when Z=Ar, said derivative is 2-aryl-substituted tanshinone I; when Z=Het, said derivative is 2-heteroaryl- or 2-heterocyclyl-substituted tanshinone I.
- -
-
Paragraph 0091; 0092
(2014/10/16)
-
- Synthesis and self-assembly of polyhydroxylated and electropolymerizable block copolymers
-
A facile synthetic strategy for preparing hydroxylated polymethacrylate amphiphilic block copolymers (PCzMMA-b-PBMMA, PFlMMA-b-PBMMA) incorporated with primary and secondary hydroxyl groups and electroactive moieties along the polymer backbone is reported
- Barik, Satyananda,Valiyaveettil, Suresh
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p. 2217 - 2227
(2014/07/08)
-
- 2-ALKYL-OR-ARYL-SUBSTITUTED TANSHINONE DERIVATIVES, AND PREPARATION METHOD AND APPLICATION THEREOF
-
The present invention belongs to the field of natural medicine and pharmaceutical chemistry, and specifically relates to novel 2-alkyl- or 2-aromatic-substituted tanshinone I derivatives of formula (I) or a pharmaceutically acceptable salt thereof, to a process for the preparation of these compounds, compositions containing such compounds and their use in preparing antineoplastic medicaments. When Z═R, said derivative is 2-alkyl-substituted tanshinone I; when Z═Ar, said derivative is 2-aryl-substituted tanshinone I; when Z=Het, said derivative is 2-heteroaryl- or 2-heterocyclyl-substituted tanshinone I.
- -
-
Paragraph 0116; 0117
(2014/11/27)
-
- Synthesis of novel chiral TBBt derivatives with hydroxyl moiety. Studies on inhibition of human protein kinase CK2α and cytotoxicity properties
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The efficient method for the synthesis of novel 4,5,6,7-tetrabromo-1H- benzotriazole (TBBt) derivatives bearing a single stereogenic center has been developed. New compounds with a variety of substituents at the meta- and para-position of the phenyl ring are reported. All of the presented compounds were obtained using classical synthetic methods, such as bromination of benzotriazole, and its subsequent alkylation by monotosylated arylpropane-1,3-diols, which in turn have been synthesized through reduction of the corresponding prochiral β-keto esters, and the selective monotosylation of the primary hydroxyl group. The influence of the new and previously reported N-hydroxyalkyl TBBt derivatives on the activity of human protein kinase CK2α catalytic subunit was examined. The most active were derivatives with N-hydroxyalkyl substituents (IC50 in 0.80-7.35 μM range). A binding mode of (R)-1-(4,5,6,7-tetrabromo-2H-benzotriazol-2-yl)butan-3-ol 7b to hCK2α has been proposed based on in silico docking studies. Additionally, MTT-based cytotoxicity tests demonstrated high activities of novel 1-aryl-3-TBBt-propan-1-ol and 3-TBBt-propan-1,2-diol derivatives against human peripheral blood T lymphoblast (CCRF-CEM), and moderate anti-tumor activities against human breast adenocarcinoma (MCF7) cell lines.
- Borowiecki, Pawe?,Wawro, Adam M.,Wińska, Patrycja,Wielechowska, Monika,Bretner, Maria
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supporting information
p. 364 - 374
(2014/08/05)
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- SMALL MOLECULE INHIBITORS OF FIBROSIS
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Described herein are compounds and compositions for the treatment of a fibrotic disease.
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Paragraph 00333; 00335
(2015/01/06)
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- NOVEL COMPOUND FOR IMAGING TAU PROTEIN ACCUMULATED IN THE BRAIN
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The present invention provides a compound represented by the following formula (I), a pharmaceutically acceptable salt thereof, or a solvate thereof. wherein: R1 and R2 are each separately selected from the group consisting of hydrog
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Paragraph 0306
(2014/09/02)
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- A novel convergent synthesis of the potent antiglaucoma agent travoprost
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The 16-(3-trifluoromethyl)phenoxy PGF2α analogue travoprost (8a) has potent topical ocular activity. A novel convergent synthesis of 13,14-en-15-ol PGF2α analogues was developed employing Julia-Lythgoe olefination of the structurally advanced prostaglandin phenylsulfone (5Z)-(+)-15 with a new enantiomerically pure aldehyde ω-chain synthon (S)-(-)-16a. Subsequent hydrolysis of protecting groups and final esterification of fluprostenol (7a) yielded travoprost (8a). The main advantages are the preparation of high purity travoprost (8a) and the application of comparatively cheap reagents. The novel convergent strategy allows the synthesis of a whole series of 13,14-en-15-ol PGF2α analogues from a common and structurally advanced prostaglandin intermediate 15. The preparation and identification of two synthetic impurities, 15-epi isomer (8b) of travoprost and a new prostaglandin related ester (5Z)-(+)-18, are also described.
- Dams, Iwona,Chodyński, Micha?,Krupa, Ma?gorzata,Pietraszek, Anita,Zezula, Marta,Cmoch, Piotr,Kosińska, Monika,Kutner, Andrzej
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p. 1634 - 1648
(2013/02/26)
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- Asymmetric synthesis and effect of absolute stereochemistry of YCZ-2013, a brassinosteroid biosynthesis inhibitor
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The four stereoisomers of 2RS,4RS-1-[[2-(2,4-dichlorophenyl)-4-(2-(2- propenyloxy)phenoxymethyl)-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole (YCZ-2013), a novel brassinosteroid biosynthesis inhibitor, were prepared. The diastereomers of 2RS,4R-5 and 2RS,4S-5 were prepared by using the corresponding optically pure R and S toluene-4-sulfonic acid 2,3-dihydroxypropyl ester (R-4,S-4). The enatiomerically and diastereomerically pure acetonide (5) was obtained by a method involving diastereoselective crystallisation of the tosylate salt, followed by re-equilibration with the mother liquor and chromatography. The optical purity of four target compounds (YCZ-2013) was confirmed by chiral high-performance liquid chromatography (HPLC) and NMR. The effects of these stereoisomers on Arabidopsis stem elongation indicated that the cis isomers of 2S,4R-YCZ-2013 and 2R,4S-YCZ-2013 exhibited potent inhibitory activity with IC50 values of approximately 24 ± 3 and 24 ± 2 nM, respectively. The IC50 values of the trans isomers of 2S,4S-YCZ-2013 and 2R,4R-YCZ-2013 are approximately 1510 ± 50 and 3900 ± 332 nM, respectively. Co-application of brassinolide (10 nM), the most potent BR, and GA3 (1 μM) to Arabidopsis seedlings grown in the dark with 2R,4S-YCZ-2013 and 2S,4R-YCZ-2013 revealed that brassinolide recovered the induced dwarfism of Arabidopsis seedlings, whereas GA3 showed no effect.
- Oh, Keimei,Yamada, Kazuhiro,Yoshizawa, Yuko
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p. 6915 - 6919
(2014/01/06)
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- Synthesis and biological evaluation of novel azole derivatives as selective potent inhibitors of brassinosteroid biosynthesis
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Brassinosteroids (BRs) are phytohormones that control several important agronomic traits, such as flowering, plant architecture, seed yield, and stress tolerance. To manipulate the BR levels in plant tissues using specific inhibitors of BR biosynthesis, a series of novel azole derivatives were synthesized and their inhibitory activity on BR biosynthesis was investigated. Structure-activity relationship studies revealed that 2RS, 4RS-1-[4-(2- allyloxyphenoxymethyl)-2-(4-chlorophenyl)-[1,3]dioxolan-2-ylmethyl]-1H-[1,2,4] triazole (G2) is a highly selective inhibitor of BR biosynthesis, with an IC50 value of approximately 46 ± 2 nM, which is the most potent BR biosynthesis inhibitor observed to date. Use of gibberellin (GA) biosynthesis mutants and BR signaling mutants to analyze the mechanism of action of this synthetic series indicated that the primary site of action is BR biosynthesis. Experiments feeding BR biosynthesis intermediates to chemically treated Arabidopsis seedlings suggested that the target sites of this synthetic series are CYP90s, which are responsible for the C-22 and/or C-23 hydroxylation of campesterol.
- Yamada, Kazuhiro,Yajima, Osamu,Yoshizawa, Yuko,Oh, Keimei
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p. 2451 - 2461
(2013/06/27)
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- Enantioselective total synthesis of macrolide (+)-neopeltolide
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The asymmetric total synthesis of the anti-proliferative macrolide (+)-neopeltolide has been completed. The stereochemically defined trisubstituted tetrahydropyran ring was constructed via a catalytic hetero-Diels-Alder reaction creating two new chiral ce
- Ghosh, Arun K.,Shurrush, Khriesto A.,Dawson, Zachary L.
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p. 7768 - 7777
(2013/11/06)
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- PROCESS FOR PREPARATION OF PROSTAGLANDIN F2α ANALOGUES
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A convergent synthesis of the prostaglandin F2α analogues, travoprost and bimatoprost, was developed employing Julia-Lythgoe olefination of the structurally advanced phenylsulfone with an enantiomerically pure aldehyde ω-chain synthon. The novel convergent strategy allows the synthesis of a whole series of prostaglandin analogues of high purity from a common and structurally advanced prostaglandin intermediate.
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Page/Page column 33; 34
(2013/09/26)
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- Synthesis of phosphonoglycine backbone units for the development of phosphono peptide nucleic acids
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A series of phosphono-modified backbone mimics based on achiral and chiral N-(dihydroxypropyl)glycine units were obtained by sequential addition of phosphonate and nucleobase moieties to suitably protected dihydroxypropylamines. Simple synthetic strategies enabled the preparation of various target derivatives that will be useful as building blocks for the preparation of new synthetic polymers containing a phosphonate internucleotide linkage in place of the standard phosphodiester bond. Copyright
- Doboszewski, Bogdan,Groaz, Elisabetta,Herdewijn, Piet
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p. 4804 - 4815
(2013/08/23)
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- Synthesis of novel brassinosteroid biosynthesis inhibitors based on the ketoconazole scaffold
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Brassinosteroids (BRs) are steroidal plant hormones that control several important agronomic traits such as plant architecture, seed yield, and stress tolerance. Inhibitors that target BR biosynthesis are candidate plant growth regulators. We synthesized
- Oh, Keimei,Yamada, Kazuhiro,Asami, Tadao,Yoshizawa, Yuko
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supporting information; experimental part
p. 1625 - 1628
(2012/04/04)
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- Synthesis and properties of trialkyl(2,3-dihydroxypropyl)phosphonium salts, a new class of hydrophilic and hydrophobic glyceryl-functionalized ILs
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A series of new ionic liquids (ILs) based on trialkylglycerylphosphonium cations have been prepared starting from 3-chloropropane-1,2-diol or (2,2-dimethyl-1,3-dioxolan-4-yl)methanol, two compounds readily obtainable from glycerol (a widely available and
- Bellina, Fabio,Chiappe, Cinzia,Lessi, Marco
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scheme or table
p. 148 - 155
(2012/03/27)
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- Transporting excess electrons along potential energy gradients provided by 2 ' -deoxyuridine derivatives in dna
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LUMO-level dependent: Chemically modified DNA molecules containing 2'-deoxyuridine (dU) derivatives with various LUMO energy levels have been synthesized to manipulate electron-transfer efficiencies. By arranging thymidine, the dU derivatives, and 5-fluor
- Ito, Takeo,Hamaguchi, Yuta,Tanabe, Kazuhito,Yamada, Hisatsugu,Nishimoto, Sei-Ichi
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supporting information; experimental part
p. 7558 - 7561
(2012/10/18)
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- AMINOGLYCOSIDE DERIVATIVES
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The present invention relates to antimicrobial and antibiotic aminoglycoside derivatives. The compounds of the present application have the following chemical structures. The invention also relates to compositions, methods of preparation and methods of treatment of bacterial infections using the above aminoglycoside derivative.
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Page/Page column 50
(2011/12/02)
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- RNA-SELECTIVE HYBRIDIZATION REAGENT AND UTILIZATION OF THE SAME
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Provided is a nucleoside derivative which has a high affinity for RNA. Use is made of a nucleoside derivative represented by either formula (1) or formula (2). (In formulae (1) and (2), Z represents a carbon atom or a nitrogen atom; R1 represen
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Page/Page column 14; 15
(2011/01/12)
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- Structure-activity relationships in toll-like receptor-2 agonistic diacylthioglycerol lipopeptides
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The N-termini of bacterial lipoproteins are acylated with a (S)-(2,3-bisacyloxypropyl)cysteinyl residue. Lipopeptides derived from lipoproteins activate innate immune responses by engaging Toll-like receptor 2 (TLR2) and are highly immunostimulatory and yet without apparent toxicity in animal models. The lipopeptides may therefore be useful as potential immunotherapeutic agents. Previous structure-activity relationships in such lipopeptides have largely been obtained using murine cells, and it is now clear that significant species-specific differences exist between human and murine TLR responses. We have examined in detail the role of the highly conserved Cys residue as well as the geometry and stereochemistry of the Cys-Ser dipeptide unit. (R)-Diacylthioglycerol analogues are maximally active in reporter gene assays using human TLR2. The Cys-Ser dipeptide unit represents the minimal part-structure, but its stereochemistry was found not to be a critical determinant of activity. The thioether bridge between the diacyl and dipeptide units is crucial, and replacement by an oxoether bridge results in a dramatic decrease in activity.
- Wu, Wenyan,Li, Rongti,Malladi, Subbalakshmi S.,Warshakoon, Hemamali J.,Kimbrell, Matthew R.,Amolins, Michael W.,Ukani, Rehman,Datta, Apurba,David, Sunil A.
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experimental part
p. 3198 - 3213
(2010/10/02)
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- Process for the manufacture of polyol perfluoropolyether derivative
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A process for the manufacture of a polyol (per)fluoropolyether derivative, comprising: 1. reacting at least one triol having two protected hydroxyl functions and a free hydroxyl group with an activating agent, to yield an activated protected triol; 2. reacting the activated protected triol with a functional (per)fluoropolyether derivative of formula: T2-O—Rf-T1, wherein: Rf represents a fluoropolyoxyalkene chain which is a fluorocarbon segment comprising ether linkages in main chain; T1 and T2, equal to or different from each other, are independently selected from non-functional groups of formula: —CF3, —CF2—CF3, —CF2Cl, —CF2CF2Cl, —CF2—COF, —COF: and functional hydroxyl groups comprising at least one hydroxyl group, with the provisio that at least one of T1 and T2 is a functional hydroxyl group as above detailed to yield a protected polyol (per)fluoropolyether derivative; and 3. deprotecting the protected polyol (per)fluoropolyether derivative to yield the polyol (per)fluoropolyether derivative.
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Page/Page column 6
(2010/10/03)
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- BENZIMIDAZOLES AND RELATED ANALOGS AS SIRTUIN MODULATORS
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Provided herein are sirtuin-modulating compounds of formula (II) The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.
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Page/Page column 86
(2010/04/03)
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- Synthesis of hybrid 1,2,3-triazolo-δ-lactams/lactones using Huisgen [3+2] cycloaddition 'click-chemistry' in water
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The synthesis of a new class of hybrid 1,2,3-triazozlo-δ-lactams/lactones has been achieved using the Huisgen [3+2] dipolar cycloaddition 'click-chemistry' reaction of various organic azides with an activated alkyne in water, followed by cyclization.
- Kumar, Indresh,Rana, Sravendra,Cho, Jae Whan,Rode, Chandrashekhar V.
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scheme or table
p. 352 - 355
(2010/06/16)
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- Mycolic Acids Constitute a Scaffold for Mycobacterial Lipid Antigens Stimulating CD1-Restricted T Cells
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CD1-restricted lipid-specific T lymphocytes are primed during infection with Mycobacterium tuberculosis, the causative agent of tuberculosis. Here we describe the antigenicity of glycerol monomycolate (GroMM), which stimulates CD1b-restricted CD4+/s
- Layre, Emilie,Collmann, Anthony,Bastian, Max,Mariotti, Sabrina,Czaplicki, Jerzy,Prandi, Jacques,Mori, Lucia,Stenger, Steffen,De Libero, Gennaro,Puzo, Germain,Gilleron, Martine
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experimental part
p. 82 - 92
(2010/06/16)
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