- Synthesis of alkyl-glycerolipids standards for gas chromatography analysis: Application for chimera and shark liver oils
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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
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Read Online
- 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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Read Online
- Selective catalytic oxidation of diglycerol
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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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Read Online
- Selective targeting of human and animal pathogens of the helicobacter genus by flavodoxin inhibitors: Efficacy, synergy, resistance and mechanistic studies
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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
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- Ammonium Chloride-Promoted Rapid Synthesis of Monosubstituted Ureas under Microwave Irradiation
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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
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supporting information
p. 5135 - 5146
(2021/10/19)
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- Synthesis of glycerol-derived 4-alkyl-substituted 1,2,3-triazoles and evaluation of their fungicidal, phytotoxic, and antiproliferative activities
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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.
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p. 821 - 832
(2020/04/27)
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- NUCLEIC ACID OF FORMULA (I): GlXmGn, OR (II): ClXmCn, IN PARTICULAR AS AN IMMUNE-STIMULATING AGENT/ADJUVANT
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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.
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Paragraph 0177-0184
(2020/02/05)
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- BENZO[C][1,2,5]OXADIAZOLE FOR THE TREATMENT OF DISEASES CAUSED BY HELICOBACTER
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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)
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- Water-soluble meroterpenes containing an aminoglyceride fragment with geraniol residues: synthesis and membranotropic properties
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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.
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- HYDROPHILIC FLUORINATED MOLECULES FOR LIPOSOMAL 19F MRI PROBES WITH UNIQUE MR SIGNATURES
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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.
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Paragraph 0103
(2018/06/15)
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- A novel convergent synthesis of the potent antiglaucoma agent tafluprost
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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
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supporting information
(2017/03/09)
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- COMPOSITIONS AND METHODS FOR DELIVERY OF THERAPEUTIC AGENTS
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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)
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- Synthesis of novel glycerol-derived 1,2,3-triazoles and evaluation of their fungicide, phytotoxic and cytotoxic activities
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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
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- Repurposing the Clinically Efficacious Antifungal Agent Itraconazole as an Anticancer Chemotherapeutic
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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
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supporting information
p. 3635 - 3649
(2016/05/24)
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- Facile and efficient synthesis of [18 F]Fluoromisonidazole using novel 2-nitroimidazole derivatives
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[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)
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- 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
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p. 220 - 225
(2016/03/15)
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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 00455
(2016/06/28)
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- COMPOSITIONS USEFUL FOR TREATING DISORDERS RELATED TO KIT
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Compounds and compositions useful for treating disorders related to KIT and PDFGR are described herein.
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Paragraph 0159; 0160; 0161
(2015/04/28)
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- 2-ALKYL-OR-ARYL-SUBSTITUTED TANSHINONE DERIVATIVES, AND PREPARATION METHOD AND APPLICATION THEREOF
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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.
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Paragraph 0091; 0092
(2014/10/16)
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- Synthesis and self-assembly of polyhydroxylated and electropolymerizable block copolymers
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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)
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- 2-ALKYL-OR-ARYL-SUBSTITUTED TANSHINONE DERIVATIVES, AND PREPARATION METHOD AND APPLICATION THEREOF
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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.
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Paragraph 0116; 0117
(2014/11/27)
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- 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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- 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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- 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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- 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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- 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 and in vitro photodynamic activities of di-α-substituted zinc(ii) phthalocyanine derivatives
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A new series of di-α-substituted zinc(ii) phthalocyanine derivatives have been prepared by mixed cyclisation of the corresponding 1,4-disubstituted phthalonitriles or naphthalonitriles with an excess of unsubstituted phthalonitrile in the presence of Zn(O
- Liu, Jian-Yong,Lo, Pui-Chi,Jiang, Xiong-Jie,Fong, Wing-Ping,Ng, Dennis K. P.
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scheme or table
p. 4129 - 4135
(2009/09/04)
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- Nucleic Acid of Formula (I): GIXmGn, or (II): CIXmCn, in Particular as an Immune-Stimulating Agent/Adjuvant
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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.
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- Ring-opening reactions of epoxides catalyzed by molybdenum(VI) dichloride dioxide
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Transformation of epoxides to β-alkoxy alcohols, acetonides, and α-alkoxy ketones is achieved by using molybdenum(VI) dichloride dioxide (MoO2Cl2) as a catalyst. Alcohol, aldehyde, oxime, tosyl, and tert-butyldimethylsilyl functional groups are tolerated during the methanolysis and acetonidation of the functionalized epoxides. No polymerization product is observed with any of the epoxides. Direct conversion of epoxides devoid of sensitive functional groups into the corresponding α-methoxy ketone is achieved in a single step by using the MoO2Cl 2/Oxone system. Georg Thieme Verlag Stuttgart.
- Jeyakumar, Kandasamy,Chand, Dillip Kumar
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p. 807 - 819
(2008/09/21)
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- Pharmaceutical/cosmetic compositions comprising a novel RARbeta receptor-activating ligand
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Novel ligand compounds having the structural formula (I): and the salts and optical/geometrical isomers thereof are suited for formulation into pharmaceutical compositions useful in human or veterinary medicine, or, alternatively, into cosmetic compositio
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Page/Page column 4
(2008/06/13)
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- ADJUVANT IN THE FORM OF A LIPID-MODIFIED NUCLEIC ACID
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The present invention relates to an immune-stimulating adjuvant in the form of a lipid-modified nucleic acid, optionally in combination with further adjuvants. The invention relates further to a pharmaceutical composition and to a vaccine, each containing an immune-stimulating adjuvant according to the invention, at least one active ingredient and optionally a pharmaceutically acceptable carrier and/or further auxiliary substances and additives and/or further adjuvants. The present invention relates likewise to the use of the pharmaceutical composition according to the invention and of the vaccine according to the invention for the treatment of infectious diseases or cancer diseases. Likewise, the present invention includes the use of the immune-stimulating adjuvant according to the invention in the preparation of a pharmaceutical composition for the treatment of cancer diseases or infectious diseases.
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Page/Page column 20
(2010/11/29)
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- Synthesis of aminopropyl phosphonate nucleosides with purine and pyrimidine bases
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The synthesis and antiviral evaluation of new acyclic phosphonate nucleosides related to HPMPC (Cidofovir) has been described. These aminopropyl phosphonate nucleosides 1-3 have an amino function within either the acyclic chain (series 2 and 3) or as subs
- Zhou, Ding,Lagoja, Irene M.,Van Aerschot, Arthur,Herdewijn, Piet
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- Partial structures of ketoconazole as modulators of the large conductance calcium-activated potassium channel (BKCa)
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A series of partial structures of ketoconazole has been synthesized and tested for activity on the large conductance calcium-activated potassium channel (BK) in bovine smooth muscle cells. This has provided openers and blockers of the channel. The results suggest that the phenyl and phenoxy moieties are important for interaction with BK, whereas the imidazole group is unimportant. The properties of the phenoxy moiety seem to determine whether the compounds act to open or block the channel.
- Power, Eoin C.,Ganellin, C. Robin,Benton, David C.H.
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p. 887 - 890
(2007/10/03)
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- PROCESS FOR THE SYNTHESIS OF CATIONIC LIPIDS
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A process for the synthesis of lipid cations having general formula (6) in which: R1 represents a lipophilic chain; R2, R3, R4, which are identical or different from one another, represent C1-C10 alkyl, C1-C10 alkenyl, or C1-C10 alkynyl radicals, optionally containing hydroxyl, ether, halogen and acyloxy functions, and X- is an oxy-anion or a halide; in which a compound of formula (2) in which R5 and R6, which are identical or different from one another, represent a C1-C5 acyl, a benzyl group or a diolprotective group, is reacted in an alcoholic solvent with from 1 to 6 equivalents of NR2R3R4.
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Page/Page column 12-13
(2010/02/12)
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- NOVEL AMINOBENZOPHENONE COMPOUNDS
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The invention provides novel compounds according to formula I relates to compounds with the general formula I said compounds being useful, e.g. in the treatment of inflammatory, ophthalmic diseases or cancer.
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- Naphthyloxy acetic acid derivatives and a pharmaceutical composition comprising them as an active ingredient
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The naphthyloxyacetic acid derivatives of the formula (I) wherein A is H, -(alkylene)COOR1, -(alkylene)CONR2R3, -(alkylene)OH, -(alkylene)tetrazole, -(alkylene)CN; E is single bond or alkylene; G is —S—, —SO—, —SO2—, —O— or —NR4—; L is alkylene, —(CH2)m—CH═CH—(CH2)n— or —(CH2)x—CH(OH)—(CH2)y—; M is phenyl, phenyl(thio, oxy, amino), diphenylmethyl, diphenylmethyl(thio, oxy, amino), and pharmaceutical composition comprising them as an active ingradient. The compounds of the formula (I) can combine PGE2receptor and exhibit the activity to antagonize or agonize for PGE2receptor. Therefore, they are useful as anti-hyperlipemia, for the prevention of abortion, for analgesics, as antidiarrheals, sleep inducer, diuretic, anti-diabetes, abortient, cathartics, antiulcer, anti-gastritis or antihypertensive etc.
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Referential example 1
(2010/11/29)
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- Biphenyl derivatives substituted by an aromatic or heteroaromatic radical and pharamaceutical and cosmetic compositions containing same
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“Biphenyl derivatives substituted with an aromatic or heteroaromatic radical, and pharmaceutical and cosmetic compositions containing them” in which: Ar represents an aromatic or a heteroaromatic radical optionally substituted, in particular, with an alkyl or a carboxyl group, R2and R3represent, in particular, H or alkyl, or R2and R3, taken together, form a 5- or 6-membered ring, R4and R5represent, in particular, H or halogen, R6represents, in particular, H or lower alkyl, and the salts of the compounds of formula (I). These compounds can be used in particular in the treatment of dermatological complaints associated with a keratinization disorder, and for combating ageing of the skin.
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- Synthesis of oxazolidinones by a solid-phase/activation cycloelimination (sp/ace) methodology
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A versatile method for the solid-phase synthesis of oxazolidinones is described. An appropriate 1,2-diol is attached to immobilized sulfonyl chloride, resulting in the selective activation of one of the alcohol functions. The subsequent reaction of the ot
- Ten Holte, Peter,Van Esseveldt, Bart C. J.,Thijs, Lambertus,Zwanenburg, Binne
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p. 2965 - 2969
(2007/10/03)
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- Azulene derivatives
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The invention provides novel azulene derivatives of general formula I wherein R1 to R6 have the significance given in the description, as well as their tautomers, enantiomers, diastereomers, racemates and physiologically compatible salts or esters and substances which are hydrolyzed or metabolized in vivo to compounds of formula I. The invention is also concerned with a process and intermediates for the manufacture of the above compounds, pharmaceutical compositions which contain such compounds as well as the use of these compounds in the treatment of inflammatory conditions.
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- Synthesis and anti-hepatitis B virus activity of some 2,3-dihydroxyprop- 1-yl unnatural hetaryls
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The sodium salts of some hetaryls of the quinoxalin-2-ones 2-4, phthalazine-1,4-dione 5, phthalazin-1-one 6, and pyridazin-6-ones 7 and 8 were alkylated with (±) 2,3-0-isopropylidene-1-O-(4-toluenesulfonyl)glycerol (1) to give the respective tetraseco-nuc
- El Ashry, El Sayed H.,Abdel-Rahman, Adel A.-H.,Rashed, Nagwa,Rasheed, Hanaa A.
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p. 327 - 330
(2007/10/03)
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- Scavenger assisted combinatorial process for preparing libraries of tertiary amine compounds
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This invention relates to a novel solution phase process for the preparation of tertiary amine combinatorial libraries. These libraries have utility for drug discovery and are used to form wellplate components of novel assay kits.
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- Synthesis of acetal cationic lipids
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A series of positively charged lipids of the acetal type containing various cationic groups and a 1,3-dioxolane ring were synthesized.
- Klykov,Romanyuk,Serebrennikova
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p. 260 - 262
(2007/10/03)
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- Synthesis, antifungal activity and structure-activity relationships of 2-(alkyl or aryl)-2-(alkyl or polyazol-1-ylmethyl)-4-(polyazol-1-ylmethyl)- 1,3-dioxolanes
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A series of 2-(alkyl or aryl)-2-(alkyl or polyazol-1-ylmethyl)-4-(polyazol-1-ylmethyl)-1,3-dioxolanes Ia-u was synthesized and tested in vitro against pathogenic fungi in man, animals and plants: Candida albicans, Aspergillus flavus and Fusarium solani. Compounds Iq-t with two polyazol groups have an in vitro activity against these fungi with MIC (minimum inhibitory concentration) value of 5 μg mL-1.
- Baji,Kimny, Tan,Gasquez,Flammang,Compagnon,Delcourt,Mathieu,Viossat,Morgant,Nguyen-Huy
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p. 637 - 650
(2007/10/03)
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- Glyceryl-ether monooxygenase [EC 1.14.16.5], Part 9. Stereospecificity of the oxygenase reaction
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(2RS,1′R)-[1′-3H1]- and (2RS, 1′S)-[1′-3H1]-Hexadecyloxypropane-1,2-diols (chimyl alcohols) have been prepared and their stereochemistry has been confirmed by synthesizing the [2H1]-analogues using similar procedures. When they were used as substrates for glyceryl-ether monooxygenase from rat liver in the presence of oxygen and (RS)-6-methyl-5,6,7,8-tetrahydropterin as co-factor, the 1′S-isomer released 37% of its tritium into the aqueous buffer after 20 mins, whereas the 1′R-isomer released only 6.5% showing that the reaction was stereospecific for thepro-Hs hydrogen atom of the glyceryl ether substrate. This was in agreement with the kinetic parameters of unlabelled-(2RS)-3-, (2RS, 1′R)-3-[1′-2H1]-, (2RS, 1′S)-3-[1′-2H1]- and (2RS)-3-[1′,1′-2H 2]-hexadecyloxypropane-1,2-diols where the apparent Km values were about the same (49.4, 53.7, 49.3 and 54.0 μM respectively) but the apparent maximum velocities (Vmax in nmol min-1 mg-1 protein) of the first two substrates (37.5 and 37.5) were faster than for the latter two substrates (22.5 and 23.6), consistent with the pro-Hs hydrogen atom being replaced by the hydroxy group and a primary deuterium isotope effect of ~1.6.
- Taguchi, Hiroyasu,Paal, Bela,Armarego, Wilfred L. F.
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p. 303 - 307
(2007/10/03)
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- 37. Synthesis of highly fluorinated di-O-alk(en)yl-glycerophospholipids and evaluation of their biological tolerance
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The syntheses of various fluorocarbon/fiuorocarbon and fluorocarbon/hydrocarbon rac-1,2- and 1,3-di-O-alk(en)ylglycerophosphocholines and rac-1,2-di-O-alkylglycerophosphoethanolamines (see Fig.2), which may be used as components for drug-carrier and delivery systems, are described together with some results concerning their biological tolerance. They were obtained by phosphorylation of perfluoroalkylated rac-di-O-alk(en)ylglycerols using POCl3, then condensation with choline tosylate or N-Boc-ethanolamine (2-[(tert-butoxy)carbonyl-amino]ethanol) followed by Boc-deprotection (Schemes 6-8). The fluorocarbon/fluorocarbon 1,2-di-O-alkylglycerols were prepared by O-alkylation of rac-1-O-benzylglycerol using perfluoroalkylated mesylates, then hydrogenolysis for benzyl deprotection (Scheme I). The two different hydrophobic chains in the mixed fluorocarbon/ fluorocarbon and fluorocarbon/hydrocarbon 1,2-di-O-alk(en)ylglycerols were introduced starting from 1,2-O-isopropylidene- then O-trityl-protected glycerols or from 1,3-O-benzylidene-glycerol (Schemes 3 and 4). The perfluoroalkylated O-alkenylglycerols were obtained by O-alkylation of a glycerol derivative using an ω-unsaturated alkenyl reagent, the perfluoroalkyl segment being connected onto the double bond in a subsequent step (Schemes 1 and 3) The perfluoroalkylated symmetrical and mixed 1,3-di-O-alkylglycerols were synthesized by displacement of the Cl-atom in epichlorohydrin by perfluoroalkylated alcohols, then catalytic (SnCl4) opening of the oxirane ring of the resulting alkyl glycidyl ethers in neat alcohols (Scheme 5). When injected intravenously into mice, acute maximum tolerated doses higher than 1500 and 2000 mg/kg body weight were observed for the fluorinated glycerophosphocholines, indicating a very promising in vivo tolerance.
- Ravily, Veronique,Gaentzler, Sylvie,Santaella, Catherine,Vierling, Pierre
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p. 405 - 425
(2007/10/03)
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