- Mild and chemoselective lactone ring-opening with (TMS)ONa. Mechanistic studies and application to sweroside derivatives
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Mild and chemoselective opening of lactones with sodium trimethylsilanolate in high yields and aprotic solvents is described. Kinetic studies demonstrate that the BAc2 mechanistic pathway is followed. Nucleophilic attack of silanolate onto the carbonyl of the lactone moiety is the rate-determining step. NaOH present as an impurity accelerates the reaction. The method was further applied to the base-sensitive and stable lactones derived from highly functionalized iridoid derivatives.
- Lemoine, Hugues,Markovi?, Dean,Deguin, Brigitte
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Read Online
- Synthesis of AD-Dihydrodipyrrins Equipped with Latent Substituents of Native Chlorophylls and Bacteriochlorophylls
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Native chlorophylls and bacteriochlorophylls share a common trans-substituted pyrroline ring D (17-propionic acid, 18-methyl), whereas diversity occurs in ring A particularly at the 3-position. Two dihydrodipyrrins equipped with native-like D-ring substit
- Wang, Pengzhi,Lindsey, Jonathan S.
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p. 11794 - 11811
(2021/08/24)
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- Modified oligonucleotides and compound that can be used for synthesizing same
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The present disclosure falls within the field of biomedical technology, and in particular relates to modified oligonucleatides and a compound that can be used for synthesizing same and a method for modifying oligonucleotides. The present disclosure also relates to the use of the modified oligonucleotides for preventing and/or treating diseases associated with the liver in a subject.
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Paragraph 0135-0136
(2020/12/08)
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- POLYNUCLEOTIDE CONSTRUCTS
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Disclosed are polynucleotide constructs having a strand linked to a moiety carrying one or more auxiliary moieties. Also disclosed are polynucleotide constructs interrupted with a sugar analogue, and polynucleotide constructs with stereochemical^ enriched phosphorothioates. The polynucleotide constructs may be provided as hybridized polynucleotide constructs. Also featured are methods of delivery a polynucleotide construct to a cell and methods of reducing the expression of a protein in a cell by contacting the cell with the disclosed polynucleotide construct or hybridized polynucleotide construct.
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Page/Page column 93
(2018/03/09)
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- Synthesis of Thymoquinone-Artemisinin Hybrids: New Potent Antileukemia, Antiviral, and Antimalarial Agents
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A series of hybrid compounds based on the natural products artemisinin and thymoquinone was synthesized and investigated for their biological activity against the malaria parasite Plasmodium falciparum 3D7 strain, human cytomegalovirus (HCMV), and two leukemia cell lines (drug-sensitive CCRF-CEM and multidrug-resistant subline CEM/ADR5000). An unprecedented one-pot method of selective formation of C-10α-acetate 14 starting from a 1:1 mixture of C-10α- to C-10β-dihydroartemisinin was developed. The key step of this facile method is a mild decarboxylative activation of malonic acid mediated by DCC/DMAP. Ether-linked thymoquinone-artemisinin hybrids 6a/b stood out as the most active compounds in all categories, while showing no toxic side effects toward healthy human foreskin fibroblasts and thus being selective. They exhibited EC50 values of 0.2 μM against the doxorubicin-sensitive as well as the multidrug-resistant leukemia cells and therefore can be regarded as superior to doxorubicin. Moreover, they showed to be five times more active than the standard drug ganciclovir and nearly eight times more active than artesunic acid against HCMV. In addition, hybrids 6a/b possessed excellent antimalarial activity (EC50 = 5.9/3.7 nM), which was better than that of artesunic acid (EC50 = 8.2 nM) and chloroquine (EC50 = 9.8 nM). Overall, most of the presented thymoquinone-artemisinin-based hybrids exhibit an excellent and broad variety of biological activities (anticancer, antimalarial, and antiviral) combined with a low toxicity/high selectivity profile.
- Fr?hlich, Tony,Reiter, Christoph,Saeed, Mohamed E. M.,Hutterer, Corina,Hahn, Friedrich,Leidenberger, Maria,Friedrich, Oliver,Kappes, Barbara,Marschall, Manfred,Efferth, Thomas,Tsogoeva, Svetlana B.
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supporting information
p. 534 - 539
(2018/06/20)
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- Synthesis of Novel Hybrids of Thymoquinone and Artemisinin with High Activity and Selectivity Against Colon Cancer
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Colorectal cancer causes 0.5 million deaths each year. To combat this type of cancer the development of new specific drug candidates is urgently needed. In the present work seven novel thymoquinone–artemisinin hybrids with different linkers were synthesized and tested for their in vitro anticancer activity against a panel of various tumor cell lines. The thymoquinone–artesunic acid hybrid 7 a, in which both subunits are connected via an ester bond, was found to be the most active compound and selectively decreased the viability of colorectal cancer cells with an IC50value of 2.4 μm (HCT116) and 2.8 μm (HT29). Remarkably, hybrid 7 a was up to 20-fold more active than its parent compounds (thymoquinone and artesunic acid), while not affecting nonmalignant colon epithelial HCEC cells (IC50>100 μm). Moreover, the activity of hybrid 7 a was superior to that of various 1:1 mixtures of thymoquinone and artesunic acid. Furthermore, hybrid 7 a was even more potent against both colon cancer cell lines than the clinically used drug 5-fluorouracil. These results are another excellent proof of the hybridization concept and confirm that the type and length of the linker play a crucial role for the biological activity of a hybrid drug. Besides an increase in reactive oxygen species (ROS), elevated levels of the DNA-damage marker γ-H2AX were observed. Both effects seem to be involved in the molecular mechanism of action for hybrid 7 a in colorectal cancer cells.
- Fr?hlich, Tony,Ndreshkjana, Benardina,Muenzner, Julienne K.,Reiter, Christoph,Hofmeister, Elisabeth,Mederer, Sandra,Fatfat, Maamoun,El-Baba, Chirine,Gali-Muhtasib, Hala,Schneider-Stock, Regine,Tsogoeva, Svetlana B.
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supporting information
p. 226 - 234
(2017/02/15)
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- Lipase-mediated regioselective modifications of macrolactonic sophorolipids
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Chemoenzymatic synthesis and modification of well-defined macrolactonic sophorolipid (SLML) analogues via a series of successive regioselective de-esterification/transesterification reactions is investigated. Of the lipases screened, Candida antartica lip
- Sembayeva, Aliya,Berhane, Beniam,Carr, Jason A.
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p. 1873 - 1880
(2017/03/11)
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- POLYNUCLEOTIDE CONSTRUCTS HAVING AN AUXILIARY MOIETY NON-BIOREVERSIBLY LINKED TO AN INTERNUCLEOSIDE PHOSPHATE OR PHOSPHOROTHIOATE
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The invention features a hybridized polynucleotide construct including a passenger strand, a guide strand loadable into a RISC complex, and one or more auxiliary moieties. At least one of the auxiliary moieties is non-bioreversibly linked to an internucleoside phosphate or phosphorothioate in the passenger strand. The invention further features methods of delivery a polynucleotide construct to a cell and methods of reducing the expression of a protein in a cell. The methods typically involve contacting the cell with the hybridized polynucleotide construct.
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Page/Page column 60
(2017/07/15)
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- MONONUCLEOTIDES HAVING A BIOREVERSIBLE DISULFIDE GROUP
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The invention features a mononucleotide comprising a nucleobase bonded to a sugar having a 3'-carbon and a 5'-carbon, where the 5'-carbon is bonded to a phosphorus (V) atom of a phosphate group through an oxygen atom, the phosphorus (V) atom being bonded to (i) a disulfide bioreversible group through an oxygen atom; and (ii) (a) optionally substituted amino, optionally substituted alkoxy, optionally substituted aryloxy, or optionally substituted heteroaryloxy; or (b) the 3'-carbon through an oxygen atom. The invention also features methods of delivering the mononucleotide to a cell and methods of treating a subject having Hepatitis C.
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Page/Page column 52
(2016/07/05)
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- POLYNUCLEOTIDE CONSTRUCTS HAVING DISULFIDE GROUPS
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The invention features polynucleotide constructs containing one or more components (i) containing a disulfide linkage, where each of the one or more components is attached to an internudeotide bridging group or a terminal group of the polynucleotide construct, and each of the one or more components (i) contains one or more bulky groups proximal to the disulfide group. The invention also features polynucleotide constructs containing one or more components (i) containing a disulfide linkage, where each of the one or more components (i) is attached to an internudeotide bridging group or a terminal group of the polynucleotide construct, and each of the one or more components (i) contains at least 4 atoms in a chain between the disulfide linkage and the phosphorus atom of the internudeotide bridging group or the terminal group; and where the chain does not contain a phosphate, an amide, an ester, or an alkenylene. The invention also features methods of delivering a polynucleotide to a cell using the polynucleotide constructs of the invention.
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Page/Page column 157
(2015/05/26)
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- POLYNUCLEOTIDE CONSTRUCTS HAVING BIOREVERSIBLE AND NON-BIOREVERSIBLE GROUPS
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The invention features a hybridized polynucleotide construct containing a passenger strand, a guide strand loadable into a RISC complex, and (i) a 3'-terminal or an internucleotide non-bioreversible group in the guide strand; or (ii) a 5'-terminal, a 3'-terminal, or an internucleotide non-bioreversible group in the passenger strand, and a 5'-terminal, a 3'-terminal, or an internucleotide disulfide bioreversible group in the guide strand or the passenger strand. The invention also features methods of delivering a polynucleotide to a cell using the hybridized polynucleotide construct. The invention further features methods of reducing the expression of a polypeptide in a cell using the hybridized polynucleotide construct.
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Page/Page column 157; 158
(2016/02/19)
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- PRODUCTION OF FUEL FROM CHEMICALS DERIVED FROM BIOMASS
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Hydrocarbons may be formed from six carbon sugars. This process involves obtaining a quantity of a hexose sugar. The hexose sugar may be derived from biomass. The hexose sugar is reacted to form an alkali metal levulinate, an alkali metal valerate, an alkali metal 5-hydroxy pentanoate, or an alkali metal 5-alkoxy pentanoate. An anolyte is then prepared for use in a electrolytic cell. The anolyte contains the alkali metal levulinate, the alkali metal valerate, the alkali metal 5-hydroxy pentanoate, or the alkali metal 5-alkoxy pentanoate. The anolyte is then decarboxylated. This decarboxylating operates to decarboxylate the alkali metal levulinate, the alkali metal valerate, the alkali metal 5-hydroxy pentanoate, or the alkali metal 5-alkoxy pentanoate to form radicals, wherein the radicals react to form a hydrocarbon fuel compound.
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Page/Page column Sheet 7
(2012/05/21)
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- Cyclodextrin-Initiated polymerization of cyclic esters in bulk: Formation of polyester-tethered cyclodextrins
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Cyclodextrins were found to initiate ring-opening polymerization of some cyclic esters selectively to give a polyester with a CD at the chain end. Copyright
- Takashima, Yoshinori,Osaki, Motofumi,Harada, Akira
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p. 13588 - 13589
(2007/10/03)
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- Acridinium compound having a plurality of luminescent groups and binding groups, and conjugate thereof
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Acridinium compounds and their conjugates exhibiting high chemiluminescence yield are provided. Such compounds may be used to enable a highly sensitive specific binding assay. The acridinium compounds are represented by formula (I): wherein A is a linker;
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- Cyclic renin inhibitors
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Compounds of the formula: are disclosed. These compounds inhibit the angiotensinogen-cleaving action of the natural proteolytic enzyme, renin, and are useful in treating, preventing or managing renin-associated hypertension, hyperaldosteronism, congestive
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- Design and synthesis of P2-P1'-linked macrocyclic human renin inhibitors
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Using a computer model of the active site of human renin developed at Merck, we designed a series of novel P2-P1'-linked, macrocyclic renin inhibitors 3-10. These unique inhibitors incorporate a transition-state isostere within a 13- or 14-membered ring. The three most active compounds in this family were 13-membered-ring glutamine-derived inhibitor 3, 14-membered-ring diaminopropionic acid derived inhibitor 6, and 13-membered-ring diol 9 (IC50 0.61, 0.59, 0.65 μM, respectively). Modification of inhibitor 3 at P4 led to 56 nM macrocyclic renin inhibitor 39. This study shows the viability of renin inhibitor designs which incorporate a scissile-bond replacement within a macrocycle.
- Weber,Halgren,Doyle,Lynch,Siegl,Parsons,Greenlee,Patchett
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p. 2692 - 2701
(2007/10/02)
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- Macrocyclic lactones having renin inhibiting properties
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Compounds of the formula:
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