- New amphiphilic polycarbonates with side functionalized cholesteryl groups as biomesogenic units: synthesis, structure and liquid crystal behavior
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The synthesis of four new amphipathic copolymers with side functionalized-cholesterol based aliphatic polycarbonates is described through the ring-opening polymerization and coupling reaction. The chemical structures, liquid crystal (LC) behavior, and thermal stability of the chiral monomers and copolymers obtained in this study were characterized using Fourier transform infrared (FT-IR) spectroscopy, proton nuclear magnetic resonance (1H NMR) spectroscopy, gel permeation chromatography (GPC), polarizing optical microscopy (POM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and thermogravimetric analysis (TGA) measurements. The effect of the spacer length on the molecular interaction and mesophase of the chiral monomers and copolymers was investigated. It was found that chiral monomers with longer spacer seemed beneficial for the formation of mesophases, and the additional ordering on polymerization caused mesophases to be more ordered than for the corresponding monomers. The LC copolymers all revealed a smectic A phase with an interdigitated molecular arrangement. The results seemed to show a decreased tendency toward the glass transition temperature, and isotropic temperature for the LC copolymers by increasing the spacer length. In addition, four LC copolymers had a good thermal stability.
- Xu, Xiaoxu,Liu, Xiaofeng,Li, Qun,Hu, Jianshe,Chen, Qifan,Yang, Liqun,Lu, Yanhua
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p. 14176 - 14185
(2017/03/11)
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- BIPOLAR TETRAETHER LIPIDS
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Disclosed herein, inter alia, are compounds, compositions, and liposomes and methods of thereof.
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Paragraph 0028; 0530
(2017/03/21)
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- TYK2 INHIBITORS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same for the inhibition of TYK2, and the treatment of TYK2-mediated disorders.
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Paragraph 00874
(2017/03/21)
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- Synthesis and evaluation of symmetric acyclic nucleoside bisphosphonates as inhibitors of the Plasmodium falciparum, Plasmodium vivax and human 6-oxopurine phosphoribosyltransferases and the antimalarial activity of their prodrugs
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Two new series of symmetric acyclic nucleoside bisphosphonates (ANbPs) have been synthesised as potential inhibitors of the Plasmodium falciparum (Pf) and vivax (Pv) 6-oxopurine phosphoribosyltransferases. The structural variability between these symmetric ANbPs lies in the number of atoms in the two acyclic linkers connecting the N9 atom of the purine base to each of two phosphonate groups and the branching point of the acyclic moiety relative to the purine base, which occurs at either the alpha or beta positions. Within each series, six different 6-oxopurine bases have been attached. In general, the ANbPs with either guanine or hypoxanthine have lower Ki values than for those containing either the 8-bromo or 7-deaza 6-oxopurine bases. The lowest Ki values obtained for the two parasite enzymes were 0.1?μM (Pf) and 0.2?μM (Pv) for this series of compounds. Two phosphoramidate prodrugs of these inhibitors exhibited antimalarial activity against Pf in infected erythrocyte cell culture with IC50 values of 0.8 and 1.5?μM. These two compounds exhibited low cytotoxicity in human A549 cells having CC50 values of >300?μM resulting in an excellent selectivity index.
- ?pa?ek, Petr,Keough, Dianne T.,Chavchich, Marina,Dra?ínsky, Martin,Janeba, Zlatko,Naesens, Lieve,Edstein, Michael D.,Guddat, Luke W.,Hocková, Dana
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p. 4008 - 4030
(2017/07/05)
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- 3-hydroxyl oxygen heterocyclic butane preparation method of compound
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The invention discloses a synthetic method of a 3-hydroxy oxetane compound shown as a formula I. The method provided by the invention employs substituted glycerol I-1 as a raw material, which is subjected to condensation with aldehydes and ketones compounds to obtain a compound I-2; the I-2 is subjected to R2 protection to obtain a compound I-3; the compound I-3 is subjected to removal of aldehydes and ketones protecting groups to obtain a compound I-4; the compound I-4 is subjected to intramolecular cyclization to obtain a compound I-5; and the compound I-5 is subjected to removal of R2 protection to obtain a target compound I. Although the method has a long route, the reaction conditions are mild, and the post treatment and detection are convenient; therefore, the method is suitable for industrialized production.
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Paragraph 0032; 0035; 0036
(2016/10/07)
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- Effect of Headgroups on Small-Ion Permeability across Archaea-Inspired Tetraether Lipid Membranes
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This paper examines the effects of four different polar headgroups on small-ion membrane permeability from liposomes comprised of Archaea-inspired glycerolmonoalkyl glycerol tetraether (GMGT) lipids. We found that the membrane-leakage rate across GMGT lipid membranes varied by a factor of ≤1.6 as a function of headgroup structure. However, the leakage rates of small ions across membranes comprised of commercial bilayer-forming 1-palmitoyl-2-oleoyl-sn-glycerol (PO) lipids varied by as much as 32-fold within the same series of headgroups. These results demonstrate that membrane leakage from GMGT lipids is less influenced by headgroup structure, making it possible to tailor the structure of the polar headgroups on GMGT lipids while retaining predictable leakage properties of membranes comprised of these tethered lipids. Extremophiles require robust membranes with low ion permeability to survive in harsh conditions. These Archaea organisms achieve low membrane permeability, in part, by generating lipids with unusual structural features such as tethering of their lipid tails. A systematic study probing the effect of polar headgroups in synthetic Archaea-inspired lipids showed little dependence of membrane leakage rates of small ions as a function of headgroup structure.
- Koyanagi, Takaoki,Leriche, Geoffray,Yep, Alvin,Onofrei, David,Holland, Gregory P.,Mayer, Michael,Yang, Jerry
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supporting information
p. 8074 - 8077
(2016/06/14)
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- HIV PROTEASE INHIBITORS AND METHODS FOR USING
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Compounds that inhibit proteolytic enzymes of Human Immunodeficiency Virus (HIV) are described. Preparation of the inhibitors, pharmaceutical compositions containing them, and uses of the compounds or compositions for the treatment of HIV infections are also described.
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Page/Page column 26-27
(2011/06/10)
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- ANTIOXIDANT POLYMERS CONTAINING [1,2]-DITHIOLANE MOIETIES AND USES THEREOF
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The present invention describes polymers containing 1,2-dithiolanes capable of acting as scavengers of free radicals, metals and reactive oxygen species. Also described are methods of synthesizing the antioxidant 1,2-dithiolane derivatives and polymerization thereof to produce biodegradable antioxidant polymers. The antioxidant polymers of the present invention may be used to treat diseases or conditions caused by oxidative stress and other free radical mediated conditions. The antioxidant polymers may also be used for the preparation of antioxidant particulate delivery devices of therapeutic agents.
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Page/Page column 57-58
(2008/12/07)
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- Flexible cyclic ethers/polyethers as novel P2-ligands for HIV-1 protease inhibitors: Design, synthesis, biological evaluation, and protein-ligand X-ray studies
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We report the design, synthesis, and biological evaluation of a series of novel HIV-1 protease inhibitors. The inhibitors incorporate stereochemically defined flexible cyclic ethers/polyethers as high affinity P2-ligands. Inhibitors containing small ring 1,3-dioxacycloalkanes have shown potent enzyme inhibitory and antiviral activity. Inhibitors 3d and 3h are the most active inhibitors. Inhibitor 3d maintains excellent potency against a variety of multi-PI-resistant clinical strains. Our structure-activity studies indicate that the ring size, stereochemistry, and position of oxygens are important for the observed activity. Optically active synthesis of 1,3-dioxepan-5-ol along with the syntheses of various cyclic ether and polyether ligands have been described. A protein-ligand X-ray crystal structure of 3d-bound HIV-1 protease was determined. The structure revealed that the P2-ligand makes extensive interactions including hydrogen bonding with the protease backbone in the S2-site. In addition, the P2-ligand in 3d forms a unique water-mediated interaction with the NH of Gly-48.
- Ghosh, Aran K.,Gemma, Sandra,Baldridge, Abigail,Wang, Yuan-Fang,Kovalevsky, Andrey Yu.,Koh, Yashiro,Weber, Irene T.,Mitsuya, Hiroaki
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experimental part
p. 6021 - 6033
(2009/10/23)
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- Bifunctional acyclic nucleoside phosphonates. 1. Symmetrical 1,3-bis[(phosphonomethoxy)propan-2-yl] derivatives of purines and pyrimidines
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We report here a general method for the synthesis of new symmetrical bis-phosphonates of acyclic nucleosides. 1,3-Bis[(diisopropoxyphosphoryl) methoxy] derivatives of purine and pyrimidine bases were prepared by their reaction with 1,3-bis[(diisopropoxyphosphoryl)-methoxy]propan-2-yl tosylate. Cytosine, uracil and thymine provided regiospecifically N1-isomers. This alkylation regiospecificity applies to several other tosylates of primary and secondary alcohols as well. 6-Chloropurine and 2-amino-6-chloropurine were alkylated in N9 position. Resulting bis-phosphonates were converted to the respective free phosphonic acids and tested for antiviral and cytostatic activity. Despite the fact that no biological activity was found so far, the outcome of this work can serve as a useful tool in synthesis of novel groups of acyclic nucleoside phosphonates (ANPs).
- Vrbovska, Silvie,Holy, Antonin,Pohl, Radek,Masojidkova, Milena
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p. 543 - 566
(2007/10/03)
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- Polycarbonate and poly(carbonate-ester)s synthesized from biocompatible building blocks of glycerol and lactic acid
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The synthesis and characterization of a polycarbonate of glycerol and poly(carbonate-ester)s of glycerol and L-lactic acid are reported. These new polymers possess a hydrolyzable backbone, tunable hydrophobic/hydrophilic properties, and functionalizable p
- Ray III, William C.,Grinstaff, Mark W.
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p. 3557 - 3562
(2007/10/03)
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- Antihypertensive phosphate derivatives
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Antihypertensive phosphate derivatives having the following formula are described: STR1 wherein X is a C1 -C24 branched or straight chain alkyl group; R is selected from the group consisting of hydrogen and C1 -C4 alkyl, with the proviso that at least one R group is not hydrogen; T is selected from the group consisting of hydrogen and STR2 wherein R1 is selected from the group consisting of hydrogen, C1 -C4 branched or straight chain alkyl, C1 -C4 branched or straight chain alkoxy and C1 -C4 branched or straight chain alkylamino; Q is a bivalent radical selected from the group consisting of --(CH2)p -- and --(CHR1)p --, wherein p is an integer from 2 to 12 and the moiety --(CHR1)p -- represents an alkylene chain which is substituted by one or more C1 -C10 alkyl groups or phenyl groups; Z is selected from the group consisting of STR3 wherein R2 may be chain alkyl and q is an integer from 4 to 7; in either the racemic or in the optically active form.
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- STEREOCONTROLLED SYNTHESIS OF A TRANS-ANTI-TRANS TRICYCLE VIA A TRANSANNULAR DIELS-ALDER STRATEGY.
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Transannular Diels-Alder reaction of trans-cis-cis macrocyclic triene 20 yields trans-syn-cis tricycle 21 which is converted into trans-anti-trans tricycle 24 by epimerization at C9 after appropriate functional group transformation.
- Marinier, Anne,Deslongchamps, Pieere
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p. 6215 - 6218
(2007/10/02)
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- Phosphocholine derivatives having antihypertensive action
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Phosphocholine derivatives and compositions are described which are useful as hypotensive agents and in the treatment of hypertension in warm-blooded animals.
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- NEW POTENTIAL IMMUNOENHANCING COMPOUNDS. II. SYNTHESES OF 1-DEOXY-1-THIOPHOSPHATIDYLCHOLINE DERIVATIVES
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The syntheses of four 1-deoxy-1-thiophosphatidylcholine derivatives are described.
- Nali, Micaela,Rindone, Bruno,Bosone, Enrico,Farina, Paolo,Innocenti, Sergio,Valcavi, Umberto
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- Facile synthesis of platelet-activating factor and racemic analogues containing unsaturation in the sn-1-alkyl chain
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Platelet-activating factor, (PAF, 1-O-hexadecyl-2-acetyl-sn-glycero-3-phophocholine), and octadecyl-PAF were synthesized chemically as the racemates. The sn-1-O-alkyl isomers were isolated after treatment of the racemates with phospholipase A2 and subsequent reacetylation of the 1-O-alkyl-2-lyso-sn-glycero-3-phosphocholines released. Analogues of PAF containing unsaturated alkyl moieties at the sn-1 position were synthesized by utilizing the methoxyethoxymethyl protecting group as a novel method for preparing unsaturated alkyl lipids. This procedure provides a facile means for preparing unsaturated ether phospholipids of defined structure that may be tritiated to high radiospecific activity for metabolic studies. Unsaturation in the alkyl chain had minimal effect on the bioactivities examined in this study.
- Surles,Wykle,O'Flaherty,Salzer,Thomas,Snyder,Piantadosi
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