80322-82-3Relevant articles and documents
Tetrahydroisoquinoline derivative as well as preparation method and medical application thereof
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Paragraph 0209; 0215; 0389-0394, (2021/04/21)
The invention relates to a tetrahydroisoquinoline derivative, a preparation method thereof and medical application of the tetrahydroisoquinoline derivative. Specifically, the invention relates to a tetrahydroisoquinoline derivative as shown in a general formula (I) and a medicinal salt thereof, a preparation method of the tetrahydroisoquinoline derivative and the medicinal salt thereof, and application of the tetrahydroisoquinoline derivative and the medicinal salt thereof as NHE3 inhibitors, particularly as a therapeutic agent for diseases related to body fluid retention or salt overload or gastrointestinal diseases. Wherein the definition of each substituent in the general formula (I) is the same as the definition in the specification.
BIODEGRADABLE COMPOUND, LIPID PARTICLE, COMPOSITION COMPRISING LIPID PARTICLE, AND KIT
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Paragraph 0096; 0139-0140, (2020/09/09)
The present embodiment provides a compound represented by the formula (1): [in-line-formulae]Q-CHR2??(1)[/in-line-formulae] (Q is a nitrogen-containing aliphatic group containing two or more tertiary nitrogens but no oxygen, and R is an aliphatic group containing a biodegradable group). From the compound in combination with other lipids such as a lipid capable of reducing aggregation, lipid particles can be formed. Further, the compound can be used for a pharmaceutical composition to deliver an activator into cells.
DIMER COMPOUNDS, AND USE IN BINDING TOXIC REPEATS OF RNA
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Paragraph 0233; 0234, (2020/07/16)
Provided herein are compounds and methods for modulating abnormal repeat expansions of gene sequences. More particularly, provided are dimeric inhibitors of RNA and the uses of such inhibitors in regulating nucleotide repeat expansions, e.g., to treat Myotonic Dystrophy Type 1 (DM1), Myotonic Dystrophy Type 2 (DM2), Fuchs dystrophy, Huntington Disease, Amyotrophic Lateral Sclerosis, or Frontotemporal Dementia.
Synthesis of peptide homo- and heterodimers as potential mimics of platelet-derived growth factor BB
Stubbing, Louise A.,Kaur, Harveen,Feng, Sheryl X.,Aalderink, Miranda,Dragunow, Michael,Brimble, Margaret A.
, (2020/07/28)
Pericyte loss is correlated with blood-brain barrier leakage in neurological disorders such as Alzheimer's disease. The platelet-derived growth factor receptor β (PDGFRβ)/platelet-derived growth factor BB (PDGF-BB) signalling pathway is key to the regulation of pericyte survival and proliferation. A series of peptide dimers mimicking the ligand PDGF-BB were prepared in the hope of stimulating PDGFRβ internalisation and activation of this pathway. Copper-catalysed azide-alkyne cycloaddition of peptide monomers with PEGylated linkers of varying length afforded the desired peptide dimers. Evaluation of the peptide dimers in human brain pericyte assays revealed no effect on PDGFRβ internalisation nor cell proliferation at concentrations 10 μM. The peptide dimers also did not act as antagonists at PDGFRβ at concentrations 10 μM.
Probing the Existence of a Metastable Binding Site at the β2-Adrenergic Receptor with Homobivalent Bitopic Ligands
Gaiser, Birgit I.,Danielsen, Mia,Marcher-R?rsted, Emil,R?pke J?rgensen, Kira,Wróbel, Tomasz M.,Frykman, Mikael,Johansson, Henrik,Br?uner-Osborne, Hans,Gloriam, David E.,Mathiesen, Jesper Mosolff,Sejer Pedersen, Daniel
, p. 7806 - 7839 (2019/09/07)
Herein, we report the development of bitopic ligands aimed at targeting the orthosteric binding site (OBS) and a metastable binding site (MBS) within the same receptor unit. Previous molecular dynamics studies on ligand binding to the β2-adrenergic receptor (β2AR) suggested that ligands pause at transient, less-conserved MBSs. We envisioned that MBSs can be regarded as allosteric binding sites and targeted by homobivalent bitopic ligands linking two identical pharmacophores. Such ligands were designed based on docking of the antagonist (S)-alprenolol into the OBS and an MBS and synthesized. Pharmacological characterization revealed ligands with similar potency and affinity, slightly increased β2/β1AR-selectivity, and/or substantially slower β2AR off-rates compared to (S)-alprenolol. Truncated bitopic ligands suggested the major contribution of the metastable pharmacophore to be a hydrophobic interaction with the β2AR, while the linkers alone decreased the potency of the orthosteric fragment. Altogether, the study underlines the potential of targeting MBSs for improving the pharmacological profiles of ligands.
Freestanding flexible polymer films based on bridging of two EDOT units with functionalized chains for use in long-term-stable supercapacitors
Ye, Guo,Zhou, Qianjie,Li, Danqin,Zuo, Yinxiu,Duan, Xuemin,Zhou, Weiqiang,Xu, Jingkun
, p. 4824 - 4834 (2018/04/02)
Freestanding flexible capacitive materials are ideal for use in bendable electronic devices. However, it is difficult to prepare pure PEDOT films in a freestanding state by chemical and electrochemical methods. Here, we used a simple strategy of introducing alkoxy, ether, ester, and amide chains for bridging two EDOT units to form precursors, which could then be electrodeposited readily to produce freestanding and flexible films. The precursor with the amide group was suitable for obtaining higher-quality films with improved thermal stability, mechanical properties, and capacitive performance. In addition, the asymmetric PBEDTA//PEDOT capacitors exhibited a capacitance retention rate of 98.5% after 5000 cycles, which is higher than those of PBEDTH//PEDOT (92.7%), PBEDTG//PEDOT (80.5%), and PBEDTE//PEDOT (86.8%) capacitors. This result indicates that the polymer films and, in particular, the PBEDTA films, are suitable for use in flexible supercapacitors.
OPIOID RECEPTOR ANTAGONIST CONJUGATE AND USE THEREOF
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Paragraph 0072, (2018/12/07)
The present invention relates to an opioid receptor antagonist conjugate and a use thereof. In particular, the present invention relates to a covalent coupling conjugate of a hydrophilic polymer and an opioid receptor antagonist and the use thereof.
LOW MOLECULAR WEIGHT POLYETHYLENE GLYCOL DRUG CONJUGATES HAVING IMPROVED DRUG BIOLOGICAL ACTIVITY
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Paragraph 0048, (2016/04/19)
Provided are polyethylene glycol drug conjugates of general formula (I), (II) or (III) and pharmaceutical compositions and a use thereof. The conjugates are formed by combining low molecular weight polyethylene glycol with 2-4 drug molecules. The conjugates can interact with receptor dimers or polymers, thereby improving the in vivo distribution of the drug, changing the oil and water distribution coefficient, enhancing the pharmacological activity, reducing the blood-brain barrier permeability of the drug, and improving the bioavailability of the drug.
Grafting of polymeric platforms on gold by combining the diazonium salt chemistry and the photoiniferter method
Ahmad, Randa,Mocaer, Adrien,Gam-Derouich, Sarra,Lamouri, Aazdine,Lecoq, Hélène,Decorse, Philippe,Brunet, Philippe,Mangeney, Claire
, p. 12 - 20 (2015/02/02)
The grafting of stable and strongly attached polymeric platforms on gold is a key factor for successful applications in biology, catalysis and sensing. Here, we report on the use of a combination of the iniferter method and the diazonium salt chemistry for preparing smart polymeric platforms attached through covalent bonds on gold. For this, bifunctional molecules bearing aryl diazonium coupling agents for anchoring on gold and N,N-diethyldithiocarbamate groups for initiating the growth of polymer chains were used. These two moieties were separated by oligo(ethylene oxide) spacers of various lengths allowing a fine tuning of the hydrophilic properties of the grafted photoinitiator layers. Cross-linked copolymers of methacrylic acid (MAA) and N,N′-methylenebisacrylamide (MBAm) were then grown from the gold surfaces under UV light. The polymer films were characterized in terms of chemical composition and wettability by X-ray photoelectron spectroscopy and contact angle measurements, respectively. The grafting procedure was simple, rapid and effective in producing polymer-grafted Au surfaces at room temperature. The diethyldithiocarbamil groups remaining at the end of the growing tethered chains could then be easily exchanged by a UV-light induced radical-exchange experiment in order to obtain terminal amino moieties able to immobilize citrate-capped gold nanoparticles, through electrostatic interactions. The results obtained in the present work highlight the efficiency of the diazonium salt chemistry coupled to the photo-iniferter based surface grafting approach to spontaneously functionalize gold surfaces through covalent bonds. This strategy open new opportunities for the preparation of "smart" hybrid platforms made of pH-responsive polymers and nanoparticle assemblies.
Esterification of carboxylic acids with alkyl halides using imidazolium based dicationic ionic liquids containing bis-trifluoromethane sulfonimide anions at room temperature
Jadhav, Arvind H.,Lee, Kyuyoung,Koo, Sangho,Seo, Jeong Gil
, p. 26197 - 26208 (2015/10/20)
Task-specific room temperature ionic liquids (RTILs) composed of symmetrical N-methylimidazolium rings linked with a short oligo (ethylene glycol) chain (cationic part) and bis-trifluoromethane sulfonimide (NTf2, anionic part) were successfully synthesized, and their physicochemical properties were determined by various modern analytical techniques. The catalytic activity of the synthesized RTILs was evaluated in the esterification reaction of acids with alkyl halides in solvent-free conditions at room temperature. From the screening test, all the synthesized RTILs showed a high yield with significant selectivity for respective esters in a very short reaction time. Especially, 0.1 equimolar of RTIL-1 ([tetraEG(mim)2][NTf2]2) was found to be, the most efficient and reusable catalyst for this reaction. As a result, 100% conversion and up to a 94% yield of the respective ester product was obtained in a 30 min reaction time. This might be due to their synergetic effect of Lewis acidity, wide liquid range, and high miscibility compared to the other homogeneous and heterogeneous catalysts. Beside this, RTIL was easily separated from the reaction mixture and reused several times without any significant loss of catalytic activity and structural property. The present dicationic ionic liquids (ILs) under a solvent-free catalytic system were found to be kinetically fast, naturally benign, and achieved good yields for esterification of carboxylic acids with alkyl halides.