86520-52-7Relevant articles and documents
Sequential synthesis of a new analogue of amlodipine bearing a short amino polyethyleneglycol chain
Legeay, Jean Christophe,Vanden Eynde, Jean Jacques,Bazureau, Jean Pierre
, p. 12081 - 12086 (2007)
3-Ethyl 5-methyl 2-[(2-(2-(2-aminoethoxy)ethoxy)ethoxy)methyl]-4-(2-chlorophenyl)-6-methy l-1,4-dihydropyridine-3,5-dicarboxylate as new analogue of amlodipine was prepared in five steps with an overall yield of 22%. The 1,4-dihydropyridine nucleus was built in two steps via Knoevenagel reaction and the amino group of this analogue has been prepared in good yield by Staudinger reduction of the azido 1,4-dihydropyridine precursor in the last step.
Pentavalent Sialic Acid Conjugates Block Coxsackievirus A24 Variant and Human Adenovirus Type 37-Viruses That Cause Highly Contagious Eye Infections
Johansson, Emil,Caraballo, Rémi,Mistry, Nitesh,Zocher, Georg,Qian, Weixing,Andersson, C. David,Hurdiss, Daniel L.,Chandra, Naresh,Thompson, Rebecca,Fr?ngsmyr, Lars,Stehle, Thilo,Arnberg, Niklas,Elofsson, Mikael
, p. 2683 - 2691 (2020)
Coxsackievirus A24 variant (CVA24v) and human adenovirus 37 (HAdV-37) are leading causative agents of the severe and highly contagious ocular infections acute hemorrhagic conjunctivitis and epidemic keratoconjunctivitis, respectively. Currently, neither vaccines nor antiviral agents are available for treating these diseases, which affect millions of individuals worldwide. CVA24v and HAdV-37 utilize sialic acid as attachment receptors facilitating entry into host cells. Previously, we and others have shown that derivatives based on sialic acid are effective in preventing HAdV-37 binding and infection of cells. Here, we designed and synthesized novel pentavalent sialic acid conjugates and studied their inhibitory effect against CVA24v and HAdV-37 binding and infection of human corneal epithelial cells. The pentavalent conjugates are the first reported inhibitors of CVA24v infection and proved efficient in blocking HAdV-37 binding. Taken together, the pentavalent conjugates presented here form a basis for the development of general inhibitors of these highly contagious ocular pathogens.
Click chemistry oligomerisation of azido-alkyne-functionalised galactose accesses triazole-linked linear oligomers and macrocycles that inhibit Trypanosoma cruzi macrophage invasion
Campo, Vanessa L.,Ivanova, Irina M.,Carvalho, Ivone,Lopes, Carla D.,Carneiro, Zumira A.,Saalbach, Gerhard,Schenkman, Sergio,Da Silva, Jo?o Santana,Nepogodiev, Sergey A.,Field, Robert A.
, p. 7334 - 7353 (2015)
Abstract Reaction of 2-(2-(2-azidoethoxy)ethoxy)ethyl 6-O-(prop-2-ynyl)-β-d-galactopyranoside (7) under CuAAC conditions gives rise to mixed cyclic and linear triazole-linked oligomers, with individual compounds up to d.p. 5 isolable, along with mixed larger oligomers. The linear compounds resolve en bloc from the cyclic materials by RP HPLC, but are separable by gel permeation chromatography. The triazole-linked oligomers - pseudo-galactooligomers - were demonstrated to be acceptor substrates for the multi-copy cell surface trans-sialidase of the human parasite Trypanosoma cruzi. In addition, these multivalent TcTS ligands were able to block macrophage invasion by T. cruzi.
Hybrid triazolium and ammonium ions-contained hyperbranched polymer with enhanced ionic conductivity
Li, Hongfei,Wang, Cuifang,Liao, Xiaojuan,Xie, Meiran,Sun, Ruyi
, p. 297 - 305 (2017)
Hyperbranched poly(triazole) with tertiary amine moiety and longer flexible polyethylene glycol (PEG) terminal group (hb-PTA-PEG) was synthesized by successive Cu(I)-catalyzed azide-alkyne cycloaddition polymerization, and the corresponding hyperbranched poly(triazolium)s containing hybrid quaternary ammonium ion, [hb-PTA-PEG]+[I]? and [hb-PTA-PEG]+[TFSI]?, were obtained after N-alkylation and anion exchange reactions. These hyperbranched polymers presented broad electrochemical stability window of above 6.0 V versus Ag+/Ag and 5.3 V versus Li+/Li, and displayed low glass transition temperature in the range of ?13 to ?37 °C, owing to the hyperbranched structure combined with the hybrid ionic moiety and longer flexible PEG end-group. The ionic [hb-PTA-PEG]+[TFSI]? showed superior ionic conductivity, which was above 10?5 S cm?1 at 30 °C.
Development of a microfluidic "click chip" incorporating an immobilized Cu(i) catalyst
Li, Hairong,Whittenberg, Joseph J.,Zhou, Haiying,Ranganathan, David,Desai, Amit V.,Koziol, Jan,Zeng, Dexing,Kenis, Paul J. A.,Reichert, David E.
, p. 6142 - 6150 (2015)
We have developed a microfluidic "click chip" incorporating an immobilized Cu(i) catalyst for click reactions. The microfluidic device was fabricated from polydimethylsiloxane (PDMS) bonded to glass and featured ～14400 posts on the surface to improve catalyst immobilization. This design increased the immobilization efficiency and reduces the reagents' diffusion time to an active catalyst site. The device also incorporates five reservoirs to increase the reaction volume with minimal hydrodynamic pressure drop across the device. A novel water-soluble Tris-(benzyltriazolylmethyl)amine (TBTA) derivative capable of stabilizing Cu(i), ligand 2, was synthesized and successfully immobilized on the chip surface. The catalyst immobilized chip surface was characterized by X-ray photoelectron spectroscopy (XPS). The immobilization efficiency was evaluated via radiotracer methods: the immobilized Cu(i) was measured as 1136 ± 272 nmol and the surface immobilized Cu(i) density was 81 ± 20 nmol cm-2. The active Cu(i)-ligand 2 could be regenerated up to five times without losing any catalyst efficiency. The "click" reaction of Flu568-azide and propargylamine was studied on chip for proof-of-principle. The on-chip reaction yields were ca. 82% with a 50 min reaction time or ca. 55% with a 15 min period at 37 °C, which was higher than those obtained in the conventional reaction. The on-chip "click" reaction involving a biomolecule, cyclo(RGDfK) peptide was also studied and demonstrated a conversion yield of ca. 98%. These encouraging results show promise on the application of the Cu(i) catalyst immobilized "click chip" for the development of biomolecule based imaging agents. This journal is
Peptide-targeted dendrimeric prodrugs of 5-aminolevulinic acid: A novel approach towards enhanced accumulation of protoporphyrin IX for photodynamic therapy
Tewari,Dondi,Yaghini,Pourzand,MacRobert,Eggleston
supporting information, (2021/02/26)
Photodynamic therapy (PDT) is a promising approach for the targeted treatment of cancer and various other human disorders. An effective, clinically approved approach in PDT involves the administration of 5-aminolevulinic acid (ALA) to generate elevated levels of the natural photosensitiser protoporphyrin IX (PpIX). The development of prodrugs of ALA is of considerable interest as a means to enhance the efficiency and cell selectivity of PpIX accumulation for PDT applications. In this work a novel peptide-targeted dendrimeric prodrug of 5-aminolevulinic acid (ALA) 13 was synthesised which displays nine copies of ALA on a core structure that is linked to a homing peptide for targeted delivery to a specific cancer cell type. The synthesis was accomplished effectively via a flexible, modular solid phase and solution phase route, using a combination of solid phase peptide synthesis and copper-catalysed azide-alkyne cycloaddition chemistry. The prodrug system shows a sustained and enhanced production of protoporphyrin IX (PpIX) in the MDA-MB-231 cell line that over-expresses the epidernal growth factor receptor (EGFR+) in comparison to equimolar ALA and the corresponding non-targeted ALA dendrimer (nine copies of ALA). This study provides a proof of concept for the development of a new generation of prodrugs for ALA-based photodynamic therapy that can deliver an enhanced ALA payload to specific tissue types.
Targeting Colorectal Cancer with Conjugates of a Glucose Transporter Inhibitor and 5-Fluorouracil
Chang, Chun-Kai,Chiu, Pei-Fang,Yang, Hui-Yi,Juang, Yu-Pu,Lai, Yen-Hsun,Lin, Tzung-Sheng,Hsu, Lih-Ching,Yu, Linda Chia-Hui,Liang, Pi-Hui
supporting information, p. 4450 - 4461 (2021/05/06)
Overexpression of glucose transporters (GLUTs) in colorectal cancer cells is associated with 5-fluorouracil (1, 5-FU) resistance and poor clinical outcomes. We designed and synthesized a novel GLUT-targeting drug conjugate, triggered by glutathione in the tumor microenvironment, that releases 5-FU and GLUTs inhibitor (phlorizin (2) and phloretin (3)). Using an orthotopic colorectal cancer mice model, we showed that the conjugate exhibited better antitumor efficacy than 5-FU, with much lower exposure of 5-FU during treatment and without significant side effects. Our study establishes a GLUT-targeting theranostic incorporating a disulfide linker between the targeting module and cytotoxic payload as a potential antitumor therapy.
