DOCSLIB.ORG

Synthesis and Characterization of Thermoplastic

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Synthesis and Characterization of Thermoplastic SYNTHESIS AND CHARACTERIZATION OF THERMOPLASTIC POLYPHENOXYQUINOXALINES A Dissertation Presented to The Graduate Faculty of the University of Akron In Partial Fulfillment of the Requirement for the Degree Doctor of Philosophy Haci Bayram Erdem May, 2008 © 2008 HACI BAYRAM ERDEM ALL RIGHTS RESERVED SYNTHESIS AND CHARACTERIZATION OF THERMOPLASTIC POLYPHENOXYQUINOXALINES Haci Bayram Erdem Dissertation Approved: Accepted: ______________________________ _____________________________ Advisor Department Chair Frank W. Harris Mark D. Foster ______________________________ _____________________________ Committee Member Dean of the College Stephen Z. D. Cheng Stephen Z. D. Cheng ______________________________ _____________________________ Committee Member Dean of the Graduate School Judit Puskas George R. Newkome ______________________________ _____________________________ Committee Member Date Roderic P. Quirk ______________________________ Committee Member David A. Modarelli ii ABSTRACT This research was divided into two main parts. In the first part, a new facile route to relatively inexpensive thermoplastic polyphenoxyquinoxalines was developed. The synthetic route involves the aromatic nucleophilic substitution reaction of bisphenols with 2,3-dichloroquinoxaline. The dichloro monomer was prepared in two steps. In the first step, oxalic acid was condensed with o-phenylenediamine to give 2,3- dihydroxyquinoxaline. In the second step, 2,3-dihydroxyquinoxaline was treated with thionyl chloride to give 2,3-dichloroquinoxaline. This monomer was successfully polymerized with bisphenol-A, bisphenol-S, hexafluorobisphenol-A and 9,9-bis(4- hydroxyphenyl)fluorenone. Hydroquinone and biphenol, however, can not be polymerized to high molecular weight polymers because of the premature precipitation of crystalline oligomers. The glass transition temperatures of the high molecular weight polymers prepared from a series of bisphenols range from 191 °C to 279 °C, and their thermal decomposition temperatures are around 500 °C. The polymers are soluble in a wide range of solvents and can be solution-cast into thin films that are colorless and transparent. The polymers have tensile strengths ranging from 61 to 107 MPa, and tensile moduli ranging from 3.5 to 2.3 GPa. The synthesis of polymer obtained from 2,3- dichloroquinoxaline and bisphenol-A was scaled up to afford 500 g of material. This polymer is a thermoplastic with a melt-viscosity less than 1000 Pa.s. at 300 °C. The notched Izod impact strength of injection-molded samples of this polymer is 40.7 J/m. iii In the second part of this research, the synthetic method has been modified to allow the preparation of quinoxaline containing polyimides. Thus, 2,3- dichloroquinoxaline was treated either with p-nitrophenol followed by reduction of nitro groups, or with p-aminophenols to directly obtain the desired 2,3-(4- aminophenoxy)quinoxaline. This diamine was polymerized with 3,3’,4,4’- biphenyldianhydride, 4,4’-oxydiphthalic anhydride and 2,2’-bis(3,4- dicarboxyphenyl)hexafluoropropane dianhydride. The polymerizations were carried out by the two step method. The poly(amic acid) intermediates were thermally imidized. Although they have high molecular weights judged by their inherent viscosities ranging from 0.51 to 1.01, thin films of all these polyimides were brittle. The glass transition temperatures of the polyimides range from 259 °C to 282 °C with thermal decomposition temperatures around 550 °C. The polyimide obtained from 2,3-(4- aminophenoxy)quinoxaline and 3,3’,4,4’-biphenyldianhydride was found to be semi- crystalline. iv ACKNOWLEDGEMENTS I would like to thank to my advisor Dr. Frank W. Harris for his support, guidance and especially his patience. It is an honor for me being his last Ph. D. student. I would also thank to my committee members, Dr. Judit E. Puskas (Chairman), Dr. Roderic P. Quirk, Dr. David A. Modarelli and Dr. Stephen Z. D. Cheng for their numerous corrections and suggestions. In addition, I would like to thank Dr. Brian Knapp for being my first trainer in Harris’ Group. It is him that I owe most my laboratory skills. I would also like to thank Dr. Dong Zhong and Dr. Limin Sun for being my next tutors. I gratefully acknowledge Dr. John D. Harvey for his help in the preparation of this thesis. Finally, I thank my parents, Sukru and Emine Erdem. It is them that I dedicate this dissertation. v TABLE OF CONTENTS Page LIST OF TABLES…………………………………………………….…………………..x LIST OF FIGURES……………………………………………………………………....xi LIST OF SCHEMES………………………….………………………………………...xiii CHAPTER I. INTRODUCTION………………………………………………………………………1 II. HISTORICAL BACKGROUND…………………………………………………...….3 2.1 High Temperature/High Performance Polymers…………………………………...3 2.2 Synthesis of Polyquinoxalines (PQs) and Polyphenylquinoxalines (PPQs)………..4 2.2.1 Quinoxalines…………………………………………………………………...4 2.2.2 Polyquinoxalines (PQs) …………………………………………………….…5 2.2.3 Polyphenylquinoxalines(PPQs)………………………………………………..5 2.2.4 Properties of PQs and PPQs……………………………………………………6 2.2.4.1 Isomerism in PQs and PPQs………………………………………………7 2.2.4.2 Thermal Properties of PQs and PPQs……………………………………..8 2.3 Synthesis of Polyarylethers by Aromatic Nucleophilic Substitution Reaction…...10 2.3.1 Aromatic Nucleophilic Substitution Reactions……………………………....10 2.3.2 Development of Polymerizations by Aromatic Nucleophilic Substitution Reactions………………………………………………………………………....12 2.3.2.1. Strong Base vs. Weak Base Process in Polymerizations by SNAr……....17 vi 2.3.2.2 Reductive Dehalogenation Reactions……………………………………19 2.3.2.3 Cyclization in the Synthesis of Polysulfones……………………..…….21 2.3.3. Synthesis of Polyaryletherketones…………………………………………..23 2.3.4 Synthesis of Polyaryletherimides…………………………………………….24 2.3.5 Synthesis of Polyarylsulfides………………………………………………...26 2.3.6 Synthesis of Poly(aryletherphenyl quinoxalines) by SNAr Reaction………...27 2.4 Polyimides………………………………………………………………………...34 2.4.1 Synthesis of Polyimides……………………………………………………...34 2.4.1.1 Introduction………………………………………………………….…..34 2.4.1.2 Two-Step Method………………………………………………………..35 2.4.1.2.1 Thermal Imidization………………………………………………...37 2.4.1.2.2 Chemical Imidization………………………………………………..39 2.4.1.3 One-Step Method………………………………………………………...41 2.3.1.4 Synthesis of Polyimides by Transimidization…………………………...42 2.4.3 Poly (imide-aryl ether quinoxalines)………………………………………....43 2.4.4 Poly (ether imide)s Having Ortho-Linked Aromatic Units in the Main Chain.......................................................................................................................46 III.EXPERIMENTAL……………………………………………………...…………….50 3.1. Chemical Instrumentation………………………………………………………...50 3.2 Reagents and Solvents………………………………………………………...…..52 3.2.1 Reagents………………………………………………………………………52 3.2.2 Solvents…………………………………………………………………..…..53 3.3 Synthesis of Small Molecules……………………………………………………..54 vii 3.3.1 2,3-Dihydroxyquinoxaline (76a)……………………………………...……………54 3.3.2 2,3-Dichloroquinoxaline (75)…………………………………………..…….54 3.3.3 2,3-Diphenoxyquinoxaline (79)…………………………………………...….55 3.3.4 2,3-Bis(4-aminophenoxy)quinoxaline (94a)………………………………….55 3.3.5 2,3-Bis(4-nitrophenoxy)quinoxaline (97a)………………………………..….56 3.3.6 12H-Quinoxalino[2,3-b][1,4]benzoxazine (98)……………………………....57 3.3.7 2,3-Bis(2-aminophenoxy)quinoxaline (97b)……………………………….…58 3.3.8 2,3-Bis(2-nitrophenoxy)quinoxaline (94b)……………………………..…….58 3.4 Synthesis of Polymers (Macromolecules)………………………………………...59 3.4.1 Synthesis of Polyphenoxyquinoxalines……………………………………....59 3.4.1.1 Polymerization of 2,3-Dichloroquinoxaline with Bisphenol-A Using 100 % Excess Potassium Carbonate…………………………………....59 3.4.1.2 Polymerization of 2,3-Dichloroquinoxaline with Bisphenol-A Using 25 % Excess Potassium Carbonate…………………………………..…60 3.4.1.3 Polymerization of 2,3-Dichloroquinoxaline with 9,9’-Bis(4-hydroxyphenyl)fluorene…...………………………………………61 3.4.1.4 Polymerization of 2,3-Dichloroquinoxaline with Bisphenol-S……...…..62 3.4.1.5 Polymerization of 2,3-Dichloroquinoxaline with Hexafluorobisphenol-A………………………………………………………..63 3.4.1.6 Polymerization of 2,3-Dichloroquinoxaline with Hydroquinone…….….63 3.4.1.7 Polymerization of 2,3-Dichloroquinoxaline with Biphenol……………...64 3.4.1.8 Polymerization of 2,3-Dichloroquinoxaline with Bisphenol-A (50 %) and Hydroquinone (50 %)………………………………65 3.4.1.9 Polymerization of 2,3-Dichloroquinoxaline with Bisphenol-A (50 %) and Biphenol (50 %)……………………………….……66 3.4.2 General Procedure for the Synthesis of Polyimides………………………….66 viii 3.5 General Procedure for the Preparation of Thin Films for Tensile Testing………..67 3.6 General Procedure for the Sample Preparation Using Injection Molding………...67 IV. RESULTS AND DISCUSSION……………………………………………………..68 4.1 Synthesis and Characterization of Polyphenoxyquinoxalines…………………….68 4.1.1 Introduction…………………………………………………………………...68 4.1.2 Synthesis of 2,3-Dichloroquinoxaline………………………………………..69 4.1.3 Model Reaction with 2,3-Dichloroquinoxaline…………………..…………..74 4.1.4 Optimization of Polymerization Conditions…………………………….……76 4.1.5 Synthesis of Polyphenoxyquinoxalines……………………………….….…..85 4.1.6 Thermal Properties of Polyphenoxyquinoxalines……………………….…....90 4.1.7 Solubilities of the Polyphenoxyquinoxalines…………………………………92 4.1.8 Optical Properties of Polyphenoxyquinoxalines……………………….……..93 4.1.9 Tensile Properties of Polyphenoxyquinoxalines……………………………...97 4.1.10 Melt Processability of Polyphenoxyquinoxaline 85………..……………....99 4.1.11. Tensile Properties of Injection Molded Samples of 85 …...…………………....100 4.1.12. Impact Properties of Injection Molded Samples of 85……..……………..102 4.2 Poly(imide-aryl
Load more

Recommended publications
  • Electrochemical and Quantum Chemical Studies on Corrosion Inhibition Performance Of
    Materials Research. 2020; 23(2): e20180610 DOI: https://doi.org/10.1590/1980-5373-MR-2018-0610 Electrochemical and Quantum Chemical Studies on Corrosion Inhibition Performance of 2,2’-(2-Hydroxyethylimino)bis[N-(alphaalpha-dimethylphenethyl)-N-methylacetamide] on Mild Steel Corrosion in 1M HCl Solution Iman Danaeea* , S. RameshKumarb, M. RashvandAveic, M. Vijayand aPetroleum University of Technology, Abadan Faculty of Petroleum Engineering, Abadan, Iran bSri Vasavi College, Department of Chemistry, Erode, Tamilnadu-638 316, India. cK. N. Toosi University of Technology, Department of chemistry, Tehran, Iran dCentral Electrochemical Research Institute, Centre for Conducting Polymers, Electrochemical Materials Science Division, Karikudi, 630006, India Received: September 7, 2018; Revised: January 13, 2020; Accepted: March 16, 2020 The inhibitory effect of Oxethazaine drug, 2,2’-(2-Hydroxyethylimino)bis[N-(alphaalpha- dimethylphenethyl)-N-methylacetamide] on corrosion of mild steel in 1M HCl solution was studied by weight loss measurements, electrochemical impedance spectroscopy and potentiodynamic polarization methods. The results of gravimetric and electrochemical methods demonstrated that the inhibition efficiency increased with an increase in inhibitor concentration in 1M HCl solution. The results from electrochemical impedance spectroscopy proved that the inhibition action of this drug was due to adsorption on the metal surface. Potentiodynamic polarization studies revealed that the molecule was a mixed type inhibitor. The adsorption of the molecule on the metal surface was found to obey Langmuir Adsorption isotherm. Potential of zero charge at the metal-solution interface was measured to provide the inhibition mechanism. The temperature dependence of the corrosion rate was also studied in the temperature range from 30 to 50 °C. Quantum chemical calculations were applied to correlate electronic structure parameters of the drug with its inhibition performance.
    [Show full text]
  • Durham E-Theses
    Durham E-Theses Molecular pharmacology of a Novel NR2B-selective NMDA Receptor Antagonist Bradford, Andrea Marie How to cite: Bradford, Andrea Marie (2006) Molecular pharmacology of a Novel NR2B-selective NMDA Receptor Antagonist, Durham theses, Durham University. Available at Durham E-Theses Online: http://etheses.dur.ac.uk/2736/ Use policy The full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-prot purposes provided that: • a full bibliographic reference is made to the original source • a link is made to the metadata record in Durham E-Theses • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders. Please consult the full Durham E-Theses policy for further details. Academic Support Oce, Durham University, University Oce, Old Elvet, Durham DH1 3HP e-mail: [email protected] Tel: +44 0191 334 6107 http://etheses.dur.ac.uk 2 Molecular Pharmacology of a Novel NR2B-รelective NMDA Receptor Antagonist PhD Thesis The copyright of this thesis rests with the author or ¿he university to which it was submitted. No quotation from it, or ๒fonnation derived from it may be published without the prior written consent of the author or university, and any information derived from it should be acknowledged. Andrea Marie Bradford School of Biological & Вю^ Sciences University of Durham Supervisor: Dr Paul Chazot October 2006 7 JUM 200? Abstract The NMDA receptor is a heteromeric ligand-gated ion channel in the central nervous system (CNS).
    [Show full text]
  • Octahydroquinoxalin-2 (1H)-One-Based Aminophosphonic
    materials Article Octahydroquinoxalin-2(1H)-One-Based Aminophosphonic Acids and Their Derivatives—Biological Activity towards Cancer Cells Jakub Iwanejko 1 , El˙zbietaWojaczy ´nska 1,* , Eliza Turlej 2 , Magdalena Maciejewska 2 and Joanna Wietrzyk 2 1 Faculty of Chemistry, Wrocław University of Science and Technology, Wybrze˙zeWyspia´nskiego 27, 50-370 Wrocław, Poland; [email protected] 2 Department of Experimental Oncology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wrocław, Poland; [email protected] (E.T.); [email protected] (M.M.); [email protected] (J.W.) * Correspondence: [email protected]; Tel.: +48-71-320-2410 Received: 19 March 2020; Accepted: 19 May 2020; Published: 22 May 2020 Abstract: In the search for new antitumor agents, aminophosphonic acids and their derivatives based on octahydroquinoxalin-2(1H)-one scaffold were obtained and their cytotoxic properties and a mechanism of action were evaluated. Phosphonic acid and phosphonate moieties increased the antiproliferative activity in comparison to phenolic Mannich bases previously reported. Most of the obtained compounds revealed a strong antiproliferative effect against leukemia cell line (MV-4-11) with simultaneous low cytotoxicity against normal cell line (mouse fibroblasts-BALB/3T3). The most active compound was diphenyl-[(1R,6R)-3-oxo-2,5-diazabicyclo[4.4.0]dec-4-yl]phosphonate. Preliminary evaluation of the mechanism of action showed the proapoptotic effect associated with caspase 3/7 induction. Keywords: aminophosphonate; imine; antiproliferative activity; cell cycle; mitochondrial membrane potential 1. Introduction At present, our attention is focused on the COVID-19 pandemic and there is a tendency to neglect the civilization diseases which however remain the main reason for mortality worldwide.
    [Show full text]
  • Improving Thermodynamic Consistency Among Vapor Pressure, Heat of Vaporization, and Liquid and Ideal Gas Heat Capacities Joseph Wallace Hogge Brigham Young University
    Brigham Young University BYU ScholarsArchive All Theses and Dissertations 2017-12-01 Improving Thermodynamic Consistency Among Vapor Pressure, Heat of Vaporization, and Liquid and Ideal Gas Heat Capacities Joseph Wallace Hogge Brigham Young University Follow this and additional works at: https://scholarsarchive.byu.edu/etd Part of the Chemical Engineering Commons BYU ScholarsArchive Citation Hogge, Joseph Wallace, "Improving Thermodynamic Consistency Among Vapor Pressure, Heat of Vaporization, and Liquid and Ideal Gas Heat Capacities" (2017). All Theses and Dissertations. 6634. https://scholarsarchive.byu.edu/etd/6634 This Dissertation is brought to you for free and open access by BYU ScholarsArchive. It has been accepted for inclusion in All Theses and Dissertations by an authorized administrator of BYU ScholarsArchive. For more information, please contact [email protected], [email protected]. Improving Thermodynamic Consistency Among Vapor Pressure, Heat of Vaporization, and Liquid and Ideal Gas Heat Capacities Joseph Wallace Hogge A dissertation submitted to the faculty of Brigham Young University In partial fulfillment of the requirements for the degree of Doctor of Philosophy W. Vincent Wilding, Chair Thomas A. Knotts Dean Wheeler Thomas H. Fletcher John D. Hedengren Department of Chemical Engineering Brigham Young University Copyright © 2017 Joseph Wallace Hogge All Rights Reserved ABSTRACT Improving Thermodynamic Consistency Among Vapor Pressure, Heat of Vaporization, and Liquid and Ideal Gas Heat Capacity Joseph Wallace Hogge Department of Chemical Engineering, BYU Doctor of Philosophy Vapor pressure ( ), heat of vaporization ( ), liquid heat capacity ( ), and ideal gas heat capacity ( ) are important properties for process design and optimization. This work vap Δvap focuses on improving the thermodynamic consistency and accuracy of the aforementioned properties since these can drastically affect the reliability, safety, and profitability of chemical processes.
    [Show full text]
  • |||||||III US005514680A United States Patent (19) 11 Patent Number: 5,514,680 Weber Et Al
    |||||||III US005514680A United States Patent (19) 11 Patent Number: 5,514,680 Weber et al. (45) Date of Patent: May 7, 1996 54 GLYCINE RECEPTOR ANTAGONISTS AND 0377112 7/1990 European Pat. Off.. THE USE THEREOF 0511152 10/1992 European Pat. Off.. 572852 12/1993 European Pat. Off.. 2451049 4/1976 Germany. (75) Inventors: Eckard Weber, Laguna Beach, Calif.; 2446543 4/1976 Germany. John F. W. Keana, Eugene, Oreg. 2847285 5/1980 Germany. 72674 11/1974 Poland. 73) Assignees: State of Oregon, acting by and WO91/13878 9/1991 WIPO. through The Oregon State Board of WO92/07847 11/1991 WIPO. Higher Education, acting for and on WO92/O2487 2/1992 WIPO. behalf of The Oregon Health Sciences WO92/11012 7/1992 WIPO. University and The University of WO92/11245 7/1992 WIPO. Oregon, Eugene, Oreg.; The Regents WO92/14740 9/1992 WIPO : of the University of California, WO92/15565 9/1992 WIPO. Oakland, Calif. 94.07500 4/1994 WIPO. OTHER PUBLICATIONS (21) Appl. No.: 148,259. Allison et al., Polyfluoroheterocyclic Compounds, Part XX. 22 Filed: Nov. 5, 1993 Preparation and Nucleophilic Substitution of Hexafluoro quinoxaline, J. Fluorine Chem. 1:59-667 (1971). Related U.S. Application Data Burton et al., Halogeno-o-phenylenediamines and Derived Heterocycles. Part I. Reductive Fission of Benzotriazoles to 63 Continuation-in-part of PCT/US93/05859, Jun. 17, 1993, o-Phenylenediamines, J. Chem. Soc. (C) 10:1268-1273 which is a continuation-in-part of Ser. No. 69,274, May 28, (1968). 1993, abandoned, which is a continuation-in-part of Ser. No. Lutfy et al., Blockade of Morphine Tolerance by 995,167, Dec.
    [Show full text]
  • Synthesis and Cytotoxic Evaluation of Some Novel Quinoxalinedione Diarylamide Sorafenib Analogues
    Research in Pharmaceutical Sciences, April 2018; 13(2): 168-176 School of Pharmacy & Pharmaceutical Sciences Received:September 2017 Isfahan University of Medical Sciences Accepted: January 2018 Original Article Synthesis and cytotoxic evaluation of some novel quinoxalinedione diarylamide sorafenib analogues Mojtaba Khandan, Sedighe Sadeghian-Rizi, Ghadamali Khodarahmi, and Farshid Hassanzadeh* Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Science, Isfahan University of Medical Sciences, Isfahan, I.R. Iran Abstract A series of novel sorafenib analogues containing a quinoxalinedione ring and amide linker were synthesized. A total of 9 novel compounds in 6 synthetic steps were synthesized. Briefly, the amino group of p-aminophenol was first protected which then followed by O-arylation with 5-chloro-2-nitroaniline to provide compound d. Reduction of the nitro group of compound d and cyclization of the diamine group of compound e with oxalic acid afforded compound f which on deacetylation yeilded compound g. Then compound g was reacted with different acyl halides to afford the target compounds 1h-1p. Chemical structures of synthesized compounds were confirmed by 1H NMR and FT-IR analysis. All compounds were evaluated at 1, 10, 50 and 100 μM concentrations for their cytotoxicity against HeLa and MCF-7 cancer cell lines. Some of the compounds showed good cytotoxic activity, especially compounds 1i and 1k-1n with the IC50 values of 19, 16, 22, 18, and 16 µM against MCF-7 cell line and 20, 18, 25, 20, and 18 µM against HeLa cell line, respectively. Keywords: Cytotoxicity; Sorafenib; Quinoxalinedione; Amide INTRODUCTION cancer types such as metastatic colorectal, brain, leukemia, breast, glioblastoma, Cancer, one of the most serious illnesses, advanced gastric, cervical, thyroid, non-small considered the second leading cause of death cell lung cancer, prostate, bladder and worldwide after cardiovascular diseases.
    [Show full text]
  • Imidazole-Substituted Quinoxalinedione Derivatives
    s\ — Illl INI II II III lllll I Mil II I II OJII Eur°Pean Patent Office <*S Office europeen des brevets (11) EP 0 919 554 A1 (12) EUROPEAN PATENT APPLICATION published in accordance with Art. 158(3) EPC (43) Date of publication: (51) Int. CI.6: C07D 403/04, C07D 403/12, 02.06.1999 Bulletin 1999/22 A61K 31/495 (21) Application number: 97925284.8 v ' ^ (86)/0~x International application number:u PCT/JP97/01905 (22) Date of filing: 05.06.1997 (87) International publication number: WO 97/46555 (1 1 .1 2.1 997 Gazette 1 997/53) (84) Designated Contracting States: • OHMORI, Junya AT BE CH DE DK ES Fl FR GB GR IE IT LI LU NL Tsukuba-shi, Ibaraki 305 (JP) PTSE • SHISHIKURA, Jun-ichi Tsukuba-shi, Ibaraki 305 (JP) (30) Priority: 06.06.1996 JP 144282/96 • OKADA, Masamichi Tsukuba-shi, Ibaraki 305 (JP) (71) Applicant: . SASAMATA Masao YAMANOUCHI PHARMACEUTICAL CO., LTD. Tsukuba-gu'n, Ibaraki 300-24 (JP) Tokyo 103 (JP) (74) Representative: (72) Inventors: Geering, Keith Edwin • SAKAMOTO, Shuichi REDDIE & GROSE Ushiku-shi, Ibaraki 300-1 2 (JP) ! 6 Theobalds Road London WC1X8PL(GB) (54) IMIDAZOLE-SUBSTITUTED QUINOXALINEDIONE DERIVATIVES (57) Imidazole-substituted quinoxalinedione deriva- R1 is a triazolyl group, tives the formula represented by following general (I) or R2: a hydrogen atom, a nitro group, a halogeno- salts thereof and pharmaceutically acceptable pharma- lower alkyl group, a cyano group, an amino group, a ceutical useful compositions as glutamate receptor mono- or di-lower alkylamino group or a halogen antagonists and the like, which comprise said com- atom, salts thereof and pounds or pharmaceutically accepta- Pi3 and Pi4: may be the same or different from each ble carriers.
    [Show full text]
  • Oxford Handbooks Online (
    AMPA and Kainate Receptors AMPA and Kainate Receptors G. Brent Dawe, Patricia M. G. E. Brown, and Derek Bowie The Oxford Handbook of Neuronal Ion Channels Edited by Arin Bhattacharjee Subject: Neuroscience, Molecular and Cellular Systems Online Publication Date: Oct 2020 DOI: 10.1093/oxfordhb/9780190669164.013.8 Abstract and Keywords α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate-type gluta­ mate receptors (AMPARs and KARs) are dynamic ion channel proteins that govern neu­ ronal excitation and signal transduction in the mammalian brain. The four AMPAR and five KAR subunits can heteromerize with other subfamily members to create several com­ binations of tetrameric channels with unique physiological and pharmacological proper­ ties. While both receptor classes are noted for their rapid, millisecond-scale channel gat­ ing in response to agonist binding, the intricate structural rearrangements underlying their function have only recently been elucidated. This chapter begins with a review of AMPAR and KAR nomenclature, topology, and rules of assembly. Subsequently, receptor gating properties are outlined for both single-channel and synaptic contexts. The struc­ tural biology of AMPAR and KAR proteins is also discussed at length, with particular fo­ cus on the ligand-binding domain, where allosteric regulation and alternative splicing work together to dictate gating behavior. Toward the end of the chapter there is an overview of several classes of auxiliary subunits, notably transmembrane AMPAR regula­ tory proteins and Neto proteins, which enhance native AMPAR and KAR expression and channel gating, respectively. Whether bringing an ion channel novice up to speed with glutamate receptor theory and terminology or providing a refresher for more seasoned biophysicists, there is much to appreciate in this summation of work from the glutamate receptor field.
    [Show full text]
  • Addis Ababa University School of Graduate Studies
    ADDIS ABABA UNIVERSITY SCHOOL OF GRADUATE STUDIES STUDIES ON METAL COMPLEXES DERIVED FROM PHYSIOLOGICALLY ACTIVE QUINOXALINE DERIVATIVES GRADUATE PROJECT CHEM. 774 BY GOJJE GAMO JULY 2006 STUDIES ON METAL COMPLEXES DERIVED FROM PHYSIOLOGICALLY ACTIVE QUINOXALINE DERIVATIVES Graduate Project Chem.774 Submitted to the School of Graduate Studies Addis Ababa University In Partial Fulfillment of the Requirements for the Degree of Master of Science in Chemistry By Gojje Gamo July 2006 ADDIS ABABA UNIVERSITY SCHOOL OF GRADUATE STUDIES STUDIES ON METAL COMPLEXES DERIVED FROM PHYSIOLOGICALLY ACTIVE QUINOXALINE DERIVATIVES GRADUATE PROJECT CHEM.774 BY GOJJE GAMO DEPARTMENT OF CHEMISTRY FACULTY OF SCIENCE Approved by the examining board: 1. Prof. V.J.T. Raju _________________ ___________________ Name Signature Date 2. Dr. Yonas Chebude _________________ ___________________ Name Signature Date DECLARATION I hereby declare that this project is my original work and has not been presented for a degree in any other university. I have cited and referenced all materials and results that are not original to this work. All materials and sources used for this project have been dully acknowledged. Name: Gojje Gamo Signature: ______________________ Place and date of submission: Department of Chemistry Addis Ababa University July 2006 This project has been submitted for examination with our approval as university advisors. Prof. V.J.T. Raju______________________________________ Dr. Yonas Chebude___________________________________ 1 TO MY WIFE, CHILDREN AND OUR PARENTS i ACKNOWLEDGEMENTS I would like to express my sincere feelings of gratitude and appreciation to my advisors Prof. Nigussie Retta, Prof. V.J.T. Raju and Dr. Yonas Chebude for their day-to-day follow up, supply of reference materials, valuable suggestions, advices, guidances, encouragement, and in general helping me in all aspects needed during the whole work of this project.
    [Show full text]
  • Quantitative Physiological Characterization of a Quinoxalinedione Non-NMDA Receptor Antagonist
    The Journal of Neuroscience, September 1969, g(9): 32303236 Quantitative Physiological Characterization of a Quinoxalinedione non-NMDA Receptor Antagonist Kelvin A. Yamada, Janet M. Dubinsky, and Steven M. Rothman Departments of Anatomy and Neurobiology and of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110 The effects of 6-cyano-7-nitroquinoxaline-2,34ione (CNQX, tors in physiological events has been hampered by the lack of or FG 9065) on excitatory amino acid responses in cultured potent, selective antagonists for these receptors. The blockers neurons from rat hippocampus were studied using tight-seal now used to antagonize KA and QA, usually y-D-glutamylgly- whole-cell recording techniques. CNQX reduced the mag- tine (Francis et al., 1980) or kynurenic acid (Robinson et al., nitude of peak inward currents produced by exogenously 1984) are relatively weak and are actually more potent against applied kainate, quisqualate, and N-methyl-D-aspartate NMDA responses. It is likely that many events triggered by (NMDA) with K,‘s of 2.5, 3.5, and 96 PM, respectively. The activation of KA or QA receptors in some preparations are not antagonism was competitive against kainate and quisqual- significantly reduced by these antagonists because of their low ate, but noncompetitive against NMDA. Glycine markedly potency. reduced CNQX antagonism of NMDA responses. The same Honor6 and colleagues (Drejer and Honor&, 1988; Honor& et recording technique using pairs of monosynaptically con- al., 1988) have recently described 2 quinoxalinediones, which nected neurons demonstrated reversible diminution of ex- potently block many KA and QA responses. These compounds, citatory postsynaptic potentials in 7 of 7 pairs, using CNQX 6,7-dinitroquinoxaline-2,3-dione (DNQX, or FG 9041) and at concentrations as low as 10 PM.
    [Show full text]
  • New Use of Glutamate Antagonists for the Treatment of Cancer
    Europäisches Patentamt (19) European Patent Office Office européen des brevets (11) EP 1 002 535 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int. Cl.7: A61K 31/435, A61K 31/55, 24.05.2000 Bulletin 2000/21 A61K 31/495 (21) Application number: 98250380.7 (22) Date of filing: 28.10.1998 (84) Designated Contracting States: (71) Applicant: AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU Ikonomidou, Hrissanthi MC NL PT SE 13505 Berlin (DE) Designated Extension States: AL LT LV MK RO SI (72) Inventor: Ikonomidou, Hrissanthi 13505 Berlin (DE) (54) New use of glutamate antagonists for the treatment of cancer (57) New therapies can be devised based upon a are likely to be useful in treating cancer and can be for- demonstration of the role of glutamate in the pathogen- mulated as pharmaceutical compositions. They can be esis of cancer. Inhibitors of the interaction of glutamate identified by appropriate screens. with the AMPA, kainate, or NMDA receptor complexes EP 1 002 535 A1 Printed by Xerox (UK) Business Services 2.16.7 (HRS)/3.6 12EP 1 002 535 A1 Description system, seizures and hypoglycemia. In addition, gluta- mate is thought to be involved in the pathogenesis of [0001] Glutamate is a major neurotransmitter but chronic neurodegenerative disorders, such as amyo- possesses also a wide metabolic function in the body. It trophic lateral sclerosis, Huntington's, Alzheimer's and is released from approximately 40% of synaptic termi- 5Parkinson's disease. Functional glutamate receptors nals and mediates many physiological functions by acti- have been also identified in lung, muscle, pancreas and vation of different receptor types (Watkins and Evans bone (Mason DJ, Suva LJ, Genever PG, Patton AJ, (1981) Excitatory amino acid transmitters, Annu.
    [Show full text]
  • Crystal Structures of the Glur2 Ligand Binding Core
    Neuron, Vol. 28, 165±181, October, 2000, Copyright 2000 by Cell Press Mechanisms for Activation and Antagonism of an AMPA-Sensitive Glutamate Receptor: Crystal Structures of the GluR2 Ligand Binding Core Neali Armstrong and Eric Gouaux* mann, 1994; Nakanishi and Masu, 1994; Dingledine et al., Department of Biochemistry 1999). Receptors that are most sensitive to the synthetic and Molecular Biophysics agonist ␣-amino-3-hydroxy-5-methyl-4-isoxazole pro- Columbia University pionic acid (AMPA) are so-called AMPA receptors 650 West 168th Street (GluR1-4; Borges and Dingledine, 1998); receptors New York, New York 10032 activated by the naturally occurring neurotoxin and ago- nist kainate have been deemed kainate receptors (GluR5-7, KA1-2; Lerma et al., 1997; Chittajallu et al., 1999); and receptors that require both glycine and gluta- Summary mate for activation, but are also activated by synthetic N-methyl-D-aspartate, have been named NMDA recep- Crystal structures of the GluR2 ligand binding core tors (NMDAR1, NMDAR2a±d; Yamakura and Shimoji, (S1S2) have been determined in the apo state and in 1999). Although the ªorphanº ␦1 and ␦2 receptors (Lo- the presence of the antagonist DNQX, the partial agonist meli et al., 1993) neither bind glutamate nor form homo- kainate, and the full agonists AMPA and glutamate. meric channels, they are nevertheless implicated in mo- The domains of the S1S2 ligand binding core are ex- tor coordination (Kashiwabuchi et al., 1995), and panded in the apo state and contract upon ligand bind- mutations in these receptors can dramatically perturb ing with the extent of domain separation decreasing central nervous system function (Zuo et al., 1997).
    [Show full text]