Drug Discovery and Development
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Supplementary Information
Supplementary Information Network-based Drug Repurposing for Novel Coronavirus 2019-nCoV Yadi Zhou1,#, Yuan Hou1,#, Jiayu Shen1, Yin Huang1, William Martin1, Feixiong Cheng1-3,* 1Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA 2Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44195, USA 3Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA #Equal contribution *Correspondence to: Feixiong Cheng, PhD Lerner Research Institute Cleveland Clinic Tel: +1-216-444-7654; Fax: +1-216-636-0009 Email: [email protected] Supplementary Table S1. Genome information of 15 coronaviruses used for phylogenetic analyses. Supplementary Table S2. Protein sequence identities across 5 protein regions in 15 coronaviruses. Supplementary Table S3. HCoV-associated host proteins with references. Supplementary Table S4. Repurposable drugs predicted by network-based approaches. Supplementary Table S5. Network proximity results for 2,938 drugs against pan-human coronavirus (CoV) and individual CoVs. Supplementary Table S6. Network-predicted drug combinations for all the drug pairs from the top 16 high-confidence repurposable drugs. 1 Supplementary Table S1. Genome information of 15 coronaviruses used for phylogenetic analyses. GenBank ID Coronavirus Identity % Host Location discovered MN908947 2019-nCoV[Wuhan-Hu-1] 100 Human China MN938384 2019-nCoV[HKU-SZ-002a] 99.99 Human China MN975262 -
Targeting Multidrug Resistance Proteins and C-Type Natriuretic Peptide to Optimise Cyclic GMP Signalling in Cardiovascular Disease
Targeting multidrug resistance proteins and C-type natriuretic peptide to optimise cyclic GMP signalling in cardiovascular disease Robert Matthew Henry Grange Submitted in partial fulfilment of the requirements of the Degree of Doctor of Philosophy Heart Centre William Harvey Research Institute Barts & The London School of Medicine & Dentistry Queen Mary University of London Charterhouse Square London EC1M 6BQ United Kingdom STATEMENT OF ORIGINALITY I, Robert Matthew Henry Grange, confirm that the research included within this thesis is my own work or that where it has been carried out in collaboration with, or supported by others, that this is duly acknowledged below and my contribution indicated. Previously published material is also acknowledged below. I attest that I have exercised reasonable care to ensure that the work is original, and does not to the best of my knowledge break any UK law, infringe any third party’s copyright or other Intellectual Property Right, or contain any confidential material. I accept that the College has the right to use plagiarism detection software to check the electronic version of the thesis. I confirm that this thesis has not been previously submitted for the award of a degree by this or any other university. The copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the author. Signature: Date: 05/05/2016 I PUBLISHED ABSTRACTS Allen RMH, Renukanthan A, Bubb KJ, Villar IC, Moyes AJ, Baliga RS, Hobbs AJ. Investigation of the role of multidrug resistance proteins (MRPs) in vascular homeostasis. -
Evaluation of the Allometric Exponents in Prediction of Human Drug Clearance
Virginia Commonwealth University VCU Scholars Compass Theses and Dissertations Graduate School 2014 Evaluation of the Allometric Exponents in Prediction of Human Drug Clearance Da Zhang Virginia Commonwealth University Follow this and additional works at: https://scholarscompass.vcu.edu/etd Part of the Other Pharmacy and Pharmaceutical Sciences Commons © The Author Downloaded from https://scholarscompass.vcu.edu/etd/3533 This Dissertation is brought to you for free and open access by the Graduate School at VCU Scholars Compass. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of VCU Scholars Compass. For more information, please contact [email protected]. ©Da Zhang, 2014 All Rights Reserve EVALUATION OF THE ALLOMETRIC EXPONENTS IN PREDICTION OF HUMAN DRUG CLEARANCE A Dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University By Da Zhang Master of Science, University of Arizona, 2004 Director: F. Douglas Boudinot, Ph.D. Professor, School of Pharmacy, VCU Virginia Commonwealth University Richmond, Virginia August, 2014 ACKNOWLEDGEMENTS First and foremost, I would like to sincerely thank my advisor, Dr. F. Douglas Boudinot, for giving me the opportunity to pursue graduate studies under his guidance and for his continuous professional support, guidance, encouragement and patience throughout my graduate program. He was always delighted in sharing his vast knowledge and kind warmth. I would also like to thank Dr. Ahmad for his scientific advice and support through the complet ion of my degree. He has been a kind and helpful mentor for me. I would like to acknowledge my graduate committee members, Drs. -
Pharmaceuticals As Environmental Contaminants
PharmaceuticalsPharmaceuticals asas EnvironmentalEnvironmental Contaminants:Contaminants: anan OverviewOverview ofof thethe ScienceScience Christian G. Daughton, Ph.D. Chief, Environmental Chemistry Branch Environmental Sciences Division National Exposure Research Laboratory Office of Research and Development Environmental Protection Agency Las Vegas, Nevada 89119 [email protected] Office of Research and Development National Exposure Research Laboratory, Environmental Sciences Division, Las Vegas, Nevada Why and how do drugs contaminate the environment? What might it all mean? How do we prevent it? Office of Research and Development National Exposure Research Laboratory, Environmental Sciences Division, Las Vegas, Nevada This talk presents only a cursory overview of some of the many science issues surrounding the topic of pharmaceuticals as environmental contaminants Office of Research and Development National Exposure Research Laboratory, Environmental Sciences Division, Las Vegas, Nevada A Clarification We sometimes loosely (but incorrectly) refer to drugs, medicines, medications, or pharmaceuticals as being the substances that contaminant the environment. The actual environmental contaminants, however, are the active pharmaceutical ingredients – APIs. These terms are all often used interchangeably Office of Research and Development National Exposure Research Laboratory, Environmental Sciences Division, Las Vegas, Nevada Office of Research and Development Available: http://www.epa.gov/nerlesd1/chemistry/pharma/image/drawing.pdfNational -
Compositions Comprising Nebivolol
(19) TZZ ZZ__T (11) EP 2 808 015 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 03.12.2014 Bulletin 2014/49 A61K 31/34 (2006.01) A61K 31/502 (2006.01) A61K 31/353 (2006.01) A61P 9/00 (2006.01) (21) Application number: 14002458.9 (22) Date of filing: 16.11.2005 (84) Designated Contracting States: • O’Donnell, John AT BE BG CH CY CZ DE DK EE ES FI FR GB GR Morgantown, WV 26505 (US) HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI • Bottini, Peter Bruce SK TR Morgantown, WV 26505 (US) • Mason, Preston (30) Priority: 31.05.2005 US 141235 Morgantown, WV 26504 (US) 10.11.2005 US 272562 • Shaw, Andrew Preston 15.11.2005 US 273992 Morgantown, WV 26504 (US) (62) Document number(s) of the earlier application(s) in (74) Representative: Samson & Partner accordance with Art. 76 EPC: Widenmayerstraße 5 09015249.7 / 2 174 658 80538 München (DE) 05848185.4 / 1 890 691 Remarks: (71) Applicant: MYLAN LABORATORIES, INC This application was filed on 16-07-2014 as a Morgantown, NV 26504 (US) divisional application to the application mentioned under INID code 62. (72) Inventors: • Davis, Eric Morgantown, WV 26508 (US) (54) Compositions comprising nebivolol (57) The active ingredients of the pharmaceutical composition described consist of nebivolol, one or more ACE inhibitors and one or more ARB. EP 2 808 015 A1 Printed by Jouve, 75001 PARIS (FR) EP 2 808 015 A1 Description [0001] This application is a continuation-in-part of application Ser. -
United States Patent (19) 11 Patent Number: 4,822,930 Liu 45 Date of Patent: Apr
United States Patent (19) 11 Patent Number: 4,822,930 Liu 45 Date of Patent: Apr. 18, 1989 (54) PROCESS FOR PREPARING 3,890,326 6/1975 Tobin .................................. 570/206 MONOBROMINATED CYCLOBUTARENES 4,540,763 9/1985 Kirchhoff............................ 526/281 (75) Inventor: Ming-Biann Liu, Midland, Mich. OTHER PUBLICATIONS (73) Assignee: The Dow Chemical Company, Lloyd et al., "The Electrophilic Substitution of Ben Midland, Mich. zocyclobutene-II', Tetrahedron, 1965, vol. 21, pp. 245 (21) Appl. No.: 64,714 to 254. Lloyd et al., "Tetrahedron', vol. 20, pp. 2184-2194 22) Filed: Jun. 22, 1987 (1964). (51) Int. Cl'....................... C07C21/24: CO7C 17/00 52 U.S. C. .................................... 570/206; 570/207; Primary Examiner-Werren B. Lone 570/208; 570/209; 570/211 57 ABSTRACT 58) Field of Search ............... 570/206, 207,208, 209, Monobrominated cyclobutarenes are prepared by bro 570/210 minating a cyclobutarene in the presence of an organic (56) References Cited complexing agent, an acid scavenger, or water. Faster U.S. PATENT DOCUMENTS reaction rates highly selective to monobrominated cy clobutarenes are obtained without conventional heavy 3,420,035 2/1969 Bremmer ............................. 570/206 metal or halogen catalysts. 3,607,883 9/1971 Schneider ........ ... 570/206 3,755,444 8/1973 Schneider et al. .................. 570/206 3,763,248 10/1973 Mitchell .............................. 570/206 32 Claims, No Drawings 4,822,930 1. 2 high performance monomeric and polymeric composi PROCESS FOR PREPARNG tions for the electronics industry. MONOBROMINATED CYCLOBUTARENES DETALED DESCRIPTION OF THE BACKGROUND OF THE INVENTION 5 INVENTION This invention relates to a process for preparing bro As the term is used herein, "cyclobutarene' refers to minated organic compounds. -
(12) United States Patent (10) Patent No.: US 7.414,133 B2 Stössel Et Al
USOO7414133B2 (12) United States Patent (10) Patent No.: US 7.414,133 B2 Stössel et al. (45) Date of Patent: Aug. 19, 2008 (54) PALLADIUMAND PLATINUM COMPLEXES (58) Field of Classification Search ..................... 546/2: 549/3, 206; 313/504; 257/40: 528/423; (75) Inventors: Philipp Stössel, Frankfurt (DE); Ingrid 526/265 Bach, Bad Soden (DE); Hubert See application file for complete search history. Spreitzer, Viernheim (DE) (56) References Cited (73) Assignee: Merck Patent GmbH U.S. PATENT DOCUMENTS 4,539,507 A 9/1985 VanSlyke et al. (*) Notice: Subject to any disclaimer, the term of this 5,151,629 A 9/1992 VanSlyke patent is extended or adjusted under 35 5,621,131 A 4/1997 Kreuder et al. U.S.C. 154(b) by 637 days. 5,679,760 A 10, 1997 Mullen et al. 5,763,636 A 6/1998 Kreuder et al. (21) Appl. No.: 10/534,173 6,653,438 B1 1 1/2003 Spreitzer et al. 2004/O1384.55 A1 7/2004 Stossel et al. (22) PCT Filed: Nov. 4, 2003 FOREIGN PATENT DOCUMENTS EP O 707 O2O 4f1996 (86). PCT No.: PCT/EPO3/12279 EP O 842 208 5, 1998 EP O 894 107 2, 1999 S371 (c)(1), EP 1 O28 136 8, 2000 (2), (4) Date: May 6, 2005 EP 1 191 613 3, 2002 EP 1238981 9, 2002 WO WO-92, 18552 10, 1992 (87) PCT Pub. No.: WO2004/041835 WO WO-O2, 15645 2, 2000 WO WO-OO.22026 4/2000 PCT Pub. Date: May 21, 2004 WO WO-O2/O68435 9, 2002 (65) Prior Publication Data Primary Examiner P. -
Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DIX to the HTSUS—Continued
20558 Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DEPARMENT OF THE TREASURY Services, U.S. Customs Service, 1301 TABLE 1.ÐPHARMACEUTICAL APPEN- Constitution Avenue NW, Washington, DIX TO THE HTSUSÐContinued Customs Service D.C. 20229 at (202) 927±1060. CAS No. Pharmaceutical [T.D. 95±33] Dated: April 14, 1995. 52±78±8 ..................... NORETHANDROLONE. A. W. Tennant, 52±86±8 ..................... HALOPERIDOL. Pharmaceutical Tables 1 and 3 of the Director, Office of Laboratories and Scientific 52±88±0 ..................... ATROPINE METHONITRATE. HTSUS 52±90±4 ..................... CYSTEINE. Services. 53±03±2 ..................... PREDNISONE. 53±06±5 ..................... CORTISONE. AGENCY: Customs Service, Department TABLE 1.ÐPHARMACEUTICAL 53±10±1 ..................... HYDROXYDIONE SODIUM SUCCI- of the Treasury. NATE. APPENDIX TO THE HTSUS 53±16±7 ..................... ESTRONE. ACTION: Listing of the products found in 53±18±9 ..................... BIETASERPINE. Table 1 and Table 3 of the CAS No. Pharmaceutical 53±19±0 ..................... MITOTANE. 53±31±6 ..................... MEDIBAZINE. Pharmaceutical Appendix to the N/A ............................. ACTAGARDIN. 53±33±8 ..................... PARAMETHASONE. Harmonized Tariff Schedule of the N/A ............................. ARDACIN. 53±34±9 ..................... FLUPREDNISOLONE. N/A ............................. BICIROMAB. 53±39±4 ..................... OXANDROLONE. United States of America in Chemical N/A ............................. CELUCLORAL. 53±43±0 -
X-Ray Fluorescence Analysis Method Röntgenfluoreszenz-Analyseverfahren Procédé D’Analyse Par Rayons X Fluorescents
(19) & (11) EP 2 084 519 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: G01N 23/223 (2006.01) G01T 1/36 (2006.01) 01.08.2012 Bulletin 2012/31 C12Q 1/00 (2006.01) (21) Application number: 07874491.9 (86) International application number: PCT/US2007/021888 (22) Date of filing: 10.10.2007 (87) International publication number: WO 2008/127291 (23.10.2008 Gazette 2008/43) (54) X-RAY FLUORESCENCE ANALYSIS METHOD RÖNTGENFLUORESZENZ-ANALYSEVERFAHREN PROCÉDÉ D’ANALYSE PAR RAYONS X FLUORESCENTS (84) Designated Contracting States: • BURRELL, Anthony, K. AT BE BG CH CY CZ DE DK EE ES FI FR GB GR Los Alamos, NM 87544 (US) HU IE IS IT LI LT LU LV MC MT NL PL PT RO SE SI SK TR (74) Representative: Albrecht, Thomas Kraus & Weisert (30) Priority: 10.10.2006 US 850594 P Patent- und Rechtsanwälte Thomas-Wimmer-Ring 15 (43) Date of publication of application: 80539 München (DE) 05.08.2009 Bulletin 2009/32 (56) References cited: (60) Divisional application: JP-A- 2001 289 802 US-A1- 2003 027 129 12164870.3 US-A1- 2003 027 129 US-A1- 2004 004 183 US-A1- 2004 017 884 US-A1- 2004 017 884 (73) Proprietors: US-A1- 2004 093 526 US-A1- 2004 235 059 • Los Alamos National Security, LLC US-A1- 2004 235 059 US-A1- 2005 011 818 Los Alamos, NM 87545 (US) US-A1- 2005 011 818 US-B1- 6 329 209 • Caldera Pharmaceuticals, INC. US-B2- 6 719 147 Los Alamos, NM 87544 (US) • GOLDIN E M ET AL: "Quantitation of antibody (72) Inventors: binding to cell surface antigens by X-ray • BIRNBAUM, Eva, R. -
PERKIN a Concise Synthesis of Carpanone Using Solid-Supported Reagents and Scavengers
PERKIN A concise synthesis of carpanone using solid-supported reagents and scavengers Ian R. Baxendale, Ai-Lan Lee and Steven V. Ley* Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UK CB2 1EW. E-mail: [email protected]; Fax: ϩ44 (0) 1223 336442; 1 Tel: ϩ44 (0) 1223 336398 Received (in Cambridge, UK) 5th April 2002, Accepted 26th June 2002 First published as an Advance Article on the web 18th July 2002 Polymer-supported reagents have been applied to the synthesis of the natural product carpanone resulting in a clean and efficient synthesis without the requirement for conventional purification techniques. A new polymer-supported transition metal isomerisation catalyst is also reported. Introduction Table 1 Claisen rearrangement of substrate 4 The utilisation of solid-supported reagents in chemical Microwave at 220 ЊC Conversion (%) synthesis has been shown to markedly improve productivity in many critical aspects of the generation of new chemical entities 3 × 15 min 97 and complex target molecules. The potential to configure the 30 min continuous 78 reactions in both a serial and convergent fashion offers many 45 min continuous 86 ϩ ϩ ϩ ϩ ϩ ϩ ϩ distinct advantages compared to solid-phase synthesis. In 2 2 2 1 1 15 15 15 min 85 addition the simple removal of spent reagents through filtration enables reactions to be driven to completion through the addition of excess reagents and for lower yielding reactions to be cleaned-up using scavenger resins. We have previously reported on the use of these concepts in the sequential multi-step synthesis of various natural products using solid-supported reagents and scavengers to effect all the individual steps.1 As a consequence, no chromatographic purification procedures were necessary and all stages proceeded with simple and rapid optimisation. -
(12) United States Patent (10) Patent No.: US 6,388,135 B1 L0chtman Et Al
USOO6388135B1 (12) United States Patent (10) Patent No.: US 6,388,135 B1 L0chtman et al. (45) Date of Patent: May 14, 2002 (54) PREPARATION OF 4-BROMOANILINE WO WO 98/31681 7/1998 DERVATIVES WO WO 99/58509 11/1999 (75) Inventors: Rene Lochtman, Mannheim; Michael OTHER PUBLICATIONS Keil, Freinsheim; Joachim Gebhardt, Wachenheim; Michael Rack, Miller et al. “Methoden Der Organischen Chemie' Band Heidelberg; Wolfgang von Deyn, V/4 (1960) pp. 240–242 & 274-249. Neustadt, all of (DE) (73) Assignee: BASF Aktiengesellschaft, Primary Examiner Samuel Barts Ludwigshafen (DE) (74) Attorney, Agent, or Firm-Keil & Weinkauf (*) Notice: Subject to any disclaimer, the term of this (57) ABSTRACT patent is extended or adjusted under 35 U.S.C. 154(b) by 0 days. A process for preparing 4-bromoaniline derivatives of the formula I (21) Appl. No.: 09/894,006 (22) Filed: Jun. 29, 2001 Related U.S. Application Data Br R2 (60) Provisional application No. 60/219,410, filed on Jul. 20, 2000. (30) Foreign Application Priority Data Jun. 30, 2000 (DE) ......................................... 10O3O 975 where: (51) Int. Cl." .............................................. C07C 209/00 (52) U.S. Cl. ....................... 564/412; 548/240; 548/247; R" is C1-Co-alkyl, C-C-haloalkyl, C1-Co-alkoxy, 558/418 C-C-haloalkoxy, C-C-cycloalkyl, halogen (58) Field of Search .......................... 564/412; 548/240, R is C-C-alkyl, C-C-alkoxy, Ca-Cs-cycloalkyl, 548/247; 558/418 C-C-alkenyl, cyano or a heterocyclic radical is described. (56) References Cited FOREIGN PATENT DOCUMENTS CA 22783.31 7/1998 30 Claims, No Drawings US 6,388,135 B1 1 2 PREPARATION OF 4-BROMOANILINE which comprises reacting a compound of the formula II DERVATIVES II R1 The present application claims priority of prior provi sional application Serial No. -
A Study of the Formation of Carbenes by Elimination of Α-Bromosilanes and Application Toward the Synthesis of Transition Metal Complexed Quinone Methide Analogs
University of Arkansas, Fayetteville ScholarWorks@UARK Theses and Dissertations 8-2012 Part I - A Study of the Formation of Carbenes by Elimination of α-Bromosilanes and Application toward the Synthesis of Transition Metal Complexed Quinone Methide Analogs. Part II - Development of Novel 7-Membered Ring Carbene Ligands for Palladium Catalyzed Cross Coupling Reactions. Christian Michael Loeschel University of Arkansas, Fayetteville Follow this and additional works at: http://scholarworks.uark.edu/etd Part of the Biochemistry Commons, Inorganic Chemistry Commons, and the Organic Chemistry Commons Recommended Citation Loeschel, Christian Michael, "Part I - A Study of the Formation of Carbenes by Elimination of α-Bromosilanes and Application toward the Synthesis of Transition Metal Complexed Quinone Methide Analogs. Part II - Development of Novel 7-Membered Ring Carbene Ligands for Palladium Catalyzed Cross Coupling Reactions." (2012). Theses and Dissertations. 437. http://scholarworks.uark.edu/etd/437 This Dissertation is brought to you for free and open access by ScholarWorks@UARK. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of ScholarWorks@UARK. For more information, please contact [email protected], [email protected]. PART I - A STUDY OF THE FORMATION OF CARBENES BY ELIMINATION OF α- BROMOSILANES AND APPLICATION TOWARD THE SYNTHESIS OF TRANSITION METAL COMPLEXED QUINONE METHIDE ANALOGS PART II - DEVELOPMENT OF NOVEL 7-MEMBERED RING CARBENE LIGANDS FOR PALLADIUM CATALYZED CROSS COUPLING REACTIONS