DOCSLIB.ORG

Design, Synthesis and Anticancer Activity of New Polycyclic: Imidazole, Thiazine, Oxathiine, Pyrrolo-Quinoxaline and Thienotriazolopyrimidine Derivatives

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Design, Synthesis and Anticancer Activity of New Polycyclic: Imidazole, Thiazine, Oxathiine, Pyrrolo-Quinoxaline and Thienotriazolopyrimidine Derivatives molecules Article Design, Synthesis and Anticancer Activity of New Polycyclic: Imidazole, Thiazine, Oxathiine, Pyrrolo-Quinoxaline and Thienotriazolopyrimidine Derivatives Ameen Ali Abu-Hashem 1,2,* , Sami A. Al-Hussain 3 and Magdi E. A. Zaki 1,3 1 Heterocyclic Unit, National Research Centre, Photochemistry Department, Dokki, Giza 12622, Egypt; [email protected] or [email protected] 2 Chemistry Department, Faculty of Science, Jazan University, Jazan 45142, Saudi Arabia 3 Department of Chemistry, Faculty of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 13318, Saudi Arabia; [email protected] * Correspondence: [email protected] or [email protected]; Tel.: +20-012-2521-1700 or +966-591-363-915; Fax: +20-2-3337-0931 Abstract: In this article, we showed the synthesis of new polycyclic aromatic compounds, such as thienotriazolopyrimidinones, N-(thienotriazolopyrimidine) acetamide, 2-mercapto-thienotriazolo- pyrimidinones, 2-(((thieno-triazolopyrimidine) methyl) thio) thieno-triazolopyrimidines, thieno- pyrimidotriazolo-thiazines, pyrrolo-triazolo-thienopyrimidines, thienopyrimido-triazolopyrrolo- quinoxalines, thienopyrimido-triazolo-pyrrolo-oxathiino-quinoxalinones, 1,4-oxathiino-pyrrolo- tri- azolothienopyrimidinones, imidazopyrrolotriazolothienopyrimidines and 1,2,4-triazoloimidazo- pyrrolotriazolothienopyrimidindiones, based on the starting material 2,3-diamino-6-benzoyl-5- Citation: Abu-Hashem, A.A.; methylthieno[2,3-d]pyrimidin-4(3H)-one (3). The chemical structures were confirmed using many Al-Hussain, S.A.; Zaki, M.E.A. spectroscopic ways (IR, 1H, 13C, −NMR and MS) and elemental analyses. A series of thiazine, Design, Synthesis and Anticancer Activity of New Polycyclic: imidazole, pyrrole, thienotriazolopyrimidine derivatives were synthesized and evaluated for their Imidazole, Thiazine, Oxathiine, antiproliferative activity against four human cancer cell lines, i.e., CNE2 (nasopharyngeal), KB (oral), Pyrrolo-Quinoxaline and MCF-7 (breast) and MGC-803 (gastric) carcinoma cells. The compounds 20, 19, 17, 16 and 11 showed Thienotriazolopyrimidine significant cytotoxicity against types of human cancer cell lines. Derivatives. Molecules 2021, 26, 2031. https://doi.org/10.3390/ Keywords: thienopyrimidinone; thienotriazolopyrimidinone; 1,2,4-triazole; thiazine; pyrrole; molecules26072031 oxathiinoquinoxaline; imidazole; imidazopyrrolotriazole; anticancer activity Academic Editor: Brullo Chiara Received: 6 March 2021 1. Introduction Accepted: 23 March 2021 Published: 2 April 2021 Cancer is one of the most recent serious diseases that afflict humans and ultimately leads to their death. From here, researchers began to develop and discover much ef- Publisher’s Note: MDPI stays neutral fective anticancer therapeutics, such as treatment of cancer using chemotherapy [1] and with regard to jurisdictional claims in heterocyclic compounds, such as thienopyrimidine, triazolopyrimidine, quinoxaline and published maps and institutional affil- imidazole derivatives containing anticancer drugs [2], as follows: Azathioprine, Pimonida- iations. zole, Dacarbazine, Misonidazole, Fadrozole, Tipifarnib, Bendamustine, Indimitecan and Nilotinib. Therefore, the chemical studies of each of thiophene, pyrimidine, triazole, thiazine, pyrrole, quinoxaline and imidazole nucleus play a significant role in the syn- thesis of a diversity of fused heterocyclic compounds having a wide range of biologi- cal and pharmacological activities. Accordingly, previous scientific studies confirmed Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. that thienopyrimidine derivatives have various biological and pharmacological activi- This article is an open access article ties, such as antibiotics [3], antimicrobial [4,5], anticonvulsants [6], antiviral [7], antiox- distributed under the terms and idant and antitumor agents [8], anticancer [9] and mitotic arrest of breast cancer [10], conditions of the Creative Commons anti-inflammatory and analgesic activities [11,12], antiglaucoma agents [13], platelet ag- Attribution (CC BY) license (https:// gregation inhibitors [14], anti-hyperlipidemia [15], antidepressant, anti-inflammatory and creativecommons.org/licenses/by/ antimicrobial activities [16]. In addition, the thiazolopyrimidine, 1,2,4-triazolopy- rim- 4.0/). idine and thienotriazolopyrimidinone derivatives possess such biological activities as Molecules 2021, 26, 2031. https://doi.org/10.3390/molecules26072031 https://www.mdpi.com/journal/molecules Molecules 2021, 26, x FOR PEER REVIEW 2 of 21 Molecules 2021,[14],26, 2031 anti-hyperlipidemia [15], antidepressant, anti-inflammatory and antimicrobial activ- 2 of 20 ities [16]. In addition, the thiazolopyrimidine, 1, 2, 4-triazolopy- rimidine and thienotria- zolopyrimidinone derivatives possess such biological activities as anti-inflammatory and analgesic activityanti-inflammatory [17,18], antimicrobial and analgesic [19] an activityd anticancer [17,18 ],activity antimicrobial through [19 ]a andpotential anticancer of activity the enzyme (PARP-1)through inhibition a potential [20]. of the Lately, enzyme in connection (PARP-1) inhibition to continuing [20]. Lately, work in in connection the syn- to contin- thesis and biologicaluing workevaluation in the synthesis of new andpolycyclic biological fused evaluation thienopyrimidine, of new polycyclic purine fused and thienopyrim- 1,2,4-triazole systems,idine, purinepurine and derivatives 1,2,4-triazole are systems,of great purineimportance derivatives and wide are of applications great importance and in many biologicalwide activities, applications such in as many antitumor biological [21] activities, and the such potential as antitumor xanthine [21] oxidase and the potential (XO)-inhibitory activities,xanthine oxidase as well (XO)-inhibitoryas many biological activities, activities as well when as many fused biological with 1,2,4-tria- activities when fused with 1,2,4-triazole ring, shown in Figure1, as the following: 7 β-D-ribofuranosyl- zole ring, shown in Figure 1, as the following: 7β-D-ribofuranosyl-1,2,4-triazolopurines 1,2,4-triazolopurines (A) [22], 1,2,4-triazolopurines (B) [23], thienotriazolopyrimidinones (A) [22], 1,2,4-triazolopurines(C) and 2-sub-thienotriazolopyrimidinones (B) [23], thienotriazolopyrimidinones (D) as a new (C) class and of 2-sub-thieno- the XO inhibitors [24]. triazolopyrimidinonesAdditionally, (D) as Azathioprinea new class of (E) the is an XO anticancer inhibitors drug [24]. that Additionally, possesses considerable Azathio- potential, prine (E) is an anticancerbecause of drug its ability that possesses to interfere considerable with DNA prepared potential, and because then stop of growth its ability and division to interfere with cellsDNA and prepared it is used and for thethen treatment stop growth of metastatic and division malignant cells melanoma and it is andused cell for carcinoma the treatment of ofmetastatic the pancreas malignant [25]. melanoma and cell carcinoma of the pancreas [25]. Figure 1.FigureChemical 1. Chemical structures structures of formerly of synthesized formerly synthesize drugs: triazolopurinesd drugs: triazolopurines and thienotriazolo- and pyrimidinesthienotriazolo- analogues. pyrimidines analogues. The nitrogen atoms containing heterocycles, especially, display a different range of The nitrogenbiological atoms containing activities, due heterocycles to their similarities, especially, with numerous display synthetica different and range natural of molecules with recognized biological activities [26]. The benzimidazole and imidazole rings have biological activities, due to their similarities with numerous synthetic and natural mole- been generally used as the substantial basic structure for the development of therapeutic cules with recognizedmolecules biological of biological activities and pharmaceutical[26]. The benzimidazole activities. Anand example imidazole of five-memberedrings have been generallyheterocycles used as is the imidazole, substantial which basic is spread structure between for the the significant development biological of thera- building blocks. peutic moleculesThus, of biological many drugs and contain pharmaceutical imidazole, suchactivities. as the following:An example Sertaconazole of five-mem- is used as an bered heterocyclesantifungal is imidazole, agent [ 27which]. Omeprazole is spread is between antiulcer andthe controlssignificant the acidbiological secretion build- in the stomach ing blocks. Thus,and many it is drugs considered contain clinically imidazole, superior such to Has2-receptor the following: antagonists Sertaconazole [28,29]. Mizolastine is is used as an antifungalan antihistaminic agent [27]. andOmeprazole potent antagonist is antiulcer at H 1andreceptor controls sites the for theacid treatment secretion of allergic rhinoconjunctivitis and urticarial [30]. Candesartan is used as a receptor antagonist, because in the stomach and it is considered clinically superior to H2-receptor antagonists [28,29]. it contains a bulky lipophilic group, carboxylic acid, the biphenyl group that is more Mizolastine is an antihistaminic and potent antagonist at H1 receptor sites for the treat- efficient than the tetrazole analogue [31]. Azanidazole is an antiparasitic drug and used ment of allergic rhinoconjunctivitisas an antibacterial and and antiprotozoal urticarial [30]. drug Candesartan [32]. Maribavir is used is an as antiviral a receptor drug, which antagonist, becauseis used it contains in the treatment a bulky and lipop preventionhilic
Load more

Recommended publications
  • A Remarkable Case of Pterin Specific Oxidative Coupling: Unequivocal
    Tetrahedron Letters 57 (2016) 3277–3280 Contents lists available at ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet A remarkable case of pterin specific oxidative coupling: unequivocal synthesis of 6,7-alkoxypterins and 1,4-dioxanopterin with ceric ammonium nitrate ⇑ Manas Kumar Das a, Shyamaprosad Goswami a, , Ching Kheng Quah b, Hoong-Kun Fun b,c a Department of Chemistry, Indian Institute of Engineering and Science Technology, Shibpur, Howrah 711103, West Bengal, India b X-ray Crystallography Unit, School of Physics, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia c Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box. 2457, Riyadh 11451, Saudi Arabia article info abstract Article history: A facile and efficient synthesis of a series of methoxy and ethoxy substituted pterins (characterized by Received 3 May 2016 single crystal X-ray structures of 6,7-dimethoxy and diethoxy-pterins) along with 1,4-dioxanopterin is Revised 6 June 2016 reported along with a possible mechanism for their formation by treatment of pterins with ceric ammo- Accepted 8 June 2016 nium nitrate in methanol, ethanol, and ethylene glycol respectively. This unequivocal alkoxylation is Available online 16 June 2016 unique only with pterin (and 5-deaza-pterin) and is unsuccessful with quinoxaline. Ó 2016 Elsevier Ltd. All rights reserved. Keywords: Alkoxy pterin 1,4-Dioxano pterin Ceric ammonium nitrate Ethylene glycol Introduction O O (NH4)2Ce(NO3)6 N (4-5 equiv), ROH N OR O HN O HN Pterins are among the more important substructures in hetero- reflux, 2-3 h cycles, and their versatile properties make them more interesting N N N R=Me,Et N N N OR H H than other heterocycles such as quinoxalines, pyridines, pyrimidi- O nes etc.1 It is also known that the derivatives of pterin mainly (NH4)2Ce(NO3)6 N O (4-5 equiv), OH(CH2)2OH O HN include pterins and folates.
    [Show full text]
  • Investigating the Effect of the 2-Substituent
    molecules Communication Nucleophilic Substitution on 2-Monosubstituted Quinoxalines Giving 2,3-Disubstituted Quinoxalines: Investigating the Effect of the 2-Substituent Ndumiso Thamsanqa Ndlovu and Winston Nxumalo * Department of Chemistry, Faculty of Science and Agriculture, University of Limpopo, Private Bag X 1106, Sovenga 0727, South Africa; [email protected] * Correspondence: [email protected]; Tel.: +27-015-268-2331 Academic Editor: Philippe Belmont Received: 30 August 2016; Accepted: 23 September 2016; Published: 30 September 2016 Abstract: An investigation on the effect of substituent at the 2-position of mono-substituted quinoxalines in the synthesis of di-substituted quinoxaline derivatives via nucleophilic substitution reactions, is reported. Di-substituted quinoxalines bearing aryl-alky, aryl-aryl, aryl-heteroaryl, aryl-alkynyl, and amino-alkyl substituents were prepared in moderate to good yields. 2-Monosubstituted quinoxalines bearing a phenyl and butyl substituent reacted readily with alkyl-, aryl-, heteroaryl- and alkynyl- nucluephiles, giving di-substituted quinoxalines. 2-Monosubstituted quinoxalines bearing an amine and alkynyl substituent only reacted with alkyl nucleophiles. Oxidative rearomatization to give 2,3-disubstituted quinoxaline products occurred in atmospheric O2. Keywords: 2,3-disubsituted quinoxaline; nucleophilic substitution; oxidative rearomatization 1. Introduction Quinoxaline derivatives possess extensive applications in medicinal chemistry, due to their broad spectrum of biological activity [1,2]. A large number of synthetic quinoxalines have been reported to exhibit anti-tubercular [3], anti-viral [4,5], anti-microbial [6,7], and neuroprotective [8,9] activity. Quinoxaline derivatives have been reported to be prepared, but not limited, by intramolecular cyclisation of N-substituted aromatic ortho-diamines [10], ring transformation of benzofurazans [11], and condensation of benzofuran-1-oxide to form quinoxaline-N-oxides [12].
    [Show full text]
  • Electrooxidation Enables Highly Regioselective Dearomative Annulation of Indole and Benzofuran Derivatives
    ARTICLE https://doi.org/10.1038/s41467-019-13829-4 OPEN Electrooxidation enables highly regioselective dearomative annulation of indole and benzofuran derivatives Kun Liu1, Wenxu Song1, Yuqi Deng1, Huiyue Yang1, Chunlan Song1, Takfaoui Abdelilah1, Shengchun Wang 1, Hengjiang Cong 1, Shan Tang1 & Aiwen Lei1* 1234567890():,; The dearomatization of arenes represents a powerful synthetic methodology to provide three-dimensional chemicals of high added value. Here we report a general and practical protocol for regioselective dearomative annulation of indole and benzofuran derivatives in an electrochemical way. Under undivided electrolytic conditions, a series of highly functio- nalized five to eight-membered heterocycle-2,3-fused indolines and dihydrobenzofurans, which are typically unattainable under thermal conditions, can be successfully accessed in high yield with excellent regio- and stereo-selectivity. This transformation can also tolerate a wide range of functional groups and achieve good efficiency in large-scale synthesis under oxidant-free conditions. In addition, cyclic voltammetry, electron paramagnetic resonance (EPR) and kinetic studies indicate that the dehydrogenative dearomatization annulations arise from the anodic oxidation of indole into indole radical cation, and this process is the rate- determining step. 1 College of Chemistry and Molecular Sciences, Institute for Advanced Studies (IAS), Wuhan University, Wuhan 430072, P. R. China. *email: aiwenlei@whu. edu.cn NATURE COMMUNICATIONS | (2020) 11:3 | https://doi.org/10.1038/s41467-019-13829-4 | www.nature.com/naturecommunications 1 ARTICLE NATURE COMMUNICATIONS | https://doi.org/10.1038/s41467-019-13829-4 reaking the aromatic systems of electron-rich arenes or fused indolines (Fig. 1a)39–44. Therefore, it is highly appealing to heteroarenes provides three-dimensional chemicals of high develop efficient approaches to allow for their preparation.
    [Show full text]
  • )&F1y3x PHARMACEUTICAL APPENDIX to THE
    )&f1y3X PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE )&f1y3X PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 3 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. Product CAS No. Product CAS No. ABAMECTIN 65195-55-3 ACTODIGIN 36983-69-4 ABANOQUIL 90402-40-7 ADAFENOXATE 82168-26-1 ABCIXIMAB 143653-53-6 ADAMEXINE 54785-02-3 ABECARNIL 111841-85-1 ADAPALENE 106685-40-9 ABITESARTAN 137882-98-5 ADAPROLOL 101479-70-3 ABLUKAST 96566-25-5 ADATANSERIN 127266-56-2 ABUNIDAZOLE 91017-58-2 ADEFOVIR 106941-25-7 ACADESINE 2627-69-2 ADELMIDROL 1675-66-7 ACAMPROSATE 77337-76-9 ADEMETIONINE 17176-17-9 ACAPRAZINE 55485-20-6 ADENOSINE PHOSPHATE 61-19-8 ACARBOSE 56180-94-0 ADIBENDAN 100510-33-6 ACEBROCHOL 514-50-1 ADICILLIN 525-94-0 ACEBURIC ACID 26976-72-7 ADIMOLOL 78459-19-5 ACEBUTOLOL 37517-30-9 ADINAZOLAM 37115-32-5 ACECAINIDE 32795-44-1 ADIPHENINE 64-95-9 ACECARBROMAL 77-66-7 ADIPIODONE 606-17-7 ACECLIDINE 827-61-2 ADITEREN 56066-19-4 ACECLOFENAC 89796-99-6 ADITOPRIM 56066-63-8 ACEDAPSONE 77-46-3 ADOSOPINE 88124-26-9 ACEDIASULFONE SODIUM 127-60-6 ADOZELESIN 110314-48-2 ACEDOBEN 556-08-1 ADRAFINIL 63547-13-7 ACEFLURANOL 80595-73-9 ADRENALONE
    [Show full text]
  • Pharmaceutical Appendix to the Harmonized Tariff Schedule
    Harmonized Tariff Schedule of the United States (2019) Revision 13 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2019) Revision 13 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 Table 1. This table enumerates products described by International Non-proprietary Names INN which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service CAS registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known.
    [Show full text]
  • Vr Meds Ex01 3B 0825S Coding Manual Supplement Page 1
    vr_meds_ex01_3b_0825s Coding Manual Supplement MEDNAME OTHER_CODE ATC_CODE SYSTEM THER_GP PHRM_GP CHEM_GP SODIUM FLUORIDE A12CD01 A01AA01 A A01 A01A A01AA SODIUM MONOFLUOROPHOSPHATE A12CD02 A01AA02 A A01 A01A A01AA HYDROGEN PEROXIDE D08AX01 A01AB02 A A01 A01A A01AB HYDROGEN PEROXIDE S02AA06 A01AB02 A A01 A01A A01AB CHLORHEXIDINE B05CA02 A01AB03 A A01 A01A A01AB CHLORHEXIDINE D08AC02 A01AB03 A A01 A01A A01AB CHLORHEXIDINE D09AA12 A01AB03 A A01 A01A A01AB CHLORHEXIDINE R02AA05 A01AB03 A A01 A01A A01AB CHLORHEXIDINE S01AX09 A01AB03 A A01 A01A A01AB CHLORHEXIDINE S02AA09 A01AB03 A A01 A01A A01AB CHLORHEXIDINE S03AA04 A01AB03 A A01 A01A A01AB AMPHOTERICIN B A07AA07 A01AB04 A A01 A01A A01AB AMPHOTERICIN B G01AA03 A01AB04 A A01 A01A A01AB AMPHOTERICIN B J02AA01 A01AB04 A A01 A01A A01AB POLYNOXYLIN D01AE05 A01AB05 A A01 A01A A01AB OXYQUINOLINE D08AH03 A01AB07 A A01 A01A A01AB OXYQUINOLINE G01AC30 A01AB07 A A01 A01A A01AB OXYQUINOLINE R02AA14 A01AB07 A A01 A01A A01AB NEOMYCIN A07AA01 A01AB08 A A01 A01A A01AB NEOMYCIN B05CA09 A01AB08 A A01 A01A A01AB NEOMYCIN D06AX04 A01AB08 A A01 A01A A01AB NEOMYCIN J01GB05 A01AB08 A A01 A01A A01AB NEOMYCIN R02AB01 A01AB08 A A01 A01A A01AB NEOMYCIN S01AA03 A01AB08 A A01 A01A A01AB NEOMYCIN S02AA07 A01AB08 A A01 A01A A01AB NEOMYCIN S03AA01 A01AB08 A A01 A01A A01AB MICONAZOLE A07AC01 A01AB09 A A01 A01A A01AB MICONAZOLE D01AC02 A01AB09 A A01 A01A A01AB MICONAZOLE G01AF04 A01AB09 A A01 A01A A01AB MICONAZOLE J02AB01 A01AB09 A A01 A01A A01AB MICONAZOLE S02AA13 A01AB09 A A01 A01A A01AB NATAMYCIN A07AA03 A01AB10 A A01
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8,486,374 B2 Tamarkin Et Al
    USOO8486374B2 (12) United States Patent (10) Patent No.: US 8,486,374 B2 Tamarkin et al. (45) Date of Patent: Jul. 16, 2013 (54) HYDROPHILIC, NON-AQUEOUS (56) References Cited PHARMACEUTICAL CARRIERS AND COMPOSITIONS AND USES U.S. PATENT DOCUMENTS 1,159,250 A 11/1915 Moulton 1,666,684 A 4, 1928 Carstens (75) Inventors: Dov Tamarkin, Maccabim (IL); Meir 1924,972 A 8, 1933 Beckert Eini, Ness Ziona (IL); Doron Friedman, 2,085,733. A T. 1937 Bird Karmei Yosef (IL); Alex Besonov, 2,390,921 A 12, 1945 Clark Rehovot (IL); David Schuz. Moshav 2,524,590 A 10, 1950 Boe Gimzu (IL); Tal Berman, Rishon 2,586.287 A 2/1952 Apperson 2,617,754 A 1 1/1952 Neely LeZiyyon (IL); Jorge Danziger, Rishom 2,767,712 A 10, 1956 Waterman LeZion (IL); Rita Keynan, Rehovot (IL); 2.968,628 A 1/1961 Reed Ella Zlatkis, Rehovot (IL) 3,004,894 A 10/1961 Johnson et al. 3,062,715 A 11/1962 Reese et al. 3,067,784. A 12/1962 Gorman (73) Assignee: Foamix Ltd., Rehovot (IL) 3,092.255. A 6, 1963 Hohman 3,092,555 A 6, 1963 Horn 3,141,821 A 7, 1964 Compeau (*) Notice: Subject to any disclaimer, the term of this 3,142,420 A 7/1964 Gawthrop patent is extended or adjusted under 35 3,144,386 A 8/1964 Brightenback U.S.C. 154(b) by 1180 days. 3,149,543 A 9, 1964 Naab 3,154,075 A 10, 1964 Weckesser 3,178,352 A 4, 1965 Erickson (21) Appl.
    [Show full text]
  • European Surveillance of Healthcare-Associated Infections in Intensive Care Units
    TECHNICAL DOCUMENT European surveillance of healthcare-associated infections in intensive care units HAI-Net ICU protocol Protocol version 1.02 www.ecdc.europa.eu ECDC TECHNICAL DOCUMENT European surveillance of healthcare- associated infections in intensive care units HAI-Net ICU protocol, version 1.02 This technical document of the European Centre for Disease Prevention and Control (ECDC) was coordinated by Carl Suetens. In accordance with the Staff Regulations for Officials and Conditions of Employment of Other Servants of the European Union and the ECDC Independence Policy, ECDC staff members shall not, in the performance of their duties, deal with a matter in which, directly or indirectly, they have any personal interest such as to impair their independence. This is version 1.02 of the HAI-Net ICU protocol. Differences between versions 1.01 (December 2010) and 1.02 are purely editorial. Suggested citation: European Centre for Disease Prevention and Control. European surveillance of healthcare- associated infections in intensive care units – HAI-Net ICU protocol, version 1.02. Stockholm: ECDC; 2015. Stockholm, March 2015 ISBN 978-92-9193-627-4 doi 10.2900/371526 Catalogue number TQ-04-15-186-EN-N © European Centre for Disease Prevention and Control, 2015 Reproduction is authorised, provided the source is acknowledged. TECHNICAL DOCUMENT HAI-Net ICU protocol, version 1.02 Table of contents Abbreviations ...............................................................................................................................................
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2014/0271923 A1 Reid (43) Pub
    US 20140271923A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0271923 A1 Reid (43) Pub. Date: Sep. 18, 2014 (54) COMPOSITIONS & FORMULATIONS FOR (52) U.S. Cl. PREVENTING AND TREATING CHRONIC CPC ............. A6 IK3I/122 (2013.01); A61 K38/063 DISEASES THAT CLUSTER IN PATIENTS (2013.01); A61 K3I/496 (2013.01); A61 K SUCH AS CARDIOVASCULAR DISEASE, 45/06 (2013.01); A61 K31/4164 (2013.01); DLABETES, OBESITY, POLYCYSTIC OVARY A61K 31/12 (2013.01); A61 K3I/375 SYNDROME, HYPERLIPIDEMIA AND (2013.01); A61 K3I/355 (2013.01) HYPERTENSION, ASWELLAS FOR USPC ..... 424/651: 514/690: 514/21.9; 514/254.07; PREVENTING AND TREATING OTHER 514/383: 514/365: 514/256; 514/398: DISEASES AND CONDITIONS 514/236.2: 514/314: 514/154: 514/311; 514/31; 514/77; 514/39; 514/275; 514/253.08 (71) Applicant: Christopher Brian Reid, Los Angeles, CA (US) (57) ABSTRACT Patients inflicted with various clustering chronic diseases (72) Inventor: Christopher Brian Reid, Los Angeles, require treatment with multiple drugs having distinct mecha CA (US) nisms of action. Accordingly, patients with multiple condi tions suffer from cumulative side effects of multiple drugs as (21) Appl. No.: 13/815,664 well as drug-drug interactions. Embodiments, agents, com pounds or drugs of the present invention, such as sesquiter (22) Filed: Mar 14, 2013 penes, e.g., Zerumbone, replace an equal or larger number of approved drugs during patient treatment. Examples of disor Publication Classification ders prevented or ameliorated by administration of the for mulations of this invention include but are not limited to (51) Int.
    [Show full text]
  • Recent Trends in Synthesis of Quinoxaline and Its Derivatives *Dinesh Bharagava1 and Dr
    Dinesh Bharagava et al. / Journal of Pharmacy Research 2012,5(1),130-134 Review Article Available online through ISSN: 0974-6943 http://jprsolutions.info Recent trends in synthesis of quinoxaline and its derivatives *Dinesh Bharagava1 and Dr. Gopal Garg2 1Shekhawati College of Pharmacy, Dundlod, District-Jhunjhunu (Raj.) India 2VNS Institute of Pharmacy, Bhopal (M.P.) India Received on:20-09-2011; Revised on: 15-10-2011; Accepted on:10-12-2011 ABSTRACT Quinoxaline is nitrogen containing heterocyclic nucleus made up of benzene ring and pyrazine ring. It is a wonderful nucleus which gives almost all type of biological activity. So due to diversity in biological activity, it attracts the researchers to find out more its biological activity. But its traditional synthesis suffers from variety of disadvantage such as pollution, high cost, low yield, tedious work-up and long reaction time. Recently different methods have been developed for synthesis of quinoxaline derivatives by use of microwave and catalyst. In present study, we provide a concise review on history, chemistry, different methods of quinoxaline synthesis and its biological activity. Key words: Quinoxaline, o-Phenylenediamine, Diketones, Benzopyrazine, Quinoxalin-2-one INTRODUCTION 1 2. HISTORY 8 N N Quinoxaline is heterocyclic compound containing benzene ring and pyrazine 8 a 2 7 ring. Pyrazine is water soluble and stable colourless compound. In quinoxaline, benzene ring is fused with diazines compounds. The pyrazine ring system is present in the fungal metabolite aspergillic acid and also in luciferin. Methoxy 6 3 4 a pyrazine are essential component of aroma of many fruits and vegetables such N N 5 4 as capsicum and peas [32].
    [Show full text]
  • Recent Advances in the Synthesis of Benzimidazol (On) Es Via Rearrangements of Quinoxalin (On) Es
    RSC Advances View Article Online REVIEW View Journal | View Issue Recent advances in the synthesis of benzimidazol(on)es via rearrangements of Cite this: RSC Adv.,2016,6,42132 quinoxalin(on)es Vakhid A. Mamedov* This is the first review describing all the quinoxaline–benzimidazole rearrangements as a whole and the new quinoxalinone–benzimidazol(on)e rearrangements in particular when exposed to nucleophilic rearrangements for the synthesis of various biheterocyclic motifs. The scope of the rearrangements is Received 12th February 2016 illustrated by way of numerous examples of their application, and in doing so, the review contains over Accepted 2nd April 2016 131 references and covers all of the literature, from the first report of the rearrangement of 2,3- DOI: 10.1039/c6ra03907c diphenylquinoxaline by Ogg and Bergstrom in 1931 up to more recent examples in the past few years. www.rsc.org/advances The mechanisms for the selected transformations are also discussed. Creative Commons Attribution 3.0 Unported Licence. 1 Introduction its medicinal importance. The benzimidazole scaffold acts as an important class of heterocyclic compounds with a wide range of Benzimidazole, rstly described by Hobrecker in 1872,1 is an biological properties.6 Benzimidazole derivatives are structural important privileged heterocyclic motif2–5 and one of the most isosteres of naturally occurring nucleotides, which allow them widely investigated scaffolds by synthetic chemists because of to easily interact with the biopolymers of the living systems and different kinds of biological activity have been obtained. 2- Aminobenzimidazoles proved useful for acid/base catalysis and A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientic Center of can substitute guanidinium groups in receptor molecules the Russian Academy of Sciences, Arbuzov str.
    [Show full text]
  • Essentials of Heterocyclic Chemistry-I Heterocyclic Chemistry
    Baran, Richter Essentials of Heterocyclic Chemistry-I Heterocyclic Chemistry 5 4 Deprotonation of N–H, Deprotonation of C–H, Deprotonation of Conjugate Acid 3 4 3 4 5 4 3 5 6 6 3 3 4 6 2 2 N 4 4 3 4 3 4 3 3 5 5 2 3 5 4 N HN 5 2 N N 7 2 7 N N 5 2 5 2 7 2 2 1 1 N NH H H 8 1 8 N 6 4 N 5 1 2 6 3 4 N 1 6 3 1 8 N 2-Pyrazoline Pyrazolidine H N 9 1 1 5 N 1 Quinazoline N 7 7 H Cinnoline 1 Pyrrolidine H 2 5 2 5 4 5 4 4 Isoindole 3H-Indole 6 Pyrazole N 3 4 Pyrimidine N pK : 11.3,44 Carbazole N 1 6 6 3 N 3 5 1 a N N 3 5 H 4 7 H pKa: 19.8, 35.9 N N pKa: 1.3 pKa: 19.9 8 3 Pyrrole 1 5 7 2 7 N 2 3 4 3 4 3 4 7 Indole 2 N 6 2 6 2 N N pK : 23.0, 39.5 2 8 1 8 1 N N a 6 pKa: 21.0, 38.1 1 1 2 5 2 5 2 5 6 N N 1 4 Pteridine 4 4 7 Phthalazine 1,2,4-Triazine 1,3,5-Triazine N 1 N 1 N 1 5 3 H N H H 3 5 pK : <0 pK : <0 3 5 Indoline H a a 3-Pyrroline 2H-Pyrrole 2-Pyrroline Indolizine 4 5 4 4 pKa: 4.9 2 6 N N 4 5 6 3 N 6 N 3 5 6 3 N 5 2 N 1 3 7 2 1 4 4 3 4 3 4 3 4 3 3 N 4 4 2 6 5 5 5 Pyrazine 7 2 6 Pyridazine 2 3 5 3 5 N 2 8 N 1 2 2 1 8 N 2 5 O 2 5 pKa: 0.6 H 1 1 N10 9 7 H pKa: 2.3 O 6 6 2 6 2 6 6 S Piperazine 1 O 1 O S 1 1 Quinoxaline 1H-Indazole 7 7 1 1 O1 7 Phenazine Furan Thiophene Benzofuran Isobenzofuran 2H-Pyran 4H-Pyran Benzo[b]thiophene Effects of Substitution on Pyridine Basicity: pKa: 35.6 pKa: 33.0 pKa: 33.2 pKa: 32.4 t 4 Me Bu NH2 NHAc OMe SMe Cl Ph vinyl CN NO2 CH(OH)2 4 8 5 4 9 1 3 2-position 6.0 5.8 6.9 4.1 3.3 3.6 0.7 4.5 4.8 –0.3 –2.6 3.8 6 3 3 5 7 4 8 2 3 5 2 3-position 5.7 5.9 6.1 4.5 4.9 4.4 2.8 4.8 4.8 1.4 0.6 3.8 4 2 6 7 7 3 N2 N 1 4-position
    [Show full text]