DOCSLIB.ORG

US 2012/0277430 A1 TANGUCH Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
US 2012/0277430 A1 TANGUCH Et Al US 20120277430A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2012/0277430 A1 TANGUCH et al. (43) Pub. Date: Nov. 1, 2012 (54) PYRIDAZINONE COMPOUNDS (52) U.S. Cl. ........................................................ 544/238 (57) ABSTRACT (76) Inventors: Takahiko TANGUCHI, Cambridge (GB); Jun Kunitomo, The present invention provides a compound which has the Kanagawa (JP) effect of PDE inhibition, and which is useful as a medicament for preventing or treating schizophrenia or so on. A com pound of formula (I), wherein R1 represents a substituent; (21) Appl. No.: 13/543,296 R2 represents a hydrogen atom, or a Substituent; R3 repre sents a hydrogenatom, or a substituent; Ring. A represents an (22) Filed: Jul. 6, 2012 aromatic ring which can be substituted, and Ring Brepresents a 5-membered heteroaromatic ring which can be substituted, Related U.S. Application Data or a salt thereof. (62) Division of application No. 13/148,172, filed on Oct. 20, 2011, filed as application No. PCT/US2010/ (Io) 000307 on Feb. 4, 2010. (60) Provisional application No. 61/202,207, filed on Feb. 5, 2009, provisional application No. 61/213,927, filed on Jul 30, 2009. Publication Classification (51) Int. Cl. CO7D 403/14 (2006.01) Patent Application Publication Nov. 1, 2012 Sheet 1 of 3 US 2012/0277430 A1 2.50 2.00 1.50 1.OO . 0.50 O.OO ... Vehicle 3 10 30 Compound A (mg/kg, i.p.) Fig. 1A 0.25 0.20 - 0. 15 ------------ 0. 10 0.05 - 0.00 - --- vehicle 3 Compound A Fig. 1B "control OCompound A: 3 Z Compound A: 10 8 Compound A: 30 a Compound A:100 (in g/kg, ip.) -30t O 0 min O to 90 m in Fig. 2A Patent Application Publication Nov. 1, 2012 Sheet 2 of 3 US 2012/0277430 A1 control Compound A: 3 2) Compound A: 10 Compound A: 30 (in g/kg, ip) -30 to Omin O to 90 min Fig. 2B i * O O O 1 3 10 30 RS O.3 Compound A (mg/kg, i.p.) MK-801 (0.3 mg/kg, s.c.) - Fig. 3 Patent Application Publication Nov. 1, 2012 Sheet 3 of 3 US 2012/0277430 A1 3000 2500 2000 squnooA??a?oe 1500 1000 -60 to 0 min O to 90 min Fig. 4 US 2012/0277430 A1 Nov. 1, 2012 PYRIDAZINONE COMPOUNDS medications, D or D/5-HT, antagonists, mainly derives from their activation of the indirect pathway in the striatum. TECHNICAL FIELD As PDE10A inhibitors are able to activate this pathway, this Suggests that PDE10A inhibitors are promising as antipsy 0001. The present invention relates to pyridazinone com chotic drugs. The excessive D receptor antagonism in the pounds. brain by Dantagonists causes problems of extrapyramidal side effects and hyperprolactinaemia. However the expres sion of PDE10A is limited to these striatal pathways in the BACKGROUND OF THE INVENTION brain, thus side effects by PDE10A inhibitors were expected to be weaker compared with current Dantagonists. Regard 0002 Phosphodiesterases (PDEs) are a superfamily of ing hyperprolactinaemia, PDE10A inhibitors would produce enzymes encoded by 21 genes and Subdivided into 11 distinct no prolactin elevation due to lack of D receptor antagonism families according to structural and functional properties. in the pituitary. Moreover, the presence of PDE10A in a direct These enzymes metabolically inactivate the ubiquitous intra pathway makes it likely that PDE10A inhibition will have cellular second messengers, cyclic adenosine monophos some advantage over current Dantagonists; the direct path phate (cAMP) and cyclic guanosine monophosphate way is thought to promote desired action, and activation of (cGMP): PDEs selectively catalyze the hydrolysis of the this pathway by PDE10A inhibitors may counteract extrapy 3'-ester bond, forming the inactive 5'-monophosphate. On the ramidal symptoms induced by excessive D receptor antago basis of substrate specificity, the PDE families can be further nism. In addition, activation of this pathway could facilitate striatal-thalamic outflow, promoting the execution of proce classified into three groups: i) the cAMP-PDEs (PDE4, dural Strategies. Furthermore, enhancement of second mes PDE7, PDE8), ii) the coMP-PDEs (PDE5, PDE6 and PDE9), senger levels without blockade of dopamine and/or other and iii) the dual-substrate PDEs (PDE1, PDE2, PDE3, neurotransmitter receptors may also provide therapeutic PDE10 and PDE11). advantages with fewer adverse side-effects compared with 0003. The cAMP and coMP are involved in the regulation current antipsychotics (e.g., hyperprolactinaemia and weight of virtually every physiological process Such as pro-inflam gain). This unique distribution and function in the brain indi matory mediator production and action, ion channel function, cates that PDE10A represents an important new target for the muscle relaxation, learning and memory formation, differen treatment of neurological and psychiatric disorders, in par tiation, apoptosis, lipogenesis, glycogenolysis and gluconeo ticular psychotic disorders like Schizophrenia. genesis. Especially, in neurons, these second messengers 0005. As a phosphodiesterase (PDE)10 inhibitor, a com have important role in the regulation of synaptic transmission pound represented by the formula: as well as in neuronal differentiation and survival (Nat. Rev. Drug Discov. 2006, vol. 5: 660-670). Regulation of these processes by cAMP and ccjMP are accompanied by activa tion of protein kinase A(PKA) and protein kinase G (PKG), which in turn phosphorylate a variety of substrates, including transcription factors, ion channels and receptors that regulate a variety of physiological processes. Intracellular cAMP and cGMP concentrations seem to be temporally, spatially, and functionally compartmentalized by regulation of adenyl and guanyl cyclases in response to extracellular signaling and their degradation by PDEs (Circ. Res. 2007, vol. 100(7): 0006 wherein Z is 950-966). PDEs provide the only means of degrading the cyclic nucleotides cAMP and ccjMP in cells, thus PDEs play an essential role in cyclic nucleotide signaling. Thereby, i PDEs could be promising targets for various therapeutic 21 drugs. Y N X 0004 Phosphodiesterase 10A (PDE10A) was discovered y 1 n n Nx N X in 1999 by three independent groups (Proc. Natl. Acad. Sci. USA 1999, vol.96: 8991-8996, J. Biol. Chem. 1999, vol. 274: Y Y 18438-18445, Gene 1999, vol. 234: 109-117). Expression N4N4 studies have shown that PDE10A has the most restricted 0007) was disclosed in WO2006/072828 Pamphlet. distribution within the all known PDE families; the PDE10A 0008 Further, as aphosphodiesterase (PDE)10 inhibitor, a mRNA is highly expressed only in brain and testes (Eur. J. compound represented by the general formula Biochem. 1999, vol. 266: 1118-1127, J. Biol. Chem. 1999, (I) vol. 274: 18438-18445). In the brain, mRNA and protein of PDE10A are highly enriched in medium spiny neurons (MSNs) of the striatum (Eur. J. Biochem. 1999, vol. 266: 1118-1127, Brain Res. 2003, vol. 985: 113-126). MSNs are classified into two groups: the MSN that express D dopam ine receptors responsible for a direct (striatonigral) pathway and the MSN that express D dopamine receptors responsible for an indirect (striatopallidal) pathway. The function of direct pathway is to plan and execution, while indirect path way is to act as a brake on behavioral activation. As PDE10A expresses in both MSNs, PDE10A inhibitors could activate both of these pathways. The antipsychotic efficacy of current 0009 was also disclosed in WO2008/001182 Pamphlet. US 2012/0277430 A1 Nov. 1, 2012 I0059) R' is a hydrogen atom, or a methyl group, and 0090 8 0060 Ra is a hydrogen atom, or a Cacyclic hydrocar 0091. The compound according to any one of the above mentioned 1 to 7, wherein bon group which can be substituted, a compound of formula: 0092 R represents 0093 a hydrogenatom, or a Coalkoxy group which can be substituted. 0094. 9 0.095 The compound according to any one of the above mentioned 1 to 8, wherein (0096 R represents 0097 a hydrogen atom, or a Coalkoxy group. 0.098 (10) 0099. The compound according to any one of the above mentioned 1 to 9), wherein 0100 R represents 0101 a hydrogen atom. 01.02 11 0061 wherein 0103) The compound according to any one of the above 0062 Ring A" is a benzene ring which can be substituted mentioned 1 to 10, wherein by halogen, and 0104 Ring. A represents 0063 R'" is an acyl group 0105 a benzene ring which can be substituted by 1 to 5 0064 are excluded: substituents selected from 0065 or a salt thereof. 0106 (1) a halogen atom, 0107 (2) a Co alkyl group which can be substituted, 0.066 (2) 0.108 (3) a Coalkoxy group which can be substituted, 0067. The compound according to the above-mentioned 0109 (4) a 4- to 6-membered heterocyclic group contain 1 or 2, wherein ing 0 or 1 oxygenatom, and 1 to 3 nitrogen atoms as heteroa 0068 R represents toms which can be substituted, 0069 a halogen atom, a hydroxy group, a Co alkyl 0110 (5) a C- alkylsulfonyl group which can be substi group which can be substituted, or a Co to alkoxy group tuted, which can be substituted. I0111 (6) a C-, cycloalkyl group which can be substituted, 0070 (3) 0112 (7) a cyano group, 0071. The compound according to the above-mentioned 0113 (8) a carbamoyl group which can be substituted, 1 or 2, wherein 0114 (9) a Co alkylsulfonyloxy group which can be 0072 R represents substituted, 0073 a Coalkoxy group which can be substituted by 0115 (10) a C-7 cycloalkyl-C alkynyl group which can one or more Substituents selected from a halogen atom, a be substituted, Coalkoxy group, and a C-7 cycloalkyl group. 0116 (11) a tetrahydropyranyl group which can be substi 0074 (4) tuted, 0075.
Load more

Recommended publications
  • Novel Antagonists for the Human Adenosine
    UvA-DARE (Digital Academic Repository) Novel antagonists for the human adenosine A2A and A3 receptor via purine nitration: synthesis and biological evaluation of C2-substituted 6- trifluoromethylpurines and 1-deazapurines Koch, M. Publication date 2011 Document Version Final published version Link to publication Citation for published version (APA): Koch, M. (2011). Novel antagonists for the human adenosine A2A and A3 receptor via purine nitration: synthesis and biological evaluation of C2-substituted 6-trifluoromethylpurines and 1- deazapurines. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam (https://dare.uva.nl) Download date:05 Oct 2021 Novel antagonists for the human adenosine A Novel antagonists for the human adenosine Uitnodiging Novel antagonists for the voor het bijwonen van human adenosine de openbare verdediging van het proefschrift van A2A and A3 receptor via purine nitration Melle Koch op vrijdag 21 oktober 2011 om 14:00 uur in de Agnietenkapel van de Universiteit van Amsterdam Synthesis and biological evaluation Oudezijds Voorburgwal 231 of C2-substituted te Amsterdam 2A Na afloop van de promotie and A 6-trifluoromethylpurines zal hier tevens de receptie .
    [Show full text]
  • 1,3-Oxazolidin-2-One Derivatives Useeful As Cetp Inhibitors
    (19) TZZ Z Z_T (11) EP 2 029 560 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: C07D 263/22 (2006.01) C07D 413/04 (2006.01) 24.04.2013 Bulletin 2013/17 C07D 413/10 (2006.01) C07D 417/10 (2006.01) C07D 417/14 (2006.01) A61K 31/421 (2006.01) (2006.01) (2006.01) (21) Application number: 06849136.4 A61K 31/422 A61K 31/427 A61K 31/443 (2006.01) A61P 9/00 (2006.01) (22) Date of filing: 29.12.2006 (86) International application number: PCT/US2006/049494 (87) International publication number: WO 2007/079186 (12.07.2007 Gazette 2007/28) (54) 1,3-OXAZOLIDIN-2-ONE DERIVATIVES USEEFUL AS CETP INHIBITORS 1,3-OXAZOLIDIN-2-ON-DERIVATIVE, DIE ZUR VERWENDUNG ALS CETP-INHIBITOREN GEEIGNET SIND DERIVES DE 1,3-OXAZOLIDIN-2-ONE EN TANT QU’INHIBITEURS DE CETP (84) Designated Contracting States: • SINCLAIR, Peter, J. AT BE BG CH CY CZ DE DK EE ES FI FR GB GR Rahway, New Jersey 07065-0907 (US) HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI • CHEN, Yi-Heng SK TR Rahway, New Jersey 07065-0907 (US) • SMITH, Cameron, J. (30) Priority: 30.12.2005 US 755284 P Rahway, New Jersey 07065-0907 (US) • LI, Hong (43) Date of publication of application: Rahway, New Jersey 07065-0907 (US) 04.03.2009 Bulletin 2009/10 (74) Representative: Hussain, Deeba (73) Proprietor: Merck Sharp & Dohme Corp. Merck & Co., Inc. Rahway, NJ 07065-0907 (US) Patent Department Hertford Road (72) Inventors: Hoddesdon • ALI, Amjad Hertfordshire EN11 9BU (GB) Rahway, New Jersey 07065-0907 (US) • LU, Zhijian (56) References cited: Rahway, New Jersey 07065-0907 (US) EP-A1- 0 294 995 EP-A1- 0 605 729 WO-A-2006/014413 Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations.
    [Show full text]
  • "This Is the Peer Reviewed Version of the Following Article: [Drug and Alcohol Review, 2019, 38 (5), Pp
    "This is the peer reviewed version of the following article: [Drug and Alcohol Review, 2019, 38 (5), pp. 465 - 472], which has been published in final form at [https://doi.org/10.1111/dar.12958] This article may be used for non‐commercial purposes in accordance with Wiley Terms and Conditions for Self‐Archiving Harmless? A hierarchical analysis of poppers use correlates among young gay and bisexual men Daniel Demant, PhDa,b* & Oscar Oviedo-Trespalacios, PhDc a Lecturer, Australian Centre for Public and Population Health Research, Faculty of Health, University of Technology Sydney, Ultimo, Australia b Visiting Fellow, School of Public Health and Social Work, Faculty of Health, Queensland University of Technology (QUT), Brisbane, Australia c Research Fellow, Centre for Accident Research and Road Safety-Queensland (CARRS-Q), Institute of Health and Biomedical Innovation (IHBI), Faculty of Health, Queensland University of Technology (QUT), Brisbane, Australia *Corresponding Author Dr Daniel Demant Lecturer in Public Health Australian Centre for Public and Population Health Research Faculty of Health University of Technology Sydney 235-253 Jones Street, Ultimo, New South Wales 2007, Australia Tel: +61 02 9514 5499 Email: [email protected] ORCiD Daniel Demant: 0000-0003-3330-2972 Oscar Oviedo-Trespalacios: 0000-0001-5916-3996 Running title: Poppers use among young gay and bisexual men Abstract Introduction: Poppers (alkyl nitrites) are recreational substances commonly used during sexual activity. The current legal status of poppers is complex and wide-ranging bans are increasingly under discussion. Research has identified disproportionate levels of poppers use in sexual minority men. While research on poppers use among sexual minority men exists, little is known about poppers use patterns and correlations with psycho-social and other factors among gay and bisexual young men.
    [Show full text]
  • US5489610.Pdf
    |||||||| US00548961OA United States Patent 19 11 Patent Number: 5,489,610 Fung et al. 45) Date of Patent: 8 Feb. 6, 1996 54 SUSTAINED RELEASE ORGANIC NITRITE 58 Field of Search .................................... 514/506, 509, THERAPY 514/645, 740 75 Inventors: Ho-Leung Fung, Getzville; John A. 56) References Cited Bauer, Williamsville, both of N.Y. U.S. PATENT DOCUMENTS 73 Assignee: Research Foundation of the State 5,278,192 l/1994 Fung et al. .............................. 514f645 University of New York, Albany, N.Y. OTHER PUBLICATIONS * Notice: The portion of the term of this patent Derwent Abstracts 78–35053A, "Medicaments for Treating disclaimed.subsequent to Jan. 11, 2011, has been Cardiardiogenic Shock”, Fribolinis is et al. (1978). Patent Abstracts of Japan, vol. 12, No. 467, Dec. 7, 1988, 21 Appl. No.: 199,280 "Tape Preparation'. 22, PCT Filed: Jun. 30, 1993 Primary Examiner-Frederick Krass Attorney, Agent, or Firm-Kirschstein et al. 86 PCT No.: PCT/US93/06235 (57) ABSTRACT S371 Date: Mar. 1, 1994 A method of treating a patient suffering from a condition S 102(e) Date: Mar. 1, 1994 requiring vasodilator therapy, comprising long term, con 87 PCT Pub. No.: WO94/01103 tinuous adminstration of an organic nitrite to the patient in a dosage form capable of delivering a sufficient therapeutic PCT Pub. Date:Jan. 20, 1994 amount of nitrite to the bloodstream of the patient thereby providing effective vasodilator therapy for at least 24 hours Related U.S. Application Data without the development of tolerance in the patient. The a method of the invention is useful in treating conditions such 63 Continuation-in-part of Ser.
    [Show full text]
  • II.1.8 Alkyl Nitrites by Yasuo Seto
    1.8 II.1.8 Alkyl nitrites by Yasuo Seto Introduction Alkyl nitrites are highly volatile organic solvents of aliphatic alcohol esters of nitrites [1]. Amyl nitritea, butyl nitrite and isobutyl nitrite are the representative alkyl nitrites; their boiling points are 98, 78 and 67 °C, respectively. Amyl nitrite is being widely used as a detoxicant for cyanide poisoning, because alkyl nitrites oxidize hemoglobin in erythrocytes to yield methemogloblin, which is bound with cyanide to inactivate it [1]. Alkyl nitrites also show a coronary artery-di- lating eff ect, and had been, therefore, used for the treatment of angina pectoris many years ago [2]; the pharmacological eff ect of the dilation of the coronary arteries was found due to the action of nitrogen monoxide produced by decomposition of alkyl nitrites [3]. Th ey are being mainly used as materials for manufacturing drugs or as reagents for synthesis in industries; they are also used as aromatics. Because of their pharmacological eff ect, alkyl nitrites are being abused as uncontrolled inhalant drugs and causing a social problem [4]. Although there are many reports on toxic and fatal cases due to alkyl nitrites [5], reports on their fatal doses are few; it is estimated that oral ingestion of 10–15 mL of each alkyl nitrite causes serious methe- moglobinemia [6]. Th e LD50 value for an alkyl nitrite is reported to be 205 mg/kg. Th ere are not many cases of analysis of alkyl nitrites in the fi eld of forensic toxicology. In this chapter, the methods for analysis of the compounds by headspace (HS)-gas chromatography (GC) and liquid-liquid extraction-GC are presented.
    [Show full text]
  • 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
    [Show full text]
  • An Ordinance of the City of Cameron, Clinton And
    Bill 2014-46 Ordinance 5852 AN ORDINANCE OF THE CITY OF CAMERON, CLINTON AND DeKALB COUNTIES, MISSOURI, CREATING SECTIONS 8-4.6 THROUGH 8-4.6b REGARDING THE INHALATION OF SOLVENTS TO ARTICLE I - IN GENERAL, OF CHAPTER 8 – OFFENSES MISCELLANEOUS OF THE CITY OF CAMERON CODE WHEREAS , the purposeful inhalation of solvents to cause symptoms of intoxication and euphoria is a serious health risk; and WHEREAS , the State of Missouri has passed legislation dealing with this issue at the state level as well as creating charge codes available for local/ordinance violations. NOW, THEREFORE, BE IT ORDAINED BY THE CITY COUNCIL OF THE CITY OF CAMERON, CLINTON AND DeKALB COUNTIES, MISSOURI AS FOLLOWS: Section 1. The Mayor and City Council are hereby authorized to create Sections 8-4.6 through 8-4.6b as follows: Sec. 8-4.6 Inhalation or inducing others to inhale solvent fumes to cause certain reactions, prohibited - exceptions. No person shall intentionally smell or inhale the fumes or any solvent, particularly toluol, amyl nitrite, butyl nitrite, cyclohexyl nitrite, ethyl nitrite, pentyl nitrite and propyl nitrite and their iso-analogues or induce any other person to do so for the purpose of causing a condition of, or inducing symptoms of, intoxication, elation, euphoria, dizziness, excitement, irrational behavior, exhilaration, paralysis, stupefaction, or dulling of senses or nervous system, or for the purpose of, in any manner, changing, distorting or disturbing the audio, visual or mental processes; except that this Section shall not apply to the inhalation of any anesthesia for medical or dental purposes. (State law reference – Similar provisions, RSMo 578.250) Sec.
    [Show full text]
  • 3.2.2 Table B: List of Dangerous Goods in Alphabetical Order the Following
    Copyright © United Nations, 2008 3.2.2 Table B: List of dangerous goods in alphabetical order The following Table B is an alphabetical list of the substances and articles which are listed in the UN numerical order in Table A of 3.2.1. It does not form an integral part of ADN. It has been prepared, with all necessary care by the Secretariat of the United Nations Economic Commission for Europe, in order to facilitate the consultation of Annexes A and B, but it cannot be relied upon as a substitute for the careful study and observance of the actual provisions of those annexed Regulations which, in case of conflict, are deemed to be authoritative. NOTE 1: For the purpose of determining the alphabetical order the following information has been ignored, even when it forms part of the proper shipping name: numbers; Greek letters; the abbreviations "sec" and "tert"; and the letters "N" (nitrogen), "n" (normal), "o" (ortho) "m" (meta), "p" (para) and "N.O.S." (not otherwise specified). NOTE 2: The name of a substance or article in block capital letters indicates a proper shipping name (see 3.1.2). NOTE 3: The name of a substance or article in block capital letters followed by the word "see" indicates an alternative proper shipping name or part of a proper shipping name (except for PCBs) (see 3.1.2.1). NOTE 4: An entry in lower case letters followed by the word "see" indicates that the entry is not a proper shipping name; it is a synonym. NOTE 5: Where an entry is partly in block capital letters and partly in lower case letters, the latter part is considered not to be part of the proper shipping name (see 3.1.2.1).
    [Show full text]
  • Poppers‘ Products and Analytical Detectability of a Single Use of ‘Poppers‘
    Toxichem Krimtech 2015;82(Special Issue):218 Analysis of ‘poppers‘ products and analytical detectability of a single use of ‘poppers‘ Susanne Vogt*, Verena Angerer, Jürgen Kempf, Volker Auwärter Universitätsklinikum Freiburg, Institut für Rechtsmedizin, Forensische Toxikologie, Albert- straße 9, D–79104 Freiburg; *corresponding author: [email protected] Aims: Alkyl nitrites, also known as ‘poppers’, have a long history as medical drugs and ’aph- rodisiacs’. Typical effects include vasodilation, hypotension, methaemoglobinaemia and re- duction of smooth muscle tonus. To our knowledge analytical verification of ‘poppers’ use by detection of the corresponding alcohols was only described in post mortem cases so far. We aimed to develop a method for detection of a modest ‘poppers’ dose and apply it to samples taken after inhalation of “Rush Ultra Strong” containing isopropyl, isobutyl, n-pentyl and 2- methylbutyl nitrite. In addition, several ‘poppers’ products were analysed to determine their ingredients. Methods: Analysis was performed on a Clarus gas chromatograph using a capil- lary column (RTX®-502.2, Restek, 60 m, 0.53 mm ID, 3 µm film thickness) fitted with a headspace autosampler and a flame ionisation detector. Carrier gas was H2 at a flow rate of 45 mL/min. A split flow of 10 mL/min was applied for analysis of body fluids, to analyse the pure nitrites and ‘poppers’ products the split flow was increased. Results: 76 different ‘pop- pers’ flasks were analysed. In 51.3 % of the products the declared contents differed from the analytical results. After modest use of ‘poppers’ 2-Methyl-1-butanol could be detected in the first 3 serum samples.
    [Show full text]
  • Hazardous Waste List (California Code of Regulations, Title 22 Section 66261.126)
    Hazardous Waste List (California Code of Regulations, Title 22 Section 66261.126) Appendix X - List of Chemical Names and Common Names for Hazardous Wastes and Hazardous Materials (a) This subdivision sets forth a list of chemicals which create a presumption that a waste is a hazardous waste. If a waste consists of or contains a chemical listed in this subdivision, the waste is presumed to be a hazardous waste Environmental Regulations of CALIFORNIA unless it is determined that the waste is not a hazardous waste pursuant to the procedures set forth in section 66262.11. The hazardous characteristics which serve as a basis for listing the chemicals are indicated in the list as follows: (X) toxic (C) corrosive (I) ignitable (R) reactive * =Extremely Hazardous A chemical denoted with an asterisk is presumed to be an extremely hazardous waste unless it does not exhibit any of the criteria set forth in section 66261.110 and section 66261.113. Trademark chemical names are indicated by all capital letters. 1. Acetaldehyde (X,I) 2. Acetic acid (X,C,I) 3. Acetone, Propanone (I) 4. *Acetone cyanohydrin (X) 5. Acetonitrile (X,I) 6. *2-Acetylaminofluorene, 2-AAF (X) 7. Acetyl benzoyl peroxide (X,I,R) 8. *Acetyl chloride (X,C,R) 9. Acetyl peroxide (X,I,R) 10. Acridine (X) 11. *Acrolein, Aqualin (X,I) 12. *Acrylonitrile (X,I) 13. *Adiponitrile (X) 14. *Aldrin; 1,2,3,4,10,10-Hexachloro-1,4,4a,5,8,8a-hexahydro-1,4,5,8-endo-exodimethanonaphthlene (X) 15. *Alkyl aluminum chloride (C,I,R) 16. *Alkyl aluminum compounds (C,I,R) 17.
    [Show full text]
  • Isopentyl Nitrite
    Isopentyl nitrite sc-215197 Material Safety Data Sheet Hazard Alert Code Key: EXTREME HIGH MODERATE LOW Section 1 - CHEMICAL PRODUCT AND COMPANY IDENTIFICATION PRODUCT NAME Isopentyl nitrite STATEMENT OF HAZARDOUS NATURE CONSIDERED A HAZARDOUS SUBSTANCE ACCORDING TO OSHA 29 CFR 1910.1200. NFPA FLAMMABILITY3 HEALTH2 HAZARD INSTABILITY2 SUPPLIER Santa Cruz Biotechnology, Inc. 2145 Delaware Avenue Santa Cruz, California 95060 800.457.3801 or 831.457.3800 EMERGENCY: ChemWatch Within the US & Canada: 877-715-9305 Outside the US & Canada: +800 2436 2255 (1-800-CHEMCALL) or call +613 9573 3112 SYNONYMS C5-H11-NO2, (CH3)2CHCH2CH2ONO, amilnitrit, "amyl nitrit", "amyl nitrite", "iso-pentyl nitrite", "3-methylbutanol nitrite", "3-methylbutyl nitrite", "nitrous acid, 3-methylbutyl ester", Aspiral, IPN, Nitramyl, Vaporole Section 2 - HAZARDS IDENTIFICATION CHEMWATCH HAZARD RATINGS Min Max Flammability: 3 Toxicity: 2 Body Contact: 2 Min/Nil=0 Low=1 Reactivity: 1 Moderate=2 High=3 Chronic: 0 Extreme=4 CANADIAN WHMIS SYMBOLS 1 of 7 EMERGENCY OVERVIEW RISK Harmful by inhalation and if swallowed. Irritating to eyes and skin. Highly flammable. POTENTIAL HEALTH EFFECTS ACUTE HEALTH EFFECTS SWALLOWED ! Accidental ingestion of the material may be harmful; animal experiments indicate that ingestion of less than 150 gram may be fatal or may produce serious damage to the health of the individual. EYE ! This material can cause eye irritation and damage in some persons. SKIN ! This material can cause inflammation of the skin oncontact in some persons. ! The material may accentuate any pre-existing dermatitis condition. ! Skin contact with the material may damage the health of the individual; systemic effects may result following absorption.
    [Show full text]
  • 1 Synthesis of C-2 and C-6 Functionalized
    1 SYNTHESIS OF C-2 AND C-6 FUNCTIONALIZED RIBOFURANOSYLPURINE ANALOGUES AS POTENTIAL ANTIVIRAL AGENTS TARGETING INHIBITION OF INOSINE MONOPHOSPHATE DEHYDROGENASE. by Eric Osei-Tutu Bonsu (Under the Direction of Vasu Nair) ABSTRACT IMPDH is a key enzyme in the de novo biosynthesis of purine nucleotides. It catalyzes the conversion of inosine monophosphate (IMP) to xanthosine monophosphate (XMP) using NAD as a cofactor. XMP is successively converted to deoxyguanosine triphosphate (substrate for DNA synthesis) by GMP synthetase, phosphorylating enzymes and ribonucleotide reductase. IMPDH exists in two isoforms, type I and type II. These isoforms have the same size and share 84% homology. The type I isoform is expressed in both normal and rapidly proliferating cells, whereas type II is preferentially upregulated in proliferating cells. Inhibition of IMPDH has anticancer, antiviral, antibacterial and immunosuppressive effects. Three inhibitors of IMPDH are currently in clinical use: ribavirin (a broad spectrum antiviral), mizoribine (immunosuppressant used in Japan) and mycophenolic mofetil (prodrug of mycophenolic acid, US approved immunosuppressant). None of these inhibitors possess significant selectivity against the type II isoform over the type I, hence there are severe side effects. The quest for specific isozyme inhibitors led to the discovery of the potential antiviral activity of certain C-2 functionalized hypoxanthine and C-2, C-6 modified purine systems against HSV1, HSV2, VV, VSV and RSV. 2 Nair and coworkers have synthesized similar congeners, including 2-vinylinosine (broad spectrum antiviral), which is active due to its C-2 vinyl moiety acting as a Michael Acceptor. This dissertation elucidates the design and synthesis of new Michael Acceptor-type nucleosides.
    [Show full text]