Annex 2A Peru Tariff Schedule See General Notes for Staging Explanation
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INVESTIGATION of NATURAL PRODUCT SCAFFOLDS for the DEVELOPMENT of OPIOID RECEPTOR LIGANDS by Katherine M
INVESTIGATION OF NATURAL PRODUCT SCAFFOLDS FOR THE DEVELOPMENT OF OPIOID RECEPTOR LIGANDS By Katherine M. Prevatt-Smith Submitted to the graduate degree program in Medicinal Chemistry and the Graduate Faculty of the University of Kansas in partial fulfillment of the requirements for the degree of Doctor of Philosophy. _________________________________ Chairperson: Dr. Thomas E. Prisinzano _________________________________ Dr. Brian S. J. Blagg _________________________________ Dr. Michael F. Rafferty _________________________________ Dr. Paul R. Hanson _________________________________ Dr. Susan M. Lunte Date Defended: July 18, 2012 The Dissertation Committee for Katherine M. Prevatt-Smith certifies that this is the approved version of the following dissertation: INVESTIGATION OF NATURAL PRODUCT SCAFFOLDS FOR THE DEVELOPMENT OF OPIOID RECEPTOR LIGANDS _________________________________ Chairperson: Dr. Thomas E. Prisinzano Date approved: July 18, 2012 ii ABSTRACT Kappa opioid (KOP) receptors have been suggested as an alternative target to the mu opioid (MOP) receptor for the treatment of pain because KOP activation is associated with fewer negative side-effects (respiratory depression, constipation, tolerance, and dependence). The KOP receptor has also been implicated in several abuse-related effects in the central nervous system (CNS). KOP ligands have been investigated as pharmacotherapies for drug abuse; KOP agonists have been shown to modulate dopamine concentrations in the CNS as well as attenuate the self-administration of cocaine in a variety of species, and KOP antagonists have potential in the treatment of relapse. One drawback of current opioid ligand investigation is that many compounds are based on the morphine scaffold and thus have similar properties, both positive and negative, to the parent molecule. Thus there is increasing need to discover new chemical scaffolds with opioid receptor activity. -
Discovery of Small Molecule and Peptide-Based Ligands for the Methyl-Lysine Binding Proteins 53Bp1 and Phf1/Phf19
DISCOVERY OF SMALL MOLECULE AND PEPTIDE-BASED LIGANDS FOR THE METHYL-LYSINE BINDING PROTEINS 53BP1 AND PHF1/PHF19 Michael Thomas Perfetti A dissertation submitted to the faculty of the University of North Carolina at Chapel Hill in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Division of Chemical Biology and Medicinal Chemistry in the Doctoral Program of the UNC Eshelman School of Pharmacy. Chapel Hill 2015 Approved by: Stephen Frye David Lawrence Albert Bowers Brian Strahl Greg Gang Wang Andrew Lee © 2015 Michael Thomas Perfetti ALL RIGHTS RESERVED ii ABSTRACT Michael Thomas Perfetti: Discovery of Small Molecule and Peptide-based Ligands for the Methyl-Lysine Binding Proteins 53BP1 and PHF1/PHF19 (Under the direction of Stephen V. Frye) Improving the understanding of the role of chromatin regulators in the initiation, development, and suppression of cancer and other devastating diseases is critical, as they are integral players in the regulation of DNA integrity and gene expression. Developing chemical tools for histone binding proteins that possess cellular activity will allow for further elucidation of the specific function of this class of histone regulating proteins. This research specifically targeted two different classes of Tudor domain containing histone binding proteins that are directly involved in the DNA damage response and modulation of gene transcription activities. The first methyl-lysine binding protein targeted was 53BP1, which is a DNA damage response protein. 53BP1 uses a tandem tudor domain (TTD) to recognize histone H4 dimethylated on lysine 20 (H4K20me2), a post-translational modification (PTM) induced by double-strand DNA breaks. -
01012100 Pure-Bred Horses 0 0 0 0 0 01012900 Lives Horses, Except
AR BR UY Mercosu PY applied NCM Description applied applied applied r Final Comments tariff tariff tariff tariff Offer 01012100 Pure-bred horses 0 0 0 0 0 01012900 Lives horses, except pure-bred breeding 2 2 2 2 0 01013000 Asses, pure-bred breeding 4 4 4 4 4 01019000 Asses, except pure-bred breeding 4 4 4 4 4 01022110 Purebred breeding cattle, pregnant or lactating 0 0 0 0 0 01022190 Other pure-bred cattle, for breeding 0 0 0 0 0 Other bovine animals for breeding,pregnant or 01022911 lactating 2 2 2 2 0 01022919 Other bovine animals for breeding 2 2 2 2 4 01022990 Other live catlle 2 2 2 2 0 01023110 Pure-bred breeding buffalo, pregnant or lactating 0 0 0 0 0 01023190 Other pure-bred breeding buffalo 0 0 0 0 0 Other buffalo for breeding, ex. pure-bred or 01023911 pregnant 2 2 2 2 0 Other buffalo for breeding, except pure-bred 01023919 breeding 2 2 2 2 4 01023990 Other buffalos 2 2 2 2 0 01029000 Other live animals of bovine species 0 0 0 0 0 01031000 Pure-bred breedig swines 0 0 0 0 0 01039100 Other live swine, weighing less than 50 kg 2 2 2 2 0 01039200 Other live swine, weighing 50 kg or more 2 2 2 2 0 01041011 Pure-bred breeding, pregnant or lactating, sheep 0 0 0 0 0 01041019 Other pure-bred breeding sheep 0 0 0 0 0 01041090 Others live sheep 2 2 2 2 0 01042010 Pure-bred breeding goats 0 0 0 0 0 01042090 Other live goats 2 2 2 2 0 Fowls spec.gallus domestic.w<=185g pure-bred 01051110 breeding 0 0 0 0 0 Oth.live fowls spec.gall.domest.weig.not more than 01051190 185g 2 2 2 2 0 01051200 Live turkeys, weighing not more than 185g 2 2 -
Synthesis of Isothiocyanates Using DMT/NMM/Tso− As a New Desulfurization Reagent
molecules Article Synthesis of Isothiocyanates Using DMT/NMM/TsO− as a New Desulfurization Reagent Łukasz Janczewski 1,* , Dorota Kr˛egiel 2 and Beata Kolesi ´nska 1 1 Faculty of Chemistry, Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland; [email protected] 2 Department of Environmental Biotechnology, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Wolczanska 171/173, 90-924 Lodz, Poland; [email protected] * Correspondence: [email protected] Abstract: Thirty-three alkyl and aryl isothiocyanates, as well as isothiocyanate derivatives from esters of coded amino acids and from esters of unnatural amino acids (6-aminocaproic, 4-(aminomethyl)benzoic, and tranexamic acids), were synthesized with satisfactory or very good yields (25–97%). Synthesis was performed in a “one-pot”, two-step procedure, in the presence of organic base (Et3N, DBU or NMM), and carbon disulfide via dithiocarbamates, with 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4- methylmorpholinium toluene-4-sulfonate (DMT/NMM/TsO−) as a desulfurization reagent. For the synthesis of aliphatic and aromatic isothiocyanates, reactions were carried out in a microwave reactor, and selected alkyl isothiocyanates were also synthesized in aqueous medium with high yields (72–96%). Isothiocyanate derivatives of L- and D-amino acid methyl esters were synthesized, under conditions without microwave radiation assistance, with low racemization (er 99 > 1), and their absolute configuration was confirmed by circular dichroism. Isothiocyanate derivatives of natural and unnatural amino acids were evaluated for antibacterial activity on E. coli and S. aureus bacterial strains, where the Citation: Janczewski, Ł.; Kr˛egiel,D.; most active was ITC 9e. -
Pharmacy and Poisons (Third and Fourth Schedule Amendment) Order 2017
Q UO N T FA R U T A F E BERMUDA PHARMACY AND POISONS (THIRD AND FOURTH SCHEDULE AMENDMENT) ORDER 2017 BR 111 / 2017 The Minister responsible for health, in exercise of the power conferred by section 48A(1) of the Pharmacy and Poisons Act 1979, makes the following Order: Citation 1 This Order may be cited as the Pharmacy and Poisons (Third and Fourth Schedule Amendment) Order 2017. Repeals and replaces the Third and Fourth Schedule of the Pharmacy and Poisons Act 1979 2 The Third and Fourth Schedules to the Pharmacy and Poisons Act 1979 are repealed and replaced with— “THIRD SCHEDULE (Sections 25(6); 27(1))) DRUGS OBTAINABLE ONLY ON PRESCRIPTION EXCEPT WHERE SPECIFIED IN THE FOURTH SCHEDULE (PART I AND PART II) Note: The following annotations used in this Schedule have the following meanings: md (maximum dose) i.e. the maximum quantity of the substance contained in the amount of a medicinal product which is recommended to be taken or administered at any one time. 1 PHARMACY AND POISONS (THIRD AND FOURTH SCHEDULE AMENDMENT) ORDER 2017 mdd (maximum daily dose) i.e. the maximum quantity of the substance that is contained in the amount of a medicinal product which is recommended to be taken or administered in any period of 24 hours. mg milligram ms (maximum strength) i.e. either or, if so specified, both of the following: (a) the maximum quantity of the substance by weight or volume that is contained in the dosage unit of a medicinal product; or (b) the maximum percentage of the substance contained in a medicinal product calculated in terms of w/w, w/v, v/w, or v/v, as appropriate. -
Opioid Receptorsreceptors
OPIOIDOPIOID RECEPTORSRECEPTORS defined or “classical” types of opioid receptor µ,dk and . Alistair Corbett, Sandy McKnight and Graeme Genes encoding for these receptors have been cloned.5, Henderson 6,7,8 More recently, cDNA encoding an “orphan” receptor Dr Alistair Corbett is Lecturer in the School of was identified which has a high degree of homology to Biological and Biomedical Sciences, Glasgow the “classical” opioid receptors; on structural grounds Caledonian University, Cowcaddens Road, this receptor is an opioid receptor and has been named Glasgow G4 0BA, UK. ORL (opioid receptor-like).9 As would be predicted from 1 Dr Sandy McKnight is Associate Director, Parke- their known abilities to couple through pertussis toxin- Davis Neuroscience Research Centre, sensitive G-proteins, all of the cloned opioid receptors Cambridge University Forvie Site, Robinson possess the same general structure of an extracellular Way, Cambridge CB2 2QB, UK. N-terminal region, seven transmembrane domains and Professor Graeme Henderson is Professor of intracellular C-terminal tail structure. There is Pharmacology and Head of Department, pharmacological evidence for subtypes of each Department of Pharmacology, School of Medical receptor and other types of novel, less well- Sciences, University of Bristol, University Walk, characterised opioid receptors,eliz , , , , have also been Bristol BS8 1TD, UK. postulated. Thes -receptor, however, is no longer regarded as an opioid receptor. Introduction Receptor Subtypes Preparations of the opium poppy papaver somniferum m-Receptor subtypes have been used for many hundreds of years to relieve The MOR-1 gene, encoding for one form of them - pain. In 1803, Sertürner isolated a crystalline sample of receptor, shows approximately 50-70% homology to the main constituent alkaloid, morphine, which was later shown to be almost entirely responsible for the the genes encoding for thedk -(DOR-1), -(KOR-1) and orphan (ORL ) receptors. -
The Effects of Low Dose Lysergic Acid Diethylamide Administration in a Rodent Model of Delay Discounting
Western Michigan University ScholarWorks at WMU Dissertations Graduate College 6-2020 The Effects of Low Dose Lysergic Acid Diethylamide Administration in a Rodent Model of Delay Discounting Robert J. Kohler Western Michigan University, [email protected] Follow this and additional works at: https://scholarworks.wmich.edu/dissertations Part of the Biological Psychology Commons Recommended Citation Kohler, Robert J., "The Effects of Low Dose Lysergic Acid Diethylamide Administration in a Rodent Model of Delay Discounting" (2020). Dissertations. 3565. https://scholarworks.wmich.edu/dissertations/3565 This Dissertation-Open Access is brought to you for free and open access by the Graduate College at ScholarWorks at WMU. It has been accepted for inclusion in Dissertations by an authorized administrator of ScholarWorks at WMU. For more information, please contact [email protected]. THE EFFECTS OF LOW DOSE LYSERGIC ACID DIETHYLAMIDE ADMINISTRATION IN A RODENT MODEL OF DELAY DISCOUNTING by Robert J. Kohler A dissertation submitted to the Graduate College In partial fulfillment of the requirements for the degree of Doctor of Philosophy Psychology Western Michigan University June 2020 Doctoral Committee: Lisa Baker, Ph.D., Chair Anthony DeFulio, Ph.D. Cynthia Pietras, Ph.D. John Spitsbergen, Ph.D. Copyright by Robert J. Kohler 2020 THE EFFECTS OF LOW DOSE LYSERGIC ACID DIETHYLAMIDE ADMINISTRATION IN A RODENT MODEL OF DELAY DISCOUNTING Robert J. Kohler, Ph.D. Western Michigan University, 2020 The resurgence of Lysergic Acid Diethylamide (LSD) as a therapeutic tool requires a revival in research, both basic and clinical, to bridge gaps in knowledge left from a previous generation of work. Currently, no study has been published with the intent of establishing optimal microdose concentrations of LSD in an animal model. -
Specificity of the Antibody Receptor Site to D-Lysergamide
Proc. Nat. Acad. Sci. USA Vol. 68, No. 7, pp. 1483-1487, July 1971 Specificity of the Antibody Receptor Site to D-Lysergamide: Model of a Physiological Receptor for Lysergic Acid Diethylamide (molecular structure/hallucinogenic/rabbit/guinea pig/psychotomimetic) HELEN VAN VUNAKIS, JOHN T. FARROW, HILDA B. GJIKA, AND LAWRENCE LEVINE Graduate Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02154 Commnunicated by Francis 0. Schmitt, April 21, 1971 ABSTRACT Antibodies to D-lysergic acid have been amine, and NN-dimethyl-3,4,5-trimethoxyphenylethylamine produced in rabbits and guinea pigs and a radioimmuno- were the generous gifts of Dr. W. E. Scott of Hoffmann-La assay for the hapten was developed. The specificity of this Iysergamide-antilysergamide reaction was determined by Roche. DOM (2,5-dimethoxy-4-methylamphetamine) was competitive binding with unlabeled lysergic acid diethyl- given to us by Dr. S. H. Snyder of Johns Hopkins Univer- amnide (LSD), psychotomimetic drugs, neurotransmitters, sity. Sandoz Pharmaceuticals provided us with ergonovine, and other compounds with diverse structures. LSD and methylergonovine, ergosine, and ergotomine. LSD tartarate several related ergot alkaloids were potent competitors, three to seven times more potent than lysergic acid itself. powder (Sandoz Batch no. 98601) and psilocybin powder The NN-dimethyl derivatives of several compounds, in- (Sandoz Batch no. 55001) were provided by the U.S. Food and cluding tryptamine, 5-hydroxytryptamine, 4-hydroxy- Drug Administration and the National Institute of Mental tryptamine, 5-methoxytryptamine, tyramine, and mesca- Health. line, were only about ten times less effective than lysergic Psilocin was obtained by dephosphorylating psilocybin acid, even though these compounds lack some of the ring systems of lysergic acid. -
Annex 2B Tariff Schedule of the United States See General Notes to Annex 2B for Staging Explanation HTSUS No
Annex 2B Tariff Schedule of the United States See General Notes to Annex 2B for Staging Explanation HTSUS No. Description Base Rate Staging 0101 Live horses, asses, mules and hinnies: 0101.10.00 -Purebred breeding animals Free E 0101.90 -Other: 0101.90.10 --Horses Free E 0101.90.20 --Asses 6.8% B --Mules and hinnies: 0101.90.30 ---Imported for immediate slaughter Free E 0101.90.40 ---Other 4.5% A 0102 Live bovine animals: 0102.10.00 -Purebred breeding animals Free E 0102.90 -Other: 0102.90.20 --Cows imported specially for dairy purposes Free E 0102.90.40 --Other 1 cent/kg A 0103 Live swine: 0103.10.00 -Purebred breeding animals Free E -Other: 0103.91.00 --Weighing less than 50 kg each Free E 0103.92.00 --Weighing 50 kg or more each Free E 0104 Live sheep and goats: 0104.10.00 -Sheep Free E 0104.20.00 -Goats 68 cents/head A 0105 Live poultry of the following kinds: Chickens, ducks, geese, turkeys and guineas: -Weighing not more than 185 g: 0105.11.00 --Chickens 0.9 cents each A 0105.12.00 --Turkeys 0.9 cents each A 0105.19.00 --Other 0.9 cents each A -Other: 0105.92.00 --Chickens, weighing not more than 2,000 g 2 cents/kg A 0105.93.00 --Chickens, weighing more than 2,000 g 2 cents/kg A 0105.99.00 --Other 2 cents/kg A 0106 Other live animals: -Mammals: 0106.11.00 --Primates Free E 0106.12.00 --Whales, dolphins and porpoises (mammals of the order Cetacea); manatees and dugongs (mammals of the order Sirenia) Free E 0106.19 --Other: 2B-Schedule-1 HTSUS No. -
Larry Kramer Interview Number
A PROGRAM OF MIX – THE NEW YORK LESBIAN & GAY EXPERIMENTAL FILM FESTIVAL Interviewee: Larry Kramer Interview Number: 035 Interviewer: Sarah Schulman Date of Interview: November 15, 2003 © 2004 The New York Lesbian & Gay Experimental Film Festival, Inc. ACT UP ORAL HISTORY PROJECT Interview of Larry Kramer November 15, 2003 Tape I 00:07:00 SARAH SCHULMAN: If you could say your name, how old you are, where we are and today’s date? LARRY KRAMER: My name is Larry Kramer. We are in my study, in my lover’s and my house in New Preston, Connecticut. SS: How old are you? LK: I’m 68. SS: Mazel tov. What’s today’s date? LK: That I’ve lasted this long is a major miracle. SS: And today is? LK: November 15th, 2003. SS: Well, Larry, you’ve been interviewed many times and you have a lot to say, and what we really want to do is ask you the questions that you probably have not repeated ad nauseum before and that, maybe, more of an internal conversation from people who were inside ACT UP together. So we’re not going to be asking you these generic questions or things that anybody who is interested can find other places. I just want to ask you a few background questions. When did you family come to this country? LK: My father was born in this country, and his mother was from Russia and no one knows where his father was from. And my mother came when she was four, also from Russia. -
Phencyclidine: an Update
Phencyclidine: An Update U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES • Public Health Service • Alcohol, Drug Abuse and Mental Health Administration Phencyclidine: An Update Editor: Doris H. Clouet, Ph.D. Division of Preclinical Research National Institute on Drug Abuse and New York State Division of Substance Abuse Services NIDA Research Monograph 64 1986 DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Alcohol, Drug Abuse, and Mental Health Administratlon National Institute on Drug Abuse 5600 Fishers Lane Rockville, Maryland 20657 For sale by the Superintendent of Documents, U.S. Government Printing Office Washington, DC 20402 NIDA Research Monographs are prepared by the research divisions of the National lnstitute on Drug Abuse and published by its Office of Science The primary objective of the series is to provide critical reviews of research problem areas and techniques, the content of state-of-the-art conferences, and integrative research reviews. its dual publication emphasis is rapid and targeted dissemination to the scientific and professional community. Editorial Advisors MARTIN W. ADLER, Ph.D. SIDNEY COHEN, M.D. Temple University School of Medicine Los Angeles, California Philadelphia, Pennsylvania SYDNEY ARCHER, Ph.D. MARY L. JACOBSON Rensselaer Polytechnic lnstitute National Federation of Parents for Troy, New York Drug Free Youth RICHARD E. BELLEVILLE, Ph.D. Omaha, Nebraska NB Associates, Health Sciences Rockville, Maryland REESE T. JONES, M.D. KARST J. BESTEMAN Langley Porter Neuropsychiatric lnstitute Alcohol and Drug Problems Association San Francisco, California of North America Washington, D.C. DENISE KANDEL, Ph.D GILBERT J. BOTV N, Ph.D. College of Physicians and Surgeons of Cornell University Medical College Columbia University New York, New York New York, New York JOSEPH V. -
Etorphine to Rat-Brain Homogenate (Opiate Receptor/Morphine/Antagonist) ERIC J
Proc. Nat. Acad. Sci. USA Vol. 70, No. 7, pp. 1947-1949, July 1973 Stereospecific Binding of the Potent Narcotic Analgesic [31H]Etorphine to Rat-Brain Homogenate (opiate receptor/morphine/antagonist) ERIC J. SIMON, JACOB M. HILLER, AND IRIT EDELMAN Department of Medicine, New York University Medical Center, New York, N.Y. 10016 Communicated by Michael Heidelberger, April 19, 1973 ABSTRACT Etorphine, the most potent narcotic anal- The present report provides further support for the exis- gesic known, was labeled with tritium by catalytic ex- tence of and furnishes change. This drug exhibits stereospecific, saturable bind- opiate receptors evidence that stable ing to rat-brain homogenate. At saturation, the stereo- binding to receptors is not an exclusive property of antago- specific binding is 0.1-0.15 pmol/mg of protein. Specific nists. We report several new properties of the receptors and binding is inhibited by high salt concentrations, sulfhydryl some differences from the results reported for naloxone bind- reagents, and proteolytic enzymes, but is unaffected by ing. phospholipases A and C, sodium azide, sodium fluoride, and prostaglandins El and E2. Competition for binding of MATERIALS AND METHODS [3Hletorphine correlates with agonist and antagonist po- tencies. The stable, stereospecific binding of an active Materials. Etorphine was purchased from American Cyan- narcotic analgesic supports the existence of opiate recep- amide. Levorphanol and dextrorphan were generously tors. donated by Hoffman-LaRoche, Inc., morphine and nalorphine Specific receptors for opiates in the central nervous system by Merck & Co., naloxone by Endo Laboratories, and metha- have been postulated for many years, based primarily on the done by Eli Lily.