Known Bioactives Library: Prestwick 2 Collection
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(12) United States Patent (10) Patent No.: US 9,498,481 B2 Rao Et Al
USOO9498481 B2 (12) United States Patent (10) Patent No.: US 9,498,481 B2 Rao et al. (45) Date of Patent: *Nov. 22, 2016 (54) CYCLOPROPYL MODULATORS OF P2Y12 WO WO95/26325 10, 1995 RECEPTOR WO WO99/O5142 2, 1999 WO WOOO/34283 6, 2000 WO WO O1/92262 12/2001 (71) Applicant: Apharaceuticals. Inc., La WO WO O1/922.63 12/2001 olla, CA (US) WO WO 2011/O17108 2, 2011 (72) Inventors: Tadimeti Rao, San Diego, CA (US); Chengzhi Zhang, San Diego, CA (US) OTHER PUBLICATIONS Drugs of the Future 32(10), 845-853 (2007).* (73) Assignee: Auspex Pharmaceuticals, Inc., LaJolla, Tantry et al. in Expert Opin. Invest. Drugs (2007) 16(2):225-229.* CA (US) Wallentin et al. in the New England Journal of Medicine, 361 (11), 1045-1057 (2009).* (*) Notice: Subject to any disclaimer, the term of this Husted et al. in The European Heart Journal 27, 1038-1047 (2006).* patent is extended or adjusted under 35 Auspex in www.businesswire.com/news/home/20081023005201/ U.S.C. 154(b) by Od en/Auspex-Pharmaceuticals-Announces-Positive-Results-Clinical M YW- (b) by ayS. Study (published: Oct. 23, 2008).* This patent is Subject to a terminal dis- Concert In www.concertpharma. com/news/ claimer ConcertPresentsPreclinicalResultsNAMS.htm (published: Sep. 25. 2008).* Concert2 in Expert Rev. Anti Infect. Ther. 6(6), 782 (2008).* (21) Appl. No.: 14/977,056 Springthorpe et al. in Bioorganic & Medicinal Chemistry Letters 17. 6013-6018 (2007).* (22) Filed: Dec. 21, 2015 Leis et al. in Current Organic Chemistry 2, 131-144 (1998).* Angiolillo et al., Pharmacology of emerging novel platelet inhibi (65) Prior Publication Data tors, American Heart Journal, 2008, 156(2) Supp. -
Metabolic-Hydroxy and Carboxy Functionalization of Alkyl Moieties in Drug Molecules: Prediction of Structure Influence and Pharmacologic Activity
molecules Review Metabolic-Hydroxy and Carboxy Functionalization of Alkyl Moieties in Drug Molecules: Prediction of Structure Influence and Pharmacologic Activity Babiker M. El-Haj 1,* and Samrein B.M. Ahmed 2 1 Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, University of Science and Technology of Fujairah, Fufairah 00971, UAE 2 College of Medicine, Sharjah Institute for Medical Research, University of Sharjah, Sharjah 00971, UAE; [email protected] * Correspondence: [email protected] Received: 6 February 2020; Accepted: 7 April 2020; Published: 22 April 2020 Abstract: Alkyl moieties—open chain or cyclic, linear, or branched—are common in drug molecules. The hydrophobicity of alkyl moieties in drug molecules is modified by metabolic hydroxy functionalization via free-radical intermediates to give primary, secondary, or tertiary alcohols depending on the class of the substrate carbon. The hydroxymethyl groups resulting from the functionalization of methyl groups are mostly oxidized further to carboxyl groups to give carboxy metabolites. As observed from the surveyed cases in this review, hydroxy functionalization leads to loss, attenuation, or retention of pharmacologic activity with respect to the parent drug. On the other hand, carboxy functionalization leads to a loss of activity with the exception of only a few cases in which activity is retained. The exceptions are those groups in which the carboxy functionalization occurs at a position distant from a well-defined primary pharmacophore. Some hydroxy metabolites, which are equiactive with their parent drugs, have been developed into ester prodrugs while carboxy metabolites, which are equiactive to their parent drugs, have been developed into drugs as per se. -
ELECTRONIC CLAIMS MANAGEMENT ENGINE (ECME) Version 1.0
ELECTRONIC CLAIMS MANAGEMENT ENGINE (ECME) Version 1.0 USER MANUAL December 2020 Department of Veterans Affairs Office of Information and Technology (OIT) Product Development Revision History Date Description (Patch # if applicable) Project Manager Technical Writer 12/2020 Updated for BPS*1*27 MCCF EDI TAS MCCF EDI TAS Updated Potential Secondary Rx Claims Report ePharmacy ePharmacy Screen Display Development TeamDevelopment Team Updated Title Page date and footers 04/2020 Updated for BPS*1*26 REDACTED REDACTED Updated section 5.6 Add/View Comments Updated Title Page date and footers 1/2019 Updated for BPS*1*24 REDACTED REDACTED Change label on Claim Log, Modify Change View (CV), Enhance Claim Reports 08/2018 Updated for BPS*1*23 REDACTED REDACTED Update Title page date, footer date Modification filter questions CV Change View action, Rx Activity Log to add Date of Service to ECME Log, Resubmit with Edits action, Process Secondary/TRICARE Rx to ECME option, Payable Claims Report, Rejected Claims Report, Reversal Claims Report, Claims Submitted Not Yet Released Report, Recent Transactions Report, Closed Claims Report, View ePharmacy Rx Report Option 11/2017 Updated for BPS*1*22 REDACTED REDACTED Update Title page date, modification to Change View action; change auto-reverse parameter and auto-reversal bulletin; add Facility ID Qualifier and Reconciliation ID to Claim Log and Claim Response Inquiry; add new action PR Print Reports to VER View ePharmacy Rx. 05/2017 Updated for BPS*1*21 REDACTED REDACTED 08/2016 Updated for BPS*1*20 REDACTED -
COMBINED LIST of Particularly Hazardous Substances
COMBINED LIST of Particularly Hazardous Substances revised 2/4/2021 IARC list 1 are Carcinogenic to humans list compiled by Hector Acuna, UCSB IARC list Group 2A Probably carcinogenic to humans IARC list Group 2B Possibly carcinogenic to humans If any of the chemicals listed below are used in your research then complete a Standard Operating Procedure (SOP) for the product as described in the Chemical Hygiene Plan. Prop 65 known to cause cancer or reproductive toxicity Material(s) not on the list does not preclude one from completing an SOP. Other extremely toxic chemicals KNOWN Carcinogens from National Toxicology Program (NTP) or other high hazards will require the development of an SOP. Red= added in 2020 or status change Reasonably Anticipated NTP EPA Haz list COMBINED LIST of Particularly Hazardous Substances CAS Source from where the material is listed. 6,9-Methano-2,4,3-benzodioxathiepin, 6,7,8,9,10,10- hexachloro-1,5,5a,6,9,9a-hexahydro-, 3-oxide Acutely Toxic Methanimidamide, N,N-dimethyl-N'-[2-methyl-4-[[(methylamino)carbonyl]oxy]phenyl]- Acutely Toxic 1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (Methyl-CCNU) Prop 65 KNOWN Carcinogens NTP 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) IARC list Group 2A Reasonably Anticipated NTP 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) (Lomustine) Prop 65 1-(o-Chlorophenyl)thiourea Acutely Toxic 1,1,1,2-Tetrachloroethane IARC list Group 2B 1,1,2,2-Tetrachloroethane Prop 65 IARC list Group 2B 1,1-Dichloro-2,2-bis(p -chloropheny)ethylene (DDE) Prop 65 1,1-Dichloroethane -
Upregulation of Peroxisome Proliferator-Activated Receptor-Α And
Upregulation of peroxisome proliferator-activated receptor-α and the lipid metabolism pathway promotes carcinogenesis of ampullary cancer Chih-Yang Wang, Ying-Jui Chao, Yi-Ling Chen, Tzu-Wen Wang, Nam Nhut Phan, Hui-Ping Hsu, Yan-Shen Shan, Ming-Derg Lai 1 Supplementary Table 1. Demographics and clinical outcomes of five patients with ampullary cancer Time of Tumor Time to Age Differentia survival/ Sex Staging size Morphology Recurrence recurrence Condition (years) tion expired (cm) (months) (months) T2N0, 51 F 211 Polypoid Unknown No -- Survived 193 stage Ib T2N0, 2.41.5 58 F Mixed Good Yes 14 Expired 17 stage Ib 0.6 T3N0, 4.53.5 68 M Polypoid Good No -- Survived 162 stage IIA 1.2 T3N0, 66 M 110.8 Ulcerative Good Yes 64 Expired 227 stage IIA T3N0, 60 M 21.81 Mixed Moderate Yes 5.6 Expired 16.7 stage IIA 2 Supplementary Table 2. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of an ampullary cancer microarray using the Database for Annotation, Visualization and Integrated Discovery (DAVID). This table contains only pathways with p values that ranged 0.0001~0.05. KEGG Pathway p value Genes Pentose and 1.50E-04 UGT1A6, CRYL1, UGT1A8, AKR1B1, UGT2B11, UGT2A3, glucuronate UGT2B10, UGT2B7, XYLB interconversions Drug metabolism 1.63E-04 CYP3A4, XDH, UGT1A6, CYP3A5, CES2, CYP3A7, UGT1A8, NAT2, UGT2B11, DPYD, UGT2A3, UGT2B10, UGT2B7 Maturity-onset 2.43E-04 HNF1A, HNF4A, SLC2A2, PKLR, NEUROD1, HNF4G, diabetes of the PDX1, NR5A2, NKX2-2 young Starch and sucrose 6.03E-04 GBA3, UGT1A6, G6PC, UGT1A8, ENPP3, MGAM, SI, metabolism -
A TWO-YEAR RETROSPECTIVE ANALYSIS of ADVERSE DRUG REACTIONS with 5PSQ-031 FLUOROQUINOLONE and QUINOLONE ANTIBIOTICS 24Th Congress Of
A TWO-YEAR RETROSPECTIVE ANALYSIS OF ADVERSE DRUG REACTIONS WITH 5PSQ-031 FLUOROQUINOLONE AND QUINOLONE ANTIBIOTICS 24th Congress of V. Borsi1, M. Del Lungo2, L. Giovannetti1, M.G. Lai1, M. Parrilli1 1 Azienda USL Toscana Centro, Pharmacovigilance Centre, Florence, Italy 2 Dept. of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), 27-29 March 2019 Section of Pharmacology and Toxicology , University of Florence, Italy BACKGROUND PURPOSE On 9 February 2017, the Pharmacovigilance Risk Assessment Committee (PRAC) initiated a review1 of disabling To review the adverse drugs and potentially long-lasting side effects reported with systemic and inhaled quinolone and fluoroquinolone reactions (ADRs) of antibiotics at the request of the German medicines authority (BfArM) following reports of long-lasting side effects systemic and inhaled in the national safety database and the published literature. fluoroquinolone and quinolone antibiotics that MATERIAL AND METHODS involved peripheral and central nervous system, Retrospective analysis of ADRs reported in our APVD involving ciprofloxacin, flumequine, levofloxacin, tendons, muscles and joints lomefloxacin, moxifloxacin, norfloxacin, ofloxacin, pefloxacin, prulifloxacin, rufloxacin, cinoxacin, nalidixic acid, reported from our pipemidic given systemically (by mouth or injection). The period considered is September 2016 to September Pharmacovigilance 2018. Department (PVD). RESULTS 22 ADRs were reported in our PVD involving fluoroquinolone and quinolone antibiotics in the period considered and that affected peripheral or central nervous system, tendons, muscles and joints. The mean patient age was 67,3 years (range: 17-92 years). 63,7% of the ADRs reported were serious, of which 22,7% caused hospitalization and 4,5% caused persistent/severe disability. 81,8% of the ADRs were reported by a healthcare professional (physician, pharmacist or other) and 18,2% by patient or a non-healthcare professional. -
Equimax & Eraquell Oral Gel for Horses
Equimax & Eraquell Oral Gel for Horses Annual Wormer Pack [active ingredients: Ivermectin & Praziquantel] (POM-VPS) Revised AN Equimax Oral Gel for Horses January 2013 01009/2012 Eraquell Oral Gel for Horses December 2015 01163/2015 Page 1 of 15 SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE VETERINARY MEDICINAL PRODUCT Equimax Oral Gel for Horses 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each gram of Equimax contains Active substances Ivermectin ........................................................ 18.7 mg Praziquantel ..................................................... 140.3 mg Excipients Titanium dioxide (E171) ................................... 20 mg Propylene glycol ............................................... 731 mg For a full list of excipents, see section 6.1 3. PHARMACEUTICAL FORM Oral gel. 4. CLINICAL PARTICULARS 4.1 Target species Horses. 4.2 Indications for use, specifying the target species For the treatment of mixed cestode and nematode or arthropod infestations, due to adult and immature roundworms, lungworms, bots and tapeworms in horses: Nematodes Large-strongyle: Strongylus vulgaris (adult and arterial larvae) Strongylus edentatus (adult and L4 tissue larval stages) Strongylus equinus (adult) Triodontophorus spp. (adult) Small-strongyle: Cyathostomum: Cylicocyclus spp., Cylicostephanus spp., Cylicodontophorus spp., Gyalocephalus spp. (adult and non-inhibited mucosal larvae). Parascaris: Parascaris equorum (adult and larvae). Page 2 of 15 Oxyuris: Oxyuris equi (larvae). Trichostrongylus:Trichostrongylus -
Programme & Abstracts
The 57th Annual Meeting of the International Association of Forensic Toxicologists. 2nd - 6th September 2019 BIRMINGHAM, UK The ICC Birmingham Broad Street, Birmingham B1 2EA Programme & Abstracts 1 Thank You to our Sponsors PlatinUm Gold Silver Bronze 2 3 Contents Welcome message 5 Committees 6 General information 7 iCC maps 8 exhibitors list 10 Exhibition Hall 11 Social Programme 14 opening Ceremony 15 Schedule 16 Oral Programme MONDAY 2 September 19 TUESDAY 3 September 21 THURSDAY 5 September 28 FRIDAY 6 September 35 vendor Seminars 42 Posters 46 oral abstracts 82 Poster abstracts 178 4 Welcome Message It is our great pleasure to welcome you to TIAFT Gala Dinner at the ICC on Friday evening. On the accompanying pages you will see a strong the UK for the 57th Annual Meeting of scientific agenda relevant to modern toxicology and we The International Association of Forensic thank all those who submitted an abstract and the Toxicologists Scientific Committees for making the scientific programme (TIAFT) between 2nd and 6th a success. Starting with a large Young Scientists September 2019. Symposium and Dr Yoo Memorial plenary lecture by Prof Tony Moffat on Monday, there are oral session topics in It has been decades since the Annual Meeting has taken Clinical & Post-Mortem Toxicology on Tuesday, place in the country where TIAFT was founded over 50 years Human Behaviour Toxicology & Drug-Facilitated Crime on ago. The meeting is supported by LTG (London Toxicology Thursday and Toxicology in Sport, New Innovations and Group) and the UKIAFT (UK & Ireland Association of Novel Research & Employment/Occupational Toxicology Forensic Toxicologists) and we thank all our exhibitors and on Friday. -
Zebrafish Behavioral Profiling Links Drugs to Biological Targets and Rest/Wake Regulation
www.sciencemag.org/cgi/content/full/327/5963/348/DC1 Supporting Online Material for Zebrafish Behavioral Profiling Links Drugs to Biological Targets and Rest/Wake Regulation Jason Rihel,* David A. Prober, Anthony Arvanites, Kelvin Lam, Steven Zimmerman, Sumin Jang, Stephen J. Haggarty, David Kokel, Lee L. Rubin, Randall T. Peterson, Alexander F. Schier* *To whom correspondence should be addressed. E-mail: [email protected] (A.F.S.); [email protected] (J.R.) Published 15 January 2010, Science 327, 348 (2010) DOI: 10.1126/science.1183090 This PDF file includes: Materials and Methods SOM Text Figs. S1 to S18 Table S1 References Supporting Online Material Table of Contents Materials and Methods, pages 2-4 Supplemental Text 1-7, pages 5-10 Text 1. Psychotropic Drug Discovery, page 5 Text 2. Dose, pages 5-6 Text 3. Therapeutic Classes of Drugs Induce Correlated Behaviors, page 6 Text 4. Polypharmacology, pages 6-7 Text 5. Pharmacological Conservation, pages 7-9 Text 6. Non-overlapping Regulation of Rest/Wake States, page 9 Text 7. High Throughput Behavioral Screening in Practice, page 10 Supplemental Figure Legends, pages 11-14 Figure S1. Expanded hierarchical clustering analysis, pages 15-18 Figure S2. Hierarchical and k-means clustering yield similar cluster architectures, page 19 Figure S3. Expanded k-means clustergram, pages 20-23 Figure S4. Behavioral fingerprints are stable across a range of doses, page 24 Figure S5. Compounds that share biological targets have highly correlated behavioral fingerprints, page 25 Figure S6. Examples of compounds that share biological targets and/or structural similarity that give similar behavioral profiles, page 26 Figure S7. -
)&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 -
Histamine Receptors
Tocris Scientific Review Series Tocri-lu-2945 Histamine Receptors Iwan de Esch and Rob Leurs Introduction Leiden/Amsterdam Center for Drug Research (LACDR), Division Histamine is one of the aminergic neurotransmitters and plays of Medicinal Chemistry, Faculty of Sciences, Vrije Universiteit an important role in the regulation of several (patho)physiological Amsterdam, De Boelelaan 1083, 1081 HV, Amsterdam, The processes. In the mammalian brain histamine is synthesised in Netherlands restricted populations of neurons that are located in the tuberomammillary nucleus of the posterior hypothalamus.1 Dr. Iwan de Esch is an assistant professor and Prof. Rob Leurs is These neurons project diffusely to most cerebral areas and have full professor and head of the Division of Medicinal Chemistry of been implicated in several brain functions (e.g. sleep/ the Leiden/Amsterdam Center of Drug Research (LACDR), VU wakefulness, hormonal secretion, cardiovascular control, University Amsterdam, The Netherlands. Since the seventies, thermoregulation, food intake, and memory formation).2 In histamine receptor research has been one of the traditional peripheral tissues, histamine is stored in mast cells, eosinophils, themes of the division. Molecular understanding of ligand- basophils, enterochromaffin cells and probably also in some receptor interaction is obtained by combining pharmacology specific neurons. Mast cell histamine plays an important role in (signal transduction, proliferation), molecular biology, receptor the pathogenesis of various allergic conditions. After mast cell modelling and the synthesis and identification of new ligands. degranulation, release of histamine leads to various well-known symptoms of allergic conditions in the skin and the airway system. In 1937, Bovet and Staub discovered compounds that antagonise the effect of histamine on these allergic reactions.3 Ever since, there has been intense research devoted towards finding novel ligands with (anti-) histaminergic activity. -
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.