In Search of a Generic Chiral Strategy: 101 Separations with One Method
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1 Abietic Acid R Abrasive Silica for Polishing DR Acenaphthene M (LC
1 abietic acid R abrasive silica for polishing DR acenaphthene M (LC) acenaphthene quinone R acenaphthylene R acetal (see 1,1-diethoxyethane) acetaldehyde M (FC) acetaldehyde-d (CH3CDO) R acetaldehyde dimethyl acetal CH acetaldoxime R acetamide M (LC) acetamidinium chloride R acetamidoacrylic acid 2- NB acetamidobenzaldehyde p- R acetamidobenzenesulfonyl chloride 4- R acetamidodeoxythioglucopyranose triacetate 2- -2- -1- -β-D- 3,4,6- AB acetamidomethylthiazole 2- -4- PB acetanilide M (LC) acetazolamide R acetdimethylamide see dimethylacetamide, N,N- acethydrazide R acetic acid M (solv) acetic anhydride M (FC) acetmethylamide see methylacetamide, N- acetoacetamide R acetoacetanilide R acetoacetic acid, lithium salt R acetobromoglucose -α-D- NB acetohydroxamic acid R acetoin R acetol (hydroxyacetone) R acetonaphthalide (α)R acetone M (solv) acetone ,A.R. M (solv) acetone-d6 RM acetone cyanohydrin R acetonedicarboxylic acid ,dimethyl ester R acetonedicarboxylic acid -1,3- R acetone dimethyl acetal see dimethoxypropane 2,2- acetonitrile M (solv) acetonitrile-d3 RM acetonylacetone see hexanedione 2,5- acetonylbenzylhydroxycoumarin (3-(α- -4- R acetophenone M (LC) acetophenone oxime R acetophenone trimethylsilyl enol ether see phenyltrimethylsilyl... acetoxyacetone (oxopropyl acetate 2-) R acetoxybenzoic acid 4- DS acetoxynaphthoic acid 6- -2- R 2 acetylacetaldehyde dimethylacetal R acetylacetone (pentanedione -2,4-) M (C) acetylbenzonitrile p- R acetylbiphenyl 4- see phenylacetophenone, p- acetyl bromide M (FC) acetylbromothiophene 2- -5- -
Quinolizidine-Derived Lucanthone and Amitriptyline Analogues Endowed with Potent Antileishmanial Activity
pharmaceuticals Article Quinolizidine-Derived Lucanthone and Amitriptyline Analogues Endowed with Potent Antileishmanial Activity Michele Tonelli 1,* , Anna Sparatore 2,* , Nicoletta Basilico 3,* , Loredana Cavicchini 3, Silvia Parapini 4 , Bruno Tasso 1 , Erik Laurini 5 , Sabrina Pricl 5,6 , Vito Boido 1 and Fabio Sparatore 1 1 Dipartimento di Farmacia, Università degli Studi di Genova, Viale Benedetto XV, 3, 16132 Genova, Italy; [email protected] (B.T.); [email protected] (V.B.); [email protected] (F.S.) 2 Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milano, Italy 3 Dipartimento di Scienze Biomediche Chirurgiche e Odontoiatriche, Università degli Studi di Milano, Via Pascal 36, 20133 Milano, Italy; [email protected] 4 Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Via Mangiagalli 31, 20133 Milano, Italy; [email protected] 5 Molecular Biology and Nanotechnology Laboratory (MolBNL@UniTS), DEA, Piazzale Europa 1, 34127 Trieste, Italy; [email protected] (E.L.); [email protected] (S.P.) 6 Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland * Correspondence: [email protected] (M.T.); [email protected] (A.S.); [email protected] (N.B.) Received: 4 October 2020; Accepted: 21 October 2020; Published: 25 October 2020 Abstract: Leishmaniases are neglected diseases that are endemic in many tropical and sub-tropical Countries. Therapy is based on different classes of drugs which are burdened by severe side effects, occurrence of resistance and high costs, thereby creating the need for more efficacious, safer and inexpensive drugs. -
N-Alkylamino Derivates of Aromatic, Tricyclic Compounds in the Treatment of Drug-Resistant Protozoal Infections
Europaisches Patentamt 0 338 532 European Patent Office Qv Publication number: A2 Office europeen des brevets EUROPEAN PATENT APPLICATION 31/54 © Application number: 89107027.8 © mt.ci.4.A61K 31/38 , A61K @ Date of filing: 19.04.89 © Priority: 20.04.88 US 183858 © Applicant: MERRELL DOW 12.09.88 US 243524 PHARMACEUTICALS INC. 2110 East Galbraith Road @. Date of publication of application: Cincinnati Ohio 45215-6300(US) 25.10.89 Bulletin 89/43 © Inventor: Bitonti, Alan J. © Designated Contracting States: 7854 Carraway Court AT BE CH DE ES FR GB GR IT LI LU NL SE Maineville Ohio 45039(US) Inventor: McCann, Peter P. 3782 Cooper Road Cincinnati Ohio 45241 (US) Inventor: Sjoerdsma, Albert 5475 Waring Drive Cincinnati Ohio 45243(US) © Representative: Vossius & Partner Siebertstrasse 4 P.O. Box 86 07 67 D-8000 Munchen 86(DE) © N-alkylamino derivates of aromatic, tricyclic compounds in the treatment of drug-resistant protozoal infections. © Drug-resistant protozoal infection, particularly, drug-resistant malarial infection in humans, can be effectively treated with standard antiprotozoal agents if administered in conjunction with a tricyclic N-aminoalkyi iminodiben- zyl, dibenzylcycloheptane and cycloheptene, phenothiazine, dibenzoxazepine, dibenzoxepine, or thioxanthene derivative. CM < CM CO in oo CO CO LU Xerox Copy Centre EP 0 338 532 A2 N-ALKYLAMINO DERIVATIVES OF AROMATIC, TRICYCLIC COMPOUNDS IN THE TREATMENT OF DRUG- RESISTANT PROTOZOAL INFECTIONS This invention relates to the use of certain N-(aminoalkyl) derivatives of iminodibenzyl, dibenzyl- cycioheptane and cycloheptene, phenothiazine, dibenzoxazepine, dibenzoxepine, and thioxanthene in the treatment of drug-resistant malaria and in the treatment of other drug-resistant protozoal infections. -
The Organic Chemistry of Drug Synthesis
THE ORGANIC CHEMISTRY OF DRUG SYNTHESIS VOLUME 3 DANIEL LEDNICER Analytical Bio-Chemistry Laboratories, Inc. Columbia, Missouri LESTER A. MITSCHER The University of Kansas School of Pharmacy Department of Medicinal Chemistry Lawrence, Kansas A WILEY-INTERSCIENCE PUBLICATION JOHN WILEY AND SONS New York • Chlchester • Brisbane * Toronto • Singapore Copyright © 1984 by John Wiley & Sons, Inc. All rights reserved. Published simultaneously in Canada. Reproduction or translation of any part of this work beyond that permitted by Section 107 or 108 of the 1976 United States Copyright Act without the permission of the copyright owner is unlawful. Requests for permission or further information should be addressed to the Permissions Department, John Wiley & Sons, Inc. Library of Congress Cataloging In Publication Data: (Revised for volume 3) Lednicer, Daniel, 1929- The organic chemistry of drug synthesis. "A Wiley-lnterscience publication." Includes bibliographical references and index. 1. Chemistry, Pharmaceutical. 2. Drugs. 3. Chemistry, Organic—Synthesis. I. Mitscher, Lester A., joint author. II. Title. [DNLM 1. Chemistry, Organic. 2. Chemistry, Pharmaceutical. 3. Drugs—Chemical synthesis. QV 744 L473o 1977] RS403.L38 615M9 76-28387 ISBN 0-471-09250-9 (v. 3) Printed in the United States of America 10 907654321 With great pleasure we dedicate this book, too, to our wives, Beryle and Betty. The great tragedy of Science is the slaying of a beautiful hypothesis by an ugly fact. Thomas H. Huxley, "Biogenesis and Abiogenisis" Preface Ihe first volume in this series represented the launching of a trial balloon on the part of the authors. In the first place, wo were not entirely convinced that contemporary medicinal (hemistry could in fact be organized coherently on the basis of organic chemistry. -
United States Patent Office Patented June 10, 1969
3,449,427 United States Patent Office Patented June 10, 1969 2 l optical isomers. Unless otherwise specified in the descrip 3,449,427 AMINOCYCLOPROPANE DERVATIVES OF tion and accompanying claims, it is intended to include all 5H-DIBENZOadCYCLOHEPTENES isomers, whether separated or mixtures thereof. Carl Kaiser, Haddon Heights, N.J., and Charles L. Zirkle, The novel aminocyclopropane derivatives of 5H-di Berwin, Pa., assignors to Smith Kline & French Labora benzoadcycloheptenes of this invention are prepared tories, Philadelphia, Pa., a corporation of Pennsylvania by several methods, the choice of which depending on the No Drawing. Filed June 3, 1965, Ser. No. 461,176 definitions of m, n, R1 and R2. The starting materials for Int. CI. C07c87/28, 91/16, 149/42 these methods are generally 5H-dibenzo(a,d)cyclohep U.S. C. 260-570.8 8 Claims tenes having the formula: O ABSTRACT OF THE DISCLOSURE Y\ 5[2-(N-N di substituted amino) cyclopropyl)-10,11-di R hydro 5H dibenzo(a,d)cycloheptanes are prepared via the amides and acids. The compounds are antidepressants, 5 X transquillizers and anorectics. H Formula II This invention relates to novel aminocyclopropane de in which Y and R are as defined in Formula I. These rivatives of 5H-dibenzoadcycloheptenes having useful 20 compounds are prepared by reduction of the correspond pharmacodynamic activity. More specifically, the com ing 5H-dibenzo(a,d)cyclohepten-5-ones with, for example, pounds of this invention have central nervous system sodium in a lower alkanol, preferably, ethanol or by the activity such as antidepressant, tranquilizing and anorectic Wolff-Kishner method. -
University of Groningen Chiroptical Molecular Switches De Lange
University of Groningen Chiroptical molecular switches de Lange, Ben IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2006 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): de Lange, B. (2006). Chiroptical molecular switches: synthesis and applications. s.n. Copyright Other than for strictly personal use, 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), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date: 26-09-2021 CHAPTER 5 NON-CHIRQL STERICALLY OVERCROWDED ALKENES Temperature dependent NMR measurements have been successfully applied to obtain thermal isomerization barriers of chiral sterically overcrowded bistricyclic ethylenes functionalized with different bridging groups in the lower and upper part, which could not be resolved into their enantiomers via HPLC, as shown in the -
Sodium Channel Na Channels;Na+ Channels
Sodium Channel Na channels;Na+ channels Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na +) through a cell's plasma membrane. They are classified according to the trigger that opens the channel for such ions, i.e. either a voltage-change (Voltage-gated, voltage-sensitive, or voltage-dependent sodium channel also called VGSCs or Nav channel) or a binding of a substance (a ligand) to the channel (ligand-gated sodium channels). In excitable cells such as neurons, myocytes, and certain types of glia, sodium channels are responsible for the rising phase of action potentials. Voltage-gated Na+ channels can exist in any of three distinct states: deactivated (closed), activated (open), or inactivated (closed). Ligand-gated sodium channels are activated by binding of a ligand instead of a change in membrane potential. www.MedChemExpress.com 1 Sodium Channel Inhibitors & Modulators (+)-Kavain (-)-Sparteine sulfate pentahydrate Cat. No.: HY-B1671 ((-)-Lupinidine (sulfate pentahydrate)) Cat. No.: HY-B1304 Bioactivity: (+)-Kavain, a main kavalactone extracted from Piper Bioactivity: (-)-Sparteine sulfate pentahydrate ((-)-Lupinidine sulfate methysticum, has anticonvulsive properties, attenuating pentahydrate) is a class 1a antiarrhythmic agent and a sodium vascular smooth muscle contraction through interactions with channel blocker. It is an alkaloid, can chelate the bivalents voltage-dependent Na + and Ca 2+ channels [1]. (+)-Kav… calcium and magnesium. Purity: 99.98% Purity: 98.0% Clinical Data: No Development Reported Clinical Data: Launched Size: 10mM x 1mL in DMSO, Size: 10mM x 1mL in DMSO, 5 mg, 10 mg 50 mg A-803467 Ajmaline Cat. No.: HY-11079 (Cardiorythmine; (+)-Ajmaline) Cat. No.: HY-B1167 Bioactivity: A 803467 is a selective Nav1.8 sodium channel blocker with an Bioactivity: Ajmaline is an alkaloid that is class Ia antiarrhythmic agent. -
Trimeprazine Increases IRS2 in Human Islets and Promotes Pancreatic Β Cell Growth and Function in Mice
Trimeprazine increases IRS2 in human islets and promotes pancreatic β cell growth and function in mice Alexandra Kuznetsova, … , Arun Sharma, Morris F. White JCI Insight. 2016;1(3):e80749. https://doi.org/10.1172/jci.insight.80749. Research Article Endocrinology Metabolism The capacity of pancreatic β cells to maintain glucose homeostasis during chronic physiologic and immunologic stress is important for cellular and metabolic homeostasis. Insulin receptor substrate 2 (IRS2) is a regulated adapter protein that links the insulin and IGF1 receptors to downstream signaling cascades. Since strategies to maintain or increase IRS2 expression can promote β cell growth, function, and survival, we conducted a screen to find small molecules that can increase IRS2 mRNA in isolated human pancreatic islets. We identified 77 compounds, including 15 that contained a tricyclic core. To establish the efficacy of our approach, one of the tricyclic compounds, trimeprazine tartrate, was investigated in isolated human islets and in mouse models. Trimeprazine is a first-generation antihistamine that acts as a partial agonist against the histamine H1 receptor (H1R) and other GPCRs, some of which are expressed on human islets. Trimeprazine promoted CREB phosphorylation and increased the concentration of IRS2 in islets. IRS2 was required for trimeprazine to increase nuclear Pdx1, islet mass, β cell replication and function, and glucose tolerance in mice. Moreover, trimeprazine synergized with anti-CD3 Abs to reduce the progression of diabetes in NOD mice. Finally, it increased the function of human islet transplants in streptozotocin-induced (STZ-induced) diabetic mice. Thus, trimeprazine, its analogs, or possibly other compounds that increase IRS2 in islets and β cells without […] Find the latest version: https://jci.me/80749/pdf RESEARCH ARTICLE Trimeprazine increases IRS2 in human islets and promotes pancreatic β cell growth and function in mice Alexandra Kuznetsova,1 Yue Yu,1 Jennifer Hollister-Lock,2 Lynn Opare-Addo,1 Aldo Rozzo,1 Marianna Sadagurski,1 Lisa Norquay,1 Jessica E. -
United States Patent Office Patented Aug
3,524,000 United States Patent Office Patented Aug. 11, 1970 2 3,524,000 pounds with the substantial absence of significant toxic ANTHELMINTC COMPOSITIONS AND effects. Still another object is to provide a method for METHOD OF USING SAME treating helminthiasis with tricyclic compounds together John R. Egerton, Neshanic Station, and Joseph Di Netta, With anthelmintically active 2-substituted benzimidazoles Watchung, N.J., assignors to Merck & Co., Inc., Rah wherein the tricyclic compounds enhance the activity of way, N.J., a corporation of New Jersey the benzimidazoles. These and other objects will appear No Drawing. Continuation-in-part of application Ser. No. from the detailed description which follows. 439,926, Mar. 15, 1965. This application Oct. 20, 1967, According to the present invention, it has been sur Ser. No. 676,697 Int, C.A01n 9/22 A61d 7/00 A61k27/00 prisingly discovered that the anthelmintic activity of 2-sub O stituted benzimidazoles can be greatly enhanced when the U.S. C. 424-267 13 Claims benzimidazole is administered to the host animal in the presence of certain classes of tricyclic compounds. Thus, in one of its preferred aspects, the invention provides ABSTRACT OF THE DISCLOSURE novel 2-component compositions wherein one component The anthelmintic activity of 2-substituted benzimida is at least one of certain tricyclic compounds and the zoles is greatly enhanced when the benzimidazole is ad other component is at least one anthelmintically active ministered to the host animal in the presence of a tricyclic 2-substituted benzimidazole. The 2-substituted benzimida compound selected from the group consisting of dibenzo - Zoles contemplated for use in the present invention have cycloheptenes and thioxanthenes. -
9: Analytical Standards
CATALOGUE NUMBER 9 ANALYTICAL STANDARDS Table of Contents Standards for Special Applications 3 Standards for Routine Analytical Applications 82 Certified Primary Pharmaceutical Standards 3 Environmental Standards 82 Certified GMO Materials 31 Particle Size Standards 115 Certified Clinical Chemistry Standards 33 Conductivity Standards 116 Other Certified Standards 34 Ion Chromatography Standards 116 Custom & OEM Standards 44 Redox Standards 117 Certified Industrial Raw Materials 44 Forensic & Veterinary Standards 117 Certified Drugs, Metabolites, & Impurities 45 Polymer Standards 126 Certified Food & Agriculture Standards 58 Petrochemical Standards 127 Proficiency Testing for Environmental Analysis 60 AAS/ICP Standards 130 Chromatography & CE Test Mixes 131 Selected Certified Reference Materials 64 TOC Standards 132 Environmental Standards 64 Melting Point Standards 132 Trace Cert Organics 75 Spectroscopy Standards—TraceCert 132 Occupational Hygiene Standards 76 MS Markers 134 Secondary Pharma Standards 76 Pharmaceutical & Clinical Standards 134 Titrimetric Substances 81 X-Ray Standards 135 Certified Spectroscopy Standards 81 Food & Beverage Standards 135 Gravimetry Standards 147 NMR Standards 147 Color Reference Solutions 148 Miscellaneous 148 NOTE: This publication is designed for electronic use only. Hazard and Safety information can be found on product detail pages and at sigma-aldrich.com/safetycenter. 2 Analytical Standards Technical Support: [email protected] Standards for Special Applications Certified Primary Pharmaceutical -
(12) United States Patent (10) Patent No.: US 7,897,788 B2 Fecher Et Al
US007897788B2 (12) United States Patent (10) Patent No.: US 7,897,788 B2 Fecher et al. (45) Date of Patent: Mar. 1, 2011 (54) INDOL-1-YL-ACETIC ACID DERIVATIVES OTHER PUBLICATIONS Chemical Abstracts Registry No. 347911-97-1, entry date into the (75) Inventors: Anja Fecher, Basel (CH); Heinz Fretz, Registry file on STN is Jul 24, 2001.* Riehen (CH); Kurt Hilpert, Hofstetten Souillac, et al., Characterization of Delivery Systems, Differential (CH); Markus Riederer, Liestal (CH) Scanning Calorimetry in Encyclopedia of Controlled Drug Delivery, 1999, John Wiley & Sons, pp. 212-227.* (73) Assignee: Actelion Pharmaceutical Ltd., Vippagunta et al. (Advanced Drug Delivery Reviews, 48 (2001), pp. Allschwil (CH) 3-26. Doan et al., Journal of Clinical Pharmacology, 2005, 45, pp. 751 (*) Notice: Subject to any disclaimer, the term of this 762.* patent is extended or adjusted under 35 Barnes et al., European Respiratory Journal, 2005, 25, pp. 1084 U.S.C. 154(b) by 1196 days. 1105.* Philip L. Gould. International Journal of Pharmaceutics, vol. 33, pp. (21) Appl. No.: 10/598,781 201-217 (1986). Warawa et al., J. Med. Chem... vol. 44, pp. 372-389 (2001). (22) PCT Filed: Mar. 8, 2005 Gastpar et al., J. Med. Chem... vol. 41, pp. 4965-4972 (1998). Richard C. Larocket al., "Comprehensive Organic Transformations: (86). PCT No.: PCT/EP2OOS/OO2418 A Guide to Functional Group Preparations'. Wiley-VCH publishers, Second Edition (1999). S371 (c)(1), Berge et al., Journal of Pharmaceutical Sciences, vol. 66, pp. 1-19 (2), (4) Date: Sep. 11, 2006 (1977). Sawyer et al., British Journal of Pharmacology, vol. -
Protriptyline Hcl Tablets, USP
PROTRIPTYLINE HYDROCHLORIDE- protriptyline hydrochloride tablet, film coated Sigmapharm Laboratories, LLC ---------- Protriptyline HCl Tablets, USP Suicidality and Antidepressant Drugs Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of protriptyline hydrochloride or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Protriptyline hydrochloride is not approved for use in pediatric patients. (See Warnings: Clinical Worsening and Suicide Risk, PRECAUTIONS: Information for Patients, and Precautions: Pediatric Use) DESCRIPTION Protriptyline HCl is N-methyl-5H dibenzo [a,d]-cycloheptene-5-propanamine hydrochloride. Its molecular formula is C 19H 21N•HCl and its structural formula is: Protriptyline HCl, dibenzocycloheptene derivative, has a molecular weight of 299.84. It is a white to yellowish powder that is freely soluble in water and soluble in dilute HCl. Protriptyline HCl is supplied as 5 mg or 10 mg film-coated tablets.