DOCSLIB.ORG

(12) United States Patent (10) Patent No.: US 7,671,056 B2 Asselin Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) United States Patent (10) Patent No.: US 7,671,056 B2 Asselin Et Al USOO7671056 B2 (12) United States Patent (10) Patent No.: US 7,671,056 B2 Asselin et al. (45) Date of Patent: Mar. 2, 2010 (54) PIPERAZINE-PIPERIDINE ANTAGONISTS 6,995, 176 B2 2/2006 Bernotas et al. AND AGONISTS OF THE 5-HT, RECEPTOR 7,041,695 B2 5, 2006 Cole 2003/0060513 A1 3/2003 Arneric et al. 2003, O220348 A1 11/2003 Xie et al. (75) Inventors: Magda Asselin, Mahwah, NJ (US); 2004, OO14972 A1 1/2004 Gottschlich et al. George Theodore Grosu, Pearl River, 2005/0032873 A1 2/2005 Hatzenbuhler et al. NY (US); Annmarie Louise Sabb, 2005, 0182049 A1 8, 2005 Howard Pennington, NJ (US); Wayne Everett 2005/O197356 A1 9, 2005 Graziani et al. Childers, New Hope, PA (US); Lisa 2005/O197379 A1 9, 2005 Summers et al. Marie Havran, Florence, NJ (US); 2005/0215561 A1 9, 2005 Ghosh et al. Zhongqi Shen, Plainsboro, NJ (US); 2005/0256103 A1 11/2005 Suzuki et al. James Jacob Bicksler, Titusville, NJ 2005/0282825 A1 12/2005 Malamas et al. (US); Dan Chaekoo Chong, Plainsboro, 2005/0282826 A1 12/2005 Malamas et al. 2006, O1828.05 A1 8, 2006 Pfeiffer et al. NJ (US) 2006/0287335 A1 12/2006 Sukoffet al. 2007/0027160 A1 2/2007 Asselin et al. (73) Assignee: Wyeth LLC, Madison, NJ (US) 2007/O146072 A1 6/2007 Ohta et al. (*) Notice: Subject to any disclaimer, the term of this 2007,029.9083 A1 12/2007 Schmid et al. patent is extended or adjusted under 35 U.S.C. 154(b) by 280 days. (Continued) FOREIGN PATENT DOCUMENTS (21) Appl. No.: 11/450,942 EP 1203584 5, 2002 (22) Filed: Jun. 9, 2006 (Continued) (65) Prior Publication Data OTHER PUBLICATIONS US 2007/0027160 A1 Feb. 1, 2007 Araneda, et al., “5-Hydroxytryptamine and 5-Hydroxytryptamine Related U.S. Application Data Receptors Mediate Opposing Responses on Membrane Excitability in Rat Association Cortex'. Neuroscience, 40(2):399-412 (1991). (60) Provisional application No. 60/689,469, filed on Jun. 10, 2005. (Continued) Primary Examiner Emily Bernhardt (51) Int. Cl. (74) Attorney, Agent, or Firm Rebecca R. Barrett A6 IK 3/496 (2006.01) CO7D 40/4 (2006.01) (57) ABSTRACT CO7D 40.5/14 (2006.01) CO7D 409/14 (2006.01) The present invention relates to novel piperazine-piperidine CO7D 413/14 (2006.01) compounds. The compounds are useful as 5-HT1A binding (52) U.S. Cl. ............................ 514/253.06; 514/253.07; agents, particularly as 5-HT1A receptor antagonists and ago 514/253.08: 514/253.09: 514/253.1: 514/253.11; nists. These compounds are useful in treating central nervous 544/363; 544/360; 544/364 system disorders, such as cognition disorders, anxiety disor (58) Field of Classification Search ....................... None ders, depression and sexual dysfunction. The invention See application file for complete search history. relates to compounds and pharmaceutically acceptable salts (56) References Cited of formula (I): U.S. PATENT DOCUMENTS I 4,465,482 A 8, 1984 Tittel et al. 4,624,954. A 1 1/1986 Jirkovsky et al. 4,665,183 A 5/1987 Jirkovsky et al. 4,904,658 A 2/1990 Tsenget al. 5,219,857 A 6/1993 Tsenget al. R3 / \ N Ra R3 R14 5,260,331 A 11/1993 White et al. 5,288,748 A 2f1994 Wikstrom et al. 5,422,355 A 6, 1995 White et al. N N 5,538,956 A 7, 1996 Minchin et al. 6,084,130 A 7/2000 Romero et al. \ { pi 6,127,357 A 10, 2000 Cliffe et al. Rs R6 Rb Rs R16 R7 R8 6,465,482 B2 10/2002 Mewshaw et al. 6,469,007 B2 10/2002 Childers et al. wherein R.-R. R. R. and n are set forth in the specifica 6,586,436 B2 7/2003 Childers et al. tion. The invention also relates to pharmaceutical composi 6,620,808 B2 9, 2003 Van Der Klish et al. 6,635,270 B2 10/2003 Hong et al. tions comprising compounds and pharmaceutically accept 6,821,985 B2 11/2004 Chenard et al. able salts of formula (I'). 6.825,212 B2 11/2004 Bernotas et al. 6,878,742 B2 4/2005 Kreft et al. 67 Claims, No Drawings US 7,671,056 B2 Page 2 U.S. PATENT DOCUMENTS Carli, et al., “(S)-WAY 100135, a 5-HT Receptor Antagonist, Prevents the Impairment of Spatial Learning Caused by Intrahip 2008, OO4551.0 A1 2/2008 Liang et al. pocampal Scopolamine'. European Journal of Pharmacology, 2008.00.58523 A1 3/2008 Liu et al. 283:133-139 (1995). Childers, et al., “Synthesis and Biological Evaluation of FOREIGN PATENT DOCUMENTS Benzodioxanylpiperazine Derivatives as Potent Serotonin 5-HT EP 1541197 6, 2005 Antagonists: The Discovery of Lecozotan', J.Med. Chem., 48:3467 WO WO-94/O2475 2, 1994 3470 (2005). WO WO-94.13643 6, 1994 Dijk, et al., “NMDA-Induced Glutamate and Aspartate Release from WO WO-94.13644 6, 1994 Rat Cortical Pyramidal Neurones: Evidence for Modulation By a WO WO-94.13661 6, 1994 5-HT, Antagonist”. British Journal of Pharmacology, 115: 1169 WO WO-94/13676 6, 1994 1174 (1995). WO WO-94/13677 6, 1994 Dimitriou, "Buspirone Augmentation of Antidepressant Therapy'. J. WO WO-95/33743 12/1995 Clinical Psychopharmacol., 18(6):465-469 (1998). WO WO-96,38414 12/1996 Driver, et al., “A Second-Generation Catalyst for Aryl Halide Amina WO WO-97/03982 2, 1997 tion: Mixed Secondary Amines from Aryl Halides and Primary WO WO-97,36907 10, 1997 Amines Catalyzed by (DPPF)PdCI”. J. Am. Chem. Soc., 118:7217 WO WO-98, 15275 4f1998 7218 (1996). WO WO-99/42456 8, 1999 Dunlop, et al., “Characterization of 5-HT Receptor Functional WO WO-99,51240 10, 1999 Coupling in Cells Expressing the Human 5-HT Receptor as WO WO-OO,321.87 6, 2000 Assesed with the Cytosensor Microphysiometer'. Journal of Phar WO WO-OOf 40554 T 2000 macological and Toxicological Methods, 40:47-55 (1998). WO WO-O 1/77 100 10, 2001 Feiger, "A Double-Blind Comparison of Gepirone Extended Release, WO WO-O2,20491 3, 2002 Imipramine, and Placebo in the Treatment of Outpatient Major WO WO-02/088132 11, 2002 Depression”, Psychopharmacol. Bull., 32(4):659-665 (1996). WO WO-02/0881.45 11, 2002 Grof. et al., “An Open Study of Oral Flesinoxan, a 5-HT Receptor WO WO-03/010169 2, 2003 Agonist, in Treatment-Resistant Depression'. International Clinical WO WOO3,087.086 10, 2003 Psychopharmacology, 8: 167-172 (1993). WO WO-2004/016256 2, 2004 Harder, et al., “The 5-HT Antagonist, WAY 100 635, Alleviates WO WO-2004/O24731 3, 2004 Cognitive Impairments Induced by Dizocilpine (MK-801) in Mon WO WO-2004/045509 6, 2004 keys'. Neuropharmacology, 39:547-552 (2000). WO WO-2004/045718 6, 2004 Harder, et al., “The 5-HT, Antagonist, WAY 100635, Ameliorates WO WO-2004/099.191 11, 2004 the Cognitive Impairment Induced by Fornix Transection in the Mar WO WO-2004/099214 11, 2004 moset', Psychopharmacology, 127:245-254 (1996). WO WO-2005/056560 6, 2005 Hume, et al., “Evaluation of O-methyl-HIWAY-100635 as an in WO WO-2006/042249 4/2006 vivo Radioligand for 5-HT Receptors in Rat Brain'. European WO WO-2006,1358.39 12/2006 Journal of Pharmacology, 271:515-523 (1994). WO WO-2007/146072 12/2007 Jones. “Synthesis of the Quinoline Ring System”. Heterocyclic Com WO WO-2007/146073 12/2007 pounds: Vol. 32 (Quinolines), Chapter 2, InterScience, New York, pp. 93-318 (1977). WO WO-2007 146115 12/2007 Matsuyama, et al., “Regulation of Glutamate Release via NMDA and WO WO-2007 1462O2 12/2007 5-HT Receptors in Guinea Pig Dentate Gyrus'. Brain Research, WO WO-2008/067399 6, 2008 728:175-180 (1996). Mcloughlin, et al., “Central Serotonergic Hyperresponsivity in Late OTHER PUBLICATIONS Onset Alzheimer's Disease'. American Journal of Psychiatry, 151(11): 1701-1703 (1994). Artigas, et al., "Acceleration of the Effect of Selected Antidepressant Perez, et al., “Randomised, Double-Blind, Placebo-Controlled Trial Drugs in Major Depression by 5-HT1. Antagonists'. Trends in Pindolol in Combination with Fluoxetine Antidepressant Treat Neurosci., 19(9):378-383 (1996). ment”. The Lancet, 349:1594-1597 (1997). Balducci, et al., “Reversal of Visual Attention Dysfunction after Rabiner, et al., “5-Hydroxytryptamine Receptor Occupancy by AMPA Lesions of the Nucleus Basalis Maqnocellularis (NBM) by Novel Full Antagonist 2-4-4-(7-Chloro-2,3-dihydro-1,4- the Cholinesterase Inhibitor Donepezil and by a 5-HT Receptor benzdioxyn-5-yl)-1-piperazinylbutyl-1,2-benzisothiazol-3-(2H)- Antagonist WAY 100635”. Psychopharmacology, 167:28-36 (2003). one-1,1-dioxide: A CIO-methyl-3H-N-(2-(4-(2- Blier, et al., “Effectiveness of Pindolol with Selected Antidepressant methoxyphenyl)-1-piperazinyl)ethyl)-N-(2- Drugs in the Treatment of Major Depression”. J. Clin. pyridinyl)cyclohexanecarboxamide Trihydrochloride (WAY Psychopharmacol., 15(3):217-222 (1995). 100635) Positron Emission Tomography Study in Humans”,Journal Blier, et al., “Modifications of the Serotonin System by Antidepres of Pharmacology and Experimental Therapeutics, 301(3): 1144-1150 Sant Treatments: Implications for the Therapeutic Response in Major (2002). Depression”, Journal of Clinical Psychopharmacology, 7(6 Sakai, et al., “Inhibitory Modulation of Long-Term Potentiation via Suppl):24S-35S (1987). the 5-HT Receptor in Slices of the Rat Hippocampal Dentate Boast, et al., “5HT Antagonists Attenuate MK801-Impaired Radial Gyrus', Brain Research, 613:326-330 (1993). Arm Maze Performance in Rats'. Neurobiology of Learning and Schechter, et al., “Lecozotan (SRA-333): A Selective Serotonin 1A Memory, 71:259-271 (1999).
Load more

Recommended publications
  • Alzheimer's Disease Clinical Trials
    Clinical Trial Perspective 5 Clinical Trial Perspective Alzheimer’s disease clinical trials: past failures and future opportunities Clin. Invest. (Lond.) Over a decade has elapsed since the US FDA has approved a medication for Alzheimer’s Roy Yaari*,1,2 & Ann Hake1,2 disease (AD) despite clinical trials of numerous agents over a wide array of mechanisms 1Eli Lilly & Company, Lilly Corporate including neurotransmitter modulation and disease modifying therapy targeting Center, Indianapolis, IN 46285, USA 2Indiana University School of Medicine, amyloid and tau. The failures of clinical trials in AD may be due to inadequate Department of Neurology, Indianapolis, understanding of mechanisms of action and/or poor target engagement; however, IN 46202, USA other factors could include inadequate study design, stage of AD along the continuum *Author for correspondence: studied, inclusion of participants without Alzheimer’s pathology into clinical trials Tel.: +1 317 651 6163 and limited power of endpoint measures. Future studies will need to carefully assess [email protected] these possible shortcomings in design of upcoming trials, especially as the field moves toward studies of disease modifying agents (as opposed to symptomatic treatment) of AD and to patients that are very early in the disease spectrum. Keywords: Alzheimer’s disease • Alzheimer’s disease biomarkers • amyloid • clinical trials • preclinical Alzheimer’s disease • tau US FDA approved medications continue to provide significant, but modest More than three decades ago, the choliner- symptomatic benefit[5–7] . gic hypothesis proposed that degeneration The compound memantine introduced a of cholinergic neurons in the basal fore- second mechanism for symptomatic treat- brain and the associated loss of cholinergic ment of AD into clinical practice.
    [Show full text]
  • TESE FINAL.Pdf
    FACULDADE DE MEDICINA DA UNIVERSIDADE DE COIMBRA TRABALHO FINAL DO 6º ANO MEDICO COM VISTA A ATRIBUIÇÃO DO GRAU DE MESTRE NO ÂMBITO DO CICLO DE ESTUDOS DO MESTRADO INTEGRADO EM MEDICINA ANA ALEXANDRA BRIGA CERQUEIRA ESTRATÉGIAS FARMACOLÓGICAS PARA AS ALTERAÇÕES PRECOCES DO COMPORTAMENTO NA DOENÇA DE ALZHEIMER TRABALHO DE REVISÃO ÁREA CIENTÍFICA DE FARMACOLOGIA TRABALHO REALIZADO SOBRE A ORIENTAÇÃO DE: PROFESSORA DOUTORA TICE DOS REIS ANASTÁCIO DE MACEDO MARÇO, 2009 ÍNDICE GERAL Agradecimentos.................................................................................................................3 Resumo..............................................................................................................................4 Abstract..............................................................................................................................6 Lista de Siglas....................................................................................................................8 Introdução........................................................................................................................11 Clínica e Diagnóstico……………...……………………………………………………11 Neuropatologia e Genética..............................................................................................15 Estratégias terapêuticas actuais...................................…………………………………23 Inibidores das colinesterases……………………………………………………23 Memantina……………………………………………………………………...27 Novas estratégias farmacológicas………………………………………………………30 Imunoterapia……………………………………………………………………34
    [Show full text]
  • (12) United States Patent (10) Patent N0.: US 7,964,607 B2 Verhoest Et A1
    US007964607B2 (12) United States Patent (10) Patent N0.: US 7,964,607 B2 Verhoest et a1. (45) Date of Patent: Jun. 21, 2011 (54) PYRAZOLO[3,4-D]PYRIMIDINE FOREIGN PATENT DOCUMENTS COMPOUNDS EP 1460077 9/2004 WO 02085904 10/2002 (75) Inventors: Patrick Robert Verhoest, Old Lyme, CT WO 2004037176 5/2004 (US); Caroline ProulX-Lafrance, Ledyard, CT (US) OTHER PUBLICATIONS Wunder et a1, M01. PharmacoL, v01. 28, N0. 6, (2005), pp. 1776 (73) Assignee: P?zer Inc., New York, NY (U S) 1781. van der Staay et a1, Neuropharmacology, v01. 55 (2008), pp. 908 ( * ) Notice: Subject to any disclaimer, the term of this 918. patent is extended or adjusted under 35 USC 154(b) by 562 days. Primary Examiner * Susanna Moore (74) Attorney, Agent, or Firm * Jennifer A. Kispert; (21) Appl.No.: 12/118,062 Michael Herman (22) Filed: May 9, 2008 (57) ABSTRACT (65) Prior Publication Data The invention provides PDE9-inhibiting compounds of For US 2009/0030003 A1 Jan. 29, 2009 mula (I), Related US. Application Data (60) Provisional application No. 60/917,333, ?led on May 11, 2007. (51) Int. Cl. C07D 48 7/04 (2006.01) A61K 31/519 (2006.01) A61P 25/28 (2006.01) (52) US. Cl. ................................... .. 514/262.1; 544/262 (58) Field of Classi?cation Search ................ .. 544/262; 5 1 4/2 62 .1 See application ?le for complete search history. and pharmaceutically acceptable salts thereof, Wherein R, R1, (56) References Cited R2 and R3 are as de?ned herein. Pharmaceutical compositions containing the compounds of Formula I, and uses thereof in U.S.
    [Show full text]
  • Pharmaceutical Appendix to the Tariff Schedule 2
    Harmonized Tariff Schedule of the United States (2007) (Rev. 2) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2007) (Rev. 2) Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. ABACAVIR 136470-78-5 ACIDUM LIDADRONICUM 63132-38-7 ABAFUNGIN 129639-79-8 ACIDUM SALCAPROZICUM 183990-46-7 ABAMECTIN 65195-55-3 ACIDUM SALCLOBUZICUM 387825-03-8 ABANOQUIL 90402-40-7 ACIFRAN 72420-38-3 ABAPERIDONUM 183849-43-6 ACIPIMOX 51037-30-0 ABARELIX 183552-38-7 ACITAZANOLAST 114607-46-4 ABATACEPTUM 332348-12-6 ACITEMATE 101197-99-3 ABCIXIMAB 143653-53-6 ACITRETIN 55079-83-9 ABECARNIL 111841-85-1 ACIVICIN 42228-92-2 ABETIMUSUM 167362-48-3 ACLANTATE 39633-62-0 ABIRATERONE 154229-19-3 ACLARUBICIN 57576-44-0 ABITESARTAN 137882-98-5 ACLATONIUM NAPADISILATE 55077-30-0 ABLUKAST 96566-25-5 ACODAZOLE 79152-85-5 ABRINEURINUM 178535-93-8 ACOLBIFENUM 182167-02-8 ABUNIDAZOLE 91017-58-2 ACONIAZIDE 13410-86-1 ACADESINE 2627-69-2 ACOTIAMIDUM 185106-16-5 ACAMPROSATE 77337-76-9
    [Show full text]
  • Revisiting the Pharmacodynamics Uroselectivity of Alpha1-Adrenergic
    JPET Fast Forward. Published on July 8, 2019 as DOI: 10.1124/jpet.119.260216 This article has not been copyedited and formatted. The final version may differ from this version. JPET # 260216 TITLE PAGE Revisiting the pharmacodynamics uroselectivity of Alpha1-Adrenergic Receptor Antagonists Downloaded from Authors: Bruna Maria Castro Salomão Quaresma, Amanda Reis Pimenta, Anne Caroline jpet.aspetjournals.org Santos da Silva, André Sampaio Pupo, Luiz Antonio S. Romeiro, Claudia Lucia Martins Silva and François Noël* *Corresponding author at ASPET Journals on September 29, 2021 1 JPET Fast Forward. Published on July 8, 2019 as DOI: 10.1124/jpet.119.260216 This article has not been copyedited and formatted. The final version may differ from this version. JPET # 260216 RUNNING TITLE PAGE Running Title: Uroselectivity of alpha1-adrenergic antagonists Corresponding author: François Noël Laboratory of Biochemical and Molecular Pharmacology, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Av Carlos Chagas Filho, 373. Zip code 21941-902, Rio de Janeiro, Brazil. Downloaded from Phone number: +55 (21) 3938-6732 e-mail: [email protected] jpet.aspetjournals.org Av Carlos Chagas Filho, 373. Zip code 21941-902, Rio de Janeiro, Brazil. Number of text pages: 28 (including legends for figures) at ASPET Journals on September 29, 2021 Number of tables: 4 Number of figures: 2 (+ 1 in Supplemental material) Number of references: 48 Number of words: Abstract: 238 Introduction: 667 Discussion: 1233 Non-standard abbreviations: AARA, α1-AR antagonists; AR, α1-adrenoceptor; BPH, benign prostatic hyperplasia; DMEM, Dulbecco’s Modified Eagle Medium; DMSO, dimethyl 2 JPET Fast Forward.
    [Show full text]
  • BDNF Pathway in Rat Model of Depression Through Chronic Unpredictable Stress Chunye Wang1, Jianyou Guo2* and Rongjuan Guo1*
    Wang et al. BMC Complementary and Alternative Medicine (2017) 17:73 DOI 10.1186/s12906-016-1543-9 RESEARCH ARTICLE Open Access Effect of XingPiJieYu decoction on spatial learning and memory and cAMP-PKA-CREB- BDNF pathway in rat model of depression through chronic unpredictable stress Chunye Wang1, Jianyou Guo2* and Rongjuan Guo1* Abstract Background: Depression is a mental disorder characterized by a pervasive low mood and loss of pleasure or interest in usual activities, and often results in cognitive dysfunction. The disturbance of cognitive processes associated with depression, especially the impairment of learning and memory, exacerbates illness and increases recurrence of depression. XingPiJieYu (XPJY) is one of the most widely clinical formulas of traditional Chinese medicine (TCM) and can improve the symptoms of depression, including learning and memory. However, its regulatory effects haven’t been comprehensively studied so far. Recently, some animal tests have indicated that the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element-binding protein (CREB)- brain derived neurotrophic factor (BDNF) signaling pathway in hippocampus is closely related to depression and the pathogenesis of cognitive function impairments. The present study was performed to investigate the effect and mechanism of XPJY on depression and learning and memory in animal model. Materials: The rat model of depression was established by chronic unpredictable stress (CUS) for 21 days. The rats were randomly divided into six groups: control group, CUS group, CUS + XPJY (1.4 g/kg, 0.7 g/kg and 0.35 g/kg) groups, and CUS + sertraline (10 mg/kg) group. The sucrose preference, open field exploration and Morris water maze (MWM) were tested.
    [Show full text]
  • Stembook 2018.Pdf
    The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
    [Show full text]
  • A Abacavir Abacavirum Abakaviiri Abagovomab Abagovomabum
    A abacavir abacavirum abakaviiri abagovomab abagovomabum abagovomabi abamectin abamectinum abamektiini abametapir abametapirum abametapiiri abanoquil abanoquilum abanokiili abaperidone abaperidonum abaperidoni abarelix abarelixum abareliksi abatacept abataceptum abatasepti abciximab abciximabum absiksimabi abecarnil abecarnilum abekarniili abediterol abediterolum abediteroli abetimus abetimusum abetimuusi abexinostat abexinostatum abeksinostaatti abicipar pegol abiciparum pegolum abisipaaripegoli abiraterone abirateronum abirateroni abitesartan abitesartanum abitesartaani ablukast ablukastum ablukasti abrilumab abrilumabum abrilumabi abrineurin abrineurinum abrineuriini abunidazol abunidazolum abunidatsoli acadesine acadesinum akadesiini acamprosate acamprosatum akamprosaatti acarbose acarbosum akarboosi acebrochol acebrocholum asebrokoli aceburic acid acidum aceburicum asebuurihappo acebutolol acebutololum asebutololi acecainide acecainidum asekainidi acecarbromal acecarbromalum asekarbromaali aceclidine aceclidinum aseklidiini aceclofenac aceclofenacum aseklofenaakki acedapsone acedapsonum asedapsoni acediasulfone sodium acediasulfonum natricum asediasulfoninatrium acefluranol acefluranolum asefluranoli acefurtiamine acefurtiaminum asefurtiamiini acefylline clofibrol acefyllinum clofibrolum asefylliiniklofibroli acefylline piperazine acefyllinum piperazinum asefylliinipiperatsiini aceglatone aceglatonum aseglatoni aceglutamide aceglutamidum aseglutamidi acemannan acemannanum asemannaani acemetacin acemetacinum asemetasiini aceneuramic
    [Show full text]
  • WO 2015/049616 Al 9 April 2015 (09.04.2015) P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2015/049616 Al 9 April 2015 (09.04.2015) P O P C T (51) International Patent Classification: (74) Agent: OLSON, A. Dean; Pfizer Inc., c/o Eastern Point C07D 471/04 (2006.01) A61K 31/498 (2006.01) Road, Groton, Connecticut 06340 (US). C07D 498/04 (2006.01) A61P 25/00 (2006.01) (81) Designated States (unless otherwise indicated, for every (21) International Application Number: kind of national protection available): AE, AG, AL, AM, PCT/IB2014/064738 AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (22) Date: International Filing DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, 22 September 2014 (22.09.2014) HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (25) Filing Language: English KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (26) Publication Language: English PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, (30) Priority Data: SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, 61/886,705 4 October 201 3 (04. 10.2013) US TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (71) Applicant: PFIZER INC. [US/US]; 235 East 42nd Street, (84) Designated States (unless otherwise indicated, for every New York, New York 10017 (US).
    [Show full text]
  • Therapeutics of Alzheimer's Disease: Past, Present and Future
    Neuropharmacology 76 (2014) 27e50 Contents lists available at ScienceDirect Neuropharmacology journal homepage: www.elsevier.com/locate/neuropharm Review Therapeutics of Alzheimer’s disease: Past, present and future R. Anand a,*, Kiran Dip Gill b, Abbas Ali Mahdi c a Department of Biochemistry, Christian Medical College, Vellore 632002, Tamilnadu, India b Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India c Department of Biochemistry, King George’s Medical University, Lucknow, UP, India article info abstract Article history: Alzheimer’s disease (AD) is the most common cause of dementia worldwide. The etiology is multifac- Received 29 December 2012 torial, and pathophysiology of the disease is complex. Data indicate an exponential rise in the number of Received in revised form cases of AD, emphasizing the need for developing an effective treatment. AD also imposes tremendous 26 June 2013 emotional and financial burden to the patient’s family and community. The disease has been studied over Accepted 2 July 2013 a century, but acetylcholinesterase inhibitors and memantine are the only drugs currently approved for its management. These drugs provide symptomatic improvement alone but do less to modify the disease Keywords: process. The extensive insight into the molecular and cellular pathomechanism in AD over the past few Alzheimer’s disease fi Amyloid decades has provided us signi cant progress in the understanding of the disease. A number of novel Dementia strategies that seek to modify the disease process have been developed. The major developments in this Neuropharmacology direction are the amyloid and tau based therapeutics, which could hold the key to treatment of AD in the Neurofibrillary tangles near future.
    [Show full text]
  • WO 2015/150957 Al 8 October 2015 (08.10.2015) P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2015/150957 Al 8 October 2015 (08.10.2015) P O P C T (51) International Patent Classification: (74) Agent: OLSON, A. Dean; Pfizer Worldwide Research & C07D 471/04 (2006.01) A61P 25/28 (2006.01) Development, Eastern Point Road MS8260-2141, Groton, A61K 31/4985 (2006.01) Connecticut 06340 (US). (21) International Application Number: (81) Designated States (unless otherwise indicated, for every PCT/IB20 15/05 1988 kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (22) International Filing Date: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, 18 March 2015 (18.03.2015) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (25) Filing Language: English HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, (26) Publication Language: English MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (30) Priority Data: PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, 61/973,436 1 April 2014 (01.04.2014) US SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (71) Applicant: PFIZER INC. [US/US]; 235 East 42nd Street, New York, New York 10017 (US).
    [Show full text]
  • Florencio Zaragoza Dörwald Lead Optimization for Medicinal Chemists
    Florencio Zaragoza Dorwald¨ Lead Optimization for Medicinal Chemists Related Titles Smith, D. A., Allerton, C., Kalgutkar, A. S., Curry, S. H., Whelpton, R. van de Waterbeemd, H., Walker, D. K. Drug Disposition and Pharmacokinetics and Metabolism Pharmacokinetics in Drug Design From Principles to Applications 2012 2011 ISBN: 978-3-527-32954-0 ISBN: 978-0-470-68446-7 Gad, S. C. (ed.) Rankovic, Z., Morphy, R. Development of Therapeutic Lead Generation Approaches Agents Handbook in Drug Discovery 2012 2010 ISBN: 978-0-471-21385-7 ISBN: 978-0-470-25761-6 Tsaioun, K., Kates, S. A. (eds.) Han, C., Davis, C. B., Wang, B. (eds.) ADMET for Medicinal Chemists Evaluation of Drug Candidates A Practical Guide for Preclinical Development 2011 Pharmacokinetics, Metabolism, ISBN: 978-0-470-48407-4 Pharmaceutics, and Toxicology 2010 ISBN: 978-0-470-04491-9 Sotriffer, C. (ed.) Virtual Screening Principles, Challenges, and Practical Faller, B., Urban, L. (eds.) Guidelines Hit and Lead Profiling 2011 Identification and Optimization ISBN: 978-3-527-32636-5 of Drug-like Molecules 2009 ISBN: 978-3-527-32331-9 Florencio Zaragoza Dorwald¨ Lead Optimization for Medicinal Chemists Pharmacokinetic Properties of Functional Groups and Organic Compounds The Author All books published by Wiley-VCH are carefully produced. Nevertheless, authors, Dr. Florencio Zaragoza D¨orwald editors, and publisher do not warrant the Lonza AG information contained in these books, Rottenstrasse 6 including this book, to be free of errors. 3930 Visp Readers are advised to keep in mind that Switzerland statements, data, illustrations, procedural details or other items may inadvertently be Cover illustration: inaccurate.
    [Show full text]