DOCSLIB.ORG

Piperidine Derivatives Useful As Ccr5

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Piperidine Derivatives Useful As Ccr5 Europäisches Patentamt & (19) European Patent Office Office européen des brevets (11) EP 1 421 075 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: C07D 401/04 (2006.01) A61P 31/18 (2006.01) 07.06.2006 Bulletin 2006/23 A61K 31/435 (2006.01) (21) Application number: 02766142.0 (86) International application number: PCT/US2002/027389 (22) Date of filing: 28.08.2002 (87) International publication number: WO 2003/020716 (13.03.2003 Gazette 2003/11) (54) PIPERIDINE DERIVATIVES USEFUL AS CCR5 ANTAGONISTS FOR THE TREATMENT OF HIV PIPERIDIN DERIVATE ALS CCR5 REZEPTOR ANTAGONISTEN ZUR BEHANDLUNG VON HIV DERIVES DE LA PIPERIDINE UTILISES COMME ANTAGONISTES DU CCR5 POUR LE TRAITEMENT DU SIDA (84) Designated Contracting States: (74) Representative: Adams, Harvey Vaughan John et AT BE BG CH CY CZ DE DK EE ES FI FR GB GR al IE IT LI LU MC NL PT SE SK TR Mathys & Squire Designated Extension States: 120 Holborn AL LT LV MK RO SI London EC1N 2SQ (GB) (30) Priority: 29.08.2001 US 315683 P (56) References cited: EP-A- 0 151 824 EP-A- 0 855 999 (43) Date of publication of application: WO-A-01/30348 WO-A-01/77101 26.05.2004 Bulletin 2004/22 WO-A-97/24324 WO-A-98/01425 WO-A-02/081449 US-A- 5 952 349 (73) Proprietor: SCHERING CORPORATION Kenilworth, NJ 07033-0530 (US) • PALANI, A. ET AL.: "Discovery of 4-[(Z)-(4- Bromophenyl)-(ethoxyimino)methyl ]-1’-[(2,4- (72) Inventors: dimethyl-3-pyridinyl)carbonyl]- 4’-methyl-1,4’- • PALANI, Anandan bipiperidine N-Oxide (SCH 351125): An Orally Bridgewater, NJ 08807 (US) Bioavailable Human CCR5 Antagonist for the • MILLER, Michael, W. Treatment of HIV Infection" JOURNAL OF Westfield, NJ 07090 (US) MEDICINAL CHEMISTRY, vol. 44, no. 21, 11 • SCOTT, Jack, D. October 2001 (2001-10-11), pages 3339-3342, Springfield, NJ 07081 (US) XP002220286 Note: Within nine months from the publication of the mention of the grant of the European patent, any person may give notice to the European Patent Office of opposition to the European patent granted. Notice of opposition shall be filed in a written reasoned statement. It shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). EP 1 421 075 B1 Printed by Jouve, 75001 PARIS (FR) EP 1 421 075 B1 Description CROSS REFERENCE TO RELATED APPLICATION 5 [0001] This application claims priority to U.S. Provisional Application 60/315683, filed August 29, 2001. FIELD OF INVENTION [0002] The present invention relates to piperidine derivatives useful as selective CCR5 antagonists, pharmaceutical 10 compositions containing the compound of this invention, and methods of treatment using the inventive compounds. The invention also relates to the use of a combination of the compound of this invention and one or more antiviral or other agents useful in the treatment of Human Immunodeficiency Virus (HIV). The invention further relates to the use of the compound of this invention, alone or in combination with another agent, in the treatment of solid organ transplant rejection, graft v. host disease, arthritis, rheumatoid arthritis, inflammatory bowel disease, atopic dermatitis, psoriasis, asthma, 15 allergies or multiple sclerosis. BACKGROUND OF INVENTION [0003] The global health crisis caused by HIV, the causative agent of Acquired Immunodeficiency Syndrome (AIDS), 20 is unquestioned. While recent advances in drug therapies have been successful in slowing the progression of AIDS, there is still a need to find a safer, more efficient, less expensive way to control the virus. [0004] It has been reported that the CCR5 gene plays a role in resistance to HIV infection. HIV infection begins by attachment of the virus to a target cell membrane through interaction with the cellular receptor CD4 and a secondary chemokine co-receptor molecule, and proceeds by replication and dissemination of infected cells through the blood and 25 other tissue. There are various chemokine receptors, but for macrophage-tropic HIV, believed to be the key pathogenic strain that replicates in vivo in the early stages of infection, the principal chemokine receptor required for the entry of HIV into the cell is CCR5. Therefore, interfering with the interaction between the viral receptor CCR5 and HIV can block HIV entry into the cell. The present invention relates to small molecules which are CCR5 antagonists. [0005] CCR5 receptors have been reported to mediate cell transfer in inflammatory diseases such as arthritis, rheu- 30 matoid arthritis, atopic dermatitis, psoriasis, asthma and allergies. Inhibitors of such receptors are expected to be useful in the treatment of such diseases, and in the treatment of other inflammatory diseases or conditions such as inflammatory bowel disease, multiple sclerosis, solid organ transplant rejection and graft v. host disease. [0006] Other piperidine derivatives, which are muscarinic antagonists useful in the treatment of cognitive disorders such as Alzheimer’s disease, are disclosed in US patents 5,883,096, 6,037,352, 5,889,006, 5,952,349, and 5,977,138. 35 [0007] A-M. Vandamme et al., Antiviral Chemistry & Chemotherapy, 9:187-203 (1998) disclose current clinical treat- ments of HIV-1 infections in man including at least triple drug combinations or so-called Highly Active Antiretroviral Therapy ("HAART"). HAART involves various combinations of nucleoside reverse transcriptase inhibitors ("NRTI"), non- nucleoside reverse transcriptase inhibitors ("NNRTI") and HIV protease inhibitors ("PI"). In compliant drug- naive patients, HAART is effective in reducing mortality and the progression of HIV-1 to AIDS. However, these multidrug therapies do 40 not eliminate HIV-1 and long-term treatment usually results in multidrug resistance. Development of new drug therapies to provide better HIV-1 treatment remains a priority. SUMMARY OF THE INVENTION 45 [0008] The present invention provides a novel class of compounds as antagonists of the CCR5 receptor, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, and uses in the treatment, prevention or amelioration of one or more diseases associated with the CCR5 receptor. [0009] One aspect of the invention relates to a compound having the general structure shown in Formula 1: 50 55 2 EP 1 421 075 B1 5 10 or a pharmaceutically acceptable salt or solvate thereof; wherein: 15 R1 is 20 25 30 R2 is selected from the group consisting of H, alkyl, aryl, arylalkyl, heteroarylalkyl, alkylketone, arylketone, alkyl, haloalkyl, cycloalkyl, cycloheteroalkyl, cycloalkylalkyl, alkylsulfonyl, arylsulfonyl, alkoxyalkyl, or amide; 35 R3 is selected from the group consisting of aryl, 6- membered heteroaryl, fluorenyl; and diphenylmethyl, 6 membered heteroaryl-N-oxide, 40 45 wherein said aryl, fluorenyl, diphenyl or heteroaryl is optionally substituted with 1-4 substituents which can be the same or different and are independently selected from the group consisting of R11, R12. R13, R14 and R15; R4 is 1-3 substituents selected from the group consisting of H, halo, alkyl, haloalkyl, alkoxy, cycloalkyl, cycloheter- 7 oalkyl, amide, CF3, OCF3, aryl, heteroaryl, -XR , -C(O)C3-C8cycloalkyl, -C(O)C3-C8cycloheteroalkyl, -(C1-C6)alkyl- 21 22 20 21 22 8 8 N(R )SO2R , -(C1-C6)alkyl-C(O)NR R , -CN, -CO2H, -CO2R , R -aryl(C1-C6)alkyl-, R -heteroaryl(C1-C6) 50 8 21 22 21 22 alkyl-, -C(O)-(C1-C6)alkyl, R -aryl-C(O)-, -C(O)NR R , -C(O)NH2, -C(O)N(H)OH, -(C1-C6)alkyl-N(R )C(O)R , 21 22 -(C1-C6)alkyl-N(R )CO2R , 21 21 22 21 22 21 22 -(C1-C6)alkyl-N(R )C(O)NR R , -(C1-C6)alkyl-NR R , -(C1-C6)alkyl-NH2, (C1-C6)alkyl, -SO2NR R and 21 22 4 -SO2NR R , wherein R can be the same or different and is independently selected when there is more than one R4 present; 55 5 8 8 R is selected from the group consisting of H, arylalkyl, (C1-C6)alkyl, R -aryl(C1-C6)alkyl-, R -heteroaryl(C1-C6) 8 alkyl-, -SO2-(C1-C6)alkyl, -SO2-(C3-C6)cycloalkyl, -SO2-aryl, R -aryl-SO2-, -C(O)-(C1-C6)alkyl, -C(O)-(C4-C6)cy- 8 21 22 21 22 cloalkyl, R -aryl-C(O)-, -C(O)NR R , and -SO2NR R ; 6 R is H, -(C1-C6)alkyl, or -(C1-C6)haloalkyl; 3 EP 1 421 075 B1 R7 is selected from the group consisting of aryl, substituted aryl, heteroaryl, alkyl, haloalkyl and cycloalkyl; 8 R is 1, 2 or 3 substituents selected from the group consisting of H, halo, (C 1-C6)alkyl, (C1-C6)alkoxy, -CF3, -OCF3, 8 CH3C(O)-, -CN, CH 3SO2-, CF 3SO2- and -NH 2, wherein R can be the same or different and is independently selected when there are more than one R8 present; 5 R9, R10 and B can be the same or different and are each independently selected from the group consisting of hydrogen, (C1-C6)alkyl, and -(C1-C6)haloalkyl: 11 12 R and R can be the same or different and are each independently selected from the group consisting of (C 1-C6) 19 20 alkyl, -(C1-C6)haloalkyl, halogen, -NR R , -OH, CF3, -OCH3, -O-acyl, and -OCF3; 13 11 R is selected from the group consisting of hydrogen, R , H, phenyl, -NO 2, -CN, -CH 2F, -CHF 2, -CHO, -CH=NOR 19, 10 pyridyl-N-oxide, pyrimidinyl, pyrazinyl, N (R20)CONR20R21, -NHCONH(chloro-(C 1-C6)alkyl), -NHCONH((C 3-C10)-cy- cloalkyl(C1-C6)alkyl), -NHCO(C1-C6)alkyl, -NHCOCF3, -NHCOCF3, -NHSO2N((C1-C6)alkyl)2, -NHSO2(C1-C6)alkyl, 22 22 22 -N(SO2CF3)2, -NHCO2(C1-C6)alkyl, (C3-C10)cycloalkyl, -SR , -SOR , -SO2R , -SO2NH(C1-C6 alkyl), -OSO2 19 20 (C1-C6)alkyl, -OSO2CF3, hydroxy(C1-C6)alkyl, -CONR R , -CON(CH2CH2-O-CH3)2, -OCONH(C1-C6)alkyl, -CO2R19, -Si(CH3)3 and -B(OC(CH3)2)2; 15 14 15 R is selected from the group consisting of (C1-C6)alkyl, -(C1-C6)haloalkyl -NH2
Load more

Recommended publications
  • Classification Decisions Taken by the Harmonized System Committee from the 47Th to 60Th Sessions (2011
    CLASSIFICATION DECISIONS TAKEN BY THE HARMONIZED SYSTEM COMMITTEE FROM THE 47TH TO 60TH SESSIONS (2011 - 2018) WORLD CUSTOMS ORGANIZATION Rue du Marché 30 B-1210 Brussels Belgium November 2011 Copyright © 2011 World Customs Organization. All rights reserved. Requests and inquiries concerning translation, reproduction and adaptation rights should be addressed to [email protected]. D/2011/0448/25 The following list contains the classification decisions (other than those subject to a reservation) taken by the Harmonized System Committee ( 47th Session – March 2011) on specific products, together with their related Harmonized System code numbers and, in certain cases, the classification rationale. Advice Parties seeking to import or export merchandise covered by a decision are advised to verify the implementation of the decision by the importing or exporting country, as the case may be. HS codes Classification No Product description Classification considered rationale 1. Preparation, in the form of a powder, consisting of 92 % sugar, 6 % 2106.90 GRIs 1 and 6 black currant powder, anticaking agent, citric acid and black currant flavouring, put up for retail sale in 32-gram sachets, intended to be consumed as a beverage after mixing with hot water. 2. Vanutide cridificar (INN List 100). 3002.20 3. Certain INN products. Chapters 28, 29 (See “INN List 101” at the end of this publication.) and 30 4. Certain INN products. Chapters 13, 29 (See “INN List 102” at the end of this publication.) and 30 5. Certain INN products. Chapters 28, 29, (See “INN List 103” at the end of this publication.) 30, 35 and 39 6. Re-classification of INN products.
    [Show full text]
  • HEPP Report: Infectious Diseases in Corrections, Vol. 6 No. 6 HIV & Hepatitis Education Prison Project
    University of Rhode Island DigitalCommons@URI Infectious Diseases in Corrections Report (IDCR) 2003 HEPP Report: Infectious Diseases in Corrections, Vol. 6 No. 6 HIV & Hepatitis Education Prison Project Follow this and additional works at: http://digitalcommons.uri.edu/idcr Recommended Citation HIV & Hepatitis Education Prison Project, "HEPP Report: Infectious Diseases in Corrections, Vol. 6 No. 6" (2003). Infectious Diseases in Corrections Report (IDCR). Paper 46. http://digitalcommons.uri.edu/idcr/46 This Article is brought to you for free and open access by DigitalCommons@URI. It has been accepted for inclusion in Infectious Diseases in Corrections Report (IDCR) by an authorized administrator of DigitalCommons@URI. For more information, please contact [email protected]. HIV & HEPATITIS EDUCATION PRISON HEPJune 2003 Vol. 6, Issue 6 P REPORT PROJECT Infectious Diseases in Corrections SPONSOREDBYTHEBROWNMEDICALSCHOOLOFFICEOFCONTINUINGMEDICALEDUCATION. ABOUT HEPP Long-Term Toxicities Associated with HIV and HEPP Report, a forum for Antiretroviral Therapy correctional problem solving, targets correctional physicians, nurses, By Peter J. Piliero, M.D.*, Associate Professor of Medicine, Albany Medical College administrators, outreach workers, and Soon after the introduction of the first antiretroviraldine (3TC) have also been associated with pan- case managers. Published monthly (ARV) agent, zidovudine (AZT), drug-related toxi-creatitis. There may be an added potential for pan- and distributed by email and fax, cities became recognized and well-characterized.creatitis when using combinations of these nucle- HEPP Report provides up-to-the Things have since become more complicated;oside reverse transcriptase inhibitors (NRTIs). moment information HIV/AIDS, there are now 17 ARV agents in four distinct class-Importantly, the concomitant use of alcohol hepatitis, and other infectious es.
    [Show full text]
  • Screening of Clinically Approved and Investigation
    Screening of Clinically Approved and Investigation Drugs as Potential Inhibitors of SARS-CoV-2 Main Protease and Spike Receptor- Binding Domain Bound with ACE2 COVID19 Target Proteins: A Virtual Drug Repurposing Study Serdar Durdagi1,*, Busecan Aksoydan1,2, Berna Dogan1, Kader Sahin1, Aida Shahraki1,3, Necla Birgul-Iyison3 1Computational Biology and Molecular Simulations Laboratory, Department of Biophysics, School of Medicine, Bahcesehir University, Istanbul, Turkey 2Neuroscience Program, Graduate School of Health Sciences, Bahçeşehir University, Istanbul, Turkey 3Department of Molecular Biology and Genetics, Bogazici University, Istanbul, Turkey Abstract There is an urgent need for new drugs against COVID-19. Since designing a new drug and testing its pharmacokinetics and pharmacodynamics properties may take years, here we used a physics-driven high throughput virtual screening drug re-purposing approach to identify new compounds against COVID- 19. As the molecules considered in repurposing studies passed through several stages and have well- defined profiles, they would not require prolonged pre-clinical studies and hence, they would be excellent candidates in the cases of disease emergencies or outbreaks. While the Spike Protein is the key for the virus to enter the cell through the interaction with ACE2, enzymes such as main protease are crucial for the life cycle of the virus. These proteins are the most attractive targets for the development of new drugs against COVID-19 due to their pivotal roles in the fusion, replication and transcription of the virus. We used 7922 FDA approved small molecule drugs as well as compounds in clinical investigation from NIH Chemical Genomics Center (NCGC) Pharmaceutical Collection (NPC) database in our drug repurposing study.
    [Show full text]
  • This Project Has Been Supported with Unrestriced Grants from Abbvie Gilead Sciences HEXAL Janssen-Cilag MSD Viiv Healthcare By
    This project has been supported with unrestriced grants from AbbVie Gilead Sciences HEXAL Janssen-Cilag MSD ViiV Healthcare By Marcus Altfeld, Hamburg/Boston (USA) Achim Barmeyer, Dortmund Georg Behrens, Hannover Dirk Berzow, Hamburg Christoph Boesecke, Bonn Patrick Braun, Aachen Thomas Buhk, Hamburg Rob Camp, Barcelona (Spain/USA) Rika Draenert, Munich Christian Eggers, Linz (Austria) Stefan Esser, Essen Gerd Fätkenheuer, Cologne Gunar Günther, Windhoek (Namibia) Thomas Harrer, Erlangen Christian Herzmann, Borstel Christian Hoffmann, Hamburg Heinz-August Horst, Kiel Martin Hower, Dortmund Christoph Lange, Borstel Thore Lorenzen, Hamburg Tim Niehues, Krefeld Christian Noah, Hamburg Ramona Pauli, Munich Ansgar Rieke, Koblenz Jürgen Kurt Rockstroh, Bonn Thorsten Rosenkranz, Hamburg Bernhard Schaaf, Dortmund Ulrike Sonnenberg-Schwan, Munich Christoph D. Spinner, Munich Thomas Splettstoesser (Figures), Berlin Matthias Stoll, Hannover Hendrik Streeck, Essen/Boston (USA) Jan Thoden, Freiburg Markus Unnewehr, Dortmund Mechthild Vocks-Hauck, Berlin Jan-Christian Wasmuth, Bonn Michael Weigel, Schweinfurt Thomas Weitzel, Santiago (Chile) Eva Wolf, Munich HIV 2015/16 www.hivbook.com Edited by Christian Hoffmann and Jürgen K. Rockstroh Medizin Fokus Verlag IV Christian Hoffmann, M.D., Ph.D. ICH Stadtmitte (Infektionsmedizinisches Centrum Hamburg) Glockengiesserwall 1 20095 Hamburg, Germany Phone: + 49 40 2800 4200 Fax: + 49 40 2800 42020 [email protected] Jürgen K. Rockstroh, M.D., Ph.D. Department of Medicine I University of Bonn Sigmund-Freud-Strasse 25 53105 Bonn, Germany Phone: + 49 228 287 6558 Fax: + 49 228 287 5034 [email protected] HIV Medicine is an ever-changing field. The editors and authors of HIV 2015/16 have made every effort to provide information that is accurate and complete as of the date of publication.
    [Show full text]
  • Screening of Clinically Approved and Investigation Drugs As Potential
    Screening of Clinically Approved and Investigation Drugs as Potential Inhibitors of COVID-19 Main Protease: A Virtual Drug Repurposing Study Serdar Durdagi1,*, Busecan Aksoydan1,2, Berna Dogan1, Kader Sahin1, Aida Shahraki1,3 1Computational Biology and Molecular Simulations Laboratory, Department of Biophysics, School of Medicine, Bahcesehir University, Istanbul, Turkey 2Neuroscience Program, Graduate School of Health Sciences, Bahçeşehir University, Istanbul, Turkey 3Department of Molecular Biology and Genetics, Bogazici University, Istanbul, Turkey Abstract There is an urgent need for a new drug against COVID-19. Since designing a new drug and testing its pharmacokinetics and pharmacodynamics properties may take years, here we used a physics-driven high throughput virtual screening drug re-purposing approach to identify new compounds against COVID-19. As the molecules considered in repurposing studies passed through several stages and have well-defined profiles, they would not require prolonged pre- clinical studies and hence, they would be excellent candidates in the cases of disease emergencies or outbreaks. While the spike protein is the key for the virus to enter the cell though the interaction with ACE2, enzymes such as main protease are crucial for the life cycle of the virus. This protein is one of the most attractive targets for the development of new drugs against COVID-19 due to its pivotal role in the replication and transcription of the virus. We used 7922 FDA approved small molecule drugs as well as compounds in clinical investigation from NIH Chemical Genomics Center (NCGC) Pharmaceutical Collection (NPC) database in our drug repurposing study. Both apo and holo forms of target protein COVID-19 main proteases were used in virtual screening.
    [Show full text]
  • Background Paper 6.7 Human Immunodeficiency Virus (HIV)/ Acquired Immune Deficiency Syndromes (AIDS)
    Priority Medicines for Europe and the World "A Public Health Approach to Innovation" Update on 2004 Background Paper Written by Warren Kaplan Background Paper 6.7 Human Immunodeficiency Virus (HIV)/ Acquired Immune Deficiency Syndromes (AIDS) By Warren Kaplan, Ph.D., JD, MPH 15 February 2013 Update on 2004 Background Paper, BP 6.7 HIV/AIDS Table of Contents What is new since 2004? ..................................................................................................................................... 4 1. Introduction ................................................................................................................................................. 7 2. What are the Epidemiological Trends for Europe and the World? ................................................... 7 2.1 Western and Central Europe ............................................................................................................. 7 2.2 Eastern Europe .................................................................................................................................... 9 2.2 The World (including Europe) ........................................................................................................ 11 3. What is the Control Strategy? Is There an Effective Package of Control Methods Assembled into a “Control Strategy” for Most Epidemiological Settings?................................................................. 13 3.1 Is there a pharmaceutical ‘gap’? ....................................................................................................
    [Show full text]
  • Pdf Standard Procedure for Data Transfer
    STANDARD PROCEDURE FOR DATA TRANSFER Version 2.5 / June 2017 Contact: [email protected] www.iedea-sa.org / www.iedea-hiv.org IeDEA Southern Africa Standard Procedures for Data Transfer Contents 1 Introduction ........................................................................................................... 1 1.1 General remarks ....................................................................................................... 1 1.2 Inclusion criteria for patients ...................................................................................... 1 1.3 Dates ...................................................................................................................... 2 1.4 Definitions ............................................................................................................... 3 1.5 Standard codes ......................................................................................................... 3 1.6 Data tables .............................................................................................................. 3 2 Variables to be included in core tables ....................................................................... 6 2.1 Socio-demographic characteristics and outcomes (PAT table) ......................................... 6 2.2 Laboratory data (LAB table) .......................................................................................13 2.3 Antiretroviral drug variables (ART table) .....................................................................16 2.4
    [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]
  • Antiviral Drugs in the Treatment of Aids: What Is in the Pipeline ?
    October 15, 2007 EU RO PE AN JOUR NAL OF MED I CAL RE SEARCH 483 Eur J Med Res (2007) 12: 483-495 © I. Holzapfel Publishers 2007 ANTIVIRAL DRUGS IN THE TREATMENT OF AIDS: WHAT IS IN THE PIPELINE ? Hans-Jürgen Stellbrink Infektionsmedizinisches Centrum Hamburg ICH, Hamburg, Germany Abstract even targeting immune responses have to be devel- Drug development in the field of HIV treatment is oped. Continued drug development serves the ulti- rapid. New nucleoside analogues (NRTI), non-nucleo- mate goal of normalization of life expectancy. side analogue reverse transcriptase inhibitors (NNR- TI), and protease inhibitors (PI) are currently being in- METHODS vestigated in human trials. Furthermore, inhibitors of HIV attachment, fusion and integrase with novel Drug development in the field of HIV infection is modes of action are being developed, which offer new highly competitive, and a company’s decision to pur- perspectives for the goal of a normalization of life-ex- sue or discontinue the development of a drug is dri- pectancy in HIV-infected individuals. The most ad- ven by economic rather than scientific considerations. vanced compounds likely to become licensed soon in- Of all candidate compounds, only a few reach the lev- clude the NNRTIs rilpivirine and etravirine, the inte- el of trials in humans, and some exhibit lack of effica- grase inhibitors raltegravir and elvitegravir, and mar- cy or toxicity problems at this stage. Some compounds aviroc and vicriviroc, novel inhibitors of the CCR5 also have no obvious advantage over currently avail- chemokine receptor, which functions as the major able ones, so that their development is discontinued.
    [Show full text]
  • Hoffmann Rockstroh |
    Hoffmann| Rockstroh HIV 2015/2016 www.hivbook.com Medizin Fokus Verlag This project has been supported with unrestriced grants from AbbVie Gilead Sciences HEXAL Janssen-Cilag MSD ViiV Healthcare By Marcus Altfeld, Hamburg/Boston (USA) Achim Barmeyer, Dortmund Georg Behrens, Hannover Dirk Berzow, Hamburg Christoph Boesecke, Bonn Patrick Braun, Aachen Thomas Buhk, Hamburg Rob Camp, Barcelona (Spain/USA) Rika Draenert, Munich Christian Eggers, Linz (Austria) Stefan Esser, Essen Gerd Fätkenheuer, Cologne Gunar Günther, Windhoek (Namibia) Thomas Harrer, Erlangen Christian Herzmann, Borstel Christian Hoffmann, Hamburg Heinz-August Horst, Kiel Martin Hower, Dortmund Christoph Lange, Borstel Thore Lorenzen, Hamburg Tim Niehues, Krefeld Christian Noah, Hamburg Ramona Pauli, Munich Ansgar Rieke, Koblenz Jürgen Kurt Rockstroh, Bonn Thorsten Rosenkranz, Hamburg Bernhard Schaaf, Dortmund Ulrike Sonnenberg-Schwan, Munich Christoph D. Spinner, Munich Thomas Splettstoesser (Figures), Berlin Matthias Stoll, Hannover Hendrik Streeck, Essen/Boston (USA) Jan Thoden, Freiburg Markus Unnewehr, Dortmund Mechthild Vocks-Hauck, Berlin Jan-Christian Wasmuth, Bonn Michael Weigel, Schweinfurt Thomas Weitzel, Santiago (Chile) Eva Wolf, Munich HIV 2015/16 www.hivbook.com Edited by Christian Hoffmann and Jürgen K. Rockstroh Medizin Fokus Verlag IV Christian Hoffmann, M.D., Ph.D. ICH Stadtmitte (Infektionsmedizinisches Centrum Hamburg) Glockengiesserwall 1 20095 Hamburg, Germany Phone: + 49 40 2800 4200 Fax: + 49 40 2800 42020 [email protected] Jürgen K. Rockstroh, M.D., Ph.D. Department of Medicine I University of Bonn Sigmund-Freud-Strasse 25 53105 Bonn, Germany Phone: + 49 228 287 6558 Fax: + 49 228 287 5034 [email protected] HIV Medicine is an ever-changing field. The editors and authors of HIV 2015/16 have made every effort to provide information that is accurate and complete as of the date of publication.
    [Show full text]
  • WO 2014/184553 Al 20 November 2014 (20.11.2014) 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 2014/184553 Al 20 November 2014 (20.11.2014) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 31/34 (2006.01) A61K 31/535 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K 31/427 (2006.01) A61P 31/18 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, A61K 31/513 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (21) International Application Number: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, PCT/GB20 14/05 1478 KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, (22) International Filing Date: MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, 14 May 2014 (14.05.2014) OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, (25) Filing Language: English TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, (26) Publication Language: English ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 1749/MUM/2013 15 May 2013 (15.05.2013) IN kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, (71) Applicant: CIPLA LIMITED [—/IN]; Cipla House, Pen UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, insula Business Park, Ganpatrao Kadam Marg, Lower TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, Parel, Mumbai-400 013 (IN).
    [Show full text]