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E30 SEM. O.C. Disclosed Is a Compound Represented by the Formula (1) (51) Int

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USOO9453000B2 (12) United States Patent (10) Patent No.: US 9.453,000 B2 Kimura et al. (45) Date of Patent: *Sep. 27, 2016 (54) POLYCYCLIC COMPOUND (56) References Cited (75) Inventors: Teiji Kimura, Tsukuba (JP); Noritaka U.S. PATENT DOCUMENTS Kitazawa, Tsukuba (JP); Toshihiko 3,470,167 A 9, 1969 Sarkar Kaneko, Tsukuba (JP); Nobuaki Sato, 3,989,816 A 1 1/1976 Rajadhyaksha Tsukuba (JP); Koki Kawano, Tsukuba 4,910,200 A 3, 1990 Curtze et al. (JP): Koichi Ito, Tsukuba (JP); 5,281,626 A 1/1994 Oinuma et al. M s Tak ishi Tsukub JP 5,563,162 A 10, 1996 Oku et al. amoru Takaishi Tsukuba (JP); 5,804,577 A 9, 1998 Hebeisen et al. Takeo Sasaki, Tsukuba (JP); Yu 5,985,856 A 11/1999 Stella et al. Yoshida, Tsukuba (JP); Toshiyuki 6,235,728 B1 5, 2001 Golik et al. Uemura, Tsukuba (JP); Takashi Doko, g R 1939. E. al. Its SE E. Shinmyo, 7,138.414 B2 11/2006 Schoenafingereatch et al. et al. sukuba (JP); Daiju Hasegawa, 7,300,936 B2 11/2007 Parker et al. Tsukuba (JP); Takehiko Miyagawa, 7,314,940 B2 1/2008 Graczyk et al. Hatfield (GB); Hiroaki Hagiwara, 7,618,960 B2 11/2009 Kimura et al. Tsukuba (JP) 7,667,041 B2 2/2010 Kimura et al. 7,687,640 B2 3/2010 Kimura et al. 7,713,993 B2 5/2010 Kimura et al. (73) Assignee: EISAI R&D MANAGEMENT CO., 7,737,141 B2 6/2010 Kimura et al. LTD., Tokyo (JP) 7,880,009 B2 2/2011 Kimura et al. 7,897,632 B2 3/2011 Kimura et al. (*) Notice: Subject to any disclaimer, the term of this 7,935,815 B2 5/2011 Kimura et al. patent is extended or adjusted under 35 SS R: 38H SA U.S.C. 154(b) by 1597 days. 8,048,878www. B2 11/2011 KimuraUa et al.a This patent is Subject to a terminal dis- 2001/0051642 A1 12/2001 Ahn et al. claimer. 2002/O128263 A1 9, 2002 Mutel et al. (Continued) (21) Appl. No.: 12/671,873 FOREIGN PATENT DOCUMENTS (22) PCT Filed: Aug. 28, 2008 CN 1668593. A 9, 2005 (86). PCT No.: PCT/UP2008/065.365 DE 3541716 A1 5, 1987 S 371 (c)(1), (Continued)Continued (2), (4) Date: Sep. 23, 2010 OTHER PUBLICATIONS (87) PCT Pub. No.: WO2009/028588 Communication pursuant to Article 94(3) EPC issued Jul. 30, 2013 in European Patent Application No. 05743758.4. PCT Pub. Date: Mar. 5, 2009 (Continued) (65) Prior Publication Data US 2011 FOOO9619 A1 Jan. 13, 2011 Primary Examiner — Susanna Moore (74) Attorney, Agent, or Firm — Birch, Stewart, Kolasch & (30) Foreign Application Priority Data Birch, LLP Aug. 31, 2007 (JP) ................................. 2007-225045 (57) ABSTRACT E30 SEM. O.C. Disclosed is a compound represented by the formula (1) (51) Int. Cl. (I) CO7D 47L/04 (2006.01) A6 IK 3/437 (2006.01) G) ()-X-G) CO7D 487/04 (2006.01) CO7D 49.8/04 (2006.01) CO7D 403/0 (2006.01) or a pharmacologically acceptable salt thereof, which is A61 P 25/28 (2006.01) effective as a therapeutic or prophylactic agent for a disease CO7D 403/04 (2006.01) induced by AB, wherein Ari represents an imidazolyl group (52) U.S. Cl. which may be substituted with a C1-6 alkyl group, or the CPC ........... C07D 403/10 (2013.01); C07D 471/04 like; Ara represents a phenyl group which may be substituted (2013.01); C07D 487/04 (2013.01); C07D with a C1-6 alkoxy group, or the like: X represents a double 498/04 (2013.01) bond, or the like; and Het represents a triazolyl group or the (58) Field of Classification Search like which may be substituted with a C1-6 alkyl group or the CPC ........................... A61K 31/437; C07D 471/04 like, or the like. 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    Turkish Journal of Chemistry Turk J Chem (2018) 42: 1191 – 1216 http://journals.tubitak.gov.tr/chem/ © TÜBİTAK Research Article doi:10.3906/kim-1709-4 Tetrahydropyridine: a promising heterocycle for pharmacologically active molecules Noor-ul-Amin MOHSIN1,, Matloob AHMAD2;∗, 1Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, Pakistan 2Department of Chemistry, Government College University, Faisalabad, Pakistan Received: 05.09.2017 • Accepted/Published Online: 08.05.2018 • Final Version: 11.10.2018 Abstract: The tetrahydropyridine (THP) ring system has received considerable focus due to its excellent ability to act as a pharmacophore. It is recognized as a major constituent in natural alkaloids. THP derivatives have been reported for a diverse range of biological activities. Recent synthetic works contain syntheses of monosubstituted, disubstituted, trisubstituted, highly functionalized, and condensed structures. In this review, we summarize the recent literature dealing with the bioactive nature of this important heterocycle. Key words: Functionalized tetrahydropyridine, condensed tetrahydropyridine, multicomponent reaction, antimicrobial, antiinflammatory, anticancer, tryptamine receptor agonist, muscarinic receptor agonist, enzyme inhibitors 1. Introduction Biologically active heterocyclic compounds are abundantly found in nature. 1 Among heterocyclic compounds, pyridine and partially reduced dihydropyridine and tetrahydropyridine (THP) have emerged as excellent tem- plates for various bioactive molecules. 2;3 Three structural isomers of THP are 1,2,3,6-tetrahydropyridine, 1,2,3,4- tetrahydropyridine, and 3,4,5,6-tetrahydropyridine. Arecoline and betanin III are the two natural biologically active THP compounds containing alkaloid and glycoside, respectively. 4−6 The most famous THP-containing neurotoxin is 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine, which causes parkinsonism disease.
  • Pharmaceutical Appendix to the Tariff Schedule 2

    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
  • Equilibrium Assays Are Required to Accurately Characterize the Activity Profiles of Drugs

    Equilibrium Assays Are Required to Accurately Characterize the Activity Profiles of Drugs

    Molecular Pharmacology Fast Forward. Published on June 28, 2018 as DOI: 10.1124/mol.118.112573 This article has not been copyedited and formatted. The final version may differ from this version. MOL112573 Equilibrium Assays are Required to Accurately Characterize the Activity Profiles of Drugs Modulating Gq-Coupled GPCRs Sara Bdioui, Julien Verdi, Nicolas Pierre, Eric Trinque, Thomas Roux, Terry Kenakin SB, JV, NP, ET, TR: Cisbio Bioassays, 30200 Codolet, France TK : Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina Downloaded from molpharm.aspetjournals.org at ASPET Journals on September 26, 2021 1 Molecular Pharmacology Fast Forward. Published on June 28, 2018 as DOI: 10.1124/mol.118.112573 This article has not been copyedited and formatted. The final version may differ from this version. MOL112573 RUNNING (SHORT) TITLE Functional assays for Gq Protein activating Receptor Ligands Corresponding author: Terry Kenakin Ph.D. Professor, Department of Pharmacology University of North Carolina School of Medicine Downloaded from 120 Mason Farm Road Room 4042 Genetic Medicine Building, CB# 7365 molpharm.aspetjournals.org Chapel Hill, NC 27599-7365 Phone: 919-962-7863 Fax: 919-966-7242 or 5640 Email: [email protected] at ASPET Journals on September 26, 2021 Number of text pages: 56 Number of tables: 0 Number of figures: 13 Number of references: 33 Number of words in the Abstract: 233 Number of words in the Introduction: 599 Number of words in the Discussion: 1497 2 Molecular Pharmacology Fast Forward. Published on June 28, 2018 as DOI: 10.1124/mol.118.112573 This article has not been copyedited and formatted.