DOCSLIB.ORG

WO 2015/006592 Al 15 January 2015 (15.01.2015) P O P C T

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
WO 2015/006592 Al 15 January 2015 (15.01.2015) 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 2015/006592 Al 15 January 2015 (15.01.2015) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C07D 401/14 (2006.01) C07D 417/12 (2006.01) kind of national protection available): AE, AG, AL, AM, C07D 401/04' (2006.01) C07D 417/14 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, C07D 401/12 (2006.01) C07D 251/18 (2006.01) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, C07D 403/12 (2006.01) A61K 31/53 (2006.01) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, C07D 403/04' (2006.01) A61P 35/00 (2006.01) HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, C07D 413/12 (2006.01) KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (21) International Application Number: OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, PCT/US20 14/046204 SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, (22) International Filing Date: TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, 10 July 2014 (10.07.2014) ZW. (25) Filing Language: English (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (26) Publication Language: English GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, (30) Priority Data: UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, 61/845,352 11 July 2013 ( 11.07.2013) US TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, FT, LT, LU, LV, (71) Applicant: AGIOS PHARMACEUTICALS, INC. MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, [US/US]; 38 Sidney Street, Cambridge, MA 02139 (US). TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). (72) Inventors: TRAVINS, Jeremy; 59 Flagg Road, Southbor- ough, MA 01772 (US). UTLEY, Luke; 652 Rte 13 S., Published: Milford, NH 03055 (US). — with international search report (Art. 21(3)) (74) Agent: GEORGES EVANGELINOS, Asimina, T.; Lando & Anastasi LLP, Riverfront Office Park, One Main Street, Suite 1100, Cambridge, MA 02142 (US). (54) Title: N,6-BIS(ARYL OR HETEROARYL)-l,3,5-TRIAZINE-2,4-DIAMINE COMPOUNDS AS IDH2 MUTANTS INHIBIT ORS FOR THE TREATMENT OF CANCER (I), i ©o © (57) Abstract: Provided are compounds of formula (I), Wherein: ring A and ring B are each independently an optionally substituted 5-6 membered monocyclic aryl or heteroaryl. The compounds are inhibitors of isocitrate dehydrogenase 2 (IDH2) mutants useful for Q treating cancer. N,6-BIS(ARYL OR HETEROARYL)-1 ,3,5-TRIAZINE-2,4-DIAMINE COMPOUNDS AS IDH2 MUTANTS INHIBITORS FOR THE TREATMENT OF CANCER CLAIM OF PRIORITY This application claims priority from U.S. Application Serial No. 61/845352 filed July 11, 2013, which is incorporated herein by reference in its entirety. BACKGROUND OF INVENTION Isocitrate dehydrogenases (IDHs) catalyze the oxidative decarboxylation of isocitrate to 2-oxoglutarate (i.e., a-ketoglutarate). These enzymes belong to two distinct subclasses, one of which utilizes NAD(+) as the electron acceptor and the other NADP(+). Five isocitrate dehydrogenases have been reported: three NAD(+)-dependent isocitrate dehydrogenases, which localize to the mitochondrial matrix, and two NADP(+)-dependent isocitrate dehydrogenases, one of which is mitochondrial and the other predominantly cytosolic. Each NADP(+)-dependent isozyme is a homodimer. IDH2 (isocitrate dehydrogenase 2 (NADP+), mitochondrial) is also known as IDH; IDP; IDHM; IDPM; ICD-M; or mNADP-IDH. The protein encoded by this gene is the NADP(+)-dependent isocitrate dehydrogenase found in the mitochondria. It plays a role in intermediary metabolism and energy production. This protein may tightly associate or interact with the pyruvate dehydrogenase complex. Human IDH2 gene encodes a protein of 452 amino acids. The nucleotide and amino acid sequences for IDH2 can be found as GenBank entries NM_002168.2 and NP_002159.2 respectively. The nucleotide and amino acid sequence for human IDH2 are also described in, e.g., Huh et al., Submitted (NOV-1992) to the EMBL/GenBank/DDBJ databases; and The MGC Project Team, Genome Res. 14:2121-2127(2004). Non-mutant, e.g., wild type, IDH2 catalyzes the oxidative decarboxylation of isocitrate to a-ketoglutarate (a-KG) thereby reducing NAD+ (NADP+) to NADH (NADPH), e.g., in the forward reaction: + + → + Isocitrate + NAD (NADP ) a-KG + C0 2 + NADH (NADPH) + H . It has been discovered that mutations of IDH2 present in certain cancer cells result in a new ability of the enzyme to catalyze the NAPH-dependent reduction of α-ketoglutarate to R (-)-2-hydroxyglutarate (2HG). 2HG is not formed by wild-type IDH2. The production of 2HG is believed to contribute to the formation and progression of cancer (Dang, L et al, Nature 2009, 462:739-44). The inhibition of mutant IDH2 and its neoactivity is therefore a potential therapeutic treatment for cancer. Accordingly, there is an ongoing need for inhibitors of IDH2 mutants having alpha hydroxyl neoactivity. SUMMARY OF INVENTION Described herein are compounds of Structural Formula I, or a pharmaceutically acceptable salt or hydrate thereof: wherein: ring A is an optionally substituted 5-6 member monocyclic aryl or monocyclic heteroaryl; and ring B is an optionally substituted 5-6 member monocyclic aryl or monocyclic heteroaryl; wherein: a. ring A and ring B are not both an optionally substituted 6 member monocyclic aryl; b. when ring A is unsubstituted pyridyl, then ring B is not phenyl optionally substituted with one to three groups independently selected from methyl, ethyl, t- butyl, methoxy, CH(OH)CH 3, CI, Br, SH, and CF3; c. when ring A is a 5-membered heteroaryl, then ring B is not phenyl optionally substituted with one to two groups independently selected from F, CI, S0 2CH3, C(0)OCH , methyl, ethyl, t-butyl, methoxy, ethoxy, O-phenyl, CF , OH, and NO2; d. when ring A is a 2,4-di-substituted 5-thiazolyl, then ring B is not substituted phenyl; e. the compound is not: (1) V -2-pyridinyl-6-(3-pyridinyl)- ,3,5-triazine-2,4-diamine; (2) 6-(6-methoxy-3-pyridinyl)-N2-(4-methylphenyl)-l,3,5-triazine-2,4- diamine; (3) 6-(2-methoxy-3-pyridinyl)-N2-(4-methylphenyl)-l,3,5-triazine-2,4- diamine; (4) N2-(3-chlorophenyl)-6-(2-chloro-4-pyridinyl)-l,3,5-triazine-2,4-diamine; (5) 3-[[4-[4-amino-6-[(3-chlorophenyl)amino]-l,3,5-triazin-2-yl]-2- pyridinyl]amino]-1-propanol; (6) N-[3-[[4-amino-6-(2-methyl-4-pyrimidinyl)-l,3,5-triazin-2-yl]amino]-4- methylphenyl]-N'-[4-chloro-3-(trifluoromethyl)phenyl]-urea; (7) N4,N4'-diphenyl-[2,2'-bi-l,3,5-triazine]-4,4 ,,6,6,-tetramine; (8) 6,6'-(2,6-pyridinediyl)bis[N-phenyl-l,3,5-triazine-2,4-diamine; or (9) 6,6'-(2,3-pyrazinediyl)bis[N-phenyl-l,3,5-triazine-2,4-diamine. The compound of Formula I or II or as described in any one of the embodiments herein inhibits mutant IDH2, particularly mutant IDH2 having alpha hydroxyl neoactivity. Also described herein are pharmaceutical compositions comprising a compound of Formula I and methods of using such compositions to treat cancers characterized by the presence of a mutant IDH2. DETAILED DESCRIPTION The details of construction and the arrangement of components set forth in the following description or illustrated in the drawings are not meant to be limiting. Other embodiments and different ways to practice the invention are expressly included. Also, the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The use of "including," "comprising," or "having," "containing", "involving", and variations thereof herein, is meant to encompass the items listed thereafter and equivalents thereof as well as additional items. Definitions: The term "halo" or "halogen" refers to any radical of fluorine, chlorine, bromine or iodine. The term "alkyl" refers to a fully saturated or unsaturated hydrocarbon chain that may be a straight chain or branched chain, containing the indicated number of carbon atoms. For example, C C12 alkyl indicates that the group may have from 1 to 12 (inclusive) carbon atoms in it. The term "haloalkyl" refers to an alkyl in which one or more hydrogen atoms are replaced by halo, and includes alkyl moieties in which all hydrogens have been replaced by halo (e.g., perfluoroalkyl). The terms "arylalkyl" or "aralkyl" refer to an alkyl moiety in which an alkyl hydrogen atom is replaced by an aryl group. Aralkyl includes groups in which more than one hydrogen atom has been replaced by an aryl group. Examples of "arylalkyl" or "aralkyl" include benzyl, 2-phenylethyl, 3-phenylpropyl, 9-fluorenyl, benzhydryl, and trityl groups. The term "alkyl" includes "alkenyl" and "alkynyl". The term "alkylene" refers to a divalent alkyl, e.g., -CH2-, -CH2CH2-, -CH2CH2CH2- and -CH2CH(CH3)CH2-. The term "alkenyl" refers to a straight or branched hydrocarbon chain containing 2-12 carbon atoms and having one or more double bonds. Examples of alkenyl groups include, but are not limited to, allyl, propenyl, 2-butenyl, 3-hexenyl and 3-octenyl groups. One of the double bond carbons may optionally be the point of attachment of the alkenyl substituent.
Load more

Recommended publications
  • (12) United States Patent (10) Patent No.: US 8,999,632 B2 Falcon Et Al
    US008.999632B2 (12) United States Patent (10) Patent No.: US 8,999,632 B2 Falcon et al. (45) Date of Patent: Apr. 7, 2015 (54) METHOD FOR MEASURING ATR (52) U.S. Cl. INHIBITION MEDIATED INCREASES IN DNA CPC ............ G0IN33/5047 (2013.01); G0IN33/68 DAMAGE (2013.01) (58) Field of Classification Search (71) Applicants: Vertex Pharmaceuticals Incorporated, USPC ........................................................ 435/2, 15 Cambridge, MA (US); University of See application file for complete search history. Newcastle Upon Tyne, Newcastle Upon Tyne (GB) (56) References Cited (72) Inventors: Susanna Falcon, Newbury (GB); Philip PUBLICATIONS Reaper, Shillingford (GB); John Kao et al. Inhibition of Gamma-H2AXAfter Ionizing Radiation. As a Pollard, Abingdon (GB); Nicola Curtin, Biological Surrogate of Impaired Upstream DNA Damage Signaling Newcastle upon Tyne (GB); Fiona and Radiosensitivity; Journal of Cancer Molecules, vol. 5, No. 2 Middleton, South Gosforth (GB); Tao (2010) pp. 49-54.* Chen, Suzhou (CN) Buscemi, G., et al., “DNA Damage-Induced Cell Cycle Regulation of Novel Chk2 Phosphoresidues'. Molecular and Cellular Biology, (73) Assignee: Vertex Pharmaceuticals Incorporated, 26(21), (2006), pp. 7832-7845 (DOI: 10.1128/MCB.00534-06). Boston, MA (US) Chen, T., et al., “Targeting the S and G2 checkpoint to treat cancer. s Drug Discovery Today, 17(5/6), (2012), pp. 194-202, (DOI: 10.1016/ - r - j.drudis.2011, 12.009). (*) Notice: Subject to any disclaimer, the term of this Chen, T., et al., “Development of a biomarker of ATR activity in patent is extended or adjusted under 35 surrogate human tissues”, Newcastle University, Poster, Nov. 2012. U.S.C. 154(b) by 0 days.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 6,264,917 B1 Klaveness Et Al
    USOO6264,917B1 (12) United States Patent (10) Patent No.: US 6,264,917 B1 Klaveness et al. (45) Date of Patent: Jul. 24, 2001 (54) TARGETED ULTRASOUND CONTRAST 5,733,572 3/1998 Unger et al.. AGENTS 5,780,010 7/1998 Lanza et al. 5,846,517 12/1998 Unger .................................. 424/9.52 (75) Inventors: Jo Klaveness; Pál Rongved; Dagfinn 5,849,727 12/1998 Porter et al. ......................... 514/156 Lovhaug, all of Oslo (NO) 5,910,300 6/1999 Tournier et al. .................... 424/9.34 FOREIGN PATENT DOCUMENTS (73) Assignee: Nycomed Imaging AS, Oslo (NO) 2 145 SOS 4/1994 (CA). (*) Notice: Subject to any disclaimer, the term of this 19 626 530 1/1998 (DE). patent is extended or adjusted under 35 O 727 225 8/1996 (EP). U.S.C. 154(b) by 0 days. WO91/15244 10/1991 (WO). WO 93/20802 10/1993 (WO). WO 94/07539 4/1994 (WO). (21) Appl. No.: 08/958,993 WO 94/28873 12/1994 (WO). WO 94/28874 12/1994 (WO). (22) Filed: Oct. 28, 1997 WO95/03356 2/1995 (WO). WO95/03357 2/1995 (WO). Related U.S. Application Data WO95/07072 3/1995 (WO). (60) Provisional application No. 60/049.264, filed on Jun. 7, WO95/15118 6/1995 (WO). 1997, provisional application No. 60/049,265, filed on Jun. WO 96/39149 12/1996 (WO). 7, 1997, and provisional application No. 60/049.268, filed WO 96/40277 12/1996 (WO). on Jun. 7, 1997. WO 96/40285 12/1996 (WO). (30) Foreign Application Priority Data WO 96/41647 12/1996 (WO).
    [Show full text]
  • Ep 2569287 B1
    (19) TZZ _T (11) EP 2 569 287 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: C07D 413/04 (2006.01) C07D 239/46 (2006.01) 09.07.2014 Bulletin 2014/28 (86) International application number: (21) Application number: 11731562.2 PCT/US2011/036245 (22) Date of filing: 12.05.2011 (87) International publication number: WO 2011/143425 (17.11.2011 Gazette 2011/46) (54) COMPOUNDS USEFUL AS INHIBITORS OF ATR KINASE VERBINDUNGEN ALS HEMMER DER ATR-KINASE COMPOSÉS UTILISABLES EN TANT QU’INHIBITEURS DE LA KINASE ATR (84) Designated Contracting States: • VIRANI, Aniza, Nizarali AL AT BE BG CH CY CZ DE DK EE ES FI FR GB Abingdon GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO Oxfordshire OX144RY (GB) PL PT RO RS SE SI SK SM TR • REAPER, Philip, Michael Abingdon (30) Priority: 12.05.2010 US 333869 P Oxfordshire OX144RY (GB) (43) Date of publication of application: (74) Representative: Coles, Andrea Birgit et al 20.03.2013 Bulletin 2013/12 Kilburn & Strode LLP 20 Red Lion Street (73) Proprietor: Vertex Pharmaceuticals Inc. London WC1R 4PJ (GB) Boston, MA 02210 (US) (56) References cited: (72) Inventors: WO-A1-2010/054398 WO-A1-2010/071837 • CHARRIER, Jean-Damien Abingdon • C. A. HALL-JACKSON: "ATR is a caffeine- Oxfordshire OX144RY (GB) sensitive, DNA-activated protein kinase with a • DURRANT, Steven, John substrate specificity distinct from DNA-PK", Abingdon ONCOGENE, vol. 18, 1999, pages 6707-6713, Oxfordshire OX144RY (GB) XP002665425, cited in the application • KNEGTEL, Ronald, Marcellus Alphonsus Abingdon Oxfordshire OX144RY (GB) Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations.
    [Show full text]
  • Section B Changed Classes/Guidelines Final
    EPHMRA ANATOMICAL CLASSIFICATION GUIDELINES 2019 Section B Changed Classes/Guidelines Final Version Date of issue: 24th December 2018 1 A3 FUNCTIONAL GASTRO-INTESTINAL DISORDER DRUGS R2003 A3A PLAIN ANTISPASMODICS AND ANTICHOLINERGICS R1993 Includes all plain synthetic and natural antispasmodics and anticholinergics. A3B Out of use; can be reused. A3C ANTISPASMODIC/ATARACTIC COMBINATIONS This group includes combinations with tranquillisers, meprobamate and/or barbiturates except when they are indicated for disorders of the autonomic nervous system and neurasthenia, in which case they are classified in N5B4. A3D ANTISPASMODIC/ANALGESIC COMBINATIONS R1997 This group includes combinations with analgesics. Products also containing either tranquillisers or barbiturates and analgesics to be also classified in this group. Antispasmodics indicated exclusively for dysmenorrhoea are classified in G2X1. A3E ANTISPASMODICS COMBINED WITH OTHER PRODUCTS r2011 Includes all other combinations not specified in A3C, A3D and A3F. Combinations of antispasmodics and antacids are classified in A2A3; antispasmodics with antiulcerants are classified in A2B9. Combinations of antispasmodics with antiflatulents are classified here. A3F GASTROPROKINETICS r2013 This group includes products used for dyspepsia and gastro-oesophageal reflux. Compounds included are: alizapride, bromopride, cisapride, clebopride, cinitapride, domperidone, levosulpiride, metoclopramide, trimebutine. Prucalopride is classified in A6A9. Combinations of gastroprokinetics with other substances
    [Show full text]
  • Marrakesh Agreement Establishing the World Trade Organization
    No. 31874 Multilateral Marrakesh Agreement establishing the World Trade Organ ization (with final act, annexes and protocol). Concluded at Marrakesh on 15 April 1994 Authentic texts: English, French and Spanish. Registered by the Director-General of the World Trade Organization, acting on behalf of the Parties, on 1 June 1995. Multilat ral Accord de Marrakech instituant l©Organisation mondiale du commerce (avec acte final, annexes et protocole). Conclu Marrakech le 15 avril 1994 Textes authentiques : anglais, français et espagnol. Enregistré par le Directeur général de l'Organisation mondiale du com merce, agissant au nom des Parties, le 1er juin 1995. Vol. 1867, 1-31874 4_________United Nations — Treaty Series • Nations Unies — Recueil des Traités 1995 Table of contents Table des matières Indice [Volume 1867] FINAL ACT EMBODYING THE RESULTS OF THE URUGUAY ROUND OF MULTILATERAL TRADE NEGOTIATIONS ACTE FINAL REPRENANT LES RESULTATS DES NEGOCIATIONS COMMERCIALES MULTILATERALES DU CYCLE D©URUGUAY ACTA FINAL EN QUE SE INCORPOR N LOS RESULTADOS DE LA RONDA URUGUAY DE NEGOCIACIONES COMERCIALES MULTILATERALES SIGNATURES - SIGNATURES - FIRMAS MINISTERIAL DECISIONS, DECLARATIONS AND UNDERSTANDING DECISIONS, DECLARATIONS ET MEMORANDUM D©ACCORD MINISTERIELS DECISIONES, DECLARACIONES Y ENTEND MIENTO MINISTERIALES MARRAKESH AGREEMENT ESTABLISHING THE WORLD TRADE ORGANIZATION ACCORD DE MARRAKECH INSTITUANT L©ORGANISATION MONDIALE DU COMMERCE ACUERDO DE MARRAKECH POR EL QUE SE ESTABLECE LA ORGANIZACI N MUND1AL DEL COMERCIO ANNEX 1 ANNEXE 1 ANEXO 1 ANNEX
    [Show full text]
  • WO 2012/089768 Al 5 July 2012 (05.07.2012) 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 2012/089768 Al 5 July 2012 (05.07.2012) P O P C T (51) International Patent Classification: (74) Agent: CARPINTERO LOPEZ, Francisco; Herrero & A61K 47/48 (2006.01) A61P 35/00 (2006.01) Asociados, S.L., Alcala, 35, E-280014 Madrid (ES). (21) International Application Number: (81) Designated States (unless otherwise indicated, for every PCT/EP20 11/074150 kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, (22) International Filing Date: CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, 28 December 201 1 (28. 12.201 1) DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, (25) Filing Language: English HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, (26) Publication Language: English MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (30) Priority Data: OM, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SC, SD, P201031 971 28 December 2010 (28. 12.2010) ES 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 (for all designated States except US): ENDOR NANOTECHNOLOGIES, S.L. [ES/ES]; Edificio Helix - (84) Designated States (unless otherwise indicated, for every c/ Baldiri Reixac, 15, E-08028 Barcelona (ES).
    [Show full text]
  • Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DIX to the HTSUS—Continued
    20558 Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DEPARMENT OF THE TREASURY Services, U.S. Customs Service, 1301 TABLE 1.ÐPHARMACEUTICAL APPEN- Constitution Avenue NW, Washington, DIX TO THE HTSUSÐContinued Customs Service D.C. 20229 at (202) 927±1060. CAS No. Pharmaceutical [T.D. 95±33] Dated: April 14, 1995. 52±78±8 ..................... NORETHANDROLONE. A. W. Tennant, 52±86±8 ..................... HALOPERIDOL. Pharmaceutical Tables 1 and 3 of the Director, Office of Laboratories and Scientific 52±88±0 ..................... ATROPINE METHONITRATE. HTSUS 52±90±4 ..................... CYSTEINE. Services. 53±03±2 ..................... PREDNISONE. 53±06±5 ..................... CORTISONE. AGENCY: Customs Service, Department TABLE 1.ÐPHARMACEUTICAL 53±10±1 ..................... HYDROXYDIONE SODIUM SUCCI- of the Treasury. NATE. APPENDIX TO THE HTSUS 53±16±7 ..................... ESTRONE. ACTION: Listing of the products found in 53±18±9 ..................... BIETASERPINE. Table 1 and Table 3 of the CAS No. Pharmaceutical 53±19±0 ..................... MITOTANE. 53±31±6 ..................... MEDIBAZINE. Pharmaceutical Appendix to the N/A ............................. ACTAGARDIN. 53±33±8 ..................... PARAMETHASONE. Harmonized Tariff Schedule of the N/A ............................. ARDACIN. 53±34±9 ..................... FLUPREDNISOLONE. N/A ............................. BICIROMAB. 53±39±4 ..................... OXANDROLONE. United States of America in Chemical N/A ............................. CELUCLORAL. 53±43±0
    [Show full text]
  • Nitrile SKIN2 DECOUVREZ VOTRE 2Ième PEAU
    NITRILE SKIN2 DECOUVREZ VOTRE 2IÈME PEAU PROTECTION CONTRE LES INFECTIONS – imperméable aux virus pour l’utilisateur et le patient EXCELLENTE SENSIBILITE TACTILE – grâce à une épaisseur optimisée PORT TRES CONFORTABLE – grâce au matériau souple novateur tre les on inf t très c c e or on n nte sen c P fo e si ti xemp r io ll b o E t d t t e il n e a c c i b t s l x é e a l e t E t t e o a x r c t n P i l a e t u r e l nitrile skin 2 EXAMINATION GLOVES BY SEMPERMED INFORMATION PRODUITS PROTECTION GANTS 8/3/2012 8/3/2012 RecommandationsRecommandations à propos de la résistance à proposINFORMATIONS aux de la résistance Sempermed® aux produits chimiquesproduits chimiques «Manipulation de produits chimiques en milieu hospitalier avec les gants nitrile Sempercare® 08/03/2012 Les gants de protection àLes usage gants unique de protectionSempercare® à usageont uniqueété contrôlés Sempercare® ont été contrôlés conformémentRecommandations aux exigences à propos deconformément la denorme la résistance EN aux 374-3 exigences aux « produits détermination de chimiques la norme de laEN résistance 374-3 « détermination de la résistance à la perméationLes gants par de desprotection produits àà usage la chimiques perméation unique Sempercare®». par des produits ont été contrôlés chimiques conformément ». aux exigences de la norme EN 374-3 « détermination de la résistance à la perméation par des produits chimiques ». Sempercare® Sempercare® Sempercare® Sempercare® Produit chimique Sempercare®Produit chimique Sempercare® Sempercare® Sempercare® Latex sans
    [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]
  • I (Acts Whose Publication Is Obligatory) COMMISSION
    13.4.2002 EN Official Journal of the European Communities L 97/1 I (Acts whose publication is obligatory) COMMISSION REGULATION (EC) No 578/2002 of 20 March 2002 amending Annex I to Council Regulation (EEC) No 2658/87 on the tariff and statistical nomenclature and on the Common Customs Tariff THE COMMISSION OF THE EUROPEAN COMMUNITIES, Nomenclature in order to take into account the new scope of that heading. Having regard to the Treaty establishing the European Commu- nity, (4) Since more than 100 substances of Annex 3 to the Com- bined Nomenclature, currently classified elsewhere than within heading 2937, are transferred to heading 2937, it is appropriate to replace the said Annex with a new Annex. Having regard to Council Regulation (EEC) No 2658/87 of 23 July 1987 on the tariff and statistical nomenclature and on the Com- mon Customs Tariff (1), as last amended by Regulation (EC) No 2433/2001 (2), and in particular Article 9 thereof, (5) Annex I to Council regulation (EEC) No 2658/87 should therefore be amended accordingly. Whereas: (6) This measure does not involve any adjustment of duty rates. Furthermore, it does not involve either the deletion of sub- stances or addition of new substances to Annex 3 to the (1) Regulation (EEC) No 2658/87 established a goods nomen- Combined Nomenclature. clature, hereinafter called the ‘Combined Nomenclature’, to meet, at one and the same time, the requirements of the Common Customs Tariff, the external trade statistics of the Community and other Community policies concerning the (7) The measures provided for in this Regulation are in accor- importation or exportation of goods.
    [Show full text]
  • FIGURE 1 Human Subjects with Bispecific Anti-CD 123 X Anti-CD3 Antibodies
    ( (51) International Patent Classification: SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, A61K 39/395 (2006.01) A61P 35/02 (2006.01) TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. A61P 35/00 (2006.01) C07K 16/28 (2006.01) (84) Designated States (unless otherwise indicated, for every (21) International Application Number: kind of regional protection available) . ARIPO (BW, GH, PCT/US20 19/035203 GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, (22) International Filing Date: TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, 03 June 2019 (03.06.2019) EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, (25) Filing Language: English MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, Cl, CM, GA, GN, GQ, GW, (26) Publication Language: English KM, ML, MR, NE, SN, TD, TG). (30) Priority Data: 62/679,25 1 0 1 June 2018 (01.06.2018) US Published: 62/713,439 0 1 August 2018 (01.08.2018) US — with international search report (Art. 21(3)) — before the expiration of the time limit for amending the (71) Applicant: XENCOR, INC. [US/US]; 111 West Lemon claims and to be republished in the event of receipt of Avenue, Monrovia, CA 91016 (US). amendments (Rule 48.2(h)) (72) Inventors: SAVILLE, Michael, Wayne; d o Xencor, Inc., — with sequence listing part of description (Rule 5.2(a)) I l l West Lemon Avenue, Monrovia, CA 91016 (US).
    [Show full text]
  • Harmonized Tariff Schedule of the United States (2004) -- Supplement 1 Annotated for Statistical Reporting Purposes
    Harmonized Tariff Schedule of the United States (2004) -- Supplement 1 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2004) -- Supplement 1 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. Product CAS No. Product CAS No. ABACAVIR 136470-78-5 ACEXAMIC ACID 57-08-9 ABAFUNGIN 129639-79-8 ACICLOVIR 59277-89-3 ABAMECTIN 65195-55-3 ACIFRAN 72420-38-3 ABANOQUIL 90402-40-7 ACIPIMOX 51037-30-0 ABARELIX 183552-38-7 ACITAZANOLAST 114607-46-4 ABCIXIMAB 143653-53-6 ACITEMATE 101197-99-3 ABECARNIL 111841-85-1 ACITRETIN 55079-83-9 ABIRATERONE 154229-19-3 ACIVICIN 42228-92-2 ABITESARTAN 137882-98-5 ACLANTATE 39633-62-0 ABLUKAST 96566-25-5 ACLARUBICIN 57576-44-0 ABUNIDAZOLE 91017-58-2 ACLATONIUM NAPADISILATE 55077-30-0 ACADESINE 2627-69-2 ACODAZOLE 79152-85-5 ACAMPROSATE 77337-76-9 ACONIAZIDE 13410-86-1 ACAPRAZINE 55485-20-6 ACOXATRINE 748-44-7 ACARBOSE 56180-94-0 ACREOZAST 123548-56-1 ACEBROCHOL 514-50-1 ACRIDOREX 47487-22-9 ACEBURIC ACID 26976-72-7
    [Show full text]