DOCSLIB.ORG

(12) United States Patent (10) Patent No.: US 9,440,908 B2 Himmler 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 9,440,908 B2 Himmler Et Al USOO9440908B2 (12) United States Patent (10) Patent No.: US 9,440,908 B2 Himmler et al. (45) Date of Patent: Sep. 13, 2016 (54) PROCESS FOR PREPARING (58) Field of Classification Search N-(5-CHLORO-2-ISOPROPYLBENZYL) CPC C07C 17/093; CO7C 201/12: C07C 209/00; CYCLOPROPANAMINE C07C 209/26: C07C 209/365; CO7C 209/70; C07C 2101/02: C07C 211/40; C07C 245/20; Monheim (DE) CO7F 3/02 USPC ........................................... 564/384; 570/182 (72) Inventors: Thomas Himmler, Odenthal (DE); See application file for complete search history. Sandra Lehmann, Leverkusen (DE); (56) References Cited Thomas Norbert Muller, Monheim U.S. PATENT DOCUMENTS (DE); Mathias Riedrich, Cologne 6,242,493 B1* 6/2001 Gareau ................. CO7C 311/29 (DE); Lars Rodefeld, Leverkusen (DE); 516.569 Frank Volz, Cologne (DE); Sascha 2012/0065164 A1 3/2012 Bartels ................. CO7D 231/16 514.63 Von Morgenstern, Burscheid (DE) 2013/021791.0 A1* 8, 2013 Lui ....................... CO7C 209/52 560/48 (73) Assignee: BAYER CROPSCIENCE AG (DE) 2014/01484.11 A1 5/2014 Bartels et al. .................. 514.63 (*) Notice: Subject to any disclaimer, the term of this FOREIGN PATENT DOCUMENTS patent is extended or adjusted under 35 U.S.C. 154(b) by 0 days. CN 102421757 A 4/2012 EP 2251331 A1 11 2010 WO WO 2012/059585 A1 5, 2012 (21) Appl. No.: 14/396,570 WO WO 2014,076.007 * 5, 2014 OTHER PUBLICATIONS (22) PCT Filed: Apr. 25, 2013 National Center for Biotechnology Information. PubChem Com pound Database; CID=66158544, https://pubchem.ncbi.nlm.nih. (86). PCT No.: PCT/EP2013/058570 gov/compound 66158544 (accessed Nov. 23, 2015 and first made available online on Oct. 24, 2012—hereafter 544).* S 371 (c)(1), National Center for Biotechnology Information. PubChem Com (2) Date: Oct. 23, 2014 pound Database; CID=67988282, https://pubchem.ncbi.nlm.nih. e a? a 9 gov/compound/67988282 (accessed Nov. 23, 2015 and first made available online on Nov. 30, 2012—hereafter 282).* (87) PCT Pub. No.: WO2013/160387 Overberger (“m-Chlorophenylmethylcarbinol” Organic Syntheses, Coll. vol. 3, p. 200 (1955), vol. 28, p. 28 (1948).* PCT Pub. Date: Oct. 31, 2013 Obushak (“Arenediazonium Tetrachlorocuprates(II). Modified Ver sions of the Meerwein and Sandmeyer Reactions' Russian Journal (65) Prior Publication Data of Organic Chemistry, vol. 38, No. 1, 2002, p. 38-46).* US 2015/0094492 A1 Apr. 2, 2015 yer. The trying some Alkyl-substituted Benzoic Eguchi ("Halogenation Using N-Halogenocompounds. II. Acid (30) Foreign Application Priority Data Catalyzed Bromination of Aromatic Compounds with 1,3-Dibromo 5,5-dimethylhydantoin' The Chemical Society of Japan, Bull. Apr. 26, 2012 (EP) ..................................... 12165663 Chem. Soc. Jpn. 67, 1918-1921, 1994).* U.S. Appl. No. 13/883,241, filed May 2 2013 by Norbert Lui et al., 51) Int. C entitled “Process for the Preparation of Substituted (51) O 21140 2006.O1 N-(Benzyl)Cyclopropanamines by Imine Hydrogenation”. (2006.01) Office Action issued Dec. 10, 2014 in U.S. Appl. No. 13/883,241. CD7C 209/26 (2006.01) International Search Report issued Jul. 29, 2013 in corresponding C07C 17/093 (2006.01) International Application No. PCT/EP2013/058570. H.T. Nagasawa et al. “Latent Inhibitors of Aldehyde Dehydrogenase C. O C: lies, Deterrent Agents”. J. Med. Chem., 27 (10), pp. 1335 CD7C 20/2 (2006.01) Krisztina Vukics et al. “Synthesis of C-Aryl-N- C07C 209/00 (2006.01) Elgory, Synthetic Communications, vol. 33, No. 19, pp. CD7C 209/36 (2006.01) C.G. Overberger et al. “m-Chlorophenylmethylcarbinol”. Organic C07C 209/70 (2006.01) Syntheses, vol. 28, p. 28 (1948). CD7C 245/20 (2006.01) CD7C 249/02 (2006.01) * cited by examiner (52) ".c02 (2006.01) Primary Examiner — Jafar Parsa AV e. we Assistant Examiner — AmV C Bonaparte CPC ........... C07C 211/40 (2013.01); C07C 17/093 (74) Attorney, Agent, or ..., Sink Faber LLP 45/004(2013.01); (2013.01); C07C CO7C 25/06 201/12 (2013.01); (2013.01); C07C (57) ABSTRACT C07C 209/00 (2013.01); C07C 209/26 The present invention relates to a process for preparing (2013.01); C07C 209/365 (2013.01); C07C N-(5-chloro-2-isopropvlbenzVl)cyclopropanaminepropy Zyl)cycloprop by 209/70 (2013.01); C07C 245/20 (2013.01); hydrogenation of N-((5-chloro-2-isopropylphenyl)methyl C07C 249/02 (2013.01); C07F 3/02 (2013.01); enelcyclopropanamine over specific platinum catalysts. C07C 2101/02 (2013.01) 12 Claims, No Drawings US 9,440,908 B2 1. 2 PROCESS FOR PREPARING (Ber. dtsch. Chem. 1927, 1173-1182), aluminium com N-(5-CHLORO-2-ISOPROPYLBENZYL) pounds (J. Chem. Soc. Pak. 1988, 10, 393-395), platinum CYCLOPROPANAMINE catalysts (Chem. Cat. Chem. 2009. 1, 210-221. Synthesis 2003, 11, 1657-1660: additives such as ZnX (X=Cl, Br, I), aluminium(III) chloride, magnesium bromide and copper(I) CROSS-REFERENCE TO RELATED chloride and copper(II) bromide), Raney nickel (Tietze, APPLICATION(S) Eicher in Reaktionen und Synthesen. Thieme Verlag 1981, 466 ff.) and ascorbic acid (Commun. Fac. Sci. Univ. Ank. The present application is a 35 U.S.C. S371 national phase Serie B 1988, 34, 159-162). In addition, it is known in the conversion of PCT/EP2013/058570 filed on Apr. 25, 2013, literature that aromatic nitro compounds can be reduced by which claims priority of European Application No. 10 means of complex borohydrides such as Sodium borohy 12165663.1 filed on Apr. 26, 2012. Applicants claim priority dride, Sodium cyanoborohydride, Sodium acetoxyborohy to each of the foregoing applications. The PCT International dride and also aluminates Such as lithium aluminium hydride Application was published in the English language. or diisobutylaluminium hydride. Appropriate reaction con The present invention relates to a process for preparing ditions are known per se to those skilled in the art. N-(5-chloro-2-isopropylbenzyl)cyclopropanamine by 15 Preparative processes for the chlorination of aromatics by hydrogenation of N-(5-chloro-2-isopropylphenyl)methyl means of the Sandmeyer reaction are described in the enelcyclopropanamine over specific platinum catalysts. literature (e.g. Organikum 22nd edition, Wiley-VCH, 640 Preparative processes for brominating strongly deacti ff.). The diazotization of 3-bromo-4-isopropylaniline is vated aromatics such as p-alkyl-substituted nitrobenzenes or described in J. Org. Chem. 1963, 28, 1917-1919 and J. nitrobenzene itself are described in the literature. The bro Chem. Soc. 1952, 4443 ff. mination of p-nitroethylbenzene by means of iron and The conversion of a bromoaromatic into the correspond bromine has been described with very low yields (55% yield ing Grignard compound (J. Org. Chem. 1963. 28, 1917 of crude product and 34% after distillation) and with long 1919) and the reaction of this with dimethylformamide to reaction times of over 24 hours (J. Am. Chem. Soc. 1950, 72, form benzaldehyde (Synth. Commun. 1984, 228-230) has 2804). The bromination of nitrobenzene by means of iron 25 been described. The reaction of m-bromochlorobenzene and bromine is described with a yield of always 60-75% of with magnesium, with selective insertion of the magnesium isolated compound (cf. Organic Synthesis 1941, Coll. Vol. 1, into the C Br bond, and the subsequent reaction with an 123, ibid. 1928, Vol. 8, 48). A further possible way of electrophile (acetaldehyde) is likewise known (Org. Synth. brominating deactivated aromatics by means of potassium 1955, Coll. Vol. 3, 200; ibid. 1948, Vol. 28, 28). bromate is known (J. Org. Chem. 1981, 46, 2169-217 1). The reductive amination of benzaldehydes by means of However, reactions are problematical from a safety point of 30 cyclopropylamine is described in PCT/EP2011/069426. view because of the decomposition of potassium bromate in Under the conditions described there, the selective hydro over 70% strength sulphuric acid solution. Furthermore, the genation without opening of the cyclopropane ring is pos bromination of p-nitrotoluene or nitrobenzene by means of sible. However, dehalogenation of the corresponding chlo N-bromosuccinimide in half-concentrated sulphuric acid is roaromatics cf. formula (II) occurs as undesirable known (Org. Lett. 2006, 8, 645-647, J. Org. Chem. 1965, 30, 35 secondary reaction under the hydrogenation conditions. Fur 304-306). However, this reaction requires N-bromosuccin thermore, it is possible to employ a Leukart-Wallach reac imide as brominating reagent. Dimethyldibromohydantoin tion for carrying out the reductive amination (imine reduc is found to be significantly more efficient (cf. Bull. Chem. tion by means of formic acid and derivatives, cf. J. Am. Soc. Jpn. 1994, 67, 1918-1921). However, trifluorometh Chem. Soc. 1936,58, 1808-1811, ibid. 1950, 72,3073-3075. anesulphonic acid, a very expensive reagent, is used here as 40 Bull. Chem. Soc. Jap. 1976, 49, 2485-2490). proton Source, which would make an industrial process Proceeding from this prior art, it is an object of the present uneconomical. The use of Sulphuric acid as proton Source is invention to provide an alternative process for preparing also described in the same reference. However, dichlo N-(5-chloro-2-isopropylbenzyl)cyclopropanamine in high romethane, which is a problematical solvent from both an purity, yield and better quality without opening of the environmental and process engineering point of view, is cyclopropane ring and with simultaneous Suppression of the used as solvent and, in addition, a maximum yield in the 45 secondary dehalogenation reaction, with the process prefer bromination of p-nitrotoluene of 84% is achieved. Dibro ably being simple and inexpensive to carry out. In particular, moisocyanuric acid is also known as brominating reagent for the process sought should make it possible to obtain the deactivated aromatics (Organikum, 22nd edition, Wiley desired target compound without the necessity of a complex VCH, pp. 367–368.) purification. In addition, it is known that p-nitrocumene can be con 50 This object is achieved by a novel process for preparing verted into bromonitrocumene using a substoichiometric N-(5-chloro-2-isopropylbenzyl)cyclopropanamine.
Load more

Recommended publications
  • Lonsurf (Trifluridine/Tipiracil) Were Bone Marrow Suppression and Gastrointestinal Toxicity
    PRODUCT MONOGRAPH INCLUDING PATIENT MEDICATION INFORMATION PrLONSURF® trifluridine and tipiracil tablet 15 mg trifluridine/ 6.14 mg tipiracil (as tipiracil hydrochloride) 20 mg trifluridine / 8.19 mg tipiracil (as tipiracil hydrochloride) Antineoplastic Agent Thymidine phosphorylase inhibitor/nucleoside metabolic inhibitor Taiho Pharma Canada, Inc. Date of Initial Approval: 2010 Winston Park Drive, Suite 503 January 23, 2018 Oakville, Ontario L6H 5R7 Canada Submission Control No: 205852 Page 1 of 35 RECENT MAJOR LABEL CHANGES Not Applicable TABLE OF CONTENTS RECENT MAJOR LABEL CHANGES ......................................................................................2 TABLE OF CONTENTS ..............................................................................................................2 PART I: HEALTH PROFESSIONAL INFORMATION ............................................................4 1 INDICATIONS....................................................................................................................4 1.1 Pediatrics ....................................................................................................................4 1.2 Geriatrics ....................................................................................................................4 2 CONTRAINDICATIONS ..................................................................................................4 3 DOSAGE AND ADMINISTRATION ...............................................................................4 3.1 Dosing Considerations
    [Show full text]
  • These Highlights Do Not Include All the Information Needed to Use LONSURF Safely and Effectively
    LONSURF- trifluridine and tipiracil tablet, film coated Taiho Pharmaceutical Co., Ltd. ---------- HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use LONSURF safely and effectively. See full prescribing information for LONSURF. LONSURF (trifluridine and tipiracil) tablets, for oral use Initial U.S. Approval: 2015 RECENT MAJOR CHANGES Indications and Usage (1.2) 2/2019 Recommended Dosage (2.1) 2/2019 Warnings and Precaution (5.1) 2/2019 INDICATIONS AND USAGE LONSURF is a combination of trifluridine, a nucleoside metabolic inhibitor, and tipiracil, a thymidine phosphorylase inhibitor, indicated for the treatment of adult patients with: metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy. (1.1) metastatic gastric or gastroesophageal junction adenocarcinoma previously treated with at least two prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu- targeted therapy. (1.2) DOSAGE AND ADMINISTRATION Recommended Dosage: 35 mg/m2/dose orally twice daily with food on Days 1 through 5 and Days 8 through 12 of each 28-day cycle. (2.1) DOSAGE FORMS AND STRENGTHS Tablets: 15 mg trifluridine/6.14 mg tipiracil (3) 20 mg trifluridine/8.19 mg tipiracil (3) CONTRAINDICATIONS None. (4) WARNINGS AND PRECAUTIONS Severe Myelosuppression: Obtain complete blood counts prior to and on Day 15 of each cycle. Withhold and resume at next lower LONSURF dosage as recommended. (2.1, 5.1) Embryo-Fetal Toxicity: Can cause fetal harm.
    [Show full text]
  • Aqueous Immiscible Layered Double Hydroxides – AIM-Ldhs Kanittika Ruengkajorn, Christopher M
    Electronic Supplementary Material (ESI) for Materials Chemistry Frontiers. This journal is © the Partner Organisations 2018 Aqueous Immiscible Layered Double Hydroxides – AIM-LDHs Kanittika Ruengkajorn, Christopher M. R. Wright. Nicholas H. Rees, Jean-Charles Buffet and Dermot O’Hare* Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, OX3 1TA, Oxford. E-mail: [email protected] Table of contents 1. General experimental details S2 1.1. Analytical techniques for LDH characterisation S2 1.2. Synthesis of Conventional, AMO- and AIM-LDHs S4 2. Supplementary experimental data S6 2.1 Figures S6 2.2 Tables S36 3 References S47 S1 1. General experimental details 1.1 Analytical techniques for LDH characterisation 1.1.1. X-ray powder diffraction (XRD) X-ray powder diffraction (XRD) results were investigated by using a PANalytical X’Pert Pro diffractometer in reflection mode operating at a voltage of 40 kV and a current intensity of 40 mA with Cu-Kα radiation (λ = 1.5406 Å). LDHs and LDOs powder were placed into stainless steel sample holders. A 1° slit was used. Bragg reflections due to sample holder were observed at 2θ = 43-44° and 50° and from silicon wafer were located at 2θ = 33°, 62° and 69°. The Scherrer’s equation was used to estimate the mean crystallite domain length (CDL) of the LDHs; CDL = Kλ(βcosθ)-1, where CDL = the mean crystallite domain length, K = Scherrer constant, λ = the wavelength of the radiation, and β = the full-width at half-maximum height (FWHM) values of a reflection located at 2θ. Thus, the CDL along c- axis (CDL003) can be calculated from the full-width at half-maximum height values of the (003) Bragg reflection, which is assumed to be the total crystal thickness along the c-axis.
    [Show full text]
  • Justification Document for the Selection of a Corap Substance
    JUSTIFICATION DOCUMENT FOR THE SELECTION OF A CORAP SUBSTANCE ________________________________________________________________ Justification Document for the Selection of a CoRAP Substance Substance Name (public name): Diethyl Ether EC Number: 200-467-2 CAS Number: 60-29-7 Authority: France Date: 21/03/2017 Cover Note This document has been prepared by the evaluating Member State given in the CoRAP update. JUSTIFICATION DOCUMENT FOR THE SELECTION OF A CORAP SUBSTANCE _______________________________________________________________ Table of Contents 1 IDENTITY OF THE SUBSTANCE 3 1.1 Other identifiers of the substance 3 2 OVERVIEW OF OTHER PROCESSES / EU LEGISLATION 5 3 HAZARD INFORMATION (INCLUDING CLASSIFICATION) 7 3.1 Classification 7 3.1.1 Harmonised Classification in Annex VI of the CLP 7 3.1.2 Self classification 7 3.1.3 Proposal for Harmonised Classification in Annex VI of the CLP 7 4 INFORMATION ON (AGGREGATED) TONNAGE AND USES 8 4.1 Tonnage and registration status 8 4.2 Overview of uses 8 5. JUSTIFICATION FOR THE SELECTION OF THE CANDIDATE CORAP SUBSTANCE 10 5.1. Legal basis for the proposal 10 5.2. Selection criteria met (why the substance qualifies for being in CoRAP) 10 5.3 Initial grounds for concern to be clarified under Substance Evaluation 10 5.4 Preliminary indication of information that may need to be requested to clarify the concern 11 5.5 Potential follow-up and link to risk management 11 EC no 200-467-2 MSCA - France Page 2 of 11 JUSTIFICATION DOCUMENT FOR THE SELECTION OF A CORAP SUBSTANCE _______________________________________________________________
    [Show full text]
  • GRAS Notice 695, Dimethyl Ether
    GRAS Notice (GRN) No. 695 http://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/default.htm Callaghan Sl ~ TECHNOLOGY..,u CESS March 17, 2017 Dr. Paulette Gaynor Office of Food Additive Safety (FHS-200) MAR 2 0 2017 Center for Food Safety and Applied Nutrition Food and Drug Administration OFFICE OF FOOD ADDITIVE SAFETY 5100 Campus Drive College Park, MD 20740 Re: GRAS Notice for Dimethyl Ether Dear Dr. Gaynor In accordance with 21 CFR §170 Subpart E consisting of §170.203 through 170.285, Callaghan Innovation hereby informs the United States Food and Drug Administration of the conclusion that the intended use of dimethyl ether as an extraction solvent in the processing of various food products is Generally Recognized as Safe (GRAS) as described in the enclosed notice, and thereby the intended use of dimethyl ether is not subject to the premarket approval requirements of the Federal Food, Drug, and Cosmetic Act. I hereby certify that the enclosed electronic files were scanned for viruses prior to submission and are thus certified as being virus-free using McAfee VirusScan 8.8. Should you have any questions or concerns regarding this GRAS Notice, please do not hesitate to contact me at any point during the review process so that we may provide a response in a timely manner. Yours sincerely (b) (6) Stephen Tallon, Ph.D. Senior Research Engineer Callaghan Innovation GRAS Notice for the Use of Dimethyl Ether as an Extraction Solvent Prepared for: Office of Food Additive Safety (FHS-200) Center for Food Safety and Applied Nutrition Food and Drug Administration 5100 Campus Drive College Park, MD 20740 Submitted by: Callaghan Innovation 69 Gracefield Road Lower Hutt 5040 New Zealand March 7, 2017 GRAS Notice for the Use of Dimethyl Ether as an Extraction Solvent Table of Contents Page Part 1.
    [Show full text]
  • [Product Monograph Template
    PRODUCT MONOGRAPH INCLUDING PATIENT MEDICATION INFORMATION PrLONSURF® trifluridine and tipiracil tablet 15 mg trifluridine/ 6.14 mg tipiracil (as tipiracil hydrochloride) 20 mg trifluridine / 8.19 mg tipiracil (as tipiracil hydrochloride) Antineoplastic Agent Thymidine phosphorylase inhibitor/nucleoside metabolic inhibitor Taiho Pharma Canada, Inc. Date of Initial Approval: 2010 Winston Park Drive, Suite 503 January 23, 2018 Oakville, Ontario L6H 5R7 Date of Revision: Canada November 18, 2019 Submission Control No: 227070 Page 1 of 40 RECENT MAJOR LABEL CHANGES INDICATIONS (1) 11-2019 WARNINGS AND PRECAUTIONS (6), Geriatrics (6.1.4) 11-2019 TABLE OF CONTENTS RECENT MAJOR LABEL CHANGES ........................................................................... 2 TABLE OF CONTENTS ................................................................................................. 2 PART I: HEALTH PROFESSIONAL INFORMATION ................................................... 4 1 INDICATIONS ..................................................................................................... 4 1.1 Pediatrics .................................................................................................... 4 1.2 Geriatrics .................................................................................................... 4 2 CONTRAINDICATIONS ...................................................................................... 4 3 DOSAGE AND ADMINISTRATION .................................................................... 4 3.1 Dosing Considerations...............................................................................
    [Show full text]
  • Auspar Attachment 1: Product Information: Trifluridine/Tipiracil
    Attachment 1: Product information for AusPAR Lonsurf and Orcantas Servier Laboratories Australia Pty Ltd PM-2016-00929-1-4 Final 12 June 2018. This Product Information was approved at the time this AusPAR was published. LONSURF (trifluridine/tipiracil) – Product Information 1 (20) Product Information NAME OF THE MEDICINE LONSURF 15/6.14 Trifluridine 15 mg/ tipiracil hydrochloride 7.065 mg (equivalent to tipiracil 6.14 mg) LONSURF 20/8.19 Trifluridine 20 mg/ tipiracil hydrochloride 9.420 mg (equivalent to tipiracil 8.19 mg) The active components of LONSURF are trifluridine and tipiracil hydrochloride. Trifluridine Trifluridine has the chemical name 2′-deoxy-5-(trifluoromethyl)uridine Chemical structure: Molecular formula: C10H11F3N2O5 (Relative Molecular Mass: 296.20) CAS Registry Number: 70-00-8 Tipiracil hydrochloride Tipiracil hydrochloride has the chemical name 5-chloro-6-[(2-iminopyrrolidin-1-yl)methyl]pyrimidine- 2,4-(1H,3H)-dione monohydrochloride. Chemical structure: Molecular formula: C9H11ClN4O2•HCl (Relative Molecular Mass: 279.12) CAS Registry Number: 183204-72-0 DESCRIPTION Trifluridine is a white crystalline powder, soluble in water, ethanol, 0.01 mol/L hydrochloric acid, 0.01 mol/L sodium hydroxide solution; freely soluble in methanol, acetone; sparingly soluble in 2- propanol, acetonitrile; slightly soluble in diethyl ether; and very slightly soluble in isopropyl ether. Tipiracil hydrochloride is a white crystalline powder, soluble in water, 0.01 mol/L hydrochloric acid, and 0.01 mol/L sodium hydroxide; slightly soluble in methanol; very slightly soluble in ethanol; and practically insoluble in acetonitrile, 2-propanol, acetone, diisopropyl ether, and diethyl ether. Version 1 Attachment 1: Product information for AusPAR Lonsurf and Orcantas Servier Laboratories Australia Pty Ltd PM-2016-00929-1-4 Final 12 June 2018.
    [Show full text]
  • Product Monograph
    PRODUCT MONOGRAPH INCLUDING PATIENT MEDICATION INFORMATION PrLONSURF® trifluridine and tipiracil tablet 15 mg trifluridine/ 6.14 mg tipiracil (as tipiracil hydrochloride) 20 mg trifluridine / 8.19 mg tipiracil (as tipiracil hydrochloride) Antineoplastic Agent Thymidine phosphorylase inhibitor/nucleoside metabolic inhibitor Taiho Pharma Canada, Inc. Date of Initial Approval: 2010 Winston Park Drive, Suite 503 JAN 23, 2018 Oakville, Ontario L6H 5R7 Date of Revision: Canada OCT 29, 2020 Submission Control No: 235999 Page 1 of 37 RECENT MAJOR LABEL CHANGES INDICATIONS (1) 11-2019 WARNINGS AND PRECAUTIONS (6), Geriatrics (6.1.4) 11-2019 DOSAGE AND ADMINISTRATION (3.3) 10-2020 WARNINGS AND PRECAUTIONS (6), Renal 10-2020 TABLE OF CONTENTS RECENT MAJOR LABEL CHANGES ........................................................................... 2 TABLE OF CONTENTS ................................................................................................. 2 PART I: HEALTH PROFESSIONAL INFORMATION ................................................... 4 1 INDICATIONS ..................................................................................................... 4 1.1 Pediatrics .................................................................................................... 4 1.2 Geriatrics .................................................................................................... 4 2 CONTRAINDICATIONS ...................................................................................... 4 3 DOSAGE AND ADMINISTRATION ...................................................................
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8.445,002 B2 Mansouri (45) Date of Patent: May 21, 2013
    USOO8445002B2 (12) United States Patent (10) Patent No.: US 8.445,002 B2 Mansouri (45) Date of Patent: May 21, 2013 (54) DERMAL DELIVERY COMPOSITIONS (56) References Cited COMPRISING ACTIVE AGENT-CALCUM PHOSPHATE PARTICLE COMPLEXES AND U.S. PATENT DOCUMENTS METHODS OF USING THE SAME 4,948,575 A * 8/1990 Cole et al. ....................... 424/44 5,158,756 A * 10/1992 Ogawa et al. ...... ... 423.309 (75) Inventor: Zahra Mansouri, Tahoe City, CA (US) 5,604.200 A * 2/1997 Taylor-McCord ............. 514/9.3 6,096,324 A 8, 2000 Mansouri 6,120,782 A 9, 2000 Mansouri (73) Assignee: Laboratory Skin Care, Inc., Tahoe 6,262,020 B1* T/2001 Lezdey et al. .................. 514/5.9 City, CA (US) 6,395,311 B2* 5/2002 Jia .................. ... 424/744 6,573.249 B2 * 6/2003 Lezdey et al. ................... 514/54 (*) Notice: Subject to any disclaimer, the term of this 2002fOO18797 A1 2/2002 Cui et al. patent is extended or adjusted under 35 2005/00 13874 A1 1/2005 Ito et al. ........................ 424,602 2005/02341 14 A1 10, 2005 Lee U.S.C. 154(b) by 0 days. 2006/0257658 A1* 11/2006 Tanaka et al. ................. 428/402 2007, OOO3487 A1* 1/2007 Ek ............... ... 424/46 (21) Appl. No.: 12/742,235 2008/005.1335 A1 2/2008 Kleiner et al. .................. 514/12 2008, 0220233 A1 9/2008 Kjellin et al. (22) PCT Filed: May 6, 2010 2010/0086606 A1* 4/2010 Ogawa .......................... 424/489 2012/0130435 A1* 5, 2012 Hart et al. ...... ... 606,301 (86). PCT No.: PCT/US2O10/033942 2012/0134919 A1* 5/2012 Engqvist et al.
    [Show full text]
  • Targets in Heterocyclic Systems
    Italian Society of Chemistry Division of Organic Chemistry Division of Medicinal Chemistry Division of Mass Spectrometry TARGETS IN HETEROCYCLIC SYSTEMS Chemistry and Properties Volume 17 (2013) Reviews and Accounts on Heterocyclic Chemistry http://www.soc.chim.it/it/libriecollane/target_hs Editors Prof. Orazio A. Attanasi University of Urbino “Carlo Bo”, Urbino, Italy and Prof. Domenico Spinelli University of Bologna, Bologna, Italy Published by: Società Chimica Italiana Viale Liegi, 48 00198 Roma Italy ___________________________________________________________________________ Copyright © 2013 Società Chimica Italiana All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means (electronic, electrostatic, magnetic tape, mechanical, photocopying, recording or otherwise) without permission in writing from the publishers. A person may photocopy an article for personal use. Volume 1 (1997) First edition 1997 ISBN 88-86208-24-3 Second edition 1999 ISBN 88-86208-24-3 Volume 2 (1998) First edition 1999 ISBN 88-86208-11-1 Volume 3 (1999) First edition 2000 ISBN 88-86208-13-8 Volume 4 (2000) First edition 2001 ISBN 88-86208-16-2 Volume 5 (2001) First edition 2002 ISBN 88-86208-19-7 Volume 6 (2002) First edition 2003 ISBN 88-86208-23-5 Volume 7 (2003) First edition 2004 ISBN 88-86208-28-6 ISSN 1724-9449 Volume 8 (2004) First edition 2005 ISBN 88 86208-29-4 ISSN 1724-9449 Volume 9 (2005) First edition 2006 ISBN 88 86208-31-6 ISSN 1724-9449 Volume 10 (2006) First edition
    [Show full text]
  • WO 2019/002407 Al 03 January 2019 (03.01.2019) W !P O PCT
    (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 2019/002407 Al 03 January 2019 (03.01.2019) W !P O PCT (51) International Patent Classification: Near Gangotri Circle, Nikol, Ahmedabad Gujarat 382350 C07D 403/06 (2006.01) A61K 31/513 (2006.01) (IN). SAVALIYA, Bhavesh Laljibhai; At: Itali, Men- A61P 35/00 (2006.01) darda, Junagadh Gujarat 362260 (IN). KOILPILLAI, Joseph Prabahar; H-56, TNHB Phase-II, Perumalpu- (21) International Application Number: ram, Tirunelveli, Tamil Nadu 627007 (IN). AGARW- PCT/EP20 18/067322 AL, Virendra Kumar; A14, Vishal residency, Anandna- (22) International Filing Date: gar charrasta, Satellite, Ahmedabad Gujarat 380015 (IN). 27 June 2018 (27.06.2018) CHAVAN, Rahul Baburao; 525, Manisha Nivas, Nanded road, Ahmedpur, Maharashtra 4135 15 (IN). ARABIANI, (25) Filing Language: English Mohsin Razakbhai; 32A Gulzar Park Gate No. 1, Opp. Es- (26) Publication Language: English sar Petrol Pump, Sarkhej Juhapura Road, Ahmedabad Gu jarat 380055 (IN). HEDAPARA, Kalpesh Ratilal; B-205, (30) Priority Data: Shreenidhi apartment, Haridarshan road, Ahmedabad Gu 201721022621 28 June 2017 (28.06.2017) jarat 382350 (IN). KATARIYA, Lalit Keshav; D-102, 201721022621 26 June 2018 (26.06.2018) Garden Residency 2, Behind Shyam villa, Ahmedabad Gu (71) Applicant: AMNEAL PHARMACEUTICALS COM¬ jarat 380058 (IN). PATEL, Vijay Premajibhai; A-20, PANY GMBH [CH/CH]; Turmstrasse 30, 63 12 Stein- Shivalik society, Patel street, Bayad Gujarat 383335 (IN). hausen (CH). THUMMAR, Mahesh Kurajibhai; L-204, Nilkanth or chid, Sterling city, Bopal, Ahmedabad Gujarat 380058 (IN). (72) Inventors: MAHETA, Abhay Subodhbhai; F-302, Bi- BHALODIYA, Rahul Harsukhlal; 1-504, Prathna lavish, nori sonnet, , Near Govt.
    [Show full text]
  • Peroxide Forming Chemicals to Counter Peroxide Formation
    Peroxide-Forming Chemicals Overview Peroxide-forming chemicals are a class of compounds that have the ability to form shock-sensitive explosive peroxide crystals. Many of the organic solvents commonly used in laboratories have the potential to form explosive peroxide crystals. Diethyl ether and tetrahydrofuran are two of the more common peroxide- forming chemicals used today. Therefore, it is extremely important that this procedure be followed regarding the identification, handling, storage, and disposal of peroxide-forming chemicals. Peroxide Formation Under normal storage conditions the materials listed in this document have the potential to generate and accumulate peroxide crystal formations, which may violently detonate when subjected to thermal or mechanical shock. Peroxide-forming chemicals react with oxygen – even at low concentrations – to form peroxy compounds. The risk associated with peroxide formation increases if the peroxide crystallizes or becomes concentrated by evaporation or distillation. Factors that affect rate of peroxide formation include exposure to air, light and heat, moisture, and contamination from metals. Manufacturers may add an inhibitor to peroxide forming chemicals to counter peroxide formation. For many peroxide-forming solvents, butylated hydroxy toluene (BHT) is commonly added. BHT ‘scavenges’ oxygen in the solvent and prevents it from reacting with the solvent to form peroxides. Over time, BHT or other inhibitor in the solvent can become exhausted allowing peroxides to form. Distilling the solvent can completely remove the BHT and make the solvent immediately susceptible to peroxide formation. Peroxide crystals may form on the container plug or the threads of the lid and detonate when the lid is twisted. Do not open a liquid organic peroxide or peroxide-forming chemical if crystals or a precipitate are present.
    [Show full text]