WO2014113734A3 - Isometheptene isomer - Google Patents

Isometheptene isomer Download PDF

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Publication number
WO2014113734A3
WO2014113734A3 PCT/US2014/012142 US2014012142W WO2014113734A3 WO 2014113734 A3 WO2014113734 A3 WO 2014113734A3 US 2014012142 W US2014012142 W US 2014012142W WO 2014113734 A3 WO2014113734 A3 WO 2014113734A3
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WO
WIPO (PCT)
Prior art keywords
isometheptene
isomer
enantiomer
believed
synthesis
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2014/012142
Other languages
French (fr)
Other versions
WO2014113734A2 (en
Inventor
Seth Lederman
Bruce DAUGHERTY
Leland J. GERSHELL
Darryl Rideout
Andrew Kawasaki
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Tonix Pharmaceuticals Inc
Original Assignee
Tonix Pharmaceuticals Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to KR1020157022165A priority Critical patent/KR20150115809A/en
Priority to JP2015553872A priority patent/JP2016506918A/en
Priority to MX2015009268A priority patent/MX2015009268A/en
Priority to CN201480015557.0A priority patent/CN105722817A/en
Priority to AU2014207347A priority patent/AU2014207347A1/en
Priority to EP14740447.9A priority patent/EP2945928A2/en
Priority to CA2898450A priority patent/CA2898450A1/en
Priority to SG11201505558YA priority patent/SG11201505558YA/en
Application filed by Tonix Pharmaceuticals Inc filed Critical Tonix Pharmaceuticals Inc
Priority to BR112015017176A priority patent/BR112015017176A2/en
Priority to GB1514082.5A priority patent/GB2524706A/en
Publication of WO2014113734A2 publication Critical patent/WO2014113734A2/en
Publication of WO2014113734A3 publication Critical patent/WO2014113734A3/en
Priority to IL239971A priority patent/IL239971A0/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C211/00—Compounds containing amino groups bound to a carbon skeleton
    • C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
    • C07C211/20—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an acyclic unsaturated carbon skeleton
    • C07C211/21—Monoamines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/131—Amines acyclic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A61K31/4152—1,2-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. antipyrine, phenylbutazone, sulfinpyrazone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/60—Salicylic acid; Derivatives thereof
    • A61K31/612—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid
    • A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/06—Antimigraine agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/22—Anxiolytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/36—Opioid-abuse
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B53/00—Asymmetric syntheses
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/235—Saturated compounds containing more than one carboxyl group
    • C07C59/245—Saturated compounds containing more than one carboxyl group containing hydroxy or O-metal groups
    • C07C59/285—Polyhydroxy dicarboxylic acids having five or more carbon atoms, e.g. saccharic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Pain & Pain Management (AREA)
  • Psychiatry (AREA)
  • Immunology (AREA)
  • Addiction (AREA)
  • Transplantation (AREA)
  • Hospice & Palliative Care (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Rheumatology (AREA)
  • Cardiology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

The invention relates to a purified Isometheptene compound comprising the structure according to Formula (I), (Formula (I)) or a hydrochloride, or a pharmaceutically acceptable addition salt thereof. In particular, the disclosure relates to the synthesis, purification and characterization of an Isometheptene isomer mucate crystal 2, wherein the Isometheptene isomer 2 is stereochemically characterized as (R)-enantiomer, respectively. The Isometheptene (R)-enantiomer activity indicates a selective centrally acting selective ligand for Imidazoline subtype 1 (I1) receptor sites; and more specifically, the disclosure provides an antihypertensive composition for treatment of migraine and other neurovascular or neurogenic pain from abdominal distress. (R)-Isometheptene enantiomer or isomer 2 may be an anti-hypertensive agent with lower side effects than the racemate form. Therefore (R)-Isometheptene is believed to be effective against episodic tension-type headaches (ETTH). The (R)-Isometheptene enantiomer or isomer 2 is believed to effectively lower blood pressure, used alone or together with other headache ameliorating drugs. Methods of synthesis and treatment are described. Regarding (R)- Isometheptene crystals data of X-ray crystallography are presented.
PCT/US2014/012142 2013-01-18 2014-01-17 Isometheptene isomer Ceased WO2014113734A2 (en)

Priority Applications (11)

Application Number Priority Date Filing Date Title
CA2898450A CA2898450A1 (en) 2013-01-18 2014-01-17 Isometheptene isomer
MX2015009268A MX2015009268A (en) 2013-01-18 2014-01-17 Isometheptene isomer.
CN201480015557.0A CN105722817A (en) 2013-01-18 2014-01-17 Isometheptene isomer
AU2014207347A AU2014207347A1 (en) 2013-01-18 2014-01-17 Isometheptene isomer
EP14740447.9A EP2945928A2 (en) 2013-01-18 2014-01-17 Isometheptene isomer
SG11201505558YA SG11201505558YA (en) 2013-01-18 2014-01-17 Isometheptene isomer
BR112015017176A BR112015017176A2 (en) 2013-01-18 2014-01-17 isometeptide isomer
KR1020157022165A KR20150115809A (en) 2013-01-18 2014-01-17 Isometheptene isomer
JP2015553872A JP2016506918A (en) 2013-01-18 2014-01-17 Isometeptene isomer
GB1514082.5A GB2524706A (en) 2013-01-18 2014-01-17 Isometheptene isomer
IL239971A IL239971A0 (en) 2013-01-18 2015-07-16 Isometheptene isomer

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
US201361754281P 2013-01-18 2013-01-18
US61/754,281 2013-01-18
US201361793456P 2013-03-15 2013-03-15
US61/793,456 2013-03-15
US201361814664P 2013-04-22 2013-04-22
US61/814,664 2013-04-22
US201461926739P 2014-01-13 2014-01-13
US61/926,739 2014-01-13

Publications (2)

Publication Number Publication Date
WO2014113734A2 WO2014113734A2 (en) 2014-07-24
WO2014113734A3 true WO2014113734A3 (en) 2014-11-27

Family

ID=51210193

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2014/012142 Ceased WO2014113734A2 (en) 2013-01-18 2014-01-17 Isometheptene isomer

Country Status (14)

Country Link
US (1) US9403755B2 (en)
EP (1) EP2945928A2 (en)
JP (1) JP2016506918A (en)
KR (1) KR20150115809A (en)
CN (1) CN105722817A (en)
AU (1) AU2014207347A1 (en)
BR (1) BR112015017176A2 (en)
CA (1) CA2898450A1 (en)
CL (1) CL2015002010A1 (en)
GB (1) GB2524706A (en)
IL (1) IL239971A0 (en)
MX (1) MX2015009268A (en)
SG (1) SG11201505558YA (en)
WO (1) WO2014113734A2 (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015136372A2 (en) 2014-03-14 2015-09-17 Tonix Pharma Holdings Limited Eutectic isometheptene mucate
MX2016013486A (en) * 2014-04-14 2017-05-10 Flex Pharma Inc Ion channel activators and methods of use.
WO2015188005A1 (en) * 2014-06-04 2015-12-10 Seth Lederman Novel (r)-isometheptene compositions and uses
US11253493B2 (en) 2017-01-23 2022-02-22 Cliff-Cartwright Corporation Compositions and methods affecting exercise performance

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1972450A (en) * 1931-07-01 1934-09-04 Bilhuber Inc E Production of derivatives of amino-6-methyl-2-heptene-2
US4522827A (en) * 1982-07-02 1985-06-11 Knoll Ag Method of treating acute pancreatitis with isometheptene
EP0780389A1 (en) * 1995-12-22 1997-06-25 Tobishi Pharmaceutical Co., Ltd. Thiazolidinedione derivatives, process for their preparation and pharmaceutical compositions containing them
KR20000031737A (en) * 1998-11-10 2000-06-05 양주환 Soft capsule formulation containing acetaminophen

Family Cites Families (5)

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Publication number Priority date Publication date Assignee Title
US2230753A (en) 1937-02-15 1941-02-04 Bilhuber Corp E Unsaturated ethylamine derivatives
US7766013B2 (en) * 2001-06-05 2010-08-03 Alexza Pharmaceuticals, Inc. Aerosol generating method and device
WO2002094238A1 (en) * 2001-05-24 2002-11-28 Alexza Molecular Delivery Corporation Delivery of anti-migraine compounds through an inhalation route
WO2010096732A1 (en) * 2009-02-20 2010-08-26 University Of Medicine And Dentistry Of New Jersey Combination therapy to improve drug efficiency
WO2015136372A2 (en) * 2014-03-14 2015-09-17 Tonix Pharma Holdings Limited Eutectic isometheptene mucate

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1972450A (en) * 1931-07-01 1934-09-04 Bilhuber Inc E Production of derivatives of amino-6-methyl-2-heptene-2
US4522827A (en) * 1982-07-02 1985-06-11 Knoll Ag Method of treating acute pancreatitis with isometheptene
EP0780389A1 (en) * 1995-12-22 1997-06-25 Tobishi Pharmaceutical Co., Ltd. Thiazolidinedione derivatives, process for their preparation and pharmaceutical compositions containing them
KR20000031737A (en) * 1998-11-10 2000-06-05 양주환 Soft capsule formulation containing acetaminophen

Non-Patent Citations (11)

* Cited by examiner, † Cited by third party
Title
BLAIR D. JOHNSTON ET AL: "Facile syntheses of the enantiomers of sulcatol", CANADIAN JOURNAL OF CHEMISTRY, vol. 57, no. 2, 15 January 1979 (1979-01-15), pages 233 - 235, XP055180767, ISSN: 0008-4042, DOI: 10.1139/v79-038 *
DANIEL E. JACOME ET AL: "The Non-epileptiform Basilar Artery Migraine", HEADACHE, vol. 26, no. 9, 1 October 1986 (1986-10-01), pages 447 - 450, XP055180679, ISSN: 0017-8748, DOI: 10.1111/j.1526-4610.1986.hed2609447.x *
DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; ELLIS, SYDNEY ET AL: "Effect of amines on blood sugar of the rat", XP002738121, retrieved from STN Database accession no. 1951:24810 *
DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; SAMAAN, KARAM ET AL: "Mode of action of methyloctenylamine hydrochloride (octinum)", XP002738120, retrieved from STN Database accession no. 1937:19086 *
EDWIN WILLEMS ET AL: "Pharmacological profile of the mechanisms involved in the external carotid vascular effects of the antimigraine agent isometheptene in anaesthetised dogs", NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY, vol. 364, no. 1, 1 July 2001 (2001-07-01), pages 27 - 32, XP055180750, ISSN: 0028-1298, DOI: 10.1007/s002100100417 *
ELLIS, SYDNEY ET AL: "Effect of amines on blood sugar of the rat", JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS , 101, 92-100 CODEN: JPETAB; ISSN: 0022-3565, 1951 *
EMMANOUIL LYRIS ET AL.: "Metabolism of isometheptene in human urine and analysis by gas chromatography-mass spectrometry in doping control", J. CHROMATOGR. B, vol. 827, 2005, pages 199 - 204, XP027626950 *
FOTIOS M. PLAKOGIANNIS ET AL.: "Simultaneous GLC Determination of Acetaminophen, Dichloralantipyrine, and Isometheptene Mucate", J. PHARM. SCI., vol. 66, no. 4, 1977, pages 604 - 605, XP055180445 *
GEORGE H. COCOLAS ET AL: "Synthetic Spasmolytic Amines", JOURNAL OF MEDICINAL CHEMISTRY, vol. 8, no. 6, 1 November 1965 (1965-11-01), pages 875 - 877, XP055180779, ISSN: 0022-2623, DOI: 10.1021/jm00330a038 *
SAMAAN, KARAM ET AL: "Mode of action of methyloctenylamine hydrochloride (octinum)", QUARTERLY JOURNAL OF PHARMACY AND PHARMACOLOGY , 9, 647-58 CODEN: QJPPAL; ISSN: 0370-2979, 1936 *
WESLEY G. TAYLOR ET AL.: "Preparation of two metabolites of isometheptene", CAN. J. CHEM., vol. 57, 1979, pages 2103 - 2107, XP055180817 *

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Publication number Publication date
CA2898450A1 (en) 2014-07-24
US20140212486A1 (en) 2014-07-31
US9403755B2 (en) 2016-08-02
SG11201505558YA (en) 2015-08-28
WO2014113734A2 (en) 2014-07-24
EP2945928A2 (en) 2015-11-25
AU2014207347A1 (en) 2015-08-13
BR112015017176A2 (en) 2017-07-11
GB2524706A (en) 2015-09-30
CN105722817A (en) 2016-06-29
GB201514082D0 (en) 2015-09-23
IL239971A0 (en) 2015-08-31
CL2015002010A1 (en) 2016-04-01
AU2014207347A8 (en) 2015-09-03
JP2016506918A (en) 2016-03-07
KR20150115809A (en) 2015-10-14
MX2015009268A (en) 2015-12-07

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