NO20035035D0 - Citrasalt av 5,8,14-triazatetracyklo (10.3.1.0 opphöyet 2,11 .0 opphöyet 4,9) - heksadeca-2. (11), 3,5,7,9-pentaen og farmasöytiskesammensetninger derav - Google Patents

Citrasalt av 5,8,14-triazatetracyklo (10.3.1.0 opphöyet 2,11 .0 opphöyet 4,9) - heksadeca-2. (11), 3,5,7,9-pentaen og farmasöytiskesammensetninger derav

Info

Publication number
NO20035035D0
NO20035035D0 NO20035035A NO20035035A NO20035035D0 NO 20035035 D0 NO20035035 D0 NO 20035035D0 NO 20035035 A NO20035035 A NO 20035035A NO 20035035 A NO20035035 A NO 20035035A NO 20035035 D0 NO20035035 D0 NO 20035035D0
Authority
NO
Norway
Prior art keywords
elevated
triazatetracyclo
citra
hexadeca
penta
Prior art date
Application number
NO20035035A
Other languages
English (en)
Norwegian (no)
Other versions
NO20035035L (no
Inventor
Phillip James Johnson
Peter Robert Rose
Lewin Theophilus Wint
Glenn Robert Williams
Original Assignee
Pfizer Prod 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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=23117854&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=NO20035035(D0) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Pfizer Prod Inc filed Critical Pfizer Prod Inc
Publication of NO20035035L publication Critical patent/NO20035035L/no
Publication of NO20035035D0 publication Critical patent/NO20035035D0/no

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/08—Bridged systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • 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
    • 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
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A61P25/10—Antiepileptics; Anticonvulsants for petit-mal
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • 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
    • A61P25/20—Hypnotics; Sedatives
    • 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
    • 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
    • A61P25/32—Alcohol-abuse
    • 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
    • A61P27/00—Drugs for disorders of the senses
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/02—Antidotes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
    • 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
    • A61P9/06—Antiarrhythmics
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Pain & Pain Management (AREA)
  • Psychiatry (AREA)
  • Addiction (AREA)
  • Cardiology (AREA)
  • Virology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Dermatology (AREA)
  • Diabetes (AREA)
  • Psychology (AREA)
  • Obesity (AREA)
  • AIDS & HIV (AREA)
  • Anesthesiology (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Toxicology (AREA)
  • Hematology (AREA)
  • Molecular Biology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Endocrinology (AREA)
  • Hospice & Palliative Care (AREA)
  • Rheumatology (AREA)
  • Child & Adolescent Psychology (AREA)
NO20035035A 2001-05-14 2003-11-13 Citrasalt av 5,8,14-triazatetracyklo (10.3.1.0 opphöyet 2,11 .0 opphöyet 4,9) - heksadeca-2. (11), 3,5,7,9-pentaen og farmasöytiskesammensetninger derav NO20035035D0 (no)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US29086301P 2001-05-14 2001-05-14
PCT/IB2002/001450 WO2002092597A1 (fr) 2001-05-14 2002-04-26 Sel citrate de 5, 8, 14-triazatetracyclo(10.3.1.0?2,11.04,9¿)-hexadeca-2.(11),3,5,7,9-pentaene

Publications (2)

Publication Number Publication Date
NO20035035L NO20035035L (no) 2003-11-13
NO20035035D0 true NO20035035D0 (no) 2003-11-13

Family

ID=23117854

Family Applications (1)

Application Number Title Priority Date Filing Date
NO20035035A NO20035035D0 (no) 2001-05-14 2003-11-13 Citrasalt av 5,8,14-triazatetracyklo (10.3.1.0 opphöyet 2,11 .0 opphöyet 4,9) - heksadeca-2. (11), 3,5,7,9-pentaen og farmasöytiskesammensetninger derav

Country Status (37)

Country Link
US (1) US6787549B2 (fr)
EP (1) EP1390366B1 (fr)
JP (1) JP4137645B2 (fr)
KR (1) KR20040008175A (fr)
CN (1) CN1509288A (fr)
AP (1) AP1429A (fr)
AR (1) AR035889A1 (fr)
AT (1) ATE303386T1 (fr)
BG (1) BG108344A (fr)
CA (1) CA2446988A1 (fr)
CZ (1) CZ20032917A3 (fr)
DE (1) DE60205888T2 (fr)
DO (1) DOP2002000390A (fr)
DZ (1) DZ3503A1 (fr)
EA (1) EA005529B1 (fr)
EE (1) EE200300557A (fr)
ES (1) ES2245731T3 (fr)
GT (1) GT200200081A (fr)
HR (1) HRP20030911A2 (fr)
HU (1) HUP0304085A3 (fr)
IL (1) IL157874A0 (fr)
IS (1) IS6956A (fr)
MA (1) MA27021A1 (fr)
MX (1) MXPA03010365A (fr)
MY (1) MY134123A (fr)
NO (1) NO20035035D0 (fr)
NZ (1) NZ528209A (fr)
OA (1) OA12600A (fr)
PA (1) PA8545001A1 (fr)
PE (1) PE20021095A1 (fr)
PL (1) PL366774A1 (fr)
SK (1) SK13372003A3 (fr)
TN (1) TNSN03112A1 (fr)
UA (1) UA73421C2 (fr)
UY (1) UY27287A1 (fr)
WO (1) WO2002092597A1 (fr)
ZA (1) ZA200307234B (fr)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PT1044189E (pt) * 1997-12-31 2008-04-22 Pfizer Prod Inc Compostos azapolicíclicos condensados com arilo
MXPA04003807A (es) 2001-11-30 2004-07-30 Pfizer Prod Inc Formulaciones farmaceuticas de 5, 7, 14-trianzatetraciclo [10.3.1.02, 11, 04, 9]-hexadeca -2 (11), 3, 5, 7, 9-pentaeno.
EP1633358A1 (fr) * 2003-05-20 2006-03-15 Pfizer Products Inc. Compositions pharmaceutiques a base de varenicline
US20050043407A1 (en) * 2003-08-22 2005-02-24 Pfizer Inc Pharmaceutical composition for the prevention and treatment of addiction in a mammal
EP2086977A2 (fr) * 2006-11-09 2009-08-12 Pfizer Products Inc. Polymorphes d'intermédiaires nicotiniques
WO2009109651A1 (fr) * 2008-03-06 2009-09-11 Medichem, S.A. Sels d'un dérivé de pyrazino[2,3-h][3]benzazépine
US8039620B2 (en) 2008-05-22 2011-10-18 Teva Pharmaceutical Industries Ltd. Varenicline tosylate, an intermediate in the preparation process of varenicline L-tartrate
US20090318460A1 (en) * 2008-05-26 2009-12-24 Glenmark Amorphous varenicline tartrate and process for the preparation thereof
WO2009155403A2 (fr) * 2008-06-19 2009-12-23 Teva Pharmaceutical Industries Ltd. Processus de préparation de varenicline et d'intermédiaires de ce composé
US20100010221A1 (en) * 2008-07-10 2010-01-14 Revital Lifshitz-Liron Processes for purifying varenicline l-tartrate salt and preparing crystalline forms of varenicline l-tartrate salt
SG171907A1 (en) * 2008-12-11 2011-07-28 S Bio Pte Ltd 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[19.3.1.1(2,6)1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27)j16,21,23-decaene citrate salt
US20100189791A1 (en) 2009-01-23 2010-07-29 Teva Pharmaceutical Industries, Ltd. Delayed release rasagiline malate formulation
WO2010143070A2 (fr) 2009-06-10 2010-12-16 Actavis Group Ptc Ehf Co-précipités amorphes de tartrate de varénicline
US8178537B2 (en) 2009-06-22 2012-05-15 Teva Pharmaceutical Industries Ltd. Solid state forms of varenicline salts and processes for preparation thereof
WO2011140431A1 (fr) 2010-05-06 2011-11-10 Teva Pharmaceutical Industries Ltd. Sels de la varénicline et leurs formes cristallines
JP5925381B2 (ja) 2012-04-13 2016-05-25 ▲連雲▼港金康和信▲薬業▼有限公司Lianyungang Jinkang Hexin Pharmaceutical Co., Ltd. 化合物[4−(2−アミノ−10−メチル−4−オキソ−6,7,8,9−テトラヒドロ−4a,7−エピミノピリミド[4,5−b][1,4]ジアゼピン−5(4H)−イル)ベンゾイル]−グルタメート及びその製造
WO2018154395A2 (fr) 2018-06-11 2018-08-30 Alvogen Malta Operations (Row) Ltd Composition pharmaceutique à libération contrôlée de varénicline
EP3756653A1 (fr) * 2019-06-28 2020-12-30 Alfred E. Tiefenbacher (GmbH & Co. KG) Citrate de varénicline à microparticules
JP2023520164A (ja) * 2020-03-16 2023-05-16 チョンドゥー サイマウント ファーマテック カンパニー リミテッド 5-ht3受容体モジュレーター、結晶形態、それらの製造方法及び使用

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PT1044189E (pt) * 1997-12-31 2008-04-22 Pfizer Prod Inc Compostos azapolicíclicos condensados com arilo
IL137937A0 (en) * 1999-08-27 2001-10-31 Pfizer Prod Inc A pharmaceutical composition for the prevention and treatment of nicotine addiction in a mammal

Also Published As

Publication number Publication date
EE200300557A (et) 2004-04-15
IS6956A (is) 2003-09-15
US20030149091A1 (en) 2003-08-07
DZ3503A1 (fr) 2002-11-21
TNSN03112A1 (fr) 2005-12-23
MY134123A (en) 2007-11-30
NO20035035L (no) 2003-11-13
MA27021A1 (fr) 2004-12-20
ZA200307234B (en) 2004-09-16
PA8545001A1 (es) 2003-09-05
UY27287A1 (es) 2003-02-28
DOP2002000390A (es) 2003-03-15
HUP0304085A3 (en) 2005-09-28
JP4137645B2 (ja) 2008-08-20
HUP0304085A2 (en) 2004-04-28
HRP20030911A2 (en) 2004-02-29
ATE303386T1 (de) 2005-09-15
CA2446988A1 (fr) 2002-11-21
BG108344A (bg) 2004-12-30
WO2002092597A1 (fr) 2002-11-21
AR035889A1 (es) 2004-07-21
DE60205888D1 (de) 2005-10-06
AP2002002522A0 (en) 2002-06-30
AP1429A (en) 2005-06-13
PL366774A1 (en) 2005-02-07
UA73421C2 (en) 2005-07-15
IL157874A0 (en) 2004-03-28
JP2004529186A (ja) 2004-09-24
NZ528209A (en) 2004-09-24
DE60205888T2 (de) 2006-07-06
US6787549B2 (en) 2004-09-07
EA200301120A1 (ru) 2004-02-26
CZ20032917A3 (cs) 2004-07-14
EP1390366B1 (fr) 2005-08-31
EP1390366A1 (fr) 2004-02-25
MXPA03010365A (es) 2004-03-16
KR20040008175A (ko) 2004-01-28
EA005529B1 (ru) 2005-04-28
SK13372003A3 (sk) 2004-08-03
CN1509288A (zh) 2004-06-30
ES2245731T3 (es) 2006-01-16
OA12600A (en) 2006-06-09
GT200200081A (es) 2003-04-22
PE20021095A1 (es) 2002-12-14

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