SK287150B6 - Benzoxazepínové deriváty, farmaceutický prostriedok s ich obsahom a ich použitie - Google Patents

Benzoxazepínové deriváty, farmaceutický prostriedok s ich obsahom a ich použitie Download PDF

Info

Publication number: SK287150B6
Authority: SK; Slovakia
Prior art keywords: alkyl; formula; pyrrolo; tetrahydro; benzoxazepin
Prior art date: 2001-06-11

Application number

SK1518-2003A

Other languages

English (en)

Slovak (sk)

Other versions

SK15182003A3 (sk

Inventor

Simon James Anthony Grove

Mingqiang Zhang

Mohammad Shahid

Original Assignee

N.V. Organon

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.)

2001-06-11

Filing date

2002-06-05

Publication date

2010-01-07

2002-06-05 Application filed by N.V. Organon filed Critical N.V. Organon

2004-05-04 Publication of SK15182003A3 publication Critical patent/SK15182003A3/sk

2010-01-07 Publication of SK287150B6 publication Critical patent/SK287150B6/sk

Links

ZCXLTWVZYXBHJS-UHFFFAOYSA-N 1,2-benzoxazepine Chemical class O1N=CC=CC2=CC=CC=C12 ZCXLTWVZYXBHJS-UHFFFAOYSA-N 0.000 title claims abstract description 26
239000000774 AMPA receptor agonist Substances 0.000 title description 2
125000001424 substituent group Chemical group 0.000 claims abstract description 23
125000003545 alkoxy group Chemical group 0.000 claims abstract description 20
102000003678 AMPA Receptors Human genes 0.000 claims abstract description 17
108090000078 AMPA Receptors Proteins 0.000 claims abstract description 17
229910052736 halogen Inorganic materials 0.000 claims abstract description 15
150000002367 halogens Chemical class 0.000 claims abstract description 15
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 10
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 10
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 9
208000012902 Nervous system disease Diseases 0.000 claims abstract description 7
208000025966 Neurological disease Diseases 0.000 claims abstract description 7
125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 7
208000020016 psychiatric disease Diseases 0.000 claims abstract description 7
150000003839 salts Chemical class 0.000 claims abstract description 7
229910052760 oxygen Inorganic materials 0.000 claims abstract description 6
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
210000003169 central nervous system Anatomy 0.000 claims abstract description 5
125000005842 heteroatom Chemical group 0.000 claims abstract description 5
230000001404 mediated effect Effects 0.000 claims abstract description 5
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 5
125000004043 oxo group Chemical group O=* 0.000 claims abstract description 5
125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 5
229910052717 sulfur Inorganic materials 0.000 claims abstract description 5
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 4
230000009782 synaptic response Effects 0.000 claims abstract description 3
150000001875 compounds Chemical class 0.000 claims description 108
DIKHYVVASLIVKI-UHFFFAOYSA-N 2h-1,4-benzoxazepin-5-one Chemical compound O=C1N=CCOC2=CC=CC=C12 DIKHYVVASLIVKI-UHFFFAOYSA-N 0.000 claims description 75
125000000217 alkyl group Chemical group 0.000 claims description 30
239000003814 drug Substances 0.000 claims description 14
229940079593 drug Drugs 0.000 claims description 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
208000035475 disorder Diseases 0.000 claims description 6
230000015654 memory Effects 0.000 claims description 5
208000024827 Alzheimer disease Diseases 0.000 claims description 3
230000032683 aging Effects 0.000 claims description 3
201000010099 disease Diseases 0.000 claims description 3
201000000980 schizophrenia Diseases 0.000 claims description 3
206010001605 Alcohol poisoning Diseases 0.000 claims description 2
208000019901 Anxiety disease Diseases 0.000 claims description 2
206010003805 Autism Diseases 0.000 claims description 2
208000020706 Autistic disease Diseases 0.000 claims description 2
208000020358 Learning disease Diseases 0.000 claims description 2
208000026139 Memory disease Diseases 0.000 claims description 2
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201000001880 Sexual dysfunction Diseases 0.000 claims description 2
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230000003920 cognitive function Effects 0.000 claims description 2
206010015037 epilepsy Diseases 0.000 claims description 2
208000014674 injury Diseases 0.000 claims description 2
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238000004519 manufacturing process Methods 0.000 claims description 2
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208000015122 neurodegenerative disease Diseases 0.000 claims description 2
231100000872 sexual dysfunction Toxicity 0.000 claims description 2
201000006152 substance dependence Diseases 0.000 claims description 2
208000011117 substance-related disease Diseases 0.000 claims description 2
230000008733 trauma Effects 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims 1
238000002560 therapeutic procedure Methods 0.000 claims 1
125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 7
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 144
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 79
239000000243 solution Substances 0.000 description 70
238000002451 electron ionisation mass spectrometry Methods 0.000 description 58
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 51
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239000000203 mixture Substances 0.000 description 45
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 40
239000002904 solvent Substances 0.000 description 37
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
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VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 26
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
239000000047 product Substances 0.000 description 22
239000012044 organic layer Substances 0.000 description 21
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
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239000002253 acid Substances 0.000 description 16
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238000000034 method Methods 0.000 description 13
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239000012299 nitrogen atmosphere Substances 0.000 description 10
238000002360 preparation method Methods 0.000 description 10
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
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PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 9
150000001732 carboxylic acid derivatives Chemical class 0.000 description 9
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CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 8
229910000024 caesium carbonate Inorganic materials 0.000 description 8
238000003818 flash chromatography Methods 0.000 description 8
239000001257 hydrogen Substances 0.000 description 8
229910052739 hydrogen Inorganic materials 0.000 description 8
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
230000004913 activation Effects 0.000 description 7
238000006243 chemical reaction Methods 0.000 description 7
239000010410 layer Substances 0.000 description 7
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
239000004480 active ingredient Substances 0.000 description 6
150000001408 amides Chemical group 0.000 description 6
150000001412 amines Chemical class 0.000 description 6
239000000460 chlorine Substances 0.000 description 6
238000001704 evaporation Methods 0.000 description 6
230000008020 evaporation Effects 0.000 description 6
239000012312 sodium hydride Substances 0.000 description 6
229910000104 sodium hydride Inorganic materials 0.000 description 6
238000012360 testing method Methods 0.000 description 6
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
239000002585 base Substances 0.000 description 5
210000004556 brain Anatomy 0.000 description 5
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PRAYXGYYVXRDDW-UHFFFAOYSA-N piperidin-2-ylmethanol Chemical compound OCC1CCCCN1 PRAYXGYYVXRDDW-UHFFFAOYSA-N 0.000 description 5
125000006239 protecting group Chemical group 0.000 description 5
230000004044 response Effects 0.000 description 5
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 5
LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 4
ATCRIUVQKHMXSH-UHFFFAOYSA-N 2,4-dichlorobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1Cl ATCRIUVQKHMXSH-UHFFFAOYSA-N 0.000 description 4
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
RAAGZOYMEQDCTD-UHFFFAOYSA-N 2-fluorobenzoyl chloride Chemical compound FC1=CC=CC=C1C(Cl)=O RAAGZOYMEQDCTD-UHFFFAOYSA-N 0.000 description 4
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
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Classifications

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- C07D515/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D515/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D515/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
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- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- 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
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- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
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Landscapes

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Organic Chemistry (AREA)
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Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
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Animal Behavior & Ethology (AREA)
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Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Plural Heterocyclic Compounds (AREA)

SK1518-2003A 2001-06-11 2002-06-05 Benzoxazepínové deriváty, farmaceutický prostriedok s ich obsahom a ich použitie SK287150B6 (sk)

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EP01202215		2001-06-11
PCT/EP2002/006185 WO2002100865A1 (en)	2001-06-11	2002-06-05	Benzoxazepine derivatives and their use as ampa receptor stimulators

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SK287150B6 true SK287150B6 (sk)	2010-01-07

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EP (1)	EP1399450B1 (is)
JP (1)	JP4435561B2 (is)
KR (1)	KR100863255B1 (is)
CN (1)	CN1257908C (is)
AR (1)	AR036092A1 (is)
AT (1)	ATE389659T1 (is)
AU (1)	AU2002314144B2 (is)
BR (1)	BR0210222A (is)
CA (1)	CA2450274C (is)
CO (1)	CO5550447A2 (is)
CZ (1)	CZ300052B6 (is)
DE (1)	DE60225689T2 (is)
EC (1)	ECSP034891A (is)
ES (1)	ES2301651T3 (is)
HR (1)	HRP20031007A2 (is)
HU (1)	HUP0400154A3 (is)
IL (2)	IL158905A0 (is)
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MX (1)	MXPA03011563A (is)
NO (1)	NO328705B1 (is)
NZ (1)	NZ529670A (is)
PE (1)	PE20030097A1 (is)
PL (1)	PL366721A1 (is)
RU (1)	RU2279434C2 (is)
SK (1)	SK287150B6 (is)
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US7345036B2 (en)	2001-06-14	2008-03-18	N.V. Organon	(Pyrido/thieno)—[f]—oxazepine-5-one derivatives
WO2010054336A2 (en) *	2008-11-10	2010-05-14	The Regents Of The University Of California	Therapeutic uses of ampa receptor modulators for treatment of motor dysfunction
DK2483278T3 (da) *	2009-09-28	2014-01-13	Hoffmann La Roche	Benzoxazepin pi3k-inhibitorforbindelser og deres anvendelse i behandlingen af cancer
FR2964969B1 (fr)	2010-09-16	2012-08-24	Servier Lab	Nouveaux derives dihydrobenzoxathiazepines, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
EP3008167A4 (en)	2013-06-13	2017-06-07	VeroScience LLC	Compositions and methods for treating metabolic disorders
WO2018009256A1 (en)	2016-03-29	2018-01-11	Respirerx Pharmaceuticals, Inc.	Compositions and methods for treating attention deficit disorders
US10821103B2 (en)	2016-11-07	2020-11-03	Arbutus Biopharma Corporation	Substituted pyridinone-containing trycyclic compounds, and methods using same
WO2019177937A1 (en)	2018-03-12	2019-09-19	Arbutus Biopharma, Inc.	Substituted 2-pyridone tricyclic compounds, analogues thereof, and methods using same
KR20200142529A (ko)	2018-04-12	2020-12-22	아뷰터스 바이오파마 코포레이션	치환된 피리디논-함유 트리사이클릭 화합물의 제조 방법
AU2019382521B2 (en)	2018-11-22	2023-11-16	Fujian Akeylink Biotechnology Co., Ltd.	Crystal form of hepatitis B surface antigen inhibitor
EP4121072A1 (en) *	2020-03-20	2023-01-25	Amathus Therapeutics, Inc.	Cyclic sulfonamide derivatives as trap1 modulators and uses thereof

Family Cites Families (9)

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Publication number	Priority date	Publication date	Assignee	Title
GB1238719A (is)	1968-11-01	1971-07-07
CA2138533C (en)	1992-07-24	2009-04-14	Gary S. Lynch	Drugs that enhance synaptic responses mediated by ampa receptors
CN1168140A (zh)	1995-01-06	1997-12-17	弗·哈夫曼-拉罗切有限公司	羟甲基咪唑并二氮杂䓬及其酯
US5650409A (en) *	1995-06-02	1997-07-22	Cortex Pharmaceuticals, Inc.	Benzoyl piperidines/pyrrolidines for enhancing synaptic response
US5736543A (en) *	1996-04-03	1998-04-07	The Regents Of The University Of California	Benzoxazines for enhancing synaptic response
DE69831446T2 (de)	1997-06-09	2006-06-14	Pfizer Prod Inc	Chinazolin-4-on AMPA Antagonisten
US5985871A (en)	1997-12-24	1999-11-16	Cortex Pharmaceuticals, Inc.	Benzoxazine compounds for enhancing synaptic response
CA2320354A1 (en) *	1998-02-18	1999-08-26	Neurosearch A/S	Novel compounds and their use as positive ampa receptor modulators
US6124278A (en)	1998-04-03	2000-09-26	The Regents Of The University Of California	Acylbenzoxazines for enhancing synaptic response

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Also Published As

Publication number	Publication date
AR036092A1 (es)	2004-08-11
HRP20031007A2 (en)	2005-10-31
EP1399450B1 (en)	2008-03-19
JP4435561B2 (ja)	2010-03-17
CZ20033376A3 (en)	2004-04-14
CZ300052B6 (cs)	2009-01-21
CA2450274C (en)	2010-12-21
CA2450274A1 (en)	2002-12-19
ATE389659T1 (de)	2008-04-15
TWI232863B (en)	2005-05-21
SK15182003A3 (sk)	2004-05-04
CO5550447A2 (es)	2005-08-31
PL366721A1 (en)	2005-02-07
CN1257908C (zh)	2006-05-31
BR0210222A (pt)	2004-04-13
US7504390B2 (en)	2009-03-17
RU2004100310A (ru)	2005-06-10
US7307073B2 (en)	2007-12-11
EP1399450A1 (en)	2004-03-24
IL158905A (en)	2008-12-29
AU2002314144B2 (en)	2008-01-31
HUP0400154A2 (hu)	2004-07-28
JP2004533466A (ja)	2004-11-04
WO2002100865A1 (en)	2002-12-19
US20040171605A1 (en)	2004-09-02
KR100863255B1 (ko)	2008-10-15
NO328705B1 (no)	2010-05-03
NZ529670A (en)	2006-02-24
PE20030097A1 (es)	2003-02-08
ZA200309382B (en)	2005-03-02
ECSP034891A (es)	2004-01-28
NO20035486D0 (no)	2003-12-10
HK1061858A1 (en)	2004-10-08
DE60225689T2 (de)	2008-07-17
CN1514835A (zh)	2004-07-21
DE60225689D1 (de)	2008-04-30
KR20040006030A (ko)	2004-01-16
MXPA03011563A (es)	2004-03-18
ES2301651T3 (es)	2008-07-01
IS2526B (is)	2009-07-15
RU2279434C2 (ru)	2006-07-10
HUP0400154A3 (en)	2007-05-02
IL158905A0 (en)	2004-05-12
US20080139529A1 (en)	2008-06-12
IS7036A (is)	2003-11-13

Publication	Publication Date	Title
US7504390B2 (en)	2009-03-17	Benzoxazepine derivatives and their use as AMPA receptor stimulators
AU2002314144A1 (en)	2003-05-15	Benzoxazepine derivatives and their use as AMPA receptor stimulators
US8034804B2 (en)	2011-10-11	(Pyrido/thieno)-[f]-oxazepine-5-one derivatives
AU2002320841A1 (en)	2003-05-15	(Pyrido/thieno)-[f]-oxazepin-5-one derivatives as positive modulators of the AMPA receptor
HK1061858B (en)	2008-05-16	Benzoxazepine derivatives and their use as ampa receptor stimulators

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2013-03-01	MM4A	Patent lapsed due to non-payment of maintenance fees	Effective date: 20120605