NO318731B1 - Tropanderivater, farmasoytiske preparater som omfatter forbindelsene, anvendelse av forbindelsene til fremstilling av medikamenter og fremgangsmate for fremstilling av forbindelsene. - Google Patents

Tropanderivater, farmasoytiske preparater som omfatter forbindelsene, anvendelse av forbindelsene til fremstilling av medikamenter og fremgangsmate for fremstilling av forbindelsene. Download PDF

Info

Publication number: NO318731B1
Authority: NO; Norway
Prior art keywords: tropane; dichlorophenyl; normethyl; chlorophenyl; methoxymethyl
Prior art date: 1996-02-22

Application number

NO19983877A

Other languages

English (en)

Norwegian (no)

Other versions

NO983877D0 (no

NO983877L (no

Inventor

Peter Moldt

Jorgen Scheel-Krueger

Frank Watjen

Original Assignee

Neurosearch As

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.)

1996-02-22

Filing date

1998-08-21

Publication date

2005-05-02

1998-08-21 Application filed by Neurosearch As filed Critical Neurosearch As

1998-08-21 Publication of NO983877D0 publication Critical patent/NO983877D0/no

1998-08-21 Publication of NO983877L publication Critical patent/NO983877L/no

2005-05-02 Publication of NO318731B1 publication Critical patent/NO318731B1/no

Links

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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
- 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
- A61P25/14—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
- A61P25/24—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
- A61P25/36—Opioid-abuse
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Neurosurgery (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Psychiatry (AREA)
Addiction (AREA)
Hospice & Palliative Care (AREA)
Diabetes (AREA)
Child & Adolescent Psychology (AREA)
Hematology (AREA)
Obesity (AREA)
Psychology (AREA)
Pain & Pain Management (AREA)
Emergency Medicine (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

NO19983877A 1996-02-22 1998-08-21 Tropanderivater, farmasoytiske preparater som omfatter forbindelsene, anvendelse av forbindelsene til fremstilling av medikamenter og fremgangsmate for fremstilling av forbindelsene. NO318731B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DK19496		1996-02-22
PCT/EP1997/000850 WO1997030997A1 (fr)	1996-02-22	1997-02-21	Derives du tropane, leur preparation et utilisation

Publications (3)

Publication Number	Publication Date
NO983877D0 NO983877D0 (no)	1998-08-21
NO983877L NO983877L (no)	1998-08-21
NO318731B1 true NO318731B1 (no)	2005-05-02

Family

ID=8090830

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19983877A NO318731B1 (no)	1996-02-22	1998-08-21	Tropanderivater, farmasoytiske preparater som omfatter forbindelsene, anvendelse av forbindelsene til fremstilling av medikamenter og fremgangsmate for fremstilling av forbindelsene.

Country Status (31)

Country	Link
US (3)	US6288079B1 (fr)
EP (2)	EP1130020A1 (fr)
JP (1)	JP3238414B2 (fr)
KR (1)	KR100446571B1 (fr)
CN (1)	CN1077574C (fr)
AT (1)	ATE203023T1 (fr)
AU (1)	AU720358B2 (fr)
BG (1)	BG63945B1 (fr)
BR (1)	BR9707636A (fr)
CA (1)	CA2244773C (fr)
CZ (1)	CZ287007B6 (fr)
DE (1)	DE69705608T2 (fr)
DK (1)	DK0885220T3 (fr)
EE (1)	EE04751B1 (fr)
ES (1)	ES2159839T3 (fr)
GR (1)	GR3036829T3 (fr)
HU (1)	HU228356B1 (fr)
IL (1)	IL125146A (fr)
IS (1)	IS1824B (fr)
NO (1)	NO318731B1 (fr)
NZ (1)	NZ330886A (fr)
PL (1)	PL185132B1 (fr)
PT (1)	PT885220E (fr)
RU (1)	RU2167876C2 (fr)
SG (1)	SG99853A1 (fr)
SI (1)	SI0885220T1 (fr)
SK (1)	SK281813B6 (fr)
TR (1)	TR199801641T2 (fr)
UA (1)	UA49872C2 (fr)
WO (1)	WO1997030997A1 (fr)
ZA (1)	ZA971525B (fr)

Families Citing this family (78)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6486323B1 (en) *	1998-09-30	2002-11-26	Nihon Medi-Physics Co., Ltd.	Process for producing optically active tropinonemonocarboxylic acid derivative
AUPP627498A0 (en)	1998-10-02	1998-10-22	University Of Queensland, The	Novel peptides - i
EP1397358A1 (fr) *	2001-05-23	2004-03-17	Neurosearch A/S	Derives du tropane et utilisation de ces derniers comme inhibiteurs de recaptage du neurotransmetteur monoamine
DE20203103U1 (de) *	2001-10-11	2002-07-11	Organix, Inc., Woburn, Mass.	Serotonin-Wiederaufnahme-Inhibitoren
US20030114475A1 (en) *	2001-10-31	2003-06-19	Addiction Therapies, Inc.	Methods for the treatment of addiction
WO2003045388A1 (fr) *	2001-11-30	2003-06-05	Neurosearch A/S	Derives de tropane possedant une activite inhibitrice de recaptage de dopamine destines au traitement de maladies ischemiques
EP1513529B1 (fr) *	2002-05-30	2011-12-14	NeuroSearch A/S	Triple inhibiteurs de recaptage de momoamine pour le traitement de douleur chronique
AU2003277827A1 (en)	2002-11-01	2004-05-25	Neurosearch A/S	Novel piperidine derivatives and their use as monoamine neurotransmitter re-uptake inhibitors
WO2004050690A1 (fr)	2002-12-02	2004-06-17	Xenome Ltd	Nouveaux peptides (-i) de $g(x)-conotoxine
EP2412719A1 (fr)	2002-12-02	2012-02-01	Xenome Ltd	Pptides de chi-conotoxine
CN100372850C (zh) *	2003-02-12	2008-03-05	神经研究公司	新的8-氮杂-双环[3.2.1]辛烷衍生物和它们作为单胺神经递质再摄取抑制剂的用途
CN100551924C (zh) *	2003-02-12	2009-10-21	神经研究公司	8-氮杂-双环[3.2.1]辛烷衍生物和它们作为单胺神经递质再摄取抑制剂的用途
JP2006517568A (ja)	2003-02-12	2006-07-27	ニューロサーチ、アクティーゼルスカブ	８−アザ−ビシクロ［３．２．１］オクタン誘導体及びこれをモノアミン神経伝達物質再取り込み阻害薬として使用する方法
JP2006517567A (ja)	2003-02-12	2006-07-27	ニューロサーチ、アクティーゼルスカブ	新規８−アザ−ビシクロ［３．２．１］オクタン誘導体及びこれをモノアミン神経伝達物質再取り込み阻害薬として使用する方法
RU2344136C2 (ru) *	2003-06-24	2009-01-20	НьюроСёрч А/С	Новые производные 8-аза-бицикло[3.2.1]октана и их применение в качестве ингибиторов обратного захвата моноаминовых нейротрансмиттеров
AR045141A1 (es) *	2003-07-31	2005-10-19	Neurosearch As	Sales de tartrato de 2- metoximetil-3-(3,4-diclorofenil)-8-azabiciclo (3,2,1) octano. composiciones farmaceuticas que los contienen y usos de las mismas.
EP1682545B1 (fr)	2003-10-03	2007-12-12	Pfizer Limited	Derives de tropane a substitution imidazopyridine en tant qu'antagonistes des recepteurs ccr5 pour le traitement du vih et de l'inflammation
JP2007508336A (ja) *	2003-10-16	2007-04-05	ニューロサーチ、アクティーゼルスカブ	モノアミン神経伝達物質再取り込みインヒビター及びアセチルコリンエステラーゼインヒビターを含む医薬組成物
NZ547880A (en) *	2003-11-18	2010-02-26	Boehringer Ingelheim Int	Solid pharmaceutical preparation form
WO2005070427A1 (fr)	2004-01-22	2005-08-04	Neurosearch A/S	Composes utilises pour perdre du poids de maniere durable
AU2005205882A1 (en) *	2004-01-22	2005-08-04	Neurosearch A/S	Pharmaceutical composition comprising a monoamine neurotransmitter re-uptake inhibitor and an N-methyl-D-aspartate (NMDA) receptors antagonist
WO2005070428A1 (fr) *	2004-01-22	2005-08-04	Boehringer Ingelheim International Gmbh	Composition pharmaceutique contenant un inhibiteur de la recapture de neurotransmetteurs monoamine et un agoniste de la dopamine
DE102004004965B4 (de) *	2004-01-31	2006-01-05	Boehringer Ingelheim Pharma Gmbh & Co. Kg	Verfahren zur Herstellung eines 2-(Ethoxymethyl)-tropanderivates
JP2008501656A (ja) *	2004-06-04	2008-01-24	ノイロサーチアクティーゼルスカブ	β−アミロイド（Ａβ４０及びＡβ４２）生成阻害のためのモノアミン神経伝達物質再取り込み阻害剤
US7524958B2 (en)	2004-06-18	2009-04-28	Neurosearch A/S	Certain 9-aza-bicyclo[3.3.1] nonane derivatives and their use as monoamine neurotransmitter re-uptake inhibitors
JP2008502651A (ja)	2004-06-18	2008-01-31	ノイロサーチアクティーゼルスカブ	モノアミン神経伝達物質再取込み阻害剤としての、新規アルキル置換ピペリジン誘導体及びその使用
WO2005123728A1 (fr) *	2004-06-18	2005-12-29	Neurosearch A/S	Nouveaux derives de 9-aza-bicyclo[3.3.1]nonane et leur utilisation comme inhibiteurs du recaptage des neurotransmetteurs monoamines
KR20070061846A (ko)	2004-09-30	2007-06-14	뉴로서치 에이/에스	신규한 크로멘-2-온 유도체 및 모노아민 신경전달물질재흡수 억제제로서의 이의 용도
AU2005288914B2 (en) *	2004-09-30	2011-05-19	Neurosearch A/S	Novel chromen-2-one derivatives and their use as monoamine neurotransmitter re-uptake inhibitors
DE602006007550D1 (de)	2005-02-10	2009-08-13	Neurosearch As	Alkylsubstituierte homopiperazinderivate und deren verwendung als monoamin neurotransmitter wiederaufnahmeinhibitoren
WO2006106090A1 (fr) *	2005-04-04	2006-10-12	Neurosearch A/S	Nouveaux derives diazabicyclo substitues et leur utilisation comme inhibiteurs du recaptage des neurotransmetteurs monoamines
US20090137625A1 (en)	2005-04-08	2009-05-28	Dan Peters	Novel Enantiomers and Their Use as Monoamine Neurotransmitter Re-Uptake Inhibitors
US8093388B2 (en) *	2005-06-28	2012-01-10	Neurosearch A/S	3-aza spiro[5,5]undec-8-ene derivatives and their use as monoamine neurotransmitter re-uptake inhibitors
EP1899301B1 (fr) *	2005-06-28	2010-09-15	NeuroSearch A/S	Nouveaux derives de 3-aza-spiro[5.5]undec-8-ene et leur utilisation en tant qu'inhibiteurs de recaptage de neurotransmetteur de monoamine
WO2007000465A1 (fr) *	2005-06-28	2007-01-04	Neurosearch A/S	Nouveaux derives de 3-aza-spiro[5.5]undecane et leur utilisation comme inhibiteurs de la recapture des neurotransmetteurs monoaminergiques
EP1917264B1 (fr) *	2005-06-28	2010-11-17	NeuroSearch A/S	Nouveaux derives 3,9-diaza-spiro[5.5]undecane et leur utilisation en tant qu'inhibiteurs du recaptage du neurotransmitteur monoamine
WO2007006738A2 (fr) *	2005-07-12	2007-01-18	Boehringer Ingelheim International Gmbh	Composition pharmaceutique utile dans le traitement des troubles de la libido
UA95454C2 (uk)	2005-07-15	2011-08-10	Амр Текнолоджи, Інк.	Арил- і гетероарилзаміщені тетрагідробензазепіни і їх застосування для блокування зворотного захоплення норепінефрину, допаміну і серотоніну
WO2007025055A2 (fr)	2005-08-24	2007-03-01	Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services	Composes de benztropine et leurs utilisations
WO2007028769A1 (fr) *	2005-09-05	2007-03-15	Neurosearch A/S	Inhibiteur de recaptage de neurotransmetteur monoamine pour la neuroprotection
WO2007028770A1 (fr) *	2005-09-05	2007-03-15	Neurosearch A/S	Inhibiteurs du recaptage du neurotransmetteur monoamine pour une neuroprotection chez des patients souffrant d'une maladie mentale avancée
EP1779851A1 (fr)	2005-10-31	2007-05-02	Boehringer Ingelheim Pharma GmbH & Co.KG	Traitement du diabète
TW200804367A (en)	2005-11-11	2008-01-16	Neurosearch As	Novel compounds
CN101379063A (zh)	2006-02-10	2009-03-04	神经研究公司	3,9-二氮杂双环[3.3.1]壬烷衍生物及其作为单胺神经递质再摄取抑制剂的用途
TW200800980A (en)	2006-02-17	2008-01-01	Neurosearch As	Novel compounds
US20100234349A1 (en)	2006-09-04	2010-09-16	Olsen Gunnar M	Pharmaceutical combinations of a nicotine receptor modulator and a cognitive enhancer
BRPI0716532A2 (pt) *	2006-09-11	2013-09-24	Glaxo Group Ltd	compostos azabicÍclios como inidores de reabsorÇço de monoaminas
GB0703998D0 (en) *	2007-03-01	2007-04-11	Glaxo Group Ltd	Novel salt
TW200904815A (en)	2007-05-09	2009-02-01	Neurosearch As	Novel compounds
US20100286195A1 (en) *	2007-09-10	2010-11-11	Neurosearch A/S	Novel benzooxazol-and benzooxathiol-2-one derivatives and their use as monoamine neurotransmitter re-uptake inhibitors
WO2009034043A1 (fr) *	2007-09-10	2009-03-19	Neurosearch A/S	Nouveaux dérivés de phénoxazin-3-one et leur utilisation comme inhibiteurs de la recapture des neurotransmetteurs monoamines
EP2222303A1 (fr) *	2007-11-20	2010-09-01	NeuroSearch A/S	Procédé de traitement de l'accoutumance
WO2009065845A1 (fr) *	2007-11-20	2009-05-28	Neurosearch A/S	Procédé de traitement des troubles d'hyperphagie
AU2010247763B2 (en)	2009-05-12	2015-12-24	Albany Molecular Research, Inc.	7-([1,2,4,]triazolo[1,5,-a]pyridin-6-yl)-4-(3,4-dichlorophenyl)-1,2,3,4- tetrahydroisoquinoline and use thereof
US8815894B2 (en)	2009-05-12	2014-08-26	Bristol-Myers Squibb Company	Crystalline forms of (S)-7-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydroisoquinoline and use thereof
US8697721B2 (en)	2009-05-15	2014-04-15	Aniona Aps	Chromen-2-one derivatives and their use as monoamine neurotransmitter re-uptake inhibitors
WO2011032903A1 (fr)	2009-09-21	2011-03-24	Neurosearch A/S	Dérivés de pipérazinyl-alkyl-benzoimidazol-2-one et leur utilisation comme inhibiteurs de recaptage de neurotransmetteurs monoamines
WO2011092061A1 (fr)	2010-01-29	2011-08-04	Neurosearch A/S	Dérivés du chromen-2-one et leur utilisation comme inhibiteurs de la recapture des neurotransmetteurs monoamines
WO2011117289A1 (fr)	2010-03-25	2011-09-29	Neurosearch A/S	Dérivés de chromén-2-one et leur utilisation à titre d'inhibiteurs de recaptage des neurotransmetteurs monoaminés
US8153653B2 (en) *	2010-06-22	2012-04-10	Hoffmann-La Roche Inc.	Amido-tropane derivatives
WO2012000881A1 (fr)	2010-07-02	2012-01-05	Neurosearch A/S	Dérivés de chromén-2-one et leur utilisation comme inhibiteurs de la résorption de neurotransmetteurs monoamine
WO2012024397A2 (fr)	2010-08-17	2012-02-23	Albany Molecular Research, Inc.	Dérivés 2,5-méthano- et 2,5-éthano-tétrahydrobenzazépine et utilisation de ceux-ci pour bloquer le recaptage de la norépinéphrine, de la dopamine, et de la sérotonine
EP2625170A1 (fr)	2010-10-07	2013-08-14	Takeda Pharmaceutical Company Limited	Dérivés de 1,4-oxazépane
HRP20190050T1 (hr)	2012-02-16	2019-03-08	Saniona A/S	Farmaceutski pripravci za kombinacijsku terapiju
PE20180187A1 (es)	2015-03-03	2018-01-23	Saniona As	Formulacion de combinacion de tesofensina y betabloqueante
EA026727B1 (ru) *	2015-09-10	2017-05-31	Замертон Холдингс Лимитед	Соль (1r,2r,3s)-3-(3,4-дихлорфенил)-2-(этоксиметил)-8-метил-8-азабицикло[3.2.1]октана и фталевой кислоты, способ её получения, продукт способа, фармацевтические композиции для лечения и/или профилактики нарушений, связанных с ожирением, их применение и способы лечения и/или профилактики нарушений, связанных с ожирением
US20190060301A1 (en)	2016-01-15	2019-02-28	Saniona A/S	Tesofensine and metoprolol for treatment of hypertension
EA028995B1 (ru) *	2016-02-25	2018-01-31	Замертон Холдингс Лимитед	Соль тезофензина и оптически активных ацетиламинокислот, их применение для лечения и/или профилактики нарушений, связанных с ожирением
AU2017324406A1 (en) *	2016-09-07	2019-05-02	Saniona A/S	Tesofensine compositions
DE102017210141A1 (de)	2017-06-16	2018-12-20	Henkel Ag & Co. Kgaa	Portion zur Bereitstellung tensidhaltiger Flotten
MX2021008208A (es)	2019-01-07	2021-11-17	Saniona As	Tesofensina para la reduccion del peso corporal para pacientes con sindrome de prader-willi.
MX2022013236A (es)	2020-04-22	2023-01-24	Saniona As	Tratamiento de la obesidad hipotalamica.
TWI772928B (zh) *	2020-10-21	2022-08-01	行政院原子能委員會核能研究所	非放射性標準品β-CFT之製備方法
AU2023303077A1 (en)	2022-07-08	2025-02-06	Initiator Pharma A/S	Compound for treatment of female sexual dysfunction
CN115572289A (zh) *	2022-10-24	2023-01-06	龙曦宁（上海）医药科技有限公司	一种特索芬辛的合成方法
JP2026512649A (ja)	2022-10-28	2026-04-20	イニシエーターファーマエー／エス	疼痛の治療用化合物
TW202440106A (zh)	2023-01-03	2024-10-16	丹麥商創始人製藥股份有限公司	用於治療勃起障礙之化合物
WO2025051846A1 (fr)	2023-09-05	2025-03-13	Initiator Pharma A/S	Composé pour le traitement d'un dysfonctionnement sexuel féminin

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4281130A (en) *	1979-05-24	1981-07-28	Sterling Drug Inc.	Lower-alkyl 4,6,7,8,8a-9-hexahydro-6,9-ethanothieno[3,2-f]indolizine-10-carboxylate
US5128118A (en) *	1990-08-09	1992-07-07	Research Triangle Institute	Cocaine receptor binding ligands
US5496953A (en)	1990-08-09	1996-03-05	Research Triangle Institute	Cocaine receptor binding ligands
US5380848A (en) *	1990-08-09	1995-01-10	Research Triangle Institute	Cocaine receptor binding ligands
DK0644775T3 (da) *	1991-11-15	2000-03-06	Nat Inst Health	Kokainreceptorbindende ligander
AU671163B2 (en) *	1992-12-23	1996-08-15	Neurosearch A/S	Alkyl substituted heterocyclic compounds
AU672052B2 (en)	1992-12-23	1996-09-19	Neurosearch A/S	Antidepressant and antiparkinsonian compounds
AU672644B2 (en) *	1992-12-23	1996-10-10	Neurosearch A/S	Aryl substituted heterocyclic compounds
BR9507489A (pt) *	1994-04-19	1997-08-12	Neurosearch As	Derivados tropano sua preparacão e uso
GB9626611D0 (en) *	1996-12-20	1997-02-05	Unilever Plc	Agglomerated silicas

1997
- 1997-02-21 JP JP52981097A patent/JP3238414B2/ja not_active Expired - Fee Related
- 1997-02-21 WO PCT/EP1997/000850 patent/WO1997030997A1/fr not_active Ceased
- 1997-02-21 BR BR9707636A patent/BR9707636A/pt not_active IP Right Cessation
- 1997-02-21 CN CN97192505A patent/CN1077574C/zh not_active Expired - Fee Related
- 1997-02-21 CZ CZ19982520A patent/CZ287007B6/cs not_active IP Right Cessation
- 1997-02-21 EE EE9800254A patent/EE04751B1/xx not_active IP Right Cessation
- 1997-02-21 UA UA98073814A patent/UA49872C2/uk unknown
- 1997-02-21 SK SK929-98A patent/SK281813B6/sk not_active IP Right Cessation
- 1997-02-21 CA CA002244773A patent/CA2244773C/fr not_active Expired - Lifetime
- 1997-02-21 SI SI9730163T patent/SI0885220T1/xx unknown
- 1997-02-21 HU HU9901199A patent/HU228356B1/hu not_active IP Right Cessation
- 1997-02-21 DE DE69705608T patent/DE69705608T2/de not_active Expired - Lifetime
- 1997-02-21 TR TR1998/01641T patent/TR199801641T2/xx unknown
- 1997-02-21 KR KR10-1998-0706518A patent/KR100446571B1/ko not_active Expired - Fee Related
- 1997-02-21 NZ NZ330886A patent/NZ330886A/xx not_active IP Right Cessation
- 1997-02-21 SG SG9903902A patent/SG99853A1/en unknown
- 1997-02-21 IL IL12514697A patent/IL125146A/en not_active IP Right Cessation
- 1997-02-21 EP EP01108256A patent/EP1130020A1/fr not_active Withdrawn
- 1997-02-21 EP EP97903355A patent/EP0885220B1/fr not_active Expired - Lifetime
- 1997-02-21 RU RU98117314/04A patent/RU2167876C2/ru active
- 1997-02-21 PL PL97328503A patent/PL185132B1/pl not_active IP Right Cessation
- 1997-02-21 AT AT97903355T patent/ATE203023T1/de active
- 1997-02-21 AU AU17940/97A patent/AU720358B2/en not_active Ceased
- 1997-02-21 DK DK97903355T patent/DK0885220T3/da active
- 1997-02-21 US US09/101,524 patent/US6288079B1/en not_active Expired - Lifetime
- 1997-02-21 PT PT97903355T patent/PT885220E/pt unknown
- 1997-02-21 ES ES97903355T patent/ES2159839T3/es not_active Expired - Lifetime
- 1997-02-21 ZA ZA9701525A patent/ZA971525B/xx unknown
1998
- 1998-07-15 BG BG102637A patent/BG63945B1/bg unknown
- 1998-08-17 IS IS4825A patent/IS1824B/is unknown
- 1998-08-21 NO NO19983877A patent/NO318731B1/no not_active IP Right Cessation
2001
- 2001-03-21 US US09/814,413 patent/US6395748B2/en not_active Expired - Fee Related
- 2001-10-08 GR GR20010401690T patent/GR3036829T3/el unknown
2002
- 2002-03-15 US US10/099,642 patent/US20020128284A1/en not_active Abandoned

Also Published As

Publication number	Publication date
HU228356B1 (en)	2013-03-28
JP2000504739A (ja)	2000-04-18
US20010018444A1 (en)	2001-08-30
IS4825A (is)	1998-08-17
PL185132B1 (pl)	2003-02-28
DE69705608T2 (de)	2002-05-16
ES2159839T3 (es)	2001-10-16
US6395748B2 (en)	2002-05-28
EE04751B1 (et)	2006-12-15
IS1824B (is)	2002-10-01
CA2244773C (fr)	2006-01-03
KR100446571B1 (ko)	2004-11-03
NO983877D0 (no)	1998-08-21
CN1077574C (zh)	2002-01-09
IL125146A (en)	2002-03-10
PL328503A1 (en)	1999-02-01
NZ330886A (en)	1999-02-25
BR9707636A (pt)	1999-07-27
BG63945B1 (bg)	2003-07-31
CA2244773A1 (fr)	1997-08-28
EP0885220B1 (fr)	2001-07-11
SK92998A3 (en)	1998-11-04
NO983877L (no)	1998-08-21
US20020128284A1 (en)	2002-09-12
GR3036829T3 (en)	2002-01-31
EE9800254A (et)	1999-02-15
DE69705608D1 (de)	2001-08-16
UA49872C2 (uk)	2002-10-15
CZ252098A3 (cs)	1998-11-11
CN1211982A (zh)	1999-03-24
RU2167876C2 (ru)	2001-05-27
IL125146A0 (en)	1999-01-26
ZA971525B (en)	1997-10-21
CZ287007B6 (en)	2000-08-16
PT885220E (pt)	2001-11-30
HUP9901199A2 (hu)	1999-08-30
AU1794097A (en)	1997-09-10
SK281813B6 (sk)	2001-08-06
EP1130020A1 (fr)	2001-09-05
SI0885220T1 (en)	2001-12-31
HUP9901199A3 (en)	2001-02-28
HK1018957A1 (en)	2000-01-14
KR19990087127A (ko)	1999-12-15
ATE203023T1 (de)	2001-07-15
AU720358B2 (en)	2000-06-01
TR199801641T2 (xx)	1998-11-23
BG102637A (en)	1999-06-30
SG99853A1 (en)	2003-11-27
JP3238414B2 (ja)	2001-12-17
US6288079B1 (en)	2001-09-11
DK0885220T3 (da)	2001-10-15
WO1997030997A1 (fr)	1997-08-28
EP0885220A1 (fr)	1998-12-23

Legal Events

Date	Code	Title	Description
2014-09-22	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
NO318731B1 (no)	2005-05-02	Tropanderivater, farmasoytiske preparater som omfatter forbindelsene, anvendelse av forbindelsene til fremstilling av medikamenter og fremgangsmate for fremstilling av forbindelsene.
NO309569B1 (no)	2001-02-19	Fusjonerte tropanderivater som inhiberer for neurotransmitteropptak
SK28798A3 (en)	1998-09-09	8-azabicyclo[3.2.1]oct-2-ene derivatives, their preparation and use
LV11738B (en)	1997-12-20	Tropane-2-aldoxime derivatives as neurotransmitter reuptake inhibitors
EP0981515B1 (fr)	2003-08-27	Derives de la piperidine utilises comme inhibiteurs du recaptage des neurotransmetteurs
NO301227B1 (no)	1997-09-29	Arylsubstituerte, heterosykliske forbindelser, anvendelser derav og farmasöytisk preparat som omfatter en slik forbindelse
NO301164B1 (no)	1997-09-22	Alkylsubstituerte, heterosykliske forbindelser, anvendelser derav og farmasöytisk preparat som omfatter en slik forbindelse
MXPA98003554A (en)	1998-11-16	Frozen tropan derivatives, its preparation and