DK1636221T3 - 3-Heterocyclyl-azetidin-forbindelser, som er nytte som NK1/NK2 receptorantagonister - Google Patents

3-Heterocyclyl-azetidin-forbindelser, som er nytte som NK1/NK2 receptorantagonister

Info

Publication number
DK1636221T3
DK1636221T3 DK04736475T DK04736475T DK1636221T3 DK 1636221 T3 DK1636221 T3 DK 1636221T3 DK 04736475 T DK04736475 T DK 04736475T DK 04736475 T DK04736475 T DK 04736475T DK 1636221 T3 DK1636221 T3 DK 1636221T3
Authority
DK
Denmark
Prior art keywords
heterocyclyl
receptor antagonists
compounds useful
azetidine compounds
azetidine
Prior art date
Application number
DK04736475T
Other languages
Danish (da)
English (en)
Inventor
Anders Johansson
Joachim Persson
Original Assignee
Albireo Ab
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 claimed from SE0301744A external-priority patent/SE0301744D0/xx
Priority claimed from SE0303493A external-priority patent/SE0303493D0/xx
Application filed by Albireo Ab filed Critical Albireo Ab
Application granted granted Critical
Publication of DK1636221T3 publication Critical patent/DK1636221T3/da

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D205/04—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
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    • 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
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
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    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
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    • A61P25/00—Drugs for disorders of the nervous system
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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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    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
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    • 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
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • 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
    • A61P37/08—Antiallergic agents
    • 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
    • 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
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C233/76—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by doubly-bound oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C255/57—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and carboxyl groups, other than cyano groups, bound to the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C255/58—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton
    • C07C255/60—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton at least one of the singly-bound nitrogen atoms being acylated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/04—One of the condensed rings being a six-membered aromatic ring
    • C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Immunology (AREA)
  • Pulmonology (AREA)
  • Psychiatry (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Urology & Nephrology (AREA)
  • Hospice & Palliative Care (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Hematology (AREA)
  • Psychology (AREA)
  • Diabetes (AREA)
  • Addiction (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Obesity (AREA)
  • Dermatology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Otolaryngology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
DK04736475T 2003-06-13 2004-06-09 3-Heterocyclyl-azetidin-forbindelser, som er nytte som NK1/NK2 receptorantagonister DK1636221T3 (da)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
SE0301744A SE0301744D0 (sv) 2003-06-13 2003-06-13 New compounds
SE0303493A SE0303493D0 (sv) 2003-12-19 2003-12-19 New compounds
PCT/SE2004/000901 WO2004110344A2 (fr) 2003-06-13 2004-06-09 Nouveaux composés d'azétidine

Publications (1)

Publication Number Publication Date
DK1636221T3 true DK1636221T3 (da) 2009-10-12

Family

ID=33554614

Family Applications (1)

Application Number Title Priority Date Filing Date
DK04736475T DK1636221T3 (da) 2003-06-13 2004-06-09 3-Heterocyclyl-azetidin-forbindelser, som er nytte som NK1/NK2 receptorantagonister

Country Status (24)

Country Link
US (1) US7402581B2 (fr)
EP (1) EP1636221B1 (fr)
JP (1) JP4982886B2 (fr)
KR (1) KR20060021373A (fr)
AR (1) AR044662A1 (fr)
AT (1) ATE439358T1 (fr)
AU (1) AU2004246983B2 (fr)
BR (1) BRPI0411285A (fr)
CA (1) CA2529126C (fr)
CO (1) CO5640122A2 (fr)
DE (1) DE602004022546D1 (fr)
DK (1) DK1636221T3 (fr)
ES (1) ES2330522T3 (fr)
HK (1) HK1088004A1 (fr)
IL (1) IL171894A (fr)
IS (1) IS8228A (fr)
MX (1) MXPA05013276A (fr)
MY (1) MY146599A (fr)
NO (1) NO332109B1 (fr)
PL (1) PL1636221T3 (fr)
PT (1) PT1636221E (fr)
RU (1) RU2356888C2 (fr)
TW (1) TW200508221A (fr)
WO (1) WO2004110344A2 (fr)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE0403005D0 (sv) * 2004-12-09 2004-12-09 Astrazeneca Ab New use
CN101208327A (zh) * 2005-06-23 2008-06-25 阿斯利康(瑞典)有限公司 作为神经激肽受体拮抗剂用于治疗胃肠疾病的新氮杂环丁烷衍生物
CN101203511A (zh) * 2005-06-23 2008-06-18 阿斯利康(瑞典)有限公司 作为神经激肽受体拮抗剂用于治疗胃肠疾病的新氮杂环丁烷衍生物
AR057828A1 (es) 2005-09-29 2007-12-19 Astrazeneca Ab Compuestos derivados de azetidina, su preparacion y composicion farmaceuutica
AR056087A1 (es) * 2005-09-29 2007-09-19 Astrazeneca Ab Derivados de azetidina como antagonistas de receptores de neuroquina nk
WO2007043938A1 (fr) * 2005-10-07 2007-04-19 Astrazeneca Ab Nouvelle forme cristalline de 3,5-dibromo-n-[(2s)-2-(4-fluorophenyl)-4-(3-morpholin-4-ylazetidin-1-yl)butyl]-n-methylbenzamide, modification b
WO2007043939A1 (fr) * 2005-10-07 2007-04-19 Astrazeneca Ab Nouvelle forme cristalline de 3,5-dibromo-n-[(2s)-2-(4-fluorophenyl)-4-(3-morpholin-4-ylazetidin-1-yl)butyl]-n-methylbenzamide, modification a
WO2007136325A1 (fr) * 2006-05-18 2007-11-29 Astrazeneca Ab Dérivés de 1-[(4-[benzoyl(méthyl)amino]-3-(phényl)butyl]azétidine destinés au traitement de troubles gastro-intestinaux 2
WO2007136326A2 (fr) * 2006-05-18 2007-11-29 Astrazeneca Ab Nouveaux composés 302
US8106208B2 (en) 2006-05-18 2012-01-31 Albireo Ab Benzamide compounds that act as NK receptor antagonists
CL2007002097A1 (es) * 2006-07-20 2008-01-18 Smithkline Beecham Corp Compuestos derivados de pirrolidina o morfolina antagonistas de urotensina ii; composicion farmaceutica que comprende a dichos compuestos; y su uso para tratar insuficiencia cardiaca congestiva, insuficiencia cardiaca isquemica, angina, isquemia del miocardio, vejiga hiperactiva, asma y/o copd, entre otras.
CN101506199A (zh) * 2006-08-15 2009-08-12 埃科特莱茵药品有限公司 用作食欲素受体拮抗剂的氮杂环丁烷化合物
WO2008076042A1 (fr) * 2006-12-19 2008-06-26 Astrazeneca Ab Dérivés d'azétidinepipérazine qui sont des antagonistes du récepteur de neurokinine (nk), et leur utilisation
WO2008076041A1 (fr) * 2006-12-19 2008-06-26 Albireo Ab Dérivés de l'azetidinazabicyclo [3.2.1] octane qui sont des antagonistes du récepteur de la neurokinine (nk) et utilisation de ces derniers
KR101558005B1 (ko) 2007-03-08 2015-10-06 알비레오 에이비 2-치환-3-페닐프로피온산 유도체 및 염증성 장 질환 치료에서의 그의 용도
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NO332109B1 (no) 2012-06-25
WO2004110344A2 (fr) 2004-12-23
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TW200508221A (en) 2005-03-01
JP4982886B2 (ja) 2012-07-25
EP1636221B1 (fr) 2009-08-12
PT1636221E (pt) 2009-11-05
JP2006527267A (ja) 2006-11-30
US20060172988A1 (en) 2006-08-03
CA2529126C (fr) 2011-11-08
MXPA05013276A (es) 2006-03-09
US7402581B2 (en) 2008-07-22
ES2330522T3 (es) 2009-12-11
CA2529126A1 (fr) 2004-12-23
NO20060206L (no) 2006-03-13
IS8228A (is) 2006-01-11
ATE439358T1 (de) 2009-08-15
IL171894A (en) 2012-05-31
IL171894A0 (en) 2006-04-10
RU2005136535A (ru) 2006-07-27
CO5640122A2 (es) 2006-05-31
HK1088004A1 (en) 2006-10-27
WO2004110344A3 (fr) 2005-02-17
AU2004246983B2 (en) 2008-06-12
AR044662A1 (es) 2005-09-21
DE602004022546D1 (de) 2009-09-24
KR20060021373A (ko) 2006-03-07
AU2004246983A1 (en) 2004-12-23
RU2356888C2 (ru) 2009-05-27
PL1636221T3 (pl) 2010-01-29
MY146599A (en) 2012-08-30

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