DK1664050T3 - Neurobeskyttende bicykliske forbindelser og farmaceutiske sammensætninger, der indeholder dem - Google Patents

Neurobeskyttende bicykliske forbindelser og farmaceutiske sammensætninger, der indeholder dem Download PDF

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Publication number
DK1664050T3
DK1664050T3 DK04782733.2T DK04782733T DK1664050T3 DK 1664050 T3 DK1664050 T3 DK 1664050T3 DK 04782733 T DK04782733 T DK 04782733T DK 1664050 T3 DK1664050 T3 DK 1664050T3
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substituted
aryl
heteroalkyl
alkyl
alkenyl
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DK04782733.2T
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Margaret Anne Brimble
Jian Guan
Frank Sieg
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Neuren Pharmaceuticals Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • 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
    • A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular 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
    • 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
    • A61P25/14—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
    • A61P25/24—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
    • 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
    • A61P35/00—Antineoplastic agents
    • 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
    • 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
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/10—Spiro-condensed systems

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Pain & Pain Management (AREA)
  • Psychology (AREA)
  • Epidemiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Psychiatry (AREA)
  • Rheumatology (AREA)
  • Urology & Nephrology (AREA)
  • Hospice & Palliative Care (AREA)
  • Pulmonology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Vascular Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Claims (8)

1. Forbindelse med formlen:
eller et farmaceutisk acceptabelt salt eller hydrat deraf, hvor X1 er valgt fra gruppen bestående af NR', O og S; X2 er valgt fra gruppen bestående af CH2, NR', O og S; R1 er valgt fra gruppen bestående af -OR', -SR', -NR'R', -NO2, -CN, -C(0)R', -C(0)0R', -C(0)NR'R', -C(NR')NR'R', trihalogenmethyl, halogen, alkyl, substitueret alkyl, heteroalkyl, substitueret heteroalkyl, alkenyl, substitueret alkenyl, al-kynyl, substitueret alkynyl, aryl, substitueret aryl, heteroaryl, substitueret hetero-aryl, arylalkyl, substitueret arylalkyl, heteroarylalkyl og substitueret heteroarylal-kyl; hvert R' er uafhængigt valgt fra gruppen bestående af -H, alkyl, heteroalkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl og heteroarylalkyl; R2, R3, R4 og R5 er uafhængigt valgt fra gruppen bestående af -H, -OR', -SR', -NR’R’, -NO2, -CN, -C(0)R\ -C(0)0R\ -C(0)NR'R', -C(NR')NR Ή’, trihalogenmethyl, halogen, alkyl, substitueret alkyl, heteroalkyl, substitueret heteroalkyl, alkenyl, substitueret alkenyl, alkynyl, substitueret alkynyl, aryl, substitueret aryl, heteroaryl, substitueret heteroaryl, arylalkyl, substitueret arylalkyl, heteroarylalkyl og substitueret heteroarylalkyl; hvert R1 er uafhængigt valgt fra gruppen bestående af -H, alkyl, heteroalkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl og heteroarylalkyl; eller R4 og R5 taget sammen er -CH2-(CH2)n-CH2-, hvor n er et heltal fra 0 til 6; eller R2 og R3 taget sammen er -CH2-(CH2)n-CH2-, hvor n er et heltal fra 0 til 6; med det forbehold, at når R1=methyl, og R2=R3=R4=H, så er R5 φ benzyl; hvor en substitueret alkyl-, substitueret heteroalkyl-, substitueret alkenyl-, substitueret alkynyl-, substitueret aryl-, substitueret heteroaryl- eller substitueret arylal-kylgruppe er en alkyl-, heteroalkyl-, alkenyl-, alkynyl-, aryl-, heteroaryl- eller aryl-alkylgruppe, hvor et eller flere af hydrogenatomerne er uafhængigt erstattet med en anden substituent, som indbefatter -R', -OR', -SR', -NR'R', -NO2, -CN, -C(O)-R', -C(0)0R', -C(0)NR'R', -C(NR’)NR'R', -NR'-C(NR')-OR', -NR'-C(NR')-SR', NR'-C(NR')-NR'R', trihalogenmethyl og halogen, hvor hvert R' uafhængigt er -H, alkyl, heteroalkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl eller heteroarylalkyl.
2. Forbindelse ifølge krav 1, hvor R1=methyl eller allyl.
3. Forbindelse ifølge krav 1, hvor R2=R3=methyl, og X2=S.
4. Forbindelse ifølge krav 1, hvor R1=allyl, R2=R3=R4=R5=H, X1=NH, og X2=-CFI2 (cyklisk G-2AllylP); eller hvor R1=methyl, R2=R3=H, R4 og R5 taget sammen er -CH2-(CH2)3-CH2-, X1=NH, og X2=CFl2 (cyklisk cyclohexyl-G2MeP); eller hvor R1=methyl, R2=R3=H, R4 og R5 taget sammen er -CH2-(CH2)2-CH2-, X1=NH, og X2=CFl2 (cyklisk cyclopentyl-G2MeP).
5. Farmaceutisk sammensætning, som omfatter en forbindelse ifølge et hvilket som helst af de foregående krav og en farmaceutisk acceptabel excipiens.
6. En eller flere forbindelser ifølge et hvilket som helst af kravene 1 -4 til anvendelse til beskyttelse af neuroner, som ellers vil degenerere eller dø som følge af en skade eller en sygdom.
7. En eller flere forbindelser til anvendelse ifølge krav 6, hvor sygdommen er kendetegnet ved apoptotisk neurondød, nekrotisk neuroncelledød, neuroncelle-degenerering, eller hvor skaden resulterer i nekrotisk neuroncelledød, apoptotisk neuroncelledød eller neuroncelledegenerering.
8. En eller flere forbindelser til anvendelse ifølge krav 6, hvor forbindelsen er valgt blandt cyklisk G-2AllylP, cyklisk cyclohexyl-G-2MeP og cyklisk cyclopentyl-G-2MeP.
DK04782733.2T 2003-09-03 2004-08-31 Neurobeskyttende bicykliske forbindelser og farmaceutiske sammensætninger, der indeholder dem DK1664050T3 (da)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US49995603P 2003-09-03 2003-09-03
PCT/US2004/028308 WO2005023815A2 (en) 2003-09-03 2004-08-31 Neuroprotective bicyclic compounds and methods for their use

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DK1664050T3 true DK1664050T3 (da) 2016-03-07

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US (2) US8067425B2 (da)
EP (1) EP1664050B1 (da)
JP (1) JP4842817B2 (da)
DK (1) DK1664050T3 (da)
ES (1) ES2564803T3 (da)
HU (1) HUE028528T2 (da)
PL (1) PL1664050T3 (da)
SI (1) SI1664050T1 (da)
WO (1) WO2005023815A2 (da)

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Publication number Publication date
JP2007504235A (ja) 2007-03-01
EP1664050A2 (en) 2006-06-07
EP1664050B1 (en) 2015-12-09
WO2005023815A2 (en) 2005-03-17
US20060258663A1 (en) 2006-11-16
US8067425B2 (en) 2011-11-29
US7776876B2 (en) 2010-08-17
JP4842817B2 (ja) 2011-12-21
US20070197511A1 (en) 2007-08-23
PL1664050T3 (pl) 2016-08-31
ES2564803T3 (es) 2016-03-29
HUE028528T2 (en) 2016-12-28
WO2005023815A3 (en) 2005-07-21
SI1664050T1 (sl) 2016-04-29

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