FI108723B - Förfarande för framställning av 6-esterderivat av terapeutiskt avändbara 4a,5,9,10,11,12-hexahydro-11-metyl-6H-bensofuro[3a,3,2-ef][2]bensazepin-3,6-diol - Google Patents

Förfarande för framställning av 6-esterderivat av terapeutiskt avändbara 4a,5,9,10,11,12-hexahydro-11-metyl-6H-bensofuro[3a,3,2-ef][2]bensazepin-3,6-diol Download PDF

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FI108723B
FI108723B FI944821A FI944821A FI108723B FI 108723 B FI108723 B FI 108723B FI 944821 A FI944821 A FI 944821A FI 944821 A FI944821 A FI 944821A FI 108723 B FI108723 B FI 108723B
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formula
compound
give
chloroform
mmol
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FI944821A
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English (en)
Finnish (fi)
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FI944821A0 (sv
FI944821A (sv
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Larry Davis
Veronica Taberna
Jr Raymond W Kosley
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Aventis Pharma Inc
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D491/00Heterocyclic 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
    • C07D491/02Heterocyclic 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
    • C07D491/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D491/00Heterocyclic 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
    • C07D491/02Heterocyclic 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
    • C07D491/10Spiro-condensed systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D491/00Heterocyclic 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
    • C07D491/02Heterocyclic 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
    • C07D491/06Peri-condensed systems

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

Claims (4)

1. Förfarande för framställning av terapeutiskt användbara 6-esterderivat av 4a,5,9,10,11,12-hexahydro-11-5 metyl-6H-bensofuro[3a,3,2-ef][2]bensazepin-3,6-diol eller farmaceutiskt godtagbara salter därav, OR2 JL o .OH ra> V CH3 15 där R2 är (C3-C6) alkenylkarbonyl, (C3-C8) cykloalkyl- karbonyl, (C3-C8) cykloalkylarainokarbonyl, (C3-C6) alkynyl- karbonyl, (C3-C6) cykloalkyl-(C-l-C.^) alkylkarbonyl, adaman-tylkarbonyl, adamantylmetylkarbonyl, pyridyl, tetrahydro- 20 isokinolylkarbonyl, morfolinokarbonyl, halogen(C1-C6)alkyl-sulfonyl eller (C^-Cg) alkylsilyl, * ' kännetecknat därav, att | (a) galantamin med formeln (III) 25 ch,o :i' rV°vVH
30 N-^ / ch3 O-demetyleras, varvid erhälls en förening med formeln (IV) 35 37 1 08723 OH 0γ0τύ: N—^ CH3 io (b) om sä önskas, omsätts föreningen, som har for- meln (IV), med ett lämpligt cykloalkylisocyanat, varvid erhälls en förening med formeln (II) , där R2 är (C3-C8) cykloalkylaminokarbonyl, (c) om sd önskas, omsätts föreningen, som har for-15 mein (IV), med en lämplig karboxylsyrahalogenid, varvid ! erhälls en förening med formeln (II) , där R är (C3-C8) alkenylkarbonyl, (C3-C6) alkynylkarbonyl eller (C3 -C8) cykloalkylkarbonyl, (d) om sd önskas, omsätts föreningen, som har for-20 mein (IV), med ett lämpligt halogenpyridin, varvid erhälls en förening med formeln (II), där R2 är pyridyl, (e) om sä önskas, omsätts föreningen, som har for- , ; mein (IV), med en lämplig alkylsilylhalogenid, varvid er- . / hälls en förening med formeln (II) , där R2 är (C^-Cg) - l 25 alkylsilyl, *·*; (f) om sä önskas, omsätts föreningen, som har for- • · · ·*·: mein (IV) , med en lämplig sulfonsyraanhydrid, varvid er- halls en förening med formeln (II) , där R2 är halogen- (Οχ - Cs) alkylsulf onyl, 30 (g) om sä önskas, omsätts föreningen, som har for- ”*: mein (IV), med ett lämpligt koppi ingsmedel, säsom 1,1- . karbonyldiimidazol eller dicyklohexyldikarbodiimid, ooh en ‘ ; lämplig karboxylsyra, tetrahydroisokinolin eller morfolin, varvid erhälls en förening med formeln (II), där R2 är 35 (C3-C8) cykloalkylkarbonyl, adamantylkarbonyl, adamantyl- metylkarbonyl, tetrahydroisokinolylkarbonyl eller morfo-linokarbonyl. 33 1 08723
2. Förfarande enligt patentkrav 1, kanne- t e c k n a t därav, att man framställer en förening med formeln (II), där R2 är (C3_6)-alkenylkarbonyl, (C3_6) - alkynylkarbonyl, (C3_8) -cykloalkylkarbonyl, (C3.8)-cykloal- 5 kyl-(C1_12) -alkylkarbonyl, pyridyl, morfolinokarbonyl eller tetrahydroisokinolylkarbonyl.
3. Förfarande enligt patentkrav 1, kanne-t e c k n a t därav, att man framställer en förening med formeln (II), där R2 är cyklopropylkarbonyl, cyklobutyl- 10 karbonyl, cyklohexylkarbonyl, metylcyklohexylkarbonyl, adamantylmetylkarbonyl, 2-metylpropenylkarbonyl, 2- propynylkarbonyl, cykloheptylaminokarbonyl, cyklohexyl-aminokarbonyl, morfolinokarbonyl eller tetrahydroisokino-linylkarbonyl. 15
4. Förfarande enligt patentkrav 1, känne- t e c k n a t därav, att man framställer (6-O-demetyl)-6-0-(1,2,3,4-tetrahydroisokinolin-2-yl)karbonylgalantamin eller ett farmaceutiskt godtagbart syraadditiossalt därav. ϊ * ! * * • · * t f \ t » * I t t · · » ! I » M M | »
FI944821A 1993-10-15 1994-10-13 Förfarande för framställning av 6-esterderivat av terapeutiskt avändbara 4a,5,9,10,11,12-hexahydro-11-metyl-6H-bensofuro[3a,3,2-ef][2]bensazepin-3,6-diol FI108723B (sv)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US13744093 1993-10-15
US08/137,440 US6323195B1 (en) 1993-10-15 1993-10-15 Galanthamine derivatives as acetylcholinesterase inhibitors

Publications (3)

Publication Number Publication Date
FI944821A0 FI944821A0 (sv) 1994-10-13
FI944821A FI944821A (sv) 1995-04-16
FI108723B true FI108723B (sv) 2002-03-15

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FI944821A FI108723B (sv) 1993-10-15 1994-10-13 Förfarande för framställning av 6-esterderivat av terapeutiskt avändbara 4a,5,9,10,11,12-hexahydro-11-metyl-6H-bensofuro[3a,3,2-ef][2]bensazepin-3,6-diol

Country Status (23)

Country Link
US (2) US6323195B1 (sv)
EP (2) EP0653427B1 (sv)
JP (1) JP2664344B2 (sv)
KR (1) KR0169114B1 (sv)
CN (1) CN1039911C (sv)
AT (1) ATE212348T1 (sv)
AU (1) AU696249B2 (sv)
CA (1) CA2118174C (sv)
CZ (1) CZ287071B6 (sv)
DE (1) DE69429708T2 (sv)
DK (1) DK0653427T3 (sv)
EG (1) EG20472A (sv)
ES (1) ES2171428T3 (sv)
FI (1) FI108723B (sv)
IL (1) IL111274A (sv)
NO (1) NO310415B1 (sv)
NZ (1) NZ264683A (sv)
PL (1) PL177730B1 (sv)
PT (1) PT653427E (sv)
RO (1) RO114133B1 (sv)
RU (1) RU2114850C1 (sv)
TW (1) TW363969B (sv)
ZA (1) ZA948062B (sv)

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GB9514821D0 (en) * 1995-07-19 1995-09-20 Sod Conseils Rech Applic Galanthamine derivatives
AT403803B (de) 1996-04-19 1998-05-25 Sanochemia Ltd Neue benzazepinderivate, diese enthaltende arzneimittel und verwendung derselben zum herstellen von arzneimitteln
WO2000030446A1 (en) * 1998-11-23 2000-06-02 Bonnie Davis Dosage formulations for acetylcholinesterase inhibitors
CA2358062C (en) 1998-12-24 2006-12-19 Janssen Pharmaceutica N.V. Controlled release galantamine composition
ATE355066T1 (de) * 1999-01-11 2006-03-15 Atanas Russinov Djananov Nahrungszusatz aus kräutern zur steigerung der muskulären kraft und ausdauer von athleten
US8603546B2 (en) * 1999-01-11 2013-12-10 Herbaceuticals Inc. Herbal supplement for increased muscle strength and endurance for athletes
US6372760B1 (en) * 1999-03-31 2002-04-16 Eisai Co., Ltd. Stabilized composition comprising antidementia medicament
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US6670356B2 (en) 1999-12-10 2003-12-30 Bonnie Davis Analogs of galanthamine and lycoramine as modulators of nicotinic receptors
DE50101827D1 (de) 2000-03-31 2004-05-06 Sanochemia Pharmazeutika Ag Wi Neue derivate und analoga von galanthamin
US20030162770A1 (en) * 2002-02-22 2003-08-28 Davis Bonnie M. Use of modulators of nicotinic receptors for treatment of cognitive dysfunction
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WO2005065661A2 (en) * 2003-12-31 2005-07-21 Actavis Group Hf Immediate, controlled and sustained release formulations of galanthamine
CA2552114A1 (en) * 2003-12-31 2005-07-21 Actavis Group Hf Solid dosage formulations of galantamine
US20080045500A1 (en) * 2004-07-01 2008-02-21 Eisai R&D Management Co., Ltd. Nerve Regeneration Stimulator
PL1895994T3 (pl) * 2005-05-13 2011-02-28 Alza Corp Wielowarstwowy system podawania leków z barierą zabezpieczającą przed wypływaniem materiału ze zbiornika
US20080188510A1 (en) * 2005-05-23 2008-08-07 Eisai R & D Management Co., Ltd. Novel methods using zonisamide
ATE473219T1 (de) * 2005-09-22 2010-07-15 Galantos Pharma Gmbh Cholinerge enhancer mit verbesserter durchgängigkeit durch die blut-hirn-schranke zur behandlung von krankheiten, die mit kognitiven störungen einhergehen
EP1777222A1 (en) 2005-09-22 2007-04-25 Galantos Pharma GmbH Cholinergic enhancers with improved blood-brain barrier permeability for the treatment of diseases accompanied by cognitive impairment
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WO2007035941A2 (en) * 2005-09-23 2007-03-29 Alza Corporation Transdermal galantamine delivery system
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Also Published As

Publication number Publication date
NZ264683A (en) 1998-03-25
NO943893D0 (no) 1994-10-14
PL177730B1 (pl) 2000-01-31
CZ287071B6 (en) 2000-08-16
TW363969B (en) 1999-07-11
DE69429708D1 (de) 2002-03-14
ES2171428T3 (es) 2002-09-16
KR950011443A (ko) 1995-05-15
CA2118174A1 (en) 1995-04-16
JPH07188240A (ja) 1995-07-25
NO943893L (no) 1995-04-18
IL111274A0 (en) 1994-12-29
ZA948062B (en) 1995-06-06
KR0169114B1 (ko) 1999-01-15
NO310415B1 (no) 2001-07-02
US5777108A (en) 1998-07-07
CZ254694A3 (en) 1995-09-13
PL305456A1 (en) 1995-04-18
RU94036448A (ru) 1996-09-10
EG20472A (en) 1999-05-31
DK0653427T3 (da) 2002-04-15
CA2118174C (en) 2000-01-18
ATE212348T1 (de) 2002-02-15
AU696249B2 (en) 1998-09-03
EP0653427B1 (en) 2002-01-23
CN1039911C (zh) 1998-09-23
RO114133B1 (ro) 1999-01-29
FI944821A0 (sv) 1994-10-13
IL111274A (en) 2000-11-21
FI944821A (sv) 1995-04-16
CN1111245A (zh) 1995-11-08
DE69429708T2 (de) 2002-08-29
EP1020470A3 (en) 2000-07-26
JP2664344B2 (ja) 1997-10-15
EP0653427A1 (en) 1995-05-17
EP1020470A2 (en) 2000-07-19
AU7581494A (en) 1995-05-04
RU2114850C1 (ru) 1998-07-10
US6323195B1 (en) 2001-11-27
PT653427E (pt) 2002-06-28

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GB Transfer or assigment of application

Owner name: HOECHST MARION ROUSSEL, INC.

PC Transfer of assignment of patent

Owner name: AVENTISUB II INC.

Free format text: AVENTISUB II INC.

MA Patent expired