FI106797B - Förfarande för framställning av azabicyklo [2.2.1] heptan-3-on-oximer - Google Patents

Förfarande för framställning av azabicyklo [2.2.1] heptan-3-on-oximer Download PDF

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Publication number
FI106797B
FI106797B FI941699A FI941699A FI106797B FI 106797 B FI106797 B FI 106797B FI 941699 A FI941699 A FI 941699A FI 941699 A FI941699 A FI 941699A FI 106797 B FI106797 B FI 106797B
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Prior art keywords
azabicyclo
heptan
oxime
propynyl
process according
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FI941699A
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English (en)
Finnish (fi)
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FI941699A (sv
FI941699A0 (sv
Inventor
David Jeffrey Lauffer
Walter Hamilton Moos
Michael Raymond Pavia
Haile Tecle
Anthony Jerome Thomas
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Warner Lambert Co
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Publication of FI941699A0 publication Critical patent/FI941699A0/sv
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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
    • C07D487/08—Bridged systems
    • 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
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • 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
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
    • 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
    • C07D451/04—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 with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
    • C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems

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

Claims (22)

1. Förfarande för framställning av som läkemedel använd-bara azabicyklo[2.2.l]heptan-3-onoximer med formeln I 25 c?yoR *··* N • * · * · « • « I i vilken formel R är :r 3 0 -CH2C=C-Ph1 eller -CH2-C=C-C=C-Ph . ·:::· i i H Rx . Ha Hb 1 5. vilka Pl^ är fenyl, vilken är substituerad med 1 eller 2 substituenter, vilka är en rak eller förgrenad alkyl med 106797 28 1-4 kolatomer, en rak eller förgrenad alkoxi med 1-4 kol-atomer, klor, fluor, trifluormetyl eller nitro, Ph är fenyl, R-l är en alkylgrupp med 1-4 kolatomer, 5 eller en enskild geometrisk eller optiskt aktiv isomer eller ett farmaceutiskt godtagbart salt därav, känneteck-nat därav, att en keton med formeln V €f N omsättes med en hydroxylamin med formeln 15 H2nor i vilken R betecknar detsamma som ovan, och för fram-ställning av ett oximsalt den erhällna föreningen med 20 formeln ;,; ' 25. vilken R betecknar detsamma som ovan, omsättes med en syra. ·»·» tl»
2. Förfarande enligt patentkravet 1, kännetecknat därav, att hydroxylaminderivatet med formeln -CH2C=C-Ph1 enligt ] ' 30 patentkravet 1 är ett hydroxylaminderivat med formeln » « 4 :··: H2N-0-CH2CsC-Ph1 1 vilken Ph2 är fenyl, vilken är substituerad med en 35 substituent, vilken är en rak alkyl med 1-4 kolatomer, en rak alkoxi med 1-4 kolatomer, klor eller fluor. 106797 29
3. Förfarande enligt patentkravet 2, kännetecknat därav, att man framställer Z-(±)-l-azabicyklo[2.2. l]heptan-3-on-O- (3 - (2 1 -metoxif enyl) -2-propynyl) oxim. 5 4. Förfarande enligt patentkravet 2, kännetecknat därav, att man framställer E-(±)-l-azabicyklo[2.2.1]heptan-3-on-O- (3 - (2 ' -metoxif enyl) -2-propynyl) oxim.
5. Förfarande enligt patentkravet 2, kännetecknat därav, 10 att man framställer Z-(±)-l-azabicyklo[2.2.1]heptan-3-on- 0-(3-(3 '-metoxifenyl) -2-propynyl)oxim.
6. Förfarande enligt patentkravet 2, kännetecknat därav, att man framställer E-(±)-l-azabicyklo[2.2.l]heptan-3-on-
15 O- (3- (3 ' -metoxifenyl) -2-propynyl) oxim.
7. Förfarande enligt patentkravet 2, kännetecknat därav, att man framställer Z-(±)-l-azabicyklo[2.2.1]heptan-3-on-O- (3 - (4' -metoxif enyl) -2-propynyl) oxim. 20
8. Förfarande enligt patentkravet 2, kännetecknat därav, . : : att man framställer E-(±)-l-azabicyklo[2.2.l]heptan-3-on- : : : 0-(3-(4 '-metoxifenyl)-2-propynyl)oxim. 25 9. Förfarande enligt patentkravet 2, kännetecknat därav, att man framställer Z-(±)-l-azabicyklo[2.2 . l]heptan-3-on- Ί j! O— (3 — (2' -klorf enyl) -2-propynyl) oxim. • « ·
10. Förfarande enligt patentkravet 2, kännetecknat därav, * ‘ 30 att man framställer E-(±)-l-azabicyklo[2.2.1]heptan-3-on- • « « 0-(3-(2 1-klorfenyl)-2-propynyl) oxim. # • ·
11. Förfarande enligt patentkravet 2, kännetecknat därav, att man framställer Z-(±)-l-azabicyklo[2.2.1]heptan-3-on-
35 O-(3-(3'-klorfenyl)-2-propynyl)oxim. 106797 30
12. Förfarande enligt patentkravet 2, kännetecknat därav, att man framställer E-(±)-l-azabicyklo[2.2.l]heptan-3-on-0-(3-(31-klorfenyl)-2-propynyl)oxim. 5 13. Förfarande enligt patentkravet 2, kännetecknat därav, att man framställer Z-(±)-l-azabicyklo[2.2.l]heptan-3-on-0-(3-(4'-klorfenyl)-2-propynyl)oxim.
14. Förfarande enligt patentkravet 2, kännetecknat därav, 10 att man framställer Z-(±)-l-azabicyklo[2.2.1]heptan-3-on- 0-(3-(4-fluorfenyl)-2-propynyl)oxim.
15. Förfarande enligt patentkravet 1, kännetecknat därav, att hydroxylaminderivatet med formeln 15 -CH2-C=C-C =C-Ph I ί H R: 20 enligt patentkravet 1 är ett hydroxylaminderivat med formeln ' : : H2N—o-ch2-c=c-c =C-Ph I I H R, 25 i vilken Rx och Ph betecknar detsamma som i patentkravet « « · « .·:*. i. « · · . 16. Förfarande enligt patentkravet 15, kännetecknat • · « o · * / 3 0 därav, att R: är en metylgrupp. • * ·;··· 17. Förfarande enligt patentkravet 15, kännetecknat ” därav, att man framställer Z-(±)-l-azabicyklo[2.2.l]hep- tan-3-on-O-(Z-3-metyl-5-fenyl-2-penten-4-ynyl)oxim. 1 Förfarande enligt patentkravet 15, kännetecknat 106797 31 därav, att man framställer E-(±)-l-azabicyklo[2.2.1]hep-tan-3-on-0-(Z-3-metyl-5-fenyl-2-penten-4-ynyl)oxim.
19. Förfarande enligt patentkravet 15, kännetecknat 5 därav, att man framställer Z-(±)-l-azabicyklo[2.2.l]hep-tan-3-on-O-(E-3-metyl-5-fenyl-2-penten-4-ynyl)oxim.
20. Förfarande enligt patentkravet 15, kännetecknat därav, att man framställer E- (±) -*l-azabicyklo[2.2. l]hep- 10 tan-3-on-O-(E-3-metyl-5-fenyl-2-penten-4-ynyl)oxim.
21. Förfarande enligt patentkravet 10, kännetecknat därav, att man framställer ett hydroklorid- eller oxalat-salt. 15 « < i t 1 t I I < I ; i i • M ···· • «I · • · · • · · • < » · · « · » « « » • · • · · .li ( f • I I
FI941699A 1991-10-16 1994-04-13 Förfarande för framställning av azabicyklo [2.2.1] heptan-3-on-oximer FI106797B (sv)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US77841291 1991-10-16
US07/778,412 US5306718A (en) 1990-03-06 1991-10-16 Oxime and amine substituted azabicyclo and azocyclo muscarinic agonists and methods of treatment
US9208642 1992-10-09
PCT/US1992/008642 WO1993008192A1 (en) 1991-10-16 1992-10-09 Azabicyclo arylacetylene and arylenyne oximes as cholinergic agents and methods of treatment

Publications (3)

Publication Number Publication Date
FI941699A FI941699A (sv) 1994-04-13
FI941699A0 FI941699A0 (sv) 1994-04-13
FI106797B true FI106797B (sv) 2001-04-12

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ID=25113261

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FI941699A FI106797B (sv) 1991-10-16 1994-04-13 Förfarande för framställning av azabicyklo [2.2.1] heptan-3-on-oximer

Country Status (17)

Country Link
US (2) US5306718A (sv)
EP (1) EP0608336B1 (sv)
JP (1) JP3367670B2 (sv)
KR (1) KR100241479B1 (sv)
AT (1) ATE166354T1 (sv)
AU (1) AU658685B2 (sv)
CA (1) CA2115443C (sv)
DE (1) DE69225601T2 (sv)
DK (1) DK0608336T3 (sv)
ES (1) ES2119823T3 (sv)
FI (1) FI106797B (sv)
NO (1) NO302072B1 (sv)
NZ (1) NZ244726A (sv)
PH (1) PH31431A (sv)
PT (1) PT100961B (sv)
WO (1) WO1993008192A1 (sv)
ZA (1) ZA927973B (sv)

Families Citing this family (15)

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US5346911A (en) * 1990-03-06 1994-09-13 Warner-Lambert Company Azabicyclo and azacyclo oxime and amine cholinergic agents and methods of treatment
US5514812A (en) * 1994-06-10 1996-05-07 Warner-Lambert Company Preparation of stereochemically pure oximes with muscarinic activity
AUPM910994A0 (en) * 1994-10-28 1994-11-24 Commonwealth Scientific And Industrial Research Organisation Bisallyloxyimides
US5534522A (en) * 1995-06-07 1996-07-09 Warner-Lambert Company (R)-(Z)-1-azabicyclo [2.2.1] heptan-3-one,O-[3-(3-methoxyphenyl)-2-propynyl] oxime maleate as a pharmaceutical agent
US6168912B1 (en) 1996-01-23 2001-01-02 Martek Biosciences Corporation Method and kit for making a multidimensional combinatorial chemical library
IL129793A (en) * 1997-01-27 2003-01-12 Warner Lambert Co Process for producing (z)-azabicyclo oxime ethers
US6677341B2 (en) * 1999-09-23 2004-01-13 Pharmacia Corporation (R)-Chiral halogenated substituted heteroaryl benzyl aminoalcohol compounds useful for inhibiting cholesteryl ester transfer protein activity
US6924313B1 (en) 1999-09-23 2005-08-02 Pfizer Inc. Substituted tertiary-heteroalkylamines useful for inhibiting cholesteryl ester transfer protein activity
ATE445838T1 (de) 2001-07-25 2009-10-15 Raptor Pharmaceutical Inc Zusammensetzungen und verfahren zur modulation des transports durch die blut-hirn-schranke
KR100465277B1 (ko) * 2002-01-24 2005-01-13 한국과학기술연구원 신규한 옥심계 아자 두 고리 화합물 및 그 제조방법
CA2789097C (en) 2005-04-28 2017-02-21 Proteus Digital Health, Inc. Pharma-informatics system
WO2008036682A2 (en) 2006-09-18 2008-03-27 Raptor Pharmaceutical Inc. Treatment of liver disorders by administration of receptor-associated protein (rap)-conjugates
NZ616673A (en) 2009-02-20 2014-08-29 To Bbb Holding B V Glutathione-based drug delivery system
NZ596876A (en) 2009-05-06 2014-01-31 Lab Skin Care Inc Dermal delivery compositions comprising active agent-calcium phosphate particle complexes and methods of using the same
US20120077778A1 (en) 2010-09-29 2012-03-29 Andrea Bourdelais Ladder-Frame Polyether Conjugates

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US3371094A (en) * 1961-08-08 1968-02-27 Sterling Drug Inc N-(amidoximino-lower-alkyl)-and n-amidino-n-[(1-piperidyl)-lower-alkyl]amines
US3502692A (en) * 1962-06-13 1970-03-24 American Cyanamid Co Cyclic nitroxides and process for preparing same
DE2019536A1 (de) * 1970-04-23 1971-11-11 Basf Ag Oximcarbamate
DE2552176A1 (de) * 1975-11-21 1977-06-02 Hoechst Ag Neue piperidin-derivate, ihre herstellung und verwendung
US4341795A (en) * 1975-12-01 1982-07-27 Union Carbide Corporation Asymmetrical bis-carbamate compounds
US4710508A (en) * 1986-12-08 1987-12-01 Warner-Lambert Company O-substituted tetrahydropyridine oxime cholinergic agents
NZ226000A (en) * 1987-09-10 1991-06-25 Merck Sharp & Dohme Oxadiazolyl-azabicycloheptanes and pharmaceutical compositions
US4937239A (en) * 1989-02-13 1990-06-26 Warner-Lambert Company Azabicycloalkane oxime & azabicycloalkene oxime muscarinic agents
IL97266A0 (en) * 1990-03-06 1992-05-25 Warner Lambert Co Azabicyclo and azacyclo oximes and amines,their preparation and pharmaceutical compositions containing them

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KR100241479B1 (ko) 2000-03-02
CA2115443A1 (en) 1993-04-29
ZA927973B (en) 1994-04-15
US5306718A (en) 1994-04-26
JPH07500337A (ja) 1995-01-12
DE69225601D1 (de) 1998-06-25
NZ244726A (en) 1995-09-26
ATE166354T1 (de) 1998-06-15
WO1993008192A1 (en) 1993-04-29
NO302072B1 (no) 1998-01-19
AU658685B2 (en) 1995-04-27
DE69225601T2 (de) 1998-12-17
CA2115443C (en) 2003-05-13
JP3367670B2 (ja) 2003-01-14
PH31431A (en) 1998-11-03
EP0608336A1 (en) 1994-08-03
US5482938A (en) 1996-01-09
ES2119823T3 (es) 1998-10-16
FI941699A (sv) 1994-04-13
DK0608336T3 (da) 1999-01-18
AU2783592A (en) 1993-05-21
NO941365D0 (no) 1994-04-15
NO941365L (no) 1994-04-15
PT100961B (pt) 1999-07-30
FI941699A0 (sv) 1994-04-13
PT100961A (pt) 1993-11-30
EP0608336B1 (en) 1998-05-20

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