EP1102748A1 - Nouvelle 4-amino-1-aryl-pyridine-2-one a proprietes anticonvulsivantes et son procede de fabrication - Google Patents

Nouvelle 4-amino-1-aryl-pyridine-2-one a proprietes anticonvulsivantes et son procede de fabrication

Info

Publication number
EP1102748A1
EP1102748A1 EP99941472A EP99941472A EP1102748A1 EP 1102748 A1 EP1102748 A1 EP 1102748A1 EP 99941472 A EP99941472 A EP 99941472A EP 99941472 A EP99941472 A EP 99941472A EP 1102748 A1 EP1102748 A1 EP 1102748A1
Authority
EP
European Patent Office
Prior art keywords
amιno
general formula
compounds
pyπdιn
pyrιdιn
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP99941472A
Other languages
German (de)
English (en)
Inventor
Hans-Joachim Lankau
Klaus Unverferth
Thomas Arnold
Reni Bartsch
Angelika Rostock
Vladimir Granik
Sofia Grizik
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Elbion GmbH
Original Assignee
Arzneimittelwerk Dresden GmbH
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
Application filed by Arzneimittelwerk Dresden GmbH filed Critical Arzneimittelwerk Dresden GmbH
Publication of EP1102748A1 publication Critical patent/EP1102748A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/73—Unsubstituted amino or imino radicals
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • 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
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
    • C07D213/46—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/26—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms

Definitions

  • the invention relates to new 4-amino-1-aryl-pyrid-2-one, processes for their preparation and their use as medicaments, in particular for the treatment of various forms of epilepsy
  • the invention is therefore based on the object of making available new compounds with favorable pharmacological properties which can be used in particular as medicaments having an antiepileptic effect
  • these new compounds are 4-amino-1-aryl-pyrid-2-one of the general formula 1
  • X hydrogen, C-
  • -C4-alkoxy, T ⁇ fluormethyl, T ⁇ fluormethoxy or halogen and A amino, C-
  • the compounds of general formula 1 can by a new method by reacting the compounds of general formula 2
  • X hydrogen, -C -C 4 alkyl, C-
  • R C 1 -C 4 alkyl
  • Py ⁇ midine derivatives of the general formula 2 can be synthesized in a simple manner (Chem Heterocycl Compd, 24 (8), (1988), 914-919, Khim Geterotsikl Soedin, 8, (1988), 1109-1114)
  • the compounds of the general formula 1 are prepared in two process stages, py ⁇ midine derivatives of the general formula 2 in an alkaline medium, preferably in 5 to 50 percent sodium hydroxide solution, 0.1 to 10 hours, preferably one hour, at 50 ° C. to 150 ° C.
  • the mixture is then heated to 100 ° C. to 200 ° C. with strong acids, preferably 50 to 98 percent sulfuric acid, for 10 to 30 minutes by known methods.
  • the primary amino group can be mono- or dialkylated using known methods , 4-D ⁇ brombutan, 1, 5-D ⁇ brompentan or D ⁇ - (2-chloroethyl) ether
  • the compounds of general formula 1 according to the invention are suitable for the preparation of pharmaceutical compositions. These pharmaceutical compositions contain at least one of the compounds of general formula 1 according to the invention
  • the medicaments can be used, for example, parenterally (for example intravenously, intramuscularly subcutaneously) or orally.
  • parenterally for example intravenously, intramuscularly subcutaneously
  • the appropriate forms of application are produced by methods which are generally known and customary in pharmaceutical practice
  • the compounds according to the invention were in vivo after ip application to mice or after (po application) to rats according to the international standard (Pharmac Weekblad, Sc Ed 14, 132 (1992) and Antiepileptic Drugs, Third Ed, Raven Press, New York 1989) tested for their anticonvulsant activity (Table 1)
  • known antiepileptics either work in the model maximum electric shock only at higher doses or have stronger, undesirable (neurotoxic) side effects
  • a 4-aminopyridin-2-one (example 1-15) prepared according to the general synthesis instructions is alkylated with a suitable alkylating agent such as dimethyl sulfate or di (2-chloroethyl) ether in the presence of sodium methylate.
  • a suitable alkylating agent such as dimethyl sulfate or di (2-chloroethyl) ether in the presence of sodium methylate.
  • the reaction mixture is introduced into water.
  • the precipitate is separated off and recrystallized.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biomedical Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Psychiatry (AREA)
  • Pain & Pain Management (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

L'invention concerne une nouvelle 4-amino-1-aryl-pyridine-2-one de formule (1), dans laquelle n = 0, 1, 2, 3, 4, 5 et X désigne un hydrogène, un alkyle en C1-C4, un alcoxy en C1-C4, un trifluorométhyle, trifluorométhoxy ou un halogène, et A désigne un amino, un alkylamino en C1-C4, un dialkylamino en C1-C4, morpholino, pipéridino ou pyrrolidino. L'invention concerne également son procédé de fabrication, ainsi que son utilisation comme médicament pour le traitement de différentes formes d'épilepsie.
EP99941472A 1998-08-07 1999-07-28 Nouvelle 4-amino-1-aryl-pyridine-2-one a proprietes anticonvulsivantes et son procede de fabrication Withdrawn EP1102748A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE19835918 1998-08-07
DE19835918A DE19835918A1 (de) 1998-08-07 1998-08-07 Neue antikonvulsiv wirkende 4-Amino-1-aryl-pyridin-2-one und Verfahren zu deren Herstellung
PCT/EP1999/005399 WO2000007988A1 (fr) 1998-08-07 1999-07-28 Nouvelle 4-amino-1-aryl-pyridine-2-one a proprietes anticonvulsivantes et son procede de fabrication

Publications (1)

Publication Number Publication Date
EP1102748A1 true EP1102748A1 (fr) 2001-05-30

Family

ID=7876889

Family Applications (1)

Application Number Title Priority Date Filing Date
EP99941472A Withdrawn EP1102748A1 (fr) 1998-08-07 1999-07-28 Nouvelle 4-amino-1-aryl-pyridine-2-one a proprietes anticonvulsivantes et son procede de fabrication

Country Status (21)

Country Link
US (1) US6071911A (fr)
EP (1) EP1102748A1 (fr)
JP (1) JP2002522420A (fr)
KR (1) KR20010074802A (fr)
CN (1) CN1322197A (fr)
AR (1) AR021186A1 (fr)
AU (1) AU5507499A (fr)
BG (1) BG105196A (fr)
BR (1) BR9912849A (fr)
CA (1) CA2279692C (fr)
DE (1) DE19835918A1 (fr)
HU (1) HUP0103204A3 (fr)
IL (1) IL141200A0 (fr)
NO (1) NO20010575L (fr)
NZ (1) NZ509914A (fr)
PL (1) PL346013A1 (fr)
RU (1) RU2001106634A (fr)
SK (1) SK2002001A3 (fr)
TR (1) TR200100370T2 (fr)
WO (1) WO2000007988A1 (fr)
ZA (1) ZA200100999B (fr)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2320973T3 (es) 2000-06-12 2009-06-01 EISAI R&D MANAGEMENT CO., LTD. Compuestos de 1,2-dihidropiridina, procedimiento para su preparacion y uso de los mismos.
GB0129260D0 (en) 2001-12-06 2002-01-23 Eisai London Res Lab Ltd Pharmaceutical compositions and their uses
MY148809A (en) 2004-07-06 2013-05-31 Eisai R&D Man Co Ltd Crystals of 1,2-dihydropyridine compound and their production process
KR20210107644A (ko) 2018-12-14 2021-09-01 에자이 알앤드디 매니지먼트 가부시키가이샤 1,2-디하이드로피리딘 화합물의 수성 기반 약학적 제형

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS51118768A (en) * 1975-02-19 1976-10-18 Shigeo Senda Method for preparing 4-amino-2-pyridone derivatives
EP0110091B1 (fr) * 1982-10-27 1987-01-21 Degussa Aktiengesellschaft Dérivés de la 2-amino-3-acylamino-6-benzylamino-pyridine à activité antiépileptique

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0007988A1 *

Also Published As

Publication number Publication date
KR20010074802A (ko) 2001-08-09
AU5507499A (en) 2000-02-28
NO20010575L (no) 2001-04-04
JP2002522420A (ja) 2002-07-23
BR9912849A (pt) 2001-05-08
SK2002001A3 (en) 2002-01-07
CN1322197A (zh) 2001-11-14
CA2279692A1 (fr) 2000-02-07
NO20010575D0 (no) 2001-02-02
AR021186A1 (es) 2002-07-03
ZA200100999B (en) 2001-12-14
HUP0103204A3 (en) 2002-06-28
TR200100370T2 (tr) 2001-08-21
DE19835918A1 (de) 2000-02-10
NZ509914A (en) 2002-11-26
HUP0103204A2 (hu) 2002-04-29
PL346013A1 (en) 2002-01-14
BG105196A (en) 2001-12-29
US6071911A (en) 2000-06-06
IL141200A0 (en) 2002-02-10
RU2001106634A (ru) 2004-02-27
WO2000007988A1 (fr) 2000-02-17
CA2279692C (fr) 2003-10-07

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