EP1311510A1 - Antikonvulsiv wirkende 2,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one und verfahren zu deren darstellung - Google Patents

Antikonvulsiv wirkende 2,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one und verfahren zu deren darstellung

Info

Publication number
EP1311510A1
EP1311510A1 EP01960709A EP01960709A EP1311510A1 EP 1311510 A1 EP1311510 A1 EP 1311510A1 EP 01960709 A EP01960709 A EP 01960709A EP 01960709 A EP01960709 A EP 01960709A EP 1311510 A1 EP1311510 A1 EP 1311510A1
Authority
EP
European Patent Office
Prior art keywords
dihydro
pyrazolo
pyrimidin
methyl
phenyl
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Withdrawn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
EP01960709A
Other languages
German (de)
English (en)
French (fr)
Inventor
Thomas Arnold
Hans-Joachim Lankau
Klaus Unverferth
Christine Tober
Chris Rundfeldt
Rita Dost
Katrin BERNÖSTER
Antje Gasparic
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.)
AWD Pharma GmbH and Co KG
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 EP1311510A1 publication Critical patent/EP1311510A1/de
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants

Definitions

  • the invention relates to 2,5-dihydro-pyrazolo [3 ) 4-d] pyrimidin-4-ones and their tautomers which have an Ar (alkyl) radical in the 5-position and a hydrogen or an Ar (alkyl) in the 2-position ) -Rest contain, processes for their preparation and their use as medicines, in particular for the treatment of epilepsy of various forms.
  • Pyrazolo [3,4-d] pyrimidines are pharmacologically interesting compounds due to their structural similarities to adenine.
  • Known anticonvulsants have the disadvantage, on the one hand, that undesirable side effects such as neurotoxicity and idiosyncrasies occur and, on the other hand, they are not effective in certain forms of epilepsy.
  • the invention is therefore based on the object of providing compounds with favorable pharmacological properties which are anticonvulsant act and can be used as a medicine, in particular for the treatment of epilepsy.
  • these new compounds are 2,5-dihydropyrazolo [3,4-dlpyrimidin-4-ones of the general formula 1
  • R CH 2 -phenyl, in which phenyl can be substituted one or more times with halogen,
  • CrC 3 -alkyl straight-chain or branched, optionally mono- or polysubstituted with halogen -CC 3 -alkyloxy, straight-chain or branched
  • R 1 H; CC ⁇ alkyl; phenyl; CH 2 -phenyl, in which phenyl may optionally be substituted by halogen; CH 2 pyridinyl; tetrahydrofuranylmethyl
  • R 2 H, methyl, with the exception of the compound in which R is CH 2 phenyl and Ri is hydrogen.
  • Examples of compounds of general formula 1 are:
  • Tautomere is based on known 3-aminopyrazole-4-carboxylic acid esters (compounds of general formula 2) or 3-aminopyrazole-4-carboxamides (compounds of general formula 3) [P. Schmidt, J.
  • R 1 H, -CC 4 alkyl; phenyl; CH 2 -phenyl, in which phenyl may optionally be substituted by halogen; CH 2 pyridinyl; Tetrahydrofuranylmethyl mean and Et stands for an alkyl radical.
  • the compounds according to the invention as well as the compound 5-benzyl-2,5-dihydro-pyrazolo [3,4-d] pyrimidin-4-one already described or their pharmaceutically usable salts are suitable for the preparation of pharmaceutical compositions.
  • the pharmaceutical compositions or medicaments can contain one or more of the compounds according to the invention.
  • the usual pharmaceutical carriers and auxiliary substances can be used for the production of the pharmaceutical preparations.
  • the drugs can be administered parenterally (e.g. intravenously, intramuscularly, subcutaneously) or orally.
  • the application forms can be prepared by methods which are generally known and customary in pharmaceutical practice.
  • the compounds according to the invention have strong anticonvulsant effects, as does the compound 5-benzyl-2,5-dihydropyrazolo [3,4-d] pyrimidin-4-one already described.
  • the ED50 (po) was 18 mg in the rat in maximum electroshock / kg and the NT 50 > 500 mg / kg determined for neurotoxicity. This compound is also effective in cramp models with bicuculline and picrotoxin as the cramp-causing cause.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pain & Pain Management (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biomedical Technology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
EP01960709A 2000-08-26 2001-08-24 Antikonvulsiv wirkende 2,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one und verfahren zu deren darstellung Withdrawn EP1311510A1 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10042092 2000-08-26
DE10042092A DE10042092A1 (de) 2000-08-26 2000-08-26 Antikonvulsiv wirkende 2,5-Dihydro-pyrazolo(3,4-d)pyrimidin-4-one und Verfahren zu deren Darstellung
PCT/EP2001/009811 WO2002018387A1 (de) 2000-08-26 2001-08-24 Antikonvulsiv wirkende 2,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one und verfahren zu deren darstellung

Publications (1)

Publication Number Publication Date
EP1311510A1 true EP1311510A1 (de) 2003-05-21

Family

ID=7653967

Family Applications (1)

Application Number Title Priority Date Filing Date
EP01960709A Withdrawn EP1311510A1 (de) 2000-08-26 2001-08-24 Antikonvulsiv wirkende 2,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one und verfahren zu deren darstellung

Country Status (16)

Country Link
US (1) US20030186997A1 (ja)
EP (1) EP1311510A1 (ja)
JP (1) JP2004507547A (ja)
KR (1) KR20030036734A (ja)
CN (1) CN1449397A (ja)
AU (1) AU2001282124A1 (ja)
BG (1) BG107561A (ja)
BR (1) BR0113517A (ja)
CA (1) CA2420288A1 (ja)
DE (1) DE10042092A1 (ja)
EE (1) EE200300078A (ja)
HR (1) HRP20030226A2 (ja)
IL (1) IL154070A0 (ja)
NO (1) NO20030687L (ja)
RU (1) RU2003108258A (ja)
WO (1) WO2002018387A1 (ja)

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3165520A (en) * 1965-01-12 Certificate of correction
US3939161A (en) * 1973-10-29 1976-02-17 Abbott Laboratories 1,3-Dimethyl- 1H-pyrazolo(4,3-D) pyrimidine-7 (6H)-ones
US5763596A (en) * 1989-09-15 1998-06-09 Metabasis Therapeutics, Inc. C-4' modified adenosine kinase inhibitors
US5721356A (en) * 1989-09-15 1998-02-24 Gensia, Inc. Orally active adenosine kinase inhibitors
EP0729758A3 (en) * 1995-03-02 1997-10-29 Pfizer Pyrazolopyrimidines and pyrrolopyrimidines to treat neuronal disorders and other diseases
DE19827679A1 (de) * 1998-06-22 1999-12-23 Dresden Arzneimittel Adenosinrezeptoraffine, antikonvulsiv und antiallergisch/antiasthmatisch wirkende Pyrazolo[3,4-d]pyrimidine und Verfahren zu deren Herstellung

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0218387A1 *

Also Published As

Publication number Publication date
JP2004507547A (ja) 2004-03-11
WO2002018387A1 (de) 2002-03-07
IL154070A0 (en) 2003-07-31
US20030186997A1 (en) 2003-10-02
KR20030036734A (ko) 2003-05-09
NO20030687D0 (no) 2003-02-12
CN1449397A (zh) 2003-10-15
EE200300078A (et) 2004-12-15
NO20030687L (no) 2003-02-12
AU2001282124A1 (en) 2002-03-13
BG107561A (en) 2003-10-31
HRP20030226A2 (en) 2003-06-30
BR0113517A (pt) 2003-07-29
CA2420288A1 (en) 2002-03-07
RU2003108258A (ru) 2005-01-27
DE10042092A1 (de) 2002-03-07

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Free format text: 2,5-DIHYDRO-PYRAZOLO??3,4-D PYRIMIDIN-4-ONES WITH AN ANTICONVULSIVE ACTION AND METHODS FOR PRODUCING THE SAME