WO2009008769A1 - Oxalate n,n-diméthyl-2-n,n-diméthylaminométhylpyridyl-3-carbamate à activité anti-cholinestérase améliorant les fonctions cognitives - Google Patents

Oxalate n,n-diméthyl-2-n,n-diméthylaminométhylpyridyl-3-carbamate à activité anti-cholinestérase améliorant les fonctions cognitives Download PDF

Info

Publication number
WO2009008769A1
WO2009008769A1 PCT/RU2008/000393 RU2008000393W WO2009008769A1 WO 2009008769 A1 WO2009008769 A1 WO 2009008769A1 RU 2008000393 W RU2008000393 W RU 2008000393W WO 2009008769 A1 WO2009008769 A1 WO 2009008769A1
Authority
WO
WIPO (PCT)
Prior art keywords
amistigmine
dimethyl
dimethylaminomethylpyridyl
oxalate
rivastigmine
Prior art date
Application number
PCT/RU2008/000393
Other languages
English (en)
Russian (ru)
Inventor
Robert Georgievich Glushkov
Sergei Danilovich Juzhakov
Nataliya Ivanovna Andreeva
Evgeny Nikolaevich Salin
Larisa Nikolaevna Dronova
Svetlana Ivanovna Gavrilova
Valentina Vasilievna Asnina
Original Assignee
Obschestvo S Ogranishennoi Otvetstvennostu 'farmving'
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 Obschestvo S Ogranishennoi Otvetstvennostu 'farmving' filed Critical Obschestvo S Ogranishennoi Otvetstvennostu 'farmving'
Publication of WO2009008769A1 publication Critical patent/WO2009008769A1/fr

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
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/65—One oxygen atom attached in position 3 or 5
    • 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

Definitions

  • the invention relates to chemistry and medicine and relates to the preparation of a pharmaceutically acceptable oxalate N, N-dimethyl-2-N, N-dimethylaminomethylmethylpyridyl carbamate having anticholinesterase and antiamnestic properties.
  • aminostigmine dihydrochloride of this structure called aminostigmine is described as a compound with anticholinesterase activity / Prozorovsky V. B., Pavlova L. B., Panova P. A. et al.-Chem.-farm. Journal, 1991, Nl, 87-881 /, and also as a drug used in injectable dosage form as an antidote for poisoning with anticholinergic substances / Mashkovsky M. D. Medicines. Moscow, “The New Wave”. 2005, p. 202 /, but was not used to treat various dementias.
  • a significant disadvantage of aminostigmine is hygroscopicity, which greatly complicates its standardization and complicates the production of dosage forms.
  • An object of the present invention is to provide a pharmaceutically acceptable potential drug of the 3-oxipyridine series with anticholinesterase activity and the ability to improve cognitive function. It should be emphasized that in order to solve this problem, a large group of N, N-dimethyl-2-N, N-dimethylaminomethylmethylpyridyl-3-carbamate salts with various organic and inorganic acids was synthesized, and only 2 N, N-dimethyl-2-N oxalate , N-dimethylaminomethylpyridyl-3-carbamate (I) did not show hygroscopic properties.
  • Compound I is prepared by reacting N, N-dimethyl-2-N, N-dimethylaminomethylmethylpyridyl-3-carbamate / Johp A., Aeschlimarm, Arthur Stemrel, Pat. US 2.512.732, Jupe 27.1950; Chem. Abstr., V. 44, N 19-20, p. 8961-8962 (1950) / with oxalic acid in an organic solvent, for example acetone. Structure I is confirmed by elemental analysis, PMR and mass spectra. Example.
  • mice that received electroshock after training (without administering the studied drugs), a significant deterioration in conditioned reflex activity was noted, which is manifested by a 3-fold decrease in the latent period of entry into the dark compartment of the chamber.
  • the introduction of amistigmine, as well as rivastigmine (excelon) leads to a dose-dependent significant weakening of the amnestic effect of electroshock (the latent period increases by more than 2 times) (right column, table 6).
  • the claimed compound in anticholinesterase activity and in the ability to improve cognitive function is superior to the rivastigmine (excelon) drug used in clinical practice for the treatment of dementia, and therefore it is of interest as a potential antiamnestic agent.
  • Table 1 the claimed compound (amistigmine) in anticholinesterase activity and in the ability to improve cognitive function is superior to the rivastigmine (excelon) drug used in clinical practice for the treatment of dementia, and therefore it is of interest as a potential antiamnestic agent.

Abstract

La présente invention relève du domaine de la chimie et de la médecine et concerne en particulier la production d'oxalate N,N-diméthyl-2-N,N-diméthylaminométhylpyridyl-3-carbamate pharmaceutiquement acceptable qui présente une activité anti-cholinestérase et anti-amnésique et qui, à la différence d'autres sels de cette structure, n'est pas un composé hygroscopique. Le fait que le composé de cette invention présente une activité anti-cholinestérase supérieure à celle de la rivastigmine (exelon) permet de le considérer comme agent thérapeutique potentiel pour le traitement de diverses déficiences mentales.
PCT/RU2008/000393 2007-07-09 2008-06-25 Oxalate n,n-diméthyl-2-n,n-diméthylaminométhylpyridyl-3-carbamate à activité anti-cholinestérase améliorant les fonctions cognitives WO2009008769A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
RU2007125609/04A RU2339620C1 (ru) 2007-07-09 2007-07-09 Оксалат n, n-диметил-2-n, n-диметиламинометилпиридил-3-карбамат, обладающий антихолинэстеразной активностью и способностью улучшать когнитивные функции
RU2007125609 2007-07-09

Publications (1)

Publication Number Publication Date
WO2009008769A1 true WO2009008769A1 (fr) 2009-01-15

Family

ID=40193147

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/RU2008/000393 WO2009008769A1 (fr) 2007-07-09 2008-06-25 Oxalate n,n-diméthyl-2-n,n-diméthylaminométhylpyridyl-3-carbamate à activité anti-cholinestérase améliorant les fonctions cognitives

Country Status (2)

Country Link
RU (1) RU2339620C1 (fr)
WO (1) WO2009008769A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011100373A1 (fr) 2010-02-09 2011-08-18 The Johns Hopkins University Procédés et compositions pour améliorer la fonction cognitive
WO2014144801A1 (fr) 2013-03-15 2014-09-18 Agenebio Inc. Procédés et compositions pour améliorer la fonction cognitive
US10154988B2 (en) 2012-11-14 2018-12-18 The Johns Hopkins University Methods and compositions for treating schizophrenia
US10159648B2 (en) 2015-05-22 2018-12-25 Agenebio, Inc. Extended release pharmaceutical compositions of levetiracetam
US10806717B2 (en) 2013-03-15 2020-10-20 The Johns Hopkins University Methods and compositions for improving cognitive function

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2451513C1 (ru) * 2010-12-27 2012-05-27 Федеральное государственное унитарное предприятие Научно-производственный центр "Фармзащита" Федерального медико-биологического агентства" Способ получения n,n-диметил-(2-n1,n1-диметиламинометилпиридил-3)карбамата или его солей

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2512732A (en) * 1948-05-14 1950-06-27 Hoffmann La Roche Carbamic acid esters of (3-hydroxy-2-pyridylmethyl) amines and salts thereof
RU1767843C (ru) * 1990-06-15 1995-05-27 Научно-исследовательский институт военной медицины Способ получения биологически активного вещества на основе соли n,n-диметил-(2-n`,n`-диметиламинометилпиридил-3)карбамата и стиролвинилбензольного сульфокатионита, обладающего свойством ингибировать холинэстеразы

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2512732A (en) * 1948-05-14 1950-06-27 Hoffmann La Roche Carbamic acid esters of (3-hydroxy-2-pyridylmethyl) amines and salts thereof
RU1767843C (ru) * 1990-06-15 1995-05-27 Научно-исследовательский институт военной медицины Способ получения биологически активного вещества на основе соли n,n-диметил-(2-n`,n`-диметиламинометилпиридил-3)карбамата и стиролвинилбензольного сульфокатионита, обладающего свойством ингибировать холинэстеразы

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011100373A1 (fr) 2010-02-09 2011-08-18 The Johns Hopkins University Procédés et compositions pour améliorer la fonction cognitive
US10154988B2 (en) 2012-11-14 2018-12-18 The Johns Hopkins University Methods and compositions for treating schizophrenia
US10624875B2 (en) 2012-11-14 2020-04-21 The Johns Hopkins University Methods and compositions for treating schizophrenia
WO2014144801A1 (fr) 2013-03-15 2014-09-18 Agenebio Inc. Procédés et compositions pour améliorer la fonction cognitive
US10806717B2 (en) 2013-03-15 2020-10-20 The Johns Hopkins University Methods and compositions for improving cognitive function
US11160785B2 (en) 2013-03-15 2021-11-02 Agenebio Inc. Methods and compositions for improving cognitive function
US10159648B2 (en) 2015-05-22 2018-12-25 Agenebio, Inc. Extended release pharmaceutical compositions of levetiracetam
US10925834B2 (en) 2015-05-22 2021-02-23 Agenebio, Inc. Extended release pharmaceutical compositions of levetiracetam

Also Published As

Publication number Publication date
RU2339620C1 (ru) 2008-11-27

Similar Documents

Publication Publication Date Title
WO2009008769A1 (fr) Oxalate n,n-diméthyl-2-n,n-diméthylaminométhylpyridyl-3-carbamate à activité anti-cholinestérase améliorant les fonctions cognitives
US4757072A (en) Carcinostatic agent
BR112016030968B1 (pt) Análogos de pridopidina, preparação e uso destes
EP0022958A1 (fr) Dérivés d'urée pour utilisation dans le traitement des troubles du métabolisme des matières grasses
CZ177596A3 (en) 2,4-disulfonylphenylbutylnitrone, salts thereof and the use of the salts as medicaments
EP0530446A2 (fr) Utilisation d'acides carboxyliques soufrés pour combattre les agents excicateurs d'origine physiopathologique et les maladies en résultant ainsi que les maladies allergiques, et leur préparation en tant que médicament
EP2994457B1 (fr) Formulations pharmaceutiques d'atténuation de rayonnements
EP1467994A1 (fr) Derives de pteridine, procede de production de ces derives et leur utilisation
WO2014116642A1 (fr) Dimères de trioxane dérivés d'artémisinine liés à deux atomes de carbone
EP0432856A2 (fr) Utilisation du rolipram pour traiter la démence
CN114028406A (zh) 阿尔茨海默疾病或痴呆预防、治疗或拖延用药学组合物
CN107936008B (zh) 氘代化合物及其医药用途
DE2625222B2 (de) 13-Dithiacyclopentan-2-ylidenmalonsäureester, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel
CN109761945B (zh) 一种柚皮素-o-烷基胺类化合物、制备方法和应用
DE102005009909A1 (de) Verbindungen geeignet zur Beseitigung fehlgefalteter Proteine
JP7295145B2 (ja) 神経変性疾患を治療するための医薬及びその使用
EP0369286A2 (fr) Dérivés de la dibenzazépine pour le traitement de maladies aigues et chroniques des voies respiratoires
WO2002022578A1 (fr) Derives de (2-azabicyclo[2.2.1]hept-7-yl)methanol utilises comme angonistes du recepteur de l'acetylcholine nicotinique
DE2625220B2 (de) Arzneimittel zur Behandlung von Leberkrankheiten
CN107434799B (zh) 一种2-氨基-3-取代巯基丙酸酯衍生物，制备方法及其应用
DE2213028B2 (de) Dl-3-formylaminothiacyclopentan-2- on-, verfahren zu dessen herstellung und dl-3-formylamino-thiacyclopentan-2-on und andere acylderivate enthaltende pharmazeutische zusammensetzungen
US20200392126A1 (en) Isoxazolyl compounds as receptor modulating compounds and methods and uses thereof
JP3681770B2 (ja) 老年性痴呆症又はアルツハイマー病治療剤
RU2665970C1 (ru) Средство для коррекции холинергических нарушений мнестических процессов
DE19941540C2 (de) Sulfonylcarboxamide zur Herstellung von Medikamenten zur Prophylaxe oder Behandlung von Hyperlipidämie

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 08779212

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 08779212

Country of ref document: EP

Kind code of ref document: A1