BE779775A - DERIVATIVES OF UREA, METHOD FOR PREPARING THEM AND THEIR APPLICATIONS - Google Patents

DERIVATIVES OF UREA, METHOD FOR PREPARING THEM AND THEIR APPLICATIONS

Info

Publication number
BE779775A
BE779775A BE779775A BE779775A BE779775A BE 779775 A BE779775 A BE 779775A BE 779775 A BE779775 A BE 779775A BE 779775 A BE779775 A BE 779775A BE 779775 A BE779775 A BE 779775A
Authority
BE
Belgium
Prior art keywords
emi
group
atom
solution
urea
Prior art date
Application number
BE779775A
Other languages
French (fr)
Original Assignee
Smith Kline French Lab
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=26240626&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=BE779775(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority claimed from GB635271A external-priority patent/GB1338169A/en
Application filed by Smith Kline French Lab filed Critical Smith Kline French Lab
Publication of BE779775A publication Critical patent/BE779775A/en

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
    • C07D213/70—Sulfur atoms
    • 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
    • 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
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/32—Sulfur 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
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/65—One oxygen atom attached in position 3 or 5
    • 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
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members 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
    • C07D233/84—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
    • C07D249/12—Oxygen or sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
    • C07D263/46—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
    • C07D277/36—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
    • C07D285/01—Five-membered rings
    • C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
    • C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
    • C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
    • C07D285/125—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
    • C07D285/135—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Handcart (AREA)

Description

       

   <EMI ID=1.1> 

  
des procédés pour leur préparation. Les composés suivant l'invention peuvent se présenter sous forme de sels d'addition" mais

  
 <EMI ID=2.1> 

  
Une hypothèse depuis longtemps admise est que beaucoup

  
des substances à activité physiologique se combinent dans le

  
 <EMI ID=3.1> 

  
 <EMI ID=4.1> 

  
mais .comme ses activités sont de plusieurs genres, l'on suppose 

  
qu'il existe plusieurs types de récepteurs d'histamine. Le genre

  
 <EMI ID=5.1> 

  
 <EMI ID=6.1> 

  
le fait qu'ils agissent comme récepteurs d'histamine d'une autre

  
 <EMI ID=7.1> 

  
les composés'faisant l'objet de l'invention peuvent être représentés par la formule. générale ci-après ? étant entendu que

  
 <EMI ID=8.1> 

  
 <EMI ID=9.1> 

  

 <EMI ID=10.1> 


  
 <EMI ID=11.1>   <EMI ID=12.1> 

  
le, bensyle, un atome d'halogène, un groupe amino ou un groupe <EMI ID=13.1> 

  
du groupe A un autre noyau, par exemple un noyau.benzène ou pyrimidine, ou un noyau partiellement insaturé ; 1 et m sont des nom-

  
 <EMI ID=14.1> 

  
un groupe nitro ou cyano. Le groupe A est de -préférence choisi de manière que l'atome d'azote soit adjacent à l'atome de carbone indique et,. mieux encore;qu'il forme avec cet atome de carbone un

  
 <EMI ID=15.1> 

  
 <EMI ID=16.1>   <EMI ID=17.1> 

  
préparés à partir de composés de la formule générale 

  

 <EMI ID=18.1> 


  
 <EMI ID=19.1> 

  
 <EMI ID=20.1> 

  

 <EMI ID=21.1> 


  
 <EMI ID=22.1> 

  
 <EMI ID=23.1> 

  
méthoxy. Le premier stade de cette préparation consiste à faire

  
 <EMI ID=24.1> 

  

 <EMI ID=25.1> 


  
 <EMI ID=26.1> 

  
Lorsque Q est un halogène, cette réaction peut être ef-  fectuée dans des conditions fortement basiques, par exemple en présence d'éthoxyde de sodium ou d'hydroxyde de sodium. Puisque le composé de la formule III est uns amine primaire, il est nécessaire de protéger le groupe amino, par exemple par un groupe  phtal-imido, qui peut ensuite être séparé par hydrolyse acide ou

  
 <EMI ID=27.1> 

  
la réaction s'effectue dans des conditions acides, par exemple en présence d'un acide halohydrique, tel qu'une solution aqueuse à

  
 <EMI ID=28.1> 

  
l'acide acétique glacial. Lorsque Q est un radical méthoxy, la réaction peut également s'effectuer en présence d'une solution  <EMI ID=29.1> 

  
Les produits obtenus par les procédés si-dessus sont des composés de la formule suivante , ou encore les sels d'addition .

  
 <EMI ID=30.1> 

  

 <EMI ID=31.1> 


  
 <EMI ID=32.1> 

  
3.' on fait réagir dans un solvant approprié, tel que le chloroforme, avec, un isothiocyanate d'acyle. Une hydrolysa alcaline du 

  
 <EMI ID=33.1> 

  
 <EMI ID=34.1> 

  
me d'hydrogène et Y et E -sont des atomes de soufre: peuvent également être préparésdirectement par la réaction à température

  
 <EMI ID=35.1> 

  
nium ou d'un métal tel que le sodium ou le potassium. 

  
 <EMI ID=36.1>   <EMI ID=37.1> 

  

 <EMI ID=38.1> 


  
 <EMI ID=39.1> 

  
 <EMI ID=40.1> 

  
 <EMI ID=41.1> 

  

 <EMI ID=42.1> 


  
 <EMI ID=43.1>   <EMI ID=44.1> 

  

 <EMI ID=45.1> 


  
Les composés de la formule VII peuvent être transformés en des 

  
 <EMI ID=46.1> 

  
décrites ci-dessus pour la transformation des composés de la for-

  
 <EMI ID=47.1> 

  
 <EMI ID=48.1> 

  
Les composés de la formule 1, pour lesquels Y est un

  
 <EMI ID=49.1> 

  
nière semblable au départ d'un composé de la formule : 

  

 <EMI ID=50.1> 


  
 <EMI ID=51.1> 

  

 <EMI ID=52.1> 


  
 <EMI ID=53.1>  
 <EMI ID=54.1> 
 <EMI ID=55.1>  tant qu'inhibiteurs de certaines actions de l'histamine,qui ne

  
 <EMI ID=56.1> 

  
ne"- C'est ainsi que l'on a constaté qu'ils inhibent sélectivement la sécrétion de l'acide ; gastrique, -stimulée par l'histamine,

  
 <EMI ID=57.1> 

  
ventricule droit isolé de cobaye et l'utérus isolé du rat. les

  
 <EMI ID=58.1> 

  
un aliment..' .

  
Le taux d'activité de. compositions' contenant les dérivés <EMI ID=59.1> 

  
tration sous forme d'une composition pharmaceutique, qui contient:
comme ingrédient actif essentiel, ou comme ]:'un- de ses ingrédients - 

  
 <EMI ID=60.1> 

  
 <EMI ID=61.1> 

  
de comprimés , en capsules, en solution injectable ou comme crème   <EMI ID=62.1> 

  
pour des applications locales. "$la

  
1" invention est décrite si-après plus en détail à l'aide

  
 <EMI ID=63.1>  on refroidit la solution jaune obtenue sur un bain de sel et de glacé. puis on ajoute goutte à goutte, en l'espace de 10 minutes, 

  
 <EMI ID=64.1> 

  
té par addition d'eau et séparé par filtration" Le filtrat est .concentré et alcalinisé avec une solution aqueuse, de bicarbonate <EMI ID=65.1>   <EMI ID=66.1>  lendemain à la température ordinaire), puis filtré et le filtrat acidifié avec de l'acide chlorhydrique concentré. La 'solution est ensuite évaporée à siccité et au résidu dissous dans l'étha-

  
 <EMI ID=67.1> 

  
 <EMI ID=68.1> 

  
traite par l'alcool isopropyliquep pour la séparer des produits  inorganiques,et les extraits sont concentrés jusque environ 70

  
 <EMI ID=69.1> 

  
froidissement évaporé à siccité. S'imite résiduelle est dissoute

  
 <EMI ID=70.1>   <EMI ID=71.1>  
 <EMI ID=72.1> 
 <EMI ID=73.1> 

  
 <EMI ID=74.1> 

  
 <EMI ID=75.1> 

  
méthyle dans des conditions semblables à celles décrites dans .

  
 <EMI ID=76.1> 

  
 <EMI ID=77.1> 

  
 <EMI ID=78.1>  <EMI ID=79.1> 

  
 <EMI ID=80.1>   <EMI ID=81.1> 

  
vie d'une agitation de 3 heures à la température ambiante'- on a-

  
 <EMI ID=82.1> 

  
 <EMI ID=83.1> 

  
hydrogéné à la température ordinaire et à la pression atmosphérique jusqu'à absorption de la quantité théorique d'hydrogène,, Après filtration du mélange, le filtrat est concentré et par ad-

  
 <EMI ID=84.1>   <EMI ID=85.1> 

  
g) avec le nitrite de sodium, suivie de la réduction du 2-oximino-3-oxo-4-phényl-butyrate d'éthyle brut (10,8 g), comme décrit

  
 <EMI ID=86.1> 

  
En suivant le mode opératoire du chapitre (b) précé-

  
 <EMI ID=87.1> 

  
 <EMI ID=88.1>   <EMI ID=89.1> 

  
obtient un solide, qui est recueilli après concentration par-  tielle et donne par recristallisation, dans l'acétate d'éthyle la

  
 <EMI ID=90.1>  
 <EMI ID=91.1> 
 pour laquelle le tableau II indique les diverses significations

  
 <EMI ID=92.1> 

  

 <EMI ID=93.1> 


  
 <EMI ID=94.1> 

  
sous atmosphère d'azote. Après addition complète, la solution

  
 <EMI ID=95.1> 

  
 <EMI ID=96.1> 

  
tente de quelques gouttes de la solution d'hydroxyde de potas-

  
 <EMI ID=97.1>   <EMI ID=98.1>  <EMI ID=99.1> 

  
 <EMI ID=100.1> 

  
 <EMI ID=101.1> 

  
On maintient la solution à cette température pendant 1 heure, _ 

  
 <EMI ID=102.1>   <EMI ID=103.1> 

  
mélange alcool isopropylique-acétate d'éthyle-éther). Par recris-

  
 <EMI ID=104.1>   <EMI ID=105.1> 

  
 <EMI ID=106.1> 

  
 <EMI ID=107.1> 

  
 <EMI ID=108.1>  <EMI ID=109.1> 

  
tenir après évaporation du mélange réactionnel un solide jaune

  
 <EMI ID=110.1> 

  
 <EMI ID=111.1> 

  
 <EMI ID=112.1>  

  

 <EMI ID=113.1> 


  
 <EMI ID=114.1> 

  
! noyau, le solvant employé pour la recristallisation du produit,

  
 <EMI ID=115.1> 

  
 <EMI ID=116.1> 

  
 <EMI ID=117.1> 

  
(i) En agitant, on ajoute de l'acide chlorhydrique (90 ml)

  
 <EMI ID=118.1> 

  
séparation des produits inorganiques par filtration, on ajoute

  
 <EMI ID=119.1> 

  
heures, à reflux. Par concentration et refroidissement, on obtient un solide blanc,.qui par recristallisation dans l'éthanol

  
 <EMI ID=120.1> 

  
propyle (13,4 g), on chauffe la solution obtenue à reflux pendant 2,5 heures, puis on concentre sous pression réduite. -le

  
 <EMI ID=121.1> 

  
(iii) A une solution de 2-(3-phtalimido-propylthio)-oxazole
(10 g) dans l'éthanol (173 ml), maintenue en agitation* on ajou-

  
 <EMI ID=122.1> 

  
chauffe la solution à reflux pendant 25 minutes. Après refroidissement, on sépare l'hydraside phtalique par filtration, on

  
 <EMI ID=123.1> 

  
 <EMI ID=124.1> 

  
pylthio)-oxazole brut, qui est lavé deux fois à l'éther et disvous dans l'éthanol (60 ml). Après addition d'isothiocyanate de méthyle (2,54 g), la solution est chauffée à reflux pendant 30

  
 <EMI ID=125.1> 

  
 <EMI ID=126.1>   <EMI ID=127.1> 

  
(ii) Le traitement du dérivé de phtalimide ci-dessus,' (3 "0

  
 <EMI ID=128.1> 

  
 <EMI ID=129.1> 

  
 <EMI ID=130.1> 

  
 <EMI ID=131.1> 

  
 <EMI ID=132.1> 

  
 <EMI ID=133.1> 

  
produit est ensuite alcalinisé.par du carbonate de potassium

  
 <EMI ID=134.1> 

  
l'alcool isopropylique (3 x 50 ml). La concentration des ex-:- 

  
 <EMI ID=135.1>   <EMI ID=136.1> 

  
purifié par chromatographie sur une colonne de gel de Milice,

  
 <EMI ID=137.1> 

  
d'alumine, avec le chloroforme comme éluant. Après recristallisa-

  
 <EMI ID=138.1>   <EMI ID=139.1> 

  
dans de l'eau (50 ml) est chauffée à reflux pendant 3 heures.',  Âpres concentration à faible volume et acidification par de l'a-

  
 <EMI ID=140.1> 

  
dans le méthanol (35 ml) est chauffée pendant 2,5 heures entre
50 et 60[deg.]0 et puis laissée au repos.à la température ordinaire pendant 48 heures. Le produit cristallisé est séparé par filtra-

  
 <EMI ID=141.1> 

  
 <EMI ID=142.1>   <EMI ID=143.1>  
 <EMI ID=144.1> 
 <EMI ID=145.1> 
 
 <EMI ID=146.1> 
 <EMI ID=147.1> 
 
 <EMI ID=148.1> 
 <EMI ID=149.1> 
 
 <EMI ID=150.1> 
 <EMI ID=151.1> 
 
 <EMI ID=152.1> 
 <EMI ID=153.1> 
 
 <EMI ID=154.1> 
 <EMI ID=155.1> 
 
 <EMI ID=156.1> 
 <EMI ID=157.1> 
 
 <EMI ID=158.1> 
 <EMI ID=159.1> 
 
 <EMI ID=160.1> 
 <EMI ID=161.1> 
 
 <EMI ID=162.1> 
 <EMI ID=163.1> 
 
 <EMI ID=164.1> 
 <EMI ID=165.1> 
 
 <EMI ID=166.1> 
 <EMI ID=167.1> 
 
 <EMI ID=168.1> 
 <EMI ID=169.1> 
 
 <EMI ID=170.1> 
 <EMI ID=171.1> 
 
 <EMI ID=172.1> 
 <EMI ID=173.1> 
 
 <EMI ID=174.1> 
 <EMI ID=175.1> 
  <EMI ID=176.1> 

  

 <EMI ID=177.1> 


  
dans laquelle le symbole A désigne un groupe qui forme avec l'atome de carbone indiqué un noyau hétérocyclique non saturée qui contient au moins un atome d'azote et peut comporter d'autres  hétéro-atomes, comme le soufre et l'oxygène j les symboles X et. qui peuvent être identiques ou différents, désignent chacun un atome d'hydrogène, un radical alcoyle inférieur, trifluoro-

  
 <EMI ID=178.1> 

  
groupe

  

 <EMI ID=179.1> 


  
 <EMI ID=180.1> 

  
 <EMI ID=181.1> 

  
 <EMI ID=182.1> 

  
symbole Y désigne un atome d'oxygène ou de soufre ou un groupe

  
 <EMI ID=183.1> 

  
groupe A ferme un noyau autre qu'un noyau pyridine, un groupe

  
 <EMI ID=184.1> 

  
 <EMI ID=185.1> 

  
 <EMI ID=186.1> 

  
d'hydrogène, ; un groupe nitro ou cyano.



   <EMI ID = 1.1>

  
processes for their preparation. The compounds according to the invention can be provided in the form of addition salts "but

  
 <EMI ID = 2.1>

  
A long-accepted hypothesis is that many

  
substances with physiological activity combine in the

  
 <EMI ID = 3.1>

  
 <EMI ID = 4.1>

  
but since its activities are of several kinds, it is assumed

  
that there are several types of histamine receptors. Genre

  
 <EMI ID = 5.1>

  
 <EMI ID = 6.1>

  
the fact that they act as histamine receptors of another

  
 <EMI ID = 7.1>

  
the compounds forming the object of the invention can be represented by the formula. general below? Being heard that

  
 <EMI ID = 8.1>

  
 <EMI ID = 9.1>

  

 <EMI ID = 10.1>


  
 <EMI ID = 11.1> <EMI ID = 12.1>

  
le, bensyl, a halogen atom, an amino group or a group <EMI ID = 13.1>

  
from group A another ring, for example a benzene or pyrimidine ring, or a partially unsaturated ring; 1 and m are nouns

  
 <EMI ID = 14.1>

  
a nitro or cyano group. The group A is preferably chosen such that the nitrogen atom is adjacent to the carbon atom indicates and ,. better still; that it forms with this carbon atom a

  
 <EMI ID = 15.1>

  
 <EMI ID = 16.1> <EMI ID = 17.1>

  
prepared from compounds of the general formula

  

 <EMI ID = 18.1>


  
 <EMI ID = 19.1>

  
 <EMI ID = 20.1>

  

 <EMI ID = 21.1>


  
 <EMI ID = 22.1>

  
 <EMI ID = 23.1>

  
methoxy. The first stage of this preparation is to make

  
 <EMI ID = 24.1>

  

 <EMI ID = 25.1>


  
 <EMI ID = 26.1>

  
When Q is halogen, this reaction can be carried out under strongly basic conditions, for example in the presence of sodium ethoxide or sodium hydroxide. Since the compound of formula III is a primary amine, it is necessary to protect the amino group, for example by a phthalimido group, which can then be separated by acid hydrolysis or

  
 <EMI ID = 27.1>

  
the reaction is carried out under acidic conditions, for example in the presence of a hydrohalic acid, such as an aqueous solution in

  
 <EMI ID = 28.1>

  
glacial acetic acid. When Q is a methoxy radical, the reaction can also be carried out in the presence of a solution <EMI ID = 29.1>

  
The products obtained by the above processes are compounds of the following formula, or else the addition salts.

  
 <EMI ID = 30.1>

  

 <EMI ID = 31.1>


  
 <EMI ID = 32.1>

  
3. ' reacting in a suitable solvent, such as chloroform, with an acyl isothiocyanate. An alkaline hydrolysis of

  
 <EMI ID = 33.1>

  
 <EMI ID = 34.1>

  
me of hydrogen and Y and E - are sulfur atoms: can also be prepared directly by reaction at temperature

  
 <EMI ID = 35.1>

  
nium or a metal such as sodium or potassium.

  
 <EMI ID = 36.1> <EMI ID = 37.1>

  

 <EMI ID = 38.1>


  
 <EMI ID = 39.1>

  
 <EMI ID = 40.1>

  
 <EMI ID = 41.1>

  

 <EMI ID = 42.1>


  
 <EMI ID = 43.1> <EMI ID = 44.1>

  

 <EMI ID = 45.1>


  
Compounds of formula VII can be converted into

  
 <EMI ID = 46.1>

  
described above for the transformation of the compounds of the

  
 <EMI ID = 47.1>

  
 <EMI ID = 48.1>

  
The compounds of formula 1, for which Y is a

  
 <EMI ID = 49.1>

  
similar starting point for a compound of the formula:

  

 <EMI ID = 50.1>


  
 <EMI ID = 51.1>

  

 <EMI ID = 52.1>


  
 <EMI ID = 53.1>
 <EMI ID = 54.1>
 <EMI ID = 55.1> as inhibitors of certain actions of histamine, which

  
 <EMI ID = 56.1>

  
ne "- Thus it was found that they selectively inhibit the secretion of gastric acid, -stimulated by histamine,

  
 <EMI ID = 57.1>

  
isolated right ventricle of guinea pig and isolated uterus of rat. the

  
 <EMI ID = 58.1>

  
food .. '.

  
The activity rate of. compositions' containing the derivatives <EMI ID = 59.1>

  
tration in the form of a pharmaceutical composition, which contains:
as an essential active ingredient, or as]: 'one of its ingredients -

  
 <EMI ID = 60.1>

  
 <EMI ID = 61.1>

  
tablets, capsules, solution for injection or as a cream <EMI ID = 62.1>

  
for local applications. "$ the

  
1 "invention is described hereinafter in more detail using

  
 <EMI ID = 63.1> the yellow solution obtained is cooled on a salt and ice bath. then add dropwise, over 10 minutes,

  
 <EMI ID = 64.1>

  
ted by adding water and separated by filtration "The filtrate is concentrated and basified with an aqueous solution of bicarbonate <EMI ID = 65.1> <EMI ID = 66.1> the next day at room temperature), then filtered and the filtrate acidified with concentrated hydrochloric acid The solution is then evaporated to dryness and to the residue dissolved in ethanol.

  
 <EMI ID = 67.1>

  
 <EMI ID = 68.1>

  
treated with isopropyl alcohol to separate it from inorganic products, and extracts are concentrated to about 70

  
 <EMI ID = 69.1>

  
cooling evaporated to dryness. Residual imitates are dissolved

  
 <EMI ID = 70.1> <EMI ID = 71.1>
 <EMI ID = 72.1>
 <EMI ID = 73.1>

  
 <EMI ID = 74.1>

  
 <EMI ID = 75.1>

  
methyl under conditions similar to those described in.

  
 <EMI ID = 76.1>

  
 <EMI ID = 77.1>

  
 <EMI ID = 78.1> <EMI ID = 79.1>

  
 <EMI ID = 80.1> <EMI ID = 81.1>

  
life of stirring for 3 hours at room temperature '- we have

  
 <EMI ID = 82.1>

  
 <EMI ID = 83.1>

  
hydrogenated at room temperature and at atmospheric pressure until the theoretical quantity of hydrogen has been absorbed, After filtration of the mixture, the filtrate is concentrated and by adding

  
 <EMI ID = 84.1> <EMI ID = 85.1>

  
g) with sodium nitrite, followed by reduction of crude ethyl 2-oximino-3-oxo-4-phenyl-butyrate (10.8 g), as described

  
 <EMI ID = 86.1>

  
By following the procedure in chapter (b) above

  
 <EMI ID = 87.1>

  
 <EMI ID = 88.1> <EMI ID = 89.1>

  
obtains a solid, which is collected after partial concentration and gives by recrystallization, in ethyl acetate the

  
 <EMI ID = 90.1>
 <EMI ID = 91.1>
 for which Table II indicates the various meanings

  
 <EMI ID = 92.1>

  

 <EMI ID = 93.1>


  
 <EMI ID = 94.1>

  
under a nitrogen atmosphere. After complete addition, the solution

  
 <EMI ID = 95.1>

  
 <EMI ID = 96.1>

  
try a few drops of the potassium hydroxide solution

  
 <EMI ID = 97.1> <EMI ID = 98.1> <EMI ID = 99.1>

  
 <EMI ID = 100.1>

  
 <EMI ID = 101.1>

  
The solution is maintained at this temperature for 1 hour, _

  
 <EMI ID = 102.1> <EMI ID = 103.1>

  
isopropyl alcohol-ethyl acetate-ether mixture). By recris-

  
 <EMI ID = 104.1> <EMI ID = 105.1>

  
 <EMI ID = 106.1>

  
 <EMI ID = 107.1>

  
 <EMI ID = 108.1> <EMI ID = 109.1>

  
after evaporation of the reaction mixture hold a yellow solid

  
 <EMI ID = 110.1>

  
 <EMI ID = 111.1>

  
 <EMI ID = 112.1>

  

 <EMI ID = 113.1>


  
 <EMI ID = 114.1>

  
! core, the solvent used for recrystallization of the product,

  
 <EMI ID = 115.1>

  
 <EMI ID = 116.1>

  
 <EMI ID = 117.1>

  
(i) With stirring, hydrochloric acid (90 ml) is added

  
 <EMI ID = 118.1>

  
separation of inorganic products by filtration, one adds

  
 <EMI ID = 119.1>

  
hours, at reflux. By concentration and cooling, a white solid is obtained, which by recrystallization from ethanol

  
 <EMI ID = 120.1>

  
propyl (13.4 g), the resulting solution is heated at reflux for 2.5 hours, then concentrated under reduced pressure. -the

  
 <EMI ID = 121.1>

  
(iii) To a solution of 2- (3-phthalimido-propylthio) -oxazole
(10 g) in ethanol (173 ml), kept stirring * we add

  
 <EMI ID = 122.1>

  
heat the solution to reflux for 25 minutes. After cooling, the phthalic hydraside is separated by filtration,

  
 <EMI ID = 123.1>

  
 <EMI ID = 124.1>

  
crude pylthio) -oxazole, which is washed twice with ether and dissolved in ethanol (60 ml). After addition of methyl isothiocyanate (2.54 g), the solution is heated under reflux for 30

  
 <EMI ID = 125.1>

  
 <EMI ID = 126.1> <EMI ID = 127.1>

  
(ii) The treatment of the above phthalimide derivative, '(3 "0

  
 <EMI ID = 128.1>

  
 <EMI ID = 129.1>

  
 <EMI ID = 130.1>

  
 <EMI ID = 131.1>

  
 <EMI ID = 132.1>

  
 <EMI ID = 133.1>

  
product is then alkalized by potassium carbonate

  
 <EMI ID = 134.1>

  
isopropyl alcohol (3 x 50 ml). The concentration of ex -: -

  
 <EMI ID = 135.1> <EMI ID = 136.1>

  
purified by chromatography on a column of Militia gel,

  
 <EMI ID = 137.1>

  
of alumina, with chloroform as eluent. After recrystallization

  
 <EMI ID = 138.1> <EMI ID = 139.1>

  
in water (50 ml) is heated under reflux for 3 hours. After concentration to low volume and acidification with a-

  
 <EMI ID = 140.1>

  
in methanol (35 ml) is heated for 2.5 hours between
50 and 60 [deg.] 0 and then left to stand at room temperature for 48 hours. The crystallized product is separated by filtration.

  
 <EMI ID = 141.1>

  
 <EMI ID = 142.1> <EMI ID = 143.1>
 <EMI ID = 144.1>
 <EMI ID = 145.1>
 
 <EMI ID = 146.1>
 <EMI ID = 147.1>
 
 <EMI ID = 148.1>
 <EMI ID = 149.1>
 
 <EMI ID = 150.1>
 <EMI ID = 151.1>
 
 <EMI ID = 152.1>
 <EMI ID = 153.1>
 
 <EMI ID = 154.1>
 <EMI ID = 155.1>
 
 <EMI ID = 156.1>
 <EMI ID = 157.1>
 
 <EMI ID = 158.1>
 <EMI ID = 159.1>
 
 <EMI ID = 160.1>
 <EMI ID = 161.1>
 
 <EMI ID = 162.1>
 <EMI ID = 163.1>
 
 <EMI ID = 164.1>
 <EMI ID = 165.1>
 
 <EMI ID = 166.1>
 <EMI ID = 167.1>
 
 <EMI ID = 168.1>
 <EMI ID = 169.1>
 
 <EMI ID = 170.1>
 <EMI ID = 171.1>
 
 <EMI ID = 172.1>
 <EMI ID = 173.1>
 
 <EMI ID = 174.1>
 <EMI ID = 175.1>
  <EMI ID = 176.1>

  

 <EMI ID = 177.1>


  
in which the symbol A denotes a group which forms with the indicated carbon atom an unsaturated heterocyclic ring which contains at least one nitrogen atom and may contain other hetero atoms, such as sulfur and oxygen; X and symbols. which may be identical or different, each denote a hydrogen atom, a lower alkyl radical, trifluoro-

  
 <EMI ID = 178.1>

  
group

  

 <EMI ID = 179.1>


  
 <EMI ID = 180.1>

  
 <EMI ID = 181.1>

  
 <EMI ID = 182.1>

  
symbol Y denotes an oxygen or sulfur atom or a group

  
 <EMI ID = 183.1>

  
group A closes a nucleus other than a pyridine nucleus, a group

  
 <EMI ID = 184.1>

  
 <EMI ID = 185.1>

  
 <EMI ID = 186.1>

  
hydrogen,; a nitro or cyano group.

Claims (1)

2;- Composé suivant la revendication 1, caractérisé en ce que le noyau hétérocyclique non saturé de base contient <EMI ID=187.1> 2; - A compound according to claim 1, characterized in that the base unsaturated heterocyclic ring contains <EMI ID = 187.1> en ce que X et X , qui peuvent être identiques ou différents, . désignent chacun un atome d'hydrogène, un radical alcoyle infé- in that X and X, which may be the same or different,. each denote a hydrogen atom, an inferior alkyl radical <EMI ID=188.1> <EMI ID = 188.1> <EMI ID=189.1> <EMI ID = 189.1> <EMI ID=190.1> <EMI ID=191.1> <EMI ID = 190.1> <EMI ID = 191.1> 2 à 4 et E désigne un atome d'oxygène ou de soufre. 2 to 4 and E denotes an oxygen or sulfur atom. <EMI ID=192.1> <EMI ID = 192.1> <EMI ID=193.1> <EMI ID = 193.1> désignent chacun un atome.d'hydrogène}, un radical alooyle infé.rieur ou, benzyle 'ou un atone d'halogène et 1 est un.nombre entier each denote a hydrogen atom, a lower alkyl group or, benzyl 'or a halogen atom and 1 is an integer. <EMI ID=194.1> <EMI ID = 194.1> <EMI ID=195.1> <EMI ID = 195.1> gène, un radical méthyle, un atome de brome, un radical amino ou gene, a methyl radical, a bromine atom, an amino radical or <EMI ID=196.1> <EMI ID = 196.1> <EMI ID=197.1> <EMI ID = 197.1> <EMI ID=198.1> <EMI ID = 198.1> en ce qu&#65533; le noyau hétérocyclique non saturé est un noyau imida- in that &#65533; the unsaturated heterocyclic ring is an imida- ring <EMI ID=199.1> <EMI ID = 199.1> <EMI ID=200.1> <EMI ID = 200.1> <EMI ID=201.1> <EMI ID = 201.1> <EMI ID=202.1> <EMI ID = 202.1> 21.-Compositions pharmaceutiques, contenant comme ingrédient. actif, ou comme l'un des ingrédients actifs, une quantité efficace d'un composé suivant l'une ou-l'autre des reTendi- 21.-Pharmaceutical compositions, containing as an ingredient. active, or as one of the active ingredients, an effective amount of a compound according to either of the claims <EMI ID=203.1> <EMI ID = 203.1> <EMI ID=204.1> <EMI ID = 204.1> <EMI ID=205.1> <EMI ID = 205.1> groupe <EMI ID=206.1> <EMI ID=207.1> group <EMI ID = 206.1> <EMI ID = 207.1> <EMI ID=208.1> <EMI ID = 208.1> <EMI ID=209.1> <EMI ID = 209.1> <EMI ID=210.1> <EMI ID = 210.1> <EMI ID=211.1> <EMI ID = 211.1> <EMI ID=212.1> <EMI ID = 212.1> <EMI ID=213.1> <EMI ID = 213.1>
BE779775A 1971-03-09 1972-02-24 DERIVATIVES OF UREA, METHOD FOR PREPARING THEM AND THEIR APPLICATIONS BE779775A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB635271A GB1338169A (en) 1971-03-09 1971-03-09 Ureas thioureas and guanidines
GB3433471 1971-07-22

Publications (1)

Publication Number Publication Date
BE779775A true BE779775A (en) 1972-08-24

Family

ID=26240626

Family Applications (1)

Application Number Title Priority Date Filing Date
BE779775A BE779775A (en) 1971-03-09 1972-02-24 DERIVATIVES OF UREA, METHOD FOR PREPARING THEM AND THEIR APPLICATIONS

Country Status (21)

Country Link
JP (5) JPS5324422B1 (en)
AR (2) AR197080A1 (en)
BE (1) BE779775A (en)
CY (1) CY856A (en)
DK (1) DK139870B (en)
EG (1) EG10876A (en)
ES (1) ES400587A1 (en)
FI (1) FI60393C (en)
HK (1) HK55176A (en)
HU (1) HU164509B (en)
IE (1) IE36050B1 (en)
IL (1) IL38821A (en)
IT (1) IT1041101B (en)
KE (1) KE2625A (en)
MY (1) MY7600228A (en)
NO (1) NO133196C (en)
PH (2) PH12207A (en)
SE (3) SE402288B (en)
SG (1) SG28576G (en)
SU (1) SU460628A3 (en)
ZM (1) ZM3672A1 (en)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2344833A1 (en) * 1972-09-05 1974-03-14 Smith Kline French Lab GUANIDINE, THEIR SALT, PROCESS FOR THEIR MANUFACTURING AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS
DE2344779A1 (en) * 1972-09-05 1974-03-14 Smith Kline French Lab CYANGUANIDINE, THEIR SALT, PROCESS FOR THEIR PRODUCTION AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS
US4000296A (en) * 1972-09-05 1976-12-28 Smith Kline & French Laboratories Limited Imidazole alkylguanidine compounds
US4083988A (en) * 1972-09-05 1978-04-11 Smith Kline & French Laboratories Limited Pharmacologically active compounds
US4129657A (en) 1975-03-21 1978-12-12 Smith, Kline & French Laboratories Limited Imidazole guanidines and use as inhibitors of histamine activity

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL56265A (en) * 1977-12-28 1982-08-31 Om Lab Sa Process for preparing imidazolyl methylthio guanidine derivatives and a novel intermediate therefor
JPH07107054B2 (en) * 1987-05-20 1995-11-15 株式会社日本触媒 Process for producing 4-methyl-5-[(2-aminoethyl) thiomethyl] imidazole dihydrochloride
JP2933739B2 (en) * 1990-04-09 1999-08-16 明治製菓株式会社 Thiazole or imidazole derivatives and anti-ulcer agents

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2344833A1 (en) * 1972-09-05 1974-03-14 Smith Kline French Lab GUANIDINE, THEIR SALT, PROCESS FOR THEIR MANUFACTURING AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS
DE2344779A1 (en) * 1972-09-05 1974-03-14 Smith Kline French Lab CYANGUANIDINE, THEIR SALT, PROCESS FOR THEIR PRODUCTION AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS
US4000296A (en) * 1972-09-05 1976-12-28 Smith Kline & French Laboratories Limited Imidazole alkylguanidine compounds
US4083988A (en) * 1972-09-05 1978-04-11 Smith Kline & French Laboratories Limited Pharmacologically active compounds
US4129657A (en) 1975-03-21 1978-12-12 Smith, Kline & French Laboratories Limited Imidazole guanidines and use as inhibitors of histamine activity

Also Published As

Publication number Publication date
JPS5811948B2 (en) 1983-03-05
DK139870C (en) 1979-10-08
SG28576G (en) 1987-04-03
SU460628A3 (en) 1975-02-15
SE7610842L (en) 1976-09-30
NO133196B (en) 1975-12-15
IL38821A0 (en) 1972-10-29
IE36050B1 (en) 1976-08-04
NO133196C (en) 1976-03-24
JPS53119867A (en) 1978-10-19
PH12207A (en) 1978-11-29
JPS5459275A (en) 1979-05-12
MY7600228A (en) 1976-12-31
FI60393B (en) 1981-09-30
ZM3672A1 (en) 1972-10-23
IT1041101B (en) 1980-01-10
JPS53119868A (en) 1978-10-19
IE36050L (en) 1972-09-09
SE410103B (en) 1979-09-24
IL38821A (en) 1975-05-22
CY856A (en) 1976-09-10
DK139870B (en) 1979-05-07
SE430689B (en) 1983-12-05
JPS5324422B1 (en) 1978-07-20
AR197093A1 (en) 1974-03-15
JPS5732063B2 (en) 1982-07-08
HK55176A (en) 1976-09-17
FI60393C (en) 1982-01-11
AR197080A1 (en) 1974-03-15
JPS5742068B2 (en) 1982-09-07
SE7412680L (en) 1974-10-09
PH12247A (en) 1978-12-12
SE402288B (en) 1978-06-26
ES400587A1 (en) 1975-07-16
HU164509B (en) 1974-02-28
KE2625A (en) 1976-05-28
JPS53119869A (en) 1978-10-19
EG10876A (en) 1976-07-31

Similar Documents

Publication Publication Date Title
EP0591057B1 (en) Arylalkyl(thio)amides with melatonine receptor selectivity and process for their preparation
EP0399856B1 (en) Pteridin-4 (3H)-ones, processes for their preparation and medicaments containing them
LU79761A1 (en) PROCESS FOR THE PREPARATION OF NEW PHTALAZINE COMPOUNDS AND A PHARMACEUTICAL COMPOSITION CONTAINING THEM
CH619463A5 (en)
EP0073161A1 (en) Pyridazine derivatives active on the central nerve system
EP0624575A1 (en) Substituted indoles and pharmaceutical compositions containing them
EP0117771B1 (en) Imino-2 pyrrolidines, process for their preparation and their therapeutical use
BE779775A (en) DERIVATIVES OF UREA, METHOD FOR PREPARING THEM AND THEIR APPLICATIONS
WO1993020046A1 (en) Indan-1,3-dione and indan-1,2,3-trione derivatives, processes for preparation of same and their use as therapeutic agents
EP0021940A1 (en) Amino derivatives of benzothiazole, process for their preparation and their use in therapy
FR2534582A1 (en) NOVEL BENZOFURAN AND BENZOTHIOPHENE DERIVATIVES, USEFUL AS ANTI-HYPERURICEMIA AND ANTI-HYPERTENSION AGENTS, AND PROCESS FOR THEIR MANUFACTURE
EP0459887A1 (en) Pyrazole-orthodialkyl-benzamide derivatives with an anticonvulsive activity, process for preparation and pharmaceutical composition
BE884387A (en) COMPOSITION BASED ON ARYLOXYALKYLAMINOBENZOIC ACIDS, SALTS AND ESTERS THEREOF
CH407088A (en) Process for the preparation of 4-halo-3-sulfamoyl-benzoic acid derivatives
EP0000452B1 (en) 1,2,4-oxadiazol derivatives, their preparation and application in pharmaceutical compositions
FR2551063A1 (en) New 2,5-dimethylpyrroles, process for preparing them and their therapeutic use
CH650254A5 (en) QUINOLONES, PROCESSES FOR THEIR PREPARATION AND THERAPEUTIC COMPOSITIONS CONTAINING THEM.
EP0002401B1 (en) Derivatives of naphthalene, process for their preparation and their therapeutic application
CA1211105A (en) Process for the preparation of p-acylaminophenol derivatives and derivatives thus obtained
EP0294258A1 (en) Hydrazine derivatives, process for obtaining them and pharmaceutical composition containing them
EP0196943A1 (en) 8-Thiotetrahydroquinoleine derivatives and their salts
WO2000063170A1 (en) Cyclobutene-3,4-dione derivatives as inhibitors of phosphodiesterase 5
CH392483A (en) Process for the preparation of new esters of 4-halo-3-sulfamoyl-benzoic acids
EP0275221B1 (en) N-(1h-indol-4-yl) benzamide derivatives, their salts and their use as medicines, and composition containing them
BE858864A (en) NEW ESTERS OF PHENYL- AND PYRIDINE-3-CARBOXYLIC ACIDS AND PROCESS FOR THEIR PREPARATION

Legal Events

Date Code Title Description
RE20 Patent expired

Owner name: SMITH KLINE & FRENCH LABORATORIES LTD

Effective date: 19920224