BE776316R - Phenylacetic acid derivs - as antiinflammatory agents - Google Patents

Phenylacetic acid derivs - as antiinflammatory agents

Info

Publication number
BE776316R
BE776316R BE776316A BE776316A BE776316R BE 776316 R BE776316 R BE 776316R BE 776316 A BE776316 A BE 776316A BE 776316 A BE776316 A BE 776316A BE 776316 R BE776316 R BE 776316R
Authority
BE
Belgium
Prior art keywords
emi
alkyl
acid
amino
chloride
Prior art date
Application number
BE776316A
Other languages
French (fr)
Inventor
J Diamond
N J Santora
G H Douglas
Original Assignee
Rorer Inc William H
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
Priority claimed from US00152366A external-priority patent/US3821268A/en
Priority claimed from US00152387A external-priority patent/US3852323A/en
Priority claimed from US00152451A external-priority patent/US3821267A/en
Priority claimed from BE773385A external-priority patent/BE773385A/en
Priority claimed from US195825A external-priority patent/US3867434A/en
Application filed by Rorer Inc William H filed Critical Rorer Inc William H
Application granted granted Critical
Publication of BE776316R publication Critical patent/BE776316R/en

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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/27—Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/26—Cyanate or isocyanate esters; Thiocyanate or isothiocyanate esters
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
    • C07C201/06—Preparation of nitro compounds
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    • C07C229/42—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino groups bound to carbon atoms of at least one six-membered aromatic ring and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton with carboxyl groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by saturated carbon chains
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    • C07C233/46—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
    • C07C233/47—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
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    • C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C323/56—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton containing six-membered aromatic rings
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    • C07C327/00—Thiocarboxylic acids
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    • C07C327/32—Esters of monothiocarboxylic acids having sulfur atoms of esterified thiocarboxyl groups bound to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
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    • 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
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  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
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  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Cpds. (I): (where Ris alkyl, cycloalkyl, cycloalkenyl, aryloxy, arylthio, arylamino, aroyl, heterocyclyl or aryl opt. substd. by Y; Y is H, halogen, alkyl, NO2, amino, acyl-, alkyl- or di-alkyl-amino, SH, acylthio, alkylthio, alkylsulphinyl, alkylsulphonyl, OH, alkoxy, acyloxy, haloalkyl, CN, or acetyl; n is 0-2; m is 0-2; n+m = 0-2; Ralpha, Rbeta, Gamma are H or alkyl; X is halogen, OH, alkoxy, acyloxy, aryloxy, carboalkoxy, carbamyloxy, alkyl- or di-alkylcarbamyloxy, alkane-, benzene- or toluene-sulphonyloxy, carboxyacyloxy, carboxyaroyloxy, SH, alkylthio, acylthio, aroylthio, sulpho, sulphino, alkylsulphinyl, alkylsulphonyl, thioacylthio, thiosulpho, thiocyanato, amidinothio, carbamylthio, alkyl- and di-alkylcarbamylthio, alkoxythiocarbonylthio, alkoxycarbonylthio, dialkylthiocarbamylthio, aralkoxycarbonylthio, carboxyaroylthio, or carboxyacylthio; Z is H, OH, alkoxy, aralkoxy, amino, alkyl-, dialkyl- or cycloalkyl-amino, (where A is alkylideneyl or heterocyclylalkylidene.yl), hydroxyamino, hydrazinyl or OM (where M is alkali metal, alkaline earth metal, Al or NH4), provided that when n=0 and m=0, X is not OH, Oalkyl, SO2 alkyl or halogen, but if Rbeta is H and R is cycloalkyl, X may be halogen or SO2 alkyl; also provided that when n=0, m=1, Ralpha=alkyl and R is cycloalkyl, X is not H; and also provided that when n=1 and m=1 or when n=0 and m=2 while Ralpha, Rbeta and Gamma are H, X is not OH if R is Ph) are prepd. from (I; X=OH and Z=OAlkyl) by halogenation and opt. conversion of Z=OAlkyl to other values of Z, or by halogenation of (I;X=OSO2Alkyl) with a metal halide and then conversion of (I; X=Hal or OH or OSO2Alkyl) to other values of X by reaction with nucleophilic reagents or by esterification (when X=OH).

Description

       

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matlon.

  
La Demanderesse a établi, en outre,' que ces acides alpha-, 

  
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tion ont des propriétés analgésiques et antipyrétiques utiles et

  
qu'ils se prêtent au traitement de la douleur et de la fièvre.

  
La Demanderesse a découvert aussi une classe entièrement

  
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de pour synthétiser ces composés.

  
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substituants.

  
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est le suivant : 

  

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Tale :

  

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n a une valeur de 0 à 2; 

  
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caux alcoyle inférieurs; 

  
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La position para est la position pour les sub-

  
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Des composés encore davantage préfères en raison de 

  
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dans esquels le .radical représenté par X occupe la position

  
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sium; 

  
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 <EMI ID=44.1>   <EMI ID=45.1> 

  
drogénation catalytique en présence d'oxyde de platina au moyen de borohydrure de sodium. Il est avantageux de partir d'un compo-

  
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La_ position alpha 

  
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de sodium et d'anhydride acétique, suivant la technique décrite par

  
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de la réaction. La réaction petit être exécutée aussi à l'aide 

  
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Une combinaison des réactions ci-dessus permet d'obtenir

  
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l'acide. 

  

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dium. 

  

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 <EMI ID=95.1>  

  

 <EMI ID=96.1> 
 

  
 <EMI ID=97.1> 

  
 <EMI ID=98.1> 

  
d'une aminé tertiaire telle que la pyridine, la picoline ou,' la

  
 <EMI ID=99.1> 

  
nesulfonyle.

  

 <EMI ID=100.1> 
 

  

 <EMI ID=101.1> 
 

  

 <EMI ID=102.1> 
 

  
 <EMI ID=103.1> 

  
dut 

  

 <EMI ID=104.1> 


  
 <EMI ID=105.1>  <EMI ID=106.1>  

  
 <EMI ID=107.1> 

  

 <EMI ID=108.1> 


  
 <EMI ID=109.1> 

  
 <EMI ID=110.1> 

  
halogéné correspondant

  

 <EMI ID=111.1> 


  
 <EMI ID=112.1> 

  
 <EMI ID=113.1> 

  

 <EMI ID=114.1> 


  
 <EMI ID=115.1>  
 <EMI ID=116.1> 
 les sels d'addition diacides peuvent être obtenus par <EMI ID=117.1> 

  

 <EMI ID=118.1> 


  
 <EMI ID=119.1>   <EMI ID=120.1> 

  

 <EMI ID=121.1> 


  
 <EMI ID=122.1> 
 <EMI ID=123.1> 
 
 <EMI ID=124.1> 
 <EMI ID=125.1> 
 <EMI ID=126.1> 
 
 <EMI ID=127.1> 
 <EMI ID=128.1> 

  

 <EMI ID=129.1> 
 

  

 <EMI ID=130.1> 
 

  

 <EMI ID=131.1> 


  
 <EMI ID=132.1> 

  
dant. 

  

 <EMI ID=133.1> 
 

  
 <EMI ID=134.1> 

  

 <EMI ID=135.1> 


  
 <EMI ID=136.1> 
 <EMI ID=137.1> 
 
 <EMI ID=138.1> 
  <EMI ID=139.1>  ,que substitué correspondant..

  

 <EMI ID=140.1> 


  
 <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> 


  
Le composé peut être de plus diazoté et le produit intermédiaire peut participer à une addition avec le cyanure de cuivre pour donner le cyanophénylhydroxyalcanoate.

  

 <EMI ID=166.1> 


  
L'aminophénylhydroxyalcanoate peut être diazoté et le produit obtenu peut être soumis à une réaction avec l'éthylxanthate de potassium avant une hydrolyse donnant l'acide mercapto-

  
 <EMI ID=167.1> 

  
noate. Ce dernier composé^ à son tours peut recevoir un radical alcoyle inférieur donnant le composé à radical alcoylthio inférieur et ce dernier radical peut être oxydé sur le composé en ra-

  
 <EMI ID=168.1> 

  
ou bien recevoir un radical àcyle donnant le composé à radical acylthio. 

  

 <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> 

  
en autres radicaux de la façon déjà indiquée.. 

  
Par exemple, lorsque R représente le radical phényle, la réaction suivante est possible. 

  

 <EMI ID=178.1> 
 

  

 <EMI ID=179.1> 
 

  

 <EMI ID=180.1> 


  
 <EMI ID=181.1>  

  
 <EMI ID=182.1> 

  
tuants requis. 

  
 <EMI ID=183.1> 

  
 <EMI ID=184.1> 

  
 <EMI ID=185.1> 

  
 <EMI ID=186.1> 

  
 <EMI ID=187.1> 

  
priétés et les solubilités sont différentes et qui peuvent donc être séparés par cristallisation fractionnée. Lorsque les sels ont été totalement séparés par cristallisations successives, la base est éliminée par hydrolyse et l'acide est ainsi isole sous la <EMI ID=188.1>  <EMI ID=189.1> 

  
 <EMI ID=190.1>   <EMI ID=191.1> 

  
 <EMI ID=192.1> 

  
 <EMI ID=193.1> 

  
 <EMI ID=194.1>   <EMI ID=195.1> 

  
 <EMI ID=196.1> 

  
nent pour l'usage topique, parentéral ou rectal.

  
Les diverses formes dosées peuvent être préparées suivant toute technique' classique en pharmacie et peuvent comprendre

  
 <EMI ID=197.1> 

  
matisants, colorants, agents de conservation etc. 'De plus, les acides alcano3:ques actifs et leurs dérivés peuvent être administrés seuls ou en association avec des antiacides, comme le bicarbonate de sodium, le carbonate de magnésium, l'hydroxyde de magnésium, l'hydroxyde d'aluminium, le silicate d'aluminium etc., et avec des excipients non toxiques pharmaceutiquement acceptables.

  
.Ces excipients peuvent être, par exemple, des diluants inertes, oomme le carbonate de calcium, le lactose etc., des agents de granulation et ameublissants, comme le' stéarate 'de magnésium, le talc etc.; des liants comme l'amidon, la gélatine etc.; des agents de mise en suspension, comme la méthylcellulose et les huiles végétales etc.; des dispersants, comme la lécithine etc.; des épaississants, comme la cire d'abeille, la paraffine dure etc., des émulsionnants, comme les gommes naturelles etc.,et des exci- <EMI ID=198.1> 

  
neglycols, entre autres. 

  
Divers essais peuvent être exécutés sur des animaux

  
pour montrer la capacité des acides alcanoiques de l'invention et de leurs dérivés à exercer des effets qui peuvent être mis en corrélation avec l'activité anti-inflammatoire chez l'homme. L'un de ces essais est celui de l'oedème de la patte induit par la carrageenine qui montre l'aptitude des composés de l'invention à inhiber l'oedème induit par l'injection d'un agent inflammatoire, comme la carrageenine,dans le tissu de la patte du rat, la comparaison étant établie avec des animaux témoins ne manifestant pas

  
 <EMI ID=199.1> 

  
une corrélation avec l'activité anti-inflammatoire chez l'homme

  
et est classique pour l'appréciation de l'effet anti-inflammatoire. La corrélation peut être démontrée par l'efficacité de certains composés connus comme cliniquement actifs, ainsi qu'il en est de l'acide acétylsalicylique, de la phénylbutazone, de la cortisone, de l'hydrocortisone et de la prednisolone. En raison des résul-

  
 <EMI ID=200.1> 

  
être considérés comme étant des agents anti-inflammatoires. 

  
 <EMI ID=201.1> 

  
cobaye.

  
La préparation des composés de l'invention est :illustrée

  
 <EMI ID=202.1> 

  
tîoa.  EXEMPLE 1,.- 

  
 <EMI ID=203.1> 

  
On agite le mélange pendant encore 1 heure, puis on le laisse re-

  
 <EMI ID=204.1> 

  
 <EMI ID=205.1> 

  
 <EMI ID=206.1> 

  
 <EMI ID=207.1> 

  
 <EMI ID=208.1> 

  
se les solvants du filtrat par distillation sous pression rédui- <EMI ID=209.1> 

  
 <EMI ID=210.1> 

  
 <EMI ID=211.1> 

  
d'éthyle

  
 <EMI ID=212.1> 

  
 <EMI ID=213.1> 

  
 <EMI ID=214.1> 

  
 <EMI ID=215.1>   <EMI ID=216.1>   <EMI ID=217.1> 

  
 <EMI ID=218.1> 

  
sus par les composés du tableau III et l'ester méthylique du chlorure d'oxalyle par les composés du tableau II, on obtient les composés correspondants.

  
 <EMI ID=219.1> 

  
 <EMI ID=220.1> 

  
b'enzaldéhyde (0,1 mole) au bain de vapeur avec 13,2 g d'acide maIonique et 95 ml de pyridine contenant 5 gouttes de pipéridine.

  
 <EMI ID=221.1>   <EMI ID=222.1> 

  
 <EMI ID=223.1> 

  
d'eau glacée.. On recueille par filtration le solide qui se sépare, qu'on lave à l'eau froide et qu'on remet en suspension dans
200 ml d'eau froide, qu'on recueille à nouveau par filtration,

  
 <EMI ID=224.1> 

  
 <EMI ID=225.1> 

  
nyl)cinnamique.

  
 <EMI ID=226.1> 

  
par l'acide méthylmalonique ou éthylmalonique., on obtient comme produits 

  
 <EMI ID=227.1> 

  
 <EMI ID=228.1> 

  
obtient les composés correspondants du tableau II.

  
 <EMI ID=229.1>   <EMI ID=230.1> 

  
 <EMI ID=231.1> 

  
 <EMI ID=232.1>   <EMI ID=233.1>  <EMI ID=234.1> 

  
 <EMI ID=235.1> 

  
 <EMI ID=236.1>  

  
 <EMI ID=237.1> 

  
 <EMI ID=238.1> 

  
 <EMI ID=239.1> 

  
 <EMI ID=240.1> 

  
 <EMI ID=241.1>  

  
 <EMI ID=242.1> 

  
 <EMI ID=243.1> 

  
 <EMI ID=244.1>  propionyle dans la réaction ci-dessus par. les chlorures de propio- 

  
 <EMI ID=245.1> 

  
 <EMI ID=246.1> 

  
 <EMI ID=247.1> 

  
 <EMI ID=248.1> 

  
 <EMI ID=249.1> 

  
 <EMI ID=250.1> 

  
 <EMI ID=251.1> 

  
de l'exemple 2, on obtient les composés correspondants.

  
 <EMI ID=252.1>  

  
 <EMI ID=253.1> 

  
 <EMI ID=254.1> 

  
 <EMI ID=255.1> 

  
 <EMI ID=256.1> 

  
 <EMI ID=257.1> 

  
réaction au reflux en l'agitant vivement pendant -1 heure.. On re-

  
 <EMI ID=258.1> 

  
 <EMI ID=259.1> 

  
 <EMI ID=260.1> 

  
la réaction ci-dessus par les cétones du tableau Ici-après, onobtient les composés correspondants cites au tableau II ci-après. 

  
 <EMI ID=261.1> 

  
 <EMI ID=262.1> 

  
 <EMI ID=263.1>  

  
 <EMI ID=264.1> 

  
 <EMI ID=265.1> 

  
 <EMI ID=266.1> 

  
 <EMI ID=267.1> 

  
 <EMI ID=268.1> 
-on chauffe le mélange au reflux sous agitation jusque ce .qu'il .

  
 <EMI ID=269.1> 

  
 <EMI ID=270.1> 

  
 <EMI ID=271.1>   <EMI ID=272.1> 

  
 <EMI ID=273.1> 

  
 <EMI ID=274.1> 

  
 <EMI ID=275.1>   <EMI ID=276.1> 

  
 <EMI ID=277.1> 

  
 <EMI ID=278.1> 

  
0. En répétant les opérations ci-dessus au moyen des réac-

  
 <EMI ID=279.1> 

  
tie A, on obtient les composés correspondants.

  
 <EMI ID=280.1> 

  
 <EMI ID=281.1>  <EMI ID=282.1> 

  
 <EMI ID=283.1> 

  
 <EMI ID=284.1> 

  
on exécute une extraction à l'éther. On lave les extraits éthérés

  
 <EMI ID=285.1> 

  
sodium'et ensuite avec de la saumure, après quoi on les sèche sur  <EMI ID=286.1> 

  
pondants.

  
 <EMI ID=287.1> 

  
 <EMI ID=288.1> 

  
 <EMI ID=289.1> 

  
 <EMI ID=290.1> 

  
 <EMI ID=291.1> 

  
l'eau, on le soumet à une extraction et on lave les extraits %. la

  
 <EMI ID=292.1> 

  
EXEMPLE 15.- 

  
 <EMI ID=293.1>   <EMI ID=294.1>  <EMI ID=295.1> 

  
 <EMI ID=296.1>   <EMI ID=297.1> 

  
butyrique 

  
 <EMI ID=298.1>   <EMI ID=299.1> 

  
butyrique '  <EMI ID=300.1> 

  
'butyrique 

  
 <EMI ID=301.1> 

  
butyrique   <EMI ID=302.1> 

  
 <EMI ID=303.1>   <EMI ID=304.1> 

  
136. acide 

  
butyrique 

  
 <EMI ID=305.1>  

  
 <EMI ID=306.1> 

  
butyrique 

  
 <EMI ID=307.1>   <EMI ID=308.1> 

  
butyrique

  
 <EMI ID=309.1> 

  
butyrique

  
 <EMI ID=310.1> 

  
 <EMI ID=311.1>  et" on le laisse cristalliser. On sépare par filtration le produit qu'on lave à l'eau et qu'on recristallise dans le benzène

  
 <EMI ID=312.1>  les composés corre spondants. 

  
 <EMI ID=313.1> 

  
 <EMI ID=314.1> 

  
 <EMI ID=315.1> 

  
Mante et on y ajoute alors, goutte à goutte sens agitation,

  
 <EMI ID=316.1>  

  
 <EMI ID=317.1> 

  
 <EMI ID=318.1> 

  
 <EMI ID=319.1> 

  
 <EMI ID=320.1> 

  
 <EMI ID=321.1> 

  
biphénylyl)lactate d'éthyle... 

  
 <EMI ID=322.1> 

  
 <EMI ID=323.1> 

  
 <EMI ID=324.1> 

  
bleau suivant. 

  
 <EMI ID=325.1> 

  
 <EMI ID=326.1> 

  
d'éthyle   <EMI ID=327.1> 

  
d'éthyle ..

  
26. a-méthyl-p-i-propylphénylglycolate d'éthyle

  
27. a-méthyl-p-t-butylphénylglycolate d'éthyle

  
 <EMI ID=328.1>   <EMI ID=329.1>   <EMI ID=330.1> 

  
d'éthyle'  /butyrate

  
 <EMI ID=331.1> 

  
 <EMI ID=332.1>   <EMI ID=333.1> 

  
ne pendant 3 heures 30 minutes. On sépare le catalyseur par

  
 <EMI ID=334.1> 

  
 <EMI ID=335.1> 

  
correspondants dont une liste représentative est donnée au ta-

  
 <EMI ID=336.1> 

T A B. L EAU 

  
 <EMI ID=337.1>   <EMI ID=338.1>   <EMI ID=339.1>  <EMI ID=340.1> 

  
 <EMI ID=341.1>  

  
 <EMI ID=342.1> 

  
(0,066 scie) en 5 minutes à de l'acide sulfurique concentré -,glacé et agité (18 ni) tandis qu'on refroidit le système. On ajoute

  
 <EMI ID=343.1> 

  
 <EMI ID=344.1> 

  
de l'addition de l'acide nitrique, on agite le mélange pendant .30 minutes, puis on le verse dans de l'eau. On alcalinise le mélange au moyen d'hydroxyde de sodium, puis on l'extrait à l'éther.

  
 <EMI ID=345.1> 

  
 <EMI ID=346.1> 

  
 <EMI ID=347.1> 

  
 <EMI ID=348.1> 

  
près à la neutralité après l'addition. On ajuste ensuite le pH

  
 <EMI ID=349.1> 

  
 <EMI ID=350.1> 

  
 <EMI ID=351.1>   <EMI ID=352.1> 

  
de 1'invention.

  
 <EMI ID=353.1> 

  
 <EMI ID=354.1> 

  
carbone dans de l'hydrogène sous une pression de 2 atmosphères à 

  
 <EMI ID=355.1> 

  
de pyridine. On agite le mélange de :réaction jusqu'au lendemain

  
 <EMI ID=356.1> 

  
 <EMI ID=357.1> 

  
pare le catalyseur par filtration et on -évapore le filtrat sous - <EMI ID=358.1>  <EMI ID=359.1> 

  
pendant 30 minutes. On agite le mélange de réaction pendant en-

  
 <EMI ID=360.1> 

  
On refroidit ensuite le mélange et on sépare le toluène" après ,.quoi on exécute une dessiccation sur du.sulfate de sodium et -une .

  
 <EMI ID=361.1> 

  
 <EMI ID=362.1> 

  
position spontanée. Après la décomposition, on soumet le nouveau

  
 <EMI ID=363.1>   <EMI ID=364.1> 

  
 <EMI ID=365.1>  

  
 <EMI ID=366.1> 

  
 <EMI ID=367.1> 

  
 <EMI ID=368.1> 

  
vention- . 

  
 <EMI ID=369.1> 

  
Acide

  
 <EMI ID=370.1> 

  
 <EMI ID=371.1> 

  
 <EMI ID=372.1> 

  
 <EMI ID=373.1> 

  
 <EMI ID=374.1> 

  
 <EMI ID=375.1> 

  
bronze de cuivre sous agitation et on chauffe le mélange lente-

  
 <EMI ID=376.1> 

  
sulfate, puis avec de l'eau, après quoi on le sèche sur du sulfate de sodium et on l'évaporé- sous vide. On cristallise le résidu

  
 <EMI ID=377.1> 

  
-On forme l'ester éthylique de cet acide par réaction de , <EMI ID=378.1> 

  
d'acide chlorhydrique anhydre. 

  
 <EMI ID=379.1>  

  
tîon.

  
 <EMI ID=380.1> 

  
 <EMI ID=381.1> 

  
l'extrait éthéré avec de l'eau, avec vue. solution diluée d'hydroxyde de sodium et avec'de l'eau, puis on le sèche sur du sulfate

  
 <EMI ID=382.1> 

  
 <EMI ID=383.1> 

  
d'hydrosyde de potassium. On chauffe le mélange de réaction au

  
 <EMI ID=384.1> 

  
capto-4-biphénylyl)lactique.

  
 <EMI ID=385.1> 

  
 <EMI ID=386.1> 

  
to de l'invention.

  
 <EMI ID=387.1> 

  
 <EMI ID=388.1>   <EMI ID=389.1> 

  
 <EMI ID=390.1> 

  
 <EMI ID=391.1> 

  
 <EMI ID=392.1>   <EMI ID=393.1> 

  
 <EMI ID=394.1> 

  
 <EMI ID=395.1> 

  
de l'invention, on peut obtenir les isomères correspondants.

  
 <EMI ID=396.1> 

  
 <EMI ID=397.1>  <EMI ID=398.1>   <EMI ID=399.1> 

  
phénylyl)lactate de sodium.

  
 <EMI ID=400.1> 

  
 <EMI ID=401.1> 

  
obtient les sels correspondants.

  
hydroxyde de sodium hydroxyde de potassium bydroxyde de calcium carbonate de potassium 'bicarbonate de magnésium 

  
B. A l'aide des divers acides de l'invention, on peut préparer les sels correspondants.

  
 <EMI ID=402.1> 

  
 <EMI ID=403.1> 

  
 <EMI ID=404.1> 

  
 <EMI ID=405.1> 

  
cette réaction les sels correspondants.

  
 <EMI ID=406.1>   <EMI ID=407.1> 

  
 <EMI ID=408.1> 

  
 <EMI ID=409.1> 

  
 <EMI ID=410.1> 

  
froide saturée de bicarbonate de sodium, puis deux ,:fois avec de l'eau glacée à raison de 250 ml à chaque reprise. On sèche la. solution éthérée sur du sulfate de sodium anhydre et on la filtre.

  
 <EMI ID=411.1> 

  
Le tableau ci-dessous donne une liste représentative des produits

  
 <EMI ID=412.1> 

TABLEAU 

  
 <EMI ID=413.1>   <EMI ID=414.1> 

  
 <EMI ID=415.1> 

  
d'éthyle   <EMI ID=416.1> 

  
63. a-chloro-p-(2-thiényl)phénylacétate d'éthyle  <EMI ID=417.1>   <EMI ID=418.1> 

  
d'éthyle - 

  
 <EMI ID=419.1>   <EMI ID=420.1> 

  
150. Y-chloro-Y-(3-trifluorométhyl-4-cyclohexylphényl)-

  
butyrate d'éthyle

  
 <EMI ID=421.1>   <EMI ID=422.1> 

  
 <EMI ID=423.1> 

  
dans la réaction ci-dessus, on obtient les amides correspondants.

  
 <EMI ID=424.1> 

  
Ces (100 ml au total), puis on la sèche sur.du sulfate de sodium.

  
 <EMI ID=425.1>   <EMI ID=426.1> 

  
 <EMI ID=427.1> 

  
 <EMI ID=428.1> 

  
 <EMI ID=429.1> 

  
on peut., par la. réaction ci-dessus, préparer les sels correspondants. 

  
 <EMI ID=430.1>  

  
 <EMI ID=431.1> 

  
la façon ci-dessus, préparer les composés correspondants.

  
 <EMI ID=432.1> 

  
 <EMI ID=433.1> 

  
 <EMI ID=434.1> 

  
avec 70 ml de éther de pétrole et on verse le tout dans 125 ml d'eau glacée. On sépare la phase organique qu'on lave avec une

  
 <EMI ID=435.1> 

  
che sur du sulfate de sodium anhydre et qu'on filtre, après quoi

  
 <EMI ID=436.1> 

  
 <EMI ID=437.1>  amides correspondants.

  
 <EMI ID=438.1> 

  
correspondants.

  
 <EMI ID=439.1> 

  
 <EMI ID=440.1>   <EMI ID=441.1> 

  
On- extrait le mélange aqueux et glycolique au moyen d'éther, puis on sèche l'extrait éthéré, on l'évapore à siccité et on distille

  
 <EMI ID=442.1> 

  
pionate d'éthyle. 

  
A. En répétant les opérations ci-dessus au moyen des divers bromoalcanoates et bromoalcanoamides de l'invention, on obtient les fluoroalcanoates et fluoroalcanoamides correspondants.

  
 <EMI ID=443.1> 

  
En hydrolysant les fluoroalcanoates de l'exemple 51 com-

  
 <EMI ID=444.1> 

  
correspondants.

  
 <EMI ID=445.1> 

  
 <EMI ID=446.1> 

  
 <EMI ID=447.1> 

  
acides fluoroalcanoiques.

  
 <EMI ID=448.1> 

  
 <EMI ID=449.1> 

  
 <EMI ID=450.1> 

  
anhydre. On évapore le mélange de réaction à siccité et on ex-

  
 <EMI ID=451.1> 

  
 <EMI ID=452.1> 

  
A. En exécutant les opérations ci-dessus au moyen des bromoalcanoates et bromoalcanoamides de l'invention, on obtient les iodoalcanoates et iodoalcanoamides correspondants.

  
EXEMPLE 55.- 

  
 <EMI ID=453.1> 

  
 <EMI ID=454.1> 

  
pondants.

  
EXEMPLE 56.-- 

  
En faisant réagir les acides iodoalcahoïques comme dans

  
 <EMI ID=455.1> 

  
noiques.

  
EXEMPLE 57. - 

  
 <EMI ID=456.1>  que (0,05 mole) et de 5 g d'hydrosulfure de sodium dans 100 ni

  
 <EMI ID=457.1> 

  
 <EMI ID=458.1> 

  
extrait-le résidu à l'éther, puis on lave l'extrait avec de l'eau et avec une solution saturée de chlorure de sodium, après quoi on le sèche et on l'évapore à siccité pour obtenir l'acide a-mercap-

  
 <EMI ID=459.1> 

  
A. En exécutant la réaction ci-dessus avec les acides chlo-

  
 <EMI ID=460.1> 

  
 <EMI ID=461.1> 

  
 <EMI ID=462.1> 

  
 <EMI ID=463.1> 

  
dans 60 ml de tétrahydrofuranne sec. On chauffe le mélange au reflux pendant 3 heures, puis on l'agite à la température ambian-

  
 <EMI ID=464.1> 

  
 <EMI ID=465.1> 

  
extrait le résidu dans de l'éther, puis on lave l'extrait éthéré avec de l'eau et avec une solution saturée de chlorure de sodium, après quoi on le sèche et on l'évapore jusqu'à siccité pour obte-

  
 <EMI ID=466.1> 

  
A. En exécutant la réaction ci-dessus au moyen des acides chloroalcanoïques, des chloroalcanoates et des chloroalcanoamides

  
 <EMI ID=467.1> 

  
méthylthioalcanoates et les méthylthioalcanoamides correspondants.

  
 <EMI ID=468.1> 

  
 <EMI ID=469.1> 

  
 <EMI ID=470.1> 

  
à une solution de 600 ml d'éthanol anhydre et de 21 g d'hydroxyde de potassium (0,317 mole). On ajoute au mélange 79 g d'acide

  
 <EMI ID=471.1> 

  
suit l'agitation pendant 15 heures. On recueille par filtration le solide qui se forme et on le lave à l'éthanol. On évapore le filtrat à siccité et on dissout, le résidu dans 500 ml d'éther, puis on lave la solution éthérée à plusieurs reprises avec de l'eau. Par séchage de la solution éthérée et évaporation de celle- <EMI ID=472.1>  <EMI ID=473.1>  <EMI ID=474.1> 

  
heures, puis on en chasse le solvant, on dissout le résidu dans de l'éther, on filtre le nélange et on lave la solution éthérée à l'eau froide. On sèche la solution éthérée sur du sulfate de magnésium et on 1,'évapore ensuite à siccité pour obtenir 1-1-acide

  
 <EMI ID=475.1> 

  
dants. 

  
EXEMPLE 61.-

  
 <EMI ID=476.1> 

  
 <EMI ID=477.1> 

  
 <EMI ID=478.1> 

  
 <EMI ID=479.1> 

  
 <EMI ID=480.1> 

  
 <EMI ID=481.1>   <EMI ID=482.1> 

  
 <EMI ID=483.1> 

  
 <EMI ID=484.1> 

  
 <EMI ID=485.1> 

  
 <EMI ID=486.1> 

  
rée et on 1* évapore à siccité pour obtenir l'acide a-thiocyanato-

  
 <EMI ID=487.1> 

  
nate de sodium (0,1 mole) à une solution de 0,12 sole de sulfite :

  
 <EMI ID=488.1> 

  
réaction pendant 15 heures, puis on le filtre et on lave le ré-

  
 <EMI ID=489.1>  

  
 <EMI ID=490.1> 

  
nate d'éthyle

  
On chauffe au reflux pendant 2 heures un mélange de

  
 <EMI ID=491.1> 

  
(0,023 mole) et de 5,7 g de thiosulfate de sodium pentahydraté

  
 <EMI ID=492.1> 

  
 <EMI ID=493.1> 

  
poursuit le chauffage au reflux pendant 30 minutes. On évapore ensuite le mélange de réaction à siccité sous vide, on exécute

  
une distillation azéotropique avec de l'éthanol et on évapore

  
à nouveau la phase liquide à siccité sous vide. On triture le résidu dans de l'éther, on filtre le mélange et on évapore la solution à siccité. On triture le résidu à nouveau avec de l'hexane et on dissout la gomme résultante dans de l'alcool, puis on évapore la solution à siccité sous vide pour obtenir le sel de sodium

  
 <EMI ID=494.1> 

  
A. En exécutant la réaction ci-dessus au moyen des chloro'alcanoates et chloroalcanoamides de l'invention, on obtient les thiosulfoalcanoates et thiosulfoalcaiioamides correspondants. EXEMPLE 6?.- 

  
 <EMI ID=495.1> 

  
leurs esters et amides de l'invention dans les réactions ci-dessus; on obtient les acides amidinoalcanoiques de même que les esters et amides correspondants. 

  
 <EMI ID=496.1> 

  
nique. 

  
On dissout 36,3 g d'éthylxanthate de potassium (0,22 mole) dans 150 ml d'éthanol absolu par agitation. On ajoute à la

  
 <EMI ID=497.1> 

  
 <EMI ID=498.1>   <EMI ID=499.1> 

  
 <EMI ID=500.1> 

  
 <EMI ID=501.1> 

  
 <EMI ID=502.1> 

  
 <EMI ID=503.1>  

  
 <EMI ID=504.1> 

  
procédé ci-dessus par le chlorure de carbaayle (préparé in situ

  
 <EMI ID=505.1> 

  
 <EMI ID=506.1>  .ters et amides correspondants.

  
EXEMPLE 69.- 

  
 <EMI ID=507.1> 

  
nique.



   <EMI ID = 1.1>

  
 <EMI ID = 2.1>

  
 <EMI ID = 3.1>

  
 <EMI ID = 4.1>

  
 <EMI ID = 5.1>

  
matlon.

  
The Applicant has further established that these alpha- acids,

  
 <EMI ID = 6.1>

  
 <EMI ID = 7.1>

  
tion have useful analgesic and antipyretic properties and

  
that they lend themselves to the treatment of pain and fever.

  
The Applicant has also discovered a class entirely

  
 <EMI ID = 8.1> <EMI ID = 9.1>

  
to synthesize these compounds.

  
 <EMI ID = 10.1>

  
 <EMI ID = 11.1>

  
 <EMI ID = 12.1>

  
 <EMI ID = 13.1>

  
substituents.

  
 <EMI ID = 14.1>

  
is the next :

  

 <EMI ID = 15.1>


  
 <EMI ID = 16.1>

  
Tale:

  

 <EMI ID = 17.1>


  
 <EMI ID = 18.1>

  
 <EMI ID = 19.1>

  
 <EMI ID = 20.1>

  
n has a value of 0 to 2;

  
 <EMI ID = 21.1>

  
 <EMI ID = 22.1>

  
lower alkyl calluses;

  
 <EMI ID = 23.1>

  
 <EMI ID = 24.1>

  
The para position is the position for the sub-

  
 <EMI ID = 25.1> <EMI ID = 26.1>

  
 <EMI ID = 27.1>
 <EMI ID = 28.1>
  <EMI ID = 29.1>
 <EMI ID = 30.1>
 <EMI ID = 31.1>

  

 <EMI ID = 32.1>


  
 <EMI ID = 33.1>

  

 <EMI ID = 34.1>


  
Even more preferred compounds due to

  
 <EMI ID = 35.1>

  
 <EMI ID = 36.1>

  
in which the .radical represented by X occupies the position

  
 <EMI ID = 37.1>

  
 <EMI ID = 38.1>

  
 <EMI ID = 39.1>

  
 <EMI ID = 40.1>

  
 <EMI ID = 41.1>

  
 <EMI ID = 42.1>

  
sium;

  
 <EMI ID = 43.1>

  
 <EMI ID = 44.1> <EMI ID = 45.1>

  
Catalytic drogenation in the presence of platinum oxide by means of sodium borohydride. It is advantageous to start from a compo-

  
 <EMI ID = 46.1>

  

 <EMI ID = 47.1>


  
 <EMI ID = 48.1>

  
The_ alpha position

  
 <EMI ID = 49.1>

  
 <EMI ID = 50.1>

  
 <EMI ID = 51.1>

  

 <EMI ID = 52.1>


  
 <EMI ID = 53.1>

  

 <EMI ID = 54.1>


  
 <EMI ID = 55.1>

  
 <EMI ID = 56.1>

  
 <EMI ID = 57.1>

  
sodium and acetic anhydride, according to the technique described by

  
 <EMI ID = 58.1>

  
 <EMI ID = 59.1>

  
 <EMI ID = 60.1>

  

 <EMI ID = 61.1>
 

  
 <EMI ID = 62.1>

  
 <EMI ID = 63.1>

  
 <EMI ID = 64.1>

  
of the reaction. The reaction can also be carried out using

  
 <EMI ID = 65.1>
 <EMI ID = 66.1>
  <EMI ID = 67.1>

  

 <EMI ID = 68.1>


  
 <EMI ID = 69.1>

  

 <EMI ID = 70.1>


  
 <EMI ID = 71.1> <EMI ID = 72.1>
 <EMI ID = 73.1>
 
 <EMI ID = 74.1>
 <EMI ID = 75.1>
 <EMI ID = 76.1>
 <EMI ID = 77.1>

  

 <EMI ID = 78.1>


  
 <EMI ID = 79.1>

  

 <EMI ID = 80.1>


  
A combination of the above reactions makes it possible to obtain

  
 <EMI ID = 81.1> <EMI ID = 82.1>

  

 <EMI ID = 83.1>


  
 <EMI ID = 84.1>

  

 <EMI ID = 85.1>


  
 <EMI ID = 86.1>

  
acid.

  

 <EMI ID = 87.1>
 

  

 <EMI ID = 88.1>


  
 <EMI ID = 89.1>

  

 <EMI ID = 90.1>


  
 <EMI ID = 91.1>

  

 <EMI ID = 92.1>
 

  
 <EMI ID = 93.1>

  
dium.

  

 <EMI ID = 94.1>


  
 <EMI ID = 95.1>

  

 <EMI ID = 96.1>
 

  
 <EMI ID = 97.1>

  
 <EMI ID = 98.1>

  
of a tertiary amine such as pyridine, picoline or, 'the

  
 <EMI ID = 99.1>

  
nesulfonyl.

  

 <EMI ID = 100.1>
 

  

 <EMI ID = 101.1>
 

  

 <EMI ID = 102.1>
 

  
 <EMI ID = 103.1>

  
had to

  

 <EMI ID = 104.1>


  
 <EMI ID = 105.1> <EMI ID = 106.1>

  
 <EMI ID = 107.1>

  

 <EMI ID = 108.1>


  
 <EMI ID = 109.1>

  
 <EMI ID = 110.1>

  
corresponding halogen

  

 <EMI ID = 111.1>


  
 <EMI ID = 112.1>

  
 <EMI ID = 113.1>

  

 <EMI ID = 114.1>


  
 <EMI ID = 115.1>
 <EMI ID = 116.1>
 diacid addition salts can be obtained by <EMI ID = 117.1>

  

 <EMI ID = 118.1>


  
 <EMI ID = 119.1> <EMI ID = 120.1>

  

 <EMI ID = 121.1>


  
 <EMI ID = 122.1>
 <EMI ID = 123.1>
 
 <EMI ID = 124.1>
 <EMI ID = 125.1>
 <EMI ID = 126.1>
 
 <EMI ID = 127.1>
 <EMI ID = 128.1>

  

 <EMI ID = 129.1>
 

  

 <EMI ID = 130.1>
 

  

 <EMI ID = 131.1>


  
 <EMI ID = 132.1>

  
before.

  

 <EMI ID = 133.1>
 

  
 <EMI ID = 134.1>

  

 <EMI ID = 135.1>


  
 <EMI ID = 136.1>
 <EMI ID = 137.1>
 
 <EMI ID = 138.1>
  <EMI ID = 139.1>, that substituted corresponding ..

  

 <EMI ID = 140.1>


  
 <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>


  
The compound can further be diazotized and the intermediate can participate in addition with copper cyanide to give cyanophenylhydroxyalkanoate.

  

 <EMI ID = 166.1>


  
The aminophenylhydroxyalkanoate can be diazotized and the product obtained can be subjected to a reaction with potassium ethylxanthate before hydrolysis to give mercapto- acid.

  
 <EMI ID = 167.1>

  
noate. The latter compound in its turn can receive a lower alkyl radical giving the compound containing a lower alkylthio radical and the latter radical can be oxidized on the compound in ra-

  
 <EMI ID = 168.1>

  
or alternatively receive a alkyl radical giving the compound containing an acylthio radical.

  

 <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 other radicals as already indicated.

  
For example, when R represents the phenyl radical, the following reaction is possible.

  

 <EMI ID = 178.1>
 

  

 <EMI ID = 179.1>
 

  

 <EMI ID = 180.1>


  
 <EMI ID = 181.1>

  
 <EMI ID = 182.1>

  
killing required.

  
 <EMI ID = 183.1>

  
 <EMI ID = 184.1>

  
 <EMI ID = 185.1>

  
 <EMI ID = 186.1>

  
 <EMI ID = 187.1>

  
priities and solubilities are different and can therefore be separated by fractional crystallization. When the salts have been completely separated by successive crystallizations, the base is removed by hydrolysis and the acid is thus isolated under the <EMI ID = 188.1> <EMI ID = 189.1>

  
 <EMI ID = 190.1> <EMI ID = 191.1>

  
 <EMI ID = 192.1>

  
 <EMI ID = 193.1>

  
 <EMI ID = 194.1> <EMI ID = 195.1>

  
 <EMI ID = 196.1>

  
nent for topical, parenteral or rectal use.

  
The various dosage forms can be prepared according to any technique conventional in pharmacy and can include

  
 <EMI ID = 197.1>

  
mattifying agents, coloring agents, preservatives etc. 'In addition, active alkano acids and their derivatives can be administered alone or in combination with antacids, such as sodium bicarbonate, magnesium carbonate, magnesium hydroxide, aluminum hydroxide, silicate aluminum etc., and with non-toxic pharmaceutically acceptable excipients.

  
These excipients can be, for example, inert diluents, such as calcium carbonate, lactose etc., granulating and softening agents, such as magnesium 'stearate', talc etc .; binders such as starch, gelatin etc .; suspending agents, such as methylcellulose and vegetable oils etc .; dispersants, such as lecithin etc .; thickeners, such as beeswax, hard paraffin etc., emulsifiers, such as natural gums etc., and exci- <EMI ID = 198.1>

  
neglycols, among others.

  
Various tests can be performed on animals

  
to show the ability of the alkanoic acids of the invention and their derivatives to exert effects which can be correlated with anti-inflammatory activity in humans. One of these tests is that of edema of the paw induced by carrageenin, which shows the ability of the compounds of the invention to inhibit the edema induced by the injection of an inflammatory agent, such as carrageenin, in rat paw tissue, the comparison being made with control animals not showing

  
 <EMI ID = 199.1>

  
correlation with anti-inflammatory activity in humans

  
and is conventional for the assessment of the anti-inflammatory effect. The correlation can be demonstrated by the efficacy of certain compounds known to be clinically active, as well as acetylsalicylic acid, phenylbutazone, cortisone, hydrocortisone and prednisolone. Due to the results

  
 <EMI ID = 200.1>

  
be regarded as anti-inflammatory agents.

  
 <EMI ID = 201.1>

  
guinea pig.

  
The preparation of the compounds of the invention is: illustrated

  
 <EMI ID = 202.1>

  
tîoa. EXAMPLE 1, .-

  
 <EMI ID = 203.1>

  
The mixture is stirred for a further 1 hour, then allowed to re-stir.

  
 <EMI ID = 204.1>

  
 <EMI ID = 205.1>

  
 <EMI ID = 206.1>

  
 <EMI ID = 207.1>

  
 <EMI ID = 208.1>

  
se the solvents of the filtrate by distillation under reduced pressure- <EMI ID = 209.1>

  
 <EMI ID = 210.1>

  
 <EMI ID = 211.1>

  
ethyl

  
 <EMI ID = 212.1>

  
 <EMI ID = 213.1>

  
 <EMI ID = 214.1>

  
 <EMI ID = 215.1> <EMI ID = 216.1> <EMI ID = 217.1>

  
 <EMI ID = 218.1>

  
In addition to the compounds of Table III and the methyl ester of oxalyl chloride with the compounds of Table II, the corresponding compounds are obtained.

  
 <EMI ID = 219.1>

  
 <EMI ID = 220.1>

  
Benzaldehyde (0.1 mol) in a steam bath with 13.2 g of maIonic acid and 95 ml of pyridine containing 5 drops of piperidine.

  
 <EMI ID = 221.1> <EMI ID = 222.1>

  
 <EMI ID = 223.1>

  
of ice water. The solid which separates is collected by filtration, washed with cold water and resuspended in
200 ml of cold water, which is collected again by filtration,

  
 <EMI ID = 224.1>

  
 <EMI ID = 225.1>

  
nyl) cinnamic.

  
 <EMI ID = 226.1>

  
by methylmalonic or ethylmalonic acid., one obtains as products

  
 <EMI ID = 227.1>

  
 <EMI ID = 228.1>

  
obtains the corresponding compounds of Table II.

  
 <EMI ID = 229.1> <EMI ID = 230.1>

  
 <EMI ID = 231.1>

  
 <EMI ID = 232.1> <EMI ID = 233.1> <EMI ID = 234.1>

  
 <EMI ID = 235.1>

  
 <EMI ID = 236.1>

  
 <EMI ID = 237.1>

  
 <EMI ID = 238.1>

  
 <EMI ID = 239.1>

  
 <EMI ID = 240.1>

  
 <EMI ID = 241.1>

  
 <EMI ID = 242.1>

  
 <EMI ID = 243.1>

  
 <EMI ID = 244.1> propionyl in the above reaction by. propio- chlorides

  
 <EMI ID = 245.1>

  
 <EMI ID = 246.1>

  
 <EMI ID = 247.1>

  
 <EMI ID = 248.1>

  
 <EMI ID = 249.1>

  
 <EMI ID = 250.1>

  
 <EMI ID = 251.1>

  
of Example 2, the corresponding compounds are obtained.

  
 <EMI ID = 252.1>

  
 <EMI ID = 253.1>

  
 <EMI ID = 254.1>

  
 <EMI ID = 255.1>

  
 <EMI ID = 256.1>

  
 <EMI ID = 257.1>

  
reaction at reflux with vigorous stirring for -1 hour.

  
 <EMI ID = 258.1>

  
 <EMI ID = 259.1>

  
 <EMI ID = 260.1>

  
the above reaction with the ketones in Table Hereinafter, the corresponding compounds listed in Table II below are obtained.

  
 <EMI ID = 261.1>

  
 <EMI ID = 262.1>

  
 <EMI ID = 263.1>

  
 <EMI ID = 264.1>

  
 <EMI ID = 265.1>

  
 <EMI ID = 266.1>

  
 <EMI ID = 267.1>

  
 <EMI ID = 268.1>
the mixture is heated to reflux with stirring until .qu'il.

  
 <EMI ID = 269.1>

  
 <EMI ID = 270.1>

  
 <EMI ID = 271.1> <EMI ID = 272.1>

  
 <EMI ID = 273.1>

  
 <EMI ID = 274.1>

  
 <EMI ID = 275.1> <EMI ID = 276.1>

  
 <EMI ID = 277.1>

  
 <EMI ID = 278.1>

  
0. By repeating the above operations by means of the reactions

  
 <EMI ID = 279.1>

  
tie A, we obtain the corresponding compounds.

  
 <EMI ID = 280.1>

  
 <EMI ID = 281.1> <EMI ID = 282.1>

  
 <EMI ID = 283.1>

  
 <EMI ID = 284.1>

  
an ether extraction is carried out. The ethereal extracts are washed

  
 <EMI ID = 285.1>

  
sodium 'and then with brine, after which they are dried on <EMI ID = 286.1>

  
laying.

  
 <EMI ID = 287.1>

  
 <EMI ID = 288.1>

  
 <EMI ID = 289.1>

  
 <EMI ID = 290.1>

  
 <EMI ID = 291.1>

  
water, it is extracted and the extracts are washed. the

  
 <EMI ID = 292.1>

  
EXAMPLE 15.-

  
 <EMI ID = 293.1> <EMI ID = 294.1> <EMI ID = 295.1>

  
 <EMI ID = 296.1> <EMI ID = 297.1>

  
butyric

  
 <EMI ID = 298.1> <EMI ID = 299.1>

  
butyric '<EMI ID = 300.1>

  
'butyric

  
 <EMI ID = 301.1>

  
butyric <EMI ID = 302.1>

  
 <EMI ID = 303.1> <EMI ID = 304.1>

  
136. acid

  
butyric

  
 <EMI ID = 305.1>

  
 <EMI ID = 306.1>

  
butyric

  
 <EMI ID = 307.1> <EMI ID = 308.1>

  
butyric

  
 <EMI ID = 309.1>

  
butyric

  
 <EMI ID = 310.1>

  
 <EMI ID = 311.1> and "allowed to crystallize. The product is separated by filtration, washed with water and recrystallized from benzene.

  
 <EMI ID = 312.1> the corresponding compounds.

  
 <EMI ID = 313.1>

  
 <EMI ID = 314.1>

  
 <EMI ID = 315.1>

  
Mantis and we then add to it, drop by drop sense of agitation,

  
 <EMI ID = 316.1>

  
 <EMI ID = 317.1>

  
 <EMI ID = 318.1>

  
 <EMI ID = 319.1>

  
 <EMI ID = 320.1>

  
 <EMI ID = 321.1>

  
biphenylyl) ethyl lactate ...

  
 <EMI ID = 322.1>

  
 <EMI ID = 323.1>

  
 <EMI ID = 324.1>

  
next bleau.

  
 <EMI ID = 325.1>

  
 <EMI ID = 326.1>

  
ethyl <EMI ID = 327.1>

  
ethyl ..

  
26. ethyl a-methyl-p-i-propylphenylglycolate

  
27. ethyl a-methyl-p-t-butylphenylglycolate

  
 <EMI ID = 328.1> <EMI ID = 329.1> <EMI ID = 330.1>

  
ethyl '/ butyrate

  
 <EMI ID = 331.1>

  
 <EMI ID = 332.1> <EMI ID = 333.1>

  
do for 3 hours 30 minutes. The catalyst is separated by

  
 <EMI ID = 334.1>

  
 <EMI ID = 335.1>

  
correspondents, a representative list of which is given in ta-

  
 <EMI ID = 336.1>

BOARD

  
 <EMI ID = 337.1> <EMI ID = 338.1> <EMI ID = 339.1> <EMI ID = 340.1>

  
 <EMI ID = 341.1>

  
 <EMI ID = 342.1>

  
(0.066 saw) over 5 minutes with concentrated sulfuric acid -, ice cold and stirred (18 µl) while the system is cooled. We add

  
 <EMI ID = 343.1>

  
 <EMI ID = 344.1>

  
Upon addition of the nitric acid, the mixture is stirred for 30 minutes, then poured into water. The mixture is basified with sodium hydroxide and then extracted with ether.

  
 <EMI ID = 345.1>

  
 <EMI ID = 346.1>

  
 <EMI ID = 347.1>

  
 <EMI ID = 348.1>

  
close to neutrality after addition. The pH is then adjusted

  
 <EMI ID = 349.1>

  
 <EMI ID = 350.1>

  
 <EMI ID = 351.1> <EMI ID = 352.1>

  
of the invention.

  
 <EMI ID = 353.1>

  
 <EMI ID = 354.1>

  
carbon in hydrogen under a pressure of 2 atmospheres at

  
 <EMI ID = 355.1>

  
of pyridine. The reaction mixture is stirred overnight

  
 <EMI ID = 356.1>

  
 <EMI ID = 357.1>

  
the catalyst is filtered off and the filtrate is evaporated under - <EMI ID = 358.1> <EMI ID = 359.1>

  
during 30 minutes. The reaction mixture is stirred for

  
 <EMI ID = 360.1>

  
The mixture is then cooled and the toluene is separated off, after which drying is carried out over sodium sulphate and a.

  
 <EMI ID = 361.1>

  
 <EMI ID = 362.1>

  
spontaneous position. After the decomposition, we submit the new

  
 <EMI ID = 363.1> <EMI ID = 364.1>

  
 <EMI ID = 365.1>

  
 <EMI ID = 366.1>

  
 <EMI ID = 367.1>

  
 <EMI ID = 368.1>

  
vention-.

  
 <EMI ID = 369.1>

  
Acid

  
 <EMI ID = 370.1>

  
 <EMI ID = 371.1>

  
 <EMI ID = 372.1>

  
 <EMI ID = 373.1>

  
 <EMI ID = 374.1>

  
 <EMI ID = 375.1>

  
copper bronze with stirring and the mixture is heated slowly

  
 <EMI ID = 376.1>

  
sulfate, then with water, after which it is dried over sodium sulfate and evaporated in vacuo. The residue is crystallized

  
 <EMI ID = 377.1>

  
- The ethyl ester of this acid is formed by reaction of, <EMI ID = 378.1>

  
anhydrous hydrochloric acid.

  
 <EMI ID = 379.1>

  
tîon.

  
 <EMI ID = 380.1>

  
 <EMI ID = 381.1>

  
the ethereal extract with water, with sight. dilute sodium hydroxide solution and with water, then dried over sulfate

  
 <EMI ID = 382.1>

  
 <EMI ID = 383.1>

  
of potassium hydroside. The reaction mixture is heated to

  
 <EMI ID = 384.1>

  
capto-4-biphenylyl) lactic acid.

  
 <EMI ID = 385.1>

  
 <EMI ID = 386.1>

  
to of the invention.

  
 <EMI ID = 387.1>

  
 <EMI ID = 388.1> <EMI ID = 389.1>

  
 <EMI ID = 390.1>

  
 <EMI ID = 391.1>

  
 <EMI ID = 392.1> <EMI ID = 393.1>

  
 <EMI ID = 394.1>

  
 <EMI ID = 395.1>

  
of the invention, the corresponding isomers can be obtained.

  
 <EMI ID = 396.1>

  
 <EMI ID = 397.1> <EMI ID = 398.1> <EMI ID = 399.1>

  
sodium phenylyl) lactate.

  
 <EMI ID = 400.1>

  
 <EMI ID = 401.1>

  
obtains the corresponding salts.

  
sodium hydroxide potassium hydroxide calcium bydroxide potassium carbonate 'magnesium bicarbonate

  
B. Using the various acids of the invention, the corresponding salts can be prepared.

  
 <EMI ID = 402.1>

  
 <EMI ID = 403.1>

  
 <EMI ID = 404.1>

  
 <EMI ID = 405.1>

  
this reaction the corresponding salts.

  
 <EMI ID = 406.1> <EMI ID = 407.1>

  
 <EMI ID = 408.1>

  
 <EMI ID = 409.1>

  
 <EMI ID = 410.1>

  
cold saturated with sodium bicarbonate, then twice: times with ice water at a rate of 250 ml each time. We dry it. ethereal solution over anhydrous sodium sulfate and filtered.

  
 <EMI ID = 411.1>

  
The table below gives a representative list of products

  
 <EMI ID = 412.1>

BOARD

  
 <EMI ID = 413.1> <EMI ID = 414.1>

  
 <EMI ID = 415.1>

  
ethyl <EMI ID = 416.1>

  
63. ethyl a-chloro-p- (2-thienyl) phenylacetate <EMI ID = 417.1> <EMI ID = 418.1>

  
ethyl -

  
 <EMI ID = 419.1> <EMI ID = 420.1>

  
150. Y-chloro-Y- (3-trifluoromethyl-4-cyclohexylphenyl) -

  
ethyl butyrate

  
 <EMI ID = 421.1> <EMI ID = 422.1>

  
 <EMI ID = 423.1>

  
in the above reaction, the corresponding amides are obtained.

  
 <EMI ID = 424.1>

  
These (100 ml in total), then dried over sodium sulfate.

  
 <EMI ID = 425.1> <EMI ID = 426.1>

  
 <EMI ID = 427.1>

  
 <EMI ID = 428.1>

  
 <EMI ID = 429.1>

  
we can., by the. above reaction, prepare the corresponding salts.

  
 <EMI ID = 430.1>

  
 <EMI ID = 431.1>

  
as above, prepare the corresponding compounds.

  
 <EMI ID = 432.1>

  
 <EMI ID = 433.1>

  
 <EMI ID = 434.1>

  
with 70 ml of petroleum ether and the whole is poured into 125 ml of ice water. The organic phase is separated and washed with a

  
 <EMI ID = 435.1>

  
che over anhydrous sodium sulfate and filtered, after which

  
 <EMI ID = 436.1>

  
 <EMI ID = 437.1> corresponding amides.

  
 <EMI ID = 438.1>

  
correspondents.

  
 <EMI ID = 439.1>

  
 <EMI ID = 440.1> <EMI ID = 441.1>

  
The aqueous and glycolic mixture is extracted with ether, then the ethereal extract is dried, evaporated to dryness and distilled.

  
 <EMI ID = 442.1>

  
ethyl pionate.

  
A. By repeating the above operations using the various bromoalkanoates and bromoalkanoamides of the invention, the corresponding fluoroalkanoates and fluoroalkanoamides are obtained.

  
 <EMI ID = 443.1>

  
By hydrolyzing the fluoroalkanoates of Example 51,

  
 <EMI ID = 444.1>

  
correspondents.

  
 <EMI ID = 445.1>

  
 <EMI ID = 446.1>

  
 <EMI ID = 447.1>

  
fluoroalkanoic acids.

  
 <EMI ID = 448.1>

  
 <EMI ID = 449.1>

  
 <EMI ID = 450.1>

  
anhydrous. The reaction mixture is evaporated to dryness and the mixture is extracted.

  
 <EMI ID = 451.1>

  
 <EMI ID = 452.1>

  
A. By carrying out the above operations by means of the bromoalkanoates and bromoalcanoamides of the invention, the corresponding iodoalkanoates and iodoalkanoamides are obtained.

  
EXAMPLE 55.-

  
 <EMI ID = 453.1>

  
 <EMI ID = 454.1>

  
laying.

  
EXAMPLE 56 .--

  
By reacting iodoalkahoic acids as in

  
 <EMI ID = 455.1>

  
noics.

  
EXAMPLE 57. -

  
 <EMI ID = 456.1> that (0.05 mol) and 5 g of sodium hydrosulfide in 100 ni

  
 <EMI ID = 457.1>

  
 <EMI ID = 458.1>

  
extract the residue with ether, then the extract is washed with water and with saturated sodium chloride solution, after which it is dried and evaporated to dryness to obtain α-mercap acid -

  
 <EMI ID = 459.1>

  
A. Carrying out the above reaction with the acids chlo-

  
 <EMI ID = 460.1>

  
 <EMI ID = 461.1>

  
 <EMI ID = 462.1>

  
 <EMI ID = 463.1>

  
in 60 ml of dry tetrahydrofuran. The mixture is heated under reflux for 3 hours, then stirred at room temperature.

  
 <EMI ID = 464.1>

  
 <EMI ID = 465.1>

  
the residue is extracted with ether, then the ethereal extract is washed with water and with saturated sodium chloride solution, after which it is dried and evaporated to dryness to obtain

  
 <EMI ID = 466.1>

  
A. Carrying out the above reaction using chloroalkanoic acids, chloroalkanoates and chloroalkanoamides

  
 <EMI ID = 467.1>

  
methylthioalkanoates and the corresponding methylthioalkanoamides.

  
 <EMI ID = 468.1>

  
 <EMI ID = 469.1>

  
 <EMI ID = 470.1>

  
to a solution of 600 ml of anhydrous ethanol and 21 g of potassium hydroxide (0.317 mol). 79 g of acid are added to the mixture

  
 <EMI ID = 471.1>

  
follows agitation for 15 hours. The solid which forms is collected by filtration and washed with ethanol. The filtrate is evaporated to dryness and the residue is dissolved in 500 ml of ether, then the ethereal solution is washed several times with water. By drying the ethereal solution and evaporating it - <EMI ID = 472.1> <EMI ID = 473.1> <EMI ID = 474.1>

  
hours, then the solvent is removed therefrom, the residue is dissolved in ether, the mixture is filtered and the ethereal solution is washed with cold water. The ethereal solution is dried over magnesium sulfate and then evaporated to dryness to give 1-1-acid.

  
 <EMI ID = 475.1>

  
dants.

  
EXAMPLE 61.-

  
 <EMI ID = 476.1>

  
 <EMI ID = 477.1>

  
 <EMI ID = 478.1>

  
 <EMI ID = 479.1>

  
 <EMI ID = 480.1>

  
 <EMI ID = 481.1> <EMI ID = 482.1>

  
 <EMI ID = 483.1>

  
 <EMI ID = 484.1>

  
 <EMI ID = 485.1>

  
 <EMI ID = 486.1>

  
rée and 1 * evaporated to dryness to obtain the acid a-thiocyanato-

  
 <EMI ID = 487.1>

  
sodium nate (0.1 mol) to a solution of 0.12 sole of sulphite:

  
 <EMI ID = 488.1>

  
reaction for 15 hours, then filtered and washed

  
 <EMI ID = 489.1>

  
 <EMI ID = 490.1>

  
ethyl nate

  
A mixture of

  
 <EMI ID = 491.1>

  
(0.023 mol) and 5.7 g of sodium thiosulfate pentahydrate

  
 <EMI ID = 492.1>

  
 <EMI ID = 493.1>

  
continue heating at reflux for 30 minutes. The reaction mixture is then evaporated to dryness in vacuo, followed by

  
azeotropic distillation with ethanol and evaporated

  
again the liquid phase to dryness under vacuum. The residue is triturated in ether, the mixture is filtered and the solution evaporated to dryness. The residue is triturated again with hexane and the resulting gum is dissolved in alcohol, then the solution is evaporated to dryness in vacuo to obtain the sodium salt.

  
 <EMI ID = 494.1>

  
A. By carrying out the above reaction by means of the chloroalkanoates and chloroalkanoamides of the invention, the corresponding thiosulfoalkanoates and thiosulfoalkanoamides are obtained. EXAMPLE 6? .-

  
 <EMI ID = 495.1>

  
their esters and amides of the invention in the above reactions; the amidinoalkanoic acids are obtained as well as the corresponding esters and amides.

  
 <EMI ID = 496.1>

  
fuck.

  
36.3 g of potassium ethyl xanthate (0.22 mol) are dissolved in 150 ml of absolute ethanol by stirring. We add to the

  
 <EMI ID = 497.1>

  
 <EMI ID = 498.1> <EMI ID = 499.1>

  
 <EMI ID = 500.1>

  
 <EMI ID = 501.1>

  
 <EMI ID = 502.1>

  
 <EMI ID = 503.1>

  
 <EMI ID = 504.1>

  
above process with carbayl chloride (prepared in situ

  
 <EMI ID = 505.1>

  
 <EMI ID = 506.1> .ters and corresponding amides.

  
EXAMPLE 69.-

  
 <EMI ID = 507.1>

  
fuck.

Claims (1)

<EMI ID=508.1> <EMI ID = 508.1> <EMI ID=509.1> <EMI ID = 509.1> <EMI ID=510.1> <EMI ID = 510.1> <EMI ID=511.1> <EMI ID = 511.1> <EMI ID=512.1> <EMI ID = 512.1> <EMI ID=513.1> <EMI ID = 513.1> <EMI ID=514.1> <EMI ID = 514.1> <EMI ID=515.1> <EMI ID = 515.1> dical ammonium); dical ammonium); <EMI ID=516.1> <EMI ID = 516.1> sente pas un radical alcoyle inférieur" does not smell a lower alkyl radical " <EMI ID=517.1> <EMI ID = 517.1> <EMI ID=518.1> <EMI ID = 518.1> <EMI ID=519.1> <EMI ID = 519.1> <EMI ID=520.1> d'halogénation capable de remplacer le radical hydroxyle par un _atome d'halogène et, si on le désire, on désestérifie 11 ester <EMI ID = 520.1> halogenation capable of replacing the hydroxyl radical with a halogen atom and, if desired, deesterification of the ester <EMI ID=521.1> <EMI ID = 521.1> azotée de formule Z-H pour obtenir l'amide d'acide- génoalcanoïque.. nitrogenous of formula Z-H to obtain the amide of genoalkanoic acid. 2.- Procédé suivant la revendication 1, caractérisé en ce que l'agent d'halogénation est choisi parmi les halogénures de thionyle, les halogénures de sulfuryle, les halogénures de soufre, les trihalogénures de phosphore, les oxyhalogénures de phosphore et les pentahalogénures de phosphore. 2. A method according to claim 1, characterized in that the halogenating agent is chosen from thionyl halides, sulfuryl halides, sulfur halides, phosphorus trihalides, phosphorus oxyhalides and pentahalides of phosphorus. 3.- Procédé suivant la revendication 1 ou 2, caractérisé en ce qu'on exécute la désestérification au moyen d'acide acé- 3. A method according to claim 1 or 2, characterized in that the deesterification is carried out by means of ac- <EMI ID=522.1> <EMI ID = 522.1> halogénoalcanoique suivant la revendication 1 et de ses dérivés, caractérisé en ce qu'on fait réagir un sulfonate d'un acide.phé- haloalkanoic acid according to Claim 1 and its derivatives, characterized in that a sulfonate of an acid is reacted. <EMI ID=523.1> <EMI ID = 523.1> ou d'amide,-répondant à la formule : or amide, corresponding to the formula: <EMI ID=524.1> <EMI ID = 524.1> <EMI ID=525.1> <EMI ID = 525.1> et les autres symboles ont les significations qui leur ont été données dans la revendication 1, avec un halogénure métallique capable de remplacer le radical sulfonyloxy par un atome d'halogène . and the other symbols have the meanings given to them in claim 1, with a metal halide capable of replacing the sulfonyloxy radical with a halogen atom. <EMI ID=526.1> <EMI ID = 526.1> ce que l'halogénure métallique est un halogénure de métal alcalin. that the metal halide is an alkali metal halide. 6.- Procédé suivant l'une quelconque des revendications 6.- A method according to any one of claims <EMI ID=527.1> <EMI ID = 527.1> <EMI ID=528.1> <EMI ID = 528.1> d'ammonium ou en sel d'aminé de l'acide. ammonium or amine salt of the acid. 7.- Procédé de préparation d'un acide phényl(substitué)- 7.- Process for preparing a phenyl acid (substituted) - <EMI ID=529.1> <EMI ID=530.1> <EMI ID = 529.1> <EMI ID = 530.1> <EMI ID=531.1> <EMI ID = 531.1> <EMI ID=532.1> <EMI ID = 532.1> <EMI ID=533.1> <EMI ID = 533.1> <EMI ID=534.1> <EMI ID = 534.1> <EMI ID=535.1> <EMI ID=536.1> <EMI ID = 535.1> <EMI ID = 536.1> <EMI ID=537.1> <EMI ID = 537.1> et? si on-le désire <EMI ID=538.1> <EMI ID=539.1> and? if desired <EMI ID = 538.1> <EMI ID = 539.1> <EMI ID=540.1> <EMI ID = 540.1> <EMI ID=541.1> <EMI ID = 541.1> et :Les autres symboles ont les significations qui leur ont été and: The other symbols have their meanings <EMI ID=542.1> <EMI ID = 542.1> <EMI ID=543.1> <EMI ID = 543.1> <EMI ID=544.1> <EMI ID = 544.1> <EMI ID=545.1> <EMI ID = 545.1> <EMI ID=546.1> <EMI ID=547.1> <EMI ID = 546.1> <EMI ID = 547.1> <EMI ID=548.1> <EMI ID = 548.1> <EMI ID=549.1> <EMI ID = 549.1> <EMI ID=550.1> <EMI ID = 550.1> <EMI ID=551.1> <EMI ID = 551.1> <EMI ID=552.1> <EMI ID = 552.1> <EMI ID=553.1> <EMI ID = 553.1> <EMI ID=554.1> <EMI ID = 554.1> <EMI ID=555.1> <EMI ID = 555.1> <EMI ID=556.1> <EMI ID=557.1> <EMI ID=558.1> <EMI ID = 556.1> <EMI ID = 557.1> <EMI ID = 558.1> en présence d'une amine tertiaire. in the presence of a tertiary amine. 10.- Procédé suivant la revendication 9, caractérisé en ce que l'halogénure d'acide ou 1* anhydride est choisi parmi le chlorure d'acétyle, l'anhydride acétique, le chlorure de propionyle, le chlorure de butyryle, l'anhydride succinique, l'anhydride maléique, l'anhydride phtalique, le chlorure de benzoyle, l'anhydride benzoïque, le chlorocarbonate de benzyle, le chlorocarbo- 10. A method according to claim 9, characterized in that the acid halide or 1 * anhydride is selected from acetyl chloride, acetic anhydride, propionyl chloride, butyryl chloride, anhydride succinic, maleic anhydride, phthalic anhydride, benzoyl chloride, benzoic anhydride, benzyl chlorocarbonate, chlorocarbon <EMI ID=559.1> <EMI ID = 559.1> dibutylcarbamyle, le chlorure de benzènesulfonyle et le chlorure de méthanesulfonyle. dibutylcarbamyl, benzenesulfonyl chloride and methanesulfonyl chloride. 11.- Nouveaux composés de formule générale : 11.- New compounds of general formula: <EMI ID=560.1> <EMI ID = 560.1> <EMI ID=561.1> <EMI ID = 561.1> aryloxy, arylthio, arylamino, aroyle, hétérocyclique. aryle ou aryle portant un substituant symbolisé par Y ; Y représente un atome d'hydrogène ou d'halogène ou un radical aryloxy, arylthio, arylamino, aroyl, heterocyclic. aryl or aryl carrying a substituent symbolized by Y; Y represents a hydrogen or halogen atom or a radical alcoyle, nitro, amino, acylamino, monoalcoyl(inférieur)-amino, dialcoyl(inférieur)-amino, mercapto, acylthio, alcoyl- (inférieur)-thio, alcoyl(inférieur)-sulfinyle, alcoyl(inférieur)-sulfonyle, hydroxyle, alcoyloxy inférieur, acyloxy, halogénoalcoyle inférieur, cyano ou acétyle; alkyl, nitro, amino, acylamino, monoalkyl (lower) -amino, dialkoyl (lower) -amino, mercapto, acylthio, alkyl- (lower) -thio, (lower) alkyl -sulfinyl, (lower) alkyl -sulfonyl, hydroxyl, lower alkyloxy, acyloxy, lower haloalkyl, cyano or acetyl; n a une valeur de 0 à 2; n has a value of 0 to 2; m a une valeur de 0 à 2; m is 0 to 2; la somme de n et de m a.une valeur de 0 à 2; the sum of n and m has a value of 0 to 2; <EMI ID=562.1> <EMI ID = 562.1> caux alcoyle inférieurs; lower alkyl calluses; X représente un atome d'halogène ou un radical hydroxyle, alcoy loxy inférieur, acyloxy inférieur, aroyloxy, carboalcoyloxy (inférieur), carbamyloxy, alcoyl(inférieur)-carbamyloxy, dialcoyl(inférieur)-carbamyloxy, alcane(inférieur)-sulfonyl- <EMI ID=563.1> X represents a halogen atom or a hydroxyl radical, lower alkyloxy, lower acyloxy, aroyloxy, carboalkyloxy (lower), carbamyloxy, alkyl (lower) -carbamyloxy, dialkoyl (lower) -carbamyloxy, alkane (lower) -sulfonyl- < EMI ID = 563.1> <EMI ID=564.1> <EMI ID=565.1> <EMI ID = 564.1> <EMI ID = 565.1> <EMI ID=566.1> <EMI ID=567.1> <EMI ID = 566.1> <EMI ID = 567.1> <EMI ID=568.1> <EMI ID = 568.1>
BE776316A 1971-03-10 1971-12-06 Phenylacetic acid derivs - as antiinflammatory agents BE776316R (en)

Applications Claiming Priority (9)

Application Number Priority Date Filing Date Title
US12299871A 1971-03-10 1971-03-10
US15236871A 1971-06-11 1971-06-11
US00152366A US3821268A (en) 1970-05-05 1971-06-11 Alpha-acylthio biphenylylacetic acids
US00152387A US3852323A (en) 1970-05-05 1971-06-11 Phenylacetic acids
US00152451A US3821267A (en) 1970-05-05 1971-06-11 A-acylthio-p-cyclohexylphenylacetic acid and derivatives
US16482271A 1971-07-21 1971-07-21
US16492071A 1971-07-21 1971-07-21
BE773385A BE773385A (en) 1971-09-30 1971-09-30 Phenylacetic acid derivs - anti-inflammatory antipyretic analgesic agents
US195825A US3867434A (en) 1971-11-04 1971-11-04 Phenyl butyric acids and derivatives thereof

Publications (1)

Publication Number Publication Date
BE776316R true BE776316R (en) 1972-06-06

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BE776316A BE776316R (en) 1971-03-10 1971-12-06 Phenylacetic acid derivs - as antiinflammatory agents

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Country Link
BE (1) BE776316R (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2196167A1 (en) * 1972-08-17 1974-03-15 Thomae Gmbh Dr K

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2196167A1 (en) * 1972-08-17 1974-03-15 Thomae Gmbh Dr K
FR2196168A1 (en) * 1972-08-17 1974-03-15 Thomae Gmbh Dr K

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