CH413856A - Process for the preparation of therapeutic compounds - Google Patents

Process for the preparation of therapeutic compounds

Info

Publication number
CH413856A
CH413856A CH7342559A CH7342559A CH413856A CH 413856 A CH413856 A CH 413856A CH 7342559 A CH7342559 A CH 7342559A CH 7342559 A CH7342559 A CH 7342559A CH 413856 A CH413856 A CH 413856A
Authority
CH
Switzerland
Prior art keywords
sep
lower alkyl
carbon atoms
group
radical
Prior art date
Application number
CH7342559A
Other languages
French (fr)
Inventor
Malcolm Bloom Barry
Edward Carnahan Robert
Original Assignee
Pfizer & Co C
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 US784083A external-priority patent/US2894972A/en
Application filed by Pfizer & Co C filed Critical Pfizer & Co C
Publication of CH413856A publication Critical patent/CH413856A/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C243/00—Compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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
    • C07D207/325—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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 with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/46—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
    • C07D207/50—Nitrogen 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
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/86—Hydrazides; Thio or imino analogues thereof
    • 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
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/86—Hydrazides; Thio or imino analogues thereof
    • C07D213/87—Hydrazides; Thio or imino analogues thereof in position 3
    • 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
    • C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
    • C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
    • C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having 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
    • C07D237/22—Nitrogen and oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom 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
    • C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur 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
    • C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pyridine Compounds (AREA)

Description

  

  



  Procédé de préparation de composés thérapeutiques
 L'invention est relative à la préparation de nouveaux composés qui sont d'intéressants agents   théra-    peutiques, applicables en vue du traitement de maladies mentales et communément dénommés psychotoniques.



   Les nouveaux composés, dont la préparation constitue l'objet de l'invention, peuvent être représentés par la formule générale suivante :
EMI1.1     
 (formule 1) dans laquelle A est de l'hydrogène ou un groupe acyle de formule RCO-dans laquelle R est un radical alcoyle ou alcényle qui contient au plus 20 atomes de carbone et est éventuellement substitué par de l'halogène ou un ou des restes amino, alcoylamino (avec alcoyle inférieur), hydroxy, alcoxy inférieur, mercapto,   alcoyl-mercapto    (avec alcoyle inférieur), alcanoylamino, alcanoyl-oxy ou alcanoylmercapto, dans lesquels le groupe alcanoyl contient de 2 à 4 atomes de carbone ;

   ou un groupe   E-(CHg) S-, où   
E est un reste cycloalcoyle contenant de 3 à 6 atomes de carbone ou un groupe pyridyle, furyle,   thiényle,    thiazolyle, oxazolyle, isoxazolyle éventuellement substitués dans le noyau, et m est un nombre entier de 0 à   4 ;    ou un groupe
EMI1.2     
 dans laquelle X est de l'hydrogène, un radical alcoyle inférieur ou un halogène, Y est de l'hydrogène, un radical alcoyle inférieur, alcoxy inférieur, un halogène, un radical trifluorométhyl, cyano ou un alcanoyl contenant de 2 à 4 atomes de carbone, et n est un nombre entier de 0 à 4 ; 3 est un radical alcoylène comprenant une chaîne droite de 1 à 5 atomes de carbone ;

   Ri est un atome d'hydrogène ou un radical alcoyle inférieur ;   R2    est un radical alcoyle,   alcényle    ou cycloalcoyle contenant de 3 à 6 atomes de carbone ou un groupe pyridyle, pyridylalcoyle, furylalcoyle ou thiénylalcoyle, le radical alcoyle de ces derniers étant un radical alcoyle inférieur, et dans lesquels groupes le noyau peut porter un radical alcoyle inférieur, ou un groupe
EMI1.3     
 dans laquelle X, Y et n ont la signification donnée plus haut.



   L'invention porte également sur la préparation des sels d'addition acides des composés azotés basiques décrits.



   Les radicaux alcoylène représentés par Z sont   dé-    rivés de groupes aliphatiques en chaîne droite ou en chaîne ramifiée, et ils contiennent de 1 à 5 atomes de carbone dans leur chaîne principale.



   Les divers radicaux hydrocarbures décrits peuvent à leur tour être substitués par les divers substituants précédemment mentionnés. Particulièrement intéressants sont les composés correspondant à la formule :
EMI2.1     
 dans lesquels R2 est un groupe
EMI2.2     

De plus, ceux des composés dans lesquels RCO provient d'un aminoacide possèdent des   propriétés thé-    rapeutiques souhaitables. Les nouveaux composés selon l'invention sont préparés par la réaction d'une amine de formule   NHRtRa    avec un acide de formule ANHNHZCOOH ou un dérivé approprié dudit acide tel qu'un ester d'alcoyle inférieur de formule   ANHNHZCOOR4    dans laquelle R4 est un radical alcoyle contenant de préférence de 1 à 3 atomes de carbone.

   D'autres dérivés d'acides susceptibles d'etre utilisés sont les halogénures et les anhydrides d'acides. Il va de soi, comme le comprendra immédiatement l'homme de l'art, que l'on doit soigneusement veiller à minimiser les réactions parasites qui sont susceptibles de se produire lorsqu'on utilise de tels dérivés acides, qui sont   d : fonctionnels,    en raison de la présence de la fraction hydrazine de la molécule.

   Bien que la réaction puisse être provoquée en mélangeant tout simplement l'amine choisie avec 1'ester d'alcoyl ou tout autre dérivé décrit plus haut, et en abandonnant le mélange au repos à la température ambiante ordinaire (environ   200)    pendant un laps de temps compris entre environ un et environ trois jours, on préfère généralement chauffer le   me-    lange réactionnel à une température comprise entre environ 60 et environ 2000, étant donné que ce mode opératoire permet d'abréger considérablement le temps de réaction. C'est ainsi, par exemple, que l'on peut constater l'obtention d'un excellent rendement de produit lorsque la réaction est effectuée à environ   1300    pendant un temps compris entre 2 et 4 heures.



  On utilise généralement les réactifs en concentrations molaires égales, bien que le procédé selon l'invention soit avantageusement mis en oeuvre avec un léger excès molaire (jusqu'à   10 0/0) d'amine.    L'utilisation d'un gros excès ne conduit à aucun avantage notable et n'est pas avantageux. Une fois la réaction terminée, la masse réactionnelle refroidie est recristallisée dans un solvant approprié, tel que acétate d'éthyle, alcanols inférieurs tels que méthanol, éthanol, propanol, etc., et analogues.



   Les nouveaux agents thérapeutiques préparés selon l'invention possèdent une activité, dans le traitement des dépressions mentales, considérablement supérieure à celle des agents connus dans l'art antérieur. En outre, les nouveaux agents possèdent un        indice thérapeutique)    >     supérieur à celui des agents antérieurement connus. L'indice thérapeutique signifie, dans l'acception utilisée dans la présente description, le rapport de l'activité thérapeutique à la toxicité.



  L'utilisation en vue du traitement de la dépression mentale, de nombreux agents connus dans l'art antérieur, s'accompagne chez le patient de réactions toxiques considérables. Le rapport de l'activité à la toxicité d'un agent thérapeutique est évidemment des plus importants dans le choix d'un tel agent. Bien que de nombreux agents soient dotés d'une activité thérapeutique tout à fait remarquable, leur utilisation se trouve considérablement entravée du fait d'une toxicité excessive. Ces agents thérapeutiques, en raison de leur indice thérapeutique très élevé, sont plus intéressants que les agents antérieurement connus pour le traitement de la dépression mentale.

   Ces nouveaux agents thérapeutiques, dans lesquels R est un radical pyridine, possèdent en outre une activité antituberculeuse appréciable, tandis que ceux dans lesquels R est un radical benzène,   thiophène    ou furane, ne   possè-    dent pas cette dernière activité.



   Le médecin prescrira les doses quotidiennes de ces agents thérapeutiques qu'il s'agit d'utiliser. La posologie dépendra du degré de dépression mentale, suivant qu'elle est bénigne ou grave. Si elle est bénigne, on peut prescrire une dose de 10 à   50 mg par    jour. Pour une dépression grave, des doses quotidien  nes considérablement    plus élevées peuvent être   né-    cessaires et il est, par exemple, possible de prescrire jusqu'à 150 mg, voire même plus. Des comprimés ou capsules dosés à   10,    25, 50 et   150 mg    des nouveaux agents thérapeutiques constituent des modes de présentation adéquats en vue de l'administration quotidienne.

   De tels comprimés ou capsules peuvent être préparés à partir de mélanges de ces composés avec des excipients pharmaceutiques bien connus tels qu'amidon, sucre, tapioca, certaines formes d'argile et analogues. A titre de variante, il est possible de constituer des préparations liquides à partir de mélanges de ces agents thérapeutiques et de milieux liquides   pharmaceutiquement    acceptables tels que eau, glycols aqueux, solutions sucrées et analogues qui peuvent contenir des agents aromatisants et colorants classiques.



   Etant donné qu'un grand nombre de ces composés sont basiques, il est possible de tirer avantage de la solubilité dans   l'eau    de sels que ces composés forment avec des acides, pour procéder à l'isolement et/ou à la purification des susdits composés et à la préparation de solutions aqueuses de ces nouveaux composés en vue de leur administration par voie orale ou parentérale. Il va de soi que seuls les sels formés à partir d'acides pharmaceutiquement acceptables peuvent être utilisés en vue   d'applications thé-    rapeutiques. Des sels particulièrement efficaces sont ceux formés avec des acides   pharmaceutiquement      ac-    ceptables possédant une valeur de pK inférieure ou au plus égale à 3. De tels acides sont bien connus dans l'art.

   Ce sont, par exemple, les acides chlorhydrique, bromhydrique, nitrique, phosphorique, benzènesulfonique, toluènesulfonique,   méthylsulfoni-    que, éthylsulfonique et analogues. Ces sels peuvent être préparés par les modes opératoires habituellement utilisés dans   l'art    et consistant, par exemple, à faire réagir le composé avec un équivalent de l'acide choisi en solution aqueuse, puis à concentrer la solution. Il est également possible d'utiliser d'autres modes opératoires connus.



      Exerraple 1   
 N-henzyl- propionamide
 Une suspension de 7, 5 g (0, 034 mole) de   1-isonico-      tinyl-2-(carbométhoxyéthyl)    hydrazine et de   5 ml    de benzylamine est chauffée tout en agitant à   1300    pendant 3 heures. La masse refroidie est alors   recristalli-    sée dans l'acétate d'éthyle pour donner des aiguilles blanches fondant à 151, 1-152, 1 . L'analyse élémentaire donne les résultats suivants :
 Calculé pour C10H18N4O :
   C=64,    43 ; H=6,   07 ; N=18,    77
 Trouvé :   C=64,    43 ; H=6, 27 :   N=19,    17.



   Exemple 2
 N-benzyl-ss-(benzoylhydrazino)propionamide
 Ce composé est préparé par le mode opératoire de 1'exemple 1 en utilisant de la   1-benzoyl-2- (carbo-      éthoxyéthyl)    hydrazine à la place du composé d'isonicotinyl correspondant. Le produit fond à 164-165 .



  L'analyse élémentaire est en bon accord avec les valeurs calculées.



   Exemple 3    N-(p-chlorobenzyl)-(ss-isonicotinylhydrazino)-   
 propionamide
 On reprend le mode opératoire de 1'exemple 1 en utilisant la p-chlorobenzylamine à la place de la benzylamine. Le produit fond à 162-163 .



   Exemple 4    N-(4-picolyl)-ss-(benzoylhydrazine) propionamide   
 Ce composé est préparé par le mode opératoire de 1'exemple 1 en utilisant de la 4-picolylamine et de la   l-benzoyl-2-(carbométhoxyéthyl)    hydrazine. Le produit fond à   125-127 .    D'autres   p- (acylhydrazino)    propionamides N-substitués, préparés en utilisant des l-acyl-2-(carboalcoxyéthyl) hydrazines adéquates et des amènes appropriées sont :   N-benzyl-p- (2-furoylhydrazine)    propionamide
 (P. F.   183-184 )      N-furfuryl-p- (isonicotinylhydrazine) propionamide   
 (P. F.   129-1310)      N-phényléthyl-p- (isonicotinylhydrazine)    propionamide
 (P.

   F. 145-147 )
N-(3,4-diméthoxyphényléthyl)-ss-(isonicotinylhydra
 zine) propionamide (P. F.   110-114 )      N- (3-méthylbenzyl-p- (isonicotinylhydrazine)    propion
 amide   (. P.    F. 114-116 )
N-   (4-méthylbenzyl)-p-isonicotinylhydrazine) propion-   
 amide (P. F.   133-1350)      N- (2-chlorobenzyl)-p- (isonicotinylhydrazine)    propion
 amide (P. F.   148-1490)      N-(2-méthylbenzyl)-ss-(isonicotinylhydrazine)    propion
 amide (P. F.   148-149 )   
N-(3,4-dichlorobenzyl)-ss-(isonicotinylhydrazine)pro
 pionamide (P. F. 139-140 )   N- (2, 4-dichlorobenzyl)-p- (isonicotinylhydrazine)    pro
 pionamide (P.

   F.   137-139o)   
N-benzyl-ss-(nictinylhydraizne)propionamide
 (P. F.   125-1260)      N-benzyl-p- (cyclohexylcarbohydrazine)    propionamide
 (P. F.   150-1520)      N-méthyl-p- (isonicotinylhydrazine)    propionamide
 (P. F.   119 )      N-éthyl-ss-(isonicotinylhydrazine)    propionamide
 (P. F. 131-132 )
N-n-propyl-ss-(isonictinylhydrazine) propionamide
 (P. F. 118-120 )   N-i-propyl-p- (isonicotinylhydrazine)    propionamide
 (P. F.   163-165 )      N-n-butyl-p- (isonicotinylhydrazine) propionamide   
 (P. F.   120-122 )      N-i-butyl-p- (isonicotinylhydrazine) propionamide   
 (P.

   F.   146-147 )   
N-cyclohexyl-p- (isonicotinylhydrazine) propionamide
 (P. F. 166-167 )   N-allyl-ss-(isonicotinylhydrazine) propionamide   
 (P. F. 117-119 )   N-phénétyl-p- (isonicotinylhydrazine) propionamide   
 (P. F. 145-147 )   
N-benzyl-p- (3-chlorobenzoylhydrazine) propionamide   
 (P. F.   151-153 )      
N-benzyl-ss-(4-fluorobenzoylhydrazine) propionamide   
 (P. F.   214-216 )   
 Exemple   5       N-benzyl-a-hydrazinoacetamide   
 Ce composé est préparé par le mode opératoire de l'exemple 1 en utilisant de la benzylamine et de   1'a-hydrazine-acétate    de méthyle.



   De même, d'autres hydrazinealcanoamides Nsubstitués sont préparés d'une manière similaire en utilisant des amines adéquates. On obtient ainsi :   N-méthyl-N-benzyl-a-hydrazineacétamide
N-pyridyl-a.-hydrazineacétamide
N-n-propyl-α-hydrazineacétamide
N- (p-chlorbenzyl)-a-hydrazineacétamide
N-(2-furfuryl)-a-hydrazineacétamide
N- (allyl)-a-hydrazineacétamide
N-benzyl-p-hydrazinepropionamide
N-allyl-p-hydrazinepropionamide
N-n-propyl-e-hydrazinehexaneamide
N-cyclobutyl-α-hydrazineacétamide
N-pentényl-a-hydrazinepropionamide
N-cyclohexyl-N-méthyl-p-hydrazinebutyramide
N-phénétyl-α

  -hydrazineacétamide
N-4-chlorobenzyl-p-hydrazinepropionamide
N-4-fluorobenzyl-a-hydrazinepropionamide
N-4-méthylbenzyl-a-hydrazinepropionamide   
N-3,   4-dichlorobenzyl-a-hydrazinepropionamide   
N-2, 4-dibromobenzyl-a-hydrazinepropionamide   
N-4-iodobenzyl-p-hydrazinepropionamide
N-3-méthylbenzyl-p-hydrazinepropionamide
N-4-propylphényl-p-hydrazinepropionamide
N-phényl-p-hydrazinepropionamide
N-furfuryl-p-hydrazinepropionamide
N-thiénylméthyl-p-hydrazinepropionamide   
N-2-méthylfurfuryl-ss-hydrzinepropionamide   
N-2-pyridyl-p-hydrazinepropionamide
N-3-pyridyl-p-hydrazmepropionamide
N-2-pyridylpropyl-p-hydrazinepropionamide
N-2-furfurylpropyl-p-hydrazinepropionamide
N- (3, 4-diméthoxybenzyl)-p-hydrazinepropionamide   
N-(4-trifluorométhylbenzyl)

  -ss-hydrazinpropion
 amide   
N- (3-acétylphényl)-p-hydrazinepropionamide
N- (4-butyrylphénylbutyl)-p-hydrazinepropionamide
N-(4-bromophényl)-#-hydrazinebutyramide   
N-(3,4-dipropoxybenzyl)-ss-hydrazineptropionamide   
N- (4-méthoxyphényl)-p-hydrazinepropionamide
N- (6-éthyl-2-pyridyl)-p-hydrazinepropionamide   
N-(4-éthylbenzyl)-ss-hydrazinepropionamide
 Exemple 6
 On prépare un certain nombre d'acylhydrazin  alcanolamines    N-substituées en utilisant le mode   opé-    ratoire de l'exemple   1    et en partant de l'acyl-2- (carboalcoxyalcoyl) hydrazines adéquates et d'amines   appro-    priées.



   Le tableau I donne la liste de tels composés avec les hydrazines substituées correspondantes à partir desquelles ils sont obtenus avec R1R2NH.
EMI4.1     





  Ri <SEP> Tableati <SEP> I
<tb> RCONHNHZCON <SEP> RCONHNHZCOOR4
<tb> R2
<tb> R <SEP> R <SEP> ; <SEP> z <SEP> RS
<tb> C, <SEP> ; <SEP> HÏ-H <SEP> ¯- <SEP> (CH) <SEP> 2-pBrC, <SEP> jH4CH2-C < H6CONHNHCH2CH2COOCH <SEP> s
<tb> 2- <SEP> (CsH4N)-CH <SEP> 3--CH <SEP> (CH3) <SEP> cH2-pIC, <SEP> jH <SEP> CHw-2- <SEP> (CÏH, <SEP> ; <SEP> N) <SEP> CONHNHCH <SEP> (CH3) <SEP> CH2COOCH <SEP> : <SEP> j
<tb> 3- <SEP> (CsH. <SEP> N)-H-- <SEP> (CHs),-pFCt. <SEP> H. <SEP> jCHa- <SEP> 3- <SEP> (C5HN) <SEP> CONHNH <SEP> (CH2) <SEP> ÏCOOc2H 
<tb> QH,-CH,--CH <SEP> (CH,) <SEP> CHa-6-CH <SEP> (CsHgN) <SEP> CH2- <SEP> QH5CONHNHCH <SEP> (QHg) <SEP> CHaCOOCgH,
<tb> 4-{C6HIN)-H--(cH2) <SEP> ;-pC2HÏOCtiH4CH2-4-(CÏH4N) <SEP> CONHNH <SEP> (CH2) <SEP> 3COOC3H7
<tb> CjH  <SEP> CH, <SEP> ;--CH <SEP> (CH3) <SEP> CH <SEP> (CH <SEP> :

   <SEP> ;)-pCHsOCeH. <SEP> tCHa- <SEP> CH5CONHNHCH <SEP> (CH) <SEP> CH <SEP> (CH3) <SEP> COOCH <SEP> ; <SEP> ;
<tb> 4-(C5H4N)-CH. <SEP> ;--CH <SEP> (CH3) <SEP> CH <SEP> (C2Hg)-pC3H70CrjH <SEP> CH2¯ <SEP> 4-(CsH4N) <SEP> CONHNHCH <SEP> (CH3) <SEP> CH <SEP> (CoH3) <SEP> C, <SEP> OOCoH, <SEP> ;
<tb> CfjH3-C <SEP> H7--CH <SEP> (C, <SEP> 3H7) <SEP> CHw-CaH3CaH4-CfiH3CoNHNHCH <SEP> (C3H7) <SEP> CH2COOC2HÏ
<tb> 4- <SEP> (CgHN)-H-- <SEP> (CHa) <SEP> -C, <SEP> jHgC- <SEP> 4- <SEP> (CgH) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> 2- <SEP> (CO)-H-- <SEP> (CHa) <SEP> a-2- <SEP> (CgH. <SEP> tN) <SEP> CHg- <SEP> 2- <SEP> (CO) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCH <SEP> ;

  
<tb> 4- <SEP> (c6H4N)-H-- <SEP> (CHW,),-2-(C6HlN) <SEP> C, <SEP> H,-4-(CÏH4N) <SEP> CONHNHCH2CH2COOCBHÏ
<tb> 3- <SEP> (C4H30)-CH <SEP> 3--CH2CH <SEP> (CH3)- <SEP> (c4Ht3o) <SEP> cH2-3- <SEP> (C4H30) <SEP> CONHNHCH2CH <SEP> (CH3) <SEP> COOCH, <SEP> ;
<tb>  
EMI5.1     


Rl <SEP> Tableall <SEP> I <SEP> (suite)
<tb> RCONHNHZCON <SEP> RCONHNHZCOOR4
<tb> R
<tb> R2
<tb> R <SEP> R, <SEP> z <SEP> R2
<tb> R <SEP> RI <SEP> Z <SEP> R2
<tb> CGH6-H--CH2CH <SEP> (CH3)- <SEP> (C4H3O) <SEP> C2H4-C6H6CONHNHCH2CH <SEP> (CH3) <SEP> COOC3H7
<tb> 2-(C6H4N)-H--CH2CH <SEP> (C2H )-3, <SEP> 4¯CI2C6H4CH2-2-(C5H4N) <SEP> CONHNHCH2CH <SEP> (C2H5) <SEP> COOCH <SEP> ;

  
<tb> 2-(C4H3S)-H--(CH2) <SEP> 2-C <SEP> (jHÏCH2-2-(C4H3S) <SEP> CONHNHCH2CH2COOCH3
<tb> 3- <SEP> (C4H3S)-H-- <SEP> (CH2) <SEP> 2-PCICGH4CH2-3- <SEP> (C4H3S) <SEP> CONHNHCH2CH2COOCH3
<tb> C6H5-H-- <SEP> (CH2) <SEP> 2- <SEP> PC3H7C6H4CH2-COH5CONHNHCH2CH2COOCH3
<tb> 4-CIC6H4-H--(CH2) <SEP> 2-C6H CH2-4-CICGH4CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> 3SS-CI2C6H3-H--(CH2) <SEP> 2-SZ-C4H9-3, <SEP> 5¯CI2CH3CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> 4-CH3OCaH4-H--(CH2) <SEP> 2-allyle <SEP> 4-CH3OC6H4CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> C6H6CH2-H--CH2-CGHÏCH2-C6H6CH2CONHNHCH2COOCH3
<tb> C6H6C2H4-H--CH2-X-C3H7-C6H  <SEP> (CH) <SEP> 2CONHNHCH2COOC2H5
<tb> 4-CH3C6H4-H¯-(CH2) <SEP> 2-CGH  <SEP> (CH2) <SEP> 3-4-CH3C6H4CONHNH <SEP> (CH2) <SEP> 3COOCH3
<tb> 2-CH3C6H4-H--CH2-cyclobutyle <SEP> 2-CH3C6H4CONHNHCH2COOCH3
<tb> 4-C3H7C6H4-H--CH <SEP> (CH3)

   <SEP> CH2- <SEP> cyclohexyle <SEP> 4-C3H7C6H4CONHNHCH <SEP> (CH3) <SEP> CH2COOCH3
<tb> 2, <SEP> 4-(CH3) <SEP> sC6H3-H--CH <SEP> (CH3)-pentenyle <SEP> 2, <SEP> 4-(CH3) <SEP> 2C6H3CONHNHCH <SEP> (CH3) <SEP> COOC2H5
<tb> 2-CH3-5- <SEP> (C4H20)-H--CH <SEP> (C2H5)-C6HÏ <SEP> (CH2) <SEP> 2-2-CH3-5- <SEP> (C4H20) <SEP> CONHNHCH <SEP> (C2H5) <SEP> COOCH3
<tb> 2-CH3-3-(C4H20)-H-- <SEP> (CH2) <SEP> 2-4¯CIC6H4CH2-2-CH3-3-(C4H2O) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOC2H5
<tb> 2-C3H7-5- <SEP> (C4H2S)-H--CH <SEP> (CH3)- <SEP> 4-FCGH4CH2-2-C3H7- <SEP> (C4H2S) <SEP> CONHNHCH <SEP> (CH3) <SEP> COOCH3
<tb> 2-(C4H3S) <SEP> CH2-H--CH <SEP> (CH3)-4-CH3C6H4C1 <SEP> I2-2-(C4H3S) <SEP> CH2CONHNHCH <SEP> (CH3) <SEP> COOCH3
<tb> 2-CH3-5-4C4H3O) <SEP> CH2-H--CH <SEP> (CH3)-3, <SEP> 4-Cl2C6H3CH2-2-CH3-5- <SEP> (C4H30) <SEP> CH2CONHNHCH <SEP> (CH3) <SEP> COOCH3
<tb> 2-(C4H3S) <SEP> (CH2)

   <SEP> 3-H--CH <SEP> (CH3)-254-Br2C6H3CH2-2-(C4H3S) <SEP> (CH2) <SEP> 3CONHNHCH <SEP> (CH3) <SEP> COOCH3
<tb> (COH2NS)-H--(CH2) <SEP> 2-4-IC6H4CH2- <SEP> (C3H2NS) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOC2H5
<tb> (C3H2 S)-H¯-(CH2) <SEP> 2-4¯C3H7C6H2CH2- <SEP> (C, <SEP> SH20S) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> (iso-C3H20S)-H--(CH2) <SEP> 2-C6H5CH2- <SEP> (isoC3H20S) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> (iSo-C3H2OS) <SEP> CH2-H--(CH2) <SEP> 2-C6H5CH2- <SEP> (iSOC3H2OS) <SEP> CH2CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> CH3-H-- <SEP> (CH2) <SEP> 2- <SEP> 2- <SEP> (C4H3S) <SEP> CH2- <SEP> CH3CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> C17H35-CHg--CH2-2- <SEP> (C4H3S) <SEP> (CH2) <SEP> 3-CmH35CONHNH <SEP> (CH2) <SEP> COOCH3
<tb> C17H33-H--(CH2) <SEP> 2-4-C5H4N-C17H33CONHNH <SEP> (CH2) <SEP> COOCH3
<tb> C2oH41-H-- <SEP> (CH2) <SEP> 2- <SEP> 3-GH4N-C2oH41CONHNH <SEP> (CH2)

   <SEP> COOCH3
<tb> C2H3-H-- <SEP> (CH2) <SEP> 2- <SEP> 6-CH3-2-C5H4N-C2H3CONHNH <SEP> (CH2) <SEP> COOCH3
<tb> C, <SEP> SH7-H-- <SEP> (CH2) <SEP> 2- <SEP> (C4H30) <SEP> (CH2) <SEP> 3-C3H7CONHNH <SEP> (CH2) <SEP> COOCH3
<tb> C1XH23-H--(CH2) <SEP> 2-3, <SEP> 4¯ <SEP> (CH30) <SEP> 2C6H3CH2-CI1H23CONHNH <SEP> (CH2) <SEP> COOCH3
<tb> C8Ht5-H--(CH2) <SEP> 2-4-C3H7C. <SEP> OC6H4 <SEP> (CH2) <SEP> 4-C8HJ5CONHNH <SEP> (CH2) <SEP> COOCH3
<tb>  
EMI6.1     


Ri <SEP> Tableau <SEP> 1 <SEP> (suite)
<tb> RCONHNHZCON <SEP> RCONHNEIZCOOR4
<tb> R <SEP> R, <SEP> z <SEP> R.
<tb>



  C20H39-H-¯ <SEP> (CH2) <SEP> 3-4-BrC6H4-C20H39CONHNH <SEP> (CH2) <SEP> 3COOCH3
<tb> C15H31-CH3-- <SEP> (CH2) <SEP> 2-3, <SEP> 4¯ <SEP> (C3H7O) <SEP> 2C6H3CH2-Cl5HSlCONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> C6HIl-C3H7--(CH2) <SEP> 2-6-C2H5-2-C5H3N-C6HI, <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> CH3CH <SEP> (CI)-H--(CH2) <SEP> 2-4¯C2H5C6H4CH2-CH3CH <SEP> (Cl) <SEP> CoNHNH <SEP> (CH2) <SEP> 2COOC2H5
<tb> CH2 <SEP> (NH2)-H--(CH2) <SEP> 2-n-C3H7-CH2 <SEP> (NH2) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> CH3CH <SEP> (NH2)-H-- <SEP> (CH2) <SEP> 2-C6H5CH2-CH, <SEP> 3CH <SEP> (NH2) <SEP> CONHNH <SEP> (CH2) <SEP> COOCH,,
<tb> NH2 <SEP> (CH2) <SEP> 4CH <SEP> (NH2)-H <SEP> ¯- <SEP> (CH2) <SEP> 2-C6H5CH2-NH2 <SEP> (CH2) <SEP> 4CH <SEP> (NH2) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> HOCH2CH <SEP> (NH2)-H--(CH2) <SEP> 2-n-C3H7-HOCH2CH <SEP> (NH2) <SEP> CONHNH <SEP> (CH2)

   <SEP> 2COOCH3
<tb> CH3CH <SEP> (OH) <SEP> CH <SEP> (NH2)-H-- <SEP> (CH2) <SEP> 2-C6H5CH2-CH3CH <SEP> (OH) <SEP> CH <SEP> (NHs) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCH, <SEP> j
<tb> (CH3) <SEP> 2CHCH <SEP> (NH2)-H <SEP> ¯- <SEP> (CH2) <SEP> 2-C6Hs <SEP> (CH2) <SEP> 2- <SEP> (CH3) <SEP> 2CHCH <SEP> (NH2) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOC2H5 <SEP> 
<tb> CH3 <SEP> (CH2) <SEP> 3CH <SEP> (NH2)- <SEP> H-- <SEP> (CH2) <SEP> 3- <SEP> C6H5CH2-CH3 <SEP> (CH2) <SEP> 3CH <SEP> (NH2) <SEP> CONHNH <SEP> (CH2) <SEP> 3COOCH3
<tb> C, <SEP> XH5CH2CH <SEP> (NH2)-H--(CH2) <SEP> 2-n-C, <SEP> 3H7-C6H5CH2CH <SEP> (NH2) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> 4-OHCGH4CH2CH <SEP> (NH2)-H--(CH2) <SEP> 2-C6H5CH2-4-OHCGH4CH2CH <SEP> (NH2) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> HSCH2CH <SEP> (NH2)-H-- <SEP> (CH2) <SEP> 2-n-C3H7-HSCH2CH <SEP> (NH2) <SEP> CONHNH <SEP> (CH2)

   <SEP> 2COOC2H5
<tb> H3CS <SEP> (CH2) <SEP> 2CH <SEP> (NH2)-H-- <SEP> (CH2) <SEP> 2-CGH5CH2-H3CS <SEP> (CH2) <SEP> 2CH <SEP> (NH2) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> C3H7S <SEP> (CH2) <SEP> 2CH <SEP> (NH2)-H--(CH2) <SEP> 2-CCH5CH2-C3H7S <SEP> (CH2) <SEP> 2CH <SEP> (NH2) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> CH <SEP> CH3CH <SEP> (OH) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> CI <SEP> (CH2) <SEP> -CHs-- <SEP> (CHa) <SEP> -cydopropyleCl <SEP> (CHCONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> CH3 <SEP> (CH2) <SEP> 3CH.

   <SEP> Br)-C2H5--(CH2) <SEP> 2-CGH6 <SEP> (CH2) <SEP> 4-CH3 <SEP> (CH2) <SEP> 3CH <SEP> (Br) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCHs
<tb> CH3CH <SEP> (F)-H--CH2-CGHÏCH2-CH3CH <SEP> (F) <SEP> CONHNHCH2COOC2H5
<tb> CHVCH2CH <SEP> (OCH3)-H--CH2-n-CÖH7-CH3CH2CHfOCH3) <SEP> CONHNHCH2COOC2H5
<tb> HO <SEP> (CH2) <SEP> t-H--CH <SEP> (CHg)-C, <SEP> jHgCHs-HO <SEP> (CHCONHNHCONHNHCH <SEP> (CHg) <SEP> COOC <SEP> ;

   <SEP> Hs
<tb> CoHzi-H--CH2-cyclopropyl-CH2 <SEP> CioHICONHNHCH2COOCH3
<tb> CIOHI, <SEP> 2- <SEP> (C4H, <SEP> 30) <SEP> (CH2) <SEP> 4 <SEP> CIOHIgCONHNH <SEP> (CH2) <SEP> 2COOCH
<tb> CHICOSCH2CH2-H-- <SEP> (CH2) <SEP> 4- <SEP> 2-CH3-6- <SEP> (C5H3N)- <SEP> CH,
<tb> HSCH2CH2-H--(CH2) <SEP> 2-2-CH3-5-(C4H2O) <SEP> CH2-HSCH2CH2CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> CsHgCOS <SEP> (CH) <SEP> gH--CHa-4-CNQHCHa-CHgCOS <SEP> (CHs) <SEP> gCONHNHCH2COOCaHg
<tb> cyclohexyl-CHg-H--(CH2) <SEP> 2-4-CHsCOC6H4-cyclohexyl-CH2CONHNH <SEP> (CH2) <SEP> 2COOCH.,
<tb> CeHg <SEP> (CHs) <SEP> 4-H--CH-4-CgHCOC4H4CHs-QHgHsCONHNHCHsCOOCHg
<tb> 4-CNC6H <SEP> W-H <SEP> ¯- <SEP> (CH2) <SEP> 2-4 <SEP> ¯ <SEP> G2H5COC6H4-4 <SEP> ¯ <SEP> CNCtjH4CONHNH <SEP> (CH2) <SEP> 2COOC3H7
<tb> CF3CffH4-H--(CH2) <SEP> 2-3, <SEP> 4¯Br2CfiHs-4-CFSC6H4CONHNHl <SEP> (CH2) <SEP> 2COOC3H7
<tb> CFgCsHCHa)

   <SEP> -CHg--CHa-CsHg-CFgCsHCHCONHNHCHsCOOCHg
<tb>  
EMI7.1     


Ri <SEP> Tableau <SEP> I <SEP> (suite)
<tb> RCONHNHZCON <SEP> RCONHNHZCOOR4
<tb> R2
<tb> R <SEP> R1 <SEP> Z <SEP> R2
<tb> 3, <SEP> 5-CI. <SEP> C6H3-H--(CH2) <SEP> 2-pyrryle <SEP> 3, <SEP> 5-CI2CGH3CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> 4-ICGH4-H--(CH2) <SEP> 2-pyrryl-CH2-4-IC6HCONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> 4-CH3COC6H4CH2-H--(CH2) <SEP> 2-pyrazyle <SEP> 4-CH3COC6H4CH2CONHNH <SEP> (CH2) <SEP> 2COOCHg
<tb> 4¯C3H7COC6H4-H- <SEP> (CH2) <SEP> 2-pyrazyle <SEP> 4-C3H7COC6H4CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> 3, <SEP> 5- <SEP> (CH3) <SEP> 2CGH3- <SEP> H-- <SEP> (CH2) <SEP> 2- <SEP> 3, <SEP> 5- <SEP> (CH, <SEP> 1) <SEP> 2C6H3- <SEP> 3, <SEP> 5- <SEP> (CH3) <SEP> 2C6H3CONHNH <SEP> (CH2) <SEP> 2COOC2H5
<tb> 3-Br-4-CH3C6Hs <SEP> H--(CH2) <SEP> 2-4¯C2H5C6H4-3-Br-4-CH3C6H3CONHNH <SEP> (CH2)

   <SEP> 2COOCH3
<tb> 4 <SEP> ¯ <SEP> FC6H4 <SEP> (CH2) <SEP> 4-H <SEP> ¯- <SEP> (CH2) <SEP> 2-CH3-4-FC6H4fCH2) <SEP> 4CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> 4-C, <SEP> ssH7C <SEP> ; <SEP> H4-H¯-(CH2) <SEP> 2-C5HI3-4-C,. <SEP> H7C6HICONHNH <SEP> (CH2) <SEP> 2COOClH7
<tb> cyclopropyle <SEP> H-- <SEP> (CH2) <SEP> 2- <SEP> 4-FC, <SEP> ;

   <SEP> H4CH2-cyclopropyl-CONHNH <SEP> (CH2) <SEP> zCOOC3H7
<tb> cyclobutyl- <SEP> (CH2) <SEP> H-- <SEP> (CH-CHg-cyclobutyt-CHsCONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> cyclohexyle <SEP> H--(CH2) <SEP> 2-C6H5CH2-cyclohexyl¯CH2CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> cyclopropyl- <SEP> (CH2) <SEP> 2 <SEP> H-- <SEP> (CH2) <SEP> 2-C6H5CH2-cyclopropyl- <SEP> (CH2) <SEP> 2CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> 2-(C4H2S) <SEP> (CH2) <SEP> 4-H--(CH2) <SEP> 2-CGH5CH2-2-(C4H2S) <SEP> (CH2) <SEP> 4CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> 2-C3H7- <SEP> (C4H2O)- <SEP> H-- <SEP> (CH2) <SEP> 2- <SEP> 4-CH3C6H4-2-C3H7-5- <SEP> (C4H20) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> 2- <SEP> (C4H30)- <SEP> (CH2) <SEP> 4- <SEP> H-- <SEP> (CH2) <SEP> 2- <SEP> 3-CH3C6H4-2- <SEP> (C4HgO) <SEP> (CH2) <SEP> 4CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> 2-CH3 <SEP> (C4H2S) <SEP> CH2-H <SEP> ¯- <SEP> (CH2)

   <SEP> 2-2CH3C6H4-2-CES3-5- <SEP> (C4H2S) <SEP> CH2CONHNH <SEP> (CH2) <SEP> 2COQCH <SEP> 3
<tb> CH3NHCH2-H-- <SEP> (CH2) <SEP> 2-C6H4CH2-CH3NHCH2CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> CH3 <SEP> (CH3NH) <SEP> CH- <SEP> H-- <SEP> (CH2) <SEP> 2- <SEP> CH3-CH3 <SEP> (CH3NH) <SEP> CHCONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> CH3CH2 <SEP> (C3H7NH) <SEP> CH- <SEP> H-- <SEP> (CH2) <SEP> 2- <SEP> 2- <SEP> (C5H4N)- <SEP> CH3CH2 <SEP> (C3H7NH) <SEP> CHCONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> (CH3) <SEP> 2N'CH2- <SEP> H-- <SEP> (CH2) <SEP> 2- <SEP> 3- <SEP> (C5H4N)- <SEP> (CH3) <SEP> 2NCH2CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> 4- <SEP> {C5H4N)- <SEP> H-- <SEP> (CH2) <SEP> 2- <SEP> H-4- <SEP> (GH4N) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> (CH3CO) <SEP> (CH3) <SEP> NCH2-H--(CH2) <SEP> 2-C6H5CH2- <SEP> (CH3CO) <SEP> (C <SEP> :

   <SEP> H3) <SEP> NCH2CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> 3- <SEP> (CHN)- <SEP> H-- <SEP> (CH2) <SEP> 2- <SEP> HOCH2CH2-3- <SEP> (C5H4N) <SEP> CONHNH <SEP> (CH2) <SEP> COOCH3
<tb> C6H5-H- <SEP> (CH2) <SEP> 2-CH3oCH2CH2-C6H5CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> 3 <SEP> ¯ <SEP> (C5H4N)-H-- <SEP> (CH2) <SEP> 2-H-3- <SEP> (C5H4N) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOC2H5
<tb> Br <SEP> (cH2) <SEP> 3-H--CH <SEP> (CH3)-C5H4N-Br <SEP> (CH2) <SEP> 3CONHNHCONHNHCH <SEP> (CH3) <SEP> COOCH9
<tb> CH3CHBrCHBr-H--CH2- <SEP> (C4H3O) <SEP> CH2- <SEP> CH3CH <SEP> (Br) <SEP> CH <SEP> (Br) <SEP> CONHNHCH2COOC2H 
<tb> ICH2CH2-H-- <SEP> (CH2) <SEP> 2-C4H9-ICH2CH2CONHNHCH2COOC2H 
<tb> CH3 <SEP> (CH2) <SEP> 12CH <SEP> (I)-H- <SEP> (CH2) <SEP> 2-C6H5CH2-CH3 <SEP> (CH2) <SEP> 12CH <SEP> (I) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> C3H7O <SEP> (CH2) <SEP> 4- <SEP> H-- <SEP> (CH2)

   <SEP> 2- <SEP> 4-CH3COC6H4CH-CgH7O <SEP> (CH2) <SEP> 4CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> HS <SEP> (CH2) <SEP> 4-H-CH2-allyle <SEP> HS <SEP> (CH2), <SEP> lCONHNHCH2COOC2H5
<tb> CH3S <SEP> (CH2) <SEP> 4-H-CH2-nC3H7-CH3S <SEP> (CH2) <SEP> 4CONHNHCH2CO0C2H5
<tb>    On prépare, d'une manière similaire, la -(isonicotinylhydrazino) propionyl-pipéridine.



  Dans le tableau ci-dessus, C5H4N, C4H3O, C4H3S, C3H2NO et isoC3H2NO signifient respectivement pyridyle, furyle, thiényle, thiazolyle, oxazlyle et isoxazolyle.    



   Le chlorhydrate de   N-benzyl-ss-isonicotinylhydra-    zine-propionamide (voir exemple 1) est préparé en dissolvant le composé dans une solution aqueuse contenant une proportion équivalente d'acide chlorhydrique et en évaporant la solution résultante.



   D'autres sels d'addition acides des nouveaux composés dérivés de la pyridine selon l'invention, décrits dans les exemples précédents, sont préparés en ayant recours au même mode opératoire et en utilisant l'acide sulfurique, l'acide phosphorique, l'acide bromhydrique, l'acide nitrique, l'acide benzènesulfonique et l'acide   toluènesulfonique.   




  



  Process for the preparation of therapeutic compounds
 The invention relates to the preparation of novel compounds which are valuable therapeutic agents, applicable for the treatment of mental illnesses and commonly referred to as psychotonic.



   The new compounds, the preparation of which constitutes the object of the invention, can be represented by the following general formula:
EMI1.1
 (formula 1) in which A is hydrogen or an acyl group of formula RCO-in which R is an alkyl or alkenyl radical which contains at most 20 carbon atoms and is optionally substituted by halogen or one or more amino, alkyllamino (with lower alkyl), hydroxy, lower alkoxy, mercapto, alkyl-mercapto (with lower alkyl), alkanoylamino, alkanoyl-oxy or alkanoyl-mercapto, in which the alkanoyl group contains from 2 to 4 carbon atoms;

   or a group E- (CHg) S-, where
E is a cycloalkyl residue containing from 3 to 6 carbon atoms or a pyridyl, furyl, thienyl, thiazolyl, oxazolyl, isoxazolyl group optionally substituted in the ring, and m is an integer from 0 to 4; or a group
EMI1.2
 in which X is hydrogen, a lower alkyl radical or a halogen, Y is hydrogen, a lower alkyl radical, lower alkoxy, a halogen, a trifluoromethyl, cyano or an alkanoyl radical containing from 2 to 4 atoms of carbon, and n is an integer of 0 to 4; 3 is an alkylene radical comprising a straight chain of 1 to 5 carbon atoms;

   R 1 is a hydrogen atom or a lower alkyl radical; R2 is an alkyl, alkenyl or cycloalkyl radical containing from 3 to 6 carbon atoms or a pyridyl, pyridylalkyl, furylalkyl or thienylalkl group, the alkyl radical of the latter being a lower alkyl radical, and in which groups the ring may bear a radical lower alkyl, or a group
EMI1.3
 where X, Y and n have the meaning given above.



   The invention also relates to the preparation of the acid addition salts of the basic nitrogen compounds described.



   The alkylene radicals represented by Z are derived from straight chain or branched chain aliphatic groups, and contain 1 to 5 carbon atoms in their main chain.



   The various hydrocarbon radicals described can in turn be substituted by the various substituents previously mentioned. Particularly interesting are the compounds corresponding to the formula:
EMI2.1
 where R2 is a group
EMI2.2

In addition, those compounds in which RCO is from an amino acid possess desirable therapeutic properties. The new compounds according to the invention are prepared by the reaction of an amine of formula NHRtRa with an acid of formula ANHNHZCOOH or an appropriate derivative of said acid such as a lower alkyl ester of formula ANHNHZCOOR4 in which R4 is an alkyl radical preferably containing 1 to 3 carbon atoms.

   Other acid derivatives which may be used are the acid halides and anhydrides. It goes without saying, as one skilled in the art will immediately understand, that care must be taken to minimize the side reactions which are liable to occur when using such acid derivatives, which are d: functional, due to the presence of the hydrazine moiety of the molecule.

   Although the reaction can be brought about by simply mixing the selected amine with the alkyl ester or any other derivative described above, and allowing the mixture to stand at room temperature (about 200) for a period of For times between about one and about three days, it is generally preferred to heat the reaction mixture to a temperature of between about 60 and about 2000, since this procedure allows the reaction time to be considerably shortened. Thus, for example, it can be seen that an excellent yield of product is obtained when the reaction is carried out at about 1300 for a time of between 2 and 4 hours.



  The reagents are generally used in equal molar concentrations, although the process according to the invention is advantageously carried out with a slight molar excess (up to 10%) of amine. Using a large excess does not lead to any appreciable benefit and is not beneficial. After the reaction is complete, the cooled reaction mass is recrystallized from a suitable solvent, such as ethyl acetate, lower alkanols such as methanol, ethanol, propanol, etc., and the like.



   The new therapeutic agents prepared according to the invention have an activity, in the treatment of mental depression, considerably greater than that of the agents known in the prior art. In addition, the new agents have a higher therapeutic index than the previously known agents. The therapeutic index means, as used in the present description, the ratio of therapeutic activity to toxicity.



  The use for the treatment of mental depression of many agents known in the prior art is accompanied in the patient by considerable toxic reactions. The ratio of activity to toxicity of a therapeutic agent is obviously of the utmost importance in the selection of such an agent. Although many agents are endowed with quite remarkable therapeutic activity, their use is considerably hampered due to excessive toxicity. These therapeutic agents, because of their very high therapeutic index, are more interesting than the agents previously known for the treatment of mental depression.

   These new therapeutic agents, in which R is a pyridine radical, furthermore possess appreciable anti-tuberculosis activity, while those in which R is a benzene, thiophene or furan radical, do not possess the latter activity.



   The doctor will prescribe the daily doses of these therapeutic agents to be used. The dosage will depend on the degree of mental depression, whether it is mild or severe. If it is mild, a dose of 10 to 50 mg per day can be prescribed. For severe depression, considerably higher daily doses may be needed and it is, for example, possible to prescribe up to 150 mg or even more. Tablets or capsules of 10, 25, 50 and 150 mg of the new therapeutic agents are suitable modes of presentation for daily administration.

   Such tablets or capsules can be prepared from mixtures of these compounds with well known pharmaceutical excipients such as starch, sugar, tapioca, certain forms of clay and the like. Alternatively, it is possible to make liquid preparations from mixtures of these therapeutic agents and pharmaceutically acceptable liquid media such as water, aqueous glycols, sugar solutions and the like which may contain conventional flavoring and coloring agents.



   Since a large number of these compounds are basic, it is possible to take advantage of the solubility in water of the salts which these compounds form with acids, to carry out the isolation and / or the purification of the aforesaid. compounds and for the preparation of aqueous solutions of these new compounds for their oral or parenteral administration. It goes without saying that only salts formed from pharmaceutically acceptable acids can be used for therapeutic applications. Particularly effective salts are those formed with pharmaceutically acceptable acids having a pK value of less than or at most equal to 3. Such acids are well known in the art.

   These are, for example, hydrochloric, hydrobromic, nitric, phosphoric, benzenesulfonic, toluenesulfonic, methylsulfonic, ethylsulfonic and the like. These salts can be prepared by the procedures usually used in the art and consisting, for example, in reacting the compound with one equivalent of the acid chosen in aqueous solution, then in concentrating the solution. It is also possible to use other known procedures.



      Exerraple 1
 N-henzyl- propionamide
 A suspension of 7.5 g (0.034 mole) of 1-isonicotinyl-2- (carbomethoxyethyl) hydrazine and 5 ml of benzylamine is heated while stirring at 1300 for 3 hours. The cooled mass is then recrystallized from ethyl acetate to give white needles melting at 151.1-152.1. Elemental analysis gives the following results:
 Calculated for C10H18N4O:
   C = 64.43; H = 6.07; N = 18.77
 Found: C = 64.43; H = 6.27: N = 19.17.



   Example 2
 N-benzyl-ss- (benzoylhydrazino) propionamide
 This compound is prepared by the procedure of Example 1 using 1-benzoyl-2- (carboethoxyethyl) hydrazine in place of the corresponding isonicotinyl compound. The product melts at 164-165.



  Elemental analysis is in good agreement with the calculated values.



   Example 3 N- (p-chlorobenzyl) - (ss-isonicotinylhydrazino) -
 propionamide
 The procedure of Example 1 is repeated using p-chlorobenzylamine in place of benzylamine. The product melts at 162-163.



   Example 4 N- (4-picolyl) -ss- (benzoylhydrazine) propionamide
 This compound is prepared by the procedure of Example 1 using 4-picolylamine and 1-benzoyl-2- (carbomethoxyethyl) hydrazine. The product melts at 125-127. Other N-substituted p- (acylhydrazino) propionamides, prepared using suitable 1-acyl-2- (carboalkoxyethyl) hydrazines and suitable amens are: N-benzyl-p- (2-furoylhydrazine) propionamide
 (P. F. 183-184) N-furfuryl-p- (isonicotinylhydrazine) propionamide
 (P. F. 129-1310) N-phenylethyl-p- (isonicotinylhydrazine) propionamide
 (P.

   F. 145-147)
N- (3,4-dimethoxyphenylethyl) -ss- (isonicotinylhydra
 zine) propionamide (P. F. 110-114) N- (3-methylbenzyl-p- (isonicotinylhydrazine) propion
 amide (. P. F. 114-116)
N- (4-methylbenzyl) -p-isonicotinylhydrazine) propion-
 amide (P. F. 133-1350) N- (2-chlorobenzyl) -p- (isonicotinylhydrazine) propion
 amide (P. F. 148-1490) N- (2-methylbenzyl) -ss- (isonicotinylhydrazine) propion
 amide (P. F. 148-149)
N- (3,4-dichlorobenzyl) -ss- (isonicotinylhydrazine) pro
 pionamide (P. F. 139-140) N- (2, 4-dichlorobenzyl) -p- (isonicotinylhydrazine) pro
 pionamide (P.

   F. 137-139o)
N-benzyl-ss- (nictinylhydraizne) propionamide
 (P. F. 125-1260) N-benzyl-p- (cyclohexylcarbohydrazine) propionamide
 (P. F. 150-1520) N-methyl-p- (isonicotinylhydrazine) propionamide
 (P. F. 119) N-ethyl-ss- (isonicotinylhydrazine) propionamide
 (P. F. 131-132)
N-n-propyl-ss- (isonictinylhydrazine) propionamide
 (P. F. 118-120) N-i-propyl-p- (isonicotinylhydrazine) propionamide
 (P. F. 163-165) N-n-butyl-p- (isonicotinylhydrazine) propionamide
 (P. F. 120-122) N-i-butyl-p- (isonicotinylhydrazine) propionamide
 (P.

   F. 146-147)
N-cyclohexyl-p- (isonicotinylhydrazine) propionamide
 (P. F. 166-167) N-allyl-ss- (isonicotinylhydrazine) propionamide
 (P. F. 117-119) N-phenethyl-p- (isonicotinylhydrazine) propionamide
 (P. F. 145-147)
N-benzyl-p- (3-chlorobenzoylhydrazine) propionamide
 (P. F. 151-153)
N-benzyl-ss- (4-fluorobenzoylhydrazine) propionamide
 (P. F. 214-216)
 Example 5 N-benzyl-a-hydrazinoacetamide
 This compound is prepared by the procedure of Example 1 using benzylamine and methyl α-hydrazine-acetate.



   Likewise, other N-substituted hydrazinekanoamides are prepared in a similar manner using suitable amines. We thus obtain: N-methyl-N-benzyl-a-hydrazineacetamide
N-pyridyl-a.-hydrazineacetamide
N-n-propyl- &alpha; -hydrazineacetamide
N- (p-chlorbenzyl) -a-hydrazineacetamide
N- (2-furfuryl) -a-hydrazineacetamide
N- (allyl) -a-hydrazineacetamide
N-benzyl-p-hydrazinepropionamide
N-allyl-p-hydrazinepropionamide
N-n-propyl-e-hydrazinehexaneamide
N-cyclobutyl- &alpha; -hydrazineacetamide
N-pentenyl-a-hydrazinepropionamide
N-cyclohexyl-N-methyl-p-hydrazinebutyramide
N-phenethyl- &alpha;

  -hydrazineacetamide
N-4-chlorobenzyl-p-hydrazinepropionamide
N-4-fluorobenzyl-a-hydrazinepropionamide
N-4-methylbenzyl-a-hydrazinepropionamide
N-3, 4-dichlorobenzyl-a-hydrazinepropionamide
N-2, 4-dibromobenzyl-a-hydrazinepropionamide
N-4-iodobenzyl-p-hydrazinepropionamide
N-3-methylbenzyl-p-hydrazinepropionamide
N-4-propylphenyl-p-hydrazinepropionamide
N-phenyl-p-hydrazinepropionamide
N-furfuryl-p-hydrazinepropionamide
N-thienylmethyl-p-hydrazinepropionamide
N-2-methylfurfuryl-ss-hydrzinepropionamide
N-2-pyridyl-p-hydrazinepropionamide
N-3-pyridyl-p-hydrazmepropionamide
N-2-pyridylpropyl-p-hydrazinepropionamide
N-2-furfurylpropyl-p-hydrazinepropionamide
N- (3, 4-dimethoxybenzyl) -p-hydrazinepropionamide
N- (4-trifluoromethylbenzyl)

  -ss-hydrazinpropion
 amide
N- (3-acetylphenyl) -p-hydrazinepropionamide
N- (4-Butyrylphenylbutyl) -p-hydrazinepropionamide
N- (4-bromophenyl) - # - hydrazinebutyramide
N- (3,4-dipropoxybenzyl) -ss-hydrazineptropionamide
N- (4-methoxyphenyl) -p-hydrazinepropionamide
N- (6-ethyl-2-pyridyl) -p-hydrazinepropionamide
N- (4-ethylbenzyl) -ss-hydrazinepropionamide
 Example 6
 A number of N-substituted acylhydrazine alkanolamines are prepared using the procedure of Example 1 and starting with the appropriate acyl-2- (carboalkoxyalkyl) hydrazines and appropriate amines.



   Table I gives the list of such compounds with the corresponding substituted hydrazines from which they are obtained with R1R2NH.
EMI4.1





  Ri <SEP> Tableati <SEP> I
<tb> RCONHNHZCON <SEP> RCONHNHZCOOR4
<tb> R2
<tb> R <SEP> R <SEP>; <SEP> z <SEP> RS
<tb> C, <SEP>; <SEP> HÏ-H <SEP> ¯- <SEP> (CH) <SEP> 2-pBrC, <SEP> jH4CH2-C <H6CONHNHCH2CH2COOCH <SEP> s
<tb> 2- <SEP> (CsH4N) -CH <SEP> 3 - CH <SEP> (CH3) <SEP> cH2-pIC, <SEP> jH <SEP> CHw-2- <SEP> (CÏH, <SEP>; <SEP> N) <SEP> CONHNHCH <SEP> (CH3) <SEP> CH2COOCH <SEP>: <SEP> j
<tb> 3- <SEP> (CsH. <SEP> N) -H-- <SEP> (CHs), - pFCt. <SEP> H. <SEP> jCHa- <SEP> 3- <SEP> (C5HN) <SEP> CONHNH <SEP> (CH2) <SEP> ÏCOOc2H
<tb> QH, -CH, - CH <SEP> (CH,) <SEP> CHa-6-CH <SEP> (CsHgN) <SEP> CH2- <SEP> QH5CONHNHCH <SEP> (QHg) <SEP> CHaCOOCgH,
<tb> 4- {C6HIN) -H - (cH2) <SEP>; -pC2HÏOCtiH4CH2-4- (CÏH4N) <SEP> CONHNH <SEP> (CH2) <SEP> 3COOC3H7
<tb> CjH <SEP> CH, <SEP>; - CH <SEP> (CH3) <SEP> CH <SEP> (CH <SEP>:

   <SEP>;) - pCHsOCeH. <SEP> tCHa- <SEP> CH5CONHNHCH <SEP> (CH) <SEP> CH <SEP> (CH3) <SEP> COOCH <SEP>; <SEP>;
<tb> 4- (C5H4N) -CH. <SEP>; - CH <SEP> (CH3) <SEP> CH <SEP> (C2Hg) -pC3H70CrjH <SEP> CH2¯ <SEP> 4- (CsH4N) <SEP> CONHNHCH <SEP> (CH3) <SEP > CH <SEP> (CoH3) <SEP> C, <SEP> OOCoH, <SEP>;
<tb> CfjH3-C <SEP> H7 - CH <SEP> (C, <SEP> 3H7) <SEP> CHw-CaH3CaH4-CfiH3CoNHNHCH <SEP> (C3H7) <SEP> CH2COOC2HÏ
<tb> 4- <SEP> (CgHN) -H-- <SEP> (CHa) <SEP> -C, <SEP> jHgC- <SEP> 4- <SEP> (CgH) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> 2- <SEP> (CO) -H-- <SEP> (CHa) <SEP> a-2- <SEP> (CgH. <SEP> tN) <SEP> CHg- <SEP> 2- < SEP> (CO) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCH <SEP>;

  
<tb> 4- <SEP> (c6H4N) -H-- <SEP> (CHW,), - 2- (C6HlN) <SEP> C, <SEP> H, -4- (CÏH4N) <SEP> CONHNHCH2CH2COOCBHÏ
<tb> 3- <SEP> (C4H30) -CH <SEP> 3 - CH2CH <SEP> (CH3) - <SEP> (c4Ht3o) <SEP> cH2-3- <SEP> (C4H30) <SEP> CONHNHCH2CH <SEP> (CH3) <SEP> COOCH, <SEP>;
<tb>
EMI5.1


Rl <SEP> Tableall <SEP> I <SEP> (continued)
<tb> RCONHNHZCON <SEP> RCONHNHZCOOR4
<tb> R
<tb> R2
<tb> R <SEP> R, <SEP> z <SEP> R2
<tb> R <SEP> RI <SEP> Z <SEP> R2
<tb> CGH6-H - CH2CH <SEP> (CH3) - <SEP> (C4H3O) <SEP> C2H4-C6H6CONHNHCH2CH <SEP> (CH3) <SEP> COOC3H7
<tb> 2- (C6H4N) -H - CH2CH <SEP> (C2H) -3, <SEP> 4¯CI2C6H4CH2-2- (C5H4N) <SEP> CONHNHCH2CH <SEP> (C2H5) <SEP> COOCH <SEP >;

  
<tb> 2- (C4H3S) -H - (CH2) <SEP> 2-C <SEP> (jHÏCH2-2- (C4H3S) <SEP> CONHNHCH2CH2COOCH3
<tb> 3- <SEP> (C4H3S) -H-- <SEP> (CH2) <SEP> 2-PCICGH4CH2-3- <SEP> (C4H3S) <SEP> CONHNHCH2CH2COOCH3
<tb> C6H5-H-- <SEP> (CH2) <SEP> 2- <SEP> PC3H7C6H4CH2-COH5CONHNHCH2CH2COOCH3
<tb> 4-CIC6H4-H - (CH2) <SEP> 2-C6H CH2-4-CICGH4CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> 3SS-CI2C6H3-H - (CH2) <SEP> 2-SZ-C4H9-3, <SEP> 5¯CI2CH3CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> 4-CH3OCaH4-H - (CH2) <SEP> 2-allyl <SEP> 4-CH3OC6H4CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> C6H6CH2-H - CH2-CGHÏCH2-C6H6CH2CONHNHCH2COOCH3
<tb> C6H6C2H4-H - CH2-X-C3H7-C6H <SEP> (CH) <SEP> 2CONHNHCH2COOC2H5
<tb> 4-CH3C6H4-H¯- (CH2) <SEP> 2-CGH <SEP> (CH2) <SEP> 3-4-CH3C6H4CONHNH <SEP> (CH2) <SEP> 3COOCH3
<tb> 2-CH3C6H4-H - CH2-cyclobutyl <SEP> 2-CH3C6H4CONHNHCH2COOCH3
<tb> 4-C3H7C6H4-H - CH <SEP> (CH3)

   <SEP> CH2- <SEP> cyclohexyle <SEP> 4-C3H7C6H4CONHNHCH <SEP> (CH3) <SEP> CH2COOCH3
<tb> 2, <SEP> 4- (CH3) <SEP> sC6H3-H - CH <SEP> (CH3) -pentenyle <SEP> 2, <SEP> 4- (CH3) <SEP> 2C6H3CONHNHCH <SEP> (CH3) <SEP> COOC2H5
<tb> 2-CH3-5- <SEP> (C4H20) -H - CH <SEP> (C2H5) -C6HÏ <SEP> (CH2) <SEP> 2-2-CH3-5- <SEP> (C4H20 ) <SEP> CONHNHCH <SEP> (C2H5) <SEP> COOCH3
<tb> 2-CH3-3- (C4H20) -H-- <SEP> (CH2) <SEP> 2-4¯CIC6H4CH2-2-CH3-3- (C4H2O) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOC2H5
<tb> 2-C3H7-5- <SEP> (C4H2S) -H - CH <SEP> (CH3) - <SEP> 4-FCGH4CH2-2-C3H7- <SEP> (C4H2S) <SEP> CONHNHCH <SEP > (CH3) <SEP> COOCH3
<tb> 2- (C4H3S) <SEP> CH2-H - CH <SEP> (CH3) -4-CH3C6H4C1 <SEP> I2-2- (C4H3S) <SEP> CH2CONHNHCH <SEP> (CH3) <SEP> COOCH3
<tb> 2-CH3-5-4C4H3O) <SEP> CH2-H - CH <SEP> (CH3) -3, <SEP> 4-Cl2C6H3CH2-2-CH3-5- <SEP> (C4H30) <SEP > CH2CONHNHCH <SEP> (CH3) <SEP> COOCH3
<tb> 2- (C4H3S) <SEP> (CH2)

   <SEP> 3-H - CH <SEP> (CH3) -254-Br2C6H3CH2-2- (C4H3S) <SEP> (CH2) <SEP> 3CONHNHCH <SEP> (CH3) <SEP> COOCH3
<tb> (COH2NS) -H - (CH2) <SEP> 2-4-IC6H4CH2- <SEP> (C3H2NS) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOC2H5
<tb> (C3H2 S) -H¯- (CH2) <SEP> 2-4¯C3H7C6H2CH2- <SEP> (C, <SEP> SH20S) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> (iso-C3H20S) -H - (CH2) <SEP> 2-C6H5CH2- <SEP> (isoC3H20S) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> (iSo-C3H2OS) <SEP> CH2-H - (CH2) <SEP> 2-C6H5CH2- <SEP> (iSOC3H2OS) <SEP> CH2CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> CH3-H-- <SEP> (CH2) <SEP> 2- <SEP> 2- <SEP> (C4H3S) <SEP> CH2- <SEP> CH3CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> C17H35-CHg - CH2-2- <SEP> (C4H3S) <SEP> (CH2) <SEP> 3-CmH35CONHNH <SEP> (CH2) <SEP> COOCH3
<tb> C17H33-H - (CH2) <SEP> 2-4-C5H4N-C17H33CONHNH <SEP> (CH2) <SEP> COOCH3
<tb> C2oH41-H-- <SEP> (CH2) <SEP> 2- <SEP> 3-GH4N-C2oH41CONHNH <SEP> (CH2)

   <SEP> COOCH3
<tb> C2H3-H-- <SEP> (CH2) <SEP> 2- <SEP> 6-CH3-2-C5H4N-C2H3CONHNH <SEP> (CH2) <SEP> COOCH3
<tb> C, <SEP> SH7-H-- <SEP> (CH2) <SEP> 2- <SEP> (C4H30) <SEP> (CH2) <SEP> 3-C3H7CONHNH <SEP> (CH2) <SEP > COOCH3
<tb> C1XH23-H - (CH2) <SEP> 2-3, <SEP> 4¯ <SEP> (CH30) <SEP> 2C6H3CH2-CI1H23CONHNH <SEP> (CH2) <SEP> COOCH3
<tb> C8Ht5-H - (CH2) <SEP> 2-4-C3H7C. <SEP> OC6H4 <SEP> (CH2) <SEP> 4-C8HJ5CONHNH <SEP> (CH2) <SEP> COOCH3
<tb>
EMI6.1


Ri <SEP> Table <SEP> 1 <SEP> (continued)
<tb> RCONHNHZCON <SEP> RCONHNEIZCOOR4
<tb> R <SEP> R, <SEP> z <SEP> R.
<tb>



  C20H39-H-¯ <SEP> (CH2) <SEP> 3-4-BrC6H4-C20H39CONHNH <SEP> (CH2) <SEP> 3COOCH3
<tb> C15H31-CH3-- <SEP> (CH2) <SEP> 2-3, <SEP> 4¯ <SEP> (C3H7O) <SEP> 2C6H3CH2-Cl5HSlCONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> C6HIl-C3H7 - (CH2) <SEP> 2-6-C2H5-2-C5H3N-C6HI, <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> CH3CH <SEP> (CI) -H - (CH2) <SEP> 2-4¯C2H5C6H4CH2-CH3CH <SEP> (Cl) <SEP> CoNHNH <SEP> (CH2) <SEP> 2COOC2H5
<tb> CH2 <SEP> (NH2) -H - (CH2) <SEP> 2-n-C3H7-CH2 <SEP> (NH2) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> CH3CH <SEP> (NH2) -H-- <SEP> (CH2) <SEP> 2-C6H5CH2-CH, <SEP> 3CH <SEP> (NH2) <SEP> CONHNH <SEP> (CH2) < SEP> COOCH ,,
<tb> NH2 <SEP> (CH2) <SEP> 4CH <SEP> (NH2) -H <SEP> ¯- <SEP> (CH2) <SEP> 2-C6H5CH2-NH2 <SEP> (CH2) <SEP> 4CH <SEP> (NH2) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> HOCH2CH <SEP> (NH2) -H - (CH2) <SEP> 2-n-C3H7-HOCH2CH <SEP> (NH2) <SEP> CONHNH <SEP> (CH2)

   <SEP> 2COOCH3
<tb> CH3CH <SEP> (OH) <SEP> CH <SEP> (NH2) -H-- <SEP> (CH2) <SEP> 2-C6H5CH2-CH3CH <SEP> (OH) <SEP> CH <SEP > (NHs) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCH, <SEP> j
<tb> (CH3) <SEP> 2CHCH <SEP> (NH2) -H <SEP> ¯- <SEP> (CH2) <SEP> 2-C6Hs <SEP> (CH2) <SEP> 2- <SEP> ( CH3) <SEP> 2CHCH <SEP> (NH2) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOC2H5 <SEP>
<tb> CH3 <SEP> (CH2) <SEP> 3CH <SEP> (NH2) - <SEP> H-- <SEP> (CH2) <SEP> 3- <SEP> C6H5CH2-CH3 <SEP> (CH2) <SEP> 3CH <SEP> (NH2) <SEP> CONHNH <SEP> (CH2) <SEP> 3COOCH3
<tb> C, <SEP> XH5CH2CH <SEP> (NH2) -H - (CH2) <SEP> 2-nC, <SEP> 3H7-C6H5CH2CH <SEP> (NH2) <SEP> CONHNH <SEP> (CH2 ) <SEP> 2COOCH3
<tb> 4-OHCGH4CH2CH <SEP> (NH2) -H - (CH2) <SEP> 2-C6H5CH2-4-OHCGH4CH2CH <SEP> (NH2) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> HSCH2CH <SEP> (NH2) -H-- <SEP> (CH2) <SEP> 2-n-C3H7-HSCH2CH <SEP> (NH2) <SEP> CONHNH <SEP> (CH2)

   <SEP> 2COOC2H5
<tb> H3CS <SEP> (CH2) <SEP> 2CH <SEP> (NH2) -H-- <SEP> (CH2) <SEP> 2-CGH5CH2-H3CS <SEP> (CH2) <SEP> 2CH <SEP > (NH2) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> C3H7S <SEP> (CH2) <SEP> 2CH <SEP> (NH2) -H - (CH2) <SEP> 2-CCH5CH2-C3H7S <SEP> (CH2) <SEP> 2CH <SEP> (NH2 ) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> CH <SEP> CH3CH <SEP> (OH) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> CI <SEP> (CH2) <SEP> -CHs-- <SEP> (CHa) <SEP> -cydopropyleCl <SEP> (CHCONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> CH3 <SEP> (CH2) <SEP> 3CH.

   <SEP> Br) -C2H5 - (CH2) <SEP> 2-CGH6 <SEP> (CH2) <SEP> 4-CH3 <SEP> (CH2) <SEP> 3CH <SEP> (Br) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCHs
<tb> CH3CH <SEP> (F) -H - CH2-CGHÏCH2-CH3CH <SEP> (F) <SEP> CONHNHCH2COOC2H5
<tb> CHVCH2CH <SEP> (OCH3) -H - CH2-n-CÖH7-CH3CH2CHfOCH3) <SEP> CONHNHCH2COOC2H5
<tb> HO <SEP> (CH2) <SEP> tH - CH <SEP> (CHg) -C, <SEP> jHgCHs-HO <SEP> (CHCONHNHCONHNHCH <SEP> (CHg) <SEP> COOC <SEP> ;

   <SEP> Hs
<tb> CoHzi-H - CH2-cyclopropyl-CH2 <SEP> CioHICONHNHCH2COOCH3
<tb> CIOHI, <SEP> 2- <SEP> (C4H, <SEP> 30) <SEP> (CH2) <SEP> 4 <SEP> CIOHIgCONHNH <SEP> (CH2) <SEP> 2COOCH
<tb> CHICOSCH2CH2-H-- <SEP> (CH2) <SEP> 4- <SEP> 2-CH3-6- <SEP> (C5H3N) - <SEP> CH,
<tb> HSCH2CH2-H - (CH2) <SEP> 2-2-CH3-5- (C4H2O) <SEP> CH2-HSCH2CH2CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> CsHgCOS <SEP> (CH) <SEP> gH - CHa-4-CNQHCHa-CHgCOS <SEP> (CHs) <SEP> gCONHNHCH2COOCaHg
<tb> cyclohexyl-CHg-H - (CH2) <SEP> 2-4-CHsCOC6H4-cyclohexyl-CH2CONHNH <SEP> (CH2) <SEP> 2COOCH.,
<tb> CeHg <SEP> (CHs) <SEP> 4-H - CH-4-CgHCOC4H4CHs-QHgHsCONHNHCHsCOOCHg
<tb> 4-CNC6H <SEP> WH <SEP> ¯- <SEP> (CH2) <SEP> 2-4 <SEP> ¯ <SEP> G2H5COC6H4-4 <SEP> ¯ <SEP> CNCtjH4CONHNH <SEP> (CH2 ) <SEP> 2COOC3H7
<tb> CF3CffH4-H - (CH2) <SEP> 2-3, <SEP> 4¯Br2CfiHs-4-CFSC6H4CONHNHl <SEP> (CH2) <SEP> 2COOC3H7
<tb> CFgCsHCHa)

   <SEP> -CHg - CHa-CsHg-CFgCsHCHCONHNHCHsCOOCHg
<tb>
EMI7.1


Ri <SEP> Table <SEP> I <SEP> (continued)
<tb> RCONHNHZCON <SEP> RCONHNHZCOOR4
<tb> R2
<tb> R <SEP> R1 <SEP> Z <SEP> R2
<tb> 3, <SEP> 5-CI. <SEP> C6H3-H - (CH2) <SEP> 2-pyrryl <SEP> 3, <SEP> 5-CI2CGH3CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> 4-ICGH4-H - (CH2) <SEP> 2-pyrryl-CH2-4-IC6HCONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> 4-CH3COC6H4CH2-H - (CH2) <SEP> 2-pyrazyle <SEP> 4-CH3COC6H4CH2CONHNH <SEP> (CH2) <SEP> 2COOCHg
<tb> 4¯C3H7COC6H4-H- <SEP> (CH2) <SEP> 2-pyrazyle <SEP> 4-C3H7COC6H4CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> 3, <SEP> 5- <SEP> (CH3) <SEP> 2CGH3- <SEP> H-- <SEP> (CH2) <SEP> 2- <SEP> 3, <SEP> 5- <SEP > (CH, <SEP> 1) <SEP> 2C6H3- <SEP> 3, <SEP> 5- <SEP> (CH3) <SEP> 2C6H3CONHNH <SEP> (CH2) <SEP> 2COOC2H5
<tb> 3-Br-4-CH3C6Hs <SEP> H - (CH2) <SEP> 2-4¯C2H5C6H4-3-Br-4-CH3C6H3CONHNH <SEP> (CH2)

   <SEP> 2COOCH3
<tb> 4 <SEP> ¯ <SEP> FC6H4 <SEP> (CH2) <SEP> 4-H <SEP> ¯- <SEP> (CH2) <SEP> 2-CH3-4-FC6H4fCH2) <SEP> 4CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> 4-C, <SEP> ssH7C <SEP>; <SEP> H4-H¯- (CH2) <SEP> 2-C5HI3-4-C ,. <SEP> H7C6HICONHNH <SEP> (CH2) <SEP> 2COOClH7
<tb> cyclopropyle <SEP> H-- <SEP> (CH2) <SEP> 2- <SEP> 4-FC, <SEP>;

   <SEP> H4CH2-cyclopropyl-CONHNH <SEP> (CH2) <SEP> zCOOC3H7
<tb> cyclobutyl- <SEP> (CH2) <SEP> H-- <SEP> (CH-CHg-cyclobutyt-CHsCONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> cyclohexyl <SEP> H - (CH2) <SEP> 2-C6H5CH2-cyclohexyl¯CH2CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> cyclopropyl- <SEP> (CH2) <SEP> 2 <SEP> H-- <SEP> (CH2) <SEP> 2-C6H5CH2-cyclopropyl- <SEP> (CH2) <SEP> 2CONHNH <SEP> ( CH2) <SEP> 2COOCH3
<tb> 2- (C4H2S) <SEP> (CH2) <SEP> 4-H - (CH2) <SEP> 2-CGH5CH2-2- (C4H2S) <SEP> (CH2) <SEP> 4CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> 2-C3H7- <SEP> (C4H2O) - <SEP> H-- <SEP> (CH2) <SEP> 2- <SEP> 4-CH3C6H4-2-C3H7-5- <SEP> (C4H20) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> 2- <SEP> (C4H30) - <SEP> (CH2) <SEP> 4- <SEP> H-- <SEP> (CH2) <SEP> 2- <SEP> 3-CH3C6H4-2- < SEP> (C4HgO) <SEP> (CH2) <SEP> 4CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> 2-CH3 <SEP> (C4H2S) <SEP> CH2-H <SEP> ¯- <SEP> (CH2)

   <SEP> 2-2CH3C6H4-2-CES3-5- <SEP> (C4H2S) <SEP> CH2CONHNH <SEP> (CH2) <SEP> 2COQCH <SEP> 3
<tb> CH3NHCH2-H-- <SEP> (CH2) <SEP> 2-C6H4CH2-CH3NHCH2CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> CH3 <SEP> (CH3NH) <SEP> CH- <SEP> H-- <SEP> (CH2) <SEP> 2- <SEP> CH3-CH3 <SEP> (CH3NH) <SEP> CHCONHNH <SEP > (CH2) <SEP> 2COOCH3
<tb> CH3CH2 <SEP> (C3H7NH) <SEP> CH- <SEP> H-- <SEP> (CH2) <SEP> 2- <SEP> 2- <SEP> (C5H4N) - <SEP> CH3CH2 <SEP > (C3H7NH) <SEP> CHCONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> (CH3) <SEP> 2N'CH2- <SEP> H-- <SEP> (CH2) <SEP> 2- <SEP> 3- <SEP> (C5H4N) - <SEP> (CH3) <SEP > 2NCH2CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> 4- <SEP> {C5H4N) - <SEP> H-- <SEP> (CH2) <SEP> 2- <SEP> H-4- <SEP> (GH4N) <SEP> CONHNH <SEP> ( CH2) <SEP> 2COOCH3
<tb> (CH3CO) <SEP> (CH3) <SEP> NCH2-H - (CH2) <SEP> 2-C6H5CH2- <SEP> (CH3CO) <SEP> (C <SEP>:

   <SEP> H3) <SEP> NCH2CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> 3- <SEP> (CHN) - <SEP> H-- <SEP> (CH2) <SEP> 2- <SEP> HOCH2CH2-3- <SEP> (C5H4N) <SEP> CONHNH <SEP> ( CH2) <SEP> COOCH3
<tb> C6H5-H- <SEP> (CH2) <SEP> 2-CH3oCH2CH2-C6H5CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> 3 <SEP> ¯ <SEP> (C5H4N) -H-- <SEP> (CH2) <SEP> 2-H-3- <SEP> (C5H4N) <SEP> CONHNH <SEP> (CH2) < SEP> 2COOC2H5
<tb> Br <SEP> (cH2) <SEP> 3-H - CH <SEP> (CH3) -C5H4N-Br <SEP> (CH2) <SEP> 3CONHNHCONHNHCH <SEP> (CH3) <SEP> COOCH9
<tb> CH3CHBrCHBr-H - CH2- <SEP> (C4H3O) <SEP> CH2- <SEP> CH3CH <SEP> (Br) <SEP> CH <SEP> (Br) <SEP> CONHNHCH2COOC2H
<tb> ICH2CH2-H-- <SEP> (CH2) <SEP> 2-C4H9-ICH2CH2CONHNHCH2COOC2H
<tb> CH3 <SEP> (CH2) <SEP> 12CH <SEP> (I) -H- <SEP> (CH2) <SEP> 2-C6H5CH2-CH3 <SEP> (CH2) <SEP> 12CH <SEP> (I) <SEP> CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> C3H7O <SEP> (CH2) <SEP> 4- <SEP> H-- <SEP> (CH2)

   <SEP> 2- <SEP> 4-CH3COC6H4CH-CgH7O <SEP> (CH2) <SEP> 4CONHNH <SEP> (CH2) <SEP> 2COOCH3
<tb> HS <SEP> (CH2) <SEP> 4-H-CH2-allyl <SEP> HS <SEP> (CH2), <SEP> lCONHNHCH2COOC2H5
<tb> CH3S <SEP> (CH2) <SEP> 4-H-CH2-nC3H7-CH3S <SEP> (CH2) <SEP> 4CONHNHCH2CO0C2H5
<tb> - (isonicotinylhydrazino) propionyl-piperidine is prepared in a similar manner.



  In the table above, C5H4N, C4H3O, C4H3S, C3H2NO and isoC3H2NO mean pyridyl, furyl, thienyl, thiazolyl, oxazlyl and isoxazolyl, respectively.



   N-Benzyl-ss-isonicotinylhydrazine-propionamide hydrochloride (see Example 1) is prepared by dissolving the compound in an aqueous solution containing an equivalent proportion of hydrochloric acid and evaporating the resulting solution.



   Other acid addition salts of the novel compounds derived from pyridine according to the invention, described in the preceding examples, are prepared using the same procedure and using sulfuric acid, phosphoric acid, hydrobromic acid, nitric acid, benzenesulfonic acid and toluenesulfonic acid.

Claims (1)

REVENDICATION Procédé de préparation d'un composé de formule EMI8.1 dans laquelle A est de l'hydrogène ou un groupe acyle de formule RCO-dans laquelle R est un radical alcoyle ou alcényle qui contient au plus 20 atomes de carbone et est éventuellement substitué par de l'ha- logène ou un ou des restes amino, alcoylamino (avec alcoyle inférieur), hydroxy, alcoxy inférieur, mercapto, alcoylmercapto (avec alcoyle inférieur), alca- noyl-amino-, alcanoyloxy ou alcanoylmercapto, dans lesquels le groupe alcanoyle contient de 2 à 4 atomes de carbone ; CLAIM Process for the preparation of a compound of the formula EMI8.1 in which A is hydrogen or an acyl group of the formula RCO- in which R is an alkyl or alkenyl radical which contains at most 20 carbon atoms and is optionally substituted by halogen or amino residue (s) , alkyllamino (with lower alkyl), hydroxy, lower alkoxy, mercapto, alkylmercapto (with lower alkyl), alkanoyl-amino-, alkanoyloxy or alkanoylmercapto, in which the alkanoyl group contains from 2 to 4 carbon atoms; ou un groupe E-(CH2) m-, ou E est un reste cycloalcoyle contenant de 3 à 6 atomes de carbone ou un groupe pyridyle, furyle, thiényle, thiazolyle, oxazolyle, isoxazolyle éventuellement substitués dans le noyau, et m est un nombre entier de 0 à 4 ; ou un groupe EMI8.2 dans lequel X est de l'hydrogène, un radical alcoyle inférieur ou un halogène ; Y est de l'hydrogène, un radical alcoyle inférieur, alcoxy inférieur, un halogène, un radical trifluorométhyle, cyano ou un alcanoyle contenant de 2 à 4 atomes de carbone, et n est un nombre entier de 0 à 4, Z est un radical alcoylène comprenant une chaîne droite de 1 à 5 atomes de carbone ; or an E- (CH2) m- group, or E is a cycloalkyl residue containing from 3 to 6 carbon atoms or a pyridyl, furyl, thienyl, thiazolyl, oxazolyl, isoxazolyl group optionally substituted in the ring, and m is a number integer from 0 to 4; or a group EMI8.2 wherein X is hydrogen, lower alkyl or halogen; Y is hydrogen, lower alkyl, lower alkoxy, halogen, trifluoromethyl, cyano or alkanoyl containing 2 to 4 carbon atoms, and n is an integer from 0 to 4, Z is a radical alkylene comprising a straight chain of 1 to 5 carbon atoms; Ri est un atome d'hydrogène ou un radical alcoyle inférieur ; Ro est un radical alcoyle, alcényle ou cycloalcoyle contenant de 3 à 6 atomes de carbone ou un groupe pyridyle, pyridylalcoyle, furylalcoyle ou thiénylalcoyle, le radical alcoyle de ces derniers étant un radical alcoyle inférieur, et dans lesquels groupes le noyau peut porter un rad-cal alcoyle infé- rieur, ou un groupe EMI8.3 dans lequel X, Y et n ont la signification donnée plus haut, caractérisé en ce qu'on fait réagir une amine de formule NHRiR2 avec un acide de formule A-NHNHZCOOH ou un dérivé fonctionnel dudit acide. R 1 is a hydrogen atom or a lower alkyl radical; Ro is an alkyl, alkenyl or cycloalkyl radical containing from 3 to 6 carbon atoms or a pyridyl, pyridylalkyl, furylalkyl or thienylalkyl group, the alkyl radical of the latter being a lower alkyl radical, and in which groups the ring may bear a rad -cal lower alkyl, or a group EMI8.3 in which X, Y and n have the meaning given above, characterized in that an amine of formula NHRiR2 is reacted with an acid of formula A-NHNHZCOOH or a functional derivative of said acid. SOUS-REVENDICATIONS 1. Procédé selon la revendication, caractérisé en ce qu'on fait réagir l'amine avec un ester à une température pouvant atteindre jusqu'à environ 200"C et avantageusement comprise entre environ 600 et environ 2000 C. SUB-CLAIMS 1. Method according to claim, characterized in that the amine is reacted with an ester at a temperature which can reach up to approximately 200 "C and advantageously between approximately 600 and approximately 2000 C. 2. Procédé selon la sous-revendication 2, carac térisé en ce qu'on met en oeuvre un rapport au moins équimoléculaire des réactifs. 2. Method according to sub-claim 2, characterized in that an at least equimolecular ratio of the reactants is used. 3. Procédé selon la revendication, caractérisé en ce qu'on obtient le N-benzyl-p- (isonicotinylhydra- zine) propionamide en faisant réagir de la 1-isonicoti- nyl-2- (carbom6thoxy6thyl) hydrazine avec de la benzylamine. 3. Method according to claim, characterized in that one obtains N-benzyl-p- (isonicotinylhydrazine) propionamide by reacting 1-isonicotinyl-2- (carbom6thoxy6thyl) hydrazine with benzylamine. 4. Procédé selon la revendication, caractérisé en ce que, lorsque A est de l'hydrogène, on acyle le produit ainsi obtenu. 4. Method according to claim, characterized in that, when A is hydrogen, the product thus obtained is acylated.
CH7342559A 1958-07-17 1959-05-21 Process for the preparation of therapeutic compounds CH413856A (en)

Applications Claiming Priority (2)

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US74906158A 1958-07-17 1958-07-17
US784083A US2894972A (en) 1958-12-31 1958-12-31 Isonicotinylhydrazino alkanoic amides

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CH413856A true CH413856A (en) 1966-05-31

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CH (1) CH413856A (en)
DE (1) DE1420080A1 (en)
ES (1) ES249225A1 (en)
FR (1) FR460M (en)

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FR460M (en) 1961-05-02
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ES249225A1 (en) 1959-12-01

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