CH513814A - New anti-seborrhoeic cpds - Google Patents

New anti-seborrhoeic cpds

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Publication number
CH513814A
CH513814A CH1740070A CH1740070A CH513814A CH 513814 A CH513814 A CH 513814A CH 1740070 A CH1740070 A CH 1740070A CH 1740070 A CH1740070 A CH 1740070A CH 513814 A CH513814 A CH 513814A
Authority
CH
Switzerland
Prior art keywords
radical
formula
free amine
amine group
hydrogen atom
Prior art date
Application number
CH1740070A
Other languages
French (fr)
Inventor
Kalopissis Gregoire
Original Assignee
Oreal
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Oreal filed Critical Oreal
Priority claimed from CH268869A external-priority patent/CH521754A/en
Publication of CH513814A publication Critical patent/CH513814A/en

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    • 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
    • C07D213/89—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 with hetero atoms directly attached to the ring nitrogen atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
    • A61K8/447—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof containing sulfur
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/008—Preparations for oily hair
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/23—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 nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
    • C07C323/24—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 nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C323/25—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 nitrogen atoms, not being part of nitro or nitroso 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 being acyclic and saturated
    • 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
    • C07D213/81—Amides; Imides
    • C07D213/82—Amides; Imides in position 3
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/02—Preparations for cleaning the hair

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Birds (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Anti-seborrhoeic cpds. of formula I and cosmetics, shampoos, and oral dispensible products contng. them. - R' and R" = the same or different H or alkyl - R3 = (CH2)pR6 (with p = 0-2, R6 = Ph, COOH, COOAlk, CMe3, CPh3, CH2NHR7, or CH(COOR8)NHR7 - where R7=H, acyl or sulphonyl, and R8 = H or alkyl) or R3 = 2-thienyl, 2-pyridyl, 2-N-oxy-pyridyl or a satd. or unsatd. straight or branched hydrocarbon radical up to C20 with opt. 1 or more hetero atoms or alcoholic functions, one of which is an end group. - R4 = H (in which case R5=(CH2)m COOH with m = 1-5, - y=x=1 when R3 contains no free NH2 or x=1, y=2 - when R3 contains 1 NH2 (free) group) or acyl or sulphonyl (in which case R5=Ph3C, Ph2CH or PhCH2 and y=x=1 when R3 has no free amino group or y=2, x=1 when R3 has 1 amino group or (CH2)m COOH with x=y=1 when R3 has 1 free amino grp. or x=2, y=1 when R3 has no free amino group) - n=0 or 1. - Anti-seborrhoeic agents for the treatment of hair and scalp as shampoos, gels, creams or aerosols; or for oral administration as pills, tablets, granules, with solid carriers or as solns. or capsules with liquid carriers.

Description

       

  Procédé de préparation de nouveaux sels organiques à action antiséborrhéique    La présente invention a pour objet un procédé<B>de</B> préparation de nouveaux sels utilisables en particulier comme  agents antiséborrhéiques correspondant à la formule générale suivante:  
EMI0001.0000     
    dans laquelle<B>:</B>  n<B>= 0</B> ou<B>1,</B>  RI et R2, identiques ou différents, représentent un  atome d'hydrogène ou un radical alcoyle inférieur,       R3    représente le groupement de formule:  - (CH2)p - R6 (p étant égal à 0, 1 ou 2),  dans laquelle R6 représente:

    .-C6H5, ou  .-COOH, ou  COOR (R représentant un radical alcoyle infé  rieur),  - C(CH3)3, ou C(C6H5)3 ou  -CH-NH-R7  (R7 représentant un atome<B>d'hy-</B>  drogène ou un radical acyle ou sulfonyle,  R8 représentant un atome d'hydrogène ou un radical  alcoyle inférieur), ou  - CH2 - NH - R7, ou  . le radical thiényle-2 de formule:  
EMI0001.0002     
    . le radical pyridyle-2, ou    . le radical (N-oxypyridyle)-2, de formule:  
EMI0001.0003     
    R3 représente un radical hydrocarboné saturé ou  insaturé, linéaire ou ramifié, comportant jusqu'à  20 atomes de carbone et présentant éventuellement  dans sa chaîne un ou plusieurs hétéroatomes et une  ou plusieurs fonctions alcool dont l'une peut être  terminale.  



  R4 représente:  <B>-</B> soit un atome d'hydrogène, auquel cas  R5 représente un radical - (CH2)m - C02H, In  étant un nombre entier variant de<B>1<I>à</I> 5,</B> et  <B>y</B>     =   <B>1</B> et x<B>= 1,</B> si     R3    ne renferme pas de grou  pement amine libre,  <B>y =</B> 2 et x<B>= 1,</B> si R3 renferme un groupement  amine libre,  - soit un radical acyle ou sulfonyle, auquel cas R5  peut être<B>:

  </B>  soit égal à (COH5)3C-1 (CA)2CH-,       CA   <B>-</B>     CH2   <B>- 1</B>      <B>y = 1</B> et x<B>= 1,</B> si     R,3    ne renferme pas de grou  pement amine libre,  <B>y =</B> 2 et x<B>= 1,</B> si R3 renferme un groupement  amine libre,  soit égal à -(CH2)m-CO2H,  .y = 1 et x = 1, si R3 renferme un groupement  amine libre,  <B>y = 1</B> et x<B>=</B> 2, si 11,3 ne renferme pas de grou  pement amine libre.  



  Parmi les composés actifs de ce type qui peuvent  être préparés par le procédé selon l'invention, on peut  citer:  - l'amino-5 carboxy-5 thia-3 pentanoate de     benzyl-          thio-2-éthylamine    de formule:  
EMI0002.0003     
    l'acétamido-5 thia-3 hexanedioate de     di(benzylthio-          2-éthylamine),    de formule:  
EMI0002.0006     
    l'amino-5 carboxy-5 thia-3 pentanoate de S-(amino-2  éthyl) 1-cystéine, de formule:  
EMI0002.0007     
    l'amino-5 carboxy-5 thia-3 pentanoate de     méthyl-          thio-2    éthylamine, de formule:

    
EMI0002.0010     
    l'amino-5 carboxy-5 thia-3 pentanoate de     benzyl-          thio-3    propylamine, de formule:  
EMI0002.0013     
    - l'amino-6 carboxy-6 thia-4 hexanoate de benzylthio-2  éthylamine, de formule:  
EMI0002.0014     
    l'amino-5 carboxy-5 pentanoate de (diméthoxy-2,     2-          éthylthio)-2    éthylamine, de formule:  
EMI0002.0017     
  
EMI0002.0018     
    - le N-acétyl S-benzyl 1-cystéinate de méthylthio-2  éthylamine, de formule:  
EMI0002.0019     
    le benzoylamino-5 thia-3 hexanedioate de     di(benzyl-          thio-2    éthylamine) de formule:

    
EMI0002.0022     
    le nicotinylamino-5 thia-3 hexanedioate de     di(benzyl-          thio-2    éthylamine) de formule:  
EMI0002.0025     
    le p-toluène sulfonylamino-5 thia-3 hexanedioate de  di(benzylthio-2 éthylamine) de formule:  
EMI0002.0026     
    le p-acétamidobenzènesulfonylamino-5 thia-3     hexane-          dioate    de di(benzylthio-2 éthylamine) de formule:  
EMI0002.0029     
    le p-acétamidobenzoylamino-5 thia-3 hexanedioate  de di(benzylthio-2 éthylamine) de formule:  
EMI0002.0030     
    - l'orthohydroxybenzoylamino-5 thia-3 hexanedioate de  di(benzylthio-2 éthylamine) de formule:  
EMI0002.0031     
      - l'acétamido-2 thia-4 heptanedioate de di(méthylthio-2  éthylamine) de formule:

    
EMI0003.0000     
    - l'amino-9 carboxy-9 thia-7 nonanoate de     benzyl-          thio-2    éthylamine, de formule:  
EMI0003.0003     
    - l'acétamido-2 thia-4 nonanedioate de thio-2,2'     bis-          (éthylamine)    de formule:  
EMI0003.0006     
    Le procédé selon l'invention est caractérsié par le  fait que l'on fait réagir au moins une base et au moins  un acide correspondant au sel<B>à</B> obtenir.  



  Pour la mise en ouvre du présent procédé, on peut  réaliser une solution ou une suspension de l'acide ou de  la base dans un solvant d'au moins un de ces deux cons  tituants, ajouter progressivement l'autre constituant sous  agitation, éventuellement en chauffant sous reflux, et  abandonner le mélange réactionnel pendant quelques  heures<B>à</B> une température comprise entre -20 et     +        5,)   <B><I>C.</I></B>  Dans ces conditions, le sel formé précipite ou cristallise.  



  La base est avantageusement utilisée en proportion  stochiométrique ou en léger excès par rapport à l'acide.  Afin d'illustrer l'invention, on va en donner main  tenant quelques exemples de mise en ouvre.  



  <I>Exemple<B>1</B></I><B> :</B>  Préparation de l'amino-5 carboxy-5 thia-3  pentanoate de benzylthio-2 éthylamine de formule:  
EMI0003.0009     
    Dans un ballon<B>de</B> 250 crus surmonté d'un réfrigérant  à reflux, contenant une suspension de 17,9 g de     S-carb-          oxyméthyl-1-cystéine    dans 95 cm3 de tétrahydrofuranne,  on introduit, sous agitation, 16,7 g de benzylthio-2     éthyl-          amine.     



  Le mélange est chauffé jusqu'à ébullition du solvant  puis on ajoute de l'eau goutte<B>à</B> goutte jusqu'à déclen  chement d'une forte réaction exothermique qui est sui  vie d'une prise en masse du mélange réactionnel. On  laisse reposer ensuite pendant une nuit<B>à -<I>100 C.</I></B>  



  Après filtration, le précipité qui s'est formé est rincé  au tétrahydrofuranne puis à l'acétone, essoré et séché  sous vide<B>à 500 C.</B>  



  On obtient ainsi 31,2 g d'amino-5 carboxy-5 thia-3  pentanoate de benzylthio-2 éthylamine.  



  Le composé obtenu fond entre 146 et 1480<B>C.</B>    L'analyse révèle qu'il contient 18,5 % en poids de  soufre, le pourcentage théorique de soufre étant de  18,55%.  



  Le composé obtenu est insoluble dans les alcools et  dans les solvants usuels, même<B>à</B> chaud. En revanche, il  est très soluble dans l'eau et en milieu hydroalcoolique.  <I>Exemple 2:</I>  Préparation de l'acétamido-5 thia-3 hexanedioate  de di(benzylthio-2 éthylamine) de formule:  
EMI0003.0014     
    Dans une fiole conique de 1OOcm3 contenant 0,05  mole/g d'acide acétamido-5 thia-3 hexanedioïque, en  solution dans 30cm3 d'éthanol absolu, on ajoute, goutte  à goutte, 0J mole de benzylthio-2 éthylamine, puis on  laisse reposer le mélange réactionnel pendant une nuit<B>à</B>  <B>-</B> 15o<B>C.</B>  



  L'acétamido-5 thia-3 hexanedioate de di(benzylthio-2  éthylamine) cristallise sous forme de fines aiguilles que  l'on filtre, lave<B>à</B> l'alcool absolu et sèche sous vide en  présence d'anhydride phosphorique.  



  Le rendement de la réaction est de 65 % .  



  Le produit obtenu se présente sous forme d'aiguilles  blanches présentant un point de fusion de 1200<B>C.</B>  



  Il est insoluble dans l'éthanol, mais très soluble dans  l'eau et en milieu hydroalcoolique.  



  <I>Exemple<B>3 :</B></I>  Préparation de l'amino-5 carboxy-5 thia-3 pentanoate  de S-(amino-2 éthyl) &alpha;-cystéine de formule:  
EMI0003.0015     
    On dissout 16,4 g de S-(amino-2 éthyl) &alpha;-cystéine  dans un mélange<B>de 250</B> cc de méthanol et<B>50 ce</B> d'eau.  Dans cette solution bien agitée et chauffée sous reflux  on introduit, par portions, 17,9 g de     S-carboxy-méthyl-          cystéine.    Le produit de salification précipite au fur et à  mesure. Le précipité est filtré, lavé avec du méthanol  absolu, puis séché. Le rendement est de 85 %.  



  Le composé obtenu est un solide blanc fondant<B>à</B>  <B>1860 C. Il</B> est soluble dans l'eau mais insoluble dans les  alcools.  



  <I>Exemple 4:</I>  Préparation de l'amino-5 carboxy-5 thia-3 pentanoate  de méthylthio-2 éthylamine, de formule:  
EMI0003.0018     
    En opérant comme indiqué dans l'exemple<B>3,</B> on fait  réagir 9g de S-carboxy-méthyl-cystéine sur 5g de     mé-          thylthio-2        éthylamine,    la réaction étant effectuée dans       l'éthanol.         Le produit obtenu est un solide blanc fondant<B>à</B>  205-210o     C     Il est soluble dans l'eau, insoluble dans l'éthanol et  dans les solvants usuels, mais soluble<B>à</B> chaud dans le  méthanol.  



  <I>Exemple<B>5:</B></I>  Préparation de l'amino-5 carboxy-5 thia-3 pentanoate  de benzytthio-3 propylamine, de formule:  
EMI0004.0001     
    En opérant comme indiqué<B>à</B> l'exemple<B>1,</B> on fait  réagir 8,9 g de S-carboxy-méthyl-cystéine sur 9,1 g de  benzylthio-3 propylamine, la réaction étant effectuée  dans l'éthanol.  



  On obtient<B>16,5 g</B> d'un solide blanc fondant<B>à 1290 C.</B>  <B>11</B> est soluble dans l'eau et soluble<B>à</B> chaud dans  l'éthanol.  



  <I>Exemple<B>6:</B></I>  Préparation de l'amino-6 carboxy-6 thia-4 hexanoate  de benzylthio-2 éthylamine de formule:  
EMI0004.0002     
    En opérant comme indiqué<B>à</B> l'exemple<B>1,</B> on fait  réagir 38,6g de S-carboxy-éthyl-cystéine sur 33,4g de  benzylthio-2 éthylamine, la réaction étant effectuée dans  l'éthanol.  



  On obtient<B>60,5 g</B> d'un solide blanc fondant<B>à</B> 95o<B>C,</B>  soluble dans l'eau et insoluble dans les alcools.    <I>Exemple<B>7:</B></I>  Préparation de l'amino-5 carboxy-5 thia-3 pentanoate  de (diméthoxy-2,2 éthylthio)-2 éthylamine,  de formule:  
EMI0004.0003     
    En opérant comme indiqué<B>à</B> l'exemple<B>3,</B> on fait ré  agir 17,9 g de S-carboxyméthylcystéine sur 18 g de     (di-          méthoxy-2,2    éthylthio)-2 éthylamine, la réaction étant  effectuée dans le méthanol absolu et<B>à</B> température or  dinaire.  



  On obtient 24<B>g</B> d'un solide blanc hygroscopique fon  dant entre<B>130</B> et 1400     C,    soluble dans l'eau, insoluble  dans l'éthanol et dans les solvants usuels et peu soluble  dans le méthanol.  



  <I>Exemple<B>8:</B></I>  Préparation du N-acétyl-S-benzyl &alpha;-cystéinate  de méthylthio-2 éthylamine, de formule:  
EMI0004.0007     
    En opérant comme indiqué<B>à</B> l'exemple 2, on fait  réagir 25,3 g de N-acétyl S-benzyl &alpha;-cystéine sur 9J g  de méthylthio-2 éthylamine, la réaction étant effectuée  dans l'éthanol.  



  On obtient<B>24g</B> d'un produit se présentant sous la  forme d'aiguilles blanches fondant<B>à 1310C</B> et soluble  dans l'eau et les alcools.



  Process for the preparation of new organic salts with antiseborrheic action The present invention relates to a process <B> for </B> the preparation of new salts which can be used in particular as antiseborrheic agents corresponding to the following general formula:
EMI0001.0000
    in which <B>: </B> n <B> = 0 </B> or <B> 1, </B> RI and R2, which are identical or different, represent a hydrogen atom or a lower alkyl radical, R3 represents the group of formula: - (CH2) p - R6 (p being equal to 0, 1 or 2), in which R6 represents:

    .-C6H5, or.-COOH, or COOR (R representing a lower alkyl radical), - C (CH3) 3, or C (C6H5) 3 or -CH-NH-R7 (R7 representing an atom <B> d 'hy- </B> drogen or an acyl or sulfonyl radical, R8 representing a hydrogen atom or a lower alkyl radical), or - CH2 - NH - R7, or. the thienyl-2 radical of formula:
EMI0001.0002
    . the pyridyl-2 radical, or. the (N-oxypyridyle) -2 radical, of formula:
EMI0001.0003
    R3 represents a saturated or unsaturated, linear or branched hydrocarbon-based radical, comprising up to 20 carbon atoms and optionally having in its chain one or more heteroatoms and one or more alcohol functions, one of which may be terminal.



  R4 represents: <B> - </B> either a hydrogen atom, in which case R5 represents a radical - (CH2) m - C02H, In being an integer varying from <B> 1 <I> to </ I > 5, </B> and <B> y </B> = <B> 1 </B> and x <B> = 1, </B> if R3 does not contain a free amine group, <B > y = </B> 2 and x <B> = 1, </B> if R3 contains a free amine group, - either an acyl or sulfonyl radical, in which case R5 can be <B>:

  </B> is equal to (COH5) 3C-1 (CA) 2CH-, CA <B> - </B> CH2 <B> - 1 </B> <B> y = 1 </B> and x <B> = 1, </B> if R, 3 does not contain a free amine group, <B> y = </B> 2 and x <B> = 1, </B> if R3 contains a group free amine, i.e. equal to - (CH2) m-CO2H, .y = 1 and x = 1, if R3 contains a free amine group, <B> y = 1 </B> and x <B> = </ B > 2, if 11.3 does not contain a free amine group.



  Among the active compounds of this type which can be prepared by the process according to the invention, there may be mentioned: - benzyl-2-ethylamine-5-amino-carboxy-5-thia-3 pentanoate of formula:
EMI0002.0003
    Di (benzylthio-2-ethylamine) acetamido-3-thia-3 hexanedioate, of the formula:
EMI0002.0006
    S- (2-aminoethyl) 1-cysteine 5-amino carboxy-5 thia-3 pentanoate, of the formula:
EMI0002.0007
    5-amino-5-3-methyl-thio-ethylamine-3-thia-pentanoate, of the formula:

    
EMI0002.0010
    5-amino-3-benzyl-3-thio-3-benzyl-thio-propylamine, of the formula:
EMI0002.0013
    - 6-amino-6-carboxy-4-benzylthio-2-ethylamine hexanoate, of formula:
EMI0002.0014
    (2-dimethoxy-2, 2-ethylthio) -2 ethylamine 5-amino carboxy-pentanoate, of the formula:
EMI0002.0017
  
EMI0002.0018
    - 2-methylthioethylamine N-acetyl S-benzyl 1-cysteinate, of formula:
EMI0002.0019
    di (2-benzyl-2-ethylamine) benzoylamino-3 thia-3 hexanedioate of the formula:

    
EMI0002.0022
    di (2-benzyl-2-ethylamine) nicotinylamino-3 thia-3 hexanedioate of the formula:
EMI0002.0025
    di (2-benzylthio-ethylamine) p-toluene sulfonylamino-3 thia-3 hexanedioate of the formula:
EMI0002.0026
    di (2-benzylthio-2-ethylamine) p-acetamidobenzenesulfonylamino-3-thia-3 hexane-dioate of the formula:
EMI0002.0029
    di (2-benzylthio-ethylamine) p-acetamidobenzoylamino-3 thia-3 hexanedioate of the formula:
EMI0002.0030
    - orthohydroxybenzoylamino-5 thia-3 hexanedioate de di (benzylthio-2 éthylamine) of formula:
EMI0002.0031
      - acetamido-2 thia-4 heptanedioate of di (2-methylthioethylamine) of formula:

    
EMI0003.0000
    - 9-amino-9-carboxy-7-thia-2-benzyl-2-ethylamine nonanoate, of formula:
EMI0003.0003
    - acetamido-2 thia-4 nonanedioate of thio-2,2 'bis- (ethylamine) of formula:
EMI0003.0006
    The process according to the invention is characterized in that at least one base and at least one acid corresponding to the salt <B> to </B> are made to react.



  For the implementation of the present process, it is possible to produce a solution or a suspension of the acid or of the base in a solvent of at least one of these two constituents, gradually adding the other constituent with stirring, optionally by heating under reflux, and leave the reaction mixture for a few hours <B> at </B> a temperature between -20 and + 5,) <B><I>C.</I> </B> Under these conditions , the salt formed precipitates or crystallizes.



  The base is advantageously used in a stochiometric proportion or in slight excess relative to the acid. In order to illustrate the invention, we will now give a few examples of its implementation.



  <I>Example<B>1</B></I> <B>: </B> Preparation of 5-amino-5-carboxy-3-benzylthio-3-ethylamine pentanoate of formula:
EMI0003.0009
    In a flask <B> of </B> 250 crus surmounted by a reflux condenser, containing a suspension of 17.9 g of S-carb-oxymethyl-1-cysteine in 95 cm3 of tetrahydrofuran, is introduced, with stirring , 16.7 g of 2-benzylthioethylamine.



  The mixture is heated until the solvent boils, then water is added dropwise until a strong exothermic reaction is triggered which is followed by a solidification of the mixture. reaction. It is then left to stand overnight at <B> at - <I> 100 C. </I> </B>



  After filtration, the precipitate which formed is rinsed with tetrahydrofuran and then with acetone, drained and dried under vacuum <B> at 500 C. </B>



  In this way 31.2 g of 5-amino-5-carboxy-3-benzylthio-3-ethylamine pentanoate is obtained.



  The compound obtained melts between 146 and 1480 <B> C. </B> Analysis reveals that it contains 18.5% by weight of sulfur, the theoretical percentage of sulfur being 18.55%.



  The compound obtained is insoluble in alcohols and in usual solvents, even <B> when </B> hot. On the other hand, it is very soluble in water and in hydroalcoholic medium. <I> Example 2: </I> Preparation of di (2-benzylthio-2-ethylamine) acetamido-3 thia-3 hexanedioate of formula:
EMI0003.0014
    In a 1OOcm3 conical flask containing 0.05 mole / g of 5-acetamidothia-3 hexanedioic acid, dissolved in 30cm3 of absolute ethanol, 0J mole of 2-benzylthioethylamine is added dropwise, then one let the reaction mixture stand overnight at <B> at </B> <B> - </B> 15o <B> C. </B>



  Di (2-benzylthioethylamine) acetamido-3-thia-3 hexanedioate crystallizes in the form of fine needles which are filtered, washed with absolute alcohol and dried under vacuum in the presence of phosphorus pentoxide.



  The reaction yield is 65%.



  The product obtained is in the form of white needles with a melting point of 1200 <B> C. </B>



  It is insoluble in ethanol, but very soluble in water and in hydroalcoholic medium.



  <I> Example <B> 3: </B> </I> Preparation of S- (2-aminoethyl) &alpha; -cysteine 5-amino-5-carboxy-3-thia-pentanoate:
EMI0003.0015
    16.4 g of S- (2-aminoethyl) &alpha; -cysteine are dissolved in a mixture of <B> 250 </B> cc of methanol and <B> 50 cc </B> of water. Into this well-stirred solution heated under reflux is introduced in portions, 17.9 g of S-carboxy-methyl-cysteine. The salification product precipitates as it goes. The precipitate is filtered off, washed with absolute methanol, then dried. The yield is 85%.



  The compound obtained is a white solid melting <B> at </B> <B> 1860 C. It </B> is soluble in water but insoluble in alcohols.



  <I> Example 4: </I> Preparation of 5-amino-5-carboxy-3-thia-2-methylthio-ethylamine pentanoate, of formula:
EMI0003.0018
    By operating as indicated in Example <B> 3, </B> 9 g of S-carboxy-methyl-cysteine are reacted with 5 g of 2-methylthioethylamine, the reaction being carried out in ethanol. The product obtained is a white solid melting <B> at </B> 205-210o C It is soluble in water, insoluble in ethanol and in usual solvents, but soluble <B> at </B> hot in methanol.



  <I>Example<B>5:</B> </I> Preparation of 5-amino-5-carboxy-3-benzytthio-3-propylamine pentanoate, of formula:
EMI0004.0001
    By operating as indicated in <B> in </B> Example <B> 1, </B> 8.9 g of S-carboxy-methyl-cysteine are reacted with 9.1 g of 3-benzylthio-propylamine, the reaction being carried out in ethanol.



  This gives <B> 16.5 g </B> of a white solid melting <B> at 1290 C. </B> <B> 11 </B> is soluble in water and soluble <B> at </B> hot in ethanol.



  <I>Example<B>6:</B> </I> Preparation of 6-amino-6-carboxy-4-benzylthio-2-ethylamine hexanoate of formula:
EMI0004.0002
    By operating as indicated in <B> in </B> Example <B> 1, </B> 38.6g of S-carboxy-ethyl-cysteine are reacted with 33.4g of 2-benzylthioethylamine, the reaction being carried out in ethanol.



  <B> 60.5 g </B> of a white solid melting at <B> at </B> 95o <B> C, </B> soluble in water and insoluble in alcohols is obtained. <I>Example<B>7:</B> </I> Preparation of (2,2-dimethoxy-ethylthio) -2-ethylamine 5-amino-5-carboxy-3-thia-pentanoate, of formula:
EMI0004.0003
    By operating as indicated in <B> in </B> Example <B> 3, </B> 17.9 g of S-carboxymethylcysteine are reacted on 18 g of (2,2-dimethoxyethylthio) -2 ethylamine, the reaction being carried out in absolute methanol and <B> at </B> standard temperature.



  24 <B> g </B> of a hygroscopic white solid melting between <B> 130 </B> and 1400 C, soluble in water, insoluble in ethanol and in the usual solvents and not very soluble in methanol.



  <I>Example<B>8:</B> </I> Preparation of 2-methylthio-ethylamine N-acetyl-S-benzyl &alpha; -cysteinate, of formula:
EMI0004.0007
    By operating as indicated in Example 2, 25.3 g of N-acetyl S-benzyl &alpha; -cysteine are reacted with 9J g of 2-methylthioethylamine, the reaction being carried out in 1 ethanol.



  <B> 24g </B> of a product is obtained in the form of white needles melting <B> at 1310C </B> and soluble in water and alcohols.

Claims (1)

REVENDICATION Procédé de préparation de sels utilisables en particulier comme agents antiséborrhéiques, de formule suivante: EMI0004.0008 dans laquelle<B>:</B> n<B>= 0</B> ou<B>1,</B> R, et R2, identiques ou différents, représentent un atome d'hydrogène ou un radical alcoyle inférieur, R3 représente le groupement de formule: - (CH2)p - R6 (p étant égal à 0, 1 ou 2), dans laquelle R. représente: CLAIM Process for preparing salts which can be used in particular as antiseborrheic agents, of the following formula: EMI0004.0008 in which <B>: </B> n <B> = 0 </B> or <B> 1, </B> R, and R2, identical or different, represent a hydrogen atom or a lower alkyl radical , R3 represents the group of formula: - (CH2) p - R6 (p being equal to 0, 1 or 2), in which R. represents: - c6H5, ou - COOH, ou COOR (R représentant un radical alcoyle infé rieur), ou -C(CH3)3, OU C(C6H5)3 ou -CH-NH-R7 <B><U>1</U></B> (X OR8 (R7 représentant un atome d'hy drogène ou un radical acyle ou sulfonyle, R8 représentant un atome d'hydrogène ou un radical alcoyle inférieur), ou <B>-</B> CH2 <B>- NH -</B> R7, <B>OU</B> le radical thiényle-2 de formule EMI0004.0012 <B>.</B> le radical pyridyle-2, ou . le radical (N-oxypyridyle)-2, de formule: - c6H5, or - COOH, or COOR (R representing a lower alkyl radical), or -C (CH3) 3, OR C (C6H5) 3 or -CH-NH-R7 <B> <U> 1 </ U > </B> (X OR8 (R7 representing a hydrogen atom or an acyl or sulfonyl radical, R8 representing a hydrogen atom or a lower alkyl radical), or <B> - </B> CH2 <B > - NH - </B> R7, <B> OR </B> the thienyl-2 radical of formula EMI0004.0012 <B>. </B> the pyridyl-2 radical, or. the (N-oxypyridyle) -2 radical, of formula: EMI0005.0000 R3 représente un radical hydrocarboné saturé ou insaturé, linéaire ou ramifié, comportant jusqu'à 20 atomes de carbone et pouvant présenter dans sa chaîne un ou plusieurs hétéroatomes et une ou plusieurs fonctions alcool dont l'une peut être ter minale. R4 représente: <B>-</B> soit un atome d'hydrogène, auquel cas: R, représente un radical -(CH2)m-CO2H, m étant un nombre entier variant de<B>1<I>à</I> 5,</B> et <B>y = 1</B> et x<B>= 1,</B> si R3 ne renferme pas de grou pement amine libre, <B>y =</B> 2 et x<B>= 1,</B> si R3 renferme un groupement amine libre, - soit un radical acyle ou sulfonyle, auquel cas R. EMI0005.0000 R3 represents a saturated or unsaturated, linear or branched, hydrocarbon-based radical comprising up to 20 carbon atoms and which may have in its chain one or more heteroatoms and one or more alcohol functions, one of which may be terminal. R4 represents: <B> - </B> either a hydrogen atom, in which case: R represents a radical - (CH2) m-CO2H, m being an integer varying from <B> 1 <I> to < / I> 5, </B> and <B> y = 1 </B> and x <B> = 1, </B> if R3 does not contain a free amine group, <B> y = </ B> 2 and x <B> = 1, </B> if R3 contains a free amine group, - either an acyl or sulfonyl radical, in which case R. peut être<B>:</B> soit égal à (C6H5)3C-, (C6H5)2CH-, C6H5 - CH2 -1 <B>y = 1</B> et x<B>= 1,</B> si R3 ne renferme pas de grou pement amine libre, <B>y =</B> 2 et x<B>= 1,</B> si R3 renferme un groupement amine libre, soit égal à - (CH2)m - C02H, <B>y = 1</B> et x<B>= 1,</B> si R3 renferme un groupement amine libre, <B>y = 1</B> et x<B>=</B> 2, si R3 ne renferme pas de grou pement amine libre, caractérisé par le fait que l'on fait réagir au moins une base et au moins un acide correspondant au sel<B>à</B> obtenir. can be <B>: </B> or equal to (C6H5) 3C-, (C6H5) 2CH-, C6H5 - CH2 -1 <B> y = 1 </B> and x <B> = 1, </ B> if R3 does not contain a free amine group, <B> y = </B> 2 and x <B> = 1, </B> if R3 contains a free amine group, i.e. equal to - (CH2) m - C02H, <B> y = 1 </B> and x <B> = 1, </B> if R3 contains a free amine group, <B> y = 1 </B> and x <B> = </B> 2, if R3 does not contain a free amine group, characterized in that at least one base and at least one acid corresponding to the salt <B> to </B> are made to react. SOUS-REVENDICATIONS <B>1.</B> Procédé selon la revendication, caractérisé par le fait que l'on réalise une solution ou une suspension de la base ou de l'acde dans un solvant d'au moins un de ces deux constituants, que l'on ajoute progressive ment l'autre constituant sous agitation, éventuellement en chauffant sous reflux, et que l'on abandonne le mé lange réactionnel pendant quelques heures<B>à</B> une tem pérature comprise entre<B>-</B> 200 et<B>+</B> 51, <B><I>C,</I></B> ce qui provo que la précipitation ou la cristallisation du sel. 2. Procédé selon la sous-revendication 1, caractérisé par<B>le</B> fait que l'on utilise la base en proportion st#chio- métrique ou en léger excès par rapport<B>à</B> l'acide. SUB-CLAIMS <B> 1. </B> Process according to claim, characterized in that a solution or a suspension of the base or of the acid in a solvent of at least one of these two is produced constituents, that the other constituent is gradually added with stirring, optionally by heating under reflux, and that the reaction mixture is left for a few hours <B> at </B> a temperature between <B > - </B> 200 and <B> + </B> 51, <B><I>C,</I> </B> which causes precipitation or crystallization of the salt. 2. Method according to sub-claim 1, characterized by <B> the </B> that the base is used in st # chemometric proportion or in slight excess with respect to <B> to </B> l 'acid.
CH1740070A 1968-02-23 1969-02-21 New anti-seborrhoeic cpds CH513814A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
LU55553 1968-02-23
CH268869A CH521754A (en) 1968-02-23 1969-02-21 Cosmetic composition containing novel antiseborrheic compounds

Publications (1)

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CH513814A true CH513814A (en) 1971-10-15

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