GB2067565A - Thio, sulphinyl and sulphonyl containing hydroxyamines and derivatives thereof - Google Patents

Thio, sulphinyl and sulphonyl containing hydroxyamines and derivatives thereof Download PDF

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GB2067565A
GB2067565A GB8105777A GB8105777A GB2067565A GB 2067565 A GB2067565 A GB 2067565A GB 8105777 A GB8105777 A GB 8105777A GB 8105777 A GB8105777 A GB 8105777A GB 2067565 A GB2067565 A GB 2067565A
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    • 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
    • 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
    • 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
    • A61K8/46—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds 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
    • A61Q5/008—Preparations for oily hair
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/008—Preparations for oily skin
    • 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

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

Abstract

Compositions for reducing or eliminating the greasy appearance of the hair and skin are disclosed which contain, as active ingredient, a novel compound of the general formula: <IMAGE> in which: n is 0, 1 or 2, R2 represents OH either a hydrogen atom or a radical which is: -CH2-CH2OH, <IMAGE> R3 represents either a hydrogen atom or a radical which is: -CH3 or -CH2OH, and R1 represents a radical which is: i) -CH3, ii) -CH2-CH = CH2, iii) -CH2-CH2OH, iv> <IMAGE> m being 1 or 2 and R4 representing a hydrogen atom or the radical -COR5, R5 being a saturated or unsaturated C1-8 aliphatic radical carbon atoms, v) -CH2-COR6, R6 representing a radical -OH or <IMAGE> r' and r'', which are identical or different, representing a hydrogen atom or a C1-5 alkyl radical, or r' and r'' together forming a divalent radical of the formula:- (CH2)2-O-(CH2)2- or of the formula: -(CH2)5- <IMAGE> R7 representing either the radical -NH2 or radical -COOH.

Description

1
SPECIFICATION
GB 2 067 565A 1 Compounds for use in cosmetic compositions for reducing or eliminating the greasy appearance of the hair and skin The present invention relates to compounds for use in cosmetic compositions for reducing or eliminating the greasy appearance of the hair and skin.
For the purpose of reducing the greasy appearance of the hair and skin, it has already been proposed to use thioethers derived from 8aminoethanethiol, in which the amine group is a primary amine group; the use of 2-(S-benzylthio)ethylamine hydrochloride has been particularly 10 suggested.
Completely surprisingly, it has been found, according to Application No. 79 20880, that the activity of some of these known compounds can be increased, and, furthermore, that their toxicity can be reduced, if the primary amine group is substituted by at least one alkyl radical carrying a hydroxyl group in the 8-position relative to the nitrogen atom. The excellent activity of 15 these compounds was completely unpredictable because the compounds substituted by nonhydroxylic alkyl radicals do not exhibit such activity.
In our Application No 79 20880 we describe and claim a cosmetic composition suitable for application to the hair and/or skin, this composition containing, in a suitable vehicle, at least one active ingredient corresponding to the following formula:
R2 1 R,-S-CH-CH2- N-CH2-CH-R, (1) 1 (0)n 1 OH in which: n is 0, 1 or 2, R, represents either a hydrogen atom or a radical which is: -CH2-CH20H, -CH2-CH-CH3 or -CH2-CH-CH20H, 1 1 OH Uti R3 represents either a hydrogen atom or a radical which is: -CH, or -CH, OH, and R, represents 35 a radical which is (i) -CH, (ii) -CH2-CH = CH2, 40 (iii) -CH,-CH,OH, (iv) -(CH2L-CH-COOH, 1 NH-R, m being 1 or 2 and R4 representing a hydrogen atom or the radical -COR, R, being a saturated 45 or unsaturated aliphatic, e.g. alkyl, radical having from 1 to 8 carbon atoms, (v) -CH2-COR,, R, representing a radical -OH or r 1 -N 1 r 11 r' and r", which are identical or different, representing a hydrogen atom or an alkyl radical 55 having from 1 to 5 carbon atoms, or r' and r" together forming a divalent radical of the formula: -(CH2)2-0-(CH2)2 or the formula: -(CH2),- 2 GB2067565A 2 (vi) -CH, and or:: 5 2 OL\ (viii) --/ ' j 1"7 R, representing either the radical -NH2 or the radical -COOH.
These active ingredients can be used either in the form of the free base or in the form of an 15 addition salt with an inorganic or organic acid; they can also be used as a mixture of these two forms.
Amongst the acids, there may be mentioned, in particular; hydrochloric acid, hydrobromic acid, tartaric acid, malic acid, nicotinic acid, salicylic acid, N-oxo-nicotinic acid, palmitic acid, gentisic acid, pyrrolidone-carboxylic acid, ascorbic acid, para-ch lorop hen oxyisob utyric acid, retinoic acid; (v-hydroxyisobutyric acid, a- and 8-hydroxybutyric acid, 5-amino-3-thiahexanedioic acid, pyruvic acid, glycolic acid, citric acid, aspartic acid, glutamic acid, oxoglutaric acid, camphosulphonic acid, thiodiglycolic acid and uronic acids.
Amongst the active ingredients which can be used in the compositions, the following may be mentioned in particular:
Compound No.: 1. N-(2-Methylthioethyi)-[3-hydroxyethylamine 2. N-(2Methyisulphinylethyl)-13-hydroxyethylamine 30 3. N-(2Methyisulphinylethyi)-bis-(2-hydroxyethyi)-amine 4. N-(2Methyisulphonylethyi)-bis-(2-hydroxyethyi)-amine 5. N-(2-M ethyl su 1 phi nylethyl)-b is-(2-hyd roxypropyl)-a m i ne 6. N-(2-Methyisulphinylethyi)bis-(2,3-dihydroxypropyi)-amine 7. N-(2-Ailyithioethyi)-bis-(2hydroxypropyi)-amine. 35 7a. N-(2-Aiiyithioethyi)-bis-(2hydroxypropyi)ammonium tartrate 7b. N-(2-Aiiyithioethyi)-bis-(2hydroxypropyl)-ammonium p-chlorophenoxyisobutyrate 8. N-(2Allyisulphinylethyi)-bis-(2-hydroxypropyi)-amine 9. N-(2-Aiiyithioethyl)bis-(2,3-dihydroxypropyi)-amine W. N-(2-Aiiyithioethyi)-bis-(2hydroxyethyl)ammonium glutamate 40 10. N-[2-(,8-Hydroxyethyithio)-ethyi]bis-(2-hydroxypropyi)-amine 11. N-[2-(#-Hydroxyethyisulphinyi)-ethyi]-bis(2-hydroxypropyi)-amine 12. 3-[2-(P-Hydroxyethylamino)-ethyithio]-alanine 13. 3-[2-(2-H yd roxypropyla m in o)-ethyith io]-a ia nine 14. 3-[2{Bis- (2-hydroxypropyi)-amino} -ethyithio]-alanine 45 15. 3-[2- {Bis-(2,3dihydroxypropyi)-amino} -ethylthio]-alanine 16. 2-Aceta m ido-3-[2-(2-hyd roxyethyla m in o)-ethyith io]-prop ionic acid 17. 2-Acetamido-3-[2-{bis(2-hydroxypropyi)-amino}-ethyithio]-propionic acid 18. 2-Acetamido-3-[2{bis-(2,3-dihvdroxypropyi)-amino}-ethyithio]-propionic acid 19. 2-Amino-4[2-(2-hydroxyethylamino)-ethy[thio]-butyric acid 50 20. 2-Amino-4-[2-{bis(2,3-dihydroxypi.,pyi)-amino}-ethyithio]-butyric acid 21. 2-Amino-4-[2-(2hydroxypropylamino)-ethyithio]-butyric acid 22. 2-Amino-4-[2-fbis-(2hydroxypropyi)-amino}-ethyithio]-butyric acid 23. 2-(2Hydroxyehylarriino)-f-.thyithioacetic acid 24. 2-[Bis-(2-hydroxypropyi)amino]-ethyithioacetic acid 55 25. 1\142-Morpholinocarbonyl methy[thioethyi)-bis-(2-hydroxyethyi)-a mine 26. N-(2Morpholinocarbonyimethyithioethyi)-bis-(2-hydroxypropyi)-amine 26a. N-(2Morpholinocarbonyimethyithioethyi)-bis-(2-hydroxypropyi)-amine hydrochloride 26b. N-(2-Morpholinecarbonyimethyithioethyi)-bis-(2hydroxypropyi)-ammonium pyruvate 26c. N-(2Morpholinocarbonyimethyithioethyi)-bis-(2-hydroxypropyi)-ammonium pchlorophe- noxyisobutyrate 26d. Di-[N-(2-morpholinocarbonyimethyithioethyi)-bis-(2hydroxypropyl)-ammonium] malate 26e. Di-[N-(2morpholinocarbonyimethyithioethyi)-bis-(2-hydroxypropyi)-ammonium] tartrate 27- N-[2-(o-Aminophenylthio)-ethyll-p-hydroxyethylamine 27a. N[2-(o-Aminopheny[thio)-ethyll-13-hydroxyethylammonium gentisate 27b. N-[2-(o-Aminophenyithio)-ethyll-jg-hydroxyethyiammonium pchlorophenoxyisobutyrate 65 W 1 -k 3 GB2067565A 3 27c. Di-[N-{2-(o-aminophenyithio)-ethyll-p-hydroxyethylammonium] malate, 27d. Di-[N-{2-(o-aminophenyithio)-ethyi}-,8-hydroxyethylammonium] tartrate 27e. N-[2-(o-Aminophenyithio)-ethyi]-,8-hydroxyethylammonium malate 28. N-[2-(o-Aminophenyithio)-ethyi]-bis-(2-hydroxyethyi)-amine 29. N-[2-(o-Aminophenyithio)-ethyi]-bis-(2,3-dihydroxypropyi)-amine 5 30. N-[2-(o-Aminophenyithio)-ethyi]-bis-(2-hydroxypropyl)-amine 31. 2-[2-(#-Hydroxyethylamino)-ethyithio]-benzoic acid 32. 2-[2-(,8-Hydroxyethylamino)-ethyisulphinyi]-benzoic acid 33. 2-[2-{Bis-(2-hydroxypropyi)-amino}-ethylthio]-benzoic acid 34. 2-[2-{Bis-(2-hydroxypropyi)-amino}-ethyisulphinyi]-benzoic acid 10 35. 2-[2- Bis-(2,3-dihydroxypropyi)-amino}-ethyithio]-benzoic acid 36. 2-[2-IBis-(2,3-dihydroxyproyi)-amino}-ethyisulphinyi]-benzoic acid 37. N-(2-Benzyithioethyi)-,8hydroxyethylamine 37a. N-(2-Benzyithioethyi)-P-hydroxyethylamine hydrochloride 38. N-(2-Benzy[thioethyi)-bis-(2-hydroxyethyi)-a mine 15 38a. N-(2-Benzyithioethyi)-bis-(2-hydroxyethyi)-amine hydrochloride 38b. N-(2-Benzy[thioethyi)-bis-(2-hydroxyethyi)-ammonium pyruvate 38c. N-(2-Benzyithioethyi)-bis-(2-hydroxyethyi)-ammonium pchlorophenoxyisobutyrate 38d. N-(2-Benzyithioethyl)-bis-(2-hydroxyethyl)ammonium pyrrolidonecarboxylate 38e. N-(2-Benzylthioethyi)-bis-(2-hydroxyethyl)-ammonium malate 20 38f. N-(2-Benzyithioethyi)-bis-(2-hydroxyethyi)-ammonium gentisate 38g. N-(2-Benzyithioethyi)-bis-(2-hydroxyethyi)-ammonium glucuronate 38h. N-(2-Benzyithioethyi)-bis-(2-hydroxyethyi)-ammonium 2-oxoglutarate 39. N-(2-Benzyithioethyi)-bis-(2,3-Dihydroxypropyi)-amine 40. N-(2-Benzyithioethyi)-bis-(2-hydroxypropyi)-amine 25 40a. N-(2-Benzylthioethyl)-bis-(2-hydroxypropyi)-a mine hydrochloride 40b. N-(2-Benzylthioethyl)-bis-(2-hydroxypropyi)-ammonium gentisate 40c. N-(2-Benzyithioethyi)-bis-(2-hydroxypropyl)-ammonium malate 40d. N-(2-Benzyithioethyi)-bis-(2-hydroxypropyl)-ammonium a- hydroxyisobutyrate 40e. N-(2-Benzyithioethyi)-bis-(2-hydroxypropyi)-ammonium pyruvate 30 40f. N-(2-Benzyithioethyl)-bis-(2-hydroxypropyi)-ammonium 2-oxoglutarate 40g. N-(2-Benzyithioethyi)-bis-(2-hydroxypropyl)-ammonium ascorbate 40h. N-(2-Benzyithioethyi)-bis-(2-hydroxypropyl)-ammonium 3- hydroxybutyrate 40i. N-(2-Benzyfthioethyl)-bis-(2-hydroxypropyi)-ammonium camphosulphonate 40j. N-(2-Benzyithioethyl)-bis-(2-hydroxypropyi)-ammonium 5-amino-3thiahexanedioate 35 40k. N-(2-Benzyithioethyi)-bis-(2-hydroxypropyi)-ammonium nicotinate 401. N-(2-Benzyithioethyi)-bis-(2-hydroxypropyf)-ammonium salicylate 41. N-(2-Benzyisulphinylethyi)-bis-(2-hydroxypropyi)-amine 42. N-(2-Benzyithioethyi)-N-(2-hydroxyethyi)2-hydroxypropylamine 42a. W(2-Benzyithioethyl)-N-(2-hyd roxyethyi)-2-hydroxypropyla mine hydrochloride. 40 43. N-(2Benzyithioethyi)-N-(2-hydroxyethyi)-2,3-dihydroxypropylamine The meanings of the radicals R, R2, R, and n in the compounds listed above are summarised in the following Table 1:
4 GB2067565A 4 TABLE 1
Compound: R,:R2: R3: n No. 5 1: -CH, H H 0 2:-CH3 H H 1 3 -CH,:-CH,,CH,OH H 1 4 -CH,:CH,CH,OH H 2 10 -CH,:-CH, CH-CH, -CH, 1 1 OH 6:-CH3-:-CH,-CH-CH20H -CH20H 1 1 15 OH 7 -CH2-CH = CHp,:-CH2-CH-CH3 -CH, 0 1 OH 8:-CH,-CH = CH2:-CH2-CH-CH3 -CH3 1 20 OH 9:-CH2-CH = CH2:-CH2-CH-CH,OH -CH20H 0 1 OH 25 10:-CH2-CH20H:-CH2-CH-CH, -CH3 0 1 OH k 11:-CH2-CH20H:-CH2-CH-CH3 -CH3 1 30 OH 12:-CH2- CH-COOH:H: H: 0 i NH2 13:-CH2- CH-COOH CH2-CH-CH3 H 0 35 NH2 OH 14 -CH2-CH-COOH:-CH2-CH-CH3 -CH3 0 1 1 NH2 OH 40 -CH2-CH-COOH:-CH2-CH-CH20H -CH20H 0 1 1 NH, OH 16: -CH2-CH-COOH:H: H: 0 1 45 NHCOCH, 17 -CH,-CH-COOH:-CH2-CH-CH3 -CH, 0 1 1 1 NHCOCH3 OH 18 -CH2-CH-COOH:-CH2-CH-CH20H -CH20H 0 50 NHCOCH, OH 19:-(CH2)2-CH-COOH:11 H 0 1 NH2 55 20:-(CHA2-CH-COOH:-CH2-OH-CH20H -CH20H 0 1 1 NH2 OH 21:-(CHA2-CH-COOH:H: -CH,: 0 1 60 NH2 22 -(CHI-CH-COOH:-CH,-CH-CH3 -CH, 0 1 1 NH2 OH 23:-CH2-COOH:H: H: 0 65 GB2067565A 5 TABLE 1 (continued) Compound: R,:R2: R3: n No.
24:-CH2-COOH -CH2CH-CH, -CH3 0 1 - OH 25 -CH 2 COI/-o:-CH2-CH20H H 0 10 \-i 26 15 -ell 2 CON 0 -CH2CH-CH3 -CH, 0 OH 20 27::H: H: 0 H 2 N 28:-CH2-CH20H H 0 25 29 -CH2CH-CH20H -CH20H 0 1 OH 30:-CH2-CH-CH, -CH3 0 1 30 OH 31 32 33 COOH v _ D 11:H 11 34 11 35 11 36 37 38 39 41 42 43 65 H: 0: -CH,: 0 -CH2CH-CH3 1 OH -CH2CH-CH3 1 OH -CH2CH-CH20H -CH20H i OH H COOH 0 :-CH2-C^:-CH2-C^:-CH2-C^ :-CH2-C^ :-CH2-C,^ :-CH2C6H5:-CH2C^ 1 : -CH3: 1 : 0 -CH2CH-CH20H -CH20H 1 1 OH :H: H: 0 -CH2CH20H H 0 -CH2CH-CH20H -CH20H 0 1 OH :-CH2-CH-CH, 1 OH :-CH2-CH-CH, 1 OH :-CH2-CH20H :-CH2-CH20H -CHz,: 0 -CH,: 1 -CH,: 0 -CH20H: 0 6 GB2067565A 6 If the active ingredient is acidic or basic, it can be neutralised in situ in the composition, either totally or partially, repectively with an inorganic or organic base or with an inorganic or organic acid, it being possible for the latter to be chosen, in particular, from amongst the acids mentioned above.
The present invention provides as new compounds, the compounds corresponding to the 5 following general formula:
R, 1 R,-S-CH,-CH,-N-CH,-CH-R, (0).
1 OH in which: n is 0, 1 or 2. R-, represents either a hydrogen atom or a radical which is:
-CH,-CH,OH, -CH-,-CH-CH, 1 OH and -CH2-CH-CH,OH, I Uri R, represents either a hydrogen atom or a radical which is: -CH, and - CH20H, and R, represents a radical which is:
2 5 (i) -CH, (ii) -CH,-CH = CH2, (iii) -CH,-CH,OH, (iv) -(CH,),-CH-COOH, 1 NH-R, m being 1 or 2 and R, representing a hydrogen atom or the radical -COR, R, being a saturated or unsaturated aliphatic, e.g. alkyl, radical having from 1 to 8 carbon atoms, (v) -CH2COR, R. representing a radical -OH or r 1 -N 11 r' and r", which are identical or different, representing a hydrogen atom or an alkyl radical having from 1 to 5 carbon atoms, or r' and r" together forming a divalent radical of the formula: -(CH2)2-0-(CH,-)2- or of the formula: (CH2),-, (vi) in which case R, only represents a 4 \_ hydrogen atom if R. represents a hydrogen atom, and (vii) ----J/ -- R, representing either the radical j R"-' 7 -Nil., or the radical -COOH, in which latter case R2 and R3 are not hydrogen atoms, and to the salts of the said compounds, with inorganic or organic acids such as those given above.
The present invention also provides a process for the preparation of these compounds. They 60 are generally prepared by reacting an oxirane with a compound of the formula (I]):
1 7 GB2067565A 7 P. 1 S -CH 2-CH2 -NH-R 2 + CH 2 -CH-R 3 \Y n (I 1) 0 5 2 -CH CH -12 11 CH-R R,-? 2--- 2 2-f- 3 n The oxirane used can be ethylene oxide (R3 = H), propylene oxide (R. = CH3) or glycidol (11, = -CH20H).
The addition reaction can be carried out in a variety of solvents but is preferably carried out in a polar solvent medium such as water or an alcohol, used alone or as a mixture.
If the radical R, contains an acid group, the latter is preferably neutralised beforehand with an 15 alkali metal hydroxide.
The addition reaction is suitably carried out at 0' to the boiling point of the solvent, depending on the oxirane used. It can also be brought to completion by leaving the reactants to stand for several days at ambient temperature.
The reaction product is generally isolated by concentrating the mixture under reduced 20 pressure, after neutralisation, if appropriate, with an acid. The resulting compound can optionally be purified by passing it over silica gel or over an ion exchange resin (if the reaction mixture contains inorganic salts) or by washing or by crystallisation using a suitable solvent.
The compounds of the formula (1) in which the radical R2 is the radical -CH2-CH-113 1 OH can be obtained directly from a compound of the formula (11) in which R2 = H by adding two 30 equivalents of oxirane.
Although the compounds of the formula (1) are preferably obtained in accordance with the process described above, they can also be obtained by reacting a hydroxyalkyl halide with a compound of the formula (11) in accordance with the following equation:
35 Ri-S -CH 2-CH2 -NH-R 2 X-CH 2 -CH-R 3 1 1 (0)n Vn 40 j2 R I- -CH 2-CH 2-N-CH 2 -CH-R 3 + XH (k AH X = Cl or Br. 45 The compounds, according to the invention, in which the radical R, = H and n = 0 can also be prepared by adding a thiol R,SH to a Whydroxyalkylaziridine in accordance with the 50 following equation:
R SH + H R S-CH CH NH-CH CH-R I- C2 2 1- 2- 2- 21 3 N OH 2 H -OH 3 8 GB2067565A 8 The reaction conditions are analogous to those relating to the reaction of an oxirane with a thioether.
If the thiol R,-SH contains a carboxylic acid group, the latter can optionally be neutralised prior to the reaction with the substituted aziridine.
In order to obtain the active ingredients in the form of a salt, it is generally possible to add, at ambient temperature, a solution of the active ingredient which it is desired to salify to an equirnolecular solution of the inorganic or organic acid corresponding to the desired salt.
The solvents used, which are identical or different, are generally alcohols or chlorohydrocar bons.
The mixture is generally stirred for about one hour and then concentrated under reduced 10 pressure. The evaporation residue is then washed with ether and finally dried at 50'C in vacuo over phosphorus pentoxide.
If diacids are used as the organic acid, it is possible to obtain, in a similar manner, either the mono-salt or the di-salt, depending on whether one mol of amine or two mols of amine are used, respectively, per mol of acid.
Activity of the compounds according to the invention In order to demonstrate the specific properties of the compounds according to the invention, epidermal lipid levels vvere determined following the repeated application of these compounds and were compared with the application of placebo solution and also with the application of 20 compounds possessing similar structures to the compounds of the formula (1). It is known that the greasy appearance of the skin or hair is related to the level of lipids present in the epidermis.
In order to ensure that these comparative determinations were of good statistical significance, the studies were carried out on a genetically stable and monitored subject, who had been conditioned beforehand by a specific diet in order to establish a characterised greasy (seborrheic) 25 condition, in accordance with the method described by AUBIN et al. in Parf. Cosm. Sav. France, 197 1, Volume 1, No. 8.
The substances tested were applied to the skin, at a concentration of 80 millimols per litre, for twelve consecutive days. The level of epidermal lipids was compared with that of the control subjects, of strictly equal age, who had received, with the same frequency, the same number of 30 applications of a control solution (water).
The comparative study involved the following compounds:
9 GB 2067 565A 9 Compounds. A. C,H5-CH2-S-CH2-CH2-NH2.HCI B. C6H5-CH2-S-CH2-CH2-NH-CH,.HCI C. C^-CH2-S-CH2-CH2-N CH, HCI CH3 10 D c 6 H 5-CH 2-S-CIT 2-CH2-le HCI E. C.H.-CH2-S-C112-C112-NO HCI F. C H -CH -S-CH -CH -N.2HCI 20 6 5 2 2 2 \_]H CH2-CH,OH 25 G. (No.: 38a) C,1-15-CH2-S-CH2-CH2-N HCI CH2-CH20H H. (No 37a) C,Hs-CH2-S-CH2-CH2-NH-CH2-CH20H. HCI 30 C1-12-CHOH-CH, 1. (No.:40a) C^-CH2-S-CH2-CH2-N / HCI 35 CH2CH01-1-CH3 The epidermal lipid measurements gave the following results, expressed in gg per Crn2 of skin (mean values):
U ntreated Seborrheic subjects treated with:
seborrheic subjects A B c D E F G H 1 45 2,098 1,710 1,972 2,622 2,706 2,496 2,979 1,469 1,490 1,637 A% - 18.5% - 6% + 25% + 29% + 19% + 42% 30% - 29% - 22% These results reveal that the substitution of the primary amine by a methyl radical (compound 50 B) almost completely nullifies the activity observed with compound A. The double substitution, by which compound A is converted to a tertiary amine, manifests itself, in the representative compounds C, D, E and F, in a considerable increase in the level of epidermal lipids, compared with the level observed with the seborrheic subjects to whom no substande has been applied.
This increase in the lipids ranges from + 19% to + 42%. On the other hand, and completely 55 unpredictably, the compounds according to the invention (compounds G, H and 1) give completely opposite results which are even lower than the most active reference compound (compound A).
The following Examples further illustrate the present invention.
PREPARATION EXAMPLES Example 1: 2-[2fl-Hydroxyethylamino)-ethytthiolbenzoic acid: Compound 31.
A solution of 6.16 9 of thiosalicylic acid in 60 mi of methanol is stirred at ambient GB 2 067 565A 10 temperature under a nitrogen atmosphere. A solution of 3.48 9 of N-(2- hydroxvethyl)-aziridine in 40 mi of methanol is added dropwise. The precipitate formed is filtered off and drained and the filtrate is concentrated. The residue obtained, together with the precipitate, is then crystallised from ethanol and this yields 9 9 of a white product which melts at 235'.
Analysis: CH,,NO,S Calculated % Found % C 54.75 H 6.26 N 5.80 S 13.28 54.58 6.20 5.68 13.05 Example 2: N-(2-Methylthioethyi)-fl-hydroxyetiylamine: Compound 1.
A mixture of W(2-hydroxyethyl)-aziridine (25.8 g) and sodium methanethiolate (21 9) in ethanol is heated the boil under a nitrogen atmosphere. When the reaction is complete, the mixture is neutralised with one equivalent of 5 N hydrochloric acid and then concentrated under reduced pressure. The residue is extracted with chloroform and then distilled after removal of 15 the solvent. 28 9 of a colourless oil which boils at 145' under a pressure of 26 mm Hq are collected.
Amine number: Calculated: 7.40 milliequivalents/g Found: 7.40 milliquivalents/g 20 Example 3 N-(2-Methyisulphinylethyl)-,8-hyd,-oxyethylamine: Compound 2. One equivalent of hydrogen peroxide is added dropwise to a solution of 13. 5 g of compound 25 1 (obtained in accordance with Example 2) in methanol, the temperature being kept below 3T. 25 When the reaction is complete, the solvent is evaporated off under reduced pressure and the residue is purified by filtration on silica gel. This yields 8 9 of a colourless oil which is a hemihydrate of compound 2.
Analysis: C^ffl,S. 1/2 H,0 30 Calculated % C 37.40 H 8.78 N 8.75 S20.00 Found % C 37.22 H 8.48 N 8.80 S20.25 Examples 4 and 5 3-N-[2-(,g-Hydroxyethylamino)-ethylti7io]-alanine: Compound 12 An aqueous-alcoholic solution of N-(2-hyd roxyethyl)-azi rid i ne (8.7 g) is added dropwise to a solution of cysteine (12.1 g) in 200 ml of 50% strength aqueous ethanol, under a nitrogen atmosphere. The temperature of the reaction mixture is kept at 45' for 4 hours and the mixture is then left to stand for 24 hours at ambient temperature. The mixture is filtered and the filtrate is concentrated under reduced pressure. The residue, taken up in ethanol, gives a crystalline 40 solid which is filtered off and drained. This yields 17 g of compound 12 which melts at 178'.
Analysis: C,H,,N20.S Calculated % C 40.36 H 7.74 N 13.45 S 15.59 Found % 40.34 7.69 13.40 15.41 45 Compound 16 is prepared under the same conditions, the cysteine being replaced by Nacetylcysteine. It is obtained in the form of a co'ouriess oil corresponding to a hernihydrate.
Analysis: C^^04S. 1 /2 H20 Calculated % C 41.68 H 7.38 1,1 10.80 S 12.36 Found % 41.66 7.25 10.84 12.43 Example 6
2-(2-Hydroxyethylamirio)-eL-I)ylthioacetic acid: Compound 23 An equimolecular mixture of ethyl thioglycolate and W(2-hyd roxyethyl)- azi rid i ne in methanol is heated at the boil for two hours under a nitrogen atmosphere. The reaction mixture is concentrated under reduced pressure and the residue is stirred in a 2 N aqueous solution of potassium hydroxide, containing a small amount ol ethanol. After 24 hours, the pH is brought to 4 by adding HCL The reaction mixture is concentrated under reduced pressure and the residue is dissolved in boiling ethanol. The crystals formed on cooling are filtered off and dried (yield = 50%). Melting point: 1 'i 0'.
1 11 GB2067565A 11 Analysis: C^.NO.S Calculated % Found % C 40.21 H 7.31 N 7.8 2 S 17.89 40.07 7.07 7.64 17.86 Example 7 N-[2-oAminophenylthio)-ethyll-fl-hydroxyethylamine: Compound 27 A methanolic solution of 3.48 g of N-(2-hydroxyethyl)-aziridine is added gradually to 5 g of oaminothiophenol, dissolved in methanol. After 72 hours at ambient temperature, the reaction mixture is concentrated and the residue, dissolved in benzene, is filtered on silica gel. This yields 10 8 9 of a pale yellow oil.
Analysis: C1,1-11,1\120S Calculated % Found % C 56.57 H 7.59 N 13.19 S 15.10 56.39 7.81 13.02 14.96 Examples 8 to 11 N-(2-Benzyithioethyl)-bis-(2-hydroxyethyi)-amine: Compound 38 A solution, heated to a temperature of 50', of 50 g of 2- benzyithioethylamine in 150 mi of absolute alcohol is placed in a reactor equipped with a brine condenser and a diffuser. After having purged the solution with a stream of nitrogen, a slow stream of ethylene oxide is passed 20 until it is no longer absorbed by the solution. Nitrogen is bubbled again, the solution is then concentrated under reduced pressure and the oily residue is dried over phosphorus pentoxide. This yields 74 9 of an oil, the analysis and the NIVIR spectrum of which correspond to the expected product.
Analysis: C,,1-1,1\102S Calculated % Found % C 61.14 H 8.29 N 5.49 S 12.56 60.93 8.34 5.64 12.40 Compounds 3, 4 and 25, obtained in the form of hygroscopic colourless oils, are prepared 30 under the same conditions.
Example Compound Yield Analysis: Calculated % No. % Found % 35 H N S 9 3 60 43.07 8.77 7.17 16.42 43.17 8.75 7.20 16.36 40 4 70 39.79 8.11 6.63 15.18 39.60 8.28 6.53 15.04 11 25 99 47.81 8.36 9.29 10.64 47.98 8.26 9.26 10.90 45 Example 12
N-(2-Benzylthioethyl)-bis-(2-hydroxypropyi)-amine: Compound 40.
Three equivalents of propylene oxide are added dropwise, whilst stirring, to a solution, cooled to 0', of 16.7 g of 2-benzyithioethylamine in 96' strength ethanol. The reaction mixture is 50 heated at 30' for six hours, it is then concentrated under reduced pressure and the residual oil obtained is dried in a desiccator containing phosphorus pentoxide.
28 g of a pale yellow oil are collected.
Analysis: C1,1-12,1\102S 55 Calculated % C 63.56 H 8.89 N 4.94 S 11.31 Found % 63.76 8.74 5.08 11.55 12 GB2067565A 12 Examples 13 to 24 N-(2-Methytsulphinylethyl)-bis-(2-hydroxypropyl)-amine: Compound 5 Three equivalents of propylene oxide are added dropwise, at a temperature below 10, and whilst stirring, to an aqueous solution of 2methyisulphinylethylamine (10. 7 g). The mixture is allowed to return to ambient temperature and is left to stand for 30 hours (the course of the reaction is followed by thin layer chromatography). It is then concentrated on a rotary evaporator and the residual oil is dried in a desiccator in vacuo and over phosphorus pentoxide. 21.5 9 of a colourless oil are thus obtained.
Analysis: C,H,,NO,S 10 Calculated % C 48.40 H 9.48 N 6.27 S 14.36 Found % 48.48 9.30 6.12 14.23 The compounds summarised in the following Table 11 are prepared in the same manner:
TABLE 11
Calculated % Analysis: Found % 20 Ex- Compound Yield ample: No. % 14 C: H N: S 16 17 19 24 7 8 10 11 17 24 21 22 26 33 (monohydrate) 23: 34 (dihydrate) : 41 (hemihydrate) 99 6711, 98 56.61 56.42 52.98 52.70 50.60 50.22 47.40 47.10 48.43 48.41 47.79 47.63 52.47 52.56 59.12 59.04 54.35 54.22 82(2) 49.29 49.53 58.41 58.77 40(2) 50(2) 90(3 98t3) 9811) 9.93 9.84 9.29 9.06 9.76 9.99 9.15 9.35 8.13 8.45 8.42 8.26 8.80 8.66 8. 50 8.29 7.60 7.60 7.44 7.82 8.49 8.42 6.00 5.94 5.61 5.44 5.90 5.59 5.52 5.74 8.69 8.65 5.57 5.39 8.74 8.87 9.84 9. 94 4.22 4.52 3.83 3.67 4.54 4.34 13.73 13.50 12.85 12.71 13.50 13.20 12.65 12.50 9.94 9.78 12.76 12.50 10.00 10. 13 11.27 11.29 9.67 9.74 10.39 9.87 (1) Purified by passage over silica ge-i.
(2) One equivalent of sodium hydroxide is added at the start of the reaction and one 50 equivalent of hydrochloric acid is added after the end of the reaction. The reaction mixture is filtered on an acid exchange resin.
(3) Reaction solvent: methanol.
Example 25 N-(2-Benzylthioethyl)-N-(2hydroxyethyl)-2-hydroxypropylamine:Compound 42 A mixture of 3.3 g of compound 37 in ethanol (30 mi), to which 1 9 of propylene oxide in water (15 mi) has been added, is left to stand for 24 hours. It is concentrated under reduced pressure and the residual viscous liquid is dried in a desiccator. This yields 3.8 9 of compound 42.
Amine number: Calculated 3.72 milliequivalents/g Found 3.72 milliequivalents/g 13 GB2067565A 13 Example 26
N-(2-Benzylthioethyl)-bis-(2,3-dihydroxypropyl)-amine: Compound 39 A mixture of 2-benzyithioethylamine (13 g) and excess glycidol (14.5 g) in toluene (200 m]) is heated at the boil for 3 hours; the product formed separates out in the form of an oil on cooling.
The latter is separated from the toluene phase and washed with benzene. 24.5 9 of compound 5 39 are thus obtained in the form of the monohydrate.
Amine number: Calculated Found 3.02 milliequivalents/g 3.02 milliequivalents/g Examples 27 and 28 N-(2-Methylsulphinylethyl)-bis-(2,3-dihydroxypropyl)- amine: Compound 6.
A solution of 14 g of 2-methylsulphinylethylamine and 19.5 g of glycidol in 50 ml of ethanol is heated at the boil for 8 hours. The reaction mixture is concentrated under reduced pressure and the oily residue obtained is purified by passing it over silica gel. 32 g of compound 6 are 15 collected.
Analysis: C,1-12,1\10,5S Calculated % C 42.33 H 8.29 N 5.49 S 12.56 Found % C 42.11 8.54 5.46 12.37 20 Compound 43, which is obtained with a yield of 60% in the form of the hemihydrate, is prepared in the same manner.
Analysis: Cl,H2,1\10,S. 1 /2 H,0 Calculated % C 57.06 H 8.15 N 4.75 S 10.89 Found % 56.98 8.13 4.63 10.57 Example 29
N-[2-(o-Aminophenylthio)-ethyl]-bis-(2,3-dihydrdxypropyl)-amine: Compound 29 A solution of 16.8 g of 2-(o-aminophenylthio)-ethyl-amine and 14.8 g of glycidol in 96' strength ethanol is left to stand for six days at ambient temperature. The reaction mixture is concentrated under reduced pressure and the oily residue is washed with toluene and then dried in a desiccator in the presence of phosphorus pentoxide. 29 g of compound 29 are thus obtained.
Analysis: C14H,,N204S Calculated % Found % C 53.14 H 7.64 52.88 7.61 N 8.85 S 10.13 8.76 9.94 Example 30 2-Acetamido-3-[2(bis-(2,3-dihydroxypropyl)-amino) - ethyithiol-propionic acid: Compound 18 A solution of 20.6 g of 2-acetamido-3-(,8-aminoethyithio)-propionic acid, 4 g of sodium hydroxide and 14.8 g of glycidol in 50% strength aqueous ethanol is heated for 7 hours at a temperature of 40. One equivalent ofhydrochloric acid is added and the mixture is purified by 45 passing it over an ion exchange resin (H -"). After evaporating off the solvent under reduced pressure, 19 9 of a viscous liquid, which crystallises in the form of a monohydrate melting at W, are obtained.
Analysis: C,3H2,N207S.H20 50 Calculated % C 41.92 H 7.58 N 7.52 S8.61 Found % 41.84 7.57 7.62 8.87 Example 31
5 2[2- (Bis-(2,3-dihydroxypropyl)-amino) -ethylsulphinyll-benzoic acid: Compound 36.
This compound is prepared in the same manner as compound 18 (Example 30) from glycidol and 2-(,8-aminoethyisulphinyl)-benzoic acid.
Preparation of 2-(fl-aminoethyisulphinyl)-benzoic acid A solution of 8.6 g of ethyleneimine in 200 m] of ethanol is added slowly, at 35', under a 60 nitrogen atmosphere, to an ethanolic solution of thiosalicylic acid (30.8 g). The 2-(,8-aminoethy] thio)-benzoic aid formed precipitates as the addition proceeds. It is filtered off and crystallised from a mixture of water and acetonitrile. This yields 37 g of crystals which melt at 120, (monohydrate) with formation of the anhydrous product which decomposes above 200'.
21.5 9 of this product are dissolved in acetic acid, and 10 mi of hydrogen peroxide of 110 65 14 GB2067565A 14 volumes strength are then added dropwise at 0'. The mixture is left to stand for 5 days at ambient temperature, it is then concentrated for 5 days at ambient temperature, it is then concentrated under reduced pressure and the residue is crystallised from water. 19.5 g of 2- (paminoethyisulphinyl)-benzoic acid, which melts at 240', are collected.
Analysis: C^1NO,S Calculated % Found % C 50.68 H 5.19 N 6.56 S 15.03 50.58 5.35 6.75 15.07 Compound 36 is obtained in the form of a yellow oil corresponding to a hemihydrate. 10 Analysis: Cl^,.NO,S. 1/2 H20 Calculated % C 48.63 Found % 48.60 H 6.52 N 3.78 6.89 3.71 EXAMPLES OF THE PREPARATION OF THE SALTS Example 32 N-(2-Benzyithioethyl)-bis-(2-hydroxyethyl)amine hydrochloride: Compound 38a.
A solution (45 m]) of 4 N hydrochloric acid in ethanol is added to an ethanolic solution of compound 38 (38 g). After two hours at ambient temperature, the solution obtained is concentrated and the residue is crystallised from 1,2-dichloroethane. After drying, 33 g of a compound which melts at 77' are collected.
Analysis: C,H22CINO2S Calculated % Found 1,0 C 53.50 H 7.6 0 N 4.80 S 10.99 53.33 7.58 4.57 10.82 Examples 33 and 34 30 N-(2-Benzylthioethyl)-bis-(2-hydroxypropyt)-amine hydrochloride: Compound 40a mi of a 4 N solution of hydrochloric acid in ethanol are added to 30 9 of compound 40, dissolved in chloroform. The mixture is left to stand for two hours at ambient temperature and 80 mi of ether are then added; compound 40a crystallises. After filtration and drying, 30 9 of crystals which melt at 95' are collected.
Analysis: C,^,C1NO,S Calculated 0,10: C 56.32 Found %: 56.32 1 i H 8.19 N 4.38 S 10.02 7.96 4.41 10.08 The hydrochloride 42a, which melts at 88', is obtained from compound 42 in accordance 40 with the same procedure.
Analysis: C14H.4CINO,S Calculated % Found % C 54.97 H 7.91 N 4.58 S 10.48 54.72 7.95 4.52 10.52 Examples 35 and 36 N-(2-Benzylthioethyl)-bis-(2--hydroxypropyl)-ammonium gentisate: Compound 40b.
A methanolic solution containing 4.6 9 of gentisic acid is added to 8.5 g of compound 40, dissolved in methanol, and the mixture is st-ed for 1 hour at ambient temperature. The solution obtained is concentrated under reduced pressure and the residue is filtered off and washed with ether. After drying, 12.9 g of white crystals which melt at 59' are obtained.
Analysis: C22H.ffi,S Calculated % Found % C 60.38 H 7.14 N 3.20 S7.32 60.38 7.16 3.41 7.34 Compound 27b is prepared in the same manner from compound 27 and butyric acid; it is obtained in the form of whitish crystals which melt at 58'.
Analysis: C,OH,,CIN204S Calculated % Found % C 56.26 H 6.3 7 N 6.56 S7.51 56.03 6.49 6.51 7.70 p-chlorophenoxyiso- Add GB 2 067 565A 15 Examples 37 to 59 The salts of compounds 7, 26, 27, 38 and 40, which are summarised in the following Table III, were also prepared in accordance with the same procedure as that described in Examples 32 to 36 (the salts are oily or semi-solid and strongly hygroscopic):
Ex- Compound Empirical ample: No.:formula TABLE Ill
Calculated % Analysis: Found % :C: H: N: S 37 7a C151-129N0,3S:46.98 46.75 38 7b C2,1-134CINO,S:56.29 56.00 39 26a C,,H29CIN204S:47.11 :46.94 26c C241-1,9CIN207S:52.11 M20 51.97 41 26d C32H62N4013S2:49.59 49.38 42 26e C32H62N4013S2:46,47 2H20:46.25 43 27a C,71-122N205S:55.72 55.53 44 27e C24HA407S2:51.59 51.57 27d C,41-122N2OGS:48.54 48.25 46 27e C24H3,3N4014S2:50.15 50.31 47 38b C161-12fNO6S:55.95 55.85 48 38c C23H32CINO5S:58.77 58.74 49 38d C,H28N205S:53.71 M20 53.88 38e C17H2-,NO.,S:52.42 52.25 51 38f C20H27NO6S:58.66 :58.86 52 389 C19H31NO9S:50.76 50.96 53 38h C1,1-127NO7S:51.53 H20 51.68 54 40c C1,1-131NO7S:54.65 54.75 55: 40d: C1,1-133NOrS:58.88 58.75 56 40e C1,,1-12,1\10rS:58.19 :58.10 57 40f C2,1-13,1\107S:53.67 M20 53.54 58 40g C2,1-133NO,S:52.81 M20 52.60 59 40h C,1-13,1\10,S:58.88 :58.75 7.62 7.67 7.64 7.46 8.19 8.31 7.47 7.46 8.06 8.36 8.04 8.09 6.05 6.16 6. 85 6.98 6.40 6.68 6.66 6.65 7.33 7.30 6.86 7.06 7.51 7.50 6.98 6.90 6.64 6.71 6.95 7.20 6.96 6.82 7.48 7.51 8.58 8.59 7.86 7.61 7.43 7.30 7.38 7. 36 8.58 8.24 3.65 3.38 3.12 2.93 7.85 7.73 5.06 4.84 7.22 7.12 6.77 6.81 7.64 7.72 10.02 10. 27 8.08 8.01 9.94 10.26 4.07 4.17 2.98 2.96 6.96 6.96 3.59 3.76 3.42 3.57 3.11 3.03 3.34 3.58 3.35 3.40 3.61 3.77 3.77 3.82 3.12 3.12 2.93 3.29 3. 61 3.48 8.36 8.13 7.15 6.98 8.98 8.90 5.79 6.08 8.27 8.32 7.75 8.05 8.75 8.58 11. 47 11.33 9.25 9.22 11.16 11.37 9.33 9.50 6.82 6.92 8.23 8.17 7.83 7.85 7.13 7.33 7.64 7.92 7.67 7.70 8.27 8.12 8.63 8.93 7. 16 7.33 6.71 6.73 8.27 8.38 16 GB2067565A 16

Claims (10)

1. A compound of the general formula:
R2 1 5 IR,-S-CH2-CH2-N-CH,-CH-R, (1) (0) 1 OH in which: n is 0, 1 or 2, R2 represents either a hydrogen atom or a radical which is -CH,-CH,OH, -CH2-CH-CH, or -CH2-CH-CH20H, i OH OH 15 R, represents either a hydrogen atom or a radical which 'S _Cl-13 or - C11201-1, and R, represents a radical which is i) -CH, 20 ii) -CH,-CH = CH, iii) -CH,-CH201-1, iv) -(C1-1j.-CH-COOH, 1 NH-R, 25 m being 1 or 2 and R, representing a hydrogen atom or the radical -COR, R5 being a saturated or unsaturated aliphatic radical having from 1 to 8 carbon atoms, v) -CH2COR,, R, representing a radical -OH or r 1 -N 1 rl' i r' and r", which are identical or different, representing a hydrogen atom or an alkyl radical having from 1 to 5 carbon atoms, or r' and r" together forming a divalent radical of the formula: -(C H2)2-0-(C H2)2- or of the formula: -(CH2)5-, vi) -CH-J/ \\ 2 \==/ in which case R2 can only represent a hydrogen atom if R3 represents a hydrogen atom, and vii) -p ' R, representing either the '7 50 radical -NH2 or the radical -COOH, in which latter case R2 and R3 are not hydrogen atoms.
2. Compound according to Claim 1 which is in the form of a salt with an inorganic or organic acid.
3. Compound according to Claim 2 in which the acid is hydrochloric acid, hydrobromic acid, tartaric acid, malic acid, nicotinic acid, salicylic acid, N-oxonicotinic acid, palmitic acid, ascorbic acid, parachlorophenoxyisobutyric acid, retinoic acid, a- hydroxyisobutyric acid, a- orfl-hydroxybutyric acid, 5-amino-3- thiahexanedioic acid, pyruvic acid, glycolic acid, citric acid, aspartic acid, glutamic acid, oxoglutaric acid, camphosulphonic acid, thiodiglycolic acid or a uronic acid.
4. Compound according to Claim 1 specifically identified herein. 60
5. Process for the preparation of a compound as claimed in any one of Claims 1 to 4, which 60 comprises reacting, in a polar solvent medium, an oxirane of the formula:
17 GB2067565A 17 CH -CH-R V/ 3 0 in which R, represents either a hydrogen atom or a radical which is: -CH3 or -CH20H, with a compound of the formula:
R,-S-CH2-CH2-NH-R, 1 (0).
in which: R, R2 and n are as defined in Claim 1.
6. Process according to Claim 5 which is carried out at a temperature of OT to the boiling point of the solvent.
7. Process for the preparation of a compound as claimed in any one of Claims 1 to 4 which comprises reacting a hydroxyalkyl halide of the formula:
X-CH2-CH-R3 1 OH in which: X represents a chlorine or bromine atom and R3 represents either a hydrogen atom or 25 a radical which is -CH, or -CH,OH, with a compound of the formula:
R,-S-CH,-CH2-NH-R2 1 (0).
in which: IR, R2 and n are as defined in claim 1.
8. Process for the preparation of a compound as claimed in any one of Claims 1 to 4 in which R, = H and n = 0, which comprises reacting, in a polar solvent medium, a thiol of the formula R,SH, in which R, is as defined in Claim 1, with a Whydroxyalkylaziridine of the 35 formula:
CH CH 2 CH 1 2 CH-OH 1 R3 in.which: R3 represents either a hydrogen atom or a radical which is -CH, or -CH,OH.
9. Process according to any one of claims 5 to 8 substantially as described in any one of Examples 1 to 59. 50
10. Compound as claimed in claim 1 whenever prepared by a process as claimed in any one 50 of claims 5 to 9.
Printed for Her Maiesty's Stationery Office by Burgess & Son (Abingdon) Ltd-1 9 8 1 Published at The atent Office, 25 Southampton Buildings, London, WC2A 'I AY, from which copies may be obtained.
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JPS5671021A (en) * 1979-11-16 1981-06-13 Lion Corp Preparation of agent for imparting iridescent luster
FR2476484A1 (en) * 1980-02-22 1981-08-28 Elf Aquitaine COMPOSITIONS FOR THE MOISTURIZATION OF KERATINIC SUBSTANCES CONSISTING OF ALPHA AMINO ACID SULFOXIDES
JPS60246307A (en) * 1984-05-22 1985-12-06 Shiseido Co Ltd Oil-in-water type emulsified cosmetic
JPS60246306A (en) * 1984-05-22 1985-12-06 Shiseido Co Ltd Water-in-oil type emulsified cosmetic
JPS60246308A (en) * 1984-05-22 1985-12-06 Shiseido Co Ltd Oily cosmetic
JPH0617293B2 (en) * 1985-04-17 1994-03-09 株式会社資生堂 Hair cosmetics
JPH03160125A (en) * 1989-11-17 1991-07-10 Nippon Carbureter Co Ltd Engine intake control valve device
DE19529773A1 (en) * 1995-08-12 1997-02-13 Beiersdorf Ag Weak, water-soluble mono:carboxylic acids used in skin care prepns. - as active agent for regeneration and promotion of the natural protective and barrier function of healthy or diseased skin

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US3341577A (en) * 1962-02-28 1967-09-12 Monsanto Res Corp Mercapto oxyalkyl amines
FR2285859A1 (en) * 1974-09-30 1976-04-23 Lafon Labor PHENYLSULFINYL-AMIDINES AND DERIVATIVES
FR2296406A1 (en) * 1974-12-31 1976-07-30 Oreal NEW COSMETIC COMPOSITIONS BASED ON SULFOXIDE DERIVATIVES OF CYSTEAMINE

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