AU656625B2 - Alkanamidoammonium compound - Google Patents

Description

~r 1< 0I'I DATE 02/03/93 AOJ3P DATE 13/05/93 APPLN. ID 24027/92 H PTNUMBER PCT/JP92/01014 111Ilh~IIlII 11 ~HI~i AU9224027 C07C 235/10, A61 K 7/06

A

C07C 31'7/44, 323/60 A (43)1~D 131993k*211 18H (18 02 1993) (21) flF~thFi&t45 PCT,'J P92/01014 (74) ttN:h (22) 91 rit h F 19 92 _BfJ17 Ei 0 7. 0 8 9 2, 11U1'it KI TAGAWA, Toni z o %Yt tr-~ 3tt 4- k6 4 Tokyo, JP) ffNaF3/2 87 3 74 19 9 18A 0 3(l10. 08. 9 1) 3?1 (81) tMM (71)t RAC C 04A-.5E -z A T()i A U, B E WilV44 C A, C H(C IM49 tEF~~t±D E(D)*1,N D K E S FR (TAISHO PHARMACEUTICAL CO., LTD. )LJP.7JP) G BC $iI3 ,M G R Q-,M I E(PAi" 1) IT(I74 T171 TOMAEEE3TO24 i14j Tokyo, JP, KR.,U ii' C~4, (7 2) R NSt(; X Y S US.

WR~nCYOKOMORI. Sadakazu)CJP/JP) T336 T~3 7 1J+3 Saitlama., (JP') C%9* TAKAHASHI,Y u k i) CJP/J P) -2 024y_ Sa it ama, 0P) 662 EZ,47(MISANVA, Yoko)CJP/JP) 6 6 3 Sal tama, (31) *:2tPB(hATSUMOTO, T ar o) C JP/JP D Sai tama, (31) OL8IA% CHATAYAMA, K aI su o C JP/J P T 3 30 Y-t197 9ET1 200 0J_ 21 3 5 33 S a ita2rma, JP)1 (54) Title :ALKANAMIDOAMMONIUM COMPOUND (54) ROJ)k -7 J, t :1 7 F 7 E I L* -'PZ o R 3

R

R

1

R

2

R

4

-N+-R

6

I

L (I)

M

(57) Abstract An alkanamidoammonium compound, represented by general formula excellent in a trichogenic effect, wherein R1 represents alkyl or cycloalkyl; R2 represents alkylene; R 3 represents hydrogen or alkyl; R 4 represents alkylene; IRS and R 6 may be the same or different from each other and each represents alkyl; R 7 represents alkyl, alkenyl or phenylalk)I; A represents oxygen or wherein n represents an integer of 0 to 2; Xmn- represents an anion; and m represents an integer corresponding to the number of charges on the anion of X.

I

I

(57) 0

R

11 1 Ri-A-

R

2 C-N-R4

R

N

R

6 kXm m R 17 R 7&t

IL"

(0)n n i0 2CV [-Vc t7. A*:5 L PCT-Sst-~a L 6 W a L- I. 111M M IAI B1- I ftffl IL6 -V AT t Fl t MR-1)7zY AU V -3i )T FR 9' W .Y BB GA hf- NL N L 9 BE IL A- GB 'I i7 NO BJ HU' 1) PT .'l~a BR j9 i- IE -il RO -'Z CA b IT I P) RU i-3 JFt#Q P B* SD (Y CO KP~ V~llkb#n SE OH f KR*W I SK ;k 7 A. tQ CI i4lI U SN 4-,h L CS A LU L9 f 4'Yi TOD CZ :.3a~U MC t t TOI j-.3' ES MN .7

A

E746 1 45/2

DESCRIPTION

ALKANAMIDOAMMONIUM COMPOUNDS TECHNICAL FIELD The present invention relates to alkanamidoammonium compounds having a hair generating action.

BACKGROUND ART Compounds having structures and actions similar to those of the compounds of the present invention have not been known in the past.

DISCLOSURE OF THE INVENTION An object of the present invention is to provide a new type of compound having a hair generating action.

The present invention is an alkanamidoammonium compound represented by the formula: O R 3

R

I I i1

R

1 A- R 2 -C N R 4 N+ (I) j m L R7 [wherein R' is an alkyl group having 1 to 22 carbon atoms or a cycloalkyl group having 3 to 8 carbon atoms,

R

2 is an alkylene group having 1 to 15 carbon atoms, R 3 is a hydrogen atom or an alkyl group having 1 to r A i 2 carbon atoms, R 4 is an alkylene group having 2 to carbon atoms, R 5 and R 6 which may be the same or different, are each an alkyl group having 1 to 5 carbon atoms, R 7 is an alkyl group having 1 to 22 carbon atoms, an alkenyl group having 2 to 10 carbon atoms or an alkyl group having 1 to 5 carbon atoms substituted by a phenyl group, A is an oxygen atom or a group represented by the formula:

-S-

(0)n

(II)

(wherein n is an integer of 0 to X m is an anion and m is an integer corresponding to the number of electric charge of the anion for X].

In the present invention, the alkyl group having 1 to 22 carbon atoms refers to one which may be a straight or branched chain, for example, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, an n-pentyl group, an isopentyl group, a neopentyl group, a tert-pentyl group, an nhexyl group, an isohexyl group, an n-heptyl group, an noctyl group, an n-nonyl group, an n-decyl group, an nundecyl group, an n-dodecyl group, an n-tridecyl group, an n-tetradecyl group, an n-pentadecyl group, an nhexadecyl group, an n-heptadecyl group, an n-octadecyl group, an n-nonadecyl group, an n-icocyl group, an nre 3 henicosyl group and an n-docosyl group.

Examples of the cycloalkyl group having 3 to 8 carbon atoms are a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group and a cyclooctyl group.

The alkylene group having 1 to 15 carbon atoms refers to one which may be a straight or branched chain, for example, a methylene group, an ethylene group, a trimethylene oup, a tetramethylene group, a pentamethylene group, a hexamethylene group, an octamethylene group, a nonamethylene group, a decamethylene group, an undecamethylene group, a dodecamethylene group, a tridecamethylene group, a pentadecamethylene group, a propylene group, a 1-methyltrimethylene group, a 2,2dimethyl-trimethylene group, a 1-methyl-hexamethylene group, an ethylidene group, a propylidene group and a butylidene group.

The alkyl group having 1 to 5 carbon atoms refers to a straight or branched chain alkyl group, for example, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group and an n-pentyl group.

The alkylene group having 2 to 10 carbon atoms refers to one which has 2 to 10 carbon atoms among the alkylene group having 1 to 15 carbon atoms described above.

Examples of the alkenyl group having 2 to carbon atoms are a vinyl group, an allyl group, a 1- '-4 4 butynyl group, a prenyl group and a geranyl group.

The alkyl group having 1 to 5 caibon atoms substituted by a phenyl group refers to a straight or branched chain alkyl group substituted by a phenyl group, for example, a benzyl group, a phenylethyl group and a phenylpropyl group.

Examples of X" are anions of a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, sulfuric acid, nitric acid, nitrous acid, methyl sulfate, ethyl sulfate, dimethyl phosphate, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, formic acid, acetic acid, propionic acid, glycolic acid, lactic acid, oxalic acid, benzoic acid and salicylic acid.

The compounds of the present invention can be prepared, for example, by the following method (hereinafter symbols of R 1

R

2

R

3

R

4

R

5

R

6

R

7 A and n are as defined, unless otherwise especially indicated).

That is, a compound represented by the formula: R A R 2 COOH (III) is reacted with an amine represented by the formula:

R

HN R N

(IV)

I R

R

3

R

6 u

A

0" according to an amide forming reaction to give a compound represented by the formula:

R

R

I A- R 2 C N R 4 N (V) i s \3 6 0 R R 6 The amide forming reactions to be applied herein may be those under ordinary conditions, for example, a dehydration with heating, an acid halide method, a mixed acid anhydride method, an activated ester method and a carbodiimide method, but it is preferable to use the method of or The method of is carried out in the absence or presence of a solvent until one mole of water is eliminated. In the case of the absence of solvent, the reaction is usually carried out at a temperature of 130 to 200 0 C, preferably 150 170C, and in the case of the presence of a solvent, the reaction is carried out u 15 at a temperature of the boiling point of the solvent.

As the solvent can be used water-azeotropic solvents which do not give bad influence to the reaction, for example, xylene.

The method of comprises a reaction of the compound of Formula (IV) with an acid halide which is obtained by reacting the compound of Formula (III) with a halogenating agent. That is, the compound of Formula (III) is reacted with an equimolar amount to a large f '41: i 6 excess amount of a halogenating agent thionyl chloride, phosphorous pentachloride, phosphorous oxychloride, oxalyl chloride, thionyl bromide or phosphorous tribromide) in the absence of solvent or the presence of an inert solvent benzene, toluene, tetrahydrofuran, methylene chloride or chloroform) at room temperature to the boiling point of the solvent with stirring for 0.5 to 10 hours to give an acid halide of the compound of Formula (III), which is then reacted with a compound of Formula (IV) in the absence or presence of a solvent a halogenated hydrocarbon such as methylene chloride, chloroform or carbon tetrachloride, an ether such as diethyl ether, tetrahydrofuran or dioxane, an aromatic hydrocarbon such as benzene, toluene or xylene, an ester such as methyl acetate or ethyl acetate, a non-protonic polar solvent such as N,N-dimethylformamide or dimethyl sulfoxide) at about -30 to 100°C (preferably 0 to 500C). The first half of the reaction, although not always needing catalysts, can be accelerated by adding a catalytic amount to an equimolar amount of pyridine, triethylamine or N,N-dimethylformamide and the like.

Then, the compound of Formula is reacted with a compound represented by the formula: Y R 7

(VI)

S 25 (wherein Y is a halogen atom) or an acid ester having R 7 ml :i 7 in the absence or presence of a solvent according to a quaternization reaction to give a compound of the invention.

Examples of the halogen atom are a chlorine atom, a bromine atom and an iodine atom. Examples of the above-mentioned acid ester are mineral acid esters dimethyl sulfate, diethyl sulfate and trimethyl phosphate) and organic acid esters methyl methanesulfonate, methyl benzenesulfonate, methyl ptoluenesulfonate and pentyl p-toluenesu'fonate).

Examples of the solvent to be used are water, acetone, alcohols methanol and ethanol), diethyl ether, benzene and acetonitrile. The reaction temperature is from 0°C to 150°C (boiling point).

Additionally, the compound of Formula (I) wherein X m is a carboxylic acid formic acid, acetic acid, propionic acid, glycolic acid, lactic acid, oxalic acid, benzoic acid and salicylic acid) can be prepared by the following method. That is, the compound of the present invention obtained by the above-mentioned method is dissolved in a solvent, and ion-exchanged for various types types of formic acid, acetic acid, propionic acid, glycolic acid, lactic acid, oxalic acid, benzoic acid and salicyclic acid) of anion-exchange resin to give the desired compound.

Examples of the solvent to be used herein are water, alcohols methanol and ethanol) and a mixture thereof.

i aw.a-1% 8

I

k i On the other hand, the compound of Formula (I) wherein A is a group of Formula (II) and n is 1 or 2 can be also prepared by reacting the compound of Formula (V) [wherein A is a group of Formula (IV) and n is 0] obtained by the above method with 1 to 3 molar equivalents of an oxidizing agent in a solvent, followed by the same reaction as described above.

Examples of the oxidizing agent to be used herein are hydrogen peroxide and organic peracids (e.g.

peracetic acid, trifluoroperacetic acid, perbenzoic acid, perphthalic acid and m-chloroperbenzoic acid).

Examples of the solvent to be used are water, methylene chloride, chloroform, dichloroethane, benzene, toluence, ethyl acetate and acetic acid. The reaction temperature may be from -30 to 150 0

C.

Furthermore, the compound of Formula (I) wherein Xm- is an anion of a fluorine atom, a chlorine atom, a bromine atom, sulfuric acid, nitric acid or nitrous acid can be also prepared by the following method.

That is, the compound represented by the

I

V

formula: 0 R 3

R

II

R A R 2 C N R N Id P, F~ p/c'l

R

7

(VII)

r I c .i bl 9 (which is a compound of the present invention obtained by the above-mentioned method) is reacted with a silver salt capable of ion-exchanging for an iodine ion (e.g.

silver fluoride, silver chloride, silver bromide, silver sulfate, silver nitrate or silver nitrite) in a solvent at room temperature to the boiling point of the solvent to give a compound of Formula wherein Xm is an anion of a fluorine atom, a chlorine atom, a bromine atom, sulfuric acid, nitric acid or nitrous acid.

Examples of the solvent to be used are water, alcohols methanol and ethanol) and a mixture thereof.

The compounds of Formula (III) as the starting materials can be prepared from known compounds by the following methods.

In the case of the compound of Formula (III) v .erein A is a group of Formula (II) and n ii a thiol compound represented by the formula:

R

1 SH (VIII) "ild and a compound represented by the formula: Z' R 2 COOH (IX)

(Z

1 is a, halogen atom) in the presence of a base in a solvent are stirred at 0°C to the boiling point of the solvent for 0.5 to 10 hours to give a compound of 0 ;1 ii EB. RICE CO PATENT ATTORNEYS FBR/9-93/P1 L ur 4fr ffiLr 10 Formula (III) wherein A is a group of Formula (II) and n is 0.

Examples of the halogen atom are a chlorine atom, a bromine atom and an iodine atom. Examples of the base to be used are sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate and triethylamine. Examples of the solvent to be used are water, alcohols methanol and ethanol), acetone, N,N-dimethylformamide, acetonitrile, dioxane and tetrahydrofuran. Furthermore, a reaction accelerator such as potassium iodide can be also added.

In the case of the compound of Formula (III) wherein A is a group of Formula (II) and n is 1 or 2; the compound of Formula (III) [wherein A is a group of Formula (II) and n is 0] obtained by the method of the above is reacted with 1 3 molar amounts of an oxidizing agent to give a compound of Formula (III) wherein A is a group of Formula (II) and n is 1 or 2.

Examples of the oxidizing agent to be used herein are hydrogen peroxide and organic peracids (e.g.

peracetic acid, trifluoroperacetic acid, perbenzoic acid, perphthalic acid and m-chloroperbenzoic acid).

Examples of the solvent to be used are water, methylene chloride, chloroform, dichloroethane, benzene, toluene, ethyl acetate and acetic acid. The reaction temperature is from -30 to 1500C.

In the case of the compound of Formula (III) wherein A is an oxygen atom; an alcohol represented by different, are each an alkyl group having 1 to 5 carbon /2 11 the formula:

R

1 OH

(X)

and a compound represented by the formula:

Z

2

R

2 COOH (XI) (wherein Z 2 is a halogen atom) in the presence of a base in a solvent are stirred at 0 C to the boiling point for 1 48 hours to give a compound of Formula (III) wherein A is an oxygen atom.

Examples of the halogen atom are a chlorine atom, a bromine atom and an iodine atom. Examples of the base are sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydride, sodium amide, triethylamine, barium oxide and silver oxide. Examples of the solvent to be used are water, acetone, ether, tetrahydrofuran, N,N-dimethylformamide, dimethyl sulfoxide, 1,2-dimethoxyethane, acetonitrile and dioxane. Furthermore, a reaction accelerator such as potassium iodide may be also added.

A compound of Formula and a compound represented by the formula:

Z

3 R Z 4

(XII)

(wherein Z 3 and Z 4 which may be the same or different, 'i 12 are each a halogen atom) in the presence of a base in a solvent water, acetone, ether, tetrahydrofuran, N,N-dimethylformamide, dimethyl sulfoxide and 1,2dimethoxyethane) are stirred at 0°C to the boiling point of the solvent for 1 to 48 hours to give a halogenated ether, which is then reacted with magnesium, and the resulting Grignard reagent is reacted with carbon dioxide to give a compound of Formula (III) wherein A is an oxygen atom.

Examples of the halogen atom are a chlorine atom, a bromine atom and an iodine atom. Examples of the base to be used are sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydride, sodium amide, triethylamine, barium oxide and silver oxide.

Furthermore, the compound of Formula and a compound represented by the formula:

Z

5

R

2 CN (XIII) (wherein Z 5 is a halogen atom) in the presence of a base sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydride, sodium amide, triethylamine, barium oxide and silver oxide) in a solvent water, acetone, ether, tetrahydrofuran, N,N-dimethylformamide, dimethyl sulfoxide and 1,2dimethyoxyethane) are stirred at O0C to the boiling i point of the solvent for 1 to 48 hours to give an ether r +ti+ l 13 nitrile compound, which is then hydrolized to give a compound of Formula (III) wherein A is an oxygen atom.

Examples of the halogen atom are a chlorine atom, a bromine atom and an iodine atom. The above hydrolysis is carried out in the presence of an acid or base in a solvent at room temperature to the boiling point of the solvent with stirring for 1 to 12 hours.

Examples of the acid to be used herein are hydrochloric acid, sulfuric acid, acetic acid and formic acid, and examples of the base to be used are sodium hydroxide, potassium hydroxide and barium hydroxide. Examples of the solvent to be used are water and aqueous alcohols aqueous methanol and aqueous ethanol).

According to the amount and route of the administration of the compound of Formula one or more compounds of Formula can be formulated by using ordinary bases to give external dosage forms such as lotions, emulsions, creams, gels, aerosols, and can be applied in a suitable amount to the scalp several times a day. In these preparations may be contained other I pharmaceutically active substances.

As the ordinary bases described above and the other pharmaceutically effective substances, there can be used solvents ethyl alcohol, isopropyl alcohol, 1,3-butylene glycol, 1,4-butylene glycol, propylene glycol, dipropylene glycol, glycerol, diglycerol, polyethylene glycol, purified water), mucopolysaccarides hyaluronic acid, condroitin-4-sulfate, condroitin- Ifr 14 6-sulfate, dermatan sulfate, keratan sulfate, heparan sulfate and condroitin polysulfate), preservatives (e.g.

parabens and benzoic acid), vitamins vitamin A, vitamin BI, vitamin B 2 vitamin B 6 vitamin C, vitamin D, vitamin E and derivatives thereof vitamin E acetate)], oils liquid paraffin, white soft paraffin, solid paraffin, ceresin, microcrystalline wax, cholesterol, squalene, olive oil, rose hip oil, mink oil, jojoba oil, hydrogenated castor oil, hydrogenated coconut oil, isopropyl myristate, ethyl caproate, ethyl caprylate, palmitoleic acid, ethyl palmitolate, ethyl linolate, ethyl linolenoate, oleic acid, stearic acid, linoleic acid, linolenic acid, palmitic acid, behenic acid, lauric acid, stearyl alcohol, cetyl alcohol, lauryl alcohol, oleyl alcohol and cetyl isooctanoate), germicides sulfur, chlorhexidine hydrochloride, cetyl pyridinium chloride, chlorhexidine gluconate, chlorhexidine hydrochloride, cetyl pyridinium chloride, dequalinium chloride, isopropyl methyl phenol, 4 20 quaternary ammonium salts benzalkonium chloride) and hinokitiol], nonionic surfactants polyoxyethylene fatty acid esters, polyoxyethylene sorbitan fatty acid esters, sorbitan fatty acid esters, glycerol fatty acid esters, polyoxyethylene glycerol fatty acid esters, polyglycerol fatty acid ester, propylene glycol fatty acid esters, polyglycerol alkyl phenyl ethers, polyoxyethylene hydrogenated castor oil and copolymers r of polyoxyethylene and polypropylene glycol), anionic 1 ~LI -i I 1 15 surfactants N-acylamino acid salts, Nacylsarcosine salt, alkylphosphate salt and acylmethyltaurine salt), cationic surfactants (e.g.

alkyltrimethyl ammonium and alkyl-N,N-dialkylaminoacetic acid esters), amphoteric surfactants imidazoline and amineoxide), high-molecular surfactants (e.g.

casein), silicone derivatives silicone oil, polyol denatured silicone and silicone resin), thickers (e.g.

methylcellulose, polyvinylpyrrolidone, carboxymethylcellulose, carboxyethylcellulose, hydroxypropylcellulose and carboxyvinyl polymers), clay minerals (e.g.

montmorillonite, saponite and hectolite), pH regulators diisopropanolamine and citric acid), anti-oxidants dibutylhydroxytoluene, potassium hydrogen sulfite, catechin and gluconodeltalactone), whitening agents albutin and kojic acid), refrigerants Pmenthol and camphor), anti-inframmatory agents (e.g.

glycyrrhetic acid, dipotassium glycyrrhizinate, berberine chloride, shikonin, guaiazulene, allantoin and o-aminocaproic acid), peripheral vasodilators (e.g.

methyl nicotinate, benzyl nicotinate, swertiamarin, minoxidil, diazoxide, capsicum extract, capsicin and calpronium chloride), adrenocortical hormones (e.g.

hydrocortisone acetate and betamethasone valerate), antihistamines (diphenhydramine hydrochloride and isothipendyl hydrochloride), local anesthetics (e.g.

dibucaine hydrochloride and lidocaine hydrochloride), keratolytics urea and salicylic acid), kerato- *1 'Cl C -C

I

Room"q

C

ir 16 regulators vitamin A acid and derivative thereof 13-cis-retinoic acid and etoretinate)], estrogens 170-estradiol, ethynylestradiol and estrone), progestins progesterone and 17a-hydroxyprogesterone acetate), anti-androgens cyproterone acetate and 4-androstene-3-one-173-carboxylic acid), perfumes, sequestering agent, ultraviolet absorbents, moistening agents snake gourd extract, ginseng extract, diisopropyl acetate, pyrrolidone carboxylic acid, polyglutamic acid, polyoxyalkylenealkylglycoside ether, collagen, lecithin, ceramide, and 2-aminoethanesulfonic acid), crude drug extracts cashew extract, panax rhizome extract, lansic extract and saffran extract).

i n tit I i-

L

'C'

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4~ C 1~1~- BEST MODE OF CARRYING OUT THE INVENTION The present invention is further illustrated in more detail by the following preparation examples, examples and experiments.

(Examples) Preparation Example 1 ll-(Dodecylthio)undecanoic acid To a mixture of 101.2 g of dodecylmercaptan, 132.6 g of l1-bromoundecanoic acid and 300 ml of ethanol was added dropwise 120 ml of an aqueous solution of 40.0 g of sodium hydroxide at 60 C with stirring, followed by refluxing for 3 hours. After cooling, the mixture was I -I 1 1 -i I i I I.

-M

la~ 17 made acidic by adding 3N hydrochloric acid, extracted with chloroform, washed with water and a saturated aqueous sodium chloride solution successively, and dried over anhydrous sodium sulfate. After evaporation of the solvent, the product was recrystallized from chloroform to give 174.5 g of the title compound.

m.p. 69 71°C.

Following a substantially similar manner to that of Preparation Example 1 using the corresponding mercaptans and 11-bromoundecanoic acid, the following compounds were obtained.

11-(Isopentylthio)undecanoic acid m.p. 47 49 0

C.

1l-(Cyclohexylthio)undecanoic acid m.p. 46 480C.

11-(Decylthio)undecanoic acid m.p. 63 65 0

C.

Following a substantially similar manner to that of Preparation Example 1 using the corresponding 20 mercaptans and 3-bromopropionic acid, the following compounds were obtained.

3-(Tetradecylthio)propionic acid m.p. 66 68 0

C.

U4 .1i, 18 3-(Octadecylthio)propionic acid m.p. 78 80 0

C

Following a substantially similar manner to that of Preparation Example 1 using the corresponding mercaptans and 5-bromovaleric acid, the following compounds were obtained.

acid m.p. 59- 61 0

C.

acid m.p. 65 67 0

C.

acid m.p. 72 74 0

C.

Following a substantially similar manner to that of Preparation Example 1 using octadecylmercaptan and bromoacetic acid, the following compound was obtained.

(Octadecylthio)acetic acid m.p. 73 75 0

C.

<Following a substantially similar manner to that of Preparation Example 1 using octadecylmercaptan and 2-bromobutyric acid, the following compound was obtained.

1 19 2-(Octadecylthio)butyric acid m.p. 55 57 0

C.

Following a substantially similar manner to that of Preparation Example 1 using octadecylmercaptan and 2-bromopropionic acid, the following compound was obtained.

2-(Octadecylthio)propionic acid m.p. 65 67 0

C.

Preparation Example 2 3-(Tetradecylsulfonyl)propionic acid To a solution of 5.2 g of 3-(tetradecylthio)propionic acid obtained in Preparation Example 1 in ml of methylene chloride was added dropwise a solution of 8.9 g of m-chloroperbenzoic acid in 70 ml of methylene chloride at room temperature with stirring, followed by stirring at room temperature for a further 66 hours. The resulting crystals were collected by filtration, purified by silica gel column chromatography and recrystallized from ethyl acetate to give 2.5 g of 4 the title compound.

m.p. 136 138 0

C.

Following a substantially similar manner to that of Preparation Example 2 using 3-(octadecylthio)propionic acid obtained in Preparation Example 1, the following compound was obtained.

V..

1 i ^y blullmagilluia 3-(Octadecylsulfonyl)propionic acid m.p. 135 137°C Preparation Example 3 acid 56 ml of a 40% aqueous sodium hydroxide solution was added to 28.0 g of 1-tridecanol, 60.5 g of 1,4-dibromobutane and 0.4 g of tetra-n-butylammonium hydrogensulfate, followed by stirring at room temperature overnight. The mixture was extracted with ether, followed by drying over anhydrous magnesium sulfate.

Evaporation of the solvent under reduced pressure gave 11.7 g of l-(4-bromobutoxy)tridecane.

b.p. 148 149 0 C/0.80 mmHg.

To 2.4 g of magnesium were added 20 ml of tetrahydrofuran and a small peace amount of iodine, followed by reflux under an argon stream until the color of iodine was disappeared. To the reaction solution was added dropwise a solution of 26.8 g of the compound obtained in in 30 ml of tetrahydrofuran under reflux, followed by reflux for a further 30 minutes. To the reaction solution cooled to -5°C was added 150 g of dry ice to keep the temperature below o0C, followed by stirring at room temperature for an hour. 100 ml of sulfuric acid was added for hydrolysis, and the mixture was extracted with ether, and made basic with a aqueous sodium hydroxide solution. The aqueous layer i 5 S "l s .i 1 v

K)

P ;i r~ -i 1 21 was collected by fraction, made acidic again, extracted with chloroform and dried over anhydrous magnesium sulfate. Evaporation of the solvent under reduced pressure gave 11.8 g of the title compound.

m.p. 43 44°C Preparation Example 4 acid To a solution of 15.0 g of 1-tetradecanol in ml of tetrahydrofuran were added 12.2 ml of bromopentanenitrile and 4.9 g of a 96% potassium hydroxide powder under ice cooling. After stirring at room temperature for 24 hours, ethyl acetate was added, and the reaction solution was washed with a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. After evaporation of the solvent under reduced pressure, the residue was purified by silica gel column chromatography (eluent; ether nhexane 1:4) to give 7.4 g of pentanenitrile.

m.p. 30 31 0

C.

Following a substantially similar manner to that of Preparation Example 4(1) using 1-hexadecanol in place of l-tetradecano., the following compound was obtained.

t m.p. 40 41 0

C.

'1 1 fI L i -irL i -i -I i'i i. :I-1 I_ r

K

22 Following a substantially similar manner to that of Preparation Example 4(1) using 1-octadecanol i.n place of 1-tetradecanol, the following compound was obtained.

m.p. 46 47 0

C.

To a solution of 8.6 g of the compound obtained in in 50 ml of ethanol was added 50 ml of a aqueous potassium hydroxide solution, followed by reflux for 8 hours. After cooling, the mixture was made acidic by addir. conc. hydrochloric acid, extracted with ethyl acetate, washed with a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate. Evaporation of the solvent under reduced pressure gave 8.6 g of the title compound.

m.p. 56 57°C Following a substantially similar manner to that of Preparation Example the following compounds were obtained.

5-(Hexadecyloxy)valeric acid m.p. 64 65 0

C.

acid m.p. 68 69 0

C.

I a

L

23 Preparation Example N-F3-(Dimethylamino'propyll-11- (dodecylthio)undecanamide 150.0 g of 11-(dodecylthio)undecanoic acid obtained in Preparation Example 1 and 47.6 g of N,Ndimethyl-1,3-diaminopropane in 200 ml of xylene were refluxed for 5 hours while the forming water was kept removing. After cooling, the product was collected by filtration, and recrystallized from methyl ethyl ketone to give 153.3 g of the title compound.

m.p. 68 70 0

C.

Following a substantially similar manner to that of Preparation Example 5 using N,N-diethyl-1,3diaminopropane in place of N,N-dimethyl-1,3diaminopropane, the following compound was obtained.

N-[3-(Diethylamino)propyl]-11-(dodecylthio)undecanamide m.p. 59 61 0

C.

Following a substantially similar manner to that of Preparation Example 5 using N,N-diethyl-1,2ethylenediamine in place of N,N-dimethy-1,3diaminopropane, the following compound was obtained.

N-[2-(Diethylamino)ethyl3-11-(dodecylthio)- I i Ix

I

i~ undecanamide m.p. 63 65 0

C.

4.

4: 24 Following a substantially similar manner to that of Preparation Example 5 using N,N-dimethyl-1,2ethylenediamine in place of N,N-dimethyl-1,3diaminopropane, the following compound was obtained.

N-[2-(Dimethylamino)ethyl]-11-(dodecylthio)undecanamide m.p. 71 730C.

Following a substantially similar manner to that of Preparation Example 5 using N,N-dimethylneopentanediamine in place of N,N-dimethyl-1,3diaminopropane, the following compound was obtained.

N-[2,2-Dimethyl-3-(dimethylamino)propyl]-11- (dodecylthio)undecanamide m.p. 59 61 0

C.

Following a substantially similar manner to that of Preparation Example 5 using the compounds obtained by a similar manner to that of Preparation Examples 1 4 in place of 11-(dodecylthio)undecanoic acid, the following compounds were obtained.

N-[3-(Dimethylamino)propyl]-11- (isopentylthio)undecanamide m.p. 47 49 0

C.

N-[3-(Dimethylamino)propyl]-11- (cyclohexylthio)undecanamide m.p. 61 63 0

C.

1. r" v reV 3-(Dimethylamino)propyl]-11-(decylthio)undecanamide rn-p. 62 64 0

C.

N- (Dimethylamino )propyl 3-3- (tetradecylthio )propanamide m-p. 46 48 0

C.

N- Dimethylamino )propyl (tetradecylsulfonyl )propanamide m.p. 89 910c.

decylthio )pentanamide m-p. 58 60 0

C.

N- (Dimethylamino )propyl 3-5- (hexadecyithi pentanamide m.p. 68 70 0

C.

N- (Dimethylamino )propyl] (octadecyithic) acetamide m.p. 53 -55 0

C.

N- (Dimethylamino )propyl 3-3- (octadecyithi propanamide m.p. 58 -600C.

-26 N- (Dimethylamino )propyl 1-3- (octadecylsulfonyl )propanamide M.P. 98 100*C.

N- (Dimethylamino )propyl]-5- (octadecyithic) pentanamide m.p. 68 701C.

N- (Dimethylamino )propyl 1-5- (tetradecyloxy) pentanamide m.p. 53 541C.

N-[3-(Dimethylamino)propyl]-5- (tridecyloxy)pentanamide m.p. 46 471C.

N- (Dimethylamino )propyl 1-5- (hexadecyloxy) pent anamide m.P. 58 59'C.

N- (Dimethylamino )propyl 1-5- (octadecyloxy) pentanamide M.P. 66 67 0

C.

Following a substantially similar manner to that of Preparation Example 5 using the compounds obtained by a similar manner to that of Preparation Examples 1 -4 and N,N-dimethyl-l,2-ethylenediamine in b 11: 4 i. r 27 place of 11-(dodecylthio)undecanoic acid and N,Ndimethyl-1,3-diaminopropane respectively, the following compounds were obtained.

pentanamide m.p. 58 59 0

C.

pentanamide m.p. 72 74 0

C.

I3 pentanamide m.p. 52 53 0

C.

Preparation Example 6 N- 3-(Dimethylamino)propyl1-3-(methylthio propanamide To a solution of 4.3 g of 3-(methylthio)propionic acid in 40 ml of toluene was added 8.5 g of thionyl chloride, followed by stirring at 80 0 C for 3 hours. The toluene and excess thionyl chloride were evaporated under reduced pressure. A solution of the resulting crude chloride in 10 ml of chloroform was added dropwise to a solution of 3.7 g of N,N-dimethyl- 1,3-diaminopropane in 20 ml of chloroform under ice cooling with stirring, followed by stirring at room ,'025 temperature for a further 16 hours. The reaction 0 r e 1 1 1 1 I 1 :rn i; -I I r I I C i 1 L. i I 1-~1 t' Fi- 28 solution was washed with a saturated aqueous sodium bicarbonate solution, water and a saturated aqueous sodium chloride solution successively, and dried over anhydrous sodium sulfate. Evaporation of the solvent under reduced pressure gave 6.0 g of the title compound as an oily liquid.

1H-NMR(CDC13) 6(ppm); 1.75 (2H, quint., J=6.3Hz), 2.14 (3H, 2.35 (6H, 2.43 2.61 (4H, 2.80 (2H, t, J=6.9Hz), 3.37 (2H, quart., J=6.0Hz), 7.22 (1H, br. s) Preparation Example 7 N-r3-(Dimethylamino)propyll-11-(dodecylsulfinvl)undecanamide To a solution of 1.0 g of N-[3-(dimethylamino)propyl]-ll-(dodecylthio)undecanamide obtained in Preparation Example 5 in 50 ml of chloroform was added dropwise a solution of 0.5 g of m-chloroperbenzoic acid in 15 ml of chloroform under ice cooling with stirring, followed by stirring under ice cooling for a further 4 hours. The reaction solution was washed with a saturated aqueous sodium bicarbonate solution, water and a saturated aqueous sodium chloride solution successively, and dried over anhydrous sodium sulfate. After evaporation of the solvent under reduced pressure, the product was recrystallized from chloroform ether to give 0.91 g of the title compound.

A m.p. 110 112 0

C.

V- CIi

I

I-t :i :rt 29 Example 1 N- 3-[11-(Dodecylthio)undecanamidolpropyl}- N,N,N-trimethylammonium iodide To a solution of 120.0 g of N-[3- (dimethylamino)propyl]-ll-(dodecylthio)undecanamide obtained in Preparation Example 5 in 1 Q of ethanol was added 52.4 g of methyl iodide, followed by stirring at room temperature for 3 days. The product was collected by filtration and recrystallized from ethanol to give 141.5 g of the title compound.

m.p. 103 105 0

C

'H-NMR(CDCl 3 S(ppm); 0.88 (3H, t, 1.19 1.71 (36H, 2.06 2.24 (2H, m), 2.32 (2H, t, J=7.5Hz), 2.50 (4H, t, J=7.4Hz), 3.32 3.49 (11H, 3.80 3.93 (2H, m), 7.30 7.41 (1H, m) Following a substantially similar manner to that of Example 1 using the corresponding amides obtained by a similar manner to that of Preparation Examples 5 7 in place of N-[3-(dimethylamino)propyl]l1-(dodecylthio)undecanamide, the following compounds were obtained.

N-{3-[3-(Methylthio)propanamido]propyl}-N,N,Ntrimethylammonium iodide m.p. 118 120 0

C.

x [N-{2-[N'-Mety3-(yl-3-(methylthio)propanamido]- L ~L I. il 1~ Jr 30 ethyl}-N, N, N-trimethylammonium iodide M.P. 132 134 0

C.

11- (Isopentylthio)undecanamido]propyl}- N,N,N-trimethylammonium iodide M.P. 98 100*C.

N{ 3-[li- (Cyclohexylthio )undecanamido ]propyl}- N,N,N-trimethylammonium iodide m.p. 101 1031C.

11-(Decylthio)undecanamido]propyl}- N,N,N-trimethylammonium iodide M.P. 99 1011C.

11-(Dodecylthio)undecanamido]ethyl}- N, N,N-trimethylarnmonium iodide m.P. 115 1170C.

N- [11- (Dodecylthio )undecanamido ]ethyl Ndiethyl-N-methylammonium iodide m.p. 75 77 0

C.

r 3, 11- (Dodecylsulfinyl)undecanamido]propyll}-N, N, N-trimethylammonium iodide m.P. 123 125 0

C.

3- [11- (Dodecylthio )undecanamido ]propyl}- -31 N, N-diethyl-N-methylamnonium iodide M.P. 88 90 0

C.

2-Dimethyl-3-[11-(dodecylthio)undecanamido ]propyl N-trimethylainmonium iodide m.P. 127 129 0

C.

(Tetradecylthio )propanamido Ipropyl}- N,N,N-trimethylaxnmonium iodide M.p. 116 118 0

C.

N- (Tetradecylsuif onyl )propanamido] propyll}-N, N, N-trimethylammonium iodide m.p. 76 78 0

C.

(Tetradecylthio )pentanamido lpropyl}- N, N,N-trimethylanunonium iodide m.p. 91 931C.

N- (Hexadecylthio )pentanamido]propyl}- N,N,N-trimethylammoniumf iodide m.p. 95 97 0

C.

(Octadecylthio )propanamido ]propyl}- N, N,N-trimethylammonium iodide M.p. 116 1181C.

(Octadecylsulfonyl )propanamido] 32 propyl}-N,N,N-trimethylammonium iodide m.p. 96 98 0

C.

N-{3-[2-(Octadecyithio)propanamido]propyl- N,N,N-trimethylammonium iodide m.p. 131 133 0

C.

N,N,N-trimethylammonium iodide m.p. 88 90 0

C.

N,N,N-trimethylammonium iodide m.p. 96 98 0

C.

Example 2 N- N,N,N-trimethvlammonium iodide To a solution of 2.5 g of N-[3-(dimethylobtained by a similar manner to that of Preparation Example 5 in 10 ml of ethanol was added 0.6 ml of methyl iodide, followed by stirring at room temperature for 24 hours. After evaporation of the solvent under reduced pressure, the product was recrystallized from ethanol ether to give 2.9 g of the title compound.

m.p. 94 96 0

C.

1 H-NMR(CDCl 3 6(ppm); 0.88 (3H, t,

AS,

33 1.26 (22H, 1.46 1.78 (6H, i) 2.03 2.22 (2H, in), 2.34 (2H, t, J=7.OHz), 3.32 3.48 (15H1, in), 3.78 3.91 (2H, in), 7.17 7.27 (1H1, mn) Following a substantially similar manner to that of Example 2 using the corresponding amnides in place of decyloxy)pentanamide, the following compounds were obtained.

triinethylainmoniun iodide m.p. 91 92'C.

N- (Tridecyloxy )pentanainido ]propyl N,N,N-trimethylammoniun iodide m.p. 96 98 0

C.

N- (Tetradecyloxy )pentanamido ]ethyl}- N,N,N-trimethylammioniun iodide m.p. 93 94 0

C.

3- (Hexadecyloxy)pentananido ]propyl}- N,N,N-trinethylammioniun iodide in.P. 98 100 0

C.

3- (Octadecylkxy)pentananido ]propyl}- N, N,N-trimethylammoniun iodide .4 t(

I

F'

34 m.p. 101 1030C.

Example 3 N-3-r11--(Dodecylthio}undecanamidolpropyl}- N,N,N-trimethvlammonium bromide To a solution of 1.5 g of N-[3- (dimethylamino)propyl]-11-(dodecylthio)undecanamide obtained in Preparation Example 5 in 100 ml of ethanol was added 0.8 g of methyl bromide, followed by stirring at room temperature for 4 days. After evaporation of the solvent, recrystallization from ethanol gave 1.2 g of the title compound.

m.p. 92 94°C

'H-NMR(CDCI

3 8(ppm); 0.88 (3H, t, 1.20 1.74 (36H, 2.11 2.29 (2H, m), 2.40 2.56 (6H, 3.31 3.53 (11H, m), 3.89 4.04 (2H, 8.62 (1H, br. s) Example 4 N-Benzyl-N-43- [11-(decylthio)undecanamido]propyvl-N,N-dimethylammonium chloride A solution of 1.5 g of N-[3-(dimethylamino)propyl]-ll-(decylthio)undecanamide obtained by a similar manner to that of Preparation Example 5 and 0.5 g of benzyl chloride in 20 ml of ethanol was refluxed for 11 hours. After evaporation of the solvent, the product was recrystallized from ethanol to give 1.8 g of the title compound.

MWOMMEd r 35 m.p. 75 77WC '1-NMR(CDCl 3 B(ppm); 0.88 (3H, t, 1.16 1.70 (32H1, in), 2.13 2.32 (2H, in), 2.37 (2H1, t, J=7.8Hz), 2.49 (4H, t, J=7.3Hz), 3.19 (6H, 3.35 3.47 (211, mn), 3.85- 3.98 (2H, mn), 4.79 (2H, 7.41 7.63 mn), 8.60 (1H, br. s) Following a substantially similar reaction to that of Example 4 using propyl bromide or allyl bromide in place of benzyl chloride, the following compounds were obtained.

l1-(Decylthio)undecanamido]propyl}-N,Ndiinethyl -N-propylamnoniun bromide m.p. 70 721C.

N-Ally1 [11- (dodecylthio )undecananido] propyll}, N-diinethylainmoniun bromide m.p. 80 821C.

Example N- F11- (Dodecvlthio undecanamidol1pro-pyl l- N,NN-trinethvlamnoniun iethvlsulf te A solution of 2.0 g of N-[3-(dimethylamino)propyl (dodecylthio unde~canamide obtained in Preparation Example 5 and 0.6 g of diinethyl sulfate in ml of methanol was ref luxed for,2 hours. After evaporation of the solvent, the product was recrystal- 7 'ii 21 *1

I

p 41~

U,

36 lized from methanol to give 2.4 g of the title compound.

in.p. 90 921 3

C

1 H-NMR(CDCl 3 5(ppin); 0.88 (3H, t, 1.20 1.69 (36H, mn), 2.02 2.19 (2H, in), 2.34 (2H, t, J=7.7Hz), 2.50 (4H, t, J=7.3Hz), 3.24 (9H, 3.33 3.47 (2H, in), 3.58 3.71 (2H, in), 3.72 (3H, 8.07 (1H, br. s) Following a substantially similar reaction to that of Example 5 using triinethyl phosphate in place of dimethyl sulfate, the following compound was obtained.

N-{3-[11l-(Dodecylthio)undecanai' -]propyl.- N, N,N-tr.imethylainmoniun diinethylphosphate in.p. 65 671C.

Example 6 N,NN-triIeth1wiam~onium p-toluenesulfonate p A solution of 1.5 g of N-[3-(dimethylaino)propyl]-l-(dodecylthio vndecanamide obtained in Preparation Example 5 and 0.7 g of methyl ptoluenesulfonate in 25 ml of ethanol was ref luxed for 2 hours. After evaporation of the solvent, tha product was recrystallized from ethanol ether to give 1.6 g of the title compound.

in.p. 90 920C IH-NMR(CDCl 3 S(ppm); 0.88 (3H, t, 1.11 1.66 (36H, in), 1.98 2.26 (4H, in),

A

1 37 2.36 (3H, 2.50 (4H, t, J=7.3Hz), 3.23 (9H1, 3.29 3.43 (2H1, in), 3.67 3.81 (2H, in), 7.18 (2H1, d, J=7.9Hz), 7.72 (2H, d, J=8.lHz), 8.30 (1H, br. s) Following a substantially similar reaction to that of~ Example 6 using sulfonic acid esters and sulfuric acid esters, the following compounds were obtained.

N- [11- (Dodecylthio )undecanamido 3propyl N N-trimethylammonium methylsulfonate m.p. 88 90 0

C.

[11- (Dodecylthio )undecanamido ]propyll- N,N,N-trimethylammonium benzenesulfonate m.p. 86 89 0

C.

[11- (Dodecylthio )undecanamido ]propyl}- N,N,N-trimethylammonium ethylsulf ate M.P. 98 1000W.

3-[11- (Dodecylthio )undecanamido Jpropyl}-Nethyl-N, N-dimethylammonium ethylsulf ate mip. 52 54*C.

Example 7 N-1 3- r i- (Dodecylthio 'undecanamido ipropyll- N.N,N-trimethylanimonium nitrate

U

I 38 To a solution of 1.5 g of N-{3-[ll-(dodecylthio)undecanamido]propyl-N,N,N-trimethylammonium iodide obtained in Example 1 in 150 ml of ethanol was added a solution of 0.4 g of silver nitrate in 15 ml of water, followed by stirring at room temperature for 15 hours.

After removal of the precipitated silver iodide, the so-vent was evaporated, and the product was recrystallized from ethanol to give 0.5 g of the title compound.

m.p. 93 95 0

C

IH-NMR(CDCI

3 6(ppm); 0.88 (3H, t, 1.19 1.69 (36H, 2.00 2.17 (2H, m), 2.27 (2H, t, J=7.5Hz), 2.50 (4H, t, J=7.4Hz), 3.27 (9H, 3.30 3.43 (2H, m), 3.64 3.78 (2H, 7.78 (1H, br. s) Following a substantially similar reaction to that of Example 7 using other silver salts in place of silver nitrate, the following compounds were obtained.

N-{3-[11-(Dodecylthio)undecanamido]propyl}- N,N,N-trimethylammonium fluoride m.p. 63 65 0

C.

N-{3-[ll-(Dodecylthio)undecanamido]propyl}- N,N,N-trimethylammonium chloride m.p. 93 95 0

C.

N-{3-[11-(Dodecylthio)undecanamido]propyl}ru. .1I i l 1 S 1 i 1 39 N,N,N-trimethylammonium nitrite m.p. 94 960C.

Example 8 l1-(Dodecylthio)undecanamidolpropyl}- N,N,N-trimethylammonium acetate To a solution of 3.0 g of N-{3-[11- (dodecylthio)undecanamido]propyl}-N,N,N-trimethylammonium p-toluenesulfonate obtained in Example 6 in ml of ethanol was passed through a column packed with 100 ml of a strong basic anion exchange resin of which anion was converted into a type of acetic acid. After evaporation of the solvent, the product was recrystallized from ethanol acetone to give 0.5 g of the title compound.

m.p. 79 81 0

C

'H-NMR(CDC1,) 8(ppm); 0.88 (3H, t, 1.15-1.69 (36H, 1.95 2.11 (5H, m), 2.26 (2H, t, J=7.7Hz), 2.49 (4H, t, J=7.2Hz), 3.25 (9H, 3.31 3.42 (2H, m), 4.03 4.15 (2H, 9.28 9.39 (IH, m) (Experiment) Hair generating effect test Groups each of 5 male C3H mice, 7 weeks old, were used for a test of the hair generating effect of the alkanamidoammonium compounds. Dorsal hairs were shaved by a pair of hair clippers, and 0.2 ml of each of the samples in Table 1 was applied once a day on the 1 N v *3 i 1 40 shaved area for 10 days. The degree of hair generation was evaluated macroscopically by the following seven grades.

0 No hair generation is observed.

1 few vellus hairs grow.

2 A few terminal hairs grow.

3 Terminal hairs grow on 25% of the shaved area.

4 Terminal hairs grow on 50% of the shaved area.

Terminal hairs grow on 75% of the shaved area.

6 Terminal hairs grow on 100% of the shaved area.

42 Days after initiation of the application of the sample, results are expressed as the mean value of the evaluation and are shown in Table 2.

21 1 1 1 1 1 1 M w yr.

4 41 Table 1 Sample No. Compound A A 2% ethanol solution of N-{3-[11- (Dodecylthio )undecanamido ]propyl N,N,N-trimethylammnonium iodide B A 2% ethanol solution of (tetradecylthio )pentanamido ]propyl N, N-trimethylammoniuf iodide C A 2% ethanol solution of N-benzylll-(decylthio)undecanamido]propyll} N-dimethylammonium iodide D A 2% ethanol solution of (tetradecyloxy) pentanamido Ipropyl N, N,N-trimethylammonium iodide E A 2% ethanol solution of (hexadecyloxy) pentanamido ]propyl N,N,N-trimethylaxnmonium iodide F Ethanol G Control (no application)

I

B s~ 2, r; i if C' 42 Table 2 Sample No. Mean value of evaluation A 2.4 B 4.6 C 5.8 D 4.2 E 1.6 F 0 G 0 INDUSTRIAL UTILIZATION The compounds of the present invention have an e.xcellent hair generating effect, and therefore they are useful as hair generating agents.

1 r a

L

'TrT i E -Q1 fX Clr

Claims (4)

1. An alkanamidoammonium compound represented by the formula: O R 3 R II I R- A R 2 C N N R 7 1 -X m m [wherein R 1 is an alkyl group having 1 to 22 carbon atoms or a cycloalkyl group having 3 to 8 carbon atoms, R 2 is an alkylene group having 1 to 15 carbon atoms, R 3 is a hydrogen atom or an alkyl group having 1 to carbon atoms, R 4 is an alkylene group having 2 to carbon atoms, R 5 and R 6 which may be the same or different, are each an alkyl group having 1 to 5 carb.n atoms, R 7 is an alkyl group having 1 to 22 carbon atoms, an alkenyl group having 2 to 10 carbon atoms or an alkyl group having 1 to 5 carbon atoms substituted by a phenyl group, A is an oxygen atom or a group represented by the formula: i -S- II(0) (0)n (wherein n is an integer of 0 to X m is an anion and m is an integer corresponding to the number of electric c h: -i 44 charge of the anion for X].

2. 3- [11- (Dodecylthio )undecanamido ]propyl}- N, N,N-trimethylammonium acetate. V4 1 ~t 45 ABSTRACT Alkanamidoammonium compounds represented by the formula: 0 R 3 R II I I R -A-R 2 R N R R' 1 S-Xm- m [wherein R 1 is an alkyl group or a cycloalkyl group, R 2 is an alkylene group, R 3 is a hydrogen atom or an alkyl group, R 4 is an alkylene group, R 5 and R 6 which may be the same or different, are each an alkyl group, R 7 is an alkyl group, an alkenyl group or an alkyl group substi- tuted by a phenyl group, A is an oxygen atom or a group represented by the formula: 4 .i -S- II (0)n (wherein n is an integer of 0 to Xm- is an anion and m is an integer corresponding to the number of electric charge of the anion for X] have an excellent hair generating effect. eX T ii .'ii_ I is i r bI ,qr- I 1

9. INTERNATIONAL SEARCH REPORT International Application No PCT/JP92/01014 I. CLASSIFICATION OF SUBJECT MATTER (if several classification symbols apply, indicate all) According to International Patent Classificatlon (IPC) or to both National Classification and IPC Int. Cl 5 C07C235/10, A61K7/06, C07C317/44, C07C323/60 II. FIELDS SEARCHED Minimum Documentation Searched 7 Classlficatlon System I Classification Symbols IPC C07C235/10, A61K7/06, C07C317/44, C07C323/60 Documentation Searched other than Minimum Documentation to the Extent that such Documents are Included In the Fields Searched III. DOCUMENTS CONSIDERED TO BE RELEVANT 9 Category Citation of Document, with Indication, where appropriate, of the relevant passages 2 Relevant to Claim No. 1 A JP, A, 50-19719 (Ban Daic Co., Inc.), 1-2 March 1, 1975 (01. 03. US, A, 3855290 DE, A, 2351160 A JP, A, 54-130509 (The Procter 1-2 Gamble Co.), June 29, 1979 (29. 06. 79), (Family: none) Special categories of cited documents: 10 later document published after the International filing date or document defining the general state of the art which is not priority date and not in conflict with the application but cited to considered to be of particular relevance understand the principle or theory underlying the invention earlier document but published on or after the international document of particular relevance: the claimed invention cannot filing date be considered novel or cannot be considered to involve an iling ie nventive step document which may throw doubts On priority claim(s) or Y document of oarticular relevance: the claimed nvention cannot which i cited to etablh the publication date of nthr be considered to involve an inventive step when the document citation or other special reason (as specified) is combined with one or more other such documents, such document referring to an oral disclosure, use, exhibition or combination being obvious to a pereon skilled in the art other means document member of the sme patent family document published prior to'the international filing date but later than the priority date claimed IV. CERTIFICATION Date of the Actual Completion of the International Search Date of Mailing of this International Search Report October 28, 1992 (28. 10. 92) November 17, 1992 (17. 11. 92) International Searching Authority Signature of Authorized Officer Japanese Patent Office Form PCT/ISA/210 (second sheet) (January 1985) ii u. I ;B 1 i 1 4 i 141 wwasuaRPCT/JP 9 2 0 1 0 1 4 W O PM UIPC) I t. at'- 0 0 3 7 4 007C235/10, A61K7/06.0731/4 00 7C323/60 0070235/10. A61K7/06, C070317/44, ao 70323/60 A J P, A, 50 1 9 7 19( 9 7VF 1-2 1. 3A. 1 975 01. 0 3. 7 &US. A. 3855290&DE. A.2351160 A J PA. 54- 1359(o 1-2 FEJ EcIfi4U FPj E3~U* Erx7ij Iv.w .WiU MO*i-T L ft

28. 10. 92 17,11.92 E3 E .qr (ISA/JP) 0APCT/lSA/210oCZ 2 i) (198V-10,)