Amide derivatives, process for their manufacture and pharmaceutical or veterinary compositions containing them

Claim 2

An acylanilide of the formula:- wherein R is cyano, carbamoyl, nitro, fluoro, chloro, bromo, iodo or hydrogen, or alkyl, alkoxy, alkanoyl, alkylthio, alkylsulphinyl, alkylsulphonyl, perfluoroalkyl, perfluoroalkylthio, perfluoroalkylsulphinyl or perfluoroalkylsulphonyl each of up to 4 carbon atoms, or phenylthio, phenylsulphinyl or phenylsulphonyl; wherein R 2 is cyano, carbamoyl, nitro, fluoro, chloro, bromo or iodo, or alkanoyl, alkylthio, alkylsulphinyl, alkylsulphonyl, perfluoroalkyl, perfluoroalkylthio, perfluoroalkylsulphinyl or perfluoroalkylsulphonyl each of up to 4 carbon atoms, or phenylthio, phenylsulphinyl or phenylsulphonyl; wherein R 3 is hydrogen or alkyl of up to 4 carbon atoms, or is joined to R 5 as stated below; wherein R 4 is alkyl of 2 to 4 carbon atoms, or has the formula -CX 1 X 2 X 3 wherein X 1 , X 2 and X 3 , which may be the same or different, each is hydrogen, fluorine or chlorine; wherein R 5 is hydrogen, hydroxy or alkoxy or acyloxy each of up to 15 carbon atoms, or is joined to R to form an oxycarbonyl group such that together with the -N-CO-C- part of the molecule it forms an oxazolidinedione group; wherein R 6 is hydrogen or halogen; and wherein the benzene ring A bears one, two or three substituents selected from hydrogen, halogen, nitro, carboxy, carbamoyl and cyano, and alkyl, alkoxy, alkanoyl, alkylthio, alkylsulphinyl, alkylsulphonyl, perfluoroalkyl, perfluoroalkylthio, perfluoroalkylsulphinyl, perfluoroalkylsulphonyl, alkoxycarbonyl and N-alkylcarbamoyl each of up to 4 carbon atoms, and phenyl, phenylthio, phenylaulphinyl and phenylsulphonyl; or bears a buta-1,3-dienylene substituent which together with the benzene ring A forms a naphthelene ring.

Claim 3

An acylanilide as claimed in claim 1 wherein R 1 is cyano, carbamoyl, nitro, fluoro, chloro, bromo, iodo, hydrogen, methyl, ethyl, methoxy, ethoxy, formyl, acetyl, methylthio, ethylthio, methylsulphinyl, methylsulphonyl, trifluoromethyl, pentafluoroethyl, trifluoromethylthio, trifluoromethylsulphinyl, trifluoromethylsulphonyl, phenylthio, phenylsulphinyl or phenylsulphonyl; wherein R 2 is cyano, carbamoyl, nitro, fluoro, chloro, bromo, iodo, formyl, acetyl, methylthio, ethylthio, methylsulphinyl, methylsulphonyl, trifluoromethyl, pentafluoroethyl, trifluoromethylthio, trifluoromethylsulphinyl, trifluoromethylsulphonyl, phenylthio, phenylsulphinyl or phenylsulphonyl; wherein R 3 is hydrogen, methyl or ethyl, or is joined to R as stated below; wherein R 4 is methyl, ethyl, n-propyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl or trichloromethyl; wherein R 5 is hydrogen, hydroxy, methoxy, ethoxy, propyloxy, n-butyloxy, decyloxy, acetoxy, propionyloxy, decanoyloxy or dodecanoyloxy, or is joined to R 3 to form an oxycarbonyl group as stated in claim 1; wherein R 6 is hydrogen or chloro; and wherein the benzene ring A bears one or two substituents selected from hydrogen, fluoro, chloro, bromo, iodo, nitro, carboxy, carbamoyl, cyano, methyl, ethyl, methoxy, ethoxy, formyl, acetyl, methylthio, ethylthio, methylsulphinyl,methylsulphonyl, trifluoromethyl, pentafluoroethyl, trifluoromethylthio, trifluoromethylsulphinyl, trifluoromethylsulphonyl, methoxycarbonyl, ethoxycarbonyl, N-methylcarbamoyl, phenyl, phenylthio, phenylsulphinyl and phenylsulphonyl; or bears a 1,3-butadienylene substituent as stated in claim 1.

Claim 4

An acylanilide as claimed in claim 1 wherein R 1 is trifluoromethyl and R 2 is nitro or cyano; or R 1 is chloro and R 2 is chloro, nitro, cyano, methylthio, methylsulphinyl or methylsulphonyl; or R 1 is cyano and R 2 is chloro; or R 1 is nitro and R 2 is chloro or cyano; or R 1 is methylthio and R 2 is cyano; or R 1 is hydrogen and R 2 is methylthio; wherein R 3 is hydrogen; wherein R 4 is methyl; wherein R 5 is hydroxy; wherein R 6 is hydrogen; and wherein the benzene ring A bears one or two substituents only,one of which is a nitro, fluoro, chloro, trifluoromethyl, cyano, methoxycarbonyl, methylthio, methylsulphinyl or methanesulphonyl substituent in the para-position and the other of which is hydrogen or chloro in the meta-position.

Claim 5

Anacylanilide as claimed in claim 1 wherein R 1 and R 2 , which may be the same or different, each is cyano, nitro, trifluoromethyl or chloro, R 3 and R 6 areboth hydrogen, R 4 is methyl, R 5 is hydroxy and the ring A bears one substituent in the para-position which is a nitro, fluoro, trifluoromethyl, cyano, methoxycarbonyl, methylthio or methylsulphinyl substituent.

Claim 6

The compound 3,4-dichloro-(2-hydroxy-2-p-nitrophenylpropionyl)anilide; 4-nitro-3-trifluoromethyl-(2-hydroxy-2-p-nitrophenyl- propionyllaniline or 4-cyano-3-trifluoromethyl-(2-hydroxy-2-p-nitrophenyl- propionyl)aniline.

Claim 7

The compound 3,4-dichloro-(2-hydroxy-2-p-nitrophenylpropionyl)anilide; 4-nitro-3-trifluoromethyl-(2-hydroxy-2-p-nitrophenyl- propionyllaniline or 4-cyano-3-trifluoromethyl-(2-hydroxy-2-p-nitrophenyl- propionyl)aniline.

Claim 8

The compound 3-chloro-4-nitro-N-(2-hydroxy-2-p-nitrophenylpropionyl)aniline; 3-chloro-4-methylsulphonyl-N-(2-hydroxy-2-p-nitror- phenylpropionyl)aniline; 4-nitro-3-trifluoromethyl-N-(2-hydroxy-2-p-trifluoro- methylphenylpropionyl)aniline; 3-chloro-4-nitro-N-(2-hydroxy-2-p-trifluoromethylphenyl- propionyl)aniline; 4-nitro-3-trifluoromethyl-N-(2-p-cyanophenyl-2-hydroxy- propionyl)aniline; 4-nitro-3-trifluoromethyl-N-(2-hydroxy-2-p-hydroxyl- propionyl)aniline; 4-nitro-3-trifluoromethyl-N-(2-hydroxy-2-p-methyl- sulphonylphenylpropionyl)aniline; 3,4-dichloro-N-(2-hydroxy-2-p-methylsulphinylphenyl- propionyl)aniline; and 3,4-dichloro-N-(2-p-acetylphenyl-2-hydroxypropionyl)-aniline.

Claim 9

The compound 3-chloro-4-nitro-N-(2-hydroxy-2-p-nitrophenylpropionyl)aniline; 3-chloro-4-methylsulphonyl-N-(2-hydroxy-2-p-nitror- phenylpropionyl)aniline; 4-nitro-3-trifluoromethyl-N-(2-hydroxy-2-p-trifluoro- methylphenylpropionyl)aniline; 3-chloro-4-nitro-N-(2-hydroxy-2-p-trifluoromethylphenyl- propionyl)aniline; 4-nitro-3-trifluoromethyl-N-(2-p-cyanophenyl-2-hydroxy- propionyl)aniline; 4-nitro-3-trifluoromethyl-N-(2-hydroxy-2-p-hydroxyl- propionyl)aniline; 4-nitro-3-trifluoromethyl-N-(2-hydroxy-2-p-methyl- sulphonylphenylpropionyl)aniline; 3,4-dichloro-N-(2-hydroxy-2-p-methylsulphinylphenyl- propionyl)aniline; and 3,4-dichloro-N-(2-p-acetylphenyl-2-hydroxypropionyl)-aniline.

Claim 10

A process for the manufacture of an acylanilide, claimed in any one of claims 1 to 6, which comprises: (a) for the manufacture of an acylanilide wherein R 3 is hydrogen and R 5 is other than hydroxy, the reaction of an amine of the formula:- wherein R 1 , R 2 and R 6 have the meanings stated in any one of claims 1 to 4, with an acid of the formula: wherein R 4 and A have the meanings stated in any one of claims 1 to 4 and wherein R 5 is hydrogen or alkoxy or acyloxy as defined in claim 1 or 2, or with a reactive derivative of said acid; or (b) for the manufacture of an acylanilide wherein R 3 and R 5 are joined together to form carbonyl-oxy, that is, an oxazolidinedione, the reaction of an isocyanate of the formula wherein R 1 , R 2 and R 6 have the meanings stated above, with an ester of the formula wherein R 4 and A have the meanings stated.above and wherein R is alkyl of up to 6 carbon atoms; or (c) for the manufacture of an acylanilide wherein R 5 is hydroxy, the hydrolysis of the corresponding acylanilide wherein R 5 is acyloxy; or (d) for the manufacture of an acylanilide wherein R 3 is hydrogen and R 5 is hydroxy, the hydrolysis of the corresponding oxazolidinedione wherein R 3 and R 5 are joined together to form carbonyl-oxy; or (e) for the manufacture of an acylanilide wherein R 3 is alkyl, the alkylation of the corresponding acylanilide wherein R 3 is hydrogen; or (f) for the manufacture of an acylanilide wherein R 5 is acyloxy, the acylation of the corresponding acylanilide wherein R 5 is hydroxy; or (g) for the manufacture of an acylanilide wherein R 3 and R 5 are joined together to form carbonyl-oxy, that is, an oxazolidinedione, the reaction of the corresponding acylanilide wherein R 3 is hydrogen and R 5 is hydroxy with phosgene; or (h) for the manufacture of an acylanilide wherein R 4 is chloromethyl and R 5 is hydroxy, the reaction of an epoxide of the formula: wherein R 1 , R 2 , R 3 , R 6 and A have the meanings stated above, with hydrogen chloride; or (i) for the manufacture of an acylanilide wherein one or more of R 1 , R 2 and a substituent in the benzene ring A is alkylsulphinyl, perfluoroalkylsulphinyl or phenylsulphinyl, or is alkylsulphonyl, perfluoroalkylsulphonyl or phenylsulphonyl, the oxidation of the corresponding acylanilide wherein one or more of R 1 , R 2 anda substituent in the benzene ring A is alkylthio, perfluoroalkylthio or phenylthio, respectively; or (j) for the manufacture of an acylanilide wherein a substituent in the benzene ring A is carboxy, the oxidation of the corresponding acylanilide wherein a substituent in the benzene ring A is formyl; or (kl for the manufacture of an acylanilide wherein a substituent in the benzene ring A is alkoxycarbonyl, the esterification of the corresponding acylanilide wherein a substituent in the benzene ring A is carboxy.

Claim 11

A pharmaceutical or veterinary composition which comprises an acylanilide, claimed in any of claims 1 to 6, in association with a pharmaceutically acceptable diluent or carrier.

Claim 12

A composition as claimed in claim 8 which additionally contains one or more drugs selected from antioestrogens, progestins, inhibitors of gonadotrophin secretion, cytotoxic agents, antibiotics and anti-inflammatory agents.

Claim 14

A process for the manufacture of an acylanilide of the formula:- wherein R is cyano, carbamoyl, nitro, fluoro, chloro, bromo, iodo or hydrogen, or alkyl, alkoxy, alkanoyl, alkylthio, alkylsulphinyl, alkylsulphonyl, perfluoroalkyl, perfluoroalkylthio, perfluoroalkylsulphinyl or pcrfluoroalkylsulphonyl each of up to 4 carbon atoms, or phenylthio, phenylsulphinyl or phenylsulphonyl; wherein R 2 is cyano, carbamoyl, nitro, fluoro, chloro, bromo or iodo, or alkanoyl, .alkylthio, alkylsulphinyl, alkylsulphonyl, perfluoroalkyl, perfluoroalkylthio, perfluoroalkylsulphinyl or perfluoroalkylsulphonyl each of up to 4 carbon atoms, or phenylthio, phenylsulphinyl or phenylsulphonyl; wherein R 3 is hydrogen or alkyl of up to 4 carbon atoms, or is joined to R 5 as stated below; wherein R 4 is alkyl of 2 to 4 carbon atoms, or has the formula -CX 1 X 2 X 3 wherein X 1 , X 2 and X 3 , which may be the. same or different, each is hydrogen, fluorine or chlorine; wherein R 5 is hydrogen, hydroxy or alkoxy or acyloxy each of up to 15 carbon atoms, or is joined to R 3 to 'form an oxycarbonyl group such that together with the -N-CO-C-part of the molecule it forms an oxazolidinedione group; wherein R 6 is hydrogen or halogen; and wherein the benzene ring A bears one, two or three substituents selected from hydrogen, halogen, nitro, carboxy, carbamoyl and cyano, and alkyl, alkoxy, alkanoyl, alkylthio, alkylsulphinyl, alkylsulphonyl, perfluoroalkyl, perfluoroalkylthio, perfluoroalkylsulphinyl, perfluoroalkylsulphonyl, alkoxycarbonyl and N-alkylcarbamoyl each of up to 4 carbon atoms, and phenyl, phenylthio, phenylsulphinyl and'phenylsulphonyl; or bears a buta-1,3-dienylene substituent which together with the benzene ring A forms a naphthalene ring, characterised by either:- (a) for the manufacture of an acylanilide wherein R 3 is hydrogen and R 5 is other than hydroxy, the reaction of an amine of the formula:- wherein R 1 , R 2 and R 6 have the meanings stated above, with an acid of the formula:- wherein R 4 and A have the meanings stated above and wherein R 5 is hydrogen or alkoxy or acyloxy as defined above, or with a reactive derivative of said acid; or (b) for the manufacture of an acylanilide wherein R 3 and R 5 are joined together to form carbonyl-oxy, that is, an oxazolidinedione, the reaction of an isocyanate of the formula wherein R 1 , R2and R 6 have the meanings stated above, with an ester of the formula wherein R 4 and A have the meanings stated above and wherein R is alkyl of up to 6 carbon atoms; or (c) for the manufacture of an acylanilide wherein R 5 is hydroxy.,.the hydrolysis of the corresponding acylanilide wherein R 5 is acyloxy; or (d) for the manufacture of an acylanilide wherein R 3 is hydrogen and R 5 is hydroxy, the hydrolysis of the corresponding oxazolidinedione wherein R 3 and R 5 are joined together to form carbonyl-oxy; or (e) for the manufacture of an acylanilide wherein R 3 is alkyl, the alkylation of the corresponding acylanilide wherein R 3 is hydrogen; or (f) for the manufacture of an acylanilide wherein R 5 is acyloxy, the acylation of the corresponding acylanilide wherein R 5 is hydroxy; or (g) for the manufacture of an acylanilide wherein R 3 and R 5 are joined together to form carbonyl-oxy, that is, an oxazolidinedione, the reaction of the corresponding acylanilide wherein R 3 is hydrogen and R 5 is hydroxy with phosgene; or (h)_ .for the manufacture of an acylanilide wherein R 4 is chloromethyl and R 5 is hydroxy, the reaction of an epoxide of the formula: wherein R 1 , R 2 , R 3 , R 6 and A have the meanings stated above, with hydrogen chloride; or (i) for the manufacture of an acylanilide wherein one or more of R l , R 2 and a substituent in the benzene ring A is alkylsulphinyl, perfluoroalkylsulphinyl or phenylsulphinyl, or is alkylsulphonyl, perfluoroalkylsulphonyl or phenylsulphonyl, the oxidation of the corresponding acylanilide wherein one or more of R l , R 2 and a substituent in the benzene ring A is alkylthio, perfluoroalkylthio or phenylthio, respectively; or (j) for the manufacture of an acylanilide wherein a substituent in the benzene ring A is carboxy, the oxidation of the corresponding acylanilide wherein a substituent in the benzene ring A is formyl; or (k) for the manufacture of an acylanilide wherein a substituent in the benzene ring A is alkoxycarbonyl, the esterification of the corresponding acylanilide wherein a substituent in the benzene ring A is carboxy.

Claim 15

A process for the manufacture of an acylanilide of the formula:- wherein R is cyano, carbamoyl, nitro, fluoro, chloro, bromo, iodo or hydrogen, or alkyl, alkoxy, alkanoyl, alkylthio, alkylsulphinyl, alkylsulphonyl, perfluoroalkyl, perfluoroalkylthio, perfluoroalkylsulphinyl or pcrfluoroalkylsulphonyl each of up to 4 carbon atoms, or phenylthio, phenylsulphinyl or phenylsulphonyl; wherein R 2 is cyano, carbamoyl, nitro, fluoro, chloro, bromo or iodo, or alkanoyl, .alkylthio, alkylsulphinyl, alkylsulphonyl, perfluoroalkyl, perfluoroalkylthio, perfluoroalkylsulphinyl or perfluoroalkylsulphonyl each of up to 4 carbon atoms, or phenylthio, phenylsulphinyl or phenylsulphonyl; wherein R 3 is hydrogen or alkyl of up to 4 carbon atoms, or is joined to R 5 as stated below; wherein R 4 is alkyl of 2 to 4 carbon atoms, or has the formula -CX 1 X 2 X 3 wherein X 1 , X 2 and X 3 , which may be the. same or different, each is hydrogen, fluorine or chlorine; wherein R 5 is hydrogen, hydroxy or alkoxy or acyloxy each of up to 15 carbon atoms, or is joined to R 3 to 'form an oxycarbonyl group such that together with the -N-CO-C-part of the molecule it forms an oxazolidinedione group; wherein R 6 is hydrogen or halogen; and wherein the benzene ring A bears one, two or three substituents selected from hydrogen, halogen, nitro, carboxy, carbamoyl and cyano, and alkyl, alkoxy, alkanoyl, alkylthio, alkylsulphinyl, alkylsulphonyl, perfluoroalkyl, perfluoroalkylthio, perfluoroalkylsulphinyl, perfluoroalkylsulphonyl, alkoxycarbonyl and N-alkylcarbamoyl each of up to 4 carbon atoms, and phenyl, phenylthio, phenylsulphinyl and'phenylsulphonyl; or bears a buta-1,3-dienylene substituent which together with the benzene ring A forms a naphthalene ring, characterised by either:- (a) for the manufacture of an acylanilide wherein R 3 is hydrogen and R 5 is other than hydroxy, the reaction of an amine of the formula:- wherein R 1 , R 2 and R 6 have the meanings stated above, with an acid of the formula:- wherein R 4 and A have the meanings stated above and wherein R 5 is hydrogen or alkoxy or acyloxy as defined above, or with a reactive derivative of said acid; or (b) for the manufacture of an acylanilide wherein R 3 and R 5 are joined together to form carbonyl-oxy, that is, an oxazolidinedione, the reaction of an isocyanate of the formula wherein R 1 , R2and R 6 have the meanings stated above, with an ester of the formula wherein R 4 and A have the meanings stated above and wherein R is alkyl of up to 6 carbon atoms; or (c) for the manufacture of an acylanilide wherein R 5 is hydroxy.,.the hydrolysis of the corresponding acylanilide wherein R 5 is acyloxy; or (d) for the manufacture of an acylanilide wherein R 3 is hydrogen and R 5 is hydroxy, the hydrolysis of the corresponding oxazolidinedione wherein R 3 and R 5 are joined together to form carbonyl-oxy; or (e) for the manufacture of an acylanilide wherein R 3 is alkyl, the alkylation of the corresponding acylanilide wherein R 3 is hydrogen; or (f) for the manufacture of an acylanilide wherein R 5 is acyloxy, the acylation of the corresponding acylanilide wherein R 5 is hydroxy; or (g) for the manufacture of an acylanilide wherein R 3 and R 5 are joined together to form carbonyl-oxy, that is, an oxazolidinedione, the reaction of the corresponding acylanilide wherein R 3 is hydrogen and R 5 is hydroxy with phosgene; or (h)_ .for the manufacture of an acylanilide wherein R 4 is chloromethyl and R 5 is hydroxy, the reaction of an epoxide of the formula: wherein R 1 , R 2 , R 3 , R 6 and A have the meanings stated above, with hydrogen chloride; or (i) for the manufacture of an acylanilide wherein one or more of R l , R 2 and a substituent in the benzene ring A is alkylsulphinyl, perfluoroalkylsulphinyl or phenylsulphinyl, or is alkylsulphonyl, perfluoroalkylsulphonyl or phenylsulphonyl, the oxidation of the corresponding acylanilide wherein one or more of R l , R 2 and a substituent in the benzene ring A is alkylthio, perfluoroalkylthio or phenylthio, respectively; or (j) for the manufacture of an acylanilide wherein a substituent in the benzene ring A is carboxy, the oxidation of the corresponding acylanilide wherein a substituent in the benzene ring A is formyl; or (k) for the manufacture of an acylanilide wherein a substituent in the benzene ring A is alkoxycarbonyl, the esterification of the corresponding acylanilide wherein a substituent in the benzene ring A is carboxy.

Claim 16

A process for the manufacture of an acylanilide of the formula:- wherein R 1 is trifluoromethyl and R 2 is nitro or cyano; or R 1 is chloro and R 2 is chloro, nitro, cyano, methylthio, methylsulphinyl or methylsulphonyl; or R 1 is cyano and R 2 is chloro; or R 1 is nitro and R 2 is chloro or cyano; or R 1 is methylthio and R 2 is cyano; or R 1 is hydrogen and R 2 is methylthio.; and wherein the benzene ring A bears one or two substituents only, one of which is a nitro, fluoro, chloro, trifluoromethyl, cyano, methoxycarbonyl, methylthio, methylsulphinyl or methanesulphonyl substituent in the para-position and the other of which is hydrogen or chloro in the meta-position, characterised by the reaction of an amine of the formula:- wherein R 1 and R 2 have the meanings stated above, with an acid of the formula: wherein A has the meaning stated above and wherein "Acyl" is acyl of up to 15 carbon atoms, or with a reactive derivative of said acid; followed by the hydrolysis of the O-Acyl group to the -OH group.

Claim 17

A process for the manufacture of an acylanilide of the formula:- wherein R 1 is trifluoromethyl and R 2 is nitro or cyano; or R 1 is chloro and R 2 is chloro, nitro, cyano, methylthio, methylsulphinyl or methylsulphonyl; or R 1 is cyano and R 2 is chloro; or R 1 is nitro and R 2 is chloro or cyano; or R 1 is methylthio and R 2 is cyano; or R 1 is hydrogen and R 2 is methylthio.; and wherein the benzene ring A bears one or two substituents only, one of which is a nitro, fluoro, chloro, trifluoromethyl, cyano, methoxycarbonyl, methylthio, methylsulphinyl or methanesulphonyl substituent in the para-position and the other of which is hydrogen or chloro in the meta-position, characterised by the reaction of an amine of the formula:- wherein R 1 and R 2 have the meanings stated above, with an acid of the formula: wherein A has the meaning stated above and wherein "Acyl" is acyl of up to 15 carbon atoms, or with a reactive derivative of said acid; followed by the hydrolysis of the O-Acyl group to the -OH group.

Claim 18

A process for the manufacture of an acylanilide of the formula: wherein R 1 and R 2 , which may be the same or different each is cyano, nitro, trifluoromethyl or chloro, and the ring A bears one substituent in the para-position which is a nitro, fluoro, trifluoromethyl, cyano, methoxycarbonyl, methylthio or methylsulphinyl substituent, characterised by the reaction of an amine of the formula wherein R 1 and R 2 have the meanings stated above, with an acid of the formula:- wherein A has the meaning stated above and wherein "Acyl" is acyl of up to 15 carbon atoms, or with a reactive derivative of said acid, followed by the hydrolysis of the O-Acyl group to the -OH group.

Claim 19

A process for the manufacture of an acylanilide of the formula: wherein R 1 and R 2 , which may be the same or different each is cyano, nitro, trifluoromethyl or chloro, and the ring A bears one substituent in the para-position which is a nitro, fluoro, trifluoromethyl, cyano, methoxycarbonyl, methylthio or methylsulphinyl substituent, characterised by the reaction of an amine of the formula wherein R 1 and R 2 have the meanings stated above, with an acid of the formula:- wherein A has the meaning stated above and wherein "Acyl" is acyl of up to 15 carbon atoms, or with a reactive derivative of said acid, followed by the hydrolysis of the O-Acyl group to the -OH group.