GB2023586A

GB2023586A - Novel taurine derivatives

Info

Publication number: GB2023586A
Application number: GB7920953A
Authority: GB
Original assignee: Laboratorio Chimico Farmaceutico Causyth SpA
Current assignee: Laboratorio Chimico Farmaceutico Causyth SpA
Priority date: 1978-06-15
Filing date: 1979-06-15
Publication date: 1980-01-03
Also published as: FR2511365A1; DE2901046B2; JPS554381A; FR2465717A1; DE2901046C3; JPS6133171A; GB2023586B; FR2511365B1; IT7824587A0; ES482484A1; NL7904644A; JPS5943942B2; DE2901046A1; ES476812A1; ES482483A1; IT1096662B; BE876969A; LU81379A1

Abstract

Novel taurine derivatives of general formula (I> <IMAGE> (wherein R<1> is nicotinoyl, 3,4,5- trimethoxybenzoyl or acetylsalicyloyl and R<2> is R<1> or -CH2CH2OR<1>) have antilipemic and choleretic activities, and are made by acylation methods.

Description

SPECIFICATION Novel taurine derivatives The present invention relates to taurine derivatives. More particularly it relates to taurine derivatives which have antilipemic and choleretic activities, to processes for the preparation of such derivatives, and to pharmaceutical compositions of such derivatives.

Ta urine, otherwise known as 2-aminoethanesulphonic acid, is a naturally occurring compound of the formula (X).

In particular, it occurs in the human body as a conjugate with bile acids, the conjugate with cholic acid being taurocholic acid.

The present invention provides taurine derivatives of the general formula (I)

(wherein R1 is a nicotinoyl, 3,4,5-trimethoxybenzoyl or acetylsalicyloyl group, and R2 is as defined for R1 or is a -CH2CH2OR1 group wherein R is as defined) and pharmaceutically acceptable salts thereof.

The present taurine derivatives have various pharmacological utilities, especially antilipemic and choieretic activities.

Accordingly the present invention provides pharmaceutical compositions which contain a taurine derivative of general formula (I), or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier or diluent. The carrier or diluent can be conventional and the composition may contain further components if desired.

PHARMACOLOGICAL ACTIVITY The pharmacological activity of the present derivatives is illustrated by the following results for typical derivatives of the invention.

A) N-nicotinoyl-N-(2-nicotinoyloxy) ethyltaurine, Compound A Toxicology Mice of either sex were treated orally for 180 days with 200 mg/kg of compound A. There was no mortality nor any significant variation in the weight increase curve when compared with control mice.

Vasodilative activity The vasodilatory activity of the Compound A of the invention was investigated in comparison with (i) a mixture of the components of Compound A, i.e. N-hydroxyethyltaurine plus nicotinic acid, (ii) nicotinic acid, (iii) mesoinosital hexanicotinate (inositol niacinate), and (iv) 3-pyridylcarbinol tartrate The vasodilative activity was evaluated by administering the products endoperitoneally at the doses indicated in Table I. The test was as described for the vasodilation of the ocular conjunbtiva in guinea pigs (J. Pharmacol. 21, 192-1969).

Each value in Table 1 is the average of 10 measurements.

TABLE 1 Vasodi I ator Activity

Effect Positive Time of Dose response appearance Duration Compound (mg/kg) (o/o) (seconds) (minutes) A 0.1 0 0 0 1.0 80 90 120 10.0 100 96 120 N-hydroxyethyl taurine + nicotinic acid 10.0 0 0 0 Nicotinic acid 10.0 . 0 0 25.0 20 - 50.0 80 180 87 Mesoinosital hexanicotinate 1.0 0 0 0 10.0 100 81 87 3-pyridyl- 0.1 0 0 0 carbinol tartrate 1.0 40 - 10.0 1 100 57 120 The results show that the Compound A of the invention possesses a better activity than the 3pyridylcarbinol compound, both in terms of the number of responses and in terms of the duration. It should be noted that the mixture of N-hydroxyethyltaurine and nicotinic acid possesses no activity, thus showing different pharmacokinetics.

Choleretic activity The activity of the Compound A of the invention was evaluated in comparison with the activity of (i) N-hydroxyethyltaurine, (ii) nicotinic acid, (iii) a mixture of these two compounds (i) and (ii), and (iv) a (1-hydroxy-4-phenylcyclohexyl)butyric acid (fencibutirol), which is a known hepatoprotector.

Rats were fitted with a cannula, the bile volume was measured after the first hour, they were then treated with a test compound and the bile volume was measured after the second hour, so as to determine the percentage change. The various compounds were administered intravenously at a dose of 100 mg/kg.

The results are shown in Table 2.

TABLE 2 Chol ereti c Activity

Bile volume ml/h Dry residue mg/h after after Change after after Change Compound 1 h 2 h % 1 h 2 h A 0.75 1.14 +52.0 25.7 35.3 +40.0 N-hydroxy ethyltaurine 0.82 0.72 -12.2 29.1 26.0 -1 0.9 Nicotinic acid 0.57 0.54 4.3 21.7 20.6 -5.7 N-hydroxyethyl taurine + nicotinic aeld 0.83 0.88 +6.0 30.0 29.1 9.2 a-( 1-hydroxy- 4-phenylcyclo- hexyl)butyric acid 0.60 1.14 +90.0 23.5 32.7 +39.1 Table 2 emphasises the appearance of choleretic activity of the compound A of this invention, this activity being practically absent in the individual components and in the simple mixture when administered at the same doses.

In comparison with a-(1 -hydtoxy4-phenylcyclohexyl)butyric acid there is a smaller increase In bile volume but an equal increase in the dry residue, which suggests that the product is not hydrocholeretic but truly choleretic.

Again, the pharmacokinetics of the Compound A of the invention are different from those of the components.

Protection against hepatic intoxication by CCI4 and cold Oral administration of 5 ml/kg of a 20% solution of CCl4 in oil was followed by exposure for 5 hours to a temperature of 40C. 500 mg/kg of the Compound A of the invention were administered simultaneously with the CCl4. The BSF was tested in the blood. An average of 20 animals were used per group, and relative to the controls there was a reduction of 16%.

Antilipemic action Wistar rats were treated for 50 days with a Morris diet or a Handler diet. Simultaneously with the diet they received 200 my'keg of Compound A or of choline orally every day. The controls only received the diet. The following were examined at the end of the treatment: a) total cholesterol, total lipids and beta-lipoproteins in the serum, b) BSF excretion in the bile.

The results indicated in Table 3 are expressed as a percentage change with respect to the controls, each value being the average for 10 animals.

TABLE 3 Antilipemic Action

Morris diet Handler diet Compound Compound Parameter 1 A Choline A Choline a) Serum Total cholesterol -14.3 -22.9 -26.9 -211 Total lipids -17.0 +2,3 -19.6 +44,2 Beta-lipoproteins -34,3 +89.8 -28.9 - b) Bile BSF +23,5 -2.8 +36e0 -39.5 The antilipemic action with the diets used is apparent, thus indicating interalia a good oral absorption.

Pharmacokinetics It is possible to make reliable deductions from the pharmacological tests.

1) The tests under the diets show that the Compound A is absorbed orally, as it acts both on the lipid fractions of the serum and on the BSF bile excretion.

2) The choleretic activity after intravenous administration shows a clear difference between the activity of the Compound A and the activity of the individual components, and of the simple mixture of these in the stoichiometric proportions in which they exist in the Compound A.

Neither the components nor the mixture have any choleretic action, whereas it appears clearly in the product. It is apparent that if the product had hydroiysed immediately into its components, such activity would have been zero.

This enables it to be stated that if fission were to take place, it would take place at a level such as to modify the pharmacological profile.

3) The vasodilative action on endoperitoneal administration sh-ows a distinct difference between the Compound A and nicotinic acid.

a) At 10 mg/kg Compound A gives 100% positive response, whereas nicotinic acid gives 0% at 10 mg/kg and 80% only at 50 mg/kg.

b) The appearance time is also different Nicotinic acid has an appearance time which is double that for Compound A.

c) The duration of activity is also different. Compound A has a duration of 120 minutes at 1 mg/kg, nicotinic acid 87 minutes at 50 mg/kg.

It is apparent that if the activity of Compound A had been due to the immediate liberation of nicotinic acid, these differences could not have been observed.

It can therefore be concluded that the behaviour of Compound A of the invention differs distinctly from the behaviour of the components, for the different administration paths.

B) N,N-di-[2-(3,4,5-trimethoxybenzoyloxy)ethyl]taurine (Compound B) Toxicology Mice of either sex were treated orally for 180 days with 200 mg/kg of Compound B. No mortality occurred, nor any significant changes in the weight increase curve in comparison with the controls.

Protection against hepatic intoxication by CC14 and cold Oral administration of 5 ml/kg of a 20% solution of CC14 in oil, with simuitaneous endoperitoneal administration of 500 mg/kg of Compound B, was followed by exposure for 5 hours at 4"C. BSF in the blood (50 mg/kg i.v.) was tested. A comparison product, homocysteinethiolactone (OCT) was employed.

10 animals were treated per group, and the results expressed as percentage change with respect to the controls were as shown in Table 4.

TABLE 4 Hepatic intoxication protection

Test Number Compound Protection 1 A -27.5 OCT -22.7 2 A -17.0 OCT -18.5 BSF bile excretion Endoperitoneal administration to rats of 100 mglkg of Compound B for 4 days was followed on the fourth day, one hour after the last administration, with the rats receiving 10 ml/kg orally of a 109/0 solution of CCl4 in oil. BSF (5 mg/kg) in the bile was tested.

10 animals were used per group, and the results expressed as percentage of excretion are shown in Table 5.

TABLE 5 BSF bile excretion

Excretion Animal Group 30 min 60 min Control 56.6 66.0 CCL4 33.1 43.9 CCl4+cpdA 44.1 50.9 Curative effect on intoxication by CCI4 Oral administration to rats of 10 ml/kg of a 10% solution of CCI4 in oil was followed with endoperitoneal administration of 100 mg/kg of Compound B after 1 hour. BSF (50 mg/kg i.v.) in the blood was tested after 4 hours. 5 animals were used per group, and expressed as percentage change with respect to the control, the Compound B gave a reduction of -34.2.

Intoxication by CCI4 and curative treatment On the first day there was oral administration of 10 ml/kg of a 10% solution of CCI4 in oil and simultaneous endoperitoneal administration of 100 mg/kg of Compound B. On the second and third days, there was endoperitoneal administration of 100 mg/kg of Compound B, then testing of BSF (50 mg/kg i.v.) in the blood.

5 animals were used per group, and expressed as percentage variation with respect to the control, there was a reduction by Compound B of 16.1.

Antilipemic action Wistar rats were treated for 45 days with a Morris diet, a Handler diet or a Nath diet.

Simultaneously with the diet they received each day 200 rnkg of Compound B or choline (except for the Nath diet) orally. The controls received only the diet. 10 animals were used per group, and the results expressed as a percentage change with respect to the control are shown in Table 6.

TABLE 6 CCl4 intoxication cure

Handler diet Nath diet Morris diet Compound Compound Compound Compound Parameter B B Choline ; B B Choline a) Serum Total cholesterol -7.3 -21.1 45.2 -23.2 -22.9 Total lipids -15.9 +9.1 +44.2 -20.6 -224 +2.3 Beta lipoproteins - - - -29.7 -23.7 +89.8 b) Liver Total lipids 37.7 -29.1 -29.2 -23.4 -11.5 +14.0 Fresh organic weight -24.9 -13.3 - - - - c) Bile BSF - +23.4 39.5 - +23.8 -2.8 The antilipemic action with the diets used is apparent, indicating inter alia a good oral absorption.

Pharmacokinetics Deductions can be made from the pharmacological tests.

The tests conducted with the various types of diet, administering Compound B of the invention orally, show an evident action on the parameters considered, which obviously suggests good oral absorption. This might be an optimum by administering the compound in powder form with the diet as in the experiments, or possibly it could be improved by administration in solution.

PREPARATION OF THE TAURINE DERIVATIVES The invention also provides processes for preparing taurine derivatives of formula (I) and their salts.

One of these processes consists in treating monoethanoltaurine (II) or diethanoltaurine (III) with an activated derivative (IV) (e.g. halide, ester, mixed anhydride) of nicotinic, 3,4,5-trimethoxybenzoic or acetylsalicylic acid, in accordance with the following reaction scheme:

where R' is as defined, whereas X represents the activating residue, e.g. a halogen atom (normally chlorine), an alkoxy residue (methoxy, ethoxy), or an alkoxycarbonyloxy residue (normally a OCOOC2H5 residue).

Such reactions according to the invention can be carried out under the conditions generally adopted for the acylation of compounds of alcoholic and/or amino character. Thus, in the most frequent case in which X represents a chlorine atom, acylation is carried out in the presence of a tertiary base, such as triethylamine or pyridine.

According to a further preparative process, a compound of formula (V) is reacted with the hydrochloride (or another salt) of a ,B-acyloxyethylamine of general formula (VI), in the presence of an acid acceptor, such as sodium ethoxide. The intermediate (VII) thus obtained can then be acylated e.g.

under nitrogen with an activated derivative (IV). Likewise, compounds of formula (V) can be reacted with a hydrochloride (or another salt) of a di-(P-acyloxy)ethylamine (VEIL) in the presence of an acid acceptor, for example sodium ethoxide. The process is illustrated by the following reaction scheme:

wherein R1 and X are as previously defined, Y is a leaving group, for example chlorine, bromine, O-tosyl etc, Z is an anion, usually chloride, and M is a cation, usually sodium.

The taurine derivatives of general formula (I) can also be obtained by reacting the sodium or other salt of taurine with a compound of general formula (IX), in accordance with the scheme:

where R', X, Y and M are as previously defined.

The salts such as the compounds of formula (c) or (Id) can readily be converted by conventional methods to the corresponding acid, i.e. a taurine derivative of general formula (I). Equally the acids can be converted to salts if so desired.

EXAMPLES The present invention is further illustrated by the following non-limiting examples.

EXAMPLE 1 N-nicotinoyl-N-(2-nicotinoyloxy)ethyltaurine a) N-(2-hydroxy)ethyltaurine A solution in 2 litres of water of 31 5g of sodium bromoethanesulphonate (Organic Synthesis, Coll.

Vol. II, p. 558) and 4509 of ethanolamine was heated to 60-700C for 30 minutes. Excess ethanolamine and water were then distilled off under vacuum, and the residue dissolved in 250-270 ml of water. 2.2 litres of concentrated hydrochloric acid was added and the solution kept in a refrigerator for 1 5-20 hours. The precipitated sodium chloride was filtered off using a filter pump, and the solution concentrated until a viscous oil was obtained. The oil was diluted with 60 ml of water and ethanol (about 500 ml) then added to precipitate the reaction product. After the mixture has been left one night in a refrigerator, precipitation was almost complete. The product obtained was filtered off with a filter pump.About 130-140 g of crystalline product was obtained, having a melting point of 180-1830C.

Elementary analysis for C4H1 1O4NS: calculated %: C = 28.40; H = 6.60 found %: C = 28.70; H = 6.70.

b) N-nicotinoyl-N-(2-nicotinoyloxy)ethyltau rine 35g of N-(2-hydroxy)ethyl taurine obtained as above was placed in 100ml of pyridine. 75g of finely powdered nicotinoyl chloride hydrochloride was then slowly added under agitation. The temperature rose spontaneously, but was not allowed to exceed 80-850C. When the temperature began to fall, the solution was heated for one hour at 80--850C, and then cooled. The viscous solution was diluted with 100ml of ethanol, adjusted to a pH of 3.5 by adding concentrated hydrochloric acid, a further 500 ml of ethanol added and the solution then left to stand in a refrigerator. The required product was filtered off with a filter pump after 24 hours.About 50g of N-nicotinoyl-N-(2nicotinoyloxy)ethyl taurine was obtained, having a melting point of 175-1 760 C. The product was purified by dissolving in a minimum quantity of water and reprecipitating with ethanol.

Elementary analysis for C,6H,708N3S: calculated %: C = 50.65; H =4.52 found %: C = 50.82; H = 4.48 Infrared spectroscopy and nuclear magnetic resonance date further confirmed the identity of the product obtained.

EXAMPLE 2 N,N-di [2-(3,4,5-trimethoxybenzoyloxy) ethyl]taurine a) N,N-di-[(2-hydroxy)ethyl]taurine A solution of 90g of sodium bromoethanesulphonate (Organic Synthesis, Coll. Vol. II, p.558) and 11 0g of ethanolamine in 1 500 ml of water was heated over a steam bath for about 2 hours and the reaction mixture left to stand for one night. The excess diethanolamine and water were then distilled off under vacuum, and the residue taken up in 100ml of water and 800ml of concentrated hydrochloric acid. The solution was cooled and filtered from the sodium chloride by a filter pump. It was then concentrated under vacuum until an oil was obtained which was taken up in boiling ethanol.On cooling, a crystalline product was obtained having a melting point of 1 63-1 650C, which was recrystallised from ethanol and water. 1 6g of product were obtained, the analytical and spectroscopic data of which confirmed the identity of the product as the compound (III).

b) N,N-di-[2-(3,4,5-trimethoxybenzoyloxy) ethyl]taurine 8.5 g of product obtained in Example 2 a) was suspended in 25ml of anhydrous pyridine, and 18.4 g of 3,4,5-trimethoxybenzoyl chloride added slowly under agitation. After being left for one hour at ambient temperature, the mixture was heated to 800C for a further hour. It was then cooled to ambient temperature, diluted with 50ml of ethanol and left to stand in a refrigerator. A colourless crystalline compound precipitated which melted at 17F178 C. After recrystallisation from methanol, the melting point was 180-1 830 C. The yield was 11 .5g of pure product.

Elementary analysis for C23H350,3NS: calculated %: C = 51.91; H = 5.82; N = 2.32 found %: C = 52.07; H = 5.88; N = 2.26.

EXAMPLE 3 N-nicotinoyl-N-(2-nicotinoyloxy)ethyltaurine A solution of 2209 of the sodium salt of taurine, 90g of barium hydroxide and 70 g of ethylene oxide in 900ml of water was kept for 96 hours at 1 OOC, after which all the barium was precipitated with H2SO4 and filtered off. The solution was concentrated under reduced pressure to about 200ml and 1.8 litres of concentrated hydrochloric acid added, the precipitated sodium chloride filtered off, and the solution evaporated under reduced pressure until it was of syrupy consistency. By adding ethyl alcohol a precipitate was obtained having a melting point of 180-1 830C and whose analysis and spectra were identical with those of the product obtained in Example 1 a).

By treating this product as described in Example 1 b), N-nicotinoyl-N-(2-nicotinoyloxy)ethyltaurine was obtained, having a m.p. of 175-1 760C and whose analysis and spectra were identical with those of the product obtained in Example 1 b).

EXAMPLE 4 N,N-di-[2-(3,4,5-trim ethoxybenzoyloxy)ethyl]taurine A solution of 129 of the sodium salt of taurine, 1 0g of barium hydroxide and 8g of ethylene oxide in 100ml of was were kept for 96 hours at 1 OOC, after which barium was precipitated with H2SO4 and filtered off. The solution was concentrated under reduced pressure to about 50ml, about 1 litre of concentrated hydrochloric acid was added, the precipitate formed was filtered off and the solution evaporated under reduced pressure to a syrupy consistency. It was taken up in boiling ethanol, cooled and the precipitate obtained was filtered off and recrystallised from 80% ethanol, to give a product of m.p. 1 63-1 650C identical with the product obtained in Example 2 a).

By treating this product as described in Example 2 b), N,N-di-[2-(3,4,5trimethoxybenzoyloxy)ethyl]taurine was obtained, m.p. 178-1 820C, identical with that obtained in Example 2 b).

EXAMPLE 5 N-(nicotinoyl)-N-(2-nicotinoyloxy)ethyltau rine A mixture of 989 of cholamine hydrochloride, 2 litres of dimethoxyethane and 1 809 of nicotinoyl chloride hydrochloride was left at ambient temperature for one night under agitation. The excess HCI was removed with a current of nitrogen, the solution then evaporated at reduced pressure and redissolved in 3 litres of anhydrous ethyl alcohol. 1 40g of sodium ethoxide in 1 litre of absolute alcohol, followed by 2109 of sodium bromoethanesulphonate, was then added. 1 70g of Kl were then added and the mixture left at ambient temperature for 120h.

The resultant mixture was evaporated under reduced pressure, 750ml of pyridine added, and then 1 809 of nicotinoyl chloride hydrochloride, this latter slowly under agitation, while cooling the mass so that the temperature did not exceed 800C. It was heated for 1.5 hours, then cooled, diluted with 0.5 litres of ethanol, acidified with concentrated HCI to a pH of 3.5, and a further 2.5 litres of ethanol then added. The product, which had a m.p. of 1 71 760C, was filtered off, and was identical to the Nnicotinoyl-N-(2-nicotinoyloxy)ethyltaurine obtained in Example 1.

EXAMPLE 6 N,N-di-[2-(3,4,5-trim ethoxybenzoyloxy)ethyl]tau rine A mixture of 1 4g of diethanolamine hydrochloride, 200 ml of dimethoxyethane and 47g of 3,4,5trimethoxybenzoyl chloride was left at ambient temperature for one night under agitation. The excess HCI was removed with a current of nitrogen, and the solution then evaporated under reduced pressure and taken up in 300ml of an hydros ethyl alcohol. 14g of sodium ethoxide in 200ml of absolute alcohol was added under cooling, then 219 of sodium bromoethanesulphonate and 1 .7g of potassium iodide.

After 120 hours at ambient temperature, the inorganic salts were filtered off and the solution concentrated under reduced pressure to a small volume.

The mixture was then left to stand for one night, then filtered and crystallised from methanol. The product had a melting point of 179-1 820C and was identical to that obtained in Example 2.

EXAMPLE 7 N-(nicotinoyl)-N-(2-nicotinoyloxy)ethyltaurine 180g of nicotinoyl chloride hydrochloride was added in small portions at a temperature of OOC to 449 of ethylene oxide in 200ml of carbon tetrachloride. The mixture was left under agitation for 6 hours, after which the solvent was evaporated at reduced pressure, and the solution taken up in 1 litre of dimethoxyethane.150g of the sodium salt of taurine and 1 .5g of potassium iodide were added, after which the mixture was left under agitation for 96 hours at ambient temperature. The mixture was then evaporated under reduced pressure, 750ml of pyridine added slowly under agitation, followed by 1809 of nicotinoyl chloride hydrochloride in small portions.The mixture was heated to 800C for 2 hours, cooled, 0.5 litres of ethanol added, the mixture acidified with concentrated HCI to a pH of 3.5 and a further 2.5 litres of ethanol then added. After some hours of standing, the precipitated product was filtered off. The product had a m.p. of 175-1 760C, and was identical with the product obtained in Example 1.

EXAMPLE 8 N,N-di-[2-(3,4,5-trimethoxybenzoyloxy)ethyl]taurine 180g of nicotinoyl chloride hydrochloride was added in small portions at a temperature of OOC to 44g of ethylene oxide in 200ml of carbon tetrachloride. The mixture was left under agitation for 6 hours, after which the solvent was evaporated at reduced pressure, and the solution taken up in 1 litre of dimethoxyethane. 75g of the sodium salt of taurine and 1.5g of potassium iodide were added, after which the mixture was left under agitation at ambient temperature for 120 hours and then evaporated under reduced pressure. 1 00mI of pyridine were added, the mixture diluted with 300ml of ethanol and the solid obtained was filtered off. By recrystallising from methanol, the product was obtained having a m.p. of 1 791820 C, being identical to that obtained in Example 2.

Claims

1. A taurine derivative of the general formula (I):

wherein R1 is a nicotinoyl, 3,4,5-trimethoxybenzoyl or acetylsalicyloyl group and R2 is a group R1 as defined or -CH2CH20R1 wherein R1 is as defined; and pharmaceutically acceptable salts thereof.

2. N-nicotinoyl-N-(2-nicotinoyloxy)ethyltaurine.

3. N,N-di-[2-(3,4,5-trimethoxybenzoyloxy)ethyl]taurine.

4. A pharmaceutical composition with antilipemic and/or choleretic activity, said composition containing an effective amount of a taurine derivative of the general formula (I) or a salt thereof, as defined in Claim 1, together with a pharmaceutically acceptable carrier or diluent.

5. A process for preparing a taurine derivative of the general formula (lea):

(wherein R' is a nicotinoyl, 3,4,5-trimethoxybenzoyl or acetylsalicyloyl group) which comprises treating tnonoethanoltaurine (ill):

with an activated derivative R1X of nicotinic 3,4,5-trimethoxybenzoic or acetylsalicylic acid (wherein R is as defined and X is an activating group).

6. A process for preparing a taurine derivative of the general formula (lib):

(wherein R1 is a nicotinoyl, 3,4,5-trimethoxybenzoyl or acetylsalicyloyl group) which comprises treating diethanoltaurine (III):

with an activated derivative R'X of nicotinic 3,4,5-trimethoxybenzoic or acetylsalicylic acid (wherein R' is as defined and X is an activating group).

7. A process for preparing a salt (Ic) of a taurine derivative:

(wherein R1 is a nicotinoyl, 3.4,5ltrimethoxybenzoyl or acetylsalcyloyl group and M is a cation) which comprises reacting a compound of the general formula (V)

(wherein Y is a leaving group and M is a cation) with a salt (VI) of a ,B-acyloxyethylamine: HZ.H2NCH2CH2OR1 (Vl) (wherein Z is an anion and R1 is as defined) in the presence of an acid acceptor to give a compound of the general formula (VII):

(wherein R1 and M are as defined) and acylating the compound (VII) to give the salt (Ic):

8.A process for preparing a salt (Id) of a taurine derivative:

(wherein R' is a nicotinoyl, 3,4,5-trimethoxybenzoyl or acetylsalicyloyl group and M is a cation) which comprises reacting a compound of the general formula (V):

(wherein Y is a leaving group and M is a cation) with a salt (VIII) of a di-(p-acyloxy)ethylamine: HZ.NH(CH2CH2OR1)2 (VII I) (wherein Z is an anion and R' is as defined) in the presence of an acid acceptor.

9. A process for preparing a salt (Id) of a taurine derivative:

(wherein R1 is a nicotinoyl, 3,4,5-trimethoxybenzoyl or acetylsalicyloyl group and M is a cation) which comprises reacting a taurine salt (Xa):

(wherein M is as defined) with a compound of the general formula (IX): YCH2CH2OR1 (IX) (wherein Y is a leaving group and R' is as defined).

10. The conversion of a salt of formula (Ic) or (Id), as defined in Claim 7 or 8 respectively, in to its corresponding free acid, or the conversion of a free acid of formula (la) or (lib), as defined in Claim 5 or 6 respectively, in to a corresponding salt.

11. A taurine derivative of general formula (I) as defined in Claim 1 of use in a method of treatment of the human or animal body.