IE48604B1 - Carboxy(phenyl or tolyl)-sulphonium salts,their preparation and use as anti-obesity agents - Google Patents

Abstract

Novel compounds of formula in which R1 = (C8-24) alkyl, R2 = (C1-6) or unsubstituted or substituted phenyl, R3 = H, halogen, (C1-3) alkyl or alkoxy, R4 = H or (C1-6) alkyl, n = 0 or 1, and Z<(-)>= anion forming a pharmaceutically acceptable non-toxic salt of the corresponding cation, provided that R2 is alkyl when R4 is H, are obtained by alkylation of corresponding alkylthio- or phenylthio-phenyl compounds with alkyl halides in the presence of a metal salt or with a trialkyloxonium tetrafluoroborate after which the resulting anion can be replaced by known anion exchange methods. The compounds are active against obesity and can be incorporated into pharmaceutical compositions.

Description

The invention relates to carboxy-(phenyl or tolyl)-sulphonium salts, their preparation, as well as their use as pharmaceutical agents and to pharmaceutical compositions containing such compounds.

The invention provides compounds of formula I, ® 0 | 4]_(ch2)—c-or4 ,Θ in which is (Οθ_24)alkyl, R2 is (C^_g)alkyl (=R2) or unsubstituted or substituted phenyl of the formula: wherein Y is hydrogen, fluorine, chlorine or bromine, or (C^_4)alkyl or alkoxy, 4-8 6 04Rg is hydrogen, fluorine, chlorine or bromine, or (C^_g)alkyl or alkoxy, R^ is hydrogen, or (C^_g)alkyl (=R^), n is 0 or 1, and Z®is an anion forming a pharmaceutically acceptable non-toxic salt of the corresponding cation; provided that i?2 is alkyl when R^ is hydrogen.

The invention also provides a process for the prep10 aration of compounds of formula I, characterised by reacting a compound of formula (CH2)n-/o-R4 a II in which R' is either R^ or R2 and Rg, R. and n are as 4 defined above, with an alkylating agent transferring an alkyl radical R^ when Ra is R2,or an alkyl radical R2 defined above, when Ra is Rjy in the presence of an anion Z® supplying metal salt in which Z® is as defined above, and, where required, converting the anion Z®in the resulting compound of formula I A into a different anion Z^ by reaction with an acid or salt 20 containing the anion to be introduced. 60 4 The invention particularly provides a process for the preparation of compounds of formula I, characterised by a) producing a compound of formula la, 2)n-C-O-R> Z© la in which is as defined above, by reacting a compound of the formula Ila, COR. i n 4 Ila wherein n, and R^ are as defined above, and Ra is either R^ or Ry, as defined above,· with an alkyl halide of the formula Ilia, Ilia wherein X is bromine or iodine, b a and Rd is either R^ when R is Ry, or is Ry as defined above, when Ra is R^, in the presence of a salt of the formula IV, MZ IV Θ wherein Z is as defined above for Z , and M is a metal forming with X a salt MXj b) producing a compound of formula lb, in which R^, Rj' R3, n and R4 are as defined above, by reacting an alklythio aromatic acid of the formula lib, in which R , R3, R^ and n are as defined above, with a trialkyl oxonium tetrafluoroborate of the formula Illb, (R3) 3 BF Illb in which Rj is as defined above, and, where required, converting the anion Z® in the result10 ing compound of formula I into a different anion Z® by reaction with an acid or salt containing the anion to be introduced.

The alkylation process of the invention, in particular process a), is preferably carried out under essentially anhydrous conditions at moderate temperatures, e.g. from 15°C to 40°C, in an inert solvent, e.g. nitromethane or toluene. The reactants, in particular the compounds Ila and Ilia, are conveniently mixed in the solvent and the salt, e.g. of the formula IV, may be added thereto exercising suitable caution such as shielding from light. The reaction is also preferably carried out under an inert atmosphere, e.g. dry nitrogen. An excess of the alkylating agent, particularly the alkylhalide of formula Ilia, is preferably employed and in most cases is highly desirable in order to increase the yield 6fhhe desired products. The metal in the salt employed, e.g. of formula IV, is chosen such that the resulting salt, e.g, MX is either insoluble or relatively less soluble in the medium than the initial salt employed, e.g. of formula IV. Illustrative of various MZ salts include the salts of noble metals of which silver represents a preferred metal. Other such metals include mercury. Representative anions (Ζθ ) forming such salts include the tetrafluoroborate, trifluoromethylsulphonate and perchlorate ions. Other anions which may be represented by Z include the alkyl and phenyl sulphonates, e.g. methanesulphonate, phenylsulph20 onate and £-toluenesulphonate. Examples of preferred salts of the formula IV include silver trifluoromethylsulphonate and especially silver tetrafluoroborate. The resulting salt MX is separated by known techniques and the desired product is recovered from the solvent phase by applying conventional procedures. It will be appreciated that where a compound la is desired in which Rg 4® other than alkyl, then a compound Ila is used in which Ra = such Rg radical other than alkyl and a compound Ilia is used in which Rb is R^.

Process b) is preferably carried out in an inert solvent, especially methylene dichloride, at moderate temperatures, particularly at room temperature.

Using equivalent amounts of Illb, corresponding compounds lb with R4 = hydrogen are obtained. With excessive amounts of Illb, corresponding compounds lb are obtained in which R^ has the significance of R^.

Conventional anion exchange procedures may be employed to interconvert the anion Z® in the resulting products. For example a compound of the formula I', [ K ] Z® a 1' may be converted into a compound of formula I [ K ] Z® b I in which n, R^, Rg, Rg and R^ are as defined above, K is the cationic portion of compounds I, and z® a and Z®b are different anions Z® forming end products.

More particularly, the compounds of the formula I may be prepared by heating a compound I' in a polar solvent in the presence of an acid of the formula V, H-Z® V b wherein Z® is as above defined, at temperatures typically of from about 55°C to 120°C, preferably 65°C to 100°C, desirably in the presence of a theoretical excess of the acid of the formula V, and separating the desired compound of the formula I from any unreacted starting material by taking advantage of its different solubility characteristics.

Preferred compounds of the formula I' include those in which Z® is the tetrafluoroborate ion. The polar solvent may comprise water and a sufficient amount of a water soluble organic solvent, so that the resulting aqueous 15 co-solvent system is capable of dissolving the starting compound of the formula I' . Examples of such organic solvents are the lower alkanols, e.g. methanol, propanol and preferably ethanol,and dimethylaeetamide and dimethylformamide.

The initial isolation of the desired compound I may be effected by the application of various known procedures depending upon the solubility characteristics of the desired product arid any remaining unreacted starting material. For example, isolation may be readily effected in certain cases simply by lowering the temperature of the reaction to crystallise the desired product by taking advantage of its reduced solubility in the polar solvent. In other cases the contents of the reaction mixture may be concentrated and redissolved in a solvent from which either the desired product or undesired starting material may be selectively crystallised. In still other cases the contents of the reaction mixture may be subjected to standard chromatography procedures or subjected to the action of ion exchange resins.

Another ion exchange procedure that is particularly convenient involves generally conversion of a compound of formula I' , [K] Z® , into a compound of formula I"’ , [K] Z® , by reaction with a compound of formula VI, MOZ®, in a polar solvent, K being as defined above, Mo being a metal cation and Z® and Z® being different anions Z®, MO;Z® and Z® being such that the salt MOZ® is less soluble in the medium than the compound of formula I'*, and the compound VI is more soluble in the medium than the salt formed of formula MOZ® .

This process is more particularly carried out in an aqueous solution at temperatures preferably from 50°C to 120°C, more preferably 80°C to 100°C, preferably with a theoretical excess of the compound VI. An aqueous cosolvent is employed, composed similarly to that used above with ethanol being commonly preferred as the organic component of such solvent system.

By way of illustration, a preferred embodiment of the process involves the use of a compound I', in which Z® is the tetrafluoroborate anion and Mo is potassium whereby the insoluble potassium tetrafluoroborate is formed as a result of the reaction and may be separated from the reaction mixture by taking advantage of its insolubility in the aqueous cosolvent system. In such embodiment the desired compound of the formula I remains in the reaction system cosolvent and may be initially separated from any remaining undesired reactants and starting materials by employing conventional procedures.

Other known ion exchange procedures such as those involving ion exchange resins may be employed, especially when representing a convenient method of separating desired products from reactants and starting materials in those procedures specifically detailed above. Typical ion exchange resins for such use are well known, in effecting the initial isolation of the desired products from ion exchange reactions such as process b) by chroma10 tographic procedures both thin layer and column chromategraphy may of course be employed. Typical chromatography additives for such use are well known, such as silica gel.

Final recovery of the desired compound of the 5 formula I from ion exchange procedures may be also effected by conventional techniques such as crystallisation, precipitation and vacuum distillation.

Starting materials and reagents used in the above described reactions, e.g. compounds Ila, lib. Ilia, Illb, IV and V are either known or may be obtained by known methods.

The compounds of formula I possess pharmacological activity in animals. In particular, the compounds of formula I are indicated for use as anti-obesity agents in the treatment of obesity because they inhibit the passage cf glucose into the blood in mammals, indicated by the glucose transport test in which male Wister rats are dosed orally with 0.3-80 mg/kg body weight of the test compound after at least 20 hours of fasting. One hour after receiving the drug, each animal is sacrificed and the upper small intestine is removed 4830 4 and washed with glucose-saline. A 5 cm section of the intestine is everted so that the mucosal surface is on the outside. One end of the segment is tied and the centre of the sac so formed is filled with oxygen satur5 ated with Kreb's bicarbonate buffer. The other end is then closed to form a sac which is then incubated in 10 ml of oxygen saturated bicarbonate buffer for 60 minutes at 37°C. Both the outside and inside solutions contain initially 0.3% of glucose. At the end of the incubation 10 time, the glucose content of the outer (mucosal) and the inner (serosal) solution is determined using the standard Auto Analyser procedure. Similar tests are run simultaneously with control animals receiving only the vehicle.

The percent inhibition of glucose transport caused by the drug is calculated from the formula: /St " Mt \ I = 100 - ---- x loj c C x wherein I = percent inhibition, = glucose concentration (mg %) of serosal fluid at the end of the experiment in the drug-treated animal, S = glucose concentration (mg %) of serosal c fluid at the end of an experiment in the control animal, 4860 4 Mfc = glucose concentration (mg %) of mucosal fluid at the end of an experiment in the drug-treated animal, and Mc - glucose concentration (mg %) of mucosal 5 fluid at the end of an experiment in the control animal.

For the above-mentioned use, an indicated suitable daily dosage is from about 60 to 3000 mg, suitably administered in divided doses of from 15 to 1500 mg, two to four times daily, or in retard form.

The compounds of formula X may be admixed with conventional pharmaceutically acceptable diluents and carriers, and optionally other excipients and administered preferably orally, for example in the form of tablets or capsules, Preferred significances of the groups R^-R^ are as follows: R1 ^10-20^ alky1' preferably (Ο12_18)alkyl, R2 alkyl or unsubstituted phenyl, more preferably alkyl, R3 hydrogen the carboxy moiety being ortho or para to the sulphonlum ion on the phenyl ring to which both are attached, R4 alkyl, more preferably ethyl. It is particularly preferred that n = 0. « 48604 A preferred group of compounds of formula I are those in which all the groups R^ to R^ have the preferred significances indicated above.

Salts of particular interest generally include 5 the tetrafluoroborate, perchlorate, methanesulphonate, phenylsulphonate and p-toluenesulphonate.

Particularly preferred compounds of formula I are [(o-carbethoxyIphenyl]-(n-propyl)-(n-octadecyl)sulphonium tetrafluoroborate; [ (o-carbethoxy)-phenyl]-(n-propyl)-(n-octadecyl)sulphonium p-toluenesulphonate; and [p-(cc-carbethoxy)-tolyl] -(n-tetradecyl)-(phenyl)sulphonium tetrafluoroborate.

The following Examples illustrate the invention. 15 All temperatures are in degrees Centigrade and room temperature is 20 to 30°C, unless indicated otherwise. 4-8 6 04 EXAMPLE 1: f(o-Carbethoxy)phenyl]-(n-propyl)-(n-octauecyl)sulphonlum tetrafluoroborate (Method a)] To a solution of 11.0 g of 2-(n-octadecylthio) benzoic acid ethyl ester and 4.25 g of n-propyl iodide in 50 ml of methylenedichloride and 200 ml of nitromethane is added 4.9 g of silver tetrafluoroborate. The reaction mixture is stirred at room temperature (under exclusion of light) for sixteen hours and is then filtered free of solids. The filtrate is evaporated under vacuum to dry10 ness. The residue is dissolved in chloroform and chromatographed over silica gel with chloroform containing increasing concentrations of ethanol. The desired fractions are collected and evaporated under vacuum to dryness. From the residue is obtained on crystallisation from ethanol the title compound, m.p. 56-58°.

EXAMPLE 2; [(p-Carbethoxymethyl)phenyl]-(n-tetradecyl)(phenyl)sulphonlum tetrafluoroborate Following the procedure of Example 1 with 8.2 g of 4-(phenylthio)phenylacetic acid ethyl ester and 9.7 g of n-tetradecyl iodide in 100 ml nitromethane as a solvent and adding 5.8 g of silver tetrafluoroborate, from the reaction mixture is obtained the title compound, m.p. 36-38°.

EXAMPLE 3: Repeating the procedure of Example 1, but using corresponding starting compounds in approximately equivalent amounts there are accordingly obtained: a) [(2-carbethoxy-5-methyl)phenyl]-(n-propyl)-(n-octadecyl)sulphonium tetrafluoroborate; b) [ (2-carbethoxy-6-methyl)phenyl]~(n-propyl)-(n-octadecyl)sulphonium tetrafluoroborate; c) [(2-carbethoxy-4-chloro-)phenyl]~(n-propyl)-(n-octa10 decyl)sulphonium tetrafluoroborate; d) [(2-carbethoxy-5-chloro)-phenyl]-(n-propyl)-(n-octadecyl)sulphonium tetrafluoroborate; e) [(4-carbethoxy-2-methoxy)phenyl]-(n-propyl)-(n-octadecyl)sulphonium tetrafluoroborate; f) [(2-carbethoxy-6-methoxy)phenyl]-(n-propyl)-(n-octadecyl)sulphonium tetrafluoroborate; g) [(o-carbethoxy)phenyl]-(n-propyl)-(n-octadecyl)sulphonium perchlorate; h) [(o-carbethoxy)phenyl]-(n-butyl)-(n-octadecyl)sulphon20 ium tetrafluoroborate; i) [(o-carbethoxy)phenyl]-(methyl)-(n-octadecyl)-sulphonium tetrafluoroborate; and j) [(o-carbethoxy)phenyl]-(isopropyl)-(n-octadecyl)sulphonium tetrafluoroborate, m.p. 50-52°. 4-8 604 EXAMPLE 4: Repeating the procedure of Example 2, and using corresponding starting compounds there are accordingly obtained: a) [(3-chloro-4-carbethoxymethyl)phenyl]-(n-tetradecy1)i(phenyl)sulphonium tetrafluoroborate; b) (4-carbethoxymethyl-3-methyl)phenyl]-(n-tetradecyl)(phenyl)sulphonium tetrafluoroborate ? c) (4-carbethoxymethyl-3-methoxy)phenyl]-(n-tetradecyl)10 (phenyl)sulphonium tetrafluoroborate; d) [(4-carbethoxymethyl-3-methyl)phenyl]-(n-tetradecyl)(p-tolyl)sulphonium tetrafluoroborate; e) [p-(σ-carbethoxy)-tolyl]-(n-dodecyl)-(phenyl)sulphonium tetrafluoroborate; and f) fp-(σ-carbethoxy)-tolyl] - (n-octadecyl) -'(phenyl) sulphonium tetrafluoroborate.

EXAMPLE 5: [(o-Carbethoxy)phenyl]-(n-propyl)-(n-octadecyl)sulphonium p-toluene sulphonate To a solution of 5.0 g of [(o-carbethoxy)phenyl)20 (n-propyl)-(n-octadecyl)sulphonium tetrafluoroborate in ml of ethanol is added 20.0 g of potassium tosylate dissolved in a mixture of 200 ml ethanol and 10 ml water.

The reaction mixture is maintained at 80-90° while being stirred vigorously for 2 hours. The reaction mixture is then cooled and filtered, and the filtrate then evaporated under vacuum to dryness to obtain a residue. The residue is taken up in methylene chloride; the organic phase washed several times with water, dried over sodium sulphate, filtered and evaporated under vacuum to dryness. The residue is chromatographed over silica gel three times dsing methylene chloride and increasing amounts of methanol to obtain the title product, m.p. 65-67° EXAMPLE 6: Repeating the procedure of Example 5, but using corresponding starting compounds in approximately equivalent amounts there are accordingly obtained: a) [(o-carbethoxy)phenyl]-(n-propyl)-(n-octadecyl)sulphon15 ium bromide; and b) [(o-carbethoxy)phenyl]-(n-propyl)-(n-octadeeyl)sulphonium trifluoromethylsulphonate.

EXAMPLE 7: C(o-Carbethoxy)phenyl]-(ethyl)-(n-octadecyl)sulphonium tetrafluoroborate [Method b)] To a suspension of 2.0 g 2-(n-octadecylthio)benzoic acid in 150 ml methylene dichloride is added an excess of freshly prepared triethyloxonium tetrafluoroborate. The reaction mixture is stirred at room temperat18 ure for 48 hours. Thereafter the methylene dichloride layer is washed extensively with water, dried over anhydrous sodium sulphate, filtered and evaporated in vacuum to dryness. The crude residue is then chromato5 graphed over silica gel: eluting first with methylene dichloride and then with methylene dichloride containing increasing amounts of methanol. The desired fractions are collected and evaporated in vacuum to dryness thereby giving the title product.

EXAMPLE 8. [p-Carbethoxy)pheny1~3 Σ (n - propyl) - (n - octadecyl) sulphonium tetrafluoroborate (Method a)) To a vessel equipped with a stirrer and maintained under a dry nitrogen gas atmosphere there is added, 150 g of 2 - (n - octadecylthio)benzoic acid ethyl ester, 105 ml of n-propyliodide and 3.0 1 of toluene and stirred until dissolved. To the stirred solution is added, in one portion, 75 g of silver tetrafluoroborate. The reaction mixture is then stirred for 22 hours under the nitrogen atmosphere and protected from light. The resulting mixture is filtered through a*Ce1ite pad (50g) to remove the solids, which are then washed with 250 ml of toluene. The filtrate and washings are combined and evaporated (at 45°/20 mm) to obtain a residue. The residue is then dissolved in 1.5 1 *Celite is a Trade Mark 4860 4 of diethyl ether, and the solution stirred at 5° for 18 hours, resulting in the precipitation of the title product as a white solid (at lower temperatures unreacted starting material co-precipitates). The solid product is washed with 200 ml of cold diethyl ether, then dried (under vacuum at 25°/10 mm) to obtain the refined title product, m.p. 60-63°.

Claims (35)

1. CLAIMS for the production of compounds of formula I, in which R^ is (Cg-C 24 )alkyl, R 2 is C^-Cg)alkyl (=R 2 ) or unsubstituted or substituted phenyl of the formulas wherein Y is hydrogen, fluorine, chlorine or bromine; or (C^^)alkyl or alkoxy, R 3 is hydrogen, fluorine, chlorine or bromine, (C 1 _g)alkyl or alkoxy, R 4 is hydrogen, or (C^g)alkyl (=R^), n is 0 or 1, and Z®is an anion forming a pharmaceuticallyacceptable non-toxic salt of the corresponding cation; provided that R 2 is alkyl when R^ is hydrogen, 5 characterised by reacting a compound of formula II, (CH 2 ) n -C-O-R 4 // II in which R is either Rg or Rg and Rg , R^ and n are as defined above, with an alkylating agent transferring an alkyl radical Rg when R a is R 2 ,or an alkyl radical R 2 defined above, when R a 10 is Rg, in the presence of an anion Z® supplying metal salt in which Z® is as defined above, and, where required, converting the anion Z®in the resulting compound of formula I A into a different anion Z^ by reaction with an acid or salt containing the anion to be introduced. 15

2. A process for the production of compounds of formula I, stated in Claim 1, characterised by a) producing a compound of formula Ia, πΧ> -(GH 2 ) n -C-O-R· ,Θ la in which R^ is as defined above, by reacting a compound of the formula Ila, (CH^COR, Ila wherein n, and R 4 are as defined above, and R a is either R^ or Rj, as defined above, 5 with an alkyl halide of the formula Ilia, Ilia wherein X is bromine or iodine, and R b is either R^ when R a is Rj, or is B R 2 as defined above, when R is R^, in the presence of a salt of the formula IV, MZ IV wherein z is as defined above for Z®, and M is a metal forming with X a salt MX; b) producing a compound of formula lb, by reacting an alkylthio aromatic acid of the formula lib, in which R^, Rg, R^ and n are as defined above, 5 with a trialkyl oxonium tetrafluoroborate of the formula Illb, © (R£)g O BF 4 a Illb in which Rg is as defined above, and where required, converting the anion Z® in the resulting compound of formula I into a different anion Z® 10 by reaction wi th an acid or salt containing the anion to be introduced.

3. A process for the production of a compound of formula I, stated in Claim 1, substantially as described in any one of the Examples. 15 4. A compound of formula I, stated in Claim 1, whenever prepared by a process as claimed in Claim 1, 2 or 3

4. -8 60 4

5. A compound of formula I, stated in Claim 1.

6. A compound as claimed in Claims 4 or 5 in which Rg is (Cgg_2Q)alkyl.

7. A compound as claimed in Claims 4 or 5 in 5 which R. is (c ,)alkyl or unsubstituted phenyl. ~ 1“D

8. A compound as claimed in Claims 4 or 5 in which Rg is hydrogen.

9. A compound as claimed in Claims 4 or 5, in which the carboxy moiety is ortho or para to the sulph10 onium ion on the phenyl ring.

10. A compound as claimed in Claims 4 or 5 in which R 4 is (Cg_ g )alkyl.

11. A compound as claimed in Claims 4 or 5 in tetrafluoroborate, perchlorate, methanesulphonate, phenyl15 sulphonate or p-toluenesulphonate salt form.

12. [(o-Carbethoxy)phenyl]-(n-propyl)(n-octadecyl)sulphonlum tetrafluoroborate.

13. [(o-Carbethoxy)-phenyl]-(n-propyl)-(noctadecyl)sulphonlum p-toluenesulphonate. 20

14. [p-(α-Carbethoxy)-tolyl]-(n-tetradecyl)(phenyl)sulphonlum tetrafluoroborate.

15. [ (2-Carbethoxy-5-methyl)phenyl]-(n-propyl)(n-octadecyl)sulphonlum tetrafluoroborate.

16. . f (2-Carbethoxy-6-methyl) phenyl] - (n-propyl) (n-octadecyl)sulphonium tetrafluoroborate.

17. [(2-Carbethoxy-4-chloro-)phenyl]-(n-propyl) (n-octadecyl)sulphonium tetrafluoroborate. 5

18. [(2-Carbethoxy-5-chloro)-phenyl]-(n-propyl)(n-octadecyl)sulphonium tetrafluoroborate.

19. [(4-Carbethoxy-2-methoxy)phenyl]-(n-propyl) (n-octadecyl)sulphonium tetrafluoroborate.

20. [(2-Carbethoxy-6-methoxy)-phenyl]-(n-propyl) 10 (n-octadecyl)sulphonium tetrafluoroborate.

21. [(o-Carbethoxy)-phenyl]-(n-propyl)-(noctadecyl)sulphonium perchlorate.

22. '[(o-Carbethoxy)phenyl]-(n-butyl)-(n-octadecyl) sulphonium tetrafluoroborate. 15

23. [(o-Carbethoxy)-phenyl]-(methyl)-(n-octadecyl)-sulphonium tetrafluoroborate.

24. [(3-Chloro-4-carbethoxymethyl)-phenyll-(ntetradecyl)-(phenyl)sulphonium tetrafluoroborate.

25. [4-Carbethoxymethyl-3-methyl)phenyl]-(n20 tetradecyl)-(phenyl)sulphonium tetrafluoroborate.

26. [4-Carbethoxymethyl-3-methoxy)-phenyl]-(ntetradecyl)-(phenyl)sulphonium tetrafluoroborate.

27. [(4-Carbethoxymethyl-3-methy1)phenyl]-(n26 tetradecyl)-(p-tolyl)sulphonium tetrafluoroborate.

28. [p-(α-carbethoxy)-tolyl]-(n-dodecyl)(phenyl)sulphonium tetrafluoroborate.

29. [p-(σ-Carbethoxy)-tolyl]-(n-octadecyl)5 (phenyl)sulphonium tetrafluoroborate.

30. [(o-Carbethoxy)phenyl]-(n-propyl)(n-octadecyl)sulphonium bromide.

31. [(o-Carbethoxy)phenyl]-(n-propyl)-(n-octadecyl)sulphonium trifluoromethylsulphonate. 10

32. ((o-Carbethoxy)phenyl]-(ethyl)-(n-octadecyl)sulphonium tetrafluoroborate.

33. [(o-Carbethoxy)phenyl]-(isopropyl)-(n-octadecyl) -sulphonium tetrafluoroborate.

34. A pharmaceutical composition comprising a 15 compound according to any one of Claims 4 to 33, in association with a pharmaceutically acceptable diluent or carrier.

35. A compound as claimed in any one of Claims 4 to 33 for use as an anti-obesity agent.