NOVEL COMPOUNDS

Abstract: Compounds of formula (I) are disclosed, processes for their preparation, pharmaceutical compositions containing the compounds and the use of the compounds as pharmaceuticals. There are also provided chemical intermediates useful for the preparation of the compounds. The compounds are useful as pharmaceuticals, especially for the treatment of inflammatory disease.

Description: NOVEL COMPOUNDS The present invention relates to novel compounds, processes for their preparation, pharmaceutical compositions containing the compounds and the use of the compounds as pharmaceuticals. There are also provided chemical intermediates useful for the preparation of the compounds. According to the invention, there is provided a compound of formula I wherein :- R represents hydrogen, Cl to 12 alkyl, phenyl or a 5 or 6 membered heterocyclic ring containing from 1 to 3 atoms selected from O, N or S, which alkyl, phenyl or heterocyclic ring is optionally substituted by halogen, or which alkyl is optionally substituted by a group J, where J is phenyl or phenyl fused with one or two benzene rings, or biphenylyl, optionally ring substituted by 1 to 3 heteroatoms selected from O, N or S, each group J being optionally substituted by Cl to 6 alkyl, hydroxy, Cl to 6 alkoxy, nitro or halogen; 2 3 for R and R :- 2 10 (i) R represents hydrogen, Cl to 6 alkyl or R -B; and 3 10 R represents hydrogen, Cl to 6 hydroxyalkyl, C3 to 9 alkenylcarboxyl or R -B, wherein R represents Cl to 6 alkyl and B represents COOH, PO3H2, OPO3H2, SO3H, OSO3H, tetrazolyl, CONR 1 l OU or CONHSO2R 1 R 1 l representing hydrogen or Cl to 6 alkyl; or 2 3 (ii) R and R together represent a benzo ring or a six membered aromatic heterocyclic ring containing 1 to 3 nitrogen atoms, which benzo or heterocyclic 4 4 ring is optionally substituted by R , wherein R represents hydrogen, Cl to 6 alkoxy, Cl to 6 carboxyalkoxy, C3 to 9 alkenylcarboxyl, R -B or -(CH 2 ) p CO 2 PG, wherein R represents Cl to β lkyl and B represents COOH, PO3H2, OPO3H2, SO3H, OSO3H, tetrazolyl, CONR 1 ! OH or CONHSO2R 1 R 1 * representing hydrogen or Cl to 6 alkyl, and PG is allyl or tert-butyl and p represents zero or an integer from 1 to 6; 8 9 R and R independently represent hydrogen, methyl, Cl to 6 alkyl, aryl or heteroaryl, or 8 9 together R and R represent C3 to 6 cycloalkyl or a 3, 4, 5 or 6 membered heterocyclic ring containing from 1 to 3 atoms selected from O, N or S; Ar represents phenyl, or phenyl fused with one or two benzo rings, or biphenylyl optionally ring substituted with 1 to 3 heteroatoms selected from O, N or S, each Ar group being optionally substituted by Cl to 6 alkyl, hydroxy, Cl to 6 alkoxy, nitro or halogen; X represents O, S, SO2, CH 2 or SO; Y represents O, NR or (CH2) a , where a represents an integer from 1 to 12 and R represents hydrogen or Cl to 6 alkyl; Z represents O, S, CH=CH, N=N, N=CH or NR , where R represents hydrogen or Cl to 6 alkyl; and n represents an integer from 1 to 12; or a pharmaceutically acceptable salt, enantiomer or tautomer thereof. According to the invention, there is also provided a compound of formula I or a pharmaceutically acceptable salt, enantiomer or tautomer thereof, for use as a pharmaceutical. Another aspect of the invention provides the use of a compound of formula I or a pharmaceutically acceptable salt, enantiomer or tautomer thereof, in the manufacture of a medicament, for the treatment or prophylaxis of inflammatory disease. The invention further provides a method of treating, or reducing the risk of, inflammatory disease in a patient suffering from, or at risk of, said disease, wherein the method comprises administering to the patient a compound of formula I or a pharmaceutically acceptable salt, enantiomer or tautomer thereof. Suitably R represents hydrogen, Cl to 12 alkyl, phenyl or a 5 or 6 membered heterocyclic ring containing from 1 to 3 atoms selected from O, N or S, which alkyl, phenyl or heterocyclic ring is optionally substituted by halogen, or which alkyl is optionally substituted by a group J, where J is phenyl or phenyl fused with one or two benzene rings, or biphenylyl, optionally ring substituted by 1 to 3 heteroatoms selected from O, N or S, each group J being optionally substituted by Cl to 6 alkyl, hydroxy, Cl to 6 alkoxy, nitro or halogen. Examples of suitable 5 or 6-membered heterocyclic rings include thiophene, furan, pyrrole, pyridyl and pyrimidine rings. Preferably, R represents phenyl, dichlorophenyl (eg, 3,5- or 3,4-dichlorophenyl) or methyl. More preferably R represents phenyl or dichlorophenyl. 2 Preferably, R represents hydrogen, methyl or -(CH2)4CO2H. 3 Preferably, when R is according to option (i), it represents hydrogen, -(CH2)2OH, -CO2H, -(CH 2 )3CO 2 H, -(CH 2 )2CO 2 H or CH=CH-CO 2 H. 2 3 4 Preferably, when R and R are according to option (ii), R represents hydrogen, OMe, -CO 2 H, -(CH 2 )2CO 2 H, -OCH 2 CO 2 H or -(CH 2 ) p CO 2 PG, where PG is ally, or tert-butyl 2 3 and p represents zero or an integer from 1 to 6. More preferably when R and R are 4 according to option (ii), R represents hydrogen, OMe, -CO2H, -(CH2)2CO2H or -OCH 2 CO 2 H. Preferably, a represents an integer from 1 to 3. Preferably, Y represents O or CH2. Preferably, X represents O or S or SO2. Preferably, Z represents O, S, CH=CH, NH or NMe. Preferably, n represents 1, 5 or 9. 8 „ Preferably, R represents hydrogen or methyl. More preferably R represents hydrogen. 9 9 Preferably, R represents hydrogen, methyl, phenyl or isopropyl. More preferably R represents hydrogen. Preferred compounds are those exemplified herein, both in free base form and as pharmaceutically acceptable salts. Chemical intermediates of formulae LT to XXI are useful for producing compounds of formula I or pharmaceutically acceptable salts, enantiomers or tautomers thereof. Novel intermediates of formulae LI to XXI form a further aspect of the invention. Formulae II to XXI are as follows:- II R1— (CH 2 )n— LG XVIII wherein 1 2 4 8 9 R , R , R , R , R , X, Y and n are as defined above; Z is as defined above or represents N-C(Ph3); R 3 is as defined above, or represents -CH=CHCO 2 R 6 , -CHO or -(CH 2 )2OTBDMS, wherein TBDMS is dimethyl( 1 , 1 -dimethylethyl)silyl; R represents hydrogen or Cl to 6 alkyl; 7 R represents hydrogen, NH2 or halogen; L and LG each represents a leaving group; Ha represents halogen; A represents hydrogen or halogen; and r represents zero or an integer from 1 to 6. In preferred embodiments of formulae LI to VI:- =tert- uty . In preferred embodiments of formulae VLI toXLl:- X = O or S; Y = 0; Z = O or NH; R 1 = phenyl, 3,5-dichlorophenyl or 3,4-dichlorophenyl; R 4 = H, OMe, OCH 2 C0 2 PG or (CH 2 ) p C0 2 PG, where p=0 or 2; n = 1 or 5; PG = allyl, hydrogen or tert-butyl. In preferred embodiments of formulae XLLl to XV:- X = 0; Y = CH 2; R 1 = phenyl; n = 5. In preferred embodiments of formulae XVI to XXI:- r = 0, 2 or 3; R = hydrogen or methyl; and 7 R = hydrogen, Br or NH2. The process mentioned above, for the preparation of compounds of formula I or their pharmaceutically acceptable salts, enantiomers or tautomers, comprises:- (a) reacting a compound of formula TV, or a pharmaceutically acceptable salt, enantiomer or tautomer thereof, with a compound of formula V, or a pharmaceutically acceptable salt, enantiomer or tautomer thereof, wherein formulae IV and V are as defined above; or (b) reacting a compound of formula IV, or a pharmaceutically acceptable salt, enantiomer or tautomer thereof, with a compound of formula VI, or a pharmaceutically acceptable salt, enantiomer or tautomer thereof, wherein formulae TV and VI are as defined above; or (c) oxidising a compound of formula XLI, or a pharmaceutically acceptable salt, enantiomer or tautomer thereof, wherein formula XLI is as defined above; or (d) preparing a compound of formula I, or a pharmaceutically acceptable salt, enantiomer or tautomer thereof, wherein X represents SO2, by oxidising a compound of formula I, or a pharmaceutically acceptable salt, enantiomer or tautomer thereof, wherein X represents S. In options (a) and (b), the reaction may for example be performed in the presence of BuLi. In option (c), Dess-Martin oxidation may for example be used. In option (d), oxidation may for example be performed using oxone. Compounds of formula IV may be prepared by reaction of compounds of formula LLI with the following compound: - O XXII Ha > wherein Ha represents halogen (preferably Br) and L is as defined above. The reaction may be performed in the presence of a base. Compounds of formula LU may be prepared by reaction of compounds of formula LI with the following compound:- XXIII wherein X and Y are as defined above. The reaction may be performed in the presence of a base. Compounds of formula XLI may be prepared by reaction of compounds of formula X with compounds of formula XI. Compounds of formula X may be prepared by reaction of compounds of formula LX with an acyl halide in an alcohol, eg acetyl chloride in ethanol. Compounds of formula LX may be prepared by reaction of compounds of formula VLI with the following compound:- XXIV H ^ N This reaction is performed in the presence of TEA (triethylamine). Compounds of formula VLLI may be prepared by reaction of compounds of formula VLI, XIV or XV with Dibal-H (diisobutylaluminium hydride). Compounds of formula VLI may be prepared by reaction of compounds of formula LLI with the following compound: - wherein Ha represents halogen, preferably Br. This reaction may be performed in the presence of a base. Compounds of formula XV may be prepared from compounds of formula XIV. The conditions for this reaction are firstly, hydrolysis of the ester to the acid. Then conversion of the acid to acid chloride. Then reaction of the acid chloride with N-methoxy-N- methylamine to give XV. Compounds of formula XLV may be prepared by reacting compounds of formula XIII with compounds of formula LI. This reaction may be performed in the presence of base. The thiazole intermediates of formula XLX may be prepared by reacting compounds of formula XVLLΪ with LiOH in a suitable solvent, eg THF-H2Q- Compounds of formula XVLLI may be prepared by reacting compounds of formula XVLI with formamide in the presence of P2S5. Compounds of formula XVII may be prepared by reacting compounds of formula XVI with Ha2 (where Ha represents halogen, preferably Br) in the presence of an alcohol, eg methanol. in a suitable solvent, eg THF-H2O. Compounds of formula XXI, wherein R represents said 7 alkyl may be prepared by reacting compounds of formula XXI, wherein R represents NH2 and R represents said alkyl with TMSHa, wherein TMS represents trimethylsilyl and Ha represents said halogen, in the presence of tert-butylONO. Compounds of formula XXI, where said alkyl may be prepared by reacting compounds o ormu a X, wherein R represents said alkyl and Ha represents halogen (preferably Br), with thiourea. Compounds of formula XX may be prepared by reacting compounds of formula XVI with TMSHa (preferably TMSBr) in DMSO. Compounds of formula LI, XHL, XVI and XXLI to XXV are known and or may be prepared by conventional methods. Pharmaceutically acceptable derivatives of the compounds of formula I include esters, amides, salts and hydrates. Salts of the compounds of formula I include metal ion salts, eg alkali metal and alkaline earth metal salts, and addition salts with suitable bases, eg suitable amines such as dicyclohexylamine and 1-adamantanamine. "Alkyl" includes straight chain, branched, cyclic, saturated or unsaturated alkyl. "Hydroxyalkyl", "carboxyl", "alkoxy" and "carboxyalkoxy" are interpreted similarly. The compounds of formula I may exist in enantiomeric forms, all enantiomers, racemates and mixtures thereof are included within the scope of the invention. The various optical isomers may be isolated by separation of a racemic mixture of the compounds using conventional techniques, e.g. fractional crystallisation, or HPLC. Alternatively the individual enantiomers may be made by reaction of the appropriate optically active starting materials under reaction conditions which will not cause racemisation. Intermediate compounds may also exist in enantiomeric forms and may be used as purified enantiomers, racemates or mixtures. The compounds of formula I, and pharmaceutically acceptable salts, enantiomers and tautomers thereof, are useful because they possess pharmacological activity in animals. The invention therefore provides a compound of formula (I) as defined herein as a therapeutic agent. In particular, the compounds are useful as anti-inflammatory agents. The compounds are indicated for use in the treatment or prophylaxis of inflammatory conditions in mammals including man. Conditions that may be specifically mentioned are: osteoarthritis, rheumatoid arthritis, rheumatoid spondylitis, gouty arthritis and other arthritic conditions, inflamed joints; eczema, psoriasis, dermatitis or other inflammatory skin conditions such as sunburn; inflammatory eye conditions including uveitis and conjunctivitis; lung disorders in which inflammation is involved, eg asthma, bronchitis, pigeon fancier's disease, farmer's lung, acute respiratory distress syndrome, bacteraemia, endotoxaemia (septic shock) and pancreatitis; conditions of the gastrointestinal tract including aphthous ulcers, gingivitis, Crohn's disease (a condition of the small and sometimes also of the large intestine), atrophic gastritis and gastritis varialoforme (conditions of the stomach), ulcerative colitis (a condition of the large and sometimes of the small intestine), coeliac disease (a condition of the small intestine), regional ileitis (a regional inflammatory condition of the terminal ileum), peptic ulceration (a condition of the stomach and duodenum) and irritable bowel syndrome; pyresis, pain; damage to the gastrointestinal tract resulting from infections by, eg Helicobacter pylori, or treatments with non-steroidal anti-inflammatory drugs; and other conditions associated with inflammation, particularly those in which phospholipid, lipoxygenase and cyclooxygenase products are a factor. For the above mentioned therapeutic indications, doses administered will, of course, vary with compound employed, the mode of administration and the treatment desired. However, in general, satisfactory results are obtained when the compound is administered at a daily dosage of from about 0.1 mg to about 20 mg per kg of animal body weight, preferably given in divided doses 1 to 4 times a day or in sustained release form. For man the total daily dose is in the range of from 7.0 mg to 1400 mg and unit dosage forms suitable for oral administration comprise from 2.0 mg to 1400 mg of the compound admixed with a solid or liquid pharmaceutical diluent or carrier. Topical administration of the compounds of invention or their pharmaceutically acceptable salts, enantiomers or tautomers is also contemplated. The compounds of formula I may be used on their own or in the form of appropriate medicinal preparations for enteral, parenteral or topical administration. For example there is provided a pharmaceutical composition comprising a compound of formula I, or a pharmaceutically acceptable derivative thereof, in admixture with a pharmaceutically acceptable adjuvant, diluent or carrier. The composition comprises preferably less than 80% and more preferably less than 50% by weight of the compound of formula I or a pharmaceutically acceptable salt, enantiomer or tautomer thereof. Examples of such adjuvants, diluents and carriers are: for tablets and dragees - lactose, starch, talc, stearic acid; for capsules - tartaric acid or lactose; for injectable solutions - water, alcohols, glycerin, vegetable oils; for suppositories - natural or hardened oils or waxes. Compositions in a form suitable for oesophageal administration include tablets, capsules and dragees; compositions in a form suitable for administration to the lung include aerosols, particularly pressurised aerosols; compositions in a form suitable for administration to the skin include creams, eg oil-in-water emulsions or water-in-oil emulsions; compositions in a form suitable for administration to the eye include drops and ointments. In a further aspect the invention provides a method of treatment of the above disorders which comprises administering to the patient a compound of formula (I) as defined herein or a pharmaceutically acceptable salt, enantiomer or tautomer thereof. In a still further aspect the invention provides the use of a compound of formula (I) as defined herein in the manufacture of a medicament for the treatment of the above disorders. The invention is illustrated by the following examples: EXAMPLE 1 2-r2-(4-(5-Phenylpentylthio)phenoxy)-l-oxoethyllbenzoxazole-5-carboxylic acid a) (l.l-Dimethyl)ethyl 3-nitro-4-hvdroxybenzoate s A mixture of DCC (33.0g), ( 1 , 1 -dimethyl)ethyl alcohol (300 ml) and 3-nitro-4- hydroxybenzoic acid (27.50g) in THF (150 ml) was treated with DMAP (0.5g) and stirred at 25°C for 18 hrs. A solid formed (DCU) which was filtered off and discarded. The filtrate was dissolved in ethyl acetate and hexane added to precipitate out further DCU which was removed by filtration. The filtrate was concentrated to a gum which was passed down a o silica gel column eluted with hexane:ethyl acetate (9: 1, v/v). The product was isolated as a solid (3.65g). Mass spectrum : m/e 239 1H NMR, CDC1 3 , d: 1.61 (s, 9H), 1.19 (d, 1H,), 8.17-8.20 (dd, 1H), s 8.74 (d, 1H). b) (l.l-Dimethyl)ethyl 3-amino-4-hvdroxybenzoate A solution of the product from la (3.25g) in ethyl acetate (100 ml) was treated with 0 10%Pd/C (0.25g) and stirred under an atmosphere of hydrogen gas at 3 bar for 4 hrs. The reaction mixture was filtered through celite and evaporated to give the required product as a solid (2.84g). Mass spectrum : m/e 209 5 1H NMR, DMSO- D6 , d: 1.49 (s, 9H), 3.38 (bs, 2H), 4.73 (bs, 1H) 6.68 (d, 1H), 7.03-7.06 (dd, 1H), 7.17 (d, 1H). c) 5-Phenylpentyl mesylate 0 5-Phenylpentanol (6.0g) and triethylamine (5.6 ml) were dissolved in dry THF (50 ml) and cooled to -5°C. A solution of methanesulphonic anhydride (6.7g) in dry THF (20 ml) was added dropwise. The reaction mixture was stirred at 25°C for 3 hrs and then evaporated. The residue was dissolved in ethyl acetate, washed with 2N hydrochloric acid, water, brine, dried (MgSO-i) and evaporated to give the product as an oil (7.3g). 5 Mass spectrum: m e 326 NMR: CDCI 3 d: 1.45 (m, 2H), 1.67 (m, 4H), 1.78 (m, 2H), 2.63 (t, 2H), 2.98 (s, 3H), 4.24 (t, 2H), 7.18 (m, 3H), 7.29 (m, 2H). d) 4-(5-Phenylpentylthio)pheπol 5-Phenylpentyl mesylate (35.3g), 4-hydroxythiophenol (18.9g), caesium carbonate (47.6g) in acetonitrile were heated at reflux for 8 hrs. The mixture was then poured into water and extracted with ethyl acetate. The extract was washed with water, dried (MgSO 4 ) and evaporated to give an oil. This was passed down a silica gel column eluted with hexane:ethyl acetate (5: 1) to afford the product as a white solid, (33g). NMR: CDCI 3 d: 1.43 (m, 2H), 1.60 (m, 2H), 2.59 (t, 2H), 2.8 (t, 2H), 4.83 (s, 1H), 7.17 (m, 3H), 7.27 (m, 2H). e) 2-r4-(5-Phenylpentylthio)phenoxy1acetonitrile 4-(5-Phenylpentylthio)phenol (2.73g), bromoacetonitrile (1.44g) and caesium carbonate (4.8g) in acetonitrile (50 ml) were heated at reflux for 4 hrs, with stirring. The reaction mixture was allowed to cool to 25°C, poured into 2N hydrochloric acid (300 ml) and extracted with ethyl acetate. The combined organic extracts were washed with water, brine, dried (MgSO 4 ) and the solvent was evaporated under reduced pressure to give an oil. This was passed down a silica gel column eluted with hexane:dichloromethane (1:1, v/v). The appropriate fractions were collected and evaporated to give the required product as a clear colourless oil, (2.39g). Mass spectrum m/e 311 1 H NMR, CDCl 3 , d: 1.40-1.48 (m, 2H), 1.57-1.67 (m, 4H), 2.59 (t, 2H), 2.84 (t, 2H), 4.73 (s, 2H), 6.91 (d, 2H), 7.16 (m, 3H), 7.30 (m, 2H), 7.35 (d, 2H). f) 2-r4-(5-Phenylpentylthio)phenoxy1acetaldehvde A stirred solution of 2-[4-(5-phenylpentylthio)phenoxy]acetonitrile (2.0g) in dry toluene (10 ml) was cooled to -45°C under a nitrogen atmosphere. A 1M solution of Dibal-H in toluene (9.5 ml) was added dropwise and the resulting solution was allowed to warm to 0°C over 1 hr and stirred at this temperature for a further 1 hr. A saturated solution of ammonium chloride (15 ml) was added followed by diethyl ether (15 ml). A solution of concentrated sulphuric acid (6 ml) in water ( 24 ml) was then added and the mixture was stirred at 25°C for 18 hrs. The mixture was added to ethyl acetate (500 ml), the separated organic phase washed with water, brine, dried (MgSO 4 ) and the solvent was evaporated to give the product as a yellow oil, (1.66g). Mass spectrum : m e 314 Η NMR, CDC1 3 , d: 1.43-1.47 (m, 2H), 1.59-1.65 (m, 4H), 2.58 (t, 2H) 2.81 (t, 2H), 4.54 (s, 2H), 6.82 (d, 2H), 7.16 (m, 3H), 7.26 (m, 2H), 7.36 (d, 2H). g) 3-r4-(5-Phenylpentylthio)phenoxy1-2-hvdroxypropionitrile 2-[4-(5-Phenylpentylthio)phenoxy]acetaldehyde (1.56g), acetone cyanohydrin (0.7 ml) and triethylamine (1 drop) in dichloromethane (20 ml) were stirred at 25°C for 18 hrs. The solvent was evaporated to afford a yellow solid. The solid was passed down a silica gel column eluted with dichloromethane:methanol (50: 1, v/v). The appropriate fractions were combined and evaporated to afford the required product as a white solid (0.95g). 1H NMR, CDC1 3 , d: 1.41-1.48 (m, 2H), 1.58-1.65 (m, 4H), 2.59 (t, 2H), 2.83 (t, 2H), 3.00 (d, 1H), 4.18-4.25 (m, 2H), 4.79-4.84 (m, 1H), 6.87 (d, 2H), 7.14-7.19 (m, 3H), 7.25-7.30 (m, 2H), 7.33 (d, 2H). h) 3-r4-(5-PhenylpentvIthio)phenoxy]-2-hvdroxy-l-ethoxy-l-inιinopropane hvdrochloride Ethanol (3.0g) in chloroform (25 ml) was cooled to 0°C and stirred under an atmosphere of nitrogen gas. Acetyl chloride (4. Ig) was added and the mixture stirred at 0°C for 0.5 hr. (3-[4-(5-phenylpentylthio)phenoxy]-2-hydroxypropionitrile (0.94g) was added and the mixture was allowed to warm to 25°C over 1 hr and stirred at this temperature for a further 18 hrs. The solvent was evaporated to give the required product as a white solid (1). This was used directly in the next step. i) (l,l-Dimethyl)ethyl 2-f2-(4-(5-phenylpentylthio)phenoxy)-l- hvdroxyethyllbenzoxazole-5-carboxyIate The product from lh (1.26g) and the product from lb (0.85g) in acetonitrile (30 ml) were heated at reflux for 6 hrs. The reaction mixture was cooled to 25°C, poured into ethyl acetate (500 ml), washed with water, brine, dried (MgSO ) and evaporated to give a gum. This was passed down a silica gel column eluted with hexane:ethyl acetate (4:1, v/v) to give the product as an oil, (1.20g). Η NMR, CDC1 3 , d: 1.40-1.46 (m, 2H), 1.55-1.60 (m, 4H), 1.62 (s, 9H), 2.58 (t, 2H), 2.80 (t, 2H), 3.80 (d, 1H) 4.44-4.53 (m, 2H) 5.33-5.38 (m, 1H), 6.85 (d, 2H), 7.13-7.19 (m, 3H), 7.25-7.29 (m, 2H), 7.31 (d, 2H), 7.55 (d, 1H), 8.05-8.07 (dd, 1H), 8.39 (d, 1H). i) (l.l-Dimethyl)ethyl 2-r2-(4-(5-phenylpentylthio)phenoxy)-l-oxoethvnbenzoxazoIe- 5-carboxylate The product from li (0.54g, 1 mmol) was dissolved in dichloromethane (25 ml), treated with Dess-Martin reagent (0.75g) and stirred at 25°C for 4 hrs. The reaction mixture was mixed with ethyl acetate (200 ml), washed with a 10% aqueous solution of sodium thiosulphate (3 x 200 ml), brine and dried (MgSO 4 ). The solvent was evaporated to give a yellow gum. This was passed down a silica gel column eluted with hexane:ethyl acetate (9: 1) to give the product as a yellow solid, (0.23g). Mass spectrum: m e 550 (M+NH 4 ) Η NMR, CDC1 3 , d: 1.41-1.47 (m, 2H), 1.58-1.62 (m, 4H), 1.64 (s, 9H), 2.59 (t, 2H), 2.83 (t, 2H), 5.55 (s, 2H), 6.95 (d, 2H), 7.15-7.19 (m, 3H), 7.23-7.30 (m, 2H), 7.35 (d, 2H) 7.71 (d, 1H), 8.26 (dd, 1H), 8.57 (d, 1H). k) 2-r2-(4-(5-Phenylpentylthio)phenoxy)-l-oxoethyll benzoxazoIe-5-carboxylic acid A solution of the product from lj (0.2g) in formic acid (10 ml) and dichloromethane (5 ml) was stirred at 25°C for 3 hrs. Toluene (20 ml) was added and the mixture was evaporated. This procedure was repeated twice to afford a yellow solid which was recrystallised from acetonitrile to give the required product (0.09g). Mass spectrum: m e 474 (M-H) M.p.: 148-149°C C 27 H 25 NO 5 S requires: C 68.2 H 5.3 N 3.0 S 6.7 % found: C 68.1 H 5.4 N 3.1 S 6.7 % EXAMPLE 2 l-Methyl-2-f2-r4-(5-phenylpentylthio)phenoxyl-l-oxoethvnbenzimidazole a) Ethyl 2-r4-(5-phenylpentylthio)phenoxy1acetate 4-(5-Phenylpentylthio)phenol (2.0g) was dissolved in acetonitrile (60 ml) and ethyl 2- bromoacetate (1.23g) was added. The mixture was treated with caesium carbonate (3.58g) and stirred at 25°C for 18 hrs. Water (50 ml) was added and the mixture was extracted with ethyl acetate. The combined extract was washed with saturated sodium bicarbonate, water, brine, dried (MgSO 4 ) and evaporated to give the product as a solid, (2.32g). Η NMR, CDC1 3 , d: 1.30 (t, 3H), 1.38-1.48 (m, 2H), 1.56-1.66 (m, 4H), 2.59 (t, 2H), 2.81 (t, 2H), 4.27 (q, 2H), 4.60 (s, 2H), 6.84 (d, 2H), 7.14-7.20 (dd, 2H), 7.25 (m, 3H), 7.32 (d, 2H). b) l-Methyl-2-r2-r4-(5-Phenylpentylthio)phenoxy1-l-oxoethvnbenzimidazole A stirred solution of 1-Methylbenzimidazole (0.223g) in dry THF (30 ml) was cooled to - 78°C under a nitrogen atmosphere. Butyl lithium ( 1.6M in hexane, 1.06 ml,) was added dropwise and the solution stirred at below -60°C for 15 mins. The ester prepared in 2a, (0.60g) in THF (10 ml) was added dropwise over 5 mins, and the reaction was stirred at below -60°C for 0.5 hr. Cooling was removed and the reaction was allowed to attain ambient temperature. Diethyl ether (100 ml) and 2N hydrochloric acid (50 ml) were added and the two layers separated. The aqueous layer was extracted with ether, the combined ether extract was washed with water, brine, dried (MgSO ) and evaporated to a colourless oil. The oil was passed down a silica gel column eluted with hexane:ethyl acetate (4:1, v/v). The appropriate fractions were combined and evaporated to give a white solid which was recrystallised from acetonitrile to afford the product, (0.35g). Mass spectrum: m/e 445 (M+H) M.p.: 94-95°C C 27 H 28 N 2 O 2 S requires: C 72.9 H 6.4 N 6.3 S 7.2 % found: C 73.0 H 6.1 N 6.4 S 7.2 % EXAMPLE 3 5-(2-Hydroxyethyl)-4-methyl-2-r2-(4-(5-phenylpentvIthio)phenoxy)-l- oxoethyllthiazole a) 5-(2-(Dimethyl(l.l-dimethylethyl)siIyloxy)ethyl)-4-methylthiazole 5-(2-Hydroxyethyl)-4-methylthiazole (15.0g) was dissolved in DMF (80 ml) and imidazole (7.15g) was added. The reaction was cooled to 0°C and t-butyldimethylsilylchloride (15.8g) in DMF (100 ml) was added dropwise over 1 hr. The reaction was stirred at 25°C for 18 hrs, water (100 ml) was added and the mixture was extracted with ethyl acetate. The extract was washed with water, dried (MgSO4) and evaporated to give an oil. This was passed down a silica gel column eluted with hexane:ethyl acetate (3:2, v/v) to give the product as a colourless oil (23.74g). 1H NMR, CDC1 3 , d: 0.01 (s,6H), 0.87 (s, 9H), 2.39 (s, 3H), 2.94 (t, 2H), 3.76 (t, 2H), 8.55 (s, 1H). b 5-(2-(Dimethyl(Ll-dimethylethyl)silyloxy)ethyl)-4-methyl-2-r2-(4-(5- phenylpentylthio)phenoxy)-l-oxoethyllthiazole Using the procedure described for example 2b but using the thiazole derivative prepared in example 3 a, in place of 1-methylbenzimidazole led to the preparation of the required compound as an oil in 79% yield. Η NMR, CDC1 3 , d: 0.02 (s, 6H), 0.88 (s, 9H), 1.40-1.48 (m, 2H), 1.56-1.66 (m, 4H), 2.45 (s, 3H), 2.59 (t, 2H), 2.81 (t, 2H), 3.02 (t, 2H), 3.83 (t, 2H), 5.46 (s, 2H), 6.92 (d, 2H), 7.14-7.19 (dd, 2H), 7.26 (m, 3H), 7.31 (d, 2H). c) 5-(2-Hvdroxyethyl)-4-methyl-2-f2-(4-(5-phenylpentylthio)phenoxy)-l- oxoethyll thiazole The silyl ether prepared in 3b (0.62g,) was dissolved in dry THF (5 ml) and treated with a IM solution of TBAF in THF (3.3 ml). The mixture was stirred at 25°C for 1 hr. Water (70 ml) was added and the mixture was extracted with ethyl acetate. The extract was washed with water, dried (MgSO 4 ), evaporated and passed down a silica gel column eluted with ethyl acetate:hexane (1: 1, v/v). The appropriate fractions were evaporated to a solid, which crystallised from ethyl acetate/hexane (0.12g). Mass spectrum: m/e 456 (M+H) M.p.: 68-69°C C 25 H 29 NO 3 S 2 requires: C 65.9 H 6.4 N 3.1 S 14.1 % found: C 65.9 H 6.5 N 3.2 S 14.4 % EXAMPLE 4 6-Methoxy-2-r2-r4-(5-phenylpentylthio)phenoxy1-l-oxoethvnbenzothiazole a) 6-Methoxybenzothiazole 6-Hydroxybenzothiazole (0.246g) was dissolved in dry DMF (20 ml) and treated with sodium hydride (60% oil suspension, 0.072g). The mixture was stirred at 25°C for 10 min, treated with methyl iodide (0.23g) and stirring continued for 18 hrs. The reaction mixture was poured into 2N hydrochloric acid (100 ml) and extracted with ethyl acetate. The extract was washed with water, brine, dried (MgSO ) and evaporated to give the product as an oil, (0.25g). Η NMR, CDC1 3 , d: 3.90 (s, 3H), 7.11-7.15 (dd, 1H), 7.40 (d, 1H), 8.01 (d, 1H), 8.83 (s, 1H). b) 6-Methoxy-2-r2-(4-(5-phenylpentylthio)phenoxy)-l-oxoethvnbenzothiazole Using the procedure described for example 2b but using 6-methoxy-benzothiazole (4a) in place of 1-methylbenzimidazole led to the preparation of the required compound as a white solid in 48% yield. Mass spectrum: m/e 478 (M+H) M.p.: 84-86°C C 27 H 27 NO 3 S 2 requires: C 67.9 H 5.3 N 2.9 S 13.4 % found: C 67.6 H 5.6 N 3.0 S 12.9 % EXAMPLE 5 l-Methyl-2-r2-(4-(5-phenylpentylthio)phenoxy)-l-oxoethyl1imidazole a) (l.l-Dimethyl)ethyl 2-r4-(phenylpentylthio)phenoxy1acetate Using the procedure described for example 2a but using (l,l-dimethyl)ethyl 2- bromoacetate in place of ethyl 2-bromoacetate gave the required product as a colourless oil in quantitative yield. Η NMR, CDC1 3 , d: 1.48 (s, 9H), 1.38-1.51 (m, 2H), 1.56-1.66 (m, 4H), 2.59 (t, 2H), 2.81 (t, 2H), 4.49 (5, 2H), 6.80-6.85 (d, 2H), 7.15-7.20 (m, 3H), 7.24-7.28 (m, 2H), 7.29-7.33 (d, 2H). b) 2-f4-(Phenylpentylthio)phenoxyTacetic acid The ester prepared in example 5a (5.33g) was dissolved in a mixture of formic acid (20 ml) and dichloromethane (80 ml) and stirred at 25°C for 24 hrs. The dichloromethane was evaporated under reduced pressure and the residue treated with water (30 ml). A white precipitate formed which was collected by filtration, washed with water and dried in a vacuum desiccator to give the product as a white solid (4.08g). Η NMR, CDC1 3 , d: 1.38-1.48 (m, 2H), 1.49-1.67 (m, 4H), 2.56-2.62 (t, 2H), 2.80-2.85 (s, 2H), 4.66 (t, 2H), 6.83-6.88 (dd, 2H), 7.14-7.20 (m, 3H), 7.25-7.30 (m, 2H), 7.30-7.35 (d, 2H). c) N-r2-(4-(5-Phenylpentylthio)phenoxy)-l-oxoethyl1pyrrolidine 2-[4-(Phenylpentylthio)phenoxy]acetic acid (4.08g) was dissolved in THF (50 ml) and cooled to 0°C. l,l '-carbonyldiimidazole (2.20g) was added and the solution stirred at 0°C for 1.5 hrs. Pyrrolidine (0.97g) in THF (10 ml) was added dropwise while keeping the reaction temperature below 5°C. The ice-bath was then removed and the reaction was stirred at 25°C for 1.5 hrs. Ethyl acetate (200 ml) was added and the mixture was washed with 2N hydrochloric acid, water, saturated sodium bicarbonate, brine, dried (MgSO 4 ) and evaporated to a gum. The gum was passed down a silica gel column eluted with ethyl acetate :hexane (4: 1, v/v) to afford the product as a colourless oil (4.06g, 86%). Mass spectrum: m e 384 (M+H) C 23 H 29 NO 2 S requires: C 72.0 H 7.6 N 3.7 S 8.3 % found: C 71.7 H 7.6 N 3.7 S 8.2 % d) l-Methyl-2-r2-(4-(5-phenylpentylthio)phenoχy)-l-oxoethvnimidazole A stirred solution of 1-methylimidazole (0.12g) in dry THF (10 ml) was cooled to -78°C under a nitrogen atmosphere. Butyl lithium (1.6M in hexane, 0.93 ml) was added dropwise and the solution stirred at below -60°C for 15 mins. The amide prepared in 5c, (0.515g) in THF (10 ml) was added dropwise over 5 mins, keeping the temperature below -60°C. The reaction was allowed to attain ambient temperature and stirred at 25°C for 0.5 hr. Diethyl ether (20 ml) and 2N hydrochloric acid (50 ml) were added and the two layers separated. The aqueous layer was extracted with ether (2 x 30 ml) and the combined ether extract was washed with water, dried (MgSO 4 ) and evaporated to a colourless oil which solidified on standing (0.46g). The solid re-crystallised from ethyl acetate/hexane. Mass spectrum: m/e 395 (M+H) M.p.: 76-77°C C 23 H 26 N 2 O 2 S requires: C 70.0 H 6.6 N 7.1 S 8.1 % found: C 69.7 H 6.7 N 7.0 S 7.8 % EXAMPLE 6 2-r2-(4-(5-Phenylpentylthio)phenoxy)-l-oxoethvnbenzothiazole Using the procedure described for example 5d but using benzothiazole in place of 1- methylimidazole led to the preparation of the required compound as a white solid in 43% yield. Mass spectrum: m/e 448 (M+H) M.p.: 91-92°C C 26 H 25 NO 2 S2 requires: C 69.8 H 5.6 N 3.1 S 14.3 % found: C 69.6 H 5.7 N 3.3 S 14.3 % EXAMPLE 7 2-f2-(4-(5-Phenylpentylthio)phenoxy)-l-oxoethvnthiazole Using the procedure described for example 5d but using 2-bromothiazole in place of 1- methylimidazole led to the preparation of the required compound as a white solid in 34% yield. Mass spectrum: m/e 398 (M+H) M.p.: 74-75°C C 22 H 23 NO 2 S 2 requires: C 66.5 H 5.8 N 3.5 S 16.1 % found: C 66.8 H 5.9 N 3.7 S 16.0 % EXAMPLE 8 2-r2-(4-(5-Phenylpentylthio)phenoxy)-l-oxoethvnbenzothiazole-6-carboxylic acid Benzothiazole-6-carboxylic acid (0.483g) was dissolved in dry THF (30 ml) and cooled to -78°C under a nitrogen atmosphere. A 1.6 M solution of butyl lithium in hexane (3.7 ml) was added dropwise and the reaction mixture was stirred at -70°C for 0.5 hr. A solution of the amide prepared in example 5c, (0.517g) in dry THF (10 ml) was added dropwise and the reaction was stirred for a further 0.75 hr. The cooling bath was removed, the reaction was allowed to warm to 0°C and treated with a saturated aqueous solution of ammonium chloride (50 ml). The mixture was extracted with ethyl acetate and the extract was washed with water, brine, dried (MgSO ) and evaporated to give the crude product as a solid. This was passed down a silica gel column eluted with hexane:ethyl acetate (1 : 1, v/v) to give the product as a yellow solid, (0.15g). Mass spectrum: m/e 492 (M+l) M.p.: 107-171°C C 27 H 25 NO 4 S requires: C 66.0; H 5.1 ; N 2.9; SI 3.0% found: C 66.2; H 5.2; N 3.0; S 12.9 % EXAMPLE 9 4-Methyl-2-r2-(4-(5-phenylpentylthio)phenoxy)-l-oxoethynthiazole-5-carboxylic acid a) Ethyl 2-bromo-4-methylthiazole-5-carboxylate A solution of (l,l-dimethyl)ethane-2-nitrite (2.5 ml) in acetonitrile (100 ml) was cooled in an ice-bath and treated with the dropwise addition of trimethylsilyl bromide (2.8 ml). After addition was complete the mixture was stirred at 0°C for 20 mins. Ethyl 2-amino-4- methylthiazole-5-carboxylate (2.0 g), dissolved in a mixture of acetonitrile (75 ml) and ethyl acetate (25 ml), was added dropwise, over 40 min while maintaining the temperature at 0°C. The cooling bath was removed and the mixture was stirred at 25°C for 18 hrs. The solvent was removed under reduced pressure and the residue was passed down a silica gel column eluted with ethyl acetate:hexane (2: 1) to afford the product as an orange-red oil (1.88g). Mass spectrum: m/e 250 / 252 (M+l) Η NMR, CDC1 3 , d: 1.36 (t, 3H), 2.71 (s, 3H), 4.33 (q, 2H). b) 2-Bromo-4-methylthiazole-5-carboxyIic acid The thiazole prepared in 9a (1.88g,) was dissolved in a mixture of THF (40 ml) and water (10 ml). Lithium hydroxide monohydrate (1.58g,) was added and the mixture was stirred at 25°C for 18hrs. The reaction mixture was then poured into 2N hydrochloric acid and extracted with ethyl acetate. The extract was washed with water, brine, dried (MgSO 4 ) and evaporated to afford the product as a white solid, (1.64g). Mass spectrum: m/e 293 / 295 (TMS -ester) Η NMR, DMSOl D 6 , d: 2.60 (s, 3H). c) 4-Methyl-2-r2-(4-(5-phenylpentylthio)phenoxy)-l-oxoethyllthiazole-5-carboxylic acid Using the procedure described for example 8 but using 2-bromo-4-methyl-thiazole-5- carboxylic acid in place of benzothiazole-6-carboxylic acid led to the preparation of the required compound as a white solid in 71% yield. Mass spectrum: m/e 456 (M+l) M.p.: 142-3°C C 24 H 25 NO 4 S 2 requires: C 63.3 H 5.5 N 3.1 S 14.1 % found: C 63.0 H 5.4 N 3.2 S 13.8 % EXAMPLE 10 4.[2-(2-(4-(5-Phenylpentylthio)phenoxy)-l-oxoethyl)-4-methylthiazol-5-yllbutanoic acid a) Methyl 5-bromo-6-oxo-heptanoate Methyl 6-oxo-heptanoate (5.22g) in dry acetonitrile (50 ml) was treated with slow addition of TMSBr (5.05g) followed by slow addition of DMSO (2.58g). During the additions the reaction temperature was kept below 20°C by cooling in an ice-bath. The mixture was then stirred at ambient temperature for 18 hrs, poured into water and extracted with ether. The ether extract was washed with water, brine, dried (MgSO 4 ) and evaporated to an oil which was purified by a silica gel column eluted with hexane:ethyl acetate (5: 1, v/v). The appropriate fractions were evaporated to afford the product as a clear oil (4.0g). Mass spectrum : m/e 236 / 238 1H NMR, CDC1 3 , d: 1.6-2.2 (m, 4H), 2.36 (s, 3H,), 2.38(t, 2H), 3.7 (s, 3H) 4.24 (dd, 1H). b) Methyl 4-(2-amino-4-methylthiazol-5-yl)butanoate hvdrobromide Methyl 5-bromo-6-oxoheptanoate (1.16g) was dissolved in ethanol (50 ml) and treated with thiourea (0.373g).The mixture was heated at reflux for 4 hrs and the solvent was removed under reduced pressure to give the product as a white solid ( 1.44g). Mass spectrum : m/e 214 Η NMR, CDC1 3 , d: 1.81 - 1.91 (m, 2H), 2.20 (s, 3H), 2.36 (t, 2H), 2.60 (t, 2H), 3.69 (s, 3H), 8.80 (bs, 3H). c) Methyl 4-(2-bromo-4-methylthiazol-5-yl)butanoate Using the procedure described in 9a, with the 2-aminothiazole derivative prepared in 10b, led to the required product as an orange-red oil in 33% yield. Mass spectrum : m/e 277 / 279 1H NMR, CDC1 3 , d: 1 1..81 7-1.98 (m, 2H), 2.31 (s, 3H), 2.36 (t, 2H), 2.75 (t, 2H), 3.67 (s, 3H). d) 4-(2-Bromo-4-methylthiazol-5-yl)butanoic acid Using the procedure described in 9b, with the 2-bromothiazole derivative prepared in 10c, led to the required product as a white solid in 73% yield. Mass spectrum : m e 264 / 266 (M+l) 1H NMR, CDC1 3 , d: 1.88- 1.98 (m, 2H), 2.32 (s, 3H), 2.42 (t, 2H), 2.78 (t, 2H). e) 4-r2-(2-(4-(5-Phenylpentylthio)phenoχy)-l-oxoethyl)-4-methylthiazol-5-yllbutanoic acid Using the procedure described for example 8 but using 4-(2-bromo-4-methylthiazol-5- yl)butanoic acid in place of benzothiazole-6-carboxylic acid led to the preparation of the required compound as a white solid in 33% yield. Mass spectrum: τn/e 498 (M+ 1 ) M.p.: 97-98°C C 27 H 31 NO 4 S 2 requires: C 65.2 H 6.3 N 2.8 S 12.9 % found: C 65.2 H 6.4 N 2.8 S 12.7 % EXAMPLE 11 2-r2-(4-(3,5-DichlorobenzvIoxy)phenoxy)-l-oxoethvπthiazole a) 4-r3,5-Dichlorobenzyloxylphenol Quinol (4.9g) was dissolved in dry DMF (100 ml) and treated with caesium carbonate (14.6g). 3,5-Dichlorobenzylchloride (2.9g) was added and the mixture was stirred at 25°C for 72 hrs. The mixture was poured into 2N hydrochloric acid (250 ml) and extracted with ethyl acetate. The extract was washed with water, brine, dried (MgSO 4 ), evaporated and the residue passed down a silica gel column eluted with hexane:ethyl acetate (5:1, v/v). The appropriate fractions were combined and evaporated to give the product as a white solid, (2.41g). Mass spectrum : m/e 268 / 270 / 272 Η NMR, CDC1 3 , d: 4.55 (s, 1H), 4.95 (s, 2H), 6.75-6.85 (m, 4H) 7.31 (s, 3H). b) Ethyl 2-r4-(3.5-dichlorobenzyloxy)phenoxy]acetate The procedure described in example 2a was used with ethyl 2-bromoacetate and 4-(3,5- dichlorobenzyloxy)phenol to give the product as a white solid in 98% yield. Mass spectrum : m e 354 / 356 / 358 Η NMR, CDC1 3 , d: 1.30 (t, 3H), 4.3 (q, 2H), 4.58 (s, 2H), 4.96 (s, 2H) 6.89 (s, 4H), 7.31 (s, 3H). c) 2-r2-(4-(3.5-Pichlorobenzyloxy)phenoxy)-l-oxoethvnthiazole The procedure described in example 2b was used with 2-bromothiazole and ethyl 2-[4- (3, 5-dichlorobenzyloxy)phenoxy] acetate to give the product as a white solid in 32% yield. Mass spectrum: m/e 394 / 396 / 398 (M+l) M.p.: 116-118°C Ci 8 H 13 Cl 2 NO 3 S requires: C 54.8 H 3.3 N 3.6 S 8.1 % found: C 54.9 H 3.3 N 3.8 S 7.9 % EXAMPLE 12 5-(2-Hydroxyethyl)-4-methyl-2-r2-(4-(3,5-dichlorobenzyloxy)phenoxy)-l- oxoethyllthiazole a) 5-(2-(Di ethyl(lJ-dimethylethyl)silyloxy)ethyl)-4-methyl-2-r2-(4-(3.5- dichlorobenzyloxy)phenoxy)-l-oxoethyl1thiazole The procedure described in example 2b was used with the thiazole prepared in 3 a and ethyl 2-[4-(3,5-dichlorobenzyloxy)phenoxy]acetate to give the product as a yellow gum in 32% yield. Mass spectrum: m/e 566 / 568 / 570 (M+l) 1H NMR, CDC1 3 , d: 0.02 (s, 6H), 0.88 (s, 9H), 2.44 (s, 3H), 3.02 (t, 2H), 3.82 (t, 2H), 4.95 (s, 2H), 5.43 (s, 2H), 6.8-7.0 (m, 4H), 7.31 (s, 3H). b) 5-(2-Hvdroxyethyl)-4-methyl-2-r2-(4-(3,5-dichlorobenzyloχy)phenoxy)-l- oxoethyll thiazole The product from 12a (0.36g) was dissolved in ethanol (10 ml), treated with pyridinium p- toluenesulfonate (0.08g) and water (0.25 ml) and the reaction was heated at 60°C for 8 hrs. The solvent was evaporated under reduced pressure and the residue was dissolved in ethyl acetate (100 ml), washed with water, brine, dried (MgSO 4 ) and evaporated. The residue was purified by passing down a silica gel column eluted with ethyl acetate:hexane (1:1, v/v) to give the product as a white solid which crystallised from ethyl acetate/hexane (0.18g). Mass spectrum: m/e 452 / 454 / 456 (M+l) M.p.: 115-116°C 1H NMR, CDC1 3 , d: 1.64 (bs, 1H), 2.45 (s, 3H), 3.08 (t, 2H), 3.91 (m, 2H), 4.96 (s, 2H), 5.43 (s, 2H), 6.8-7.0 (m, 4H), 7.31 (s, 3H). EXAMPLE 13 5-(2-Hvdroxyethyl)-4-nιethvI-2-r2-(4-(decylsulfonyl)phenoxy)-l-oxoethyllthiazole a) 4-(Decylthio)phenol A solution of decyl bromide (11.5 ml) and 4-hydroxythiophenol (7g) in acetonitrile (100 ml) was treated with caesium carbonate (18g) and stirred at 25°C for 18 hrs. The reaction was poured into 2N hydrochloric acid (500 ml) and the product was extracted into ethyl acetate. The extract was washed with water, brine, dried (MgSO ) and evaporated under reduced pressure to give the product as a solid (12.5g). Mass spectrum: m/e 266 M.p.: 81-82°C C 16 H 26 OS requires: C 72.1 H 9.8 N 12.0 % found: C 72.2 H 9.9 N 12.1 % b 4-(PecylsuIfonyl phenol 4-(Decylthio)phenol (5.3 lg) was dissolved in acetone (500 ml). Water (100 ml) was added and the solution was cooled in an ice-bath. Oxone (15g) was added, the ice-bath was removed and the mixture was stirred at 25°C for 18 hrs. A 10% aqueous solution of sodium metabisulphite (1 It) was added and the mixture was stirred for a further lhr. The mixture was extracted with ethyl acetate and the extract was washed with water, brine, dried (MgSO 4 ) and evaporated to give a clear oil, (5.65g). Mass spectrum: m/e 297 (M-l) 1H NMR, CDC1 3 , d: 0.87 (t, 3H), 1.2-1.3 (m, 12H), 1.35 (m, 2H), 1.67 (m, 2H), 3.06 (m, 2H), 6.56 (bs, 1H), 6.96 (d, 2H), 7.75 (d, 2H). c) Ethyl 2-f 4-(decylsulf on vDphenoxyl acetate The procedure described in example 2a was used with ethyl 2-bromoacetate and 4- (decylsulfonyl)phenol to give the required product as a white solid in 78% yield. Mass spectrum : m/e 385 (M+l) 1H NMR, CDC1 3 , d: 0.87 (t, 3H), 1.23 (m, 14H), 1.31 (t, 3H), 1.64-1.74 (m, 2H), 3.02-3.07 (m, 2H), 4.29 (q, 2H), 4.70 (s, 2H), 7.00-7.04 (d, 2H), 7.82-7.86 (d, 2H). d) 5-(2-(Dimethyl(l.l-dimethylethvnsilyloxy)ethyl)-4-methyl-2-r2-(4- (decylsulfonyl)phenoxy)-l-oxoethyl1thiazole The procedure described in example 2b was used with the thiazole prepared in 3a and ethyl 2-[4-(decylsulfonyl)phenoxy]acetate to give the product as a colourless gum in 20% yield. Η NMR, CDC1 3 , d: 0.02 (s, 6H), 0.87 (s, 12H), 1.2-1.3 (m, 12H), 1.35 (m, 2H), 1.69 (m, 2H), 2.46 (s, 3H), 3.05 (m, 4H), 3.84 (t, 2H), 5.57 (s, 2H), 7.07 (d, 2H), 7.83 (d, 2H). e) 5-(2-Hvdroxyethyl)-4-methyl-2-r2-(4-(decylsulfonyl)phenoxy)-l-oxoethvnthiazole The procedure described in example 12b was used with the product of 13d to give the product as white solid, which analysed as a monohydrate. Mass spectrum: m/e 482 (M+l) M.p.: 53-55°C C 24 H 35 NO 5 S 2 .H 2 O requires: C 57.7 H 7.5 N 2.8 S 12.8 % found: C 57.9 H 7.4 N 2.8 S 12.7 % EXAMPLE 14 5-(2-Hvdroxyethyl)-4-methyl-2-r2-(4-(benzyloxy)phenoxy)-l-oxoethvnthiazoIe a) Ethyl 2-r4-(benzyloχy)phenoxy1acetate The procedure described in example 2a was used with ethyl 2-bromoacetate and 4- (benzyloxy)phenol to give the required product as a white solid in 78% yield. Mass spectrum : m/e 286 1H NMR, CDC1 3 , d: 1.29 (t, 3H), 4.26 (q, 2H)), 4.56 (s, 2H), 5.01 (s, 2H)., 6.84- 6.92 (m, 4H), 7.29-7.44 (m, 5H). b) 5-(2-(Dimethyl(Ll-dimethylethyl)silyloxy)ethyl)-4-methyl-2-r2-(4- (benzyloxy)phenoxy)-l-oxoethyllthiazole The procedure described in example 2b was used with the thiazole prepared in 3 a and ethyl 2- [4-(benzyloxy)phenoxy] acetate to give the product as a pale yellow gum in 67% yield. 1H NMR, CDC1 3 , d: 0.02 (s, 6H), 0.87 (s, 9H), 2.44 (s, 3H), 3.01 (t, 2H), 3.82 (t, 2H), 5.01 (s, 2H), 5.42 (s, 2H), 6.8-7.0 (m, 4H), 7.3-7.5 (m, 5H). c) 5-(2-Hvdroxyethyl)-4-methyl-2-r2-(4-(benzyloxy)phenoxy)-l-oxoethyllthiazole The procedure described in example 12b was used with the product of 14b to give the product as white solid in 64% yield. Mass spectrum: m e 384 (M+l) M.p.: 109-110°C C 21 H 21 NO 4 S requires: C 65.8 H 5.5 N 3.7 S 8.4 % found: C 66.2 H 5.6 N 3.8 S 8.4 % EXAMPLE 15 5-(2-Hvdroxyethyl)-4-methyl-2-r2-(4-(benzylthio)phenoxy)-l-oxoethyllthiazole a) 4-(Benzylthio)phenol The procedure described in example 13a was used with 4-hydroxythiophenol and benzyl chloride to give the required product as a white solid in 48% yield. Mass spectrum : m/e 215 (M-l) 1HNMR, CDC1 3 , d: 3.97 (s, 2H), 4.92 (s, 1H), 6.73 (d, 2H), 7.25 (m, 7H). b) Ethyl 2-f4-(benzylthio)phenoxy1acetate The procedure described in example 2a was used with ethyl 2-bromoacetate and 4- (benzylthio)phenol to give the required product as a white solid in 90% yield. Mass spectrum : m/e 302 (M+) Η NMR, CDC1 3 , d: 1.29 (t, 3H), 3.99 (s, 2H), 4.26 (q, 2H), 4.58 (s, 2H), 6.8 (d, 2H), 7.25 (m, 7H). c) 5-(2-(Dimethyl(l.l-dimethylethyl)silvIoxy ethyl)-4-methyl-2-r2-(4- (benzvIthio)phenoxy)-l-oxoethvHthiazole The procedure described in example 2b was used with the thiazole prepared in 3a and ethyl 2-[4-(benzylthio)phenoxy]acetate to give the product as an yellow-orange gum 95% yield. Mass spectrum : m/e 514 (M+) Η NMR, CDC1 3 , d: 0.05 (s, 6H), 0.88 (s, 9H), 2.45 (s, 3H), 3.0 (t, 2H), 3.83 (t, 2H), 3.99 (s, 2H), 5.44 (s, 2H), 6.88 (d, 2H), 7.27 (m, 7H). d) 5-(2-Hvdroxyethyl)-4-methyl-2-r2-(4-(benzylthio)phenoxy)-l-oxoethyl)thiazole The procedure described in example 12b was used with the product of 15c to give the product as white solid in 45% yield. Mass spectrum: m/e 400 (M+l) M.p.: 103-4°C C 21 H 21 NO 3 S 2 requires: C 63.1 H 5.3 N 3.5 S 16.1 % found: C 62.8 H 5.2 N 3.6 S 16.2% EXAMPLE 16 5-(2-Hvdroxyethyl)-4-methyl-2-f2-(4-(3,5-dichlorobenzylthio)phenoxy)-l- oxoethyllthiazole a) 4-r3,5-Dichloro(benzylthio)1phenol The procedure described in example 13a was used with 4-thiophenol and 3,5- dichlorobenzylchloride to give the required product as a colourless oil in 97% yield. Mass spectrum : m/e 283 / 285 / 287 (M-l) l H NMR, CDC1 3 , d: 2.05 (s, 1H), 3.86 (s, 2H), 6.75 (d, 2H), 6.91 (d, 2H), 7.20 (m, 3H). b Ethyl 2-r4-(3,5-dichlorobenzylthio)phenoxylacetate The procedure described in example 2a was used with ethyl 2-bromoacetate and 4-[3,5- Dichloro(benzylthio)]phenol to give the required product as a colourless oil in 78% yield. Mass spectrum : m/e 370 / 372 / 374 (M+) 1H NMR, CDC1 3 , d: 1.29 (t, 3H), 3.88 (s, 2H), 4.27 (q, 2H), 4.59 (s, 2H), 6.82 (d, 2H), 7.03 (d, 2H), 7.22 (m, 3H). c) 5-(2-(Dimethyl(l.l-dimethylethyl)silyloχy)ethyl)-4-methyl-2-r2-(4-(3.5- dichlorobenzylthio)phenoxy)-l-oxoethvnthiazole The procedure described in example 2b was used with the thiazole prepared in 3a and ethyl 2-[4-(3,5-dicholrobenzylthio)phenoxy]acetate to give the product as a pale yellow oil in 99% yield. Mass spectrum : m/e 582 / 584 / 586 (M+l) Η NMR, CDC1 3 , d: 0.04 (s, 6H), 0.88 (s, 9H), 2.45 (s, 3H), 3.02 (t, 2H), 3.82 (t, 2H), 3.88 (s, 2H), 5.46 (s, 2H), 6.9 (d, 2H), 7.25 (m, 7H). d) 5-(2-Hvdroxyethyl)-4-methyl-2-r2-(4-(3,5-dichlorobenzylthio)phenoxy)-l- oxoethvDthiazole The procedure described in example 12b was used with the product of 16c to give the product as white solid in 57% yield. This analysed as the hemi-hydrade. Mass spectrum: m/e 468 / 470 / 472 (M+ 1 ) M.p.: 99-100°C C 2 iH I9 Cl 2 NO 3 S 2 • 1 / 2 H 2 O requires: C 52.8 H 4.1 N 2.9 S 13.4% found: C 52.9 H 4.0 N 2.9 S 13.0 % EXAMPLE 17 l-Methyl-2-r2-(4-(5-phenylpentylsulfonyl)phenoxy)-l-oxoethyllbenzimidazole 1 -Methyl-2-[2-(4-(5-phenylpentylthio)phenoxy)- 1 -oxoethyljbenzimidazole (0.075g) was dissolved in a mixture of acetone (5 ml) and water (1 ml). Oxone (0.15g) was added and the mixture was stirred at 25°C for 18 hrs. A 10% aqueous solution of sodium thiosulphate (50 ml) was added and the mixture was stirred for a further 0.5 hr. The mixture was extracted with ethyl acetate and the extract was washed with 10% sodium thiosulphate solution, water, brine, dried (MgSO ) and evaporated to give a white solid (0.058g) which recrystallised from acetonitrile. Mass spectrum: m/e 477 (M+l) M.p.: 149-150 °C Η NMR, CDC1 3 , d: 1.4 (m, 2H), 1.5-1.8 (m, 4H), 2.58 (t, 2H), 3.04 (m, 2H), 4.18 (s, 3H), 5.77 (s, 2H), 7.1-7.3 (m, 7H), 7.4-7.6 (m, 3H), 7.8-8.0 (m, 3H). EXAMPLE 18 2-r2-(4-(5-Phenylpentylsulfonyl)phenoxy)-l-oxoethvnbenzothiazole The procedure described in example 17 was used with 2-[2-(4- (phenylpentylthio)phenoxy)-l-oxoethyl]benzothiazole to give the product as a white solid in 65% yield. Mass spectrum: m/e 480 (M+l) M.p.: 127-8°C C 27 H 28 N 2 O 4 S requires: C 65.1 H 5.3 N 2.9 S 13.4 % found: C 64.9 H 5.1 N 2.9 S 13.0 % EXAMPLE 19 2-f2-(4-(5-PhenylpentylsulfonvI)phenoxy)-l-oxoethyll-6-methoxybenzothiazole The procedure described in example 17 was used with 2-[2-(4- (phenylpentylthio)phenoxy)-l-oxoethyl]-6-methoxybenzothiazole to give the product as a solid in 60% yield. Mass spectrum: m/e 510 (M+l) M.p.: 109-110°C C 26 H 2 5NO4S 2 requires: C 63.6 H 5.3 N 2.8 S 12.6 % found: C 64.6 H 5.5 N 2.9 S 12.7 % EXAMPLE 20 5-(2-Hvdroxyethyl)-4-methyl-2-r2-(4-(3.5-dichlorobenzylsulfonyl)phenoxy)-l- oxoethyllthiazole The procedure described in example 17 was used with 5-(2-hydroxyethyl)-4-methyl-2-[2- (4-(3,5-dichlorobenzylthio)phenoxy)-l-oxoethyl]thiazole to give the product as a solid in 69% yield. Mass spectrum: m/e 500 / 502 / 504 (M+ 1 ) M.p.: 116-7°C C 2 iH 19 Cl 2 NO 5 S 2 requires: C 50.4 H 3.8 N 2.8 S 12.8 % found: C 49.9 H 3.7 N 2.7 S 13.2% EXAMPLE 21 2-r2-(4-(3.4-Dichlorobenzylthio)phenoxy)-l-oxoethvnbenzoxazole a) 4-(3.4-DichlorobenzvIthio)phenol The procedure described in example 13a was used with 4-thiophenol and 3,4- dichlorobenzylchloride to give the required product as a yellow solid in quantitative yield. Mass spectrum: m/e 283 / 285 / 287 NMR: CDC1 3 d: 3.87 (s, 2H), 4.91 (s, 1H), 6.74 (d, 2H), 6.96 (dd, 1H), 7.19 (d, 2H), 7.2-7.5 (m, 2H). b) 2-r4-(3.4-Dichlorobenzylthio)phenoxylacetonitrile The procedure described in example le was used with 2-bromoacetonitrile and 4-(3,4- dichlorobenzylthio)phenol to give the required product as a yellow oil in 71% yield. Mass spectrum: m/e 323 / 325 / 327 NMR: CDCI 3 d: 3.94 (s, 2H), 4.76 (s, 2H), 6.90 (d, 2H), 7.02 (d, 1H), 7.27-7.35 (m, 4H). c) 2-r4-(3.4-Dichlorobenzylthio)phenoxy1acetaldehvde The procedure described in example If was used with the product of 21b to give the required product as a colourless oil in 50% yield. This was used directly in the next step. NMR: CDCI 3 d: 3.90 (s, 2H), 4.56 (s, 2H), 7.2-7.35 (m, 7H), 9.85 (s, 1H). d) 3-r4-(3,4-Dichlorobenzylthio)phenoxy1-2-hvdroχypropionitrile The procedure described in example lg was used with the product from 21c to give the required product as a colourless oil in 74% yield. NMR: CDC1 3 d: 3.04 (d, IH), 3.91 (s, 2H), 4.4-4.5 (m,2H), 4.82 (m, IH), 6.84 (d, 2H), 6.99 (dd, IH), 7.23-7.28 (m, 3H), 7.32 (d, IH). e) 3-f4-(3 < 4-Dichlorobenzylthio)phenoxy]-2-hydroxy-l-ethoxy-l-iminopropane hvdrochloride The procedure described in example lh was used with the product from 2 Id to give the required product as a white solid in 93% yield. This was used directly in the next step. NMR: DMSO D6 d: 1.29 (t, 3H), 4.12 (s, 2H), 4.21 (d, 2H), 4.47(m, 2H), 4.81 (s, IH), 6.88 (d, 2H), 7.2-7.3 (m,3H), 7.46 (d, IH), 7.53 (d, IH). f) 2-r2-(4-(3.4-Dichlorobenzylthio)phenoxy)-l-hydroxyethvnbenzoxazole The procedure described in example li was used with the product from 21e and 2- aminophenol to give the required product as a yellow solid in 64% yield. Mass spectrum: m/e 446 / 448 / 450 (M+l) NMR: CDCI 3 d: 3.41 (d, IH), 3.88 (s, 2H), 4.47 (m, 2H), 5.35 (m, IH), 6.84 (d, 2H), 6.94 (dd, IH), 7.18-7.32 (m, 6H), 7.75 (m, IH), 8.57 (m, IH). g) 2-r2-(4-(3.4-Dichlorobenzylthio)phenoxy)-l-oxoethvn benzoxazole The procedure described in example lj was used with the product from 21h to give the required product as a yellow solid in 80% yield. Mass spectrum: m/e 444 / 446 / 448 (M+l ) M.p.: 122-123°C C 22 H 15 CI2NO 3 S requires: C 59.5 H 3.4 N 3.2 S 7.2 % found: C 59.4 H 3.4 N 3.4 S 7.4 % EXAMPLE 22 2-f2-(4-(3,4-Dichlorobenzylthio)phenoxy)-l-oxoethvn benzimidazole a) 2-r2-(4-(3.4-Dichlorobenzylthio)phenoxy)-l-hvdroxyethyl1benzimidazole The procedure described in example li was used with the product from 21e and 2,3- diaminobenzene to give the required product as a yellow solid in 65% yield. Mass spectrum: m/e 445 / 447 / 449 (M+ 1 ) NMR: CDC1 3 d: 3.89 (s, 2H), 4.26 (dd, IH), 4.57 (dd, IH), 5.42 (q, IH), 6.88 (d, 2H), 6.97 (dd, IH), 7.20-7.31 (m, 8H), 7.61 (m, 2H). b) 2-r2-(4-(3.4-Dichlorobenzylthio)phenoxy)-l-oxoethyllbenzimidazole The procedure described in example lj was used with the product from 22a to give the required product as a white solid in 56% yield which analysed as a hemihydrate. Mass spectrum : m/e 443 / 445 / 447 (M+l) M.p.: 141-142°C C 22 H 16 CI2N2O 2 S • 0.5H 2 O requires: C 58.4 H 3.8 N 6.2 S 7.1 % found: C 58.8 H 3.7 N 6.2 S 7.1 % EXAMPLE 23 2-r2-(4-(3.4-Dichlorobenzylthio)phenoxy)-l-oxoethyll-6-methoxy benzoxazole a) 2-f2-(4-(3.4-Dichlorobenzylthio)phenoxy)-l-hvdroxyethvn-6-methoxybenzoxazole The procedure described in example li was used with the product from 21e and 2-amino- 5-methoxyphenol to give the required product as a yellow solid in 57% yield. Mass spectrum: m/e 476 / 478 / 480 (M+l) M.p.: 87-88°C C 2 3H 19 NCI 2 O 4 S requires: C 58.0 H 4.0 N 2.9 S 6.7 % found: C 58.1 H 4.0 N 3.0 S 6.9 % b) 2-r2-(4-(3,4-Dichlorobenzylthio phenoxy)-l-oxoethyl]-6-methoxybenzoxazoIe The procedure described in example lj was used with the product from 23 a to give the required product as a yellow solid in 84% yield. Mass spectrum: m/e 474 / 476 / 478 (M+l ) M.p.: 136-137 °C C 23 H 17 NCl 2 O 4 S requires: C 58.2 H 3.6 N 3.0 S 6.8 % found: C 57.9 H 3.6 N 3.2 S 6.7 % EXAMPLE 24 2-r2-(4-(3 > 4-Dichlorobenzylthio)phenoxy)-l-oxoethvnbenzoxazole-5-carboxylic acid a) (l -Dimethyl ethyl 2-r2-(4-(3.4-dichlorobenzylthio)phenoxy)-l- hydroxyethyllbenzoxazole-5-carboxylate. The procedure described in example li was used with the product from 21e and product from lb to give the required product as a yellow solid in 61% yield. NMR: CDC1 3 d: 1.62 (s, 9H), 3.32 (d, IH), 3.88 (s, 2H) 4.49 (m, 2H), 5.36 (m, IH), 6.84 (d, 2H), 6.97 (dd, IH), 7.2-7.31 (m, 4H), 7.56 (d, IH), 8.08 (dd, IH), 8.39 (d, IH). b) (l.l-Dimethvnethyl 2-r2-(4-(3.4-dichlorobenzylthio)phenoxy)-l- oxoethvHbenzoxazole-5-carboxylate. The procedure described in example lj was used with the product from 24a to give the required product as a yellow solid in 66% yield. NMR: CDCI 3 d: 1.60 (s, 9H), 3.91 (s, 2H), 5.55 (s, 2H), 6.92 (d, 2H), 6.98 (dd, IH), 7.23-7.32 (m, 4H), 7.72 (d, IH), 8.26 (dd, IH), 8.57 (d, IH). c) 2-r2-(4-(3,4-Dichlorobenzylthio)phenoxy)-l -oxoethyllbenzoxazole-5-carboxylic acid The procedure described in example Ik was used with the product from 24b to give the required product as a white solid in 56% yield which analysed as a monohydrate. Mass spectrum: m/e 488 / 490 / 492 (M+l) M.p.: 174-175°C C 23 H 15 NCl 2 O 5 S.H 2 O requires: C 54.6 H 3.4 N 2.8 S 6.3 % found: C 54.2 H 3.2 N 2.9 S 6.1 % EXAMPLE 25 2-r2-(4-(3.4-Dichlorobenzylthio)phenoxy)-l-oxoethyllbenzoxazole-6-carboxylic acid a) Propen-3-yl 3-hvdroxy-4-aminobenzoate 3-Hydroxy-4-aminobenzoic acid (l.Og) was suspended in propen-3-ol (20 ml) and trimethylsilyl chloride (3.3 ml) was added dropwise. The reaction mixture was heated at 65 °C for 18 hrs, the reaction was allowed to cool to room temperature and poured into 2N hydrochloric acid. The mixture was extracted with ethyl acetate and the extract evaporated to give a brown oil. This was passed down a silica gel column eluted with ethyl acetate:hexane (4: 1) to afford the product as a yellow solid (0.62g). l H NMR: CDC1 3 d: 4.20 (bs, 2H), 4.77 (m, 2H), 5.27 (dd, IH), 5.39 (dd, IH), 5.89 (bs, IH), 6.03 (m, IH), 6.68 (d, IH), 7.56 (m, 2H). b) Propen-3-yl 2-r2-(4-(3,4-dichlorobenzylthio)phenoxy)-l -hvdroxyethyllbenzoxazole- 6-carboxylate. The procedure described in example li was used with the product from 21e and the product from 25a to give the required product as a yellow solid in 14% yield. l U NMR: CDCI 3 d: 3.28 (d, IH), 3.88 (s, 2H) 4.49 (m, 2H), 4.87 (d, 2H), 5.3-5.47 (m, 3H), 6.06 (m, IH), 6.84 (d, 2H), 6.97 (dd,lH), 7.2-7.31 (m, 4H), 7.78 (d, IH), 8.14 (dd, IH), 8.28 (s, IH). c Propen-3-yl 2-r2-(4-(3.4-dichlorobenzylthio)phenoxy)-l-oxoethyllbenzoxazole-6- carboxylate. The procedure described in example lj was used with the product from 25b to give the required product as a yellow solid in 56% yield. H NMR: CDC1 3 d: 3.89 (s, 2H), 4.89 (m, 2H), 5.35 (dd, IH), 5.45 (dd, IH), 5.55 (s,2H), 6.07 (m, IH), 6.92 (d, 2H), 6.98 (dd,lH), 7.23-7.28 (m, 3H), 7.31 (d,lH), 7.97 (m, 2H), 8.41 (s, IH). d) 2-r2-(4-(3.4-Dichlorobenzylthio)phenoxy)-l-oxoethvnbenzoxazole-6-carboxylic acid Dry nitrogen was bubbled through dry THF (10 ml) for 0.5hrs. The product from 25c (0.14g) was added followed by tetrakis(triphenylphosphine)palladium (0.02g) and acetic acid (0.3 ml). The reaction was stirred at 25°C, under nitrogen for 2 hrs. The reaction was evaporated and the residue passed down a silica gel column eluted with 5% methanol in dichloromethane to give the product as a pale yellow solid (0.092g). Mass spectrum: m/e 488 / 490 / 492 (M+ 1 ) M.p.: 179-180°C EXAMPLE 26 2-r2-(4-(3.5-Dichlorobenzyloxy)phenoxy)-l-oxoethyllbenzoxazole-5-carboxylic acid a) 2-f4-(3.5-Dichlorobenzyloxy)phenoxy1acetonitrile The procedure described in example le was used with 2-bromoacetonitrile and 4-(3,5- dichlorobenzyk>xy)phenol to give the required product as a yellow oil in 82% yield. H NMR: CDCI 3 d: 4.72 (s, 2H), 4.98 (s, 2H), 6.94 (m, 4H), 7.32 (s, 3H). b) 2-r4-(3,5-Dichlorobenzyloxy)phenoxylacetaldehyde The procedure described in example If was used with the product of 26a to give the required product as a yellow oil in 84% yield. The product was used directly in the next step. c) 3-r4-(3,5-dichlorobenzyloxy)phenoxyl-2-hvdroxypropionitrile The procedure described in example lg was used with the product from 26b to give the required product as a white solid in 78% yield. M.p.: 89-90°C ! H NMR: CDC1 3 d: 3.02 (s, IH), 4.20 (m, 2H), 4.79 (m, IH), 4.97 (s, 2H), 6.90 (s, 4H), 7.31 (s, 3H). d) 3-r4-(3.5-dichlorobenzyloxy)phenoxy1-2-h vdroxy-1 -ethoxy-1 -iminopropane hvdrochloride The procedure described in example lh was used with the product from 26c to give the required product as a white solid in 71% yield. This was used directly in the next step. ! H NMR: DMSO d6 d: 1.30 (t,3H), 4.17 (d, 2H), 4.44 (m, 2H), 4.78 (s, IH), 5.09 (s, 2H), 5.92 (m, 4H), 7.49 (s, 2H), 7.57 (s, IH). e) (l.l-Dimethyl)ethyl 2-r2-(4-(3.5-dichlorobenzyloxy)phenoxy)-l- hvdroxyethyllbenzoxazole-5-carboxylate The procedure described in example li was used with the product from 26d and the product from example lb to give the required product as an orange oil in 93% yield. Mass spectrum: m/e 530 / 532 / 534 (M+l ) ! H NMR: CDCI 3 d: 1.62 (s, 9H), 3.31( d, IH), 4.47 (m, 2H), 4.95 (s, 2H), 5.34 (m, IH), 6.87 (d, 4H), 7.30 (s, 3H), 7.56 (d, IH), 8.07 (dd, IH), 8.39 (d, IH). f) (l.l-Dimethyl)ethyl 2-r2-(4-(3.5-dichlorobenzyloxy)phenoxy)-l- oxoethvπbenzoxazole-5-carboxylate. The procedure described for example lj was used with the product from example 26e to give the product as an off-white solid in 94% yield. Mass spectrum: m/e 528 / 530 / 532 (M+l) J H NMR: CDC1 3 d: 1.64 (s, 9H), 4.97 (s, 2H), 5.52 (s, 2H), 6.94 (q, 4H), 7.31 (s, 3H), 7.71 (d, IH), 8.25 (d, 1H),8.56 (d, IH). g) 2-r2-(4-(3.5-Dichlorobenzyloxy)phenoxy)-l -oxoethvnbenzoxazole-5-carboxylic acid The procedure described in example Ik was used with the product from 26f to give the required product as a white solid in 62% yield. Mass spectrum: m/e 472 / 474 / 476 (M+l) M.p.: 169-170°C C 23 Hι 5 NCl 2 O 6 requires: C 58.4 H 3.2 N 3.0 % found: C 57.5 H 3.0 N 3.0 % EXAMPLE 27 2-r2-(4-(3.5-Dichlorobenzyloxy)phenoxy)-l-oxoethyllbenzimidazole-5-carboxyIic acid a) Propen-3-yl 3.4-diaminobenzoate The procedure described for example 25a was used with 3,4-diaminobenzoic acid to afford the product as a brown solid in 43% yield. *H NMR: CDCI 3 d: 4.77 (m, 2H), 5.26 (dd, IH), 5.35 (dd, IH), 6.02 (m, IH), 6.65 (d, IH), 7.43 (d, IH), 7.51 (dd, IH). b) Propen-3-yl 2-r2-(4-(3,5-dichlorobenzyloxy)phenoxy)-l -hvdroxyethyl]-5- benzimidazole carboxylate. The procedure described in example 1 i was used with the product from 26d and product from 27a to give the required product as a light brown oil in 61% yield. Mass spectrum: m/e 513 / 515 / 517 (M+l) c) Propen-3-yl 2- r 2-(4-(3.5-dichlorobenzyloxy)phenoxy)-l -oxoethyll-5-benzimidazole carboxylate. The procedure described in example lj was used with the product from 27b to give the required product as a yellow solid in 78% yield. Mass spectrum: m/e 51 1 / 513 / 515 (M+l) l H NMR: DMSO D6 d: 4.85 (d, 2H), 5.08 (s, 2H), 5.31-5.46 (m, 2H), 5.66 (s, 2H) 6.09 (m, IH), 6.96 (m, 4H), 7.50 (s, 2H), 7.57 (m, IH), 7.70 (d, IH), 8.02 (dd, IH) 8.230 (d, IH). d) 2-r2-(4-(3.5-DichlorobenzvIoxy)phenoxy)-l-oxoethvnbenzimidazole-6-carboxylic acid The procedure used in example 25d was used with the product from 26c to give the product as a pale yellow solid in 38 % yield, as the hydrate. Mass spectrum: m/e 471 / 473 / 475 (M+ 1 ) M.p.: >300°C C 23 H 16 N 2 CI 2 O 5 .H2O requires: C 56.5 H 3.7 N 5.7 % found: C 56.8 H 3.6 N 5.5 % EXAMPLE 28 3-r2-(2-(4-(3.5-Dichlorobenzyloxy)phenoxy)-l-oxoethyl)benzoxazol-5-vnpropionic acid a) Propen-3-yl 3-(3-hvdroxy-4-aminophenyl)propionate The procedure described for example 25a was used with 3-(3-hydroxy-4- aminophenyl)propionic acid to afford the product as a brown solid in 41% yield. i H NMR: CDCI 3 d: 2.60 (t, 2H), 2.82 (t, 2H), 4.58 (m, 2H), 5.27 (dd, IH), 5.31 (dd, IH), 5.90 (m, IH), 6.5-6.8 (m, 3H). b) Propen-3-yl 3 2-(2-(4-(3.5-dichlorobenzyloxy)phenoxy)-l- hvdroxyethyl)benzoxazol-5-yllpropionate. The procedure described in example 1 i was used with the product from 28a and the product from example 27d to give the required product as a light brown solid in 78% yield. l K NMR: CDC1 d: 2.70 (t, 2H), 3.08 (t, 2H), 3.30 (d, IH), 4.43 (m, 2H), 4.58 (m, 2H), 4.95 (s, 2H), 5.20-5.33 (m, 3H), 5.88 (m, IH), 6.87 (m, 4H), 7.21 (dd, IH), 7.30 (s, 3H), 7.45 (d, IH), 7.56 (d, IH). c Propen-3-yl 3-r2-(2-(4-(3.5-dichlorobenzyloxy)phenoxy)-l-oxoethyl benzoxazol-5- vnpropionate. The procedure described for example lj was used with the product from example 28b to give the product as an yellow solid in 94% yield. Mass spectrum: m/e 540 / 542 / 544 (M+ 1 ) l H NMR: CDCI 3 d: 2.74 (t, 2H), 3.14 (t, 2H), 4.58 (m, 2H), 4.97 (s, 2H), 5.21- 5.26 (m, 2H), 5.50 (s, 2H), 5.88 (m, IH), 6.88-6.99 (q, 4H), 7.26 (s, 2H), 7.31 (s, IH), 7.42 (dd, IH), 7.61 (d, IH), 7.73 (s, IH). d) 2-f2-(4-(3,5-Dichlorobenzyloxy)phenoxy)-l-oxoethvnbenzoxazoIe-5-yllpropionic acid The procedure described in example 25d was used with the product from 28c to give the required product as an off-white solid in 47% yield. Mass spectrum: m/e 500 / 502 / 504 (M+l) M.p.: 134-135°C C 2 5H 19 Cl 2 NO 6 requires: C 60.0 H 3.8 N 2.8 % found: C 59.8 H 3.8 N 3.0 % EXAMPLE 29 2-f3-r4-(Phenylpentyloxy)phenvn-l-oxopropynbenzoxazole-5- carboxylic acid a) Methyl 3-(4-(5-phenylpentyloxy)phenyl propionate A solution of methyl 3-(4-hydroxyphenyl)propionate (4.6g) in dry DMF (100 ml) was treated with sodium hydride (60% oil suspension, 1.02g) and stirred at 25°C, under an atmosphere of nitrogen for 10 mins. A solution of phenylpentyl mesylate (6.18g) in DMF (20 ml) was added dropwise and stirring was continued for 18 hrs. The reaction mixture was poured into 2N hydrochloric acid and extracted with ethyl acetate. The extract was washed with water, brine, dried (MgSO 4 ), evaporated and the resulting oil passed down a silica gel column eluted with hexane:ethyl acetate (20: 1 , v/v) to give the product as a white solid (5.85g). Mass spectrum: m/e 326 ! H NMR: CDC1 3 d: 1.45-1.85 (m, 6H), 2.61 (m, 4H), 2.88 (t, 2H), 3.66 (s,3H), 3.92 (t, 2H), 6.81-7.10 (m, 4H), 7.27-7.9 (m, 5H). b) 3-(4-(5-Phenylpentyloxy)phenyl)propionic acid The procedure described in example 9b was used with the product of 29a to give the product as a white solid in 94% yield. Mass spectrum: m/e 312 H NMR: CDC1 3 d: 1.50 (m, 2H), 1.68 (m, 2H), 1.80 (m, 2H), 2.64 (m,4H), 2.90 (t, 2H), 3.92 (t, 2H), 6.82 (d, 2H), 7.11 (d, 2H), 7.1-7.3 (m, 5H). c) N-Methyl.N-methoxy-3-f4-(5-phenylpentyloxy)phenyllpropionamide The product of 29b (5.2g) was dissolved in thionyl chloride (50 ml) and heated at reflux for 4 hrs. The mixture was evaporated and then co-evaporated with toluene (50 ml), the residue was dissolved in dry dichloromethane (100 ml) and the solution was cooled to 0°C under a nitrogen atmosphere. N,O-dimethylhydroxyamine (1.78g) was added followed by the dropwise addition of pyridine (2.96 ml). The reaction was stirred at 25°C for 3 hrs then washed with 2N hydrochloric acid, saturated sodium bicarbonate solution, brine, dried (MgSO 4 ) and evaporated to give an orange oil. The oil was passed down a silica gel column eluted with hexane:ethyl acetate (2: 1, v/v) to give the product as a colourless oil, (4.14g). Mass spectrum: m e 355 l H NMR: CDC1 3 d: 1.50 (m, 2H), 1.71 (m, 2H), 1.80 (m, 2H), 2.64 (t, 2H), 2.70 (m, 2H), 2.88 (m, 2H), 3.17 (s, 3H), 3.60 (s, 3H), 3.94 (t, 2H), 6.81 (d, 2H), 7.15 (d, 2H), 7.15-7.3 (m, 5H). d) 3-r4-(5-Phenylpentyloxy)phenvnpropionaldehvde The amide product of 29c (4. Ig) was dissolved in dry THF (30 ml), cooled to 0°C and stirred under a nitrogen atmosphere. A IM solution of lithium aluminium hydride in THF (7 ml) was added dropwise and stirring continued for 0.5 hr. A solution of sodium hydrogenphosphate (4g) in water (80 ml) was added and the mixture was extracted with ether. The extract was washed with water, brine, dried (MgSO 4 ) and evaporated to give the product as a yellow oil (3.4g). Mass spectrum: m/e 296 H NMR: CDCI 3 d: 1.51 (m, 2H), 1.71 (m, 2H), 1.82 (m, 2H), 2.65 (m, 2H), 2.76 (t, 2H), 2.91 (t, 2H), 3.92 (t, 2H), 6.82 (d, 2H), 7.10 (d, 2H), 7.15-7.85 (m, 5H), 9.81 (s, IH). e) 4-r4-(5-Phenylpentyloxy)phenyll-2-hydroxy-butyronitrile The procedure described in example lg was used with the product from 29d to give the product as a white solid in 68% yield. Mass spectrum: m/e 324 H NMR: CDCI 3 d: 1.51 (m, 2H), 1.67 (m, 2H), 1.80 (m, 2H), 2.12 (m, 2H), 2.59 (d,lH), 2.62 (t, 2H), 2.79 (t, 2H), 3.93 (t, 2H), 4.41 (m, IH), 6.82 (d, 2H), 7.10 (d, 2H), 7.15-7.30 (m, 5H). f) 4-r4-(5-Phenylpentyloxy)phenyn-2-hvdroxy-l -ethoxy-1 -iminobutane hvdrochloride The procedure described in example lh was used with the product from 29e to give the product as a white solid in 80% yield. Mass spectrum: m/e 370 (M+l) H NMR: DMSO-D 6 d: 1.32 (t, 3H), 1.43 (m, 2H), 1.63 (m, 2H), 1.72 (m, 2H), 1.90 (m, 2H), 2.60 (m, 4H), 3.91 (t, 2H), 4.36 (m, IH), 4.39 (m, 2H), 6.78 (s, IH), 6.83 (d, 2H),7.10 (d, 2H), 7.15-7.32 (m, 5H), 1 1.17 (bs, 2H). g) 2-r3-(4-(5-Phenylpentyloxy)phenyl)-l -hvdroxypropyll benzoxazole-5-carboxylic acid The procedure described in example li was used with the product from 29f to give the product as a white solid in 51 % yield. Mass spectrum: m/e 460 (M+l) M.p.: 136-137°C C 28 H 29 NO 5 requires: C 73.2 H 6.4 N 3.1 % found: C 73.1 H 6.5 N 3.1 % h) 2-r3-(4-(5-Phenylpentyloxy)phenyl)-l-oxopropynbenzoxazole-5- carboxylic acid The procedure described in example lj was used with the product from 29g to give the product as a white solid in 74% yield which analysed as the hemihydrate. Mass spectrum: m/e 458 (M+l) M.p.: 141-142°C C 28 H 27 NO 5 0.5H 2 O requires: C 72.1 H 6.1 N 3.0 % found: C 72.6 H 6.0 N 3.4 % EXAMPLE 30 2-r3-(4-(5-Phenylpentyloxy)phenyl)-l -oxopropyllbenzoxazole-6- carboxylic acid a) 2-f3-(4-(5-Phenylpentyloxy)phenyl -l -hvdroxypropyll benzoxazole-6-carboxylic acid The procedure described in example li was used with the product from 29f and 3-hydroxy- 4-aminobenzoic acid to give the product as a white solid in 45% yield. Mass spectrum: m/e 460 (M+l) M.p.: 123-124°C C 28 H 29 NO 5 requires: C 73.2 H 6.4 N 3.1 % found: C 73.0 H 6.5 N 3.2 % b) 2-r3-(4-(5-Phenylpentyloxy)phenyl)-l-oxopropyl]benzoxazole-5- carboxylic acid The procedure described in example lj was used with the product from 30a to give the product as a white solid in 53% yield. Mass spectrum: m/e 457 M.p.: 152-153°C C 28 H 27 NO 5 requires: C 73.5 H 6.0 N 3.1 % found: C 72.5 H 6.1 N 3.3 % EXAMPLE 31 3-[2-(2-(4-(5-Phenylpentylthio)phenoxy)-l-oxoethyl)-4- ethylthiazol-5-vnpropionic acid 5-Oxo-hexanoic acid was subjected to the sequence of reactions described in example 10 to give the title compound as a white solid as the monohydrate. Mass spectrum: m/e 484 (M+l) M.p.: 99-101°C C 26 H 29 NO 4 S 2 requires: C 62.3 H 6.2 N 2.8 S 12.8 % found: C 61.5 H 5.7 N 3.0 S 12.6 % EXAMPLE 32 4-f2-(2-(4-(Decylthio)phenoxy)-l-oxoethyl)-4-methylthiazol-5-yl1butanoic acid a) Ethyl 2-r4-(decylthio)phenoxy)1 acetate The procedure described for example 2a was used with 4-(decylthio)phenol and ethyl 2- bromoacetate to give the required compound as a yellow solid in 95% yield. Mass spectrum: m/e 353 (M+l) ! H NMR: CDC1 3 d: 0.88 (t, 3H), 1.2-1.35 (m, 15H), 1.4 (m, 2H), 1.6 (m, 2H), 2.82 (t, 2H), 4.29 (q, 2H), 4.6 (s, 2H), 6.86 (d, 2H), 7.33 (d, 2H). b) 4-r2-(2-(4-(Decylthio)phenoxy)-l-oxoethyl)-4-methylthiazol-5-yllbutanoicacid The procedure described in example lOe was used with the product of 32a and the product from lOd to afford the product as a yellow solid in 25% yield. Mass spectrum: m/e 492 (M+l) H NMR: CDCI 3 d: 0.88 (t, 3H), 1.2- 1.3 (m, 12H), 1.4 (m, 2H), 1.61 (m, 2H), 2.0 (m, 2H), 2.44 (s, 3H), 2.46 (t, 2H), 2.8 (t, 2H), 2.9 (t, 2H), 5.45 (s, 2H) 6.92 (d, 2H), 7.32 (d, 2H). EXAMPLE 33 4-f2-(2-(4-(Decylsulfonyl)phenoxy)-l-oxoethyl -4-methylthiazol-5-yllbutanoic acid The procedure described in example 13b was used with the product from example 32b to afford the required product as a yellow solid in 33% yield. This was converted to the dicyclohexylamine salt and analysed as the monohydrate. Mass spectrum: m e 524 (M+l) M.p.: 139°C C 38 H 6 oN 2 O6S 2 • H 2 O requires: C 63.1 H 8.6 N 3.9 S 8.9 % found: C 63.5 H 8.4 N 4.0 S 8.8 % EXAMPLE 34 2-r2-(2-(4-(3.5-Dichlorobenzyloxy)phenoxy)-l-oxoethyl)benzothiazol-6-oxy1acetic acid a) (l.l-Dimethyl)ethyl 2-(benzothiazol-6-oxy)acetate Using the procedure described in example 5a with 6-hydroxybenzothiazole and (1,1- dimethyl)ethyl 2-bromoacetate gave the required product as a yellow oil in 97% yield. Mass spectrum: m/e 266 (M+l) Η NMR, CDC1 3 , d: 1.49 (s, 9H), 4.60 (s, 2H), 7.17 (dd, IH)), 7.39 (d, IH), 8.04 (d, IH), 8.86 (s, IH). b) 2-(Benzothiazol-6-oxy)acetic acid The procedure described in example 5b was used with the product from 34a to give the required product as an off-white solid in quantitative yield. Mass spectrum: m/e 210 (M+l) Η NMR, CDC1 3 , d: 4.77 (s, 2H), 7.16 (dd, IH)), 7.70 (d, IH), 7.98 (d, IH), 8.35 (s, IH), 9.20(s, IH). c) 2-r2-(2-(4-(3,5-Dichlorobenzyloxy)phenoxy)-l-oxoethyl)benzothiazol-6-oxy1acetic acid The procedure described in example 8 was used with the product from 34b and the product from 1 lb to give the required product as a yellow solid in 22% yield. Mass spectrum: m/e 518 / 520 / 522 (M+l ) M.p.: 179-180°C C 24 Hι 7 Cl 2 NO 6 S requires: C 55.6 H 3.3 N 2.7 S 6.2 % found: C 55.6 H 3.3 N 2.5 S 5.9 % EXAMPLE 35 4-r2-(2-(4-(5-Phenylpentyloxy)phenoxy)-l-oxoethyl)-4-methylthiazol-5-yllbutanoic acid a) 5-Phenylpentyl tosylate 5-Phenylpentanol (12.7g) was dissolved in chloroform (200 ml) and the solution cooled to 0°C. Pyridine (6.9 ml) was added followed by portionwise addition of tosyl chloride (16.2g). The reaction mixture was stirred at ambient temperature for 16 hrs then washed with water, dried (MgSO ) and evaporated to leave a colourless oil. The oil was passed down a silica gel column eluted with hexane:ethyl acetate (4: 1) to afford the product as a colourless oil (17.7g). Η NMR, CDC1 3 , d: 1.32-1.4 (m, 2H), 1.5-1.59 (m, 2H), 1.6-1.69 (m, 2H) 2.44 (s, 3H), 2.56 (t, 2H), 4.01 (t, 2H), 7.1-7.2 (m, 3H) 7.24-7.29 (m, 2H), 7.35 (d, 2H), 7.75 (d, 2H). b) 4-(5-Phenylpentyloxy)phenol Quinol (8.3g) was dissolved in acetonitrile (200 ml) and treated with caesium carbonate (24.5g) and the tosylate from 35a (8.0g). The mixture was heated at 85oC for 24 hrs. The mixture was cooled to ambient temperature, poured into 2N hydrochloric acid (200 ml) and extracted into ethyl acetate. The extract was washed with water, brine, dried (MgSO4) and evaporated to give a solid. The solid was passed down a silica gel column eluted with hexane:ethyl acetate (4: 1) to afford the product as a white solid (3.0g). Mass spectrum: m/e 256 Η NMR, CDC1 3 , d: 1.47-1.53 (m, 2H), 1.65-1.7 (m, 2H), 1.75-1.8 (m, 2H) 2.64 (t, 2H), 3.9 (t, 2H), 4.4 (s, IH), 6.74-6.8 (dd, 4H) 7.16-7.2 (m, 3H), 7.26-7.3 (m, 2H). c) Ethyl 2-f4-(5-phenvIpentyloxy)phenoxylacetate. The procedure described in example 2a was used with the product from 35b to give the required product as a yellow solid in 90% yield. Mass spectrum: m/e 342 Η NMR, CDC1 3 , d: 1.29 (t, 3H), 1.47-1.52 (m, 2H), 1.65-1.71 (m, 2H), 1.74- 1.79 (m, 2H) 2.64 (t, 2H), 3.89 (t, 2H), 4.26 (q, 2H), 4.56 (s, 2H) 6.8-6.86 (dd, 4H), 7.18 (m, 3H), 7.26-7.29 (m, 2H). d) 4-r2-(2-(4-(5-Phenylpentyloxy)phenoxy)-l-oxoethyl)-4-methylthiazol-5-vnbutanoic acid The procedure described in example 8 was used with the product from 35c and the product from lOd to give the required product as a yellow solid in 20% yield. Mass spectrum: m/e 482 (M+l) M.p.: °C 127-128 C 27 H 31 NO 5 S requires: C 67.3 H 6.5 N 2.9 S 6.7 % found: C 66.8 H 6.4 N 2.9 S 6.4 % EXAMPLE 36 5-r2-(2-(4-(5-Phenylpentyloxy phenoxy)-l-oxoethyl)thiazol-4-yllpentanoic acid a) Methyl 7-bromo-6-oxo-heptanoate To a solution of 6-oxoheptanoic acid (6.06g) in methanol (100 ml) was added dropwise a solution of bromine (7.2g) in «*ethanol {20 ml). The mixture was then stirred at 25°C for 18 hrs. The solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate (250 ml). This was washed with a saturated solution of sodium bicarbonate, water, brine, dried (MgSO 4 ) and evaporated to a gum which was passed down a silica gel column eluted with hexane:ether (3:1, v/v). The appropriate fractions were combined and evaporated to give the product as a pale yellow oil, (3.05g). Mass spectrum: m/e 236 / 238 (M+) Η NMR, CDC1 3 , d: 1.6- 1.7 (m, 4H), 2.3-2.4 (m, 2H)), 2.66-2.72 (m, 2H), 3.67 (s, 3H), 3.88 (s, 2H). b) Methyl 5-(thiazol-4-yl)pentanoate Formamide (10 ml) in toluene (30 ml) was treated with phosphorus pentasulphide (3.5g). Methyl 7-bromo-6-oxoheptanoate (2.6g) was added and the mixture was heated at 75 °C for 2 hrs. The reaction mixture was allowed to cool to ambient temperature, neutralised with 10% sodium hydroxide solution and extracted with ethyl acetate. The extract was washed with water, brine, dried (MgSO 4 ) and evaporated to give a gum. This was passed down a silica gel column eluted with hexane:ethyl acetate (3:2, v/v) to afford the product as a colourless oil (1.37g). Mass spectrum: m/e 200 (M+l) Η NMR, CDC1 3 , d: 1.6- 1.8 (m, 4H), 2.36 (t, 2H)), 2.86 (t, 2H), 3.67 (s, 3H), 6.96 (d, IH), 8.74(d, IH). c) 5-(Thiazol-4-yl)pentanoic acid The procedure described in example lOd was used with the product from 36a to give the required product as a yellow solid in 94% yield. Mass spectrum: m/e 186 (M+l) 1H NMR, CDC1 3 , d: 1.7- 1.9 (m, 4H), 2.40 (t, 2H)), 2.87 (t, 2H), 6.97 (d, IH), 8.79(d, IH). d) 5-r2-(2-(4-(5-Phenylpentyloxy)phenoxy)-l -oxoethyl)thiazol-4-yllpentanoic acid The procedure described in example 8 was used with the product from 36b and the product from 35b to give the required product as a yellow solid in 24% yield. Mass spectrum: m/e 482 (M+l) M.p.: 78-80°C C 27 H 31 NO 5 S requires: C 67.3 H 6.5 N 2.9 S 6.7 % found: C 67.8 H 6.5 N 2.9 S 6.1 % EXAMPLE 37 4-r2-(2-(4-(5-Phenylpentyloxy)phenyl)-l-oxopropyl) -4-methylthiazol-5-yllbutanoic acid a) Methyl 4-(4-methylthiazol-5-yl)butanoate Using the procedure described in 36b, with methyl 5-bromo-6-oxo-heptanoate led to the required product as a yellow solid in 74% yield. ! H NMR, CDC1 3 , d: 1.95 (m, 2H), 2.36 (t, 2H), 2.38 (s, 3H), 2.82 (t, 2H), 3.68 (s, 3H), 8.56 (s, IH). b) 4-(4-methylthiazol-5-yl)butanoic acid Using the procedure described in 9b, with the product from 37a, led to the required product as a white solid in 63% yield. Mass spectrum : m/e 186 (M+l) l K NMR, DMSO d6 , d: 1.76 (m, 2H), 2.26 (t, 2H), 2.29 (s, 3H), 2.77 (t, 2H), 8.81 (s, IH), 12.11 (s, IH). c) 4-r2-(2-(4-(5-Phenylpentyloxy)phenyl)-l-oxopropyl) -4-methylthiazol-5-yllbutanoic acid The procedure described in example 8 was used with the product from 37b and the product from 29a to give the required product as a yellow solid in 10% yield. Mass spectrum: m e 480 M.p.: 121-122°C EXAMPLE 38 4-r2-(2-(4-(Benzylthio)phenoxy)-l-oxoethyl)-4-methylthiazol-5-yllbutanoic acid The procedure described in example 8 was used with the product from 37b and the product from 15b to give the required product as a white solid in 25% yield. Mass spectrum: m/e 442 (M+H) M.p.: °C 131-132 C 23 H 23 NO 4 S 2 requires: C 62.6 H 5.3 N 3.2 S 14.5 % found: C 61.8 H 5.1 N 3.3 S 14.0 % EXAMPLE 39 2-r2-(4-(3,5-Dichlorobenzyloxy)phenoxy)-l -oxoethvπbenzothiazole-6- carboxylic acid The procedure described in example 8 was used with the product from 1 lb to give the required product as a white solid in 20% yield. Mass spectrum: m/e 486 / 488 / 490 (M+H) M.p.: °C 205-205 C 23 H 15 Cl 2 NO 5 S requires: C 56.6 H 3.1 N 2.9 S 6.6 % found: C 55.4 H 3.1 N 3.0 S 6.6 % EXAMPLE 40 4-r2-(2-(4-(5-Phenylpentylthio)phenoxy)-l-oxopropyl)-4-methylthiazol-5-vnbutanoic acid a) Ethyl 2-r4-(5-phenylpentylthio)phenoxylpropionate The procedure described in example 2a was used starting with ethyl 2-bromopropionate to give the product as a colourless oil in 87% yield. Mass spectrum: m/e 373 (M+H) 1H NMR, CDC1 3 , d: 1.24 (t, 3H), 1.41 (m, 2H), 1.51-1.65 (m & d, 7H), 2.59 (t, 2H), 2.80 (t, 2H), 4.21 (q, 2H), 4.70 (q, 1 H), 6.80 (d, 2H), 7.14-7.21 (m, 3H), 7.24-7.31(m, 4H). b) 4-r2-(2-(4-(5-Phenylpentylthio)phenoxy)-l-oxopropyl)-4-methylthiazol-5- yllbutanoic acid The procedure described in example lOe was used with the product from 40a to give the required product as a pale yellow gum in 43% yield. The product was converted to the dicyclohexylamine salt which was a pale yellow solid. Mass spectrum: m/e 512 (M+H) M.p.: °C 107-108 C 40 H 56 N 2 O 4 S 2 requires: C 69.3 H 8.2 N 4.0 S 9.3 % found: C 69.6 H 8.2 N 4.3 S 9.3 % EXAMPLE 41 4- 2-(2-(4-(5-Phenylpentylthio)phenoxy)-l-oxo-2-methyl-propyl)-4-methylthiazol-5- yllbutanoic acid a) Ethyl 2-f4-(5-phenylpentylthio)phenoxyl2-methylpropionate The procedure described in example 40a was used starting with ethyl 2-bromo-2- methylpropionate to give the product as a colourless oil in 45% yield. b) 4-r2-(2-(4-(5-Phenylpentylthio)phenoxy)-l-oxo-2-methylpropyl)-4-methylthiazol-5- yllbutanoic acid The procedure described in example lOe was used with the product from 41a to give the required product as a pale yellow gum in 22% yield. Mass spectrum: m/e 526 (M+H) Η NMR, CDC1 3 , d: 1.42 (m, 2H), 1.61 (m, 4H), 1.76 (s, 6H), 1.95 (m, 2H), 2.44 (s & m, 5H), 2.60 (t, 2H), 2.83 (m, 4H), 6.77 (d, 2H), 7.13- 7.29 (m, 7H). EXAMPLE 42 4- 2-(2-(4-(5-Phenylpentylthio)phenoxy)-2-phenyl-l-oxyethyl)-4-methylthiazol-5- yllbutanoic acid a) Methyl 2-r4-(5-phenylpentylthio)phenoxyl2-phenylacetate The procedure described in example 40a was used starting with methyl 2-bromo-2- phenylacetate to give the product as a white solid in 75% yield. Mass spectrum: m/e 421 (M+H) 1H NMR, CDC1 3 , d: 1.44 (m, 2H), 1.61 (m, 4H), 2.58 (t, 2H), 2.81 (t, 2H), 3.74 (s,3H), 5.60 (s, IH), 6.85(d, 2H), 7.15 (m, 3H), 7.25 (m, 4H), 7.41 (m,3H), 7.55 (m,2H). b) 4-r2-(2-(4-(5-Phenylpentylthio)phenoxy)-l-oxo-2-phenylethyl)-4-methylthiazol-5- yllbutanoic acid The procedure described in example lOe was used with the product from 42a to give the required product as a pale yellow gum in 8% yield. This was converted to the dicyclohexyllamine salt to afford a white solid, which analysed as the hydrate. Mass spectrum: m/e 574 (M+H) M.p.: °C 121-122 C 45 H 58 N 2 O 4 S 2 .H 2 0 requires: C 69.9 H 7.8 N 3.6 S 8.3 % found: C 70.0 H 7.4 N 3.5 S 7.8 % EXAMPLE 43 4. 2-(2-(4-(5-Phenylpentylthio)phenoxy -3-methyl-l-oxobutyl)-4-methylthiazol-5- yllbutanoic acid a) Ethyl 2-r4-(5-phenylpentylthio)phenoxyl3-nιethylbutanoate The procedure described in example 40a was used starting with ethyl 2-bromo-3- methylbutanoate to give the product as a clear oil in 35% yield. Mass spectrum: m/e 401 (M+H) Η NMR, CDC1 3 , d: 1.05-1.09 (2xt, 6H), 1.24 (t,3H), 1.43 (m, 2H), 1.60 (m, 4H), 2.27 (m, IH), 2.59 (t,2H), 2.80 (t, 2H), 4.21 (q, 2H), 4.32 (d, IH), 6.82 (d, 2H), 7.17 (m, 3H), 7.24-7.30 (m, 4H). b) 4-r2-(2-(4-(5-Phenylpentylthio)phenoxy)-3-methyl-l-oxobutyl)-4-methylthiazol-5- yllbutanoic acid The procedure described in example lOe was used with the product from 42a to give the required product as a pale yellow gum in 1 1 % yield. This was converted to the dicyclohexyllamine salt to afford a white solid. Mass spectrum: m/e 540 (M+H) M.p.: °C 111-1 12 C 42 H 60 N 2 O 4 S 2 requires: C 69.9 H 8.4 N 3.9 S 8.9 % found: C 69.8 H 8.5 N 3.9 S 9.2 % EXAMPLE 44 2-r2-(4-(5-PhenvIpentylthio)phenoxy)-l-oxoethvnbenzimidazole-5-carboxylic acid a) 2-r2-(4-(5-Phenylpentylthio)phenoxy)-l-hydroxyethvnbenzimidazole-5-carboxylic acid The procedure described in example li was used with 3,4-diaminobenzoic acid to afford the required product as a light brown solid in 70% yield. Mass spectrum: m/e 478 (M+H) Η NMR, CDCI 3 , d: 1.36 (m, 2H), 1.53 (m, 4H), 2.53 (t, 2H), 2.82 (t, 2H), 4.26-4.45 (m, 2H) 5.20 (m, IH), 6.37 (d,lH) 6.94 (d, 2H), 7.12-7.29 (m, 7H), 7.58 (dd, IH), 7.80 (m, IH), 8.12 (d, IH). b) 2-r2-(4-(5-Phenylpentylthio)phenoxy)-l -oxoethyllbenzimidazole-5-carboxylic acid The procedure described in example li was used with the product from 44a to afford the required product as a cream coloured solid in 32% yield, as the hemi-hydrate. Maββ-βpectrum: m/e 475 (M+H) M.p.: °C 186-188 C 27 H 26 N 2 O 4 S.0.5H 2 O requires: C 67.1 H 5.6 N 5.8 S 6.6 % found: C 67.7 H 5.6 N 5.9 S 6.7 % EXAMPLE 45 2-r2-r4-(5-Phenylpentylthio)phenoxyl-l-oxoethvπimidazole a) l-Triphenylmethyl-2-r2-r4-(5-Phenylpentylthio)phenoxyl-l-oxoethvnimidazole The procedure described in example 2b was used with 1-triphenylmethylimidazole to afford the required product as a colourless oil in 37% yield. 1H NMR, CDC1 3 , d: 1.44 (m, 2H), 1.60 (m, 4H), 2.59 (t, 2H), 2.76 (t, 2H), 5.18 (s, 2H), 6.33 (d,2H) 7.06 (m, 6H), 7.12-7.19 (m, 7H), 7.25-7.28 (m, 11H). b) 2-r2-r4-(5-Phenylpentylthio)phenoxyl-l-oxoethvni idazole The product from example 45a (0.64g) was dissolved in dichloromethane (50 mis) and treated with trifluoroacetic acid (8 mis) and stirred at 25°C for 0.5 hr. The reaction mixture was then poured into a 5% solution of sodium hydroxide in water (200 mis) and extracted with dichloromethane. The extract was dried (MgSO4) and evaporated to dryness. The residue was passed down a silica gel columned eluted with hexane:ethyl acetate (2:1) to afford the required product as a white solid (0.32g). Mass spectrum: m/e 381 (M+H) M.p.: °C 162-163 C 22 H 24 N 2 O 4 S requires: C 69.4 H 6.4 N 7.4 S 8.4 % found: C 69.6 H 6.5 N 7.0 S 8.2 % EXAMPLE 46 3-f2-f2-r4-(5-Phenylpentylthio)phenoxyl-l-oxoethyll-4- ethylimidazol-5-yllpropenoic acid a) (l-Triphenylmethyl-4-methylimidazol-5-yl)carboxaldehyde 4-Methyl-imidazole-5-carboxaldehyde (2.0 g) was dissolved in DMF (40 mis) and treated with triethylamine (1.84 g). Triphenylmethylchloride (5.06g) in DMF (40 mis) was added over 0.5 hr and the reaction was stirred at ambient temperature for 18 hrs. The reaction mixture was poured into water and extracted into ethyl acetate. The extract was washed with water, brine, dried (MgSO4) and evaporated to afford an oil. This was passed down a silica gel column eluted with hexane:ethyl acetate (1:1) to give the product as a white solid (2.39 g). H NMR, CDC1 3 , d: 1.6 (s, IH), 7.10-7.19 (m, 6H), 7.34-7.38 (m, 9H),7.39(s,lH), 10.00 (s, IH). b) Ethyl 3-(l-Triphenylmethyl-4-methylimidazol-5-yl)propenoate The product from example 46a (2.39 g) was dissolved in dichloromethane (50 mis) and treated with (carbethoxymethylene)phosphorane (2.36 g) and stirred at ambient temperature for 24 hrs. The reaction was then stirred at reflux for 72 hrs. The solvent was removed under reduced pressure and the residue purified by silica gel chromatography, eluted with hexane:ethyl acetate (3:2), to give the required product as a white solid (1.45g). H NMR, CDC1 3 , d: 1.29 (t, 3H), 1.57 (s, 3H), 4.22 (q, 2H), 6.58 (d, IH), 7.12-7.17 (m, 6H), 7.26-7.36 (m, 10H), 7.55 (d,lH). c) 3-(l-Triphenylmethyl-4-methylimidazol-5-yl)propenoic acid The product from example 46b (1.45 g) was dissolved in tetrahydrofuran (40 mis) and water (10 mis) was added. Lithium hydroxide monohydrate (0.43 g) was added followed by a few drops of methanol and the mixture stirred at room temperature for 18 hrs. The mixture was then heated at reflux for 6 hrs, then poured into a saturated solution of ammonium chloride (30 mis) and extracted into ethyl acetate. The extracts were washed with water, brine, dried (MgSO4) and evaporated to dryness to give the product as a white solid (1.27 g). H NMR, CDCI 3 , d: 1.57 (s, 3H), 6.60 (d, IH), 7.11-7.19 (m, 6H), 7.32-7.36 (m, 9H), 7.41 (s, IH), 7.62 (d, IH). cQ 3-r2-r2-r4-f5-Phenylpentylthio)phenoxyl-l-oxoethyll-l-triphenylmethyl-4- methylimidazol-5-yllpropenoic acid The procedure described in example 8 was used with the product from example 46c to give the required product in 21% yield. Η NMR, CDC1 3 , d: 1.44 (m, 2H), 1.59 (m, 4H), 1.74 (s, 3H), 2.59 (m, 2H) 2.79 (t, 2H), 5.1 1 (s, 2H), 6.85 (d,lH), 6.75 (d,2H) 7.1-7.19 (m, 9H), 7.24-7.39 (m, 13H), 7.62 (d,lH). e) 3-r2-r2-r4-(5-Phenylpentylthio)phenoxyl-l-oxoethyll-4-methyliιnidazol-5- yllpropenoic acid The procedure described in example 45b was used with the product from example 46d to afford the required product in 10% yield. Mass spectrum: m/e 465 (M+H) Η NMR, CDC1 3 , d: 1.44 (m, 2H), 1.61 (m, 4H), 2.40 (s, 3H), 2.60 (t, 2H) 2.81 (t, 2H), 5.45 (s, 2H), 6.60 (d,lH), 6.93 (d,2H) 7.14 (m, 3H), 7.16-7.32 (m, 4H), 7.61 (d,lH) > 13.1 (bs, IH). EXAMPLE 47 2- r 2-(4-(5-Phenylpentylthio)phenoxy)-l-oxoethyHpyridine Using the procedure described for example 5d but using 2-bromopyridine in place of 1- methylimidazole led to the preparation of the required compound as a white solid in 57% yield. Mass spectrum: m/e 392 (M+H) M.p.: 68°C C 24 H 25 NO 2 S requires: C 73.6 H 6.4 N 3.6 S 8.2 % found: C 74.6 H 6.5 N 3.7 S 8.1 % EXAMPLE 48 4-r2-(2-(4-(5-Phenylpentyloxy)phenoxy)-l-oxopropyl)-4-methylthiazol-5-vnbutanoic acid a) Ethyl 2-r4-(5-phenylpentyloxy)phenoxylpropionate The procedure described in example 2a was used starting with ethyl 2-bromopropionate and (5-phenylpentyloxy)phenol to give the product as a colourless gum. Mass spectrum: m/e 366 (M+H) Η NMR, CDC1 3 , d: 1.27 (t, 3H), 1.49 (m, 2H), 1.56-1.83 (m & d, 7H), 2.64 (t, 2H), 3.89 (t, 2H), 4.16 (q, 2H), 4.64 (q, IH), 6.77-6.84 (m, 4H), 7.15-7.30 (m, 5H). b) 4-f2-(2-(4-(5-Phenylpentvoxy)phenoxyH-oxopropyl)-4-methylthiazol-5- yllbutanoic acid The procedure described in example lOe was used with the product from 48a to give the required product as a pale yellow gum. The product was converted to the dicyclohexylamine salt which was a pale yellow solid. Mass spectrum: m/e 496 (M+H) M.p.: °C 91-93 C 40 H 56 N 2 O 5 S requires: C 70.9 H 8.3 N 4.1 S 4.7 % found: C 70.7 H 8.2 N 4.1 S 4.9 % EXAMPLE 49 4-f2-(2-(4-(4-Chlorobenzylthio)phenoxy)-l-oxopropyl)-4-methylthiazol-5-ynbutanoic acid a) 4-(4-Chlorobenzylthio phenol The procedure described in example 13a was used with 4-hydroxythiophenol and 4- chlorobenzyl chloride to give the required product as a pale yellow solid in 59% yield. 1H NMR, CDC1 3 , d: 3.91 (s, 2H), 4.94 (s, IH), 6.70 (d, 2H), 7.1 (d, 2H) 7.21 (dd, 4H). b Ethyl 2-r4-(4-chlorobenzylthio)phenoxylpropionate The procedure described in example 2a was used with ethyl 2-bromopropionate and 4-(4- chlorobenzylthio)phenol to give the required product as a white solid in 93% yield. Η NMR, CDC1 3 , d: 1.26 (t, 3H), 1.60 (d, 3H), 3.92 (s, 2H), 4.20 (q, 2H), 4.71 (q, IH), 6.77 (d, 2H), 7.1 (d, 2H), 7.22 (m, 4H). c) 4-r2-(2-(4-(4-Chlorobenzylthio)phenoxy)-l-oxopropyl)-4-methylthiazol-5- yllbutanoic acid The procedure described in example lOe was used with the product from 49b to give the required product as a pale yellow gum. The product was converted to the dicyclohexylamine salt which was a pale yellow solid. Mass spectrum: m e 490 / 492 (M+H) M.p.: °C 106-107 C 36 H 47 CIN 2 O 4 S 2 requires: C 64.4 H 7.1 N 4.2 S 9.6 % found: C 63.7 H 7.1 N 4.1 S 9.3 % EXAMPLE 50 4-r2-(2-(4-(4-Chlorobenzylthio)phenoxy)-l-oxobutyl)-4-methylthiazol-5-yllbutanoic acid a) Ethyl 2-r4-(4-chlorobenzylthio)phenoxylbutanoate The procedure described in example 2a was used with ethyl 2-bromobutanoate and 4-(4- chlorobenzylthio)phenol to give the required product as a white solid in 94% yield. 1H NMR, CDC1 3 , d: 1.07 (t, 3H), 1.25 (t, 3H), 1.98 (m, 2H), 3.92 (s, 2H), 4.20 (q, 2H), 4.50 (t, IH), 6.77 (d, 2H), 7.1 (d, 2H), 7.21 (m, 4H). b) 4-r2-(2-(4-(4-Chlorobenzylthio)phenoxy)-l-oxobutyl)-4-methylthiazol-5- yllbutanoic acid The procedure described in example lOe was used with the product from 50a to give the required product as a pale yellow gum. The product was converted to the dicyclohexylamine salt which was a pale yellow solid. Mass spectrum: m/e 504 / 506 (M+H) M.p.: °C 114-116 C 37 H 49 CIN 2 O 4 S 2 requires: C 64.8 H7.2 N4.1 S 9.4 %, found: C 64.9 H7.5 N4.2 S 9.2 % Pharmacological Data In vivo, PLA 2 is responsible for the release of arachidonic acid and lysophospholipid from cell membrane phospholipids. Arachidonic acid and certain lysophospholipids are metabolised to substances which are important mediators of the inflammatory response. The usefulness of the compounds according to the invention as anti-inflammatory agents was therefore tested in vitro by measuring their ability to inhibit arachidonic acid release from PLA 2 enzyme provided with a suitable substrate. Cell Assay Compounds according to the invention were assayed for inhibition of release of [ 3 H] arachidonic acid from DMSO-differentiated HL60 cells in response to Ca 2+ ionophore challenge. Cells of the human leukaemic line HL60 are differentiated to a Polymoφhonuclear cell-like phenotype by treatment with 1.3% DMSO for 4 days. During the final 24 hours of differentiation, the cells are incubated with [ 3 H] arachidonic acid. After washing to remove unincoφorated [ 3 H]arachidonic acid, the cells (at 2.6x10 6 /ml) are incubated for 10 minutes at 37°C with the compound of interest at concentrations up to lOμM. Arachidonic acid release is then stimulated by the addition of the Ca 2+ ionophore A23187. Control cells are incubated with vehicle alone. After 3 minutes, ice-cold MeOH is added to terminated the reaction and precipitate cellular protein and membranes. The assay reactions are then filtered to separate cellular material from the supernatant, containing the released [ 3 H] arachidonic acid. The amount of released H in the supernatant is then measured, and the inhibition of the stimulated release by the compounds is calculated. In this screen, the compounds of the examples 1, 3, 8-10, 12, 13, 15, 16, 18, 20, 21, 24-28, 31-40, 42-44, 46 and 47-50 were tested and gave ID 50 values less than 10 μM, indicating that they had useful activity.

Claims: CLAIMS: 1. A compound of formula I wherein :- R represents hydrogen, Cl to 12 alkyl, phenyl or a 5 or 6 membered heterocyclic ring containing from 1 to 3 atoms selected from O, N or S, which alkyl, phenyl or heterocyclic ring is optionally substituted by halogen, or which alkyl is optionally substituted by a group J, where J is phenyl or phenyl fused with one or two benzene rings, or biphenylyl, optionally ring substituted by 1 to 3 heteroatoms selected from O, N or S, each group J being optionally substituted by Cl to 6 alkyl, -hydroxy, Cl to 6 alkoxy, nitro or halogen; 2 3 for R and R :- 2 10 (i) R represents hydrogen, Cl to 6 alkyl or R -B; and 3 10 R represents hydrogen, Cl to 6 hydroxyalkyl, C3 to 9 alkenylcarboxyl or R -B, wherein R 10 represents Cl to 6 alkyl and B represents COOH, PO3H2, OPO3H2, SO3H, OSO3H, tetrazolyl, CONR 1 ^H or CONHSO2R 1 R 1 representing hydrogen or C l to 6 alkyl; or 2 3 (ii) R and R together represent a benzo ring or a six membered aromatic heterocyclic ring containing 1 to 3 nitrogen atoms, which benzo or heterocyclic 4 4 ring is optionally substituted by R , wherein R represents hydrogen, Cl to 6 alkoxy, Cl to 6 carboxyalkoxy, C3 to 9 alkenylcarboxyl, R -B or -(CH 2 ) p CO 2 PG, wherein R represents Cl to 6 alkyl and B represents COOH, PO3H2, OPO 3 H , SO3H, OSO3H, tetrazolyl, CONR 1 OH or CONHSO2R 1 \ R 1 representing hydrogen or Cl to 6 alkyl, and PG is allyl or tert-butyl and p represents zero or an integer from 1 to 6; 8 9 R and R independently represent hydrogen, methyl, Cl to 6 alkyl, aryl or heteroaryl, or 8 9 together R and R represent C3 to 6 cycloalkyl or a 3, 4, 5 or 6 membered heterocyclic ring containing from 1 to 3 atoms selected from O, N or S; Ar represents phenyl, or phenyl fused with one or two benzo rings, or biphenylyl optionally ring substituted with 1 to 3 heteroatoms selected from O, N or S, each Ar group being optionally substituted by Cl to 6 alkyl, hydroxy, Cl to 6 alkoxy, nitro or halogen; X represents O, S, SO , CH 2 or SO; 5 ς YY rreepprreesseennttss OO,, N NRR oorr ((CCHH22)) aa ,, whheer: e a represents an integer from 1 to 12 and R " represents hydrogen or Cl to 6 alkyl; Z represents O, S, CH=CH, N=N, N=CH or NR , where R represents hydrogen or Cl to 6 alkyl; and n represents an integer from 1 to 12; or a pharmaceutically acceptable salt, enantiomer or tautomer thereof. 2. A compound according to claim 1 wherein R represents phenyl, dichlorophenyl or methyl. 2 3. The compound according to claim 1 or 2 wherein R is according to option (i) and represents hydrogen, methyl or -(CH2)4CO2H. 3 4. The compound according to claim 1, 2 or 3 wherein R is according to option (i), it represents hydrogen, -(CH 2 )2OH, -CO 2 H, -(CH 2 )3CO 2 H, -(CH 2 )2CO 2 H or CH=CH- CO 2 H.. 2 3 5. The compound according to claim 1 or 2 wherein R and R are according to option (ii) and R 4 represents -CO 2 H, methoxy, -(CH 2 )2CO 2 H, -OCH 2 CO 2 H or -(CH 2 ) p CO 2 PG, where PG is allyl or tert-butyl and p represents zero or an integer from 1 to 6. 6. The compound according to any preceding claim wherein a represents an integer from l to 3. 7. The compound according to any preceding claim wherein Y represents O or CH2. 8. The compound according to any preceding claim wherein X represents O or S or SO2. 9. The compound according to any preceding claim wherein Z represents O, S, CHCH or NR , R representing hydrogen or methyl. 0 10. The compound according to any preceding claim wherein R represents hydrogen or methyl. 9 11. The compound according to any preceding claim wherein R represents hydrogen, methyl, phenyl or isopropyl. 12. A compound of formula (I) selected from: 2-[2-(4-(5-phenylpentylthio)phenoxy)- 1 -oxoethyl]benzoxazole-5-carboxylic acid; or 1 -methyl-2-[2-[4-(5-phenylpentylthio)phenoxy]- 1 -oxoethyl]benzimidazole; or 5-(2-hydroxyethyl)-4-methyl-2-[2-(4-(5-phenylpentylthio)phenoxy)-l-oxoethyl]thiazole; or 6-methoxy-2-[2-[4-(5-phenylpentylthio)phenoxy]-l-oxoethyl]benzothiazole; or 1 -methyl-2-[2-(4-(5-phenylpentylthio)phenoxy)- 1 -oxoethyl]imidazole; or 2-[2-(4-(5-phenylpentylthio)phenoxy)- 1 -oxoethyllbenzothiazole; or 2-[2-(4-(5-phenylpentylthio)phenoxy)- 1 -oxoethyl jthiazole; or 2-[2-(4-(5-phenylpentylthio)phenoxy)-l-oxoethyllbenzothiazole-6-carboxylic acid; or 4-methyl-2-[2-(4-(5-phenylpentylthio)phenoxy)- 1 -oxoethyl]thiazole-5-carboxylic acid; or 4-[2-(2-(4-(5-phenylpentylthio)phenoxy)- 1 -oxoethyl)-4-methylthiazol-5-yl]butanoic acid; or 2-[2-(4-(3 ,5-dichlorobenzyloxy)phenoxy)- 1 -oxoethyllthiazole; or 5-(2-hydroxyethyl)-4-methyl-2-[2-(4-(3,5-dichlorobenzyloxy)phenoxy)-l- oxoethyl]thiazole; or 5-(2-hydroxyethyl)-4-methyl-2-[2-(4-(decylsulfonyl)phenoxy)-l -oxoethyllthiazole; or 5-(2-hydroxyethyl)-4-methyl-2-[2-(4-(benzyloxy)phenoxy)- 1 -oxoethyllthiazole; or 5-(2-hydroxyethyl)-4-methyl-2-[2-(4-(benzylthio)phenoxy)- 1 -oxoethyllthiazole; or 5-(2-hydroxyethyl)-4-methyl-2-[2-(4-(3,5-dichlorobenzylthio)phenoxy)- 1 - oxoethyllthiazole; or 1 -methyl-2-[2-(4-(5-phenylpentylsulfonyl)phenoxy)- 1 -oxoethyllbenzimidazole; or 2-[2-(4-(5-phenylpentylsulfonyl)phenoxy)- 1 -oxoethyllbenzothiazole; or 2-[2-(4-(5-phenylpentylsulfonyl)phenoxy)- 1 -oxoethyl]-6-methoxybenzothiazole; or 5-(2-hydroxyethyl)-4-methyl-2-[2-(4-(3,5-dichlorobenzylsulfonyl)phenoxy)-l- oxoethyllthiazole; or 2-[2-(4-(3,4-dichlorobenzylthio)phenoxy)- 1 -oxoethyllbenzoxazole; or 2-[2-(4-(3,4-dichlorobenzylthio)phenoxy)- 1 -oxoethyl] benzimidazole; or 2-[2-(4-(3,4-dichlorobenzylthio)phenoxy)-l-oxoethyl]-6-methoxy benzoxazole; or 2-[2-(4-(3,4-dichlorobenzylthio)phenoxy)-l-oxoethyl]benzoxazole-5-carboxylic acid; or 2-[2-(4-(3 ,4-dichlorobenzylthio)phenoxy)- 1 -oxoethyl]benzoxazole-6-carboxylic acid; or 2-[2-(4-(3,5-dichlorobenzyloxy)phenoxy)-l-oxoethyllbenzoxazole-5-carboxylic acid; or 2-[2-(4-(3,5-dichlorobenzyloxy)phenoxy)-l-oxoethyllbenzimidazole-5-carboxylic acid; or 3-[2-(2-(4-(3,5-dichlorobenzyloxy)phenoxy)-l-oxoethyl)benzoxazol-5-yl]propionic acid; or 5 2-[3-[4-(phenylpentyloxy)phenyll-l-oxopropyl]benzoxazole-5- carboxylic acid; or 2-[3-(4-(5-phenylpentyloxy)phenyl)-l-oxopropyl]benzoxazole-6- carboxylic acid; or 3-[2-(2-(4-(5-phenylpentylthio)phenoxy)- 1 -oxoethyl)-4-methylthiazol-5-yl]propionic acid; or 4-[2-(2-(4-(decylthio)phenoxy)- 1 -oxoethyl)-4-methylthiazol-5-yllbutanoic acid; or o 4-[2-(2-(4-(decylsulfonyl)phenoxy)- 1 -oxoethyl)-4-methylthiazol-5-yl]butanoic acid; or 2-[2-(2-(4-(3,5-dichlorobenzyloxy)phenoxy)-l-oxoethyl)benzothiazol-6-oxy]acetic acid; or 4-[2-(2-(4-(5-phenylpentyloxy)phenoxy)- 1 -oxoethyl)-4-methylthiazol-5-yllbutanoic acid; or 5-[2-(2-(4-(5-phenylpentyloxy)phenoxy)- 1 -oxoethyl)thiazol-4-yl]pentanoic acid; or s 4-[2-(2-(4-(5-phenylpentyloxy)phenyl)- 1 -oxopropyl)-4-methylthiazol-5-yl]butanoic acid; or 4-[2-(2-(4-(benzylthio)phenoxy)- l-oxoethyl)-4-methylthiazol-5-yl]butanoic acid; or 2-[2-(4-(3,5-dichlorobenzyloxy)phenoxy)-l-oxoethyl]benzothiazole-6-carboxylic acid; or 4-[2-(2-(4-(5-phenylpentylthio)phenoxy)- 1 -oxopropyl)-4-methylthiazol-5-yllbutanoic acid; o or 4-[2-(2-(4-(5-phenylpentylthio)phenoxy)-l-oxo-2-methyl-propyl)-4-methylthiazol-5- yI]butanoic acid; or 4-[2-(2-(4-(5-phenylpentylthio)phenoxy)-2-phenyl-l-oxyethyl)-4-methylthiazol-5- yl]butanoic acid; or 5 4-[2-(2-(4-(5-phenylpentylthio)phenoxy)-3-methyl- 1 -oxobutyl)-4-methylthiazol-5- yllbutanoic acid; or 2-[2-(4-(5-phenylpentylthio)phenoxy)- 1 -oxoethyl]benzimidazole-5-carboxylic acid; or 2-[2-[4-(5-phenylpentylthio)phenoxyl-l-oxoethyllimidazole; or 3-[2-[2-[4-(5-phenylpentylthio)phenoxyl-l-oxoethyl]-4-methylimidazol-5-yl]propenoic o acid; or 2-[2-(4-(5-phenylpentylthio)phenoxy)-l-oxoethyl]pyridine; or 4-[2-(2-(4-(5-phenylpentyloxy)phenoxy)- 1 -oxopropyl)-4-methylthiazol-5-yllbutanoic acid; or 4-[2-(2-(4-(4-chlorobenzylthio)phenoxy)- 1 -oxopropyl)-4-methylthiazol-5-yllbutanoic acid; 5 or 4-[2-(2-(4-(4-chlorobenzylthio)phenoxy)- 1 -oxobutyl)-4-methylthiazol-5-yl]butanoic acid; or or a pharmaceutically acceptable salt, enantiomer or tautomer thereof. 13. The compound according to any preceding claim for use as a pharmaceutical. 14. A pharmaceutical composition including a compound according to any one of claims 1 to 12, or a pharmaceutically acceptable salt, enantiomer or tautomer thereof, in admixture with a pharmaceutically acceptable adjuvant, diluent or carrier. 15. Use of a compound according to any one of claims 1 to 12 or a pharmaceutically acceptable salt, enantiomer or tautomer thereof, in the manufacture of a medicament, for the treatment or prophylaxis of inflammatory disease. 16. The use according to claim 15, wherein the disease is asthma. 17. A method of treating, or reducing the risk of, inflammatory disease in a patient suffering from, or at risk of, said disease, wherein the method comprises administering to the patient the compound of any one of claims 1 to 12 or a pharmaceutically acceptable salt, enantiomer or tautomer thereof. 18. The method of claim 17, wherein the disease is asthma. 19. A process for preparing the compound of any one of claims 1 to 12, or a pharmaceutically acceptable salt, enantiomer or tautomer thereof, wherein the process comprises:- (a) reacting a compound of formula IN, or a pharmaceutically acceptable salt, enantiomer or tautomer thereof, with a compound of formula N, or a pharmaceutically acceptable salt, enantiomer or tautomer thereof, wherein formulae rv and V are as defined in claim 19 or 20; or (b) reacting a compound of formula V, or a pharmaceutically acceptable salt, enantiomer or tautomer thereof, with a compound of formula NI, or a pharmaceutically acceptable salt, enantiomer or tautomer thereof, wherein formulae IN and NI are as defined in claim 19 or 20; or (c) oxidising a compound of formula XII, or a pharmaceutically acceptable salt, enantiomer or tautomer thereof, wherein formula XII is as defined in claim 19 or 21; or (d) preparing a compound of formula I, or a pharmaceutically acceptable salt, enantiomer or tautomer thereof, wherein X represents SO2, by oxidising a compound of formula I, or a pharmaceutically acceptable salt, enantiomer or tautomer thereof, wherein X represents S, and optionally after (a), (b), (c) or (d) forming a pharmaceutically acceptable salt.

Inventors: CONNOLLY STEPHEN, METE ANTONIO, CONNOLLY, STEPHEN, METE, ANTONIO
Applicants: ASTRAZENECA AB, ASTRAZENECA UK LTD, CONNOLLY STEPHEN, METE ANTONIO, ASTRAZENECA UK LIMITED, CONNOLLY, STEPHEN, METE, ANTONIO
Application year: 1999
Main classification: C07D277
IPC codes: A61K31, A61P1, A61P11, A61P17, A61P19, A61P27, A61P29, C07D213, C07D233, C07D235, C07D263, C07D277