INDOLE DERIVATIVES AS 5-HT RECEPTOR ANTAGONIST

Abstract: The invention relates to heterocyclic compounds having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of CNS disorders such as anxiety.

Description: Indol e derivatives as 5-HT receptor antagoni st This invention relates to compounds having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of CNS disorders. WO 94/04533 (SmithKline Beecham pic) describes indole and indoline derivatives which are described as possessing 5HT2C receptor antagonist activity. A structurally distinct class of compounds has now been discovered, which have been found to have 5HT2C receptor antagonist activity. Certain compounds of die invention also exhibit 5HT2B antagonist activity. 5HT2C 2B receptor antagonists are believed to be of potential use in the treatment of CNS disorders such as anxiety, depression, epilepsy, obsessive compulsive disorders, migraine, Alzheimers disease, sleep disorders, feeding disorders such as anorexia and bulimia, panic attacks, withdrawal from drug abuse such as cocaine, ethanol, nicotine and benzodiazepines, schizophrenia, and also disorders associated with spinal trauma and/or head injury such as hydrocephalus. Compounds of the invention are also expected to be of use in the treatment of certain GI disorders such as IBS as well as microvascular diseases such as macular oedema and retinopathy. The present invention therefore provides, in a first aspect, a compound of formula (I) or a salt thereof: wherein: pl and P 2 are independently phenyl, aromatic or partially saturated monocyclic or bicyclic heterocyclic rings containing up to three heteroatoms selected from nitrogen, oxygen or sulphur, A is a bond, a chain of 1 to 5 atoms optionally substituted by C 1. alkyl or A is an optionally substituted phenyl or an optionally substituted 5- to 7-membered heterocyclic ring containing up to three heteroatoms selected from nitrogen, oxygen or sulphur, R! and R 2 groups are each independently hydrogen, C g alkyl optionally substituted by NR12R13 5 C2-6 alkenyl, C2-6 alkynyl, C . alkylthio, cyano, nitro, halogen, CF3, C 2 F 5 , NR 12 R 13 , CONRl 2 R 13 , NR 12 COR 13 , S(O) NR 12 R 13 , CHO, OCF3, SCF 3 , COR 14 , CH j OR 14 , CO2R 14 or OR 14 where p is 1 or 2 and R* 2 , R 13 and R 14 are independently hydrogen, Cj.β alkyl, optionally substituted aryl or optionally substituted arylC^galkyl; n and m are independently 0, 1 or 2; R 3 is hydrogen or C j .5 alkyl; R 4 is a group of formula (i): in which: X and Y are both nitrogen, one is nitrogen and the other is carbon or a CR-5 group or one is a CR-5 group and the other is carbon or a R group; R5, R6, R7 and R8 groups are independently hydrogen, Cj.g alkyl optionally substituted by one or more fluorine atoms, C2-6 alkenyl, C3.6 cycloalkyl, C3.6 cycloalkylCi.galkoxy, C2-6 alkynyl, C3.6 cycloalkyloxy, C3.6 cycloalkyl-Cι_6 alkyl, C\.(, alkylthio, C3.6 cycloalkylthio, C3.6 cycloalkyl-Ci.g alkylthio, Cj.^alkoxy, hydroxy, halogen, nitro, OCF3, SCF3, SO2CF3, SO2F, foπnyl, C2-6 alkanoyl, cyano, optionally substituted phenyl or thienyl, NR 1 R^ ' CONR* 2 Rl 3 or CO2R 14 where where R 12 , R 13 and R 14 are as defined for R 1 ; or R 6 and R 7 form part of an optionally substituted 5- or 6-membered carbocyclic or heterocyclic ring; R and R 1 ^ are independently hydrogen or C\. alkyl; or R 4 is a group of formula (ii): (ϋ) in which X and Y are both nitrogen, one is nitrogen and the other is a CR-5 group or X and Y are both CR-5 groups and R-5, R^, R7 and R^ are as defined in formula (I); and R 1 1 is hydrogen or C\. alkyl, or R 4 is a group of formula (iii): (iii) in which R 6 , R 7 , X and Y are as defined in formula (i) and Z is O, S, CH2 or NR 15 where R 1 $ is hydrogen or C \ _6 alkyl. Cj_6 Alkyl groups, whether alone or as part of another group, may be straight chain or branched. Suitably A is a bond or a chain of 1 to 5 atoms optionally substituted by Cι_6 alkyl. Examples of such chains include (CI^) X or X(CH j ) where p is 1 to 4 and X is CO, O, S(O) x where x is 0 to 2 or A is NR, CONR, NRCO, NRCONR, CO, CH(OH), C^alkyl, CH=CH, CH=CF, CF=CF, O, S(O) x where x is 1 or 2, NR, or NRSO2 where R is hydrogen or Cj.g alkyl. Preferably A is a bond or a group CH2O, OCH 2 , or O. Suitably A is an optionally substituted phenyl group or an optionally substituted 5- or 6-membered heterocyclic ring containing up to three heteroatoms selected from nitrogen, oxygen or sulphur. Preferably A is thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, thiadiazolyl, triazolyl, pyridyl, pyrimidyl or pyrazinyl. Most preferably A is thiazolyl. Optional substituents when A is a phenyl or a heterocyclic group include those groups R* and R 2 listed above The urea moiety can be attached to a carbon or any available nitrogen atom of the ring P 2 , preferably it is attached to a carbon atom. Suitable moieties when the rings pl and P 2 are 5-membered aromatic heterocyclic rings include isothiazolyl, isoxazolyl, thiadiazolyl, oxadiazolyl and triazolyl. Suitable moieties when the rings pl and P 2 are 6-membered aromatic heterocyclic rings include, for example, pyridyl, pyrimidyl or pyrazinyl. Optional substituents for P 1 and P 2 groups include those groups R! and R 2 listed above When A is a bond, P 1 is preferably phenyl, pyridyl, pyrimidyl, pyrazinyl or pyridazinyl, preferably phenyl or pyridyl, in particular 3-pyridyl. When A is a chain of 1 to 5 atoms, P 1 is preferably phenyl or pyridyl and P 2 is preferably phenyl or pyridyl, in particular 3-pyridyl. When A is an optionally substituted phenyl group or an optionally substituted 5- or 6-membered aromatic heterocyclic ring, P is preferably phenyl or pyridyl and P 2 is preferably phenyl or pyridyl, in particular 3-pyridyl. Preferably R 1 is hydrogen or methyl. Preferably R 2 is hydrogen, halogen, methyl, CF 3 or OCF 3 . Preferably R 3 is hydrogen. .Preferably R 4 is a group of formula (i). Preferably X and Y form pan of a phenyl ring, that is to say one of X or Y is carbon and the other is a CH group or both of X and Y are CH groups. Most preferably R 4 is a group of formula (A): in which R6 and R 7 are as defined in formula (i). Suitably R^ and R 7 groups are independently hydrogen, C . alkyl optionally substituted by one or more fluorine atoms for example CF3 or C2F5, C2-6 alkenyl, C3.6 cycloalkyl, C3.6 cycloalkylCi.galkoxy, C2-6 alkynyl, C3.6 cycloalkyloxy, C3.6 cycloalkyl-Cι_6 alkyl, C . alkylthio, C3.6 cycloalkylthio, C3-6 cycloalkyl-Cι_6 alkylthio, C^galkoxy, hydroxy, halogen, nitro, CF3, C2F5, OCF3, SCF3, SO2CF3, SO2F, formyl, C2- alkanoyl, cyano, optionally substituted phenyl or thienyl, NR 12 R 13 > CONR 12 R 13 or CO2R 14 where R 12 , R 13 and R 14 are as defined for R*; or R^ and R 7 form part of an optionally substituted 5- or 6-membered carbocyclic or heterocyclic ring. Examples of such rings include cyclopentane and dihydrofuran rings. Preferably R^ is trifluoromethyl or halogen and R 7 is C\. alkoxy, in particular methoxy, Ci.^alkylthio, in particular methylthio or C 1. alkyl in particular methyl. Suitably n and m are independently 0, 1 or 2. Preferably n and m are both 1. Particular compounds of the invention include: l-[(3-Pyridyl)-3-phenyl carbamoyl]-5-methoxy-6-trifluoromethyl indoline, l-[(4-Pyridyl)-3-phenyl carbamoyl]-5-methylthio-6-trifluoromethyl indoline, l-[(3-Pyridyl)-3-phenyl carbamoyl]-5-methylthio-6-trifluoromethyl indoline, 1 -[(3-Pyridyl)-4-phenyl carbamoyl]-5-methoxy-6-trifluromethylindo_ine, l-[(4-Pyridyl)-4-phenyl carbamoyl]-5-methoxy-6- trifluoromethyl indoline, l-[(2-Pyridyl)-3-phenyl carbamoyl]-5-methoxy-6- trifluoromethyl indoline, l-[4-Methyl-3-(3-Pyridyl)-phenylcarbamoyl]-5-methoxy-6- trifluoromethyl indoline, 1 -[3-Fluoro-5-(3-pyridyl)phenylcarbamoyl]-5-methoxy-6-trifluoromethyl indoline, l-[2-Fluσro-5-(3-pyridyl) phenyl carbamoyl]-5-methoxy-6-trifluoromethyl indoline, l-(5-Phenyl pyrid-3-yl carbamoyl)-5-methoxy-6-trifluoromethyl indoline, l-(5-Phenyl pyrid -3-yl carbamoyl)-5-methylthio-6-trifluoromethyl indoline, l-[5-(3-Pyridyl)-pyrid-3-yl carbamoyl]-5-methoxy-6-trifluoromethyl indoline, l-[5-(4-Trifluoromethylphenyl)-pyrid-3-yl carbamoyl]-5-methoxy-6-trifluoromethyl indoline, l-[5-(4-Methylphenyl)-pyrid-3yl carbamoyl]-5-methoxy-6-trifluoromethyl indoline, l-[5-(2-Thienyl)-pyrid-3-yl carbamoyl]-5-methoxy-6-trifluoromethyl indoline, l-[5-(3-Thienyl)-pyrid-3-yl carbamoyl]-5-methoxy-6-trifluoromethyl indoline, l-[5-(2-Pyrrolyl)-pyrid-3-yl carbamoyl)-5-methoxy-6-trifluoromethyl indoline, l-[5-(4-Pyridyl)-pyrid-3-yl carbamoyl]-5-methoxy-6-trifluoromethyl indoline, l-[2-(3-Pyridyl)-thiazol-4-yl carbamoyl]-5-methoxy-6-trifluoromethyl indoline, l-[2-(2-Pyridyl)-thien-5-yl carbamoyl]-5-methoxy-6-trifluoromethyl indoline, l-(3-Fluoro-5-(4-methyl-3-pyridyl)phenylcarbamoyl)-5-methoxy-6- trifluoromethylindoline, l-(5-(2,6-Difluσrophenyl)-3-pvridylcaιbamoyl)-5-methoxy-6- trifluoromethylindoline, 6-Chloro-5-methyl- 1 -(4-methyl-3-(pyrid-3-yl)-phenylcarbamoyl) indoline, l-(4-Methyl-3-(pyrid-3-yl) phenylcarbamoyl)-5-thiomethyl-6-trifluoromethyl indoline, l-(3-Huoro-5-φyrid-3-yl)phenylcarbamoyl)-5-thiomethyl-6-trifluoromethyl- indoline, l-(4-CUo_x 3-(pyrid-3-yl)phenylcarbamoyl)-5-methoxy-6-trifluoromethylindoline, 5-Methoxy- 1 -(5-methyl- ( 1 ,2-4-oxadiazol- 3-yl)-phenylcarbamoyl)-6-trifluoromethyl indoline, 1 - [4-Methyl- 3- (4-methyl-3-pyridyl)phenylcarbamoy 1] -5-methoxy-6-trifluoromethyl indoline, l-[5-Bromo-3-(pyrid-3-yl)phenylcarbamoyl]-5-methoxy-6-trifluoromethylindoline, l-[4-t-Butyl-3-(pyrid-3-yl)phenylcarbamoyl]-5-methoxy-6-trifluoromethylindoline, l-[4-Methoxy-3-(pyrid-3-yl)phenylcarbamoyl]-5-methoxy-6-trifluoromethylindoline, 1 - [5-Fluσro-4-methoxy-3- (pyrid- 3-yl)phenylcarbamoyl] -5-methoxy-6- trifluoromethylindoline, 1 - [3-Bromo-4-methyl-5- (3-pyridyl)phenylcarbamoyl] -5-methoxy-6- trifluoromethylindoline, 1 -[3-(4-Isoquinolyl)phenylcarbamoyl]-5-methoxy-6-trifluoromethyl indoline, l-[5-(4-Methyl-3-pyridyl)-pyrid-3-ylcarbamoyl]-5-methoxy-6- trifluoromethylindoline, l-[6-(3-Pyridyl)-pyrid-3-ylcarbamoyl]-5-methoxy-6- trifluoromethylindoline, l-[5-(2-Furyl)-pyrid-3-ylcarbamoyl-5-methoxy-6-trifluoromethyl indoline, l-[2-(Pyrazinyl)-thiazol-4-ylcarbamoyl]-5-methoxy-6-trifluoromethyl-indθ-ine, l-[3-(5-Pyriπ_idyl)phenylcarbamoyl]-5-methoxy-6-trifluoromethyl-indoline, l-[3-(4-Methyl-3-pyridyl)phenylcarbamoyl]-5-methoxy-6-trifluoromethylindoline, l-[5-Ethyl-3-φyrid-3-yl)phenylcarbamoyl]-5-methoxy-6-trifluoromethylindoline, 5-Methoxy- 1 -[5-phenyl-3-(pyrid-3-yl)phenylcarbamoyl]-6-trifluoromethyl indoline, 6-Chloro-5-methyl-l-[4-methyl-3-(4-methyl-3-pyridyl)phenyl carbamoyl] indoline, l-[3-(pyrid-3-ylaimnoc_ubonyl)-phenylcarbamoyl]-5-memoxy-6-l_rifluoromethyl- indoline, 1 - [3-(Pyrid-3-ylaimnocarbonyl)-phenylcarbamoyl]-5-memyltMcH6-trifluoromethyl- indoline, 1 - [3- (Pyrid-4-ylaminocarbonyl)-phenylcarbamoyl] -5-methylthio-6-trifluoromethyl indoline, l-[4-(Pyrid-3-ylaminocarbonyl)-phenylcarbamoyl]-5-methylthio-6-trifluoromethyl indoline, l-[4-(Pyrid-4-ylaminocarbonyl)-phenylcarbamoyl]-5-methylthio-6- trifluoromethyl indoline, l-[3-(3-pyridylcarbonyl)phenylcarbamoyl]-5-methoxy-6- trifluoromethyl indoline, l-[3-(Pyrid-3-yl-aminosulphonyl)-phenylcarbamoyl]5-methoxy-6-trifluoromethyl- indoline, 5-Methylthio-6-trifluoromethyl- 1 -[6-(pyridin-3-yloxy)pyridin-3- ylcarbamoyl)]indoline, 5-Methoxy-6-trifluoromemyl-l-[6-(pyridin-3-yloxy)pyridin-3-ylcarbamoyl]indoline, 5-Methoxy-6-trifluoromethyl- 1 - [4-(pyridin-4-ylmethyloxy)phenyl carbamoyl]indoline, 5-Methoxy-6-trifluoromethyl- 1 -[6-(pyridin-4-ylmethyloxy)pyridin-3- ylcarbamoyl] indoline, 5-Methylthio-6-trifluoromethyl- l-[4-(pyrid-4-yl-methylamino carbonyl)phenyl carbamoyl] indoline, Trans-5-Medιylthio-6-trifluoromethyl- 1 - { 4- [2-ethenyl-(4-pyridyl)] -phenyl carbamoyl } -indoline, 5-Methylthio-6- trifluoromethyl- 1 - { 4- [2-ethy l(4-pyridyl)]phenyl carbamoyl } indoline, l-(l-(4-Pyridyl)-5-indolylcarbamoyl)-5-methoxy-6-trifluoromethylindoline, 5-Methoxy-6-trifluoromethyl-l-[4-(pyridin-4-yltiιiomethyl)phenyl carbamoyl] indoline, 5-Methoxy-6-trifluoromethyl- 1 -[4-(pyridin-4-ylsulphonylmethyl) phenylcarbamoyl] indoline, 5-Methoxy-6-trifluoromethyl- 1 -[4-(pyridin-4-ylmethylthio)phenyl carbamoyl]indoline, 5-Methylthio-6-trifluoromethyl-l-[(6-phenoxy)-3-pyridylcarbamoyl]-indoline, 5-Methoxy-6^trifluoromemyl-l-[2-(pyridin-3-yloxy)pyridin-4-ylcarbamoyl)]indoline, 5-Methylthio-6-trifluoromethyl- 1 -[6-(2-methylpyridin-3-yloxy) pyridin-3- ylcarbamoyl]indoline, 5-Methylthio-6-trifluoromethyl- 1 -[6-(6-methylpyridin-3-yloxy)pyridin-3- ylcarbamoyl] indoline, 5-Methoxy-6-trifluoτomethyl- 1 -[6-(pyridin-3-ylthio)pyridin-3-ylcarbamoyl]indoline, 5-Methylthio-6-trifluoromethyl- 1 -[4-(p * yrid-3-ylmethyl)amido phenyl carbamoyl]indoline, 5-Methylthio-6-trifluoromethyl- 1 -[3-(pyrid-4-ylmethyl) amidophenylcarbamoyl] indoline, 5-Methylthio-6-trifluoromethyl-l-[4-(pyrid-2-ylmethyl) amidophenylcarbamoyl] indoline, 1 -( 1 -(3-Pyridylmethyl)-5-indolylcarbamoyl)-5-methoxy-6- trifluoromethylindoline, 1 - ( 1 - (4-Pyridylmethyl)-5-indolylcarbamoyl)-5-methoxy-6- trifluoromethylindoline, l-(l-(3-pyridyl)-5-indolylcarbamoyl)-5-methoxy-6- trifluoromethyl indoline, 5-Methylthio-6-trifluoromethyl- 1 - { 3-[2-(3-pyridyl)thiazol-4-yl]phenylcarbamoyl } indoline, 5-Methylthio-6-trifluoromethyl-l-{4-[2-(4-pyridyl)-thiazol-4-yl]phenyl carbamoyl } indoline, 5-Methylthio-6-trifluoromethyl- 1 - { 4-[2-(3-pyridyl)-thiazol-4- yl]phenylcarbamoyl) indoline, l-[4-Fluoro-3-(3-pyridyl)phenylcarbamoyl]-5-methoxy-6- trifluoromethyl indoline, l-[3-Ruoro-5-(pyrimidin-5-yl)phenylcarbamoyl]-5-methoxy-6- trifluoromethyl indoline, l-[4-Chloro-3-(4-methyl-3-pyridyl)phenylcarbamoyl]-5-methoxy-6- trifluoromethylindoline, l-[2,3-Dihydro-7-(pyrid-3-yl)benzofuran-5-ylcarbamoyl]-5-methoxy-6- trifluoromethyl indoline, 5-Methoxy-6-trifluoromethyl- 1 -[6-(2-methylpyridin-3-yloxy)pyridin-3- ylcarbamoyl]indoline, 5-Methoxy-6-trifluoromethyl- 1 -[6-(4-methylpyridin-3-yloxy)pyridin-3- ylcarbamoyl]indoline, and pharmaceutically acceptable salts thereof. Further preferred compounds are those of examples 83 - 177 and pharmaceutically acceptable salts thereof. The compounds of die formula (I) can form acid addition salts with acids, such as conventional pharmaceutically acceptable acids, for example maleic, hydrochloric, hydrobromic, phosphoric, acetic, fumaric, salicylic, citric, lactic, mandelic, tartaric and methanesulphonic. Preferred salts are mesylate salts. Compounds of formula (I) may also form N-oxides or solvates such as hydrates, and the invention also extends to these forms. When referred to herein, it is understood that the term 'compound of formula (I)' also includes these forms. Certain compounds of formula (I) are capable of existing in stereoisomeric forms including enantiomers and the invention extends to each of these stereoisomeric forms and to mixtures thereof including racemates. The different stereoisomeric forms may be separated one from the other by the usual methods, or any given isomer may be obtained by stereospecific or asymmetric synthesis. The invention also extends to any tautomeric forms and mixtures thereof. The present invention also provides a process for the preparation of a compound of formula (I) or a pharmaceutically acceptable salt thereof, which process comprises: (a) the coupling of a compound of formula (II); (π) with a compound of formula (HI); D-R 4 ' (IH) wherein A, P 1 and P 2 are as defined in formula (I) , C and D contain the appropriate functional group(s) necessary to form the moiety -NR 3 CO when coupled, die variables R 1 , R 2 , R 3 and R 4 are R 1 , R 2 , R 3 and R 4 respectively, as defined in formula (I), or groups convertible thereto, and tiiereafter optionally and as necessary and in any appropriate order, converting any R ' , R 2' , R 3 ' and R 4 , when oti er than R 1 , R 2 , R 3 and R 4 respectively to R 1 , R 2 , R 3 and R 4 , interconverting R 1 , R 2 , R 3 and R 4 and forming a pharmaceutically acceptable salt thereof; or (b) the coupling of a compound of formula (TV); with a compound of formula (V); (V) wherein P 1 , P 2 , R 1 , R 2 , R 3 and R 4' are as defined above and E and G contain the appropriate functional group(s) necessary to form the A moiety when coupled and diereafter optionally and as necessary and in any appropriate order, converting any R 1 ', R 2' , R 3' and R 4' , when other than R 1 , R 2 , R 3 and R 4 respectively to R 1 , R 2 , R 3 and R 4 , interconverting R 1 , R 2 , R 3 and R 4 and forming a pharmaceutically acceptable salt. Suitable examples of groups C and D include: (i) C is -N=C=O and D is hydrogen, (ϋ) C is -NR 3 'COL and D is hydrogen, (iii) C is -NHR 3' and D is COL, or (iv) C is halogen and D is -CONHR 3 ' wherein R 3 ' is as defined above and L is a leaving group. Examples of suitable leaving groups L include halogen such as chloro, bromo, imidazole, phenoxy or phenylthio optionally substituted, for example, with halogen. Suitable examples of a group R 2 ' which are convertible to R 2 , include alkoxycarbonyl and benzyloxy orp__r__-methoxybenzyloxy which are converted to the group where R 2 is hydroxy using conventional conditions. Interconversions of R 1 , R 2 and R 3 are carried out by conventional procedures. For example R* halo can be introduced by selective halogenation of the ring pl using conventional conditions. It should be appreciated that it may be necessary to protect any R 1 to R 3 hydrogen variables which are not required to be interconverted. Suitable protecting groups and memods for their attachment and removal are conventional in the art of organic chemistry, such as those described in Greene T.W. "Protective groups in organic synthesis' New York, Wiley (1981). Compounds of formula (H) and (III) may be prepared according to known methods or analogous to known methods, for example using the procedures described in WO 95/01976. Compounds of formula (II) in which C is NH j , NO 2 or CO 2 H can be prepared by reacting a compound of fomula (VI) with a compound of formula (VII): (vi) (vπ) in which R 1 , R 2 , P 1 and P 2 are as defined in formula (ϋ) and T and Q contain the apppropriate functional groups necessary to form the A group. For example a) when A is a bond, one of T and Q is B(OH) 2 or Sn(Bu) 3 and the other is halogen or OTf (see for example Adv. Het. Chem. 1995, i&, 306). b) when A is a chain, one of T and Q is an acid chloride and the other is amino, or one of T and Q is hydroxy and the other is chloro or chloromethyl; or c) when A is a heterocyclic ring, one of T and Q is a dύoamide group and the other is BrCI^C-O. Compounds of formula (III) may be prepared according to known methods or analogous to known methods, for example a) from the appropriate aniline via indole formation (Nordlander [JOC, 1981, 778] or Sundberg [JOC 1984, 249] routes) followed by reduction of d e indole ring using sodium cyanoborohydride. It will be appreciated that in certain cases a mixture of indoles will be formed which can be separated at this stage or at a later stage. b) from the appropriate ortho-methyl nitrobenzene via indole formation (Leimgruber procedure Org Syn Coll vol VII, p34) followed by reduction of die indole ring. c) by aromatic substitution of a suitably protected indole/indoline precursor, for example alkylthio groups maybe introduced by thiocyanation of the indoline ring followed by hydrolysis and alkylation, or d) From d e appropriate nitrobenzene via indole formation by aromatic nucleophilic substitution (J.Med. Chem. 1990, 2089) followed by reduction of die indole using NaCNBH3. Novel intermediates of formula (HI) also form part of the invention. Suitable examples of reactions of compounds of formulae (IV) and (V) are those where E and G are the same as T and Q respectively in compounds of formulae (VI) and (VII) above. Compounds of formula (TV) are commercially available or can be prepared using standard procedures. Compounds of formula (V) can be prepared using standard procedures such as diose outlined in WO 94/04533 or WO 95/01976. Pharmaceutically acceptable salts may be prepared conventionally by reaction witii the appropriate acid or acid derivative. N-oxides may be formed conventionally by reaction witii hydrogen peroxide or percarboxylic acids. Compounds of formula (I) and their pharmaceutically acceptable salts have HT2B 2C receptor antagonist activity and are believed to be of potential use fo the treatment or prophylasis of CNS disorders such as anxiety, depression, epilepsy, obsessive compulsive disorders, migraine, Alzheimers disease, sleep disorders, feeding disorders such as anorexia and bulimia, panic attacks, withdrawal from drug abuse such as cocaine, ethanol, nicotine and benzodiazepines, schizophrenia, and also disorders associated with spinal trauma and/or head injury such as hydrocephalus. Compounds of die invention are also expected to be of use in the treatment of certain GI disorders such as IBS as well as microvascular diseases such as macular oedema and retinopathy. Thus the invention also provides a compound of formula (I) or a pharmaceutically acceptable salt thereof, for use as a therapeutic substance, in particular in die treatment or prophylaxis of the above disorders. The invention further provides a method of treatment or prophylaxis of the above disorders, in mammals including humans, which comprises administering to die sufferer a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof. In another aspect, the invention provides d e use of a compound of formula (I) or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for the treatment or prophylaxis of the above disorders. The present invention also provides a pharmaceutical composition, which comprises a compound of formula (I) or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. A pharmaceutical composition of die invention, which may be prepared by admixture, suitably at ambient temperature and atmospheric pressure, is usually adapted for oral, parenteral or rectal administration and, as such, may be in the form of tablets, capsules, oral liquid preparations, powders, granules, lozenges, reconstitutable powders, injectable or infusable solutions or suspensions or suppositories. Orally administrable compositions are generally preferred. Tablets and capsules for oral administration may be in unit dose form, and may contain conventional excipients, such as binding agents, fillers, tabletting lubricants, disintegrants and acceptable wetting agents. The tablets may be coated according to mediods well known in normal pharmaceutical practice. Oral liquid preparations may be in the form of, for example, aqueous or oily suspension, solutions, emulsions, syrups or elixirs, or may be in the form of a dry product for reconstitution wid water or other suitable vehicle before use. Such liquid preparations may contain conventional additives such as suspending agents, emulsifying agents, non-aqueous vehicles (which may include edible oils), preservatives, and, if desired, conventional flavourings or colourants. For parenteral administration, fluid unit dosage forms are prepared utilising a compound of die invention or pharmaceutically acceptable salt thereof and a sterile vehicle. The compound, depending on die vehicle and concentration used, can be either suspended or dissolved in the vehicle. In preparing solutions, the compound can be dissolved for injection and filter sterilised before filling into a suitable vial or ampoule and sealing. Advantageously, adjuvants such as a local anaesthetic, preservatives and buffering agents are dissolved in the vehicle. To enhance the stability, the composition can be frozen after filling into the vial and die water removed under vacuum. Parenteral suspensions are prepared in substantially d e same manner, except that the compound is suspended in die vehicle instead of being dissolved, and sterilization cannot be accomplished by filtration. The compound can be sterilised by exposure to etiiylene oxide before suspension in a sterile vehicle. Advantageously, a surfactant or wetting agent is included in the composition to facilitate uniform distribution of die compound. The composition may contain from 0.1% to 99% by weight, preferably from 10 to 60% by weight, of the active material, depending on die method of administration. The dose of die compound used in die treatment of the aforementioned disorders will vary in the usual way with the seriousness of the disorders, die weight of die sufferer, and odier similar factors. However, as a general guide suitable unit doses may be 0.05 to 1000 mg, more suitably 0.05 to 20.0 mg, for example 0.2 to 5 mg; and such unit doses may be administered more than once a day, for example two or three a day, so tiiat the total daily dosage is in the range of about 0.5 to 100 mg; and such therapy may extend for a number of weeks or months. When administered in accordance witii the invention, no unacceptable toxicological effects are expected witii the compounds of die invention. The following Descriptions and Examples illustrate the preparation of compounds of die invention. Description 1 6-TrifluoromethyIindoline (Dl) 6-Trifluoromethylindole 1 (5.27g, 28.5 mmol) in glacial acetic acid (50 ml) was treated widi sodium cyanobσrohydride (3.60g, 57.0 mmol) portionwise at room temperature with stirring. After 3 h at room temperature the reaction mixture was diluted widi water (100 ml) and basified widi 40% aqueous NaOH widi cooling. The mixture was then extracted with dichloromethane (3 x 150 ml) and die combined extracts were dried (Na2SO_ ) and evaporated to give the tide compound (4.83g, 91%) as a brown solid. ■■ Η NMR (CDC1 3 ) δ: 3.07 (2H, t, J = 8), 3.62 (2H, t, J = 8), 6.80 (1H, s), 6.92 (1H, d, J = 8), 7.15 (lH, d, J = 8). 1. A.N. Tischler and TJ. Lanza, Tet. Lett. 1986, 26, 1653. Description 2 5-Th.ocyanato-6-trifluoromethyIindoIine (D2) A mixture of 6-trifluoromedιylindoline (Dl) (9.7g, 52 mmol) and potassium thiocyanate (10.09g, 104 mmol) in methanol (200 ml) was treated widi a solution of bromine (2.82 ml, 55 mmol) in methanol (35 ml) drop wise over 0.5 h at -5-0°C. The reaction mixture was allowed to warm to room temperature and stirred overnight then evaporated to dryness. The residue was partitioned between aqueous K2CO3 (100 ml) and dichloromethane (3 x 100 ml). The combined extracts were dried (Na2SO4) and evaporated and die residue chromatographed on silica using 2-30% ethyl acetate/petroleum etiier as eluant to afford die title compound (9.1g, 72%) as a yellow solid. l H NMR (CDCI3) δ: 3.12 (2H, t, J = 8), 3.72 (3H, t, J = 8), 4.23 (1H, br s), 6.89 (1H, s), 7.50 (1H, s). Description 3 Di[5-(6-trifluoromethylindolinyl)]disuIphide (D3) The thiocyanate (D2) (28.5g, 0.116 mol) in dioxane (200 ml) and water (100 ml) was treated widi aqueous ammonia (880, 200 ml) at 90° C for 1 h. The mixture was cooled and evaporated to give a residue which was partitioned between water (300 ml) and dichloromethane (4 x 300 ml). The combined extracts were dried (Na2SO4) and evaporated to give die titie compound (25.5g, 100%) as a yellow solid. IH NMR(CDC1 3 ) δ: 3.03 (2H, t, J = 8), 3.67 (2H, t, J = 8), 4.00 (IH, br s), 6.80 (IH, s), 7.49 (IH, s). Description 4 Di-[5-(l-acet l-6-trinuoromethylindolinyl)]disulphide (D4) The disulphide (D3) (26g, 0.119 mol) in dichloromethane (300 ml) and triethylamine (47.3 ml, 0.339 mol) was treated dropwise widi a solution of acetic anhydride (22.5 ml, 0.238 mol) in dichloromethane (50 ml) at 0° C. The mixture was allowed to warm to room temperature, stirred for 1 h then poured into 2.5 M aqueous HC1 (400 ml). The organic layer was separated and d e aqueous was further extracted widi dichloromethane (200 ml). The combined organic extracts were dried (Na2SO4) and evaporated to give the tide compound (29. lg, 94%) as a yellow solid. *H NMR (CDC1 3 ) δ: 2.22 (3H, s), 3.21 (2H, t), 4.10 (2H, t), 7.68 (IH, s), 8.47 (IH, s). Description 5 l-Acetyl-5-mercapto-6-trifluoromethylindoline (D5) A mixture of the diacetyl disulphide (D4) (28.5 g, 54.8 mmol), triphenylphosphine (20.85g, 79.5 mmol) and cone, aqueous HC1 (1 ml) in dioxane (300 ml) and water (75 ml) was heated at reflux for 1.5 h. The reaction mixture was cooled and evaporated to a residue which was partitioned between dichloromethane (300 ml) and 1% aqueous NaOH (300 ml). The organic phase was further extracted widi 1% aqueous NaOH (200 ml) and die combined aqueous fractions carefully acidified and extracted widi dichloromethane (3 x 300 ml). The combined organic extracts were dried (Na2SO4) and evaporated to afford the tide compound (26g, 91%) as a yellow solid. -1H NMR (CDCI3) δ: 2.24 (3H, s), 3.20 (2H, t), 3.68 (IH, m), 4.11 (2H, t), 7.22 (IH, s), 8.51 (lH, s). Description 6 l-Acetyl-5-methylthio-6-trifluoromethyiindoline (D6) A mixture of the thiol (D5) (26g, 99 mmol), anhydrous K2CO3 (15.12 g, 109 mmol) and iodomethane (18.6 ml, 300 mmol) in dry DMF (100 ml) was heated at 80° C for 1 h. The reaction mixture was cooled, evaporated in vacua and partitioned between water (200 ml) and dichloromethane (3 x 200 ml). The combined organics were washed widi water (400 ml), dried (Na2SO4) and evaporated to yield the tide compound (26.3g, 97%) as a yellow oil. !H NMR (CDCI3) δ: 2.22 (3H, s), 2.49 (3H, s), 3.24 (2H, t, J = 8), 4.12 (2H, t, J = 8), 7.23 (IH, s), 8.51 (IH, s). Description 7 5-Methvlthio-6-trifluoromethγlindoline (D7) Method (a) The acetyl indoline (D6) (26.3g, 95 mmol) was treated with NaOH (30g, 750 ml) in water (150 ml) and ethanol (200 ml) at reflux for 1.5 h. The reaction mixture was cooled, diluted with water (200 ml) and most of die etiianol evaporated in vacuo. The remaining mixture was extracted widi dichloromethane (3 x 200 ml) and die combined extracts were dried (Na2SO4) and evaporated to afford die tide compound (21.9g, 99%) as a yellow oil. -1H NMR (CDCI3) δ: 2.41 (3H, s), 3.07 (2H, t), 3.63 (2H, t), 3.90 (IH, br s), 6.88 (IH, s), 7.30 (IH, s). Method (b) A stirred solution of potassium thiocyanate (38.6g, 0.39 mol) in methanol (470 ml) at -2° C under argon was treated dropwise over 10 minutes with bromine (10.3 ml, 0.195 mol) giving a yellow precipitate. The reaction mixture was stirred at 0° C for a further 15 minutes, then treated witii a solution of 6-trifluoromethylindoline (Dl) (33.2g, 0.177 mol) in methanol (320 ml) and allowed to warm to room temperature and stir for 4 h. A solution of potassium hydroxide (49.5g, 0.88 mol) in water (300 ml) was added in one portion, causing die temperature to rise to 43° C and a brown solution to be produced. The mixture was stirred at 43-45° C for 25 minutes, then cooled to 12° C and treated widi iodomediane (10.9 ml, 0.177 mol). The resulting mixture was allowed to warm to room temperature and stirred for 1.5 h, then concentrated in vacuo to approx. 350 ml volume. The residual aqueous mixture was extracted widi dichloromediane (2 x 400ml) and die combined extract dried (Na2SO4) and concentrated in vacuo to give a brown oil (43 g), which was chromatographed on silica gel eluting with dichloromethane to afford die title compound (D7) as a light brown solid (25.3g, 61%) widi spectral properties identical to diose described above. Description 8 l-Methoxy-4-nitro-2-trifluoromethylbenzene (D8) Sodium (11.78g, 0.512 mol) was dissolved in dry methanol (1 1) and to die resulting solution was added a solution of l-chloro-4-nitro-2-trifluoromethyl-benzene (96.22g, 0.427 mol) in methanol (100 ml). The reaction mixture was refluxed for 3 h then cooled and evaporated in vacuo. The residue was partitioned between water (500 ml) and dichloromediane (3 x 400 ml). The combined organic extracts were dried (Na2SO4) and evaporated to give the title compound (93.76g, 99%) as a white solid. l H NMR (CDCI3) δ: 4.05 (3H, s), 7.12 (IH, d), 8.45 (IH, dd), 8.52 (IH, d). Description 9 (5-Methoxy-2-nitro-4-trifluoromethylphenyl)acetonitriIe (D9) A mixture of l-methoxy-4-nitro 2-trifluoromethylbenzene (D8) (93g, 0.421 mol) and 4-chlorophenoxyacetonitrile (77.55g, 0.463 mol) in dry DMF (500 ml) was added dropwise over 0.75 h to a stirred solution of KO l Bu (103.85g, 0.927 mol) in dry DMF (400 ml) at -10° C. After complete addition die resulting purple solution was maintained at -10° C for 1 h tiien poured into a mixture of ice/water (1.5 1) and 5 M aqueous HCl (1.5 1). The resulting mixture was extracted widi dichloromethane (3 x 1 1). The combined extracts were washed widi water (3 1), dried (Na2SO4) and evaporated under reduced pressure. The residue was chromatographed on silica using 10-40% ethyl acetate/petroleum ether as eluant to give the crude product which was recrystallised from ethyl acetate/petroleum ether to afford d e tide compound (85.13g, 78%) as a white solid. Mp 103- 104 °C. l H NMR (CDCI3) δ: 4.10 (3H, s), 4.37 (2H, s), 7.34 (IH, s), 8.53 (IH, s). Description 10 5-Methoxy-6-trifluoromethyHndole (D10) (5-Medιoxy-2-nitro-4-trifluoromethylphenyl)acetonitrile (D9) (85g, 0.327 mol) in ethanol water (9:1, 1.6 1) and glacial acetic acid (16 ml) was hydrogenated over 10% palladium on carbon (50 g) at 50 psi for 0.5 h at room temperature. The reaction mixture was filtered and evaporated in vacuo. The residue was partitioned between aqueous K2CO3 (1 1) and dichloromediane (2 x 1 1) and die combined organic extract was dried (Na2SO4) and evaporated to afford die tide indole (67.63g, 96%) as a grey solid. *H NMR (CDCI3) δ: 3.94 (3H, s), 6.53 (IH, m), 7.21 (IH, s), 7.32 (IH, m), 7.64 (lH, s), 8.25 (lH, br s). Description 11 5-Methoxy-6-trifluoromethyIindoline (Dll) The indole (D10) (67.63g, 0.315 mol) was treated widi sodium cyanoborohydride (40 g, 0.637 mol) in glacial acetic acid (500 ml) as in the metiiod of Description 1 to afford the tide indoline (67.73g, 99%) as an off-white solid. *H NMR (CDCI3) δ: 3.07 (2H, t), 3.58 (2H, t), 3.67 (IH, br s), 3.83 (3H, s), 6.83 (IH, s), 6.88 (IH, s). Description 12 3-(4-Pyridyl) aniline (D12) 3-Bromoaniline (0.24 ml, 2.2 mmol) and sodium carbonate (0.70g, 6.6 mmol) were suspended in a mixture of 1,2-dimetiιoxyetiιane (16 ml) and water (4 ml). The reaction mixture was then treated widi 4-pyridyl boronic acid (0.27g, 2.2 mmol), and flushed widi Argon. Tetrakis (triphenylphosphine)-palladium (0) (0.35g) was then added, and d e mixture was heated to reflux under Argon for 24 hours. The reaction mixture was allowed to cool after which it was partitioned between dichloromethane and water. The aqueous layer was again extracted widi dichloromethane. The combined extracts were then dried (Na2SO4) and concentrated in vacuo to afford a pale yellow solid (0.35g). This was chromatographed on silica gel eluting with ethyl acetate to afford die title compound as a white solid (0.15g, 41%). ^ NMR (200 MHz, CDCI3) δ(ppm): 8.63 (dm, 2H), 7.45 (dm, 2H), 7.35 (t, IH), 7.0 (dm, IH), 6.91(m, IH), 6.75 (dm, IH), 3.75 (b, 2H) Description 13 3-(3-Pyridyl)aniline (D13) A mixture of 3-bromopyridine (2.9ml, 4.74g, 30mmol), 3-aminophenyl boronic acid (4.63g, 30mmol), sodium carbonate (lOg, 90mmol) and tetrakis (triphenylphosphine) palladium (0) (0.9g) in 1, 2-dimethoxyethane - water (150ml - 50ml) was heated to reflux under argon for 12h. The mixture was concentrated tiien partitioned between ethyl acetate/dilute brine. The organic extract was dried and evaporated affording a brown gum (6g). Chromatography on silica eluting with 50% ethyl acetate - 60/80 petroleum ether then ethyl acetate afforded die product as a yellow crystalline solid (4.8g, 95%). !H NMR (200MHz, CDCI3) 3.8 (2H, 6s), 6.70 (IH, dm), 6.85 (IH, m), 6.95 (IH, m), 7.25 (IH, t), 7.35 (IH, m) 7.85 (IH, m), 8.60 (IH, dd), 8.85 (IH, d). Description 14 l-(5-Bromo-pyrid-3-yl carbamoyI)-5-methoxy-6-trifluromethyl-indoline (D14) A solution of 5-bromo-pyrid-3-yl acyl azide (3.16g, 13.9 mmol) in toluene (500ml) was heated to reflux under argon for lh. The solution was allowed to cool to room temperature then added to a solution of 5-med oxy-6-trifluoro-methyl indoline (2.7g, 12.5mmol) in dichloromediane (200ml). The mixture was set aside in the fridge for lh, then filtration and drying afforded d e tide compound as a white solid (4.62g, 89%), mp 220-222°C. l H NMR (D6. DM SO) 3.30 (2H, t, J), 3.85 (3H, S), 4.20 (2H, t), 7.20 (IH, S), 8.10 (IH, S), 8.35 (2H, m), 8.75 (IH, S), 8.95 (IH, S). Description 15 2-(3-Pyridyl)-thiazole-4-carbonyl azide (D15) A suspension of 2-(3-pyridyl)-dιiazole-4-carboxylic acid (0.824g, 4mmol) in dichloromethane-chloroform (30ml- 15ml) was treated widi triethylamine (0.75ml, 0.5g, 5mmol) and tiien iso-butyl chloroformate (0.65ml, 0.68g, 5mmol). After lh the mixture was evaporated to dryness and die residue suspended in THF (30ml) and a solution of sodium azide (0.46g, 7mmol) in water (10ml) was added. After lh, the mixture was concentrated (rotary evaporator) and partitioned between dichloromediane and brine. The organic extract was washed widi half- saturated brine, dried, and evaporated. Trituration with petroleum ether, filtration, and drying in vacuo (CAUTION - no heating) afforded die tide compounds as a brown solid (0.37g, 40%). Description 16 2-(2-Pyridyl)-thiophene-5-carbonyl azide (D16) This was prepared in 45% yield by die same metiiod as for Description 15. Description 17 l-(3-Fluoro-5-iodophenylcarbamoyl)-5-methoxy-6-trifluoromethylindoline (D17) A mixture of 3-fluoro-5-iodoaniline (0.47g, 1.98 mmol) and l,l'-carbonyl diimidazole (0.33g, 2 mmol) in dichloromethane (40 ml) was stirred at room temperature for 1 h, then evaporated to dryness. To die residue was added dimediylforma ide (DMF, 10 ml) and a solution of 5-methoxy-6- trifluoromethylindoline (Dl 1, 0.44g, 2 mmol) in DMF (5 ml). The mixture was heated at 80°C overnight, then cooled and poured into water. The precipitate was filtered off, washed widi water and dried. The crude product was chromatographed on silica gel and eluted wid dichloromediane. Eluted product was recrystallised from dichloromethane to give the tide compound (0.38g, 40%), Mp. 221-4°C. !H NMR (d^MSO) δ: 3.27 (2H, t, J=8), 3.84 (3H, s), 4.15 (2H, t, J=8), 7.20 (IH, s), 7.27 (IH, d, J=7), 7.57 (IH, d, J=12), 7.84 (IH, s), 8.10 (IH, s), 8.78 (IH, s). MS (El) m/z = 480 (M * ), C-^^O^I requires M=480 Description 18 Ethyl 5-(2,6-difluorophenyI)nicotinate (D18) A mixture of (2,6-difluorophenyl)tributyltin ( 1.18g, 2.9 mmol), ethyl 5- bromonicotinate (0.69g, 3 mmol) and tetrakis (triphenylphosphine) palladium (0) (0.1 Og) in xylene (10 mL) was heated under reflux for 24h, then cooled, filtered and evaporated. The residue was chromatographed on silica gel eluted widi 20% ethyl acetate/petrol to give the tide compound (0.64g, 84%). iH NMR (CDCl,) δ: 1.43 (3H, t, J=7), 4.44 (2H, q, J=7), 7.06 (2H, t, J=7), 7.39 (IH, quintet, J=7), 8.42 (IH, s), 8.88 (IH, s), 9.23 (IH, s) MS (API): m/z=264 (MIT), C it U__N0^ 2 requires M+l = 264 Description 19 5-(2,6-Difluorophenyl)nicotinoyl hydrazide (D19) A mixture of ester (D18, 0.64g, 2.4 mmol) and 98% hydrazine hydrate (1 mL) in methanol (10 mL) was heated under reflux overnight, then cooled in ice. The precipitate was filtered off. The filtrate was evaporated and die residue was triturated widi water before combining widi die initial precipitate. The crude product was washed widi eti er and dried in vacuo to give the tide compound (0.50g, 84%). ^ NMR (d 6 DMSO) δ: 4.60 (2H, s), 7.29 (2H, t, J=7), 7.57 (IH, quintet, J=7), 8.28 (IH, s), 8.80 (IH, s), 9.03 (IH, s), 10.05 (IH, s). MS (API): m/z = 250 (MH * ), C I2 H,N,OF 2 requires M+l = 250 Description 20 5-(2,6-Difluorophenyl)nicotinoyl azide (D20) To a suspension of hydrazide (D19, 0.50g, 1.99 mmol) in concentrated hydrochloric acid (3 mL) and water (2 mL) at -5°C was added dropwise a solution of sodium nitrite (0.14g, 2.0 mmol) in water (2 ml). The mixture was stirred at -5°C for 0.5 h, then a solution of potassium carbonate (2.3g) in water (25 ml) was added cautiously. The precipitate was filtered off, washed widi water and dried in vacuo at room temperature to give the title compound (0.48g, 93%). !H NMR (CDC1 3 ) δ: 7.05 (2H, t, J=7), 7.40 (IH, quintet, J=7), 8.41 (IH, s), 8.93 (IH, s), 9.22 (IH, s) MS (API) 261 (MIT), 233 (MH * -N 2 ) Description 21 Phenyl N-(3-Bromo-5-(pyrid-3-yl)phenyl)carbamate (D21) The tide compound was prepared from 3-Bromo-5-(pyrid-3-yl)aniline using the method of Description 67. *H NMR 250MHz CDCI 3 δ: 7.1-7.9 (m, 9H), 8.6-8.7 (br, IH, Ar), 8.8-8.9 (br, IH, Ar) Description 22 Phenyl N-[4-t-But l-3-(pyrid-3-yI)phenyl]carbamate (D22) The tide compound (0.18g, 68%) was prepared from 4-t-butyl-3-(pyrid-3-yl)aniline (0.175g, 0.00077 mole) using the metiiod of Description 67. Η NMR (200 MHz, CDC1,) δ: 1.18 (9H, s), 7.02-7.65 (1 IH, m), 8.49-8.62 (2H,m) Description 23 Phenyl N-[4-Methoxy-3-(pyrid-3-yl)phenyl]carbamate (D23) The tide compound (0.48g, 75%) was prepared from 4-methoxy-3-(pyτid-3-yl)aniline (0.40g, 0.002 mole) using the metiiod of Description 67. 'H NMR (200 MHz, CDC1,) δ: 3.80 (3H, s), 6.90-7.57 (10H, m), 7.88 (IH, dt), 8.56 (lH, dd), 8.78 (lH, d) Description 24 Phenyl N-[5-Fluoro-4-methoxy-3-(pyrid-3-yI)phenyI]carbamate (D24) The title compound (0.48g, 79%) was prepared from 5-fluoro-4-methoxy-3-(pyrid-3- yl)aniline (0.40g, 0.0018 mole) using the metiiod of Description 67. l H NMR (200 MHz, CDC1,) δ: 3.75 (3H, s), 7.01-7.67 (8H, m), 7.82-8.08 (2H, m), 8.64 (IH, d), 8.80 (IH, s). Description 25 l-(3 -Dibromo-4-methylphenylcarbamoyl)-5-methoxy-6- trifluoromethylindoline (D25) The tide compound was prepared by die metiiod of Example 1, from 3,5-dibromo-4- methylaniline (2.64g, 10 mmol), Ll'-carbonyldiimidazole (1.64g, 10 mmol) and 5- methoxy-6- trifluoromethylindoline (Dl 1) (2.2g, 10 mmol). Crude product was recrystallised from DMSO/water and washed witii medianol and ether, to give the tide compound (2.64g, 52%), mp >250°C. NMR (d 6 -DMSO) δ: 2.43 (3H, s), 3.26 (2H, t, J=8), 3.84 (3H, s), 4.14 (2H, t, J=8), 7.20 (IH, s), 7.96 (2H, s), 8.10 (IH, s), 8.72 (IH, s). MS (API) 507 (MH\ "Br , 509 (MIT, 7, Br ΪJ Br), 511 (MH * , "Br^ Description 26 l-[5-Bromo-(3-pyridylcarban*ιoyl)]-5-methoxy-6-trifluoromethyl indoline (D26) 5-Bromo-3-pyridylcarbonylazide (3.7g, 16 mmoles) was heated under reflux in dry toluene (100 ml) for 1 hr. After cooling die resulting solution of isocyanate was treated widi a solution of 5-methoxy-6- trifluoromethyl indoline (Dl 1) (3.5g, 16 mmoles) in dichloromediane (600 ml) and stirred overnight. The mixture was concentrated in vacuo and the residue triturated with dietiiyl edier. Filtration and washing with more dietiiyl ether gave die title compound (D26) (5.4g, 81%). • 1H NMR (DMSO-d 6 ) δ: 3.30 (2H, t, J=8Hz), 3.83 (3H, s), 4.18 (2H, t, J=8Hz), 7.20 (IH, s), 8.10 (IH, s), 8.30-8.35 (IH, m), 8.71 (IH, s), 8.92 (IH, s) Description 27 Phenyl N-[6-(Pyrid-3-yl)pyrid-3-yl]carbamate (D27) The title compound was prepared as in die method of description 67 from die corresponding aniline. This gave the tide compound (0.66g, 100%) M.S. (API) found m/z 292 (MH * ), C 17 H.,N,O 2 requires 292 Description 28 Phenyl-N-[3-(4-methylpyrid-3-yl)phenyl]carbamate (D28) The title compound was prepared as in the metiiod of description 67 from die corresponding aniline. This gave the title compound (0.8g, 100%) NMR (CDC1,) δ: 2.29 (3H, s), 7.10-7.40 (11H, m), 8.42-8.49 (2H, m) Description 29 3-(5-Pyrimidy!)-aniline (D29) This was prepared from 5-bromopyrimidine and 3-aminophenyl boronic acid in 84% yield by d e same method as for Description 12. Η NMR (CDCl,) 3.80 (2H, bs), 6.80 (IH, dd), 6.90 (IH, m), 7.00 (IH, d), 7.30 (2H, m), 8.95 (2H, s), 9.20 (IH, s). Description 30 Phenyl N-[3-ethyl-5-(pyrid-3-yI)phenyI]carbamate (D30) The title compound (0.276g, 0.87 mmol) was prepared by die methodology of description 67, using 3-ethyl-5-(pyrid-3-yl)aniline, phenyl chloroformate (0.13ml, 0.96 mmol) and triethylamine (0.13ml, 0.96 mmol) in dichloromediane (10 ml) !H NMR 250 MHz CDCl, δ: 8.78 (s, IH, Ar), 8.51 (m, IH, Ar), 7.08-7.92 (m, 5H, Ar), 2.51 (t, 2H, CΑ), 1.20 (q, 3H, Me) Description 31 Phenyl N-[5-phenyI-3-(pyrid-3-yl)phenyl]carbamate The tide compound (0.289g, 100%) was prepared by mediodology of description 67 using 5-phenyl-3-(pyrid-3-yl) aniline (0:194mg, 0.79 mmol), phenyl chloroformate (0.12 ml, 0.87 mmol) and triethylamine (0.12ml, 0.81 mmol) in DCM (10 ml) H NMR 250 MHz CDC1, δ: 8.92 (br, IH, Ar), 8.65 (d, IH, Ar), 7.95 (d, IH, Ar), 7.82 (s, IH, Ar), 7.72-7.12 (m, 8H, Ar) Description 32 3-(3-Nitrobenzoylamino)-pyridine A solution of 3-aminopyridine (2 g, 20 mmol) in tetrahydrofuran (100 ml) was treated at 0° C widi triethylamine (3 ml, 2.2 g, 22 mmol) and dien a solution of 3- nitrobenzoyl chloride (3.7g, 20 mmol) in tetrahydrofuran (50 ml). After 0.5 h the reaction mixture was diluted widi water (400 ml) and set aside in the fridge for 3 days. Filtration and drying afforded d e tide compound as a purple crystalline solid (4.82 g, 99%). iH NMR (D6-DMSO) 7.40 (IH, m), 7.85 (IH, t, J 8 Hz), 8.20 (IH, d, J 8 Hz), 8.30- 8.50 (3H, m), 8.80 (IH, s), 8.95 (IH, d, J 2 Hz). Description 33 3-(3-Aminobenzoyiamino)-pyridine A solution of 3-(3-nitrobenzoylamino)-pyridine (2g, 8.23 mmol) in ethanol (200 ml) was treated widi 10% palladium on charcoal (0.5 g) and hydrogenated at atmospheric pressure for 4 h. Filtration and evaporation afforded d e product as a white solid (1.51g, 86%) !H NMR (D6-DMSO) 5.40 (2H, bs), 6.75 (IH, d, J 8 Hz), 7.0-7.2 (3H, m), 7.40 (IH, m), 8.15 (IH, d, J 8 Hz), 8.30 (IH, m), 8.90 (IH, d, J 2 Hz). Description 34 5-Methylthio-6-trifluoromethy 1-1- (3-ethoxycarbonyl phenyl carbamoyl)indoline To a stirred solution of carbonyl diimidazole (1.782g, 11 mmol) in dichloromethane (20 ml) was added dropwise a solution of ediyl 3-amino benzoate (1.65g, 10 mml) in dichloromediane (20 ml). After 1 hour the reaction mixture was evaporated under reduced pressure before being treated widi 5 -methylthio-6- trifluoromethyl indoline (2.33g, 10 mmol) and dimethylformamide (30 ml) and heated to 100° C. After 1 hour the reaction mixture was cooled and water added forming a yellow precipitate. This was filtered and dried to give die product as a yellow solid (4.19g, 99%), m.p. 195-7° C. !H NMR (DMSO) δ: 8.85 (IH, s); 8.2 (2H, d, J6Hz); 7.9 (IH, d, J7Hz); 7.6 (IH, d, J7Hz); 7.4 (2H, t, J6Hz); 4.3 (2H, q, J7Hz); 4.2 (2H, t, J8Hz); 3.25 (2H, t, J8Hz); 2.5 (3H, s); 1.3 (3H, t, J7Hz). Description 35 5-Methylthio-6-trifluoromethyl-l-(4-ethoxycarbonyl phenyl carbamoyl) indoline This was made in die same manner as Description 34 using ethyl-4-amino benzoate to give the product as a yellow solid (3.948g, 93%), m.p. > 200° C. J H NMR (DMSO) δ: 8.95 (IH, s); 8.2 (IH, s); 7.9 (2H, d, J7Hz); 7.75 (2H, d, J7Hz); 7.4 (IH, s), 4.2 (4H, m); 3.25 (2H, t, J8Hz); 2.5 (3H, s); 1.3 (3H, t, J7Hz) Description 36 5-Methylthio-6-trifluoromethyl-l-(3-carboxy phenyl carbamoyl)indoline To a suspension of 5-methylthio-6-trifluoromethyl-l-(3-ethoxy carbonyl phenyl carbamoyl) indoline (3g, 7.1 mmol) in ethanol (30 ml) was added aqueous sodium hydroxide solution (5M) (7.1 ml, 35.5 mmol) and heated gently for 2 hours. It was then allowed to cool and acidified widi aqueous hydrochloric acid (5M) forming a white precipitate which was filtered and dried to yield die product as a white solid (2.324g, 83%), mp >200° C. l H NMR (DMSO) δ: 12.95 (IH, s); 8.85 (IH, s); 8.2 (2H, s); 7.85 (IH, d, J7Hz); 7.6 (IH, d, J7Hz); 7.4 (2H, t, J7Hz); 4.2 (2H, t, J6Hz); 3.25 (2H, t, J6Hz); 2.5 (3H, s) Description 37 5-Methylthio-6-trifluoromethyl-l-(4-carboxy phenyl carbamoyl) indoline This was made in die same manner as Description 36 using 5-methyldιio-6- trifluoromethyl- l-(4-ethoxycarbonyl phenyl carbamoyl) indoline to give die product as a pale green solid (2.455g, 88%), mp >200° C. Ϊ H NMR (DMSO) δ: 1.27 (IH, s); 8.9 (IH, s); 8.2 (IH, s); 7.9 (2H, d, J7Hz); 7.7 (2H, d, J7Hz); 7.4 (IH, s); 4.2 (2H, t, J8Hz); 3.75 (2H, t, J8Hz); 2.5 (3H, s) Description 38 3- (Py rid-3-y laminosul phonyl)-nitrobenzene To a stirred solution of 3-aminopyridine (2g, 21.3 mmol) in pyridine (100 ml) was added 3-nitrobenzene sulphonyl chloride (4.43g, 20 mmol) and die mixture was heated to 50° C for 3 hours. After cooling it was partitioned between ethyl acetate and water and the organic washed with water (x2) and half saturated aqueous sodium chloride solution, separated, dried and evaporated to give a crude yield of 4.96g. It was then triturated with dichloromediane and sonicated for 0.25 hours before being filtered and dried to give the product as a pink solid (4.279g, 72%) iH NMR (DMSO) δ: 10.9 (IH, s); 8.45 (2H, d, J7Hz); 8.3 (2H, s); 8.15 (IH, d, J7Hz); 7.9 (IH, t, J7Hz); 7.55 (IH, d, J7Hz); 7.3 (IH, q, J5Hz). Description 39 3-(Pyrid-3-ylaminosulphonyl)-aminobenzene To a solution of 3-(pyrid-3-ylaminosulphonyl)-nitrobenzene (4.279g, 15.3 mmol) in ethanol (500 ml)/dimethylformamide (50 ml) was added 10% palladium catalyst on charcoal (lg) and die reaction mixture was hydrogenated at atmospheric pressure for 2 hours. The reaction mixture was then filtered through kieselguhr before being evaporated under reduced pressure to give the product as a white solid (3.749g, 98%) !H NMR (DMSO) δ: 10.4 (IH, s); 8.25 (IH, s); 8.2 (IH, d, J5Hz); 7.5 (IH, d, J7Hz); 7.3 (IH, q, 5Hz); 7.15 (IH, t, J7Hz); 6.95 (IH, s); 6.8 (IH, d, J7Hz); 6.7 (IH, d, J7Hz); 5.6 (2H, s) Description 40 3-(3-Nitrobenzoyl)pyridine The tide compound (1.55g, 25%) was prepared using die metiiod of Langhals et al (Liebigs Ann. Chem. 1982, 930-949), and purified by flash column chromatography on silica gel, eluting with 30% etiiyl acetate 60-80° petroleum ether *H NMR (200 MHz, CDCI3) δ: 7.40-7.60 (IH, m); 7.75 (IH, t), 7.98-8.23 (2H, m), 8.50 (IH, dd), 8.59-8.70 (IH, m), 8.90 (IH, dd), 9.01 (IH, d) Description 41 3-(3-Aminobenzoyl)pyridine 3-(3-Nitrobenzoyl)pyridine (1.55g, 0.006 mole) was suspended in etiianol (35 ml) and treated portionwise widi a solution of tin (II) chloride (4.56, 0.024 mmole) in cone. HCl (7 ml). The reaction mixture was stirred at 50° C for 2 hours. After allowing to cool to room temperature, water (50 ml) was added and die mixture basified with 10% aqueous sodium hydroxide, extracted into etiiyl acetate, dried (Na2SO4) and evaporated in vacuo to afford die title compound (1.14g, 85%) as a pale oil *H NMR (200 MHz; CDCI3) δ: 3.90 (2H, s), 6.81-7.03 (IH, m), 7.03-7.20 (2H, m), 7.28 (IH, t), 7.39-7.59 (IH, m), 8.14 (IH, dd), 8.80 (IH, dd), 9.01 (IH, s) Description 42 Trans-4-[2-ethenyl-(4-pyridyl)]-nitrobenzene (D42) A solution of (4-nitrobenzyl)triphenylphosphonium bromide (32g, 66 mmol in ethanol (100 ml) was treated widi sodium med oxide (3.6g, 66 mmol). After 0.75 h pyridine-4-carboxaldehyde (5.04 ml, 52.8 mmol) was added and die mixture stirred for 16 h. The mixture was subjected to an ethyl acetate/dilute brine workup. Drying, evaporation and chromatography afforded die product as an equal mixture of isomers. Recrystallisation from ethyl acetate petroleum ether afforded die title compound (single isomer) as a yellow solid (2.72g, 17%). !H NMR (D6-DMSO) 7.50 (IH, d), 7.65 (2H, d), 7.70 (IH, d), 7.95 (2H, d), 8.30 (2H, d), 8.65 (2H, d). Description 43 Trans-4-[2-ethenyl-(4-pyridyl)]-aniline (D43) A suspension of trans-4-[2-ethenyl-(4-pyridyl)]-nitrobenzene (D42) (0.5g, 2.2 mmol) in ethanol (30 ml) at 50°C was treated witii a solution of stannous (II) chloride (1.25g, 6.6 mmol) in concentrated hydrochloric acid (2 ml). The mixture was maintained at 50°C overnight tiien evaporated to dryness. The residue was partitioned between ethyl acetate and 5M aqueous sodium hydroxide solution. Drying and evaporation afforded a yellow solid which was triturated widi etiier- petroleum ether (1:1) affording the title compound as a yellow solid (100 mg. 23%). ^ NMR (D6-DMSO) 5.50 (2H, bs), 6.60 (2H, d), 6.85 (IH, d), 7.30-7.50 (5H, m), 8.45 (2H, d) Description 44 4-Nitro-2-(pyridin-3-yloxy)pyridine-N-oxide (D44) Sodium hydride (0.27g of an 80% dispersion in oil, 9 mmol) was added to a solution of 3-hydroxypyridine (0.854g, 9 mmol) in THF (3 ml) at 0°C. The mixture was then stirred for 1 h at room temperature before 2-chloro-4-nitropyridine-N-oxide* (2g, 9 mmol) was added. The resulting solution was heated at reflux for 16h, cooled, poured into water (100 ml) and extracted widi dichloromediane (3 x 100 ml). The combined extracts were dried (Na^SO,) and evaporated. The residue was chromatographed on silica using ethyl acetate as eluant to afford the title compound (1.74g, 83%) as a solid. iH NMR (250 MHz; CDC1,) δ: 7.42 (2H, m), 7.83 (IH, m), 8.00 (IH, dd, J=8Hz, 2Hz), 8.42 (IH, d, J 8Hz), 8.51 (IH, m), 8.59 (IH, m). * G.C. Finger and L.D. Starr, J. Am. Chem. Soc, 81, 2674 (1959) Description 45 4-Amino-2-(pyridin-3-yIoxy)pyridine (D45) 4-Nitro-2-(pvridin-3-yloxy)pyridine-N-oxide (D44) (lg, 4.3 mmol) in acetic acid (75 ml) was treated widi iron powder (1.2g, 21.4 mmol) at room temperature. After 2 h the mixture was concentrated under reduced pressure and partitioned between 2M aq NaOH (100 ml) and dichloromethane (4 x 100 ml). The combined extracts were dried and evaporated to a white crystalline solid (0.75g, 93%) which was used widiout further purification. l ~~ NMR (250 MHz; CDC1,) δ: 4.25 (2H, br), 6.17 (IH, d, J 2Hz), 6.33 (IH, dd, J 7Hz, 2Hz), 7.26 (IH, s), 7.32 (IH, dd, J 8Hz, 5Hz), 7.48 (IH, m, J 8Hz), 7.82 (IH, d, J 7Hz), 8.42 (IH, m, J 5Hz), 8.48 (IH, d, J 2Hz). Description 46 5-Nitro-l-(3-pyridylmethyI)indole (D46) 5-Nitroindole (0.49, 3 mmol) was treated widi sodium hydride (0.198g, 6.6 mmol) in dry dimetiiylformamide (20 ml). After 15 min at room temperature, 3-picolyl chloride hydrochloride (0.49g, 3 mmol) was added and die mixture was stirred at room temperature for 24 h, then poured into water. The precipitate was filtered off, washed witii water and dried to give the title compound (0.67g, 88%), m.p. 131-4°C. iH NMR (CDCy δ: 5.40 (2H, s), 6.75 (IH, d, J=3), 7.2-7.4 (4H, m), 8.09 (IH, dd, J=8,2), 8.52 (IH, s), 8.57 (IH, d, J=4), 8.61 (IH, d, J=2). Description 47 5-Nitro-l-(4-pyridylmethyI)indole (D47) The title compound was prepared by die method of Description 46 using 4-picolyl chloride hydrochloride. Yield 87%, m.p. 134-136°C iH NMR (CDCl,) δ: 5.41 (2H, s), 6.80 (IH, d, J=3), 6.93 (2H, d, J=7), 7.23 (IH, d, J=8), 7.30 (IH, d, J=3), 8.10 (IH, dd, J=8,2), 8.57 (2H, d, J=7), 8.64 (IH, d, J=2) Description 48 5-Amino-l-(3-pyridylmethyl)indole (D48) To a stirred suspension of nitroindole (D46) (0.63g, 2.5 mmol), and iron powder (0.4 lg, 7.2 mmol) in methanol (20 ml) was added a solution of ammonium chloride (0.66g, 12.4 mmol) in water (13 ml). The mixture was then heated under reflux for 12 h, then filtered while hot and evaporated. The residue was diluted widi water and extracted with dichloromethane. The organic extract was washed widi brine, dried and evaporated to give die title compound (0.40g, 72%) as a gum. ^ NMR (CDCy δ: 5.25 (2H, s), 6.38 (IH, d, J=3), 6.63 (IH, dd, J=8,2), 6.94 (IH, d, J=2), 7.03 (IH, d, J=8), 7.05 (IH, d, J=3), 7.18 (IH, dd, J=7,4), 7.29 (IH, d, J=7), 8.52 (2H, broad s). MS(API) m z=224(MH * ) Description 49 5- Amino- l-(4-pyridylmethyl)indole (D49) The tide compound was prepared by the method of Description 48, from nitroindole D47. Yield 87%. iH NMR (CDC1,) δ: 3.52 (2H, broad), 5.27 (2H, s), 6.41 (IH, d, J=3), 6.63 (IH, dd, J=8,2), 6.90-7.0 (4H, m), 7.05 (IH, d, J=3), 8.50 (2H, d, J=7). MS(API) m/z=224(MH * ) Description 50 5-Nitro-l-(3-pyridyl)indole (D50) A mixture of 5-nitroindole (0.49g, 3 mmol), 3-bromopyridine (0.95g, 6 mmol), copper (I) bromide (60 mg, 0.42 mmol) and potassium carbonate (0.62g, 4.5 mmol) in pyridine (2 mL) and nitrobenzene (0.6 mL) was heated under reflux for 4 h. After cooling, the mixture was diluted widi water and extracted widi etiiyl acetate. The organic extract was washed widi water, dried and evaporated. The residue was chromatographed on silica gel eluted widi ethyl acetate to give the title compound (0.62g, 86.5%), mp. 164-5°C. iH NMR (CDC δ: 6.93 (IH, d, J=3), 7.49 (IH, d, J=3), 7.51 (IH, d, J=8), 7.57 (IH, dd, J=7,5), 7.87 (IH, dm, J=7), 8.18 (IH, dd, J=8, 2), 8.72 (IH, d, J=5), 8.85 (lH, d, J=2) Description 51 5-Nitro-l-(4-pyridyl)indole (D51) The tide compound was prepared by die metiiod of Description 50, using 4- bromopyridine. Yield 0.42g (59%) iH NMR (CDCl,) δ: 7.09 (IH, d, J=3), 7.79 (2H, d, J=6), 7.94 (IH, d, J=8), 8.09 (IH, d, J=3), 8.13 (IH, dd, J=8,2), 8.69 (IH, d, J=2), 8.80 (2H, broad) MS(API) m/z=240(MH * ) Description 52 5-Amino-l-(3-pyridyl)indole (D52) The tide compound was prepared by die metiiod of Description 48, from nitroindole (D50). Crude product was chromatographed on silica gel eluted widi etiiyl acetate to give the tide compound (0.34g, 63%) as a gum. H NMR (CDCI 3 ) δ: 3.59 (2H, broad), 6.55 (IH, d, J=3), 6.71 (IH, dd, J=8,2), 6.98 (IH, d, J=2), 7.25 (IH, d, J=3), 7.37 (IH, d, J=8), 7.64 (IH, dd, J=7,5), 7.82 (IH, dm, J=7), 8.58 (IH, d, J=5), 8.81 (IH, d, J=2) MS(API) m/z=210(MIf ) Description 53 5-Amino-l-(4-pyridyI)indole (D53) A mixture of nitroindole (D51, 0.41g, 1.8 mmol), tin (II) chloride (1.7 g, 8.8 mmol), and concentrated hydrochloric acid (2 ml) in ethanol (10 ml) was heated under reflux for 70 min. The mixture was evaporated and the residue was dissolved in water, basified with dilute sodium hydroxide and extracted widi dichloromediane. The extract was dried and evaporated to give the tide compound (0.36g, 96%). iH NMR (CDCl,) δ: 3.62 (2H, broad), 6.56 (IH, d, J=3), 6.72 (IH, dd, J=8,2), 6.95 (IH, d, J=2), 7.32 (IH, d, J=3), 7.41 (2H, d, J=6), 7.54 (IH, d, J=8), 8.68 (2H, d, J=6) MS(API) m/z=210(MH * ) Description 54 5-Methylthio-6-trifluoromethyl-l-(3-ethoxycarbonylphenyl carbamoyl)-indoline (D54) This was prepared in 74% yield by urea formation between ethyl 3-aminobenzoate and 5-medιylthio-6-trifluoromethyl indoline, (D7) using carbonyl diimidazole as the coupling agent. Description 55 5-Meth ythio-6-trifluoromethy l-l-(3-carboxyphenylcarbamoyI)-indoline (D55) This was prepared in 86% by basic hydrolysis of die corresponding ester D54. iH NMR (CDCl,) δ: 2.50 (3H, s), 3.30 (2H, t), 4.20 (2H, t), 7.40-7.50 (2H, m), 7.60 (IH, m), 7.85 (IH, d), 8.25 (2H, m), 8.80 (IH, s) Description 56 4-(3-NitrophenyI)-2-(3-pyridyI)-thiazoIe, hydrobromide salt A mixture of 2-bromo-3'-nitroacetophenone (5g, 20 mmol) and tiiionicotinamide (2.76g, 20 mmol) in ethanol (25 ml) was heated to reflux for 1 h, during which time extensive precipitation occurred. Filtration and drying afforded die product as a yellow solid (6.7g, 92%). iH NMR δ (DMSO) 7.80 (IH, t), 7.95 (IH, m), 8.25 (IH, dd), 8.55 (IH, d), 8.70 (IH, s), 8.90 (3H, m), 9.45 (IH, d) Description 57 4-(3-AminophenyI)-2-(3-pyridyl)-thiazole A suspension of 4-(3-nitrophenyl)-2-(3-pyridyl)-dιiazole hydrobromide (3.6g, 10 mmol) in ethanol (150 ml) was treated with a solution of tin (II) chloride (3.7g, 30 mmol) in concentrated hydrochloric acid (12 ml). The mixture was heated at 50°C for 16 h. A further portion of tin (TI) chloride (2.9 g, 15 mmol) was added and die mixture heated at 50°C for a further 4 hours before being evaporated to dryness. The residue was partitioned between ethyl acetate and 1M aqueous sodium hydroxide. The ethyl acetate extract was dried (Na 7 SO 4 ) and filtered tiirough a plug of silica. Evaporation afforded the title compound as a yellow solid (2.15g, 85%). iH NMR (CDCy δ: 3.80 (2H, bs), 6.70 (IH, dd), 7.20 (2H, m), 7.40 (2H, m), 7.50 (IH, s), 8.30 (IH, dt), 8.65 (IH, dd), 9.25 (IH, d). Description 58 4-(4-NitrophenyI)-2-(4-pyridyI)-thiazole This was prepared in die same manner as 4-(3-nitrophenyl)-2-(3-pyridyl)-dιiazole, hydrobromide salt and liberated to die free base form with 5M NaOH to give die product as a brown solid (4g,69%). Η NMR (CDCl,) δ: 8.8 (2H, d), 8.35 (2H, d), 8.15 (2H, d), 7.9 (2H, d), 7.8 (IH, s). Description 59 4-Fluoro-3-(pyrid-3-yl)phenylcarbonyl azide (D59) 3-Bromo-4-fluorobenzotrifluσride was coupled widi 3-pyridylboronic acid using Suzuki methodology. Hydrolysis of the product using cone, sulphuric acid and chlorosulphonic acid followed by esterification in methanol and cone, sulphuric acid gave mediyl 4-fluoro-3-(pyrid-3-yl)benzoate. Treatment with hydrazine hydrate afforded the hydrazide which was diazotised widi sodium nitrite and basified widi potassium carbonate to give die title compound. Η NMR 250 MHz δ: 8.82 (br, IH), 8.67 (br, IH), 8.17 (dd, IH), 8.09 (m, IH), 7.90 (dd, IH), 7.42 (m, IH), 7.30 (m, IH). Description 60 3-Fluoro-5-(pyrimidin-5-yl)phenylcarbonyl azide (D60) 3-Bromo-5-fluorobenzotrifluoride was lithiated with n-butyllithium and treated with tri-isopropylborate to give 3-fluoro-5-trifluoromethylphenyl boronic acid. This was coupled to 5-bromopyrimidine, using Suzuki methodology to afford 3-fluoro-5- (pyrimidin-5-yl)benzotrifluoride. Hydrolysis widi cone, sulphuric acid and chlorosulphonic acid afforded 3-fluoro-5-(pyrimidin-5-yl)benzoic acid. This was converted to die methyl ester by treatment with medianol and cone, sulphuric acid, and to die hydrazide by treatment with hydrazine hydrate. Diazotisation and treatment with potassium carbonate afforded die title compound. Η NMR (200 MHz, CDCl,) δ (ppm): 7.57 (IH, dt J=l, 8), 7.83 (IH, m), 8.06 (IH, t, J=l), 8.99 (2H, s), 9.29 (IH, s) Description 61 4-Chloro-3-(4-methyl-3-pyridyl)nitrobenzene (D61) The tide compound was prepared by a Suzuki coupling of 3-bromo-4- chloronitrobenzene and 4-metiιyl-3-pyridylboronic acid. This gave (D61) (0.2g, 33%). Description 62 4-Chloro-3-(4-methyl-3-pyridyl)aniline (D62) The title compound was prepared by stannous chloride reduction of die nitro compound (D61). This gave (D62) (0.105g, 95%). Description 63 2,3-Dihydro-5-nitro-7-(pyrid-3-yl)benzofuran (D63) 2,3-Dihydro-7-iodo-5-nitrobenzofuran (0.76g, 0.0026 mole) and 3-pyridylboronic acid (0.32g, 0.0026 mole) in 50% aqueous 1,2-dimethoxyethane (50 ml) were treated under argon with sodium carbonate (1.17g, 0.011 mole) and tetrakis triphenylphosphine palladium (0) (0.06g, 0.000052 mole) and heated under reflux for 18 hours. The mixture was allowed to cool to ambient temperature, diluted widi deionised water, extracted into etiiyl acetate, dried (Na^O and evaporated in vacuo. The residue was purified by flash column chromatography on silica gel, eluting with 30% ethyl acetate/60-80° petroleum etiier to afford the title compound (0.19g, 30%) as a yellow solid. NMR (200 MHz, CDCl,) δ (ppm): 3.40 (2H, t, J=9), 4.83 (2H, t, J=9), 7.40 (IH, q, J=3, 5), 8.02 (IH, dt, J=l,9), 8.12 (IH, m), 8.30 (IH, d, J=3), 8.62 (IH, dd, J=l, 5), 8.98 (lH, d, J=l). Description 64 5-Amino-2,3-dihydro-7-(pyrid-3-yl)benzofuran (D64) 2,3-Dihydro-5-nitro-7-(pyrid-3-yl)benzofuran (D63) (0.19g, 0.00079 mole) in ethanol (20 ml) was treated widi a solution of tin II chloride (0.75g, 0.0040 mole) in cone. hydrochloric acid (1 ml) and heated at 50°C for 2 hours. A further 0.38g tin II chloride in cone, hydrochloric acid (0.5 ml) was added and the mixture was heated at 50°C for Vi hour and stirred at ambient temperature for 18 hours. Deionised water (5 ml) was added and the mixture was basified witii 10% sodium hydroxide solution, extracted into etiiyl acetate, dried (Na j SO 4 ) and evaporated in vacuo to afford die titie compound (0.13g, 82%) as a dark oil. NMR (200 MHz, CDCl,) δ (ppm): 3.20 (2H, t, J=9), 3.43-3.70 (2H, br s), 4.57 (2H, t, J=9), 6.63 (2H, s), 7.32 (IH, m), 8.01 (IH, dt, J=l, 5), 8.51 (IH, dd, J=l, 5), 8.89 (IH, t, J=l). Description 65 Phenyl N-[2^-dihydro-7-(pyrid-3-yl)benzofιιran-5-yI]carbamate (D65) 5-Amino-2,3-dihydro-7-(pyrid-3-yl)benzofuran (D64) (0.13g, 0.00062 mole) was dissolved in dichloromediane (10 ml) and cooled to 0°C under argon. Triethylamine (0.09 ml, 0.00068 mole) was added, followed dropwise by phenyl chloroformate (0.08 ml, 0.00065 mole) and the mixture was stirred at ambient temperature for 2 hours. The reaction mixture was washed widi deionised water, dried (Na,SO 4 ) and evaporated in vacuo to afford die title compound (0.20g, 97%) as a cream solid. Η NMR (200 MHz, CDCl,) δ (ppm): 3.38 (2H, t, J=9), 4.64 (2H, t, J=9), 7.05-7.58 (9H, m), 8.06 (IH, dt, J=l, 5), 8.57 (IH, dd, J=l,5), 8.95 (IH, d, J=l). Description 66 Phenyl N-(3-Fluoro-5-(pyrid-3-yI)phenyI)carbamate (D66) 3-Fluoro-5-(pyrid-3-yl)aniline (1.05g, 0.0050 mole) in dry dichloromethane was treated under argon with triethylamine (1.12 ml, 0.0080 mole) followed dropwise by phenyl chloroformate (0.97 ml, 0.0077 mole) and stirred at ambient temperature for 18 hours. The reaction mixture was washed (x2) with deionised water, dried (Na j SO and evaporated in vacuo to afford die title compound (l.lg, 71%) as an off white solid. NMR (200 MHz; DTJMSO) δ: 7.20-7.49 (3H, m), 7.49-7.59 (5H, m), 7.63 (IH, d), 8.07 (IH, dt), 8.63 (IH, d), 8.87 (IH, s), 10.61 (IH, s) Description 67 Phenyl N-(4-Chloro-3-(pyrid-3-yl)phenyl)carbamate (D67) 4-Chloro-3-(pyrid-3-yl)aniline (0.08g, 0.00039 mole) in isopropyl alcohol (8 ml) was cooled to -40°C and treated under argon with triethylamine (0.06 ml, 0.00043 mole) followed dropwise by phenyl chloroformate (0.051 ml, 0.00041 mole). The reaction mixture was stirred at -40°C for half an hour and allowed to warm to ambient temperature. The solvent was removed in vacuo and the residue dissolved in dichloromethane, washed widi H j O, dried (Na,SO 4 ) and evaporated in vacuo to afford the title compound (0.12g, 95%) as an orange solid. Η NMR (200 MHz; CDCl,) δ: 7.05-7.56 (10H, m), 7.82 (IH, dt), 8.64 (IH, dd), 8.71 (lH, d) Description 68 Phenyl N-[(5-Methyl-l y 2,4-oxadiazoI-3-yl)phenyl]carbamate (D68) The tide compound (0.23g, 97%) was prepared using the method of D67. Η NMR (200 MHz, CDCl,) δ: 2.65 (3H, s), 7.08 (IH, s), 7.16-7.53 (6H, m), 7.66- 7.87 (2H, m), 8.06 (lH,t). Description 69 Phenyl N-[4-Methyl-3-(4-methylpyrid-3-yl)phenyl]carbamate (D69) The title compound was prepared as in the method of description 67 from the corresponding aniline. This gave (2.1g, 97%) of an oil. iH NMR (CDCl,) δ: 2.05 (3H, s), 2.15 (3H, s), 7.08-7.45 (10H, m), 8.30 (IH, s), 8.48 (IH, d, J=8Hz). Example 1 l-[(3-Pyridyl)-3-phenyl carbamoyl]-5-methoxy-6-trifluoromethyl indoline 3-(3-Pyridyl)aniline (0.27g, 1.6mmol) in dichloromethane (5ml) was added dropwise over 5 minutes to a solution of 1,1-carbonyldiimidazole (0.28g, 1.75mmol) in dichloromethane (5ml). After 2 hour the mixture was evaporated to dryness and die residue dissolved in N,N-dimethylformamide (20ml). 5-Methoxy-6- trifluoromethyl indoline (0.35g, l.όmmol) was added and the mixture heated to 100°C for lh. Water (30ml) was added and die mixture was set aside in die fridge for lh. Filtration and drying afforded a brown solid (0.59g). Chromatography on silica, eluting with a gradient of 0-3% methanol in dichloromethane afforded the title compound as a white solid (0.56g, 85%), mp 193-4<>C. iH NMR (D6 DMSO) 3.25 (2H, t), 3.85 (3H, s), 4.20 (2H, t) 7.20 (IH, s), 7.40 (2H, m), 7.50 (IH, m), 7.90 (IH, s), 8.05 (IH, dm), 8.15 (IH, s), 8.60 (IH, dm), 8.70 (IH, s), 8.85 (IH, s). The mesylate salt can be prepared by treatment with metiianesulphonic acid in acetone. The following examples were similarly prepared: Example 2 l-[(4-Pyridyl)-3-phenyl carbamoyl]-5-πιethy]thio-6-trifluoromethyl indoline Yield = 25% iH NMR (D°-DMSO) 2.52 (3H, s), 3.30 (2H, t), 4.25 (2H, t), 7.50 (3H, m), 7.70 (3H, m), 8.02 (IH, s), 8.25 (IH, s), 8.70 (2H, dd), 8.80 (IH, s). Example 3 l-[(3-Pyridyl)-3-phenyl carbamoyI]-5-methylthio-6-trifluoromethyl indoline. Yield = 42%, m.p. 208-210°C iH MNR (D^DMSO) 2.50 (3H, s), 3.30 (2H, t), 4.20 (2H, t), 7.40 (3H, m), 7.50 (IH, M), 7.65 (IH, m), 7.90 (IH, s), 8.10 (IH, dm), 8.20 (IH, s), 8.60 (IH, m), 8.80 (IH, s), 8.90 (lH, m). The mesylate salt can be prepared by treatment with methanesulphonic acid in acetone. Example 4 l-[(3-Pyridyl)-4-phenyl carbamoyl]-5-methoxy-6-trifluromethylindoIine. Yield = 85%, m.p. = >230°C iH NMR (D°-DMSO) 3.30 (2H, t), 3.85 (3H, s), 4.20 (2H, t), 7.20 (IH, s), 7.45 (IH, m), 7.70 (4H, m), 8.05 (IH, m), 8.15 (IH, s), 8.55 (IH, m), 8.70 (IH, s), 8.90 (IH, m) Example 5 l-[(4-Pyridyl)-4-phenyl carbamoyl]-5-methoxy-6-trifluoromethyl indoline Yield = 5%, m.p. = >210°C iH NMR (DO-DMSO) 3.30 (2H, t), 3.85 (3H, s), 4.20 (2H, t), 7.20 (IH, s), 7.70 (2H, d), 7.75 (4H, m), 8.15 (IH, s), 8.60 (2H, d), 8.85 (IH, s) Example 6 l-[(2-Pyridyl)-3-phenyl carbamoyI]-5-methoxy-6-trifluoromethyl indoline. Yield = 40%, m.p. = 220-225°C iH NMR (D 6 -DMSO) 3.30 (2H, t), 3.85 (3H, s), 4.20 (2H, t), 7.20 (IH, s), 7.40 (2H, m), 7.70 (2H, m), 7.90 (2H, m), 8.15 (IH, s), 8.35 (IH, s), 8.65 (IH, m), 8.70 (IH, s). Example 7 l-[4-Methyl-3-(3-Pyridyl)-phenylcarbamoyl]-5-methoxy-6-trifluoromethyl indoline Yield = 26%, m.p. = 211-212°C iH NMR (D°-DMSO) 2.2 (3H, s), 3.28 (2H, t), 3.85 (3H, s), 4.11 (2H, t), 6.44 (IH, s), 6.85 (IH, s), 7.18-7.45 (4H, m), 7.59-7.72 (IH, m), 8.22 (IH, s), 8.49-8.69 (2H, m). The mesylate salt can be prepared by treatment with med anesulphonic acid in acetone. Example 8 l-[3-Fluoro-5-(3-pyridyl)phenylcarbamoyI]-5-methoxy-6-trifluoromethyl indoline. Yield = 26%, m.p.= 220-223°C iH NMR (D6-DMSO) 3.29 (2H, t), 3.85 (3H, s), 4.21 (2H, t), 7.23 (IH, s), 7.30 (IH, t), 7.54 2H, m), 7.65 (IH, dt), 7.76 (IH, s), 8.09 (IH, dt), 8.15 (IH, s), 8.62 (IH, dd), 8.78-9.00 (2H, m). The mesylate salt can be prepared by treatment with medianesulphonic acid in acetone. m.p. 198 - 199°C. Example 9 l-[2-Fluoro-5-(3-pyridyl) phenyl carbamoyI]-5-methoxy-6-trifluoromethyI indoline. Yield = 10%, m.p. 233°C (decomp) iH NMR (D6-DMSO) 3.20 (2H, t), 3.82 (3H, s), 3.94 (2H, t), 7.13-7.28 (2H, m), 7.38-7.58 (3H, m), 7.87 (IH, dt), 7.98 (IH, S), 8.35 (IH, s), 8.55 (IH, dd), 8.64 (IH, d) Example 10 l-(5-Phenyl pyrid-3-yl carbamoyl)-5-methoxy-6-trifluoromethyl indoline A mixture of l-(5-bromo-pyrid-3-yl carbamoyl)-5-methoxy-6-trifluoromethyl- indoline (D14, 208mg, 0.5mmol), phenyl boronic acid (300mg, 2.4mmol), sodium carbonate (0.32g, 3mmol) and tetrakis (triphenylphosphine) palladium (0) (30mg) in dimethoxyetiiane- water (5ml- lml) was heated to reflux under argon for lOh. The cooled reaction mixture was partitioned between ethyl acetate-half saturated brine. The organic extract was dried and evaporated affording a brown solid (0.14g). Chromatography on silica, eluting with a gradient of 0-5% methanol in ethyl acetate afforded the titie compound as a white crystalline solid (lOOmg, 48%), m.p. 162- 164°C. iH NMR (D^-DMSO) 3.30 (2H, t) 3.85 (3H, s), 4.20 (3H, t), 7.20 (IH, s), 7.50 (3H, m), 7.70 (2H, m), 8.10 IH, s), 8.30 (IH, m), 8.55 (IH, m), 8.75 (IH, m), 8.85 (IH, s). The mesylate salt can be prepared by treatment with methanesulphonic acid in acetone. The following examples were similarly prepared: Example 11 l-(5-Phenyl pyrid -3-yl carbamoyl)-5-methylthio-6-trifluoromethyl indoline Yield = 73%, m.p. = 208-214°C iH NMR (D6-DMSO) 2.50 (2H, s), 3.30 (2H, t), 4.20 (2H, t), 7.50 (4H, m), 7.70 (2H, m), 8.20 (IH, s), 8.30 (IH, m), 8.60 (IH, m), 8.75 (IH, m), 8.95 (IH, s). Example 12 l-[5-(3-PyridyI)-pyrid-3-yl carbamoyI]-5-methoxy-6-trifluoromethyI indoline. Yield = 29%, m.p. = 113-114 © C iH NMR (D°-DMSO) 3.30 (2H, t), 3.85 (3H, s), 4.20 (2H, t), 7.20 (IH, s), 7.55 (IH, m), 8.10 (IH, m), 8.15 (IH, s), 8.30 (IH, m), 8.60 (IH, ), 8.65 (IH, dd), 8.80 (IH, d), 8.95 (2H, m) The mesylate salt can be prepared by treatment with medianesulphonic acid in acetone. Example 13 l-[5-(4-TrifluoromethylphenyI)-pyrid-3-yl carbamoyl]-5-methoxy-6- trifluoromethyl indoline Yield = 48%, m.p. = 199-202<>C iH NMR (D6-DMSO) 3.30 (2H, t), 3.85 (3H, s), 4.20 (2H, t), 7.20 (IH, s), 7.89 (4H, m), 8.10 (IH, s), 8.35 (IH, m), 8.60 (IH, d), 8.80 (IH, d), 8.95 (IH, s). Example 14 l-[5-(4-Methylphenyl)-pyrid-3yl carbamoyl]-5-methoxy-6-trifluoromethyl indoline. Yield = 57%, m.p. = 190-191°C iH NMR (D-S-DMSO) 2.35 (3H, s), 3.30 (2H, t), 3.85 (3H s), 4.20 (2H, t), 7.20 (IH, s, 7.30 (2H, d), 7.60 (2H,d), 8.15 (IH, s), 8.25 (IH, m), 8.55 (IH, d), 8.75 (IH, d), 8.85 (IH, s). Example 15 l-[5-(2-Thienyl)-pyrid-3-yl carbamoyl]-5-methoxy-6-trifluoromethyl indoline Yield = 53%, m.p. = 193-208°C iH NMR (D^-DMSO) 3.30 (2H, t), 3.85 (3H, s), 4.20 (2H, t), 7.20 (2H, m), 7.65 (2H, m), 8.10 (IH, s), 8.25 (IH, t), 8.60 (IH, d), 8.75 (IH, d), 8.90 (IH, s). The mesylate salt can be prepared by treatment with medianesulphonic acid in acetone. Example 16 l-[5-(3-Thienyl)-pyrid-3-yl carbamoyI]-5-methoxy-6-trifluoromethyl indoline Yield = 30%, m.p. = 165-167<>C iH NMR (D^-DMSO) 3.30 (2H, t), 3.85 (3H, s), 4.20 (2H, t), 7.20 (IH, s), 7.60 (IH, dd), 7.75 (IH, m), 8.0 (IH, m), 8.15 (IH, s, 8.30 (IH, t), 8.65 (IH, d), 8.70 (IH, d), 8.90 (IH, s Example 17 l-[5-(2-Pyrrolyl)-pyrid-3-yl carbamoyl)-5-methoxy-6-trifluoromethyl indoline. Yield = 20%, m.p. = 218-219°C iH NMR (D-S-D SO) 3.30 (2H, t), 3.85 (3H, s), 4.20 (2H, t), 6.20 (IH, m), 6.55 (IH, m), 6.90 (IH, m), 7.20 (IH, s), 8.15 (2H, m), 8.50 (IH, d), 8.60 (IH, d), 8.80 OH, s). Example 18 l-[5-(4-Pyridyl)-pyrid-3-yl carbamoyl]-5-methoxy-6-trifluoromethyl indoline Yield = 71%, m.pt 230-234°C. iH NMR (D6_ D MSO) 3.30 (2H, t), 3.85 (3H, s), 4.20 (2H, t), 7.20 (IH, s), 7.75 (2H, m) 8.15 (IH, s), 8.40 (IH, t), 8.65 (IH, d), 8.70 (2H, m), 8.85 (IH, d). Example 19 l-[2-(3-Pyridyl)-thiazol-4-yl carbamoyl]-5-methoxy-6-trifluoromethyl indoline. A solution of acyl azide (D15) (370mg, l.ommol) in toluene (5ml) was heated to reflux for 0.25h. After cooling to room temperature, the solution of the isocyanate was added to a solution of 5-methoxy-6-trifluoromethyl indoline (0.35g, 1.6mmol) in dichloromethane (10ml). Filtration and drying afforded die titie compound as a white solid (lOOmg, 15%), m.p. >200°C. iH NMR 3.30 (2H, t), 3.85 (3H, s), 4.20 (2H, t), 7.20 (IH, s), 7.45 (IH, m), 7.55 (IH, s), 8.15 (IH, s, 8.30 (IH, dt), 8.65 (IH, dd), 9.15 (IH, m), 9.85 (IH, s). Example 20 l-[2-(2-PyridyI)-thien-5-yl carbamoyl]-5-methoxy-6-trifluoromethyl indoline. This was prepared from the corresponding acyl azide (D16) using the same procedure as for Example 19, affording the title compound as a pale yellow solid (0.45g, 73%), m.p. 205-215°C. J H NMR (D^-DMSO) 3.30 (2H, t), 3.85 (3H, s, 4.20 (2H, t), 6.80 (IH, d), 7.15 (IH, m), 7.25 (IH, s),7.50 (IH, d), 7.75 (2H, m), 8.20 (IH, S), 8.45 (IH, m), 9.95 (IH, s). Example 21 l-(3-Fluoro-5-(4-methyl-3-pyridyl)phenylcarbamoyI)-5-methoxy-6- trifluoromethylindoline A mixture of l-(3-fluoro-5-iodophenylcarbamoyl)-5-methoxy-6- trifluoromethylindoline (Oil, 0.31g, 0.65 mmol), 4-methyl-3-pyridylboronic acid (88 mg, 0.65 mmol), tetrakis (triphenylphosphine) palladium (O) (23 mg, 0.02 mmol) and sodium carbonate (0.3 lg, 3.0 mmol) in 1,2-dimethoxyethane (20 mL) and water (2 mL) was heated under reflux for 24 h, then cooled and poured into water. The aqueous mixture was extracted widi dichloromethane methanol, and die organic extract was washed widi brine, dried and evaporated. The residue was chromatographed on silica gel eluted widi 2-3% metiianol/dichloromethane to give the titie compound, which was recrystallised from dichloromethane/petrol (80 mg, 28%), Mp 191-5°C. iH NMR (d^MSO) δ: 2.31 (3H, s), 3.28 (2H, t, J=8), 3.85 (3H, s), 4.19 (2H, t, J=8), 6.94 (IH, d, J=8), 7.22 (IH, s), 7.37 (IH, d, J=6), 7.42 (IH, s), 7.61 (IH, d, J=12), 8.12 (IH, s), 8.40 (IH, s), 8.46 (IH, d, J=6), 8.82 (IH, s) MS (API): Found m/z=446 (MH * ), C B H If N,O l F 4 requires M+ 1=446 Example 22 l-(5-(2,6-Difluorophenyl)-3-pyridylcarbamoyl)-5-methoxy-6- trifluoromethylindoline A solution of 5-(2,6-difluorophenyl)nicotinoyl azide (D20, 0.46g, 1.8 mmol) in toluene (10 mL) was heated under reflux for 2h. After cooling, a solution of 5- methoxy-6-trifluoromethylindoline (Dll, 0.40g, 1.8 mmol) in dichloromethane (10 mL) was added and the mixture was stirred overnight at room temperature. The precipitate was filtered off and washed with petrol. The crude product was recrystallised from dichloromethane/petrol to give the title compound (0.66g, 82%), Mp. 217-9°C. iH NMR (d MSO) δ: 3.29 (2H, t, J=8), 3.84 (3H, s), 4.21 (2H, t, J=8), 7.22 (IH, s), 7.29 (2H, t, J=7), 7.56 (IH, quintet, J=7), 8.11 (IH, s), 8.15 (IH, s), 8.32 (IH, s), 8.80 (IH, s), 9.93 (IH, s). MS (API): m/z=450 (MIT), C^N^ j F, requires M+l = 450 Found: C, 54.84; H, 3.69; N, 8.64% C JH^O^ requires C, 58.80: H, 3.59; N, 9.35% Example 23 6-Chloro-5-methyl-l-(4-methyl-3-(pyrid-3-yl)-phenylcarbamoyl) indoline 4-Methyl-3-(pyrid-3-yl) aniline (0.30g, 0.0016 mole) in dry dichloromethane (20 ml) was added, under argon, to l,l'-carbonyldiimidazole in dry dichloromethane (10 ml) (0.30g, 0.0018 mole) and stirred at ambient temperature for 1 hour. The solvent was removed in vacuo and the residue dissolved in dry dimethylformamide (30 ml). 6- Chloro-5-methylindoline (see WO 95/01976) (0.27g, 0.0016 mole) in dry dimethylformamide (10 ml) was added and die mixture heated to 100°C for 1 hour. After cooling to ambient temperature, the solvent was removed in vacuo and die residue diluted widi deionised water (15 ml), extracted into dichloromethane (2 x 20 ml), dried (Na j SO 4 ) and evaporated in vacuo. The residue was purified by flash column chromatography on silica gel, eluting with 3% methanol/dichlσromethane and die resulting solid recrystallised from ethyl acetate/methanol/60-80° petroleum ether to afford the title compound (0.3 lg, 57%) as a cream solid (mp 202-203°C). Η NMR (270 MHz, d*DMSO) δ: 2.20 (3H, s), 2.24 (3H, s), 3.12 (2H, t, J=7), 4.13 (2H, t, J=7), 7.14 (IH, s), 7.25 (IH, d, J=7), 7.42-7.61 (3H, m), 7.81 (IH, dt, J=3, 7), 7.89 (IH, s), 8.49-8.69 (3H, m) MS (El) m/z = 377 (M + ) The mesylate salt can be prepared by treatment with medianesulphonic acid in acetone. Example 24 l-(4-Methyl-3-(pyrid-3-yl) phenylcarbamoyl)-5-thiomethyl-6-trifluoromethyl indoline 4-Methyl-3-(pyrid-3-yl) aniline (0.35g, 0.0019 mole) in dry dichloromediane (20 ml) was added, under argon, to l,r-carbonyldiimidazole (0.34g, 0.0021 mole) in dry dichloromediane (10 ml) and stirred at ambient temperature for 1 hour. The solvent was removed in vacuo and the residue dissolved in dry dimethylformamide (10 ml). 5-Thiomethyl-6-trifluoromethylindoline (D7) (0.44g, 0.0019 mole) in dry dimethylformamide (5 ml) was added and die mixture heated to 100°C for 2 hours. After cooling to ambient temperature, he solvent was removed in vacuo and die residue diluted widi deionised water (15 ml), extracted into dichloromethane (2 x 20 ml), dried (Na^SO and evaporated in vacuo. The residue purified by flash column chromatography on silica gel eluting with 3% methanol/ dichloromediane and die resulting solid was recrystallised from ethyl acetate/60-80 o petroleum ether to afford the title compound (0.1 lg, 13%) as a cream solid (mp 221-223°C) NMR (200 MHz; d*DMSO) δ: 2.20 (3H, s), 2.55 (3H, s), 3.38 (2H, t, J=8), 4.20 (2H, t, J=8), 7.26 (IH, d, J=9), 7.41-7.61 (4H, m), 7.81 (IH, dt, J=3,9), 8.20 (IH, s), 8.51-8.63 (2H, m), 8.69 (IH, s) MS (CI) m/z=444 (MIT) Example 25 l-(3-Fluoro-5-(pyrid-3-yl)phenylcarbamoyI)-5-thiomethyl-6-trifluoromethyI- indoline hydrochloride Phenyl N-(3-fluoro-5-(pyrid-3-yl)phenyl)carbamate (D66) (0.55g, 0.0018 mole) in dry dimediylformamide (30 ml) was treated, under argon, with 5-thiomethyl-6- trifluoromethyl indoline hydrochloride (D7) (0.49g, 0.0018 mole) and triethylamine (0.5 ml, 0.0036 mole) and heated to 100°C for 6 hours. After cooling to ambient temperature, the solvent was removed in vacuo. The residue was purified by flash column chromatography on silica gel, eluting with 3% methanol/dichloromethane and die resulting solid recrystallised from ethyl acetate/60-80 o petroleum ether to afford the title compound (0.39g, 49%) as an off white solid (mp 202-203°C) NMR (250 MHz, d*DMSO) δ: 2.52 (3H, s), 3.32 (2H, t, J=8), 4.22 (2H, t, J=8), 7.30 (IH, d, J=8), 7.45-7.58 (3H, m), 7.64 (IH, d, J=l 1), 7.78 (IH, s), 8.09 (IH, d, J=8), 8.23 (IH, s), 8.63 (IH, d, J=6), 8.87-9.01 (2H, m) MS (Electron Spray) m/z=448 (MH * ) Example 26 l-(4-Chloro-3-(pyrid-3-yl)phenylcarbamoyl)-5-methoxy-6- trifluoromethylindoline Phenyl N-(4-Chloro-3-(pyrid-3-yl)phenyl)caτbamate (D67) (0.12g, 0.00037 mole) in dry dimethylformamide (6 ml) was treated under argon, witii 5-methoxy-6- trifluoromethylindoline (Dll) (0.08g, 0.00037 mole) and heated to 120°C for 2 hours. After cooling to ambient temperature, the solvent was removed in vacuo. The residue was partitioned between IN aqueous sodium hydroxide solution and dichloromediane. The organic layer was dried (Na j SO 4 ) and evaporated in vacuo. The residue was triturated in dietiiyl ether, filtered and dried in vacuo at 60°C to afford die titie compound (0.06g, 36%) as a grey-green solid (mp 210-213°C) NMR (200 MHz; CDCl,) δ: 3.30 (2H, t, J=9), 3.87 (3H, s), 4.12 (2H, t, J=9), 6.56 (IH, s), 6.87 (IH, s), 7.29-7.58 (4H, m), 7.81 (IH, d, J=8), 8.21 (IH, s), 8.60 (IH, d, J=5), 8.69 (IH, d, J=3). MS (EI) m/z = 447 (M * ) Example 27 5-Methoxy-l-(5-methyl-(l^-4-oxadiazol-3-yl)-phenylcarbamoyl)-6- trifluoromethyl indoline (E27) Phenyl N-(5-Methyl-(l,2,4-oxadiazol-3-yl)phenyl)carbamate (D68) (0.23g, 0.00078 mole) in dry dimethylformamide (10 ml) was treated, under argon, with 5-methoxy- 6-trifluoromethylindoline (0.17g, 0.00078 mole) (Dl 1) and heated to 120°C for 4 hours. After cooling to ambient temperature, the solvent was removed in vacuo. The residue was partitioned between water and dichloromediane and the organic layer was dried N&fiO,) and evaporated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with 5% methanol/dichloromethane. The resulting solid was recrystallised from ethyl acetate/60-80° petroleum ether to leave the titie compound (0.1 lg, 34%) as a beige solid (mp 203-204°C) Η NMR (250 MHz; d'DMSO) δ: 2.68 (3H, s), 3.30 (2H, t, J=8), 3.85 (3H, s), 4.21 (2H, t, J=8), 7.21 (IH, s), 7.49 (IH, t, J=7), 7.66 (IH, d, J=7), 7.81 (IH, d, J=7), 8.16 (IH, s), 8.33 (IH, s), 8.82 (IH, s) MS (Electron Spray) m/z = 419 (MH * ) Example 28 l-[4-Methyl-3-(4-methyI-3-pyridyl)phenylcarbamoyl]-5-methoxy-6- trifluoromethyl indoline (E28) Phenyl N-(4-Methyl-3-(4-methylpyrid-3-yl)phenyl)carbamate (D69) (0.5g, 0.0016 mole) in dry dimethylformamide (20 ml) was treated widi 5-methoxy-6- trifluoromethylindoline (Dl 1) (0.34g, 0.0016 mole) under argon and heated to 100°C for 6 hrs. The mixture was allowed to cool and evaporated to dryness in vacuo. The residue was dissolved in dichloromediane and die solution washed with 10% aqueous sodium hydroxide solution (2 x 20 ml) and then with saturated aqueous sodium chloride solution (30ml). The organic phase was then dried (Na,SO 4 ) filtered and evaporated to dryness. The residue was purified by flash chromatography on silica gel eluting with 1% methanol/dichloromediane. Trituration of the resulting residue with dietiiyl ether gave the title compound (E28) (0.326g, 47%) m.p. 138-140° C. iH NMR (CDCl,) δ: 2.00 (3H, s), 2.13 (3H, s), 3.25 (2H, t, J=8Hz), 3.82 (3H, s), 4.12 (2H, t, J=8Hz), 6.62 (IH, s), 6.81 (IH, s), 7.11-7.29 (3H, m), 7.39-7.45 (IH, m), 8.20 (IH, s), 8.30 (IH, s), 8.44 (IH, d, J=6Hz) M.S. found 442 (MIT), C^H^O^IT requires 442 Example 29 l-[5-Bromo-3-(pyrid-3-yl)phenylcarbamoyI]-5-methoxy-6- trifluoromethylindoline (E29) The tide compound was prepared from phenyl N-[3-bromo-5-(pyrid-3- yl)phenyl]carbamate (D21) and 5-methoxy-6-trifluoromethylindoline (Dl l) using the metiiod of Example 28. iH NMR 250 MHz CDCl, δ: 8.74 (IH, s, Ar), 8.54 (dd, IH, Ar), 8.19 (s, IH, Ar), 7.88 (d, IH, Ar), 7.74 (s, IH, Ar), 7.6 (s, IH, Ar), 7.32-7.44 (m, 2H, Ar), 6.82 (br s, IH, Ar), 4.15 (t, 2H, indoline), 3.85 (s, 3H, Me), 3.25 (t, 2H, indoline) Example 30 l-[4-t-Butyl-3-(pyrid-3-yl)phenylcarbamoyl]-5-methoxy-6- trifluoromethylindoline (E30) The title compound (0.055g, 23%) was prepared from phenyl N-[4-t-butyl-3-(pyrid- 3-yl)phenyl]carbamate (D22) (0.18g, 0.00052 mole) and 5-methoxy-6- trifluoromethylindoline (Dll) using the method of Example 28. Η NMR (200 MHz, CDCl,) δ: 1.25 (9H,s), 3.27 (2H, t, J=ll), 3.85 (3H, s), 4.09 (2H, t, J=ll), 6.43 (IH, s), 6.85 (IH, s), 7.00 (IH, d, J=l), 7.18-7.35 (IH, m), 7.39- 7.69 (3H, m), 8.20 (IH, s), 8.42-8.69 (2H, m) MS (Electron Spray) m/z = 470 (MJT) Example 31 l-[4-Methoxy-3-(pyrid-3-yl)phenylcarbamoyl]-5-methoxy-6- trifluoromethylindoline (E31) The titie compound (0.21g, 32%) was prepared from phenyl N-[4-methoxy-3-(pyrid- 3-yl)phenyl]carbamate (D23) (0.48g, 0.0015 mole) and 5-methoxy-6- trifluoromethylindoline (D 11 ) using the method of Example 28. NMR (200 MHz, DTJMSO) δ: 3.26 (2H, t, J=9), 3.76 (3H, s), 3.83 (3H, s), 4.14 (2H, t, J=9), 7.10 (IH, d, J=7), 7.19 (IH, s), 7.45 (IH, dd, J=l,5), 7.54 (IH, s), 7.59 (IH, d, J=3), 7.87 (IH, dt, J=l,5), 8.10 (IH, s), 8.47-8.55 (2H, m), 8.67 (IH, d, J=3). MS (Electron Spray) m/z=444 (MIT) The mesylate salt can be prepared by treatment with methanesulphonic acid in acetone. Example 32 l-[5-Fluoro-4-methoxy-3-(pyrid-3-yl)phenylcarbamoyl]-5-methoxy-6- trifluoromethylindoline (E32) The tide compound (0.34g, 53%) was prepared from phenyl N-[5-fluoro-4-methoxy- 3-(pyrid-3-yl)phenyl)carbamate (D24) (0.48g, 0.0014 mole) and 5-methoxy-6- trifluoromethylindoline (Dll) using the metiiod of Example 28. NMR (200 MHz, DTJMSO) δ: 3.38 (2H, t, J=8), 3.68 (3H, s), 3.84 (3H, s), 4.17 (2H, t, J=8), 7.21 (IH, s), 7.43 (IH, s), 7.51 (IH, dd, J=5, 9), 7.66 (IH, dd, J=3, 20), 7.91 (IH, dt, J=l,8), 8.12 (IH, s), 8.61 (IH, dd, J=3,5), 8.70 (IH, d, J=3), 8.75 (IH, s). MS (Electron Spray) m/z=462 (MH * ) Example 33 l-[3-Bromo-4-methyI-5-(3-pyridyI)phenylcarbamoyl]-5-methoxy-6- trifluoromethylindoline (E33) A mixture of l-(3,5-dibromo-4-methylphenylcarbamoyl)-5-methoxy-6- trifluoromethylindoline (D25, 0.5 lg, 1 mmol), 3-pyridylboronic acid (0.12g, 1 mmol), tetrakis (triphenylphosphine)palladium (0) (35 mg, 0.03 mmol) and sodium carbonate (0.4 lg, 4 mmol) in dimetiioxyethane (30 mL) and water (3 mL) was heated under reflux, under argon, for 18 h. The mixture was cooled and poured into water. The precipitate was filtered off, washed witii water and dried. The crude product was chromatographed on silica gel, eluted with ethyl acetate, and die eluted material was triturated widi etiier to give the title compound (0.14g, 28%), m.p. 216-8°C. NMR (d 6 -DMSO) δ: 2.20 (3H, s), 3.25 (2H, t, J=8), 3.84 (3H, s), 4.15 (2H, t, J=8), 7.20 (IH, s), 7.50 (IH, s + IH, m), 7.82 (IH, d, J=7), 8.03 (IH, s), 8.11 (IH, s), 8.57 (IH, s), 8.62 (IH, d, J=4), 8.71 (IH, s). MS (API) m/z 506 (MIT, 79 Br), 508 (MH\ "Br) Example 34 l-[3-(4-Isoquinolyl)phenylcarbamoyI]-5-methoxy-6-trifluoromethyl indoline The title compound was prepared by die metiiod of Example 23, from 4-(3- aminophenyl)isoquinoline (0.41g, 1.9 mmol), l,r-carbonyldiimidazole (0.33g, 2 mmol) and 5-methoxy-6-trifluoromethylindoline (Dll) (0.41g, 1.9 mmol). Crude product was chromatographed on silica gel eluted witii 5% methanol/dichlorometiiane and eluted material was recrystallised from dichoromethane to give the title compound (0.22g, 25%), m.p. 211-5°C. NMR (d 6 -DMSO) δ: 3.28 (2H, t, J=8), 3.85 (3H, s), 4.21 (2H, t, J=8), 7.20 (IH, d, J=7), 7.22 (IH, s), 7.50 (IH, t, J=8), 7.76 (2H, m), 7.78 (IH, s), 7.82 (IH, t, J=7), 7.93 (lh, d, J=8), 8.1 (IH, s), 8.25 (IH, d, J=8), 8.47 (IH, s), 8.73 (IH, s), 9.38 (IH, s) Found: C, 67.01; H, 4.51; N, 9.03% CJ-J- 3 OJ- 3 requires C, 67.38; H, 4.35; N, 9.07% MS (API) 464 (MH * ) The mesylate salt can be prepared by treatment with medianesulphonic acid in acetone. Example 35 l-[5-(4-Methyl-3-pyridyl)-pyrid-3-ylcarbamoyl]-5-methoxy-6- trifluoromethylindoline (E35) 1 -[5-Bromo-(3-pyridylcarbamoyl]-5-methoxy-6-trifluoromethylindoline (D26) (0.3g, 0.7 mmoles) and 4-medιyl-3-pyridylboronic acid (0.12g, 0.9 mmoles) was heated under reflux in dimetiioxyetiiane (80 ml) and water (10 ml) with sodium carbonate (0.15g, 1.4 mmoles) and palladium tetrakis triphenylphosphine (O.lg, 12 mole %) under an inert atmosphere for 18 hours. After cooling the mixture was partitioned between ethyl acetate (250 ml) and water (200 ml). The organic layer was separated and washed with saturated sodium chloride solution then dried (Na^O . Evaporation of the solvent followed by flash chromatography on silica gel eluting with 3-7% MeOH/CH j Cl j and recrytallisation from ethyl acetate/60-80 petrol gave the title compound (E35) (0.2g, 65%) m.p. 125-8°C. iH NMR (CDCl,) δ: 2.32 (3H, s), 3.32 (2H, t, J=8Hz), 3.85 (3H, s), 4.18 (2H, t, J=8Hz), 6.90 (2H, s), 7.21 (IH, d, J=4Hz), 8.10 (IH, s), 8.18 (IH, s), 8.27 (IH, s), 8.40 (IH, s), 8.45-8.53 (2H, m). M.S. found m/z 429 (MIT) C^N, 0 ^ requires 429. Example 36 l-[6-(3-Pyridyl)-pyrid-3-ylcarbamoyl]-5-methoxy-6-trifluoromethylindoline Reaction of Phenyl N-[6-(pyrid-3-yl)pyrid-3-yl]carbamate (D27) (0.66g, 2.3 mmoles) with 5-methoxy-6-trifluoromethylindoline (Dll) (0.5g, 2.3 mmoles) as in the method of example 28 gave the title compound (E36) (0.73g, 78%) m.p. >270°C. iH NMR (DMSO-d*) δ: 3.32 (2H, t, J=8Hz), 3.88 (3H, s), 4.23 (2H, t, J=8Hz), 7.20 (IH, s), 7.45-7.55 (IH, m), 7.98-8.18 (3H, m), 8.35-8.43 (IH, m), 8.55-8.60 (IH, m), 8.85 (IH, d, J=4Hz), 8.91 (IH, s), 9.23 (IH, s). MS (API) found m z 415 (MH * ) C v H l ' ~ fi^. requires 415 Example 37 l-[5-(2-Furyl)-pyrid-3-ylcarbamoyl-5-methoxy-6-trifluoromethyl indoline (E37) This was prepared from l-(5-bromopvrid-3-ylcarbamoyl)-5-methoxy-6- trifluoromethyl indoline and 2-furylboronic acid by die same metiiod as for Example 10, affording the title compound as a pale brown crystalline solid in 80% yield, m.p. 92-94°C. NMR (D'-DMSO) 3.30 (2H, t), 3.85 (3H, s), 4.20 (2H, t), 6.65 (IH, m), 7.10 (IH, d), 7.25 (IH, s), 7.85 (IH, s), 8.15 (IH, s), 8.30 (IH, t), 8.60 (IH, d), 8.65 (IH, d), 8.90 (IH, bs). Example 38 l-[2-(4-Pyridyl)-thiazol-4-ylcarbamoyI-5-methoxy-6-trifluoromethyl indoline This was prepared from 2-(4-pyridyl)-tiiiazole-4-carboxylic acid by die same methodology as for Description 15 and Example 19, affording the title compound as a yellow crystalline solid in 8% overall yield, m.p. >220°C. NMR (D 6 -DMSO) 3.30 (2H, t), 3.85 (3H, s), 4.20 (2H, t), 7.20 (IH, s), 7.75 (IH, s), 7.90 (2H, d), 8.15 (IH, s), 8.70 (2H, d), 9.90 (IH, bs). Example 39 l-[2-(Pyrazinyl)-thiazol-4-ylcarbamoyI]-5-methoxy-6-trifluoromethyl-indoline This was prepared from 2-pyrazinyl-thiazole-4-carboxylic acid by die same methodology as for Description 15 and Example 19, affording the tide compound as a yellow crystalline solid in 45% overall yield, m.p. >240°C. NMR (D 6 -DMSO) 3.30 (2H, t), 3.85 (3H, s), 4.20 (2H, t), 7.20 (IH, s), 7.75 (IH, s), 8.20 (IH, s), 8.75 (2H, m), 9.30 (IH, s), 9.90 (IH, s) Example 40 l-[3-(5-Pyrimidyl)phenylcarbamoyl]-5-methoxy-6-trifluoromethyl-indoline This was prepared from 3-(5-pyrimidyl)-aniline (D29) and 5-methoxy-6- trifluoromethyl-indoline (Dll), according to the metiiod of Example 1, affording die tide compound in 69% yield as a white crystalline solid, m.p. 226-8°C. NMR (D 6 -DMSO) 3.30 (2H, t), 3.85 (3H, s), 4.20 (2H, t), 7.20 (IH, s), 7.45 (2H, m), 7.70 (IH, m), 7.95 (IH, s), 8.15 (IH, s), 8.70 (IH, s), 9.10 (2H, s), 9.20 (IH, s) Example 41 l-[3-(4-MethyI-3-pyridyl)phenylcarbamoyl]-5-methoxy-6- trifluoromethylindoline Reaction of phenyl-N-[3-(4-methylpyrid-3-yl)phenyl]carbamate (D28) (0.4g, 1.3 mmoles) with 5-methoxy-6-trifluoromethylindoline (Dll) (0.28g, 1.3 mmoles) as in the method of Example 28 gave the titie compound (E41) (0.19g, 34%) m.p. 178- 180°C. iH NMR (DMSO-d 6 ) δ: 2.29 (3H, s), 3.29 (2H, t, J=8Hz), 3.84 (3H, s), 4.19 (2H, t, J=8Hz), 7.01 (IH, d, J=6Hz), 7.20 (IH, s), 7.31-7.43 (2H, m), 7.55-7.62 (2H, m), 8.10 (IH, s), 8.32 (IH, s), 8.40 (IH, d, J=6Hz), 8.62 (IH, s). M.S. (API) found m/z 428 (MH * ) C^H^N j O^, requires 428 Example 42 l-[5-EthyI-3-(pyrid-3-yl)phenylcarbamoyl]-5-methoxy-6-trifluoromethylindoline The title compound (0.15g, 40%) was prepared as a tan powder using the methodology of Example 28 from phenyl N-(3-ethyl-5-(pyrid-3-yl)phenyl carbamate (D30) (0.26g, 0.81 mmol) and 5-methoxy-6-trifluoromethyl indoline (Dl l) (0.177g, 0.81 mmol) in DMF (10 ml). Melting point: 205°C-207°C iH NMR 250 MHz, CDCl, δ: 8.81 (s, IH, Ar), 8.58 (d, IH, Ar), 8.22 (s, IH, Ar), 7.88 (m, IH, Ar), 7.48 (s, IH, Ar), 7.32 (m, 2H, Ar), 7.12 (s, IH, Ar), 6.85 (s, IH, Ar), 6.52 (s, IH, NH), 4.12 (t, 2H, indoline), 3.88 (s, 3H, Me), 3.28 (t, 2H, indoline), 2.60 (q, 2H, CH,), 1.3 (t, 3H, Me). Mass spec, m/z = 442 [M * l] * Example 43 5-Methoxy-l-[5-phenyl-3-(pyrid-3-yl)phenylcarbamoyl]-6-trifluoromethyl indoline (E43) The tide compound (0.74g, 47%) was prepared as an off white solid using the methodology of example 28, with phenyl N-(5-phenyl-3-(pyrid-3- yl)phenyl)carbamate (D31) (0.27g, 0.76 mmol) and 5-methoxy-6-trifluσromethyl indoline (Dl 1) [0.182 mg, 0.83 mmol) in DMF (10 ml). Melting point: 150°-151°C iH NMR 250 MHz CDCl, δ: 8.87 (s, IH, Ar), 8.60 (d, IH, Ar), 8.24 (s, IH, Ar), 7.90 (m, IH, Ar), 7.70-7.55 (m, 4H, Ar), 7.50-7.30 (m, 5H, Ar), 6.85 (br, IH, Ar), 6.65 (br, IH, NH), 4.12 (t, 2H, indoline), 3.85 (3H, s, Me), 3.28 (t, 2H, indoline) Example 44 6-Chloro-5-methyl-l-[4-methyI-3-(4-methyl-3-pyridyl)phenyl carbamoyl] indoline Reaction of phenyl N-[4-methyl-3-(4-metiιylpyrid-3-ylphenyl)carbamate (D69) (0.5g, 1.6 mmoles) with 6-chloro-5-methylindoline (see WO 95/01976) (0.26g, 1.6 mmoles) as in the method of Example 28 gave the titie compound (E44) (0.23g, 38%) m.p. 178-180°C. iH NMR (CDCl,) δ: 2.01 (3H, s), 2.12 (3H, s), 2.29 (3H, s), 3.15 (2H, t, J=8Hz), 4.07 (2H, t, J=8Hz), 6.60 (IH, s), 6.95 (IH, s), 7.15-7.28 (3H, m), 7.38-7.43 (IH, m), 7.95 (IH, s), 8.30 (IH, s), 8.42 (IH, s) MS (API) found m/z 392 (MH\ M C1), 394 (MH * , "Cl) C^H^N j OCl requires 392, 394 Example 45 l-[3-(pyrid-3-ylaminocarbonyI)-phenylcarbamoyl]-5-methoxy-6-trifluoromethyI- indoline A mixture of 3-(3-aminobenzoylamino)pyridine (D33) (0.416g, 2 mmol) and carbonyl diimidazole (0.34g, 2 mmol) in dichloromedιane/N,N-dimethylformamide (25 ml/0.25 ml) was heated to reflux for 0.25 h, then evaporated to dryness. The residue was dissolved in N,N-dimethylformamide (15 ml) and 5-metiιoxy-6- trifluoromethyl indoline (0.416 g, 2 mmol) was added. The mixture was heated to 100° C for 1 h then treated with water (30 ml). Filtration and drying afforded a white solid (0.5 g). Chromatography on silica eluting with a gradient of 0-20% methanol in ethyl acetate afforded die title compound as a white solid (0.17g, 19%), m.p. >220° C. iH NMR (D6-DMSO) 3.25 (2H, t, J 8 Hz), 3.85 (3H, s), 4.20 (2H, t, J 8 Hz), 7.25 (IH, s), 7.40-7.55 (2H, m), 7.65 (2H, d, J 8 Hz), 7.90 (IH, d, J 8 Hz), 8.10-8.30 (3H, m), 8.40 (IH, d, J 2 Hz), 8.10-8.30 (3H, m), 8.40 (IH, d, J 2 Hz), 8.85 (IH, s), 8.90 (IH, d, J 2 Hz), 10.50 (IH, s). m/e 457 [MH] Θ C23H19N4F3O3 requires 457 Example 46 l-[3-(Pyrid-3-ylaminocarbonyl)-phenylcarbamoyI]-5-methylthio-6- trifluoromethyl-indoline To a suspension of 5-methylthio-6-trifluoromethyl-l-(3-carboxy phenyl carbamoyl)indoline (D36) (0.5g, 1.25 mmol) in dichloromethane was added oxalyl chloride (0.324g, 2.5 mmol) and dimediylformamide (3 drops). After effervescence had subsided die reaction mixture was evaporated under reduced pressure before being dissolved in tetrahydrofuran (10 ml) and added dropwise to a solution of 3- aminopyridine (0.133 mg, 1.4 mmol) and triethylamine (0.141g, 1.4 mmol) in tetrahydrofuran (10 ml) at 0° C. After 1 hour water was added forming a white precipitate which was filtered and dried to yield die product as a white solid (0.435g, 73%), mp 195-7° C. iH NMR (DMSO) δ: 10.5 (IH, s); 9.0 (2H, d, J5Hz); 8.4 (IH, d, J5Hz); 8. (IH, s); 8.25 (IH, s); 8.2 (IH, s); 7.9 (IH, d, J7Hz); 7.7 (IH, d, J7Hz); 7.5 (3H, m); 4.3 (2H, t, J8Hz); 3.3 (2H, t, J8Hz); 2.5 (3H, s) Example 47 l-[3-(Pyrid-4-ylaminocarbonyl)-phenylcarbamoyl]-5-methylthio-6- trifluoromethyl indoline This was made in the same manner as Example 46 using a solution of 4-aminopyridine to give the product as a peach solid (0.45g, 76%), mp >200° C. iH NMR (DMSO) δ: 10.7 (IH, s); 8.95 (IH, s); 8.5 (2H, d, J7Hz); 8.2 (IH, s); 8.1 (IH, s); 7.85 (IH, d, J7Hz); 7.8 (2H, d, J7Hz); 7.65 (IH, d, J7Hz); 7.45 (2H, m); 4.25 (2H, t, J7Hz); 3.3 (2H, t, J7Hz); 2.5 (3H, s) m/e = 472 C23H19F3N4O2S requires 472 Example 48 l-[4-(Pyrid-3-ylaminocarbonyl)-phenylcarbamoyI]-5-methylthio-6- trifluoromethyl indoline This was made in the same manner as Example 46 using 5-methylthio-6- trifluoromethyl-l-(4-carboxy phenyl carbamoyl) indoline (D37) to give the product as a pale yellow solid (0.327g, 55%), mp >200 °C. iH NMR (DMSO) δ: 10.6 (IH, s); 9.1 (IH, s); 9.0 (IH, s); 8.4 (2H, d, J7Hz); 8.2 (IH, s); 8.0 (2H, d, J7Hz); 7.8 (2H, d, J7Hz); 7.6 (IH, q, J5Hz); 7.4 (IH, s); 4.25 (2H t, J7Hz); 3.3 (2H, t, J7Hz); 2.5 (3H, s). m/e = 472 C23H19F3N4O2S requires 472 Example 49 l-[4-(Pyrid-4-yIaminocarbonyl)-phenylcarbamoyl]-5-methylthio-6- trifluoromethyl indoline This was made in die same manner as Example 48 using a solution of 4- aminopyridine to give the product as an orange solid (0.352g, 59%), mp 158-160° C. iH NMR (DMSO) δ: 10.5 (IH, s); 8.95 (IH, s); 8.5 (2H, d, J5Hz); 8.2 (IH, s); 7.9 (2H, d, J7Hz); 7.85 (2H, d, J5Hz); 7.8 (2H, d, J7z); 7.5 (IH, s); 4.25 (2H, t, J7Hz); 3.3 (2H, t, J7Hz); 2.5 (3H, s). m/e = 472 C23H19F3N4O25 requires 472 Example 50 l-[3-(3-pyridylcarbonyl)phenylcarbamoyl]-5-methoxy-6-trifluoromethyl indoline The title compound (0.17g, 26%) was prepared using the method of Example 45, and purified by flash column chromatography on silica gel, eluting with 2% methanol/dichloromethane, and recyrstallisation from ethylacetate/methanol/60-80 o petroleum ether. iH NMR (200 MHz; D^DMSO) δ: 3.28 (2H, t), 3.75 (3H, s), 4.20 (2H, t), 7.22 (IH, s), 7.38-7.49 (IH, m), 7.52 (IH, t), 7.63 (IH, q), 7.93-8.00 (IH, m), 8.02 (IH, d), 8.08-8.20 (2H, m), 8.78-8.99 (2H, m), 9.02 (IH, d) Example 51 l-[3-(Pyrid-3-yl-aminosuIphonyl)-phenylcarbamoyl]5-methoxy-6- trifluoromethyl-indoline A suspension of 3-(pyrid-3-ylam_Lnosulphonyl)-aminobenzene (D39) (0.5g, 2 mmol) in chloroform (40 ml) was treated with triethylamine (5 ml) and chlorotrimethylsilane (5 ml). The solution was evaporated to dryness, and the residue dissolved in dichloromediane (20 ml). Carbonyl diimidazole (0.32g, 2 mmol) was added and after 1 h die reaction mixture was evaporated to dryness. Dimethylformamide (20 ml) and 5-methoxy-6- trifluoromethyl indoline (0.43g, 2 mmol) was added, and die mixture heated to 100° C for 2 h. The cooled solution was diluted widi water (60 ml). Filtration and drying afforded a brown solid (0.6g). Chromatography, eluting with 0- 5% methanol in ethyl acetate afforded die product as a white solid (0.26g, 26%), m.p. >215° C. iH NMR (DMSO) δ: 10.60 (IH, s), 8.9 (IH, s), 8.30 (IH, d, J2Hz), 8.25 (IH, dd, J5Hz, 2Hz), 8.20 (IH, t, J2Hz), 8.10 (IH, s), 7.80 (IH, d, J7Hz), 7.35-7.55 (3H, m), 7.30 (IH, m), 7.20 (IH, s), 4.20 (2H, t, J8Hz), 3.85 (3H, s), 3.25 (2H, t, J8Hz) Example 52 5-Methylthio-6-trifluoromethyl-l-[6-(pyridin-3-yloxy)pyridin-3- ylcarbamoyl)]indoIine 5-Amino-2-(pyridin-3-yloxy)pyridine (0.5g, 2.7 mmol) in dichloromediane (25 ml) was treated witii triethylamine (0.4 ml, 2.9 mmol) then phenyl chloroformate (0.34 ml, 2.7 mmol) dropwise at -20°C. The reaction mixture was allowed to warm to room temperature over 1 hour then poured into dilute aqueous sodium bicarbonate (50 ml). The organic phase was separated and die aqueous phase extracted with dichloromethane (2 x 50 ml). The combined organic phases were dried (Na j SO 4 ) and evaporated to give the crude phenyl carbamate (0.84g) as a crystallising oil. This material was taken-up in dry DMF (10 ml) and triethylamine (0.5 ml) and treated widi 5-medιyltiιio-6-trifluoromethyl indoline hydrochloride (0.63g, 2.32 mmol) at 100°C for 0.5 h. After cooling the DMF was removed under reduced pressure and the residue was partitioned between 5% aqueous sodium hydroxide (100 ml) and dichloromediane (3 x 100 ml). The combined organic extracts were dried (Na^SO and evaporated. Chromatography using 2% methanol in ethyl acetate as eluant followed by recrystallisation from ethyl acetate/petroleum ether (60-80°) gave the title compound (0.88g, 73%) as a white crystalline solid m.p. 193-4°C. NMR (250 MHz, DMSO) δ: 3.28 (2H, t, J 8Hz), 3.37 (3H, s), 4.20 (2H, t, J 8Hz), 7.13 (IH, d, J 9Hz), 7.42-7.51 (2H, m), 7.61 (IH, m), 8.08 (IH, dd, J 8Hz, 2 Hz), 8.21 (IH, s), 8.27 (IH, d, J 2Hz), 8.40-8.48 (2H, m), 8.86 (IH, s). MS (El) m/e = 447 (MIT) Example 53 5-Methoxy-6-trifluoromethyl-l-[6-(pyridin-3-yloxy)pyridin-3- ylcarbamoyI]indoline 5-Amino-2-(pyridin-3-yloxy)pyridine (0.2g, 1.1 mmol) was treated with phenyl chloroformate to give the phenyl carbamate which was treated with 5-methoxy-6- trifluoromethylindoline (0.23g, 1.1 mmol) according to the method of Example 52 to give die titie compound (0.34g, 74%) as a white solid m.p. 202-4°C. NMR (250 MHz, DMSO) δ: 3.28 (2H, t, J 8Hz), 3.86 (3H, s), 4.18 (2H, t, J 8Hz), 7.12 (IH, d, J 9Hz), 7.22 (IH, s), 7.47 (IH, dd, J 7Hz, 5Hz), 7.51 (IH, m, J 7Hz), 8.08 (IH, dd, J 8Hz, 2Hz), 8.10 (IH, s), 8.27 (IH, d, J 2Hz), 8.40-8.47 (2H, m), 8.78 (IH, s). MS (El) m/e = 431 (MIT) Example 54 5-Methoxy-6-trifluoromethyI-l-[4-(pyridin-4-ylmethyloxy)phenyI carbamoyl]indoline 4-(Pyridin-4-ylmetiιyloxy)aniline (0.5g, 2.5 mmol) was converted to die phenyl carbamate and treated with 5-methoxy-6-trifluoromethylindoline (0.54g, 2.5 mmol) as in the method of Example 52. Chromatography using ethyl acetate as eluant followed by recrystallisation from ethyl acetate/petroleum ether (60-80°) afforded die title compound (0.23g, 24%) as an off-white crystalline solid m.p. 205-207°C. Η NMR (250 MHz, CDCl,) δ: 3.26 (2H, t, J 8Hz), 3.82 (3H, s), 4.07 (2H, t, J 8Hz), 5.06 (2H, s), 6.29 (IH, s), 6.83 (IH, s), 6.91 (2H, d, J 10Hz), 7.28-7.48 (4H, m), 8.22 (IH, s), 8.60 (2H, d, J 7Hz). MS (El) m/e = 444 (MIT) Example 55 5-Methoxy-6-trifluoromethyl-l-[6-(pyridin-4-ylmethyloxy)pyridin-3- ylcarbamoyl]indoline 5-Amino-2-(pyridin-4-ylmethyloxy)pyridine (0.5g, 2.5 mmol) was converted to the phenyl carbamate and treated widi 5-methoxy-6-trifluoromethylindoline (0.54g, 2.5 mmol) as in the method of Example 52. Chromatography using ethyl acetate as eluant followed by recrystallisation from ethyl acetate/petroleum ether (60-80°) afforded the titie compound (0.13g, 13%) as an off-white solid m.p. 187-189°C. NMR (250 MHz, CDCl,) δ: 3.31 (2H, t, J 8Hz), 3.88 (3H, s), 4.12 (3H, t, J 8Hz), 5.40 (2H, s), 6.32 (IH, s), 6.88 (IH, m), 7.35 (2H, d, J 6Hz), 7.91 (IH, dd, J 8Hz, 2Hz), 8.04 (IH, d, J 2Hz), 8.22 (IH, s), 8.59 (2H, d, J 6Hz) MS (El) m/e = 445 (MIT) Example 56 5-Methylthio-6-trifluoromethyl-l-[4-(pyrid-4-yl-methylamino carbonyl)phenyl carbamoyl]indoline This was prepared by die same methodology as for Example 69 affording the title compound in 11% yield as a white solid. m.p. 230-2°C. iH NMR (D6-DMSO) 2.50 (3H, s), 3.25 (2H, t), 3.45 (3H, s), 4.20 (2H, t), 7.15 (2H, d), 7.25 (2H, d), 7.50 (3H, m), 8.20 (IH, s), 8.45 (2H, d), 8.80 (IH, s) Example 57 Trans-5-Methylthio-6-trifluoromethyl-l-{4-[2-ethenyl-(4-pyridyl)]-phenyl carbamoyU-indoline This was prepared from trans-4-[2-ethenyl-(4-pyridyl)]-aniline (D43) and 5- methyltiιio-6-trifluoromethyl indoline (D7) using the phenyl chloroformate procedure as for Description 18 and Example 26 affording die title compound as a yellow solid in 18% yield, m.p. 157 -9°C. iH NMR (D6-DMSO) 2.50 (3H, s), 3.30 (2H, t), 4.25 (2H, t), 7.15 (IH, d), 7.45 (IH, s), 7.55 (2H, d), 7.65 (5H, m), 8.25 (IH, s), 8.55 (2H, d), 8.80 (IH, s) Example 58 5-Methylthio-6-trifluoromethyl-l-{4-[2-ethyl(4-pyridyI)]phenyl carbamoyl}indoline This was prepared by hydrogenation of D42 followed by coupling with 5-methylthio- 6-trifluoromethyl indoline (D7) using the phenyl chloroformate method, affording die title compound in 20% yield as a white solid, m.p. 158-161°C. iH NMR (DMSO) 2.50 (3H, s), 2.85 (4H, m), 3.25 (2H, t), 4.20 (2H, t), 7.15 (2H, d), 7.25 (2H, d), 7.45 (4H, m), 8.20 (IH, s), 8.45 (2H, d), 8.60 (IH, s). Example 59 l-(l-(4-Pyridyl)-5-indolylcarbamoyl)-5-methoxy-6-trifluoromethylindoline The titie compound was prepared by the method of Example 73, from aminoindole (D53). Yield 62%, m.p. 206-211°C iH NMR (CDCl,) δ: 3.29 (2H, t, J=8), 3.85 (3H, s), 4.20 (2H, t, J=8), 6.78 (IH, d, J=3), 7.20 (IH, s), 7.41 (IH, dd, J=8,2), 7.72 (2H, d, J=6), 7.78 (IH, d, J=8), 7.83 (IH, d, J=3), 7.92 (IH, d, J=2), 8.16 (IH, s), 8.58 (IH, s), 8.70 (2H, d, J=6) MS(API) m/z=453(MH * ) Example 60 5-Methoxy-6-trifluoromethyl-l-[4-(pyridin-4-yIthiomethyl)phenyl carbamoyI]indoline 4-(Pyridin-4-yldιiomedιyl)aniline (0.37g, 1.71 mmol) was converted to die phenylcarbamate and treated widi 5-methoxy-6- trifluoromethylindoline (Dll) (0.37g, 1.71 mmol) as in the method of Example 26 to give the tide compound (0.5g, 64%) as a white crystalline solid m.p. 174-5°C. NMR (250 MHz; DMSO) δ: 3.26 (2H, t, J 8Hz), 3.84 (3H, s), 4.16 (2H, t, J 8Hz), 4.32 (2H, s), 7.20 (IH, s), 7.32 (2H, d, J 7Hz), 7.37 (2H, d, J 8Hz), 7.52 (2H, d, J 8Hz), 8.11 (IH, s), 8.37 (2H, d, J 7Hz), 8.58 (IH, s). MS(EI) m/e = 460 (MH + ) Example 61 5-Methoxy-6-trifluoromethyl-l-[4-(pyridin-4-ylsulphonylmethyl) phenylcarbamoyl]indoline 4-(Pyridin-4-ylsulphonylmethyl)aniline was converted to die titie compound according die metiiod of Example 60 to give a white crystalline solid (46%) m.p. 240- 242°C. Η NMR (250 MHz; DMSO) δ: 3.26 (2H, t, J 8Hz), 3.84 (3H, s), 4.17 (2H, t, J 8Hz), 4.77 (2H, s), 7.08 (2H, d, J 8Hz), 7.20 (IH, s), 7.50 (2H, d, J 8Hz), 7.70 (2H, d, J 7Hz), 8.10 (IH, s), 8.59 (IH, s), 8.88 (2H, d, J 7Hz) MS (El) m/e = 492 (MH * ) Example 62 5-Methoxy-6-trifluoromethyl-l-[4-(pyridin-4-ylmethylthio)phenyI carbamoyljindoline 4-(Pyridin-4-ylmethyldιio)aniline was converted to die titie compound according to the method of Example 60 to give a white crystalline solid (63%) m.p. 160-3°C. Η NMR (250 MHz; CDCl,) δ: 3.27 (2H, t, J 8Hz), 3.85 (3H, s), 3.95 (2H, s), 4.08 (2H, t, J 8Hz), 6.41 (IH, s), 6.84 (IH, s), 7.12 (2H, d, J 7Hz), 7.23 (2H, d, J 8Hz), 7.33 (2H, d, J8Hz), 8.21 (IH, s), 8.48 (2H, d, J 7Hz). MS (El) m/e = 460 (MH * ) Example 63 5-Methylthio-6-trifluoromethyl-l-[(6-phenoxy)-3-pyridylcarbamoyl]-indoline This was prepared from 6-phenoxy-3-aminopyridine and 5-methylthio-6- trifluoromethylindoline (D7) by similar methodology to Example 1, affording the title compound as a yellow solid in 39% yield, m.p. 86-88°C. NMR (D6-DMSO) 2.50 (3H, s), 3.30 (2H, t), 4.20 (2H, t), 7.00 (IH, d), 7.10 (2H, m), 7.20 (IH, m), 7.45 (3H, m), 8.05 (IH, d), 8.20 (IH, s), 8.30 (IH, d), 8.85 (IH, s). Example 64 5-Methoxy-6-trifluoromethyl-l-[2-(pyridin-3-yloxy)pyridin-4- ylcarbamoyl)]indoline 4-Amino-2-(pyridin-3-yloxy)pyridine (D45) was converted to the title compound by the method of Example 60 to give an off-white crystalline solid (89%) m.p. 223-5°C. NMR (250 MHz; DMSO) δ: 3.28 (2H, t, J 8Hz), 3.86 (3H, s), 4.21 (2H, t, J 8Hz), 7.24 (IH, s), 7.39 (IH, s), 7.40-7.52 (2H, m), 7.62 (IH, m, J 9Hz), 7.97 (IH, d, J 7Hz), 8.13 (IH, s), 8.40-8.48 (2H, m), 9.10 (IH, s). MS (El) m/e = 431 (MH * ) Example 65 5-Methylthio-6-trifluoromethyl-l-l6-(2-methylpyridin-3-yloxy) pyridin-3- ylcarbamoyl]indoline 5-Ammc>-2-(2-methylpyridin-3-yloxy)pyridine was converted to die title compound according to the method of Example 60 to give a pale yellow solid (30%) m.p. 204- 7°C. Η NMR (250 MHz; DMSO) δ: 3.28 (2H, t, J 8Hz), 3.34 (3H, s), 4.19 (2H, t, J 8Hz), 7.10 (IH, d, 8 Hz), 7.31 (IH, dd, J 8Hz, 5Hz), 7.44-7.53 (2H, m), 8.06 (IH, dd, J 8Hz, 2Hz), 8.21 (IH, s), 8.32 (2H, d, J 5Hz), 8.82 (IH, s). MS (El) m/e = 461 (MH * ) Example 66 5-Methylthio-6-trifluoromethyl-l-[6-(6-methylpyridin-3-yloxy)pyridin-3- ylcarbamoyl]indoline 5-An__ino-2-(6-methylpyridin-3-yloxy)pvridine was converted to die title compound according to die metiiod of Example 60 to give an off-white solid (44%) m.p. 206- 8°C. NMR (250 MHz; DMSO) δ: 3.28 (2H, t, J 8Hz), 3.37 (3H, s), 4.19 (2H, t, J 8Hz), 7.09 (IH, d, J 7Hz), 7.32 (IH, d, J 7Hz), 7.45-7.53 (2H, m), 8.06 (IH, dd, J 7Hz, 2Hz), 8.20 (IH, s), 8.24 (IH, d, J 2Hz), 8.30 (IH, d, J 2Hz), 8.84 (IH, s). MS (ED m/e = 461 (MIT) Example 67 5-Methoxy-6-trifluoromethyl-l-[6-(pyridin-3-ylthio)pyridin-3- ylcarbamoyl]indoline 5-Amino-2-(pyridin-3-ylthio)pyridine was converted to die title compound according to the mediod of Example 60 to give a white crystalline solid (51%) m.p. 208-210°C. NMR (250 MHz; DMSO) δ: 3.28 (2H, t, J 8Hz), 3.85 (3H, s), 4.17 (2H, t, J 8Hz), 7.20 (IH, d, J 7Hz), 7.22 (IH, s), 7.49 (IH, dd, J 7Hz, 5Hz), 7.90-7.99 (2H, m), 8.11 (IH, s), 8.57-8.68 (3H, m), 8.84 (IH, s). MS(EI) m/e = 447 (MH * ) Example 68 5-Methylthio-6-trifluoromethyl-l-[4-(pyrid-3-ylmethyl)amido phenyl carbamoyl]indoIine This was prepared in 61% yield by die same method as for Example 69, m.p. >250° C. iH NMR (D6-DMSO) δ: 2.50 (3H, s), 3.30 (2H, t), 4.25 (2H, t), 4.50 (2H, d), 7.40 (IH, m), 7.50 (IH, s), 7.70 (3H, m), 7.85 (2H, d), 8.25 (IH, s), 8.45 (IH, m), 8.55 (IH, m), 8.80 (IH, s), 9.00 (IH, t) Example 69 5-Methylthio-6-trifluoromethyI-l-[3-(pyrid-4-ylmethyI) amidophenylcarbamoyl] indoline A suspension of 5-methylti_io-6-trifluoromethyl-l-(3-carboxyphenyl carbamoyl) indoline (D55) (0.5g, 1.26 mmol) in dichloromethane (10 ml) was treated widi oxalyl chloride (0.2 ml, 0.3g, 2.4 mmol) and N,N-dimethyl formamide (3 drops). After lh the reaction mixture was evaporated to dryness. The residue was dissolved in tetrahydrofuran (20 ml) and added to a solution of 4-aminomethyl pyridine (0.15 ml, 1.39 mmol) and triethylamine (0.2 ml, 0.15g, 1.5 mmol) in tetrahydrofuran (10 ml) at 0°C. After 1 h 5M aqueous sodium hydroxide solution (5 ml) was added, followed by water (20 ml). Filtration and drying afforded the product as a yellow solid (0.58g, 94%) m.p. 122-3°C. iH NMR (D6-DMSO) δ: 2.50 (3H, s), 3.30 (2H, t), 4.20 (2H, t), 4.50 (2H, d), 7.30 (2H, d), 7.40 (IH, t), 7.45 (IH, s), 7.60 (IH, d), 7.80 (IH, d), 8.05 (IH, s), 8.25 (IH, s), 8.50 (2H, d), 8.85 (IH, bs), 9.15 (IH, t) Example 70 5-Methylthio-6-trifluoromethyl-l-[4-(pyrid-2-ylmethyl) amidophenylcarbamoyl] indoline This was prepared by die same method as for Example 69, affording the title compound as a white solid in 84% yield, m.p. 203-5°C. iH NMR (D6-DMSO) δ: 2.50 (3H, s), 3.30 (2H, t), 4.20 (2H, t), 4.55 (2H, d), 7.25- 7.35 (2H, m), 7.45 (IH, s), 7.65-7.75 (3H, m), 7.90 (2H, d), 8.25 (IH, s), 8.50 (IH, d), 8.85 (lH, s), 9.00 (lH, t). Example 71 l-(l-(3-Pyridylmethyl)-5-indolylcarbamoyl)-5-methoxy-6- trifluoromethylindoline A solution of aminoinde (D48, 0.40g, 1.8 mmol) and 1 , 1 '-carbonyldiimidazole (0.30g, 1.8 mmol) in dichloromethane (40 L) was stirred at room temperature for 1.75 h, then evaporated. To die residue was added dimethylformamide (DMF, 10 mL) and a solution of 5-methoxy-6-trifluσromethylindoline (Dll, 0.39g, 1.8 mmol) in DMF (5mL). The mixture was stirred at 110°C overnight, then poured into water and extracted with dichloromethane. The extract was washed witii water, dried and evaporated. The residue was triturated widi etiier to give a grey solid, which was recrystallised from dichloromethane/methanol to give the title compound (0.15g, 18%) m.p. 243-6°C. iH NMR (CDCl,) δ: 3.26 (2H, t, J=8), 3.83 (3H, s), 4.17 (2H, t, J=8), 5.45 (2H, s), 6.45 (IH, d, J=3), 7.19 (IH, s), 7.22 (IH, d, J=8), 7.33 (IH, dd, J=7,5), 7.42 (IH, d, J=8), 7.51 (IH, d, J=3), 7.5 (IH, d, J=8), 7.72 (IH, s), 8.12 (IH, s), 8.41 (IH, s), 8.46 (lH, d, J=5), 8.51 (lH, s) MS(API) m/z=467 (MIT) Example 72 l-(l-(4-Pyridylmethyl)-5-indolylcarbamoyl)-5-methoxy-6- trifluoromethylindoline A mixture of aminoindole (D49, 0.46g, 2.1 mmol), phenyl chloroformate (0.26 mL, 2.1 mmol) and triethylamine (0.29 mL, 2.1 mmol) in dichloromediane (5 mL) was stirred at room temperature for 1 h. The mixture was then diluted widi dichloromediane, washed with water, dried and evaporated. The residue was dissolved in acetonitrile (10 mL). 5-Methoxy-6-trifluoromethylindoline (Dll, 0.45g, 2.1 mmol) and triethylamine (0.29 mL, 2.1 mmol) were added and the mixture was stirred for 3h at room temperature. The reaction was worked up as for Example 71, and the solid obtained after trituration was recrystallised from dichloromethane/petrol to give the title compound (0.26g, 27%), m.p. 215-8°C. iH NMR (CDCl,) δ: 3.26 (2H, t, J=8), 3.83 (3H, s), 4.16 (2H, t, J=8), 5.48 (2H, s), 6.49 (IH, d, J=3), 7.04 (2H, d, J=6), 7.20 (2H, m), 7.30 (IH, d, J=8), 7.49 (IH, d, J=3), 7.73 (IH, s), 8.12 (IH, s), 8.42 (IH, s), 8.47 (2H, d, J=6). MS(API) m/z=467(MH * ) Example 73 l-(l-(3-pyridyl)-5-indolylcarbamoyl)-5-methoxy-6-trifluoromethyl indoline The titie compound was prepared by die metiiod of Example 72, from aminoindoline (D52, 0.34g, 1.63 mmol). Addition of the reaction mixture to water gave a precipitate which was filtered off, dried and recrystallised from dichloromethane/petrol to give die title compound (0.6 lg, 84%), m.p. 202-4°C. iH NMR (CDCl,) δ: 3.28 (2H, t, J=8), 3.84 (3H, s), 4.19 (2H, t, J=8), 6.73 (IH, d, J=3), 7.21 (IH, s), 7.38 (IH, dd, J=8,2), 7.55 (IH, d, J=8), 7.62 (IH, dd, J=7,5), 7.73 (IH, d, J=3), 7.89 (IH, d, J=2), 8.09 (IH, d, J=7), 8.17 (IH, s), 8.55 (IH, s), 8.60 (IH, d, J=5), 8.89 (IH, d, J=2). MS(API) m/z=453(MH * ) Example 74 5-Methylthio-6-trifluoromethyl-l-{3-[2-(3-pyridyl)thiazol-4- yl]phenylcarbamoyl} indoline A solution of 4-(3-aminophenyl)-2-(3-pyridyl)-tiιiazole (0.76g, 3 mmol) in chloroform (30 ml) was added to a solution of carbonyl diimidazole (0.49g, 3 mmol) in dichloromethane (10 ml). After 1 h the mixture was evaporated. 5-Methylthio-6- trifluoromethyl indoline (0.7g, 3 mmol) and N,N-dimethylformamide (20 ml) were added. The mixture was heated at 100°C for lh, then diluted widi water (50 ml). Filtration and evaporated afforded a yellow solid (l.lg). Recrystallisation from ethyl acetate-petrol afforded the title compound as a white solid (0.53g, 35%), m.p. 154- 5°C. iH NMR (DMSO) 2.50 (3H, s), 3.30 (2H, t), 4.25 (2H, t), 7.45 (IH, t), 7.50 (IH, s), 7.55 (2H, m), 7.70 (IH, m), 8.25 (2H, m), 8.40 (IH, dt), 8.70 (IH, d), 8.80 (IH, s), 9.25 (IH, d). Example 75 5-Methylthio-6-trifluoromethyl-l-{4-[2-(4-pyridyl)-thiazol-4-yl]phenyl carbamoyl}indoline This was prepared in die same manner as 5-methyltiιio-6-trifluoromethyl-l-{3-[2-(3- pyridyl)-tiιiazol-4-yl]phenyl carbamoyl } indoline to give the product as a yellow solid (0.2g, 31%), m.p. 253-4° C. Η NMR (DMSO) δ: 8.8 (3H, m), 8.2 (2H, s), 8.0 (4H, m), 7.7 (2H, d), 7.4 (IH, s), 4.2 (2H, t), 3.3 (2H, t), 2.5 (3H, s) Example 76 5-Methylthio-6-trifluoromethyl-l-{4-[2-(3-pyridyl)-thiazol-4- yI]phenylcarbamoyI}indoline This was prepared in the same manner as 5-methylthio-6-trifluoromethyl-l-{3-[2-(3- pyridyl)-tiιiazol-4-yl]phenyl carbamoyl) indoline to give the product as a yellow solid (0.25g, 39%), m.p. > 25f C. NMR (DMSO) δ: 9.2 (IH, s), 8.8 (IH, s), 8.7 (IH, d), 8.4 (IH, d), 8.2 (IH, s), 8.1 (IH, s), 7.95 (2H, d), 7.7 (2H, d), 7.6 (IH, q), 7.4 (IH, s), 4.2 (2H, t), 3.3 (2H, t), 2.5 (3H, s) Example 77 l-[4-Fluoro-3-(3-pyridyl)phenylcarbamoyl]-5-methoxy-6-trifluoromethyl indoline A solution of 4-fluoro-3-(pyrid-3-yl)phenylcarbonyl azide (D59) (270 mg, 1.1 mmol) in toluene (10 ml) was refluxed under argon for 45 minutes and cooled. To a stirred solution of die indoline (Dll) (266 mg, 1.1 eq) in dichloromethane was added die isocyanate solution. The total solution was stirred at room temperature overnight, evaporated to dryness and chromatographed (EtOAc→5% MeOH EtOAc, SiO j ). Concentration of fractions afforded the title compound as a white powder (315 mg, 66%). Melting point = 210°-212°C NMR (250 MHz, δ: 8.73 (d, 2H), 8.60 (dd, IH), 8.10 (s, IH), 7.97 (dd, IH), 7.75 (m, IH), 7.65 (m, IH), 7.54 (m, IH), 7.30 (t, IH), 7.21 (s, IH), 4.15 (t, 2H), 3.83 (s, 3H), 3.27 (t, 2H). Mass spec: m/z = 432 MH * Example 78 l-[3-Fluoro-5-(pyrimidin-5-yl)phenylcarbamoyl]-5-methoxy-6-trifluoromethyI indoline 3-Fluoro-5-(pyrimidin-5-yl)phenylcarbonyl azide (D60) (0.22g, 0.00091 mole) was dissolved in dry toluene (15 ml) and heated under reflux under argon for A hour. After cooling to ambient temperature, 5-methoxy-6-trifluoromethyl indoline (Dll) (0.20g, 0.00091 mole) in dichloromediane (8 ml) was added and d e mixture stirred for 18 h. The dichloromediane was removed in vacuo and d e resulting precipitate filtered and dried in vacuo. This was recrystallised from ethyl acetate/60-80 o petroleum ether to afford die title compound (0.17g, 43%). Η NMR (200 MHz, DOMSO) δ (ppm): 3.30 (2H, t, J=8), 3.87 (3H, s), 4.20 (2H, t, J=8), 7.22 (IH, s), 7.38 (IH, dt, J=3, 9), 7.68 (IH, dt, J=3, 11), 7.79 (IH, s), 8.14 (IH, s), 8.90 (IH, s), 9.12 (2H, s), 9.24 (IH, s). Example 79 l-[4-Chloro-3-(4-methyl-3-pyridyl)phenylcarbamoyl]-5-methoxy-6- trifluoromethylindoline 4-Chloro-3-(4-methyl-3-pyridyl)aniline (D62) was converted to die phenyl carbamate in the usual manner and then treated with 5-methoxy-6-trifluoromethylindoline (Dl l). Purification of the residue obtained by flash chromatography on silica gel gave the titie compound (E79) (0.115g, 49%) m.p. 140-141°C. iH NMR (CDCl,) δ: 2.19 (3H, s), 3.28 (2H, t, J=8Hz), 3.82 (3H, s), 4.15 (2H, t, J=8Hz), 6.81 (IH, s), 7.09 (IH, s), 7.20 (IH, d, J=6Hz), 7.25 (IH, s), 7.40 (IH, d, J=8Hz), 7.52-7.59 (IH, m), 8.20 (IH, s), 8.30 (IH, s), 8.45 (IH, d, J=6Hz). Example 80 l-[2 -Dihydro-7-(pyrid-3-yl)benzofuran-5-ylcarbamoyI]-5-methoxy-6- trifluoromethyl indoline Phenyl N-[2,3-dihydro-7-(pyrid-3-yl)benzofuran-5-yl]carbamate (D65) (0.20g, 0.00060mole) in dry DMF (10 ml) was treated under argon witii 5-methoxy-6- trifluoromethyl indoline (D 11 ) (0.13g, 0.00060 mole) and heated under reflux for 18 hours. The reaction was allowed to cool to ambient temperature and d e solvent was removed in vacuo. The residue was dissolved in dichloromediane, washed widi deionised water and 10% sodium hydroxide solution, dried (Na 2 SO ) and evaporated in vacuo. The resulting brown oil was purified by flash column chromatography on silica gel, eluting with 2% metiianol dichloromediane, followed by recrystallisation from ethyl acetate 60-80° petroleum ether to afford the title compound (0.07g, 26%) as a beige solid. Η NMR (200 MHz, DTJMSO) δ (ppm): 3.12-3.49 (4H, m), 3.85 (3H, s), 4.15 (2H, t, J=8), 4.61 (2H, t, J=10), 7.21 (IH, s), 7.40-7.58 (3H, m), 8.07 (IH, dt, J=l, 7), 8.13 (IH, s), 8.43-8.60 (2H, m), 8.88 (IH, d, J=l). Example 81 5-Methoxy-6-trifluoromethyI-l-[6-(2-methylpyridin-3-yloxy)pyridin-3- ylcarbamoyl]indoline 5-Amino-2-(2-methylpyridin-3-yloxy)pyridine was converted to the title compound according to the method of Example 60 to give a white crystalline solid (71%) m.p. 227-230°C. Η NMR (250 MHz, DMSO) δ: 3.28 (2H, t, J8Hz), 3.85 (3H, s), 4.15 (2H, t, J8Hz), 7.09 (IH, d, J8Hz), 7.21 (IH, s), 7.30 (IH, dd, J8Hz, 5Hz), 7.49 (IH, d, J8Hz), 8.04 (IH, dd, J8Hz, 2Hz), 8.10 (IH, d, J2Hz), 8.32 (IH, d, J5Hz), 8.72 (IH, s). MS(EI) m/e=445 (MIT) Example 82 5-Methoxy-6-trifluoromethyl-l-[6-(4-methylpyridin-3-yloxy)pyridin-3- ylcarbamoyI]indoIine 5-Amino-2-(4-methylpyridin-3-yloxy)pyridine was converted to the title compound according to the method of Example 60 to give a white crystalline solid (51%) m.p. 188-191°C. Η NMR (250 MHz, DMSO) δ: 3.30 (2H, t, J8Hz), 3.83 (3H, s), 4.15 (2H, t, J8Hz), 7.10 (IH, d, J8Hz), 7.20 (IH, s), 7.38 (IH, d, J5Hz), 8.04 (IH, dd, J8Hz, 2Hz), 8.10 (IH, s), 8.17 (IH, d, J2Hz), 8.29 (IH, s), 8.30 (IH, d, J5Hz), 8.72 (IH, s). MS (El) m/e = 445 (MH + ) The following examples were prepared using similar techniques: Pharmacological data [3H]-mesulergine binding to rat or human 5-HT2C clones expressed in 293 cells in vitro Compounds were tested following the procedure outlined in WO 94/04533. The compounds of examples 1 to 165 have pKi values of 5.8 to 9.7. Reversal of MCPP-induced Hypoiocomotion Compounds were tested following the procedure outlined in WO 94/04533. The compound of examples 1, 3, 7, 8, 21, 24, 25, 26, 31, 40, 42, 52, 53, 54, 55, 77, 78, 79, 80 and 81 have I 50' S between 0.5 and 5.5 mg/kg p.o.

Claims: Claims: 1. A compound of formula (I) or a salt thereof: wherein: pi and P 2 are independentiy phenyl, aromatic or partially saturated monocyclic or bicyclic heterocyclic rings containing up to three heteroatoms selected from nitrogen, oxygen or sulphur, A is a bond, a chain of 1 to 5 atoms optionally substituted by . alkyl or A is an optionally substituted phenyl or an optionally substituted 5- to 7-membered heterocyclic ring containing up to three heteroatoms selected from nitrogen, oxygen or sulphur, Ri and R 2 groups are each independentiy hydrogen, Cι_ alkyl optionally substituted by NRi2Rl3 5 C2- alkenyl, C2- alkynyl, Cι_ alkylthio, cyano, nitro, halogen, CF3> C2F5, NR 12 * 13 . CONR 12 Rl 3 , NR 12 CORl 3 , S(O) p NR 12 R 13 , CHO, OCF3, SCF3, CORl 4 , O^OR 14 , CO 2 R 14 or ORI where p is 1 or 2 and R 12 , R i3 and Ri 4 are independentiy hydrogen, C\. alkyl, optionally substituted aryl or optionally substituted arylCι_6alkyl; n and m are independently 0, 1 or 2; R 3 is hydrogen or C\.^ alkyl; R 4 is a group of formula (i): in which: X and Y are both nitrogen, one is nitrogen and die other is carbon or a CR**^ group or one is a CR-5 group and die other is carbon or a CR-5 group; R5, R6, R7 an d R8 groups are independentiy hydrogen, C\. alkyl optionally substituted by one or more fluorine atoms, C2- alkenyl, C3. cycloalkyl, C3.6 cycloalkylCι_6alkoxy, C2-6 alkynyl, C3. cycloalkyloxy, C3. cycloalkyl-Cι_6 alkyl, Cj_ alkylthio, C3. cycloalkylthio, C3.6 cycloalkyl-Cι_6 alkylthio, Cι_6alkoxy, hydroxy, halogen, nitro, OCF3, SCF3, SO2CF3, SO2F, formyl, C2. alkanoyl, cyano, optionally substituted phenyl or tiiienyl, NR 2 R 13 » CONR 12 R 13 or CC^R 14 where where R 12 , R 13 and R 14 are as defined for R 1 ; or R 6 and R 7 form part of an optionally substituted 5- or 6-membered carbocyclic or heterocyclic ring; R and R O are independentiy hydrogen or Cj_ alkyl; or R 4 is a group of formula (ii): (ϋ) in which X and Y are both nitrogen, one is nitrogen and die other is a CR-^ group or X and Y are both CR-5 groups and R-5, R6, R 7 and R* are as defined in formula (I); and Ri i is hydrogen or Cι_ alkyl, or R 4 is a group of formula (iii): (iii) in which R 6 , R 7 , X and Y are as defined in formula (i) and Z is O, S, CH2 or NR 15 where R 15 is hydrogen or C . alkyl. 2. A compound according to claim 1 in which A is a bond or a group CH2O, OCH2. or O. 3. A compound according to claim 1 or 2 in which R 2 is hydrogen, halogen, methyl, CF 3 or OCF 3 . 4. A compound according to any one of claims 1 to 3 in which R 3 is hydrogen. 5 A compound according to any one of claims 1 to 4 in which R 4 is a group of formula (i): in which R6 and R 7 are as defined in formula (i). 6 A compound according to any one of claims 1 to 5 in which R6 is trifluoromethyl or halogen and R 7 is Cι. alkox , C g lley ldiio or Cι_ alkyl. 7. A compound according to claim 1 which is: l-[(3-Pyridyl)-3-phenyl carbamoyl]-5-methoxy-6-trifluoromethyl indoline, l-[(4-Pyridyl)-3-phenyl carbamoyl]-5-methylthio-6-trifluσromethyl indoline, l-[(3-Pyridyl)-3-phenyl carbamoyl]-5-methylthio-6-tiifluoromethyl indoline, l-[(3-Pyridyl)-4-phenyl carbamoyl]-5-methoxy-6-trifluromethylindoline, l-[(4-Pyridyl)-4-phenyl carbamoyl] -5-methoxy-6- trifluoromethyl indoline, l-[(2-Pyridyl)-3-phenyl carbamoyl]-5-methoxy-6-trifluoromethyl indoline, l-[4-Methyl-3-(3-Pyridyl)-phenylcarbamoyl]-5-methoxy-6- trifluoromethyl indoline, l-[3-Fluoro-5-(3-pyridyl)phenylcarbomoyl]-5-methoxy-6-trifluoromethyl indoline, l-[2-Fluoro-5-(3-pyridyl) phenyl carbamoyl]-5-methoxy-6-trifluoromethyl indoline, l-(5-Phenyl pyrid-3-yl carbamoyl)-5-methoxy-6-trifluoromethyl indoline, l-(5-Phenyl pyrid -3-yl carbamoyl)-5-methylthio-6-trifluoromethyl indoline, l-[5-(3-Pyridyl)-pyrid-3-yl carbamoyl]-5-methoxy-6-trifluoromethyl indoline, 1 -[5-(4-Trifluoromethylphenyl)-pyrid-3-yl carbamoyl]-5-methoxy-6-trifluoromethyl indoline, l-[5-(4-Metiιylphenyl)-pyrid-3yl carbamoyl]-5-methoxy-6-trifluoromethyl indoline, l-[5-(2-Thienyl)-pyrid-3-yl carbamoyl]-5-methoxy-6-trifluoromethyl indoline, l-[5-(3-Thienyl)-pyrid-3-yl carbamoyl]-5-methoxy-6-trifluoromethyl indoline, l-[5-(2-Pyrrolyl)-pyrid-3-yl carbamoyl)-5-methoxy-6-trifluoromethyl indoline, l-[5-(4-Pyridyl)-pyrid-3-yl carbamoyl]-5-methoxy-6-trifluoromethyl indoline, l-[2-(3-Pyridyl)-dιiazol-4-yl carbamoyl]-5-methoxy-6-trifluoromethyl indoline, l-[2-(2-Pyridyl)-thien-5-yl carbamoyl]-5-methoxy-6-trifluoromethyl indoline, l-(3-Ruoro-5-(4-methyl-3-pyridyl)phenylcarbamoyl)-5-methoxy-6- trifluoromethylindoline, l-(5-(2,6-Difluorophenyl)-3-pyridylcarbamoyl)-5-methoxy-6- trifluoromethylindoline, 6-Chloro-5-methyl- 1 -(4-methyl-3-(pyrid-3-yl)-phenylcarbamoyl) indoline, l-(4-Methyl-3-(pyrid-3-yl) phenylcarbamoyl)-5-thiomethyl-6- trifluoromethyl indoline, l-(3-Fluoro-5-(pyrid-3-yl)phenylcarbamoyl)-5-thiomethyl-6- trifluoromethyl¬ indoline, l-(4-CWoro-3-(pyrid-3-yl)phenylcarbamoyl)-5-methoxy-6-trifluoromemylindoline, 5-Methoxy- 1 -(5-methyl-( 1 ,2-4-oxadiazol-3-yl)-phenylcarbamoyl)-6-trifluorometiιyl indoline, l-[4-Medιyl-3-(4-methyl-3-pyridyl)phenylcarbamoyl]-5-methoxy-6- trifluoromethyl indoline, l-[5-Bromo-3-(pyrid-3-yl)phenylcarbamoyl]-5-methoxy-6- trifluoromethylindoline, l-[4-t-Butyl-3-(pyrid-3-yl)phenylcarbamoyl]-5-methoxy-6- trifluoromethylindoline, l-[4-Medioxy-3-(pyrid-3-yl)phenylcarbamoyl]-5-me oxy-6-trifluoromethylindoline, l-[5-Fluoro-4-methoxy-3-(pyrid-3-yl)phenylcarb__moyl]-5-methoxy-6- trifluoromethylindoline, l-[3-Bromo-4-methyl-5-(3-pyridyl)phenylcarbamoyl]-5-methoxy-6- trifluoromethylindoline, l-[3-(4-Isoquinolyl)phenylcarbamoyl]-5-methoxy-6-trifluoromethyl indoline, 1 -[5-(4-Metiιyl-3-pyridyl)-pyrid-3-ylcaιbamoyl] -5-methoxy-6- trifluoromethylindoline, 1 - [6- (3-Pyridyl)-pyrid-3-ylcarbamoyl] -5-methoxy-6- trifluoromethylindoline, 1 -[5-(2-Furyl)-pyrid-3-ylcarbamoyl-5-methoxy-6-trifluoromethyl indoline, l-[2-(Pyrazinyl)-thiazol-4-ylcarbamoyl]-5-methoxy-6-trifluoromethyl-indoline, l-[3-(5-Pyrimidyl)phenylcarb--moyl]-5-methoxy-6- trifluoromethyl-indoline, 1 - [3-(4-Methy l-3-pyridyl)phenylcarbamoyl] -5-methoxy-6- trifluoromethylindoline, 1 - [5-Ethyl-3-φyrid-3-yl)phenylcarbamoyl]-5-methoxy-6-trifluoromethylindoline, 5-Methoxy-l-[5-phenyl-3-(pyrid-3-yl)phenylcarbamoyl]-6- trifluoromethyl indoline, 6-Chloro-5-methyl-l-[4-methyl-3-(4-methyl-3-pyridyl)phenyl carbamoyl] indoline, l-[3-(pyrid-3-ylammocarbonyl)-phenylcarbamoyl]-5-methoxy-6-trifluoromethyl- indoline, l-[3-(Pyrid-3-ylaminocarbonyl)-phenylcarbamoyl]-5-methylthio-6- trifluoromethyl¬ indoline, l-[3-(Pyrid-4-ylaminocarbonyl)-phenylcarbamoyl]-5-methyldιio-6-trifluoromethyl indoline, l-[4-(Pyrid-3-ylaminocarbonyl)-phenylcarbamoyl]-5-methylthio- 6- trifluoromethyl indoline, l-[4-(Pyrid-4-ylaminocarbonyl)-phenylcarbamoyl]-5-methylthio-6- trifluoromethyl indoline, l-[3-(3-pyridylcarbonyl)phenylcarbamoyl]-5-methoxy-6- trifluoromethyl indoline, l-[3-(Pyrid-3-yl-aminosulphonyl)-phenylcarbamoyl]5-methoxy-6- trifluoromethyl¬ indoline, 5-Methylthio-6-trifluoromethyl- 1 -[6-(pyridin-3-yloxy)pyridin-3- ylcarbamoyl)]indoline, 5-Methoxy-6-πifluoromethyl- 1 - [6-(pyridin-3-yloxy)pyridin-3-ylcarbamoyl]indoline, 5-Methoxy-6-trifluoromethyl- 1 -[4-(pyridin-4-ylmethyloxy)phenyl carbamoyl] indoline, 5-Methoxy-6-trifluoromethyl-l-[6-(pyridin-4-ylmethyloxy)pyridin-3- ylcarbamoyl]indoline, 5-Methylthio-6-trifluoromethyl- 1 -[4-(pyrid-4-yl-methylamino carbonyl)phenyl carbamoyl] indoline, Trans-5-Medιylthio-6-trifluoromethyl-l-{4-[2-ethenyl-(4-pyridyl)]-phenyl carbamoyl } -indoline, 5-Methylthio-6-trifluoromethyl- 1 - { 4-[2-ethyl(4-pyridyl)]phenyl carbamoyl } indoline, 1 -( 1 -(4-Pyridyl)-5-indolylcarbamoyl)-5-methoxy-6-trifluoromethylindoline, 5-Methoxy-6-trifluoromethyl- 1 - [4-(pyridin-4-ylthiomethyl)phenyl carbamoyl]indoline, 5-Methoxy-6-trifluoromethyl- 1 -[4-(pyridin-4-ylsulphonylmethyl) phenylcarbamoyl]indoline, 5-Methoxy-6-trifluoromethyl- 1 - [4-(pyridin-4-ylmetiιylthio)phenyl carbamoyl]indoline, 5-Methyltiιio-6-trifluoromethyl-l-[(6-phenoxy)-3-pyridylcarbamoyl]-indoline, 5-Methoxy-6-trifluoromethyl-l-[2-(pyridin-3-yloxy)pyridin-4-ylcarbamoyl)]indoline, 5-Methyltiιio-6-trifluoromethyl- l-[6-(2-methylpyridin-3-yloxy) pyridin-3- ylcarbamoyl]indoline, 5-Methyldtio-6-trifluoromethyl-l-[6-(6-methylpyridin-3-yloxy)pyridin-3- ylcarbamoyl]indoline, 5-Methoxy-6-trifluoromethyl- 1 -[6-(pyridin-3-yldιio)pyridin-3-ylcarbamoyl]indoline, 5-Methylthio-6-trifluoromethyl- l-[4-(pyrid-3-ylmethyl)amido phenyl carbamoyl]indoline, 5-Methylthio-6-trifluoromethyl- l-[3-(pyrid-4-ylmethyl) amidophenylcarbamoyl] indoline, 5-Metiιylthio-6-trifluoromethyl- 1 -[4-(pyrid-2-ylmetiιyl) amidophenylcarbamoyl] indoline, l-(l-(3-Pyridylmemyl)-5-indolylcarbamoyl)-5-methoxy-6-tr__fluoromethylindoline, 1 -( 1 -(4-Pyridylmetiiyl)-5-indolylcarbamoyl)-5-methoxy-6-trifluoromethylindoline, l-(l-(3-pyridyl)-5-indolylcarbamoyl)-5-methoxy-6-trifluoromethyl indoline, 5-Methyldιio-6-trifluoromethyl- 1- { 3-[2-(3-pyridyl)thiazol-4-yl]phenylcarbamoyl } indoline, 5-Medιylthio-6-trifluoromedιyl- 1 - { 4-[2-(4-pyridyl)-tiιiazol-4-yl]phenyl carbamoyl } indoline, 5-Medιylthio-6-trifluoromethyl- 1- { 4-[2-(3-pyridyl)-tiιiazol-4- yl]phenylcarbamoyl ) indoline, l-[4-Fluoro-3-(3-pyridyl)phenylcarbamoyl]-5-methoxy-6-trifluoromethyl indoline, 1 - [3-Huoro-5-(pyrimidin-5-yl)phenylcarbamoyl]-5-methoxy-6-trifluoromethyl indoline, l-[4-Chloro-3-(4-medιyl-3-pyridyl)phenylcarbamoyl]-5-methoxy-6- trifluoromethylindoline, l-[2,3-Dihydro-7-(pyrid-3-yl)benzofuran-5-ylca bamoyl]-5-methoxy-6- trifluoromethyl indoline, 5-Methoxy-6-trifluoromethyl- 1 -[6-(2-methylpyridin-3-yloxy)pyridin-3- ylcarbamoyl]indoline, 5-Methoxy-6-trifluoromethyl-l-[6-(4-methylpyridin-3-yloxy)pyridin-3- ylcarbamoyl]indoline, and pharmaceutically acceptable salts thereof. 8. A compound according to any one of claims 1 to 7 for use in therapy. 9. A pharmaceutical composition which comprises a compound according to any one of claims 1 to 7 and a pharmaceutically acceptable carrier or excipient. 10. A process for the preparation of a compound of formula (I) or a pharmaceutically acceptable salt thereof, which process comprises: (a) the coupling of a compound of formula (ϋ); (II) with a compound of formula (HI); D-R 4 ' (HI) wherein A, pi and P 2 are as defined in formula (I) , C and D contain the appropriate functional group(s) necessary to form the moiety -NR 3 CO when coupled, die variables R 1 ', R 2 ', R 3 and R 4' are R 1 , R 2 , R 3 and R 4 respectively, as defined in formula (I), or groups convertible thereto, and thereafter optionally and as necessary and in any appropriate order, converting any Ri , R 2' , R 3 and R 4 , when other than Ri, R 2 , R 3 and R 4 respectively to R 1 , R 2 , R 3 and R 4 , intercon verting R 1 , R 2 , R 3 and R 4 and forming a pharmaceutically acceptable salt thereof; or (b) the coupling of a compound of formula (TV); (TV) with a compound of formula (V); (V) wherein pi, P 2 , Ri', R 2 ', R 3 ' and R 4 ' are as defined above and E and G contain the appropriate functional group(s) necessary to form the A moiety when coupled and thereafter optionally and as necessary and in any appropriate order, converting any R 1 ', R 2' , R 3' and R 4 ', when other than R 1 , R 2 , R 3 and R 4 respectively to R 1 , R 2 , R 3 and R 4 , intercon verting Ri, R 2 , R 3 and R 4 and forming a pharmaceutically acceptable salt.

Inventors: DAVIES DAVID THOMAS, DUCKWORTH DAVID MALCOM, FORBES IAN THOMSON, GASTER LARAMIE MARY, JONES GRAHAM ELGIN, MULHOLLAND KEITH RAYMOND, WYMAN PAUL ADRIAN, DAVIES, DAVID, THOMAS, DUCKWORTH, DAVID, MALCOM, FORBES, IAN, THOMSON, GASTER, LARAMIE, MARY, JONES, GRAHAM, ELGIN, MULHOLLAND, KEITH, RAYMOND, WYMAN, PAUL, ADRIAN
Applicants: DAVIES DAVID THOMAS, DUCKWORTH DAVID MALCOM, FORBES IAN THOMSON, GASTER LARAMIE MARY, JONES GRAHAM ELGIN, MULHOLLAND KEITH RAYMOND, SMITHKLINE BEECHAM PLC, WYMAN PAUL ADRIAN, DAVIES, DAVID, THOMAS, DUCKWORTH, DAVID, MALCOM, FORBES, IAN, THOMSON, GASTER, LARAMIE, MARY, JONES, GRAHAM, ELGIN, MULHOLLAND, KEITH, RAYMOND, WYMAN, PAUL, ADRIAN
Application year: 1996
Main classification: C07D401
IPC codes: A61K31, A61P25, A61P43, C07D401, C07D403, C07D405, C07D409, C07D413, C07D417