2-Arylpyrazolisoquinoline and cinnolinone derivatives are known in the art to exhibit anti- allergic and anti-inflammatory activity. A series of structurally distinct triazole compounds have now surprisingly been found to be useful for the modulation of inflammatory conditions. In a first aspect the present invention therefore provides a compound of formula (I): wherein: each group Rl independently represents a halogen atom or a C1-C6 alkyl, C1-C6 alkoxy, C3-C7 cycloalkyl, hydroxyl, nitro, cyano, C02R2, NR3R4, CONR3R4, So2NR3R4 or NR3So2R4 group; each group R2, R3 and R4 independently represents a hydrogen atom or a C1-C6 alkyl or C3-C7 cycloalkyl group; nisO, 1,2,30r4; A is CH2, X=Y, Y=X, X'-Y' or Y'-X'; X is N or CR5 where R5 represents a hydrogen or halogen atom, or a nitro, carboxyl, sulphonic acid (SO2H), CI-C6 alkyl, C3-C7 cycloalkyl, C1-C6 alkoxy, Cl-C6 alkoxycarbonyl, C3-C7 cycloalkoxycarbonyl, C1-C6 alkylsulphonyl, C3-C7 cycloalkylsulphonyl, NR7R8, CONR7R8 or SO2NR7R8 group where R7 and R8 each independently represent a hydrogen atom, a C3-C7 cycloalkyl group, an optionally substituted phenyl-, pyridinyl- or imidazolyl-sulphonyl group, or an optionally substituted C1-C6 alkyl(sulphonyl) group, or together with the nitrogen atom to which they are attached

form an optionally substituted 3- to 7-membered heterocyclic ring optionally containing a further heteroatom selected from nitrogen, oxygen or sulphur; Y is N or CR6 where R6 represents a hydrogen or halogen atom, or aNR7R8, C1-C6 alkoxy, C3-C7 cycloalkyl or an optionally substituted C1-C6 alkyl group where R7 and R8 are as hereinbefore defined; X' is C=O, SO2, NR9 or CHAR'0 where R9 represents a hydrogen atom, or a C3-C7 cycloalkyl or an optionally substituted C1-C6 alkyl group, and R10 represents a hydrogen atom or a C1-C6 alkyl, C3-C7 cycloalkyl or NR7R8 group where R7 and R8 are as hereinbefore defined; Y' is CHR10 where R10 is as hereinbefore defined, or, when X' is NR9 or CHR10, Y may additionally represent C=O or SO2; and Arl represents a phenyl, pyridinyl, pyrimidinyl, benzothiazolyl, quinolyl or quinoxalinyl group, each of which may be optionally substituted; or a pharmaceutically acceptable salt or solvate thereof.

In the present specification, unless otherwise indicated, an alkyl group, whether alone or part of another group, can be straight or branched chain and a 'heterocyclic ring' is saturated.

Each group Rl independently represents a halogen atom (e.g. fluorine, chlorine or bromine) or a C1-C6, preferably C1-C4, more preferably C1-C2, alkyl, C1-C6, preferably C1 -C4, more preferably C1-C2, alkoxy, C3-C7, preferably C4-C6, cycloalkyl, hydroxyl, nitro, cyano, C02R2, NR3R4, CONR3R4, S02NR3R4 or NR3S02R4 group.

Preferred R' groups include halogen atoms, in particular fluorine atoms.

Each group R2, R3 and R4 independently represents a hydrogen atom or a C1 -C6 alkyl or C3-C7 cycloalkyl group. Preferably, each group R2, R3 and R4 independently represents a hydrogen atom or a C1-C3 alkyl or C3-C6 cycloalkyl group.

Preferably n is 0, 1 or 2. Particularly advantageous compounds of formula (I) are those in which n is 0.

The group A is CH2, X=Y, Y=X, X'-Y' or Y'-X'. Particularly advantageous compounds of formula (I) are those in which A is X=Y or X'-Y' such that X or X' is attached directly to the phenyl ring and Y or Y' is attached to the triazole ring.

The group X is N or CR5 where R5 represents a hydrogen or halogen atom (e.g. fluorine, chlorine or bromine), or a nitro, carboxyl, sulphonic acid, C1-C6, preferably C1-C4, alkyl, C3-C7 cycloalkyl, C1-C6, preferably C1-C4, alkoxy, C1-C6 alkoxycarbonyl, preferably C1-C4 alkoxycarbonyl, C3-C7 cycloalkoxycarbonyl, C1-C6 alkylsulphonyl, preferably C1-C4 alkylsulphonyl, C3-C7 cycloalkylsulphonyl, NR7R8, CONR7R8 or SO2NR7R8 group where R7 and R8 each independently represent a hydrogen atom, a C3-C7 cycloalkyl group, an optionally substituted (e.g. C1-C6 alkyl substituted) phenyl-, pyridinyl- or imidazolyl-sulphonyl group, or an optionally substituted C1-C6 alkyl(sulphonyl) group, or together with the nitrogen atom to which they are attached form an optionally substituted (e.g. C1-C6 alkyl substituted) 3- to 7-membered heterocyclic ring optionally containing a further heteroatom selected from nitrogen, oxygen or sulphur.

Preferably X represents N or CR5 where R5 represents a hydrogen or halogen atom, or a nitro, C1-C6 alkyl, C1-C6 alkoxy, NR7R8 or SO2NR7R8 group where R7 and R8 each independently represent a hydrogen atom, an optionally substituted imidazolylsulphonyl group or an optionally substituted C1 -C6 alkyl(sulphonyl) group, or together with the nitrogen atom to which they are attached form an optionally substituted 3- to 7-membered heterocyclic ring optionally containing a further heteroatom selected from nitrogen and oxygen.

Most preferably, X represents N or CR5 where R5 represents a hydrogen, chlorine or bromine atom, or a nitro, C1-C3 alkyl (especially isopropyl), C1-C3 alkoxy (especially methoxy), NR7R8 or So2NR7R8 group where R7 and R8 each independently represent a hydrogen atom, a methyl-substituted imidazolylsulphonyl group, or an optionally substituted C1-C3 alkyl(sulphonyl) group, or together with the nitrogen atom to which they are attached form a 4- to 6-membered heterocyclic ring optionally containing a further heteroatom selected from nitrogen and oxygen (e.g. an azetidine, morpholine, piperidine, pyrrolidine or piperazine ring).

When R7 or R8 represents an optionally substituted alkyl or alkylsulphonyl group, examples of the one or more (e.g. 1, 2 or 3) optional substituents that may be present in the alkyl moiety include hydroxyl, amino and C1-C6 alkoxy (particularly methoxy) groups.

The group Y is N or CR6 where R6 represents a hydrogen or halogen (e.g. fluorine, chlorine or bromine) atom, or a NR7R8, C-C6, preferably C1-C4, alkoxy, C3-C7 cycloalkyl or an optionally substituted C1-C6 , preferably C1-C4, alkyl group where R7 and R8 are as previously defined.

Preferably Y is N or CR6 where R6 represents a hydrogen atom, a NR7R8 group where R7 and R8 are as previously defined (particularly an azetidine or morpholine ring) or an optionally substituted C1-C4 alkyl (e.g. methyl, ethyl, propyl, isopropyl or butyl) group.

When R6 represents an optionally substituted alkyl group, the one or more (e.g. 1, 2 or 3) optional substituents may be selected from the group including halogen atoms (e.g. fluorine, chlorine or bromine) and NR'R' where each R' independently represents a hydrogen atom, or a C1-C6 alkyl or C3-C7 cycloalkyl group, or the groups R' may together with the nitrogen atom to which they are attached form a 3- to 7-membered heterocyclic ring optionally containing a further heteroatom selected from nitrogen, oxygen or sulphur (e.g. morpholinyl or piperazinyl), or the groups R' may together with the nitrogen atom to which they are attached from an imidazole, pyrazole or pyrrole ring optionally substituted

by one or more (e.g. one or two) substituents selected from C1 -C6 alkyl and C3-C7 cycloalkyl groups.

The group X' represents C=O, SO2, NR9 or CHAR10 where R9 represents a hydrogen atom, or a C3-C7 cycloalkyl or an optionally substituted C1 -C6, preferably C1-C4, alkyl group (e.g. methyl, ethyl, propyl or isopropyl), and RIO represents a hydrogen atom or a C1-C6, preferably C1-C4, alkyl (e.g. methyl, ethyl, propyl or isopropyl), Q-C7 cycloalkyl or NR7R8 group where R7 and R8 are as previously defined.

When R9 represents an optionally substituted alkyl group, examples of the one or more (e.g. 1, 2 or 3) optional substituents that may be present in the alkyl group include halogen atoms (e.g. fluorine, chlorine or bromine), C1-C6 alkoxy and NR"R" where each R" independently represents a hydrogen atom, or a C1-C6 alkyl or C3-C7 cycloalkyl group, or the groups R" may together with the nitrogen atom to which they are attached form a 3- to 7-membered heterocyclic ring optionally containing a further heteroatom selected from nitrogen, oxygen or sulphur (e.g. morpholinyl or piperazinyl). Specific examples of optionally substituted alkyl groups include methyl, ethyl, propyl, isopropyl, 2-aminoethyl and 2,2,2-trifluoroethyl.

Preferably X' represents C=O, NR9 or CHR10 where R9 represents a hydrogen atom or an optionally substituted C1-C4 alkyl group, and Rl° represents a hydrogen atom.

The group Y' represents CHR10 where Rl° is as hereinbefore defined, or, when X' is NR9 or CHR10, Y' may additionally represent C=O or SO2. Preferably when Y' represents CHR10, R10 represents a hydrogen atom or a C1-C4 alkyl, especially methyl, group.

The group Arl represents a phenyl, pyridinyl, pyrimidinyl, benzothiazolyl (e.g. 2-benzothiazolyl), quinolyl (e.g. 2-, 3- or 6-quinolyl) or quinoxalinyl (e.g.

2-quinoxalinyl) group, each of which may be optionally substituted, e.g. by one or more, preferably one to four, more preferably one or two, substituents selected from halogen

atoms (e.g. fluorine, chlorine or bromine) or amino, hydroxyl, C1-C6 alkoxycarbonyl - (preferably C1-C4 alkoxycarbonyl), C3-C7 cycloalkyl (preferably cycbhexyl), C1-C6 alkylthio (preferably C1-C4 alkylthio, e.g. methyl- or ethylthio), C1-C6 alkyl (preferably C1-C4 alkyl, e.g. methyl, ethyl, propyl, isopropyl or butyl), alkyloxyalkyl containing up to 6 carbon atoms and C1-C6 alkoxy (preferably C1-C4 alkoxy, e.g. methoxy or ethoxy) groups, which latter four groups may, in turn, be optionally substituted by one or more, e.g. one, two, three, four, five or six, substituents selected from halogen atoms (e.g. fluorine, chlorine or bromine), hydroxyl and amino groups, e.g. trifluoromethyl, trifluoromethylthio or trifluoromethoxy.

Preferably Arl represents a phenyl, pyridinyl, 3-quinolyl or 6-quinolyl group, each of which may be optionally substituted by one or more substituents selected from halogen atoms, C3-C7 cycloalkyl, C1 -C6 alkylthio, C1-C6 alkyl, C1-C6 alkoxy, trifluoromethyl, trifluoromethylthio and trifluoromethoxy.

Particularly preferred compounds of the invention include: 2-(4-Chlorophenyl)-2,4-dihydro-3-hydroxy-[1,2,3]triazolo[1,5 -a]indolinium hydroxide, inner salt, 2,4-Dihydro-3-hydroxy-2-[4-(trifluoromethyl)phenyl]-[ 1 ,2,3]triazolo[ 1 ,5-a]indolinium hydroxide, inner salt, 4,5-Dihydro-3-hydroxy-2- [4-(trifluoromethyl)phenyl]- [1 ,2,3]triazolo[ 1 ,5-a quinolinium hydroxide, inner salt, 2-(4-Chlorophenyl)-4,5-dihydro-3-hydroxy 1 ,2,3]triazolo [1 ,5-a]quinolinium hydroxide, inner salt, 2-(4-Chloro-2-methylphenyl)-4,5-dihydro-3-hydroxyS 1 ,2,3]triazolo[ 1 ,5-a]quinolinium hydroxide, inner salt, 4,5-Dihydro-3-hydroxy-5-oxo-2-[4-(trifluoromethyl)phenyl]-[1 ,2,3]triazolo[1,5-a]- quinazolinium hydroxide, inner salt, 5-Chloro-3-hydroxy-2- [4-(trifluoromethyl)phenyl]-[ 1 ,2,3]triazolo [1 ,5-a]quinazolinium hydroxide, inner salt,

3-Hydroxy-2-[4-(trifluoromethyl)phenyl]-[1,2,3]triazolo[1,5- a]quinazolinium hydroxide, inner salt, 3-Hydroxy-2-[4-(trifluoromethyl)phenyl]-[ 1 ,2,3]triazolo[ 1 ,5-a]quinolinium hydroxide, inner salt, 3-Hydroxy-5-( 1 -methylethyl)-2-[4-(trifluoromethyl)phenyl]-[ 1 ,2,3]triazolo[ 1 ,5-a quinazolinium hydroxide, inner salt, 4,5-Dihydro-9-fluoro-3-hydroxy-2-[4-(trifluoromethyl)phenyl] -[1,2,3]triazolo[1,5-a]- quinolinium hydroxide, inner salt, 9-Fluoro-3-hydroxy-2-[4-(trifluoromethyl)phenyl]-[1,2,3]tria zolo[1,5-a]quinolinium hydroxide, inner salt, 4,5-Dihydro-3-hydroxy-5-oxo-4-methyl-2-[4-(trifluoromethyl)p henyl]- [1,2,3]triazolo[1,5-a]quinazolinium hydroxide, inner salt, 6,9-Difluoro-4,5-dihydro-3-hydroxy-2-[4-(trifluoromethyl)phe nyl]-[1,2,3]triazolo[1,5- a]quinolinium hydroxide, inner salt, 4,5-Dihydro-9-fluoro-3-hydroxy-2-(3-pyridinyl)-[1,2,3]triazo b[1,5-a]quinolinium hydroxide, inner salt, 2-(6-Chloro-3-pyridinyl)-9-fluoro-4,5-dihydro-3-hydroxy-[1,2 ,3]triazolo[1,5-a]- quinolinium hydroxide, inner salt, 6,9-Difluoro-3-hydroxy-2-[4-(trifluoromethyl)phenyl]-[ 1 ,2,3]triazolo[1 ,5-aF quinolinium, hydroxide, inner salt, 4,5-Dihydro-3-hydroxy-4-methyl-2-[4-(trifluoromethyl)phenyl] -[1,2,3]triazolo[1,5-a]- quinolinium hydroxide, inner salt, 3-Hydroxy-4-methyl-2-[4-(trifluoromethyl)phenyl]-[1,2,3]tria zolo[1,5-a]quinolinium hydroxide, inner salt, 2-(6-Chloro-3-pyridinyl)-9-fluoro-3-hydroxy-[ 1 ,2,3]triazolo[ 1 ,5-a]quinolinium hydroxide, inner salt, 9-Fluoro-3-hydroxy-2-(3-pyridinyl)- 1 ,2,3]triazolot 1 ,5-a]quinolinium hydroxide, inner salt, 4,5-Dihydro-3-hydroxy-5-oxo-2-[4-(trifluoromethoxy)phenyl]-[ 1,2,3]triazolo[1,5-a]- quinazolinium hydroxide, inner salt,

4,5-Dihydro-9-fluoro-3-hydroxy-4-methyl-2-[4-(trifluoromethy l)phenyl]- [1 ,2,3]triazolo[ 1 ,5-a]quinolinium hydroxide, inner salt, 4,5-Dihydro-3-hydroxy-5-oxo-2- [4-(trifluoromethyl)phenyl]-4-(2,2,2-trifluoroethyl) [l ,2,3]triazolo[ 1 ,5-a]quinazolinium hydroxide, inner salt, 4,5-Dihydro-3-hydroxy-5-oxo-4-methyl-2- [4-(trifluoromethoxy)phenyl]- [1 ,2,3]triazolo[ 1 ,5-a]quinazolinium hydroxide, inner salt, 2-(6-Chloro-3-pyridinyl)-4,5-dihydro-9-fluoro-3-hydroxy-4-me thyl-[1,2,3]triazolo[1,5- a]quinolinium hydroxide, inner salt, 2-(6-Chloro-3-pyridinyl)-9-fluoro-3-hydroxy-4-methyl-[1,2,3] triazolo[1,5-a]- quinolinium hydroxide, inner salt, 9-Fluoro-3-hydroxy-4-methyl-2-[4-(trifluoromethyl)phenyl]- [ 1 ,2,3]triazolo [1 ,5-a quinolinium hydroxide, inner salt, 4,5-Dihydro-2-(4-fluorophenyl)-3-hydroxy-[ 1 ,2,3]triazolo[ 1 ,5-a]quinolinium hydroxide, inner salt, 5 -B romo-3 -hydroxy-2- [4-(trifluoromethyl)phenyl ] 1 1 ,2,3]triazolo[ 1 ,5-a]quinolinium hydroxide, inner salt, 4,5-Dihydro-3-hydroxy-2-(4-methylphenyl)-[1,2,3]triazolo[1,5 -a]quinolinium hydroxide, inner salt, 5-Bromo-9-fluoro-3-hydroxy-2-[4-(trifluoromethyl)phenyl]-[1, 2,3]triazolo[1,5-a]- quinolinium hydroxide, inner salt, 2-(4-Fluorophenyl)-3-hydroxy-[1,2,3]triazolo[1,5-a]quinolini um hydroxide, inner salt, 3-Hydroxy-2-(4-methyIphenyl)-C 1,2,3]triazolo[l ,5-a]quinolinium hydroxide, inner salt, 4,5-Dihydro-3-hydroxy-2-[4-(trifluoromethoxy)phenyl]-[1,2,3] triazolo[1,5-a]- quinolinium hydroxide, inner salt, 4,5-Dihydro-3-hydroxy-2-phenyl- [ 1 ,2,3]triazolo[ 1 ,5-a]quinolinium hydroxide, inner salt, 3-Hydroxy-2-[4-(trifluoromethoxy)phenyl)-[1,2,3]triazolo[1,5 -a]quinolinium hydroxide, inner salt, 5-Bromo-2-(4-fluorophenyl)-3-hydroxy-[1,2,3]triazolo[1,5-a]q uinolinium hydroxide, inner salt,

3-Hydroxy-2.phenyl-[ 1 ,2,3]triazolo [1 ,5-a]quinolinium hydroxide, inner salt, 5-Bromo-3-hydroxy-2-phenyl4 1 ,2,3]triazolo [1 ,5-a]quinolinium hydroxide, inner salt, 5 -B romo-3 -hydroxy-2- [4-(trifluoromethoxy)phenyl] 1 ,2,3]triazolo[ 1 ,5-a]quinolinium hydroxide, inner salt, 2-(6-Chloro-3-pyridinyl)-4,5-dihydro-3-hydroxy-[1,2,3]triazo lo[1,5-a]quinolinium hydroxide, inner salt, 3-Hydroxy-5-(4-morpholinyl)-2-[4-(trifluoromethyl)phenyl]-[1 ,2,3]triazolo[1,5-a]- quinolinium hydroxide, inner salt, 3-Hydroxy-5-(4-morpholinyl)-2-[4-(trifluoromethoxy)phenyl]-[ 1,2,3]triazolo[1,5-a]- quinolinium hydroxide, inner salt, 2-(6-Chloro-3-pyridinyl)-3-hydroxy-[ I ,2,3]triazolo[ I ,5-a]quinolinium hydroxide, inner salt, 2-(4-Chlorophenyl)-3-hydroxy-[1,2,3]triazolo[1,5-a]quinolini um hydroxide, inner salt, 5-Bromo-2-(4-chlorophenyl)-3-hydroxy-C 1 ,2,3]triazolot 1 ,5-a]quinolinium hydroxide, inner salt, 3-Hydroxy-4-oxo-2-[4-(trifluoromethyl)phenyl]-4,5-dihydro-[1 ,2,3]triazolo[1,5-a]- quinoxalinium hydroxide, inner salt, 3-Hydroxy-2-[4-(trifluoromethyl)phenyl]-[ ,2,3]triazolo[ 1 ,5-a]quinoxalinium hydroxide, inner salt, 4-Azetidinyl-3-hydroxy-2- [4-(trifluoromethyl)phenyl] - [1,2,3 ]triazolo-[ [1 ,5-a quinoxalinium hydroxide, inner salt, 3-Hydroxy-4-methyl-5-nitro-2-[4-(trifluoromethyl)phenyl]-[1, 2,3]triazolo[1,5-a]- quinolinium hydroxide, inner salt, 2-(4-Chlorophenyl)-3-hydroxy-4-methyl-5-nitro-[1,2,3]triazol o[1,5-a]quinolinium hydroxide, inner salt, 3-Hydroxy-4-(1-methylethyl)-2-[4-(trifluoromethyl)phenyl]-[1 ,2,3]triazolo[1,5-a]- quinoxalinium hydroxide, inner salt, 3-Hydroxy-4-methyl-2-[4-(trifluoromethyl)phenyl]-[1,2,3]tria zolo[1,5-a]- quinoxalinium hydroxide, inner salt,

2-(4-Chlorophenyl)-3-hydroxy-4-oxo-4,5-dihydro-[1,2,3]triazo lo[1,5-a]quinoxalinium hydroxide, inner salt, 2-(4-Chlorophenyl)-3-hydroxy-4-( 1 -methylethyl)-[ 1 ,2,3]triazolo[ 1 ,5-a3quinoxalinium hydroxide, inner salt, 2-(4-Chlorophenyl)-3-hydroxy-4-methyl-[ 1 ,2,3]triazolo[ 1 ,5-a3quinoxalinium hydroxide, inner salt, 3-Hydroxy-5-methyl-4-oxo-2-[4-(trifluoromethyl)phenyl]-4,5-d ihydro-[1,2,3]- triazolo[ 1 ,5-a]quinoxalinium hydroxide, inner salt, 2-(4-Fluorophenyl)-3-hydroxy-5-nitro-[1,2,3]triazolo[1,5-a]q uinolinium hydroxide, inner salt, 5-Amino-2-(4-fluorophenyl)-3-hydroxy-[ 1,2,3 ]triazolo [1,5-a] quinolinium hydroxide, inner salt, 5-Amino-3-hydroxy-4-methyl-2-[4-(trifluoromethyl)phenyl]-[1, 2,3]triazolo[1,5-a]- quinolinium hydroxide, inner salt, 4-Ethyl-3-hydroxy-2-[4-(trifluoromethyl)phenyl]-[1,2,3]triaz olo[1,5-a]quinoxalinium hydroxide, inner salt, 3-Hydroxy-4-methyl-2-(3-pyridinyl)-[1 2,3]triazolo[1,5-a] quinoxalinium hydroxide, inner salt, 2-(3,4-Difluorophenyl)-3-hydroxy-4-methyl-[ 1 ,2,3]triazolo[ [1 ,5-a]quinoxalinium hydroxide, inner salt, 3-Hydroxy-4-methyl-2-(6-methyl-3-pyridinyl)-[1,2,3]triazolo[ 1,5-a]quinoxalinium hydroxide, inner salt, 9-Fluoro-4,5-dihydro-3-hydroxy-2-(6-methyl-3-pyridinyl)-[1,2 ,3]triazolo[1,5-a]- quinolinium hydroxide, inner salt, 9-Fluoro-3-hydroxy-2-(6-methyl-3-pyridinyl)-[ 1 ,2,3]triazolot 1 ,5-a3quinolinium hydroxide, inner salt, 9-Fluoro-4,5-dihydro-3-hydroxy-4-methyl-2-(6-methyl-3-pyridi nyl)- [1 ,2,3]triazolo[ 1 ,5-a]quinolinium hydroxide, inner salt, 9-Fluoro-3-hydroxy-4-methyl-2-(6-methyl-3-pyridinyl)-[1,2,3] triazolo[1,5-a]- quinolinium hydroxide, inner salt.

4,5-Dihydro-3-hydroxy-2-(3-trifluoromethylphenyl)-[ 1 ,2,3]triazolo[ 1 ,5-ahuinolinium hydroxide, inner salt, 3-Hydroxy-2-(3-trifluoromethylphenyl)-[1 ,2,3]triazolo[ 1 ,5-a]quinolinium hydroxide, inner salt, 2-(4-Fluorophenyl)-3-hydroxy-4-methyl-[ 1 ,2,3]triazolo[ 1 ,5-a]quinolinium hydroxide, inner salt, 3-Hydroxy-5-nitro-2-(3-trifluoromethylphenyl)-[1,2,3]triazol o[1,5-a]quinolinium hydroxide, inner salt, 5-Bromo-3-hydroxy-2-(3-trifluoromethylphenyl)-[1,2,3]triazol o[1,5-a]quinolinium hydroxide, inner salt, 5-(1 -Azetidinyl)-3-hydroxy-2-(3-trifluoromethylphenyl)-[ 1 ,2,3]triazolo[ 1,5- a]quinolinium hydroxide, inner salt, 2-(3-Fluorophenyl)-4,5-dihydro-3-hydroxy-4-oxo-[1,2,3]triazo lo[1,5-a]quinoxalinium hydroxide, inner salt, 2-(3-Fluorophenyl)-3-hydroxy-5-nitro-[1,2,3]triazolo[1,5-a]q uinolinium hydroxide, inner salt, 3-Hydroxy-4-methyl-2-(6-methyl-3-pyridinyl)-[1,2,3]triazolo[ 1,5-a]quinolinium hydroxide, inner salt, 3 -Hydroxy-4-methyl-2-(6-methyl-3-pyridiny -nitro- [1,2,3] triazolo[1 ,5- a]quinolinium hydroxide, inner salt, 3-Hydroxy-2-(6-methyl-3-pyridinyl)-5-nitro-[1,2,3]triazolo[1 ,5-a]quinolinium hydroxide, inner salt, 2-(3-Fluorophenyl)-4,5-dihydro-3-hydroxy-5-methyl-4-oxo-[ 1 ,2,3]triazolo[ 1 ,5-a quinoxalinium hydroxide, inner salt, 2-(3-Fluorophenyl)-3-hydroxy-4-( 1-methylethyl)-[1 ,2,3]triazolo[ 1 ,5-a]quinoxalinium hydroxide, inner salt, 2-(3-Fluorophenyl)-3-hydroxy-4-methyl-[1,2,3]triazolo[1,5-a] quinoxalinium hydroxide, inner salt, 3-Hydroxy-4-methyl-2-(4-methylphenyl)-[1,2,3]triazolo[1,5-a] quinoxalinium hydroxide, inner salt,

3-Hydroxy-2-(6-methoxy-3-pyridinyl)-4-methyl-[1,2,3]triazolo [1,5-a]quinoxalinium hydroxide, inner salt, 3-Hydroxy-2-(4-trifluoromethylphenyl)-[1,2,3]triazolo[5,1-c] [1,2,4]benzotriazinium hydroxide, inner salt, 2-(6-Chloro-3-pyridinyl)-3-hydroxy-4-methyl-[ 1 ,2,3]triazolo[ 1 5-a]quinolinium hydroxide, inner salt, 4-Azetidinyl-3-hydroxy-2-(4-chlorophenyl)-[ 1 ,2,3]triazolo[ 1 ,Sa]quinoxalinium hydroxide, inner salt 2-(6-Chloro-3-pyridinyl)-3-hydroxy-4-methyl-5-nitro- [1 ,2,3]triazolo [1 ,5-a quinolinium hydroxide, inner salt, 2-(4-Chlorophenyl)-3-hydroxy-4-methyl-[1,2,3]triazolo[1,5-a] quinolinium hydroxide, inner salt, 2-(4-Chlorophenyl)-3-hydroxy-4-methyl-5-nitro-[ 1 ,2,3]triazolo[1 ,5-a]quinolinium hydroxide, inner salt, 5-Amino-2-(4-chlorophenyl)-3-hydroxy-4-methyl-[ 1 ,2,3]triazolo[ 1,5-a] quinolinium hydroxide, inner salt, 5-Amino-9-fluoro-3-hydroxy-2-(6-methyl-3-pyridinyl)-[ 1 ,2,3]triazolo[ 1 ,5-a quinolinium hydroxide, inner salt, 2-(4-Chlorophenyl)-3-hydroxy-5-methyl-[1,2,3]triazolo[1,5-a] quinolinium hydroxide, inner salt, 2-(4-Chlorophenyl)-3-hydroxy-5-nitro-[ 1 ,2,3]triazolo[ 1 ,5-a]quinolinium hydroxide, inner salt, 5-Amino-2-(4-chlorophenyl)-3-hydroxy-[ [1,2,3]triazolo[ 1,5-a] quinolinium hydroxide, inner salt, 5-(2-Aminoethyl)amino-2-(4-chlorophenyl)-3-hydroxy-[1,2,3]tr iazolo[1,5-a]- quinolinium hydroxide, inner salt, dihydrochloride, 4,5-Dihydro-3-hydroxy-5-oxo-4-propyl-2-[4-(trifluoromethyl)p henyl] - [1 ,2,3]triazolo[ 1 ,5-a]quinazolinium hydroxide, inner salt, 4-(2-Aminoethyl)-4,5-dihydro-3-hydroxy-5-oxo-2-[4-(trifluoro methyl)phenyl]- [1 ,2,3]triazolo[ 1 ,5-a]quinazolinium hydroxide, inner salt,

3-Hydroxy-5-(2-methoxyethylamino)-2-[4-(trifluoromethyl)phen yl]- [1 ,2,3]triazolo[ 1 ,5-a]quinolinium hydroxide, inner salt, 3-Hydroxy-5 -methoxy-2- [4-(trifluoromethyl)phenyl] 1 1,2,3 ]triazolo [1 ,5-a] quinolinium hydroxide, inner salt, 5-Azetidinylsulfonyl-2-(3-fluorophenyl)-3-hydroxyX 1 ,2,3]triazolo[ 1 ,5-a]quinolinium hydroxide, inner salt, 2-(3-Fluorophenyl)-3-hydroxy-[ 1,2,3]triazoio[l ,5-a]quinolinium hydroxide, inner salt, 2-(4-Fluorophenyl)-3-hydroxy-4-methyl-[1,2,3]triazolo[1,5-a] quinoxalinium hydroxide, inner salt, 2-(6-Chloro-3-pyridinyl)-3-hydroxy-4-methyl-[1,2,3]triazolo[ 1,5-a]quinoxalinium hydroxide, inner salt, 5-( 1 -Azetidinyl)-2-(6-chloropyridin-3-yl)-3-hydroxy-[ 1 ,2,3]triazolo[ 1 ,5-a]quinolinium hydroxide, inner salt, 5-(1-Azetidinyl)-3-hydroxy-4-methyl-2-[4-(trifluoromethyl)ph enyl]- [1 ,2,3]triazolo[ 1 ,5-a]quinolinium hydroxide, inner salt, 2-(4-Ethylphenyl)-3-hydroxy-4-methyl-[1,2,3]triazolo[1,5-a]q uinoxalinium hydroxide, inner salt, 2-(3-Chlorophenyl)-3-hydroxy-4-methyl-[ 1 ,2,3]triazolo[ 1 ,5-a]quinoxalinium hydroxide, inner salt, 2-(4-Chlorophenyl)-3-hydroxy-4-((4-morpholinyl)methyl)-[1,2, 3]triazolo[1,5- a]quinoxalinium hydroxide, inner salt, 2-(3,4-Difluorophenyl)-3-hydroxy-4-(1-imidazolyl)methyl-[1,2 ,3]triazolo[1,5- a]quinoxalinium hydroxide, inner salt, 3-Hydroxy-4-methyl-2-(4-trifluoromethoxyphenyl)-[1,2,3]triaz olo[1,5-a]- quinoxalinium hydroxide, inner salt, 2-(4-Fluoro-3-methyl)phenyl-3-hydroxy-4-methyl-[1,2,3]triazo lo[1,5-a]quinoxalinium hydroxide, inner salt, 2-(3-Fluoro-4-methyl)phenyl-3-hydroxy-4-methyl- [1,2,3]triazolo[1,5-a]quinoxalinium hydroxide, inner salt,

3-Hydroxy-4-methyl-2-(4-methylthiophenyl)- [1 ,2,3]triazolo[ 1,5-a] quinoxalinium - hydroxide, inner salt, 3-Hydroxy-4-methyl-2-(6-quinolyl)-[1 ,2,3]triazolo[ 1 ,5-a]quinoxalinium hydroxide, inner salt di (p-toluenesulfonate), 3-Hydroxy-4-methyl-2-(3-quinolyl)-[1 ,2,3]triazolo[ 1 ,5-a]quinoxalinium hydroxide, inner salt di (p-toluenesulfonate), 3-Hydroxy-4-methyl-2-(4-trifluoromethylthiophenyl)-[1,2,3]tr iazolo[1,5-a]- quinoxalinium hydroxide, inner salt p-toluenesulfonate, 2-(3-Chloro-4-methylphenyl)-3-hydroxy-4-methyl 1 ,2,3]triazolo[ 1 ,5-a]quinoxalinium hydroxide, inner salt p-toluenesulfonate, 2-(4-Cyclohexylphenyl)-3-hydroxy-4-methyl-[1,2,3]triazolo[1, 5-a]quinoxalinium hydroxide, inner salt p-toluenesulfonate, 3-Hydroxy-2-(4-isopropylphenyl)-4-methyl-[ [1 ,2,31triazolot 1 ,5-a]quinoxalinium hydroxide, inner salt p-toluenesulfonate, 3-Hydroxy-4-methyl-2-(3-methylphenyl)-[1,2,3]triazolo[1,5-a] quinoxalinium hydroxide, inner salt p-toluenesulfonate, 3-Hydroxy-5-methylsulfonylamino-2-(4-trifluoromethoxyphenyl) -[1,2,3]triazolo[1,5- a]quinolinium hydroxide, inner salt, 3-Hydroxy-4-((4-morpholinyl)methyl)- 2-(4-trifluoromethoxyphenyl)- [1,2,3]triazolo- [1,5-a]quinoxalinium hydroxide, inner salt, 3-Hydroxy-4-(imidazol- 1 -yl)methyl-2-(4-trifluoromethoxyphenyl)- [1 ,2,3lriazolo[1,5- a]quinoxalinium hydroxide, inner salt, 3-Hydroxy-4-(piperazinyl)methyl-2-(4-trifluoromethoxyphenyl) [1,2,3 Jriazolo [1,5-a] - quinoxalinium hydroxide, inner salt dihydrochloride, 4-Aminomethyl-3-hydroxy-2-(4-trifluoromethoxyphenyl)-[1,2,3] triazolo[1,5-a]- quinoxalinium hydroxide, inner salt dihydrochloride, 3-Hydroxy-5-(1-methylimidazol-4-yl)sulfonylamino-2-(4-triflu oromethoxyphenyl)- [1 ,2,3]triazolo[ 1 ,5-a]quinolinium hydroxide, inner salt, 2-(4-Fluorophenyl)-3-hydroxy-4-(imidazol-1-yl)methyl-[1,2,3] triazolo[1,5-a]- quinoxalinium hydroxide, inner salt,

2-(3-Fluoro-4-methoxyphenyl)-3-hydroxy-4-methyl- @ ,2,3]triazolo[ 1 ,5-a quinoxalinium hydroxide, inner salt, 3-Hydroxy-5-nitro-2-(4-methylphenyl)-[ 1 ,2,3]triazolo[ 1 ,5-a]quinoxalinium hydroxide, inner salt, 3-Hydroxy-5-methanesulfonamido-2-(4-methylphenyl)-[ @ ,2,31triazolo [ 1 ,5-a]- quinoxalinium hydroxide, inner salt, 3-Hydroxy-4-methyl-2-(4-methylphenyl)-5-nitro-[ 1,2,3 ]triazolo [1 ,5-a]quinoxalinium hydroxide, inner salt, 2-(4-Fluorophenyl)-3-hydroxy-5-methylsulphonylamino-[1,2,3]t riazolo[1,5- a]quinolinium hydroxide, inner salt, 2-(4-Fluorophenyl)-3-hydroxy-5-( 1 -methylimidazol-4-yl)sulphonylamino- [1,2,3]triazolo[1,5-a]quinolinium hydroxide, inner salt, and 2-(4-Fluorophenyl)-3-hydroxy-5-(3-pyridinyl)sulphonylamino- [1,2,3] triazolo[ 1,5- a]quinolinium hydroxide, inner salt.

Compounds of the invention can form pharmaceutically acceptable solvates and salts.

The compounds of the 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, oxalic, mandelic, tartaric and methanesulphonic acids.

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.

According to the invention there is also provided a process for the preparation of a compound of formula (I) which comprises (i) reacting a compound of formula (II): wherein n, R and A are as defined in formula (I), with the proviso that the atom in the 5-ring position (i.e. the atom attaching A to the phenyl ring) is not a nitrogen atom, with a compound of formula (III): <BR> <BR> <BR> <BR> <BR> <BR> A 1- T- <BR> <BR> <BR> <BR> <BR> <BR> ("I) in which Arl is as defined in formula (I) and T is a counter ion, followed by cyclisation of the resulting intermediate, for example, with acetic anhydride; or (ii) when A is X=Y where X is CR5 and R5 is nitro or NH2 and Y is CR6, reacting a corresponding compound of formula (I) in which R5 is hydrogen, with a nitrating agent (such as nitronium tetrafluoroborate), e.g. in a solvent such as dichloromethane, optionally followed by hydrogenation, e.g. over a palladium on charcoal catalyst; or (iii) when the atom in the 5-ring position is a nitrogen atom, reacting a compound of formula (IV): in which n, Rl and Ar' are as defined in formula (I), with diphenylphosphorylazide or with a chloroformate in the presence of a source of azide, e.g. sodium azide, and, if required,

cyclising the compound obtained, optionally in the presence of an acid chloride (e.g. phosgene) or a sulphonyl chloride (e.g. sulphuryl chloride); or (iv) when A is X=Y where X is N and Y is CR6, reacting a compound of formula (V): (V) wherein n, R1, R6 and Ar1 are as defined in formula (I), with a cyclising agent such as toluene sulphonic acid (e.g. in a solvent such as toluene at reflux) or phosphorus oxychloride; or (v) when A is X=Y where X is N and Y is N, reacting a compound of formula (VI): in which n, Rl and Arl are as defined in formula (I), with sodium nitrite; and optionally thereafter: converting the compound of formula (I) to a further compound of formula (I), and/or forming a pharmaceutically acceptable salt or solvate.

The reaction of compounds of formula (II) and (III) can be carried out using standard conditions. For example the diazonium salt of formula (III) can be prepared from the corresponding aniline and sodium nitrite in water at reduced temperature, for example at about 0 - 5"C. The resulting triazine intermediate can then be cyclised and dehydrated, for example by treating with pyridine and acetic anhydride.

Compounds of formula (II) where A is X'-Y' and X' is CH2 and Y' is CHR10 can be prepared from compounds of formula (VII): in which n, Rl and Rl° are as defined in formula (I), and R11 is an ester forming group, by hydrogenation followed by ester hydrolysis. The group R11 can be any ester forming group such as a C1-C6 alkyl group, for example methyl. Hydrogenation of compounds of formula (VII) can be carried out under conventional conditions, for example using 5% platinum on carbon (Pt/C) in ethanol. Ester hydrolysis can be carried out under conventional conditions, for example using sodium hydroxide.

Compounds of formula (II) where A is -C(=O)-NH- can be prepared by reacting compounds of formula (VIII): in which n and Rl are as defined in formula (I) with a compound of formula (IX): The reaction can be carried out in a suitable solvent such as methanol at elevated temperature, for example at reflux temperature.

Compounds of formula (VII) can be prepared from compounds of formula (X): in which n, Rl, Rl° and R11 are as defined in formula (VII) by reaction with a suitable chlorinating agent, such as phosphorus oxychloride, POC13, at reflux.

Compounds of formula (X) can be prepared by cyclisation of compounds of formula (XI): in which n, Rl, Rl° and R11 are as defined in formula (VII) and Rl2 is an ester forming group. Cyclisation can be carried out in diphenyl ether at elevated temperature, for example at about 250°C. Preferably R11 and Rl2 are the same and are both methyl or ethyl.

Compounds of formula (XI) in which Rl° is a hydrogen atom can be prepared by reacting the corresponding aniline with a compound of formula (XII): in which R11 and Rl2 are as defined in formula (XI). The reaction is carried out in a suitable solvent such as methanol at elevated temperature, such as reflux.

Compounds of formula (XI) in which Rl° represents a hydrogen atom or a C1-C6 alkyl or C3-C7 cycloalkyl group can be prepared by reacting the corresponding aniline with a compound of formula (XIII):

in which R11 and Rl2 are as hereinbefore defined and Rl° represents a hydrogen atom or a C1-C6 alkyl or C3-C7 cycloalkyl group. The reaction is carried out in a suitable solvent such as dichloromethane in the presence of a drying agent such as magnesium sulphate at reflux.

Compounds of formula (IV) can be prepared by reacting a compound of formula (XIV): (XIV) in which n, R1 and R12 are as hereinbefore defined, with a compound of formula (XV), Arl-NH2, in which Arl is as hereinbefore defined, in the presence of sodium nitrite to form an intermediate that can be cyclised and dehydrated, for example by treating with pyridine and acetic anhydride, followed by ester hydrolysis.

Compounds of formula (V) can be prepared by reacting a compound of formula (VI) as defined above with a compound of formula (XVI), R6COCl, in which R6is as defined in formula (I).

An alternative, preferred method for preparing the compounds of formula (V) involves reacting a compound of formula (XVII) or a salt thereof (e.g. a lithium salt):

(XVII) in which n, R1 and R6 are as hereinbefore defined, with a compound of formula (III) as defined above, followed by cyclisation and dehydration of the resulting intermediate, for example, by treating with pyridine and acetic anhydride.

Compounds of formula (XVII) can be prepared by reacting a compound of formula (XVIII): where the groups R13 both represent a hydrogen or oxygen atom and n, R1 and R6 are as hereinbefore defined, with a compound of formula (IX) as specified above under an atmosphere of hydrogen and in the presence of a catalyst such as palladium on charcoal.

Compounds of formula (XVIII) can be prepared by reacting a compound of formula (XIX): in which n, Rl and Rl3 are as defined in formula (XVIII), with a compound of formula (XVI) as defined above.

Compounds of formula (VI) can be prepared from compounds of formula (IV) by reaction with, for example, diphenylphosphoryl azide in the presence of tertiary butyl alcohol followed by reaction with an acid such as trifluoroacetic acid.

Compounds of formula (III), (VIII), (IX), (XII), (XIII), (XIV), (XV), (XVI) and (XIX) are commercially available or can be prepared from commercially available starting materials using known procedures.

All novel intermediates form a further aspect of the invention.

Compounds of formula (I) can be converted into further compounds of formula (I) using standard procedures. For example compounds of formula (I) where A is CHRI°-CHRl° can be converted to compounds of formula (I) where A is CR5=CR6 by oxidation using, for example, palladium on carbon in dimethylacetamide (Pd/C/DMA), manganese dioxide in trichloromethane (MnO2/CHCl3) or 2,3-dichloro-5,6-dicyano- 1,4-benzoquinone in toluene (DDQ/toluene), each at elevated temperature, for example, at reflux temperature, or using bromine/pyridine/dichloromethane (CH2C12) at ambient temperature. Compounds of formula (I) where A is C(=O)-NH can be converted to compounds of formula (I) where A is C(=O)-N-alkyl by treatment with a base followed by a suitable alkylating agent, for example methyl iodide.

Compounds of formula (I) where X is a group CR5 where R5 is NR7R8 and Y is CH can be prepared by reaction of a compound of formula (XX):

in which Ar is as defined in formula (I) with an amine HNR7R8 in the presence of a palladium catalyst such as tris(dibenzylideneacetone)dipalladium(0), a base such as sodium tert-butoxide and a phosphine ligand such as bis(diphenylphosphino)- 1,1 -binaphthyl in an organic solvent such as toluene, for example at reflux.

Compounds of formula (XX) can be prepared by reaction of a compound of formula (I) where X is CH and Y is CH with bromine in an appropriate solvent such as dichloromethane and in the presence of a base, for example pyridine.

Compounds of formula (XX) can also be formed directly from a compound of formula (I) where X' is CH2 and Y' is CH2 by reaction with bromine in an appropriate solvent such as dichloromethane and in the presence of a base, for example, pyridine.

Compounds of formula (I) where X is a group CR5 where R5is NR7R8 and Y is N can be prepared by reaction of a compound of formula (XXI): in which Arl is as defined in formula (I) with an amine HNR7R8, for example with heating.

Compounds of formula (XXI) can be prepared by reaction of a compound of formula (I) in which A is Y'-X' where Y' is C=O and X' is NH with a chlorinating agent such as PO(ilat reflux.

Compounds of formula (I) in which A is X=Y where X is CR5 and R5 is NR7R8 (R7is hydrogen and R8 is an optionally-substituted phenyl-, pyridinyl- or imidazolyl-sulphonyl

group or an optionally substituted alkylsulphonyl group) and Y is CH can be prepared by reacting a corresponding compound of formula (I) in which R5 is NH2, with a compound of formula (XXII), R8SO2Cl, in pyridine where R8 is as hereinabove defined.

Compounds of formula (I) in which A is X=Y where X is CR5 and R5 is hydrogen and Y is CR6 and R6 is bromomethyl (CH2Br) can be prepared by reacting a corresponding compound of formula (I) in which R6 is methyl, with N-bromosuccinimide benzoyl peroxide in methyl formate followed by heating in tetralin. The compound of formula (I) obtained may in turn be converted into a further compound of formula (I) in which R6 is CH2NR'R' by reaction with a compound of formula (XXIII), R'R'NH, where R' is as defined above, in a solvent such as tetrahydrofuran.

It will be appreciated by those skilled in the art that in the process described above the functional groups of intermediate compounds may need to be protected by protecting groups.

Functional groups which it is desirable to protect include hydroxyl, amino and carboxylic acid. Suitable protecting groups for hydroxyl include organosilyl groups (e.g. tert-butyldimethylsilyl, tert-butyldiphenylsilyl or trimethylsilyl), benzyl and tetrahydro- pyranyl. Suitable protecting groups for amino include tert-butoxycarbonyl or benzyloxy carbonyl. Suitable protecting groups for carboxylic acid include C1-C6 alkyl or benzyl esters. The protection and deprotection of functional groups may take place before or after a reaction step.

The use of protecting groups is fully described in 'Protective Groups in Organic Chemistry', edited by J. W. F. McOmie, Plenum Press (1973), and 'Protective Groups in Organic Synthesis', 2nd edition, T. W. Greene & P. G. M. Wutz, Wiley-Interscience (1991).

According to the invention there is further provided the compounds of the invention for use in therapy as pharmaceuticals. In particular the compounds of the invention possess anti- allergic and anti-inflammatory activity, for example as shown in the tests described below.

The compounds of the invention are thus indicated for use in the treatment of allergic and inflammatory diseases/disorders of the airways such as asthma (e.g. bronchial asthma, allergic asthma, intrinsic asthma, extrinsic asthma and dust asthma), particularly chronic or inveterate asthma (e.g. late asthma and airway hyper-responsiveness) and bronchitis.

Further, the compounds of the invention are indicated in the treatment of diseases/disorders including inflammations/allergies such as rhinitis, including all conditions characterised by inflammation of the nasal mucus membrane, such as acute rhinitis, allergic rhinitis, atrophic rhinitis, chronic rhinitis including rhinitis caseosa, hypertrophic rhinitis, rhinitis purulenta and rhinitis sicca, rhinitis medicamentosa, membranous rhinitis including croupous, fibrinous and pseudomembranous rhinitis, scrofoulous rhinitis, seasonal rhinitis including rhinitis nervosa (hay fever) and vasomotor rhinitis.

The compounds of the invention are also indicated for use in the treatment of chronic allergic disorders, atopic dermatitis, cutaneous eosinophilias, eosinophilic fascitis, hyper IgE syndrome, vernal conjunctivitis, systemic lupus erythematosis, thyroiditis, lepromatous leprosy, sezary syndrome, chronic graft versus host disease, myasthenia gravis and idiopathic thrombocytopenia pupura.

The compounds of the invention may also have activity in both the prophylactic and therapeutic treatment of acquired immunodeficiency syndrome (AIDS), the prevention of chronic rejection of allografts mediated by humoral immunity, and in the treatment of autoimmune diseases (such as multiple sclerosis and rheumatoid arthritis) and oestrogen- dependent cancers (e.g. breast cancer).

Of particular interest amongst the above indications are the use of the compounds of the invention in asthma, especially the prophylaxis of asthma, and in rhinitis, most particularly allergic rhinitis and seasonal rhinitis including rhinitis nervosa (hay fever).

According to a further aspect of the present invention, there is provided a method of treatment or prophylaxis of an allergic or an inflammatory disorder, which method comprises administration of a therapeutically effective amount of a compound of formula (I) as hereinbefore defined, or a pharmaceutically acceptable salt or solvate thereof, to a person suffering from, or susceptible to such a disorder.

The invention further provides the use of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof in the manufacture of a medicament for the treatment or prophylaxis of the above disorders, in particular asthma and rhinitis.

Administration of the compounds of the invention may be topical (for example by inhalation to the lung). The compounds of the invention may be inhaled as a dry powder which may be pressurised or non-pressurised.

In non-pressurised powder compositions, the active ingredient in finely divided form may be used in admixture with a larger sized pharmaceutically acceptable inert carrier.

The composition may alternatively be pressurised and contain a compressed gas, e.g. nitrogen, or a liquefied gas propellant. In such pressurised compositions, the active ingredient is preferably finely divided. The pressurised composition may also contain a surface active agent. The pressurised compositions may be made by conventional methods.

The compounds of the invention may be administered systemically (for example by oral administration to the gastrointestinal tract). The active ingredient may be formulated together with known adjuvants, diluents or carriers using conventional techniques to produce tablets or capsules for oral administration to the gastrointestinal tract.

Examples of suitable adjuvants, diluents or carriers for oral administration in the form of tablets, capsules and dragees include microcrystalline cellulose, calcium phosphate, diatomaceous earth, a sugar such as lactose, dextrose or mantel, talc, stark acid, starch, sodium bicarbonate and/or gelatine.

According to a further aspect of the invention there is provided a pharmaceutical composition comprising a compound of formula (I) as hereinbefore defined or a pharmaceutically acceptable salt or solvate thereof, in association with a pharmaceutically acceptable adjuvant, diluent or carrier.

Suitable doses for administration topical or orally are in the range 0.01 to 30mgkg~lday~l, for example 0.3mgkg-1day-1.

The invention will now be further illustrated by reference to the following examples.

Example 1 2-(4-Chlorophenyl)-2,4-dihydro-3-hydroxy-[1 ,2,3]triazolo[1,5-a]indolinium hydroxide, inner salt.

To a stirred solution of 4-chloroaniline (3. 19g) in a mixture of water (50ml) and concentrated hydrochloric acid (lOml) at 0 to -50C was added portionwise a solution of sodium nitrite (1.8g) in water (5ml). The solution was stirred 30 minutes at 0 to -50C and then was added portionwise to a solution of indoline-2-carboxylic acid (4.08g) in pyridine (50ml) at 0 to -50C. The solution was stirred for 0.5 hour at 0 to -50C, diluted with water and then was filtered washing with water. The solid was dissolved in dichloromethane, dried over magnesium sulphate and concentrated in vacuo. To the residue was added pyridine (50ml) then acetic anhydride (5ml) and the solution was stirred for 2 hours. The reaction mixture was diluted with diethyl ether and filtered. Purification by chromatography on silica gel (dichloromethane : methanol/ 20:1 then 10:1) followed by recrystallisation gave the title compound (1.45g) as a pale pink solid.

MS APCI (+ve) 284 ((M+H)+). <BR> <BR> <P>1HNMR (CDCl3) 54.09 (2H, s), 7.52 (4H, m), 7.65 (lH, d), 7.86 (lH, d), 8.13 (2H, m).

Example 2 2,4-Dihydro-3-hydroxy-2-[4-(trifluoromethyl)phenyl] -[1,2,3]triazolo[1,5-a]indolinium hydroxide, inner salt.

Prepared by the route of Example 1 using 4-(trifluoromethyl)aniline (4.03g) to give the title compound (3.55g) as a pale solid.

MS APCI (+ve) 318 ((M+H)+).

'H NMR (CDCl3) 54.11 (2H, s), 7.55 (2H, m), 7.57 (2H, d), 7.67 (1H, m), 7.89 (1H, m), 8.37 (2H, d).

Example 3 4,5-Dihydro-3-hydroxy-2-[4-(trifluoromethyl)phenyl]-[1,2,3]t riazolo[1,5-a]- quinolinium hydroxide, inner salt.

To a stirred solution of 4-(trifluoromethyl)aniIine (12.08g) in a mixture of water (150ml), tetrahydrofuran (60ml) and concentrated hydrochloric acid (20ml) at 0 to -50C was added portionwise a solution of sodium nitrite (5.43g) in water (50ml). The solution was stirred 15 minutes at 0 to -50C and then was added portionwise to a solution of 1,2,3,4-tetrahydro- quinoline-2-carboxylic acid (13.3g - Chem. Ber. 61, 1928, 2377) in pyridine (150ml) at 0 to -5°C. The solution was stirred for 1 hour at 0 to -50C and then was allowed to warm to room temperature. Water was added and the solution was extracted with ethyl acetate (twice), dried over magnesium sulphate and concentrated in vacuo. To the residue was added pyridine (90ml) then acetic anhydride (10ml) and the solution was stirred for 1 hour.

The reaction mixture was diluted with diethyl ether and filtered to give the title compound (12.25g) as a yellow solid. m.p. 216-218°C MS APCI (+ve) 332 ((M+H)+).

1H NMR (CDCl3) 6 3.08 (4H, s), 7.41 (3H, m), 7.77 (2H, d), 8.02 (1H, m), 8.42 (2H, d).

Example 4 2-(4-Chlorophenyl)-4,5-dihydro-3-hydroxy-[1,2,3]triazolo[1,5 -a]quinolinium hydroxide, inner salt.

Prepared by the route of Example 3 using 4-chloroaniline (3.06g) to give the title compound (0.752g) as a pale yellow solid. m.p. 166-168°C MS APCI (+ve) 298 ((M+H)+).

'H NMR (CDC13) 63.07 (4H, s), 7.43 (5H, m), 8.00 (1H, m), 8.19 (2H, m).

Example 5 2-(4-Chloro-2-methylphenyl)-4,5-dihydro-3-hydroxy-[1,2,3]tri azolo[1,5-a]quinolinium hydroxide, inner salt.

Prepared by the route of Example 3 using 4-chloro-2-methylaniline (7.08g) to give the title compound (4.452g) as a pale orange solid. m.p. 162-163°C MS APCI (+ve) 312 ((M+H)+).

1H NMR (CDC13) 8 2.35 (3H, s), 3.09 (4H, s), 7.32 (1H, m), 7.39 (5H, m), 7.91 (lH, m).

Example 6 4,5-Dihydro-3-hydroxy-5-oxo-2-[4-(trifiuoromethyl)phenyl] [1,2,3]triazolo[1 ,5-a]- quinazolinium hydroxide, inner salt.

(a) 4-Oxo-1,2,3,4-tetrahydroquinazoline-2-carboxylic acid To a stirred solution of anthranilamide (45g) in methanol (900ml) was added glyoxylic acid monohydrate (30.6g) and the reaction mixture was refluxed for 1 hour. The solution was

cooled to 0 to -50C for several hours, then filtered to give the subtitle compound (28. lg) as a white solid. m.p. 184-185°C MS APCI (+ve) 193 ((M+H)+). <BR> <BR> <BR> <BR> <BR> <BR> <P>(b) 4,5-Dihydro-3-hydroxy-5-oXo-2-[4-(trifluoromethyl)phenyl]-[1 ,2,3]triazolo[1,5-a]- quinazolinium hydroxide, inner salt.

To a stirred solution of 4-(trifluoromethyl)aniline (16.1g) in a mixture of water (145ml), tetrahydrofuran (65ml) and concentrated hydrochloric acid (35ml) at 0 to -50C was added portionwise a solution of sodium nitrite (7.25g) in water (80ml). The solution was stirred 15 minutes at 0 to -50C and then was added portionwise to a solution of 4-oxo-1,2,3,4- tetrahydroquinazoline-2-carboxylic acid (19.2g) in pyridine (145ml) and water (100ml) at 0 to -5 CC. The solution was stirred for 1 hour at 0 to -50C and then was allowed to warm to room temperature. The solid was filtered washing with water then was azeotroped with toluene. To the residue was added pyridine (180ml) then acetic anhydride (25ml) and the solution was stirred for 1 hour. The reaction mixture was diluted with diethyl ether and filtered to give the title compound (6.8g) as a yellow solid. m.p.>250°C MS APCI (+ve) 347 ((M+H)+).

1H NMR (DMSO-d6) # 7.83 (1H, t), 8.03 (3H, m), 8.28 (1H, d), 8.33 (1H, d), 8.50 (2H, d), 12.90 (1H, br s).

Example 7 5-Chloro-3-hydroxy-2-[4-(trifluoromethyl)phenyl]-[1,2,3]tria zolo[1,5-a]quinazolinium hydroxide, inner salt.

A solution of 4,5-dihydro-3-hydroxy-5-oxo-2- [4-(trifluoromethyl)phenyl]- [1,2,3]triazolo[l ,5-a]quinazolinium hydroxide, inner salt (Example 6) (1.76g) in phosphorus oxychloride (20ml) was refluxed for 2 hours before being concentrated in vacuo. The residue was quenched with water then basified with solid sodium hydrogen carbonate. The solution was extracted with ethyl acetate (twice), dried over magnesium sulphate and concentrated in vacuo. The solid was washed with ethyl acetate to give the title compound (1.48g) as a yellow solid.

Example 8 3-Hydroxy-2-[4-(trifluoromethyl)phenyl] -[1,2,3]triazolo[1,5-a]quinazolinium hydroxide, inner salt.

To a solution of 5-chloro-3-hydroxy-2-[4-(trifluoromethyl)phenyl]-[ 1 ,2,3]triazolo[ 1,5- a]quinazolinium hydroxide, inner salt (Example 7) (lg) in ethanol (150ml) was added sodium borohydride (1.04g) and the reaction mixture was stirred for 2 hours. The solution

was quenched with ammonium chloride solution, extracted with ethyl acetate (twice), dried over magnesium sulphate and concentrated in vacuo. The residue was recrystallised from methanol to give the title compound (0.33g) as a yellow solid. m.p. >255°C MS APCI (+ve) 331 ((M+H)+).

1H NMR (DMSO-d6) 3 7.79 (1H, t), 7.95 (1H, t), 8.16 (2H, d), 8.28 (2H, m), 8.40 (2H, d), 9.08 (1H, s).

Example 9 3-Hydroxy-2-[4-(trifluoromethyl)phenyl]-[1,2,3]triazolo[1,5- a]quinolinium hydroxide, inner salt. <BR> <BR> <BR> <BR> <P>A solution of 4,5-dihydro-3-hydroxy-2- [4-(trifluoromethyl)phenyl]- [1,2,3]triazolo[1,5-a]- quinolinium hydroxide, inner salt (Example 3) (9.6g) and 10% palladium on carbon (lg) in a mixture of dimethylacetamide (loom) and cyclohexene (100ml) was heated at 140°C for 2 days. After allowing to cool the solution was diluted with a mixture of water and ethyl acetate and filtered through Celite. The organic layer was separated, dried over magnesium sulphate and concentrated in vacuo. Purification by chromatography on silica gel (ethyl acetate) gave the title compound (5.54g) as a yellow solid. m.p. 174-176"C MS APCI (+ve) 330 ((M+H)+).

1H NMR (CDCl3) 6 7.52 (1H, d), 7.69 (1H, d), 7.84 (2H, m), 7.99 (2H, m), 8.08 (1H, d), 8.54 (3H, m).

Example 10 3-Hydroxy-S-(1 -methylethyl)-2 [4-(trifluoromethyl)phenyl]- [1,2,3]triazolo[1,5-a]- quinazolinium hydroxide, inner salt.

To a solution of 5-chloro-3-hydroxy-2-[4-(trifluoromethyl)phenyl]-[1,2,3]tria zolo[1,5- a]quinazolinium hydroxide, inner salt (Example 7) (lg) in tetrahydrofuran (150ml) was added dropwise isopropyl magnesium chloride (3.4ml - 2M solution in tetrahydrofuran) and the solution was stirred overnight. The solution was quenched with ammonium chloride solution, extracted with dichloromethane (twice), dried over magnesium sulphate and concentrated in vacuo. Purification by chromatography on silica gel (acetone to acetone : methanol/ 10:1) followed by recrystallisation from ethyl acetate gave the title compound (0.04g) as a white solid. m.p. 255°C MS APCI (+ve) 373 ((M+H)+).

1H NMR (DMSO-d6) 8 1.41 (6H, d), 2.99 (1H, m), 7.77 (1H, t), 7.90 (1H, t), 8.10 (2H, d), 8.17 (3H, m), 8.27 (1H, d).

Example 11 4,5-Dihydro-9-fluoro-3-hydroxy-2-[4-(trifluoromethyl)phenyl] -[1,2,3]triazolo[1,5-a]- quinolinium hydroxide, inner salt.

(a) 8-Fluoro-4-hydroxy-quinoline-2-carboxylic acid, methyl ester.

To a solution of 2-fluoroaniline (18.2g) in methanol (300ml) was added dimethyl acetylenedicarboxylate (23.3) and the reaction mixture was refluxed for 8 hours. The solution was allowed to cool then concentrated in vacuo. The oil was dissolved in diphenyl ether (20ml) and added portionwise to a flask containing diphenyl ether (180ml) at 2500 C.

After complete addition the reaction mixture was maintained at 2500C for a further 10 minutes. The solution was allowed to cool then was poured into iso-hexane (1 litre) before being filtered to give the subtitle compound (29.6g) as a yellow solid.

(b) 4-Chloro-8-fluoro-quinoline-2-carboxylic acid, methyl ester.

A solution of 8-fluoro-4-hydroxy-quinoline-2-carboxylic acid, methyl ester (20.3g) in phosphorus oxychloride (80ml) was refluxed for 10 hours before being concentrated in vacuo. The residue was quenched with water then basified with sodium hydrogen carbonate solution. The solution was filtered and dried to give the subtitle compound (50.5g) as a tan solid.

MS APCI (+ve) 240 ((M+H)+).

(c) 8-Fluoro-1,2,3,4- tetrahydroquinoline -2-carb oxylic acid.

A solution of 4-chloro-8-fluoro-quinoline-2-carboxylic acid, methyl ester (6.3g) and 5% platinum on carbon (0.5g) in ethanol (300ml) was hydrogenated at 5 bar for 2 hours. The reaction mixture was filtered through Celite then concentrated in vacuo. The residue was dissolved in methanol (150ml) and sodium hydroxide (3.46g) in water (50ml) was added.

The reaction mixture was stirred for 30 minutes then hydrochloric acid (100ml - 2M) was added. The solution was extracted with ethyl acetate (twice), dried over magnesium sulphate and concentrated in vacuo to give the subtitle compound (4.5g) as a tan solid.

MS APCI (-ve) 194 ((M-H)+).

(d) 4,5-Dihydro-9-fluoro-3-hydroxy-2-[4-(trifluoromethyl)phenyl] -[1,2,3]triazolo[1,5- a]quinolinium hydroxide, inner salt.

Prepared by the route of Example 3 using 8-fluoro-1,2,3,4-tetrahydroquinoline-2- carboxylic acid (4.5g) and 4-(trifluoromethyl)aniline (3.7g) to give the title compound (3.15g) as a pale yellow solid.

MS APCI(+ve) 350 ((M+H)+).

1H NMR (DMSO-d6) # 2.89 (2H, t), 3.10 (2H, t), 7.47 (3H, m), 7.97 (2H, d), 8.38 (2H, d).

Example 12 9-Fluoro-3-hydroxy-2-[4-(trifluoromethyl)phenyl] -[1,2,3]triazolo[1,5-a] quinolinium hydroxide, inner salt.

Prepared by the route of Example 9 using 4,5-dihydro-9-fluoro-3-hydroxy-2-[4- (trifluoromethyl)phenyl]-[1,2,3]triazolo[1,5-a]quinolinium hydroxide, inner salt (Example 11) (2.5g) to give the title compound (0.212g) as a yellow solid. m.p. 201-203°C MS APCI(+ve) 348 ((M+H)+).

1H NMR (DMSO-d6) # 7.50 (1H, d), 7.74 (3H, m), 7.86 (1H, d), 8.00 (2H, d), 8.45 (2H, d).

Example 13 4,5-Dihydro-3-hydroxy-5-oxo-4-methyl-2-[4-(trifluoromethyl)p henyl]- [1,2,3]triazolo[1,5-a]quinazolinium hydroxide, inner salt.

To a solution of 4,5-dihydro-3-hydroxy-5 -oxo-2-[4-(trifluoromethyl)phenyl]- [1,2,3]triazolo[1,5-a]quinazolinium hydroxide, inner salt (Example 6) (2.2g) and sodium hydride (0.25g - 60% dispersion in mineral oil) in dimethylformamide (1 00ml) was added methyl iodide (0.4ml) and the reaction mixture was stirred for 2 hours. The solution was quenched with water, filtered and dried in vacuo. Recrystallisation from methanol gave the title compound (1.54g) as a yellow solid. m.p. 248-250°C MS APCI (+ve) 361 ((M+H)+) 1H NMR (DMSO-d6) 6 3.83 (3H, s), 7.84 (1H, t), 8.00 (2H, d), 8.05 (1H, d,t), 8.31 (1H, d,d), 8.35 (1H, d), 8.48 (2H, d).

Example 14 6,9-Difluoro-4,5-dihydro-3-hydroxy-2-[4-(trifluoromethyl)phe nyl]-[1,2,3]triazolo[1,5- a]quinolinium hydroxide, inner salt.

(a) 5,8-Difluoro-4-hydroxy-quinoline-2-carboxylic acid, methyl ester.

To a solution of 2,5-difluoroaniline (11.62g) in methanol (150ml) was added dimethyl acetylenedicarboxylate (12.8) and the reaction mixture was refluxed for 8 hours. The solution was allowed to cool then concentrated in vacuo. The oil was dissolved in diphenyl ether (120ml), carefully heated to 2500C and maintained at 2500C for 10 minutes. The solution was allowed to cool then was poured into iso-hexane (1 litre) before being filtered to give the subtitle compound (17g) as a brown solid.

(b) 4-Chloro-5,8-difluoro-quinoline-2-carboxylic acid, methyl ester.

A solution of S,8-difluoro-4-hydroxy-quinoline-2-carboxylic acid, methyl ester (17g) in phosphorus oxychloride (70ml) was refluxed for 10 hours before being concentrated in vacua. The residue was quenched with water then basified with sodium hydrogen carbonate solution. The solution was filtered and dried in vacuo to give the subtitle compound (15g) as a tan solid.

MS APCI (+ve) 258 ((M+H)+).

(c) S,8-Difluoro-1,2,3,4-tetrahydroquinoline-2-carboxylic acid.

A solution of 4-chloro-5,8-difluoro-quinoline-2-carboxylic acid, methyl ester (15g), 5% platinum on carbon (lug) in ethanol (500ml) was hydrogenated at 5 bar for 4 hours. The reaction mixture was filtered through Celite then concentrated in vacuo. The residue was dissolved in ethanol (200ml) and sodium hydroxide (7g) in water (100ml) was added. The reaction mixture was stirred for 30 minutes then hydrochloric acid (200ml - 2M) was added. The solution was extracted with ethyl acetate (twice), dried over magnesium sulphate and concentrated in vacuo to give the subtitle compound (12g) as a brown solid.

(d) 6,9-Difluoro-4,5-dihydro-3-hydroxy-2-[4-(trifluoromethyl)phe nyl]- [1,2,3]triazolo[1 ,5-a]quinolinium hydroxide, inner salt.

Prepared by the route of Example 3 using 5,8-difluoro- 1 ,2,3,4-tetrahydroquinoline-2- carboxylic acid (5.325g) and 4-(trifluoromethyl)aniline (4.03 g) to give the title compound (2.65g) as a tan solid. m.p. >260°C MS APCI (+ve) 368 ((M+H)+) 1H NMR (DMSO-d6) 6 2.91 (2H, t), 3.06 (2H, t), 7.52 (2H, m), 7.97 (2H, d), 8.37 (2H, d) Example 15 4,5-Dihydro-9-fluoro-3-hydroxy-2-(3-pyridinyl)- [1,2,3]triazolo[1,S-a] quinolinium hydroxide, inner salt.

Prepared by the route of Example 3 using 8-fluoro-1,2,3,4-tetrahydroquinoline-2- carboxylic acid (Example 11c) (4.9g) and 3-aminopyridine (2.35g) to give the title compound (3.5g) as a pale orange solid. m.p. 183-185°C MS APCI (+ve) 283 ((M+H)+) 1H NMR (DMSO-d6) # 2.90 (2H, t), 3.11 (2H, t), 7.47 (3H, m), 7.65 (1H, d,d), 8.45 (1H, m), 8.65 (1H, d), 9.28 (1H, d) Example 16 2-(6-Chloro-3-pyridinyl) -9-fluoro-4,5-dihydro-3-hydroxy-[1,2,3]triazolo[1,5- a]quinolinium hydroxide, inner salt.

Prepared by the route of Example 3 using 8-fluoro-1,2,3,4-tetrahydroquinoline-2- carboxylic acid (Example 1 lc) (4.9g) and 5-amino-2-chloropyridine (3.21g) to give the title compound (1.7g) as a pale orange solid. m.p. 227-229°C MS APCI (+ve) 317 ((M+H)+) 1H NMR (DMSO-d6) 3 2.90 (2H, t), 3.11 (2H, t), 7.47 (3H, m), 7.78 (1H, d), 8.54 (1H, d,d), 9.16(1H, d)

Example 17 6,9-Difluoro-3-hydroxy-2-[4-(trifluoromethyl)phenyl]-[1,2,3] triazolo[1,5-a]- quinolinium, hydroxide inner salt.

A solution 6,9-difluoro-4,5-dihydro-3-hydroxy-2-[4-(trifluoromethyl)phe nyl]- [1,2,3]triazolo[1,5-a]quinolinium hydroxide, inner salt (Example 14) (2g) and DDQ (1.86g) in toluene (150ml) was refluxed overnight. Purification by chromatography on silica gel (ethyl acetate : iso-hexane/ 2:1) followed by recrystallisation from ethyl acetate gave the title compound (0.98g) as yellow needles. m.p. 243-2450C MS APCI (+ve) 366 ((M+H)+) lH NMR (CDCl3) 6 7.37 (3H, m), 7.75 (1H, d), 7.81 (2H, d), 8.49 (2H, d) Example 18 4,5-Dihydro-3-hydroxy-4-methyl-2-[4-(trifluoromethyl)phenyl] -[1,2,3]triazolo[1,5-a]- quinolinium hydroxide, inner salt.

(a) 4-Hydroxy-3-methyl-quinoline-2-carboxylic acid, ethyl ester.

To a solution of aniline (11.3ml) and magnesium sulphate (lOg) in dichloromethane (80ml) was added diethyl oxalpropionate (25g) and the reaction mixture was refluxed for 48h hours. The solution was concentrated in vacuo and purified by chromatography on silica gel (iso-hexane : diethyl ether/ 20: 1). The intermediate was dissolved in diphenyl ether (30ml) and added portionwise to a flask containing diphenyl ether (100ml) at 2500C. After complete addition the reaction mixture was maintained at 2500C for a further 10 minutes.

The solution was allowed to cool then was poured into iso-hexane (1 litre) before being filtered to give the subtitle compound (17.7g) as a white solid.

MS APCI (+ve) 232 ((M+H)+).

LAb 4-Chloro-3-methyl-quinoline-2-carboxylic acid, ethyl ester.

A solution of 4-hydroxy-3-methyl-quinoline-2-carboxylic acid, ethyl ester (17g) in phosphorus oxychloride (70ml) was refluxed for 2 hours before being concentrated in vacuo. The residue was quenched with water then basified with sodium hydrogen carbonate solution. The solution was extracted with ethyl acetate, dried over magnesium sulphate and concentrated in vacuo to give the subtitle compound (17g) as a pale tan solid.

(c) 3-Methyl-1,2,3,4-tetrahydroquinoline-2-carboxylic acid.

A solution of 4-chloro-3-methyl-quinoline-2-carboxylic acid, ethyl ester (17g), 5% platinum on carbon (lg) in ethanol (250ml) was hydrogenated at 5 bar for 4 hours. The reaction mixture was filtered through Celite then concentrated in vacuo. The residue was dissolved in ethanol (200ml) and sodium hydroxide (8.18g) in water (100ml) was added.

The reaction mixture was stirred for 4 hours then hydrochloric acid (240ml - 2M) was added. The solution was extracted with ethyl acetate (twice), dried over magnesium sulphate and concentrated in vacuo to give the subtitle compound (13.2g) as a brown solid.

MS APCI (+ve) 192 ((M+H)+).

(d) 4,5-Dihydro-3-hydroxy-4-methyl-2-[4-(trifluoromethyl)phenyl] -[1,2,3]triazolo[1,5- a]quinolinium hydroxide, inner salt.

Prepared by the route of Example 3 using 3-methyl-1,2,3,4-tetrahydroquinoline-2- carboxylic acid (5.68g) and 4-(trifluoromethyl)aniline (4.03 g) to give the title compound (2.51g) as a yellow solid. m.p. 210-212°C MS APCI (+ve) 346 ((M+H)+) H NMR (CDCl3) #2.85 (1H, d,d), 3.19 (1H, d,d), 3.48 (1H, sextet), 7.42 (3H, m), 7.77 (2H, d), 8.02 (lH, m), 8.42 (2H, d) Example 19 3-Hydroxy-4-methyl-2-[4-(trifluoromethyl)phenyl]-[1,2,3]tria zolo[1,5-a]quinolinium hydroxide, inner salt.

Prepared by the route of Example 9 using 4,5-dihydro-3-hydroxy-4-methyl-2-[4- (trifluoromethyl)phenyl]-[l ,2,3]triazolo[l ,5-a]quinoiinium hydroxide, inner salt (Example 18) (1.lg) to give the title compound (0.745g) as a yellow solid. m.p. 216-218°C MS APCI (+ve) 344 ((M+H)+) H NMR (CDCl3) #2.79 (3H, s), 6.97 (1H, s), 7.65 (2H, m), 7.71 (1H, m), 7.81 (2H, d), 8.50 (3H, m)

Example 20 2-(6-Chloro-3-pyridinyl) -9-fluoro-3-hydroxy-[1,2,3]triazolo[1,5-a]quinolinium hydroxide, inner salt.

A solution 2-(6-chloro-3-pyridinyl) -9-fluoro-4,S-dihydro-3-hydroxy- [I ,2,3]triazolo[ 1,5- a]quinolinium hydroxide, inner salt (Example 16) (0.46g) and manganese dioxide (5g) in chloroform (100ml) was refluxed for 4 days. The reaction mixture was filtered then purified by chromatography on silica gel (ethyl acetate) to give the title compound (0. 16g) as a yellow solid. m.p. 232-235°C MS APCI (+ve) 315 ((M+H)+) 1H NMR (CDCl3) 8 7.28 (1H, m), 7.46 (2H, m), 7.62 (2H, m), 7.69 (1H, d), 8.72 (1H, d,d), 9.35 (1H, d) Example 21 9-Fluoro-3-hydroxy-2-(3-pyridinyl)-[1,2,3]triazolo[1,5-a]qui nolinium hydroxide, inner salt.

Prepared by the route of Example 17 using 4,5-dihydro-9-fluoro-3-hydroxy-2-(3-pyridinyl) [1,2,3]triazolo[1,5-a]quinolinium hydroxide, inner salt (Example 15) (l.lg) to give the title compound (0.130g) as a yellow solid. m.p. 200-203°C MS APCI (+ve) 281 ((M+H)+) 1H NMR (CDCl3) 8 7.26 (1H, m), 7.47 (2H, m), 7.60 (2H, m), 7.70 (1H, d), 8.69 (2H, m), 9.52 (1H, d) Example 22 4,5-Dihydro-3-hydroxy-5-oxo-2-[4-(trifluoromethoxy)phenyl] -[1,2,3]triazolo[1,5-a]- quinazolinium hydroxide, inner salt.

Prepared by the route of Example 6 using 4-(trifluoromethoxy)aniline (4.7g) to give the title compound (0.535g) as a yellow solid. m.p. >260°C MS APCI (+ve) 363 ((M+H)+) 1H NMR (DMSO-d6) 8 7.63 (2H, d), 7.82 (1H, t), 8.04 (1H, t), 8.32 (4H, m), 12.86 (1H, br, s)

Example 23 4,5-Dihydro-9-fluoro-3-hydroxy-4-methyl-2-[4-(trifluoromethy l)phenyl]- [1,2,3]triazolo[1,5-a]quinolinium hydroxide, inner salt.

(a) 8-Fluoro-4-hydroxy-3-methyl-quinoline-2-carboxylic acid, ethyl ester.

To a solution of 2-fluoroaniline (11.97ml) and magnesium sulphate (lOg) in dichloromethane (100ml) was added diethyl oxalpropionate (25g) and the reaction mixture was refluxed for 48h hours. The solution was concentrated in vacuo and purified by chromatography on silica gel (iso-hexane : diethyl ether/ 10:1). The intermediate was dissolved in diphenyl ether (40ml) and added portionwise to a flask containing diphenyl ether (100ml) at 2500C. After complete addition the reaction mixture was maintained at 250°C for a further 10 minutes. After cooling the reaction mixture was purified by chromatography on silica gel (iso-hexane : diethyl ether/ 10:1 to diethyl ether) to give the subtitle compound (12.2g) as a pale yellow solid.

MS APCI (+ve) 250 ((M+H)+). f!) 8-Fluoro-3-methyl-1,2,3,4-tetrahydroquinoline-2-carboxylic acid A solution of 8-fluoro-4-hydroxy-3-methyl-quinoline-2-carboxylic acid, ethyl ester(11.5g) in phosphorus oxychloride (40ml) was refluxed for 3 hours before being concentrated in vacuo. The residue was quenched with water then basified with sodium hydrogen carbonate solution. The solution was extracted with ethyl acetate, dried over magnesium sulphate and concentrated in vacuo. A solution of the intermediate and 5% platinum on carbon (lug) in ethanol (500ml) was hydrogenated at 5 bar for 14 hours. The reaction

mixture was filtered through Celite then concentrated in vacuo. The residue was dissolved in ethanol (200ml) and sodium hydroxide (5.54g) in water (100ml) was added. The reaction mixture was stirred for 1 hour then hydrochloric acid (200ml - 2M) was added.

The solution was extracted with ethyl acetate (twice), dried over magnesium sulphate and concentrated in vacuo to give the subtitle compound (10.1 3g) as a brown solid.

(c) 4,5-Dihydro-9-fluoro-3-hydroxy-4-methyl-2-[4-(trifluoromethy l)phenyl] [1,2,3]triazolo[1,5-a]quinolinium hydroxide, inner salt.

Prepared by the route of Example 3 using 8-fluoro-3-methyl- 1 ,2,3,4-tetrahydroquinoline-2- carboxylic acid (5g) and 4-(trifluoromethyl)aniline (3.85g) to give the title compound (2.28g) as a yellow solid. m.p. 210-212"C MS APCI (+ve) 364 ((M+H)+) 1H NMR (CDCl3) 6 1.41 (3H, d), 2.89 (1H, d,d), 3.20 (1H, d,d), 3.47 (1H, sextet), 7.23 (2H, m), 7.40 (1H, m) Example 24 4,5-Dihydro-3-hydroxy-5-oxo-2- [4-(trifiuoromethyl)phenyl] -4-(2,2,2-trifluoroethyl)- [1,2,3]triazolo[1,5-a]quinazolinium hydroxide, inner salt.

To a solution of 4,5-dihydro-3-hydroxy-5-oxo-2- [4-(trifluoromethyl)phenyl] - [1,2,3]triazolo[1,5-a]quinazolinium hydroxide, inner salt (Example 6) (lug) and sodium hydride (0.069g - 60% dispersion in mineral oil) in dimethylformamide (25ml) was added

trifluoroethyl triflate (0.4mg) in dimethylformamide (1 ml) and the reaction mixture was stirred overnight. The solution was quenched with sodium hydrogen carbonate solution, filtered and dried in vacuo. Purification by chromatography on silica gel (dichloromethane methanol/ 100:1) followed by recrystallisation gave the title compound (0.33g) as a pale yellow solid. m.p. 243-244°C MS APCI (+ve) 429 ((M+H)+) 1H NMR (CDCl3) 8 5.41 (2H, q), 7.80 (3H, m), 7.99 (1H, t), 8.35 (1H, d), 8.42 (2H, d), 8.50 (1H, d) Example 25 4,5-Dihydro-3-hydroxy-5-oxo-4-methyl-2-[4-(trifluoromethoxy) phenyl]- [1,2,3]triazolo[1,5-a]quinazolinium hydroxide, inner salt.

Prepared by the route of Example 13 using 4,5-dihydro-3-hydroxy-5-oxo-2-[4- (trifluoromethoxy)phenyl]-[ 1,2,3]triazolo[l ,5-a]quinazolinium hydroxide, inner salt (Example 22) (0.45g) to give the title compound (0.26g) as a yellow solid. m.p. 234-235°C MS APCI (+ve) 377 ((M+H)+) 1H NMR (CDCl3) 6 4.05 (3H, s), 7.39 (2H, d), 7.76 (1H, t), 7.92 (1H, t), 8.27 (3H, m), 8.47 (1H, d)

Example 26 2-(6-Chloro-3-pyridinyl)-4,5-dihydro-9-fluoro-3-hydroxy4meth yl [1,2,3]triazolo[1 ,5- a]quinolinium hydroxide, inner salt.

Prepared by the route of Example 3 using 8-fluoro-3-methyl-1,2,3,4-tetrahydroquinoline-2- carboxylic acid (Example 23b) (5g) and 5-amino-2-chloropyridine (2.67g) to give the title compound (1.2g) as a yellow solid. m.p. 205-207°C MS APCI (+ve) 331 ((M+H)+) 1H NMR (CDCl3) 8 1.42 (3H, s), 2.88 (1H, d,d), 3.19 (1H, d,d), 3.45 (1H, sextet), 7.19 (1H, d), 7.25 (1H, m), 7.40 (1H, m), 7.48 (1H, d), 8.65 (1H, d,d), 9.25 (1H, d) Example 27 2-(6-Chloro-3-pyridinyl)-9-fluoro-3-hydroxy-4-methyl-[1,2,3] triazolo[1,5-a]- quinolinium hydroxide, inner salt.

Prepared by the route of Example 17 using 2-(6-chloro-3-pyridinyl)-4,5-dihydro-9-fluoro- 3-hydroxy-4-methyl- [1 ,2,3]triazolo [1 ,5-a]quinolinium hydroxide, inner salt (Example 26) (1g) to give the title compound (0.262g) as a tan solid. m.p. >260°C MS APCI (+ve) 329 ((M+H)+) 1H NMR (CDCl3) 6 2.77 (1H, s), 6.69 (1H, s), 7.37 (1H, m), 7.55 (3H, m), 8.70 (1H, d,d), 9.36 (1H, d) Example 28 9-Fluoro-3-hydroxy-4-methyl-2-[4-(trifluoromethyl)phenyl]-[1 ,2,3]triazolo[1,5-a]- quinolinium hydroxide, inner salt.

Prepared by the route of Example 17 using 4,5-dihydro-9-fluoro-3-hydroxy-4-methyl-2-[4- (trifluoromethyl)phenyl]-[1,2,3]triazolo[1,5-a]quinolinium hydroxide, inner salt (Example 23) (1. lg) to give the title compound (0.470g) as a yellow solid. m.p. 216-218°C MS APCI (+ve) 362 ((M+H)+) 1H NMR (CDCl3) 6 2.78 (3H, s), 6.93 (1H, s), 7.35 (1H, m), 7.47 (1H, d), 7.55 (1H, m), 7.79 (2H, d), 8.50 (2H, d)

Example 29 4,5-Dihydro-2-(4-fluorophenyl)-3-hydroxy-[1,2,3]triazolo[1,5 -a]quinolinium hydroxide, inner salt.

Prepared by the route of Example 3 using 1,2,3,4-tetrahydroquinoline-2-carboxylic acid (6g) and 4-fluoroaniline (3.72g) to give the title compound (4.8g) as a yellow solid. m.p. 144-146°C MS APCI (+ve) 282 ((M+H)+) 1H NMR (CDC13) 87.20 (2H, m), 7.40 (3H, m), 7.80 (1H, m), 8.17 (2H, m) Example 30 5-Bromo-3-hydroxy-2-[4-(trifluoromethyl)phenyl] -[1,2,3]triazolo[1 ,5-a]quinolinium hydroxide, inner salt.

To a solution of 3-hydroxy-2-[4-(trifluoromethyl)phenyl]-[ 1,2,3]triazolo[l ,5-a]quinoiinium hydroxide, inner salt (Example 9) (lg) in dichloromethane (100ml) was added pyridine (0.25ml) then bromine (0.48ml) and stirred for 1 hour. The reaction mixture was partitioned between ethyl acetate and sodium hydrogen carbonate solution. The organic layer was separated, dried over magnesium sulphate and concentrated in vacuo.

Purification by chromatography on silica gel (dichloromethane: ethyl acetate/ 8:1 then ethyl acetate) followed by a diethyl ether wash gave the title compound (560mg) as a yellow solid. m.p. 187-188°C MS APCI (+ve) 408, 410 ((M+H)+).

1H NMR (CDCl3) 6 7.80 (4H, m), 7.99 (1H, s), 8.21 (1H, m), 8.47 (2H, d), 8.57 (1H, m). Example 31 4,5-Dihydro-3-hydroxy-2-(4-methylphenyl)-[1,2,3]triazolo[1,5 -a]quinolinium hydroxide, inner salt.

Prepared by the route of Example 3 using 1,2,3,4-tetrahydroquinoline-2-carboxylic acid (6g) and 4-methylaniline (3.63g) to give the title compound (1.8g) as a pink solid. m.p. 127-129°C MS APCI (+ve) 278 ((M+H)+).

1H NMR (CDC13) 6 2.41 (3H, s), 3.06 (4H, s), 7.31 (2H, d), 7.41 (3H, m), 8.02 (3H, m). Example 32 5-Bromo-9-fluoro-3-hydroxy-2-[4-(trifluoromethyl)phenyl]-[1, 2,3]triazolo[1,5- a]quinolinium hydroxide, inner salt.

Prepared by the route of Example 30 using 9-fluoro-3-hydroxy-2-[4- (trifluoromethyl)phenyl]- [1,2,3]triazolo[l ,5-a]quinolinium hydroxide, inner salt (Example 12) (0.3g) to give the title compound (0.15g) as a yellow solid. m.p. 199-201"C MS APCI (+ve) 426, 428 ((M+H)+) lH NMR (CDC13) 6 7.56 (1H, m), 7.73 (1H, m), 7.81 (2H, d), 8.03 (2H, m), 8.48 (2H, d) Example 33 2-(4-Fluorophenyl)-3-hydroxy-[1,2,3]triazolo[1,5-a]quinolini um hydroxide, inner salt.

Prepared by the route of Example 9 using 4,5-dihydro-2-(4-fluorophenyl)-3-hydroxy- [1,2,3]triazolo[1,5-a]quinolinium hydroxide, inner salt (Example 29) (lg) to give the title compound (0.615g) as a yellow solid.

m.p. 184-186°C MS APCI (+ve) 280 ((M+H)+) lH NMR (CDCl3) 6 7.26 (3H, m), 7.70 (3H, m), 7.83 (1H, m), 8.26 (2H, m), 8.53 (1H, m) Example 34 3-Hydroxy-2-(4-methylphenyl)-[1,2,3]triazolo[1,5-a]quinolini um hydroxide, inner salt.

Prepared by the route of Example 9 using 4,5-dihydro-3-hydroxy-2-(4-methylphenyl)- [1,2,3]triazolo[1,5-a]quinolinium hydroxide, inner salt (Example 31) (1.3g) to give the title compound (0.74g) as a yellow solid. m.p. 183-185°C MS APCI (+ve) 276 ((M+H)+) lH NMR (CDCl3) 6 2.43 (3H, s), 7.24 (1H, d), 7.35 (2H, d), 7.68 (3H, m), 7.81 (1H, m), 8.12 (2H, m), 8.53 (1H, m)

Example 35 4,5-Dihydro-3-hydroxy-2-[4-(trifluoromethoxy)phenyl]-[1,2,3] triazolo[1,5-a]- quinolinium hydroxide, inner salt.

Prepared by the route of Example 3 using 1,2,3,4-tetrahydroquinoline-2-carboxylic acid (12g) and (4-trifluoromethoxy)aniline (12.01g) to give the title compound (8.44g) as a cream solid. m.p. 163-165"C MS APCI (+ve) 348 ((M+H)+) lH NMR (CDC13) 6 3.07 (4H, s), 7.40 (SH, m), 8.00 (1H, m), 8.27 (2H, m) Example 36 4,5-Dihydro-3-hydroxy-2-phenyl-[1,2,3]triazolo[1,5-a]quinoli nium hydroxide, inner salt.

Prepared by the route of Example 3 using 1 ,2,3,4-tetrahydroquinoline-2-carboxylic acid (12g) and aniline (6.31g) to give the title compound (4.9g) as a brown solid. m.p. 145-146°C MS APCI (+ve) 264 ((M+H)+)

1H NMR (CDC13) 6 3.07 (4H, s), 7.40 (4H, m), 7.52 (2H, m), 8.62 (1H, m), 8.17 (2H, m) Example 37 3-Hydroxy-2-[4-(trifiuoromethoxy)phenyl)-[1,2,3]triazolo[1 ,5-a]quinolinium hydroxide, inner salt.

Prepared by the route of Example 9 using 4,5-dihydro-3-hydroxy-2-[4- (trifluoromethoxy)phenyl)- [1,2,3]triazolo[1,5 -a] quinolinium hydroxide, inner salt (Example 35) (Sg) to give the title compound (4.3g) as a yellow solid. m.p. 155-156°C MS APCI (+ve) 346 ((M+H)+) lH NMR (CDCl3) 8 7.28 (1H, m), 7.40 (2H, m), 7.70 (3H, m), 7.84 (1H, m), 8.36 (2H, m), 8.54 (1H, m) Example 38 5-Bromo-2-(4-fluorophenyl)-3-hydroxy-[1,2,3]triazolo[1,5-a]q uinolinium hydroxide, inner salt.

Prepared by the route of Example 30 using 2-(4-fluorophenyl)-3-hydroxy- [1,2,3]triazolo[l ,5-a]quinolinium hydroxide, inner salt (Example 33) (3g) to give the title compound (1g) as a yellow solid. m.p. > 250°C MS APCI (+ve) 358, 360 ((M+H)+) 1H NMR (CDCl3) 6 7.23 (2H, m), 7.78 (2H, m), 7.98 (1H, s), 8.20 (3H, m), 8.53 (1H, m) Example 39 3-Hydroxy-2-phenyl-[1,2,3]triazolo[1,5-a]quinolinium hydroxide, inner salt.

Prepared by the route of Example 9 using 4,5-dihydro-3-hydroxy-2-phenyl- [1,2,3]triazolo[l ,5-a]quinolinium hydroxide, inner salt (Example 36) (4.1g) to give the title compound (1.7g) as a yellow solid. m.p. 153-155°C MS APCI (+ve) 262 ((M+H)+) lH NMR (CDCl3) 3 7.25 (1H, m), 7.4 (1H, m), 7.53 (2H, m), 7.70 (3H, m), 7.82 (1H, m), 8.26 (2H, m), 8.54 (1H, d)

Example 40 5-Bromo-3-hydroxy-2-phenyl-[1,2,3]triazolo[1,5-a]quinolinium hydroxide, inner salt.

Prepared by the route of Example 30 using 3-hydroxy-2-phenyl-[ 1,2,3]triazolo[1,5- a]quinolinium hydroxide, inner salt (Example 39) (1.2g) to give the title compound (1g) as a yellow solid. m.p. 246-249°C MS APCI (+ve) 340, 342 ((M+H)+) lH NMR (CDCl3) 57.44 (1H, m), 7.58 (2H, m), 7.77 (2H, m), 7.99 (1H, s), 8.19 (3H, m), 8.55 (lH, m) Example 41 5-B romo-3-hydroxy-2-[4-(trifluoromethoxy)phenyl] -[1,2,3]triazolo[1 ,5-a]quinolinium hydroxide, inner salt.

Prepared by the route of Example 30 using 3-hydroxy-2-[4-(trifluoromethoxy)phenyl]- [1,2,3]triazolo[1,5-a]quinolinium hydroxide, inner salt (Example 37) (2.3g) to give the title compound (1g) as a yellow solid.

m.p. 202-204°C MS APCI (+ve) 424, 426 ((M+H)+) lH NMR (CDCl3) 8 7.40 (2H, d), 7.78 (2H, m), 7.98 (1H, s), 8.21 (1H, m), 8.33 (2H, m), 8.55 (1H, m) Example 42 2-(6-Chloro-3-pyridinyl)-4,5-dihydro-3-hydroxy-[1,2,3]triazo lo[1,5-a]quinolinium hydroxide, inner salt.

Prepared by the route of Example 3 using 1,2,3,4-tetrahydroquinoline-2-carboxylic acid (8.3g) and 5-amino-2-chloropyridine (6g) to give the title compound (6.12g) as a tan solid.

MS APCI (+ve) 299 ((M+H)+) lH NMR (CDCl3) 8 3.07 (4H, s), 7.44 (4H, m), 8.01 (1H, m), 8.70 (1H, d,d), 9.20 (1H, d)

Example 43 3-Hydroxy-5-(4-morpholinyl)-2-[4-(trifluoromethyl)phenyl]-[1 ,2,3]triazolo[1,5-a]- quinolinium hydroxide, inner salt.

A solution of 5-bromo-3-hydroxy-2- [4-(trifluoromethyl)phenyl] - [1,2,3]triazolo[1,5- a]quinolinium hydroxide, inner salt (Example 30) (816mg), tris(dibenzylideneacetone)dipalladium (10mg), (R)-(+)-2,2-bis(diphenylphosphino)- 1,1 - binaphthyl (20mg), morpholine (0.6ml) and sodium tertiary butoxide (0.27g) in toluene (18ml) was heated at 1200C overnight. Purification by chromatography on silica gel (dichloromethane : ethyl acetate/ 1:1) followed by a diethyl ether wash gave the title compound (480mg) as a yellow solid. m.p. >250°C MS APCI (+ve) 415 ((M+H)+). lH NMR (CDC13) 3.12 (4H, t), 3.99 (4H, t), 7.22 (1H, s), 7.75 (4H, m), 8.15 (1H, m), 8.50 (2H, d), 8.58 (1H, m).

Example 44 3-Hydroxy-5-(4-morpholinyl)-2-[4-(trifluoromethoxy)phenyl]-[ 1,2,3]triazolo[1,5-a]- quinolinium hydroxide, inner salt.

Prepared by the route of Example 43 using 5-bromo-3-hydroxy-2-[4- (trifluoromethoxy)phenyl]-[ 1,2,3]triazolo[l ,5-a]quinolinium hydroxide, inner salt (Example 41) (1.4g) to give the title compound (0.602g) as a yellow solid. m.p. 231-232"C MS APCI (+ve) 431 ((M+H)+) lH NMR (CDCl3) 6 3.12 (4H, t), 3.99 (4H, t), 7.22 (1H, s), 7.39 (2H, d), 7.73 (2H, m), 8.1 (1H, m), 8.35 (2H, m), 8.56 (1H, m) Example 45 2-(6-Chloro-3-pyridinyl)-3-hydroxy-[1,2,3]triazolo[1,5-a]qui nolinium hydroxide, inner salt.

Prepared by the route of Example 20 using 4,5-dihydro-2-(6-chloro-3-pyridinyl)-3- hydroxy-[1,2,3]triazolo[l,S-a]quinolinium hydroxide, inner salt (Example 42) (5g) to give the title compound (2g) as a yellow solid. m.p. 229-230°C MS APCI (+ve) 297, 299 ((M+H)+) 1H NMR (CDCl3) # 7.32 (1H, d), 7.51 (1H, d), 7.74 (3H, m), 7.85 (1H, m), 8.55 (1H, d), 8.78 (1H, d,d), 9.31 (1H, d) Example 46 2-(4-Chlorophenyl)-3-hydroxy-[1,2,3]triazolo[1,5-a]quinolini um hydroxide, inner salt.

Prepared by the route of Example 20 using 4,5-dihydro-2-(4-chlorophenyl)-3-hydroxy- [1,2,3]triazolo[1,5-a]quinolinium hydroxide, inner salt (Example 4) (12.7g) to give the title compound (4.8g) as a yellow solid. m.p. 163-165"C MS APCI (+ve) 296, 298 ((M+H)+) lH NMR (CDCl3) 6 7.27 (1H, m), 7.51 (2H, m), 7.71 (3H, m), 7.83 (1H, m), 8.28 (2H, m), 8.53 (1H, m) Example 47 5-Bromo-2-(4-chlorophenyl)-3-hydroxy-[1,2,3]triazolo[1,5-a]q uinolinium hydroxide, inner salt.

Prepared by the route of Example 30 using 2-(4-chlorophenyl)-3-hydroxy [1,2,3]triazolo[1,5-a]quinolinium hydroxide, inner salt (Example 46) (3.8g) to give the title compound (3.67g) as a yellow solid. m.p. 238-240°C MS APCI (+ve) 374, 376, 378 ((M+H)+) lH NMR (CDC13) 3 7.51 (2H, m), 7.78 (2H, m), 7.99 (1H, s), 8.22 (3H, m), 8.55 (1H, m) Example 48 3-Hydroxy-4-oxo-2- [4- (trifluoromethyl)phenyl] -4,5-dihydro-[l ,2,3]triazolo[1,5 -a]- quinoxalinium hydroxide, inner salt.

(a) Methyl 2-(carboxymethylamino)benzoate

To a stirred solution of methylanthranilate (30g) in xylene (300ml) was added bromoacetic acid (27.8g) and the reaction mixture was refluxed for 14 hour. The solution was cooled then partitioned between aqueous sodium bicarbonate solution and diethyl ether. The aqueous layer was acidified to pH4 with hydrochloric acid and extracted with ethyl acetate.

The extracts were dried over magnesium sulphate and concentrated in vacuo to give the subtitle compound (21.7g).

MS APCI (-ve) 208 ((M-H)+).

(b) 4-Hydroxy-1-(2-methoxycarbonylphenyl)-3-[4-(trifluoromethyl) phenyl]- [1,2,3]triazolium hydroxide, inner salt To a stirred solution of 4-(trifluoromethyl)aniline (4.2g)in a mixture of water (50ml), tetrahydrofuran (20ml) and concentrated hydrochloric acid (lOml) at O to -50C, was added portionwise a solution of sodium nitrite (1.9lug) in water (20ml). The solution was stirred 15 minutes at O to -50C and was then added portionwise to a solution of methyl 2- (carboxymethylamino)benzoate (5g) in pyridine (50ml) and water (lOml) at O to -50C. The solution was stirred for 1 hour at O OC and then for lhour at 0- 100C. The mixture was diluted with ethyl acetate and the organics separated, dried over magnesium sulphate and concentrated in vacuo to ca 30ml volume. To the residue was added acetic anhydride (1 Oml) and the solution was stirred for 1 hour. The reaction mixture was concentrated in vacuo, azeotroping twice with toluene. The product was chromatographed on silica (ethyl acetate then ethyl acetate:ethanol/10: 1). Crystallization from ethyl acetate/isohexane gave the subtitle compound (1.50g) as a colourless solid.

MS APCI (+ve) 364 ((M+H)+). lH NMR (DMSO-d6) 6 8.30 (2H, d), 8.05 (1H, d), 8.0-7.8 (5H, m), 7.72 (1H, s), 3.73 (3H, s).

(c) 1-(2-Carboxyphenyl)-4-hydroxy-3-[4-(trifluoromethyl)phenyl]- [1,2,3]triazolium hydroxide, inner salt.

To a stirred solution of 4-hydroxy-1-(2-methoxycarbonylphenyl)-3-[4- (trifluoromethyl)phenyl] - [1 ,2,3]triazolium hydroxide, inner salt (4.55g) in tetrahydrofuran (SOml) and methanol (lSml) was added a solution of sodium hydroxide (0.60g) in water (lSml). After 30min. the solution was acidified with aqueous potassium hydrogen sulphate solution and extracted with ethyl acetate. The organics were concentrated in vacuo and azeotroped to dryness with toluene to give the subtitle compound (3.8g) as a colourless solid.

MS APCI (+ve) 350 ((M+H)+). lH NMR (DMSO-d6) 8 8.31 (2H, d), 8.01 (1H, d), 7.96(2H, d), 7.88-7.77 (3H, m), 7.66 (1H, s). <BR> <BR> <BR> <BR> <BR> <P>(dl 3-Hydroxy-4-oxo-2-[4-(trifluoromethyl)phenyl]- 4,5-dihydro-[1,2,3]triazolo[1,5-a] quinoxalinium hydroxide, inner salt.

To a stirred solution of 1-(2-carboxyphenyl)-4-hydroxy-3-[4-(trifluoromethyl)phenyl]- [1 ,2,3]triazolium hydroxide, inner salt (1.2g) in anhydrous toluene (40ml) and triethylamine (1.2ml) was added diphenylphosphorylazide (1.2ml) and the mixture stirred at room temperature for 14h. The mixture was then heated at 750C for 20 min.

Dichloromethane (40ml) was added and the mixture allowed to cool. The precipitate was filtered and washed with dichloromethane followed by ethyl acetate then diethyl ether, and dried in vacuo to give the title compound (1 .05g) as a colourless solid.

MS APCI (+ve) 347 ((M+H)+). lH NMR (DMSO-d6) 6 11.68 (1H,s), 8.50 (2H, d), 8.25 (1H, dd), 8.01(2H, d), 7.64 (1H, m), 7.37 (2H, m).

Example 49 3-Hydroxy-2- [4-(trifluoromethyl)phenyl] -[1,2,3]triazolo[1,5-a]quinoxalinium hydroxide, inner salt.

(a) 4-Chloro-3-hydroxy-2-[4-(trifluoromethyl)phenyl] - [1 ,2,3]triazolo[1 ,S-a]- quinoxalinium hydroxide, inner salt A solution of 3-hydroxy-4-oxo-2- [4-(trifluoromethyl)phenyl]- 4,5-dihydro- [1,2 ,3]triazolo [1 ,5-a]quinoxalinium hydroxide, inner salt (Example 48) (2.17g) in phosphorus oxychloride (30ml) was refluxed for 2 hours before being concentrated in vacuo. The residue was quenched with aqueous sodium bicarbonate solution and extracted with dichloromethane, dried over magnesium sulphate and concentrated in vacuo to give the subtitle compound (1.80g) (b) 3-Hydroxy-2- [4-(trifluoromethyl)phenyl] -4,5-dihydro- [1,2,3]triazolo[l ,5- a]quinoxalinium hydroxide, inner salt.

To a stirred solution of 4-chloro-3-hydroxy-2-[4-(trifluoromethyl)phenyl]- [1,2,3]triazolo[l ,5-a]quinoxalinium hydroxide, inner salt (1.3g) in ethanol (100ml) was added portionwise sodium borohydride (1.35g) over a period of lh. Saturated aqueous ammonium chloride solution was added and the mixture concentrated in vacuo. The residue was partitioned between dichloromethane and saturated aqueous ammonium chloride solution. The organics were dried over magnesium sulphate, concentrated in vacuo and chromatographed on silica to give the subtitle compound.

MS APCI (+ve) 333 ((M+H)+).

(c) 3-Hydroxy-2-[4-(trifluoromethyl)phenyl]-[1,2,3]triazolo[1,5- a]quinoxalinium hydroxide, inner salt.

3-Hydroxy-2-[4-(trifluoromethyl)phenyl]-4,5-dihydro-[1,2, 3]triazolo[1,5-a]quinoxalinium hydroxide, inner salt (20mg) was allowed to stand as a chloroform solution in the air for 48h. The solution was concentrated in vacuo and recrystallized from ethyl acetate/isohexane to give the title compound as a colourless solid (5mg).

MS APCI (+ve) 331 ((M+H)+). lH NMR (CDCl3) 89.10 (lH,s), 8.44 (3H, m), 8.13 (1H, d), 7.85 (3H, m), 7.76 (lH, t).

Example 50 4-Azetidinyl-3-hydroxy-2-[4-(trifluoromethyl)phenyl]-[1,2,3] triazolo[1,5-a]- quinoxalinium hydroxide, inner salt.

To a stirred solution of 4-chloro-3-hydroxy-2-[4-(trifluoromethyl)phenyl]- [1,2,3]triazolo[l,5-a]quinoxalinium hydroxide, inner salt (Example 49a) (0.5g) in dichloromethane (lOml) was added azetidine (1 ml). The mixture was stirred for lh at room temperature then concentrated in vacuo. Chromatography on silica followed by crystallization from ethyl acetate/isohexane gave the title compound as fine needles (100mg).

MS APCI (+ve) 386 ((M+H)+). lH NMR (DMSO-d6) 6 8.36 (2H, d), 8.19 (1H, dd), 7.79 (2H, d), 7.64 (1H, d), 7.56 (1H, m), 7.27 (1H, m), 4.55 (4H, m), 2.45 (2H, quintet).

Example 51 3-Hydroxy-4-methyl-5-nitro-2-[4-(trifluoromethyl)phenyl]-[1, 2,3]triazolo[1,5-a]- quinolinium hydroxide, inner salt.

To a stirred solution of 3-hydroxy-4-methyl-2- [4-(trifluoromethyl)phenyl]- [1,2,3]triazolo[l,S-a]quinolinium hydroxide, inner salt (Example 19) (1.0g) in dichloromethane (SOml) was added a solution of nitronium tetrafluoroborate in sulfolane dropwise until conversion was complete by thin layer chromatographic analysis. The mixture was poured into saturated aqueous sodium bicarbonate solution and extracted with dichloromethane. The extracts were dried over magnesium sulphate and concentrated in vacuo. Recrystallization from ethyl acetate/isohexane gave the title compound as yellow needles (0.72g).

MS APCI (+ve) 389 ((M+H)+). lH NMR (CDC13) 6 8.57 (1H, m), 8.43 (2H, d), 7.80 (SH, m), 3.08 (3H, s).

Example 52 2-(4-Chlorophenyl)-3-hydroxy-4-methyl-5-nitro-[1,2,3]triazol o[ 1,5-a]quinolinium hydroxide, inner salt.

To a stirred solution of 2-(4-chlorophenyl)-3-hydroxy-4-methyl-[1,2,3]triazolo[1,5- a]quinolinium hydroxide, inner salt (0.20g) in dichloromethane (15ml) was added a solution of nitronium tetrafluoroborate in sulfolane dropwise until conversion was complete by thin layer chromatographic analysis. The mixture was poured into saturated aqueous sodium bicarbonate solution and extracted with dichloromethane. The extracts were dried over magnesium sulphate and concentrated in vacuo. Chromatography on silica (isohexane: ethyl acetate/9: 1) gave the title compound as a solid (0.139g).

MS APCI (+ve) 355 ((M+H)+).

1H NMR (CDC13) 8 8.58 (1H, m), 8.2 (2H, m), 7.82-7.74 (3H, m), 7.55-7.48(2H,m), 2.84 (3H, s).

Example 53 3-Hydroxy-4-(1-methylethyl)-2-[4-(trifluoromethyl)phenyl]-[1 ,2,3]triazolo[1,5-a]- quinoxalinium hydroxide, inner salt.

To a stirred suspension of 3-hydroxy-4-oxo-2- [4-(trifluoromethyl)phenyl]- 4,5-dihydro- [1,2,3]triazolo[l ,5-a]quinoxalinium hydroxide, inner salt (Example 48) (0.30g) in toluene (25ml) at 80°C was added a solution of isopropylmagnesium chloride (2M in diethyl ether, 2.5ml). After lOmin the reaction was quenched with water and the product extracted with ethyl acetate and concentrated in vacuo. Chromatography on silica (diethyl ether: isohexane, 1:1) and washing with ether gave the title compound (0.05g) as a yellow powder.

MS APCI (+ve) 373 ((M+H)+).

1H NMR (DMSO-d6) 8 8.43 (2H, d), 8.40 (1H, d), 8.02 (1H, d), 7.81 (2H, d), 7.76 (1H, t), 7.64(1H, t), 4.10 (1H, m), 1.43 (6H, d).

Example 54 3-Hydroxy-4-methyl-2-[4-(trifluoromethyl)phenyl]-[1,2,3]tria zolo[1,5-a]- quinoxalinium hydroxide, inner salt.

To a stirred suspension of 3-hydroxy-4-oxo-2-[4-(trifluoromethyl)phenyl]-4,5-dihydro- [1,2,3]triazolo[l ,5-a]quinoxalinium hydroxide, inner salt (Example 48) (0.467g) in toluene (20ml) at 80"C was added a solution of methylmagnesium chloride (3M in tetrahydrofuran, 2ml). After lOmin the reaction was quenched with water and the product extracted with ethyl acetate and concentrated in vacua. Chromatography on silica (diethyl ether: isohexane, 3:1) gave the title compound (0.05g) as a yellow powder.

MS APCI (+ve) 345 ((M+H)+).

1H NMR (DMSO-d6) 6 8.46 (3H, d), 8.02 (2H, d), 7.98 (1H, d), 7.86 (1H, t), 7.71 (1H, t), 2.80 (3H, s).

Example 55 2-(4- Chlorophenyl)-3-hydroxy-4-oxo-4,5-dihydro-[1,2,3]triazolo[1, 5-a]quinoxalinium hydroxide, inner salt Prepared as for Example 48 employing 4-chloroaniline and methyl 2- (carboxymethylamino)benzoate to give the title compound as a colourless solid.

MS APCI (+ve) 313/315 ((M+H)+). lH NMR (DMSO-d6) 8 8.22-8.14 (3H, m), 7.63-7.55 (3H, m), 7.41 (1H, d), 7.33 (1H, dd).

Example 56 2-(4-Chlorophenyl)-3-hydroxy-4-(1-methylethyl)-[1,2,3]triazo lo[1,5-a]quinoxalinium hydroxide, inner salt.

To a stirred suspension of 2-(4-chlorophenyl)-3-hydroxy-4-oxo-4,5-dihydro- [1,2,3]triazolo[l ,5-a]quinoxalinium hydroxide, inner salt (Example 55) (0.30g) in toluene (25ml) at 80°C was added a solution of isopropylmagnesium chloride (2M in diethyl ether, 2.5ml). After lOmin the reaction was quenched with water and the product extracted with ethyl acetate and concentrated in vacuo. Chromatography on silica (diethyl ether: isohexane, 1:1) gave the title compound (0.05g) as a yellow solid.

MS APCI (+ve) 339/341 ((M+H)+).

1H NMR (DMSO-d6) 6 8.43 (1H, d), 8.22 (2H, d), 8.00 (1H, d), 7.84 (1H, t), 7.76 (1H, t), 7.74 (2H, d), 3.93 (1H, m), 1.37 (6H, d).

Example 57 2-(4-Chlorophenyl)-3-hydroxy-4-methyl-[1,2,3]triazolo[1,5-a] quinoxalinium hydroxide, inner salt.

To a stirred suspension of 2-(4-chlorophenyl)-3-hydroxy-4-oxo-4,5-dihydro- [1,2,3]triazolo[1,5-a]quinoxalinium hydroxide, inner salt (Example 55) (0.Slg) in toluene (20ml) at 80"C was added a solution of methylmagnesium chloride (3M in tetrahydrofuran, 2.2ml). After lOmin the reaction was quenched with water and the product extracted with ethyl acetate and concentrated in vacuo. Chromatography on silica (diethyl ether: isohexane, 3:1) and recrystallization from ethyl acetate gave the title compound (0.05g) as a yellow powder.

MS APCI (+ve) 311/313 ((M+H)+).

Example 58 3-Hydroxy-5-methyl-4-oxo-2-[4-(trifluoromethyl)phenyl]- 4,5-dihydro- [1,2,3]triazolo[1,5-a]quinoxalinium hydroxide, inner salt.

To a stirred solution of 3-hydroxy-4-oxo-2-[4-(trifluoromethyl)phenyl]- 4,5-dihydro- [1 ,2,3]triazolo[ 1 ,S-a]quinoxalinium hydroxide, inner salt (Example 48) (0.50g) in dimethylformamide (20ml) was added methyl iodide (0.22ml) followed by sodium hydride (0.35g, 60% dispersion in mineral oil). After 7h the reaction was carefully quenched with water (100ml). The product was filtered and washed with water, then acetone then diethyl ether. Recrystallization from methanol gave the title compound (0.23g). m.p. <350°C MS APCI (+ve) 361 ((M+H)+).

lH NMR (CDCl3) 6 3.67 (3H, s), 7.40(1H, m), 7.43 (1H, d), 7.69 (lH, m), 7.81 (2H, d), 8.32 (1H, d), 8.39 (2H, d). Example 59 2-(4-Fluorophenyl)-3-hydroxy-5-nitro-[1,2,3]triazolo[1,5-a]q uinolinium hydroxide, inner salt.

Prepared by the route of Example 51 using 2-(4-fluorophenyl)-3-hydroxy- [1,2,3]triazolo[l ,5-a]quinolinium hydroxide, inner salt (Example 33) (1.7g) to give, after recrystallization from ethyl acetate, the title compound (1.58g) as an orange solid. m.p. > 250°C MS APCI (+ve) 325 ((M+H)+) lH NMR (CDCl3) # 7.25 (2H, m), 7.86 (2H, m), 8.18 (2H, m), 8.60 (1H, m), 8.74 (1H, s), 8.89 (1H, m) Example 60 5-Amino-2-(4-fluorophenyl)-3-hydroxy-[1 ,2,3]triazolo[1,5-a]quinolinium hydroxide, inner salt.

A solution of 2-(4-fluorophenyl)-3-hydroxy-5-nitro-[1,2,3]triazolo[1,5-a]q uinolinium hydroxide, inner salt (Example 59) (lg) in ethanol was hydrogenated (Sbar) over 10% palladium on charcoal. Once hydrogen uptake ceased the solution was filtered and concentrated in vacuo. Chromatography on silica (dichloromethane : methanol/ 10:1) gave the title compound (0.45g) as an orange solid. m.p. > 250°C MS APCI (+ve) 295 ((M+H)+) lH NMR (DMSO-d6) 6 6.33 (2H, s), 6.64 (1H, s), 7.41 (2H, m), 7.80 (1H, t), 7.87 (1H, t), 8.29 (3H, m), 8.51 (lH, d) Example 61 5-Amino-3-hydroxy-4-methyl-2 [4-(trifluoromethyl)phenyl] -[1,2,3]triazolo[1,5-a]- quinolinium hydroxide, inner salt.

A solution of 3-hydroxy-4-methyl-S-nitro-2- [4-(trifluoromethyl)phenyl] - [1 ,2,3]triazolo [1 ,5-a]quinolinium hydroxide, inner salt (Example S1) (0.60g) in ethanol (lOml) was hydrogenated (4bar) over 10% palladium on charcoal. Once hydrogen uptake ceased the solution was filtered and concentrated in vacuo. Crystallization from ethyl acetate gave the title compound (0.52g) as an orange solid. m.p. > 251-2"C MS APCI (+ve) 359 ((M+H)+) 1H NMR (DMSO-d6) # 2.57 (3H, s), 5.94 (2H, s), 7.80 (2H, m), 7.96 (2H, d), 8.32 (1H, m), 8.53 (1H, m), 8.55 (2H, d).

13CNMR(DMSO-d6)89.25(CH3), 116.S(CH), 125.7 (C), 122.1(C), 121.2 (C), 120.6 (2 X CH), 121.7 (CH), 126.1(2 X CH, q), 128.5 (CH), 128.7 (CH), 129.1 (C), 132.9 (C), 139.6 (C), 153.5 (C).

Example 62 4-Ethyl-3-hydroxy-2-[4-(trifluoromethyl)phenyl]-[1,2,3]triaz olo[1,5-a]quinoxalinium hydroxide, inner salt.

To a stirred suspension of 3-hydroxy-4-oxo-2-[4-(trifluoromethyl)phenyl]- 4,5-dihydro- [1,2,3]triazolo[1,5-a]quinoxalinium hydroxide, inner salt (Example 48) (0.90g) in toluene (lSOml) at 75°C was added a solution of ethylmagnesium chloride (3M in diethyl ether, 3ml). After S min the reaction was quenched with water (3ml) and the product extracted with ethyl acetate and concentrated in vacuo. Chromatography on silica (dichloromethane: diethyl ether , 4:1) followed by recrystallization from ethyl acetate : isohexane gave the title compound (0.109g) as colourless needles. m.p. 181°C MS APCI (+ve) 359 ((M+H)+). lH NMR (CDC13) 6 1.47 (3H, t), 3.33 (2H, q), 7.78 (3H, m), 8.03 (1H, dd), 8.42 (3H, m).

Example 63 3-Hydroxy-4-methyl-2-(3-pyridinyl)-[1,2,3]triazolo[1,5-a]qui noxalinium hydroxide, inner salt (a) [2-(Acetylamino)phenyl]amino acetic acid, lithium salt A solution of 2-nitroacetanilide (SOg) in methanol (1L) was stirred with 10% palladium on charcoal (lOg) under an atmosphere of hydrogen (Sbar). Once hydrogen uptake had ceased a solution of glyoxylic acid monohydrate (26.2g) in water (100ml) was added and the mixture rehydrogenated at Sbar. Once hydrogen uptake had ceased the mixture was filtered rapidly and lithium hydroxide (11.96g) in water (loom) was added. The solution was concentrated to a volume of ca 100ml in vacuo. The subtitle compound was precipitated by addition of acetone and dried in vacuo. lH NMR (DMSO-d6/D20) 82.08 (3H, s), 3.38 (2H, s), 6.55 (2H,m), 7.06 (2H, m).

(b) 1-(2-Acetylamino)phenyl-3-(3-pyridinyl)-4-hydroxy-[1,2,3]tri azolium hydroxide, inner salt.

To a solution of 3-aminopyridine (9.4g) in water (120ml), tetrahydrofuran (60ml) and concentrated hydrochloric acid (30ml) at -50C was added a solution of NaNO2 (7.25g) in water (60ml) dropwise maintaining a temperature of less than 0°C. Once addition was complete the solution was stirred for a further l5min at 0°C then added portionwise to a solution of 2-(acetylamino)phenylamino acetic acid, lithium salt (Example 63a, 21.4g) in pyridine (200ml) at -SC maintaining a temperature of less than 0°C. The mixture was stirred at 0°C for lh before being partitioned between ethyl acetate and water. The organic

layer was collected and dried over magnesium sulfate then concentrated in vacuo until only pyridine remained (ca 30ml volume). To the pyridine solution was added acetic anhydride (25ml) and the solution was allowed to stir for 14h. The reaction mixture was concentrated in vacuo and azeotroped with toluene. Chromatography on silica eluting with 10:1 dichloromethane/methanol followed by recrystallization from dichloromethane: ethyl acetate gave the subtitle compound (5.86g) as colourless crystals. m.p. 1900C MS APCI (+ve) 296 ((M+H)+). lH NMR (DMSO-d6) 8 2.02 (3H, s), 7.40 (1H, t), 7.50 (1H, s). 7.63 (2H, m), 7.71 (1H, d), 8.44 (1H, m), 8.64 (1H, m), 9.25 (1H,m), 9.77 (1H, s).

(c) 3-Hydroxy-4-methyl-2-(3-pyridinyl)-[1,2,3]triazolo[1,5-a]qui noxalinium hydroxide, inner salt To 1 -(2-acetylamino)phenyl-3-(3-pyridinyl)-4-hydroxy-[1,2,3]tria zolium hydroxide, inner salt (5.4g) in toluene (300ml) was added toluenesulphonic acid monohydrate (6.60g) and the mixture was heated with azeotropic removal of water (Dean and Stark conditions) for 12h. The reaction mixture was concentrated in vacuo and partitioned between dichloromethane and water. The organic layer was collected and dried over magnesium sulfate then concentrated in vacuo. Chromatography on silica eluting with 20:1 dichloromethane/methanol followed by recrystallization from ethyl acetate gave the title compound (5.86g) as pale orange crystals. m.p. 209°C MS APCI (+ve) 278((M+H)+). lH NMR (CDC13) 82.97 (3H, s), 7.51 (1H, dd), 7.67 (1H, t). 7.78 (1H, t), 8.00 (1H, d), 8.40 (1H, d), 8.65 (2H, m), 9.42 (lH,d).

Example 64 2-(3,4-Difluorophenyl)-3-hydroxy-4-methyl-[1,2,3]triazolo[1, 5-a]quinoxalinium hydroxide, inner salt (a) 1-(2-Acetylamino)phenyl-3-(3,4-difluorophenyl)-4-hydroxy-[1, 2,3]triazolium hydroxide, inner salt.

To a solution of 3,4-difluoroaniline (12.9g) in water (120ml), tetrahydrofuran (60ml) and concentrated hydrochloric acid (30ml) at -50C was added a solution of NaN9 (7.25g) in water (60ml) dropwise maintaining a temperature of less than 0°C. Once addition was complete the solution was stirred for a further 1 Smin at OOC then added portionwise to a solution of 2-(acetylamino)phenylamino acetic acid, lithium salt (Example 63a, 21.4g) in pyridine (200ml) at -5°C maintaining a temperature of less than 0°C. The mixture was stirred at 0°C for lh before being partitioned between ethyl acetate and water. The organic layer was collected and dried over magnesium sulfate then concentrated in vacuo until only pyridine remained (ca 30ml volume). To the pyridine solution was added acetic anhydride (25ml) and the solution was allowed to stir for 14h. The product was filtered and washed with ethyl acetate. Recrystallization from dichloromethane: methanol gave the subtitle compound (7.05g) as colourless crystals. m.p. 209°C MS APCI (+ve) 331 ((M+H)+). lH NMR (DMSO-d6) 8 2.00 (3H, s), 7.40 (1H, m), 7.48 (1H, s). 7.66 (1H, m), 7.70 (1H, m), 7.88 (1H,d), 7.94 (1H, m), 8.24 (1H, dd.), 9.76 (1H, s).

(b) 2-(3,4-Difluorophenyl)-3-hydroxy-4-methyl-[1,2,3]triazolo[1, 5-a]quinoxalinium hydroxide, inner salt To 1 -(2-acetylamino)phenyl-3-(3 ,4-difluorophenyl)-4-hydroxy-[ 1,2,3]triazolium hydroxide, inner salt (6.5g) in toluene (500ml) was added toluenesulphonic acid monohydrate (4.12g) and the mixture was heated with azeotropic removal of water (Dean and Stark conditions) for 14h. After cooling, suspended solids were dissolved in dichloromethane and the combined organics were washed with aqueous sodium bicarbonate solution. The aqueous was reextracted with dichloromethane and the combined extracts dried over magnesium sulfate then concentrated in vacuo to a volume of ca 300ml to induce crystallization. The product was filtered and recrystallized from ethyl acetate gave the title compound (1.65g) as pale yellow needles. A second crop of product was also obtained (0.73g) m.p. 201°C MS APCI (+ve) 313 ((M+H)+). lH NMR (CDC13) 82.96 (3H, s), 7.35 (1H, dd), 7.66 (1H, m). 7.79 (1H, m), 7.99 (1H, d), 8.06 (1H, m), 8.19 (1H, dd.), 8.37 (lH,d).

Example 65 3-Hydroxy-4-methyl-2-(6-methyl-3-pyridinyl)-[1,2,3]triazolo[ 1,5-a]quinoxalinium hydroxide, inner salt (a) 1-(2-Acetylamino)phenyl-3-(6-methyl-3-pyridinyl)-4-hydroxy-[ 1,2,3]triazolium hydroxide, inner salt.

To a solution of 3-amino-6-methylpyridine (S.SSg) in water (100ml), tetrahydrofuran (40ml) and concentrated HCI (20ml) at -50C was added a solution of NaNO2 (3.54g) in water (loll) dropwise maintaining a temperature of less than 0°C. After full addition the solution was stirred for lSmin at 0°C then added portionwise to a solution of 2- (acetylamino)phenylamino acetic acid, lithium salt (Example 63a, lOg) in pyridine (l00ml) at 0°C maintaining a temperature of less than 0°C. After full addition the mixture was stirred at OOC for lh before being partitioned between ethyl acetate and water. The organic layer was collected and dried over magnesium sulfate then was concentrated in vacuo until only pyridine remained. To the pyridine at 0°C was added acetic anhydride (20ml) and the solution was allowed to stir for 72h. The reaction mixture was concentrated in vacuo azeotroping with toluene and chromatographed (silica) eluting with 10:1 dichloromethane/methanol to yield SSOmg of the subtitled compound. <BR> <BR> <BR> <BR> <BR> <BR> <P>(b) 3-Hydroxy-4-methyl-2-(6-methyl-3-pyridinyl)-[1,2,3]triazolo[ 1,5-a]quinoxalinium hydroxide, inner salt To 1 -(2-acetylamino)phenyl-3-(6-methyl-3-pyridinyl)-4-hydroxy- [1 ,2,3 ]triazolium hydroxide, inner salt (SSOmg) in toluene (SOml) was added toluenesulphonic acid (372mg) and the mixture was heated under Dean and Stark conditions for 2h. The reaction mixture was concentrated in vacuo and partitioned between dichloromethane and water. The organic layer was collected, dried over magnesium sulfate and concentrated in vacuo.

Normal phase preparative HPLC followed by recrystallization from ethyl acetate gave the title compound (lOlmg) as yellow needles. m.p. 209"C MS APCI (+ve) 292(M+H)+).

1H NMR (DMSO-d6) # 2.57 (3H, s), 2.78 (3H, s), 7.53 (1H, d), 7.74 (1H, t), 7.83 (1H, t), 8.39 (2H, m), 9.18 (lH,d).

Example 66 9-Fluoro-4,5-dihydro-3-hydroxy-2-(6-methyl-3-pyridinyl)-[1,2 ,3]triazolo[1,5-a]- quinolinium hydroxide, inner salt.

Prepared by the route of Example 3 using 8-fluoro-1 ,2,3,4-tetrahydroquinoline-2- carboxylic acid (Example 1 lc) (2.2g) and S-amino-2-methylpyridine (1.0g) to give the title compound (0.23g) as a beige solid. m.p. 178-179°C.

MS APCI (+ve) 297 ((M+H)+).

1H NMR (DMSO-d6) 8 2.55 (3H, s), 2.88 (2H, m), 3.10 (2H, t), 7.37-7.56 (4H, m), 8.30 (1H, dd), 9.12 (lH,d).

Example 67 9-Fluoro-3-hydroxy-2-(6-methyl-3-pyridinyl)-[1,2,3]triazolo[ 1,5-a]quinolinium hydroxide, inner salt.

Prepared by the route of Example 20 using 9-fluoro-4,5-dihydro-3-hydroxy-2-(6-methyl-3- pyridinyl)-[l,2,3]triazolo[l,5-a]quinolinium hydroxide, inner salt (Example 66) (0.68g) to give the title compound (0.16g) as a yellow solid. m.p. 205°C MS APCI(+ve) 295 ((M+H)+).

1H NMR (DMSO-d6) # 2.57 (3H, s), 7.50 (2H, m), 7.74 (3H, m), 7.86 (1H, dd), 8.37 (lH, dd), 9.19 (lH, d).

Example 68 9-Fluoro-4,5-dihydro-3-hydroxy-4-methyl-2-(6-methyl-3-pyridi nyl) [1,2,3] triazolo [1,5-a] quinolinium hydroxide, inner salt.

Prepared by the route of Example 3 using 8-fluoro-3-methyl-1,2,3,4-tetrahydroquinoline-2- carboxylic acid hydrochloride (Example 23b)(2.27g) and 5-amino-2-methylpyridine (1.0g) to give the title compound (0.22g) as a beige solid. m.p. 164-166"C.

MS APCI (+ve) 311 ((M+H)+). lH NMR (DMSO-d6) 6 1.29 (3H, d), 2.55 (3H, s), 2.90 (1H, dd), 3.20 (1H, dd), 3.30 (1H, m), 7.37 (1H,d), 7.53 (3H, m), 8.30 (1H, dd), 9.12 (1H, d).

Example 69 9-Fluoro-3-hydroxy-4-methyl-2-(6-methyl-3-pyridinyl)-[1,2,3] triazolo[1,5- a]quinolinium hydroxide, inner salt.

Prepared by the route of Example 20 using 9-fluoro-4,5-dihydro-3-hydroxy-4-methyl-2-(6- methyl-3-pyridinyl)-[ 1 ,2,3]triazolo[ 1 ,5-a]quinolinium hydroxide, inner salt (Example 68) (0.Sg) to give the title compound (0.15g) as a yellow solid. m.p. 234-235°C MS APCI (+ve) 309 ((M+H)+).

1H NMR (CDCl3)# 2.65 (3H, s), 2.76 (3H, s), 6.90 (1H, s), 7.34 (2H, m), 7.44 (1H, d), 7.54 (1H, m), 8.51 (1H, dd), 9.35 (1H, d).

Example 70 4,5-Dihydro-3-hydroxy-2-(3-trifluoromethylphenyl)-[1,2,3]tri azolo[1,5-a]quinolinium hydroxide, inner salt.

Prepared by the route of Example 3 using 1,2,3,4-tetrahydro-quinoline-2-carboxylic acid (6.0g) and 3-trifluoromethylaniline (5.46g) to give the title compound (2.21g) as a yellow solid. m.p. 182-184°C.

MS APCI (+ve) 332 ((M+H)+). lH NMR (CDCl3) 8 3.08 (4H, s), 7.43 (3H, m), 7.64 (2H, m), 8.05 (1H, m), 8.46 (1H, s), 8.57 (1H,m).

Example 71 3-Hydroxy-2-(3-trifluoromethylphenyl)-[1,2,3]triazolo[1,5-a] quinolinium hydroxide, inner salt.

Prepared by the route of Example 9 using 4,5-dihydro-3-hydroxy-2-(3- trifluoromethylphenyl)-[ 1 ,2,3]triazolo[ 1 ,5-a]quinolinium hydroxide, inner salt (Example 70) (4.08g) to give the title compound (1.78g) as a yellow solid. m.p. 168-169°C MS APCI (+ve) 330 ((M+H)+). lH NMR (CDCl3) # 7.21 (1H, d), 7.77 (5H, m), 7.85 (1H, d), 8.55 (2H, m), 8.65 (1H, d).

Example 72 2-(4-Fluorophenyl)-3-hydroxy-4-methyl-[1,2,3]triazolo[1,5-a] quinolinium hydroxide, inner salt.

(a) 4,5-Dihydro-2-(4-fluorophenyl)-3-hydroxy-[1,2,3]triazolo[1,5 -a]quinolinium hydroxide, inner salt.

Prepared by the route of Example 3 using 3-methyl-l,2,3,4-tetrahydroquinoline-2- carboxylic acid hydrochloride (Example 18c) (S.lg) and 4-fluoroaniline (2.12ml) to give the subtitle compound (0.4g) as a yellow solid.

(b) 2-(4-Fluorophenyl)-3-hydroxy-4-methyl-[1,2,3]triazolo[1,5-a] quinolinium hydroxide, inner salt.

Prepared by the route of Example 9 using 4,5-dihydro-2-(4-fluorophenyl)-3-hydroxy- [1,2,3]triazolo[l ,5-a]quinolinium hydroxide, inner salt.(0.4g) to give the title compound (0. 14g) as a yellow solid. m.p. 215-216°C MS APCI (+ve) 294 ((M+H)+).

H NMR (CDC13) 6 2.76 (3H, s), 6.92 (1H, s), 7.20 (2H, m), 7.61 (2H, m), 7.69 (1H, m), 8.25 (2H, m), 8.44 (1H, m).

Example 73 3-Hydroxy-5-nitro-2-(3-trifluoromethylphenyl)-[1,2,3]triazol o[1,5-a]quinolinium hydroxide, inner salt.

Prepared by the route of Example 51 using 3-hydroxy-2-(3-trifluoromethylphenyl)- [1,2,3]triazolo[1,5-a]quinolinium hydroxide, inner salt (Example 71)(0.25g) to give the title compound (0.19g) as an orange solid. m.p. >250°C MS APCI (+ve) 375 ((M+H)+). lH NMR (CDCl3) 8 7.70 (2H, m), 7.89 (2H, m), 8.44 (1H, s), 8.57 (1H, m), 8.68 (1H, m), 8.74 (1H, s), 8.89 (1H, m).

Example 74 5-Bromo-3-hydroxy-2-(3-trifluoromethylphenyl)-[1,2,3]triazol o[1,5-a]quinolinium hydroxide, inner salt Prepared by the route of Example 30 using 3-hydroxy-2-(3-trifluoromethylphenyl)- [1,2,3]triazolo[l ,5-a]quinolinium hydroxide, inner salt (Example 71) (0.85g) to give the title compound (0.39g) as a yellow solid. m.p. 205-206°C MS APCI (+ve) 410 ((M+H)+). lH NMR (CDCl3) 6 7.64 (2H, m), 7.83 (2H, m), 7.97 (1H, s), 8.22 (1H, m), 8.52 (1H, s), 8.59 (2H, m).

Example 75 5-(1-Azetidinyl)-3-hydroxy-2-(3-trifluoromethylphenyl)-[1,2, 3]triazolo[1,5- a]quinolinium hydroxide, inner salt A solution of 5-bromo-3-hydroxy-2-(3-trifluoromethylphenyl)-[1,2,3]triazol o[1,5- a]quinolinium hydroxide, inner salt (Example 74) (0.25g), tris(dibenzylideneacetone)dipalladium (11 mg), (R)-(+)-2,2-bis(diphenylphosphino)- 1,1 - binaphthyl (23mg), azetidine (0. 13ml) and sodium tertiary butoxide (82mg) in toluene (20ml) was heated at 80°C in a sealed tube overnight. Purification by chromatography on silica gel (ethyl acetate) followed by a diethyl ether wash gave the title compound (0.1 9g) as an orange solid. m.p. 221-222"C MS APCI (+ve) 385 ((M+H)+). lH NMR (CDC13) 6 2.47 (2H, m), 4.19 (4H, t), 6.61 (1H, s), 7.64 (3H, m), 7.73 (1H, td), 7.96 (lH, dd), 8.56 (2H, br d), 8.67 (1H, d).

Example 76 2-(3-Fluorophenyl)-4,5-dihydro-3-hydroxy-4-oxo-[1,2,3]triazo lo[1,5-a]quinoxalinium hydroxide, inner salt Prepared as for Example 48 employing 3-fluoroaniline and methyl 2- (carboxymethylamino)benzoate to give the title compound as a colourless solid. m.p. >250°C MS APCI (+ve) 297 ((M+H)+). lH NMR (DMSO-d6) 87.35 (3H, m), 7.65 (2H, m), 8.03 (2H, m), 8.26 (1H, dd), 11.66 (lH, s).

Example 77 2-(3-Fluorophenyl)-3-hydroxy-5-nitro- [1,2,3]triazolo[1 ,5-a]quinolinium hydroxide, inner salt.

Prepared by the route of Example 51 using 2-(3-fluorophenyl)-3-hydroxy- [1,2,3]triazolo[l ,5-a]quinolinium hydroxide, inner salt (Example 103) (2.0g) to give the title compound (0.4g) as an orange solid.

m.p. 221-223°C MS APCI (+ve) 325 ((M+H)+). lH NMR (CDCl3) # 7.16 (1H, m), 7.55 (1H, m), 7.88 (2H, m), 8.01 (1H, m), 8.09 (1H, dd), 8.63 (1H, m), 8.73 (1H, s), 8.88 (1H, m).

Example 78 3-Hydroxy-4-methyl-2-(6-methyl-3-pyridinyl)-[1,2,3]triazolo[ 1,5-a]quinolinium hydroxide, inner salt.

(a) 4,5-Dihydro-3-hydroxy-4-methyl-2-(6-methyl-3-pyridinyl)-[1,2 ,3]triazolo[1,5- a]quinolinium hydroxide, inner salt.

Prepared by the route of Example 3 using 3-methyl- 1,2,3,4-tetrahydroquinoline-2- carboxylic acid hydrochloride (Example 18c) (7.48g) and S-amino-2-methylpyridine (4.2g) to give the subtitle compound (1.21g) as a yellow solid.

(b) 3-Hydroxy-4-methyl-2-(6-methyl-3-pyridinyl)-[1,2,3]triazolo[ 1,5-a]quinolinium hydroxide, inner salt.

Prepared by the route of Example 9 using 4,5-dihydro-3-hydroxy-4-methyl-2-(6-methyl-3- pyridinyl)-[1,2,3]triazolo[1,5-a]quinolinium hydroxide, inner salt (1.54g) to give the title compound (0.96g) as a yellow solid. m.p. 231-232°C MS APCI (+ve) 291 ((M+H)+).

lH NMR (CDCl3) 8 2.65 (3H, s), 2.77 (3H, d), 6.94 (1H, s), 7.32 (lH, d), 7.63 (2H, m), 7.69 (lH, m), 8.46 (lH, m), 8.56 (lH, dd), 9.31 (lH, d).

Example 79 3-Hydroxy-4-methyl-2-(6-methyl-3-pyridinyl)-5-nitro-[1,2,3]t riazolo[1,5- a]quinolinium hydroxide, inner salt.

Prepared by the route of Example S 1 using 3-hydroxy-4-methyl-2-(6-methyl-3-pyridinyl)- [1,2,3]triazolo[l ,5-a]quinolinium hydroxide, inner salt (Example 78) (0.3g) to give the title compound (0.4g) as an orange solid. m.p. 202-204°C MS APCI (+ve) 336 ((M+H)+). lH NMR (CDCl3) 8 2.66 (3H, s), 2.84 (3H, s), 7.35 (1H, d), 7.80 (3H, m), 8.47 (1H, dd), 8.55 (1H, m), 9.25 (1H, d).

Example 80 3-Hydroxy-2-(6-methyl-3-pyridinyl)-5-nitro-[1,2,3]triazolo[1 ,5-a]quinolinium hydroxide, inner salt.

Prepared by the route of Example 51 using 3-hydroxy-2-(6-methyl-3-pyridinyl)- [1,2,3]triazolo[1,5-a]quinolinium hydroxide, inner salt.(1.8g) to give the title compound (0. 14g) as a red solid. m.p. 249-251°C MS APCI (+ve) 322 ((M+H)+). lH NMR (CDC13) # 2.68 (3H, s), 7.37 (1H, d), 7.88 (2H, m), 8.50 (1H, m), 8.64 (1H, m), 8.73 (1H, s), 8.89 (1H, m), 9.24 (1H, d).

Example 81 2-(3-Fluorophenyl)-4,5-dihydro-3-hydroxy-5-methyl-4-oxo-[1,2 ,3]triazolo[1,5-a]- quinoxalinium hydroxide, inner salt.

To a stirred solution of 2-(3-fluorophenyl)-4,5-dihydro-3-hydroxy-4-oxo- [1,2,3]triazolo[l ,5-a]quinoxalinium hydroxide, inner salt (Example 76) (0.30g) in dimethylformamide (10ml) was added methyl iodide (0.13ml) followed by sodium hydride

(0. 16g, 60% dispersion in mineral oil). After 16h the reaction was carefully quenched with water (1 00ml) and the aqueous phase was extracted with dichloromethane/methanol (3x30ml). The combined organic phase was washed with brine, dried over sodium sulfate, filtered then concentrated in vacua. Recrystallization from methanol/ethyl acetate gave the title compound (0.14g). m.p. >250°C MS APCI (+ve) 311 ((M+H)+). lH NMR (DMSO-d6) 8 3.55 (3H, s), 7.36 (lH, m), 7.46 (lH, m), 7.68 (2H, m), 7.76 (lH, m), 8.05 (2H, m), 8.36 (lH, dd).

Example 82 2-(3-Fluorophenyl)-3-hydroxy-4-(1 -methylethyl)-[1,2,3]triazolo[1,5-a]quinoxalinium hydroxide, inner salt.

Chlorotrimethylsilane (0.56ml) was added to a stirred suspension of 2-(3-fluorophenyl)- 4,5-dihydro-3-hydroxy-4-oxo-[ 1 ,2,3]triazolo [1 ,5-a]quinoxalinium hydroxide, inner salt (Example 76) (l.Og) and triethylamine (0.61ml) in toluene (30ml) and the mixture was warmed to 400C for 4h. The reaction mixture was then cooled in an ice bath and a solution of isopropylmagnesium chloride (2M in diethyl ether, 5. lml) was added dropwise then this mixture was allowed to warm to room temperature slowly over 16h. The mixture was warmed to 400C for lh before being cooled and diluted with saturated aqueous ammonium chloride (SOml) and extracted with dichloromethane (3x30ml). The combined organic phase was washed with brine, dried over sodium sulfate, filtered then concentrated in

vacuo. Purification by chromatography on silica gel (dichloromethane) followed by a diethyl ether wash gave the title compound (0.1 lg) as a beige solid. m.p. 152-l530C MS APCI (+ve) 323 ((M+H)+).

1H NMR (CDCl3) 8 1.46 (6H, d), 4.06 (1H, m), 7.14 (lH, m), 7.52 (lH, m), 7.63 (lH, td), 7.75 (1H, td), 8.07 (3H, m), 8.38 (1H, dd).

Example 83 2-(3-Fluorophenyl)-3-hydroxy-4-methyl-[1,2,3]triazolo[1,5-a] quinoxalinium hydroxide, inner salt.

Chlorotrimethylsilane (0.37ml) was added to a stirred suspension of 2-(3-fluorophenyl)- 4,5-dihydro-3 -hydroxy4-oxo-[l ,2,3]triazolo[l ,5-a]quinoxalinium hydroxide, inner salt (Example 76) (0.66g) and triethylamine (0.4ml) in toluene (20ml) and the mixture was warmed to 400C for 4h. The reaction mixture was then cooled in an ice bath and a solution of methylmagnesium chloride (3M in tetrahydrofuran, 2.2ml) was added dropwise before warming to 400C for 3h. The mixture was then stirred at room temperature for 16h then diluted with saturated aqueous ammonium chloride (50ml) and extracted with dichloromethane (3x30ml). The combined organic phase was washed with brine, dried over sodium sulfate, filtered then concentrated in vacuo. Purification by chromatography on silica gel (methanol/dichloromethane, 3/97) followed by a diethyl ether wash gave the title compound (17mg) as a beige solid. m.p. 171-174"C MS APCI (+ve) 295 ((M+H)+).

lH NMR (CDCl3) 6 2.97 (3H, s), 7.10 (1H, td), 7.53 (1H, m), 7.65 (1H, td), 7.76 (1H, td), 8.05 (3H, m), 8.39 (1H, dd).

Example 84 3-Hydroxy-4-methyl-2-(4-methylphenyl)-[1,2,3]triazolo[1,5-a] quinoxalinium hydroxide, inner salt.

(a) 1-(2-Acetylamino)phenyl-4-hydroxy-3-(4-methylphenyl)-[1,2,3] triazolium hydroxide, inner salt.

Prepared as for Example 63a employing 4-toluidine (lOg) and [2-(acetylamino)- phenyl]amino acetic acid, lithium salt (Example 63a, 20g) to give the subtitle compound (5.31g) as a beige solid. m.p. 178-179°C MS APCI (+ve) 309 ((M+H)+).

1H NMR (DMSO-d6) # 2.17 (3H, s), 2.40 (3H, s), 6.95 (1H, s), 7.26 (3H, m), 7.44 (1H, dd), 7.56 (1H, td), 7.88 (2H, d), 8.37 (1H, br d), 8.81 (1H, br s).

(b) 3-Hydroxy-4-methyl-2-(4-methylphenyl)-[1,2,3]triazolo[1,5-a] quinoxalinium hydroxide, inner salt.

Prepared as for Example 63b employing 1 -(2-acetylamino)phenyl-4-hydroxy-3-(4- methylphenyl)-[1,2,3]triazolium hydroxide, inner salt (4.81g) to give the title compound (0.445g) as a yellow solid.

m.p. 192-193°C MS APCI (+ve) 291 ((M+H)+).

1H NMR (DMSO-d6) # 2.38 (3H, s), 2.75 (3H, s), 7.38 (2H, d), 7.70 (1H, td), 7.90 (1H, td), 7.92 (1H, dd), 7.98 (2H, d), 8.34 (1H, dd).

Example 85 3-Hydroxy-2-(6-methoxy-3-pyridinyl)-4-methyl-[1,2,3]triazolo [1,5-a]quinoxalinium hydroxide, inner salt.

(a) 1-(2-Acetylamino)phenyl-4-hydroxy-3-(6-methoxy-3-pyridinyl)- [1,2,3]triazolium hydroxide, inner salt.

Prepared as for Example 63a employing 5-amino-2-methoxypyridine (11.6g) and [2- (acetylamino)phenyl]amino acetic acid, lithium salt (Example 63a, 20g) to give the subtitle compound (7.29g) as an orange solid. m.p. 223-225°C MS APCI (+ve) 326 ((M+H)+).

1H NMR (DMSO-d6) # 2.02 (3H, s), 3.92 (3H, s), 7.03 (1H, dd), 7.39 (1H, t), 7.43 (1H, s), 7.61 (1H, t), 7.68 (1H, dd), 7.89 (1H, d), 8.25 (1H, dd), 8.80 (1H, d), 9.75 (1H, s).

(b) 3-Hydroxy-2-(6-methoxy-3-pyridinyl)-4-methyl-[1,2,3]triazolo [1,5 a]quinoxalinium hydroxide, inner salt.

Prepared as for Example 63b employing 1 -(2-acetylamino)phenyl-4-hydroxy-3-(6- methoxy-3-pyridinyl)-[l ,2,3]triazolium hydroxide, inner salt (6.67g) to give the title compound as a yellow solid. m.p. >250°C MS APCI (+ve) 308 ((M+H)+). lH NMR (CDCl3) 82.94 (3H, s), 3.67 (3H, s), 6.75 (1H, d), 7.65 (1H, td), 7.76 (1H, td), 8.00 (2H, m), 8.31 (1H, dd), 8.73 (1H, d).

Example 86 3-Hydroxy-2-(4-trilIuoromethylphenyl)-[1,2,3]tnazolo[5,1c] [1,2,4]benzotriazinium hydroxide, inner salt (a) 1-(2-Aminophenyl)-4-hydroxy-3-(4-trifluoromethylphenyl)-3H-[ 1,2,3]triazolium hydroxide, inner salt.

To 1 -(2-carboxyphenyl)-4-hydroxy-3- [4-(trifluoromethyl)phenyl]- [1,2,3]triazolium hydroxide, inner salt (Example 48c) (lg) in t-butanol (SOml) was added triethylamine (0.94ml) then diphenylphosphoryl azide (1.29g). The mixture was heated to 80°C for 18h.

The reaction mixture was concentrated in vacuo and suspended in dichloromethane(lOml) before trifluoroacetic acid (10ml) was added. After 30 min the mixture was concentrated in vacuo and partitioned between ethyl acetate and aqueous sodium hydrogen carbonate solution. The organics were collected and dried over magnesium sulfate then concentrated

in vacuo. The resulting yellow solid was recrystallised from ethyl acetate to give the subtitle compound (0.461g).

MS APCI (+ve) 321 ((M+H)+) 1H NMR (CDCl3) 8 4.46 (2H, br s), 6.87-6.93 (2H, m), 7.03 (1H, s), 7.32-7.36 (2H, m), 7.74-7.77 (2H, d), 8.30-8.33 (2H, d).

(b) 3-Hydroxy-2-(4-trifluoromethylphenyl)-[1,2,3]triazolo[5,1-c] [1,2,4]- benzotriazinium hydroxide, inner salt To 1-(2-aminophenyl)-4-hydroxy-3-(4-trifluoromethylphenyl)-3H-[ 1,2,3]triazolium hydroxide, inner salt (0. lg) in water (3.2ml), tetrahydrofuran (I ml) and concentrated hydrochloric acid (0.52ml) at -50C was added a solution of NaNO2 (21mg) in water (0.8ml) dropwise. After 10 min the mixture was allowed to warm to room temperature and the resultant solid was collect by filtration. The solid was then stirred in boiling ethanol (20ml) for S min before being collected by filtration to give the title compound as a yellow powder (24mg). m.p. 317-318°C MS APCI (+ve) 332((M+H)+). lH NMR (DMSO-d6) 6 8.06 (2H, d), 8.09 (1H, dd), 8.12 (1H, dd), 8.46 (2H, d). 8,51 (1H, m), 8.58 (1H, m).

13C NMR (DMSO-d6) 6 114.7,120.7,126.9, 126.8,129.7,132.2, 134.4.

Example 87 2-(6-Chloro-3-pyridinyl)-3-hydroxy-4-methyl-[1,2,3]triazolo[ 1,5-a]quinolinium hydroxide, inner salt (a) 4,5-Dihydro-2-(6-chloro-3-pyridinyl)-3-hydroxy-4-methyl-[1,2 ,3]triazolo[1,5 a]quinolinium hydroxide, inner salt To a solution of 3-amino-6-chloropyridine (4.03g) in water (SOml) and concentrated hydrochloric acid (1 lml) at 0°C was added a solution of NaNO2 (2.28g) in water (25ml) dropwise maintaining a temperature of 0°C. lSmin after complete addition the mixture was added to a solution of 3-methyl- ,2,3,4-tetrahydroquinoline-2-carboxylic acid (Example 18c) (6g) in pyridine (54ml) at 0°C maintaining the temperature below 5"C. After lh the mixture was partitioned between ethyl acetate and water. The organic layer was collected and dried over magnesium sulfate. The solution was partially concentrated in vacuo and then treated with acetic anhydride (lOml). After 1 hour the mixture was partitioned between ethyl acetate and aqueous sodium hydrogen carbonate solution, filtered and the organics were dried over magnesium sulfate. After concentration in vacuo the product was stirred in diethyl ether to give the subtitle compound as a tan solid (3.2g).

(b) 2-(6-Chloro-3-pyridinyl)-3-hydroxy-4-methyl-[1,2,3]triazolo[ 1,5-a]quinolinium hydroxide, inner salt A suspension of 4,5-dihydro-2-(6-chloro-3-pyridinyl)-3-hydroxy-4-methyl- [1,2,3]triazolo[1,5-a]quinolinium hydroxide, inner salt (3g) and MnO2 (Sg) in chloroform was heated at reflux for 16 hours before a further amount of MnO2 (Sg) was added and the

suspension stirred at reflux for 48h. The mixture was filtered and washed with dichloromethane. The organics were concentrated in vacuo and chromatographed on silica eluting with ethyl acetate. The product was washed with diethyl ether and rechromatographed on silica (ethyl acetate) to give the title compound (0.2g). m.p. 250-251°C MS APCI (+ve) 311 ((M+H)+). lH NMR (CDCL3) 8 2.78 (3H, s), 7.00 (1H, s), 7.49 (1H, d), 7.66 (2H, m). 7.73 (1H, m), 8.48 (1H, m), 8.76 (lH,dd), 9.31 (lH,d).

Example 88 4-Azetidinyl-3-hydroxy-2-(4-chlorophenyl)-[1,2,3]triazolo[1, 5a]quinoxalinium hydroxide, inner salt A stirred suspension of 2-(4-chlorophenyl)-3-hydroxy-4-oxo-4,5-dihydro- [1 ,2,3]triazolo [1 ,5-a]quinoxalinium hydroxide, inner salt (example 55) (0.550g) in phosphorous oxychloride (lOml) was heated at reflux under a nitrogen atmosphere for Sh.

The mixture was concentrated in vacuo azeotroping with toluene and the residue then partitioned between dichloromethane and aqueous sodium hydrogen carbonate solution.

The organics were dried over magnesium sulfate and concentrated in vacuo. The residue was then stirred in 15 ml of dichloromethane and to this solution was added excess azetidine. After lh the solution was concentrated in vacuo and chromatographed on silica eluting with ethyl acetate. The product was recrystallised from ethyl acetate to give the title compound (3mg).

MS APCI (+ve) 352/354((M+H)+).

1H NMR (DMSO-d6) 6 2.45 (2H, m), 4.55 (4H, m), 7.35 (1H, t), 7.51 (2H, d). 7.57 (1H, t), 7.63 (1H, d), 8.12(2H, d), 8.18 (1H,d).

Example 89 2-(6-Chloro-3-pyridinyl)-3-hydroxy-4-methyl-5-nitro-[1,2,3]t riazolo[1,5-a]- quinolinium hydroxide, inner salt Prepared by the route of Example 51 using 2-(6-chloro-3-pyridinyl)-3-hydroxy-4-methyl- [1 ,2,3]triazolo[ 1 ,5-a]quinolinium hydroxide, inner salt (Example 87) (1g) to give, after recrystallization from ethyl acetate, the title compound (0.39g). m.p. 230-232°C MS APCI (+ve) 356((M+H)+).

1H NMR (CDCl3) # 2.85 (3H, s), 7.53 (1H, d), 7.79 (3H, m), 8.55 (1H, m). 8.68 (1H, dd), 9.25 (1H, d).

Example 90 2-(4-Chlorophenyl)- 3-hydroxy-4-methyl-[1,2,3]triazolo[1,5-a]quinolinium hydroxide, inner salt.

(a) 2-(4-Chlorophenyl)-4,5-dihydro-3-hydroxy-4-methyl-[1,2,3]tri azolo[1,5-a]- quinolinium hydroxide, inner salt.

To a stirred solution of 4-chloroaniline (2.66g) in a mixture of water (SOml) and concentrated hydrochloric acid (l0ml) at O to -50C was added portionwise a solution of sodium nitrite (l.Slg) in water (17ml). The solution was stirred 30 minutes at O to -50C and then was added portionwise to a solution of 3-methyl-l,2,3,4-tetrahydroquinoline-2- carboxylic acid (Example 18c) (Sg) in pyridine (20ml) at O to -5°C. The solution was stirred for 0.5 hour at O to -5°C, extracted into ethyl acetate (twice), dried over magnesium sulphate and concentrated in vacuo. To the residue was added pyridine (50ml) then acetic anhydride (8ml) and the solution was stirred for 2 hours. The pyridine was removed in vacuo and the residue partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The aqueous layer was extracted once more with ethyl acetate and the combined ethyl acetates were dried over magnesium sulfate and concentrated in vacuo.

Purification by chromatography on silica gel (ethyl acetate) gave the title compound (1.18g).

MS APCI (+ve) 312 ((M+H)+).

(b) 2-(4-Chlorophenyl)-3-hydroxy-4-methyl-[1,2,3]triazolo[1,5-a] quinolinium hydroxide, inner salt.

2-(4-Chlorophenyl)-4,5-dihydro-3-hydroxy-4-methyl-[1,2,3] triazolo[1,5-a]quinolinium hydroxide, inner salt (1.18g) was dissolved in chloroform (50 ml) and manganese dioxide (3.3 g) was added. The mixture was refluxed for 22 hours, filtered through Celite and concentrated in vacuo. Purification by chromatography on silica gel (1:1 ethyl acetate: iso- hexane) followed by trituration with diethyl ether gave the title compound (0.49 g). m.p. 229°C MS APCI (+ve) 310 ((M+H)+) lH NMR (CDC13) 6 2.77 (3H, s), 6.92 (1H, s), 7.45-7.54 (2H, m), 7.59-7.67 (2H, m), 7.68-7.72 (1H, m), 8.24-8.30 (2H, m), 8.42-8.48 (1H, m).

3C NMR (CDC13) 816.65, 115.62, 118.88, 122.05, 127.78, 128.15, 129.04, 129.19, 130.36, 132.91, 135.10, 153.96.

Example 91 2-(4-Chlorophenyl)-3-hydroxy-4-methyl-5-nitro-[1,2,3]triazol o[1,5-a]quinolinium hydroxide, inner salt.

2-(4-Chlorophenyl)-3-hydroxy-4-methyl-[1,2,3]triazolo[1,5 -a]quinolinium hydroxide, inner salt (Example 90) (0.20 g) was dissolved in dichloromethane (15 ml) and nitronium tetrafluoroborate (0.SM solution in sulfolane) was added dropwise until there was no starting material left by thin layer chromatography (ca. 2 ml). The mixture was partitioned between dichloromethane and saturated aqueous sodium bicarbonate solution. The aqueous

layer was extracted twice more with dichloromethane and the combined dichloromethanes were dried over magnesium sulfate and concentrated in vacuo. The resultant slurry was triturated with diethyl ether to give the title compound as an orange solid (0.14 g). m.p. 221"C MS APCI (+ve) 355 ((M+H)+) lH NMR (CDCl3) 82.84 (3H, s), 7.48-7.55 (2H, m), 7.74-7.82 (3H, m), 8.17-8.22 (2H, m), 8.50-8.58 (1H, m).

13C NMR (CDCl3) # 11.86, 115.06, 116.03, 120.29, 122.30, 123.62, 126.19, 128.91, 129.52, 130.05, 130.51, 133.91, 134.39, 154.73.

Example 92 5-Amino-2-(4-chlorophenyl)-3-hydroxy-4-methyl-[1,2,3]triazol o[1,5-a]quinolinium hydroxide, inner salt.

2-(4-Chlorophenyl)-3-hydroxy-4-methyl-5-nitro-[ 1 ,2,3]triazolo [1 ,5-a]quinolinium hydroxide, inner salt (Example 91) (0.80 g) and 10% palladium on charcoal (0.1 g) in ethanol (150 ml) and tetrahydrofuran (300 ml) were hydrogenated at 1 atm for 30 minutes, filtered through Celite and concentrated in vacuo. Purification by chromatography on silica gel (ethyl acetate) gave the title compound (0. 14g). m.p. 247°C MS APCI (+ve) 325 ((M+H)+)

1H NMR (DMSO-d6) 8 2.53 (3H,br s), 5.90 (2H, br s), 7.61-7.67 (2H, m), 7.73-7.79 (2H, m), 8.30-8.35 (3H, m), 8.48-8.51 (1H, m).

Example 93 5-Amino-9-fluoro-3-hydroxy-2-(6-methyl-3-pyridinyl)-[1,2,3]t riazolo[1,5-a]- quinolinium hydroxide, inner salt.

9-Fluoro-3-hydroxy-2-(6-methyl-3-pyridinyl)-5-nitro-[1,2, 3]triazolo[1,5-a]quinolinium hydroxide, inner salt (0.03g) and 10% palladium on charcoal (0.05 g) in ethanol (50 ml) and tetrahydrofuran (50 ml) were hydrogenated at 1 atm for 30 minutes, filtered through Celite and concentrated in vacuo. Purification by chromatography on silica gel (9:1:0.05 dichloromethane: methanol: ammonia) gave the title compound (0.015 g).

MS APCI (+ve) 310 ((M+H)+) lH NMR (DMSO-d6) 8 2.55 (3H, s), 6.36 (2H, s), 6.71 (1H, s), 7.47-7.50 (1H, d), 7.72-7.81 (2H, m), 8.05-8.07 (1H, d), 8.40-8.43 (1H, dd), 9.25 (1H, d).

Example 94 2-(4-Chlorophenyl)-3-hydroxy-5-methyl-[1,2,3]triazolo[1,5-a] quinolinium hydroxide, inner salt 5-Bromo-2-(4-chlorophenyl)-3-hydroxy-[1,2,3]triazolo[1,5-a]q uinolinium hydroxide, inner salt (Example 47) (0.338 g), tetramethyl tin (5 ml), trans-benzyl(chloro)- bis(triphenylphosphine)palladium (II) (0.020 g) and dimethylformamide (30 ml) were heated together at 600C under nitrogen for 16 hours, cooled, diluted with ethyl acetate, washed well with water, dried over magnesium sulfate and concentrated in vacuo.

Purification by chromatography on silica gel (6:1 dichloromethane: ethyl acetate) gave the title compound (0.121 g). m.p. 213°C MS APCI (+ve) 310 ((M+H)+) lH NMR (CDC13) 82.60 (3H, m), 7.48-7.51 (3H, m), 7.69-7.76 (2H, m), 7.91-7.96 (1H, m), 8.26-8.29(2H, d), 8.53-8.58 (1H, m).

13C NMR (CDCl3) # 18.82, 116.02, 116.20, 118.70, 122.20, 125.67, 127.51, 128.15, 129.09, 129.19, 129.28, 130.15, 132.97, 135.22.

Example 95 2-(4-Chlorophenyl)-3-hydroxy.5-nitro-[1,2,3]triazolo[1 ,5-a] quinolinium hydroxide, inner salt.

2-(4-Chlorophenyl)-3-hydroxy-[ 1 ,2,3]triazolo[ I ,S-a]quinolinium hydroxide, inner salt (Example 46) (1.00g) was dissolved in dichloromethane (75 ml) and nitronium tetrafluoroborate (0.SM solution in sulfolane) was added dropwise until there was no starting material left by thin layer chromatography (ca. 12 ml). The mixture was partitioned between dichloromethane and saturated aqueous sodium bicarbonate solution. The aqueous layer was extracted twice more with dichloromethane and the combined dichloromethanes were dried over magnesium sulfate and concentrated in vacuo. Purification by chromatography on silica gel (19:1 dichloromethane: ethyl acetate) followed by recrystallisation from dichloromethane gave the title compound (0.279 g). m.p. 285"C MS APCI (+ve) 340 ((M+H)+) lH NMR (CDCl3/DMSO-d6) 8 7.55-7.61 (2H, m), 7.89-7.96 (2H, m), 8.20-8.26 (2H, m), 8.64-8.68 (2H, m), 8.82-8.85 (1H, m).

Example 96 5-Amino-2-(4-chlorophenyl)-3-hydroxy-[1,2,3]triazolo[1,5-a]q uinolinium hydroxide, inner salt.

2-(4-Chlorophenyl)-3-hydroxy-5-nitro- [1 ,2,3]triazolo[ 1 ,5-a]quinolinium hydroxide, inner salt (Example 95) (0.376g) and 10% palladium on charcoal (0.07g) in ethanol (75 ml) and tetrahydrofuran (150 ml) were hydrogenated at 1 atm for 30 minutes, filtered through Celite and concentrated in vacuo. Purification by chromatography on silica gel (9:1 ethyl acetate: ethanol) gave the title compound (0.063g). m.p. >300°C MS APCI (+ve) 311 ((M+H)+) H NMR (DMSO-d6/ CDC13) 8 6.81 (1H, s), 7.48-7.53 (2H, m), 7.71-7.83 (2H, m), 8.19-8.22 (1H, dd), 8.28-8.33 (2H, m), 8.52-8.56 (1H, dd).

Example 97 5-(2-Aminoethyl)amino-2-(4-chlorophenyl)-3-hydroxy-[1,2,3]tr iazolo[1,5- a]quinolinium hydroxide, inner salt, dihydrochloride 5-Bromo-2-(4-chlorophenyl)-3-hydroxy-[1,2,3]triazolo[1,5-a]q uinolinium hydroxide, inner salt (Example 47) (0.633 g), tert-butyl-N-(2-aminoethyl)carbamate (0.76 g), sodium tert- butoxide (0.228 g), tris(dibenzylideneacetone)dipalladium (0) (0.032 g), (R)-(+)-2,2- bis(diphenylphosphino)- 1,1 -binaphthyl (0.064 g) and toluene (70 ml) were refluxed together under nitrogen for 23 hours. The mixture was cooled and 2-(4-chlorophenyl)-5-[2- (1,1-dimethylethyloxycarbonylamino)ethylamino]-3-hydroxy-[1, 2,3]triazolo[1,5- a]quinolinium hydroxide, inner salt was obtained by chromatography on silica gel (29:1 ethyl acetate: ethanol). Dichloromethane (5 ml) and trifluoroacetic acid (5 ml) were added and the mixture stirred at room temperature for 1 hour, then concentrated in vacuo. The residue was treated with 1M hydrochloric acid in diethyl ether (4 x 10 ml), concentrated in vacuo and the resultant solid triturated with methanol to give the title compound (0.095 g). m.p. 267°C MS APCI (+ve) 354 ((M+H)+) lH NMR (CDCl3/DMSO-d6) 8 3.15-3.20 (2H, m), 3.48-3.64 (2H, br m), 6.57 (1H, br s), 6.86 (1H, br s), 7.60-7.63 (2H, d), 7.78-7.89 (2H, m), 7.90-8.08 (2H, br s), 8.32-8.35 (2H, d), 8.38-8.41 (1H, d), 8.53-8.56 (1H, d).

Example 98 4,5-Dihydro-3-hydroxy-5-oxo-4-propyl-2-[4-(trifluoromethyl)p henyl] - [1,2,3]triazolo[1 ,5-a]quinazolinium hydroxide, inner salt.

To a solution of 4,5-dihydro-3-hydroxy-5-oxo-2-[4-(trifluoromethyl)phenyl]- [1,2,3]triazolo[1,5-a]quinazolinium hydroxide, inner salt (Example 6) (0.35g) and sodium hydride (0.05g - 60% dispersion in mineral oil) in dimethylformamide (20ml) was added propyl bromide (0.12ml) and the reaction mixture was stirred at room temperature for 2 days. The solution was quenched with water, filtered and dried in vacuo. This was purified by column chromatography(silica-2: 1 ether/isohexane). Recrystallisation from cyclohexane gave the title compound (0.09g) as a yellow solid. m.p. 201-203°C MS APCI (+ve) 389 ((M+H)+) H NMR (DMSO-d6) 80.93 (3H,t), 1.81 (2H,sex), 4.40 (2H, t), 7.85 (1H, t), 8.04 (2H, d), 8.07 (1H, d,t), 8.34 (2H, m), 8.49 (2H, d).

Example 99 4-(2-Aminoethyl)-4,5-dihydro-3-hydroxy-5-oxo-2-[4-(trifluoro methyl)phenyl] - [1,2,3]triazolo[1,5-a]quinazolinium hydroxide, inner salt.

(a) 4- [2-(N-Benzene-1,2-dicarboximido)ethyl-4,5-dihydro-3-hydroxy- 5-oxo-2-[4 (trifluoromethyl)phenyl] - [1,2,3]triazolo[1 ,5-a] quinazolinium hydroxide, inner salt.

To a solution of 4,5-dihydro-3-hydroxy-5-oxo-2- [4-(trifluoromethyl)phenyl]- [1,2,3]triazolo[1,5-a]quinazolinium hydroxide, inner salt (6.8g) (Example 6) and sodium hydride (0. 14g - 60% dispersion in mineral oil) in dimethylformamide (300ml) was added 2-(phthalimino)ethyl trifluoromethanesulfonate (14.0g) (ref:Anal. Sci (1990), 6(1), 49-52.) and the reaction mixture stirred at room temperature for 24 hours. The solution was quenched with water, filtered and dried in vacuo. This was purified by column chromatography(silica - 7:1 dichloromethane/ethyl acetate) to give a yellow solid (7.4g). m.p. >230°C MS APCI (+ve) 520 ((M+H)+) lH NMR (DMSO-d6) 84.06 (2H, m), 4.72 (2H, m), 7.69 (4H, m), 7.86 (3H,m), 8.00 (2H, d), 8.10 (1H, t), 8.29 (1H, d),8.35(1H,d).

(b) 4-(2-Aminoethyl)-4,5-dihydro-3-hydroxy-5-oxo-2-[4-(trifluoro methyl)phenyl]- [1 ,2,3]triazolo[1,5-a] quinazolinium hydroxide, inner salt.

4- [2-(N-B enzene- 1 ,2-dicarboximido)ethyl-4,5-dihydro-3-hydroxy-S-oxo-2- [4- (trifluoromethyl)phenyl]-[1,2,3]triazolo[1,5-a]quinazolinium hydroxide, inner salt. (6.9g) was suspended in ethanol (1200ml) and hydrazine hydrate (2.4ml) and heated to reflux for 2 days. The solvents were removed in vacuo and the residue purified by column chromatography(silica -12:1 dichloromethane/methanol) followed by recrystallisation from ethanol to give a yellow powder (0.055g). m.p. 203-205°C MS APCI (+ve) 390 ((M+H)+) lH NMR (DMSO-d6) 8 1.71 (2H, s), 2.92 (2H, t), 4.46 (2H, t), 7.88 (lH,t), 8.04 (2H, d), 8.07 (1H, t), 8.31 (1H, d), 8.34(1H,d), 8.49 (2H,d).

Example 100 3-Hydroxy-5-(2-methoxyethylamino)-2-[4-(trifluoromethyl)phen yl] - [1,2,3] triazolo[1 ,5-a] quinolinium hydroxide, inner salt.

A solution of S-bromo-3-hydroxy-2-[4-(trifluoromethyl)phenyl]- [1 ,2,3]triazolo [1 ,5- a]quinolinium hydroxide, inner salt (Example 30) (1.0g), tris(dibenzylideneacetone)dipalladium (0.045g), (R)-(+)-2,2-bis(diphenylphosphino)- 1,1- binaphthyl (0.092g), 2-methoxyethylamine (0.SSg) and sodium tertiary butoxide (0.33g) in toluene (20ml) was heated at 80°C overnight. Purification by chromatography on silica gel (dichloromethane: ethyl acetate/ 1:1 to 1:3) followed by a diethyl ether wash gave the title compound (0.59g) as a yellow solid. m.p. >250°C

MS APCI (+ve) 403 ((M+H)+). lH NMR (DMSO) # 3.48 (2H, m), 3.66 (2H, t), 6.45 (1H, s), 6.80 (1H, t), 7.83 (1H, t), 7.90 (1H, t), 7.97 (2H, d), 8.41 (lH,d), 8.56 (3H,d). Example 101 3-Hydroxy-5-methoxy-2-[4-(trifluoromethyl)phenyl]-[1,2,3]tri azolo[1,5-a]quinolinium hydroxide, inner salt.

A solution of 5-bromo-3-hydroxy-2-[4-(trifluoromethyl)phenyl]- [1,2,3]triazolo[1,5- a]quinolinium hydroxide, inner salt (Example 30) (1.5g), tris(dibenzylideneacetone)dipalladium (67.5mg), (R)-(+)-2,2-bis(diphenylphosphino)- 1,1 - binaphthyl (0.138g), 7M ammonia in methanol (lOml) and sodium tertiary butoxide (0.Sg) in toluene (30ml) was heated at 800C in a sealed bomb overnight. Purification by chromatography on silica gel (dichloromethane : ethyl acetate/ 3:1) followed by recrystallisation from ethyl acetate to give the title compound (0.25g) as a yellow solid. m.p. 212-213°C MS APCI (+ve) 360 ((M+H)+). lH NMR (CDCl3) # 4.06 (3H, s), 6.95 (1H, s), 7.72 (1H, m), 7.79 (3H, m), 8.24 (1H, d), 8.53 (3H, m).

Example 102 5-Azetidinylsulfonyl-2-(3-fluorophenyl)-3-hydroxy-[1,2,3]tri azolo[1,5-a]quinolinium hydroxide, inner salt.

A solution of 2-(3-fluorophenyl)-3-hydroxy-[l ,2,3]triazolo[l ,5-a]quinolinium hydroxide, inner salt (Example 103) (1.0g) in an excess of chlorosulfonic acid was stirred over the weekend before being dripped in ice, the solid collected by filtration then dissolved in tetrahydrofuran followed by addition of azetidine (5ml) and stirred at room temperature for 30 minutes. The mixture was concentrated in vacuo and the residue purified by chromatography on silica gel (ethyl acetate) followed by recrystallisation from ethyl acetate to give the title compound (0.20g) as a yellow solid. m.p. >250°C MS APCI (+ve) 399 ((M+H)+). lH NMR (CDC13) 6 2.16 (2H, quin), 3.93 (4H, t), 7.14 (1H, m), 7.30 (1H, d), 7.54 (1H, m), 7.82 (1H, d), 8.01 (1H, d), 8.08 (lH,m), 8.14 (2H,m), 8.98 (lH,s).

Example 103 2-(3-Fluorophenyl)-3-hydroxy-[1,2,3]triazolo[1,5-a]quinolini um hydroxide, inner salt.

(a) 4,5-Dihydro-2-(3-fluorophenyl)-3-hydroxy- [1,2,3]triazolo[1,5-a] quinolinium hydroxide, inner salt.

Prepared by the route of Example 3 using 1,2,3,4-tetrahydro-quinoline-2-carboxylic acid (lSg) and 3-fluoroaniline (9.4g) to give the subtitled compound (14.3g).

MS APCI (+ve) 282 ((M+H)+).

(b) 2-(3-Fluorophenyl)- 3-hydroxy-[1,2,3]triazolo[1,5-a]quinolinium hydroxide, inner salt.

Prepared by the route of Example 9 using 4,5-dihydro-2-(3-fluorophenyl)-3-hydroxy- [1,2,3]triazolo[1,5-a]quinolinium hydroxide, inner salt (14g) to give the title compound (9.7g) as a yellow solid.

MS APCI (+ve) 280 ((M+H)+).

IR 1675, 1492, 1454 lH NMR ( 300 MHz DMSO) 8 7.26-7.34 ( 1H, t ), 7.52 ( 1H d ), 7.63-7.70 (2H, m ), 7.78-7.83 (2H, m), 8.09( lH, d), 8.12-18 (2H, m), 8.57 ( lH, d).

Example 104 2-(4-Fluorophenyl)-3-hydroxy-4-methyl- [1,2,3]triazolo[1,5-a]quinoxalinium hydroxide, inner salt (a) 1-(2-Acetylamino)phenyl-3-(4-fluorophenyl)-4-hydroxy-[1,2,3] triazolium hydroxide, inner salt.

To a solution of 4-fluoroaniline (9.47ml) in water (120ml), tetrahydrofuran (60ml) and concentrated hydrochloric acid (30ml) at -5°C was added a solution of NaNq (7.25g) in water (60ml) dropwise maintaining a temperature of less than 0°C. Once addition was complete the solution was stirred for a further 30min at 0°C then added portionwise to a solution of 2-(acetylamino)phenylamino acetic acid, lithium salt (21.4g) in pyridine (200ml) at -5°C maintaining a temperature of less than 0°C. The mixture was stirred below 0°C for 2h before being partitioned between ethyl acetate and water. The layers were separated and the aqueous extracted with ethyl acetate. The combined organics were dried over magnesium sulfate then concentrated in vacuo until only pyridine remained (ca 30ml volume). To the pyridine solution was added acetic anhydride (SOml) and the solution was allowed to stir for lh. The reaction mixture was concentrated in vacuo and azeotroped with toluene. The resulting semi-solid was triturated with ether and collected then washed with diethyl ether and dried in vacuo to afford the subtitle compound (6.9g).

MS APCI (+ve) 313((M+H)+). lH NMR (CDCl3) 6 2.19 (3H, s), 6.96 (1H, s), 7.13 (2H, m). 7.30 (1H, m), 7.45 (1H, m), 7.58 (1H, m), 8.00 (2H, m), 8.34 (1H,d), 8.90 (1H, s).

(b) 2-(4-Fluorophenyl)-3-hydroxy-4-methyl- [1,2,3]triazolo[1 ,5-a]quinoxalinium hydroxide, inner salt To 1 -(2-acetylamino)phenyl-3-(4-fluorophenyl)-4-hydroxy-[1,2,3]t riazolium hydroxide, inner salt (6.0g) in toluene (200ml) was added toluenesulphonic acid monohydrate (3.80g) and the mixture was heated with azeotropic removal of water (Dean and Stark conditions) for 8h. The reaction mixture was concentrated in vacuo and partitioned between dichloromethane and sodium bicarbonate solution. The organic layer was collected and dried over magnesium sulfate then concentrated in vacuo. Chromatography on silica eluting with 49:1 dichloromethane/methanol followed by recrystallization from ethyl acetate gave the title compound (1.47g) as pale yellow needles.

MS APCI (+ve) 295((M+H)+). lH NMR (CDCl3) 82.96 (3H, s), 7.23 (2H, m), 7.63 (1H, td). 7.75 (1H, td), 7.98 (H, dd), 8.18 (2H, m), 8.36 (1H, dd).

Example 105 2-(6-Chloro-3-pyridinyl)-3-hydroxy-4-methyl-[1,2,3]triazolo[ 1,5-a] quinoxalinium hydroxide, inner salt (a) 1-(2-Acetylamino)phenyl-3-(6-chloro-3-pyridinyl)-4-hydroxy-[ 1,2,3]triazolium hydroxide, inner salt.

To a solution of 5-amino-2-chloropyridine (3.0g) in water (30ml), tetrahydrofuran (lSml) and concentrated hydrochloric acid (8ml) at -5°C was added a solution of NaNOs (1.7 g) in water (lSml) dropwise maintaining a temperature of less than 0°C. Once addition was

complete the solution was stirred for a further 30min at 0°C then added portionwise to a solution of 2-(acetylamino)phenylamino acetic acid, lithium salt (5.0g) in pyridine (60ml) at -5°C maintaining a temperature of less than 0°C. The mixture was stirred at -50C for lh before being partitioned between ethyl acetate and water. The layers were separated and the aqueous was extracted with ethyl acetate. The combined organic layers were concentrated in vacuo until only pyridine remained (ca 30ml volume). To the pyridine solution was added acetic anhydride (lOml) and the solution was allowed to stir for Ih. The reaction mixture was concentrated in vacuo and azeotroped with toluene. The resulting oil was triturated with ethyl acetate to give a solid which was collected and washed with ethyl acetate to give the subtitle compound (2.2g).

MS APCI (+ve) 330/332((M+H)+). lH NMR (DMSO-d6) 6 2.02 (3H, s), 7.40 (1H, td), 7.58 (1H, s). 7.63 (2H, td), 7.70 <BR> <BR> <BR> <BR> <BR> <BR> (1H, dd), 7.76(1H, d), 7.91(1H, d), 8.54 (1H,dd), 9. 12 (1H,d), 9.78 (1H, s). <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <P>(b) 2-(6-Chloro-3-pyridinyl)-3-hydroxy-4-methyl-[1,2,3]triazolo[ 1,5-a]quinoxalinium hydroxide, inner salt To 1 -(2-acetylamino)phenyl-3-(6-chloro-3-pyridinyl)-4-hydroxy- [1 ,2,3 ]triazolium hydroxide, inner salt (5.4g) in dry acetonitrile (200ml) was added phosphorus oxychloride (2.2ml) and the mixture was heated under reflux for 3.5h. The reaction mixture was concentrated in vacuo and partitioned between ethyl acetate and sodium bicarbonate solution. The layers were separated and the aqueous extracted with ethyl acetate. The combined organic layers was washed with water and dried over magnesium sulfate then concentrated in vacuo. Chromatography on silica eluting with 49:1 dichloromethane/methanol followed by preparative HPLC afforded a gum which was dissolved in ethanol and acidified with ethereal hydrogen chloride. The solvent was reduced to low volume and the product crystallized to give the title compound (0. 14g) as pale buff crystals.

MS APCI (+ve) 312/314((M+H)+).

1H NMR (DMSO d6) # 2.80 (3H, s), 7.77 (1H, td), 7.82 (1H, d), 7.86 (1H, td), 7.98 (1H, dd), 8.45 (1H, dd), 8.63 (1H, dd), 9.22 (lH,d).

Example 106 5-(1 -Azetidinyl)-2-(6-chloropyridin-3-yl)-3-hydroxy-[1,2,3]triaz olo[1,5-a]quinolinium hydroxide, inner salt.

(a) 5-Bromo-2-(6-chloropyridin-3-yl)-3-hydroxy-[1,2,3]triazolo[1 ,5-a]quinolinium hydroxide, inner salt.

Prepared by the route of Example 30 using 2-(6-chloro-3-pyridinyl)-4,5-dihydro-3- hydroxy-[1,2,3]triazolo[1,5-a]quinolinium hydroxide, inner salt (Example 42) (l.0g) to give the subtitle compound (0.93 g) as a yellow solid. Used crude for the next step.

(b) 5-(1-Azetidinyl)-2-(6-chloropyridin-3-yl)-3-hydroxy-[1,2,3]t riazolo[1,5- a]quinolinium hydroxide, inner salt.

Prepared by the route of example 100 using crude 5-bromo-2-(6-chloropyridin-3-yl)-3- hydroxy-[1,2,3]triazolo[1,5-a]quinolinium hydroxide, inner salt (0.93g) and azetidine at 80°C in a sealed tube to give the title compound (0.050g) as an orange solid.

MS APCI (+ve) 352((M+H)+). lH NMR (CDCl3) # 2.39 (2H, quin), 4.20 (4H, t), 6.44 (1H, s), 7.79 (2H, m), 7.89 (1H, t), 8.11 (lH, d), 8.57 (1H, d), 8.74 (1H, dd), 9.30 (1H,d).

Example 107 5-(1 -Azetidinyl)-3-hydroxy-4-methyl-2-[4-(trifluoromethyl)phenyl ]-[1,2,3]triazolo[1,5- a]quinolinium hydroxide inner salt.

A solution of S -bromo-3-hydroxy-4-methyl-2- [4-(trifluoromethyl)phenyl]- [1 ,2,3]triazolo[ 1 ,5-a]quinolinium hydroxide, inner salt (0.7g), tris(dibenzylideneacetone)dipalladium (30mg), (R)-(+)-2,2-bis(diphenylphosphino)-1,1- binaphthyl (62mg), azetidine (0.34ml) and sodium tertiary butoxide (0.22g) in toluene (20ml) was heated in a sealed tube at 80°C overnight. Purification by chromatography on silica gel (dichloromethane: ethyl acetate/ 4: 1) followed by recrystallisation from ethyl acetate gave the title compound (300mg) as an orange solid.

MS APCI (+ve) 399((M+H)+).

'H NMR (DMSO d6) 8 2.30 (2H, quin), 2.69 (3H, s), 4.36 (4H, t), 7.71 (lH, t), 7.78 (1H, t), 7.79 (2H, d), 8.28 (1H, d), 8.52 (3H,m).

Example 108 2-(4-Ethylphenyl)-3-hydroxy-4-methyl-[1,2,3]triazolo[1,5-a]q uinoxalinium hydroxide, inner salt.

(a) 1 -(2-Acetylamino)phenyl-3-(4-ethylphenyl)-4-hydroxy-[1 ,2,3]triazolium hydroxide, inner salt.

Prepared as for Example 63b employing 4-ethylaniline (6.05g) and [2-(acetylamino)- phenyl]amino acetic acid, lithium salt (10.7g) to give the subtitle compound (4.3g) as a beige solid. m.p. 162-163"C MS APCI (+ve) 323 ((M+H)+).

1H NMR (CDCl3) 8 1.25 (3H, t), 2.19 (3H, s), 2.66 (2H, q), 6.90 (1H, s), 7.26 (3H, m), 7.41 (1H, dd), 7.55 (1H, td), 7.83 (2H, d), 8.32 (1H, br d), 9.17 (1H, br s).

(b) 2-(4-Ethylphenyl)-3-hydroxy-4-methyl-[1,2,3]triazolo[1,5-a]q uinoxalinium hydroxide, inner salt.

Prepared as for Example 63c employing 1-(2-acetylamino)phenyl-3-(4-ethylphenyl) -4- hydroxy-[1,2,3]triazolium hydroxide, inner salt (4.0g) to give the title compound (1.265g) as a yellow solid. m.p. 176-178"C MS APCI (+ve) 305 ((M+H)+).

lH NMR (CDCl3) 8 1.29 (3H, t), 2.73 (2H, q), 2.96 (3H, s), 7.36 (2H, d), 7.61 (1H, td), 7.72 (1H, td), 7.95 (1H, dd), 8.04 (2H, d), 8.34 (1H, dd).

Example 109 2-(3-Chlorophenyl)-3-hydroxy-4-methyl-[1,2,3]triazolo[1,5-a] quinoxalinium hydroxide, inner salt.

(a) 1-(2-Acetylamino)phenyl-3-(3-chlorophenyl)-4-hydroxy-[1,2,3] triazolium hydroxide, inner salt.

Prepared as for Example 63b employing 3-chloroaniline (2.98g) and [2-(acetylamino)- phenyl]amino acetic acid, lithium salt (5.0g) to give the subtitle compound (3.52g) as a beige solid. m.p. 187-188"C MS APCI (+ve) 329 ((M+H)+). lH NMR (CDC13) 6 2.20 (3H, s), 6.97 (1H, s), 7.29-7.40 (3H, m), 7.45 (1H, td), 7.59 (lH, td), 8.02 (1H, dd), 8.08 (1H, s), 8.37 (1H, br d), 8.68 (1H, br s).

(b) 2-(3-Chlorophenyl)-3-hydroxy-4-methyl-[1,2,3]triazolo[1,5-a] quinoxalinium hydroxide, inner salt.

Prepared as for Example 63c employing 1-(2-acetylamino)phenyl-3-(3-chlorophenyl)-4- hydroxy-[1,2,3]triazolium hydroxide, inner salt (3.32g) to give the title compound (1.265g) as an orange solid. m.p. 222-223"C

MS APCI (+ve) 311 ((M+H)+). lH NMR (CDCl3) 6 2.97 (3H, s), 7.39 (1H, dd), 7.49 (1H, t), 7.65 (1H, td), 7.76 (1H, td), 7.99 (1H, dd), 8.20 (1H, dd), 8.27 (1H, d), 8.41 (1H, dd).

Example 110 2-(4-Chlorophenyl)-3-hydroxy-4-((4-morpholinyl)methyl)-[1,2, 3]triazolo[1,5- a]quinoxalinium hydroxide, inner salt. <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <P>(a) 4-Bromomethyl-2-(4-chlorophenyl)-3-hydroxy-[1,2,3]triazolo[1 ,5-a]quinoxalinium hydroxide, inner salt.

A mixture of 2-(4-chlorophenyl)-3-hydroxy-4-methyl- [1,2,3]triazolo[l ,5-a]quinoxalinium hydroxide, inner salt (Example 57) (0. 14g), N-bromosuccinimide (0.08g) and benzoyl peroxide (3mg) was suspended in methyl formate (lOml) and dichloromethane (lOml) and heated under reflux under a nitrogen atmosphere for 16 h. The suspension was diluted with water and extracted with dichloromethane (thrice). The combined organic phases were washed with brine, dried over sodium sulfate, filtered and evaporated to leave a crude mixture of starting material, mono and dibromo compounds (0. 19g). This was used without further purification.

(b) 2-(4-Chlorophenyl)-3-hydroxy-4-((4-morpholinyl)methyl)-[1,2, 3]triazolo[1,5- a]quinoxalinium hydroxide, inner salt.

Morpholine (0.085ml) was added to a solution of the mixture obtained in (a) (0. 19g) in tetrahydrofuran (Sml). The mixture was stirred at room temperature for 30 min then diluted with water and extracted with dichloromethane (thrice). The combined organic phases were

washed with brine, dried over sodium sulfate, filtered and evaporated. The crude mixture was purified by normal phase HPLC using a Nova-Pak column, eluting with 0-5% ethanol/dichloromethane over 30 min. The resulting solid was triturated with diethyl ether to give the title compound (40mg) as a yellow solid. m.p. 224-229°C MS APCI (+ve) 396/398 ((M+H)+).

1H NMR (CDCl3) 82.82 (4H, t), 3.76 (4H, t), 4.17 (2H, s), 7.52 (2H, d), 7.68 (1H, t), 7.77 (1H, t), 8.08 (1H, d), 8.18(2H, d), 8.38 (1H, d).

Example 111 2-(3,4-Difluorophenyl)-3-hydroxy-4-(1 -imidazolyl)methyl-[1,2,3]triazolo[1,5- a]quinoxalinium hydroxide, inner salt.

(a) 4-Bromomethyl-2-[3,4-difluorophenyl)-3-hydroxy -[1,2,3]triazolo[1,5- a]quinoxalinium hydroxide, inner salt.

Prepared as for Example 129a employing 2-(3 ,4-difluorophenyl)-3-hydroxy-4-methyl- [1,2,3]triazolot1,5-a]quinoxalinium hydroxide, inner salt, (Example 64) (0.70g) to give the subtitle compound(0.58g) which was used crude for the subsequent step.

(b) 2-(3,4-Difluorophenyl)-3-hydroxy-4-(1-imidazolyl)methyl-[1,2 ,3]triazolo[1,5- a]quinoxalinium hydroxide, inner salt.

Prepared as for Example 129b employing crude 4-bromomethyl-2-(3,4-difluorophenyl)-3- hydroxy-[1,2,3]triazolo[1,5-a]quinoxalinium hydroxide, inner salt, (0.29g) to give the title compound (0.1 3g) as a yellow solid. m.p. 246-249°C MS APCI (+ve) 379 ((M+H)+). lH NMR (DMSO-d6) 6 5.71 (2H, s), 6.92 (1H, t), 7.31 (1H, t), 7.80 (4H, m), 8.09 (1H, m), 8.31(1H, m), 8.49 (lH,dd).

Example 112 3-Hydroxy-4-methyl-2-(4-trifluoromethoxyphenyl)-[1,2,3]triaz olo[1,5- a]quinoxalinium hydroxide, inner salt.

(a) 1-(2-Acetylamino)phenyl-4-hydroxy-3-(4-trifluoromethoxypheny l)- [1,2,3] triazolium hydroxide, inner salt.

Prepared as for Example 63b employing 4-trifluoromethoxyaniline (9.6g) and [2- (acetylamino)phenyl]amino acetic acid, lithium salt (Example 63a, 10g) to give the subtitle compound (2.8g).

MS APCI (+ve) 379 ((M+H)+).

(b) 3-Hydroxy-4-methyl-2-(4-trifluoromethoxyphenyl)-[1,2,3]triaz olo[1,5- a]quinoxalinium hydroxide, inner salt.

Prepared as for Example 63c employing 1-(2-acetylamino)phenyl-4-hydroxy-3-(4- trifluoromethoxy)-[1,2,3]triazolium hydroxide, inner salt (2.8g) to give the title compound (0.65g) as a yellow solid. m.p. 205°C MS APCI (+ve) 361 ((M+H)+).

1H NMR (CDCl3) 6 2.97 (3H, s), 7.41 (2H, d), 7.65 (1H, t+fine), 7.76 (1H, td), 7.99 (1H, d+fine), 8.25-8.31 (2H, m), 8.37 (1H, d+ fine).

Example 113 2-(4-Fluoro-3-methyl)phenyl-3-hydroxy-4-methyl-[1,2,3]triazo lo[1 ,5-a]quinoxalinium hydroxide, inner salt.

(a) 1-(2-Acetylamino)phenyl-4-hydroxy-3-(4-fluoro-3-methylphenyl )-[1,2,3]triazolium hydroxide, inner salt.

Prepared as for Example 63b employing 4-fluoro-3-methylaniline (6.3g) and [2- (acetylamino)-phenyl]amino acetic acid, lithium salt (10.7g) to give the subtitle compound (2.4g) as a buff solid. m.p. 201-202°C MS APCI (+ve) 327 ((M+H)+).

1H NMR (CDCl3) # 2.20 (3H, s), 2.29 (3H, d), 6.95 (1H, s), 7.06 (1H, t), 7.29 (1H, m),<BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> 7.44 (1H, dd), 7.57 (1H, td), 7.80 (2H, d), 8.34 (1H, br d), 8.97 (1H, br s).

(b) 2-(4-Fluoro-3-methyl)phenyl-3-hydroxy-4-methyl-[1,2,3]triazo lo[1,5- a]quinoxalinium hydroxide, inner salt.

Prepared as for Example 63c employing 1-(2-acetylamino)phenyl-4-hydroxy-3-(4-fluoro-3- methylphenyl)-[1,2,3]triazolium hydroxide, inner salt (6.6g) to give the title compound (1.00g) as a yellow solid. m.p. 203-205°C MS APCI (+ve) 309 ((M+H)+).

H NMR (CDCl3) 82.39 (3H, s), 2.96 (3H, s), 7.17 (1H, t), 7.63 (1H, td), 7.74 (1H, td), 7.94 (1H, m), 7.97 (1H, dd), 8.05 (1H, dd), 8.36 (1H, dd).

Example 114 2-(3-Fluoro-4-methyl)phenyl-3-hydroxy-4-methyl- [1,2,3] triazolo[1 ,5-a]quinoxalinium hydroxide, inner salt.

(a) 1-(2-Acetylamino)phenyl-4-hydroxy-3-(3-fluoro-4-methylphenyl )-[1,2,3]triazolium hydroxide, inner salt.

Prepared as for Example 63b employing 3-fluoro-4-methylaniline (1.75g) and [2- (acetylamino)-phenyl]amino acetic acid, lithium salt (3.0g) to give the crude subtitle compound which was used crude for the subsequent step.

(b) 2-(3-Fluoro-4-methyl)phenyl-3-hydroxy-4-methyl- [1,2,3]triazolo[1,5-a]- quinoxalinium hydroxide, inner salt.

Prepared as for Example 63c employing crude 1-(2-acetylamino)phenyl-4-hydroxy-3-(3- fluoro-4-methyl)phenyl-[1,2,3]triazolium hydroxide, inner salt to give the title compound (0.181g) as a yellow solid. m.p. 213-214"C MS APCI (+ve) 309 ((M+H)+). lH NMR (CDCl3) 6 2.35 (3H, d), 2.96 (3H, s), 7.35 (lH, t), 7.63 (lH, td), 7.75 (lH, td), 7.96 (3H, m), 8.37 (1H, dd).

Example 115 3-Hydroxy-4-methyl-2-(4-methylthiophenyl)-[1,2,3]triazolo[1, 5-a]quinoxalinium hydroxide, inner salt.

(a) 1-(2-Acetylamino)phenyl-4-hydroxy-3-(4-methylthiophenyl)-[1, 2,3]triazolium hydroxide, inner salt.

Prepared as for Example 63b employing 4-methythiolaniline (1.74ml) and [2- (acetylamino)-phenyl]amino acetic acid, lithium salt (3.0g) to give the crude subtitle compound which was used crude for the subsequent step.

(b) 3-Hydroxy-4-methyl- 2-(4-methylthiophenyl)-[1,2,3]triazolo[1,5-a]quinoxalinium hydroxide, inner salt.

Prepared as for Example 63c employing crude 1 -(2-acetylamino)phenyl-4-hydroxy-3-(4- methylthiophenyl)-[1,2,3]triazolium hydroxide, inner salt to give the title compound (0.99g) as a yellow solid. m.p. 198-199"C MS APCI (+ve) 323 ((M+H)+). lH NMR (CDCl3) 82.55 (3H, s), 2.96 (3H, s), 7.40 (2H, d), 7.63 (1H, td), 7.74 (1H, td), 7.98(1H, dd), 8.12 (2H,d), 8.36 (1H, dd).

Examples 116-122 Examples 116-122 were prepared on a Bodan reaction station using the following general method.

The aromatic anilines were dissolved in tetrahydrofuran to a 1 molar solution. 1 ml was then transferred to 1.9 ml of 4 M hydrochloric acid and the mixture cooled to -50C. lml of a 1 molar solution of sodium nitrite was then added and mixing achieved by bubbling argon through the mixture for 20 seconds. After a further 20 minutes each diazonium salt was transferred to a mixture of [2-(acetylamino)phenyl]amino acetic acid, lithium salt (Example 63a) (0.2g) in pyridine and the mixture stirred under vortex. After approximately 1 hour each reaction was quenched with water and extracted with ethyl acetate. The ethyl acetate was removed in a centrifuge evaporator. The residues were then redissolved in pyridine (2 ml ) and acetic anhydride (0.2 ml) was added and the solution left standing overnight. The solvent was again removed in a centrifuge evaporator and the residue transferred to reactions tube suitable for heating at reflux. This material was dissolved in acetic acid and toluenesulphonic acid (0.2 g) was added. The mixture was heated at reflux for 16 hours where upon the solvent was removed and the residue purified by normal phase HPLC using dichloromethane/ ethanol gradient to provide samples of the following.

Example 116 3-Hydroxy-4-methyl-2-(6-quinolyl)-[1,2,3]triazolo[1,5-a]quin oxalinium hydroxide, inner salt di (p-toluenesulfonate). m.p. 266-270°C MS APCI (+ve) 328 ((M+H)+). lH NMR (DMSO-d6) # 2.98 (3H, s), 7.76 (1H, s), 7.85 (1H, td), 8.02 (2H, br m), 8.50 (lH, dd), 8.56 (lH, d), 8.87 (lH, dd), 9.03 (lH, br d), 9.30 (2H, m).

Example 117 3-Hydroxy-4-methyl-2-(3-quinolyl)-[1,2,3]triazolo[1,5-a]quin oxalinium hydroxide, inner salt di (p-toluenesulfonate). m.p. 175-179°C MS APCI (+ve) 328 ((M+H)+).

Example 118 3-Hydroxy-4-methyl-2-(4-trifluoromethylthiophenyl)-[1,2,3]tr iazolo[1,5- a]quinoxalinium hydroxide, inner salt p-toluenesulfonate. m.p. 192-194°C MS APCI (+ve) 377 ((M+H)+). lH NMR (CDCl3) # 3.22 (3H, s), 7.94 (4H, m), 8.23 (2H, d), 8.42 (1H, dd), 8.60 (1H, dd).

Example 119 2-(3-Chloro-4-methylphenyl)-3-hydroxy-4-methyl-[1,2,3]triazo lo[1,5-a]quinoxalinium hydroxide, inner salt p-toluenesulfonate. m.p. 231-233°C MS APCI (+ve) 325/7 ((M+H)+). lH NMR (CDCl3) 8 2.37 (3H, s), 2.48 (3H, s ), 3.20 (3H, s), 7.21 2H, d ), 7.45 (1H, d), 7.81-7.95 (6H, m), 8.09 (1H, d), 8.41 (1H, dd), 8.57 (1H, d).

Example 120 2-(4-Cyclohexylphenyl)-3-hydroxy-4-methyl-[1,2,3]triazolo[1, 5-a]quinoxalinium hydroxide, inner salt p-toluenesulfonate. m.p. 231-5°C MS APCI (+ve) 359 ((M+H)+). lH NMR (CDC13) 6 1.1-1.9 (10H, m), 2.38 (3H, s ), 2.63 (1H, m), 3.22 (3H, s), 7.21-7.31 (3H, m ), 7.44 (2H, d), 7.80-7.94 (SH, m), 8.40 (1H, d), 8.62 (1H, d).

Example 121 3-Hydroxy-2-(4-isopropylphenyl)-4-methyl-[1,2,3]triazolo[1,5 -a]quinoxalinium hydroxide, inner salt p-toluenesulfonate. m.p. 163-4°C MS APCI (+ve) 319 ((M+H)+).

Example 122 3-Hydroxy-4-methyl-2-(3-methylphenyl)-[1,2,3]tH.azolo[1,5a]q uinoxalinium hydroxide, inner salt p-toluenesulfonate. m.p. 202-6°C MS APCI (+ve) 291 ((M+H)+). lH NMR (CDCl3) 6 2.38 (3H, s), 2.50 ( 3H, s ), 3.23 (3H, s), 7.25 ( 2H, d ), 7.34 (1H, d), 7.49 (1H, t), 7.83-7.94 (6H, m), 8.41 (1H, d+fine), 8.63 (1H, d).

Example 123 3-Hydroxy-5-methylsulfonylamino-2-(4-trifluoromethoxyphenyl) -[1,2,3]triazolo[1,5- a]quinolinium hydroxide, inner salt.

(a) 3-Hydroxy-5-nitro-2-(4-trifluoromethoxyphenyl)-[1,2,3]triazo lo[1,5-a]quinolinium hydroxide, inner salt.

Prepared as for Example 51 employing 3-hydroxy-2-(4-trifluoromethoxyphenyl)- [1,2,3]triazolo[1,5-a]quinolinium hydroxide, inner salt (Example 37) (11.39g) and 1.0M nitronium tetrafluoroborate in sulfolane (70ml) to give the subtitle compound (10.5g) as an orange solid.

MS APCI (+ve) 391 ((M+H)+).

(b) 5-Amino-3-hydroxy-2-(4-trifluoromethoxyphenyl)-[1,2,3]triazo lo[1,5- a]quinolinium hydroxide, inner salt.

Prepared as for Example 60 employing 3-hydroxy-5-nitro-2-(4-trifluoromethoxyphenyl)- [1,2,3]triazolo[1,5-a]quinolinium hydroxide, inner salt (10.0g) to give the subtitle compound as a yellow solid.

MS APCI (+ve) 361 ((M+H)+).

(c) 3-Hydroxy-5-methylsulfonylamino-2-(4-trifluoromethoxyphenyl) - [1,2,3]triazolo[l,5-a]quinolinium hydroxide, inner salt.

Prepared as for Example 128 employing S-amino-2-(4-trifluoromethoxyphenyp-3-hydroxy- [1 ,2,3]triazolo [1 ,5-a]quinolinium hydroxide, inner salt (1.0g) and methanesulfonyl chloride (0.86ml) to give the title compound (0.6g) as a yellow solid. m.p. 286-288°C MS APCI (+ve) 439 ((M+H)+). lH NMR (DMSO-d6) 8 3.14 (3H, s), 7.58 (1H, s), 7.64 (2H, d), 7.90 (2H, m),8.30 (1H, dd), 8.37 (2H, d), 8.57 (1H, dd), 10.00 (lH, s).

Example 124 3-Hydroxy-4-((4-morpholinyl)methyl)- 2-(4-trifluoromethoxyphenyl)- [1,2,3]triazolo[l,5-a]quinoxalinium hydroxide, inner salt.

(a) 4-Bromomethyl-3-hydroxy-2-(4-trifluoromethoxyphenyl)-[1,2,3] triazolo[1,5- a]quinoxalinium hydroxide, inner salt.

A mixture of 3-hydroxy-4-methyl-2-(4-trifluoromethoxyphenyl)- [1 ,2,3]triazolo [1,5- a]quinoxalinium hydroxide, inner salt (Example 112) (2.35g), N-bromosuccinimide (3.0g) and benzoyl peroxide (lOmg) was suspended in methyl formate (SOml) and dichloromethane (SOml) and heated under reflux while being irradiated using a UV lamp for 16 h. The suspension was diluted with water and extracted with dichloromethane (thrice). The combined organic phases were washed with saturated aqueous sodium metabisulfite solution and brine, dried over sodium sulfate, filtered and evaporated.

Chromatography on silica eluting with dichloromethane gave the crude dibromo compound. This intermediate was dissolved in tetralin (20ml) and warmed to 950C for 30minutes. After allowing to cool to room temperature the mixture was poured directly onto a flash silica chromatography column, eluting initially with dichloromethane to remove the tetralin and related products then with 200:1 dichloromethane/:methanol to give the subtitle compound as a yellow solid (1.1 lg).

MS APCI (+ve) 439 ((M+H)+). lH NMR (CDC13) 6 4.97 (2H, s), 7.41 (2H, d), 7.73 (1H, td), 7.81 (1H, td), 8.07 (1H, dd), 8.30 (2H, d), 8.408 (1H, dd).

(b) 3-Hydroxy-4-((4-morpholinyl)methyl)-2-(4-trifluoromethoxyphe nyl)- [1,2,3]triazolo[l,5-a]quinoxalinium hydroxide, inner salt.

Morpholine (0.2ml) was added to a solution of 4-bromomethyl-3-hydroxy-2-(4- trifluoromethoxyphenyl)-[1,2,3]triazolo[1,5-a]quinoxalinium hydroxide, inner salt (0.Sg) in tetrahydrofuran (lOml). The mixture was stirred at room temperature for 30 min then diluted with water and extracted with dichloromethane (thrice). The combined organic phases were washed with brine, dried over sodium sulfate, filtered and evaporated.

Chromatography on silica eluting with 50:1 dichloromethane/methanol, followed by trituration with diethyl ether gave the title compound (0.09g) as a yellow solid. m.p. 181-182"C MS APCI (+ve) 446 ((M+H)+). lH NMR (CDCl3) 6 2.82 (4H, t), 3.76 (4H, t), 4.17 (2H, s), 7.402 (2H, d), 7.69 (1H, td), 7.78 (lH, td), 8.09 (1H, dd), 8.27 (2H, d), 8.39 (1H, dd).

Example 125 3-Hydroxy-4-(imidazo1- l-yl)methyl-2-(4-trifluoromethoxyphenyl)- [1,2,3]triazolo [1,5- a]quinoxalinium hydroxide, inner salt.

Prepared as for Example 124b employing 4-bromomethyl-3-hydroxy-2-(4- trifluoromethoxypheny1)-[ 1,2,3]triazolo[l ,5-a]quinoxalinium hydroxide, inner salt (Example 124a) (0.25g) and imidazole (0.077g) to give the title compound (0.15g) as a yellow solid.

m.p. 249-253"C MS APCI (+ve) 427 ((M+H)+). lH NMR (CDCl3) 6 5.69 (2H, s), 7.05 (1H, s), 7.32 (1H, s), 7.42 (2H, d), 7.73 (1H, td), 7.81(1H, td), 7.92 (1H, s), 8.05 (1H, dd), 8.24 (2H, d), 8.38 (1H, dd).

Example 126 3-Hydroxy-4-(piperazinyl)methyl-2-(4-trifluoromethoxyphenyl) -[1,2,3]triazolo[1,5- a]quinoxalinium hydroxide, inner salt dihydrochloride.

(a) 4-((4-[1,1-Dimethylethyl]oxycarbonyl)piperazinyl)methyl-3-hy droxy-2-(4- trifluoromethoxypheny1) -[1,2,3]triazolo[l ,5-a] quinoxalinium hydroxide, inner salt.

Prepared as for Example 124b employing 4-bromomethyl-3-hydroxy-2-(4- trifluoromethoxyphenyl)- [1,2,3 ]triazolo [1 ,5-a]quinoxalinium hydroxide, inner salt (Example 124a) (0.3g) and l-t-butoxycarbonylpiperazine (0.32g) to give the subtitle compound (0.24g) as a yellow solid. m.p. 169-170°C MS APCI (+ve) 545 ((M+H)+). lH NMR (CDCl3) 6 1.45 (9H, s), 2.76 (4H, t), 3.48 (4H, t), 4.19 (2H, s), 7.41 (2H, d), 7.69 (1H, td), 7.78 (1H, td), 8.09 (1H, d), 8.26 (2H, d), 8.39 (1H, dd).

(b) 3-Hydroxy-4-(piperazinyl)methyl-2-(4-trifluoromethoxyphenyl) - [1,2,3]triazolo[1,5-a]quinoxalinium hydroxide, inner salt dihydrochloride.

A solution of 4-((4-[1,1-dimethylethyl]oxycarbonyl)piperazinyl)methyl-3-hy droxy-2-(4- trifluoromethoxyphenyl)- [1 ,2,3]triazolo[ 1 ,5-a]quinoxalinium hydroxide, inner salt (0.26g)

in dichloromethane (Sml) and trifluoroacetic acid (5ml) was stirred at room temperature for 30 minutes. The solvent was removed in vacuo and the residue was suspended in methanol (5ml) and a 1.OM solution of hydrochloric acid in diethyl ether (5ml) was added, the solvent was then removed. This was repeated a further two times. The resulting solid was triturated with ethyl acetate and collected by filtration then washed with diethyl ether to give the title compound as a yellow solid (0.236g).

MS APCI (+ve) 445 ((M+H)+). lH NMR (DMSO-d6) 6 3.31 (8H, br s), 4.60 (2H, br s), 7.68 (1H, d), 7.91 (2H, m), 8.11 (1H, dd), 8.31 (2H, m), 8.51 (1H, dd).

Example 127 4-Aminomethyl-3-hydroxy-2-(4-trifluoromethoxyphenyl)- [1,2,3]triazolo[1,5- a]quinoxalinium hydroxide, inner salt dihydrochloride.

Aqueous 880 ammonia (7ml) was added to a solution of 4-bromomethyl-3-hydroxy-2-(4- trifluoromethoxyphenyl)-[1,2,3]triazolo[1,5-a]quinoxalinium hydroxide, inner salt (Example 124a, 0.25g) in tetrahydrofuran (20ml) and the mixture was stirred at room temperature for 1 hour. The solution was diluted with water and extracted with dichloromethane (thrice). The combined organic phases were washed with brine, dried over sodium sulfate, filtered and evaporated. Chromatography on silica eluting with 20:1 dichloromethane/methanol gave the title compound as the free base. Treatment of the free base with tetrahydrofuran (Sml) and 1.OM hydrochloric acid in diethyl ether (2ml) yielded a blue/green solid which was collected by filtration then washed well with methanol, ethyl acetate and diethyl ether (0.037g).

m.p. 277-280°C MS APCI (+ve) 376 ((M+H)+). lH NMR (DMSO-d6) 6 4.65 (2H, s), 7.67 (2H, d), 7.92 (2H, m), 8.12 (1H, dd), 8.25 (2H, d), 8.52 (1H, dd).

Example 128 3-Hydroxy-5-(1-methylimidazol-4-yl)sulfonylamino-2-(4-triflu oromethoxyphenyl)- [1,2,3]triazolo[1,5-a]quinolinium hydroxide, inner salt.

5-Amino-3-hydroxy-2-(4-trifluoromethoxyphenyl)-[1,2,3]tri azolo[1,5-a]quinolinium hydroxide, inner salt (Example 123b) (0.36g) and 1-methylimidazole-4-sulfonyl chloride (0.2g) were suspended in pyridine (20ml) and stirred at room temperature for 16 hours. 2M Hydrochloric acid was added and the aqueous phase was extracted with dichloromethane (thrice). The organic phases were combined and the solvent removed. Chromatography on silica eluting with SO: 1 dichloromethane/methanol followed by trituration with ethyl acetate gave the title compound (0.18g) as a yellow solid. m.p. >300°C MS APCI (+ve) 505 ((M+H)+). lH NMR (DMSO-d6) # 3.62 (3H, s), 7.43 (1H, s), 7.63 (2H, d), 7.77 (1H, s), 7.81 (2H, m), 7.87 (1H, td), 8.22 (1H, d), 8.34 (2H, d), 8.52 (1H, dd), 10.45 (1H, s).

Example 129 2-(4-Fluorophenyl)-3-hydroxy-4-(imidazol-1 -yl)methyl-[1 ,2,3]triazolo[1,5- a]quinoxalinium hydroxide, inner salt. <BR> <BR> <BR> <BR> <BR> <BR> <P>(a) 4-Bromomethyl-2-(4-fluorophenyl)-3-hydroxy-[1,2,3]triazolo[1 ,5-a]quinoxalinium hydroxide, inner salt.

A mixture of 2-(4-fluorophenyl)-3-hydroxy-4-methyl-[1,2,3]triazolo[1,5-a] quinoxalinium hydroxide, inner salt (Example 104) (1.7g), pyridine (0.56ml) and bromine (0.36ml) in dichloromethane (50ml) was stirred at room temperature for 1 hour. The mixture was diluted with water and extracted with dichloromethane (thrice). The organic phases were combined and dried over sodium sulfate, filtered and evaporated to give the dibromide as the major product. At this stage a small amount of the monobromo could be obtained by chromatography (silica, 100:1 dichloromethane/methanol). The dibromide was suspended in tetralin (l5ml) and warmed to 1450C for minutes. After allowing to cool to room temperature the mixture was poured directly onto a flash silica chromatography column, eluting initially with dichloromethane to remove the tetralin and related products then with 100:1 dichloromethane/:methanol to give the subtitle compound as a yellow solid (1.83g).

MS APCI (+ve) 373 ((M+H)+).

(b) 2-(4-Fluorophenyl)-3-hydroxy-4-(imidazol-1-yl)methyl-[1,2,3] triazolo[1,5- a]quinoxalinium hydroxide, inner salt.

Prepared as for Example 124b employing 4-bromomethyl-2-(4-fluorophenyl)-3-hydroxy- [1,2,3]triazolo[1,5-a]quinoxalinium hydroxide, inner salt (0.4g) and imidazole (0.1 lg) to give the title compound (0.165g) as a yellow solid. m.p. 256-258"C MS APCI (+ve) 361 ((M+H)+). lH NMR (CDCl3) 6 5.69 (2H, s), 7.05 (1H, s), 7.27 (3H, m), 7.71 (1H, td), 7.79 (1H, td), 7.93 (1H, s), 8.04 (1H, dd), 8.15 (2H, m), 8.378 (1H, dd).

Example 130 2-(3-Fluoro-4-methoxyphenyl)-3-hydroxy-4-methyl-[1,2,3]triaz olo[1,5-a]- quinoxalinium hydroxide, inner salt To a solution of 3-fluoro-4-methoxyaniline (1.96g) in water (20ml), tetrahydrofuran (l0ml) and concentrated hydrochloric acid (Sml) at -5°C, was added a solution of NaNO2 (1.02g) in water (10ml) dropwise maintaining a temperature of less than 0°C. Once addition was complete the solution was stirred for a further 15min at 0°C then added portionwise to a solution of 2-(acetylamino)phenylamino acetic acid, lithium salt (Example 63a) (3.0g) in pyridine (25ml) at -50C maintaining a temperature of less than 0°C. The mixture was stirred at 0°C for lh before being partitioned between ethyl acetate and water. The organic layer was collected and dried over magnesium sulfate then concentrated in vacuo until only pyridine remained (ca lOml volume). To the pyridine solution was added acetic anhydride (5ml) and the solution was allowed to stir for 14h. The reaction mixture was concentrated

in vacuo and azeotroped with toluene to give a dark red solid. The solid was heated with toluenesulphonic acid (2.7g) in toluene (120ml) for 1 8h at reflux with azeotropic removal of water. The cooled solution was partitioned between aqueous sodium bicarbonate solution and ethyl acetate. The organic extracts were concentrated in vacuo and chromatographed on silica (chloroform : ethyl acetate, 2:1) and recrystallized from ethanol : tetrahydrofuran to give the title compound as fawn needles (0.35g) m.p 242-244"C MS APCI (+ve) 325 ((M+H)+). lH NMR (DMSO-d6) 6 2.78 (3H, s), 3.94 (3H,s), 7.43 (1H, t), 7.77 (1H, t),. 7.94 (lH,s), 7.97 (2H,d), 8.05 (lH,dd), 8.44 (lH,d) Example 131 3-Hydroxy-5-nitro-2-(4-methylphenyl)- [1,2,3]triazolo[1,5-a] quinoxalinium hydroxide, inner salt.

3-Hydroxy-2-(4-methylphenyl)- [1 ,2,3]triazolo [1 ,5-a]quinolinium hydroxide, inner salt (Example 34) (5.7g) was dissolved in dichloromethane (400ml) followed by portionwise addition of 0.5M nitronium tetrafluoroborate in sulfolane (45ml) during 10 minutes at room temperature. The reaction was complete after a further 10 minutes and was poured into aqueous sodium hydrogen solution, shaken and the organic layer separated and shaken with water twice. Concentration in vacuo yielded a solid which was rinsed further with water and collected by filtration to give the title compound as orange crystals (5.0g). m.p 243-245"C

MS APCI (+ve) 321 ((M+H)+).

1H NMR (DMSO-d6) 6 2.41 (3H, s), 7.44 (2H, d), 7.96 (4H, m),. 8.04 (2H,d), 8.61 (1H, s), 8.67 (3H,m).

Example 132 3-Hydroxy-5-methanesulfonamido-2-(4-methylphenyl)-[1,2,3]tri azolo[1,5- a]quinoxalinium hydroxide, inner salt.

(a) 5-Amino-3-hydroxy-2-(4-methylphenyl)-[1,2,3]triazolo[1,5-a]q uinoxalinium hydroxide, inner salt.

3-Hydroxy-5-nitro-2-(4-methylphenyl)- [1 ,2,3]triazolo [1 ,5-a]quinoxalinium hydroxide, inner salt (Example 131) (5.0g) was suspended in tetrahydrofuran (400ml) and hydrogenated at S bar using 10% palladium on carbon (0.Sg) as catalyst. The mixture was filtered through Celite, the filtrate evaporated to dryness under reduced pressure and the residue triturated with ethanol to give the subtitle compound as a brown solid (1.6g). m.p 261-264"C MS APCI (+ve) 291 ((M+H)+).

1H NMR (DMSO-d6) # 2.49 (3H, s), 6.28 (2H, s), 7.36 (2H, d),. 7.81 (1H,dt), 7.88 (1H, t), 8.14 (2H,d), 8.28 (lH,d), 8.52 (lH,d).

LAb 3-Hydroxy-5-methanesulfonamido-2-(4-methylphenyl)-[1,2,3]tri azolo[1,5- a]quinoxalinium hydroxide, inner salt.

5-Amino-3-hydroxy-2-(4-methylphenyl)-[l ,2,3]triazolo[l ,5-a]quinoxalinium hydroxide, inner salt (0.5g) was dissolved in dry pyridine (80ml) followed by addition of methanesulfonyl chloride (0.44g) and the whole stirred at room temperature overnight.

The mixture was poured into water and extracted three times with ethyl acetate, the combined extracts concentrated by reduced pressure and the residue dissolved in tetrahydrofuran (500ml) followed by addition of 2M sodium hydroxide (100ml). After stirring at room temperature overnight the mixture was neutralised with lOM hydrochloric acid then concentrated by reduced pressure. The residue was partitioned between ethyl acetate and water, the organic layer separated and evaporated under reduced pressure to give a solid. This was recrystallised from ethanol twice to give the title compound as a yellow-brown powder (0.32g). m.p 244-246"C MS APCI (+ve) 369 ((M+H)+). lH NMR (DMSO-d6) 82.40 (3H, s), 3.12 (3H,s), 7.41 (2H, d), 7.56 (1H, s),. 7.87 (2H,m), 8.08 (2H,d), 8.28 (lH,d), 8.57 (lH,d), 9.96 (lH,s).

Example 133 3-Hydroxy-4-methyl-2-(4-methylphenyl)-5-nitro- [1,2,3]triazolo[1,5-a]quinoxalinium hydroxide, inner salt.

Prepared from 3-hydroxy-4-methyl-2-(4-methylphenyl)-[ 1,2,3]triazolo[1,5- a]quinoxalinium hydroxide, inner salt following the procedure of Example 131. m.p 223-225"C MS APCI (+ve) 335 ((M+H)+). lH NMR (DMSO-d6) 8 2.40 (3H, s), 2.72 (3H,s), 7.44 (2H, d), 7.87 (3H, m),. 8.02 (2H, d), 8.56 (lH,d).

Example 134 2-(4-Fluorophenyl)-3-hydroxy-5-methylsulphonylamino-[1,2,3]t riazolo[1,5- a]quinolinium hydroxide, inner salt.

Prepared as for Example 128 employing 5-amino-2-(4-fluorophenyl)-3-hydroxy- [1 ,2,3]triazolo [1 ,5-a]quinolinium hydroxide, inner salt (Example 60) (0.50g) and methanesulphonyl chloride (0.32ml) to give the title compound (0.29g) as a yellow solid. m.p. 283-285"C MS APCI (+ve) 373 ((M+H)+). lH NMR (DMSO-d6) 8 3.13 (3H, s), 7.48 (2H, m), 7.57 (1H, s), 7.88 (2H, m), 8.23 (2H, m), 8.30(1H, dd), 8.57 (1H,dd), 9.98 (1H, s).

Example 135 2-(4-Fluorophenyl)-3-hydroxy-5-(1 -methylimidazol-4-yl)sulphonylamino- [1,2,3]triazolo[l,5-a]quinolinium hydroxide, inner salt.

Prepared as for Example 128 employing 5-amino-2-(4-fluorophenyl)-3-hydroxy- [1,2,3]triazolo[1,5-a]quinolinium hydroxide, inner salt (Example 60) (0.29g) and methylimidazolesulphonyl chloride (0.20g) to give the title compound (0.22g) as a yellow solid. m.p. 299-3010C MS APCI (+ve) 439 ((M+H)+).

1H NMR (DMSO-d6) # 3.61 (3H, s), 7.41 (1H, s), 7.46 (2H, t), 7.81 (4H, m), 8.22 (3H, m), 8.51 (1H, dd), 10.42 (lH,bs).

Example 136 2-(4-Fluorophenyl)-3-hydroxy-5-(3-pyridinyl)sulphonylamino-[ 1,2,3]triazolo[1,5- a]quinolinium hydroxide, inner salt.

Prepared as for Example 128 employing 5-amino-2-(4-fluorophenyl)-3-hydroxy- [1,2,3]triazolo[1,5-a]quinolinium hydroxide, inner salt (Example 60) (0.40g) and 3- pyridinesulphonyl chloride (0.30g) to give the title compound (0.31g) as a yellow solid. m.p. 249-2540C MS APCI (+ve) 436 ((M+H)+).

1H NMR (DMSO-d6) # 7.20 (1H, s), 7.46 (2H, t), 7.56 (1H, m), 7.70 (1H, td), 7.83 (1H, td), 7.96(1H, d), 8.14 (1H, dt), 8.21 (2H, m), 8.51 (1H, d), 8.78 (1H, dd), 8.90(1H, d), 10.75 (1H, bs).

Pharmacological Data Test A - Chronic graft-versus-host test Pharmacological activity of the compounds of the invention may be demonstrated using the method of J M Doutrelepont et al ([Clin Exp Immunol, 1991, vol 83, 133-6; Inhibition of chronic graft-versus-host (c-GVH) disease in the mouse]. Test compound was administered to mice subcutaneously as a suspension in saline with TWEEN-80 every day for 21 days.

Test B - Inhibition of Eosinophilia The effects of the compounds of the invention on inflammatory cells in mouse lungs was assessed by the following method, adapted from Brusselle et al , Clin. Exp. Allergy 1994, 24, 73-80. The measurement of eosinophil peroxidase as a marker for eosinophil numbers was adapted from Cheng et al, J. Pharmacol Exp. Ther. 1993, 264, 922-929.

Male Balb/c mice were administered an ovalbumin/Al(OH)3 mixture and were allowed to sensitise for at least fourteen days. After the period of sensitisation mice were placed into perspex chambers into which a solution of ovalbumin (2%w/v) was nebulised. The mice were able to inhale the ovalbumin for a period of 30-40min. The inhalation challenge with ovalbumin was repeated daily for 4 or 8 consecutive days. Compounds were administered in 5% Tween 80 either orally or subcutaneously as a suspension or solution (depending on dose and compound solubility) at least lhr before each daily inhalation challenge. Twenty four hours after the final inhalation challenge the mice were sacrificed and the inhibition of the following parameters was measured by comparison to control animals: (1) Increase in the numbers of inflammatory cells in the bronchioalveolar lavage, in particular eosinophils (after the 4 day dosing).

(2) Accumulation of eosinophils within lung tissue, as measured by the increase in eosinophil peroxidase activity in homogenised lung tissue (after the 8 day dosing).

(3) Increase in antibody titres (IgE, IgG1 and IgG2a) present in the serum obtained from whole blood (after the 8 day dosing).

Test C - Inhibition of Eosinophilia Female Brown Norway rats were administered an ovalbumin/Al(OH)3 mixture and allowed to sensitise for at least fourteen days. After the period of sensitisation the rats were placed into perspex chambers into which a solution of ovalbumin (1%w/v) was nebulised. The rats were able to inhale the ovalbumin for a period of 15 min. Compounds were administered in a suitable vehicle either orally or subcutaneously as a suspension or solution (depending on dose and compound solubility) at least lhr before and 24hr after inhalation challenge with ovalbumin. Forty eight hours after the inhalation challenge the rats were sacrificed, the lungs lavaged and the inhibition of eosinophil infiltration into the lavage determined.

The compounds of the invention show activities in the chronic graft versus host test and the inhibition of eosinophilia tests with EDsoss in the range of 0.1 - 10 mg/kg.