Novel compounds

Compounds of formula (I): ##STR1## or a tautomeric form thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, wherein: PA1 A.sup.1 represents a substituted or unsubstituted aromatic heterocyclyl group; PA1 R.sup.1 represents a hydrogen atom, an alkyl group, an acyl group, an aralkyl group, wherein the aryl moiety may be substituted or unsubstituted, or a substituted or unsubstituted aryl group; PA1 R.sup.2 and R.sup.3 each represent hydrogen, or R.sup.2 and R.sup.3 together represent a bond; PA1 A.sup.2 represents a benzene ring having in total up to five substituents; and PA1 n represents an integer in the range of from 2 to 6; pharmaceutical compositions containing such compounds and the use of such compounds and compositions in medicine.

This invention relates to certain substituted thiazolidinedione 
derivatives, to a process for preparing such compounds, to pharmaceutical 
compositions containing such compounds and to the use of such compounds 
and compositions in medicine. 
European Patent Applications, Publication Numbers 0008203, 0139421, 
0155845, 0177353, 0193256, 0207581 and 0208420 relate to thiazolidinedione 
derivatives which are disclosed as having hypoglycaemic and hypolipidaemic 
activity. Chem. Pharm. Bull 30 (10) 3580-3600 also relates to certain 
thiazolidinedione derivatives having hypoglycaemic and hypolipidaemic 
activities. 
It has now surprisingly been discovered that certain novel 
substituted-thiazolidinedione derivatives show improved blood-glucose 
lowering activity and are therefore of potential use in the treatment 
and/or prophylaxis of hyperglycaemia and are of particular use in the 
treatment of Type II diabetes. 
These compounds are also indicated to be of potential use for the treatment 
and/or prophylaxis of other diseases including hyperlipidaemia, 
hypertension, cardiovascular disease and certain eating disorders. 
Accordingly, the present invention provides a compound of formula (I): 
##STR2## 
or a tautomeric form thereof and/or a pharmaceutically acceptable salt 
thereof, and/or a pharmaceutically acceptable solvate thereof, wherein: 
A.sup.1 represents a substituted or unsubstituted aromatic heterocyclyl 
group; 
R.sup.1 represents a hydrogen atom, an alkyl group, an acyl group, an 
aralkyl group, wherein the aryl moiety may be substituted or 
unsubstituted, or a substituted or unsubstituted aryl group; 
R.sup.2 and R.sup.3 each represent hydrogen, or R.sup.2 and R.sup.3 
together represent a bond; 
A.sup.2 represents a benzene ring having in total up to five substituents; 
and 
n represents an integer in the range of from 2 to 6. 
Suitable aromatic heterocyclyl groups include substituted or unsubstituted, 
single or fused ring aromatic heterocyclyl groups comprising up to 4 
hetero atoms in each ring selected from oxygen, sulphur or nitrogen. 
Favoured aromatic heterocyclyl groups include substituted or unsubstituted 
single ring aromatic heterocyclyl groups having 4 to 7 ring atoms, 
preferably 5 or 6 ring atoms. 
In particular, the aromatic heterocyclyl group comprises 1, 2 or 3 
heteroatoms, especially 1 or 2, selected from oxygen, sulphur or nitrogen. 
Suitable values for A.sup.1 when it represents a 5- membered aromatic 
heterocyclyl group include thiazolyl and oxazolyl, especially oxazolyl. 
Suitable values for A.sup.1 when it represents a 6- membered aromatic 
heterocyclyl group include pyridyl or pyrimidinyl. 
Suitably R.sup.2 and R.sup.3 each represent hydrogen. 
Preferably, A.sup.1 represents a moiety of formula (a), (b) or (c): 
##STR3## 
wherein: R.sup.4 and R.sup.5 each independently represents a hydrogen 
atom, an alkyl group or a substituted or unsubstituted aryl group or when 
R.sup.4 and R.sup.5 are each attached to adjacent carbon atoms, then 
R.sup.4 and R.sup.5 together with the carbon atoms to which they are 
attached form a benzene ring wherein each carbon atom represented by 
R.sup.4 and R.sup.5 together may be substituted or unsubstituted; and in 
the moiety of formula (a) 
X represents oxygen or sulphur. 
Aptly, A.sup.1 represents a moiety of the abovedefined formula (a). 
Aptly, A.sup.1 represents a moiety of the abovedefined formula (b). 
Aptly. A.sup.1 represents a moiety of the abovedefined formula (c). 
In one favoured aspect R.sup.4 and R.sup.5 together represent a moiety of 
formula (d): 
##STR4## 
wherein R.sup.6 and R.sup.7 each independently represent hydrogen, 
halogen, substituted or unsubstituted alkyl or alkoxy. 
Suitably, R.sup.6 and R.sup.7 each independently represent hydrogen, 
halogen, alkyl or alkoxy. 
Favourably, R.sup.6 represents hydrogen. Favourably, R.sup.7 represents 
hydrogen. 
Preferably, R.sup.6 and R.sup.7 both represent hydrogen. 
In a further favoured aspect R.sup.4 and R.sup.5 each independently 
represent hydrogen, alkyl or a substituted or unsubstituted phenyl group 
and more favourably, R.sup.4 and R.sup.5 each independently represent 
hydrogen, alkyl or phenyl. 
Preferably, for the moiety of formula (a), R.sup.4 and R.sup.5 together 
represent the moiety of formula (d). 
Preferably, for the moieties of formula (b) or (c), R.sup.4 and R.sup.5 
both represent hydrogen. 
It will be appreciated that the five substituents of A.sup.2 include three 
optional substituents. Suitable optional substituents for the moiety 
A.sup.2 include halogen, substituted or unsubstituted alkyl or alkoxy. 
Favourably, A.sup.2 represents a moiety of formula (e): 
##STR5## 
wherein R.sup.8 and R.sup.9 each independently represent hydrogen, 
halogen, substituted or unsubstituted alkyl or alkoxy. 
Suitably, R.sup.8 and R.sup.9 each independently represent hydrogen, 
halogen, alkyl or alkoxy. Preferably, R.sup.8 and R.sup.9 each represent 
hydrogen. 
Favourably, X represents oxygen. Favourably, X represents sulphur. 
In one preferred aspect the present invention provides a class of 
compounds, which fall wholly within the scope of formula (I), of formula 
(II): 
##STR6## 
or a tautomeric form thereof, and/or a pharmaceutically acceptable salt 
thereof and/or a pharmaceutically acceptable solvate thereof, wherein 
A.sup.1, R.sup.1, R.sup.2, R.sup.3, and n are as defined in relation to 
formula (I) and R.sup.8 and R.sup.9 are as defined in relation to formula 
(e). 
Suitably, n represents an integer 2, 3 or 4, notably 2 or 3 and especially 
2. 
Suitably, R.sup.1 represents hydrogen, alkyl, acyl, especially acetyl, or 
benzyl. 
When R.sup.1 represents an alkyl group, examples of such alkyl groups 
include methyl and isopropyl. Preferably, R.sup.1 represents a methyl 
group. 
As indicated above a compound of formula (I) may exist in one of several 
tautomeric forms, all of which are encompassed by the present invention. 
It will be appreciated that the present invention encompasses all of the 
isomeric forms of the compounds of formula (I) and the pharmaceutically 
acceptable salts thereof, including any stereoisomeric forms thereof, 
whether as individual isomers or as mixtures of isomers. 
Suitable substituents for any heterocyclyl group include up to 4 
substituents selected from the group consisting of: alkyl, alkoxy, aryl 
and halogen or any two substituents on adjacent carbon atoms, together 
with the carbon atoms to which they are attached, may form an aryl group, 
preferably a benzene ring, and wherein the carbon atoms of the aryl group 
represented by the said two substituents may themselves be substituted or 
unsubstituted. 
When used herein the term `aryl` includes phenyl and naphthyl optionally 
substituted with up to five, preferably up to three, groups selected from 
halogen, alkyl, phenyl, alkoxy, haloalkyl, hydroxy, amino, nitro, carboxy, 
alkoxycarbonyl, alkoxycarbonylalkyl, alkylcarbonyloxy, or alkylcarbonyl 
groups. 
When used herein the term `halogen` refers to fluorine, chlorine, bromine 
and iodine; preferably chlorine. 
When used herein the terms `alkyl` and `alkoxy` relate to groups having 
straight or branched carbon chains,containing up to 12 carbon atoms. 
When used herein the term `acyl` includes alkylcarbonyl groups. Suitable 
alkyl groups are C.sub.1 -C.sub.12 alkyl groups, especially C.sub.1 
-C.sub.6 alkyl groups e.g. methyl, ethyl, n-propyl, iso-propyl, n-butyl, 
isobutyl or tert-butyl groups. 
Suitable substituents for any alkyl group include those indicated above in 
relation to the term "aryl". 
Suitable pharmaceutically acceptable salts include salts of the 
thiazolidinedione moiety, and, where appropriate, salts of carboxy groups. 
Suitable pharmaceutically acceptable salts of the thiazolidinedione moiety 
include metal salts especially alkali metal salts such as the lithium, 
sodium and potassium salts. 
Suitable pharmaceutically acceptable salts of carboxy groups include metal 
salts, such as for example aluminium, alkali metal salts such as sodium or 
potassium, alkaline earth metal salts such as calcium or magnesium and 
ammonium or substituted ammonium salts, for example those with lower 
alkylamines such as triethylamine, hydroxy alkylamines such as 
2-hydroxyethylamine, bis-(2-hydroxyethyl)-amine or 
tri-(2-hydroxyethyl)-amine, cycloalkylamines such as bicyclohexylamine, or 
with procaine, dibenzylpiperidine, N-benzyl-.beta.-phenethylamine, 
dehydroabietylamine, N,N'-bisdehydroabietylamine, glucamine, 
N-methylglucamine or bases of the pyridine type such as pyridine, 
collidine or quinoline. 
Suitable pharmaceutically acceptable solvates include hydrates. 
In a further aspect the present invention also provides a process for the 
preparation of a compound of formula (I), or a tautomeric form thereof, 
and/or a pharmaceutically acceptable salt thereof, and/or a 
pharmaceutically acceptable solvate thereof, which process comprises 
reacting a compound of formula (III): 
##STR7## 
wherein R.sup.2, R.sup.3 and A.sup.2 are as defined in relation to formula 
(I), and R.sup.a is a moiety convertible to a moiety of formula (f): 
##STR8## 
wherein R.sup.1 A.sup.1, and n are as defined in relation to formula (I), 
with an appropriate reagent capable of converting R.sup.a to the said 
moiety (f) and thereafter, if required, carrying out one or more of the 
following optional steps: 
(i) converting a compound of formula (I) to a further compound of formula 
(I); 
(ii) preparing a pharmaceutically acceptable salt of the compound of 
formula (I) and/or a pharmaceutically acceptable solvate thereof. 
Suitably, R.sup.a represents R.sup.1 HN-(CH.sub.2)n--O--wherein R.sup.1 and 
n are as defined in relation to formula (I). 
Suitably, when R.sup.a is R.sup.1 HN-(CH.sub.2)n--O--, an appropriate 
reagent capable of converting R.sup.a to a moiety (f) is a compound of 
formula (IV): 
EQU A.sup.1 -R.sup.x (IV) 
wherein A.sup.1 is as defined in relation to formula (I) and R.sup.x 
represents a leaving group. 
A suitable leaving group R.sup.x includes a halogen atom, preferably a 
chlorine or bromine atom, or a thioalkyl group for example a thiomethyl 
group. 
The reaction between the compound of formula (III) and the appropriate 
reagent may be carried out under conditions suitable to the particular 
compound of formula (III) and the reagent chosen; thus for example the 
abovementioned reaction between a compound of formula (III) wherein 
R.sup.a represents R.sup.1 HN-(CH.sub.2)n--O-- and the compound of formula 
(IV), may be carried out in any suitable solvent, for example 
tetrahydrofuran, at a temperature in the range of between 0.degree. and 
60.degree. C. 
A compound of formula (III) may be prepared from a compound of formula (V): 
##STR9## 
wherein A.sup.2 is as defined in relation to the compound of formula (I) 
and R.sup.b is a moiety R.sup.a, or a moiety convertible to a moiety 
R.sup.a ; by reaction of the compound of formula (V) with 
2,4-thiazolidinedione; and thereafter if required carrying out one or more 
of the following optional steps: 
(i) reducing a compound of formula (III) wherein R.sup.2 and R.sup.3 
together represent a bond, into a compound of formula (III) wherein 
R.sup.2 and R.sup.3 each represent hydrogen; 
(ii) converting a moiety R.sup.b to a moiety R.sup.a. 
The reaction between the compound of formula (V) and 2,4-thiazolidinedione 
will of course be carried out under conditions suitable to the nature of 
the compound of formula (V), in general the reaction being carried out in 
a solvent such as toluene, suitably at an elevated temperature such as the 
reflux temperature of the solvent and preferably in the presence of a 
suitable catalyst such as piperidinium acetate or benzoate. Favourably, in 
the reaction between the compound of formula (V) and 
2,4-thiazolidinedione, the water produced in the reaction is removed from 
the reaction mixture, for example by means of a Dean and Stark apparatus. 
When R.sup.a represents R.sup.1 HN-(CH.sub.2)n--O--, a suitable value for 
R.sup.b is a hydroxyl group. 
The moiety R.sup.b may be converted to the moiety R.sup.a by any suitable 
means, for example when R.sup.b represents a hydroxyl group and R.sup.a 
represents RIHN(CH.sub.2)n--O-- the appropriate conversion may be carried 
out by coupling a compound of formula (VA): 
##STR10## 
wherein R.sup.2, R.sup.3 and A.sup.2 are as defined in relation to formula 
(I) and R.sup.z is hydrogen or a nitrogen protecting group, with a 
compound of formula (VI): 
EQU R.sup.1 NR.sup.x (CH.sub.2).sub.n --OH (VI) 
wherein R.sup.1 and n are as defined in relation to formula (I) and R.sup.x 
is hydrogen or a nitrogen protecting group, in the presence of a suitable 
coupling agent; and thereafter, if required, carrying out one or more of 
the following optional steps: 
(i) reducing a compound of formula (III) wherein R.sup.2 and R.sup.3 
together represent a bond, to a compound of formula (III) wherein R.sup.2 
and R.sup.3 each represent hydrogen; 
(ii) removing any nitrogen protecting group. 
A suitable coupling agent for the coupling reaction between the compound of 
formula (VA) and (VI) is provided by diethylazodicarboxylate and 
triphenylphosphine. The coupling reaction may be carried out in any 
suitable solvent at a low to medium temperature, for example in 
tetrahydrofuran at a temperature in the range of between 0.degree. and 
60.degree. C. 
One example of the preparation of a compound of formula (VA) is that 
wherein a compound falling within formula 
(v) of particular formula (VII): 
##STR11## 
wherein A.sup.2 is as defined in relation to formula (I), and R.sup.11 
represents a hydroxyl group or a protected hydroxyl group, is reacted with 
2,4-thiazolidinedione; and thereafter if required removing any protecting 
group. 
Preferably, R.sup.11 represents a benzyloxy group. 
Suitable conditions for the reaction between a compound of formula (VII) 
and 2,4-thiazolidinedione are those defined above in relation to the 
reaction between the compounds of formula (V) and 2,4-thiazolidinedione. 
The compounds of formula (IV), (VI) and (VII) are either known compounds or 
are prepared using methods analogous to those used to prepare known 
compounds. 
Suitable protecting groups in any of the abovementioned reactions are those 
used conventionally in the art. Thus, for example, a suitable nitrogen 
protecting group is a benzyl group or a benzyloxycarbonyl group and a 
suitable hydroxyl protecting group is a benzyl group. 
The methods of formation and removal of such protecting groups are those 
conventional methods appropriate to the molecule being protected. Thus for 
example when R.sup.11 represents a benzyloxy group such group may be 
prepared by treatment of the appropriate compound of formula (VII), 
wherein R.sup.11 is a hydroxyl group with a benzyl halide, such as benzyl 
bromide, and thereafter when required the benzyl group may be conveniently 
removed using a mild ether cleavage reagent such as trimethylsilyliodide. 
A compound of formula (I), or a tautomeric form thereof, and/or a 
pharmaceutically acceptable salt thereof and/or a pharmaceutically 
acceptable solvate thereof, may also be prepared by reacting a compound of 
formula (VIII): 
##STR12## 
wherein R.sup.1 A.sup.1 A.sup.2, and n are as defined in relation to 
formula (I) with 2,4-thiazolidinedione; and thereafter if required 
carrying out one or more of the following optional steps: 
(i) converting a compound of formula (I) into a further compound of formula 
(I); 
(ii) preparing a pharmaceutically acceptable salt of a compound of formula 
(I) and/or a pharmaceutically acceptable solvate thereof. 
The reaction between a compound of formula (VIII) and 2,4-thiazolidinedione 
may suitably be carried out under analogous conditions to those used in 
the reaction between a compound of formula (V) and 2,4-thiazolidinedione. 
A compound of formula (VIII) may be prepared by reacting a compound of 
formula (IX): 
##STR13## 
wherein A.sup.2 is as defined in relation to formula (I) and R.sup.a is as 
defined in relation to formula (III), with an appropriate reagent capable 
of converting R.sup.a to the above defined moiety (f). 
Suitable values for R.sup.a include those described above in relation to 
the compound of formula (III). Thus R.sup.a may represent R.sup.1 
HN-(CH.sub.2)n--O--, as defined above, and hence the appropriate compound 
of formula (IX) may be reacted with a reagent of the abovedefined formula 
(IV) to provide the required compound of formula (VIII). 
Suitable reaction conditions for the reaction of the compound of formula 
(IX) and the appropriate reagent may include those described above in 
relation to the preparation of compound (III) with the said appropriate 
reagent. 
Preferably, for the compound of formula (IX), R.sup.a represents a leaving 
group, especially a fluorine atom. When R.sup.a represents a leaving 
group, preferably a fluorine atom, a particularly appropriate reagent is a 
compound of formula (X): 
##STR14## 
wherein R.sup.1 A.sup.1, and n are as defined in relation to formula (I). 
The reaction between the compounds of formulae (IX) and (X) may be carried 
out under any suitable conditions, for example in a solvent such as 
dimethylformamide or dimethylsulphoxide at an elevated temperature for 
example in the range of between 100.degree. to 150.degree. C., suitably in 
the presence of a base such as sodium hydride or potassium carbonate. 
In the compound of formula (IX) R.sup.a may also represent a hydroxyl 
group. 
When R.sup.a, in the compound of formula (IX), represents a hydroxyl group 
a particularly appropriate reagent is a compound of the above defined 
formula (X) or a compound of formula (XA): 
##STR15## 
wherein A.sup.1 R.sup.1 and n are as defined in relation to formula (X) 
and R.sup.y represents a tosylate or mesylate group. 
The reaction between the compound of formula (IX) wherein R.sup.a is a 
hydroxyl group and the reagent of the abovedefined formula (X) may 
suitably be carried out in an aprotic solvent, such as tetrahydrofuran, at 
low to medium temperature, for example at ambient temperature, and 
preferably in the presence of a coupling agent such as that provided by 
triphenylphosphine and diethylazodicarboxylate. 
The reaction between the compound of formula (IX), wherein R.sup.a is a 
hydroxyl group, and the reagent of the abovedefined formula (XA) may be 
carried out in an aprotic solvent, such as dimethylformamide, at a low to 
elevated temperature, for example in the range of from 50.degree. C. to 
120.degree. C. and preferably in the presence of a base, such as sodium 
hydride. 
The compound of formula (XA) may be prepared from the corresponding 
compound of formula (X) by reaction with either a tosyl halide or a mesyl 
halide in a solvent such as pyridine. 
The compounds of formula (IX) are known compounds or compounds prepared by 
methods analogous to those used to prepare known compounds, for example 
4-fluorobenzaldehyde and 4-hydroxybenzaldehyde are known commercially 
available compounds. 
The reagent of formula (X) may be prepared by reacting a compound of the 
hereinabove defined formula (IV), with a compound of the hereinbefore 
defined formula (VI) and thereafter if required removing any nitrogen 
protecting group using the appropriate conventional conditions. 
The reaction between the compounds of formula (IV) and (VI) may be carried 
out under any suitable conditions, such as in solvent, for example in an 
aprotic solvent such as tetrahydrofuran, at a low to medium temperature, 
for example a temperature in the range of from 0.degree. to 60.degree. C. 
Favourably when R.sup.1 represents hydrogen the reaction is carried out 
using the compound of formula (VI) as a solvent at a low to elevated 
temperature, suitably an elevated temperature such as in the range of 
between 100.degree. and 170.degree. C. 
The abovementioned conversion of a compound of formula (I) into a further 
compound of formula (I) includes the following conversions: 
(a) reducing a compound of formula (I) wherein R.sup.2 and R.sup.3 together 
represent a bond, to a compound of formula (I) wherein R.sup.2 and R.sup.3 
each represent hydrogen; and 
(b) converting one group R.sup.1 into another group R.sup.1. 
The conversion of a compound of formula (I) to a further compound of 
formula (I) may be carried out by using any appropriate conventional 
procedure. 
A suitable reduction method for the abovementioned conversion (a) includes 
catalytic reduction or the use of a metal/solvent reducing system. 
Suitable catalysts for use in the catalytic reduction are palladium on 
carbon catalysts, preferably a 10% palladium on charcoal catalyst; the 
reduction being carried out in a solvent, for example dioxan, suitably at 
ambient temperature. 
Suitable metal/solvent reducing systems include magnesium in methanol. 
The abovementioned reduction of a compound of formula (III) wherein R.sup.2 
and R.sup.3 together represent a bond to a compound of formula (III) 
wherein R.sup.2 and R.sup.3 each represent hydrogen, may be carried out 
under analogous conditions to those referred to above in conversion (a) of 
the compound of formula (I). 
In the abovementioned conversion (b), suitable conversions of one group 
R.sup.1 into another group R.sup.1 includes converting a group R.sup.1 
which represents hydrogen into a group R.sup.1 which represents an acyl 
group. 
The conversion of a compound of formula (I) wherein R.sup.1 represents 
hydrogen into a compound of formula (I) wherein R.sup.1 represents acyl 
may be carried out using any appropriate conventional acylation procedure, 
such as by treating an appropriately protected compound of formula (I) 
with an acylating agent. For example acetic anhydride may be used to 
prepare the compound of formula (I) wherein R.sup.1 is acetyl. 
It will be appreciated that in the abovementioned conversions (a) and (b), 
any reactive group in the compound of formula (I) would be protected, 
according to conventional chemical practice, where necessary. 
Where appropriate the isomeric forms of the compounds of formula (I) and 
the pharmaceutically acceptable salts thereof may be prepared as 
individual isomers using conventional chemical procedures. 
As mentioned above the compounds of the invention are indicated as having 
useful therapeutic properties: 
The present invention accordingly provides a compound of formula (I), or a 
tautomeric form thereof and/or a pharmaceutically acceptable salt thereof 
and/or a pharmaceutically acceptable solvate thereof, for use as an active 
therapeutic substance. 
Thus the present invention provides a compound of formula (I), or a 
tautomeric form thereof and/or a pharmaceutically acceptable salt thereof 
and/or a pharmaceutically acceptable solvate thereof, for use in the 
treatment of and/or prophylaxis of hyperglycaemia. 
In a further aspect the present invention also provides a compound of 
formula (I), or a tautomeric form thereof and/or a pharmaceutically 
acceptable salt thereof and/or a pharmaceutically acceptable solvate 
thereof, for use in the treatment and/or prophylaxis of hyperlipidaemia. 
As indicated hereinbefore the present invention also provides a compound of 
formula (I) or a tautomeric form thereof and/or a pharmaceutically 
acceptable salt thereof and/or a pharmaceutically acceptable solvate 
thereof for use in the treatment of hypertension, cardiovascular disease 
and certain eating disorders. 
A compound of formula (I), or a tautomeric form thereof and/or a 
pharmaceutically acceptable salt thereof and/or a pharmaceutically 
acceptable solvate thereof, may be administered per se or, preferably, as 
a pharmaceutical composition also comprising a pharmaceutically acceptable 
carrier. 
Accordingly, the present invention also provides a pharmaceutical 
composition comprising a compound of the general formula (I), or a 
tautomeric form thereof, or a pharmaceutically acceptable salt thereof, or 
a pharmaceutically acceptable solvate thereof, and a pharmaceutically 
acceptable carrier therefor. 
As used herein the term `pharmaceutically acceptable` embraces compounds, 
compositions and ingredients for both human and veterinary use: for 
example the term `pharmaceutically acceptable salt` embraces a 
veterinarily acceptable salt. 
The composition may, if desired, be in the form of a pack accompanied by 
written or printed instructions for use. 
Usually the pharmaceutical compositions of the present invention will be 
adapted for oral administration, although compositions for administration 
by other routes, such as by injection and percutaneous absorption are also 
envisaged. 
Particularly suitable compositions for oral administration are unit dosage 
forms such as tablets and capsules. Other fixed unit dosage forms, such as 
powders presented in sachets, may also be used. 
In accordance with conventional pharmaceutical practice the carrier may 
comprise a diluent, filler, disintegrant, wetting agent, lubricant, 
colourant, flavourant or other conventional adjuvant. 
Typical carriers include, for example, microcrystalline cellulose, starch, 
sodium starch glycollate, polyvinylpyrrolidone, polyvinylpolypyrrolidone, 
magnesium stearate, sodium lauryl sulphate or sucrose. 
Most suitably the composition will be formulated in unit dose form. Such 
unit dose will normally contain an amount of the active ingredient in the 
range of from 0.1 to 1000 mg, more usually 0.1 to 500 mg, and more 
especially 0.1 to 250 mg. 
The present invention further provides a method for the treatment and/or 
prophylaxis of hyperglycaemia in a human or non-human mammal which 
comprises administering an effective, non-toxic, amount of a compound of 
the general formula (I), or a tautomeric form thereof and/or a 
pharmaceutically acceptable salt thereof and/or a pharmaceutically 
acceptable solvate thereof to a hyperglycaemic human or non-human mammal 
in need thereof. 
The present invention further provides a method for the treatment of 
hyperlipidaemia in a human or non-human mammal, which comprises 
administering an effective, non-toxic, amount of a compound of formula 
(I), or a tautomeric form thereof and/or a pharmaceutically acceptable 
salt thereof and/or a pharmaceutically acceptable solvate thereof, to a 
hyperlipidaemic human or non-human mammal in need thereof. 
Conveniently, the active ingredient may be administered as a pharmaceutical 
composition hereinbefore defined, and this forms a particular aspect of 
the present invention. 
In the treatment and/or prophylaxis of hyperglycaemic humans, and/or the 
treatment and/or prophylaxis of hyperlipidaemic human, the compound of the 
general formula (I), or a tautomeric form thereof and/or a 
pharmaceutically acceptable salt thereof and/or a pharmaceutically 
acceptable solvate thereof, may be taken in doses, such as those described 
above, one to six times a day in a manner such that the total daily dose 
for a 70 kg adult will generally be in the range of from 0.1 to 6000 mg, 
and more usually about 1 to 1500 mg. 
In the treatment and/or prophylaxis of hyperglycaemic non-human mammals, 
especially dogs, the active ingredient may be adminstered by mouth, 
usually once or twice a day and in an amount in the range of from about 
0.025 mg/kg to 25 mg/kg, for example 0.1 mg/kg to 20 mg/kg. Similar dosage 
regimens are suitable for the treatment and/or prophylaxis of 
hyperlipidaemia in non-human mammals. 
The dosages regimens for the treatment of hypertension, cardiovascular 
disease and eating disorders will generally be those mentioned above in 
relation to hyperglycaemia. 
In a further aspect the present invention provides the use of a compound of 
formula (I), or a tautomeric form thereof and/or a pharmaceutically 
acceptable salt thereof and/or a pharmaceutically acceptable solvate 
thereof, for the manufacture of a medicament for the treatment and/or 
prophylaxis of hyperglycaemia. 
The present invention also provides the use of a compound of formula (I), 
or a tautomeric form thereof and/or a pharmaceutically acceptable salt 
thereof, and/or a pharmaceutically acceptable solvate thereof, for the 
manufacture of a medicament for the treatment and/or prophylaxis of 
hyperlipidaemia, hypertension, cardiovascular disease or certain eating 
disorders.