Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1993-04-30
1995-12-26
Ivy, C. Warren
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
548183, 546209, 514326, C07D27734, A61K 31425
Patent
active
054788510
DESCRIPTION:
BRIEF SUMMARY
This application is the U.S. National stage of PCT/GB91/10833 filed Oct. 18, 1991.
This invention relates to certain novel compounds, 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 amide-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): ##STR1## or a tautomeric form thereof and/or a pharmaceutically acceptable salt thereof, and/or a pharmaceutically acceptable solvate thereof, wherein:
A.sup.1 represents an alkyl group, a substituted or unsubstituted aryl group, an aralkyl group wherein the alkylene or the aryl moiety may be substituted or unsubstituted or a substituted or unsubstituted aromatic heterocyclyl group;
A.sup.2 represents a benzene ring having in total up to three optional substituents;
R.sup.1 represents a hydrogen atom, an alkyl group, an aralkyl group wherein the alkyl or the aryl moiety may be substituted or unsubstituted, or a substituted or unsubstituted aryl group;
or A.sup.1 together with R.sup.1 represents substituted or unsubstituted C.sub.3-4 polymethylene group, optional substituents for the polymethylene group being selected from alkyl or aryl or adjacent substituents together with the methylene carbon atoms to which they are attached form a substituted or unsubstituted phenylene group;
R.sup.2 and R.sup.3 each represent hydrogen, or R.sup.2 and R.sup.3 together represent a bond;
X represents O or S; and
n represents an integer in the range of from 2 to 6.
When A.sup.1 represents an aryl group, the aryl group is suitably an unsubstituted aryl group, for example a phenyl group.
When A .sup.1 represents an aralkyl group, the aralkyl group is suitably a group of formula aryl(CH.sub.2).sub.m, wherein m is 1, 2, 3 or 4, preferably 1 or 2, for example a benzyl group.
When A.sup.1 represents an aryl group or an aralkyl group, favoured substituents for the aryl group or the aryl moiety of the aralkyl group are halogen and alkoxy, for example chlorine and methoxy.
Particular examples of A.sup.1 include phenyl, benzyl and 2-phenylethyl.
Favourably, A.sup.1 together with R.sup.1 represents substituted or unsubstituted C.sub.3-4 polymethylene group, optional substituents for the polymethylene group being selected from alkyl or aryl or adjacent substituents together with the methylene carbon atoms to which they are attached form a substituted or unsubstituted phenylene group.
Favoured substituted or unsubstituted C.sub.3-4 -polymethylene groups include substituted or unsubstituted propylene groups.
Favoured optional substituents for the C.sub.3-4 -polymethylene group, include C.sub.1-6 -alkyl and phenyl groups or adjacent substituents together with the methylene carbon atoms to which they are attached form an optionally substituted phenylene group.
Preferred optional substituents for the C.sub.3-4 polymethylene group are adjacent substituents which together with the methylene carbon atoms to which they are attached form an optionally substituted phenylene group.
In a particularly favoured aspect, the moiety A.sup.1 --CO--NR.sup.1 -- represents a 2,3-dihydro-1H-isoindol-1-on-2-yl group or a 3,4-dihydr
REFERENCES:
patent: 4572912 (1985-05-01), Yoshioka et al.
patent: 4918091 (1990-04-01), Cantello
patent: 5104888 (1992-04-01), Yoshioka et al.
patent: 5132317 (1992-07-01), Cantello
patent: 5330998 (1994-07-01), Clark
Sohda, Takashi, Chem Pharm. Bull, 30(10), pp. 3580-3600, 1982.
Chem. Pharm. Bull., vol. 30, No. 10, 1982, T. Sohda et al.: "Studies on antidiabetic agents. II Synthesis of 5-(4-(1-methylcyclohexylmethoxy)-benzyl)thiazolidine-2,4-dione(ADD-3878) and its derivatives", see p. 3580-p.3600 see p. 3589, lines 10-12; p. 3587, Table V, compounds Nos. 76-80, 82. 1982.
Cantello Barrie C. C.
Haigh David
Hindley Richard M.
Beecham Group plc
Ivy C. Warren
Kinzig Charles M.
Lentz Edward T.
M. Mach D. Margaret
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