Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1985-03-07
1986-04-15
Fan, Jane T.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
546280, A61K 3144, C07D27724
Patent
active
045828393
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to novel thiazolidinedione derivatives having blood sugar- and lipid-lowering activity, to a process for producing the same, and to pharmaceutical compositions containing the same.
BACKGROUND ART
A great variety of biguanide and sulfonylurea compounds have been conventionally employed as a therapeutic agent for diabetes. However, biguanide compounds cause lactic acidosis and therefore, are hardly used at present, while sulfonylurea compounds exhibit potent blood sugar lowering activity but often bring about serious hypoglycemia, thus requiring the precautions for use. The present inventors, after extensive research to find a compound having blood sugar lowering activity which is free from such drawbacks, discovered certain novel thiazolidinedione derivatives having excellent blood sugar- and lipid-lowering activity.
DISCLOSURE OF THE INVENTION
The present invention relates to:
1. Thiazolidinedione derivatives of the general formula: ##STR2## wherein R.sup.1 and R.sup.2 are the same or different and each represent hydrogen or a lower alkyl group; R.sup.3 is hydrogen or acyl group; n is 0 or 1,
2. A process for producing thiazolidinedione derivatives of the general formula (I), characterized in that said process comprises reacting a compound of the general formula: ##STR3## wherein R.sup.1, R.sup.2 and n are as defined hereinbefore; R.sup.4 is hydrogen or an acyl group; R.sup.5 is hydrogen or a lower alkyl group; X is a halogen atom with thiourea to produce a compound of the general formula: ##STR4## wherein each of the symbols is as defined hereinbefore and hydrolyzing the resulting compound, followed by acylating if necessary, and
3. Pharmaceutical compositions which contain thiazolidinedione derivatives of the general formula (I) or salts thereof.
With reference to the above general formulae (I), (II) and (III), examples of the lower alkyl group represented by R.sup.1 and R.sup.2 include lower alkyl groups having 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl and butyl, preferably those having 1 to 3 carbon atoms in particular, and these may be substituted for hydrogen atoms at arbitrary positions of the pyridine ring. As the acyl group represented by R.sup.3, by way of example, there may be mentioned formyl, alkylcarbonyl having 2 to 6 carbon atoms (e.g. acetyl, propionyl, butyryl, isobutyryl, pentanoyl, isopentanoyl, hexanoyl, etc.), aralkylcarbonyl having 8 to 9 carbon atoms (e.g. phenylacetyl, phenylpropionyl, etc.), arylcarbonyl having 1 to 8 carbon atoms (e.g. benzoyl, p-toluoyl, etc.). As the acyl group represented by R.sup.4, there may be mentioned the same acyl groups represented by R.sup.3. As the lower alkyl group represented by R.sup.5, there may be mentioned the above-described lower alkyl groups represented by R.sup.1 and R.sup.2. Examples of the halogen atom represented by X include chlorine, bromine and iodine.
The thiazolidinedione derivatives of the general formula (I) are amphoteric compounds having acid nitrogen in the thiazolidine ring and alkaline nitrogen in the pyridine ring, and exist both in acid and base salts. Referring to salts of the thiazolidinedione derivatives (I), examples of the acid salts include inorganic acid salts, such as hydrochlorides, hydrobromides, sulfates, phosphates and methanesulfonates, and organic acid salts, such as toluenesulfonates, oxalates, malonates, maleates, fumarates, succinates, tartrates and malates, while examples of the base salts include metal salts, such as sodium salts, potassium salts, aluminum salts, magnesium salts and calcium salts.
As specific examples of the thiazolidinedione derivatives of the general formula (I) and their salts, there may be mentioned the following compounds: one, one e, ione, e, e, ione, ne, ne, one, and one.
The reaction of a compound of the general formula (II) with thiourea is normally conducted in a solvent, such as alcohols (e.g., methanol, ethanol, propanol, 2-propanol, butanol, isobutanol, 2-methoxyethanol, etc.), dimethylsulfoxide and sulfo
REFERENCES:
patent: 4287200 (1981-09-01), Kawamatsu et al.
patent: 4340605 (1982-07-01), Kawamatsu
Sohda et al, "Studies on Anti Diabetic Agents", Chem. Pharm. Bull., Chem. Abs. 98:160624h.
Kawamatsu et al, "Thiazolidine Derivatives", Chem. Abs. 93:114506v.
Fujita Takeshi
Meguro Kanji
Fan Jane T.
Takeda Chemical Industries Ltd.
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