Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1995-08-25
1998-03-17
Daus, Donald G.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514252, 514256, 514259, 514314, 514340, 544238, 544284, 544333, 546167, 5462741, 548236, A61K 3142, C07D41302
Patent
active
057287201
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to novel isoxazolidinedione derivatives. Note particularly, the present invention relates to novel isoxazolidinedione derivatives which have hypoglycemic action and hypolipidemic action, and are useful as therapeutic agents for diabetes and the complications thereof, and as therapeutic agents for the related diseases such as hyperlipidemia.
2. Description of the Related Art
In general, the treatment of non-insulin-dependent diabetes mellitus (NIDDM) involves a combination of alimentotherapy, kinesitherapy, and administration of insulin or oral hypoglycemic agents. As the oral hypoglycemic agents, there are currently known sulfonylureas such as tolbutamide, chlorpropamide, acetohexamide, glibenclamide and tolazamide and biguanides such as phenformin, buformin and metformin.
While the sulfonylureas have strong hypoglycemic action, they sometimes induce severe and prolonged hypoglycemia, and chronic use thereof may impair their effectiveness. In addition, the biguanides frequently induce severe lactic acidosis. For these reasons, the use of these medications has required considerable attention.
Japanese Patent Unexamined Publication No. 85372/1986 corresponding to U.S. Pat. No. 4,725,610 teaches that thiazolidinedione derivatives such as e! have hypoglycemic action, and Japanese Patent Unexamined Publication No. 51189/1985 corresponding to U.S. Pat. No. 4,572,912 teaches that thiazolidinedione derivatives such as 4-thiazolidinedione! have hypoglycemic action. It has been also taught that oxazolidinedione derivatives such as ! described in Japanese Patent Unexamined Publication No. 170478/1991 corresponding to U.S. Pat. No. 5,498,621 and ione! described in WO92/02520 CORRESPONDING to U.S. Pat. No. 5,391,565 possess hypoglycemic action and cholesterol lowering action.
However, these compounds are not necessarily satisfactory in terms of activity, and the use thereof rather causes anxiety when their side effects (e.g. toxicity) are taken into consideration. These publications do not include a description suggesting an isoxazolidinedione derivative such as the compounds of the present invention.
SUMMARY OF THE INVENTION
The present inventors have conducted intensive studies in an effort to provide a compound effective as a therapeutic drug for diabetes, the complications thereof and hyperlipidemia, and found novel low toxic isoxazolidinedione derivatives having superior hypoglycemic action and hypolipidemic action, which resulted in the completion of the invention.
Accordingly, the present invention relates to novel isoxazolidinedione derivatives of the following (1) to (14).
(1) Novel isoxazolidinedione derivatives of the formula (I) ##STR3## wherein R is an optionally substituted aromatic hydrocarbon, an optionally substituted allcyclic hydrocarbon, an optionally substituted heterocyclic group, an optionally substituted condensed heterocyclic group or a group of the formula ##STR4## wherein R.sub.1 is an optionally substituted aromatic hydrocarbon, an optionally substituted alicyclic hydrocarbon, an optionally substituted heterocyclic group or an optionally substituted condensed heterocyclic group, R.sub.2 and R.sub.3 are the same or different and each is a hydrogen atom or a lower alkyl, and X is an oxygen atom, a sulfur atom or a secondary amino; pharmaceutically acceptable salts thereof.
(2) The novel isoxazolidinedione derivatives of the above (1) wherein R.sub.4 is a hydrogen atom and R.sub.5 is a lower alkyl, and pharmaceutically acceptable salts thereof.
(3) The novel isoxazolidinedione derivatives of the above (2) wherein R is an optionally substituted phenyl, an optionally substituted 5- or 6-membered aromatic heterocyclic group having 1 or 2 hetero atoms selected from sulfur atom, oxygen atom and nitrogen atom, or an optionally substituted condensed aromatic heterocyclic group wherein such aromatic heterocyclic ring and a benzene ring are condensed, and pharmaceutically acceptable salts thereof.
(4) The novel isoxa
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Burger, Ed. "Medicinal Chemistry 2nd Ed" Interscience, N.Y. 1960 p. 42.
Derwent Abstract of Japanese Patent Unexamined Publication JP-A-61-85372.
Derwent Abstract of Japanese Patent Unexamined Publication JP-A-60-51189.
Derwent Abstract of Japanese Patent Unexamined Publication JP-3-170478.
Derwent Abstract of WO92/02520.
Daus Donald G.
Japan Tobacco Inc.
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