N-substituted dioxothiazolidylbenzamide derivatives and process for producing the same

• US 5,948,803 A
• Filed: 06/16/1998
• Issued: 09/07/1999
• Est. Priority Date: 12/18/1995
• Status: Expired due to Fees

• Current Assignee: Kyorin Pharmaceutical Company Limited (Kyorin Holdings Incorporated)
• Original Assignee: Kyorin Pharmaceutical Company Limited (Kyorin Holdings Incorporated)
• Inventors: Maeda, Toshio, Kinoshita, Susumu, Awano, Katsuya, Tsunoda, Masaki, Satoh, Hiroya, Murakami, Koji, Nomura, Masahiro
• Primary Examiner(s): Morris, Patricia L.
• Application Number:
  US09/077,899
• Time in Patent Office: 448 Days
• Field of Search: 548/183, 514/369
• US Class Current: 514/369
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 277/34 Oxygen atoms
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links

Abstract

The invention provides novel N-substituted dioxothiazolidylbenzamide derivatives that improve the insulin resistance and have potent hypoglycemic effect and lipid-lowering effect, and the process for preparing them, and relates to N-substituted dioxothiazolidylbenzamide derivatives characterized by being represented by a general formula (1) ##STR1## wherein R¹ and R² denote identically or differently hydrogen atoms, lower alkyl groups with carbon atoms of 1 to 4, lower alkoxy groups with carbon atoms of 1 to 3, lower haloalkyl groups with carbon atoms of 1 to 3, lower haloalkoxy groups with carbon atoms of 1 to 3, halogen atoms or hydroxyl groups, or R¹ and R² combine to form a methylenedioxy group, R³ denotes a hydrogen atom, lower alkoxys group with carbon atoms of 1 to 3, hydroxyl group or halogen atom, R⁴ denotes a hydrogen or lower alkyl group with carbon atoms of 1 to 3, n denotes an integer of 0 to 2, and X denotes N or CH!, and process for preparing the same.

Claims

1. An N-substituted dioxothiazolidylbenzamide compound having the formula (I):

##STR15## wherein R¹ and R² are each independently hydrogen, C₁ -C₄ lower alkyl, C₁ -C₃ lower alkoxy, C₁ -C₃ haloalkyl, C₁ -C₃ haloalkoxy, halogen or hydroxyl;

or R¹ or R² together form methylenedioxy;

R³ is hydrogen, C₁ -C₃ lower alkoxy, hydroxy or halogen;

R⁴ is hydrogen or C₁ -C₃ alkyl;

n is an integer of 0 to 2; and

X is CH;

or a pharmaceutically acceptable salt thereof.

2. The N-substituted dioxothiazolidylbenzamide compound of claim 1, wherein R¹ and R² are each independently 3-CF₃, H, 4-t-bu, 4-CF₃ O, or 4-CF₃ or together form 3,4-methylenedioxy.

3. The N-substituted dioxothiazolidylbenzamide compound of claim 1, wherein R⁴ is H or CH₃.

4. The N-substituted dioxothiazolidylbenzamide compound of claim 1, wherein n is 1.

5. The N-substituted dioxothiazolidylbenzamide compound of claim 1, which is N-(4-trifluromethylbenzyl)-5-(2,4,-dioxothiazolidine-5-yl)-2-methoxybenzamide, or a pharmaceutically acceptable salt thereof.

6. The N-substituted dioxothiazolidylbenzamide compound of claim 1, which is N-(3-trifluoromethylbenzyl)-5-(2,4-dioxothiazolidin-5-yl)-2-methoxybenzamide, or a pharmaceutically acceptable salt thereof.

7. The N-substituted dioxothiazolidylbenzamide compound of claim 1, wherein said pharmaceutically acceptable salt is selected from the group consisting of alkali metal salts, alkaline earth metal salts and aluminum salt.

8. The N-substituted dioxothiazolidylbenzamide compound of claim 4, wherein said alkali metal salts are selected from the group consisting of sodium and potassium salts.

9. The N-substituted dioxothiazolidylbenzamide compound of claim 7, wherein said alkaline metal salts are selected from the group consisting of calcium and magnesium salts.

10. The N-substituted dioxothiazolidyl benzamide compound of claim 1, which is an optical isomer mixture.

11. The N-substituted dioxothiazolidyl benzamide compound of claim 10, which is an optical isomer.

12. A hypoglycemic composition, comprising:

a) one or more of the N-substituted dioxothiazolidylbenzamide compounds of claim 1; and

b) a pharmaceutically acceptable carrier.