Treating complications of diabetes mellitus with hydantoin derivatives

• US 4,540,704 A
• Filed: 06/07/1983
• Issued: 09/10/1985
• Est. Priority Date: 07/21/1980
• Status: Expired due to Fees

• Current Assignee: Eisai Company Limited (Eisai Medical Research Incorporated)
• Original Assignee: Eisai Company Limited (Eisai Medical Research Incorporated)
• Inventors: Tanaka, Satoru, Sato, Tadashi, Ueda, Kouichiro, Wakabayashi, Tsuneo, Ohtsuka, Issei, Kunii, Toshinobu, Ohgoh, Toshiharu, Kawase, Mayumi, Kagei, Kengo, Hideki, Ono
• Primary Examiner(s): Schwartz, Richard A.
• Application Number:
  US06/500,801
• Time in Patent Office: 826 Days
• Field of Search: 548/309, 424/273 R
• US Class Current: 514/389
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/12 for cataracts
• 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 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 493/10 Spiro-condensed systems
• CPC Class Codes: C07D 495/10 Spiro-condensed systems

Abstract

Novel hydantoin derivatives and salts thereof, the process for the preparation thereof, and medicines containing the same, wherein the hydantoin derivatives are represented by the general formula: ##STR1## wherein X₁ and X₂, which may be the same or different, independently represent a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group; Y represents an oxygen atom or sulfur atom, R₁ and R₂, which may be the same or different, independently represent a hydrogen atom, a lower alkyl group or phenyl group, or both may form a ring with carbon atoms, excluding the case wherein both R₁ and R₂ are hydrogen atom, and n represents 0 or 1. The novel hydantoin derivatives and salts thereof have excellent effects for the treatment of the complications of diabetes mellitus.

Claims

1. A hydantoin derivative represented by the formula:

##STR16## wherein X₁ and X₂, which may be the same or different, independently represent a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group, Y represents an oxygen atom or sulfur atom, R₁ represents hydrogen and R₂ represents a lower alkyl group, and n represents 0 or 1, or a pharmaceutically acceptable salt thereof.

2. The hydantoin derivative or salt thereof according to claim 1 wherein said hydantoin derivative is represented by the formula:

##STR17## wherein X₁ and X₂, which may be the same or different, independently represent a hydrogen atom, a halogen atom, a lower alkyl group, or a lower alkoxy group, R₁ represents hydrogen and R₂ represents a lower alkyl group, and n represents 0 or 1.

3. The hydantoin derivative or salt thereof according to claim 1, whrein said hydantoin derivative is represented by the formula:

##STR18## wherein X₁ and X₂, which may be the same or different, independently represent a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group, R₁ represents hydrogen and R₂ represents a lower alkyl group.

4. The hydantoin derivative or salt thereof according to claim 1, wherein said hydantoin derivative is 6-fluoro-2-methyl-spiro-[chroman-4,4'"'"'-imidazolidine]-2'"'"',5'"'"'-dione.

5. The hydantoin derivative or salt thereof according to claim 1, wherein said hydantoin derivative is 6-chloro-2-methyl-spiro-[chroman-4,4'"'"'-imidazolidine]-2'"'"',5'"'"'-dione.

6. The hydantoin derivative or salt thereof according to claim 1, wherein said hydantoin derivative is 5-chloro-2-methyl-spiro-[benzofuran-3,4'"'"'-imidazolidine]-2'"'"',5'"'"'-dione.

7. The hydantoin derivative or salt thereof according to claim 1, wherein said hydantoin derivative is 6,7-dichloro-2-methyl-spiro-[chroman-4,4'"'"'-imidazolidine]-2,'"'"',5'"'"'-dione.

8. The hydantoin derivative or salt thereof according to claim 1, wherein said hydantoin derivative is 7-chloro-2-methyl-spiro-[chroman-4,4'"'"'-imidazolidine]-2'"'"',5'"'"'-dione.

10. A method for treating chronic complications of diabetes mellitus which comprises administering to a patient suffering from such complications of diabetes mellitus an effective amount for treating such complication, of a hydantoin derivative according to claim 1.

11. The method according to claim 10, wherein said chronic complications are one or more of diabetic cateracts, diabetic neuropathy, fine blood vessel lesions, diabetic retinopathy and arteriosclerotic blood vessel lesions.

9. A pharmaceutical composition for the treatment of chronic complications of diabetes mellitus comprising an effective amount for such treatment of a hydantoin derivative represented by the formula:

##STR19## wherein X₁ and X₂, which may be the same or different, independently represent a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group, Y represents an oxygen atom or sulfur atom, R₁ represents hydrogen and R₂ represents a lower alkyl group, and n represents 0 or 1, or a pharmaceutically acceptable salt thereof and a pharmaceutical carrier.