Deuterated substituted dihydrofuranones and medicaments containing these compounds

• US 7,317,039 B2
• Filed: 12/11/2002
• Issued: 01/08/2008
• Est. Priority Date: 12/12/2001
• Status: Expired due to Fees

• Current Assignee: BBD Berolina Drug Development GmbH
• Original Assignee: BDD Berolina Drug Development GmbH
• Inventors: Alken, Rudolf-Giesbert
• Primary Examiner(s): DENTZ, BERNARD I
• Application Number:
  US10/498,709
• Publication Number:
  US 20050176814A1
• Time in Patent Office: 1,854 Days
• Field of Search: 549/295, 549/323, 514/461
• US Class Current: 514/461
• CPC Class Codes: A61K 31/365 Lactones
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 307/32 Oxygen atoms

Abstract

The invention concerns deuterated substituted dihydrofuranones and pharmaceuticals containing these compounds.

In addition, the invention concerns the use of deuterated substituted dihydrofuranones for the treatment of symptoms for the irritating states of degenerative joint disorders, of acute pain and primary dysmenorrhea.

In addition, the invention discloses pharmaceutical compositions, which contain deuterated substituted dihydrofuranones as well as their physiologically compatible salts, in addition to pharmaceutically compatible adjuvants and/or additives, for the treatment of symptoms for the irritating states of degenerative joint disorders, of acute pain and primary dysmenorrhea.

Claims

1. Deuterated substituted dihydrofuranones of the general formula I in concentrated form,

2. Deuterated substituted dihydrofuranones according to claim 1, wherein

R¹ is partially or completely deuterated methyl,

R², independent of one another, indicates H or D,

R³, independent of one another, is H or D, and

R⁴, independent of one another, indicates H or D.

3. Deuterated substituted dihydrofuranones according to claim 1, wherein

R¹ is methyl or partially or completely deuterated methyl,

R² indicates D,

R³, independent of one another, is H or D, and

R⁴, independent of one another, indicates H or D.

4. Deuterated substituted dihydrofuranones according to claim 1, wherein

R¹ is methyl or partially or completely deuterated methyl,

R², independent of one another, indicates H or D,

R³ is D and

R⁴, independent of one another, indicates H or D.

5. Deuterated substituted dihydrofuranones according to claim 1, wherein

R¹ is methyl or partially or completely deuterated methyl,

R², independent of one another, indicates H or D,

R³, independent of one another, is H or D, and

R⁴ indicates D.

6. Deuterated substituted dihydrofuranones according to claim 1, wherein

R¹ is partially or completely deuterated methyl,

R² D,

R³, independent of one another, is H or D, and

R⁴, independent of one another, indicates H or D.

7. Deuterated substituted dihydrofuranones according to claim 1, wherein

R¹ is partially or completely deuterated methyl,

R², independent of one another, indicates H or D,

R³ is D and

R⁴, independent of one another, indicates H or D.

8. Deuterated substituted dihydrofuranones according to claim 1, wherein

R¹ is partially or completely deuterated methyl,

R², independent of one another, indicates H or D,

R³, independent of one another, is H or D, and

R⁴ D.

9. Deuterated substituted dihydrofuranones according to claim 1, wherein

R¹ is methyl or partially or completely deuterated methyl,

R² and R³ are D and

R⁴, independent of one another, indicates H or D.

10. Deuterated substituted dihydrofuranones according to claim 1, wherein

R¹ is methyl or partially or completely deuterated methyl,

R² indicates D,

R³, independent of one another, is H or D, and

R⁴ indicates D.

11. Deuterated substituted dihydrofuranones according to claim 1, wherein

R¹ is methyl or partially or completely deuterated methyl,

R², independent of one another, indicates H or D, and

R³ R⁴ are D.

12. Deuterated substituted dihydrofuranones according to claim 1, wherein

R¹ is partially or completely deuterated methyl,

R² and R³ are D and

R⁴, independent of one another, indicates H or D.

13. Deuterated substituted dihydrofuranones according to claim 1, wherein R¹ is partially or completely deuterated methyl, R² indicates D, R³, independent of one another, is H or D, and R⁴ indicates D.

14. Deuterated substituted dihydrofuranones according to claim 1, wherein R¹ is partially or completely deuterated methyl, R², independent of one another, indicates H or D, and R³ and R⁴ indicate D.

15. Deuterated substituted dihydrofuranones according to claim 1, wherein R¹ is methyl or partially or completely deuterated methyl, and R², R³ and R⁴ indicate D.

16. Deuterated substituted dihydrofuranones according to claim 1, wherein R¹ is partially or completely deuterated methyl, and R², R³ and R⁴ indicate D.

17. Deuterated substituted dihydrofuranones according to claim 1, selected from the group consisting of d14-4-[4-(Methylsulfonyl)phenyl]-3-phenyl-2-(5H)-furanone;

4-[4-(Trideuteromethylsulfonyl)phenyl]-3 -phenyl-2-(5H)-furanone;

4-[4-(Methylsulfonyl)-d4-phenyl]-3-phenyl-2-(5H)-furanone;

4-[4-(Methylsulfonyl)phenyl]-3-d5-phenyl-2-(5H) furanone;

5,5-Dideutero-4-[4-(methylsulfonyl)phenyl]-3-phenyl-2-(5H)-furanone;

4-[d7-4-(Methylsulfonyl)phenyl]-3-phenyl-2-(5H)-furanone;

4-[4-(Trideuteromethylsulfonyl)phenyl]-3 -d5-phenyl-2-(5H)-furanone;

5,5-Dideutero-4-[4-(trideuteromethylsulfonyl)phenyl]-3-phenyl-2-(5H)-furanone;

4-[4-(Methylsulfonyl) -d4-phenyl]-3-d5-phenyl-2-(5H)-furanone;

5 ,5-Dideutero-4-[4-(methylsulfonyl) -d4-phenyl]-3-phenyl-2-(5H)-furanone;

5,5-Dideutero-4-[4-(methylsulfonyl)phenyl]-3-d5-phenyl-2-(5H)-furanone;

4-[4-(Trideuteromethylsulfonyl) -d4-phenyl]-3-d5-phenyl-2-(5H)-furanone;

5,5-Dideutero-4-[4-(trideuteromethylsulfonyl)-d5-phenyl]-3 -phenyl-2-(5H)-furanone;

5,5-Dideutero -4-[4-(trideuteromethylsulfonyl)phenyl]-3 -d5-phenyl-2-(5H)-furanone; and

, 5,5-Dideutero-4-[4-(methylsulfonyl)-d4-phenyl]-3 -d5-phenyl-2-(5H)-furanone.

18. A method of treating symptoms for the irritating states of degenerative joint disorders, of acute pain and primary dysmenorrhea comprising administering to a patient suffering therefrom a therapeutically effective amount of a deuterated substituted dihydrofuranone according to claim 1 or a physiologically compatible salt.

19. A method for producing a pharmaceutical for the treatment of symptoms for the irritating states of degenerative joint disorders, of acute pain and primary dysmenorrhea comprising combining (i) a therapeutically effective amount of a deuterated substituted dihydrofuranone according to claim 1 or a physiologically compatible salt and (ii) a pharmaceutically compatible vehicle.

20. Pharmaceutical composition, which contains a therapeutically effective amount of a deuterated substituted dihydrofuranone according to claim 1 or a physiologically compatible salt, in addition to pharmaceutically compatible adjuvants and/or additives, for the treatment of symptoms for the irritating states of degenerative joint disorders, of acute pain and primary dysmenorrhea.