Ustilipides, method for the production and the use thereof

• US 6,472,158 B1
• Filed: 07/21/2000
• Issued: 10/29/2002
• Est. Priority Date: 01/23/1998
• Status: Expired due to Fees

• Current Assignee: Sanofi-Aventis Deutschland GmbH (Sanofi )
• Original Assignee: Aventis Pharma Deutschland GmbH (Sanofi )
• Inventors: Noelken, Gerhard, Kurz, Michael, Wink, Joachim, Vértesy, Laszló
• Primary Examiner(s): Horlick, Kenneth R.
• Assistant Examiner(s): MAUPIN, CHRISTINE L
• Application Number:
  US09/600,759
• Time in Patent Office: 830 Days
• Field of Search: 435/7.1, 435/91.4, 435/6, 435/91.1, 435/254.1, 536/500, 514/2, 514/183
• US Class Current: 435/7.1
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: C07H 15/04 attached to an oxygen atom of the saccharide radical
• CPC Class Codes: C12P 19/44 Preparation of O-glycosides, e.g. glucosides polysaccharides and not substituted disaccharides C12P19/04, C12P19/12

Abstract

New active agents (ustilipides) formed by the microorganism Ustilago maydis, FH 2634, DSM 11494 during fermentation. The invention also relates to a method for the production of said ustilipides and to their use as medicaments in the treatment of schizophrenia or diseases caused by dopamine metabolic dysfunction. The invention further relates to medicaments containing ustilipides and to the microorganism Ustilago maydis, FH 2634, DSM 11494.

Claims

1. A compound of the formula I

where

R₂, R₃ and R₄ are, independently of one another, acyl radicals with 2-25 carbon atoms, which are unsubstituted or are substituted, independently of one another, by 1, 2 or 3 (C₆-C₁₂)-aryl radicals;

and

R is hydrogen or a radical defined under R², R³ and R⁴,

where in the case where R is hydrogen, then R² is an acyl radical with 3-25 carbon atoms, which is unsubstituted or substituted by 1, 2 or 3 (C₆-C₁₂)-aryl radicals;

or a physiologically tolerated salt thereof.

2. A compound as claimed in claim 1, in which:

R is hydrogen or an acyl radical with 2-25 carbon atoms;

R² is an acyl radical with 4-25 carbon atoms;

R³ is an acyl radical with 10-25 carbon atoms; and

R⁴ is an acyl radical with 2-25 carbon atoms;

or a physiologically tolerated salt thereof.

3. A method for the production of a compound as claimed in claim 1, which comprises fermenting the microorganism Ustilago maydis DSM 11494 or one of its variants or mutants under suitable conditions to obtain ustilipides, isolating one or more of the ustilipides, and converting the latter where appropriate into physiologically tolerated salts.

4. The method as claimed in claim 3, wherein the fermentation is carried out under aerobic conditions at a temperature between 20 and 35°

C. and at a pH between 3 and 10.

5. A method for antagonizing the dopamine D2 and/or dopamine D3 receptor, which comprises contacting the D2 and/or D3 receptor with a compound as claimed in claim 1.

6. A method for the treatment of schizophrenia or other disorder caused by dysfunction of dopamine metabolism, which comprises administering to a host in need of the treatment an effective amount of a compound as claimed in claim 1.

7. A pharmaceutical, which comprises an effective amount of at least one compound as claimed in claim 1, and a carrier.

8. A compound of the formula (II)

where n is 11;

or a physiologically tolerated salt thereof.

9. A method for the production of a compound as claimed in claim 8, which comprises fermenting the microorganism Ustilago maydis DSM 11494 or one of its variants or mutants under suitable conditions to obtain ustilipides, isolating one or more of the ustilipides, and converting the latter where appropriate into physiologically tolerated salts.

10. The method as claimed in claim 9, wherein the fermentation is carried out under aerobic conditions at a temperature ranging from 20 to 35°

C. and at a pH between 3 and 10.

11. A method for antagonizing the dopamine D2 and/or dopamine D3 receptor, which comprises contacting the D2 and/or D3 receptor with a compound as claimed in claim 8.

12. A method for the treatment of schizophrenia or other disorder caused by dysfunction of dopamine metabolism, which comprises administering to a host in need of the treatment an effective amount of a compound as claimed in claim 8.

13. A pharmaceutical, which comprises an effective amount of at least one compound as claimed in claim 8, and a carrier.

14. A compound of the formula (III)

where n is 11;

or a physiologically tolerated salts thereof.

15. A method for the production of a compound as claimed in claim 14 which comprises fermenting the microorganism Ustilago maydis DSM 11494 or one of its variants or mutants under suitable conditions to obtain ustilipides, isolating one or more of the ustilipides, and converting the latter where appropriate into physiologically tolerated salts.

16. The method as claimed in claim 15, wherein the fermentation is carried out under aerobic conditions at a temperature ranging from 20 to 35°

C. and at a pH between 3 and 10.

17. A method for antagonizing the dopamine D2 and/or dopamine D3 receptor, which comprises contacting the D2 and/or D3 receptor with a compound as claimed in claim 14.

18. A method for the treatment of schizophrenia or other disorder caused by dysfunction of dopamine metabolism, which comprises administering to a host in need of the treatment an effective amount of a compound as claimed in claim 14.

19. A pharmaceutical, which comprises an effective amount of at least one compound as claimed in claim 14, and a carrier.

20. A compound of the formula (IV)

where n is 11;

or a physiologically tolerated salt thereof.

21. A method for the production of a compound as claimed in claim 20, which comprises fermenting the microorganism Ustilago maydis DSM 11494 or one of its variants or mutants under suitable conditions to obtain ustilipides, isolating one or more of the ustilipides, and converting the latter where appropriate into physiologically tolerated salts.

22. The method as claimed in claim 21, wherein the fermentation is carried out under aerobic conditions at a temperature ranging from 20 to 35°

C. and at a pH between 3 and 10.

23. A method for antagonizing the dopamine D2 and/or dopamine D3 receptor, which comprises contacting the D2 and/or D3 receptor with a compound as claimed in claim 20.

24. A method for the treatment of schizophrenia or other disorder caused by dysfunction of dopamine metabolism, which comprises administering to a host in need of the treatment an effective amount of a compound as claimed in claim 20.

25. A pharmaceutical, which comprises an effective amount of at least one compound as claimed in claim 20, and a carrier.

26. The isolated microorganism Ustilago maydis DSM 11494.