Method for preparing creatine fatty esters, creatine fatty esters thus prepared and uses thereof

Patent metadata

Field	Value
Publication number	US-10144705-B2
Application number	US-201314418418-A
Country	US
Kind code	B2
Filing date	Jul 17, 2013
Priority date	Jul 30, 2012
Publication date	Dec 4, 2018
Grant date	Dec 4, 2018

Abstract

The present invention concerns a method for preparing a creatine fatty ester or derivative thereof comprising at least one step consisting in reacting a diprotected creatinine with a molecule bearing at least one alcohol functional group and of formula R′—OH in which R′ represents a hydrocarbon radical containing at least 4 carbon atoms. The present invention also concerns particular creatine fatty esters or derivative thereof and medical uses thereof.

First claim

The invention claimed is:

1. A method for preparing a creatine fatty ester or derivative thereof comprising:
at least one step including reacting a diprotected creatinine with a molecule bearing at least one alcohol functional group and of formula (I):
R′—OH  (I)

in which R′ is a hydrocarbon radical containing at least 4 carbon atoms,
wherein the diprotected creatinine includes two protecting groups each replacing a hydrogen atom substituent of a nitrogen atom of the diprotected creatinine, the two protecting groups being identical or different,
wherein the creatine fatty ester derivative has a carboxylic acid group (—COOH) replacing at least one hydrogen atom of the methylguanidinyl group of the creatine fatty ester, and
wherein the creatine fatty ester derivative is obtained after a partial deprotection of a diprotected creatinine, the protecting groups of which are formula —C(O)—OR 4 with R 4 being a hydrocarbon group.

2. The method according to claim 1 , wherein the radical R′ is chosen from the group consisting of an alkyl radical with 4 to 30 carbon atoms, an alkenyl radical with 4 to 30 carbon atoms, and an aryl radical with 6 to 30 carbon atoms.

3. The method according to claim 1 , wherein the radical R′ is of the following formula (VIII):
—CH 2 —R′ 1   (VIII)

in which R′ 1 is a hydrocarbon radical containing at least 3 carbon atoms.

4. The method according to claim 1 , wherein the radical R′ is a glucosyl radical optionally substituted.

5. The method according to claim 1 , wherein said method comprises the following successive steps:
a) reacting creatinine with a protective agent to obtain the diprotected creatinine;
b) reacting the diprotected creatinine obtained at step (a) with a molecule bearing at least one alcohol functional group and of formula (I) to obtain a diprotected creatine fatty ester; and
c) deprotecting the diprotected creatine fatty ester obtained at step (b), in order to obtain said creatine fatty ester or derivative thereof.

6. The method according to claim 5 , wherein said protective agent is of formula (XII):
Cl—C(O)—OR 4   (XII)

in which the radical R 4 is a hydrocarbon group.

7. The method according to claim 5 , wherein a solvent in a solution containing the creatinine and the protective agent implemented at step (a) is dichloromethane (DCM).

8. The method according to claim 5 , wherein a solution containing the creatinine and the protective agent implemented at step (a) contains the Hünig's base or N,N-diisopropyl ethylamine (DIEPA).

9. The method according to claim 5 , wherein, at step (b), for one equivalent of the diprotected creatinine, the amount of molecule bearing at least one alcohol functional group and of formula (I) expressed in equivalents is between 1 and 15.

10. The method according to claim 5 , wherein said step (b) is carried out during 1 to 20 h.

11. The method according to claim 5 , wherein said step (b) is carried out at a temperature between 60 and 100° C.

12. A compound prepared by a method according to claim 1 , said compound having the formula (III), (IV) or (V):
(NH 2 )—C(NH)—N(CH 3 )—CH 2 —COOR′  (III)

in which
radical R′ is a glucosyl radical optionally substituted, or a salt thereof.

13. A composition comprising at least one compound according to claim 12 , in an acceptable vehicle, wherein said composition is a food additive or a nutritional supplement.

14. A pharmaceutical, diagnostic or imaging composition comprising at least one compound according to claim 12 , in an acceptable pharmaceutical vehicle.

15. A method for treating or preventing at least one disease, disorder, or condition selected from the group consisting of hypoxia and ischemic brain disease, comprising administering to a subject in need, a therapeutic amount of a compound according to claim 12 .

16. A method for treating or preventing at least one disease, disorder or condition selected from the group consisting of hypoxia and ischemic brain disease, comprising administering to a subject in need, a therapeutic amount of a compound according to claim 14 .

17. The method according to claim 9 , wherein the amount of molecule bearing at least one alcohol functional group and of formula (I) expressed in equivalent is between 1 and 10.

18. The method according to claim 10 , wherein said step (b) is carried out during 2 to 16 h.

19. The method according to claim 18 , wherein said step (b) is carried out during 2 to 10 h.

20. The method according to claim 11 , wherein said step (b) is carried out at a temperature between 70 and 90° C.

21. The method according to claim 20 , wherein said step (b) is carried out at a temperature at around 80° C. (i.e. 80° C.±5° C.).

Assignees

• Commissariat Energie Atomique

Inventors

• Dezard Sophie
• Taran Frederic
• Trotier-Faurion Alexandra
• Mabondzo Aloise

Classifications

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title

• A61P25/14

  for treating abnormal movements, e.g. chorea, dyskinesia · CPC title