Tocotrienol derivatives, pharmaceutical composition and method of use in 5-lipoxygenase related diseases

Patent metadata

Field	Value
Publication number	US-10494357-B2
Application number	US-201615755244-A
Country	US
Kind code	B2
Filing date	Aug 26, 2016
Priority date	Aug 27, 2015
Publication date	Dec 3, 2019
Grant date	Dec 3, 2019

Abstract

The present invention relates to compounds of formula (III)

or to compounds of formula (IV)

wherein R 1 , R 2 , R 3 and R 4 are as defined in the claims, and their use in therapeutic treatments of 5-lipoxygenase related diseases such as chronic airway inflammatory or dermatological disorders.

First claim

The invention claimed is:

1. A tocotrienol derivative of general formula (IV)

and pharmaceutically acceptable salts and/or solvates thereof, wherein:
* stands for the (R)-enantiomer, the (S)-enantiomer, for the racemate or for the non-racemic mixture of (R) and (S) enantiomers of the corresponding formula (IV);
R 2 is H or alkyl; R 3 and R 4 are identical or different and each one is selected from the group of amido, alkyl, carboxyl, hydroxyl and formyl; and
wherein at least one of R 3 or R 4 is an alkyl substituted by at least one group selected from hydroxyl, carboxyl or formyl.

2. The tocotrienol derivative according to claim 1 , wherein the tocotrienol derivative is the (R)-enantiomer.

3. The tocotrienol derivative according to claim 1 , wherein R 2 is CH 3 .

4. The tocotrienol derivative according to claim 1 , wherein R 3 and R 4 are selected such that the stereochemistry of double bond C═C to which they are attached is (E).

5. The tocotrienol derivative according to claim 1 selected from:

6. A pharmaceutical composition comprising at least one tocotrienol derivative according to claim 1 , and at least one pharmaceutically acceptable carrier, diluent, excipient and/or adjuvant.

7. A medicament comprising at least one tocotrienol derivative according to claim 1 , or pharmaceutically acceptable salts and/or solvates thereof.

8. The tocotrienol derivative of claim 1 , wherein alkyl is substituted by at least one group selected from hydroxyl, carboxyl, oxo, amido, amino and formyl.

9. The tocotrienol derivative of claim 1 , wherein amido group is substituted by at least one group selected from alkyl, arylalkyl or alkylaryl.

10. The tocotrienol derivative of claim 8 , wherein amido group is substituted by at least one group selected from alkyl, arylalkyl or alkylaryl.

11. The tocotrienol derivative according to claim 9 , wherein the tocotrienol derivative is the (R)-enantiomer.

Assignees

• Univ Angers
• Univ Innsbruck
• Univ Jena Friedrich Schiller

Inventors

• Richomme Pascal
• Helesbeux Jean-Jacques
• Guilet David
• Seraphin Denis
• Stuppner Hermann
• Waltenberger Birgit
• Schuster Daniela
• Temml Veronika Sophie
• Koeberle Andreas
• Werz Oliver

Classifications

• A61P11/06

  Antiasthmatics · CPC title

• C07D311/72 Primary

  3,4-Dihydro derivatives having in position 2 at least one methyl radical and in position 6 one oxygen atom, e.g. tocopherols · CPC title