New lipophenol compounds and uses thereof

Patent metadata

Field	Value
Publication number	US-2018273554-A1
Application number	US-201815972282-A
Country	US
Kind code	A1
Filing date	May 7, 2018
Priority date	Apr 24, 2014
Publication date	Sep 27, 2018
Grant date	—

Abstract

The present invention relates to a compound of formula (I) wherein:—i is 0 or 1; j is 0 or 1; k is 0 or 1;—R 1 and R 2 are in particular H, (C 1 -C 12 )alkyl, or a group of formula C(O)R;—R is a, linear or branched, alkyl radical, comprising at least 19 carbon atoms;—R 3 is H and k=0 when j=1; or, when j=0, R 3 is —C(O)R or -L-C(O)R;—L, U and L″ are linkers; wherein, when j=0, at least one of the groups R 1 ; R 2 and R 3 comprises a radical R.

First claim

1 - 19 . (canceled)

20 . A method for treating a pathology involving both carbonyl and oxidative stress, comprising a step of administering to a patient in need thereof a pharmaceutically acceptable amount of a compound of formula (I):

wherein:
i is 0 or 1;
j is 0 or 1;
k is 0 or 1;
R 1 is chosen from the group consisting of: H, (C 1 -C 12 )alkyl, (C 3 -C 6 )cycloalkyl, and (C 6 -C 10 )aryl radicals; or R 1 may form a heterocycloalkyl radical with the oxygen atom bearing it; or R 1 is a group of formula C(O)R, R being as defined below;
R 2 is chosen from the group consisting of: H, (C 1 -C 12 )alkyl, (C 3 -C 6 )cycloalkyl, and (C 6 -C 10 )aryl radicals; or R 2 may form a heterocycloalkyl radical with the oxygen atom bearing it; or R 2 is a group of formula C(O)R, R being as defined below;
R is a, linear or branched, alkyl radical, possibly interrupted by one or several double bonds, comprising at least 19 carbon atoms, and wherein one or several hydrogen atoms may be replaced by deuterium atoms;
R 3 is H and k=0 when j=1; or, when j=0, R 3 is a group of formula —C(O)R

or
L-C(O)R, R being as defined above;
L is a linker having one of the following formulae (L1) or (L2):

wherein:
A 1 is an alkylene radical comprising from 3 to 6 carbon atoms;
A′ 1 is an alkylene radical comprising from 1 to 6 carbon atoms, optionally interrupted by one or several heteroatoms, such as oxygen atoms;
X 1 is a radical —C(O)— or an alkylene radical comprising from 1 to 6 carbon atoms;
X 2 is a radical —C(O)— or an alkylene radical comprising from 1 to 6 carbon atoms;
X′ 1 is chosen from the group consisting of: —O—, —N(R a )— or an alkylene radical comprising from 1 to 6 carbon atoms, optionally interrupted by one or several heteroatoms, such as oxygen atoms, R a being H or an alkyl group comprising from 1 to 6 carbon atoms;
L′ is a linker of formula -(A) p -(X) q —C(O)—, wherein:
p is 0 or 1;
q is 0 or 1;
A is an alkylene radical comprising from 1 to 6 carbon atoms, optionally interrupted by one or several heteroatoms, such as oxygen atoms,
X is —O—, —N(R b )— or an alkylene radical comprising from 1 to 6 carbon atoms, R b being H or an alkyl group comprising from 1 to 6 carbon atoms;

L″ is a linker chosen from the group consisting of: (C 6 -C 10 )arylene, (C 1 -C 12 )alkylene, (C 1 -C 12 )alkylene-(C 6 -C 10 )arylene, (C 6 -C 10 )arylene-(C 1 -C 12 )alkylene, —CH═CH-(C 6 -C 10 )arylene and (C 1 -C 12 )alkylene-CH═CH-(C 6 -C 10 )arylene radicals;

wherein, when j=0, at least one of the groups R 1 , R 2 and R 3 comprises a radical R;
provided that the compound of formula (I) is other than the following compound:

or its pharmaceutically acceptable salts, racemates, diastereomers or enantiomers.

21 . The method of claim 20 , wherein, in formula (I), when j=0, at most one of the groups R 1 , R 2 and R 3 is H.

22 . The method of claim 20 , comprising a step of administering a compound having the following formula (I-1):

wherein L′, R and R 2 are as defined in claim 20 ,

or its pharmaceutically acceptable salts, racemates, diastereomers or enantiomers.

23 . The method of claim 20 , comprising a step of administering a compound having the following formula (I-2):

wherein k, L″, R 1 and R 3 are as defined in claim 20 ,

or its pharmaceutically acceptable salts, racemates, diastereomers or enantiomers.

24 . The method of claim 23 , wherein, in formula (I-2), R 1 is an alkyl group.

25 . The method of claim 20 , comprising a step of administering a compound having the following formula (I-2-1):

wherein Alk is a (C 1 -C 12 )alkyl group, and R is as defined in claim 20 ,

or its pharmaceutically acceptable salts, racemates, diastereomers or enantiomers.

26 . The method of claim 20 , comprising a step of administering a compound having the following formula (I-3):

wherein A 1 , X 1 , X 2 , R, and R 1 are as defined in claim 20 ,

or its pharmaceutically acceptable salts, racemates, diastereomers or enantiomers.

27 . The method of claim 20 , comprising a step of administering a compound having the following formula (I-4):

wherein R is as defined in claim 20 ,
and R 1 is an alkyl group comprising from 1 to 12 carbon atoms,

or its pharmaceutically acceptable salts, racemates, diastereomers or enantiomers.

28 . The method of claim 20 , comprising a step of administering a compound having the following formula (I-4-2):

wherein R is as defined in claim 20 ,

or its pharmaceutically acceptable salts, racemates, diastereomers or enantiomers.

29 . The method of claim 20 , wherein, in formula (I), R 1 is a (C 1 -C 12 )alkyl group.

30 . The method of claim 20 , wherein, in formula (I), R 1 is a (C 1 -C 6 )alkyl group

31 . The method of claim 20 , wherein, in formula (I), R 1 is an isopropyl group.

32 . The method of claim 20 , wherein, in formula (I), R is a linear or branched alkyl group, possibly interrupted by one or several double bonds, comprising from 19 to 23 carbon atoms.

33 . The method of claim 20 , wherein, in formula (I), R is a linear or branched alkyl group, possibly interrupted by one or several double bonds, comprising from 19 to 23 carbon atoms, and wherein one or several hydrogen atoms are replaced by deuterium atoms.

34 . The method of claim 20 , wherein, in formula (I), R is a linear or branched alkyl group, interrupted by at least one double bond, comprising from 19 to 21 carbon atoms.

35 . The method of claim 20 , wherein, in formula (I), R is the following radical:

36 . The method of claim 20 , wherein, in formula (I), R is the following radical:

37 . The method of claim 20 , wherein the pathology involving carbonyl and oxidative stress is chosen from the group consisting of: inflammatory and infectious diseases, cardiovascular diseases, metabolic diseases, cancer, retinal pathologies, and neurodegenerative diseases.

38 . The method of claim 20 , wherein the pathology involving both carbonyl and oxidative stress is chosen from the group consisting of: atherosclerosis, type II diabetes, cancer, Alzheimer's disease, Parkinson's disease, Age-related Macular Degeneration (AMD), Stargardt disease, and severe influenza viruses.

Assignees

• Inst Nat Sante Rech Med
• Ct Hospitalier Universitaire Montpellier
• Univ Dauvergne
• Univ Montpellier

Inventors

• Brabet Philippe
• Cia David
• Guillou Laurent
• Hamel Christian
• Vigor Claire
• Durand Thierry
• Crauste Céline
• Vercauteren Joseph

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07B2200/05

  Isotopically modified compounds, e.g. labelled · CPC title

• C07F9/106

  Adducts, complexes, salts of phosphatides · CPC title

• C07B59/004

  Acyclic, carbocyclic or heterocyclic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen, sulfur, selenium or tellurium · CPC title

• A61P29/00

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