Process for treating an individual with an esthetic defect of skin by modulating SASPase FLG2 complex

Patent metadata

Field	Value
Publication number	US-9869681-B2
Application number	US-201113992589-A
Country	US
Kind code	B2
Filing date	Dec 5, 2011
Priority date	Dec 7, 2010
Publication date	Jan 16, 2018
Grant date	Jan 16, 2018

Abstract

The present invention relates to the use of a compound, suitable for modulating the interaction between first and second partner proteins, or between homologues, mutants, or fragments of said proteins, said first and second proteins being SASPase and filaggrin-2, or FLG2, as an active agent for treating and/or preventing aesthetic defects in the skin, and/or in the appendages thereof, linked to an imbalance in the differentiation and/or proliferation of the cells of the epidermis.

First claim

The invention claimed is:

1. A process for treating an individual with an esthetic defect of the skin, wherein said defect is at least one selected from the group consisting of signs of aging of the skin, a disorder of the epidermal barrier function, a skin desquamation disorder, a cicatrization and/or re-epithelialization defect, the process comprising:
administering to said individual an active agent comprising a compound that modulates the interaction between a first and a second partner protein, homologs, mutants or fragments of said proteins, wherein said first and second proteins are SASPase and filaggrin-2, or FLG2, and said compound is represented by formula (Ia) or (Ib):

wherein:
R 1 is H, a linear or branched, saturated or unsaturated C 1 -C 4 alkyl, or —C(O) R8, wherein R 8 is a linear or branched, saturated or unsaturated C 1 -C 4 alkyl;
R 2 is ═O, —OR 9 or —OC(O) R9, wherein R 9 is H or a saturated C 1 -C 2 alkyl;
R 3 , R 4 , R 5 , R 6 , and R 7 are each independently of each other H; —NO 2 ; —OH; a fluorine; —CF 3 ; a linear or branched, saturated or unsaturated C 1 -C 4 alkyl; a phenyl; —OC(O)—CH(Ph) 2 ; —O-Ph-X wherein X is H, —OH, —NO 2 , a fluorine, a linear or branched, saturated or unsaturated C 1 -C 4 alkyl or alkoxy; —O—S(O 2 )-Ph-Z wherein Z is a linear or branched, saturated or unsaturated C 1 -C 4 alkyl; —R 8 OH; —OR 9 ; —OC(O)R 9 , wherein R 8 is a linear or branched, saturated or unsaturated C 1 -C 4 alkyl and R 9 is H or a saturated C 1 -C 2 alkyl; —R 10 Ph, wherein R 10 is a linear or branched, saturated or unsaturated C 1 -C 4 alkylene; or —OC(O)—Y n —Ar 1 —(X) m , wherein
n is 0 or 1 and m is an integer ranging from 0 to 4, with the proviso that n and m are not simultaneously 0,
Y is a linear or branched, saturated or unsaturated C 1 -C 4 alkylene,
X is H, —OH, —NO 2 , a fluorine, a linear or branched, saturated or unsaturated C 1 -C 4 alkyl or alkoxy, and
Ar 1 is

wherein * is a bond with Y and @ is a bond with X,
and physiologically acceptable salts thereof.

2. The process of claim 1 , wherein R 1 is H, a methyl, an ethyl, a propyl, or —C(O) R8, wherein R 8 is a methyl, an ethyl, or a propyl.

3. The process of claim 1 , wherein R 2 is ═O or —OR 9 .

4. The process of claim 1 , wherein R 3 , R 4 , R 5 , R 6 , and R 7 are each independently of each other H; —OH; a fluorine; a methyl or an ethyl; a phenyl; —OC(O)—CH(Ph) 2 ; —O-Ph-X, wherein X is H, —OH, a fluorine, a methyl, an ethyl, a methoxy, or an ethoxy; —O—S(O 2 )-Ph-Z, wherein Z is a methyl or an ethyl; —R 8 OH; —OR 9 ; —OC(O)R 9 , wherein R 8 is a methyl or an ethyl and R 9 is H or a methyl; —R 10 Ph, wherein R 10 is a methylene or an ethylene, or —OC(O)—Y n —Ar 1 —(X) m .

5. The process of claim 1 , wherein not more than one from among R 3 , R 4 , R 5 , R 6 , and R 7 is a —OC(O)—Y n —Ar 1 —X m .

6. The process of claim 1 , wherein n is equal to 0,
m is equal to 1, X is a methyl or a methoxy, and Ar 1 is:

wherein * is a bond with Y and @ is a bond with X.

7. The process of claim 1 , wherein R 3 , R 5 , R 7 and R 4 or R 6 are each independently of each other H; —NO 2 ; —OH; a fluorine; a methyl or an ethyl; a phenyl; —R 8 OH; —OR 9 ; —OC(O) R9, wherein R 8 is a methyl or an ethyl and R 9 is H or a methyl; —R 10 Ph, wherein R 16 is a methylene or an ethylene.

8. The process of claim 1 , wherein said compound is represented by formula (II):

Assignees

• Bernard Dominique
• Thomas-Collignon Agnes
• Rozot Roger
• Muller Benoit
• Oreal

Inventors

• Bernard Dominique
• Thomas-Collignon Agnes
• Rozot Roger
• Muller Benoit

Classifications

• A61P17/00

  Drugs for dermatological disorders · CPC title

• G01N33/6845

  Methods of identifying protein-protein interactions in protein mixtures · CPC title

• G01N2500/02

  Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor) · CPC title

• A61Q19/08

  Anti-ageing preparations · CPC title

• A61Q15/00

  Anti-perspirants or body deodorants (deodorisation of air A61L9/00) · CPC title