Meclozine derivatives and diclazuril derivatives for use in the prevention and/or the treatment of disorders associated to the inflammation induced by P. acnes

Patent metadata

Field	Value
Publication number	US-11116763-B2
Application number	US-201716317091-A
Country	US
Kind code	B2
Filing date	Jul 13, 2017
Priority date	Jul 13, 2016
Publication date	Sep 14, 2021
Grant date	Sep 14, 2021

Abstract

The present invention relates to compounds of the following general formula (I) or (II) or a pharmaceutically acceptable salt and/or solvate thereof, for use in the prevention and/or the treatment of disorders associated to the inflammation induced by P. acnes, in particular in the prevention and/or the treatment of acne, psoriasis, chronic urticaria, urticaria pigmentosa, cutaneous autoinflammatory diseases, hidradenitis or atopic dermatis.

First claim

The invention claimed is:

1. A method for treating disorders associated to the inflammation induced by P. acnes comprising administering to a subject in need thereof an effective amount of a compound of following general formula (II):

or a pharmaceutically acceptable salt and/or solvate thereof, wherein:
X′, Y′ and Z′ are, independently of one another, CH, CH 2 , NH or N;
W′ is CHR′3, S═O or S;
R′ 1 and R′ 2 are, independently of one another, hydrogen atom, halo, —CN, —NO 2 , —CF 3 , —OR′ 7 , —NR′ 8 R′ 9 , or a (C 1 -C 6 )alkyl group;
R′ 3 is H, —CN, OR′ 10 , or a (C 1 -C 6 )alkyl group;
R′ 4 and R′ 5 , are, independently of one another, hydrogen atom or a group selected from halo, —NO 2 , —CN, —OR′ 11 , —NR′ 12 R′ 13 , —C(O)OR′ 14 , —S(O) 2 R′ 15 , or a (C 1 -C 6 )alkyl group optionally substituted with one or several groups selected from halo or —OR′ 16 ;
R′ 7 to R′ 16 are, independently of one another, hydrogen atom or a group selected from (C 1 -C 6 )alkyl, aryl, (C 1 -C 6 )alkyl-aryl, heterocycle, (C 1 -C 6 )alkyl-heterocycle, said group being optionally substituted with one or several groups selected from halo, (C 1 -C 6 )alkyl, CF 3 or —OR′ 17 ;
R′ 17 is hydrogen atom, halo or a (C 1 -C 6 )alkyl group.

2. The method of claim 1 , wherein said compound is a compound of the following general formula (IIa):

or a pharmaceutically acceptable salt and/or solvate thereof, wherein:
X′, Y′ and Z′ are, independently of one another, CH, CH 2 , NH, or N;
R′ 1 and R′ 2 are, independently of one another, hydrogen atom, halo, —CN, —NO 2 , —CF 3 , —OR′ 7 , —NR′ 8 R′ 9 , or a (C 1 -C 6 )alkyl group;
R′ 3 is H, —CN, OR′ 10 , or a (C 1 -C 6 )alkyl group;
R′ 4 and R′ 5 , are, independently of one another, hydrogen atom or a group selected from halo, —NO 2 , —CN, —OR′ 11 , —NR′ 12 R′ 13 , —C(O)OR′ 14 , —S(O) 2 R′ 15 , or a (C 1 -C 6 )alkyl group optionally substituted with one or several groups selected from halo or —OR′ 16 ;
R′ 7 to R′ 16 are, independently of one another, hydrogen atom, or a group selected from (C 1 -C 6 )alkyl, aryl, (C 1 -C 6 )alkyl-aryl, heterocycle, (C 1 -C 6 )alkyl-heterocycle, said group being optionally substituted with one or several groups selected from halo, (C 1 -C 6 )alkyl, CF 3 or —OR′ 17 ;
R′ 17 is hydrogen atom, halo or a (C 1 -C 6 )alkyl group.

3. The method of claim 1 , wherein X′, Y′, and Z′ are each a nitrogen atom.

4. The method of claim 1 , wherein R′ 3 is —CN, or OH.

5. The method of claim 1 , wherein and R′ 1 and R′ 2 are, independently of one another, hydrogen atom, halo, —CF 3 , —OH, or a (C 1 -C 6 )alkyl group.

6. The method of claim 1 , wherein R′ 5 is an hydrogen atom and R′ 4 is selected from the group consisting of hydrogen atom, halo, —CF 3 , —OH, and a (C 1 -C 6 )alkyl group.

7. The method of claim 1 , wherein said compound is a compound of the following general formula (IIb):

or a pharmaceutically acceptable salt and/or solvate thereof.

8. The method of claim 1 , wherein said compound is a compound of the following formula (IId):

or a pharmaceutically acceptable salt and/or solvate thereof.

9. The method of claim 1 , wherein said disorders associated to the inflammation induced by P. acnes are acne, psoriasis, chronic urticaria, urticaria pigmentosa, cutaneous autoinflammatory diseases, hidradenitis, or atopic dermatis.

10. A method for treating disorders associated to the inflammation induced by P. acnes comprising administering to a subject in need thereof an effective amount of a pharmaceutical composition comprising at least one compound of claim 1 and at least one pharmaceutically acceptable excipient.

11. The method of claim 10 , wherein said composition further comprises another active principle selected from the group consisting of a topical antibiotic, topical anti-inflammatory, topical anti-seborrheic zinc derivative, cyclin, and isotretinoin.

12. The method of claim 10 , wherein said composition further comprises another active principle selected from the group consisting of erythromycine, dalacine, benzoyl peroxyde derivatives, isotretinoin, tretinoin, adapalene, zinc gluconate, cyclins, and isotretinoin.

Assignees

• Univ Paris
• Assist Publique—Hopitaux De Paris
• Inst Nat Sante Rech Med
• Centre Nat Rech Scient
• Univ Sorbonne

Inventors

• Dupin Nicolas
• Calvez Vincent
• Grange Philippe
• Marcelin Anne-Geneviève

Classifications

• A61K31/53 Primary

  having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine (melarsoprol A61K31/555 {; with four nitrogen atoms A61K31/495}) · CPC title

• A61K31/202

  having three or more double bonds, e.g. linolenic (eicosanoids, e.g. leukotrienes A61K31/557) · CPC title

• C07D295/06 Primary

  substituted by halogen atoms or nitro radicals · CPC title

• A61P17/06

  Antipsoriatics · CPC title

• A61P17/10

  Anti-acne agents · CPC title