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-2020383973-A1
Application number	US-202016934055-A
Country	US
Kind code	A1
Filing date	Jul 21, 2020
Priority date	Jul 13, 2016
Publication date	Dec 10, 2020
Grant date	—

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

1 . A method for preventing and/or 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 (I):

or a pharmaceutically acceptable salt and/or solvate thereof, wherein:
Het is a nitrogen-containing heterocycloalkyl;
X is a single bond, a (C 1 -C 6 )alkyl group or a (C 1 -C 6 )alkoxy group;
Y is a group selected from —R 10 C(O)NHR 11 ; —R 10 C(O)NR 11 ; (C 1 -C 6 )alkyl; or (C 1 -C 6 )alkyl-aryl with (C 1 -C 6 )alkyl optionally substituted with ═O, ═S or a phenyl and with aryl optionally substituted with one or several substituents selected from hydrogen atom, halo, —CN, —NO 2 , —OR 12 , —NR 13 R 14 , —C(O)OR 15 , —C(O)NR 16 R 17 , —S(O) 2 NR 18 R 19 , —S(O) 2 R 20 , —NHS(O) 2 R 21 , —NHC(O)R 22 , 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, —OR 23 or —OC(O)R 24 , or with two adjacent substituents which form together with the carbon atoms to which they are chemically linked an heterocycle;
R 1 to R 4 are, independently of one another, hydrogen atom or a group selected from halo, —NO 2 , —CN, —OR 25 , —NR 26 R 27 , —C(O)OR 28 , —S(O) 2 R 29 , or a (C 1 -C 6 )alkyl group optionally substituted with one or several groups selected from halo or —OR 30 ;
R 10 to R 30 are, independently of one another, hydrogen atom, halo, 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 31 ;
R 31 is hydrogen atom, halo or a (C 1 -C 6 )alkyl group.

2 . The method of claim 1 , wherein Y is (C 1 -C 6 )alkyl-phenyl optionally substituted with one or several substituents, selected from hydrogen atom, halo, —CN, —NO 2 , —OR 12 , —NR 13 R 14 , —C(O)NR 16 R 17 , —S(O) 2 NR 18 R 19 , or a group selected from (C 1 -C 6 )alkyl, aryl, (C 1 -C 6 )alkyl-aryl, heterocycle or (C 1 -C 6 )alkyl-heterocycle.

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

or a pharmaceutically acceptable salt and/or solvate thereof, wherein:
Het is a nitrogen-containing heterocycloalkyl; and
R 1 to R 9 are as defined in claim 1 .

4 . The method of claim 1 , wherein Het is a piperazinyl or a piperidinyl.

5 . The 4 method of claim 1 , wherein said compound is a compound of the following general formula (Ib):

or a pharmaceutically acceptable salt and/or solvate thereof, R 1 to R 9 being as defined in claim 1 .

6 . The method of claim 1 , wherein R 1 to R 4 are, independently of one another, hydrogen atom or a group selected from halo, —NO 2 , —CN, —OR 25 , —NR 26 R 27 or a (C 1 -C 6 )alkyl group R 25 to R 27 being as defined in claim 1 .

7 . The method of claim 1 , wherein R 5 to R 9 are, independently of one another, hydrogen atom, halo, —CN, —NO 2 , —OR 12 , —NR 13 R 14 , —C(O)NR 16 R 17 , —S(O) 2 NR 18 R 19 , or a group selected from (C 1 -C 6 )alkyl, aryl, (C 1 -C 6 )alkyl-aryl, heterocycle or (C 1 -C 6 )alkyl-heterocycle; R 13 to R 19 being as defined claim 1 .

8 . The method of claim 1 , wherein R 10 to R 30 are, independently of one another, hydrogen atom, halo, or a group selected from (C 1 -C 6 )alkyl.

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

or a pharmaceutically acceptable salt and/or solvate thereof.

10 .- 17 . (canceled)

18 . A method for preventing and/or 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.

19 . The method of claim 18 , wherein said composition further comprises another active principle, such as topical antibiotic (erythromycine, dalacine), topical anti-inflammatory (benzoyl peroxydes derivatives), topical anti-seborrheic (isotretinoin, tretinoin, adapalene), zinc derivatives (zinc gluconate), cyclins, or isotretinoin.

20 . 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.

21 . The method of claim 1 , wherein said compound is the dihydrochloride salt of compound (Ic):

22 . The method of claim 18 , 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.

Assignees

• Univ Paris Descartes
• Hopitaux Paris Assist Publique
• Inst Nat Sante Rech Med
• Centre National De La Rescherche Scient Cnrs
• Sorbonne Unversite
• 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

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61P17/10

  Anti-acne agents · CPC title

• A61K31/495 Primary

  having six-membered rings with two {or more} nitrogen atoms as the only ring heteroatoms, e.g. piperazine {or tetrazines}(A61K31/48 takes precedence {; with three nitrogen atoms A61K31/53}) · CPC title

• C07D253/075

  Two hetero atoms, in positions 3 and 5 · CPC title