Multimeric mannosides, a process for preparing the same and their uses as a drug

Patent metadata

Field	Value
Publication number	US-10273313-B2
Application number	US-201314416529-A
Country	US
Kind code	B2
Filing date	Jul 24, 2013
Priority date	Jul 24, 2012
Publication date	Apr 30, 2019
Grant date	Apr 30, 2019

Abstract

The present invention relates to multimeric mannosides, a process for preparing the same and their uses in medicine for treating Escherichia coli infections. Exemplary compounds are:

First claim

The invention claimed is:

1. A compound of the following formula (I):
A-X n   (I)

wherein:
A is selected from the group consisting of:

wherein
X′ is selected from the group consisting of —OH and -----, wherein ----- represents a bond to X;
R 2 is selected from the group consisting of hydrogen and a linear or branched (C 1 -C 7 )-alkyl;
n is an integer from 6 to 8;
X represents a group according to formula (1):
-W p -L r -Y s —Z  (1)

wherein:
p, r, and s are integers independently from each other equal to 0 or 1,

provided that:
when r is equal to 0, p and s are such as the sum p+s is equal to 1,
when r is equal to 1, p and s are such as the sum p+s is equal to 2;

W is selected from the group consisting of:

Y is selected from the group consisting of:

Z is selected from the group consisting of:

L represents a linker having a formula:

m being an integer comprised from 0 to 20,
q being an integer chosen from 6, 7, and 8,
Q and Q′ representing independently from each other NH, O or S;
T representing O, S or CH 2 ;
R′ representing a group selected from the group consisting of:
a linear or branched (C 1 -C 7 )-alkane diyl,
a linear or branched (C 2 -C 7 )-alkene diyl,
a linear or branched (C 2 -C 7 )-alkyne diyl,
a (C 3 -C 7 )-cycloalkane diyl,
a (C 5 -C 7 )-cycloalkene diyl,
a (C 3 -C 7 )-heterocycloalkane diyl,
a (C 5 -C 7 )-heterocycloalkene diyl,
an arene diyl, said arene being an aromatic or heteroaromatic group,
a group -arene 1 -arene 2 - wherein arene 1 and arene 2 are independently to each other an aromatic or heteroaromatic arene; and
a group of the following formula:

said (C 1 -C 7 )-alkane diyl, (C 2 -C 7 )-alkene diyl, (C 2 -C 7 )-alkyne diyl, (C 3 -C 7 )-cycloalkane diyl, (C 5 -C 7 )-cycloalkene diyl, (C 3 -C 7 )-heterocycloalkane diyl, (C 5 -C 7 )-heterocycloalkene diyl, arene diyl, arene 1 and arene 2 being substituted or not by one or more substituent(s), each independently selected from the group consisting of:
a linear or branched (C 1 -C 7 )-alkyl,
a linear or branched (C 2 -C 7 )-alkenyl,
a linear or branched (C 2 -C 7 )-alkynyl,
a (C 3 -C 7 )-cycloalkyl,
a (C 5 -C 7 )-cycloalkenyl,
a (C 3 -C 7 )-heterocycloalkyl,
a (C 5 -C 7 )-heterocycloalkenyl,
an aryl, wherein the aryl is an aromatic or heteroaromatic group
an alkyl aryl, wherein the aryl is an aromatic or heteroaromatic group,
a CHO,
a CO—(C 1 -C 7 )-alkyl,
a CO-aryl, wherein aryl is an aromatic or heteroaromatic group,
a CO 2 H,
a CO 2 —(C 1 -C 7 )-alkyl,
a CONH—(C 1 -C 7 )-alkyl,
a halogen selected from the group consisting of F, Cl, Br, and I,
CF 3 ,
OR a , wherein R a represents:
H, a linear or branched (C 1 -C 7 )-alkyl, a (C 3 -C 7 )-cycloalkyl, CO—(C 1 -C 7 )-alkyl, or CO-aryl, wherein aryl is an aromatic or heteroaromatic group,

NR b R c , wherein R b and R c represent independently from each other:
H, a linear or branched (C 1 -C 7 )-alkyl, a (C 3 -C 7 )-cycloalkyl, CO—(C 1 -C 7 )-alkyl, or CO-aryl, wherein aryl is an aromatic or heteroaromatic group,

NO 2 and
CN.

2. The compound according to claim 1 , of formula (I):
A-X n   (I)

wherein A is a cyclodextrin chosen from α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), γ-cyclodextrin (γ-CD), n being 6 when A is α-cyclodextrin or a α-cyclodextrin derivative;
n being chosen from 6 and 7 when A is β-cyclodextrin or a β-cyclodextrin derivative;
n being chosen from 6, 7 and 8 when A is γ-cyclodextrin or a γ-cyclodextrin derivative.

3. A pharmaceutical composition comprising, as active substance, a compound according to claim 2 , in association with a pharmaceutically acceptable vehicle.

4. The compound according to claim 2 , wherein the compound of formula (I) is selected from the group consisting of:
(i) a compound of formula (I) wherein Z is of formula (1″):

T representing O, S or CH 2 ;
(ii) a compound of formula (I) wherein X is of formula (1), wherein p equals 0 and Z is of formula (1″), corresponding to the following formula (2a):

wherein Y and q are as defined above, T representing O, S or CH 2 ;
(iii) a compound of formula (I) wherein X is of formula (1), wherein p equals 1 and Z is of formula (1″), corresponding to the following formula (2b):

wherein W, L, Y and q are as defined above, T representing O, S or CH 2 ;
(iv) a compound of formula (I) wherein X is of formula (1), wherein p equals 0, Y represents (1′) and Z is of formula (1″), corresponding to the following formula (2c):

wherein q is as defined in above, T representing O, S or CH 2 ;
(v) a compound of formula (I), wherein X is of formula (1), wherein p equals 1, L is of formula (1 1 ), and Z is of formula (1″), corresponding to the following formula (2d):

wherein W, L, Y, m and q are as defined above, T representing O, S or CH 2 ;
(vi) a compound of formula (I), wherein X is of formula (1), wherein p equals 1, W and Y are of formula (1′), and Z is of formula (1″), corresponding to the following formula (2e):

wherein L and q are as defined above, T representing O, S or CH 2 ; and
(vii) a compound of formula (I), wherein X is of formula (1), wherein p equals 1, W and Y are of formula (1′), and Z is of formula (1″), corresponding to the following formula (2f):

wherein m and q are as defined in above, T representing O, S or CH 2 .

5. The compound according to claim 2 , wherein the compound of formula (I) is selected from the group consisting of:
(i) a compound of formula (I), wherein A is a cyclodextrin, X is of formula (1), wherein Z is of formula (1″), corresponding to the following formula:

wherein p, n, W, L, Y and q are as defined above, T representing O, S or CH 2 ;
(ii) a compound of formula (I), wherein A is a cyclodextrinX is of formula (1), wherein p equals 0 and Z is of formula (1″), corresponding to the following formula (IIa):

wherein n, Y and q are as defined above, T representing O, S or CH 2 ;
(iii) a compound of formula (I), wherein A is a cyclodextrin, X is of formula (1), wherein p equals 1 and Z is of formula (1″), corresponding to the following formula (IIb):

Assignees

• Centre Nat Rech Scient
• Univ Nantes
• Univ Picardie
• Univ Lille 1 Sciences & Technologies
• Univ Dauvergne
• Inst Nat Sante Rech Med

Inventors

• Bouckaert Julie
• Gouin Sebastien
• Deniaud David
• Bilyy Rostyslav
• Dumych Tetiana
• Sivignon Adeline
• Darfeuille-Michaud Arlette

Classifications

• C07H19/06

  Pyrimidine radicals · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• C07H15/26 Primary

  Acyclic or carbocyclic radicals, substituted by hetero rings · CPC title

• A61K47/61

  the organic macromolecular compound being a polysaccharide or a derivative thereof · CPC title

• A61K39/385

  Haptens or antigens, bound to carriers · CPC title