Disulfonate stilbenes for use in the treatment of proliferative diseases

Patent metadata

Field	Value
Publication number	US-2022016068-A1
Application number	US-201917295231-A
Country	US
Kind code	A1
Filing date	Nov 22, 2019
Priority date	Nov 22, 2018
Publication date	Jan 20, 2022
Grant date	—

Abstract

Compounds of general formula:wherein R0A and R0B are independently selected from hydrogen and pharmaceutically acceptable cations; and RA and RB are identical and selected from amide, carbamate, sulphonamide, azido, cyano and halide. Also, a pharmaceutical composition including one of the compounds. The composition may also include another active ingredient, especially an antineoplastic agent. Further a compound or a composition for use as a medicament, especially a compound or a composition for use in the treatment of a proliferative disease such as for example cancer.

First claim

1 - 15 . (canceled)

16 . A method of treatment of a proliferative disease in a subject in need thereof, wherein the method comprises a step of administration to the subject of a compound of Formula (I)

wherein:
R 0A and R 0B are independently selected from the group consisting of hydrogen, lithium, sodium, and potassium; and
R A and R B are identical and selected from the group consisting of —NH—COR, —NH—COOR, —NH—SO 2 R, azido, cyano, and halide;
wherein each R is independently selected from the group consisting of (C 1 -C 6 )-alkyl, (C 3 -C 6 )-cycloalkyl, (C 6 -C 10 )-aryl, and (C 6 -C 10 )-heteroaryl;
wherein the (C 1 -C 6 )-alkyl, (C 3 -C 6 )-cycloalkyl, (C 6 -C 10 )-aryl, or (C 6 -C 10 )-heteroaryl is optionally substituted by one or two substituent(s) independently selected from the group consisting of (C 1 -C 6 )-alkyl, (C 3 -C 6 )-cycloalkyl, (C 1 -C 6 )-alkoxy, (C 1 -C 6 )-alkyl-S—, and nitro;

or a pharmaceutically acceptable salt thereof.

17 . The method according to claim 16 , wherein each R is independently selected from the group consisting of (C 1 -C 4 )-alkyl, phenyl, pyridinyl, and diazinyl;
wherein the phenyl, pyridinyl, or diazinyl is optionally substituted by one or two substituent(s) independently selected from the group consisting of (C 1 -C 3 )-alkyl, (C 1 -C 3 )-alkoxy, and nitro.

18 . The method according to claim 17 , wherein the phenyl, pyridinyl, or diazinyl is substituted by one or two substituent(s) independently selected from the group consisting of methyl, methoxy, and nitro.

19 . The method according to claim 16 , wherein R A and R B are selected from —NH—COR, —NH—COOR, and —NH—SO 2 R, wherein each R is independently selected from the group consisting of (C 1 -C 6 )-alkyl, (C 3 -C 6 )-cycloalkyl, (C 6 -C 10 )-aryl, and (C 6 -C 10 )-heteroaryl; wherein the (C 1 -C 6 )-alkyl, (C 3 -C 6 )-cycloalkyl, (C 6 -C 10 )-aryl, and (C 6 -C 10 )-heteroaryl is optionally substituted by one or two substituent(s) independently selected from the group consisting of (C 1 -C 6 )-alkyl, (C 3 -C 6 )-cycloalkyl, (C 1 -C 6 )-alkoxy, (C 1 -C 6 )-alkyl-S—, and nitro.

20 . The method according to claim 16 , wherein R A and R B are selected from —NH—COR, —NH—COOR, and —NH—SO 2 R, wherein each R is independently selected from the group consisting of (C 1 -C 4 )-alkyl, phenyl, pyridinyl, and diazinyl; wherein the phenyl, pyridinyl, or diazinyl is optionally substituted by one or two substituent(s) independently selected from the group consisting of (C 1 -C 3 )-alkyl, (C 1 -C 3 )-alkoxy, and nitro.

21 . The method according to claim 16 , wherein R A and R B are selected from azido, cyano, and halide.

22 . The method according to claim 16 , wherein the halide is iodine.

23 . The method according to claim 16 , wherein both R 0A and R 0B are sodium or wherein both R 0A and R 0B are potassium.

24 . The method according to claim 16 , wherein the compound of Formula (I) is selected from:

and pharmaceutically acceptable salts thereof.

25 . The method according to claim 16 , wherein said proliferative disease is a cancer.

26 . The method according to claim 16 , wherein said proliferative disease is breast cancer, glioblastoma, or multiple myeloma.

27 . The method according to claim 16 , comprising a step of administration to the subject of a composition, wherein the composition comprises the compound of Formula (I) and a pharmaceutically acceptable excipient.

28 . The method according to claim 27 , wherein the composition further comprises at least another active ingredient.

29 . The method according to claim 28 , wherein the at least another active ingredient is an antineoplastic active ingredient.

30 . A compound of Formula (II)

wherein:
R 0A and R 0B are independently selected from the group consisting of hydrogen, lithium, sodium, and potassium; and
each R is independently selected from the group consisting of (C 6 -C 10 )-aryl and (C 6 -C 10 )-heteroaryl;

or a pharmaceutically acceptable salt thereof.

31 . The compound according to claim 30 , wherein each R is independently selected from phenyl, pyridinyl, and diazinyl.

32 . The compound according to claim 31 , wherein each R is phenyl.

33 . The compound according to claim 30 , wherein R 0A and R 0B are identical.

34 . The compound according to claim 33 , wherein both R 0A and R 0B are sodium.

35 . A process for manufacturing a compound according to claim 30 , comprising a step of reaction of (E)-6,6′-(ethene-1,2-diyl)bis(3-aminobenzenesulfonate) with an halo-formate.

Assignees

• Univ Nantes
• Centre Nat Rech Scient
• Univ Du Mans

Inventors

• Fleury Fabrice
• Demeyer Alexandre
• Weigel Pierre
• Chenais Benoit
• Mathé Monique
• Lebreton Jacques

Classifications

• A61K31/27 Primary

  of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine · CPC title

• A61K31/18

  Sulfonamides (compounds containing a para-N-benzene-sulfonyl-N- group A61K31/63) · CPC title

• A61K31/167

  having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol · CPC title

• A61K31/166

  having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol · CPC title

• A61K45/06

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