Neomycin based compounds, and pharmaceutical use thereof

Patent metadata

Field	Value
Publication number	US-12508275-B2
Application number	US-202017764221-A
Country	US
Kind code	B2
Filing date	Sep 30, 2020
Priority date	Sep 30, 2019
Publication date	Dec 30, 2025
Grant date	Dec 30, 2025

Abstract

The present invention relates to the field of medicine, in particular of oncology. Especially, it provides new compounds useful in the treatment of various cancers, such as glioblastoma, colorectal or breast cancers. The present disclosure also relates to pharmaceutical compositions containing the disclosed compounds.

First claim

The invention claimed is:

1 . A compound of general formula (I):

wherein X is selected in the group consisting of:

and wherein R is represented below:

with n being an integer from 1 to 6;
and R 1 being a —NHR 2 , —NR 3 R 4 , or a guanidyl group;
R 2 is a hydrogen atom, an amine protecting group, or an aminoalkyl group;
R 3 and R 4 , identical or different, are independently a hydrogen atom, an amine protecting group, or an aminoalkyl group;
where any amine group being optionally protected by any amine protecting group;
or a salt, stereoisomer, a racemic mixture, geometric isomers, or a mixture thereof.

2 . The compound according to claim 1 , wherein
X is

wherein R is represented below:

with n being an integer from 1 to 6 and R 1 is a guanidyl group, or R 1 is —NR 3 R 4 , with R 3 being an hydrogen atom or an amine protecting group, and R 4 being an aminoalkyl group.

3 . The compound according to claim 1 , wherein
X is

wherein R is represented below:

with n being an integer from 1 to 6 and R 1 is —NH 2 , or R 1 is —NR 3 R 4 , with R 3 being an hydrogen atom or an amine protecting group, and R 4 being an aminoalkyl group.

4 . The compound according to claim 1 , wherein
R 1 is a —NHR 2 , —NR 3 R 4 , or a guanidyl group; R 2 is a hydrogen atom, an amine protecting group, or —(CH 2 ) m NH 2 ; R 3 and R 4 , identical or different, are independently a hydrogen atom, an amine protecting group, or —(CH 2 ) m NH 2 ; where m is an integer from 1 to 6.

5 . The compound according to claim 4 , wherein m is 2, 3, 4, 5, or 6.

6 . The compound according to claim 1 , wherein at least one, or all, of the following definitions are met:
n is 3 or 4; R 1 is selected from the group consisting of —NH 2 , a guanidyl group, and —NH(CH 2 ) m NH 2 , where m is an integer from 1 to 6.

7 . The compound according to claim 1 , wherein R is one of the following formulas:

8 . The compound according to claim 1 , wherein said compound is selected from the group consisting of:

9 . The compound according to claim 1 , wherein the compound is:

10 . A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier and/or excipient.

11 . A method of treating a glioma, glioblastoma or epithelial tumor cancer with cancer stem cells, comprising administration of a compound according to claim 1 to a subject in need thereof.

12 . The method according to claim 11 , wherein the subject in need thereof has a glioma or a glioblastoma.

13 . The method according to claim 11 , wherein said compound is administered in combination with a chemotherapeutic agent or radiotherapy.

14 . The method according to claim 13 , wherein said subject has a glioblastoma and said compound is administered in combination with a chemotherapeutic agent.

15 . The method according to claim 14 , wherein the chemotherapeutic agent is temozolomide.

Assignees

• Univ Cote D'Azur
• Centre Nat Rech Scient
• Inst Nat Sante Rech Med
• Centre Hospitalier Univ De Nice

Inventors

• Virolle Thierry
• DUCA Maria
• Vo Duc Duy
• Turchi Laurent
• Chneiweiss Hervé
• Junier Marie-Pierre

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/53

  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

• A61K31/7056

  containing five-membered rings with nitrogen as a ring hetero atom · CPC title

• A61K31/7036 Primary

  having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins · CPC title

• C07H15/232 Primary

  with at least three saccharide radicals in the molecule, e.g. lividomycin, neomycin, paromomycin · CPC title