Biguanide derivatives and their rearrangement products for use in the treatment of cancer

Patent metadata

Field	Value
Publication number	US-11440906-B2
Application number	US-201816956003-A
Country	US
Kind code	B2
Filing date	Dec 21, 2018
Priority date	Dec 22, 2017
Publication date	Sep 13, 2022
Grant date	Sep 13, 2022

Abstract

The present disclosure relates to biguanide derivatives of formula (I) and their rearrangement products. The present disclosure also relates to the use of these compounds in a method for treating cancer, in particular melanoma.

First claim

The invention claimed is:

1. A compound of formula (II) or (III)

wherein
Y′ is —SR 4 or —OR 5 ,
R 4 is selected from C 1 -C 6 alkyl and protecting groups selected from any group linked by a disulfide function, thioesters, alkyl, alkenyl and alkynyl thioethers, benzyl thioethers, alkylarylmethyl thioethers, and triarylmethylthioethers;
R 5 is selected from protecting groups selected from esters, silylated ethers, alkoxymethyl ethers, benzyl ethers tetrahydropyranyl ethers, pentoses, and hexoses;
each R′ is independently selected from halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, —OH, —NR″R′″, —NO 2 , —CN and —(CO)—R;
n is 0 to 4;
R 3 is selected from C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, heterocyclyl having 5 to 10 ring atoms, aryl having 6 to 10 ring atoms, heteroaryl having 5 to 10 ring atoms and C 7 -C 16 aralkyl, said alkyl, cycloalkyl, haloalkyl, alkenyl, alkynyl, heterocyclyl, aryl, heteroaryl and aralkyl being optionally substituted with one or more substituents independently selected from halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, —OH, —NR″R″, —NO 2 , —CN and —(CO)—R;
each R is independently selected from H, C 1 -C 6 alkyl, C 1 -C 6 alkoxy and —NR″R″ ‘;
each R″ and R’ is independently selected from H and C 1 -C 6 alkyl.

2. The compound of claim 1 , wherein
Y′ is —SR 4 , R 4 being selected from C 1 -C 6 alkyl;
each R′ is independently selected from halogen and C 1 -C 6 alkoxy;
n is 0 to 1;
R 3 is selected from C 1 -C 6 haloalkyl, aryl having 6 to 10 ring atoms, heteroaryl having 5 to 10 ring atoms, and C 7 -C 16 aralkyl, said aryl, heteroaryl and aralkyl being optionally substituted with one or more substituents independently selected from halogen, C 1 -C 6 alkoxy, and —CN.

3. The compound of claim 1 , wherein the compound is

4. The compound of claim 1 , wherein the compound is selected from

5. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable carrier.

Assignees

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

Inventors

• Benhida Rachid
• Rocchi Stephane
• Ronco Cyril
• Jaune Emile
• Grytsai Oleksandr
• Tekaya Nedra

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07D417/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D409/14 Primary

  containing three or more hetero rings · CPC title

• C07D277/48

  by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof, e.g. carbonylguanidines · CPC title

• C07D277/82 Primary

  Nitrogen atoms · CPC title