Substituted 2-imidazolidinones and 2-imidazolones and their use in the treatment of cancer

Patent metadata

Field	Value
Publication number	US-9579306-B2
Application number	US-201615061439-A
Country	US
Kind code	B2
Filing date	Mar 4, 2016
Priority date	Aug 16, 2011
Publication date	Feb 28, 2017
Grant date	Feb 28, 2017

Abstract

Compounds of formula (I) wherein R 1 , R 4 , R 8 , X and Y as defined herein are provided as useful for the inhibition of certain types of cancer cells, amongst others, breast cancer cells, or for the manufacture of anti-cancer agents.

First claim

The invention claimed is:

1. A method of treating cancer by hindering or blocking cell cycle progression, said method comprising administering a therapeutically effective amount of a composition comprising at least one compound of formula (I):

wherein:
imidazo ring is saturated or unsaturated;
R 1 is an unsubstituted C 3-8 linear or branched alkyl;
X is O or NH when Y═SO 2 ; and X═SO 2 when Y is O or NH;
or X is —CH═CH— and Y is C═O;
or X is C═O, —S— or C═CH 2 ; and Y is absent;
R 4 and R 8 is each independently selected from the group consisting of: H, OH, halogen, unsubstituted C 1-6 alkyl and unsubstituted C 1-6 alkoxy;
R 5 , R 6 and R 7 is each independently selected from the group consisting of: H, OH, halogen, unsubstituted C 1-6 alkyl and unsubstituted C 1-6 alkoxy, provided that at least one of R 4 , R 5 , R 6 , R 7 or R 8 is not H;
or a pharmaceutically acceptable derivative or salt thereof;
in admixture with at least one pharmaceutically-acceptable excipient, to a patient suffering from said cancer, wherein the cancer is gastrointestinal cancer, lung cancer, ovarian cancer, prostate cancer, breast cancer, uterine cancer, or cervical cancer.

2. The method of claim 1 , comprising the compound of formula (I) wherein:
R 1 is n-propyl, n-butyl, isobutyl, n-pentyl, isopentyl, 2,2-dimethylbutyl or n-hexyl;
X is O or NH when Y═SO 2 ; and X═SO 2 when Y is O or NH;
or X is —CH═CH— and Y is C═O;
or X is C═O, —S— or C═CH 2 ; and Y is absent;
R 4 and R 8 is each independently selected from the group consisting of: H, OH, halogen, unsubstituted C 1-6 alkyl and unsubstituted C 1-6 alkoxy;
R 5 , R 6 and R 7 is each independently selected from the group consisting of: H, OH, halogen, unsubstituted C 1-6 alkyl and unsubstituted C 1-6 alkoxy, provided that at least one of R 4 , R 5 , R 6 , R 7 or R 8 is not H;

or a pharmaceutically acceptable derivative or salt thereof.

3. The method of claim 2 , comprising the compound of formula (Ia) wherein:

wherein:
R 1 is n-propyl, n-butyl, isobutyl, n-pentyl, isopentyl, 2,2-dimethylbutyl or n-hexyl;
X is O or NH when Y═SO 2 ; and X═SO 2 when Y is O or NH;
R 4 and R 8 is each independently selected from the group consisting of: H, OH, halogen, unsubstituted C 1-4 alkyl and unsubstituted C 1-6 alkoxy;
R 5 , R 6 and R 7 is each independently selected from the group consisting of: H, OH, halogen, unsubstituted C 1-4 alkyl and unsubstituted C 1-4 alkoxy, provided that at least one of R 4 , R 5 , R 6 , R 7 or R 8 is not H;

or a pharmaceutically acceptable derivative or salt thereof.

4. The method of claim 3 , comprising the compound of formula (Ia) wherein:
R 1 is n-propyl, n-butyl, isobutyl, n-pentyl, isopently or n-hexyl;
X═SO 2 when Y is O or NH;
R 4 and R 8 are H;
R 5 , R 6 and R 7 is each independently selected from the group consisting of: H, halogen and
unsubstituted C 1-3 alkoxy, provided that at least one of R 4 , R 5 , R 6 , R 7 or R 8 is not H;

or a pharmaceutically acceptable derivative or salt thereof.

5. The method of claim 1 , comprising the compound of formula (I)
wherein:
R 1 is n-propyl, n-butyl, isobutyl or n-pentyl; X is O or NH when Y═SO 2 ; and X═SO 2 when Y is O or NH; R 4 is H and R 8 is H; R 5 , R 6 and R 7 is each independently selected from the group consisting of: H, halo, and unsubstituted C 1-3 alkoxy, provided that at least one of R 5 , R 6 and R 7 is not H, or a pharmaceutically acceptable derivative or salt thereof.

6. The method of claim 1 , comprising the compound of formula (Ib):

wherein R 1 is n-propyl, n-butyl, isobutyl or n-pentyl; Y═O or NH; R 5 , R 6 and R 7 is each independently selected from the group consisting of: H, Cl, I, Br, F, and OMe, provided that at least one of R 5 , R 6 and R 7 is not H, or a pharmaceutically acceptable derivative or salt thereof.

7. The method of claim 6 , comprising the compound of formula (Ib) wherein R 1 is n-butyl, isobutyl or n-pentyl; Y═O or NH; R 5 , R 6 and R 7 is each independently selected from the group consisting of: H, Cl, I, Br, F, and OMe, provided that at least one of R 5 , R 6 and R 7 is not H, or a pharmaceutically acceptable derivative or salt thereof.

8. The method of claim 7 , wherein the compound of formula (Ib) is selected from the group consisting of:

9. The method of claim 8 , wherein the compound of formula (Ib) is selected from the group consisting of:

10. The method of claim 1 , wherein the cancer is selected from the group consisting of: gastrointestinal cancer and breast cancer.

11. The method of claim 10 , wherein the cancer is breast cancer.

Assignees

• UNIVERSITé LAVAL
• Univ Laval

Inventors

• C -Gaudreault René
• Fortin Sébastien

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/635

  having a heterocyclic ring, e.g. sulfadiazine · CPC title

• C07D233/32

  One oxygen atom · CPC title

• A61K31/4166 Primary

  having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin · CPC title

• C07D233/36

  with hydrocarbon radicals, substituted by nitrogen atoms, attached to ring nitrogen atoms · CPC title