Combretastatin analogs

Patent metadata

Field	Value
Publication number	US-10100029-B2
Application number	US-201715849150-A
Country	US
Kind code	B2
Filing date	Dec 20, 2017
Priority date	Apr 19, 2013
Publication date	Oct 16, 2018
Grant date	Oct 16, 2018

Abstract

The present invention relates novel heterocyclic analogs of combretastatin, their synthesis, and their use as anti-cancer compounds. In particular, compounds of Formula (I), Formula (II), and Formula (V) are provided.

First claim

What is claimed is:

1. A method of inhibiting tubulin polymerization in a subject, the method comprising administering to the subject a compound comprising Formula (V) in combination with at least one pharmaceutically acceptable excipient:

wherein:
G is chosen from

Q is a quinolinyl moiety;
R 1 , R 2 , R 3 , R 4 , R 7 , R 8 , R 9 , R 10 , and R 11 are independently chosen from hydrogen, hydrocarbyl, substituted hydrocarbyl, alkylalkylamino, amidine, amino, carboxyl, cyano, ester, halogen, hydroxyl, and nitro;
R 5 is hydrogen and R 6 is cyano;
X and Y are independently chosen from O, CR 12 , CR 12 R 13 , S, SR 14 , N, or NR 15 , with the proviso that when X is N and Y is S or when Y is N and X is S, at least one of R 7 , R 8 , R 9 , R 10 , and R 11 is not a hydrogen;
R 12 , R 13 , R 14 , and R 15 are independently chosen from hydrogen, hydrocarbyl, substituted hydrocarbyl, alkylalkylamino, amidine, amino, carboxyl, cyano, ester, halogen, hydroxyl, and nitro; and
are independently a single bond that is present or absent, with the proviso that both are not present at the same time;
wherein when G is Q, R 5 is chosen from hydrogen, hydrocarbyl, substituted hydrocarbyl, carboxyl, ester, and cyano and R 6 is chosen from hydrocarbyl, substituted hydrocarbyl, carboxyl, ester, and cyano, with the proviso that when R 6 is cyano, at least one of R 7 , R 8 , R 10 , and R 11 is not a hydrogen.

2. The method of claim 1 , wherein R 1 , R 4 , R 7 , and R 11 are hydrogen.

3. The method of claim 1 , wherein R 8 , R 9 , and R 10 are independently chosen from hydrogen, methoxy, ethoxy, benzyloxy, substituted benzyloxy, hydroxyl, and lower alkyl groups.

4. The method of claim 3 , wherein R 8 , R 9 , and R 10 are independently chosen from hydrogen, hydroxyl, and methoxy.

5. The method of claim 4 , wherein R 8 , R 9 , and R 10 are independently chosen from hydrogen and methoxy.

6. The method of claim 1 , wherein X is chosen from C or S.

7. The method of claim 1 , wherein Y is chosen from O, S, and NR 15 .

8. The method of claim 1 , wherein G is Q with the proviso that where R 6 is cyano, R 8 and R 9 are not each OCH 3 .

9. The method of claim 8 , wherein Q is chosen from 2-quinolinyl and 3-quinolinyl.

10. The method of claim 8 , wherein R 5 is hydrogen and R 6 is cyano.

11. The method of claim 8 , wherein R 7 , R 8 , R 9 , R 10 , R 11 are independently chosen from hydrogen and hydroxyl.

12. The method of claim 8 , wherein R 8 , R 9 , and R 10 are independently chosen from hydrogen and hydroxyl.

13. The method of claim 8 , wherein R 8 , R 9 , and R 10 are hydroxyl.

14. The method of claim 1 , wherein the compound of Formula (V) is selected from the group consisting of

Assignees

• Bioventures Llc

Inventors

• Penthala Narsimha Reddy
• Crooks Peter
• Sonar Vijayakumar

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07D307/79

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring · CPC title

• C07D215/14

  Radicals substituted by oxygen atoms · CPC title

• C07D307/80

  Radicals substituted by oxygen atoms · CPC title

• C07D209/18

  Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title