Indole compounds for use in treating inflammation and cancer

Patent metadata

Field	Value
Publication number	US-9597316-B2
Application number	US-201314651113-A
Country	US
Kind code	B2
Filing date	Dec 26, 2013
Priority date	Dec 28, 2012
Publication date	Mar 21, 2017
Grant date	Mar 21, 2017

Abstract

Provided herein are compounds, comprising Formula (I) or Formula (II), and their pharmaceutically acceptable salts. Also provided are pharmaceutical compositions comprising a pharmaceutically acceptable excipient and at least one compound of Formula (I) and (II), singly or in combination with other pharmaceutically active ingredients, such as anti-inflammatory agents or anticancer agents. These compounds and pharmaceutical compositions are useful for treating inflammation or an inflammation related disorder in a subject via administration to the subject. These compounds and pharmaceutical compositions are also useful for inhibiting COX-2, for treating cancer, for reducing the size of a neoplasm, and for inhibiting tubulin polymerization in a cell.

First claim

What is claimed is:

1. A compound comprising Formula (I) or a pharmaceutically acceptable salt thereof:

wherein:
R 1 is chosen from hydrogen, halogen, hydrocarbyl, and substituted hydrocarbyl;
R 2 is chosen from hydrocarbyl and substituted hydrocarbyl;
X 1 is chosen from hydrocarbyl, substituted hydrocarbyl, nitrogen, oxygen, and sulfur;
X 2 is chosen from hydrocarbyl, substituted hydrocarbyl, nitrogen, oxygen, and sulfur; and
n is an integer from 0 to 10.

2. The compound of claim 1 , wherein n is 0, 1, or 2.

3. The compound of claim 1 , wherein one of X 1 and X 2 is nitrogen.

4. The compound of claim 1 , wherein X 1 and X 2 are both nitrogen.

5. The compound of claim 1 , wherein R 1 is hydrogen.

6. The compound of claim 1 , wherein R 1 is halogen.

7. The compound of claim 6 , wherein R 1 is bromo or chloro.

8. The compound of claim 1 , wherein R 1 is OCH 3 .

9. The compound of claim 1 , wherein R 2 is hydrocarbyl selected from the group consisting of phenyl, 1-naphthyl, and 2-naphthyl.

10. The compound of claim 1 , wherein R 2 is substituted hydrocarbyl selected from the group consisting of 4-F—C 6 H 4 , 4-OCH 3 —C 6 H 4 , 4-CN—C 6 H 4 , 4-COOCH 3 —C 6 H 4 , and 2-Br—C 6 H 4 .

11. A compound comprising Formula (II) or a pharmaceutically acceptable salt thereof:

wherein:
R 1 is chosen from hydrogen, halogen, hydrocarbyl, and substituted hydrocarbyl;
R 2 is chosen from hydrocarbyl, and substituted hydrocarbyl; and
n is an integer from 0 to 10.

12. The compound of claim 11 , wherein R 1 is hydrogen.

13. The compound of claim 11 , wherein R 1 is halogen.

14. The compound of claim 13 , wherein R 1 is bromo or chloro.

15. The compound of claim 11 , wherein R 1 is OCH 3 .

16. The compound of claim 11 , wherein R 2 is hydrocarbyl selected from the group consisting of phenyl, 1-naphthyl, and 2-naphthyl.

17. The compound of claim 11 , wherein R 2 is substituted hydrocarbyl selected from the group consisting of 4-F—C 6 H 4 , 4-OCH 3 —C 6 H 4 , 4-CN—C 6 H 4 , 4-COOCH 3 —C 6 H 4 , and 2-Br—C 6 H 4 .

18. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 1 .

19. A combination comprising an anti-inflammatory agent and/or a chemotherapeutic agent, and a compound of claim 1 .

20. A method for treating inflammation, treating an inflammation related disorder, inhibiting COX-2, treating cancer, reducing the size of a neoplasm, or inhibiting tubulin polymerization in a cell of a subject in need thereof, the method comprising administering to the subject a compound of claim 1 .

Assignees

• Penthala Narsimha Reddy
• Crooks Peter
• Bioventures Llc

Inventors

• Penthala Narsimha Reddy
• Crooks Peter

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61K31/515

  Barbituric acids; Derivatives thereof, e.g. sodium pentobarbital · CPC title

• A61K31/404 Primary

  Indoles, e.g. pindolol · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title