Compositions and methods for treatment of inflammatory disorders

• US 10,668,092 B2
• Filed: 06/01/2018
• Issued: 06/02/2020
• Est. Priority Date: 09/24/2010
• Status: Active Grant

• Current Assignee: Johns Hopkins University, University of Pittsburgh of The Commonwealth System of Higher Education
• Original Assignee: Johns Hopkins University
• Inventors: Hackam, David, Sodhi, Chhinder P., Wipf, Peter
• Primary Examiner(s): Lewis, Patrick T
• Application Number:
  US15/996,383
• Publication Number:
  US 20180280418A1
• Time in Patent Office: 732 Days
• Field of Search: None
• CPC Class Codes: A61K 31/7008 Compounds having an amino group directly attached to a carbon atom of the saccharide radical, e.g. D-galactosamine, ranimustine
• CPC Class Codes: A61K 31/7024 Esters of saccharides
• CPC Class Codes: A61K 31/7028 Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
• CPC Class Codes: A61K 31/7034 attached to a carbocyclic compound, e.g. phloridzin

Abstract

The present invention relates to methods of treating infectious, inflammatory and post-traumatic disorders by administering various compounds newly discovered to have TLR4 inhibitory activity. In addition to methods of treatment, the present invention further provides for pharmaceutical compositions comprising said compounds, together with a suitable pharmaceutical carrier.

Claims

1. A compound having the following formula:

3. The compound of claim 1 having the formula:

8. A method for treatment of an inflammatory disease in a mammal in need thereof comprising administering to the mammal an effective amount of the compound of claim 1.

2. A compound having the following formula:

12. A method for treating an infectious or inflammatory disorder in a subject in need thereof comprising administering to the subject an effective amount of a compound of claim 2.

13. A method for treating an intestinal inflammatory disorder in a subject in need thereof comprising administering to the subject an effective amount of a compound of claim 2.

14. A method for treating an cardiovascular inflammatory disorder in a subject in need thereof comprising administering to the subject an effective amount of a compound of claim 2.

15. A method for treating an pulmonary inflammatory disorder in a subject in need thereof comprising administering to the subject an effective amount of a compound of claim 2.

16. A method for treating an traumatic injury in a subject in need thereof comprising administering to the subject an effective amount of a compound of claim 2.

4. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (II):

following formula;

6. The pharmaceutical composition of claim 4, further comprising an effective amount of at least one additional biologically active agent.

7. The pharmaceutical composition of claim 6, wherein the least one additional biologically active agent is an anti-inflammatory agent.

9. A method for treatment of an inflammatory disease in a mammal in need thereof comprising administering to the mammal and effective amount of the pharmaceutical composition of claim 4.

10. A method for treatment of necrotizing enterocolitis in the intestine of a mammal in need thereof comprising administering to the mammal and effective amount of the pharmaceutical composition claim 4.

11. A method for treatment of for treatment of pulmonary inflammation in a mammal in need thereof comprising administering to the mammal and effective amount of the pharmaceutical composition claim 4.

5. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (III):

17. A method for treating an infectious or inflammatory disorder in a subject in need thereof comprising administering to the subject an effective amount of a pharmaceutical composition of claim 5.

18. A method for treating an intestinal inflammatory disorder in a subject in need thereof comprising administering to the subject an effective amount of pharmaceutical composition of claim 5.

19. A method for treating an cardiovascular inflammatory disorder in a subject in need thereof comprising administering to the subject an effective amount of a pharmaceutical composition of claim 5.

20. A method for treating an pulmonary inflammatory disorder in a subject in need thereof comprising administering to the subject an effective amount of a pharmaceutical composition of claim 5.

21. A method for treating an traumatic injury in a subject in need thereof comprising administering to the subject an effective amount of a pharmaceutical composition of claim 5.