Compositions and methods for treating diseases and conditions

Patent metadata

Field	Value
Publication number	US-11072606-B2
Application number	US-201916600248-A
Country	US
Kind code	B2
Filing date	Oct 11, 2019
Priority date	Dec 10, 2014
Publication date	Jul 27, 2021
Grant date	Jul 27, 2021

Abstract

A compound of Formula II, or a salt, ester, solvate, hydrate or prodrug thereof:where:X1 is a branched or unbranched C1-10 alkyl, (CH2)s—NH—(CH2)t, (CH2)s—O—(CH2)t, or (CH2)s—C(NH2)—(CH2)v—NH—(CH2)t, where s, t and v are each, independently an integer from 1 to 5;A and B are each, independently, C6-10aryl, C6-10aryl-C1-6alkyl, C3-9 heteroaryl, or C3-9heteroaryl-C1-6alkyl, each optionally substituted with 1, 2 or 3 independently selected Rg groups;C and D are each, independently, C3-7 cycloalkyl, C3-7 cycloalkyl-C1-6alkyl, C3-7 heterocycloalkyl, C3-7 heterocycloalkyl-C1-6 alkyl, C6-10aryl, C6-10aryl-C1-6alkyl, C3-9 heteroaryl, or C3-9heteroaryl-C1-6alkyl, each optionally substituted with 1, 2 or 3 independently selected Rg groups;each Rg is, independently, halogen, C1-6 alkyl, C1-6 haloalkyl, hydroxyl, C1-6 alkoxy, C1-6 haloalkoxy, amino, C1-6alkylamino, or di-C1-6alkylamino; andn1 and p1 are each, independently, integers from 1 to 10.

First claim

What is claimed is:

1. A method for treating an inflammatory disorder, comprising administering to a subject in need thereof a compound, wherein the compound is:

wherein X 1 is a branched or unbranched C 1-10 alkyl, (CH 2 ) s —NH—(CH 2 ) t , (CH 2 ) s —O—(CH 2 ) t , or (CH 2 ) s —CH(NH 2 )—(CH 2 ) v —NH—(CH 2 ) t ,where s, t and v are each, independently, an integer from 1 to 5;
n 1 and p 1 are each, independently, integers from 1 to 10; and
R 20 -R 33 are each independently hydrogen, halogen, or C 1-6 haloalkyl, provided at least one of R 20 -R 33 is a halogen; and
wherein the inflammatory disorder is selected from asthma, chronic obstructive lung disease, pulmonary fibrosis, pneumonitis, pneumonia, cystic fibrosis, psoriasis, arthritis/rheumatoid arthritis, rhinitis, pharyngitis, cystitis, prostatitis, dermatitis, allergy, nephritis, conjunctivitis, encephalitis, meningitis, opthalmitis, uveitis, pleuritis, pericarditis, myocarditis, atherosclerosis, human immunodeficiency virus related inflammation, diabetes, osteoarthritis, psoriatic arthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, sepsis, vasculitis, bursitis, connective tissue disease, autoimmune diseases, viral or influenza-induced inflammation, or edema.

2. The method of claim 1 , wherein the compound is:

3. The method of claim 1 , wherein R 21 and R 23 are fluorine.

4. The method of claim 1 , wherein R 25 and R 30 are fluorine.

5. The method of claim 1 , wherein X 1 is a branched or unbranched C 1-10 alkyl.

6. The method of claim 1 , wherein R 26 and R 29 are fluorine.

7. The method of claim 1 , wherein R 21 and R 32 are each fluorine.

8. The method of claim 1 , wherein X 1 is —CH 2 CH 2 —.

9. The method of claim 1 , wherein the inflammatory disorder is inflammatory bowel disease.

10. The method of claim 1 , wherein the inflammatory disorder is Crohn's disease.

11. The method of claim 1 , wherein the inflammatory disorder is colitis.

12. The method of claim 8 , wherein the inflammatory disorder is inflammatory bowel disease.

13. The method of claim 8 , wherein the inflammatory disorder is Crohn's disease.

14. The method of claim 8 , wherein the inflammatory disorder is colitis.

15. The method of claim 1 , wherein the inflammatory disorder is at least one of hayfever, lupus erythematosis (SLE), polymyalgia rheumatica, scleroderma, Wegener's granulomatosis, temporal arteritis, vasculitis, cryoglobulinemia, and multiple sclerosis.

16. A method for diminishing supraphysiological levels of at least one of TNFα, IL-β, or IL-6 in a subject in need thereof, comprising administering to the subject an effective amount of a compound, wherein the compound is:

wherein X 1 is a branched or unbranched C 1-10 alkyl, (CH 2 ) s —NH—(CH 2 ) t , (CH 2 ) s —O—(CH 2 ) t , or (CH 2 ) s —CH(NH 2 )—(CH 2 ) v —NH—(CH 2 ) t , where s, t and v are each, independently, an integer from 1 to 5;

n 1 and p 1 are each, independently, integers from 1 to 10; and
R 20 -R 33 are each independently hydrogen, halogen, or C 1-6 haloalkyl, provided at least one of R 20 -R 33 is a halogen.

17. The method of claim 16 , wherein the compound is:

18. The method of claim 16 , wherein R 21 and R 23 are fluorine.

19. The method of claim 16 , wherein R 25 and R 30 are fluorine.

20. The method of claim 16 , wherein X 1 is a branched or unbranched C 1-10 alkyl.

21. The method of claim 16 , wherein R 26 and R 29 are fluorine.

22. The method of claim 16 , wherein R 21 and R 32 are each fluorine.

23. The method of claim 16 , wherein X 1 is —CH 2 CH 2 —.

Assignees

• Univ Of Pittsburgh—Of The Commonwealth System Of Higher Education
• Us Gov Veterans Affairs

Inventors

• Chen Beibei
• Mallampalli Rama K

Classifications

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• A61P13/02

  of urine or of the urinary tract, e.g. urine acidifiers · CPC title

• C07D239/30

  Halogen atoms or nitro radicals · CPC title

• A61K31/506

  not condensed and containing further heterocyclic rings · CPC title

• A61P1/00

  Drugs for disorders of the alimentary tract or the digestive system · CPC title