MAO-B selective inhibitor compounds, pharmaceutical compositions thereof and uses thereof

Patent metadata

Field	Value
Publication number	US-10196345-B2
Application number	US-201414915474-A
Country	US
Kind code	B2
Filing date	Aug 29, 2014
Priority date	Aug 30, 2013
Publication date	Feb 5, 2019
Grant date	Feb 5, 2019

Abstract

Described herein are a series of compounds having the structure of Formula I:

for use in the inhibition of MAO and uses thereof for the treatment of a barrier disease, obesity, solid epithelial cell tumor metastasis, diabetes, an auto-immune and inflammatory disease or a cardiometabolic disorder.

First claim

What is claimed is:

1. A compound of Formula II:

wherein:
A 1 is selected from H, F, Cl, Br, I, CN, OMe, NO 2 , and CO 2 H;
A 2 is selected from H, F, Cl, Br, I, CN, OMe, NO 2 , and CO 2 H;
E 1 is

and E 2 is H; or
E 1 and E 2 form a ring having the structure

wherein:

D is H, Me, CH 2 Cl, CH 2 F, CH 2 Br, CH 2 I, CH 2 CN, CH 2 CH 2 OH, CH 2 OCH 2- phenyl, CH 2 OH, or CO 2 Me; and
G is CH 2 N(Me)CH 2 CO 2 H.

2. The compound of claim 1 , wherein
A 1 is selected from H, F, Cl, Br, CN, OMe, NO 2 , and CO 2 H;
A 2 is selected from H, F, Cl, Br, CN, OMe, NO 2 , and CO 2 H; and
D is H, Me, CH 2 Cl, CH 2 CN, CH 2 CH 2 OH, CH 2 OCH 2- phenyl, CH 2 OH, or CO 2 Me.

3. The compound of claim 1 , wherein
A 1 is selected from H, F, Cl, Br, CN, OMe, NO 2 , and CO 2 H;
A 2 is selected from H, F, Cl, Br, CN, OMe, NO 2 , and CO 2 H; and
D is Me, CH 2 Cl, CH 2 CN, CH 2 CH 2 OH, CH 2 OCH 2- phenyl, CH 2 OH, or CO 2 Me.

4. The compound of claim 1 , wherein
A 1 is selected from H, F, Cl, Br, OMe, and NO 2 ;
A 2 is selected from H, F, Cl, Br, OMe, and NO 2 ; and
D is Me, CH 2 Cl, CH 2 CN, CH 2 OH, or CO 2 Me.

5. The compound of claim 1 , wherein
A 1 is H, F, Cl, Br or OMe;
A 2 is from H, F, Cl, Br or OMe; and
D is Me, CH 2 Cl or CH 2 OH.

6. The compound of claim 1 , wherein the compound is selected from:

7. The compound of claim 1 , wherein the compound is selected from:

8. The compound of claim 1 , wherein the compound is selected from:

9. The compound of claim 1 , wherein the compound is

10. A method of treating ulcerative colitis, Crohn's disease, periodontitis, obesity, septicemia, diarrheal disease caused by a pathogenic bacterium, or rheumatoid arthritis, the method comprising administering an MAO-B selective inhibitor of claim 1 to a subject in need thereof.

11. The method of claim 10 , wherein the disease is septicemia, Crohn's disease, ulcerative colitis, periodontitis, diarrheal disease caused by a pathogenic bacterium, or asthma.

12. The method of claim 10 , wherein the disease is obesity.

13. The method of claim 10 , wherein the disease is rheumatoid arthritis.

14. A method of treating ulcerative colitis, Crohn's disease, periodontitis, obesity, septicemia, diarrheal disease caused by a pathogenic bacterium or rheumatoid arthritis, the method comprising administering an MAO-B selective inhibitor having a reduced ability to cross the blood brain barrier to a subject in need thereof wherein the MAO-B selective inhibitor having a reduced ability to cross the blood brain barrier is a compound of claim 1 .

15. A commercial package comprising: (a) a compound of claim 1 ; and (b) instructions for use of the compound in the treatment of ulcerative colitis, Crohn's disease, periodontitis, obesity, septicemia, diarrheal disease caused by a pathogenic bacterium or rheumatoid arthritis.

16. A pharmaceutical composition, the composition comprising: (a) a compound of claim 1 ; and (b) a pharmaceutically acceptable carrier.

Assignees

• Univ British Columbia
• Centre For Drug Res And Development

Inventors

• Putnins Edward Ewald
• Grierson David Scott
• Gealageas Ronan F B
• Devineau Alice Andree Valentine
• Dullaghan Edith Mary

Classifications

• A61P43/00

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

• A61P37/02

  Immunomodulators · CPC title

• A61P35/04

  specific for metastasis · CPC title

• A61P9/12

  Antihypertensives · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title