Small molecules that bind MR1

Patent metadata

Field	Value
Publication number	US-10457682-B2
Application number	US-201715789955-A
Country	US
Kind code	B2
Filing date	Oct 20, 2017
Priority date	Oct 21, 2016
Publication date	Oct 29, 2019
Grant date	Oct 29, 2019

Abstract

Disclosed are small molecules and pharmaceutical compositions comprising them that can be used in treating diseases associated with the major histocompatibility complex (MHC) molecule MR1.

First claim

The invention claimed is:

1. A method of treating a respiratory infection of Mycobacterium tuberculosis or Streptococcus pyogenes in a human subject, the method comprising administering to the human subject in need thereof a pharmaceutically effective amount of a compound selected from Formula 1b, Formula 2b, and Formula 3b, or a pharmaceutically acceptable salt thereof:

wherein, in each appearance:
R 1 is independently selected from H, OH, C 1 -C 3 alkyl, and —CH═O;
R 2 is independently selected from H, a 5-10-membered carbocycle, a 5-10-membered heterocycle, and
C 1 -C 3 alkyl, wherein the C 1 -C 3 alkyl can be substituted by 1 or 2 substituents selected from OH and CO 2 H;
R 3 is selected from OH and —O(C═O)—C 1 -C 3 alkyl;
R 4 is independently selected from H, OH, C 1 -C 3 alkyl, and —CH═O;
R 5 is independently selected from H, a 5-10-membered carbocycle, a 5-10-membered heterocycle, and
C 1 -C 3 alkyl, wherein the C 1 -C 3 alkyl can be substituted by 1 or 2 substituents selected from OH and CO 2 H;
R 6 is selected from OH and —O(C═O)-C 1 -C 3 alkyl; and
R 7 is H or OH.

2. The method of claim 1 , wherein the compound is of Formula 1b, or a pharmaceutically acceptable salt thereof:

wherein R 1 is independently selected from H, OH, C 1 -C 3 alkyl, and —CH═O;
R 2 is independently selected from H, a 5-10-membered carbocycle, a 5-10-membered heterocycle, and C 1 -C 3 alkyl, wherein the C 1 -C 3 alkyl can be substituted by 1 or 2 substituents selected from OH and CO 2 H; and
R 3 is selected from OH and —O(C═O)-C 1 -C 3 alkyl.

3. The method of claim 1 , wherein the compound is selected from the group of:

or a pharmaceutically acceptable salt thereof.

4. The method of claim 1 , wherein the compound is of Formula 3b, or a pharmaceutically acceptable salt thereof:

wherein R 4 is independently selected from H, OH, C 1 -C 3 alkyl, and —CH═O;
R 5 is independently selected from H, a 5-10-membered carbocycle, a 5-10-membered heterocycle, and C 1 -C 3 alkyl, wherein the C 1 -C 3 alkyl can be substituted by 1 or 2 substituents selected from OH and CO 2 H;
R 6 is selected from OH and —O(C═O)-C 1 -C 3 alkyl; and
R 7 is H or OH.

5. The method of claim 1 , wherein the compound is selected from the group of:

or a pharmaceutically acceptable salt thereof.

6. The method of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.

7. The method of claim 1 , wherein the compound is:
or a pharmaceutically acceptable salt thereof.

Assignees

• Univ Oregon Health & Science
• Us Veterans Affairs

Inventors

• Lewinsohn David
• Harriff Melanie
• Nilsen Aaron
• Jin Haihong
• Adams Erin
• Froyd Cara
• Mcmurtrey Curtis
• Hildebrand William

Classifications

• C07D475/14 Primary

  Benz [g] pteridines, e.g. riboflavin · CPC title

• C07D475/02

  with an oxygen atom directly attached in position 4 · CPC title

• A61P31/06

  for tuberculosis · CPC title