Bronchodilators for treating obstructive lung disease

Patent metadata

Field	Value
Publication number	US-12257248-B2
Application number	US-202117464233-A
Country	US
Kind code	B2
Filing date	Sep 1, 2021
Priority date	Sep 1, 2020
Publication date	Mar 25, 2025
Grant date	Mar 25, 2025

Abstract

Disclosed herein are compounds useful for treating obstructive lung diseases. The compounds are TAS2Rs agonists and may further be used to treat disorders and conditions implicated by TAS2R. In some instances the disclosed compounds can be used to treat asthma.

First claim

What is claimed is:

1. A method for treating an obstructive lung disease in a patient in need thereof, comprising administering to the patient a compound having the formula:

or a pharmaceutically acceptable salt thereof, wherein
Z 1 is O, S, or NR a ; wherein R a is H, C 1-8 alkyl, or C 1-8 alkoxy;
Z 2 is O, S, or NR b ; wherein R b is H, C 1-8 alkyl, or C 1-8 alkoxy;
R 1 is selected from R a , OR a , N(R a ) 2 , F, Cl, Br, I, NO 2 , CN, wherein R a is in each case selected from H, C 1-8 alkyl, C 2-8 alkenyl; C 2-8 alkynyl;
R 2 is selected from R b , OR b , N(R b ) 2 , F, Cl, Br, I, NO 2 , CN, wherein R b is in each case selected from H, C 1-8 alkyl, C 2-8 alkenyl; C 2-8 alkynyl;
R 3 is selected from R c , OR c , N(R c ) 2 , F, Cl, Br, I, NO 2 , CN, wherein R c is in each case selected from H, C 1-8 alkyl, C 2-8 alkenyl; C 2-8 alkynyl;
wherein any two or more of R 1 , R 2 , and R 3 may together form a ring; and
X 2 is N;
R 6 is selected from R d , OR d , N(R d ) 2 , F, Cl, Br, I, NO 2 , CN, wherein R d is in each case selected from H, C 1-8 alkyl, C 2-8 alkenyl; C 2-8 alkynyl;
R 7 is selected from R e , OR e , N(R e ) 2 , F, Cl, Br, I, NO 2 , CN, wherein R e is in each case selected from H, C 1-8 alkyl, C 2-8 alkenyl; C 2-8 alkynyl;
R 8 is selected from R f , OR f , N(R f ) 2 , F, Cl, Br, I, NO 2 , CN, wherein R f is in each case selected from H, C 1-8 alkyl, C 2-8 alkenyl; C 2-8 alkynyl;
wherein any two or more of R 6 , R 7 , and R 8 may together form a ring; and
wherein R 8 may form a ring with R b ,
wherein the obstructive lung disease is asthma, chronic obstructive pulmonary disease, emphysema, bronchitis, cystic fibrosis, bronchiectasis, bronchiolitis, or allergic bronchopulmonary aspergillosis.

2. The method according to claim 1 , wherein Z 1 and Z 2 are both O.

3. The method according to claim 1 , wherein R 3 and R 8 are each H.

4. The method according to claim 1 , wherein R 2 and R 7 are each H.

5. The method according to claim 1 , wherein R 1 and R 6 are each H.

6. The method according to claim 1 , wherein R 1 , R 2 , R 3 , R 6 , R 7 , and R 8 are each H.

7. The method according to claim 2 , wherein R 1 , R 2 , R 3 , R 6 , R 7 , and R 8 are each H.

8. The method according to claim 1 , wherein the obstructive lung disease is asthma.

9. The method according to claim 1 , wherein the obstructive lung disease is chronic obstructive pulmonary disease.

10. The method according to claim 1 , wherein the obstructive lung disease is emphysema.

11. The method according to claim 1 , wherein the obstructive lung disease is bronchitis.

12. The method according to claim 1 , wherein the obstructive lung disease is cystic fibrosis.

13. The method according to claim 1 , wherein the obstructive lung disease is bronchiectasis.

14. The method according to claim 1 , wherein the obstructive lung disease is bronchiolitis.

15. The method according to claim 1 , wherein the obstructive lung disease is allergic bronchopulmonary aspergillosis.

16. The method according to claim 1 , wherein the compound is administered by inhalation.

Assignees

• Univ South Florida
• Univ Rutgers

Inventors

• Liggett Stephen
• Leahy James
• Kim Donghwa
• An Steven

Classifications

• A61K31/444

  containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone · CPC title

• A61K31/122

  having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin · CPC title

• A61K31/4745 Primary

  condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48) · CPC title