Granted Patent B2

US 12,213,973 · App. 18/047,497 · Granted Feb 4, 2025

Inventors: Richard Bruce Silverman (Evanston, IL); Pathum Manjula Weerawarna (Evanston, IL)

Assignee: Northwestern University

A61K31/4709A61K45/06A61P31/04C07D401/12

Abstract

Claims (39)

1. A compound of a Formula I(a) or I(b), or a salt thereof:

wherein if the compound has the formula I(a), then:

(i) X is CH 2 or O;

L is aza-substituted alkylene of a formula —(CH 2 ) m NH(CH 2 ) n —, m and n being an integer independently selected from 0 to 4; and

R is an optionally substituted pyridyl or an amino; or

(ii) X is CH 2 or O;

L is alkylene; and

R is an optionally substituted pyridyl; and

wherein if the compound has the formula I(b), then:

X is O;

L is aza-substituted alkylene; and

R is pyridyl substituted with amino.

2. The compound of claim 1 , or a salt thereof, having the Formula I(a), wherein

X is CH 2 or O;

L is aza-substituted alkylene of a formula —(CH 2 ) m NH(CH 2 ) n —, m and n being an integer independently selected from 0 to 4; and

R is an optionally substituted pyridyl or an amino.

3. The compound of claim 1 , or a salt thereof, having the Formula I(a), wherein

X is CH 2 or O;

L is alkylene; and

R is an optionally substituted pyridyl.

4. The compound of claim 1 , or a salt thereof, having a Formula I(aa):

wherein m=0, n is an integer selected from 1 to 4; and

R 1 is hydrogen or amino.

5. The compound of claim 1 , wherein X is CH 2 , L is CH 2 , and R is an amino-substituted pyridyl.

6. The compound of claim 1 , wherein X is O, L is —(CH 2 ) 2 NHCH 2 —, and R is an amino-substituted pyridyl.

7. The compound of claim 1 , wherein X is CH 2 , L is a covalent bond, and R is an amino.

8. The compound of claim 2 selected from the group consisting of:

9. The compound of claim 1 , or a salt thereof, having the Formula I(b).

10. The compound of claim 3 , wherein the compound is

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

12. A pharmaceutical composition comprising an effective amount of the compound of claim 1 and at least one of a carrier, excipient, or diluent.

13. The pharmaceutical composition of claim 12 further comprising one or more antibiotics.

14. A method of treating a subject having a disease or disorder and in need of treatment, the method comprising administering to the subject the pharmaceutical composition of claim 12 , wherein the subject has or is at risk of developing a disease or disorder that is associated with bacterial nitric oxide synthase activity.

15. The method of claim 14 , wherein the pharmaceutical composition further comprises one or more antibiotics.

16. The method of claim 14 further comprising administering an antibiotic to the subject.

17. The method of claim 14 , wherein the subject has a bacterial infection.

18. The method of claim 17 , wherein the subject is undergoing treatment with an antibiotic.

19. The method of claim 17 , wherein the subject has a Gram-positive bacterial infection.

20. The method of claim 19 , wherein the subject has a methicillin-resistant Staphylococcus aureus infection.

Assignments (1)

Continuity (2)

References Cited (245)