Granted Patent B2

US 12,202,810 · App. 18/206,925 · Granted Jan 21, 2025

Inventors: Paul S. Shapiro (Baltimore, MD); Alexander D. Mackerell, Jr. (Baltimore, MD); Jeffrey D. Hasday (Timonium, MD); Steven Fletcher (Baltimore, MD)

Assignee: University of Maryland, Baltimore

C07D295/03

Abstract

Claims (22)

1. A compound of the formula:

or a pharmaceutically acceptable salt thereof, wherein,

L 1 is selected from —CH 2 —, —C(CH 3 ) 2 —, and —C(CH 2 CH 2 )—;

L 2 is selected from —NH—SO 2 —, —NHCH 2 —, —CH 2 NH—, —NHCO—, —CONH—, and —SO 2 NH—; and

each of R 1a and R 2a is independently selected from hydrogen, C 1-10 alkyl, and C 1-10 alkyl substituted by one or more of substituents which are independently hydroxy, halo, cyano, trifluoromethyl, trifluoromethoxy, nitro, trimethylsilanyl, —OR a , —SR a , —S(O) t R a (wherein t is 1 or 2), —OC(O)—R a , —N(R a ) 2 , —C(O)R a , —C(O)OR a , —OC(O)N(R a ) 2 , —C(O)N(R a ) 2 , —N(R a )C(O)OR a , —N(R a )C(O)R a , —N(R a )C(O)N(R a ) 2 , —N(R a )C(NR a )N(R a ) 2 , —N(R a )S(O) t R a (wherein t is 1 or 2), —S(O) t R a (wherein t is 1 or 2), —S(O) t OR a (wherein t is 1 or 2), —S(O) t N(R a ) 2 (wherein t is 1 or 2), or —PO(OR a ) 2 wherein each R a is independently hydrogen and C 1-3 alkyl.

2. The compound of claim 1 , wherein L 1 is —CH 2 —.

3. The compound of claim 1 , wherein L 2 is —NH—SO 2 —.

4. The compound of claim 1 , wherein L 2 is —NHCH 2 —.

5. The compound of claim 1 , wherein L 2 is —CH 2 NH—.

6. The compound of claim 1 , wherein L 2 is —NHCO—.

7. The compound of claim 1 , wherein L 2 is —CONH—.

8. The compound of claim 1 , wherein L 2 is —SO 2 —NH—.

9. The compound of claim 1 , wherein each of R 1a and R 2a is independently selected from hydrogen and C 1-3 alkyl.

10. The compound of claim 1 , wherein each of R 1a and R 2a is independently C 1-3 alkyl.

11. A pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof.

12. The pharmaceutical composition of claim 11 , wherein the pharmaceutical composition is an oral pharmaceutical composition.

13. The pharmaceutical composition of claim 11 , wherein the pharmaceutical composition is an oral dosage form.

14. A method of treating an inflammatory disease in a patient comprising administering to a patient in need thereof a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the inflammatory disease is selected from rheumatoid arthritis, a cardiovascular disease, multiple sclerosis, inflammatory bowel disease, chronic obstructive pulmonary disease (COPD), asthma, acute respiratory distress syndrome (ARDS), and acute lung injury (ALI).

15. The method of claim 14 , wherein the disease is a respiratory disease.

16. The method of claim 14 , wherein administering comprises orally administering.

17. The method of claim 14 , wherein administering comprises administering an oral dosage form comprising the compound.

18. The method of claim 14 , wherein administering comprises administering from 0.1 mg/kg to 200 mg/kg of the compound.

Assignments (1)

Continuity (5)

References Cited (129)