Granted Patent B2

US 12,286,401 · App. 17/263,590 · Granted Apr 29, 2025

Inventors: Melissa Carey Davies (Arlington, MA); Amos B. Smith, III (Merion, PA); Andres Finzi (Quebec, CA); Shilei Ding (Quebec, CA); Jean-Philippe Chapleau (Quebec, CA)

Assignees: THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA; VAL-CHUM, LIMITED PARTNERSHIP

C07D211/96A61P31/18C07D207/48C07D211/56C07D211/60C07D215/54C07D241/04C07D265/30C07D309/08C07D401/12C07D403/12C07D413/12

Abstract

Claims (45)

1. A method of treating HIV-1 in a human infected with HIV-1 or preventing HIV-1 infection in a human susceptible to infection with HIV-1 comprising administering to the human a therapeutically effective amount of a compound of formula (I):

wherein:

n is 1;

X is —CH 2 —;

Y is —N(C(O)OC 1-6 alk)-, —N(SO 2 R 9 )—, —N(C(O)R 8 )—, —N(C(O)NR 9 R 10 )—, or —N(C(═NH)NR 9 R 10 )—;

Z is C(O)NH—;

R 1 is H;

R 2 is H;

(i) R 3 is H, halogen, C 1-6 alkyl, —OC 1-6 alkyl, or C 1-6 haloalkyl; and R 4 is halogen; or (ii) R 3 is halo or C 1-6 haloalkyl; and R 4 is H;

R 5 is H, halogen, C 1-6 alkyl, —OC 1-6 alkyl, or C 1-6 haloalkyl;

R 6 and R 7 are each H or NH 2 ;

R 8 is —OC 1-6 alkyl, —O—C 1-6 alk-NH 2 , —NH(C 1-6 alkyl), —N(C 1-6 alkyl)(C 1-6 alkyl), —NH—C 1-6 alk-NH 2 , phenyl, or heteroaryl; and

R 9 and R 10 are, independently, H, C 1-6 alkyl, —C(O)OC 1-6 alkyl, halogenated C 1-6 alkyl, C 3-8 cycloalkyl, aryl, or heteroaryl;

wherein R 8 , R 9 , and R 10 are, independently, optionally substituted by halo, CN, OC 1-6 alkyl, —NHC(O)(C 1-6 alkyl), or unsubstituted C 1-6 alkyl;

or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , wherein Y is —N(SO 2 R 9 ).

3. The method of claim 1 , wherein Y is —N(C(O)R 8 )—.

4. The method of claim 3 , wherein Y is —N(C(O)—OC 1-6 alkyl).

5. The method of claim 1 , wherein Y is —N(C(O)NR 9 R 10 )—.

6. The method of claim 1 , wherein Y is —N(C(═NH)NR 9 R 10 )—.

7. The method of claim 1 , wherein:

R 3 is Cl and R 5 is H;

R 3 is F and R 5 is H;

R 3 is Br and R 5 is H;

R 3 is CF 3 and R 5 is H;

R 4 is Cl and R 3 and R 5 is H;

R 4 is Br and R 3 and R 5 is H;

R 4 is F and R 3 and R 5 is H;

R 5 is H;

R 5 is H, R 3 is Cl and R 4 is F;

R 5 is H, R 3 is F and R 4 is Cl;

R 5 is H, R 3 is Cl are R 4 is Br;

R 5 is H, R 3 is Br are R 4 is Cl;

R 5 is H, R 3 and R 4 are Cl;

R 5 is H, R 3 and R 4 are F;

R 5 is H, R 3 is CF 3 and R 4 is F;

R 3 is H, R 4 is F and R 5 is Cl; or

R 3 is H, R 4 is Cl and R 5 is F.

8. The method of claim 1 , wherein Y is —N(SO 2 R 9 )—.

9. The method of claim 1 , wherein the compound is of formula (III), (V), (VI), (VII), (VIII), (IX), or (X):

10. The method of claim 1 , wherein the compound is:

11. The method of claim 1 , wherein the compound is:

12. The method of claim 11 , wherein the compound is:

13. The method of claim 1 , wherein the compound is:

14. The method of claim 2 , wherein Y is —N(SO 2 -aryl)- or —N(SO 2 -heteroaryl)-.

Assignments (4)

Continuity (2)

References Cited (150)