Small molecules that sensitize HIV-1 infected cells to antibody dependent cellular cytotoxicity

Patent metadata

Field	Value
Publication number	US-12286401-B2
Application number	US-201917263590-A
Country	US
Kind code	B2
Filing date	Jul 31, 2019
Priority date	Jul 31, 2018
Publication date	Apr 29, 2025
Grant date	Apr 29, 2025

Abstract

Compounds and methods 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 are provided. The compounds are of formula (I), (II), and (IA), wherein R 1 -R 7 , X, X′, Y, Y′, Z, and n are defined herein, and the methods comprises administering therapeutically effective amounts of these compounds to the human.

First claim

What is claimed:

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:

Assignees

• Univ Pennsylvania
• Val Chum Lp

Inventors

• Davies Melissa Carey
• Smith Iii Amos B
• Finzi Andres
• Ding Shilei
• Chapleau Jean-Philippe

Classifications

• C07D413/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D403/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D401/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D309/08

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms · CPC title

• C07D265/30

  not condensed with other rings · CPC title