Compositions useful for inhibiting HIV-1 infection and methods using same

Patent metadata

Field	Value
Publication number	US-9920073-B2
Application number	US-201415025429-A
Country	US
Kind code	B2
Filing date	Oct 3, 2014
Priority date	Oct 4, 2013
Publication date	Mar 20, 2018
Grant date	Mar 20, 2018

Abstract

The present invention includes novel compositions useful for preventing or treating an HIV-1 infection in a subject in need thereof. The present invention further includes a novel method of preventing or treating an HIV-1 infection in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of the invention. In certain embodiments, the subject is further administered at least one additional therapeutic agent.

First claim

What is claimed is:

1. A compound of formula (I), or a salt or solvate thereof:

wherein:
R 1 is

ring A is

wherein the atom labeled with A is linked to ring R 1 ;

linker L is selected from the group consisting of:

wherein the atom labeled with B is linked to ring B;

ring B is selected from the group consisting of:

each occurrence of R 2 is independently selected from the group consisting of —(C 1 -C 6 )alkyl, —(C 1 -C 6 )fluoroalkyl, —F, —Cl, —Br, —I, and —OR 7 ;
R 4 is 1,2,4-triazolyl optionally substituted with (C 1 -C 6 )alkyl;
R 5 is selected from the group consisting of H, —(C 1 -C 6 )alkyl, —(C 1 -C 6 )fluoroalkyl, and —OR 7 ;
R 6 is H or F;
each occurrence of R 7 is independently selected from the group consisting of H and —(C 1 -C 6 )alkyl;
X is CH or N;
x is an integer from 0-5; and
each occurrence of n is independently 0 or 1.

2. The compound of claim 1 , wherein R 1 is

3. The compound of claim 1 , wherein the compound is N-(3-benzoyl-3-azabicyclo[3.1.0]hexan-6-yl)-3-(4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2,3-dioxopropanamide (SC28), or a salt, N-oxide or solvate thereof.

4. A pharmaceutical composition comprising at least one compound of claim 1 and at least one pharmaceutically acceptable carrier.

5. The composition of claim 4 , further comprising at least one additional therapeutic agent useful for treating an HIV infection.

6. The composition of claim 5 , wherein the at least one additional therapeutic agent comprises at least one selected from the group consisting of a HIV drug combination, entry and fusion inhibitor, integrase inhibitor, non-nucleoside reverse transcriptase inhibitor, nucleoside reverse transcriptase inhibitor, and protease inhibitor.

7. A method of treating an HIV-1 infection in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of at least one compound of formula (I):

wherein:
R 1 is

ring A is

wherein the atom labeled with A is linked to ring R 1 ;

linker L is selected from the group consisting of:

wherein the atom labeled with B is linked to ring B;

ring B is selected from the group consisting of:

each occurrence of R 2 is independently selected from the group consisting of —(C 1 -C 6 )alkyl, —(C 1 -C 6 )fluoroalkyl, —F, —Cl, —Br, —I, and —OR 7 ;
R 4 is 1,2,4-triazolyl optionally substituted with (C 1 -C 6 )alkyl;
R 5 is selected from the group consisting of H, —(C 1 -C 6 )alkyl, —(C 1 -C 6 )fluoroalkyl, and —OR 7 ;
R 6 is H or F;
each occurrence of R 7 is independently selected from the group consisting of H and —(C 1 -C 6 )alkyl;
X is CH or N;
x is an integer from 0-5; and
each occurrence of n is independently 0 or 1;
a salt, solvate, or N-oxide thereof, and any combinations thereof.

8. The method of claim 7 , wherein R 1 is

9. The method of claim 7 , wherein the compound is N-(3-benzoyl-3-azabicyclo[3.1.0]hexan-6-yl)-3-(4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2,3-dioxopropanamide (SC28); or a salt, N-oxide or solvate thereof.

10. The method of claim 7 , wherein the method further comprises administering to the subject at least one additional therapeutic agent useful for treating HIV infection.

11. The method of claim 10 , wherein the at least one additional therapeutic agent comprises at least one selected from the group consisting of a HIV drug combination, entry and fusion inhibitor, integrase inhibitor, non-nucleoside reverse transcriptase inhibitor, nucleoside reverse transcriptase inhibitor, and protease inhibitor.

12. The method of claim 10 , wherein the compound and the at least one additional therapeutic agent are co-administered to the subject.

13. The method of claim 12 , wherein the compound and the at least one additional therapeutic agent are coformulated.

14. The method of claim 7 , wherein the subject is a mammal.

15. The method of claim 14 , wherein the mammal is human.

Assignees

• Univ Drexel

Inventors

• Cocklin Simon

Classifications

• A61K31/495

  having six-membered rings with two {or more} nitrogen atoms as the only ring heteroatoms, e.g. piperazine {or tetrazines}(A61K31/48 takes precedence {; with three nitrogen atoms A61K31/53}) · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title

• A61K31/506

  not condensed and containing further heterocyclic rings · CPC title

• C07D471/04

  Ortho-condensed systems · CPC title

• A61K31/407

  condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine · CPC title