Benzoannulene derivatives as antiviral agents

Patent metadata

Field	Value
Publication number	US-11066357-B2
Application number	US-201816954464-A
Country	US
Kind code	B2
Filing date	Dec 24, 2018
Priority date	Dec 26, 2017
Publication date	Jul 20, 2021
Grant date	Jul 20, 2021

Abstract

The present disclosure is concerned with benzoannulene compounds that are capable of inhibiting a viral infection and methods of treating viral infections such as, for example, chikungunya, Venezuelan equine encephalitis, dengue, influenza, and zika, using these compounds. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

First claim

What is claimed is:

1. A compound having a structure represented by a formula:

wherein each of m and n is independently selected from 0 and 1;
wherein Q is selected from CH and N;
wherein Z is selected from NH and CH 2 ;
wherein R 1 is selected from hydrogen, —OH, C1-C4 alkyl, C1-C4 haloalkoxy, and C1-C4 alkoxy;
wherein R 2 is hydrogen; and
wherein R 3 is C2-C5 heteroaryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, —CN, —NH 2 , —OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, (C1-C4 alkyl)Ar 1 , and Ar 1 ;
wherein Ar 1 , when present, is selected from cycloalkyl, monocyclic aryl, heterocycloalkyl, and heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, C1-C4 alkyl, and C1-C4 haloalkyl;

or wherein R 3 is a structure represented by a formula:

wherein each of R 4a , R 4b , R 4c , and R 4d is independently selected from hydrogen, halogen, —CN, —NH 2 , —OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, and Ar 2 ;
wherein Ar 2 , when present, is selected from cycloalkyl, monocyclic aryl, heterocycloalkyl, and heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, C1-C4 alkyl, and C1-C4 haloalkyl;

wherein R 5 is selected from hydrogen, halogen, —CN, —NH 2 , —OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, —(C1-C4 alkyl)CO 2 H, and Ar 3 ; and
wherein Ar 3 , when present, is selected from cycloalkyl, monocyclic aryl, heterocycloalkyl, and heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, C1-C4 alkyl, and C1-C4 haloalkyl;

or wherein each of R 2 and R 3 are covalently bonded together and, together with the intermediate atoms, comprise a 3- to 6-membered heterocycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, —CN, —NH 2 , —OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino;
provided that when n is 1 and R 1 is hydrogen, then R 3 is not pyridinyl,
provided that when n is 1, then R 5 is not hydrogen,
or provided that when R 5 is hydrogen, then R 1 is not hydrogen,
or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein m is 0.

3. The compound of claim 1 , wherein n is 0 and R 5 is not hydrogen.

4. The compound of claim 1 , wherein each of m and n is 0.

5. The compound of claim 4 , wherein R 5 is not hydrogen.

6. The compound of claim 1 , wherein R 1 is selected from —OH and C1-C4 alkoxy.

7. The compound of claim 1 , wherein R 3 is C2-C5 heteroaryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, —CN, —NH 2 , —OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, (C1-C4 alkyl)Ar 1 , and Ar 1 .

8. The compound of claim 7 , wherein R 3 is selected from pyrazolyl, thiazolyl, and pyridinyl.

9. The compound of claim 7 , wherein R 3 is a structure:

10. The compound of claim 1 , wherein R 3 is a structure represented by a formula:

11. The compound of claim 10 , wherein R 3 is a structure:

12. The compound of claim 1 , wherein each of R 2 and R 3 are covalently bonded together and, together with the intermediate atoms, comprise a 3- to 6-membered heterocycloalkyl substituted with 0, 1, 2, or 3 groups independently selected from halogen, —CN, —NH 2 , —OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 alkylamino, and (C1-C4)(C1-C4) dialkylamino.

13. The compound of claim 1 , wherein the compound has a structure represented by a formula:

14. The compound of claim 1 , wherein the compound has a structure represented by a formula:

wherein R 1 is selected from hydrogen, —OH, C1-C4 alkyl, and C1-C4 alkoxy; and
wherein R 3 is heteroaryl substituted with 0, 1, 2, or 3 groups independently selected from halogen, —CN, —NH 2 , —OH, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4)(C1-C4) dialkylamino, (C1-C4 alkyl)Ar 1 , and Ar 1 .

15. The compound of claim 1 , wherein the compound has a structure represented by a formula:

16. The compound of claim 1 , wherein the compound is selected from:

17. The compound of claim 1 , wherein the compound is selected from:

18. A pharmaceutical composition comprising a therapeutically effective amount of at least one compound of claim 1 and a pharmaceutically acceptable carrier.

19. A method for the treatment of a viral infection in a subject having the viral infection, the method comprising the step of administering to the subject a therapeutically effective amount of at least one compound of claim 1 , wherein the subject has been diagnosed as having the viral infection prior to the administering step.

20. The method of claim 19 , wherein the viral infection is selected from chikungunya, Venezuelan equine encephalitis, dengue, influenza, and zika.

Assignees

• Southern Res Inst

Inventors

• Pathak Ashish Kumar
• Ahmed Syed Kaleem
• Suto Mark J
• Augelli-Szafran Corinne E

Classifications

• C07D231/40 Primary

  Acylated on said nitrogen atom · CPC title

• C07D211/16

  with acylated ring nitrogen atom · CPC title

• C07C255/42

  the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being further bound to other hetero atoms · CPC title

• C07D401/12

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

• C07D275/02

  not condensed with other rings · CPC title