Benzo annulenes as antiviral agents

• US 10,450,263 B2
• Filed: 02/08/2018
• Issued: 10/22/2019
• Est. Priority Date: 02/10/2017
• Status: Active Grant

• Current Assignee: Southwest Research Institute
• Original Assignee: Southwest Research Institute
• Inventors: Pathak, Ashish Kumar, Ahmed, Syed Kaleem, Augelli-Szafran, Corinne E., Maddry, Joseph A.
• Primary Examiner(s): Kifle, Bruce
• Application Number:
  US15/892,302
• Publication Number:
  US 20180230084A1
• Time in Patent Office: 621 Days
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: C07C 233/29 having the carbon atom of the carboxamide group bound to an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
• CPC Class Codes: C07C 233/60 having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
• CPC Class Codes: C07C 233/65 having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
• CPC Class Codes: C07C 233/75 with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 235/48 having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
• CPC Class Codes: C07C 255/33 with cyano groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by saturated carbon chains
• CPC Class Codes: C07C 255/41 the carbon skeleton being further substituted by carboxyl groups, other than cyano groups
• CPC Class Codes: C07C 255/58 containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the carbon skeleton
• CPC Class Codes: C07C 2601/02 with a three-membered ring
• CPC Class Codes: C07C 2601/04 with a four-membered ring
• CPC Class Codes: C07C 2602/12 the other ring being at least seven-membered
• CPC Class Codes: C07C 2603/74 Adamantanes
• CPC Class Codes: C07C 311/21 having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07D 209/46 with an oxygen atom in position 1
• CPC Class Codes: C07D 213/30 Oxygen atoms
• CPC Class Codes: C07D 213/56 Amides
• CPC Class Codes: C07D 213/81 Amides; Imides
• CPC Class Codes: C07D 223/16 Benzazepines; Hydrogenated benzazepines
• CPC Class Codes: C07D 231/14 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 Class Codes: C07D 233/90 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 239/28 : with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
• CPC Class Codes: C07D 241/24 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 261/18 : Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen
• CPC Class Codes: C07D 271/12 : condensed with carbocyclic rings or ring systems
• CPC Class Codes: C07D 277/56 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07D 307/68 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07D 307/85 : attached in position 2
• CPC Class Codes: C07D 309/08 : 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 Class Codes: C07D 333/38 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Abstract

The present disclosure is concerned with benzo annulene 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.

Claims

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

2. The compound of claim 1, wherein Z is CH₂.

3. The compound of claim 1, wherein each of R^1a and R^1b is hydrogen.

4. The compound of claim 1, wherein R² is —

OR²⁰.

5. The compound of claim 1, wherein Cy¹ is selected from phenyl and 5-6 membered heteroaryl having 1-3 heteroatoms selected from nitrogen, oxygen, sulfur, and phosphorous, and substituted with 0, 1, or 2 groups independently selected from halogen, —

CO₂H, —

CN, —

OH, —

NH₂, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkylnitrile, C1-C8 hydroxyalkyl, C1-C8 alkoxy, C1-C8 halohydroxyalkyl, C1-C8 aminoalkyl, C1-C8 alkylamino, (C1-C8)(C1-C8) dialkylamino, and Cy².

6. The compound of claim 1, wherein Cy¹ is phenyl substituted with 0, 1, or 2 groups independently selected from halogen, —

CO₂H, —

CN, —

OH, —

NH₂, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkylnitrile, C1-C8 hydroxyalkyl, C1-C8 alkoxy, C1-C8 halohydroxyalkyl, C1-C8 aminoalkyl, C1-C8 alkylamino, (C1-C8)(C1-C8) dialkylamino and Cy².

7. The compound of claim 1, wherein Cy¹ is phenyl substituted with a tert-butyl group.

8. The compound of claim 1, wherein Cy¹ is 5-6 membered heteroaryl having 1-3 heteroatoms selected from nitrogen, oxygen, sulfur, and phosphorous, substituted with 0, 1, or 2 groups independently selected from halogen, —

CO₂H, —

CN, —

OH, —

NH₂, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkylnitrile, C1-C8 hydroxyalkyl, C1-C8 alkoxy, C1-C8 halohydroxyalkyl, C1-C8aminoalkyl, C1-C8alkylamino, (C1-C8)(C1-C8) dialkylamino, Cy¹, and Ar³.

9. The compound of claim 1, wherein Cy¹ is selected from thiazole, pyrazole, imidazole, furan, thiophene, isoxazole, pyrimidine, and pyridine and substituted with 0, 1, or 2 groups independently selected from halogen, —

CO₂H, —

CN, —

OH, —

NH₂, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkylnitrile, C1-C8 hydroxyalkyl, C1-C8 alkoxy, C1-C8 halohydroxyalkyl, C1-C8 aminoalkyl, C1-C8 alkylamino, (C1-C8)(C1-C8) dialkylamino, Cy¹, and Ar³.

10. The compound of claim 1, wherein Cy¹ is C3-C10 cycloalkyl and substituted with 0, 1, or 2 groups independently selected from halogen, —

CO₂H, —

CN, —

OH, —

NH₂, C1-C8 alkyl, C1-C8 haloalkyl, C1-C8 alkylnitrile, C1-C8 hydroxyalkyl, C1-C8 alkoxy, C1-C8 halohydroxyalkyl, C1-C8 aminoalkyl, C1-C8 alkylamino, (C1-C8)(C1-C8) dialkylamino, and Cy².

11. The compound of claim 1, wherein Cy¹ is unsubstituted adamantine.

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

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:

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

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

16. A pharmaceutical composition comprising a therapeutically effective amount of at least one compound having a structure represented by a formula selected from:

17. A method for the treatment of chikungunya in a subject, the method comprising the step of administering to the subject an effective amount of at least one compound having a structure represented by a formula selected from:

18. The method of claim 17, wherein the subject has been diagnosed with a need for treatment of chikungunya prior to the administering step.