ANTIVIRAL POLYMERS

Abstract

The present invention relates to polymer compounds that have antiviral activity. The compounds have the structural Formula I defined herein. The present invention also relates to processes for the preparation of these compounds, to compositions comprising them, and to their use in the prevention or treatment of viral infections.

Description

Claims

1. A branched polymer according to Formula I: whereinis a polyvalent core structure;X is a monomer residue comprising at least one sulfonate or sulfate substituent;Y is a monomer residue;Z is a capping group;m is greater than or equal to 3;n is 5 to 500;p is 1 to 500; andq is 0 to 200; wherein if q is greater than 1, then at each occurrence, Y may be the same or different residues.

2. A branched polymer according to claim 1, wherein X has a structure according to Formula II: whereinR1 is aryl, C1-20alkyl, C1-20alkylene-aryl, C(O)OR4, C(O)NHR4, OC(O)R4, NHC(O)R4, or sulfonate;R2 and R3 are independently selected from hydrogen and C1-4alkyl; andR4 is C1-10alkyl or aryl; and wherein each of the aryl, C1-20alkyl, C1-20alkylene-aryl, or R4 groups is substituted with one or more sulfonate or sulfate groups, and is optionally substituted with one or more substituents selected from hydroxy, halo, C1-4alkyl, C1-4alkoxy, aryl, and cyano.

3. A branched polymer according to claim 2, wherein R1 is phenyl, C(O)OR4, or C(O)NHR4, wherein R4 is C1-10alkyl and each of the phenyl or R4 groups is substituted with one or more sulfonate groups and is optionally substituted with one or more substituents selected from hydroxy, halo, C1-4alkyl, C1-4alkoxy, and cyano.

4. A branched polymer according to claim 2, wherein R1 is selected from: wherein L2 is C1-20alkylene.

5. A branched polymer according to any one of claims 2 to 4, wherein R2 and R3 are independently selected from hydrogen and methyl,.

6. A branched polymer according to any one of claims 2 to 4, wherein R2 is hydrogen or methyl and R3 is hydrogen.

7. A branched polymer according to any one of claims 1 to 6, wherein n is 5 to 400, such as 5 to 300, 10 to 250, or conveniently 20 to 100.

8. A branched polymer according to any one of claims 1 to 7, wherein Z is selected from hydrogen, hydroxyl, bromo, chloro, or one of the following groups: wherein:R5 is hydrogen, halo, cyano, CO2H, C1-3haloalkyl, C1-3alkylene-OH, or C1-3alkylene-NH2;R6 and R7 are independently chosen from hydrogen and C1-3alkyl optionally substituted with cyano, halo, or CO2H;R3 is S-C1-15alkyl, S-aryl, NR9R10 or aryl, said C1-15alkyl and aryl groups being optionally substituted with one or more substituents selected from hydroxy, C1-3alkyl, halo, cyano, CO2H, and C1-3haloalkyl;R9 is hydrogen or C1-3alkyl; andR10 is hydrogen, C1-12alkyl or aryl, said C1-12alkyl and aryl groups being optionally substituted with one or more substituents selected from hydroxy, C1-3alkyl, halo, cyano, CO2H, and C1-3haloalkyl.

9. A branched polymer according to any one of claims 1 to 7, wherein Z is selected from one of the following groups: .

10. A branched polymer according to any one of claims 1 to 9, wherein p is 5 to 400, such as 5 to 300, 10 to 250, or conveniently 20 to 150.

11. A branched polymer according to any one of claims 1 to 10, wherein q is 0, or q is 1.

12. A branched polymer according to any one of claims 1 to 11, wherein m is 3 to 12, such as 4 to 10, or conveniently 4 or 6.

13. A branched polymer according to any one of claims 1 to 11, wherein is selected from:whereinT is O, S or NH;R11 is hydrogen or C1-4alkyl; andL1 is selected from one of the following linker groups: and wherein is the point of attachment to T and * is the point of attachment to an X residue;R12 and R13 are independently chosen from hydrogen, C1-3alkyl, hydroxy, and halo;r is 1 to 10; andR14 and R15 are independently chosen from hydrogen and C1-3alkyl.

14. A branched polymer according to claim 13, wherein L1 is selected from: and Z is selected from:.

15. A branched polymer according to claim 13, wherein L1 is and Z is:.

16. A branched polymer according to claim 13, wherein L1 is and Z is bromo or chloro.

17. A branched polymer according to any one of claims 13 to 16, wherein T is O.

18. A branched polymer according to claim 1 wherein X is: n is 10 to 100, q is 0, and m is 4.

19. A composition comprising a branched polymer according to any one of claims 1 to 18, or a salt or salts thereof.

20. A method of sterilisation or viral disinfection, comprising using an effective amount of the composition of claim 19.

21. A device for sterilisation or viral disinfection comprising the composition of claim 19 and means for dispensing the composition.

22. A pharmaceutical composition comprising a branched polymer according to any one of claims 1 to 18, or a pharmaceutically acceptable salt or salts thereof, and one or more pharmaceutically acceptable excipients.

23. A branched polymer according to any one of claims 1 to 18, or a pharmaceutical composition according to claim 22, or a pharmaceutically acceptable salt or salts thereof, for use in the prevention or treatment of viral infections.

24. The branched polymer or pharmaceutical composition for use in the prevention or treatment of viral infections according to claim 23, wherein the viral infection is associated with herpes simplex virus (HSV), adenovirus, adeno-associated virus, human papillomavirus (HPV), respiratory syncytial virus (RSV), dengue virus, norovirus, lentivirus, human immunodeficiency virus (HIV), human cytomegalovirus (HCMV), human metapneumovirus (HMPV), human parainfluenza virus type 3 (HPIV-3), coronavirus (such as MERS-CoV, SARS-CoV, or SARS-CoV-2), foot-and-mouth disease virus, hepatitis B virus, hepatitis C virus, Ebola virus, nipah virus, Rift Valley fever virus, West Nile virus, Crimean Congo virus, Toscana virus, ZIKA virus, Chickungunya virus (CHIKV), Akabane virus (AKAV) or Schmallenberg virus (SBV), influenza (such as Influenza A H3N2 or H1N1 virus), adeno-associated virus (AAV), Newcastle disease virus (NDV), or vesicular stomatitis virus (VSV).

25. A material comprising a branched polymer according to any one of claims 1 to 18, or a salt, or salts, thereof.