IP Library Granted Patent US 40,246
Granted Patent E1
US 40,246 · App. 10/664,050 · Granted Apr 15, 2008

Method for the suppression of viral growth

Assignee: John Hopkins University
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Quick Facts
Patent No.
US 40,246
App. No.
10/664,050
Granted
Apr 15, 2008
Kind
E1
Abstract

A method for suppressing undesired viral growth in a host which comprises administering to the host an effective amount of a compound of the formula: wherein R 1 , R 2 , R 3 and R 4 are independently selected from the group consisting of HO—, CH 3 O— and CH 3 (C═O) O—. The method is exemplified by inhibiting Tat transactivation of a lentivirus and in suppressing Herpes simplex virus.

Claims (48)

1. A method for suppressing viral growth in a host which consists essentially of administering to the host an effective viral growth suppressing amount of a composition consisting essentially of a compound of the formula:

wherein R 1 , R 2 , R 3 and R 4 are each selected from the group consisting of HO—, CH 3 O— and CH 3 (C═O)O—, provided that R 1 , R 2 , R 3 and R 4 are not each HO—.

2. The method of claim 1 4 , wherein said compound is the water-soluble substituent is —O( C═O ) CH 2 NH ( CH 3 ) 2 .Cl .

3. The method of claim 1 for suppressing 4 , wherein the host is infected with Herpes simplex virus in the host .

4. A method for suppressing viral growth in a host infected with a virus comprising ( a ) providing a composition comprising a substantially purified compound and ( b ) administering said composition to the host in a dosage having an effective amount of the compound to suppress viral growth, wherein the compound is a derivative of nordihydroguaiaretic acid ( NDGA ) having the formula:

wherein R 1 , R 2 , R 3 and R 4 are each selected from the group consisting of HO—, CH 3 O— and CH 3 ( C═ ) O—, or a water soluble substituent, provided that R 1 , R 2 , R 3 and R 4 are not each HO—, wherein the water soluble substituent is selected from the group consisting of: —O ( C═O ) CH 2 NH ( CH 3 ) 2 .Cl, —O ( C═O ) CH 2 NH 2 ,

5. The method of claim 4 , wherein the water- soluble substituent is —O ( C═O ) CH 2 NH 2 .

6. The method of claim 4 , wherein the compound inhibits viral transcription.

7. The method of claim 4 , wherein the compound inhibits transactivation of viral gene.

8. The method of claim 4 , wherein the compound is 1 -( 3 , 4 - dihydroxyphenyl )- 4 -( 3 - hydroxy - 4 - methoxyphenyl )- 2 , 3 - dimethylbutane ( 4 - O - methyl - NDGA ).

9. The method of claim 4 , wherein the compound is 1 -( 3 , 4 - dihydroxyphenyl )- 4 -( 3 - methoxy - 4 - acetoxyphenyl )- 2 , 3 - dimethylbutane ( 3 - O - methyl - 4 - O - acetyl - NDGA ).

10. The method of claim 4 , wherein the compound is 1 -( 3 - methoxy - 4 - hydroxyphenyl )- 4 -( 3 , 4 - dimethoxyphenyl )- 2 , 3 - dimethylbutane ( 3 , 3 ′, 4 - tri - O - methyl - NDGA ).

11. The method of claim 4 , wherein the compound is 1 -( 3 - hydroxy - 4 - methoxyphenyl )- 4 -( 3 , 4 - dimethoxyphenyl )- 2 , 3 - dimethylbutane ( 3 , 4 , 4 ′ - tri - O - methyl - NDGA ).

12. The method of claim 4 , wherein the compound is 1 -( 3 - methoxy - 4 - hydroxyphenyl )- 4 -( 3 - acetoxy - 4 - methoxyphenyl )- 2 , 3 - dimethylbutane ( 3 ′, 4 - di - O - methyl - 3 - O - acetyl - NDGA ).

13. The method of claim 4 , wherein the compound is 1 -( 3 - methoxy - 4 - hydroxyphenyl )- 4 -( 3 - methoxy - 4 - acetoxyphenyl )- 2 , 3 - dimethylbutane ( 3 , 3 ′ - di - O - methyl - 4 - O - acetyl - NDGA ).

14. The method of claim 4 , wherein the compound is 1 -( 3 - hydroxy - 4 - methoxyphenyl )- 4 -( 3 - acetoxy - 4 - methoxyphenyl )- 2 , 3 - dimethylbutane ( 4 , 4 ′ - di - O - methyl - 3 - O - acetyl - NDGA ).

15. The method of claim 4 , wherein the compound is 1 -( 3 - hydroxy - 4 - methoxyphenyl )- 4 -( 3 - methoxy - 4 - acetoxyphenyl )- 2 , 3 - dimethylbutane ( 3 , 4 ′ - di - O - methyl - 4 - O - acetyl - NDGA ).

16. The method of claim 4 , wherein R 1 , R 2 , R 3 and R 4 are not each CH 3 O— or CH 3 ( C═O ) O— simultaneously.

17. The method of claim 4 , wherein the effective viral growth suppressing amount of the compound is less than 95 μM.

18. The method of claim 4 , wherein the effective viral growth suppressing amount of the compound is less than 62 . 7 μM.

19. The method of claim 4 , wherein the effective viral growth suppressing amount of the compound is less than 31 . 3 μM.

20. The method of claim 4 , wherein the effective viral growth suppressing amount of the compound is less than 25 μM.

21. The method of claim 4 , wherein the effective viral growth suppressing amount of the compound is less than 9 . 5 μM.

22. A method of inhibiting replication of an acyclovir- resistant virus in a cell comprising the steps of:

( a ) providing a substantially purified compound having a formula:

wherein R 1 , R 2 , R 3 and R 4 are each selected from the group consisting of HO—, CH 3 O— and CH 3 ( C═O ) O—, and a water soluble substituent, wherein the water soluble substituent is selected from the group consisting of: —O ( C═O ) CH 2 NH ( CH 3 ) 2 .Cl, —O ( C═O ) CH 2 NH 2 ,

( b ) contacting the cell with the compound.

23. A method of treatment of acyclovir- resistant viral infection in a subject comprising the steps of:

( a ) providing a substantially purified compound having the formula:

wherein R 1 , R 2 , R 3 and R 4 are each selected from the group consisting of HO—, CH 3 O— and CH 3 ( C═O ) O—, and a water soluble substituent, wherein the water soluble substituent is selected from the group consisting of: —O ( C═O ) CH 2 NH ( CH 3 ) 2 .Cl, —O ( C═O ) CH 2 NH 2 ,

( b ) administering the substantially purified compound to the subject.

24. A method of treatment of a subject infected with a virus, wherein the virus is resistant to acyclovir comprising the steps of:

( a ) providing a composition comprising a substantially purified compound; and

( b ) administering said composition in a dosage having a therapeutically effective amount of the compound to the subject, wherein the compound has the formula:

wherein R 1 , R 2 , R 3 and R 4 are each selected from the group consisting of HO—, CH 3 O— and CH 3 ( C═O ) O—, and a water soluble substituent, wherein the water soluble substituent is selected from the group consisting of: —O ( C═O ) CH 2 NH ( CH 3 ) 2 .Cl, —O ( C═O ) CH 2 NH 2 ,

25. The method of claim 24 , wherein the water- soluble substituent is —O ( C═O ) CH 2 NH 2 .

26. The method of claim 24 , wherein the water- soluble substituent is —O ( C═O ) CH 2 NH ( CH 3 ) 2 .Cl.

27. The method of claim 24 , wherein the compound inhibits viral transcription.

28. The method of claim 24 , wherein the compound inhibits transactivation of the viral gene.

29. The method of claim 24 , wherein the compound is 1 -( 3 , 4 - dihydroxyphenyl )- 4 -( 3 - hydroxy - 4 - methoxyphenyl )- 2 , 3 - dimethylbutane ( 4 - O - methyl - NDGA ).

30. The method of claim 24 , wherein the compound is 1 -( 3 , 4 - dihydroxyphenyl )- 4 -( 3 - methoxy - 4 - acetoxyphenyl )- 2 , 3 - dimethylbutane ( 3 - O - methyl - 4 - O - acetyl - NDGA ).

31. The method of claim 24 , wherein the compound is 1 -( 3 - methoxy - 4 - hydroxyphenyl )- 4 -( 3 , 4 - dimethoxyphenyl )- 2 , 3 - dimethylbutane ( 3 , 3 ′, 4 - tri - O - methyl - NDGA ).

32. The method of claim 24 , wherein the compound is 1 -( 3 - hydroxy - 4 - methoxyphenyl )- 4 -( 3 , 4 - dimethoxyphenyl )- 2 , 3 - dimethylbutane ( 3 , 4 , 4 ′ - tri - O - methyl - NDGA ).

33. The method of claim 24 , wherein the compound is 1 -( 3 - methoxy - 4 - hydroxyphenyl )- 4 -( 3 - acetoxy - 4 - methoxyphenyl )- 2 , 3 - dimethylbutane ( 3 ′, 4 - di - O - methyl - 3 - O - acetyl - NDGA ).

34. The method of claim 24 , wherein the compound is 1 -( 3 - methoxy - 4 - hydroxyphenyl )- 4 -( 3 - methoxy - 4 - acetoxyphenyl )- 2 , 3 - dimethylbutane ( 3 , 3 ′ - di - O - methyl - 4 - O - acetyl - NDGA ).

35. The method of claim 24 , wherein the compound is 1 -( 3 - hydroxy - 4 - methoxyphenyl )- 4 -( 3 - acetoxy - 4 - methoxyphenyl )- 2 , 3 - dimethylbutane ( 4 , 4 ′ - di - O - methyl - 3 - O - acetyl - NDGA ).

36. The method of claim 24 , wherein the compound is 1 -( 3 - hydroxy - 4 - methoxyphenyl )- 4 -( 3 - methoxy - 4 - acetoxyphenyl )- 2 , 3 - dimethylbutane ( 3 , 4 ′ - di - O - methyl - 4 - O - acetyl - NDGA ).

37. A method of treatment of viral infection in a host comprising the steps of: ( a ) providing a composition comprising a compound; and ( b ) administering said composition in a dosage having a viral inhibitory amount of the compound to the host, wherein the compound has the formula selected from the group consisting of:

Assignments (1)
CONFIRMATORY LICENSE Recorded Oct 30, 2017
From: JOHNS HOPKINS UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 044321/0104 →
Continuity (3)
Reissue 0888249900 · Jun 25, 1997
Continuation In Part 0862758800 · Apr 4, 1996
Division 0831634100 · Sep 30, 1994