P
USRE40246EExpiredUtilityPatentIndex 50

Method for the suppression of viral growth

Assignee: UNIV JOHNS HOPKINSPriority: Sep 30, 1994Filed: Sep 17, 2003Granted: Apr 15, 2008
Est. expirySep 30, 2014(expired)· nominal 20-yr term from priority
Inventors:HUANG RU CHIH CGNABRE JOHN N
A61K 31/05A61K 31/09C07C 69/017C07C 43/23A61K 31/085A61K 31/222A61P 31/18A61P 31/12A61P 37/00
50
PatentIndex Score
0
Cited by
30
References
37
Claims

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

exact text as granted — not AI-modified
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:

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