Treatment and prevention of hepatic disorders

• US 6,218,437 B1
• Filed: 09/21/1999
• Issued: 04/17/2001
• Est. Priority Date: 09/30/1996
• Status: Expired due to Fees

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Chojkier, Mario
• Primary Examiner(s): AULAKH, CHARANJIT
• Application Number:
  US09/400,322
• Time in Patent Office: 574 Days
• Field of Search: 514/567, 514/731, 562/454, 562/433, 568/716
• US Class Current: 514/731
• CPC Class Codes: A61K 31/05 Phenols cannabinoids A61K31/658
• CPC Class Codes: A61K 31/355 Tocopherols, e.g. vitamin E
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir

Abstract

The present invention provides new methods for the treatment of viral hepatitis C involving the administration of vitamin E and other compounds with antioxidant properties. Treatment with high doses of vitamin E is effective in treating chronic hepatitis C in patients refractory to interferon. In addition, new methods are described for the treatment of hepatic fibrosis and hepatic conditions manifesting hepatic fibrosis involving the administration of butylated hydroxytoluene and a metabolite of pentoxifylline, 1-[3-carboxypropyl]-3, 7-dimethylxanthine. Furthermore, new methods are described for the treatment and prevention of hepatic disorders involving the use of 2,6-di-tert-butylphenol derivatives.

Claims

1. A method of treating hepatitis C, comprising:

a) providing i) a subject having symptoms of hepatitis C, and ii) a 2,6-di-tert-butylphenol derivative having the structure

wherein X is a low molecular weight alkyl chain which terminates with an unsaturated functional group; and

b) administering a therapeutic amount of said di-tert-butylphenol derivative to said subject under conditions such that said symptoms are diminished.

2. The method of claim 1, wherein said 2,6-di-tert-butylphenol derivative is selected from the group consisting of 4-propynoyl-2,6-di-tert-butylphenol, 4-(1′

-hydroxy-2′

-propynyl)-2,6-di-tert-butylphenol, 4-(3′

-butynoyl)-2,6-di-tert-butylphenol, 4-butylphenol-2,6-di-tert-butylphenol, 4-(4′

-pentynoyl)-2,6-di-tert-butylphenol, 4-(4′

-pentenoyl)-2,6-di-tert-butylphenol, 4-(2′

-dimethoxymethyl-4′

-pentynoyl)-2,6-di-tert-butylphenol, 4-(2′

,2′

-dimethyl-4′

-pentynoyl)-2,6-di-tert-butylphenol, 4-(3′

,3′

-dimethyl-4′

-pentynoyl)-2,6-di-tert-butylphenol, 4-(4′

-pentyn-3′

one)-2,6-di-tert-butylphenol, 4-(5′

-hexynoyl)-2,6-di-tert-butylphenol, 4-(5′

-hexenoyl)-2,6-di-tert-butylphenol, 4-(2′

-methyl-5′

-hexynoyl)-2,6-di-tert-butylphenol, 4-(1′

-hydroxy-5′

-hexynyl)-2,6-di-tert-butylphenol, 4-(5′

-hexynoyl)-2,6-di-tert-butylphenol, 4-(1′

-methylidine-5′

-hexynyl)-2,6-di-tert-butylphenol, 4-[(S)-(−

)-3′

-methyl-5′

-hexynoyl]-2,6-di-tert-butylphenol, 4-[(R)-(+)-3′

-methyl-5′

-hexynoyl)-2,6-di-tert-butylphenol, 4-(6′

-heptynoyl)-2,6-di-tert-butylphenol, 4-(6′

-heptyn-3′

-one)-2,6-di-tert-butylphenol, 4-[4′

-(2″

-propynyl)-6′

-heptyn-3′

-one]-2,6-di-tert-butylphenol, 4-(7′

-octynoyl)-2,6-di-tert-butylphenol, 4-[(E)-1′

-penten-4′

-yn-3′

-one)-2,6-di-tert-butylphenol, 4-[(E)-1′

,6′

-heptadiene-3′

-one)-2,6-di-tert-butylphenol, 4-(3′

,3′

-dimethoxypropionyl)-2,6-di-tert-butylphenol, 4-[2′

-(1″

,3″

-dioxolane)acetyl]-2,6-di-tert-butylphenol, 4-(3′

,3′

-diethoxypropionyl)-2,6-di-tert-butylphenol, 4-[2′

-(1″

,3″

-oxathiolaneacetyl]-2,6-di-tert-butylphenol, 4-(2′

,2′

-dimethoxyethyl-2,6-di-tert-butylphenol, 4-(5′

,5′

-dimethoxy-3′

-pentanone)-2,6-di-tert-butylphenol, 4-(3′

,3′

-dimethyl-5′

-hexynoyl)-2,6-di-tert-butylphenol, [3-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]-methylene]dihydro-2(3H)-furanone, N-methoxy-3-(3,5-di-tert-butyl-4-hydroxybenzylidine)-pyrrolidin-2-one, 5-{[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methylene}-4-thiazolidine, 5-{[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methylene}-4-N-methylthiazolidine, R-830, CI-1004 and R-840] and N-3,5-bis(1,1-dimethylethyl)-4hydroxphenyl-3-aminobenzoic acid.

3. The method of claim 2, wherein said 2,6-di-tert-butylphenol derivative is selected from the group consisting of 4-(5′

-hexynoyl)-2,6-di-tert-butylphenol, [3-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]-methylene]dihydro-2(3H)-furanone, N-methoxy-3-(3,5-di-tert-butyl-4-hydroxybenzylidine)-pyrrolidin-2-one, and N-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]-3-aminobenzoic acid] and N-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]-3-aminobenzoic acid.

4. The method of claim 1, wherein said subject is refractory to interferon.

5. The method of claim 1, wherein said di-tert-butylphenol derivative is administered orally to said subject.

6. The method of claim 1, wherein said di-tert-butylphenol derivative is administered parenterally to said subject.

7. The method of claim 1, further comprising the step prior to step b) of measuring said symptoms by liver biopsy.

8. The method of claim 7, further comprising the step subsequent to step b) of measuring said symptoms by liver biopsy.