Claims
- 1. A method for preventing the onset of an autoimmune or inflammatory disease in a patient at risk for developing an autoimmune or inflammatory disease which method comprises:(a) identifying a patient at risk for developing an autoimmune or inflammatory disease; (b) administering to said patient a pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective autoimmune or inflammatory disease-preventing amount of a compound of formula I: whereinR1 is selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, aralkyl, aryl, cyloalkyl, cycloalkylalkyl and cycloalkenyl; each R2 is independently selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, aralkyl, aryl, alkoxy, substituted alkoxy, cycloalkyl and halo; R3 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, aralkyl, aryl, cycloalkyl and cycloalkylalkyl; R4 is selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, aralkyl, aryl, cycloalkyl, cycloalkylalkyl and cycloalkenyl; and n is an integer ranging from 0 to 2; and optical isomers and racemates thereof, and pharmaceutically acceptable salts thereof.
- 2. The method according to claim 1 wherein the autoimmune disease is systemic lupus or multiple sclerosis.
- 3. The method according to claim 1 wherein the inflammatory disease is rheumatoid arthritis, septic shock, erythema nodosum leprosy, septicemia, uveitis, adult respiratory distress syndrome or inflammatory bowel disease.
- 4. The method of claim 1 wherein n is 0.
- 5. The method of claim 4 wherein R3 is hydrogen.
- 6. The method of claim 5 wherein R1 is a substituted phenyl group having the formula: wherein each R5 is independently selected from the group consisting of alkyl, substituted alkyl, cycloalkyl, aralkyl, aryl, alkoxy, substituted alkoxy, aryloxy, arakyloxy, cycloalkoxy, acyl, acylamino, aminocarbonyl, alkoxycarbonyl, carboxyl, cyano, halo, hydroxy, nitro, sulfonate, thioalkoxy, and —NR6R7, where R6 and R7 are each independently selected from hydrogen, alkyl, substituted alkyl or aryl; or two adjacent R5 groups can be joined together to form an alkylene or alkylenedioxy group; and m is an integer from 1 to 5.
- 7. The method of claim 6 wherein R5 is selected from the group consisting of alkyl, alkoxy, substituted alkoxy, acylamino, thioalkoxy.
- 8. The method of claim 7 wherein R5 is a methyl, methoxy, trifluoromethoxy, acetamido or thiomethoxy group and m is 1 or 2.
- 9. The method of claim 5 wherein R1 is selected from the group consisting of 2-methoxyphenyl, 4-methoxyphenyl, 4-trifluoromethoxyphenyl, 3,5-dimethylphenyl, 4-acetamidophenyl and 4-thiomethoxyphenyl.
- 10. The method of claim 4 wherein R4 is selected from the group consisting of alkyl, substituted alkyl, aralkyl, cycloalkyl and cycloalkylalkyl.
- 11. The method of claim 10 wherein R4 is alkyl or cycloalkyl.
- 12. The method of claim 11 wherein R4 is selected from the group consisting of n-propyl, isopropyl, tert-butyl, cyclopentyl, cyclohexyl and 2,4,4-trimethypent-2-yl.
- 13. The method of claim 1 wherein the compound of formula I is selected from a compound of formula II: wherein each R8 is independently selected from the group consisting of alkyl, alkoxy, acylamino, trifluoromethoxy and thioalkoxy; R9 is selected from the group consisting of alkyl and cycloalkyl; and p is an integer ranging from 1 to 3; and optical isomers and racemates thereof, and pharmaceutically acceptable salts thereof.
- 14. The method of claim 13 wherein R8 is a methyl, methoxy, trifluoromethoxy, acetamido or thiomethoxy group and p is 1 or 2.
- 15. The method of claim 13 wherein R9 is n-propyl, isopropyl, tert-butyl, cyclopentyl, cyclohexyl or 2,4,4-trimethylpent-2-yl.
- 16. The method of claim 1 wherein the compound of formula I is selected from:α-[2-(4-methoxyphenylthio)-5-furyl]-N-tert-butylnitrone, α-[2-(2-methoxyphenylthio)-5-furyl]-N-tert-butylnitrone, α-[2-(4-methoxyphenylthio)-5-furyl]-N-cyclohexylnitrone, α-[2-(4-trifluoromethoxypbenylthio)-5-furyl]-N-tert-butylnitrone, α-[2-(3,5-dimethylphenylthio)-5-furyl]-N-tert-butylnitrone, α-[2-(4-acetamidophenylthio)-5-furyl]-N-tert-butylnitrone, α-[2-(4-ethylphenylthio)-5-furyl]-N-tert-butylnitrone, α-[2-(4-thiomethoxyphenylthio)-5-furyl]-N-tert-butylnitrone, α-[2-(4-methoxyphenylthio)-5-furyl]-N-isopropylnitrone, α-[2-(4-trifluoromethoxypbenylthio)-5-furyl]-N-cyclohexylnitrone, α-[2-(4-methoxyphenylthio)-5-furyl]-N-n-butylnitrone, α-[2-(4-methoxyphenylthio)-5-furyl]-N-n-propylnitrone, α-[2-(4-trifluoromethoxyphenylthio)-5-furyl]-N-isopropylnitrone, α-[2-(4-trifluoromethoxyphenylthio)-5-furyl]-N-n-propylnitrone, α-[2-(4-methoxyphenylthio)-5-furyl]-N-2,4,4-trimethylpent-2-ylnitrone, α-[2-(4-trifluoromethoxyphenylthio)-5-furyl]-N-2,4,4-trimethylpent-2-ylnitrone, α-[2-(4-methoxyphenylthio)-5-furyl]-N-cyclopentylnitrone, or α-[2-(4-trifluoromethoxyphenylthio)-5-furyl]-N-cyclopentylnitrone.
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a continuation of U.S. Ser. No. 09/408,126, filed Sep. 29, 1999 and issued on Oct. 3, 2000 as U.S. Pat. No. 6,127,408; which application is a divisional of U.S. Ser. No. 09/245,130, filed Jan. 14, 1999 and issued on Dec. 7, 1999 as U.S. Pat. No. 5,998,469; which application claims the benefit of U.S. Provisional Application No. 60/071,626, filed Jan. 16, 1998, which application is incorporated herein by reference in its entirety.
Provisional Applications (1)
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Number |
Date |
Country |
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60/071626 |
Jan 1998 |
US |
Continuations (1)
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Number |
Date |
Country |
Parent |
09/408126 |
Sep 1999 |
US |
Child |
09/505716 |
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US |