Methods for suppressing accumulation of reflux-induced protein adducts

A method for ameliorating the risk of esophageal adenocarcinoma for a subject in need thereof, comprising administering to the subject a compound of the following formula:

• wherein:
• R is C;
• R2 is independently H, hydroxy, halogen, nitro, CF3, C1-6 alkyl, C1-6 alkoxy, C3-10 cycloalkyl, C3-8 membered ring containing C, O, S or N, optionally substituted with one or more R2, R3 and R4, and may cyclize with to one or more R2, R3, or R5 to form an optionally substituted C3-8 membered ring containing C, O, S or N;
• R3 is H, hydroxy, halogen, nitro, CF3, C1-6 alkyl, C1-6 alkoxy, C3-10 cycloalkyl, C3-8 membered ring containing C, O, S or N, optionally substituted with one or more R4, R2 and R3 may cyclize with to one or more R2 or R5 to form an optionally substituted C3-8 membered ring containing C, O, S or N;
• R4 is H, hydroxy, halogen, nitro, CF3, C1-6 alkyl, C1-6 alkoxy, C3-10 cycloalkyl, C3-8 membered ring containing C, O, S or N, optionally substituted with one or more R4, R2 and R3 may cyclize with to one or more R2, R3, or R5 to form an optionally substituted C3-8 membered ring containing C, O, S or N;
• R5 is a bond, H, hydroxy, halogen, nitro, CF3, C1-6 alkyl, C1-6 alkoxy, C3-10 cycloalkyl, C3-8 membered ring containing C, O, S or N, optionally substituted with one or more R4, R2 and R3 may cyclize with to one or more R2, R3, or R4 to form an optionally substituted C3-8 membered ring containing C, O, S or N;
• and stereoisomers and analogs thereof;
• and pharmaceutically acceptable salts thereof.

A method of reducing or ameliorating reactive oxygen species produced by reflux for a subject in need thereof, comprising administering to a subject in need thereof a compound of the following formula:

• wherein:
• R is C;
• R2 is independently H, hydroxy, halogen, nitro, CF3, C1-6 alkyl, C1-6 alkoxy, C3-10 cycloalkyl, C3-8 membered ring containing C, O, S or N, optionally substituted with one or more R2, R3 and R4, and may cyclize with to one or more R2, R3, or R5 to form an optionally substituted C3-8 membered ring containing C, O, S or N;
• R3 is H, hydroxy, halogen, nitro, CF3, C1-6 alkyl, C1-6 alkoxy, C3-10 cycloalkyl, C3-8 membered ring containing C, O, S or N, optionally substituted with one or more R4, R2 and R3 may cyclize with to one or more R2 or R5 to form an optionally substituted C3-8 membered ring containing C, O, S or N;
• R4 is H, hydroxy, halogen, nitro, CF3, C1-6 alkyl, C1-6 alkoxy, C3-10 cycloalkyl, C3-8 membered ring containing C, O, S or N, optionally substituted with one or more R4, R2 and R3 may cyclize with to one or more R2, R3, or R5 to form an optionally substituted C3-8 membered ring containing C, O, S or N;
• R5 is a bond, H, hydroxy, halogen, nitro, CF3, C1-6 alkyl, C1-6 alkoxy, C3-10 cycloalkyl, C3-8 membered ring containing C, O, S or N, optionally substituted with one or more R4, R2 and R3 may cyclize with to one or more R2, R3, or R4 to form an optionally substituted C3-8 membered ring containing C, O, S or N;
• and stereoisomers and analogs thereof;
• and pharmaceutically acceptable salts thereof.

A method for treating, preventing, or ameliorating esophageal damage caused by reflux, comprising the step of co-administering to the subject at least one compound of the following formula:

• wherein:
• R is C;
• R2 is independently H, hydroxy, halogen, nitro, CF3, C1-6 alkyl, C1-6 alkoxy, C3-10 cycloalkyl, C3-8 membered ring containing C, O, S or N, optionally substituted with one or more R2, R3 and R4, and may cyclize with to one or more R2, R3, or R5 to form an optionally substituted C3-8 membered ring containing C, O, S or N;
• R3 is H, hydroxy, halogen, nitro, CF3, C1-6 alkyl, C1-6 alkoxy, C3-10 cycloalkyl, C3-8 membered ring containing C, O, S or N, optionally substituted with one or more R4, R2 and R3 may cyclize with to one or more R2 or R5 to form an optionally substituted C3-8 membered ring containing C, O, S or N;
• R4 is H, hydroxy, halogen, nitro, CF3, C1-6 alkyl, C1-6 alkoxy, C3-10 cycloalkyl, C3-8 membered ring containing C, O, S or N, optionally substituted with one or more R4, R2 and R3 may cyclize with to one or more R2, R3, or R5 to form an optionally substituted C3-8 membered ring containing C, O, S or N;
• R5 is a bond, H, hydroxy, halogen, nitro, CF3, C1-6 alkyl, C1-6 alkoxy, C3-10 cycloalkyl, C3-8 membered ring containing C, O, S or N, optionally substituted with one or more R4, R2 and R3 may cyclize with to one or more R2, R3, or R4 to form an optionally substituted C3-8 membered ring containing C, O, S or N;
• and stereoisomers and analogs thereof, with a drug having a known side effect of treating, preventing, or ameliorating reflux.