Methods of treating amyloid disease using analogs of 1-(4-nitrophenyl) piperazine

A compound of Formula Ic, pharmaceutically acceptable salts, stereo-isomers, polymorphs, metabolites, analogues, pro-drugs and combinations:

• wherein R1 is selected from the group consisting of H, nitro, carboxylic acid, alkylcarboxylic acid, acetamide connected in either direction, N-(2-ethanol)amine, N-(2-morpholmethyl)amine, amine optionally substituted with one or more alkyl groups, amide optionally substituted with one or more alkyl groups, and alkoxy;
• R2 is selected from the group consisting of H, carboxylic acid, alkyl, alkanoyl, alkanesulfonyl, benzenesulfonyl;
• phenonyl optionally substituted with any one or more of alkoxy, halogen, or alkyl groups, benzyl optionally substituted with any one or more of alkoxy, halogen, or alkyl groups, and amide optionally substituted with any one or more of alkyl or aryl groups;
• R3 is selected from the group consisting of H, alkyl, furanoalkyl, thiophenealkyl, alkanoyl, phenyl optionally substituted with any one or more halogen, alkyl, or alkoxy groups, benzyl optionally substituted with any one or more halogen, alkyl, or alkoxy groups, and phenonyl optionally substituted with any one or more halogen, alkyl, or alkoxy groups;
• and R4 is selected from the group consisting of H, alkyl, or phenyl optionally substituted with any one or more halogen, alkyl, or alkoxy groups.

A method of treating amyloid diseases, comprising administering to a human a compound of formula Ic, pharmaceutically acceptable salts, stereo-isomers, polymorphs, metabolites, analogues, pro-drugs and combinations:

• wherein R1 is selected from the group consisting of H, nitro, carboxylic acid, alkylcarboxylic acid, acetamide connected in either direction, N-(2-ethanol)amine, N-(2-morpholmethyl)amine, amine optionally substituted with one or more alkyl groups, amide optionally substituted with one or more alkyl groups, and alkoxy;
• R2 is selected from the group consisting of H, carboxylic acid, alkyl, alkanoyl, alkanesulfonyl, benzenesulfonyl, phenonyl optionally substituted with any one or more of alkoxy, halogen, or alkyl groups, benzyl optionally substituted with any one or more of alkoxy, halogen, or alkyl groups, and amide optionally substituted with any one or more of alkyl or aryl groups;
• R3 is selected from the group consisting of H, alkyl, furanoalkyl, thiophenealkyl, alkanoyl, phenyl optionally substituted with any one or more halogen, alkyl, or alkoxy groups, benzyl optionally substituted with any one or more halogen, alkyl, or alkoxy groups, and phenonyl optionally substituted with any one or more halogen, alkyl, or alkoxy groups;
• and R4 is selected from the group consisting of H, alkyl, or phenyl optionally substituted with any one or more halogen, alkyl, or alkoxy groups, in the manufacture of a dosage form for the treatment of amyloid diseases.

A pharmaceutical composition, comprising a therapeutically effective amount of a compound of Formula Ic, pharmaceutically acceptable salts, stereo-isomers, polymorphs, metabolites, analogues, pro-drugs and combinations:

• wherein R1 is selected from the group consisting of H, nitro, carboxylic acid, alkylcarboxylic acid, acetamide connected in either direction, N-(2-ethanol)amine, N-(2-morpholmethyl)amine, amine optionally substituted with one or more alkyl groups, amide optionally substituted with one or more alkyl groups, and alkoxy;
• R2 is selected from the group consisting of H, carboxylic acid, alkyl, alkanoyl, alkanesulfonyl, benzenesulfonyl, phenonyl optionally substituted with any one or more of alkoxy, halogen, or alkyl groups, benzyl optionally substituted with any one or more of alkoxy, halogen, or alkyl groups, and amide optionally substituted with any one or more of alkyl or aryl groups;
• R3 is selected from the group consisting of H, alkyl, furanoalkyl, thiophenealkyl, alkanoyl, phenyl optionally substituted with any one or more halogen, alkyl, or alkoxy groups, benzyl optionally substituted with any one or more halogen, alkyl, or alkoxy groups, and phenonyl optionally substituted with any one or more halogen, alkyl, or alkoxy groups;
• and R4 is selected from the group consisting of H, alkyl, or phenyl optionally substituted with any one or more halogen, alkyl, or alkoxy groups.