Bis(thio-hydrazide amides) for treatment of hyperplasia

A method of treating a proliferative vascular disorder in a subject, comprising administering to the subject an effective amount of a compound represented by the following Structural Formula:

• or a pharmaceutically acceptable salt or solvate thereof, wherein:
• R7-R8 are both —H, and:
• R1 and R2 are both phenyl, R3 and R4 are both methyl, and R5 and R6 are both —H;
• R1 and R2 are both phenyl, R3 and R4 are both ethyl, and R5 and R6 are both —H;
• R1 and R2 are both 4-cyanophenyl, R3 and R4 are both methyl, R5 is methyl, and R6 is —H;
• R1 and R2 are both 4-methoxyphenyl, R3 and R4 are both methyl, and R5 and R6 are both —H;
• R1 and R2 are both phenyl, R3 and R4 are both methyl, R5 is methyl, and R6 is —H;
• R1 and R2 are both phenyl, R3 and R4 are both ethyl, R5 is methyl, and R6 is —H;
• R1 and R2 are both 4-cyanophenyl, R3 and R4 are both methyl, and R5 and R6 are both —H;
• R1 and R2 are both 2,5-dimethoxyphenyl, R3 and R4 are both methyl, and R5 and R6 are both —H;
• R1 and R2 are both 2,5-dimethoxyphenyl, R3 and R4 are both methyl, R5 is methyl, and R6 is —H;
• R1 and R2 are both 3-cyanophenyl, R3 and R4 are both methyl, and R5 and R6 are both —H;
• R1 and R2 are both 3-fluorophenyl, R3 and R4 are both methyl, and R5 and R6 are both —H;
• R1 and R2 are both 4-chlorophenyl, R3 and R4 are both methyl, R5 is methyl, and R6 is —H;
• R1 and R2 are both 2-dimethoxyphenyl, R3 and R4 are both methyl, and R5 and R6 are both —H;
• R1 and R2 are both 3-methoxyphenyl, R3 and R4 are both methyl, and R5 and R6 are both —H;
• R1 and R2 are both 2,3-dimethoxyphenyl, R3 and R4 are both methyl, and R5 and R6 are both —H;
• R1 and R2 are both 2,3-dimethoxyphenyl, R3 and R4 are both methyl, R5 is methyl, and R6 is —H;
• R1 and R2 are both 2,5-difluorophenyl, R3 and R4 are both methyl, and R5 and R6 are both —H;
• R1 and R2 are both 2,5-difluorophenyl, R3 and R4 are both methyl, R5 is methyl, and R6 is —H;
• R1 and R2 are both 2,5-dichlorophenyl, R3 and R4 are both methyl, and R5 and R6 are both —H;
• R1 and R2 are both 2,5-dimethylphenyl, R3 and R4 are both methyl, and R5 and R6 are both —H;
• R1 and R2 are both 2,5-dimethoxyphenyl, R3 and R4 are both methyl, and R5 and R6 are both —H;
• R1 and R2 are both phenyl, R3 and R4 are both methyl, and R5 and R6 are both —H;
• R1 and R2 are both 2,5-dimethoxyphenyl, R3 and R4 are both methyl, R5 is methyl, and R6 is —H;
• R1 and R2 are both cyclopropyl, R3 and R4 are both methyl, and R5 and R6 are both —H;
• R1 and R2 are both cyclopropyl, R3 and R4 are both ethyl, and R5 and R6 are both —H;
• R1 and R2 are both cyclopropyl, R3 and R4 are both methyl, R5 is methyl, and R6 is —H;
• R1 and R2 are both 1-methylcyclopropyl, R3 and R4 are both methyl, and R5 and R6 are both —H;
• R1 and R2 are both 1-methylcyclopropyl, R3 and R4 are both methyl, R5 is methyl and R6 is —H;
• R1 and R2 are both 1-methylcyclopropyl, R3 and R4 are both methyl, R5 is ethyl, and R6 is —H;
• R1 and R2 are both 1-methylcyclopropyl, R3 and R4 are both methyl, R5 is n-propyl, and R6 is —H;
• R1 and R2 are both 1-methylcyclopropyl, R3 and R4 are both methyl, and R5 and R6 are both methyl;
• R1 and R2 are both 1-methylcyclopropyl, R3 and R4 are both ethyl, and R5 and R6 are both —H;
• R1 and R2 are both 1-methylcyclopropyl, R3 is methyl, R4 is ethyl, and R5 and R6 are both —H;
• R1 and R2 are both 2-methylcyclopropyl, R3 and R4 are both methyl, and R5 and R6 are both —H;
• R1 and R2 are both 2-phenylcyclopropyl, R3 and R4 are both methyl, and R5 and R6 are both —H;
• R1 and R2 are both 1-phenylcyclopropyl, R3 and R4 are both methyl, and R5 and R6 are both —H;
• R1 and R2 are both cyclobutyl, R3 and R4 are both methyl, and R5 and R6 are both —H;
• R1 and R2 are both cyclopentyl, R3 and R4 are both methyl, and R5 and R6 are both —H;
• R1 and R2 are both cyclohexyl, R3 and R4 are both methyl, and R5 and R6 are both —H;
• R1 and R2 are both cyclohexyl, R3 and R4 are both phenyl, and R5 and R6 are both —H;
• R1 and R2 are both methyl, R3 and R4 are both methyl, and R5 and R6 are both —H;
• R1 and R2 are both methyl, R3 and R4 are both t-butyl, and R5 and R6 are both —H;
• R1 and R2 are both methyl, R3 and R4 are both phenyl, and R5 and R6 are both —H;
• R1 and R2 are both t-butyl, R3 and R4 are both methyl, and R5 and R6 are both —H;
• R1 and R2 are ethyl, R3 and R4 are both methyl, and R5 and R6 are both —H;
• or
• R1 and R2 are both n-propyl, R3 and R4 are both methyl, and R5 and R6 are both —H.

A medical device comprising a reservoir, a coating composition or a controlled release polymer matrix that comprises a compound represented by the following Structural Formula:

• or a pharmaceutically acceptable salt or solvate thereof, wherein:
• Y is a covalent bond or an optionally substituted straight chained hydrocarbyl group, or, Y, taken together with both >C=Z groups to which it is bonded, is an optionally substituted aromatic group;
• R1 -R4 are independently —H, an optionally substituted aliphatic group, an optionally substituted aryl group, or R1 and R3 taken together with the carbon and nitrogen atoms to which they are bonded, and/or R2 and R4 taken together with the carbon and nitrogen atoms to which they are bonded, form a non-aromatic heterocyclic ring optionally fused to an aromatic ring;
• R7-R8 are independently —H, an optionally substituted aliphatic group, or an optionally substituted aryl group;
• and
• Z is O or S,
• wherein the compound is released in vivo.

A method of treating a proliferative cell disorder at a treatment site in a subject, comprising contacting the subject with a medical device that comprises a reservoir, a coating composition or a controlled release polymer matrix comprises a compound represented by the following Structural Formula:

• or a pharmaceutically acceptable salt or solvate thereof, wherein:
• Y is a covalent bond or an optionally substituted straight chained hydrocarbyl group, or, Y, taken together with both >C=Z groups to which it is bonded, is an optionally substituted aromatic group;
• R1-R4 are independently —H, an optionally substituted aliphatic group, an optionally substituted aryl group, or R1 and R3 taken together with the carbon and nitrogen atoms to which they are bonded, and/or R2 and R4 taken together with the carbon and nitrogen atoms to which they are bonded, form a non-aromatic heterocyclic ring optionally fused to an aromatic ring;
• R7-R8 are independently —H, an optionally substituted aliphatic group, or an optionally substituted aryl group;
• and
• Z is O or S;
• and
• releasing the compound in vivo.