Benzylideneguanidine Derivatives and Therapeutic Use for the Treatment of Protein Misfolding Diseases

A method of treating a retinal disorder in a subject in need thereof, said method comprising administering to the subject a therapeutically effective amount of a compound of formula (II),

• or a pharmaceutically acceptable salt thereof, or a tautomeric form thereof wherein,
• R1 alkyl, Cl, F or Br;
• R2 is H or F;
• R3 is selected from H and alkyl;
• R4 is selected from H and C(O)R6;
• R5 is H;
• or R4 and R5 are linked to form a heterocyclic group which is optionally substituted with one or more R10 groups;
• R6 is selected from R7, OR7 and NR8R9;
• R7, R8 and R9 are each independently selected from alkyl, cycloalkyl, aralkyl, cycloalkenyl, heterocyclic, aryl and heteroaryl, each of which is optionally substituted with one or more R10 groups;
• each R10 is independently selected from halogen, OH, CN, NO2, COO-alkyl, aralkyl, SO2-alkyl, SO2-aryl, COOH, CO-alkyl, CO-aryl, NH2, NH-alkyl, N(alkyl)2, CF3, alkyl and alkoxy;
• X and Z are each independently CR11, and Y is N;
• and
• R11 is H or F.

A method of treating a retinal disorder in a subject in need thereof, said method comprising administering to the subject a therapeutically effective amount of a compound of formula (III),

• or a pharmaceutically acceptable salt thereof, or a tautomeric form thereof wherein,
• R1 is alkyl, Cl, F or Br;
• R2 is H or F;
• R3 is selected from H and alkyl;
• R4 is C(O)R6;
• R5 is H;
• or R4 and R5 are linked to form a heterocyclic group which is optionally substituted with one or more R10 groups;
• R6 is selected from R7, OR7 and NR8R9;
• R7, R8 and R9 are each independently selected from alkyl, cycloalkyl, aralkyl, cycloalkenyl, heterocyclic, aryl and heteroaryl, each of which is optionally substituted with one or more R10 groups;
• each R10 is independently selected from halogen, OH, CN, NO2, COO-alkyl, aralkyl, SO2-alkyl, SO2-aryl, COOH, CO-alkyl, CO-aryl, NH2, NH-alkyl, N(alkyl)2, CF3, alkyl and alkoxy;
• X and Z are each independently CR11, and Y is selected from CR11 and N;
• and
• R11 is H or F.

A method of treating a retinal disorder in a subject in need thereof, said method comprising administering to the subject a therapeutically effective amount of a compound of formula (IV),

• or a pharmaceutically acceptable salt thereof, or a tautomer thereof, wherein,
• R1 is alkyl or Br;
• R2 is H;
• R3 is selected from H and alkyl;
• R4 is selected from H and C(O)R6;
• R5 is H;
• or R4 and R5 are linked to form a heterocyclic group which is optionally substituted with one or more R10 groups;
• R6 is selected from OR7 and NR8R9;
• R7, R8 and R9 are each independently selected from alkyl, cycloalkyl, aralkyl, cycloalkenyl, heterocyclyl and aryl, each of which is optionally substituted with one or more R10 groups;
• each R10 is independently selected from halogen, OH, CN, NO2, COO-alkyl, aralkyl, SO2-alkyl, SO2-aryl, COOH, CO-alkyl, CO-aryl, NH2, NH-alkyl, N(alkyl)2, CF3, alkyl and alkoxy;
• X and Z are each CH and Y is CR11;
• R11 is H or F.