Inhibitors of heat shock factors and uses thereof

An HSF inhibitor, wherein the inhibitor is an acrylamide derivative of

• (a) formula (II)
• or a salt thereof, wherein
• Z1 is a 5-8 membered, non-aromatic heterocycle,
• n is 0-8 (or 0-6 if Z1 is a 5-membered heterocycle);
• X1 is N or C(—R1);
• X2 is C(—R2), N, or S or O (double bond between X3 and X4 instead of between X2 and X3);
• X3 is C(—R) or N;
• X4 is S or O, or C(—R4) or N if X2 is O or S (double bond between X3 and X4 instead of between X2 and X3),
• X6 is O, S, N, NH, (C1-C4)alkylN, CH or C((C1-C4)alkyl), CH2 or CH((C1-C4)alkyl);
• R1 is H, halo, (C1-C4)alkyl or halo(C1-C4)alkyl;
• R2, R3, R5 and R8 are independently selected, and each can be H or any substituent, provided that its presence is compatible with the small molecule nature of the inhibitor and, statistically, no more than 10% of any ionizable group it may contain is ionized at neutral pH;
• whereby R2 and R3 can form a substituted or unsubstituted 5 to 8 membered aromatic or non-aromatic ring or heterocycle including X2 and X3;
• R4 is H, halo, (C1-C4)alkyl or halo(C1-C4)alkyl,
• (b) formula (V),
• or a salt thereof, whereby R2 and R5 are independently selected, and each can be any substituent, provided that its presence is compatible with the small molecule nature of the inhibitor and, statistically, no more than 10% of any ionizable group it may contain is ionized at neutral pH;
• X5 is O, S or N(—R6);
• R6 is H or is selected from halogen, OH, SH, NH2 and Z2 whereby Z2 is a residue comprising from 1 to 4 carbon atoms;
• R7 is —O—Z2, —S—Z2, —NH—Z2 or —N—(Z2)2;
• X7 is CH or N (with 3 or less of the X7 being N);
• R10 is defined as R5;
• and s is 0, 1, 2, 3 or 4, with the proviso that the inhibitor in which both R2 and R5 are H, s is 0, R7 is ethoxy, X5 is O and all X7 are CH is excluded,
• (c) formula (IX)
• or a salt thereof, whereby R5 can be any substituent, provided that its presence is compatible with the small molecule nature of the inhibitor and, statistically, no more than 10% of any ionizable group it may contain is ionized at neutral pH;
• X5 is O, S or N(—R6);
• R6 is H or is selected from halogen, OH, SH, NH2 and Z2 whereby Z2 is a residue comprising from 1 to 4 carbon atoms;
• R7 is —O—Z2, —S—Z2, —NH—Z2 or —N—(Z2)2;
• r is 0-4 and R11 is defined as R5, with the proviso that, if r is 0, R5, R7 and X5 cannot be simultaneously H, methoxy and O, respectively, or
• (d) formula (X)
• or a salt thereof, whereby Z1 is a 5-8 membered, non-aromatic heterocycle;
• n is 0-8 (or 0-6 if Z1 is a 5-membered heterocycle);
• X6 is O, S, N, NH, (C1-C4)alkylN, CH or C((C1-C4)alkyl), CH2 or CH((C1-C4)alkyl), R5 and R8 are independently selected, and each can be any substituent, provided that its presence is compatible with the small molecule nature of the inhibitor and, statistically, no more than 10% of any ionizable group it may contain is ionized at neutral pH;
• r is 0-4 and R11 is defined as R5.