Compounds useful for the treatment of diseases associated with the formation of amyloid fibrils

1. A compound of structural formula (I):

in which

R 1 is a —NR a R b group, where R a and R b , independently, are a hydrogen atom or a C 1 -C 6 alkyl group; —OR C group, where R C is a hydrogen atom or a C 1 -C 6 alkyl group; a glycosyl; a C 1 -C 6 polyhydroxyalkyl; or a —NH—CH(R d )—COOR e group, where R d is a side chain of one of the 20 natural alpha-amino acids in either of their two enantiomerically pure forms L or D, and R e is a hydrogen atom or a C 1 -C 6 alkyl group; and

R 2 is a hydrogen atom, a C 1 -C 6 alkyl group, a glycosyl; a C 1 -C 6 polyhydroxyalkyl; —C(═O)—R f group, where R f is a C 1 -C 6 alkyl group; or a —CH 2 —COO—R g group, where R g is a hydrogen atom or a C 1 -C 6 alkyl group;

and pharmaceutically acceptable salts thereof.

2. A compound according to claim 1 , wherein R 1 is selected from: OH, NH 2 , OMe, OEt, or a CH(R d )—COR e group, where R d is the side chain of glycine, alanine, leucine, valine, aspartic acid or asparagine and where R e is H or a C 1 -C 6 alkyl group; and R 2 is selected from: H, Me, glycosyl, a —C(═O)—R f group, where R f is a Me, Et, t-Bu group; or a —CH 2 —COO—R g group, where R g is a hydrogen atom or a t-Bu group.

3. A compound according to claim 1 , selected from the group consisting of:

[1] 5-(2,4-difluorophenyl)-3-iodo-salicylic acid;

[2] ethyl 5-(2,4-difluorophenyl)-3-iodo-salicylate;

[3] methyl 5-(2,4-difluorophenyl)-3-iodo-salicylate;

[4] 5-(2,4-difluorophenyl)-3-iodo-salicylamide;

[5] tert-butyl [2-aminocarbonyl-4-(2,4-difluorophenyl)-6-iodo-phenoxy]-acetate;

[6] [2-aminocarbonyl-4-(2,4-difluorophenyl)-6-iodo-phenoxy]acetic acid;

[7] 5-(2,4-difluorophenyl)-3-iodo-salicylic acid 1-O-β-glycoside;

[8] ethyl 2′,4′-difluoro-4-methoxy-5-iodo-[1,1′]biphenyl-3-carboxylate;

[9] 2′,4′-difluoro-4-methoxy-5-iodo-[1,1′]biphenyl-3-carboxylic acid;

[10] ethyl 2′,4′-difluoro-4-acetyloxy-5-iodo-[1,1′]biphenyl-3-carboxylate;

[11] 2′,4′-difluoro-4-(t-butylcarbonyloxy)-5-iodo-[1,1′]biphenyl-3-carboxylic acid;

[12] 2′,4′-difluoro-4-(ethylcarbonyloxy)-5-iodo-[1,1′]biphenyl-3-carboxylic acid;

[13] ethyl ester of N-[5-(2,4-difluorophenyl)-3-iodo-salicyloyl]glycine;

[14] N-[5-(2,4-difluorophenyl)-3-iodo-salicyloyl]glycine;

[15] N-[5-(2,4-difluorophenyl)-3-iodo-salicyloyl]alanine;

[16] N-[5-(2,4-difluorophenyl)-3-iodo-salicyloyl]leucine;

[17] N-[5-(2,4-difluorophenyl)-3-iodo-salicyloyl]serine;

[18] N-[5-(2,4-difluorophenyl)-3-iodo-salicyloyl]valine;

[19] N-[5-(2,4-difluorophenyl)-3-iodo-salicyloyl]-aspartic acid and;

[20] N-[5-(2,4-difluorophenyl)-3-iodo-salicyloyl]asparagine.

4. A method for the preparation of a compound of formula (I) according to claim 1 , comprising a step of reacting diflunisal or at least one derivative thereof with an iodination reagent.

5. A method according to claim 4 , wherein the iodination reagent is selected from the group consisting of: elemental iodine; iodide salts; sodium iodide; potassium iodide; iodonium salts; iodine chloride; iodonium complexes; bis(pyridine)iodonium (I)tetrafluoroborate; bis(symcollidine)iodonium (I) hexafluorophosphate; organic iodine compounds; iodobenzene diacetate; and N-iodosuccinimde.

6. A pharmaceutical composition containing a compound according to claim 1 and one or more pharmaceutically acceptable excipients.