Boronated metal-phthalocyanines, process for their preparation, pharmaceutical compositions comprising them and use thereof

1. A compound of formula (I)

in which

M is selected from the group consisting of Si, Al and Ge,

q is 0 or 1,

R is a group G-(Q) m -((X) l —((Y) k —Z) n ) t wherein

G is selected from the group consisting of O and O—Si(CH 3 ) 2 ,

Q is selected from the group consisting of T, Ph, CH 2 -Ph, and triazine, wherein T is selected from the group consisting of

and —(CH 2 ) v —, and v is an integer comprised between 1 and 5,

X is selected from the group consisting of O, S, T, O-T, S-T, T-O-T, T-S-T, Ph, and O-Ph, wherein T is as defined above,

Y is selected from the group consisting of —(CH 2 ) v —, O—(CH 2 ) v —, —(CH 2 ) v —O—(CH 2 ) v —, phenyl, O-Ph, Ph-CH 2 , O-Ph-CH 2 and

wherein v is as defined above,

Z is a 10 B or 11 B boron cluster selected from the group consisting of o,m,p-carboranyl, undecahydro-closo-dodecaboranyl, 1-methyl-o,m,p-carboranyl, undecahydro-closo-dodecaboromercaptyl, nido-7,8-carboranyl, nido-7,9-carboranyl, nido-7,8-methylcarboranyl and bis-p-carboranyl,

m is 0 or 1,

l is an integer comprised between 0 and 3,

k is 0 or 1,

n is an integer comprised between 1 and 3,

t is an integer comprised between 1 and 3,

R 1 is selected from the group consisting of R, CH 3 , OH, O-glucide,

(OCH 2 CH 2 ) s —OR 4 , and polypeptide, wherein R is as defined above, R 4 is selected from the group consisting of H, methyl, and ethyl, and s is an integer comprised between 1 and 10,

R 2 is selected from the group consisting of H and (W) p —(OCH 2 CH 2 ) v —OR 4 , wherein W is selected from the group consisting of S—(CH 2 ) v , and OPh, p is 0 or 1, v and R 4 are as defined above, and

R 3 is selected from the group consisting of H and R 2 ,

or, when R 2 and R 3 are in the positions 2,3,9,10,16,17,23,24, R 2 and R 3 , taken together, are a condensed aromatic nucleus;

provided that:

R 2 and R 3 are in the positions 1,4,8,11,15,18,22,25 or 2,3,9,10,16,17,23,24,

when M is Si or Ge, q is 1, and when M is Al, q is 0,

or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , wherein Z is a 10 B boron cluster.

3. The compound according to claim 1 , wherein Z is a 11 B boron cluster.

4. The compound according to claim 1 , wherein M is Si.

5. The compound according to claim 1 , wherein m is 1, t is 1 and 1 is 0.

6. The compound according to claim 1 , wherein said glucide is a residue of mono- or di-saccharides.

7. The compound according to claim 6 , wherein said glucide is selected from the group consisting of glucose, galactose, and lactose.

8. The compound according to claim 1 , wherein said O-glucide is O-glucose.

9. The compound according to claim 1 , wherein the group Z is a 10 B or 11 B boron cluster selected from the group consisting of o-carboranyl, 1-methyl-o-carboranyl, nido-7,8-carboranyl, and nido-7,8-methylcarboranyl.

10. The compound according to claim 9 , wherein the group Z is a 10 B or 11 B boron cluster selected from the group consisting of o-carboranyl, and 1-methyl-o-carboranyl.

11. The compound according to claim 1 , wherein the group Q is selected from the group consisting of Ph, triazine, CH 2 Ph, CH 2 ,

and the group Y is selected from the group consisting of CH 2 , OCH 2 , and CH 2 —O—CH 2 .

12. The compound according to claim 1 , wherein the condensed aromatic nucleus is a benzene ring condensed with the benzene ring of the phthalocyanine nucleus, so to form a naphthalocyanine nucleus.

13. The compound according to claim 1 , selected from the following compounds:

bis(3-o-carboranylpropyl-1-oxy) silicon phthalocyanine

{bis[3,5-bis(o-carboranylmethyloxy)-1-phenoxy]} silicon phthalocyanine

{[3,5-bis(o-carboranylmethyloxy)-1-phenoxy]methyl} silicon phthalocyanine

{bis[3,5-di(o-carboranylmethyloxy)-1-phenoxy]-1,4,8,11,15,18,22,25-octa[2-(2-ethoxy ethoxy)ethoxy]} silicon phthalocyanine

{bis[3,5-di-(m-carboranylmethyl)-2,4,6-triazin-1-yloxy]} silicon phthalocyanine

{[3,5-bis(m-carboranylmethyl)-2,4,6-triazin-1-yloxy]methyl} silicon phthalocyanine

{bis[1,3-bis(o-methylcarboranylmethyloxy)-propyl-2-oxy]} silicon phthalocyanine

{bis{3,5-bis[3,5-di(o-methylcarboranylmethyl)-1-phenoxy]-1-phenoxy}} silicon phthalocyanine

{[1,3-bis(p-carboranyl)-propyl-2-oxy]methyl} silicon phthalocyanine

{[3,5-bis( 10 B-o-carboranylmethyloxy)-1-phenoxy]hydroxy} silicon phthalocyanine

{[3,5-bis( 10 B-o-carboranylmethyloxy)-1-phenoxy] 6-O-α-D-glucopyranosyl} silicon phthalocyanine

{[3,5-bis( 10 B-o-carboranylmethyloxy)-1-phenoxy]} {[2-(2-ethoxyethoxy)ethoxy]} silicon phthalocyanine

{bis[3,5-bis( 10 B-o-carboranylmethyloxy)-1-phenoxy]} silicon phthalocyanine

{bis[3,5-bis((2-methyl- 10 B-carboran-1-methyloxy)-1-phenoxyl]}silicon phthalo cyanine

{bis[3,5-bis((2-methyl- 10 B-carboran-1-yl)methyloxy)-1-phenoxy]-1,4,8,11,15,18, 22,25-octa((2-ethoxyethoxy)ethoxy)} silicon phthalocyanine

{bis[3,5-bis( 10 B-o-carboranylmethyloxy)-1-phenoxy] 1,4,8,11,15,18,22,25-octa[(2-ethoxyethoxy)ethoxy]} silicon phthalocyanine

{bis(3- 10 B-o-carboranylpropyl-1-oxy)} silicon phthalocyanine

{bis[3-(2-methyl- 10 B-carboran-1-yl)propyl-1-oxy]} silicon phthalocyanine

{bis[3- 10 B-o-carboranylpropyl-1-oxy]-1,4,8,11,15,18,22,25-octa[(2-ethoxy ethoxy)ethoxy]} silicon phthalocyanine

bis(3-o-carboranylpropyl-1-oxy) silicon naphthalocyanine

bis(3- 10 B-o-carboranylpropyl-1-oxy) silicon naphthalocyanine

{bis[3-(2-methyl- 10 B-carboran-1-yl)propyl-1-oxy]} silicon naphthalocyanine.

14. A pharmaceutical composition containing at least one compound of claim 1 , or a pharmaceutically acceptable salt thereof.

15. A pharmaceutical composition containing at least one compounds of claim 2 , or a pharmaceutically acceptable salt thereof.

16. A diagnostic agent containing at least one compound of claim 1 , or a pharmaceutically acceptable salt thereof.

17. A diagnostic method ex vivo/in vivo employing at least one compound of claim 1 , or a pharmaceutically acceptable salt thereof.

18. A method for the treatment of a patient suffering from pigmented melanoma tumours, by BNCT therapy, or PDT therapy applied individually, sequentially, or in combination wherein compounds as defined in claim 1 are administered to the patient.