Platinum-containing compounds exhibiting cytostatic activity, synthesis and methods of use

1. A compound of Formula (I):

or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of any of the foregoing, wherein:

n is an integer from 0 to 4;

p is chosen from 0 and 1;

L 1 and L 2 are each NH 3 or L 1 and L 2 together form a 1,2-cycloalkanediamine chosen from trans-(1R,2R)-cyclohexanediamine, trans-(1S,2S)-cyclohexanediamine, and cis-(R,S)-cyclohexanediamine;

R 1 is chosen from hydrogen and C 1-4 alkyl;

each R 2 is independently chosen from hydrogen and C 1-4 alkyl;

Y is chosen from —NR 5 — and —O—;

R 3 is chosen from

wherein R 6 is chosen from hydrogen and C 1-4 alkyl; and

R 5 is chosen from hydrogen and C 1-4 alkyl.

2. The compound of claim 1 , wherein R 1 is hydrogen.

3. The compound of claim 1 , wherein each R 2 is hydrogen.

4. The compound of claim 1 , wherein n is chosen from 1 and 2.

5. The compound of claim 1 , wherein Y is chosen from —NH— and —O—.

6. The compound of claim 1 , wherein R 6 is chosen from hydrogen and methyl.

7. The compound of claim 1 , wherein L 1 and L 2 are each NH 3 or L 1 and L 2 together are trans-(1R,2R)-cyclohexanediamine.

8. The compound of claim 1 , wherein L 1 and L 2 together are trans-(1R,2R)-cyclohexanediamine.

9. The compound of claim 1 , wherein R 1 is hydrogen and each R 2 is hydrogen.

10. The compound of claim 1 , wherein R 1 is hydrogen, each R 2 is hydrogen, and n is chosen from 1 and 2.

11. The compound of claim 1 , wherein R 1 is hydrogen, each R 2 is hydrogen, and Y is —NH—.

12. The compound of claim 1 , wherein R 1 is hydrogen, each R 2 is hydrogen, n is chosen from 1 and 2, and Y is —NH—.

13. The compound of claim 1 , wherein R 1 is hydrogen, each R 2 is hydrogen, n is chosen from 1 and 2, and Y is —O—.

14. A compound of Formula (X):

or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of any of the foregoing, wherein:

n is chosen from 1 and 2;

p is chosen from 0 and 1;

L 1 and L 2 are each NH 3 or L 1 and L 2 together are trans-(1R,2R)-cyclohexanediamine;

Y is chosen from —NH— and —O—; and

R 3 is chosen from

wherein R 6 is chosen from hydrogen and methyl.

15. The compound of claim 14 , wherein Y is —NH—.

16. The compound of claim 14 , wherein Y is —O—.

17. A compound chosen from:

[1R,2R-Cyclohexanediamine-N,N′][{2-(β-D-Glucopyranos-1-ylamido)ethyl}propanedioato(2-)-O,O′]Platinum(II);

[1R,2R-Cyclohexanediamine-N,N′][{2-(β-D-Galactopyranos-1-ylamido)ethyl}propanedioato(2-)-O,O′]Platinum (II);

[1R,2R-Cyclohexanediamine-N,N′][{2-(β-D-Mannopyranos-1-ylamido)ethyl}propanedioato(2-)-O,O′]Platinum(II);

[1R,2R-Cyclohexanediamine-N,N′][{3-(β-D-Glucopyranos-1-ylamido)propyl}propanedioato(2-)-O,O′]Platinum(II);

[1R,2R-Cyclohexanediamine-N,N′][{3-(β-D-Galactopyranos-1-ylamido)propyl}propanedioato(2-)-O,O′]Platinum(II);

[1R,2R-Cyclohexanediamine-N,N′] [{3-(α,β-D-Galactopyranos-6-ylamido)propyl}propanedioato(2-)-O,O′]Platinum(II);

[Diammine][{3-(α,β-D-Galactopyranos-6-ylamido)propyl}propanedioato(2-)-O,O′]Platinum(II);

[1R,2R-Cyclohexanediamine-N,N′][{3-(α,β-D-Mannopyranos-6-ylamido)propyl}propanedioato(2-)-O,O′]Platinum(II);

[1R,2R-Cyclohexanediamine-N,N′][{3-(α,β-D-Glucopyranos-6-ylamido)propyl}propanedioato(2-)-O,O′]Platinum(II);

[1R,2R-Cyclohexanediamine-N,N′][{3-(Methyl-α-D-Glucopyranos-6-ylamido)propyl}propanedioato(2-)-O,O′]Platinum(II);

[1R,2R-Cyclohexanediamine-N,N′][{2-(Methyl-α-D-Glucopyranos-6-yl-carbonyl)ethyl}propanedioato(2-)-O,O′]Platinum(II);

[1R,2R-Cyclohexanediamine-N,N′][{2-(Methyl-α-D-Mannopyranos-6-yl-carbonyl)ethyl}propanedioato(2-)-O,O′]Platinum(II);

[1R,2R-Cyclohexanediamine-N,N′][{2-(α,β-D-Glucopyranos-1-yl)ethyl}propanedioato(2-)-O,O′]Platinum(II);

[1R,2R-Cyclohexanediamine-N,N′][{2-(α,β-D-Galactopyranos-1-yl)ethyl}propanedioato(2-)-O,O′]Platinum(II);

[1R,2R-Cyclohexanediamine-N,N′][{2-(α,β-D-Glucuron-6-yl-amido)ethyl}propanedioato(2-)-O,O′]Platinum(II);

[1R,2R-Cyclohexanediamine-N,N′][{2-(α,β-D-Galacturon-6-yl-amido)ethyl}propanedioato(2-)-O,O′]Platinum(II);

[1R,2R-Cyclohexanediamine-N,N′][{2-(Methyl-β-D-Glucuron-6-yl-amido)ethyl}propanedioato(2-)-O,O′]Platinum(II); and

[1R,2R-Cyclohexanediamine-N,N′][{3-(α,β-D-Mannopyranos-1-yl)propyl}propanedioato(2-)-O,O′]Platinum (II);

or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvates of any of the foregoing.

18. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable vehicle.

19. The pharmaceutical composition of claim 18 , wherein the compound is present in an amount effective for treating cancer in a patient.

20. A method of treating cancer in a patient comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound of claim 1 .

21. A method of treating cancer in a patient comprising administering to a patient in need of such treatment a therapeutically effective amount of a pharmaceutical composition of claim 18 .

22. A compound of Formula (XI):

or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of any of the foregoing, wherein:

L 1 and L 2 are each NH 3 or L 1 and L 2 together form a 1,2-cycloalkanediamine chosen from trans-(1R,2R)-cyclohexanediamine, trans-(1S,2S)-cyclohexanediamine, and cis-(R,S)-cyclohexanediamine; and

R 3 is

23. The compound of claim 22 , wherein L 1 and L 2 are each NH 3 or L 1 and L 2 together are trans-(1R,2R) cyclohexanediamine.

24. A compound chosen from:

[1R,2R-Cyclohexanediamine-N,N′][{3-(α,β-D-Glucopyranos-2-yl-amido)propyl}propanedioato(2-)-O,O′]Platinum(II); and

[Diammine][{3-(α,β-D-Glucopyranos-2-yl-amido)propyl}propanedioato(2-)-O,O′]Platinum(II);

or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of any of the foregoing.