Transplatin derivatives as anticancer agents

Patent metadata

Field	Value
Publication number	US-9974765-B1
Application number	US-201715715964-A
Country	US
Kind code	B1
Filing date	Sep 26, 2017
Priority date	Sep 26, 2017
Publication date	May 22, 2018
Grant date	May 22, 2018

Abstract

The invention is directed to platinum(II) thione complexes of formula (I) and to methods of treating cancer using these complexes.

First claim

The invention claimed is:

1. A method for inhibiting cell growth or proliferation comprising contacting a neoplastic eukaryotic cell with a platinum(II) thione complex represented by Formula (1):

wherein R 1 and R 2 are each, independently, a hydrogen or a C 1 -C 6 alkyl group, a is 1, 2 or 3; and X is nitrate, fluoride, chloride, bromide, iodide, or acetate.

2. The method of claim 1 that comprises administering trans-[Pt(NH 3 ) 2 (Imt) 2 ].2NO 3 (Complex 1), trans-[Pt(NH 3 ) 2 (MeImt) 2 ]. 2NO 3 (Complex 2), trans-[Pt(NH 3 ) 2 (Me 2 Imt) 2 ]. 2NO 3 (Complex 3), trans-[Pt(NH 3 ) 2 (Et 2 Imt) 2 ]. 2NO 3 (Complex 4), trans-[Pt(NH 3 ) 2 (PrImt) 2 ]. 2NO 3 (Complex 5), trans-[Pt(NH 3 ) 2 (iPrImt) 2 ]. 2NO 3 (Complex 6), or trans-[Pt(NH 3 ) 2 (iPr 2 Imt) 2 ].2 NO 3 (Complex 7).

3. The method of claim 1 that comprises administering trans-[Pt(NH 3 ) 2 (EtDiaz) 2 ]. 2NO 3 (Complex 8).

4. The method of claim 1 that comprises administering trans-[Pt(NH 3 ) 2 (Diap) 2 ]. 2NO 3 (Complex 9).

5. The method of claim 1 comprising administering the platinum(II) thione complex to a subject having breast cancer.

6. The method of claim 1 comprising administering the platinum(II) thione complex to a subject having lung cancer.

7. The method of claim 1 , wherein the platinum(II) thione complex is administered parenterally.

8. The method of claim 1 , wherein the pharmaceutical composition is administered intravenously.

9. The method of claim 1 , wherein the platinum(II) thione complex is administered into a tumor or into a site infiltrated by cancer cells.

10. The method of claim 1 , wherein the platinum(II) thione complex is administered along with a radiation treatment, surgical treatment, and/or another chemotherapeutic treatment.

11. A platinum(II) thione complex represented by Formula (1):

wherein R 1 and R 2 are each, independently, a hydrogen or a C 1 -C 6 alkyl group, a is 1, 2 or 3; and X is nitrate, fluoride, chloride, bromide, iodide, or acetate; with the proviso that when a is 2, then at least one of R 1 or R 2 is C 1 -C 6 alkyl.

12. The complex of claim 11 , wherein a is 1.

13. The complex of claim 11 , wherein a is 2.

14. The complex of claim 11 , wherein a is 3.

15. The complex of claim 11 that is trans-[Pt(NH 3 ) 2 (Imt) 2 ].2NO 3 (Complex 1), trans-[Pt(NH 3 ) 2 (MeImt) 2 ]. 2NO 3 (Complex 2), trans-[Pt(NH 3 ) 2 (Me 2 Imt) 2 ]. 2NO 3 (Complex 3), trans-[Pt(NH 3 ) 2 (Et 2 Imt) 2 ]. 2NO 3 (Complex 4), trans-[Pt(NH 3 ) 2 (PrImt) 2 ]. 2NO 3 (Complex 5), trans-[Pt(NH 3 ) 2 (iPrImt) 2 ]. 2NO 3 (Complex 6), trans-[Pt(NH 3 ) 2 (iPr 2 Imt) 2 ]. 2 NO 3 (Complex 7), trans-[Pt(NH 3 ) 2 (EtDiaz) 2 ]. 2NO 3 (Complex 8), or trans-[Pt(NH 3 ) 2 (Diap) 2 ]. 2NO 3 (Complex 9).

16. The complex of claim 11 that is trans-[Pt(NH 3 ) 2 (MeImt) 2 ]. 2NO 3 (Complex 2).

17. The complex of claim 11 that is trans-[Pt(NH 3 ) 2 (PrImt) 2 ]. 2NO 3 (Complex 5).

18. The complex of claim 11 that is trans-[Pt(NH 3 ) 2 (iPr 2 Imt) 2 ].2 NO 3 (Complex 7).

19. The complex of claim 11 that is trans-[Pt(NH 3 ) 2 (EtDiaz) 2 ]. 2NO 3 (Complex 8).

20. The complex of claim 11 that is trans-[Pt(NH 3 ) 2 (Diap) 2 ]. 2NO 3 (Complex 9).

Assignees

• Univ King Fahd Pet & Minerals

Inventors

• Jomaa Mohammed Y
• Altaf Muhammad
• Isab Anvarhusein A

Classifications

• A61K31/282 Primary

  Platinum compounds · CPC title

• C07F15/0093

  without a metal-carbon linkage · CPC title

• A61K31/4178

  not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin · CPC title