PT (IV) complexes containing 4,4′-disubstituted-2,2′-bipyridyl and their use in cancer therapy

Inventors

Bhowmik, Pradip K. • Spangelo, Bryan L. • Vo, Van • Han, Haesook • Tanthmanatham, Ontida

Abstract

Platinum-containing compounds for the treatment of disease, such as, for example, cancer, are provided herein. Specifically, platinum Pt(IV) complexes with a substituted 2,2′-bipyridine ring structure are provided, as are methods for using the complexes. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Core Innovation

The invention relates to platinum (Pt) complexes having a structure represented by a formula in which substituents X and chelating substituents A and B are varied within defined sets. Each X is independently selected from Br, Cl, or I, and each of A and B is independently selected from Br, Cl, I, OH, and OC(O)R3. The complexes further include defined substituent patterns for R3, R1/R2, and R4/R5 with integer ranges, and the document also addresses pharmaceutically acceptable derivatives.

The patent describes ligands comprising a 4,4′-bis(alkoxy/alkylthio)-2,2′-bipyridine structure, including 4,4′-bis(RO)-2,2′-bipyridine ligands and 4,4′-bis(RO2S)-2,2′-bipyridine ligands. The ligand structures are based on a 2,2′-bipyridine-4,4′-diol precursor and are functionalized by alkoxy/alkylthio substituent variation to obtain a family of related ligands with differing alkoxy/alkyl lengths.

The patent describes preparation of platinum complexes of the ligands, including Pt(II) complexes formed using Pt(DMSO)2Cl2 and Pt(IV) complexes having a structure represented as [PtCl2(OAc)2(4,4′-dialkoxy-2,2′-bipyridine)]. The patent reports characterization and evaluation outputs for the synthesized complexes, including yields, melting points, NMR, elemental analysis/DSC, and biological evaluation with trends in anti-proliferative activity and solubility improvements relative to cisplatin and Pt(II) precursors.

The claimed use of the defined Pt complex structures is directed to a method for treating cancer by administering a composition comprising a complex having a structure represented by the selected formula, or a pharmaceutically acceptable derivative thereof, in an effective amount to a subject having cancer. The patent text states that the treatment is for cancer in general and also lists broad cancer indications including breast cancer, lung cancer, prostate cancer, melanoma, leukemia, lymphoma, sarcoma, and solid tumors.

Claims Coverage

The independent claim coverage centers on a cancer-treatment method using an effective amount of a composition comprising a platinum complex defined by a selected formula. The inventive features are organized around the complex structure definition, including optional halogen and functional substituents, parameterized substituent patterns for R3, R1/R2, and R4/R5, and pharmaceutically acceptable derivatives.

Claim coverage is anchored by a cancer-treatment method that administers an effective amount of a composition containing a platinum complex defined by a selected formula. The main claim-defined inventive structure features are the optional halogen substituent X; optional A/B selections including OC(O)R3; and parameterized substituent architectures for R3, R1/R2, and R4/R5, with defined allowed ranges for integer parameters and pharmaceutically acceptable derivatives.

Stated Advantages

Documented Applications