Monoimine ligand platinum analogs

Details Monoimine ligand platinum analogs Monoimine ligand platinum analogs

2007-09-11

2007-09-11

Nazario-Gonzalez, Porfirio (Department: 1621)

Organic compounds -- part of the class 532-570 series

Organic compounds

Heavy metal containing

C514S492000

Reexamination Certificate

active

11340806

ABSTRACT:
Disclosed herein are novel platinum-based analogs with a single substituted imine ligand: R7RC═NR8, wherein the R7RC═NR8functional group is covalently bonded to the platinum through nitrogen. The analogs also have nitrogen donor ligands capable of forming hydrogen bonds with the bases in DNA or RNA, and one or more leaving groups which can be displaced by water, hydroxide ions or other nucleophiles, which is thought to form active species in vivo, and then, form cross-linked complexes between nucleic acid strands, principally between purines in DNA (or RNA), i.e., at the Guanine or Adenine bases, thereof. These platinum analogs may also be more easily transported into tumor cells, due to their increased lipophilicity and are likely to be useful as anti-neoplastic agents, and in modulating or interfering with the synthesis or replication or transcription of DNA or translation or function of RNA in vitro or in vivo, as they are potentially capable of forming a platinum coordinate complex with a intact or nascent DNA or RNA and thereby interfering with cellular synthesis, transcription or replication of nucleic acid polynucleotides.

REFERENCES:
Intini et al., Journal of Biological Inorganic Chemistry, vol. 9, pp. 768-780 (2004).
Boccarelli et al., Journal of Medicinal Chemistry, vol. 49, No. 2, pp. 829-837 (2006).
Uchiyama, et al., The Isolation, “Characterization, and Isomerization of cis- and trans- Bis(benzonitrile)dichloroplatinum(II)”, Bull. Chem. Soc. Jpn., 54:181-85 (1981).

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