A Novel Approach to Preparing Water Soluble Prodrug Forms of Cisplatin Analogues Bearing Chelating Diamines

Köckerbauer, Reinhold; Bednarski, Patrick J.

doi:10.1002/jps.2600840707

Cited by 5 publications

(3 citation statements)

References 12 publications

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“…An unusual water-soluble platinum compound can be prepared in a chelate-opened zwitterionic form under acidic conditions. At physiological pH, the diamine chelate closes, forming a conventional platinum compound that has in vivo activity …”

Section: 7 Water-soluble Complexesmentioning

confidence: 99%

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Current Status of Platinum-Based Antitumor Drugs

Wong¹,

1999

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Industrial Research Fellow, investigating the coordination of technetium and rhenium to peptides and the synthesis of low molecular weight radiopharmaceuticals. His research interests centered on the applications of technetium and rhenium radiopharmaceuticals to oncology and neurology. In 1998, he joined the platinum development team at AnorMed, Inc., as a Senior Developmental Scientist. His current research interests include the design and synthesis of new Pt antitumor agents and the design of efficient processes for large-scale manufacture of Pt compounds. Christen Giandomenico received his Ph.D. degree in Chemistry from Columbia University and has held Post-doctoral positions at the University of Chicago and the Stanford Research Institute. In 1985 he joined Johnson-Matthey where he was a co-inventor of JM216, the first orally active platinum anticancer drug. He is a named inventor on six patents and is the author of 19 scientific articles. In 1996 he helped found AnorMED, a company dedicated to the discovery and development of metal-based therapeutics. He is currently Director of Chemical Development at AnorMED.

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Section: 7 Water-soluble Complexesmentioning

confidence: 99%

“…At physiological pH, the diamine chelate closes, forming a conventional platinum compound that has in vivo activity. 233…”

Section: Water-soluble Complexesmentioning

confidence: 99%

Current Status of Platinum-Based Antitumor Drugs

Wong¹,

1999

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“…The antitumor activity of cis ‐diaminedichloro‐platinum(II) (cisplatin) was serendipitously discovered by Rosenburg et al 1 in the 1960s. The side effects and narrow range of tumors in which cisplatin and relating second‐generation anticancer platinum drugs, carboplatin, nedaplatin, and oxaliplatin are efficient have led to an increase in the search for new and more effective anticancer drugs 2–12. Part of this search for new drugs includes the need to understand the kinetics of the interaction of these compounds with certain nucleophiles, especially sulfur‐donor nucleophiles.…”

Section: Introductionmentioning

confidence: 99%

Kinetic and mechanistic investigation into the influence of chelate substituents on the substitution reactions of platinum(II) terpyridine complexes

Jaganyi

Boer

Gertenbach

et al. 2008

Int J of Chemical Kinetics

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The substitution kinetics of the complexes [Pt{4 -(o -CH 3 -Ph)-terpy} Cl]SbF 6 (CH 3 PhPtCl(Sb)), (ClPhPtCl), and [Pt{4 -(o -CF 3 -Ph)-terpy}Cl]SbF 6 (CF 3 PhPtCl), where terpy is 2,2 :6 ,2 -terpyridine, with the nucleophiles thiourea (TU), N,N -dimethylthiourea (DMTU), and N,N,N ,Ntetramethylthiourea (TMTU) were investigated in methanol as a solvent. The substitution reactions of the chloride displacement from the metal complexes by the nucleophiles were investigated as a function of nucleophile concentration and temperature under pseudo-first-order conditions using the stopped-flow technique. The reactions followed the simple rate law k obs = k 2 [Nu]. The results indicate that the introduction of substituents in the ortho position of the phenyl group on the ancillary ring of the terpy unit does influence the extent of π -backbonding in the terpy ring. This controls the electrophilicity of the platinum center, which in turn controls the lability of the chloro-leaving group. The strength of the electron-donating or -withdrawing ability of the substituents correlates with the reactivity of the complexes. Electron-donating

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Unusual reactivity of cisplatin analogs that bear o-phenylenediamine ligands: Insights for the design of more effective cytotoxic agents

Köckerbauer¹,

Bednarski²

1996

Journal of Inorganic Biochemistry

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A Novel Approach to Preparing Water Soluble Prodrug Forms of Cisplatin Analogues Bearing Chelating Diamines

Cited by 5 publications

References 12 publications

Current Status of Platinum-Based Antitumor Drugs

Current Status of Platinum-Based Antitumor Drugs

Kinetic and mechanistic investigation into the influence of chelate substituents on the substitution reactions of platinum(II) terpyridine complexes

Unusual reactivity of cisplatin analogs that bear o-phenylenediamine ligands: Insights for the design of more effective cytotoxic agents

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