Synthesis and Reactions of a New Class of Orally Active Pt(IV) Antitumor Complexes
The advent of cisplatin was a breakthrough in the chemotherapy of certain cancers. Its success, in spite of adverse effects such as nephrotoxicity, nausea and vomiting, ototoxicity and myelosuppression, attests to its efficacy1. Still, the cost of treatment, in terms of patient quality of life, underscores the need for an efficacious drug with milder side effects. Carboplatin is an example of an agent specifically developed to reduce side effects while retaining the antitumor activity of cisplatin2. Its tremendous success, following its introduction in Europe and the US, attests to the importance of addressing patient quality of life. Although, oral chemotherapeutic agents are not presently a significant factor in cancer treatment, a properly designed agent could offer significant advantages in terms of a patients’ comfort and convenience, and anticipates the possibility of outpatient chemotherapy. At Johnson Matthey, in conjunction with the Institute of Cancer Research and Bristol-Myers Squibb, a portion of our platinum antitumor drug discovery program is devoted to the design and development of an orally active platinum antitumor drug. This paper describes the synthesis, reactions, and a few of the biological properties of a new class of antitumor agents that possess many characteristics required of an orally active antitumor agent.
KeywordsAntitumor Activity Antitumor Agent Mouse Tumor Model Mild Side Effect Lipophilic Side Chain
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- 1.Wiltshaw, E, presented at symposium Carboplatin: Current Status and Future Prospects. Stockholm, June 19, 1985.Google Scholar
- 5.Morgan, S.E.,; Boxall F.E.; Murrer, B.A.; Giandomenico C. M.; Wyer S.B.; Harrap, K.R. Sixth Intl. Symp. on Platinum and other Metal Coord. Compds., 1991, 229.Google Scholar
- 6.Prof. Jon Zubieta, Syracuse University, private communication.Google Scholar
- 8.Stephen G. Chancey, Steven Wyrick, Gail Kaun Till, Cancer Research, 1990, 50, 4539–4.Google Scholar
- 9.(a)Blatter, E.E., Vollano, J.F.; Krishna, B.S.; Dabrowiak, J.C. Biochemistry, 1984, 23, 4817.Google Scholar
- (b).Evans, J.E.; Green, M.; Inorg. Chim. Acta, 1987, 183-4.Google Scholar
- 11.Kelland, L.R.; Abel, G.; Harrap, K.R. Proc. A.A.C.R., 1989, 609.Google Scholar
- 12.Binks, S.P; Dobrota, M. Biochemical Soc. Trans., 1986, 14, 694–5.Google Scholar
- 13.Morgan, S.E.; Webster, L.K.; Boxall, F.E.; Siddik, Z.H.; Murrer, B.A.; Harrap K.R. presented in Sixth NCI-EORTC Symposium on New Drugs in Cancer Therapy, 1989.Google Scholar
- 14.Goddard, P.M., Valenti, M.R., Murrer, B.A., Harrap K.R., presented in Sixth NCI-EORTC Symposium on New Drugs in Cancer Therapy, 1989.Google Scholar
- 15.Harrap, K.R. Cancer Treat. Rev., 1985, 21-33.Google Scholar