Organometallic titanium, vanadium, niobium, molybdenum and rhenium complexes — early transition metal antitumour drugs

Abstract

Titanocene dichloride, bis(cyclopentadienyl)dichlorotitanium(IV), [(C5H5)2TiCl2] (Figure 6.1) is the main representative of the early transition metal antitumour agents to show antitumour activity against numerous experimental animal and human carcinomas (Köpf and Köpf-Maier, 1979; Köpf-Maier Hesse and Köpf, 1980; Köpf-Maier, Leitner and Köpf, 1980; Köpf-Maier and Köpf, 1988) and entered phase I clinical studies in December 1991. It is one of the first non-platinum antitumour agents to be detected after the discovery of the tumour-inhibiting properties of cis-diamminedichloroplatinum(II) (cisplatin, Figure 6.1) in 1969 (Rosenberg et al., 1969; Rosenberg, 1973). As a chemical compound, titanocene dichloride was described by Wilkinson and Birmingham in 1954 and is today an important organometallic compound used as ‘Ziegler-Natta-catalyst’, e.g. for the polymerization of alkenes and organosilicon compounds, and as a precursor of reagents in organic synthesis (Haiduc and Zuckerman, 1985).