- Vinorelbine (Navelbine®, 1989), a semisynthetic analogue of VLB,
used in the treatment of non-small cell lung cancer.
- Vinflunine, (Javlor®, 2010), another semisynthetic derivative,
used to treat advanced transitional cell bladder and urothelial
tract cancer.
The long-standing industrial production of VLB and VCR made
these two bisindoles a convenient starting point for synthetic
chemists who attempted to design even more potent but less toxic
semisynthetic analogues. When looking at the molecular structures
(Fig. 1) and the biological activities of the aforementioned
bisindoles that went to market, it is apparent that relatively small
structural changes lead to significantly different oncological and
toxicological profiles. For this reason the bisindole family has been,
and continues to be, an important but difficult field of chemical
research that has given rise to many inventive and elegant synthetic
solutions, and keeps providing new challenges [3–8].