Irinotecan, anticancer agent

Ion transfer, 14 (1977) 1 Irinotecan, anticancer agent, 34 (1997) 68 Isothermal titration calorimetry, in drug design, 38 (2001) 309... 

In recent years, however, some of the greatest emphasis has been placed on the search for anticancer and antiviral agents derived from natural products. Success in that area has not heen as great as that achieved in other helds. Since 1960, only seven plant-derived drugs have heen approved by the FDA for use as anticancer agents. Four of those drugs, vinblastine, vincristine, etoposide, and teniposide, were discovered in the 1950s. The last three—Taxol , topotecan, and irinotecan—were discovered and approved much more recently. 

Many anticancer agents have their origins in pharmacognosy, including paclitaxel, etoposide, and the camptothecin analogues, topotecan and irinotecan, to name just a few. The dolastatins are a unique class of compounds isolated from the Indian Ocean sea-hare Dolabdla auricularia that are referred to as depsipeptides,... 

Innocent E, Iyer L, Ratain MJ. Pharmacogenetics of anticancer agents Lessons form amonafide and irinotecan. Drug Met. Disp. 2001 29 596-600. 

Pharmacia Upjohn developed a practical synthesis toward the anticancer agent Irinotecan (Camptosar, 24), which involved an enzymatic resolution step to provide the strategic intermediate 23 (Scheme 7) [65,66]. Lactone 23 could be produced by internal esterification of oxidized (S)-diol 21, which in turn was obtained by biocatalytic resolution of mc-21. An asymmetric acetylation was achieved with isopropenyl acetate catalyzed by Amano PS-30 Pseudomonas cepacia) lipase immobilized on Celite and could be driven to 60% conversion. (S)-21 was isolated in 38% yield and with 99% optical purity, whereas the unwanted (i )-stereoisomer 22 was recycled in a three-step procedure. Changing the support to Celite 521 significantly increased the reaction rate, as did rais-... 

The study of natural products, or Nature s Combinatorial Library , has had a long history as a source of drugs, and plants have historically been at the forefront of natural product drug discovery. In the anticancer area, for example, vinblastine and vincristine, etoposide, paclitaxel (Taxol), docetaxel, topotecan, and irinotecan, among others, are all plant-derived natural products or modified versions of plant compounds, while antimalarial therapy would be much poorer without quinine and artemisinin and the drugs derived from these plant products. This chapter provides an overview of the major medicinal agents that are themselves natural products isolated from plants or are chemical modifications of such lead compounds. It covers the therapeutic areas of cancer, HIV, malaria, cardiovascular, and central nervous system (CNS) diseases. Natural plant products have also made contributions in areas such as immunomodulatory and antibiotic activities," and the reader is referred to the cited reviews for information on these areas. 

Some of the clinically important drugs that have been identified to be mechanism-based CYP3A4 inhibitors include antibiotics (e g., erythromycin), anticancer drugs (e.g., irinotecan), antidepressants (e g., fluoxetine and paroxetine), anti-FIIV agents (e.g., ritonavir and... 

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