Docetaxel fluorine-containing analog

Ojima, I., Kuduk, S. D., Chakravarty, S., el al. (1997) Anovel approach to the study of solution structures and dynamic behavior of paclitaxel and docetaxel using fluorine-containing analogs as probes. J. Am. Chem. Soc., 119, 5519-5527. 

Figure 10. Fluorine-containing analogs of paclitaxel and docetaxel (18).

As Table I shows, several of the new fluorine-containing taxoids exhibit similar or slightly weaker activity as compared to paclitaxel and docetaxel. 3 -(4-Fluorophenyl)paclitaxel (SB-T-3101) shows slightly decreased activity compared to the parent compound, while 3 -(4-fluorophenyl)docetaxel (SB-T-3001) and 10-acetyl-3 -(4-fluorophenyl)docetaxel (SB-T-3002) show comparable activity to docetaxel. 3 -(iV-Fluorobenzoyl)paclitaxel (SB-T-13103) is similar to SB-T-3101 in activity, while 3 -A/-fluorobenzoyl-3 -(4-fluorophenyl)paclitaxel (SB-T-31031) is about 10-fold weaker as compared to paclitaxel, showing that the incorporation of two fluorines at these positions is unfavorable to the activity. Thus, it appears that fluorine incorporation at the para-position on the side chain aromatic rings of paclitaxel decreases the activity, while exhibiting little effect on docetaxel analogs. 

Synthesis and biological activity of 3 -trifluoromethyl-docetaxel analogs (15,26). During the course of the structure-activity relationship study of fluorine-containing taxoids, we designed a series of taxoids bearing a trifluoromethyl moiety at the C-3 position in place of the phenyl group. For the synthesis of a series of 3 -CF3-taxoids... 

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