Simple Ester Derivatives and Prodrugs

A number of different simple ester prodrugs have been prepared. In addition to the 2 -esters described in the previous review (166, 350-352), various other simple ester derivatives have been prepared such as the ester 10.1.1 (353) and various amino derivatives such as 10.1.2-10.1.3 (354) in this latter case the 3 -phenyl group was also replaced by a number of different aryl groups, although the best activity was reported for the analog 10.1.3 with Ar = Ph. 

Water-soluble derivatives such as 10.1.4 and a number of simpler ester derivatives have been prepared by enzymatic acylation of taxol (555), and substituted benzoate esters 10.1.5 and 10.1.6 have been prepared (356). 

Both mono- and bis-malic acid esters of taxol have been made, and the sodium salt of the 2 -malyl derivative 10.1.7 showed enhanced activity and less toxicity as compared with taxol in the P-388 in vivo mouse leukemia model (357). Simple esters such as 10.1.8 have been prepared to enhance association with a liposomal lipid carrier in plasma (358), and the carbonate derivative 10.1.9 and related compounds were found to be as active as taxol in the M109 system (359). 

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