2 -Deoxy-2 - docetaxel

DJ-927 (49), a 9-dihydro-7-deoxy docetaxel analog under its phase 1 clinical trial, was effective against various mmors, especially P-gP overexpressing MDR tumors in vivo. Additional investigation showed that it is not a P-gP substrate and its cytotoxicity is not influenced by P-gP modulators. Although the authors proposed that the effectiveness of DJ-927 may be partly from higher intracellular accumulation, its mechanism against MDR tumors should be addressed in the fumre. ... 

In the early 1990s, the Bartons protocol was widely applied to the preparation of deoxygenated derivatives at many sites on taxanes. Enhancement of cytotoxicity was observed for many 7-deoxy paclitaxel and docetaxel analogs, along with a... 

Bourchard et al. attempted to reduce the 7,19-cyclopropane docetaxel analog 92a electrochemically. Besides the major 10-deoxy product 92b, C-ring expanded 19-nor analog 93 was obtained as a minor product. Taxoid 93 did not exhibit any activity in both cytotoxicity and tubulin binding assays, although its conformation is analogous to that of docetaxel. 

In 2001, two D-thia analogs, 5(20)-thia-docetaxel 97a and 7-deoxy-5(20)-thia-docetaxel 97b, were synthesized. Compound 97a is two orders of magnitude less cytotoxic than paclitaxel, but it retained tubulin assembly ability stronger than in a previous report. Meanwhile, 97b is inactive in tubulin assay and 3 times more cytotoxic than 97a against KB cells, but it is still much less active than both 7-deoxy-lO-acetyl-docetaxel and docetaxel. 

Reduction of taxol or docetaxel with Sml2 under modified conditions has given both 9/3-dihydro and lO-deoxy-9/3-dihydro derivatives. Thus... 

Uoto et al synthesized a number of 2 -deoxy-2 -(difluoro)docetaxel derivatives. The parent compound 8.6.6 was prepared by coupling 7,10-(di-Troc)-lO-deacetylbaccatin III with 3-(r-butoxycarbonylamino)-2,2-difluoro-3-phenylpropanoic acid in the presence of di-2-pyridylcarbo-nate and DMAP. In an in vitro study using P388 tumor cells, 8.6.6 had a GI50 value of 21.0ng/mL compared with 30.4ng/mL for taxol 329). 

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