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Paclitaxel analogs

PACLITAXEL ANALOGS ACTIVE AGAINST NORMAL TUMOR CELLS... [Pg.74]

Steric hindrance, that is, the introduction of (5)-Me to C-2, while 2 (/ )-OH is retained, makes a positive contribution to the antimmor activity as well as to the tubulin binding ability. This result may have come from the reduced rotation of the side chain, which thus enhances the ratios of bioactive conformers in all con-formers. The preparation of 2 -Me analog was usually undertaken by (3-lactam approach, in which 3-keto-(3-lactam was attacked by a nucleophile to yield stereo-selectively 3-methyl-3-OH (equivalent to the 2 position in paclitaxel) (3-lactam ready for attachment to baccatin core stmcmres. Battaglia et al. prepared a series of 2 (5)-Me of paclitaxel analogs from 10-DAB and 14(3-OH-10-DAB with different C-3 and 3 -A substitutents, and all compounds 6a-e are comparable with or more active than paclitaxel toward A2780 human lung carcinoma in vitro. °... [Pg.77]

Ali et al. reported " the synthesis of a series of C3 -f-butyl paclitaxel analogs with C3 -N amides and carbamates, among which A-debenzoyl-A-(2-thienoyl) analog 12 was the most potent. Although equipotent to docetaxel, and about 25 times more water soluble than paclitaxel, this taxane was not superior to analog 13 reported earlier. [Pg.80]

A BMS research group found that 3 -r-butylaminocarbonyloxy paclitaxel analogs 14a and 14b (regioisomers of docetaxel and its 10-Ac derivative) were several times less active than paclitaxel in vitro, but 14b was equipotent to paclitaxel in vivo. They also prepared 3 -A-thiocarbamate and C3 -A-thiourea bearing analogs. Although C3 -A-thiocarbamate was found to be more potent than paclitaxel and docetaxel in both tubulin polymerization and cytotoxicity assays, thioureas are usually less active. ... [Pg.80]

Datta et al. synthesized 10-epi and 9a-OH paclitaxel analogs by iterative oxidation-reduction transformations, furnishing 39-41. lO-Epi pachtaxel 39a and 10-deacetyl paclitaxel 39b are slightly more active than pachtaxel in both cytotoxicity and tubuhn binding assays, whereas their 9(R) counterparts 40 are comparable... [Pg.87]

C-4 OMe paclitaxel analog 88 exhibited 10 times the reduced activity, whereas a change of 3 -Ph and 3 N-Bz to 2-furyl and Boc, respectively, did improve the activity by about ten times.This result demonstrated the importance of the C-4 carbonyl group. [Pg.99]

A paclitaxel analog with a C4—C6 bridge, built on the connection of a carboxyl group of 4-glutarate and the hydroxyl group of 6a-hydroxyacetate, was found almost inactive. This observation was in accordance with the hypothesis that the Southern Hemisphere of paclitaxel binds to the tubulin receptor. [Pg.100]


See other pages where Paclitaxel analogs is mentioned: [Pg.231]    [Pg.138]    [Pg.138]    [Pg.138]    [Pg.138]    [Pg.138]    [Pg.138]    [Pg.139]    [Pg.184]    [Pg.74]    [Pg.78]    [Pg.79]    [Pg.82]    [Pg.87]    [Pg.90]    [Pg.91]    [Pg.92]    [Pg.95]   
See also in sourсe #XX -- [ Pg.92 , Pg.111 , Pg.112 , Pg.123 ]




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Paclitaxels

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