Chemistry Reference
In-Depth Information
be less active in most cases, whereas C-3
0
-CF
3
docetaxel analogs were more potent
in either normal or MDR tumor cell lines.
25
C-3
0
-thiocarbamate paclitaxel analogs
exhibited superior activitiy to that of the parent compound in HCT-116 drug-resis-
tant tumors.
34
Conjugated double and triple bonds in C3
0
-N analogs make positive
contributions to the activity against MDR tumor cells, as depicted in Section
3.2.1.3.
32
O
AcO
Bz
O
O
NH
O
Boc
OH
O
NH
O
OH
Ph
O
R
1
O
OH
OH
HO
H
O
O
HO
H
O
O
O
AcO
O
O
O
R
2
F
F
109a
R
1
=CH
2
CH(CH
3
)
2
, R
2
=OMe
109b
R
1
=CH=C(CH
3
)
2
, R
2
=OMe
109c
R
1
=CH=C(CH
3
)
2
, R
2
=N
3
110
Battaglia et al. prepared a series of 2
0
-(S)-Me of paclitaxel analogs, and most
compounds are more active toward drug-resistant A2780 human lung carcinoma
and drug-resistant MCF-7 human breast carcinoma.
20
For the best compound 6c
among them, it exerted better antitumor effects on drug-resistant tumors than pacli-
taxel, docetaxel, and IDN5109 (113).
A Korean group, Roh et al., found that some C3
0
-N-debenzoyl N-acyl analogs,
without any change of substitutions at other sites, can exhibit high potencies toward
MDR tumors. Even if less active against sensitive tumor cells, all N-acyl analogs
bearing conjugated bonds tested in bioassays were as much as seven times more
active than paclitaxel against MDR tumor cells.
32
In a library with C-10-modified paclitaxel analogs with various acyl groups,
some of them, including short-chain aliphatic, most alicyclic, and some nitrogen-
containing aromatic and heteroaromatic analogs, were more effective toward drug-
resistant MCF-7R breast cancer cell lines.
40
Two C-10 spiro epoxides were pre-
pared and biologically evaluated.
67
Taxoids 42b is more active against the MDR
tumor cell line HCT-VM46 than is paclitaxel, and 42a is almost one order of mag-
nitude less active.
In 2002, it was found that a 2-diflurobenzoyl paclitaxel analog (60d) exhibited
comparable activity with paclitaxel, are best in C-2 mono- and di-substituted ben-
zoyl analogs and better than 9a and 9b in paclitaxel-resistant HCT-116/VM46 can-
cer cell lines.
77,78
It was also reported that some 2-debenzoyloxy-2a-benzamido
docetaxel analogs were comparably cytotoxic with paclitaxel toward some drug-
resistant tumor cell lines.
99
Search WWH ::
Custom Search