Chemistry Reference
In-Depth Information
N
R
O
N
HO
O
N
N
O
N
O
O
OH
O
OH
C1
Camptothecin (CPT) R
H
C2
10-Hydroxycamptothecin R
=
=
OH
C3
Topotecan (Hycamptin)
NH
3
+
Cl
−
H
N
C
=
N-NHCO
CH CH
2
R
N
O
O
O
N
N
O
N
N
O
O
C4
Irinotecan (Camptosar)
O
OH
C5
7-(Acylhydrozono)-formyl-
camptothecins, R = H or OH
O
OH
N
NH
O
O
O
HN
O
N
O
O
N
N
O
O
O
O
H
3
CO
OCH
3
O
OH
N
O
C6
OH
N
H
3
CO
OCH
3
OH
O
C7
Si
O
OH
NO
2
NH
2
HO
O
N
O
O
N
N
N
N
N
O
O
O
C9
(9-NC)
C9
′
(9-AC)
O
C8
DB-67
OH
O
O
OH
C9
Rubitecin:
C9
[9-nitro-camptothecin (9-NC)] is metabolized to
C9
OH
′
[9-amino-camptothecin (9-AC)]
Figure 14.3
Structures of natural and synthetic camptothecins.
Poor water solubility of the natural products led to the development of the
semisynthetic, more water-soluble analogs topotecan (Hycamptin,
C3
)and
irinotecan (Camptosar,
C4
), which are used primarily for the treatment of
advanced ovarian and metastatic colorectal cancers, respectively (39). Some
CPT analogs, such as
C5
, synthesized in the laboratories of the authors
showed greater topo I inhibition than CPT (40). Additional CPT analogs also
are of interest in combination regimens as radiation sensitizers (41). Two
epipodophyllotoxin-campothecin conjugates,
C6
and
C7
, from the laboratories
