Chemistry Reference
In-Depth Information
H
3
N
Cl
H
3
N
Cl
Pt
Pt
H
3
N
Cl
Cl
NH
3
cisplatin
transplatin
H
2
C
H
C
O
O
H
N
H
3
N
O
C
O
C
C
H
2
C
H
2
H
Pt
Pt
C
CH
2
H
3
N
H
2
O
C
H
2
O
C
H
2
O
O
carboplatin
oxaliplatin
O
H
3
C
C
O
H
3
N
Cl
H
3
N
Cl
C
Pt
Pt
C
HC
N
Cl
H
2
Cl
CH
2
CH
2
O
CH
2
CH
2
HC
C
CH
2
H
CH
3
C
H
3
C
O
satraplatin
picoplatin
Figure 5.1
Structures of cisplatin and transplatin, and of other platinum drugs already
approved or in the pipeline
(active in patients with colorectal cancer), satraplatin (the fi rst orally administered
platinum drug, which shows promise in patients with prostate cancer) and picoplatin
(currently in phase III trials against small-cell lung cancer, prostate cancer and
colorectal cancer). These drugs are also shown in Figure 5.1 .
Improved delivery of platinum drugs to tumours is also being studied using
liposomal - based
17,18
or copolymer - based products,
19 - 21
localized administration
22
and
also coadministration with specifi c modulators to prevent platinum-resistance
mechanisms.
23 - 26
Reference 27 gives a very recent overview of the fi eld.
Cisplatin is a simple neutral inorganic compound having square planar geom-
etry and containing a platinum(II) centre bonded to two nonlabile ammine ligands
(carrier ligands) and two labile chlorido ligands (leaving groups) in a
cis
confi gura-
tion. Transplatin has the same composition but the ligands are in a
trans
arrange-
ment. Whereas cisplatin is active against a wide variety of tumours, transplatin is
inactive and toxic.
28
The structures of cisplatin and transplatin are also shown in
Figure 5.1 .
Since cisplatin and its analogues were found to be tumour active, while trans-
platin and its analogues were found to be inactive, it was suggested that, in order to
