Chemistry Reference
In-Depth Information
Fig. 1.5
GnRH antagonist AG-045572 [
89
]
sila-pyridinium ion as a metabolite. As a result the sila-haloperiodol may provide
an alternative treatment modality for a number of neurological disorders without the
negative side effects observed with haloperidol.
Drug molecules that act as antagonists and agonists for gonadotropin-releasing
hormones (GnRH) are being explored as a means of treating various reproductive
disorders and tumors that may be linked to hormones [
93
]. One class of compounds
that is being examined for these applications are molecules that are not based on
peptides but still have the potential to behave as GnRH agonists or antagonists;
5-[(1,1,3,3,6-pentamethyl-1,3-disila-2,3-dihydro-1
H
-inden-5-yl)methyl]-
N
-(2,4,6-
trimethoxyphenyl)furan-2-carboxamide
6
falls into this category [
89
]. A sila-ana-
logue of the non-peptidic GnRH antagonist AG-045572 (Fig.
1.5
)
2
demonstrated
a retention of efficacy in spite of the insertion of silicon atoms into one of the ring
systems of the AG-045572 structure [
89
]. The insertion of silicon atoms into key
positions in existing drug compounds may present pharmaceutical researchers with
access to new libraries of bioactive compounds as well as avenues around the limi-
tations placed on drug discovery by the existing patent literature.
Few silicon-containing drug candidates have progressed to clinical trials [
3
,
80
,
94
]. One example of a silicon-based drug that is an exception to this statement is
7-[(2-trimethylsilyl)ethyl]-20(
S
)-camptothecin (BNP1350 or karenitecin) (Fig.
1.6
)
[
85
,
86
]. An analogue of camptothecin, which is isolated from the
Camptotheca
acuminata
tree, karenitecin has demonstrated a broad spectrum of activity against
experimental human tumors and is a candidate for the oral treatment of cancer. Kar-
enitecin's potency, broad spectrum of activity, oral bioavailability, lactone stability,
lack of metabolic conversion, and chemical stability make it an attractive candi-
date as a chemotherapy agent [
86
]. As of 2004 karenitecin was progressing through
Phase I and Phase II clinical trials [
85
].
Germanium-containing bioactive compounds have also been reported based on
C/Si/Ge bioisoterism [
96
].
1.3.2.2.2
Biomedical Devices Based on Silicon
One of the areas that silicon species have received a great deal of attention has been
in the area of biomedical applications. The following sections will provide a very
