Chemistry Reference
In-Depth Information
Fig. 1.4
Examples of silicon-containing drug compounds
of Pc 4
2
block copolymer micelles have been explored as means of delivering the
drug
in vivo
[
77
].
Compounds
3
and
4
represent a class of molecules designed to behave as bioiso-
steres of stabilized protease acyl-enzyme intermediates thereby inhibiting the activ-
ity of those enzymes; the molecule enters the enzyme active site and effectively
binds in that position limiting access to the active site by the natural substrate for the
enzyme [
75
,
78
,
79
]. Compound
3
, which targets angiotensin converting enzyme
(ACE), has demonstrated an IC
50
= 14 nM while
4
has an IC
50
= 2.7 nM when chal-
lenged with HIV protease [
78
].
Haloperidol is a dopamine receptor antagonist used in the treatment of neurolog-
ical disorders such as schizophrenia and Parkinson's disease. However, in addition
to its clinical uses haloperidol also exhibits neurotoxic side effects [
88
]. It has been
postulated that a pyridinium metabolilte of haloperidol is responsible for the ob-
served neurotoxic behavior of the drug because of its close structural resemblance
to 1-methyl-4-phenylpyridinium which has been shown to induce Parkinson-like
symptoms [
91
,
92
]. The sila-haloperidol
5
analogue of haloperidol does not form a
