3458
Med Chem Res (2012) 21:3455–3459
Fig. 1 Correlation between pKa
values and pKi SERT of
compounds 1–7 (left) and 13–22
(right)
Results and discussion
confirm that the applied potentiometric method is useful in
characterization of the acid–base properties of closely
related compounds contrary to values of pKa predicted by
Pallas program. There is no correlation between values of
pKa predicted by Pallas program and experimental. The
moderate correlation between activity for SERT and pKa,
indicating that acid–base properties are one of the impor-
tant factors, which could influent and modify the activity
for SERT.
The library consisting of twenty two compounds was
investigated. Based on their structural features, this library
could be divided into two sublibraries: the first contained
various arylpiperazinylpropyl derivatives of imidazo[2,1-
f]theophylline, and the second derived from imidazolidine-
2,4-dione. Comparing the affinity for SERT obtained for
imidazo[2,1-f]purine-2,4-dione and respective imidazoli-
dine-2,4-dione analogues revealed higher activity in the
first mentioned series. The most potent SERT ligands
were compounds 3, 6, and 7 with pKi within the range of
7.25–7.53, which were containing 2,3-dichloro or 3-chlor-
ophenylpiperazine fragment in their structures. Compounds
1, 2, 9, 11, 12, 15, 16, 19, and 20 displayed moderate to very
low affinity for the SERT (5.61–6.95), whereas other were
practically devoid of any affinity.
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imidazo[2,1-f]purine-2,4-dione) are potent dual ligands for
SERT and 5-HT1A receptor (pKi [ 7.5) and were classified
to the further pharmacological studies. The obtained results
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