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Chapter 4<br />
Synthesis of highly substituted pyrazolopyrimidine<br />
Silvia Selleri et al. 19 have been developed a new class of N,N-diethyl-(2-<br />
arylpyrazolo[1,5-a]pyrimidin-3-yl)acetamides, (Figure-4) as azaisosters of Alpidem,<br />
and their affinities for both the peripheral (PBR) and the central (CBR)<br />
benzodiazepine receptors were evaluated. Binding assays were carried out using both<br />
[ 3 H]PK 11195 and [ 3 H]Ro 5-4864 as radio ligands for PBR, whereas [ 3 H]Ro 15-1788<br />
was used for CBR, in rat kidney and rat cortex, respectively. The tested compounds<br />
exhibited a broad range of binding affinities from as low as 0.76 nM to inactivity and<br />
most of them proved to be high selective ligands for PBR. The preliminary SAR<br />
studies suggested some of the structural features required for high affinity and<br />
selectivity; particularly the substituent on the pyrimidine moiety seemed to play an<br />
important role in PBR versus CBR selectivity. A subset of the highest affinity<br />
compounds was also tested for their ability to stimulate steroid biosynthesis in C6<br />
glioma rat cells and some of these were found to increase pregnenolone formation<br />
with potency similar to RO 5-4864 and PK 11195.<br />
Figure-4<br />
John E. Tellew et al. 20 has discovered an antagonist of the corticotropinreleasing<br />
factor (CRF) neuropeptide may prove effective in treating stress and anxiety<br />
related disorders. In an effort to identify antagonists with improved physico-chemical<br />
properties a new series of CRF1 antagonists were designed to substitute the propyl<br />
groups at the C7 position of the pyrazolo[1,5-a]pyrimidine core with heterocycles.<br />
Compound (Figure-5) was identified as a high affinity ligand with a pKi value of 8.2<br />
and a functional CRF1 antagonist with IC 50 value of 7.0 in the in vitro CRF ACTH<br />
production assay.<br />
N<br />
O<br />
N<br />
H<br />
N<br />
N<br />
N<br />
N<br />
R<br />
O<br />
Figure-5<br />
Department of Chemistry, <strong>Saurashtra</strong> university, Rajkot-360005 123