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