Synthesis, biological evaluation and molecular docking studies of 2-piperazin-1-yl-quinazolines as platelet aggregation inhibitors and ligands of integrin αIIbβ3

Interpretation of Quantitative Structure–Activity Relationship Models: Past, Present, and Future

“…In real models it is not single descriptors but whole groups that represent particular physicochemical factors and the fragment of interest should be removed in terms of all descriptors belonging to a certain group representing a single physicochemical factor. Simplex representation of molecular structure perfectly suits this interpretation strategy because each atom is labeled by different physicochemical parameters which are taken into account for generation of simplex descriptors. ,, The described SPCI approach based on simplex descriptors was implemented in the open-source software tool with a graphical user interface . However, this approach is not limited using only simplex descriptors; other suitable descriptors can be used as well.…”

Emergence of Small-Molecule Non-RGD-Mimetic Inhibitors for RGD Integrins

“…The authors later confirmed this hypothesis using a series of analogues in which this distance was varied. 62 This study showed that shortening the compound by one carbon (compound 15) caused a greater than 100-fold decrease in potency, and lengthening by one carbon (compound 16) was also unfavorable, resulting in micromolar inhibition, Figure 9.…”

“…The virtual hit compounds were synthesized and through biological screening, one low nanomolar inhibitor for the closed receptor was successfully identified (compound 14). 61 Docking studies carried out using compound 14 showed a similar binding mode to that of 9, but this analogue showed superior levels of potency with an IC 50 of 11 nM, Figure 9. A key feature of their model for a closed form binder was a distance of 15.8 • between two positively charged centers.…”

“…α IIb β 3 non-RGD-mimetic inhibitors designed from 9 . IC 50 for inhibition of ADP-induced aggregation of platelets (human). , …”

“…A more recent report from Polishchuk et al used quantitative structureÐactivity relationship (QSAR) and pharmacophore models to screen a number of databases for novel α IIb β 3 antagonists, but no hit compounds were identified. 61 The authors concluded that this was the result of the low number of zwitterionic compounds available in the commercial libraries used for their screen. receptor.…”