P2Y12 receptor becomes a favorable target for therapeutic antiplatelet agents. Reversible P2Y12 receptor antagonists have more benefits than the irreversible ones on rapid absorption, onset of action and higher inhibition of platelet aggregation. As potent reversible P2Y12 receptor antagonists, piperazinyl-glutamate-pyridines exhibit a significant improvement in efficacy while maintaining a better safety profile than the irreversible ones. In this study, we developed a 3D pharmacophore model with r2 = 0.966 based on a set of piperazinyl-glutamate-pyridines showing the important pharmacophore features (one hydrogen bond acceptor, one hydrogen bond donor, one ring aromatic and one hydrophobic feature) which is necessary for reversible P2Y12 receptor antagonists. The obtained pharmacophore models were validated by using well-known methodologies such as test molecules and Fischer’s randomization method. A docking study was also performed based on the recently released P2Y12 receptor crystal structure (PDB ID: 4NTJ) which revealed key residues (Tyr105, His 187 and Lys280) in the receptor–ligand interaction. The docking results were well in agreement with the pharmacophore model that raised the model’s reliability. The pharmacophore model was further confirmed by estimating the activity of six known drugs which can distinguish the reversible P2Y12 receptor antagonists from the irreversible ones. The results of our study provide confidence for the utility of the selected chemical features to retrieve further compounds as reversible P2Y12 receptor antagonists.

As increasing drug-resistance poses an emerging threat to public health, the development of novel antibacterial agents is critical. We developed a workflow consisting of various methods for de novo design. In the workflow, 2D-QSAR model based on molecular fingerprints was constructed to extract the bioactive molecular fingerprints from a data set of DNA–gyrase inhibitors with new structure and mechanism. These fingerprints were converted into molecular fragments which were recombined to generate compound library. The new compound library was virtually screened by LigandFit and Gold docking, and the results were further investigated by pharmacophore validation and binding mode analysis. The workflow successfully achieved a potential DNA–gyrase inhibitor. It could be applied to design more novel potential DNA–gyrase inhibitors and provide theoretical basis for further optimization of the hit compounds.