Pharmacophore multiplets are useful tools for 3D database searching, with the queries used ordinarily being derived from ensembles of random conformations of active ligands. It seems reasonable to expect that their usefulness can be augmented by instead using queries derived from single ligand conformations obtained from aligned ligands. Comparisons of pharmacophore multiplet searching using ra...

The central role of phosphodiesterase-5 (PDE5) is to hydrolyze the cyclic guanidine monophosphate which leads male erectile dysfunction. To inhibit the PDE5 activity, integrated computer-aided drug design technologies were utilized to generate pharmacophore modeling, database screening and docking methodologies. 3D pharmacophore models are generated using HypoGen to identify the critical chemic...

In the present study we have investigated whether pharmacophore models may account for the activity and selectivity of the known cyclooxygenase-2 (COX-2) selective inhibitors of the phenylsulfonyl tricyclic series, i.e., Celecoxib (1) and Rofecoxib (3), and whether transferring this structural information onto the frame of a nonsteroidal antiinflammatory drug (NSAID), known to tightly bind the ...

The protozoan parasites of the genus Trypanosoma sp. and Leishmania sp. are responsible for neglected diseases like Chagas’ disease, African sleeping sickness or Leishmaniasis. The trypanothione synthetase (TryS) is an attractive new drug target for the development of trypanocidal and antileishmanial drugs [1]. In our virtual screening campaign for targeting the trypanothione synthetase (TryS) ...

Adenosine kinase (AK) is a ubiquitous intracellular enzyme, which catalyzes the phosphorylation of adenosine (ADO) to adenosine monophosphate (AMP). AK inhibitors have therapeutic potential as analgesic and antiinflammatory agents. A chemical feature based pharmacophore model has been generated from known AK inhibitors (26 training set compounds) by HypoGen module implemented in CATALYST softwa...

We present a ligand-based virtual screening technique (PhAST) for rapid hit and lead structure searching in large compound databases. Molecules are represented as strings encoding the distribution of pharmacophoric features on the molecular graph. In contrast to other text-based methods using SMILES strings, we introduce a new form of text representation that describes the pharmacophore of mole...

Pyrazolines 7-10 were designed as novel CB(1) receptor antagonists, which exhibited improved turbidimetric aqueous solubilities. On the basis of their extended CB(1) antagonist pharmacophore, hybrid molecules exhibiting cannabinoid CB(1) receptor antagonistic as well as acetylcholinesterase (AChE) inhibiting activities were designed. The target compounds 12, 13, 20, and 21 are based on 1 (tacri...

Three neurokinin (NK) antagonist pharmacophore models (Models 1-3) accounting for hydrogen bonding groups in the 'head' and 'tail' of NK receptor ligands have been developed by use of a new procedure for treatment of hydrogen bonds during superimposition. Instead of modelling the hydrogen bond acceptor vector in the strict direction of the lone pair, an angle is allowed between the hydrogen bon...