Secondary phosphine oxides R2P(O)H are a relatively stable tautomeric form of secondary phosphinous acids R2P–OH that with imine/iminium species, or their donors, compounds P(O)–Csp3–N linkage (the phospha-Mannich reaction). These can be referred to as (α-aminoalkyl)phosphine oxides, (α-phosphinoylalkyl)amines, P(O),N-acetals. Compared P–Csp3–N linkages P,N-acetals, products reactions involving...

The present study describes the implementation of comparative molecular field analysis (CoMFA) to develop two 3D-QSAR (quantitative structure-activity relationship) models (CoMFA models 1 and 2) of the cannabimimetic (aminoalkyl)indoles (AAIs) for CB1 cannabinoid receptor binding affinity, based on pKi values measured using radioligand binding assays that displace two different agonist ligands,...

DNA ligases are important enzymes which catalyze the joining of nicks between adjacent bases of double-stranded DNA. NAD+-dependent DNA ligases (LigA) are essential in bacteria and are absent in humans. They have therefore been identified as novel, validated and attractive drug targets. Using virtual screening against an in-house database of compounds and our recently determined crystal structu...

The therapeutic application of siRNA suffers from poor bioavailability caused by rapid degradation and elimination. The covalent attachment of PEG is a universal concept to increase molecular size and enhance the pharmacokinetic properties of biomacromolecules. We devised a facile approach for attachment of PEG molecules with a defined molecular weight, and successful purification of the result...

We have investigated the mechanism of TOP-53 distribution to the lung and lung-localized tumor. In contrast to etoposide (VP-16), TOP-53 contains a basic aminoalkyl group that may predispose it to interact specifically with phospholipids, consequently leading to an increase of drug accumulation in the tissues. Therefore, we have studied its interaction with phospholipids in vitro using an organ...

The aim of this study was to prepare, using taste-masked granules, tablets which can rapidly disintegrate in saliva (rapidly disintegrating tablet), of drugs with bitter taste (pirenzepine HCl or oxybutynin HCl). The taste-masked granules were prepared using aminoalkyl methacrylate copolymers (Eudragit E-100) by the extrusion method. None of the drugs dissolved from the granules (% of dissolved...

1. The preparation of a series of compounds derived from diamines by replacing one amino group by a dimethylsulphonium, isothiuronium, trimethylammonium, NN'-dimethylimidazolium or N-methylpyridinium species is described. 2. The behaviour of these compounds as substrates of pig kidney diamine oxidase is reported. All but the trimethylammonium compounds proved to be substrates. 3. Many of these ...