A pharmacophore for high affinity PAF antagonists. II. Hydrophobicity study using the molecular lipophilicity potential.

Platelet-activating factor (PAF) is a powerful phospholipid-derived autacoid involved in many physiopathological mechanisms. Many PAF antagonists have been synthesized and evaluated as therapeutic candidates. In a previous report, we have described an electronic pharmacophore of PAF antagonists using the molecular electrostatic potential.

A pharmacophore for high affinity PAF antagonists. I. Electronic model using molecular electrostatic potential.

PAF is a powerful phospholipid-derived autacoid involved in many physio-pathological mechanisms. Many PAF antagonists have been synthesized and assayed for therapeutic purposes. In this study, molecular electrostatic potential is used to compare the electronic properties of 48 'heterocyclic sp2 nitrogen' highly potent PAF antagonists, belonging to six series (nine hetrazepines, five pyrrolo[1,2-c]thiazoles, 14 carboxamides, nine dihydropyridines, nine pyridinylthiazolidines and two imidazo[4,5-c]pyridines).

Determination of a PAF antagonist pharmacophore using combined Molecular Electrostatic Potential and Molecular Lipophilicity Potential.

PAF is a potent lipid mediator involved in many pathological disorders, such as platelet aggregation, immuno-inflammatory reactions, vascular disorders, septic shock and bronchoconstriction. We chose to study the electronic and lipophilic properties of eleven PAF antagonists, comprising five tetrahydrofuran derivatives, four hetrazepines, the ginkgolide BN-52021 and the pyrrolo-thiazole derivative RP-59227. A Molecular Electrostatic Potential (MEP) contour drawn at -25 kCal/Mol shows three electronegative areas in most compounds.

The determination of bromazepam in plasma by reversed-phase high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatographic method has been developed for the determination of bromazepam, an anxiolytic benzodiazepine, in plasma. After a single-step extraction from alkalinized plasma with diethyl-ether in the presence of an internal standard (alpha-hydroxy-triazolam), the residues were chromatographed on a reversed-phase Nova Pak 5 microns C18 column, with a mobile phase of acetonitrile-water-triethylamine (700:300:4, v/v/v) adjusted to pH 7.4 with orthophosphoric acid.