Guy Devaux

Synthesis and binding affinities of a series of 1,2-benzisoxazole-3-carboxamides to dopamine and serotonin receptors

Summary A series of 1,2-benzisoxazole-3-carboxamides derived from tertiary cycloalkylamines was synthesized and evaluated for affinity for serotonergic (5-HT 3 and 5-HT 4 ) and dopaminergic (D 2 ) receptors using radioligand binding assays. The majority of compounds displayed a very weak affinity for the studied neurotransmitter receptors. Only amides containing a conformationally rigid system retained a relative 5-HT 3 receptor affinity. The presence of a quinuclidine group affected receptor interaction more favorably than the tropane framework.

Synthesis and inhibitory effects on platelet aggregation of 3-(2-thienyl)- and 3-(1-imidazolyl)-1,2-benzisoxazole derivatives

A series of 3-(2-thienyl)- and 3-(1-imidazolyl)-1,2-benzisoxazoles as well as some isomeric benzoxazoles were synthesized and tested in vitro for their inhibitory effect on arachidonic acid-induced human platelet aggregation. The most active compound (7-methoxy-3-(2-thienyl)-1,2-benzisoxazole 5c) was nearly 20–30-fold more potent than acetylsalicylic acid in inhibiting platelet aggregation. Structure-activity relationships within the series are briefly discussed.

Synthesis and activities of a thienyl dihydropyridine series on intracellular calcium in a rat pituitary cell line (GH3/B6)

Summary The synthesis of a thienyl dihydropyridine series according to the Hantzsch method is described. The influence of these derivatives on intracellular calcium ([Ca + ]) in GH3 cells was evaluated in vitro using spectrofluorimetry with indol as Ca + f fluorescent probe. We compared their effects on [Ca + ]i and hormone release with those of nifedipine. The most active tested compounds on [Ca + ]i were those methylated on the 3-position of the thienyl ring (activity was about 75% of nifedipine). Interestingly, the most efficient compounds on [Ca + ]i were also the most efficient on hormone release.

Inhibitory Effect of Aryl Thienyl-Ketones and - Thioketones on Arachidonic Acid-induced Malondialdehyde Formation in Human Platelets: Biological Data and Molecular Modelling

A series of anti-thrombotic aryl thienyl-ketones and -thioketones was assayed in vitro for their inhibitory effect on malondialdehyde (MDA) production induced by arachidonic acid in human platelets. For several compounds MDA formation was strongly inhibited indicating that the anti-platelet target was situated on the cyclooxygenase pathway. A comparison between the inhibition constant Ki and the IC50 values revealed competitive inhibition kinetics. The molecular structure of one active compound was analysed by X-ray diffraction and theoretical calculations to provide information on its electronic and lipophilic properties.

Synthèse et activité anti-inflammatoire de (3,5-di-tert-butyl-4-hydroxybenzylidène) cyclanones et composés apparentés

Some (3,5-di-ert-butyl-4-hydroxybenzylidene) cyclanones were synthesized and evaluated for anti-inflammatory activity in carragenin-induced rat paw edema assay. These compounds are slightly less active than phenylbutazone. Their inhibitory effects in vitro on human platelet aggregation have been also examined. The present study shows that the inhibitor profile of the tested compounds on platelet aggregation induced by arachidonic acid (AA), collagen and adenosine diphosphate (ADP) bears similarly to that of acetylsalicylic acid. The free radical scavenging activity against 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical was measured by Electron Spin Resonance spectrometry. All the studied compounds scavenge the DPPH radical, dose dependently.