[Benzoxazolinone phenylethanolamine antagonists of adrenergic receptors. A chemical and pharmacodynamic study]. / Phényléthanolamines benzoxazolinoniques antagonistes des récepteurs adrénergiques. Etude chimique et pharmacodynamique.

Benzoxazolinone can be considered as a bioisosteric analogue of pyrocatechol. This concept has led to the synthesis of benzoxazolinonic phenylethanolamines. The pharmacological study shows that these compounds possess an affinity for adrenergic receptors. Compound (XXXIV), the most interesting, is a competitive alpha and beta adrenergic antagonist which has been studied for antihypertensive activity.

Chemical and pharmacological studies of 2-(amino-methyl)acrylophenones.

The structure-activity relationships of nine products of the acrylophenone family have been studied. In a previous report 2-(4-methyl-1-piperazinylmethyl)acrylophenone was shown to be an antimicrotubular drug. The effects of these drugs on the bovine brain tubulin polymerization were determined by a turbidimetric assay. The median inhibitory concentrations (ID50) ranged from 1.5 X 10(-5) to 5 X 10(-5) mol/l. Their action on the inhibition of 3H-colchicine binding to tubulin was determined by DEAE (diethylaminoethyl)cellulose filter assay. These compounds are weak inhibitors of colchicine binding. Pharmacological studies of these drugs revealed a strong inhibition of the human ADP-induced platelet aggregation. Moreover, they markedly decreased the serum cholesterol, triglycerides and phospholipids levels of rats after injection of Triton WR 1339 (4-(1,1,3,3-tetramethylbutyl)phenol polymer with formaldehyde and oxirane). They inhibited Candida albicans, Penicillium notatum and Aspergillus versicolor growth. Thus, these nine compounds possess interesting pharmacological properties which are very likely to be related to the acrylic moiety of the molecules.

[Synthesis and pharmacologic study of 6-(amino-2 ethyl) benzoxazolinones]. / Synthèse et étude pharmacologique d'(amino-2 éthyl)-6 benzoxazolinones.

Reaction of various amines on 6-(2-bromoethyl)benzoxazolinone or its N-methylated derivative provided eleven new 6-substituted aminoalkyl analogues. In a pharmacological evaluation, several compounds bearing an arylpiperazinic moiety were found to possess significant effects on arterial blood pressure and on the central nervous system; two of them showed interesting analgesic activity.

Pharmacological study of nine antimicrotubular drugs with acrylophenone structure on Triton WR 1339-induced hyperlipidemia in rats.

Nine (amino-methyl)-2 acrylophenone derivatives having in vitro antimicrotubular activities very similar to those of colchicine are tested on Triton WR 1339-induced hyperlipidemia in rats. By producing a disorganization of the microtubular system, these drugs reduce the lipoprotein secretory process from hepatocytes, and more particularly the triglyceride-rich VLDL secretory process, such that the serum triglyceride, cholesterol and phospholipid levels are decreased. On the other hand, HDL-cholesterol and HDL-phospholipids are increased in a significant manner. Other studies show that serum apoprotein B levels are decreased while serum apoprotein A1 levels are increased. These results are interesting since atherogenous risk is now known to be dyslipemia-related, and is not the same according to the fact that lipids are bound to one or another lipoprotein. Among the four most effective compounds (5,7,8 and 9) three of them possess a methoxy group on the aromatic ring, which seems to distinguish that series from the other two.