Design and synthesis of substituted compounds containing the 1, 4-benzodioxin subunit. New potential calcium antagonists.

New compounds possessing 1,4-benzodioxin or its saturated analogous heterocyclic system were synthesized and tested for calcium antagonist activity. Biological differences were seen between the different modifications applied. These compounds have been shown to be representative of a novel series of calcium channel antagonists.

New substituted 1,4-benzoxazine derivatives with potential intracellular calcium activity.

Substituted 1,4-benzoxazines bearing an amino side chain at the 2-position were prepared and were found to have a moderate activity on intracellular calcium. Of the compounds studied it was found that those which possess a homoveratrylamino moiety exhibited superior potency. The chain length and the nature of the amine (4-fluorophenylpiperazine, 4-fluorobenzhydryloxyethylamine, N-substituted homoveratrylamine) is discussed.

In vitro calcium antagonistic and antioxidant effects of Org 13061 and its enantiomers, new potential antiatherosclerotic compounds.

The calcium antagonistic and antioxidant properties of a new potential antiatherosclerotic agent, Org 13061 were compared with those of its (-) and (+) enantiomers (Org 13471 and Org 13581) In vitro and with appropriate reference drugs. Org 13061 antagonized contractions induced by potassium in rabbit aortic rings with an IC50 value of 0.50 microM and reduced the maximum rate of phase 0 depolarization (Vmax) of the 'slow' calcium-mediated transmembrane action potentials in cardiac tissue (IC25 = 0.

Effects of bepridil and of its quaternary derivative on rat tail artery.

The effects of bepridil and its quaternary ammonium derivative (BN+) were compared, showing that: (i) both drugs inhibited K+-induced contractions with similar time courses and potencies, (ii) bepridil blocked the tonic but not the phasic component of contractions elicited by noradrenaline, whereas BN+ had no effect on noradrenaline-elicited contractions. These results, and the relative insensitivity of skinned taenia caeci to bepridil, suggest that this drug and BN+ do not act directly on contractile proteins but affect K+- and noradrenaline-induced calcium channel activities differentially.

[Benzoxazolinone phenylethanolamine antagonists of adrenergic receptors. A chemical and pharmacodynamic study].

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.