Pyridinylpiperazines, a new class of selective .alpha.2-adrenoceptor antagonists

Abstract

A series of 1-(2-pyridinyl)piperazine derivatives was synthesized and evaluated for adrenergic activity. In vitro activity was assessed through the antagonism of clonidine's effect in the rat, isolated, field-stimulated vas deferens and by the displacement of [3H]clonidine from membrane binding sites of calf cerebral cortex. Antagonism of clonidine-induced mydriasis in the rat was used as an in vivo assay. Several members of the series proved to be potent, selective alpha 2-adrenoceptor antagonists. 1-(3-Fluoro-2-pyridinyl)piperazine was more potent than either yohimbine or rauwolscine in displacement of [3H]clonidine and had a higher affinity for this binding site (alpha 2) than for the [3H]prazosin site (alpha 1). In vivo, the 3-F derivative was more potent than the reference standards in reversing clonidine-induced mydriasis. None of the members of this series was more selective or potent than rauwolscine in antagonizing clonidine in the rat vas deferens.

Third‐generation antidepressants

“…6). 134,135 None of these a,-adrenoceptor antagonists seem to have undergone evaluation in depressed patients.…”

N-Dealkylation of Arylpiperazine Derivatives: Disposition and Metabolism of the 1-Aryl-Piperazines Formed

“…Some derivatives are agonists at certain 5-HT receptors but antagonists at others, as exemplified again by mClPP which has agonistic activity at the human 5-HT 2C subtype but antagonist action at 5-HT 2B and 5-HT 7 receptors [6][7]. Some have more affinity and selectivity for other neurotransmitter receptors and systems; 1-(2-pyrimidinyl)-piperazine (PmP or 1-PP) and 1-(2-pyridinyl)piperazine (PdP) and its derivatives, for example, bind with high affinity to alpha 2 sites, acting in vivo as alpha 2 -adrenoceptor antagonists in man and animals [8][9][10][11].…”

Microwave-Assisted Amination from Aryl Triflates without Base and Catalyst

“…Anilines are very important motifs that have found wide application in fluorescence probes, pharmaceutical and agrochemical industry, photography systems, electronic devices, and natural materials production . Traditional nucleophilic aromatic substitution reactions (S N Ar) of N - nucleophiles are limited to only activated aromatic substrates . The synthesis of anilines by Cu-mediated Ullmann condensation often suffers from severe reaction conditions …”