Indoline Analogues of Idazoxan: Potent α2-Antagonists and α1-Agonists

Article abstract of DOI:10.1021/jm00400a009

The synthesis and α-adrenergic activity of a series of substituted 2-imidazolinylindolines are described.Substitution in the indoline ring generated compounds with a spectrum of adrenoceptor antagonist/agonist profiles that proved sensitive to both the nature and position of the substituent.Many of the derivatives possess greater presynaptic antagonist potency that the corresponding benzodioxan 1, dihydrobenzofuran 2, and indan 3 analogues; however, this α₂-antagonism is often accompanied by α₁-agonist activity.It was not possible to separate α₂-antagonist from α₁-agonist properties in this series.Compounds of most interest proved to be the N-ethyl 6, 5-chloro-N-methyl 18 and 5-chloro-N-ethyl 23 derivatives, all being potent α₂-antagonists and α₁-agonists.Substitution at the 4- and 7-position of the indoline ring generally gave compounds with nonselective agonist properties.