New substituted 1-(2,3-dihydrobenzo[1,4]dioxin-2-ylmethyl)piperidin-4-yl derivatives with alpha(2)-adrenoceptor antagonist activity

The emergence of a novel theory concerning the role of noradrenaline in the progression and the treatment of neurodegenerative diseases such as Parkin son's and Alzheimer's diseases has provided a new impetus toward the discov ery of novel compounds acting at alpha(2)-adrenoceptors. A series of substi tuted 1-(2,3-dihydrobenzo[1,4]dioxin-2-ylmethyl) piperidin-4-yl derivatives bearing an amide, urea, or imidazolidinone moiety was studied. Some member s of this series of compounds proved to be potent alpha(2)-adrenoceptor ant agonists with good selectivity versus alpha(1)-adrenergic and D-2-dopamine receptors. Particular emphasis is given to compound 33g which displays pote nt alpha(2)-adrenoceptor binding affinity in vitro and central effects in v ivo following oral administration.