Synthesis of aryloxyalkylamines as h5-HT1B agonists with potential analgesic activity

Abstract

Most h5-HT 1B serotonin subreceptors agonists bind with high affinity but low selectivity. Aryloxyalkylamines are a curious exception. In this investigation a new series of aryloxyalkylamines (4-7, 10, 11) was designed and synthesized in which the naphthyl moiety in propranolol (I) is replaced by substituted phenyl group; in addition the alkyl side-chain is ethyl or a-substituted ethyl, thus keeping the distance between O and N atoms unchanged from the case of II. For a number of the synthesized compounds the binding affinity at 5-HT 1B and 5-HT 1D was determined and some were found to bind with high affinity and selectivity compared with I, and with comparable affinity and selectivity to II. Analgesic activity of selected synthesized compounds was investigated on experimental animals and proved to be 66-100% that of aspirin. O NHCH(CH 3 ) 2 OH O NHCH 3 II I