ORIGINAL RESEARCH Synthesis of aryloxyalkylamines as h5-HT 1B agonists with potential analgesic activity Abdulkhader M. Ismaiel Laila M. Gad Salah A. Ghareib Faida H. Bamanie Mohamed A. Moustafa Received: 21 January 2007 / Accepted: 30 January 2009 Ó Birkha ¨user Boston 2009 Abstract Most h5-HT 1B serotonin subreceptors agonists bind with high affinity but low selectivity. Aryloxyalkylamines are a curious exception. In this investiga- tion 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 deter- mined 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 Keywords Aryloxyalkylamines Á h5-HT 1B Serotonin subreceptors agonists Á Binding affinity Á Analgesic activity A. M. Ismaiel Á L. M. Gad (&) Á F. H. Bamanie Á M. A. Moustafa Pharmaceutical Chemistry Department, Faculty of Pharmacy, King Abdulaziz University, P.O. 80260, Jeddah 21589, KSA e-mail: lgad@kau.edu.sa; gad_laila@yahoo.com S. A. Ghareib Pharmacology and Toxicology Department, Faculty of Pharmacy, King Abdulaziz University, P.O. 80260, Jeddah 21589, KSA Med Chem Res DOI 10.1007/s00044-009-9164-1 MEDICINAL CHEMISTR Y RESEARCH