Modeling studies demonstrate that aryl piperazines (I), aryloxyalkylamines (II), phenylalkykamines (III) and indolylalkylamines (VI) may interact at 5-HT receptors in a similar manner. Examination of these structures (I-VI) reveals that all possess an aromatic moiety and terminal amine binding sites (Glennon et al., J Med Chem 32(8):1921-1926, 1989). In the present investigation a new series of aryloxyalkylamines (4, 5, 8, and 9) was designed and synthesized, in which the aromatic moiety is a phenyl group substituted at the 2,3-, 2,4-, 2,5-, or 2,6-positions by halogens and the terminal amine is N-methylpiperazine, or morpholine. In addition, the alkyl side chain is ethyl, or substituted ethyl at the a-or b-carbon by a methyl group. The length of the alkyl chain that separates the terminal amine from the ether oxygen atom of the aryloxy group is of major importance, and two-carbon chain appears optimal. The structures of the new compounds were assessed by microanalyses, IR, and NMR. The analgesic activity of selected compounds was performed on experimental animals and proved to be in the range of 85-100% relative to aspirin.

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

Die Umsetzung von 3‐Methyl‐ (Ia) oder 3‐Phenylpyrazolinon (Ib) mit den Sulfonylchloriden (II) führt zu den O‐Sulfonylverbindungen (III).