PHENOLIC DERIVATIVES OF NO-N,N-DIPROPYL-1,2,3,4-TETRAHYDRONAPHTH-2-YLAMINE - STRUCTURAL HYBRIDS OF 2-AMINOTETRALIN-DERIVED AND PHENYLCYCLOPROPYLAMINE-DERIVED 5-HT(1A)-RECEPTOR AGONISTS

Three phenolic derivatives of 1,2-methano-N,N-dipropyl- 1,2,3,4-tetrah ydronaphth-2-ylamine 6-8 were synthesized as structural hybrids of the potent 5-HT1A-receptor agonist 8-OH-DPAT 1 and 2 related phenolic phe nylcyclopropylamines 4 and 5. The new compounds were assayed for 5-HT1 A-receptor affinity and efficacy in vitro. Hybrids 6 and 7 were consid ered to be inactive but 8 had a K(i) value of 130 nM for [H-3]-8-OH-DP AT labelled 5-HT1A-receptors and produced an inhibition of the cAMP-pr oduction in the VIP-stimulated adenylyl cyclase assay. Thus, 8 is able to bind to and stimulate 5-HT1A-receptors. The results are discussed in relation to a previously described 3-D model for 5-HT1A-receptor ag onists.