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Issue 19, 1999
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Synthesis and serotonergic activity of 2-oxadiazolyl-5-substituted-N,N-dimethyltryptamines: novel antagonists for the vascular 5-HT1B-like receptor

Abstract

The synthesis and vascular 5-HT1B-like receptor activity of a novel series of 2-oxadiazolyl-5-substituted tryptamine derivatives 2 is described. Modifications to the 2-oxadiazolyl group R1, the heterocycle R2 and the length of the linking chain (n) have been explored. Several compounds were identified which exhibited moderate 5-HT1B-like receptor affinity. In particular, 2-(3-ethyl-1,2,4-oxadiazol-5-yl)-3-[2-(dimethylamino)ethyl]-5-[(4,4-dimethyl-2,5-dioxoimidazolidin-1-yl)methyl]-1H-indole (20) in which n = 1 had a pKB = 7.23 at the 5-HT1B-like receptor and >60 fold selectivity over α1-adrenoceptor affinity. This contrasts with the higher homologue derivatives such as 10 and 11 where n = 2 which exhibited decreased potency and selectivity for the 5-HT1B-like receptor. The 2-oxadiazolyl-5-substituted-N,N-dimethyltryptamine derivatives were found to be silent (as judged by the inability of angiotensin II to unmask 5-HT1B-like receptor mediated agonist activity in the rabbit femoral artery) and competitive 5-HT1B-like receptor antagonists with half lives of up to 1.5 hours in dog plasma and with good oral bioavailability.

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Article information


J. Chem. Soc., Perkin Trans. 1, 1999, 2725-2733
Article type
Paper

Synthesis and serotonergic activity of 2-oxadiazolyl-5-substituted-N,N-dimethyltryptamines: novel antagonists for the vascular 5-HT1B-like receptor

G. P. Moloney, G. R. Martin, N. Mathews, S. MacLennan, S. Dodsworth, P. Yih Sang, C. Knight, M. Maxwell and R. C. Glen, J. Chem. Soc., Perkin Trans. 1, 1999, 2725
DOI: 10.1039/A903325D

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