Synthesis and serotonergic activity of variously substituted (3-amido)phenylpiperazine derivatives and benzothiophene-4-piperazine derivatives: novel antagonists for the vascular 5-HT1B receptor.
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The synthesis and vascular 5-HT1B receptor activity of a novel series of substituted 3-amido phenylpiperazine and 4-(4-methyl-1-piperazinyl)-1-benzo[b]thiophene derivs. is described. Modifications to the amido linked sidechains of the 3-amidophenyl piperazine derivs. and to the 2-side-chain of the 1-benzo[b]thiophene derivs. have been explored. Several compds. were identified which exhibited affinity at the vascular 5-HT1B receptor of pKB > 7.0. From the 3-amidophenyl-piperazine series, N-[5-(4-chlorophenyl)-2-thiazolyl]-3-(4-methyl-1-piperazinyl)benzamide (I) and from the benzo[b]thiophene-4-piperazine series N-(2-ethylphenyl)-4-(4-methyl-1-piperazinyl)benzo[b]thiophene-2-carboxamide (II) were identified as a highly potent, silent (as judged by the inability of angiotensin II to unmask 5-HT1B receptor mediated agonist activity in the rabbit femoral artery) and competitive vascular 5-HT1B receptor antagonist. The affinity of compds. from these two series of compds. for the vascular 5-HT1B receptor is discussed as well as a proposed mode of binding to the receptor pharmacophore.
European Journal of Medicinal Chemistry
© 2004 Elsevier. Please refer to the journal's website for access to the definitive, published version.