Synthesis and serotonergic activity of variously substituted (3-amido)phenylpiperazine derivatives and benzothiophene-4-piperazine derivatives: novel antagonists for the vascular 5-HT1B receptor.
Author(s)
Moloney, Greard P.
Garavelas, A.
Martin, Graeme R.
Maxwell, Miles
Glen, Robert C.
Griffith University Author(s)
Year published
2004
Metadata
Show full item recordAbstract
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 ...
View more >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.
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View more >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.
View less >
Journal Title
European Journal of Medicinal Chemistry
Volume
39
Issue
4
Publisher URI
Copyright Statement
© 2004 Elsevier. Please refer to the journal's website for access to the definitive, published version.
Subject
Medicinal and Biomolecular Chemistry
Organic Chemistry
Pharmacology and Pharmaceutical Sciences