Synthesis and serotonergic activity of variously substituted (3-amido)phenylpiperazine derivatives and benzothiophene-4-piperazine derivatives: novel antagonists for the vascular 5-HT1B receptor
- Resource Type
- Article
- Authors
- Moloney, Gerard P.; Garavelas, Agatha; Martin, Graeme R.; Maxwell, Miles; Glen, Robert C.
- Source
- European Journal of Medicinal Chemistry. Apr2004, Vol. 39 Issue 4, p305. 17p.
- Subject
- *THIOPHENES
*ANILINE
*ANGIOTENSINS
- Language
- ISSN
- 0223-5234
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 derivatives is described. Modifications to the amido linked sidechains of the 3-amidophenyl-piperazine derivatives and to the 2-sidechain of the 1-benzo[b]thiophene derivatives have been explored. Several compounds were identified which exhibited affinity at the vascular 5-HT1B receptor of pKB > 7.0. From the 3-amidophenyl-piperazine series, N-(4-(4-chlorophenyl)thiazol-2-yl-3-(4-methyl-1-piperazinyl)benzamide (30) and from the benzo[b]thiophene-4-piperazine series N-(2-ethylphenyl)-4-(4-methyl-1- piperazinyl)-1-benzo[b]thiophene-2-carboxamide (38) 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 compounds from these two series of compounds for the vascular 5-HT1B receptor is discussed as well as a proposed mode of binding to the receptor pharmacophore. [Copyright &y& Elsevier]