| 15072840 |
Moloney GP, Garavelas A, Martin GR, Maxwell M, Glen RC: Synthesis and serotonergic activity of variously substituted (3-amido) phenylpiperazine derivatives and benzothiophene-4-piperazine derivatives: novel antagonists for the vascular 5-HT1B receptor. Eur J Med Chem. 2004 Apr;39(4):305-21.
The synthesis and vascular 5-HT (1B) 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-HT (1B) receptor of pK (B) > 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-HT (1B) receptor mediated agonist activity in the rabbit femoral artery) and competitive vascular 5-HT (1B) receptor antagonist. The affinity of compounds from these two series of compounds for the vascular 5-HT (1B) receptor is discussed as well as a proposed mode of binding to the receptor pharmacophore. |
115(1,2,2,5) |