101620-08-0Relevant academic research and scientific papers
Hybrid approach for the design of highly affine and selective dopamine D3 receptor ligands using privileged scaffolds of biogenic amine GPCR ligands
Sasse, Britta C.,Mach, Ulrich R.,Leppaenen, Jukka,Calmels, Thierry,Stark, Holger
, p. 7258 - 7273 (2008/03/27)
A series of compounds containing privileged scaffolds of the known histamine H1 receptor antagonists cetirizine, mianserin, ketotifen, loratadine, and bamipine were synthesized for further optimization as ligands for the related biogenic amine binding dopamine D3 receptor. A pharmacological screening was carried out at dopamine D2 and D3 receptors. In the preliminary testing various ligands have shown moderate to high affinities for dopamine D3receptors, for example, N-(4-{4-[benzyl(phenyl)amino]piperidin-1-yl}butylnaphthalen-2-carboxamide (19a) (hD3 Ki = 0.3 nM; hD2 Ki = 703 nM), leading to a selectivity ratio of 2343.
Acrylamide derivatives as antiallergic agents. 2. Synthesis and structure-activity relationships of N-[4-[4-(diphenylmethyl)-1-piperazinyl]butyl]-3-(3-pyridyl)acrylamides
Nishikawa,Shindo,Ishii,Nakamura,Kon,Uno
, p. 583 - 593 (2007/10/02)
A new series of 3-(3-pyridyl)acrylamides 16, 17, 19, and 26, and 5-(3-pyridyl)-2,4-pentadienamides 20-25 were prepared and evaluated for their antiallergic activity. Several of these compounds exhibited more potent inhibitory activities than the parent compounds 1a [(E)-N-[4 [4-(diphenylmethyl)-1-piperazinyl]butyl]-3-(3-pyridyl)acrylamide] against the rat passive cutaneous anaphylaxis (PCA) reaction and the enzyme 5-lipoxygenase. Particularly, 4-[4-(diphenylmethyl)-1-piperazinyl]butyl]-3-(6-methyl-3-pyridyl)acrylamide (17p) showed an ED50 value of 3.3 mg/kg po in the rat PCA test, which was one-fifth of ketotifen and oxatomide. As compared with ketotifen and oxatomide, compound 17p (AL-3264) possessed a better balance of antiallergic properties due to inhibition of chemical mediator release, inhibition of 5-lipoxygenase, and antagonism of histamine.
