Spadoni, Gilberto published the artcileTowards the development of 5-HT7 ligands combining serotonin-like and arylpiperazine moieties, Safety of 1-Biphenyl-4-yl-piperazine, the publication is European Journal of Medicinal Chemistry (2014), 8-35, database is CAplus and MEDLINE.
Many known 5-HT7 ligands contain either a serotonin-like or an arylpiperazine structure that, in published SAR studies, are generally supposed to bind the same receptor pocket. Conversely, the authors explored the hypothesis that two such moieties can coexist in the same ligand, binding to different pockets. The authors thus designed and synthesized a set of compounds including both a 5-hydroxyindol-3-ylethyl and a 1-arylpiperazine moieties connected by a short linker, e.g. I [R1 = HO, NH2, Cl, etc.; R2 = Ph, α-naphthyl, β-naphthyl, etc.; X = CH2, O, NH, etc.; Y = (CH2)n; n = 2, 3, 4, 5, 6]. The compounds were tested for their affinity for human 5-HT7 serotonin receptor. The authors further prepared a novel series of 5-HT7 ligands, where the 5-hydroxyindol-3-ylethyl moiety was bioisosterically replaced by a 3-hydroxyanilinoalkyl one. Among the newly synthesized compounds, potent ligands at the 5-HT7 receptor, behaving as antagonists in functional tests, were identified, even if they showed limited subtype selectivity. Docking studies within a model of the 5-HT7 receptor showed that the binding site can actually accommodate both moieties, with the serotonin-like one in the putative orthosteric site and the arylpiperazine one occupying an accessory pocket. The present results demonstrate that it is possible to devise and develop new 5-HT7 ligands merging two privileged structures in the same mol.
European Journal of Medicinal Chemistry published new progress about 180698-19-5. 180698-19-5 belongs to piperazines, auxiliary class Piperazine,Benzene, name is 1-Biphenyl-4-yl-piperazine, and the molecular formula is C6H12N2O, Safety of 1-Biphenyl-4-yl-piperazine.
Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics