Synthesis of Aminoethyl-Substituted Piperidine Derivatives as σ1 Receptor Ligands with Antiproliferative Properties was written by Holtschulte, Catharina;Borgel, Frederik;Westphalinger, Stefanie;Schepmann, Dirk;Civenni, Gianluca;Laurini, Erik;Marson, Domenico;Catapano, Carlo V.;Pricl, Sabrina;Wuensch, Bernhard. And the article was included in ChemMedChem in 2022.SDS of cas: 33439-27-9 This article mentions the following:
A series of novel σ1 receptor ligands with a 4-(2-aminoethyl)piperidine scaffold I [ R1 = H,methyl, ethyl; R2 = benzylamino, cyclohexylmethylamino etc] were prepared and biol. evaluated. The underlying concept of project were the improvement of the lipophilic ligand efficiency of previously synthesized potent σ1 ligands. The key steps of the synthesis comprise the conjugate addition of phenylboronic acid at dihydropyridin-4(1H)-ones, homologation of the ketones and introduction of diverse amino moieties and piperidine N-substituents. 1-Methylpiperidines showed particular high σ1 receptor affinity and selectivity over the σ2 subtype, while piperidines with a proton, a tosyl moiety or an Et moiety exhibited considerably lower σ1 affinity. Mol. dynamics simulations with per-residue binding free energy deconvolution demonstrated that different interactions of the basic piperidine-N-atom and its substituents (or the cyclohexane ring) with the lipophilic binding pocket consisting of Leu105, Thr181, Leu182, Ala185, Leu186, Thr202 and Tyr206 were responsible for the different σ1 receptor affinities. Recorded logD7.4 and calculated clogP values of I [ R1 = H,methyl; R2 = benzylamino] indicated low lipophilicity and thus high lipophilic ligand efficiency. Piperidine I [ R1 = H; R2 = benzylamino] inhibited the growth of human non-small cell lung cancer cells A427 to a similar extent as the σ1 antagonist haloperidol. 1-Methylpiperidines I [ R1 = methyl; R2 = cyclohexylmethylamino, benzyl(methyl)amino, 4-phenylpiperazin-1-yl] showed stronger antiproliferative effects on androgen neg. human prostate cancer cells DU145 than the σ1 ligands NE100 and S1RA. In the experiment, the researchers used many compounds, for example, 1-Tosylpiperidin-4-one (cas: 33439-27-9SDS of cas: 33439-27-9).
1-Tosylpiperidin-4-one (cas: 33439-27-9) belongs to piperidine derivatives. Piperidine and its derivatives have become increasingly popular in many synthetic schemes. Some chemotherapeutic agents have piperidine moiety within their structure, foremost among them, vinblastine and raloxifene.SDS of cas: 33439-27-9
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem