σ Ligands with Subnanomolar Affinity and Preference for the σ2 Binding Site. 1. 3-(ω-Aminoalkyl)-1H-indoles was written by Perregaard, Jens;Moltzen, Ejner K.;Meier, Eddi;Sanchez, Connie. And the article was included in Journal of Medicinal Chemistry in 1995.SDS of cas: 58333-75-8 This article mentions the following:
A series of 4-(1H-indol-3-yl)-1-butyl-substituted 4-phenylpiperidines, 4-phenyl-1,2,3,6-tetrahydropyridines, and 4-phenylpiperazines was synthesized. The Ph group was optionally substituted with 4-fluoro or 2-methoxy substituents. High affinity for both σ1 and σ2 binding sites was achieved with these compounds Addnl., these compounds had relatively high affinity for serotonin 5-HT1A and 5-HT2A, dopamine D2, and adrenergic α1 receptors. Introduction of a 4-fluorophenyl substituent at the indole nitrogen atom rendered very selective σ2 ligands with subnanomolar affinity for the σ2 binding site. The prototype of such a compound was I. This compound had the following binding affinities: IC50 (σ1) = 16 nM, IC50 (σ2) = 0.27 nM, IC50 (5-HT1A) = 22 000 nM, IC50 (5-HT2A) = 270 nM, IC50 (D2) = 4200 nM, IC50 (α1) = 220 nM. Spiro-joining of the Ph and the piperidine rings into a spiro[isobenzofuran-1(3H),4′-piperidine] ring system resulted in even more selective compounds Variations of the 1-substituent at the indole and of the chain length of the alkylene spacer group were studied. The optimal compound was the spiro analog of I. This compound (II) had the binding affinities: IC50 (σ1) = 17 nM, IC50 (σ2) = 0.12 nM, IC50 (5-HT1A) = 21 000 nM, IC50 (5-HT2A) = 2000 nM, IC50 (D2) = 800 nM, IC50 (α1) = 330 nM. However, the most selective σ2 vs. σ1 ligand was the tropane derivative (III). This compound had the following binding affinities: IC50 (σ1) = 1200 nM, IC50 (σ2) = 2.5 nM. Potent anxiolytic activity in the black/white box exploration test in rats was found with the two most prominent σ2 ligands Lu 29-253 and Lu 28-179. Good penetration into the CNS was documented both after s.c. and peroral administration of Lu 28-179 by ex vivo binding studies. Long duration of action was demonstrated both in ex vivo binding (T1/2 ∼ 20 h) and in the black/white box exploration test. In the experiment, the researchers used many compounds, for example, 4-(2-Methoxyphenyl)piperidine (cas: 58333-75-8SDS of cas: 58333-75-8).
4-(2-Methoxyphenyl)piperidine (cas: 58333-75-8) belongs to piperidine derivatives. Piperidine is a metabolite of cadaverine, a polyamine found in the human intestine. Fluorinated piperidines are also the subject of continued interest in medicinal chemistry, for example in the synthesis of selective dipeptidyl peptidase II (DPP II) inhibitors. Piperidine derivatives are also used in solid-phase peptide synthesis (SPPS) and many degradation reactions.SDS of cas: 58333-75-8
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem