14088-83-6Relevant articles and documents
Inhibitors of the glycine transporter type-2 (GlyT-2): synthesis and biological activity of benzoylpiperidine derivatives.
Wolin, Ronald L,Santillan Jr., Alejandro,Tang, Liu,Huang, Charles,Jiang, Xiaoxia,Lovenberg, Timothy W
, p. 4511 - 4532 (2007/10/03)
A series of benzoylpiperidine analogs related to 4a was prepared, and their ability to inhibit the uptake of [(14)C]-glycine in COS7 cells transfected with human glycine transporter type-2 (GlyT-2) was evaluated. Small structural changes to the benzoylpiperidine region of the molecule led to a significant decrease in GlyT-2 inhibitory activity. In contrast, the distal aryl ring was more tolerant to functional group modifications and could accommodate a variety of substitutes at the C-2 or C-3 positions. Comparable activities to 4a were obtained by replacing the anilino nitrogen with an ether linkage 27 or by exchanging the isopropoxy ether moiety with an isopropyl amino group 15. A distinct preference for a 2-carbon tether (n=1) was observed relative to the corresponding 3-carbon homolog (n=2).
Effect of modifications of the alkylpiperazine moiety of trazodone on 5HT(2A) and α1 receptor binding affinity
Giannangeli, Marilena,Cazzolla, Nicola,Luparini, Maria Rita,Magnani, Maurizio,Mabilia, Massimo,Picconi, Giuseppe,Tomaselli, Mauro,Baiocchi, Leandro
, p. 336 - 345 (2007/10/03)
A series of triazolopyridine derivatives (compounds 2a-1) were synthesized in order to explore the effect of modifications of the alkylpiperazine moiety of trazodone (fragment A) on binding affinity for 5HT(2A) and α1 receptors. All of the synthesized compounds show a decrease of affinity for both 5HT(2A) and α1 receptors, as compared to trazodone, with the exception of compounds 2b,c which bear a methyl group in an α position to the aliphatic nitrogen atom N1. These compounds showed a decrease of affinity only for the α1 receptor. The stereochemical influence of the piperazine moiety of compound 2c was also evaluated. Enantiomer (S)- 2c showed the most significant differences between 5HT(2A) and α1 receptor affinity (IC50 values) and among the corresponding functional properties (pA2 values). Since (S)-2c cannot generate the metabolite 4-(3- chlorophenyl)piperazine this product was selected for further pharmacological studies.
The Use of 2-Oxazolidinones as Latent Aziridine Equivalents. 2. Aminoethylation of Aromatic Amines, Phenols, and Thiophenols
Poindexter, Graham S.,Owens, Donald A.,Dolan, Peter L.,Woo, Edmund
, p. 6257 - 6265 (2007/10/02)
The utility of 2-oxazolidinones 1 as latent, carboxylated aziridine functionalities was examined.Reaction of 2-oxazolidinone (1a), 3-methyl2-oxazolidinone (1b), 3-(phenylmethyl)-2-oxazolidinone (1c), 3-phenyl-2-oxazolidinone (1d) 4,4-dimethyl-2-oxazolidinone (1e), and 5-ethyl-2-oxazolidinone (1f) with aromatic amine salts, phenol, or thiophenols at elevated temperatures (> 130 deg C) afforded aminoethylated adducts.The aminoethylation occurred with concomitant loss of carbon dioxide to furnish variously substituted N-aryl-1,2-ethanediamines 4, 1-(2-phenoxyethyl)-2-imidazolidinone (8), or 2-(arylthio)ethanamines 9 on reactions of 1 with aromatic amine salts, phenol, and thiophenols, respectively.Imidazolidinone 8 is believed to be a secondary reaction product resulting from the condensation of the initially formed 2-phenoxyethanamine with starting oxazolidinone 1a.The aminoethylation reaction did not proceed with aliphatic amine hydrochlorides or alkyl mercaptans.Preliminary mechanistic pathways for these ring openings were also investigated employing a specific, C-5 deuterium-labeled oxazolidinone 1b-d2.Ring-opening experiments of 1b-d2 with N-methylaniline hydrochloride suggest reaction can occur through either a dioxazolinium 5 and/or 5 intermediate.In contrast, reaction of 1b-d2 with thiophenol suggests ring-opening to proceed only via the dioxazolinium pathway.
