96000-22-5Relevant academic research and scientific papers
1-Cinnamyl-4-(2-methoxyphenyl)piperazines: Synthesis, binding properties, and docking to dopamine (D2) and serotonin (5-HT1A) receptors
Penjisevic, Jelena,Sukalovic, Vladimir,Andric, Deana,Kostic-Rajacic, Sladjana,Soskic, Vukic,Roglic, Goran
, p. 456 - 465 (2008/12/21)
Clinical properties of atypical antipsychotics are based on their interaction with D2 dopamine receptor and serotonin 5-HT1A and 5-HT2A receptors. As a part of our research program on new antipsychotics, we synthesized various derivatives of 1-cinnamyl-4-(2- methoxyphenyl)piperazines, and evaluated their affinities for D2, 5-HT1A, 5-HT2A, and adrenergic (α1) receptors using radioligand-binding assays. In addition, we performed docking analysis using models for the D2 and 5-HT1A receptors. All compounds exhibited low to moderate affinity to 5-HT1A and 5-HT 2A receptors, high affinity to the D2 receptor and large variability in affinities for the α1 receptor. Docking analysis indicated that the binding to D2 and 5-HT1A receptors is based on (i) interaction between protonated N1 of the piperazine ring and various aspartate residues, (ii) hydrogen bonds between various moieties of the ligand and the residues of threonine, serine, histidine or tryptophane, and (iii) edge-to-face interactions of the aromatic ring of the arylpiperazine moiety with phenylalanine or tyrosine residues. Docking data for the D 2 receptor can account for the binding properties obtained in binding assays, suggesting that the model is reliable and robust. However, docking data for the 5-HT1A receptor cannot account for actual binding properties, suggesting that further refinement of the model is required.
Synthesis, modelling, and μ-opioid receptor affinity of N-3(9)-arylpropenyl-N-9(3)-propionyl-3,9-diazabicyclo[3.3.1]nonanes
Pinna,Murineddu,Curzu,Villa,Vianello,Borea,Gessi,Toma,Colombo,Cignarella
, p. 553 - 562 (2007/10/03)
A series of N-3-arylpropenyl-N-9-propionyl-3,9-diazabicyclo[3.3.1]nonanes (1a-g) and of reverted N-3-propionyl-N-9-arylpropenyl isomers (2a-g), as homologues of the previously reported analgesic 3,8-diazabicyclo[3.2.1]octanes (I-II), were synthesized and evaluated for the binding affinity towards opioid receptor subtypes μ, δ and κ. Compounds 1a-g and 2a-g exhibited a strong selective μ-affinity with Ki values in the nanomolar range, which favourably compared with those of I and II. In addition, contrary to the trend observed for DBO-I, II, the μ-affinity of series 2 is markedly higher than that of the isomeric series 1. This aspect was discussed on the basis of the conformational studies performed on DBN which allowed hypotheses on the mode of interaction of these compounds with the μ receptor.
