Open Access Peer-reviewed

Field Alignment Studies on a Series of Piperazine Based CNS Active Agents

Alka Bali
University Institute of Pharmaceutical Sciences, UGC Center of Advanced Study, Chandigarh, Panjab University, India
American Journal of Pharmacological Sciences. 2013, 1(1), 1-5. DOI: 10.12691/ajps-1-1-1
Published online: August 25, 2017


Field alignment studies have been carried out on a series of piperazine based agent with central nervous systemactivity with respect to a set of standard atypical antipsychotics. This alignment method takes into account the local extrema of electrostatic, vander Waals and hydrophobic potentials of the molecule termed as 'field points' or 'extended pharmacophores' and aligns the molecules based on the relative positioning of these points. The standard drugs taken for the study included the dibenzodiazepine derivative clozapine and some other drugs with extended chain structure ketanserin, ziprasidone and risperidone. The three dimensional similarity of the molecules to the standard drugs based on their field scores and shape scores has been computed. The results obtained were found to agree with the physicochemical similarity of the compounds reported earlier.


Molecular Fields, Field Similarity, Piperazine, Field Points, 3D Similarity, Shape Similarity
[1]  Kubinyi, H,“Similarity and dissimilarity: A medicinal chemist’s view”,Perspectives in Drug Discovery and Design, 9, 225-252, Jan. 1998.View Article
[2]  Flower, D.R,“On the properties of bit string-based measures of chemical similarity”, Journal of Chemical Informationand Computer Science, 38, 379-386, May 1998.View Article
[3]  Holliday, J.D., Hu, C-Y., Willett, P,“Grouping of coefficients for the calculation of intermolecular similarity and dissimilarity using 2D fragment bit-strings”,Combinatorial Chemistry and High-Throughput Screening, 5, 155-166, Mar. 2002.View Article  PubMed
[4]  Mestres, J., Rohrer, D.C., Maggiora, G.M, “A molecular-field-based similarity study of non-nucleoside HIV-1 reverse transcriptase inhibitors. 2. The relationship between alignment solutions obtained from conformationally rigid and flexible matching”, Journal of Computer Aided Molecular Design, 14, 39-51, Jan. 2000.View Article  PubMed
[5]  Mestres, J., Rohrer, D.C., Maggiora, G.M, “A molecular field based similarity study of non-nucleoside HIV-1 reverse transcriptase inhibitors”,Journal of Computer Aided Molecular Design, 13, 79-93, Jan. 1999.View Article  PubMed
[6]  Thorner, D.A., Wild, D.J., Willett, P., Wright, P.M, “Similarity searching in files of three-dimensional chemical structures:  Flexible field-based searching of molecular electrostatic potentials”,Journal of Chemical Information and Computer Science, 36, 900-908, Jul.1996.View Article
[7]  Geneste, H., Backfisch, G., Braje, W., Delzer, J., Haupt, A., Hutchins, C.W,“Synthesis and SAR of highly potent and selective dopamine D3-receptor antagonists: Quinolin(di)one and benzazepin(di)one derivatives”,Bioorganic and Medicinal Chemistry Letters, 16, 658-662, Feb. 2006.View Article
[8]  Masaguer, F.C., Ravina, E., Fontenla, J.A., Brea, J., Tristan, J., Loza, M.I,“Butyrophenone analogues in the carbazole series as potential atypical antipsychotics: Synthesis and determination of affinities at D2, 5-HT2A, 5-HT2B and 5-HT2C receptors”,EuropeanJournal of Medicinal Chemistry, 35, 83-95, Jan. 2000.View Article
[9]  Reitz, A.B., Bennett, D.J., Blum, P.S., Codd, E.E., Maryanoff, C.A., Ortegon, M.E,“A new arylpiperazine antipsychotic with high D2/D3/5-HT1a/α1 adrenergic affinity and a low potential for extrapyramidal effects”,Journal of Medicinal Chemistry, 37, 1060-1062, Apr. 1994.View Article  PubMed
[10]  Cole, D.C., Ellingboe, J.W., Lennox, W.J., Mazandarani, H., Smith, D.L., Stock, J.R,“N1-arylsulfonyl-3-(1, 2, 3, 6-tetrahydropyridin-4-yl)-1H-indole derivatives are potent and selective 5-HT6 receptor antagonists”,Bioorganic and Medicinal Chemistry Letters, 15, 379-383, Jan. 2005.View Article  PubMed
[11]  Xu, R., Lever, J.R., Lever, S.Z, “Synthesis and in vitro evaluation of tetrahydroisoquinolinylbenzamides as ligands for σ receptors”, Bioorganic and Medicinal Chemistry Letters, 17, 2594-2597, May 2007.View Article  PubMed
[12]  Zhao, H., Thurkauf, A., He, X., Hodgetts, K., Zhang, X., Rachwal, S, “Indoline and piperazinecontaining derivatives as a novel class of mixed D2/D4 receptor antagonists. Part 1: Identification and structure–activity relationships”, Bioorganic and Medicinal Chemistry Letters, 12, 3105-3109, Nov. 2002.View Article
[13]  Bali, A., Sharma, K., Bhalla, A., Bala, S., Reddy, D., Singh, A,“Synthesis, evaluation and computational studies on a series of acetophenone based 1-(aryloxypropyl)-4-(chloroaryl) piperazines as potential atypical antipsychotics”,European Journal of Medicinal Chemistry, 45, 2656-2662, Jun. 2010.View Article  PubMed