Main Article Content
Abstract
A series of new 3,4-dihydroquinolin-2(1H)-one analogs of aripiprazole structural similarity compound was synthesized to explore the influence of structural features-replacement of 2,3-dichlorophenyl-4-piperazine/ diazepane moiety with 3-methyl-2,7-diphenyl-1,4-diazepan-5-one. All the synthesized compounds are characterized by elemental analysis, FT-IR, 1H NMR, 13C NMR, HSQC (2D NMR) and mass spectrometry. All the multitarget ligands have been docked against, human A2A Adenosine receptor and human β2-Adrenergic G-protein coupled receptor (GPCR), both receptor and ligand interaction shows an excellent dock score. Adsorption, distribution, metabolism and extraction (ADME) properties were also evaluated in the desirable range. Finally these compounds have orally drug-likeness property. In this event screening was performed for the neuroleptic activity of the synthesized compounds with different anti-psychotic animal models.
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References
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References
P. Tyrer and T. Kendall, Lancet, 373, 4 (2009); https://doi.org/10.1016/S0140-6736(08)61765-1.
B.L. Roth, D.J. Sheffler and W.K. Kroeze, Nat. Rev. Drug Discov., 3, 353 (2004); https://doi.org/10.1038/nrd1346.
B. Bang-Andersen, T. Ruhland, M. Jørgensen, G. Smith, K. Frederiksen, K.G. Jensen, H. Zhong, S.M. Nielsen, S. Hogg, A. Mørk and T.B. Stensbøl, J. Med. Chem., 54, 3206 (2011); https://doi.org/10.1021/jm101459g.
G. Sarkisyan, A.J. Roberts and P.B. Hedlund, Behav. Brain Res., 209, 99 (2010); https://doi.org/10.1016/j.bbr.2010.01.022.
A. DeLeon, N.C. Patel and M. Lynn Crismon, Clin. Ther., 26, 649 (2004); https://doi.org/10.1016/S0149-2918(04)90066-5.
Y. Tadori, T. Miwa, K. Tottori, K.D. Burris, A. Stark, T. Mori and T. Kikuchi, Eur. J. Pharmacol., 515, 10 (2005); https://doi.org/10.1016/j.ejphar.2005.02.051.
B. Kiss, A. Horvath, Z. Nemethy, E. Schmidt, I. Laszlovszky, G. Bugovics, K. Fazekas, K. Hornok, S. Orosz, I. Gyertyan, E. Agai-Csongor, G. Domany, K. Tihanyi, N. Adham and Z. Szombathelyi, J. Pharmacol. Exp. Ther., 333, 328 (2010); https://doi.org/10.1124/jpet.109.160432.
A. Fitton and R.C. Heel, Drugs, 40, 722 (1990); https://doi.org/10.2165/00003495-199040050-00007.
J.T. Schwartz and A.W. Brotman, Drugs, 44, 981 (1992); https://doi.org/10.2165/00003495-199244060-00007.
R. Rosenheck, J. Cramer, W. Xu, J. Thomas, W. Henderson, L. Frisman, C. Fye and D.N. Charney, N. Engl. J. Med., 337, 809 (1997); https://doi.org/10.1056/NEJM199709183371202.
D.A. Shapiro, S. Renock, E. Arrington, L.A. Chiodo, L.X. Liu, D.R. Sibley, B.L. Roth and R. Mailman, Neuropsychopharmacology, 28, 1400 (2003); https://doi.org/10.1038/sj.npp.1300203.
S.M. Stahl, J. Clin. Psychiatry, 60(Suppl.10), 31 (1999).
C.R. Noller and V. Baliah, J. Chem. Soc., 70, 3853 (1948); https://doi.org/10.1021/ja01191a092.
S.K. Kulkarni and P.C. Dandia, Ind. J. Med. Res., 63, 462 (1975).
R. Corbett, F. Camacho, S. Woods, L.L. Kerman, R.J. Fishkin, K. Brooks and R.W. Dunn, Psychopharmacology, 120, 67 (1995); https://doi.org/10.1007/BF02246146.
S. Matthysse, Prog. Brain Res., 65, 259 (1986); https://doi.org/10.1016/S0079-6123(08)60655-X.
C.A. Lipinski, F. Lombardo, B.W. Dominy and P.J. Feeney, Adv. Drug Deliv. Rev., 46, 3 (2001); https://doi.org/10.1016/S0169-409X(00)00129-0.
C.A. Lipinski, F. Lombardo, B.W. Dominy and P.J. Feeney, Adv. Drug Deliv. Rev., 23, 3 (1997); https://doi.org/10.1016/S0169-409X(96)00423-1.
Qikprop, version 3.5, Schrodinger, LLC, New York (2012).
J.J. Lu, K. Crimin, J.T. Goodwin, P. Crivori, C. Orrenius, L. Xing, P.J. Tandler, T.J. Vidmar, B.M.E. Amore, A.G. Wilson, P.F.W. Stouten and P.S. Burton, J. Med. Chem., 47, 6104 (2004); https://doi.org/10.1021/jm0306529.
P. Artursson, K. Palm and K. Luthman, Adv. Drug Deliv. Rev., 46, 27 (2001); https://doi.org/10.1016/S0169-409X(00)00128-9.