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Research Article

Arylpiperazinylalkyl derivatives of 8-amino-1,3-dimethylpurine-2,6-dione as novel multitarget 5-HT/D receptor agents with potential antipsychotic activity

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Pages 1048-1062 | Received 16 Jun 2015, Accepted 20 Jul 2015, Published online: 25 Sep 2015

References

  • Stahl S. Describing an atypical antipsychotic: receptor binding and its role in pathophysiology. Prim Care Companion J Clin Psychiatry 2003;5:9–13
  • Roth BL, Sheffler D, Potkin SG. Atypical antipsychotic drug actions: unitary or multiple mechanism for ‘atypicality’? Clin Neurol Res 2003;3:108–17
  • Divac N, Prostran M, Jakovcevski I, Cerovac N. Second-generation antipsychotics and extrapyramidal adverse effects. Biomed Res Int 2014. http://dx.doi.org/10.1155/2014/656370
  • Lameh J, McFarland K, Ohlsson J, et al. Discovery of potential antipsychotic agents possessing pro-cognitive properties. Naunyn Schmiedebergs Arch Pharmacol 2012;385:313–23
  • Hirose T, Kikuchi T. Aripiprazole, a novel antipsychotic agent: dopamine D2 receptor partial antagonist. J Med Invest 2005;52:284–90
  • Butini S, Gemme S, Campiani G, et al. Discovery of a new class of potential multifunctional atypical antipsychotic agents targeting dopamine D3 and serotonin 5-HT1A and 5-HT2A receptors: design, synthesis, and effects on behavior. J Med Chem 2009;52:151–69
  • Zajdel P, Marciniec K, Maślankiewicz A, et al. Quinoline-and isoquinoline-sulfonamide derivatives of LCAP as potent CNS multi-receptor-5-HT1A/5-HT2A/5-HT7 and D2/D3/D4-agents: the synthesis and pharmacological evaluation. Bioorg Med Chem 2012;20:1545–56
  • Zajdel P, Marciniec K, Maślankiewicz A, et al. Antidepressant and antipsychotic activity of new quinoline- and isoquinoline-sulfonamide analogs of aripiprazole targeting serotonin 5-HT1A/5-HT2A/5-HT7 and dopamine D2/D3 receptors. Eur J Med Chem 2013;60:42–50
  • Marazziti D, Baroni S, Bosini F, et al. Serotonin receptors of type 6 (5-HT6): from neuroscience to clinical pharmacology. Curr Med Chem 2013;20:371–7
  • Glennon RA, Siripurapu U, Roth BL, et al. The medicinal chemistry of 5-HT6 receptor ligands with a focus on arylsulfonyltryptamine analogs. Curr Top Med Chem 2010;10:579–95
  • Kołaczkowski M, Marcinkowska M, Bucki A, et al. Nowel arylsulfonamide derivatives with 5-HT6/5-HT7 receptor antagonism targeting behavioral and psychological symptoms of dementia. J Med Chem 2014;57:4543–57
  • Pawłowski M, Chłoń G, Obniska J, et al. Synthesis, 5-HT1A and 5-HT2A receptor affinity of new 1-phenylpiperazinylpropyl derivatives of purine-2,6-and pyrrolidine-2,5-diones. Il Farmaco 2000;55:461–8
  • Chłoń G, Pawłowski M, Duszyńska B, et al. Synthesis, 5-HT1A and 5-HT2A receptor activity of new 1-phenylpiperazinylpropyl derivatives with arylalkyl substituents in position 7 of purine-2,6-dione. Pol J Pharmacol 2001;53:359–68
  • Zajdel P, Bojarski AJ, Byrtus H, et al. Preliminary study on application of impregnated synthetic peptide TLC stationary phases for the pre-screening of 5-HT1A ligands. Biomed Chromatogr 2003;17:312–7
  • Chłoń-Rzepa G, Żmudzki P, Zajdel P, et al. 7Arylpiperazinylalkyl and 7-tetrahydroisoquinolinylalkyl derivatives of 8-alkoxy-purine-2,6-dione and some of their purine-2,6,8-trione analogs as 5-HT1A, 5-HT2A, and 5-HT7 serotonin receptor ligands. Bioorg Med Chem 2007;15:5239–50
  • Jastrzębska-Więsek M, Partyka A, Chłoń-Rzepa G, et al. Potential anxiolytic, but not antidepressant activity of new 7-arylpiperazinylbutyl-8-morpholinyl-purine-2,6-dione analogs in mice. Acta Biol Cracov Ser Zool 2011;53:31–7
  • Chłoń-Rzepa G, Żmudzki P, Satała G, et al. New 8-aminoalkyl derivatives of purine-2,6-dione with arylalkyl, allyl or propynyl substituents in position 7, their 5-HT1A, 5-HT2A, and 5-HT7 receptor affinity and pharmacological evaluation. Pharmacol Rep 2013;65:15–29
  • Chłoń-Rzepa G, Żmudzki P, Pawłowski M, et al. New 7-arylpiperazinylalkyl-8-morpholin-4-yl-purine-2,6-dione derivatives with anxiolytic activity – synthesis, crystal structure and structure–activity study. J Mol Struct 2014;1067:243–51
  • Partyka A, Chłoń-Rzepa G, Wasik A, et al. Antidepressant-and anxiolytic-like activity of 7-phenylpiperazinylalkyl-1,3-dimethyl-purine-2,6-dione derivatives with diversified 5-HT1A receptor functional profile. Bioorg Med Chem 2015;23:212–21
  • Chłoń-Rzepa G, Zagórska A, Bucki A, et al. New arylpiperazinylalkyl derivatives of 8-alkoxy-purine-2,6-dione and dihydro[1,3]oxazolo[2,3-f]purinedione targeting the serotonin 5-HT1A/5-HT2A/5-HT7 and dopamine D2 receptors. Arch Pharm (Weinheim) 2015;348:242–53
  • Zygmunt M, Sapa J, Chłoń-Rzepa G, et al. 7-3-Chlorophenypiperazinylalkyl derivatives of 8-alkoxy-purine-2,6-dione as a serotonin receptor ligands with potential antidepressant activity. Pharmacol Rep 2014;66:505–10
  • Eckstein M, Gorczyca M, Zejc A. About the oxidative bromination of methylxanthines. Acta Pharm Yugoslav 1972;22:133–6
  • Gorczyca M, Mogilnicka E, Wantuch C. Synthesis of 1-and 7-β-hydroxypropyl-8-cycloalkylamino-dimethylxanthines. Dissert Pharm Pharmacol 1970;22:403–7
  • Seela F, Ramzaeva N, Rosemeyer H. Purines. Sci Synth 2003;16:945–1108
  • Klingler KH. 8-Substituted xanthine derivatives. Ger. Offen, DE 2253075 A1 19730524, 1973
  • Klinger KH. Synthesis of bronchospasmolytically effective beta-phenylethylaminoalkyl xanthines. Arzneimittelforschung 1977;27:4–14
  • Agilent. CrysAlis PRO. Yarnton, England: Agilent Technologies UK Ltd; 2011
  • Sheldrick GM. A short history of SHELX. Acta Crystallogr., A, Found. Crystallogr 2008;64:112–22
  • Farrugia LJ. WinGX suite for small-molecule single-crystal crystallography. J Appl Cryst 1999;32:837–8
  • Farrugia LJ. WinGX and ORTEP for Windows: an update. J Appl Cryst 2012;45:849–54
  • Bojarski AJ, Cegła MT, Charakchieva-Minol S, et al. Structure-activity relationship studies of CNS agents. Part 9: 5-HT1A and 5-HT2 receptor affinity of some 2-and 3-substituted 1,2,3,4-tetrahydro-beta-carbolines. Pharmazie 1993;48:289–94
  • Paluchowska MH, Bugno R, Duszyńska B, et al. The influence of modifications in imide fragment structure on 5-HT1Aand 5-HT7 receptor affinity and in vivo pharmacological properties of some new 1-(m-trifluoromethylphenyl)piperazines. Bioorg Med Chem 2007;15:7116–25
  • Cheng Y, Prusoff WH. Relationship between the inhibition constant (KI) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol 1973;22:3099–108
  • Czopek A, Kołaczkowski M, Bucki A, et al. Novel spirohydantoin derivative as a potent multireceptor-active antipsychotic and antidepressant agent. Bioorg Med Chem 2015;23:3436–47
  • Kowalski P, Jaśkowska J, Bojarski AJ, et al. Evaluation of 1-arylpiperazine derivative of hydroxybenzamides as 5-HT 1A and 5-HT7 serotonin receptor ligands: an experimental and molecular modeling approach. J Heterocyclic Chem 2011;48:192–8
  • Kołaczkowski M, Bucki A, Feder M, Pawłowski M. Ligand-optimized homology models of D1 and D2 dopamine receptors: application for virtual screening. J Chem Inf Model 2013;53:638–48
  • Chien EYT, Liu W, Zhao Q, et al. Structure of the human dopamine D3 receptor in complex with a D2/D3 selective antagonist. Science 2010;330:1091–5
  • Cherezov V, Rosenbaum DM, Hanson MA, et al. High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. Science 2007;318:1258–65
  • Jain E, Bairoch A, Duvaud S, et al. Infrastructure for the life sciences: design and implementation of the UniProt Website. BMC Bioinf 2009;10:136
  • Kurowski MA, Bujnicki JM. GeneSilico protein structure prediction meta-server. Nucleic Acids Res 2003;31:3305–7
  • Arnold K, Bordoli L, Kopp J, Schwede T. The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling. Bioinforma Oxf Engl 2006;22:195–201
  • Sastry GM, Adzhigirey M, Day T, et al. Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments. J Comput Aided Mol Des 2013;27:221–34
  • Sherman W, Beard HS, Farid R. Use of an induced fit receptor structure in virtual screening. Chem Biol Drug Des 2006;67:83–4
  • Sherman W, Day T, Jacobson MP, et al. Novel procedure for modeling ligand/receptor induced fit effects. J Med Chem 2006;49:534–53
  • Paluchowska MH, Bojarski AJ, Charakchieva-Minol S, Wesołowska A. Active conformation of some arylpiperazine postsynaptic 5-HT(1A) receptor antagonists. Eur J Med Chem 2002;37:273–83
  • Lopez-Rodriguez ML, Morcillo MJ, Rovat TK, et al. Synthesis and structure-activity relationships of a new model of arylpiperazines. 4. 1-[omega-(4-Arylpiperazin-1-yl)alkyl]-3-(diphenylmethylene)-2, 5-pyrrolidinediones and-3-(9H-fluoren-9-ylidene)-2, 5-pyrrolidinediones: study of the steric requirements of the terminal amide fragment on 5-HT1A affinity/selectivity. J Med Chem 1999;42:36–49
  • Bojarski AJ, Duszyńska B, Kołaczkowski M, et al. The impact of spacer structure on 5-HT7 and 5-HT1A receptor affinity in the group of long-chain arylpiperazine ligands. Bioorg Med Chem Lett 2004;14:5863–6
  • Lewgowd W, Bojarski AJ, Szczesio M, et al. Synthesis and structural investigation of some pyrimido[5,4-c]quinolin-4(3H)-one derivatives with a long-chain arylpiperazine moiety as potent 5-HT(1A/2A) and 5-HT(7) receptor ligands. Eur J Med Chem 2011;46:3348–61
  • Shapiro DA, Renock S, Arrington E, et al. Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacology. Neuropsychopharmacology 2003;28:1400–11
  • Kleven MS, Barret-Glévoz C, Bruins Slot L, Newman-Tancredi A. Novel antipsychotic agents with 5-HT(1A) agonist properties: role of 5-HT(1A) receptor activation in attenuation of catalepsy induction in rats. Neuropharmacology 2005;49:135–43
  • Schmidt CJ, Sorensen SM, Kenne JH, et al. The role of 5-HT2A receptors in antipsychotic activity. Life Sci 1995;56:2209–22
  • Herbert Y, Meltzer MD. The role of serotonin in antipsychotic drug action. Neuropsychopharmacology 1999;21:106S–15
  • Burda K, Czubak A, Kus K, et al. Influence of aripiprazole on the antidepressant, anxiolytic and cognitive functions of rats. Pharmacol Rep 2011;63:898–907
  • Blier P, Blondeau C. Neurobiological bases and clinical aspects of the use of aripiprazole in treatment-resistant major depressive disorder. J Affect Disord 2011;128:S3–10
  • Norquist RE, Risterucci C, Moreau JL, et al. Effects of aripiprazole/OPC-14597 on motor activity, pharmacological models of psychosis, and brain activity in rats. Neuropharmacology 2008;54:405–16
  • Morozowa MA, Lepilkina TA, Rupchev GE, et al. Add-on clinical effects of selective antagonist of 5HT6 receptors AVN-211 (CD-008-0173) in patients with schizophrenia stabilized on antipsychotic treatment: pilot study. CNS Spectr 2014;19:316–23
  • Goff DC, Hill M, Barch D. The treatment of cognitive impairment in schizophrenia. Pharmacol Biochem Behav 2011;99:245–53
  • Tadori Y, Miwa T, Tottori K, et al. Aripiprazole's low intrinsic activities at human dopamine D2L and D2S receptors render it a unique antipsychotic. Eur J Pharmacol 2005;515:10–19
  • Zagórska A, Kołaczkowski M, Bucki A, et al. Structure-activity relationships and molecular studies of novel arylpiperazinylalkyl purine-2,4-diones and purine-2,4,8-triones with antidepressant and anxiolytic-like activity. Eur J Med Chem 2015;97:142–54
  • Wang Q, Mach RH, Luedtke RR, Reichert DE. Subtype selectivity of dopamine receptor ligands: insights from structure and ligand-based methods. J Chem Inf Model 2010;50:1970–85
  • Shonberg J, Herenbrink CK, López L, et al. A structure–activity analysis of biased agonism at the dopamine D2 receptor. J Med Chem 2013;56:9199–221
  • Kołaczkowski M, Marcinkowska M, Bucki A, et al. Novel 5-HT6 receptor antagonists/D2 receptor partial agonists targeting behavioral and psychological symptoms of dementia. Eur J Med Chem 2015;92:221–35
  • Urban JD, Vargas GA, von Zastrow M, Mailman RB. Aripiprazole has functionally selective actions at dopamine D2 receptor-mediated signalling pathways. Neuropsychopharmacology 2007;32:67–77
  • Costall B, Domeney AM, Naylor RJ. Locomotor hyperactivity caused by dopamine infusion into the nucleus accumbens of rat brain: specificity of action. Psychopharmacology 1984;82:174–80
  • Cools AR. Mesolimbic dopamine and its control of locomotor activity in rats: differences in pharmacology and light/dark periodicity between the olfactory tubercle and the nucleus accumbens. Psychopharmacology 1986;88:451–9
  • Ellenbroek BA. Treatment of schizophrenia: a clinical and preclinical evaluation of neuroleptic drugs. Pharmacol Ther 1993;57:1–78

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