Abstract
The present research paper reports the synthesis and biological evaluation of 6-(3-substitutedpropoxyl)benzo[d][1,3]oxathiol-2-ones as potential atypical antipsychotic agents. Accordingly, 10 derivatives with either amino or aryloxy substituents were synthesized. Potential antipsychotic activity of these compounds in terms of D2 antagonism was evaluated by their ability to inhibit apomorphine-induced climbing behavior in mice and 5-HT2 antagonistic activity of synthesized compounds was assessed by studying inhibition of 5-HTP-induced head twitches. Non-specific D2 blockade was evaluated by studying propensity of these compounds to produce catalepsy in mice. All the synthesized compounds were found to exhibit D2 and 5-HT2 antagonist activity in behavioral models. However, they also induced mild to severe catalepsy. Among the 10 compounds tested, 5b and 5e exhibited maximum ‘atypical antipsychotic activity like’ profile.
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References
Aaron C, David M (2004) J Young Investig. http://www.jyi.org/volumes/volume11/issue3/articles/clarke.html
Aparna MVL, Sati N, Veer VS, Bhosale SH, Bhosale MS, Bodhankar SL, Mahadik KR, Kadam SS (2005) Synthesis and 5-HT2A antagonistic activity of some 7-[3-(substituted amino) propoxyll]-4-methyl chromen-2ones. Ind J Pharm Sci 67:467–472
Bhosale SH, Rode MS, Basagare SS, Gawai AA, Bhosale MS, Mahadik KR, Kadam SS (2006) Synthesis and antipsychotic activity of new coumarinoacetamides. Ind J Hetero Chem 15:267–270
Evans K, McGrath J, Milns R (2003) Searching for schizophrenia in ancient Greek and Roman literature: a systematic review. Acta Psychiatr Scand 107:323–330
Kesten SR, Heffner TG, Johnson SJ, Pugsley TA, Wright JL, Wise GLD (1999) Design, synthesis, and evaluation of chromen-2-ones as potent and selective human dopamine D4 antagonists. J Med Chem 42:3718–3725
Khisti RT, Mandhane SN, Chopde CT (1998) The neurosteroid 3α-hydroxy-5α-pregnan-20-one induces catalepsy in mice. Neurosci Lett 251:85–88
Kim SH, Rhee GS, Oh S, Park WK (1999) NMDA receptor antagonists inhibit apomorphine-induced climbing behavior not only in intact mice but also in reserpine-treated mice. Behav Brain Res 100:135–142
Lieberman JA, Johns CA, Kane JM, Rai K, Pisciotta AV, Saltz BL, Howard A (1988) Clozapine- induced agranulocytosis: non-cross-reactivity with other psychotropic drugs. J Clin Psychiatry 49:271–277
Lowe JA, Seeger TF, Nagel AA, Howard HR, Seymour PA, Heym JH, Ewing FE, Newman ME, Schmidt AW, Furman JS, Vincent LA, Maloney PR, Robinson GL, Reynolds LS, Vinick FJ (1991) 1-Naphthylpiperazine derivatives as potential atypical antipsychotic agents. J Med Chem 34:1860–1866
Martin AR (1997) Burger’s Medicinal Chemistry and drug discovery. Wiley-Interscience, New York
Masaguer CF, Ravina E, Fontenla JA, Brea J, Tristan H, Loza MI (2000) Butyrophenone analogues in the cabazole series as potential atypical antipsychotic: synthesis and determination of a affinities at D2, 5-HT2A, 5-HT2B, and 5-HT2C receptors. Eur J Med Chem 35:83–95
Meltzer HY, Matsubara S, Lee JC (1989) Illuminating the molecular basis for some antipsychotic drug-induced metabolic burden. J Pharmacol Exp Ther 251:238–246
Navas F, Tang FLM, Schaller LT, Norman MH (1998) Analogues of the potential antipsychotic agent 1192u90: amide modification. Bioorg Med Chem 6:811–823
Ravin AE, Masaguer CF (2001) Conformationally constrained butyrophenones. Synthesis and evaluation as antipsychotics. Curr Med Chem Cent Nerv Syst Agents 1:43–62
Ross BS, Ramsey LA (2002) Innovation in pharmacy practice: disease management. Drug Topics. May:81–90
Shelke SM, Sushilkumar SatiN, Veer VS, Bhosale SH, Bhodhankar SL, Mahadik KR, Kadam SS (2005) 7-[(4-Substituted phenyl-piperazine-1-yl)-alkoxy]-4-methylchomene-2-ones as potential atypical antipsychotics: synthesis and pharmacological evaluation. Ind J Chem 44B:2295–2300
Taverne T, Diouf O, Depreux P, Poupaert JH, Lesieur D, Guardiola-Lemaître B, Renard P, Rettori M-C, Caignard D-H, Pfeiffer B (1998) Novel benzothiazoline-2one and benzoxazin-3-one arylpiperazine derivatives with mixed 5HT1A/D2 affinity as potential atypical antipsychotics. J Med Chem 41:2010–2018
Werner G (1943) US Patent No 2332418
Wirshing DA, Wirshing WC, Kysar L, Berisford MA, Goldstein D, Pashdag J, Mintz J, Marder SR (1999) Novel antipsychotics: comparison of weight gain liabilities. J Clin Psychiatry 60:358–363
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Dash, R.C., Suryawanshi, M.R., Shelke, S.M. et al. Benzo[d][1,3] oxathiols: synthesis and biological evaluation as potential atypical antipsychotic agents. Med Chem Res 20, 29–35 (2011). https://doi.org/10.1007/s00044-009-9278-5
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DOI: https://doi.org/10.1007/s00044-009-9278-5