Screening for antidepressant, sedative and analgesic activities of novel fused thiophene derivatives

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Screening for antidepressant, sedative and analgesic activities of novel fused thiophene derivatives

This study was aimed at the synthesis of fused benzothiophene derivatives containing heterocyclic moiety. The reaction of the tetrahydrobenzo[b]thiophene derivatives 1a,b with ethoxycarbonylisothiocyanate afforded the thiourea derivatives 2a,b. Cyclization of the latter products gave the annulated benzo[b]thienopyrimidine derivatives 3a,b. Compounds 2a,b and 3a underwent a series of heterocyclization reactions through the reaction with some chemical reagents to give the new benzo[b]thienopyrimidine derivatives 5a,b to 8a-c. Also, this work was extended to study the potential role of the novel synthesized thiourea derivative 2a and benzo[b]thienopyrimidine derivatives 3a, 5b, 6a and 8b as antidepressant, sedative or analgesic agents at two doses (15 or 30 mg kg-1 body mass). Some compounds (2a, 3a and 5b) showed mild antidepressant activity in the forced-swimming test. No compound showed sedative effect. Visceral pain evoked by i.p. injection of acetic acid in mice was significantly inhibited by all compounds at a high doses.

E. Palaska, M. Aytemir, I. T. Uzbay and D. Erol, Synthesis and antidepressant activities of some 3,5-diphenyl-2-pyrazolines, Eur. J. Med. Chem., 36 (2001) 539-543; DOI: 10.1016/S0223-5234(01)01243-0.

M. F. Şahin, B. Badieogh, M. Gökçe, E. Küpeli, E. Yesilada, Synthesis and analgesic and antiinflammatory activity of methyl 6-substituted-3(2H)-pyridazinone-2-yl acetate derivatives, Arch. Pharm.337 (2004) 445-452.

A. A. Bilgin, E. Palaska, R. Sunal and B. Gumusel, 1,3,5-Triphenyl-2-pyrazolines with antidepressant activities, Pharmazie49 (1994) 67-69.

O. M. E. Abdel-Salam and S. M. Nofal and S. M. El-Shenawy, Evaluation of the anti-inflammatory and anti-nociceptive effects of different antidepressants in the rats, Pharmacol. Res.48 (2003) 157-165; DOI: 10.1016/S1043-6618(03)00106-3.

M. Vrethem, J. Boivie, H. Arnqvist, H. Holmgren, T. Lindstrom and L. H. Thorell, A comparison of amitriptyline and maprotiline in the treatment of painful polyneuropathy in diabetics and non-diabetics, Clin. J. Pain13 (1997) 313-323; DOI: 10.1079/00002508-199712000-00009.

S. S. Bahekar and D. B. Shinde, Synthesis and anti-inflammatory activity of some [4,6-(4-substiuted aryl)-2-thioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl]-acetic acid derivatives, Bioorg. Med. Chem. Lett.14 (2004) 1733-1736.

J. P. Beck, M. A. Curry, R. J. Chorvat, L. W. Fitzgerald, P. J. Gilligan, R. Zaczek and G. L. Trainor, Thiazolo[4,5-d]pyrimidine thiones and -ones as corticotropin-releasing hormone (CRH-R1) receptor antagonists, Bioorg. Med. Chem. Lett.9 (1999) 1185-1188.

V. Alagarsamy, S. Meena, K. V. Ramseshu, V. R. Solomon, K. Thirumurugan, K. Dhanabal and M. Murugan, Synthesis, analgesic, anti-inflammatory, ulcerogenic index and antibacterial activities of novel 2-methylthio-3-substituted-5,6,7,8-tetrahydrobenzo-(b)thieno[2,3-d]pyrimidin-4 (3H)-ones, Eur. J. Med. Chem.41 (2006) 1293-1300.

W. W. Wardakhan, H. M. Gaber, S. A. Ouf and S. M. Sherif, Studies on 2-aminothiophenes: synthesis, transformations and biological evaluation of functionally substituted thiophenes and their fused derivatives, Phosph. Sul. Sil.180 (2005) 601-618; DOI: 10.1080/104265090517406.

W. W. Wardakhan, H. Z. Shams and H. E. Moustafa, Synthesis of polyfunctionally substituted thiophene, thieno[2,3-b]pyridine and thieno[2,3-d]pyrimidine derivatives, Phosph. Sul. Sil.180 (2005) 1815-1827; DOI: 10.1080/104265090889422.

W. W. Wardakhan, G. A. Elmegeed, F. M. Manhi, Utility of 2-aminothiophene-3-carboxamide in the synthesis of biologically active fused heterocyclic derivatives, Phosph. Sul. Sil.180 (2005) 125-140; DOI: 10.1080/104265090889422.

W. W. Wardakhan and S. A. Ouf, Reaction of cyanoacetamide with benzoyl isothiocyanate: synthesis of pyridine, pyrido[2,2-a]-1,2,3-triazine, pyrazolo[3,4-d]-1,2,3-triazine and thiazole derivatives, Egypt. J. Chem.48 (2005) 393-406.

J. Graff, S. Harder, O. Wahl, E. H. Scheuermann and J. Gossmann, Anti-inflammatory effects of clopidogrel intake in renal transplant patients: effects on platelet-leukocyte interactions, platelet CD40 ligand expression, and proinflammatory biomarkers, Clin. Pharmacol. Ther.78 (2005) 468-476.

A. Hymete, J. Rohloff, H. Kjosen and T. H. Iversen, Acetylenic thiophenes from the roots of Escinops ellenbeckii from Ethiopia, Nat. Prod. Res.19 (2005) 755-761; DOI: 10.1080/1478641042000301711.

R. A. Tapia, L. Alegria, C. D. Pessoa, C. Salas, M. J. Cortes, J. A. Valderrama, M. E. Sarciron, F. Pautet, N. Walchshofer and H. Fillion, Synthesis and antiprotozoal activity of naphthofuranquinones and naphthothiophenequinones containing a fused thiazole ring, Bioorg. Med. Chem.11 (2003) 2175-2182; DOI: 10.1016/S0968-0896(03)00122-6.

P. Dallemagne, L. P. Khanh, A. Alsaidi, I. Varlet, V. Collot, M. Paillet, R. Bureau and S. Rault, Synthesis and biological evaluation of five-membered heterocycles fused to cyclopenta[c]thiophene as new antitumer agents, Bioorg. Chem.11 (2003) 1161-1167; DOI: 10.1016/S0968-0896(02)00654-5.

M. E. Migaud, R. C. Wilmouth, G. I. Mills, G. J. Wayne, C. Risley, C. Chambers, S. J. F. Macdonald and C. J. Schofield, 5,5-Fused thiophene gamma-lactams as templates for serine protease inhibition, Chem. Com.12 (2002) 1274-1275.

M. Pietsch and M. Gutschow, Alternate substrate inhibition of cholesterol esterase by thieno [2,3-d][1,3]oxazin-4-ones, J. Biol. Chem.277 (2002) 24006-24013.

R. M. Mohareb and F. M. Manhi, Reaction of 2-diazo-4,5,6,7-tetrahydro-benzo[b]thiophene-3-carboxylate with 3-iminobutyronitrile: synthesis of thiophene and their fused derivatives, Heteroatom. Chem.11 (2000) 403-412; DOI: 10.1002/1098-1071(2000).

W. W. Wardakhan, N. A. Louca and M. M. Kamel, The reaction of 2-aminocyclohexeno-[b]thiophene derivatives with ethoxycarbonylisothiocyanate: synthesis of fused thiophene derivatives with antimicrobial and antifungal activities, Acta Chim.54 (2007) 229-241.

R. D. Porsolt, M. Le Pichon and M. Jalfre, Depression: a new animal model sensitive to antidepressant treatments, Nature266 (1977) 730-732; DOI: 10.1038/266730a0.

R. Koster, M. Anderson and E. J. De Beer, Acetic acid for analgesic screening, Fed. Proc.18 (1959) 412-413.

S. Reyes and K. Burgess, On formation of thiohydantoins from amino acids under acylation conditions, J. Org. Chem.71 (2006) 2507-2509; DOI: 10.102/jo052576.

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