Microwave-Assisted Synthesis of 1,3-Benzothiazol-2(3H)-one Derivatives and Analysis of Their Antinociceptive Activity

Abstract

A rapid and efficient method was developed for synthesis of 6-acyl-1,3-benzothiazol-2(3H)-one derivatives under microwave irradiation (MWI) conditions. The reaction times were shortened compared to conventional heating. Additionally, we synthesized acetic acid and acetamide derivatives of 1,3-benzothiazol-2(3H)-one, 6-acyl-1,3-benzothiazol-2(3H)-one, 5-chloro-1,3-benzothiazol-2(3H)-one and 6-acyl-5-chloro-1,3-benzothiazol-2(3H)-one with the microwave-assisted method and analyzed their antinociceptive activity with the tail flick, tail clip, hot plate and writhing tests. Among the synthesized compounds, 3-[2-(4-ethylpiperazin-1-yl)-2-oxoethyl]-1,3-benzothiazol-2(3H)-one (6a), 5-chloro-3-{2-oxo-2-[4-(propan-2-yl) piperazin-1-yl]ethyl}-1,3-benzothiazol-2(3H)-one (7e) and 3-[2-(4-butylpiperazin-1-yl)-2-oxoethyl]-5-chloro-1,3-benzothiazol-2(3H)-one (8e) showed significant antinociceptive activity in the tail clip, tail flick, hot plate and writhing tests.

Supporting Information available online at http://www.thieme-connect.de/ejournals/toc/amf

Key words

1,3-benzothiazol-2(3H)-one - tail flick test - tail clip test - hot plate test - writhing test - microwave-assisted synthesis

• References

• 1 Praveen Rao PN, Knaus EE. Evolution of nonsteroidal anti-inflammatory drugs (NSAIDs): cyclooxygenase (COX) inhibition and beyond. J Pharm Pharm Sci 2008; 11 (02) 81-110
• 2 Patrono C, Rocca B. Nonsteroidal antiinflammatory drugs: Past, present and future. Pharmacol Res 2009; 59 (05) 285-289
• 3 Graham DY, Chan FKL. NSAIDs, risks, and gastroprotective strategies: Current status and future. Gastroenterology 2008; 134 (04) 1240-1246
• 4 Koeberle A, Werz O. Inhibitors of the microsomal prostaglandin E2 synthase-1 as alternative to non steroidal anti-inflammatory drugs (NSAIDs) – a critical review. Curr Med Chem 2009; 16 (32) 4274-4296
• 5 Fujiyoshi T, Dozen M, Ikeda K et al. Involvement of prostaglandins in kaolin-induced writhing reaction in mice. J Pharmacobiodyn 1989; 12 (08) 476-482
• 6 Takano S. Inhibition of phospholipase A2 by tiaramide in rabbit platelets. Jpn J Pharmacol 1985; 39 (03) 307-316
• 7 Inomata N, Osuna H, Yamaguchi J et al. Safety of selective cyclooxygenase-2 inhibitors and a basic non-steroidal anti-inflammatory drug (NSAID) in Japanese patients with NSAID-induced urticaria and/or angioedema: comparison of meloxicam, etodolac and tiaramide. J Dermatol 2007; 34 (03) 172-177
• 8 Önkol T, Doğruer DS, Ito S et al. Synthesis and antinociceptive activity of (5-chloro-2-benzothiazolinon-3-yl)acetamide derivatives. Arch Pharm 2000; 333 (10) 337-340
• 9 Ferreira SH, Lorenzetti BB, Devissaguet M et al. S14080, a peripheral analgesic acting by release of an endogenous circulating opioid-like substance. Br J Pharmacol 1995; 114 (02) 303-308
• 10 Poupaert J, Carato P, Colacino E. 2(3H)-benzoxazolone and bioisosters as “privileged scaffold” in the design of pharmacological probes. Curr Med Chem 2005; 12 (07) 877-885
• 11 Ünlü S, Önkol T, Dündar Y et al. Synthesis and analgesic and anti-inflammatory activity of some new 6-acyl-2-benzoxazolinone and 6-acyl-2-benzothiazolinone derivatives with acetic acid and propanoic acid residues. Arch Pharm 2003; 336 (08) 353-360
• 12 Uzun L. Synthesis of some 6-(substitute-thiazole-4-yl)-2-oxo-3H-benzothiazol derivatives and studies of their inhibitor effects on cyclooxygenase [dissertation]. Ankara: Gazi University; 2007
• 13 Claasz M. Thionylindigo. Ber Dtsch Chem Ges 1912; 45: 1015-1032
• 14 Önkol T, Dündar Y, Sırmagül B et al. (2-Oxobenzazolin-3-yl)alkanoic acid derivatives and antinociceptive activity. J Fac Pharm Gazi 2002; 19 (01) 15-24
• 15 Adak S. Synthesis of some 5-chloro-6-(thiazole-4-yl)-2-oxo-3H-benzothiazol derivatives and studies of their inhibitor effects on cyclooxygenase [dissertation]. Ankara: Gazi University; 2007
• 16 Yous S, Poupaert JH, Lesieur I et al. AlCl3-DMF reagent in the Friedel-Crafts reaction. Application to the acylation reaction of 2(3H)-benzothiazolones. J Org Chem 1994; 59 (06) 1574-1576
• 17 Dushamov DA, Mukhamedov NS, Aliev NA et al. Benzazoles. 2. Relative activity of catalysts and 4-substituted benzoyl chlorides in the acylation of benzothiazolin-2-ones. Chem Heterocycl Comp 2002; 38 (04) 438-441
• 18 Ucar H, Van der Poorten K, Depovere P et al. “Fries like” rearrangement: a novel and efficient method for the synthesis of 6-acyl-2(3H)-benzoxazolones and 6-acyl-2(3H)-benzothiazolones. Tetrahedron 1998; 54 (09) 1763-1772
• 19 Petrov OI, Antonova ATS, Kalcheva VB et al. Synthesis of 6-benzoyl-2(3H)-benzothiazolones and compounds of their reduction and alkylation. Dokl Bolg Akad Nauk 1994; 47 (03) 31-34
• 20 Yous S, Lebegue N, Poupaert JH et al. Lipid-lowering properties of 6-benzoyl-2(3H)-benzothiazolone and structurally related compounds. J Enzyme Inhib Med Chem 2005; 20 (06) 525-532
• 21 Yous S, Poupaert JH, Chavatte P et al. Synthesis and pharmacological evaluation of analgesic 6-substituted 2(3H)-benzothiazolones. Drug Des Discov 2001; 17 (04) 331-336
• 22 Lesieur D, Lespagnol C, Yous S. Preparation of 6-acylbenzothiazolinones and analogs as drugs. Eur Patent Application EP 395526 A1 19901031; 1990
• 23 Nimmich W. Benzothiazolinone-3-yl carboxylic acids. J Prakt Chem 1965; 27 (3–4) 220-224
• 24 D’Amico JJ, Bollinger FG. Synthesis of 2-oxo-3-benzothiazolineacetyl chloride, 5-chloro-2-oxo-3-benzothiazolineacetyl chloride and derivatives. J Heterocycl Chem 1988; 25 (04) 1183-1190
• 25 Arakawa S, Ogawa S, Arakawa E et al. 2-Benzothiazolinone derivatives. Jpn Kokai Tokkyo Koho JP60228467 A 19851113 1985;
• 26 Umios S. N-Substituted and N,N-disubstituted aminocarbonylalkyl compounds. U.S. Patent Application US 3661921 A 19720509 1972;
• 27 Toshiyuki T, Yohichi K, Shigenobu K. Pharmacological investigations of benzothiazoline derivatives. ArzneimittelForschung 1972; 22 (04) 711-715
• 28 Bianchi C, Franceschini J. Experimental observations of Haffner’s method for testing analgesic drugs. Br J Pharmacol 1954; 9: 280-284
• 29 Dajani EZ, Larsen KR, Taylor J et al. 1,1-Dimethylheptyl-8-tetrahydrocannabinol-11-oic acid: A novel orally active cannabinoid with analgesic and antiinflammatory properties. J Pharmacol Exp Ther 1999; 291 (01) 31-38
• 30 D’Amour FE, Smith DL. A method for determining loss of pain sensation. J Pharmacol Exp Ther 1941; 72: 74-79
• 31 Eddy NB, Leimbach D. Synthetic analgesic (II): Diethylbutenyl and diethylbutylamines. J Pharmacol Exp Ther 1953; 107: 385-393
• 32 Noble F, Smadja C, Raques BP. Role of endogenous cholecystokinin in the facilitation of mu-mediated antinociception by delta-opioid agonists. J Pharmacol Exp Ther 1994; 271 (03) 1127-1134
• 33 Koster R, Anderson M, Beer EJ. Acetic acid for analgesic screening. Pharmacology 1958; 412: 1626
• 34 Ferrira SH, Vane JR. New aspects on the model of action of nonsteroid anti-inflammatory drugs. Annu Rev Pharmacol 1974; 14: 57-73
• 35 Perianayagam JB, Sharma SK, Joseph A et al. Evaluation of anti-pyretic and analgesic activity of Emblica officinalis Gaertn. J Ethnopharmacol 2004; 95 (01) 83-85
• 36 Kilic FS, Erol K. Central components in the antinociceptive activity of dipyrone in mice. Inflammopharmacology 2000; 8 (03) 259-265