Synthesis and antiinflammatory activity of novel 2,5-disubstituted thiophene derivatives
New series of 2,5-disubstituted thiophenes were synthesized. Thiosemicarbazones 1a-b were reacted with various reagents, such as diethyl-2-bromomalonate, ethyl-2-chloroacetoacetate, thioglycolic acid, 4-substituted phenacyl bromides, and acetic anhydride, to afford heterocyclic substituted thiophene derivatives 2a-b, 3a-b, 4a-b, 5a-b, 6a-b, and 7a-b, respectively. Moreover, cyclization of the key intermediate 1b with chloroacetic acid yielded thiazolidine 9, which on reaction with appropriate aromatic aldehydes afforded the corresponding arylidene derivatives 10a-f. Finally, reaction of N\-arylidene cyanoacetohydrazide 11 with sulfur and phenylisothiocyanate yielded thiazoline derivative 12, which on treatment with triethylorthoformate and acetic anhydride afforded thiazolo[4,5-d]pyrimidinone derivative 13. Some of the newly synthesized compounds showed promising antiinflammatory activity.
Synthesis and antiinflammatory activity of novel 2,5-disubstituted thiophene derivatives
New series of 2,5-disubstituted thiophenes were synthesized. Thiosemicarbazones 1a-b were reacted with various reagents, such as diethyl-2-bromomalonate, ethyl-2-chloroacetoacetate, thioglycolic acid, 4-substituted phenacyl bromides, and acetic anhydride, to afford heterocyclic substituted thiophene derivatives 2a-b, 3a-b, 4a-b, 5a-b, 6a-b, and 7a-b, respectively. Moreover, cyclization of the key intermediate 1b with chloroacetic acid yielded thiazolidine 9, which on reaction with appropriate aromatic aldehydes afforded the corresponding arylidene derivatives 10a-f. Finally, reaction of N\-arylidene cyanoacetohydrazide 11 with sulfur and phenylisothiocyanate yielded thiazoline derivative 12, which on treatment with triethylorthoformate and acetic anhydride afforded thiazolo[4,5-d]pyrimidinone derivative 13. Some of the newly synthesized compounds showed promising antiinflammatory activity.
___
- Moore, P. F.; Larson, D. L.; Otterness, I. G.; Weissman, A.; Kadin, S. B.; Sweeney, F. J.; Eskra, J. D.; Nagahisa, A.; Sakakibara, M.; Carty, T. J. Inflamm. Res. 1996, 45, 54-61.
- Gans, K. R.; Galbraith, W.; Roman, R. J.; Haber, S. B.; Kerr, J. S.; Schmidt, W. K.; Smith, C.; Hewes, W. E.; Ackerman, N. R. J. Pharmacol. Exp. Ther. 1990, 254, 180-187.
- Noguchi, T.; Hasegawa, M.; Tomisawa, K.; Mitsukuchi, M. Bioorg. Med. Chem. 2003, 11, 4729-4742.
- Panagoulis, D.; Pontiki, E.; Skeva, E.; Raptopoulou, C.; Girousi, S.; Litina, D. H.; Samara, C. D. Journal of Inorganic Biochemistry 2007, 101, 623-634.
- Shen, T. Y. In A Textbook of Drug Design and Development, 5th ed.; Krogsgaard-Larsen, P.; Bundgaard, H., Eds.;;arwood Academic Publishers, 1995.
- Gauthier, J. Y.; Leblanc, Y.; Black, W. C.; Chan, C. C.; Cromlish, W. A.; Gordon, R.; Kennedey, B. P.; Lau, C. K.; Leger, S.; Wang, Z.; Ethier, D.; Guay, J.; Mancini, J.; Riendeau, D.; Tagari, P.; Vickers, P.; Wong, E.; Xu, L.; Prasit, P. Bioorg. Med. Chem. Lett. 1996, 6, 87-92.
- Woods, K. W.; McCroskey, R. W.; Michaelides, M. R.; Wada, C. K.; Hulkower, K. I.; Bell, R. L. Bioorg. Med. Chem. Lett. 2001, 11, 1325-1328.
- Holla, B. S.; Malini, K. V.; Rao, B. S.; Sarojini, B. K.; Kumari, N. S. Eur. J. Med. Chem. 2003, 38, 313-318.
- Kalkhambkar, R. G.; Kulkarni, G. M.; Shivkumar, H.; Rao, R. N. Eur. J. Med. Chem. 2007, 42, 1272-1276.
- Ali, A. M.; Saber, G. E.; Mahfouz, N. M.; El-Gendy, M. A.; Radwan, A. A.; El- Hamid, M. A. Arch. Pharm. Res. , 30, 1186-1204.
- Gurupadayya, B. M.; Gopal, M.; Padmashali, B.; Manohara, Y. N. Indian J. Pharm. Sci. 2008, 70, 572-577.
- Schenone, S.; Brullo, C.; Bruno, O.; Bondavalli, F.; Ranise, A.; Filippelli, W.; Rinaldi, B.; Capuano, A.; Falcone, G. Bioorg. Med. Chem. 2006, 14, 1698-1705.
- Schenone, S.; Bruno, O.; Ranise, A.; Bondavalli, F.; Filippelli, W.; Falcone, G.; Giordano, L.; Vitelli, M. R. Bioorg. Med. Chem. 2001, 9, 2149-2153.
- Palaska, E.; Sahin, G.; Kelicen, P.; Durlu, N. T.; Altinok, G. Il Farmaco 2002, 57, 101-107.
- Sondhi, S. M.; Dinodia, M.; Kumar, A. Bioorg. Med. Chem. 2006, 14, 4657-4663.
- Lima, P. C.; Lima, L. M.; Silva, K. C. M.; Leda, P. H. O.; Miranda, A. L. P.; Fraga, C. A. M.; Barreiro, E. J. Eur. J. Med. Chem. 2000, 35, 187-203.
- Foroumadi, A.; Mansouri, S.; Kiani, Z.; Rahmani, A. Eur. J. Med. Chem. 2003, 38, 851-854.
- Mamolo, M. G.; Vio, L. Il Farmaco 1996, 51, 71-74.
- Moreno-Manas, M.; Pleixats, R.; Andreu, R.; Garin, J.; Orduna, J.; Villacampa, B.; Levillain, E.; Salle, M. J. Mater. Chem. 2001, 11, 374-380.
- Winter, C. A.; Risley, E. A.; Nuss, G. W. Proc. Soc. Exp. Biol. Med. 1962, 111, 544-547.