Browse > Article
http://dx.doi.org/10.5012/bkcs.2007.28.5.751

Synthesis and Characterization of Novel Hydantoins as Potential COX-2 Inhibitors: 1,5-Diarylhydantoins  

Park, Hae-Sun (College of Pharmacy, Duksung Women's University)
Choi, Hee-Jeon (College of Pharmacy, Duksung Women's University)
Shin, Hea-Soon (College of Pharmacy, Duksung Women's University)
Lee, Sang-Kook (College of Pharmacy, Ewha Womans University)
Park, Myung-Sook (College of Pharmacy, Duksung Women's University)
Publication Information
Bulletin of the Korean Chemical Society / v.28, no.5, 2007 , pp. 751-757 More about this Journal
Abstract
To develop new COX-2 inhibitors, 1,5-diarylhydantoins and 1,5-diaryl-2-thiohydantoins were synthesized from phenylacetic acids by esterification, bromination, C-N bond formation and cyclization. Esters 1-3 were efficiently synthesized from the starting materials by reflux in absolute methanol for 3 h containing concentrated sulfuric acid as catalyst. Bromination was carried out with N-bromosuccinimide at rt in dichloromethane. Bromides 4-6 were reacted with aniline, p-anisidine, sulfanilamide in ethanol (or N,N-dimethylformamide) to provide the amines 7-15. Hydantoins and 2-thiohydantoins 16-46 were synthesized from amines 7-15 by treating them with potassium isocyanate (or potassium thiocyanate) and triethylamine. The synthetic process from alkyl α-anilinophenylacetate 7-15 to 3-alkylhydantoins was carried out in a one-pot reaction using alkyl isocyanate (alkyl isothiocyanate).
Keywords
Diarylhydantoins; Diaryl-2-thiohydantoins; Hydantoins; Synthesis; COX-2 inhibitors;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
Times Cited By Web Of Science : 5  (Related Records In Web of Science)
Times Cited By SCOPUS : 5
연도 인용수 순위
1 Vane, J.; Botting, J.; Botting, R. Improved Non-steroid Anti-inflammatory Drugs COX-2 Enzyme Inhibitors; Kluwer Academic Publishers and William Harvey Press: London, 1996
2 Hla, T.; Neilson, K. Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 7384   DOI   ScienceOn
3 Xie, W.; Chipman, J. G.; Robertson, D. L.; Erikson, R. L.; Simmons, D. L. Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 2692   DOI   ScienceOn
4 Talley, J. J.; Brown, D. L.; Carter, J. S.; Graneto, M. J.; Koboldt, C. M.; Masferrer, J. L.; Perkins, W. E.; Rogers, R. S.; Shaffer, A. F.; Zhang, Y. Y.; Zweifel, B. S.; Seibert, K. J. Med. Chem. 2000, 43, 775   DOI   ScienceOn
5 Kwon, S. K.; Jung, H. W.; Park, M. S. Korean J. Med. Chem. 1995, 5, 166
6 Wolfe, M. M.; Lichtenstein, D. R.; Singh, G. N. Engl. J. Med. 1999, 340, 1888   DOI   ScienceOn
7 Hwang, K. J.; Lee, S. J.; Kim, B. T.; Raucher, S. Bull. Korean Chem. Soc. 2006, 27(6), 933   DOI   ScienceOn
8 Park, M. S.; Park, H. S. Yakhak Hoeji 2003, 47, 276
9 Kirk-Othmer Encyclopedia of Chemical Technology, 2nd ed.; Interscience: New York-London-Sydney, 1966; Vol 11, pp 141- 161
10 Ware, E. Chem. Rev. 1950, 411
11 Li, J. P. Org. Chem. 1975, 40, 3414   DOI
12 Kirk-Othmer Encyclopedia of Chemical Technology, 3nd ed.; Interscience: New York-London Sydney, 1979; Vol 12, pp 692-708
13 Futaki, N.; Yoshikawa, K.; Hamasaka, Y.; Arai, I.; Higuchi, S.; Iizuka, H.; Otomo, S. Gen. Pharmacol. 1993, 24, 105   DOI   ScienceOn
14 Hardman, J. G.; Limbird, L. E. In Goodman and Gilman's The Pharmacological Basis of Therapeutics, 10th ed.; McGraw-Hill: New York, 2001; pp 688-731
15 Lombardino, G. Nonsteroidal Antiinflammtory Drugs; John Wiely & Sons: New York, 1985. 2. Allison, M. C.; Howatson, A. G.; Torrance, C. J.; Lee, F. D.; Russell, R. I. G. N. Engl. J. Med. 1992, 327, 749   DOI   ScienceOn
16 Fu, J. Y.; Masfferrer, J. L.; Seibert, K.; Raz, A.; Needleman, P. J. Biol. Chem. 1990, 265, 16737
17 Mukherjee, D.; Nissen, S. E.; Topol, E. J. JAMA 2001, 286, 954   DOI   ScienceOn
18 Gaetano, G.; Donati, M. B.; Cerletti, C. Trends Pharm. Sci. 2003, 24, 245   DOI   ScienceOn
19 Kujubu, D. A.; Fletcher, B. S.; Varnum, B. C.; Lim, R. W.; Herschman, H. R. J. Biol. Chem. 1991, 266, 12866
20 Masferrer, J. L.; Seibert, K.; Zweifel, B.; Needleman, P. Proc. Natl. Acad. Sci. U.S.A. 1992, 89, 3917   DOI   ScienceOn
21 Futaki, N.; Takahashi, S.; Yokoyama, M.; Arai, I.; Higuchi, S.; Otomo, S. Prostaglandins 1994, 47, 55   DOI   ScienceOn
22 Gans, K. R.; Galnraith, W.; Romans, 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
23 Penning, T. D.; Tally, J. J.; Bertenshaw, S. R.; Carter, J. S.; Collins, P. W.; Doctor, S.; Graneto, M. J.; Lee, L. F.; Veenhuizen, A. W.; Zhang, Y. Y.; Isakson, P. C. J. Med. Chem. 1997, 40, 1347   DOI   ScienceOn
24 Prasit, P.; Wang, Z.; Brideau, C.; Chan, C.-C.; Charleson, S.; Cromlish, W.; Ethier, D.; Evans, J. F.; Ford-Hutchinson, A. W.; Gauthier, J. Y.; Gordon, R.; Forrest, M.; Visco, D.; Patrick, D. Bioorg. Med. Chem. Lett. 1999, 9, 1773