Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Synthesis and SAR Studies for the Inhibition of TNF-$\alpha$ Production. Part 2. 2-[3-(Cyclopenthloxy)4-Methoxyphenyl]-Substituted-1-Isoindolinone Derivatives

  • Park, Joon-Seok (Institute of Bioscience ＆ Biotechnology Daewoong Pharm. Co., Ltd.) ;
  • Moon, Seong-Cheol (Institute of Bioscience ＆ Biotechnology Daewoong Pharm. Co., Ltd.) ;
  • Baik, Kyung-Up (Institute of Bioscience ＆ Biotechnology Daewoong Pharm. Co., Ltd.) ;
  • Cho, Jae-Youl (Institute of Bioscience ＆ Biotechnology Daewoong Pharm. Co., Ltd.) ;
  • Yoo, Eun-Sook (Institute of Bioscience ＆ Biotechnology Daewoong Pharm. Co., Ltd.) ;
  • Byun, Young-Seok (Institute of Bioscience ＆ Biotechnology Daewoong Pharm. Co., Ltd.) ;
  • Park, Myung-Hwan (Institute of Bioscience ＆ Biotechnology Daewoong Pharm. Co., Ltd.)
  • Published : 2002.04.01
Download PDF
⟨ Previous Next ⟩

Abstract

This study describes the synthesis and in vitro evaluation of 2-[3- (Cyclopenthloxy) 4-Methoxyphenyl] - Substituted-1-Isoindolinone derivatives substituted on benzene moiety of isoindoline ring for the inhibition of $TNF-{\alpha}$ production. From this study, we have found the 6-C position on isoindolinone ring is an optimal derivatization site. Among the compounds synthesized, 6-ammo-2-[3-(cyclopentyloxy)-4-methoxyphenyl]-1-isoindolinone (6) was the most potent in inhibitory activity of $TNF-{\alpha}$ production in LPS-stimulated RAW264.7 cells.

Keywords

References

  1. Baik, K., Yoo, E., Byun, Y., Lee, S., Jang, B., Son, H., Lee, J., Cho, J., Lee, S., Moon, S., Park, J., and Lee, B. Novel 3,4-dialkoxyphenylderivatives and their toerapeutic use thereof. Patent: W09842666, 1998
  2. Cho, J. Y., Park, J., Yoo, E. S., Yoshkawa, K., Baik, K. U., Lee, J. S. and Park, M. H. Inhibitory effect of lignans from the rhizomes of Coptis japonica var. dissecta on tumor necrosis factor-alpha production in lipopolysaccharide-stimulated RAW264.7 cells. Arch. Pharm. Res., 21,12-16 (1998) https://doi.org/10.1007/BF03216746
  3. Cho, J. Y., Park, J., Son, H. J., Park, J. S., Yoo, E. S., Baik, K. U., and Park, M. H. Effects of dialkoxylphenyl compounds with oxime group on activated macrophages and lymphocytes. Submitted (2001)
  4. Eigler A., Sinha B., Hartmann G., Endres S. Taming TNF: strategies to restrain this proinflammatory cytokine. Immunology Today, 18, 487-492 (1997)
  5. Espat, N. J., Copeland, E. M. and Moldawer, L. L. Tumor necrosis factor and cachexia: a current perspective. Surg. Oncol., 3, 255-262 (1994) https://doi.org/10.1016/0960-7404(94)90027-2
  6. Garrison, L. and McDonnell, N. D. Etanercept: therapeutic use in patients with rheumatoid arthritis. Ann. Rheum. Dis., Suppl 1, 165-169 (1999)
  7. Harriman, G., Harper, L. K. and Schaible, T. F. Summary of clinical trials in rheumatoid arthritis using infliximab, an anti-TNF alpha treatment. Ann. Rheum. Dis., Suppl 1, 161-164 (1999)
  8. Jones, R. E. and Moreland, L.W. Tumor necrosis factor inhibitors for rheumatoid arthritis. Bull. Rheum. Dis., 48, 1-4 (1999)
  9. Kubicki, M., Borowiak, T., Antkowiak W. The Effect of Different Hydrogen Bonding Schemes on Melting Points of Two Isomeric 2-Hydroxy-bomane-3-carboxylic Acids. Z. Naturforsch. B, 55, 671- 676 (2000)
  10. Muller, G. W., Shire, M. G., Wong, H., Corral, L. G., Patterson, R. T., Chen, y. and Stirling, D. I. Thalidomide analogs and PDE4 inhibition. Bioorg. Med. Chem. Lett., 8, 2669-2674 (1998) https://doi.org/10.1016/S0960-894X(98)00475-2
  11. Newton, R. C. and Decicco, C. P. Therapeutic Potential and Strategies for Inhibiting Tumor Necrosis Factor-$\alpha$. J. Med. Chem., 42, 2295-2314 (1999) https://doi.org/10.1021/jm980541n
  12. Park, J. S., Baik, K. U., Son, H. J., Cho, J. Y., Park, J., Lee, J. H., Lee, S. J., Yoo, E. S., Park, M. H. Syntheses and biological evaluation of novel compounds for the inhibition of TNF-$\alpha$ production. Kar. J. Med. Chem., 10, 6-9 (2000a)
  13. Park, J. S., Baik, K. U., Son, H. J., Cho, J. Y., Park, J., Lee, J. H., Lee, S. J., Yoo, E. S., Byun, Y. S., Park, M. H. Synthesis and structure-activity relationships of novel compounds for the inhibition of TNF-$\alpha$ production. Arch. Pharm. Res., 23, 332-337 (2000b) https://doi.org/10.1007/BF02975443
  14. Thomas P., Zofia, U., Ruth, J., Margaret, E.. Hydrogen-Bond Formation in Nitroanilines: The First Step in Designing Acentric Materials. J. Am. Chem. Soc., 109,7786-7797 (1987) https://doi.org/10.1021/ja00259a030
  15. van de Putte, LBA, Rau, R., Breedveld, F. One year efficacy results of the fully human anti-TNF antibody D2E7 in rheumatoid arthritis. Program and abstracts from the 64th Annual Scientific Meeting of the American College of Rheumatology, Philadelphia, Pennsylvania. Abstract 1218 (2000)