Studies on the Synthesis of Etodolac Derivatives as Potential Anti-inflammatory Agents

항염증제인 Etodolac 유도체의 합성에 관한 연구

  • Cho, Hoon (Department of Chemistry, Chungbuk National University) ;
  • Chung, Yong Seog (Department of Chemistry, Chungbuk National University) ;
  • Jang, Hang Dong (Department of Chemical Engineering, Seoul National Polytechnic University) ;
  • Ryu, Seong Ryual (Department of Chemical Engineering, Dae Bul University)
  • 조훈 (충북대학교 화학과) ;
  • 정용석 (충북대학교 화학과) ;
  • 장향동 (서울산업대학교 화학공학과) ;
  • 류성렬 (대불대학교 화학공학과)
  • Received : 1998.08.24
  • Accepted : 1998.09.25
  • Published : 1999.02.10

Abstract

For the synthesis of new anti-inflammatory agents as indol derivatives, we have synthesized ${\alpha}$-benzoyl-1-ethyl-1,3,4,9-tetrahydro-8-ethyl-9-(N-benzoyl)pyrano[3,4-b]indole-1-acetic acid methyl ester. It was a new method for ${\alpha}$-substituted etodolac carboxylic acid. The synthetic process was composed of four steps, and 7-ethylindole and oxalyl chloride were used as starting materials. The third step, cyclization was carried out by addition of borontrifluoride diethyl etherate in 66% yield. The step of reduction and cyclization were simplified successfully. The final product, ${\alpha}$-benzoyl-1-ethyl-1,3,4,9-tetrahydro-8-ethyl-9-(N-benzoyl)pyrano[3,4-b]indole-1-acetic acid methyl ester was obtained in 66% yield by the reaction of methyl 1,8-dimethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetate (etodollic acid methyl ester) and benzoyl chloride.

References

  1. Brit. Med. J. v.2 D. L. Beales;H. C. Burry;R. Grahame
  2. Brit. Med. J. v.2 D. N. Croft;J. H. P. Cuddigan;C. Sweetland
  3. J. Int. Med. Res. v.1 Drug profile: Benoral J. E. Murphy
  4. Belgium patent, 867,760 [CA 90, 121413d] A. G. Sterwin
  5. Spain patent, 411, 400,[CA 87, p 52958] A. S. A. Gallardo
  6. Phamacologist v.18 D. C. Hobbs;T. M. Twomey
  7. JPA 42-23418
  8. Fed. Proc., Fed. Am. Soc. Exp. Biol. v.31 T. Y. Shen;B. E. Witzel;H. Jones;B. O. Linn;J. McPherson;R. Greenwald;M. Fordice;A. Jacobs
  9. Fed. Proc., Fed. Am. Soc. Exp. Biol. v.31 C. G. Van Arman;E. A. Risley;G. W. Nuss
  10. Chem. Iisty. v.51 J. Novak;J. Ratusky;V. Sneberg;F. Sorm
  11. USP 3, 161, 654
  12. J. Org. Chem. v.46 Eric J. Nordlander;David B. Catalane;Kirtivan D. Kotian;Randall M. Stevens;Jerome E. Haky
  13. J. M. C. v.19 Christopher A. Demerson;Leslie G. Humber;Adolf H. Philipp.
  14. J. M. C. v.18 Christopher A. Demerson;Leslie G. Humber;Thomas A. Dobson