항염증제인 Etodolac 유도체의 함성에 관한 연구

조훈; 정용석; 장향동; 류성렬

Journal of the Korean Industrial and Engineering Chemistry, Vol.10, No.1, 135-137, February, 1999

Export Citation

항염증제인 Etodolac 유도체의 함성에 관한 연구

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

조훈, 정용석, 장향동, 류성렬

초록

새로운 인돌 유도체인 항염증제를 합성하기 위하여 α-benzoyl-1-ethyl-1,3,4,9-tetrahydro-8-ethyl-9-(N-benzoyl)pyrano[3,4-b]indole-1-acetic acid methyl ester(10)을 합성하였다. 출발물질은 7-ethylindole과 oxalyl chloride로 하여 4단계로 이루어졌다. 셋째 단계는 borontrifluoride diethyl etherate을 사용하여 66%로 고리화반응을 하였으며, 환원반응과 고리화반응도 효율적으로 단순화하였다. 최종생성물인 α-benzoyl-1-ethyl-1,3,4,9-tetrahydro-8-ethyl-9-(N-benzoyl)pyrano[3,4-b]indole-1-acetic acid methyl ester는 4단계에서 얻은 methyl 1,8-dimethyl-1,3,4,9-tetrahydropyrano[3,4-b] indole-1-acetate(etodollic acid methyl ester)를 benzoyl chloride와 반응하여 66%의 수율로 얻었다.

For the synthesis of new anti-inflammatory agents as indol derivatives, we have synthesized α-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 α-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, α-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.

Keywords:The Synthesis of Etodolac Derivatives

[References]

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[1] Beales DL, Burry HC, Grahame R, Brit. Med. J., 2, 483 (1972)

[2] Croft DN, Cuddigan JHP, Sweetland C, Brit. Med. J., 2, 545 (1972)

[3] Murphy JE, J. Int. Med. Res., 1, 65 (1972)

[4] Sterwin AG, Belgium Patent, 867,760, [CA 90, 121413d] (1978)

[5] Gallardo ASA, Spain Patent, 411,400, [CA 87, p 52958] (1976)

[6] Hobbs DC, Twomey TM, Pharmacologist, 18, 152 (1976)

[7] Japan Patent, 42-23418 (1967)

[8] Shen TY, Witzel BE, Jones H, Linn BO, McPherson J, Greenwald R, Fordice M, Jacobs A, Van Arman CG, Risley EA, Nuss GW, Fed. Proc. Fed. Am. Soc. Exp. Biol., 31, 577 (1972)

[9] Novak J, Ratusky J, Sneberg V, Sorm F, Chem. Listy., 51, 479 (1957)

[10] U.S. Patent, 3,161,654 (1964)

[11] Nordlander EJ, Catalane DB, Kotian KD, Stevens RM, Haky JE, J. Org. Chem., 46, 779 (1981)

[12] Demerson CA, Humber LG, Philipp AH, J. Med. Chem., 19, 391 (1976)

[13] Demerson CA, Humber LG, Dobson TA, J. Med. Chem., 18, 189 (1975)