항진균제로서 Cycloalkylcarbamoyl이 치환된 Detoconazole 유도체 합성

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Journal of the Korean Industrial and Engineering Chemistry, Vol.6, No.3, 475-481, June, 1995

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항진균제로서 Cycloalkylcarbamoyl이 치환된 Detoconazole 유도체 합성

Synthesis of Cycloalkylcarbamoyl Substituted Ketoconazole Derivatives as Antifungal Agents

류성렬

초록

새로운 항진균11를 합성하기 위하여 cis-4-[4-[[2-(2,4-dichlorophenyl)-2-(lH-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenol]piperazine(15)과 N-cycloalkylcarbamoyl 유도체인 N-cyclopropyl-2-chloroacetamide와 N-cyclohexyl-2-chloroacetamide를 반응시켜 치환기인(R=cyclopropyl, cyclohexyl)이가 도입된 2개의 새로운 유도체인 cis-1-(N-cycloalkyl substituted carbamoyl)-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazine을 합성하였다.

In an effort of the synthesis of new antifungal agent, two new cis-1-(N-cycloalkyl substituted carbamoyl)-4-[4-[[2-(2,4-dichlorophenyl)-2-(1-Η-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazine derivatives(R=cyclopropyl, cyclohexyl) were synthesized by the reaction of cis-4-[4-[[2-(2,4-dichlorophenyl)-2-(1Η-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazine with Ν-cycloalkylcarbamoyl substituted derivatives.

[References]

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Buchel KH, Draber W, Regel E, Plempel M, Arzeim-Forsch., 22, 1260 (1972)
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vanCutsem J, Thienpont D, Treatment of Crop Candidosis in Turkeys with R 41 400, Preclinical Research Report R 41 400/1. Janssen Pharmaceutica, Beers, Belgium (1977)
vanCutsem J, Thienpont D, Oral Treatment with R41 400 of Systemic Candidosis in Chickens, Preclinical Research R41 400/6, Janssen Pharmaceutica, Beers, Belgium (1977)
Heeres J, Backx LJJ, Mostmans JH, VanCutsem J, J. Med. Chem., 22, 1003 (1979)
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Janssen PAJ, New Antifungal Agents, A Rsut of Target-Oriented Drug Design, 29 (1978)
Vanden Bossche H, Willemsens G, Cools W, Lauwers W, Marichal P, Cornelissen F, Pestic. Sci., 15, 188 (1984)
VandenBossche H, Bellens D, Cools W, Gorrens J, Marichal P, Verhoeven H, Willemsens G, DeCoster R, Lauwers W, Jeune L, Drug Dev. Res., 8, 287 (1986)
Henry MJ, Sisler HD, Antimicob. Agents Chemother., 15, 603 (1979)
Takeuchi I, Yamamoto K, Ito T, Hamada Y, Yakugaku Zasshi, 106, 567 (1986)
Heeres J, U.S. Patent, 3,936,470 (1976)
Takeuchi HI, Yamamoto K, Hirota M, Suesawa H, Chem. Pharm. Bull., 32, 302 (1984)
Suesawa H, Hirota M, Yamamoto K, Takeuchi I, Hamaada Y, Bull. Chem. Soc. Jpn., 57, 883 (1984)
Italy Camillo Corvi SpA BE 850,628; U.S. Patent, 4,278,796 (1986)

[1] Beneke ES, Rogers AL, "Medical Mycology," 4th. Ed., 1-8, Burgess Pub. Co. (1980)

[2] Finegold SM, Baron EJ, Baily, "Scotts Diagnostic Mincrobiology," 7th Ed., 678-774, The C.V. Mosby Co. (1986)

[3] Holt RJ, Drugs, 9, 401 (1972)

[4] Goderfori EF, Janssen PAJ, vanderEycken CAM, vanHeertum AHMT, Niemegeers CJE, J. Med. Chem., 8, 220 (1965)

[5] Godefori EF, vanCustsem J. VanderEycken CAM, Janssen PAJ, J. Med. Chem., 10, 1160 (1967)

[6] Vanbreusegham R, vanCutsem J, Thienpont D, Chemotherapy, 12, 107 (1967)

[7] vanCutsem J, Thienpont D, Chemotherapy, 17, 392 (1972)

[8] Bennett JE, Annu. Int. Med., 73, 653 (1970)

[9] Buchel KH, Draber W, Regel E, Plempel M, Arzeim-Forsch., 22, 1260 (1972)

[10] Holt RJ, Drugs, 9, 401 (1975)

[11] vanCutsem J, Thienpont D, Treatment of Crop Candidosis in Turkeys with R 41 400, Preclinical Research Report R 41 400/1. Janssen Pharmaceutica, Beers, Belgium (1977)

[12] vanCutsem J, Thienpont D, Oral Treatment with R41 400 of Systemic Candidosis in Chickens, Preclinical Research R41 400/6, Janssen Pharmaceutica, Beers, Belgium (1977)

[13] Heeres J, Backx LJJ, Mostmans JH, VanCutsem J, J. Med. Chem., 22, 1003 (1979)

[14] Borgers M, "The Scientific Basis of Antimicrobial Chemotherapy," ed. D. Greenwood and F. O'Grady, 133 Cambridge University Press, Cambridge (1985)

[15] Janssen PAJ, New Antifungal Agents, A Rsut of Target-Oriented Drug Design, 29 (1978)

[16] Vanden Bossche H, Willemsens G, Cools W, Lauwers W, Marichal P, Cornelissen F, Pestic. Sci., 15, 188 (1984)

[17] VandenBossche H, Bellens D, Cools W, Gorrens J, Marichal P, Verhoeven H, Willemsens G, DeCoster R, Lauwers W, Jeune L, Drug Dev. Res., 8, 287 (1986)

[18] Henry MJ, Sisler HD, Antimicob. Agents Chemother., 15, 603 (1979)

[19] Takeuchi I, Yamamoto K, Ito T, Hamada Y, Yakugaku Zasshi, 106, 567 (1986)

[20] Heeres J, U.S. Patent, 3,936,470 (1976)

[21] Takeuchi HI, Yamamoto K, Hirota M, Suesawa H, Chem. Pharm. Bull., 32, 302 (1984)

[22] Suesawa H, Hirota M, Yamamoto K, Takeuchi I, Hamaada Y, Bull. Chem. Soc. Jpn., 57, 883 (1984)

[23] Italy Camillo Corvi SpA BE 850,628; U.S. Patent, 4,278,796 (1986)