Synthesis and biological activities of NB-506 analogues: Effects of the positions of two hydroxyl groups at the indole rings

被引:28
作者
Ohkubo, M [1 ]
Nishimura, T [1 ]
Honma, T [1 ]
Nishimura, I [1 ]
Ito, S [1 ]
Yoshinari, T [1 ]
Arakawa, H [1 ]
Suda, H [1 ]
Morishima, H [1 ]
Nishimura, S [1 ]
机构
[1] Merck Res Labs, Banyu Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan
关键词
anticancer agents; topoisomerase; indolocarbazole; substituent effects;
D O I
10.1016/S0960-894X(99)00595-8
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
In the course of a study of 6-N-amino-substituted analogues of NB-506 (1), a more potent anticancer drug, J-109,404 (2), in which the formyl group of NB-506 was replaced with a 1,3-dihydroxypropane group, was reported. A study of further modification in the positions of two hydroxyl groups at the indole rings of 2 resulted in the discovery of a 2,10-dihydroxy analogue, J-107,088 (3), which is a promising anticancer agent with a broader therapeutic window than J-109,404. (C) 1999 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:3307 / 3312
页数:6
相关论文
共 11 条
  • [1] ARAKAWA H, 1995, CANCER RES, V55, P1316
  • [2] ARAKAWA H, 1999, IN PRESS JAP J CANC
  • [3] Fukasawa K, 1998, INT J CANCER, V75, P145, DOI 10.1002/(SICI)1097-0215(19980105)75:1<145::AID-IJC22>3.0.CO
  • [4] 2-E
  • [5] A NEW ANTITUMOR SUBSTANCE, BE-13793C, PRODUCED BY A STREPTOMYCETE - TAXONOMY, FERMENTATION, ISOLATION, STRUCTURE DETERMINATION AND BIOLOGICAL-ACTIVITY
    KOJIRI, K
    KONDO, H
    YOSHINARI, T
    ARAKAWA, H
    NAKAJIMA, S
    SATOH, F
    KAWAMURA, K
    OKURA, A
    SUDA, H
    OKANISHI, M
    [J]. JOURNAL OF ANTIBIOTICS, 1991, 44 (07) : 723 - 728
  • [6] Morham SG, 1996, MOL CELL BIOL, V16, P6804
  • [7] Synthesis and biological activities of topoisomerase I inhibitors, 6-N-amino analogues of NB-506
    Ohkubo, M
    Kojiri, K
    Kondo, H
    Tanaka, S
    Kawamoto, H
    Nishimura, T
    Nishimura, I
    Yoshinari, T
    Arakawa, H
    Suda, H
    Morishima, H
    Nishimura, S
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1999, 9 (09) : 1219 - 1224
  • [8] Synthesis of dissymmetric indolocarbazole glycosides using the Mitsunobu reaction at the glycosylation step
    Ohkubo, M
    Nishimura, T
    Jona, H
    Honma, T
    Ito, S
    Morishima, H
    [J]. TETRAHEDRON, 1997, 53 (17) : 5937 - 5950
  • [9] Synthesis of NB-506, a new anticancer agent
    Ohkubo, M
    Kawamoto, H
    Ohno, T
    Nakano, M
    Morishima, H
    [J]. TETRAHEDRON, 1997, 53 (02) : 585 - 592
  • [10] Yoshinari T, 1999, CANCER RES, V59, P4271