公开(公告)号：EP0496634A1

公开(公告)日：1992-07-29

申请号：EP92300618.3

申请日：1992-01-24

Applicant: GLAXO INC.

Inventor： Luzzio, Michael J. ,  Besterman, Jeffrey M. ,  Evans, Michael G. ,  Johnson, Ross M.

IPC: C07D491/056 ,  A61K31/47

CPC classification number: C07D491/04

Abstract: The present invention relates to the compounds of formula (I),

wherein:
   R¹ is hydrogen, hydroxy or amino;
   R² is hydrogen, hydroxy, methoxy or methoxymethoxy;
   R³ is hydrogen, hydroxy, amino, methoxy, methoxymethoxy or, taken together with R², methylenedioxy (also known as 1,3 dioxolo);
   R⁴ is hydrogen, hydroxy, methoxy, methoxymethoxy, benzyl, di(C₁₋₄)alkylaminomethyl or, taken together with R³, methylenedioxy;
   R⁵ is hydrogen or hydroxy;
provided that at least one of R¹ through R⁵ is other than hydrogen; and


i) X² is hydroxy or methoxy with X¹, X³ and X⁴ being hydrogen; or
ii) X¹ taken together with X²,
   X² taken together with X³ or
   X³ taken together with X⁴, is methylenedioxy, provided that each of the remaining respective X¹, X², X³ and X⁴ substituents are hydrogen,
intermediates in the synthesis of them, pharmaceutical formulation containing them, their use as inhibitors of topoisomerase and their use in the treatment of tumors.

Abstract translation: 本发明涉及式（I）化合物，其中：R 1是氢，羟基或氨基; R 2是氢，羟基，甲氧基或甲氧基甲氧基; R 3为氢，羟基，氨基，甲氧基，甲氧基甲氧基，或与R 2一起亚甲二氧基（也称为1,3-二氧杂环戊烷）一起使用。 R 4是氢，羟基，甲氧基，甲氧基甲氧基，苄基，二（C1-4）烷基氨基甲基或与R 3一起亚甲二氧基; R 5是氢或羟基; 条件是R 1至R 5中的至少一个不是氢; 和i）X 2是羟基或甲氧基，X 1，X 3和X 4是氢; 或ii）与X 2一起X，X 2与X 3或X 3一起与X 4一起使用的X 1是亚甲二氧基，条件是剩余的各自的X X 1，X 3和X 4取代基是氢，它们的合成中的中间体，含有它们的药物制剂，它们作为拓扑异构酶的抑制剂的用途及其在治疗肿瘤中的用途。