申请人:Kitade Makoto
公开号:US20130296320A1
公开(公告)日:2013-11-07
Provided is a novel bicyclic compound which has an HSP90 inhibitory effect and a carcinostatic effect. Also provided is a pharmaceutical agent which is based on the HSP90 inhibitory effect and is useful in the prevention and/or treatment of a disease involving HSP90, particularly, cancer. The present invention provides a compound represented by the following general formula (I) or a salt thereof wherein at least one of X
1
, X
2
, X
3
, and X
4
represents N or N-oxide and the rest thereof are the same or different and each represent C—R
2
;
any one or two of Y
1
, Y
2
, Y
3
, and Y
4
represent C—R
4
and the rest thereof are the same or different and each represent CH or N;
R
1
represents an optionally substituted monocyclic or bicyclic unsaturated heterocyclic group having 1 to 4 heteroatoms selected from N, S, and O;
R
2
represents a hydrogen atom, an optionally substituted alkyl group having 1 to 6 carbon atoms etc.;
R
3
represents a hydrogen atom, —CO—R
5
etc.;
R
4
represents a hydrogen atom, —CO—R
6
, —N(R
7
)(R
8
) etc.;
R
5
represents a hydroxyl group, an amino group etc.;
R
6
represents a hydroxyl group etc.;
R
7
and R
8
are the same or different and each represent a hydrogen atom, an optionally substituted alkyl group having 1 to 6 carbon atoms etc.; and R
9
represents an optionally substituted cycloalkyl group having 3 to 7 carbon atoms etc.
提供了一种新颖的双环化合物,具有HSP90抑制作用和抗癌作用。还提供了一种基于HSP90抑制作用的药物剂,用于预防和/或治疗涉及HSP90的疾病,特别是癌症。本发明提供了以下一般式(I)所表示的化合物或其盐,其中X1、X2、X3和X4中的至少一个代表N或N-氧化物,其余部分相同或不同,每个代表C—R2;Y1、Y2、Y3和Y4中的任意一个或两个代表C—R4,其余部分相同或不同,每个代表CH或N;R1代表具有1至4个异原子(N、S和O)的可选择取代的单环或双环不饱和杂环基;R2代表氢原子、具有1至6个碳原子的可选择取代的烷基基团等;R3代表氢原子、—CO—R5等;R4代表氢原子、—CO—R6、—N(R7)(R8)等;R5代表羟基、氨基等;R6代表羟基等;R7和R8相同或不同,每个代表氢原子、具有1至6个碳原子的可选择取代的烷基基团等;R9代表具有3至7个碳原子的可选择取代的环烷基基团等。