Biologically active spermidine analogues, pharmaceutical compositions and methods of treatment
申请人:——
公开号:US20020045780A1
公开(公告)日:2002-04-18
Polyamines having the formula:
1
or a salt thereof with a pharmaceutically acceptable acid wherein: R
1
-R
5
may be the same or different and are alkyl, aryl, aryl alkyl, cycloalkyl or hydrogen; at least one of R
1
and R
2
and at least one of R
4
and R
5
are not hydrogen, and any of the alkyl chains may optionally be interrupted by at least one etheric oxygen atom, excluding N
1
,N
3
-diethylspermidine and N
1
,N
3
-dipropylspermidine; and
A and B are bridging groups which effectively maintain the distance between the nitrogen atoms such that the polyamine: (i) is capable of uptake by a target cell upon administration of the polyamine to a human or non-human animal; and (ii) upon uptake by the target cell, competitively binds via an electrostatic interaction between the positively charged nitrogen atoms to substantially the same biological counter-anions as the intracellular natural polyamines in the target cell.
具有以下公式1或其药学上可接受的酸盐的多胺,其中:R1-R5可以相同或不同,且为烷基,芳基,芳基烷基,环烷基或氢;R1和R2中至少有一个,以及R4和R5中至少有一个不是氢,任何烷基链都可以选择性地被至少一个醚氧原子中断,但不包括N1,N3-二乙基亚精胺和N1,N3-二丙基亚精胺;A和B是桥接基团,有效地保持氮原子之间的距离,使得多胺:(i)在将多胺用于人类或非人类动物的治疗时,能够被目标细胞吸收;(ii)在被目标细胞吸收后,通过正电荷氮原子之间的静电相互作用与目标细胞中的细胞内天然多胺基本相同地竞争性结合生物计数离子。