申请人:Szarek Walter
公开号:US20090099100A1
公开(公告)日:2009-04-16
Therapeutic compounds and methods for modulating amyloid aggregation in a subject, whatever its clinical setting, are described. Amyloid aggregation is modulated by the administration to a subject of an effective amount of a therapeutic compound of the formula
or a pharmaceutically acceptable salt or ester, such that modulation of amyloid aggregation occurs. R
1
and R
2
are each independently a hydrogen atom or a substituted or unsubstituted aliphatic or aryl group. Z and Q are each independently a carbonyl (C═O), thiocarbonyl (C═S), sulfonyl (SO
2
), or sulfoxide (S═O) group. “k” and “m” are 0 or 1, provided when k is 1, R
1
is not a hydrogen atom, and when m is 1, R
2
is not a hydrogen atom. In an embodiment, at least one of k or m must equal 1. “p” and “s” are each independently positive integers selected such that the biodistribution of the therapeutic compound for an intended target site is not prevented while maintaining activity of the therapeutic compound. T is a linking group and Y is a group of the formula -A X wherein A is an anionic group at physiological pH, and X is a cationic group.
本文描述了用于调节主体中淀粉样聚集物的治疗化合物和方法,无论其临床设置如何。通过向主体投予公式中的治疗化合物或其药学上可接受的盐或酯的有效量,从而调节淀粉样聚集物的聚集。其中,R1和R2分别独立地是氢原子或取代或未取代的脂肪族或芳香族基团。Z和Q分别独立地是羰基(C═O),硫代羰基(C═S),磺酰基(SO2)或亚砜基(S═O)基团。“k”和“m”均为0或1,当k为1时,R1不是氢原子,当m为1时,R2不是氢原子。在一种实施例中,k或m中至少有一个必须等于1。“p”和“s”分别独立地是正整数,选取这些正整数以便在维持治疗化合物的活性的同时,不会阻止治疗化合物对预期靶位点的生物分布。T是一个连接基团,而Y是一个公式为-A X的基团,其中A是生理pH下的阴离子基团,而X是一个阳离子基团。