申请人:——
公开号:US20030130250A1
公开(公告)日:2003-07-10
Methods to elevate progenitor and stem cell counts in animal subjects using compounds which bind to the chemokine receptor CXCR4 are disclosed. Preferred embodiments of such compounds are of the formula
Z-linker-Z′ (1)
or pharmaceutically acceptable salt thereof
wherein Z is a cyclic polyamine containing 9-32 ring members of which 3-8 are nitrogen atoms, said nitrogen atoms separated from each other by at least 2 carbon atoms, and wherein said heterocycle may optionally contain additional heteroatoms besides nitrogen and/or may be fused to an additional ring system;
or Z is of the formula
1
wherein A comprises a monocyclic or bicyclic fused ring system containing at least one N and B is H or an organic moiety of 1-20 atoms,
Z′ may be embodied in a form as defined by Z above, or alternatively may be of the formula
—N(R)—(CR
2
)
n
—X
wherein each R is independently H or straight, branched or cyclic alkyl (1-6C), n is 1 or 2, and X is an aromatic ring, including heteroaromatic rings, or is a mercaptan;
“linker” represents a bond, alkylene (1-6C) or may comprise aryl, fused aryl, oxygen atoms contained in an alkylene chain, or may contain keto groups or nitrogen or sulfur atoms.
公开了一种使用与趋化因子受体CXCR4结合的化合物来提高动物主体和干细胞数量的方法。这些化合物的首选实施例为以下公式所示:Z-连接物-Z′(1)或其药用盐,其中Z是含有9-32个环成员的环状多胺,其中3-8个是氮原子,所述氮原子彼此之间至少相隔2个碳原子,且所述杂环除了氮原子外还可以包含额外的杂原子和/或与额外的环系统融合;或者Z为以下公式1所示:其中A包括至少一个N的单环或双环融合环系统,B为H或1-20个原子的有机基团,Z'可以采用如上所定义的Z的形式,或者也可以是以下公式的形式:-N(R)-(CR2)n-X其中每个R独立地为H或直链、支链或环烷基(1-6C),n为1或2,X为芳香环,包括杂芳环,或者是硫醇;“连接物”代表键,烷基(1-6C)或可能包含芳基、融合芳基、含在烷基链中的氧原子,或者可能含有酮基团、氮原子或硫原子。