公开(公告)号：US20170049747A1

公开(公告)日：2017-02-23

申请号：US15074836

申请日：2016-03-18

申请人： Genzyme Corporation

发明人： Gary J. BRIDGER ,  Michael J. ABRAMS ,  Geoffrey W. HENSON ,  Ronald Trevor MACFARLAND ,  Gary B. CALANDRA ,  Hal E. BROXMEYER ,  David C. DALE

IPC分类号： A61K31/395 ,  A61K35/28

CPC分类号： A61K31/395 ,  A61K31/33 ,  A61K31/4427 ,  A61K31/496 ,  A61K31/55 ,  A61K31/551 ,  A61K31/555 ,  A61K35/28 ,  A61K38/193 ,  A61K38/195 ,  A61K2035/124 ,  C12N5/0647 ,  A61K2300/00

摘要： 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 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)—(CR2)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.

摘要翻译： 公开了使用结合趋化因子受体CXCR4的化合物来提高动物受试者祖细胞和干细胞计数的方法。 这种化合物的优选实施方案是式Z-接头-Z'（1）或其药学上可接受的盐，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，所述氮原子彼此分离 至少2个碳原子，并且其中所述杂环可以任选地含有除氮之外的另外的杂原子和/或可以与额外的环系稠合; 或Z是式（a）的化合物，其中A包含含有至少一个N的单环或双环稠合环体系，B是H或1-20个原子的有机部分，Z'可以以Z定义的形式 或者可以是式-N（R） - （CR 2）n -X，其中每个R独立地为H或直链，支链或环状烷基（1-6C），n为1或2，X为 芳香环，包括杂芳环，或是硫醇; “接头”表示键，亚烷基（1-6C）或可包含亚烷基链中所含的芳基，稠合芳基，氧原子，或可含有酮基或氮或硫原子。

公开(公告)号：US20210161859A1

公开(公告)日：2021-06-03

申请号：US16927856

申请日：2020-07-13

申请人： Genzyme Corporation ,  University of Washington Center for Commercialization

发明人： David C. DALE ,  Gary J. BRIDGER ,  Frank J. HSU

IPC分类号： A61K31/395 ,  A61K38/19 ,  A61P7/06 ,  A61K45/06

摘要： Presently disclosed are methods and compositions for treating or preventing WHIM syndrome and certain other disorders or conditions with a certain CXCR4 antagonist.

公开(公告)号：US20190216773A1

公开(公告)日：2019-07-18

申请号：US16107761

申请日：2018-08-21

申请人： Genzyme Corporation

发明人： Gary J. BRIDGER ,  Michael J. ABRAMS ,  Geoffrey W. HENSON ,  Ronald Trevor MACFARLAND ,  Gary B. CALANDRA ,  Hal E. BROXMEYER ,  David C. DALE

IPC分类号： A61K31/395 ,  A61K31/555 ,  C12N5/0789 ,  A61K35/28 ,  A61K38/19 ,  A61K31/33 ,  A61K31/551 ,  A61K31/55 ,  A61K31/496 ,  A61K31/4427

CPC分类号： A61K31/395 ,  A61K31/33 ,  A61K31/4427 ,  A61K31/496 ,  A61K31/55 ,  A61K31/551 ,  A61K31/555 ,  A61K35/28 ,  A61K38/193 ,  A61K38/195 ,  A61K2035/124 ,  C12N5/0647 ,  A61K2300/00

摘要： 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 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)—(CR2)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.