公开(公告)号：US20060223180A1

公开(公告)日：2006-10-05

申请号：US11446390

申请日：2006-06-02

申请人： Gary Bridger ,  Michael Abrams ,  Geoffrey Henson ,  Ronald MacFarland ,  Gary Calandra ,  Hal Broxmeyer ,  David Dale

发明人： Gary Bridger ,  Michael Abrams ,  Geoffrey Henson ,  Ronald MacFarland ,  Gary Calandra ,  Hal Broxmeyer ,  David Dale

IPC分类号： A61K31/33 ,  C12N5/08

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。 这些化合物的优选实施方案具有式<？in-line-formula description =“In-line Formulas”end =“lead”？> Z-linker-Z'（1）<？in-line-formula description =“ 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，所述氮原子彼此分开至少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/或可以与另外的环系稠合; 或Z具有下式：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'可以以上述Z所定义的形式实施，或 可替代地可以是公式<？in-line-formula description =“In-line Formulas”end =“lead”？> - N（R） - （CR <2> 其中每个R独立地是H或直链，支链或环状的烷基（1-6C），n是1或者 2，X为芳环，包括杂芳环，或为硫醇; “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：US20060193826A1

公开(公告)日：2006-08-31

申请号：US11269773

申请日：2005-11-08

申请人： Gary Bridger ,  Michael Abrams ,  Geoffrey Henson ,  Ronald MacFarland ,  Gary Calandra ,  Hal Broxmeyer ,  David Dale

发明人： Gary Bridger ,  Michael Abrams ,  Geoffrey Henson ,  Ronald MacFarland ,  Gary Calandra ,  Hal Broxmeyer ,  David Dale

IPC分类号： A61K38/19 ,  A61K31/551 ,  A61K31/33

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 N 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。 这些化合物的优选实施方案具有式<？in-line-formula description =“In-line Formulas”end =“lead”？> Z-linker-Z'（1）<？in-line-formula description =“ 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，所述氮原子彼此分开至少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/或可以与另外的环系稠合; 或Z具有式N，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所定义的形式实施， 或者可以具有公式<？in-line-formula description =“In-line Formulas”end =“lead”？> - N（R） - （CR 2 2 N）n 其中每个R独立地为H或直链，支链或环状的烷基（1-6C），n为1，其中每个R独立地为H或直链，支链或环状的烷基（1-6C） 或2，X是芳环，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：US20080063624A1

公开(公告)日：2008-03-13

申请号：US11841837

申请日：2007-08-20

申请人： Gary Bridger ,  Michael Abrams ,  Geoffrey Henson ,  Ronald Macfarland ,  Gary Calandra ,  Hal Broxmeyer ,  David Dale

发明人： Gary Bridger ,  Michael Abrams ,  Geoffrey Henson ,  Ronald Macfarland ,  Gary Calandra ,  Hal Broxmeyer ,  David Dale

IPC分类号： A61K31/395 ,  A61K31/4427 ,  A61K38/19 ,  A61P9/00

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; 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。 这些化合物的优选实施方案具有式<？in-line-formula description =“In-line Formulas”end =“lead”？> Z-linker-Z'（1）<？in-line-formula description =“ 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，所述氮原子彼此分开至少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/或可以与另外的环系稠合; 其中A包含含有至少一个N的单环或双环稠环体系，B是H或1-20个原子的有机部分，Z'可以以上述Z所定义的形式实施，或者可以是式 <？in-line-formula description =“In-line Formulas”end =“lead”？> - N（R） - （CR 2）N < 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：US20050043367A1

公开(公告)日：2005-02-24

申请号：US10456942

申请日：2003-06-05

申请人： Gary Bridger ,  Michael Abrams ,  Geoffrey Henson ,  Ronald MacFarland ,  Gary Calandra

发明人： Gary Bridger ,  Michael Abrams ,  Geoffrey Henson ,  Ronald MacFarland ,  Gary Calandra

IPC分类号： A61K31/33 ,  A61K31/496 ,  A61K31/55 ,  A61K31/551 ,  A61K31/555 ,  A61K38/00 ,  A61K38/19 ,  A61K31/44 ,  A61K31/137 ,  A61K31/40

CPC分类号： A61K31/33 ,  A61K31/496 ,  A61K31/55 ,  A61K31/551 ,  A61K31/555 ,  A61K38/193 ,  A61K38/195 ,  A61K47/555 ,  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 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′ is of the formula —Ar(Y)j;wherein Ar is an aromatic or heteroaromatic moiety, and each Y is independently a non-interfering substituent and j is 0-3; and “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具有下式：其中A包含含有至少一个N的单环或双环稠环体系，B是H或 有机部分为1-20个原子，Z'为-Ar（Y）j; 其中Ar是芳族或杂芳族部分，并且每个Y独立地是非干扰性取代基，并且j是0-3; 和“接头”表示键，亚烷基（1-6C）或可包含芳基，稠合芳基，亚烷基链中所含的氧原子，或可含有酮基或氮或硫原子。

公开(公告)号：US20070015780A1

公开(公告)日：2007-01-18

申请号：US10548794

申请日：2004-03-10

申请人： Donald Picker ,  Geoffrey Henson ,  Simon Fricker ,  Kunwar Shailubhai ,  Gary Jacob

发明人： Donald Picker ,  Geoffrey Henson ,  Simon Fricker ,  Kunwar Shailubhai ,  Gary Jacob

IPC分类号： A61K31/4747 ,  A61K31/403

CPC分类号： A61K31/403 ,  A61K31/438 ,  A61K31/454 ,  A61K31/4747 ,  A61K45/06 ,  A61K2300/00

摘要： A method of treating cancer by administering a therapeutically effective amount of a compound represented by the following Formula (I), or salt, hydrate, or solvate thereof; wherein: n represents a number from 3 to 7; m represents a number from 1 to 2; R1 and R2 independently represent a hydrogen atom or are a substituted or unsubstituted, branched or unbranched or cyclic, alkyl provided that the total number of carbon atoms represented by R1 and R2 when taken together is no less than 5 and no greater than 10; or R1 and R2 together independently represent a cyclic alkyl group having no less than 3 or no more than 7 carbon atoms; R3 and R4 independently represent a hydrogen atom or a saturated or unsaturated, substituted or unsubstituted, branched or unbranched or cyclic, hydrocarbyl radical.

摘要翻译： 通过施用治疗有效量的由下式（I）表示的化合物或其盐，水合物或溶剂合物来治疗癌症的方法; 其中：n表示3〜7的数; m表示1〜2的数; R 1和R 2独立地表示氢原子，或者是取代或未取代的，支链或非支链或环状烷基，条件是由R 1表示的碳原子总数， 当共在一起时，SUB> 1和R 2 2不小于5且不大于10; 或R 1和R 2共同独立地表示具有不少于3个或不超过7个碳原子的环状烷基; R 3和R 4独立地表示氢原子或饱和或不饱和的取代或未取代的支链或非支链或环状烃基。

公开(公告)号：US20050250801A1

公开(公告)日：2005-11-10

申请号：US10796292

申请日：2004-03-10

申请人： Kunwar Shailubhai ,  Gary Jacob ,  Donald Picker ,  Geoffrey Henson ,  Simon Fricker

发明人： Kunwar Shailubhai ,  Gary Jacob ,  Donald Picker ,  Geoffrey Henson ,  Simon Fricker

IPC分类号： A61K20060101 ,  A61K31/403 ,  A61K31/438 ,  A61K31/454 ,  A61K31/4747 ,  A61K38/00 ,  A61K45/06

CPC分类号： A61K31/403 ,  A61K31/438 ,  A61K31/454 ,  A61K31/4747 ,  A61K45/06 ,  A61K2300/00

摘要： A method of treating cancer by administering a therapeutically effective amount of a compound represented by the following Formula (I), or salt, hydrate, or solvate thereof: wherein: n represents a number from 3 to 7; m represents a number from 1 to 2; R1 and R2 independently represent a hydrogen atom or are a substituted or unsubstituted, branched or unbranched or cyclic, alkyl provided that the total number of carbon atoms represented by R1 and R2 when taken together is no less than 5 and no greater than 10; or R1 and R2 together independently represent a cyclic alkyl group having no less than 3 or no more than 7 carbon atoms; R3 and R4 independently represent a hydrogen atom or a saturated or unsaturated, substituted or unsubstituted, branched or unbranched or cyclic, hydrocarbyl radical.

摘要翻译： 通过给予治疗有效量的由下式（I）表示的化合物或其盐，水合物或溶剂合物来治疗癌症的方法：其中：n表示3至7的数; m表示1〜2的数; R 1和R 2独立地表示氢原子，或者是取代或未取代的，支链或非支链或环状烷基，条件是由R 1表示的碳原子总数， 当共在一起时，SUB> 1和R 2 2不小于5且不大于10; 或R 1和R 2共同独立地表示具有不少于3个或不超过7个碳原子的环状烷基; R 3和R 4独立地表示氢原子或饱和或不饱和的取代或未取代的支链或非支链或环状烃基。