公开(公告)号：US08716242B2

公开(公告)日：2014-05-06

申请号：US13513550

申请日：2009-12-04

申请人： Sophie Barthélémy ,  Christian Bisang ,  Frank Otto Gombert ,  Alexander Lederer ,  Daniel Obrecht ,  Barbara Romagnoli ,  Jürg Zumbrunn ,  Tobias Remus ,  Guillaume Lemercier

发明人： Sophie Barthélémy ,  Christian Bisang ,  Frank Otto Gombert ,  Alexander Lederer ,  Daniel Obrecht ,  Barbara Romagnoli ,  Jürg Zumbrunn ,  Tobias Remus ,  Guillaume Lemercier

IPC分类号： A61K38/12 ,  C07K7/08

CPC分类号： C07K7/08 ,  A61K38/00 ,  C07K7/64

摘要： β-Hairpin peptidomimetics of the general formula Cyclo(-Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Xaa9-Xaa10-Xaa11-Xaa12-Xaa13-Xaa14-Xaa15-Xaa16-), and pharmaceutically acceptable salts thereof, with Xaa 1-Xaa 16 being amino acid residues of certain types which are defined in the description and the claims, have CXCR4 antagonizing properties and prolonged half-lives in vivo and can be used for preventing HIV infections in healthy individuals or for slowing and halting viral progression in infected patients; or where cancer is mediated or resulting from CXCR4 receptor activity; or where immunological diseases are mediated or resulting from CXCR4 receptor activity; or for treating immunosuppression; or during apheresis collections of peripheral blood stem cells and/or as agents to induce mobilization of stem cells to regulate tissue repair. These peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

摘要翻译： （-Xaa1-Xaa2-Xaa3-Xaa4-Xaa8-Xaa6-Xaa7-Xaa8-Xaa9-Xaa10-Xaa11-Xaa12-Xaa13-Xaa14-Xaa15-Xaa16-）的通式肽模拟物及其药学上可接受的盐 其中Xaa 1-Xaa 16是在说明书和权利要求书中定义的某些类型的氨基酸残基，具有CXCR4拮抗特性和体内延长的半衰期，并且可用于预防健康个体的HIV感染或减缓 并阻止感染患者的病毒进展; 或由CXCR4受体活性介导或产生癌症; 或其中免疫性疾病介导或由CXCR4受体活性产生; 或用于治疗免疫抑制; 或在外周血干细胞的分离采集期间和/或作为诱导干细胞动员以调节组织修复的试剂。 这些肽模拟物可以通过基于混合固相和溶液相合成策略的方法制造。

公开(公告)号：US20120283196A1

公开(公告)日：2012-11-08

申请号：US13513550

申请日：2009-12-04

申请人： Sophie Barthélémy ,  Christian Bisang ,  Frank Otto Gombert ,  Alexander Lederer ,  Daniel Obrecht ,  Barbara Romagnoli ,  Jürg Zumbrunn ,  Tobias Remus ,  Guillaume Lemercier

发明人： Sophie Barthélémy ,  Christian Bisang ,  Frank Otto Gombert ,  Alexander Lederer ,  Daniel Obrecht ,  Barbara Romagnoli ,  Jürg Zumbrunn ,  Tobias Remus ,  Guillaume Lemercier

IPC分类号： C07K7/64 ,  C07K1/06 ,  A61K38/12

CPC分类号： C07K7/08 ,  A61K38/00 ,  C07K7/64

摘要： β-Hairpin peptidomimetics of the general formula Cyclo(-Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Xaa9-Xaa10-Xaa11-Xaa12-Xaa13-Xaa14-Xaa15-Xaa16-), and pharmaceutically acceptable salts thereof, with Xaa 1-Xaa 16 being amino acid residues of certain types which are defined in the description and the claims, have CXCR4 antagonizing properties and prolonged half-lives in vivo and can be used for preventing HIV infections in healthy individuals or for slowing and halting viral progression in infected patients; or where cancer is mediated or resulting from CXCR4 receptor activity; or where immunological diseases are mediated or resulting from CXCR4 receptor activity; or for treating immunosuppression; or during apheresis collections eases of peripheral blood stem cells and/or as agents to induce mobilization of stem cells to regulate tissue repair. These peptidomimetics can be manufactured by a process which is based on a mixed solid-and solution phase synthetic strategy.

摘要翻译： （-Xaa1-Xaa2-Xaa3-Xaa4-Xaa8-Xaa6-Xaa7-Xaa8-Xaa9-Xaa10-Xaa11-Xaa12-Xaa13-Xaa14-Xaa15-Xaa16-）的通式肽模拟物及其药学上可接受的盐 其中Xaa 1-Xaa 16是在说明书和权利要求书中定义的某些类型的氨基酸残基，具有CXCR4拮抗特性和体内延长的半衰期，并且可用于预防健康个体的HIV感染或减缓 并阻止感染患者的病毒进展; 或由CXCR4受体活性介导或产生癌症; 或其中免疫性疾病介导或由CXCR4受体活性产生; 或用于治疗免疫抑制; 或在血浆分离术收集期间减少外周血干细胞和/或作为诱导干细胞调动以调节组织修复的试剂。 这些肽模拟物可以通过基于混合固相和溶液相合成策略的方法来制造。

公开(公告)号：US20110245155A1

公开(公告)日：2011-10-06

申请号：US12828998

申请日：2010-07-01

申请人： Jürg Zumbrunn ,  Steven J. Demarco ,  Sergio Lociuro ,  Jan Wim Vrijbloed ,  Frank Gombert ,  Reshmi Mukherjee ,  Kerstin Moehle ,  Daniel Obrecht ,  John Anthony Robinson ,  Heiko Henze ,  Barbara Romagnoli ,  Christian Ludin

发明人： Jürg Zumbrunn ,  Steven J. Demarco ,  Sergio Lociuro ,  Jan Wim Vrijbloed ,  Frank Gombert ,  Reshmi Mukherjee ,  Kerstin Moehle ,  Daniel Obrecht ,  John Anthony Robinson ,  Heiko Henze ,  Barbara Romagnoli ,  Christian Ludin

IPC分类号： A61K38/12 ,  C07K7/00 ,  A61K38/10 ,  A61P31/18 ,  A61P35/00

CPC分类号： C07K7/64 ,  A61K38/00 ,  C07K1/047 ,  C07K7/08

摘要： Template-fixed β-hairpin peptidomimetics of the general formula (I) wherein Z is a template-fixed chain of 12, 14 or 18 α-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid), are Gly, NMeGly, Pro or Pip, or of certain types which, as the remaining symbols in the above formula, are defined in the description and the claims, and salts thereof, have CXCR4 antagonizing properties and can be used for preventing HIV infections in healthy individuals or for slowing and halting viral progression in infected patients; or where cancer is mediated or resulting from CXCR4 receptor activity; or where immunological diseases are mediated or resulting from CXCR4 receptor activity; or for treating immuno suppression; or during apheresis collections of peripheral blood stem cells. These β-hairpin peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

摘要翻译： 通式（I）的模板固定和半乳糖肽模拟物，其中Z是12,14或18个α-氨基酸残基的模板固定链，其取决于其在链中的位置（从N- 末端氨基酸）是Gly，NMeGly，Pro或Pip，或某些类型，其作为上述式中的其余符号在说明书和权利要求书及其权利要求书中定义及其盐具有CXCR4拮抗性质并且可以使用 用于预防健康个体的艾滋病毒感染或减缓和停止感染患者的病毒进展; 或由CXCR4受体活性介导或产生癌症; 或其中免疫性疾病介导或由CXCR4受体活性产生; 或用于治疗免疫抑制; 或在外周血干细胞的分离采集期间。 这些可以通过基于混合固相和溶液相合成策略的方法制造。

公开(公告)号：US07786078B2

公开(公告)日：2010-08-31

申请号：US10555088

申请日：2004-04-29

申请人： Jürg Zumbrunn ,  Steven J. Demarco ,  Sergio Lociuro ,  Jan Wim Vrijbloed ,  Frank Gombert ,  Reshmi Mukherjee ,  Kerstin Moehle ,  Daniel Obrecht ,  John Anthony Robinson ,  Heiko Henze ,  Barbara Romagnoli ,  Christian Ludin

发明人： Jürg Zumbrunn ,  Steven J. Demarco ,  Sergio Lociuro ,  Jan Wim Vrijbloed ,  Frank Gombert ,  Reshmi Mukherjee ,  Kerstin Moehle ,  Daniel Obrecht ,  John Anthony Robinson ,  Heiko Henze ,  Barbara Romagnoli ,  Christian Ludin

IPC分类号： A61K38/12

CPC分类号： C07K7/64 ,  A61K38/00 ,  C07K1/047 ,  C07K7/08

摘要： Template-fixed β-hairpin peptidomimetics of the general formula (I) wherein Z is a template-fixed chain of 12, 14 or 18 α-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid), are Gly, NMeGly, Pro or Pip, or of certain types which, as the remaining symbols in the above formula, are defined in the description and the claims, and salts thereof, have CXCR4 antagonizing properties. These β-hairpin peptidomimetics can be manufactured by a process which is based on a mixed solid—and solution phase synthetic strategy.

摘要翻译： 通式（I）的模板固定和半乳糖肽模拟物，其中Z是12,14或18个α-氨基酸残基的模板固定链，其取决于其在链中的位置（从N- 末端氨基酸）是Gly，NMeGly，Pro或Pip，或某些类型，其作为上述式中的其余符号在说明书和权利要求书及其盐中定义，具有CXCR4拮抗性质。 这些可以通过基于混合固相和溶液相合成策略的方法制造。

公开(公告)号：US08895695B2

公开(公告)日：2014-11-25

申请号：US12828998

申请日：2010-07-01

申请人： Jürg Zumbrunn ,  Steven J. Demarco ,  Sergio Lociuro ,  Jan Wim Vrijbloed ,  Frank Gombert ,  Reshmi Mukherjee ,  Kerstin Moehle ,  Daniel Obrecht ,  John Anthony Robinson ,  Heiko Henze ,  Barbara Romagnoli ,  Christian Ludin

发明人： Jürg Zumbrunn ,  Steven J. Demarco ,  Sergio Lociuro ,  Jan Wim Vrijbloed ,  Frank Gombert ,  Reshmi Mukherjee ,  Kerstin Moehle ,  Daniel Obrecht ,  John Anthony Robinson ,  Heiko Henze ,  Barbara Romagnoli ,  Christian Ludin

IPC分类号： C07K7/08 ,  C07K7/50

CPC分类号： C07K7/64 ,  A61K38/00 ,  C07K1/047 ,  C07K7/08

摘要： Template-fixed β-hairpin peptidomimetics of the general formula (I) wherein Z is a template-fixed chain of 12, 14 or 18 α-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid), are Gly, NMeGly, Pro or Pip, or of certain types which, as the remaining symbols in the above formula, are defined in the description and the claims, and salts thereof, have CXCR4 antagonizing properties. These β-hairpin peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

摘要翻译： 通式（I）的模板固定和半乳糖肽模拟物，其中Z是12,14或18个α-氨基酸残基的模板固定链，其取决于其在链中的位置（从N- 末端氨基酸）是Gly，NMeGly，Pro或Pip，或某些类型，其作为上述式中的其余符号在说明书和权利要求书及其盐中定义，具有CXCR4拮抗性质。 这些可以通过基于混合固相和溶液相合成策略的方法制造。

公开(公告)号：US07838496B2

公开(公告)日：2010-11-23

申请号：US10550778

申请日：2003-05-02

申请人： Jürg Zumbrunn ,  Steven J. Demarco ,  Sergio Lociuro ,  Jan Wim Vrijbloed ,  Frank Gombert ,  Reshmi Mukherjee ,  Kerstin Moehle ,  Daniel Obrecht ,  Barbara Romagnoli ,  John Anthony Robinson

发明人： Jürg Zumbrunn ,  Steven J. Demarco ,  Sergio Lociuro ,  Jan Wim Vrijbloed ,  Frank Gombert ,  Reshmi Mukherjee ,  Kerstin Moehle ,  Daniel Obrecht ,  Barbara Romagnoli ,  John Anthony Robinson

IPC分类号： A61K38/10 ,  C07K7/06 ,  C07K7/08

CPC分类号： C07K7/06 ,  C07K7/08 ,  C07K14/001

摘要： Template-fixed β-hairpin peptidomimetics of the General Formula (I); wherein Z1 and Z2 are template-fixed chains of 4 and 6 or 5 and 7 α-amino acid residues and salts thereof. They have CXCR4-antagonizing properties and can be used as medicaments. These β-sheet peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

摘要翻译： 通式（I）的模板固定和模板肽模拟物; 其中Z1和Z2是4和6或5和7个α-氨基酸残基及其盐的模板固定链。 它们具有CXCR4拮抗特性，可用作药物。 这些胶体蛋白模拟物可以通过基于混合固相和溶液相合成策略的方法来制造。