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：US20130150299A1

公开(公告)日：2013-06-13

申请号：US13764099

申请日：2013-02-11

申请人： Daniel OBRECHT ,  Frank Gombert ,  Steven J. Demarco ,  Christian Ludin ,  Jan Wim Vrijbloed ,  Kerstin Moehle ,  John-Anthony Robinson ,  Reshmi Mukherjee ,  Heiko Henze ,  Barbara Romagnoli

发明人： Daniel OBRECHT ,  Frank Gombert ,  Steven J. Demarco ,  Christian Ludin ,  Jan Wim Vrijbloed ,  Kerstin Moehle ,  John-Anthony Robinson ,  Reshmi Mukherjee ,  Heiko Henze ,  Barbara Romagnoli

IPC分类号： A61K38/12

CPC分类号： C07K7/56 ,  A61K38/00 ,  A61K38/12 ,  C07K7/64

摘要： The template-fixed β-hairpin peptidomimetics Cyclo(-Tyr-His-X-Cys-Ser-Ala-DPro-Dab-Arg-Tyr-Cys-Tyr-Gln-Lys-DPro-Pro), disulfide bond between Cys4 and Gys11, and pharmaceutically acceptable salts thereof, with X being Ala or Tyr, 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, in particular, for stem cell mobilisation of peripheral blood stem cells and/or mesenchymal stem cell (MSC) and/or other stem cells which retention depend on the CXCR4-receptor. These β-hairpin peptidomimetics can be manufactured by a process which is based on a mixed solid- and Solution phase synthetic strategy, using methods which are well known to those adequately skilled in peptide chemistry.

摘要翻译： 模板固定的β-发夹肽模拟物Cyclo（-Tyr-His-X-Cys-Ser-Ala-DPro-Dab-Arg-Tyr-Cys-Tyr-Gln-Lys-DPro-Pro），Cys4和Gys11之间的二硫键 和其药学上可接受的盐，其中X为Ala或Tyr，具有CXCR4拮抗性质，可用于预防健康个体的HIV感染或减缓和停止感染患者的病毒进展; 或其中癌症介导或由CXCR4受体活性产生; 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; 或特别是用于干细胞移动外周血干细胞和/或间充质干细胞（MSC）和/或其它干细胞，其保留取决于CXCR4-受体。 这些β-发夹肽模拟物可以通过使用基于混合固相和溶液相合成策略的方法来制备，该方法使用肽化学中相当熟练技术人员众所周知的方法。

公开(公告)号：US08399611B2

公开(公告)日：2013-03-19

申请号：US12528926

申请日：2007-02-28

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

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

IPC分类号： A61K38/12 ,  A61K38/10 ,  A61K38/04

CPC分类号： C07K7/56 ,  A61K38/00 ,  A61K38/12 ,  C07K7/64

摘要： The template-fixed β-hairpin peptidomimetics Cyclo(-Tyr-His-X-Cys-Ser-Ala-DPro-Dab-Arg-Tyr-Cys-Tyr-Gln-Lys-DPro-Pro), disulfide bond between Cys4 and Cys11, and pharmaceutically acceptable salts thereof, with X being Ala or Tyr, 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 for treating inflammation, or, in particular, for stem cell mobilization of peripheral blood stem cells and/or mesenchymal stem cell (MSC) and/or other stem cells which retention depend on the CXCR4-receptor.

摘要翻译： 模板固定和固定肽模拟物Cyclo（-Tyr-His-X-Cys-Ser-Ala-DPro-Dab-Arg-Tyr-Cys-Tyr-Gln-Lys-DPro-Pro），Cys4和 Cys11及其药学上可接受的盐，X为Ala或Tyr，具有CXCR4拮抗性质，可用于预防健康个体的HIV感染或减缓和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; 或用于治疗炎症，或特别是用于干细胞移动外周血干细胞和/或间充质干细胞（MSC）和/或其它干细胞，其保留取决于CXCR4受体。

公开(公告)号：US20100048463A1

公开(公告)日：2010-02-25

申请号：US12528926

申请日：2007-02-28

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

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

IPC分类号： C07K7/56 ,  A61K38/12 ,  A61P31/12 ,  A61P31/18

CPC分类号： C07K7/56 ,  A61K38/00 ,  A61K38/12 ,  C07K7/64

摘要： The template-fixed B-hairpin peptidomimetics Cyclo(-Tyr-His-X-Cys-Ser-Ala-DPro-Dab-Arg-Tyr-Cys-Tyr-Gln-Lys-DPro-Pro), disulfide bond between Cys4 and Gys11, and pharmaceutically acceptable salts thereof, with X being Ala or Tyr, 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, in particular, for stem cell mobilisation of peripheral blood stem cells and/or mesenchymal stem cell (MSC) and/or other stem cells which retention depend on the CXCR4-receptor. These β-hairpin peptidomimetics can be manufactured by a process which is based on a mixed solid- and Solution phase synthetic strategy, using methods which are well known to those adequately skilled in peptide chemistry.

摘要翻译： 模板固定的B发夹肽模拟物Cyclo（-Tyr-His-X-Cys-Ser-Ala-DPro-Dab-Arg-Tyr-Cys-Tyr-Gln-Lys-DPro-Pro），Cys4和Gys11之间的二硫键 和其药学上可接受的盐，其中X为Ala或Tyr，具有CXCR4拮抗性质，可用于预防健康个体的HIV感染或减缓和停止感染患者的病毒进展; 或其中癌症介导或由CXCR4受体活性产生; 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; 或特别是用于干细胞移动外周血干细胞和/或间充质干细胞（MSC）和/或其它干细胞，其保留取决于CXCR4-受体。 这些和包装肽模拟物可以通过使用基于混合固相和溶液相合成策略的方法，使用肽化学方面熟练的技术熟知的方法来制造。

公开(公告)号：US20070078079A1

公开(公告)日：2007-04-05

申请号：US10555088

申请日：2004-04-29

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

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

IPC分类号： A61K38/12 ,  C07K5/12

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 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）的模板固定的β-发夹肽模拟物，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-末端开始计数 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拮抗特性，可用于 预防健康人中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β-发夹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备。

公开(公告)号：US08633163B2

公开(公告)日：2014-01-21

申请号：US12524862

申请日：2007-01-29

申请人： Daniel Obrecht ,  Frank Gombert ,  Steve J. Demarco ,  Christian Ludin ,  Alexander Lederer ,  Christian Bisang ,  Odile Sellier-Kessler ,  Francoise Jung ,  Reshmi Mukherjee ,  Heiko Henze ,  Barbara Romagnoli

发明人： Daniel Obrecht ,  Frank Gombert ,  Steve J. Demarco ,  Christian Ludin ,  Alexander Lederer ,  Christian Bisang ,  Odile Sellier-Kessler ,  Francoise Jung ,  Reshmi Mukherjee ,  Heiko Henze ,  Barbara Romagnoli

IPC分类号： A61K38/00 ,  C07K14/72 ,  C07K14/705 ,  A61K38/04 ,  C07K5/00 ,  C07K7/00 ,  C07K16/00 ,  C07K17/00

CPC分类号： C07K7/64 ,  A61K38/00 ,  C07K5/02 ,  C07K5/101 ,  C07K5/1013 ,  C07K5/1016 ,  C07K5/1021 ,  C07K5/1024 ,  C07K7/06 ,  C07K7/08

摘要： Template-fixed β-hairpin peptidomimetics of the general formula (I) wherein Z is a template-fixed chain of 4 α-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid) are Gly, 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 the property to agonize or to antagonize GPCR receptors such as CXCR3, urotensin and CCR10. They can be used as medicaments to treat or prevent diseases such as cardiovascular disorders, dermatological disorders, endocrine system and hormone disorders, metabolic diseases, inflammatory diseases, neurological diseases, respiratory diseases, haematological diseases and cancer. 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）的模板固定的β-发夹肽模拟物，其中Z是4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-末端氨基酸开始计数）为 Gly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及其盐中定义，具有激动或拮抗GPCR受体如CXCR3，尿素调节素和CCR10的性质。 它们可以用作治疗或预防心血管疾病，皮肤病，内分泌系统和激素失调，代谢疾病，炎性疾病，神经疾病，呼吸系统疾病，血液病和癌症等疾病的药物。 这些β-发夹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备。

公开(公告)号：US20100093644A1

公开(公告)日：2010-04-15

申请号：US12524862

申请日：2007-01-29

申请人： Daniel Obrecht ,  Frank Gombert ,  Steve J. Demarco ,  Christian Ludin ,  Alexander Lederer ,  Christian Bisang ,  Odile Sellier-Kessler ,  Francoise Jung ,  Reshmi Mukherjee ,  Heiko Henze ,  Barbara Romagnoli

发明人： Daniel Obrecht ,  Frank Gombert ,  Steve J. Demarco ,  Christian Ludin ,  Alexander Lederer ,  Christian Bisang ,  Odile Sellier-Kessler ,  Francoise Jung ,  Reshmi Mukherjee ,  Heiko Henze ,  Barbara Romagnoli

IPC分类号： A61K38/07 ,  C07K5/10

CPC分类号： C07K7/64 ,  A61K38/00 ,  C07K5/02 ,  C07K5/101 ,  C07K5/1013 ,  C07K5/1016 ,  C07K5/1021 ,  C07K5/1024 ,  C07K7/06 ,  C07K7/08

摘要： Template-fixed β-hairpin peptidomimetics of the general formula (I) wherein Z is a template-fixed chain of 4 α-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid) are Gly, 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 the property to agonize or to antagonize GPCR receptors such as CXCR3, urotensin and CCR10. They can be used as medicaments to treat or prevent diseases such as cardiovascular disorders, dermatological disorders, endocrine system and hormone disorders, metabolic diseases, inflammatory diseases, neurological diseases, respiratory diseases, haematological diseases and cancer. 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4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-末端氨基酸开始计数） 是Gly，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，具有激动或拮抗GPCR受体如CXCR3，尿素调节素和CCR10的性质。 它们可以用作治疗或预防心血管疾病，皮肤病，内分泌系统和激素失调，代谢疾病，炎性疾病，神经疾病，呼吸系统疾病，血液病和癌症等疾病的药物。 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：US08658604B2

公开(公告)日：2014-02-25

申请号：US11816589

申请日：2005-02-17

申请人： Steven J. DeMarco ,  Kerstin Moehle ,  Heiko Henze ,  Odile Sellier ,  Françoise Jung ,  Frank Gombert ,  Daniel Obrecht ,  Christian Ludin

发明人： Steven J. DeMarco ,  Kerstin Moehle ,  Heiko Henze ,  Odile Sellier ,  Françoise Jung ,  Frank Gombert ,  Daniel Obrecht ,  Christian Ludin

IPC分类号： A61K38/10 ,  A61K38/12

CPC分类号： C07K7/06 ,  A61K38/00 ,  C07K1/061 ,  C07K7/08 ,  C07K7/64

摘要： Template-fixed β-hairpin peptidomimetics of the general formulae wherein Z is a chain of 11 α-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid) are Gly, or Pro, or Pro(4NHCOPhe), 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 the property to inhibit proteases, in particular serine proteases, especially Cathepsin G or Elastase or Tryptase. These β-hairpin peptidomimetics can be manufactured by processes which are based on a mixed solid- and solution phase synthetic strategy.

摘要翻译： 具有通式的模板固定的β-发夹肽模拟物，其中Z是11个α-氨基酸残基的链，其取决于其在链中的位置（从N-末端氨基酸开始计数）是Gly或Pro，或 Pro（4NHCOPhe）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，具有抑制蛋白酶，特别是丝氨酸蛋白酶，特别是组织蛋白酶G或弹性蛋白酶 或Tryptase。 这些β-发夹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备。