公开(公告)号：US20120135942A1

公开(公告)日：2012-05-31

申请号：US13319052

申请日：2009-05-07

申请人： Daniel Obrecht ,  Frank Otto Gombert ,  Alexander Lederer ,  Barbara Romagnoli ,  Christian Bisang

发明人： Daniel Obrecht ,  Frank Otto Gombert ,  Alexander Lederer ,  Barbara Romagnoli ,  Christian Bisang

IPC分类号： A61K38/12 ,  C07K7/54 ,  A61P35/00 ,  C07K1/06 ,  A61P31/18 ,  A61P37/00 ,  A61P37/04 ,  A61P7/00 ,  C07K7/64 ,  A61P29/00

CPC分类号： C07K7/08 ,  C07K1/061 ,  C07K7/02

摘要： β-Hairpin peptidomimetics of the general formula Cyclo(-Xaa1-Xaa2-Xaa3-Cys4-Xaa5-Xaa6-Xaa7-Xaa8-Arg9-Tyr10-Cys11-Xaa12-Xaa13-Xaa14-Xaa15-Xaa16-), disulfide bond between Cys4 and Cys11, and pharmaceutically acceptable salts thereof, with Xaa1, Xaa2, Xaa3, Xaa5, Xaa6, Xaa7, Xaa8, Xaa12, Xaa13, Xaa14, Xaa15 and Xaa16 being amino acid residues of certain types which are defined in the description and the claims, 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 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 peptides can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

摘要翻译： 通式为（Xaa1-Xaa2-Xaa3-Cys4-Xaa5-Xaa6-Xaa7-Xaa8-Arg9-Tyr10-Cys11-Xaa12-Xaa13-Xaa14-Xaa15-Xaa16-）的通式肽模拟物，Cys4之间的二硫键 和Cys11及其药学上可接受的盐与在说明书和权利要求书中定义的某些类型的氨基酸残基的Xaa1，Xaa2，Xaa3，Xaa5，Xaa6，Xaa7，Xaa8，Xaa12，Xaa13，Xaa14，Xaa15和Xaa16， 具有CXCR4拮抗特性，可用于预防健康个体中的HIV感染，或用于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：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：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。