公开(公告)号：EP2644618A1

公开(公告)日：2013-10-02

申请号：EP12195556.1

申请日：2008-02-08

申请人： Tranzyme Pharma, Inc.

发明人： Hoveyda, Hamid ,  Fraser, Graeme ,  Beauchemin, Sophie ,  Brassard, Martin ,  Drutz, David ,  Marsault, Eric ,  Quellet, Luc ,  Peterson, Mark L ,  Wang, Zhigang ,  Benkali, Kamel

IPC分类号： C07K5/12 ,  C07D213/65 ,  C07D307/80 ,  C07D491/04 ,  C07D311/02 ,  C07C271/12 ,  C07C211/27 ,  C07C403/18

CPC分类号： A61K31/395 ,  C07C215/42 ,  C07C215/54 ,  C07C271/16 ,  C07C2601/14 ,  C07D273/00 ,  C07D413/06 ,  C07D498/04 ,  C07D498/16

摘要： The present invention relates to intermediates of conformationally-defined macrocyclic compounds that bind to and/or are functional modulators of the ghrelin (growth hormone secretagogue) receptor including GHS-R1a and subtypes, isoforms and/or variants thereof and the use of these interemdaites to prepare said macrocyclic compounds.

摘要翻译： 本发明涉及构象定义的大环化合物的中间体，其与生长素释放肽（生长激素促分泌素）受体（包括GHS-R1a及其亚型，同种型和/或变体）结合和/或是功能性调节剂，以及这些结合蛋白的使用 制备大环化合物。

公开(公告)号：EP2431380A3

公开(公告)日：2013-07-03

申请号：EP11075225.0

申请日：2007-09-11

申请人： Tranzyme Pharma, Inc.

发明人： Marsault, Eric ,  Fraser, Graeme ,  Benakli, Kamel ,  St-Louis, Carl ,  Rouillard, Alain ,  Thomas, Helmut

IPC分类号： C07K5/087 ,  A61P1/00 ,  C07C271/16 ,  C07D213/64 ,  C07D213/65

CPC分类号： C07K5/0812 ,  A61K38/00 ,  C07C271/16 ,  C07D273/00 ,  C07D413/06 ,  C07D417/12 ,  Y02P20/582

摘要： The present invention provides conformationally-defined macrocyclic compounds that bind to and/or are functional modulators of the motilin receptor including subtypes, isoforms and/or variants thereof. These macrocyclic compounds, at a minimum, possess adequate pharmacological properties to be useful as therapeutics for a range of disease indications. In particular, these compounds are useful for treatment and prevention of disorders characterized by hypermotilinemia and/or gastrointestinal hypermotility, including, but not limited to, diarrhea, cancer treatment-related diarrhea, cancer-induced diarrhea, chemotherapy-induced diarrhea, radiation enteritis, radiation-induced diarrhea, stress-induced diarrhea, chronic diarrhea, AIDS-related diarrhea, C. difficile associated diarrhea, traveller's diarrhea, diarrhea induced by graph versus host disease, other types of diarrhea, dyspepsia, irritable bowel syndrome, chemotherapy-induced nausea and vomiting (emesis) and post-operative nausea and vomiting and functional gastrointestinal disorders. In addition, the compounds possess utility for the treatment of diseases and disorders characterized by poor stomach or intestinal absorption, such as short bowel syndrome, celiac disease and cachexia. The compounds also have use for the treatment of inflammatory diseases and disorders of the gastrointestinal tract, such as inflammatory bowel disease, ulcerative colitis, Crohn's disease and pancreatitis. Accordingly, methods of treating such disorders and pharmaceutical compositions including compounds of the present invention are also provided.

公开(公告)号：EP2457925A1

公开(公告)日：2012-05-30

申请号：EP11009051.1

申请日：2005-06-13

申请人： Tranzyme Pharma, Inc.

发明人： Hoveyda, Hamid ,  Peterson, Mark L. ,  Fraser, Graeme ,  Ramaseshan, Mahesh

IPC分类号： C07K5/087 ,  C07K5/12

CPC分类号： C07K5/0827 ,  A61K38/00 ,  C07D273/00 ,  C07D498/08 ,  C07K5/0808 ,  C07K5/0812

摘要： The present invention provides novel conformationally-defined macrocyclic compounds that have been demonstrated to be selective modulators of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R1a and subtypes, isoforms and variants thereof). Methods of synthesizing the novel compounds are also described herein. These compounds are useful as agonists of the ghrelin receptor and as medicaments for treatment and prevention of a range of medical conditions including, but not limited to, metabolic and/or endocrine disorders, gastrointestinal disorders, cardiovascular disorders, obesity and obesity-associated disorders, central nervous system disorders, genetic disorders, hyperproliferative disorders and inflammatory disorders.

摘要翻译： 本发明提供已被证明是生长素释放肽受体（生长激素促分泌素受体，GHS-R1a和亚型，同种型及其变体）的选择性调节剂的新型构象定义的大环化合物。 本文还描述了合成新化合物的方法。 这些化合物可用作生长素释放肽受体的激动剂，并用作治疗和预防一系列医学病症的药物，包括但不限于代谢和/或内分泌疾病，胃肠道疾病，心血管疾病，肥胖症和肥胖相关疾病， 中枢神经系统疾病，遗传疾病，过度增殖性疾病和炎症性疾病。

公开(公告)号：EP2431380A2

公开(公告)日：2012-03-21

申请号：EP11075225.0

申请日：2007-09-11

申请人： Tranzyme Pharma, Inc.

发明人： Marsault, Eric ,  Fraser, Graeme ,  Benakli, Kamel ,  St-Louis, Carl ,  Rouillard, Alain ,  Thomas, Helmut

IPC分类号： C07K5/08 ,  A61P1/00 ,  C07C271/16 ,  C07D213/64 ,  C07D213/65

CPC分类号： C07K5/0812 ,  A61K38/00 ,  C07C271/16 ,  C07D273/00 ,  C07D413/06 ,  C07D417/12 ,  Y02P20/582

摘要： The present invention provides conformationally-defined macrocyclic compounds that bind to and/or are functional modulators of the motilin receptor including subtypes, isoforms and/or variants thereof. These macrocyclic compounds, at a minimum, possess adequate pharmacological properties to be useful as therapeutics for a range of disease indications. In particular, these compounds are useful for treatment and prevention of disorders characterized by hypermotilinemia and/or gastrointestinal hypermotility, including, but not limited to, diarrhea, cancer treatment-related diarrhea, cancer-induced diarrhea, chemotherapy-induced diarrhea, radiation enteritis, radiation-induced diarrhea, stress-induced diarrhea, chronic diarrhea, AIDS-related diarrhea, C. difficile associated diarrhea, traveller's diarrhea, diarrhea induced by graph versus host disease, other types of diarrhea, dyspepsia, irritable bowel syndrome, chemotherapy-induced nausea and vomiting (emesis) and post-operative nausea and vomiting and functional gastrointestinal disorders. In addition, the compounds possess utility for the treatment of diseases and disorders characterized by poor stomach or intestinal absorption, such as short bowel syndrome, celiac disease and cachexia. The compounds also have use for the treatment of inflammatory diseases and disorders of the gastrointestinal tract, such as inflammatory bowel disease, ulcerative colitis, Crohn's disease and pancreatitis. Accordingly, methods of treating such disorders and pharmaceutical compositions including compounds of the present invention are also provided.

摘要翻译： 本发明提供了构象定义的大环化合物，其与胃动素受体结合和/或是功能性调节剂，包括亚型，同种型和/或其变体。 这些大环化合物至少具有足够的药理学性质，可用作一系列疾病适应症的治疗剂。 特别地，这些化合物可用于治疗和预防以高肌钙蛋白血症和/或胃肠动力学特征为特征的疾病，包括但不限于腹泻，癌症治疗相关性腹泻，癌症引起的腹泻，化学疗法诱发的腹泻，放射性肠炎， 辐射诱发的腹泻，应激性腹泻，慢性腹泻，艾滋病相关性腹泻，艰难梭菌相关性腹泻，旅行者腹泻，图形与宿主病引起的腹泻，其他类型的腹泻，消化不良，肠易激综合征，化疗诱发的恶心 和呕吐（呕吐）和术后恶心呕吐和功能性胃肠道疾病。 此外，这些化合物具有治疗以肠胃吸收不良为特征的疾病和病症的用途，例如肠胃综合征，乳糜泻和恶病质。 所述化合物还可用于治疗炎性疾病和胃肠道疾病，例如炎性肠病，溃疡性结肠炎，克罗恩病和胰腺炎。 因此，还提供了治疗这些病症的方法和包括本发明化合物的药物组合物。

公开(公告)号：EP2457893A1

公开(公告)日：2012-05-30

申请号：EP11009050.3

申请日：2005-06-13

申请人： Tranzyme Pharma, Inc.

发明人： Hoveda, Hamid ,  Peterson, Mark L. ,  Fraser, Graeme ,  Ramaseshan, Mahesh

IPC分类号： C07C271/16 ,  C07C271/20 ,  C07D213/64

CPC分类号： C07K5/0827 ,  A61K38/00 ,  C07D273/00 ,  C07D498/08 ,  C07K5/0808 ,  C07K5/0812

摘要： The present invention provides novel conformationally-defined macrocyclic compounds that have been demonstrated to be selective modulators of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R1a and subtypes, isoforms and variants thereof). Methods of synthesizing the novel compounds are also described herein. These compounds are useful as agonists of the ghrelin receptor and as medicaments for treatment and prevention of a range of medical conditions including, but not limited to, metabolic and/or endocrine disorders, gastrointestinal disorders, cardiovascular disorders, obesity and obesity-associated disorders, central nervous system disorders, genetic disorders, hyperproliferative disorders and inflammatory disorders.

摘要翻译： 本发明提供已被证明是生长素释放肽受体（生长激素促分泌素受体，GHS-R1a和亚型，同种型及其变体）的选择性调节剂的新型构象定义的大环化合物。 本文还描述了合成新化合物的方法。 这些化合物可用作生长素释放肽受体的激动剂，并用作治疗和预防一系列医学病症的药物，包括但不限于代谢和/或内分泌疾病，胃肠道疾病，心血管疾病，肥胖症和肥胖相关疾病， 中枢神经系统疾病，遗传疾病，过度增殖性疾病和炎症性疾病。