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：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。