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1. 发明申请

WO2012006474A3 COMPOUNDS AND METHODS FOR INHIBITING PHOSPHATE TRANSPORT 审中-公开
标题翻译：抑制磷酸盐运输的化合物和方法
公开(公告)号：WO2012006474A3
公开(公告)日：2013-08-01
申请号：PCT/US2011043262
申请日：2011-07-07
申请人： ARDELYX INC , LEWIS JASON G , JACOBS JEFFREY W , REICH NICHOLAS , LEADBETTER MICHAEL R , BELL NOAH , CHANG HAN-TING , CHEN TAO , NAVRE MARC , CHARMOT DOMINIQUE , CARRERAS CHRISTOPHER , LABONTE ERIC
发明人： LEWIS JASON G , JACOBS JEFFREY W , REICH NICHOLAS , LEADBETTER MICHAEL R , BELL NOAH , CHANG HAN-TING , CHEN TAO , NAVRE MARC , CHARMOT DOMINIQUE , CARRERAS CHRISTOPHER , LABONTE ERIC
IPC分类号： C07D403/02 , A61K31/4965 , A61K31/506 , C07D211/68 , C07D401/00 , C07D403/00 , C07D413/00
CPC分类号： A61K31/5377 , A61K31/497 , A61K31/506 , A61K31/59 , A61K45/06 , C07D239/42 , C07D241/20
摘要： Compounds having activity as phosphate transport inhibitors, more specifically, inhibitors of intestinal apical membrane Na/phosphate co-transport, are disclosed. The compounds have the following structure (I): including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein X, Y and A are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.
摘要翻译：具有作为磷酸盐转运抑制剂的活性的化合物，更具体地，公开了肠顶膜Na /磷酸盐共转运的抑制剂。该化合物具有以下结构（I）：包括立体异构体，其药学上可接受的盐和前药，其中X，Y和A如本文所定义。还公开了与这种化合物的制备和使用相关的方法以及包含这些化合物的药物组合物。

2. 发明申请

WO2012054110A2 COMPOUNDS AND METHODS FOR INHIBITING PHOSPHATE TRANSPORT 审中-公开
标题翻译：抑制磷酸盐运输的化合物和方法
公开(公告)号：WO2012054110A2
公开(公告)日：2012-04-26
申请号：PCT/US2011043267
申请日：2011-07-07
申请人： ARDELYX INC , LEWIS JASON G , JACOBS JEFFREY W , REICH NICHOLAS , LEADBETTER MICHAEL R , BELL NOAH , CHANG HAN-TING , CHEN TAO , NAVRE MARC , CHARMOT DOMINIQUE , CARRERAS CHRISTOPHER , LABONTE ERIC
发明人： LEWIS JASON G , JACOBS JEFFREY W , REICH NICHOLAS , LEADBETTER MICHAEL R , BELL NOAH , CHANG HAN-TING , CHEN TAO , NAVRE MARC , CHARMOT DOMINIQUE , CARRERAS CHRISTOPHER , LABONTE ERIC
IPC分类号： A61K31/506
CPC分类号： C07D213/81 , A61K31/44 , A61K31/4418 , A61K31/4545 , A61K31/496 , A61K31/506 , A61K31/5377 , A61K31/541 , A61K31/551 , A61K31/59 , A61K31/593 , A61K31/785 , A61K45/06 , C07D213/30 , C07D213/38 , C07D213/50 , C07D213/82 , C07D239/34 , C07D239/42 , C07D401/06 , C07D401/10 , C07D401/12 , C07D401/14 , C07D403/12 , C07D405/12 , C07D405/14 , C07D417/12 , C07D417/14
摘要： Compounds having activity as phosphate transport inhibitors, more specifically, inhibitors of intestinal apical membrane Na/phosphate co-transport, are disclosed. The compounds have the following structure (I): (I) including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein X, Y, A, R1 and R2 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.
摘要翻译：具有作为磷酸盐转运抑制剂的活性的化合物，更具体地，公开了肠顶膜Na /磷酸盐共转运的抑制剂。所述化合物具有以下结构（I）：（I），其包括立体异构体，其药学上可接受的盐和前药，其中X，Y，A，R 1和R 2如本文所定义。还公开了与这种化合物的制备和使用相关的方法以及包含这些化合物的药物组合物。

3. 发明申请

WO2010078449A3 COMPOUNDS AND METHODS FOR INHIBITING NHE-MEDIATED ANTIPORT IN THE TREATMENT OF DISORDERS ASSOCIATED WITH FLUID RETENTION OR SALT OVERLOAD AND GASTROINTESTINAL TRACT DISORDERS 审中-公开
标题翻译：抑制NHE介导的抗生素治疗与流体滞留，盐负荷过重和胃肠道病变相关的疾病的化合物和方法
公开(公告)号：WO2010078449A3
公开(公告)日：2010-09-30
申请号：PCT/US2009069852
申请日：2009-12-30
申请人： ARDELYX INC , CHARMOT DOMINIQUE , JACOBS JEFFREY W , LEADBETTER MICHAEL ROBERT , NAVRE MARC , CARRERAS CHRIS , BELL NOAH
发明人： CHARMOT DOMINIQUE , JACOBS JEFFREY W , LEADBETTER MICHAEL ROBERT , NAVRE MARC , CARRERAS CHRIS , BELL NOAH
IPC分类号： C07C311/29 , A61K31/18 , A61K31/472 , A61K31/4725 , A61K31/517 , A61K31/662 , A61K31/675 , A61K45/06 , C07D217/04 , C07D401/12 , C07F9/38 , C07F9/40 , C07F9/572 , C07F9/62
CPC分类号： A61K31/4725 , A61K31/18 , A61K31/472 , A61K31/517 , A61K31/662 , A61K31/675 , A61K45/06 , C07C311/29 , C07D215/14 , C07D217/04 , C07D217/14 , C07D217/16 , C07D401/12 , C07F9/3808 , C07F9/3834 , C07F9/3882 , C07F9/5765 , C07F9/60 , C07F9/65583
摘要： The present disclosure is directed to compounds and methods for the treatment of disorders associated with fluid retention or salt overload, such as heart failure (in particular, congestive heart failure), chronic kidney disease, end-stage renal disease, liver disease, and peroxisome proliferator-activated receptor (PPAR) gamma agonist-induced fluid retention. The present disclosure is also directed to compounds and methods for the treatment of hypertension. The present disclosure is also directed to compounds and methods for the treatment of gastrointestinal tract disorders, including the treatment or reduction of pain associated with gastrointestinal tract disorders. The methods generally comprise administering to a mammal in need thereof a pharmaceutically effective amount of a compound, or a pharmaceutical composition comprising such a compound, that is designed to be substantially active in the gastrointestinal (GI) tract to inhibit NHE-mediated antiport of sodium ions and hydrogen ions therein. More particularly, the method comprises administering to a mammal in need thereof a pharmaceutically effective amount of a compound, or a pharmaceutical composition comprising such a compound, that inhibits NHE-3, -2 and/or -8 mediated antiport of sodium and/or hydrogen ions in the GI tract and is designed to be substantially impermeable to the layer of epithelial cells, or more specifically the epithelium of the GI tract. As a result of the compound being substantially impermeable, it is not absorbed and is thus essentially systemically non-bioavailable, so as to limit the exposure of other internal organs (e.g., liver, heart, brain, etc.) thereto. The present disclosure is still further directed to a method wherein a mammal is administered such a compound with a fluid-absorbing polymer, such that the combination acts as described above and further provides the ability to sequester fluid and/or salt present in the GI tract.
摘要翻译：本公开涉及用于治疗与体液潴留或盐超负荷相关的病症例如心力衰竭（特别是充血性心力衰竭），慢性肾病，终末期肾病，肝病和过氧化物酶体的化合物和方法增殖激活受体（PPAR）γ激动剂诱导的液体潴留。本公开还涉及用于治疗高血压的化合物和方法。本公开还涉及用于治疗胃肠道病症的化合物和方法，包括治疗或减轻与胃肠道病症相关的疼痛。所述方法通常包括向需要其的哺乳动物施用药物有效量的化合物或包含该化合物的药物组合物，其被设计为在胃肠（GI）道中基本上具有活性以抑制NHE介导的钠离子和氢离子。更特别地，所述方法包括向需要其的哺乳动物施用药学有效量的化合物或包含该化合物的药物组合物，其抑制NHE-3，-2和/或-8介导的钠和/或氢气离子在胃肠道中，并被设计为对上皮细胞层，或更具体而言，胃肠道的上皮层基本上不可渗透。由于该化合物基本上不可渗透，所以它不被吸收，因此基本上不具有生物可利用性，从而限制其它内部器官（例如肝脏，心脏，脑等）暴露于其中。本发明还进一步涉及一种方法，其中将哺乳动物与流体吸收聚合物一起给予这种化合物，使得所述组合如上所述起作用并进一步提供螯合存在于胃肠道中的流体和/或盐的能力。

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