BRPI0923861B8 - compostos e composições farmacêuticas para inibir o antiporte nhe-mediado no tratamento de distúrbios associados com a retenção de fluido ou com a sobrecarga de sal e distúrbios do trato gastrointestinal - Google Patents

compostos e composições farmacêuticas para inibir o antiporte nhe-mediado no tratamento de distúrbios associados com a retenção de fluido ou com a sobrecarga de sal e distúrbios do trato gastrointestinal

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Publication number
BRPI0923861B8
BRPI0923861B8 BRPI0923861A BRPI0923861A BRPI0923861B8 BR PI0923861 B8 BRPI0923861 B8 BR PI0923861B8 BR PI0923861 A BRPI0923861 A BR PI0923861A BR PI0923861 A BRPI0923861 A BR PI0923861A BR PI0923861 B8 BRPI0923861 B8 BR PI0923861B8
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Brazil
Prior art keywords
gastrointestinal tract
compounds
compound
disorders
methods
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BRPI0923861A
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English (en)
Inventor
Carreras Chris
Charmot Dominique
W Jacobs Jeffrey
Navre Marc
Robert Leadbetter Michael
Bell Noah
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Ardelyx Inc
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Application filed by Ardelyx Inc filed Critical Ardelyx Inc
Publication of BRPI0923861A2 publication Critical patent/BRPI0923861A2/pt
Publication of BRPI0923861B1 publication Critical patent/BRPI0923861B1/pt
Publication of BRPI0923861B8 publication Critical patent/BRPI0923861B8/pt

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    • C07D217/04—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
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    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
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    • C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
    • C07C311/29—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Abstract

compostos e métodos para inibir o antiporte nhe-mediado no tratamento de distúrbios associados com a retenção de fluido ou com a sobrecarga de sal e distúrbios do trato gastrointestinal. a presente invenção é direcionada a compostos e métodos para o tratamento de distúrbios associados com a retenção de fluido ou sobrecarga de sal, tais como a insuficiência cardíaca (em particular, insuficiência cardíaca congestiva), doença renal crônica, doença renal em estágio terminal, doença hepática, e retenção de fluido induzida por agente agonista gama do receptor ativado por proliferador de peroxissomo (ppar). a presente invenção é também direcionada a compostos e métodos para o tratamento da hipertensão. a presente invenção é também direcionada a compostos e métodos para o tratamento de distúrbios do trato gastrointestinal, incluindo o tratamento ou redução da dor associada a distúrbios do trato gastrointestinal. os métodos geralmente compreendem administrar a um mamífero com necessidade disso uma quantidade farmaceuticamente eficaz de um composto, ou de uma composição farmacêutica compreendendo um tal composto, que é desenvolvido para ser substancialmente ativo no trato gastrointestinal (gi) para inibir nele o antiporte nhe-mediado de íons sódio e de íons hidrogênio. mais particularmente, o método compreende administrar a um mamífero com necessidade disso uma quantidade farmaceuticamente eficaz de um composto, ou de uma composição farmacêutica compreendendo tal composto, que inibe o antiporte nhe-3, 2- e/ou -8 -mediado de íons sódio e/ou de íons hidrogênio no trato gastrointestinal e é desenvolvido para ser substancialmente impermeável à camada de células epiteliais, ou mais especificamente ao epitélio do trato gastrointestinal. como um resultado do composto ser substancialmente impermeável, ele não é absorvido e é assim essencialmente sistematicamente não biodisponível, de modo a limitar a exposição dos outros órgãos internos ( por exemplo, fígado, coração, cérebro, etc) a ele. a presente invenção é ainda direcionada a um método em que um mamífero recebe administração de um tal composto com um polímero de absorção de fluido, de modo que a combinação funciona como descrito acima e ainda adicionalmente fornece a capacidade de sequestrar fluido e/ou sal presente no trato gi.
BRPI0923861A 2008-12-31 2009-12-30 compostos e composições farmacêuticas para inibir o antiporte nhe-mediado no tratamento de distúrbios associados com a retenção de fluido ou com a sobrecarga de sal e distúrbios do trato gastrointestinal BRPI0923861B8 (pt)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US14185308P 2008-12-31 2008-12-31
US61/141.853 2008-12-31
US16950909P 2009-04-15 2009-04-15
US61/169.509 2009-04-15
US23784209P 2009-08-28 2009-08-28
US61/237.842 2009-08-28
PCT/US2009/069852 WO2010078449A2 (en) 2008-12-31 2009-12-30 Compounds and methods for inhibiting nhe-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders

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BRPI0923861A2 BRPI0923861A2 (pt) 2015-07-28
BRPI0923861B1 BRPI0923861B1 (pt) 2020-03-10
BRPI0923861B8 true BRPI0923861B8 (pt) 2021-05-25

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018129556A1 (en) * 2017-01-09 2018-07-12 Ardelyx, Inc. Compounds and methods for inhibiting nhe-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders
ES2657938T3 (es) * 2008-12-31 2018-03-07 Ardelyx, Inc. Compuestos y métodos para inhibir el antipuerto mediado por NHE en el tratamiento de trastornos asociados a la retención de líquidos o a la sobrecarga de sales y trastornos del tracto gastrointestinal
US10543207B2 (en) 2008-12-31 2020-01-28 Ardelyx, Inc. Compounds and methods for inhibiting NHE-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders
CN102757390B (zh) * 2011-04-27 2015-04-22 中国中化股份有限公司 一种制备2-甲氧基-4-肼基-5-氟嘧啶的方法
US10376481B2 (en) * 2012-08-21 2019-08-13 Ardelyx, Inc. Compounds and methods for inhibiting NHE-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders
RU2684097C2 (ru) * 2012-08-21 2019-04-04 Эрделикс, Инк. Соединения и способы для ингибирования NHE-опосредованного антипорта в лечении расстройств, ассоциированных с задержкой жидкости или солевой перегрузкой, и заболеваний желудочно-кишечного тракта
CN104902930A (zh) * 2012-08-21 2015-09-09 阿德利克斯公司 在治疗与液体潴留或盐分过载相关的疾病和胃肠道疾病中用于抑制nhe-介导的反向转运的化合物和方法
ES2735992T3 (es) * 2013-04-12 2019-12-23 Ardelyx Inc Compuestos de unión a NHE3 y procedimientos para inhibir el transporte de fosfatos
WO2015003083A1 (en) 2013-07-02 2015-01-08 The California Institute For Biomedical Research Compounds for treatment of cystic fibrosis
WO2015021358A2 (en) * 2013-08-09 2015-02-12 Dominique Charmot Compounds and methods for inhibiting phosphate transport
WO2015084158A1 (en) * 2013-12-06 2015-06-11 N.V. Nutricia A pyrimidine derivative and a fatty acid source for use in the treatment of constipation
LT3173408T (lt) 2014-07-25 2018-12-27 Taisho Pharmaceutical Co., Ltd. Fenilo tetrahidroizochinolino junginys, turintis heteroarilo pakaitų
DE102014019388A1 (de) 2014-12-29 2016-06-30 Susanne Wagner Arzneimittel auf der Basis von Maghämit zur gleichzeitigen Reduzierung der gastrointestinalen Natriumresorption und Phosphatresorption
WO2016112120A1 (en) * 2015-01-07 2016-07-14 The California Institute For Biomedical Research Compounds for treatment of cystic fibrosis
JP6421100B2 (ja) * 2015-09-04 2018-11-07 株式会社ダイセル カルボン酸アミド化合物の製造方法
US10016379B2 (en) * 2015-10-30 2018-07-10 Robin L. Webb Method of treatment for third spacing
CN108778345B (zh) * 2016-02-01 2022-11-29 阿拉基斯医疗公司 治疗rna介导的疾病的化合物和方法
EA201991676A1 (ru) 2017-01-09 2020-01-30 Арделикс, Инк. Ингибиторы nhe-опосредованного антипорта
EP3565808A1 (en) 2017-01-09 2019-11-13 Ardelyx, Inc. Compounds useful for treating gastrointestinal tract disorders
WO2018165520A1 (en) 2017-03-10 2018-09-13 Vps-3, Inc. Metalloenzyme inhibitor compounds
BR112020002322A2 (pt) 2017-08-04 2020-09-01 Ardelyx, Inc. derivados de ácido glicirretinínico para o tratamento de hipercalemia
CA3081564A1 (en) * 2017-11-02 2019-05-09 Ube Industries, Ltd. Double-headed protease inhibitor
WO2019091503A1 (en) 2017-11-13 2019-05-16 Zentiva K.S. Solid forms of tenapanor and method of preparation of tenapanor
CN109897044A (zh) * 2017-12-07 2019-06-18 北京大学 抗神经病理性疼痛化合物及其制备方法
WO2020051014A1 (en) 2018-09-04 2020-03-12 Teva Pharmaceuticals International Gmbh Processes for the preparation of tenapanor and intermediates thereof
CN109321529A (zh) * 2018-10-19 2019-02-12 浙江工商大学 一种体外肠道模型的构建方法和应用
AU2020218255A1 (en) 2019-02-07 2021-09-09 Ardelyx, Inc. Glycyrrhetinic acid derivatives for use in treating hyperkalemia
CN111954669B (zh) * 2019-03-14 2023-04-07 深圳仁泰医药科技有限公司 Nhe3抑制剂的晶型a及其制备方法和应用
ES2927100T3 (es) 2019-05-16 2022-11-02 Lilly Co Eli Compuestos inhibidores del intercambiador de sodio-hidrógeno 3
JP2022533251A (ja) 2019-05-21 2022-07-21 アルデリックス， インコーポレイテッド 患者において血清リン酸塩を低下させるための組み合わせ
CN112679427B (zh) * 2019-10-17 2023-05-12 江苏恒瑞医药股份有限公司 四氢异喹啉类衍生物、其制备方法及其在医药上的应用
CN111217490B (zh) * 2019-12-30 2024-09-06 北京航天环境工程有限公司 一种轻型填料的双层生物滤池系统和应用
CN116322777A (zh) * 2020-08-04 2023-06-23 西吉隆医疗股份有限公司 杂芳基和杂环基化合物
CN112047881B (zh) * 2020-10-10 2023-04-11 山东汇海医药化工有限公司 一种坦帕诺的制备方法
EP4265608A1 (en) * 2020-12-18 2023-10-25 Shanghai Jemincare Pharmaceuticals Co., Ltd. Benzoheterocycle substituted tetrahydroisoquinoline compound
TWI842576B (zh) * 2022-06-20 2024-05-11 大陸商上海濟煜醫藥科技有限公司 苯並雜環取代四氫異喹啉類化合物鹽型及其製備方法

Family Cites Families (130)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3926891A (en) 1974-03-13 1975-12-16 Dow Chemical Co Method for making a crosslinkable aqueous solution which is useful to form soft, water-swellable polyacrylate articles
US3935099A (en) 1974-04-03 1976-01-27 The United States Of America As Represented By The Secretary Of Agriculture Method of reducing water content of emulsions, suspensions, and dispersions with highly absorbent starch-containing polymeric compositions
US3997484A (en) 1974-04-03 1976-12-14 The United States Of America As Represented By The Secretary Of Agriculture Highly-absorbent starch-containing polymeric compositions
US4090013A (en) 1975-03-07 1978-05-16 National Starch And Chemical Corp. Absorbent composition of matter
JPS51125468A (en) 1975-03-27 1976-11-01 Sanyo Chem Ind Ltd Method of preparing resins of high water absorbency
JPS5346389A (en) 1976-10-07 1978-04-25 Kao Corp Preparation of self-crosslinking polymer of acrylic alkali metal salt
US4190562A (en) 1977-04-04 1980-02-26 The B. F. Goodrich Company Improved water absorbent copolymers of copolymerizable carboxylic acids and acrylic or methacrylic esters
US4470975A (en) 1977-10-21 1984-09-11 The Johns Hopkins University Method and composition for the elimination of water from an animal body
US4286082A (en) 1979-04-06 1981-08-25 Nippon Shokubai Kagaku Kogyo & Co., Ltd. Absorbent resin composition and process for producing same
JPS6025045B2 (ja) 1980-03-19 1985-06-15 製鉄化学工業株式会社 塩水吸収能のすぐれたアクリル酸重合体の製造方法
JPS57158209A (en) 1981-03-25 1982-09-30 Kao Corp Production of bead-form highly water-absorbing polymer
JPS5832607A (ja) 1981-08-20 1983-02-25 Kao Corp 吸水性に優れた吸水材料の製造法
US4985518A (en) 1981-10-26 1991-01-15 American Colloid Company Process for preparing water-absorbing resins
JPS6187702A (ja) 1984-10-05 1986-05-06 Seitetsu Kagaku Co Ltd 吸水性樹脂の製造方法
US4708997A (en) 1985-07-22 1987-11-24 The Dow Chemical Company Suspending agent for the suspension polymerization of water-soluble monomers
US4806532A (en) 1985-10-08 1989-02-21 Mayo Foundation For Medical Education And Research Inhibition of epithelial phosphate transport
DE3544770A1 (de) 1985-12-18 1987-06-19 Stockhausen Chem Fab Gmbh Verfahren und vorrichtung zum kontinuierlichen herstellen von polymerisaten und copolymerisaten der acrylsaeure und/oder methacrylsaeure
US4766004A (en) 1986-12-19 1988-08-23 Warner-Lambert Company Crunchy, highly palatable, bulk-increasing, dietary fiber supplement composition
IT1217123B (it) 1987-02-05 1990-03-14 Rotta Research Lab Derivati otticamente attivi dell acido 5 pentilammino 5 oxo pentanoico r ad attivita antagonista della colecistochinina e procedimento per la loro preparazione
US4999200A (en) 1987-12-09 1991-03-12 Marion Laboratories Psyllium tablet composition, method of manufacture and method of use
US5149541A (en) 1988-10-03 1992-09-22 The Procter & Gamble Company Psyllium-containing produces with a distribution of particle size
US5145906A (en) 1989-09-28 1992-09-08 Hoechst Celanese Corporation Super-absorbent polymer having improved absorbency properties
US5126150A (en) 1990-10-01 1992-06-30 The Procter & Gamble Company Compositions containing psyllium
HUT64023A (en) 1991-03-22 1993-11-29 Sandoz Ag Process for producing aminoguanidine derivatives and pharmaceutical compositions comprising such compounds
FR2674849B1 (fr) 1991-04-02 1994-12-23 Logeais Labor Jacques Nouveaux derives de n-cyclohexyl benzamides ou thiobenzamides, leurs preparations et leurs applications en therapeutique.
US5140102A (en) 1991-09-23 1992-08-18 Monsanto Company Pentadecapeptide, guanylin, which stimulates intestinal guanylate cyclase
US5824645A (en) 1991-12-30 1998-10-20 Neurex Corporation Method of treating inflammation
SG50624A1 (en) 1991-12-30 1998-07-20 Neurex Corp Methods of producing analgesia and enhancing opiate analgesia
US5969097A (en) 1992-06-23 1999-10-19 G. D. Searle & Co. Human guanylin
ES2107698T3 (es) 1993-02-20 1997-12-01 Hoechst Ag Benzoilguanidinas sustituidas, procedimiento para su preparacion, su utilizacion como medicamento, como inhibidores del intercambio celular de na+/h+ o como agente de diagnostico, asi como medicamento que las contiene.
MX213505B (pt) 1993-02-24 2003-04-03
US5629377A (en) 1993-03-10 1997-05-13 The Dow Chemical Company Water absorbent resin particles of crosslinked carboxyl containing polymers and method of preparation
IL109570A0 (en) 1993-05-17 1994-08-26 Fujisawa Pharmaceutical Co Guanidine derivatives, pharmaceutical compositions containing the same and processes for the preparation thereof
US5489670A (en) 1993-10-29 1996-02-06 G. D. Searle & Co. Human uroguanylin
US5610145A (en) 1994-04-15 1997-03-11 Warner-Lambert Company Tachykinin antagonists
US5650222A (en) 1995-01-10 1997-07-22 The Procter & Gamble Company Absorbent foam materials for aqueous fluids made from high internal phase emulsions having very high water-to-oil ratios
DE19518796A1 (de) 1995-05-22 1996-11-28 Hoechst Ag Fluorphenylsubstituierte Alkenylcarbonsäure-guanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament
US6054429A (en) 1996-03-08 2000-04-25 Elan Pharmaceuticals, Inc. Epidural method of producing analgesia
EP1336409B1 (en) 1995-06-27 2007-04-11 Eisai R&D Management Co., Ltd. Compositions and formulations for producing analgesia and for inhibiting progression of neuropathic pain disorders
US5795864A (en) 1995-06-27 1998-08-18 Neurex Corporation Stable omega conopetide formulations
US5550167A (en) 1995-08-30 1996-08-27 The Procter & Gamble Company Absorbent foams made from high internal phase emulsions useful for acquiring aqueous fluids
TR199800924T2 (xx) 1995-11-24 1998-08-21 Smithkline Beecham S.P.A. Quinoline t�revleri.
GB9524104D0 (en) 1995-11-24 1996-01-24 Smithkline Beecham Spa Novel compounds
DE19548812A1 (de) 1995-12-27 1997-07-03 Hoechst Ag Verwendung von Inhibitoren des zellulären Na·+·/H·+·-Exchangers (NHE) zur Herstellung eines Medikaments zur Atemstimulation
EP0837055A1 (en) 1996-07-30 1998-04-22 Hoechst Aktiengesellschaft Substituted Indanylidineacetylguanidines, process for their preparation, their use as medicaments or diagnostic and medicaments containing them
DE19633966A1 (de) 1996-08-22 1998-02-26 Hoechst Ag Phenylsubstituierte Alkenylcarbonsäure-guanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament
WO1998011090A2 (en) 1996-09-16 1998-03-19 Warner-Lambert Company 3-alkyl-3-phenyl-piperidines
PT975347E (pt) 1997-02-28 2008-05-23 Nycomed Gmbh Combinação sinérgica de inibidores da pde e agonistas da adenilato ciclase ou agonistas da guanil ciclise
NZ329807A (en) 1997-04-23 2000-07-28 Pfizer NK-1 receptor antagonists and P receptor antagonists 2-Diarylmethyl-3-amino-1-azabicyclo[2.2.2]octane derivatives and amino substituted N-containing rings as agents for treating irritable bowel syndrome
KR100219918B1 (ko) 1997-07-03 1999-09-01 김윤 대장선택적 약물전달용 조성물
US20010006972A1 (en) 1998-04-21 2001-07-05 Stephen A. Williams Nk-1 receptor antagonists for the treatment of symptoms of irritable bowel syndrome
KR20000011247A (ko) 1998-07-23 2000-02-25 김윤 다당류를이용한대장선택성약물전달조성물및약학제제
DE19849722A1 (de) 1998-10-28 2000-05-04 Aventis Pharma Gmbh Substituierte Phenyl-alkenoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament
EP1175425A2 (en) 1999-01-21 2002-01-30 The Board Of Regents, The University Of Texas System Inhibitors of intestinal apical membrane na/phosphate co-transportation
US6624150B2 (en) 1999-02-26 2003-09-23 Inspire Pharmaceuticals, Inc. Method of treating gastrointestinal tract disease with purinergic receptor agonists
US6287609B1 (en) 1999-06-09 2001-09-11 Wisconsin Alumni Research Foundation Unfermented gel fraction from psyllium seed husks
US6475509B1 (en) 1999-07-19 2002-11-05 The University Of North Carolina At Chapel Hill Covalent conjugates of sodium channel blockers and active compounds
AR030911A1 (es) 1999-07-20 2003-09-03 Smithkline Beecham Corp Uso de n-aril-2-sulfonamidobenzamidas para la manufactura de un medicamento para el tratamiento de la insuficiencia renal cronica y composiciones farmaceuticas
US6107356A (en) 1999-08-23 2000-08-22 The Procter & Gamble Company High suction polymeric foam materials
DE19941764A1 (de) * 1999-09-02 2001-03-15 Aventis Pharma Gmbh Substituierte Acylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikamente oder Diagnostika sowie sie enthaltende Medikamente
SE9903291D0 (sv) 1999-09-15 1999-09-15 Astra Ab New process
DE19945302A1 (de) 1999-09-22 2001-03-29 Merck Patent Gmbh Biphenylderivate als NHE-3-Inhibitoren
US6887870B1 (en) 1999-10-12 2005-05-03 Bristol-Myers Squibb Company Heterocyclic sodium/proton exchange inhibitors and method
WO2001032180A2 (en) 1999-11-01 2001-05-10 Rodeva Limited Composition for treatment of constipation and irritable bowel syndrome
AUPQ514600A0 (en) 2000-01-18 2000-02-10 James Cook University Brain injury treatment
AU3580001A (en) 2000-03-01 2001-09-12 University College London Modulators of the endocannabinoid uptake and of the vallinoid receptors
DE10015248A1 (de) 2000-03-28 2001-10-04 Merck Patent Gmbh Bisamidino-Verbindungen als NHE-3 Inhibitoren
DE10019062A1 (de) 2000-04-18 2001-10-25 Merck Patent Gmbh 2-Guanidino-4-aryl-chinazoline als NHE-3 Inhibitoren
US20030212074A1 (en) 2000-05-02 2003-11-13 Dimitri Gaitanopoulos Phosphate transport inhibitors
AU2001261471A1 (en) 2000-05-12 2001-11-26 Smithkline Beecham Corporation Phosphate transport inhibitors
DE10043667A1 (de) 2000-09-05 2002-03-14 Merck Patent Gmbh 2-Guanidino-4-aryl-chinazoline
US6414016B1 (en) 2000-09-05 2002-07-02 Sucampo, A.G. Anti-constipation composition
DE10046993A1 (de) 2000-09-22 2002-04-11 Aventis Pharma Gmbh Substituierte Zimtsäureguanidide, Verfahren zur ihrer Herstellung, ihre Verwendung als Medikament sowie sie enthaltendes Medikament
AU2002213048A1 (en) 2000-10-05 2002-04-15 Smith Kline Beecham Corporation Phosphate transport inhibitors
WO2002040039A2 (en) 2000-11-20 2002-05-23 Dow Global Technologies Inc. In vivo use of water absorbent polymers
DE10063294A1 (de) 2000-12-19 2002-07-04 Aventis Pharma Gmbh Substituierte Heterocyclo-Norbornylamino-Derivate, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament
WO2002078683A1 (en) 2001-03-29 2002-10-10 Synergy Pharmaceuticals, Inc. Guanylate cyclase receptor agonists for the treatment of tissue inflammation and carcinogenesis
US6736705B2 (en) 2001-04-27 2004-05-18 Hitachi Global Storage Technologies Polishing process for glass or ceramic disks used in disk drive data storage devices
MY134211A (en) 2001-05-18 2007-11-30 Smithkline Beecham Corp Novel use
JP2007131532A (ja) 2001-09-28 2007-05-31 Kirin Brewery Co Ltd 生体内リン輸送を阻害する化合物およびそれを含んでなる医薬
FR2830451B1 (fr) 2001-10-09 2004-04-30 Inst Nat Sante Rech Med Utilisation de peptides analogues de la thymuline(pat)pour la fabrication de medicaments contre la douleur
US6911453B2 (en) 2001-12-05 2005-06-28 Aventis Pharma Deutschland Gmbh Substituted 4-phenyltetrahydroisoquinolinium, process for their preparation, their use as a medicament, and medicament containing them
DK1453810T3 (da) * 2001-12-05 2009-07-20 Sanofi Aventis Deutschland Substituerede 4-phenyltetrahydroisoquinoliner, fremgangsmåde til deres fremstilling, deres anvendelse som medikament indeholdende samme
AU2002354410A1 (en) 2001-12-05 2003-06-17 Japan Tobacco Inc. Triazole compound and medicinal use thereof
DE10161767A1 (de) 2001-12-15 2003-06-26 Merck Patent Gmbh 2-Guanidino-4-heterocyclyl-chinazoline
EP1321142A1 (en) 2001-12-21 2003-06-25 Novartis AG Solid pharmaceutical composition for oral administration of Tegaserod
US6703405B2 (en) 2001-12-22 2004-03-09 Aventis Pharma Deutschland Gmbh Substituted 4-phenyltetrahydroisoquinolinium salts, process for their preparation, their use as a medicament, and medicament containing them
DE10163914A1 (de) * 2001-12-22 2003-07-03 Aventis Pharma Gmbh Substituierte 4-Phenyltetrahydroisochinolinium-Salze, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament, sowie sie enthaltendes Medikament
DE10163992A1 (de) 2001-12-24 2003-07-03 Merck Patent Gmbh 4-Aryl-chinazoline
US7119120B2 (en) 2001-12-26 2006-10-10 Genzyme Corporation Phosphate transport inhibitors
WO2003077897A1 (en) 2002-03-15 2003-09-25 Cypress Bioscience, Inc. Ne and 5-ht reuptake inhibitors for treating visceral pain syndromes
EP1485391B1 (en) 2002-03-19 2006-08-23 Genzyme Corporation Phosphate transport inhibitors
CN100411618C (zh) 2002-05-17 2008-08-20 迪欧加药品公司 有效的选择性阿片受体调制剂化合物的用途
US7014862B2 (en) 2002-05-20 2006-03-21 The Procter & Gamble Company Chewable compositions containing a gel-forming extract of psyllium
TWI245308B (en) 2002-09-13 2005-12-11 Getters Spa Non-evaporable getter compositions which can be reactivated at low temperature after exposure to reactive gases at a higher temperature
CN1254051C (zh) 2002-10-25 2006-04-26 华为技术有限公司 城域网传输设备中用户数据业务子速率传送方法
US6923466B2 (en) 2002-12-17 2005-08-02 James Tsai Collapsible handcart capable of extending the area of carrier by operating handle
US7304036B2 (en) 2003-01-28 2007-12-04 Microbia, Inc. Methods and compositions for the treatment of gastrointestinal disorders
US20050054705A1 (en) 2003-02-04 2005-03-10 Aventis Pharma Deutschland Gmbh N-substituted (benzoimidazol-2-yl) phenylamines, process for their preparation, their use as medicament or diagnostic aid, and medicament comprising them
US7026303B2 (en) 2003-02-18 2006-04-11 The Procter & Gamble Company Compositions comprising a polysaccharide component and one or more coating layers
WO2004085448A2 (en) 2003-03-19 2004-10-07 Genzyme Corporation Unsaturated phosphinyl-phosphonate phosphate transport inhibitors
US7241775B2 (en) 2003-03-24 2007-07-10 Sanofi-Aventis Deutschland Gmbh Composition, process of making, and medical use of substituted 4-phenyltetrahydroisoquinolines
DE10312963A1 (de) * 2003-03-24 2004-10-07 Aventis Pharma Deutschland Gmbh Substituierte 4-Phenyltetrahydroisochinoline, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament, sowie sie enthaltendes Medikament
WO2004085382A1 (ja) 2003-03-27 2004-10-07 Kirin Beer Kabushiki Kaisha 生体内リン輸送を阻害する化合物およびそれを含んでなる医薬
US8338074B2 (en) 2003-06-25 2012-12-25 Cmet Inc. Actinic radiation-curable stereolithographic resin composition having improved stability
WO2005020612A1 (en) 2003-08-20 2005-03-03 Musky Communications (Proprietary) Limited Telephonic communication
PE20050952A1 (es) * 2003-09-24 2005-12-19 Novartis Ag Derivados de isoquinolina como inhibidores de b-raf
US20050095578A1 (en) 2003-10-31 2005-05-05 Koller Manfred R. Method and apparatus for cell permeabilization
WO2005054705A2 (en) 2003-11-26 2005-06-16 Brian Judd Apparatus for dampening impact vibration in manual tools
US20050244367A1 (en) 2004-05-03 2005-11-03 Ilypsa, Inc. Phospholipase inhibitors localized in the gastrointestinal lumen
EP1748944A4 (en) 2004-05-14 2010-10-06 Paceco Corp METHOD AND DEVICE FOR PRODUCING STATUS REPORTING DEVICES FOR CONTAINER TRANSPORTERS
US8173596B2 (en) 2004-05-14 2012-05-08 The University Of North Carolina At Chapel Hill Prouroguanylin, and synthetic analogs or proteolytic cleavage products derived from it, as therapeutic and diagnostic agents for diseases involving salt and/or fluid homeostasis
DE102004046492A1 (de) * 2004-09-23 2006-03-30 Sanofi-Aventis Deutschland Gmbh Substituierte 4-Phenyltetrahydroisochinoline, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament, sowie sie enthaltendes Medikament
US20070054916A1 (en) * 2004-10-01 2007-03-08 Amgen Inc. Aryl nitrogen-containing bicyclic compounds and methods of use
WO2006039824A1 (en) 2004-10-13 2006-04-20 Rolic Ag Photocrosslinkable materials
DE102004054847A1 (de) 2004-11-13 2006-05-24 Sanofi-Aventis Deutschland Gmbh Substituierte Benzoylguanidine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament
DE102005001411A1 (de) * 2005-01-12 2006-07-27 Sanofi-Aventis Deutschland Gmbh Substituierte 4-Phenyltetrahydroisochinoline, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament, sowie sie enthaltendes Medikament
CA2619977C (en) 2005-08-29 2011-06-28 Demain Technology Pty Ltd. Power tool
DE102005044815A1 (de) * 2005-09-20 2007-03-22 Sanofi-Aventis Deutschland Gmbh Verwendung von Inhibitoren des Na+/H+ Austauschers, Subtyp 5 (NHE5) zur Gedächtnisverbesserung
DE102005044817A1 (de) 2005-09-20 2007-03-22 Sanofi-Aventis Deutschland Gmbh Substituierte 4-Phenyltetrahydroisochinoline, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament, sowie sie enthaltendes Medikament
AU2006311765A1 (en) * 2005-11-03 2007-05-18 Ilypsa, Inc. Phospholipase inhibitors, including multi-valent phospholipase inhibitors, and use thereof, including as lumen-localized phospholipase inhibitors
US7666898B2 (en) 2005-11-03 2010-02-23 Ilypsa, Inc. Multivalent indole compounds and use thereof as phospholipase-A2 inhibitors
US7694181B2 (en) 2005-12-12 2010-04-06 Archivas, Inc. Automated software testing framework
GB0610009D0 (en) 2006-05-19 2006-06-28 Health Prot Agency Culture medium
GB2438389A (en) 2006-05-23 2007-11-28 Gkn Aerospace Transparency Sys Heating system for leading edge of aircraft
US20120283411A9 (en) 2006-06-29 2012-11-08 Ironwood Pharmaceuticals, Inc. Methods and compositions for the treatment of gastrointestinal disorders
US8617903B2 (en) 2007-01-29 2013-12-31 The Invention Science Fund I, Llc Methods for allergen detection
US8779090B2 (en) 2007-02-26 2014-07-15 Ironwood Pharmaceuticals, Inc. Methods and compositions for the treatment of heart failure and other disorders
MX2009011898A (es) 2007-05-04 2009-11-18 Ironwood Pharmaceuticals Inc Composiciones y metodos para tratar trastornos asociados con retencion de sal o fluido.
ES2657938T3 (es) * 2008-12-31 2018-03-07 Ardelyx, Inc. Compuestos y métodos para inhibir el antipuerto mediado por NHE en el tratamiento de trastornos asociados a la retención de líquidos o a la sobrecarga de sales y trastornos del tracto gastrointestinal

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