WO2001087294A1 - Inhibiteurs du transport de phosphate - Google Patents

Inhibiteurs du transport de phosphate Download PDF

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Publication number
WO2001087294A1
WO2001087294A1 PCT/US2001/015324 US0115324W WO0187294A1 WO 2001087294 A1 WO2001087294 A1 WO 2001087294A1 US 0115324 W US0115324 W US 0115324W WO 0187294 A1 WO0187294 A1 WO 0187294A1
Authority
WO
WIPO (PCT)
Prior art keywords
benzamide
bromophenyl
bromo
chlorophenyl
group
Prior art date
Application number
PCT/US2001/015324
Other languages
English (en)
Inventor
Joseph Weinstock
Gerald Girard
Dimitri Gaitanopoulos
Original Assignee
Smithkline Beecham Corporation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to HU0302234A priority Critical patent/HUP0302234A2/hu
Priority to BR0110034-3A priority patent/BR0110034A/pt
Priority to AU2001261471A priority patent/AU2001261471A1/en
Priority to US10/275,661 priority patent/US20030216449A1/en
Priority to CA002408667A priority patent/CA2408667A1/fr
Priority to MXPA02011160A priority patent/MXPA02011160A/es
Application filed by Smithkline Beecham Corporation filed Critical Smithkline Beecham Corporation
Priority to JP2001583762A priority patent/JP2003533477A/ja
Priority to IL15258701A priority patent/IL152587A0/xx
Priority to KR1020027015094A priority patent/KR20020093983A/ko
Priority to PL35993101A priority patent/PL359931A1/xx
Publication of WO2001087294A1 publication Critical patent/WO2001087294A1/fr
Priority to NO20025399A priority patent/NO20025399D0/no

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/18—Sulfonamides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention involves the treatment of chronic renal failure, uremic bone disease and related diseases by inhibition of phosphate retention by certain N- aryl-2-sulfonamidobenzamides.
  • ESRD end stage renal disease
  • Chronic renal failure affects more than 270,000 patients in the US alone and costs an estimated $6.8 billion in annual heath care costs.
  • CRF Chronic renal failure
  • Early and major contributors to the morbidity of CRF patients are abnormalities in electrolyte and bone metabolism induced by the progressive loss of renal excretory function.
  • Phosphate (Pi) retention has been identified as playing a major role in the progression of CRF and in the development of uremic bone disease.
  • the present invention involves novel methods of using of N-aryl-2- sulfonamidobenzamides as phosphate transport inhibitors for the selective inhibition of Pi transport in the kidney and/or the intestine as a therapeutic treatment in chronic renal failure and uremic bone disease.
  • the present invention involves the use of inhibitors of phosphate transport, for the treatment of chronic renal failure, and uremic bone disease, as well as other related diseases, such as hyperphosphatemia, vitamin D metabolism, and secondary hyperparathyroidism caused by the retention of phosphate.
  • inhibitors for use herein are those which selectively inhibit Na + -dependent Pi transport in tissues, preferably renal and intestinal tissue, from a number of species, including human.
  • the present invention relates to the use of compounds that are inhibitors of sodium-dependent phosphate transport, which are represented by the following Formula (I):
  • R and R2 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, arylalkyl, acyl, aroyl, haloalkyl, aryl, heteroaryl, halo, carboxy, carboalkoxy, carbamyl, alkylcarbamyl, arylcarbamyl, cyano, alkoxy, hydroxyl, phenylazo, amino, nitro, alkylamino, arylamino, arylalkyl amino, acylamino, aroylamino, alkylthio, arylalkylthio, arylthio, alkysulfinyl, arylsulfinyl, arylalkylsulfinyl, alkylsulfonyl, arylsulfonyl, arylalkylsulfonyl, sulfamyl, arylsulfonamido, and alkyl
  • R3 is independently selected from the group consisting of alkyl, haloalkyl, R ⁇ aryl and R aralkyl, and Rjsubstituted heterocycles selected from the group consisting of thiophene, furan, pyridine, pyrimidine, pyrazine, imidazole, and thiazole, isoxazole, thiadiazole, oxadiazole, and benzo analogs thereof.
  • alkyl refers to an optionally substituted hydrocarbon group joined together by single carbon-carbon bonds. Preferred alkyl substituents are as indicated throughout.
  • the alkyl hydrocarbon group may be linear, branched or cyclic, saturated or unsaturated.
  • aryl refers to an optionally substituted aromatic group with at least one ring having a conjugated pi-electron system, containing up to two conjugated or fused ring systems.
  • Aryl includes carbocyclic aryl, heterocyclic aryl and biaryl groups, all of which may be optionally substituted. Preferred aryl substituents are as indicated throughout.
  • the compounds of the present invention may contain one or more asymmetric carbon atoms and may exist in racemic and optically active forms. All of these compounds and diastereomers are contemplated to be within the scope of the present invention.
  • Preferred compounds include, but are not limited to:
  • salts for use when basic groups are present include acid addition salts such as those containing sulfate, hydrochloride, fumarate, maleate, phosphate, sulfamate, acetate, citrate, lactate, tartrate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, cyclohexylsulfamate and quinate.
  • Pharmaceutically acceptable salts can be obtained from acids such as hydrochloric acid, maleic acid, sulfuric acid, phosphoric acid, sulfamic acid, acetic acid, citric acid, lactic acid, tartaric acid, malonic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, -toluenesulfonic acid, cyclohexylsulfamic acid, fumaric acid, and quinic acid.
  • acids such as hydrochloric acid, maleic acid, sulfuric acid, phosphoric acid, sulfamic acid, acetic acid, citric acid, lactic acid, tartaric acid, malonic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, -toluenesulfonic acid, cyclohexylsulfamic acid, fumaric acid, and quinic acid.
  • Pharmaceutically acceptable salts also include basic addition salts such as those containing benzathine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine, procaine, aluminum, calcium, lithium, magnesium, potassium, sodium, ammonium, alkylamine, and zinc, when acidic functional groups, such as carboxylic acid or phenol are present.
  • the present invention provides compounds of Formula (I) above which can be prepared using standard techniques.
  • An overall strategy for preparing preferred compounds described herein can be carried out as described in this section. Using the protocols described herein as a model, one of ordinary skill in the art can readily produce other compounds of the present invention.
  • a compound of Formula (I) or a pharmaceutically acceptable salt thereof for the treatment of humans and other mammals, it is normally formulated in accordance with standard pharmaceutical practice as a pharmaceutical composition.
  • the present compounds can be administered by different routes including intravenous, intraperitoneal, subcutaneous, intramuscular, oral, topical (transdermal), or transmucosal administration.
  • oral administration is preferred.
  • the compounds can be formulated into conventional oral dosage forms such as capsules, tablets, and liquid preparations such as syrups, elixirs, and concentrated drops.
  • injection parenteral administration
  • the compounds of the invention are formulated in liquid solutions, preferably, in physiologically compatible buffers or solutions, such as saline solution, Hank's solution, or Ringer's solution.
  • the compounds may be formulated in solid form and re-dissolved or suspended immediately prior to use. Lyophilized forms can also be produced.
  • Systemic administration can also be by transmucosal or transdermal means.
  • penetrants appropriate to the barrier to be permeated are used in the formulation.
  • penetrants are generally known in the art, and include, ' for example, for transmucosal administration, bile salts and fusidic acid derivatives.
  • detergents may be used to facilitate permeation.
  • Transmucosal administration for example, may be through nasal sprays, rectal suppositories, or vaginal suppositories.
  • the compounds of the invention can be formulated into ointments, salves, gels, or creams, as is generally known in the art.
  • the amounts of various compounds to be administered can be determined by standard procedures taking into account factors such as the compound IC50, EC50, the biological half-life of the compound, the age, size and weight of the patient, and the disease or disorder associated with the patient. The importance of these and other factors to be considered are known to those of ordinary skill in the art.
  • Amounts administered also depend on the routes of administration and the degree of oral bioavailability. For example, for compounds with low oral bioavailability, relatively higher doses will have to be administered.
  • the composition is in unit dosage form.
  • a tablet, or capsule may be administered, for nasal application, a metered aerosol dose may be administered, for transdermal application, a topical formulation or patch may be administered and for transmucosal delivery, a buccal patch may be administered.
  • dosing is such that the patient may administer a single dose.
  • Each dosage unit for oral administration contains suitably from 0.01 to 500 mg/Kg, and preferably from 0.1 to 50 mg/Kg, of a compound of Formula (I) or a pharmaceutically acceptable salt thereof, calculated as the free base.
  • the daily dosage for parenteral, nasal, oral inhalation, transmucosal or transdermal routes contains suitably from 0.01 mg to 100 mg/Kg, of a compound of Formula (I).
  • a topical formulation contains suitably 0.01 to 5.0% of a compound of Formula (I).
  • the active ingredient may be administered from 1 to 6 times per day, preferably once, sufficient to exhibit the desired activity, as is readily apparent to one skilled in the art.
  • composition of Formula (I) and their pharmaceutically acceptable salts which are active when given orally can be formulated as syrups, tablets, capsules and lozenges.
  • a syrup formulation will generally consist of a suspension or solution of the compound or salt in a liquid carrier for example, ethanol, peanut oil. olive oil, glycerine or water with a flavoring or coloring agent.
  • a liquid carrier for example, ethanol, peanut oil. olive oil, glycerine or water with a flavoring or coloring agent.
  • any pharmaceutical carrier routinely used for preparing solid formulations may be used.
  • any routine encapsulation is suitable, for example using the aforementioned carriers in a hard gelatin capsule shell.
  • any pharmaceutical carrier routinely used for preparing dispersions or suspensions may be considered, for example aqueous gums, celluloses, silicates or oils, and are incorporated in a soft gelatin capsule shell.
  • Typical parenteral compositions consist of a solution or suspension of a compound or salt in a sterile aqueous or non-aqueous carrier optionally containing a parenterally acceptable oil, for example polyethylene glycol, polyvinylpyrrolidone, lecithin, arachis oil or sesame oil.
  • a parenterally acceptable oil for example polyethylene glycol, polyvinylpyrrolidone, lecithin, arachis oil or sesame oil.
  • compositions for inhalation are in the form of a solution, suspension or emulsion that may be administered as a dry powder or in the form of an aerosol using a conventional propellant such as dichlorodifluoromethane or trichlorofTuoromefhane.
  • a typical suppository formulation comprises a compound of Formula (I) or a pharmaceutically acceptable salt thereof which is active when administered in this way, with a binding and/or lubricating agent, for example polymeric glycols, gelatins, cocoa-butter or other low melting vegetable waxes or fats or their synthetic analogs.
  • a binding and/or lubricating agent for example polymeric glycols, gelatins, cocoa-butter or other low melting vegetable waxes or fats or their synthetic analogs.
  • Typical dermal and transdermal formulations comprise a conventional aqueous or non-aqueous vehicle, for example a cream, ointment, lotion or paste or are in the form of a medicated plaster, patch or membrane.
  • a conventional aqueous or non-aqueous vehicle for example a cream, ointment, lotion or paste or are in the form of a medicated plaster, patch or membrane.
  • the composition is in unit dosage form, for example a tablet, capsule or metered aerosol dose, so that the patient may administer a single dose.
  • Sodium-dependent phosphate transport inhibition is determined by the ability of the test compound to inhibit the uptake of radio-labeled inorganic phosphate by proximal tubule cells. Appropriate cells from human, rabbit, or rat may be used.
  • Rabbit proximal tubule cells were isolated and cultured according to the procedure of Sakhrani, L. M. et al., Am. J. Physiol. 246:F757-F764, (1984) whose disclosure is incorporated herein by reference in its entirety.
  • Human proximal tubule cells were purchased from Clonetics (San Diego, CA) and grown according to the suppliers' instructions. On the day of the experiment, cells were harvested from culture plates with 0.5 mM EDTA in phosphate buffered saline. The cells were washed twice in uptake buffer (see below) and equilibrated at 37 C in the same buffer for 30 minutes. Aliquots of cells (100 ul, 0.5 to 1 million cells) were distributed into glass test tubes. Fifty ul of drug solution or buffer were added
  • uptake buffer containing 100 uM [ P]-K2HPO4 ( 0.5 to 1 uCi/tube) .
  • uptakes were stopped with 4 ml of cold stop solution (see below) and the cells were washed 3 times in this solution by centrifugation. The pelleted cells were dissolved in 0.5 ml IN NaOH and 32 P was counted in a liquid scintillation counter. Phosphate uptake is expressed as pmol phosphate/mg cell protein.
  • the cells are harvested by filtration and 32p uptake is measured. It is also possible to use 33p rather than 32p.
  • the IC50 for 5-bromo-N-(4-bromophenyl)-2-(5-chloro-2- thienylsulfonamido)benzamide, 5-bromo-N-(4-bromophenyl)-2-(2- fluorophenylsulfonamido)benzamide, and 5-bromo-N-(4-bromophenyl)-2-(3- chloropropylsulfonamido)benzamide are 12, 15, and 14 ⁇ M respectively.
  • Example 1 N-(4-Bromophenyl)-2-amino-5-bromobenzamide A 11.6 ml portion of a 2.0 M solution of trimethylaluminum (23.2 mmol) was added to a solution of 4.0 g (23.25 mmol) of 4-bromoaniline at 0° C. The reaction mixture was held at ambient temperature for 45 min, and then cooled to 0° C. Methyl 2-amino-5-bromobenzoate (4.72 g, 23.25 mmol) was added in small portions, and after a vigorous gas evolution ceased the reaction mixture was held at ambient temperature for 18 hr.

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  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Urology & Nephrology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Epidemiology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Rheumatology (AREA)
  • Obesity (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

La présente invention concerne des N-Aryl-2-sulfonamidobenzamides utilisés dans le traitement de l'insuffisance rénale chronique et de la maladie osseuse urémique.
PCT/US2001/015324 2000-05-12 2001-05-11 Inhibiteurs du transport de phosphate WO2001087294A1 (fr)

Priority Applications (11)

Application Number Priority Date Filing Date Title
BR0110034-3A BR0110034A (pt) 2000-05-12 2001-05-11 Inibidores do transporte de fosfatos
AU2001261471A AU2001261471A1 (en) 2000-05-12 2001-05-11 Phosphate transport inhibitors
US10/275,661 US20030216449A1 (en) 2001-05-11 2001-05-11 Phosphate transport inhibitors
CA002408667A CA2408667A1 (fr) 2000-05-12 2001-05-11 Inhibiteurs du transport de phosphate
MXPA02011160A MXPA02011160A (es) 2000-05-12 2001-05-11 Inhibidores del transporte de fosfato.
HU0302234A HUP0302234A2 (hu) 2000-05-12 2001-05-11 Foszfát-transzport inhibitorok, ezeket tartalmazó gyógyszerkészítmények és alkalmazásuk
JP2001583762A JP2003533477A (ja) 2000-05-12 2001-05-11 リン酸輸送阻害剤
IL15258701A IL152587A0 (en) 2000-05-12 2001-05-11 Phosphate transport inhibitors
KR1020027015094A KR20020093983A (ko) 2000-05-12 2001-05-11 포스페이트 수송 억제제
PL35993101A PL359931A1 (en) 2000-05-12 2001-05-11 Phosphate transport inhibitors
NO20025399A NO20025399D0 (no) 2000-05-12 2002-11-11 Fosfat transport inhibitorer

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US20399500P 2000-05-12 2000-05-12
US60/203,995 2000-05-12

Publications (1)

Publication Number Publication Date
WO2001087294A1 true WO2001087294A1 (fr) 2001-11-22

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PCT/US2001/015324 WO2001087294A1 (fr) 2000-05-12 2001-05-11 Inhibiteurs du transport de phosphate

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JP (1) JP2003533477A (fr)
KR (1) KR20020093983A (fr)
CN (1) CN1429108A (fr)
AU (1) AU2001261471A1 (fr)
BR (1) BR0110034A (fr)
CA (1) CA2408667A1 (fr)
CZ (1) CZ20023701A3 (fr)
HU (1) HUP0302234A2 (fr)
IL (1) IL152587A0 (fr)
MX (1) MXPA02011160A (fr)
NO (1) NO20025399D0 (fr)
PL (1) PL359931A1 (fr)
WO (1) WO2001087294A1 (fr)
ZA (1) ZA200209106B (fr)

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2378179A (en) * 2001-08-03 2003-02-05 Pantherix Ltd Aromatic sulfonamides and their use in treating bacterial diseases
WO2003057225A2 (fr) * 2001-12-26 2003-07-17 Genzyme Corporation Inhibiteurs de transport du phosphate
WO2014029983A1 (fr) 2012-08-21 2014-02-27 Ardelyx, Inc. Composés et procédés d'inhibition d'un antiport à médiation par nhe dans le traitement de troubles associés à une rétention de fluide ou à une surcharge de sel et de troubles du tractus gastro-intestinal
US9765050B2 (en) 2014-12-30 2017-09-19 Novira Therapeutics, Inc. Pyridyl reverse sulfonamides for HBV treatment
WO2018043400A1 (fr) * 2016-08-30 2018-03-08 日本曹達株式会社 Composé benzamide de sulfonylamino et agent de lutte antiparasitaire
WO2018129557A1 (fr) 2017-01-09 2018-07-12 Ardelyx, Inc. Inhibiteurs d'antiport à médiation par nhe
WO2018129556A1 (fr) 2017-01-09 2018-07-12 Ardelyx, Inc. Composés et procédés pour l'inhibition d'un antiport à médiation par échangeur sodium/proton (nhe) dans le traitement de troubles associés à une rétention d'eau ou à une surcharge en sel et de troubles du tractus gastro-intestinal
WO2018129552A1 (fr) 2017-01-09 2018-07-12 Ardelyx, Inc. Composés utiles pour le traitement de troubles du tractus digestif
EP3351248A1 (fr) 2008-12-31 2018-07-25 Ardelyx, Inc. Composés et procédés d'inhibition d'un antiport à médiation par nhe dans le traitement de troubles associés à une rétention de fluide ou à une surcharge de sel et de troubles du tractus gastro-intestinal
US10272079B2 (en) 2013-04-12 2019-04-30 Ardelyx, Inc. NHE3-binding compounds and methods for inhibiting phosphate transport
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
WO2019232384A1 (fr) * 2018-06-01 2019-12-05 Promega Corporation Inhibiteurs de complexes bioluminescents dérivés de la luciférase oplophorus

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CN103183623A (zh) * 2013-03-12 2013-07-03 中国医学科学院医药生物技术研究所 一组苯磺酰胺基苯甲酰胺类衍生物及制备和应用
CN105395532B (zh) * 2015-11-25 2017-11-14 中国医学科学院医药生物技术研究所 2‑苯磺酰胺基苯甲酰胺类化合物在肝损伤保护和肝纤维化防治中的应用

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WO2000078145A1 (fr) * 1999-06-24 2000-12-28 Smithkline Beecham Corporation Antagonistes du recepteur destructeur de macrophage
WO2001005398A1 (fr) * 1999-07-20 2001-01-25 Smithkline Beecham Corporation Inhibiteurs de transport de phosphate

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WO2000078145A1 (fr) * 1999-06-24 2000-12-28 Smithkline Beecham Corporation Antagonistes du recepteur destructeur de macrophage
WO2001005398A1 (fr) * 1999-07-20 2001-01-25 Smithkline Beecham Corporation Inhibiteurs de transport de phosphate

Non-Patent Citations (1)

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DATABASE PCTFULL [online] EDWARDS ET AL., XP002946414, Database accession no. 2001005398 *

Cited By (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2378179A (en) * 2001-08-03 2003-02-05 Pantherix Ltd Aromatic sulfonamides and their use in treating bacterial diseases
US7119120B2 (en) 2001-12-26 2006-10-10 Genzyme Corporation Phosphate transport inhibitors
EP1815860A2 (fr) 2001-12-26 2007-08-08 Genzyme Corporation Inhibiteurs de transport du phosphate
WO2003057225A2 (fr) * 2001-12-26 2003-07-17 Genzyme Corporation Inhibiteurs de transport du phosphate
WO2003057225A3 (fr) * 2001-12-26 2004-04-08 Genzyme Corp Inhibiteurs de transport du phosphate
JP2005514413A (ja) * 2001-12-26 2005-05-19 ジェンザイム コーポレーション リン酸塩輸送インヒビター
EP1815860A3 (fr) * 2001-12-26 2007-11-21 Genzyme Corporation Inhibiteurs de transport du phosphate
EP3939964A1 (fr) 2008-12-31 2022-01-19 Ardelyx, Inc. Combinaisons d'inhibition d'un antiport a mediation par nhe dans le traitement de troubles associes a une retention de fluide ou a une surcharge de sel et de troubles du tractus gastro-intestinal
EP3351248A1 (fr) 2008-12-31 2018-07-25 Ardelyx, Inc. Composés et procédés d'inhibition d'un antiport à médiation par nhe dans le traitement de troubles associés à une rétention de fluide ou à une surcharge de sel et de troubles du tractus gastro-intestinal
WO2014029983A1 (fr) 2012-08-21 2014-02-27 Ardelyx, Inc. Composés et procédés d'inhibition d'un antiport à médiation par nhe dans le traitement de troubles associés à une rétention de fluide ou à une surcharge de sel et de troubles du tractus gastro-intestinal
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
US10940146B2 (en) 2013-04-12 2021-03-09 Ardelyx, Inc. NHE3-binding compounds and methods for inhibiting phosphate transport
US10272079B2 (en) 2013-04-12 2019-04-30 Ardelyx, Inc. NHE3-binding compounds and methods for inhibiting phosphate transport
US9765050B2 (en) 2014-12-30 2017-09-19 Novira Therapeutics, Inc. Pyridyl reverse sulfonamides for HBV treatment
US10160742B2 (en) 2014-12-30 2018-12-25 Novira Therapeutics, Inc. Pyridyl reverse sulfonamides for HBV treatment
US10428041B2 (en) 2014-12-30 2019-10-01 Novira Therapeutics, Inc. Pyridyl reverse sulfonamides for HBV treatment
US10793520B2 (en) 2016-08-30 2020-10-06 Nippon Soda Co., Ltd. Sulfonylaminobenzamide compound and pest control agent
WO2018043400A1 (fr) * 2016-08-30 2018-03-08 日本曹達株式会社 Composé benzamide de sulfonylamino et agent de lutte antiparasitaire
WO2018129552A1 (fr) 2017-01-09 2018-07-12 Ardelyx, Inc. Composés utiles pour le traitement de troubles du tractus digestif
WO2018129556A1 (fr) 2017-01-09 2018-07-12 Ardelyx, Inc. Composés et procédés pour l'inhibition d'un antiport à médiation par échangeur sodium/proton (nhe) dans le traitement de troubles associés à une rétention d'eau ou à une surcharge en sel et de troubles du tractus gastro-intestinal
US11147884B2 (en) 2017-01-09 2021-10-19 Ardelyx, Inc. Inhibitors of NHE-mediated antiport
WO2018129557A1 (fr) 2017-01-09 2018-07-12 Ardelyx, Inc. Inhibiteurs d'antiport à médiation par nhe
US11242337B2 (en) 2017-01-09 2022-02-08 Ardelyx, Inc. Compounds useful for treating gastrointestinal tract disorders
WO2019232384A1 (fr) * 2018-06-01 2019-12-05 Promega Corporation Inhibiteurs de complexes bioluminescents dérivés de la luciférase oplophorus
US11390599B2 (en) 2018-06-01 2022-07-19 Promega Corporation Inhibitors of oplophorus luciferase-derived bioluminescent complexes

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HUP0302234A2 (hu) 2003-11-28
BR0110034A (pt) 2003-05-27
CN1429108A (zh) 2003-07-09
KR20020093983A (ko) 2002-12-16
NO20025399L (no) 2002-11-11
ZA200209106B (en) 2003-10-23
CZ20023701A3 (cs) 2003-11-12
JP2003533477A (ja) 2003-11-11
AU2001261471A1 (en) 2001-11-26
IL152587A0 (en) 2003-05-29
NO20025399D0 (no) 2002-11-11
CA2408667A1 (fr) 2001-11-22
MXPA02011160A (es) 2003-03-10
PL359931A1 (en) 2004-09-06

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