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DE60317884T8 - Natriumkanalblocker - Google Patents

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Publication number
DE60317884T8
DE60317884T8 DE60317884T DE60317884T DE60317884T8 DE 60317884 T8 DE60317884 T8 DE 60317884T8 DE 60317884 T DE60317884 T DE 60317884T DE 60317884 T DE60317884 T DE 60317884T DE 60317884 T8 DE60317884 T8 DE 60317884T8
Authority
DE
Germany
Prior art keywords
sodium channel
channel blocker
sup
formula
compounds
Prior art date
Legal status (The legal status 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 status listed.)
Active
Application number
DE60317884T
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English (en)
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DE60317884D1 (de
DE60317884T2 (de
Inventor
Michael R. Chapel Hills JOHNSON
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Parion Sciences Inc
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Parion Sciences Inc
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
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Publication of DE60317884D1 publication Critical patent/DE60317884D1/de
Application granted granted Critical
Publication of DE60317884T2 publication Critical patent/DE60317884T2/de
Publication of DE60317884T8 publication Critical patent/DE60317884T8/de
Active legal-status Critical Current

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4965Non-condensed pyrazines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/06Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/10Laxatives
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/02Nasal agents, e.g. decongestants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/06Antiasthmatics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/12Mucolytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00Drugs for genital or sexual disorders; Contraceptives
    • A61P15/02Drugs for genital or sexual disorders; Contraceptives for disorders of the vagina
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/16Otologicals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/10Antioedematous agents; Diuretics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/12Antihypertensives
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D241/00Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/14Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D241/24Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D241/26Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pulmonology (AREA)
  • Reproductive Health (AREA)
  • Gynecology & Obstetrics (AREA)
  • Ophthalmology & Optometry (AREA)
  • Cardiology (AREA)
  • Diabetes (AREA)
  • Dermatology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Endocrinology (AREA)
  • Otolaryngology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
DE60317884T 2002-02-19 2003-02-19 Natriumkanalblocker Active DE60317884T8 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US76551 2002-02-19
US10/076,551 US6858614B2 (en) 2002-02-19 2002-02-19 Phenolic guanidine sodium channel blockers
PCT/US2003/004823 WO2003070184A2 (en) 2002-02-19 2003-02-19 Sodium channel blockers

Publications (3)

Publication Number Publication Date
DE60317884D1 DE60317884D1 (de) 2008-01-17
DE60317884T2 DE60317884T2 (de) 2009-01-02
DE60317884T8 true DE60317884T8 (de) 2009-06-04

Family

ID=27752676

Family Applications (1)

Application Number Title Priority Date Filing Date
DE60317884T Active DE60317884T8 (de) 2002-02-19 2003-02-19 Natriumkanalblocker

Country Status (13)

Country Link
US (6) US6858614B2 (de)
EP (1) EP1485359B1 (de)
JP (1) JP2005526726A (de)
KR (1) KR20040091065A (de)
AT (1) ATE380181T1 (de)
AU (1) AU2003215286A1 (de)
CA (1) CA2476837A1 (de)
CY (1) CY1107228T1 (de)
DE (1) DE60317884T8 (de)
DK (1) DK1485359T3 (de)
ES (1) ES2298505T3 (de)
PT (1) PT1485359E (de)
WO (1) WO2003070184A2 (de)

Families Citing this family (49)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6858615B2 (en) * 2002-02-19 2005-02-22 Parion Sciences, Inc. Phenyl guanidine sodium channel blockers
US6858614B2 (en) * 2002-02-19 2005-02-22 Parion Sciences, Inc. Phenolic guanidine sodium channel blockers
US6903105B2 (en) 2003-02-19 2005-06-07 Parion Sciences, Inc. Sodium channel blockers
US7375107B2 (en) * 2003-08-18 2008-05-20 Parion Sciences, Inc. Alaphatic pyrazinoylguanidine sodium channel blockers
WO2005016879A2 (en) * 2003-08-18 2005-02-24 Parion Sciences, Inc. Cyclic pyrazinoylguanidine sodium channel blockers
US7064129B2 (en) * 2003-08-18 2006-06-20 Parion Sciences, Inc. Capped pyrazinoylguanidine sodium channel blockers
US20090253714A1 (en) * 2003-08-20 2009-10-08 Johnson Michael R Methods of reducing risk of infection from pathogens
US7745442B2 (en) * 2003-08-20 2010-06-29 Parion Sciences, Inc. Methods of reducing risk of infection from pathogens
CN1882353B (zh) * 2003-11-19 2011-04-20 明治制果株式会社 催涎剂和混合该催涎剂的口腔用组合物以及食品组合物
US7399766B2 (en) * 2004-08-18 2008-07-15 Parion Sciences, Inc. Soluble amide & ester pyrazinoylguanidine sodium channel blockers
EP1789049A4 (de) 2004-08-18 2009-07-22 Michael R Johnson Cyklische amid- und esterpyrazinoylguanidin-natriumkanalblocker
US7956059B2 (en) * 2004-08-18 2011-06-07 Parion Sciences, Inc. Aliphatic amide and ester pyrazinoylguanidine sodium channel blockers
US8569367B2 (en) 2004-11-16 2013-10-29 Allergan, Inc. Ophthalmic compositions and methods for treating eyes
US20070021439A1 (en) * 2005-07-25 2007-01-25 Parion Sciences, Inc. Methods of reducing risk of infection from pathogens with soluble amide and ester pyrazinoylguanidine sodium channel blockers
US7807834B2 (en) * 2005-08-03 2010-10-05 Parion Sciences, Inc. Capped pyrazinoylguanidine sodium channel blockers
GB0520405D0 (en) * 2005-10-07 2005-11-16 Imp College Innovations Ltd Biological agents and method
WO2007070509A2 (en) * 2005-12-13 2007-06-21 University Of Pittsburgh-Of The Commonwealth System Of Higher Education Epithelial sodium channel inhibiting agents and uses therefor
CA2653773A1 (en) * 2006-06-09 2007-12-21 Parion Sciences, Inc. Cyclic substituted pyrazinoylguanidine sodium channel blockers possessing beta agonist activity
US8324218B2 (en) * 2006-06-09 2012-12-04 Parion Sciences, Inc. Aliphatic pyrazinoylguanidine sodium channel blockers with beta agonist activity
ES2392999T3 (es) * 2006-06-09 2012-12-17 Parion Sciences, Inc. Bloqueadores de canales de sodio pirazinoilguanidina sustituida con fenilo que tienen actividad agonista beta
AR062742A1 (es) * 2006-09-07 2008-12-03 Johnson Michael R Hidratacion de la mucosa y depuracion de la mucosa aumentadas por tratamiento con bloquadores de canales de sodio y osmolitos
BRPI0716884A2 (pt) * 2006-09-07 2013-10-15 Parion Sciences Inc Método de intensificação de hidratação mucosal e clearance mucosal através de tratamento com bloqueadores do canal de sódio e osmolitos
GB2447298A (en) * 2007-03-09 2008-09-10 Geraldine Carter Toothpaste containing chromium
US8288391B2 (en) * 2007-04-03 2012-10-16 Parion Sciences, Inc. Pyrazinoylguanidine compounds for use as taste modulators
US20080293740A1 (en) * 2007-04-03 2008-11-27 Parion Sciences, Inc. Method of treating acid-sensing ion channel mediated pain, cough suppression, and central nervous system disorders
CA2702094C (en) 2007-10-10 2018-05-01 Parion Sciences, Inc. Delivering osmolytes by nasal cannula
MX344703B (es) 2008-02-26 2017-01-03 Parion Sciences Inc Bloqueadores de canal de sodio poliaromaticos.
US20100074881A1 (en) * 2008-07-11 2010-03-25 Parion Sciences, Inc. Multiple nebulizer systems
US8945605B2 (en) 2011-06-07 2015-02-03 Parion Sciences, Inc. Aerosol delivery systems, compositions and methods
CN103732213A (zh) 2011-06-07 2014-04-16 帕里昂科学公司 治疗方法
BR112013032771B1 (pt) 2011-06-27 2021-01-12 Parion Sciences, Inc. dipeptídio quimicamente e metabolicamente estável possuindo potente atividade bloqueadora de canais de sódio
AR086745A1 (es) 2011-06-27 2014-01-22 Parion Sciences Inc 3,5-diamino-6-cloro-n-(n-(4-(4-(2-(hexil(2,3,4,5,6-pentahidroxihexil)amino)etoxi)fenil)butil)carbamimidoil)pirazina-2-carboxamida
US9907826B2 (en) 2011-12-07 2018-03-06 Allergan, Inc. Efficient lipid delivery to human tear film using a salt-sensitive emulsion system
SG11201407867VA (en) 2012-05-29 2014-12-30 Parion Sciences Inc Dendrimer like amino amides possessing sodium channel blocker activity for the treatment of dry eye and other mucosal diseases
MX2015007797A (es) 2012-12-17 2015-10-05 Parion Sciences Inc Compuestos de 3,5-diamino-6-cloro-n-(n-(4-fenilbutil) carbamimidoil) pirazin-2-carboxamida.
RU2015129065A (ru) 2012-12-17 2017-01-25 Пэрион Сайенсиз, Инк. Производные хлор-пиразинкарбоксамида, обладающие активностью блокирования эпителиальных натриевых каналов
CA2896686A1 (en) 2012-12-17 2014-06-26 Parion Sciences, Inc. 3,5-diamino-6-chloro-n-(n-(4-phenylbutyl)carbamimidoyl) pyrazine-2- carboxamide compounds
WO2015003083A1 (en) 2013-07-02 2015-01-08 The California Institute For Biomedical Research Compounds for treatment of cystic fibrosis
BR112016003481A2 (pt) 2013-08-23 2020-03-03 Parion Sciences, Inc. Agentes mucolíticos de ditiol
US9102633B2 (en) 2013-12-13 2015-08-11 Parion Sciences, Inc. Arylalkyl- and aryloxyalkyl-substituted epithelial sodium channel blocking compounds
US20150376145A1 (en) 2014-06-30 2015-12-31 Parion Sciences, Inc. Stable sodium channel blockers
WO2016112120A1 (en) * 2015-01-07 2016-07-14 The California Institute For Biomedical Research Compounds for treatment of cystic fibrosis
AU2016211440B2 (en) 2015-01-30 2020-08-27 Parion Sciences, Inc. Novel monothiol mucolytic agents
EP3244893A4 (de) * 2015-02-18 2019-01-09 Parion Sciences, Inc. Natriumkanalblocker für hauterkrankungen
AU2016255851A1 (en) 2015-04-30 2017-12-14 Parion Sciences, Inc. Novel prodrugs of dithiol mucolytic agents
GB201610854D0 (en) 2016-06-21 2016-08-03 Entpr Therapeutics Ltd Compounds
GB201619694D0 (en) 2016-11-22 2017-01-04 Entpr Therapeutics Ltd Compounds
GB201717051D0 (en) 2017-10-17 2017-11-29 Enterprise Therapeutics Ltd Compounds
GB201808093D0 (en) 2018-05-18 2018-07-04 Enterprise Therapeutics Ltd Compounds

Family Cites Families (70)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US397686A (en) * 1889-02-12 Scale for surface measurements
US386401A (en) * 1888-07-17 heady
US2987091A (en) * 1957-08-08 1961-06-06 Cincinnati Mine Machinery Co Set screw construction
BE639386A (de) 1962-10-30
DE1903999U (de) * 1964-04-02 1964-11-05 Jon Martin Jonsson Befestigungsvorrichtung fuer einen bidetzusatz an wasserklosetts.
US3472848A (en) 1966-11-17 1969-10-14 Merck & Co Inc 3-hydroxy and 3-mercapto-pyrazinoyl-guanidines,corresponding ethers and thioethers and processes for their preparation
US3625950A (en) 1968-07-03 1971-12-07 Merck & Co Inc Certain halophenoxy alkanamides, hydrazides and derivatives thereof
US3539569A (en) * 1968-08-21 1970-11-10 Merck & Co Inc Preparation of pyrazinoylguanidines from pyrazinoylureas
US3544571A (en) 1968-09-04 1970-12-01 Merck & Co Inc Process for making pyrazinoylthiourea compounds
US3668241A (en) 1968-11-25 1972-06-06 Merck & Co Inc Substituted 1-oxoinden-5-yloxy alkanoic acids
US3573306A (en) * 1969-03-05 1971-03-30 Merck & Co Inc Process for preparation of n-substituted 3,5-diamino-6-halopyrazinamides
US3684552A (en) * 1970-11-16 1972-08-15 Minnesota Mining & Mfg Heat-sensitive sheet material
US3864401A (en) 1970-12-23 1975-02-04 Merck & Co Inc Substituted 2-aminomethyl-4,6-dihalophenols
US3794734A (en) 1971-03-03 1974-02-26 Merck & Co Inc Methods of treating edema and hypertension using certain 2-aminoethylphenols
US3953476A (en) 1971-12-27 1976-04-27 Merck & Co., Inc. 3-Amino-5-sulfonylbenzoic acids
US3984465A (en) 1972-10-13 1976-10-05 Merck & Co., Inc. 1-Oxo-2,2-disubstituted-5-indanyloxy(or thio)alkanoic acids
US3976686A (en) 1972-10-13 1976-08-24 Merck & Co., Inc. [1-Oxo-2,3-hydrocarbylene-5-indanyloxy(or thio)]alkanoic acids
US4085219A (en) 1972-10-13 1978-04-18 Merck & Co., Inc. 1-Oxo-2,2-disubstituted-5-indanyloxy(or thio)alkanoic acids
US3928324A (en) * 1973-02-08 1975-12-23 Pfizer Malonyl derivatives of 6-({60 -aminoacylamido)penicillanic acids
US3987091A (en) 1973-04-12 1976-10-19 Merck & Co., Inc. 11,12-secoprostaglandins
US3894065A (en) 1973-04-27 1975-07-08 Merck & Co Inc Aryl-oxo-alkanoic acids
US4177285A (en) 1973-10-11 1979-12-04 Merck & Co., Inc. [1-Oxo-2-thienyl-2-substituted-5-indanyloxy (or thio)]alkanoic acids and derivatives thereof
US4006180A (en) 1973-10-12 1977-02-01 Merck & Co., Inc. [1,3-Dihydroxy-2-substituted and 2,2-disubstituted-indanyloxy(or thio)]alkanoic acids
US4012524A (en) 1973-10-12 1977-03-15 Merck & Co., Inc. [1-Hydroxy-5-indanyloxy (or thio)]-alkanoic acids
US3966966A (en) 1973-10-12 1976-06-29 Merck & Co., Inc. Pharmaceutical compositions and method of treatment employing 1,3-dioxo-2,2-disubstituted indanyloxy alkanoic acids
US3976681A (en) 1973-10-12 1976-08-24 Merck & Co., Inc. [1,3-Dioxo-2-substituted and 2,2-disubstituted- indanyloxy (or thio] alkanoic acids
US3929872A (en) 1973-10-12 1975-12-30 Merck & Co Inc Indanacetic acid compounds
US4003927A (en) 1973-10-12 1977-01-18 Merck & Co., Inc. (1-Oxo-7,8-disubstituted-1,2,3,4-tetrahydro-6-naphthyloxy)- and (3,4-disubstituted-5-oxo-6,7,8,9-tetrahydro-5H-benzocycloheptene-2-yloxy) acetic acids and derivatives
US3989749A (en) 1973-10-17 1976-11-02 Merck & Co., Inc. 11,12-Secoprostaglandins
US3991087A (en) 1973-12-13 1976-11-09 Merck & Co., Inc. 8-Halo-11,12-secoprostaglandins
US3979361A (en) 1974-02-20 1976-09-07 Merck & Co., Inc. 2-Aminomethyl-6-trihalo-methylphenols
US3914253A (en) 1974-03-04 1975-10-21 Merck & Co Inc 5-Oxo-6-substituted-cyclopent-{8 f{9 -indole-2-carboxylic acids
US3931239A (en) 1974-04-03 1976-01-06 Merck & Co., Inc. 6-Oxo-7-substituted-6H-indeno-[5,4-b]furan(and thiophene)-carboxylic acids
US3958004A (en) 1974-04-23 1976-05-18 Merck & Co., Inc. Phenoxyacetic acid derivatives as uricosuric agents
US3928624A (en) 1974-04-25 1975-12-23 Merck & Co Inc Phenol compounds in treating pain, fever and inflammation
US3956374A (en) 1974-05-03 1976-05-11 Merck & Co., Inc. Aryl-oxo-heptenoic acids
US3974212A (en) 1974-05-22 1976-08-10 Merck & Co., Inc. [1-Hydroximino-2,2-disubstituted-5-indanyloxy-(or thio)]alkanoic acids
US3991106A (en) 1974-09-13 1976-11-09 Merck & Co., Inc. 16-Ethers of 8-aza-9-dioxothia-11,12-seco-prostaglandins
US3984552A (en) 1975-02-24 1976-10-05 Merck & Co., Inc. 6-Oxo-7-substituted and 7,7-disubstituted-6H-indeno-[5,4-b]furan (and thiophene) carboxylic acids
US4092414A (en) 1975-04-25 1978-05-30 Merck & Co., Inc. 3,4-Dihydrospiro-2H-1,3-benzoxazines and their use in treating edema, abnormal electrolyte retention, and inflammation
US4296122A (en) 1975-07-09 1981-10-20 Merck & Co., Inc. 2,3-Dihydro-6,7-disubstituted-5-(acyl)benzofuran-2-carboxylic acids
US4181727A (en) 1975-07-09 1980-01-01 Merck & Co., Inc. 2,3-Dihydro-6,7-disubstituted-5-acyl benzofuran-2-carboxylic acids
US4087542A (en) 1975-07-09 1978-05-02 Merck & Co., Inc. 2,3-Dihydro-6,7-disubstituted-5-acyl benzofuran-2-carboxylic acids
US4100394A (en) * 1975-12-12 1978-07-11 Adams Industries, Inc. Electric water heater and hot water dispenser
US4085211A (en) 1975-12-15 1978-04-18 Merck & Co., Inc. Pyrazinecarboxamides and processes for preparing same
US4025292A (en) * 1975-12-15 1977-05-24 Bailey A Preston High pressure burner with integral pilot
US4025625A (en) 1976-06-15 1977-05-24 Merck & Co., Inc. Imidazothiazines
US4087526A (en) 1976-07-23 1978-05-02 Merck & Co., Inc. (3-Amino-5-substituted-6-fluoropyrazinoyl or pyrazamido)-guanidines and their derivatives bearing substituents on the guanidino nitrogens
US4067980A (en) 1976-08-16 1978-01-10 Merck & Co., Inc. Spirobenzoxazinium salts, method of use and compositions thereof as antihypertensive agents
US4085117A (en) 1976-10-18 1978-04-18 Merck & Co., Inc. 6,7-Disubstituted-5-(acyl)benzofuran-2-carboxylic acids
US4100294A (en) 1976-12-06 1978-07-11 Merck & Co., Inc. 5-(Hydroxy (substituted) methyl)-2,3-dihydrobenzo furan-2-carboxylic acid and its derivatives
US4105769A (en) 1977-01-24 1978-08-08 Merck & Co., Inc. Inhibition of indoleamine-N-methyl transferase by 2-iminopyridines
US4196292A (en) 1977-06-29 1980-04-01 Merck & Co., Inc. 6-Substituted amiloride derivatives
US4140776A (en) 1977-09-16 1979-02-20 Merck & Co., Inc. N-pyrazinecarbonyl-N'-acylguanidines
US4159279A (en) 1977-11-23 1979-06-26 Merck & Co., Inc. Nuclear substituted 2-hydroxyphenylmethanesulfamic acids
US4145551A (en) 1978-01-09 1979-03-20 Merck & Co., Inc. Pyrazine-2-carbonyloxyguanidines
US4401669A (en) 1978-01-27 1983-08-30 Merck & Co., Inc. 2,3-Dihydro-substituted-5-benzoyl benzofuran-2-carboxylic acids and their use in treating hypertension
US4163781A (en) 1978-04-17 1979-08-07 Merck & Co., Inc. 3-Amino-N-[(phosphonoamino)iminomethyl]-6-halopyrazinecarboxamide compounds, compositions and methods of use
US4246406A (en) 1979-03-27 1981-01-20 Merck & Co., Inc. Heterocyclic substituted pyrazinoylguanidines
US4237144A (en) 1979-06-21 1980-12-02 Merck & Co., Inc. 2,3-Dihydro-2,6,7-trisubstituted-5-acylbenzofurans
US4237130A (en) 1979-06-21 1980-12-02 Merck & Co., Inc. 2,3-Dihydro-6,7-disubstituted-5-(substituted sulfonyl)benzofuran-2-carboxylic acids
US4291050A (en) 1979-06-21 1981-09-22 Merck & Co., Inc. 6,7-Disubstituted-2 or 2,2-substituted-5-substituted-1-indanones
US4298743A (en) 1979-09-11 1981-11-03 Merck & Co., Inc. 4-(Substituted phenyl thiazolyl)-3-hydroxy-3-pyrroline-2,5-diones
US4362724A (en) 1980-05-19 1982-12-07 Merck & Co., Inc. Method of treating edema and hypertension and pharmaceutical composition therefor in which the active ingredient comprises a novel substituted pyrazinyl-1,2,4-oxadiazole and a kaliuretic diuretic
US4317822A (en) 1980-07-02 1982-03-02 Merck & Co., Inc. 3-Amino-5-substituted-6-halo-N-(3,4-dihydro-6-substituted-1,3,5-triazin-2-yl)2-pyrazinecarboxamides
US4277602A (en) 1980-07-02 1981-07-07 Merck & Co., Inc. 3-Amino-5-substituted-6-halo-N-(3,4-dihydro-6-substituted-1,3,5-truazin-2-yl)2-pyrazinecarboxamides
MXPA02000684A (es) * 1999-07-19 2003-07-21 Univ North Carolina Conjugados de bloqueadores del canal de sodio y metodos de uso de los mismos.
US6858615B2 (en) * 2002-02-19 2005-02-22 Parion Sciences, Inc. Phenyl guanidine sodium channel blockers
US6858614B2 (en) * 2002-02-19 2005-02-22 Parion Sciences, Inc. Phenolic guanidine sodium channel blockers
US6903105B2 (en) * 2003-02-19 2005-06-07 Parion Sciences, Inc. Sodium channel blockers

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WO2003070184A3 (en) 2004-06-17
US7247636B2 (en) 2007-07-24
US20040198744A1 (en) 2004-10-07
DE60317884D1 (de) 2008-01-17
US6858614B2 (en) 2005-02-22
EP1485359B1 (de) 2007-12-05
US7192958B2 (en) 2007-03-20
PT1485359E (pt) 2008-03-17
CY1107228T1 (el) 2012-11-21
HK1068609A1 (en) 2005-04-29
US20040198747A1 (en) 2004-10-07
US20030195160A1 (en) 2003-10-16
JP2005526726A (ja) 2005-09-08
DK1485359T3 (da) 2008-04-14
EP1485359A2 (de) 2004-12-15
ES2298505T3 (es) 2008-05-16
KR20040091065A (ko) 2004-10-27
WO2003070184A2 (en) 2003-08-28
US20040198745A1 (en) 2004-10-07
US7368450B2 (en) 2008-05-06
US20040198746A1 (en) 2004-10-07
US7241766B2 (en) 2007-07-10
DE60317884T2 (de) 2009-01-02
US20040204424A1 (en) 2004-10-14
CA2476837A1 (en) 2003-08-28
ATE380181T1 (de) 2007-12-15
US7192959B2 (en) 2007-03-20
EP1485359A4 (de) 2006-03-22

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