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WO1996004905A1 - Derives de l'acide phenoxyphenylacetique - Google Patents

Derives de l'acide phenoxyphenylacetique Download PDF

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Publication number
WO1996004905A1
WO1996004905A1 PCT/US1995/009967 US9509967W WO9604905A1 WO 1996004905 A1 WO1996004905 A1 WO 1996004905A1 US 9509967 W US9509967 W US 9509967W WO 9604905 A1 WO9604905 A1 WO 9604905A1
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WO
WIPO (PCT)
Prior art keywords
propylphenoxy
iso
alkyl
propylbenzenesulfonyl
acetamide
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.)
Ceased
Application number
PCT/US1995/009967
Other languages
English (en)
Inventor
Scott W. Bagley
Theodore P. Broten
Prasun K. Chakravarty
Daljit S. Dhanoa
Kenneth J. Fitch
William J. Greenlee
Nancy Jo Kevin
Gerard R. Kieczykowski
Jay M. Matthews
Douglas J. Pettibone
Ralph A. Rivero
James R. Tata
Thomas F. Walsh
David L. Willams, Jr.
Richard B. Toupence
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck and Co Inc
Original Assignee
Merck and Co 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
Publication date
Priority claimed from US08/294,232 external-priority patent/US5565485A/en
Application filed by Merck and Co Inc filed Critical Merck and Co Inc
Priority to AU32767/95A priority Critical patent/AU705881B2/en
Priority to JP8507425A priority patent/JPH10503779A/ja
Priority to EP95929396A priority patent/EP0774965A4/fr
Publication of WO1996004905A1 publication Critical patent/WO1996004905A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory 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
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/08—Vasodilators for multiple indications
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C65/21—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing ether groups, groups, groups, or groups
    • C07C65/24—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing ether groups, groups, groups, or groups polycyclic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
    • C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
    • C07D317/60—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • This invention is concerned with non-peptidic endothelin receptor antagonists represented by the compound of Formula I, pharmaceutical compositions containing these compounds, as well as combination therapies which include a compound of the present invention.
  • the compounds of the present invention are therapeutic agents particularly useful for the treatment of asthma, hypertension, pulmonary hypertension, arteriosclerosis, congestive heart failure, renal failure, particularly post-ischemic renal failure, cyclosporin
  • nephrotoxicity nephrotoxicity, vasospasm, vascular restenosis, cerebral and cardiac ischemia and other ischemic states, myocardial infarction, Raynaud's disease, benign prostatic hyperplasia, inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, as well as other inflammatory diseases, or endotoxic shock caused by or associated with endothelin.
  • This invention further constitutes a method for antagonizing endothelin receptors in a mammal, including humans, which comprises administering to a mammal in need of such treatment an effective amount of a compound of Formula I.
  • Endothelin is a 21-amino acid peptide produced by endothelial cells.
  • the peptide is secreted not only by endothelial cells but also by tracheal epithelial cells or from kidney cells.
  • Endothelin (ET-1) has a potent vasoconstrictor effect. The vasoconstricting effect is caused by the binding of endothelin to its receptor on the vascular smooth muscle cells.
  • Endothelin- 1 is one of three recently identified potent vasoconstricting peptides which also includes endothelin-2 (ET-2) and endothelin-3 (ET-3) whose sequences differ from ET-1 by two and six amino acids, respectively. 4
  • Increased levels of endothelin are found in the blood of patients with essential hypertension, acute myocardial infarction, pulmonary hypertension, Raynaud's disease or atherosclerosis or in the washing fluids of the respiratory tract of patients with asthma compared to normal levels.
  • Endothelin was also found to control the release of many physiological substances such as renin, atrial natriuretic peptide, endothelium-derived relaxing factor (EDRF), thromboxane A 2 , 14, prostacyclin, norepinephrine, angiotensin II and substance P. 1 1 - 16 Further, endothelin causes contraction of the smooth muscle of the gastrointestinal tract and the uterine smooth muscle. 17 -19 Endothelin has also been shown to promote the growth of rat vascular smooth muscle cells which would suggest a possible relevance to arterial hypertrophy. 20
  • EDRF endothelium-derived relaxing factor
  • Endothelin receptors are present in high concentration in the peripheral tissues and also in the central nervous system, and cerebral administration of endothelin has been shown to induce behavioral changes in animals, suggesting that endothelin may play an important role in controlling neural functions.
  • Endotoxin has been shown to promote the release of endothelin. This finding has suggested that endothelin is an important mediator for endotoxin-induced diseases. 22-23
  • Endothelin is an endogenous substance which directly or indirectly (through the controlled release of various other endogenous substances) induces sustained contraction of vascular or non-vascular smooth muscles. Its excess production or excess secretion is believed to be one of the factors responsible for hypertension, pulmonary
  • Substances which specifically inhibit the binding of endothelin to its receptor are believed to block the physiological effects of endothelin and are useful in treating patients with endothelin related disorders.
  • novel compounds of the present invention are useful as a non-peptidic endothelin antagonists, and have not been disclosed in any issued patents or published patent applications.
  • published patent applications disclosing linear and cyclic peptidic compounds as endothelin antagonists are the following: Fujisawa in European Patent Application EP-457,195 and Patent Cooperation Treaty (PCT) International Application No. WO 93/10144, Banyu in EP-436,189 and 460,679, Immunopharmaceutics Inc. in WO 93/225580, Warner Lambert Co. WO 92/20706 and Takeda Chemical Ind. in EP-528,312, EP-543,425, EP-547,317 and WO 91/13089 .
  • Fujisawa has also disclosed two nonpeptidic endothelin antagonist compounds: anthraquinone derivatives produced by a fermentation process using Streptomyces sp. No. 89009 in EP-405,421 and U.S. Patent No. 5,187,195; and a 4-phenoxyphenol derivative produced by a fermentation process using Penicillium citreonigrum F- 12880 in a UK Patent Application GB 2259450.
  • Shionogi and Co. has also disclosed nonpeptidic endothelin antagonist triterpene compounds which were produced by a fermentation process using Myrica cerifera in WO 92/12991.
  • non-peptidic endothelin antagonist compounds which are known in the patent literature are: 1) a series of substituted ( 1 ,4-quinolinoxy)methylbiphenylcarboxylic acids disclosed by Roussel- Uclaf in EP-498,723; 2) a series of of N-(4-pyrimidinyl)benzene- sulfonamides with different substitution patterns from Hoffmann-La Roche published in EP-510,526, EP-526,708 and EP-601,386; 3) a series of naphthalenesulfonamides and benzene sulfonamides disclosed by E.R.
  • This invention is concerned with novel compounds of structural formula I :
  • R 1 , R 2 , R 3a and R 3b are independently
  • R 1 and R 2 on adjacent carbon atoms can be joined together to form a ring structure:
  • A represents:
  • Y is -O-, -S(O) n - and NR 7 ;
  • R 4 and R-5 are independently:
  • R 7 is :
  • R 8 is :
  • R 9 and R 10 are independently:
  • R 9 and R 10 on adjacent carbons can join together to form a fused phenyl ring, unsubstituted or substituted with a substituent selected from the group consisting of: (C 1 -C 6 )alkyl, (C 1 - C 6 )-alkoxy, (C 3 -C 7 )-cycloalkyl and (C 1 -C 6 )-alkyl-(C 3 -
  • R 1 1 is
  • aryl wherein aryl is defined as phenyl or
  • naphthyl which is unsubstituted or substituted with one or two substituents selected from the group consisting of:
  • R 12 is
  • amino acid is defined as an L-or D- amino acid selected from the group consisting of Ala, He, Phe, Asp, Pro and Val and which can be further substituted as a (C 1 -C 6 )- alkyl ester or an amide, or
  • aryl is defined as phenyl or naphthyl which is unsubstituted or substituted with one, two or three substituents selected from the group consisting of:
  • heteroaryl is defined as carbazolyl, furyl, thienyl, pyrrolyl, isothiazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrazolyl, pyrazinyl, pyridyl,
  • pyrimidyl purinyl or quinolinyl, which is unsubstituted or substituted with one, two or three substituents selected from the group consisting of: i) (C 1 -C 4 )-alkyl,
  • R 14 and R 15 independently are (C 1 -C 6 -alkyl or phenyl
  • R 16 is H, (C 1 -C 6 )-alkyl or (C 1 -C 6 )-alkylphenyl.
  • R 1 , R 2 , R 3a and R 3b are independently:
  • A represents:
  • R 8 is:
  • R 9 and R 10 are independently:
  • R 9 and R 10 on adjacent carbons can join together to form a fused phenyl ring, unsubstituted or substituted with a substituent selected from the group consisting of: (C 1 -C 6 )alkyl , (C 1 -
  • R 1 1 is
  • aryl wherein aryl is defined as phenyl or
  • naphthyl which is unsubstituted or substituted with one or two substituents selected from the group consisting of:
  • R 12 is
  • amino acid is defined as an L-or D- amino acid selected from the group consisting of Ala, Ile, Phe, Asp, Pro and Val and which can be further substituted as a (C 1 -C 6 )- alkyl ester or an amide, or
  • phenyl or naphthyl which is unsubstituted or substituted with one, two or three substituents selected from the group consisting of: i) (C 1 -C 4 )-alkyl,
  • heteroaryl is defined as carbazolyl, furyl, thienyl, pyrrolyl, isothiazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrazolyl, pyrazinyl, pyridyl,
  • pyrimidyl purinyl or quinolinyl, which is unsubstituted or substituted with one, two or three substituents selected from the group consisting of: i) (C 1 -C 4 )-alkyl,
  • R 13 is:
  • R 14 and R 15 independently are (C 1 -C 6 )alkyl or phenyl
  • R 16 is H, (C 1 -C 6 )-alkyl, or (C 1 -C 6 )-alkylphenyl.
  • R 1 , R 2 , R 3a and R 3b are independently:
  • A represents:
  • Y is -O-, -S- and NR 7 R 4 and R 5 are independently:
  • R 8 is:
  • R 9 and R 10 are independently:
  • aryl wherein aryl is defined as phenyl or
  • naphthyl which is unsubstituted or substituted with one or two substituents selected from the group consisting of:
  • Q is O, S or -NR 7 ;
  • R 12 is
  • alkyl is defined as unsubstituted or substituted with one or two substituents selected from the group consisting of: i) -OH,
  • amino acid is defined as an L-or D- amino acid selected from the group consisting of Ala, Ile, Phe, Asp, Pro and Val and which can be further substituted as a (C 1 -C 6 )- alkyl ester or an amide, or
  • aryl is defined as phenyl or naphthyl which is unsubstituted or substituted with one, two or three substituents selected from the group consisting of:
  • heteroaryl is defined as carbazolyl, furyl, thienyl, pyrrolyl, isothiazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrazolyl, pyrazinyl, pyridyl, pyrimidyl, purinyl, or quinolinyl, which is unsubstituted or substituted with one, two or three substituents selected from the group consisting of: i) (C 1 -C 4 )-alkyl,
  • R 13 is: (C 1 -C 4 )-alkyl
  • R 16 is H, (C 1 -C 6 )-alkyl, or (C 1 -C 6 )-alkylphenyl.
  • a subclass of the compounds of Formula III are the compounds of Formula IV:
  • A represents:
  • Y is -O-
  • R 3a is:
  • R 6 is:
  • R 8 is:
  • R 9 is:
  • aryl wherein aryl is defined as phenyl or
  • naphthyl which is unsubstituted or substituted with one or two substituents selected from the group consisting of:
  • Q is O, S or -NR 7 ;
  • R 12 is
  • amino acid is defined as an L-or D- amino acid selected from the group consisting of Ala, He, Phe, Asp, Pro and Val and which can be further substituted as a (C 1 -C 6 )- alkyl ester or an amide, or (m)
  • aryl is defined as phenyl or naphthyl which is unsubstituted or substituted with one, two or three substituents selected from the group consisting of:
  • heteroaryl is defined as carbazolyl, furyl, thienyl, pyrrolyl, isothiazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrazolyl, pyrazinyl, pyridyl, pyrimidyl, purinyl, or quinolinyl, which is unsubstituted or substituted with one, two, or three substituents selected from the group consisting of:
  • R 13 is: (C 1 -C 4 )-alkyl
  • R 16 is H, (C 1 -C 6 )-alkyl, or (C 1 -C 6 )-alkylphenyl.
  • R 1 , R 2 , R 3a and R 3b are independently:
  • R 8 is:
  • R 9 and R 10 are independently:
  • aryl wherein aryl is defined as phenyl or
  • naphthyl which is unsubstituted or substituted with one or two substituents selected from the group consisting of:
  • Q is O, S or -NR 7 ;
  • R 12 is
  • amino acid is defined as an L-or D- amino acid selected from the group consisting of Ala, He, Phe, Asp, Pro and Val and which can be further substituted as a (C 1 -C 6 )- alkyl ester or an amide, or
  • phenyl or naphthyl which is unsubstituted or substituted with one, two or three substituents selected from the group consisting of: i) (C 1 -C 4 )-alkyl,
  • R 4 (b) unsubstituted or substituted as defined in R 4 (b), (g) -CONHSO 2 -heteroaryl, wherein heteroaryl is defined as carbazolyl, furyl, thienyl, pyrrolyl, isothiazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrazolyl, pyrazinyl, pyridyl,
  • R 13 is: (C 1 -C 4 )-alkyl
  • R 16 is H, (C 1 -C 6 )-alkyl, or (C 1 -C 6 )-alkylphenyl.
  • R 1 and R 2 are represented by the following ring structure:
  • A represents:
  • R 3a and R 3b are independently:
  • R 8 is:
  • R 9 and R 10 are independently:
  • aryl wherein aryl is defined as phenyl or
  • naphthyl which is unsubstituted or substituted with one or two substituents selected from the group consisting of:
  • Q is O, S or -NR 7 ;
  • R 12 is
  • amino acid is defined as an L-or D- amino acid selected from the group consisting of Ala, Ile, Phe, Asp, Pro and Val and which can be further substituted as a (C 1 -C 6 )- alkyl ester or an amide, or
  • phenyl or naphthyl which is unsubstituted or substituted with one, two or three substituents selected from the group consisting of: i) (C 1 -C 4 )-alkyl,
  • heteroaryl is defined as carbazolyl, furyl, thienyl, pyrrolyl, isothiazolyl, imidazolyl, isoxazolyl, thiazolyl, oxazolyl, pyrazolyl, pyrazinyl, pyridyl,
  • R 13 is: (C 1 -C 4 )-alkyl
  • R 16 is H, (C 1 -C 6 )-alkyl, or (C 1 -C 6 )-alkylphenyl.

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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
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  • Reproductive Health (AREA)
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Abstract

Acide phénoxyphénylacétique et ses dérivés de formule générale (I) présentant une activité antagoniste de l'endothéline, et s'avérant utiles dans le traitement des troubles cardio-vasculaires tels que l'hypertension, l'insuffisance rénale postischémique, les angiospasmes, les ischémies cérébrales et coronarienne, l'infarctus du myocarde, le choc endotoxique, l'adénome prostatique, certains troubles inflammatoires dont la maladie de Raynaud et l'asthme.
PCT/US1995/009967 1993-03-19 1995-08-07 Derives de l'acide phenoxyphenylacetique Ceased WO1996004905A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
AU32767/95A AU705881B2 (en) 1993-03-19 1995-08-07 Phenoxyphenylacetic acid derivatives
JP8507425A JPH10503779A (ja) 1994-08-08 1995-08-07 フェノキシフェニル酢酸誘導体
EP95929396A EP0774965A4 (fr) 1994-08-08 1995-08-07 Derives de l'acide phenoxyphenylacetique

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US28737494A 1994-08-08 1994-08-08
US08/294,232 US5565485A (en) 1993-03-19 1994-08-22 Biphenyl compounds useful or endothelin antagonists
US47317295A 1995-06-07 1995-06-07
US287,374 1995-06-07
US473,172 1995-06-07
US294,232 1995-06-07

Publications (1)

Publication Number Publication Date
WO1996004905A1 true WO1996004905A1 (fr) 1996-02-22

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PCT/US1995/009967 Ceased WO1996004905A1 (fr) 1993-03-19 1995-08-07 Derives de l'acide phenoxyphenylacetique

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EP (1) EP0774965A4 (fr)
JP (1) JPH10503779A (fr)
CA (1) CA2195758A1 (fr)
WO (1) WO1996004905A1 (fr)

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997021700A1 (fr) * 1995-12-12 1997-06-19 Merck & Co., Inc. Procede relatif a la fabrication d'un antagoniste de l'endotheline
US5688974A (en) * 1995-12-12 1997-11-18 Merck & Co., Inc. Process for the preparation of an endothelin antagonist
WO1999048530A1 (fr) * 1998-03-23 1999-09-30 Merck & Co., Inc. Therapie combinee pour le traitement de l'hyperplasie prostatique benigne
US6410554B1 (en) 1998-03-23 2002-06-25 Merck & Co., Inc. Combination therapy for the treatment of benign prostatic hyperplasia
WO2010137336A1 (fr) * 2009-05-29 2010-12-02 興和株式会社 NOUVEAU DÉRIVÉ D'ACIDE α-PHÉNOXYBENZÈNEACÉTIQUE ET PRÉPARATION PHARMACEUTIQUE LE CONTENANT
US8592629B2 (en) 2010-07-12 2013-11-26 Pfizer Limited Sulfonamide derivatives as Nav 1.7 inhibitors
US8685977B2 (en) 2010-07-12 2014-04-01 Pfizer Limited Chemical compounds
US8772293B2 (en) 2010-07-09 2014-07-08 Pfizer Limited Chemical compounds
US8772343B2 (en) 2010-07-12 2014-07-08 Pfizer Limited Chemical compounds
US9085517B2 (en) 2011-12-15 2015-07-21 Pfizer Limited Sulfonamide derivatives
US9096500B2 (en) 2010-07-12 2015-08-04 Pfizer Limited Acyl sulfonamide compounds
US9102621B2 (en) 2010-07-12 2015-08-11 Pfizer Limited Acyl sulfonamide compounds

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NZ535603A (en) * 2002-03-20 2007-10-26 Metabolex Inc Substituted phenylacetic acids

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5334598A (en) * 1993-03-19 1994-08-02 Merck & Co., Inc. Six-membered ring fused imidazoles substituted with phenoxyphenylacetic acid derivatives

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK0617001T3 (da) * 1993-03-19 2000-04-17 Merck & Co Inc Phenoxyphenyleddikesyrederivater
US5559135A (en) * 1994-09-14 1996-09-24 Merck & Co., Inc. Endothelin antagonists bearing pyridyl amides

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5334598A (en) * 1993-03-19 1994-08-02 Merck & Co., Inc. Six-membered ring fused imidazoles substituted with phenoxyphenylacetic acid derivatives

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
HETEROCYCLES, Volume 30, No. 2, issued 1990, JUNG et al., "Preparation of N-...Lycorine", Compound No. 14, page 84. *
See also references of EP0774965A4 *

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997021700A1 (fr) * 1995-12-12 1997-06-19 Merck & Co., Inc. Procede relatif a la fabrication d'un antagoniste de l'endotheline
US5688974A (en) * 1995-12-12 1997-11-18 Merck & Co., Inc. Process for the preparation of an endothelin antagonist
WO1999048530A1 (fr) * 1998-03-23 1999-09-30 Merck & Co., Inc. Therapie combinee pour le traitement de l'hyperplasie prostatique benigne
US6410554B1 (en) 1998-03-23 2002-06-25 Merck & Co., Inc. Combination therapy for the treatment of benign prostatic hyperplasia
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US8592629B2 (en) 2010-07-12 2013-11-26 Pfizer Limited Sulfonamide derivatives as Nav 1.7 inhibitors
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US8772343B2 (en) 2010-07-12 2014-07-08 Pfizer Limited Chemical compounds
US9096500B2 (en) 2010-07-12 2015-08-04 Pfizer Limited Acyl sulfonamide compounds
US9102621B2 (en) 2010-07-12 2015-08-11 Pfizer Limited Acyl sulfonamide compounds
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CA2195758A1 (fr) 1996-02-22
EP0774965A4 (fr) 1997-10-29
EP0774965A1 (fr) 1997-05-28
JPH10503779A (ja) 1998-04-07

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