WO1999006397A3 - Pyrrolidine-3-carboxylic acid derivatives and their use as endothelin antagonists - Google Patents

Pyrrolidine-3-carboxylic acid derivatives and their use as endothelin antagonists Download PDF

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Publication number
WO1999006397A3
WO1999006397A3 PCT/US1998/015479 US9815479W WO9906397A3 WO 1999006397 A3 WO1999006397 A3 WO 1999006397A3 US 9815479 W US9815479 W US 9815479W WO 9906397 A3 WO9906397 A3 WO 9906397A3
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WO
WIPO (PCT)
Prior art keywords
pyrrolidine
carboxylic acid
acid derivatives
endothelin antagonists
endothelin
Prior art date
Application number
PCT/US1998/015479
Other languages
French (fr)
Other versions
WO1999006397A2 (en
Inventor
Martin Winn
Steven A Boyd
Charles W Hutchins
Hwan-Soo Jae
Andrew S Tasker
Thomas W Von Geldern
Jeffrey A Kester
Bryan K Sorensen
Bruce G Szczepankiewicz
Kenneth J Henry
Gang Liu
Steven J Wittenberger
Steven A King
Original Assignee
Abbott Lab
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 US08/905,913 external-priority patent/US6162927A/en
Priority to JP2000505155A priority Critical patent/JP2001512119A/en
Priority to BR9815296-3A priority patent/BR9815296A/en
Priority to IL13417598A priority patent/IL134175A0/en
Priority to CA002297894A priority patent/CA2297894A1/en
Priority to PL98342500A priority patent/PL342500A1/en
Priority to AU85921/98A priority patent/AU748469B2/en
Priority to NZ502395A priority patent/NZ502395A/en
Application filed by Abbott Lab filed Critical Abbott Lab
Priority to EP98937139A priority patent/EP1003740A2/en
Priority to HU0003484A priority patent/HUP0003484A3/en
Priority to SK145-2000A priority patent/SK1452000A3/en
Publication of WO1999006397A2 publication Critical patent/WO1999006397A2/en
Publication of WO1999006397A3 publication Critical patent/WO1999006397A3/en
Priority to NO20000542A priority patent/NO20000542L/en
Priority to BG104216A priority patent/BG104216A/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
    • C07D207/24—Oxygen or sulfur atoms
    • C07D207/26—2-Pyrrolidones
    • C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
    • C07D207/27—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs 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
    • 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
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • 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
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/06—Antimigraine agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • 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
    • 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
    • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no 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
    • C07D207/16—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
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D405/04—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 directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D405/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Urology & Nephrology (AREA)
  • Neurology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Vascular Medicine (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Pain & Pain Management (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Neurosurgery (AREA)
  • Diabetes (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Steroid Compounds (AREA)
  • Pyrrole Compounds (AREA)

Abstract

A compound of formula (I), or a pharmaceutically acceptable salt thereof, is disclosed, as well as processes for and intermediates in the preparation thereof, and a method of antagonizing endothelin.
PCT/US1998/015479 1996-02-13 1998-07-27 Pyrrolidine-3-carboxylic acid derivatives and their use as endothelin antagonists WO1999006397A2 (en)

Priority Applications (12)

Application Number Priority Date Filing Date Title
SK145-2000A SK1452000A3 (en) 1997-08-04 1998-07-27 Pyrrolidine-3-carboxylic acid derivatives and their use as endothelin antagonists
NZ502395A NZ502395A (en) 1997-08-04 1998-07-27 4-Benzodioxolyl substituted pyrrolidine-3-carboxylic acid derivatives useful as endothelin antagonists
IL13417598A IL134175A0 (en) 1997-08-04 1998-07-27 Endothelin antagonists
CA002297894A CA2297894A1 (en) 1997-08-04 1998-07-27 Pyrrolidine-3-carboxylic acid derivatives and their use as endothelin antagonists
PL98342500A PL342500A1 (en) 1997-08-04 1998-07-27 Derivatives of pyrolydin-3-carboxylic acid and their application as endothelin antagonists
AU85921/98A AU748469B2 (en) 1996-02-13 1998-07-27 Endothelin antagonists
EP98937139A EP1003740A2 (en) 1997-08-04 1998-07-27 Pyrrolidine-3-carboxylic acid derivatives and their use as endothelin antagoists
JP2000505155A JP2001512119A (en) 1997-08-04 1998-07-27 Endothelin antagonist
BR9815296-3A BR9815296A (en) 1997-08-04 1998-07-27 Derivatives of 3-pyrrolidine carboxylic acid and use of them as endothelin antagonists
HU0003484A HUP0003484A3 (en) 1997-08-04 1998-07-27 Pyrrolidine-3-crboxylic acid derivatives and their use as endothelin antagonists
NO20000542A NO20000542L (en) 1997-08-04 2000-02-02 Endothelin antagonists
BG104216A BG104216A (en) 1997-08-04 2000-03-02 Derivatives of pyrrolidine-3-carbonic acids and their application as endotheline antagonists

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US08/905,913 US6162927A (en) 1994-08-19 1997-08-04 Endothelin antagonists
US4895598A 1998-03-27 1998-03-27
US09/048,955 1998-03-27
US08/905,913 1998-03-27

Publications (2)

Publication Number Publication Date
WO1999006397A2 WO1999006397A2 (en) 1999-02-11
WO1999006397A3 true WO1999006397A3 (en) 1999-12-09

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PCT/US1998/015479 WO1999006397A2 (en) 1996-02-13 1998-07-27 Pyrrolidine-3-carboxylic acid derivatives and their use as endothelin antagonists

Country Status (16)

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EP (1) EP1003740A2 (en)
JP (1) JP2001512119A (en)
CN (1) CN1301264A (en)
AU (1) AU748469B2 (en)
BG (1) BG104216A (en)
BR (1) BR9815296A (en)
CA (1) CA2297894A1 (en)
HU (1) HUP0003484A3 (en)
IL (1) IL134175A0 (en)
NO (1) NO20000542L (en)
NZ (1) NZ502395A (en)
PL (1) PL342500A1 (en)
SK (1) SK1452000A3 (en)
TR (4) TR200501137T2 (en)
TW (1) TW552260B (en)
WO (1) WO1999006397A2 (en)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
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CA2337230A1 (en) * 1998-07-15 2000-01-27 Bristol-Myers Squibb Company Stereoselective reductive amination of ketones
TWI306760B (en) 2000-08-07 2009-03-01 Abbott Lab Use of an endothelin et-a receptor antagonist and orally delivered pharmaceutical composition comprising the same
WO2002051836A1 (en) * 2000-12-27 2002-07-04 Kyowa Hakko Kogyo Co., Ltd. Dipeptidyl peptidase iv inhibitor
CN1514727A (en) * 2001-04-11 2004-07-21 ���Ͽع����޹�˾ Favorable modulation of health-related quality of life and health-related quality-adjusted time-to progression of disease in patients with prostate cancer
FR2874015B1 (en) * 2004-08-05 2006-09-15 Sanofi Synthelabo N- (1H-INDOLYL) -1H-INDOLE-2-CARBOXAMIDE DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC USE
FR2880625B1 (en) * 2005-01-07 2007-03-09 Sanofi Aventis Sa N- (HETEROARYL) -1H-INDOLE-2-CARBOXAMIDE DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC USE
WO2007034406A1 (en) * 2005-09-22 2007-03-29 Actelion Pharmaceuticals Ltd Pyrrolidine-3-carboxylic acid amide derivatives and their use as inhibitors of renin
CA2904447C (en) 2007-08-22 2017-01-03 Abbvie Deutschland Gmbh & Co Kg Therapy for complications of diabetes
WO2011114103A1 (en) 2010-03-18 2011-09-22 Biolipox Ab Pyrimidinones for use as medicaments
JO2998B1 (en) 2010-06-04 2016-09-05 Amgen Inc Piperidinone derivatives as mdm2 inhibitors for the treatment of cancer
JP6093770B2 (en) 2011-09-27 2017-03-08 アムジエン・インコーポレーテツド Heterocyclic compounds as MDM2 inhibitors for the treatment of cancer
WO2013082458A1 (en) 2011-12-02 2013-06-06 The Regents Of The University Of California Reperfusion protection solution and uses thereof
US11407721B2 (en) 2013-02-19 2022-08-09 Amgen Inc. CIS-morpholinone and other compounds as MDM2 inhibitors for the treatment of cancer
CA2902856C (en) 2013-02-28 2021-02-16 Amgen Inc. A benzoic acid derivative mdm2 inhibitor for the treatment of cancer
CA2906538C (en) 2013-03-14 2021-02-02 Ana Gonzalez Buenrostro Heteroaryl acid morpholinone compounds as mdm2 inhibitors for the treatment of cancer
JOP20200296A1 (en) 2013-06-10 2017-06-16 Amgen Inc Processes of Making and Crystalline Forms of a MDM2 Inhibitor
CN104262329A (en) * 2014-10-22 2015-01-07 南京友杰医药科技有限公司 Preparation method for anti-form atrasentan
WO2024022262A1 (en) * 2022-07-25 2024-02-01 深圳信立泰药业股份有限公司 Salt of endothelin a (eta) receptor antagonist compound, and preparation method therefor and medical use thereof

Citations (4)

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EP0439444A2 (en) * 1990-01-22 1991-07-31 Monsanto Company Synthesis of chiral pyrrolidine and piperidine glycosidase inhibitors
WO1996006095A1 (en) * 1994-08-19 1996-02-29 Abbott Laboratories Endothelin antagonists
WO1997030046A1 (en) * 1996-02-13 1997-08-21 Abbott Laboratories 4-(benzo-1,3-dioxolyl)-pyrrolidine-3-carboxylic acid derivatives as endothelin antagonists
US5668164A (en) * 1996-07-12 1997-09-16 Abbott Laboratories Process for synthesis of chiral cis-and trans-3-amino-4 substituted pyrrolidine compounds

Patent Citations (4)

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EP0439444A2 (en) * 1990-01-22 1991-07-31 Monsanto Company Synthesis of chiral pyrrolidine and piperidine glycosidase inhibitors
WO1996006095A1 (en) * 1994-08-19 1996-02-29 Abbott Laboratories Endothelin antagonists
WO1997030046A1 (en) * 1996-02-13 1997-08-21 Abbott Laboratories 4-(benzo-1,3-dioxolyl)-pyrrolidine-3-carboxylic acid derivatives as endothelin antagonists
US5668164A (en) * 1996-07-12 1997-09-16 Abbott Laboratories Process for synthesis of chiral cis-and trans-3-amino-4 substituted pyrrolidine compounds

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Title
A. S. TASKER ET. AL.: "Potent and Selective Non-benzodioxole Containing Endothelin A Receptor Antagonists"", JOURNAL OF MEDICINAL CHEMISTRY, vol. 40, no. 3, 31 January 1997 (1997-01-31), pages 322 - 30, XP002082166 *
C. R. CRAIG ET. AL.: "Modern Pharmacology, Third Edition", LITTLE, BROWN AND COMPANY, BOSTON, US, XP002118728 *
H-S JAE ET. AL.: "Pyrrolidine-3-carboxylic Acids as Endothelin Antagonists. 2. Sulfonamide based ETA-ETB Mixed Antagonists.", JOURNAL OF MEDICINAL CHEMISTRY, vol. 40, no. 20, 26 September 1997 (1997-09-26), pages 3217 - 27, XP002082169 *
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M. WINN ET. AL.: "2,4-Diarylpyrrolidine-3-carboxylci Acids- Potent ETA Selective Endothelin Receptor Antagonists. 1. Discovery of A-127722.", JOURNAL OF MEDICINAL CHEMISTRY, vol. 39, no. 5, 1 March 1996 (1996-03-01), pages 1039 - 48, XP002082167 *
S. S. BHAGWAT ET. AL.: "Synthesis of Enantiomerically Pure Pyrrolidinones as Endothelin Receptor Antagonists.", TETRAHEDRON LETTERS, vol. 37, no. 27, 1996, pages 4627 - 30, XP002082168 *

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IL134175A0 (en) 2001-04-30
CA2297894A1 (en) 1999-02-11
CN1301264A (en) 2001-06-27
NZ502395A (en) 2002-08-28
WO1999006397A2 (en) 1999-02-11
HUP0003484A3 (en) 2002-02-28
BG104216A (en) 2000-12-29
TR200000993T2 (en) 2000-12-21
TW552260B (en) 2003-09-11
AU748469B2 (en) 2002-06-06
TR200501137T2 (en) 2005-12-21
HUP0003484A2 (en) 2002-01-28
SK1452000A3 (en) 2001-05-10
NO20000542D0 (en) 2000-02-02
TR200101233T2 (en) 2002-06-21
BR9815296A (en) 2001-11-20
AU8592198A (en) 1999-02-22
PL342500A1 (en) 2001-06-04
EP1003740A2 (en) 2000-05-31
TR200101234T2 (en) 2002-06-21
NO20000542L (en) 2000-04-04
JP2001512119A (en) 2001-08-21

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