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WO1999007731A1 - INHIBITEURS SELECTIFS DU FACTEUR Xa - Google Patents

INHIBITEURS SELECTIFS DU FACTEUR Xa Download PDF

Info

Publication number
WO1999007731A1
WO1999007731A1 PCT/US1998/016705 US9816705W WO9907731A1 WO 1999007731 A1 WO1999007731 A1 WO 1999007731A1 US 9816705 W US9816705 W US 9816705W WO 9907731 A1 WO9907731 A1 WO 9907731A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
alkyl
compound
aryl
alkylaryl
Prior art date
Application number
PCT/US1998/016705
Other languages
English (en)
Inventor
Robert M. Scarborough
Original Assignee
Cor Therapeutics, 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
Application filed by Cor Therapeutics, Inc. filed Critical Cor Therapeutics, Inc.
Priority to JP2000506233A priority Critical patent/JP2001515842A/ja
Priority to EP98939912A priority patent/EP0994894A1/fr
Priority to AU88270/98A priority patent/AU744626B2/en
Priority to CA002299610A priority patent/CA2299610A1/fr
Priority to NZ502876A priority patent/NZ502876A/en
Publication of WO1999007731A1 publication Critical patent/WO1999007731A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06139—Dipeptides with the first amino acid being heterocyclic
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • G is selected from the group consisting of a direct link, C 3 _ 8 cycloalkyl, aryl, and a five to ten membered heterocyclic ring system containing 1 -4 heteroatoms selected from the group consisting of N, O and S;
  • alkyl refers to saturated aliphatic groups including straight-chain, branched-chain, cyclic groups, and combinations thereof, having the number of carbon atoms specified, or if no number is specified, having up to 12 carbon atoms.
  • alkylaryl and alkenylaryl refer to an alkyl group or alkenyl group, respectively, having the number of carbon atoms designated, appended to one, two, or three aryl groups.
  • benzyl refers to -CH -C 6 H 5 .
  • alkyloxy refers to an alkyl group linked to an oxygen atom, such as methoxy, ethoxy, and so forth.
  • halogen refer to Cl, Br, F or I substituents.
  • direct link as used herein refers to a bond directly linking the substituents on each side of the direct link.
  • “Pharmaceutically acceptable acid addition salt” refers to those salts which retain the biological effectiveness and properties of the free bases and which are not biologically or otherwise undesirable, formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like, and organic acids such as acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid and the like.
  • inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like
  • organic acids such as acetic acid, propionic acid, glycolic acid, pyruvic acid
  • K', K", K'" and K"" are -CH-; more preferably K', K", K"' and K"" are all -CH-.
  • R 4 or R 5 is preferably halogen.
  • the invention encompasses compounds of general structural formula VIII, where R , R 2 and R 3 are H; r is 3; s is 0; t is 1 ; A is H; D is phenyl; E is -SO 2 -; G is a direct link; J is
  • Therapeutically effective dosages may be determined by either in vitro or in vivo methods. For each particular compound of the present invention, individual determinations may be made to determine the optimal dosage required.
  • the range of therapeutically effective dosages will be influenced by the route of administration, the therapeutic objectives and the condition of the patient. For injection by hypodermic needle, it may be assumed the dosage is delivered into the body's fluids. For other routes of administration, the absorption efficiency must be individually determined for each compound by methods well known in pharmacology. Accordingly, it may be necessary for the therapist to titer the dosage and modify the route of administration as required to obtain the optimal therapeutic effect.
  • the determination of effective dosage levels that is, the dosage levels necessary to achieve the desired result, will be readily determined by one skilled in the art.
  • the compounds of the invention can be administered orally or parenterally in an effective amount within the dosage range of about 0.1 to 100 mg/kg, preferably about 0.5 to 50 mg/kg and more preferably about 1 to 20 mg/kg on a regimen in a single or 2 to 4 divided daily doses and/or continuous infusion.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Public Health (AREA)
  • Hematology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Diabetes (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)

Abstract

La présente invention concerne de nouveaux composés, ainsi que leurs sels et leurs compositions, efficaces contre le facteur Xa mammalien. Ces composés, représentés par la formule (I), sont utiles in vitro et in vivo pour prévenir ou traiter les troubles de la coagulation.
PCT/US1998/016705 1997-08-11 1998-08-11 INHIBITEURS SELECTIFS DU FACTEUR Xa WO1999007731A1 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
JP2000506233A JP2001515842A (ja) 1997-08-11 1998-08-11 選択的Ｘａ因子阻害剤
EP98939912A EP0994894A1 (fr) 1997-08-11 1998-08-11 INHIBITEURS SELECTIFS DU FACTEUR Xa
AU88270/98A AU744626B2 (en) 1997-08-11 1998-08-11 Selective factor Xa inhibitors
CA002299610A CA2299610A1 (fr) 1997-08-11 1998-08-11 Inhibiteurs selectifs du facteur xa
NZ502876A NZ502876A (en) 1997-08-11 1998-08-11 Fused bicyclic lactam selective factor Xa inhibitors for treating thrombosis related diseases

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US90803197A 1997-08-11 1997-08-11
US8418497P 1997-08-11 1997-08-11
US08/908,031 1997-08-11
US60/084,184 1997-08-11

Publications (1)

Publication Number Publication Date
WO1999007731A1 true WO1999007731A1 (fr) 1999-02-18

Family

ID=26770690

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1998/016705 WO1999007731A1 (fr) 1997-08-11 1998-08-11 INHIBITEURS SELECTIFS DU FACTEUR Xa

Country Status (5)

Country Link
EP (1) EP0994894A1 (fr)
JP (1) JP2001515842A (fr)
CA (1) CA2299610A1 (fr)
NZ (1) NZ502876A (fr)
WO (1) WO1999007731A1 (fr)

Cited By (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6133256A (en) * 1997-04-14 2000-10-17 Cor Therapeutics Inc Selective factor Xa inhibitors
US6194435B1 (en) 1996-10-11 2001-02-27 Cor Therapeutics, Inc. Lactams as selective factor Xa inhibitors
US6204268B1 (en) 1997-04-14 2001-03-20 Cor Therapeutics, Inc Selective factor Xa inhibitors
US6211183B1 (en) 1997-04-14 2001-04-03 Cor Therapeutics, Inc. Selective factor Xa inhibitors
US6218382B1 (en) 1997-08-11 2001-04-17 Cor Therapeutics, Inc Selective factor Xa inhibitors
US6228854B1 (en) 1997-08-11 2001-05-08 Cor Therapeutics, Inc. Selective factor Xa inhibitors
US6262047B1 (en) 1996-10-11 2001-07-17 Cor Therapeutics, Inc. Selective factor Xa inhibitors
US6297233B1 (en) 1999-02-09 2001-10-02 Bristol-Myers Squibb Company Lactam inhibitors of FXa and method
WO2001079261A1 (fr) * 2000-04-14 2001-10-25 Corvas International, Inc. Derives de tetrahydro-azepinone servant d'inhibiteurs de la thrombine
US6333321B1 (en) 1997-08-11 2001-12-25 Cor Therapeutics, Inc. Selective factor Xa inhibitors
US6369080B2 (en) 1996-10-11 2002-04-09 Cor Therapeutics, Inc. Selective factor Xa inhibitors
US6369063B1 (en) 1997-04-14 2002-04-09 Cor Therapeutics, Inc. Selective factor Xa inhibitors
US6469029B1 (en) 1999-09-13 2002-10-22 3-Dimensional Pharmaceuticals, Inc. Azacycloalkanone serine protease inhibitors
US6495540B2 (en) 2000-03-28 2002-12-17 Bristol - Myers Squibb Pharma Company Lactams as inhibitors of A-β protein production
US6503901B1 (en) 1999-10-08 2003-01-07 Bristol Myers Squibb Pharma Company Amino lactam sulfonamides as inhibitors of Aβ protein production
US6503902B2 (en) 1999-09-13 2003-01-07 Bristol-Myers Squibb Pharma Company Hydroxyalkanoylaminolactams and related structures as inhibitors of a β protein production
US6509333B2 (en) 2000-06-01 2003-01-21 Bristol-Myers Squibb Pharma Company Lactams substituted by cyclic succinates as inhibitors of Aβ protein production
US6511973B2 (en) 2000-08-02 2003-01-28 Bristol-Myers Squibb Co. Lactam inhibitors of FXa and method
US6525044B2 (en) 2000-02-17 2003-02-25 Bristol-Myers Squibb Company Succinoylamino carbocycles and heterocycles as inhibitors of a-β protein production
US6525076B1 (en) 1996-10-11 2003-02-25 Millennium Pharmaceuticals, Inc. Selective factor Xa inhibitors
US6713476B2 (en) 2000-04-03 2004-03-30 Dupont Pharmaceuticals Company Substituted cycloalkyls as inhibitors of a beta protein production
US6759404B2 (en) 2000-04-03 2004-07-06 Richard E. Olson Cyclic malonamides as inhibitors of aβ protein production
US6900199B2 (en) 2000-04-11 2005-05-31 Bristol-Myers Squibb Pharma Company Substituted lactams as inhibitors of Aβ protein production
US6960576B2 (en) 1999-09-13 2005-11-01 Bristol-Myers Squibb Pharma Company Hydroxyalkanoylaminolactams and related structures as inhibitors of Aβ protein production
US6962913B2 (en) 1998-08-07 2005-11-08 Bristol-Myers Squibb Company Benzo-1,4-diazepin-2-ones as inhibitors of Aβ protein production
US7053084B1 (en) 1998-12-24 2006-05-30 Bristol-Myers Squibb Company Succinoylamino benzodiazepines as inhibitors of Aβ protein production
US7304056B2 (en) 1998-08-07 2007-12-04 Bristol-Myers Squibb Pharma Company Succinoylamino lactams as inhibitors of Aβ protein production
EP2982668A2 (fr) 2002-12-03 2016-02-10 Pharmacyclics LLC Dérivés de 2-(2-hydroxybiphényl-3-yl)-1h-benzoimidazole-5-carboxamidine en tant qu'inhibiteurs du facteur viia inhibitors pour le traitement de maladies thromboemboliques
US9815850B2 (en) 2016-02-05 2017-11-14 Denali Therapeutics Inc. Compounds, compositions and methods
US11072618B2 (en) 2016-12-09 2021-07-27 Denali Therapeutics Inc. Compounds, compositions and methods
US11999750B2 (en) 2022-01-12 2024-06-04 Denali Therapeutics Inc. Crystalline forms of (S)-5-benzyl-N-(5-methyl-4-oxo-2,3,4,5-tetrahydropyrido [3,2-B][1,4]oxazepin-3-yl)-4H-1,2,4-triazole-3-carboxamide

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100471856C (zh) * 2003-07-31 2009-03-25 Irm责任有限公司 作为pdf抑制剂的二环化合物和组合物

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995035311A1 (fr) * 1994-06-17 1995-12-28 Corvas International, Inc. Derives de l'acide 3-amino-2-oxo-1-piperidineacetique
WO1996019491A1 (fr) * 1994-12-22 1996-06-27 Biochem Pharma Inc. Peptides de cetoarginine heterocycliques utilises comme inhibiteurs de thrombine
WO1998016523A2 (fr) * 1996-10-11 1998-04-23 Cor Therapeutics, Inc. Inhibiteurs competitifs du facteur xa

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995035311A1 (fr) * 1994-06-17 1995-12-28 Corvas International, Inc. Derives de l'acide 3-amino-2-oxo-1-piperidineacetique
WO1996019491A1 (fr) * 1994-12-22 1996-06-27 Biochem Pharma Inc. Peptides de cetoarginine heterocycliques utilises comme inhibiteurs de thrombine
WO1998016523A2 (fr) * 1996-10-11 1998-04-23 Cor Therapeutics, Inc. Inhibiteurs competitifs du facteur xa

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
J. E. SEMPLE: "Design, synthesis, and evolution of a novel, selective, and orally bioavailable class of thrombin inhibitors: P1-argininal derivatives incorporating P3-4 lactam sulfonamide moieties", JOURNAL OF MEDICINAL CHEMISTRY, vol. 39, no. 23, 1996, pages 4531 - 36, XP002081550 *
KUNITADA S ET AL: "FACTOR XA INHIBITORS", CURRENT PHARMACEUTICAL DESIGN, vol. 2, no. 5, October 1996 (1996-10-01), pages 531 - 542, XP002057653 *

Cited By (56)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6194435B1 (en) 1996-10-11 2001-02-27 Cor Therapeutics, Inc. Lactams as selective factor Xa inhibitors
US6262047B1 (en) 1996-10-11 2001-07-17 Cor Therapeutics, Inc. Selective factor Xa inhibitors
US6525076B1 (en) 1996-10-11 2003-02-25 Millennium Pharmaceuticals, Inc. Selective factor Xa inhibitors
US6369080B2 (en) 1996-10-11 2002-04-09 Cor Therapeutics, Inc. Selective factor Xa inhibitors
US6369063B1 (en) 1997-04-14 2002-04-09 Cor Therapeutics, Inc. Selective factor Xa inhibitors
US6204268B1 (en) 1997-04-14 2001-03-20 Cor Therapeutics, Inc Selective factor Xa inhibitors
US6211183B1 (en) 1997-04-14 2001-04-03 Cor Therapeutics, Inc. Selective factor Xa inhibitors
US6133256A (en) * 1997-04-14 2000-10-17 Cor Therapeutics Inc Selective factor Xa inhibitors
US6218382B1 (en) 1997-08-11 2001-04-17 Cor Therapeutics, Inc Selective factor Xa inhibitors
US6228854B1 (en) 1997-08-11 2001-05-08 Cor Therapeutics, Inc. Selective factor Xa inhibitors
US6333321B1 (en) 1997-08-11 2001-12-25 Cor Therapeutics, Inc. Selective factor Xa inhibitors
US7304056B2 (en) 1998-08-07 2007-12-04 Bristol-Myers Squibb Pharma Company Succinoylamino lactams as inhibitors of Aβ protein production
US7304055B2 (en) 1998-08-07 2007-12-04 Bristol-Myers Squibb Pharma Company Succinoylamino lactams as inhibitors of Aβ protein production
US7507815B2 (en) 1998-08-07 2009-03-24 Bristol-Myers Squibb Pharma Company Succinoylamino lactams as inhibitors of a-β protein production
US6962913B2 (en) 1998-08-07 2005-11-08 Bristol-Myers Squibb Company Benzo-1,4-diazepin-2-ones as inhibitors of Aβ protein production
US7101870B2 (en) 1998-08-07 2006-09-05 Bristol-Myers Squibb Pharma Company Succinoylamino lactams as inhibitors of A-β protein production
US7456172B2 (en) 1998-12-24 2008-11-25 Bristol-Myers Squibb Pharma Company Succinoylamino benzodiazepines as inhibitors of Aβ protein production
US7304049B2 (en) 1998-12-24 2007-12-04 Bristol-Myers Squibb Pharma Company Succinoylaminobenzodiazepines as inhibitors of Aβ protein production
US7718795B2 (en) 1998-12-24 2010-05-18 Bristol-Myers Squibb Pharma Company Succinoylamino benzodiazepines as inhibitors of aβ protein production
US7053084B1 (en) 1998-12-24 2006-05-30 Bristol-Myers Squibb Company Succinoylamino benzodiazepines as inhibitors of Aβ protein production
US6297233B1 (en) 1999-02-09 2001-10-02 Bristol-Myers Squibb Company Lactam inhibitors of FXa and method
US7423033B2 (en) 1999-09-13 2008-09-09 Bristol-Myers Squibb Pharma Company Hydroxyalkanoylaminolactams and related structures as inhibitors of aβ protein production
US7342008B2 (en) 1999-09-13 2008-03-11 Bristol-Myers Squibb Pharma Company Hydroxyalkanoylaminolactams and related structures as inhibitors of Aβ protein production
US6469029B1 (en) 1999-09-13 2002-10-22 3-Dimensional Pharmaceuticals, Inc. Azacycloalkanone serine protease inhibitors
US6503902B2 (en) 1999-09-13 2003-01-07 Bristol-Myers Squibb Pharma Company Hydroxyalkanoylaminolactams and related structures as inhibitors of a β protein production
US7112583B2 (en) 1999-09-13 2006-09-26 Bristol-Myers Squibb Pharma Company Hydroxyalkanoylaminolactams and related structures as inhibitors of Aβ protein production
US6960576B2 (en) 1999-09-13 2005-11-01 Bristol-Myers Squibb Pharma Company Hydroxyalkanoylaminolactams and related structures as inhibitors of Aβ protein production
US6962942B2 (en) 1999-09-13 2005-11-08 3-Dimensional Pharmaceuticals, Inc. Azacycloalkanone serine protease inhibitors
US6503901B1 (en) 1999-10-08 2003-01-07 Bristol Myers Squibb Pharma Company Amino lactam sulfonamides as inhibitors of Aβ protein production
US6525044B2 (en) 2000-02-17 2003-02-25 Bristol-Myers Squibb Company Succinoylamino carbocycles and heterocycles as inhibitors of a-β protein production
US6495540B2 (en) 2000-03-28 2002-12-17 Bristol - Myers Squibb Pharma Company Lactams as inhibitors of A-β protein production
US6713476B2 (en) 2000-04-03 2004-03-30 Dupont Pharmaceuticals Company Substituted cycloalkyls as inhibitors of a beta protein production
US7276496B2 (en) 2000-04-03 2007-10-02 Bristol-Myers Squibb Pharma Company Cyclic malonamides as inhibitors of Aβ protein protection
US6759404B2 (en) 2000-04-03 2004-07-06 Richard E. Olson Cyclic malonamides as inhibitors of aβ protein production
US7390896B2 (en) 2000-04-03 2008-06-24 Bristol-Myers Squibb Pharma Corporation Cyclic malonamides as inhibitors of Aβ protein production
US7528249B2 (en) 2000-04-03 2009-05-05 Bristol-Myers Squibb Pharma Company Cyclic malonamides as inhibitors of aβ protein production
US7053081B2 (en) 2000-04-03 2006-05-30 Bristol-Myers Squibb Pharma Company Cyclic malonamides as inhibitors of A-β protein production
US6900199B2 (en) 2000-04-11 2005-05-31 Bristol-Myers Squibb Pharma Company Substituted lactams as inhibitors of Aβ protein production
US7498324B2 (en) 2000-04-11 2009-03-03 Bristol-Myers Squibb Pharma Company Substituted lactams as inhibitors of Aβ protein production
US7276495B2 (en) 2000-04-11 2007-10-02 Bristol-Myers Squibb Pharma Company Substituted lactams as inhibitors of Aβ protein production
US7655647B2 (en) 2000-04-11 2010-02-02 Bristol-Myers Squibb Pharma Company Substituted lactams as inhibitors of Aβ protein production
US7390802B2 (en) 2000-04-11 2008-06-24 Bristol-Myers Squibb Pharma Corporation Substituted lactams as inhibitors of Aβ protein production
WO2001079261A1 (fr) * 2000-04-14 2001-10-25 Corvas International, Inc. Derives de tetrahydro-azepinone servant d'inhibiteurs de la thrombine
US6509333B2 (en) 2000-06-01 2003-01-21 Bristol-Myers Squibb Pharma Company Lactams substituted by cyclic succinates as inhibitors of Aβ protein production
US7456278B2 (en) 2000-06-01 2008-11-25 Bristol-Myers Squibb Pharma Corporation Lactams substituted by cyclic succinates as inhibitors of Aβ protein production
US7354914B2 (en) 2000-06-01 2008-04-08 Bristol-Myers Squibb Pharma Company Lactams substituted by cyclic succinates as inhibitors of Aβ protein production
US6958329B2 (en) 2000-06-01 2005-10-25 Bristol-Myers Squibb Pharma Company Lactams substituted by cyclic succinates as inhibitors of A-β protein production
US6511973B2 (en) 2000-08-02 2003-01-28 Bristol-Myers Squibb Co. Lactam inhibitors of FXa and method
EP2982668A2 (fr) 2002-12-03 2016-02-10 Pharmacyclics LLC Dérivés de 2-(2-hydroxybiphényl-3-yl)-1h-benzoimidazole-5-carboxamidine en tant qu'inhibiteurs du facteur viia inhibitors pour le traitement de maladies thromboemboliques
US9815850B2 (en) 2016-02-05 2017-11-14 Denali Therapeutics Inc. Compounds, compositions and methods
US9896458B2 (en) 2016-02-05 2018-02-20 Denali Therapeutics Inc. Compounds, compositions and methods
US10131676B2 (en) 2016-02-05 2018-11-20 Denali Therapeutics Inc. Compounds, compositions and methods
US10604535B2 (en) 2016-02-05 2020-03-31 Denali Therapeutics Inc. Compounds, compositions and methods
US11072618B2 (en) 2016-12-09 2021-07-27 Denali Therapeutics Inc. Compounds, compositions and methods
US12180211B2 (en) 2016-12-09 2024-12-31 Denali Therapeutics Inc. Compounds, compositions and methods
US11999750B2 (en) 2022-01-12 2024-06-04 Denali Therapeutics Inc. Crystalline forms of (S)-5-benzyl-N-(5-methyl-4-oxo-2,3,4,5-tetrahydropyrido [3,2-B][1,4]oxazepin-3-yl)-4H-1,2,4-triazole-3-carboxamide

Also Published As

Publication number Publication date
JP2001515842A (ja) 2001-09-25
EP0994894A1 (fr) 2000-04-26
CA2299610A1 (fr) 1999-02-18
NZ502876A (en) 2001-11-30

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