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WO2001079195A3 - Pyridine and pyrazine derivatives as thrombin inhibitors - Google Patents

Pyridine and pyrazine derivatives as thrombin inhibitors Download PDF

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Publication number
WO2001079195A3
WO2001079195A3 PCT/US2001/012276 US0112276W WO0179195A3 WO 2001079195 A3 WO2001079195 A3 WO 2001079195A3 US 0112276 W US0112276 W US 0112276W WO 0179195 A3 WO0179195 A3 WO 0179195A3
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WO
WIPO (PCT)
Prior art keywords
compounds
pyridine
thrombin inhibitors
pyrazine derivatives
pharmaceutical compositions
Prior art date
Application number
PCT/US2001/012276
Other languages
French (fr)
Other versions
WO2001079195A9 (en
WO2001079195A2 (en
Inventor
Joseph Edward Semple
Jingjong Jean Cui
Jonathan Zhangi Ho
Odile Esther Levy
Gian Luca Araldi
Original Assignee
Corvas Int Inc
Joseph Edward Semple
Jingjong Jean Cui
Jonathan Zhangi Ho
Odile Esther Levy
Gian Luca Araldi
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 Corvas Int Inc, Joseph Edward Semple, Jingjong Jean Cui, Jonathan Zhangi Ho, Odile Esther Levy, Gian Luca Araldi filed Critical Corvas Int Inc
Priority to AU2001255399A priority Critical patent/AU2001255399A1/en
Publication of WO2001079195A2 publication Critical patent/WO2001079195A2/en
Publication of WO2001079195A3 publication Critical patent/WO2001079195A3/en
Publication of WO2001079195A9 publication Critical patent/WO2001079195A9/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/72—Nitrogen atoms
    • C07D213/76—Nitrogen atoms to which a second hetero atom is attached
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10—Heterocyclic 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
    • C07D241/14—Heterocyclic 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
    • C07D241/20—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic 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
    • C07D401/02—Heterocyclic 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
    • C07D401/12—Heterocyclic 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
    • 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
    • C07D403/12—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 linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing three or more hetero rings
    • 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
    • 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
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • C07D417/02—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 two hetero rings
    • C07D417/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • 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
    • 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
    • C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

The present invention provides compounds which have a pyrazinone or pyridinone ring at P3 and which feature at P1 a cyclic amino or amidino derivative. These compounds have biological activity as active and potent inhibitors of thrombin. Their pharmaceutically acceptable salts, pharmaceutical compositions thereof and methods of using these compounds and pharmaceutical compositions comprising these compounds as therapeutic agents for treatment of disease states in mammals which are characterized by abnormal thrombosis are also described.
PCT/US2001/012276 2000-04-14 2001-04-13 Pyridine and pyrazine derivatives as thrombin inhibitors WO2001079195A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2001255399A AU2001255399A1 (en) 2000-04-14 2001-04-13 Pyridine and pyrazine derivatives as thrombin inhibitors

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US54945200A 2000-04-14 2000-04-14
US55009300A 2000-04-14 2000-04-14
US09/549,452 2000-04-14
US09/550,093 2000-04-14

Publications (3)

Publication Number Publication Date
WO2001079195A2 WO2001079195A2 (en) 2001-10-25
WO2001079195A3 true WO2001079195A3 (en) 2002-05-16
WO2001079195A9 WO2001079195A9 (en) 2003-10-23

Family

ID=27069137

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2001/012276 WO2001079195A2 (en) 2000-04-14 2001-04-13 Pyridine and pyrazine derivatives as thrombin inhibitors

Country Status (2)

Country Link
AU (1) AU2001255399A1 (en)
WO (1) WO2001079195A2 (en)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MXPA04003167A (en) * 2001-10-03 2004-07-08 Pharmacia Corp 6-membered unsaturated heterocyclic compounds useful for selective inhibition of the coagulation cascade.
SI21097A (en) * 2001-12-04 2003-06-30 Univerza V Ljubljani Thrombine inhibitors
US11584714B2 (en) 2018-05-29 2023-02-21 Omeros Corporation MASP-2 inhibitors and methods of use
AU2020395306A1 (en) 2019-12-04 2022-06-30 Omeros Corporation MASP-2 inhibitors and methods of use
EP4069238A1 (en) 2019-12-04 2022-10-12 Omeros Corporation Masp-2 inhibitors and methods of use

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997001338A1 (en) * 1995-06-27 1997-01-16 Merck & Co., Inc. Pyridinone-thrombin inhibitors
WO1997030708A1 (en) * 1996-02-22 1997-08-28 Merck & Co., Inc. Pyridinone thrombin inhibitors
WO1997046207A2 (en) * 1996-06-07 1997-12-11 Corvas International, Inc. Aromatic heterocyclic derivatives as enzyme inhibitors
WO1999011267A1 (en) * 1997-09-05 1999-03-11 Merck & Co., Inc. Pyrazinone thrombin inhibitors
WO1999061442A1 (en) * 1998-05-26 1999-12-02 Merck & Co., Inc. Imidazopyridine thrombin inhibitors
WO2000032574A1 (en) * 1998-11-27 2000-06-08 Sanofi-Synthelabo Novel 2-pyridone derivatives, preparation method and therapeutic use
WO2000069834A1 (en) * 1999-05-19 2000-11-23 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl pyrazinones useful for selective inhibition of the coagulation cascade
WO2000069826A1 (en) * 1999-05-19 2000-11-23 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl pyridones useful for selective inhibition of the coagulation cascade

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997001338A1 (en) * 1995-06-27 1997-01-16 Merck & Co., Inc. Pyridinone-thrombin inhibitors
WO1997030708A1 (en) * 1996-02-22 1997-08-28 Merck & Co., Inc. Pyridinone thrombin inhibitors
WO1997046207A2 (en) * 1996-06-07 1997-12-11 Corvas International, Inc. Aromatic heterocyclic derivatives as enzyme inhibitors
WO1999011267A1 (en) * 1997-09-05 1999-03-11 Merck & Co., Inc. Pyrazinone thrombin inhibitors
WO1999061442A1 (en) * 1998-05-26 1999-12-02 Merck & Co., Inc. Imidazopyridine thrombin inhibitors
WO2000032574A1 (en) * 1998-11-27 2000-06-08 Sanofi-Synthelabo Novel 2-pyridone derivatives, preparation method and therapeutic use
WO2000069834A1 (en) * 1999-05-19 2000-11-23 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl pyrazinones useful for selective inhibition of the coagulation cascade
WO2000069826A1 (en) * 1999-05-19 2000-11-23 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl pyridones useful for selective inhibition of the coagulation cascade

Also Published As

Publication number Publication date
WO2001079195A9 (en) 2003-10-23
WO2001079195A2 (en) 2001-10-25
AU2001255399A1 (en) 2001-10-30

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