WO2003047564A1 - Derivative having hiv integrase inhibitory activity - Google Patents

Derivative having hiv integrase inhibitory activity Download PDF

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Publication number
WO2003047564A1
WO2003047564A1 PCT/JP2002/012582 JP0212582W WO03047564A1 WO 2003047564 A1 WO2003047564 A1 WO 2003047564A1 JP 0212582 W JP0212582 W JP 0212582W WO 03047564 A1 WO03047564 A1 WO 03047564A1
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WO
WIPO (PCT)
Prior art keywords
inhibitory activity
derivative
ring
integrase inhibitory
hiv integrase
Prior art date
Application number
PCT/JP2002/012582
Other languages
French (fr)
Japanese (ja)
Inventor
Hitoshi Murai
Noriyuki Kurose
Original Assignee
Shionogi & Co., Ltd.
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 Shionogi & Co., Ltd. filed Critical Shionogi & Co., Ltd.
Priority to AU2002349675A priority Critical patent/AU2002349675A1/en
Priority to JP2003548820A priority patent/JP4497347B2/en
Publication of WO2003047564A1 publication Critical patent/WO2003047564A1/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
    • C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
    • C07D213/46—Oxygen atoms
    • C07D213/50—Ketonic radicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4196—1,2,4-Triazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/443—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/538—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with carbocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Virology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • AIDS & HIV (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Molecular Biology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Abstract

A compound represented by the formula (I): [wherein RC and RD in combination form a ring in cooperation with the adjacent carbon atoms, provided that the ring may be a fused ring; Y is =O, =S, =N-RE, etc.; Z is =O, =S, or =NH; and RA is a group represented by the formula (II) (wherein ring C is a nitrogenous aromatic heterocycle), etc.]. It was found to have integrase inhibitory activity.
PCT/JP2002/012582 2001-12-05 2002-12-02 Derivative having hiv integrase inhibitory activity WO2003047564A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU2002349675A AU2002349675A1 (en) 2001-12-05 2002-12-02 Derivative having hiv integrase inhibitory activity
JP2003548820A JP4497347B2 (en) 2001-12-05 2002-12-02 Derivatives having HIV integrase inhibitory activity

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2001-371436 2001-12-05
JP2001371436 2001-12-05

Publications (1)

Publication Number Publication Date
WO2003047564A1 true WO2003047564A1 (en) 2003-06-12

Family

ID=19180478

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2002/012582 WO2003047564A1 (en) 2001-12-05 2002-12-02 Derivative having hiv integrase inhibitory activity

Country Status (3)

Country Link
JP (1) JP4497347B2 (en)
AU (1) AU2002349675A1 (en)
WO (1) WO2003047564A1 (en)

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6953858B2 (en) 2001-06-11 2005-10-11 Agouron Pharmaceuticals, Inc. HIV protease inhibitors, compositions containing the same, their pharmaceutical uses and materials for their synthesis
US7001912B2 (en) 2003-01-27 2006-02-21 Agouron Pharmaceuticals, Inc. HIV-integrase inhibitors, pharmaceutical compositions, and methods for their use
US7094909B2 (en) 2001-06-11 2006-08-22 Agouron Pharmaceuticals, Inc. HIV protease inhibitors, compositions containing the same, their pharmaceutical uses and materials for their synthesis
JP2006342115A (en) * 2005-06-10 2006-12-21 Shionogi & Co Ltd Polycyclic compound having hiv integrase inhibition activity
US7169932B2 (en) 2001-06-11 2007-01-30 Pfizer Inc. HIV protease inhibitors, compositions containing the same, their pharmaceutical uses, material for their synthesis
US7211572B2 (en) 2003-08-13 2007-05-01 Japan Tobacco Inc. Nitrogen-containing fused ring compound and use thereof as HIV integrase inhibitor
US7217713B2 (en) 2001-10-26 2007-05-15 Istituto Di Richerche Di Biologia Molecolare P. Angeletti S.P.A. N-substituted hydroxypyrimidinone carboxamide inhibitors of HIV integrase
WO2008004100A2 (en) 2006-07-05 2008-01-10 Pfizer Products Inc. Therapeutic compounds
US7368571B2 (en) 2002-10-31 2008-05-06 Pfizer Inc HIV-Integrase inhibitors, pharmaceutical compositions and methods for their use
US7468375B2 (en) 2004-04-26 2008-12-23 Pfizer Inc. Inhibitors of the HIV integrase enzyme
US7692014B2 (en) 2004-04-26 2010-04-06 Pfizer, Inc. Inhibitors of the HIV integrase enzyme
WO2011076765A1 (en) 2009-12-23 2011-06-30 Katholieke Universiteit Leuven Novel antiviral compounds
WO2012065963A2 (en) 2010-11-15 2012-05-24 Katholieke Universiteit Leuven Novel antiviral compounds
WO2012066442A1 (en) 2010-11-15 2012-05-24 Pfizer Limited Inhibitors of hiv replication
WO2013091089A1 (en) * 2011-12-22 2013-06-27 UNIVERSITé LAVAL Three-dimensional cavities of dendritic cell immunoreceptor (dcir), compounds binding thereto and therapeutic applications related to inhibition of human immunodeficiency virus type-1 (hiv-1)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000039086A1 (en) * 1998-12-25 2000-07-06 Shionogi & Co., Ltd. Aromatic heterocycle compounds having hiv integrase inhibiting activities
WO2001017968A1 (en) * 1999-09-02 2001-03-15 Shionogi & Co., Ltd. Integrase inhibitors containing aromatic heterocycle derivatives
WO2001095905A1 (en) * 2000-06-14 2001-12-20 Shionogi & Co., Ltd. Inhibitor for enzyme having two divalent metal ions as active centers
WO2002036734A2 (en) * 2000-10-12 2002-05-10 Merck & Co., Inc. Aza-and polyaza-naphthalenyl ketones useful as hiv integrase inhibitors
WO2002070491A1 (en) * 2001-03-01 2002-09-12 Shionogi & Co., Ltd. Nitrogenous heteroaromatic ring derivative having hiv integrase inhibitory activity

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4569942A (en) * 1984-05-04 1986-02-11 Pfizer Inc. N,3-Disubstituted 2-oxindole-1-carboxamides as analgesic and antiinflammatory agents
US5457237A (en) * 1991-05-29 1995-10-10 Pfizer Inc. Dihydroxyindanone tyrosine kinase inhibitors

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000039086A1 (en) * 1998-12-25 2000-07-06 Shionogi & Co., Ltd. Aromatic heterocycle compounds having hiv integrase inhibiting activities
WO2001017968A1 (en) * 1999-09-02 2001-03-15 Shionogi & Co., Ltd. Integrase inhibitors containing aromatic heterocycle derivatives
WO2001095905A1 (en) * 2000-06-14 2001-12-20 Shionogi & Co., Ltd. Inhibitor for enzyme having two divalent metal ions as active centers
WO2002036734A2 (en) * 2000-10-12 2002-05-10 Merck & Co., Inc. Aza-and polyaza-naphthalenyl ketones useful as hiv integrase inhibitors
WO2002070491A1 (en) * 2001-03-01 2002-09-12 Shionogi & Co., Ltd. Nitrogenous heteroaromatic ring derivative having hiv integrase inhibitory activity

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7179918B2 (en) 2001-06-11 2007-02-20 Agouron Pharmaceuticals, Inc. HIV protease inhibitors, compositions containing the same, their pharmaceutical uses and materials for their synthesis
US7094909B2 (en) 2001-06-11 2006-08-22 Agouron Pharmaceuticals, Inc. HIV protease inhibitors, compositions containing the same, their pharmaceutical uses and materials for their synthesis
US6953858B2 (en) 2001-06-11 2005-10-11 Agouron Pharmaceuticals, Inc. HIV protease inhibitors, compositions containing the same, their pharmaceutical uses and materials for their synthesis
US7169932B2 (en) 2001-06-11 2007-01-30 Pfizer Inc. HIV protease inhibitors, compositions containing the same, their pharmaceutical uses, material for their synthesis
US7435734B2 (en) 2001-10-26 2008-10-14 Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. N-substituted hydroxypyrimidinone carboxamide inhibitors of HIV integrase
US7217713B2 (en) 2001-10-26 2007-05-15 Istituto Di Richerche Di Biologia Molecolare P. Angeletti S.P.A. N-substituted hydroxypyrimidinone carboxamide inhibitors of HIV integrase
US7368571B2 (en) 2002-10-31 2008-05-06 Pfizer Inc HIV-Integrase inhibitors, pharmaceutical compositions and methods for their use
US7138408B2 (en) 2003-01-27 2006-11-21 Agouron Pharmaceuticals, Inc. HIV integrase inhibitors, pharmaceutical compositions and methods for their use
US7001912B2 (en) 2003-01-27 2006-02-21 Agouron Pharmaceuticals, Inc. HIV-integrase inhibitors, pharmaceutical compositions, and methods for their use
EP2042502A1 (en) 2003-08-13 2009-04-01 Japan Tobacco Inc. Nitrogen-containing fused ring compound and use thereof as HIV integrase inhibitor
US7211572B2 (en) 2003-08-13 2007-05-01 Japan Tobacco Inc. Nitrogen-containing fused ring compound and use thereof as HIV integrase inhibitor
US7468375B2 (en) 2004-04-26 2008-12-23 Pfizer Inc. Inhibitors of the HIV integrase enzyme
US7692014B2 (en) 2004-04-26 2010-04-06 Pfizer, Inc. Inhibitors of the HIV integrase enzyme
JP2006342115A (en) * 2005-06-10 2006-12-21 Shionogi & Co Ltd Polycyclic compound having hiv integrase inhibition activity
WO2008004100A2 (en) 2006-07-05 2008-01-10 Pfizer Products Inc. Therapeutic compounds
WO2011076765A1 (en) 2009-12-23 2011-06-30 Katholieke Universiteit Leuven Novel antiviral compounds
WO2012065963A2 (en) 2010-11-15 2012-05-24 Katholieke Universiteit Leuven Novel antiviral compounds
WO2012066442A1 (en) 2010-11-15 2012-05-24 Pfizer Limited Inhibitors of hiv replication
WO2013091089A1 (en) * 2011-12-22 2013-06-27 UNIVERSITé LAVAL Three-dimensional cavities of dendritic cell immunoreceptor (dcir), compounds binding thereto and therapeutic applications related to inhibition of human immunodeficiency virus type-1 (hiv-1)
US9731001B2 (en) 2011-12-22 2017-08-15 Universite Laval Three-dimensional cavities of dendritic cell immunoreceptor (DCIR), compounds binding thereto and therapeutic applications related to inhibition of human immunodeficiency virus type-1 (HIV-1)

Also Published As

Publication number Publication date
JP4497347B2 (en) 2010-07-07
JPWO2003047564A1 (en) 2005-04-14
AU2002349675A1 (en) 2003-06-17

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