CA2796744A1 - Synthetic metabolites of fluoro substituted omega-carboxyaryl diphenyl urea for the treatment and prevention of diseases and conditions - Google Patents

Synthetic metabolites of fluoro substituted omega-carboxyaryl diphenyl urea for the treatment and prevention of diseases and conditions Download PDF

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Publication number
CA2796744A1
CA2796744A1 CA2796744A CA2796744A CA2796744A1 CA 2796744 A1 CA2796744 A1 CA 2796744A1 CA 2796744 A CA2796744 A CA 2796744A CA 2796744 A CA2796744 A CA 2796744A CA 2796744 A1 CA2796744 A1 CA 2796744A1
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CA
Canada
Prior art keywords
synthetic
formula
metabolites
diseases
prevention
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.)
Abandoned
Application number
CA2796744A
Other languages
French (fr)
Inventor
Scott Wilhelm
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.)
Bayer Healthcare LLC
Original Assignee
Bayer Healthcare LLC
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 Bayer Healthcare LLC filed Critical Bayer Healthcare LLC
Publication of CA2796744A1 publication Critical patent/CA2796744A1/en
Abandoned legal-status Critical Current

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Classifications

    • 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
    • A61K31/4412—Non condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • 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
    • C07D213/89—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 with hetero atoms directly attached to the ring nitrogen atom
    • 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

Abstract

Synthetic metabolites of compounds of Formula (I); salts thereof, prodrugs thereof, pharmaceutical compositions containing such synthetic metabolites, and use of such compound and compositions to treat diseases mediated by raf, VEGFR, PDGFR, p38 and flt-3. Described are M2, M3, M4, and M5 synthetic metabolites of compounds of formula I, wherein the structures of said compound of formula I and said M2, M3, M4, and M5 synthetic metabolites are:

Claims (4)

  1. Claim 1. An M2, M3, M4, or M5 synthetic metabolite of a compound of Formula I
    or a salt or a prodrug or a stereoisomer of said synthetic metabolite, wherein the structures of said compound of formula I and said M2, M3, M4, and M5 synthetic metabolites are:

  2. Claim 2. The synthetic metabolite according to claim 1 or a salt or a prodrug or a stereoisomer of said synthetic metabolite, which is an M2 or an M5 synthetic metabolite having the following strucutural formula:

  3. Claim 3. A method of inhibiting tumor growth in a subject comprising administering to said subject the synthetic metabolite according to claim 1 or a pharmaceutical composition comprising said synthetic metabolite.
  4. Claim 4. A method of making the synthetic metabolite according to claim 1, comprising contacting a compound of formula I or a salt thereof with a liver microsome preparation under conditions sufficient for the metabolism of said compound of Formula I
    and isolating the metabolites from said preparation.
CA2796744A 2010-04-17 2011-04-18 Synthetic metabolites of fluoro substituted omega-carboxyaryl diphenyl urea for the treatment and prevention of diseases and conditions Abandoned CA2796744A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US32529410P 2010-04-17 2010-04-17
US61/325,294 2010-04-17
PCT/US2011/032835 WO2011130728A1 (en) 2010-04-17 2011-04-18 Synthetic metabolites of fluoro substituted omega-carboxyaryl diphenyl urea for the treatment and prevention diseases and conditions

Publications (1)

Publication Number Publication Date
CA2796744A1 true CA2796744A1 (en) 2011-10-20

Family

ID=44144967

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2796744A Abandoned CA2796744A1 (en) 2010-04-17 2011-04-18 Synthetic metabolites of fluoro substituted omega-carboxyaryl diphenyl urea for the treatment and prevention of diseases and conditions

Country Status (3)

Country Link
CN (1) CN103079567A (en)
CA (1) CA2796744A1 (en)
WO (1) WO2011130728A1 (en)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102643229A (en) * 2012-01-17 2012-08-22 湖南有色凯铂生物药业有限公司 N-((4-chloro-3-trifluoromethyl) phenyl)-N'-((2-fluoro-4-(2-formamyl)-4-pyridyloxy) phenyl) urea and application thereof serving as anticancer medicament
CN102885814A (en) * 2012-01-17 2013-01-23 湖南有色凯铂生物药业有限公司 Compound and use of compound as anti-cancer medicine
CN103508944A (en) * 2012-06-25 2014-01-15 湖南有色凯铂生物药业有限公司 Crystal form A of N-((4-chloro-3-trifluoromethyl)phenyl)-N'-((2-fluoro-4-(2-formamyl)-4-pyridyloxy)phenyl)urea and preparation method thereof
CN103058922B (en) * 2012-09-06 2014-07-16 湖南有色凯铂生物药业有限公司 Crystal form of aromatic urea for antitumor drug and preparation method of crystal form
CN104250226B (en) * 2013-06-27 2019-04-26 常州方楠医药技术有限公司 A method of preparing Rui Gefeini intermediate
CN104736521B (en) * 2013-09-12 2016-10-12 杭州普晒医药科技有限公司 Rui Gefeini salt crystal formation and its production and use
CN103923001B (en) * 2014-04-30 2016-02-10 药源药物化学（上海）有限公司 Rui Gefeini salt and crystal formation, preparation method
CN105218439B (en) * 2014-06-06 2018-11-20 连云港润众制药有限公司 A kind of crystal of Rui Gefeini and preparation method thereof
CN105566215B (en) * 2014-10-17 2018-02-16 沈阳药科大学 A kind of Rui Gefeini preparation method
CN104592105B (en) * 2015-02-10 2017-01-18 杭州朱养心药业有限公司 Regorafenib and manufacture method thereof
CN107921173B (en) * 2015-08-03 2021-07-06 富士胶片株式会社 Cell structure, non-human model animal, method for producing non-human model animal, and method for evaluating test substance
CN109796401B (en) * 2019-04-04 2023-10-17 新乡双鹭药业有限公司 Preparation method of regorafenib bulk drug
CN112587485A (en) * 2021-01-08 2021-04-02 湖南南新制药股份有限公司 Medicine solid dispersion and preparation method thereof

Family Cites Families (52)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR901228A (en) 1943-01-16 1945-07-20 Deutsche Edelstahlwerke Ag Ring gap magnet system
US4220302A (en) 1978-07-21 1980-09-02 Hampton Diane M Nursing bottle holder
US4683202A (en) 1985-03-28 1987-07-28 Cetus Corporation Process for amplifying nucleic acid sequences
US6040166A (en) 1985-03-28 2000-03-21 Roche Molecular Systems, Inc. Kits for amplifying and detecting nucleic acid sequences, including a probe
US4683195A (en) 1986-01-30 1987-07-28 Cetus Corporation Process for amplifying, detecting, and/or-cloning nucleic acid sequences
US5023252A (en) 1985-12-04 1991-06-11 Conrex Pharmaceutical Corporation Transdermal and trans-membrane delivery of drugs
IL86724A (en) 1987-06-19 1995-01-24 Siska Diagnostics Inc Method and kits for the amplification and detection of nucleic acid sequences
AU622426B2 (en) 1987-12-11 1992-04-09 Abbott Laboratories Assay using template-dependent nucleic acid probe reorganization
CA1340807C (en) 1988-02-24 1999-11-02 Lawrence T. Malek Nucleic acid amplification process
US6054270A (en) 1988-05-03 2000-04-25 Oxford Gene Technology Limited Analying polynucleotide sequences
US5700637A (en) 1988-05-03 1997-12-23 Isis Innovation Limited Apparatus and method for analyzing polynucleotide sequences and method of generating oligonucleotide arrays
US5011472A (en) 1988-09-06 1991-04-30 Brown University Research Foundation Implantable delivery system for biological factors
US5143854A (en) 1989-06-07 1992-09-01 Affymax Technologies N.V. Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof
US5424186A (en) 1989-06-07 1995-06-13 Affymax Technologies N.V. Very large scale immobilized polymer synthesis
DE3938907C2 (en) 1989-11-24 1999-11-04 Dade Behring Marburg Gmbh Means for storing and suspending cells, in particular erythrocytes
US5192744A (en) 1990-01-12 1993-03-09 Northwestern University Method of inhibiting angiogenesis of tumors
CA2036946C (en) 1990-04-06 2001-10-16 Kenneth V. Deugau Indexing linkers
US5210015A (en) 1990-08-06 1993-05-11 Hoffman-La Roche Inc. Homogeneous assay system using the nuclease activity of a nucleic acid polymerase
WO1992007095A1 (en) 1990-10-15 1992-04-30 Stratagene Arbitrarily primed polymerase chain reaction method for fingerprinting genomes
EP0562025B1 (en) 1990-12-06 2001-02-07 Affymetrix, Inc. (a Delaware Corporation) Compounds and their use in a binary synthesis strategy
DE69231853T2 (en) 1991-11-07 2001-09-13 Nanotronics Inc HYBRIDIZING POLYNUCLEOTIDS CONJUGED WITH CHROMOPHORES AND FLUOROPHORS TO GENERATE A DONOR-TO-DONOR ENERGY TRANSFER SYSTEM
US5348853A (en) 1991-12-16 1994-09-20 Biotronics Corporation Method for reducing non-specific priming in DNA amplification
ATE231920T1 (en) 1992-03-11 2003-02-15 Dana Farber Cancer Inst Inc METHOD TO CLONE MRNA
US5262311A (en) 1992-03-11 1993-11-16 Dana-Farber Cancer Institute, Inc. Methods to clone polyA mRNA
AU5298393A (en) 1992-10-08 1994-05-09 Regents Of The University Of California, The Pcr assays to determine the presence and concentration of a target
US5538848A (en) 1994-11-16 1996-07-23 Applied Biosystems Division, Perkin-Elmer Corp. Method for detecting nucleic acid amplification using self-quenching fluorescence probe
US5871918A (en) 1996-06-20 1999-02-16 The University Of North Carolina At Chapel Hill Electrochemical detection of nucleic acid hybridization
US5837682A (en) 1996-03-08 1998-11-17 The Children's Medical Center Corporation Angiostatin fragments and method of use
CA2159830C (en) 1994-04-29 2001-07-03 Timothy M Woudenberg System for real time detection of nucleic acid amplification products
US5723290A (en) 1994-11-03 1998-03-03 Trustees Of The University Of Pennsylvania Methods for profiling mRNA expression in neurites
US5545531A (en) 1995-06-07 1996-08-13 Affymax Technologies N.V. Methods for making a device for concurrently processing multiple biological chip assays
US5994063A (en) 1995-06-23 1999-11-30 Metzker; Michael L. Substituted 4,4-difluoro-4-bora-3A,4A-diaza-s-indacene compounds for homogenous amplification/detection assays
US5712126A (en) 1995-08-01 1998-01-27 Yale University Analysis of gene expression by display of 3-end restriction fragments of CDNA
DE69630142D1 (en) 1995-11-16 2003-10-30 Baylor College Medicine METHOD FOR IDENTIFYING METASTATIC SEQUENCES
DE69726281T2 (en) 1996-03-25 2004-08-26 Juridical Foundation The Chemo-Sero-Therapeutic Research Institute NEW VASILIZER INHIBITOR CONTAINING THE TISSUE FACTOR INHIBITOR (TFPI)
US6117635A (en) 1996-07-16 2000-09-12 Intergen Company Nucleic acid amplification oligonucleotides with molecular energy transfer labels and methods based thereon
WO1998005293A2 (en) 1996-08-02 1998-02-12 The Children's Medical Center Corporation Method of regulating the female reproductive system through angiogenesis inhibitors
US6316479B1 (en) 1997-05-19 2001-11-13 Sugen, Inc. Isoxazole-4-carboxamide compounds active against protein tryosine kinase related disorders
US7928239B2 (en) 1999-01-13 2011-04-19 Bayer Healthcare Llc Inhibition of RAF kinase using quinolyl, isoquinolyl or pyridyl ureas
WO2000042012A1 (en) 1999-01-13 2000-07-20 Bayer Corporation φ-CARBOXYARYL SUBSTITUTED DIPHENYL UREAS AS RAF KINASE INHIBITORS
EP2298311B1 (en) 1999-01-13 2012-05-09 Bayer HealthCare LLC w-Carboxy aryl substituted diphenyl ureas as p38 kinase inhibitors
JP3789066B2 (en) 1999-12-08 2006-06-21 三菱電機株式会社 Liquid crystal display
US8725620B2 (en) 2000-07-10 2014-05-13 Nobuyoshi Morimoto System and method for negotiating improved terms for products and services being purchased through the internet
CA2430180C (en) 2003-05-21 2010-03-16 Royal Group Technologies Limited Cascade shade
UA84156C2 (en) * 2003-07-23 2008-09-25 Байер Фармасьютикалс Корпорейшн Fluoro substituted omega-carboxyaryl diphenyl urea for the treatment and prevention of diseases and conditions
CA2628849A1 (en) * 2005-11-10 2007-05-18 Bayer Healthcare Ag Diaryl urea for treating pulmonary hypertension
WO2007068380A1 (en) * 2005-12-15 2007-06-21 Bayer Healthcare Ag Diaryl urea for treating virus infections
GB0614498D0 (en) * 2006-07-21 2006-08-30 Univ Belfast Improvements in Hydrogen Trapping
US8680124B2 (en) * 2007-01-19 2014-03-25 Bayer Healthcare Llc Treatment of cancers with acquired resistance to kit inhibitors
JP2010516692A (en) * 2007-01-19 2010-05-20 バイエル・ヘルスケア・エルエルシー Treatment of cancer resistant to chemotherapeutic agents
US8312249B1 (en) 2008-10-10 2012-11-13 Apple Inc. Dynamic trampoline and structured code generation in a signed code environment
US9993647B2 (en) 2014-12-31 2018-06-12 Tsinghua University Variable frequency stimulation therapy method

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WO2011130728A1 (en) 2011-10-20
CN103079567A (en) 2013-05-01

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Effective date: 20170418