EP2176266A2 - Imidazo[1,2b]pyridazines substituees constituant des inhibiteurs de kinases, leur production et leur utilisation comme medicaments - Google Patents

Imidazo[1,2b]pyridazines substituees constituant des inhibiteurs de kinases, leur production et leur utilisation comme medicaments

Info

Publication number
EP2176266A2
EP2176266A2 EP06775928A EP06775928A EP2176266A2 EP 2176266 A2 EP2176266 A2 EP 2176266A2 EP 06775928 A EP06775928 A EP 06775928A EP 06775928 A EP06775928 A EP 06775928A EP 2176266 A2 EP2176266 A2 EP 2176266A2
Authority
EP
European Patent Office
Prior art keywords
imidazo
alkyl
pyridazin
optionally
heterocycloalkyl
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.)
Withdrawn
Application number
EP06775928A
Other languages
German (de)
English (en)
Inventor
Olaf Prien
Benjamin Bader
Ulrich ZÜGEL
Stuart James Ince
Christoph Huwe
Karina Schuck
Knut Eis
Ulrich LÜCKING
Rolf Jautelat
Judith GÜNTHER
Manfred Husemann
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 Intellectual Property GmbH
Original Assignee
Bayer Schering Pharma AG
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 Schering Pharma AG filed Critical Bayer Schering Pharma AG
Publication of EP2176266A2 publication Critical patent/EP2176266A2/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • 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
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • 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
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/04—Antipruritics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • 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
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
    • 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
    • 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
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • 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

Definitions

  • R 1 and R 2 are identical or different and are selected from the group consisting of j) -H and jj) optionally mono- or polysubstituted with -HaI 1 -OH, -CN, C 1 -C 6 -alkyl, C 1 -C 6-
  • Alkyl is in each case a straight-chain or branched alkyl radical, such as, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec. Butyl, tert. Butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, nonyl and decyl.
  • alkyl radical such as, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec. Butyl, tert. Butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, nonyl and decyl.
  • Alkoxy is in each case a straight-chain or branched alkoxy radical, such as, for example, methyloxy, ethyloxy, propyloxy, isopropyloxy, butyloxy,
  • heterocycloalkyl As heterocycloalkyl z. Oxiranyl, Oxethanyl, Dioxolanyl, Dithianyl, Dioxanyl, Aziridinyl, Azetidinyl, Tetrahydrofuranyl, Tetrahydropyranyl, Dihydrooxazolyl, Tetrahydrooxazolyl, Tetrahydrothiazolyl, Tetrahydroisoquinolinyl, Octahydroisoquinolinyl, Tetrahydroquinolinyl, Octahydroquinolinyl,
  • Substituents with multiple substitution may be the same or different.
  • the aryl groups contained in R 1 or R 2 , Heteroaryl, C3-C6-cycloalkyl or C3-C6-heterocycloalkyl groups a maximum of 3 of the above-mentioned Substutuenten.
  • Enantiomers are stereoisomers that behave in the same way as image and mirror image and have no plane of symmetry. All stereoisomers that are not enantiomers are called diastereomers. A special case is E / Z (ice / trans) isomers of double bonds.
  • physiologically acceptable salts of organic and inorganic acids are suitable, such as hydrochloric acid, sulfuric acid, phosphoric acid, citric acid, tartaric acid, fumaric acid, maleic acid, malic acid and the like.
  • Preferred compounds of the general formula I are those compounds in which R 1 and R 2 are identical or different and are selected from the group consisting of j) -H and jj) optionally one or more times with -HaI, - OH, - CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -haloalkoxy, C 1 -C 6 -hydroxyalkyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -heterocycloalkyl, C 2 -C 6 -alkynyl, aryl , Aryloxy, heteroaryl, -S-C 1 -C 6 -alkyl, - (CO) -R 6 , -NR 3 R 4 , -NR 3 (CO) -L, or - NR 3 COOR 7 substituted C 1 -C 6 -al
  • R 1 and R 2 are identical or different and are selected from the group consisting of -H, C 1 -C 4 -alkyl substituted by NR 3 R 4 , optionally additionally mono- or polysubstituted with - Hal, -OH, -CN, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 hydroxyalkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 heterocycloalkyl, C 2 -C 6 alkynyl, aryl, aryloxy, heteroaryl, -S-C 1 -C 6 -alkyl, - (CO) -R 6 , -NR 3 (CO) -L, or - NR 3 COOR 7 substituted, optionally one or more times with -HaI
  • Another object of the present invention is a compound of general formula IIa and their use for the preparation of a compound of formula I, in which
  • R 1 and R 2 in addition to the above definition can together form a C 3 -C 6 heterocycloalkyl ring which contains at least one nitrogen atom in the ring and optionally additionally in the ring one or more nitrogen, oxygen or sulfur atoms and / or one or more - ( CO) - or - (SO 2 ) - groups and / or optionally one or more double bonds, wherein the ring formed by R 1 and R 2 optionally singly or multiply with -CN, -HaI, -OH, C1-
  • C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 6 cycloalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 haloalkoxyalkyl, C 1 -C 6 haloalkoxy, C 1 -C 6 alkoxyalkyl, -NR 3 R 4 , -CONR 6 R 7 , - (CO) -R 6 or -COOR 7 and / or substituted with optionally mono- or polysubstituted with -HaI, C 1 -C 6 -alkoxy, C 1 -C 6 -haloalkoxy or - (CO) -R 6 -substituted aryl or heteroaryl can be, with the
  • R 6 and R r are the same or different and are selected from the group consisting of j) -H and jj) optionally mono- or polysubstituted with -HaI, -OH, -CN, substituted C 1 -C 6 -alkyl, C 1 -C 6 Haloalkyl, C1-C6-alkoxy, C1-C6-haloalkoxy,
  • a and B are the same or different and are selected from the group consisting of i) H, Hal, -OH, -NR 3 R 4 , -CN, or -NO 2 , ii) optionally mono- or polysubstituted with Hal, -OH, C 3 -C6-heterocycloalkyl, -NR 3 R 4 , -SO 2 NR 3 R 4 , -SO 2 R 3 or - (CO) -NR 3 -L substituted C1-C6- Alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -haloalkoxy, C 3 -C 6 -cycloalkyl or C 3 -C 6 -heterocycloalkyl, where the C 3 -C 6 -heterocycloalkyl in the ring optionally contains one or more nitrogen, Oxygen and / or sulfur atoms and / or one or more
  • step B4 the product from step B3 is converted to the compound according to general formula I.
  • the isomer mixtures can be prepared by conventional methods such as crystallization, chromatography or salt formation in the isomers, such as. B. are separated into the enantiomers, diastereomers or E / Z isomers, provided that the isomers are not in equilibrium with each other.
  • Step A 4- [3- (2-Methoxy-pyridin-4-yl) -imidazo [1,2-b] pyridazin-6-ylamino] -piperidine-1-carboxylic acid tert-butyl ester (Example 6.1)
  • Suitable assays for testing the effectiveness of the compounds of the invention on the modulation capacity of the kinase activity are known. Furthermore, assays are known to investigate the effectiveness of the compounds of the invention in the modulation of cell proliferation.
  • the following biological examples therefore merely serve to exemplify the uses according to the invention of the claimed compounds and are therefore in no way to be understood as limiting.
  • ALK1 phosphorylates serine / threonine residues of the biotinylated substrate bovine ⁇ -casein in the presence of [ ⁇ - 33 P] ATP.
  • the detection of the radioactively labeled product takes place by binding to streptavidin-coated flashplates.
  • the biotin residues of the biotinylated casein bind with high affinity the streptavidin.
  • Radioactively labeled biotinylated casein produced by the ALK1 kinase reaction causes a chemiluminescent signal after streptavidin-mediated binding to the scintillator-containing surface of the flashplates. This signal is due to the proximity of the radioactive label to the scintillator in the whale surface of the flashplates.
  • the detection of the radioactively labeled product takes place by binding to streptavidin-coated flashplates.
  • the biotin residues of the biotinylated casein bind with high affinity to the streptavidin.
  • Radioactively labeled biotinylated casein produced by the ALK4 kinase reaction causes a chemiluminescent signal after streptavidin-mediated binding to the scintillator-containing surface of the flashplates. This signal is due to the proximity of the radioactive label to the scintillator in the whale surface of the flashplates.
  • Unphosphorylated substrate does not cause signal because it contains no radiolabeled phosphate groups.
  • Free [ ⁇ - 33 P] ATP which remains unbound in the solution (supernatant) is washed from the wells of the flashplates and therefore does not contribute significantly to a background signal.
  • the measured signals are therefore a measure of ALK1 kinase activity. The measurement is performed in a Perkin-Elmer TopCount instrument or a Perkin-Elmer ViewLux instrument.
  • Substrate working solution 0.83 ⁇ M ATP, 1.67 ⁇ M biotinylated oc-casein, 7.4 nCi [ ⁇ - 33 P] ATP / ⁇ l in assay buffer
  • Flashplates Streptavidin-coated Flashplates, Perkin Elmer (384-WeII #
  • Flashplate saturation solution 100 ⁇ M ATP, 0.2% Triton X-100 in PBS
  • IC 50 values are calculated with a 4-parameter fit using in-house software.
  • Fugene and OptiMEM are incubated at RT for 5 min. This mixture is with the
  • DU-145 culture medium
  • Q is aryl or heteroaryl
  • a and B are the same or different and are selected from the group consisting of i) H, Hal, -OH, -NR 3 R 4 , -CN, or -NO 2 , ii) optionally mono- or polysubstituted with Hal, -OH, C 3 -C6-heterocycloalkyl, -NR 3 R 4 or - (CO) -NR 3 -
  • L is optionally mono- or polysubstituted with C 1 -C 6 -alkyl, C 1 -C 6 -hydroxyalkoxy, C 1 -C 6 -alkoxyalkoxy, C 3 -C 6 -heterocycloalkyl, or -NR 3 R 4 , substituted
  • R 1 and R 2 may additionally or alternatively to the above definition together form a C 3 -C 6 -heterocycloalkyl ring which comprises at least one Contains nitrogen atom in the ring and optionally additionally in the ring one or more nitrogen, oxygen or sulfur atoms and / or one or more - (CO) - or - (SO 2 ) - groups and / or optionally may contain one or more double bonds, wherein the ring formed by R 1 and R 2 optionally singly or multiply with -CN, -HaI, -
  • NR 3 R 4 is substituted phenyl, pyridyl, pyrimidinyl, thiophenyl, furyl, imidazolyl, or pyrazolyl.
  • R 1 and R 2 are the same or different and are selected from the group consisting of -H, with NR 3 R 4 substituted C1-C4 alkyl, optionally additionally one or more times with -HaI, -OH , -CN, C1-C6-
  • R 3 and R 4 are the same or different, optionally mono- or polysubstituted with -HaI, -OH, -CN, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -hydroxyalkyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -heterocycloalkyl, C 2 -C 6 -alkyl Alkynyl, aryl, aryloxy, heteroaryl, -NR 6 R 7 , -CONR 6 R 7 , - (CO) -R 6 or -COOR 7 substituted C 1 -C 6 -alkyl, wherein R 3 and
  • R6 and R7 May contain double bonds, and wherein R6 and R7, the same or different, is -H, -OH, C1-C6-alkoxy, or C1-C3-alkyl.
  • step C2 the product from step C1 is converted to an imidazo [1,2-b] pyridazin-6-yl) - (R 1 ) - (R 2 ) by reaction with a compound NHR 1 R 2 in a Buchwald-Hartwig cross-coupling reaction.
  • -amine implemented,
  • step C3 the product from step C2 is reacted with ⁇ / -bromo-succinimide to give a (3-bromo- imidazo [1,2-b] pyridazin-6-yl) - (R 1 ) - (R 2 ) -amine,
  • Y is replaced by -H or -HaI
  • R 1 and R 2 are identical or different and are selected from the group consisting of j) -H and jj) optionally mono- or polysubstituted with -HaI, -OH, -CN 1 C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, C1-C6-hydroxyalkyl, C3-C6-cycloalkyl, C3-C6 heterocycloalkyl, C2-C6-alkynyl, aryl, aryloxy, heteroaryl, -S-C1-C6-alkyl, - (CO) -R 6 , -NR 3 R 4 , -NR 3 (CO) -L, or -NR 3 COOR 7 substituted C1-C6-alkyl, C1-C6-alkoxy, C2-C6-alkenyl, C2-C6 Alkynyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -
  • R 1 and R 2 may additionally or alternatively to the above definition together form a C 3 -C 6 -heterocycloalkyl ring which comprises at least one
  • R 3 and R 4 may additionally or alternatively to the above definition together form a C 3 -C 6 -heterocycloalkyl ring which comprises at least one
  • Heterocycloalkyl in the ring may optionally contain one or more nitrogen, oxygen and / or sulfur atoms and / or one or more - (CO) - or -SO 2 - groups and / or one or more double bonds, and, wherein the substituents may be the same or different when substituted several times
  • Q is aryl or heteroaryl
  • a and B are the same or different and are selected from the group consisting of i) H, Hal, -OH, -NR 3 R 4 , -CN, or -NO 2 , ü) optionally mono- or polysubstituted with Hal, -OH, C 3 -C6-heterocycloalkyl, -NR 3 R 4 or - (CO) -NR 3 -L substituted C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, C 3 -C 6 -cycloalkyl or C 3 -C 4 -cycloalkyl
  • C6-heterocycloalkyl wherein said C 3 -C 6 heterocycloalkyl ring optionally containing one or more nitrogen, oxygen and / or sulfur atoms and / or one or more - (CO) - or - (SO 2) - groups and / or may contain one or more double bonds and iii) -NR 3 (CO) -L, - NR 3 (CO) -NR 3 -L, - (CO) -R 6, -O- (CH 2) P -R 6 , - (CO) - (NR 3 ) -L, -NR 3 (CS) -
  • L optionally mono- or polysubstituted with C 1 -C 6 -alkyl, C 1 -C 6 -hydroxyalkoxy, C 1 -
  • R 3 and R 4 are identical or different and are selected from the group consisting of j) -H, jj) optionally mono- or polysubstituted with -HaI, -OH, -CN, C 1 -C 6 -alkyl,
  • R 3 and R 4 additionally or alternatively to the above definition together form a C 3 -C 6 -heterocycloalkyl ring which contains at least one nitrogen atom in the ring and optionally additionally in the ring one or more nitrogen, oxygen or sulfur atoms and / or one or more - (CO) - or - (SO 2) - groups and / or optionally one or more double bonds may contain, said by R3 and R4 formed ring is optionally mono- or polysubstituted by -CN, -Hal, - OH, C1-C6 alkyl, C3-C6-cycloalkyl, C1-C6-hydroxyalkyl, C1-C6-alkoxyalkyl or with -NR 6 R 7, -CONR 6 R 7, - (CO) -R 6 or -COOR 7 and / or optionally a - or more times with -HaI, C1-C6-alkoxy or - (CO) -R 6 substitute
  • R 6 and R 7 are identical or different and are selected from the group consisting of j) -H, jj) optionally mono- or polysubstituted with -HaI, -OH, -CN, substituted

Abstract

L'invention concerne de nouveaux inhibiteurs de kinases, des procédés de production de ces inhibiteurs, des produits intermédiaires pour produire ces inhibiteurs et des utilisations de ces inhibiteurs.
EP06775928A 2005-09-02 2006-09-01 Imidazo[1,2b]pyridazines substituees constituant des inhibiteurs de kinases, leur production et leur utilisation comme medicaments Withdrawn EP2176266A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102005042742A DE102005042742A1 (de) 2005-09-02 2005-09-02 Substituierte Imidazo[1,2b]pyridazine als Kinase-Inhibitoren, deren Herstellung und Verwendung als Arzneimittel
PCT/DE2006/001564 WO2007025540A2 (fr) 2005-09-02 2006-09-01 Imidazo[1,2b]pyridazines substituees constituant des inhibiteurs de kinases, leur production et leur utilisation comme medicaments

Publications (1)

Publication Number Publication Date
EP2176266A2 true EP2176266A2 (fr) 2010-04-21

Family

ID=37709434

Family Applications (1)

Application Number Title Priority Date Filing Date
EP06775928A Withdrawn EP2176266A2 (fr) 2005-09-02 2006-09-01 Imidazo[1,2b]pyridazines substituees constituant des inhibiteurs de kinases, leur production et leur utilisation comme medicaments

Country Status (5)

Country Link
EP (1) EP2176266A2 (fr)
JP (1) JP5680824B2 (fr)
CA (1) CA2620534C (fr)
DE (1) DE102005042742A1 (fr)
WO (1) WO2007025540A2 (fr)

Families Citing this family (79)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7884109B2 (en) 2005-04-05 2011-02-08 Wyeth Llc Purine and imidazopyridine derivatives for immunosuppression
US7989459B2 (en) 2006-02-17 2011-08-02 Pharmacopeia, Llc Purinones and 1H-imidazopyridinones as PKC-theta inhibitors
PE20080403A1 (es) 2006-07-14 2008-04-25 Amgen Inc Derivados heterociclicos fusionados y metodos de uso
US8198448B2 (en) 2006-07-14 2012-06-12 Amgen Inc. Fused heterocyclic derivatives and methods of use
US8217177B2 (en) 2006-07-14 2012-07-10 Amgen Inc. Fused heterocyclic derivatives and methods of use
TW200817409A (en) * 2006-08-04 2008-04-16 Takeda Pharmaceutical Fused heterocyclic derivative and use thereof
AU2007292924A1 (en) * 2006-09-07 2008-03-13 Biogen Idec Ma Inc. IRAK modulators for treating an inflammatory condition, cell proliferative disorder, immune disorder
TW200837064A (en) 2006-10-04 2008-09-16 Pharmacopeia Inc 8-substituted 2-(benzimidazolyl)purine derivatives for immunosuppression
US7902187B2 (en) 2006-10-04 2011-03-08 Wyeth Llc 6-substituted 2-(benzimidazolyl)purine and purinone derivatives for immunosuppression
AR063142A1 (es) 2006-10-04 2008-12-30 Pharmacopeia Inc Derivados de 2-(bencimidazolil) purina y purinonas 6-sustituidas utiles como inmunosupresores,y composiciones farmaceuticas que los contienen.
EP2089393A1 (fr) * 2006-10-30 2009-08-19 Novartis AG Composés hétérocycliques en tant qu'agents anti-inflammatoires
MX2009004700A (es) * 2006-11-06 2009-05-15 Supergen Inc Derivados de imidazo[1,2-b]piridazin y pirazolo[1,5-a] pirimidina y su uso como inhibidores de proteina cinasa.
AR067326A1 (es) * 2007-05-11 2009-10-07 Novartis Ag Imidazopiridinas y pirrolo -pirimidinas sustituidas como inhibidores de cinasa de lipido
CA2686485A1 (fr) 2007-05-23 2008-11-27 Pharmacopeia, Llc Purinones et 1h-imidazopyridinones en tant qu'inhibiteurs de pkc-theta
FR2918986B1 (fr) * 2007-07-19 2009-09-04 Sanofi Aventis Sa Derives de 6-cycloamino-3-(pyridazin-4-yl)imidazo[1,2-b]- pyridazine, leur preparation et leur application en therapeutique
US7868001B2 (en) * 2007-11-02 2011-01-11 Hutchison Medipharma Enterprises Limited Cytokine inhibitors
WO2009062059A2 (fr) * 2007-11-08 2009-05-14 Pharmacopeia, Inc. Purinones et 1h-imidazopyridinones isomères comme inhibiteurs de pkc-thêta
EP2217601A1 (fr) * 2007-11-08 2010-08-18 Centro Nacional de Investigaciones Oncológicas (CNIO) Imidazopyridazines utilisées comme qu'inhibiteurs de protéine kinases
EP2300469B1 (fr) * 2008-05-13 2015-06-24 Novartis AG Hétérocycles condensés azotés et leurs compositions comme inhibiteurs de kinase
WO2010033941A1 (fr) 2008-09-22 2010-03-25 Array Biopharma Inc. Composés imidazo[1,2b]pyridazine substitués comme inhibiteurs de kinases trk
UY32192A (es) 2008-10-22 2011-05-31 Array Biopharma Inc COMPUESTOS PIRAZOLO[1,5-a]PIRIMIDINA SUSTITUIDA COMO INHIBIDORES DE TRK CINASA
FR2939134A1 (fr) * 2008-12-01 2010-06-04 Sanofi Aventis Derives de 6-cycloamino-3-(1h-pyrrolo°2,3-b!pyridin-4-yl) imidazo°1,2-b!-pyridazine, leur preparation et leur application en therapeutique
FR2940284B1 (fr) * 2008-12-19 2011-02-18 Sanofi Aventis Derives de 6-cycloamino-2,3-di-pyridinyl-imidazo°1,2-b!- pyridazine,leur preparation et leur application en therapeutique
FR2940285A1 (fr) * 2008-12-19 2010-06-25 Sanofi Aventis Derives de 6-cycloamino-2-thienyl-3-(pyridin-4-yl)imidazo °1,2-b!-pyridazine et 6-cycloamino-2-furanyl-3- (pyridin-4-yl)imidazo°1,2-b!-pyridazine, leur preparation et leur application en therapeutique
DE102008062826A1 (de) * 2008-12-23 2010-07-01 Merck Patent Gmbh Pyridazinonderivate
EP2210891A1 (fr) * 2009-01-26 2010-07-28 Domain Therapeutics Nouveaux ligands du récepteur de l'adénosine et leurs utilisations
CA2755285C (fr) * 2009-03-20 2014-02-11 Yunxin Y. Bo Inhibiteurs de pi3 kinase
WO2010132598A1 (fr) * 2009-05-13 2010-11-18 Amgen Inc. Composés hétéroaryle en tant qu'inhibiteurs des pikk
AR077468A1 (es) 2009-07-09 2011-08-31 Array Biopharma Inc Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa
GB201002911D0 (en) * 2010-02-19 2010-04-07 Medical Res Council Compound
HUE035337T2 (en) 2010-05-20 2018-05-02 Array Biopharma Inc Macrocyclic compounds as TRK kinase inhibitors
GB201104669D0 (en) * 2011-03-18 2011-05-04 Medical Res Council Technology Compound
WO2012156367A1 (fr) 2011-05-17 2012-11-22 Bayer Intellectual Property Gmbh Imidazopyridazines amino-substituées en tant qu'inhibiteurs de kinase mknk1
AU2012264884B2 (en) 2011-05-27 2017-03-09 Bayer Intellectual Property Gmbh Chiral synthesis of N-{3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-6-methoxyphenyl}-1-[2,3-dihydroxy-propyl]cyclopropanesulfonamides
EP2714692B1 (fr) 2011-06-01 2017-03-22 Bayer Intellectual Property GmbH Aminoimidazopyridazines substituées
ES2610366T3 (es) * 2011-06-22 2017-04-27 Bayer Intellectual Property Gmbh Heterociclil-aminoimidazopiridazinas
US9040691B2 (en) * 2011-07-01 2015-05-26 Bayer Intellectual Property Gmbh Hydroxymethylaryl-substituted pyrrolotriazines as ALK1 inhibitors
US9102673B2 (en) 2011-07-12 2015-08-11 Merck Sharp & Dohme Corp. Substituted pyrrolo[3,2-c]pyridines as TrkA kinase inhibitors
WO2013013188A1 (fr) 2011-07-21 2013-01-24 Tolero Pharmaceuticals, Inc. Inhibiteurs de protéine kinase hétérocycliques
UA117092C2 (uk) 2011-09-06 2018-06-25 Байєр Інтеллектуал Проперті Гмбх Амінозаміщені імідазопіридазини
JP6174586B2 (ja) 2011-09-23 2017-08-02 バイエル・インテレクチュアル・プロパティ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツングＢａｙｅｒ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ ＧｍｂＨ 置換イミダゾピリダジン
HUE029728T2 (en) * 2011-09-30 2017-03-28 Ipsen Pharma Sas Macrocyclic LRRK2 kinase inhibitors
US9090630B2 (en) * 2011-09-30 2015-07-28 Oncodesign S.A. Macrocyclic FLT3 kinase inhibitors
US20140249147A1 (en) * 2011-10-20 2014-09-04 GlaxoSmithKline, LLC Substituted Bicyclic Aza-Heterocycles and Analogues as Sirtuin Modulators
WO2013087581A1 (fr) 2011-12-12 2013-06-20 Bayer Intellectual Property Gmbh Imidazopyridazines amino-substituées
WO2013144189A1 (fr) 2012-03-29 2013-10-03 Bayer Intellectual Property Gmbh Imidazopyridazines substituées par amino
CA2869212A1 (fr) 2012-04-04 2013-10-10 Bayer Pharma Aktiengesellschaft Imidazopyridazines amino-substituees
US9181261B2 (en) 2012-05-22 2015-11-10 Merck Sharp & Dohme Corp. TrkA kinase inhibitors, compositions and methods thereof
TWI585088B (zh) 2012-06-04 2017-06-01 第一三共股份有限公司 作爲激酶抑制劑之咪唑并［１，２－ｂ］嗒衍生物
CN104797585B (zh) 2012-11-19 2017-08-15 拜耳医药股份公司 氨基咪唑并哒嗪
DK2925757T3 (en) 2012-11-19 2018-01-15 Novartis Ag Compounds and compositions for the treatment of parasitic diseases
CA2899352A1 (fr) 2013-01-30 2014-08-07 Bayer Pharma Aktiengesellschaft Amidoimidazopyridazines a titre d'inhibiteurs de kinases mknk-1
EP2958920A1 (fr) 2013-02-20 2015-12-30 Bayer Pharma Aktiengesellschaft Imidazo[1,2-b]pyridazines substituées comme inhibiteurs de mknk1
CA2901427A1 (fr) * 2013-03-07 2014-09-12 Califia Bio, Inc. Inhibiteurs de kinases de lignee mixte et procedes therapeutiques
AU2014268700B2 (en) 2013-05-20 2018-07-05 University Of Washington Through Its Center For Commercialization 5-aminopyrazole-4-carboxamide inhibitors of CDPK1 from T. gondii and C. parvum
WO2015039333A1 (fr) 2013-09-22 2015-03-26 Merck Sharp & Dohme Corp. Inhibiteurs de la kinase trka, compositions en contenant et procédés correspondants
WO2015039334A1 (fr) 2013-09-22 2015-03-26 Merck Sharp & Dohme Corp. Inhibiteurs de la kinase trka, compositions en contenant et procédés correspondants
WO2015104254A1 (fr) 2014-01-09 2015-07-16 Bayer Pharma Aktiengesellschaft Imidazopyridazines amido-substituées utiles dans le traitement des troubles hyperprolifératifs et/ou de l'angiogenèse
WO2015143654A1 (fr) 2014-03-26 2015-10-01 Merck Sharp & Dohme Corp. Inhibiteurs de la kinase trka, compositions et méthodes associées
WO2015143652A1 (fr) 2014-03-26 2015-10-01 Merck Sharp & Dohme Corp. Inhibiteurs de la kinase trka, compositions et méthodes associées
WO2015143653A1 (fr) 2014-03-26 2015-10-01 Merck Sharp & Dohme Corp. Inhibiteurs de la kinase trka, compositions et méthodes associées
KR102649887B1 (ko) 2014-11-16 2024-03-22 어레이 바이오파마 인크. (s)-n-(5-((r)-2-(2,5-디플루오로페닐)-피롤리딘-1-일)-피라졸로[1,5-a]피리미딘-3-일)-3-히드록시피롤리딘-1-카르복스아미드 히드로겐 술페이트의 결정질 형태
WO2016161572A1 (fr) 2015-04-08 2016-10-13 Merck Sharp & Dohme Corp. Inhibiteurs de la kinase trka, compositions et procédés associés
TN2018000138A1 (en) 2015-10-26 2019-10-04 Array Biopharma Inc Point mutations in trk inhibitor-resistant cancer and methods relating to the same
US10045991B2 (en) 2016-04-04 2018-08-14 Loxo Oncology, Inc. Methods of treating pediatric cancers
MX2018012163A (es) 2016-04-04 2019-07-08 Loxo Oncology Inc Formulaciones liquidas de (s)-n-(5-((r)-2-(2,5-difluorofenil)-pirr olidin-1-il)-pirazolo[1,5-a]pirimidin-3-il)-3-hidroxipirrolidina- 1-carboxamida.
JP7443057B2 (ja) 2016-05-18 2024-03-05 ロクソ オンコロジー， インコーポレイテッド （Ｓ）－Ｎ－（５－（（Ｒ）－２－（２，５－ジフルオロフェニル）ピロリジン－１－イル）－ピラゾロ［１，５－ａ］ピリミジン－３－イル）－３－ヒドロキシピロリジン－１－カルボキサミドの調製
JOP20190092A1 (ar) 2016-10-26 2019-04-25 Array Biopharma Inc عملية لتحضير مركبات بيرازولو[1، 5-a]بيريميدين وأملاح منها
JOP20190213A1 (ar) 2017-03-16 2019-09-16 Array Biopharma Inc مركبات حلقية ضخمة كمثبطات لكيناز ros1
FI3661935T3 (fi) 2017-08-11 2023-01-13 Kinaasin estäjinä käyttökelpoiset pyratsolipyrimidiinit
JP7278273B2 (ja) * 2017-10-18 2023-05-19 ブループリント メディシンズ コーポレイション アクチビン受容体様キナーゼの阻害剤としての置換ピロロピリジン
CN110734437B (zh) * 2018-07-19 2022-04-08 南京烁慧医药科技有限公司 吡唑并嘧啶化合物和药物组合物及其应用
AU2020221247A1 (en) 2019-02-12 2021-08-05 Sumitomo Pharma Oncology, Inc. Formulations comprising heterocyclic protein kinase inhibitors
CN111718351B (zh) * 2019-03-19 2021-10-12 华中师范大学 含氧取代吡唑并嘧啶化合物和药物组合物及其应用
CN111718349B (zh) * 2019-03-19 2021-11-02 华中师范大学 含氟吡唑并嘧啶化合物和药物组合物及其应用
JP7209415B2 (ja) * 2019-03-19 2023-01-20 セントラル チャイナ ノーマル ユニバーシティ ピラゾロピリミジン化合物、医薬組成物、及びその使用
CN111718350B (zh) * 2019-03-19 2021-04-13 华中师范大学 吡唑取代的吡唑并嘧啶化合物和药物组合物及其应用
MX2021013576A (es) * 2019-05-08 2021-12-15 Tyk Medicines Inc Compuesto utilizado como inhibidor de la quinasa y aplicación del mismo.
CN114437077B (zh) * 2020-11-04 2024-01-30 浙江同源康医药股份有限公司 用作激酶抑制剂的化合物及其应用

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005066177A1 (fr) * 2003-12-31 2005-07-21 Schering-Plough Ltd. Lutte contre les parasites chez des animaux, a l'aide de derives d'imidazo[1,2-b]pyridazine
WO2007013673A1 (fr) * 2005-07-29 2007-02-01 Astellas Pharma Inc. Hétérocycles fusionnés en tant qu’inhibiteurs de lck

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3542661A1 (de) * 1985-12-03 1987-06-04 Bayer Ag Imidazopyridazinalkensaeureamide, verfahren zu ihrer herstellung, zwischenprodukte zu ihrer herstellung
KR100389192B1 (ko) * 1997-04-25 2003-06-27 다케다 야쿠힌 고교 가부시키가이샤 축합 피리다진 유도체, 그것의 제조 방법 및 용도
SE9800835D0 (sv) * 1998-03-13 1998-03-13 Astra Ab New Compounds
DE60037455T2 (de) * 1999-09-17 2008-11-27 Abbott Gmbh & Co. Kg Kinaseinhibitoren als arzneimittel
AU3740101A (en) * 2000-03-01 2001-09-12 Janssen Pharmaceutica Nv 2,4-disubstituted thiazolyl derivatives
GB0103926D0 (en) * 2001-02-17 2001-04-04 Astrazeneca Ab Chemical compounds
AU2003297161B8 (en) * 2002-12-18 2011-03-31 Vertex Pharmaceuticals Incorporated Triazolopyridazines as protein kinases inhibitors

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005066177A1 (fr) * 2003-12-31 2005-07-21 Schering-Plough Ltd. Lutte contre les parasites chez des animaux, a l'aide de derives d'imidazo[1,2-b]pyridazine
WO2007013673A1 (fr) * 2005-07-29 2007-02-01 Astellas Pharma Inc. Hétérocycles fusionnés en tant qu’inhibiteurs de lck

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
Annex 1 *
Annex 2 (Part 1) *
Annex 2 (Part 2) *
Appendix A *
Certified copy of the priority document PCT/JP2006/315346 *

Also Published As

Publication number Publication date
CA2620534C (fr) 2014-05-27
CA2620534A1 (fr) 2007-03-08
WO2007025540A3 (fr) 2007-05-18
JP5680824B2 (ja) 2015-03-04
WO2007025540A2 (fr) 2007-03-08
DE102005042742A1 (de) 2007-03-08
JP2009506993A (ja) 2009-02-19

Similar Documents

Publication Publication Date Title
EP2176266A2 (fr) Imidazo[1,2b]pyridazines substituees constituant des inhibiteurs de kinases, leur production et leur utilisation comme medicaments
EP1751118B1 (fr) Pyrimidines comme inhibiteurs de plk
DE60225563T2 (de) 4-amino-6-phenyl-pyrroloä2,3-düpyrimidin derivate
DE60316542T2 (de) 7-azaindole als inhibitoren c-jun n-terminaler kinasen zur behandlung neurodegenerativer störungen
EP1989198B1 (fr) Dérivés de 2,4-diaminopyrimidine pour le traitement et/ou la prévention de maladies cancéreuses, infectieuses, inflammatoires et autoimmunes
DE69938005T2 (de) Cyanophenyl-derivate
DE602004006169T2 (de) Substituierte 8'-pyri(mi)dinyl-dihydrospiro-äcycloalkylaminü-pyrimidoä1,2aüpyrimidin-6-onderivate
DE60302221T2 (de) Heteroaryl substituierte 2-pyridinyl und 2-pyrimidinyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-onderivate
WO2006131552A1 (fr) Alpha-carbolines comme inhibiteurs de cdk-1
JP2019523233A (ja) ムスカリン性アセチルコリンレセプターｍ４のポジティブアロステリック調節因子
CA2742322A1 (fr) Azepino[4,5-b]indoles et procedes pour leur utilisation
EP2041116A1 (fr) Dérivés d'hétéroaryle substitués par phényle et leur utilisation en tant qu'agents antitumoraux
JP4572195B2 (ja) ８−置換−６，７，８，９−テトラヒドロピリミド［１，２−ａ］ピリミジン−４−オン誘導体
JP4572194B2 (ja) 置換された８−パーフルオロアルキル−６，７，８，９−テトラヒドロピリミド［１，２−ａ］ピリミジン−４−オン誘導体
EP1902037A1 (fr) 2,4-diamino-pyrimidines comme inhibiteurs d'aurora
JP2011528025A6 (ja) 新規化学化合物
JP2011528025A (ja) 新規化学化合物
EP2090571A1 (fr) Derivés pyrimidine, agent pharamceutique contenant ces composés, utilisation et procédé de fabrication de ces composés
DE60209721T2 (de) Oxazolo- und furopyrimidine und deren verwendung als medikamente gegen tumore
EP1833830B1 (fr) Derive de quinoleine, son utilisation, sa fabrication et medicament le contenant
TW201014860A (en) New chemical compounds
EP3019493A1 (fr) Dihydroquinoxalinones et dihydropyridopyrazinones inhibitrices de protéine bet modifiées
WO1997032882A1 (fr) PYRIMIDO[5,4-d]PYRIMIDINES, MEDICAMENTS CONTENANT CES COMPOSES, LEUR UTILISATION ET LEUR PROCEDE DE PRODUCTION
DE60132531T2 (de) Pyridotriazine und Pyridopyridazine
EP1140096A1 (fr) Utilisation de derives de pyrimidine pour assurer la prophylaxie et la therapie de l'ischemie cerebrale

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20080222

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI SK TR

AX Request for extension of the european patent

Extension state: AL BA HR MK RS

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: BAYER PHARMA AKTIENGESELLSCHAFT

17Q First examination report despatched

Effective date: 20111222

DAX Request for extension of the european patent (deleted)
RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: BAYER INTELLECTUAL PROPERTY GMBH

TPAC Observations filed by third parties

Free format text: ORIGINAL CODE: EPIDOSNTIPA

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20160115