EP2044071A1 - Imidazo[1,2b]pyridazine substituée par oxo, sa production et son utilisation en tant que médicament - Google Patents

Imidazo[1,2b]pyridazine substituée par oxo, sa production et son utilisation en tant que médicament

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Publication number
EP2044071A1
EP2044071A1 EP07726169A EP07726169A EP2044071A1 EP 2044071 A1 EP2044071 A1 EP 2044071A1 EP 07726169 A EP07726169 A EP 07726169A EP 07726169 A EP07726169 A EP 07726169A EP 2044071 A1 EP2044071 A1 EP 2044071A1
Authority
EP
European Patent Office
Prior art keywords
imidazo
pyridazine
phenyl
yloxy
pyridazin
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Withdrawn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
EP07726169A
Other languages
German (de)
English (en)
Inventor
Olaf Prien
Knut Eis
Benjamin Bader
Judith Guenther
Arne Bonin Von
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 EP2044071A1 publication Critical patent/EP2044071A1/fr
Withdrawn legal-status Critical Current

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    • 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
    • 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
    • A61P17/00—Drugs for dermatological disorders
    • 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
    • A61P19/00—Drugs for skeletal disorders
    • 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
    • A61P35/04—Antineoplastic agents specific for metastasis
    • 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
    • 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

  • the PKC family is divided into several isoforms.
  • a key role in the regulation of T-cell activation is the Ca 2+ -dependent isoform PKC- ⁇ . This is expressed selectively in the T cells and to a lesser extent in skeletal muscle cells (Meiler et al., 1998. New perspectives on PKC, a member of the novel subfamily of protein kinase C. Stern Cells 16: 178-192; Altman et al 2000. Protein kinase C ⁇ : a new essential fortunate on the T-cell stage, Immunol Today 21: 567-573; Arendt et al., 2002.
  • PKC- ⁇ Protein kinase C-theta: signaling from the center of the T Cell Synapse, Current Opinion in Immunology 14: 323-330. While 7 different PKC isoforms ( ⁇ , ⁇ , ⁇ , ⁇ , ⁇ , ⁇ and ⁇ ) are expressed in primary human T cells, only PKC- ⁇ (but not the other isoforms) shows the ability of the central transcription factors AP-1 and NF-kappaB to regulate.
  • PKC- ⁇ (but not other PKC isoforms) localizes into the center of the immunological synapse in so-called 'lipid rafts', directly following the transfer of the activation signal from the TCR to other target molecules of the T cell (via phosphorylation of these Molecule) to transcription factors (Baier-Bitterlich et al., 1996. Protein kinase C-theta isoenzyme selective stimulation of the transcription factor complex AP-1 in T lymphocytes., Mol. Cell. Biol. 16: 1842-1850; Lin et al., 2000.
  • Protein kinase C ⁇ participates in NF-kB activation induced by CD3-CD28 costimulation through selective activation of IkappaB kinase ⁇ . Mol. Cell. Biol. 20: 2933-2940; Coudronniere et al. 2000. NF-kB activation induced by T cell receptor / CD28 costimulation is mediated by protein kinase C- ⁇ . Proc. Natl. Acad. Be. USA 97: 3394-3399).
  • PKC- ⁇ due to this close link to the TCR signaling pathway, is an interesting molecule in the search for new therapeutic approaches to the regulation of the adaptive immune response.
  • T cells show a strongly non-reactive phenotype, including immunosuppression.
  • IL-2 as a key cytokine in the T cell response is formed only diminished.
  • the ability of T cells to proliferate is significantly inhibited.
  • 1 -3CrC ⁇ -alkyl or Cj-C ⁇ -cycloalkyl groups which are optionally substituted by 1 -3 hydroxy and / or 1 -3 halogen or cyano groups and / or 1 -3 (C 1 -C 5 ) - alkoxy groups and / or 1 -3 COOR 6 groups and / or 1 -3 NHR 6 groups and / or 1 -3 NHCOR 6 groups and / or 1 -3 N (R 2 ) 2 groups substituted or interrupted by 1 -3 keto groups can,
  • 1 -3 CrC ⁇ fluoroalkyl which is optionally substituted by 1 -3 hydroxy and / or 1 -3 optionally fluorinated (Ci-Cs) -alkoxy groups and / or 1 -3 COOR 2 groups can be substituted,
  • R 2 are each independently
  • a hydrogen atom a phenyl radical, an optionally partially or fully fluorinated dC 5 alkyl radical or
  • each R 6 is independently either
  • aryl or heteroaryl radical which in turn can be substituted independently of one another by 1 -3-fold with hydroxyl radicals, halogen atoms, cyano groups and / or C 1 -C 5 -alkoxy radicals,
  • Hydroxy groups may also be condensed with aldehydes or ketones or halogenated aldehydes or halogenated ketones,
  • n is a number 2-6, and wherein R 3 and R 4 independently represent a hydrogen atom, a -COR 6 radical, a
  • a - (CH 2 ) t -Z- (CH 2 ) m -NR 3 R 4 radical wherein Z represents a group -O-, -S-, -NR 2 -, -CHR 5 - or -C (R 5 ) 2 -, m is a number O, 1 or 2, t is a number O, 1, 2 or 3 and in which R 3 and R 4 have the abovementioned meaning, and R 5 is a C 1 -C 3 - Alkyl, C 2 -C 3 -alkenyl, C 2 -C 3 -alkynyl, a phenyl or a C 3 -C 6 -cycloalkyl radical,
  • n is a number 1 -6 and wherein R 7 and R 8 together form a 3-7 membered ring, which 3-7 membered ring may contain another heteroatom and wherein the 3-7 membered ring is optionally 1 -3 times with a halogen atom, a hydroxy group, a cyano group, a nitro group, a group -R 6 , a group -NHR 2 , a group -N (R 2 ) 2 , a group -CO 2 R 6 , a group -OCOR 6 of a group -SO 2 R 2 or a group -OR 2 is substituted or by 0-3
  • Keto groups is interrupted,
  • a - (CH 2 ), - Y 1 radical wherein r is a number 0-3 and Y 1 is a piperidine or pyrrolidine ring, wherein the piperidine or pyrrolidine ring optionally 1 -3 times independently of one another with a halogen atom one
  • a - (CH 2) r -Y 3 radical where r is a number 0-3, and Y 3 represents a piperazine ring, the nitrogen atom at an optional -C 3 alkyl or C 1 -C 3 -
  • Acyl group carries, wherein the piperazine ring optionally 1 -3 times with a halogen atom, a hydroxy group, a cyano group, a
  • a - (CH 2 ) r -Y 4 radical wherein r is a number 0-3 and Y 4 is a C 3 -Cs -cycloalkyl ring optionally containing 1 -3 times with a halogen atom, a hydroxy group, a cyano group , a nitro group, a group -R 6 , a group -NHR 2 , a group -N (R 2 J 2 , a group -CO 2 R 6 , a group -OCOR 6 of a group -SO 2 R 2 or a group - OR 2 is substituted,
  • 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 and hexyl to understand.
  • alkyl radical such as, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec. Butyl, tert. Butyl, pentyl, isopentyl, neopentyl and hexyl to understand.
  • fluoroalkyl is in each case a straight-chain or branched alkyl radical in which at least one hydrogen atom is replaced by a fluorine atom, for example fluoromethyl, difluoromethyl, trifluoroethyl, trifluoroethyl, pentafluoroethyl, perfluoropropyl and perfluoroisopropyl.
  • Alkoxy is in each case a straight-chain or branched alkoxy radical, such as, for example, methyloxy, ethyloxy, propyloxy, isopropyloxy, butyloxy, isobutyloxy, sec. Butyloxy, pentyloxy, isopentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy or decyloxy.
  • alkoxy radical such as, for example, methyloxy, ethyloxy, propyloxy, isopropyloxy, butyloxy, isobutyloxy, sec. Butyloxy, pentyloxy, isopentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy or decyloxy.
  • Alkynyl is in each case to be understood as meaning a straight-chain or branched alkynyl radical which contains 2-6, preferably 2-4, C atoms.
  • the following radicals may be mentioned by way of example: acetylenyl, propyn-1-yl, propyn-3-yl (propargyl), but-1-yn-1-yl, but-1-yn-4-yl, but-2-yn 1 -yl, but-1-yn-3-yl, 3-methylbut-1-yn-3-yl.
  • C 3 -C 6 -cycloalkyl represents an alkyl ring comprising 3 to 6 carbon atoms, which may optionally contain one or more double bonds in the ring.
  • the term "independently of one another" means that multiple substituents may be different from each other, for example, the compound contains 3- (3-chloro-4-fluoro-phenyl) -6- [3- (4-methylpiperazin-1-yl) -propoxy] -imidazo [1, 2 b] pyridazines have a phenyl ring substituted by two halogen atoms, but the halogen atoms are different from each other (fluorine and chlorine).
  • Q is an aryl or heteroaryl radical which may be linked at any position with the imidazo [1,2b] pyridazine radical. It is clear to the person skilled in the art that all synthetically accessible aryl or heteroaryl compounds which are stable under physiological conditions are meant.
  • Preferred radicals Q are the phenyl, thiophenyl, biphenyl, furanyl, benzofuranyl, indolyl, pyridinyl, benzothiophenyl and the naphthalenyl group.
  • substituents in Q are cyclopropylmethoxy, fluoro, chloro, hydroxy, cyano, trifluoromethyl, trifluoromethoxy, methyl, methoxy, pyrrolidinyl, -CO-OCH 3 , -CO-CH 3 , -CO 2 H , -CO-NH 2 , -CH 2 -CN, -CH 2 -OH, -CH 2 -S-CH 3 , -S-CH 3 , -SO 2 -CH 2 CH 3 or -NHCOCH 3 .
  • a preferred class of compounds of general formula I is formed by those in which R 1 is
  • R 1 is a - (CH 2 ) n -NR 3 R 4 radical, where n is 3 or 4 and in which R 3 and R 4 independently of one another are a C 1 -C 3 alkyl radical.
  • R 1 is a - (CH 2 J n -NR 7 R 8 radical, where n is 3 or 4 and in which R 7 and R 8 together form a 5-7 membered ring.
  • the compounds of the invention may also be present in the form of salts with pharmacologically acceptable cations or anions, for example in the form of the sodium salt, potassium salt, magnesium salt, ammonium salt, N-methyl-glucamine salt, N, N-dimethyl-glucamine salt, hydrochloride, sulfate, nitrate , Phosphates, Pivalates, Maleates, Fumarates, Tartrates, Benzoates, Mesylates, Citrates or Succinates.
  • salts with pharmacologically acceptable cations or anions for example in the form of the sodium salt, potassium salt, magnesium salt, ammonium salt, N-methyl-glucamine salt, N, N-dimethyl-glucamine salt, hydrochloride, sulfate, nitrate , Phosphates, Pivalates, Maleates, Fumarates, Tartrates, Benzoates, Mesylates, Citrates or Succinates.
  • Compounds of the invention are useful as kinase inhibitors, particularly tyrosine and serine / threonine kinases.
  • the compounds of the general formula I according to the invention are, inter alia, inhibitors of the protein kinase C family, such as, for example, PKC theta, delta, iota, alpha and zeta.
  • An inhibitor of a kinase can therefore be used, on the one hand, to study the functional mechanisms of the kinase, in particular the investigation of a disease which is based on a malfunction of the kinase. But also a due to the malfunction of the kinase disease can be treated or prevented with the kinase inhibitor.
  • the invention therefore furthermore relates to the use of a compound of the general formula I according to the invention for the preparation of a pharmaceutical composition, in particular for inhibiting a cellular kinase, preferably kinases of the protein kinase (PK) family and in particular for inhibiting kinases of the PKC subfamily, especially for the inhibition of PKC theta kinase, or for the treatment or prophylaxis of a Disease which is associated with the overexpression or mutation of a cellular kinase, in particular such a cellular kinase.
  • diseases are, in particular, inflammatory diseases, oncological diseases and autoimmune diseases.
  • the compounds according to the invention are likewise suitable for the preparation of compounds for immunosuppression.
  • the compounds according to the invention are particularly suitable for the preparation of medicaments for the treatment of type II diabetes, asthma, dermatitis, psoriasis, rheumatoid arthritis, contact dermatitis, atopic dermatitis, contact allergy, multiple sclerosis, inflammatory bowel diseases or transplant rejections.
  • the present compounds can also be used for the modulation of an immune reaction, for example after transplantation to avoid organ rejection.
  • a pharmaceutical composition according to the invention can be prepared by mixing a physiologically effective dose of a compound according to the invention with at least one galenic excipient and preparing it into a desired administration form.
  • a physiologically effective dose for example, an amount of 1 to 1000 mg, in particular from 50 to 500 mg, per administration unit per day for a 75 kg human in question, where the dose given as a single dose to be administered or divided into 2 or more daily doses can be.
  • the galenic preparation of a pharmaceutical composition according to the invention can be carried out in the usual way.
  • kinase is accompanied, wherein a pharmaceutical composition containing a physiologically effective dose of a compound of general formula I a
  • Preferred compounds of formula IIb are 3-bromo-6- (3-morpholin-4-yl-propoxy) imidazo [1,2-b] pyridazine, 3-bromo-6- (3-piperidine-1-yl-propoxy ) -imidazo [1,2b] pyridazine, 3-bromo-6- [2- (1-methyl-pyrrolidin-2-yl) -ethoxy] -imidazo [1,2-bpyridazine, 3-bromo-6- (1-methyl-piperidin-3-ylmethoxy) -imidazo [1,2-b] pyridazine, 3-bromo-6- (1-ethyl-pyrrolidin-3-yloxy) -imidazo [1,2-b] pyridazine, [3- (3-Bromoimidazo [1,2-b] pyridazin-6-yloxy) -propyl] -diethyl-amine, 3-bromo-6- [3- (4
  • reaction mixture is mixed with water and after addition of saturated sodium bicarbonate solution, the phases were separated.
  • the aqueous phase was extracted three more times with ethyl acetate. Thereafter, the combined organic phases were washed once each with saturated sodium dithionite.
  • reaction mixture is mixed with saturated sodium chloride solution.
  • aqueous phase is extracted with ethyl acetate.
  • the organic phase is washed twice with dilute aqueous NaCl solution and once with saturated aqueous NaCl solution and dried over sodium sulfate.
  • the final chromatographic purification on silica gel isolated 2.78 g (40%) of the desired product.
  • the reaction mixture thus obtained is washed with sat. aqueous ammonium chloride solution and extracted with ethyl acetate.
  • the organic phase is washed with sat. aqueous sodium chloride solution. washed, dried over sodium sulfate and the solvent evaporated.
  • the final chromatographic purification on silica gel isolated 3.46 g (73%) of the desired product.
  • reaction mixture was treated with water and ethyl acetate and after addition of saturated sodium bicarbonate solution, the phases were separated.
  • the aqueous phase was extracted three more times with ethyl acetate. Thereafter, the combined organic phases were washed with sat. Washed sodium chloride solution and dried over sodium sulfate. The final chromatographic purification on silica gel yielded 1.36 g (40%) of the desired product.
  • the mixture was mixed with saturated sodium bicarbonate solution, diluted with water.
  • the aqueous phase was extracted three more times with ethyl acetate. Thereafter, the combined organic phases were washed once with saturated sodium chloride solution and dried over sodium sulfate.
  • the final chromatographic purification of the crude product on silica gel isolated 200 mg (17%) of the desired product.
  • the preparation of the end compounds according to the invention can also be carried out by parallel synthesis, for example in an automatic synthesizer.
  • Example 2 6- [3- (4-Methyl-piperazin-1-yl) -propoxy] -3-thiophen-2-yl-imidazo [1,2-b] pyridazine
  • test substances (0 ⁇ M and 10 measurement points within the range 0.001-20 ⁇ M in duplicate) in assay buffer [50 mM Hepes NaOH pH 7.4, 1.0 mM MnCl 2 , 10.0 mM MgCl 2 , 1.0 mM dithiothreitol, 0.1 mM sodium orthovanadate, 10 ⁇ M adenosine tri-phosphate (ATP), 0.5 ⁇ M substrate peptide, 0.1 mg / ml phosphatidylserine, 0.01 mg / ml diacylglycerol, 1% (v / v) dimethylsulfoxide].
  • assay buffer 50 mM Hepes NaOH pH 7.4, 1.0 mM MnCl 2 , 10.0 mM MgCl 2 , 1.0 mM dithiothreitol, 0.1 mM sodium orthovanadate, 10 ⁇ M adenosine tri-phosphate (ATP), 0.5 ⁇ M

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Diabetes (AREA)
  • Pulmonology (AREA)
  • Dermatology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Oncology (AREA)
  • Transplantation (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne de nouveaux inhibiteurs de kinases de formule (I), dans laquelle Q et R<SUP>1</SUP> sont tels que définis dans les revendications, des procédés de production de ces inhibiteurs, des produits intermédiaires pour réaliser ces inhibiteurs et des utilisations de ces inhibiteurs.
EP07726169A 2006-06-21 2007-06-20 Imidazo[1,2b]pyridazine substituée par oxo, sa production et son utilisation en tant que médicament Withdrawn EP2044071A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102006029447A DE102006029447A1 (de) 2006-06-21 2006-06-21 Oxo-substituierte Imidazo[1,2b]pyridazine, deren Herstellung und Verwendung als Arzneimittel
PCT/EP2007/005697 WO2007147646A1 (fr) 2006-06-21 2007-06-20 Imidazo[1,2b]pyridazine substituée par oxo, sa production et son utilisation en tant que médicament

Publications (1)

Publication Number Publication Date
EP2044071A1 true EP2044071A1 (fr) 2009-04-08

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Country Status (6)

Country Link
US (2) US8653076B2 (fr)
EP (1) EP2044071A1 (fr)
JP (1) JP5583968B2 (fr)
CA (1) CA2656413C (fr)
DE (1) DE102006029447A1 (fr)
WO (1) WO2007147646A1 (fr)

Families Citing this family (28)

* Cited by examiner, † Cited by third party
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DE102006029447A1 (de) * 2006-06-21 2007-12-27 Bayer Schering Pharma Ag Oxo-substituierte Imidazo[1,2b]pyridazine, deren Herstellung und Verwendung als Arzneimittel
BRPI0718029A2 (pt) * 2006-11-06 2013-11-26 Supergen Inc Derivados de imidazo(1,2-b)piridazina e pirazolo(1,5-a)pirimidina e seu uso como inibidores da proteína cinase
JP2013518112A (ja) * 2010-01-27 2013-05-20 バーテックス ファーマシューティカルズ インコーポレイテッド ピラゾロピリジンキナーゼ阻害剤
EP2528917B1 (fr) * 2010-01-27 2016-10-19 Vertex Pharmaceuticals Incorporated Pyrazolopyridines utiles dans le traitement de maladies auto-immunes, inflammatoires ou (hyper)proliferatives
GB201002911D0 (en) * 2010-02-19 2010-04-07 Medical Res Council Compound
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CA2836203A1 (fr) 2011-05-17 2012-11-22 Bayer Intellectual Property Gmbh Imidazopyridazines amino-substituees en tant qu'inhibiteurs de kinase mknk1
WO2012163942A1 (fr) 2011-06-01 2012-12-06 Bayer Intellectual Property Gmbh Aminoimidazopyridazines substituées
US9284319B2 (en) 2011-06-22 2016-03-15 Bayer Intellectual Property Gmbh Heterocyclyl aminoimidazopyridazines
EP2734205B1 (fr) 2011-07-21 2018-03-21 Tolero Pharmaceuticals, Inc. Inhibiteurs de protéine kinase hétérocycliques
UA117092C2 (uk) * 2011-09-06 2018-06-25 Байєр Інтеллектуал Проперті Гмбх Амінозаміщені імідазопіридазини
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JP6147761B2 (ja) * 2011-12-12 2017-06-14 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 アミノ置換イミダゾピリダジン
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CN105164124B (zh) 2012-11-19 2017-03-15 诺华股份有限公司 用于治疗寄生虫疾病的化合物和组合物
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JP5583968B2 (ja) 2014-09-03
CA2656413C (fr) 2016-08-02
US20090093475A1 (en) 2009-04-09
US20140135323A1 (en) 2014-05-15
JP2009541241A (ja) 2009-11-26
WO2007147646A1 (fr) 2007-12-27
CA2656413A1 (fr) 2007-12-27
DE102006029447A1 (de) 2007-12-27

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