WO2006027366A1 - Derives de 1-deaza purine 2-substitues possedant une activite modulant le recepteur de l'adenosine - Google Patents

Derives de 1-deaza purine 2-substitues possedant une activite modulant le recepteur de l'adenosine Download PDF

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Publication number
WO2006027366A1
WO2006027366A1 PCT/EP2005/054405 EP2005054405W WO2006027366A1 WO 2006027366 A1 WO2006027366 A1 WO 2006027366A1 EP 2005054405 W EP2005054405 W EP 2005054405W WO 2006027366 A1 WO2006027366 A1 WO 2006027366A1
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Prior art keywords
amino
methyl
deazapurine
compound
disease
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PCT/EP2005/054405
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Melle Koch
Jacobus A.J. Den Hartog
Martinus J. Wanner
Gerrit-Jan Koomen
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Abbott Healthcare Products BV
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Solvay Pharmaceuticals BV
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Priority to CA002579303A priority Critical patent/CA2579303A1/fr
Priority to EP05789581A priority patent/EP1791841A1/fr
Publication of WO2006027366A1 publication Critical patent/WO2006027366A1/fr
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • 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
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • 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
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • 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
    • A61P25/08—Antiepileptics; Anticonvulsants
    • 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • 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
    • A61P25/24—Antidepressants
    • 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
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/06—Antiarrhythmics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Definitions

  • the present invention relates to 2-substituted-1-deaza purine derivatives as adenosine receptor modulating agents, to methods for the preparation of these compounds and to novel intermediates useful for the synthesis of said purine derivatives.
  • the invention also relates to the use of a compound disclosed herein for the manufacture of a medicament giving a beneficial effect.
  • a beneficial effect is disclosed herein or apparent to a person skilled in the art from the specification and general knowledge in the art.
  • the invention also relates to the use of a compound of the invention for the manufacture of a medicament for treating or preventing a disease or condition. More particularly, the invention relates to a new use for the treatment of a disease or condition disclosed herein or apparent to a person skilled in the art from the specification and general knowledge in the art.
  • specific compounds disclosed herein are used for the manufacture of a medicament useful in the treatment of disorders in which adenosine receptors are involved, or that can be treated via manipulation of those receptors.
  • Adenosine receptors At present, four types of adenosine receptors have been identified and designated A 1 , A 2A , A 2B and A 3 respectively. All four belong to the super -family of seven trans ⁇ membrane G-protein coupled receptors. Adenosine receptors are ubiquitous and involved in a great variety of biological processes. Thus, duri ng the past decades the therapeutic potential of adenosine receptor ligands has resulted in a substantial research interest.
  • 1-Deaza adenosines are known from EP 0 354 180 A, and were also descri -bed by J.E. Francis et al. (Canadian J. Chem. 70, 1288-1295, 1992) and MJ. Wanner et al. (Bioorganic & Medicinal Chemistry Letters 2000, 10, 2141 -2144). These compounds were shown to have affinity for adenosine receptors, notably for the adenosine A 2 receptor subtype, on which they are agonists.
  • the 1 -deaza adenosines described in the documents cited above all contain the 9- ⁇ -D-ribofuranosyl substituent characteristic for the natural ligand adenosine.
  • the goal of the present invention was to develop 1 -deazapurines without a ribose moiety, but with adenosine receptor modulating activity
  • Ri represents oxa-3-azabicyclo[2.2.2]oct-5-en-3-yl, 4-hydroxy-cyclohexyl- NH-, optionally substituted arylalkyl(Ci -3 )amines, cycloalkyl(C 3-8 )alkyl-
  • (Ci -3 )hydrazines - R 2 represents amino, NH-alkyl(Ci -3 ) or N-dialkyl(Ci -3 ) optionally substituted arylalkyl(Ci -3 )amines or cycloalkyl(C 3-8 )alkyl-(Ci -3 )amines, - R 3 represents hydrogen, alkyl(Ci -3 ) or arylalkyl(Ci -3 ) and tautomers, stereoisomers, prodrugs and salts thereof,
  • the invention relates to racemates, mixtures of diastereomers as well as the individual stereoisomers of the compounds having formula (1).
  • the invention also relates to the E isomer, Z isomer and E/Z mixtures of compounds having formula (1).
  • the abbreviation 'alkyl(d_ 3 )' means 'methyl, ethyl, n -propyl or isopropyl'.
  • Optionally substituted' means that a group may or may not be further substituted by one or more groups selected from alkyl, alkenyl, alkynyl, aryl, fluoro, chloro, bromo, hydroxyl, alkyloxy, alkenyloxy, aryloxy, acyloxy, amino, alkylamino, dialkylamino, arylamino, thio, alkylthio, arylthio, cyano, oxo, nitro, acyl, amido, alkylamido, dialkylamido, carboxyl, or two optional substituents may together with the carbon atoms to which they are attached form a 5- or 6-membered aromatic or non -aromatic ring containing 0, 1 or 2 heteroatoms selected from nitrogen, oxygen or sulphur.
  • 'alkyl' means d- 3 -alkyl
  • 'alkenyl' means Ci- 3 -alkenyl
  • 'alkynyl' means Ci -3 -alkynyl
  • 'acyl' means Ci -3 -acyl and 'aryl' means furyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1 ,3,5-triazynyl, phenyl, indazolyl, indolyl, indolizinyl, isoindolyl, benzi[b]furanyl, benzo[b]thiophenyl, benzimidazolyl, benzthiazolyl,
  • Optional substituents may themselves bear additional optional substituents.
  • Preferred optional substituents include Ci -3 alkyl such as for example methyl, ethyl, and trifluoromethyl, fluoro, chloro, bromo, hydroxyl, Ci -3 alkyloxy such as for example methoxy, ethoxy and trifluoromethoxy, and amino.
  • Prodrugs are therapeutic agents which are inactive per se but are transformed into one or more active metabolites. Prodrugs are bioreversible derivatives of drug molecules used to overcome some barriers to the utility of the parent drug molecule.
  • barriers include, but are not limited to, solubility, permeability, stability, presystemic metabolism and targeting limitations (Medicinal Chemistry: Principles and Practice, 1994, ISBN 0-85186-494-5, Ed.: F. D. King, p. 215; J. Stella, "Prodrugs as therapeutics", Expert Opin. Ther. Patents, 14(3), 277-280, 2004; P. Ettmayer et al., "Lessons learned from marketed and investigational prodrugs", J.Med.Chem., 47,
  • Pro-drugs i.e. compounds which when administered to humans by any known route, are metabolised to compounds having formula (1), belong to the invention.
  • this relates to compounds with primary or secondary amino or hydroxy groups.
  • Such compounds can be reacted with organic acids to yield compounds having formula (1) wherein an additional group is present which is easily removed after administration, for instance, but not limited to amidine, enamine, a Mannich base, a hydroxyl -methylene derivative, an O-(acyloxymethylene carbamate) derivative, carbamate, ester, amide or enaminone.
  • the invention particularly relates to compounds of the general formula (1) in which :
  • R 2 represents amino and R 3 represents methyl and tautomers, stereoisomers and salts thereof.
  • salts may be obtained using standard procedures well known in the art, for example by mixing a compound of the presen t invention with a suitable acid, for instance an inorganic acid such as hydrochloric acid, or with an organic acid.
  • a suitable acid for instance an inorganic acid such as hydrochloric acid, or with an organic acid.
  • the compounds of the invention of the general formula (1), as well as the salts thereof, have adenosine receptor modulating activity. They are useful in the treatment of disorders in which adenosine receptors are involved, or that can be treated via manipulation of those receptors.
  • inflammatory diseases including, arthritis, multiple sclerosis, asthma and psoriasis; gastro-intestinal disorders such as ulcers, inflammatory bowel disease (Crohn's disease) and ulcerative colitis; allergic responses such as eczema, atopic dermatitis and rhinitis; cardio-vascular disorders such as myocardial infarction, arrhythmias, hypertension, thrombosis, anaemia, arteriosclerosis, angina pectoris, cutaneous diseases such as urticaria, lupus erythematosus and pruritus; opthalmological disorders like glaucoma; respiratory disorders including chronic obstructive pulmonary disease, bronchitis and cystic fibrosis; central nervous system disorders including various forms of epilepsy, stroke, depression, sleep apnoea; disorders characterized by impairment of cognition and memory such as Alzheimer's disease, Creutzfeldt-Jacob disease, Huntington's disease, Parkinson'
  • the compounds of the invention can be brought into forms suitable for administration by means of usual processes using auxiliary substances such as liquid or solid carrier material.
  • the pharmaceutical compositions of the invention may be administered enterally, orally, parenterally (intramuscularly or intravenously), rectally or locally (topically). They can be administered in the form of solutions, powders, tablets, capsules (including microcapsules), ointments (creams or gel ) or suppositories.
  • Suitable excipients for such formulations are the pharmaceutically customary liquid or solid fillers and extenders, solvents, emulsifiers, lubricants, flavorings, colorings and/or buffer substances.
  • auxiliary substances which may be mentioned are magnesium carbonate, titanium dioxide, lactose, mannitol and other sugars or sugar alcohols, talc, lactoprotein, gelatin, starch, cellulose and its derivatives, animal and vegetable oils such as fish liver oil, sunflower, groundnut or sesame oil, polyethylene glycol and solvents such as, for example, sterile water and mono- or polyhydric alcohols such as glycerol.
  • Compounds of the present invention are generally administered as pharmaceutical compositions which are important and novel embodiments of the invention because of the presence of the compounds, more particularly specific compounds disclosed herein.
  • Types of pharmaceutical compositions that may be used include but are not limited to tablets, chewable tablets, capsules, sol utions, parenteral solutions, suppositories, suspensions, and other types disclosed herein or apparent to a person skilled in the art from the specification and general knowledge in the art.
  • the invention also includes the preparation or manufacture of sai d pharmaceutical compositions.
  • a pharmaceutical pack or kit comprising one or more containers filled with one or more of the ingredients of a pharmaceutical composition of the invention.
  • Associated with such con tainer(s) can be various written materials such as instructions for use, or a notice in the form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals products, which notice reflects approval by the agency of manufacture, use, or sale for human or veterinary administration.
  • Affinity of the compounds for human adenosine ⁇ receptors was determined using the receptor binding assay described by A. Townsend -Nicholson and P.R. Schofield (Biol. Chem., 269, 2373, 1994), using human recombinant receptors expressed in CHO cells, and [ 3 H]DPCPX as radioligand.
  • Affinity for human adenosine-A2A receptors was determined using the receptor binding assay described by A. Townsend -Nicholson and P.R. Schofield (Biol. Chem., 269, 2373, 1994), using human recombinant receptors expressed in CHO cells, and [ 3 H]DPCPX as radioligand.
  • Affinity of the compounds for human adenosine-A 2 A receptors was determined using the receptor binding assay described by D. R. Luthin et al. (Mol. Pharmacol. ,47, 307, 1995), using human recombinant receptors expressed in HEK-293 cells, and [ 3 H]CGS 21680 as radioligand.
  • Affinity of the compounds for human adenosine-A 2B receptors was determined using the receptor binding assay described by J. H. Stehle et al. (MoI. Endocrinol., 6, 384, 1992), using human recombinant receptors expressed in HEK-293 cells, and [ 3 H]MRS 1754 as radioligand.
  • Affinity of the compounds for human adenosine-A 3 receptors was determined using the receptor binding assay described by CA. Salvatore et al.: "Molecular cloning and characterization of the human A 3 adenosine receptor", Proc. Natl. Acad. Sci. USA, 90, 10365-10369, 1993. Briefly, membrane preparations were obtained from human recombinant (HEK 293) cells in which the human adenosine-A 3 receptor was stably expressed. Membranes were incubated at 22 0 C for 90 minutes with [ 125 I]-AB-MECA in the absence or presence of testcompounds in a concentration range from 10 ⁇ M down to 0.1 nM, diluted in a suitable buffer.
  • pKi -log (IC 50 / (1+ S/K d ) ) in which the IC 50 is as described above, S is the concentration [ 125 I]-AB-MECA used in the assay expressed in mol/l (typically 0.1 nM), and K d is the equilibrium dissociation constant of [ 125 I]-AB-MECA for human adenosine-A 3 receptor s (0.22 nM).
  • the compounds of the invention have affinity for at least one of the adenosine receptors in one of the binding assays described above. These properties make them useful in the treatment of disorders in which adenosine receptors are involved, or that can be treated via manipulation of these receptors.
  • the affinity of the compounds of the invention for adenosine A 3 receptors was determined as described above. From the binding affinity measured for a given compound of formula (1), one can estimate a theoretical lowest effective dose. At a concentration of the compound equal to twice the measured Kj-value, nearly 100% of the adenosine A 3 receptors likely will be occupied by the compound. Converting that concentration to mg of compound per kg of patient yields a theoretical lowest effective dose, assuming ideal bioavailability. Pharmacokinetic, pharmacodynamic, and other considerations may alter the dose actually administered to a higher or lower value. The dosage expediently administered is 0.001 - 1000 mg/kg, preferably 0.1 -100 mg/kg of patient's bodyweight.
  • treatment refers to any treatment of a human condition or disease and includes: (1) preventing the disease or condition from occurring in a subject which may be predisposed to the disease but has not yet been diagnosed as having it, (2) inhibiting the disease or condition, i.e., arresting its development, (3) relieving the disease or condition, i.e., causing regression of the condition, or (4) relieving the conditions caused by the disease, i.e., stopping the symptoms of the disease.
  • Nuclear magnetic resonance spectra ( 1 H NMR and 13 C NMR, APT) were determined in the indicated solvent using a Bruker ARX 400 ( 1 H: 400 MHz, 13 C: 100 MHz) at 300 K, unless indicated otherwise.
  • 19 F NMR and 13 C NMR experiments were carried out on a Varian Inova 500 spectrometer operating at 11.74 T (499.9 MHz for 1 H; 125.7 MHz for 13 C; 50.7 Mhz, 470.4 MHz for 19 F) using a 5 mm SW probe.
  • the spectra were determined in deuterated chloroform or dichloromethane obtained from Cambridge Isotope Laboratories Ltd.
  • Mass spectra and accurate mass measurements were performed using a JEOL JMS - SX/SX 102 A Tandem Mass Spectrometer using Fast Atom Bombardement (FAB). A resolving power of 10,000 (10% valley definition) for high resolution FAB mass spectrometry was used. Extinction coefficients were determined with a HP 8453 UV- Vis spectrophotometer.
  • Adenosine receptor affinity data obtained according to the protocols given above are shown in the table below.

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Abstract

La présente invention concerne des dérivés de 1-deaza purine 2-substitués, utilisés comme agents modulant le récepteur de l'adénosine, ainsi que leurs méthodes de préparation et de nouveaux produits intermédiaires pouvant être utilisés pour la synthèse de ces dérivés de purine. Ces composés sont représentés par la formule générale (1) dont les symboles désignent des éléments définis dans la description de la présente demande.
PCT/EP2005/054405 2004-09-09 2005-09-07 Derives de 1-deaza purine 2-substitues possedant une activite modulant le recepteur de l'adenosine Ceased WO2006027366A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
CA002579303A CA2579303A1 (fr) 2004-09-09 2005-09-07 Derives de 1-deaza purine 2-substitues possedant une activite modulant le recepteur de l'adenosine
EP05789581A EP1791841A1 (fr) 2004-09-09 2005-09-07 Dérivés de 1-deaza purine 2-substitués à activité modulatrice du recepteur d'adénosine

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US60814504P 2004-09-09 2004-09-09
US60/608,145 2004-09-09
EP04104345.6 2004-09-09
EP04104345 2004-09-09

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WO2006027366A1 true WO2006027366A1 (fr) 2006-03-16

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AR (1) AR050860A1 (fr)
CA (1) CA2579303A1 (fr)
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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007022305A3 (fr) * 2005-08-16 2007-04-12 Pharmacopeia Drug Discovery 2-aminoimidazopyridines destinees a traiter des maladies neurodegeneratives
US7338964B2 (en) 2004-09-09 2008-03-04 Solvay Pharmaceuticals, B.V. 2-substituted-1-deaza purine derivatives with adenosine receptor modulating activity
US7371737B2 (en) 2004-09-09 2008-05-13 Solvay Pharmaceuticals, B.V. 2-substituted-6-trifluoromethyl purine derivatives with adenosine-A3 antagonistic activity
US7462534B2 (en) 2005-08-02 2008-12-09 Micron Technology, Inc. Methods of forming memory circuitry
WO2009034411A1 (fr) * 2007-09-12 2009-03-19 Centre National De La Recherche Scientifique Perharidines en tant qu'inhibiteurs de cdk

Citations (1)

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Publication number Priority date Publication date Assignee Title
EP0354180A2 (fr) * 1988-08-02 1990-02-07 Ciba-Geigy Ag Certains dérivés imidazo(4,5b)pyridiniques

Patent Citations (1)

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Publication number Priority date Publication date Assignee Title
EP0354180A2 (fr) * 1988-08-02 1990-02-07 Ciba-Geigy Ag Certains dérivés imidazo(4,5b)pyridiniques

Non-Patent Citations (6)

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FRANCIS, JOHN E. ET AL: "A general synthesis of 5,7-diaminoimidazo[4,5-b]pyridine ribosides (2-amino-1-deazaadenosines) from 5-amino-4-imidazolecarboxamide riboside (AICA riboside)", CANADIAN JOURNAL OF CHEMISTRY , 70(5), 1288-95 CODEN: CJCHAG; ISSN: 0008-4042, 1992, XP009045697 *
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Cited By (7)

* Cited by examiner, † Cited by third party
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US7338964B2 (en) 2004-09-09 2008-03-04 Solvay Pharmaceuticals, B.V. 2-substituted-1-deaza purine derivatives with adenosine receptor modulating activity
US7371737B2 (en) 2004-09-09 2008-05-13 Solvay Pharmaceuticals, B.V. 2-substituted-6-trifluoromethyl purine derivatives with adenosine-A3 antagonistic activity
US7462534B2 (en) 2005-08-02 2008-12-09 Micron Technology, Inc. Methods of forming memory circuitry
WO2007022305A3 (fr) * 2005-08-16 2007-04-12 Pharmacopeia Drug Discovery 2-aminoimidazopyridines destinees a traiter des maladies neurodegeneratives
WO2009034411A1 (fr) * 2007-09-12 2009-03-19 Centre National De La Recherche Scientifique Perharidines en tant qu'inhibiteurs de cdk
WO2009034475A3 (fr) * 2007-09-12 2009-08-13 Centre Nat Rech Scient Imidazo[4,5b]pyridines
US8450342B2 (en) 2007-09-12 2013-05-28 Centre Nationale De La Recherche Scientifique Perharidines as CDK inhibitors

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AR050860A1 (es) 2006-11-29

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