WO2001025237A1 - Nouveaux composes imidazopyridine carbonitrile - Google Patents

Nouveaux composes imidazopyridine carbonitrile Download PDF

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WO2001025237A1
WO2001025237A1 PCT/SE2000/001860 SE0001860W WO0125237A1 WO 2001025237 A1 WO2001025237 A1 WO 2001025237A1 SE 0001860 W SE0001860 W SE 0001860W WO 0125237 A1 WO0125237 A1 WO 0125237A1
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alkyl
imidazopyridine
carbon atoms
compound according
carbonitrile
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PCT/SE2000/001860
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English (en)
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Margareta HERSLÖF
Peter Nordberg
Henrik Sörensen
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Astrazeneca Ab
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Priority to JP2001528181A priority Critical patent/JP2003511381A/ja
Priority to EP00970372A priority patent/EP1222188A1/fr
Priority to CA002385251A priority patent/CA2385251A1/fr
Priority to AU79764/00A priority patent/AU7976400A/en
Publication of WO2001025237A1 publication Critical patent/WO2001025237A1/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
    • 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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • 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
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • 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
    • 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
    • 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
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
    • 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

Definitions

  • the present invention relates to a selective inhibitor of mammalian osteoclast cell activity, processes for its preparation and pharmaceutical compositions comprising the same as well as methods of treatment, where said selective inhibitor is administered to a human or animal patient. More specifically, the present invention relates to a selective inhibitor of vacuolar H + -ATPase in mammalian osteoclast cells.
  • the third subtype i.e. "a3" (EMBL accession number U45285), has been cloned from a human osteoclastoma cDNA library and suggested to be an osteoclast-specific isoform of "a” (Li, Y. P., Chen, W. and Stashenko, P., Biochemical & Biophysical Research Communications, 218(3), 813-21 (1996)).
  • novel compounds with excellent therapeutical effect against physiological disorders involving ter alia bone resorption have now been found. More specifically, said compounds comprise a selective inhibitor of mammalian osteoclast cell activity, wherein said inhibitor comprises an imidazopyridine carbonitrile compound. Since the selective inhibitor of the present invention has been found to inhibit vacuolar H + - ATPase, such as vacuolar H + - ATPase in osteoclast cells, it is thereby therapeutically efficient against physiological disorders involving bone resorption.
  • said imidazopyridine carbonitrile compound has the general formula I:
  • R ⁇ is selected from the group consisting of
  • Rj+ R2 form a five membered ring containing at least one O, S and or N;
  • R2 is selected from the group consisting of (a) H;
  • Rg and R9 are either independently selected from the group consisting of H; a straight chain, branched or cyclic saturated or unsaturated alkyl having 1-6 carbon atoms, optionally substituted with O-alkyl, NH-alkyl, N-dialkyl, N- pyrrolidinyl, N-piperidinyl, N-morpholinyl or N-piperazinyl; and aryl selected from the group consisting of phenyl, imidazolyl, pyridinyl or pyrrolyl; or together form a five or six membered saturated or unsaturated ring, optionally containing O, S, and/or N;
  • R3-R7 are selected from the group consisting of (a) H
  • R2 is S-Me, NRgRc), O-alkyl or alkyl having 1-6 carbon atoms; R1 , R3 and R4 are H; and R5, R5 and R7 are straight chain, branched or cyclic saturated or unsaturated O-alkyl having 1-3 carbon atoms.
  • R2 is S-Me, NRgRc), O-alkyl or alkyl having 1-6 carbon atoms; R1 , R3, R4, R5 are H; and Rg and R7 are straight chain, branched or cyclic saturated or unsaturated O-alkyl having 1-3 carbon atoms.
  • R2 is S-Me, NRgRtj, O-alkyl or alkyl having 1 -6 carbon atoms
  • R1 , R3, R5, R6, R7 are H
  • R4 is straight chain, branched or cyclic saturated or unsaturated O-alkyl having 1-3 carbon atoms.
  • said imidazopyridine carbonitrile compound is selected from the group consisting of:
  • the present invention also relates to a process for the preparation of an imidazopyridine carbonitrile compound according to any one of the embodiments set forth above.
  • a suitably substituted amino-nicotinonitrile is heated with an ⁇ -halosubstituted carbonyl reagent under basic conditions, optionally in the presence of a solvent, during 2-24 h.
  • a suitably substituted l,3-diphenyl-propane-l,3-dione and a suitably substituted (lH-benzimidazol-2-yl)-acetonitrile are treated with an alkali metal alkoxide and refluxed in an alcohol during 2-12 h.
  • Scheme 1 illustrates general synthetic pathways for the preparation of the imidazopyridine carbonitrile compounds of the present invention.
  • the synthesis of suitable starting materials is readily accomplished by a person skilled in the art.
  • Procedure 1 Appropriate amounts of a suitably substituted amino-nicotinonitrile and an ⁇ - halosubstituted carbonyl reagent are heated under basic conditions, e.g. in the presence of NaHCO3, in a suitable solvent, such as e.g. ethanol, butanol or chloroform, for about 2-24 h. After evaporation, dilution with CH2CI2, washing with brine and drying, the solvent is removed. The residue is purified either by recrystallisation or chromatography on silica gel. From this procedure, substituted 5,7-diphenyl-imidazo[l,2-a]pyridine-8-carbonitrile is isolated.
  • a suitable solvent such as e.g. ethanol, butanol or chloroform
  • Procedure 2 (especially for compounds, where R 9 and Rio are part of a benzene ring): Appropriate amounts of a suitably substituted l,3-diphenyl-propane-l,3-dione and a suitably substituted (lH-benzimidazol-2-yl)-acetonitrile are treated with an alkali metal alkoxide, such as NaOEt, and refluxed in an alcohol for 2-12 h. The imidazopyridine carbonitrile compound is isolated as in procedure 1.
  • the present invention relates to an imidazopyridine carbonitrile compound with the general formula I for use as a pharmaceutical.
  • the present invention also relates to a pharmaceutical composition
  • a pharmaceutical composition comprising an imidazopyridine carbonitrile compound according to any one of the embodiments set forth above as active ingredient in association with a pharmaceutically acceptable adjuvant, diluent or carrier.
  • the amount of said active ingredient per dosage unit is generally within the range of about 1 to 1 000 mg preferably 1-300 mg.
  • the amount of said active ingredient is typically within the range of about 0.1 to 95% by weight of said pharmaceutical composition.
  • the present invention is also related to the use of an imidazopyridine carbonitrile compound according to any one of the previously outlined embodiments in the manufacture of a medicament for use in therapeutic or prophylactic treatment of a human or animal body.
  • said use is related to a medicament intended for treatment involving inhibition of vacuolar H+- ATPase, preferably vacuolar H+- ATPase in osteoclast cells.
  • the medicament is intended for treatment involving inhibition of vacuolar H+- ATPase containing the isoform a3, said vacuolar H+- ATPase preferably being present in osteoclast cells.
  • said medicament is intended for treatment involving inhibition of bone reso ⁇ tion, or is intended for treatment and/or prevention of diseases related to increased bone reso ⁇ tion, preferably osteoporosis.
  • the medicament is intended for treatment of Paget's disease of bone, hype ⁇ arathyroidism, malignant neoplasms, parodontal diseases, prosthetic and/or implant related bone loss, tumours, AIDS and disorders related thereto, Alzheimer's disease, angiogenesis, atherosclerosis, rheumatoid arthritis, diabetic retinopathy, psoriasis or diabetes.
  • the present invention is also related to a method for inhibiting vacuolar H + - ATPase, preferably vacuolar H + - ATPase in osteoclast cells, or to a method for inhibiting vacuolar H + - ATPase containing the isoform a3, said vaculoar H+- ATPase preferably being present in osteoclast cells, wherein any one of said methods comprises administering to a human or animal patient a therapeutically effective amount of an imidazopyridine carbonitrile compound according to any one of the embodiments outlined above.
  • the present invention is related to a method for inhibiting bone reso ⁇ tion, or to a method for treatment and/or prevention of diseases related to increased bone reso ⁇ tion, preferably osteoporosis, wherein any one of said methods comprises administering to a human or animal patient a therapeutically effective amount of an imidazopyridine carbonitrile compound according to any one of the embodiments set forth above.
  • the present invention concerns a method for treatment of Paget's disease of bone, hype ⁇ arathyroidism, malignant neoplasms, parodontal diseases, prosthetic and/or implant related bone loss, tumours, AIDS and disorders related thereto, Alzheimer's disease, angiogenesis, atherosclerosis, rheumatoid arthritis, diabetic retinopathy, psoriasis or diabetes, wherein said method comprises administering to a human or animal patient a therapeutically effective amount of an imidazopyridine carbonitrile compound according to any one of the previously outlined embodiments.
  • the typical daily dose of the active ingredient varies within a wide range and will depend on various factors such as e.g. the individual requirement of each patient, the route of administration and the disease.
  • oral and parenteral doses will usually be in the range of 1 to 1000 mg, preferably 1-300 mg, per day of the active ingredient.
  • the present invention relates to pharmaceutical compositions containing at least one compound according to the invention, or a therapeutically acceptable salt thereof, as active ingredient.
  • the pharmaceutically acceptable salts include acid addition salts. Acids that form therapeutically acceptable salts are e.g.
  • hydrohalogen acids such as hydrochloric acid, sulphuric acid, phosphoric acid, nitric acid, aliphatic, alicyclic, aromatic or heterocyclic carboxyl or sufphonic acids, such as formic acid, acetic acid, propionic acid, succinic acid, glycolic acid, lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid, maleic acid, hydroxymaleic acid, pyruvic acid, p -hydroxybensoic acid, embonic acid, methanesulphonic acid, ethanesulphonic acid, hydroxyethanesulphonic acid, halogenbenquentphonic acid, toluenesulphonic acid and naphtalenesulphonic acid.
  • hydrohalogen acids such as hydrochloric acid, sulphuric acid, phosphoric acid, nitric acid, aliphatic, alicyclic, aromatic or heterocyclic carboxyl or sufphonic acids, such as formic acid, acetic acid,
  • an imidazopyridine carbonitrile compound for use as a pharmaceutical.
  • it may be used in pharmaceutical compositions for oral, intravenous, topical, intraperitoneal or subcutaneous administration, in association with one or more pharmaceutically acceptable carriers, diluents or adjuvants that are well known in the art.
  • composition of the invention may be administered topically, in the form of solutions, suspensions or systemically, e.g. by oral administration in the form of tablets, capsules, syrups, powders or granules or by parenteral administration in the form of solutions or suspensions, or by subcutaneous administration or by rectal administration in the form of suppositories or transdermally.
  • Membrane vesicles were prepared from egg-laying hens after 14 days of calcium-deprived diet, as previously described (Mattsson, J.P., Lorentzon, P., Wallmark, B., and Keeling, D.J., Biochim. Biophys. Acta., 1146(1), 106-12 (1993)), with some modifications.
  • the medullary bone scraped from the long bones was resuspended in isolation buffer (1 ml/g medullary bone) containing 5 mM Hepes/Tris, pH 7.4, 250 raM sucrose and 1 mM EGTA, minced using a pair of scissors, diluted 1 :10 (w/v) in isolation buffer and homogenised in a polytron homogeniser. The homogenate was filtered through a 250 ⁇ m nylon mesh. Membrane vesicles were then obtained by differential centrifugation (2000 x g for 10 min, 10,000 x g for 20 min and 40,000 x g for 1 h). The final pellet was resuspended in isolation buffer (0.4 ml/g medullary bone) by 20 passes using a teflon/glass homogenizer, snap frozen in MeOH/dry ice and then stored at -70°C.
  • Bovine brain Fresh bovine brains were obtained from a local slaughter house. Membrane vesicles were prepared from whole brain exactly as described for the medullary bone membrane vesicles.
  • Proton transport in membrane vesicles was measured in a 96-well plate reader using the weak base acridine orange (Mattsson, J.P., Lorentzon, P., Wallmark, B., and Keeling, D.J., Biochim. Biophys. Acta., 1146(1), 106-12 (1993)).
  • Test substances dissolved in DMSO or DMSO (control) were added to the wells of a 96-well plate, followed by the addition of 220 ⁇ l acridine-orange buffer (final concentrations: 5 mM Hepes/Tris, pH 7.4, 125 mM KC1, 3 mM MgSO4, 0.25 mM DTT, 1 ⁇ M valinomycin and 5 ⁇ M acridine orange) and membrane vesicles (10-50 ⁇ g protein).
  • 220 ⁇ l acridine-orange buffer final concentrations: 5 mM Hepes/Tris, pH 7.4, 125 mM KC1, 3 mM MgSO4, 0.25 mM DTT, 1 ⁇ M valinomycin and 5 ⁇ M acridine orange
  • membrane vesicles 10-50 ⁇ g protein.
  • mice were injected with a 45 Ca -solution (0.25 ml 120 ⁇ Ci/ml, s.c), day 2 and 1 before partus.
  • the new-born mice were 5 to 8 days old, they were killed by decapitation and the calvaria were dissected out and cut into four equally sized pieces.
  • the pieces were placed in petri dishes containing incubation medium (1 mM L-glutamine, 100 U/ml penicillin, 100 ⁇ g/ml streptomycin, 1 mg/ml albumin and 1 ⁇ M indomethacin) with or without 10 nM PTH and preincubated in a CO2 incubator (5% CO2 in air) for 20-24 h at 37°C.
  • the calvaria pieces were then transferred to a 24-well plate containing fresh incubation medium. After 24 h, an aliquot (400 ⁇ l) of the incubation medium was analysed for the content of 45 Ca in a Microbeta (Wallac) scintillation counter (Control CPM).
  • the calvaria pieces were transferred to fresh incubation medium and incubated with or without test substance and after another 24 h incubation, an aliquot (400 ⁇ l) of the incubation medium was analysed for the content of 4s Ca (Compound CPM).
  • the reso ⁇ tion ratio between the control period and the compound period was calculated and dose-response curves constructed using the 4-parameter logistic equation.
  • Protein determination Protein was determined according to Bradford (Bradford, M.M., Anal. Biochem., 72, 248-54 (1976)) using Bio Rad's protein assay kit and ⁇ -globulin as a standard.

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Abstract

L'invention concerne un inhibiteur sélectif de l'activité d'ostéoclastes de mammifères, leurs procédés de préparation et des compositions pharmaceutiques les contenant, ainsi que des méthodes de traitement consistant à administrer ledit inhibiteur sélectif à un patient humain ou animal. On a constaté que ledit inhibiteur sélectif inhibe la H+-ATPase vacuolaire dans les ostéoclastes, et qu'il est donc efficace, au plan thérapeutique, contre les troubles physiologiques impliquant la résorption osseuse. Dans un mode de réalisation de l'invention, ledit inhibiteur comprend un composé imidazopyridine carbonitrile de formule générale I.
PCT/SE2000/001860 1999-10-06 2000-09-26 Nouveaux composes imidazopyridine carbonitrile WO2001025237A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
JP2001528181A JP2003511381A (ja) 1999-10-06 2000-09-26 新規なイミダゾピリジンカルボニトリル化合物
EP00970372A EP1222188A1 (fr) 1999-10-06 2000-09-26 Nouveaux composes imidazopyridine carbonitrile
CA002385251A CA2385251A1 (fr) 1999-10-06 2000-09-26 Nouveaux composes imidazopyridine carbonitrile
AU79764/00A AU7976400A (en) 1999-10-06 2000-09-26 Novel imidazopyridine carbonitrile compounds

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SE9903611A SE9903611D0 (sv) 1999-10-06 1999-10-06 Novel compounds III
SE9903611-3 1999-10-06

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JP (1) JP2003511381A (fr)
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Cited By (9)

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US10513493B2 (en) 2014-02-13 2019-12-24 Incyte Corporation Cyclopropylamines as LSD1 inhibitors
US10556908B2 (en) 2014-07-10 2020-02-11 Incyte Corporation Substituted imidazo[1,2-a]pyrazines as LSD1 inhibitors
US10640503B2 (en) 2014-07-10 2020-05-05 Incyte Corporation Imidazopyridines and imidazopyrazines as LSD1 inhibitors
US10676457B2 (en) 2014-02-13 2020-06-09 Incyte Corporation Cyclopropylamines as LSD1 inhibitors
US10717737B2 (en) 2014-02-13 2020-07-21 Incyte Corporation Cyclopropylamines as LSD1 inhibitors
US10723700B2 (en) 2015-08-12 2020-07-28 Incyte Corporation Salts of an LSD1 inhibitor
US10800779B2 (en) 2015-04-03 2020-10-13 Incyte Corporation Heterocyclic compounds as LSD1 inhibitors
US10968221B2 (en) 2014-07-10 2021-04-06 Incyte Corporation Substituted [1,2,4]triazolo[1,5-a]pyrazines as LSD1 inhibitors
US10968200B2 (en) 2018-08-31 2021-04-06 Incyte Corporation Salts of an LSD1 inhibitor and processes for preparing the same

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US4751227A (en) * 1985-03-26 1988-06-14 Eisai Co., Ltd. 3-cyano-5-(6-imidazo[1,2-a]pyridyl)pyridin-2-ols useful as cardiotonics
WO1997014681A1 (fr) * 1995-10-16 1997-04-24 Fujisawa Pharmaceutical Co., Ltd. Composes heterocycliques tels que des h+-atpases
WO1998001443A1 (fr) * 1996-07-09 1998-01-15 Smithkline Beecham S.P.A. Derives d'indole pour le traitement de l'osteoporose

Patent Citations (4)

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Publication number Priority date Publication date Assignee Title
US4751227A (en) * 1985-03-26 1988-06-14 Eisai Co., Ltd. 3-cyano-5-(6-imidazo[1,2-a]pyridyl)pyridin-2-ols useful as cardiotonics
FR2581646A1 (fr) * 1985-05-07 1986-11-14 Synthelabo Derives d'imidazopyridine, leur preparation et leur application en therapeutique
WO1997014681A1 (fr) * 1995-10-16 1997-04-24 Fujisawa Pharmaceutical Co., Ltd. Composes heterocycliques tels que des h+-atpases
WO1998001443A1 (fr) * 1996-07-09 1998-01-15 Smithkline Beecham S.P.A. Derives d'indole pour le traitement de l'osteoporose

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JP2003511381A (ja) 2003-03-25
AU7976400A (en) 2001-05-10

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