[go: up one dir, main page]

WO2024236055A1 - Dérivés de pyrazolidine-3,5-dione utilisés comme traceurs tep pour l'imagerie du récepteur p2y12 - Google Patents

Dérivés de pyrazolidine-3,5-dione utilisés comme traceurs tep pour l'imagerie du récepteur p2y12 Download PDF

Info

Publication number
WO2024236055A1
WO2024236055A1 PCT/EP2024/063411 EP2024063411W WO2024236055A1 WO 2024236055 A1 WO2024236055 A1 WO 2024236055A1 EP 2024063411 W EP2024063411 W EP 2024063411W WO 2024236055 A1 WO2024236055 A1 WO 2024236055A1
Authority
WO
WIPO (PCT)
Prior art keywords
pyrazolidine
pharmaceutically acceptable
acceptable salt
dione compound
compound
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.)
Pending
Application number
PCT/EP2024/063411
Other languages
English (en)
Inventor
Johanna STÉEN
Berend VAN DER WILDT
Albert D. WINDHORST
Iwan J. P. DE ESCH
Barbara ZARZYCKA
Danielle J. Vugts
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.)
Vrije Universiteit Amsterdam
Amsterdam UMC Foundation
Original Assignee
Vrije Universiteit Amsterdam
Amsterdam UMC Foundation
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 Vrije Universiteit Amsterdam, Amsterdam UMC Foundation filed Critical Vrije Universiteit Amsterdam
Publication of WO2024236055A1 publication Critical patent/WO2024236055A1/fr
Anticipated expiration legal-status Critical
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/28—Two oxygen or sulfur atoms
    • C07D231/30—Two oxygen or sulfur atoms attached in positions 3 and 5
    • C07D231/32—Oxygen atoms

Definitions

  • TITLE PYRAZOLIDINE-3, 5-DIONE DERIVATIVES AS PET TRACERS FOR IMAGING THE P2Y12 RECEPTOR
  • the present invention relates to pyrazolidine-3, 5-dione compounds or pharmaceutically acceptable salts thereof for use as radioactive tracer compounds in monitoring neuroinflammation in neurodegenerative and neurological diseases such as, but not limited to, Alzheimer’s disease, Parkinson’s disease, Multiple sclerosis, in an individual by positron emission tomography (PET) or single photon emission computed tomography (SPECT).
  • PET positron emission tomography
  • SPECT single photon emission computed tomography
  • the present invention also relates to methods for making pyrazolidine-3, 5-dione compounds or pharmaceutically acceptable salts thereof for use as radioactive tracer compounds in monitoring neuroinflammation in neurodegenerative and neurological diseases such as, but not limited to, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis in an individual.
  • the present invention further relates to a composition for use as radioactive tracer compounds in monitoring neuroinflammation in neurodegenerative and neurological diseases such as, but not limited to, Alzheimer’s disease, Parkinson’s disease, Multiple sclerosis in an individual.
  • the P2Y12 receptor plays a key role in neuroinflammation, which is a hallmark of several neurological and neurodegenerative diseases.
  • the P2Yn purinergic receptor 12 (P2YnR) is a G-protein coupled receptor expressed on microglia.
  • the P2Y12R is frequently said to be a marker of so-called antiinflammatory microglia. Thus, it can be a target for a PET tracer to image microglia that are in the antiinflammatory status.
  • PET selective positron emission tomography
  • the P2Y12R is a highlighted target for imaging the neuroprotective, anti-inflammatory, state of microglia during neuroinflammation due to its up-regulation on this state and down-regulation on the pro- inflammatory microglia state.
  • Parkinson’s disease is a progressive disorder of degeneration of nerve cells in the substantia nigra, which controls movement. These nerve cells die or become impaired, losing the ability to produce an important chemical called dopamine. Parkinson's is the second-most common neurodegenerative disease after Alzheimer's disease. More than 10 million people worldwide are living with PD, out of which approx, one million patients are only from the USA. These 1 million patients ae expected to be 1.2 million by 2030.
  • Alzheimer’s disease is a brain disorder that slowly destroys memory and thinking skills, and eventually, the ability to carry out the simplest tasks. In most people with Alzheimer’s, symptoms first appear later in life.
  • Alzheimer’s is currently ranked as the seventh leading cause of death in the United States and is the most common cause of dementia among older adults.
  • Multiple sclerosis is a neuroinflammatory disease which often presents itself in subjects of relatively young age (30-45 years old) and as such a major societal impact.
  • the molecular status of the neuroinflammation can only be assessed with PET or SPECT. Magnetic Resonance Imaging can detect the presence of neuroinflammation, but not the molecular status of the neuroinflammation.
  • a tracer for the P2Y12R will provide detailed information regarding microglia in the antiinflammatory status. This will complement tracers targeting the translocator protein 18kDa (TSPO) that allows for imaging the total pool of activated microglia and the P2X? receptor, which allows for imaging the microglia in the pro-inflammatory status.
  • TSPO translocator protein 18kDa
  • the dynamics of microglia activation during neuroinflammation can be imaged with PET or SPECT in several neurodegenerative and neurological diseases, such as, but not limited to, Alzheimer’s disease, Parkinson’s disease, and Multiple sclerosis.
  • PET tracers targeting the P2Y 12R have been made to obtain PET tracers targeting the P2Y 12R.
  • P2Y 12R antagonists used as anti -thrombotic agents are not designed to target the receptor in the brain.
  • all the previously reported compounds are either substrates for efflux transporter proteins in the bloodbrain barrier or have non-favorable physicochemical properties for brain uptake.
  • a successful P2YnR PET or SPECT tracer has some advantages. Firstly, the dynamical changes of microglia and P2Y12R- mediated actions can be studied in the living brain, which will provide detailed information regarding its molecular mechanisms and fill the current knowledge gaps.
  • P2Y12R PET or SPECT will facilitate development of potential drugs that can slow down or reverse disease progression, by accurate assessment of drug effects in the brain.
  • Main objective of the present invention is to provide pyrazolidine-3, 5-dione compounds or pharmaceutically acceptable salts thereof.
  • Another objective of the present invention is to provide pyrazolidine-3, 5-dione compounds or pharmaceutically acceptable salts thereof for monitoring a disease therapy related to neurodegenerative and neurological diseases, such as, but not limited to, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis in an individual.
  • a disease therapy related to neurodegenerative and neurological diseases such as, but not limited to, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis in an individual.
  • Yet another objective of the present invention is to provide a composition for monitoring neuroinflammation in neurodegenerative and neurological diseases, such as, but not limited to, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis in an individual.
  • Still another objective of the present invention is to provide a method for making pyrazolidine-3, 5- dione compounds or pharmaceutically acceptable salts thereof.
  • Yet another objective of the present invention is to provide the pyrazolidine-3, 5-dione compounds or pharmaceutically acceptable salts thereof or composition for use in predicting and/or monitoring and/or detecting and/or quantifying the P2YnR or monitoring the dynamic changes of microglia during neuroinflammation.
  • Still another objective of the present invention is to provide the radioactive tracer compounds for monitoring a disease therapy in an individual by imaging the neuroprotective state of microglia during or prior to its inflammatory state for monitoring the neurodegenerative and neurological diseases.
  • Yet another objective of the present invention is to provide radioactive tracer compounds for use in in vivo monitoring the diseases associated with the P2Y12R.
  • Still another objective of the present invention is to provide pyrazolidine-3, 5-dione compounds or pharmaceutically acceptable salts thereof, radioactive tracer compounds for use as imaging agents to image the P2Y 12R in vivo using positron emission tomography (PET) or single photon emission computed tomography (SPECT).
  • PET positron emission tomography
  • SPECT single photon emission computed tomography
  • Yet another objective of the present invention is to provide pyrazolidine-3, 5-dione compounds or pharmaceutically acceptable salts thereof for method of treating a disease such as, but not limited to, alzheimer’s disease, parkinson’s disease and multiple sclerosis.
  • Main aspect of the present invention provides a pyrazolidine-3, 5 -dione compound represented by Formula (I):
  • X is CH 2 , O, S, NH, C(O)NH and NHC(O);
  • Another aspect of the present invention provides a pyrazolidine-3, 5-dione compound represented by Formula (IA) or pharmaceutically acceptable salt thereof, wherein:
  • X is CH 2 , O, S, NH, C(O)NH and NHC(O);
  • Yet another aspect of the present invention provides a process for making pyrazolidine-3, 5-dione compounds of formula (I) or compounds of formula IA or pharmaceutically acceptable salts thereof, comprising reacting the pyrazolidine-3, 5-dione compound of formula (I), with 18 F, 19 F, 123 I, 124 I, 127 I, 131 I.
  • Yet another aspect of the present invention provides pyrazolidine-3, 5-dione compounds or pharmaceutically acceptable salts thereof in monitoring a disease therapy related to neuroinflammation in neurodegenerative and neurological diseases such as, but not limited to, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis in an individual.
  • Still another aspect of the present invention provides a composition for monitoring a disease therapy for neuroinflammation in neurodegenerative and neurological diseases such as, but not limited to, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis in an individual.
  • a disease therapy for neuroinflammation in neurodegenerative and neurological diseases such as, but not limited to, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis in an individual.
  • Yet another aspect of the present invention provides the pyrazolidine-3, 5-dione compounds or pharmaceutically acceptable salts thereof or composition for use in predicting and/or monitoring and/or detecting and/or quantifying the P2Y 12R or monitoring the dynamic changes in microglia or macrophages.
  • Still another aspect of the present invention provides the radioactive tracer compounds in monitoring a disease therapy in an individual by imaging the neuroprotective state of microglia during or prior to its inflammatory state for monitoring the neurodegenerative and neurological diseases.
  • Yet another aspect of the present invention provides radioactive tracer compounds for use in in vivo monitoring the diseases associated with the P2Y12R.
  • Still another aspect of the present invention provides pyrazolidine-3, 5-dione compounds or pharmaceutically acceptable salts thereof, radioactive tracer compounds for use as imaging agents to image the P2Y 12R in vivo using positron emission tomography (PET) or single photon emission computed tomography (SPECT)
  • PET positron emission tomography
  • SPECT single photon emission computed tomography
  • Still another aspect of the present invention provides pyrazolidine-3, 5-dione compounds or pharmaceutically acceptable salt sthereof for method of treating a disease selected from Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis.
  • a disease selected from Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis.
  • Figure 1 Illustrates compound overview including structures of co-crystallized ligand AZDI 283 and pyrazolidine-3, 5 -diones derivatives 1-3, along with the predicted binding modes compounds 2 and 3 in the AZD1283 binding sites of the P2Y12R.
  • Figure 2 Illustrates synthesis of pyrazolidine-3, 5 -di ones 2 and 3.
  • FIG. 3 Illustrates the Time-Activity Curves (TACs) of [ 18 F]JOSE198 (i.e., compound 18 F9) in brain post-administration of the tracer compound.
  • TACs Time-Activity Curves
  • pharmaceutically acceptable is used to specify that an object (for example a salt, dosage form, excipient) is suitable for use in patients.
  • geometric isomers refers to two or more coordination compounds which contain the same number and types of atoms, and bonds, but which have different spatial arrangements of the atoms.
  • microglia includes the resident immune cells of the central nervous system (CNS), which play an important role in CNS homeostasis during development, adulthood, and ageing.
  • CNS central nervous system
  • Macrophages includes a type of white blood cells that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells.
  • Radioactive tracer compounds are chemical compounds in which one or more atoms have been replaced by a radionuclide.
  • the term "therapy” is intended to have its normal meaning of dealing with a disease in order to entirely or partially relieve one, some or all of its symptoms, or to correct or compensate for the underlying pathology.
  • the term “therapy” also includes “prophylaxis” unless there are specific indications to the contrary.
  • the terms “therapeutic” and “therapeutically” should be interpreted in a corresponding manner.
  • treatment is used synonymously with “therapy”.
  • treat can be regarded as “applying therapy” where “therapy” is as defined herein.
  • A is selected from
  • Ri is selected from a group comprising of H, OH, represents geometric isomers wherein cis or trans is not defined;
  • X is CH 2 , O, S, NH, C(O)NH and NHC(O);
  • R 2 cannot be H.
  • Another embodiment of the present invention discloses a pyrazolidine-3,5-dione compound represented by Formula (IA) or pharmaceutically acceptable salt thereof, wherein:
  • X is CH 2 , O, S, NH, C(O)NH and NHC(O);
  • R2 is selected from a group comprising of H, 18 F, 19 F 123 I, 124 I, 127 I, 131 I; wherein one of Ri and R2 represents a group having 18 F, 19 F, 123 I, 124 I, 127 I, 131 I moiety.
  • Yet another embodiment of the present invention discloses the pyrazolidine-3, 5-dione compounds or pharmaceutically acceptable salts thereof, wherein Ri is selected from a group comprising of ; R2 is selected from a group comprising of H,
  • R2 cannot be H.
  • Still another embodiment of the present invention discloses the pyrazolidine-3, 5-dione compounds or pharmaceutically acceptable salts thereof, wherein Ri and R2 are H.
  • Yet another embodiment of the present invention discloses the pyrazolidine-3, 5-dione compounds or pharmaceutically acceptable salts thereof, wherein the compounds are represented by the following
  • Still another embodiment of the present invention discloses the pyrazolidine-3, 5-dione compounds
  • Yet another embodiment of the present invention discloses a process for making a pyrazolidine-3, 5- dione compound of formula (I) or pharmaceutically acceptable salt thereof, comprising reacting the pyrazolidine-3, 5-dione compound of formula (I), with 18 F, 19 F, 123 I, 124 I, 127 I, 131 I.
  • Still another embodiment of the present invention discloses a process for making a pyrazolidine- 3, 5-dione compound of formula (I) or pharmaceutically acceptable salt thereof, wherein Ri is selected from group having 18 F or 19 F moiety; R2 is H, comprising reaction of pyrazolidine-3, 5-dione compound of formula (I), with 18 F- labeled or 19 F- labeled compound.
  • Ri is selected from group having 18 F or 19 F moiety
  • R2 is H
  • Still another embodiment of the present invention discloses the process, wherein 18 F- labeled compound is [ 18 F]l-bromo-3-(fluoro)propane and 19 F- labeled compound is [ 19 F]l-bromo-3- (fluoro)propane.
  • Still another embodiment of the present invention discloses a composition
  • a composition comprising a pyrazolidine-3, 5-dione compound or pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable excipient.
  • Yet another embodiment of the present invention discloses the pyrazolidine-3, 5-dione compound or pharmaceutically acceptable salt thereof or composition, for use in predicting and/or monitoring and/or detecting and/or quantifying the P2Y12R or monitoring the dynamic changes in microglia or macrophages in vivo.
  • Still another embodiment of the present invention discloses the pyrazolidine-3, 5-dione compound or pharmaceutically acceptable salt thereof, or composition, for use as radioactive tracer compounds in in vivo monitoring a disease therapy in an individual by imaging the neuroprotective state of microglia during or prior to its inflammatory state for monitoring the neurodegenerative and neurological diseases.
  • Yet another embodiment of the present invention discloses the pyrazolidine-3, 5-dione compound or pharmaceutically acceptable salt thereof, or composition, for use in in vivo monitoring the diseases associated with the P2Y12R (P2YnR such as, but not limited to, Alzheimer’s disease, Parkinson’s disease and multiple sclerosis.
  • P2YnR P2Y12R
  • Still another embodiment of the present invention discloses the pyrazolidine-3, 5-dione compounds or pharmaceutically acceptable salts thereof, or composition, for use as imaging agents to image the P2YnR in vivo using positron emission tomography (PET) or singel photon emission computed tomography (SPECT) in predicting and/or monitoring and/or detecting and/or quantifying the P2YnR or monitoring the dynamic changes in microglia.
  • PET positron emission tomography
  • SPECT singel photon emission computed tomography
  • Yet another embodiment of the present invention discloses a method for detection and/or prediction and/or monitor and/or quantification of the P2YnR or monitor the dynamic changes in microglia and macrophages, comprising contacting P2Y12R with an amount of compound or pharmaceutically acceptable salt thereof which is sufficient to be detected by Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT) by forming at least one PET or SPECT image and determining the actual state of P2Y 12R by observing the image.
  • PET Positron Emission Tomography
  • SPECT Single Photon Emission Computed Tomography
  • Still another embodiment of the present invention discloses the pyrazolidine-3, 5-dione compound or pharmaceutically acceptable salt thereof, or composition, for use in method of treating a disease selected from Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis.
  • PET tracer compounds have been designed and synthesized based on molecular docking. To evaluate their affinity toward the receptor, competitive binding studies were carried out against a 3 H- labeled P2Y12R antagonist on membrane preparations prepared from HEK-293 cells or CHO cells transfected with the human P2Y12R. The following compounds showed high affinity toward the receptor with values below 10 nM such as 1.16 nM and 1.43 nM. [062] Binding affinities were also evaluated on membrane preparations prepared from HEK-293 transfected with the rat P2Y 12R (rP2Y12R). The following compounds showed high affinity.
  • N-Bromo succinimide (1.43 g, 8.01 mmol, 1.50 eq) was added. The mixture was stirred for 16 h at room temperature. After solvent evaporation in vacuo, the residue was diluted with DCM (50 mL) and washed with sat. NaHCCE (3 x 50 mL) and brine (50 mL) Flash column chromatography (EA/hexane 1:9) afforded to title compound as a white crystal (260 mg, 18%).
  • Ethyl malonyl chloride (1.25g, 8.25mmol, 1.00 eq) was added dropwise at -10 °C to a solution of 4- fluorophenylhydrazine hydrochloride (1.35g, 8.25mmol, 1.00 eq) and TEA (1.26g, 12.5 mmol, 1.50 eq) in THF (25ml). The mixture was warmed to room temperature and stirred for 16 h. The reaction mixture was portioned between DCM (25ml) and H2O (25ml). The organic layer was extracted, washed with brine (25ml) and concentrated in vacuo. The obtained residue was further treated with ethanolic NaOH (15ml, 15.0 mmol, IM).
  • the formed [ 18 F]triflyl fluoride was distilled over a drying column (P2O5) into a vial containing K222/KHCO3 (40/40 pmol) in dry MeCN (900 pL) to trap it as dried [ 18 F]F .
  • the distillation was finished after approximately 5-10 min.
  • the collected fraction was diluted with water (20 mL), and the product ([ 18 F] 13) was trapped on a tC18 cartridge (Sep-Pak tC18 plus short cartridge, Waters).
  • the cartridge was washed with water (10 mL) and [ 18 F]13 eluted with diethyl ether (2 mL) by also passing it through a Sep-Pak dry (long) to remove residual water.
  • the diethyl ether was removed by a stream of He flow (35 mL/min) at 35 °C for 5-10 min.
  • the product was obtained in high radiochemical purity 95-99%.
  • Figure 1 illustrates the compound overview including structures of co-crystallized ligand AZDI 283 and pyrazolidine-3, 5-diones derivatives 1-3, along with the predicted binding modes compounds 2 and 3 in the AZD1283 binding sites of the P2Y12R.
  • fluorine is introduced in a position that is placed in a hydrophobic environment.
  • the fluoropropyl moiety of 2 is placed in the narrow hydrophobic region created by residues Vall02, Phel06, Tyrl09, Metl52 and Leul55 whereas the fluorine in the 4- position of the phenyl substituent of 3 is positioned in a larger sub pocket formed by the residues Phe252, Arg256, Tyr259 and Leu276.
  • the CNS PET MPO scores for both compounds were more than 3, indicating a high probability for successful brain tracer.
  • the high-affinity PET tracer candidates for imaging the P2Y12R were developed based on a pyrazolidine-3, 5-dione scaffold.
  • the P2Y12RPET tracer would allow for imaging of microglia dynamics, an important step in the research regarding neuroinflammatory diseases.
  • the results can be seen in Figure 3.
  • Said Figure shows the Time-Activity Curves (TACs) of [ 18 F]JOSE198 (i.e., compound 18 F9) in brain for each rat up to 1 h post-administration of the tracer compound.
  • TACs Time-Activity Curves
  • n-BuLi n-butyllithium
  • NBS A-bromosuccinimide

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un composé pyrazolidine-3,5-dione représenté par la formule (I) ou un sel pharmaceutiquement acceptable de celui-ci, destiné à être utilisé comme composés traceurs radioactifs dans la surveillance d'un traitement d'une maladie chez un individu par imagerie de l'état neuroprotecteur de la microglie pendant ou avant son état inflammatoire pour surveiller les maladies neurodégénératives et neurologiques.
PCT/EP2024/063411 2023-05-15 2024-05-15 Dérivés de pyrazolidine-3,5-dione utilisés comme traceurs tep pour l'imagerie du récepteur p2y12 Pending WO2024236055A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP23173438 2023-05-15
EP23173438.5 2023-05-15

Publications (1)

Publication Number Publication Date
WO2024236055A1 true WO2024236055A1 (fr) 2024-11-21

Family

ID=86383171

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2024/063411 Pending WO2024236055A1 (fr) 2023-05-15 2024-05-15 Dérivés de pyrazolidine-3,5-dione utilisés comme traceurs tep pour l'imagerie du récepteur p2y12

Country Status (1)

Country Link
WO (1) WO2024236055A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002102359A2 (fr) * 2001-06-18 2002-12-27 Applied Research Systems Ars Holding N.V. Derives d'alkylidene pyrazolidinedione
WO2005000281A2 (fr) * 2003-06-24 2005-01-06 Actelion Pharmaceuticals Ltd. Derives de pyrazolidinedione
WO2015140572A1 (fr) * 2014-03-20 2015-09-24 Isis Innovation Limited Procédé de fluoration

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002102359A2 (fr) * 2001-06-18 2002-12-27 Applied Research Systems Ars Holding N.V. Derives d'alkylidene pyrazolidinedione
WO2005000281A2 (fr) * 2003-06-24 2005-01-06 Actelion Pharmaceuticals Ltd. Derives de pyrazolidinedione
WO2015140572A1 (fr) * 2014-03-20 2015-09-24 Isis Innovation Limited Procédé de fluoration

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
JUN MAEDA ET AL., DISTINCT MICROGLIAL RESPONSE AGAINST ALZHEIMER'S AMYLOID AND TAU PATHOLOGIES CHARACTERIZED BY P2Y12 RECEPTOR
MA BEN B ET AL: "Strategies for targeting the P2Y12 receptor in the central nervous system", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, ELSEVIER, AMSTERDAM NL, vol. 71, 28 May 2022 (2022-05-28), XP087099683, ISSN: 0960-894X, [retrieved on 20220528], DOI: 10.1016/J.BMCL.2022.128837 *

Similar Documents

Publication Publication Date Title
JP7631235B2 (ja) 多発性硬化症のようなｃｎｓ障害を治療するためのｇｐｒ１７モジュレーターとしてのｎ‐（フェニル）‐インドール‐３‐スルホンアミド誘導体及び関連化合物
RU2627694C2 (ru) Производные хинолина, визуализирующий белок тау
JP5272110B2 (ja) 新規アミロイド親和性化合物
EP2321279A1 (fr) Daa-pyridine comme ligand des récepteurs périphériques des benzodiazépines pour l'imagerie de diagnostic et le traitement pharmaceutique
JP2017508782A (ja) 炭素環式スルホンＲＯＲγ調節因子
US10300155B2 (en) Alpha-synuclein ligands
JP7456948B2 (ja) 放射性標識カンナビノイド受容体２リガンド
CN104470898A (zh) 环烷基甲酸类衍生物、其制备方法及其在医药上的应用
TW200901998A (en) Novel 2-heteroaryl substituted benzothiophenes and benzofuranes
Fujinaga et al. Synthesis and evaluation of 6-[1-(2-[18F] fluoro-3-pyridyl)-5-methyl-1H-1, 2, 3-triazol-4-yl] quinoline for positron emission tomography imaging of the metabotropic glutamate receptor type 1 in brain
CN117940435A (zh) 用于诊断tdp-43蛋白质病的新化合物
JP5778164B2 (ja) 放射標識ｐｄｅ１０リガンド
Kaide et al. 18F-labeled benzimidazopyridine derivatives for PET imaging of tau pathology in Alzheimer’s disease
US20160009644A1 (en) Potent and selective inhibitors of monoamine transporters; method of making; and use thereof
JP2025534373A (ja) Ｔｄｐ－４３プロテイノパチーを診断するための新規化合物
WO2024236055A1 (fr) Dérivés de pyrazolidine-3,5-dione utilisés comme traceurs tep pour l'imagerie du récepteur p2y12
WO2024001967A1 (fr) Composé d'imidazonaphtyridine ayant une affinité avec la protéine tau, son procédé de préparation et son utilisation
Fabio et al. Synthesis and evaluation of potent and selective human V1a receptor antagonists as potential ligands for PET or SPECT imaging
Kumata et al. Synthesis and evaluation of 4-(2-fluoro-4-[11C] methoxyphenyl)-5-((2-methylpyridin-4-yl) methoxy) picolinamide for PET imaging of the metabotropic glutamate receptor 2 in the rat brain
WO2012176587A1 (fr) Nouveau composé ayant une affinité pour l'amyloïde
WO2024123700A1 (fr) Inhibiteurs d'histone désacétylase
Hassan et al. Fluorinated CRA13 analogues: Synthesis, in vitro evaluation, radiosynthesis, in silico and in vivo PET study
CN106715444A (zh) 新型色酮肟衍生物以及其作为代谢型谷氨酸受体的别构调节剂的用途
US20060171881A1 (en) Compounds with high monoamine transporter affinity
US20110280804A1 (en) Highly selective sigma receptor radioligands

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 24725222

Country of ref document: EP

Kind code of ref document: A1