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WO2025177150A1 - Composé utilisé en tant qu'inhibiteur de parp1 et composition pharmaceutique le comprenant - Google Patents

Composé utilisé en tant qu'inhibiteur de parp1 et composition pharmaceutique le comprenant

Info

Publication number
WO2025177150A1
WO2025177150A1 PCT/IB2025/051745 IB2025051745W WO2025177150A1 WO 2025177150 A1 WO2025177150 A1 WO 2025177150A1 IB 2025051745 W IB2025051745 W IB 2025051745W WO 2025177150 A1 WO2025177150 A1 WO 2025177150A1
Authority
WO
WIPO (PCT)
Prior art keywords
methyl
mmol
fluoro
dihydrooxazin
pyridin
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/IB2025/051745
Other languages
English (en)
Inventor
Moo Sung Ko
Il Hyang Kim
Younghue HAN
Jaeyoung Lee
Dahae Lee
Mijin Yoon
Uji KIM
Keesoo NAM
Junho Cho
Hyunmo YANG
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.)
Chong Kun Dang Corp
Original Assignee
Chong Kun Dang Corp
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Filing date
Publication date
Application filed by Chong Kun Dang Corp filed Critical Chong Kun Dang Corp
Publication of WO2025177150A1 publication Critical patent/WO2025177150A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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Classifications

    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5355—Non-condensed oxazines and containing further heterocyclic rings
    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/538—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with carbocyclic ring 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5386—1,4-Oxazines, e.g. morpholine spiro-condensed or forming part of bridged ring 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
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/5415—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
    • 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
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems

Definitions

  • the present invention relates to a compound, stereoisomers thereof, pharmaceutically acceptable salts thereof as a PARP1 inhibitor and a pharmaceutical composition including the same, and a method for preventing or treating PARP1 activity- associated diseases using the same and a use thereof.
  • PARP poly(ADP-ribose)polymerase
  • PARP1 and PARP2 are the most extensively studied PARPs for their roles in DNA damage repair.
  • PARP1 is activated by DNA damage break and functions to catalyze the addition of poly(ADP-ribose) (PAR) chains to a target protein.
  • PARylation This post-translational modification, known as PARylation, mediates recruitment of additional DNA repair factors into DNA lesions.
  • PARP self-PARylation triggers release of bound PARP from DNA, thus allowing access to other DNA repair proteins to complete the repair.
  • binding of PARP to an injured site, catalytic activity thereof, and eventual release thereof from DNA are all important steps in which cancer cells respond to DNA damage caused by chemotherapy and radiation therapy (Bai P. Biology of poly(ADP-ribose) polymerases: the factotums of cell maintenance. Mol Cell 2015;58:947-58.).
  • Inhibition of the PARP family enzyme was utilized as a strategy to selectively kill cancer cells by inactivating complementary DNA repair pathways.
  • a number of preclinical and clinical studies have demonstrated that tumor cells, including deleterious alterations of BRCA1 or BRCA2, the major tumor suppressor proteins involved in double-strand DNA break (DSB) repair by homologous recombination (HR), are selectively sensitive to small molecule inhibitors of DNA repair enzymes of the PARP family. These tumors have a defective homologous recombination repair (HRR) pathway and rely on PARP enzyme function for survival.
  • HRR homologous recombination repair
  • Patent Document 0001 International Patent Publication No. WO 2021/013735
  • Patent Document 0002 International Patent Publication No. WO 2021/260092
  • Non-Patent Document 0001 J. Med. Chem. 2021, 64, 19, 14498-14512
  • the present invention may provide a compound represented by a following formula
  • M is CR X , N, NR y , O, or S,
  • Ri and R2 are each independently H, halogen, OH, CN, C1-C5 alkyl, C1-C5 haloalkyl, C2-C5 alkenyl, C2-C5 alkynyl, or O-(C1-C5 alkyl),
  • M is CR X , N, O or S
  • X, Y and Z are each independently N or CR Z , each of R x and R z is independently H or halogen,
  • RA and RB are each independently H or C1-C5 alkyl, or RA and RB may be bonded to each other to form three- to seven-membered cycloalkyl,
  • Ri and R2 are each independently H, halogen, C1-C5 alkyl, C1-C5 haloalkyl, or O- (C1-C5 alkyl),
  • A is C6-C12 arylene or five- to 12-membered heteroarylene including one to three heteroatoms independently selected from the group consisting of N, O and S, and halogen may be F.
  • M is CR X , N, O or S
  • X, Y and Z are each independently N or CR Z , each of R x and R z is independently H or halogen,
  • RA and RB are each independently H or C1-C3 alkyl, or RA and RB may be bonded to each other to form four- to six-membered cycloalkyl, is a single bond or a double bond, is absent or a single bond,
  • Ri and R2 are each independently H, halogen, C1-C3 alkyl, C1-C3 haloalkyl, or O- (C1-C3 alkyl),
  • A is phenylene or five- to six-membered heteroarylene including one to three Ns, and halogen may be F.
  • Cm-Cn (in which m and n are each independently an integer of 1 or more) may mean the number of carbons, for example, “C1-C5 alkyl” may represent alkyl having one to five carbon atoms.
  • alkyl may mean a linear or branched saturated hydrocarbon group.
  • alkyl may have one to five carbon atoms.
  • alkyl may have one to four carbon atoms.
  • alkyl may have one to three carbon atoms.
  • Examples of alkyl may include methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, isobutyl, n-pentyl, sec -pentyl, tert-pentyl, isopentyl, sec-isopentyl, neo-pentyl, and the like, but are not limited thereto.
  • cycloalkyl may mean a saturated hydrocarbon ring having three or more carbon atoms, which may include both monocyclic and polycyclic structures.
  • cycloalkyl may be a ring having three to 12, three to ten, three to eight, or three to seven carbon atoms.
  • cycloalkyl may include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclopentyl, bicyclohexyl, bicycloheptyl, bicyclooctyl, bicyclononyl, spiropentyl, spirohexyl, spiroheptyl, spirooctyl, spirononyl, and the like, but are not limited thereto.
  • heterocyclo alkyl may mean a cyclic functional group in which at least one or more carbon atoms constituting the above-defined cycloalkyl ring are substituted with a heteroatom.
  • the heteroatom may include nitrogen (N), oxygen (O), or sulfur (S).
  • the heteroatoms included in the ring of heterocycloalkyl may be one type or two or more types, one or one or more of one type of heteroatom may be included therein, and at least one or more of the two or more types of heteroatoms may be included therein, respectively.
  • heterocycloalkyl may be a three- to 12-membered ring.
  • heterocycloalkyl may include oxiranyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, morpholinyl, piperazinyl, thiomorpholinyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, and the like, but are not limited thereto.
  • aryl may mean a monocyclic or polycyclic aromatic hydrocarbon ring. As one example, in the present invention, aryl may have six to 20 carbon atoms. As one example, in the present invention, aryl may have six to 12 carbon atoms. Examples of aryl may include phenyl, biphenyl, naphthalenyl, and the like, but are not limited thereto.
  • heteroaryl may mean a monocyclic or polycyclic aromatic hydrocarbon ring including at least one or more heteroatoms such as nitrogen (N), oxygen (O), or sulfur (S).
  • heteroaryl may be a five- to 12- membered ring.
  • heteroaryl may be a five- to 12- membered ring having one to three heteroatoms.
  • heteroaryl may be a five- to eight-membered ring having one to three heteroatoms.
  • heteroaryl may be a five- or six-membered ring having one or two heteroatoms.
  • stereoisomer may include a diastereomer and an optical isomer, which may include a single enantiomer, a mixture of enantiomers including a racemate, a single diastereomer, and a mixture of diastereomers all.
  • optical isomer may include a single enantiomer, a mixture of enantiomers including a racemate, a single diastereomer, and a mixture of diastereomers all.
  • Such isomer may be separated by resolution according to conventional techniques, for example, column chromatography, HPLC, or the like.
  • the isomer may be stereospecifically synthesized by using a known array of optically pure starting materials and/or reagents.
  • the isomer may be an optical isomer.
  • “pharmaceutically acceptable salts” may mean salts conventionally used in a pharmaceutical field, and may include, for example, inorganic ion salts prepared from calcium, potassium, sodium, magnesium, and the like; inorganic acid salts prepared from hydrochloric acid, nitric acid, phosphoric acid, bromic acid, iodic acid, perchloric acid, sulfuric acid, hydroiodic acid, etc.; organic acid salts prepared from acetic acid, trifluoroacetic acid, citric acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, mandelic acid, propionic acid, lactic acid, glycolic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbric acid, carbonic acid, vanillic acid, etc.; sulfonic acid salts prepared from methanesulfonic acid, ethan
  • the compound represented by formula 1 of the present invention may be the same as the compound list in this specification, but also include a pharmaceutically acceptable isotopic-labeled compound in which at least one or more atoms are replaced with an atom having the same atomic number but having an atomic mass or mass number different from the atomic mass or mass number prevailing in nature.
  • isotopes which may be included in the compound of the present invention may include: isotope of hydrogen, 2 H, 3 H; isotope of carbon, n C, 13 C, 14 C; isotope of chlorine, 36 Cl;isotope of fluorine, 18 F; isotope of iodine, 123 I, 125 I; isotope of nitrogen, 13 N, 15 N; isotope of oxygen, 15 0, 17 0, 18 O; isotope of phosphorus, 32 P; isotope of sulfur, 35 S; and the like.
  • a certain isotopic-labeled compound of the present invention may be useful in studying drugs and/or a distribution of substrate tissues (e.g., assays).
  • a radioactive isotope tritium, that is, 3 H, and carbon- 14, that is, 14 C may be useful in view of ease of incorporation and means of immediate detection.
  • Substitution with heavier isotopes for example, substitution of hydrogen ( X H) with deuterium ( 2 H), may exhibit an excellent therapeutic effect on diseases by enhancing metabolic stability, such as increasing a half-life in vivo or reducing a dosage.
  • prevention may refer to all the acts, which inhibit or delay the occurrence of a disease by administering the compound represented by formula 1 of the present invention, stereoisomers thereof, or pharmaceutically acceptable salts thereof.
  • treatment may refer to all the acts, by which a symptom of an individual likely to develop or suffering from a disease gets better or takes a favorable turn by administering the compound represented by formula 1 of the present invention, stereoisomers thereof, or pharmaceutically acceptable salts thereof.
  • the compound represented by formula 1 of the present invention, stereoisomers thereof, or pharmaceutically acceptable salts thereof may show an effect of preventing or treating the PARP1 activity-associated diseases at a level similar to, substantially the same as, or higher than that of a conventionally known drug for preventing or treating the PARP1 activity-associated diseases.
  • the present invention may provide a method for preparing the compound represented by formula 1, stereoisomers thereof, or pharmaceutically acceptable salts thereof.
  • the compound represented by formula 1, stereoisomers thereof, or pharmaceutically acceptable salts thereof may be prepared according to any one method of reaction formulas 1 to 4, which may be modified to a level obvious to those skilled in the art.
  • Halo may mean F, Cl, Br or I, and each of Ri, R2, RA, RB, A, X, Y, Z and M may be substantially the same as defined in formula 1, if not specifically defined.
  • a compound of formula 1-1 may be subjected to a substitution reaction with an amine compound to prepare a compound of formula 1-2, which may be subjected to a Suzuki reaction to prepare a compound of formula 1-3, and a protecting group may be removed to prepare a compound of formula 1-4.
  • the compound of formula 1-1 may be subjected to a Suzuki reaction to prepare a compound of formula 2-1, which may be subjected to a substitution reaction with the amine compound to prepare the compound of formula 1-3, and a protecting group may be removed to prepare the compound of formula 1-4.
  • the compound of formula 1-1 may be subjected to a Suzuki reaction to prepare the compound of formula 2-1, which may be subjected to a hydrolysis reaction to prepare a compound of formula 3-1, which may be subjected to a substitution reaction with the amine compound to prepare the compound of formula 1-3, and a protecting group may be removed to prepare the compound of formula 1-4.
  • a compound of formula 4-1 and the compound of formula 1-4 may be subjected to a substitution reaction, or a compound of formula 4-2 and the compound of formula 1-4 may be subjected to a reductive amination reaction to prepare a compound of formula 4-3.
  • the cancer may be at least one selected from the group consisting of breast cancer, ovarian cancer, pancreatic cancer, prostate cancer, hematological cancer, gastrointestinal cancer such as gastric cancer or colorectal cancer, lung cancer such as small cell lung cancer or non-small cell lung cancer, and brain cancer such as glioma or glioblastoma.
  • the inflammatory disease may be at least one selected from the group consisting of rheumatoid arthritis, multiple sclerosis, Crohn's disease, ulcerative colonitis, ulcerative colitis, graft-versus-host disease (GVHD), systemic lupus erythematosus, toxic shock syndrome, osteoarthritis, and insulin-dependent diabetes mellitus.
  • GVHD graft-versus-host disease
  • the compound represented by formula 1, stereoisomers thereof, or pharmaceutically acceptable salts thereof of the present invention may show an inhibitory effect against PARP1 and may be advantageously used for preventing or treating PARP1 activity-associated diseases.
  • Mode for Invention
  • example compound 48 of 5-[2-[(5-fluoro-3-oxo-spiro[4H-l,4-benzoxazin-2,l'- cyclobutene]-6-yl)methyl]-3,6-dihydrooxazin-5-yl]-N-methyl-pyridin-2-carboxamide (0.050 g, 68.46%) in a white solid form.
  • example compound 78 of 5-[2-[(2-ethyl-8-fluoro-3-oxo-4H-quinoxalin-6-yl)methyl]-3,6- dihydrooxazin-5-yl]-6-fluoro-N-methyl-pyridin-2-carboxamide (0.070 g, 55.70%) in a white solid form.
  • example compound 88 of 5-[2-[(3,3-dimethyl-2-oxo-lH-pyrido[2,3-b][l,4]oxazin-7-yl)methyl]-3,6- dihydrooxazin-5-yl]-6-fluoro-N-methyl-pyridin-2-carboxamide (0.038 g, 51.71%) in a white solid form.
  • the PARP1/PARP2 binding ability of the test substance was measured using PARPtrapTM Assay Kit for PARP1 (BPS Bio #80584)/PARP2 (BPS Bio #78296).
  • PARP1 assay samples were treated at a concentration of 0.1 nM, 0.3 nM, 1 nM, 10 nM, 100 nM, 1,000 nM, and 10,000 nM.
  • PARP2 assay samples were treated at a concentration of 10 nM, 30 nM, 100 nM, 300 nM, 1,000 nM, 3,000 nM, and 10,000 nM. After sample treatment, the reaction was allowed to proceed for 60 minutes at room temperature, and fluorescence polarization (Ex 485 nm/Em 535 nm) was measured. 2.
  • the PARP1/PARP2 binding ability EC50 (nM) obtained according to the above experimental method is shown in a following table.
  • the compounds according to examples of the present invention exhibit an excellent inhibitory effect against PARP1 and an excellent selective inhibitory effect against PARP1.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un composé représenté par la formule 1 en tant qu'inhibiteur de PARP1, des stéréoisomères de celui-ci, des sels pharmaceutiquement acceptables de celui-ci et une composition pharmaceutique le comprenant, et un méthode de prévention ou de traitement de maladies associées à l'activité de PARP1 l'utilisant et une utilisation associée. Formule (1)
PCT/IB2025/051745 2024-02-20 2025-02-19 Composé utilisé en tant qu'inhibiteur de parp1 et composition pharmaceutique le comprenant Pending WO2025177150A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1020240024627A KR20250128449A (ko) 2024-02-20 2024-02-20 Parp1 억제제로서의 화합물 및 이를 포함하는 약학적 조성물
KR10-2024-0024627 2024-02-20

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010111626A2 (fr) * 2009-03-27 2010-09-30 Takeda Pharmaceutical Company Limited Inhibiteurs de la poly(adp-ribose)polymérase (parp)
CN116891456A (zh) * 2022-04-08 2023-10-17 上海翰森生物医药科技有限公司 杂环类衍生物抑制剂、其制备方法和应用
WO2023227052A1 (fr) * 2022-05-25 2023-11-30 西藏海思科制药有限公司 Inhibiteur de parp dérivé bicyclique et son utilisation
WO2023232069A1 (fr) * 2022-06-02 2023-12-07 成都苑东生物制药股份有限公司 Dérivé d'azaquinolinone, son procédé de préparation et son utilisation
CN117447449A (zh) * 2022-07-13 2024-01-26 南京圣和药业股份有限公司 Parp1抑制剂及其应用

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BR112022000534A2 (pt) 2019-07-19 2022-05-10 Astrazeneca Ab Inibidores de parp1
US11795158B2 (en) 2020-06-25 2023-10-24 Astrazeneca Ab Chemical compounds

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010111626A2 (fr) * 2009-03-27 2010-09-30 Takeda Pharmaceutical Company Limited Inhibiteurs de la poly(adp-ribose)polymérase (parp)
CN116891456A (zh) * 2022-04-08 2023-10-17 上海翰森生物医药科技有限公司 杂环类衍生物抑制剂、其制备方法和应用
WO2023227052A1 (fr) * 2022-05-25 2023-11-30 西藏海思科制药有限公司 Inhibiteur de parp dérivé bicyclique et son utilisation
WO2023232069A1 (fr) * 2022-06-02 2023-12-07 成都苑东生物制药股份有限公司 Dérivé d'azaquinolinone, son procédé de préparation et son utilisation
CN117447449A (zh) * 2022-07-13 2024-01-26 南京圣和药业股份有限公司 Parp1抑制剂及其应用

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