[go: up one dir, main page]

WO2025077896A1 - Inhibiteur d'adn polymérase thêta et son utilisation - Google Patents

Inhibiteur d'adn polymérase thêta et son utilisation Download PDF

Info

Publication number
WO2025077896A1
WO2025077896A1 PCT/CN2024/124519 CN2024124519W WO2025077896A1 WO 2025077896 A1 WO2025077896 A1 WO 2025077896A1 CN 2024124519 W CN2024124519 W CN 2024124519W WO 2025077896 A1 WO2025077896 A1 WO 2025077896A1
Authority
WO
WIPO (PCT)
Prior art keywords
alkyl
halogenated
ring
alkoxy
formula
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/CN2024/124519
Other languages
English (en)
Chinese (zh)
Inventor
谷晓辉
赖焜民
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.)
Shanghai Apeiron Therapeutics Co
Original Assignee
Shanghai Apeiron Therapeutics Co
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 Shanghai Apeiron Therapeutics Co filed Critical Shanghai Apeiron Therapeutics Co
Publication of WO2025077896A1 publication Critical patent/WO2025077896A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

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
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
    • 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
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems

Definitions

  • the present invention provides a compound having a structure of formula (I), a pharmaceutically acceptable salt, an isotope isomer, a stereoisomer,
  • R 1 represents -LR L ;
  • L represents a bond or a C 1 -C 6 alkylene group or a halogenated C 1 -C 6 alkylene group, wherein any alkylene group may be replaced by -NR a , -O-, hydroxyl, halogen, -C(O)-, -C(O)O-, -OC(O)-, -NR a C(O)-, -C(O)NR a -, or -S-;
  • RL represents a ring B or ring CY-ring D group
  • Ring D represents C 3 -C 6 cycloalkyl, 3-6 membered heterocyclyl or 5-10 membered heteroaryl, which is optionally substituted by 0, 1, 2 or 3 substituents selected from CN, halogen, -NR a R b , -S(O) 2 R a , C 1 -C 6 alkyl, halogenated C 1 -C 6 alkyl, hydroxy, C 1 -C 6 alkoxy, -COR a , C 1 -C 6 alkylamino;
  • RX1 , RX2 and RX3 each independently represent hydrogen, deuterium, halogen, C1 - C6 alkyl, C2 - C6 alkenyl, C2 - C6 alkynyl, C3 - C6 cycloalkyl, -ORa, oxo, hydroxy( C1 - C6 alkyl), NRaRb , CN , halogenated C1 - C6 alkyl, halogenated C1 - C6 alkoxy, -SO3Ra, -SRa , -SF5 , -C (O) Ra , -C (O)ORa, -OC(O) Ra , -OC( O ) NRaRb , -NRaCORb or -CONRaRb ;
  • X4 represents CH or N
  • X5 represents CH or N
  • X 4 and X 5 each independently represent CH or N.
  • the Cy may be arbitrarily substituted with 0, 1, 2 or 3 substituents selected from the group consisting of deuterated, halogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, -OR a , oxo, hydroxy(C 1 -C 6 alkyl), -NR a R b , CN, nitro, halogenated C 1 -C 6 alkyl, halogenated C 1 -C 6 alkoxy, -SO 3 R a , -SR a , -SF 5 , -C(O)R a , -C(O)OR a , -OC(O)R a , -OC(O)NR a R b , -NR a COR b or -CONR a R b ;
  • X1 represents CR X1 or N
  • X2 represents CR X2 or N
  • X3 represents CR X3 or N
  • RX1 , RX2 and RX3 each independently represent hydrogen, deuterium, halogen, C1 - C6 alkyl, C2 - C6 alkenyl, C2 - C6 alkynyl, C3 - C6 cycloalkyl, -ORa, oxo, hydroxy( C1 - C6 alkyl), -NRaRb , CN , nitro, C1 - C6 alkoxy, halogenated C1 - C6 alkyl, halogenated C1 - C6 alkoxy , -SO3Ra , -SRa, -SF5, -C (O) Ra , -C(O) ORa , -OC (O) Ra , -OC (O ) NRaRb , -NRaCORb or -CONRaRb .
  • ring A represents a saturated or unsaturated ring; and the ring A may contain 0, 1, 2, 3, or 4 heteroatoms selected from O, N, S, and Se; further, the ring A may be arbitrarily substituted with 0, 1, 2, or 3 substituents selected from deuterated, halogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, -OR a , oxo, hydroxyl (C 1 -C 6 alkyl), NR a R b , CN, nitro, halogenated C 1 -C 6 alkyl, halogenated C 1 -C 6 alkoxy, -SO 3 R a , -SR a , -SF 5 , -C(O)R a , -C(O)OR a , -OC(O)R a , -OC(O)NR a R
  • X1 represents CR X1 or N
  • X2 represents CR X2 or N
  • X3 represents CR X3 or N
  • X1 represents CH or N; preferably CH.
  • X 3 represents CH or N; preferably N.
  • L represents -CH 2 - or -CH 2 CH 2 -.
  • reaction solution is concentrated in vacuo to remove trifluoroacetic acid. Dissolve in ethyl acetate and adjust pH to 8 with sodium bicarbonate. Extract with ethyl acetate 3 times, 10 ml each time, and dry over anhydrous sodium sulfate. Combine the organic phases and concentrate in vacuo.
  • Step 3 Dissolve (3aR, 11aS)-6-chloro-10-methyl-1-(7-(trifluoromethyl)thiazolo[5,4-b]pyridin-5-yl)-1,3a,4,5,10,11a-hexahydro-2H-benzo[b]pyrrolo[2,3-f][1,4]diazooctane-2,11(3H)-dione (250 mg, 0.52 mmol) in N,N-dimethylformamide (4 ml), add sodium carbonate (275 mg, 2.59 mmol), tetrabutylammonium bromide (33 mg, 0.10 mmol), 3-bromoprop-1-ene (314 mg, 2.59 mmol).
  • Step 5 2-((3aR, 11aS)-6-chloro-10-methyl-2,11-dioxo-1-(7-(trifluoromethyl)thiazolo[5,4-b]pyridin-5-yl)-1,2,3,3a,4,10,11,11a-octahydro-5H-benzo[b]pyrrolo[2,3-f][1,4]diazoxifen-5-yl)acetaldehyde (80 mg, 0.15 mmol) was dissolved in methanol (2 ml) solution, and molecular sieves (10 mg) and acetic acid (92 mg, 1.53 mmol) were added. The mixture was stirred at room temperature for 30 minutes.
  • Step 3 Dissolve (3aR, 11aS)-6-chloro-10-methyl-1-(4-(trifluoromethyl)thieno[2,3-b]pyridin-6-yl)-1,3a,4,5,10,11a-hexahydro-2H-benzo[b]pyrrolo[2,3-f][1,4]diazooctane-2,11(3H)-dione (0.11 g, 0.23 mmol) in N,N-dimethylformamide solution (2.00 ml), add 3-bromopropylene (1.51 g, 12.58 mmol), sodium carbonate (0.08 g, 0.75 mmol) and tetrabutylammonium bromide (0.01 g, 0.03 mmol), and stir the reaction at 100°C for 2 hours.
  • Step 5 Dissolve 2-((3aR, 11aS)-6-chloro-10-methyl-2,11-dioxo-1-(4-(trifluoromethyl)thieno[2,3-b]pyridin-6-yl)-1,2,3,3a,4,10,11,11a-octahydro-5H-benzo[b]pyrrolo[2,3-f][1,4]diazoxazine-5-yl)acetaldehyde (60 mg, 0.11 mmol) in methanol (2.00 ml), add 1-methylpiperazine (23 mg, 0.23 mmol) and acetic acid (69 mg, 11.49 mmol) and stir at room temperature for 20 minutes, then add sodium cyanoborohydride (29 mg, 0.46 mmol) at 0°C, and then stir at room temperature for 30 minutes.
  • (R)-pyrrolidin-3-ol was used to replace 1-methylpiperazine to give (3aR, 11aS)-5-(2-((R)-3-hydroxypyrrolidin-1-yl)ethyl)-6,10-dimethyl-1-(4-(trifluoromethyl)thieno[2,3-b]pyridin-6-yl)-1,3a,4,5,10,11a-hexahydro-2H-benzo[b]pyrrolo[2,3-f][1,4]diazooctane-2,11(3H)-dione (3.21 mg, 0.18 mmol, 3.00% yield) as a white solid.
  • Example 14 Synthesis of (3aR, 11aS)-6,10-dimethyl-5-(2-(4-methylpiperazin-1-yl)ethyl)-1-(4-(trifluoromethyl)selenophenyl[2,3-b]pyridin-6-yl)-1,3a,4,5,10,11a-hexahydro-2H-benzo[b]pyrrolo[2,3-f][1,4]diazooctane-2,11(3H)-dione
  • Example 15 Synthesis of (3aR, 11aS)-5-((7-acryloyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazin-3-yl)methyl)-6,10-dimethyl-1-(4-(trifluoromethyl)thieno[2,3-b]pyridin-6-yl)-1,3a,4,5,10,11a-hexahydro-2H-benzo[b]pyrrolo[2,3-f][1,4]diazopyrimidine-2,11(3H)-dione
  • Example 16 Synthesis of (3aR, 11aS)-5-(2-(4-(1-acryloylazine-3-yl)piperazin-1-yl)ethyl)-6,10-dimethyl-1-(7-(trifluoromethyl)thiazolo[5,4-b]pyridin-5-yl)-1,3a,4,5,10,11a-hexahydro 2H-benzo[b]pyrrolo[2,3-f][1,4]diazooctane-2,11(3H)-dione
  • Step 2 3-(4-(2-((3aR, 11aS)-6,10-dimethyl-2,11-dioxo-1-(7-(trifluoromethyl)thiazole Benzyl (5,4-b]pyridin-5-yl)-1,2,3,3a,4,10,11,11a-octahydro-5H-benzo[b]pyrrolo[2,3-f][1,4]diazoxazin-5-yl)ethyl)piperazin-1-yl)azetidine-1-carboxylate (100 mg, 0.13 mmol) was dissolved in hydrochloric acid (2.00 ml) and stirred at 80° C. for 1 hour. The reaction progress was monitored by LCMS.
  • Step 1 Dissolve ((3aR, 11aS)-6-chloro-10-methyl-1-(4-(trifluoromethyl)thieno[2,3-b]pyridin-6-yl)-1,3a,4,5,10,11a-hexahydro-2H-benzo[b]pyrrolo[2,3-f][1,4]diazooctane-2,11(3H)-dione (200 mg, 0.42 mmol) in N-methylpyrrolidone (5.00 ml) and add butyl bromoacetate (812 mg, 4.16 mmol), potassium carbonate (172 mg, 1.25 mmol) and tetrabutylammonium iodide (15.4 mg, 0.04 mmol).
  • Step 2 2-((3aR,11aS)-6-chloro-10-methyl-2,11-dioxo-1-(4-(trifluoromethyl)thieno[2,3-b]pyridin-6-yl)-1,2,3,3a,4,10,11,11a-octahydro-5H-benzo[b]pyrrolo[2,3-f][1,4]diazoxazin-5-yl)acetic acid (80 mg, 0.15 mmol) was dissolved in dichloromethane (2.00 ml) and 1-methylpiperazine (30 mg, 0.30 mmol), 2-(7-azabenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate (65 mg, 0.17 mmol) and N,N-diisopropylethylamine (55 mg, 0.43 mmol) were added to the solution and stirred at room temperature for 1 hour.
  • Step 1 Dissolve 4-bromo-2,6-dichloro-3-pyridinamine (20.0 g, 82.68 mmol) in 1,4-dioxane (100.0 mL) solution, add oxyphenylmethane isothiocyanate (20.24 g, 124.02 mmol), and stir overnight at 100 ° C.
  • LCMS shows mainly product. The reactants were cooled to room temperature, concentrated, and the residue was recrystallized from dichloromethane and filtered to give N-(7-bromo-5-chloro(1,3-thiazolo[5,4-b]pyridin-2-yl))benzamide (30 g, 98%) as an off-white solid.
  • Step 3 7-bromo-5-chloro-1,3-thiazolo[5,4-b]pyridine-2-amine (20.5 g, 38.75 mmol) was dissolved in tetrahydrofuran (200.00 mL) solution, tert-butyl nitrite (11.3 g, 107.74 mmol) was added, and the mixture was stirred at 70 ° C overnight. LCMS showed that it was mainly product and the raw material was completely consumed.
  • Step 7 Dissolve [(2S,3S)-3-(hydroxymethyl)-5-oxopyrrolidin-2-yl]-N- ⁇ 2-[(tert-butoxy)carbonylamino]-3-chlorophenyl ⁇ -N-methylformamide (10.62 g, 26.64 mmol) in dichloromethane (200 mL), add triethylamine (17.8 g, 175.95 mmol), and then add methanesulfonyl chloride (6.05 g, 52.78 mmol) dropwise at 0°C. mmol). The reaction mixture was stirred at 0 ° C for 1 hour.
  • Step 9 Dissolve 5-chloro-7-(trifluoromethylthio)-1,3-thiazolin-[5,4-b]pyridine (520 mg, 1.54 mmol) in 1,4-dioxane (15.0 mL) solution, add tert-butyl (11aS, 3aR)-6-chloro-10-methyl-2,11-dioxo-4H, 11aH, 3aH-benzo [b] pyrrolo [2.3-f] 1,3-f] 1,4-diaminomole), potassium carbonate (636 mg, 4.61 mmol), 4,5-bis (diphenylphosphine) -9,9-dimethylxanthene (177.85 mg, 0.31 mmol), tris (dibenzylideneacetone) dipalladium (141 mg, 0.15 mmol).
  • Step 11 ((3aR, 11aS)-6-chloro-10-methyl-1-(7-(trifluoromethyl)thio)thiazol[5,4-b]pyridin-5-yl)-1,3a,4,5,10,11-hexahydro-2H-benzo[b]pyrrolo[2,3-f][1,4]diazo-2,11(3H)-dione (60 mg, 0.12 mmol) was dissolved in N,N-dimethylformamide (2.0 mL) solution, and 3-bromo-1-propene (70 mg, 0.58 mmol), sodium carbonate (61 mg, 0.58 mmol), and tetrabutylammonium bromide (3.7 mg, 0.01 mmol) were added.
  • Step 13 Dissolve 2- ⁇ (11aS,3aR)-6-chloro-10-methyl-2,11-dioxo-1-[7-(trifluoromethylthio)(1,3-thiazolino[4,5-e]pyridin-5-yl)]benzo[b]pyrrolidino[2,3-f]1,4-diazolidin-5-yl ⁇ ethanamine (25.0 mg, 0.04 mmol) in methanol (2.0 mL) solution, add 1-methylpiperazine (9.0 mg, 0.09 mmol) and acetic acid (1 drop). Stir the reaction at room temperature for 0.5 hours. Add sodium cyanoborohydride (4.2 mg, 0.07 mmol) and continue stirring for 0.5 hours.
  • Example 22 (3aR, 11aS)-6,10-dimethyl-5-(2-(4-methylpiperazin-1-yl)ethyl)-1-(7-(trifluoromethyl)thio)thiazo[5,4-b]pyridin-5-yl)-1,3a,4,5,11a-hexahydro-2H-benzo[b]pyrrolo[2,3-f][1,4]diazo-2,11(3H)-dione
  • Example 15 A similar method to Example 15 was used to obtain (3aR, 11aS)-6,10-dimethyl-5-(2-(4-methylpiperazin-1-yl)ethyl)-1-(7-(trifluoromethyl)thio)thiazo[5,4-b]pyridin-5-yl)-1,3a,4,5,11a-hexahydro-2H-benzo[b]pyrrolo[2,3-f][1,4]diazo-2,11(3H)-dione (10.05 mg, 35%)
  • the PicoGreen assay was used to determine the ability of compounds to inhibit Pol ⁇ polymerase activity in vitro.
  • the His-TEV-SUMO-tagged Pol ⁇ protein (amino acids 1792-2590) expressed in E. coli was purified and stored in aliquots at -80°C.
  • the assay buffer composition was 25 mM Tris HCI pH 7.5, 12.5 mM NaCI, 0.5 mM MgCI2, 5% glycerol, 0.01% Triton X-100, 0.01% BSA and 1 mM DTT.

Landscapes

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

Abstract

La présente invention concerne un inhibiteur de l'ADN polymérase thêta (Polθ) et une utilisation de clui-ci. Un composé selon la présente invention présente la structure suivante, et a un bon effet d'inhibition sur Polθ.
PCT/CN2024/124519 2023-10-12 2024-10-12 Inhibiteur d'adn polymérase thêta et son utilisation Pending WO2025077896A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CN202311323093.7 2023-10-12
CN202311323093 2023-10-12
CN202311805564.8 2023-12-25
CN202311805564 2023-12-25

Publications (1)

Publication Number Publication Date
WO2025077896A1 true WO2025077896A1 (fr) 2025-04-17

Family

ID=95396667

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2024/124519 Pending WO2025077896A1 (fr) 2023-10-12 2024-10-12 Inhibiteur d'adn polymérase thêta et son utilisation

Country Status (1)

Country Link
WO (1) WO2025077896A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2025214463A1 (fr) * 2024-04-13 2025-10-16 正大天晴药业集团股份有限公司 Composé contenant une structure tricyclique fusionnée

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023067356A1 (fr) * 2021-10-21 2023-04-27 Artios Pharma Limited Composés hétérocycliques destinés à être utilisés dans le traitement du cancer
WO2023067353A1 (fr) * 2021-10-21 2023-04-27 Artios Pharma Limited Composés hétérocycliques à utiliser dans le traitement du cancer

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023067356A1 (fr) * 2021-10-21 2023-04-27 Artios Pharma Limited Composés hétérocycliques destinés à être utilisés dans le traitement du cancer
WO2023067353A1 (fr) * 2021-10-21 2023-04-27 Artios Pharma Limited Composés hétérocycliques à utiliser dans le traitement du cancer
WO2023067355A1 (fr) * 2021-10-21 2023-04-27 Artios Pharma Limited Composés hétérocycliques destinés à être utilisés dans le traitement du cancer

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2025214463A1 (fr) * 2024-04-13 2025-10-16 正大天晴药业集团股份有限公司 Composé contenant une structure tricyclique fusionnée

Similar Documents

Publication Publication Date Title
CN110573501B (zh) Rho相关蛋白激酶抑制剂、包含其的药物组合物及其制备方法和用途
CN112094269B (zh) 一类饱和六元环并杂环类化合物、制备方法和用途
CN112469707B (zh) 脊髓性肌萎缩症的预防剂或治疗剂
KR102442235B1 (ko) 융합된 펜타시클릭 이미다졸 유도체
CN108948004B (zh) 作为fgfr4抑制剂的杂环化合物
KR102604942B1 (ko) 증식성 장애의 치료에 사용하기 위한 트리사이클릭 화합물
TW201014855A (en) Compounds for the treatment of hepatitis C
US8293909B2 (en) Compounds for the treatment of hepatitis C
CN115427035B (zh) Enl/af9 yeats抑制剂
KR20160145796A (ko) BET 단백질의 저해제로서의 1H-피롤로[2,3-c]피리딘-7(6H)-온 및 피라졸로[3,4-c]피리딘-7(6H)-온
AU2015289643A1 (en) Therapeutic inhibitory compounds
WO2012019426A1 (fr) Dérivé de phtalazinone, son procédé de préparation et utilisation pharmaceutique
AU2010212560B2 (en) Derivatives of azaindoles as inhibitors of protein kinases Abl and Src
EP2545050A1 (fr) Composés destinés au traitement de l'hépatite c
CN108290835B (zh) Alk和srpk的抑制剂和使用方法
WO2020125759A1 (fr) Composé en tant qu'inhibiteur de la voie de signalisation wnt et son utilisation médicale
WO2016100166A1 (fr) Dihydro-1h-pyrrolo[3,2-c]pyridin-4(5h)-ones substituées en tant qu'inhibiteurs de ripk3
CN110461842A (zh) 作为tnf活性调节剂的稠合五环咪唑衍生物
WO2024255765A1 (fr) Nouveaux composés, compositions les comprenant et leurs utilisations
WO2025077896A1 (fr) Inhibiteur d'adn polymérase thêta et son utilisation
CN101277689B (zh) 噻唑并嘧啶类激酶抑制剂
TWI856471B (zh) 一種DNA聚合酶theta抑制劑及其應用
AU2014243257A1 (en) Pyrazolonaphthyridinone derivatives as METAP2 inhibitors (methionine aminopeptidase type-2)
EP3436458A1 (fr) Dérivés d'imidazole pentacycliques condensés utilisés en tant que modulateurs de l'activité du tnf
EP4617273A1 (fr) Inhibiteur de parp1 tricyclique fusionné, son procédé de préparation et son utilisation

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: 24876701

Country of ref document: EP

Kind code of ref document: A1