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WO2025157979A1 - Voie de synthèse pour la préparation de 8-(1,3-diméthyl-1h-pyrazol-4-yl)-1-(sa)-(3-fluoro-5-méthoxy-pyridin-4-yl)-7-méthoxy-3-méthyl-1,3-dihydro-imidazo[4,5-c]quinoléin-2-one - Google Patents

Voie de synthèse pour la préparation de 8-(1,3-diméthyl-1h-pyrazol-4-yl)-1-(sa)-(3-fluoro-5-méthoxy-pyridin-4-yl)-7-méthoxy-3-méthyl-1,3-dihydro-imidazo[4,5-c]quinoléin-2-one

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Publication number
WO2025157979A1
WO2025157979A1 PCT/EP2025/051769 EP2025051769W WO2025157979A1 WO 2025157979 A1 WO2025157979 A1 WO 2025157979A1 EP 2025051769 W EP2025051769 W EP 2025051769W WO 2025157979 A1 WO2025157979 A1 WO 2025157979A1
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WIPO (PCT)
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compound
formula
atropisomer
salt
process according
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Pending
Application number
PCT/EP2025/051769
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English (en)
Inventor
Annunziata LANGELLA
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Merck Patent GmbH
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Merck Patent GmbH
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Publication of WO2025157979A1 publication Critical patent/WO2025157979A1/fr
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Classifications

    • 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

Definitions

  • the present invention provides a novel process for preparing 8-(1 ,3-dimethyl- 1 H-pyrazol-4-yl)-1-(Sa)-(3-fluoro-5-methoxy-pyridin-4-yl)-7-methoxy-3-methyl-1 ,3- dihydro-imidazo[4,5-c]quinolin-2-one - also known as “Lartesertib” or “M4076” - or a pharmaceutically acceptable salt thereof.
  • the ATM kinase inhibitor M4076 is an orally bioavailable ATP-competitive inhibitor of ataxia telangiectasia mutated kinase (ATM), with potential chemo-/radio- sensitizing and antineoplastic activities.
  • ATM ataxia telangiectasia mutated kinase
  • M4076 targets and binds to ATM, thereby inhibiting the kinase activity of ATM and ATM-mediated signaling. This prevents DNA damage checkpoint activation, disrupts DNA damage repair, induces tumor cell apoptosis, and leads to cell death of ATM -overexpressing tumor cells.
  • M4076 sensitizes tumor cells to chemo- and radiotherapy and increases their anti-tumor activity.
  • ATM a serine/threonine protein kinase upregulated in a variety of cancer cell types, is activated in response to DNA damage and plays a key role in DNA-strand repair.
  • M4076 is the Sa-atropisomer (also referred to as the /W-atropisomer) of 8-(1 ,3- Dimethyl-1 H-pyrazol-4-yl)-1 -(3-fluoro-5-methoxy-pyridin-4-yl)-7-methoxy-3-methyl-1 ,3- dihydro-imidazo[4,5-c]quinolin-2-one and has the following chemical formula:
  • the other atropisomer of 8-(1 ,3-Dimethyl-1 H-pyrazol-4-yl)-1-(3-fluoro-5- methoxy-pyridin-4-yl)-7-methoxy-3-methyl-1 ,3-dihydro-imidazo[4,5-c]quinolin-2-one is the Ra-atropisomer (also referred to as the P-atropisomer).
  • This compound has the following structure and is also referred to herein as Compound Z:
  • atropisomer refers to a stereoisomer which arises due to a restricted rotation around a single bond that creates a chiral axis, whereby the rotation barrier around said single bond has to be sufficiently high to permit the isolation of a single atropisomer. Said rotation barrier can result, for example, from steric interactions with other residues of the same molecule thereby restricting said rotation around said single bond. Both steric and electronic factors come into play and may reinforce or counteract one another.
  • Atropisomers are commonly regarded as a liability in drug discovery, since the stability of these isomers depends on energy differences resulting from steric strain or other factors that create a barrier to the rotation around said single bond.
  • atropisomerism cannot be readily predicted.
  • the height of said energy barrier determines the time of the interconversion of two corresponding atropisomers.
  • both atropisomers of 8-(1 ,3-Dimethyl-1 H-pyrazol-4-yl)-1-(3-fluoro-5- methoxy-pyridin-4-yl)-7-methoxy-3-methyl-1 ,3-dihydroimidazo[4,5-c]quinolin-2-one surprisingly have sufficient stability and can be used separately for drug development.
  • the Sa-atropisomer i.e. M4076
  • the Sa-atropisomer exhibits especially good properties superior to those of the Ra-atropisomer (i.e. Compound Z), e.g. in terms of its efficacy and selectivity, which make the Sa-atropisomer a very suitable candidate for development of a medicament for the treatment of cancer (see for example WO 2020/193660).
  • the process should be robust, cost-efficient, and timesaving.
  • the process of the present invention provides Compound 2 in an atropisomerically enriched form (enriched in the Sa-atropisomer relative to the Ra- atropisomer), followed by a coupling reaction to directly generate M4076.
  • the generation of the undesired Ra-atropisomer i.e. Compound Z
  • undesired atropisomers can be recycled at an early stage of the proceedings.
  • the present invention also relates to deuterated derivatives of M4076. That means that one or more hydrogen atoms of M4076 can be substituted by deuterium atoms.
  • deuterium atoms the same hydrogen atoms are also substituted in the precursor molecules, for example Compounds 1 and 2 or the boronic acid used in a Suzuki coupling reaction.
  • Fig. 1 shows a chromatogram regarding the separation of a racemic mixture of Compound 2 into the two atropisomers of Formulae 2.1 and 2.2.
  • the peak at 8.105 minutes corresponds to the atropisomer of Formula 2.2; the peak at 13.678 minutes corresponds to the atropisomer of Formula 2.1.
  • FIG. 2 shows an illustration of the process of the present invention (including selected preferred embodiments and some sub-steps; other preferred embodiments - e.g. an optional final crystallization step - have been omitted for the sake of clarity).
  • Fig. 3 shows the reactions performed by the inventors and referred to in the Examples section.
  • the inventor of the present invention has found that unlike the Ra- atropisomer of M4076 (i.e. Compound Z), the Ra-atropisomers of Compounds 1 and 2 (i.e. the compounds of Formula 1.2 and 2.2) can be racemized at moderate temperatures.
  • the present invention relates to a process for preparing M4076 or a pharmaceutically acceptable salt thereof, which is characterized in that it comprises the following steps:
  • “Atropisomerically enriched in the Sa-atropisomer of Formula 2.1” means that the Compound 2 comprises an excess of the Sa-atropisomer relative to the Ra- atropisomer”.
  • the present invention relates to a process for preparing M4076 or a pharmaceutically acceptable salt thereof, which is characterized in that no or substantially no Compound Z is produced
  • Compounds 1 and 2 show atropoisomeric behavior and can be separated into two stable atropisomers, herein described by Formulae 1.1 and 1.2 and Formula 2.1 and 2.2, respectively. Specifically, by using HPLC chiral chromatography, two well-distinguished peaks, one corresponding to the compound of Formula 2.1 (at 13.678 minutes) and the other one corresponding to the compound of Formula 2.2 (at 8.105 minutes), were detected (See Figure 1). Compound 1 could also be separated into two stable atropisomers, herein referred to by Formulae 1.1 and 1.2.
  • the inventive process uses an atropisomerically enriched Compound 2, comprising an excess of the Sa-atropisomer of Formula 2.1 relative to the Ra-atropisomer of Formula 2.2.
  • m 2 .i is the weight of the compound of Formula 2.1 .
  • m 2 2 is the weight of the compound of Formula 2.2.
  • the enantiomeric excess (ee) of the Sa-atropisomer of Formula 2.1 is at least 20%, preferably at least 30%, more preferably at least 40%, even more preferably at least 40%, even more preferably at least 50%, even more preferably at least 60%, even more preferably at least 70%, even more preferably at least 80%, even more preferably at least 90%, even more preferably at least 95%, even more preferably at least 98%, even more preferably at least 99%.
  • Compound 2 provided in step (1) of the inventive process comprises no or substantially no Ra-atropisomer of Formula 2.2.
  • substantially no refers to an amount of less than 5 wt.%, preferably less than 1 wt.%, more preferably less than 0.5 wt.%.
  • Compound 2 provided in step (1 ) of the inventive process is an atropisomerically pure compound of Formula 2.1 , wherein “atropisomerically pure” refers to a weight ratio of the Sa-atropisomer of Formula 2.1 to the Ra-atropisomer of Formula 2.2 of greater than 98 : 2, preferably greater than 99 : 1 , more preferably greater than 99.2 : 0.8, more preferably greater than 99.5 : 0.5.
  • step (2) of the process is preferably performed at a temperature below the racemization temperature of Compound 2.1 and of M4076.
  • Compound 2 reacts with a boronic ester (Compound of Formula 3) at a temperature of about 90 °C for a duration of about 35 hours to form a racemic mixture of 8-(1 ,3-Dimethyl-1 H-pyrazol-4-yl)-1-(3-fluoro- 5-methoxy-pyridin-4-yl)-7-methoxy-3-methyl-1 ,3-dihydroimidazo[4,5-c]quinolin-2-one.
  • a boronic ester Compound of Formula 3
  • process step (2) is preferably performed at a temperature below the racemization temperature and/or for rather short timeframes.
  • process step (2) is performed at a temperature of 75°C or less, preferably at a temperature of 73°C or less, more preferably at a temperature of 70°C or less, more preferably at a temperature of 65°C to 70°C, more preferably at a temperature of 68°C to 70°C.
  • a temperature of 65 °C to 70 °C and 68 °C to 70 °C a particularly good balance of reaction temperature and reaction time is achieved.
  • step (2) is performed for rather short timeframes.
  • step (2) is performed for a duration of less than 30 hours, preferably less than 20 hours, more preferably less than 10 hours, more preferably less than 5 hours, more preferably less than 3 hours.
  • step (2) It has been found that it is possible to perform step (2) in high yields at such low temperatures and short reaction times.
  • process step (2) is a Suzuki coupling reaction, wherein Compound 3 is used
  • step (2) is performed in the presence of a PdCl2(PPh) 3 )2 catalyst.
  • KOH is used as a base in step (2).
  • acetonitrile is used as a solvent in step (2).
  • the existing manufacturing process uses a dioxane/H 2 O mixture as a solvent, K 2 CO 3 as a base, and Pd(PPh 3 ) 4 as a catalyst and uses rather high temperatures (about 90 °C) and long reaction times (more than 30 hours).
  • a racemic mixture of Compound 2 can be provided and perform a chiral resolution step for separating said racemic mixture of Compound 2 into (a) a Compound 2 that is atropisomerically enriched in the Sa-atropisomer of Formula 2.1 , and (b) a Compound 2 that is atropisomerically enriched in the Ra-atropisomer of Formula 2.2.
  • Fraction (a) can then be used for synthesizing M4076 in atropisomerically enriched form; fraction (b) can be racemized at moderate temperature and recycled to the process.
  • the Compound 1 that is atropisomerically enriched in the Ra-atropisomer of Formula 1.2 can then be racemized at moderate temperature (see above) and recycled into the process.
  • the inventive process comprises
  • step (1) (i) a step (A) performed prior to step (1) or (ii) steps (a) and (P) performed prior to step (1).
  • Step (A) is a chiral resolution step of separating a racemic mixture of Compound 2 into (a) a Compound 2 that is atropisomerically enriched in the Sa- atropisomer of Formula 2.1 , thereby obtaining the Compound 2 provided in step (1), and (b) a Compound 2 that is atropisomerically enriched in the Ra-atropisomer of Formula 2.2.
  • the enantiomeric excess (ee) of the Sa-atropisomer of Formula 2.1 is at least 20%, preferably at least 30%, more preferably at least 40%, even more preferably at least 40%, even more preferably at least 50%, even more preferably at least 60%, even more preferably at least 70%, even more preferably at least 80%, even more preferably at least 90%, even more preferably at least 95%, even more preferably at least 98%, even more preferably at least 99%.
  • the Compound 2 that is atropisomerically enriched in the Sa- atropisomer of Formula 2.1 , as obtained in step (A), comprises no or substantially no Ra- atropisomer of Formula 2.2.
  • substantially no refers to an amount of less than 5 wt.%, preferably less than 1 wt.%, more preferably less than 0.5 wt.%, based on the total weight of the compounds of Formula 2.1 and 2.2.
  • Step (A) preferably comprises the following sub-steps:
  • Step (A1) is preferably performed by reacting the compounds of Formula 2.1 and 2.2 in the racemic mixture with (S,S)-di-p-anisoyltartaric acid.
  • Step (A2) is preferably performed by filtration.
  • Step (A3) is preferably performed by reacting salt A with a base, preferably K2CO3.
  • the compound of Formula 2.2 can be racemized by applying heat.
  • the Compound 2 that is atropisomerically enriched in the Ra-atropisomer of Formula 2.2, as obtained in step (A) is racemized and recycled to the process.
  • step (A) the Compound 2 that is atropisomerically enriched in the Ra- atropisomer of Formula 2.2 as obtained in step (A) is converted into a racemic mixture of Compound 2, and the thus obtained racemic mixture of Compound 2 is then subjected to step (A). And so on, and so forth.
  • This conversion is preferably performed by converting salt B as obtained in step (A2) back to the compound of Formula 2.2, followed by a racemization of the thus obtained compound of Formula 2.2, thereby producing a racemic mixture of Compound 2.
  • said conversion of salt B back to the compound of Formula 2.2 is performed by reacting salt B with a base, preferably K2CO3.
  • the racemization of the compound of Formula 2.2 is preferably performed by heating the compound of Formula 2.2 above its racemization temperature, preferably to a temperature of 120°C to 140°C.
  • step (A) further comprises a recrystallization step (A2.1) performed after step (A2) and before step (A3).
  • the recrystallization step (A2.1) comprises a recrystallization of salt A obtained in step (A2), thereby obtaining a recrystallized salt A. It is to be understood that if the recrystallization step (A2.1) is performed, the recrystallized salt A is converted back to the compound of Formula 2.1 in step (A3).
  • Step (a) is a chiral resolution step of separating a racemic mixture of Compound 1 into (a) a Compound 1 that is atropisomerically enriched in the Sa-atropisomer of Formula 1.1 , and (b) a Compound 1 that is atropisomerically enriched in the Ra- atropisomer of Formula 1.2.
  • the Compound 1 that is atropisomerically enriched in the Sa- atropisomer of Formula 1.1 , as obtained in step (a), comprises no or substantially no Ra- atropisomer of Formula 1 .2.
  • substantially no refers to an amount of less than 5 wt.%, preferably less than 1 wt.%, more preferably less than 0.5 wt.%, based on the total weight of the compounds of Formula 2.1 and 2.2.
  • Step (a) preferably comprises the following sub-steps:
  • Step (a1) is preferably performed by reacting the compounds of Formula 1.1 and 1 .2 in the racemic mixture of Compound 1 with (S,S)-di-p-anisoyltartaric acid.
  • Step (a2) is preferably performed by filtration.
  • Step (a3) is preferably performed by reacting salt C with a base, preferably K 2 CO 3 .
  • the compound of Formula 1.2 can be racemized by applying heat.
  • the Compound 1 that is atropisomerically enriched in the Ra-atropisomer of Formula 1 .2, as obtained in step (a) is recycled to the process.
  • the Compound 1 that is atropisomerically enriched in the Ra- atropisomer of Formula 1.2 as obtained in step (a), is converted into a racemic mixture of Compound 1 , and the thus obtained racemic mixture of Compound 1 is then subjected to step (a). And so on, and so forth.
  • This conversion is preferably performed by converting salt D as obtained in step (a 2) back to the compound of Formula 1.2, followed by a racemization of the thus obtained compound of Formula 1.2, thereby producing a racemic mixture of Compound 1 .
  • said conversion of salt D back to the compound of Formula 1.2 is performed by reacting salt D with a base, preferably K2CO3.
  • the racemization of the compound of Formula 1.2 is preferably performed by heating the compound of Formula 1.2 above its racemization temperature, preferably to a temperature of 120°C to 140°C.
  • step (a) further comprises a recrystallization step (a2.1) performed after step (a2) and before step (a3).
  • the recrystallization step (a2.1) comprises a recrystallization of salt C obtained in step (a2), thereby obtaining a recrystallized salt C. It is to be understood that if the recrystallization step (a2.1) is performed, the recrystallized salt C is converted back to the compound of Formula 1.1 in step (a3).
  • Step (p) is preferably performed by a reaction with methyl iodide.
  • step (p) is performed at a temperature below the racemization temperature, preferably room temperature.
  • the inventive process further comprises a step (3), wherein step (3) is a final crystallization step.
  • the present invention also relates to a process for preparing M4076, or a pharmaceutically acceptable salt thereof, the process being characterized in that no or substantially no Compound Z is produced in the process.
  • substantially no refers to an amount of less than 5 wt.%, preferably less than 1 wt.%, more preferably less than 0.5 wt.%, based on the total weight of Compounds M4076 and Z.
  • This process preferably comprises steps (1) and (2) of the above-described process.
  • ee [(I m 2 .i - m 2 2 1) I (m 2 .i + m 2 2 )
  • Item 4 Process according to Item 3, wherein “substantially no” refers to an amount of less than 5 wt.%, preferably less than 1 wt.%, more preferably less than 0.5 wt.%, based on the total weight of the compounds of Formula 2.1 and 2.2.
  • step (2) is performed at a temperature below the racemization temperature of the compound of Formula 2.1 and of M4076, preferably at a temperature of 75°C or less, preferably at a temperature of 73°C or less, more preferably at a temperature of 70°C or less, more preferably at a temperature of 65°C to 70°C, more preferably at a temperature of 68°C to 70°C.
  • Item 6. Process according to any one of the preceding Items, wherein step (2) is performed for a duration of less than 30 hours, preferably less than 20 hours, more preferably less than 10 hours, more preferably less than 5 hours, more preferably less than 3 hours.
  • Item 7. Process according to any one of the preceding Items, wherein step (2) is performed at a temperature of 68°C to 70°C and a duration of less than 3 hours.
  • step (2) is a suzuki coupling reaction, wherein preferably Compound 3 is used in the Suzuki coupling reaction
  • step (2) is performed in the presence of a PdCl2(PPh) 3 )2 catalyst.
  • Item 10 Process according to any one of the preceding Items, wherein KOH is used as a base in step (2).
  • Item 11 Process according to any one of the preceding Items, wherein acetonitrile is used as a solvent in step (2).
  • step (2) is performed in acetonitrile solution and in the presence of KOH and PdCl2(PPh) 3 )2.
  • step (i) a step (A) performed prior to step (1), wherein step (A) is a chiral resolution step of separating a racemic mixture of Compound 2 into (a) a Compound 2 that is atropisomerically enriched in the Sa-atropisomer of Formula 2.1 , thereby obtaining the Compound 2 provided in step (1), and (b) a Compound 2 that is atropisomerically enriched in the Ra-atropisomer of Formula 2.2 Formula 2.2,
  • step (ii) steps (a) and (p) performed prior to step (1), wherein step (a) is a chiral resolution step of separating a racemic mixture of Compound 1 into (a) a Compound 1 that is atropisomerically enriched in the Sa- atropisomer of Formula 1.1
  • step (A) is a step of converting the Compound 1 that is atropisomerically enriched in the Sa-atropisomer of Formula 1.1 into the Compound 2 that is atropisomerically enriched in the Sa-atropisomer of Formula 2.1 provided in step (1).
  • step (A) comprises the steps of:
  • step (A1) is performed by reacting the compounds of Formula 2.1 and 2.2 in the racemic mixture of Compound 2 with (S,S)- di-p-anisoyltartaric acid.
  • step (A2) is performed by filtration.
  • step (A3) is performed by reacting salt A with a base, preferably K2CO3.
  • Item 18 Process according to any one of Items 13 to 17, further comprising a step of recycling Compound 2 that is atropisomerically enriched in the Ra-atropisomer of Formula 2.2 to the process.
  • Item 20 Process according to Item 19, wherein said conversion is performed by converting salt B as obtained in step (A2) to the compound of Formula 2.2, followed by a racemization of the thus obtained compound of Formula 2.2, thereby producing a racemic mixture of Compound 2.
  • Item 21 Process according to Item 20, wherein said conversion of salt B to the compound of Formula 2.2 is performed by reacting salt B with a base, preferably K2CO3.
  • Item 22 Process according to Item 20 or 21 , wherein said racemization of the compound of Formula 2.2 is performed by heating the compound of Formula 2.2 above its racemization temperature, preferably to a temperature of 120°C to 140°C.
  • step (a) comprises the steps of:
  • step (a1) is performed by reacting the compounds of Formula 1.1 and 1.2 in the racemic mixture of Compound 1 with (S,S)-di-p-anisoyltartaric acid.
  • Item 25 Process according to Item 23 or 24, wherein step (a2) is performed by filtration.
  • step (a3) is performed by reacting salt C with a base, preferably K2CO3.
  • Item 27 Process according to any one of Items 13 and 23 to 26, further comprising a step of recycling Compound 1 that is atropisomerically enriched in the Ra-atropisomer of Formula 1 .2 to the process.
  • Item 28 Process according to Item 27, wherein said step of recycling comprises the conversion of Compound 1 that is atropisomerically enriched in the Ra- atropisomer of Formula 1 .2 into a racemic mixture of Compound 1 , and subjecting the thus-obtained racemic mixture of Compound 1 to step (a).
  • Item 29 Process according to Item 28, wherein said conversion is performed by converting salt D as obtained in step (a2) to the compound of Formula 1.2, followed by a racemization of the thus obtained compound of Formula 1.2, thereby producing a racemic mixture of Compound 1 .
  • Item 30 Process according to Item 29, wherein said conversion of salt D to the compound of Formula 1.2 is performed by reacting salt D with a base, preferably K2CO3.
  • Item 31 Process according to Item 29 or 30, wherein said racemization of the compound of Formula 1.2 is performed by heating the compound of Formula 1.2 above its racemization temperature, preferably to a temperature of 120°C to 140°C.
  • Item 32 Process according to any one of Items 13 and 22-31 , wherein step (p) is performed by a reaction with methyl iodide.
  • step (p) is performed at a temperature below the racemization temperature, preferably room temperature.
  • Item 34 Process according to any one of Items 1 to 33, wherein one or more hydrogens are substituted by deuterium.
  • Item 36 Process according to Item 35, wherein “substantially no” refers to an amount of less than 5 wt.%, preferably less than 1 wt.%, more preferably less than 0.5 wt.%, based on the total weight of Compounds M4076 and Z.
  • Item 37 Process according to Item 35 or 36, wherein one or more hydrogens are substituted by deuterium.
  • the yield of the desired atropisomer of Formula 2.1 could be increased to more than 69% by recycling the undesired atropisomer of Formula 2.2.
  • 6-Bromo-N-(3-fluoro-5-methoxy-4-pyridyl)-7-methoxy-3-nitro-quinolin-4-amine (990 mg, 2.20 mmol) dissolved in methanol (100 ml_) is provided under a protective nitrogen atmosphere. Then, Raney-Ni (100 mg, 1.17 mmol) is added to the solution, and the reaction mixture is stirred for 30 minutes under a hydrogen atmosphere at normal pressure. After introducing nitrogen, the suspension is filtered and the filtrate dried under vacuum. The filtrate is evaporated to dryness under vacuum.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un nouveau procédé amélioré pour la préparation de M4076.
PCT/EP2025/051769 2024-01-26 2025-01-24 Voie de synthèse pour la préparation de 8-(1,3-diméthyl-1h-pyrazol-4-yl)-1-(sa)-(3-fluoro-5-méthoxy-pyridin-4-yl)-7-méthoxy-3-méthyl-1,3-dihydro-imidazo[4,5-c]quinoléin-2-one Pending WO2025157979A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP24154179.6 2024-01-26
EP24154179 2024-01-26

Publications (1)

Publication Number Publication Date
WO2025157979A1 true WO2025157979A1 (fr) 2025-07-31

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PCT/EP2025/051769 Pending WO2025157979A1 (fr) 2024-01-26 2025-01-24 Voie de synthèse pour la préparation de 8-(1,3-diméthyl-1h-pyrazol-4-yl)-1-(sa)-(3-fluoro-5-méthoxy-pyridin-4-yl)-7-méthoxy-3-méthyl-1,3-dihydro-imidazo[4,5-c]quinoléin-2-one

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016155884A1 (fr) 2015-04-02 2016-10-06 Merck Patent Gmbh Imidazolonylquinoléines et leur utilisation comme inhibiteurs des kinases atm
WO2020193660A1 (fr) 2019-03-27 2020-10-01 Merck Patent Gmbh Composés d'imidazolonylquinoline et leurs utilisations thérapeutiques

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016155884A1 (fr) 2015-04-02 2016-10-06 Merck Patent Gmbh Imidazolonylquinoléines et leur utilisation comme inhibiteurs des kinases atm
WO2020193660A1 (fr) 2019-03-27 2020-10-01 Merck Patent Gmbh Composés d'imidazolonylquinoline et leurs utilisations thérapeutiques

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