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WO2025201511A1 - Dérivé d'indazole et son procédé de préparation et son utilisation - Google Patents

Dérivé d'indazole et son procédé de préparation et son utilisation

Info

Publication number
WO2025201511A1
WO2025201511A1 PCT/CN2025/085719 CN2025085719W WO2025201511A1 WO 2025201511 A1 WO2025201511 A1 WO 2025201511A1 CN 2025085719 W CN2025085719 W CN 2025085719W WO 2025201511 A1 WO2025201511 A1 WO 2025201511A1
Authority
WO
WIPO (PCT)
Prior art keywords
mmol
compound
added
mixture
ring
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/CN2025/085719
Other languages
English (en)
Chinese (zh)
Inventor
鲍子扬
葛晓郡
陈磊
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 JINGXIN BIOMEDICAL CO Ltd
Zhejiang Jingxin Pharmaceutical Co Ltd
Original Assignee
SHANGHAI JINGXIN BIOMEDICAL CO Ltd
Zhejiang Jingxin Pharmaceutical Co Ltd
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 JINGXIN BIOMEDICAL CO Ltd, Zhejiang Jingxin Pharmaceutical Co Ltd filed Critical SHANGHAI JINGXIN BIOMEDICAL CO Ltd
Publication of WO2025201511A1 publication Critical patent/WO2025201511A1/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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A61K31/416—1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • 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
    • 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 belongs to the field of medicine, and in particular relates to indazole derivatives and preparation methods and applications thereof.
  • Parkinson's disease is the second most common neurodegenerative disorder. Its pathological changes primarily involve progressive degeneration of dopaminergic neurons in the substantia nigra and the formation of Lewy bodies. Clinical manifestations include motor symptoms such as tremor, rigidity, bradykinesia, and postural balance disorders, as well as non-motor symptoms such as sleep disturbances, olfactory disturbances, autonomic dysfunction, and cognitive and psychiatric impairments. With disease progression, both motor and non-motor symptoms of Parkinson's disease gradually worsen, impairing patients' daily activities while also imposing a significant social and medical burden.
  • LRRK2 Leucine-Rich Repeat Kinase 2
  • ROC GTPase-like ROC
  • COR C-terminal of ROC
  • LRRK2 kinase inhibitors can protect neurons from neurodegeneration induced by LRRK2 overactivation, block the increased aggregation of ⁇ -synuclein in neurons, inhibit the formation of inclusion bodies, and slow the progression of Parkinson's disease. Therefore, LRRK2 is considered a very promising target for the treatment of Parkinson's disease.
  • the indazole derivatives of the present invention may be compounds of Formula I or Formula II, or pharmaceutically acceptable salts, prodrugs, solvates, hydrates, tautomers, or stereoisomers thereof, wherein the structural formula of Formula I or Formula II is as follows:
  • Ring A, Ring B, and Ring C are each independently selected from a cycloalkyl group, a heterocyclyl group, an aryl group, or a heteroaryl group, and optionally they may be further substituted by one or more substituents;
  • R 1 , R 2 , R 3 , and R 4 are each independently selected from hydrogen, halogen, nitro, hydroxy, mercapto, cyano, amino, alkyl, haloalkyl, hydroxyalkyl, alkoxy, hydroxyalkoxy, haloalkoxy, acyl, acylamino, ester, cycloalkyl, heterocyclyl, aryl, or heteroaryl, which may be further substituted with one or more substituents;
  • ring A is selected from a cycloalkyl group or a heterocyclyl group, and the cycloalkyl group or heterocyclyl group is a spiro ring, a fused ring or a bridged ring, and optionally it may be further substituted by one or more substituents;
  • ring A is selected from 3-10 membered cycloalkyl or 3-10 membered heterocyclyl, and the 3-10 membered cycloalkyl or 3-10 membered heterocyclyl is a spiro ring, a fused ring or a bridged ring, which may be further substituted by one or more substituents;
  • Ring A is selected from:
  • X 1 , X 7 , X 13 , and X 18 are each independently selected from N or CR 11 ;
  • X2 , X3 , X4 , X5, X6 , X8 , X9 , X10 , X11 , X12 , X14 , X15 , X16 , X17 , X19 , X20 , X21 , and X22 are each independently selected from -O-, -C(O)-, -C ( R12 ) 2- , or -N( R13 )-;
  • n1, n2, n3, n4, n5, n6, n7, n8 are each independently selected from 0, 1 or 2;
  • n9 and n10 are independently selected from 1, 2 or 3;
  • R5 , R6 , R7 , R8, R9 , R10 , R11 , R12 , and R13 are each independently selected from hydrogen , halogen, nitro, hydroxy, thiol, cyano, amino, alkyl, haloalkyl, hydroxyalkyl, alkoxy, hydroxyalkoxy, haloalkoxy, acyl, acylamino, ester, cycloalkyl, heterocyclyl, aryl, or heteroaryl, which may be further substituted by one or more substituents;
  • Ring A is selected from:
  • X 2 , X 3 , X 4 , X 5 , X 6 , X 8 , X 9 , X 10 , X 11 , X 12 , X 14 , X 15 , X 16 , X 17 , X 19 , X 20 , X 21 , X 22 , n1 , n2 , n3 , n4 , n5 , n6 , n7 , n8 , n9 , n10 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , and R 13 are as defined herein;
  • n1, n2, and n4 are 1, and n3 is 2;
  • n1, n2, and n3 are 1, and n4 is 2;
  • n2 and n3 are 2, and n1 and n4 are 1;
  • n1, n2, and n4 are 2, and n3 is 1;
  • n1, n2, n3, and n4 are all 2;
  • n5 and n8 are 1, and n6 and n7 are 0;
  • n5 and n6 are 2, and n7 and n8 are 1;
  • n5 and n7 are 2, and n6 and n8 are 1;
  • n9 is 2;
  • n10 is 1;
  • n10 is 2;
  • n10 is 3;
  • the carbon atom connected to the substituent R 5 is a chiral carbon
  • the chirality of the carbon atom can be R or S
  • the carbon atom connected to the substituent R 8 is a chiral carbon
  • the chirality of the carbon atom can be R or S
  • the carbon atom connected to the substituent R 9 is a chiral carbon
  • the chirality of the carbon atom can be R or S
  • the two substituents R 12 in -C(R 12 ) 2 - may be the same or different.
  • the chirality of the carbon atom may be R or S.
  • n1, n2, n3, n4, n5, n6, n7 and/or n8 are 2, wherein the repeating units X 2 , X 3 , X 5 , X 6 , X 8 , X 9 , X 11 and/or X 12 as defined herein may be the same or different;
  • Ring A is selected from:
  • Ring B is selected from aryl or heteroaryl, which may optionally be further substituted with one or more substituents;
  • Ring B is selected from:
  • Ring B is selected from:
  • Ring C is selected from:
  • R 18 , R 19 , R 20 , R 21 , R 22 , R 23 , R 24 , R 25 , and R 26 are each independently selected from hydrogen, halogen, nitro, hydroxy, thiol, cyano, amino, alkyl, haloalkyl, hydroxyalkyl, alkoxy, hydroxyalkoxy, haloalkoxy, acyl, acylamino, ester, cycloalkyl, heterocyclyl, aryl, or heteroaryl, which may be further substituted by one or more substituents;
  • ring C is selected from 3-10 membered cycloalkyl or 3-10 membered heterocyclyl, which may be further substituted with one or more substituents;
  • Ring C is selected from:
  • the hydrogen, halogen, nitro, hydroxyl, thiol, cyano, amino, alkyl, haloalkyl, hydroxyalkyl, alkoxy, hydroxyalkoxy, haloalkoxy, acyl, acylamino, ester, cycloalkyl, heterocyclyl, aryl or heteroaryl groups may be further substituted with one or more substituents selected from hydrogen, halogen, nitro, hydroxyl, thiol, cyano, amino, alkyl, haloalkyl, hydroxyalkyl, alkoxy, hydroxyalkoxy, haloalkoxy, acyl, acylamino, ester, cycloalkyl, heterocyclyl, aryl or heteroaryl groups;
  • the hydrogen, halogen, nitro, hydroxyl, thiol, cyano, amino, alkyl, haloalkyl, hydroxyalkyl, alkoxy, hydroxyalkoxy, haloalkoxy, acyl, acylamino, ester, cycloalkyl, heterocyclyl, aryl or heteroaryl is preferably hydrogen, halogen, nitro, hydroxyl, thiol, cyano, amino, C1-10 alkyl, C1-10 haloalkyl, C1-10 hydroxyalkyl, C1-10 alkoxy, C1-10 hydroxyalkoxy, C1-10 haloalkoxy, C1-10 acyl, C1-10 acylamino, C1-10 ester, 3-10 membered cycloalkyl, 3-10 membered heterocyclyl, 6-10 membered aryl or 5-10 membered heteroaryl;
  • R 2 is selected from hydrogen, halogen, alkyl, haloalkyl, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, which may be further substituted with one or more substituents;
  • R 2 is selected from hydrogen, halogen, C1-10 alkyl, C1-10 haloalkyl, C1-10 hydroxyalkyl, 3-10 membered cycloalkyl, 3-10 membered heterocyclyl, 6-10 membered aryl, or 5-10 membered heteroaryl, which may optionally be further substituted with one or more substituents;
  • R 14 is selected from hydrogen, halogen, hydroxy, alkyl, haloalkyl, hydroxyalkyl, alkoxy, hydroxyalkoxy, haloalkoxy, cycloalkyl, heterocyclyl, aryl, or heteroaryl, which may be further substituted with one or more substituents;
  • R 14 is selected from hydrogen, halogen, hydroxy, C1-10 alkyl, C1-10 haloalkyl, C1-10 hydroxyalkyl, C1-10 alkoxy, C1-10 hydroxyalkoxy, C1-10 haloalkoxy, 3-10 membered cycloalkyl, 3-10 membered heterocyclyl, 6-10 membered aryl, or 5-10 membered heteroaryl, which may be further substituted with one or more substituents;
  • R 22 is selected from hydrogen, halogen, hydroxy, alkyl, haloalkyl, hydroxyalkyl, alkoxy, hydroxyalkoxy, haloalkoxy, cycloalkyl, heterocyclyl, aryl, or heteroaryl, which may be further substituted with one or more substituents;
  • R 22 is selected from hydrogen, halogen, hydroxy, C1-10 alkyl, C1-10 haloalkyl, C1-10 hydroxyalkyl, C1-10 alkoxy, C1-10 hydroxyalkoxy, C1-10 haloalkoxy, 3-10 membered cycloalkyl, 3-10 membered heterocyclyl, 6-10 membered aryl, or 5-10 membered heteroaryl, which may be further substituted with one or more substituents;
  • R 23 is selected from hydrogen, halogen, hydroxy, alkyl, haloalkyl, hydroxyalkyl, alkoxy, hydroxyalkoxy, haloalkoxy, cycloalkyl, heterocyclyl, aryl, or heteroaryl, which may be further substituted with one or more substituents;
  • R 23 is selected from hydrogen, halogen, hydroxy, C1-10 alkyl, C1-10 haloalkyl, C1-10 hydroxyalkyl, C1-10 alkoxy, C1-10 hydroxyalkoxy, C1-10 haloalkoxy, 3-10 membered cycloalkyl, 3-10 membered heterocyclyl, 6-10 membered aryl, or 5-10 membered heteroaryl, which may be further substituted with one or more substituents;
  • R 26 is selected from hydrogen, alkyl, haloalkyl, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, which may be further substituted with one or more substituents;
  • R 26 is selected from hydrogen, C1-10 alkyl, C1-10 haloalkyl, C1-10 hydroxyalkyl, 3-10 membered cycloalkyl, 3-10 membered heterocyclyl, 6-10 membered aryl, or 5-10 membered heteroaryl, which may be further substituted with one or more substituents;
  • the present invention further provides a compound of Formula I-1 or Formula II-1, or a pharmaceutically acceptable salt, prodrug, solvate, hydrate, tautomer, or stereoisomer thereof, wherein the structural formula of Formula I-1 or Formula II-1 is as follows:
  • the present invention further provides a compound of Formula I-2 or Formula II-2 or a pharmaceutically acceptable salt, prodrug, solvate, hydrate, tautomer, or stereoisomer thereof, wherein the structural formula of Formula I-2 or Formula II-2 is as follows:
  • the present invention further provides a compound of Formula I-3 or Formula II-3 or a pharmaceutically acceptable salt, prodrug, solvate, hydrate, tautomer, or stereoisomer thereof, wherein the structural formula of Formula I-3 or Formula II-3 is as follows:
  • R 5 is H
  • R 6 is H
  • the carbon atom connected to the substituent R 5 is a chiral carbon
  • the chirality of the carbon atom can be R or S
  • the carbon atom connected to the substituent R 6 is a chiral carbon
  • the chirality of the carbon atom can be R or S
  • R 22 is H or hydroxyalkyl; preferably C1-10 hydroxyalkyl; more preferably hydroxymethyl;
  • the present invention also relates to a pharmaceutical composition comprising the indazole derivative of the present invention.
  • the present invention also relates to the use of a compound of Formula I or Formula II or a pharmaceutically acceptable salt, prodrug, solvate, hydrate, tautomer, or stereoisomer thereof for treating Parkinson's disease (PD) or for preparing a medicament for treating Parkinson's disease (PD).
  • a compound of Formula I or Formula II or a pharmaceutically acceptable salt, prodrug, solvate, hydrate, tautomer, or stereoisomer thereof for treating Parkinson's disease (PD) or for preparing a medicament for treating Parkinson's disease (PD).
  • Non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, n-heptyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 5-methylhexyl,
  • cycloalkyl refers to a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon substituent.
  • the cycloalkyl group may contain 3 to 20 ring carbon atoms ("3-20 membered cycloalkyl”), preferably 3 to 12 ring carbon atoms ("3-12 membered cycloalkyl”), further preferably 3 to 10 ring carbon atoms (“3-10 membered cycloalkyl”), more preferably 3 to 8 ring carbon atoms (“3-8 membered cycloalkyl”), and most preferably 3 to 6 ring carbon atoms ("3-6 membered cycloalkyl”).
  • Non-limiting examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptatrienyl, cyclooctyl, and the like;
  • heterocyclyl refers to a saturated or partially unsaturated monocyclic or polycyclic hydrocarbon substituent containing the specified number of ring atoms and including at least one heteroatom selected from N, O and S as a ring member of the cycloalkyl ring.
  • the heterocyclyl group may contain 3 to 20 ring atoms ("3-20 membered heterocyclyl”), preferably 3 to 12 ring atoms ("3-12 membered heterocyclyl”), further preferably 3 to 10 ring atoms ("3-10 membered heterocyclyl”), more preferably 3 to 8 ring atoms ("3-8 membered heterocyclyl”), and most preferably 3 to 6 ring atoms ("3-6 membered heterocyclyl”).
  • Non-limiting examples of heterocyclyl groups include oxiranyl, tetrahydrofuranyl, tetrahydropyrrolyl, tetrahydropyranyl, tetrahydrothiopyranyl, piperidinyl, and the like;
  • aryl refers to an optionally substituted monocyclic, biaryl, or fused bicyclic or polycyclic ring system having the well-known characteristics of aromaticity, wherein at least one ring contains a completely conjugated ⁇ -electron system.
  • an aryl group contains 6 to 20 carbon atoms ("6-20 membered aryl") as ring members, preferably 6 to 14 carbon atoms (“6-14 membered aryl”) or more preferably 6 to 10 carbon atoms ("6-10 membered aryl”).
  • Fused aryl groups can include an aryl ring fused to another aryl ring or an aryl ring fused to a saturated or partially unsaturated carbocyclic or heterocyclic ring.
  • the point of attachment to the base molecule on such a fused aryl ring system can be a C atom of the aromatic portion of the ring system or a C or N atom of the non-aromatic portion.
  • aryl groups include, but are not limited to, phenyl, biphenyl, naphthyl, anthracenyl, phenanthrenyl, indanyl, indenyl, benzo[d][1,3]dioxole, and tetrahydronaphthyl;
  • cyano refers to -CN
  • RuPhos Pd G3 (2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl)(2-amino-1,1'-biphenyl-2-yl)palladium(II) methanesulfonate
  • reaction solution was poured into 50 mL of water and extracted with ethyl acetate (40 mL ⁇ 3). The organic phase was dried over anhydrous sodium sulfate and concentrated. The product was separated and purified by normal phase liquid chromatography to obtain about 35 mg of a crude product. The product was separated and purified by preparative liquid chromatography to obtain compound 9 (10 mg, yield 5.7%) and compound 10 (9.78 mg, yield 6%).
  • reaction mixture 43f (10 mg), 1c (12 mg), CuI (4 mg, 0.021 mmol), K 3 PO 4 (18 mg, 0.083 mmol), and methyl[(1S,2S)-2-(methylamino)cyclohexyl]amine (3 mg, 0.021 mmol) was added 2 mL of DMSO, and the mixture was degassed under nitrogen and reacted at 120° C. for 3 h. The reaction was monitored by TLC, and quenched by the addition of 20 mL of water. The reaction was extracted three times with ethyl acetate, and the organic layers were combined, dried over anhydrous sodium sulfate, and concentrated. The mixture was purified by preparative liquid separation (0.01% TFA/ACN) to afford compound 43 trifluoroacetate (1.75 mg) and compound 44 trifluoroacetate (1.2 mg).
  • Compound 52 was prepared according to Example 183 in the patent specification of WO2017012576A1.
  • the compound was diluted with DMSO (manufacturer: Sigma, catalog number: D4540).
  • SYSTEM transfer 40 nL of compound into a 384-reaction plate.

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

Abstract

La présente invention concerne un dérivé d'indazole et son procédé de préparation et son utilisation. Le dérivé d'indazole peut être utilisé pour l'inhibition de la kinase LRRK2 ou pour le traitement de la maladie de Parkinson (PD).
PCT/CN2025/085719 2024-03-29 2025-03-28 Dérivé d'indazole et son procédé de préparation et son utilisation Pending WO2025201511A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202410381526 2024-03-29
CN202410381526.2 2024-03-29

Publications (1)

Publication Number Publication Date
WO2025201511A1 true WO2025201511A1 (fr) 2025-10-02

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Application Number Title Priority Date Filing Date
PCT/CN2025/085719 Pending WO2025201511A1 (fr) 2024-03-29 2025-03-28 Dérivé d'indazole et son procédé de préparation et son utilisation

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Country Link
WO (1) WO2025201511A1 (fr)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108137510A (zh) * 2015-07-23 2018-06-08 葛兰素史密斯克莱知识产权发展有限公司 化合物
WO2019074810A1 (fr) * 2017-10-11 2019-04-18 Merck Sharp & Dohme Corp. Dérivés d'indazolyl-spiro [2,3] hexane-carbonitrile comme inhibiteurs de lrrk2, compositions pharmaceutiques, et utilisations de ceux-ci
WO2019074809A1 (fr) * 2017-10-11 2019-04-18 Merck Sharp & Dohme Corp. Dérivés d'indazolyl-spiro [2.2] pentane-carbonitrile en tant qu'inhibiteurs de lrrk2, compositions pharmaceutiques et leurs utilisations
CN110402247A (zh) * 2017-01-25 2019-11-01 葛兰素史密斯克莱知识产权发展有限公司 化合物
CN110446700A (zh) * 2017-01-25 2019-11-12 葛兰素史密斯克莱知识产权发展有限公司 化合物
WO2023283606A1 (fr) * 2021-07-08 2023-01-12 Dana-Farber Cancer Institute, Inc. Agents de dégradation de formes mutantes et de type sauvage de lrrk2 et leurs utilisations

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108137510A (zh) * 2015-07-23 2018-06-08 葛兰素史密斯克莱知识产权发展有限公司 化合物
CN110402247A (zh) * 2017-01-25 2019-11-01 葛兰素史密斯克莱知识产权发展有限公司 化合物
CN110446700A (zh) * 2017-01-25 2019-11-12 葛兰素史密斯克莱知识产权发展有限公司 化合物
WO2019074810A1 (fr) * 2017-10-11 2019-04-18 Merck Sharp & Dohme Corp. Dérivés d'indazolyl-spiro [2,3] hexane-carbonitrile comme inhibiteurs de lrrk2, compositions pharmaceutiques, et utilisations de ceux-ci
WO2019074809A1 (fr) * 2017-10-11 2019-04-18 Merck Sharp & Dohme Corp. Dérivés d'indazolyl-spiro [2.2] pentane-carbonitrile en tant qu'inhibiteurs de lrrk2, compositions pharmaceutiques et leurs utilisations
WO2023283606A1 (fr) * 2021-07-08 2023-01-12 Dana-Farber Cancer Institute, Inc. Agents de dégradation de formes mutantes et de type sauvage de lrrk2 et leurs utilisations

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