CA3229539A1 - Inhibitors of nlrp3 - Google Patents

Inhibitors of nlrp3 Download PDF

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Publication number
CA3229539A1
CA3229539A1 CA3229539A CA3229539A CA3229539A1 CA 3229539 A1 CA3229539 A1 CA 3229539A1 CA 3229539 A CA3229539 A CA 3229539A CA 3229539 A CA3229539 A CA 3229539A CA 3229539 A1 CA3229539 A1 CA 3229539A1
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CA
Canada
Prior art keywords
amino
phenol
trifluoromethyl
triazin
methylpiperidin
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
CA3229539A
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English (en)
French (fr)
Inventor
Xiaoyan Zhang
Rauful Alam
Scott J. Barraza
Lauren BEJCEK
Bradley B. GILBERT
Hua Gong
Handoko -
Seyedmorteza HOSSEYNI
Eduardo HUARTE
Woohyung JEON
Jing Li
Yao Liu
Kyle NIEDERER
Erica N. Parker
Meenu PILLAI
Ettore RASTELLI
Nadiya Sydorenko
Anthony Turpoff
Matthew G. Woll
Nanjing Zhang
Yan Zhang
Tianyi ZHENG
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PTC Therapeutics Inc
Original Assignee
PTC Therapeutics Inc
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Filing date
Publication date
Application filed by PTC Therapeutics Inc filed Critical PTC Therapeutics Inc
Publication of CA3229539A1 publication Critical patent/CA3229539A1/en
Pending legal-status Critical Current

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50Pyridazines; Hydrogenated pyridazines
    • A61K31/502Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50Pyridazines; Hydrogenated pyridazines
    • A61K31/5025Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/53Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535Heterocyclic 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
    • A61K31/53751,4-Oxazines, e.g. morpholine
    • A61K31/53771,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535Heterocyclic 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
    • A61K31/53751,4-Oxazines, e.g. morpholine
    • A61K31/53831,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/553Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/5545Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having eight-membered rings not containing additional condensed or non-condensed nitrogen-containing 3-7 membered rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D237/00Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
    • C07D237/26Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
    • C07D237/30Phthalazines
    • C07D237/34Phthalazines with nitrogen atoms directly attached to carbon atoms of the nitrogen-containing ring, e.g. hydrazine radicals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic 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
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic 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
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic 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
    • C07D471/02Heterocyclic 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
    • C07D471/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic 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
    • C07D487/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
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    • C07D491/00Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04Ortho-condensed systems
    • C07D491/044Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
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    • C07D495/00Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
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    • C07D495/04Ortho-condensed systems
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    • C07D498/00Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02Heterocyclic 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
    • C07D498/04Ortho-condensed systems
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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
CA3229539A 2021-08-25 2022-08-24 Inhibitors of nlrp3 Pending CA3229539A1 (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US202163237049P 2021-08-25 2021-08-25
US63/237,049 2021-08-25
US202263311463P 2022-02-18 2022-02-18
US63/311,463 2022-02-18
PCT/US2022/075421 WO2023028534A1 (en) 2021-08-25 2022-08-24 Inhibitors of nlrp3

Publications (1)

Publication Number Publication Date
CA3229539A1 true CA3229539A1 (en) 2023-03-02

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ID=83438923

Family Applications (1)

Application Number Title Priority Date Filing Date
CA3229539A Pending CA3229539A1 (en) 2021-08-25 2022-08-24 Inhibitors of nlrp3

Country Status (14)

Country Link
US (1) US20240262806A1 (enExample)
EP (1) EP4392414A1 (enExample)
JP (1) JP2024534162A (enExample)
KR (1) KR20240069714A (enExample)
AU (1) AU2022334474A1 (enExample)
CA (1) CA3229539A1 (enExample)
CL (1) CL2024000552A1 (enExample)
CO (1) CO2024001922A2 (enExample)
CR (1) CR20240093A (enExample)
EC (1) ECSP24014832A (enExample)
IL (1) IL310992A (enExample)
MX (1) MX2024002342A (enExample)
PE (1) PE20241727A1 (enExample)
WO (1) WO2023028534A1 (enExample)

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US11618751B1 (en) 2022-03-25 2023-04-04 Ventus Therapeutics U.S., Inc. Pyrido-[3,4-d]pyridazine amine derivatives useful as NLRP3 derivatives
US11319319B1 (en) 2021-04-07 2022-05-03 Ventus Therapeutics U.S., Inc. Compounds for inhibiting NLRP3 and uses thereof
TW202319055A (zh) * 2021-07-21 2023-05-16 日商安斯泰來製藥股份有限公司 縮環噠嗪(pyridazine)化合物
CN118302417A (zh) * 2021-08-25 2024-07-05 Ptc医疗公司 Nlrp3抑制剂
WO2023051761A1 (zh) * 2021-09-30 2023-04-06 成都奥睿药业有限公司 一类取代杂芳酞嗪衍生物的药学用途及其制备方法
WO2023088856A1 (en) 2021-11-17 2023-05-25 F. Hoffmann-La Roche Ag Heterocyclic nlrp3 inhibitors
WO2023178099A1 (en) * 2022-03-15 2023-09-21 Zomagen Biosciences Ltd Nlrp3 modulators
CA3246681A1 (en) * 2022-03-25 2023-09-28 Ventus Therapeutics U.S., Inc. PYRIDO-[3,4-D]PYRIDAZINE AMINE DERIVATIVES USEFUL AS NLRP3 DERIVATIVES
JP2025511199A (ja) * 2022-03-31 2025-04-15 ハンチョウ ハイライトゥル ファーマシューティカル カンパニー リミテッド Nlrp3インフラマソーム阻害剤
US20260015357A1 (en) * 2022-07-01 2026-01-15 Neumora Therapeutics, Inc. Modulators of nlrp3 inflammasome and related products and methods
JP2025524640A (ja) * 2022-07-14 2025-07-30 エーシー・イミューン・エス・アー Nlrp3インフラマソーム経路の調節剤としてのピロロトリアジン及びイミダゾトリアジン誘導体
JP2025023868A (ja) * 2022-09-23 2025-02-17 メルク・シャープ・アンド・ドーム・エルエルシー Nod様受容体タンパク質3の阻害剤として有用なフタラジン誘導体
IL319619A (en) * 2022-09-23 2025-05-01 Merck Sharp & Dohme Llc Phthalazine derivatives used as NOD-LIKE PROTEIN 3 receptor inhibitors
US12331048B2 (en) 2022-10-31 2025-06-17 Ventus Therapeutics U.S., Inc. Pyrido-[3,4-d]pyridazine amine derivatives useful as NLRP3 inhibitors
AU2023371859A1 (en) * 2022-11-04 2025-06-12 Transthera Sciences (Nanjing) , Inc. Nlrp3 inflammasome inhibitor and use thereof
CN120379995A (zh) * 2022-12-27 2025-07-25 正大天晴药业集团股份有限公司 一种哒嗪稠芳环化合物及其用途
KR20250106322A (ko) * 2022-12-28 2025-07-09 장춘 진사이언스 파마슈티컬 씨오., 엘티디. 피리다진계 nlrp3 억제제 화합물, 약학 조성물 및 이의 제조 방법과 용도
JP2026504419A (ja) * 2023-01-31 2026-02-05 ヤンセン ファーマシューティカ エヌ.ベー. Nlrp3阻害剤としての2-(ピリダジン-3-イル)-5-(トリフルオロメチル)フェノール
KR20250134147A (ko) * 2023-01-31 2025-09-09 얀센 파마슈티카 엔브이 NLRP3 억제제로서의 피롤로[1,2-d][1,2,4]트리아진 및 피라졸로[1,5-d] [1,2,4]트리아진
AR132116A1 (es) * 2023-03-14 2025-05-28 Sanofi Sa Compuestos de piridazina, su preparación y sus usos terapéuticos
TW202448892A (zh) * 2023-04-17 2024-12-16 大陸商上海拓界生物醫藥科技有限公司 稠合噠嗪類衍生物及其用途
KR20260027946A (ko) 2023-06-02 2026-03-03 머크 샤프 앤드 돔 엘엘씨 Nod-유사 수용체 단백질 3의 억제제로서 유용한 5,6 불포화 비시클릭 헤테로사이클
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