CN119684299A - 作为kcc2调节剂的稠合的嘧啶化合物 - Google Patents

作为kcc2调节剂的稠合的嘧啶化合物 Download PDF

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Publication number
CN119684299A
CN119684299A CN202411881248.3A CN202411881248A CN119684299A CN 119684299 A CN119684299 A CN 119684299A CN 202411881248 A CN202411881248 A CN 202411881248A CN 119684299 A CN119684299 A CN 119684299A
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CN
China
Prior art keywords
alkyl
dihydro
optionally substituted
pyrimidin
pyrrolo
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Pending
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CN202411881248.3A
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English (en)
Chinese (zh)
Inventor
R·伊丽莎白·雅维斯
R·维尔纳·比尔利
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AstraZeneca AB
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AstraZeneca AB
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Publication of CN119684299A publication Critical patent/CN119684299A/zh
Pending legal-status Critical Current

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    • 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
    • A61K31/495—Heterocyclic 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with 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
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • 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
    • A61K31/541—Non-condensed thiazines 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/553—Heterocyclic 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
    • 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
    • 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
    • A61P25/08—Antiepileptics; Anticonvulsants
    • 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
    • A61P25/22—Anxiolytics
    • 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]
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic 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
    • C07D491/02—Heterocyclic 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
    • C07D491/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic 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
    • C07D491/02—Heterocyclic 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
    • C07D491/04—Ortho-condensed systems
    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
    • 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
    • C07D498/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
CN202411881248.3A 2020-03-13 2021-03-12 作为kcc2调节剂的稠合的嘧啶化合物 Pending CN119684299A (zh)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US202062989104P 2020-03-13 2020-03-13
US62/989,104 2020-03-13
CN202180020856.3A CN115298182B (zh) 2020-03-13 2021-03-12 作为kcc2调节剂的稠合的嘧啶化合物
PCT/EP2021/056393 WO2021180952A1 (en) 2020-03-13 2021-03-12 Fused pyrimidine compounds as kcc2

Related Parent Applications (1)

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CN202180020856.3A Division CN115298182B (zh) 2020-03-13 2021-03-12 作为kcc2调节剂的稠合的嘧啶化合物

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CN119684299A true CN119684299A (zh) 2025-03-25

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CN202411881248.3A Pending CN119684299A (zh) 2020-03-13 2021-03-12 作为kcc2调节剂的稠合的嘧啶化合物
CN202411881483.0A Pending CN119735594A (zh) 2020-03-13 2021-03-12 作为kcc2调节剂的稠合的嘧啶化合物
CN202180020856.3A Active CN115298182B (zh) 2020-03-13 2021-03-12 作为kcc2调节剂的稠合的嘧啶化合物
CN202411881526.5A Pending CN119684300A (zh) 2020-03-13 2021-03-12 作为kcc2调节剂的稠合的嘧啶化合物

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CN202411881483.0A Pending CN119735594A (zh) 2020-03-13 2021-03-12 作为kcc2调节剂的稠合的嘧啶化合物
CN202180020856.3A Active CN115298182B (zh) 2020-03-13 2021-03-12 作为kcc2调节剂的稠合的嘧啶化合物
CN202411881526.5A Pending CN119684300A (zh) 2020-03-13 2021-03-12 作为kcc2调节剂的稠合的嘧啶化合物

Country Status (25)

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EP (1) EP4103566B1 (cg-RX-API-DMAC7.html)
JP (2) JP7793529B2 (cg-RX-API-DMAC7.html)
KR (1) KR20220152319A (cg-RX-API-DMAC7.html)
CN (4) CN119684299A (cg-RX-API-DMAC7.html)
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Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2022407047A1 (en) * 2021-12-08 2024-07-25 Kineta, Inc. Bicyclic heteroarenes and methods of their use
CN117843618A (zh) * 2022-08-29 2024-04-09 北京沐华生物科技有限责任公司 一种ep300/cbp调节剂及其制备方法和用途
CN121241048A (zh) * 2023-04-05 2025-12-30 艾索尼斯治疗公司 Kcc2增强剂及其用途
US20260191874A1 (en) * 2024-03-06 2026-07-09 Ovid Therapeutics Inc. Fused amino pyrimidine compounds for treatment of autism spectrum disorder, obsessive compulsive disorder and tics
WO2025188955A1 (en) * 2024-03-06 2025-09-12 Ovid Therapeutics Inc. Fused amino pyrimidine compounds for treatment of psychosis and psychotic disorders
WO2025188977A1 (en) * 2024-03-06 2025-09-12 Ovid Therapeutics Inc. Fused amino pyrimidine compounds for treatment of addiction and insomnia
WO2025188976A1 (en) * 2024-03-06 2025-09-12 Ovid Therapeutics Inc. Fused amino pyrimidine compounds for treatment of neurodegenerative disorders
US20250281498A1 (en) * 2024-03-06 2025-09-11 Ovid Therapeutics Inc. Fused amino pyrimidine compounds for treatment of synucleinopathies and tdp-43 proteinopathies
WO2025188973A1 (en) * 2024-03-06 2025-09-12 Ovid Therapeutics Inc. Fused amino pyrimidine compounds for treatment of 22q11.2 deletion/duplication syndromes
WO2025188951A1 (en) * 2024-03-06 2025-09-12 Ovid Therapeutics Inc. Fused amino pyrimidine compounds for treatment of seizure disorders
WO2025188953A1 (en) * 2024-03-06 2025-09-12 Ovid Therapeutics Inc. Fused amino pyrimidine compounds for treatment of neuropathic and neuro-inflammatory pain
WO2025188979A1 (en) * 2024-03-06 2025-09-12 Ovid Therapeutics Inc. Fused amino pyrimidine compounds and pridopidine for treatment of huntington's disease
US20260108529A1 (en) * 2024-10-23 2026-04-23 Ovid Therapeutics Inc. Fused amino pyrimidine compounds for treatment of tinnitus, acute sensorineural hearing loss, age-related hearing loss, and meniere's disease

Family Cites Families (8)

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Publication number Priority date Publication date Assignee Title
JP3398152B2 (ja) 1993-10-12 2003-04-21 ブリストル‐マイヤーズ・スクイブ・ファーマ・カンパニー 1n−アルキル−n−アリールピリミジンアミンおよびその誘導体
US20090099195A1 (en) * 2007-05-08 2009-04-16 Astrazeneca Ab Therapeutic Compounds 570
RS53382B (sr) 2008-08-20 2014-10-31 Zoetis Llc Jedinjenja pirol [2,3-d]pirimidina
AR079814A1 (es) * 2009-12-31 2012-02-22 Otsuka Pharma Co Ltd Compuestos heterociclicos, composiciones farmaceuticas que los contienen y sus usos
US9340540B2 (en) 2014-02-28 2016-05-17 Nimbus Lakshmi, Inc. TYK2 inhibitors and uses thereof
WO2018217766A1 (en) 2017-05-22 2018-11-29 Whitehead Institute For Biomedical Research Kcc2 expression enhancing compounds and uses thereof
JP7399848B2 (ja) * 2017-09-01 2023-12-18 カドモン コーポレイション,リミティド ライアビリティ カンパニー Rho関連コイルドコイル含有プロテインキナーゼの阻害剤
KR20210050493A (ko) * 2018-05-25 2021-05-07 더 칠드런스 메디칼 센터 코포레이션 척수 손상의 치료 방법

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SMT202300384T1 (it) 2024-01-10
CN119735594A (zh) 2025-04-01
EP4103566A1 (en) 2022-12-21
PL4103566T3 (pl) 2024-02-05
JP2023517680A (ja) 2023-04-26
AU2021234134A1 (en) 2022-11-03
JP2025186368A (ja) 2025-12-23
FI4103566T3 (fi) 2023-10-20
PT4103566T (pt) 2023-11-09
HRP20231314T1 (hr) 2024-02-16
IL296265B1 (en) 2025-12-01
LT4103566T (lt) 2023-11-10
ES2962136T3 (es) 2024-03-15
BR112022018173A2 (pt) 2022-10-25
MX2022011354A (es) 2022-11-30
IL296265B2 (en) 2026-04-01
JP7793529B2 (ja) 2026-01-05
DK4103566T3 (da) 2023-10-30
US12617795B2 (en) 2026-05-05
AU2021234134B2 (en) 2025-08-21
CA3171192A1 (en) 2021-09-16
HUE064037T2 (hu) 2024-03-28
WO2021180952A9 (en) 2021-12-16
PE20230106A1 (es) 2023-01-25
SI4103566T1 (sl) 2024-04-30
CN115298182A (zh) 2022-11-04
RS64823B1 (sr) 2023-12-29
WO2021180952A1 (en) 2021-09-16
EP4103566B1 (en) 2023-10-04
IL296265A (en) 2022-11-01
CN115298182B (zh) 2025-02-11
KR20220152319A (ko) 2022-11-15
CL2022002386A1 (es) 2023-04-28
US20230151013A1 (en) 2023-05-18
CO2022012884A2 (es) 2022-10-11
CN119684300A (zh) 2025-03-25

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