AU2021234134B2 - Fused pyrimidine compounds as KCC2 modulators - Google Patents

Fused pyrimidine compounds as KCC2 modulators

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Publication number
AU2021234134B2
AU2021234134B2 AU2021234134A AU2021234134A AU2021234134B2 AU 2021234134 B2 AU2021234134 B2 AU 2021234134B2 AU 2021234134 A AU2021234134 A AU 2021234134A AU 2021234134 A AU2021234134 A AU 2021234134A AU 2021234134 B2 AU2021234134 B2 AU 2021234134B2
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AU
Australia
Prior art keywords
pyrimidin
dihydro
amino
propan
pyrrolo
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AU2021234134A
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English (en)
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AU2021234134A1 (en
Inventor
Roland Werner Bürli
Rebecca Elizabeth Jarvis
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AstraZeneca AB
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AstraZeneca AB
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Publication of AU2021234134A1 publication Critical patent/AU2021234134A1/en
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    • 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
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • 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
    • A61K31/54Heterocyclic 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
    • A61K31/541Non-condensed thiazines containing further heterocyclic rings
    • 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
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/08Antiepileptics; Anticonvulsants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/22Anxiolytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • CCHEMISTRY; METALLURGY
    • 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
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • 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
    • C07D491/048Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • 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
    • C07D498/10Spiro-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D519/00Heterocyclic 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)
AU2021234134A 2020-03-13 2021-03-12 Fused pyrimidine compounds as KCC2 modulators Active AU2021234134B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US202062989104P 2020-03-13 2020-03-13
US62/989,104 2020-03-13
PCT/EP2021/056393 WO2021180952A1 (en) 2020-03-13 2021-03-12 Fused pyrimidine compounds as kcc2

Publications (2)

Publication Number Publication Date
AU2021234134A1 AU2021234134A1 (en) 2022-11-03
AU2021234134B2 true AU2021234134B2 (en) 2025-08-21

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AU2021234134A Active AU2021234134B2 (en) 2020-03-13 2021-03-12 Fused pyrimidine compounds as KCC2 modulators

Country Status (25)

Country Link
US (1) US20230151013A1 (https=)
EP (1) EP4103566B1 (https=)
JP (2) JP7793529B2 (https=)
KR (1) KR20220152319A (https=)
CN (4) CN119735594A (https=)
AU (1) AU2021234134B2 (https=)
BR (1) BR112022018173A2 (https=)
CA (1) CA3171192A1 (https=)
CL (1) CL2022002386A1 (https=)
CO (1) CO2022012884A2 (https=)
DK (1) DK4103566T3 (https=)
ES (1) ES2962136T3 (https=)
FI (1) FI4103566T3 (https=)
HR (1) HRP20231314T1 (https=)
HU (1) HUE064037T2 (https=)
IL (1) IL296265B2 (https=)
LT (1) LT4103566T (https=)
MX (1) MX2022011354A (https=)
PE (1) PE20230106A1 (https=)
PL (1) PL4103566T3 (https=)
PT (1) PT4103566T (https=)
RS (1) RS64823B1 (https=)
SI (1) SI4103566T1 (https=)
SM (1) SMT202300384T1 (https=)
WO (1) WO2021180952A1 (https=)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20240132285A (ko) * 2021-12-08 2024-09-03 키네타, 인크. 비시클릭 헤테로아렌 및 그의 사용 방법
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
CN121548571A (zh) * 2023-04-05 2026-02-17 艾索尼斯治疗公司 Kcc2增强剂及其用途
WO2025188976A1 (en) * 2024-03-06 2025-09-12 Ovid Therapeutics Inc. Fused amino pyrimidine compounds for treatment of neurodegenerative disorders
WO2025188977A1 (en) * 2024-03-06 2025-09-12 Ovid Therapeutics Inc. Fused amino pyrimidine compounds for treatment of addiction and insomnia
US20260048062A1 (en) * 2024-03-06 2026-02-19 Ovid Therapeutics Inc. Fused amino pyrimidine compounds for treatment of psychosis and psychotic disorders
WO2025188974A1 (en) * 2024-03-06 2025-09-12 Ovid Therapeutics Inc. Fused amino pyrimidine compounds for treatment of autism spectrum disorder, obsessive compulsive disorder and tics
WO2025188951A1 (en) * 2024-03-06 2025-09-12 Ovid Therapeutics Inc. Fused amino pyrimidine compounds for treatment of seizure disorders
WO2025188973A1 (en) * 2024-03-06 2025-09-12 Ovid Therapeutics Inc. Fused amino pyrimidine compounds for treatment of 22q11.2 deletion/duplication syndromes
WO2025188953A1 (en) * 2024-03-06 2025-09-12 Ovid Therapeutics Inc. Fused amino pyrimidine compounds for treatment of neuropathic and neuro-inflammatory pain
US20250281500A1 (en) * 2024-03-06 2025-09-11 Ovid Therapeutics Inc. Fused amino pyrimidine compounds and pridopidine for treatment of huntington’s disease
US20250281498A1 (en) * 2024-03-06 2025-09-11 Ovid Therapeutics Inc. Fused amino pyrimidine compounds for treatment of synucleinopathies and tdp-43 proteinopathies

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008136756A1 (en) * 2007-05-08 2008-11-13 Astrazeneca Ab Pyrrolopyrimidin-7-one derivatives and their use as pharmaceuticals
WO2019045824A1 (en) * 2017-09-01 2019-03-07 Kadmon Corporation, Llc ALPHA PROPELLER PROTEIN KINASE INHIBITORS ("COILED-COIL") ASSOCIATED WITH RHO

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015131080A1 (en) * 2014-02-28 2015-09-03 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
KR20210050493A (ko) * 2018-05-25 2021-05-07 더 칠드런스 메디칼 센터 코포레이션 척수 손상의 치료 방법

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008136756A1 (en) * 2007-05-08 2008-11-13 Astrazeneca Ab Pyrrolopyrimidin-7-one derivatives and their use as pharmaceuticals
WO2019045824A1 (en) * 2017-09-01 2019-03-07 Kadmon Corporation, Llc ALPHA PROPELLER PROTEIN KINASE INHIBITORS ("COILED-COIL") ASSOCIATED WITH RHO

Also Published As

Publication number Publication date
CN119735594A (zh) 2025-04-01
CN115298182B (zh) 2025-02-11
EP4103566B1 (en) 2023-10-04
JP7793529B2 (ja) 2026-01-05
PT4103566T (pt) 2023-11-09
IL296265A (en) 2022-11-01
JP2023517680A (ja) 2023-04-26
HRP20231314T1 (hr) 2024-02-16
DK4103566T3 (da) 2023-10-30
AU2021234134A1 (en) 2022-11-03
EP4103566A1 (en) 2022-12-21
CN119684300A (zh) 2025-03-25
JP2025186368A (ja) 2025-12-23
BR112022018173A2 (pt) 2022-10-25
PL4103566T3 (pl) 2024-02-05
SMT202300384T1 (it) 2024-01-10
CL2022002386A1 (es) 2023-04-28
ES2962136T3 (es) 2024-03-15
CO2022012884A2 (es) 2022-10-11
IL296265B1 (en) 2025-12-01
FI4103566T3 (fi) 2023-10-20
US20230151013A1 (en) 2023-05-18
WO2021180952A1 (en) 2021-09-16
RS64823B1 (sr) 2023-12-29
LT4103566T (lt) 2023-11-10
SI4103566T1 (sl) 2024-04-30
CN119684299A (zh) 2025-03-25
IL296265B2 (en) 2026-04-01
PE20230106A1 (es) 2023-01-25
MX2022011354A (es) 2022-11-30
CA3171192A1 (en) 2021-09-16
KR20220152319A (ko) 2022-11-15
CN115298182A (zh) 2022-11-04
HUE064037T2 (hu) 2024-03-28
WO2021180952A9 (en) 2021-12-16

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