CN113348018B - 乙酰基-亮氨酸的氘代类似物 - Google Patents

乙酰基-亮氨酸的氘代类似物 Download PDF

Info

Publication number
CN113348018B
CN113348018B CN201980090399.8A CN201980090399A CN113348018B CN 113348018 B CN113348018 B CN 113348018B CN 201980090399 A CN201980090399 A CN 201980090399A CN 113348018 B CN113348018 B CN 113348018B
Authority
CN
China
Prior art keywords
present disclosure
compound
subject
disease
leucine
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.)
Active
Application number
CN201980090399.8A
Other languages
English (en)
Chinese (zh)
Other versions
CN113348018A (zh
Inventor
M·曼恩
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.)
Intrabio Ltd
Original Assignee
Intrabio 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 Intrabio Ltd filed Critical Intrabio Ltd
Priority to CN202510303881.2A priority Critical patent/CN120157593A/zh
Publication of CN113348018A publication Critical patent/CN113348018A/zh
Application granted granted Critical
Publication of CN113348018B publication Critical patent/CN113348018B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/45—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
    • C07C233/46—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
    • C07C233/47—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
    • A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
    • A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
    • 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
    • A61P25/06—Antimigraine agents
    • 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
    • A61P25/28—Drugs 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
    • C07B59/001—Acyclic or carbocyclic compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/05—Isotopically modified compounds, e.g. labelled
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Hospice & Palliative Care (AREA)
  • Epidemiology (AREA)
  • Psychiatry (AREA)
  • Pain & Pain Management (AREA)
  • Otolaryngology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
CN201980090399.8A 2018-12-06 2019-12-06 乙酰基-亮氨酸的氘代类似物 Active CN113348018B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202510303881.2A CN120157593A (zh) 2018-12-06 2019-12-06 乙酰基-亮氨酸的氘代类似物

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201862776297P 2018-12-06 2018-12-06
US62/776,297 2018-12-06
PCT/IB2019/060525 WO2020115715A1 (en) 2018-12-06 2019-12-06 Deuterated analogs of acetyl-leucine

Related Child Applications (1)

Application Number Title Priority Date Filing Date
CN202510303881.2A Division CN120157593A (zh) 2018-12-06 2019-12-06 乙酰基-亮氨酸的氘代类似物

Publications (2)

Publication Number Publication Date
CN113348018A CN113348018A (zh) 2021-09-03
CN113348018B true CN113348018B (zh) 2025-04-01

Family

ID=68887086

Family Applications (2)

Application Number Title Priority Date Filing Date
CN201980090399.8A Active CN113348018B (zh) 2018-12-06 2019-12-06 乙酰基-亮氨酸的氘代类似物
CN202510303881.2A Pending CN120157593A (zh) 2018-12-06 2019-12-06 乙酰基-亮氨酸的氘代类似物

Family Applications After (1)

Application Number Title Priority Date Filing Date
CN202510303881.2A Pending CN120157593A (zh) 2018-12-06 2019-12-06 乙酰基-亮氨酸的氘代类似物

Country Status (13)

Country Link
US (2) US12145899B2 (enExample)
EP (1) EP3886986A1 (enExample)
JP (3) JP7471298B2 (enExample)
KR (2) KR102765448B1 (enExample)
CN (2) CN113348018B (enExample)
AU (1) AU2019391434B2 (enExample)
BR (1) BR112021010923A2 (enExample)
IL (2) IL319687A (enExample)
MA (1) MA54289A (enExample)
MX (2) MX2021006559A (enExample)
SA (1) SA521422185B1 (enExample)
SG (1) SG11202106009TA (enExample)
WO (1) WO2020115715A1 (enExample)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB201709459D0 (en) 2017-06-14 2017-07-26 Intrabio Ltd Treatment for migraine
EP3886986A1 (en) 2018-12-06 2021-10-06 IntraBio Ltd Deuterated analogs of acetyl-leucine
WO2022264037A1 (en) * 2021-06-14 2022-12-22 Intrabio Ltd. Branched-chain amino acid derivatives to treat disease
US12403111B2 (en) 2024-02-02 2025-09-02 SynGAP Research Fund Compositions and methods for treating neurodevelopmental disorders

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018029658A1 (en) * 2016-08-11 2018-02-15 Intrabio Limited Therapeutic agents for neurodegenerative diseases

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2293638T3 (es) * 1994-03-25 2008-03-16 Isotechnika, Inc. Mejora de la eficacia de farmacos por deuteracion.
US20060063827A1 (en) 2004-09-23 2006-03-23 Yu Ruey J Systemic administration of therapeutic amino acids and N-acetylamino acids
US20050026823A1 (en) * 2003-06-20 2005-02-03 Biomarin Pharmaceutical Inc. Use of the chaperone receptor-associated protein (RAP) for the delivery of therapeutic compounds to the brain and other tissues
US20120101168A1 (en) * 2010-10-26 2012-04-26 Eliezer Bahar Deuterium enriched rasagiline
ES2901752T3 (es) 2013-02-05 2022-03-23 Teva Pharmaceuticals Int Gmbh Derivados de catecolamina enriquecidos con deuterio asimétrico de posición específica y medicamentos que comprenden dichos compuestos
ES2994242T3 (en) * 2016-04-19 2025-02-05 Intrabio Ltd Acetyl-leucine or a pharmaceutically acceptable salt thereof for improved mobility
DK3359146T3 (en) * 2016-08-11 2019-04-08 Intrabio Ltd PHARMACEUTICAL COMPOSITIONS AND USES AGAINST LYSOSOMAL STORAGE DISEASES
HUE062729T2 (hu) 2017-03-28 2023-12-28 Intrabio Ltd Betahisztin, vagy gyógyászatilag elfogadható sója, és egy monoamin-oxidáz inhibitor, egy alanyban szédülés egy vagy több tünete kezelésében vagy megelõzésében történõ alkalmazásra
GB201709459D0 (en) 2017-06-14 2017-07-26 Intrabio Ltd Treatment for migraine
US12458614B2 (en) 2017-10-18 2025-11-04 Intrabio Ltd Therapeutic agents for improved mobility and cognitive function and for treating neurodegenerative diseases and lysosomal storage disorders
MA51836B1 (fr) 2018-02-15 2025-01-31 Intrabio Ltd Agents thérapeutiques permettant de traiter le syndrome des jambes sans repos
EP3886986A1 (en) 2018-12-06 2021-10-06 IntraBio Ltd Deuterated analogs of acetyl-leucine
US10950670B2 (en) * 2018-12-17 2021-03-16 Wuhan China Star Optoelectronics Semiconductor Display Technology Co., Ltd. Display panel
SMT202400334T1 (it) * 2019-03-02 2024-09-16 Intrabio Ltd (n-)acetil-l-leucina per il trattamento di lesioni cerebrali traumatiche
RS67283B1 (sr) 2019-06-28 2025-11-28 Intrabio Ltd Kombinovana terapija sa acetil-leucinom i miglustatom za lečenje bolesti lizozomskog skladištenja
WO2021144720A1 (en) * 2020-01-13 2021-07-22 Intrabio Ltd Treatment of late-onset neurodegenerative diseases in heterozygous npc1 gene mutation carriers
US20230201150A1 (en) * 2020-05-22 2023-06-29 Intrabio Ltd. The combination of acetyl leucine and 4-aminopyridine or acetazolamide for treating ataxia

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018029658A1 (en) * 2016-08-11 2018-02-15 Intrabio Limited Therapeutic agents for neurodegenerative diseases

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
C. Cardellicchio等.synthesis of u-amino acid derivatives by copper(i)-catalyzed conjugate addition of grignard reagents to methyl 2-acetamidoacrylate.《Tetrahedron Letters》.1985,第26卷(第36期),4389. *
Differential isotope-labeling for Leu and Val residues in a protein by E. coli cellular expression using stereo-specifically methyl labeled amino acids;Yohei Miyanoiri等;《J Biomol NMR》;20130921;第57卷(第3期);第240页Scheme1 *
RICHARD K. HILL.Synthesis of (2S,4S)-and ( 2S , 4R)-[5,5,5-2H3] leucine from (R) pulegone.《Canadian journal of chemistry》.1994,第72卷(第1期),第111页Scheme 2. *
RICHARD K. HILL等.Synthesis of (2S,4S)-and ( 2S , 4R)-[5,5,5-2H3] leucine from (R) pulegone.《Canadian journal of chemistry》.1994,第72卷(第1期),第111页Scheme 2. *
synthesis of u-amino acid derivatives by copper(i)-catalyzed conjugate addition of grignard reagents to methyl 2-acetamidoacrylate;C. Cardellicchio等;《Tetrahedron Letters》;19851231;第26卷(第36期);4389 *
Yohei Miyanoiri等.Differential isotope-labeling for Leu and Val residues in a protein by E. coli cellular expression using stereo-specifically methyl labeled amino acids.《J Biomol NMR》.2013,第57卷(第3期),第240页Scheme1. *

Also Published As

Publication number Publication date
IL283673B1 (en) 2025-04-01
BR112021010923A2 (pt) 2021-08-24
JP7471298B2 (ja) 2024-04-19
KR102765448B1 (ko) 2025-02-07
EP3886986A1 (en) 2021-10-06
CN120157593A (zh) 2025-06-17
IL283673B2 (en) 2025-08-01
KR20250022899A (ko) 2025-02-17
JP2022514823A (ja) 2022-02-16
JP2026016521A (ja) 2026-02-03
AU2019391434B2 (en) 2025-01-09
WO2020115715A1 (en) 2020-06-11
JP2024095769A (ja) 2024-07-10
US12145899B2 (en) 2024-11-19
AU2019391434A1 (en) 2021-07-08
US20250129011A1 (en) 2025-04-24
IL319687A (en) 2025-05-01
US20220024858A1 (en) 2022-01-27
MA54289A (fr) 2021-10-06
CA3122223A1 (en) 2020-06-11
KR20210111757A (ko) 2021-09-13
SG11202106009TA (en) 2021-07-29
MX2024005670A (es) 2024-05-30
SA521422185B1 (ar) 2024-04-24
CN113348018A (zh) 2021-09-03
IL283673A (en) 2021-07-29
MX2021006559A (es) 2021-08-16

Similar Documents

Publication Publication Date Title
CN113348018B (zh) 乙酰基-亮氨酸的氘代类似物
JP5303458B2 (ja) β−グルコセレブロシダーゼの活性増強による神経学的疾患の治療方法
JP6320931B2 (ja) リソソーム酵素を再構成する能力を有する化合物ならびにアンブロキソールおよび／またはアンブロキソールの誘導体の組み合わせ
SG178000A1 (en) Methods and combination therapies for treating alzheimer's disease
TW202337456A (zh) Ｇｍ２神經節苷脂症之治療
EP3989962B1 (en) Combination therapy with acetyl-leucine and miglustat for treating a lysosomal storage disease
US20260108494A1 (en) Therapeutic agent for non-motor symptoms associated with parkinson's disease
CA3122223C (en) Deuterated analogs of acetyl-leucine
RU2810793C2 (ru) Дейтерированные аналоги ацетиллейцина
US20240208895A1 (en) Branched-chain amino acid derivatives to treat disease
TW383337B (en) Process of making (2S,5S)-5-fluoromethylornithine
HK40127928A (en) Combination therapy with acetyl-leucine and miglustat for treating a lysosomal storage disease
US7932287B2 (en) Therapeutic compositions and uses
HK40017297A (en) Therapeutic agent for non-motor symptoms associated with parkinson's disease
HK1168005B (en) Methods for preventing and/or treating degenerative disorders of the central nervous system

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant