CN108137484B - 作为用于治疗癫痫、成瘾和肝细胞癌的gaba氨基转移酶灭活剂的化合物 - Google Patents

作为用于治疗癫痫、成瘾和肝细胞癌的gaba氨基转移酶灭活剂的化合物 Download PDF

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CN108137484B
CN108137484B CN201680059069.9A CN201680059069A CN108137484B CN 108137484 B CN108137484 B CN 108137484B CN 201680059069 A CN201680059069 A CN 201680059069A CN 108137484 B CN108137484 B CN 108137484B
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CN108137484A (zh
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理查德·B·西尔弗曼
高屋健治
候昂·V·勒
乔斯·I·扬科萨
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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
    • A61K31/185—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
    • A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
    • 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
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • 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
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A—HUMAN NECESSITIES
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    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
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    • 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
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    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
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    • C07C229/46—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino or carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
    • C07C229/48—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino or carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups and carboxyl groups bound to carbon atoms of the same non-condensed ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/10—Systems containing only non-condensed rings with a five-membered ring the ring being unsaturated

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  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
CN201680059069.9A 2015-10-09 2016-10-10 作为用于治疗癫痫、成瘾和肝细胞癌的gaba氨基转移酶灭活剂的化合物 Active CN108137484B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201562239330P 2015-10-09 2015-10-09
US62/239,330 2015-10-09
PCT/US2016/056245 WO2017062942A2 (en) 2015-10-09 2016-10-10 (s)-3-amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid, and related compounds as gaba aminotransferase inactivators for the treatment of epilepsy, addiction and hepatocellular carcinoma

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CN108137484A CN108137484A (zh) 2018-06-08
CN108137484B true CN108137484B (zh) 2021-02-12

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US (3) US9670141B2 (enExample)
EP (1) EP3341355B1 (enExample)
JP (1) JP6841821B2 (enExample)
KR (1) KR102745965B1 (enExample)
CN (1) CN108137484B (enExample)
AU (1) AU2016334396B2 (enExample)
BR (1) BR112018007026B1 (enExample)
CL (1) CL2018000914A1 (enExample)
CO (1) CO2018003828A2 (enExample)
DK (1) DK3341355T3 (enExample)
ES (1) ES2825349T3 (enExample)
HU (1) HUE053429T2 (enExample)
IL (1) IL258516A (enExample)
LT (1) LT3341355T (enExample)
MX (1) MX380592B (enExample)
PE (1) PE20190349A1 (enExample)
PL (1) PL3341355T3 (enExample)
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WO (1) WO2017062942A2 (enExample)

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JP6591532B2 (ja) 2014-08-21 2019-10-16 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング ＭＤＭ２−ｐ５３阻害剤としての新しいスピロ［３Ｈ−インドール−３，２’−ピロリジン］−２（１Ｈ）−オン化合物および誘導体
CN108137484B (zh) * 2015-10-09 2021-02-12 西北大学 作为用于治疗癫痫、成瘾和肝细胞癌的gaba氨基转移酶灭活剂的化合物
HUE054985T2 (hu) 2015-10-09 2021-11-29 Boehringer Ingelheim Int Spiro[3H-indol-3,2'-pirrolidin]-2(1H)-on vegyületek és számrazékok, mint MDM2-P53 inhibitorok
KR20240110989A (ko) * 2017-02-08 2024-07-16 오비드 테라퓨틱스 인크. 프라더-윌리 증후군 및 발작 장애들을 치료하는 방법들
US10653652B2 (en) 2018-02-08 2020-05-19 Ovid Therapeutics Inc. Use of (1S,3S)-3-amino-4-(difluoromethylidene) cyclopentane-1-carboxylic acid and (S)-3-amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid in the treatment of tinnitus, acute sensorineural hearing loss, meniere'S disease, tourette'S syndrome, attention deficit hyperactivity disorder and addiction
US11771671B2 (en) 2018-02-08 2023-10-03 Ovid Therapeutics Inc. Use of (1S,3S)-3-amino-4-(difluoromethylidene) cyclopentane-1-carboxylic acid and (S)-3-amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid in the treatment of tinnitus, acute sensorineural hearing loss, Meniere's disease, Tourette's syndrome, attention deficit hyperactivity disorder and addiction
AU2019243586A1 (en) * 2018-03-29 2020-10-15 Ovid Therapeutics Inc. Use of (1S,3S)-3-amino-4-(difluoromethylidene) cyclopentane-1-carboxylic acid and (S)-3-amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid in the treatment of eye disorders
US10822301B2 (en) * 2018-04-12 2020-11-03 Northwestern University 3-carbon substituted 4-aminocyclopent-1-ene-1-carboxylic acid compounds as inhibitors of gamma-aminobutyric acid (GABA) aminotransferase
JP7475055B2 (ja) 2018-05-25 2024-04-26 ノースウェスタン ユニバーシティ （ｓ）－３－アミノ－４－（ジフルオロメチレニル）シクロペンタ－１－エン－１－カルボン酸の合成法
WO2019236938A1 (en) 2018-06-07 2019-12-12 Ovid Therapeutics Inc. Use of (s)-3-amino-4-(difluoromethylenyl) cyclopent-1-ene-1-carboxylic acid and related compounds, (1s,3s)-3-amino-4-(difluoromethylidene) cyclopentane-1-carboxylic acid and vigabatrin in the treatment of developmental disorders
US11203596B2 (en) 2019-02-25 2021-12-21 Northwestern University Analogs of 3-amino-4-(propan-2-ylidene)cyclopentane-1-carboxylic acid and uses thereof for treating diseases and disorders associated with ornithine aminotransferase activity
US11078153B2 (en) 2019-04-03 2021-08-03 Northwestern University 2-difluoro substituted 4-aminocyclopentanecarboxylic acids as inhibitors of gamma-aminobutyric acid aminotransferase and human ornithine aminotransferase
CN110935495B (zh) * 2019-11-29 2021-02-23 中国科学院电子学研究所 Gaba和电生理微纳同步传感检测芯片及其制备方法
US11993569B2 (en) 2020-01-23 2024-05-28 Northwestern University 3-amino-4-halocyclopentene carboxylic acids as inactivators of aminotransferases
EP4301724A4 (en) * 2021-03-03 2025-05-28 Northwestern University (S)-3-AMINO-4,4-DIHALOCYCLOPENT-1-CARBOXYLIC ACID AS SELECTIVE INACTIVATORS OF HUMAN ORNITHINE AMINOTRANSFERASE
US20250171397A1 (en) * 2022-02-27 2025-05-29 Northwestern University (3s,4r)-3-amino-4-(difluoromethyl)cyclopent-1-ene-1-carboxylic acid and related compounds as selective inactivators of ornithine aminotransferase
KR20250034134A (ko) * 2022-07-06 2025-03-10 오비드 테라퓨틱스 인크. 암 치료에 있어서 (s)-3-아미노-4-(디플루오로메틸렌일)사이클로펜트-1-엔-1-카르복실산의 사용
KR20250145687A (ko) * 2023-02-17 2025-10-13 오비드 테라퓨틱스 인크. 류마티스 관절염의 치료에 있어서 (s)-3-아미노-4-(디플루오로메틸레닐)사이클로펜트-1-엔-1-카르복시산의 용도
US20240285565A1 (en) 2023-02-17 2024-08-29 Ovid Therapeutics Inc. Use of (s)-3-amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid in the treatment of diabetes and pre-diabetes
AU2024220869A1 (en) 2023-02-17 2025-09-04 Ovid Therapeutics Inc. Use of (s)-3-amino-4-(difluoromethylenyl) cyclopent-1-ene-1-carboxylic acid in the treatment of multiple sclerosis
IL322802A (en) 2023-02-17 2025-10-01 Ovid Therapeutics Inc Use of (s)-3-amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid in the treatment of gastrointestinal disorders and as an immunomodulatory agent

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WO2008023364A1 (en) * 2006-08-21 2008-02-28 Hadasit Medical Research Services & Development Ltd. Inhibition of ornithine aminotransferase for the treatment of proliferative disorders
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CN103764640A (zh) * 2011-08-30 2014-04-30 吉利德科学股份有限公司 成瘾治疗中的aldh-2抑制剂

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US6794413B1 (en) * 2002-07-19 2004-09-21 Northwestern University Compounds and related methods for inhibition of γ-aminobutyric acid aminotransferase
WO2008023364A1 (en) * 2006-08-21 2008-02-28 Hadasit Medical Research Services & Development Ltd. Inhibition of ornithine aminotransferase for the treatment of proliferative disorders
WO2011106692A2 (en) * 2010-02-25 2011-09-01 Northwestern University Methods of using (1s, 3s) -3-amino-4-difluoromethylenyl-1-cyclopentanoic acid
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DK3341355T3 (da) 2020-10-26
IL258516A (en) 2018-05-31
EP3341355A4 (en) 2019-04-10
KR20180052782A (ko) 2018-05-18
HK1253002A1 (zh) 2019-06-06
MX2018004302A (es) 2018-11-09
ES2825349T3 (es) 2021-05-17
BR112018007026B1 (pt) 2022-06-21
AU2016334396A1 (en) 2018-04-19
US20180271816A1 (en) 2018-09-27
US9993449B2 (en) 2018-06-12
HUE053429T2 (hu) 2021-07-28
PT3341355T (pt) 2020-10-21
US20170101364A1 (en) 2017-04-13
CO2018003828A2 (es) 2018-07-19
CA3001330A1 (en) 2017-04-13
PE20190349A1 (es) 2019-03-07
WO2017062942A3 (en) 2018-03-01
KR102745965B1 (ko) 2024-12-20
US9670141B2 (en) 2017-06-06
MX380592B (es) 2025-03-12
EP3341355A2 (en) 2018-07-04
LT3341355T (lt) 2020-11-10
JP2018531941A (ja) 2018-11-01
BR112018007026A2 (pt) 2018-10-16
CN108137484A (zh) 2018-06-08
AU2016334396B2 (en) 2021-04-08
PL3341355T3 (pl) 2021-03-08
CL2018000914A1 (es) 2018-08-31
EP3341355B1 (en) 2020-09-30
WO2017062942A2 (en) 2017-04-13
US20170239202A1 (en) 2017-08-24
JP6841821B2 (ja) 2021-03-10

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