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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gaba
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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
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P25/00—Drugs for disorders of the nervous system
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    • A—HUMAN NECESSITIES
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    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • 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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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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CL (1) CL2018000914A1 (enExample)
CO (1) CO2018003828A2 (enExample)
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ES (1) ES2825349T3 (enExample)
HU (1) HUE053429T2 (enExample)
IL (1) IL258516A (enExample)
LT (1) LT3341355T (enExample)
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PE (1) PE20190349A1 (enExample)
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Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EA038071B1 (ru) 2014-08-21 2021-07-01 Бёрингер Ингельхайм Интернациональ Гмбх СОЕДИНЕНИЕ СПИРО[3H-ИНДОЛ-3,2'-ПИРРОЛИДИН]-2(1H)-ОНА И ЕГО ПРОИЗВОДНЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ MDM2-p53
EP3341355B1 (en) * 2015-10-09 2020-09-30 Northwestern University (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
MX377009B (es) 2015-10-09 2025-03-07 Boehringer Ingelheim Int Nuevos compuestos de espiro[3h-indol-3,2´-pirrolidin]-2(1h)-ona y derivados como inhibidores de mdm2-p53.
IL268212B2 (en) 2017-02-08 2024-06-01 Ovid Therapeutics Inc Methods for treating seizure disorders and Prader-Willi syndrome
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
JP2021512920A (ja) * 2018-02-08 2021-05-20 オービッド・セラピューティクス・インコーポレイテッドＯｖｉｄ Ｔｈｅｒａｐｅｕｔｉｃｓ Ｉｎｃ． 耳鳴、急性感音性難聴、メニエール病、トゥレット症候群、注意欠陥多動性障害、および嗜癖の治療における（１ｓ，３ｓ）−３−アミノ−４−（ジフルオロメチリデン）シクロペンタン−１−カルボン酸および（ｓ）−３−アミノ−４−（ジフルオロメチルエニル）シクロペンタ−１−エン−１−カルボン酸の使用
EP3758693A4 (en) * 2018-03-29 2021-06-02 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 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
KR20250051780A (ko) * 2018-05-25 2025-04-17 노오쓰웨스턴 유니버시티 (s)-3-아미노-4-(디플루오로메틸레닐)사이클로펜트-1-엔-1-카르복실산의합성을 위한 공정
PL3813816T3 (pl) 2018-06-07 2023-07-31 Ovid Therapeutics Inc. Zastosowanie kwasu (s)-3-amino-4-(difluorometylenylo)cyklopentano-1-eno-1-karboksylowego i związków pokrewnych, kwasu (1s,3s)-3-amino-4-(difluorometylideno)cyklopentano-1-karboksylowego w leczeniu zespołu łamliwego chromosomu x lub zespołu drżenia/ataksji związanego z zespołem łamliwego chromosomu x
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
WO2020206234A1 (en) 2019-04-03 2020-10-08 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
JP2024510422A (ja) * 2021-03-03 2024-03-07 ノースウェスタン ユニバーシティ ヒトオルニチンアミノトランスフェラーゼの選択的不活化剤としての３－アミノ－４，４－ジハロシクロペンタ－１－エンカルボン酸
US20240009160A1 (en) * 2022-07-06 2024-01-11 Ovid Therapeutics, Inc. Use of (s)-3-amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid in the treatment of cancer
WO2024173747A1 (en) * 2023-02-17 2024-08-22 Ovid Therapeutics Inc. Use of (s)-3-amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid in the treatment of diabetes and pre-diabetes
KR20250149771A (ko) * 2023-02-17 2025-10-16 오비드 테라퓨틱스 인크. 위장관 장애의 치료 및 면역조절제로서의 (s)-3-아미노-4-(디플루오로메틸레닐)사이클로펜트-1-엔-1-카르복시산의 용도
CN120659624A (zh) * 2023-02-17 2025-09-16 奥维德医疗公司 (s)-3-氨基-4-(二氟亚甲基)环戊-1-烯-1-甲酸在治疗多发性硬化中的用途
US20240285563A1 (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 rheumatoid arthritis

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
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

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3341355B1 (en) * 2015-10-09 2020-09-30 Northwestern University (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

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
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

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
QSAR analysis of a few GABA aminotransferase inhibitors as potent antiepileptics;LU.H.等;《Indian Journal of Chemistry》;20051231;第44B卷;第595-599页 *
Richard B. Silverman等.Fluorinated Conformationally Restricted ç-Aminobutyric Acid Aminotransferase Inhibitors.《J. Med. Chem.》.2006,第49卷第7404-7412页. *
The effects of cyclopentane and cyclopentene analogues of GABA at recombinant GABA receptors;Mary Chebib等;《European Journal of Pharmacology》;20011231;第430卷;第185-192页 *

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MX380592B (es) 2025-03-12
US20180271816A1 (en) 2018-09-27
BR112018007026A2 (pt) 2018-10-16
WO2017062942A3 (en) 2018-03-01
KR20180052782A (ko) 2018-05-18
CN108137484A (zh) 2018-06-08
EP3341355A4 (en) 2019-04-10
LT3341355T (lt) 2020-11-10
HK1253002A1 (zh) 2019-06-06
BR112018007026B1 (pt) 2022-06-21
IL258516A (en) 2018-05-31
CL2018000914A1 (es) 2018-08-31
JP6841821B2 (ja) 2021-03-10
KR102745965B1 (ko) 2024-12-20
ES2825349T3 (es) 2021-05-17
US20170101364A1 (en) 2017-04-13
CA3001330A1 (en) 2017-04-13
HUE053429T2 (hu) 2021-07-28
PT3341355T (pt) 2020-10-21
EP3341355A2 (en) 2018-07-04
US9993449B2 (en) 2018-06-12
PE20190349A1 (es) 2019-03-07
EP3341355B1 (en) 2020-09-30
DK3341355T3 (da) 2020-10-26
AU2016334396A1 (en) 2018-04-19
WO2017062942A2 (en) 2017-04-13
JP2018531941A (ja) 2018-11-01
US20170239202A1 (en) 2017-08-24
AU2016334396B2 (en) 2021-04-08
PL3341355T3 (pl) 2021-03-08
US9670141B2 (en) 2017-06-06
CO2018003828A2 (es) 2018-07-19
MX2018004302A (es) 2018-11-09

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