AU2018302178A1 - 1,8-naphthyridinone compounds and uses thereof - Google Patents
1,8-naphthyridinone compounds and uses thereof Download PDFInfo
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- AU2018302178A1 AU2018302178A1 AU2018302178A AU2018302178A AU2018302178A1 AU 2018302178 A1 AU2018302178 A1 AU 2018302178A1 AU 2018302178 A AU2018302178 A AU 2018302178A AU 2018302178 A AU2018302178 A AU 2018302178A AU 2018302178 A1 AU2018302178 A1 AU 2018302178A1
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- Prior art keywords
- alkylene
- halogen
- compound
- alkyl
- oxo
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- 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.)
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- ZFRUGZMCGCYBRC-UHFFFAOYSA-N 1h-1,8-naphthyridin-2-one Chemical class C1=CC=NC2=NC(O)=CC=C21 ZFRUGZMCGCYBRC-UHFFFAOYSA-N 0.000 title abstract description 3
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- 125000002947 alkylene group Chemical group 0.000 claims description 390
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- 125000005843 halogen group Chemical group 0.000 claims description 129
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- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 claims description 60
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 55
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Classifications
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- 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
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
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- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
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- 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
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- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- 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
Landscapes
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- Organic Chemistry (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
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| KR20200040764A (ko) * | 2017-07-18 | 2020-04-20 | 누베이션 바이오 인크. | 1,8-나프티리디논 화합물 및 그의 용도 |
| CN113613655A (zh) * | 2019-01-18 | 2021-11-05 | 诺维逊生物股份有限公司 | 化合物及其用途 |
| KR20210116550A (ko) | 2019-01-18 | 2021-09-27 | 누베이션 바이오 인크. | 아데노신 길항제로서의 헤테로시클릭 화합물 |
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| CN114507231B (zh) * | 2020-11-17 | 2025-06-03 | 南京再明医药有限公司 | 内酰胺类化合物及其制备方法 |
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| KR101491938B1 (ko) * | 2010-07-14 | 2015-02-10 | 노파르티스 아게 | Ｉｐ 수용체 효능제 헤테로시클릭 화합물 |
| CN103261202B (zh) * | 2010-09-24 | 2016-01-20 | 阿迪维纳斯疗法有限公司 | 作为腺苷受体拮抗剂的稠合三环化合物 |
| EP2718978B1 (en) | 2011-06-09 | 2018-05-16 | Novaled GmbH | Organic electronic device |
| UY34572A (es) | 2012-01-13 | 2013-09-02 | Novartis Ag | Compuestos heterocíclicos agonistas del receptor ip |
| US9266891B2 (en) | 2012-11-16 | 2016-02-23 | Boehringer Ingelheim International Gmbh | Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| JP6401773B2 (ja) | 2013-03-11 | 2018-10-10 | ザ リージェンツ オブ ザ ユニヴァシティ オブ ミシガン | Ｂｅｔブロモドメイン阻害剤およびこれを用いる治療方法 |
| EP3521284B1 (en) | 2013-03-15 | 2020-12-02 | The Trustees of Columbia University in the City of New York | Pyrazine compounds as map kinase modulators and uses thereof |
| SG11201510409QA (en) | 2013-06-21 | 2016-01-28 | Zenith Epigenetics Corp | Novel bicyclic bromodomain inhibitors |
| CN104341386A (zh) | 2013-07-23 | 2015-02-11 | 中国科学院上海药物研究所 | 一类芳基杂环小分子化合物、其衍生物及其制备方法和用途 |
| EP3027616B1 (en) | 2013-07-30 | 2018-01-10 | Boehringer Ingelheim International GmbH | Azaindole compounds as modulators of rorc |
| CN106029076B (zh) | 2013-11-18 | 2019-06-07 | 福马疗法公司 | 作为bet溴域抑制剂的苯并哌嗪组合物 |
| ES2860695T3 (es) | 2013-11-18 | 2021-10-05 | Forma Therapeutics Inc | Composiciones de tetrahidroquinolina como inhibidores de bromodominio BET |
| CA2940554A1 (en) | 2014-02-28 | 2015-09-03 | The Regents Of The University Of Michigan | 9h-pyrimido[4,5-b]indoles and related analogs as bet bromodomain inhibitors |
| DK3674302T3 (da) | 2014-04-23 | 2023-04-03 | Incyte Holdings Corp | 1h-pyrrolo[2,3-c]pyridin-7(6h)-oner og pyrazolo[3,4-c]pyridin-7(6h)-oner som inhibitorer af bet-proteiner |
| ES2706888T3 (es) * | 2014-09-19 | 2019-04-01 | Forma Therapeutics Inc | Referencia cruzada a aplicaciones relacionadas |
| CA2967944C (en) | 2014-11-18 | 2020-11-17 | Merck Sharp & Dohme Corp. | Aminopyrazine compounds with a2a antagonist properties |
| HK1245248B (en) | 2014-12-11 | 2020-05-15 | 恒翼生物医药(上海)股份有限公司 | Substituted heterocycles as bromodomain inhibitors |
| EP3262045A1 (en) | 2015-02-27 | 2018-01-03 | The Regents of The University of Michigan | 9h-pyrimido [4,5-b]indoles as bet bromodomain inhibitors |
| JP2018527293A (ja) | 2015-06-16 | 2018-09-20 | オリオン コーポレーション | ブロモドメイン阻害剤としてのスピロ［シクロブタン−１，３’−インドリン］−２’−オン誘導体 |
| SI3334431T1 (sl) | 2015-08-11 | 2020-01-31 | Novartis Ag | 5-bromo-2,6-di-(1h-pirazol-l-il)pyrimidin-4-amin za uporabo v zdravljenju raka |
| CN106478651B (zh) * | 2015-08-31 | 2019-07-09 | 广东东阳光药业有限公司 | 取代的杂芳基化合物及其组合物和用途 |
| JP6863970B2 (ja) | 2015-09-21 | 2021-04-21 | プレキシコン インコーポレーテッドＰｌｅｘｘｉｋｏｎ Ｉｎｃ． | ヘテロ環式化合物およびそれらの使用 |
| RU2018112312A (ru) | 2015-09-22 | 2019-10-23 | ГлаксоСмитКлайн Интеллекчуал Проперти (N2) Лимитед | Пиридинондикарбоксамиды для применения в качестве ингибиторов бромодомена |
| MX391382B (es) | 2015-12-24 | 2025-03-21 | Corvus Pharmaceuticals Inc | Métodos de tratamiento de cáncer |
| AU2017290748A1 (en) | 2016-07-01 | 2019-01-17 | G1 Therapeutics, Inc. | Pyrimidine-based antiproliferative agents |
| NZ749275A (en) | 2016-07-01 | 2023-06-30 | G1 Therapeutics Inc | Synthesis of n-(heteroaryl)-pyrrolo[2,3-d]pyrimidin-2-amines |
| WO2018005533A1 (en) | 2016-07-01 | 2018-01-04 | G1 Therapeutics, Inc. | Antiproliferative pyrimidine-based compounds |
| GB201612092D0 (en) | 2016-07-12 | 2016-08-24 | Almac Discovery Ltd | Pharmaceutical compounds |
| WO2018081863A1 (en) | 2016-11-04 | 2018-05-11 | University Of Wollongong | 6-SUBSTITUTED DERIVATIVES OF HEXAMETHYLENE AMILORIDE AS INHIBITORS OF uPA AND USES THEREOF |
| HRP20231157T1 (hr) | 2017-01-20 | 2024-01-05 | Arcus Biosciences, Inc. | Azolopirimidin za liječenje poremećaja povezanih s rakom |
| WO2018178338A1 (en) | 2017-03-30 | 2018-10-04 | Iteos Therapeutics | 2-oxo-thiazole derivatives as a2a inhibitors and compounds for use in the treatment of cancers |
| EP4112623A1 (en) | 2017-03-30 | 2023-01-04 | iTeos Belgium SA | 2-oxo-thiazole derivatives as a2a inhibitors and compounds for use in the treatment of cancers |
| CN107221611B (zh) | 2017-06-15 | 2019-02-05 | 江西冠能光电材料有限公司 | 一种稳定易加工有机半导体材料及其有机发光器件应用 |
| WO2019002606A1 (en) | 2017-06-30 | 2019-01-03 | Selvita S.A. | ADENOSINE A2A RECEPTOR 5,6-BICYCLO-IMIDAZO [1,2-A] PYRAZINE MODULATORS |
| WO2019018584A1 (en) | 2017-07-18 | 2019-01-24 | GiraFpharma LLC | HETEROCYCLIC COMPOUNDS AS ADENOSINE ANTAGONISTS |
| KR20200040764A (ko) * | 2017-07-18 | 2020-04-20 | 누베이션 바이오 인크. | 1,8-나프티리디논 화합물 및 그의 용도 |
| JP2021502342A (ja) | 2017-11-06 | 2021-01-28 | コーバス・ファーマシューティカルズ・インコーポレイテッド | 癌処置のためのアデノシン経路阻害剤 |
| CN109810111B (zh) | 2017-11-20 | 2023-10-27 | 上海医药集团股份有限公司 | 一种吡唑酮并嘧啶类化合物、其制备方法及应用 |
| EP3723754A4 (en) | 2017-12-13 | 2021-05-19 | Merck Sharp & Dohme Corp. | IMIDAZO [1,2-C] QUINAZOLINE-5-AMINE COMPOUNDS WITH PROPERTIES OF A2A ANTAGONIST |
| BR112020012527A2 (pt) | 2017-12-20 | 2020-11-24 | Betta Pharmaceuticals Co., Ltd | composto que funciona como inibidor de proteína com bromodomínio, e composição |
| CN111315747B (zh) | 2018-01-05 | 2023-05-02 | 四川科伦博泰生物医药股份有限公司 | 二氢吡唑酮并嘧啶类化合物及其制备方法和用途 |
| US11427593B2 (en) | 2018-01-16 | 2022-08-30 | Shanghai Institute Of Materia Medica, Chinese Academy Of Sciences | Bromodomain inhibitor compound and use thereof |
| WO2019148161A1 (en) | 2018-01-29 | 2019-08-01 | Beta Pharma, Inc. | 2h-indazole derivatives as cdk4 and cdk6 inhibitors and therapeutic uses thereof |
| CN111511745B (zh) | 2018-02-06 | 2022-05-27 | 江苏恒瑞医药股份有限公司 | 吡唑并[1，5-a][1，3，5]三嗪-2-胺类衍生物、其制备方法及其应用 |
| JP2021512962A (ja) | 2018-02-13 | 2021-05-20 | アイオバンス バイオセラピューティクス，インコーポレイテッド | アデノシンａ２ａ受容体アンタゴニストによる腫瘍浸潤性リンパ球（ｔｉｌ）の拡大培養並びにｔｉｌ及びアデノシンａ２ａ受容体アンタゴニストの治療的組み合わせ |
| WO2019158070A1 (zh) | 2018-02-15 | 2019-08-22 | 杭州阿诺生物医药科技有限公司 | A2a和/或a2b受体拮抗剂 |
| US11479555B2 (en) | 2018-02-23 | 2022-10-25 | Newave Pharmaceutical Inc. | Substituted 1,2-dihydro-3H-pyrazolo[3,4-D]pyrimidin-3-ones as inhibitors of WEE-1 kinase |
| PE20211001A1 (es) | 2018-02-27 | 2021-06-01 | Incyte Corp | Imidazopirimidinas y triazolopirimidinas como inhibidores de a2a / a2b |
| AU2019227823B2 (en) | 2018-02-28 | 2024-12-12 | The Regents Of The University Of Colorado, A Body Corporate | WEE1 kinase inhibitors and methods of treating cancer using the same |
| KR102810102B1 (ko) | 2018-03-09 | 2025-05-21 | 리커리엄 아이피 홀딩스, 엘엘씨 | 치환된 1,2-다이하이드로-3H-피라졸로[3,4-d]피리미딘-3-온 |
| US11220510B2 (en) | 2018-04-09 | 2022-01-11 | Incyte Corporation | Pyrrole tricyclic compounds as A2A / A2B inhibitors |
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- 2018-07-18 JP JP2020503017A patent/JP2020527593A/ja active Pending
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- 2018-07-18 AU AU2018302178A patent/AU2018302178A1/en not_active Abandoned
- 2018-07-18 WO PCT/US2018/042776 patent/WO2019018583A1/en not_active Ceased
- 2018-07-18 EP EP18835580.4A patent/EP3654982A4/en not_active Withdrawn
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| US20220220111A1 (en) | 2022-07-14 |
| EP3654982A1 (en) | 2020-05-27 |
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| US10793561B2 (en) | 2020-10-06 |
| US20190023702A1 (en) | 2019-01-24 |
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| IL272055A (en) | 2020-03-31 |
| KR20200040764A (ko) | 2020-04-20 |
| CN111093666A (zh) | 2020-05-01 |
| MX2020000693A (es) | 2020-07-29 |
| EP3654982A4 (en) | 2021-04-14 |
| WO2019018583A1 (en) | 2019-01-24 |
| CA3070073A1 (en) | 2019-01-24 |
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