KR20170058921A - 신규의 5,6-디하이드로-4H-벤조[b]티에노-[2,3-d]아제핀 유도체 - Google Patents

신규의 5,6-디하이드로-4H-벤조[b]티에노-[2,3-d]아제핀 유도체 Download PDF

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Publication number: KR20170058921A
Authority: KR; South Korea
Prior art keywords: compound; rsv; formula; infection; compounds
Prior art date: 2014-10-10
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 Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Withdrawn

Application number

KR1020177006394A

Other languages

English (en)

Korean (ko)

Inventor

시몬 프레이저 헌트

스튜어트 토마스 어니언스

블라디미르 쉐르부킨

유안 알렉산더 프레이저 포다이스

피터 존 머레이

다니엘 윌리엄 브룩스

카즈히로 이토

피터 스트롱

Original Assignee

풀모사이드 리미티드

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.)

2014-10-10

Filing date

2015-10-08

Publication date

2017-05-29

2015-10-08 Application filed by 풀모사이드 리미티드 filed Critical 풀모사이드 리미티드

2017-05-29 Publication of KR20170058921A publication Critical patent/KR20170058921A/ko

Status Withdrawn legal-status Critical Current

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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
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- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic 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
- C07D491/02—Heterocyclic 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
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic 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
- C07D491/02—Heterocyclic 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
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
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Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Medicinal Preparation (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

KR1020177006394A 2014-10-10 2015-10-08 신규의 5,6-디하이드로-4H-벤조[b]티에노-[2,3-d]아제핀 유도체 Withdrawn KR20170058921A (ko)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
EP14188494.0		2014-10-10
EP14188494		2014-10-10
PCT/GB2015/052944 WO2016055791A1 (en)	2014-10-10	2015-10-08	Novel 5,6-dihydro-4H-benzo[b]thieno-[2,3-d]azepine derivative

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Publication Number	Publication Date
KR20170058921A true KR20170058921A (ko)	2017-05-29

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US (6)	US10189863B2 (2)
EP (2)	EP3204388B1 (2)
JP (2)	JP6675407B2 (2)
KR (1)	KR20170058921A (2)
CN (1)	CN106852144B (2)
AU (1)	AU2015329789B2 (2)
BR (1)	BR112017005104B1 (2)
CA (1)	CA2957868C (2)
EA (1)	EA201790796A8 (2)
IL (1)	IL250823A0 (2)
MX (1)	MX2017004652A (2)
SG (1)	SG11201701184WA (2)
WO (2)	WO2016055791A1 (2)

Families Citing this family (26)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP6675407B2 (ja)	2014-10-10	2020-04-01	プルモシデリミテド	新規５，６−ジヒドロ−４Ｈ−ベンゾ［ｂ］チエノ−［２，３−ｄ］アゼピン誘導体
WO2016097761A1 (en)	2014-12-18	2016-06-23	Pulmocide Limited	4,5-dihydro-6h-thieno[3,2-d]benzazepine derivatives and their use to treat respiratory syncytial virus (rsv) infections
MY197231A (en)	2015-07-22	2023-06-06	Enanta Pharm Inc	Benzodiazepine derivatives as rsv inhibitors
EP3402799B1 (en)	2016-01-15	2022-05-04	Enanta Pharmaceuticals, Inc.	Heterocyclic compounds as rsv inhibitors
MY197217A (en) *	2016-02-03	2023-06-01	Janssen Sciences Ireland Uc	Combination products for the treatment of rsv
WO2017175000A1 (en) *	2016-04-08	2017-10-12	Pulmocide Limited	Compounds
US10398706B2 (en)	2017-01-06	2019-09-03	Enanta Pharmaceuticals, Inc.	Heteroaryldiazepine derivatives as RSV inhibitors
AU2018221820B2 (en)	2017-02-16	2023-11-02	Enanta Pharmaceuticals, Inc.	Processes for the preparation of benzodiazepine derivatives
US10752598B2 (en)	2017-06-07	2020-08-25	Enanta Pharmaceuticals, Inc.	Aryldiazepine derivatives as RSV inhibitors
WO2019006295A1 (en) *	2017-06-30	2019-01-03	Enanta Pharmaceuticals, Inc.	HETEROCYCLIC COMPOUNDS AS RSV INHIBITORS
WO2019006291A1 (en) *	2017-06-30	2019-01-03	Enanta Pharmaceuticals, Inc.	HETEROCYCLIC COMPOUNDS AS RSV INHIBITORS
WO2019067864A1 (en)	2017-09-29	2019-04-04	Enanta Pharmaceuticals, Inc.	PHARMACEUTICAL AGENTS IN COMBINATION AS INHIBITORS OF RSV
US10647711B2 (en)	2017-11-13	2020-05-12	Enanta Pharmaceuticals, Inc.	Azepin-2-one derivatives as RSV inhibitors
ES3043734T3 (en)	2017-11-13	2025-11-25	Enanta Pharm Inc	Processes for the resolution of benzodiazepin-2-one and benzoazepin-2-one derivatives
WO2019199908A1 (en) *	2018-04-11	2019-10-17	Enanta Pharmaceuticals, Inc.	Heterocyclic compounds as rsv inhibitors
CA3133300A1 (en)	2019-03-18	2020-09-24	Enanta Pharmaceuticals, Inc.	Benzodiazepine derivatives as rsv inhibitors
WO2020210246A1 (en) *	2019-04-09	2020-10-15	Enanta Pharmaceuticals, Inc,	Heterocyclic compounds as rsv inhibitors
US11505558B1 (en)	2019-10-04	2022-11-22	Enanta Pharmaceuticals, Inc.	Antiviral heterocyclic compounds
IL291834B1 (en)	2019-10-04	2026-02-01	Enanta Pharm Inc	Antiviral heterocyclic compounds
UY39032A (es)	2020-01-24	2021-07-30	Enanta Pharm Inc	Compuestos heterocíclicos como agentes antivirales
US11534439B2 (en)	2020-07-07	2022-12-27	Enanta Pharmaceuticals, Inc.	Dihydroquinoxaline and dihydropyridopyrazine derivatives as RSV inhibitors
WO2022086840A1 (en)	2020-10-19	2022-04-28	Enanta Pharmaceuticals, Inc.	Heterocyclic compounds as anti-viral agents
US12612412B2 (en)	2021-02-26	2026-04-28	Enanta Pharmaceuticals, Inc.	Antiviral heterocyclic compounds
IL305189A (en)	2021-02-26	2023-10-01	Enanta Pharm Inc	Heterocyclic antiviral compounds
AR129003A1 (es)	2022-04-07	2024-07-03	Enanta Pharm Inc	Compuestos heterocíclicos antivirales
WO2023211997A1 (en)	2022-04-27	2023-11-02	Enanta Pharmaceuticals, Inc.	Antiviral compounds

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5693635A (en)	1993-07-29	1997-12-02	American Cyanamid Company	Tricyclic benzazepine vasopressin antagonists
PT1177176E (pt)	1999-04-28	2006-08-31	Aventis Pharma Gmbh	Derivados de acidos triarilicos como ligandos de receptores ppar.
EP2240029A4 (en) *	2008-01-07	2012-08-22	Synta Pharmaceuticals Corp	COMPOUNDS FOR USE AGAINST INFLAMMATORY AND IMMUNOMIC DISEASES
WO2011005842A1 (en)	2009-07-09	2011-01-13	Gilead Sciences, Inc.	Anti-rsv compounds
JP5819305B2 (ja)	2009-10-13	2015-11-24	リガンド・ファーマシューティカルズ・インコーポレイテッド	造血成長因子模倣小分子化合物およびそれらの使用
KR101764952B1 (ko)	2010-07-29	2017-08-03	리겔 파마슈티칼스, 인크.	Ａｍｐｋ-활성화 헤테로시클릭 화합물 및 그의 사용 방법
WO2012129562A2 (en)	2011-03-24	2012-09-27	The Scripps Research Institute	Compounds and methods for inducing chondrogenesis
JP2017523988A (ja)	2014-08-05	2017-08-24	アリオスバイオファーマインク．	パラミクソウイルスを治療するための併用療法
JP6675407B2 (ja) *	2014-10-10	2020-04-01	プルモシデリミテド	新規５，６−ジヒドロ−４Ｈ−ベンゾ［ｂ］チエノ−［２，３−ｄ］アゼピン誘導体
EP3402799B1 (en)	2016-01-15	2022-05-04	Enanta Pharmaceuticals, Inc.	Heterocyclic compounds as rsv inhibitors
MY197217A (en)	2016-02-03	2023-06-01	Janssen Sciences Ireland Uc	Combination products for the treatment of rsv
WO2019006295A1 (en)	2017-06-30	2019-01-03	Enanta Pharmaceuticals, Inc.	HETEROCYCLIC COMPOUNDS AS RSV INHIBITORS
WO2019006291A1 (en)	2017-06-30	2019-01-03	Enanta Pharmaceuticals, Inc.	HETEROCYCLIC COMPOUNDS AS RSV INHIBITORS

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Publication number	Publication date
US9926335B2 (en)	2018-03-27
US20180179228A1 (en)	2018-06-28
BR112017005104A2 (pt)	2017-12-05
WO2016055791A1 (en)	2016-04-14
IL250823A0 (en)	2017-04-30
EP3204389A1 (en)	2017-08-16
CA2957868C (en)	2023-02-28
CN106852144B (zh)	2019-08-30
JP2017531038A (ja)	2017-10-19
EP3204388B1 (en)	2018-12-12
US20170305935A1 (en)	2017-10-26
US9732098B2 (en)	2017-08-15
EA201790796A1 (ru)	2017-09-29
US20180319820A1 (en)	2018-11-08
EP3204389B1 (en)	2019-06-26
MX2017004652A (es)	2017-06-19
JP6675407B2 (ja)	2020-04-01
EA201790796A8 (ru)	2018-10-31
CN106852144A (zh)	2017-06-13
US10273249B2 (en)	2019-04-30
EP3204388A1 (en)	2017-08-16
US20190202841A1 (en)	2019-07-04
SG11201701184WA (en)	2017-03-30
US20170190718A1 (en)	2017-07-06
AU2015329789B2 (en)	2019-09-26
BR112017005104B1 (pt)	2022-08-23
US10189863B2 (en)	2019-01-29
WO2016055792A1 (en)	2016-04-14
US20170355717A1 (en)	2017-12-14
JP2017531039A (ja)	2017-10-19
AU2015329789A1 (en)	2017-03-09
US10035810B2 (en)	2018-07-31
CA2957868A1 (en)	2016-04-14
US10472375B2 (en)	2019-11-12

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2017-03-07

PA0105

International application

Patent event date: 20170307

Patent event code: PA01051R01D

Comment text: International Patent Application