TWI778951B - Ｔｌｒ７促效劑的馬來酸鹽、其晶型ｃ、晶型ｄ、晶型ｅ、其製備方法、包含其的藥物組合物及其用途 - Google Patents

Ｔｌｒ７促效劑的馬來酸鹽、其晶型ｃ、晶型ｄ、晶型ｅ、其製備方法、包含其的藥物組合物及其用途 Download PDF

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Publication number: TWI778951B
Authority: TW; Taiwan
Prior art keywords: crystal form; formula; ray powder; compound; powder diffraction
Prior art date: 2016-02-05

Application number

TW106103694A

Other languages

English (en)

Chinese (zh)

Other versions

TW201728588A (zh

Inventor

照中丁

孫飛

胡迎虎

周義龍

王崢

楊玲

Original Assignee

大陸商正大天晴藥業集團股份有限公司

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2016-02-05

Filing date

2017-02-03

Publication date

2022-10-01

2017-02-03 Application filed by 大陸商正大天晴藥業集團股份有限公司 filed Critical 大陸商正大天晴藥業集團股份有限公司

2017-08-16 Publication of TW201728588A publication Critical patent/TW201728588A/zh

2022-10-01 Application granted granted Critical

2022-10-01 Publication of TWI778951B publication Critical patent/TWI778951B/zh

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TW106103694A 2016-02-05 2017-02-03 Ｔｌｒ７促效劑的馬來酸鹽、其晶型ｃ、晶型ｄ、晶型ｅ、其製備方法、包含其的藥物組合物及其用途 TWI778951B (zh)

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Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN107043378A (zh) *	2016-02-05	2017-08-15	正大天晴药业集团股份有限公司	一种吡咯并[3,2-d]嘧啶类化合物的制备方法及其中间体
CN107043379A (zh)	2016-02-05	2017-08-15	正大天晴药业集团股份有限公司	一种tlr7激动剂的晶型a、其制备方法和医药用途
CN107043380A (zh)	2016-02-05	2017-08-15	正大天晴药业集团股份有限公司	一种tlr7激动剂的马来酸盐、其晶型c、晶型d、晶型e、制备方法和用途
AU2019272478B2 (en) *	2018-05-25	2024-06-06	Chia Tai Tianqing Pharmaceutical Group Co., Ltd.	TLR7 agonist and pharmaceutical combination thereof for treating lung cancer
WO2020162705A1 (ko)	2019-02-08	2020-08-13	성균관대학교산학협력단	톨-유사 수용체 7 또는 8 작용자와 콜레스테롤의 결합체 및 그 용도
CA3170551A1 (en)	2020-03-02	2021-09-10	Yong Taik Lim	Live-pathogen-mimetic nanoparticles based on pathogen cell wall skeleton, and production method thereof
US20230277525A1 (en)	2020-08-04	2023-09-07	Progeneer Inc	Conjugate of functional drug and toll-like receptor 7 or 8 agonist of which active site is temporarily inactivated and use thereof
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US20230346924A1 (en)	2020-08-04	2023-11-02	Progeneer Inc.	Mrna vaccine comprising adjuvant capable of kinetic control

Citations (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN104780923A (zh) *	2012-11-20	2015-07-15	葛兰素史克有限责任公司	新颖的化合物
CN104780924A (zh) *	2012-11-20	2015-07-15	葛兰素史克有限责任公司	新颖的化合物
CN104837840A (zh) *	2012-10-10	2015-08-12	爱尔兰詹森科学公司	用于治疗病毒感染及其他疾病的吡咯并[3,2-d]嘧啶衍生物
WO2015168269A1 (en) *	2014-05-01	2015-11-05	Novartis Ag	Compounds and compositions as toll-like receptor 7 agonists

Family Cites Families (22)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP3376479B2 (ja) *	1991-08-12	2003-02-10	武田薬品工業株式会社	縮合ピリミジン誘導体、その製造法および用途
ES2232871T3 (es)	1996-07-03	2005-06-01	Sumitomo Pharmaceuticals Company, Limited	Nuevos derivados de purina.
DE69817393T2 (de)	1997-11-28	2004-06-17	Sumitomo Pharmaceuticals Co., Ltd.	Neue heterozyklische verbindungen
CN101304748A (zh)	2005-08-22	2008-11-12	加利福尼亚大学董事会	Tlr激动剂
CA2691444C (en)	2007-06-29	2016-06-14	Gilead Sciences, Inc.	Purine derivatives and their use as modulators of toll-like receptor 7
ES2359123T3 (es)	2007-08-03	2011-05-18	Pfizer Limited	Imidazopiridinonas.
RS53347B (sr)	2008-12-09	2014-10-31	Gilead Sciences, Inc.	Modulatori toll-sličnih receptora
WO2012106522A2 (en)	2011-02-04	2012-08-09	Duquesne University Of The Holy Spirit	Bicyclic and tricyclic pyrimidine tyrosine kinase inhibitors with antitubulin activity and methods of treating a patient
EP2800569B1 (en)	2012-01-05	2018-07-25	Northeastern University	Allosteric modulators of cb1 cannabinoid receptors
EA028480B1 (ru)	2012-11-20	2017-11-30	ГЛАКСОСМИТКЛАЙН ЭлЭлСи	Новые соединения
KR20160124157A (ko)	2014-02-20	2016-10-26	글락소스미스클라인 인털렉츄얼 프로퍼티 (넘버 2) 리미티드	인간 인터페론의 유도인자로서의 피롤로[3,2]피리미딘 유도체
ES2908150T3 (es)	2014-05-01	2022-04-27	Novartis Ag	Compuestos y composiciones como agonistas del receptor de tipo Toll 7
HRP20210927T1 (hr) *	2014-08-15	2021-09-03	Chia Tai Tianqing Pharmaceutical Group Co., Ltd.	Spojevi pirolopirimidina koje se koriste kao agonist tlr7
CN105367576A (zh) *	2014-08-15	2016-03-02	正大天晴药业集团股份有限公司	作为tlr7激动剂的吡咯并嘧啶化合物
CN105732635A (zh)	2014-12-29	2016-07-06	南京明德新药研发股份有限公司	一类Toll样受体7激动剂
MX2018005388A (es)	2015-11-05	2018-08-16	Basf Se	Oxadiazoles sustituidos para combatir hongos fitopatogenos.
UA121345C2 (uk)	2015-11-05	2020-05-12	Чіа Тай Тяньцин Фармасьютікал Груп Ко., Лтд.	7-(тіазол-5-іл)піролопіримідин як агоніст рецептора tlr7
TWI714661B (zh)	2015-11-05	2021-01-01	法商賽諾菲公司	新穎念珠藻素化合物及接合物、其製備與其治療用途
CN107043380A (zh)	2016-02-05	2017-08-15	正大天晴药业集团股份有限公司	一种tlr7激动剂的马来酸盐、其晶型c、晶型d、晶型e、制备方法和用途
CN107043379A (zh)	2016-02-05	2017-08-15	正大天晴药业集团股份有限公司	一种tlr7激动剂的晶型a、其制备方法和医药用途
CN107043377A (zh)	2016-02-05	2017-08-15	正大天晴药业集团股份有限公司	一种tlr7激动剂的三氟乙酸盐、晶型b及其制备方法、药物组合物和用途
CN107043378A (zh) *	2016-02-05	2017-08-15	正大天晴药业集团股份有限公司	一种吡咯并[3,2-d]嘧啶类化合物的制备方法及其中间体

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Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN104837840A (zh) *	2012-10-10	2015-08-12	爱尔兰詹森科学公司	用于治疗病毒感染及其他疾病的吡咯并[3,2-d]嘧啶衍生物
CN104780923A (zh) *	2012-11-20	2015-07-15	葛兰素史克有限责任公司	新颖的化合物
CN104780924A (zh) *	2012-11-20	2015-07-15	葛兰素史克有限责任公司	新颖的化合物
WO2015168269A1 (en) *	2014-05-01	2015-11-05	Novartis Ag	Compounds and compositions as toll-like receptor 7 agonists

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Publication number	Publication date
HK1259175A1 (zh)	2019-11-29
AU2017215800B2 (en)	2020-08-20
CA3013682A1 (en)	2017-08-10
UA123781C2 (uk)	2021-06-02
AU2017215800A1 (en)	2018-08-30
ZA201805185B (en)	2024-08-28
NZ745231A (en)	2022-07-29
SG11201806682TA (en)	2018-09-27
EP3412671A1 (en)	2018-12-12
MX2018009500A (es)	2018-12-11
JP2019505532A (ja)	2019-02-28
CA3013682C (en)	2022-06-21
US20200368241A1 (en)	2020-11-26
ES2834303T3 (es)	2021-06-17
US10780091B2 (en)	2020-09-22
CL2018002089A1 (es)	2018-12-07
PH12018501644A1 (en)	2019-06-03
CN108602830A (zh)	2018-09-28
JP6898336B2 (ja)	2021-07-07
EA038794B1 (ru)	2021-10-20
DK3412671T3 (da)	2020-11-09
MY196762A (en)	2023-05-03
MX374295B (es)	2025-03-06
EA201891770A1 (ru)	2019-01-31
US20190070179A1 (en)	2019-03-07
PH12018501644B1 (en)	2022-09-07
BR112018015881A2 (pt)	2018-12-26
AR107547A1 (es)	2018-05-09
IL260965B (en)	2022-02-01
CN107043380A (zh)	2017-08-15
KR20180104116A (ko)	2018-09-19
HUE052211T2 (hu)	2021-04-28
KR102393279B1 (ko)	2022-05-02
TW201728588A (zh)	2017-08-16
WO2017133683A1 (zh)	2017-08-10
CN108602830B (zh)	2020-07-28
EP3412671A4 (en)	2019-07-24
EP3412671B1 (en)	2020-09-16

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Publication	Publication Date	Title
TWI778951B (zh)	2022-10-01	Ｔｌｒ７促效劑的馬來酸鹽、其晶型ｃ、晶型ｄ、晶型ｅ、其製備方法、包含其的藥物組合物及其用途
TWI754629B (zh)	2022-02-11	Ｔｌｒ７促效劑的晶型ａ、其製備方法、藥物組合物和用途
TWI778952B (zh)	2022-10-01	Ｔｌｒ７促效劑的三氟乙酸鹽、其晶型ｂ、其製備方法、包含其的藥物組合物及其用途
HK1259175B (zh)	2021-02-19	一种tlr7激动剂的马来酸盐、其晶型c、晶型d、晶型e及其制备方法和用途
HK1259170B (zh)	2021-06-11	一种tlr7激动剂的晶型a、其制备方法和用途
HK1259182B (zh)	2021-02-19	一种tlr7激动剂的三氟乙酸盐、晶型b、制备方法和用途