CN107207465A - 杂环化合物及其用途 - Google Patents
杂环化合物及其用途 Download PDFInfo
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- CN107207465A CN107207465A CN201580050829.5A CN201580050829A CN107207465A CN 107207465 A CN107207465 A CN 107207465A CN 201580050829 A CN201580050829 A CN 201580050829A CN 107207465 A CN107207465 A CN 107207465A
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- Prior art keywords
- compound
- prepare compound
- alkyl
- hydrogen
- heteroaryl
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- 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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- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
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CN110381949A (zh) * | 2017-01-10 | 2019-10-25 | 石全 | 杂环化合物及其用途 |
CN111138417A (zh) * | 2019-12-18 | 2020-05-12 | 浙江工业大学 | 一种三氮唑修饰的5-氟-2,4-嘧啶二胺类化合物及其应用 |
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IL302338A (en) * | 2017-09-08 | 2023-06-01 | Univ Leland Stanford Junior | ENPP1 inhibitors and their use for cancer treatment |
WO2020060268A1 (ko) | 2018-09-20 | 2020-03-26 | 한미약품 주식회사 | 상피세포 성장인자 수용체 돌연변이 저해 효과를 갖는 신규 융합 피리미딘 골격 설폰아마이드 유도체 |
MA54879A (fr) * | 2019-02-01 | 2021-12-08 | Univ Leland Stanford Junior | Inhibiteurs d'enpp1 et méthodes de modulation de réponse immunitaire |
WO2024101337A1 (ja) * | 2022-11-07 | 2024-05-16 | 国立大学法人京都大学 | キナゾリン誘導体 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS4936700A (zh) * | 1972-08-16 | 1974-04-05 | ||
WO1993020078A1 (en) * | 1992-04-03 | 1993-10-14 | The Upjohn Company | Pharmaceutically active bicyclic-heterocyclic amines |
WO2008005538A2 (en) * | 2006-07-05 | 2008-01-10 | Exelixis, Inc. | Methods of using igf1r and abl kinase modulators |
WO2009123221A1 (ja) * | 2008-03-31 | 2009-10-08 | 全薬工業株式会社 | 細胞保護作用を有するピリミジン誘導体およびその用途 |
WO2014074517A1 (en) * | 2012-11-08 | 2014-05-15 | Emory University | Cellular compositions used to restore stem cell or progenitor cell function and methods related thereto |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6156758A (en) * | 1999-09-08 | 2000-12-05 | Isis Pharmaceuticals, Inc. | Antibacterial quinazoline compounds |
JP4936700B2 (ja) | 2005-09-29 | 2012-05-23 | Ntn株式会社 | 車輪用軸受装置およびその製造方法 |
CN102015717A (zh) * | 2008-03-28 | 2011-04-13 | 奥蒂瑞斯治疗公司 | 趋化因子受体调节剂 |
SI2268635T1 (sl) | 2008-04-21 | 2015-10-30 | Taigen Biotechnology Co., Ltd. | Heterociklične spojine |
WO2010046780A2 (en) | 2008-10-22 | 2010-04-29 | Institut Pasteur Korea | Anti viral compounds |
GB201015411D0 (en) | 2010-09-15 | 2010-10-27 | Univ Leuven Kath | Anti-cancer activity of novel bicyclic heterocycles |
WO2013046136A1 (en) | 2011-09-27 | 2013-04-04 | Novartis Ag | 3-pyrimidin-4-yl-oxazolidin-2-ones as inhibitors of mutant idh |
CN104379180A (zh) | 2012-04-10 | 2015-02-25 | 佐治亚州立大学研究基金会公司 | 用cyld抑制剂治疗中耳炎及其它病状的组合物和方法 |
MX365114B (es) | 2012-10-10 | 2019-05-23 | Janssen Sciences Ireland Uc | Derivados pirrolo[3,2-d]pirimidinicos para el tratamiento de infecciones viricas y otras enfermedades. |
-
2015
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Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS4936700A (zh) * | 1972-08-16 | 1974-04-05 | ||
WO1993020078A1 (en) * | 1992-04-03 | 1993-10-14 | The Upjohn Company | Pharmaceutically active bicyclic-heterocyclic amines |
WO2008005538A2 (en) * | 2006-07-05 | 2008-01-10 | Exelixis, Inc. | Methods of using igf1r and abl kinase modulators |
WO2009123221A1 (ja) * | 2008-03-31 | 2009-10-08 | 全薬工業株式会社 | 細胞保護作用を有するピリミジン誘導体およびその用途 |
WO2014074517A1 (en) * | 2012-11-08 | 2014-05-15 | Emory University | Cellular compositions used to restore stem cell or progenitor cell function and methods related thereto |
Non-Patent Citations (6)
Title |
---|
GERI A. SAWADA等: "Increased Lipophilicity and Subsequent Cell Partitioning Decrease Passive Transcellular Diffusion of Novel, Highly Lipophilic Antioxidants", 《THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS》 * |
STN-REGISTRY: "702635-05-0", 《STN-REGISTRY》 * |
STN-REGISTRY: "744986-10-5", 《STN-REGISTRY》 * |
STN-REGISTRY: "746594-35-4", 《STN-REGISTRY》 * |
STN-REGISTRY: "923221-53-8", 《STN-REGISTRY》 * |
WOLFGANG K.-D等: "Solid-phase synthesis of 2,6,8-trisubstituted purines", 《TETRAHEDRON LETTERS》 * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110381949A (zh) * | 2017-01-10 | 2019-10-25 | 石全 | 杂环化合物及其用途 |
CN110381949B (zh) * | 2017-01-10 | 2023-12-08 | 财团法人卫生研究院 | 杂环化合物及其用途 |
CN111138417A (zh) * | 2019-12-18 | 2020-05-12 | 浙江工业大学 | 一种三氮唑修饰的5-氟-2,4-嘧啶二胺类化合物及其应用 |
CN111138417B (zh) * | 2019-12-18 | 2021-03-23 | 浙江工业大学 | 一种三氮唑修饰的5-氟-2,4-嘧啶二胺类化合物及其应用 |
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TW201615637A (zh) | 2016-05-01 |
BR112017005713A2 (pt) | 2018-01-23 |
NZ730195A (en) | 2023-12-22 |
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US9862703B2 (en) | 2018-01-09 |
WO2016048861A2 (en) | 2016-03-31 |
CN107207465B (zh) | 2021-09-10 |
AU2015321654B2 (en) | 2019-10-31 |
KR20170072894A (ko) | 2017-06-27 |
RU2017109355A (ru) | 2018-10-24 |
JP6615207B2 (ja) | 2019-12-04 |
CA2962329C (en) | 2023-12-19 |
KR102509431B1 (ko) | 2023-03-13 |
EP3197885B1 (en) | 2020-11-18 |
CA2962329A1 (en) | 2016-03-31 |
ES2849998T3 (es) | 2021-08-24 |
TWI598348B (zh) | 2017-09-11 |
RU2017109355A3 (zh) | 2019-04-04 |
US20180009786A1 (en) | 2018-01-11 |
EP3197885A2 (en) | 2017-08-02 |
AU2015321654A1 (en) | 2017-04-06 |
BR112017005713B1 (pt) | 2023-09-26 |
US20160083369A1 (en) | 2016-03-24 |
WO2016048861A3 (en) | 2016-09-15 |
US9926298B2 (en) | 2018-03-27 |
EP3197885A4 (en) | 2018-02-21 |
JP2017530193A (ja) | 2017-10-12 |
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