CN107709338A - 吲哚胺2,3‑双加氧酶的抑制剂 - Google Patents
吲哚胺2,3‑双加氧酶的抑制剂 Download PDFInfo
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- CN107709338A CN107709338A CN201680039221.7A CN201680039221A CN107709338A CN 107709338 A CN107709338 A CN 107709338A CN 201680039221 A CN201680039221 A CN 201680039221A CN 107709338 A CN107709338 A CN 107709338A
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Classifications
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- C—CHEMISTRY; METALLURGY
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- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K33/22—Boron compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
Landscapes
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- Organic Chemistry (AREA)
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- Veterinary Medicine (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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PCT/IB2016/053947 WO2017002078A1 (en) | 2015-07-02 | 2016-06-30 | Inhibitors of indoleamine 2,3-dioxygenase |
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CN108530444A (zh) * | 2018-06-11 | 2018-09-14 | 中国药科大学 | 一种新型nampt和ido双重抑制剂及其制备方法和医药用途 |
CN110156629A (zh) * | 2019-05-30 | 2019-08-23 | 广州药本君安医药科技股份有限公司 | 丙卡巴肼的合成方法 |
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DK3873903T3 (da) | 2018-10-31 | 2024-04-02 | Gilead Sciences Inc | Substituerede 6-azabenzimidazolforbindelser som hpk1-hæmmere |
TW202136261A (zh) | 2018-10-31 | 2021-10-01 | 美商基利科學股份有限公司 | 經取代之6-氮雜苯并咪唑化合物 |
WO2020237025A1 (en) | 2019-05-23 | 2020-11-26 | Gilead Sciences, Inc. | Substituted exo-methylene-oxindoles which are hpk1/map4k1 inhibitors |
BR112023017582A2 (pt) | 2021-03-05 | 2023-12-05 | Univ Basel | Composições para o tratamento de doenças ou condições associadas ao ebv |
EP4052705A1 (en) | 2021-03-05 | 2022-09-07 | Universität Basel Vizerektorat Forschung | Compositions for the treatment of ebv associated diseases or conditions |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101212967A (zh) * | 2005-05-10 | 2008-07-02 | 因塞特公司 | 吲哚胺2,3-双加氧酶调节剂及其用法 |
CN102164902A (zh) * | 2008-07-08 | 2011-08-24 | 因塞特公司 | 作为吲哚胺2,3-双加氧酶的抑制剂的1,2,5-二唑 |
WO2014066834A1 (en) * | 2012-10-26 | 2014-05-01 | The University Of Chicago | Synergistic combination of immunologic inhibitors for the treatment of cancer |
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GB427857A (en) | 1934-08-02 | 1935-05-01 | Newsum Sons & Company Ltd H | A new or improved system of construction for skeleton structures, particularly vehicle body frames and door frames |
US4107288A (en) | 1974-09-18 | 1978-08-15 | Pharmaceutical Society Of Victoria | Injectable compositions, nanoparticles useful therein, and process of manufacturing same |
US5145684A (en) | 1991-01-25 | 1992-09-08 | Sterling Drug Inc. | Surface modified drug nanoparticles |
IL157940A0 (en) | 2001-03-19 | 2004-03-28 | Ono Pharmaceutical Co | Drugs containing triazaspiro [5.5] undecane derivatives as the active ingredient |
KR20080042158A (ko) | 2005-08-31 | 2008-05-14 | 셀진 코포레이션 | 이소인돌-이미드 화합물과 이를 포함하는 조성물 및 이를이용한 방법 |
AU2011329485A1 (en) * | 2010-11-18 | 2013-04-18 | Glaxo Group Limited | Compounds |
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- 2016-06-30 BR BR112017028456A patent/BR112017028456A2/pt not_active Application Discontinuation
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101212967A (zh) * | 2005-05-10 | 2008-07-02 | 因塞特公司 | 吲哚胺2,3-双加氧酶调节剂及其用法 |
CN102164902A (zh) * | 2008-07-08 | 2011-08-24 | 因塞特公司 | 作为吲哚胺2,3-双加氧酶的抑制剂的1,2,5-二唑 |
WO2014066834A1 (en) * | 2012-10-26 | 2014-05-01 | The University Of Chicago | Synergistic combination of immunologic inhibitors for the treatment of cancer |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108530444A (zh) * | 2018-06-11 | 2018-09-14 | 中国药科大学 | 一种新型nampt和ido双重抑制剂及其制备方法和医药用途 |
CN110156629A (zh) * | 2019-05-30 | 2019-08-23 | 广州药本君安医药科技股份有限公司 | 丙卡巴肼的合成方法 |
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ES2752455T3 (es) | 2020-04-06 |
AU2016285483A1 (en) | 2018-01-04 |
BR112017028456A2 (pt) | 2018-08-28 |
RU2018101431A (ru) | 2019-08-05 |
EP3317287A1 (en) | 2018-05-09 |
KR20180022988A (ko) | 2018-03-06 |
AU2016285483B2 (en) | 2018-07-19 |
US10239894B2 (en) | 2019-03-26 |
WO2017002078A1 (en) | 2017-01-05 |
US20180298035A1 (en) | 2018-10-18 |
CA2990335A1 (en) | 2017-01-05 |
EP3317287B1 (en) | 2019-07-31 |
JP2018521056A (ja) | 2018-08-02 |
JP6654208B2 (ja) | 2020-02-26 |
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