CN115087653A - 一种醛基类化合物的药物用途 - Google Patents
一种醛基类化合物的药物用途 Download PDFInfo
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- CN115087653A CN115087653A CN202080095393.2A CN202080095393A CN115087653A CN 115087653 A CN115087653 A CN 115087653A CN 202080095393 A CN202080095393 A CN 202080095393A CN 115087653 A CN115087653 A CN 115087653A
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- 238000002360 preparation method Methods 0.000 claims abstract description 5
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- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims abstract description 4
- 125000001424 substituent group Chemical group 0.000 claims description 83
- 125000001072 heteroaryl group Chemical group 0.000 claims description 47
- 125000004432 carbon atom Chemical group C* 0.000 claims description 31
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 31
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 30
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 30
- 229910052760 oxygen Inorganic materials 0.000 claims description 29
- 229910052799 carbon Inorganic materials 0.000 claims description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
- 125000000304 alkynyl group Chemical group 0.000 claims description 27
- 239000001301 oxygen Substances 0.000 claims description 27
- 125000000217 alkyl group Chemical group 0.000 claims description 26
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- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 22
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- 125000005842 heteroatom Chemical group 0.000 claims description 17
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- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 claims description 8
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- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 6
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Abstract
如通式I所示的醛类化合物,及其药物组合物、药用盐、对映体、非对映体及外消旋化合物在作为2019新型冠状病毒(2019‑nCov)3CL蛋白酶抑制剂在制备治疗和/或预防、缓解由2019新型冠状病毒感染引起的呼吸道感染、肺炎等相关疾病的药物中的用途。
Description
PCT国内申请,说明书已公开。
Claims (15)
- PCT国内申请,权利要求书已公开。
Applications Claiming Priority (3)
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CN2020100774633 | 2020-01-29 | ||
CN202010077463.3A CN113181339B (zh) | 2020-01-29 | 2020-01-29 | 一种醛基类化合物的药物用途 |
PCT/CN2020/081481 WO2021151265A1 (zh) | 2020-01-29 | 2020-03-26 | 一种醛基类化合物的药物用途 |
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CN115087653A true CN115087653A (zh) | 2022-09-20 |
CN115087653B CN115087653B (zh) | 2023-11-17 |
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WO2023198067A1 (zh) * | 2022-04-11 | 2023-10-19 | 上海科技大学 | 一种化合物及其在制备治疗肠道病毒相关疾病的药物中的应用 |
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Publication number | Priority date | Publication date | Assignee | Title |
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CN113181339B (zh) * | 2020-01-29 | 2022-02-22 | 中国科学院上海药物研究所 | 一种醛基类化合物的药物用途 |
CA3183740A1 (en) | 2020-06-10 | 2021-12-16 | Aligos Therapeutics, Inc. | Anti-viral compounds for treating coronavirus, picornavirus, and norovirus infections |
WO2022268111A1 (zh) * | 2021-06-25 | 2022-12-29 | 前沿生物药业(南京)股份有限公司 | 抗病毒药物组合物及其制备方法和应用 |
US11851422B2 (en) | 2021-07-09 | 2023-12-26 | Aligos Therapeutics, Inc. | Anti-viral compounds |
CA3230035A1 (en) * | 2021-09-30 | 2023-04-06 | Xiangrui Jiang | Cyano compounds, and preparation method therefor and use thereof |
WO2023136277A1 (ja) * | 2022-01-12 | 2023-07-20 | 株式会社Preferred Networks | 化合物及びその使用 |
CN114957383A (zh) * | 2022-04-01 | 2022-08-30 | 中国科学院上海药物研究所 | 一种拟肽类化合物及其制备方法、药物组合物和用途 |
CN115466225A (zh) * | 2022-08-16 | 2022-12-13 | 中国科学院上海药物研究所 | 一种酰胺类化合物及其制备方法、药物组合物和用途 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013049382A2 (en) * | 2011-09-27 | 2013-04-04 | Kansas State University Research Foundation | Broad-spectrum antivirals against 3c or 3c-like proteases of picornavirus-like supercluster: picornaviruses, caliciviruses and coronaviruses |
WO2013166319A1 (en) * | 2012-05-02 | 2013-11-07 | Kansas State University Research Foundation | Macrocyclic and peptidomimetic compounds as broad-spectrum antivirals against 3c or 3c-like proteases of picornaviruses, caliciviruses and coronaviruses |
CN106928206A (zh) * | 2015-12-31 | 2017-07-07 | 中国科学院上海药物研究所 | 醛基类化合物及其制法和用途 |
WO2020030143A1 (zh) * | 2018-08-09 | 2020-02-13 | 中国科学院上海药物研究所 | 酮酰胺类化合物及其制备方法、药物组合物和用途 |
CN113181339A (zh) * | 2020-01-29 | 2021-07-30 | 中国科学院上海药物研究所 | 一种醛基类化合物的药物用途 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102838523A (zh) * | 2011-06-23 | 2012-12-26 | 南开大学 | 抗肠病毒71(ev71)戊内酰胺类化合物及其制备方法和用途 |
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Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013049382A2 (en) * | 2011-09-27 | 2013-04-04 | Kansas State University Research Foundation | Broad-spectrum antivirals against 3c or 3c-like proteases of picornavirus-like supercluster: picornaviruses, caliciviruses and coronaviruses |
WO2013166319A1 (en) * | 2012-05-02 | 2013-11-07 | Kansas State University Research Foundation | Macrocyclic and peptidomimetic compounds as broad-spectrum antivirals against 3c or 3c-like proteases of picornaviruses, caliciviruses and coronaviruses |
CN106928206A (zh) * | 2015-12-31 | 2017-07-07 | 中国科学院上海药物研究所 | 醛基类化合物及其制法和用途 |
WO2020030143A1 (zh) * | 2018-08-09 | 2020-02-13 | 中国科学院上海药物研究所 | 酮酰胺类化合物及其制备方法、药物组合物和用途 |
CN110818691A (zh) * | 2018-08-09 | 2020-02-21 | 中国科学院上海药物研究所 | 酮酰胺类化合物及其制备方法、药物组合物和用途 |
CN113181339A (zh) * | 2020-01-29 | 2021-07-30 | 中国科学院上海药物研究所 | 一种醛基类化合物的药物用途 |
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WO2023198067A1 (zh) * | 2022-04-11 | 2023-10-19 | 上海科技大学 | 一种化合物及其在制备治疗肠道病毒相关疾病的药物中的应用 |
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