CN116472034B - 茚化合物、其药物组合物及其治疗应用 - Google Patents

茚化合物、其药物组合物及其治疗应用

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Publication number
CN116472034B
CN116472034B CN202180055583.6A CN202180055583A CN116472034B CN 116472034 B CN116472034 B CN 116472034B CN 202180055583 A CN202180055583 A CN 202180055583A CN 116472034 B CN116472034 B CN 116472034B
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methyl
inden
methylene
phenyl
fluoro
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CN116472034A (zh
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苏迎
张晓坤
陈梓文
陈庆镇
王海山
章新道
曾志平
周雨琪
颜志强
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Tengji Xiamen Biomedical Technology Co ltd
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Tengji Xiamen Biomedical Technology Co ltd
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999016453A1 (en) * 1997-09-26 1999-04-08 Eli Lilly And Company Method for the treatment of cystic fibrosis
DE10163426A1 (de) * 2001-12-21 2003-07-03 Max Planck Gesellschaft Pharmakologisch wirksame Inden-Derivate
CN107050007A (zh) * 2010-05-06 2017-08-18 桑福德 - 伯纳姆医学研究所 涉及类视黄醇受体选择性通路的方法和组合物

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US6214876B1 (en) * 1994-07-21 2001-04-10 Eli Lilly And Company Indene-1-acetamide sPLA2 inhibitors
CA2289102A1 (en) 1997-05-07 1998-11-12 Sugen, Inc. 2-indolinone derivatives as modulators of protein kinase activity
DK2250161T3 (da) * 2008-01-18 2014-01-27 Atopix Therapeutics Ltd Forbindelser med CRTH2-antagonistaktivitet
US20200237710A1 (en) 2019-01-25 2020-07-30 Alfred Ordman Synergistic composition of vitamin c and vitamin k1, and compositions thereof for the treatment of cancer

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999016453A1 (en) * 1997-09-26 1999-04-08 Eli Lilly And Company Method for the treatment of cystic fibrosis
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CN107050007A (zh) * 2010-05-06 2017-08-18 桑福德 - 伯纳姆医学研究所 涉及类视黄醇受体选择性通路的方法和组合物

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
舒林酸衍生物K-80003靶向RXRα抗炎机制研究;刘帅;中国优秀硕士学位论文全文数据库;20190615;第医药卫生科技辑卷;E079-24，摘要、表1 *

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