CN1668613A - 作为细胞周期蛋白依赖型激酶抑制剂的黄酮衍生物 - Google Patents
作为细胞周期蛋白依赖型激酶抑制剂的黄酮衍生物 Download PDFInfo
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- CN1668613A CN1668613A CNA038163241A CN03816324A CN1668613A CN 1668613 A CN1668613 A CN 1668613A CN A038163241 A CNA038163241 A CN A038163241A CN 03816324 A CN03816324 A CN 03816324A CN 1668613 A CN1668613 A CN 1668613A
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- Prior art keywords
- methyl
- tetramethyleneimine
- cis
- phenyl
- methylol
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Images
Classifications
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Animal Behavior & Ethology (AREA)
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- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
Description
编号 | 化合物编号 | IC50(μM) | IC50之比 | |
CDK4-细胞周期蛋白D1 | CDK2-细胞周期蛋白E | CDK2/E∶CDK4/D1 | ||
1 | 67 | 0.13 | 4.25 | 32.7 |
2 | 31 | 0.28 | 8.75 | 31.2 |
3 | 54 | 0.08 | 6.00 | 75.0 |
4 | Flavopiridol | 0.04 | 0.18 | 4.5 |
编号 | 化合物编号 | IC50(μM) | |||||
HeLa子宫颈 | MCF-7乳腺 | PC-3前列腺 | MDAMB-231乳腺 | H460肺 | U-937组织细胞淋巴瘤(单核细胞) | ||
1 | 12 | 0.1-0.5 | 0.5-1 | 0.5-1 | 0.5-1 | 5.0-10 | 0.1-1 |
++ | NT | ++ | NT | NT | + | ||
2 | 17 | 0.1-1 | 0.5-1 | 1.0-10 | 0.1 | >10 | 0.1-1 |
+ | + | NT | NT | NT | + | ||
3 | 101 | 0.01-1 | 0.01-1 | 0.01-1 | 0.01-1 | >10 | <0.1 |
++ | NT | ++ | NT | NT | + | ||
4 | 104 | >10 | >10 | 1.0-10 | >10 | NA | 1.0-10 |
NT | NT | NT | NT | NT | NT | ||
5 | Flavopiridol | 0.1-0.5 | 0.5 | 0.05-0.1 | 0.1 | 0.05 | 0.1 |
+++ | + | ++ | ++ | + | ++ |
Claims (30)
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IN616/MUM/2002 | 2002-07-08 | ||
IN616MU2002 | 2002-07-08 | ||
PCT/IN2003/000234 WO2004004632A2 (en) | 2002-07-08 | 2003-07-07 | Flavone derivatives as inhibitors of cyclin-dependent kinases |
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CN1668613A true CN1668613A (zh) | 2005-09-14 |
CN1668613B CN1668613B (zh) | 2012-07-04 |
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EP (1) | EP1556375B1 (zh) |
JP (1) | JP4860148B2 (zh) |
KR (1) | KR100991920B1 (zh) |
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RU (1) | RU2334746C2 (zh) |
TW (1) | TWI331034B (zh) |
WO (1) | WO2004004632A2 (zh) |
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Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
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ES2309338T3 (es) | 2008-12-16 |
RU2334746C2 (ru) | 2008-09-27 |
JP2006502109A (ja) | 2006-01-19 |
EP1556375A2 (en) | 2005-07-27 |
AU2003272070B2 (en) | 2009-02-26 |
EP1556375B1 (en) | 2008-06-25 |
AU2003272070A1 (en) | 2004-01-23 |
DK1556375T3 (da) | 2008-11-03 |
PT1556375E (pt) | 2008-10-03 |
BR0312633A (pt) | 2005-07-19 |
ZA200500138B (en) | 2006-02-22 |
DE60321808D1 (de) | 2008-08-07 |
KR20050017110A (ko) | 2005-02-21 |
JP4860148B2 (ja) | 2012-01-25 |
IL166153A0 (en) | 2006-01-15 |
WO2004004632A3 (en) | 2004-09-16 |
IL166153A (en) | 2009-11-18 |
CN1668613B (zh) | 2012-07-04 |
KR100991920B1 (ko) | 2010-11-04 |
NZ537518A (en) | 2008-02-29 |
AR041184A1 (es) | 2005-05-04 |
TW200406202A (en) | 2004-05-01 |
ATE399162T1 (de) | 2008-07-15 |
TWI331034B (en) | 2010-10-01 |
WO2004004632A8 (en) | 2005-03-24 |
CA2492130C (en) | 2011-09-06 |
CA2492130A1 (en) | 2004-01-15 |
RU2005102939A (ru) | 2005-09-10 |
WO2004004632A2 (en) | 2004-01-15 |
MXPA05000388A (es) | 2005-09-30 |
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