JP2014527979A - 増殖性疾患を治療するためのストリゴラクトンおよびストリゴラクトンアナログの使用 - Google Patents
増殖性疾患を治療するためのストリゴラクトンおよびストリゴラクトンアナログの使用 Download PDFInfo
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- JP2014527979A JP2014527979A JP2014531375A JP2014531375A JP2014527979A JP 2014527979 A JP2014527979 A JP 2014527979A JP 2014531375 A JP2014531375 A JP 2014531375A JP 2014531375 A JP2014531375 A JP 2014531375A JP 2014527979 A JP2014527979 A JP 2014527979A
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- methyl
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- strigolactone
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- dihydrofuran
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- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/93—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems condensed with a ring other than six-membered
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
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- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
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- 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
- C07D405/02—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
- C07D405/12—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 linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
Landscapes
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- Health & Medical Sciences (AREA)
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- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
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| US201261614965P | 2012-03-23 | 2012-03-23 | |
| US61/614,965 | 2012-03-23 | ||
| PCT/IL2012/050381 WO2013042124A1 (en) | 2011-09-21 | 2012-09-20 | Use of strigolactones and strigolactone analogs for treating proliferative conditions |
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| US11458154B2 (en) | 2013-09-06 | 2022-10-04 | Vanda Pharmaceuticals Inc. | Treatment of CYR61- and VEGF-mediated conditions |
| US20180235213A1 (en) * | 2015-05-14 | 2018-08-23 | The State of Israel Ministry of Agriculture & Rural Develop. Agricultural Research Organization | Plant hormone application |
| GB201615544D0 (en) * | 2016-09-13 | 2016-10-26 | Syngenta Participations Ag | Plant Growth regulator compounds |
| CN108558796B (zh) * | 2018-05-07 | 2020-04-07 | 南开大学 | 一类羟亚甲基氢化茚酮衍生物及其制备方法和用途 |
| CN108675974B (zh) * | 2018-05-07 | 2020-04-07 | 南开大学 | 一类独脚金内酯衍生物及其制备方法和用途 |
| EP3876927A1 (en) * | 2018-11-08 | 2021-09-15 | Universita' Degli Studi di Torino | Strigolactones for use in preventing and/or treating infections caused by viruses of the herpesviridae family |
| CN117843651B (zh) * | 2024-01-03 | 2024-09-10 | 盐城工学院 | 一种含有三氟甲基季碳中心的四氢呋喃并[3,2-b]吲哚啉类化合物及其制备方法 |
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| WO2005077177A2 (fr) * | 2004-02-10 | 2005-08-25 | Universite Paul Sabatier Toulouse Iii | Modulateurs de developpement des champignons mycorhiziens a arbuscules, et applications |
| JP2010529975A (ja) * | 2007-06-15 | 2010-09-02 | バイエル・クロツプサイエンス・エス・アー | ストリゴラクトン誘導体と殺菌剤化合物を含んでいる殺有害生物剤組成物 |
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| EP2248421A1 (en) | 2009-05-07 | 2010-11-10 | GMI - Gregor-Mendel-Institut für Molekulare Pflanzenbiologie GmbH | Accumulation of biomass in plants |
| FI20106119A0 (fi) | 2010-10-27 | 2010-10-27 | Sirtuin Valley Oy | Energia-aineenvaihduntaan vaikuttava koostumus |
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- 2012-09-20 IN IN2680CHN2014 patent/IN2014CN02680A/en unknown
- 2012-09-20 JP JP2014531375A patent/JP2014527979A/ja active Pending
- 2012-09-20 EP EP12833721.9A patent/EP2758392B1/en not_active Not-in-force
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005077177A2 (fr) * | 2004-02-10 | 2005-08-25 | Universite Paul Sabatier Toulouse Iii | Modulateurs de developpement des champignons mycorhiziens a arbuscules, et applications |
| JP2010529975A (ja) * | 2007-06-15 | 2010-09-02 | バイエル・クロツプサイエンス・エス・アー | ストリゴラクトン誘導体と殺菌剤化合物を含んでいる殺有害生物剤組成物 |
Non-Patent Citations (3)
| Title |
|---|
| JPN6016018937; Eur. J. Org. Chem, 2011 Jul, Vol.2011, p.3781-3793 * |
| JPN6016018941; ACS Symp. ser., 1991, Vol.443, p.278-287 * |
| JPN6016018944; J.C.S. Chem. Comm., 1974, Vol.13, p.512-513 * |
Also Published As
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|---|---|
| CA2849343A1 (en) | 2013-03-28 |
| CN104053655A (zh) | 2014-09-17 |
| US10208007B2 (en) | 2019-02-19 |
| EP2758392B1 (en) | 2019-09-18 |
| EP2758392A4 (en) | 2015-05-20 |
| EP2758392A1 (en) | 2014-07-30 |
| US20140323563A1 (en) | 2014-10-30 |
| CA2849343C (en) | 2020-12-15 |
| WO2013042124A8 (en) | 2013-07-25 |
| WO2013042124A1 (en) | 2013-03-28 |
| IN2014CN02680A (cg-RX-API-DMAC7.html) | 2015-07-03 |
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