UA75691C2 - Quinoline derivatives, use thereof as antitumor drugs, composition based thereon and therapeutical method for treatment of cancer - Google Patents
Quinoline derivatives, use thereof as antitumor drugs, composition based thereon and therapeutical method for treatment of cancer Download PDFInfo
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- UA75691C2 UA75691C2 UA2004021374A UA2004021374A UA75691C2 UA 75691 C2 UA75691 C2 UA 75691C2 UA 2004021374 A UA2004021374 A UA 2004021374A UA 2004021374 A UA2004021374 A UA 2004021374A UA 75691 C2 UA75691 C2 UA 75691C2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/227—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US30914401P | 2001-07-31 | 2001-07-31 | |
PCT/US2002/024442 WO2003011832A1 (en) | 2001-07-31 | 2002-07-31 | Quinoline derivatives and use thereof as antitumor agents |
Publications (1)
Publication Number | Publication Date |
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UA75691C2 true UA75691C2 (en) | 2006-05-15 |
Family
ID=23196886
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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UA2004021374A UA75691C2 (en) | 2001-07-31 | 2002-07-31 | Quinoline derivatives, use thereof as antitumor drugs, composition based thereon and therapeutical method for treatment of cancer |
Country Status (22)
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US (3) | US6867219B2 (no) |
EP (1) | EP1412332B1 (no) |
JP (1) | JP4310185B2 (no) |
KR (1) | KR20040055774A (no) |
AT (1) | ATE287397T1 (no) |
AU (1) | AU2002355747B2 (no) |
CA (1) | CA2456173A1 (no) |
DE (1) | DE60202682T2 (no) |
DK (1) | DK1412332T3 (no) |
EA (1) | EA007205B1 (no) |
ES (1) | ES2236548T3 (no) |
GE (1) | GEP20063754B (no) |
HU (1) | HUP0401562A2 (no) |
IL (2) | IL160082A0 (no) |
MX (1) | MXPA04000968A (no) |
NO (1) | NO326463B1 (no) |
NZ (1) | NZ530806A (no) |
PL (1) | PL367340A1 (no) |
PT (1) | PT1412332E (no) |
UA (1) | UA75691C2 (no) |
WO (1) | WO2003011832A1 (no) |
ZA (1) | ZA200401185B (no) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
RU2446159C2 (ru) * | 2006-12-06 | 2012-03-27 | Янссен Фармацевтика Н.В. | Антибактериальные производные хинолина |
Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE60115394T2 (de) * | 2000-02-29 | 2006-10-19 | Millennium Pharmaceuticals, Inc., Cambridge | Benzamide und ähnliche inhibitoren vom faktor xa |
PL367340A1 (en) * | 2001-07-31 | 2005-02-21 | Wayne State University | Quinoline derivatives and use thereof as antitumor agents |
UA79293C2 (en) * | 2002-07-03 | 2007-06-11 | Univ Wayne State | 4-(7'-halo-2-quino (xa-) linyloxy)phenoxy propionic acid derivatives as antineoplastic agents |
RU2322236C2 (ru) * | 2002-08-24 | 2008-04-20 | Центарис Гмбх | Лекарственное средство для лечения доброкачественных и злокачественных опухолевых заболеваний, содержащее производное дисоразола |
US8183379B2 (en) | 2005-09-07 | 2012-05-22 | Wayne State University | Antitumor agents |
US20070054938A1 (en) * | 2005-09-07 | 2007-03-08 | Horwitz Jerome P | Antitumor agents |
US7470788B2 (en) | 2005-09-07 | 2008-12-30 | Wayne State University | Antitumor agents |
EP1897542A1 (en) * | 2006-09-07 | 2008-03-12 | Sanofi-Aventis | Aqueous formulation comprising an antitumor agent |
WO2009002955A1 (en) * | 2007-06-27 | 2008-12-31 | Sanofi-Aventis U.S. Llc | Process for the preparation of (2r)-2-[4-(7-bromo-2-quinolyloxy)phenoxy]propanoic acid |
US8809562B2 (en) | 2011-06-06 | 2014-08-19 | Chevron Phillips Chemical Company Lp | Use of metallocene compounds for cancer treatment |
WO2024132001A1 (en) * | 2022-12-21 | 2024-06-27 | Charles University, Faculty Of Pharmacy In Hradec Kralove | Multitarget nuclear receptor ligands based on 2-(4-(quinolin-2-yloxy)phenoxy)propanoic acid and 2-(4-(quinoxalin-2-yloxy)phenoxy)propanoic acid for the treatment of metabolic and liver diseases |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS6033389B2 (ja) * | 1979-02-22 | 1985-08-02 | 日産化学工業株式会社 | 複素環エ−テル系フェノシキ脂肪酸誘導体、その製造法および該誘導体を含有する除草剤 |
US6197728B1 (en) | 1980-08-06 | 2001-03-06 | Nissan Chemical Industries Ltd. | Quinoxaline derivatives and herbicidal composition |
US5364831A (en) | 1980-08-06 | 1994-11-15 | Nissan Chemical Industries Ltd. | Quinoxaline derivatives and herbicidal composition |
US5250690A (en) * | 1985-05-02 | 1993-10-05 | Dowelanco | Haloalkoxy anilide derivatives of 2-4(-heterocyclic oxyphenoxy)alkanoic or alkenoic acids and their use as herbicides |
PL367340A1 (en) * | 2001-07-31 | 2005-02-21 | Wayne State University | Quinoline derivatives and use thereof as antitumor agents |
UA79293C2 (en) * | 2002-07-03 | 2007-06-11 | Univ Wayne State | 4-(7'-halo-2-quino (xa-) linyloxy)phenoxy propionic acid derivatives as antineoplastic agents |
US7470788B2 (en) * | 2005-09-07 | 2008-12-30 | Wayne State University | Antitumor agents |
-
2002
- 2002-07-31 PL PL02367340A patent/PL367340A1/xx not_active Application Discontinuation
- 2002-07-31 NZ NZ530806A patent/NZ530806A/en unknown
- 2002-07-31 DE DE60202682T patent/DE60202682T2/de not_active Expired - Lifetime
- 2002-07-31 EA EA200400219A patent/EA007205B1/ru not_active IP Right Cessation
- 2002-07-31 IL IL16008202A patent/IL160082A0/xx unknown
- 2002-07-31 MX MXPA04000968A patent/MXPA04000968A/es active IP Right Grant
- 2002-07-31 DK DK02752656T patent/DK1412332T3/da active
- 2002-07-31 CA CA002456173A patent/CA2456173A1/en not_active Abandoned
- 2002-07-31 AT AT02752656T patent/ATE287397T1/de not_active IP Right Cessation
- 2002-07-31 WO PCT/US2002/024442 patent/WO2003011832A1/en active IP Right Grant
- 2002-07-31 PT PT02752656T patent/PT1412332E/pt unknown
- 2002-07-31 HU HU0401562A patent/HUP0401562A2/hu unknown
- 2002-07-31 ES ES02752656T patent/ES2236548T3/es not_active Expired - Lifetime
- 2002-07-31 JP JP2003517024A patent/JP4310185B2/ja not_active Expired - Fee Related
- 2002-07-31 GE GE5486A patent/GEP20063754B/en unknown
- 2002-07-31 EP EP02752656A patent/EP1412332B1/en not_active Expired - Lifetime
- 2002-07-31 AU AU2002355747A patent/AU2002355747B2/en not_active Ceased
- 2002-07-31 UA UA2004021374A patent/UA75691C2/uk unknown
- 2002-07-31 US US10/210,781 patent/US6867219B2/en not_active Expired - Lifetime
- 2002-07-31 KR KR10-2004-7001559A patent/KR20040055774A/ko active IP Right Grant
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2004
- 2004-01-27 IL IL160082A patent/IL160082A/en not_active IP Right Cessation
- 2004-01-28 NO NO20040382A patent/NO326463B1/no not_active IP Right Cessation
- 2004-02-13 ZA ZA200401185A patent/ZA200401185B/en unknown
- 2004-12-10 US US11/009,457 patent/US7241894B2/en not_active Expired - Fee Related
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
RU2446159C2 (ru) * | 2006-12-06 | 2012-03-27 | Янссен Фармацевтика Н.В. | Антибактериальные производные хинолина |
Also Published As
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GEP20063754B (en) | 2006-02-27 |
DE60202682D1 (de) | 2005-02-24 |
ATE287397T1 (de) | 2005-02-15 |
JP4310185B2 (ja) | 2009-08-05 |
US20050159447A1 (en) | 2005-07-21 |
AU2002355747B2 (en) | 2007-12-20 |
NO326463B1 (no) | 2008-12-08 |
US6867219B2 (en) | 2005-03-15 |
PL367340A1 (en) | 2005-02-21 |
US7241894B2 (en) | 2007-07-10 |
EP1412332B1 (en) | 2005-01-19 |
EA007205B1 (ru) | 2006-08-25 |
US20070232643A1 (en) | 2007-10-04 |
HUP0401562A2 (hu) | 2004-12-28 |
IL160082A0 (en) | 2004-06-20 |
NZ530806A (en) | 2006-05-26 |
WO2003011832A1 (en) | 2003-02-13 |
KR20040055774A (ko) | 2004-06-26 |
CA2456173A1 (en) | 2003-02-13 |
JP2004538314A (ja) | 2004-12-24 |
US20030144321A1 (en) | 2003-07-31 |
IL160082A (en) | 2009-06-15 |
DK1412332T3 (da) | 2005-05-30 |
ES2236548T3 (es) | 2005-07-16 |
EP1412332A1 (en) | 2004-04-28 |
MXPA04000968A (es) | 2005-02-17 |
DE60202682T2 (de) | 2005-12-29 |
US7507749B2 (en) | 2009-03-24 |
NO20040382L (no) | 2004-03-26 |
ZA200401185B (en) | 2004-10-21 |
EA200400219A1 (ru) | 2004-12-30 |
PT1412332E (pt) | 2005-06-30 |
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