IL141248A0 - Substituted oxazole and thiazole derivatives as hppar gamma and hppar alpha activators - Google Patents
Substituted oxazole and thiazole derivatives as hppar gamma and hppar alpha activatorsInfo
- Publication number
- IL141248A0 IL141248A0 IL14124899A IL14124899A IL141248A0 IL 141248 A0 IL141248 A0 IL 141248A0 IL 14124899 A IL14124899 A IL 14124899A IL 14124899 A IL14124899 A IL 14124899A IL 141248 A0 IL141248 A0 IL 141248A0
- Authority
- IL
- Israel
- Prior art keywords
- hppar
- gamma
- thiazole derivatives
- substituted oxazole
- alpha activators
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/24—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Child & Adolescent Psychology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9817118.4A GB9817118D0 (en) | 1998-08-07 | 1998-08-07 | Pharmaceutical compounds |
| PCT/EP1999/005666 WO2000008002A1 (en) | 1998-08-07 | 1999-08-05 | SUBSTITUTED OXAZOLES AND THIAZOLES DERIVATIVES AS hPPAR GAMMA AND hPPAR ALPHA ACTIVATORS |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| IL141248A0 true IL141248A0 (en) | 2002-03-10 |
Family
ID=10836805
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL14124899A IL141248A0 (en) | 1998-08-07 | 1999-08-05 | Substituted oxazole and thiazole derivatives as hppar gamma and hppar alpha activators |
Country Status (31)
| Country | Link |
|---|---|
| US (1) | US6498174B1 (xx) |
| EP (1) | EP1102757B1 (xx) |
| JP (1) | JP2002522426A (xx) |
| KR (1) | KR20010085340A (xx) |
| CN (1) | CN1321152A (xx) |
| AP (1) | AP2001002066A0 (xx) |
| AR (1) | AR020001A1 (xx) |
| AT (1) | ATE264313T1 (xx) |
| AU (1) | AU5731099A (xx) |
| BR (1) | BR9912866A (xx) |
| CA (1) | CA2339773A1 (xx) |
| CO (1) | CO5070570A1 (xx) |
| CZ (1) | CZ2001490A3 (xx) |
| DE (1) | DE69916457T2 (xx) |
| EA (1) | EA200100105A1 (xx) |
| EE (1) | EE200100074A (xx) |
| ES (1) | ES2220110T3 (xx) |
| GB (1) | GB9817118D0 (xx) |
| HR (1) | HRP20010095A2 (xx) |
| HU (1) | HUP0103469A3 (xx) |
| ID (1) | ID29543A (xx) |
| IL (1) | IL141248A0 (xx) |
| IS (1) | IS5840A (xx) |
| MA (1) | MA26668A1 (xx) |
| NO (1) | NO20010628L (xx) |
| PE (1) | PE20000947A1 (xx) |
| PL (1) | PL345882A1 (xx) |
| SK (1) | SK1962001A3 (xx) |
| TR (1) | TR200100372T2 (xx) |
| WO (1) | WO2000008002A1 (xx) |
| ZA (1) | ZA200100983B (xx) |
Families Citing this family (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6417212B1 (en) | 1999-08-27 | 2002-07-09 | Eli Lilly & Company | Modulators of peroxisome proliferator activated receptors |
| EP1589006A1 (en) * | 1999-09-22 | 2005-10-26 | Bristol-Myers Squibb Company | Oxa- and thiazole derivatives useful as antidiabetics and antidiobesity agents |
| TW200514783A (en) * | 1999-09-22 | 2005-05-01 | Bristol Myers Squibb Co | Substituted acid derivatives useful as antiodiabetic and antiobesity agents and method |
| US6414002B1 (en) | 1999-09-22 | 2002-07-02 | Bristol-Myers Squibb Company | Substituted acid derivatives useful as antidiabetic and antiobesity agents and method |
| GB0002667D0 (en) * | 2000-02-04 | 2000-03-29 | Glaxo Group Ltd | medicamesnts |
| GB0031103D0 (en) * | 2000-12-20 | 2001-01-31 | Glaxo Group Ltd | Chemical compounds |
| US20040072838A1 (en) | 2000-12-20 | 2004-04-15 | Pierette Banker | Thiazole and oxazole derivatives as activators of human peroxisome proliferator activated receptors |
| US7241785B2 (en) | 2001-03-23 | 2007-07-10 | Takeda Pharmaceutical Company Limited | Five-membered heterocyclic alkanoic acid derivative |
| GB0111523D0 (en) | 2001-05-11 | 2001-07-04 | Glaxo Group Ltd | Chemical compounds |
| IL158589A0 (en) * | 2001-05-15 | 2004-05-12 | Hoffmann La Roche | Carboxylic acid substituted oxazole derivatives for use as ppar-alpha and -gamma activators in the treatment of diabetes |
| AU2002308891B2 (en) * | 2001-05-29 | 2007-09-06 | Kyoto Pharmaceutical Industries, Ltd. | Novel heterocyclic derivatives and medicinal use thereof |
| MXPA03010811A (es) * | 2001-05-29 | 2004-02-27 | Kyoto Pharma Ind | Compuestos heterociclico y uso farmaceutico. |
| US6861440B2 (en) | 2001-10-26 | 2005-03-01 | Hoffmann-La Roche Inc. | DPP IV inhibitors |
| TW200300681A (en) | 2001-11-12 | 2003-06-16 | Ono Pharmaceutical Co | Carboxylic acid derivative compound and medicament containing same as active ingredient |
| JP3884736B2 (ja) * | 2002-01-17 | 2007-02-21 | トーアエイヨー株式会社 | ハロゲノベンジルアミノプロピオン酸誘導体 |
| US6716842B2 (en) | 2002-04-05 | 2004-04-06 | Warner-Lambert Company, Llc | Antidiabetic agents |
| US20050119314A1 (en) * | 2002-04-05 | 2005-06-02 | Sankyo Company, Limited | Pharmaceutical composition comprising an ACAT inhibitor and an insulin resistance reducing agent |
| KR100474202B1 (ko) * | 2002-05-04 | 2005-03-08 | 강헌중 | 티아졸 유도체의 제조방법 및 이를 제조하기 위한 중간체 |
| KR100621294B1 (ko) | 2002-07-03 | 2006-09-06 | 에프. 호프만-라 로슈 아게 | 옥사졸 유도체 및 이의 인슐린 증감제로서의 용도 |
| PL374860A1 (en) | 2002-07-09 | 2005-11-14 | Bristol-Myers Squibb Company | Substituted heterocyclic derivatives useful as antidiabetic and antiobesity agents and method |
| EP1537091B1 (en) * | 2002-08-30 | 2010-10-06 | F. Hoffmann-La Roche AG | Novel 2-arylthiazole compounds as pparalpha and ppargamma agonists |
| RU2296759C2 (ru) | 2002-09-12 | 2007-04-10 | Ф.Хоффманн-Ля Рош Аг | N-замещенные 1н-индол-5-пропионовые кислоты, фармацевтическая композиция, содержащая эти соединения, и их применение (варианты) |
| AR041481A1 (es) * | 2002-10-07 | 2005-05-18 | Hoffmann La Roche | Derivados de acido arilpropionico-oxazol y su uso como agonistas de ppar |
| MXPA05005445A (es) | 2002-11-25 | 2005-08-26 | Hoffmann La Roche | Derivados de indolilo. |
| US7268157B2 (en) * | 2002-11-26 | 2007-09-11 | Shenzhen Chipscreen Biosciences, Ltd. | Substituted arylalcanoic acid derivatives as PPAR pan agonists with potent antihyperglycemic and antihyperlipidemic activity |
| US7192970B2 (en) | 2002-11-26 | 2007-03-20 | Chipscreen Biosciences, Ltd. | Noncyclic 1,3-dicarbonyl compounds as dual PPAR agonists with potent antihyperglycemic and antihyperlipidemic activity |
| RS52397B (en) | 2003-06-20 | 2013-02-28 | F.Hoffmann-La Roche Ag | PYRIDO / 2,1-A / ISOCHINOLINE DERIVATIVES AS DPP-IV INHIBITORS |
| KR100744893B1 (ko) | 2003-06-20 | 2007-08-01 | 에프. 호프만-라 로슈 아게 | Ｄｐｐ-ｉｖ 저해제로서 헥사하이드로피리도아이소퀴놀린 |
| EP1742904B1 (en) | 2004-05-06 | 2012-10-31 | The Regents of The University of California | Substituted enaminones, their derivatives and uses thereof |
| CN100436430C (zh) * | 2004-05-24 | 2008-11-26 | 北京摩力克科技有限公司 | 作为hPPARα和hPPARγ激动剂的烷酰基取代的酪氨酸衍生物 |
| CN100467456C (zh) * | 2004-05-24 | 2009-03-11 | 北京摩力克科技有限公司 | 作为hPPARα和/或hPPARγ激活剂的α-哌嗪取代的苯丙酸衍生物 |
| CN100344618C (zh) | 2004-05-24 | 2007-10-24 | 北京摩力克科技有限公司 | 作为hPPARα和hPPARγ激动剂的N－芳丙烯酰基取代的酪氨酸衍生物 |
| CN1896069B (zh) * | 2005-07-15 | 2011-10-05 | 中国科学院上海药物研究所 | 一类取代噻唑-4酮化合物、制备方法和用途 |
| CN101007790B (zh) * | 2006-01-27 | 2011-03-30 | 北京摩力克科技有限公司 | 草氨酸衍生物、其制备方法和医药用途 |
| EP2030974B1 (en) * | 2006-06-13 | 2016-02-17 | Shanghai Institute of Materia Medica, Chinese Academy of Sciences | Thiazole non-nucleoside compounds, their preparation, pharmaceutical composition and their use as antiviral agents |
| GB0719180D0 (en) * | 2007-10-02 | 2007-11-14 | Cambrex Karlskoga Ab | New process |
| EP2135865A1 (de) | 2008-06-17 | 2009-12-23 | Bayer CropScience AG | Substituierte 1-(Diazinyl) pyrazol-4-yl-essigsäuren, Verfahren zu deren Herstellung und deren Verwendung als Herbizide und Pflanzenwachstumsregulatoren |
| EP2194052A1 (de) | 2008-12-06 | 2010-06-09 | Bayer CropScience AG | Substituierte 1-(Thiazolyl)- und 1-(Isothiazolyl)pyrazol-4-yl-essigsäuren, Verfahren zu deren Herstellung und deren Verwendung als Herbizide und Pflanzenwachstumsregulatoren |
| WO2011073098A1 (de) | 2009-12-15 | 2011-06-23 | Bayer Cropscience Ag | 1-(heteroaryl)-pyrazol-4-yl-essigsäuren, verfahren zu deren herstellung und deren verwendung als herbizide und pflanzenwachstumsregulatoren |
| US20120094959A1 (en) | 2010-10-19 | 2012-04-19 | Bonnie Blazer-Yost | Treatment of cystic diseases |
| WO2022052982A1 (zh) * | 2020-09-14 | 2022-03-17 | 昭明泽康（北京）生物医药科技有限公司 | PPARα（过氧化物酶体增殖物激活受体α）配体在制备药物中的应用 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5089514A (en) | 1990-06-14 | 1992-02-18 | Pfizer Inc. | 3-coxazolyl [phenyl, chromanyl or benzofuranyl]-2-hydroxypropionic acid derivatives and analogs as hypoglycemic agents |
| US6062509A (en) | 1994-12-23 | 2000-05-16 | Hexcel Corporation | Retrofit centerline luggage bin assemblies compatible with existing aircraft bin supports |
| JPH08325263A (ja) | 1995-05-31 | 1996-12-10 | Sumitomo Metal Ind Ltd | 新規２−アミノ−３−フェニルプロピオン酸誘導体 |
| GB9604242D0 (en) * | 1996-02-28 | 1996-05-01 | Glaxo Wellcome Inc | Chemical compounds |
| CZ53699A3 (cs) * | 1996-08-19 | 1999-07-14 | Japan Tobacco Inc. | Deriváty propionové kyseliny a jejich použití |
-
1998
- 1998-08-07 GB GBGB9817118.4A patent/GB9817118D0/en not_active Ceased
-
1999
- 1999-08-04 AR ARP990103874A patent/AR020001A1/es not_active Application Discontinuation
- 1999-08-04 CO CO99049333A patent/CO5070570A1/es unknown
- 1999-08-05 ES ES99944335T patent/ES2220110T3/es not_active Expired - Lifetime
- 1999-08-05 EP EP99944335A patent/EP1102757B1/en not_active Expired - Lifetime
- 1999-08-05 US US09/762,445 patent/US6498174B1/en not_active Expired - Fee Related
- 1999-08-05 AT AT99944335T patent/ATE264313T1/de not_active IP Right Cessation
- 1999-08-05 EE EEP200100074A patent/EE200100074A/xx unknown
- 1999-08-05 EA EA200100105A patent/EA200100105A1/ru unknown
- 1999-08-05 MA MA25716A patent/MA26668A1/fr unknown
- 1999-08-05 ID IDW20010541A patent/ID29543A/id unknown
- 1999-08-05 IL IL14124899A patent/IL141248A0/xx unknown
- 1999-08-05 PE PE1999000790A patent/PE20000947A1/es not_active Application Discontinuation
- 1999-08-05 TR TR2001/00372T patent/TR200100372T2/xx unknown
- 1999-08-05 HU HU0103469A patent/HUP0103469A3/hu unknown
- 1999-08-05 PL PL99345882A patent/PL345882A1/xx not_active Application Discontinuation
- 1999-08-05 CA CA002339773A patent/CA2339773A1/en not_active Abandoned
- 1999-08-05 DE DE69916457T patent/DE69916457T2/de not_active Expired - Lifetime
- 1999-08-05 CN CN99811640A patent/CN1321152A/zh active Pending
- 1999-08-05 JP JP2000563635A patent/JP2002522426A/ja active Pending
- 1999-08-05 CZ CZ2001490A patent/CZ2001490A3/cs unknown
- 1999-08-05 BR BR9912866-7A patent/BR9912866A/pt not_active Application Discontinuation
- 1999-08-05 AU AU57310/99A patent/AU5731099A/en not_active Abandoned
- 1999-08-05 KR KR1020017001617A patent/KR20010085340A/ko not_active Application Discontinuation
- 1999-08-05 SK SK196-2001A patent/SK1962001A3/sk unknown
- 1999-08-05 AP APAP/P/2001/002066A patent/AP2001002066A0/en unknown
- 1999-08-05 WO PCT/EP1999/005666 patent/WO2000008002A1/en not_active Application Discontinuation
-
2001
- 2001-02-05 IS IS5840A patent/IS5840A/is unknown
- 2001-02-05 ZA ZA200100983A patent/ZA200100983B/en unknown
- 2001-02-06 NO NO20010628A patent/NO20010628L/no not_active Application Discontinuation
- 2001-02-07 HR HR20010095A patent/HRP20010095A2/hr not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| ID29543A (id) | 2001-09-06 |
| DE69916457D1 (de) | 2004-05-19 |
| AR020001A1 (es) | 2002-03-27 |
| CZ2001490A3 (cs) | 2001-08-15 |
| NO20010628L (no) | 2001-04-06 |
| GB9817118D0 (en) | 1998-10-07 |
| CO5070570A1 (es) | 2001-08-28 |
| JP2002522426A (ja) | 2002-07-23 |
| PL345882A1 (en) | 2002-01-14 |
| EA200100105A1 (ru) | 2001-08-27 |
| PE20000947A1 (es) | 2000-09-22 |
| MA26668A1 (fr) | 2004-12-20 |
| ES2220110T3 (es) | 2004-12-01 |
| WO2000008002A1 (en) | 2000-02-17 |
| EE200100074A (et) | 2002-06-17 |
| EP1102757B1 (en) | 2004-04-14 |
| HUP0103469A3 (en) | 2002-08-28 |
| US6498174B1 (en) | 2002-12-24 |
| TR200100372T2 (tr) | 2001-09-21 |
| HUP0103469A2 (hu) | 2002-01-28 |
| DE69916457T2 (de) | 2005-04-14 |
| NO20010628D0 (no) | 2001-02-06 |
| KR20010085340A (ko) | 2001-09-07 |
| AU5731099A (en) | 2000-02-28 |
| BR9912866A (pt) | 2001-10-30 |
| AP2001002066A0 (en) | 2001-03-31 |
| CN1321152A (zh) | 2001-11-07 |
| ATE264313T1 (de) | 2004-04-15 |
| EP1102757A1 (en) | 2001-05-30 |
| ZA200100983B (en) | 2002-03-05 |
| HRP20010095A2 (en) | 2002-02-28 |
| CA2339773A1 (en) | 2000-02-17 |
| SK1962001A3 (en) | 2001-11-06 |
| IS5840A (is) | 2001-02-05 |
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| IL115269A (en) | Heterocyclic intermediate compounds for use in the preparation of oxazolidinedione and thiazolidinedione derivatives | |
| SI1089998T1 (sl) | Derivati epotilona, njihova sinteza in uporaba |