SI21099A - N-(5-(((5-alkil-2-oksazolil)metil)tio)-2-tiazolil) karboksamidni inhibitorji ciklin odvisnih kinaz - Google Patents
N-(5-(((5-alkil-2-oksazolil)metil)tio)-2-tiazolil) karboksamidni inhibitorji ciklin odvisnih kinaz Download PDFInfo
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- SI21099A SI21099A SI200120051A SI200120051A SI21099A SI 21099 A SI21099 A SI 21099A SI 200120051 A SI200120051 A SI 200120051A SI 200120051 A SI200120051 A SI 200120051A SI 21099 A SI21099 A SI 21099A
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- Slovenia
- Prior art keywords
- citrate
- hydrochloride
- trifluoroacetate
- pharmaceutically acceptable
- compound
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Classifications
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- 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
- C07D417/14—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 three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
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- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Dermatology (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US61662700A | 2000-07-26 | 2000-07-26 | |
| US09/727,957 US6515004B1 (en) | 1999-12-15 | 2000-12-01 | N-[5-[[[5-alkyl-2-oxazolyl]methyl]thio]-2-thiazolyl]-carboxamide inhibitors of cyclin dependent kinases |
| US09/746,060 US6414156B2 (en) | 1998-10-21 | 2000-12-22 | Process for preparing azacycloalkanoylaminothiazoles |
| PCT/US2001/015081 WO2002010162A1 (en) | 2000-07-26 | 2001-05-09 | N-[5-[[[5-alkyl-2-oxazolyl]methyl]thio]-2-thiazolyl] carboxamide inhibitors of cyclin dependent kinases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SI21099A true SI21099A (sl) | 2003-06-30 |
Family
ID=27417184
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SI200120051A SI21099A (sl) | 2000-07-26 | 2001-05-09 | N-(5-(((5-alkil-2-oksazolil)metil)tio)-2-tiazolil) karboksamidni inhibitorji ciklin odvisnih kinaz |
Country Status (26)
| Country | Link |
|---|---|
| EP (1) | EP1303513A1 (https=) |
| JP (1) | JP2004509857A (https=) |
| KR (1) | KR20030016429A (https=) |
| CN (1) | CN100457753C (https=) |
| AR (1) | AR030563A1 (https=) |
| AU (1) | AU2001259704A1 (https=) |
| BG (1) | BG65132B1 (https=) |
| BR (1) | BR0112674A (https=) |
| CA (1) | CA2417254A1 (https=) |
| CZ (1) | CZ2003237A3 (https=) |
| EE (1) | EE200300041A (https=) |
| EG (1) | EG24409A (https=) |
| GE (1) | GEP20043367B (https=) |
| HR (1) | HRP20030116A2 (https=) |
| HU (1) | HUP0303698A2 (https=) |
| IL (2) | IL153591A0 (https=) |
| LV (1) | LV13037B (https=) |
| MX (1) | MXPA03000774A (https=) |
| MY (1) | MY129635A (https=) |
| NO (1) | NO20030394L (https=) |
| PL (1) | PL365170A1 (https=) |
| SI (1) | SI21099A (https=) |
| SK (1) | SK18392002A3 (https=) |
| TW (1) | TWI302533B (https=) |
| WO (1) | WO2002010162A1 (https=) |
| YU (1) | YU4903A (https=) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6414156B2 (en) | 1998-10-21 | 2002-07-02 | Bristol-Myers Squibb Company | Process for preparing azacycloalkanoylaminothiazoles |
| EP2311818B1 (en) * | 2002-02-28 | 2013-01-16 | Novartis AG | Combination of a 5-phenylthiazole compound as PI3 kinase inhibitor with an antiinflammatory, bronchodilatory or antihistamine drug |
| TWI314928B (en) | 2002-02-28 | 2009-09-21 | Novartis A | 5-phenylthiazole derivatives and use as pi3 kinase inhibitors |
| NZ539163A (en) | 2002-09-04 | 2007-03-30 | Schering Corp | Pyrazolo[1,5-a]pyrimidine compounds useful as cyclin dependent kinase (CDK) inhibitors |
| PT1537116E (pt) | 2002-09-04 | 2010-09-03 | Schering Corp | Pirazolopirimidinas adequadas para o tratamento de doenças cancerosas |
| US8580782B2 (en) | 2002-09-04 | 2013-11-12 | Merck Sharp & Dohme Corp. | Substituted pyrazolo[1,5-a]pyrimidines as cyclin dependent kinase inhibitors |
| US8673924B2 (en) | 2002-09-04 | 2014-03-18 | Merck Sharp & Dohme Corp. | Substituted pyrazolo[1,5-a]pyrimidines as cyclin dependent kinase inhibitors |
| US7186740B2 (en) | 2002-09-23 | 2007-03-06 | Schering Corporation | Imidazopyrazines as cyclin dependent kinase inhibitors |
| TW200413378A (en) | 2002-09-23 | 2004-08-01 | Schering Corp | Novel imidazopyrazines as cyclin dependent kinase inhibitors |
| GB0320197D0 (en) * | 2003-08-28 | 2003-10-01 | Novartis Ag | Organic compounds |
| EP1555264A1 (en) * | 2004-01-15 | 2005-07-20 | Sireen AG | Five-membered heterocyclic compounds as inhibitors of SRC family protein kinase. |
| DE102005008310A1 (de) * | 2005-02-17 | 2006-08-24 | Schering Ag | Verwendung von CDKII Inhibitoren zur Fertilitätskontrolle |
| CN101287728A (zh) * | 2005-08-17 | 2008-10-15 | 先灵公司 | 新的高亲和力噻吩基和呋喃基激酶配体 |
| CA2621983A1 (en) | 2005-09-09 | 2007-03-22 | Schering Corporation | Azafused cyclin dependent kinase inhibitors |
| CN101321760A (zh) | 2005-10-06 | 2008-12-10 | 先灵公司 | 作为蛋白激酶抑制剂的吡唑并嘧啶 |
| US20090175852A1 (en) | 2006-06-06 | 2009-07-09 | Schering Corporation | Imidazopyrazines as protein kinase inhibitors |
| WO2007146039A2 (en) * | 2006-06-06 | 2007-12-21 | Bristol-Myers Squibb Company | Crystalline forms of n-[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl] thio]-2-thiazolyl]-4-piperidinecarboxamide |
| AR063531A1 (es) | 2006-10-31 | 2009-01-28 | Schering Corp | Derivados de anilinopiperazina y composicion farmaceutica |
| CA2668210C (en) | 2006-10-31 | 2013-03-12 | Schering Corporation | Anilinopiperazine derivatives and methods of use thereof |
| EP2409700A1 (en) | 2007-05-08 | 2012-01-25 | Schering Corporation | Methods of treatment using intravenous formulations comprising temozolomide |
| TW200922564A (en) | 2007-09-10 | 2009-06-01 | Curis Inc | CDK inhibitors containing a zinc binding moiety |
| WO2010075542A1 (en) | 2008-12-23 | 2010-07-01 | Curis, Inc. | Cdk inhibitors |
| WO2011025706A2 (en) | 2009-08-26 | 2011-03-03 | Schering Corporation | Heterocyclic amide compounds as protein kinase inhibitors |
| WO2013148775A1 (en) | 2012-03-30 | 2013-10-03 | Merck Sharp & Dohme Corp. | Predictive biomarker useful for cancer therapy mediated by a cdk inhibitor |
| JP6212831B2 (ja) * | 2013-12-04 | 2017-10-18 | 杭州源昶医薬科技有限公司 | ゲムシタビン誘導体、該誘導体を含む組成物及び該誘導体の製薬用途 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6262096B1 (en) * | 1997-11-12 | 2001-07-17 | Bristol-Myers Squibb Company | Aminothiazole inhibitors of cyclin dependent kinases |
| US6040321A (en) * | 1997-11-12 | 2000-03-21 | Bristol-Myers Squibb Company | Aminothiazole inhibitors of cyclin dependent kinases |
| CA2332325A1 (en) * | 1998-06-18 | 1999-12-23 | Bristol-Myers Squibb Company | Carbon substituted aminothiazole inhibitors of cyclin dependent kinases |
| US6414156B2 (en) * | 1998-10-21 | 2002-07-02 | Bristol-Myers Squibb Company | Process for preparing azacycloalkanoylaminothiazoles |
| MY125768A (en) * | 1999-12-15 | 2006-08-30 | Bristol Myers Squibb Co | N-[5-[[[5-alkyl-2-oxazolyl]methyl]thio]-2-thiazolyl]-carboxamide inhibitors of cyclin dependent kinases |
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2001
- 2001-05-09 PL PL01365170A patent/PL365170A1/xx not_active Application Discontinuation
- 2001-05-09 YU YU4903A patent/YU4903A/sh unknown
- 2001-05-09 SK SK1839-2002A patent/SK18392002A3/sk unknown
- 2001-05-09 CA CA002417254A patent/CA2417254A1/en not_active Abandoned
- 2001-05-09 GE GE5063A patent/GEP20043367B/en unknown
- 2001-05-09 CN CNB018133673A patent/CN100457753C/zh not_active Expired - Fee Related
- 2001-05-09 SI SI200120051A patent/SI21099A/sl not_active IP Right Cessation
- 2001-05-09 BR BR0112674-1A patent/BR0112674A/pt not_active Application Discontinuation
- 2001-05-09 WO PCT/US2001/015081 patent/WO2002010162A1/en not_active Ceased
- 2001-05-09 IL IL15359101A patent/IL153591A0/xx unknown
- 2001-05-09 MX MXPA03000774A patent/MXPA03000774A/es unknown
- 2001-05-09 EP EP01933266A patent/EP1303513A1/en not_active Withdrawn
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- 2001-05-09 JP JP2002515891A patent/JP2004509857A/ja not_active Withdrawn
- 2001-05-09 HU HU0303698A patent/HUP0303698A2/hu unknown
- 2001-05-09 CZ CZ2003237A patent/CZ2003237A3/cs unknown
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- 2001-05-09 AU AU2001259704A patent/AU2001259704A1/en not_active Abandoned
- 2001-05-16 TW TW090111741A patent/TWI302533B/zh not_active IP Right Cessation
- 2001-05-22 MY MYPI20012414A patent/MY129635A/en unknown
- 2001-05-23 EG EG20010550A patent/EG24409A/xx active
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Also Published As
| Publication number | Publication date |
|---|---|
| PL365170A1 (en) | 2004-12-27 |
| WO2002010162A1 (en) | 2002-02-07 |
| TWI302533B (en) | 2008-11-01 |
| SK18392002A3 (sk) | 2003-09-11 |
| YU4903A (sh) | 2006-03-03 |
| HUP0303698A2 (hu) | 2004-04-28 |
| IL153591A0 (en) | 2003-07-06 |
| CN100457753C (zh) | 2009-02-04 |
| EG24409A (en) | 2009-05-20 |
| EP1303513A1 (en) | 2003-04-23 |
| GEP20043367B (en) | 2004-06-10 |
| EE200300041A (et) | 2005-04-15 |
| NO20030394D0 (no) | 2003-01-24 |
| NO20030394L (no) | 2003-03-03 |
| IL153591A (en) | 2009-07-20 |
| MY129635A (en) | 2007-04-30 |
| AR030563A1 (es) | 2003-08-27 |
| BR0112674A (pt) | 2003-12-30 |
| LV13037B (en) | 2003-11-20 |
| KR20030016429A (ko) | 2003-02-26 |
| HRP20030116A2 (en) | 2005-02-28 |
| BG65132B1 (bg) | 2007-03-30 |
| CA2417254A1 (en) | 2002-02-07 |
| MXPA03000774A (es) | 2003-09-10 |
| CN1444584A (zh) | 2003-09-24 |
| CZ2003237A3 (cs) | 2003-06-18 |
| BG107468A (en) | 2004-01-30 |
| AU2001259704A1 (en) | 2002-02-13 |
| JP2004509857A (ja) | 2004-04-02 |
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