JP2007517886A - 新規な化学化合物 - Google Patents
新規な化学化合物 Download PDFInfo
- Publication number
- JP2007517886A JP2007517886A JP2006549383A JP2006549383A JP2007517886A JP 2007517886 A JP2007517886 A JP 2007517886A JP 2006549383 A JP2006549383 A JP 2006549383A JP 2006549383 A JP2006549383 A JP 2006549383A JP 2007517886 A JP2007517886 A JP 2007517886A
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- JP
- Japan
- Prior art keywords
- thiazole
- carboxylic acid
- methoxyphenyl
- formula
- pyridin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- WJKHJLXJJJATHN-UHFFFAOYSA-N trifluoromethanesulfonic anhydride Substances FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- 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
- C07D277/32—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 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
- C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- 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
- C07D417/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Virology (AREA)
- Diabetes (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Immunology (AREA)
- Hematology (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US53526704P | 2004-01-09 | 2004-01-09 | |
| US55197204P | 2004-03-10 | 2004-03-10 | |
| PCT/US2005/000303 WO2005070042A2 (en) | 2004-01-09 | 2005-01-06 | Novel chemical compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007517886A true JP2007517886A (ja) | 2007-07-05 |
| JP2007517886A5 JP2007517886A5 (https=) | 2007-10-11 |
Family
ID=34811305
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006549383A Pending JP2007517886A (ja) | 2004-01-09 | 2005-01-06 | 新規な化学化合物 |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US20090270456A1 (https=) |
| EP (1) | EP1718297A4 (https=) |
| JP (1) | JP2007517886A (https=) |
| WO (1) | WO2005070042A2 (https=) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008543735A (ja) * | 2005-05-12 | 2008-12-04 | セントロ デ インジエニエリア ジエネテイカ イ バイオテクノロジア | 抗腫瘍化合物及びその医薬組成物 |
| JP2013536193A (ja) * | 2010-08-11 | 2013-09-19 | ミレニアム ファーマシューティカルズ, インコーポレイテッド | ヘテロアリール類およびその使用 |
| JP2017518309A (ja) * | 2014-06-05 | 2017-07-06 | バイエル・クロップサイエンス・アクチェンゲゼルシャフト | 殺虫剤としての二環式化合物 |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PE20070083A1 (es) | 2005-06-08 | 2007-01-27 | Smithkline Beecham Corp | (5z)-5-(6-quinoxalinilmetilideno)-2-[(2,6-diclorofenil)amino]-1,3-tiazol-4(5h)-ona |
| CA2626789A1 (en) * | 2005-10-21 | 2007-04-26 | Exelixis, Inc. | Pyrimidinones as casein kinase ii (ck2) modulators |
| US8105581B2 (en) * | 2005-12-01 | 2012-01-31 | The Scripps Research Institute | Compositions and methods for inducing neuronal differentiation |
| US12319713B2 (en) | 2018-07-20 | 2025-06-03 | Arkansas State University—Jonesboro | 3,4-thiazolo-steroids and methods of making and using the same |
| WO2023192595A1 (en) * | 2022-03-31 | 2023-10-05 | Arkansas State University - Jonesboro | Thiazole derivatives and methods of using the same |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002057240A1 (en) * | 2000-12-22 | 2002-07-25 | Ortho Mc Neil Pharmaceutical, Inc. | Substituted triazole diamine derivatives as kinase inhibitors |
| WO2002081728A2 (en) * | 2001-04-06 | 2002-10-17 | Smithkline Beecham Corporation | Quinoline inhibitors of hyak1 and hyak3 kinases |
| EP1321463A1 (en) * | 2001-12-21 | 2003-06-25 | Shire Biochem Inc. | Thiazole derivatives and their use for the treatment or prevention of Flavivirus infections |
-
2005
- 2005-01-06 WO PCT/US2005/000303 patent/WO2005070042A2/en not_active Ceased
- 2005-01-06 EP EP05705093A patent/EP1718297A4/en not_active Withdrawn
- 2005-01-06 US US10/585,676 patent/US20090270456A1/en not_active Abandoned
- 2005-01-06 JP JP2006549383A patent/JP2007517886A/ja active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002057240A1 (en) * | 2000-12-22 | 2002-07-25 | Ortho Mc Neil Pharmaceutical, Inc. | Substituted triazole diamine derivatives as kinase inhibitors |
| WO2002081728A2 (en) * | 2001-04-06 | 2002-10-17 | Smithkline Beecham Corporation | Quinoline inhibitors of hyak1 and hyak3 kinases |
| EP1321463A1 (en) * | 2001-12-21 | 2003-06-25 | Shire Biochem Inc. | Thiazole derivatives and their use for the treatment or prevention of Flavivirus infections |
Non-Patent Citations (1)
| Title |
|---|
| JPN6010063084, DRIDI,K. et al, "Reaction of mercaptoacetate and halides containing activated methylenes with thiocarbamoylimidates:", Synthetic Communications, 1998, Vol.28, No.1, p.167−174 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008543735A (ja) * | 2005-05-12 | 2008-12-04 | セントロ デ インジエニエリア ジエネテイカ イ バイオテクノロジア | 抗腫瘍化合物及びその医薬組成物 |
| JP2013536193A (ja) * | 2010-08-11 | 2013-09-19 | ミレニアム ファーマシューティカルズ, インコーポレイテッド | ヘテロアリール類およびその使用 |
| JP2017518309A (ja) * | 2014-06-05 | 2017-07-06 | バイエル・クロップサイエンス・アクチェンゲゼルシャフト | 殺虫剤としての二環式化合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1718297A2 (en) | 2006-11-08 |
| US20090270456A1 (en) | 2009-10-29 |
| WO2005070042A2 (en) | 2005-08-04 |
| WO2005070042A3 (en) | 2005-09-29 |
| EP1718297A4 (en) | 2009-09-02 |
| WO2005070042A8 (en) | 2006-08-24 |
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