DE69533900T2 - Substituierte 6(4)-Benzyloxypyrimidine - Google Patents
Substituierte 6(4)-Benzyloxypyrimidine Download PDFInfo
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- DE69533900T2 DE69533900T2 DE69533900T DE69533900T DE69533900T2 DE 69533900 T2 DE69533900 T2 DE 69533900T2 DE 69533900 T DE69533900 T DE 69533900T DE 69533900 T DE69533900 T DE 69533900T DE 69533900 T2 DE69533900 T2 DE 69533900T2
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- Prior art keywords
- amino
- compound
- alkyl
- hydrogen
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- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
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- 229920000642 polymer Polymers 0.000 description 1
- 229920005606 polypropylene copolymer Polymers 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- RNVYQYLELCKWAN-UHFFFAOYSA-N solketal Chemical compound CC1(C)OCC(CO)O1 RNVYQYLELCKWAN-UHFFFAOYSA-N 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
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- 150000003432 sterols Chemical class 0.000 description 1
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- 238000007920 subcutaneous administration Methods 0.000 description 1
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- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
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- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/50—Three nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/26—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hetero atoms directly attached to ring carbon atoms
- C07D251/40—Nitrogen atoms
- C07D251/48—Two nitrogen atoms
- C07D251/52—Two nitrogen atoms with an oxygen or sulfur atom attached to the third ring carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/18—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/40—Heterocyclic compounds containing purine ring systems with halogen atoms or perhalogeno-alkyl radicals directly attached in position 2 or 6
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General 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)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Hydrogenated Pyridines (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US283953 | 1994-08-01 | ||
| US08/283,953 US5525606A (en) | 1994-08-01 | 1994-08-01 | Substituted 06-benzylguanines and 6(4)-benzyloxypyrimidines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69533900D1 DE69533900D1 (de) | 2005-02-03 |
| DE69533900T2 true DE69533900T2 (de) | 2005-12-29 |
Family
ID=23088285
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69533900T Expired - Fee Related DE69533900T2 (de) | 1994-08-01 | 1995-07-31 | Substituierte 6(4)-Benzyloxypyrimidine |
| DE69523462T Expired - Fee Related DE69523462T2 (de) | 1994-08-01 | 1995-07-31 | Substituierte o6-benzylguanine |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69523462T Expired - Fee Related DE69523462T2 (de) | 1994-08-01 | 1995-07-31 | Substituierte o6-benzylguanine |
Country Status (10)
| Country | Link |
|---|---|
| US (8) | US5525606A (https=) |
| EP (3) | EP1142893B1 (https=) |
| JP (2) | JP3981407B2 (https=) |
| AT (2) | ATE286054T1 (https=) |
| CA (2) | CA2632452A1 (https=) |
| DE (2) | DE69533900T2 (https=) |
| DK (2) | DK1142893T3 (https=) |
| ES (2) | ES2233513T3 (https=) |
| PT (2) | PT775142E (https=) |
| WO (1) | WO1996004281A1 (https=) |
Families Citing this family (55)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US6043228A (en) * | 1993-06-08 | 2000-03-28 | Cancer Research Campaign Technology Limited | O6 -substituted guanine derivatives, a process for their preparation and their use in treating tumor cells |
| US5929046A (en) * | 1994-06-08 | 1999-07-27 | Cancer Research Campaign Technology Limited | Pyrimidine and purine derivatives and their use in treating tumour cells |
| US5525606A (en) | 1994-08-01 | 1996-06-11 | The United States Of America As Represented By The Department Of Health And Human Services | Substituted 06-benzylguanines and 6(4)-benzyloxypyrimidines |
| US6794390B2 (en) * | 1996-08-02 | 2004-09-21 | Cv Therapeutics, Inc. | Purine inhibitors of cyclin dependent kinase 2 & ikappabalpha |
| DE19653646A1 (de) * | 1996-12-20 | 1998-06-25 | Hoechst Ag | Substituierte Purinderivate, Verfahren zu deren Herstellung, sie enthaltende Mittel und deren Verwendung |
| AU744986B2 (en) * | 1997-07-12 | 2002-03-07 | Cancer Research Technology Limited | Cyclin dependent kinase inhibiting purine derivatives |
| US6060458A (en) * | 1998-02-13 | 2000-05-09 | The United States Of America As Represented By The Department Of Health And Human Services | Oligodeoxyribonucleotides comprising O6 -benzylguanine and their use |
| GB9806739D0 (en) * | 1998-03-28 | 1998-05-27 | Univ Newcastle Ventures Ltd | Cyclin dependent kinase inhibitors |
| US6677345B1 (en) * | 1998-03-28 | 2004-01-13 | Cancer Research Campaign Technology Limited | Cyclin dependent kinase inhibitors |
| US6303607B1 (en) * | 1998-09-10 | 2001-10-16 | Cv Therapeutics, Inc. | Method for administering a sustained release ranolanolazine formulation |
| KR100368515B1 (ko) * | 1999-02-03 | 2003-01-24 | 주식회사 엘지생명과학 | 싸이클린 의존 키나아제 저해제 및 그의 제조 방법 |
| WO2008109417A1 (en) * | 2007-03-02 | 2008-09-12 | Case Western Reserve University | Mgmt inhibitor combinations for the treatment of neoplastic disorders |
| US6376514B1 (en) | 2000-10-17 | 2002-04-23 | The Procter & Gamble Co. | Substituted six-membered heterocyclic compounds useful for treating multidrug resistance and compositions and methods thereof |
| US6693099B2 (en) | 2000-10-17 | 2004-02-17 | The Procter & Gamble Company | Substituted piperazine compounds optionally containing a quinolyl moiety for treating multidrug resistance |
| AU2002216650A1 (en) | 2000-10-31 | 2002-05-15 | Lynn Bonham | Triazine derivatives as lpaat-b inhibitors and uses thereof |
| GB0101686D0 (en) * | 2001-01-23 | 2001-03-07 | Cancer Res Campaign Tech | Cyclin dependent kinase inhibitors |
| MXPA03007134A (es) * | 2001-02-08 | 2004-10-15 | Memory Pharm Corp | Trifluorometilpurinas como inhibidores de fosfodiesterasa 4. |
| JP4202250B2 (ja) | 2001-07-25 | 2008-12-24 | バイオマリン ファーマシューティカル インコーポレイテッド | 血液脳関門輸送を調節するための組成物および方法 |
| US20070129334A1 (en) * | 2001-10-30 | 2007-06-07 | Conforma Therapeutics Corporation | Orally Active Purine-Based Inhibitors of Heat Shock Protein 90 |
| US7241890B2 (en) * | 2001-10-30 | 2007-07-10 | Conforma Therapeutics Corporation | Purine analogs having HSP90-inhibiting activity |
| US7335654B2 (en) * | 2002-08-08 | 2008-02-26 | Memory Pharmaceuticals Corporation | Phosphodiesterase 4 inhibitors |
| ATE449099T1 (de) * | 2002-08-08 | 2009-12-15 | Memory Pharm Corp | Derivate des 2-trifluormethyl-6-aminopurins als phosphodiesterase 4 inhibitoren |
| GB0219746D0 (en) * | 2002-08-23 | 2002-10-02 | Inst Of Ex Botany Ascr | Azapurine derivatives |
| DE10307928A1 (de) * | 2003-02-25 | 2004-09-16 | Faustus Forschungs Cie. Translational Cancer Research Gmbh | Verwendung von 1-(2-Chlorethyl)-1-nitroso-3-(2-hydroxyethyl)-urea zur Behandlung von Pankreaskarzinomen, Weichteilsarkomen, Hodentumoren, Lymphomen, Thymomen, Wilms Tumoren, Nierenkarzinomen, Melanomen, Lungentumoren, intracerebralen Metastasen, Tumoren im Kopf- und Halsbereich, und Mamma-Karzinomen |
| KR20060070572A (ko) * | 2003-09-18 | 2006-06-23 | 콘포마 세러퓨틱스 코포레이션 | Ｈｓｐ90-저해제로서의 신규 헤테로시클릭 화합물 |
| AU2004313931A1 (en) * | 2004-01-06 | 2005-07-28 | Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services | 2-amino-O4-substituted pteridines and their use as inactivators of O6-alkylguanine-DNA alkyltransferase |
| WO2005107472A1 (en) * | 2004-05-12 | 2005-11-17 | Bayer Cropscience Gmbh | Plant growth regulation |
| WO2006029065A1 (en) * | 2004-09-08 | 2006-03-16 | Goverment Of The United States Of America Represented By The Secretary, Department Of Health And Human Services | Beta-gluguronidase cleavable prodrugs of o6-alkylguanine-dna alkyltransferase inactivators |
| US7825096B2 (en) * | 2004-09-08 | 2010-11-02 | The United States Of America As Represented By The Department Of Health And Human Services | O6-alkylguanine-DNA alkyltransferase inactivators and beta-glucuronidase cleavable prodrugs |
| CN100386115C (zh) * | 2004-10-14 | 2008-05-07 | 孔庆忠 | 一种抗癌药物组合物 |
| GB0502573D0 (en) * | 2005-02-08 | 2005-03-16 | Topotarget As | Therapeutic compounds |
| CA2602257A1 (en) | 2005-03-30 | 2006-10-05 | Conforma Therapeutics Corporation | Alkynyl pyrrolopyrimidines and related analogs as hsp90-inhibitors |
| WO2006114409A1 (en) * | 2005-04-27 | 2006-11-02 | Covalys Biosciences Ag | Pyrimidines reacting with o6-alkylguanine-dna alkyltransferase |
| EP2671507A3 (en) | 2005-04-28 | 2014-02-19 | Proteus Digital Health, Inc. | Pharma-informatics system |
| ES2577514T3 (es) * | 2005-08-22 | 2016-07-15 | The Regents Of The University Of California | Antagonistas de TLR |
| US20070105874A1 (en) * | 2005-09-23 | 2007-05-10 | Conforma Therapeutics Corporation | Anti-Tumor Methods Using Multi Drug Resistance Independent Synthetic HSP90 Inhibitors |
| EP2029597A4 (en) * | 2006-05-31 | 2011-11-23 | Univ California | purine analogs |
| MX2009002893A (es) | 2006-09-18 | 2009-07-10 | Raptor Pharmaceutical Inc | Tratamiento de trastornos hepaticos mediante la administracion de conjugados de la proteina asociada al receptor (rap). |
| ES2552471T3 (es) | 2007-02-07 | 2015-11-30 | The Regents Of The University Of California | Conjugados de agonistas de TLR sintéticos y usos de los mismos |
| US8188055B2 (en) * | 2007-05-02 | 2012-05-29 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Inactivators of O6-alkylguanine-DNA alkyltransferase |
| EP1990661B1 (en) | 2007-05-07 | 2018-08-15 | CSEM Centre Suisse d'Electronique et de Microtechnique SA - Recherche et Développement | Isotropic zero-order diffractive filter |
| EA201001264A1 (ru) * | 2008-02-07 | 2011-04-29 | Дзе Регентс Оф Дзе Юниверсити Оф Калифорния | Способ лечения заболеваний мочевого пузыря с помощью активатора tlr7 |
| WO2010088924A1 (en) | 2009-02-06 | 2010-08-12 | Telormedix Sa | Pharmaceutical compositions comprising imidazoquinolin(amines) and derivatives thereof suitable for local administration |
| KR20110117705A (ko) * | 2009-02-11 | 2011-10-27 | 더 리전트 오브 더 유니버시티 오브 캘리포니아 | 톨-유사 수용체 조정제 및 질병의 치료 |
| CA2752373C (en) | 2009-02-20 | 2017-10-10 | To-Bbb Holding B.V. | Glutathione-based drug delivery system |
| IL255113B (en) | 2009-05-06 | 2022-09-01 | Laboratory Skin Care Inc | Dermal delivery compositions comprising active agent-calcium phosphate particle complexes and methods of using the same |
| WO2011028507A2 (en) * | 2009-08-24 | 2011-03-10 | Duke University | Compositions, methods, and kits for determining an alkyl transferase |
| CN101850504B (zh) * | 2010-05-06 | 2011-11-16 | 陕西理工学院 | 一种用两个步进电机控制主轴运动的振动制孔装置 |
| US20120077778A1 (en) | 2010-09-29 | 2012-03-29 | Andrea Bourdelais | Ladder-Frame Polyether Conjugates |
| GB201106814D0 (en) * | 2011-04-21 | 2011-06-01 | Astex Therapeutics Ltd | New compounds |
| KR20180084153A (ko) * | 2011-06-10 | 2018-07-24 | 메르크 파텐트 게엠베하 | Btk 억제 활성을 갖는 피리미딘 및 피리딘 화합물의 조성물 및 제조방법 |
| US20130236504A1 (en) * | 2012-03-06 | 2013-09-12 | Medical University Of South Carolina | Delivery System for Enhancing Drug Efficacy |
| US9775835B2 (en) | 2012-08-06 | 2017-10-03 | Sirga Advanced Biopharma, Inc. | Small molecule inhibitors of viral protein interactions with human t-RNA |
| ES2688194T3 (es) * | 2014-09-11 | 2018-10-31 | Bristol-Myers Squibb Company | Inhibidores de mieloperoxidasa de triazolopirimidina y triazolopiridina de tioéter |
| US11697851B2 (en) | 2016-05-24 | 2023-07-11 | The Regents Of The University Of California | Early ovarian cancer detection diagnostic test based on mRNA isoforms |
Family Cites Families (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4199574A (en) * | 1974-09-02 | 1980-04-22 | Burroughs Wellcome Co. | Methods and compositions for treating viral infections and guanine acyclic nucleosides |
| US4235871A (en) | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
| IL64501A (en) * | 1980-12-22 | 1985-07-31 | Astra Laekemedel Ab | 9-substituted 4-hydroxybutyl guanine derivatives,their preparation and antiviral use |
| US5260291A (en) | 1981-08-24 | 1993-11-09 | Cancer Research Campaign Technology Limited | Tetrazine derivatives |
| US5731304A (en) * | 1982-08-23 | 1998-03-24 | Cancer Research Campaign Technology | Potentiation of temozolomide in human tumour cells |
| US4501728A (en) | 1983-01-06 | 1985-02-26 | Technology Unlimited, Inc. | Masking of liposomes from RES recognition |
| DE3485225D1 (de) * | 1983-08-18 | 1991-12-05 | Beecham Group Plc | Antivirale guanin-derivate. |
| US5019369A (en) | 1984-10-22 | 1991-05-28 | Vestar, Inc. | Method of targeting tumors in humans |
| US4801710A (en) * | 1984-10-26 | 1989-01-31 | Merck & Co., Inc. | Regioselective synthesis of 9-substituted purine acyclonucleoside derivatives |
| EP0184473A1 (en) * | 1984-10-26 | 1986-06-11 | Merck & Co. Inc. | Regioselective synthesis of 9-substituted purine acyclonucleoside derivatives |
| US4751221A (en) * | 1985-10-18 | 1988-06-14 | Sloan-Kettering Institute For Cancer Research | 2-fluoro-arabinofuranosyl purine nucleosides |
| US4837028A (en) | 1986-12-24 | 1989-06-06 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| US4965270A (en) * | 1987-05-30 | 1990-10-23 | Beecham Group P.L.C. | Purine derivatives |
| US5723609A (en) * | 1988-03-30 | 1998-03-03 | E. R. Squibb & Sons, Inc. | Bis (hydroxymethyl) cyclobutyl purines |
| US5091430A (en) * | 1990-03-13 | 1992-02-25 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | O6 -substituted guanine compounds and methods for depleting O6 -alkylguanine-DNA alkyltransferase levels |
| US5691307A (en) * | 1990-03-13 | 1997-11-25 | The United States Of America As Represented By The Department Of Health And Human Services | O6 -substituted guanine compositions and methods for depleting O6 |
| US5352669A (en) * | 1990-03-13 | 1994-10-04 | The Of The United States Of America As Represented By The Department Of Health And Human Services | O6 -benzylated guanine, guanosine and 2'-deoxyguanosine compounds possessing O6 -alkylguanine-DNA alkyltransferase depleting activity |
| US5364904A (en) * | 1990-06-29 | 1994-11-15 | Unilever Patent Holdings B.V. | Emulsion polymerization |
| FR2676058B1 (fr) | 1991-04-30 | 1994-02-25 | Hoechst Lab | Prodrogues glycosylees, leur procede de preparation et leur utilisation dans le traitement des cancers. |
| NZ244306A (en) * | 1991-09-30 | 1995-07-26 | Boehringer Ingelheim Int | Composition for introducing nucleic acid complexes into eucaryotic cells, complex containing nucleic acid and endosomolytic agent, peptide with endosomolytic domain and nucleic acid binding domain and preparation |
| DE4236237A1 (de) | 1992-10-27 | 1994-04-28 | Behringwerke Ag | Prodrugs, ihre Herstellung und Verwendung als Arzneimittel |
| DE4311651A1 (de) * | 1993-04-08 | 1994-10-13 | Boehringer Ingelheim Int | Virus für den Transport von Fremd-DNA in höhere eukaryotische Zellen |
| DK0702683T3 (da) | 1993-06-08 | 2004-02-02 | Cancer Rec Tech Ltd | 06-substituerede guaninderivater, fremgangsmåde til fremstilling deraf og anvendelse deraf i behandling af tumorceller |
| US6043228A (en) | 1993-06-08 | 2000-03-28 | Cancer Research Campaign Technology Limited | O6 -substituted guanine derivatives, a process for their preparation and their use in treating tumor cells |
| EP0647450A1 (en) | 1993-09-09 | 1995-04-12 | BEHRINGWERKE Aktiengesellschaft | Improved prodrugs for enzyme mediated activation |
| EP0648503B1 (en) | 1993-09-22 | 2000-07-26 | Hoechst Aktiengesellschaft | Pro-prodrugs, their production and use |
| US5929046A (en) | 1994-06-08 | 1999-07-27 | Cancer Research Campaign Technology Limited | Pyrimidine and purine derivatives and their use in treating tumour cells |
| US5525606A (en) | 1994-08-01 | 1996-06-11 | The United States Of America As Represented By The Department Of Health And Human Services | Substituted 06-benzylguanines and 6(4)-benzyloxypyrimidines |
| DK0795334T3 (da) | 1996-03-12 | 2006-06-06 | Sanofi Aventis Deutschland | Nye prodrugs til behandling af tumorer og betændelsessygdomme |
| US5965126A (en) | 1996-03-25 | 1999-10-12 | The Penn State Research Foundation | use of mutant alkyltransferases for gene therapy to protect from toxicity of therapeutic alkylating agents |
| AU1406499A (en) | 1997-11-13 | 1999-06-07 | Case Western Reserve University | Delta-o6-methylguanine-dna methyltransferase gene transfer for o6-benzylguanine and (n,n'-bis(2-chloroethyl)-n-nitrosourea) resistance |
-
1994
- 1994-08-01 US US08/283,953 patent/US5525606A/en not_active Expired - Lifetime
-
1995
- 1995-07-31 JP JP50669496A patent/JP3981407B2/ja not_active Expired - Lifetime
- 1995-07-31 AT AT01108585T patent/ATE286054T1/de not_active IP Right Cessation
- 1995-07-31 DK DK01108585T patent/DK1142893T3/da active
- 1995-07-31 DE DE69533900T patent/DE69533900T2/de not_active Expired - Fee Related
- 1995-07-31 CA CA002632452A patent/CA2632452A1/en not_active Abandoned
- 1995-07-31 US US08/849,223 patent/US5958932A/en not_active Expired - Fee Related
- 1995-07-31 EP EP01108585A patent/EP1142893B1/en not_active Expired - Lifetime
- 1995-07-31 EP EP95928237A patent/EP0775142B1/en not_active Expired - Lifetime
- 1995-07-31 EP EP04030121A patent/EP1518854A1/en not_active Withdrawn
- 1995-07-31 AT AT95928237T patent/ATE207490T1/de not_active IP Right Cessation
- 1995-07-31 WO PCT/US1995/009702 patent/WO1996004281A1/en not_active Ceased
- 1995-07-31 ES ES01108585T patent/ES2233513T3/es not_active Expired - Lifetime
- 1995-07-31 PT PT95928237T patent/PT775142E/pt unknown
- 1995-07-31 DE DE69523462T patent/DE69523462T2/de not_active Expired - Fee Related
- 1995-07-31 PT PT01108585T patent/PT1142893E/pt unknown
- 1995-07-31 DK DK95928237T patent/DK0775142T3/da active
- 1995-07-31 ES ES95928237T patent/ES2167451T3/es not_active Expired - Lifetime
- 1995-07-31 CA CA002195856A patent/CA2195856C/en not_active Expired - Fee Related
-
1996
- 1996-06-11 US US08/661,923 patent/US5753668A/en not_active Expired - Lifetime
-
1997
- 1997-09-11 US US08/927,846 patent/US5916894A/en not_active Expired - Fee Related
-
1999
- 1999-05-25 US US09/318,238 patent/US6172070B1/en not_active Expired - Fee Related
- 1999-06-15 US US09/333,047 patent/US6333331B1/en not_active Expired - Fee Related
-
2000
- 2000-06-09 US US09/590,187 patent/US6303604B1/en not_active Expired - Fee Related
-
2001
- 2001-08-14 US US09/928,410 patent/US6436945B2/en not_active Expired - Fee Related
-
2006
- 2006-10-04 JP JP2006273447A patent/JP2007077157A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CA2632452A1 (en) | 1996-02-15 |
| ES2167451T3 (es) | 2002-05-16 |
| AU3207995A (en) | 1996-03-04 |
| EP0775142A1 (en) | 1997-05-28 |
| US6436945B2 (en) | 2002-08-20 |
| ES2233513T3 (es) | 2005-06-16 |
| PT775142E (pt) | 2002-04-29 |
| DK1142893T3 (da) | 2005-03-29 |
| US5753668A (en) | 1998-05-19 |
| EP0775142B1 (en) | 2001-10-24 |
| US6333331B1 (en) | 2001-12-25 |
| AU702711B2 (en) | 1999-03-04 |
| EP1142893A1 (en) | 2001-10-10 |
| US5525606A (en) | 1996-06-11 |
| DE69523462T2 (de) | 2002-07-11 |
| DK0775142T3 (da) | 2002-02-18 |
| EP1518854A1 (en) | 2005-03-30 |
| US6172070B1 (en) | 2001-01-09 |
| JP3981407B2 (ja) | 2007-09-26 |
| DE69533900D1 (de) | 2005-02-03 |
| JP2007077157A (ja) | 2007-03-29 |
| US20020013299A1 (en) | 2002-01-31 |
| EP1142893B1 (en) | 2004-12-29 |
| ATE207490T1 (de) | 2001-11-15 |
| DE69523462D1 (de) | 2001-11-29 |
| US5958932A (en) | 1999-09-28 |
| WO1996004281A1 (en) | 1996-02-15 |
| JPH10508288A (ja) | 1998-08-18 |
| PT1142893E (pt) | 2005-04-29 |
| CA2195856C (en) | 2008-09-30 |
| CA2195856A1 (en) | 1996-02-15 |
| US5916894A (en) | 1999-06-29 |
| US6303604B1 (en) | 2001-10-16 |
| ATE286054T1 (de) | 2005-01-15 |
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