CA2788459C - Methods of synthesizing and isolating n-(bromoacetyl)-3,3-dinitroazetidine and a composition including the same - Google Patents
Methods of synthesizing and isolating n-(bromoacetyl)-3,3-dinitroazetidine and a composition including the same Download PDFInfo
- Publication number
- CA2788459C CA2788459C CA2788459A CA2788459A CA2788459C CA 2788459 C CA2788459 C CA 2788459C CA 2788459 A CA2788459 A CA 2788459A CA 2788459 A CA2788459 A CA 2788459A CA 2788459 C CA2788459 C CA 2788459C
- Authority
- CA
- Canada
- Prior art keywords
- abdnaz
- dnaz
- solvent
- approximately
- dichloromethane
- 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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Links
- JODKFOVZURLVTG-UHFFFAOYSA-N 2-bromo-1-(3,3-dinitroazetidin-1-yl)ethanone Chemical compound [O-][N+](=O)C1([N+]([O-])=O)CN(C(=O)CBr)C1 JODKFOVZURLVTG-UHFFFAOYSA-N 0.000 title claims abstract description 187
- 238000000034 method Methods 0.000 title claims abstract description 69
- 239000000203 mixture Substances 0.000 title claims abstract description 17
- 230000002194 synthesizing effect Effects 0.000 title abstract description 8
- 239000002904 solvent Substances 0.000 claims abstract description 106
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 62
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 claims abstract description 42
- LSTRKXWIZZZYAS-UHFFFAOYSA-N 2-bromoacetyl bromide Chemical compound BrCC(Br)=O LSTRKXWIZZZYAS-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000008346 aqueous phase Substances 0.000 claims abstract description 23
- 239000012074 organic phase Substances 0.000 claims abstract description 21
- 150000003839 salts Chemical class 0.000 claims abstract description 13
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 129
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 102
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 56
- 239000011541 reaction mixture Substances 0.000 claims description 33
- 239000000725 suspension Substances 0.000 claims description 11
- 239000002274 desiccant Substances 0.000 claims description 9
- 238000001704 evaporation Methods 0.000 claims description 7
- 238000010992 reflux Methods 0.000 claims description 7
- 238000001914 filtration Methods 0.000 claims description 5
- 239000013078 crystal Substances 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims description 3
- YNVDAIOEJHCEQA-UHFFFAOYSA-N 1-tert-butyl-3,3-dinitroazetidine Chemical compound CC(C)(C)N1CC([N+]([O-])=O)([N+]([O-])=O)C1 YNVDAIOEJHCEQA-UHFFFAOYSA-N 0.000 claims 2
- ZLYKMXLCTFBEGU-UHFFFAOYSA-N (1-tert-butyl-3-nitroazetidin-3-yl)methanol Chemical compound CC(C)(C)N1CC(CO)([N+]([O-])=O)C1 ZLYKMXLCTFBEGU-UHFFFAOYSA-N 0.000 claims 1
- 239000000243 solution Substances 0.000 description 73
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 61
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 51
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 24
- 230000008569 process Effects 0.000 description 22
- 238000006396 nitration reaction Methods 0.000 description 18
- 230000001590 oxidative effect Effects 0.000 description 17
- 239000007787 solid Substances 0.000 description 14
- 230000015572 biosynthetic process Effects 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- FMXOEQQPVONPBU-UHFFFAOYSA-N methylidene(dioxido)azanium Chemical compound [O-][N+]([O-])=C FMXOEQQPVONPBU-UHFFFAOYSA-N 0.000 description 12
- 235000010288 sodium nitrite Nutrition 0.000 description 12
- -1 Cyclic nitro compounds Chemical class 0.000 description 11
- 239000012535 impurity Substances 0.000 description 11
- 238000000605 extraction Methods 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- 238000003756 stirring Methods 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 238000002955 isolation Methods 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 239000003960 organic solvent Substances 0.000 description 7
- LCPVQAHEFVXVKT-UHFFFAOYSA-N 2-(2,4-difluorophenoxy)pyridin-3-amine Chemical compound NC1=CC=CN=C1OC1=CC=C(F)C=C1F LCPVQAHEFVXVKT-UHFFFAOYSA-N 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- CHQMHPLRPQMAMX-UHFFFAOYSA-L sodium persulfate Substances [Na+].[Na+].[O-]S(=O)(=O)OOS([O-])(=O)=O CHQMHPLRPQMAMX-UHFFFAOYSA-L 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- 239000006227 byproduct Substances 0.000 description 5
- 238000000354 decomposition reaction Methods 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 239000002360 explosive Substances 0.000 description 5
- 239000008194 pharmaceutical composition Substances 0.000 description 5
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- YAGKRVSRTSUGEY-UHFFFAOYSA-N ferricyanide Chemical compound [Fe+3].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] YAGKRVSRTSUGEY-UHFFFAOYSA-N 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- 239000011591 potassium Substances 0.000 description 4
- 238000003828 vacuum filtration Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- 0 CC(C)(C)N(C1)CC1(*)[N+]([O-])=O Chemical compound CC(C)(C)N(C1)CC1(*)[N+]([O-])=O 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 2
- 238000010936 aqueous wash Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000002051 biphasic effect Effects 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000005192 partition Methods 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000013557 residual solvent Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 239000006057 Non-nutritive feed additive Substances 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- KDPAWGWELVVRCH-UHFFFAOYSA-N bromoacetic acid Chemical compound OC(=O)CBr KDPAWGWELVVRCH-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 239000008241 heterogeneous mixture Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/04—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
-
- 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
- A61K31/397—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having four-membered rings, e.g. azetidine
-
- 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)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12/702,782 | 2010-02-09 | ||
| US12/702,782 US8471041B2 (en) | 2010-02-09 | 2010-02-09 | Methods of synthesizing and isolating N-(bromoacetyl)-3,3-dinitroazetidine and a composition including the same |
| PCT/US2011/021500 WO2011100090A1 (en) | 2010-02-09 | 2011-01-18 | Methods of synthesizing and isolating n-(bromoacetyl)-3,3-dinitroazetidine and a composition including the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2788459A1 CA2788459A1 (en) | 2011-08-18 |
| CA2788459C true CA2788459C (en) | 2016-01-05 |
Family
ID=43875262
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2788459A Active CA2788459C (en) | 2010-02-09 | 2011-01-18 | Methods of synthesizing and isolating n-(bromoacetyl)-3,3-dinitroazetidine and a composition including the same |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US8471041B2 (enExample) |
| EP (1) | EP2534131B1 (enExample) |
| JP (1) | JP5461712B2 (enExample) |
| KR (1) | KR101456438B1 (enExample) |
| CN (1) | CN102762535B (enExample) |
| AU (1) | AU2011216176B2 (enExample) |
| CA (1) | CA2788459C (enExample) |
| DK (1) | DK2534131T3 (enExample) |
| ES (1) | ES2460040T3 (enExample) |
| IL (1) | IL221141A (enExample) |
| MX (1) | MX2012008989A (enExample) |
| WO (1) | WO2011100090A1 (enExample) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7507842B2 (en) | 2005-08-12 | 2009-03-24 | Radiorx, Inc. | Cyclic nitro compounds, pharmaceutical compositions thereof and uses thereof |
| US20070135380A1 (en) | 2005-08-12 | 2007-06-14 | Radiorx, Inc. | O-nitro compounds, pharmaceutical compositions thereof and uses thereof |
| US8664247B2 (en) | 2011-08-26 | 2014-03-04 | Radiorx, Inc. | Acyclic organonitro compounds for use in treating cancer |
| EP2763667B1 (en) | 2011-10-07 | 2022-10-26 | EpicentRx, Inc. | Organonitro thioether compounds and medical uses thereof |
| WO2013052803A2 (en) | 2011-10-07 | 2013-04-11 | Radiorx, Inc. | Methods and compositions comprising a nitrite-reductase promoter for treatment of medical disorders and preservation of blood products |
| US10342778B1 (en) | 2015-10-20 | 2019-07-09 | Epicentrx, Inc. | Treatment of brain metastases using organonitro compound combination therapy |
| US9987270B1 (en) | 2015-10-29 | 2018-06-05 | Epicentrix, Inc. | Treatment of gliomas using organonitro compound combination therapy |
| AU2017207304B2 (en) | 2016-01-11 | 2022-05-26 | Epicentrx, Inc. | Compositions and methods for intravenous administration of 2-bromo-1-(3,3-dinitroazetidin-1-yl)ethanone |
| CA3040479A1 (en) | 2016-10-14 | 2018-04-19 | Epicentrx, Inc. | Sulfoxyalkyl organonitro and related compounds and pharmaceutical compositions for use in medicine |
| IL311727A (en) | 2017-07-07 | 2024-05-01 | Epicentrx Inc | Preparations for intravenous administration of medical substances |
| WO2019164593A2 (en) | 2018-01-08 | 2019-08-29 | Epicentrx, Inc. | Methods and compositions utilizing rrx-001 combination therapy for radioprotection |
| TW202313001A (zh) * | 2021-06-09 | 2023-04-01 | 美商埃皮辛特瑞科斯公司 | 結晶abdnaz組合物及其製造及使用方法 |
| WO2024145484A1 (en) | 2022-12-29 | 2024-07-04 | Epicentrx, Inc. | Rrx-001 for treating reproductive-related disorders |
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| US3845770A (en) | 1972-06-05 | 1974-11-05 | Alza Corp | Osmatic dispensing device for releasing beneficial agent |
| US3916899A (en) | 1973-04-25 | 1975-11-04 | Alza Corp | Osmotic dispensing device with maximum and minimum sizes for the passageway |
| US4935450A (en) | 1982-09-17 | 1990-06-19 | Therapeutical Systems Corporation | Cancer therapy system for effecting oncolysis of malignant neoplasms |
| JPS60116642A (ja) | 1983-11-29 | 1985-06-24 | Nippon Kayaku Co Ltd | ２−モノ−置換メチル−５，５−ジメチル−シクロ−２−ヘキセノン誘導体 |
| GB8504253D0 (en) | 1985-02-19 | 1985-03-20 | Ici Plc | Electrostatic spraying apparatus |
| GB8728418D0 (en) | 1987-12-04 | 1988-01-13 | Jenkins T C | Nitro-substituted aromatic/hetero-aromatic compounds for use in cancer treatment |
| DE3815221C2 (de) | 1988-05-04 | 1995-06-29 | Gradinger F Hermes Pharma | Verwendung einer Retinol- und/oder Retinsäureester enthaltenden pharmazeutischen Zubereitung zur Inhalation zur Einwirkung auf die Schleimhäute des Tracheo-Bronchialtraktes einschließlich der Lungenalveolen |
| US5693794A (en) | 1988-09-30 | 1997-12-02 | The United States Of America As Represented By The Secretary Of The Navy | Caged polynitramine compound |
| JP2659614B2 (ja) | 1990-11-13 | 1997-09-30 | 株式会社日立製作所 | 表示制御装置 |
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| EP1603933A2 (en) | 2003-03-13 | 2005-12-14 | Nitromed, Inc. | Nitrosated and nitrosylated compounds, compositions and methods of use |
| WO2004113281A1 (en) | 2003-06-25 | 2004-12-29 | Je Il Pharmaceutical Co., Ltd. | Tricyclic derivatives or pharmaceutically acceptable salts thereof, their preparations and pharmaceutical compositions containing them |
| GB0326047D0 (en) | 2003-11-07 | 2003-12-10 | Univ Sheffield | Substance |
| US7829708B2 (en) | 2004-09-08 | 2010-11-09 | Chelsea Therapeutics, Inc. | Metabolically inert antifolates for treating disorders of abnormal cellular proliferation and inflammation |
| US7507842B2 (en) * | 2005-08-12 | 2009-03-24 | Radiorx, Inc. | Cyclic nitro compounds, pharmaceutical compositions thereof and uses thereof |
| US20070135380A1 (en) | 2005-08-12 | 2007-06-14 | Radiorx, Inc. | O-nitro compounds, pharmaceutical compositions thereof and uses thereof |
| WO2007038459A2 (en) | 2005-09-27 | 2007-04-05 | Novartis Ag | Carboxyamine compounds and their use in the treatment of hdac dependent diseases |
| KR100967848B1 (ko) * | 2008-05-28 | 2010-07-05 | 국방과학연구소 | 분자화약이 도입된, 고에너지 결합제용1-글리시딜-3,3-디니트로아제티딘 및 그의 제조방법 |
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2011
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|---|---|
| US8471041B2 (en) | 2013-06-25 |
| KR101456438B1 (ko) | 2014-10-31 |
| AU2011216176A1 (en) | 2012-08-23 |
| WO2011100090A1 (en) | 2011-08-18 |
| DK2534131T3 (da) | 2014-04-07 |
| IL221141A0 (en) | 2012-09-24 |
| KR20130053385A (ko) | 2013-05-23 |
| US20110195947A1 (en) | 2011-08-11 |
| EP2534131B1 (en) | 2014-03-19 |
| CN102762535B (zh) | 2014-09-03 |
| AU2011216176B2 (en) | 2013-11-14 |
| EP2534131A1 (en) | 2012-12-19 |
| IL221141A (en) | 2016-08-31 |
| JP5461712B2 (ja) | 2014-04-02 |
| CN102762535A (zh) | 2012-10-31 |
| MX2012008989A (es) | 2012-08-23 |
| ES2460040T3 (es) | 2014-05-13 |
| JP2013518925A (ja) | 2013-05-23 |
| CA2788459A1 (en) | 2011-08-18 |
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