CA2852914C - Meldrum's acid, barbituric acid and pyrazolone derivatives substituted with hydroxylamine as hno donors - Google Patents
Meldrum's acid, barbituric acid and pyrazolone derivatives substituted with hydroxylamine as hno donors Download PDFInfo
- Publication number
- CA2852914C CA2852914C CA2852914A CA2852914A CA2852914C CA 2852914 C CA2852914 C CA 2852914C CA 2852914 A CA2852914 A CA 2852914A CA 2852914 A CA2852914 A CA 2852914A CA 2852914 C CA2852914 C CA 2852914C
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- CA
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- Prior art keywords
- compound
- alkyl
- aryl
- substituted
- unsubstituted
- Prior art date
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- HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical group O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 title description 9
- GXHFUVWIGNLZSC-UHFFFAOYSA-N meldrum's acid Chemical compound CC1(C)OC(=O)CC(=O)O1 GXHFUVWIGNLZSC-UHFFFAOYSA-N 0.000 title description 8
- JEXVQSWXXUJEMA-UHFFFAOYSA-N pyrazol-3-one Chemical group O=C1C=CN=N1 JEXVQSWXXUJEMA-UHFFFAOYSA-N 0.000 title description 7
- 229940083761 high-ceiling diuretics pyrazolone derivative Drugs 0.000 title description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N hydroxylamine group Chemical group NO AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 251
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 94
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 57
- ODUCDPQEXGNKDN-UHFFFAOYSA-N nitroxyl Chemical compound O=N ODUCDPQEXGNKDN-UHFFFAOYSA-N 0.000 claims abstract description 55
- 201000010099 disease Diseases 0.000 claims abstract description 52
- 208000002815 pulmonary hypertension Diseases 0.000 claims abstract description 37
- 208000028867 ischemia Diseases 0.000 claims abstract description 30
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 18
- 206010063837 Reperfusion injury Diseases 0.000 claims abstract description 13
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 104
- 125000001424 substituent group Chemical group 0.000 claims description 82
- 125000003118 aryl group Chemical group 0.000 claims description 65
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 65
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 59
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 43
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 37
- 125000004366 heterocycloalkenyl group Chemical group 0.000 claims description 36
- 125000001072 heteroaryl group Chemical group 0.000 claims description 34
- 125000000304 alkynyl group Chemical group 0.000 claims description 28
- 125000003342 alkenyl group Chemical group 0.000 claims description 27
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 22
- 125000003545 alkoxy group Chemical group 0.000 claims description 21
- 125000000172 C5-C10 aryl group Chemical group 0.000 claims description 19
- 238000001727 in vivo Methods 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 15
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 12
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 11
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 5
- 229910006074 SO2NH2 Inorganic materials 0.000 claims description 3
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 3
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 238000000034 method Methods 0.000 abstract description 55
- -1 N-substituted hydroxylamine Chemical class 0.000 abstract description 39
- 238000011161 development Methods 0.000 abstract description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 83
- 239000000243 solution Substances 0.000 description 41
- 238000006243 chemical reaction Methods 0.000 description 40
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- 101150041968 CDC13 gene Proteins 0.000 description 36
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 36
- 238000005160 1H NMR spectroscopy Methods 0.000 description 34
- 206010019280 Heart failures Diseases 0.000 description 31
- 241001465754 Metazoa Species 0.000 description 31
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
- 125000001246 bromo group Chemical group Br* 0.000 description 29
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 238000001802 infusion Methods 0.000 description 21
- GQPLMRYTRLFLPF-UHFFFAOYSA-N Nitrous Oxide Chemical compound [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 description 20
- 241000700159 Rattus Species 0.000 description 20
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
- 125000001309 chloro group Chemical group Cl* 0.000 description 20
- 239000003814 drug Substances 0.000 description 20
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 19
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 19
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
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- QPNKYNYIKKVVQB-UHFFFAOYSA-N crotaleschenine Natural products O1C(=O)C(C)C(C)C(C)(O)C(=O)OCC2=CCN3C2C1CC3 QPNKYNYIKKVVQB-UHFFFAOYSA-N 0.000 description 15
- QVCMHGGNRFRMAD-XFGHUUIASA-N monocrotaline Chemical compound C1OC(=O)[C@](C)(O)[C@@](O)(C)[C@@H](C)C(=O)O[C@@H]2CCN3[C@@H]2C1=CC3 QVCMHGGNRFRMAD-XFGHUUIASA-N 0.000 description 15
- QVCMHGGNRFRMAD-UHFFFAOYSA-N monocrotaline Natural products C1OC(=O)C(C)(O)C(O)(C)C(C)C(=O)OC2CCN3C2C1=CC3 QVCMHGGNRFRMAD-UHFFFAOYSA-N 0.000 description 15
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- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- 238000004458 analytical method Methods 0.000 description 12
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 12
- 239000006227 byproduct Substances 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 210000000056 organ Anatomy 0.000 description 12
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 12
- 230000010410 reperfusion Effects 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- JMMCYSCEKRWYEJ-UHFFFAOYSA-M chembl1627016 Chemical compound [Na+].[Na+].[O-]N=[N+]([O-])[O-] JMMCYSCEKRWYEJ-UHFFFAOYSA-M 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
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- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 10
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
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- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 7
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
- C07D319/06—1,3-Dioxanes; Hydrogenated 1,3-dioxanes not condensed with other rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/06—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D231/08—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with oxygen or sulfur atoms directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole 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
- C07D231/18—One oxygen or sulfur atom
- C07D231/20—One oxygen atom attached in position 3 or 5
- C07D231/22—One oxygen atom attached in position 3 or 5 with aryl radicals attached to ring nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole 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
- C07D231/44—Oxygen and nitrogen or sulfur and nitrogen atoms
- C07D231/46—Oxygen atom in position 3 or 5 and nitrogen atom in position 4
-
- 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
- C07D239/60—Three or more oxygen or sulfur atoms
- C07D239/62—Barbituric acids
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
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|---|---|---|---|
| US201161548036P | 2011-10-17 | 2011-10-17 | |
| US61/548,036 | 2011-10-17 | ||
| PCT/US2012/060425 WO2013059194A1 (en) | 2011-10-17 | 2012-10-16 | Meldrum 's acid, barbituric acid and pyrazolone derivatives substituted with hydroxylamine as hno donors |
Publications (2)
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| CA2852914A1 CA2852914A1 (en) | 2013-04-25 |
| CA2852914C true CA2852914C (en) | 2019-11-26 |
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| CA2852914A Active CA2852914C (en) | 2011-10-17 | 2012-10-16 | Meldrum's acid, barbituric acid and pyrazolone derivatives substituted with hydroxylamine as hno donors |
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| US (3) | US9181213B2 (enExample) |
| EP (1) | EP2776402B1 (enExample) |
| JP (1) | JP6177246B2 (enExample) |
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| CN (2) | CN104053647B (enExample) |
| AU (2) | AU2013201929B2 (enExample) |
| BR (1) | BR112014009282B1 (enExample) |
| CA (1) | CA2852914C (enExample) |
| HK (1) | HK1200168A1 (enExample) |
| IL (1) | IL232101A (enExample) |
| MX (1) | MX363306B (enExample) |
| SG (1) | SG11201401587QA (enExample) |
| WO (1) | WO2013059194A1 (enExample) |
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| CN104053647B (zh) | 2011-10-17 | 2018-06-01 | 约翰斯霍普金斯大学 | 作为hno供体的经羟胺取代的米氏酸、巴比妥酸和吡唑啉酮衍生物 |
| PL2945620T3 (pl) | 2013-01-18 | 2018-03-30 | Cardioxyl Pharmaceuticals, Inc. | Donory nitroksylu o korzystniejszym indeksie terapeutycznym |
| EP3126329B1 (en) | 2014-01-17 | 2019-05-29 | Cardioxyl Pharmaceuticals Inc. | N-hydroxymethanesulfonamide nitroxyl donors |
| EP3148972B1 (en) * | 2014-05-27 | 2019-08-21 | Cardioxyl Pharmaceuticals, Inc. | Pyrazolone derivatives as nitroxyl donors |
| EP3148983A1 (en) | 2014-05-27 | 2017-04-05 | The Johns Hopkins University | N-hydroxylamino-barbituric acid derivatives as nitroxyl donors |
| US9464061B2 (en) * | 2014-05-27 | 2016-10-11 | The Johns Hopkins University | N-hydroxylamino-barbituric acid derivatives |
| WO2016210392A1 (en) * | 2015-06-26 | 2016-12-29 | The Johns Hopkins University | N-substituted hydroxamic acids with carbon-based leaving groups as efficient hno donors and uses thereof |
| EP3365325A1 (en) | 2015-10-19 | 2018-08-29 | Cardioxyl Pharmaceuticals Inc. | N-hydroxylsulfonamide derivatives as nitroxyl donors |
| EP3365328A1 (en) * | 2015-10-19 | 2018-08-29 | Cardioxyl Pharmaceuticals, Inc. | Pyrazolone derivatives as nitroxyl donors |
| KR20190070912A (ko) * | 2016-07-28 | 2019-06-21 | 더 존스 홉킨스 유니버시티 | O-치환된 히드록삼산 |
| CA3049003A1 (en) | 2017-01-03 | 2018-07-12 | Cardioxyl Pharmaceuticals, Inc. | Method of administering nitroxyl donating compounds |
| IL277071B2 (en) | 2018-03-08 | 2024-07-01 | Incyte Corp | AMINOPYRAZINE DIOL COMPOUNDS AS PI3K-y INHIBITORS |
| US11046658B2 (en) | 2018-07-02 | 2021-06-29 | Incyte Corporation | Aminopyrazine derivatives as PI3K-γ inhibitors |
| US11912647B2 (en) | 2020-05-22 | 2024-02-27 | University Of Georgia Research Foundation, Inc. | Diversity-oriented synthesis of N,N,O-trisubstituted hydroxylamines from alcohols and amines by N—O bond formation |
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| US3751255A (en) | 1972-03-24 | 1973-08-07 | Eastman Kodak Co | Photosensitive and thermosensitive element, composition and process |
| JPS567710A (en) | 1979-06-28 | 1981-01-27 | Sansho Seiyaku Kk | Whitening cosmetic |
| US4539321A (en) | 1981-10-26 | 1985-09-03 | William H. Rorer, Inc. | 5-Diaza-aryl-3-substituted pyridone compounds |
| DE3583799D1 (de) | 1985-01-11 | 1991-09-19 | Abbott Lab Ltd | Feste zubereitung mit langsamer freisetzung. |
| US4663351A (en) | 1985-08-23 | 1987-05-05 | Berlex Laboratories, Inc. | Dobutamine tri-isobutyric acid ester and the use thereof as a cardiotonic agent |
| US4798824A (en) | 1985-10-03 | 1989-01-17 | Wisconsin Alumni Research Foundation | Perfusate for the preservation of organs |
| JP2773959B2 (ja) | 1990-07-10 | 1998-07-09 | 信越化学工業株式会社 | 大腸内放出性固形製剤 |
| WO1999021844A1 (en) | 1997-10-24 | 1999-05-06 | Shionogi & Co., Ltd. | Antirheumatic |
| UA73092C2 (uk) | 1998-07-17 | 2005-06-15 | Брістол-Майерс Сквібб Компані | Таблетка з ентеросолюбільним покриттям і спосіб її приготування |
| KR100501022B1 (ko) | 1998-07-28 | 2005-07-18 | 다나베 세이야꾸 가부시키가이샤 | 장내 적소 방출형 제제 |
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| GB0114223D0 (en) | 2001-06-12 | 2001-08-01 | Ici Plc | Catalytic oxidation process |
| US20040038947A1 (en) | 2002-06-14 | 2004-02-26 | The Gov. Of The U.S. Of America As Represented By The Sec. Of The Dept. Of Health & Human Services | Method of treating ischemia/reperfusion injury with nitroxyl donors |
| US6936639B2 (en) | 2002-08-21 | 2005-08-30 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Nitroxyl progenitors in the treatment of heart failure |
| JP2007514759A (ja) | 2003-12-19 | 2007-06-07 | タケダ サン ディエゴ インコーポレイテッド | キナーゼ阻害剤 |
| EP1718621A4 (en) | 2004-01-30 | 2009-08-19 | Univ Johns Hopkins | NITROXYL PREPARATION COMPOUNDS APPLICATION METHOD |
| US8168771B2 (en) | 2005-01-31 | 2012-05-01 | The Johns Hopkins University | Use of consensus sequence as vaccine antigen to enhance recognition of virulent viral variants |
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| NZ584036A (en) | 2007-09-26 | 2012-06-29 | Univ Johns Hopkins | N-hydroxylsulfonamide derivatives as new physiologically useful nitroxyl donors |
| US8318705B2 (en) * | 2008-05-07 | 2012-11-27 | Cardioxyl Pharmaceuticals, Inc. | Nitroso compounds as nitroxyl donors and methods of use thereof |
| WO2011063339A1 (en) | 2009-11-23 | 2011-05-26 | Cardioxyl Pharmaceuticals, Inc. | Nitroxyl donors for the treatment of pulmonary hypertension |
| CN102753519B (zh) * | 2009-12-07 | 2015-08-05 | 约翰斯霍普金斯大学 | 二酰基化的羟基胺衍生物 |
| CA2782110A1 (en) | 2009-12-07 | 2011-06-16 | Johns Hopkins University | N-acyloxysulfonamide and n-hydroxy-n-acylsulfonamide derivatives |
| CN104053647B (zh) | 2011-10-17 | 2018-06-01 | 约翰斯霍普金斯大学 | 作为hno供体的经羟胺取代的米氏酸、巴比妥酸和吡唑啉酮衍生物 |
| PL2945620T3 (pl) | 2013-01-18 | 2018-03-30 | Cardioxyl Pharmaceuticals, Inc. | Donory nitroksylu o korzystniejszym indeksie terapeutycznym |
| US9464061B2 (en) | 2014-05-27 | 2016-10-11 | The Johns Hopkins University | N-hydroxylamino-barbituric acid derivatives |
| EP3148972B1 (en) | 2014-05-27 | 2019-08-21 | Cardioxyl Pharmaceuticals, Inc. | Pyrazolone derivatives as nitroxyl donors |
| EP3148983A1 (en) | 2014-05-27 | 2017-04-05 | The Johns Hopkins University | N-hydroxylamino-barbituric acid derivatives as nitroxyl donors |
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2012
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- 2012-10-16 KR KR1020147013269A patent/KR102061537B1/ko not_active Expired - Fee Related
- 2012-10-16 MX MX2014004596A patent/MX363306B/es unknown
- 2012-10-16 CA CA2852914A patent/CA2852914C/en active Active
- 2012-10-16 EP EP12781538.9A patent/EP2776402B1/en active Active
- 2012-10-16 AU AU2013201929A patent/AU2013201929B2/en not_active Ceased
- 2012-10-16 HK HK15100597.0A patent/HK1200168A1/xx unknown
- 2012-10-16 JP JP2014537151A patent/JP6177246B2/ja not_active Expired - Fee Related
- 2012-10-16 SG SG11201401587QA patent/SG11201401587QA/en unknown
- 2012-10-16 CN CN201810435608.5A patent/CN108409662B/zh not_active Expired - Fee Related
- 2012-10-16 BR BR112014009282-6A patent/BR112014009282B1/pt not_active IP Right Cessation
- 2012-10-16 WO PCT/US2012/060425 patent/WO2013059194A1/en not_active Ceased
- 2012-10-16 US US14/352,399 patent/US9181213B2/en active Active
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2014
- 2014-04-13 IL IL232101A patent/IL232101A/en active IP Right Grant
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2015
- 2015-10-21 AU AU2015246114A patent/AU2015246114A1/en not_active Abandoned
- 2015-10-29 US US14/927,039 patent/US9499511B2/en active Active
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- 2016-10-11 US US15/290,872 patent/US9862699B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| KR102061537B1 (ko) | 2020-01-03 |
| US20170050947A1 (en) | 2017-02-23 |
| MX2014004596A (es) | 2014-09-04 |
| CN104053647B (zh) | 2018-06-01 |
| AU2015246114A1 (en) | 2015-11-12 |
| CN108409662A (zh) | 2018-08-17 |
| SG11201401587QA (en) | 2014-07-30 |
| AU2013201929A1 (en) | 2013-05-02 |
| BR112014009282A8 (pt) | 2020-04-22 |
| MX363306B (es) | 2019-03-20 |
| CN104053647A (zh) | 2014-09-17 |
| EP2776402A1 (en) | 2014-09-17 |
| BR112014009282A2 (pt) | 2017-06-13 |
| AU2013201929B2 (en) | 2015-07-23 |
| US20140275134A1 (en) | 2014-09-18 |
| CN108409662B (zh) | 2021-10-26 |
| US20160115148A1 (en) | 2016-04-28 |
| US9862699B2 (en) | 2018-01-09 |
| JP2015501308A (ja) | 2015-01-15 |
| US9181213B2 (en) | 2015-11-10 |
| JP6177246B2 (ja) | 2017-08-09 |
| EP2776402B1 (en) | 2017-07-26 |
| CA2852914A1 (en) | 2013-04-25 |
| IL232101A (en) | 2017-04-30 |
| BR112014009282B1 (pt) | 2021-12-14 |
| IL232101A0 (en) | 2014-05-28 |
| WO2013059194A1 (en) | 2013-04-25 |
| US9499511B2 (en) | 2016-11-22 |
| KR20140107197A (ko) | 2014-09-04 |
| HK1200168A1 (en) | 2015-07-31 |
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