ES2611852T3 - Donadores de nitroxilo para el tratamiento de la hipertensión pulmonar - Google Patents
Donadores de nitroxilo para el tratamiento de la hipertensión pulmonar Download PDFInfo
- Publication number
- ES2611852T3 ES2611852T3 ES10784416.9T ES10784416T ES2611852T3 ES 2611852 T3 ES2611852 T3 ES 2611852T3 ES 10784416 T ES10784416 T ES 10784416T ES 2611852 T3 ES2611852 T3 ES 2611852T3
- Authority
- ES
- Spain
- Prior art keywords
- formula
- alkyl
- compound
- nitroxyl
- substituted
- 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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- ODUCDPQEXGNKDN-UHFFFAOYSA-N nitroxyl Chemical compound O=N ODUCDPQEXGNKDN-UHFFFAOYSA-N 0.000 title abstract description 34
- 208000002815 pulmonary hypertension Diseases 0.000 title abstract description 21
- 150000001875 compounds Chemical class 0.000 abstract description 66
- 125000000217 alkyl group Chemical group 0.000 abstract description 50
- -1 perhaloalkoxy Chemical group 0.000 abstract description 35
- 125000000592 heterocycloalkyl group Chemical group 0.000 abstract description 28
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract description 15
- 125000004093 cyano group Chemical group *C#N 0.000 abstract description 14
- 125000003545 alkoxy group Chemical group 0.000 abstract description 9
- 125000004390 alkyl sulfonyl group Chemical group 0.000 abstract description 8
- 125000003118 aryl group Chemical group 0.000 abstract description 8
- 238000000034 method Methods 0.000 abstract description 7
- 150000003839 salts Chemical class 0.000 abstract description 7
- 125000005163 aryl sulfanyl group Chemical group 0.000 abstract description 6
- 125000005135 aryl sulfinyl group Chemical group 0.000 abstract description 6
- 125000005171 cycloalkylsulfanyl group Chemical group 0.000 abstract description 6
- 125000004644 alkyl sulfinyl group Chemical group 0.000 abstract description 5
- 125000004414 alkyl thio group Chemical group 0.000 abstract description 5
- 125000004104 aryloxy group Chemical group 0.000 abstract description 5
- 125000000000 cycloalkoxy group Chemical group 0.000 abstract description 4
- 125000004663 dialkyl amino group Chemical group 0.000 abstract description 4
- 241000124008 Mammalia Species 0.000 abstract description 2
- 125000001475 halogen functional group Chemical group 0.000 abstract 1
- 125000000623 heterocyclic group Chemical group 0.000 description 31
- 125000005843 halogen group Chemical group 0.000 description 29
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 28
- 229910052757 nitrogen Inorganic materials 0.000 description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 17
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 17
- 229930192474 thiophene Natural products 0.000 description 14
- 229910003827 NRaRb Inorganic materials 0.000 description 13
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 13
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 229910052739 hydrogen Inorganic materials 0.000 description 12
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 12
- 229910052801 chlorine Inorganic materials 0.000 description 10
- 239000000460 chlorine Substances 0.000 description 10
- 239000001257 hydrogen Substances 0.000 description 10
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 10
- 125000000520 N-substituted aminocarbonyl group Chemical group [*]NC(=O)* 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 6
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 6
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 6
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 4
- 206010019280 Heart failures Diseases 0.000 description 4
- 208000014777 Pulmonary venoocclusive disease Diseases 0.000 description 4
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 4
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 4
- 125000002252 acyl group Chemical group 0.000 description 4
- 125000004442 acylamino group Chemical group 0.000 description 4
- 125000003710 aryl alkyl group Chemical group 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 4
- 125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 4
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 4
- 150000003852 triazoles Chemical class 0.000 description 4
- 229910006074 SO2NH2 Inorganic materials 0.000 description 3
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 125000001072 heteroaryl group Chemical group 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 3
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 3
- 125000001624 naphthyl group Chemical group 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- 230000002685 pulmonary effect Effects 0.000 description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 208000026151 Chronic thromboembolic pulmonary hypertension Diseases 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 208000019693 Lung disease Diseases 0.000 description 2
- 101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 description 2
- 208000031467 Pulmonary capillary hemangiomatosis Diseases 0.000 description 2
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 208000019622 heart disease Diseases 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 230000004962 physiological condition Effects 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 125000000547 substituted alkyl group Chemical group 0.000 description 2
- 125000005338 substituted cycloalkoxy group Chemical group 0.000 description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 2
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 1
- 102100025422 Bone morphogenetic protein receptor type-2 Human genes 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 208000002330 Congenital Heart Defects Diseases 0.000 description 1
- 208000003037 Diastolic Heart Failure Diseases 0.000 description 1
- 206010052337 Diastolic dysfunction Diseases 0.000 description 1
- 102000012085 Endoglin Human genes 0.000 description 1
- 108010036395 Endoglin Proteins 0.000 description 1
- 208000015872 Gaucher disease Diseases 0.000 description 1
- 101000934635 Homo sapiens Bone morphogenetic protein receptor type-2 Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010021133 Hypoventilation Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 208000020875 Idiopathic pulmonary arterial hypertension Diseases 0.000 description 1
- 208000024934 IgG4-related mediastinitis Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000029523 Interstitial Lung disease Diseases 0.000 description 1
- 206010049459 Lymphangioleiomyomatosis Diseases 0.000 description 1
- 101100490437 Mus musculus Acvrl1 gene Proteins 0.000 description 1
- 208000014767 Myeloproliferative disease Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000009905 Neurofibromatoses Diseases 0.000 description 1
- 206010061876 Obstruction Diseases 0.000 description 1
- BRMDATNYMUMZLN-UHFFFAOYSA-N Piloty's Acid Chemical compound ONS(=O)(=O)C1=CC=CC=C1 BRMDATNYMUMZLN-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000008253 Systolic Heart Failure Diseases 0.000 description 1
- 206010071436 Systolic dysfunction Diseases 0.000 description 1
- 208000024799 Thyroid disease Diseases 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 1
- 208000028831 congenital heart disease Diseases 0.000 description 1
- 208000018631 connective tissue disease Diseases 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 230000009547 development abnormality Effects 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 208000007345 glycogen storage disease Diseases 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 201000008298 histiocytosis Diseases 0.000 description 1
- 208000018875 hypoxemia Diseases 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 210000001821 langerhans cell Anatomy 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 201000004931 neurofibromatosis Diseases 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 230000005298 paramagnetic effect Effects 0.000 description 1
- 125000005010 perfluoroalkyl group Chemical group 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 208000007232 portal hypertension Diseases 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 210000001147 pulmonary artery Anatomy 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 201000004409 schistosomiasis Diseases 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010911 splenectomy Methods 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 238000001429 visible spectrum Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/18—Sulfonamides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pulmonology (AREA)
- Dermatology (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US26369809P | 2009-11-23 | 2009-11-23 | |
| US263698P | 2009-11-23 | ||
| US26412909P | 2009-11-24 | 2009-11-24 | |
| US264129P | 2009-11-24 | ||
| PCT/US2010/057844 WO2011063400A1 (en) | 2009-11-23 | 2010-11-23 | Nitroxyl donors for the treatment of pulmonary hypertension |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2611852T3 true ES2611852T3 (es) | 2017-05-10 |
Family
ID=43513876
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES10784416.9T Active ES2611852T3 (es) | 2009-11-23 | 2010-11-23 | Donadores de nitroxilo para el tratamiento de la hipertensión pulmonar |
Country Status (15)
| Country | Link |
|---|---|
| US (2) | US20110160200A1 (enExample) |
| EP (1) | EP2504003B1 (enExample) |
| JP (2) | JP2013511556A (enExample) |
| CY (1) | CY1118603T1 (enExample) |
| DK (1) | DK2504003T3 (enExample) |
| ES (1) | ES2611852T3 (enExample) |
| HR (1) | HRP20170183T1 (enExample) |
| HU (1) | HUE032253T2 (enExample) |
| LT (1) | LT2504003T (enExample) |
| PL (1) | PL2504003T3 (enExample) |
| PT (1) | PT2504003T (enExample) |
| RS (1) | RS55697B1 (enExample) |
| SI (1) | SI2504003T1 (enExample) |
| SM (2) | SMT201700090T1 (enExample) |
| WO (2) | WO2011063339A1 (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| AU2014267360B2 (en) * | 2013-05-14 | 2018-07-05 | Active Biotech Ab | N-(heteroaryl)-sulfonamide derivatives useful as S100-inhibitors |
| 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 |
| US9464061B2 (en) | 2014-05-27 | 2016-10-11 | The Johns Hopkins University | N-hydroxylamino-barbituric acid derivatives |
| 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 |
Family Cites Families (59)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3219428A (en) * | 1961-04-17 | 1965-11-23 | Hooker Chemical Corp | O,n-diacylated-3,4-dihalophenylhydroxylamines as herbicides |
| US3382243A (en) * | 1965-05-17 | 1968-05-07 | American Home Prod | Acetamides and their preparation |
| US3948967A (en) * | 1968-01-03 | 1976-04-06 | Velsicol Chemical Corporation | Aryl urea carbonates |
| US3661944A (en) * | 1970-07-01 | 1972-05-09 | Smith Kline French Lab | 4-(n-lower alkanoyl)hydroxylamino-4'-aminodiphenylsulfone compounds |
| US3746727A (en) * | 1971-06-07 | 1973-07-17 | Shell Oil Co | Benzenesulfhydroxamic acids and their derivatives |
| 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 |
| US4405357A (en) * | 1980-06-02 | 1983-09-20 | Fmc Corporation | Herbicidal 3-isoxazolidinones and hydroxamic acids |
| 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 |
| US4954526A (en) * | 1989-02-28 | 1990-09-04 | The United States Of America As Represented By The Department Of Health And Human Services | Stabilized nitric oxide - primary amine complexes useful as cardiovascular agents |
| US5039705A (en) * | 1989-09-15 | 1991-08-13 | The United States Of America As Represented By The Department Of Health And Human Services | Anti-hypertensive compositions of secondary amine-nitric oxide adducts and use thereof |
| US5721365A (en) * | 1989-09-15 | 1998-02-24 | Us Health | N-substituted piperazine NONOates |
| US5212204A (en) * | 1989-10-18 | 1993-05-18 | The United States Of America As Represented By The Department Of Health And Human Services | Antihypertensive compositions and use thereof |
| 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 |
| EP0604525A1 (en) * | 1991-09-20 | 1994-07-06 | Zeneca Limited | Enzymatic production of optical isomers of tetrahydropyran-2-ones |
| ES2112332T3 (es) * | 1991-09-24 | 1998-04-01 | Us Health | Derivados de substitucion de oxigeno de productos de adicion de nucleofilo-oxido nitrico utilizados como promedicamentos donadores de oxido nitrico. |
| US5814666A (en) * | 1992-04-13 | 1998-09-29 | The United States As Represented By The Department Of Health And Human Services | Encapsulated and non-encapsulated nitric oxide generators used as antimicrobial agents |
| US5278192A (en) * | 1992-07-02 | 1994-01-11 | The Research Foundation Of State University Of New York | Method of vasodilator therapy for treating a patient with a condition |
| US6200558B1 (en) * | 1993-09-14 | 2001-03-13 | The United States Of America As Represented By The Department Of Health And Human Services | Biopolymer-bound nitric oxide-releasing compositions, pharmaceutical compositions incorporating same and methods of treating biological disorders using same |
| DK0703902T3 (da) * | 1993-06-24 | 1999-08-23 | Albany Molecular Res Inc | Fremgangsmåde til fremstilling af piperidinderivater |
| JPH09508097A (ja) * | 1993-11-02 | 1997-08-19 | アメリカ合衆国 | 虚血再灌流傷害における保護剤としての酸化窒素放出化合物の使用 |
| US5700830A (en) * | 1994-11-22 | 1997-12-23 | The United States Of America As Represented By The Department Of Health And Human Services | Use of nitric oxide-releasing agents for reducing metastasis risk |
| US6043232A (en) * | 1997-07-23 | 2000-03-28 | Nitromed, Inc. | Nitroso esters of beta-oxo-amides and aryl propionic acid derivatives of non-steroidal antiinflammatory drugs |
| US5703073A (en) * | 1995-04-19 | 1997-12-30 | Nitromed, Inc. | Compositions and methods to prevent toxicity induced by nonsteroidal antiinflammatory drugs |
| US5674894A (en) * | 1995-05-15 | 1997-10-07 | G.D. Searle & Co. | Amidine derivatives useful as platelet aggregation inhibitors and vasodilators |
| US5714511A (en) * | 1995-07-31 | 1998-02-03 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Selective prevention of organ injury in sepsis and shock using selection release of nitric oxide in vulnerable organs |
| DE19545878A1 (de) * | 1995-12-08 | 1997-06-12 | Basf Ag | Pyridylcarbamate, Verfahren und Zwischenprodukte zu ihrer Herstellung und ihre Verwendung |
| US5824669A (en) * | 1996-03-22 | 1998-10-20 | Nitromed, Inc. | Nitrosated and nitrosylated compounds and compositions and their use for treating respiratory disorders |
| US5958427A (en) * | 1996-11-08 | 1999-09-28 | Salzman; Andrew L. | Nitric oxide donor compounds and pharmaceutical compositions for pulmonary hypertension and other indications |
| TW453999B (en) * | 1997-06-27 | 2001-09-11 | Fujisawa Pharmaceutical Co | Benzimidazole derivatives |
| WO1999021844A1 (en) * | 1997-10-24 | 1999-05-06 | Shionogi & Co., Ltd. | Antirheumatic |
| US6596705B1 (en) * | 1998-02-09 | 2003-07-22 | The Regents Of The University Of California | Inhibition of L-selectin and P-selection mediated binding using heparin |
| 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 |
| WO2000025776A1 (en) * | 1998-10-30 | 2000-05-11 | Nitromed, Inc. | Nitrosated and nitrosylated nonsteroidal antiinflammatory compounds, compositions and methods of use |
| IL148127A0 (en) * | 1999-08-30 | 2002-09-12 | Aventis Pharma Gmbh | Use of inhibitors of the renin-angiotensin system in the prevention of cardiovascular events |
| US7045152B2 (en) * | 1999-09-08 | 2006-05-16 | Duke University | Treating pulmonary disorders with gaseous agent causing repletion of GSNO |
| US20010053795A1 (en) * | 2000-06-20 | 2001-12-20 | Bond Richard A. | Paradoxical pharmacology |
| EP1301500B1 (en) * | 2000-06-22 | 2007-11-21 | Nitromed, Inc. | Nitrosated and nitrosylated taxanes, compositions and methods of use |
| US6706724B2 (en) * | 2000-12-21 | 2004-03-16 | Nitromed, Inc. | Substituted aryl compounds as novel cyclooxygenase-2 selective inhibitors, compositions and methods of use |
| WO2003006427A1 (en) * | 2001-07-12 | 2003-01-23 | Johns Hopkins University | Compounds that release nitric oxide at controlled rates upon photolysis |
| FR2832634A1 (fr) * | 2001-11-29 | 2003-05-30 | Univ Pasteur | Utilisation des isomeres l de derives aminoacides de l'hydroxyguanidine pour la production de no, compositions pharmaceutiques les contenant et utilisations pharmaceutiques |
| 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 |
| US20040077691A1 (en) * | 2002-06-21 | 2004-04-22 | Medinox, Inc. | Hydroxamate derivatives of non-steroidal anti-inflammatory drugs |
| 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 |
| US20050009789A1 (en) * | 2003-05-13 | 2005-01-13 | The Government Of The Usa As Represented By The Secretary Of The Dept. Of Health And Human Service | Cyclooxygenase inhibition with nitroxyl |
| 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 |
| JP2008543947A (ja) * | 2005-06-23 | 2008-12-04 | ジョンズ ホプキンス ユニバーシティ | チオール感受性の正の変力物質 |
| WO2007045962A2 (en) * | 2005-10-18 | 2007-04-26 | Orchid Research Laboratories Limited | Novel hdac inhibitors |
| PL2489350T3 (pl) * | 2006-03-17 | 2014-08-29 | Cardioxyl Pharmaceuticals Inc | Pochodne N-hydroksylosulfonamidu jako nowe, fizjologicznie użyteczne donory nitroksylu |
| 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 |
| CA2782110A1 (en) * | 2009-12-07 | 2011-06-16 | Johns Hopkins University | N-acyloxysulfonamide and n-hydroxy-n-acylsulfonamide derivatives |
| 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 |
-
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- 2010-11-22 US US12/951,900 patent/US20110160200A1/en not_active Abandoned
- 2010-11-23 PT PT107844169T patent/PT2504003T/pt unknown
- 2010-11-23 EP EP10784416.9A patent/EP2504003B1/en active Active
- 2010-11-23 ES ES10784416.9T patent/ES2611852T3/es active Active
- 2010-11-23 WO PCT/US2010/057844 patent/WO2011063400A1/en not_active Ceased
- 2010-11-23 JP JP2012540154A patent/JP2013511556A/ja active Pending
- 2010-11-23 DK DK10784416.9T patent/DK2504003T3/en active
- 2010-11-23 SM SM20170090T patent/SMT201700090T1/it unknown
- 2010-11-23 PL PL10784416T patent/PL2504003T3/pl unknown
- 2010-11-23 HU HUE10784416A patent/HUE032253T2/en unknown
- 2010-11-23 SI SI201031332A patent/SI2504003T1/sl unknown
- 2010-11-23 LT LTEP10784416.9T patent/LT2504003T/lt unknown
- 2010-11-23 RS RS20170138A patent/RS55697B1/sr unknown
- 2010-11-23 HR HRP20170183TT patent/HRP20170183T1/hr unknown
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2015
- 2015-04-24 US US14/696,319 patent/US20160081951A1/en not_active Abandoned
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2016
- 2016-01-29 JP JP2016015102A patent/JP2016128481A/ja active Pending
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2017
- 2017-02-07 CY CY20171100169T patent/CY1118603T1/el unknown
- 2017-02-09 SM SM201700090T patent/SMT201700090B/it unknown
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| CY1118603T1 (el) | 2017-07-12 |
| JP2016128481A (ja) | 2016-07-14 |
| WO2011063339A1 (en) | 2011-05-26 |
| US20110160200A1 (en) | 2011-06-30 |
| EP2504003A1 (en) | 2012-10-03 |
| US20160081951A1 (en) | 2016-03-24 |
| SMT201700090T1 (it) | 2017-03-08 |
| HUE032253T2 (en) | 2017-09-28 |
| LT2504003T (lt) | 2017-01-25 |
| SMT201700090B (it) | 2017-03-08 |
| DK2504003T3 (en) | 2017-02-20 |
| EP2504003B1 (en) | 2016-11-09 |
| RS55697B1 (sr) | 2017-07-31 |
| JP2013511556A (ja) | 2013-04-04 |
| WO2011063400A1 (en) | 2011-05-26 |
| SI2504003T1 (sl) | 2017-01-31 |
| PL2504003T3 (pl) | 2017-04-28 |
| HRP20170183T1 (hr) | 2017-03-24 |
| PT2504003T (pt) | 2017-01-31 |
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