ES2393049T3 - Compuestos donantes de óxido nítrico - Google Patents
Compuestos donantes de óxido nítrico Download PDFInfo
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- ES2393049T3 ES2393049T3 ES09708682T ES09708682T ES2393049T3 ES 2393049 T3 ES2393049 T3 ES 2393049T3 ES 09708682 T ES09708682 T ES 09708682T ES 09708682 T ES09708682 T ES 09708682T ES 2393049 T3 ES2393049 T3 ES 2393049T3
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 143
- 239000002840 nitric oxide donor Substances 0.000 title description 9
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 229910004679 ONO2 Inorganic materials 0.000 claims abstract description 15
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 6
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims abstract description 3
- 125000003837 (C1-C20) alkyl group Chemical group 0.000 claims abstract description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- 201000010099 disease Diseases 0.000 claims description 14
- 125000001893 nitrooxy group Chemical group [O-][N+](=O)O* 0.000 claims description 12
- 208000017169 kidney disease Diseases 0.000 claims description 11
- 206010020772 Hypertension Diseases 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 238000011282 treatment Methods 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 6
- 208000002193 Pain Diseases 0.000 claims description 6
- 206010012601 diabetes mellitus Diseases 0.000 claims description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
- 208000035473 Communicable disease Diseases 0.000 claims description 5
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 5
- 208000010412 Glaucoma Diseases 0.000 claims description 5
- 206010061218 Inflammation Diseases 0.000 claims description 5
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 5
- 206010030043 Ocular hypertension Diseases 0.000 claims description 5
- 206010037660 Pyrexia Diseases 0.000 claims description 5
- 208000022901 Reynold syndrome Diseases 0.000 claims description 5
- 206010039710 Scleroderma Diseases 0.000 claims description 5
- 201000001880 Sexual dysfunction Diseases 0.000 claims description 5
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 5
- 230000002159 abnormal effect Effects 0.000 claims description 5
- 230000004097 bone metabolism Effects 0.000 claims description 5
- 210000003169 central nervous system Anatomy 0.000 claims description 5
- 230000004064 dysfunction Effects 0.000 claims description 5
- 208000026278 immune system disease Diseases 0.000 claims description 5
- 230000004054 inflammatory process Effects 0.000 claims description 5
- 230000005764 inhibitory process Effects 0.000 claims description 5
- 208000019423 liver disease Diseases 0.000 claims description 5
- 201000006938 muscular dystrophy Diseases 0.000 claims description 5
- 230000001575 pathological effect Effects 0.000 claims description 5
- 210000001428 peripheral nervous system Anatomy 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 208000023504 respiratory system disease Diseases 0.000 claims description 5
- 231100000872 sexual dysfunction Toxicity 0.000 claims description 5
- 208000010110 spontaneous platelet aggregation Diseases 0.000 claims description 5
- 239000005541 ACE inhibitor Substances 0.000 claims description 4
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 4
- 239000000048 adrenergic agonist Substances 0.000 claims description 4
- 229940126157 adrenergic receptor agonist Drugs 0.000 claims description 4
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims description 4
- 229940124599 anti-inflammatory drug Drugs 0.000 claims description 4
- 229940127217 antithrombotic drug Drugs 0.000 claims description 4
- 230000004663 cell proliferation Effects 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 4
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 4
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 4
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 4
- 229940094443 oxytocics prostaglandins Drugs 0.000 claims description 4
- 150000003180 prostaglandins Chemical class 0.000 claims description 4
- 230000003637 steroidlike Effects 0.000 claims description 4
- 229940124597 therapeutic agent Drugs 0.000 claims description 4
- 208000019553 vascular disease Diseases 0.000 claims description 4
- 125000006832 (C1-C10) alkylene group Chemical group 0.000 claims description 3
- 239000002333 angiotensin II receptor antagonist Substances 0.000 claims description 3
- 229940126317 angiotensin II receptor antagonist Drugs 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 102000005962 receptors Human genes 0.000 claims description 3
- 108020003175 receptors Proteins 0.000 claims description 3
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 208000035475 disorder Diseases 0.000 claims 1
- 230000000626 neurodegenerative effect Effects 0.000 claims 1
- 229940124531 pharmaceutical excipient Drugs 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 66
- 239000000243 solution Substances 0.000 description 48
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 47
- 239000000203 mixture Substances 0.000 description 42
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 34
- 238000000034 method Methods 0.000 description 33
- 235000019439 ethyl acetate Nutrition 0.000 description 32
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 22
- 238000003818 flash chromatography Methods 0.000 description 22
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 22
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 17
- 229910052938 sodium sulfate Inorganic materials 0.000 description 17
- 235000011152 sodium sulphate Nutrition 0.000 description 17
- 239000012074 organic phase Substances 0.000 description 16
- 238000005160 1H NMR spectroscopy Methods 0.000 description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
- -1 exyl Chemical group 0.000 description 12
- 239000000047 product Substances 0.000 description 11
- 239000002243 precursor Substances 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 125000006239 protecting group Chemical group 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- 239000003981 vehicle Substances 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- 150000007529 inorganic bases Chemical class 0.000 description 8
- ITHMZXMFOKWUTQ-UHFFFAOYSA-N nitro hexaneperoxoate Chemical compound CCCCCC(=O)OO[N+]([O-])=O ITHMZXMFOKWUTQ-UHFFFAOYSA-N 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 150000007530 organic bases Chemical class 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 235000019799 monosodium phosphate Nutrition 0.000 description 7
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- KLDXJTOLSGUMSJ-KVTDHHQDSA-N (3r,3ar,6r,6ar)-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3,6-diol Chemical compound O[C@@H]1CO[C@@H]2[C@H](O)CO[C@@H]21 KLDXJTOLSGUMSJ-KVTDHHQDSA-N 0.000 description 6
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 6
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- XEYBHCRIKKKOSS-UHFFFAOYSA-N disodium;azanylidyneoxidanium;iron(2+);pentacyanide Chemical compound [Na+].[Na+].[Fe+2].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].[O+]#N XEYBHCRIKKKOSS-UHFFFAOYSA-N 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 229910001961 silver nitrate Inorganic materials 0.000 description 5
- 229940083618 sodium nitroprusside Drugs 0.000 description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 229910002651 NO3 Inorganic materials 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 4
- 229960004373 acetylcholine Drugs 0.000 description 4
- 239000000010 aprotic solvent Substances 0.000 description 4
- 230000036772 blood pressure Effects 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 230000008602 contraction Effects 0.000 description 4
- XUDOZULIAWNMIU-UHFFFAOYSA-N delta-hexenoic acid Chemical compound OC(=O)CCCC=C XUDOZULIAWNMIU-UHFFFAOYSA-N 0.000 description 4
- MQYQOVYIJOLTNX-UHFFFAOYSA-N dichloromethane;n,n-dimethylformamide Chemical compound ClCCl.CN(C)C=O MQYQOVYIJOLTNX-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 4
- WCJMWGWSDDVBOJ-YFKPBYRVSA-N (5s)-5-nitrooxyhexanoic acid Chemical compound [O-][N+](=O)O[C@@H](C)CCCC(O)=O WCJMWGWSDDVBOJ-YFKPBYRVSA-N 0.000 description 3
- ZIIQCSMRQKCOCT-UHFFFAOYSA-N 2-acetamido-3-methyl-3-nitrososulfanylbutanoic acid Chemical compound CC(=O)NC(C(O)=O)C(C)(C)SN=O ZIIQCSMRQKCOCT-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 206010002383 Angina Pectoris Diseases 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 239000012445 acidic reagent Substances 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 239000003701 inert diluent Substances 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 229960003827 isosorbide mononitrate Drugs 0.000 description 3
- YWXYYJSYQOXTPL-SLPGGIOYSA-N isosorbide mononitrate Chemical compound [O-][N+](=O)O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 YWXYYJSYQOXTPL-SLPGGIOYSA-N 0.000 description 3
- 230000000802 nitrating effect Effects 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 230000002035 prolonged effect Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 230000035488 systolic blood pressure Effects 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 2
- ANRWNFAYJJPIKT-UHFFFAOYSA-N (3,3-dimethyl-5,6-dinitrooxyhexyl) 4-nitrobenzoate Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CC(C)(C)CCOC(=O)C1=CC=C([N+]([O-])=O)C=C1 ANRWNFAYJJPIKT-UHFFFAOYSA-N 0.000 description 2
- LOVPHSMOAVXQIH-UHFFFAOYSA-N (4-nitrophenyl) hydrogen carbonate Chemical compound OC(=O)OC1=CC=C([N+]([O-])=O)C=C1 LOVPHSMOAVXQIH-UHFFFAOYSA-N 0.000 description 2
- BQLNOTPAELUOHK-YFKPBYRVSA-N (5s)-5,6-dinitrooxyhexanoic acid Chemical group OC(=O)CCC[C@H](O[N+]([O-])=O)CO[N+]([O-])=O BQLNOTPAELUOHK-YFKPBYRVSA-N 0.000 description 2
- PAJXKWOLMFXETC-UHFFFAOYSA-N (6-hydroxy-4,4-dimethyl-1-nitrooxyhexan-2-yl) nitrate Chemical compound OCCC(C)(C)CC(O[N+]([O-])=O)CO[N+]([O-])=O PAJXKWOLMFXETC-UHFFFAOYSA-N 0.000 description 2
- QYZBMMOLPVKAPU-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl nitrate Chemical compound OCC(CO)O[N+]([O-])=O QYZBMMOLPVKAPU-UHFFFAOYSA-N 0.000 description 2
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 2
- HXWLJBVVXXBZCM-UHFFFAOYSA-N 2,3-dihydroxypropyl nitrate Chemical compound OCC(O)CO[N+]([O-])=O HXWLJBVVXXBZCM-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 2
- LGCBVEQNSDSLIH-UHFFFAOYSA-N 4-pyridin-3-ylbutanal Chemical compound O=CCCCC1=CC=CN=C1 LGCBVEQNSDSLIH-UHFFFAOYSA-N 0.000 description 2
- JNTPTNNCGDAGEJ-UHFFFAOYSA-N 6-chlorohexan-1-ol Chemical compound OCCCCCCCl JNTPTNNCGDAGEJ-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 244000025254 Cannabis sativa Species 0.000 description 2
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- KCWZGJVSDFYRIX-YFKPBYRVSA-N N(gamma)-nitro-L-arginine methyl ester Chemical compound COC(=O)[C@@H](N)CCCN=C(N)N[N+]([O-])=O KCWZGJVSDFYRIX-YFKPBYRVSA-N 0.000 description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- IIWWWHLFCFUKJV-AMOVGVPESA-N [(3r,3ar,6r,6ar)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl] (5s)-5-nitrooxyhexanoate Chemical compound O[C@@H]1CO[C@@H]2[C@H](OC(=O)CCC[C@H](C)O[N+]([O-])=O)CO[C@@H]21 IIWWWHLFCFUKJV-AMOVGVPESA-N 0.000 description 2
- FQTGYQKXWLOIEK-WNRNVDISSA-N [(3s,3ar,6s,6ar)-6-benzoyloxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-yl] benzoate Chemical compound O([C@@H]1[C@H]2OC[C@@H]([C@H]2OC1)OC(=O)C=1C=CC=CC=1)C(=O)C1=CC=CC=C1 FQTGYQKXWLOIEK-WNRNVDISSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 125000005529 alkyleneoxy group Chemical group 0.000 description 2
- 239000002249 anxiolytic agent Substances 0.000 description 2
- 210000000709 aorta Anatomy 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 210000003038 endothelium Anatomy 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
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- 231100000344 non-irritating Toxicity 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 238000006303 photolysis reaction Methods 0.000 description 1
- 230000015843 photosynthesis, light reaction Effects 0.000 description 1
- UBDXVNAAGCHEIC-UHFFFAOYSA-N piperidin-4-yl nitrate;hydrochloride Chemical compound Cl.[O-][N+](=O)OC1CCNCC1 UBDXVNAAGCHEIC-UHFFFAOYSA-N 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 210000002254 renal artery Anatomy 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 235000011044 succinic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid group Chemical group C(CCC(=O)O)(=O)O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- PWQLFIKTGRINFF-UHFFFAOYSA-N tert-butyl 4-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(O)CC1 PWQLFIKTGRINFF-UHFFFAOYSA-N 0.000 description 1
- BWXBHTGSZFJVTC-UHFFFAOYSA-N tert-butyl 4-nitrooxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(O[N+]([O-])=O)CC1 BWXBHTGSZFJVTC-UHFFFAOYSA-N 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- AWLILQARPMWUHA-UHFFFAOYSA-M thiopental sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC([S-])=NC1=O AWLILQARPMWUHA-UHFFFAOYSA-M 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000006442 vascular tone Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A—HUMAN NECESSITIES
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- 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
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A—HUMAN NECESSITIES
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- 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
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
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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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- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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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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- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A—HUMAN NECESSITIES
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- A61P27/06—Antiglaucoma agents or miotics
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P37/02—Immunomodulators
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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- A—HUMAN NECESSITIES
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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
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Neurology (AREA)
- Physical Education & Sports Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Cardiology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Rheumatology (AREA)
- Obesity (AREA)
- Immunology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Endocrinology (AREA)
- Urology & Nephrology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Pulmonology (AREA)
- Dermatology (AREA)
- Gastroenterology & Hepatology (AREA)
- Emergency Medicine (AREA)
- Vascular Medicine (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US694608P | 2008-02-07 | 2008-02-07 | |
| US6946P | 2008-02-07 | ||
| PCT/EP2009/050416 WO2009098113A1 (en) | 2008-02-07 | 2009-01-15 | Nitric oxide donor compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2393049T3 true ES2393049T3 (es) | 2012-12-18 |
Family
ID=40445685
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES09708682T Active ES2393049T3 (es) | 2008-02-07 | 2009-01-15 | Compuestos donantes de óxido nítrico |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US8003811B2 (https=) |
| EP (1) | EP2238143B1 (https=) |
| JP (1) | JP5441928B2 (https=) |
| CA (1) | CA2706082C (https=) |
| ES (1) | ES2393049T3 (https=) |
| WO (1) | WO2009098113A1 (https=) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2731298T3 (es) | 2005-05-27 | 2019-11-14 | Univ North Carolina Chapel Hill | Partículas de liberación de óxido nítrico para agentes terapéuticos de óxido nítrico y aplicaciones biomédicas |
| WO2011022652A1 (en) | 2009-08-21 | 2011-02-24 | Novan, Inc. | Topical gels |
| CA2771389C (en) | 2009-08-21 | 2019-04-09 | Novan, Inc. | Wound dressings, methods of using the same and methods of forming the same |
| KR101794363B1 (ko) | 2009-12-11 | 2017-11-06 | 디에스엠 아이피 어셋츠 비.브이. | 반추동물에서의 메탄 방출을 감소시키고/감소시키거나 반추동물 수익성을 개선시키기 위한 사료중의 니트로옥시 알칸산 및 이의 유도체 |
| US8591876B2 (en) | 2010-12-15 | 2013-11-26 | Novan, Inc. | Methods of decreasing sebum production in the skin |
| WO2012118829A2 (en) | 2011-02-28 | 2012-09-07 | Novan, Inc. | Tertiary s-nitrosothiol-modified nitricoxide-releasing xerogels and methods of using the same |
| US10154981B2 (en) | 2011-05-26 | 2018-12-18 | Dsm Ip Assets B.V. | Use of a feed composition for reducing methane emission in ruminants, and/or to improve ruminant performance |
| CN105026402A (zh) * | 2013-03-05 | 2015-11-04 | 阿彻丹尼尔斯米德兰德公司 | 异己糖醇单三氟甲磺酸酯及其合成方法 |
| EP2986288B1 (en) * | 2013-04-18 | 2017-04-12 | Nicox Science Ireland | Quinone based nitric oxide donating compounds for ophthalmic use |
| WO2016022944A1 (en) * | 2014-08-08 | 2016-02-11 | Central Michigan University | Flame retardants from renewable resources |
| US10610509B2 (en) | 2014-11-19 | 2020-04-07 | Nicox S.A. | Combinations of prostaglandins and nitric oxide donors |
| EP3088388A1 (en) | 2015-04-30 | 2016-11-02 | NicOx S.A. | Nitric oxide donating derivatives of prostaglandins |
| WO2018224419A1 (en) | 2017-06-06 | 2018-12-13 | Nicox S.A. | Nitric oxide donating isomannide derivatives |
| JP7596257B2 (ja) | 2018-08-06 | 2024-12-09 | ニコックス エス．エー． | 一酸化窒素放出性ホスホジエステラーゼ５型阻害薬 |
| US11779560B2 (en) * | 2020-03-28 | 2023-10-10 | Coeurative, Inc. | Methods of using nitric oxide donor compounds for treatment of COVID-19 and other infectious diseases |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS60149521A (ja) * | 1984-01-18 | 1985-08-07 | Eisai Co Ltd | 高眼圧・緑内障治療・予防用点眼剤 |
| DE3831949A1 (de) | 1988-09-20 | 1990-03-22 | Mack Chem Pharm | Arzneimittel |
| ES2142773B1 (es) * | 1998-10-07 | 2001-01-01 | Lacer Sa | Derivados de mononitrato de isosorbida y su empleo como agentes vasodilatadores con tolerancia desminuida. |
| EP1336602A1 (en) * | 2002-02-13 | 2003-08-20 | Giovanni Scaramuzzino | Nitrate prodrugs able to release nitric oxide in a controlled and selective way and their use for prevention and treatment of inflammatory, ischemic and proliferative diseases |
| ES2258365B1 (es) * | 2003-10-03 | 2007-12-01 | Lacer, S.A. | Derivados de disulfuro, sulfuro, sulfoxido y sulfona de azucares ciclicos y sus usos. |
| IE20070934A1 (en) * | 2007-12-21 | 2009-06-24 | Trinity College Dublin | Efficient aspirin prodrugs |
-
2009
- 2009-01-15 ES ES09708682T patent/ES2393049T3/es active Active
- 2009-01-15 EP EP09708682A patent/EP2238143B1/en not_active Not-in-force
- 2009-01-15 US US12/744,168 patent/US8003811B2/en active Active
- 2009-01-15 JP JP2010545422A patent/JP5441928B2/ja not_active Expired - Fee Related
- 2009-01-15 CA CA2706082A patent/CA2706082C/en active Active
- 2009-01-15 WO PCT/EP2009/050416 patent/WO2009098113A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| US8003811B2 (en) | 2011-08-23 |
| US20100249189A1 (en) | 2010-09-30 |
| CA2706082C (en) | 2017-10-03 |
| EP2238143B1 (en) | 2012-08-15 |
| EP2238143A1 (en) | 2010-10-13 |
| CA2706082A1 (en) | 2009-08-13 |
| JP5441928B2 (ja) | 2014-03-12 |
| WO2009098113A1 (en) | 2009-08-13 |
| JP2011511022A (ja) | 2011-04-07 |
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