JP5441928B2 - 一酸化窒素供与化合物 - Google Patents
一酸化窒素供与化合物 Download PDFInfo
- Publication number
- JP5441928B2 JP5441928B2 JP2010545422A JP2010545422A JP5441928B2 JP 5441928 B2 JP5441928 B2 JP 5441928B2 JP 2010545422 A JP2010545422 A JP 2010545422A JP 2010545422 A JP2010545422 A JP 2010545422A JP 5441928 B2 JP5441928 B2 JP 5441928B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- formula
- group
- mmol
- ono
- 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.)
- Expired - Fee Related
Links
- 150000001875 compounds Chemical class 0.000 title claims description 139
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 title description 5
- 150000003839 salts Chemical class 0.000 claims description 17
- CHNUOJQWGUIOLD-NFZZJPOKSA-N epalrestat Chemical group C=1C=CC=CC=1\C=C(/C)\C=C1/SC(=S)N(CC(O)=O)C1=O CHNUOJQWGUIOLD-NFZZJPOKSA-N 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 9
- 238000011282 treatment Methods 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 206010020772 Hypertension Diseases 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 208000024172 Cardiovascular disease 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
- 239000000808 adrenergic beta-agonist Substances 0.000 claims description 4
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims description 4
- 239000003146 anticoagulant agent Substances 0.000 claims description 4
- 229960004676 antithrombotic agent Drugs 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 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
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 150000003180 prostaglandins Chemical class 0.000 claims description 4
- 229940124597 therapeutic agent Drugs 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
- 102000012740 beta Adrenergic Receptors Human genes 0.000 claims description 3
- 108010079452 beta Adrenergic Receptors Proteins 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 2
- 229940094443 oxytocics prostaglandins Drugs 0.000 claims description 2
- 239000002246 antineoplastic agent Substances 0.000 claims 1
- 230000002757 inflammatory effect Effects 0.000 claims 1
- 230000003637 steroidlike Effects 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 50
- 239000000203 mixture Substances 0.000 description 39
- 239000000243 solution Substances 0.000 description 38
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 36
- 238000000034 method Methods 0.000 description 30
- 235000019439 ethyl acetate Nutrition 0.000 description 24
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 20
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 238000003818 flash chromatography Methods 0.000 description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 14
- 0 *[C@](CO[C@@]12)[C@]1OCC2=* Chemical compound *[C@](CO[C@@]12)[C@]1OCC2=* 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
- 238000005481 NMR spectroscopy Methods 0.000 description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
- 239000012044 organic layer Substances 0.000 description 12
- 229910052938 sodium sulfate Inorganic materials 0.000 description 12
- 235000011152 sodium sulphate Nutrition 0.000 description 12
- 125000006239 protecting group Chemical group 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000002243 precursor Substances 0.000 description 9
- 239000011541 reaction mixture 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
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- -1 diazeniumdiolate ions Chemical class 0.000 description 7
- 150000007529 inorganic bases Chemical class 0.000 description 7
- 150000007530 organic bases Chemical class 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- KLDXJTOLSGUMSJ-UNTFVMJOSA-N (3s,3ar,6s,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-UNTFVMJOSA-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
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 6
- 208000017169 kidney disease Diseases 0.000 description 6
- 239000002840 nitric oxide donor Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 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 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 229910002651 NO3 Inorganic materials 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 5
- 235000019799 monosodium phosphate Nutrition 0.000 description 5
- 229910001961 silver nitrate Inorganic materials 0.000 description 5
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 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 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- 101710134784 Agnoprotein Proteins 0.000 description 4
- 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
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 208000002193 Pain Diseases 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
- 229940079593 drug Drugs 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000012454 non-polar solvent Substances 0.000 description 4
- 239000002798 polar solvent Substances 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 230000035488 systolic blood pressure Effects 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 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
- 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 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
- 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 3
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 3
- 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 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
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 208000018522 Gastrointestinal disease Diseases 0.000 description 3
- 208000010412 Glaucoma Diseases 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 208000001145 Metabolic Syndrome Diseases 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
- 206010030043 Ocular hypertension Diseases 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 206010037660 Pyrexia Diseases 0.000 description 3
- 208000022901 Reynold syndrome Diseases 0.000 description 3
- 208000016717 Reynolds syndrome Diseases 0.000 description 3
- 206010039710 Scleroderma Diseases 0.000 description 3
- 201000001880 Sexual dysfunction Diseases 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- UPFGNEYGDINYKQ-DDHJBXDOSA-N [(3r,3ar,6r,6ar)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl] (4-nitrophenyl) carbonate Chemical compound O([C@H]1[C@H]2OC[C@H]([C@H]2OC1)O)C(=O)OC1=CC=C([N+]([O-])=O)C=C1 UPFGNEYGDINYKQ-DDHJBXDOSA-N 0.000 description 3
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 230000004663 cell proliferation Effects 0.000 description 3
- 208000015114 central nervous system disease Diseases 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 208000010643 digestive system disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 210000003038 endothelium Anatomy 0.000 description 3
- 208000030533 eye disease Diseases 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 208000018685 gastrointestinal system disease Diseases 0.000 description 3
- 208000026278 immune system disease Diseases 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 239000003701 inert diluent Substances 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 208000019423 liver disease Diseases 0.000 description 3
- 208000015122 neurodegenerative disease Diseases 0.000 description 3
- ITHMZXMFOKWUTQ-UHFFFAOYSA-N nitro hexaneperoxoate Chemical compound CCCCCC(=O)OO[N+]([O-])=O ITHMZXMFOKWUTQ-UHFFFAOYSA-N 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 208000027232 peripheral nervous system disease Diseases 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000003087 receptor blocking agent Substances 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 231100000872 sexual dysfunction Toxicity 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 3
- 239000002294 steroidal antiinflammatory agent Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 208000019553 vascular disease Diseases 0.000 description 3
- UORZWDQSXBGGOE-DDHJBXDOSA-N (3r,3ar,6r,6ar)-6-hex-5-enoxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound C=CCCCCO[C@@H]1CO[C@@H]2[C@H](O)CO[C@@H]21 UORZWDQSXBGGOE-DDHJBXDOSA-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
- 125000003161 (C1-C6) alkylene group Chemical group 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
- 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
- ZHEVXWBAPDRIKK-UHFFFAOYSA-N 3,3-dimethylhex-5-enyl 4-nitrobenzoate Chemical compound C=CCC(C)(C)CCOC(=O)C1=CC=C([N+]([O-])=O)C=C1 ZHEVXWBAPDRIKK-UHFFFAOYSA-N 0.000 description 2
- SNPDKBFMQHFHFY-UHFFFAOYSA-N 3-(2,3-dinitrooxypropoxy)propanoic acid Chemical compound OC(=O)CCOCC(O[N+]([O-])=O)CO[N+]([O-])=O SNPDKBFMQHFHFY-UHFFFAOYSA-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
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 239000012981 Hank's balanced salt solution Substances 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
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 102000007637 Soluble Guanylyl Cyclase Human genes 0.000 description 2
- 108010007205 Soluble Guanylyl Cyclase Proteins 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- KUVPCVSHHFFROJ-SFPZXJLLSA-N [(3r,3ar,6r,6ar)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl] (3,3-dimethyl-5,6-dinitrooxyhexyl) carbonate Chemical compound O[C@@H]1CO[C@@H]2[C@H](OC(=O)OCCC(C)(C)CC(CO[N+]([O-])=O)O[N+]([O-])=O)CO[C@@H]21 KUVPCVSHHFFROJ-SFPZXJLLSA-N 0.000 description 2
- ZKGFNQUBHZVIQK-GBLBWHTRSA-N [(3r,3ar,6r,6ar)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl] 3-(2,3-dinitrooxypropoxy)propanoate Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)COCCC(=O)O[C@@H]1CO[C@@H]2[C@H](O)CO[C@@H]21 ZKGFNQUBHZVIQK-GBLBWHTRSA-N 0.000 description 2
- HLBYTUKKFDKGBQ-GBLBWHTRSA-N [(3r,3ar,6r,6ar)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl] 5,6-dinitrooxyhexanoate Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CCCC(=O)O[C@@H]1CO[C@@H]2[C@H](O)CO[C@@H]21 HLBYTUKKFDKGBQ-GBLBWHTRSA-N 0.000 description 2
- MUVBTHMPGCEFEG-DDHJBXDOSA-N [(3r,3ar,6r,6ar)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl] 6-chlorohexyl carbonate Chemical compound ClCCCCCCOC(=O)O[C@@H]1CO[C@@H]2[C@H](O)CO[C@@H]21 MUVBTHMPGCEFEG-DDHJBXDOSA-N 0.000 description 2
- DZALPUURJGQZKG-CNVPUSNMSA-N [(3r,3ar,6r,6ar)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl] hex-5-enoate Chemical compound C=CCCCC(=O)O[C@@H]1CO[C@@H]2[C@H](O)CO[C@@H]21 DZALPUURJGQZKG-CNVPUSNMSA-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
- 229960004373 acetylcholine Drugs 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 229940126317 angiotensin II receptor antagonist Drugs 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 230000004097 bone metabolism Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- XUDOZULIAWNMIU-UHFFFAOYSA-N delta-hexenoic acid Chemical compound OC(=O)CCCC=C XUDOZULIAWNMIU-UHFFFAOYSA-N 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- XEYBHCRIKKKOSS-UHFFFAOYSA-N disodium;azanylidyneoxidanium;iron(2+);pentacyanide Chemical group [Na+].[Na+].[Fe+2].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].[O+]#N XEYBHCRIKKKOSS-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 229960003711 glyceryl trinitrate Drugs 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- QWXYZCJEXYQNEI-OSZHWHEXSA-N intermediate I Chemical compound COC(=O)[C@@]1(C=O)[C@H]2CC=[N+](C\C2=C\C)CCc2c1[nH]c1ccccc21 QWXYZCJEXYQNEI-OSZHWHEXSA-N 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 229960003827 isosorbide mononitrate Drugs 0.000 description 2
- 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 2
- 230000007774 longterm Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 201000006938 muscular dystrophy Diseases 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 238000006396 nitration reaction Methods 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 239000000346 nonvolatile oil Substances 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
- 208000023504 respiratory system disease Diseases 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
- 239000011780 sodium chloride Substances 0.000 description 2
- 229940083618 sodium nitroprusside Drugs 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 238000002636 symptomatic treatment Methods 0.000 description 2
- QOXLZBOULOLPGT-QMMMGPOBSA-N tert-butyl (5s)-5,6-dihydroxyhexanoate Chemical compound CC(C)(C)OC(=O)CCC[C@H](O)CO QOXLZBOULOLPGT-QMMMGPOBSA-N 0.000 description 2
- XNBBRQGAPIDYKF-UHFFFAOYSA-N tert-butyl hex-5-enoate Chemical compound CC(C)(C)OC(=O)CCCC=C XNBBRQGAPIDYKF-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 239000003071 vasodilator agent Substances 0.000 description 2
- 230000001196 vasorelaxation Effects 0.000 description 2
- 230000002883 vasorelaxation effect Effects 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- CNBHBZZWRUQPTN-XSCZHNOTSA-N (3s,3ar,6s,6ar)-6-(oxan-2-yloxy)-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3-ol Chemical compound O([C@@H]1[C@H]2OC[C@@H]([C@H]2OC1)O)C1CCCCO1 CNBHBZZWRUQPTN-XSCZHNOTSA-N 0.000 description 1
- JWEIRDQGGUBZPD-UHFFFAOYSA-N (4-nitrophenyl) 3-(2,3-dinitrooxypropoxy)propanoate Chemical group [O-][N+](=O)OCC(O[N+]([O-])=O)COCCC(=O)OC1=CC=C([N+]([O-])=O)C=C1 JWEIRDQGGUBZPD-UHFFFAOYSA-N 0.000 description 1
- NXLNNXIXOYSCMB-UHFFFAOYSA-N (4-nitrophenyl) carbonochloridate Chemical compound [O-][N+](=O)C1=CC=C(OC(Cl)=O)C=C1 NXLNNXIXOYSCMB-UHFFFAOYSA-N 0.000 description 1
- WCJMWGWSDDVBOJ-RXMQYKEDSA-N (5r)-5-nitrooxyhexanoic acid Chemical group [O-][N+](=O)O[C@H](C)CCCC(O)=O WCJMWGWSDDVBOJ-RXMQYKEDSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- HVHZEKKZMFRULH-UHFFFAOYSA-N 2,6-ditert-butyl-4-methylpyridine Chemical compound CC1=CC(C(C)(C)C)=NC(C(C)(C)C)=C1 HVHZEKKZMFRULH-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- OGBZELSUKYODHJ-UHFFFAOYSA-N 2-tert-butyl-4-methylpyridine Chemical compound CC1=CC=NC(C(C)(C)C)=C1 OGBZELSUKYODHJ-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- APIXJSLKIYYUKG-UHFFFAOYSA-N 3 Isobutyl 1 methylxanthine Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N=CN2 APIXJSLKIYYUKG-UHFFFAOYSA-N 0.000 description 1
- YUCBLVFHJWOYDN-PPIALRKJSA-N 4-[(r)-[(2r,4s,5r)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methoxy]-1-[(r)-[(2r,4r,5s)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methoxy]phthalazine Chemical compound C1=C(OC)C=C2C([C@@H](OC=3C4=CC=CC=C4C(O[C@@H]([C@@H]4N5CC[C@@H]([C@@H](C5)CC)C4)C=4C5=CC(OC)=CC=C5N=CC=4)=NN=3)[C@H]3C[C@@H]4CCN3C[C@@H]4CC)=CC=NC2=C1 YUCBLVFHJWOYDN-PPIALRKJSA-N 0.000 description 1
- RIMXEJYJXDBLIE-UHFFFAOYSA-N 6-bromohex-1-ene Chemical compound BrCCCCC=C RIMXEJYJXDBLIE-UHFFFAOYSA-N 0.000 description 1
- NVRVNSHHLPQGCU-UHFFFAOYSA-N 6-bromohexanoic acid Chemical compound OC(=O)CCCCCBr NVRVNSHHLPQGCU-UHFFFAOYSA-N 0.000 description 1
- JNTPTNNCGDAGEJ-UHFFFAOYSA-N 6-chlorohexan-1-ol Chemical compound OCCCCCCCl JNTPTNNCGDAGEJ-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 102000008873 Angiotensin II receptor Human genes 0.000 description 1
- 108050000824 Angiotensin II receptor Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- ATOAHNRJAXSBOR-UHFFFAOYSA-N BAY 41-2272 Chemical compound NC1=NC(C=2C3=CC=CN=C3N(CC=3C(=CC=CC=3)F)N=2)=NC=C1C1CC1 ATOAHNRJAXSBOR-UHFFFAOYSA-N 0.000 description 1
- 229940127280 BAY 41-2272 Drugs 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- RKFMWWNGNPRYFG-FYBJJZIISA-N C=[I][C@]([C@@H](CO1)O)(C11I)OC[C@H]1O Chemical compound C=[I][C@]([C@@H](CO1)O)(C11I)OC[C@H]1O RKFMWWNGNPRYFG-FYBJJZIISA-N 0.000 description 1
- POBADXVRSYPSJB-KVPKETBZSA-N C=[I][C@]1([C@@]2(C#[I])OC[C@@H]1O)OC[C@H]2O Chemical compound C=[I][C@]1([C@@]2(C#[I])OC[C@@H]1O)OC[C@H]2O POBADXVRSYPSJB-KVPKETBZSA-N 0.000 description 1
- WWHKLHQUVWAZHR-UHFFFAOYSA-N CCC1[O](C)CCC1O Chemical compound CCC1[O](C)CCC1O WWHKLHQUVWAZHR-UHFFFAOYSA-N 0.000 description 1
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 1
- HGBAJKXNBQUWSB-FSDSQADBSA-N C[C@H]1[C@H]2OCC[C@H]2OC1 Chemical compound C[C@H]1[C@H]2OCC[C@H]2OC1 HGBAJKXNBQUWSB-FSDSQADBSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical group C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 206010015719 Exsanguination Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010020802 Hypertensive crisis 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
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229940123921 Nitric oxide synthase inhibitor Drugs 0.000 description 1
- 239000000006 Nitroglycerin Substances 0.000 description 1
- PVGKHQRYYJYEKP-CNVPUSNMSA-N O[C@H](CO[C@@H]12)[C@H]1OC[C@H]2OC(CCCCCBr)=O Chemical compound O[C@H](CO[C@@H]12)[C@H]1OC[C@H]2OC(CCCCCBr)=O PVGKHQRYYJYEKP-CNVPUSNMSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 241000283977 Oryctolagus Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229940099471 Phosphodiesterase inhibitor Drugs 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 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 1
- HJTMTRXFSOATSJ-GWOFURMSSA-N [(3r,3ar,6r,6ar)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl] 4-nitrooxypiperidine-1-carboxylate Chemical compound O([C@H]1[C@H]2OC[C@H]([C@H]2OC1)O)C(=O)N1CCC(O[N+]([O-])=O)CC1 HJTMTRXFSOATSJ-GWOFURMSSA-N 0.000 description 1
- NOSIYYJFMPDDSA-UHFFFAOYSA-N acepromazine Chemical compound C1=C(C(C)=O)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 NOSIYYJFMPDDSA-UHFFFAOYSA-N 0.000 description 1
- 229960005054 acepromazine Drugs 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 125000005336 allyloxy group Chemical group 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 210000000702 aorta abdominal Anatomy 0.000 description 1
- 210000002376 aorta thoracic Anatomy 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229940087373 calcium oxide Drugs 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 238000007596 consolidation process Methods 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000035487 diastolic blood pressure Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000003126 guanylate cyclase inhibitor Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000003818 metabolic dysfunction Effects 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 125000005699 methyleneoxy group Chemical group [H]C([H])([*:1])O[*:2] 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000037023 motor activity Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 239000000236 nitric oxide synthase inhibitor Substances 0.000 description 1
- 150000002825 nitriles Chemical group 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 125000001893 nitrooxy group Chemical group [O-][N+](=O)O* 0.000 description 1
- 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
- 230000000269 nucleophilic effect Effects 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
- 239000012053 oil suspension Substances 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 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
- 235000006408 oxalic acid Nutrition 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
- 229910052760 oxygen Inorganic materials 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
- 238000006303 photolysis reaction Methods 0.000 description 1
- 230000015843 photosynthesis, light reaction Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 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
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000008569 process Effects 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
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 210000002254 renal artery Anatomy 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000012047 saturated solution Substances 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
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate 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
- 230000002269 spontaneous effect Effects 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
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 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
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- 230000006442 vascular tone Effects 0.000 description 1
- 229940124549 vasodilator Drugs 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
-
- 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
-
- 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
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- 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
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
-
- 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
- A61P9/10—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
-
- 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)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Physical Education & Sports Medicine (AREA)
- Neurology (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Ophthalmology & Optometry (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Endocrinology (AREA)
- Neurosurgery (AREA)
- Oncology (AREA)
- Vascular Medicine (AREA)
- Reproductive Health (AREA)
- Dermatology (AREA)
- Pulmonology (AREA)
- Emergency Medicine (AREA)
- Communicable Diseases (AREA)
- Gastroenterology & Hepatology (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 | |
| US61/006,946 | 2008-02-07 | ||
| PCT/EP2009/050416 WO2009098113A1 (en) | 2008-02-07 | 2009-01-15 | Nitric oxide donor compounds |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2011511022A JP2011511022A (ja) | 2011-04-07 |
| JP2011511022A5 JP2011511022A5 (cg-RX-API-DMAC7.html) | 2012-03-01 |
| JP5441928B2 true JP5441928B2 (ja) | 2014-03-12 |
Family
ID=40445685
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010545422A Expired - Fee Related JP5441928B2 (ja) | 2008-02-07 | 2009-01-15 | 一酸化窒素供与化合物 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US8003811B2 (cg-RX-API-DMAC7.html) |
| EP (1) | EP2238143B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP5441928B2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2706082C (cg-RX-API-DMAC7.html) |
| ES (1) | ES2393049T3 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2009098113A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2912259C (en) | 2005-05-27 | 2020-04-28 | Mark H. Schoenfisch | Nitric oxide-releasing particles for nitric oxide therapeutics and biomedical applications |
| CA2771389C (en) | 2009-08-21 | 2019-04-09 | Novan, Inc. | Wound dressings, methods of using the same and methods of forming the same |
| ES2958410T3 (es) | 2009-08-21 | 2024-02-08 | Novan Inc | Geles tópicos |
| CN102781252B (zh) * | 2009-12-11 | 2015-02-11 | 帝斯曼知识产权资产管理有限公司 | 饲料中用于减少反刍动物甲烷散发和/或改善反刍动物性能的硝基氧烷酸及其衍生物 |
| US8591876B2 (en) | 2010-12-15 | 2013-11-26 | Novan, Inc. | Methods of decreasing sebum production in the skin |
| ES2695173T3 (es) | 2011-02-28 | 2019-01-02 | Novan Inc | Partículas de sílice modificadas con S-nitrosotiol que liberan óxido nítrico y procedimientos de fabricación de las mismas |
| ES2547106T3 (es) * | 2011-05-26 | 2015-10-01 | Dsm Ip Assets B.V. | Uso de una composición de pienso para reducir la emisión de metano en rumiantes, y/o para mejorar el rendimiento de rumiantes |
| CA2902009A1 (en) * | 2013-03-05 | 2014-09-12 | Archer Daniels Midland Company | Isohexide monotriflates and process for synthesis thereof |
| WO2014170264A1 (en) * | 2013-04-18 | 2014-10-23 | Nicox Science Ireland | Quinone based nitric oxide donating compounds for ophthalmic use |
| US9738773B2 (en) * | 2014-08-08 | 2017-08-22 | Central Michigan University | Flame retardants from renewable resources |
| JP6820847B2 (ja) * | 2014-11-19 | 2021-01-27 | ニコックス エス.エー. | プロスタグランジンと一酸化窒素供与体との組み合わせ |
| 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 |
| WO2020030489A1 (en) * | 2018-08-06 | 2020-02-13 | Nicox S.A. | Nitric oxide releasing phosphodiesterase type 5 inhibitor |
| 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 CA CA2706082A patent/CA2706082C/en active Active
- 2009-01-15 EP EP09708682A patent/EP2238143B1/en not_active Not-in-force
- 2009-01-15 JP JP2010545422A patent/JP5441928B2/ja not_active Expired - Fee Related
- 2009-01-15 US US12/744,168 patent/US8003811B2/en active Active
- 2009-01-15 WO PCT/EP2009/050416 patent/WO2009098113A1/en not_active Ceased
- 2009-01-15 ES ES09708682T patent/ES2393049T3/es active Active
Also Published As
| Publication number | Publication date |
|---|---|
| WO2009098113A1 (en) | 2009-08-13 |
| ES2393049T3 (es) | 2012-12-18 |
| CA2706082C (en) | 2017-10-03 |
| US8003811B2 (en) | 2011-08-23 |
| CA2706082A1 (en) | 2009-08-13 |
| JP2011511022A (ja) | 2011-04-07 |
| EP2238143A1 (en) | 2010-10-13 |
| EP2238143B1 (en) | 2012-08-15 |
| US20100249189A1 (en) | 2010-09-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5441928B2 (ja) | 一酸化窒素供与化合物 | |
| CN113226327B (zh) | 可用于治疗流感病毒感染的化合物 | |
| ES2643132T3 (es) | Derivado de imidazol cicloalquilo sustituido | |
| ES2974494T3 (es) | Compuestos tricíclicos fusionados de piridazinona útiles para tratar las infecciones por ortomixovirus | |
| JP5265518B2 (ja) | アルテミシニン誘導体の二量体、この調製およびこの治療上の使用 | |
| ES2901401T3 (es) | Compuesto de dihidropirimidina y método de preparación y uso del mismo | |
| AU2021353722B2 (en) | Benzamide compound and use thereof | |
| TW202311260A (zh) | 含有亞磺醯亞胺基的atr抑制劑化合物 | |
| WO2015178265A1 (ja) | 新規なグルタミン酸誘導体およびその用途 | |
| WO2022090724A1 (en) | Novel compounds | |
| JP2023538638A (ja) | ピラゾールボロン酸化合物、それを含有する医薬組成物、及びそれらの使用 | |
| JP4923067B2 (ja) | カンプトテシン誘導体及びその応用 | |
| EP3759113B1 (en) | 10-(di(phenyl)methyl)-4-hydroxy-8,9,9a,10-tetrahydro-7h-pyrrolo[1',2':4,5]pyrazino[1,2-b]pyridazine-3,5-dione derivatives and related compounds as inhibitors of the orthomyxovirus replication for treating influenza | |
| EP4186900A1 (en) | Codrug that disintegrates in intestine, preparation therefor, and use thereof | |
| JPWO2001027115A1 (ja) | 五環性タキサン化合物 | |
| JP6912100B2 (ja) | 抗ウイルス活性等の生理活性を有するヌクレオシド誘導体 | |
| JP5994059B2 (ja) | 抗マラリア活性を有するアザアルテミシニン誘導体及びその製造方法 | |
| EP4289481B1 (en) | Method of synthesizing (3s,3ar,5r,7as,8s)- hexahydro-4h-3,5-methanofuro[2,3-b]pyran-8-ol | |
| US11407761B2 (en) | Derivative of β-apopicropodophyllin and method of preparing thereof | |
| HK40119293A (en) | Fused tricyclic pyridazinone compounds and prodrugs thereof useful to treat orthomyxovirus infections | |
| AU2022215029A1 (en) | Heteroaromatic phosphonium salts and their use treating cancer | |
| CN114621243A (zh) | 一种磺酰胺类衍生物及其用途 | |
| AU2021357608A9 (en) | Tetrahydrobenzofurodiazepinone compounds and pharmaceutical applications thereof | |
| WO2014169976A1 (en) | Quinone based nitric oxide donating compounds | |
| HK40050168B (en) | Compounds useful to treat influenza virus infections |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120111 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20120111 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130820 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20131105 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20131203 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20131217 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 Ref document number: 5441928 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
| S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |