JP2009530303A5 - - Google Patents
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- JP2009530303A5 JP2009530303A5 JP2009500519A JP2009500519A JP2009530303A5 JP 2009530303 A5 JP2009530303 A5 JP 2009530303A5 JP 2009500519 A JP2009500519 A JP 2009500519A JP 2009500519 A JP2009500519 A JP 2009500519A JP 2009530303 A5 JP2009530303 A5 JP 2009530303A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- substituted
- nitroxyl
- compound
- compounds
- 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.)
- Granted
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- 150000001875 compounds Chemical class 0.000 description 221
- ODUCDPQEXGNKDN-UHFFFAOYSA-N nitroxyl Chemical compound O=N ODUCDPQEXGNKDN-UHFFFAOYSA-N 0.000 description 139
- 125000000217 alkyl group Chemical group 0.000 description 132
- 238000000034 method Methods 0.000 description 73
- -1 aromatic N-hydroxylsulfonamide derivatives Chemical class 0.000 description 70
- 206010019280 Heart failures Diseases 0.000 description 63
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 60
- 125000003118 aryl group Chemical group 0.000 description 55
- 208000028867 ischemia Diseases 0.000 description 55
- 125000005843 halogen group Chemical group 0.000 description 54
- 201000010099 disease Diseases 0.000 description 44
- 239000000203 mixture Substances 0.000 description 43
- 125000000623 heterocyclic group Chemical group 0.000 description 38
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 38
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 38
- 230000005856 abnormality Effects 0.000 description 36
- 125000001072 heteroaryl group Chemical group 0.000 description 35
- 206010007559 Cardiac failure congestive Diseases 0.000 description 34
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 238000011282 treatment Methods 0.000 description 31
- 125000000753 cycloalkyl group Chemical group 0.000 description 30
- 210000002216 heart Anatomy 0.000 description 30
- 125000003342 alkenyl group Chemical group 0.000 description 27
- 229910052760 oxygen Inorganic materials 0.000 description 27
- 230000004962 physiological condition Effects 0.000 description 26
- 206010063837 Reperfusion injury Diseases 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
- 125000004663 dialkyl amino group Chemical group 0.000 description 23
- MWUXSHHQAYIFBG-UHFFFAOYSA-N nitrogen oxide Inorganic materials O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 23
- 150000003839 salts Chemical class 0.000 description 23
- 238000002560 therapeutic procedure Methods 0.000 description 23
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- 230000010410 reperfusion Effects 0.000 description 22
- 239000000243 solution Substances 0.000 description 22
- 210000001519 tissue Anatomy 0.000 description 22
- 125000003545 alkoxy group Chemical group 0.000 description 21
- 125000004093 cyano group Chemical group *C#N 0.000 description 21
- 230000000302 ischemic effect Effects 0.000 description 21
- 229910052717 sulfur Inorganic materials 0.000 description 20
- 229910052801 chlorine Inorganic materials 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- ZZRODMXZJNLQGD-UHFFFAOYSA-N ONS(=O)=O Chemical compound ONS(=O)=O ZZRODMXZJNLQGD-UHFFFAOYSA-N 0.000 description 18
- 239000003795 chemical substances by application Substances 0.000 description 18
- 210000000056 organ Anatomy 0.000 description 18
- 125000001424 substituent group Chemical group 0.000 description 18
- 125000000547 substituted alkyl group Chemical group 0.000 description 18
- 229910004013 NO 2 Inorganic materials 0.000 description 17
- 229910005965 SO 2 Inorganic materials 0.000 description 17
- 125000000304 alkynyl group Chemical group 0.000 description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
- 125000004414 alkyl thio group Chemical group 0.000 description 16
- 125000004104 aryloxy group Chemical group 0.000 description 16
- 239000002876 beta blocker Substances 0.000 description 16
- 208000035475 disorder Diseases 0.000 description 16
- 230000000694 effects Effects 0.000 description 16
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 15
- 125000004432 carbon atom Chemical group C* 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 15
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 14
- 125000003710 aryl alkyl group Chemical group 0.000 description 14
- 125000005163 aryl sulfanyl group Chemical group 0.000 description 14
- 125000005135 aryl sulfinyl group Chemical group 0.000 description 14
- 239000004041 inotropic agent Substances 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 229910052794 bromium Inorganic materials 0.000 description 13
- 125000000000 cycloalkoxy group Chemical group 0.000 description 13
- 125000005171 cycloalkylsulfanyl group Chemical group 0.000 description 13
- 239000003814 drug Substances 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- 208000024172 Cardiovascular disease Diseases 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 12
- 125000006575 electron-withdrawing group Chemical group 0.000 description 12
- 125000002252 acyl group Chemical group 0.000 description 11
- 210000004369 blood Anatomy 0.000 description 11
- 239000008280 blood Substances 0.000 description 11
- 229910052720 vanadium Inorganic materials 0.000 description 11
- 230000002861 ventricular Effects 0.000 description 11
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 10
- 241000700159 Rattus Species 0.000 description 10
- 229910052731 fluorine Inorganic materials 0.000 description 10
- 208000010125 myocardial infarction Diseases 0.000 description 10
- 230000010412 perfusion Effects 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 208000024891 symptom Diseases 0.000 description 10
- GQPLMRYTRLFLPF-UHFFFAOYSA-N Nitrous Oxide Chemical compound [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 125000004122 cyclic group Chemical group 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- 125000003107 substituted aryl group Chemical group 0.000 description 9
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 9
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 9
- 206010007556 Cardiac failure acute Diseases 0.000 description 8
- JRWZLRBJNMZMFE-UHFFFAOYSA-N Dobutamine Chemical compound C=1C=C(O)C(O)=CC=1CCNC(C)CCC1=CC=C(O)C=C1 JRWZLRBJNMZMFE-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 230000001154 acute effect Effects 0.000 description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 8
- 229910052799 carbon Inorganic materials 0.000 description 8
- 230000006378 damage Effects 0.000 description 8
- 238000000354 decomposition reaction Methods 0.000 description 8
- 229960001089 dobutamine Drugs 0.000 description 8
- 229910052740 iodine Inorganic materials 0.000 description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 8
- 239000001301 oxygen Substances 0.000 description 8
- 125000005017 substituted alkenyl group Chemical group 0.000 description 8
- 125000004426 substituted alkynyl group Chemical group 0.000 description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 125000004475 heteroaralkyl group Chemical group 0.000 description 7
- 229910052739 hydrogen Inorganic materials 0.000 description 7
- 230000004048 modification Effects 0.000 description 7
- 238000012986 modification Methods 0.000 description 7
- 230000002107 myocardial effect Effects 0.000 description 7
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 238000004809 thin layer chromatography Methods 0.000 description 7
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 6
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 6
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 6
- 208000004652 Cardiovascular Abnormalities Diseases 0.000 description 6
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 239000007900 aqueous suspension Substances 0.000 description 6
- 229910052791 calcium Inorganic materials 0.000 description 6
- 239000011575 calcium Substances 0.000 description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
- 208000029078 coronary artery disease Diseases 0.000 description 6
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 238000010874 in vitro model Methods 0.000 description 6
- 208000031225 myocardial ischemia Diseases 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 6
- 229940124597 therapeutic agent Drugs 0.000 description 6
- 229930192474 thiophene Natural products 0.000 description 6
- 239000003039 volatile agent Substances 0.000 description 6
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 5
- 208000003037 Diastolic Heart Failure Diseases 0.000 description 5
- 206010020772 Hypertension Diseases 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 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
- 239000000006 Nitroglycerin Substances 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 230000009286 beneficial effect Effects 0.000 description 5
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 5
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 5
- 230000000747 cardiac effect Effects 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 125000000524 functional group Chemical group 0.000 description 5
- 229960003711 glyceryl trinitrate Drugs 0.000 description 5
- 229910052736 halogen Inorganic materials 0.000 description 5
- 150000002367 halogens Chemical class 0.000 description 5
- 208000018578 heart valve disease Diseases 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 230000000297 inotrophic effect Effects 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- 210000003734 kidney Anatomy 0.000 description 5
- 208000037891 myocardial injury Diseases 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 125000004043 oxo group Chemical group O=* 0.000 description 5
- 125000004430 oxygen atom Chemical group O* 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- 238000001356 surgical procedure Methods 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- BASKBTQCHRZHSH-UHFFFAOYSA-N 2-chloro-n-hydroxybenzenesulfonamide Chemical compound ONS(=O)(=O)C1=CC=CC=C1Cl BASKBTQCHRZHSH-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 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
- 208000000059 Dyspnea Diseases 0.000 description 4
- 206010013975 Dyspnoeas Diseases 0.000 description 4
- 238000004435 EPR spectroscopy Methods 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 206010061216 Infarction Diseases 0.000 description 4
- RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 206010030113 Oedema Diseases 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 4
- BRMDATNYMUMZLN-UHFFFAOYSA-N Piloty's Acid Chemical compound ONS(=O)(=O)C1=CC=CC=C1 BRMDATNYMUMZLN-UHFFFAOYSA-N 0.000 description 4
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 208000027418 Wounds and injury Diseases 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 239000000808 adrenergic beta-agonist Substances 0.000 description 4
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- YFHXZQPUBCBNIP-UHFFFAOYSA-N fura-2 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=3OC(=CC=3C=2)C=2OC(=CN=2)C(O)=O)N(CC(O)=O)CC(O)=O)=C1 YFHXZQPUBCBNIP-UHFFFAOYSA-N 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 208000019622 heart disease Diseases 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
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- 208000014674 injury Diseases 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 210000003205 muscle Anatomy 0.000 description 4
- UHLUYTLUWPLQIV-UHFFFAOYSA-N n-hydroxy-2-(trifluoromethyl)benzenesulfonamide Chemical compound ONS(=O)(=O)C1=CC=CC=C1C(F)(F)F UHLUYTLUWPLQIV-UHFFFAOYSA-N 0.000 description 4
- 239000002840 nitric oxide donor Substances 0.000 description 4
- 239000001272 nitrous oxide Substances 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 4
- 230000037081 physical activity Effects 0.000 description 4
- 230000009090 positive inotropic effect Effects 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 125000006413 ring segment Chemical group 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000013268 sustained release Methods 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 3
- JTMRAKAVHPQVLR-UHFFFAOYSA-N 2-bromo-n-hydroxybenzenesulfonamide Chemical compound ONS(=O)(=O)C1=CC=CC=C1Br JTMRAKAVHPQVLR-UHFFFAOYSA-N 0.000 description 3
- HOOBKHGRGVPCEC-UHFFFAOYSA-N 2-bromo-n-phenylmethoxybenzenesulfonamide Chemical compound BrC1=CC=CC=C1S(=O)(=O)NOCC1=CC=CC=C1 HOOBKHGRGVPCEC-UHFFFAOYSA-N 0.000 description 3
- QVWABNGSRMHSSC-UHFFFAOYSA-N 2-fluoro-n-hydroxybenzenesulfonamide Chemical compound ONS(=O)(=O)C1=CC=CC=C1F QVWABNGSRMHSSC-UHFFFAOYSA-N 0.000 description 3
- PUEBDJPCIGWIIP-UHFFFAOYSA-N 2-phenyl-n-phenylmethoxybenzenesulfonamide Chemical compound C=1C=CC=C(C=2C=CC=CC=2)C=1S(=O)(=O)NOCC1=CC=CC=C1 PUEBDJPCIGWIIP-UHFFFAOYSA-N 0.000 description 3
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- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
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- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
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- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
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- 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 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 206010037368 Pulmonary congestion Diseases 0.000 description 3
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 208000008253 Systolic Heart Failure Diseases 0.000 description 3
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 125000004442 acylamino group Chemical group 0.000 description 3
- 239000000464 adrenergic agent Substances 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 229940125388 beta agonist Drugs 0.000 description 3
- 229940097320 beta blocking agent Drugs 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 description 3
- 125000004181 carboxyalkyl group Chemical group 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 238000004587 chromatography analysis Methods 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
- 238000013270 controlled release Methods 0.000 description 3
- 210000004351 coronary vessel Anatomy 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
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