NO315556B1 - Kromaner, deres fremstilling og anvendelse samt medikamenter inneholdende forbindelsene - Google Patents
Kromaner, deres fremstilling og anvendelse samt medikamenter inneholdende forbindelsene Download PDFInfo
- Publication number
- NO315556B1 NO315556B1 NO19972211A NO972211A NO315556B1 NO 315556 B1 NO315556 B1 NO 315556B1 NO 19972211 A NO19972211 A NO 19972211A NO 972211 A NO972211 A NO 972211A NO 315556 B1 NO315556 B1 NO 315556B1
- Authority
- NO
- Norway
- Prior art keywords
- amino
- dimethylchroman
- formula
- methyl
- ethylsulfonyl
- Prior art date
Links
- 239000003814 drug Substances 0.000 title claims abstract description 29
- 229940079593 drug Drugs 0.000 title claims abstract description 24
- 150000001875 compounds Chemical class 0.000 title claims description 88
- 238000002360 preparation method Methods 0.000 title claims description 19
- 238000002483 medication Methods 0.000 title 1
- 206010003119 arrhythmia Diseases 0.000 claims abstract description 13
- 230000006793 arrhythmia Effects 0.000 claims abstract description 11
- 150000001843 chromanes Chemical class 0.000 claims abstract description 9
- 238000004519 manufacturing process Methods 0.000 claims abstract description 9
- 230000000903 blocking effect Effects 0.000 claims abstract description 8
- 230000002265 prevention Effects 0.000 claims abstract description 8
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 claims abstract description 7
- 210000002784 stomach Anatomy 0.000 claims abstract description 7
- 208000003663 ventricular fibrillation Diseases 0.000 claims abstract description 6
- 206010049418 Sudden Cardiac Death Diseases 0.000 claims abstract description 5
- 206010042600 Supraventricular arrhythmias Diseases 0.000 claims abstract description 5
- 208000025865 Ulcer Diseases 0.000 claims abstract description 5
- 206010047281 Ventricular arrhythmia Diseases 0.000 claims abstract description 5
- 210000001198 duodenum Anatomy 0.000 claims abstract description 5
- 230000027119 gastric acid secretion Effects 0.000 claims abstract description 5
- 208000021302 gastroesophageal reflux disease Diseases 0.000 claims abstract description 5
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 5
- 230000000968 intestinal effect Effects 0.000 claims abstract description 5
- 231100000397 ulcer Toxicity 0.000 claims abstract description 5
- 230000002861 ventricular Effects 0.000 claims abstract description 5
- 206010012735 Diarrhoea Diseases 0.000 claims abstract description 4
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 4
- 239000001257 hydrogen Substances 0.000 claims description 57
- 229910052739 hydrogen Inorganic materials 0.000 claims description 57
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 35
- 238000000034 method Methods 0.000 claims description 34
- -1 N-morpholino Chemical group 0.000 claims description 30
- 239000000460 chlorine Substances 0.000 claims description 24
- 229910052801 chlorine Inorganic materials 0.000 claims description 23
- 150000002431 hydrogen Chemical class 0.000 claims description 22
- 229910052794 bromium Inorganic materials 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 229910052731 fluorine Inorganic materials 0.000 claims description 18
- 229910052740 iodine Inorganic materials 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 13
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
- 229940124530 sulfonamide Drugs 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 150000003456 sulfonamides Chemical class 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 230000005764 inhibitory process Effects 0.000 claims description 8
- 238000005804 alkylation reaction Methods 0.000 claims description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 5
- 239000002168 alkylating agent Substances 0.000 claims description 5
- 229940100198 alkylating agent Drugs 0.000 claims description 5
- 239000011734 sodium Substances 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 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 claims description 4
- 230000029936 alkylation Effects 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 125000005936 piperidyl group Chemical group 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 3
- 125000002252 acyl group Chemical group 0.000 claims description 3
- 238000007336 electrophilic substitution reaction Methods 0.000 claims description 3
- 229910052700 potassium Inorganic materials 0.000 claims description 3
- 239000011591 potassium Substances 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 2
- 229910004013 NO 2 Inorganic materials 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 229910052744 lithium Inorganic materials 0.000 claims description 2
- 229910052751 metal Inorganic materials 0.000 claims description 2
- 239000002184 metal Substances 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 150000003458 sulfonic acid derivatives Chemical class 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- 210000004211 gastric acid Anatomy 0.000 claims 1
- 208000000689 peptic esophagitis Diseases 0.000 abstract description 2
- 208000014221 sudden cardiac arrest Diseases 0.000 abstract 1
- 238000002844 melting Methods 0.000 description 156
- 230000008018 melting Effects 0.000 description 156
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 72
- 239000000047 product Substances 0.000 description 61
- 239000000126 substance Substances 0.000 description 61
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 55
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 53
- 239000002904 solvent Substances 0.000 description 52
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
- 239000013078 crystal Substances 0.000 description 40
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 39
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 39
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 38
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- 108091006146 Channels Proteins 0.000 description 33
- 239000003921 oil Substances 0.000 description 31
- 235000019198 oils Nutrition 0.000 description 31
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 30
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
- 239000000243 solution Substances 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- 229910000104 sodium hydride Inorganic materials 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 23
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 21
- 239000000725 suspension Substances 0.000 description 21
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 20
- 239000000203 mixture Substances 0.000 description 20
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 19
- FRYHCSODNHYDPU-UHFFFAOYSA-N ethanesulfonyl chloride Chemical compound CCS(Cl)(=O)=O FRYHCSODNHYDPU-UHFFFAOYSA-N 0.000 description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 16
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 15
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- 239000000741 silica gel Substances 0.000 description 15
- 229910002027 silica gel Inorganic materials 0.000 description 15
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 14
- 239000012312 sodium hydride Substances 0.000 description 14
- 238000003756 stirring Methods 0.000 description 13
- 238000010626 work up procedure Methods 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 11
- 239000003480 eluent Substances 0.000 description 11
- LNDGACQEAYKNOI-UHFFFAOYSA-N 1,1,1-trifluoro-4-iodobutane Chemical compound FC(F)(F)CCCI LNDGACQEAYKNOI-UHFFFAOYSA-N 0.000 description 10
- UAXWPLCLDSMHRF-UHFFFAOYSA-N 2,2-dimethyl-6-hydroxychroman-4-one Natural products OC1=CC=C2OC(C)(C)CC(=O)C2=C1 UAXWPLCLDSMHRF-UHFFFAOYSA-N 0.000 description 10
- 230000009471 action Effects 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 150000001412 amines Chemical class 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 8
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 8
- 238000002425 crystallisation Methods 0.000 description 8
- 230000008025 crystallization Effects 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- 229910021529 ammonia Inorganic materials 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 239000012230 colorless oil Substances 0.000 description 7
- 238000004440 column chromatography Methods 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- ZCZUDOBLRMXOGV-UHFFFAOYSA-N 2,3-Dihydro-6-methoxy-2,2-dimethyl-4H-1-benzopyran-4-one Chemical compound O1C(C)(C)CC(=O)C2=CC(OC)=CC=C21 ZCZUDOBLRMXOGV-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 230000003288 anthiarrhythmic effect Effects 0.000 description 6
- KMGBZBJJOKUPIA-UHFFFAOYSA-N butyl iodide Chemical compound CCCCI KMGBZBJJOKUPIA-UHFFFAOYSA-N 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- OHBAWAXGKXWFAZ-UHFFFAOYSA-N 2,2-dimethyl-3,4-dihydrochromen-4-amine;hydrochloride Chemical compound Cl.C1=CC=C2OC(C)(C)CC(N)C2=C1 OHBAWAXGKXWFAZ-UHFFFAOYSA-N 0.000 description 5
- 229910000564 Raney nickel Inorganic materials 0.000 description 5
- 238000009825 accumulation Methods 0.000 description 5
- 239000013543 active substance Substances 0.000 description 5
- 239000003416 antiarrhythmic agent Substances 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 238000004140 cleaning Methods 0.000 description 5
- 210000001156 gastric mucosa Anatomy 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- 239000005457 ice water Substances 0.000 description 5
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 5
- IFUDNQFEYVTYQW-UHFFFAOYSA-N methyl 4-amino-2,2-dimethyl-3,4-dihydrochromene-6-carboxylate Chemical compound O1C(C)(C)CC(N)C2=CC(C(=O)OC)=CC=C21 IFUDNQFEYVTYQW-UHFFFAOYSA-N 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- AVQQQNCBBIEMEU-UHFFFAOYSA-N 1,1,3,3-tetramethylurea Chemical compound CN(C)C(=O)N(C)C AVQQQNCBBIEMEU-UHFFFAOYSA-N 0.000 description 4
- KOFFXZYMDLWRHX-UHFFFAOYSA-N 1-(5-fluoro-2-hydroxyphenyl)ethanone Chemical compound CC(=O)C1=CC(F)=CC=C1O KOFFXZYMDLWRHX-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- 239000007868 Raney catalyst Substances 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 150000002923 oximes Chemical class 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- PBKONEOXTCPAFI-UHFFFAOYSA-N 1,2,4-trichlorobenzene Chemical compound ClC1=CC=C(Cl)C(Cl)=C1 PBKONEOXTCPAFI-UHFFFAOYSA-N 0.000 description 3
- ANOOTOPTCJRUPK-UHFFFAOYSA-N 1-iodohexane Chemical compound CCCCCCI ANOOTOPTCJRUPK-UHFFFAOYSA-N 0.000 description 3
- NBUWNTIATBQVDR-UHFFFAOYSA-N 2,2-dimethyl-3,4-dihydrochromene-6-carbonitrile Chemical compound N#CC1=CC=C2OC(C)(C)CCC2=C1 NBUWNTIATBQVDR-UHFFFAOYSA-N 0.000 description 3
- FPBXWXGOFQSROI-UHFFFAOYSA-N 3-acetyl-4-hydroxybenzoic acid Chemical compound CC(=O)C1=CC(C(O)=O)=CC=C1O FPBXWXGOFQSROI-UHFFFAOYSA-N 0.000 description 3
- PLEFHPWZHDJYFJ-UHFFFAOYSA-N 4-amino-2,2-dimethyl-3,4-dihydrochromene-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2OC(C)(C)CC(N)C2=C1 PLEFHPWZHDJYFJ-UHFFFAOYSA-N 0.000 description 3
- 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
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 3
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000003995 emulsifying agent Substances 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 235000001727 glucose Nutrition 0.000 description 3
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 239000000155 melt Substances 0.000 description 3
- JFCHSQDLLFJHOA-UHFFFAOYSA-N n,n-dimethylsulfamoyl chloride Chemical compound CN(C)S(Cl)(=O)=O JFCHSQDLLFJHOA-UHFFFAOYSA-N 0.000 description 3
- APFSTNQKPGEBHQ-UHFFFAOYSA-N n-(6-fluoro-3,4-dihydro-2h-chromen-4-yl)ethanesulfonamide Chemical compound C1=C(F)C=C2C(NS(=O)(=O)CC)CCOC2=C1 APFSTNQKPGEBHQ-UHFFFAOYSA-N 0.000 description 3
- UNXIXBDISARUMK-UHFFFAOYSA-N n-(7-chloro-6-fluoro-2,2-dimethyl-3,4-dihydrochromen-4-yl)ethanesulfonamide Chemical compound ClC1=C(F)C=C2C(NS(=O)(=O)CC)CC(C)(C)OC2=C1 UNXIXBDISARUMK-UHFFFAOYSA-N 0.000 description 3
- NIYGLRKUBPNXQS-FYYLOGMGSA-N n-[(4r)-1'-[(2r)-6-cyano-1,2,3,4-tetrahydronaphthalen-2-yl]-4-hydroxyspiro[3,4-dihydrochromene-2,4'-piperidine]-6-yl]methanesulfonamide Chemical compound C1CC2=CC(C#N)=CC=C2C[C@@H]1N(CC1)CCC11OC2=CC=C(NS(=O)(=O)C)C=C2[C@H](O)C1 NIYGLRKUBPNXQS-FYYLOGMGSA-N 0.000 description 3
- 210000000287 oocyte Anatomy 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 210000002460 smooth muscle Anatomy 0.000 description 3
- SCDFAHSIYYBVTF-UHFFFAOYSA-N (3,4-difluorophenyl) acetate Chemical compound CC(=O)OC1=CC=C(F)C(F)=C1 SCDFAHSIYYBVTF-UHFFFAOYSA-N 0.000 description 2
- IPSIPXOXHRSGTM-UHFFFAOYSA-N (3-chloro-4-fluorophenyl) acetate Chemical compound CC(=O)OC1=CC=C(F)C(Cl)=C1 IPSIPXOXHRSGTM-UHFFFAOYSA-N 0.000 description 2
- HFWBXYDXTXEIIQ-UHFFFAOYSA-N (4-amino-2,2-dimethyl-3,4-dihydrochromen-6-yl) methanesulfonate;hydrochloride Chemical compound Cl.CS(=O)(=O)OC1=CC=C2OC(C)(C)CC(N)C2=C1 HFWBXYDXTXEIIQ-UHFFFAOYSA-N 0.000 description 2
- ZNOREXRHKZXVPC-UHFFFAOYSA-N (4-fluorophenyl) acetate Chemical compound CC(=O)OC1=CC=C(F)C=C1 ZNOREXRHKZXVPC-UHFFFAOYSA-N 0.000 description 2
- MISFQCBPASYYGV-UHFFFAOYSA-N (4-phenylphenyl) acetate Chemical group C1=CC(OC(=O)C)=CC=C1C1=CC=CC=C1 MISFQCBPASYYGV-UHFFFAOYSA-N 0.000 description 2
- MCDJUVXLLXTCFP-UHFFFAOYSA-N 1-(3,5-difluoro-2-hydroxyphenyl)ethanone Chemical compound CC(=O)C1=CC(F)=CC(F)=C1O MCDJUVXLLXTCFP-UHFFFAOYSA-N 0.000 description 2
- GSTOHKXQBZZTPF-UHFFFAOYSA-N 1-(5-ethyl-2-hydroxyphenyl)ethanone Chemical compound CCC1=CC=C(O)C(C(C)=O)=C1 GSTOHKXQBZZTPF-UHFFFAOYSA-N 0.000 description 2
- SMKJTFWQUPHWOC-UHFFFAOYSA-N 1-[5-(4-bromophenyl)-2-hydroxyphenyl]ethanone Chemical group C1=C(O)C(C(=O)C)=CC(C=2C=CC(Br)=CC=2)=C1 SMKJTFWQUPHWOC-UHFFFAOYSA-N 0.000 description 2
- QYFREVFIVRIKQH-UHFFFAOYSA-N 2,2,6,7-tetramethyl-3,4-dihydrochromen-4-amine Chemical compound O1C(C)(C)CC(N)C2=C1C=C(C)C(C)=C2 QYFREVFIVRIKQH-UHFFFAOYSA-N 0.000 description 2
- MWCLIHHFUUYVDF-UHFFFAOYSA-N 2,2,6-trimethyl-3h-chromen-4-one Chemical compound O1C(C)(C)CC(=O)C2=CC(C)=CC=C21 MWCLIHHFUUYVDF-UHFFFAOYSA-N 0.000 description 2
- PTOMGSWLGSRLCK-UHFFFAOYSA-N 2,2-dimethyl-4-oxo-3h-chromene-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2OC(C)(C)CC(=O)C2=C1 PTOMGSWLGSRLCK-UHFFFAOYSA-N 0.000 description 2
- WXIOJWVNDKRWJF-UHFFFAOYSA-N 2,2-dimethyl-6-(4,4,4-trifluorobutoxy)-3,4-dihydrochromen-4-amine Chemical compound FC(F)(F)CCCOC1=CC=C2OC(C)(C)CC(N)C2=C1 WXIOJWVNDKRWJF-UHFFFAOYSA-N 0.000 description 2
- UKCXKMVTLZLMAX-UHFFFAOYSA-N 2,2-dimethyl-6-phenyl-3,4-dihydrochromen-4-amine;hydrochloride Chemical compound Cl.C=1C=C2OC(C)(C)CC(N)C2=CC=1C1=CC=CC=C1 UKCXKMVTLZLMAX-UHFFFAOYSA-N 0.000 description 2
- WJEHYLUPSZZILR-UHFFFAOYSA-N 2,6-dimethyl-3,4-dihydro-2h-chromene Chemical compound CC1=CC=C2OC(C)CCC2=C1 WJEHYLUPSZZILR-UHFFFAOYSA-N 0.000 description 2
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-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
- HBLDKCGIBIGVPC-UHFFFAOYSA-N 3,4-dihydro-2h-chromen-3-ol Chemical class C1=CC=C2CC(O)COC2=C1 HBLDKCGIBIGVPC-UHFFFAOYSA-N 0.000 description 2
- IIBHQTXJTUSHBK-UHFFFAOYSA-N 4-bromo-2,2-dimethyl-3,4-dihydrochromene-6-carbonitrile Chemical compound N#CC1=CC=C2OC(C)(C)CC(Br)C2=C1 IIBHQTXJTUSHBK-UHFFFAOYSA-N 0.000 description 2
- HXDOZKJGKXYMEW-UHFFFAOYSA-N 4-ethylphenol Chemical compound CCC1=CC=C(O)C=C1 HXDOZKJGKXYMEW-UHFFFAOYSA-N 0.000 description 2
- VSNPRKDVSQYMPC-UHFFFAOYSA-N 4-hydroxyimino-2,2-dimethyl-3H-chromene-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2OC(C)(C)CC(=NO)C2=C1 VSNPRKDVSQYMPC-UHFFFAOYSA-N 0.000 description 2
- CYYQCHBLHSIWSN-UHFFFAOYSA-N 6,7-dichloro-2,2-dimethyl-3,4-dihydrochromen-4-amine;hydrochloride Chemical compound Cl.ClC1=C(Cl)C=C2OC(C)(C)CC(N)C2=C1 CYYQCHBLHSIWSN-UHFFFAOYSA-N 0.000 description 2
- LTWSLRBUUBTDTG-UHFFFAOYSA-N 6,7-dichloro-2,2-dimethyl-3h-chromen-4-one Chemical compound ClC1=C(Cl)C=C2OC(C)(C)CC(=O)C2=C1 LTWSLRBUUBTDTG-UHFFFAOYSA-N 0.000 description 2
- OMWVNQFGCGNZHE-UHFFFAOYSA-N 6,7-dimethoxy-2,2-dimethyl-3h-chromen-4-one Chemical compound O1C(C)(C)CC(=O)C2=C1C=C(OC)C(OC)=C2 OMWVNQFGCGNZHE-UHFFFAOYSA-N 0.000 description 2
- CQHBZGOGXXIFBT-UHFFFAOYSA-N 6,8-difluoro-2,2-dimethyl-3,4-dihydrochromen-4-amine;hydrochloride Chemical compound Cl.FC1=CC(F)=C2OC(C)(C)CC(N)C2=C1 CQHBZGOGXXIFBT-UHFFFAOYSA-N 0.000 description 2
- NHXQSAXNVCFRKP-UHFFFAOYSA-N 6,8-difluoro-2,2-dimethyl-3h-chromen-4-one Chemical compound FC1=CC(F)=C2OC(C)(C)CC(=O)C2=C1 NHXQSAXNVCFRKP-UHFFFAOYSA-N 0.000 description 2
- ZIAYCRDHSNHXOG-UHFFFAOYSA-N 6-(4-bromophenyl)-2,2-dimethyl-3h-chromen-4-one Chemical compound C=1C=C2OC(C)(C)CC(=O)C2=CC=1C1=CC=C(Br)C=C1 ZIAYCRDHSNHXOG-UHFFFAOYSA-N 0.000 description 2
- ICCUWDQOENJRLO-UHFFFAOYSA-N 6-ethyl-2,2-dimethyl-3,4-dihydrochromen-4-amine;hydrochloride Chemical compound Cl.O1C(C)(C)CC(N)C2=CC(CC)=CC=C21 ICCUWDQOENJRLO-UHFFFAOYSA-N 0.000 description 2
- WSLHNSBKXLMKOU-UHFFFAOYSA-N 6-ethyl-2,2-dimethyl-3h-chromen-4-one Chemical compound O1C(C)(C)CC(=O)C2=CC(CC)=CC=C21 WSLHNSBKXLMKOU-UHFFFAOYSA-N 0.000 description 2
- MPJMDEXLUJRBBJ-UHFFFAOYSA-N 6-fluoro-2,2-dimethyl-3h-chromen-4-one Chemical compound FC1=CC=C2OC(C)(C)CC(=O)C2=C1 MPJMDEXLUJRBBJ-UHFFFAOYSA-N 0.000 description 2
- MZLPOLIBBWRNPP-UHFFFAOYSA-N 6-fluoro-2,2-dimethyl-7-pyrrolidin-1-yl-3h-chromen-4-one Chemical compound C1=C2OC(C)(C)CC(=O)C2=CC(F)=C1N1CCCC1 MZLPOLIBBWRNPP-UHFFFAOYSA-N 0.000 description 2
- QTUMYGSIHORDJL-UHFFFAOYSA-N 7-chloro-6-fluoro-2,2-dimethyl-3,4-dihydrochromen-4-amine;hydrochloride Chemical compound Cl.FC1=C(Cl)C=C2OC(C)(C)CC(N)C2=C1 QTUMYGSIHORDJL-UHFFFAOYSA-N 0.000 description 2
- ILVYMPMYKKRSPO-UHFFFAOYSA-N 7-methoxy-2,2-dimethyl-3,4-dihydrochromen-4-amine Chemical compound NC1CC(C)(C)OC2=CC(OC)=CC=C21 ILVYMPMYKKRSPO-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
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- WBBBEAQRMGIIIW-UHFFFAOYSA-N C1=C2OC(C)(C)CC(=NO)C2=CC(F)=C1N1CCCC1 Chemical compound C1=C2OC(C)(C)CC(=NO)C2=CC(F)=C1N1CCCC1 WBBBEAQRMGIIIW-UHFFFAOYSA-N 0.000 description 2
- JVPBOLPDUWAYAL-UHFFFAOYSA-N C=1C=C2OC(C)(C)CC(=NO)C2=CC=1C1=CC=C(Br)C=C1 Chemical compound C=1C=C2OC(C)(C)CC(=NO)C2=CC=1C1=CC=C(Br)C=C1 JVPBOLPDUWAYAL-UHFFFAOYSA-N 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- NQYDZGWUODJYNG-UHFFFAOYSA-N FC(F)(F)CCCOC1=CC=C2OC(C)(C)CC(=NO)C2=C1 Chemical compound FC(F)(F)CCCOC1=CC=C2OC(C)(C)CC(=NO)C2=C1 NQYDZGWUODJYNG-UHFFFAOYSA-N 0.000 description 2
- CTLUYYHOGYSBSH-UHFFFAOYSA-N FC1=C(Cl)C=C2OC(C)(C)CC(=NO)C2=C1 Chemical compound FC1=C(Cl)C=C2OC(C)(C)CC(=NO)C2=C1 CTLUYYHOGYSBSH-UHFFFAOYSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound 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 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- GDPBZFJOCVCFBX-UHFFFAOYSA-N N-(2,2-dimethyl-3H-chromen-4-ylidene)hydroxylamine Chemical compound C1=CC=C2OC(C)(C)CC(=NO)C2=C1 GDPBZFJOCVCFBX-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- FEWCTJHCXOHWNL-UHFFFAOYSA-N Roxatidine acetate hydrochloride Chemical compound Cl.CC(=O)OCC(=O)NCCCOC1=CC=CC(CN2CCCCC2)=C1 FEWCTJHCXOHWNL-UHFFFAOYSA-N 0.000 description 2
- 239000002262 Schiff base Substances 0.000 description 2
- 150000004753 Schiff bases Chemical class 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 241000269370 Xenopus <genus> Species 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 230000001800 adrenalinergic effect Effects 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- YXVFYQXJAXKLAK-UHFFFAOYSA-N biphenyl-4-ol Chemical group C1=CC(O)=CC=C1C1=CC=CC=C1 YXVFYQXJAXKLAK-UHFFFAOYSA-N 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 235000011148 calcium chloride Nutrition 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical compound [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 description 2
- 229960004484 carbachol Drugs 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 230000026030 halogenation Effects 0.000 description 2
- 238000005658 halogenation reaction Methods 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 150000007857 hydrazones Chemical class 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 239000003999 initiator Substances 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 210000004877 mucosa Anatomy 0.000 description 2
- OWGYOBHNMLWQDC-UHFFFAOYSA-N n-(2,2,6-trimethyl-3h-chromen-4-ylidene)hydroxylamine Chemical compound O1C(C)(C)CC(=NO)C2=CC(C)=CC=C21 OWGYOBHNMLWQDC-UHFFFAOYSA-N 0.000 description 2
- AMODJIKAKVHUFI-UHFFFAOYSA-N n-(2,2-dimethyl-6-phenyl-3h-chromen-4-ylidene)hydroxylamine Chemical compound C=1C=C2OC(C)(C)CC(=NO)C2=CC=1C1=CC=CC=C1 AMODJIKAKVHUFI-UHFFFAOYSA-N 0.000 description 2
- CQFRPHUTZHSMOP-UHFFFAOYSA-N n-(6,7-dichloro-2,2-dimethyl-3h-chromen-4-ylidene)hydroxylamine Chemical compound ClC1=C(Cl)C=C2OC(C)(C)CC(=NO)C2=C1 CQFRPHUTZHSMOP-UHFFFAOYSA-N 0.000 description 2
- YUBRIOSETGSKGV-UHFFFAOYSA-N n-(6-ethyl-2,2-dimethyl-3h-chromen-4-ylidene)hydroxylamine Chemical compound O1C(C)(C)CC(=NO)C2=CC(CC)=CC=C21 YUBRIOSETGSKGV-UHFFFAOYSA-N 0.000 description 2
- BZBXTOXIAXZPQZ-UHFFFAOYSA-N n-(6-fluoro-2,2-dimethyl-3h-chromen-4-ylidene)hydroxylamine Chemical compound FC1=CC=C2OC(C)(C)CC(=NO)C2=C1 BZBXTOXIAXZPQZ-UHFFFAOYSA-N 0.000 description 2
- OOCJVKPPHVLPIM-UHFFFAOYSA-N n-(6-fluoro-2,3-dihydrochromen-4-ylidene)hydroxylamine Chemical compound C1=C(F)C=C2C(=NO)CCOC2=C1 OOCJVKPPHVLPIM-UHFFFAOYSA-N 0.000 description 2
- PXSVMKRGPKFNRM-UHFFFAOYSA-N n-(6-methoxy-2,2-dimethyl-3h-chromen-4-ylidene)hydroxylamine Chemical compound O1C(C)(C)CC(=NO)C2=CC(OC)=CC=C21 PXSVMKRGPKFNRM-UHFFFAOYSA-N 0.000 description 2
- PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 2
- 229910052759 nickel Inorganic materials 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 230000001536 pro-arrhythmogenic effect Effects 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000000859 sublimation Methods 0.000 description 2
- 230000008022 sublimation Effects 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 230000001960 triggered effect Effects 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- XDUKPUDGTQCPFY-UHFFFAOYSA-N (2,5-dihydroxyphenyl) acetate Chemical compound CC(=O)OC1=CC(O)=CC=C1O XDUKPUDGTQCPFY-UHFFFAOYSA-N 0.000 description 1
- ANMYMLIUCWWISO-UHFFFAOYSA-N (4-ethylphenyl) acetate Chemical compound CCC1=CC=C(OC(C)=O)C=C1 ANMYMLIUCWWISO-UHFFFAOYSA-N 0.000 description 1
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- PHFFZLIQGNLRRH-BYEGLACWSA-N 1-[(e)-[5-(4-chlorophenyl)furan-2-yl]methylideneamino]-3-[3-[4-(2-hydroxyethyl)piperazin-1-yl]propyl]imidazolidine-2,4-dione;dihydrochloride Chemical compound Cl.Cl.C1CN(CCO)CCN1CCCN1C(=O)N(\N=C\C=2OC(=CC=2)C=2C=CC(Cl)=CC=2)CC1=O PHFFZLIQGNLRRH-BYEGLACWSA-N 0.000 description 1
- MREBEPTUUMTTIA-XYGWBWBKSA-N 1-[(z)-[5-(4-chlorophenyl)furan-2-yl]methylideneamino]-3-[4-(4-methylpiperazin-1-yl)butyl]imidazolidine-2,4-dione Chemical compound C1CN(C)CCN1CCCCN1C(=O)N(\N=C/C=2OC(=CC=2)C=2C=CC(Cl)=CC=2)CC1=O MREBEPTUUMTTIA-XYGWBWBKSA-N 0.000 description 1
- TYODDTFWIMEWAD-UHFFFAOYSA-N 1-ethoxy-3-iodopropane Chemical compound CCOCCCI TYODDTFWIMEWAD-UHFFFAOYSA-N 0.000 description 1
- BUZZUHJODKQYTF-UHFFFAOYSA-N 1-iodo-3-methylbutane Chemical compound CC(C)CCI BUZZUHJODKQYTF-UHFFFAOYSA-N 0.000 description 1
- BLXSFCHWMBESKV-UHFFFAOYSA-N 1-iodopentane Chemical compound CCCCCI BLXSFCHWMBESKV-UHFFFAOYSA-N 0.000 description 1
- LUBVCBITQHEVCJ-UHFFFAOYSA-N 1-trimethylsilylpyrrolidin-2-one Chemical compound C[Si](C)(C)N1CCCC1=O LUBVCBITQHEVCJ-UHFFFAOYSA-N 0.000 description 1
- AQAYMJHZXGZFBL-UHFFFAOYSA-N 2,2,6,7-tetramethyl-3h-chromen-4-one Chemical compound O1C(C)(C)CC(=O)C2=C1C=C(C)C(C)=C2 AQAYMJHZXGZFBL-UHFFFAOYSA-N 0.000 description 1
- CBXHPVYUFZUKPP-UHFFFAOYSA-N 2,2,6-trimethyl-3,4-dihydrochromen-4-amine;hydrochloride Chemical compound Cl.O1C(C)(C)CC(N)C2=CC(C)=CC=C21 CBXHPVYUFZUKPP-UHFFFAOYSA-N 0.000 description 1
- YKURFHOYVQJKSA-UHFFFAOYSA-N 2,2-dimethyl-3,4-dihydrochromen-3-amine Chemical compound C1=CC=C2CC(N)C(C)(C)OC2=C1 YKURFHOYVQJKSA-UHFFFAOYSA-N 0.000 description 1
- MITIYLBEZOKYLX-UHFFFAOYSA-N 2,2-dimethyl-3,4-dihydrochromene Chemical compound C1=CC=C2OC(C)(C)CCC2=C1 MITIYLBEZOKYLX-UHFFFAOYSA-N 0.000 description 1
- TWTOMQLOZLAJFJ-UHFFFAOYSA-N 2,2-dimethyl-3-oxo-4h-chromene-6-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2CC(=O)C(C)(C)OC2=C1 TWTOMQLOZLAJFJ-UHFFFAOYSA-N 0.000 description 1
- VLBUGUIIJYKNNT-UHFFFAOYSA-N 2,2-dimethyl-6-(4,4,4-trifluorobutoxy)-3h-chromen-4-one Chemical compound FC(F)(F)CCCOC1=CC=C2OC(C)(C)CC(=O)C2=C1 VLBUGUIIJYKNNT-UHFFFAOYSA-N 0.000 description 1
- QZBUNLDATRRBND-UHFFFAOYSA-N 2,2-dimethyl-6-phenyl-3h-chromen-4-one Chemical compound C=1C=C2OC(C)(C)CC(=O)C2=CC=1C1=CC=CC=C1 QZBUNLDATRRBND-UHFFFAOYSA-N 0.000 description 1
- HFFXLYHRNRKAPM-UHFFFAOYSA-N 2,4,5-trichloro-n-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C(=CC(Cl)=C(Cl)C=2)Cl)=N1 HFFXLYHRNRKAPM-UHFFFAOYSA-N 0.000 description 1
- NVWVWEWVLBKPSM-UHFFFAOYSA-N 2,4-difluorophenol Chemical compound OC1=CC=C(F)C=C1F NVWVWEWVLBKPSM-UHFFFAOYSA-N 0.000 description 1
- LQLJZSJKRYTKTP-UHFFFAOYSA-N 2-dimethylaminoethyl chloride hydrochloride Chemical compound Cl.CN(C)CCCl LQLJZSJKRYTKTP-UHFFFAOYSA-N 0.000 description 1
- CEJINNSYZFLSCS-UHFFFAOYSA-N 2-hydroxy-1-(2-methylphenyl)ethanone Chemical compound CC1=CC=CC=C1C(=O)CO CEJINNSYZFLSCS-UHFFFAOYSA-N 0.000 description 1
- WDNBURPWRNALGP-UHFFFAOYSA-N 3,4-Dichlorophenol Chemical compound OC1=CC=C(Cl)C(Cl)=C1 WDNBURPWRNALGP-UHFFFAOYSA-N 0.000 description 1
- BNPWVUJOPCGHIK-UHFFFAOYSA-N 3,4-difluorophenol Chemical compound OC1=CC=C(F)C(F)=C1 BNPWVUJOPCGHIK-UHFFFAOYSA-N 0.000 description 1
- ZQXLIXHVJVAPLW-UHFFFAOYSA-N 3-chloro-4-fluorophenol Chemical compound OC1=CC=C(F)C(Cl)=C1 ZQXLIXHVJVAPLW-UHFFFAOYSA-N 0.000 description 1
- WZIYCIBURCPKAR-UHFFFAOYSA-N 4-(chloromethyl)pyridine Chemical compound ClCC1=CC=NC=C1 WZIYCIBURCPKAR-UHFFFAOYSA-N 0.000 description 1
- JOXZTUJZGKRJGL-UHFFFAOYSA-N 4-(sulfonylamino)-3,4-dihydro-2h-chromene Chemical group C1=CC=C2C(N=S(=O)=O)CCOC2=C1 JOXZTUJZGKRJGL-UHFFFAOYSA-N 0.000 description 1
- MSTDXOZUKAQDRL-UHFFFAOYSA-N 4-Chromanone Chemical group C1=CC=C2C(=O)CCOC2=C1 MSTDXOZUKAQDRL-UHFFFAOYSA-N 0.000 description 1
- WVOIVMNXIKMNQQ-UHFFFAOYSA-N 4-[dimethylsulfamoyl(methyl)amino]-2,2-dimethyl-3,4-dihydrochromene-6-carbonitrile Chemical compound C1=C(C#N)C=C2C(N(C)S(=O)(=O)N(C)C)CC(C)(C)OC2=C1 WVOIVMNXIKMNQQ-UHFFFAOYSA-N 0.000 description 1
- MKQQHQNLVTZYFF-UHFFFAOYSA-N 4-[dimethylsulfamoyl(methyl)amino]-2,2-dimethyl-3,4-dihydrochromene-6-carboxamide Chemical compound C1=C(C(N)=O)C=C2C(N(C)S(=O)(=O)N(C)C)CC(C)(C)OC2=C1 MKQQHQNLVTZYFF-UHFFFAOYSA-N 0.000 description 1
- RBXNUZWQGXHBNL-UHFFFAOYSA-N 4-[dimethylsulfamoyl(methyl)amino]-2,2-dimethyl-3,4-dihydrochromene-6-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2C(N(C)S(=O)(=O)N(C)C)CC(C)(C)OC2=C1 RBXNUZWQGXHBNL-UHFFFAOYSA-N 0.000 description 1
- OJYUPUBGYGZVNI-UHFFFAOYSA-N 4-[ethylsulfonyl(4,4,4-trifluorobutyl)amino]-2,2-dimethyl-3,4-dihydrochromene-6-carboxamide Chemical compound C1=C(C(N)=O)C=C2C(N(CCCC(F)(F)F)S(=O)(=O)CC)CC(C)(C)OC2=C1 OJYUPUBGYGZVNI-UHFFFAOYSA-N 0.000 description 1
- FSZKETKIAORPOU-UHFFFAOYSA-N 4-[ethylsulfonyl(4,4,4-trifluorobutyl)amino]-2,2-dimethyl-3,4-dihydrochromene-6-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2C(N(CCCC(F)(F)F)S(=O)(=O)CC)CC(C)(C)OC2=C1 FSZKETKIAORPOU-UHFFFAOYSA-N 0.000 description 1
- KJOLLDGKGGVXHG-UHFFFAOYSA-N 4-[ethylsulfonyl(methyl)amino]-2,2-dimethyl-3,4-dihydrochromene-6-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2C(N(C)S(=O)(=O)CC)CC(C)(C)OC2=C1 KJOLLDGKGGVXHG-UHFFFAOYSA-N 0.000 description 1
- OKIIAJVCQJBKPU-UHFFFAOYSA-N 4-[ethylsulfonyl(pyridin-4-ylmethyl)amino]-2,2-dimethyl-3,4-dihydrochromene-6-carboxamide Chemical compound C1C(C)(C)OC2=CC=C(C(N)=O)C=C2C1N(S(=O)(=O)CC)CC1=CC=NC=C1 OKIIAJVCQJBKPU-UHFFFAOYSA-N 0.000 description 1
- MPCWGJKKSRALIJ-UHFFFAOYSA-N 4-[ethylsulfonyl(pyridin-4-ylmethyl)amino]-2,2-dimethyl-3,4-dihydrochromene-6-carboxylic acid Chemical compound C1C(C)(C)OC2=CC=C(C(O)=O)C=C2C1N(S(=O)(=O)CC)CC1=CC=NC=C1 MPCWGJKKSRALIJ-UHFFFAOYSA-N 0.000 description 1
- GDBUZIKSJGRBJP-UHFFFAOYSA-N 4-acetoxy benzoic acid Chemical compound CC(=O)OC1=CC=C(C(O)=O)C=C1 GDBUZIKSJGRBJP-UHFFFAOYSA-N 0.000 description 1
- KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
- RHMPLDJJXGPMEX-UHFFFAOYSA-N 4-fluorophenol Chemical compound OC1=CC=C(F)C=C1 RHMPLDJJXGPMEX-UHFFFAOYSA-N 0.000 description 1
- TXFJMSQAYBRSRI-UHFFFAOYSA-N 6-(4-bromophenyl)-2,2-dimethyl-3,4-dihydrochromen-4-amine;hydrochloride Chemical compound Cl.C=1C=C2OC(C)(C)CC(N)C2=CC=1C1=CC=C(Br)C=C1 TXFJMSQAYBRSRI-UHFFFAOYSA-N 0.000 description 1
- LLWCBPNSRBRTGN-UHFFFAOYSA-N 6-fluoro-2,2-dimethyl-3,4-dihydrochromen-4-amine Chemical compound FC1=CC=C2OC(C)(C)CC(N)C2=C1 LLWCBPNSRBRTGN-UHFFFAOYSA-N 0.000 description 1
- ZKJHJJCSEUDVCQ-UHFFFAOYSA-N 6-fluoro-2,2-dimethyl-7-pyrrolidin-1-yl-3,4-dihydrochromen-4-amine;dihydrochloride Chemical compound Cl.Cl.C1=C2OC(C)(C)CC(N)C2=CC(F)=C1N1CCCC1 ZKJHJJCSEUDVCQ-UHFFFAOYSA-N 0.000 description 1
- SWBBIJZMIGAZHW-UHFFFAOYSA-N 6-fluoro-2,3-dihydrochromen-4-one Chemical compound O1CCC(=O)C2=CC(F)=CC=C21 SWBBIJZMIGAZHW-UHFFFAOYSA-N 0.000 description 1
- WVQYSVLMDHXHOV-UHFFFAOYSA-N 6-fluoro-3,4-dihydro-2h-chromen-4-amine Chemical compound C1=C(F)C=C2C(N)CCOC2=C1 WVQYSVLMDHXHOV-UHFFFAOYSA-N 0.000 description 1
- VHMBQKMHABXVJN-UHFFFAOYSA-N 6-fluoro-3,4-dihydro-2h-chromen-4-amine;hydrochloride Chemical compound Cl.C1=C(F)C=C2C(N)CCOC2=C1 VHMBQKMHABXVJN-UHFFFAOYSA-N 0.000 description 1
- FYXPWIUHWKJSSP-UHFFFAOYSA-N 6-methoxy-2,2-dimethyl-3,4-dihydrochromen-4-amine;hydrochloride Chemical compound Cl.O1C(C)(C)CC(N)C2=CC(OC)=CC=C21 FYXPWIUHWKJSSP-UHFFFAOYSA-N 0.000 description 1
- DLQGWNBLQDVNFX-UHFFFAOYSA-N 6-phenyl-2,3-dihydrochromen-4-one Chemical compound C1=C2C(=O)CCOC2=CC=C1C1=CC=CC=C1 DLQGWNBLQDVNFX-UHFFFAOYSA-N 0.000 description 1
- NKCIUOVMTURVQK-UHFFFAOYSA-N 7-chloro-6-fluoro-2,2-dimethyl-3h-chromen-4-one Chemical compound FC1=C(Cl)C=C2OC(C)(C)CC(=O)C2=C1 NKCIUOVMTURVQK-UHFFFAOYSA-N 0.000 description 1
- QXKXYXNEOUCMIY-UHFFFAOYSA-N 7-methoxy-2,2-dimethyl-3h-chromen-4-one Chemical compound O=C1CC(C)(C)OC2=CC(OC)=CC=C21 QXKXYXNEOUCMIY-UHFFFAOYSA-N 0.000 description 1
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 206010003130 Arrhythmia supraventricular Diseases 0.000 description 1
- YNPDFBFVMJNGKZ-UHFFFAOYSA-N BTB10270 Natural products CC(=O)C1=CC(C)=CC=C1O YNPDFBFVMJNGKZ-UHFFFAOYSA-N 0.000 description 1
- KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical compound C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 206010049993 Cardiac death Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- OCUCCJIRFHNWBP-IYEMJOQQSA-L Copper gluconate Chemical class [Cu+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O OCUCCJIRFHNWBP-IYEMJOQQSA-L 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 206010011906 Death Diseases 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- 108010061435 Enalapril Proteins 0.000 description 1
- 241000501667 Etroplus Species 0.000 description 1
- 238000005863 Friedel-Crafts acylation reaction Methods 0.000 description 1
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
- 238000005618 Fries rearrangement reaction Methods 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 229940122957 Histamine H2 receptor antagonist Drugs 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101001047090 Homo sapiens Potassium voltage-gated channel subfamily H member 2 Proteins 0.000 description 1
- 206010021118 Hypotonia Diseases 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 229910010084 LiAlH4 Inorganic materials 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- ZKGNPQKYVKXMGJ-UHFFFAOYSA-N N,N-dimethylacetamide Chemical compound CN(C)C(C)=O.CN(C)C(C)=O ZKGNPQKYVKXMGJ-UHFFFAOYSA-N 0.000 description 1
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- LOVYYPPJQRFHKS-UHFFFAOYSA-N O1C(C)(C)CC(=NO)C2=C1C=C(OC)C(OC)=C2 Chemical compound O1C(C)(C)CC(=NO)C2=C1C=C(OC)C(OC)=C2 LOVYYPPJQRFHKS-UHFFFAOYSA-N 0.000 description 1
- 102000004257 Potassium Channel Human genes 0.000 description 1
- 229940127315 Potassium Channel Openers Drugs 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 235000019486 Sunflower oil Nutrition 0.000 description 1
- 239000000150 Sympathomimetic Substances 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 241000269368 Xenopus laevis Species 0.000 description 1
- PZPSICDSQWAIBR-UHFFFAOYSA-N [4-(4-bromophenyl)phenyl] acetate Chemical group C1=CC(OC(=O)C)=CC=C1C1=CC=C(Br)C=C1 PZPSICDSQWAIBR-UHFFFAOYSA-N 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 230000036982 action potential Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001346 alkyl aryl ethers Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229960000212 aminophenazone Drugs 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- WFKAJVHLWXSISD-UHFFFAOYSA-N anhydrous dimethyl-acetamide Natural products CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 230000001142 anti-diarrhea Effects 0.000 description 1
- 230000003440 anti-fibrillation Effects 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000003699 antiulcer agent Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 238000006172 aromatic nitration reaction Methods 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000001746 atrial effect Effects 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 150000001562 benzopyrans Chemical class 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 1
- CJGYSWNGNKCJSB-YVLZZHOMSA-N bucladesine Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](OC(=O)CCC)[C@@H]2N1C(N=CN=C2NC(=O)CCC)=C2N=C1 CJGYSWNGNKCJSB-YVLZZHOMSA-N 0.000 description 1
- 229960005263 bucladesine Drugs 0.000 description 1
- WEDIIKBPDQQQJU-UHFFFAOYSA-N butane-1-sulfonyl chloride Chemical compound CCCCS(Cl)(=O)=O WEDIIKBPDQQQJU-UHFFFAOYSA-N 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 235000011116 calcium hydroxide Nutrition 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 229960000830 captopril Drugs 0.000 description 1
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 210000004413 cardiac myocyte Anatomy 0.000 description 1
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 125000004965 chloroalkyl group Chemical group 0.000 description 1
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 1
- VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical compound C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 1
- 229960001380 cimetidine Drugs 0.000 description 1
- CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 description 1
- 229940082627 class iii antiarrhythmics Drugs 0.000 description 1
- 239000003026 cod liver oil Substances 0.000 description 1
- 235000012716 cod liver oil Nutrition 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000005595 deprotonation Effects 0.000 description 1
- 238000010537 deprotonation reaction Methods 0.000 description 1
- 150000001983 dialkylethers Chemical class 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 229940082657 digitalis glycosides Drugs 0.000 description 1
- 125000006263 dimethyl aminosulfonyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- IXTMWRCNAAVVAI-UHFFFAOYSA-N dofetilide Chemical compound C=1C=C(NS(C)(=O)=O)C=CC=1CCN(C)CCOC1=CC=C(NS(C)(=O)=O)C=C1 IXTMWRCNAAVVAI-UHFFFAOYSA-N 0.000 description 1
- 229960002994 dofetilide Drugs 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000013583 drug formulation Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000007831 electrophysiology Effects 0.000 description 1
- 238000002001 electrophysiology Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 229960000873 enalapril Drugs 0.000 description 1
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 1
- 238000003821 enantio-separation Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- XUFQPHANEAPEMJ-UHFFFAOYSA-N famotidine Chemical compound NC(N)=NC1=NC(CSCCC(N)=NS(N)(=O)=O)=CS1 XUFQPHANEAPEMJ-UHFFFAOYSA-N 0.000 description 1
- 229960001596 famotidine Drugs 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000002599 gastric fundus Anatomy 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 230000000762 glandular Effects 0.000 description 1
- 229960004580 glibenclamide Drugs 0.000 description 1
- ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 150000002440 hydroxy compounds Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000002102 hyperpolarization Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 1
- 150000003893 lactate salts Chemical class 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000014380 magnesium carbonate Nutrition 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- 235000012245 magnesium oxide Nutrition 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- 150000004701 malic acid derivatives Chemical class 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000010907 mechanical stirring Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- JUAMBJSJMUVASC-UHFFFAOYSA-N methyl 4-[ethylsulfonyl(pyridin-4-ylmethyl)amino]-2,2-dimethyl-3,4-dihydrochromene-6-carboxylate Chemical compound C1C(C)(C)OC2=CC=C(C(=O)OC)C=C2C1N(S(=O)(=O)CC)CC1=CC=NC=C1 JUAMBJSJMUVASC-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 150000004712 monophosphates Chemical class 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 230000004118 muscle contraction Effects 0.000 description 1
- 230000036640 muscle relaxation Effects 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- GKBAWFXOKVYCEM-UHFFFAOYSA-N n-(2,2,6,7-tetramethyl-3,4-dihydrochromen-3-yl)ethanesulfonamide Chemical compound CC1=C(C)C=C2OC(C)(C)C(NS(=O)(=O)CC)CC2=C1 GKBAWFXOKVYCEM-UHFFFAOYSA-N 0.000 description 1
- QWRFDVPFTMYBQB-UHFFFAOYSA-N n-(2,2,6,7-tetramethyl-3h-chromen-4-ylidene)hydroxylamine Chemical compound O1C(C)(C)CC(=NO)C2=C1C=C(C)C(C)=C2 QWRFDVPFTMYBQB-UHFFFAOYSA-N 0.000 description 1
- QXDKURCWIRRHJS-UHFFFAOYSA-N n-(2,2,6-trimethyl-3,4-dihydrochromen-4-yl)ethanesulfonamide Chemical compound C1=C(C)C=C2C(NS(=O)(=O)CC)CC(C)(C)OC2=C1 QXDKURCWIRRHJS-UHFFFAOYSA-N 0.000 description 1
- FJBRRGPIEUTHPB-UHFFFAOYSA-N n-(6,8-difluoro-2,2-dimethyl-3h-chromen-4-ylidene)hydroxylamine Chemical compound FC1=CC(F)=C2OC(C)(C)CC(=NO)C2=C1 FJBRRGPIEUTHPB-UHFFFAOYSA-N 0.000 description 1
- WCSSTKFXFSZDMA-UHFFFAOYSA-N n-(6-cyano-2,2-dimethyl-3,4-dihydrochromen-4-yl)-n-(4,4,4-trifluorobutyl)ethanesulfonamide Chemical compound C1=C(C#N)C=C2C(N(CCCC(F)(F)F)S(=O)(=O)CC)CC(C)(C)OC2=C1 WCSSTKFXFSZDMA-UHFFFAOYSA-N 0.000 description 1
- HEQPLVRXTJYCRD-UHFFFAOYSA-N n-(6-fluoro-2,2-dimethyl-3,4-dihydrochromen-4-yl)ethanesulfonamide Chemical compound C1=C(F)C=C2C(NS(=O)(=O)CC)CC(C)(C)OC2=C1 HEQPLVRXTJYCRD-UHFFFAOYSA-N 0.000 description 1
- GQYWWZISGWDNRQ-UHFFFAOYSA-N n-(7-methoxy-2,2-dimethyl-3,4-dihydrochromen-3-yl)ethanesulfonamide Chemical compound C1=C(OC)C=C2OC(C)(C)C(NS(=O)(=O)CC)CC2=C1 GQYWWZISGWDNRQ-UHFFFAOYSA-N 0.000 description 1
- RRIQBEPRIKELDB-UHFFFAOYSA-N n-(7-methoxy-2,2-dimethyl-3,4-dihydrochromen-3-yl)methanesulfonamide Chemical compound C1C(NS(C)(=O)=O)C(C)(C)OC2=CC(OC)=CC=C21 RRIQBEPRIKELDB-UHFFFAOYSA-N 0.000 description 1
- XHFLQLXESPFWLE-UHFFFAOYSA-N n-(7-methoxy-2,2-dimethyl-3h-chromen-4-ylidene)hydroxylamine Chemical compound ON=C1CC(C)(C)OC2=CC(OC)=CC=C21 XHFLQLXESPFWLE-UHFFFAOYSA-N 0.000 description 1
- BASAUWFNEPUJDQ-ZMBIFBSDSA-N n-[1'-[(2r)-6-cyano-1,2,3,4-tetrahydronaphthalen-2-yl]-4-oxospiro[3h-chromene-2,4'-piperidine]-6-yl]methanesulfonamide;hydron;chloride Chemical compound Cl.C1CC2=CC(C#N)=CC=C2C[C@@H]1N(CC1)CCC11OC2=CC=C(NS(=O)(=O)C)C=C2C(=O)C1 BASAUWFNEPUJDQ-ZMBIFBSDSA-N 0.000 description 1
- QSPPRYLTQFCUCH-UHFFFAOYSA-N n-methylethanesulfonamide Chemical compound CCS(=O)(=O)NC QSPPRYLTQFCUCH-UHFFFAOYSA-N 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 239000012053 oil suspension Substances 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000036284 oxygen consumption Effects 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 230000009090 positive inotropic effect Effects 0.000 description 1
- 108020001213 potassium channel Proteins 0.000 description 1
- 239000003450 potassium channel blocker Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- JCWLEWKPXYZHGQ-UHFFFAOYSA-N propan-2-yl 2-bromoacetate Chemical compound CC(C)OC(=O)CBr JCWLEWKPXYZHGQ-UHFFFAOYSA-N 0.000 description 1
- DRINJBFRTLBHNF-UHFFFAOYSA-N propane-2-sulfonyl chloride Chemical compound CC(C)S(Cl)(=O)=O DRINJBFRTLBHNF-UHFFFAOYSA-N 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 229960003401 ramipril Drugs 0.000 description 1
- HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 description 1
- VMXUWOKSQNHOCA-LCYFTJDESA-N ranitidine Chemical compound [O-][N+](=O)/C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 VMXUWOKSQNHOCA-LCYFTJDESA-N 0.000 description 1
- 229960000620 ranitidine Drugs 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 230000002336 repolarization Effects 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 230000000580 secretagogue effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000000050 smooth muscle relaxant Substances 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 238000005556 structure-activity relationship Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000002600 sunflower oil Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000001975 sympathomimetic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
-
- 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
- A61P1/12—Antidiarrhoeals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- A61P9/06—Antiarrhythmics
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C07D311/68—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with nitrogen atoms directly attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C07D311/70—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with two hydrocarbon radicals attached in position 2 and elements other than carbon and hydrogen in position 6
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrane Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Saccharide Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19619614A DE19619614A1 (de) | 1996-05-15 | 1996-05-15 | Sulfonamid-substituierte Chromane, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
DE1996139462 DE19639462A1 (de) | 1996-09-26 | 1996-09-26 | Sulfonamid-substituierte Chromane, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
Publications (3)
Publication Number | Publication Date |
---|---|
NO972211D0 NO972211D0 (no) | 1997-05-14 |
NO972211L NO972211L (no) | 1997-11-17 |
NO315556B1 true NO315556B1 (no) | 2003-09-22 |
Family
ID=26025736
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO19972211A NO315556B1 (no) | 1996-05-15 | 1997-05-14 | Kromaner, deres fremstilling og anvendelse samt medikamenter inneholdende forbindelsene |
Country Status (24)
Country | Link |
---|---|
EP (1) | EP0807629B1 (pt) |
JP (1) | JP4234798B2 (pt) |
KR (1) | KR100547921B1 (pt) |
CN (1) | CN1204134C (pt) |
AR (2) | AR007115A1 (pt) |
AT (1) | ATE260909T1 (pt) |
AU (1) | AU711986B2 (pt) |
BR (1) | BR9703161A (pt) |
CA (1) | CA2205477A1 (pt) |
CZ (1) | CZ149497A3 (pt) |
DE (1) | DE59711352D1 (pt) |
DK (1) | DK0807629T3 (pt) |
ES (1) | ES2218617T3 (pt) |
HK (1) | HK1006640A1 (pt) |
HR (1) | HRP970255B1 (pt) |
HU (1) | HUP9700903A3 (pt) |
IL (1) | IL120827A (pt) |
NO (1) | NO315556B1 (pt) |
NZ (1) | NZ314800A (pt) |
PL (1) | PL191330B1 (pt) |
PT (1) | PT807629E (pt) |
SK (1) | SK283837B6 (pt) |
TR (1) | TR199700369A2 (pt) |
TW (1) | TW496866B (pt) |
Families Citing this family (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NZ329200A (en) * | 1996-12-16 | 1999-05-28 | Hoechst Ag | Sulphonamide substituted quinazoline, isoquinoline, quinoline or benzo[1,3-]oxazine derivatives and medicaments |
DE19705133A1 (de) * | 1997-02-11 | 1998-08-13 | Hoechst Ag | Sulfonamid-substituierte Verbindungen, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
DE19706675A1 (de) * | 1997-02-20 | 1998-08-27 | Hoechst Ag | Sulfonamid-substituierte Chromane, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
EP0895994A3 (de) | 1997-08-05 | 1999-12-15 | Hoechst Marion Roussel Deutschland GmbH | Sulfonamid-substituierte Pyranopyridine, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament |
DE19742509A1 (de) * | 1997-09-26 | 1999-04-01 | Hoechst Marion Roussel De Gmbh | Sulfonamid-substituierte Chromane, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltende pharmazeutische Zubereitungen |
DE19742508A1 (de) * | 1997-09-26 | 1999-04-01 | Hoechst Marion Roussel De Gmbh | Sulfonamid-substituierte Chromane, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltende pharmazeutische Zubereitungen |
DE19748469A1 (de) * | 1997-11-03 | 1999-05-06 | Hoechst Marion Roussel De Gmbh | Sulfonamid-substituierte Benzopyranderivate, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament sowie sie enthaltende pharmazeutische Zubereitungen |
CA2341678C (en) | 1998-09-01 | 2009-10-13 | Bristol-Myers Squibb Company | Potassium channel inhibitors and method |
DE19858253A1 (de) | 1998-12-17 | 2000-06-21 | Aventis Pharma Gmbh | Verwendung von Inhibitoren des KQt1-Kanals zur Herstellung eines Medikaments zur Behandlung von Krankheiten, die durch Helminthen und Ektoparasiten hervorgerufen werden |
US7368582B2 (en) | 2003-10-17 | 2008-05-06 | Solvay Pharmaceuticals Gmbh | Amidomethyl-substituted 2-(4-sulfonylamino)-3-hydroxy-3,4-dihydro-2H-chromen-6-yl compounds, a process and intermediates for their production, and pharmaceutical compositions containing them |
WO2005090357A1 (en) * | 2004-03-23 | 2005-09-29 | Nissan Chemical Industries, Ltd. | Tricyclic benzopyran compound as anti-arrhythmic agents |
US7884109B2 (en) | 2005-04-05 | 2011-02-08 | Wyeth Llc | Purine and imidazopyridine derivatives for immunosuppression |
US7989459B2 (en) | 2006-02-17 | 2011-08-02 | Pharmacopeia, Llc | Purinones and 1H-imidazopyridinones as PKC-theta inhibitors |
AR063142A1 (es) | 2006-10-04 | 2008-12-30 | Pharmacopeia Inc | Derivados de 2-(bencimidazolil) purina y purinonas 6-sustituidas utiles como inmunosupresores,y composiciones farmaceuticas que los contienen. |
US7915268B2 (en) | 2006-10-04 | 2011-03-29 | Wyeth Llc | 8-substituted 2-(benzimidazolyl)purine derivatives for immunosuppression |
US7902187B2 (en) | 2006-10-04 | 2011-03-08 | Wyeth Llc | 6-substituted 2-(benzimidazolyl)purine and purinone derivatives for immunosuppression |
CN102414213B (zh) * | 2009-04-30 | 2014-12-24 | 日产化学工业株式会社 | 三环苯并吡喃化合物的新的晶形及其制造方法 |
TWI583677B (zh) * | 2012-09-21 | 2017-05-21 | 日本臟器製藥股份有限公司 | 香豆素衍生物 |
CN103012380B (zh) * | 2013-01-10 | 2015-03-04 | 山东大学 | 一种色满类化合物及其制备方法与应用 |
JP6089055B2 (ja) * | 2014-03-20 | 2017-03-01 | 日本臓器製薬株式会社 | クマリン誘導体を含有する医薬 |
AR117169A1 (es) | 2018-11-28 | 2021-07-14 | Bayer Ag | (tio)amidas de piridazina como compuestos fungicidas |
EP4146628A1 (en) | 2020-05-06 | 2023-03-15 | Bayer Aktiengesellschaft | Pyridine (thio)amides as fungicidal compounds |
US20230180756A1 (en) | 2020-05-12 | 2023-06-15 | Bayer Aktiengesellschaft | Triazine and pyrimidine (thio)amides as fungicidal compounds |
BR112022023550A2 (pt) | 2020-05-19 | 2023-01-03 | Bayer Cropscience Ag | (tio)amidas azabicíclicas como compostos fungicidas |
EP4156936A1 (en) | 2020-05-27 | 2023-04-05 | Bayer Aktiengesellschaft | Active compound combinations |
WO2023078915A1 (en) | 2021-11-03 | 2023-05-11 | Bayer Aktiengesellschaft | Bis(hetero)aryl thioether (thio)amides as fungicidal compounds |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3737195A1 (de) * | 1987-11-03 | 1989-05-18 | Bayer Ag | Chromanderivate, verfahren zu ihrer herstellung und ihre verwendung in arzneimitteln |
FR2639349B1 (fr) * | 1988-11-23 | 1991-02-22 | Sanofi Sa | Nouveaux derives du chromane actifs sur le systeme nerveux central, leur procede de preparation et les compositions pharmaceutiques en contenant |
US5104890A (en) * | 1989-03-28 | 1992-04-14 | Fujisawa Pharmaceutical Company, Ltd. | Benzopyran derivatives and processes for preparation thereof |
-
1997
- 1997-05-13 PT PT97107775T patent/PT807629E/pt unknown
- 1997-05-13 ES ES97107775T patent/ES2218617T3/es not_active Expired - Lifetime
- 1997-05-13 HR HR970255A patent/HRP970255B1/xx not_active IP Right Cessation
- 1997-05-13 TR TR97/00369A patent/TR199700369A2/xx unknown
- 1997-05-13 DE DE59711352T patent/DE59711352D1/de not_active Expired - Lifetime
- 1997-05-13 AT AT97107775T patent/ATE260909T1/de not_active IP Right Cessation
- 1997-05-13 AU AU20806/97A patent/AU711986B2/en not_active Ceased
- 1997-05-13 NZ NZ314800A patent/NZ314800A/xx unknown
- 1997-05-13 AR ARP970101998A patent/AR007115A1/es not_active Application Discontinuation
- 1997-05-13 SK SK603-97A patent/SK283837B6/sk unknown
- 1997-05-13 EP EP97107775A patent/EP0807629B1/de not_active Expired - Lifetime
- 1997-05-13 DK DK97107775T patent/DK0807629T3/da active
- 1997-05-13 TW TW086106326A patent/TW496866B/zh not_active IP Right Cessation
- 1997-05-13 CN CNB971115400A patent/CN1204134C/zh not_active Expired - Fee Related
- 1997-05-14 JP JP13798497A patent/JP4234798B2/ja not_active Expired - Fee Related
- 1997-05-14 NO NO19972211A patent/NO315556B1/no unknown
- 1997-05-14 CZ CZ971494A patent/CZ149497A3/cs unknown
- 1997-05-14 BR BR9703161A patent/BR9703161A/pt not_active Application Discontinuation
- 1997-05-14 IL IL12082797A patent/IL120827A/en not_active IP Right Cessation
- 1997-05-15 PL PL319995A patent/PL191330B1/pl unknown
- 1997-05-15 KR KR10-1997-0018635A patent/KR100547921B1/ko not_active IP Right Cessation
- 1997-05-15 HU HU9700903A patent/HUP9700903A3/hu unknown
- 1997-05-15 CA CA002205477A patent/CA2205477A1/en not_active Abandoned
- 1997-11-26 AR ARP970105574A patent/AR010314A1/es unknown
-
1998
- 1998-06-23 HK HK98106052A patent/HK1006640A1/xx not_active IP Right Cessation
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
NO315556B1 (no) | Kromaner, deres fremstilling og anvendelse samt medikamenter inneholdende forbindelsene | |
EP2796450B1 (en) | 6-aminopyridine-3-ol derivatives or pharmaceutically acceptable salts thereof, and pharmaceutical composition containing same as active ingredients for preventing or treating diseases caused by angiogenesis | |
EP0906911B1 (de) | Sulfonamid-substituierte Chromane (K+Kanal-Blocker), Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament sowie sie enthaltende pharmazeutische Zubereitungen | |
US6191164B1 (en) | Sulfonamide-substituted chromans, processes for their preparation, their use as a medicament or diagnostic, and medicament comprising them | |
EP0913396B1 (de) | Sulfonamid-substituierte Benzopyranderivate, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament sowie sie enthaltende pharmazeutische Zubereitungen | |
KR19980071530A (ko) | 설폰아미드-치환된 크로만, 이의 제조방법, 약제 또는 진단 보조제로서의 이의 용도, 및 이를 포함하는 약제 | |
NO312546B1 (no) | Sulfonamidsubstituerte kondenserte 5-ringforbindelser, deres anvendelse til fremstilling av medikament samt farmasöytiskepreparater inneholdende forbindelsene | |
EP0861836B1 (de) | Sulfonamid-substituierte anellierte 7-Ring-Verbindungen mit Kaliumkanal blockierender Wirkung | |
WO2010008746A1 (en) | Pharmaceutical compositions and methods for treating age-related macular degeneration with melatonin analogues | |
AU727216B2 (en) | Sulfonamide-substituted compounds, processes for their preparation, their use as a medicament or diagnostic, and medicament comprising them | |
NO319563B1 (no) | Sulfonamidsubstituerte kromaner, deres anvendelse som medikament samt farmasoytiske preparater inneholdende forbindelsene. | |
US6333349B1 (en) | Sulfonamide-substituted fused 7-membered ring compounds, their use as a medicament, and pharmaceutical preparations comprising them | |
MXPA97003534A (en) | Chromants replaced with sulfonamide, procedure for preparation, employment as a medicinal or diagnostic agent, and as a medication that conti | |
WO2002036568A1 (en) | N-type calcium channel antagonists for the treatment of pain | |
DE19619614A1 (de) | Sulfonamid-substituierte Chromane, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament | |
DE19639462A1 (de) | Sulfonamid-substituierte Chromane, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltendes Medikament | |
CN107652194A (zh) | 一类用于治疗神经系统疾病的新化合物 |