IL120827A

IL120827A - Sulfonamide-substituted chromans, processes for their preparation, and medicaments comprising them

Sulfonamide-substituted chromans, processes for their preparation, and medicaments comprising them

Info

Publication number: IL120827A
Authority: IL; Israel
Prior art keywords: amino; methyl; ethylsulfonyl; dimethylchroman; formula
Prior art date: 1996-05-15

Application number

IL12082797A

Other languages

English (en)

Other versions

IL120827A0 (en

Original Assignee

Hoechst Ag

Priority date

1996-05-15

Filing date

1997-05-14

Publication date

2004-12-15

1996-05-15 Priority claimed from DE19619614A external-priority patent/DE19619614A1/de

1996-09-26 Priority claimed from DE1996139462 external-priority patent/DE19639462A1/de

1997-05-14 Application filed by Hoechst Ag filed Critical Hoechst Ag

1997-09-30 Publication of IL120827A0 publication Critical patent/IL120827A0/xx

2004-12-15 Publication of IL120827A publication Critical patent/IL120827A/en

Links

239000003814 drug Substances 0.000 title claims description 21
238000000034 method Methods 0.000 title description 192
238000002360 preparation method Methods 0.000 title description 10
230000008569 process Effects 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims description 93
239000001257 hydrogen Substances 0.000 claims description 62
229910052739 hydrogen Inorganic materials 0.000 claims description 62
-1 methoxy, sulfamoyl Chemical group 0.000 claims description 51
125000004432 carbon atom Chemical group C* 0.000 claims description 46
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 32
150000002431 hydrogen Chemical class 0.000 claims description 31
229910052740 iodine Inorganic materials 0.000 claims description 31
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 30
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
125000001424 substituent group Chemical group 0.000 claims description 26
229910052794 bromium Inorganic materials 0.000 claims description 25
125000000217 alkyl group Chemical group 0.000 claims description 24
229910052731 fluorine Inorganic materials 0.000 claims description 22
150000003839 salts Chemical class 0.000 claims description 15
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 14
229940124530 sulfonamide Drugs 0.000 claims description 12
VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical compound C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 claims description 10
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
150000003456 sulfonamides Chemical class 0.000 claims description 10
206010003119 arrhythmia Diseases 0.000 claims description 9
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 description 8
125000000753 cycloalkyl group Chemical group 0.000 claims description 8
230000006793 arrhythmia Effects 0.000 claims description 7
238000005804 alkylation reaction Methods 0.000 claims description 6
125000002947 alkylene group Chemical group 0.000 claims description 6
230000002265 prevention Effects 0.000 claims description 6
125000004076 pyridyl group Chemical group 0.000 claims description 6
210000002784 stomach Anatomy 0.000 claims description 6
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
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 5
230000027119 gastric acid secretion Effects 0.000 claims description 5
239000011734 sodium Substances 0.000 claims description 5
229910052708 sodium Inorganic materials 0.000 claims description 5
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 4
239000002168 alkylating agent Substances 0.000 claims description 4
229940100198 alkylating agent Drugs 0.000 claims description 4
230000000903 blocking effect Effects 0.000 claims description 4
125000002883 imidazolyl group Chemical group 0.000 claims description 4
230000002401 inhibitory effect Effects 0.000 claims description 4
125000005936 piperidyl group Chemical group 0.000 claims description 4
229910052700 potassium Inorganic materials 0.000 claims description 4
239000011591 potassium Substances 0.000 claims description 4
125000001544 thienyl group Chemical group 0.000 claims description 4
208000003663 ventricular fibrillation Diseases 0.000 claims description 4
206010042600 Supraventricular arrhythmias Diseases 0.000 claims description 3
208000025865 Ulcer Diseases 0.000 claims description 3
206010047281 Ventricular arrhythmia Diseases 0.000 claims description 3
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 3
125000004429 atom Chemical group 0.000 claims description 3
210000001198 duodenum Anatomy 0.000 claims description 3
238000007336 electrophilic substitution reaction Methods 0.000 claims description 3
208000021302 gastroesophageal reflux disease Diseases 0.000 claims description 3
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
230000000968 intestinal effect Effects 0.000 claims description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
208000000689 peptic esophagitis Diseases 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
231100000397 ulcer Toxicity 0.000 claims description 3
230000002861 ventricular Effects 0.000 claims description 3
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 2
230000000741 diarrhetic effect Effects 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
125000005956 isoquinolyl group Chemical group 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
125000005493 quinolyl group Chemical group 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
238000002844 melting Methods 0.000 description 157
230000008018 melting Effects 0.000 description 157
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
239000000126 substance Substances 0.000 description 63
239000000047 product Substances 0.000 description 59
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 55
239000002904 solvent Substances 0.000 description 55
239000000203 mixture Substances 0.000 description 51
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 48
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 42
238000006243 chemical reaction Methods 0.000 description 42
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
239000013078 crystal Substances 0.000 description 39
108091006146 Channels Proteins 0.000 description 36
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 36
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
239000003921 oil Substances 0.000 description 30
235000019198 oils Nutrition 0.000 description 30
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
239000000243 solution Substances 0.000 description 27
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 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 23
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
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
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 19
230000009471 action Effects 0.000 description 19
238000009903 catalytic hydrogenation reaction Methods 0.000 description 19
FRYHCSODNHYDPU-UHFFFAOYSA-N ethanesulfonyl chloride Chemical compound CCS(Cl)(=O)=O FRYHCSODNHYDPU-UHFFFAOYSA-N 0.000 description 19
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
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
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 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 13
239000012312 sodium hydride Substances 0.000 description 13
238000010626 work up procedure Methods 0.000 description 13
LNDGACQEAYKNOI-UHFFFAOYSA-N 1,1,1-trifluoro-4-iodobutane Chemical compound FC(F)(F)CCCI LNDGACQEAYKNOI-UHFFFAOYSA-N 0.000 description 12
238000004821 distillation Methods 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
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
238000002425 crystallisation Methods 0.000 description 9
230000008025 crystallization Effects 0.000 description 9
238000001914 filtration Methods 0.000 description 9
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 8
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
238000004440 column chromatography Methods 0.000 description 8
239000003480 eluent Substances 0.000 description 8
239000007788 liquid Substances 0.000 description 8
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 8
238000000746 purification Methods 0.000 description 8
239000011541 reaction mixture Substances 0.000 description 8
238000003756 stirring Methods 0.000 description 8
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 7
229910000564 Raney nickel Inorganic materials 0.000 description 7
229910021529 ammonia Inorganic materials 0.000 description 7
KMGBZBJJOKUPIA-UHFFFAOYSA-N butyl iodide Chemical compound CCCCI KMGBZBJJOKUPIA-UHFFFAOYSA-N 0.000 description 7
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 7
238000004587 chromatography analysis Methods 0.000 description 7
239000012230 colorless oil Substances 0.000 description 7
230000005764 inhibitory process Effects 0.000 description 7
239000002244 precipitate Substances 0.000 description 7
239000007787 solid Substances 0.000 description 7
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 6
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
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 6
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
239000007868 Raney catalyst Substances 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
150000001412 amines Chemical class 0.000 description 6
230000003288 anthiarrhythmic effect Effects 0.000 description 6
239000003054 catalyst Substances 0.000 description 6
238000001816 cooling Methods 0.000 description 6
238000000354 decomposition reaction Methods 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
239000012074 organic phase Substances 0.000 description 6
150000002923 oximes Chemical class 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
241000283973 Oryctolagus cuniculus Species 0.000 description 5
238000009825 accumulation Methods 0.000 description 5
239000002585 base Substances 0.000 description 5
239000003795 chemical substances by application Substances 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
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
210000000287 oocyte Anatomy 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
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 4
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 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 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
229960000212 aminophenazone Drugs 0.000 description 4
239000003416 antiarrhythmic agent Substances 0.000 description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
229960004132 diethyl ether Drugs 0.000 description 4
230000000694 effects Effects 0.000 description 4
239000007789 gas Substances 0.000 description 4
230000000762 glandular Effects 0.000 description 4
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 4
238000002955 isolation Methods 0.000 description 4
230000007246 mechanism Effects 0.000 description 4
239000001301 oxygen Substances 0.000 description 4
229910052760 oxygen Inorganic materials 0.000 description 4
239000003208 petroleum Substances 0.000 description 4
239000000546 pharmaceutical excipient Substances 0.000 description 4
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
230000009467 reduction 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
VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-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
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
TVZCRIROJQEVOT-CABCVRRESA-N Cromakalim Chemical group N1([C@@H]2C3=CC(=CC=C3OC([C@H]2O)(C)C)C#N)CCCC1=O TVZCRIROJQEVOT-CABCVRRESA-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
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
241000269370 Xenopus <genus> Species 0.000 description 3
239000002253 acid Substances 0.000 description 3
230000029936 alkylation Effects 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
239000000460 chlorine Substances 0.000 description 3
229910052801 chlorine Inorganic materials 0.000 description 3
229950004210 cromakalim Drugs 0.000 description 3
238000001035 drying Methods 0.000 description 3
238000010828 elution Methods 0.000 description 3
239000003995 emulsifying agent Substances 0.000 description 3
230000002496 gastric effect Effects 0.000 description 3
239000008103 glucose Substances 0.000 description 3
238000011534 incubation Methods 0.000 description 3
239000003112 inhibitor Substances 0.000 description 3
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 3
239000000155 melt Substances 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
150000003053 piperidines Chemical class 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
230000003389 potentiating effect Effects 0.000 description 3
230000002829 reductive effect Effects 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
SJMMFGNAJFFWNL-UHFFFAOYSA-N (2,4-difluorophenyl) acetate Chemical compound CC(=O)OC1=CC=C(F)C=C1F SJMMFGNAJFFWNL-UHFFFAOYSA-N 0.000 description 2
OSKGYRIYNMZFSJ-UHFFFAOYSA-N (3,4-dichlorophenyl) acetate Chemical compound CC(=O)OC1=CC=C(Cl)C(Cl)=C1 OSKGYRIYNMZFSJ-UHFFFAOYSA-N 0.000 description 2
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
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