CZ149497A3 - Chromans, process of their preparation, medicaments in which they are comprised and their use - Google Patents
Chromans, process of their preparation, medicaments in which they are comprised and their use Download PDFInfo
- Publication number
- CZ149497A3 CZ149497A3 CZ971494A CZ149497A CZ149497A3 CZ 149497 A3 CZ149497 A3 CZ 149497A3 CZ 971494 A CZ971494 A CZ 971494A CZ 149497 A CZ149497 A CZ 149497A CZ 149497 A3 CZ149497 A3 CZ 149497A3
- Authority
- CZ
- Czechia
- Prior art keywords
- group
- amino
- dimethylchroman
- atom
- methyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 29
- 239000003814 drug Substances 0.000 title claims description 27
- 238000002360 preparation method Methods 0.000 title claims description 25
- 230000008569 process Effects 0.000 title description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 175
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 37
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 32
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 32
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 32
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 29
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 18
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 14
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 12
- 125000002252 acyl group Chemical group 0.000 claims abstract description 3
- -1 methylsulfonylamino group Chemical group 0.000 claims description 66
- 125000004432 carbon atom Chemical group C* 0.000 claims description 49
- 239000001257 hydrogen Substances 0.000 claims description 46
- 229910052739 hydrogen Inorganic materials 0.000 claims description 46
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 29
- ZCDOYSPFYFSLEW-UHFFFAOYSA-N chromate(2-) Chemical class [O-][Cr]([O-])(=O)=O ZCDOYSPFYFSLEW-UHFFFAOYSA-N 0.000 claims description 28
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 27
- 150000002431 hydrogen Chemical class 0.000 claims description 26
- 125000001424 substituent group Chemical group 0.000 claims description 25
- 125000001153 fluoro group Chemical group F* 0.000 claims description 22
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 21
- 239000000460 chlorine Substances 0.000 claims description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 17
- 239000011737 fluorine Substances 0.000 claims description 17
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 16
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 16
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 12
- 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 claims description 11
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 11
- 229940124530 sulfonamide Drugs 0.000 claims description 11
- 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 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 9
- 206010003119 arrhythmia Diseases 0.000 claims description 9
- 150000003456 sulfonamides Chemical class 0.000 claims description 9
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 8
- 238000005804 alkylation reaction Methods 0.000 claims description 7
- 230000006793 arrhythmia Effects 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 239000011734 sodium Substances 0.000 claims description 7
- PIGFYZPCRLYGLF-UHFFFAOYSA-N Aluminum nitride Chemical compound [Al]#N PIGFYZPCRLYGLF-UHFFFAOYSA-N 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 6
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 230000000903 blocking effect Effects 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 229910052708 sodium Inorganic materials 0.000 claims description 6
- 230000027119 gastric acid secretion Effects 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 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
- GIJPFQQNRIYDEG-UHFFFAOYSA-N NC1C(OC2=C(C1)C=C(C=C2)F)(C)C Chemical compound NC1C(OC2=C(C1)C=C(C=C2)F)(C)C GIJPFQQNRIYDEG-UHFFFAOYSA-N 0.000 claims description 4
- 206010049418 Sudden Cardiac Death Diseases 0.000 claims description 4
- 239000002168 alkylating agent Substances 0.000 claims description 4
- 229940100198 alkylating agent Drugs 0.000 claims description 4
- 230000029936 alkylation Effects 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 125000005936 piperidyl group Chemical group 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 210000002784 stomach Anatomy 0.000 claims description 4
- 208000003663 ventricular fibrillation Diseases 0.000 claims description 4
- MHAOGRMTYIGDML-UHFFFAOYSA-N 3-amino-2,2-dimethyl-3,4-dihydrochromene-6-carbonitrile Chemical compound C1=C(C#N)C=C2CC(N)C(C)(C)OC2=C1 MHAOGRMTYIGDML-UHFFFAOYSA-N 0.000 claims description 3
- 206010042600 Supraventricular arrhythmias Diseases 0.000 claims description 3
- 206010047281 Ventricular arrhythmia Diseases 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
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- 208000000689 peptic esophagitis Diseases 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 230000002861 ventricular Effects 0.000 claims description 3
- 206010012735 Diarrhoea Diseases 0.000 claims description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 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
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 125000005493 quinolyl group Chemical group 0.000 claims description 2
- 150000003458 sulfonic acid derivatives Chemical class 0.000 claims description 2
- 208000025865 Ulcer Diseases 0.000 claims 2
- 210000001035 gastrointestinal tract Anatomy 0.000 claims 2
- 231100000397 ulcer Toxicity 0.000 claims 2
- KGALVPYTKQIBAA-UHFFFAOYSA-N 2-methyl-3,4-dihydro-2h-chromene Chemical compound C1=CC=C2OC(C)CCC2=C1 KGALVPYTKQIBAA-UHFFFAOYSA-N 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract description 21
- 229910052736 halogen Inorganic materials 0.000 abstract description 2
- 150000002367 halogens Chemical class 0.000 abstract description 2
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 abstract 2
- 125000004422 alkyl sulphonamide group Chemical group 0.000 abstract 1
- 125000003368 amide group Chemical group 0.000 abstract 1
- 150000002148 esters Chemical class 0.000 abstract 1
- 125000003709 fluoroalkyl group Chemical group 0.000 abstract 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 abstract 1
- 239000000047 product Substances 0.000 description 160
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 69
- 239000013078 crystal Substances 0.000 description 60
- 239000007787 solid Substances 0.000 description 58
- 239000002904 solvent Substances 0.000 description 55
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 50
- 239000000203 mixture Substances 0.000 description 49
- 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
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 42
- 239000003921 oil Substances 0.000 description 41
- 235000019198 oils Nutrition 0.000 description 41
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 39
- 238000006243 chemical reaction Methods 0.000 description 38
- 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
- 238000002844 melting Methods 0.000 description 31
- 230000008018 melting Effects 0.000 description 31
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 27
- 239000000243 solution Substances 0.000 description 26
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 24
- 239000012312 sodium hydride Substances 0.000 description 24
- 229910000104 sodium hydride Inorganic materials 0.000 description 24
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 24
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 21
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 21
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 20
- 239000000725 suspension Substances 0.000 description 20
- 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
- 108091006146 Channels Proteins 0.000 description 16
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 15
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 15
- 239000003480 eluent Substances 0.000 description 14
- LNDGACQEAYKNOI-UHFFFAOYSA-N 1,1,1-trifluoro-4-iodobutane Chemical compound FC(F)(F)CCCI LNDGACQEAYKNOI-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 12
- 238000002425 crystallisation Methods 0.000 description 12
- 230000008025 crystallization Effects 0.000 description 12
- 239000000126 substance Substances 0.000 description 11
- 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
- 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 10
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 10
- WFKAJVHLWXSISD-UHFFFAOYSA-N anhydrous dimethyl-acetamide Natural products CC(C)C(N)=O WFKAJVHLWXSISD-UHFFFAOYSA-N 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-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
- 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
- 239000007868 Raney catalyst Substances 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
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 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
- 239000003054 catalyst Substances 0.000 description 7
- 239000012230 colorless oil Substances 0.000 description 7
- 238000000746 purification Methods 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
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 230000009471 action Effects 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 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
- 238000010898 silica gel chromatography Methods 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 102000004257 Potassium Channel Human genes 0.000 description 5
- 229960000212 aminophenazone Drugs 0.000 description 5
- 239000003416 antiarrhythmic agent Substances 0.000 description 5
- 239000002585 base Substances 0.000 description 5
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- 239000005457 ice water Substances 0.000 description 5
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 5
- 239000007788 liquid 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
- 239000012074 organic phase Substances 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- 108020001213 potassium channel Proteins 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 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
- 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 4
- 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 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
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 4
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- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 238000009825 accumulation Methods 0.000 description 4
- 230000003288 anthiarrhythmic effect Effects 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
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- 239000007789 gas Substances 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
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- 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 4
- 210000000287 oocyte Anatomy 0.000 description 4
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- AVQQQNCBBIEMEU-UHFFFAOYSA-N 1,1,3,3-tetramethylurea Chemical compound CN(C)C(=O)N(C)C AVQQQNCBBIEMEU-UHFFFAOYSA-N 0.000 description 3
- PBKONEOXTCPAFI-UHFFFAOYSA-N 1,2,4-trichlorobenzene Chemical compound ClC1=CC=C(Cl)C(Cl)=C1 PBKONEOXTCPAFI-UHFFFAOYSA-N 0.000 description 3
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Classifications
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
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- 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
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- 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)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (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 (1)
| Publication Number | Publication Date |
|---|---|
| CZ149497A3 true CZ149497A3 (en) | 1997-12-17 |
Family
ID=26025736
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CZ971494A CZ149497A3 (en) | 1996-05-15 | 1997-05-14 | Chromans, process of their preparation, medicaments in which they are comprised and their use |
Country Status (23)
| Country | Link |
|---|---|
| EP (1) | EP0807629B1 (enExample) |
| JP (1) | JP4234798B2 (enExample) |
| KR (1) | KR100547921B1 (enExample) |
| CN (1) | CN1204134C (enExample) |
| AR (2) | AR007115A1 (enExample) |
| AT (1) | ATE260909T1 (enExample) |
| AU (1) | AU711986B2 (enExample) |
| BR (1) | BR9703161A (enExample) |
| CA (1) | CA2205477A1 (enExample) |
| CZ (1) | CZ149497A3 (enExample) |
| DE (1) | DE59711352D1 (enExample) |
| DK (1) | DK0807629T3 (enExample) |
| ES (1) | ES2218617T3 (enExample) |
| HR (1) | HRP970255B1 (enExample) |
| HU (1) | HUP9700903A3 (enExample) |
| IL (1) | IL120827A (enExample) |
| NO (1) | NO315556B1 (enExample) |
| NZ (1) | NZ314800A (enExample) |
| PL (1) | PL191330B1 (enExample) |
| PT (1) | PT807629E (enExample) |
| SK (1) | SK283837B6 (enExample) |
| TR (1) | TR199700369A2 (enExample) |
| TW (1) | TW496866B (enExample) |
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 |
| JP2002523451A (ja) | 1998-09-01 | 2002-07-30 | ブリストル−マイヤーズ スクイブ カンパニー | カリウムチャネル抑制剤および方法 |
| 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 |
| JP4840594B2 (ja) * | 2004-03-23 | 2011-12-21 | 日産化学工業株式会社 | 抗不整脈薬としての３環性ベンゾピラン化合物 |
| 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 |
| US7902187B2 (en) | 2006-10-04 | 2011-03-08 | Wyeth Llc | 6-substituted 2-(benzimidazolyl)purine and purinone derivatives for immunosuppression |
| TW200831104A (en) | 2006-10-04 | 2008-08-01 | Pharmacopeia Inc | 6-substituted 2-(benzimidazolyl)purine and purinone derivatives for immunosuppression |
| TW200837064A (en) | 2006-10-04 | 2008-09-16 | Pharmacopeia Inc | 8-substituted 2-(benzimidazolyl)purine derivatives for immunosuppression |
| AR076524A1 (es) * | 2009-04-30 | 2011-06-15 | Nissan Chemical Ind Ltd | Forma cristalina de un compuesto de benzopirano triciclico y metodo de produccion de la misma |
| 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 |
| JP7822960B2 (ja) | 2020-05-06 | 2026-03-03 | バイエル、アクチエンゲゼルシャフト | 殺真菌性化合物としてのピリジン（チオ）アミド |
| CN115605462B (zh) | 2020-05-12 | 2026-04-14 | 拜耳公司 | 作为杀真菌化合物的三嗪和嘧啶(硫代)酰胺 |
| WO2021233861A1 (en) | 2020-05-19 | 2021-11-25 | Bayer Aktiengesellschaft | Azabicyclic(thio)amides as fungicidal compounds |
| CN115697059A (zh) | 2020-05-27 | 2023-02-03 | 拜耳公司 | 活性化合物组合 |
| US20250064060A1 (en) | 2021-11-03 | 2025-02-27 | 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 TW TW086106326A patent/TW496866B/zh not_active IP Right Cessation
- 1997-05-13 AR ARP970101998A patent/AR007115A1/es not_active Application Discontinuation
- 1997-05-13 AU AU20806/97A patent/AU711986B2/en not_active Ceased
- 1997-05-13 SK SK603-97A patent/SK283837B6/sk unknown
- 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 PT PT97107775T patent/PT807629E/pt unknown
- 1997-05-13 CN CNB971115400A patent/CN1204134C/zh not_active Expired - Fee Related
- 1997-05-13 ES ES97107775T patent/ES2218617T3/es not_active Expired - Lifetime
- 1997-05-13 DE DE59711352T patent/DE59711352D1/de not_active Expired - Lifetime
- 1997-05-13 DK DK97107775T patent/DK0807629T3/da active
- 1997-05-13 AT AT97107775T patent/ATE260909T1/de not_active IP Right Cessation
- 1997-05-13 EP EP97107775A patent/EP0807629B1/de not_active Expired - Lifetime
- 1997-05-13 NZ NZ314800A patent/NZ314800A/xx unknown
- 1997-05-14 BR BR9703161A patent/BR9703161A/pt not_active Application Discontinuation
- 1997-05-14 JP JP13798497A patent/JP4234798B2/ja not_active Expired - Fee Related
- 1997-05-14 CZ CZ971494A patent/CZ149497A3/cs unknown
- 1997-05-14 NO NO19972211A patent/NO315556B1/no unknown
- 1997-05-14 IL IL12082797A patent/IL120827A/en not_active IP Right Cessation
- 1997-05-15 HU HU9700903A patent/HUP9700903A3/hu unknown
- 1997-05-15 KR KR1019970018635A patent/KR100547921B1/ko not_active Expired - Fee Related
- 1997-05-15 CA CA002205477A patent/CA2205477A1/en not_active Abandoned
- 1997-05-15 PL PL319995A patent/PL191330B1/pl unknown
- 1997-11-26 AR ARP970105574A patent/AR010314A1/es unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PD00 | Pending as of 2000-06-30 in czech republic |