NO319563B1 - Sulfonamidsubstituerte kromaner, deres anvendelse som medikament samt farmasoytiske preparater inneholdende forbindelsene. - Google Patents

Sulfonamidsubstituerte kromaner, deres anvendelse som medikament samt farmasoytiske preparater inneholdende forbindelsene. Download PDF

Info

Publication number: NO319563B1
Authority: NO; Norway
Prior art keywords: methyl; phenyl; atoms; ethyl; means hydrogen
Prior art date: 1997-09-26

Application number

NO19984475A

Other languages

English (en)

Norwegian (no)

Other versions

NO984475D0 (no

NO984475L (no

Inventor

Klaus Weidmann

Uwe Gerlach

Joachim Brendel

Hans-Jochen Lang

Original Assignee

Aventis Pharma Gmbh

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1997-09-26

Filing date

1998-09-25

Publication date

2005-08-29

1998-09-25 Application filed by Aventis Pharma Gmbh filed Critical Aventis Pharma Gmbh

1998-09-25 Publication of NO984475D0 publication Critical patent/NO984475D0/no

1999-03-29 Publication of NO984475L publication Critical patent/NO984475L/no

2005-08-29 Publication of NO319563B1 publication Critical patent/NO319563B1/no

Links

150000001875 compounds Chemical class 0.000 title claims description 107
239000003814 drug Substances 0.000 title claims description 24
229940079593 drug Drugs 0.000 title claims description 9
239000000825 pharmaceutical preparation Substances 0.000 title claims description 7
-1 methoxy, dimethylamino, sulfamoyl Chemical group 0.000 claims description 172
239000001257 hydrogen Substances 0.000 claims description 127
229910052739 hydrogen Inorganic materials 0.000 claims description 127
125000004432 carbon atom Chemical group C* 0.000 claims description 97
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 93
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 83
125000000217 alkyl group Chemical group 0.000 claims description 68
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 67
229910052801 chlorine Inorganic materials 0.000 claims description 66
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 64
229910052731 fluorine Inorganic materials 0.000 claims description 63
150000002431 hydrogen Chemical class 0.000 claims description 62
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 57
229910052794 bromium Inorganic materials 0.000 claims description 54
150000003839 salts Chemical class 0.000 claims description 51
125000001424 substituent group Chemical group 0.000 claims description 46
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 44
108091006146 Channels Proteins 0.000 claims description 31
125000000623 heterocyclic group Chemical group 0.000 claims description 28
239000000126 substance Substances 0.000 claims description 27
229910052740 iodine Inorganic materials 0.000 claims description 23
238000011321 prophylaxis Methods 0.000 claims description 21
125000000753 cycloalkyl group Chemical group 0.000 claims description 20
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 19
125000005004 perfluoroethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 17
238000011282 treatment Methods 0.000 claims description 17
238000002360 preparation method Methods 0.000 claims description 16
239000013543 active substance Substances 0.000 claims description 14
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 14
125000005009 perfluoropropyl group Chemical group FC(C(C(F)(F)F)(F)F)(F)* 0.000 claims description 14
125000002883 imidazolyl group Chemical group 0.000 claims description 13
125000004076 pyridyl group Chemical group 0.000 claims description 13
125000002947 alkylene group Chemical group 0.000 claims description 11
238000002560 therapeutic procedure Methods 0.000 claims description 11
230000009471 action Effects 0.000 claims description 10
206010003119 arrhythmia Diseases 0.000 claims description 10
230000006793 arrhythmia Effects 0.000 claims description 8
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
238000004519 manufacturing process Methods 0.000 claims description 7
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 6
201000010099 disease Diseases 0.000 claims description 6
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 6
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 6
125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 5
230000002401 inhibitory effect Effects 0.000 claims description 5
125000005493 quinolyl group Chemical group 0.000 claims description 5
206010003658 Atrial Fibrillation Diseases 0.000 claims description 4
206010003662 Atrial flutter Diseases 0.000 claims description 4
206010012735 Diarrhoea Diseases 0.000 claims description 4
206010019280 Heart failures Diseases 0.000 claims description 4
208000025865 Ulcer Diseases 0.000 claims description 4
230000036982 action potential Effects 0.000 claims description 4
230000027119 gastric acid secretion Effects 0.000 claims description 4
125000005956 isoquinolyl group Chemical group 0.000 claims description 4
230000000144 pharmacologic effect Effects 0.000 claims description 4
125000001544 thienyl group Chemical group 0.000 claims description 4
231100000397 ulcer Toxicity 0.000 claims description 4
206010003130 Arrhythmia supraventricular Diseases 0.000 claims description 3
206010049418 Sudden Cardiac Death Diseases 0.000 claims description 3
206010042600 Supraventricular arrhythmias Diseases 0.000 claims description 3
206010047281 Ventricular arrhythmia Diseases 0.000 claims description 3
230000001746 atrial effect Effects 0.000 claims description 3
208000021302 gastroesophageal reflux disease Diseases 0.000 claims description 3
230000000968 intestinal effect Effects 0.000 claims description 3
230000001404 mediated effect Effects 0.000 claims description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
230000033764 rhythmic process Effects 0.000 claims description 3
210000002784 stomach Anatomy 0.000 claims description 3
230000002861 ventricular Effects 0.000 claims description 3
239000000654 additive Substances 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
208000003663 ventricular fibrillation Diseases 0.000 claims description 2
208000010496 Heart Arrest Diseases 0.000 claims 1
230000000996 additive effect Effects 0.000 claims 1
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 88
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 62
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 54
239000000243 solution Substances 0.000 description 50
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 45
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 44
238000000034 method Methods 0.000 description 39
239000000460 chlorine Substances 0.000 description 37
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 32
238000006243 chemical reaction Methods 0.000 description 29
239000000047 product Substances 0.000 description 27
229910000104 sodium hydride Inorganic materials 0.000 description 24
239000002904 solvent Substances 0.000 description 22
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
238000003756 stirring Methods 0.000 description 21
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 20
238000001704 evaporation Methods 0.000 description 20
230000008020 evaporation Effects 0.000 description 20
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 19
239000003921 oil Substances 0.000 description 19
235000019198 oils Nutrition 0.000 description 19
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
238000001035 drying Methods 0.000 description 18
239000000741 silica gel Substances 0.000 description 18
229910002027 silica gel Inorganic materials 0.000 description 18
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 17
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 17
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
239000012074 organic phase Substances 0.000 description 15
229940124530 sulfonamide Drugs 0.000 description 15
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 description 14
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
239000002585 base Substances 0.000 description 14
239000000203 mixture Substances 0.000 description 14
239000002253 acid Substances 0.000 description 13
238000002425 crystallisation Methods 0.000 description 13
230000008025 crystallization Effects 0.000 description 13
150000003456 sulfonamides Chemical class 0.000 description 13
150000001412 amines Chemical class 0.000 description 12
235000011121 sodium hydroxide Nutrition 0.000 description 12
238000004587 chromatography analysis Methods 0.000 description 11
230000000694 effects Effects 0.000 description 11
239000007787 solid Substances 0.000 description 11
239000004698 Polyethylene Substances 0.000 description 10
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
239000011541 reaction mixture Substances 0.000 description 10
238000010992 reflux Methods 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 9
238000001816 cooling Methods 0.000 description 9
239000012312 sodium hydride Substances 0.000 description 9
239000000725 suspension Substances 0.000 description 9
KBYNVRQDBSJLFV-UHFFFAOYSA-N 5-[methylsulfonyl-(2,2,6-trimethyl-3,4-dihydrochromen-4-yl)amino]pentanoic acid Chemical compound O1C(C)(C)CC(N(CCCCC(O)=O)S(C)(=O)=O)C2=CC(C)=CC=C21 KBYNVRQDBSJLFV-UHFFFAOYSA-N 0.000 description 8
UAXWPLCLDSMHRF-UHFFFAOYSA-N 6-hydroxy-2,2-dimethyl-3h-chromen-4-one Chemical compound OC1=CC=C2OC(C)(C)CC(=O)C2=C1 UAXWPLCLDSMHRF-UHFFFAOYSA-N 0.000 description 8
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 8
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 8
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
230000000903 blocking effect Effects 0.000 description 8
239000012043 crude product Substances 0.000 description 8
229910052943 magnesium sulfate Inorganic materials 0.000 description 8
235000019341 magnesium sulphate Nutrition 0.000 description 8
238000002844 melting Methods 0.000 description 8
230000008018 melting Effects 0.000 description 8
229910052757 nitrogen Inorganic materials 0.000 description 8
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
238000010626 work up procedure Methods 0.000 description 8
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 7
PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 7
210000000287 oocyte Anatomy 0.000 description 7
LZZKHFZZQSLELN-UHFFFAOYSA-N 2-[ethylsulfonyl-(6-fluoro-2,2-dimethyl-3,4-dihydrochromen-4-yl)amino]acetyl chloride Chemical compound C1=C(F)C=C2C(N(CC(Cl)=O)S(=O)(=O)CC)CC(C)(C)OC2=C1 LZZKHFZZQSLELN-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
239000000546 pharmaceutical excipient Substances 0.000 description 6
ZLBOCPFJUSXNCR-UHFFFAOYSA-N 2-[ethylsulfonyl-(6-fluoro-2,2-dimethyl-3,4-dihydrochromen-4-yl)amino]acetic acid Chemical compound C1=C(F)C=C2C(N(CC(O)=O)S(=O)(=O)CC)CC(C)(C)OC2=C1 ZLBOCPFJUSXNCR-UHFFFAOYSA-N 0.000 description 5
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 5
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 5
241000282414 Homo sapiens Species 0.000 description 5
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 5
150000001298 alcohols Chemical class 0.000 description 5
238000005804 alkylation reaction Methods 0.000 description 5
239000003416 antiarrhythmic agent Substances 0.000 description 5
239000000969 carrier Substances 0.000 description 5
238000010438 heat treatment Methods 0.000 description 5
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 5
MNJSYFPCVBZDGI-UHFFFAOYSA-N n-(2,2-dimethyl-6-phenylmethoxy-3,4-dihydrochromen-4-yl)methanesulfonamide Chemical compound C=1C=C2OC(C)(C)CC(NS(C)(=O)=O)C2=CC=1OCC1=CC=CC=C1 MNJSYFPCVBZDGI-UHFFFAOYSA-N 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
238000000746 purification Methods 0.000 description 5
WADSJYLPJPTMLN-UHFFFAOYSA-N 3-(cycloundecen-1-yl)-1,2-diazacycloundec-2-ene Chemical compound C1CCCCCCCCC=C1C1=NNCCCCCCCC1 WADSJYLPJPTMLN-UHFFFAOYSA-N 0.000 description 4
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 4
241000700199 Cavia porcellus Species 0.000 description 4
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
230000002378 acidificating effect Effects 0.000 description 4
239000008186 active pharmaceutical agent Substances 0.000 description 4
239000002168 alkylating agent Substances 0.000 description 4
229940100198 alkylating agent Drugs 0.000 description 4
230000003288 anthiarrhythmic effect Effects 0.000 description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
230000037396 body weight Effects 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
210000001072 colon Anatomy 0.000 description 4
239000006185 dispersion Substances 0.000 description 4
238000003379 elimination reaction Methods 0.000 description 4
150000002148 esters Chemical class 0.000 description 4
239000003112 inhibitor Substances 0.000 description 4
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 4
239000001301 oxygen Substances 0.000 description 4
229910052760 oxygen Inorganic materials 0.000 description 4
FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 4
239000003208 petroleum Substances 0.000 description 4
239000012071 phase Substances 0.000 description 4
125000006239 protecting group Chemical group 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
238000006722 reduction reaction Methods 0.000 description 4
230000002829 reductive effect Effects 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 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
YNPDFBFVMJNGKZ-UHFFFAOYSA-N 2'-Hydroxy-5'-methylacetophenone Chemical compound CC(=O)C1=CC(C)=CC=C1O YNPDFBFVMJNGKZ-UHFFFAOYSA-N 0.000 description 3
XPQIPUZPSLAZDV-UHFFFAOYSA-N 2-pyridylethylamine Chemical compound NCCC1=CC=CC=N1 XPQIPUZPSLAZDV-UHFFFAOYSA-N 0.000 description 3
JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 3
SEBPXHSZHLFWRL-UHFFFAOYSA-N 3,4-dihydro-2,2,5,7,8-pentamethyl-2h-1-benzopyran-6-ol Chemical compound O1C(C)(C)CCC2=C1C(C)=C(C)C(O)=C2C SEBPXHSZHLFWRL-UHFFFAOYSA-N 0.000 description 3
CKFJGMBEWVJFAD-UHFFFAOYSA-N 5-[ethylsulfonyl-(2,2,6-trimethyl-3,4-dihydrochromen-4-yl)amino]pentanoic acid Chemical compound C1=C(C)C=C2C(N(CCCCC(O)=O)S(=O)(=O)CC)CC(C)(C)OC2=C1 CKFJGMBEWVJFAD-UHFFFAOYSA-N 0.000 description 3
GBKKQIPASWYIGM-UHFFFAOYSA-N 6-butoxy-2,2-dimethyl-3,4-dihydrochromen-4-amine Chemical compound O1C(C)(C)CC(N)C2=CC(OCCCC)=CC=C21 GBKKQIPASWYIGM-UHFFFAOYSA-N 0.000 description 3
UEIJOFFCTBAQGZ-UHFFFAOYSA-N 6-butoxy-2,2-dimethyl-3h-chromen-4-one Chemical compound O1C(C)(C)CC(=O)C2=CC(OCCCC)=CC=C21 UEIJOFFCTBAQGZ-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 3
239000005695 Ammonium acetate Substances 0.000 description 3
208000024172 Cardiovascular disease Diseases 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
239000007868 Raney catalyst Substances 0.000 description 3
229910000564 Raney nickel Inorganic materials 0.000 description 3
241000269370 Xenopus <genus> Species 0.000 description 3
230000004913 activation Effects 0.000 description 3
125000004442 acylamino group Chemical group 0.000 description 3
150000001336 alkenes Chemical class 0.000 description 3
238000007112 amidation reaction Methods 0.000 description 3
229910021529 ammonia Inorganic materials 0.000 description 3
229940043376 ammonium acetate Drugs 0.000 description 3
235000019257 ammonium acetate Nutrition 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
230000009286 beneficial effect Effects 0.000 description 3
229910052799 carbon Inorganic materials 0.000 description 3
150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
150000001735 carboxylic acids Chemical class 0.000 description 3
210000004413 cardiac myocyte Anatomy 0.000 description 3
238000009903 catalytic hydrogenation reaction Methods 0.000 description 3
230000005595 deprotonation Effects 0.000 description 3
238000010537 deprotonation reaction Methods 0.000 description 3
230000008030 elimination Effects 0.000 description 3
239000003995 emulsifying agent Substances 0.000 description 3
150000002118 epoxides Chemical class 0.000 description 3
125000004494 ethyl ester group Chemical group 0.000 description 3
239000000284 extract Substances 0.000 description 3
239000000706 filtrate Substances 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
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
238000011065 in-situ storage Methods 0.000 description 3
238000001802 infusion Methods 0.000 description 3
150000002576 ketones Chemical class 0.000 description 3
239000012280 lithium aluminium hydride Substances 0.000 description 3
YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 3
MGCAHKRDQDNZQF-UHFFFAOYSA-N methyl 5-[ethylsulfonyl-(2,2,6-trimethyl-3,4-dihydrochromen-4-yl)amino]pentanoate Chemical compound C1=C(C)C=C2C(N(CCCCC(=O)OC)S(=O)(=O)CC)CC(C)(C)OC2=C1 MGCAHKRDQDNZQF-UHFFFAOYSA-N 0.000 description 3
AJNCNWVNDWDIFM-UHFFFAOYSA-N n-(6-butoxy-2,2-dimethyl-3,4-dihydrochromen-4-yl)methanesulfonamide Chemical compound O1C(C)(C)CC(NS(C)(=O)=O)C2=CC(OCCCC)=CC=C21 AJNCNWVNDWDIFM-UHFFFAOYSA-N 0.000 description 3
239000012299 nitrogen atmosphere Substances 0.000 description 3
125000004433 nitrogen atom Chemical group N* 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
235000011181 potassium carbonates Nutrition 0.000 description 3
238000001556 precipitation Methods 0.000 description 3
238000007127 saponification reaction Methods 0.000 description 3
210000002460 smooth muscle Anatomy 0.000 description 3
239000011734 sodium Substances 0.000 description 3
238000006467 substitution reaction Methods 0.000 description 3
230000001225 therapeutic effect Effects 0.000 description 3
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 2
DXZVRFYHBJOICQ-UHFFFAOYSA-N 2,2,6-trimethyl-3,4-dihydrochromen-4-amine Chemical compound O1C(C)(C)CC(N)C2=CC(C)=CC=C21 DXZVRFYHBJOICQ-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
VIDJEZKJMHVLML-UHFFFAOYSA-N 2,2-diethyl-6-methyl-3,4-dihydrochromen-4-amine Chemical compound CC1=CC=C2OC(CC)(CC)CC(N)C2=C1 VIDJEZKJMHVLML-UHFFFAOYSA-N 0.000 description 2
XKVCHUUABJATKE-UHFFFAOYSA-N 2,2-diethyl-6-methyl-3h-chromen-4-one Chemical compound CC1=CC=C2OC(CC)(CC)CC(=O)C2=C1 XKVCHUUABJATKE-UHFFFAOYSA-N 0.000 description 2
APPZTNAPKBNODA-UHFFFAOYSA-N 2,2-dimethyl-6-phenylmethoxy-3,4-dihydrochromen-4-amine Chemical compound C=1C=C2OC(C)(C)CC(N)C2=CC=1OCC1=CC=CC=C1 APPZTNAPKBNODA-UHFFFAOYSA-N 0.000 description 2
MYUGVLBDIQAJOG-UHFFFAOYSA-N 2-[(6-butoxy-2,2-dimethyl-3,4-dihydrochromen-4-yl)-methylsulfonylamino]-n-(diaminomethylidene)acetamide Chemical compound O1C(C)(C)CC(N(CC(=O)N=C(N)N)S(C)(=O)=O)C2=CC(OCCCC)=CC=C21 MYUGVLBDIQAJOG-UHFFFAOYSA-N 0.000 description 2
IPUPNKKOTLQLQG-UHFFFAOYSA-N 2-[(6-chloro-3-hydroxy-2,2-dimethyl-3,4-dihydrochromen-4-yl)methylsulfonylamino]acetic acid Chemical compound C1=C(Cl)C=C2C(CS(=O)(=O)NCC(O)=O)C(O)C(C)(C)OC2=C1 IPUPNKKOTLQLQG-UHFFFAOYSA-N 0.000 description 2
WOUANPHGFPAJCA-UHFFFAOYSA-N 2-[benzyl(methyl)amino]ethanol Chemical compound OCCN(C)CC1=CC=CC=C1 WOUANPHGFPAJCA-UHFFFAOYSA-N 0.000 description 2
HBLDKCGIBIGVPC-UHFFFAOYSA-N 3,4-dihydro-2h-chromen-3-ol Chemical compound C1=CC=C2CC(O)COC2=C1 HBLDKCGIBIGVPC-UHFFFAOYSA-N 0.000 description 2
JMLHQRQZCMCQNJ-UHFFFAOYSA-N 4-(methylamino)butanoic acid;hydrochloride Chemical compound Cl.CNCCCC(O)=O JMLHQRQZCMCQNJ-UHFFFAOYSA-N 0.000 description 2
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 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical compound C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
RBCQIGDLDJXPRT-UHFFFAOYSA-N C(C)OC(COCCN(S(=O)(=O)C)C1CC(OC2=CC=C(C=C12)OCCCC)(C)C)=O Chemical compound C(C)OC(COCCN(S(=O)(=O)C)C1CC(OC2=CC=C(C=C12)OCCCC)(C)C)=O RBCQIGDLDJXPRT-UHFFFAOYSA-N 0.000 description 2
206010007559 Cardiac failure congestive Diseases 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
101100379080 Emericella variicolor andB gene Proteins 0.000 description 2
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 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 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
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
239000012359 Methanesulfonyl chloride Substances 0.000 description 2
CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 2
241000283973 Oryctolagus cuniculus Species 0.000 description 2
229910019142 PO4 Inorganic materials 0.000 description 2
BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
102000004257 Potassium Channel Human genes 0.000 description 2
239000002262 Schiff base Substances 0.000 description 2
150000004753 Schiff bases Chemical class 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
230000003213 activating effect Effects 0.000 description 2
230000001476 alcoholic effect Effects 0.000 description 2
230000029936 alkylation Effects 0.000 description 2
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
230000009435 amidation Effects 0.000 description 2
125000003277 amino group Chemical group 0.000 description 2
235000011114 ammonium hydroxide Nutrition 0.000 description 2
125000003118 aryl group Chemical group 0.000 description 2
230000008901 benefit Effects 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
230000036772 blood pressure Effects 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 2
239000011575 calcium Substances 0.000 description 2
229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 2
210000004027 cell Anatomy 0.000 description 2
239000003638 chemical reducing agent Substances 0.000 description 2
150000001805 chlorine compounds Chemical class 0.000 description 2
150000008371 chromenes Chemical class 0.000 description 2
229940082627 class iii antiarrhythmics Drugs 0.000 description 2
238000006482 condensation reaction Methods 0.000 description 2
230000003111 delayed effect Effects 0.000 description 2
238000011161 development Methods 0.000 description 2
SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 2
239000002270 dispersing agent Substances 0.000 description 2
238000004821 distillation Methods 0.000 description 2
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 2
229960002994 dofetilide Drugs 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
230000032050 esterification Effects 0.000 description 2
238000005886 esterification reaction Methods 0.000 description 2
FRYHCSODNHYDPU-UHFFFAOYSA-N ethanesulfonyl chloride Chemical compound CCS(Cl)(=O)=O FRYHCSODNHYDPU-UHFFFAOYSA-N 0.000 description 2
150000002170 ethers Chemical class 0.000 description 2
DLNYWVRHQUKKMS-UHFFFAOYSA-N ethyl 2-[ethylsulfonyl-(6-fluoro-2,2-dimethyl-3,4-dihydrochromen-4-yl)amino]acetate Chemical compound C1=C(F)C=C2C(N(CC(=O)OCC)S(=O)(=O)CC)CC(C)(C)OC2=C1 DLNYWVRHQUKKMS-UHFFFAOYSA-N 0.000 description 2
XBPOBCXHALHJFP-UHFFFAOYSA-N ethyl 4-bromobutanoate Chemical compound CCOC(=O)CCCBr XBPOBCXHALHJFP-UHFFFAOYSA-N 0.000 description 2
238000001914 filtration Methods 0.000 description 2
239000006260 foam Substances 0.000 description 2
239000008103 glucose Substances 0.000 description 2
235000001727 glucose Nutrition 0.000 description 2
150000007857 hydrazones Chemical class 0.000 description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
239000003999 initiator Substances 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
229910052744 lithium Inorganic materials 0.000 description 2
230000007246 mechanism Effects 0.000 description 2
229910052751 metal Inorganic materials 0.000 description 2
239000002184 metal Substances 0.000 description 2
IZHCNTFNBHWITE-UHFFFAOYSA-N methyl 2-[(2,2-diethyl-6-methyl-3,4-dihydrochromen-4-yl)-ethylsulfonylamino]acetate Chemical compound CC1=CC=C2OC(CC)(CC)CC(N(CC(=O)OC)S(=O)(=O)CC)C2=C1 IZHCNTFNBHWITE-UHFFFAOYSA-N 0.000 description 2
XKRBFPINBXJZBZ-UHFFFAOYSA-N methyl 2-[(6-chloro-3-hydroxy-2,2-dimethyl-3,4-dihydrochromen-4-yl)-methylsulfonylamino]acetate Chemical compound C1=C(Cl)C=C2C(N(CC(=O)OC)S(C)(=O)=O)C(O)C(C)(C)OC2=C1 XKRBFPINBXJZBZ-UHFFFAOYSA-N 0.000 description 2
210000004165 myocardium Anatomy 0.000 description 2
ACDCRJGJMQYKHT-UHFFFAOYSA-N n-(2,2-dimethyl-6-phenylmethoxy-3,4-dihydrochromen-4-yl)-n-(4-hydroxybutyl)methanesulfonamide Chemical compound C=1C=C2OC(C)(C)CC(N(CCCCO)S(C)(=O)=O)C2=CC=1OCC1=CC=CC=C1 ACDCRJGJMQYKHT-UHFFFAOYSA-N 0.000 description 2
UCGHCNZIASFQAF-UHFFFAOYSA-N n-(6-butoxy-2,2-dimethyl-3h-chromen-4-ylidene)hydroxylamine Chemical compound O1C(C)(C)CC(=NO)C2=CC(OCCCC)=CC=C21 UCGHCNZIASFQAF-UHFFFAOYSA-N 0.000 description 2
RWIVICVCHVMHMU-UHFFFAOYSA-N n-aminoethylmorpholine Chemical compound NCCN1CCOCC1 RWIVICVCHVMHMU-UHFFFAOYSA-N 0.000 description 2
SASNBVQSOZSTPD-UHFFFAOYSA-N n-methylphenethylamine Chemical compound CNCCC1=CC=CC=C1 SASNBVQSOZSTPD-UHFFFAOYSA-N 0.000 description 2
JMANVNJQNLATNU-UHFFFAOYSA-N oxalonitrile Chemical compound N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 2
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
150000002923 oximes Chemical class 0.000 description 2
235000021317 phosphate Nutrition 0.000 description 2
239000002571 phosphodiesterase inhibitor Substances 0.000 description 2
239000002798 polar solvent Substances 0.000 description 2
229940072033 potash Drugs 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
239000011591 potassium Substances 0.000 description 2
235000015320 potassium carbonate Nutrition 0.000 description 2
108020001213 potassium channel Proteins 0.000 description 2
102000004169 proteins and genes Human genes 0.000 description 2
108090000623 proteins and genes Proteins 0.000 description 2
125000003373 pyrazinyl group Chemical group 0.000 description 2
150000003254 radicals Chemical group 0.000 description 2
239000011347 resin Substances 0.000 description 2
229920005989 resin Polymers 0.000 description 2
239000012262 resinous product Substances 0.000 description 2
238000007363 ring formation reaction Methods 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
229910000029 sodium carbonate Inorganic materials 0.000 description 2
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
239000003381 stabilizer Substances 0.000 description 2
235000000346 sugar Nutrition 0.000 description 2
125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 2
208000024891 symptom Diseases 0.000 description 2
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
210000001519 tissue Anatomy 0.000 description 2
125000004665 trialkylsilyl group Chemical group 0.000 description 2
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 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
239000000052 vinegar Substances 0.000 description 2
235000021419 vinegar Nutrition 0.000 description 2
125000004509 1,3,4-oxadiazol-2-yl group Chemical group O1C(=NN=C1)* 0.000 description 1
125000004510 1,3,4-oxadiazol-5-yl group Chemical group O1C=NN=C1* 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
RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
IAADPEJYEZPFOT-UHFFFAOYSA-N 1-(1h-imidazol-2-yl)propan-1-amine Chemical compound CCC(N)C1=NC=CN1 IAADPEJYEZPFOT-UHFFFAOYSA-N 0.000 description 1
KOFFXZYMDLWRHX-UHFFFAOYSA-N 1-(5-fluoro-2-hydroxyphenyl)ethanone Chemical compound CC(=O)C1=CC(F)=CC=C1O KOFFXZYMDLWRHX-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
125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
UCOSRTUSVXHIMK-UHFFFAOYSA-N 1h-benzimidazol-2-ylmethanamine Chemical compound C1=CC=C2NC(CN)=NC2=C1 UCOSRTUSVXHIMK-UHFFFAOYSA-N 0.000 description 1
WLDWSGZHNBANIO-UHFFFAOYSA-N 2',5'-Dihydroxyacetophenone Chemical compound CC(=O)C1=CC(O)=CC=C1O WLDWSGZHNBANIO-UHFFFAOYSA-N 0.000 description 1
XWROIWDXQLSBBR-UHFFFAOYSA-N 2,2-dimethyl-6-phenylmethoxy-3h-chromen-4-one Chemical compound C=1C=C2OC(C)(C)CC(=O)C2=CC=1OCC1=CC=CC=C1 XWROIWDXQLSBBR-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
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 1
WOXFMYVTSLAQMO-UHFFFAOYSA-N 2-Pyridinemethanamine Chemical compound NCC1=CC=CC=N1 WOXFMYVTSLAQMO-UHFFFAOYSA-N 0.000 description 1
AGUJNBVNVZQPQI-UHFFFAOYSA-N 2-[(2,2-dimethyl-6-phenylmethoxy-3,4-dihydrochromen-4-yl)-methylsulfonylamino]-n-(2-pyridin-2-ylethyl)acetamide Chemical compound C12=CC(OCC=3C=CC=CC=3)=CC=C2OC(C)(C)CC1N(S(C)(=O)=O)CC(=O)NCCC1=CC=CC=N1 AGUJNBVNVZQPQI-UHFFFAOYSA-N 0.000 description 1
TUISUBHEENBZFL-UHFFFAOYSA-N 2-[(2,2-dimethyl-6-phenylmethoxy-3,4-dihydrochromen-4-yl)methylsulfonylamino]acetic acid Chemical compound C=1C=C2OC(C)(C)CC(CS(=O)(=O)NCC(O)=O)C2=CC=1OCC1=CC=CC=C1 TUISUBHEENBZFL-UHFFFAOYSA-N 0.000 description 1
XXPQMUTVULPZRB-UHFFFAOYSA-N 2-[(6-chloro-3-hydroxy-2,2-dimethyl-3,4-dihydrochromen-4-yl)-methylsulfonylamino]-n,n-dimethylacetamide Chemical compound C1=C(Cl)C=C2C(N(CC(=O)N(C)C)S(C)(=O)=O)C(O)C(C)(C)OC2=C1 XXPQMUTVULPZRB-UHFFFAOYSA-N 0.000 description 1
KBWPSEZPXBTYTC-UHFFFAOYSA-N 2-[(6-chloro-3-hydroxy-2,2-dimethyl-3,4-dihydrochromen-4-yl)methylsulfonylamino]-n-(2-phenylethyl)acetamide Chemical compound OC1C(C)(C)OC2=CC=C(Cl)C=C2C1CS(=O)(=O)NCC(=O)NCCC1=CC=CC=C1 KBWPSEZPXBTYTC-UHFFFAOYSA-N 0.000 description 1
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
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 1
GHKJRJJKOHIHDJ-UHFFFAOYSA-N 2-[ethylsulfonyl-(6-fluoro-2,2-dimethyl-3,4-dihydrochromen-4-yl)amino]-n-(1,2-thiazol-5-yl)acetamide Chemical compound C1C(C)(C)OC2=CC=C(F)C=C2C1N(S(=O)(=O)CC)CC(=O)NC1=CC=NS1 GHKJRJJKOHIHDJ-UHFFFAOYSA-N 0.000 description 1
PDKZSRXWDOXJFX-UHFFFAOYSA-N 2-[ethylsulfonyl-(6-fluoro-2,2-dimethyl-3,4-dihydrochromen-4-yl)amino]-n-(1-methylbenzimidazol-2-yl)acetamide Chemical compound C1C(C)(C)OC2=CC=C(F)C=C2C1N(S(=O)(=O)CC)CC(=O)NC1=NC2=CC=CC=C2N1C PDKZSRXWDOXJFX-UHFFFAOYSA-N 0.000 description 1
KYGSIUINOBKLMA-UHFFFAOYSA-N 2-[ethylsulfonyl-(6-fluoro-2,2-dimethyl-3,4-dihydrochromen-4-yl)amino]-n-(2-morpholin-4-ylethyl)acetamide Chemical compound C1C(C)(C)OC2=CC=C(F)C=C2C1N(S(=O)(=O)CC)CC(=O)NCCN1CCOCC1 KYGSIUINOBKLMA-UHFFFAOYSA-N 0.000 description 1
TVILXSMRQDORHA-UHFFFAOYSA-N 2-[ethylsulfonyl-(6-fluoro-2,2-dimethyl-3,4-dihydrochromen-4-yl)amino]-n-(3-imidazol-1-ylpropyl)acetamide Chemical compound C1C(C)(C)OC2=CC=C(F)C=C2C1N(S(=O)(=O)CC)CC(=O)NCCCN1C=CN=C1 TVILXSMRQDORHA-UHFFFAOYSA-N 0.000 description 1
PIPNWVSNJHADIZ-UHFFFAOYSA-N 2-[ethylsulfonyl-(6-fluoro-2,2-dimethyl-3,4-dihydrochromen-4-yl)amino]-n-(5-methyl-1,2-oxazol-3-yl)acetamide Chemical compound C1C(C)(C)OC2=CC=C(F)C=C2C1N(S(=O)(=O)CC)CC(=O)NC=1C=C(C)ON=1 PIPNWVSNJHADIZ-UHFFFAOYSA-N 0.000 description 1
LLHWYJULMPRCDH-UHFFFAOYSA-N 2-[ethylsulfonyl-(6-fluoro-2,2-dimethyl-3,4-dihydrochromen-4-yl)amino]-n-pyridin-3-ylacetamide Chemical compound C1C(C)(C)OC2=CC=C(F)C=C2C1N(S(=O)(=O)CC)CC(=O)NC1=CC=CN=C1 LLHWYJULMPRCDH-UHFFFAOYSA-N 0.000 description 1
JUIKUQOUMZUFQT-UHFFFAOYSA-N 2-bromoacetamide Chemical compound NC(=O)CBr JUIKUQOUMZUFQT-UHFFFAOYSA-N 0.000 description 1
AUHYZQCEIVEMFH-UHFFFAOYSA-N 2-bromopropanamide Chemical compound CC(Br)C(N)=O AUHYZQCEIVEMFH-UHFFFAOYSA-N 0.000 description 1
FSJOLBAFVKSQQJ-UHFFFAOYSA-N 2-ethylpyrazol-3-amine Chemical compound CCN1N=CC=C1N FSJOLBAFVKSQQJ-UHFFFAOYSA-N 0.000 description 1
CJNRGSHEMCMUOE-UHFFFAOYSA-N 2-piperidin-1-ylethanamine Chemical compound NCCN1CCCCC1 CJNRGSHEMCMUOE-UHFFFAOYSA-N 0.000 description 1
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
KVZQPAQBIFDZPX-UHFFFAOYSA-N 3,4-dihydro-2h-chromene-2,3-diol Chemical class C1=CC=C2OC(O)C(O)CC2=C1 KVZQPAQBIFDZPX-UHFFFAOYSA-N 0.000 description 1
SDIWTVFNNJGQAD-UHFFFAOYSA-N 3-[ethylsulfonyl-(6-fluoro-2,2-dimethyl-3,4-dihydrochromen-4-yl)amino]propanamide Chemical compound C1=C(F)C=C2C(N(CCC(N)=O)S(=O)(=O)CC)CC(C)(C)OC2=C1 SDIWTVFNNJGQAD-UHFFFAOYSA-N 0.000 description 1
PSUXTZLDBVEZTD-UHFFFAOYSA-N 3-bromopropoxymethylbenzene Chemical compound BrCCCOCC1=CC=CC=C1 PSUXTZLDBVEZTD-UHFFFAOYSA-N 0.000 description 1
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
MNUGSTYRJFTKIA-UHFFFAOYSA-N 4-[ethylsulfonyl-(6-fluoro-2,2-dimethyl-3,4-dihydrochromen-4-yl)amino]butanoic acid Chemical compound C1=C(F)C=C2C(N(CCCC(O)=O)S(=O)(=O)CC)CC(C)(C)OC2=C1 MNUGSTYRJFTKIA-UHFFFAOYSA-N 0.000 description 1
NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 1
SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 description 1
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical compound [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
GKCIZOOMWMXYIF-UHFFFAOYSA-N 5-(2-aminoethyl)-2-methoxybenzenesulfonamide;hydrochloride Chemical compound Cl.COC1=CC=C(CCN)C=C1S(N)(=O)=O GKCIZOOMWMXYIF-UHFFFAOYSA-N 0.000 description 1
MDQBBBHQHLVRCT-UHFFFAOYSA-N 5-[ethylsulfonyl-(2,2,6-trimethyl-3,4-dihydrochromen-4-yl)amino]-n-(3-imidazol-1-ylpropyl)pentanamide Chemical compound C1C(C)(C)OC2=CC=C(C)C=C2C1N(S(=O)(=O)CC)CCCCC(=O)NCCCN1C=CN=C1 MDQBBBHQHLVRCT-UHFFFAOYSA-N 0.000 description 1
UHHSZJVGPWLHSN-UHFFFAOYSA-N 5-[methylsulfonyl-(2,2,6-trimethyl-3,4-dihydrochromen-4-yl)amino]-n-(pyridin-2-ylmethyl)pentanamide Chemical compound C12=CC(C)=CC=C2OC(C)(C)CC1N(S(C)(=O)=O)CCCCC(=O)NCC1=CC=CC=N1 UHHSZJVGPWLHSN-UHFFFAOYSA-N 0.000 description 1
125000004539 5-benzimidazolyl group Chemical group N1=CNC2=C1C=CC(=C2)* 0.000 description 1
FKPXGNGUVSHWQQ-UHFFFAOYSA-N 5-methyl-1,2-oxazol-3-amine Chemical compound CC1=CC(N)=NO1 FKPXGNGUVSHWQQ-UHFFFAOYSA-N 0.000 description 1
CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
NDIVLDNITQYABM-UHFFFAOYSA-N 6-chloro-2,2-dimethyl-1a,7b-dihydrooxireno[2,3-c]chromene Chemical compound CC1(C)OC2=CC=C(Cl)C=C2C2C1O2 NDIVLDNITQYABM-UHFFFAOYSA-N 0.000 description 1
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 1
ZHFGVQJTRUBVBR-UHFFFAOYSA-N 6-fluoro-2,2-dimethyl-3h-chromen-4-one;pyrrolidine Chemical compound C1CCNC1.FC1=CC=C2OC(C)(C)CC(=O)C2=C1 ZHFGVQJTRUBVBR-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
239000005541 ACE inhibitor Substances 0.000 description 1
KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 1
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
229940123073 Angiotensin antagonist Drugs 0.000 description 1
MREBEPTUUMTTIA-PCLIKHOPSA-N Azimilide Chemical compound C1CN(C)CCN1CCCCN1C(=O)N(\N=C\C=2OC(=CC=2)C=2C=CC(Cl)=CC=2)CC1=O MREBEPTUUMTTIA-PCLIKHOPSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
NZLXHOSLLZGHDH-UHFFFAOYSA-N C1C(C)(C)OC2=CC=C(F)C=C2C1N(S(=O)(=O)CC)CC(=O)OCCN(C)CC1=CC=CC=C1 Chemical compound C1C(C)(C)OC2=CC=C(F)C=C2C1N(S(=O)(=O)CC)CC(=O)OCCN(C)CC1=CC=CC=C1 NZLXHOSLLZGHDH-UHFFFAOYSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
229940127291 Calcium channel antagonist Drugs 0.000 description 1
239000004215 Carbon black (E152) Substances 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
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
XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
108010061435 Enalapril Proteins 0.000 description 1
244000165918 Eucalyptus papuana Species 0.000 description 1
KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
238000005863 Friedel-Crafts acylation reaction Methods 0.000 description 1
238000005727 Friedel-Crafts reaction Methods 0.000 description 1
208000018522 Gastrointestinal disease Diseases 0.000 description 1
241001608331 Gonyaulax digitale Species 0.000 description 1
229920000084 Gum arabic Polymers 0.000 description 1
239000007995 HEPES buffer Substances 0.000 description 1
229940122957 Histamine H2 receptor antagonist Drugs 0.000 description 1
241000282412 Homo Species 0.000 description 1
206010021118 Hypotonia Diseases 0.000 description 1
206010022998 Irritability Diseases 0.000 description 1
239000002841 Lewis acid Substances 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 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
241000276498 Pollachius virens Species 0.000 description 1
229940127315 Potassium Channel Openers Drugs 0.000 description 1
241000700159 Rattus Species 0.000 description 1
238000000297 Sandmeyer reaction Methods 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
235000019486 Sunflower oil Nutrition 0.000 description 1
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
208000018452 Torsade de pointes Diseases 0.000 description 1
208000002363 Torsades de Pointes Diseases 0.000 description 1
241000269368 Xenopus laevis Species 0.000 description 1
FPQVGDGSRVMNMR-JCTPKUEWSA-N [[(z)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-(dimethylamino)methylidene]-dimethylazanium;tetrafluoroborate Chemical compound F[B-](F)(F)F.CCOC(=O)C(\C#N)=N/OC(N(C)C)=[N+](C)C FPQVGDGSRVMNMR-JCTPKUEWSA-N 0.000 description 1
ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 description 1
238000010521 absorption reaction Methods 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
239000012346 acetyl chloride Substances 0.000 description 1
230000021736 acetylation Effects 0.000 description 1
238000006640 acetylation reaction Methods 0.000 description 1
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
239000012190 activator Substances 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
125000002252 acyl group Chemical group 0.000 description 1
230000001800 adrenalinergic effect Effects 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
239000003513 alkali Substances 0.000 description 1
229910001854 alkali hydroxide Inorganic materials 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
125000003545 alkoxy group Chemical group 0.000 description 1
150000001346 alkyl aryl ethers Chemical group 0.000 description 1
125000004414 alkyl thio group Chemical group 0.000 description 1
239000002160 alpha blocker Substances 0.000 description 1
AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
238000005576 amination reaction Methods 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
150000003868 ammonium compounds Chemical class 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
239000002369 angiotensin antagonist Substances 0.000 description 1
229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
239000010775 animal oil Substances 0.000 description 1
238000005349 anion exchange Methods 0.000 description 1
230000003266 anti-allergic effect Effects 0.000 description 1
230000001142 anti-diarrhea Effects 0.000 description 1
230000002785 anti-thrombosis Effects 0.000 description 1
239000003146 anticoagulant agent Substances 0.000 description 1
239000002518 antifoaming agent Substances 0.000 description 1
229940030600 antihypertensive agent Drugs 0.000 description 1
239000002220 antihypertensive agent Substances 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
239000003699 antiulcer agent Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
125000001204 arachidyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
238000006172 aromatic nitration reaction Methods 0.000 description 1
208000006673 asthma Diseases 0.000 description 1
210000003050 axon Anatomy 0.000 description 1
229950001786 azimilide Drugs 0.000 description 1
229940049706 benzodiazepine Drugs 0.000 description 1
125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 1
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
239000002876 beta blocker Substances 0.000 description 1
UUQMNUMQCIQDMZ-UHFFFAOYSA-N betahistine Chemical compound CNCCC1=CC=CC=N1 UUQMNUMQCIQDMZ-UHFFFAOYSA-N 0.000 description 1
230000003115 biocidal effect Effects 0.000 description 1
230000031018 biological processes and functions Effects 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
GRSTVVGJSKHCCS-UHFFFAOYSA-N bis(1h-imidazol-2-yl)methanone Chemical compound N=1C=CNC=1C(=O)C1=NC=CN1 GRSTVVGJSKHCCS-UHFFFAOYSA-N 0.000 description 1
239000000872 buffer Substances 0.000 description 1
BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 1
KMGBZBJJOKUPIA-UHFFFAOYSA-N butyl iodide Chemical compound CCCCI KMGBZBJJOKUPIA-UHFFFAOYSA-N 0.000 description 1
229910052791 calcium Inorganic materials 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
239000002775 capsule Substances 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
229960000830 captopril Drugs 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
150000001728 carbonyl compounds Chemical class 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
230000000747 cardiac effect Effects 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
230000020411 cell activation Effects 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 1
150000001843 chromanes Chemical class 0.000 description 1
QZHPTGXQGDFGEN-UHFFFAOYSA-N chromene Chemical compound C1=CC=C2C=C[CH]OC2=C1 QZHPTGXQGDFGEN-UHFFFAOYSA-N 0.000 description 1
229910052804 chromium Inorganic materials 0.000 description 1
239000011651 chromium Substances 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
238000003776 cleavage reaction Methods 0.000 description 1
239000003026 cod liver oil Substances 0.000 description 1
235000012716 cod liver oil Nutrition 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
150000001983 dialkylethers Chemical class 0.000 description 1
XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 description 1
229940075557 diethylene glycol monoethyl ether Drugs 0.000 description 1
229940082657 digitalis glycosides Drugs 0.000 description 1
229940113088 dimethylacetamide Drugs 0.000 description 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
239000002934 diuretic Substances 0.000 description 1
229940030606 diuretics Drugs 0.000 description 1
CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
239000008298 dragée Substances 0.000 description 1
239000013583 drug formulation Substances 0.000 description 1
238000002651 drug therapy Methods 0.000 description 1
210000001198 duodenum Anatomy 0.000 description 1
239000000975 dye Substances 0.000 description 1
230000002526 effect on cardiovascular system Effects 0.000 description 1
238000007336 electrophilic substitution reaction Methods 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
229960000873 enalapril Drugs 0.000 description 1
GKIPXFAANLTWBM-UHFFFAOYSA-N epibromohydrin Chemical compound BrCC1CO1 GKIPXFAANLTWBM-UHFFFAOYSA-N 0.000 description 1
XDKHDACSBYUBRT-UHFFFAOYSA-N ethyl 2-[4-[(2,2-dimethyl-6-phenylmethoxy-3,4-dihydrochromen-4-yl)-methylsulfonylamino]butoxy]acetate Chemical compound C(C1=CC=CC=C1)OC=1C=C2C(CC(OC2=CC1)(C)C)N(CCCCOCC(=O)OCC)S(=O)(=O)C XDKHDACSBYUBRT-UHFFFAOYSA-N 0.000 description 1
XTASFFFIVXSHPK-UHFFFAOYSA-N ethyl 4-[(2,2-dimethyl-6-phenylmethoxy-3,4-dihydrochromen-4-yl)-methylsulfonylamino]butanoate Chemical compound C1=C2C(N(CCCC(=O)OCC)S(C)(=O)=O)CC(C)(C)OC2=CC=C1OCC1=CC=CC=C1 XTASFFFIVXSHPK-UHFFFAOYSA-N 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
238000000605 extraction Methods 0.000 description 1
229960001596 famotidine Drugs 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
239000011737 fluorine Substances 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
125000000524 functional group Chemical group 0.000 description 1
239000007789 gas Substances 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
239000000499 gel Substances 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
150000008282 halocarbons Chemical class 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
230000026030 halogenation Effects 0.000 description 1
238000005658 halogenation reaction Methods 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
150000004679 hydroxides Chemical class 0.000 description 1
150000002440 hydroxy compounds Chemical class 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
WCYJQVALWQMJGE-UHFFFAOYSA-M hydroxylammonium chloride Chemical compound [Cl-].O[NH3+] WCYJQVALWQMJGE-UHFFFAOYSA-M 0.000 description 1
230000002102 hyperpolarization Effects 0.000 description 1
150000007928 imidazolide derivatives Chemical class 0.000 description 1
230000006872 improvement Effects 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
239000003701 inert diluent Substances 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
230000000297 inotrophic effect Effects 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
238000011835 investigation Methods 0.000 description 1
239000011630 iodine Substances 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
238000002955 isolation Methods 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
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000011989 jacobsen's catalyst Substances 0.000 description 1
150000003893 lactate salts Chemical class 0.000 description 1
150000007517 lewis acids Chemical class 0.000 description 1
239000007788 liquid 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
159000000003 magnesium salts Chemical class 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
125000002960 margaryl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
238000003328 mesylation reaction Methods 0.000 description 1
229910052987 metal hydride Inorganic materials 0.000 description 1
150000004681 metal hydrides Chemical class 0.000 description 1
HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 1
125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
NOHLXXSBHARBLK-UHFFFAOYSA-N methyl 2-[(2,2-dimethyl-6-phenylmethoxy-3,4-dihydrochromen-4-yl)-methylsulfonylamino]acetate Chemical compound C1=C2C(N(CC(=O)OC)S(C)(=O)=O)CC(C)(C)OC2=CC=C1OCC1=CC=CC=C1 NOHLXXSBHARBLK-UHFFFAOYSA-N 0.000 description 1
DNKQOXJZWXJQRC-UHFFFAOYSA-N methyl 5-[methylsulfonyl-(2,2,6-trimethyl-3,4-dihydrochromen-4-yl)amino]pentanoate Chemical compound C1=C(C)C=C2C(N(CCCCC(=O)OC)S(C)(=O)=O)CC(C)(C)OC2=C1 DNKQOXJZWXJQRC-UHFFFAOYSA-N 0.000 description 1
RAVVJKCSZXAIQP-UHFFFAOYSA-N methyl 5-bromopentanoate Chemical compound COC(=O)CCCCBr RAVVJKCSZXAIQP-UHFFFAOYSA-N 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
229960000282 metronidazole Drugs 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000002156 mixing Methods 0.000 description 1
125000000896 monocarboxylic acid group Chemical group 0.000 description 1
230000004118 muscle contraction Effects 0.000 description 1
230000036640 muscle relaxation Effects 0.000 description 1
230000002107 myocardial effect Effects 0.000 description 1
125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
UDGSVBYJWHOHNN-UHFFFAOYSA-N n',n'-diethylethane-1,2-diamine Chemical compound CCN(CC)CCN UDGSVBYJWHOHNN-UHFFFAOYSA-N 0.000 description 1
LIUGRXFEJOSPIA-UHFFFAOYSA-N n'-benzyl-n'-methylethane-1,2-diamine Chemical compound NCCN(C)CC1=CC=CC=C1 LIUGRXFEJOSPIA-UHFFFAOYSA-N 0.000 description 1
PEECTLLHENGOKU-UHFFFAOYSA-N n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC=C1.CN(C)C1=CC=NC=C1 PEECTLLHENGOKU-UHFFFAOYSA-N 0.000 description 1
MEXAMNDFMULUSR-UHFFFAOYSA-N n-(1h-benzimidazol-2-ylmethyl)-2-[ethylsulfonyl-(6-fluoro-2,2-dimethyl-3,4-dihydrochromen-4-yl)amino]acetamide Chemical compound C1C(C)(C)OC2=CC=C(F)C=C2C1N(S(=O)(=O)CC)CC(=O)NCC1=NC2=CC=CC=C2N1 MEXAMNDFMULUSR-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
FOMDVZNBIAHGSG-UHFFFAOYSA-N n-(2,2,6-trimethyl-3,4-dihydrochromen-4-yl)methanesulfonamide Chemical compound O1C(C)(C)CC(NS(C)(=O)=O)C2=CC(C)=CC=C21 FOMDVZNBIAHGSG-UHFFFAOYSA-N 0.000 description 1
WFHBWWQQLKDHSF-UHFFFAOYSA-N n-(2,2-diethyl-6-methyl-3,4-dihydrochromen-4-yl)ethanesulfonamide Chemical compound CC1=CC=C2OC(CC)(CC)CC(NS(=O)(=O)CC)C2=C1 WFHBWWQQLKDHSF-UHFFFAOYSA-N 0.000 description 1
QOUQWVRCKAWLJA-UHFFFAOYSA-N n-(2,2-dimethyl-6-phenylmethoxy-3,4-dihydrochromen-4-yl)-n-[2-(2-methoxyethoxy)ethyl]methanesulfonamide Chemical compound C1=C2C(N(CCOCCOC)S(C)(=O)=O)CC(C)(C)OC2=CC=C1OCC1=CC=CC=C1 QOUQWVRCKAWLJA-UHFFFAOYSA-N 0.000 description 1
GXSFLKUIWWZBLR-UHFFFAOYSA-N n-(2,2-dimethyl-6-phenylmethoxy-3h-chromen-4-ylidene)hydroxylamine Chemical compound C=1C=C2OC(C)(C)CC(=NO)C2=CC=1OCC1=CC=CC=C1 GXSFLKUIWWZBLR-UHFFFAOYSA-N 0.000 description 1
IVEUAKIYTZWKOS-UHFFFAOYSA-N n-(2-ethylpyrazol-3-yl)-2-[ethylsulfonyl-(6-fluoro-2,2-dimethyl-3,4-dihydrochromen-4-yl)amino]acetamide Chemical compound CCN1N=CC=C1NC(=O)CN(S(=O)(=O)CC)C1C2=CC(F)=CC=C2OC(C)(C)C1 IVEUAKIYTZWKOS-UHFFFAOYSA-N 0.000 description 1
WDFHUZCLMDACOW-UHFFFAOYSA-N n-(6-chloro-3-hydroxy-2,2-dimethyl-3,4-dihydrochromen-4-yl)methanesulfonamide Chemical compound C1=C(Cl)C=C2C(NS(C)(=O)=O)C(O)C(C)(C)OC2=C1 WDFHUZCLMDACOW-UHFFFAOYSA-N 0.000 description 1
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 1
ZFRAJSFNRPKIPY-UHFFFAOYSA-N n-(diaminomethylidene)-2-[ethylsulfonyl-(6-fluoro-2,2-dimethyl-3,4-dihydrochromen-4-yl)amino]acetamide Chemical compound C1=C(F)C=C2C(N(CC(=O)N=C(N)N)S(=O)(=O)CC)CC(C)(C)OC2=C1 ZFRAJSFNRPKIPY-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
XRKQMIFKHDXFNQ-UHFFFAOYSA-N n-cyclohexyl-n-ethylcyclohexanamine Chemical compound C1CCCCC1N(CC)C1CCCCC1 XRKQMIFKHDXFNQ-UHFFFAOYSA-N 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
HNBDRPTVWVGKBR-UHFFFAOYSA-N n-pentanoic acid methyl ester Natural products CCCCC(=O)OC HNBDRPTVWVGKBR-UHFFFAOYSA-N 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000001196 nonadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000000269 nucleophilic effect Effects 0.000 description 1
238000010534 nucleophilic substitution reaction Methods 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000001451 organic peroxides Chemical class 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
125000002958 pentadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
238000003408 phase transfer catalysis Methods 0.000 description 1
229940117803 phenethylamine Drugs 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
239000002504 physiological saline solution Substances 0.000 description 1
239000003495 polar organic solvent Substances 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920001451 polypropylene glycol Polymers 0.000 description 1
230000009090 positive inotropic effect Effects 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
230000003389 potentiating effect Effects 0.000 description 1
239000010970 precious metal Substances 0.000 description 1
239000002243 precursor Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002265 prevention Effects 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
230000001536 pro-arrhythmogenic effect Effects 0.000 description 1
230000008569 process Effects 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
239000003380 propellant Substances 0.000 description 1
229940080818 propionamide Drugs 0.000 description 1
239000003586 protic polar solvent Substances 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 description 1
125000000714 pyrimidinyl group Chemical group 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
229960003401 ramipril Drugs 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
102000005962 receptors Human genes 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
238000006268 reductive amination reaction Methods 0.000 description 1
230000002040 relaxant effect Effects 0.000 description 1
230000002336 repolarization Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
230000004044 response Effects 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
230000007017 scission Effects 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
230000028327 secretion Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
210000000329 smooth muscle myocyte Anatomy 0.000 description 1
239000000050 smooth muscle relaxant Substances 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
229960002370 sotalol Drugs 0.000 description 1
150000003413 spiro compounds Chemical class 0.000 description 1
239000007921 spray Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008107 starch Substances 0.000 description 1
125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
125000000565 sulfonamide group Chemical group 0.000 description 1
150000003458 sulfonic acid derivatives Chemical class 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000002600 sunflower oil Substances 0.000 description 1
239000002511 suppository base Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000003826 tablet Substances 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
238000012546 transfer Methods 0.000 description 1
230000009466 transformation Effects 0.000 description 1
125000002889 tridecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000001960 triggered effect Effects 0.000 description 1
125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000002792 vascular Effects 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
235000013311 vegetables Nutrition 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- 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
- 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
- C07D311/72—3,4-Dihydro derivatives having in position 2 at least one methyl radical and in position 6 one oxygen atom, e.g. tocopherols
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Public Health (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Hospice & Palliative Care (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Pyrane Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

NO19984475A 1997-09-26 1998-09-25 Sulfonamidsubstituerte kromaner, deres anvendelse som medikament samt farmasoytiske preparater inneholdende forbindelsene. NO319563B1 (no)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DE19742509A DE19742509A1 (de)	1997-09-26	1997-09-26	Sulfonamid-substituierte Chromane, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltende pharmazeutische Zubereitungen

Publications (3)

Publication Number	Publication Date
NO984475D0 NO984475D0 (no)	1998-09-25
NO984475L NO984475L (no)	1999-03-29
NO319563B1 true NO319563B1 (no)	2005-08-29

Family

ID=7843709

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19984475A NO319563B1 (no)	1997-09-26	1998-09-25	Sulfonamidsubstituerte kromaner, deres anvendelse som medikament samt farmasoytiske preparater inneholdende forbindelsene.

Country Status (29)

Country	Link
US (1)	US5955607A (id)
EP (1)	EP0905131B1 (id)
JP (1)	JP4279920B2 (id)
KR (1)	KR19990030119A (id)
CN (1)	CN1212964A (id)
AR (1)	AR013518A1 (id)
AT (1)	ATE215942T1 (id)
AU (1)	AU741810B2 (id)
BR (1)	BR9803974A (id)
CA (1)	CA2249074A1 (id)
CZ (1)	CZ293681B6 (id)
DE (2)	DE19742509A1 (id)
DK (1)	DK0905131T3 (id)
ES (1)	ES2175582T3 (id)
HR (1)	HRP980527B1 (id)
HU (1)	HU224029B1 (id)
ID (1)	ID20968A (id)
IL (1)	IL126279A (id)
MY (1)	MY119575A (id)
NO (1)	NO319563B1 (id)
NZ (1)	NZ332029A (id)
PL (1)	PL328855A1 (id)
PT (1)	PT905131E (id)
RU (1)	RU2208611C2 (id)
SI (1)	SI0905131T1 (id)
SK (1)	SK282955B6 (id)
TR (1)	TR199801902A3 (id)
TW (1)	TW517053B (id)
ZA (1)	ZA988790B (id)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
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
IL141341A0 (en) *	1998-09-04	2002-03-10	Procter & Gamble	Substituted dihydrobenzopyrans useful as antiarrhythmic agents
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
US8225458B1 (en)	2001-07-13	2012-07-24	Hoffberg Steven M	Intelligent door restraint
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
DE10348298A1 (de) *	2003-10-17	2005-05-19	Solvay Pharmaceuticals Gmbh	Amidomethyl-substituierte 2-(4-Sulfonylamino)-3-hydroxy-3,4-dihydro-2H-chromen-6-ylderivade, Verfahren und Zwischenprodukte zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel

Family Cites Families (8)

* Cited by examiner, † Cited by third party
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
US5104890A (en) *	1989-03-28	1992-04-14	Fujisawa Pharmaceutical Company, Ltd.	Benzopyran derivatives and processes for preparation thereof
AU651105B2 (en) *	1990-06-18	1994-07-14	E.R. Squibb & Sons, Inc.	Benzopyran derivatives and heterocyclic analogs thereof as antiischemic agents
EP0471515B1 (en) *	1990-08-15	1997-03-05	Eli Lilly And Company	Ring-substituted 2-amino-1,2,3,4-tetra-hydronaphthalenes, 3-aminochromanes and 3-aminothiochromanes
CA2070243A1 (en) *	1991-06-14	1992-12-15	Akira Shiozawa	Chroman derivatives
US5428031A (en) *	1991-12-03	1995-06-27	Merck & Co., Inc.	Methods of treating cardiac arrhythmia
TW496866B (en) *	1996-05-15	2002-08-01	Hoechst Ag	Sulfonamide-substituted chromans, processes for their preparation, their use as a medicament or a diagnostic, and medicament comprising them
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

1997
- 1997-09-26 DE DE19742509A patent/DE19742509A1/de not_active Withdrawn
1998
- 1998-09-17 IL IL12627998A patent/IL126279A/en not_active IP Right Cessation
- 1998-09-19 DK DK98117809T patent/DK0905131T3/da active
- 1998-09-19 AT AT98117809T patent/ATE215942T1/de not_active IP Right Cessation
- 1998-09-19 EP EP98117809A patent/EP0905131B1/de not_active Expired - Lifetime
- 1998-09-19 PT PT98117809T patent/PT905131E/pt unknown
- 1998-09-19 DE DE59803704T patent/DE59803704D1/de not_active Expired - Lifetime
- 1998-09-19 ES ES98117809T patent/ES2175582T3/es not_active Expired - Lifetime
- 1998-09-19 SI SI9830203T patent/SI0905131T1/xx unknown
- 1998-09-22 CN CN98119538A patent/CN1212964A/zh active Pending
- 1998-09-24 SK SK1319-98A patent/SK282955B6/sk unknown
- 1998-09-24 MY MYPI98004390A patent/MY119575A/en unknown
- 1998-09-24 NZ NZ332029A patent/NZ332029A/xx unknown
- 1998-09-24 TR TR1998/01902A patent/TR199801902A3/tr unknown
- 1998-09-24 ID IDP981280A patent/ID20968A/id unknown
- 1998-09-24 CZ CZ19983069A patent/CZ293681B6/cs not_active IP Right Cessation
- 1998-09-24 AR ARP980104776A patent/AR013518A1/es unknown
- 1998-09-24 RU RU98117613/04A patent/RU2208611C2/ru not_active IP Right Cessation
- 1998-09-24 BR BR9803974-1A patent/BR9803974A/pt not_active Application Discontinuation
- 1998-09-25 CA CA002249074A patent/CA2249074A1/en not_active Abandoned
- 1998-09-25 NO NO19984475A patent/NO319563B1/no unknown
- 1998-09-25 ZA ZA988790A patent/ZA988790B/xx unknown
- 1998-09-25 HU HU9802156A patent/HU224029B1/hu not_active IP Right Cessation
- 1998-09-25 AU AU87083/98A patent/AU741810B2/en not_active Ceased
- 1998-09-25 US US09/160,304 patent/US5955607A/en not_active Expired - Lifetime
- 1998-09-25 JP JP27216798A patent/JP4279920B2/ja not_active Expired - Lifetime
- 1998-09-25 PL PL98328855A patent/PL328855A1/xx unknown
- 1998-09-25 HR HR980527A patent/HRP980527B1/xx not_active IP Right Cessation
- 1998-09-25 KR KR1019980039835A patent/KR19990030119A/ko not_active Abandoned
- 1998-10-22 TW TW087115866A patent/TW517053B/zh active

Also Published As

Publication number	Publication date
AU741810B2 (en)	2001-12-13
HU224029B1 (hu)	2005-05-30
TR199801902A2 (xx)	1999-04-21
PT905131E (pt)	2002-09-30
JPH11158170A (ja)	1999-06-15
AU8708398A (en)	1999-04-15
RU2208611C2 (ru)	2003-07-20
CZ306998A3 (cs)	1999-04-14
ES2175582T3 (es)	2002-11-16
SK131998A3 (en)	1999-06-11
SK282955B6 (sk)	2003-01-09
PL328855A1 (en)	1999-03-29
HRP980527B1 (en)	2002-12-31
JP4279920B2 (ja)	2009-06-17
ID20968A (id)	1999-04-01
IL126279A (en)	2002-08-14
HUP9802156A3 (en)	2001-05-28
SI0905131T1 (en)	2002-10-31
CZ293681B6 (cs)	2004-06-16
US5955607A (en)	1999-09-21
MY119575A (en)	2005-06-30
EP0905131A1 (de)	1999-03-31
HRP980527A2 (en)	1999-06-30
KR19990030119A (ko)	1999-04-26
ZA988790B (en)	1999-03-26
TW517053B (en)	2003-01-11
HUP9802156A2 (hu)	2001-04-28
NZ332029A (en)	2000-04-28
CN1212964A (zh)	1999-04-07
TR199801902A3 (tr)	1999-04-21
NO984475D0 (no)	1998-09-25
DK0905131T3 (da)	2002-07-15
CA2249074A1 (en)	1999-03-26
EP0905131B1 (de)	2002-04-10
AR013518A1 (es)	2000-12-27
HU9802156D0 (en)	1998-11-30
DE19742509A1 (de)	1999-04-01
DE59803704D1 (de)	2002-05-16
ATE215942T1 (de)	2002-04-15
IL126279A0 (en)	1999-05-09
BR9803974A (pt)	2000-05-09
NO984475L (no)	1999-03-29

Publication	Publication Date	Title
JP4422222B2 (ja)	2010-02-24	スルホンアミド置換クロマン、その製法、医薬としてのその使用およびそれを含有する医薬製剤
ES2234044T3 (es)	2005-06-16	Compuestos anulares de siete miembros, condensados sustituidos con sulfonamido con actividad bloqueante del canal de potasio.
US6008245A (en)	1999-12-28	Sulfonamide-substituted benzopyran derivatives, processes for their preparation, their use as a medicament, and pharmaceutical preparations comprising them
US6015822A (en)	2000-01-18	Sulfonamide-substituted fused 5-membered ring compounds, their use as a medicament, and pharmaceutical preparations comprising them
US5955607A (en)	1999-09-21	Sulfonamide-substituted chromans, processes for their preparation, their use as a medicament or diagnostic, and pharmaceutical preparations comprising them
US6333349B1 (en)	2001-12-25	Sulfonamide-substituted fused 7-membered ring compounds, their use as a medicament, and pharmaceutical preparations comprising them
MXPA98009370A (en)	1999-06-01	Condensed compounds with 5 members ring, substituted with sulfonamide, its use comomedicamentos, as well as pharmaceutical preparations that contains them
HK1015787A (en)	1999-10-22	Sulfonamide-substituted fused 7-membered ring compounds, their use as a medicament, and pharmaceutical preparations comprising them