ES2295360T3 - Amidas de acido antranilico con cadena lateral de heteroarilsulfonilo y su uso como principios activos antiarritmicos. - Google Patents
Amidas de acido antranilico con cadena lateral de heteroarilsulfonilo y su uso como principios activos antiarritmicos. Download PDFInfo
- Publication number
- ES2295360T3 ES2295360T3 ES02745333T ES02745333T ES2295360T3 ES 2295360 T3 ES2295360 T3 ES 2295360T3 ES 02745333 T ES02745333 T ES 02745333T ES 02745333 T ES02745333 T ES 02745333T ES 2295360 T3 ES2295360 T3 ES 2295360T3
- Authority
- ES
- Spain
- Prior art keywords
- atoms
- quad
- phenyl
- alkyl
- naphthyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 title description 9
- -1 dimethylamino, sulfamoyl Chemical group 0.000 claims abstract description 219
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 150
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 146
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 146
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 140
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 140
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 140
- 239000001257 hydrogen Substances 0.000 claims abstract description 136
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 136
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 126
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims abstract description 113
- 125000001424 substituent group Chemical group 0.000 claims abstract description 95
- 150000001875 compounds Chemical class 0.000 claims abstract description 93
- 125000004429 atom Chemical group 0.000 claims abstract description 72
- 150000003839 salts Chemical class 0.000 claims abstract description 56
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 42
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims abstract description 34
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 29
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 14
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 14
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 104
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 78
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 41
- 125000001041 indolyl group Chemical group 0.000 claims description 41
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 41
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 41
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 41
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 41
- 125000004076 pyridyl group Chemical group 0.000 claims description 41
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 41
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 41
- 125000005493 quinolyl group Chemical group 0.000 claims description 41
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 41
- 229910052799 carbon Inorganic materials 0.000 claims description 40
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 32
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 28
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 26
- 239000003814 drug Substances 0.000 claims description 19
- 239000000126 substance Substances 0.000 claims description 15
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
- 229940079593 drug Drugs 0.000 claims description 14
- 238000002360 preparation method Methods 0.000 claims description 14
- 125000002541 furyl group Chemical group 0.000 claims description 13
- 125000001544 thienyl group Chemical group 0.000 claims description 13
- 206010003658 Atrial Fibrillation Diseases 0.000 claims description 11
- 239000004480 active ingredient Substances 0.000 claims description 11
- 230000001746 atrial effect Effects 0.000 claims description 8
- 238000011321 prophylaxis Methods 0.000 claims description 7
- 238000002560 therapeutic procedure Methods 0.000 claims description 7
- 206010003119 arrhythmia Diseases 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 230000036982 action potential Effects 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 4
- 230000006793 arrhythmia Effects 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
- 239000000654 additive Substances 0.000 claims description 3
- 230000033764 rhythmic process Effects 0.000 claims description 2
- 230000000747 cardiac effect Effects 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000000144 pharmacologic effect Effects 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 abstract 2
- 239000000460 chlorine Substances 0.000 description 72
- 239000000243 solution Substances 0.000 description 42
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 35
- 239000002243 precursor Substances 0.000 description 34
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
- 150000001412 amines Chemical class 0.000 description 31
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
- 239000002253 acid Substances 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 239000000203 mixture Substances 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 239000007787 solid Substances 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 13
- 239000002904 solvent Substances 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 239000003416 antiarrhythmic agent Substances 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- 239000007832 Na2SO4 Substances 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 235000019198 oils Nutrition 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- 101001026214 Homo sapiens Potassium voltage-gated channel subfamily A member 5 Proteins 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- 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 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- 230000003288 anthiarrhythmic effect Effects 0.000 description 6
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- JUYUYCIJACTHMK-UHFFFAOYSA-N quinoline-8-sulfonyl chloride Chemical compound C1=CN=C2C(S(=O)(=O)Cl)=CC=CC2=C1 JUYUYCIJACTHMK-UHFFFAOYSA-N 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- NNJBQTDFDVLWEQ-UHFFFAOYSA-N 2-(sulfonylamino)benzoic acid Chemical class OC(=O)C1=CC=CC=C1N=S(=O)=O NNJBQTDFDVLWEQ-UHFFFAOYSA-N 0.000 description 5
- PXBFMLJZNCDSMP-UHFFFAOYSA-N 2-Aminobenzamide Chemical class NC(=O)C1=CC=CC=C1N PXBFMLJZNCDSMP-UHFFFAOYSA-N 0.000 description 5
- 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 5
- 108091006146 Channels Proteins 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- 239000002671 adjuvant Substances 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 230000003111 delayed effect Effects 0.000 description 5
- 235000019439 ethyl acetate Nutrition 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000000903 blocking effect Effects 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- 210000002837 heart atrium Anatomy 0.000 description 4
- 238000002483 medication Methods 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- YLNWJSHBHAFMAT-UHFFFAOYSA-N 1-(5-methylfuran-2-yl)propan-1-amine Chemical compound CCC(N)C1=CC=C(C)O1 YLNWJSHBHAFMAT-UHFFFAOYSA-N 0.000 description 3
- SSOCGBMGAODFEA-UHFFFAOYSA-N 2-(sulfonylamino)benzoyl chloride Chemical class ClC(=O)C1=CC=CC=C1N=S(=O)=O SSOCGBMGAODFEA-UHFFFAOYSA-N 0.000 description 3
- RSFXOPDETMHJCK-HNNXBMFYSA-N 2-amino-n-[(1s)-1-phenylpropyl]benzamide Chemical compound N([C@@H](CC)C=1C=CC=CC=1)C(=O)C1=CC=CC=C1N RSFXOPDETMHJCK-HNNXBMFYSA-N 0.000 description 3
- TUNNNFLDZNSBQK-UHFFFAOYSA-N 5-fluoro-2-(quinolin-8-ylsulfonylamino)benzoic acid Chemical compound OC(=O)C1=CC(F)=CC=C1NS(=O)(=O)C1=CC=CC2=CC=CN=C12 TUNNNFLDZNSBQK-UHFFFAOYSA-N 0.000 description 3
- 206010003130 Arrhythmia supraventricular Diseases 0.000 description 3
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 230000002425 cardiocirculatory effect Effects 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- QTUNRTDRPMOQNG-UHFFFAOYSA-N cyclopropyl(phenyl)methanamine;hydron;chloride Chemical compound Cl.C=1C=CC=CC=1C(N)C1CC1 QTUNRTDRPMOQNG-UHFFFAOYSA-N 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000003995 emulsifying agent Substances 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- YKRXJFHSEYGWQY-UHFFFAOYSA-N n-[(1-methylimidazol-2-yl)methyl]-1-phenylmethanamine Chemical compound CN1C=CN=C1CNCC1=CC=CC=C1 YKRXJFHSEYGWQY-UHFFFAOYSA-N 0.000 description 3
- WIKJAZKXHCHEGC-UHFFFAOYSA-N n-cyclopropyl-n-methylpyridin-2-amine;hydrochloride Chemical compound Cl.C=1C=CC=NC=1N(C)C1CC1 WIKJAZKXHCHEGC-UHFFFAOYSA-N 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 238000002953 preparative HPLC Methods 0.000 description 3
- 230000001536 pro-arrhythmogenic effect Effects 0.000 description 3
- 150000003335 secondary amines Chemical class 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 3
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- AQFLVLHRZFLDDV-VIFPVBQESA-N (1s)-1-phenylpropan-1-amine Chemical compound CC[C@H](N)C1=CC=CC=C1 AQFLVLHRZFLDDV-VIFPVBQESA-N 0.000 description 2
- GGUMJDNMKLAOQA-UHFFFAOYSA-N 1-cyclopropyl-1-(6-methoxypyridin-2-yl)-n-phenylmethoxymethanamine Chemical compound COC1=CC=CC(C(NOCC=2C=CC=CC=2)C2CC2)=N1 GGUMJDNMKLAOQA-UHFFFAOYSA-N 0.000 description 2
- ZIUBMNMRMGMHGW-UHFFFAOYSA-N 1-cyclopropyl-n-phenylmethoxymethanimine Chemical compound C=1C=CC=CC=1CON=CC1CC1 ZIUBMNMRMGMHGW-UHFFFAOYSA-N 0.000 description 2
- PALFZIMHIMRYFF-UHFFFAOYSA-N 1-cyclopropyl-n-pyridin-2-ylmethanimine Chemical compound C1CC1C=NC1=CC=CC=N1 PALFZIMHIMRYFF-UHFFFAOYSA-N 0.000 description 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- UEBFLTZXUXZPJO-UHFFFAOYSA-N 1-methylimidazole-2-carbaldehyde Chemical compound CN1C=CN=C1C=O UEBFLTZXUXZPJO-UHFFFAOYSA-N 0.000 description 2
- COHYOBKZKMKMIX-UHFFFAOYSA-N 1-phenyl-n-(pyridin-3-ylmethyl)methanamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CN=C1 COHYOBKZKMKMIX-UHFFFAOYSA-N 0.000 description 2
- VQGKOCARCUCUMC-UHFFFAOYSA-N 1-pyridin-3-ylpropan-1-amine Chemical compound CCC(N)C1=CC=CN=C1 VQGKOCARCUCUMC-UHFFFAOYSA-N 0.000 description 2
- VDNKJMUNLKAGAM-UHFFFAOYSA-N 1-pyridin-3-ylpropan-1-one Chemical compound CCC(=O)C1=CC=CN=C1 VDNKJMUNLKAGAM-UHFFFAOYSA-N 0.000 description 2
- JOTQNZHTWXIWHJ-UHFFFAOYSA-N 2-(quinolin-8-ylsulfonylamino)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1NS(=O)(=O)C1=CC=CC2=CC=CN=C12 JOTQNZHTWXIWHJ-UHFFFAOYSA-N 0.000 description 2
- DLDOXWDYWXYCLC-INIZCTEOSA-N 2-amino-5-methoxy-n-[(1s)-1-phenylpropyl]benzamide Chemical compound N([C@@H](CC)C=1C=CC=CC=1)C(=O)C1=CC(OC)=CC=C1N DLDOXWDYWXYCLC-INIZCTEOSA-N 0.000 description 2
- FWRBAPRINZNBIZ-UHFFFAOYSA-N 2-amino-5-methyl-n-[1-(5-methylfuran-2-yl)propyl]benzamide Chemical compound C=1C=C(C)OC=1C(CC)NC(=O)C1=CC(C)=CC=C1N FWRBAPRINZNBIZ-UHFFFAOYSA-N 0.000 description 2
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 2
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 2
- OSMDTSVVCZUJSX-UHFFFAOYSA-N 5-methoxy-2-[(6-methylpyridin-3-yl)sulfonylamino]-n-(1-phenylpropyl)benzamide Chemical compound C=1C=CC=CC=1C(CC)NC(=O)C1=CC(OC)=CC=C1NS(=O)(=O)C1=CC=C(C)N=C1 OSMDTSVVCZUJSX-UHFFFAOYSA-N 0.000 description 2
- KTDYNOKUFSRVDV-UHFFFAOYSA-N 5-methyl-n-[1-(5-methylfuran-2-yl)propyl]-2-(pyridin-2-ylsulfonylamino)benzamide Chemical compound C=1C=C(C)OC=1C(CC)NC(=O)C1=CC(C)=CC=C1NS(=O)(=O)C1=CC=CC=N1 KTDYNOKUFSRVDV-UHFFFAOYSA-N 0.000 description 2
- LDFISZJWVADWOR-UHFFFAOYSA-N 5-methyl-n-[1-(5-methylfuran-2-yl)propyl]-2-nitrobenzamide Chemical compound C=1C=C(C)OC=1C(CC)NC(=O)C1=CC(C)=CC=C1[N+]([O-])=O LDFISZJWVADWOR-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 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
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-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
- CPLXHLVBOLITMK-UHFFFAOYSA-N Magnesium oxide Chemical compound [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 2
- 102000004257 Potassium Channel Human genes 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 206010042600 Supraventricular arrhythmias Diseases 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
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- DYUUWOWDJOFYKC-UHFFFAOYSA-N n-[cyclopropyl(phenyl)methyl]-5-fluoro-2-(quinolin-8-ylsulfonylamino)benzamide Chemical compound C=1C(F)=CC=C(NS(=O)(=O)C=2C3=NC=CC=C3C=CC=2)C=1C(=O)NC(C=1C=CC=CC=1)C1CC1 DYUUWOWDJOFYKC-UHFFFAOYSA-N 0.000 description 1
- LAGYCULQKQSHMX-UHFFFAOYSA-N n-[cyclopropyl(phenyl)methyl]-5-methoxy-2-(quinolin-8-ylsulfonylamino)benzamide Chemical compound C=1C(OC)=CC=C(NS(=O)(=O)C=2C3=NC=CC=C3C=CC=2)C=1C(=O)NC(C=1C=CC=CC=1)C1CC1 LAGYCULQKQSHMX-UHFFFAOYSA-N 0.000 description 1
- ZGKBNWNTGFMMOL-UHFFFAOYSA-N n-[phenyl(pyridin-3-yl)methyl]-2-(quinolin-8-ylsulfonylamino)benzamide Chemical compound C=1C=CC=C(NS(=O)(=O)C=2C3=NC=CC=C3C=CC=2)C=1C(=O)NC(C=1C=NC=CC=1)C1=CC=CC=C1 ZGKBNWNTGFMMOL-UHFFFAOYSA-N 0.000 description 1
- PUHMXLKXQDOCFC-UHFFFAOYSA-N n-benzyl-3-imidazol-1-ylpropan-1-amine Chemical compound C1=CN=CN1CCCNCC1=CC=CC=C1 PUHMXLKXQDOCFC-UHFFFAOYSA-N 0.000 description 1
- HGCKEQOMTKMGHK-UHFFFAOYSA-N n-benzyl-n-(pyridin-2-ylmethyl)-2-(quinolin-8-ylsulfonylamino)benzamide Chemical compound C=1C=CC=C(NS(=O)(=O)C=2C3=NC=CC=C3C=CC=2)C=1C(=O)N(CC=1N=CC=CC=1)CC1=CC=CC=C1 HGCKEQOMTKMGHK-UHFFFAOYSA-N 0.000 description 1
- PPHSOCROFCONHN-UHFFFAOYSA-N n-benzyl-n-(pyridin-3-ylmethyl)-2-(quinolin-8-ylsulfonylamino)benzamide Chemical compound C=1C=CC=C(NS(=O)(=O)C=2C3=NC=CC=C3C=CC=2)C=1C(=O)N(CC=1C=NC=CC=1)CC1=CC=CC=C1 PPHSOCROFCONHN-UHFFFAOYSA-N 0.000 description 1
- RPEPHYHUHVMOFG-UHFFFAOYSA-N n-benzyl-n-[(1-methylimidazol-2-yl)methyl]-2-(quinolin-8-ylsulfonylamino)benzamide Chemical compound CN1C=CN=C1CN(C(=O)C=1C(=CC=CC=1)NS(=O)(=O)C=1C2=NC=CC=C2C=CC=1)CC1=CC=CC=C1 RPEPHYHUHVMOFG-UHFFFAOYSA-N 0.000 description 1
- DYAXICMTNLURRU-UHFFFAOYSA-N n-benzyl-n-cyclopropyl-2-(quinolin-8-ylsulfonylamino)benzamide Chemical compound C=1C=CC=C(NS(=O)(=O)C=2C3=NC=CC=C3C=CC=2)C=1C(=O)N(C1CC1)CC1=CC=CC=C1 DYAXICMTNLURRU-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
- NMRFEBKWDIFJNE-UHFFFAOYSA-N n-cyclohexyl-2-(quinolin-8-ylsulfonylamino)benzamide Chemical compound C=1C=CC=C(NS(=O)(=O)C=2C3=NC=CC=C3C=CC=2)C=1C(=O)NC1CCCCC1 NMRFEBKWDIFJNE-UHFFFAOYSA-N 0.000 description 1
- GFUKEKROWXOBQW-UHFFFAOYSA-N n-cyclopropyl-n-phenyl-2-(quinolin-8-ylsulfonylamino)benzamide Chemical compound C=1C=CC=C(NS(=O)(=O)C=2C3=NC=CC=C3C=CC=2)C=1C(=O)N(C=1C=CC=CC=1)C1CC1 GFUKEKROWXOBQW-UHFFFAOYSA-N 0.000 description 1
- WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- INKGFTSGGGUXDH-UHFFFAOYSA-N n-methyl-n-phenylpyridin-3-amine Chemical compound C=1C=CN=CC=1N(C)C1=CC=CC=C1 INKGFTSGGGUXDH-UHFFFAOYSA-N 0.000 description 1
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- 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
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 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
- XYEOALKITRFCJJ-UHFFFAOYSA-N o-benzylhydroxylamine Chemical compound NOCC1=CC=CC=C1 XYEOALKITRFCJJ-UHFFFAOYSA-N 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
- 150000007530 organic bases Chemical class 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- MPQXHAGKBWFSNV-UHFFFAOYSA-N oxidophosphanium Chemical class [PH3]=O MPQXHAGKBWFSNV-UHFFFAOYSA-N 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 229910052760 oxygen 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
- 230000002085 persistent effect Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000009090 positive inotropic effect Effects 0.000 description 1
- 239000003450 potassium channel blocker Substances 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
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000000039 preparative column chromatography Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000002035 prolonged effect Effects 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
- 230000000069 prophylactic effect Effects 0.000 description 1
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- XAJWHCVLZBSLNC-UHFFFAOYSA-N pyridin-1-ium-2-sulfonyl chloride;chloride Chemical compound Cl.ClS(=O)(=O)C1=CC=CC=N1 XAJWHCVLZBSLNC-UHFFFAOYSA-N 0.000 description 1
- HDOUGSFASVGDCS-UHFFFAOYSA-N pyridin-3-ylmethanamine Chemical compound NCC1=CC=CN=C1 HDOUGSFASVGDCS-UHFFFAOYSA-N 0.000 description 1
- JQJOGAGLBDBMLU-UHFFFAOYSA-N pyridine-2-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=N1 JQJOGAGLBDBMLU-UHFFFAOYSA-N 0.000 description 1
- WHMDPDGBKYUEMW-UHFFFAOYSA-N pyridine-2-thiol Chemical compound SC1=CC=CC=N1 WHMDPDGBKYUEMW-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- SXVRECLPTCOMIA-UHFFFAOYSA-N quinoline-8-sulfonic acid Chemical compound C1=CN=C2C(S(=O)(=O)O)=CC=CC2=C1 SXVRECLPTCOMIA-UHFFFAOYSA-N 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
- 230000036279 refractory period Effects 0.000 description 1
- 230000002336 repolarization Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004043 responsiveness 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
- GZKLJWGUPQBVJQ-UHFFFAOYSA-N sertindole Chemical compound C1=CC(F)=CC=C1N1C2=CC=C(Cl)C=C2C(C2CCN(CCN3C(NCC3)=O)CC2)=C1 GZKLJWGUPQBVJQ-UHFFFAOYSA-N 0.000 description 1
- 229960000652 sertindole Drugs 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229960002370 sotalol Drugs 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 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
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 229910052717 sulfur Inorganic materials 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
- 230000002459 sustained effect Effects 0.000 description 1
- 230000001975 sympathomimetic effect Effects 0.000 description 1
- 229940064707 sympathomimetics Drugs 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- CTIRHWCPXYGDGF-HDICACEKSA-N tedisamil Chemical compound [H][C@]12CN(CC3CC3)C[C@]([H])(CN(CC3CC3)C1)C21CCCC1 CTIRHWCPXYGDGF-HDICACEKSA-N 0.000 description 1
- 229960002926 tedisamil Drugs 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
- 150000003512 tertiary amines Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 125000001425 triazolyl group Chemical group 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
- 238000002604 ultrasonography Methods 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
- 235000013311 vegetables Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
-
- 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
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/36—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/12—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/30—Hetero atoms other than halogen
- C07D333/34—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
- Pyridine Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10128331A DE10128331A1 (de) | 2001-06-12 | 2001-06-12 | Anthranilsäureamide mit Heteroarylsulfonyl-Seitenkette, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltende pharmazeutische Zubereitungen |
| DE10128331 | 2001-06-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2295360T3 true ES2295360T3 (es) | 2008-04-16 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES02745333T Expired - Lifetime ES2295360T3 (es) | 2001-06-12 | 2002-05-31 | Amidas de acido antranilico con cadena lateral de heteroarilsulfonilo y su uso como principios activos antiarritmicos. |
Country Status (40)
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10128331A1 (de) * | 2001-06-12 | 2002-12-19 | Aventis Pharma Gmbh | Anthranilsäureamide mit Heteroarylsulfonyl-Seitenkette, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltende pharmazeutische Zubereitungen |
| US7119112B2 (en) * | 2002-02-28 | 2006-10-10 | Icagen, Inc. | Sulfonamides as potassium channel blockers |
| HRP20041131A2 (en) * | 2002-04-26 | 2005-08-31 | Ishihara Sangyo Kaisha Ltd. | Pyridine compounds or salts thereof and herbicides |
| EP1388535A1 (en) * | 2002-08-07 | 2004-02-11 | Aventis Pharma Deutschland GmbH | Acylated arylcycloalkylamines and their use as pharmaceuticals |
| DE10312061A1 (de) * | 2003-03-18 | 2004-09-30 | Aventis Pharma Deutschland Gmbh | Kombination von Phenylcarbonsäureamiden mit Blockern des IK-Kanals und deren Verwendung zur Behandlung von Vorhofarrhythmien |
| GB0315950D0 (en) | 2003-06-11 | 2003-08-13 | Xention Discovery Ltd | Compounds |
| EP1489071A1 (en) * | 2003-06-18 | 2004-12-22 | 4Sc Ag | N-substituted, 3,4-dihydro-1H-isoquinoline as potassium channels modulators |
| EP1651621B1 (en) | 2003-08-08 | 2008-08-06 | Janssen Pharmaceutica N.V. | 2- (quinoxalin-5-ylsulfonylamino) -benzamide compounds as cck2 modulators |
| DE10341233A1 (de) * | 2003-09-08 | 2005-03-24 | Aventis Pharma Deutschland Gmbh | Kombination von Phenylcarbonsäureamiden mit beta-Adrenozeptoren-Blockern und deren Verwendung zur Behandlung von Vorhofarrhythmien |
| DE102004009931A1 (de) * | 2004-02-26 | 2005-09-15 | Aventis Pharma Deutschland Gmbh | Kv1.5-Blocker zur selektiven Steigerung der Vorhofkontraktilität und Behandlung der Herzinsuffizienz |
| GB0412986D0 (en) | 2004-06-10 | 2004-07-14 | Xention Discovery Ltd | Compounds |
| US7569589B2 (en) | 2004-07-29 | 2009-08-04 | Merck & Co., Inc. | Potassium channel inhibitors |
| US7297816B2 (en) | 2004-09-24 | 2007-11-20 | Janssen Pharmaceutica N.V. | Sulfonamide compounds |
| US7576212B2 (en) | 2004-12-09 | 2009-08-18 | Xention Limited | Thieno[2,3-B] pyridines as potassium channel inhibitors |
| GB0525164D0 (en) | 2005-12-09 | 2006-01-18 | Xention Discovery Ltd | Compounds |
| CN101636154B (zh) * | 2006-04-27 | 2011-12-14 | 塞诺菲-安万特德国有限公司 | Task-1和task-3离子通道抑制剂 |
| WO2008124524A2 (en) * | 2007-04-03 | 2008-10-16 | Janssen Pharmaceutica N.V. | Aryl sulfonamide compounds as modulators of the cck2 receptor |
| GB0815784D0 (en) | 2008-08-29 | 2008-10-08 | Xention Ltd | Novel potassium channel blockers |
| GB0815781D0 (en) | 2008-08-29 | 2008-10-08 | Xention Ltd | Novel potassium channel blockers |
| GB0815782D0 (en) | 2008-08-29 | 2008-10-08 | Xention Ltd | Novel potassium channel blockers |
| EP2448909B1 (en) * | 2009-06-29 | 2013-05-01 | Merz Pharma GmbH & Co. KGaA | Method of preparing 1-amino-1,3,3,5,5-pentamethylcyclohexane |
| PE20120693A1 (es) | 2009-06-29 | 2012-07-04 | Agios Pharmaceuticals Inc | Compuestos heterociclos como moduladores de la piruvato cinasa m2 (pkm2) |
| WO2011010132A1 (en) * | 2009-07-21 | 2011-01-27 | Astrazeneca Ab | Sustained-release composition comprising compound 600 |
| RU2414893C1 (ru) * | 2009-11-11 | 2011-03-27 | Государственное образовательное учреждение высшего профессионального образования "Мордовский государственный университет им. Н.П. Огарева" | Четвертичное аммониевое производное новокаина, обладающее противоаритмической активностью, и способ его получения |
| FR2967674B1 (fr) * | 2010-11-23 | 2012-12-14 | Pf Medicament | Derives d'heteroarylsulfonamides, leur preparation et leur application en therapeutique humaine |
| GB201105659D0 (en) | 2011-04-01 | 2011-05-18 | Xention Ltd | Compounds |
| NO3175985T3 (enExample) | 2011-07-01 | 2018-04-28 | ||
| JP2015504923A (ja) | 2012-01-27 | 2015-02-16 | ギリアード サイエンシーズ， インコーポレイテッド | 後期ナトリウムイオンチャネル遮断剤およびカリウムイオンチャネル遮断剤を使用する併用療法 |
| US9701627B2 (en) * | 2014-06-16 | 2017-07-11 | University Of Maryland, Baltimore | LRRK2 GTP binding inhibitors for treatment of Parkinson's disease and neuroinflammatory disorders |
| JP7205830B2 (ja) * | 2017-08-07 | 2023-01-17 | 国立大学法人広島大学 | 新規アントラニル酸系化合物、並びにそれを用いたＰｉｎ１阻害剤、炎症性疾患の治療剤及び癌の治療剤 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2155662A1 (en) | 1993-12-27 | 1995-07-06 | Fumihiro Ozaki | Anthranilic acid derivative |
| US5670504A (en) | 1995-02-23 | 1997-09-23 | Merck & Co. Inc. | 2,6-diaryl pyridazinones with immunosuppressant activity |
| US6083986A (en) | 1996-07-26 | 2000-07-04 | Icagen, Inc. | Potassium channel inhibitors |
| DK173062B1 (da) | 1996-10-11 | 1999-12-13 | Krueger As I | Fremgangsmåde til fjernelse af opløste metaller og/eller metalloider fra et vandigt medium indeholdende samme og med et sto |
| US5969017A (en) | 1996-10-31 | 1999-10-19 | Merck & Co., Inc. | Methods of treating or preventing cardiac arrhythmia |
| US5935945A (en) | 1996-10-31 | 1999-08-10 | Merck & Co., Inc. | Methods of treating or preventing cardiac arrhythmia |
| TW523506B (en) | 1996-12-18 | 2003-03-11 | Ono Pharmaceutical Co | Sulfonamide or carbamide derivatives and drugs containing the same as active ingredients |
| CZ302691B6 (cs) | 1998-07-08 | 2011-09-07 | Sanofi - Aventis Deutschland GmbH | N-Arylamidová sloucenina, zpusob její prípravy, farmaceutický prostredek tuto slouceninu obsahující, tato sloucenina pro použití jako aktivátor a pro použití k terapii nebo profylaxi |
| JP2002523451A (ja) * | 1998-09-01 | 2002-07-30 | ブリストル−マイヤーズ スクイブ カンパニー | カリウムチャネル抑制剤および方法 |
| WO2000078145A1 (en) * | 1999-06-24 | 2000-12-28 | Smithkline Beecham Corporation | Macrophage scavenger receptor antagonists |
| DE19947457A1 (de) * | 1999-10-02 | 2001-04-05 | Aventis Pharma Gmbh | 2'-Substituierte 1,1'-Biphenyl-2-carbonamide, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament sowie enthaltende pharmazeutische Zubereitungen |
| US6531495B1 (en) | 1999-10-02 | 2003-03-11 | Aventis Pharma Deutschland Gmbh | 2′-Substituted 1,1′-biphenyl-2-carboxamides, processes for their preparation, their use as medicaments, and pharmaceutical preparations comprising them |
| DE10128331A1 (de) * | 2001-06-12 | 2002-12-19 | Aventis Pharma Gmbh | Anthranilsäureamide mit Heteroarylsulfonyl-Seitenkette, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament oder Diagnostikum sowie sie enthaltende pharmazeutische Zubereitungen |
-
2001
- 2001-06-12 DE DE10128331A patent/DE10128331A1/de not_active Withdrawn
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2002
- 2002-05-17 PE PE2002000419A patent/PE20021066A1/es not_active Application Discontinuation
- 2002-05-21 OA OA1200300333A patent/OA12631A/fr unknown
- 2002-05-31 RS YU97703A patent/RS97703A/sr unknown
- 2002-05-31 HR HR20031028A patent/HRP20031028A2/hr not_active Application Discontinuation
- 2002-05-31 BR BR0210374-5A patent/BR0210374A/pt not_active Application Discontinuation
- 2002-05-31 AT AT02745333T patent/ATE378318T1/de active
- 2002-05-31 CN CNB028118502A patent/CN1247544C/zh not_active Expired - Fee Related
- 2002-05-31 NZ NZ530081A patent/NZ530081A/en unknown
- 2002-05-31 PL PL02364371A patent/PL364371A1/xx not_active IP Right Cessation
- 2002-05-31 EP EP02745333A patent/EP1399423B9/de not_active Expired - Lifetime
- 2002-05-31 ES ES02745333T patent/ES2295360T3/es not_active Expired - Lifetime
- 2002-05-31 MX MXPA03010875A patent/MXPA03010875A/es active IP Right Grant
- 2002-05-31 UA UA2004010206A patent/UA75412C2/uk unknown
- 2002-05-31 AU AU2002316939A patent/AU2002316939B2/en not_active Ceased
- 2002-05-31 IL IL15924702A patent/IL159247A0/xx unknown
- 2002-05-31 DE DE50211213T patent/DE50211213D1/de not_active Expired - Lifetime
- 2002-05-31 CZ CZ20033361A patent/CZ20033361A3/cs unknown
- 2002-05-31 RU RU2004100302/04A patent/RU2293727C2/ru not_active IP Right Cessation
- 2002-05-31 HU HU0400159A patent/HUP0400159A3/hu unknown
- 2002-05-31 KR KR1020037016206A patent/KR100863924B1/ko not_active Expired - Fee Related
- 2002-05-31 DK DK02745333T patent/DK1399423T3/da active
- 2002-05-31 EE EEP200300558A patent/EE05196B1/xx not_active IP Right Cessation
- 2002-05-31 PT PT02745333T patent/PT1399423E/pt unknown
- 2002-05-31 CA CA2450076A patent/CA2450076C/en not_active Expired - Fee Related
- 2002-05-31 WO PCT/EP2002/005956 patent/WO2002100825A2/de not_active Ceased
- 2002-05-31 JP JP2003503594A patent/JP4422477B2/ja not_active Expired - Fee Related
- 2002-05-31 SK SK1522-2003A patent/SK15222003A3/sk unknown
- 2002-06-10 AR ARP020102178A patent/AR036045A1/es active IP Right Grant
- 2002-06-10 TW TW091112464A patent/TWI304400B/zh not_active IP Right Cessation
- 2002-06-11 MY MYPI20022165A patent/MY138341A/en unknown
- 2002-06-12 US US10/166,595 patent/US6903216B2/en not_active Expired - Lifetime
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2003
- 2003-07-08 TN TNPCT/EP2002/005956A patent/TNSN03134A1/en unknown
- 2003-10-31 ZA ZA200308520A patent/ZA200308520B/en unknown
- 2003-11-04 CR CR7140A patent/CR7140A/es not_active Application Discontinuation
- 2003-12-03 EC EC2003004883A patent/ECSP034883A/es unknown
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- 2003-12-08 NO NO20035450A patent/NO20035450D0/no not_active Application Discontinuation
- 2003-12-08 IL IL159247A patent/IL159247A/en not_active IP Right Cessation
- 2003-12-10 MA MA27434A patent/MA27037A1/fr unknown
- 2003-12-11 CO CO03108701A patent/CO5540283A2/es not_active Application Discontinuation
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- 2005-02-08 US US11/052,959 patent/US7235664B2/en not_active Expired - Lifetime
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