JPS6340784B2 - - Google Patents
Info
- Publication number
- JPS6340784B2 JPS6340784B2 JP53084613A JP8461378A JPS6340784B2 JP S6340784 B2 JPS6340784 B2 JP S6340784B2 JP 53084613 A JP53084613 A JP 53084613A JP 8461378 A JP8461378 A JP 8461378A JP S6340784 B2 JPS6340784 B2 JP S6340784B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- group
- amino
- phenyl
- indolyl
- 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
Links
- 150000001875 compounds Chemical class 0.000 claims description 37
- 239000002253 acid Substances 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 18
- -1 nitro, amino Chemical group 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 239000004480 active ingredient Substances 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims description 5
- 239000002220 antihypertensive agent Substances 0.000 claims description 5
- 229940030600 antihypertensive agent Drugs 0.000 claims description 5
- 125000001589 carboacyl group Chemical group 0.000 claims description 5
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
- CERWCJWMZZCJBR-UHFFFAOYSA-N 1-[[1-(1h-indol-3-yl)-2-methylpropan-2-yl]amino]-3-(2-methylphenoxy)propan-2-ol;hydrochloride Chemical compound Cl.CC1=CC=CC=C1OCC(O)CNC(C)(C)CC1=CNC2=CC=CC=C12 CERWCJWMZZCJBR-UHFFFAOYSA-N 0.000 claims description 2
- 125000003917 carbamoyl group Chemical class [H]N([H])C(*)=O 0.000 claims 4
- LBQVRBUQVRRHIB-UHFFFAOYSA-N 1-[[1-(1h-indol-3-yl)-2-methylpropan-2-yl]amino]-3-(2-methylphenoxy)propan-2-ol Chemical compound CC1=CC=CC=C1OCC(O)CNC(C)(C)CC1=CNC2=CC=CC=C12 LBQVRBUQVRRHIB-UHFFFAOYSA-N 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 34
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- 238000000034 method Methods 0.000 description 22
- 238000004458 analytical method Methods 0.000 description 19
- 239000000203 mixture Substances 0.000 description 19
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 13
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 13
- KFZMGEQAYNKOFK-UHFFFAOYSA-N 2-propanol Substances CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 11
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- 230000036772 blood pressure Effects 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 239000002876 beta blocker Substances 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 7
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 7
- 241000700159 Rattus Species 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000004615 ingredient Substances 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 230000003276 anti-hypertensive effect Effects 0.000 description 6
- 230000000903 blocking effect Effects 0.000 description 6
- 230000037396 body weight Effects 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 230000000304 vasodilatating effect Effects 0.000 description 6
- WREHPEFXXFJIIJ-UHFFFAOYSA-N 1-(1h-indol-3-yl)-2-methylpropan-2-amine Chemical compound C1=CC=C2C(CC(C)(N)C)=CNC2=C1 WREHPEFXXFJIIJ-UHFFFAOYSA-N 0.000 description 5
- 241000282472 Canis lupus familiaris Species 0.000 description 5
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 235000019439 ethyl acetate Nutrition 0.000 description 5
- 239000000376 reactant Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 108010010803 Gelatin Proteins 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products 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 4
- 150000007513 acids Chemical class 0.000 description 4
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- 229940039009 isoproterenol Drugs 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 4
- 238000005292 vacuum distillation Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 206010020772 Hypertension Diseases 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000001800 adrenalinergic effect Effects 0.000 description 3
- 150000001450 anions Chemical class 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropyl acetate Chemical compound CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 3
- 210000004623 platelet-rich plasma Anatomy 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000010998 test method Methods 0.000 description 3
- 230000002861 ventricular Effects 0.000 description 3
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 2
- XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 2
- 229920000945 Amylopectin Polymers 0.000 description 2
- 206010006482 Bronchospasm Diseases 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 206010011086 Coronary artery occlusion Diseases 0.000 description 2
- 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 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- MNQZXJOMYWMBOU-VKHMYHEASA-N D-glyceraldehyde Chemical compound OC[C@@H](O)C=O MNQZXJOMYWMBOU-VKHMYHEASA-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
- 208000003098 Ganglion Cysts Diseases 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical group NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 208000005400 Synovial Cyst Diseases 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000003957 anion exchange resin Substances 0.000 description 2
- 230000003288 anthiarrhythmic effect Effects 0.000 description 2
- 230000002965 anti-thrombogenic effect Effects 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 229960004042 diazoxide Drugs 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- XQYZDYMELSJDRZ-UHFFFAOYSA-N papaverine Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 XQYZDYMELSJDRZ-UHFFFAOYSA-N 0.000 description 2
- 230000010412 perfusion Effects 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
- 230000002685 pulmonary effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000005932 reductive alkylation reaction Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 229940124549 vasodilator Drugs 0.000 description 2
- 239000003071 vasodilator agent Substances 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
- MGCRGQLBPCLRSR-UHFFFAOYSA-N 1-(2-aminophenoxy)-3-[[1-(1h-indol-3-yl)-2-methylpropan-2-yl]amino]propan-2-ol;dihydrochloride Chemical compound Cl.Cl.C=1NC2=CC=CC=C2C=1CC(C)(C)NCC(O)COC1=CC=CC=C1N MGCRGQLBPCLRSR-UHFFFAOYSA-N 0.000 description 1
- IPRJVDWEEPUXCV-UHFFFAOYSA-N 1-(2-chlorophenoxy)-3-[[1-(1h-indol-3-yl)-2-methylpropan-2-yl]amino]propan-2-ol Chemical group C=1NC2=CC=CC=C2C=1CC(C)(C)NCC(O)COC1=CC=CC=C1Cl IPRJVDWEEPUXCV-UHFFFAOYSA-N 0.000 description 1
- GJNAWWLQAFCBTD-UHFFFAOYSA-N 1-(2-ethylphenoxy)-3-[[1-(1h-indol-3-yl)-2-methylpropan-2-yl]amino]propan-2-ol;hydrochloride Chemical compound Cl.CCC1=CC=CC=C1OCC(O)CNC(C)(C)CC1=CNC2=CC=CC=C12 GJNAWWLQAFCBTD-UHFFFAOYSA-N 0.000 description 1
- DBGQYBMIAWCRFB-UHFFFAOYSA-N 1-(2-fluorophenoxy)-3-[[1-(1h-indol-3-yl)-2-methylpropan-2-yl]amino]propan-2-ol;oxalic acid Chemical compound OC(=O)C(O)=O.C=1NC2=CC=CC=C2C=1CC(C)(C)NCC(O)COC1=CC=CC=C1F DBGQYBMIAWCRFB-UHFFFAOYSA-N 0.000 description 1
- FIDLEFINHDCQEC-UHFFFAOYSA-N 1-(4-chloro-2-methylphenoxy)-3-[[1-(1h-indol-3-yl)-2-methylpropan-2-yl]amino]propan-2-ol;oxalic acid Chemical compound OC(=O)C(O)=O.CC1=CC(Cl)=CC=C1OCC(O)CNC(C)(C)CC1=CNC2=CC=CC=C12 FIDLEFINHDCQEC-UHFFFAOYSA-N 0.000 description 1
- OMVNMGGHSHUHID-UHFFFAOYSA-N 1-[[1-(1H-indol-3-yl)-2-methylpropan-2-yl]amino]-3-(2-methyl-4-methylsulfonylphenoxy)propan-2-ol oxalic acid Chemical compound OC(=O)C(O)=O.CC1=CC(S(C)(=O)=O)=CC=C1OCC(O)CNC(C)(C)CC1=CNC2=CC=CC=C12 OMVNMGGHSHUHID-UHFFFAOYSA-N 0.000 description 1
- KNBOJGVVCCGMNE-UHFFFAOYSA-N 1-[[1-(1h-indol-3-yl)-2-methylpropan-2-yl]amino]-3-(2-prop-2-enylphenoxy)propan-2-ol;hydrochloride Chemical compound Cl.C=1NC2=CC=CC=C2C=1CC(C)(C)NCC(O)COC1=CC=CC=C1CC=C KNBOJGVVCCGMNE-UHFFFAOYSA-N 0.000 description 1
- HTBCZHLAEREZJE-UHFFFAOYSA-N 1-[[1-(1h-indol-3-yl)-2-methylpropan-2-yl]amino]-3-phenoxypropan-2-ol;hydrochloride Chemical compound Cl.C=1NC2=CC=CC=C2C=1CC(C)(C)NCC(O)COC1=CC=CC=C1 HTBCZHLAEREZJE-UHFFFAOYSA-N 0.000 description 1
- ZGCHLAJIRWDGFE-UHFFFAOYSA-N 1-aminopropane-1,1-diol Chemical compound CCC(N)(O)O ZGCHLAJIRWDGFE-UHFFFAOYSA-N 0.000 description 1
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
- YONLFQNRGZXBBF-UHFFFAOYSA-N 2,3-dibenzoyloxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)OC(C(O)=O)C(C(=O)O)OC(=O)C1=CC=CC=C1 YONLFQNRGZXBBF-UHFFFAOYSA-N 0.000 description 1
- IYFFPRFMOMGBGB-UHFFFAOYSA-N 2-[(2-chlorophenoxy)methyl]oxirane Chemical compound ClC1=CC=CC=C1OCC1OC1 IYFFPRFMOMGBGB-UHFFFAOYSA-N 0.000 description 1
- NCEAPFRHADKEHP-UHFFFAOYSA-N 2-[2-hydroxy-3-[[1-(1h-indol-3-yl)-2-methylpropan-2-yl]amino]propoxy]benzonitrile;hydrochloride Chemical compound Cl.C=1NC2=CC=CC=C2C=1CC(C)(C)NCC(O)COC1=CC=CC=C1C#N NCEAPFRHADKEHP-UHFFFAOYSA-N 0.000 description 1
- ISPYQTSUDJAMAB-UHFFFAOYSA-N 2-chlorophenol Chemical compound OC1=CC=CC=C1Cl ISPYQTSUDJAMAB-UHFFFAOYSA-N 0.000 description 1
- FGLBSLMDCBOPQK-UHFFFAOYSA-N 2-nitropropane Chemical compound CC(C)[N+]([O-])=O FGLBSLMDCBOPQK-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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
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- 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
- A61P9/12—Antihypertensives
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US81513877A | 1977-07-13 | 1977-07-13 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5419972A JPS5419972A (en) | 1979-02-15 |
| JPS6340784B2 true JPS6340784B2 (de) | 1988-08-12 |
Family
ID=25216976
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP8461378A Granted JPS5419972A (en) | 1977-07-13 | 1978-07-13 | 33indolylltertiary butylaminopropanols |
Country Status (30)
| Country | Link |
|---|---|
| JP (1) | JPS5419972A (de) |
| AR (1) | AR225274A1 (de) |
| AT (1) | AT364821B (de) |
| AU (1) | AU525064B2 (de) |
| BE (1) | BE868943A (de) |
| CA (1) | CA1116598A (de) |
| CH (1) | CH642066A5 (de) |
| CY (1) | CY1274A (de) |
| DE (1) | DE2830884A1 (de) |
| DK (1) | DK156568C (de) |
| ES (1) | ES471674A1 (de) |
| FI (1) | FI69835C (de) |
| FR (1) | FR2397404A1 (de) |
| GB (1) | GB2001633B (de) |
| GR (1) | GR74488B (de) |
| HK (1) | HK1385A (de) |
| HU (1) | HU178992B (de) |
| IE (1) | IE47122B1 (de) |
| IL (1) | IL55115A (de) |
| IT (1) | IT1105091B (de) |
| KE (1) | KE3485A (de) |
| LU (1) | LU79966A1 (de) |
| MY (1) | MY8500946A (de) |
| NL (1) | NL189946C (de) |
| NO (1) | NO149311C (de) |
| NZ (1) | NZ187763A (de) |
| SE (1) | SE429339B (de) |
| SG (1) | SG82584G (de) |
| YU (1) | YU40528B (de) |
| ZA (1) | ZA783744B (de) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2463765A1 (fr) * | 1979-08-17 | 1981-02-27 | Clin Midy | Nouveaux derives de l'indole actifs sur le systeme cardiovasculaire |
| US4321398A (en) * | 1981-05-07 | 1982-03-23 | Mead Johnson & Company | Thienyl and benzothienyl-tertiary butylaminophenoxypropanols |
| DE3119796A1 (de) * | 1981-05-19 | 1982-12-23 | Hoechst Ag, 6000 Frankfurt | Substituierte tryptaminderivate von thienyloxpropanolaminen, verfahren zu ihrer herstellung, pharmazeutische praeparate auf basis dieser verbindungen sowie ihre verwendung |
| FR2523964B1 (fr) * | 1982-03-23 | 1985-09-27 | Sanofi Sa | Nouveaux derives de la tryptamine actifs notamment sur le systeme cardiovasculaire et procede pour leur preparation |
| NZ208337A (en) * | 1983-06-10 | 1988-10-28 | Bristol Myers Co | 2-(2-hydroxy-3-((2-(ar-hydroxy-1h-aminopropoxy-yl)ethyl benzonitriles and pharmaceutical compositions |
| FR2601008B1 (fr) * | 1986-07-03 | 1990-03-30 | Sanofi Sa | Procede de synthese stereospecifique de derives de l'indole |
| CA2421594A1 (en) | 2000-11-10 | 2002-05-16 | John Arnold Werner | 3-substituted oxindole beta 3 agonists |
| DE60211199T2 (de) | 2001-08-14 | 2007-02-01 | Eli Lilly And Co., Indianapolis | 3-substituierte oxindol-beta-3-agonisten |
| ES2272749T3 (es) * | 2001-08-14 | 2007-05-01 | Eli Lilly And Company | Derivados de indol como agonistas beta-3 adrenergicos para el tratamiento de diabetes tipo 2. |
| JP2005518357A (ja) | 2001-11-20 | 2005-06-23 | イーライ・リリー・アンド・カンパニー | ベータ３アドレナリンアゴニスト |
| ATE297925T1 (de) | 2001-11-20 | 2005-07-15 | Lilly Co Eli | 3-substituierte oxindol beta 3 agonisten |
| US7009060B2 (en) | 2002-01-11 | 2006-03-07 | Eli Lilly And Company | 2-oxo-benzimidazolyl substituted ethanolamine derivatives and their use as β3 agonists |
| CA2960254A1 (en) | 2008-08-01 | 2010-02-04 | Arca Biopharma, Inc. | Methods and compositions involving (s)-bucindolol |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1532210A (fr) * | 1963-06-21 | 1968-07-12 | Ici Ltd | Composés hétérocycliques et leur procédé de préparation |
| CH495983A (de) * | 1968-02-09 | 1970-09-15 | Sandoz Ag | Verfahren zur Herstellung von linksdrehendem 4-(2-Hydroxy-3-isopropylaminopropoxy)indol |
| US3371098A (en) * | 1966-11-29 | 1968-02-27 | Philips Corp | 5- and 6-methoxy-3-(phenoxyethyl-aminoethyl)-indoles |
| US3946009A (en) * | 1972-05-05 | 1976-03-23 | Merck Sharp & Dohme (I.A.) Corporation | 2-(3-Substituted amino-2-hydroxypropoxy)-3-substituted pyrazines |
-
1978
- 1978-06-12 CA CA000305281A patent/CA1116598A/en not_active Expired
- 1978-06-29 ZA ZA00783744A patent/ZA783744B/xx unknown
- 1978-07-03 AU AU37704/78A patent/AU525064B2/en not_active Expired
- 1978-07-03 NZ NZ187763A patent/NZ187763A/en unknown
- 1978-07-05 YU YU1611/78A patent/YU40528B/xx unknown
- 1978-07-07 AR AR272873A patent/AR225274A1/es active
- 1978-07-10 IL IL55115A patent/IL55115A/en unknown
- 1978-07-10 SE SE7807700A patent/SE429339B/sv not_active IP Right Cessation
- 1978-07-10 FI FI782205A patent/FI69835C/fi not_active IP Right Cessation
- 1978-07-10 IT IT50228/78A patent/IT1105091B/it active
- 1978-07-10 CY CY1274A patent/CY1274A/xx unknown
- 1978-07-10 GB GB787829333A patent/GB2001633B/en not_active Expired
- 1978-07-11 NO NO782407A patent/NO149311C/no unknown
- 1978-07-11 GR GR56751A patent/GR74488B/el unknown
- 1978-07-12 IE IE1400/78A patent/IE47122B1/en not_active IP Right Cessation
- 1978-07-12 CH CH759378A patent/CH642066A5/de not_active IP Right Cessation
- 1978-07-12 DK DK313878A patent/DK156568C/da not_active IP Right Cessation
- 1978-07-12 LU LU79966A patent/LU79966A1/xx unknown
- 1978-07-12 FR FR7820851A patent/FR2397404A1/fr active Granted
- 1978-07-12 BE BE189237A patent/BE868943A/xx not_active IP Right Cessation
- 1978-07-12 HU HU78BI569A patent/HU178992B/hu unknown
- 1978-07-12 ES ES471674A patent/ES471674A1/es not_active Expired
- 1978-07-13 AT AT0508978A patent/AT364821B/de not_active IP Right Cessation
- 1978-07-13 DE DE19782830884 patent/DE2830884A1/de active Granted
- 1978-07-13 NL NLAANVRAGE7807564,A patent/NL189946C/xx not_active IP Right Cessation
- 1978-07-13 JP JP8461378A patent/JPS5419972A/ja active Granted
-
1984
- 1984-11-19 SG SG825/84A patent/SG82584G/en unknown
- 1984-12-07 KE KE3485A patent/KE3485A/xx unknown
-
1985
- 1985-01-03 HK HK13/85A patent/HK1385A/xx not_active IP Right Cessation
- 1985-12-30 MY MY946/85A patent/MY8500946A/xx unknown
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