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
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- KGPGKOSHODHUSR-UHFFFAOYSA-N 3-methyl-4-methylsulfonylphenol Chemical compound CC1=CC(O)=CC=C1S(C)(=O)=O KGPGKOSHODHUSR-UHFFFAOYSA-N 0.000 description 1
- BVRKJDJSSFTJMG-UHFFFAOYSA-N 3-tert-butyl-1,3-oxazolidin-2-one Chemical compound CC(C)(C)N1CCOC1=O BVRKJDJSSFTJMG-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 229930008281 A03AD01 - Papaverine Natural products 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- LPMXVESGRSUGHW-UHFFFAOYSA-N Acolongiflorosid K Natural products OC1C(O)C(O)C(C)OC1OC1CC2(O)CCC3C4(O)CCC(C=5COC(=O)C=5)C4(C)CC(O)C3C2(CO)C(O)C1 LPMXVESGRSUGHW-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 208000009079 Bronchial Spasm Diseases 0.000 description 1
- 208000014181 Bronchial disease Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 239000004380 Cholic acid Substances 0.000 description 1
- CGAKIHVSQWMNKH-UHFFFAOYSA-N Cl.CC1=C(OCC(C)O)C=CC=C1 Chemical compound Cl.CC1=C(OCC(C)O)C=CC=C1 CGAKIHVSQWMNKH-UHFFFAOYSA-N 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 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 1
- 206010023644 Lacrimation increased Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- LPMXVESGRSUGHW-GHYGWZAOSA-N Ouabain Natural products O([C@@H]1[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O1)[C@H]1C[C@@H](O)[C@@]2(CO)[C@@](O)(C1)CC[C@H]1[C@]3(O)[C@@](C)([C@H](C4=CC(=O)OC4)CC3)C[C@@H](O)[C@H]21 LPMXVESGRSUGHW-GHYGWZAOSA-N 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 1
- 244000166550 Strophanthus gratus Species 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 239000004004 anti-anginal agent Substances 0.000 description 1
- 230000002180 anti-stress Effects 0.000 description 1
- 229940124345 antianginal agent Drugs 0.000 description 1
- 239000003416 antiarrhythmic agent Substances 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229960004676 antithrombotic agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000008321 arterial blood flow Effects 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000007885 bronchoconstriction Effects 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 235000019416 cholic acid Nutrition 0.000 description 1
- 229960002471 cholic acid Drugs 0.000 description 1
- 230000002057 chronotropic effect Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000000625 cyclamic acid and its Na and Ca salt Substances 0.000 description 1
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
- 238000006264 debenzylation reaction Methods 0.000 description 1
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- BHBIAFSEQORUEX-UHFFFAOYSA-N ethyl acetate;2-[2-hydroxy-3-[[1-(1h-indol-3-yl)-2-methylpropan-2-yl]amino]propoxy]benzamide Chemical compound CCOC(C)=O.C=1NC2=CC=CC=C2C=1CC(C)(C)NCC(O)COC1=CC=CC=C1C(N)=O BHBIAFSEQORUEX-UHFFFAOYSA-N 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000003944 halohydrins Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- AKPUJVVHYUHGKY-UHFFFAOYSA-N hydron;propan-2-ol;chloride Chemical compound Cl.CC(C)O AKPUJVVHYUHGKY-UHFFFAOYSA-N 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000000297 inotrophic effect Effects 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229940045996 isethionic acid Drugs 0.000 description 1
- 229940011051 isopropyl acetate Drugs 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 239000004922 lacquer Substances 0.000 description 1
- 230000004317 lacrimation Effects 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000005649 metathesis reaction Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- LPMXVESGRSUGHW-HBYQJFLCSA-N ouabain Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]1C[C@@]2(O)CC[C@H]3[C@@]4(O)CC[C@H](C=5COC(=O)C=5)[C@@]4(C)C[C@@H](O)[C@@H]3[C@@]2(CO)[C@H](O)C1 LPMXVESGRSUGHW-HBYQJFLCSA-N 0.000 description 1
- 229960003343 ouabain Drugs 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 150000002924 oxiranes Chemical class 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229960001789 papaverine Drugs 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036581 peripheral resistance Effects 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- UBYZGUWQNIEQMH-SBBOJQDXSA-M potassium;(2s,3s,4s,5r)-2,3,4,5,6-pentahydroxy-6-oxohexanoate Chemical compound [K+].OC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O UBYZGUWQNIEQMH-SBBOJQDXSA-M 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 229960003712 propranolol Drugs 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- ZBMZVLHSJCTVON-UHFFFAOYSA-N sotalol Chemical compound CC(C)NCC(O)C1=CC=C(NS(C)(=O)=O)C=C1 ZBMZVLHSJCTVON-UHFFFAOYSA-N 0.000 description 1
- 229960002370 sotalol Drugs 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 230000002885 thrombogenetic effect Effects 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 235000010215 titanium dioxide Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
Classifications
-
- 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
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Neurology (AREA)
- Hematology (AREA)
- Hospice & Palliative Care (AREA)
- Biomedical Technology (AREA)
- Diabetes (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
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 (xx) | 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 (xx) |
AR (1) | AR225274A1 (xx) |
AT (1) | AT364821B (xx) |
AU (1) | AU525064B2 (xx) |
BE (1) | BE868943A (xx) |
CA (1) | CA1116598A (xx) |
CH (1) | CH642066A5 (xx) |
CY (1) | CY1274A (xx) |
DE (1) | DE2830884A1 (xx) |
DK (1) | DK156568C (xx) |
ES (1) | ES471674A1 (xx) |
FI (1) | FI69835C (xx) |
FR (1) | FR2397404A1 (xx) |
GB (1) | GB2001633B (xx) |
GR (1) | GR74488B (xx) |
HK (1) | HK1385A (xx) |
HU (1) | HU178992B (xx) |
IE (1) | IE47122B1 (xx) |
IL (1) | IL55115A (xx) |
IT (1) | IT1105091B (xx) |
KE (1) | KE3485A (xx) |
LU (1) | LU79966A1 (xx) |
MY (1) | MY8500946A (xx) |
NL (1) | NL189946C (xx) |
NO (1) | NO149311C (xx) |
NZ (1) | NZ187763A (xx) |
SE (1) | SE429339B (xx) |
SG (1) | SG82584G (xx) |
YU (1) | YU40528B (xx) |
ZA (1) | ZA783744B (xx) |
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 |
DE60120748T2 (de) | 2000-11-10 | 2007-05-16 | Eli Lilly And Co., Indianapolis | 3-substituierte oxindolderivate als beta-3-agonisten |
DE60215028T2 (de) | 2001-08-14 | 2007-03-15 | Eli Lilly And Co., Indianapolis | Indol derivate als beta-3-adrenerge agonisten zur behandlung von typ 2 diabetes |
ATE325119T1 (de) | 2001-08-14 | 2006-06-15 | Lilly Co Eli | 3-substituierte oxindol-beta-3-agonisten |
WO2003044016A1 (en) | 2001-11-20 | 2003-05-30 | Eli Lilly And Company | 3-SUBSTITUTED OXINDOLE β3 AGONISTS |
EP1448561B1 (en) | 2001-11-20 | 2008-02-20 | Eli Lilly And Company | Beta 3 adrenergic agonists |
JP2005520805A (ja) | 2002-01-11 | 2005-07-14 | イーライ・リリー・アンド・カンパニー | 2−オキソ−ベンズイミダゾリル置換型エタノールアミン誘導体およびβ3アゴニストとしてのその使用 |
US8946284B2 (en) | 2008-08-01 | 2015-02-03 | 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 NZ NZ187763A patent/NZ187763A/en unknown
- 1978-07-03 AU AU37704/78A patent/AU525064B2/en not_active Expired
- 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 IT IT50228/78A patent/IT1105091B/it active
- 1978-07-10 GB GB787829333A patent/GB2001633B/en not_active Expired
- 1978-07-10 FI FI782205A patent/FI69835C/fi not_active IP Right Cessation
- 1978-07-10 CY CY1274A patent/CY1274A/xx unknown
- 1978-07-10 SE SE7807700A patent/SE429339B/sv not_active IP Right Cessation
- 1978-07-11 GR GR56751A patent/GR74488B/el unknown
- 1978-07-11 NO NO782407A patent/NO149311C/no unknown
- 1978-07-12 LU LU79966A patent/LU79966A1/xx unknown
- 1978-07-12 CH CH759378A patent/CH642066A5/de not_active IP Right Cessation
- 1978-07-12 FR FR7820851A patent/FR2397404A1/fr active Granted
- 1978-07-12 ES ES471674A patent/ES471674A1/es not_active Expired
- 1978-07-12 BE BE189237A patent/BE868943A/xx not_active IP Right Cessation
- 1978-07-12 IE IE1400/78A patent/IE47122B1/en not_active IP Right Cessation
- 1978-07-12 DK DK313878A patent/DK156568C/da not_active IP Right Cessation
- 1978-07-12 HU HU78BI569A patent/HU178992B/hu unknown
- 1978-07-13 JP JP8461378A patent/JPS5419972A/ja active Granted
- 1978-07-13 AT AT0508978A patent/AT364821B/de not_active IP Right Cessation
- 1978-07-13 NL NLAANVRAGE7807564,A patent/NL189946C/xx not_active IP Right Cessation
- 1978-07-13 DE DE19782830884 patent/DE2830884A1/de 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
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US4234595A (en) | 3-Indolyl-tertiary butylaminopropanols | |
EP0125783B1 (en) | Dopamine-beta-hydroxylase inhibitors | |
JPS6354321A (ja) | 血糖降下剤 | |
CA1213280A (fr) | PROCEDE DE PREPARATION DE NOUVEAUX DERIVES DE 4-(1H- INDOL-3-YL) .alpha.-METHYL PIPERIDINE-1-ETHANOL ET DE LEURS SELS | |
JPS6340784B2 (xx) | ||
CZ397598A3 (cs) | Derivát 5-fenoxyalkyl-2,4-thiazolidindionu, způsob jeho přípravy, meziprodukty pro jeho přípravu a farmaceutický prostředek, který ho obsahuje | |
JPH0819057B2 (ja) | 新規なフェニルプロピニルアミン誘導体の製造法 | |
US4314943A (en) | Heterocyclic substituted aryloxy 3-indolyl-tertiary butylaminopropanols | |
JP5486008B2 (ja) | 1‐ブチル‐2‐ヒドロキシアラルキルピペラジン誘導体およびその抗鬱剤としての使用 | |
JPS6334865B2 (xx) | ||
JPS6257606B2 (xx) | ||
JPS63255258A (ja) | N−フェネチルアミノアルキル−ベンズアミド抗不整脈剤 | |
US4000192A (en) | Pharmacologically active compounds | |
JP2001503753A (ja) | アリールオキシプロパノールアミン誘導体、その製造方法及びその用途 | |
JPH034073B2 (xx) | ||
US3959476A (en) | Antihypertensive substituted triazoles | |
GB2074576A (en) | 1-(acylamino-aryloxy)-3-alkylamino-propan-2-ols processes for their preparation and pharmaceutical compositions containing them | |
US4338319A (en) | Method for the treatment of chronic obstructive airway or cardiac diseases | |
KR820001447B1 (ko) | 3-인돌릴-3급 부틸아미노프로판올의 제조방법 | |
EP0260814B1 (en) | Dopamine-beta-hydroxylase inhibitors | |
JPS584026B2 (ja) | ピラジンユウドウタイ オヨビ セイホウ | |
JPS6410512B2 (xx) | ||
US4495352A (en) | Heterocyclic substituted aryloxy 3-indolyl-tertiary butylaminopropanols | |
KR900005021B1 (ko) | 1-펜옥시-3-히드록시 인돌릴 알킬아미노-3-프로판올류 및 그 제조방법 | |
JP2989059B2 (ja) | 置換アニリド |