JPH0587503B2 - - Google Patents
Info
- Publication number
- JPH0587503B2 JPH0587503B2 JP59116767A JP11676784A JPH0587503B2 JP H0587503 B2 JPH0587503 B2 JP H0587503B2 JP 59116767 A JP59116767 A JP 59116767A JP 11676784 A JP11676784 A JP 11676784A JP H0587503 B2 JPH0587503 B2 JP H0587503B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- hydroxy
- compound
- hydrogen
- indole ring
- 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 - Fee Related
Links
- 150000001875 compounds Chemical class 0.000 claims description 51
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 32
- 238000000034 method Methods 0.000 claims description 31
- -1 methoxylated indole alkylamine Chemical class 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 14
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 125000001041 indolyl group Chemical group 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 6
- 230000008878 coupling Effects 0.000 claims description 5
- 238000010168 coupling process Methods 0.000 claims description 5
- 238000005859 coupling reaction Methods 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- IUKUBLQOWNHWPE-UHFFFAOYSA-N 2-[2-hydroxy-3-[[1-(6-hydroxy-1h-indol-3-yl)-2-methylpropan-2-yl]amino]propoxy]benzonitrile Chemical compound C=1NC2=CC(O)=CC=C2C=1CC(C)(C)NCC(O)COC1=CC=CC=C1C#N IUKUBLQOWNHWPE-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- RLHZDXDBSDXXNX-UHFFFAOYSA-N 2-[2-hydroxy-3-[[1-(5-hydroxy-1h-indol-3-yl)-2-methylpropan-2-yl]amino]propoxy]benzonitrile Chemical compound C=1NC2=CC=C(O)C=C2C=1CC(C)(C)NCC(O)COC1=CC=CC=C1C#N RLHZDXDBSDXXNX-UHFFFAOYSA-N 0.000 claims 1
- 125000004103 aminoalkyl group Chemical group 0.000 claims 1
- 238000010561 standard procedure Methods 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 45
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 34
- 239000000203 mixture Substances 0.000 description 27
- 239000000243 solution Substances 0.000 description 26
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 239000000047 product Substances 0.000 description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 18
- 239000000543 intermediate Substances 0.000 description 18
- 238000010992 reflux Methods 0.000 description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- 239000007787 solid Substances 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- 238000003756 stirring Methods 0.000 description 10
- 241000700159 Rattus Species 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- 235000019198 oils Nutrition 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 239000002220 antihypertensive agent Substances 0.000 description 8
- 229940030600 antihypertensive agent Drugs 0.000 description 8
- 230000036772 blood pressure Effects 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 239000007788 liquid Substances 0.000 description 7
- 239000012280 lithium aluminium hydride Substances 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 6
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical group C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- FBMYKMYQHCBIGU-UHFFFAOYSA-N 2-[2-hydroxy-3-[[1-(1h-indol-3-yl)-2-methylpropan-2-yl]amino]propoxy]benzonitrile Chemical compound C=1NC2=CC=CC=C2C=1CC(C)(C)NCC(O)COC1=CC=CC=C1C#N FBMYKMYQHCBIGU-UHFFFAOYSA-N 0.000 description 5
- IKCZUPRWPVLSLF-UHFFFAOYSA-N 2-methoxy-1h-indole Chemical compound C1=CC=C2NC(OC)=CC2=C1 IKCZUPRWPVLSLF-UHFFFAOYSA-N 0.000 description 5
- 239000004593 Epoxy Substances 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 5
- 230000003276 anti-hypertensive effect Effects 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- VPGRYOFKCNULNK-ACXQXYJUSA-N Deoxycorticosterone acetate Chemical class C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)COC(=O)C)[C@@]1(C)CC2 VPGRYOFKCNULNK-ACXQXYJUSA-N 0.000 description 4
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
- 206010020772 Hypertension Diseases 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 235000011054 acetic acid Nutrition 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 4
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 4
- 229950005341 bucindolol Drugs 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 150000002431 hydrogen Chemical class 0.000 description 4
- 238000005805 hydroxylation reaction Methods 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 239000008188 pellet Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- SMQUZDBALVYZAC-UHFFFAOYSA-N salicylaldehyde Chemical class OC1=CC=CC=C1C=O SMQUZDBALVYZAC-UHFFFAOYSA-N 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000006188 syrup Substances 0.000 description 4
- 235000020357 syrup Nutrition 0.000 description 4
- 229940124549 vasodilator Drugs 0.000 description 4
- 239000003071 vasodilator agent Substances 0.000 description 4
- ODFSNCWVKJJXJQ-UHFFFAOYSA-N 2-(1H-indol-2-yl)-N-methoxyethanamine Chemical compound CONCCC=1NC2=CC=CC=C2C1 ODFSNCWVKJJXJQ-UHFFFAOYSA-N 0.000 description 3
- CHZCERSEMVWNHL-UHFFFAOYSA-N 2-hydroxybenzonitrile Chemical class OC1=CC=CC=C1C#N CHZCERSEMVWNHL-UHFFFAOYSA-N 0.000 description 3
- SXZPHYCOZQEYEV-UHFFFAOYSA-N 2-methoxy-1h-indole-3-carbaldehyde Chemical compound C1=CC=C2C(C=O)=C(OC)NC2=C1 SXZPHYCOZQEYEV-UHFFFAOYSA-N 0.000 description 3
- FGLBSLMDCBOPQK-UHFFFAOYSA-N 2-nitropropane Chemical compound CC(C)[N+]([O-])=O FGLBSLMDCBOPQK-UHFFFAOYSA-N 0.000 description 3
- CWUHFFCMFYWBIO-UHFFFAOYSA-N 3-methoxy-1h-indole-2-carbaldehyde Chemical compound C1=CC=C2C(OC)=C(C=O)NC2=C1 CWUHFFCMFYWBIO-UHFFFAOYSA-N 0.000 description 3
- 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 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 3
- 239000005695 Ammonium acetate Substances 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 208000003098 Ganglion Cysts Diseases 0.000 description 3
- NAGJBCQMVPOMEO-UHFFFAOYSA-N N-tert-butyl-6-methoxy-1H-indol-3-amine Chemical compound COC1=CC=C2C(=CNC2=C1)NC(C)(C)C NAGJBCQMVPOMEO-UHFFFAOYSA-N 0.000 description 3
- VYLPAKJWZRQJBP-UHFFFAOYSA-N N-tert-butyl-N-methoxy-1H-indol-2-amine Chemical compound CON(C(C)(C)C)C=1NC2=CC=CC=C2C1 VYLPAKJWZRQJBP-UHFFFAOYSA-N 0.000 description 3
- 239000007868 Raney catalyst Chemical class 0.000 description 3
- 229910000564 Raney nickel Chemical class 0.000 description 3
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical class [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 3
- 208000005400 Synovial Cyst Diseases 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 229940043376 ammonium acetate Drugs 0.000 description 3
- 235000019257 ammonium acetate Nutrition 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000007900 aqueous suspension Substances 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000012259 ether extract Substances 0.000 description 3
- 230000001631 hypertensive effect Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 230000000304 vasodilatating effect Effects 0.000 description 3
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 2
- GOERTRUXQHDLHC-UHFFFAOYSA-N 1-(5-methoxy-1h-indol-3-yl)-n,n-dimethylmethanamine Chemical compound COC1=CC=C2NC=C(CN(C)C)C2=C1 GOERTRUXQHDLHC-UHFFFAOYSA-N 0.000 description 2
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 2
- XEEANGGQJOWRTG-UHFFFAOYSA-N 1h-indol-2-ylmethanol Chemical class C1=CC=C2NC(CO)=CC2=C1 XEEANGGQJOWRTG-UHFFFAOYSA-N 0.000 description 2
- BIJYXIOVXFBJEP-UHFFFAOYSA-N 2-(oxiran-2-ylmethoxy)benzonitrile Chemical compound N#CC1=CC=CC=C1OCC1OC1 BIJYXIOVXFBJEP-UHFFFAOYSA-N 0.000 description 2
- QJRWYBIKLXNYLF-UHFFFAOYSA-N 6-methoxy-1h-indole Chemical compound COC1=CC=C2C=CNC2=C1 QJRWYBIKLXNYLF-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- PJUKHNJSTCXFFT-UHFFFAOYSA-N N-tert-butyl-N-methoxy-1H-indol-3-amine Chemical compound CON(C(C)(C)C)C1=CNC2=CC=CC=C12 PJUKHNJSTCXFFT-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 238000007013 Reimer-Tiemann formylation reaction Methods 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 239000002876 beta blocker Substances 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 238000012925 biological evaluation Methods 0.000 description 2
- 238000009530 blood pressure measurement Methods 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 235000008504 concentrate Nutrition 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- GKIPXFAANLTWBM-UHFFFAOYSA-N epibromohydrin Chemical compound BrCC1CO1 GKIPXFAANLTWBM-UHFFFAOYSA-N 0.000 description 2
- WDCDAAMJNUHOIY-UHFFFAOYSA-N ethyl acetate;2-propan-2-yloxypropane Chemical compound CCOC(C)=O.CC(C)OC(C)C WDCDAAMJNUHOIY-UHFFFAOYSA-N 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000007429 general method Methods 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 2
- 150000003840 hydrochlorides Chemical class 0.000 description 2
- 150000002475 indoles Chemical class 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000013067 intermediate product Substances 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- 229940039009 isoproterenol Drugs 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 230000037353 metabolic pathway Effects 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- 150000002924 oxiranes Chemical class 0.000 description 2
- NWVVVBRKAWDGAB-UHFFFAOYSA-N p-methoxyphenol Chemical compound COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 description 2
- 150000002989 phenols Chemical class 0.000 description 2
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 2
- 229960001802 phenylephrine Drugs 0.000 description 2
- XTUSEBKMEQERQV-UHFFFAOYSA-N propan-2-ol;hydrate Chemical compound O.CC(C)O XTUSEBKMEQERQV-UHFFFAOYSA-N 0.000 description 2
- 229960003712 propranolol Drugs 0.000 description 2
- 238000011552 rat model Methods 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 230000003595 spectral effect Effects 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 230000035488 systolic blood pressure Effects 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
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- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000001975 sympathomimetic effect Effects 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- APJYDQYYACXCRM-UHFFFAOYSA-O tryptaminium Chemical compound C1=CC=C2C(CC[NH3+])=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-O 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 210000001186 vagus nerve Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 238000005303 weighing Methods 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/12—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
- C07D303/18—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by etherified hydroxyl radicals
- C07D303/20—Ethers with hydroxy compounds containing no oxirane rings
- C07D303/22—Ethers with hydroxy compounds containing no oxirane rings with monohydroxy compounds
-
- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
-
- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Indole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US50290183A | 1983-06-10 | 1983-06-10 | |
| US502901 | 1983-06-10 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS608262A JPS608262A (ja) | 1985-01-17 |
| JPH0587503B2 true JPH0587503B2 (it) | 1993-12-16 |
Family
ID=23999880
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP59116767A Granted JPS608262A (ja) | 1983-06-10 | 1984-06-08 | １−フエノキシ−３−ヒドロキシインドリル−アルキルアミノ−３−プロパノ−ル類及びその製法 |
Country Status (29)
| Country | Link |
|---|---|
| JP (1) | JPS608262A (it) |
| KR (1) | KR900005021B1 (it) |
| AT (1) | AT381492B (it) |
| AU (1) | AU569303B2 (it) |
| BE (1) | BE899875A (it) |
| CA (1) | CA1217496A (it) |
| CH (1) | CH662561A5 (it) |
| CY (1) | CY1518A (it) |
| DE (1) | DE3421252A1 (it) |
| DK (1) | DK162089C (it) |
| ES (1) | ES8507490A1 (it) |
| FI (1) | FI78291C (it) |
| FR (1) | FR2549054B1 (it) |
| GB (1) | GB2141121B (it) |
| GR (1) | GR82208B (it) |
| HK (1) | HK14690A (it) |
| HU (1) | HU191670B (it) |
| IE (1) | IE57682B1 (it) |
| IL (1) | IL72008A (it) |
| IT (1) | IT1206705B (it) |
| LU (1) | LU85410A1 (it) |
| MY (1) | MY102077A (it) |
| NL (1) | NL8401840A (it) |
| NO (1) | NO164471C (it) |
| NZ (1) | NZ208337A (it) |
| SE (1) | SE455865B (it) |
| SG (1) | SG1090G (it) |
| YU (1) | YU44873B (it) |
| ZA (1) | ZA844277B (it) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2601008B1 (fr) * | 1986-07-03 | 1990-03-30 | Sanofi Sa | Procede de synthese stereospecifique de derives de l'indole |
| KR101986648B1 (ko) | 2018-04-06 | 2019-06-07 | (유)로뎀건설 | 강관작업구 굴착장치 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB962793A (en) * | 1959-07-13 | 1964-07-01 | Philips Nv | Improvements in or relating to pharmacologically active compounds being substituted tryptamines |
| NL300886A (it) * | 1962-11-23 | |||
| US4314943A (en) * | 1977-07-13 | 1982-02-09 | Mead Johnson & Company | Heterocyclic substituted aryloxy 3-indolyl-tertiary butylaminopropanols |
| CA1116598A (en) * | 1977-07-13 | 1982-01-19 | William T. Comer | 3-indolyl-tertiary butylaminopropanols |
| US4234595A (en) * | 1977-07-13 | 1980-11-18 | Mead Johnson & Company | 3-Indolyl-tertiary butylaminopropanols |
| FR2463765A1 (fr) * | 1979-08-17 | 1981-02-27 | Clin Midy | Nouveaux derives de l'indole actifs sur le systeme cardiovasculaire |
-
1984
- 1984-05-31 NZ NZ208337A patent/NZ208337A/xx unknown
- 1984-06-04 IL IL72008A patent/IL72008A/xx unknown
- 1984-06-06 FR FR8408858A patent/FR2549054B1/fr not_active Expired
- 1984-06-06 AT AT0186784A patent/AT381492B/de not_active IP Right Cessation
- 1984-06-06 ES ES533185A patent/ES8507490A1/es not_active Expired
- 1984-06-06 ZA ZA844277A patent/ZA844277B/xx unknown
- 1984-06-06 NO NO842279A patent/NO164471C/no unknown
- 1984-06-07 YU YU997/84A patent/YU44873B/xx unknown
- 1984-06-07 GR GR74949A patent/GR82208B/el unknown
- 1984-06-07 FI FI842316A patent/FI78291C/fi not_active IP Right Cessation
- 1984-06-07 DE DE19843421252 patent/DE3421252A1/de not_active Ceased
- 1984-06-08 BE BE0/213109A patent/BE899875A/fr not_active IP Right Cessation
- 1984-06-08 SE SE8403112A patent/SE455865B/sv not_active IP Right Cessation
- 1984-06-08 DK DK284184A patent/DK162089C/da not_active IP Right Cessation
- 1984-06-08 NL NL8401840A patent/NL8401840A/nl active Search and Examination
- 1984-06-08 IE IE1441/84A patent/IE57682B1/en not_active IP Right Cessation
- 1984-06-08 IT IT8421330A patent/IT1206705B/it active
- 1984-06-08 AU AU29238/84A patent/AU569303B2/en not_active Ceased
- 1984-06-08 CA CA000456154A patent/CA1217496A/en not_active Expired
- 1984-06-08 CH CH2814/84A patent/CH662561A5/de not_active IP Right Cessation
- 1984-06-08 LU LU85410A patent/LU85410A1/fr unknown
- 1984-06-08 GB GB08414652A patent/GB2141121B/en not_active Expired
- 1984-06-08 JP JP59116767A patent/JPS608262A/ja active Granted
- 1984-06-08 HU HU842215A patent/HU191670B/hu not_active IP Right Cessation
- 1984-06-09 KR KR1019840003251A patent/KR900005021B1/ko not_active IP Right Cessation
-
1987
- 1987-09-29 MY MYPI87002203A patent/MY102077A/en unknown
-
1990
- 1990-01-08 SG SG10/90A patent/SG1090G/en unknown
- 1990-02-22 HK HK146/90A patent/HK14690A/xx not_active IP Right Cessation
- 1990-11-16 CY CY1518A patent/CY1518A/xx unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| LAPS | Cancellation because of no payment of annual fees |