DE2737630C2 - - Google Patents
Info
- Publication number
- DE2737630C2 DE2737630C2 DE19772737630 DE2737630A DE2737630C2 DE 2737630 C2 DE2737630 C2 DE 2737630C2 DE 19772737630 DE19772737630 DE 19772737630 DE 2737630 A DE2737630 A DE 2737630A DE 2737630 C2 DE2737630 C2 DE 2737630C2
- Authority
- DE
- Germany
- Prior art keywords
- group
- general formula
- compound
- propoxy
- hydroxy
- 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 39
- 150000003839 salts Chemical class 0.000 claims description 11
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 125000006239 protecting group Chemical group 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 6
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 6
- 125000001041 indolyl group Chemical group 0.000 claims description 5
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 150000002431 hydrogen Chemical group 0.000 claims description 3
- 150000002473 indoazoles Chemical class 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 150000003254 radicals Chemical class 0.000 claims description 3
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 2
- MXZROAOUCUVNHX-UHFFFAOYSA-N 2-Aminopropanol Chemical class CCC(N)O MXZROAOUCUVNHX-UHFFFAOYSA-N 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 239000000203 mixture Substances 0.000 description 21
- -1 methoxy, Ethoxy, propoxy, butoxy Chemical group 0.000 description 16
- 239000000243 solution Substances 0.000 description 16
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 12
- 239000013078 crystal Substances 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- BREBKAKBNYXIOP-UHFFFAOYSA-N 4-(phenoxymethyl)piperidine Chemical compound C1CNCCC1COC1=CC=CC=C1 BREBKAKBNYXIOP-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000003921 oil Substances 0.000 description 7
- 235000019198 oils Nutrition 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 6
- 235000011181 potassium carbonates Nutrition 0.000 description 6
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 6
- 239000012071 phase Substances 0.000 description 5
- ARFNSMYWLYZEPU-UHFFFAOYSA-N 1-(1h-indol-4-yloxy)-3-[4-(phenoxymethyl)piperidin-1-yl]propan-2-ol Chemical compound C=1C=CC=2NC=CC=2C=1OCC(O)CN(CC1)CCC1COC1=CC=CC=C1 ARFNSMYWLYZEPU-UHFFFAOYSA-N 0.000 description 4
- FUWVFGJQAVUIFN-UHFFFAOYSA-N 3-[3-[4-(phenoxymethyl)piperidin-1-yl]propoxy]benzene-1,2-diamine;trihydrochloride Chemical compound Cl.Cl.Cl.NC1=CC=CC(OCCCN2CCC(COC=3C=CC=CC=3)CC2)=C1N FUWVFGJQAVUIFN-UHFFFAOYSA-N 0.000 description 4
- 239000005711 Benzoic acid Substances 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- 239000007868 Raney catalyst Substances 0.000 description 4
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
- 229910000564 Raney nickel Inorganic materials 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 235000010233 benzoic acid Nutrition 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- LRJIACGZPACLFS-UHFFFAOYSA-N 2-benzyl-7-methyl-4-(oxiran-2-ylmethoxy)indazole Chemical compound C12=CN(CC=3C=CC=CC=3)N=C2C(C)=CC=C1OCC1CO1 LRJIACGZPACLFS-UHFFFAOYSA-N 0.000 description 3
- KMRIUKNMUKDUCJ-UHFFFAOYSA-N 2-nitro-6-[3-[4-(phenoxymethyl)piperidin-1-yl]propoxy]aniline;hydrochloride Chemical compound Cl.C1=CC=C([N+]([O-])=O)C(N)=C1OCCCN1CCC(COC=2C=CC=CC=2)CC1 KMRIUKNMUKDUCJ-UHFFFAOYSA-N 0.000 description 3
- ZTVNNUONPBNKHV-UHFFFAOYSA-N 3-(2-benzylindazol-4-yl)oxypropyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCCCOC(C1=C2)=CC=CC1=NN2CC1=CC=CC=C1 ZTVNNUONPBNKHV-UHFFFAOYSA-N 0.000 description 3
- CTWQPSSVUYPWOM-UHFFFAOYSA-N 4-(oxiran-2-ylmethoxy)-1h-indole Chemical compound C=1C=CC=2NC=CC=2C=1OCC1CO1 CTWQPSSVUYPWOM-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 3
- 229940073608 benzyl chloride Drugs 0.000 description 3
- 239000003054 catalyst 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
- 239000012141 concentrate Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- MOYSKNAMCCSLAO-UHFFFAOYSA-N 1-(1h-indazol-4-yloxy)-3-[4-(phenoxymethyl)piperidin-1-yl]propan-2-ol Chemical compound C=1C=CC=2NN=CC=2C=1OCC(O)CN(CC1)CCC1COC1=CC=CC=C1 MOYSKNAMCCSLAO-UHFFFAOYSA-N 0.000 description 2
- BEPZGBDTTOZVTR-UHFFFAOYSA-N 1-(2,3-diaminophenoxy)-3-[4-(phenoxymethyl)piperidin-1-yl]propan-2-ol;trihydrochloride Chemical compound Cl.Cl.Cl.NC1=CC=CC(OCC(O)CN2CCC(COC=3C=CC=CC=3)CC2)=C1N BEPZGBDTTOZVTR-UHFFFAOYSA-N 0.000 description 2
- OHIFCYWGLKGPNX-UHFFFAOYSA-N 1-[[2-(hydroxymethyl)-1h-indol-4-yl]oxy]-3-[4-(phenoxymethyl)piperidin-1-yl]propan-2-ol Chemical compound C1=CC=C2NC(CO)=CC2=C1OCC(O)CN(CC1)CCC1COC1=CC=CC=C1 OHIFCYWGLKGPNX-UHFFFAOYSA-N 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- KIBXUXDCTYYPQG-UHFFFAOYSA-N 2-benzylindazol-4-ol Chemical compound C1=C2C(O)=CC=CC2=NN1CC1=CC=CC=C1 KIBXUXDCTYYPQG-UHFFFAOYSA-N 0.000 description 2
- WQAFOHJDMDYCPB-UHFFFAOYSA-N 3-(2-benzylindazol-4-yl)oxypropan-1-ol Chemical compound C1=C2C(OCCCO)=CC=CC2=NN1CC1=CC=CC=C1 WQAFOHJDMDYCPB-UHFFFAOYSA-N 0.000 description 2
- HCRAKLHPODRHQA-UHFFFAOYSA-N 4-[3-[4-(phenoxymethyl)piperidin-1-yl]propoxy]-1h-indole Chemical compound C=1C=CC=2NC=CC=2C=1OCCCN(CC1)CCC1COC1=CC=CC=C1 HCRAKLHPODRHQA-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 2
- YPYSERZXQBYPNJ-UHFFFAOYSA-N ethyl 4-[2-hydroxy-3-[4-(phenoxymethyl)piperidin-1-yl]propoxy]-1h-indole-2-carboxylate Chemical compound C1=CC=C2NC(C(=O)OCC)=CC2=C1OCC(O)CN(CC1)CCC1COC1=CC=CC=C1 YPYSERZXQBYPNJ-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229920006158 high molecular weight polymer Polymers 0.000 description 2
- 238000007327 hydrogenolysis reaction Methods 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
- OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 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
- 238000004519 manufacturing process Methods 0.000 description 2
- 229910052987 metal hydride Inorganic materials 0.000 description 2
- 150000004681 metal hydrides Chemical class 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 230000009935 nitrosation Effects 0.000 description 2
- 238000007034 nitrosation reaction Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 2
- 229910003446 platinum oxide Inorganic materials 0.000 description 2
- 239000010970 precious metal Substances 0.000 description 2
- 238000006798 ring closing metathesis reaction Methods 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- WUULVHDYJZRZPZ-UHFFFAOYSA-N 1-(2h-benzotriazol-4-yloxy)-3-[4-(phenoxymethyl)piperidin-1-yl]propan-2-ol Chemical compound C=1C=CC=2NN=NC=2C=1OCC(O)CN(CC1)CCC1COC1=CC=CC=C1 WUULVHDYJZRZPZ-UHFFFAOYSA-N 0.000 description 1
- PFOVRLZFVUZAAA-UHFFFAOYSA-N 1-(2h-benzotriazol-4-yloxy)-3-[4-(phenoxymethyl)piperidin-1-yl]propan-2-ol;hydrochloride Chemical compound Cl.C=1C=CC=2NN=NC=2C=1OCC(O)CN(CC1)CCC1COC1=CC=CC=C1 PFOVRLZFVUZAAA-UHFFFAOYSA-N 0.000 description 1
- WBAXSQUIGRIDCS-UHFFFAOYSA-N 1-(oxiran-2-ylmethyl)-4-(phenoxymethyl)piperidine Chemical compound C1CN(CC2OC2)CCC1COC1=CC=CC=C1 WBAXSQUIGRIDCS-UHFFFAOYSA-N 0.000 description 1
- RFIQLGKXBMUYIK-UHFFFAOYSA-N 1-[(2-methyl-1h-indol-4-yl)oxy]-3-[4-(phenoxymethyl)piperidin-1-yl]propan-2-ol Chemical compound C1=CC=C2NC(C)=CC2=C1OCC(O)CN(CC1)CCC1COC1=CC=CC=C1 RFIQLGKXBMUYIK-UHFFFAOYSA-N 0.000 description 1
- XSMMUYJGFJFZJV-UHFFFAOYSA-N 1-[(6-tert-butyl-1h-indazol-4-yl)oxy]-3-[4-(phenoxymethyl)piperidin-1-yl]propan-2-ol Chemical compound C=12C=NNC2=CC(C(C)(C)C)=CC=1OCC(O)CN(CC1)CCC1COC1=CC=CC=C1 XSMMUYJGFJFZJV-UHFFFAOYSA-N 0.000 description 1
- JNLRNFUAFLKPHK-UHFFFAOYSA-N 1-[(7-methyl-1h-indazol-4-yl)oxy]-3-[4-(phenoxymethyl)piperidin-1-yl]propan-2-ol Chemical compound C1=2C=NNC=2C(C)=CC=C1OCC(O)CN(CC1)CCC1COC1=CC=CC=C1 JNLRNFUAFLKPHK-UHFFFAOYSA-N 0.000 description 1
- IURLBGBKXFKMQR-UHFFFAOYSA-N 1-[6-tert-butyl-4-(oxiran-2-ylmethoxy)indazol-1-yl]ethanone Chemical compound C1=C(C(C)(C)C)C=C2N(C(=O)C)N=CC2=C1OCC1CO1 IURLBGBKXFKMQR-UHFFFAOYSA-N 0.000 description 1
- VEHIDRGRVXLWAY-UHFFFAOYSA-N 1-[[(2,4-dimethyl-3-nitrophenyl)-phenylmethoxy]-phenylmethyl]-2,4-dimethyl-3-nitrobenzene Chemical compound CC1=C([N+]([O-])=O)C(C)=CC=C1C(C=1C=CC=CC=1)OC(C=1C(=C(C(C)=CC=1)[N+]([O-])=O)C)C1=CC=CC=C1 VEHIDRGRVXLWAY-UHFFFAOYSA-N 0.000 description 1
- NMGLVHXJOMBIJW-UHFFFAOYSA-N 1h-benzimidazole;dihydrochloride Chemical compound Cl.Cl.C1=CC=C2NC=NC2=C1 NMGLVHXJOMBIJW-UHFFFAOYSA-N 0.000 description 1
- PBXYRJKKBWMVSG-UHFFFAOYSA-N 2,4-dimethyl-3-nitrophenol Chemical compound CC1=CC=C(O)C(C)=C1[N+]([O-])=O PBXYRJKKBWMVSG-UHFFFAOYSA-N 0.000 description 1
- JNQPINGKMBCWMD-UHFFFAOYSA-N 2-(3-chloropropoxy)-6-nitroaniline Chemical compound NC1=C(OCCCCl)C=CC=C1[N+]([O-])=O JNQPINGKMBCWMD-UHFFFAOYSA-N 0.000 description 1
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- 230000003000 nontoxic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
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- NOQXXYIGRPAZJC-UHFFFAOYSA-N oxiran-2-ylmethyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC1OC1 NOQXXYIGRPAZJC-UHFFFAOYSA-N 0.000 description 1
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- 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
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- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
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- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
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- 239000008117 stearic acid Substances 0.000 description 1
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- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Priority Applications (41)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19772737630 DE2737630A1 (de) | 1977-08-20 | 1977-08-20 | Neue aminopropanolderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| US05/846,057 US4146630A (en) | 1976-11-12 | 1977-10-27 | Blood pressure lowering and adrenergic β-receptor inhibiting 3-(4-phenoxymethylpiperidino)-propyl-phenyl ethers |
| NL7712220A NL7712220A (nl) | 1976-11-12 | 1977-11-07 | Nieuwe aminopropanolderivaten, werkwijze voor de bereiding van dergelijke derivaten en ge- neesmiddelen met deze derivaten als werkzame verbinding. |
| AR269873A AR218643A1 (es) | 1976-11-12 | 1977-11-07 | Procedimiento para preparar 3-(4-fenoxi-metil-piperidino)-propoxi derivados de indol,indazol,bezimidazol y benzotriazol y sus sales |
| YU02664/77A YU266477A (en) | 1976-11-12 | 1977-11-07 | Process for preparing amino propanols and salts thereof |
| IL53323A IL53323A (en) | 1976-11-12 | 1977-11-07 | 1-(4-phenoxymethylpiperidino)-2-hydroxy-3-(indolyl(indazolyl,benzimidazolyl or benzotriazolyl)oxy)propanes,their preparation and pharmaceutical compositions containing them |
| AU30466/77A AU510284B2 (en) | 1976-11-12 | 1977-11-08 | 3(-(4-phenoxymethyl piperidino)-propoxy) indole or indazole or benzimidazole or benzotriazole |
| CS777291A CS228106B2 (en) | 1976-11-12 | 1977-11-08 | Production of novel derivatives of 3-/4-phenoxymethylpiperidino/-propanol |
| DD7700201951A DD133801A5 (de) | 1976-11-12 | 1977-11-08 | Neue aminopropanolderivate,verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| FI773346A FI62077C (fi) | 1976-11-12 | 1977-11-08 | Foerfarande foer framstaellning av farmaceutiskt anvaendbara fenoximetylpiperidinopropanolderivat |
| IT29456/77A IT1087490B (it) | 1976-11-12 | 1977-11-08 | Derivati aminopropanolici,processo per la loro preparazione e farmaci che li contengono |
| GB46415/77A GB1541547A (en) | 1976-11-12 | 1977-11-08 | 4-phenoxymethylpiperidine derivatives |
| PL21334777A PL111948B1 (en) | 1977-08-20 | 1977-11-09 | Method of manufacture of novel derivatives of aminopropanol |
| PL1977213346A PL112683B1 (en) | 1976-11-12 | 1977-11-09 | Process for preparing novel derivatives of aminopropanol |
| CA290,495A CA1086740A (en) | 1976-11-12 | 1977-11-09 | Piperidinopropyl derivatives and the preparation thereof |
| CH1367177A CH636099A5 (de) | 1976-11-12 | 1977-11-09 | Verfahren zur herstellung von piperidinopropanolderivaten. |
| PL21334877A PL112154B1 (en) | 1977-08-20 | 1977-11-09 | Method of preparation of novel aminopropanol derivatives |
| PL1977201997A PL110782B1 (en) | 1976-11-12 | 1977-11-09 | Method of producing new derivatives of aminopropanol |
| FR7733907A FR2370744A1 (fr) | 1976-11-12 | 1977-11-10 | Nouveaux derives d'aminopropanol, procede pour leur preparation et medicaments contenant ces composes |
| HU77BO1689A HU177410B (en) | 1976-11-12 | 1977-11-10 | Process for preparing new piperidino-propanol derivatives |
| SE7712720A SE7712720L (sv) | 1976-11-12 | 1977-11-10 | Piperidinopropylderivat |
| LU7778498A LU78498A1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1976-11-12 | 1977-11-11 | |
| JP13559177A JPS5363385A (en) | 1976-11-12 | 1977-11-11 | Novel aminopropanole derivative process for preparing same and medicine having vasodilating and betaaacceptor interupiing efect |
| DK500677A DK500677A (da) | 1976-11-12 | 1977-11-11 | Aminopropanolderivater fremgangsmaade til fremstilling heraf og laegemidler indeholdende disse forbindelser |
| AT808277A AT361476B (de) | 1976-11-12 | 1977-11-11 | Verfahren zur herstellung von neuen amino- propanolderivaten und deren salzen |
| CS785459A CS228108B2 (cs) | 1977-08-20 | 1978-08-21 | Způsob výroby nových derivátů 3-(4-fenoxymethylpiperidino)propanolu |
| CS785460A CS228109B2 (cs) | 1977-08-20 | 1978-08-21 | Způsob výroby nových derivátů 3-(4-fenoxymethylpiperidino)propanolu |
| CS785461A CS228110B2 (en) | 1976-11-12 | 1978-08-21 | Production of novel derivatives of 3-/4-phenoxymethylpi |
| ES472746A ES472746A1 (es) | 1976-11-12 | 1978-08-22 | Procedimiento para la preparacion de derivados de aminopro- panol |
| ES472747A ES472747A1 (es) | 1976-11-12 | 1978-08-22 | Procedimiento para la preparacion de derivados de aminopro- panol |
| SU782674802A SU826955A3 (ru) | 1976-11-12 | 1978-10-20 | Способ получения производных аминопропанола или их солей 1 |
| SU782675553A SU890975A3 (ru) | 1976-11-12 | 1978-10-20 | Способ получени производных аминопропанола или их солей |
| AR275657A AR221081A1 (es) | 1976-11-12 | 1979-02-28 | Procedimiento para preparar derivados de fenoximetil-piperidino-propoxi-indol |
| AR275655A AR221868A1 (es) | 1976-11-12 | 1979-02-28 | Un procedimiento para preparar 3-(4-fenoxi-metil-piperidino)-propoxi derivados de indol,indazol,benzimidazol y benzotriazol y sus sales |
| AT649879A AT361479B (de) | 1976-11-12 | 1979-10-04 | Verfahren zur herstellung von neuen aminopro- panolderivaten und deren salzen |
| AT650079A AT362374B (de) | 1977-08-20 | 1979-10-04 | Verfahren zur herstellung von neuen amino- propanolderivaten und deren salzen |
| AT649979A AT362373B (de) | 1977-08-20 | 1979-10-04 | Verfahren zur herstellung von neuen amino- propanolderivaten und deren salzen |
| CH367682A CH639086A5 (de) | 1976-11-12 | 1982-06-14 | Verfahren zur herstellung von piperidinopropanolderivaten. |
| CH233783A CH643554A5 (de) | 1976-11-12 | 1983-05-02 | Verfahren zur herstellung von piperidinopropanolderivaten. |
| YU01289/83A YU128983A (en) | 1976-11-12 | 1983-06-09 | Process for preparing 4-(2-hydroxy-3-(4-phenoxy-methyl-pyperidino)-propoxy)indol and salts and esters thereof |
| YU01288/83A YU128883A (en) | 1976-11-12 | 1983-06-09 | Process for preparing 4-(2-hydroxy-3-(4-phenoxy-methyl-pyperidino)-propoxy)indol and salts and esters thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19772737630 DE2737630A1 (de) | 1977-08-20 | 1977-08-20 | Neue aminopropanolderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE2737630A1 DE2737630A1 (de) | 1979-03-01 |
| DE2737630C2 true DE2737630C2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1987-11-05 |
Family
ID=6016909
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19772737630 Granted DE2737630A1 (de) | 1976-11-12 | 1977-08-20 | Neue aminopropanolderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
Country Status (2)
| Country | Link |
|---|---|
| DE (1) | DE2737630A1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) |
| PL (2) | PL111948B1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8575364B2 (en) | 2008-10-30 | 2013-11-05 | Janssen Pharmaceutica Nv | Modulators of serotonin receptor |
| US8642583B2 (en) | 2008-10-30 | 2014-02-04 | Janssen Pharmaceutica Nv | Serotonin receptor modulators |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0005828B1 (de) * | 1978-06-06 | 1981-03-11 | Hoechst Aktiengesellschaft | Neue substituierte Phenylpiperazinderivate, diese enthaltende Arzneimittel und Verfahren zu deren Herstellung |
| DE2834114A1 (de) * | 1978-08-01 | 1980-02-14 | Schering Ag | Polyalkoxyphenylpyrrolidone iii, verfahren zu ihrer herstellung und ihre verwendung |
| DE2905876A1 (de) * | 1979-02-16 | 1980-08-28 | Boehringer Mannheim Gmbh | Neue piperidinopropylderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| SE8003278L (sv) | 1979-05-04 | 1980-11-05 | Continental Pharma | Fenyletylaminderivat |
| DE2939292A1 (de) * | 1979-09-28 | 1981-04-09 | Boehringer Mannheim Gmbh, 6800 Mannheim | N-phenoxyalkylpiperidin-derivate, verfahrenn zu deren herstellung sowie diese verbindungen enthaltende arzneimittel |
| SE8604566D0 (sv) * | 1986-10-27 | 1986-10-27 | Haessle Ab | Novel compunds |
| DE3721260A1 (de) * | 1987-06-27 | 1989-01-12 | Beiersdorf Ag | Neue indolylpropanole, verfahren zu ihrer herstellung und ihre verwendung sowie die verbindungen enthaltende zubereitungen |
| FR2667317B1 (fr) * | 1990-10-02 | 1992-12-04 | Synthelabo | Derives de 2-aminopyrimidine-4-carboxamide, leur preparation et leur application en therapeutique. |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2651574A1 (de) * | 1976-11-12 | 1978-05-18 | Boehringer Mannheim Gmbh | Ein neues aminopropanol-derivat und verfahren zu dessen herstellung |
-
1977
- 1977-08-20 DE DE19772737630 patent/DE2737630A1/de active Granted
- 1977-11-09 PL PL21334777A patent/PL111948B1/pl unknown
- 1977-11-09 PL PL21334877A patent/PL112154B1/pl unknown
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8575364B2 (en) | 2008-10-30 | 2013-11-05 | Janssen Pharmaceutica Nv | Modulators of serotonin receptor |
| US8642583B2 (en) | 2008-10-30 | 2014-02-04 | Janssen Pharmaceutica Nv | Serotonin receptor modulators |
| US8957059B2 (en) | 2008-10-30 | 2015-02-17 | Janssen Pharmaceutica Nv | Modulators of serotonin receptors |
| US9981909B2 (en) | 2008-10-30 | 2018-05-29 | Janssen Pharmaceutica Nv | Serotonin receptor modulators |
Also Published As
| Publication number | Publication date |
|---|---|
| DE2737630A1 (de) | 1979-03-01 |
| PL111948B1 (en) | 1980-09-30 |
| PL112154B1 (en) | 1980-09-30 |
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| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |