FI62052C - Foerfarande foer framstaellning av farmakologiskt vaerdefulla 4-aminofenyletanolaminer med saerskilt beta2-mimetisk och ala1-blockerande verkan - Google Patents
Foerfarande foer framstaellning av farmakologiskt vaerdefulla 4-aminofenyletanolaminer med saerskilt beta2-mimetisk och ala1-blockerande verkan Download PDFInfo
- Publication number
- FI62052C FI62052C FI3770/73A FI377073A FI62052C FI 62052 C FI62052 C FI 62052C FI 3770/73 A FI3770/73 A FI 3770/73A FI 377073 A FI377073 A FI 377073A FI 62052 C FI62052 C FI 62052C
- Authority
- FI
- Finland
- Prior art keywords
- amino
- phenyl
- ethanol
- melting point
- tert
- Prior art date
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- 230000000144 pharmacologic effect Effects 0.000 title description 2
- -1 cyano, carboxy Chemical group 0.000 claims description 150
- 238000000034 method Methods 0.000 claims description 111
- 150000001875 compounds Chemical class 0.000 claims description 102
- 239000000203 mixture Substances 0.000 claims description 29
- 229910052739 hydrogen Inorganic materials 0.000 claims description 25
- 239000001257 hydrogen Substances 0.000 claims description 23
- 238000002360 preparation method Methods 0.000 claims description 20
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 19
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 18
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 15
- 239000000460 chlorine Substances 0.000 claims description 15
- 229910052794 bromium Inorganic materials 0.000 claims description 14
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 13
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
- 230000000694 effects Effects 0.000 claims description 11
- 125000002252 acyl group Chemical group 0.000 claims description 10
- 125000006239 protecting group Chemical group 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 9
- 125000003342 alkenyl group Chemical group 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 9
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 8
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 claims description 8
- 229910052740 iodine Inorganic materials 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 230000007062 hydrolysis Effects 0.000 claims description 6
- 238000006460 hydrolysis reaction Methods 0.000 claims description 6
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 6
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 5
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 125000003277 amino group Chemical group 0.000 claims description 4
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 150000007522 mineralic acids Chemical class 0.000 claims description 4
- 150000007524 organic acids Chemical class 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 235000005985 organic acids Nutrition 0.000 claims description 3
- OPQUFBKKROUGSH-UHFFFAOYSA-N 2-amino-1-(4-aminophenyl)ethanol Chemical class NCC(O)C1=CC=C(N)C=C1 OPQUFBKKROUGSH-UHFFFAOYSA-N 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000006193 alkinyl group Chemical group 0.000 claims 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- 230000029087 digestion Effects 0.000 claims 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 1
- 125000002346 iodo group Chemical group I* 0.000 claims 1
- 238000002844 melting Methods 0.000 description 412
- 230000008018 melting Effects 0.000 description 410
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 241
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 192
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 184
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 131
- 239000012279 sodium borohydride Substances 0.000 description 121
- 229910000033 sodium borohydride Inorganic materials 0.000 description 121
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 104
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 99
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 63
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 58
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 57
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 54
- 239000000243 solution Substances 0.000 description 49
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 36
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 31
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 28
- 229910021529 ammonia Inorganic materials 0.000 description 27
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
- 239000002904 solvent Substances 0.000 description 23
- 239000003054 catalyst Substances 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 21
- 239000000741 silica gel Substances 0.000 description 19
- 229910002027 silica gel Inorganic materials 0.000 description 19
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 18
- 229910052938 sodium sulfate Inorganic materials 0.000 description 17
- 235000011152 sodium sulphate Nutrition 0.000 description 17
- 238000003756 stirring Methods 0.000 description 15
- 150000002431 hydrogen Chemical class 0.000 description 14
- 238000003776 cleavage reaction Methods 0.000 description 13
- 230000007017 scission Effects 0.000 description 13
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
- 229960000583 acetic acid Drugs 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- 238000001704 evaporation Methods 0.000 description 12
- 230000008020 evaporation Effects 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 12
- 238000001816 cooling Methods 0.000 description 11
- 239000003480 eluent Substances 0.000 description 11
- 239000012071 phase Substances 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 10
- 239000013078 crystal Substances 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- 239000007858 starting material Substances 0.000 description 10
- MHWMCEILWDYPJN-UHFFFAOYSA-N 1-[4-amino-3-chloro-5-(trifluoromethyl)phenyl]-2-(cyclobutylamino)ethanol;hydrochloride Chemical compound Cl.C1=C(C(F)(F)F)C(N)=C(Cl)C=C1C(O)CNC1CCC1 MHWMCEILWDYPJN-UHFFFAOYSA-N 0.000 description 9
- CGCHJJMCSJZEGH-UHFFFAOYSA-N 2-amino-5-[2-(tert-butylamino)-1-hydroxyethyl]-3-chlorobenzonitrile Chemical compound CC(C)(C)NCC(O)C1=CC(Cl)=C(N)C(C#N)=C1 CGCHJJMCSJZEGH-UHFFFAOYSA-N 0.000 description 9
- 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 9
- LWJSGOMCMMDPEN-UHFFFAOYSA-N Mapenterol hydrochloride Chemical compound Cl.CCC(C)(C)NCC(O)C1=CC(Cl)=C(N)C(C(F)(F)F)=C1 LWJSGOMCMMDPEN-UHFFFAOYSA-N 0.000 description 9
- 125000003118 aryl group Chemical group 0.000 description 9
- 238000004587 chromatography analysis Methods 0.000 description 9
- 239000012280 lithium aluminium hydride Substances 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- 229910052708 sodium Inorganic materials 0.000 description 9
- GIZXRBFANOUKFV-UHFFFAOYSA-N 1-[4-amino-3-bromo-5-(trifluoromethyl)phenyl]-2-(propan-2-ylamino)ethanol;hydrochloride Chemical compound Cl.CC(C)NCC(O)C1=CC(Br)=C(N)C(C(F)(F)F)=C1 GIZXRBFANOUKFV-UHFFFAOYSA-N 0.000 description 8
- MMCDXJOMPMIKGP-UHFFFAOYSA-N Mabuterol hydrochloride Chemical compound [Cl-].CC(C)(C)[NH2+]CC(O)C1=CC(Cl)=C(N)C(C(F)(F)F)=C1 MMCDXJOMPMIKGP-UHFFFAOYSA-N 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- 239000008346 aqueous phase Substances 0.000 description 8
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 8
- 238000005984 hydrogenation reaction Methods 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- WNHISWIZEMKFRF-UHFFFAOYSA-N 1-(4-amino-3-bromo-5-nitrophenyl)-2-(tert-butylamino)ethanol Chemical compound CC(C)(C)NCC(O)C1=CC(Br)=C(N)C([N+]([O-])=O)=C1 WNHISWIZEMKFRF-UHFFFAOYSA-N 0.000 description 7
- QQBVYZBOKKTSBP-UHFFFAOYSA-N 1-(4-amino-3-chloro-5-fluorophenyl)-2-(cyclopropylamino)ethanol;hydrochloride Chemical compound Cl.C1=C(Cl)C(N)=C(F)C=C1C(O)CNC1CC1 QQBVYZBOKKTSBP-UHFFFAOYSA-N 0.000 description 7
- CZJFFCHZGPFPRG-UHFFFAOYSA-N 1-(4-amino-3-chloro-5-fluorophenyl)-2-(tert-butylamino)ethanol;hydrochloride Chemical compound [Cl-].CC(C)(C)[NH2+]CC(O)C1=CC(F)=C(N)C(Cl)=C1 CZJFFCHZGPFPRG-UHFFFAOYSA-N 0.000 description 7
- SBIZLZBFKBWZKL-UHFFFAOYSA-N 1-(4-amino-3-chloro-5-nitrophenyl)-2-(tert-butylamino)ethanol Chemical compound CC(C)(C)NCC(O)C1=CC(Cl)=C(N)C([N+]([O-])=O)=C1 SBIZLZBFKBWZKL-UHFFFAOYSA-N 0.000 description 7
- ZTOJVVBTYKAIKQ-UHFFFAOYSA-N 1-(4-amino-3-fluorophenyl)-2-(tert-butylamino)ethanol;hydrochloride Chemical group [Cl-].CC(C)(C)[NH2+]CC(O)C1=CC=C(N)C(F)=C1 ZTOJVVBTYKAIKQ-UHFFFAOYSA-N 0.000 description 7
- ADMVUCDLKDANSY-UHFFFAOYSA-N 1-[4-amino-3-chloro-5-(trifluoromethyl)phenyl]-2-(propan-2-ylamino)ethanol Chemical compound CC(C)NCC(O)C1=CC(Cl)=C(N)C(C(F)(F)F)=C1 ADMVUCDLKDANSY-UHFFFAOYSA-N 0.000 description 7
- YYVOMLJFTZMOJM-UHFFFAOYSA-N 2-amino-5-[2-[tert-butyl(hydroxy)amino]-1-hydroxyethyl]-3-chlorobenzonitrile;hydrochloride Chemical compound Cl.CC(C)(C)N(O)CC(O)C1=CC(Cl)=C(N)C(C#N)=C1 YYVOMLJFTZMOJM-UHFFFAOYSA-N 0.000 description 7
- 238000009835 boiling Methods 0.000 description 7
- 238000002425 crystallisation Methods 0.000 description 7
- 230000008025 crystallization Effects 0.000 description 7
- 239000012362 glacial acetic acid Substances 0.000 description 7
- 229910052987 metal hydride Inorganic materials 0.000 description 7
- 150000004681 metal hydrides Chemical class 0.000 description 7
- KMQUMSBPELGREK-UHFFFAOYSA-N 1-(4-amino-3-bromo-5-fluorophenyl)-2-(propan-2-ylamino)ethanol;hydrochloride Chemical compound Cl.CC(C)NCC(O)C1=CC(F)=C(N)C(Br)=C1 KMQUMSBPELGREK-UHFFFAOYSA-N 0.000 description 6
- CNRVBHZYPJXYDD-UHFFFAOYSA-N 2-amino-3-bromo-5-[2-(tert-butylamino)-1-hydroxyethyl]benzonitrile;hydrochloride Chemical group [Cl-].CC(C)(C)[NH2+]CC(O)C1=CC(Br)=C(N)C(C#N)=C1 CNRVBHZYPJXYDD-UHFFFAOYSA-N 0.000 description 6
- GCOOAOCXKMHBOF-UHFFFAOYSA-N 2-amino-3-chloro-5-[2-(cyclopentylamino)-1-hydroxyethyl]benzonitrile;hydrochloride Chemical compound Cl.C1=C(C#N)C(N)=C(Cl)C=C1C(O)CNC1CCCC1 GCOOAOCXKMHBOF-UHFFFAOYSA-N 0.000 description 6
- TVNWRWIXFJERNS-UHFFFAOYSA-N 2-amino-3-fluoro-5-[1-hydroxy-2-(propan-2-ylamino)ethyl]benzonitrile;hydrochloride Chemical group Cl.CC(C)NCC(O)C1=CC(F)=C(N)C(C#N)=C1 TVNWRWIXFJERNS-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 125000000304 alkynyl group Chemical group 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 238000001640 fractional crystallisation Methods 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- NGCIPBQOTTZMOD-UHFFFAOYSA-N 1-(4-amino-3-bromo-5-fluorophenyl)-2-(cyclobutylamino)ethanol;hydrochloride Chemical compound Cl.C1=C(Br)C(N)=C(F)C=C1C(O)CNC1CCC1 NGCIPBQOTTZMOD-UHFFFAOYSA-N 0.000 description 5
- LSLBOXLMMCSNAL-UHFFFAOYSA-N 1-(4-amino-3-bromo-5-fluorophenyl)-2-(tert-butylamino)ethanol Chemical compound CC(C)(C)NCC(O)C1=CC(F)=C(N)C(Br)=C1 LSLBOXLMMCSNAL-UHFFFAOYSA-N 0.000 description 5
- GGBSTCRJHKFMKF-UHFFFAOYSA-N 1-[4-amino-3-(trifluoromethyl)phenyl]-2-(tert-butylamino)ethanol;hydrochloride Chemical compound Cl.CC(C)(C)NCC(O)C1=CC=C(N)C(C(F)(F)F)=C1 GGBSTCRJHKFMKF-UHFFFAOYSA-N 0.000 description 5
- LCLPMNYAKMFCLE-UHFFFAOYSA-N 2-amino-3-bromo-5-[1-hydroxy-2-(propan-2-ylamino)ethyl]benzonitrile;hydrochloride Chemical compound Cl.CC(C)NCC(O)C1=CC(Br)=C(N)C(C#N)=C1 LCLPMNYAKMFCLE-UHFFFAOYSA-N 0.000 description 5
- PDTDQNZOKGDEJX-UHFFFAOYSA-N 2-amino-3-chloro-5-[1-hydroxy-2-(2-methylbutan-2-ylamino)ethyl]benzonitrile;hydrochloride Chemical compound Cl.CCC(C)(C)NCC(O)C1=CC(Cl)=C(N)C(C#N)=C1 PDTDQNZOKGDEJX-UHFFFAOYSA-N 0.000 description 5
- NESCJTFKQSIWRR-UHFFFAOYSA-N 2-amino-5-[1-hydroxy-2-(2-methylbutan-2-ylamino)ethyl]benzonitrile Chemical compound CCC(C)(C)NCC(O)C1=CC=C(N)C(C#N)=C1 NESCJTFKQSIWRR-UHFFFAOYSA-N 0.000 description 5
- ZVTZRUOSPROATJ-UHFFFAOYSA-N 2-amino-5-[2-(butan-2-ylamino)-1-hydroxyethyl]-3-chlorobenzonitrile;dihydrochloride Chemical compound Cl.Cl.CCC(C)NCC(O)C1=CC(Cl)=C(N)C(C#N)=C1 ZVTZRUOSPROATJ-UHFFFAOYSA-N 0.000 description 5
- MKYVGPFLFZQOAM-UHFFFAOYSA-N 2-amino-5-[2-(cyclobutylamino)-1-hydroxyethyl]benzonitrile;hydrobromide Chemical compound Br.C1=C(C#N)C(N)=CC=C1C(O)CNC1CCC1 MKYVGPFLFZQOAM-UHFFFAOYSA-N 0.000 description 5
- NJKULRKQHJWHCU-UHFFFAOYSA-N 2-amino-5-[2-[1-(1,3-benzodioxol-5-yl)propan-2-ylamino]-1-hydroxyethyl]-3-chlorobenzonitrile hydrochloride Chemical compound Cl.NC1=C(C=C(C=C1C#N)C(CNC(CC1=CC2=C(C=C1)OCO2)C)O)Cl NJKULRKQHJWHCU-UHFFFAOYSA-N 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 229910052736 halogen Inorganic materials 0.000 description 5
- 150000002367 halogens Chemical class 0.000 description 5
- SNHMUERNLJLMHN-UHFFFAOYSA-N iodobenzene Chemical compound IC1=CC=CC=C1 SNHMUERNLJLMHN-UHFFFAOYSA-N 0.000 description 5
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 5
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- GMSPBYXILXZESB-UHFFFAOYSA-N 1-(4-amino-3-fluoro-5-iodophenyl)-2-(cyclopropylamino)ethanol;hydrochloride Chemical compound Cl.C1=C(I)C(N)=C(F)C=C1C(O)CNC1CC1 GMSPBYXILXZESB-UHFFFAOYSA-N 0.000 description 4
- IPBUQGQOWCKZHO-UHFFFAOYSA-N 1-(4-amino-3-fluorophenyl)-2-(tert-butylamino)ethanol Chemical compound CC(C)(C)NCC(O)C1=CC=C(N)C(F)=C1 IPBUQGQOWCKZHO-UHFFFAOYSA-N 0.000 description 4
- 229940013085 2-diethylaminoethanol Drugs 0.000 description 4
- BDOMTLWWSOBLSC-UHFFFAOYSA-N CC(C)(C)N1[CH-]OC(C1=O)C2=CC(=C(C(=C2)Br)N)F Chemical compound CC(C)(C)N1[CH-]OC(C1=O)C2=CC(=C(C(=C2)Br)N)F BDOMTLWWSOBLSC-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 4
- 239000007868 Raney catalyst Substances 0.000 description 4
- 229910000564 Raney nickel Inorganic materials 0.000 description 4
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
- 229910004298 SiO 2 Inorganic materials 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- JSJCTEKTBOKRST-UHFFFAOYSA-N mabuterol Chemical compound CC(C)(C)NCC(O)C1=CC(Cl)=C(N)C(C(F)(F)F)=C1 JSJCTEKTBOKRST-UHFFFAOYSA-N 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- 229910017604 nitric acid Inorganic materials 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
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- YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000000266 alpha-aminoacyl group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- MOOAHMCRPCTRLV-UHFFFAOYSA-N boron sodium Chemical compound [B].[Na] MOOAHMCRPCTRLV-UHFFFAOYSA-N 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- OPXKTCUYRHXSBK-UHFFFAOYSA-N clenbuterol hydrochloride Chemical compound Cl.CC(C)(C)NCC(O)C1=CC(Cl)=C(N)C(Cl)=C1 OPXKTCUYRHXSBK-UHFFFAOYSA-N 0.000 description 1
- 239000012045 crude solution Substances 0.000 description 1
- KZZKOVLJUKWSKX-UHFFFAOYSA-N cyclobutanamine Chemical compound NC1CCC1 KZZKOVLJUKWSKX-UHFFFAOYSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- GUBNMFJOJGDCEL-UHFFFAOYSA-N dicyclomine hydrochloride Chemical group [Cl-].C1CCCCC1C1(C(=O)OCC[NH+](CC)CC)CCCCC1 GUBNMFJOJGDCEL-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000210 effect on cough Effects 0.000 description 1
- DZGCGKFAPXFTNM-UHFFFAOYSA-N ethanol;hydron;chloride Chemical compound Cl.CCO DZGCGKFAPXFTNM-UHFFFAOYSA-N 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000013213 extrapolation Methods 0.000 description 1
- 125000001207 fluorophenyl group Chemical group 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 239000000413 hydrolysate Substances 0.000 description 1
- AUONNNVJUCSETH-UHFFFAOYSA-N icosanoyl icosanoate Chemical compound CCCCCCCCCCCCCCCCCCCC(=O)OC(=O)CCCCCCCCCCCCCCCCCCC AUONNNVJUCSETH-UHFFFAOYSA-N 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N mandelic acid Chemical compound OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 229940101209 mercuric oxide Drugs 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- ZGTVOKMLPTXLBD-UHFFFAOYSA-N n-[2-chloro-6-fluoro-4-[1-hydroxy-2-(propan-2-ylamino)ethyl]phenyl]acetamide;hydrochloride Chemical compound Cl.CC(C)NCC(O)C1=CC(F)=C(NC(C)=O)C(Cl)=C1 ZGTVOKMLPTXLBD-UHFFFAOYSA-N 0.000 description 1
- BWUOVJAZFFNYJK-UHFFFAOYSA-N n-[4-[2-(cyclopropylamino)-1-hydroxyethyl]-2-fluorophenyl]acetamide Chemical compound C1=C(F)C(NC(=O)C)=CC=C1C(O)CNC1CC1 BWUOVJAZFFNYJK-UHFFFAOYSA-N 0.000 description 1
- RZEWIKVAGDKVHB-UHFFFAOYSA-N n-[4-[2-(tert-butylamino)-1-hydroxyethyl]-2-(trifluoromethyl)phenyl]acetamide;hydrochloride Chemical compound Cl.CC(=O)NC1=CC=C(C(O)CNC(C)(C)C)C=C1C(F)(F)F RZEWIKVAGDKVHB-UHFFFAOYSA-N 0.000 description 1
- DNWLWUFEZLIXHS-UHFFFAOYSA-N n-[4-[2-(tert-butylamino)-1-hydroxyethyl]-2-chloro-6-fluorophenyl]propanamide Chemical compound CCC(=O)NC1=C(F)C=C(C(O)CNC(C)(C)C)C=C1Cl DNWLWUFEZLIXHS-UHFFFAOYSA-N 0.000 description 1
- KQYOITMXYOUDQD-UHFFFAOYSA-N n-[4-[2-(tert-butylamino)-1-hydroxyethyl]-2-chloro-6-nitrophenyl]acetamide;hydrochloride Chemical compound Cl.CC(=O)NC1=C(Cl)C=C(C(O)CNC(C)(C)C)C=C1[N+]([O-])=O KQYOITMXYOUDQD-UHFFFAOYSA-N 0.000 description 1
- DEGUPJPRBJYELI-UHFFFAOYSA-N n-[4-[2-(tert-butylamino)-1-hydroxyethyl]-2-fluorophenyl]benzamide Chemical compound FC1=CC(C(O)CNC(C)(C)C)=CC=C1NC(=O)C1=CC=CC=C1 DEGUPJPRBJYELI-UHFFFAOYSA-N 0.000 description 1
- TYRGLVWXHJRKMT-QMMMGPOBSA-N n-benzyloxycarbonyl-l-serine-betalactone Chemical compound OC(=O)[C@H](C)NC(=O)OCC1=CC=CC=C1 TYRGLVWXHJRKMT-QMMMGPOBSA-N 0.000 description 1
- AHAXISXGFCFQGE-UHFFFAOYSA-N n-oxoformamide Chemical compound O=CN=O AHAXISXGFCFQGE-UHFFFAOYSA-N 0.000 description 1
- 230000003533 narcotic effect Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 230000000802 nitrating effect Effects 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- HVZWVEKIQMJYIK-UHFFFAOYSA-N nitryl chloride Chemical compound [O-][N+](Cl)=O HVZWVEKIQMJYIK-UHFFFAOYSA-N 0.000 description 1
- 150000007530 organic bases Chemical group 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000003884 phenylalkyl group Chemical group 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- OTNVGWMVOULBFZ-UHFFFAOYSA-N sodium;hydrochloride Chemical compound [Na].Cl OTNVGWMVOULBFZ-UHFFFAOYSA-N 0.000 description 1
- 239000001119 stannous chloride Substances 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000010414 supernatant solution Substances 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
- C07C215/02—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C215/22—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated
- C07C215/28—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings
- C07C215/30—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings containing hydroxy groups and carbon atoms of six-membered aromatic rings bound to the same carbon atom of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/04—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/58—Radicals substituted by nitrogen atoms
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pain & Pain Management (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FI812795A FI69837C (fi) | 1972-12-18 | 1981-09-08 | Foerfarande foer framstaellning av farmakologiskt vaerdeful 4-mino-fenyloxazolidin och dess syraadditionssalter |
Applications Claiming Priority (8)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE2261914A DE2261914C3 (de) | 1972-12-18 | 1972-12-18 | Amino-phenyl-äthanolamine und deren Säureadditionssalze, Verfahren zu deren Herstellung und Arzneimittel |
DE2261914 | 1972-12-18 | ||
DE2345442 | 1973-09-08 | ||
DE19732345442 DE2345442C2 (de) | 1973-09-08 | 1973-09-08 | d- und l-Phenyläthanolamine und deren Salze, Herstellungsverfahren und Arzneimittel auf deren Basis |
DE2351281 | 1973-10-12 | ||
DE19732351281 DE2351281C3 (de) | 1973-10-12 | 1973-10-12 | Aminophenyl-äthanolamin-Derivate, deren Herstellung und Verwendung |
DE2354961 | 1973-11-02 | ||
DE2354961A DE2354961C2 (de) | 1973-11-02 | 1973-11-02 | Verfahren zur Herstellung von Aminophenyl-äthanolaminen |
Publications (2)
Publication Number | Publication Date |
---|---|
FI62052B FI62052B (fi) | 1982-07-30 |
FI62052C true FI62052C (fi) | 1982-11-10 |
Family
ID=27431596
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
FI3770/73A FI62052C (fi) | 1972-12-18 | 1973-12-10 | Foerfarande foer framstaellning av farmakologiskt vaerdefulla 4-aminofenyletanolaminer med saerskilt beta2-mimetisk och ala1-blockerande verkan |
Country Status (20)
Families Citing this family (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2430486A1 (fr) * | 1978-07-07 | 1980-02-01 | Oreal | Conditionnement d'un produit desinfectant et desodorisant pour cuvette de toilettes |
NL8105170A (nl) * | 1980-12-10 | 1982-07-01 | Thomae Gmbh Dr K | Nieuwe fenylalkylaminen, werkwijze ter bereiding daarvan en de toepassing daarvan als geneesmiddelen. |
FR2515177A1 (fr) * | 1981-10-28 | 1983-04-29 | Lafon Labor | Nouveaux derives de 1-(aminophenyl)-2-amino-1-ethanol, leur procede de preparation et leur utilisation en therapeutique |
GB8426191D0 (en) * | 1984-10-17 | 1984-11-21 | Glaxo Holdings Ltd | Chemical compounds |
US4943591A (en) * | 1984-10-17 | 1990-07-24 | Glaxo Group Limited | Dichloroaniline derivatives |
US4863959A (en) * | 1985-10-17 | 1989-09-05 | American Cyanamid Company | Anthranilonitrile derivatives as useful agents for promoting growth, improving feed efficiency, and for increasing the lean meat to fat ratio of warm-blooded animals |
ES2021267B3 (es) * | 1985-10-17 | 1991-11-01 | American Cyanamid Co | Metodo para promover el crecimiento, mejorar la eficacia alimenticia y para acelerar el engorde en animales de sangre caliente. |
GB8603475D0 (en) * | 1986-02-12 | 1986-03-19 | Glaxo Group Ltd | Chemical compounds |
GB8703007D0 (en) * | 1987-02-10 | 1987-03-18 | Glaxo Group Ltd | Chemical compounds |
EP0278727A3 (en) * | 1987-02-10 | 1990-03-14 | Glaxo Group Limited | 1-(4-amino-3-chloro-5-trifluoromethylphenyl)-2-(substituted amino)ethanol derivatives and their use in the treatment of respiratory disease |
CA2537124C (en) * | 2003-08-29 | 2012-08-07 | Mitsui Chemicals, Inc. | Agricultural/horticultural insecticide and method for using the same |
GB0604822D0 (en) * | 2006-03-09 | 2006-04-19 | Arakis Ltd | The treatment of inflammatory disorders and pain |
CN100497296C (zh) * | 2006-07-07 | 2009-06-10 | 沈阳药科大学 | 旋光活性的苯乙醇胺类化合物及其制法 |
GB201714745D0 (en) | 2017-09-13 | 2017-10-25 | Atrogi Ab | New compounds and uses |
GB201714736D0 (en) | 2017-09-13 | 2017-10-25 | Atrogi Ab | New compounds and uses |
GB201714734D0 (en) | 2017-09-13 | 2017-10-25 | Atrogi Ab | New compounds and uses |
GB201903832D0 (en) | 2019-03-20 | 2019-05-01 | Atrogi Ab | New compounds and methods |
-
1973
- 1973-11-26 NL NLAANVRAGE7316139,A patent/NL176168C/xx not_active IP Right Cessation
- 1973-12-04 BG BG026781A patent/BG21209A3/xx unknown
- 1973-12-10 FI FI3770/73A patent/FI62052C/fi active
- 1973-12-14 CH CH1755873A patent/CH605622A5/xx not_active IP Right Cessation
- 1973-12-14 CH CH1178977A patent/CH614188A5/xx not_active IP Right Cessation
- 1973-12-14 RO RO7300077002A patent/RO63025A/ro unknown
- 1973-12-14 DD DD175409A patent/DD111574A5/xx unknown
- 1973-12-17 IL IL43837A patent/IL43837A/en unknown
- 1973-12-17 SE SE7317035A patent/SE409700B/sv unknown
- 1973-12-17 CA CA188,272A patent/CA1027955A/en not_active Expired
- 1973-12-17 GB GB5834473A patent/GB1445740A/en not_active Expired
- 1973-12-17 DK DK684873A patent/DK150502C/da not_active IP Right Cessation
- 1973-12-17 PL PL73182408A patent/PL97194B1/pl unknown
- 1973-12-17 NO NO4814/73A patent/NO137782C/no unknown
- 1973-12-17 JP JP48141734A patent/JPS5811852B2/ja not_active Expired
- 1973-12-17 HU HUTO949A patent/HU168701B/hu unknown
- 1973-12-18 IE IE2292/73A patent/IE39065B1/xx unknown
- 1973-12-18 FR FR7345290A patent/FR2210414B1/fr not_active Expired
-
1975
- 1975-05-19 KR KR7501095A patent/KR850001916B1/ko not_active Expired
-
1980
- 1980-02-28 HK HK66/80A patent/HK6680A/xx unknown
-
1988
- 1988-12-30 MY MY58344/73A patent/MY8800145A/xx unknown
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