DE4135474A1 - 2-aminomethyl-chromane - Google Patents
2-aminomethyl-chromaneInfo
- Publication number
- DE4135474A1 DE4135474A1 DE4135474A DE4135474A DE4135474A1 DE 4135474 A1 DE4135474 A1 DE 4135474A1 DE 4135474 A DE4135474 A DE 4135474A DE 4135474 A DE4135474 A DE 4135474A DE 4135474 A1 DE4135474 A1 DE 4135474A1
- Authority
- DE
- Germany
- Prior art keywords
- carbon atoms
- chain
- straight
- branched alkyl
- optionally
- 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.)
- Withdrawn
Links
- 238000011282 treatment Methods 0.000 claims abstract description 13
- 150000001412 amines Chemical class 0.000 claims abstract description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 11
- 239000003814 drug Substances 0.000 claims abstract description 9
- 150000001299 aldehydes Chemical class 0.000 claims abstract description 8
- 210000003169 central nervous system Anatomy 0.000 claims abstract description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 72
- 150000001875 compounds Chemical class 0.000 claims description 53
- 125000000217 alkyl group Chemical group 0.000 claims description 48
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 35
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 33
- -1 nitro, difluoromethyl Chemical group 0.000 claims description 33
- 239000001257 hydrogen Substances 0.000 claims description 31
- 229910052739 hydrogen Inorganic materials 0.000 claims description 31
- 238000000034 method Methods 0.000 claims description 30
- 238000006243 chemical reaction Methods 0.000 claims description 26
- 239000003054 catalyst Substances 0.000 claims description 18
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
- 150000002431 hydrogen Chemical class 0.000 claims description 16
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- 239000012442 inert solvent Substances 0.000 claims description 15
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 15
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 14
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 14
- 125000003342 alkenyl group Chemical group 0.000 claims description 14
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 14
- 229910052794 bromium Inorganic materials 0.000 claims description 14
- 239000000460 chlorine Substances 0.000 claims description 14
- 229910052801 chlorine Inorganic materials 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 14
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 11
- 229910052731 fluorine Inorganic materials 0.000 claims description 10
- 239000011737 fluorine Substances 0.000 claims description 10
- 229920006395 saturated elastomer Polymers 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- 125000004450 alkenylene group Chemical group 0.000 claims description 7
- 125000002947 alkylene group Chemical group 0.000 claims description 7
- 201000010099 disease Diseases 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 7
- 230000002829 reductive effect Effects 0.000 claims description 7
- BSRHATGBRQMDRF-UHFFFAOYSA-N 3,4-dihydro-2h-chromen-2-ylmethanamine Chemical compound C1=CC=C2OC(CN)CCC2=C1 BSRHATGBRQMDRF-UHFFFAOYSA-N 0.000 claims description 6
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- 238000005932 reductive alkylation reaction Methods 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 5
- 125000004419 alkynylene group Chemical group 0.000 claims description 5
- 238000007796 conventional method Methods 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 125000006239 protecting group Chemical group 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 4
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 239000000969 carrier Substances 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 238000005984 hydrogenation reaction Methods 0.000 claims description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 claims description 2
- AQYSYJUIMQTRMV-UHFFFAOYSA-N hypofluorous acid Chemical compound FO AQYSYJUIMQTRMV-UHFFFAOYSA-N 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 125000005493 quinolyl group Chemical group 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 2
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 claims 1
- 230000002295 serotoninergic effect Effects 0.000 claims 1
- 230000029936 alkylation Effects 0.000 abstract description 5
- 238000005804 alkylation reaction Methods 0.000 abstract description 4
- 208000035475 disorder Diseases 0.000 abstract description 3
- 238000006268 reductive amination reaction Methods 0.000 abstract description 3
- 239000004480 active ingredient Substances 0.000 abstract description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 87
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 54
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 47
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 46
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 35
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 31
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- 239000000243 solution Substances 0.000 description 21
- 235000019441 ethanol Nutrition 0.000 description 20
- 239000000203 mixture Substances 0.000 description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 239000000741 silica gel Substances 0.000 description 16
- 229910002027 silica gel Inorganic materials 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
- 239000002585 base Substances 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 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 10
- 239000002904 solvent Substances 0.000 description 10
- 150000001408 amides Chemical class 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 235000011054 acetic acid Nutrition 0.000 description 8
- 229910052763 palladium Inorganic materials 0.000 description 8
- 150000003254 radicals Chemical class 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
- 150000001298 alcohols Chemical class 0.000 description 7
- 150000002170 ethers Chemical class 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
- 239000012458 free base Substances 0.000 description 6
- 150000004678 hydrides Chemical class 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 239000003960 organic solvent Substances 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 238000006722 reduction reaction Methods 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000002253 acid Substances 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical class B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 5
- 150000008282 halocarbons Chemical class 0.000 description 5
- 150000002576 ketones Chemical class 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 150000001735 carboxylic acids Chemical class 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 238000003818 flash chromatography Methods 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 3
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 3
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 229930040373 Paraformaldehyde Natural products 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 3
- 229940092714 benzenesulfonic acid Drugs 0.000 description 3
- 229910000085 borane Inorganic materials 0.000 description 3
- 244000309466 calf Species 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 239000003610 charcoal Substances 0.000 description 3
- 239000003638 chemical reducing agent 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
- 238000003776 cleavage reaction Methods 0.000 description 3
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 3
- CIYPNZYEUZQIHN-UHFFFAOYSA-N cycloheptanecarbonyl chloride Chemical compound ClC(=O)C1CCCCCC1 CIYPNZYEUZQIHN-UHFFFAOYSA-N 0.000 description 3
- 150000002081 enamines Chemical class 0.000 description 3
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 3
- 150000003840 hydrochlorides Chemical class 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 229940098779 methanesulfonic acid Drugs 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 239000002808 molecular sieve Substances 0.000 description 3
- 229920002866 paraformaldehyde Polymers 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 235000019260 propionic acid Nutrition 0.000 description 3
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 3
- 239000002287 radioligand Substances 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 108010085082 sigma receptors Proteins 0.000 description 3
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- RFKKWPUMWWARKM-UHFFFAOYSA-N (8-methoxy-3,4-dihydro-2h-chromen-2-yl)methanamine;hydrochloride Chemical compound Cl.C1CC(CN)OC2=C1C=CC=C2OC RFKKWPUMWWARKM-UHFFFAOYSA-N 0.000 description 2
- BGJSXRVXTHVRSN-UHFFFAOYSA-N 1,3,5-trioxane Chemical compound C1OCOCO1 BGJSXRVXTHVRSN-UHFFFAOYSA-N 0.000 description 2
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 2
- CXBDYQVECUFKRK-UHFFFAOYSA-N 1-methoxybutane Chemical compound CCCCOC CXBDYQVECUFKRK-UHFFFAOYSA-N 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 2
- QZZSXVDBAPRCRM-UHFFFAOYSA-N 3,4-dihydro-2h-chromen-2-ylmethylazanium;chloride Chemical compound Cl.C1=CC=C2OC(CN)CCC2=C1 QZZSXVDBAPRCRM-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C07D311/64—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with oxygen atoms directly attached in position 8
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrane Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Cosmetics (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Priority Applications (20)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4135474A DE4135474A1 (de) | 1991-10-28 | 1991-10-28 | 2-aminomethyl-chromane |
| TW081107544A TW207537B (https=) | 1991-10-28 | 1992-09-24 | |
| MX9205681A MX9205681A (es) | 1991-10-28 | 1992-10-05 | Aminometil-cromanos, procedimiento para su fabricacion y medicamento que los contiene. |
| AU26264/92A AU2626492A (en) | 1991-10-28 | 1992-10-07 | 2- aminomethyl-chromans |
| NO92923975A NO923975L (no) | 1991-10-28 | 1992-10-13 | 2-aminometyl-kromaner |
| EP92117605A EP0540914B1 (de) | 1991-10-28 | 1992-10-15 | 2-Aminomethyl-chromane als Wirkstoffe in Arzneimitteln zur Behandlung von Erkrankungen des Zentralnervensystems |
| AT92117605T ATE180777T1 (de) | 1991-10-28 | 1992-10-15 | 2-aminomethyl-chromane als wirkstoffe in arzneimitteln zur behandlung von erkrankungen des zentralnervensystems |
| ES92117605T ES2132105T3 (es) | 1991-10-28 | 1992-10-15 | 2-aminometil-cromanos como principios activos en farmacos para el tratamiento de enfermedades del sistema nervioso central. |
| DE59209704T DE59209704D1 (de) | 1991-10-28 | 1992-10-15 | 2-Aminomethyl-chromane als Wirkstoffe in Arzneimitteln zur Behandlung von Erkrankungen des Zentralnervensystems |
| US07/963,203 US5318988A (en) | 1991-10-28 | 1992-10-19 | 2-aminomethyl-chromans |
| CA002081300A CA2081300A1 (en) | 1991-10-28 | 1992-10-23 | 2-aminomethyl-chromans |
| CS923225A CZ322592A3 (en) | 1991-10-28 | 1992-10-26 | 2-aminomethyl-chromans |
| FI924847A FI924847L (fi) | 1991-10-28 | 1992-10-26 | 2-aminometyl-kromaner |
| IL103545A IL103545A0 (en) | 1991-10-28 | 1992-10-26 | 2-aminomethyl-chromans,their preparation and pharmaceutical compositions containing them |
| KR1019920019793A KR930007930A (ko) | 1991-10-28 | 1992-10-27 | 2-아미노메틸-크로만 |
| ZA928291A ZA928291B (en) | 1991-10-28 | 1992-10-27 | 2-aminomethyl-chromans. |
| JP31296592A JP3299321B2 (ja) | 1991-10-28 | 1992-10-28 | ２−アミノメチル−クロマン類 |
| HU9203383A HUT62875A (en) | 1991-10-28 | 1992-10-28 | Process for producing 2-aminomethyl chroman derivatives and pharmaceutical compositions comprising such compounds |
| US08/215,995 US5468882A (en) | 1991-10-28 | 1994-03-22 | 2-aminomethyl-chromans |
| US08/631,386 US5962513A (en) | 1991-10-28 | 1996-04-12 | 2-aminomethyl-chromans effective in the treatment of psychoses and depression |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4135474A DE4135474A1 (de) | 1991-10-28 | 1991-10-28 | 2-aminomethyl-chromane |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE4135474A1 true DE4135474A1 (de) | 1993-04-29 |
Family
ID=6443566
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE4135474A Withdrawn DE4135474A1 (de) | 1991-10-28 | 1991-10-28 | 2-aminomethyl-chromane |
| DE59209704T Expired - Fee Related DE59209704D1 (de) | 1991-10-28 | 1992-10-15 | 2-Aminomethyl-chromane als Wirkstoffe in Arzneimitteln zur Behandlung von Erkrankungen des Zentralnervensystems |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE59209704T Expired - Fee Related DE59209704D1 (de) | 1991-10-28 | 1992-10-15 | 2-Aminomethyl-chromane als Wirkstoffe in Arzneimitteln zur Behandlung von Erkrankungen des Zentralnervensystems |
Country Status (17)
| Country | Link |
|---|---|
| US (3) | US5318988A (https=) |
| EP (1) | EP0540914B1 (https=) |
| JP (1) | JP3299321B2 (https=) |
| KR (1) | KR930007930A (https=) |
| AT (1) | ATE180777T1 (https=) |
| AU (1) | AU2626492A (https=) |
| CA (1) | CA2081300A1 (https=) |
| CZ (1) | CZ322592A3 (https=) |
| DE (2) | DE4135474A1 (https=) |
| ES (1) | ES2132105T3 (https=) |
| FI (1) | FI924847L (https=) |
| HU (1) | HUT62875A (https=) |
| IL (1) | IL103545A0 (https=) |
| MX (1) | MX9205681A (https=) |
| NO (1) | NO923975L (https=) |
| TW (1) | TW207537B (https=) |
| ZA (1) | ZA928291B (https=) |
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| EP0707007A1 (en) * | 1994-10-14 | 1996-04-17 | MERCK PATENT GmbH | Amino(thio)ether derivatives as CNS active agents |
| EP0771801A1 (en) * | 1995-11-06 | 1997-05-07 | American Home Products Corporation | Chromane derivatives |
| WO1999026621A1 (de) * | 1997-11-24 | 1999-06-03 | Bayer Aktiengesellschaft | Verwendung von substituierten aminomethyl-chromanen zur verhinderung der neuronalen degeneration und zur förderung der neuronalen regeneration |
| WO1999029346A1 (de) * | 1997-12-09 | 1999-06-17 | Bayer Aktiengesellschaft | Pharmazeutische zusammensetzung zur behandlung von schlaganfall und schädel-hirn-trauma |
| CZ300544B6 (cs) * | 1998-12-17 | 2009-06-10 | Merck Patent Gmbh | Deriváty chromanu, zpusob jejich prípravy a použití jako meziproduktu pro syntézu léciv |
| US7662979B2 (en) | 2006-05-25 | 2010-02-16 | Wyeth | Oxindoledioxans, synthesis thereof, and intermediates thereto |
| US7872030B2 (en) | 2001-07-26 | 2011-01-18 | Merck Patent Gmbh | Use of 2-[5-(4-fluorophenyl)-3-pyridylmethylaminomethyl]-chromane and its physiologically acceptable salts |
| US7928128B2 (en) | 2000-03-10 | 2011-04-19 | Merck Patent Gesellschaft Mit Beschrankter Haftung | Use of(R)-(−) -2-[5-(4-fluorophenyl)-3-pyridylmethylaminomethyl]-chromane and its physiologically acceptable salts |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4135474A1 (de) * | 1991-10-28 | 1993-04-29 | Bayer Ag | 2-aminomethyl-chromane |
| GB9303340D0 (en) * | 1993-02-19 | 1993-04-07 | Smithkline Beecham Plc | Pharmaceuticals |
| US5541199A (en) * | 1995-06-02 | 1996-07-30 | American Home Products Corporation | Chroman-2-ylmethylamino derivatives |
| DE19522088A1 (de) * | 1995-06-19 | 1997-01-02 | Bayer Ag | Benzisothiazolyl-substituierte Aminomethylchromane |
| US5670667A (en) * | 1995-07-25 | 1997-09-23 | American Home Products Corporation | Chroman-2-ylmethylamino derivatives |
| US5663194A (en) * | 1995-07-25 | 1997-09-02 | Mewshaw; Richard E. | Chroman-2-ylmethylamino derivatives |
| US5684039A (en) * | 1995-07-25 | 1997-11-04 | American Home Products Corporation | Chroman-2-ylmethylamino derivatives |
| US5756532A (en) * | 1995-11-06 | 1998-05-26 | American Home Products Corporation | Aminomethyl-2 3 8 9-tetrahydro-7H-1 4-dioxino 2 3-E!-indol-8-ones and derivatives |
| DE69722020T2 (de) * | 1996-10-15 | 2004-01-22 | Wyeth | Azaheterocyclylmethyl-derivate von 2,3,8,9-tetrahydro-7h-1,4-dioxino[2,3-e]indol-8-on |
| US5869490A (en) * | 1996-10-15 | 1999-02-09 | American Home Products Corporation | Azaheterocyclymethyl derivatives of 2,3,8,9-tetrahydro-7h-1,4-dioxino (2,3-e) indol-8-one |
| US5750556A (en) * | 1996-10-30 | 1998-05-12 | American Home Products Corporation | 2-(aminomethyl)-3,4,7,9-tetrahydro-2H-pyrano- 2,3-E!indol-8-ones and derivatives |
| CN1265087A (zh) * | 1997-07-31 | 2000-08-30 | 杜邦药品公司 | 环丙基乙炔的制备方法 |
| FR2769629B1 (fr) * | 1997-10-09 | 1999-11-12 | Synthelabo | Derives de 8-azabicyclo[3.2.1]octane-3-methanamine, leur preparation et leur application en therapeutique |
| UA58476C2 (uk) * | 1997-10-09 | 2003-08-15 | Санофі-Сентелябо | Похідні 8-азабіцикло[3.2.1]октан-3-метанаміну, фармацевтична композиція та лікарський засіб |
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| DE10120619A1 (de) * | 2001-04-26 | 2002-10-31 | Merck Patent Gmbh | 2-(5-(4-Fluorphenyl)-3-pyridylmethylaminomethyl-chroman |
| US6627639B2 (en) | 2001-04-26 | 2003-09-30 | Wyeth | Uses for indoletetrahydropyridine derivatives of 2,3-dihydro-7H-[1,4]dioxino-[2,3-e]indole |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4321270A (en) * | 1981-01-29 | 1982-03-23 | E. R. Squibb & Sons, Inc. | Substituted chromans |
| EP0325964A1 (en) * | 1988-01-15 | 1989-08-02 | Abbott Laboratories | Aminomethyl-chroman and -thiochroman compounds |
| CA1337432C (en) * | 1988-03-23 | 1995-10-24 | Raymond M. Xhonneux | Method of lowering the blood pressure |
| DE3901814A1 (de) * | 1988-07-28 | 1990-02-01 | Bayer Ag | Substituierte aminomethylzetraline sowie ihre heterocyclischen analoga |
| CA2002649C (en) * | 1988-11-14 | 2000-06-06 | Margaret Petty | Cardioprotective tocopherol analogs |
| US5229398A (en) * | 1990-02-27 | 1993-07-20 | Adir Et Compagnie | Aminomethylpiperidine compounds |
| US5126367A (en) * | 1991-06-21 | 1992-06-30 | American Home Products Corporation | Psychotropic benzodioxan derivatives |
| DE4135474A1 (de) * | 1991-10-28 | 1993-04-29 | Bayer Ag | 2-aminomethyl-chromane |
-
1991
- 1991-10-28 DE DE4135474A patent/DE4135474A1/de not_active Withdrawn
-
1992
- 1992-09-24 TW TW081107544A patent/TW207537B/zh active
- 1992-10-05 MX MX9205681A patent/MX9205681A/es unknown
- 1992-10-07 AU AU26264/92A patent/AU2626492A/en not_active Abandoned
- 1992-10-13 NO NO92923975A patent/NO923975L/no unknown
- 1992-10-15 ES ES92117605T patent/ES2132105T3/es not_active Expired - Lifetime
- 1992-10-15 DE DE59209704T patent/DE59209704D1/de not_active Expired - Fee Related
- 1992-10-15 EP EP92117605A patent/EP0540914B1/de not_active Expired - Lifetime
- 1992-10-15 AT AT92117605T patent/ATE180777T1/de not_active IP Right Cessation
- 1992-10-19 US US07/963,203 patent/US5318988A/en not_active Expired - Lifetime
- 1992-10-23 CA CA002081300A patent/CA2081300A1/en not_active Abandoned
- 1992-10-26 CZ CS923225A patent/CZ322592A3/cs unknown
- 1992-10-26 FI FI924847A patent/FI924847L/fi unknown
- 1992-10-26 IL IL103545A patent/IL103545A0/xx unknown
- 1992-10-27 KR KR1019920019793A patent/KR930007930A/ko not_active Withdrawn
- 1992-10-27 ZA ZA928291A patent/ZA928291B/xx unknown
- 1992-10-28 HU HU9203383A patent/HUT62875A/hu unknown
- 1992-10-28 JP JP31296592A patent/JP3299321B2/ja not_active Expired - Fee Related
-
1994
- 1994-03-22 US US08/215,995 patent/US5468882A/en not_active Expired - Fee Related
-
1996
- 1996-04-12 US US08/631,386 patent/US5962513A/en not_active Expired - Fee Related
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2155753C2 (ru) * | 1994-10-14 | 2000-09-10 | Мерк Патент Гмбх | Производные амино(тио)эфиров, способы их получения, фармацевтическая композиция на их основе и способ ее получения |
| US5767132A (en) * | 1994-10-14 | 1998-06-16 | Merck Patent Gesellschaft Mit Beschrankter Haftung | Pyridyl chroman |
| EP1123933A1 (en) * | 1994-10-14 | 2001-08-16 | MERCK PATENT GmbH | 2-[5-(4-fluorophenyl)-3-pyridylmethylaminomethyl]chromane as CNS active agent |
| EP0707007A1 (en) * | 1994-10-14 | 1996-04-17 | MERCK PATENT GmbH | Amino(thio)ether derivatives as CNS active agents |
| EP0771801A1 (en) * | 1995-11-06 | 1997-05-07 | American Home Products Corporation | Chromane derivatives |
| US6235774B1 (en) | 1997-11-24 | 2001-05-22 | Bayer Aktiengesellschaft | Application of substituted aminomethyl chromans in order to prevent neural degeneration and to promote neural regeneration |
| WO1999026621A1 (de) * | 1997-11-24 | 1999-06-03 | Bayer Aktiengesellschaft | Verwendung von substituierten aminomethyl-chromanen zur verhinderung der neuronalen degeneration und zur förderung der neuronalen regeneration |
| US6331561B2 (en) | 1997-11-24 | 2001-12-18 | Bayer Aktiengesellschaft | Use of substituted amino-methyl-chromans for the prevention of neuronal degeneration and for the promotion of neuronal regeneration |
| WO1999029346A1 (de) * | 1997-12-09 | 1999-06-17 | Bayer Aktiengesellschaft | Pharmazeutische zusammensetzung zur behandlung von schlaganfall und schädel-hirn-trauma |
| CZ300544B6 (cs) * | 1998-12-17 | 2009-06-10 | Merck Patent Gmbh | Deriváty chromanu, zpusob jejich prípravy a použití jako meziproduktu pro syntézu léciv |
| US7928128B2 (en) | 2000-03-10 | 2011-04-19 | Merck Patent Gesellschaft Mit Beschrankter Haftung | Use of(R)-(−) -2-[5-(4-fluorophenyl)-3-pyridylmethylaminomethyl]-chromane and its physiologically acceptable salts |
| US7872030B2 (en) | 2001-07-26 | 2011-01-18 | Merck Patent Gmbh | Use of 2-[5-(4-fluorophenyl)-3-pyridylmethylaminomethyl]-chromane and its physiologically acceptable salts |
| US7662979B2 (en) | 2006-05-25 | 2010-02-16 | Wyeth | Oxindoledioxans, synthesis thereof, and intermediates thereto |
Also Published As
| Publication number | Publication date |
|---|---|
| FI924847A7 (fi) | 1993-04-29 |
| FI924847L (fi) | 1993-04-29 |
| ES2132105T3 (es) | 1999-08-16 |
| ATE180777T1 (de) | 1999-06-15 |
| NO923975L (no) | 1993-04-29 |
| EP0540914B1 (de) | 1999-06-02 |
| TW207537B (https=) | 1993-06-11 |
| AU2626492A (en) | 1993-04-29 |
| CA2081300A1 (en) | 1993-04-29 |
| NO923975D0 (no) | 1992-10-13 |
| US5318988A (en) | 1994-06-07 |
| JPH05194473A (ja) | 1993-08-03 |
| US5962513A (en) | 1999-10-05 |
| MX9205681A (es) | 1993-04-01 |
| JP3299321B2 (ja) | 2002-07-08 |
| EP0540914A1 (de) | 1993-05-12 |
| KR930007930A (ko) | 1993-05-20 |
| HU9203383D0 (en) | 1993-01-28 |
| HUT62875A (en) | 1993-06-28 |
| IL103545A0 (en) | 1993-03-15 |
| FI924847A0 (fi) | 1992-10-26 |
| DE59209704D1 (de) | 1999-07-08 |
| CZ322592A3 (en) | 1993-05-12 |
| ZA928291B (en) | 1993-05-06 |
| US5468882A (en) | 1995-11-21 |
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