SK283517B6 - Heteroarylpiperidíny, heteroarylpyrolidíny a heteroarylpiperazíny, farmaceutické prostriedky, ktoré ich obsahujú, a ich použitie - Google Patents
Heteroarylpiperidíny, heteroarylpyrolidíny a heteroarylpiperazíny, farmaceutické prostriedky, ktoré ich obsahujú, a ich použitie Download PDFInfo
- Publication number
- SK283517B6 SK283517B6 SK456-94A SK45694A SK283517B6 SK 283517 B6 SK283517 B6 SK 283517B6 SK 45694 A SK45694 A SK 45694A SK 283517 B6 SK283517 B6 SK 283517B6
- Authority
- SK
- Slovakia
- Prior art keywords
- group
- formula
- alkyl
- fluoro
- piperidinyl
- Prior art date
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- 239000008194 pharmaceutical composition Substances 0.000 title claims description 9
- 150000004885 piperazines Chemical class 0.000 title abstract description 8
- 150000003235 pyrrolidines Chemical class 0.000 title abstract description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 164
- 230000000561 anti-psychotic effect Effects 0.000 claims abstract description 9
- 208000028017 Psychotic disease Diseases 0.000 claims abstract description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 252
- -1 nitro, amino Chemical group 0.000 claims description 144
- 125000003545 alkoxy group Chemical group 0.000 claims description 107
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 98
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 96
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 93
- 229910052739 hydrogen Inorganic materials 0.000 claims description 91
- 125000004432 carbon atom Chemical group C* 0.000 claims description 90
- 239000001257 hydrogen Substances 0.000 claims description 90
- 150000003839 salts Chemical class 0.000 claims description 87
- 125000003118 aryl group Chemical group 0.000 claims description 81
- 239000002253 acid Substances 0.000 claims description 78
- 229910052757 nitrogen Inorganic materials 0.000 claims description 72
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 69
- 229910052731 fluorine Inorganic materials 0.000 claims description 65
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 63
- 150000002431 hydrogen Chemical class 0.000 claims description 60
- 229910052717 sulfur Inorganic materials 0.000 claims description 59
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 59
- 229910052801 chlorine Inorganic materials 0.000 claims description 57
- 239000000460 chlorine Substances 0.000 claims description 56
- 239000011737 fluorine Substances 0.000 claims description 56
- 229910052794 bromium Inorganic materials 0.000 claims description 55
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 53
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 51
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 48
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 46
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 43
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 41
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 40
- 125000004434 sulfur atom Chemical group 0.000 claims description 39
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 37
- 125000002252 acyl group Chemical group 0.000 claims description 37
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 37
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 34
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 29
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 28
- 125000005843 halogen group Chemical group 0.000 claims description 26
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 25
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
- 229910052736 halogen Inorganic materials 0.000 claims description 23
- 150000002367 halogens Chemical class 0.000 claims description 23
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 23
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
- 229910052760 oxygen Inorganic materials 0.000 claims description 20
- 125000001424 substituent group Chemical group 0.000 claims description 20
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 19
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 19
- 125000004442 acylamino group Chemical group 0.000 claims description 18
- 125000001072 heteroaryl group Chemical group 0.000 claims description 18
- 229910052740 iodine Inorganic materials 0.000 claims description 18
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 17
- 125000004414 alkyl thio group Chemical group 0.000 claims description 17
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 17
- 238000002360 preparation method Methods 0.000 claims description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 16
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 16
- 125000001153 fluoro group Chemical group F* 0.000 claims description 15
- 125000003277 amino group Chemical group 0.000 claims description 13
- 125000003435 aroyl group Chemical group 0.000 claims description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
- 125000003386 piperidinyl group Chemical group 0.000 claims description 12
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 12
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 10
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 10
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 10
- 125000004193 piperazinyl group Chemical group 0.000 claims description 10
- 239000011593 sulfur Chemical group 0.000 claims description 10
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 9
- 125000001589 carboacyl group Chemical group 0.000 claims description 9
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 9
- 230000003287 optical effect Effects 0.000 claims description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 8
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 8
- 125000002757 morpholinyl group Chemical group 0.000 claims description 8
- 239000001301 oxygen Substances 0.000 claims description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
- 125000004429 atom Chemical group 0.000 claims description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- UMNKDRAGADXPKA-UHFFFAOYSA-N 3-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]propan-1-ol Chemical compound C1CN(CCCO)CCC1C1=NOC2=CC(F)=CC=C12 UMNKDRAGADXPKA-UHFFFAOYSA-N 0.000 claims description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 5
- 150000001735 carboxylic acids Chemical class 0.000 claims description 5
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 5
- 239000011630 iodine Substances 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims description 4
- 101150065749 Churc1 gene Proteins 0.000 claims description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- 102100038239 Protein Churchill Human genes 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- 229910021529 ammonia Inorganic materials 0.000 claims description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 claims description 4
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 4
- 150000007513 acids Chemical class 0.000 claims description 3
- 230000000202 analgesic effect Effects 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 3
- 239000011707 mineral Substances 0.000 claims description 3
- FPUDFDKQGXUBJA-UHFFFAOYSA-N n-[1-[4-[3-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]propoxy]-3-methoxyphenyl]ethylidene]hydroxylamine Chemical compound COC1=CC(C(C)=NO)=CC=C1OCCCN1CCC(C=2C3=CC=C(F)C=C3ON=2)CC1 FPUDFDKQGXUBJA-UHFFFAOYSA-N 0.000 claims description 3
- 235000019260 propionic acid Nutrition 0.000 claims description 3
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 claims description 2
- XHLHPRDBBAGVEG-UHFFFAOYSA-N 1-tetralone Chemical compound C1=CC=C2C(=O)CCCC2=C1 XHLHPRDBBAGVEG-UHFFFAOYSA-N 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- 239000004135 Bone phosphate Substances 0.000 claims description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
- 125000004423 acyloxy group Chemical group 0.000 claims description 2
- 125000005466 alkylenyl group Chemical group 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000002346 iodo group Chemical group I* 0.000 claims description 2
- 229910017604 nitric acid Inorganic materials 0.000 claims description 2
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims description 2
- 125000006308 propyl amino group Chemical group 0.000 claims description 2
- 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 claims description 2
- 229930195734 saturated hydrocarbon Natural products 0.000 claims description 2
- RGXWDWUGBIJHDO-UHFFFAOYSA-N ethyl decanoate Chemical compound CCCCCCCCCC(=O)OCC RGXWDWUGBIJHDO-UHFFFAOYSA-N 0.000 claims 2
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
- MDVOAKSPEFVXPL-UHFFFAOYSA-N 1-[4-[3-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]propylamino]-3-methoxyphenyl]ethanone Chemical compound COC1=CC(C(C)=O)=CC=C1NCCCN1CCC(C=2C3=CC=C(F)C=C3ON=2)CC1 MDVOAKSPEFVXPL-UHFFFAOYSA-N 0.000 claims 1
- LMFSAUMXPCITAG-UHFFFAOYSA-N 1-[4-[3-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]propylsulfanyl]-3-methoxyphenyl]ethanone Chemical compound COC1=CC(C(C)=O)=CC=C1SCCCN1CCC(C=2C3=CC=C(F)C=C3ON=2)CC1 LMFSAUMXPCITAG-UHFFFAOYSA-N 0.000 claims 1
- FDAOKFMMTDFDFV-UHFFFAOYSA-N 2-[2-[4-(6-fluoro-1,2-benzothiazol-3-yl)piperidin-1-yl]ethyl]isoindole-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1CCN(CC1)CCC1C1=NSC2=CC(F)=CC=C21 FDAOKFMMTDFDFV-UHFFFAOYSA-N 0.000 claims 1
- SABLNKQQFXIZLO-UHFFFAOYSA-N 2-[2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl]isoindole-1,3-dione;hydrochloride Chemical compound Cl.O=C1C2=CC=CC=C2C(=O)N1CCN(CC1)CCC1C1=NOC2=CC(F)=CC=C21 SABLNKQQFXIZLO-UHFFFAOYSA-N 0.000 claims 1
- BNNPIHSALAAOTA-UHFFFAOYSA-N 3-(1-benzylpyrrolidin-3-yl)-6-fluoro-1,2-benzoxazole Chemical compound N=1OC2=CC(F)=CC=C2C=1C(C1)CCN1CC1=CC=CC=C1 BNNPIHSALAAOTA-UHFFFAOYSA-N 0.000 claims 1
- MBOHAKIIZHMYHZ-UHFFFAOYSA-N 3-[1-[2-(1,3-dioxan-2-yl)ethyl]piperidin-4-yl]-6-fluoro-1,2-benzoxazole Chemical compound N=1OC2=CC(F)=CC=C2C=1C(CC1)CCN1CCC1OCCCO1 MBOHAKIIZHMYHZ-UHFFFAOYSA-N 0.000 claims 1
- WHKYLOYLIOLDFP-UHFFFAOYSA-N 4-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]butan-1-ol Chemical compound C1CN(CCCCO)CCC1C1=NOC2=CC(F)=CC=C12 WHKYLOYLIOLDFP-UHFFFAOYSA-N 0.000 claims 1
- AVGMYGKFQJVAEP-UHFFFAOYSA-N 4-fluoro-2-[2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl]isoindole-1,3-dione Chemical compound O=C1C2=CC=CC(F)=C2C(=O)N1CCN(CC1)CCC1C1=NOC2=CC(F)=CC=C21 AVGMYGKFQJVAEP-UHFFFAOYSA-N 0.000 claims 1
- FHHRGSQLYRCKOF-UHFFFAOYSA-N 5-fluoro-2-[2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl]isoindole-1,3-dione Chemical compound FC1=CC=C2C(C3CCN(CC3)CCN3C(=O)C4=CC=C(C=C4C3=O)F)=NOC2=C1 FHHRGSQLYRCKOF-UHFFFAOYSA-N 0.000 claims 1
- PTRAONPJZIRTKF-UHFFFAOYSA-N 6-fluoro-3-[1-(3-pyrimidin-2-yloxypropyl)piperidin-4-yl]-1,2-benzoxazole Chemical compound N=1OC2=CC(F)=CC=C2C=1C(CC1)CCN1CCCOC1=NC=CC=N1 PTRAONPJZIRTKF-UHFFFAOYSA-N 0.000 claims 1
- ZYEMHLKWOLZWOA-UHFFFAOYSA-N 6-fluoro-3-[1-[3-[(6-methoxy-1h-indol-5-yl)oxy]propyl]piperidin-4-yl]-1,2-benzoxazole Chemical compound FC1=CC=C2C(C3CCN(CC3)CCCOC3=CC=4C=CNC=4C=C3OC)=NOC2=C1 ZYEMHLKWOLZWOA-UHFFFAOYSA-N 0.000 claims 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims 1
- LPQOADBMXVRBNX-UHFFFAOYSA-N ac1ldcw0 Chemical compound Cl.C1CN(C)CCN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN3CCSC1=C32 LPQOADBMXVRBNX-UHFFFAOYSA-N 0.000 claims 1
- 150000003863 ammonium salts Chemical class 0.000 claims 1
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 claims 1
- 125000002837 carbocyclic group Chemical group 0.000 claims 1
- 239000004927 clay Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 125000004464 hydroxyphenyl group Chemical group 0.000 claims 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims 1
- 239000011976 maleic acid Substances 0.000 claims 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 1
- 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 claims 1
- 239000001384 succinic acid Substances 0.000 claims 1
- 239000000164 antipsychotic agent Substances 0.000 abstract description 7
- 239000000730 antalgic agent Substances 0.000 abstract description 6
- 229940035676 analgesics Drugs 0.000 abstract description 5
- 241000124008 Mammalia Species 0.000 abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 426
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 278
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 261
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 222
- 239000007787 solid Substances 0.000 description 190
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 184
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 177
- 239000000203 mixture Substances 0.000 description 173
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 173
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 143
- 239000011541 reaction mixture Substances 0.000 description 123
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 115
- 238000004458 analytical method Methods 0.000 description 106
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 93
- 229910000027 potassium carbonate Inorganic materials 0.000 description 92
- 238000010992 reflux Methods 0.000 description 86
- 239000000243 solution Substances 0.000 description 83
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 73
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 66
- 239000000741 silica gel Substances 0.000 description 63
- 229910002027 silica gel Inorganic materials 0.000 description 63
- 239000002904 solvent Substances 0.000 description 63
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 57
- 235000019341 magnesium sulphate Nutrition 0.000 description 57
- 239000000047 product Substances 0.000 description 55
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 54
- 239000003921 oil Substances 0.000 description 53
- 239000013078 crystal Substances 0.000 description 51
- 238000006243 chemical reaction Methods 0.000 description 48
- 239000003480 eluent Substances 0.000 description 48
- 238000001953 recrystallisation Methods 0.000 description 44
- 238000003818 flash chromatography Methods 0.000 description 41
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 39
- 239000000463 material Substances 0.000 description 39
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
- MRMGJMGHPJZSAE-UHFFFAOYSA-N 6-fluoro-3-piperidin-4-yl-1,2-benzoxazole Chemical compound N=1OC2=CC(F)=CC=C2C=1C1CCNCC1 MRMGJMGHPJZSAE-UHFFFAOYSA-N 0.000 description 37
- 239000000126 substance Substances 0.000 description 36
- 239000002024 ethyl acetate extract Substances 0.000 description 32
- 239000003643 water by type Substances 0.000 description 31
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- 239000000706 filtrate Substances 0.000 description 30
- 239000000523 sample Substances 0.000 description 27
- 239000000284 extract Substances 0.000 description 24
- 239000012267 brine Substances 0.000 description 23
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 23
- 239000012258 stirred mixture Substances 0.000 description 22
- 239000000725 suspension Substances 0.000 description 20
- 239000012299 nitrogen atmosphere Substances 0.000 description 19
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
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- SNMVRZFUUCLYTO-UHFFFAOYSA-N n-propyl chloride Chemical compound CCCCl SNMVRZFUUCLYTO-UHFFFAOYSA-N 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- 239000000346 nonvolatile oil Substances 0.000 description 1
- 238000007344 nucleophilic reaction Methods 0.000 description 1
- 125000002801 octanoyl group Chemical group C(CCCCCCC)(=O)* 0.000 description 1
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- XNLICIUVMPYHGG-UHFFFAOYSA-N pentan-2-one Chemical compound CCCC(C)=O XNLICIUVMPYHGG-UHFFFAOYSA-N 0.000 description 1
- VOKSWYLNZZRQPF-GDIGMMSISA-N pentazocine Chemical compound C1C2=CC=C(O)C=C2[C@@]2(C)[C@@H](C)[C@@H]1N(CC=C(C)C)CC2 VOKSWYLNZZRQPF-GDIGMMSISA-N 0.000 description 1
- 229960005301 pentazocine Drugs 0.000 description 1
- 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
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
- OHEDMAIVEXQCOZ-UHFFFAOYSA-N piperidine;dihydrochloride Chemical compound Cl.Cl.C1CCNCC1 OHEDMAIVEXQCOZ-UHFFFAOYSA-N 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical class [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- ZLMJMSJWJFRBEC-OUBTZVSYSA-N potassium-40 Chemical compound [40K] ZLMJMSJWJFRBEC-OUBTZVSYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 238000006748 scratching Methods 0.000 description 1
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- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- SYXYWTXQFUUWLP-UHFFFAOYSA-N sodium;butan-1-olate Chemical compound [Na+].CCCC[O-] SYXYWTXQFUUWLP-UHFFFAOYSA-N 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 229960004940 sulpiride Drugs 0.000 description 1
- 239000010414 supernatant solution Substances 0.000 description 1
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Classifications
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A—HUMAN NECESSITIES
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- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/16—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
- C07C233/24—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
- C07C233/25—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
-
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/30—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by doubly-bound oxygen atoms
- C07C233/33—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by doubly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/54—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and etherified hydroxy groups bound to the carbon skeleton
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/22—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and doubly-bound oxygen atoms bound to the same carbon skeleton
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- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
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- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/673—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by change of size of the carbon skeleton
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- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C45/70—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form
- C07C45/71—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form being hydroxy groups
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- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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 radicals, substituted by hetero atoms, attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/20—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings condensed with carbocyclic rings or ring systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/04—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems
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- C—CHEMISTRY; METALLURGY
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- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/04—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems
- C07D275/06—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings condensed with carbocyclic rings or ring systems with hetero atoms directly attached to the ring sulfur atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D277/82—Nitrogen atoms
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
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- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pain & Pain Management (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Rheumatology (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US78826991A | 1991-11-05 | 1991-11-05 | |
US07/969,383 US5364866A (en) | 1989-05-19 | 1992-10-30 | Heteroarylpiperidines, pyrrolidines and piperazines and their use as antipsychotics and analetics |
PCT/US1992/009276 WO1993009102A1 (fr) | 1991-11-05 | 1992-11-04 | Heteroarylpiperidines, pyrrolidines et piperazines ainsi que leur utilisation comme agents neuroleptiques et analgesiques |
Publications (2)
Publication Number | Publication Date |
---|---|
SK45694A3 SK45694A3 (en) | 1995-02-08 |
SK283517B6 true SK283517B6 (sk) | 2003-08-05 |
Family
ID=27120778
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SK456-94A SK283517B6 (sk) | 1991-11-05 | 1992-11-04 | Heteroarylpiperidíny, heteroarylpyrolidíny a heteroarylpiperazíny, farmaceutické prostriedky, ktoré ich obsahujú, a ich použitie |
Country Status (25)
Country | Link |
---|---|
US (4) | US5364866A (fr) |
EP (8) | EP0959076B1 (fr) |
JP (1) | JP2927551B2 (fr) |
KR (1) | KR100276764B1 (fr) |
AT (3) | ATE248825T1 (fr) |
AU (1) | AU674499B2 (fr) |
CA (1) | CA2121253C (fr) |
CZ (1) | CZ287611B6 (fr) |
DE (3) | DE69233189T2 (fr) |
DK (3) | DK0612318T3 (fr) |
ES (3) | ES2283087T3 (fr) |
FI (2) | FI942052A (fr) |
GE (1) | GEP19991706B (fr) |
HK (2) | HK1023776A1 (fr) |
HU (1) | HUT70855A (fr) |
IL (1) | IL103622A (fr) |
NO (1) | NO304979B1 (fr) |
NZ (1) | NZ245006A (fr) |
PH (1) | PH30432A (fr) |
PT (2) | PT963984E (fr) |
RO (1) | RO114447B1 (fr) |
RU (1) | RU2127731C1 (fr) |
SK (1) | SK283517B6 (fr) |
UA (1) | UA41289C2 (fr) |
WO (1) | WO1993009102A1 (fr) |
Families Citing this family (69)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5776963A (en) * | 1989-05-19 | 1998-07-07 | Hoechst Marion Roussel, Inc. | 3-(heteroaryl)-1- (2,3-dihydro-1h-isoindol-2-yl)alkyl!pyrrolidines and 3-(heteroaryl)-1- (2,3-dihydro-1h-indol-1-yl)alkyl!pyrrolidines and related compounds and their therapeutic untility |
US5561128A (en) * | 1989-05-19 | 1996-10-01 | Hoechst-Roussel Pharmaceuticals, Inc. | N-[(4-(heteroaryl)-1-piperidinyl)alkyl]-10,11-dihydro-5H-dibenz[B,F]azepines and related compounds and their therapeutic utility |
US5364866A (en) | 1989-05-19 | 1994-11-15 | Hoechst-Roussel Pharmaceuticals, Inc. | Heteroarylpiperidines, pyrrolidines and piperazines and their use as antipsychotics and analetics |
US5750542A (en) * | 1993-09-28 | 1998-05-12 | Pfizer | Benzisoxazole and benzisothizole derivatives as cholinesterase inhibitors |
US5494908A (en) * | 1992-11-23 | 1996-02-27 | Hoechst-Roussel Pharmaceutical Incorporated | Substituted 3-(aminoalkylamino)-1,2-benzisoxazoles and related compounds |
JP3462501B2 (ja) * | 1992-11-23 | 2003-11-05 | アベンティス・ファーマスーティカルズ・インコーポレイテツド | 置換された3−(アミノアルキルアミノ)−1,2−ベンゾイソキサゾールおよび関連化合物 |
GB9410031D0 (en) * | 1994-05-19 | 1994-07-06 | Merck Sharp & Dohme | Therapeutic agents |
HUP9802492A3 (en) * | 1995-06-06 | 1999-10-28 | Hoechst Marion Roussel Inc Cin | Benzisoxazole and indazole derivatives as antipsychotic agents, process for their preparation and pharmaceutical compositions containing the same |
KR100539030B1 (ko) * | 1996-08-12 | 2005-12-27 | 셀진 코포레이션 | 면역치료제 및 이를 이용하여 사이토카인 농도를 감소시키는 방법 |
GB0117577D0 (en) | 2001-02-16 | 2001-09-12 | Aventis Pharm Prod Inc | Novel heterocyclic substituted carbonyl derivatives and their use as dopamine D receptor ligands |
DE60208157T2 (de) * | 2001-02-16 | 2006-08-10 | Aventis Pharmaceuticals Inc. | Heterocyclische substituierte carbonyl derivate und ihre verwendung als dopamin d3 rezeptor liganden |
FR2827280B1 (fr) * | 2001-07-13 | 2003-10-31 | Servier Lab | Nouveaux derives de benzene sulfonamide, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
ES2398434T3 (es) | 2001-08-31 | 2013-03-19 | Novartis Ag | Isómeros ópticos de un metabolito de iloperidona |
US7355042B2 (en) * | 2001-10-16 | 2008-04-08 | Hypnion, Inc. | Treatment of CNS disorders using CNS target modulators |
DE60238780D1 (de) * | 2001-10-30 | 2011-02-10 | Novartis Ag | Depot formulierungen von iloperidone und einem sternförmigen polymer |
CA2476936A1 (fr) * | 2002-02-20 | 2003-08-28 | Chih-Hung Lee | Composes azabicycliques fusionnes qui inhibent le recepteur (vr1) sous-type 1 du recepteur vanilloide |
GB0216416D0 (en) | 2002-07-15 | 2002-08-21 | Novartis Ag | Organic compounds |
US6939877B2 (en) * | 2002-09-12 | 2005-09-06 | Wyeth | Antidepressant piperidine derivatives of heterocycle-fused benzodioxans |
PL375981A1 (en) * | 2002-09-17 | 2005-12-12 | Warner-Lambert Company Llc | Heterocyclic substituted piperazines for the treatment of schizophrenia |
CA2500115A1 (fr) * | 2002-09-26 | 2004-04-08 | Warner-Lambert Company Llc | Piperazines substituees heterocycliques destinees au traitement de la schizophrenie |
US7157471B2 (en) * | 2003-08-25 | 2007-01-02 | Boehringer Ingelheim International Gmbh | Haloalkyl- and piperidine-substituted benzimidazole-derivatives |
GB0322994D0 (en) * | 2003-10-01 | 2003-11-05 | Novartis Ag | Organic compounds |
BRPI0416739A (pt) * | 2003-12-08 | 2007-01-16 | Warner Lambert Co | derivados de indano substituìdo heterocìclico e compostos afins para o tratamento de esquizofrenia |
CA3113166A1 (fr) | 2004-09-30 | 2006-04-13 | Vanda Pharmaceuticals Inc. | Methodes d'administration d'iloperidone |
US20100063093A1 (en) | 2007-03-28 | 2010-03-11 | Curt Wolfgang | Methods for the administration of iloperidone |
DE602006012650D1 (de) * | 2005-04-26 | 2010-04-15 | Hypnion Inc | Benzisoxazolpiperidinverbindungen und verfahren zu deren anwendung |
CA2637531A1 (fr) * | 2006-02-17 | 2007-08-30 | Memory Pharmaceuticals Corporation | Composes ayant une affinite pour le recepteur 5-ht6 |
KR20090029200A (ko) * | 2006-05-22 | 2009-03-20 | 반다 파마슈티칼즈, 인코퍼레이티드. | 우울증 질환에 대한 치료 |
US20150259747A1 (en) | 2007-03-29 | 2015-09-17 | Vanda Pharmaceuticals Inc. | Method of predicting a predisposition to qt prolongation |
WO2008121899A2 (fr) | 2007-03-29 | 2008-10-09 | Vanda Pharmaceuticals Inc. | Procédé permettant de prédire une prédisposition à la prolongation du qt |
US8198305B2 (en) * | 2007-04-13 | 2012-06-12 | Concert Pharmaceuticals Inc. | 1,2-benzisoxazol-3-yl compounds |
WO2008144599A2 (fr) | 2007-05-18 | 2008-11-27 | Vanda Pharmaceuticals Inc. | Marqueurs génétiques d'efficacité de l'ilopéridone dans le traitement de symptômes psychotiques |
EP2183245B1 (fr) * | 2007-07-26 | 2014-07-09 | F. Hoffmann-La Roche AG | Modulateurs doubles de récepteurs 5-ht2a et d3 |
KR20100053626A (ko) * | 2007-08-15 | 2010-05-20 | 메모리 파마슈티칼스 코포레이션 | 5-ht6 수용체 친화성을 나타내는 3'-치환된 화합물 |
US8652776B2 (en) * | 2007-09-10 | 2014-02-18 | Vanda Pharmaceuticals, Inc. | Prediction of QT prolongation based on SNP genotype |
WO2009076664A1 (fr) | 2007-12-13 | 2009-06-18 | Vanda Pharmaceuticals Inc. | Procédé et composition pour traiter une affection véhiculée par récepteur de la sérotonine |
ES2527515T3 (es) | 2007-12-13 | 2015-01-26 | Vanda Pharmaceuticals Inc. | Método y composición para tratar una afección mediada por un adrenoceptor alfa |
US20100016297A1 (en) * | 2008-06-24 | 2010-01-21 | Memory Pharmaceuticals Corporation | Alkyl-substituted 3' compounds having 5-ht6 receptor affinity |
US20100029629A1 (en) * | 2008-07-25 | 2010-02-04 | Memory Pharmaceuticals Corporation | Acyclic compounds having 5-ht6 receptor affinity |
US20100056531A1 (en) * | 2008-08-22 | 2010-03-04 | Memory Pharmaceuticals Corporation | Alkyl-substituted 3' compounds having 5-ht6 receptor affinity |
US9074255B2 (en) | 2009-04-06 | 2015-07-07 | Vanda Pharmaceuticals, Inc. | Method of predicting a predisposition to QT prolongation |
WO2010117943A1 (fr) | 2009-04-06 | 2010-10-14 | Vanda Pharmaceuticals, Inc. | Procédé de prédiction d'une prédisposition à une prolongation de qt sur la base d'une séquence de gène bai3 ou d'un produit de celle-ci |
EP2416778B1 (fr) | 2009-04-06 | 2016-03-02 | Vanda Pharmaceuticals Inc. | Procede de prediction de la predisposition a une elongation de l'interval qt base sur le gene abcc2 ou de ces produits |
HUE037724T2 (hu) | 2009-04-06 | 2018-09-28 | Vanda Pharmaceuticals Inc | Eljárás a KCNQ1 gén polimorfizmusán alapuló kezelésre |
DE102009016996A1 (de) | 2009-04-08 | 2010-10-14 | Fleissner Gmbh | Vorrichtung zum Verfestigen einer Faserbahn |
DE102009017729A1 (de) | 2009-04-11 | 2010-10-14 | Fleissner Gmbh | Vorrichtung zum Verfestigen einer Faserbahn |
DE102009032343A1 (de) | 2009-07-09 | 2011-01-20 | Fleissner Gmbh Und Co. | Vorrichtung zum Verfestigen einer Materialbahn |
CN102395582A (zh) * | 2009-09-19 | 2012-03-28 | 浙江华海药业股份有限公司 | 伊潘立酮的一种制备方法及结晶方法 |
WO2011055188A1 (fr) * | 2009-11-05 | 2011-05-12 | Orchid Chemicals And Pharmaceuticals Limited | Amélioration de procédé d'élaboration d'ilopéridone |
WO2011061750A2 (fr) * | 2009-11-19 | 2011-05-26 | Symed Labs Limited | Procédé pour la préparation d'ilopéridone à l'aide d'un nouvel intermédiaire |
WO2011077239A2 (fr) | 2009-12-23 | 2011-06-30 | Lupin Limited | Compositions pharmaceutiques d'ilopéridone à libération lente |
AU2010339689B2 (en) | 2010-01-07 | 2015-02-19 | Alkermes Pharma Ireland Limited | Quaternary ammonium salt prodrugs |
US8343706B2 (en) * | 2010-01-25 | 2013-01-01 | International Business Machines Corporation | Fluorine-free fused ring heteroaromatic photoacid generators and resist compositions containing the same |
DE102010009275A1 (de) | 2010-02-25 | 2011-08-25 | Trützschler Nonwovens GmbH, 63329 | Vorrichtung zum Verfestigen einer Materialbahn |
WO2011154860A1 (fr) * | 2010-06-08 | 2011-12-15 | Alembic Pharmaceuticals Limited | Procédé amélioré pour la préparation de l'ilopéridone |
US9000221B2 (en) * | 2010-09-07 | 2015-04-07 | Symed Labs Limited | Processes for the preparation of 4′-[3-[4-(6-Fluoro-1 ,2-benzisoxazol-3-yl)piperidino]propoxy]-3′-methoxyacetophenone and intermediates thereof |
WO2012090138A1 (fr) * | 2010-12-27 | 2012-07-05 | Ranbaxy Laboratories Limited | Procédés de synthèse de l'ilopéridone |
WO2012123963A2 (fr) | 2011-02-24 | 2012-09-20 | Megafine Pharma (P) Ltd. | Procédé pour la préparation d'ilopéridone et de coprécipité amorphe d'ilopéridone avec un excipient pharmaceutiquement acceptable |
US10874659B2 (en) | 2012-03-14 | 2020-12-29 | Vanda Pharmaceuticals Inc. | Iloperidone metabolite for use in the treatment of psychiatric disorders |
US9375433B2 (en) * | 2012-09-26 | 2016-06-28 | Tangent Reprofiling Limited | Modulators of androgen synthesis |
EP2919788A4 (fr) | 2012-11-14 | 2016-05-25 | Univ Johns Hopkins | Méthodes et compositions pour le traitement de la schizophrénie |
CN103012387B (zh) * | 2012-12-26 | 2015-08-12 | 浙江大学 | 伊潘立酮的制备方法 |
EP2968237A4 (fr) | 2013-03-15 | 2016-08-31 | Univ Johns Hopkins | Procédés et compositions pour améliorer la fonction cognitive |
DK2968220T3 (da) | 2013-03-15 | 2021-06-14 | Agenebio Inc | Fremgangsmåder og sammensætninger til forbedring af kognitiv funktion |
CN103319472B (zh) * | 2013-07-23 | 2016-07-06 | 河北科技大学 | 一种伊潘立酮的制备方法 |
BR112017025031B1 (pt) | 2015-05-22 | 2023-03-21 | Agenebio, Inc | Composições farmacêuticas de liberação prolongada de levetiracetam |
JP7532367B2 (ja) | 2018-12-04 | 2024-08-13 | バンダ・ファーマシューティカルズ・インコーポレイテッド | イロペリドンの持効性投与 |
US11607408B2 (en) | 2019-10-15 | 2023-03-21 | Vanda Pharmaceuticals Inc. | Method of treatment of schizophrenia |
WO2023201182A1 (fr) | 2022-04-13 | 2023-10-19 | Vanda Pharmaceuticals Inc. | Traitement de la maladie de parkinson et de la psychose de la maladie de parkinson |
Family Cites Families (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2258843B1 (fr) * | 1974-01-30 | 1977-09-09 | Roussel Uclaf | |
US4335127A (en) * | 1979-01-08 | 1982-06-15 | Janssen Pharmaceutica, N.V. | Piperidinylalkyl quinazoline compounds, composition and method of use |
US4355037A (en) * | 1981-11-12 | 1982-10-19 | Hoechst-Roussel Pharmaceuticals | 3-(4-Piperidyl)-1,2-benzisoxales |
US4458076A (en) * | 1983-05-31 | 1984-07-03 | Hoechst-Roussel Pharmaceuticals | 3-(4-Piperidinyl)-1,2-benzisothiazoles |
US4670447A (en) * | 1983-08-22 | 1987-06-02 | Hoechst-Roussel Pharmaceuticals Inc. | Antipsychotic 3-(piperidinyl)- and 3-(pyrrolidinyl)-1H-indazoles |
HU198036B (en) * | 1983-08-22 | 1989-07-28 | Hoechst Roussel Pharma | Process for production of derivatives of 3-piperidil-/1h/-indasole and medical preparatives containing them |
US4590196A (en) * | 1984-08-23 | 1986-05-20 | Bristol-Myers Company | Analgesic 1,2-benzisothiazol-3-ylpiperazine derivatives |
JPH0625181B2 (ja) | 1985-03-27 | 1994-04-06 | 住友製薬株式会社 | 新規なイミド誘導体 |
JP2660407B2 (ja) * | 1986-09-26 | 1997-10-08 | 住友製薬株式会社 | 新規なイミド誘導体 |
EP0302423A3 (fr) | 1987-08-07 | 1991-01-09 | Hoechst-Roussel Pharmaceuticals Incorporated | Phényl-1(pipérazinyl-1)-3-indazoles-1H, procédé et intermédiares pour leur préparation, et leur utilisations comme médicaments |
US4999356A (en) * | 1987-08-07 | 1991-03-12 | Hoechst-Roussel Pharmaceuticals, Inc. | 1-phenyl-3-(1-piperazinyl)-1H-indazoles |
CA1335289C (fr) * | 1987-10-26 | 1995-04-18 | Fujio Antoku | Derives piperidinylbenzisoxazole, leur production et leur utilisation pharmaceutique |
JPH01199967A (ja) * | 1987-10-26 | 1989-08-11 | Sumitomo Pharmaceut Co Ltd | 新規なイミド誘導体 |
US4880930A (en) | 1987-11-30 | 1989-11-14 | New James S | Psychotropic acyclic amide derivatives |
US5001130A (en) * | 1988-02-18 | 1991-03-19 | Bristol-Myers Company | Psychotropic heterobicycloalkylpiperazine derivatives |
US4780466A (en) * | 1988-03-17 | 1988-10-25 | Hoechst-Roussel Pharmaceuticals, Inc. | Arylpiperazinylalkoxy derivatives of cyclic imides |
NZ230045A (en) * | 1988-08-05 | 1990-11-27 | Janssen Pharmaceutica Nv | 3-piperazinylbenzazole derivatives and pharmaceutical compositions |
IL90879A0 (en) | 1988-09-02 | 1990-02-09 | Janssen Pharmaceutica Nv | 3-piperidinyl-indazole derivatives,their preparation and antihypertensive compositions containing them |
FR2641278B1 (fr) * | 1989-01-05 | 1991-03-22 | Lipha | Piperidines, procedes de preparation et medicaments les contenant |
NZ233503A (en) | 1989-05-15 | 1991-06-25 | Janssen Pharmaceutica Nv | Substituted (thio)morpholinyl and piperazinyl alkylphenol ethers |
NZ233525A (en) * | 1989-05-15 | 1991-09-25 | Janssen Pharmaceutica Nv | Piperidinyl, pyrrolidinyl and piperazinyl alkylphenol ethers and pharmaceutical compositions |
DE69021645T2 (de) * | 1989-05-19 | 1996-02-22 | Hoechst-Roussel Pharmaceuticals Inc., Somerville, N.J. | N-(aryloxyalkyl)heteroarylpiperidine und -heteroarylpiperazine, Verfahren zu ihrer Herstellung und ihre Verwendung als Medikamente. |
US5364866A (en) | 1989-05-19 | 1994-11-15 | Hoechst-Roussel Pharmaceuticals, Inc. | Heteroarylpiperidines, pyrrolidines and piperazines and their use as antipsychotics and analetics |
US4954503A (en) * | 1989-09-11 | 1990-09-04 | Hoechst-Roussel Pharmaceuticals, Inc. | 3-(1-substituted-4-piperazinyl)-1H-indazoles |
US4968792A (en) * | 1989-09-25 | 1990-11-06 | American Home Products Corporation | Psychotropic benzisothiazole derivatives |
JP2800953B2 (ja) * | 1990-07-06 | 1998-09-21 | 住友製薬株式会社 | 新規なイミド誘導体 |
WO1993009012A1 (fr) | 1991-10-31 | 1993-05-13 | Allied-Signal, Inc. | Systeme de frein electohydraulique |
GB9202915D0 (en) * | 1992-02-12 | 1992-03-25 | Wellcome Found | Chemical compounds |
GB9302622D0 (en) | 1993-02-10 | 1993-03-24 | Wellcome Found | Heteroaromatic compounds |
-
1992
- 1992-10-30 US US07/969,383 patent/US5364866A/en not_active Ceased
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- 1992-11-04 EP EP01102643A patent/EP1110954A1/fr not_active Withdrawn
- 1992-11-04 DK DK99111017T patent/DK0959076T3/da active
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- 1992-11-04 EP EP99111314A patent/EP0959075B1/fr not_active Expired - Lifetime
- 1992-11-04 RU RU94028105/04A patent/RU2127731C1/ru active
- 1992-11-04 WO PCT/US1992/009276 patent/WO1993009102A1/fr active IP Right Grant
- 1992-11-04 DK DK99111314.3T patent/DK0959075T3/da active
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- 1992-11-05 EP EP00115401A patent/EP1052255A1/fr not_active Withdrawn
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- 1992-11-05 EP EP99111016A patent/EP0957102A1/fr not_active Withdrawn
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1994
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