ES2298425T7 - Derivados de fenil-piperazina como inhibidores de la captación de serotonina - Google Patents
Derivados de fenil-piperazina como inhibidores de la captación de serotonina Download PDFInfo
- Publication number
- ES2298425T7 ES2298425T7 ES02800051T ES02800051T ES2298425T7 ES 2298425 T7 ES2298425 T7 ES 2298425T7 ES 02800051 T ES02800051 T ES 02800051T ES 02800051 T ES02800051 T ES 02800051T ES 2298425 T7 ES2298425 T7 ES 2298425T7
- Authority
- ES
- Spain
- Prior art keywords
- alk
- phenyl
- compounds
- compound
- pharmaceutically acceptable
- 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.)
- Active
Links
- 239000003772 serotonin uptake inhibitor Substances 0.000 title description 9
- YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical class C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 title description 2
- 150000003839 salts Chemical class 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 12
- 208000019901 Anxiety disease Diseases 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- YQNWZWMKLDQSAC-UHFFFAOYSA-N vortioxetine Chemical compound CC1=CC(C)=CC=C1SC1=CC=CC=C1N1CCNCC1 YQNWZWMKLDQSAC-UHFFFAOYSA-N 0.000 claims description 5
- 208000019022 Mood disease Diseases 0.000 claims description 3
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 208000019906 panic disease Diseases 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 description 53
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- 239000000243 solution Substances 0.000 description 26
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 25
- 238000000034 method Methods 0.000 description 25
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical class ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 22
- -1 but not limited to Chemical group 0.000 description 20
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
- 238000000105 evaporative light scattering detection Methods 0.000 description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
- 239000011347 resin Substances 0.000 description 16
- 229920005989 resin Polymers 0.000 description 16
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 14
- 239000000203 mixture Substances 0.000 description 13
- 239000002904 solvent Substances 0.000 description 11
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 10
- 239000007858 starting material Substances 0.000 description 10
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 9
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 8
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 8
- 239000004793 Polystyrene Substances 0.000 description 7
- 229920002223 polystyrene Polymers 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 230000001430 anti-depressive effect Effects 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 4
- 238000010511 deprotection reaction Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 125000002950 monocyclic group Chemical group 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 230000000697 serotonin reuptake Effects 0.000 description 4
- 229940126570 serotonin reuptake inhibitor Drugs 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 3
- PWKNBLFSJAVFAB-UHFFFAOYSA-N 1-fluoro-2-nitrobenzene Chemical class [O-][N+](=O)C1=CC=CC=C1F PWKNBLFSJAVFAB-UHFFFAOYSA-N 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000003875 Wang resin Substances 0.000 description 3
- NERFNHBZJXXFGY-UHFFFAOYSA-N [4-[(4-methylphenyl)methoxy]phenyl]methanol Chemical compound C1=CC(C)=CC=C1COC1=CC=C(CO)C=C1 NERFNHBZJXXFGY-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 239000000935 antidepressant agent Substances 0.000 description 3
- 229940005513 antidepressants Drugs 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 150000004985 diamines Chemical class 0.000 description 3
- 150000001989 diazonium salts Chemical class 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- CYJAWBVQRMVFEO-UHFFFAOYSA-N piperazine-2,6-dione Chemical class O=C1CNCC(=O)N1 CYJAWBVQRMVFEO-UHFFFAOYSA-N 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
- BMKKDXDTIILJLH-UHFFFAOYSA-N (1-bromocyclohexa-2,4-dien-1-yl)sulfanylbenzene Chemical class C=1C=CC=CC=1SC1(Br)CC=CC=C1 BMKKDXDTIILJLH-UHFFFAOYSA-N 0.000 description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 2
- OFCNTYBPPAQCRE-UHFFFAOYSA-N 3-(2-aminoethyl)-3h-indol-5-ol Chemical compound C1=C(O)C=C2C(CCN)C=NC2=C1 OFCNTYBPPAQCRE-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 208000020401 Depressive disease Diseases 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- 230000003416 augmentation Effects 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 229910000085 borane Inorganic materials 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- 239000012954 diazonium Substances 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 238000004255 ion exchange chromatography Methods 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 238000001690 micro-dialysis Methods 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 238000001050 pharmacotherapy Methods 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 2
- 239000003727 serotonin 1A antagonist Substances 0.000 description 2
- 239000004000 serotonin 1B antagonist Substances 0.000 description 2
- 230000013275 serotonin uptake Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 210000003568 synaptosome Anatomy 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- ONRFBYRISLAHAI-UHFFFAOYSA-N (1-bromocyclohexa-2,4-dien-1-yl)oxybenzene Chemical class C=1C=CC=CC=1OC1(Br)CC=CC=C1 ONRFBYRISLAHAI-UHFFFAOYSA-N 0.000 description 1
- 125000006553 (C3-C8) cycloalkenyl group Chemical group 0.000 description 1
- WSEQXVZVJXJVFP-HXUWFJFHSA-N (R)-citalopram Chemical compound C1([C@@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-HXUWFJFHSA-N 0.000 description 1
- UGUHFDPGDQDVGX-UHFFFAOYSA-N 1,2,3-thiadiazole Chemical compound C1=CSN=N1 UGUHFDPGDQDVGX-UHFFFAOYSA-N 0.000 description 1
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- XVDNGXHEWBPHCS-UHFFFAOYSA-N 1,2,4-dioxazine Chemical compound O1OC=NC=C1 XVDNGXHEWBPHCS-UHFFFAOYSA-N 0.000 description 1
- STOZZANTYUATHO-UHFFFAOYSA-N 1,2,4-dithiazine Chemical compound S1SC=NC=C1 STOZZANTYUATHO-UHFFFAOYSA-N 0.000 description 1
- GPYCKQNJWXEDII-UHFFFAOYSA-N 1,2,4-oxathiazine Chemical compound O1SC=NC=C1 GPYCKQNJWXEDII-UHFFFAOYSA-N 0.000 description 1
- FYADHXFMURLYQI-UHFFFAOYSA-N 1,2,4-triazine Chemical compound C1=CN=NC=N1 FYADHXFMURLYQI-UHFFFAOYSA-N 0.000 description 1
- WTPCCFHCHCMJIT-UHFFFAOYSA-N 1,2,5-oxathiazine Chemical compound O1SC=CN=C1 WTPCCFHCHCMJIT-UHFFFAOYSA-N 0.000 description 1
- FFJBRYXQVYFDEQ-UHFFFAOYSA-N 1,3,2-dioxazole Chemical compound N1OC=CO1 FFJBRYXQVYFDEQ-UHFFFAOYSA-N 0.000 description 1
- PJDDGXBBYQKCBV-UHFFFAOYSA-N 1,3,2-dithiazole Chemical compound N1SC=CS1 PJDDGXBBYQKCBV-UHFFFAOYSA-N 0.000 description 1
- BPLPLJIEXQORJJ-UHFFFAOYSA-N 1,3,2-oxathiazole Chemical compound N1OC=CS1 BPLPLJIEXQORJJ-UHFFFAOYSA-N 0.000 description 1
- UKOMUVPFRFPHDS-UHFFFAOYSA-N 1,4,2-dioxazine Chemical compound O1C=CON=C1 UKOMUVPFRFPHDS-UHFFFAOYSA-N 0.000 description 1
- DDGWEFMIIOIMEF-UHFFFAOYSA-N 1,4,2-dithiazine Chemical compound S1C=CSN=C1 DDGWEFMIIOIMEF-UHFFFAOYSA-N 0.000 description 1
- FMYSHKHSQFXYRS-UHFFFAOYSA-N 1,4,2-oxathiazine Chemical compound O1C=CSC=N1 FMYSHKHSQFXYRS-UHFFFAOYSA-N 0.000 description 1
- UCXSZDUQAFCNSQ-UHFFFAOYSA-N 1,4,3-oxathiazine Chemical compound O1C=CSN=C1 UCXSZDUQAFCNSQ-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- KVGZZAHHUNAVKZ-UHFFFAOYSA-N 1,4-Dioxin Chemical compound O1C=COC=C1 KVGZZAHHUNAVKZ-UHFFFAOYSA-N 0.000 description 1
- AKAIWNDBVZJOAJ-UHFFFAOYSA-N 1,4-dithiine Chemical compound S1C=CSC=C1 AKAIWNDBVZJOAJ-UHFFFAOYSA-N 0.000 description 1
- CPRVXMQHLPTWLY-UHFFFAOYSA-N 1,4-oxathiine Chemical compound O1C=CSC=C1 CPRVXMQHLPTWLY-UHFFFAOYSA-N 0.000 description 1
- IAPUIIIXYHXCRV-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)sulfanylphenyl]-3,5-dimethylpiperazine Chemical compound C1C(C)NC(C)CN1C1=CC=CC=C1SC1=CC=C(Cl)C=C1 IAPUIIIXYHXCRV-UHFFFAOYSA-N 0.000 description 1
- KQZFLCYOCXDFBQ-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)sulfanylphenyl]-3-methylpiperazine Chemical compound C1CNC(C)CN1C1=CC=CC=C1SC1=CC=C(Cl)C=C1 KQZFLCYOCXDFBQ-UHFFFAOYSA-N 0.000 description 1
- REFSEMZDFSMMGK-UHFFFAOYSA-N 1-[2-[2-(trifluoromethyl)phenyl]sulfanylphenyl]piperazine Chemical compound FC(F)(F)C1=CC=CC=C1SC1=CC=CC=C1N1CCNCC1 REFSEMZDFSMMGK-UHFFFAOYSA-N 0.000 description 1
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 1
- CYUPFFKTTJMWLE-UHFFFAOYSA-N 1-bromo-2-(4-methylphenyl)sulfanylbenzene Chemical compound C1=CC(C)=CC=C1SC1=CC=CC=C1Br CYUPFFKTTJMWLE-UHFFFAOYSA-N 0.000 description 1
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 1
- 239000005631 2,4-Dichlorophenoxyacetic acid Substances 0.000 description 1
- DEFBBVSVIMXNCP-UHFFFAOYSA-N 2-(3-methylpiperazin-1-yl)aniline Chemical compound C1CNC(C)CN1C1=CC=CC=C1N DEFBBVSVIMXNCP-UHFFFAOYSA-N 0.000 description 1
- KGFFMVMQCXIUOX-UHFFFAOYSA-N 2-(4-methylphenyl)sulfanylaniline Chemical compound C1=CC(C)=CC=C1SC1=CC=CC=C1N KGFFMVMQCXIUOX-UHFFFAOYSA-N 0.000 description 1
- XVGQHRKNXSUPEF-UHFFFAOYSA-N 2-(trifluoromethyl)benzenethiol Chemical compound FC(F)(F)C1=CC=CC=C1S XVGQHRKNXSUPEF-UHFFFAOYSA-N 0.000 description 1
- UEKVCYGLSNMFPQ-UHFFFAOYSA-N 2-[butoxycarbonyl(carboxymethyl)amino]acetic acid Chemical compound CCCCOC(=O)N(CC(O)=O)CC(O)=O UEKVCYGLSNMFPQ-UHFFFAOYSA-N 0.000 description 1
- JOMNTHCQHJPVAZ-UHFFFAOYSA-N 2-methylpiperazine Chemical compound CC1CNCCN1 JOMNTHCQHJPVAZ-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- HPYLZSUEFFQHRS-UHFFFAOYSA-N 2h-1,2,4-oxadiazine Chemical compound N1OC=CN=C1 HPYLZSUEFFQHRS-UHFFFAOYSA-N 0.000 description 1
- YROIEQHEBPTQKR-UHFFFAOYSA-N 2h-1,2,4-thiadiazine Chemical compound N1SC=CN=C1 YROIEQHEBPTQKR-UHFFFAOYSA-N 0.000 description 1
- DGTQLIRLDYOSQF-UHFFFAOYSA-N 2h-1,2,5-oxadiazine Chemical compound N1OC=NC=C1 DGTQLIRLDYOSQF-UHFFFAOYSA-N 0.000 description 1
- OHDJISGEMQIVIJ-UHFFFAOYSA-N 2h-1,2,5-thiadiazine Chemical compound N1SC=NC=C1 OHDJISGEMQIVIJ-UHFFFAOYSA-N 0.000 description 1
- DOESEUHFGCHXFW-UHFFFAOYSA-N 2h-1,2,6-thiadiazine Chemical compound N1SN=CC=C1 DOESEUHFGCHXFW-UHFFFAOYSA-N 0.000 description 1
- HCNVXDPRTRLNFX-UHFFFAOYSA-N 2h-1,3,4-oxadiazine Chemical compound C1OC=CN=N1 HCNVXDPRTRLNFX-UHFFFAOYSA-N 0.000 description 1
- KLVQAIJZDCCJRZ-UHFFFAOYSA-N 2h-1,3,4-thiadiazine Chemical compound C1SC=CN=N1 KLVQAIJZDCCJRZ-UHFFFAOYSA-N 0.000 description 1
- KGWNRZLPXLBMPS-UHFFFAOYSA-N 2h-1,3-oxazine Chemical compound C1OC=CC=N1 KGWNRZLPXLBMPS-UHFFFAOYSA-N 0.000 description 1
- NTYABNDBNKVWOO-UHFFFAOYSA-N 2h-1,3-thiazine Chemical compound C1SC=CC=N1 NTYABNDBNKVWOO-UHFFFAOYSA-N 0.000 description 1
- YHWMFDLNZGIJSD-UHFFFAOYSA-N 2h-1,4-oxazine Chemical compound C1OC=CN=C1 YHWMFDLNZGIJSD-UHFFFAOYSA-N 0.000 description 1
- ZAISDHPZTZIFQF-UHFFFAOYSA-N 2h-1,4-thiazine Chemical compound C1SC=CN=C1 ZAISDHPZTZIFQF-UHFFFAOYSA-N 0.000 description 1
- VRJMDLLQRTTXLD-UHFFFAOYSA-N 2h-1,5,2-dioxazine Chemical compound C1ONC=CO1 VRJMDLLQRTTXLD-UHFFFAOYSA-N 0.000 description 1
- WIKVRBTVPSOQHJ-UHFFFAOYSA-N 2h-1,5,2-dithiazine Chemical compound C1SNC=CS1 WIKVRBTVPSOQHJ-UHFFFAOYSA-N 0.000 description 1
- QMEQBOSUJUOXMX-UHFFFAOYSA-N 2h-oxadiazine Chemical compound N1OC=CC=N1 QMEQBOSUJUOXMX-UHFFFAOYSA-N 0.000 description 1
- BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 description 1
- QBYTXRKLVZHFND-UHFFFAOYSA-N 2h-thiadiazine Chemical compound N1SC=CC=N1 QBYTXRKLVZHFND-UHFFFAOYSA-N 0.000 description 1
- AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical compound N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 description 1
- QMDFJHAAWUGVKQ-UHFFFAOYSA-N 2h-thiopyran Chemical compound C1SC=CC=C1 QMDFJHAAWUGVKQ-UHFFFAOYSA-N 0.000 description 1
- UNTNRNUQVKDIPV-UHFFFAOYSA-N 3h-dithiazole Chemical compound N1SSC=C1 UNTNRNUQVKDIPV-UHFFFAOYSA-N 0.000 description 1
- KWIVRAVCZJXOQC-UHFFFAOYSA-N 3h-oxathiazole Chemical compound N1SOC=C1 KWIVRAVCZJXOQC-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- VYNPRPGSCKKCQV-UHFFFAOYSA-N 4-chlorothiophene Chemical compound ClC1=[C]SC=C1 VYNPRPGSCKKCQV-UHFFFAOYSA-N 0.000 description 1
- SDEBYHVDMCQKNZ-UHFFFAOYSA-N 4-methoxy-6-piperazin-1-ylpyrimidine;hydrochloride Chemical compound Cl.C1=NC(OC)=CC(N2CCNCC2)=N1 SDEBYHVDMCQKNZ-UHFFFAOYSA-N 0.000 description 1
- IBDPSLIRLQQZIQ-UHFFFAOYSA-N 4h-1,3,2-dioxazine Chemical compound C1ONOC=C1 IBDPSLIRLQQZIQ-UHFFFAOYSA-N 0.000 description 1
- NVUUCLSJAYQJKJ-UHFFFAOYSA-N 4h-1,3,2-dithiazine Chemical compound C1SNSC=C1 NVUUCLSJAYQJKJ-UHFFFAOYSA-N 0.000 description 1
- UCZQXJKDCHCTAI-UHFFFAOYSA-N 4h-1,3-dioxine Chemical compound C1OCC=CO1 UCZQXJKDCHCTAI-UHFFFAOYSA-N 0.000 description 1
- FSCYPXBTOHREPQ-UHFFFAOYSA-N 4h-1,3-dithiine Chemical compound C1SCC=CS1 FSCYPXBTOHREPQ-UHFFFAOYSA-N 0.000 description 1
- SKTFQHRVFFOHTQ-UHFFFAOYSA-N 8-bromo-1,3-dimethyl-7h-purine-2,6-dione Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC(Br)=N2 SKTFQHRVFFOHTQ-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 102000007527 Autoreceptors Human genes 0.000 description 1
- 108010071131 Autoreceptors Proteins 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 238000003650 Calcium Assay Kit Methods 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 201000001880 Sexual dysfunction Diseases 0.000 description 1
- 206010041250 Social phobia Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical compound IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 description 1
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 1
- PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 125000005129 aryl carbonyl group Chemical group 0.000 description 1
- 150000001503 aryl iodides Chemical class 0.000 description 1
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical class C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 150000003841 chloride salts Chemical class 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N cinnamic acid group Chemical class C(C=CC1=CC=CC=C1)(=O)O WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 229960001653 citalopram Drugs 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 150000000117 diazepanes Chemical class 0.000 description 1
- 238000006193 diazotization reaction Methods 0.000 description 1
- PPSZHCXTGRHULJ-UHFFFAOYSA-N dioxazine Chemical compound O1ON=CC=C1 PPSZHCXTGRHULJ-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- QFWWKJJQZCWKPL-UHFFFAOYSA-N dithiazine Chemical compound S1SN=CC=C1 QFWWKJJQZCWKPL-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000012039 electrophile Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 238000005558 fluorometry Methods 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- NBZBKCUXIYYUSX-UHFFFAOYSA-N iminodiacetic acid Chemical compound OC(=O)CNCC(O)=O NBZBKCUXIYYUSX-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 150000002505 iron Chemical class 0.000 description 1
- 150000004698 iron complex Chemical class 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
- 229910052808 lithium carbonate Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000000336 melanocortin receptor agonist Substances 0.000 description 1
- 229910001510 metal chloride Inorganic materials 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000004050 mood stabilizer Substances 0.000 description 1
- 229940127237 mood stabilizer Drugs 0.000 description 1
- 125000005322 morpholin-1-yl group Chemical group 0.000 description 1
- 230000008450 motivation Effects 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- QXLNAYIFEMXTDZ-UHFFFAOYSA-N n-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-4-[2-methyl-4-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl]benzamide Chemical compound C1=C(N2CCN(C)CC2)C(OC)=CC=C1NC(=O)C(C=C1)=CC=C1C(C(=C1)C)=CC=C1C1=NN=C(C)O1 QXLNAYIFEMXTDZ-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- AZHVQJLDOFKHPZ-UHFFFAOYSA-N oxathiazine Chemical compound O1SN=CC=C1 AZHVQJLDOFKHPZ-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
- 239000004031 partial agonist Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 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 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 231100000872 sexual dysfunction Toxicity 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- COHLCPVRWDSZSC-UHFFFAOYSA-N tert-butyl 4-[2-(4-methylphenyl)sulfanylphenyl]-3,5-dioxopiperazine-1-carboxylate Chemical compound C1=CC(C)=CC=C1SC1=CC=CC=C1N1C(=O)CN(C(=O)OC(C)(C)C)CC1=O COHLCPVRWDSZSC-UHFFFAOYSA-N 0.000 description 1
- JOXNAPLQMZNQGR-UHFFFAOYSA-N tert-butyl 4-hydroxy-4-[2-(4-methylphenyl)sulfanylphenyl]piperidine-1-carboxylate Chemical compound C1=CC(C)=CC=C1SC1=CC=CC=C1C1(O)CCN(C(=O)OC(C)(C)C)CC1 JOXNAPLQMZNQGR-UHFFFAOYSA-N 0.000 description 1
- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- 229940035722 triiodothyronine Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/145—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- 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
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/70—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/08—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/02—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements
- C07D295/027—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring
- C07D295/033—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring with the ring nitrogen atoms directly attached to carbocyclic rings
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic 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 |
|---|---|---|---|
| DKPA200101466 | 2001-10-04 | ||
| DK200101466 | 2001-10-04 | ||
| PCT/DK2002/000659 WO2003029232A1 (en) | 2001-10-04 | 2002-10-02 | Phenyl-piperazine derivatives as serotonin reuptake inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| ES2298425T3 ES2298425T3 (es) | 2008-05-16 |
| ES2298425T7 true ES2298425T7 (es) | 2022-06-27 |
Family
ID=8160750
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES06016609T Expired - Lifetime ES2328725T3 (es) | 2001-10-04 | 2002-10-02 | Derivados de fenilpiridina como inhibidores de la reabsorcion de serotonina. |
| ES02800051T Active ES2298425T7 (es) | 2001-10-04 | 2002-10-02 | Derivados de fenil-piperazina como inhibidores de la captación de serotonina |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES06016609T Expired - Lifetime ES2328725T3 (es) | 2001-10-04 | 2002-10-02 | Derivados de fenilpiridina como inhibidores de la reabsorcion de serotonina. |
Country Status (38)
Families Citing this family (104)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| UA81749C2 (uk) | 2001-10-04 | 2008-02-11 | Х. Луннбек А/С | Фенілпіперазинові похідні як інгібітори зворотного захоплення серотоніну |
| GB0305575D0 (en) * | 2003-03-11 | 2003-04-16 | Glaxo Group Ltd | Novel compounds |
| MXPA05009592A (es) * | 2003-04-04 | 2005-10-18 | Lundbeck & Co As H | Derivados de 4-(2-fenilsulfanil-fenil)-piperidina como inhibidores de recaptacion de serotonina. |
| BRPI0408647A (pt) * | 2003-04-04 | 2006-03-07 | Lundbeck & Co As H | composto, composição farmacêutica, uso de um composto, e, método para o tratamento de um distúrbio afetivo |
| EP1635828B1 (en) * | 2003-04-04 | 2008-04-23 | H. Lundbeck A/S | 4-(2-phenyloxyphenyl)-piperidine or -1,2,3,6-tetrahydropyridine derivatives as serotonin reuptake inhibitors |
| UA81300C2 (en) * | 2003-04-04 | 2007-12-25 | Lundbeck & Co As H | Derivates of 4-(2-fenilsulfanilfenil)-1,2,3,6-tetrahydropiridin as retarding agents of serotonin recapture |
| KR20050119682A (ko) * | 2003-04-04 | 2005-12-21 | 하. 룬트벡 아크티에 셀스카브 | 세로토닌 재흡수 억제제로서 4-(2-페닐옥시페닐)-피페리딘또는 -1,2,3,6-테트라히드로피리딘 유도체 |
| WO2005061455A1 (en) | 2003-12-23 | 2005-07-07 | H. Lundbeck A/S | 2-(1h-indolylsulfanyl)-benzyl amine derivatives as ssri |
| AR052308A1 (es) | 2004-07-16 | 2007-03-14 | Lundbeck & Co As H | Derivados de 2-(1h-indolilsulfanil)-arilamina y una composicion farmaceutica que contiene al compuesto |
| US7923444B2 (en) | 2005-02-10 | 2011-04-12 | Neurosearch A/S | Alkyl substituted homopiperazine derivatives and their use as monoamine neurotransmitter re-uptake inhibitors |
| AR054394A1 (es) * | 2005-06-17 | 2007-06-20 | Lundbeck & Co As H | Derivados de 2- (1h-indolilsulfanil)-aril amina |
| AR054393A1 (es) * | 2005-06-17 | 2007-06-20 | Lundbeck & Co As H | Derivados de benzo(b)furano y benzo(b)tiofeno, composiciones farmaceuticas que los contienen y su uso en la fabricacion de un medicamento para el tratamiento de enfermedades mediadas por la inhibicion de la reabsorcion de neurotransmisores de amina biogenicos. |
| US7629473B2 (en) | 2005-06-17 | 2009-12-08 | H. Lundbeck A/S | 2-(1H-indolylsulfanyl)-aryl amine derivatives |
| JP2007106746A (ja) * | 2005-09-13 | 2007-04-26 | Tosoh Corp | 新規アリールホモピペラジン類、またはその塩と製造方法 |
| KR101445514B1 (ko) * | 2006-06-16 | 2014-09-29 | 하. 룬트벡 아크티에 셀스카브 | 인지기능 장애의 치료를 위한, 세로토닌 재흡수, 5-ht3 및 5-ht1a 활성이 조합된 화합물로서의 1-[2-(2,4-디메틸페닐술파닐)-페닐]피페라진 |
| JP7179035B2 (ja) * | 2006-06-16 | 2022-11-28 | ハー・ルンドベック・アクチエゼルスカベット | 認識機能障害（ｃｏｇｎｉｔｉｖｅ ｉｍｐａｉｒｍｅｎｔ）を治療するための、組み合わされたセロトニン再取り込み、５－ＨＴ３および５－ＨＴ１Ａ活性を有する化合物としての１－［２－（２，４－ジメチルフェニルスルファニル）－フェニル］ピペラジン |
| WO2007144006A1 (en) * | 2006-06-16 | 2007-12-21 | H. Lundbeck A/S | Crystalline forms of 4- [2- (4-methylphenylsulfanyl) -phenyl] piperidine with combined serotonin and norepinephrine reuptake inhibition for the treatment of neuropathic pain |
| RS51687B (en) * | 2006-06-16 | 2011-10-31 | H. Lundbeck A/S. | CRYSTAL FORMS 4- [2-4- (4-METHYLPHENYLSULPHANYL) PHENYL] PIPERIDINE WITH COMBINED INHIBITION OF SEROTONIN AND NOREPINEPHRINE REASPORPTION FOR TREATMENT OF NEUROPATIC PAIN |
| UA95801C2 (ru) * | 2006-06-16 | 2011-09-12 | Х. Луннбек А/С | Кристаллические формы 4-[2-(4-метилфенилсульфанил)-фенил]пиперидина с комбинированным ингибированием обратного захвата серотонина и норэпинефрина для лечения невропатической боли |
| TW200848411A (en) | 2007-03-20 | 2008-12-16 | Lundbeck & Co As H | Novel therapeutic uses of 1-[2-(2, 4-dimethylphenylsulfanyl)phenyl]-piperazine |
| TWI432194B (zh) * | 2007-03-20 | 2014-04-01 | Lundbeck & Co As H | ４-〔２-（４-甲基苯硫基）苯基〕哌啶之新穎治療用途 |
| TWI405588B (zh) | 2007-03-20 | 2013-08-21 | Lundbeck & Co As H | ４-〔２-（４-甲苯基硫基）-苯基〕哌啶之鹽類的液體調配物 |
| JP5764327B2 (ja) * | 2007-06-15 | 2015-08-19 | ハー・ルンドベック・アクチエゼルスカベット | 過敏性腸症候群（ｉｂｓ）を処置するための４−［２−（４−メチルフェニルスルファニル）フェニル］ピペリジン |
| TW200932233A (en) * | 2007-11-13 | 2009-08-01 | Lundbeck & Co As H | Therapeutic uses of compounds having combined SERT, 5-HT3 and 5-HT1a activity |
| AU2014200364B2 (en) * | 2007-11-13 | 2015-09-17 | H. Lundbeck A/S | Therapeutic uses of compounds having combined SERT, 5-HT3 and 5-HT1A activity |
| TW200938194A (en) * | 2007-12-14 | 2009-09-16 | Lundbeck & Co As H | Therapeutic uses of compounds having affinity to the serotonin transporter, serotonin receptors and noradrenalin transporter |
| TW200932225A (en) * | 2007-12-14 | 2009-08-01 | Lundbeck & Co As H | 4-[2,3-difluoro-6-(2-fluoro-4-methyl-phenylsulfanyl)-phenyl]-piperidine |
| WO2009081259A1 (en) * | 2007-12-21 | 2009-07-02 | Pfizer Inc. | Phenoxy-pyridyl derivatives |
| UA98698C2 (en) * | 2008-03-03 | 2012-06-11 | Х. Луннбек А/С | Phenylsulfanylphenyl-piperidines and process for the preparation thereof |
| EP2358674B1 (en) | 2008-11-14 | 2013-01-02 | Theravance, Inc. | Process for preparing 4-[2-(2-fluorophenoxymethyl)phenyl]piperidine compounds |
| TW201033181A (en) | 2009-02-17 | 2010-09-16 | Lundbeck & Co As H | Purification of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine |
| RS53539B1 (en) | 2009-04-24 | 2015-02-27 | H. Lundbeck A/S | LIQUID FORMULATIONS OF SALES 1- [2- (2,4-DIMETHYLPHENYLSULPHANYL) PHENYL] PIPERAZINE |
| NZ598083A (en) * | 2009-08-24 | 2013-08-30 | Lundbeck & Co As H | New compositions of 1-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]piperazine |
| CA2779108C (en) * | 2009-10-30 | 2018-01-02 | Janssen Pharmaceutica Nv | 4-substituted-2-phenoxy-phenylamine delta opioid receptor modulators |
| WO2011085291A1 (en) | 2010-01-11 | 2011-07-14 | Theravance, Inc. | 1 - (2 - phenoxymethylphenyl) piperazine compounds as serotonin and norepinephrine reuptake inhibitors |
| US8530663B2 (en) * | 2010-03-22 | 2013-09-10 | Theravance, Inc. | 1-(2-phenoxymethylheteroaryl)piperidine and piperazine compounds |
| KR20130060220A (ko) | 2010-04-30 | 2013-06-07 | 다케다 야쿠힌 고교 가부시키가이샤 | 장용성 정제 |
| MY162392A (en) * | 2010-04-30 | 2017-06-15 | Takeda Pharmaceuticals Co | Enteric tablet |
| EP2407467A1 (de) | 2010-07-14 | 2012-01-18 | Sandoz Ag | Kristalline Verbindung von 1-[4-(2-azepan-1-yl-ethoxy)-benzyl]-2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol und Milchsäure |
| TW201212918A (en) | 2010-08-23 | 2012-04-01 | Lundbeck & Co As H | Therapeutic uses of 1-[2-(2,4-dimethyl-phenylsulfanyl)phenyl]piperazine |
| ES2601213T3 (es) | 2011-06-20 | 2017-02-14 | H. Lundbeck A/S | 1-piperazino-3-fenil-indanos deuterados para el tratamiento de la esquizofrenia |
| RU2622082C2 (ru) | 2011-11-14 | 2017-06-09 | Нестек С.А. | Анализы и способы выбора режима лечения пациента с депрессией |
| RU2608307C2 (ru) * | 2012-01-03 | 2017-01-17 | Х.Лундбек А/С | Способ получения 1-[2-(2,4-диметилфенилсульфанил)фенил]пиперазина |
| CN104797566B (zh) | 2012-09-19 | 2017-07-07 | 桑多斯股份公司 | 沃替西汀氢溴酸盐的新结晶形式 |
| MY171802A (en) | 2012-12-13 | 2019-10-30 | H Lundbeck As | Compositions comprising vortioxetine and donepezil |
| LT2958903T (lt) * | 2013-02-22 | 2017-08-25 | H. Lundbeck A/S | Vortioksetino gamybos būdas |
| US9493409B2 (en) | 2013-04-04 | 2016-11-15 | Lek Pharmaceuticals D.D. | Process for the synthesis of 1-(2-((2,4-dimethylphenyl)thio)phenyl)piperazine |
| CN104109135B (zh) * | 2013-04-22 | 2018-10-26 | 江苏豪森药业集团有限公司 | 1-[2-(2,4-二甲基苯基硫烷基)-苯基]哌嗪的制备方法 |
| IN2013MU03121A (OSRAM) | 2013-09-30 | 2015-07-17 | Cadila Healthcare Ltd | |
| EP2878596A1 (en) * | 2013-11-29 | 2015-06-03 | LEK Pharmaceuticals d.d. | Synthesis of vortioxetine via (2-(piperazine-1-yl)phenyl)lithium intermediates |
| CN104710345B (zh) * | 2013-12-17 | 2017-09-05 | 江苏恩华药业股份有限公司 | 用于制备4‑（2‑（4‑甲基苯基硫基））苯基哌啶的化合物、其制备方法及应用 |
| EP3082815B1 (en) | 2013-12-20 | 2018-10-03 | H. Lundbeck A/S | Use of an opioid receptor antagonist with kappa-activity and vortioxetine for treatment of depressive disorder with melancholic features |
| EP2894154A1 (en) * | 2014-01-14 | 2015-07-15 | LEK Pharmaceuticals d.d. | Synthesis of vortioxetine via (2-(piperazine-1-yl)phenyl)aniline intermediates |
| CN103788019B (zh) * | 2014-01-22 | 2015-10-07 | 苏州明锐医药科技有限公司 | 沃替西汀的制备方法 |
| CN106103418A (zh) | 2014-01-31 | 2016-11-09 | 埃吉斯药物私人有限公司 | 沃替西汀盐的制备方法 |
| EP2930171A1 (en) | 2014-04-07 | 2015-10-14 | LEK Pharmaceuticals d.d. | Synthesis of vortioxetine via (2,4-dimethylphenyl)(2-iodophenyl)sulfane intermediate |
| CN104059030B (zh) | 2014-05-30 | 2016-05-04 | 镇江圣安医药有限公司 | [(苯硫烷基)-苯基]哌嗪的衍生物及其药物组合物和用途 |
| FR3023320B1 (fr) * | 2014-07-03 | 2017-03-10 | Ifp Energies Now | Systeme et procede de stockage et de recuperation d'energie par gaz comprime avec stockage de la chaleur au moyen d'un echangeur radial |
| CZ2014471A3 (cs) | 2014-07-08 | 2016-01-20 | Zentiva, K.S. | Způsob přípravy vortioxetinu |
| US9687484B2 (en) | 2014-07-18 | 2017-06-27 | Dipharma Francis S.R.L. | Crystalline forms of an antidepressant compound |
| CN104146953A (zh) * | 2014-07-24 | 2014-11-19 | 李雪梅 | 一种氢溴酸沃替西汀注射液 |
| CN104292183B (zh) * | 2014-09-29 | 2016-01-06 | 杨献美 | 一种抗抑郁药物沃替西汀的制备方法 |
| WO2016079751A2 (en) | 2014-11-17 | 2016-05-26 | Megafine Pharma (P) Ltd. | A process for preparation of vortioxetine and polymorphs thereof |
| ES2634496T3 (es) | 2014-11-21 | 2017-09-28 | Dipharma Francis S.R.L. | Proceso para la preparación de un antidepresivo y los intermedios del mismo |
| CN104447622B (zh) * | 2014-11-28 | 2017-01-04 | 郑州大明药物科技有限公司 | 氢溴酸沃替西汀β晶型的制备方法 |
| CN104586756A (zh) * | 2015-01-05 | 2015-05-06 | 万特制药(海南)有限公司 | 一种含沃替西汀的口服溶液及其制备方法 |
| CZ201531A3 (cs) | 2015-01-21 | 2016-08-03 | Zentiva, K.S. | Polymerem stabilizované amorfní formy vortioxetinu |
| CN104610195B (zh) * | 2015-01-30 | 2017-06-27 | 上虞京新药业有限公司 | 沃替西汀的天冬氨酸盐或其水合物及其制备方法和用途 |
| WO2016125191A2 (en) | 2015-02-04 | 2016-08-11 | Mylan Laboratories Limited | Processes for the preparation of vortioxetine hydrobromide |
| WO2016125190A2 (en) | 2015-02-04 | 2016-08-11 | Mylan Laboratories Limited | Novel crystalline forms of vortioxetine, premixes, and processes for the preparation thereof |
| EP3262031A1 (en) | 2015-02-25 | 2018-01-03 | Lupin Limited | Process for the preparation of vortioxetine |
| WO2016151328A1 (en) | 2015-03-26 | 2016-09-29 | Cipla Limited | Method for making serotonin reuptake inhibitors |
| CN104829557B (zh) * | 2015-04-23 | 2017-06-27 | 山东百诺医药股份有限公司 | 一种新化合物1‑[2‑（2,4‑二甲基苯基硫基）苯基]‑2‑氧哌嗪及其制备方法和在沃替西汀合成中的应用 |
| JO3456B1 (ar) | 2015-05-13 | 2020-07-05 | H Lundbeck As | فيروتيوكسيتين بيروجلوتامات |
| MX386470B (es) | 2015-07-17 | 2025-03-18 | Pasteur Institut | Agente estimulador del receptor 5-hidroxi triptamina 1b para usarse como un promotor de la autorrenovación y/o diferenciación de células satélite. |
| EP3337789A1 (en) * | 2015-08-19 | 2018-06-27 | Amneal Pharmaceuticals Company GmbH | Process for preparation of vortioxetine hydrobromide |
| WO2017063771A1 (en) * | 2015-10-14 | 2017-04-20 | Institut Pasteur | 5-hydroxytryptamine 1b receptor-stimulating agent for the treatment of myocardial infarction |
| CN105461635B (zh) * | 2015-11-18 | 2018-06-08 | 乳源瑶族自治县大众药品贸易有限公司 | 苯基哌嗪衍生物及其使用方法和用途 |
| CN105348204B (zh) * | 2015-11-18 | 2018-09-14 | 乳源瑶族自治县大众药品贸易有限公司 | 1-杂环基-2-(杂芳基硫基)苯衍生物及其使用方法和用途 |
| US11013830B2 (en) | 2015-11-20 | 2021-05-25 | Institut Pasteur | 5-hydroxytryptamine 1B receptor-stimulating agent for enhancing in vivo engraftment potential |
| WO2017162536A1 (en) | 2016-03-21 | 2017-09-28 | H. Lundbeck A/S | Vortioxetine prodrugs |
| RU2018144248A (ru) * | 2016-07-01 | 2020-08-03 | Х. Лундбекк А/С | Схемы дозирования вортиоксетина для быстрого появления антидепрессивного эффекта |
| EP3484462B1 (en) | 2016-07-15 | 2022-12-14 | Institut Pasteur | 5-hydroxytryptamine 1b receptor-stimulating agent for skin and/or hair repair |
| KR20190032418A (ko) * | 2016-07-22 | 2019-03-27 | 지앙수 인화뤄캉 파마슈티컬 리서치 앤드 디벨롭먼트 컴퍼니 리미티드 | 보티옥세틴 유사체와 용도 및 이의 제조 |
| US20190224192A1 (en) | 2016-08-29 | 2019-07-25 | Cipla Limited | Stable Pharmaceutical Composition of Vortioxetine Hydrobromide |
| CN106349132B (zh) * | 2016-08-30 | 2018-02-02 | 重庆植恩药业有限公司 | 沃替西汀中间体杂质及其制备方法和用途 |
| US10519121B2 (en) | 2016-12-30 | 2019-12-31 | Apicore Us Llc | Process and novel polymorphic form of vortioxetine and its pharmaceutically acceptable salts |
| CN108409728B (zh) * | 2017-02-09 | 2020-11-24 | 广东东阳光药业有限公司 | 苯基八氢-1H-吡啶并[1,2-a]吡嗪衍生物及其用途 |
| CN108409729B (zh) * | 2017-02-09 | 2020-11-24 | 广东东阳光药业有限公司 | 苯基八氢-1H-吡啶并[1,2-a]吡嗪衍生物及其用途 |
| US10428033B2 (en) | 2017-02-15 | 2019-10-01 | Piramal Enterprises Limited | Process for the preparation of vortioxetine and salts thereof |
| WO2018150344A1 (en) | 2017-02-17 | 2018-08-23 | Unichem Laboratories Ltd | Bioequivalent pharmaceutical composition of vortioxetine hydrobromide |
| EP3585388A4 (en) | 2017-02-23 | 2020-08-12 | Unichem Laboratories Ltd | IMPROVED PROCESS FOR PREPARATION AND PURIFICATION OF VORTIOXETINE BROMHYDRATE |
| MA49056A (fr) * | 2017-04-25 | 2020-03-04 | H Lundbeck As | Procédé de fabrication de la forme alpha de vortioxétine hbr |
| EP3412661A1 (en) | 2017-06-08 | 2018-12-12 | Enantia, S.L. | Cocrystals of vortioxetine hydrobromide and resorcinol |
| KR102026337B1 (ko) | 2017-07-07 | 2019-09-27 | 영진약품 주식회사 | 1-[2-(2,4-디메틸페닐설파닐)페닐]피페라진의 신규염 및 이의 제조방법 |
| CN107915685A (zh) * | 2017-12-11 | 2018-04-17 | 重庆植恩药业有限公司 | 一种氢溴酸沃替西汀中间体的制备方法 |
| CN108017595A (zh) * | 2017-12-20 | 2018-05-11 | 安徽源久源科技有限公司 | 一种1-[2-(2,5-二甲基苯硫基)苯基]哌嗪的制备方法 |
| WO2019242889A1 (en) | 2018-06-20 | 2019-12-26 | Vio Ag Pharmaceuticals S.A. | A one-pot organo-pseudocatalytic c-h activation approach for the preparation of vortioxetine and vortioxetine intermediate |
| CN108863986B (zh) * | 2018-08-06 | 2020-01-21 | 广东东阳光药业有限公司 | 二氟甲基取代的苯基哌嗪衍生物及其用途 |
| CN108727393B (zh) * | 2018-08-06 | 2019-10-29 | 广东东阳光药业有限公司 | 苯基二氮杂双环衍生物及其用途 |
| AU2021246973A1 (en) | 2020-04-03 | 2022-11-03 | H. Lundbeck A/S | 1-(2-(2,4-dimethylphenylsulfanyl)-phenyl)piperazine for prevention or treatment of emotional blunting |
| US12281088B2 (en) | 2020-09-10 | 2025-04-22 | Suzhou Fude Zhaofeng Biochemical Technology Co., Ltd | Process for the synthesis of vortioxetine |
| GB2622880A (en) | 2022-09-30 | 2024-04-03 | Alkaloid Ad Skopje | Palatable orodispersible formulation of vortioxetine |
| WO2025132869A1 (en) | 2023-12-21 | 2025-06-26 | H. Lundbeck A/S | Method for the preparation of vortioxetine pharmaceutical compositions with low amounts of nitrosamine impurities |
Family Cites Families (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CS151751B1 (OSRAM) | 1971-04-13 | 1973-11-19 | ||
| CS151752B1 (OSRAM) | 1971-04-13 | 1973-11-19 | ||
| CS151753B1 (OSRAM) | 1971-04-13 | 1973-11-19 | ||
| CS151755B1 (OSRAM) | 1971-04-13 | 1973-11-19 | ||
| YU163075A (en) | 1975-07-21 | 1982-05-31 | Science Union & Cie | Process for preparing new phenoxy derivatives |
| US4241071A (en) | 1977-01-27 | 1980-12-23 | American Hoechst Corporation | Antidepressant (α-phenyl-2-tolyl)azacycloalkanes |
| US4198419A (en) | 1979-01-10 | 1980-04-15 | American Hoechst Corporation | Phenylthiophenylpiperidines |
| US4198417A (en) | 1979-01-10 | 1980-04-15 | American Hoechst Corporation | Phenoxyphenylpiperidines |
| ES2004809A6 (es) | 1987-07-29 | 1989-02-01 | Ferrer Int | Procedimiento de obtencion de nuevas 1-(2-(fenilmetil)fenil)piperazinas |
| GB9126311D0 (en) | 1991-12-11 | 1992-02-12 | Wellcome Found | Substituted diphenylsulfides |
| WO1996022977A1 (fr) | 1995-01-23 | 1996-08-01 | Suntory Limited | Ameliorant ou remede contre des symptomes provoques par des maladies ischemiques et composes utiles a cet effet |
| CZ293595A3 (cs) | 1995-11-09 | 1999-12-15 | Farmak A. S. | Deriváty N,N-dimethyl-2-(arylthio)benzylaminu, jejich soli, způsoby jejich přípravy a jejich použití v léčivých přípravcích |
| FR2757160B1 (fr) * | 1996-12-13 | 1999-03-12 | Sanofi Sa | 1-phenylalkyl-1,2,3,6-tetrahydropyridines |
| US6297239B1 (en) | 1997-10-08 | 2001-10-02 | Merck & Co., Inc. | Inhibitors of prenyl-protein transferase |
| ES2230209T3 (es) * | 1997-10-31 | 2005-05-01 | Daiichi Suntory Pharma Co., Ltd. | Procedimiento para preparar n-((4-fenil)metilfenil)piperazinas. |
| AU774054B2 (en) | 1999-04-02 | 2004-06-17 | Icos Corporation | Inhibitors of LFA-1 binding to ICAMs and uses thereof |
| WO2001010842A2 (en) | 1999-08-04 | 2001-02-15 | Millennium Pharmaceuticals, Inc. | Melanocortin-4 receptor binding compounds and methods of use thereof |
| CA2384599A1 (en) * | 1999-09-14 | 2001-03-22 | Pharmacopeia, Inc. | Article comprising a multi-channel dispensing head |
| ATE261959T1 (de) * | 1999-12-30 | 2004-04-15 | Lundbeck & Co As H | Substituierte phenyl-piperazin-derivate, deren herstellung und verwendung |
| EP1246819A1 (en) * | 1999-12-30 | 2002-10-09 | H. Lundbeck A/S | A method for the preparation of substituted benzene derivatives |
| US6813639B2 (en) | 2000-01-26 | 2004-11-02 | Viaclix, Inc. | Method for establishing channel-based internet access network |
| DE10033548C2 (de) | 2000-07-11 | 2002-05-16 | Wolfgang Papenbrock | Verfahren zur Vorschau von Internetseiten |
| EP1370558B1 (en) | 2001-01-23 | 2005-08-24 | Eli Lilly And Company | Piperazine- and piperidine-derivatives as melanocortin receptor agonists |
| EP1363890A4 (en) | 2001-02-07 | 2009-06-10 | Ore Pharmaceuticals Inc | MELANOCORTIN-4-RECEPTOR BINDING COMPOUNDS AND METHOD FOR THEIR APPLICATION |
| UA81749C2 (uk) | 2001-10-04 | 2008-02-11 | Х. Луннбек А/С | Фенілпіперазинові похідні як інгібітори зворотного захоплення серотоніну |
| EP1458689B1 (en) * | 2001-12-20 | 2007-04-11 | H. Lundbeck A/S | Aryloxyphenyl and arylsulfanylphenyl derivatives |
| AR043633A1 (es) | 2003-03-20 | 2005-08-03 | Schering Corp | Ligandos de receptores de canabinoides |
| MXPA05009592A (es) * | 2003-04-04 | 2005-10-18 | Lundbeck & Co As H | Derivados de 4-(2-fenilsulfanil-fenil)-piperidina como inhibidores de recaptacion de serotonina. |
| WO2005000309A2 (en) | 2003-06-27 | 2005-01-06 | Ionix Pharmaceuticals Limited | Chemical compounds |
| KR101445514B1 (ko) * | 2006-06-16 | 2014-09-29 | 하. 룬트벡 아크티에 셀스카브 | 인지기능 장애의 치료를 위한, 세로토닌 재흡수, 5-ht3 및 5-ht1a 활성이 조합된 화합물로서의 1-[2-(2,4-디메틸페닐술파닐)-페닐]피페라진 |
-
2002
- 2002-02-10 UA UA2004032271A patent/UA81749C2/uk unknown
- 2002-09-30 AR ARP020103689A patent/AR036659A1/es active IP Right Grant
- 2002-10-02 HR HR20040220A patent/HRP20040220A2/hr not_active Application Discontinuation
- 2002-10-02 PT PT06016609T patent/PT1749818E/pt unknown
- 2002-10-02 DK DK06016609T patent/DK1749818T3/da active
- 2002-10-02 AT AT06016609T patent/ATE441631T1/de active
- 2002-10-02 EA EA200400498A patent/EA007537B3/ru active Protection Beyond IP Right Term
- 2002-10-02 HU HU0402313A patent/HU228956B1/hu active Protection Beyond IP Right Term
- 2002-10-02 IL IL16065502A patent/IL160655A0/xx active Protection Beyond IP Right Term
- 2002-10-02 SI SI200230678T patent/SI1436271T1/sl unknown
- 2002-10-02 CN CNB028190254A patent/CN1319958C/zh not_active Expired - Lifetime
- 2002-10-02 BR BRPI0212733A patent/BRPI0212733B8/pt active IP Right Grant
- 2002-10-02 ES ES06016609T patent/ES2328725T3/es not_active Expired - Lifetime
- 2002-10-02 EA EA200601269A patent/EA011096B1/ru not_active IP Right Cessation
- 2002-10-02 RS RS20120158A patent/RS52865B/en unknown
- 2002-10-02 AU AU2002333220A patent/AU2002333220C1/en active Active
- 2002-10-02 KR KR1020077022025A patent/KR100842702B1/ko not_active Expired - Lifetime
- 2002-10-02 HU HU1300028A patent/HU230189B1/hu unknown
- 2002-10-02 EP EP02800051.1A patent/EP1436271B3/en not_active Expired - Lifetime
- 2002-10-02 PT PT02800051T patent/PT1436271E/pt unknown
- 2002-10-02 NZ NZ531556A patent/NZ531556A/en not_active IP Right Cessation
- 2002-10-02 CA CA2462110A patent/CA2462110C/en not_active Expired - Lifetime
- 2002-10-02 UA UAA200612495A patent/UA93857C2/uk unknown
- 2002-10-02 ME MEP-2008-65A patent/ME00039B/me unknown
- 2002-10-02 BR BR122012009534D patent/BR122012009534C8/pt not_active IP Right Cessation
- 2002-10-02 AT AT02800051T patent/ATE386730T1/de active
- 2002-10-02 DK DK02800051.1T patent/DK1436271T6/da active
- 2002-10-02 EG EG2002101084A patent/EG25095A/xx active
- 2002-10-02 WO PCT/DK2002/000659 patent/WO2003029232A1/en active IP Right Grant
- 2002-10-02 DE DE60233608T patent/DE60233608D1/de not_active Expired - Lifetime
- 2002-10-02 RS YU27704A patent/RS52326B/en unknown
- 2002-10-02 KR KR1020067022562A patent/KR100783346B1/ko not_active Expired - Lifetime
- 2002-10-02 KR KR1020047004897A patent/KR100770194B1/ko not_active Expired - Lifetime
- 2002-10-02 US US10/488,280 patent/US7144884B2/en active Active
- 2002-10-02 PL PL392184A patent/PL210551B1/pl unknown
- 2002-10-02 BR BR122012023120A patent/BR122012023120B8/pt active IP Right Grant
- 2002-10-02 PL PL368442A patent/PL209253B1/pl unknown
- 2002-10-02 MX MXPA04002959A patent/MXPA04002959A/es active IP Right Grant
- 2002-10-02 ES ES02800051T patent/ES2298425T7/es active Active
- 2002-10-02 EP EP06016609A patent/EP1749818B1/en not_active Expired - Lifetime
- 2002-10-02 JP JP2003532482A patent/JP3896116B2/ja not_active Expired - Lifetime
- 2002-10-02 DE DE60225162.1T patent/DE60225162T3/de not_active Expired - Lifetime
- 2002-10-03 MY MYPI20023705A patent/MY140950A/en unknown
-
2004
- 2004-02-26 ZA ZA2004/01583A patent/ZA200401583B/en unknown
- 2004-02-26 IS IS7164A patent/IS2578B/is unknown
- 2004-04-21 NO NO20041628A patent/NO326443B1/no active IP Right Maintenance
- 2004-04-30 CO CO04039958A patent/CO5580746A2/es not_active Application Discontinuation
-
2005
- 2005-12-06 US US11/296,836 patent/US7148238B2/en not_active Expired - Lifetime
- 2005-12-06 US US11/296,835 patent/US7138407B2/en not_active Expired - Lifetime
-
2006
- 2006-09-14 AU AU2006215994A patent/AU2006215994B2/en not_active Ceased
- 2006-10-03 JP JP2006271758A patent/JP3955613B2/ja not_active Expired - Lifetime
- 2006-10-03 JP JP2006271762A patent/JP3955614B2/ja not_active Expired - Lifetime
- 2006-10-19 US US11/551,188 patent/US7683053B2/en not_active Expired - Fee Related
-
2008
- 2008-04-18 CY CY20081100436T patent/CY1107924T1/el unknown
- 2008-05-06 AR ARP080101915A patent/AR066460A2/es active IP Right Grant
- 2008-08-06 NO NO20083446A patent/NO332355B1/no not_active IP Right Cessation
-
2009
- 2009-03-10 IS IS8806A patent/IS2732B/is unknown
- 2009-10-14 CY CY20091101068T patent/CY1110064T1/el unknown
-
2010
- 2010-02-04 US US12/700,521 patent/US8110567B2/en not_active Expired - Fee Related
-
2012
- 2012-02-06 US US13/367,065 patent/US8476279B2/en not_active Expired - Fee Related
-
2013
- 2013-06-26 US US13/927,678 patent/US9090575B2/en not_active Expired - Fee Related
-
2014
- 2014-03-07 NL NL300652C patent/NL300652I1/nl unknown
- 2014-03-12 LU LU92397C patent/LU92397I2/fr unknown
- 2014-03-12 HU HUS1400012C patent/HUS1400012I1/hu unknown
- 2014-03-13 LT LTPA2014013C patent/LTC1436271I2/lt unknown
- 2014-04-16 FR FR14C0033C patent/FR14C0033I2/fr active Active
- 2014-05-13 NO NO2014011C patent/NO2014011I2/no not_active IP Right Cessation
- 2014-06-03 BE BE2014C036C patent/BE2014C036I2/nl unknown
- 2014-06-11 CY CY2014022C patent/CY2014022I2/el unknown
-
2015
- 2015-06-19 US US14/744,197 patent/US9708280B2/en not_active Expired - Fee Related
-
2017
- 2017-06-15 US US15/624,417 patent/US10844029B2/en not_active Expired - Fee Related
-
2020
- 2020-10-22 US US17/078,055 patent/US20210276966A1/en not_active Abandoned
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2298425T7 (es) | Derivados de fenil-piperazina como inhibidores de la captación de serotonina | |
| AU2002333220A1 (en) | Phenyl-piperazine derivatives as serotonin reuptake inhibitors |