ES2432102T3 - Compuestos con actividad combinada en SERT, 5-HT3 y 5-HT1A - Google Patents
Compuestos con actividad combinada en SERT, 5-HT3 y 5-HT1A Download PDFInfo
- Publication number
- ES2432102T3 ES2432102T3 ES11193235T ES11193235T ES2432102T3 ES 2432102 T3 ES2432102 T3 ES 2432102T3 ES 11193235 T ES11193235 T ES 11193235T ES 11193235 T ES11193235 T ES 11193235T ES 2432102 T3 ES2432102 T3 ES 2432102T3
- Authority
- ES
- Spain
- Prior art keywords
- compound
- mixture
- piperazine
- toluene
- phenyl
- 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
- 150000001875 compounds Chemical class 0.000 title claims abstract description 164
- 230000000694 effects Effects 0.000 title description 38
- 102100022738 5-hydroxytryptamine receptor 1A Human genes 0.000 title description 24
- 101710138638 5-hydroxytryptamine receptor 1A Proteins 0.000 title description 20
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 38
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims abstract description 23
- 239000002904 solvent Substances 0.000 claims abstract description 19
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 11
- 239000003446 ligand Substances 0.000 claims abstract description 11
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims abstract description 11
- 239000001257 hydrogen Substances 0.000 claims abstract description 10
- 239000003054 catalyst Substances 0.000 claims abstract description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 5
- 125000006239 protecting group Chemical group 0.000 claims abstract description 5
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 4
- 150000002367 halogens Chemical class 0.000 claims abstract description 4
- 229910052751 metal Inorganic materials 0.000 claims abstract description 4
- 239000002184 metal Substances 0.000 claims abstract description 4
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims abstract 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 141
- 239000000203 mixture Substances 0.000 claims description 75
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 65
- 239000000243 solution Substances 0.000 claims description 53
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 46
- 238000000034 method Methods 0.000 claims description 42
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 41
- YQNWZWMKLDQSAC-UHFFFAOYSA-N vortioxetine Chemical compound CC1=CC(C)=CC=C1SC1=CC=CC=C1N1CCNCC1 YQNWZWMKLDQSAC-UHFFFAOYSA-N 0.000 claims description 41
- 150000003839 salts Chemical class 0.000 claims description 39
- 230000008569 process Effects 0.000 claims description 28
- 238000010992 reflux Methods 0.000 claims description 28
- 238000006243 chemical reaction Methods 0.000 claims description 24
- 239000000047 product Substances 0.000 claims description 18
- -1 2,4-Dimethyl-phenylsulfanyl Chemical group 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 14
- OIRHKGBNGGSCGS-UHFFFAOYSA-N 1-bromo-2-iodobenzene Chemical compound BrC1=CC=CC=C1I OIRHKGBNGGSCGS-UHFFFAOYSA-N 0.000 claims description 12
- AMNLXDDJGGTIPL-UHFFFAOYSA-N 2,4-dimethylbenzenethiol Chemical compound CC1=CC=C(S)C(C)=C1 AMNLXDDJGGTIPL-UHFFFAOYSA-N 0.000 claims description 10
- 239000007864 aqueous solution Substances 0.000 claims description 10
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 claims description 9
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 9
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 claims description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
- VNGRUFUIHGGOOM-UHFFFAOYSA-N vortioxetine hydrobromide Chemical compound Br.CC1=CC(C)=CC=C1SC1=CC=CC=C1N1CCNCC1 VNGRUFUIHGGOOM-UHFFFAOYSA-N 0.000 claims description 8
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims description 7
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- WQONPSCCEXUXTQ-UHFFFAOYSA-N 1,2-dibromobenzene Chemical compound BrC1=CC=CC=C1Br WQONPSCCEXUXTQ-UHFFFAOYSA-N 0.000 claims description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 4
- 125000003944 tolyl group Chemical group 0.000 claims description 3
- ZEMZPXWZVTUONV-UHFFFAOYSA-N 2-(2-dicyclohexylphosphanylphenyl)-n,n-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 ZEMZPXWZVTUONV-UHFFFAOYSA-N 0.000 claims description 2
- PHLPNEHPCYZBNZ-UHFFFAOYSA-N 2-(2-ditert-butylphosphanylphenyl)-n,n-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1C1=CC=CC=C1P(C(C)(C)C)C(C)(C)C PHLPNEHPCYZBNZ-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 2
- CNXMDTWQWLGCPE-UHFFFAOYSA-N ditert-butyl-(2-phenylphenyl)phosphane Chemical compound CC(C)(C)P(C(C)(C)C)C1=CC=CC=C1C1=CC=CC=C1 CNXMDTWQWLGCPE-UHFFFAOYSA-N 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 150000002500 ions Chemical class 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 claims description 2
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical group C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 claims 6
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 claims 2
- AFUDYMRCVMXUBD-UHFFFAOYSA-N 5-bromo-5-iodocyclohexa-1,3-diene Chemical compound BrC1(I)CC=CC=C1 AFUDYMRCVMXUBD-UHFFFAOYSA-N 0.000 claims 1
- 239000000010 aprotic solvent Substances 0.000 claims 1
- 239000007795 chemical reaction product Substances 0.000 claims 1
- 239000012973 diazabicyclooctane Substances 0.000 claims 1
- LCSNDSFWVKMJCT-UHFFFAOYSA-N dicyclohexyl-(2-phenylphenyl)phosphane Chemical compound C1CCCCC1P(C=1C(=CC=CC=1)C=1C=CC=CC=1)C1CCCCC1 LCSNDSFWVKMJCT-UHFFFAOYSA-N 0.000 claims 1
- LUNZAASWPICGPB-UHFFFAOYSA-N dicyclohexyl-[2-(2,4,6-tripropylphenyl)phenyl]phosphane Chemical compound CCCC1=CC(CCC)=CC(CCC)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 LUNZAASWPICGPB-UHFFFAOYSA-N 0.000 claims 1
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- ZGNPLWZYVAFUNZ-UHFFFAOYSA-N tert-butylphosphane Chemical compound CC(C)(C)P ZGNPLWZYVAFUNZ-UHFFFAOYSA-N 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 65
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 64
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 54
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 48
- 238000011282 treatment Methods 0.000 description 42
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 36
- 239000008187 granular material Substances 0.000 description 33
- 208000010877 cognitive disease Diseases 0.000 description 32
- 238000001914 filtration Methods 0.000 description 32
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 208000028698 Cognitive impairment Diseases 0.000 description 29
- 239000007787 solid Substances 0.000 description 29
- 208000002193 Pain Diseases 0.000 description 24
- 235000019439 ethyl acetate Nutrition 0.000 description 24
- 235000019359 magnesium stearate Nutrition 0.000 description 24
- 238000012360 testing method Methods 0.000 description 24
- 239000012458 free base Substances 0.000 description 23
- 241000700159 Rattus Species 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- 229920002261 Corn starch Polymers 0.000 description 20
- 238000005481 NMR spectroscopy Methods 0.000 description 20
- 230000006399 behavior Effects 0.000 description 20
- 239000008120 corn starch Substances 0.000 description 20
- 239000000725 suspension Substances 0.000 description 20
- 241001465754 Metazoa Species 0.000 description 19
- 229910052757 nitrogen Inorganic materials 0.000 description 19
- 229960005141 piperazine Drugs 0.000 description 18
- 230000015572 biosynthetic process Effects 0.000 description 17
- 238000012512 characterization method Methods 0.000 description 17
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 17
- 238000000634 powder X-ray diffraction Methods 0.000 description 17
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 16
- 229920001531 copovidone Polymers 0.000 description 16
- 201000010099 disease Diseases 0.000 description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 16
- 239000008108 microcrystalline cellulose Substances 0.000 description 16
- 229940016286 microcrystalline cellulose Drugs 0.000 description 16
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 16
- 238000001556 precipitation Methods 0.000 description 16
- 239000011541 reaction mixture Substances 0.000 description 16
- 238000002844 melting Methods 0.000 description 15
- 230000008018 melting Effects 0.000 description 15
- 239000000843 powder Substances 0.000 description 15
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 15
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 14
- 238000004128 high performance liquid chromatography Methods 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 13
- 229960004373 acetylcholine Drugs 0.000 description 13
- 230000015654 memory Effects 0.000 description 13
- 239000003921 oil Substances 0.000 description 13
- 235000019198 oils Nutrition 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 238000001035 drying Methods 0.000 description 12
- 238000000921 elemental analysis Methods 0.000 description 12
- 238000002474 experimental method Methods 0.000 description 12
- 238000010438 heat treatment Methods 0.000 description 12
- 230000014759 maintenance of location Effects 0.000 description 12
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 11
- 230000003750 conditioning effect Effects 0.000 description 11
- 230000007170 pathology Effects 0.000 description 11
- 239000012071 phase Substances 0.000 description 11
- 239000000523 sample Substances 0.000 description 11
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 11
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 11
- 238000012549 training Methods 0.000 description 11
- 102000035037 5-HT3 receptors Human genes 0.000 description 10
- 108091005477 5-HT3 receptors Proteins 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 230000004044 response Effects 0.000 description 9
- 238000005406 washing Methods 0.000 description 9
- 208000019901 Anxiety disease Diseases 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 8
- 229920003083 Kollidon® VA64 Polymers 0.000 description 8
- 229920002472 Starch Polymers 0.000 description 8
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 8
- 229940032147 starch Drugs 0.000 description 8
- 239000008107 starch Substances 0.000 description 8
- 235000019698 starch Nutrition 0.000 description 8
- FEWJPZIEWOKRBE-XIXRPRMCSA-N Mesotartaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-XIXRPRMCSA-N 0.000 description 7
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 7
- 239000012267 brine Substances 0.000 description 7
- 230000001149 cognitive effect Effects 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 230000001050 lubricating effect Effects 0.000 description 7
- 230000036961 partial effect Effects 0.000 description 7
- 229920003109 sodium starch glycolate Polymers 0.000 description 7
- 239000008109 sodium starch glycolate Substances 0.000 description 7
- 229940079832 sodium starch glycolate Drugs 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- 208000024827 Alzheimer disease Diseases 0.000 description 6
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 6
- 229930195725 Mannitol Natural products 0.000 description 6
- 239000007832 Na2SO4 Substances 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 230000008485 antagonism Effects 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 6
- 210000004556 brain Anatomy 0.000 description 6
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 6
- 230000006735 deficit Effects 0.000 description 6
- 235000019700 dicalcium phosphate Nutrition 0.000 description 6
- 230000000977 initiatory effect Effects 0.000 description 6
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 6
- 239000000594 mannitol Substances 0.000 description 6
- 235000010355 mannitol Nutrition 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 229920002785 Croscarmellose sodium Polymers 0.000 description 5
- 229920003110 Primojel Polymers 0.000 description 5
- 206010041250 Social phobia Diseases 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 5
- 230000001270 agonistic effect Effects 0.000 description 5
- 230000003920 cognitive function Effects 0.000 description 5
- 229960001681 croscarmellose sodium Drugs 0.000 description 5
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 5
- 238000010511 deprotection reaction Methods 0.000 description 5
- 239000001530 fumaric acid Substances 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 229960001021 lactose monohydrate Drugs 0.000 description 5
- 208000019906 panic disease Diseases 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 230000000697 serotonin reuptake Effects 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 239000012453 solvate Substances 0.000 description 5
- 238000012453 sprague-dawley rat model Methods 0.000 description 5
- 239000000454 talc Substances 0.000 description 5
- 235000012222 talc Nutrition 0.000 description 5
- 229910052623 talc Inorganic materials 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- FGTISJUBEGSYIP-UHFFFAOYSA-N 1-(2-bromophenyl)sulfanyl-2,4-dimethylbenzene Chemical compound CC1=CC(C)=CC=C1SC1=CC=CC=C1Br FGTISJUBEGSYIP-UHFFFAOYSA-N 0.000 description 4
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 4
- 208000020401 Depressive disease Diseases 0.000 description 4
- 101000822895 Homo sapiens 5-hydroxytryptamine receptor 1A Proteins 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 208000028552 Treatment-Resistant Depressive disease Diseases 0.000 description 4
- 206010047700 Vomiting Diseases 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 239000002671 adjuvant Substances 0.000 description 4
- 230000036506 anxiety Effects 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 239000012467 final product Substances 0.000 description 4
- 239000008241 heterogeneous mixture Substances 0.000 description 4
- 210000001320 hippocampus Anatomy 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 208000002551 irritable bowel syndrome Diseases 0.000 description 4
- 208000024714 major depressive disease Diseases 0.000 description 4
- 238000001690 micro-dialysis Methods 0.000 description 4
- 239000010502 orange oil Substances 0.000 description 4
- 210000002442 prefrontal cortex Anatomy 0.000 description 4
- 201000000980 schizophrenia Diseases 0.000 description 4
- 229940126570 serotonin reuptake inhibitor Drugs 0.000 description 4
- 239000003772 serotonin uptake inhibitor Substances 0.000 description 4
- 230000007958 sleep Effects 0.000 description 4
- 229940023144 sodium glycolate Drugs 0.000 description 4
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 4
- 201000009032 substance abuse Diseases 0.000 description 4
- 208000011117 substance-related disease Diseases 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 4
- 238000002411 thermogravimetry Methods 0.000 description 4
- JEJAMASKDTUEBZ-UHFFFAOYSA-N tris(1,1,3-tribromo-2,2-dimethylpropyl) phosphate Chemical compound BrCC(C)(C)C(Br)(Br)OP(=O)(OC(Br)(Br)C(C)(C)CBr)OC(Br)(Br)C(C)(C)CBr JEJAMASKDTUEBZ-UHFFFAOYSA-N 0.000 description 4
- 210000005111 ventral hippocampus Anatomy 0.000 description 4
- IGKYREHZJIHPML-UNTBIKODSA-N 2-[4-[[(2r)-3,4-dihydro-2h-chromen-2-yl]methylamino]butyl]-1,1-dioxo-1,2-benzothiazol-3-one;hydron;chloride Chemical compound Cl.O=S1(=O)C2=CC=CC=C2C(=O)N1CCCCNC[C@@H]1OC2=CC=CC=C2CC1 IGKYREHZJIHPML-UNTBIKODSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 3
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 3
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 208000000094 Chronic Pain Diseases 0.000 description 3
- 208000030814 Eating disease Diseases 0.000 description 3
- 208000019454 Feeding and Eating disease Diseases 0.000 description 3
- 229910002651 NO3 Inorganic materials 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 3
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 102000019208 Serotonin Plasma Membrane Transport Proteins Human genes 0.000 description 3
- 108010012996 Serotonin Plasma Membrane Transport Proteins Proteins 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000008484 agonism Effects 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 239000000935 antidepressant agent Substances 0.000 description 3
- 229940005513 antidepressants Drugs 0.000 description 3
- 230000000949 anxiolytic effect Effects 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 230000000747 cardiac effect Effects 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 3
- 229960001231 choline Drugs 0.000 description 3
- 230000001713 cholinergic effect Effects 0.000 description 3
- 230000019771 cognition Effects 0.000 description 3
- 230000007278 cognition impairment Effects 0.000 description 3
- 238000007596 consolidation process Methods 0.000 description 3
- 235000019788 craving Nutrition 0.000 description 3
- 230000003001 depressive effect Effects 0.000 description 3
- 238000004807 desolvation Methods 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 235000014632 disordered eating Nutrition 0.000 description 3
- 229940011871 estrogen Drugs 0.000 description 3
- 239000000262 estrogen Substances 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 239000011261 inert gas Substances 0.000 description 3
- 230000013016 learning Effects 0.000 description 3
- 230000007595 memory recall Effects 0.000 description 3
- 208000004296 neuralgia Diseases 0.000 description 3
- 239000004031 partial agonist Substances 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 229940076279 serotonin Drugs 0.000 description 3
- 239000003369 serotonin 5-HT3 receptor antagonist Substances 0.000 description 3
- 201000002859 sleep apnea Diseases 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 231100000736 substance abuse Toxicity 0.000 description 3
- ODELUUDFRPTTTC-UHFFFAOYSA-N tert-butyl 4-[2-(2,4-dimethylphenyl)sulfanylphenyl]piperazine-1-carboxylate Chemical compound CC1=CC(C)=CC=C1SC1=CC=CC=C1N1CCN(C(=O)OC(C)(C)C)CC1 ODELUUDFRPTTTC-UHFFFAOYSA-N 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- 150000007944 thiolates Chemical class 0.000 description 3
- 230000008448 thought Effects 0.000 description 3
- 238000005550 wet granulation Methods 0.000 description 3
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 2
- FELGMEQIXOGIFQ-CYBMUJFWSA-N (3r)-9-methyl-3-[(2-methylimidazol-1-yl)methyl]-2,3-dihydro-1h-carbazol-4-one Chemical compound CC1=NC=CN1C[C@@H]1C(=O)C(C=2C(=CC=CC=2)N2C)=C2CC1 FELGMEQIXOGIFQ-CYBMUJFWSA-N 0.000 description 2
- CQSVBPFCYHGUJN-WLHGVMLRSA-N (e)-but-2-enedioic acid;1-[2-(2,4-dimethylphenyl)sulfanylphenyl]piperazine Chemical compound OC(=O)\C=C\C(O)=O.CC1=CC(C)=CC=C1SC1=CC=CC=C1N1CCNCC1 CQSVBPFCYHGUJN-WLHGVMLRSA-N 0.000 description 2
- IVSZLXZYQVIEFR-UHFFFAOYSA-N 1,3-Dimethylbenzene Natural products CC1=CC=CC(C)=C1 IVSZLXZYQVIEFR-UHFFFAOYSA-N 0.000 description 2
- PZASAAIJIFDWSB-CKPDSHCKSA-N 8-[(1S)-1-[8-(trifluoromethyl)-7-[4-(trifluoromethyl)cyclohexyl]oxynaphthalen-2-yl]ethyl]-8-azabicyclo[3.2.1]octane-3-carboxylic acid Chemical compound FC(F)(F)C=1C2=CC([C@@H](N3C4CCC3CC(C4)C(O)=O)C)=CC=C2C=CC=1OC1CCC(C(F)(F)F)CC1 PZASAAIJIFDWSB-CKPDSHCKSA-N 0.000 description 2
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- 208000008035 Back Pain Diseases 0.000 description 2
- 241001631457 Cannula Species 0.000 description 2
- 206010008479 Chest Pain Diseases 0.000 description 2
- 108010000659 Choline oxidase Proteins 0.000 description 2
- 208000023890 Complex Regional Pain Syndromes Diseases 0.000 description 2
- 229920000858 Cyclodextrin Polymers 0.000 description 2
- FEWJPZIEWOKRBE-LWMBPPNESA-L D-tartrate(2-) Chemical compound [O-]C(=O)[C@@H](O)[C@H](O)C([O-])=O FEWJPZIEWOKRBE-LWMBPPNESA-L 0.000 description 2
- 206010012289 Dementia Diseases 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 206010052804 Drug tolerance Diseases 0.000 description 2
- 208000001640 Fibromyalgia Diseases 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 208000033830 Hot Flashes Diseases 0.000 description 2
- 206010060800 Hot flush Diseases 0.000 description 2
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- 235000019502 Orange oil Nutrition 0.000 description 2
- 206010033664 Panic attack Diseases 0.000 description 2
- 206010034912 Phobia Diseases 0.000 description 2
- 206010036376 Postherpetic Neuralgia Diseases 0.000 description 2
- 201000009916 Postpartum depression Diseases 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 208000028017 Psychotic disease Diseases 0.000 description 2
- 201000001880 Sexual dysfunction Diseases 0.000 description 2
- 206010066218 Stress Urinary Incontinence Diseases 0.000 description 2
- 230000003109 amnesic effect Effects 0.000 description 2
- 230000000202 analgesic effect Effects 0.000 description 2
- 230000003042 antagnostic effect Effects 0.000 description 2
- 230000000338 anxiogenic effect Effects 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 238000011952 auditory verbal learning test Methods 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 208000003295 carpal tunnel syndrome Diseases 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 210000003710 cerebral cortex Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 239000010779 crude oil Substances 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 239000000385 dialysis solution Substances 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 238000011990 functional testing Methods 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
- 230000026781 habituation Effects 0.000 description 2
- 239000012456 homogeneous solution Substances 0.000 description 2
- AUONNNVJUCSETH-UHFFFAOYSA-N icosanoyl icosanoate Chemical compound CCCCCCCCCCCCCCCCCCCC(=O)OC(=O)CCCCCCCCCCCCCCCCCCC AUONNNVJUCSETH-UHFFFAOYSA-N 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 229910052738 indium Inorganic materials 0.000 description 2
- 239000013067 intermediate product Substances 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 238000005461 lubrication Methods 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 229960001785 mirtazapine Drugs 0.000 description 2
- RONZAEMNMFQXRA-UHFFFAOYSA-N mirtazapine Chemical compound C1C2=CC=CN=C2N2CCN(C)CC2C2=CC=CC=C21 RONZAEMNMFQXRA-UHFFFAOYSA-N 0.000 description 2
- 230000002981 neuropathic effect Effects 0.000 description 2
- 208000021722 neuropathic pain Diseases 0.000 description 2
- 201000001119 neuropathy Diseases 0.000 description 2
- 230000007823 neuropathy Effects 0.000 description 2
- 229960002715 nicotine Drugs 0.000 description 2
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 229960005343 ondansetron Drugs 0.000 description 2
- 201000008482 osteoarthritis Diseases 0.000 description 2
- 208000033808 peripheral neuropathy Diseases 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 208000019899 phobic disease Diseases 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 208000028173 post-traumatic stress disease Diseases 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000000698 schizophrenic effect Effects 0.000 description 2
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 2
- 229960002646 scopolamine Drugs 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 230000013275 serotonin uptake Effects 0.000 description 2
- 231100000872 sexual dysfunction Toxicity 0.000 description 2
- 230000036299 sexual function Effects 0.000 description 2
- 230000006886 spatial memory Effects 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 230000016978 synaptic transmission, cholinergic Effects 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 150000003573 thiols Chemical class 0.000 description 2
- BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 2
- 230000007497 verbal memory Effects 0.000 description 2
- 230000001755 vocal effect Effects 0.000 description 2
- 230000003936 working memory Effects 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- CQSVBPFCYHGUJN-BTJKTKAUSA-N (z)-but-2-enedioic acid;1-[2-(2,4-dimethylphenyl)sulfanylphenyl]piperazine Chemical compound OC(=O)\C=C/C(O)=O.CC1=CC(C)=CC=C1SC1=CC=CC=C1N1CCNCC1 CQSVBPFCYHGUJN-BTJKTKAUSA-N 0.000 description 1
- XYGVIBXOJOOCFR-BTJKTKAUSA-N (z)-but-2-enedioic acid;8-chloro-6-(2-fluorophenyl)-1-methyl-4h-imidazo[1,5-a][1,4]benzodiazepine Chemical compound OC(=O)\C=C/C(O)=O.C12=CC(Cl)=CC=C2N2C(C)=NC=C2CN=C1C1=CC=CC=C1F XYGVIBXOJOOCFR-BTJKTKAUSA-N 0.000 description 1
- XIGAHNVCEFUYOV-BTJKTKAUSA-N (z)-but-2-enedioic acid;n-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-n-pyridin-2-ylcyclohexanecarboxamide Chemical compound OC(=O)\C=C/C(O)=O.COC1=CC=CC=C1N1CCN(CCN(C(=O)C2CCCCC2)C=2N=CC=CC=2)CC1 XIGAHNVCEFUYOV-BTJKTKAUSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- WMKGGPCROCCUDY-UHFFFAOYSA-N 1,5-diphenylpenta-1,4-dien-3-one Chemical compound C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 WMKGGPCROCCUDY-UHFFFAOYSA-N 0.000 description 1
- UGBLISDIHDMHJX-UHFFFAOYSA-N 1-(4-fluorophenyl)-4-[4-(2-methoxyphenyl)piperazin-1-yl]butan-1-one;hydrochloride Chemical compound [Cl-].COC1=CC=CC=C1N1CC[NH+](CCCC(=O)C=2C=CC(F)=CC=2)CC1 UGBLISDIHDMHJX-UHFFFAOYSA-N 0.000 description 1
- JOJYHYRCIYAVHN-UHFFFAOYSA-N 1-[2-(2,4-dimethylphenyl)sulfanylphenyl]piperazine;hydrochloride Chemical compound Cl.CC1=CC(C)=CC=C1SC1=CC=CC=C1N1CCNCC1 JOJYHYRCIYAVHN-UHFFFAOYSA-N 0.000 description 1
- BQOITUSTUYQBCY-UHFFFAOYSA-N 1-[2-(2,4-dimethylphenyl)sulfanylphenyl]piperazine;methanesulfonic acid Chemical compound CS(O)(=O)=O.CC1=CC(C)=CC=C1SC1=CC=CC=C1N1CCNCC1 BQOITUSTUYQBCY-UHFFFAOYSA-N 0.000 description 1
- DZYONJWDSULFLC-UHFFFAOYSA-N 1-[2-(2,4-dimethylphenyl)sulfanylphenyl]piperazine;nitric acid Chemical compound O[N+]([O-])=O.CC1=CC(C)=CC=C1SC1=CC=CC=C1N1CCNCC1 DZYONJWDSULFLC-UHFFFAOYSA-N 0.000 description 1
- QYDKMADPKYDSCP-UHFFFAOYSA-N 1-[2-(2,4-dimethylphenyl)sulfanylphenyl]piperazine;phosphoric acid Chemical compound OP(O)(O)=O.CC1=CC(C)=CC=C1SC1=CC=CC=C1N1CCNCC1 QYDKMADPKYDSCP-UHFFFAOYSA-N 0.000 description 1
- SBTDCSMXVFWQDA-UHFFFAOYSA-N 1-[2-(2,4-dimethylphenyl)sulfanylphenyl]piperazine;sulfuric acid Chemical compound OS(O)(=O)=O.CC1=CC(C)=CC=C1SC1=CC=CC=C1N1CCNCC1 SBTDCSMXVFWQDA-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- NDKJATAIMQKTPM-UHFFFAOYSA-N 2,3-dimethylbenzenethiol Chemical compound CC1=CC=CC(S)=C1C NDKJATAIMQKTPM-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
- 102000006902 5-HT2C Serotonin Receptor Human genes 0.000 description 1
- 108010072553 5-HT2C Serotonin Receptor Proteins 0.000 description 1
- 102100024959 5-hydroxytryptamine receptor 2C Human genes 0.000 description 1
- 101710138093 5-hydroxytryptamine receptor 2C Proteins 0.000 description 1
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 1
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
- 102000012440 Acetylcholinesterase Human genes 0.000 description 1
- 108010022752 Acetylcholinesterase Proteins 0.000 description 1
- 229940100578 Acetylcholinesterase inhibitor Drugs 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- 206010063659 Aversion Diseases 0.000 description 1
- 208000010392 Bone Fractures Diseases 0.000 description 1
- 206010006002 Bone pain Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- NTBZJLVREFKBQO-UHFFFAOYSA-N CC(C1=CC=CC(C(C)=C)=C1N(C1)C=C[N+]1(C(C(C(C)=C)=CC=C1)=C1C(C)=C)Cl)=C Chemical compound CC(C1=CC=CC(C(C)=C)=C1N(C1)C=C[N+]1(C(C(C(C)=C)=CC=C1)=C1C(C)=C)Cl)=C NTBZJLVREFKBQO-UHFFFAOYSA-N 0.000 description 1
- 208000011597 CGF1 Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 206010054089 Depressive symptom Diseases 0.000 description 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 1
- 206010013496 Disturbance in attention Diseases 0.000 description 1
- 206010013654 Drug abuse Diseases 0.000 description 1
- 208000010228 Erectile Dysfunction Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 235000011002 L(+)-tartaric acid Nutrition 0.000 description 1
- 239000001358 L(+)-tartaric acid Substances 0.000 description 1
- FEWJPZIEWOKRBE-LWMBPPNESA-N L-(+)-Tartaric acid Natural products OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-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
- 206010024453 Ligament sprain Diseases 0.000 description 1
- 208000008930 Low Back Pain Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 208000019022 Mood disease Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000029549 Muscle injury Diseases 0.000 description 1
- OKIZCWYLBDKLSU-UHFFFAOYSA-M N,N,N-Trimethylmethanaminium chloride Chemical compound [Cl-].C[N+](C)(C)C OKIZCWYLBDKLSU-UHFFFAOYSA-M 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 229940099433 NMDA receptor antagonist Drugs 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 208000000450 Pelvic Pain Diseases 0.000 description 1
- 208000004983 Phantom Limb Diseases 0.000 description 1
- 206010056238 Phantom pain Diseases 0.000 description 1
- 239000005922 Phosphane Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 206010037779 Radiculopathy Diseases 0.000 description 1
- 101100041796 Rattus norvegicus Slc6a4 gene Proteins 0.000 description 1
- 239000012891 Ringer solution Substances 0.000 description 1
- 208000010340 Sleep Deprivation Diseases 0.000 description 1
- 208000020307 Spinal disease Diseases 0.000 description 1
- 208000010040 Sprains and Strains Diseases 0.000 description 1
- 206010043220 Temporomandibular joint syndrome Diseases 0.000 description 1
- 208000008548 Tension-Type Headache Diseases 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
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 229940022698 acetylcholinesterase Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000003522 acrylic cement Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 206010001584 alcohol abuse Diseases 0.000 description 1
- 208000025746 alcohol use disease Diseases 0.000 description 1
- FLZQKRKHLSUHOR-UHFFFAOYSA-N alosetron Chemical compound CC1=NC=N[C]1CN1C(=O)C(C=2C(=CC=CC=2)N2C)=C2CC1 FLZQKRKHLSUHOR-UHFFFAOYSA-N 0.000 description 1
- 229960003550 alosetron Drugs 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 230000037007 arousal Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000003416 augmentation Effects 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
- 229960003237 betaine Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 230000001684 chronic effect Effects 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
- 230000007012 clinical effect Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 239000013078 crystal 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
- 230000007812 deficiency Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000000586 desensitisation Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 230000009699 differential effect Effects 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 238000001938 differential scanning calorimetry curve Methods 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 238000000835 electrochemical detection Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000010326 executive functioning Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry 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
- 125000005843 halogen group Chemical group 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000002657 hormone replacement therapy Methods 0.000 description 1
- GVLGAFRNYJVHBC-UHFFFAOYSA-N hydrate;hydrobromide Chemical compound O.Br GVLGAFRNYJVHBC-UHFFFAOYSA-N 0.000 description 1
- 201000001881 impotence Diseases 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000004898 kneading Methods 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000012035 limiting reagent Substances 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
- 230000007774 longterm Effects 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 229940057948 magnesium stearate Drugs 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 206010027175 memory impairment Diseases 0.000 description 1
- 230000005906 menstruation Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 239000004050 mood stabilizer Substances 0.000 description 1
- 229940127237 mood stabilizer Drugs 0.000 description 1
- 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 description 1
- 229960002362 neostigmine Drugs 0.000 description 1
- LULNWZDBKTWDGK-UHFFFAOYSA-M neostigmine bromide Chemical compound [Br-].CN(C)C(=O)OC1=CC=CC([N+](C)(C)C)=C1 LULNWZDBKTWDGK-UHFFFAOYSA-M 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- 230000002474 noradrenergic effect Effects 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 208000001797 obstructive sleep apnea Diseases 0.000 description 1
- 210000000287 oocyte Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- XYFCNXWJFGUGBZ-UHFFFAOYSA-N oxathiecane 2,2-dioxide Chemical compound O=S1(=O)CCCCCCCCO1 XYFCNXWJFGUGBZ-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 210000002741 palatine tonsil Anatomy 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- WEYVCQFUGFRXOM-UHFFFAOYSA-N perazine Chemical compound C1CN(C)CCN1CCCN1C2=CC=CC=C2SC2=CC=CC=C21 WEYVCQFUGFRXOM-UHFFFAOYSA-N 0.000 description 1
- 229960002195 perazine Drugs 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000001050 pharmacotherapy Methods 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 229910000064 phosphane Inorganic materials 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- PHUTUTUABXHXLW-UHFFFAOYSA-N pindolol Chemical compound CC(C)NCC(O)COC1=CC=CC2=NC=C[C]12 PHUTUTUABXHXLW-UHFFFAOYSA-N 0.000 description 1
- 229960002508 pindolol Drugs 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 230000004793 poor memory Effects 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940116317 potato starch Drugs 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000003414 procognitive effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 230000020341 sensory perception of pain Effects 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 230000004039 social cognition Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- 206010044652 trigeminal neuralgia Diseases 0.000 description 1
- 229940035722 triiodothyronine Drugs 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 230000031836 visual learning Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000008096 xylene Substances 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
- C07D295/08—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2009—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/16—Central respiratory analeptics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/10—Drugs for disorders of the urinary system of the bladder
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
- Y10T428/2982—Particulate matter [e.g., sphere, flake, etc.]
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Addiction (AREA)
- Psychiatry (AREA)
- Physical Education & Sports Medicine (AREA)
- Diabetes (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pulmonology (AREA)
- Hospice & Palliative Care (AREA)
- Heart & Thoracic Surgery (AREA)
- Immunology (AREA)
- Psychology (AREA)
- Urology & Nephrology (AREA)
- Cardiology (AREA)
- Emergency Medicine (AREA)
- Otolaryngology (AREA)
- Endocrinology (AREA)
- Child & Adolescent Psychology (AREA)
- Inorganic Chemistry (AREA)
Applications Claiming Priority (14)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US80501406P | 2006-06-16 | 2006-06-16 | |
| DKPA200600824 | 2006-06-16 | ||
| DK200600824 | 2006-06-16 | ||
| US805014P | 2006-06-16 | ||
| US82666606P | 2006-09-22 | 2006-09-22 | |
| DKPA200601223 | 2006-09-22 | ||
| US826666P | 2006-09-22 | ||
| DK200601223 | 2006-09-22 | ||
| US86282606P | 2006-10-25 | 2006-10-25 | |
| DKPA200601384 | 2006-10-25 | ||
| US862826P | 2006-10-25 | ||
| DK200601384 | 2006-10-25 | ||
| DK200700427 | 2007-03-20 | ||
| DKPA200700427 | 2007-03-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2432102T3 true ES2432102T3 (es) | 2013-11-29 |
Family
ID=39722479
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES11193235T Active ES2432102T3 (es) | 2006-06-16 | 2007-06-15 | Compuestos con actividad combinada en SERT, 5-HT3 y 5-HT1A |
| ES07764495T Active ES2379200T5 (es) | 2006-06-16 | 2007-06-15 | Bromhidrato de 1-[2-(2,4-Dimetilfenilsulfanil)fenil]piperazina como compuesto con recaptación de serotonina combinada con actividad 5-HT3 y 5-HT1A para el tratamiento del deterioro cognitivo |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES07764495T Active ES2379200T5 (es) | 2006-06-16 | 2007-06-15 | Bromhidrato de 1-[2-(2,4-Dimetilfenilsulfanil)fenil]piperazina como compuesto con recaptación de serotonina combinada con actividad 5-HT3 y 5-HT1A para el tratamiento del deterioro cognitivo |
Country Status (31)
| Country | Link |
|---|---|
| US (13) | US8722684B2 (enExample) |
| EP (2) | EP2439201B1 (enExample) |
| JP (8) | JP4590013B2 (enExample) |
| KR (3) | KR101445514B1 (enExample) |
| CN (3) | CN102614179B (enExample) |
| AR (1) | AR061481A1 (enExample) |
| AT (1) | ATE540941T1 (enExample) |
| AU (1) | AU2007260355B2 (enExample) |
| BR (3) | BR122020011920A2 (enExample) |
| CA (1) | CA2655212C (enExample) |
| CL (1) | CL2011001610A1 (enExample) |
| CY (1) | CY1112635T1 (enExample) |
| DK (1) | DK2044043T4 (enExample) |
| EA (1) | EA015287B1 (enExample) |
| ES (2) | ES2432102T3 (enExample) |
| FI (1) | FI2044043T5 (enExample) |
| HR (1) | HRP20120173T4 (enExample) |
| IL (1) | IL195511A (enExample) |
| MA (1) | MA30575B1 (enExample) |
| MX (1) | MX2008016141A (enExample) |
| MY (1) | MY150647A (enExample) |
| NO (1) | NO343929B1 (enExample) |
| NZ (1) | NZ572986A (enExample) |
| PL (1) | PL2044043T5 (enExample) |
| PT (1) | PT2044043E (enExample) |
| RS (1) | RS52205B2 (enExample) |
| SI (1) | SI2044043T2 (enExample) |
| TN (1) | TNSN08460A1 (enExample) |
| TW (1) | TWI443091B (enExample) |
| WO (1) | WO2007144005A1 (enExample) |
| ZA (1) | ZA200810017B (enExample) |
Families Citing this family (117)
| 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 |
| 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 |
| BR122020011920A2 (pt) | 2006-06-16 | 2020-08-25 | Lundbeck & Co As H | composto, composição farmacêutica, método para tratar uma doença, uso de um composto, e processos para a preparação de um composto, e para a fabricação de um composto |
| TW200848411A (en) * | 2007-03-20 | 2008-12-16 | Lundbeck & Co As H | Novel therapeutic uses of 1-[2-(2, 4-dimethylphenylsulfanyl)phenyl]-piperazine |
| 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 |
| TW201033181A (en) * | 2009-02-17 | 2010-09-16 | Lundbeck & Co As H | Purification of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine |
| GEP20135938B (en) * | 2009-04-24 | 2013-10-10 | H Lundbeck As | Liquid pharmaceutical formulations of 1-[2-(2,4-dimethylsulfanyl)phenyl]piperazine |
| MX2012002199A (es) * | 2009-08-24 | 2012-03-16 | Lundbeck & Co As H | Nuevas composiciones de 1-[2-(2,4-dimetil-fenilsulfanil)-fenil]pip erazina. |
| WO2011136376A1 (ja) * | 2010-04-30 | 2011-11-03 | 武田薬品工業株式会社 | 腸溶性錠剤 |
| PL3650439T3 (pl) * | 2010-07-23 | 2021-06-28 | Grünenthal GmbH | Sole lub kokryształy 3-(3-dimetyloamino-1-etylo-2-metylo-propylo)-fenolu |
| TW201212918A (en) | 2010-08-23 | 2012-04-01 | Lundbeck & Co As H | Therapeutic uses of 1-[2-(2,4-dimethyl-phenylsulfanyl)phenyl]piperazine |
| LT2800746T (lt) * | 2012-01-03 | 2019-06-10 | H. Lundbeck A/S | 1-[2-(2,4-dimetil-fenilsulfanil)-fenil]-piperazino gavimo būdas |
| US9713594B2 (en) * | 2012-09-11 | 2017-07-25 | Bend Research, Inc. | Methods for making pharmaceutical solid dosage forms of spray-dried dispersions |
| 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 |
| CN104853755B (zh) * | 2012-12-13 | 2017-08-22 | H.隆德贝克有限公司 | 包含沃替西汀和多奈哌齐的组合物 |
| CN104995181B (zh) * | 2013-02-22 | 2017-03-08 | H.隆德贝克有限公司 | 沃替西汀生产方法 |
| EP2981520B1 (en) | 2013-04-04 | 2019-03-06 | LEK Pharmaceuticals d.d. | New process for the synthesis of 1-(2-((2,4-dimethylphenyl)thio)phenyl)piperazine |
| WO2014177491A1 (en) | 2013-04-29 | 2014-11-06 | Lek Pharmaceuticals D.D. | New solid form of 1-(2-((2,4-dimethylphenyl)thio)phenyl)piperazine hydrobromide |
| WO2014191548A1 (en) * | 2013-05-31 | 2014-12-04 | Lek Pharmaceuticals D.D. | New process for the synthesis of 1-(2-((2,4-dimethylphenyl)thio)phenyl)piperazine |
| AU2014286308B2 (en) * | 2013-07-01 | 2018-05-10 | Lek Pharmaceuticals D.D. | 1-[2-(2,4-dimethylphenylsulfanyl) phenyl]piperazine acetate in crystalline form |
| US20160200698A1 (en) * | 2013-09-12 | 2016-07-14 | Hangzhou Pushai Pharmaceutical Technology Co., Ltd | Vortioxetine salt and crystal thereof, their preparation method, pharmaceutical compositions and usage |
| WO2015044963A1 (en) | 2013-09-30 | 2015-04-02 | Cadila Healthcare Limited | An amorphous vortioxetine and salts thereof |
| CN104650003A (zh) * | 2013-11-22 | 2015-05-27 | 天津市汉康医药生物技术有限公司 | 一种沃替西汀化合物 |
| EP2878596A1 (en) * | 2013-11-29 | 2015-06-03 | LEK Pharmaceuticals d.d. | Synthesis of vortioxetine via (2-(piperazine-1-yl)phenyl)lithium intermediates |
| CA2933733A1 (en) | 2013-12-20 | 2015-06-25 | Connie Sanchez Morillo | 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 |
| CN103788020B (zh) * | 2014-01-22 | 2015-11-04 | 苏州明锐医药科技有限公司 | 沃替西汀的制备方法 |
| 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 |
| WO2015114395A1 (en) | 2014-01-31 | 2015-08-06 | Egis Gyógyszergyár Zrt. | Process for the preparation of vortioxetine salts |
| EP3114239A4 (en) * | 2014-03-05 | 2017-10-11 | Takeda Pharmaceutical Company Limited | Method for treating depression and major depressive disorder |
| EP2930171A1 (en) | 2014-04-07 | 2015-10-14 | LEK Pharmaceuticals d.d. | Synthesis of vortioxetine via (2,4-dimethylphenyl)(2-iodophenyl)sulfane intermediate |
| CN104974110A (zh) * | 2014-04-10 | 2015-10-14 | 江苏豪森药业股份有限公司 | 1-[2-(2,4-二甲基苯基硫基)苯基]哌嗪氢溴酸盐的新晶型及其制备方法和用途 |
| EP3137083A2 (en) * | 2014-04-28 | 2017-03-08 | Alembic Pharmaceuticals Limited | Novel polymorphic forms of vortioxetine and its pharmaceutically acceptable salts |
| CN105254590B (zh) * | 2014-05-09 | 2019-09-03 | 江苏豪森药业集团有限公司 | 沃替西汀氢溴酸盐晶型及其制备方法和用途 |
| 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 |
| CN105198837B (zh) * | 2014-06-09 | 2018-05-04 | 上海医药工业研究院 | 一种沃替西汀氢溴酸盐晶体及其制备方法 |
| CN105218482B (zh) * | 2014-06-24 | 2018-04-06 | 杭州和泽医药科技有限公司 | 沃替西汀氢溴酸盐β晶型的制备方法 |
| 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 |
| CN105330614A (zh) * | 2014-08-04 | 2016-02-17 | 上海诺星医药科技有限公司 | 一种氢溴酸沃替西汀晶体及其制备方法 |
| CN104119299B (zh) * | 2014-08-13 | 2016-08-17 | 北京蓝贝望生物医药科技股份有限公司 | 沃赛汀或沃替西汀的氢溴酸盐 |
| CN104119298B (zh) * | 2014-08-13 | 2016-08-24 | 北京蓝贝望生物医药科技股份有限公司 | 氢溴酸沃赛汀或氢溴酸沃替西汀 |
| 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 |
| US20170333424A1 (en) * | 2014-10-24 | 2017-11-23 | Hexal Ag | Amorphous Vortioxetine Hydrobromide |
| CN105669594A (zh) * | 2014-11-19 | 2016-06-15 | 康普药业股份有限公司 | 抗抑郁症药1-[2-(2,4-二甲基苯基硫基)苯基]哌嗪的制备方法 |
| 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 |
| CN104356092B (zh) * | 2014-11-27 | 2017-03-22 | 合肥创新医药技术有限公司 | 沃替西汀的制备方法 |
| 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 |
| CN105777667A (zh) * | 2014-12-18 | 2016-07-20 | 康普药业股份有限公司 | 抗抑郁症药1-[2-(2,4-二甲基苯基硫基)苯基]哌嗪的制备方法 |
| CN105801517A (zh) * | 2014-12-30 | 2016-07-27 | 上海奥博生物医药技术有限公司 | 一种沃替西汀氢溴酸盐新晶型及其制备方法 |
| 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 |
| CN104644594A (zh) * | 2015-02-03 | 2015-05-27 | 郑州大明药物科技有限公司 | 一种氢溴酸沃替西汀胃溶片及其制备方法 |
| 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 |
| AU2016224930A1 (en) | 2015-02-25 | 2017-09-07 | Lupin Limited | Process for the preparation of Vortioxetine |
| CN104650004B (zh) * | 2015-03-06 | 2017-06-06 | 中山万汉制药有限公司 | 一种氢溴酸沃替西汀的制备方法 |
| CN104628677A (zh) * | 2015-03-16 | 2015-05-20 | 浙江大学 | 一种沃替西汀有机酸盐晶型及其制备方法 |
| EP3274330A1 (en) | 2015-03-26 | 2018-01-31 | Cipla Limited | Method for making serotonin reuptake inhibitors |
| CN105367515B (zh) * | 2015-05-08 | 2017-10-27 | 北京北陆药业股份有限公司 | 一种氢溴酸沃替西汀α晶型的制备方法 |
| CN106279065A (zh) * | 2015-05-12 | 2017-01-04 | 北京深蓝海生物医药科技有限公司 | 一种氢溴酸沃替西汀的精制转晶方法 |
| JO3456B1 (ar) * | 2015-05-13 | 2020-07-05 | H Lundbeck As | فيروتيوكسيتين بيروجلوتامات |
| CN104910099B (zh) * | 2015-05-22 | 2017-03-08 | 扬子江药业集团有限公司 | 一种氢溴酸沃替西汀晶体的制备方法 |
| CN106316986B (zh) * | 2015-07-03 | 2019-02-05 | 成都弘达药业有限公司 | 一种1-[2-(2,4-二甲基苯基硫烷基)苯基]哌嗪氢溴酸盐α型晶体的制备方法 |
| CN105111167A (zh) * | 2015-08-06 | 2015-12-02 | 华南理工大学 | 一种沃替西汀半盐酸盐及其制备方法和药物组合物 |
| CN105061364A (zh) * | 2015-08-17 | 2015-11-18 | 河北国龙制药有限公司 | 氢溴酸沃替西汀的制备方法 |
| EP3337789A1 (en) * | 2015-08-19 | 2018-06-27 | Amneal Pharmaceuticals Company GmbH | Process for preparation of vortioxetine hydrobromide |
| CN105153066B (zh) * | 2015-09-07 | 2018-01-09 | 浙江大学 | 盐酸沃替西汀的结晶型物及其制备方法 |
| CN106632145B (zh) * | 2015-11-04 | 2021-11-05 | 江苏豪森药业集团有限公司 | 沃替西汀氢溴酸盐晶型α的新制备方法 |
| CN106674153A (zh) * | 2015-11-05 | 2017-05-17 | 浙江京新药业股份有限公司 | 沃替西汀半盐酸盐晶体及其组合物与制备和应用 |
| CN105294554B (zh) * | 2015-11-18 | 2017-11-07 | 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 |
| GB2557867A (en) * | 2015-11-18 | 2018-07-04 | Azad Pharmaceutical Ingredients Ag | New synthetic path to vortioxetine salts |
| US11013830B2 (en) * | 2015-11-20 | 2021-05-25 | Institut Pasteur | 5-hydroxytryptamine 1B receptor-stimulating agent for enhancing in vivo engraftment potential |
| EP3184102A1 (en) | 2015-12-23 | 2017-06-28 | Hexal AG | Pharmaceutical composition of vortioxetine hydrobromide comprising an inert core formed of an acidic reacting compound |
| EP3184104B1 (en) | 2015-12-23 | 2018-09-12 | Hexal AG | Pharmaceutical composition of vortioxetine hydrobromide comprising vortioxetine hydrobromide in a polyethylene oxide matrix |
| US20190194154A1 (en) * | 2016-01-20 | 2019-06-27 | Amneal Pharmaceuticals Company Gmbh | Polymorphic Forms Of Vortioxetine Hydrobromide Tert-Butanolate |
| WO2017154016A1 (en) * | 2016-03-07 | 2017-09-14 | Msn Laboratories Private Limited | Novel crystalline polymorphs of 1-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]-piperazine hydrobromide and process for preparation thereof |
| WO2017162536A1 (en) | 2016-03-21 | 2017-09-28 | H. Lundbeck A/S | Vortioxetine prodrugs |
| CA3018402C (en) * | 2016-03-29 | 2021-05-11 | Shanghai Synergy Pharmaceutical Sciences Co., Ltd | Vortioxetine pamoic acid salt and crystal form thereof |
| WO2017215636A1 (zh) * | 2016-06-16 | 2017-12-21 | 广东东阳光药业有限公司 | 二芳基硫醚哌嗪类化合物及其制备方法和用途 |
| MA45532A (fr) | 2016-07-01 | 2019-05-08 | H Lundbeck As | Schémas posologiques de la vortioxétine destinés à une apparition rapide de l'effet antidépresseur |
| US20190290641A1 (en) * | 2016-07-15 | 2019-09-26 | Institut Pasteur | 5-hydroxytryptamine 1b receptor-stimulating agent for skin and/or hair repair |
| CN106243062A (zh) * | 2016-07-31 | 2016-12-21 | 合肥远志医药科技开发有限公司 | 一种沃替西汀工业化生产方法 |
| US20190224192A1 (en) | 2016-08-29 | 2019-07-25 | Cipla Limited | Stable Pharmaceutical Composition of Vortioxetine Hydrobromide |
| WO2018065348A1 (en) | 2016-10-05 | 2018-04-12 | Hexal Ag | Novel enteric-coated tablet comprising vortioxetine |
| CN107954947A (zh) * | 2016-10-14 | 2018-04-24 | 北京莱瑞森医药科技有限公司 | 沃替西汀氢溴酸盐晶型c及其制备方法 |
| US10519121B2 (en) | 2016-12-30 | 2019-12-31 | Apicore Us Llc | Process and novel polymorphic form of vortioxetine and its pharmaceutically acceptable salts |
| US10428033B2 (en) | 2017-02-15 | 2019-10-01 | Piramal Enterprises Limited | Process for the preparation of vortioxetine and salts thereof |
| US11020390B2 (en) * | 2017-02-17 | 2021-06-01 | 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 |
| KR102551433B1 (ko) | 2017-04-25 | 2023-07-04 | 하. 룬드벡 아크티에셀스카브 | 보르티옥세틴 hbr 알파-형태의 제조 방법 |
| 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 |
| CN109503517A (zh) * | 2017-09-14 | 2019-03-22 | 万全万特制药（厦门）有限公司 | 一种沃替西汀α晶型的制备方法 |
| JP6876586B2 (ja) * | 2017-09-27 | 2021-05-26 | Ｔｏｗａ株式会社 | 加工装置 |
| CN109928941A (zh) * | 2017-12-19 | 2019-06-25 | 成都弘达药业有限公司 | 一种氢溴酸沃替西汀的结晶化合物及其制备方法 |
| 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 |
| US10111873B1 (en) | 2018-01-17 | 2018-10-30 | King Saud University | Dihydropyrimidinone derivatives |
| EP3762371A1 (en) * | 2018-02-06 | 2021-01-13 | Piramal Enterprises Limited | An improved process for the preparation of vortioxetine and salts thereof |
| WO2020087031A1 (en) | 2018-10-26 | 2020-04-30 | The Research Foundation For The State University Of New York | Combination serotonin specific reuptake inhibitor and serotonin 1a receptor partial agonist for reducing l-dopa-induced dyskinesia |
| CN109535050A (zh) * | 2018-12-14 | 2019-03-29 | 合肥创新医药技术有限公司 | 一种1,2-双（（2,4-二甲基苯基）硫基）苯的制备方法 |
| JP2022540249A (ja) | 2019-09-04 | 2022-09-14 | シーズンズ バイオテクノロジー （タイジョウ） カンパニー リミテッド | ボルチオキセチン臭化水素酸塩を含む口腔内味マスキング用コーティング顆粒、固体分散体及び製剤 |
| TR202001040A2 (tr) * | 2020-01-23 | 2021-07-26 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | Vorti̇okseti̇n hi̇drobromi̇di̇n kri̇stali̇n c formu |
| 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 |
| KR102455000B1 (ko) | 2020-07-06 | 2022-10-17 | 원광대학교산학협력단 | 피페라진 화합물 및 이의 제조 방법 |
| CN112006995A (zh) * | 2020-08-14 | 2020-12-01 | 石药集团中奇制药技术（石家庄）有限公司 | 一种氢溴酸伏硫西汀片的制备方法 |
| CN114075154B (zh) * | 2020-08-20 | 2025-03-28 | 正大天晴药业集团股份有限公司 | 伏硫西汀的制备方法 |
| US12281088B2 (en) | 2020-09-10 | 2025-04-22 | Suzhou Fude Zhaofeng Biochemical Technology Co., Ltd | Process for the synthesis of vortioxetine |
| CN112125868B (zh) * | 2020-09-25 | 2021-08-03 | 中山万远新药研发有限公司 | 一种氢溴酸伏硫西汀晶型及其制备方法、组合物与用途 |
| WO2023036820A1 (en) | 2021-09-10 | 2023-03-16 | H. Lundbeck A/S | Therapeutic uses of 1-[2-(2,4-dimethyl-phenylsulfanyl)phenyl]piperazine |
| CN116836132A (zh) * | 2022-03-23 | 2023-10-03 | 浙江华海药业股份有限公司 | 一种沃替西汀氢溴酸盐晶型h及其制备方法和用途 |
| CN115160258B (zh) * | 2022-06-24 | 2023-11-17 | 辰欣药业股份有限公司 | 一种氢溴酸沃替西汀γ晶型的制备方法 |
| GB2622880A (en) | 2022-09-30 | 2024-04-03 | Alkaloid Ad Skopje | Palatable orodispersible formulation of vortioxetine |
| JP7632902B2 (ja) | 2023-02-10 | 2025-02-19 | 株式会社Dhq | タキシフォリン含有組成物 |
| CN116589434A (zh) * | 2023-05-22 | 2023-08-15 | 山东泰合医药科技有限公司 | 一种伏硫西汀昔萘酸盐晶型a及其制备方法与应用 |
| 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 (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4727064A (en) | 1984-04-25 | 1988-02-23 | The United States Of America As Represented By The Department Of Health And Human Services | Pharmaceutical preparations containing cyclodextrin derivatives |
| WO1994020091A1 (en) | 1993-03-05 | 1994-09-15 | Hexal Pharma Gmbh | Crystalline cyclodextrin inclusion complexes of ranitidine hydrochloride and process for their preparation |
| JPH07110050A (ja) | 1993-10-13 | 1995-04-25 | Daikin Mfg Co Ltd | 捩じり振動減衰装置 |
| ATE294778T1 (de) | 1995-01-23 | 2005-05-15 | Daiichi Suntory Pharma Co Ltd | Verbesserung oder heilung von durch ischämischen krankheiten hervorgerufenen symtomen und dafür verwendbare phenylpiperidinverbingungen |
| AU4918796A (en) | 1995-02-10 | 1996-08-27 | Eli Lilly And Company | Methods of treating or preventing psychiatric disorders |
| ES2193607T3 (es) | 1998-01-16 | 2003-11-01 | Hoffmann La Roche | Derivados de benzosulfona . |
| WO1999061027A1 (en) | 1998-05-22 | 1999-12-02 | Eli Lilly And Company | Combination therapy for treatment of refractory depression |
| JP5035813B2 (ja) | 1998-07-10 | 2012-09-26 | マサチューセッツ インスティテュート オブ テクノロジー | 金属用のリガンドおよびそれらに基づいて改善された金属触媒法 |
| ES2154605B1 (es) | 1999-09-14 | 2001-11-16 | Univ Madrid Complutense | Nuevos derivados mixtos de bencimidazol-arilpiperazina con afinidad por los receptores serotoninergicos 5-ht1a y 5-ht3 |
| UA77650C2 (en) | 1999-12-06 | 2007-01-15 | Lundbeck & Co As H | Use of serotonin reuptake inhibitor in combination with deramcyclane |
| MXPA02006223A (es) | 1999-12-30 | 2002-12-05 | Lundbeck & Co As H | Derivados de fenilpiperazina sustituida, su preparcion y uso. |
| PE20020063A1 (es) | 2000-06-20 | 2002-01-30 | Upjohn Co | Bis-arilsulfonas como ligandos del receptor de 5-ht |
| UA76130C2 (en) | 2000-11-20 | 2006-07-17 | Merck Patent Gmbh | Use of compounds combining properties of selective inhibitors of serotonin re-uptake and agonists of 5-ht1a receptor for treatment of irritable bowel syndrome |
| ATE340786T1 (de) | 2000-11-28 | 2006-10-15 | Pfizer Prod Inc | Salze eines 4-isothiazolcarboxamids und ihre verwendung als anti-hyperproliferationsmittel |
| UA81749C2 (uk) | 2001-10-04 | 2008-02-11 | Х. Луннбек А/С | Фенілпіперазинові похідні як інгібітори зворотного захоплення серотоніну |
| DE60219521T2 (de) | 2001-12-20 | 2007-08-16 | H. Lundbeck A/S | Aryloxyphenyl und arylsulfanylphenylderivate |
| AU2003236500B9 (en) | 2002-06-12 | 2009-07-02 | Chemocentryx, Inc. | 1-aryl-4-substituted piperazine derivatives for use as CCR1 antagonists for the treatment of inflammation and immune disorders |
| CA2521258C (en) * | 2003-04-04 | 2009-12-01 | H. Lundbeck A/S | 4-(2-phenylsulfanyl-phenyl)-piperidine derivatives as serotonin reuptake inhibitors |
| US9029363B2 (en) * | 2003-04-30 | 2015-05-12 | Boehringer Ingelheim International Gmbh | Telmisartan sodium salt pharmaceutical formulation |
| US7893261B2 (en) | 2004-03-26 | 2011-02-22 | Baylor University | Serotonin reuptake inhibitors |
| EP1846359A4 (en) | 2005-01-06 | 2010-03-31 | Cj Cheiljedang Corp | INORGANIC ACID SALTS OF SIBUTRAMINE |
| CN1270776C (zh) | 2005-05-08 | 2006-08-23 | 纪辉 | 治疗粘膜溃疡的药物组合物，其制备和用途 |
| AU2007260356B2 (en) | 2006-06-16 | 2013-01-24 | 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 |
| BR122020011920A2 (pt) | 2006-06-16 | 2020-08-25 | Lundbeck & Co As H | composto, composição farmacêutica, método para tratar uma doença, uso de um composto, e processos para a preparação de um composto, e para a fabricação de um composto |
| TW200848411A (en) * | 2007-03-20 | 2008-12-16 | Lundbeck & Co As H | Novel therapeutic uses of 1-[2-(2, 4-dimethylphenylsulfanyl)phenyl]-piperazine |
| 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 |
| 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 |
-
2007
- 2007-06-15 BR BR122020011920A patent/BR122020011920A2/pt not_active Application Discontinuation
- 2007-06-15 ZA ZA200810017A patent/ZA200810017B/xx unknown
- 2007-06-15 KR KR1020137013877A patent/KR101445514B1/ko active Active
- 2007-06-15 WO PCT/DK2007/050075 patent/WO2007144005A1/en not_active Ceased
- 2007-06-15 MX MX2008016141A patent/MX2008016141A/es active IP Right Grant
- 2007-06-15 PL PL07764495T patent/PL2044043T5/pl unknown
- 2007-06-15 PT PT07764495T patent/PT2044043E/pt unknown
- 2007-06-15 EP EP11193235.6A patent/EP2439201B1/en active Active
- 2007-06-15 BR BR122020011899-7A patent/BR122020011899B1/pt active IP Right Grant
- 2007-06-15 AT AT07764495T patent/ATE540941T1/de active
- 2007-06-15 AU AU2007260355A patent/AU2007260355B2/en active Active
- 2007-06-15 US US12/301,061 patent/US8722684B2/en active Active
- 2007-06-15 ES ES11193235T patent/ES2432102T3/es active Active
- 2007-06-15 RS RS20120107A patent/RS52205B2/sr unknown
- 2007-06-15 KR KR1020087030668A patent/KR20090028712A/ko not_active Ceased
- 2007-06-15 CA CA2655212A patent/CA2655212C/en active Active
- 2007-06-15 AR ARP070102641A patent/AR061481A1/es active IP Right Grant
- 2007-06-15 NZ NZ572986A patent/NZ572986A/en unknown
- 2007-06-15 EP EP07764495.3A patent/EP2044043B2/en active Active
- 2007-06-15 BR BRPI0713425-8A patent/BRPI0713425A2/pt not_active Application Discontinuation
- 2007-06-15 MY MYPI20084778 patent/MY150647A/en unknown
- 2007-06-15 SI SI200730876T patent/SI2044043T2/sl unknown
- 2007-06-15 CN CN201210034695.6A patent/CN102614179B/zh active Active
- 2007-06-15 KR KR1020137029366A patent/KR101627901B1/ko active Active
- 2007-06-15 HR HRP20120173TT patent/HRP20120173T4/hr unknown
- 2007-06-15 CN CN2007800223385A patent/CN101472906B/zh active Active
- 2007-06-15 FI FIEP07764495.3T patent/FI2044043T5/fi active
- 2007-06-15 DK DK07764495.3T patent/DK2044043T4/da active
- 2007-06-15 ES ES07764495T patent/ES2379200T5/es active Active
- 2007-06-15 EA EA200970018A patent/EA015287B1/ru active Protection Beyond IP Right Term
- 2007-06-15 JP JP2009514642A patent/JP4590013B2/ja active Active
- 2007-06-15 CN CN201210034684.8A patent/CN102617513B/zh active Active
- 2007-06-20 TW TW096122001A patent/TWI443091B/zh active
-
2008
- 2008-11-17 TN TNP2008000460A patent/TNSN08460A1/en unknown
- 2008-11-25 IL IL195511A patent/IL195511A/en active IP Right Grant
-
2009
- 2009-01-06 MA MA31550A patent/MA30575B1/fr unknown
- 2009-01-16 NO NO20090229A patent/NO343929B1/no active IP Right Maintenance
- 2009-12-25 JP JP2009295187A patent/JP5702929B2/ja active Active
-
2011
- 2011-06-29 CL CL2011001610A patent/CL2011001610A1/es unknown
-
2012
- 2012-03-08 CY CY20121100240T patent/CY1112635T1/el unknown
- 2012-11-28 JP JP2012259835A patent/JP5763609B2/ja active Active
-
2014
- 2014-04-01 US US14/242,337 patent/US9227946B2/en active Active
- 2014-04-01 US US14/242,510 patent/US9125908B2/en active Active
- 2014-04-29 US US14/264,373 patent/US9101626B2/en active Active
- 2014-07-09 US US14/326,725 patent/US9125909B2/en active Active
- 2014-08-29 US US14/472,896 patent/US9095588B2/en active Active
- 2014-09-09 US US14/481,000 patent/US9125910B2/en active Active
- 2014-09-09 US US14/480,949 patent/US8969355B2/en active Active
-
2015
- 2015-06-11 JP JP2015118179A patent/JP6101742B2/ja active Active
- 2015-11-23 US US14/948,775 patent/US20160083359A1/en not_active Abandoned
-
2016
- 2016-08-19 JP JP2016161018A patent/JP2017008086A/ja not_active Withdrawn
-
2017
- 2017-08-10 US US15/674,043 patent/US9861630B1/en active Active
- 2017-12-18 US US15/845,677 patent/US20180333408A1/en not_active Abandoned
-
2018
- 2018-08-09 JP JP2018150653A patent/JP6724082B2/ja active Active
-
2019
- 2019-07-03 US US16/502,677 patent/US11458134B2/en active Active
-
2022
- 2022-09-20 US US17/949,188 patent/US20230021520A1/en active Pending
- 2022-11-15 JP JP2022182209A patent/JP2023009175A/ja not_active Withdrawn
-
2024
- 2024-10-31 JP JP2024191303A patent/JP2025021476A/ja active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2432102T3 (es) | Compuestos con actividad combinada en SERT, 5-HT3 y 5-HT1A | |
| JP7179035B2 (ja) | 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 | |
| AU2017251723A1 (en) | 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl] piperazine as a compound with combined serotonin reuptake, 5-HT3 and 5-HT1A activity for the treatment of cognitive impairment |