PH26582A - Tertiary alkyl functionalized piperazine derivatives - Google Patents

Tertiary alkyl functionalized piperazine derivatives Download PDF

Info

Publication number: PH26582A
Authority: PH; Philippines
Prior art keywords: compound; carbon atoms; pharmaceutically acceptable; methoxyphenyl; acceptable salt
Prior art date: 1989-04-22

Application number

PH40415A

Other languages

English (en)

Inventor

Magid Abdel Abou-Gharbia

John P Yardley

Ian Anthony Cliffe

Original Assignee

American Home Prod

Ian Anthony Cliffe

Priority date (The priority date 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 date listed.)

1989-04-22

Filing date

1990-04-24

Publication date

1992-08-19

1989-04-22 Priority claimed from GB898909209A external-priority patent/GB8909209D0/en

1990-04-24 Application filed by American Home Prod, Ian Anthony Cliffe filed Critical American Home Prod

1992-08-19 Publication of PH26582A publication Critical patent/PH26582A/en

Links

125000000217 alkyl group Chemical group 0.000 title claims abstract description 46
150000004885 piperazines Chemical class 0.000 title description 2
229940066771 systemic antihistamines piperazine derivative Drugs 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 110
150000003839 salts Chemical class 0.000 claims abstract description 47
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 36
-1 polymethylene Polymers 0.000 claims abstract description 36
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 26
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 20
239000001257 hydrogen Substances 0.000 claims abstract description 20
125000003545 alkoxy group Chemical group 0.000 claims abstract description 12
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 11
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 11
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims abstract description 11
125000001424 substituent group Chemical group 0.000 claims abstract description 9
125000003282 alkyl amino group Chemical group 0.000 claims abstract description 6
125000005518 carboxamido group Chemical group 0.000 claims abstract description 6
125000004663 dialkyl amino group Chemical group 0.000 claims abstract description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 6
125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims abstract description 6
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 6
125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 5
125000001475 halogen functional group Chemical group 0.000 claims abstract 7
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 4
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 71
125000004432 carbon atom Chemical group C* 0.000 claims description 66
239000002253 acid Substances 0.000 claims description 18
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 11
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 claims description 10
125000004193 piperazinyl group Chemical group 0.000 claims description 9
150000002148 esters Chemical class 0.000 claims description 8
229910052799 carbon Inorganic materials 0.000 claims description 7
GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
150000003857 carboxamides Chemical class 0.000 claims description 5
QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 claims description 4
125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
125000004429 atom Chemical group 0.000 claims description 3
KTUWPDGCHSLGPA-UHFFFAOYSA-N 1-methyl-n-[2-(4-pyrimidin-2-ylpiperazin-1-yl)ethyl]cyclohexane-1-carboxamide Chemical compound C1CN(C=2N=CC=CN=2)CCN1CCNC(=O)C1(C)CCCCC1 KTUWPDGCHSLGPA-UHFFFAOYSA-N 0.000 claims description 2
YKORCGZHWBMXPT-UHFFFAOYSA-N 3-[4-(2-methoxyphenyl)piperazin-1-yl]-n-(1-methylcyclohexyl)propanamide Chemical compound COC1=CC=CC=C1N1CCN(CCC(=O)NC2(C)CCCCC2)CC1 YKORCGZHWBMXPT-UHFFFAOYSA-N 0.000 claims description 2
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims description 2
IDOBGLXAHFHSRR-OAHLLOKOSA-N n-[(2r)-1-[4-(2-methoxyphenyl)piperazin-1-yl]propan-2-yl]-2,2-dimethylpropanamide Chemical compound COC1=CC=CC=C1N1CCN(C[C@@H](C)NC(=O)C(C)(C)C)CC1 IDOBGLXAHFHSRR-OAHLLOKOSA-N 0.000 claims description 2
YNJCAZOZKRWGKA-UHFFFAOYSA-N n-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]-2,2-dimethylpropanamide Chemical compound COC1=CC=CC=C1N1CCN(CCCCNC(=O)C(C)(C)C)CC1 YNJCAZOZKRWGKA-UHFFFAOYSA-N 0.000 claims description 2
BYALYOPMENMMGY-UHFFFAOYSA-N n-tert-butyl-3-[4-(2-methoxyphenyl)piperazin-1-yl]propanamide Chemical compound COC1=CC=CC=C1N1CCN(CCC(=O)NC(C)(C)C)CC1 BYALYOPMENMMGY-UHFFFAOYSA-N 0.000 claims description 2
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
235000019260 propionic acid Nutrition 0.000 claims description 2
125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims 1
UMTDAKAAYOXIKU-UHFFFAOYSA-N N-tert-butyl-3-[4-(2-methoxyphenyl)-1-piperazinyl]-2-phenylpropanamide Chemical compound COC1=CC=CC=C1N1CCN(CC(C(=O)NC(C)(C)C)C=2C=CC=CC=2)CC1 UMTDAKAAYOXIKU-UHFFFAOYSA-N 0.000 claims 1
241000282320 Panthera leo Species 0.000 claims 1
NEGSDHFSOGWFNM-UHFFFAOYSA-N [2-[4-(2-methoxyphenyl)piperazin-1-yl]-1-phenylethyl] 2,2-dimethylpropanoate Chemical compound COC1=CC=CC=C1N1CCN(CC(OC(=O)C(C)(C)C)C=2C=CC=CC=2)CC1 NEGSDHFSOGWFNM-UHFFFAOYSA-N 0.000 claims 1
125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 claims 1
SQXIDCRJWUFDPX-UHFFFAOYSA-N n-tert-butyl-3-(4-pyrimidin-2-ylpiperazin-1-yl)propanamide Chemical compound C1CN(CCC(=O)NC(C)(C)C)CCN1C1=NC=CC=N1 SQXIDCRJWUFDPX-UHFFFAOYSA-N 0.000 claims 1
150000002431 hydrogen Chemical class 0.000 abstract description 6
239000000935 antidepressant agent Substances 0.000 abstract description 5
239000002249 anxiolytic agent Substances 0.000 abstract description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 3
230000001430 anti-depressive effect Effects 0.000 abstract description 2
229940005513 antidepressants Drugs 0.000 abstract description 2
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 91
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 75
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 63
239000000243 solution Substances 0.000 description 63
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 46
229910001868 water Inorganic materials 0.000 description 41
238000000921 elemental analysis Methods 0.000 description 38
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 32
235000019439 ethyl acetate Nutrition 0.000 description 31
239000000203 mixture Substances 0.000 description 31
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
239000000047 product Substances 0.000 description 27
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 25
239000012458 free base Substances 0.000 description 22
239000003921 oil Substances 0.000 description 22
235000019198 oils Nutrition 0.000 description 22
229960004132 diethyl ether Drugs 0.000 description 21
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
229940086542 triethylamine Drugs 0.000 description 21
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 16
229910000041 hydrogen chloride Inorganic materials 0.000 description 16
238000000034 method Methods 0.000 description 16
239000007787 solid Substances 0.000 description 16
239000000725 suspension Substances 0.000 description 16
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 13
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
239000013078 crystal Substances 0.000 description 11
239000007788 liquid Substances 0.000 description 11
239000011541 reaction mixture Substances 0.000 description 11
239000000741 silica gel Substances 0.000 description 11
229910002027 silica gel Inorganic materials 0.000 description 11
229910052943 magnesium sulfate Inorganic materials 0.000 description 10
235000019341 magnesium sulphate Nutrition 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
238000006243 chemical reaction Methods 0.000 description 9
238000001704 evaporation Methods 0.000 description 9
230000008020 evaporation Effects 0.000 description 9
239000002904 solvent Substances 0.000 description 9
239000012043 crude product Substances 0.000 description 8
238000004128 high performance liquid chromatography Methods 0.000 description 8
102000005962 receptors Human genes 0.000 description 8
108020003175 receptors Proteins 0.000 description 8
VNZLQLYBRIOLFZ-UHFFFAOYSA-N 1-(2-methoxyphenyl)piperazine Chemical compound COC1=CC=CC=C1N1CCNCC1 VNZLQLYBRIOLFZ-UHFFFAOYSA-N 0.000 description 7
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 7
150000001408 amides Chemical class 0.000 description 7
239000000377 silicon dioxide Substances 0.000 description 7
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
150000001412 amines Chemical class 0.000 description 6
230000000949 anxiolytic effect Effects 0.000 description 6
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
229910000027 potassium carbonate Inorganic materials 0.000 description 6
239000000843 powder Substances 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
QVHJQCGUWFKTSE-RXMQYKEDSA-N (2r)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound OC(=O)[C@@H](C)NC(=O)OC(C)(C)C QVHJQCGUWFKTSE-RXMQYKEDSA-N 0.000 description 5
102100022738 5-hydroxytryptamine receptor 1A Human genes 0.000 description 5
101710138638 5-hydroxytryptamine receptor 1A Proteins 0.000 description 5
101150049660 DRD2 gene Proteins 0.000 description 5
239000004480 active ingredient Substances 0.000 description 5
239000010410 layer Substances 0.000 description 5
239000012074 organic phase Substances 0.000 description 5
235000015320 potassium carbonate Nutrition 0.000 description 5
238000003756 stirring Methods 0.000 description 5
JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 4
208000019901 Anxiety disease Diseases 0.000 description 4
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
230000036506 anxiety Effects 0.000 description 4
239000012267 brine Substances 0.000 description 4
QWCRAEMEVRGPNT-UHFFFAOYSA-N buspirone Chemical compound C1C(=O)N(CCCCN2CCN(CC2)C=2N=CC=CN=2)C(=O)CC21CCCC2 QWCRAEMEVRGPNT-UHFFFAOYSA-N 0.000 description 4
229960002495 buspirone Drugs 0.000 description 4
239000000969 carrier Substances 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
ZWWWLCMDTZFSOO-UHFFFAOYSA-N diethoxyphosphorylformonitrile Chemical compound CCOP(=O)(C#N)OCC ZWWWLCMDTZFSOO-UHFFFAOYSA-N 0.000 description 4
125000005843 halogen group Chemical group 0.000 description 4
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
239000012071 phase Substances 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
230000008569 process Effects 0.000 description 4
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 4
REHQLKUNRPCYEW-UHFFFAOYSA-N 1-methylcyclohexane-1-carboxylic acid Chemical compound OC(=O)C1(C)CCCCC1 REHQLKUNRPCYEW-UHFFFAOYSA-N 0.000 description 3
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 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
208000028017 Psychotic disease Diseases 0.000 description 3
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
239000005864 Sulphur Substances 0.000 description 3
239000002168 alkylating agent Substances 0.000 description 3
229940100198 alkylating agent Drugs 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
239000002585 base Substances 0.000 description 3
150000004657 carbamic acid derivatives Chemical class 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
238000001035 drying Methods 0.000 description 3
230000032050 esterification Effects 0.000 description 3
238000005886 esterification reaction Methods 0.000 description 3
150000004820 halides Chemical class 0.000 description 3
238000002844 melting Methods 0.000 description 3
239000012044 organic layer Substances 0.000 description 3
238000007911 parenteral administration Methods 0.000 description 3
239000008194 pharmaceutical composition Substances 0.000 description 3
238000000746 purification Methods 0.000 description 3
239000000376 reactant Substances 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
238000010992 reflux Methods 0.000 description 3
239000001632 sodium acetate Substances 0.000 description 3
235000017281 sodium acetate Nutrition 0.000 description 3
229910052938 sodium sulfate Inorganic materials 0.000 description 3
235000011152 sodium sulphate Nutrition 0.000 description 3
OVRJUXJXYNVTLQ-GFCCVEGCSA-N (2r)-1-[4-(2-methoxyphenyl)piperazin-1-yl]propan-2-amine Chemical compound COC1=CC=CC=C1N1CCN(C[C@@H](C)N)CC1 OVRJUXJXYNVTLQ-GFCCVEGCSA-N 0.000 description 2
DEAPGFMNLIPWSI-NVJADKKVSA-N (2r)-2-amino-1-[4-(2-methoxyphenyl)piperazin-1-yl]propan-1-one;dihydrochloride Chemical compound Cl.Cl.COC1=CC=CC=C1N1CCN(C(=O)[C@@H](C)N)CC1 DEAPGFMNLIPWSI-NVJADKKVSA-N 0.000 description 2
DDMVHGULHRJOEC-UHFFFAOYSA-N 1-(2-methoxyphenyl)piperazin-1-ium;chloride Chemical compound Cl.COC1=CC=CC=C1N1CCNCC1 DDMVHGULHRJOEC-UHFFFAOYSA-N 0.000 description 2
238000005160 1H NMR spectroscopy Methods 0.000 description 2
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
ONPJWQSDZCGSQM-UHFFFAOYSA-N 2-phenylprop-2-enoic acid Chemical compound OC(=O)C(=C)C1=CC=CC=C1 ONPJWQSDZCGSQM-UHFFFAOYSA-N 0.000 description 2
ZNZGJSLHXOMREP-UHFFFAOYSA-N 2-piperazin-1-ylpyrimidine;dihydrochloride Chemical compound Cl.Cl.C1CNCCN1C1=NC=CC=N1 ZNZGJSLHXOMREP-UHFFFAOYSA-N 0.000 description 2
IHBVNSPHKMCPST-UHFFFAOYSA-N 3-bromopropanoyl chloride Chemical compound ClC(=O)CCBr IHBVNSPHKMCPST-UHFFFAOYSA-N 0.000 description 2
KZAMQAAMEOXHBU-UHFFFAOYSA-N 5-bromo-2,2-dimethylpentanoic acid Chemical compound OC(=O)C(C)(C)CCCBr KZAMQAAMEOXHBU-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
208000024827 Alzheimer disease Diseases 0.000 description 2
101100424823 Arabidopsis thaliana TDT gene Proteins 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
239000007832 Na2SO4 Substances 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
206010039966 Senile dementia Diseases 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
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 2
150000001298 alcohols Chemical class 0.000 description 2
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ZZTDDUJGFWOPBB-CQSZACIVSA-N tert-butyl n-[(2r)-1-[4-(2-methoxyphenyl)piperazin-1-yl]-1-oxopropan-2-yl]carbamate Chemical compound COC1=CC=CC=C1N1CCN(C(=O)[C@@H](C)NC(=O)OC(C)(C)C)CC1 ZZTDDUJGFWOPBB-CQSZACIVSA-N 0.000 description 1
DDPWVABNMBRBFI-UHFFFAOYSA-N tert-butylhydrazine;hydron;chloride Chemical compound Cl.CC(C)(C)NN DDPWVABNMBRBFI-UHFFFAOYSA-N 0.000 description 1
150000003509 tertiary alcohols Chemical class 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
CFOAUYCPAUGDFF-UHFFFAOYSA-N tosmic Chemical compound CC1=CC=C(S(=O)(=O)C[N+]#[C-])C=C1 CFOAUYCPAUGDFF-UHFFFAOYSA-N 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
DBODNPMIIRVQGW-UHFFFAOYSA-N trihydrate;dihydrochloride Chemical compound O.O.O.Cl.Cl DBODNPMIIRVQGW-UHFFFAOYSA-N 0.000 description 1
238000001665 trituration Methods 0.000 description 1
229950011472 umespirone Drugs 0.000 description 1
150000003672 ureas Chemical class 0.000 description 1
239000001993 wax 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
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/145—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- 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
- A61P25/20—Hypnotics; Sedatives
- 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
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
- 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
- C07D295/084—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 attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—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 attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
- 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
- C07D295/12—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 or doubly bound nitrogen atoms
- C07D295/125—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 or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/13—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 or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D295/145—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/15—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Life Sciences & Earth Sciences (AREA)
Neurology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
Anesthesiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Pyridine Compounds (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

PH40415A 1989-04-22 1990-04-24 Tertiary alkyl functionalized piperazine derivatives PH26582A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB898909209A GB8909209D0 (en)	1989-04-22	1989-04-22	Piperazine derivatives
US07/428,148 US4988814A (en)	1989-04-22	1989-10-27	Tertiary alkyl functionalized piperazine derivatives

Publications (1)

Publication Number	Publication Date
PH26582A true PH26582A (en)	1992-08-19

Family

ID=26295262

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
PH40415A PH26582A (en)	1989-04-22	1990-04-24	Tertiary alkyl functionalized piperazine derivatives

Country Status (16)

Country	Link
EP (2)	EP0955296A3 (fr)
JP (1)	JP3054677B2 (fr)
AT (1)	ATE187718T1 (fr)
CA (1)	CA2015033C (fr)
DE (1)	DE69033393T2 (fr)
DK (1)	DK0395313T3 (fr)
ES (1)	ES2140374T3 (fr)
FI (1)	FI93832C (fr)
GB (1)	GB2230780B (fr)
GR (1)	GR3032634T3 (fr)
HU (1)	HU221315B1 (fr)
IE (1)	IE64038B1 (fr)
IL (1)	IL94160A (fr)
NZ (1)	NZ233398A (fr)
PH (1)	PH26582A (fr)
PT (1)	PT93824B (fr)

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NZ240863A (en) *	1991-09-11	1995-04-27	Mcneilab Inc	Substituted 4-aryl piperidine and 4-aryl piperazine derivatives, preparation and pharmaceutical compositions thereof
GB9125900D0 (en) *	1991-12-05	1992-02-05	Wyeth John & Brother Ltd	Piperazine derivatives
GB9200293D0 (en) *	1992-01-08	1992-02-26	Wyeth John & Brother Ltd	Piperazine derivatives
FR2692894B1 (fr) *	1992-06-24	1994-10-14	Irceba	Aryl-1-(o-alcoxy-phényl-4-pipérazinyl-1)-2, 3- ou 4-alcanols, leur procédé de préparation et leur utilisation pour la préparation de médicaments.
US5321031A (en) *	1992-09-23	1994-06-14	Schering Corporation	1,2-disubstituted ethyl amides as inhibitors of ACAT
GB9221931D0 (en) *	1992-10-17	1992-12-02	Wyeth John & Brother Ltd	Piperazine derivatives
GB9223153D0 (en) *	1992-11-05	1992-12-16	Wyeth John & Brother Ltd	Piperazine derivatives
GB9300195D0 (en) *	1993-01-06	1993-03-03	Wyeth John & Brother Ltd	Piperazine derivatives
GB9303968D0 (en) *	1993-02-26	1993-04-14	Wyeth John & Brother Ltd	5-ht1a ligands
IL110857A0 (en) *	1993-09-09	1994-11-28	Lilly Co Eli	Cessation of tobacco use
GB9525239D0 (en) *	1995-12-09	1996-02-07	American Home Prod	Medical treatment
US5990114A (en) *	1996-02-28	1999-11-23	Recordati, S.A., Chemical And Pharmaceutical Company	Use of 5-HT1A receptor antagonists for the treatment of urinary incontinence
JP3845452B2 (ja)	1996-04-05	2006-11-15	ソシエテ・ド・コンセイユ・ド・ルシエルシエ・エ・ダアツプリカーシヨン・シヤンテイフイツク・（エス．セー．エール．アー．エス）	α１―交感神経受容体拮抗薬
IL125658A0 (en) *	1997-08-18	1999-04-11	Hoffmann La Roche	Ccr-3 receptor antagonists
CN1312802A (zh) *	1998-06-15	2001-09-12	美国家用产品公司	作为5－羟色胺能药物的环烷基取代的芳基哌嗪、哌啶和四氢吡啶
GB9817197D0 (en) *	1998-08-07	1998-10-07	Lilly Co Eli	Pharmaceutical compounds
US6831084B1 (en)	1999-11-12	2004-12-14	Wyeth	Branched adamantyl and noradamantyl aryl- and aralkylpiperazines with serotonin 5-HT1A activity
JP2003517468A (ja)	1999-11-12	2003-05-27	ワイス	セロトニン５−ｈｔ１ａ活性を有する分枝アダマンチルおよびノルアダマチルアリール−およびアラルキルピペラジン
ES2275853T3 (es) *	2001-02-16	2007-06-16	Aventis Pharmaceuticals Inc.	Derivados heterociclicos de urea y su uso como ligandos de receptores de dopamina d3.
WO2002085871A2 (fr)	2001-04-04	2002-10-31	Wyeth	Agents serotonergiques presentant des effets in vivo a action prolongee
US7067518B2 (en)	2002-09-05	2006-06-27	Wyeth	Pyridinyl-methyl-ethyl cyclohexanecarboxamides as serotonergic agents
US7179813B2 (en) *	2003-06-11	2007-02-20	Wyeth	Bicyclic indolyl derivatives and methods for their use as serotonergic agents
ATE537169T1 (de)	2005-08-15	2011-12-15	Hoffmann La Roche	Piperidin- und piperazinderivate als p2x3- antagonisten
AU2008251259B2 (en) *	2007-05-14	2013-02-14	Sk Biopharmaceuticals Co., Ltd.	Novel carbamoyloxy arylalkanoyl arylpiperazine compound, pharmaceutical compositions comprising the compound and method for treating pain, anxiety and depression by administering the compound
DK2906221T3 (da) *	2012-10-11	2019-07-22	Southern Res Inst	Urinstof og amidderivater af aminoalkylpiperaziner og anvendelse deraf

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US3272819A (en) *	1963-12-16	1966-09-13	Ciba Geigy Corp	Amino esters of spiro (cyclopropan-1, 9'-thioxanthene)-2-carboxylic acid
JPS5931508B2 (ja) *	1975-11-13	1984-08-02	ウェルファイド株式会社	ジヒドロベンゾフランユウドウタイノセイホウ
JPS6019305B2 (ja) *	1976-07-02	1985-05-15	ウェルファイド株式会社	ジヒドロベンゾフラン誘導体
DE2727469A1 (de) *	1977-06-18	1978-12-21	Hoechst Ag	Neue hexahydropyrimidine, verfahren zu ihrer herstellung und arzneimittel, die diese verbindungen enthalten
US4202898A (en) *	1978-06-05	1980-05-13	Synthelabo	Method of treating anxiety and depression
JPS5513209A (en) *	1978-07-11	1980-01-30	Synthelabo	Antidepressive made of piperazine derivative
FR2432516A1 (fr) *	1978-08-01	1980-02-29	Synthelabo	Derives de phenyl-4 piperazino-ethanol et leur application en therapeutique
AU532411B2 (en) *	1979-03-01	1983-09-29	Duphar International Research B.V.	Phenyl piperazine derivatives
NL8005133A (nl) *	1980-09-12	1982-04-01	Duphar Int Res	Fenylpiperazinederivaten met antiagressieve werking.
US4605655A (en) *	1984-03-06	1986-08-12	Bristol-Myers Company	Antipsychotic 1-fluorophenylbutyl-4-(2-pyrimidinyl)piperazine derivatives
AR242678A1 (es) *	1986-03-05	1993-04-30	Gonzalez Jorge Alberto	Mejoras en instrumentos musicales de cuerda de arco.
US4797489A (en) *	1987-12-02	1989-01-10	American Home Products Corp.	Adamantyl- and fluorenyl-arylpiperazines and -arylpiperidines

1990
- 1990-04-20 NZ NZ233398A patent/NZ233398A/en unknown
- 1990-04-20 DE DE69033393T patent/DE69033393T2/de not_active Expired - Fee Related
- 1990-04-20 ES ES90304251T patent/ES2140374T3/es not_active Expired - Lifetime
- 1990-04-20 HU HU503/90A patent/HU221315B1/hu not_active IP Right Cessation
- 1990-04-20 PT PT93824A patent/PT93824B/pt active IP Right Grant
- 1990-04-20 AT AT90304251T patent/ATE187718T1/de not_active IP Right Cessation
- 1990-04-20 EP EP99108070A patent/EP0955296A3/fr not_active Withdrawn
- 1990-04-20 DK DK90304251T patent/DK0395313T3/da active
- 1990-04-20 EP EP90304251A patent/EP0395313B1/fr not_active Expired - Lifetime
- 1990-04-20 GB GB9008924A patent/GB2230780B/en not_active Expired - Fee Related
- 1990-04-20 IE IE141790A patent/IE64038B1/en not_active IP Right Cessation
- 1990-04-20 CA CA002015033A patent/CA2015033C/fr not_active Expired - Fee Related
- 1990-04-20 FI FI901982A patent/FI93832C/fi not_active IP Right Cessation
- 1990-04-21 JP JP2106300A patent/JP3054677B2/ja not_active Expired - Fee Related
- 1990-04-22 IL IL9416090A patent/IL94160A/en not_active IP Right Cessation
- 1990-04-24 PH PH40415A patent/PH26582A/en unknown
2000
- 2000-02-10 GR GR20000400332T patent/GR3032634T3/el not_active IP Right Cessation

Also Published As

Publication number	Publication date
HU221315B1 (en)	2002-09-28
IL94160A0 (en)	1991-01-31
HUT54667A (en)	1991-03-28
GR3032634T3 (en)	2000-05-31
ES2140374T3 (es)	2000-03-01
IE64038B1 (en)	1995-06-28
GB9008924D0 (en)	1990-06-20
EP0955296A2 (fr)	1999-11-10
CA2015033A1 (fr)	1990-10-22
JPH0320263A (ja)	1991-01-29
IE901417L (en)	1990-10-22
DK0395313T3 (da)	2000-06-19
CA2015033C (fr)	2000-06-06
FI93832C (fi)	1995-06-12
AU5377890A (en)	1990-10-25
AU619677B2 (en)	1992-01-30
EP0955296A3 (fr)	2000-01-19
GB2230780A (en)	1990-10-31
FI93832B (fi)	1995-02-28
DE69033393T2 (de)	2000-05-25
JP3054677B2 (ja)	2000-06-19
ATE187718T1 (de)	2000-01-15
HU902503D0 (en)	1990-08-28
PT93824A (pt)	1990-11-20
DE69033393D1 (de)	2000-01-20
EP0395313B1 (fr)	1999-12-15
EP0395313A3 (fr)	1991-05-08
PT93824B (pt)	1996-09-30
FI901982A0 (fi)	1990-04-20
IL94160A (en)	1994-06-24
NZ233398A (en)	1991-12-23
EP0395313A2 (fr)	1990-10-31
GB2230780B (en)	1992-10-21

Publication	Publication Date	Title
US4988814A (en)	1991-01-29	Tertiary alkyl functionalized piperazine derivatives
CA2015033C (fr)	2000-06-06	Derives piperazine a fonction alkyl tertiaire
RU2193561C2 (ru)	2002-11-27	Производные пиперазина, способ их получения, фармацевтическая композиция, промежуточное соединение
KR0173310B1 (ko)	1999-02-01	피페라진 유도체
EP1656351B1 (fr)	2007-12-19	Procede de preparation de derives de 4-aryl-nicotinamide
AU710835B2 (en)	1999-09-30	Novel substituted (2-(1-piperazinyl)ethoxy)methyl compounds
EP0737678B1 (fr)	2002-06-19	Dérivés de 4-indolylpipérazinyle
EP0689534B1 (fr)	2002-10-02	Derives amides en tant que ligands 5-ht 1a?
US5519025A (en)	1996-05-21	4-indolylpiperazinyl derivatives
US5364849A (en)	1994-11-15	1-[3 or 4-[1-[4-piperazinyl]]-2 arylpropionyl or butryl]-heterocyclic derivatives
HU202508B (en)	1991-03-28	Process for producing new 1,4-disubstituted piperazine derivatives and pharmaceutical compositions containing them as active components
GB2352240A (en)	2001-01-24	Novel sulphonamides useful in treating CNS disorders
CA2420935A1 (fr)	2002-03-07	N-(3,5-dichloro-2-methoxyphenyl)-4-methoxy-3-piperazin-1-yl-benzenesulfonamide
US2621182A (en)	1952-12-09	Office
CS241064B2 (en)	1986-03-13	Method of n-substituted nicotinamide's 1-oxide and its salts production
AU642043B2 (en)	1993-10-07	Piperazine derivatives
US5610295A (en)	1997-03-11	4-amino-2-(hetero)aryl-butanamides useful as 5-HT1A -antagonists
HK1010102B (en)	2002-11-15	4-indolylpiperazinyl derivatives