NO300685B1 - Fremgangsmåte for fremstilling av arylpiperazinyl-heterocykliske forbindelser - Google Patents

Fremgangsmåte for fremstilling av arylpiperazinyl-heterocykliske forbindelser Download PDF

Info

Publication number: NO300685B1
Authority: NO; Norway
Prior art keywords: neutralizing agent; compound; approx; formula; piperazine
Prior art date: 1992-08-26

Application number

NO931656A

Other languages

English (en)

Norwegian (no)

Other versions

NO931656D0 (no

NO931656L (no

Inventor

Frank R Busch

Paul Bowles

Douglas J M Allen

Sabeto A Diroma

Dennis M Godek

Original Assignee

Pfizer

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.)

1992-08-26

Filing date

1993-05-06

Publication date

1997-07-07

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=25468285&utm_source=***_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=NO300685(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1993-05-06 Application filed by Pfizer filed Critical Pfizer

1993-05-06 Publication of NO931656D0 publication Critical patent/NO931656D0/no

1994-02-28 Publication of NO931656L publication Critical patent/NO931656L/no

1997-07-07 Publication of NO300685B1 publication Critical patent/NO300685B1/no

Links

238000000034 method Methods 0.000 title claims description 32
238000002360 preparation method Methods 0.000 title description 5
150000001875 compounds Chemical class 0.000 claims abstract description 33
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims abstract description 20
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 18
239000002253 acid Substances 0.000 claims abstract description 14
150000001350 alkyl halides Chemical class 0.000 claims abstract description 11
239000000203 mixture Substances 0.000 claims abstract description 11
238000005859 coupling reaction Methods 0.000 claims abstract description 9
150000003839 salts Chemical class 0.000 claims abstract description 9
238000010168 coupling process Methods 0.000 claims abstract description 8
230000008878 coupling Effects 0.000 claims abstract description 7
239000003153 chemical reaction reagent Substances 0.000 claims abstract description 4
230000000694 effects Effects 0.000 claims abstract description 3
238000010438 heat treatment Methods 0.000 claims abstract description 3
-1 6-hydroxy-8-quinolyl Chemical group 0.000 claims description 35
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical group [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 18
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
239000003795 chemical substances by application Substances 0.000 claims description 14
230000003472 neutralizing effect Effects 0.000 claims description 14
229910052801 chlorine Inorganic materials 0.000 claims description 12
239000000460 chlorine Substances 0.000 claims description 12
229910052731 fluorine Inorganic materials 0.000 claims description 12
238000006243 chemical reaction Methods 0.000 claims description 11
238000010992 reflux Methods 0.000 claims description 11
239000000758 substrate Substances 0.000 claims description 11
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 10
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 10
239000011737 fluorine Substances 0.000 claims description 10
229910000029 sodium carbonate Inorganic materials 0.000 claims description 9
125000001424 substituent group Chemical group 0.000 claims description 8
238000001914 filtration Methods 0.000 claims description 6
125000004095 oxindolyl group Chemical group N1(C(CC2=CC=CC=C12)=O)* 0.000 claims description 6
125000001624 naphthyl group Chemical group 0.000 claims description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims description 4
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
229910052794 bromium Inorganic materials 0.000 claims description 4
125000004093 cyano group Chemical group *C#N 0.000 claims description 4
125000004122 cyclic group Chemical group 0.000 claims description 4
125000001153 fluoro group Chemical group F* 0.000 claims description 4
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 4
125000001041 indolyl group Chemical group 0.000 claims description 4
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
150000004885 piperazines Chemical class 0.000 claims description 4
125000005493 quinolyl group Chemical group 0.000 claims description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
229910052784 alkaline earth metal Inorganic materials 0.000 claims description 3
MVWVFYHBGMAFLY-UHFFFAOYSA-N ziprasidone Chemical compound C1=CC=C2C(N3CCN(CC3)CCC3=CC=4CC(=O)NC=4C=C3Cl)=NSC2=C1 MVWVFYHBGMAFLY-UHFFFAOYSA-N 0.000 claims description 3
ZCBZSCBNOOIHFP-UHFFFAOYSA-N ziprasidone hydrochloride hydrate Chemical compound [H+].O.[Cl-].C1=CC=C2C(N3CCN(CC3)CCC3=CC=4CC(=O)NC=4C=C3Cl)=NSC2=C1 ZCBZSCBNOOIHFP-UHFFFAOYSA-N 0.000 claims description 3
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 2
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 2
125000005874 benzothiadiazolyl group Chemical group 0.000 claims description 2
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 2
125000005956 isoquinolyl group Chemical group 0.000 claims description 2
125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 2
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 2
125000003003 spiro group Chemical group 0.000 claims description 2
150000003512 tertiary amines Chemical class 0.000 claims description 2
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims 1
229910000288 alkali metal carbonate Inorganic materials 0.000 claims 1
150000008041 alkali metal carbonates Chemical class 0.000 claims 1
238000001816 cooling Methods 0.000 claims 1
150000004678 hydrides Chemical class 0.000 claims 1
231100000241 scar Toxicity 0.000 claims 1
150000008648 triflates Chemical class 0.000 claims 1
238000004519 manufacturing process Methods 0.000 abstract description 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 21
239000000047 product Substances 0.000 description 19
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
238000004128 high performance liquid chromatography Methods 0.000 description 8
239000000243 solution Substances 0.000 description 8
208000028017 Psychotic disease Diseases 0.000 description 5
239000004480 active ingredient Substances 0.000 description 5
239000012458 free base Substances 0.000 description 5
238000004458 analytical method Methods 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
238000001953 recrystallisation Methods 0.000 description 4
238000006467 substitution reaction Methods 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
239000012065 filter cake Substances 0.000 description 3
238000001990 intravenous administration Methods 0.000 description 3
239000000463 material Substances 0.000 description 3
239000002002 slurry Substances 0.000 description 3
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
DOQLJTKEUIJSKK-UHFFFAOYSA-N 3-piperazin-1-yl-1,2-benzothiazole;hydrochloride Chemical compound Cl.C1CNCCN1C1=NSC2=CC=CC=C12 DOQLJTKEUIJSKK-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
229920002261 Corn starch Polymers 0.000 description 2
RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
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 2
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
238000005481 NMR spectroscopy Methods 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
240000004922 Vigna radiata Species 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
150000005303 alkyl halide derivatives Chemical class 0.000 description 2
239000007900 aqueous suspension Substances 0.000 description 2
239000002585 base Substances 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
239000006227 byproduct Substances 0.000 description 2
239000002775 capsule Substances 0.000 description 2
239000008120 corn starch Substances 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
238000001035 drying Methods 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
238000007918 intramuscular administration Methods 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
239000008101 lactose Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
230000014759 maintenance of location Effects 0.000 description 2
238000002844 melting Methods 0.000 description 2
230000008018 melting Effects 0.000 description 2
230000000701 neuroleptic effect Effects 0.000 description 2
239000000825 pharmaceutical preparation Substances 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
239000000126 substance Substances 0.000 description 2
208000024891 symptom Diseases 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
ZDFQBFVFCPABKQ-UHFFFAOYSA-N 3-piperazin-1-yl-1,2-benzoxazole Chemical class C1CNCCN1C1=NOC2=CC=CC=C12 ZDFQBFVFCPABKQ-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
NJMAWIQVAJTHGR-UHFFFAOYSA-N 6-chloro-1-(2-chloroethyl)-3h-indol-2-one Chemical compound C1=C(Cl)C=C2N(CCCl)C(=O)CC2=C1 NJMAWIQVAJTHGR-UHFFFAOYSA-N 0.000 description 1
208000019901 Anxiety disease Diseases 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
206010014557 Emotional poverty Diseases 0.000 description 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
241000282412 Homo Species 0.000 description 1
KRDOFMHJLWKXIU-UHFFFAOYSA-N ID11614 Chemical compound C1CNCCN1C1=NSC2=CC=CC=C12 KRDOFMHJLWKXIU-UHFFFAOYSA-N 0.000 description 1
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
206010041243 Social avoidant behaviour Diseases 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
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 1
230000016571 aggressive behavior Effects 0.000 description 1
238000013019 agitation Methods 0.000 description 1
239000003513 alkali Substances 0.000 description 1
125000000217 alkyl group Chemical group 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
230000036506 anxiety Effects 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
229940092714 benzenesulfonic acid Drugs 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
239000000969 carrier Substances 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
235000013985 cinnamic acid Nutrition 0.000 description 1
229930016911 cinnamic acid Natural products 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
239000012043 crude product Substances 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
230000008014 freezing Effects 0.000 description 1
238000007710 freezing Methods 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
235000011087 fumaric acid Nutrition 0.000 description 1
239000000174 gluconic acid Substances 0.000 description 1
235000012208 gluconic acid Nutrition 0.000 description 1
150000002391 heterocyclic compounds Chemical class 0.000 description 1
DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
229940071870 hydroiodic acid Drugs 0.000 description 1
238000002955 isolation Methods 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
150000004682 monohydrates Chemical class 0.000 description 1
LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
239000003176 neuroleptic agent Substances 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
238000000746 purification Methods 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
230000004044 response Effects 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
230000000698 schizophrenic effect Effects 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
235000009518 sodium iodide Nutrition 0.000 description 1
239000002904 solvent Substances 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
229940066771 systemic antihistamines piperazine derivative Drugs 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
238000005292 vacuum distillation Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
- 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
- A61P25/20—Hypnotics; Sedatives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Public Health (AREA)
Neurosurgery (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Neurology (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Biomedical Technology (AREA)
Veterinary Medicine (AREA)
Psychiatry (AREA)
Anesthesiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Indole Compounds (AREA)
Thiazole And Isothizaole Compounds (AREA)
Quinoline Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Cephalosporin Compounds (AREA)
Lubricants (AREA)
Management, Administration, Business Operations System, And Electronic Commerce (AREA)
Eye Examination Apparatus (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

NO931656A 1992-08-26 1993-05-06 Fremgangsmåte for fremstilling av arylpiperazinyl-heterocykliske forbindelser NO300685B1 (no)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US07/936,179 US5206366A (en)	1992-08-26	1992-08-26	Process for preparing aryl piperazinyl-heterocyclic compounds

Publications (3)

Publication Number	Publication Date
NO931656D0 NO931656D0 (no)	1993-05-06
NO931656L NO931656L (no)	1994-02-28
NO300685B1 true NO300685B1 (no)	1997-07-07

Family

ID=25468285

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO931656A NO300685B1 (no)	1992-08-26	1993-05-06	Fremgangsmåte for fremstilling av arylpiperazinyl-heterocykliske forbindelser

Country Status (27)

Country	Link
US (1)	US5206366A (xx)
EP (2)	EP1029861B1 (xx)
JP (1)	JP2742370B2 (xx)
KR (1)	KR0123441B1 (xx)
CN (1)	CN1033089C (xx)
AT (2)	ATE206422T1 (xx)
AU (1)	AU642836B1 (xx)
BR (1)	BR9302065A (xx)
CZ (1)	CZ281893B6 (xx)
DE (2)	DE69333597T2 (xx)
DK (2)	DK1029861T3 (xx)
EG (1)	EG20214A (xx)
ES (2)	ES2225015T3 (xx)
FI (1)	FI111641B (xx)
HU (1)	HU223312B1 (xx)
IL (1)	IL105622A (xx)
MX (1)	MX9302813A (xx)
MY (1)	MY109731A (xx)
NO (1)	NO300685B1 (xx)
NZ (1)	NZ247539A (xx)
PL (1)	PL173840B1 (xx)
PT (2)	PT1029861E (xx)
RU (1)	RU2061695C1 (xx)
SI (1)	SI9300287A (xx)
SK (1)	SK280584B6 (xx)
YU (1)	YU48964B (xx)
ZA (1)	ZA936225B (xx)

Families Citing this family (46)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5338846A (en) *	1992-08-26	1994-08-16	Pfizer Inc.	Process for preparing aryl piperazinyl-heterocyclic compounds with a piperazine salt
US5206366A (en) *	1992-08-26	1993-04-27	Pfizer Inc.	Process for preparing aryl piperazinyl-heterocyclic compounds
US5359068A (en) *	1993-06-28	1994-10-25	Pfizer Inc.	Processes and intermediates for the preparation of 5-[2-(4-(benzoisothiazol-3-yl)-piperazin-1-yl)ethyl]-6-chloro-1,3-dihydro-indol-2-one
HUP9802492A3 (en) *	1995-06-06	1999-10-28	Hoechst Marion Roussel Inc Cin	Benzisoxazole and indazole derivatives as antipsychotic agents, process for their preparation and pharmaceutical compositions containing the same
TW491847B (en) *	1996-05-07	2002-06-21	Pfizer	Mesylate dihydrate salts of 5-(2-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)-ethyl)-6-chloro-1,3-dihydro-2h-indol-2-one
KR100333214B1 (ko) *	1996-05-07	2002-06-20	디. 제이. 우드, 스피겔 알렌 제이	5-(2-(4-(1,2-벤즈이소티아졸-3-일)-1-피페라지닐)에틸)-6-클로로-1,3-디하이드로-2(1에이치)인돌-2-온(지프라시돈)의메실레이트트리하이드레이트염,이의제조방법및도파민디2길항물질로서의이의용도
US5945421A (en) *	1997-08-11	1999-08-31	Warner-Lambert Company	Dopamine D4 receptor antagonists
US6040448A (en) *	1997-10-24	2000-03-21	Neurogen Corporation	Certain 1-(2-naphthyl) and 1-(2-azanaphthyl)-4-(1-phenylmethyl) piperazines, dopamine receptor subtype specific ligands
IL127497A (en) *	1997-12-18	2002-07-25	Pfizer Prod Inc	Medicinal products containing piperazinyl-heterocyclic compounds for the treatment of psychiatric disorders
KR20010041625A (ko) *	1998-03-06	2001-05-25	아스트라제네카 악티에볼라그	신규 용도
US6150366A (en) *	1998-06-15	2000-11-21	Pfizer Inc.	Ziprasidone formulations
US6660858B2 (en)	2001-03-28	2003-12-09	Lion Bioscience Ag	2-aminobenzoxazole derivatives and combinatorial libraries thereof
UY27668A1 (es)	2002-02-20	2003-10-31	Pfizer Prod Inc	Composición de ziprasidona y controles sintéticos
US20040048876A1 (en) *	2002-02-20	2004-03-11	Pfizer Inc.	Ziprasidone composition and synthetic controls
KR20050057404A (ko) *	2002-09-17	2005-06-16	워너-램버트 캄파니 엘엘씨	정신분열증 치료용 헤테로환 치환된 피페라진
ES2297200T3 (es) *	2002-10-24	2008-05-01	Pfizer Products Inc.	Derivados de acilo de 5-(2-(4-(1,2 bencisotiazol-3-il)-1-piperazinil)etil)-6-cloro-1,3-dihidro-2h-indol-2-ona que presentan actividad neuroleptica.
BR0316108A (pt) *	2002-11-08	2005-09-27	Warner Lambert Co	Derivados de fenilalquil e piridilalquil piperazina e composição farmacêutica compreendendo os mesmos
WO2004050655A1 (en) *	2002-12-04	2004-06-17	Dr. Reddy's Laboratories Limited	Polymorphic forms of ziprasidone and its hydrochloride
US7488729B2 (en)	2002-12-04	2009-02-10	Dr. Reddy's Laboratories Limited	Polymorphic forms of ziprasidone and its hydrochloride salt and process for preparation thereof
CN1255105C (zh) *	2002-12-17	2006-05-10	上海医药工业研究院	齐拉西酮及其盐的水溶性包合物及其制备方法
US20050143396A1 (en) *	2003-04-11	2005-06-30	Hertero Drugs Limited	Novel crystalline forms of ziprasidone hydrochloride
EP1530570A2 (en) *	2003-06-03	2005-05-18	Teva Pharmaceutical Industries Limited	CRISTALLINE ZIPRASIDONE HCl AND PROCESSES FOR PREPARATION THEREOF
US20050049295A1 (en) *	2003-06-12	2005-03-03	Dr. Reddy's Laboratories Limited	Process for the preparation of 5-(2-(4-(1,2-benzisothiazol-3-yl)-1piperazinyl) ethyl)-6-chloro-1, 3-dihydro-2h-indol-2-one hydrochloride (ziprasidone hydrochloride) and its intermediate
US7160888B2 (en) *	2003-08-22	2007-01-09	Warner Lambert Company Llc	[1,8]naphthyridin-2-ones and related compounds for the treatment of schizophrenia
US7667037B2 (en)	2003-10-24	2010-02-23	Teva Pharmaceutical Industries Ltd.	Processes for preparation of ziprasidone
CA2550485A1 (en) *	2003-12-18	2005-07-07	Teva Pharmaceutical Industries Ltd.	Polymorphic form b2 of ziprasidone base
WO2005085240A2 (en) *	2004-02-27	2005-09-15	Ranbaxy Laboratories Limited	Process for the preparation of ziprasidone
ITMI20040944A1 (it) *	2004-05-11	2004-08-11	Dinamite Dipharma S P A In For	Polimorfo di ziprasidone cloridrato e procedimento per la sua preparazione
CA2467538C (en) *	2004-05-14	2010-08-24	Apotex Pharmachem Inc.	New amorphous ziprasidone hydrochloride (5-[2-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]ethyl]-6-chloro-1,3-dihydro-2h-indol-2-one hydrochloride) and processes to produce the same
CA2471219A1 (en) *	2004-06-14	2005-12-14	Apotex Pharmachem Inc.	Improved preparation of an anhydrate form of 5-[2-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]ethyl]-6-chloro-1,3-dihydro-2h-indol-2-one hydrochloride (ziprasidone hydrochloride)
US7728136B2 (en)	2004-06-18	2010-06-01	Lupin Limited	Method for the preparation of aryl piperazinyl-heterocyclic compounds
WO2006026426A2 (en) *	2004-08-27	2006-03-09	University Of Kentucky Research Foundation	Amyloid peptide inactivating enzyme to treat alzheimer’s disease peripherally
ES2250001B1 (es) *	2004-09-29	2007-06-01	Medichem, S.A.	Proceso para la purificacion de ziprasidona.
ES2250000B1 (es) *	2004-09-29	2007-06-01	Medichem, S.A.	Procedimiento para la preparacion de ziprasidona.
US7777037B2 (en) *	2004-10-27	2010-08-17	Dr. Reddy's Laboratories Limited	Ziprasidone process
WO2006086779A1 (en) *	2005-02-11	2006-08-17	Teva Pharmaceutical Industries Ltd.	Amorphous ziprasidone mesylate
WO2006099452A1 (en) *	2005-03-14	2006-09-21	Teva Pharmaceutical Industries Ltd.	Anhydrous ziprasidone mesylate and a process for its preparation
CA2599391A1 (en) *	2005-03-14	2006-09-21	Teva Pharmaceutical Industries Ltd.	Crystalline forms of ziprasidone mesylate
EA200701856A1 (ru) *	2005-04-01	2008-02-28	Уорнер-Ламберт Компани Ллс	Тетрагидропиридоазепин-8-оны и родственные соединения для лечения шизофрении
HU230479B1 (hu) *	2006-05-02	2016-07-28	Richter Gedeon Nyrt.	Eljárás 5-{2-[4-(1,2-benzizotiazol-3-il)-1-piperazinil]-etil}-6-klór-1,3-dihidro-2H-indol-2-on (Ziprasidon) előállítására
HUP0600868A3 (en) *	2006-11-24	2009-03-30	Richter Gedeon Nyrt	5-{2-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]ethyl}-6-chloro-1,3-dihydro-2h-indol-2-one hydrogen bromide polimorphs and process for their preparation
WO2009116085A2 (en) *	2008-03-11	2009-09-24	Alkem Laboratories Ltd.	An improved process for the preparation of ziprasidone
WO2011143430A1 (en)	2010-05-12	2011-11-17	Abbott Laboratories	Indazole inhibitors of kinase
PL391810A1 (pl)	2010-07-14	2012-01-16	Zakłady Farmaceutyczne POLPHARMA Spółka Akcyjna	Nowe sole ziprasidonu oraz sposoby ich otrzymywania
WO2012020424A1 (en)	2010-08-12	2012-02-16	Arch Pharmalabs Limited	A short process for the preparation of ziprasidone and intermediates thereof
SI23610A (sl)	2011-01-13	2012-07-31	Diagen@d@o@o	Nove adicijske soli ziprasidona postopek za njihovo pripravo in njihova uporaba v terapiji

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4610988A (en) *	1982-04-09	1986-09-09	Hoechst-Roussel Pharmaceuticals Inc.	1-[3-(6-fluoro-1,2-benzisoxazol-3-yl)propyl]-4-(substituted)piperazines useful for alleviating pain
FR2536749A1 (fr) *	1982-11-25	1984-06-01	Cerm Cent Europ Rech Mauvernay	(amino-2 ethyl)-6 benzoxazolinones substituees, leur preparation et leurs applications en therapeutique
MX173362B (es) *	1987-03-02	1994-02-23	Pfizer	Compuestos de piperazinil heterociclicos y procedimiento para su preparacion
US4831031A (en) *	1988-01-22	1989-05-16	Pfizer Inc.	Aryl piperazinyl-(C2 or C4) alkylene heterocyclic compounds having neuroleptic activity
US4883795A (en) *	1988-01-22	1989-11-28	Pfizer Inc.	Piperazinyl-heterocyclic compounds
US5206366A (en) *	1992-08-26	1993-04-27	Pfizer Inc.	Process for preparing aryl piperazinyl-heterocyclic compounds
US5312925A (en) *	1992-09-01	1994-05-17	Pfizer Inc.	Monohydrate of 5-(2-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)-ethyl)-6-chloro-1,3-dihydro-2H-indol-2-one-hydrochloride

1992
- 1992-08-26 US US07/936,179 patent/US5206366A/en not_active Expired - Lifetime
1993
- 1993-05-03 NZ NZ247539A patent/NZ247539A/xx not_active IP Right Cessation
- 1993-05-04 FI FI932012A patent/FI111641B/fi active Protection Beyond IP Right Term
- 1993-05-04 HU HU9301291A patent/HU223312B1/hu not_active IP Right Cessation
- 1993-05-05 AU AU38403/93A patent/AU642836B1/en not_active Ceased
- 1993-05-06 IL IL105622A patent/IL105622A/en not_active IP Right Cessation
- 1993-05-06 NO NO931656A patent/NO300685B1/no unknown
- 1993-05-07 DK DK00201940T patent/DK1029861T3/da active
- 1993-05-07 DE DE69333597T patent/DE69333597T2/de not_active Expired - Lifetime
- 1993-05-07 ES ES00201940T patent/ES2225015T3/es not_active Expired - Lifetime
- 1993-05-07 MY MYPI93000857A patent/MY109731A/en unknown
- 1993-05-07 ES ES93303576T patent/ES2161703T3/es not_active Expired - Lifetime
- 1993-05-07 DE DE69330853T patent/DE69330853T2/de not_active Expired - Fee Related
- 1993-05-07 DK DK93303576T patent/DK0584903T3/da active
- 1993-05-07 EP EP00201940A patent/EP1029861B1/en not_active Expired - Lifetime
- 1993-05-07 PT PT00201940T patent/PT1029861E/pt unknown
- 1993-05-07 PT PT93303576T patent/PT584903E/pt unknown
- 1993-05-07 AT AT93303576T patent/ATE206422T1/de not_active IP Right Cessation
- 1993-05-07 AT AT00201940T patent/ATE273976T1/de active
- 1993-05-07 EP EP93303576A patent/EP0584903B1/en not_active Expired - Lifetime
- 1993-05-12 CZ CZ93877A patent/CZ281893B6/cs not_active IP Right Cessation
- 1993-05-13 MX MX9302813A patent/MX9302813A/es not_active IP Right Cessation
- 1993-05-13 EG EG27793A patent/EG20214A/xx active
- 1993-05-14 SK SK485-93A patent/SK280584B6/sk not_active IP Right Cessation
- 1993-05-19 PL PL93299002A patent/PL173840B1/pl not_active IP Right Cessation
- 1993-05-26 BR BR9302065A patent/BR9302065A/pt not_active Application Discontinuation
- 1993-05-28 SI SI9300287A patent/SI9300287A/sl not_active IP Right Cessation
- 1993-05-28 RU RU9393028444A patent/RU2061695C1/ru not_active IP Right Cessation
- 1993-06-04 CN CN93106669A patent/CN1033089C/zh not_active Expired - Fee Related
- 1993-07-20 KR KR1019930013678A patent/KR0123441B1/ko not_active IP Right Cessation
- 1993-08-13 JP JP5201542A patent/JP2742370B2/ja not_active Expired - Lifetime
- 1993-08-25 ZA ZA936225A patent/ZA936225B/xx unknown
- 1993-08-25 YU YU56593A patent/YU48964B/sh unknown

Also Published As

Publication number	Publication date
DE69330853T2 (de)	2002-05-02
CN1033089C (zh)	1996-10-23
ZA936225B (en)	1995-02-27
SK280584B6 (sk)	2000-04-10
ATE206422T1 (de)	2001-10-15
CZ281893B6 (cs)	1997-03-12
HUT65750A (en)	1994-07-28
EG20214A (en)	1997-11-30
CN1083061A (zh)	1994-03-02
EP0584903A1 (en)	1994-03-02
ES2225015T3 (es)	2005-03-16
FI932012A (fi)	1994-02-27
EP1029861A1 (en)	2000-08-23
FI932012A0 (fi)	1993-05-04
YU56593A (sh)	1996-07-24
FI111641B (fi)	2003-08-29
DK1029861T3 (da)	2004-11-15
EP1029861B1 (en)	2004-08-18
DE69333597D1 (de)	2004-09-23
CZ87793A3 (en)	1994-04-13
YU48964B (sh)	2003-01-31
BR9302065A (pt)	1994-07-26
HU9301291D0 (en)	1993-07-28
AU642836B1 (en)	1993-10-28
PL299002A1 (en)	1994-03-21
KR940003952A (ko)	1994-03-14
US5206366A (en)	1993-04-27
PT584903E (pt)	2002-02-28
NO931656D0 (no)	1993-05-06
PT1029861E (pt)	2004-11-30
ATE273976T1 (de)	2004-09-15
PL173840B1 (pl)	1998-05-29
MY109731A (en)	1997-05-31
HU223312B1 (hu)	2004-05-28
JP2742370B2 (ja)	1998-04-22
MX9302813A (es)	1994-02-28
ES2161703T3 (es)	2001-12-16
DK0584903T3 (da)	2001-12-03
DE69333597T2 (de)	2005-09-15
SI9300287A (en)	1994-03-31
DE69330853D1 (de)	2001-11-08
JPH06184143A (ja)	1994-07-05
KR0123441B1 (ko)	1997-11-24
EP0584903B1 (en)	2001-10-04
RU2061695C1 (ru)	1996-06-10
SK48593A3 (en)	1994-04-06
NO931656L (no)	1994-02-28
NZ247539A (en)	1995-09-26
IL105622A (en)	1998-06-15
IL105622A0 (en)	1993-09-22

Publication	Publication Date	Title
NO300685B1 (no)	1997-07-07	Fremgangsmåte for fremstilling av arylpiperazinyl-heterocykliske forbindelser
US5338846A (en)	1994-08-16	Process for preparing aryl piperazinyl-heterocyclic compounds with a piperazine salt
TW416953B (en)	2001-01-01	Tricyclic compounds for eliciting a prostaglandin I2 receptor agonistic effect, their production and use
US20090264473A1 (en)	2009-10-22	Novel Crystalline Forms of Antidiabetic Compounds
DK162389B (da)	1991-10-21	Analogifremgangsmaade til fremstilling af 2-oe4-oe(4,4-dialkyl-2,6-piperidindion-1-yl)butylaa-1-piperazinylaapyrimidiner
NO300270B1 (no)	1997-05-05	Monohydrat av 5(2-(4-(1,2-benzisotiazol-3-yl)-1-piperazinyl)-etyl)-6-klor-1,3-dihydro-2H-indol-2-on hydroklorid
JP4776136B2 (ja)	2011-09-21	アミド化合物およびその用途
JP4664673B2 (ja)	2011-04-06	Ｎｏｓ阻害活性を有するアミノベンゾチアゾール化合物
DK162284B (da)	1991-10-07	Analogifremgangsmaade til fremstilling af 2-oe4-oe(4-substituerede-2,6-piperidindion-1-yl)butylaa-1-piperazinylaa-3-cyanopyridiner
CN111548345A (zh)	2020-08-18	一类苯并咪唑类衍生物及其制备方法和应用
NO170582B (no)	1992-07-27	Analogifremgangsmaate for fremstilling av terapeutisk aktive aryl-piperazinyl-alkylenfenyl-heterocykliske forbindelser
DK149947B (da)	1986-11-03	Analogifremgangsmaade til fremstilling af 1,5-diphenylpyrazolin-3-on-forbindelser eller syreadditionssalte deraf
KR20010072775A (ko)	2001-07-31	항당뇨병성 피페라진 유도체, 이들 제제의 제조방법 및이를 함유하는 조성물
EP1927591A1 (en)	2008-06-04	Polymorphic Forms of Deferasirox (ICL670)
JPH01249779A (ja)	1989-10-05	新規の塩基的に置換された５‐ハロゲン‐チエノイソチアゾール‐３‐（２ｈ）‐オン‐１，１‐オキシド、その製造方法及びこの化合物を含有する薬学的調製物
CN110423213B (zh)	2021-06-04	一种阿普斯特衍生物及其制备方法与应用
EP0668276A1 (en)	1995-08-23	2-alkoxy-5,6,7,8-tetrahydroquinoxaline derivative, process for producing the same, and use thereof
JPH01165577A (ja)	1989-06-29	置換されたベンズイミダゾール類およびベンゾチアジアゾール類
US9242938B2 (en)	2016-01-26	Glycine reuptake inhibitor and use thereof