NO312835B1 - Nye piperizin- og piperidinforbindelser, fremgangsmåte for fremstilling derav, anvendelse derav, farmasöytisk sammensetningog fremstilling av denne - Google Patents

Nye piperizin- og piperidinforbindelser, fremgangsmåte for fremstilling derav, anvendelse derav, farmasöytisk sammensetningog fremstilling av denne Download PDF

Info

Publication number: NO312835B1
Authority: NO; Norway
Prior art keywords: formula; compound; mmol; preparation; pyridine
Prior art date: 1997-09-24

Application number

NO19984380A

Other languages

English (en)

Norwegian (no)

Other versions

NO984380L (no

NO984380D0 (no

Inventor

Roelof W Feenstra

Jacobus A J Den Hartog

Cornelis Gerrit Kruse

Martinus Theodorus Maria Tulp

Stephen K Long

Original Assignee

Duphar Int Res

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.)

1997-09-24

Filing date

1998-09-21

Publication date

2002-07-08

1998-09-21 Application filed by Duphar Int Res filed Critical Duphar Int Res

1998-09-21 Publication of NO984380D0 publication Critical patent/NO984380D0/no

1999-03-25 Publication of NO984380L publication Critical patent/NO984380L/no

2002-07-08 Publication of NO312835B1 publication Critical patent/NO312835B1/no

Links

238000000034 method Methods 0.000 title claims description 10
239000008194 pharmaceutical composition Substances 0.000 title claims description 6
239000000825 pharmaceutical preparation Substances 0.000 title claims description 4
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 title description 9
238000002360 preparation method Methods 0.000 title description 5
150000003053 piperidines Chemical class 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims description 43
239000000203 mixture Substances 0.000 claims description 20
238000006243 chemical reaction Methods 0.000 claims description 8
238000004519 manufacturing process Methods 0.000 claims description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
150000003839 salts Chemical class 0.000 claims description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
KVGZZAHHUNAVKZ-UHFFFAOYSA-N 1,4-Dioxin Chemical group O1C=COC=C1 KVGZZAHHUNAVKZ-UHFFFAOYSA-N 0.000 claims description 2
IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 claims description 2
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
208000015114 central nervous system disease Diseases 0.000 claims description 2
229910052736 halogen Inorganic materials 0.000 claims description 2
150000002367 halogens Chemical class 0.000 claims description 2
229910052757 nitrogen Inorganic materials 0.000 claims description 2
125000001424 substituent group Chemical group 0.000 claims description 2
239000000243 solution Substances 0.000 description 25
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
239000003921 oil Substances 0.000 description 15
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
238000001914 filtration Methods 0.000 description 13
239000002904 solvent Substances 0.000 description 13
239000011541 reaction mixture Substances 0.000 description 10
239000007787 solid Substances 0.000 description 10
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
238000001704 evaporation Methods 0.000 description 9
239000000543 intermediate Substances 0.000 description 9
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 8
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 8
239000002274 desiccant Substances 0.000 description 8
230000008020 evaporation Effects 0.000 description 8
239000012044 organic layer Substances 0.000 description 8
238000003818 flash chromatography Methods 0.000 description 7
239000000047 product Substances 0.000 description 7
238000010992 reflux Methods 0.000 description 7
238000003786 synthesis reaction Methods 0.000 description 7
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
239000007864 aqueous solution Substances 0.000 description 6
230000015572 biosynthetic process Effects 0.000 description 6
230000000694 effects Effects 0.000 description 6
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
239000000741 silica gel Substances 0.000 description 5
229910002027 silica gel Inorganic materials 0.000 description 5
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
235000019439 ethyl acetate Nutrition 0.000 description 4
239000012299 nitrogen atmosphere Substances 0.000 description 4
108020003175 receptors Proteins 0.000 description 4
102000005962 receptors Human genes 0.000 description 4
238000003756 stirring Methods 0.000 description 4
102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 3
108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 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
238000001816 cooling Methods 0.000 description 3
239000003480 eluent Substances 0.000 description 3
239000000725 suspension Substances 0.000 description 3
208000024891 symptom Diseases 0.000 description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
WDVDHJLKXYCOFS-UHFFFAOYSA-N (5-bromopyridin-3-yl)methanol Chemical compound OCC1=CN=CC(Br)=C1 WDVDHJLKXYCOFS-UHFFFAOYSA-N 0.000 description 2
IZRZBIMBCUEUNV-UHFFFAOYSA-N (6-phenylpyridin-2-yl)methanol Chemical compound OCC1=CC=CC(C=2C=CC=CC=2)=N1 IZRZBIMBCUEUNV-UHFFFAOYSA-N 0.000 description 2
NIGSUORCHDQXMH-UHFFFAOYSA-N (6-phenylpyridin-2-yl)methyl acetate Chemical compound CC(=O)OCC1=CC=CC(C=2C=CC=CC=2)=N1 NIGSUORCHDQXMH-UHFFFAOYSA-N 0.000 description 2
JFSOSUNPIXJCIX-UHFFFAOYSA-N 1-(2,3-dihydro-1,4-benzodioxin-5-yl)piperazine;hydron;chloride Chemical compound Cl.C1CNCCN1C1=CC=CC2=C1OCCO2 JFSOSUNPIXJCIX-UHFFFAOYSA-N 0.000 description 2
LNUBZXLVNZUZTH-UHFFFAOYSA-N 2-(4-fluorophenyl)-4-methylpyridine Chemical compound CC1=CC=NC(C=2C=CC(F)=CC=2)=C1 LNUBZXLVNZUZTH-UHFFFAOYSA-N 0.000 description 2
ZGLYSZZINMAOFG-UHFFFAOYSA-N 2-methyl-1-oxido-6-phenylpyridin-1-ium Chemical compound CC1=CC=CC(C=2C=CC=CC=2)=[N+]1[O-] ZGLYSZZINMAOFG-UHFFFAOYSA-N 0.000 description 2
NLPHAZLCNNDGPS-UHFFFAOYSA-N 3-bromo-5-(chloromethyl)pyridine Chemical compound ClCC1=CN=CC(Br)=C1 NLPHAZLCNNDGPS-UHFFFAOYSA-N 0.000 description 2
UKKNKIJEEJZWBX-UHFFFAOYSA-N 4-(4-fluorophenyl)-1-oxidopyridin-1-ium Chemical compound C1=C[N+]([O-])=CC=C1C1=CC=C(F)C=C1 UKKNKIJEEJZWBX-UHFFFAOYSA-N 0.000 description 2
ILRZSQPKKVQCKN-UHFFFAOYSA-N 4-(4-fluorophenyl)pyridine-2-carbonitrile Chemical compound C1=CC(F)=CC=C1C1=CC=NC(C#N)=C1 ILRZSQPKKVQCKN-UHFFFAOYSA-N 0.000 description 2
HZAVSUUVXRPHOA-UHFFFAOYSA-N 4-(bromomethyl)-2-(4-fluorophenyl)pyridine Chemical compound C1=CC(F)=CC=C1C1=CC(CBr)=CC=N1 HZAVSUUVXRPHOA-UHFFFAOYSA-N 0.000 description 2
LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
108050004812 Dopamine receptor Proteins 0.000 description 2
102000015554 Dopamine receptor Human genes 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
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
239000007832 Na2SO4 Substances 0.000 description 2
101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
208000020114 Schizophrenia and other psychotic disease Diseases 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 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
229960000583 acetic acid Drugs 0.000 description 2
239000002253 acid Substances 0.000 description 2
235000011114 ammonium hydroxide Nutrition 0.000 description 2
239000000935 antidepressant agent Substances 0.000 description 2
229940005513 antidepressants Drugs 0.000 description 2
239000000164 antipsychotic agent Substances 0.000 description 2
239000002249 anxiolytic agent Substances 0.000 description 2
230000003542 behavioural effect Effects 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
230000002051 biphasic effect Effects 0.000 description 2
210000003169 central nervous system Anatomy 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
201000010099 disease Diseases 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
229960003638 dopamine Drugs 0.000 description 2
PCPIANOJERKFJI-UHFFFAOYSA-N ethyl 5-bromopyridine-3-carboxylate Chemical compound CCOC(=O)C1=CN=CC(Br)=C1 PCPIANOJERKFJI-UHFFFAOYSA-N 0.000 description 2
239000013067 intermediate product Substances 0.000 description 2
239000010410 layer Substances 0.000 description 2
238000002844 melting Methods 0.000 description 2
230000008018 melting Effects 0.000 description 2
QGIVYJIOIXHZDB-UHFFFAOYSA-N methyl 4-(4-fluorophenyl)pyridine-2-carboxylate Chemical compound C1=NC(C(=O)OC)=CC(C=2C=CC(F)=CC=2)=C1 QGIVYJIOIXHZDB-UHFFFAOYSA-N 0.000 description 2
239000003208 petroleum Substances 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
230000004044 response Effects 0.000 description 2
229940076279 serotonin Drugs 0.000 description 2
229910052938 sodium sulfate Inorganic materials 0.000 description 2
235000011152 sodium sulphate Nutrition 0.000 description 2
239000000126 substance Substances 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 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
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
238000005160 1H NMR spectroscopy Methods 0.000 description 1
LSZMVESSGLHDJE-UHFFFAOYSA-N 2-bromo-4-methylpyridine Chemical compound CC1=CC=NC(Br)=C1 LSZMVESSGLHDJE-UHFFFAOYSA-N 0.000 description 1
GREMYQDDZRJQEG-UHFFFAOYSA-N 2-methyl-6-phenylpyridine Chemical compound CC1=CC=CC(C=2C=CC=CC=2)=N1 GREMYQDDZRJQEG-UHFFFAOYSA-N 0.000 description 1
-1 3-(3-fluorophenyl)-5-hydroxymethyl-pyridine hydrochloride Chemical compound 0.000 description 1
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
UKSMMLJBHPMSOV-UHFFFAOYSA-N 4-(4-fluorophenyl)pyridine Chemical compound C1=CC(F)=CC=C1C1=CC=NC=C1 UKSMMLJBHPMSOV-UHFFFAOYSA-N 0.000 description 1
VPPAEYSKEJFLOY-UHFFFAOYSA-N 4-piperazin-1-yl-3h-1,3-benzoxazol-2-one Chemical compound C1=CC=C2OC(=O)NC2=C1N1CCNCC1 VPPAEYSKEJFLOY-UHFFFAOYSA-N 0.000 description 1
FQIUCPGDKPXSLL-UHFFFAOYSA-N 5-bromopyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=CC(Br)=C1 FQIUCPGDKPXSLL-UHFFFAOYSA-N 0.000 description 1
102100022738 5-hydroxytryptamine receptor 1A Human genes 0.000 description 1
101710138638 5-hydroxytryptamine receptor 1A Proteins 0.000 description 1
229910018173 Al—Al Inorganic materials 0.000 description 1
208000019901 Anxiety disease Diseases 0.000 description 1
206010003805 Autism Diseases 0.000 description 1
208000020706 Autistic disease Diseases 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
239000004342 Benzoyl peroxide Substances 0.000 description 1
OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
208000009132 Catalepsy Diseases 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
102000004980 Dopamine D2 Receptors Human genes 0.000 description 1
108090001111 Dopamine D2 Receptors Proteins 0.000 description 1
229940123603 Dopamine D2 receptor antagonist Drugs 0.000 description 1
102000003962 Dopamine D4 receptors Human genes 0.000 description 1
108090000357 Dopamine D4 receptors Proteins 0.000 description 1
101000939500 Homo sapiens UBX domain-containing protein 11 Proteins 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
238000005481 NMR spectroscopy Methods 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
FPJRGVCHJLYDMT-UHFFFAOYSA-N OCC1=CN=CC(C(C=C2)=CC=C2F)=C1.Cl Chemical compound OCC1=CN=CC(C(C=C2)=CC=C2F)=C1.Cl FPJRGVCHJLYDMT-UHFFFAOYSA-N 0.000 description 1
MZUPFHLKQRXPMJ-UHFFFAOYSA-N OCC1=[NH+]C=CC(=C1)C1=CC=C(C=C1)F.[Cl-] Chemical compound OCC1=[NH+]C=CC(=C1)C1=CC=C(C=C1)F.[Cl-] MZUPFHLKQRXPMJ-UHFFFAOYSA-N 0.000 description 1
208000018737 Parkinson disease Diseases 0.000 description 1
NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-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
241000283984 Rodentia Species 0.000 description 1
229910006124 SOCl2 Inorganic materials 0.000 description 1
229910004298 SiO 2 Inorganic materials 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
238000006069 Suzuki reaction reaction Methods 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
102100029645 UBX domain-containing protein 11 Human genes 0.000 description 1
208000012886 Vertigo Diseases 0.000 description 1
206010047853 Waxy flexibility Diseases 0.000 description 1
AGTFTHJYSZRWJK-UHFFFAOYSA-N [5-(4-fluorophenyl)pyridin-3-yl]methanol Chemical compound OCC1=CN=CC(C=2C=CC(F)=CC=2)=C1 AGTFTHJYSZRWJK-UHFFFAOYSA-N 0.000 description 1
235000011054 acetic acid Nutrition 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000016571 aggressive behavior Effects 0.000 description 1
230000008484 agonism Effects 0.000 description 1
239000000556 agonist Substances 0.000 description 1
125000000217 alkyl group Chemical group 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
230000000949 anxiolytic effect Effects 0.000 description 1
229940005530 anxiolytics Drugs 0.000 description 1
VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 1
229960004046 apomorphine Drugs 0.000 description 1
230000006399 behavior Effects 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
235000019400 benzoyl peroxide Nutrition 0.000 description 1
238000009835 boiling Methods 0.000 description 1
KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical class OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
239000012876 carrier material Substances 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
230000009194 climbing Effects 0.000 description 1
230000019771 cognition Effects 0.000 description 1
230000007278 cognition impairment Effects 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
230000001143 conditioned effect Effects 0.000 description 1
239000010779 crude oil Substances 0.000 description 1
239000012043 crude product Substances 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
238000004821 distillation Methods 0.000 description 1
230000003291 dopaminomimetic effect Effects 0.000 description 1
238000001035 drying Methods 0.000 description 1
239000000284 extract Substances 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000006260 foam Substances 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 1
239000007788 liquid Substances 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate 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
239000000463 material Substances 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
230000037361 pathway Effects 0.000 description 1
150000004885 piperazines Chemical class 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
238000000746 purification Methods 0.000 description 1
AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridine hydrochloride Substances [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 1
239000000018 receptor agonist Substances 0.000 description 1
229940044601 receptor agonist Drugs 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
238000006748 scratching Methods 0.000 description 1
230000002393 scratching effect Effects 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008107 starch Substances 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
230000001629 suppression Effects 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
ARYHTUPFQTUBBG-UHFFFAOYSA-N thiophen-2-ylboronic acid Chemical compound OB(O)C1=CC=CS1 ARYHTUPFQTUBBG-UHFFFAOYSA-N 0.000 description 1
238000001665 trituration Methods 0.000 description 1
231100000889 vertigo Toxicity 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- 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
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
- 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Life Sciences & Earth Sciences (AREA)
Biomedical Technology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Chemical Kinetics & Catalysis (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
Hospice & Palliative Care (AREA)
Epidemiology (AREA)
Psychology (AREA)
Otolaryngology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Pyridine Compounds (AREA)

NO19984380A 1997-09-24 1998-09-21 Nye piperizin- og piperidinforbindelser, fremgangsmåte for fremstilling derav, anvendelse derav, farmasöytisk sammensetningog fremstilling av denne NO312835B1 (no)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
EP97202950		1997-09-24

Publications (3)

Publication Number	Publication Date
NO984380D0 NO984380D0 (no)	1998-09-21
NO984380L NO984380L (no)	1999-03-25
NO312835B1 true NO312835B1 (no)	2002-07-08

Family

ID=8228755

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19984380A NO312835B1 (no)	1997-09-24	1998-09-21	Nye piperizin- og piperidinforbindelser, fremgangsmåte for fremstilling derav, anvendelse derav, farmasöytisk sammensetningog fremstilling av denne

Country Status (30)

Country	Link
US (2)	US6090812A (de)
EP (1)	EP0908458B1 (de)
JP (1)	JP4191826B2 (de)
KR (1)	KR100632188B1 (de)
CN (1)	CN1093857C (de)
AR (1)	AR017127A1 (de)
AT (1)	ATE316529T1 (de)
AU (1)	AU733526B2 (de)
BR (1)	BR9803497A (de)
CA (1)	CA2247734C (de)
CY (1)	CY1107494T1 (de)
CZ (1)	CZ296741B6 (de)
DE (1)	DE69833297T2 (de)
DK (1)	DK0908458T3 (de)
DZ (1)	DZ2613A1 (de)
ES (1)	ES2255127T3 (de)
HU (1)	HU227422B1 (de)
ID (1)	ID20895A (de)
IL (1)	IL126295A (de)
NO (1)	NO312835B1 (de)
NZ (1)	NZ331984A (de)
PL (1)	PL190622B1 (de)
PT (1)	PT908458E (de)
RU (1)	RU2197488C2 (de)
SI (1)	SI0908458T1 (de)
SK (1)	SK285205B6 (de)
TR (1)	TR199801866A1 (de)
TW (1)	TW530054B (de)
UA (1)	UA66756C2 (de)
ZA (1)	ZA988749B (de)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6200994B1 (en)	1999-01-07	2001-03-13	American Home Products Corp	1,4-Disubstituted cyclohexane derivatives for the treatment of depression
ATE223406T1 (de) *	1999-01-07	2002-09-15	Wyeth Corp	1,4-disubstitutierte cyclohexanderivate zur behandlung von depression
DE10005150A1 (de) *	2000-02-07	2001-08-09	Merck Patent Gmbh	Verfahren zur Herstellung von 5-Arylnicotinaldehyden
US6911448B2 (en) *	2000-05-12	2005-06-28	Solvay Pharmaceuticals B.V.	Piperazine and piperidine compounds
DE10115922A1 (de) *	2001-03-30	2002-10-10	Bayer Ag	Cyclisch substituierte 2-Thio-3,5-dicyano-4-aryl-6-aminopyridine und ihre Verwendung
US7504395B2 (en) *	2001-07-20	2009-03-17	Psychogenics, Inc.	Treatment for attention-deficit hyperactivity disorder
US7435738B2 (en)	2003-08-18	2008-10-14	Solvay Pharmaceuticals, Inc.	Stable crystalline form of bifeprunox mesylate (7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate)
US7405216B2 (en)	2004-08-18	2008-07-29	Solvay Pharmaceuticals, B.V.	Stable crystalline form of bifeprunox mesylate (7-[4-([1,1′-biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone monomethanesulfonate)
US7423040B2 (en)	2005-02-18	2008-09-09	Irene Eijgendaal	Stable crystalline form of bifeprunox mesylate, dosage forms thereof and methods for using same
US7964604B2 (en)	2005-02-18	2011-06-21	Solvay Pharmaceuticals B.V.	Bifeprunox mesylate maintenance dose compositions and methods for using the same
AU2007247251B2 (en)	2006-05-02	2011-11-03	Solvay Pharmaceuticals B.V.	N-oxides of pyridylmethylpiperazine and -piperidine derivatives
US20070275977A1 (en) *	2006-05-02	2007-11-29	Van Aar Marcel P	N-oxides of pyridylmethyl -piperazine and -piperidine derivatives
US7786126B2 (en)	2006-06-16	2010-08-31	Solvay Pharmaceuticals B.V.	Combination preparations comprising SLV308 and a dopamine agonist
US8106056B2 (en)	2006-06-16	2012-01-31	Solvay Pharmaceuticals B.V.	Combination preparations comprising bifeprunox and a dopamine agonist
WO2011088838A1 (en)	2010-01-25	2011-07-28	H. Lundbeck A/S	Novel 6,6a,7,8,9,10-hexahydro-4h-4,8,10a-triaza-acephenanthrylene derivatives as dopamine d2 ligands
US8877778B2 (en) *	2010-12-15	2014-11-04	Hoffmann-La Roche Inc.	Benzofurane compounds
US8921397B2 (en)	2011-05-04	2014-12-30	Hoffmann-La Roche Inc.	Benzofurane-piperidine compounds
JP7030776B2 (ja)	2016-07-20	2022-03-07	ノバルティスアーゲー	アミノピリジン誘導体およびそれらの選択的ａｌｋ－２阻害剤としての使用
KR101665971B1 (ko)	2016-08-10	2016-10-13	(주)글로벌 로보틱스	차량용 발포패드 부착장치
BR112022009710A2 (pt)	2019-11-22	2022-08-09	Incyte Corp	Terapia de combinação compreendendo um inibidor de alk2 e um inibidor de jak2
CA3187767A1 (en)	2020-06-16	2021-12-23	Incyte Corporation	Alk2 inhibitors for the treatment of anemia

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0190472B1 (de) *	1984-12-21	1989-07-12	Duphar International Research B.V	Arzneimittel mit antipsychotischer Wirkung
DE3586794T2 (de)	1984-12-21	1993-05-27	Duphar Int Res	Arzneimittel mit psychotroper wirkung.
DK93087A (da) *	1986-02-27	1987-08-28	Duphar Int Res	Hidtil ukendte aryl substituerede (n-piperidinyl)methyl- og (n-piperazinyl)methylazoler med antipsykotiske egenskaber
EP0508347A1 (de) *	1991-04-10	1992-10-14	Hoechst Aktiengesellschaft	5,7-Dihydroxy-2-Methyl-8-[4-(3-Hydroxy-1-(1-Propyl))Piperidinyl]-4H-1-Benzopyran-4-on, seine Herstellung und Verwendung
NZ240863A (en) *	1991-09-11	1995-04-27	Mcneilab Inc	Substituted 4-aryl piperidine and 4-aryl piperazine derivatives, preparation and pharmaceutical compositions thereof
JPH05262765A (ja) *	1992-03-18	1993-10-12	Sumitomo Chem Co Ltd	ベンゾフラン誘導体およびそれを有効成分とする除草剤
FR2692264B1 (fr)	1992-06-12	1994-08-05	Adir	Nouvelles piperazines 1,4-disubstituees, leur procede de preparation et les compositions pharmaceutiques les contenant.
US5332732A (en) *	1992-09-11	1994-07-26	Mcneilab, Inc.	Thiophene and pyridine antipsychotic agents
US5436246A (en) *	1992-09-17	1995-07-25	Merrell Dow Pharmaceuticals Inc.	Serotonin receptor agents
RU2118322C1 (ru) *	1993-07-05	1998-08-27	Дюфар Интернэшнл Рисерч Б.В.	2,3-дигидро-1,4-бензодиокси-5-ил-пиперазиновые производные или их соли
GB9314758D0 (en) *	1993-07-16	1993-08-25	Wyeth John & Brother Ltd	Heterocyclic derivatives
EP0650964A1 (de)	1993-11-02	1995-05-03	Duphar International Research B.V	1- 2H-1-Benzopyran-2-on-8-yl -Piperazin Derivate
DE4425146A1 (de)	1994-07-15	1996-01-18	Basf Ag	Verwendung heterocyclischer Verbindungen
US5607936A (en) *	1994-09-30	1997-03-04	Merck & Co., Inc.	Substituted aryl piperazines as neurokinin antagonists
DE69615376T2 (de) *	1995-07-13	2002-09-05	Knoll Gmbh	Piperazin-derivate als heilmittel
AU708053B2 (en) *	1996-03-29	1999-07-29	Duphar International Research B.V.	Piperazine and piperidine compounds
DE19637237A1 (de) *	1996-09-13	1998-03-19	Merck Patent Gmbh	Piperazin-Derivate

1998
- 1998-09-11 TW TW087115179A patent/TW530054B/zh not_active IP Right Cessation
- 1998-09-18 IL IL12629598A patent/IL126295A/xx not_active IP Right Cessation
- 1998-09-21 ID IDP981269A patent/ID20895A/id unknown
- 1998-09-21 AT AT98203154T patent/ATE316529T1/de active
- 1998-09-21 CN CN98119652A patent/CN1093857C/zh not_active Expired - Fee Related
- 1998-09-21 AU AU86079/98A patent/AU733526B2/en not_active Ceased
- 1998-09-21 CZ CZ0303098A patent/CZ296741B6/cs not_active IP Right Cessation
- 1998-09-21 TR TR1998/01866A patent/TR199801866A1/xx unknown
- 1998-09-21 PT PT98203154T patent/PT908458E/pt unknown
- 1998-09-21 DE DE69833297T patent/DE69833297T2/de not_active Expired - Lifetime
- 1998-09-21 PL PL98328754A patent/PL190622B1/pl not_active IP Right Cessation
- 1998-09-21 CA CA002247734A patent/CA2247734C/en not_active Expired - Fee Related
- 1998-09-21 DK DK98203154T patent/DK0908458T3/da active
- 1998-09-21 ES ES98203154T patent/ES2255127T3/es not_active Expired - Lifetime
- 1998-09-21 HU HU9802129A patent/HU227422B1/hu not_active IP Right Cessation
- 1998-09-21 SK SK1294-98A patent/SK285205B6/sk not_active IP Right Cessation
- 1998-09-21 AR ARP980104704A patent/AR017127A1/es active IP Right Grant
- 1998-09-21 BR BR9803497-9A patent/BR9803497A/pt not_active IP Right Cessation
- 1998-09-21 KR KR1019980038929A patent/KR100632188B1/ko not_active Expired - Fee Related
- 1998-09-21 NZ NZ331984A patent/NZ331984A/en not_active IP Right Cessation
- 1998-09-21 SI SI9830822T patent/SI0908458T1/sl unknown
- 1998-09-21 NO NO19984380A patent/NO312835B1/no not_active IP Right Cessation
- 1998-09-21 RU RU98117621/04A patent/RU2197488C2/ru not_active IP Right Cessation
- 1998-09-21 EP EP98203154A patent/EP0908458B1/de not_active Expired - Lifetime
- 1998-09-21 JP JP28357898A patent/JP4191826B2/ja not_active Expired - Lifetime
- 1998-09-22 DZ DZ980223A patent/DZ2613A1/xx active
- 1998-09-22 US US09/158,520 patent/US6090812A/en not_active Ceased
- 1998-09-22 UA UA98094970A patent/UA66756C2/uk unknown
- 1998-09-23 ZA ZA988749A patent/ZA988749B/xx unknown
2006
- 2006-04-07 CY CY20061100484T patent/CY1107494T1/el unknown
2008
- 2008-04-18 US US12/081,710 patent/USRE41425E1/en not_active Expired - Lifetime

Also Published As

Publication number	Publication date
HU227422B1 (en)	2011-05-30
CN1220265A (zh)	1999-06-23
AU733526B2 (en)	2001-05-17
DE69833297T2 (de)	2006-07-20
ATE316529T1 (de)	2006-02-15
TR199801866A1 (xx)	1999-04-21
AU8607998A (en)	1999-04-15
IL126295A (en)	2003-02-12
SI0908458T1 (sl)	2006-06-30
AR017127A1 (es)	2001-08-22
BR9803497A (pt)	2000-05-02
JPH11302279A (ja)	1999-11-02
KR100632188B1 (ko)	2007-04-25
PL190622B1 (pl)	2005-12-30
DE69833297D1 (de)	2006-04-13
ES2255127T3 (es)	2006-06-16
IL126295A0 (en)	1999-05-09
CA2247734A1 (en)	1999-03-24
ZA988749B (en)	1999-03-26
KR19990029982A (ko)	1999-04-26
PL328754A1 (en)	1999-03-29
NO984380L (no)	1999-03-25
CA2247734C (en)	2007-08-07
NO984380D0 (no)	1998-09-21
US6090812A (en)	2000-07-18
PT908458E (pt)	2006-05-31
UA66756C2 (uk)	2004-06-15
EP0908458B1 (de)	2006-01-25
NZ331984A (en)	2000-02-28
JP4191826B2 (ja)	2008-12-03
CN1093857C (zh)	2002-11-06
HK1018272A1 (en)	1999-12-17
CZ303098A3 (cs)	1999-04-14
DZ2613A1 (fr)	2003-03-01
SK285205B6 (sk)	2006-08-03
CZ296741B6 (cs)	2006-06-14
SK129498A3 (en)	1999-04-13
DK0908458T3 (da)	2006-06-06
HU9802129D0 (en)	1998-11-30
HUP9802129A1 (hu)	2000-03-28
TW530054B (en)	2003-05-01
CY1107494T1 (el)	2013-03-13
RU2197488C2 (ru)	2003-01-27
ID20895A (id)	1999-03-25
EP0908458A1 (de)	1999-04-14
USRE41425E1 (en)	2010-07-06

Legal Events

Date	Code	Title	Description
2013-04-22	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
USRE41425E1 (en)	2010-07-06	Piperazine and piperidine compounds
RU2178414C2 (ru)	2002-01-20	Производные пиперазина и пиперидина и способ их получения
EP2041111A1 (de)	2009-04-01	Neue pyridinanaloga
JP2021529740A (ja)	2021-11-04	サイクリン依存性キナーゼの阻害剤
Cale Jr et al.	1989	Benzo-and pyrido-1, 4-oxazepin-5-ones and-thiones: Synthesis and structure-activity relationships of a new series of H1-antihistamines
NL8501826A (nl)	1986-01-16	Nieuwe 1,4-dihydropyridinederivaten en zouten daarvan, werkwijze voor het bereiden van deze derivaten en zouten en farmaceutische preparaten die ze bevatten.
CA2289572A1 (en)	1999-02-04	Novel hexahydro-1,4-diazepine derivatives or salts thereof
NO320531B1 (no)	2005-12-19	3-tetrahydropyridin-4-yl-indoler, fremgangsmate for fremstilling, farmasoytisk sammensetning, fremgangsmate for fremstilling av denne samt anvendelse av indolene
JPH04300880A (ja)	1992-10-23	クロマン誘導体
CA2255165A1 (en)	1999-06-08	Benzothiophene derivatives useful in therapy
NO323781B1 (no)	2007-07-02	Nye fenylpiperaziner, fremgangsmate for fremstilling derav, farmasoytisk preparat inneholdende minst en slik forbindelse samt anvendelse av forbindelsene.
EP1530567A1 (de)	2005-05-18	Pyridinyl-substituierte (1,2,3)triazole als inhibitoren des tgf-beta signalweges
HK1018272B (en)	2006-04-13	Substituted pyridylmethylpiperazine and piperidine derivatives, their preparation and their use for treating central nervous system (cns) disorders
KR100458346B1 (ko)	2005-06-21	피페라진및피페리딘화합물