DK169923B1 - 3-[[4-(1,2-benzisoxazol-3-yl)-1-piperidinyl]alkyl]-6,7,8,9-tetrahydro-2-alkyl-4H-pyrido[1,2-a]pyrimidin-4-on-forbindelser, fremgangsmåde til fremstilling deraf og antipsykotiske præparater indeholdende disse - Google Patents

3-[[4-(1,2-benzisoxazol-3-yl)-1-piperidinyl]alkyl]-6,7,8,9-tetrahydro-2-alkyl-4H-pyrido[1,2-a]pyrimidin-4-on-forbindelser, fremgangsmåde til fremstilling deraf og antipsykotiske præparater indeholdende disse Download PDF

Info

Publication number: DK169923B1
Authority: DK; Denmark
Prior art keywords: formula; compounds; alkyl; alk; parts
Prior art date: 1988-11-07

Application number

DK551989A

Other languages

Danish (da)

English (en)

Other versions

DK551989D0 (da

DK551989A (da

Inventor

Cornelus Gerardus Mari Janssen

Alfonsus Guilielmus Knaeps

Ludo Edmond Josephine Kennis

Jan Vandenberk

Original Assignee

Janssen Pharmaceutica Nv

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.)

1988-11-07

Filing date

1989-11-06

Publication date

1995-04-03

1989-11-06 Application filed by Janssen Pharmaceutica Nv filed Critical Janssen Pharmaceutica Nv

1989-11-06 Publication of DK551989D0 publication Critical patent/DK551989D0/da

1990-05-08 Publication of DK551989A publication Critical patent/DK551989A/da

1995-04-03 Application granted granted Critical

1995-04-03 Publication of DK169923B1 publication Critical patent/DK169923B1/da

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 84
-1 1,2-benzisoxazol-3-yl Chemical group 0.000 title claims description 45
125000000217 alkyl group Chemical group 0.000 title claims description 18
238000002360 preparation method Methods 0.000 title claims description 12
230000000561 anti-psychotic effect Effects 0.000 title claims description 6
238000000034 method Methods 0.000 title abstract description 21
230000008569 process Effects 0.000 title description 4
239000002253 acid Substances 0.000 claims abstract description 32
150000003839 salts Chemical class 0.000 claims abstract description 26
239000004480 active ingredient Substances 0.000 claims abstract description 19
239000001257 hydrogen Substances 0.000 claims abstract description 9
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 9
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract 3
239000000203 mixture Substances 0.000 claims description 56
238000006243 chemical reaction Methods 0.000 claims description 22
239000003153 chemical reaction reagent Substances 0.000 claims description 20
239000002585 base Substances 0.000 claims description 16
239000012442 inert solvent Substances 0.000 claims description 14
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
229910052736 halogen Inorganic materials 0.000 claims description 10
150000002367 halogens Chemical class 0.000 claims description 10
150000002923 oximes Chemical class 0.000 claims description 10
PMXMIIMHBWHSKN-UHFFFAOYSA-N 3-{2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl}-9-hydroxy-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one Chemical group FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCC(O)C4=NC=3C)=NOC2=C1 PMXMIIMHBWHSKN-UHFFFAOYSA-N 0.000 claims description 7
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 6
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
150000002431 hydrogen Chemical class 0.000 claims description 5
239000003513 alkali Substances 0.000 claims description 4
239000003795 chemical substances by application Substances 0.000 claims description 3
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
231100000252 nontoxic Toxicity 0.000 claims description 3
230000003000 nontoxic effect Effects 0.000 claims description 3
125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
125000002889 tridecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 2
150000001409 amidines Chemical class 0.000 claims description 2
150000002081 enamines Chemical class 0.000 claims description 2
239000012458 free base Substances 0.000 claims description 2
230000002152 alkylating effect Effects 0.000 claims 1
229940005529 antipsychotics Drugs 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
239000003196 psychodysleptic agent Substances 0.000 claims 1
239000008194 pharmaceutical composition Substances 0.000 abstract description 6
FFESGTAUFAZQRI-UHFFFAOYSA-N 3-piperidin-1-yl-1,2-benzoxazole Chemical class C1CCCCN1C1=NOC2=CC=CC=C12 FFESGTAUFAZQRI-UHFFFAOYSA-N 0.000 abstract description 3
239000000164 antipsychotic agent Substances 0.000 abstract description 2
125000001475 halogen functional group Chemical group 0.000 abstract 1
125000004435 hydrogen atom Chemical class [H]* 0.000 abstract 1
125000004356 hydroxy functional group Chemical group O* 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
239000000243 solution Substances 0.000 description 36
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 35
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
239000000543 intermediate Substances 0.000 description 27
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 19
229960001701 chloroform Drugs 0.000 description 19
239000003480 eluent Substances 0.000 description 18
239000000047 product Substances 0.000 description 17
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
239000011541 reaction mixture Substances 0.000 description 16
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 14
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 12
238000003756 stirring Methods 0.000 description 12
APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 12
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
239000002904 solvent Substances 0.000 description 10
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
238000007126 N-alkylation reaction Methods 0.000 description 9
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 9
229960004046 apomorphine Drugs 0.000 description 9
238000004440 column chromatography Methods 0.000 description 9
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
239000000741 silica gel Substances 0.000 description 9
229910002027 silica gel Inorganic materials 0.000 description 9
238000012360 testing method Methods 0.000 description 9
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
238000010992 reflux Methods 0.000 description 8
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 8
239000003826 tablet Substances 0.000 description 8
239000000010 aprotic solvent Substances 0.000 description 7
150000002148 esters Chemical class 0.000 description 7
RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
125000004432 carbon atom Chemical group C* 0.000 description 6
239000003054 catalyst Substances 0.000 description 6
239000000284 extract Substances 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 5
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 5
241000282472 Canis lupus familiaris Species 0.000 description 5
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 5
229910052784 alkaline earth metal Inorganic materials 0.000 description 5
150000004945 aromatic hydrocarbons Chemical class 0.000 description 5
125000003118 aryl group Chemical group 0.000 description 5
238000001816 cooling Methods 0.000 description 5
239000002552 dosage form Substances 0.000 description 5
150000008282 halocarbons Chemical class 0.000 description 5
239000000376 reactant Substances 0.000 description 5
238000007363 ring formation reaction Methods 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 4
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
239000002202 Polyethylene glycol Substances 0.000 description 4
208000028017 Psychotic disease Diseases 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
238000005917 acylation reaction Methods 0.000 description 4
230000029936 alkylation Effects 0.000 description 4
238000005804 alkylation reaction Methods 0.000 description 4
239000002775 capsule Substances 0.000 description 4
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MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
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201000010099 disease Diseases 0.000 description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
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150000003930 2-aminopyridines Chemical class 0.000 description 3
OMQHDIHZSDEIFH-UHFFFAOYSA-N 3-Acetyldihydro-2(3H)-furanone Chemical compound CC(=O)C1CCOC1=O OMQHDIHZSDEIFH-UHFFFAOYSA-N 0.000 description 3
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HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
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238000004811 liquid chromatography Methods 0.000 description 3
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 3
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239000004310 lactic acid Substances 0.000 description 1
150000004668 long chain fatty acids Chemical class 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
238000012423 maintenance Methods 0.000 description 1
229960002510 mandelic acid Drugs 0.000 description 1
125000002960 margaryl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000002609 medium Substances 0.000 description 1
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
206010027599 migraine Diseases 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000002156 mixing Methods 0.000 description 1
125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
DISPOJHKKXSCLS-UHFFFAOYSA-N n-diaminophosphorylmethanamine Chemical compound CNP(N)(N)=O DISPOJHKKXSCLS-UHFFFAOYSA-N 0.000 description 1
230000000701 neuroleptic effect Effects 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
125000001196 nonadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
235000020824 obesity Nutrition 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000002674 ointment Substances 0.000 description 1
239000006186 oral dosage form Substances 0.000 description 1
229940098462 oral drops Drugs 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
125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 1
125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
239000003961 penetration enhancing agent Substances 0.000 description 1
125000002958 pentadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
238000003408 phase transfer catalysis Methods 0.000 description 1
239000003444 phase transfer catalyst Substances 0.000 description 1
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
238000000053 physical method Methods 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 description 1
229940068918 polyethylene glycol 400 Drugs 0.000 description 1
235000011181 potassium carbonates Nutrition 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
239000001294 propane Substances 0.000 description 1
239000003380 propellant Substances 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
NYJWYCAHJRGKMI-UHFFFAOYSA-N pyrido[1,2-a]pyrimidin-4-one Chemical class C1=CC=CN2C(=O)C=CN=C21 NYJWYCAHJRGKMI-UHFFFAOYSA-N 0.000 description 1
238000001959 radiotherapy Methods 0.000 description 1
230000009467 reduction Effects 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
201000000980 schizophrenia Diseases 0.000 description 1
230000000391 smoking effect Effects 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
235000011121 sodium hydroxide Nutrition 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
239000003549 soybean oil Substances 0.000 description 1
235000012424 soybean oil Nutrition 0.000 description 1
239000004544 spot-on Substances 0.000 description 1
125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
239000004575 stone Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 1
229940124530 sulfonamide Drugs 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
238000007910 systemic administration Methods 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000010998 test method Methods 0.000 description 1
125000005207 tetraalkylammonium group Chemical group 0.000 description 1
125000005497 tetraalkylphosphonium group Chemical group 0.000 description 1
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
150000003626 triacylglycerols Chemical class 0.000 description 1
FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
YFNKIDBQEZZDLK-UHFFFAOYSA-N triglyme Chemical compound COCCOCCOCCOC YFNKIDBQEZZDLK-UHFFFAOYSA-N 0.000 description 1
238000001665 trituration Methods 0.000 description 1
208000019553 vascular disease Diseases 0.000 description 1
239000005526 vasoconstrictor agent Substances 0.000 description 1
235000012431 wafers Nutrition 0.000 description 1
230000004580 weight loss Effects 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- 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
- A61P25/02—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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Psychiatry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

DK551989A 1988-11-07 1989-11-06 3-[[4-(1,2-benzisoxazol-3-yl)-1-piperidinyl]alkyl]-6,7,8,9-tetrahydro-2-alkyl-4H-pyrido[1,2-a]pyrimidin-4-on-forbindelser, fremgangsmåde til fremstilling deraf og antipsykotiske præparater indeholdende disse DK169923B1 (da)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US26785788A	1988-11-07	1988-11-07
US26785788		1988-11-07

Publications (3)

Publication Number	Publication Date
DK551989D0 DK551989D0 (da)	1989-11-06
DK551989A DK551989A (da)	1990-05-08
DK169923B1 true DK169923B1 (da)	1995-04-03

Family

ID=23020416

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DK551989A DK169923B1 (da)	1988-11-07	1989-11-06	3-[[4-(1,2-benzisoxazol-3-yl)-1-piperidinyl]alkyl]-6,7,8,9-tetrahydro-2-alkyl-4H-pyrido[1,2-a]pyrimidin-4-on-forbindelser, fremgangsmåde til fremstilling deraf og antipsykotiske præparater indeholdende disse

Country Status (21)

Country	Link
EP (1)	EP0368388B1 (fr)
JP (1)	JP2758045B2 (fr)
KR (1)	KR0146053B1 (fr)
AT (1)	ATE122349T1 (fr)
AU (1)	AU614437B2 (fr)
CA (1)	CA2000786C (fr)
CL (1)	CL43432B (fr)
CY (2)	CY1926A (fr)
DE (2)	DE68922577T2 (fr)
DK (1)	DK169923B1 (fr)
ES (1)	ES2075036T3 (fr)
FI (1)	FI92201C (fr)
HK (1)	HK131696A (fr)
IE (1)	IE66370B1 (fr)
IL (1)	IL92208A0 (fr)
LU (1)	LU91362I2 (fr)
NL (1)	NL300298I2 (fr)
NO (2)	NO173015C (fr)
NZ (1)	NZ231062A (fr)
PT (1)	PT92206B (fr)
ZA (1)	ZA898436B (fr)

Families Citing this family (61)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9008850D0 (en) *	1990-04-19	1990-06-13	Janssen Pharmaceutica Nv	Novel 2,9-disubstituted-4h-pyridol(1,2-a)pyrimidin-4-ones
US5378714A (en) *	1991-11-27	1995-01-03	Novo Nordisk A/S	Antipsychotic piperidine derivatives
JPH07502268A (ja) *	1991-11-27	1995-03-09	ノボ　ノルディスク　アクティーゼルスカブ	化学化合物、それらの製法および使用
ES2050069B1 (es) *	1992-07-10	1994-12-16	Vita Invest Sa	Procedimiento para la obtencion de 3-(2-(4-(6-fluoro-1,2-benzisoxazol-3-il)piperidino)etil)-2-metil-6,7,8,9-tetrahidro-4h-pirido(1,2-a) pirimidin-4-ona.
DK60793D0 (da) *	1993-05-26	1993-05-26	Novo Nordisk As	Kemiske forbindelser, deres fremstilling og anvendelse
DK60593D0 (da) *	1993-05-26	1993-05-26	Novo Nordisk As	Kemiske forbindelser, deres fremstilling og anvendelse
CN1074923C (zh)	1993-11-19	2001-11-21	詹森药业有限公司	微囊密封的3-哌啶基取代的1,2-苯并异唑类和1,2-苯并异噻唑类
ES2137486T3 (es) *	1993-11-23	1999-12-16	Janssen Pharmaceutica Nv	Derivados de 9-hidroxi-pirido(1,2-a)pirimidin-4-ona-eter.
ES2085234B1 (es) *	1994-02-24	1997-01-16	Vita Invest Sa	Agente activo sobre el sistema nervioso central, procedimiento para su preparacion y composiciones farmaceuticas que lo contienen.
TW487572B (en) *	1996-05-20	2002-05-21	Janssen Pharmaceutica Nv	Aqueous suspensions of 9-hydroxyrisperidone fatty acid esters
US6028083A (en) *	1997-07-25	2000-02-22	Hoechst Marion Roussel, Inc.	Esters of (+)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl) ethyl]-4-piperidinemethanol
UA72189C2 (uk) *	1997-11-17	2005-02-15	Янссен Фармацевтика Н.В.	Фармацевтична композиція, що містить водну суспензію субмікронних ефірів 9-гідроксирисперидон жирних кислот
ES2141671B1 (es) *	1997-12-26	2001-01-01	Vita Invest Sa	Compuesto pirimidinico activo sobre el sistema nervioso central, procedimiento para su preparacion y composiciones farmaceuticas que lo contienen.
US6500833B1 (en)	1998-05-18	2002-12-31	Sepracor Inc.	(+)-Hydroxyrisperidone compositions and methods
US6326362B1 (en)	1998-05-18	2001-12-04	Sepracor Inc.	(-)-phosphonorisperidone and (-)-sulforisperidone compositions and methods
US6342488B1 (en)	1998-08-18	2002-01-29	Sepracor, Inc.	Phosphonorisperidone and sulforisperidone compositions and methods
ES2197801B1 (es) *	2002-03-05	2005-03-16	Ferrer Internacional,S.A	Procedimiento de obtencion de la 3-(2-(4-(6-fluoro-benzo(d)isoxazol-3-il) piperidin-1-il)-etil)-2-metil-6,7,8,9-tetrahidro-4h-pirido-(1,2-a ) pirimidin-4-ona.
KR20040025224A (ko) *	2002-09-18	2004-03-24	주식회사 대웅	2-(2-메틸-4-옥소-6,7,8,9-테트라하이드로-4Ｈ-피리도[1,2-ａ]피리미딘-3-일)아세트알데히드 및 그 제조방법
CN100390146C (zh)	2002-11-13	2008-05-28	斯索恩有限公司	制备利培酮的方法和用于该方法的中间体
EP1791839B1 (fr)	2004-09-09	2015-06-10	Janssen Pharmaceutica NV	PREPARATION DE 9-HYDROXY-3-(2-HYDROXYETHYL)-2-METHYL-4H-PYRIDO[1,2-a]PYRIMIDIN-4-ONE ET LEURS CRISTAUX
US20070197591A1 (en)	2005-12-12	2007-08-23	Sandra Boom	Use of paliperidone for the treatment of a mental disorder in a psychiatric patient with reduced hepatic function
EP2133351A3 (fr) *	2006-08-14	2010-01-13	Teva Pharmaceutical Industries Ltd.	Forme cristalline de la 9-hydroxy-rispéridone (palipéridone)
EP2133352A3 (fr) *	2006-08-14	2010-01-13	Teva Pharmaceutical Industries Ltd.	Forme cristalline de la 9-hydroxy-rispéridone (palipéridone)
US20080177067A1 (en) *	2006-08-14	2008-07-24	Ben-Zion Dolitzky	Crystal forms of 9-hydroxy-risperidone (paliperidone)
JP2009524574A (ja) *	2006-08-23	2009-07-02	テバファーマシューティカルインダストリーズリミティド	Ｃｍｈｔｐ及びその中間体の合成方法
US7820816B2 (en)	2006-08-23	2010-10-26	Teva Pharmaceutical Industries Ltd.	Process for the synthesis of CMHTP and intermediates thereof
WO2008087557A2 (fr) *	2007-01-08	2008-07-24	Actavis Group Ptc Ehf	Procédé amélioré de préparation de chlorhydrate de 9-hydroxy-3-(2-chloroéthyl)- 2-méthyl-4h-pyrido[1,2-a]pyrimidin-4-one
JP5315336B2 (ja) *	2007-04-19	2013-10-16	又欣李	精神疾患治療用の新規化合物とその調剤及び使用
WO2009010988A1 (fr) *	2007-07-19	2009-01-22	Natco Pharma Limited	Procédé amélioré, industriellement viable pour la préparation de palipéridone de haute pureté
WO2009015828A1 (fr) *	2007-07-27	2009-02-05	Synthon B.V.	Dérivés de palipéridone
WO2009045489A2 (fr) *	2007-10-03	2009-04-09	Teva Pharmaceutical Industries Ltd.	Procédé de synthèse de cmhtp, un intermédiaire de la palipéridone
NZ584370A (en) *	2007-10-09	2011-04-29	Cipla Ltd	Processes for the preparation of paliperidone and pharmaceutically acceptable salts thereof and intermediates for use in the processes
EP2235009B1 (fr)	2007-12-10	2013-10-30	Synthon B.V.	Synthèse de palipéridone
US20100311969A1 (en) *	2008-02-05	2010-12-09	Watson Pharma Private Limited	Process For Preparation of Paliperidone
EP2285804A4 (fr) *	2008-04-21	2011-09-14	Glenmark Generics Ltd	Procédé pour la fabrication d'intermédiaires de palipéridone
US8309717B2 (en)	2008-05-29	2012-11-13	Inke, S.A.	Process to prepare paliperidone and intermediates thereof
US8481729B2 (en)	2008-06-16	2013-07-09	Msn Laboratories Limited	Processes for the preparation of paliperidone
EP2321311B1 (fr) *	2008-07-11	2012-09-19	Synthon B.V.	Synthèse de palipéridone
WO2010003703A2 (fr) *	2008-07-11	2010-01-14	Synthon B.V.	Palipéridone cétone
SI22856A (sl) *	2008-07-31	2010-02-26	Krka, Tovarna Zdravil, D.D., Novo Mesto	Proces za pripravo paliperidona
EP2161019A1 (fr)	2008-09-05	2010-03-10	KRKA, D.D., Novo Mesto	Composition pharmaceutique multi-particules à libération prolongée comportant de la palipéridone
EP2199293A1 (fr)	2008-12-22	2010-06-23	Chemo Ibérica, S.A.	Procédé à étape unique pour la préparation de palipéridone en son sel d'oxalate
EP2202234A1 (fr)	2008-12-24	2010-06-30	Laboratorios Lesvi, S.L.	Purification de la palipéridone
EP2275423B9 (fr)	2009-07-13	2012-08-15	KRKA, d.d., Novo mesto	Procédé de synthèse de palipéridone
WO2011018246A2 (fr)	2009-08-13	2011-02-17	Synthon B.V.	Composition de palipéridone à libération contrôlée
EP2343296A1 (fr)	2009-12-01	2011-07-13	Chemo Ibérica, S.A.	Procédé pour la purification de la palipéridone
US20120259116A1 (en) *	2009-12-17	2012-10-11	Rajiv Kumar	Novel Process for the Preparation of Paliperidone
US8088594B2 (en) *	2010-03-16	2012-01-03	Saladax Biomedical Inc.	Risperidone immunoassay
WO2012035554A1 (fr) *	2010-09-14	2012-03-22	Megafine Pharma (P) Ltd.	Procédé amélioré de préparation de palipéridone très pure
EP3034079B1 (fr)	2010-11-15	2018-01-10	Agenebio, Inc.	Dérivés de pyridazine, compositions et méthodes de traitement d'une déficience cognitive
CN102153552B (zh) *	2011-03-01	2012-08-22	吉林大学	两种帕潘立酮药物共晶及其制备方法
CN102206210B (zh) *	2011-04-01	2014-07-02	常州市第四制药厂有限公司	一种6-氟-3-(4-哌啶基)-1，2-苯并异噁唑盐酸盐的生产方法
US20140206667A1 (en)	2012-11-14	2014-07-24	Michela Gallagher	Methods and compositions for treating schizophrenia
EP3083569B1 (fr)	2013-12-20	2022-01-26	Agenebio, Inc.	Dérivés de benzodiazépine, compositions et procédés de traitement de la déficience cognitive
JP6987384B2 (ja)	2015-06-19	2021-12-22	エージンバイオ，インコーポレイテッド	ベンゾジアゼピン誘導体、組成物、および認知障害を処置するための方法
US20180170941A1 (en)	2016-12-19	2018-06-21	Agenebio, Inc.	Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment
US11505555B2 (en)	2016-12-19	2022-11-22	Agenebio, Inc.	Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment
US11377445B2 (en)	2018-02-21	2022-07-05	Zenvision Pharma Llp	Derivatives of paliperidone and process for the preparation thereof
US11414425B2 (en)	2018-06-19	2022-08-16	Agenebio, Inc.	Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment
WO2024039886A1 (fr)	2022-08-19	2024-02-22	Agenebio, Inc.	Dérivés de benzoazépine, compositions et méthodes de traitement de déficience cognitive
CN116003404B (zh) *	2022-12-14	2024-10-01	杭州同舟生物技术有限公司	一种利培酮人工半抗原、人工抗原及其制备方法和应用

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4342870A (en) *	1980-03-28	1982-08-03	Janssen Pharmaceutica N.V.	Novel 3-(1-piperidinylalkyl)-4H-pyrido[1,2-a]pyrimidin-4-one derivatives
US4804663A (en) *	1985-03-27	1989-02-14	Janssen Pharmaceutica N.V.	3-piperidinyl-substituted 1,2-benzisoxazoles and 1,2-benzisothiazoles

1989
- 1989-10-16 CA CA002000786A patent/CA2000786C/fr not_active Expired - Lifetime
- 1989-10-18 NZ NZ231062A patent/NZ231062A/xx unknown
- 1989-10-30 DE DE68922577T patent/DE68922577T2/de not_active Expired - Lifetime
- 1989-10-30 DE DE122007000081C patent/DE122007000081I2/de active Active
- 1989-10-30 EP EP89202724A patent/EP0368388B1/fr not_active Expired - Lifetime
- 1989-10-30 AT AT89202724T patent/ATE122349T1/de active
- 1989-10-30 ES ES89202724T patent/ES2075036T3/es not_active Expired - Lifetime
- 1989-10-30 CY CY192689A patent/CY1926A/xx unknown
- 1989-11-03 IL IL92208A patent/IL92208A0/xx not_active IP Right Cessation
- 1989-11-06 IE IE356489A patent/IE66370B1/en not_active IP Right Cessation
- 1989-11-06 FI FI895261A patent/FI92201C/fi active Protection Beyond IP Right Term
- 1989-11-06 ZA ZA898436A patent/ZA898436B/xx unknown
- 1989-11-06 NO NO894411A patent/NO173015C/no not_active IP Right Cessation
- 1989-11-06 DK DK551989A patent/DK169923B1/da not_active IP Right Cessation
- 1989-11-06 PT PT92206A patent/PT92206B/pt not_active IP Right Cessation
- 1989-11-06 AU AU44436/89A patent/AU614437B2/en not_active Expired
- 1989-11-07 JP JP1289842A patent/JP2758045B2/ja not_active Expired - Lifetime
- 1989-11-07 KR KR1019890016114A patent/KR0146053B1/ko not_active Expired - Lifetime
1996
- 1996-07-18 HK HK131696A patent/HK131696A/en not_active IP Right Cessation
2004
- 2004-05-20 CL CL200401183A patent/CL43432B/es active
2007
- 2007-09-12 LU LU91362C patent/LU91362I2/fr unknown
- 2007-10-15 CY CY200700025C patent/CY2007025I2/el unknown
- 2007-10-17 NL NL300298C patent/NL300298I2/nl unknown
- 2007-12-21 NO NO2007017C patent/NO2007017I2/no unknown

Also Published As

Publication number	Publication date
CA2000786A1 (fr)	1990-05-07
CY2007025I1 (el)	2009-11-04
IE66370B1 (en)	1995-12-27
NZ231062A (en)	1991-09-25
IL92208A0 (en)	1990-07-26
NO894411L (no)	1990-05-08
CY1926A (en)	1989-10-30
DK551989D0 (da)	1989-11-06
CA2000786C (fr)	1999-01-26
NO894411D0 (no)	1989-11-06
FI895261A0 (fi)	1989-11-06
FI92201C (fi)	1994-10-10
EP0368388A3 (fr)	1991-07-17
KR0146053B1 (ko)	1998-08-17
JPH02191276A (ja)	1990-07-27
ZA898436B (en)	1991-07-31
EP0368388B1 (fr)	1995-05-10
FI92201B (fi)	1994-06-30
LU91362I2 (fr)	2007-11-12
KR910009700A (ko)	1991-06-28
ES2075036T3 (es)	1995-10-01
DE122007000081I2 (de)	2010-01-28
NL300298I2 (nl)	2008-03-03
NO173015B (no)	1993-07-05
EP0368388A2 (fr)	1990-05-16
NO173015C (no)	1993-10-13
JP2758045B2 (ja)	1998-05-25
DE122007000081I1 (de)	2008-02-28
PT92206B (pt)	1995-07-06
HK131696A (en)	1996-07-26
NO2007017I2 (no)	2010-01-25
AU4443689A (en)	1990-05-10
PT92206A (pt)	1990-05-31
DE68922577T2 (de)	1995-09-28
NO2007017I1 (no)	2008-01-14
NL300298I1 (nl)	2007-12-03
DE68922577D1 (de)	1995-06-14
AU614437B2 (en)	1991-08-29
DK551989A (da)	1990-05-08
ATE122349T1 (de)	1995-05-15
CY2007025I2 (el)	2009-11-04
CL43432B (es)	2005-06-03
IE893564L (en)	1990-05-07

Legal Events

Date	Code	Title	Description
1995-04-03	B1	Patent granted (law 1993)
2008-01-28	CTFF	Application for supplementary protection certificate (spc) filed	Spc suppl protection certif: CA 2007 00071 Filing date: 20071219 Expiry date: 20141106
2008-05-19	CTFG	Supplementary protection certificate (spc) issued	Free format text: PRODUCT NAME: PALIPERIDON ((PLUS MINUS)-3-{2-[4-(6-FLUOR-1,2-BENZISOXAZOL-3-YL)PIPERIDINO]ETHYL}-6,7,8,9-TETRAHYDRO-9-HYDROXY-2-METHYL-4H-PYRIDO[1,2-A]PYRIMIDIN-4-ON) Spc suppl protection certif: CA 2007 00071 Filing date: 20071219
2009-11-23	PUP	Patent expired

Publication	Publication Date	Title
DK169923B1 (da)	1995-04-03	3-[[4-(1,2-benzisoxazol-3-yl)-1-piperidinyl]alkyl]-6,7,8,9-tetrahydro-2-alkyl-4H-pyrido[1,2-a]pyrimidin-4-on-forbindelser, fremgangsmåde til fremstilling deraf og antipsykotiske præparater indeholdende disse
US6320048B1 (en)	2001-11-20	3-piperidinyl-1,2-benzisoxazoles
US5158952A (en)	1992-10-27	3-[2-[4-(6-fluoro-1,2-benzisoxozol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9 tetrahydro-9-hydroxy-2-methyl-4H-pyrido [1,2-a]pyrimidin-4-one, compositions and method of use
ES2759253T3 (es)	2020-05-08	Derivados de imidazol tricíclicos condensados como moduladores de la actividad de TNF
DK168537B1 (da)	1994-04-18	1,2-benzisoxazol-3-yl- og 1,2-benzisothiazol-3-yl-derivater, en fremgangsmåde til fremstilling deraf og farmaceutiske præparater indeholdende sådanne derivater
ES2743208T3 (es)	2020-02-18	Derivados de tetrahidroimidazopiridina como moduladores de la actividad TNF
CA2175372C (fr)	2006-02-21	Nouveaux derives du 9-hydroxy-pyrido[1,2-a]pyrimidine-4-one ether
ES2752144T3 (es)	2020-04-03	Derivados de tetrahidrobencimidazol como moduladores de la actividad de TNF
KR100190297B1 (ko)	1999-06-01	신규 2,9-이치환된-4H-피리도[1,2-a]피리미딘-4-온
WO2009121812A1 (fr)	2009-10-08	Tétrahydronaphthyridines et ses dérivés aza à titre d'antagonistes des récepteurs d'histamine h3
DK175124B1 (da)	2004-06-07	3-piperazinylbenzazolderivater, fremstilling deraf og anvendelse deraf i et antipsykotisk præparat
US5075315A (en)	1991-12-24	Antipsychotic hexahydro-2H-indeno[1,2-c]pyridine derivatives
KR100251892B1 (ko)	2000-09-01	신규한 4-(3-벤조푸라닐)피페리디닐 및 4-(3-벤조티에닐)피페리디닐 유도체 및 이들을 함유하는 약제학적 조성물
HU223466B1 (hu)	2004-07-28	Allergia elleni imidazo[1,2a]tieno[2,3-d]azepin-származékok, eljárás előállításukra és az ezeket tartalmazó gyógyszerkészítmények
HRP950531A2 (en)	1997-10-31	1,2-benzisoxazol-3-yl derivatives