IL92466A - History of arylpifridine and pharmaceutical preparations containing them - Google Patents

History of arylpifridine and pharmaceutical preparations containing them

Info

Publication number: IL92466A
Authority: IL; Israel
Prior art keywords: methoxyphenyl; product; naphthyl; compound; preparation
Prior art date: 1988-12-02

Application number

IL9246689A

Other languages

English (en)

Hebrew (he)

Other versions

IL92466A0 (en

Original Assignee

Pfizer Inc New York N Y

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.)

1988-12-02

Filing date

1989-11-27

Publication date

1994-02-27

1989-11-27 Application filed by Pfizer Inc New York N Y filed Critical Pfizer Inc New York N Y

1990-08-31 Publication of IL92466A0 publication Critical patent/IL92466A0/xx

1994-02-27 Publication of IL92466A publication Critical patent/IL92466A/en

Links

239000008194 pharmaceutical composition Substances 0.000 title claims description 5
-1 trifluoromethylphenyl Chemical group 0.000 claims abstract description 56
125000001624 naphthyl group Chemical group 0.000 claims abstract description 6
125000003944 tolyl group Chemical group 0.000 claims abstract description 6
229910052760 oxygen Inorganic materials 0.000 claims abstract description 5
229910052801 chlorine Inorganic materials 0.000 claims abstract description 4
125000004464 hydroxyphenyl group Chemical group 0.000 claims abstract description 4
125000000068 chlorophenyl group Chemical group 0.000 claims abstract description 3
229910052731 fluorine Inorganic materials 0.000 claims abstract description 3
125000001207 fluorophenyl group Chemical group 0.000 claims abstract description 3
229910052717 sulfur Inorganic materials 0.000 claims abstract description 3
150000001875 compounds Chemical class 0.000 claims description 47
125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 14
239000002253 acid Substances 0.000 claims description 14
150000003839 salts Chemical class 0.000 claims description 14
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 11
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
230000000561 anti-psychotic effect Effects 0.000 claims description 5
239000003085 diluting agent Substances 0.000 claims description 5
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
239000001301 oxygen Substances 0.000 claims description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
239000000460 chlorine Chemical group 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
239000011737 fluorine Substances 0.000 claims description 2
125000001153 fluoro group Chemical group F* 0.000 claims description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
238000007911 parenteral administration Methods 0.000 claims description 2
239000011593 sulfur Chemical group 0.000 claims description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
125000003386 piperidinyl group Chemical group 0.000 claims 2
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 abstract description 11
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 abstract description 10
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 abstract description 6
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 abstract description 5
125000005429 oxyalkyl group Chemical group 0.000 abstract description 5
229910000029 sodium carbonate Inorganic materials 0.000 abstract description 5
229910000027 potassium carbonate Inorganic materials 0.000 abstract description 4
150000004820 halides Chemical class 0.000 abstract description 3
239000003495 polar organic solvent Substances 0.000 abstract description 3
125000003710 aryl alkyl group Chemical group 0.000 abstract description 2
125000005160 aryl oxy alkyl group Chemical group 0.000 abstract description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract description 2
229910052736 halogen Inorganic materials 0.000 abstract description 2
150000002367 halogens Chemical class 0.000 abstract description 2
235000015320 potassium carbonate Nutrition 0.000 abstract 1
235000017550 sodium carbonate Nutrition 0.000 abstract 1
239000000047 product Substances 0.000 description 86
238000005481 NMR spectroscopy Methods 0.000 description 63
238000002360 preparation method Methods 0.000 description 57
238000001819 mass spectrum Methods 0.000 description 37
238000000034 method Methods 0.000 description 37
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
239000002585 base Substances 0.000 description 27
239000012467 final product Substances 0.000 description 27
239000007858 starting material Substances 0.000 description 26
238000006243 chemical reaction Methods 0.000 description 24
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 18
239000011541 reaction mixture Substances 0.000 description 17
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
239000000243 solution Substances 0.000 description 12
239000000203 mixture Substances 0.000 description 10
208000028017 Psychotic disease Diseases 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
239000003921 oil Substances 0.000 description 9
235000019198 oils Nutrition 0.000 description 9
239000002904 solvent Substances 0.000 description 8
XINQFOMFQFGGCQ-UHFFFAOYSA-L (2-dodecoxy-2-oxoethyl)-[6-[(2-dodecoxy-2-oxoethyl)-dimethylazaniumyl]hexyl]-dimethylazanium;dichloride Chemical compound [Cl-].[Cl-].CCCCCCCCCCCCOC(=O)C[N+](C)(C)CCCCCC[N+](C)(C)CC(=O)OCCCCCCCCCCCC XINQFOMFQFGGCQ-UHFFFAOYSA-L 0.000 description 7
239000000463 material Substances 0.000 description 7
238000012360 testing method Methods 0.000 description 7
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
238000001704 evaporation Methods 0.000 description 6
230000008020 evaporation Effects 0.000 description 6
238000001914 filtration Methods 0.000 description 6
238000010992 reflux Methods 0.000 description 6
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
238000003756 stirring Methods 0.000 description 6
AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 6
241001465754 Metazoa Species 0.000 description 5
241000700159 Rattus Species 0.000 description 5
239000002274 desiccant Substances 0.000 description 5
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
239000003176 neuroleptic agent Substances 0.000 description 5
DLKQHBOKULLWDQ-UHFFFAOYSA-N 1-bromonaphthalene Chemical compound C1=CC=C2C(Br)=CC=CC2=C1 DLKQHBOKULLWDQ-UHFFFAOYSA-N 0.000 description 4
AFHWNVZETLZAGN-UHFFFAOYSA-N 3-(2-methoxyphenyl)piperidine Chemical compound COC1=CC=CC=C1C1CNCCC1 AFHWNVZETLZAGN-UHFFFAOYSA-N 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
FVIGODVHAVLZOO-UHFFFAOYSA-N Dixanthogen Chemical compound CCOC(=S)SSC(=S)OCC FVIGODVHAVLZOO-UHFFFAOYSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-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
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
239000007984 Tris EDTA buffer Substances 0.000 description 4
239000000164 antipsychotic agent Substances 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
239000007788 liquid Substances 0.000 description 4
GJYXGIIWJFZCLN-UHFFFAOYSA-N octane-2,4-dione Chemical compound CCCCC(=O)CC(C)=O GJYXGIIWJFZCLN-UHFFFAOYSA-N 0.000 description 4
239000000376 reactant Substances 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
LFTGLYCNMGGMKL-UHFFFAOYSA-N 3-(2-chloroethyl)-2-methylpyrido[1,2-a]pyrimidin-4-one Chemical compound C1=CC=CN2C(=O)C(CCCl)=C(C)N=C21 LFTGLYCNMGGMKL-UHFFFAOYSA-N 0.000 description 3
WFIGZOLXTMXGGX-UHFFFAOYSA-N 3-naphthalen-1-ylpiperidine Chemical compound C1CCNCC1C1=CC=CC2=CC=CC=C12 WFIGZOLXTMXGGX-UHFFFAOYSA-N 0.000 description 3
FGJPOWBNULYFQN-UHFFFAOYSA-N 4-[4-(2-chloroethyl)phenyl]-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C=CC(CCCl)=CC=2)=C1 FGJPOWBNULYFQN-UHFFFAOYSA-N 0.000 description 3
SSSBLYQLIOQJSB-UHFFFAOYSA-N 4-naphthalen-1-ylpiperidine Chemical compound C1CNCCC1C1=CC=CC2=CC=CC=C12 SSSBLYQLIOQJSB-UHFFFAOYSA-N 0.000 description 3
HPXJIGZLXHQSGU-UHFFFAOYSA-N 5-(2-chloroethyl)-1,3-dihydroindol-2-one Chemical compound ClCCC1=CC=C2NC(=O)CC2=C1 HPXJIGZLXHQSGU-UHFFFAOYSA-N 0.000 description 3
QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
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 3
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
PCKPVGOLPKLUHR-UHFFFAOYSA-N OH-Indolxyl Natural products C1=CC=C2C(O)=CNC2=C1 PCKPVGOLPKLUHR-UHFFFAOYSA-N 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
239000007900 aqueous suspension Substances 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
239000006227 byproduct Substances 0.000 description 3
230000000694 effects Effects 0.000 description 3
239000002024 ethyl acetate extract Substances 0.000 description 3
238000011534 incubation Methods 0.000 description 3
239000012299 nitrogen atmosphere Substances 0.000 description 3
239000008188 pellet Substances 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
238000000159 protein binding assay Methods 0.000 description 3
238000000967 suction filtration Methods 0.000 description 3
HTDQSWDEWGSAMN-UHFFFAOYSA-N 1-bromo-2-methoxybenzene Chemical compound COC1=CC=CC=C1Br HTDQSWDEWGSAMN-UHFFFAOYSA-N 0.000 description 2
125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 2
GSJKJPRTYNBOKU-UHFFFAOYSA-N 4-(2-chloroethyl)phenol Chemical compound OC1=CC=C(CCCl)C=C1 GSJKJPRTYNBOKU-UHFFFAOYSA-N 0.000 description 2
SRAVSVBVHDLLPO-UHFFFAOYSA-N 4-(2-methoxyphenyl)piperidine Chemical compound COC1=CC=CC=C1C1CCNCC1 SRAVSVBVHDLLPO-UHFFFAOYSA-N 0.000 description 2
IPKSNWXGEIHOMR-UHFFFAOYSA-N 4-[3-(trifluoromethyl)phenyl]piperidine Chemical compound FC(F)(F)C1=CC=CC(C2CCNCC2)=C1 IPKSNWXGEIHOMR-UHFFFAOYSA-N 0.000 description 2
WXJWBEAGVWVEDM-UHFFFAOYSA-N 5-(2-chloroacetyl)-1,3-dihydroindol-2-one Chemical compound ClCC(=O)C1=CC=C2NC(=O)CC2=C1 WXJWBEAGVWVEDM-UHFFFAOYSA-N 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
208000009132 Catalepsy Diseases 0.000 description 2
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
241000124008 Mammalia Species 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
229910019142 PO4 Inorganic materials 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
206010047853 Waxy flexibility Diseases 0.000 description 2
125000000217 alkyl group Chemical group 0.000 description 2
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
239000005557 antagonist Substances 0.000 description 2
125000003118 aryl group Chemical group 0.000 description 2
230000027455 binding Effects 0.000 description 2
210000004556 brain Anatomy 0.000 description 2
239000012267 brine Substances 0.000 description 2
239000000872 buffer Substances 0.000 description 2
239000000969 carrier Substances 0.000 description 2
239000012043 crude product Substances 0.000 description 2
238000010908 decantation Methods 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
238000001035 drying Methods 0.000 description 2
229960001484 edetic acid Drugs 0.000 description 2
239000000284 extract Substances 0.000 description 2
239000000945 filler Substances 0.000 description 2
239000012458 free base Substances 0.000 description 2
229940095895 haldol Drugs 0.000 description 2
LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 2
125000000623 heterocyclic group Chemical group 0.000 description 2
JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 description 2
PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 2
YECIFGHRMFEPJK-UHFFFAOYSA-N lidocaine hydrochloride monohydrate Chemical compound O.[Cl-].CC[NH+](CC)CC(=O)NC1=C(C)C=CC=C1C YECIFGHRMFEPJK-UHFFFAOYSA-N 0.000 description 2
238000005567 liquid scintillation counting Methods 0.000 description 2
239000011777 magnesium Substances 0.000 description 2
229910052749 magnesium Inorganic materials 0.000 description 2
239000002609 medium Substances 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
239000010452 phosphate Substances 0.000 description 2
230000035484 reaction time Effects 0.000 description 2
235000009518 sodium iodide Nutrition 0.000 description 2
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
239000007787 solid Substances 0.000 description 2
239000008107 starch Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
239000000126 substance Substances 0.000 description 2
239000006228 supernatant Substances 0.000 description 2
239000000725 suspension Substances 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
239000003826 tablet Substances 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
238000002560 therapeutic procedure 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
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
ZZJYIKPMDIWRSN-TZBSWOFLSA-N (+)-butaclamol Chemical compound C12=CC=CC=C2CCC2=CC=CC3=C2[C@@H]1CN1CC[C@@](C(C)(C)C)(O)C[C@@H]13 ZZJYIKPMDIWRSN-TZBSWOFLSA-N 0.000 description 1
PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
DRCVRXJYMIOWDD-UHFFFAOYSA-N 1-benzyl-4-naphthalen-1-ylpiperidin-4-ol Chemical compound C1CC(O)(C=2C3=CC=CC=C3C=CC=2)CCN1CC1=CC=CC=C1 DRCVRXJYMIOWDD-UHFFFAOYSA-N 0.000 description 1
VQUYNUJARXBNPK-UHFFFAOYSA-N 2-chloroethoxybenzene Chemical compound ClCCOC1=CC=CC=C1 VQUYNUJARXBNPK-UHFFFAOYSA-N 0.000 description 1
ALKYHXVLJMQRLQ-UHFFFAOYSA-N 3-Hydroxy-2-naphthoate Chemical compound C1=CC=C2C=C(O)C(C(=O)O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
UPMLOUAZCHDJJD-UHFFFAOYSA-N 4,4'-Diphenylmethane Diisocyanate Chemical compound C1=CC(N=C=O)=CC=C1CC1=CC=C(N=C=O)C=C1 UPMLOUAZCHDJJD-UHFFFAOYSA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
YDVPYEBAOMTJDM-UHFFFAOYSA-N 4-[2-(4-chlorobutyl)phenyl]-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C(=CC=CC=2)CCCCCl)=C1 YDVPYEBAOMTJDM-UHFFFAOYSA-N 0.000 description 1
LGMRHDKFEPZECY-UHFFFAOYSA-N 4-[2-(4-phenylpiperidin-1-yl)ethyl]phenol Chemical compound C1=CC(O)=CC=C1CCN1CCC(C=2C=CC=CC=2)CC1 LGMRHDKFEPZECY-UHFFFAOYSA-N 0.000 description 1
BLFRQYKZFKYQLO-UHFFFAOYSA-O 4-hydroxybutan-1-aminium Chemical compound [NH3+]CCCCO BLFRQYKZFKYQLO-UHFFFAOYSA-O 0.000 description 1
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UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
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150000004760 silicates Chemical class 0.000 description 1
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NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
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KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
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229960000281 trometamol Drugs 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/20—Spiro-condensed ring 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
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
- C07D211/14—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/22—Bridged ring systems
- C07D221/24—Camphidines
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- 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
- C07D417/10—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 aromatic rings
- 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

Landscapes

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

IL9246689A 1988-12-02 1989-11-27 History of arylpifridine and pharmaceutical preparations containing them IL92466A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
PCT/US1988/004300 WO1990006303A1 (en)	1988-12-02	1988-12-02	Arylpiperidine derivatives

Publications (2)

Publication Number	Publication Date
IL92466A0 IL92466A0 (en)	1990-08-31
IL92466A true IL92466A (en)	1994-02-27

Family

ID=22209025

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL9246689A IL92466A (en)	1988-12-02	1989-11-27	History of arylpifridine and pharmaceutical preparations containing them

Country Status (20)

Country	Link
US (2)	US5153206A (de)
EP (1)	EP0372776B1 (de)
JP (1)	JPH0710850B2 (de)
KR (1)	KR910006980B1 (de)
AT (1)	ATE143366T1 (de)
AU (1)	AU633858B2 (de)
CA (1)	CA2004249C (de)
DE (1)	DE68927254T2 (de)
DK (1)	DK606889A (de)
ES (1)	ES2092475T3 (de)
FI (1)	FI95465C (de)
GR (1)	GR3021496T3 (de)
HU (1)	HU207310B (de)
IE (1)	IE75359B1 (de)
IL (1)	IL92466A (de)
NO (1)	NO175257C (de)
NZ (1)	NZ231612A (de)
PT (1)	PT92468B (de)
WO (1)	WO1990006303A1 (de)
ZA (1)	ZA899192B (de)

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JP6594351B2 (ja)	2014-06-16	2019-10-23	ジョンソン、マッセイ、パブリック、リミテッド、カンパニー	新規中間体を含むアルキル化アリールピペラジン及びアルキル化アリールピペリジン化合物の製造方法
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1988
- 1988-12-02 WO PCT/US1988/004300 patent/WO1990006303A1/en not_active Ceased
- 1988-12-02 US US07/566,435 patent/US5153206A/en not_active Expired - Lifetime
- 1988-12-02 HU HU892324A patent/HU207310B/hu not_active IP Right Cessation
1989
- 1989-11-27 EP EP89312269A patent/EP0372776B1/de not_active Expired - Lifetime
- 1989-11-27 IL IL9246689A patent/IL92466A/en not_active IP Right Cessation
- 1989-11-27 ES ES89312269T patent/ES2092475T3/es not_active Expired - Lifetime
- 1989-11-27 AT AT89312269T patent/ATE143366T1/de not_active IP Right Cessation
- 1989-11-27 DE DE68927254T patent/DE68927254T2/de not_active Expired - Fee Related
- 1989-11-30 JP JP1312235A patent/JPH0710850B2/ja not_active Expired - Lifetime
- 1989-11-30 IE IE381389A patent/IE75359B1/en not_active IP Right Cessation
- 1989-11-30 CA CA002004249A patent/CA2004249C/en not_active Expired - Fee Related
- 1989-11-30 PT PT92468A patent/PT92468B/pt not_active IP Right Cessation
- 1989-12-01 NZ NZ231612A patent/NZ231612A/xx unknown
- 1989-12-01 DK DK606889A patent/DK606889A/da not_active Application Discontinuation
- 1989-12-01 ZA ZA899192A patent/ZA899192B/xx unknown
- 1989-12-01 KR KR1019890017770A patent/KR910006980B1/ko not_active Expired
- 1989-12-04 AU AU45869/89A patent/AU633858B2/en not_active Ceased
1990
- 1990-08-01 NO NO903383A patent/NO175257C/no unknown
- 1990-08-01 FI FI903829A patent/FI95465C/fi not_active IP Right Cessation
1992
- 1992-07-29 US US07/921,878 patent/US5294619A/en not_active Expired - Lifetime
1996
- 1996-10-30 GR GR960402865T patent/GR3021496T3/el unknown

Also Published As

Publication number	Publication date
EP0372776A3 (de)	1991-10-23
DK606889A (da)	1990-07-18
EP0372776B1 (de)	1996-09-25
IL92466A0 (en)	1990-08-31
WO1990006303A1 (en)	1990-06-14
IE893813L (en)	1990-06-02
JPH02275853A (ja)	1990-11-09
AU4586989A (en)	1990-06-28
ES2092475T3 (es)	1996-12-01
FI95465C (fi)	1996-02-12
NZ231612A (en)	1991-02-26
DE68927254T2 (de)	1997-02-06
NO903383L (no)	1990-10-01
FI95465B (fi)	1995-10-31
ATE143366T1 (de)	1996-10-15
KR910011783A (ko)	1991-08-07
NO175257B (no)	1994-06-13
PT92468B (pt)	1995-07-18
JPH0710850B2 (ja)	1995-02-08
US5294619A (en)	1994-03-15
HU207310B (en)	1993-03-29
HU892324D0 (en)	1990-12-28
DK606889D0 (da)	1989-12-01
ZA899192B (en)	1991-07-31
CA2004249A1 (en)	1990-06-02
IE75359B1 (en)	1997-08-27
HUT59127A (en)	1992-04-28
AU633858B2 (en)	1993-02-11
PT92468A (pt)	1990-06-29
NO175257C (no)	1994-09-21
EP0372776A2 (de)	1990-06-13
GR3021496T3 (en)	1997-01-31
NO903383D0 (no)	1990-08-01
FI903829A0 (fi)	1990-08-01
CA2004249C (en)	1996-09-17
US5153206A (en)	1992-10-06
KR910006980B1 (ko)	1991-09-14
DE68927254D1 (de)	1996-10-31

Legal Events

Date	Code	Title	Description
2000-08-31	RH	Patent void

Publication	Publication Date	Title
EP0372776B1 (de)	1996-09-25	Arylpiperidin-Derivate
US5821248A (en)	1998-10-13	Quinuclidine derivatives
AU648317B2 (en)	1994-04-21	3-amino-2-aryl quinuclidines, process for their preparation and pharmaceutical compositions containing them
JP3042894B2 (ja)	2000-05-22	サブスタンスｐアンタゴニストとしての置換ベンゾラクタム化合物
CZ59394A3 (en)	1994-11-16	Condensed tricyclic heterocycles containing nitrogen as antagonists of p substance receptor, process of their preparation, intermediates, pharmaceutical preparations in which they are comprised and use
EP0364091B1 (de)	1993-07-28	Verbrückte bicyclische 4-(4-(3-Benzisothiazolyl)-1-piperazinyl)-butylimide mit antipsychotischer Wirkung
US5109006A (en)	1992-04-28	Certain pharmaceutically active 6H-imidazo[1,2-a]pyridine-5-ones