IL94357A - History of 2-piperidino-1-alkanol and pharmaceuticals containing them - Google Patents

History of 2-piperidino-1-alkanol and pharmaceuticals containing them

Info

Publication number: IL94357A
Authority: IL; Israel
Prior art keywords: mmol; ethyl acetate; title product; ethanol; hydroxy
Prior art date: 1989-05-17

Application number

IL9435790A

Other languages

English (en)

Hebrew (he)

Original Assignee

Pfizer

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1989-05-17

Filing date

1990-05-10

Publication date

1996-08-04

1990-05-10 Application filed by Pfizer filed Critical Pfizer

1990-05-10 Priority to IL11417490A priority Critical patent/IL114174A/en

1996-08-04 Publication of IL94357A publication Critical patent/IL94357A/en

Links

239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 6
150000001875 compounds Chemical class 0.000 claims abstract description 42
238000002360 preparation method Methods 0.000 claims abstract description 30
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 11
239000001257 hydrogen Substances 0.000 claims abstract description 11
125000000217 alkyl group Chemical group 0.000 claims abstract description 7
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 5
125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
150000003839 salts Chemical class 0.000 claims description 12
239000002253 acid Substances 0.000 claims description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
239000003814 drug Substances 0.000 claims description 5
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
125000001475 halogen functional group Chemical group 0.000 claims description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims 1
125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
125000001424 substituent group Chemical group 0.000 claims 1
238000000034 method Methods 0.000 abstract description 49
239000000543 intermediate Substances 0.000 abstract description 9
239000004593 Epoxy Substances 0.000 abstract 1
125000003342 alkenyl group Chemical group 0.000 abstract 1
125000000304 alkynyl group Chemical group 0.000 abstract 1
125000003710 aryl alkyl group Chemical group 0.000 abstract 1
125000003118 aryl group Chemical group 0.000 abstract 1
125000000958 aryl methylene group Chemical group 0.000 abstract 1
125000005110 aryl thio group Chemical group 0.000 abstract 1
125000004104 aryloxy group Chemical group 0.000 abstract 1
208000015114 central nervous system disease Diseases 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 186
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 133
239000000047 product Substances 0.000 description 121
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 81
229940093499 ethyl acetate Drugs 0.000 description 62
235000019439 ethyl acetate Nutrition 0.000 description 62
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 60
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 50
238000005481 NMR spectroscopy Methods 0.000 description 45
238000006243 chemical reaction Methods 0.000 description 41
239000000203 mixture Substances 0.000 description 41
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 32
239000007787 solid Substances 0.000 description 28
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
239000000741 silica gel Substances 0.000 description 25
229910002027 silica gel Inorganic materials 0.000 description 25
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 25
-1 erythro compound Chemical class 0.000 description 23
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
239000003921 oil Substances 0.000 description 22
235000019198 oils Nutrition 0.000 description 22
238000010828 elution Methods 0.000 description 20
239000000243 solution Substances 0.000 description 19
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 17
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
238000003818 flash chromatography Methods 0.000 description 15
239000012267 brine Substances 0.000 description 14
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical group CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 14
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
229940044613 1-propanol Drugs 0.000 description 13
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
150000002576 ketones Chemical class 0.000 description 11
239000002904 solvent Substances 0.000 description 11
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
239000000706 filtrate Substances 0.000 description 9
238000003756 stirring Methods 0.000 description 9
239000005909 Kieselgur Substances 0.000 description 8
239000012442 inert solvent Substances 0.000 description 8
239000012044 organic layer Substances 0.000 description 8
150000002924 oxiranes Chemical class 0.000 description 8
239000012071 phase Substances 0.000 description 8
125000006239 protecting group Chemical group 0.000 description 7
229920006395 saturated elastomer Polymers 0.000 description 7
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
238000004587 chromatography analysis Methods 0.000 description 6
230000000324 neuroprotective effect Effects 0.000 description 6
238000010992 reflux Methods 0.000 description 6
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 6
ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 5
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
229910021529 ammonia Inorganic materials 0.000 description 5
230000002253 anti-ischaemic effect Effects 0.000 description 5
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
229910052794 bromium Inorganic materials 0.000 description 5
ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 5
238000001914 filtration Methods 0.000 description 5
239000007858 starting material Substances 0.000 description 5
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 4
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 4
OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 4
210000003169 central nervous system Anatomy 0.000 description 4
210000001638 cerebellum Anatomy 0.000 description 4
239000012230 colorless oil Substances 0.000 description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 4
239000010410 layer Substances 0.000 description 4
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
230000000269 nucleophilic effect Effects 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
239000011734 sodium Substances 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
208000024827 Alzheimer disease Diseases 0.000 description 3
102000015404 Amino Acid Receptors Human genes 0.000 description 3
108010025177 Amino Acid Receptors Proteins 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
208000023105 Huntington disease Diseases 0.000 description 3
235000019502 Orange oil Nutrition 0.000 description 3
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
208000018737 Parkinson disease Diseases 0.000 description 3
208000006011 Stroke Diseases 0.000 description 3
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
230000000903 blocking effect Effects 0.000 description 3
238000009835 boiling Methods 0.000 description 3
239000007853 buffer solution Substances 0.000 description 3
229910052799 carbon Inorganic materials 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
239000003085 diluting agent Substances 0.000 description 3
208000035475 disorder Diseases 0.000 description 3
238000006073 displacement reaction Methods 0.000 description 3
230000001077 hypotensive effect Effects 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
239000007788 liquid Substances 0.000 description 3
239000000463 material Substances 0.000 description 3
TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 3
239000010502 orange oil Substances 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
239000000725 suspension Substances 0.000 description 3
238000001665 trituration Methods 0.000 description 3
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
FLAYZKKEOIAALB-UHFFFAOYSA-N 2-bromo-1-(4-chlorophenyl)ethanone Chemical compound ClC1=CC=C(C(=O)CBr)C=C1 FLAYZKKEOIAALB-UHFFFAOYSA-N 0.000 description 2
UYNVMODNBIQBMV-UHFFFAOYSA-N 4-[1-hydroxy-2-[4-(phenylmethyl)-1-piperidinyl]propyl]phenol Chemical compound C1CC(CC=2C=CC=CC=2)CCN1C(C)C(O)C1=CC=C(O)C=C1 UYNVMODNBIQBMV-UHFFFAOYSA-N 0.000 description 2
KJZBZOFESQSBCV-UHFFFAOYSA-N 4-benzylpiperidin-4-ol Chemical compound C=1C=CC=CC=1CC1(O)CCNCC1 KJZBZOFESQSBCV-UHFFFAOYSA-N 0.000 description 2
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
XLYOFNOQVPJJNP-ZSJDYOACSA-N Heavy water Chemical compound [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical class [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 2
241000124008 Mammalia Species 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
241000700159 Rattus Species 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
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 2
JDDPSVBBPCQWAL-JVHMLUBASA-N [(1s,5r)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] methanesulfonate Chemical compound C1C(OS(C)(=O)=O)C[C@H]2CC[C@@H]1N2C JDDPSVBBPCQWAL-JVHMLUBASA-N 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
235000019270 ammonium chloride Nutrition 0.000 description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
239000002585 base Substances 0.000 description 2
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
230000005587 bubbling Effects 0.000 description 2
239000000872 buffer Substances 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
125000001309 chloro group Chemical group Cl* 0.000 description 2
KQIADDMXRMTWHZ-UHFFFAOYSA-N chloro-tri(propan-2-yl)silane Chemical compound CC(C)[Si](Cl)(C(C)C)C(C)C KQIADDMXRMTWHZ-UHFFFAOYSA-N 0.000 description 2
238000004821 distillation Methods 0.000 description 2
238000006735 epoxidation reaction Methods 0.000 description 2
125000004185 ester group Chemical group 0.000 description 2
238000001640 fractional crystallisation Methods 0.000 description 2
239000007789 gas Substances 0.000 description 2
125000005843 halogen group Chemical group 0.000 description 2
150000003840 hydrochlorides Chemical class 0.000 description 2
229960003998 ifenprodil Drugs 0.000 description 2
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
150000004682 monohydrates Chemical class 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
239000002674 ointment Substances 0.000 description 2
239000001301 oxygen Substances 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
RARSHUDCJQSEFJ-UHFFFAOYSA-N p-Hydroxypropiophenone Chemical compound CCC(=O)C1=CC=C(O)C=C1 RARSHUDCJQSEFJ-UHFFFAOYSA-N 0.000 description 2
DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 2
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
150000003053 piperidines Chemical class 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
239000000843 powder Substances 0.000 description 2
235000018102 proteins Nutrition 0.000 description 2
108090000623 proteins and genes Proteins 0.000 description 2
102000004169 proteins and genes Human genes 0.000 description 2
238000000746 purification Methods 0.000 description 2
238000000526 short-path distillation Methods 0.000 description 2
239000002002 slurry Substances 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
239000012265 solid product Substances 0.000 description 2
230000009466 transformation Effects 0.000 description 2
238000000844 transformation Methods 0.000 description 2
IBWLXNDOMYKTAD-QMMMGPOBSA-N (2r)-2-(4-chlorophenyl)oxirane Chemical compound C1=CC(Cl)=CC=C1[C@H]1OC1 IBWLXNDOMYKTAD-QMMMGPOBSA-N 0.000 description 1
XGUPAUDEUUVJJO-UHFFFAOYSA-N 1-(2-hydroxy-2-thiophen-2-ylethyl)-4-phenylpiperidin-4-ol Chemical compound C=1C=CSC=1C(O)CN(CC1)CCC1(O)C1=CC=CC=C1 XGUPAUDEUUVJJO-UHFFFAOYSA-N 0.000 description 1
BPLSNCQUDPGZPD-UHFFFAOYSA-N 1-(3-phenylsulfanyl-8-azabicyclo[3.2.1]octan-8-yl)propan-1-ol Chemical compound CCC(O)N1C(C2)CCC1CC2SC1=CC=CC=C1 BPLSNCQUDPGZPD-UHFFFAOYSA-N 0.000 description 1
QEMSVZNTSXPFJA-BEFAXECRSA-N 1-[(1r,2r)-1-hydroxy-1-(4-hydroxyphenyl)propan-2-yl]-4-phenylpiperidin-4-ol Chemical class C1([C@@H](O)[C@@H](C)N2CCC(O)(CC2)C=2C=CC=CC=2)=CC=C(O)C=C1 QEMSVZNTSXPFJA-BEFAXECRSA-N 0.000 description 1
CBXGLNWPAKZNTA-UHFFFAOYSA-N 1-[2-(4-aminophenyl)-2-hydroxyethyl]-4-phenylpiperidin-4-ol Chemical compound C1=CC(N)=CC=C1C(O)CN1CCC(O)(C=2C=CC=CC=2)CC1 CBXGLNWPAKZNTA-UHFFFAOYSA-N 0.000 description 1
JLRNTPVSALEDDX-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)-2-hydroxyethyl]-4-phenylpiperidin-4-ol Chemical compound C=1C=C(Cl)C=CC=1C(O)CN(CC1)CCC1(O)C1=CC=CC=C1 JLRNTPVSALEDDX-UHFFFAOYSA-N 0.000 description 1
QBAOJIKKBZSGHT-UHFFFAOYSA-N 1-[4-tri(propan-2-yl)silyloxyphenyl]propan-1-ol Chemical compound C(C)(C)[Si](OC1=CC=C(C=C1)C(CC)O)(C(C)C)C(C)C QBAOJIKKBZSGHT-UHFFFAOYSA-N 0.000 description 1
LJCZNYWLQZZIOS-UHFFFAOYSA-N 2,2,2-trichlorethoxycarbonyl chloride Chemical compound ClC(=O)OCC(Cl)(Cl)Cl LJCZNYWLQZZIOS-UHFFFAOYSA-N 0.000 description 1
LECBJEBOKYUBCI-UHFFFAOYSA-N 2,2,2-trichloroethyl 3-phenylsulfanyl-8-azabicyclo[3.2.1]octane-8-carboxylate Chemical compound ClC(Cl)(Cl)COC(=O)N1C(C2)CCC1CC2SC1=CC=CC=C1 LECBJEBOKYUBCI-UHFFFAOYSA-N 0.000 description 1
HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
CJSHUGIPSZMLFH-UHFFFAOYSA-N 2-(3-benzylidene-8-azabicyclo[3.2.1]octan-8-yl)-1-[4-tri(propan-2-yl)silyloxyphenyl]propan-1-one Chemical compound C1=CC(O[Si](C(C)C)(C(C)C)C(C)C)=CC=C1C(=O)C(C)N1C(C2)CCC1CC2=CC1=CC=CC=C1 CJSHUGIPSZMLFH-UHFFFAOYSA-N 0.000 description 1
GQECBCCUCATNEX-UHFFFAOYSA-N 2-(4-benzyl-4-hydroxypiperidin-1-yl)-1-(4-chlorophenyl)ethanone Chemical compound C1CN(CC(=O)C=2C=CC(Cl)=CC=2)CCC1(O)CC1=CC=CC=C1 GQECBCCUCATNEX-UHFFFAOYSA-N 0.000 description 1
SWTHKRSTBWFPDD-UHFFFAOYSA-N 2-(4-benzyl-4-hydroxypiperidin-1-yl)-1-(4-chlorophenyl)propan-1-one Chemical compound C=1C=C(Cl)C=CC=1C(=O)C(C)N(CC1)CCC1(O)CC1=CC=CC=C1 SWTHKRSTBWFPDD-UHFFFAOYSA-N 0.000 description 1
PWSSIXYMTOGFMT-UHFFFAOYSA-N 2-(4-benzyl-4-hydroxypiperidin-1-yl)-1-(4-fluorophenyl)propan-1-one Chemical compound C=1C=C(F)C=CC=1C(=O)C(C)N(CC1)CCC1(O)CC1=CC=CC=C1 PWSSIXYMTOGFMT-UHFFFAOYSA-N 0.000 description 1
IDLUMBHZGJYDAZ-UHFFFAOYSA-N 2-(4-benzyl-4-hydroxypiperidin-1-yl)-1-(4-phenylmethoxyphenyl)propan-1-one Chemical compound C=1C=C(OCC=2C=CC=CC=2)C=CC=1C(=O)C(C)N(CC1)CCC1(O)CC1=CC=CC=C1 IDLUMBHZGJYDAZ-UHFFFAOYSA-N 0.000 description 1
UNRHYKUJRVFZKJ-UHFFFAOYSA-N 2-(4-hydroxy-4-phenylpiperidin-1-yl)-1-[4-tri(propan-2-yl)silyloxyphenyl]propan-1-one Chemical compound C1=CC(O[Si](C(C)C)(C(C)C)C(C)C)=CC=C1C(=O)C(C)N1CCC(O)(C=2C=CC=CC=2)CC1 UNRHYKUJRVFZKJ-UHFFFAOYSA-N 0.000 description 1
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LZHJEBPHIGCFLD-UHFFFAOYSA-N 3-benzylidene-8-azabicyclo[3.2.1]octane Chemical compound C1C(N2)CCC2CC1=CC1=CC=CC=C1 LZHJEBPHIGCFLD-UHFFFAOYSA-N 0.000 description 1
ZRNACQREEIWUAE-UHFFFAOYSA-N 3-phenylsulfanyl-8-azabicyclo[3.2.1]octane Chemical compound C1C(N2)CCC2CC1SC1=CC=CC=C1 ZRNACQREEIWUAE-UHFFFAOYSA-N 0.000 description 1
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KQKFQBTWXOGINC-UHFFFAOYSA-N 4-phenylpiperidin-4-ol Chemical compound C=1C=CC=CC=1C1(O)CCNCC1 KQKFQBTWXOGINC-UHFFFAOYSA-N 0.000 description 1
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VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
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239000006227 byproduct Substances 0.000 description 1
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238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
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239000003257 excitatory amino acid Substances 0.000 description 1
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239000008187 granular material Substances 0.000 description 1
239000012456 homogeneous solution Substances 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
238000007327 hydrogenolysis reaction Methods 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
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125000004356 hydroxy functional group Chemical group O* 0.000 description 1
125000002768 hydroxyalkyl group Chemical group 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
238000011534 incubation Methods 0.000 description 1
238000002329 infrared spectrum Methods 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 1
239000012948 isocyanate Substances 0.000 description 1
150000002513 isocyanates Chemical class 0.000 description 1
239000006210 lotion Substances 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
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IUKIPMYOCFZLFY-UHFFFAOYSA-N methyl 4-[1-hydroxy-2-(4-hydroxy-4-phenylpiperidin-1-yl)ethyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C(O)CN1CCC(O)(C=2C=CC=CC=2)CC1 IUKIPMYOCFZLFY-UHFFFAOYSA-N 0.000 description 1
ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 1
238000002156 mixing Methods 0.000 description 1
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235000019796 monopotassium phosphate Nutrition 0.000 description 1
SKSSZONONLDFBE-UHFFFAOYSA-N n-[4-[1-hydroxy-2-(4-hydroxy-4-phenylpiperidin-1-yl)ethyl]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1C(O)CN1CCC(O)(C=2C=CC=CC=2)CC1 SKSSZONONLDFBE-UHFFFAOYSA-N 0.000 description 1
208000015122 neurodegenerative disease Diseases 0.000 description 1
101150009274 nhr-1 gene Proteins 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
229910000510 noble metal Inorganic materials 0.000 description 1
JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
LWIHDJKSTIGBAC-UHFFFAOYSA-K potassium phosphate Substances [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
239000002243 precursor Substances 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
239000003586 protic polar solvent Substances 0.000 description 1
230000000506 psychotropic effect Effects 0.000 description 1
239000013014 purified material Substances 0.000 description 1
239000000376 reactant Substances 0.000 description 1
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239000000523 sample Substances 0.000 description 1
125000004469 siloxy group Chemical group [SiH3]O* 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
238000000638 solvent extraction Methods 0.000 description 1
239000011550 stock solution Substances 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
125000003396 thiol group Chemical group [H]S* 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
CYHOMWAPJJPNMW-JIGDXULJSA-N tropine Chemical compound C1[C@@H](O)C[C@H]2CC[C@@H]1N2C CYHOMWAPJJPNMW-JIGDXULJSA-N 0.000 description 1
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Classifications

- 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
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- 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
- A61P25/28—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
- 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
- C07D211/36—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/48—Oxygen atoms attached in position 4 having an acyclic carbon atom attached in position 4
- 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
- C07D211/36—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/52—Oxygen atoms attached in position 4 having an aryl radical as the second substituent in position 4
- 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
- C07D211/36—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/54—Sulfur atoms
- 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
- C07D211/68—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 one double bond between ring members or between a ring member and a non-ring member
- C07D211/70—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 one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- 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
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
- C07D451/06—Oxygen atoms

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

IL9435790A 1989-05-17 1990-05-10 History of 2-piperidino-1-alkanol and pharmaceuticals containing them IL94357A (en)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
IL11417490A IL114174A (en)	1989-05-17	1990-05-10	History of 2-piperidino-1-alkanol or alkanone

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
PCT/US1989/002176 WO1990014087A1 (en)	1989-05-17	1989-05-17	2-piperidino-1-alkanol derivatives as antiischemic agents
PCT/US1990/000292 WO1990014088A1 (en)	1989-05-17	1990-01-16	2-piperidino-1-alkanol derivatives as antiischemic agents

Publications (1)

Publication Number	Publication Date
IL94357A true IL94357A (en)	1996-08-04

Family

ID=22215027

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
IL9435790A IL94357A (en)	1989-05-17	1990-05-10	History of 2-piperidino-1-alkanol and pharmaceuticals containing them
IL11417490A IL114174A (en)	1989-05-17	1990-05-10	History of 2-piperidino-1-alkanol or alkanone

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
IL11417490A IL114174A (en)	1989-05-17	1990-05-10	History of 2-piperidino-1-alkanol or alkanone

Country Status (18)

Country	Link
US (3)	US5185343A (pl)
JP (1)	JPH0735368B2 (pl)
KR (1)	KR920004138B1 (pl)
CN (1)	CN1032209C (pl)
AT (1)	ATE150021T1 (pl)
BR (1)	BR1101053A (pl)
CZ (1)	CZ284342B6 (pl)
DE (1)	DE69030134T2 (pl)
DK (1)	DK0398578T3 (pl)
FI (1)	FI113645B (pl)
IL (2)	IL94357A (pl)
NO (1)	NO180268C (pl)
PH (1)	PH31464A (pl)
PL (1)	PL163580B1 (pl)
RU (1)	RU2029769C1 (pl)
SK (1)	SK279476B6 (pl)
WO (2)	WO1990014087A1 (pl)
ZA (1)	ZA903741B (pl)

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FI934566L (fi) *	1991-04-18	1993-10-15	Pfizer	Prodrug-estrar av fenol-2-piperidino-1-alkanoler
US5594007A (en) *	1991-04-18	1997-01-14	Pfizer Inc.	Method for treating spinal cord trauma with phenolic 2-piperidino-1-alkanols
US5710168A (en) *	1991-10-23	1998-01-20	Pfizer Inc.	2-piperidino-1-alkanol derivatives as neuroprotective agents
US6255322B1 (en) *	1992-06-19	2001-07-03	Pfizer Inc.	2-(4-hydroxypiperidino)-1-alkanol derivatives as antiischemic agents
US5436255A (en) *	1992-07-23	1995-07-25	Pfizer Inc.	Method of treating diseases susceptable to treatment by blocking NMDA-receptors
US5498610A (en) *	1992-11-06	1996-03-12	Pfizer Inc.	Neuroprotective indolone and related derivatives
BR9408506A (pt) *	1994-01-31	1997-08-05	Pfizer	Compostos neuroprotetores
RU2139857C1 (ru) *	1994-08-18	1999-10-20	Пфайзер Инк.	Производные 3-(пиперидинил-1)-хроман-4,7-диола и 1-(4-гидроксифенил)-2-(пиперидинил-1)-алканола, фармацевтическая композиция и способ связывания nmda рецептора
US5731317A (en) *	1995-03-10	1998-03-24	Merck & Co., Inc.	Bridged piperidines promote release of growth hormone
IL122649A (en) *	1995-08-11	2001-08-26	Pfizer	(1s, 2s) - 1- (4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidin-1-yl)-1-propanol methanesulfonate trihydrate, its use in the preparation of medicaments and pharmaceutical compositions comprising same
TW450807B (en) *	1995-09-15	2001-08-21	Pfizer	Pharmaceutical compositions for treating tinnitus comprising neuroprotective agents
GB9726569D0 (en) *	1997-12-16	1998-02-11	Univ Southampton	Neuroprotective agents
US5985936A (en) *	1997-12-18	1999-11-16	Forbes Medi-Tech, Inc.	Method of preventing and delaying onset of Alzheimer's disease and composition therefor
NZ503809A (en) *	1997-12-19	2002-04-26	Schering Ag	Ortho-anthranilamide derivatives as anti-coagulants
EP1186303A3 (en) *	2000-09-06	2003-12-10	Pfizer Products Inc.	Pharmaceutical combinations, for the treatment of stroke and traumatic brain injury, containing a neutrophil inhibiting factor and an selective NMDA-NR2B receptor antagonist
IL145209A0 (en) *	2000-09-06	2002-06-30	Pfizer Prod Inc	Pharmaceutical combinations for the treatment of stroke and traumatic brain injury
EP1674087A1 (en)	2000-10-02	2006-06-28	Pfizer Products Inc.	Prophylactic use of n-methyl-d-aspartate (NMDA) antagonists
KR100890676B1 (ko)	2001-07-24	2009-03-26	리히데 게데온 베기에스제티 기아르 알티	신규한 카르복시산 아미드 화합물
EP1666464A4 (en) *	2003-09-25	2008-12-10	Shionogi & Co	PIPERIDINE DERIVATIVE HAVING ANTAGONIST ACTIVITY OF THE NDMA RECEPTOR
CA2547283C (en) *	2003-11-26	2010-11-09	Pfizer Products Inc.	Aminopyrazole derivatives as gsk-3 inhibitors
EP1838705A2 (en) *	2005-01-13	2007-10-03	Neurosearch A/S	3,8-substituted 8-aza-bicyclo [3.2.1] octane derivatives and their use as monoamine neurotransmitter re-uptake inhibitors
FR2919353B1 (fr)	2007-07-23	2014-02-14	Alstom Power Hydraulique	Machine hydraulique comprenant des moyens d'injection d'un ecoulement preleve d'un ecoulement principal
US8648198B2 (en)	2011-01-19	2014-02-11	Cold Spring Harbor Laboratory	Phenylethanolamine-based NMDA receptor antagonists
SG10201800159QA (en)	2011-11-22	2018-02-27	Univ California	Cysteamine and/or cystamine for treating ischemic injury

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB963639A (en) *	1960-10-20	1964-07-15	Arnold Heyworth Beckett	New piperidine derivatives and processes for preparing the same
US3294804A (en) *	1961-01-27	1966-12-27	Sterling Drug Inc	1-(3-hydroxy-3-phenylpropyl)-4-phenyl-4-propionoxy-piperidine
US3136778A (en) *	1961-02-27	1964-06-09	Parke Davis & Co	1-[(omega oxy-lower alkyl)]-2-methyl-3-phenyl-3-propionyloxy-pyrrolidines
BE615410A (pl) *	1961-03-22
FR5733M (pl) *	1966-09-27	1968-01-22
JPS532474A (en) *	1976-06-26	1978-01-11	Yoshitomi Pharmaceut Ind Ltd	Aminoketone derivatives
JPS5359675A (en) *	1976-11-08	1978-05-29	Yoshitomi Pharmaceut Ind Ltd	Aminoalcohol derivatives
DE3045688A1 (de) *	1980-12-04	1982-07-08	C.H. Boehringer Sohn, 6507 Ingelheim	Neue 8-arylalkyl-3-phenyl-3-nortropanole, deren saeureadditionssalze, diese enthaltende arzneimittel und verfahren zu ihrer herstellung
US4366154A (en) *	1981-11-09	1982-12-28	Sandoz, Inc.	Tropyl derivatives
FR2546166B1 (fr) *	1983-05-19	1985-10-25	Synthelabo	Enantiomeres du erythro (benzyl-4 piperidino)-2 (hydroxy-4 ou benzyloxy-4 phenyl)-1 propanol, leur preparation et leur application en therapeutique
JPS60228460A (ja) *	1984-04-27	1985-11-13	Nippon Iyakuhin Kogyo Kk	ピペリジノプロパノ−ル誘導体の製法
JPS6136262A (ja) *	1984-07-26	1986-02-20	Nippon Iyakuhin Kogyo Kk	ピペリジノ−プロパノンもしくは−プロパノール誘導体及びその製法

1989
- 1989-05-17 WO PCT/US1989/002176 patent/WO1990014087A1/en not_active Ceased
- 1989-05-17 SK SK2328-90A patent/SK279476B6/sk unknown
1990
- 1990-01-16 WO PCT/US1990/000292 patent/WO1990014088A1/en not_active Ceased
- 1990-01-16 US US07/784,446 patent/US5185343A/en not_active Expired - Lifetime
- 1990-05-09 DE DE69030134T patent/DE69030134T2/de not_active Expired - Lifetime
- 1990-05-09 AT AT90304975T patent/ATE150021T1/de not_active IP Right Cessation
- 1990-05-09 DK DK90304975.7T patent/DK0398578T3/da active
- 1990-05-10 IL IL9435790A patent/IL94357A/en not_active IP Right Cessation
- 1990-05-10 IL IL11417490A patent/IL114174A/en not_active IP Right Cessation
- 1990-05-11 CZ CS902328A patent/CZ284342B6/cs not_active IP Right Cessation
- 1990-05-15 PL PL90285190A patent/PL163580B1/pl not_active IP Right Cessation
- 1990-05-16 KR KR1019900006989A patent/KR920004138B1/ko not_active Expired
- 1990-05-16 CN CN90103712A patent/CN1032209C/zh not_active Expired - Fee Related
- 1990-05-16 ZA ZA903741A patent/ZA903741B/xx unknown
- 1990-05-16 PH PH40525A patent/PH31464A/en unknown
- 1990-05-17 JP JP2128116A patent/JPH0735368B2/ja not_active Expired - Lifetime
1991
- 1991-11-15 RU SU915010430A patent/RU2029769C1/ru not_active IP Right Cessation
- 1991-11-15 FI FI915403A patent/FI113645B/fi active
- 1991-11-15 NO NO914485A patent/NO180268C/no unknown
1993
- 1993-07-23 US US08/096,913 patent/US5338754A/en not_active Expired - Lifetime
1994
- 1994-04-15 US US08/228,466 patent/US5391742A/en not_active Expired - Lifetime
1997
- 1997-05-14 BR BR1101053-3A patent/BR1101053A/pt active IP Right Grant

Also Published As

Publication number	Publication date
KR900018085A (ko)	1990-12-20
HK1000468A1 (en)	1998-03-27
FI113645B (fi)	2004-05-31
JPH035478A (ja)	1991-01-11
IL114174A0 (en)	1995-10-31
ZA903741B (en)	1991-12-24
WO1990014087A1 (en)	1990-11-29
NO914485L (no)	1991-11-15
NO180268B (no)	1996-12-09
ATE150021T1 (de)	1997-03-15
US5338754A (en)	1994-08-16
DE69030134T2 (de)	1997-06-19
RU2029769C1 (ru)	1995-02-27
PL285190A1 (en)	1991-03-25
WO1990014088A1 (en)	1990-11-29
IL114174A (en)	1996-06-18
CZ284342B6 (cs)	1998-10-14
CZ232890A3 (cs)	1998-07-15
NO180268C (no)	1997-03-19
BR1101053A (pt)	2000-03-28
DE69030134D1 (de)	1997-04-17
CN1047291A (zh)	1990-11-28
FI915403A0 (fi)	1991-11-15
US5391742A (en)	1995-02-21
NO914485D0 (no)	1991-11-15
DK0398578T3 (da)	1997-10-13
PH31464A (en)	1998-11-03
CN1032209C (zh)	1996-07-03
KR920004138B1 (ko)	1992-05-25
US5185343A (en)	1993-02-09
JPH0735368B2 (ja)	1995-04-19
SK232890A3 (en)	1998-11-04
PL163580B1 (pl)	1994-04-29
SK279476B6 (sk)	1998-11-04

Legal Events

Date	Code	Title
1997-01-10	FF	Patent granted
1997-02-18	KB	Patent renewed
2000-08-31	KB	Patent renewed
2004-06-20	KB	Patent renewed
2009-07-20	MM9K	Patent not in force due to non-payment of renewal fees

Publication	Publication Date	Title
US5391742A (en)	1995-02-21	Intermediates for 2-piperidino-1-alkanols
US5272160A (en)	1993-12-21	2-piperidino-1-alkanol derivatives as antiischemic agents
CA2016860C (en)	1998-07-28	2-piperidino-1-alkanol derivatives as antiischemic agents
CA2080475C (en)	2001-04-17	Neuroprotective indolone and related derivatives
CA2003422C (en)	1999-12-21	Quinuclidines, their use as medicaments and processes for their preparation
JP5779181B2 (ja)	2015-09-16	（４−フェニル−ピペリジン−１−イル）−［５−（１ｈ−ピラゾール−４−イル）−チオフェン−３−イル］−メタノン化合物及びそれらの使用
EP0441506B1 (en)	1994-07-20	Neuroprotective 3-piperidino-4-hydrosychroman derivatives
NZ284852A (en)	1998-06-26	3-(piperidin-1-yl)-chroman-4,7-diol and 1-(4-hydrophenyl)-2-(piperidin-1-yl) alkanol derivatives; medicaments; used as a neuroprotective agent
US5710168A (en)	1998-01-20	2-piperidino-1-alkanol derivatives as neuroprotective agents
IE921215A1 (en)	1992-10-21	Prodrug esters of phenolic 2-piperidino-1-alkanols
US5527912A (en)	1996-06-18	Intermediates for 2-piperidino-1-alkanol derivatives
NZ241346A (en)	1992-10-28	Phenyl- or thienyl-substituted 8-azabicyclo (3,2,1) octane; use as neuroprotective agents
HK1000468B (en)	1998-03-27	2-piperidino-1-alkanol derivatives as antiischemic agents