AP755A - (1s,2s)-1-(4-Hydroxyphenyl)-2-(4-Hydroxy-4-Phenylpiperidin-1-Y1)-1-Propanol methanesulfonate trihydrate. - Google Patents

(1s,2s)-1-(4-Hydroxyphenyl)-2-(4-Hydroxy-4-Phenylpiperidin-1-Y1)-1-Propanol methanesulfonate trihydrate. Download PDF

Info

Publication number: AP755A
Authority: AP; ARIPO
Prior art keywords: disease; mammal; parkinson; trihydrate; dopamine
Prior art date: 1995-08-11

Application number

APAP/P/1996/000856A

Other languages

English (en)

Other versions

AP9600856A0 (en

Inventor

Marta Maria Andino

Terry Gene Sinay

Eugerne Fred Fiese

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.)

1995-08-11

Filing date

1996-08-08

Publication date

1999-08-02

1996-08-08 Application filed by Pfizer filed Critical Pfizer

1996-10-31 Publication of AP9600856A0 publication Critical patent/AP9600856A0/xx

1999-08-02 Application granted granted Critical

1999-08-02 Publication of AP755A publication Critical patent/AP755A/en

Links

LKGCPYOBWLSCTK-UHFFFAOYSA-N methanesulfonic acid;trihydrate Chemical compound O.O.O.CS(O)(=O)=O LKGCPYOBWLSCTK-UHFFFAOYSA-N 0.000 title claims description 32
BDERNNFJNOPAEC-UHFFFAOYSA-N 1-propanol Substances CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 title claims description 13
238000000034 method Methods 0.000 claims abstract description 19
208000015114 central nervous system disease Diseases 0.000 claims abstract description 10
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 24
239000003814 drug Substances 0.000 claims description 24
208000018737 Parkinson disease Diseases 0.000 claims description 23
241000124008 Mammalia Species 0.000 claims description 22
229940079593 drug Drugs 0.000 claims description 22
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
208000035475 disorder Diseases 0.000 claims description 19
229940044613 1-propanol Drugs 0.000 claims description 12
HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 claims description 12
239000000556 agonist Substances 0.000 claims description 12
229960003638 dopamine Drugs 0.000 claims description 12
201000006474 Brain Ischemia Diseases 0.000 claims description 11
206010008120 Cerebral ischaemia Diseases 0.000 claims description 11
208000030886 Traumatic Brain injury Diseases 0.000 claims description 11
206010008118 cerebral infarction Diseases 0.000 claims description 11
230000009529 traumatic brain injury Effects 0.000 claims description 11
206010065040 AIDS dementia complex Diseases 0.000 claims description 10
208000007848 Alcoholism Diseases 0.000 claims description 10
208000019901 Anxiety disease Diseases 0.000 claims description 10
208000023105 Huntington disease Diseases 0.000 claims description 10
208000013016 Hypoglycemia Diseases 0.000 claims description 10
208000019695 Migraine disease Diseases 0.000 claims description 10
208000002193 Pain Diseases 0.000 claims description 10
208000028017 Psychotic disease Diseases 0.000 claims description 10
208000005392 Spasm Diseases 0.000 claims description 10
208000006011 Stroke Diseases 0.000 claims description 10
208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims description 10
206010046543 Urinary incontinence Diseases 0.000 claims description 10
208000029650 alcohol withdrawal Diseases 0.000 claims description 10
230000036506 anxiety Effects 0.000 claims description 10
230000003412 degenerative effect Effects 0.000 claims description 10
206010013663 drug dependence Diseases 0.000 claims description 10
206010015037 epilepsy Diseases 0.000 claims description 10
230000002218 hypoglycaemic effect Effects 0.000 claims description 10
206010027599 migraine Diseases 0.000 claims description 10
208000011117 substance-related disease Diseases 0.000 claims description 10
208000024827 Alzheimer disease Diseases 0.000 claims description 9
230000002964 excitative effect Effects 0.000 claims description 9
208000024891 symptom Diseases 0.000 claims description 9
238000011282 treatment Methods 0.000 claims description 9
206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 8
208000005314 Multi-Infarct Dementia Diseases 0.000 claims description 6
201000004810 Vascular dementia Diseases 0.000 claims description 6
239000003795 chemical substances by application Substances 0.000 claims description 6
239000003136 dopamine receptor stimulating agent Substances 0.000 claims description 6
210000001103 thalamus Anatomy 0.000 claims description 5
230000003042 antagnostic effect Effects 0.000 claims description 4
229940052760 dopamine agonists Drugs 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
230000002708 enhancing effect Effects 0.000 claims description 4
239000011885 synergistic combination Substances 0.000 claims description 4
210000002071 ventral thalamic nuclei Anatomy 0.000 claims description 4
WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims description 3
WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 claims description 3
239000003112 inhibitor Substances 0.000 claims description 3
229960004502 levodopa Drugs 0.000 claims description 3
229940123685 Monoamine oxidase inhibitor Drugs 0.000 claims description 2
239000000048 adrenergic agonist Substances 0.000 claims description 2
239000000674 adrenergic antagonist Substances 0.000 claims description 2
229940126157 adrenergic receptor agonist Drugs 0.000 claims description 2
230000028436 dopamine uptake Effects 0.000 claims description 2
239000000221 dopamine uptake inhibitor Substances 0.000 claims description 2
229940052764 dopaminergic anti-parkinson drug mao b inhibitors Drugs 0.000 claims description 2
239000002899 monoamine oxidase inhibitor Substances 0.000 claims description 2
239000003402 opiate agonist Substances 0.000 claims description 2
230000013275 serotonin uptake Effects 0.000 claims description 2
102100022738 5-hydroxytryptamine receptor 1A Human genes 0.000 claims 1
101710138638 5-hydroxytryptamine receptor 1A Proteins 0.000 claims 1
239000003543 catechol methyltransferase inhibitor Substances 0.000 claims 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 abstract description 19
150000004684 trihydrates Chemical class 0.000 abstract description 8
QEMSVZNTSXPFJA-HNAYVOBHSA-N 1-[(1s,2s)-1-hydroxy-1-(4-hydroxyphenyl)propan-2-yl]-4-phenylpiperidin-4-ol Chemical compound C1([C@H](O)[C@H](C)N2CCC(O)(CC2)C=2C=CC=CC=2)=CC=C(O)C=C1 QEMSVZNTSXPFJA-HNAYVOBHSA-N 0.000 abstract description 3
239000000047 product Substances 0.000 description 35
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
239000000725 suspension Substances 0.000 description 29
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
239000012458 free base Substances 0.000 description 15
239000000243 solution Substances 0.000 description 14
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 12
239000011521 glass Substances 0.000 description 12
229930195712 glutamate Natural products 0.000 description 11
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
HOKKHZGPKSLGJE-UHFFFAOYSA-N N-methyl-D-aspartic acid Natural products CNC(C(O)=O)CC(O)=O HOKKHZGPKSLGJE-UHFFFAOYSA-N 0.000 description 9
230000000694 effects Effects 0.000 description 9
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
150000001875 compounds Chemical class 0.000 description 8
230000002461 excitatory amino acid Effects 0.000 description 8
239000003257 excitatory amino acid Substances 0.000 description 8
239000001963 growth medium Substances 0.000 description 8
238000007605 air drying Methods 0.000 description 7
239000000203 mixture Substances 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
238000004458 analytical method Methods 0.000 description 6
238000006243 chemical reaction Methods 0.000 description 6
238000010992 reflux Methods 0.000 description 6
238000004809 thin layer chromatography Methods 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
239000005557 antagonist Substances 0.000 description 5
210000004027 cell Anatomy 0.000 description 5
102000005962 receptors Human genes 0.000 description 5
108020003175 receptors Proteins 0.000 description 5
238000001228 spectrum Methods 0.000 description 5
206010012289 Dementia Diseases 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
238000002474 experimental method Methods 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
239000012299 nitrogen atmosphere Substances 0.000 description 4
238000000634 powder X-ray diffraction Methods 0.000 description 4
239000007787 solid Substances 0.000 description 4
UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
108090000862 Ion Channels Proteins 0.000 description 3
102000004310 Ion Channels Human genes 0.000 description 3
102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 3
108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
230000000875 corresponding effect Effects 0.000 description 3
238000001914 filtration Methods 0.000 description 3
230000001057 ionotropic effect Effects 0.000 description 3
239000000463 material Substances 0.000 description 3
230000000324 neuroprotective effect Effects 0.000 description 3
210000002966 serum Anatomy 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
239000000126 substance Substances 0.000 description 3
150000003892 tartrate salts Chemical class 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
230000001988 toxicity Effects 0.000 description 3
231100000419 toxicity Toxicity 0.000 description 3
238000001291 vacuum drying Methods 0.000 description 3
108091003079 Bovine Serum Albumin Proteins 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
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 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
238000005481 NMR spectroscopy Methods 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 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
DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
238000002835 absorbance Methods 0.000 description 2
230000002253 anti-ischaemic effect Effects 0.000 description 2
239000012267 brine Substances 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
230000002860 competitive effect Effects 0.000 description 2
238000005100 correlation spectroscopy Methods 0.000 description 2
239000013078 crystal Substances 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
238000002518 distortionless enhancement with polarization transfer Methods 0.000 description 2
238000001035 drying Methods 0.000 description 2
239000012091 fetal bovine serum Substances 0.000 description 2
238000005187 foaming Methods 0.000 description 2
239000008103 glucose Substances 0.000 description 2
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 2
230000001965 increasing effect Effects 0.000 description 2
239000002674 ointment Substances 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
238000007747 plating Methods 0.000 description 2
-1 polyethylene Polymers 0.000 description 2
230000002441 reversible effect Effects 0.000 description 2
150000003839 salts Chemical class 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
PFNFFQXMRSDOHW-UHFFFAOYSA-N spermine Chemical compound NCCCNCCCCNCCCN PFNFFQXMRSDOHW-UHFFFAOYSA-N 0.000 description 2
229960005322 streptomycin Drugs 0.000 description 2
239000003981 vehicle Substances 0.000 description 2
230000035899 viability Effects 0.000 description 2
230000004580 weight loss Effects 0.000 description 2
MGRVRXRGTBOSHW-UHFFFAOYSA-N (aminomethyl)phosphonic acid Chemical compound NCP(O)(O)=O MGRVRXRGTBOSHW-UHFFFAOYSA-N 0.000 description 1
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
WLVPRARCUSRDNI-UHFFFAOYSA-N 2-hydroxy-1-phenyl-1-propanone Chemical compound CC(O)C(=O)C1=CC=CC=C1 WLVPRARCUSRDNI-UHFFFAOYSA-N 0.000 description 1
238000005084 2D-nuclear magnetic resonance Methods 0.000 description 1
102000015404 Amino Acid Receptors Human genes 0.000 description 1
108010025177 Amino Acid Receptors Proteins 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-LWMBPPNESA-L D-tartrate(2-) Chemical class [O-]C(=O)[C@@H](O)[C@H](O)C([O-])=O FEWJPZIEWOKRBE-LWMBPPNESA-L 0.000 description 1
208000006558 Dental Calculus Diseases 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
108091006027 G proteins Proteins 0.000 description 1
102000030782 GTP binding Human genes 0.000 description 1
108091000058 GTP-Binding Proteins 0.000 description 1
102000018899 Glutamate Receptors Human genes 0.000 description 1
108010027915 Glutamate Receptors Proteins 0.000 description 1
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
206010029350 Neurotoxicity Diseases 0.000 description 1
229930182555 Penicillin Natural products 0.000 description 1
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
239000004698 Polyethylene Substances 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
208000034189 Sclerosis Diseases 0.000 description 1
206010044221 Toxic encephalopathy Diseases 0.000 description 1
102000004357 Transferases Human genes 0.000 description 1
108090000992 Transferases Proteins 0.000 description 1
238000002441 X-ray diffraction Methods 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
235000001014 amino acid Nutrition 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
235000003704 aspartic acid Nutrition 0.000 description 1
238000003556 assay Methods 0.000 description 1
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
210000000481 breast Anatomy 0.000 description 1
238000009395 breeding Methods 0.000 description 1
230000001488 breeding effect Effects 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
239000000872 buffer Substances 0.000 description 1
239000008366 buffered solution Substances 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
238000004113 cell culture Methods 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
230000001054 cortical effect Effects 0.000 description 1
230000001086 cytosolic effect Effects 0.000 description 1
YKGMKSIHIVVYKY-UHFFFAOYSA-N dabrafenib mesylate Chemical compound CS(O)(=O)=O.S1C(C(C)(C)C)=NC(C=2C(=C(NS(=O)(=O)C=3C(=CC=CC=3F)F)C=CC=2)F)=C1C1=CC=NC(N)=N1 YKGMKSIHIVVYKY-UHFFFAOYSA-N 0.000 description 1
230000006378 damage Effects 0.000 description 1
238000007405 data analysis Methods 0.000 description 1
230000007850 degeneration Effects 0.000 description 1
201000010099 disease Diseases 0.000 description 1
239000006274 endogenous ligand Substances 0.000 description 1
238000011067 equilibration Methods 0.000 description 1
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
230000009540 excitatory neurotransmission Effects 0.000 description 1
239000004060 excitotoxin Substances 0.000 description 1
239000000284 extract Substances 0.000 description 1
230000001605 fetal effect Effects 0.000 description 1
ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000013922 glutamic acid Nutrition 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
239000008187 granular material Substances 0.000 description 1
230000000971 hippocampal effect Effects 0.000 description 1
239000012456 homogeneous solution Substances 0.000 description 1
230000036571 hydration Effects 0.000 description 1
238000006703 hydration reaction Methods 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
AUONNNVJUCSETH-UHFFFAOYSA-N icosanoyl icosanoate Chemical compound CCCCCCCCCCCCCCCCCCCC(=O)OC(=O)CCCCCCCCCCCCCCCCCCC AUONNNVJUCSETH-UHFFFAOYSA-N 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
238000011534 incubation Methods 0.000 description 1
208000014674 injury Diseases 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
239000007788 liquid Substances 0.000 description 1
239000006210 lotion Substances 0.000 description 1
239000012528 membrane Substances 0.000 description 1
102000006239 metabotropic receptors Human genes 0.000 description 1
108020004083 metabotropic receptors Proteins 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
238000000386 microscopy Methods 0.000 description 1
239000007758 minimum essential medium Substances 0.000 description 1
230000000877 morphologic effect Effects 0.000 description 1
210000000653 nervous system Anatomy 0.000 description 1
101150006061 neur gene Proteins 0.000 description 1
230000001537 neural effect Effects 0.000 description 1
210000002569 neuron Anatomy 0.000 description 1
230000007135 neurotoxicity Effects 0.000 description 1
231100000228 neurotoxicity Toxicity 0.000 description 1
239000002858 neurotransmitter agent Substances 0.000 description 1
229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
229940049954 penicillin Drugs 0.000 description 1
150000003906 phosphoinositides Chemical class 0.000 description 1
229920000768 polyamine Polymers 0.000 description 1
229920000573 polyethylene Polymers 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
230000035755 proliferation Effects 0.000 description 1
238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
238000003653 radioligand binding assay Methods 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
239000002464 receptor antagonist Substances 0.000 description 1
229940044551 receptor antagonist Drugs 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000010850 salt effect Methods 0.000 description 1
239000004017 serum-free culture medium Substances 0.000 description 1
230000019491 signal transduction Effects 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
239000012064 sodium phosphate buffer Substances 0.000 description 1
229940054269 sodium pyruvate Drugs 0.000 description 1
229940063675 spermine Drugs 0.000 description 1
210000000278 spinal cord Anatomy 0.000 description 1
239000007858 starting material Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
238000004448 titration Methods 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
230000008733 trauma Effects 0.000 description 1
NRTLTGGGUQIRRT-UHFFFAOYSA-N triethylazanium;bromide Chemical compound [Br-].CC[NH+](CC)CC NRTLTGGGUQIRRT-UHFFFAOYSA-N 0.000 description 1
DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
229940045145 uridine Drugs 0.000 description 1
238000010792 warming Methods 0.000 description 1
239000003643 water by type Substances 0.000 description 1
238000005303 weighing Methods 0.000 description 1
230000004584 weight gain Effects 0.000 description 1
235000019786 weight gain Nutrition 0.000 description 1

Classifications

- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary 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
- 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
- A61P25/06—Antimigraine agents
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Diabetes (AREA)
Psychology (AREA)
Virology (AREA)
Pain & Pain Management (AREA)
Psychiatry (AREA)
Oncology (AREA)
Endocrinology (AREA)
Tropical Medicine & Parasitology (AREA)
AIDS & HIV (AREA)
Molecular Biology (AREA)
Communicable Diseases (AREA)
Hospice & Palliative Care (AREA)
Urology & Nephrology (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Hydrogenated Pyridines (AREA)

APAP/P/1996/000856A 1995-08-11 1996-08-08 (1s,2s)-1-(4-Hydroxyphenyl)-2-(4-Hydroxy-4-Phenylpiperidin-1-Y1)-1-Propanol methanesulfonate trihydrate. AP755A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US223895P	1995-08-11	1995-08-11

Publications (2)

Publication Number	Publication Date
AP9600856A0 AP9600856A0 (en)	1996-10-31
AP755A true AP755A (en)	1999-08-02

Family

ID=21699847

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
APAP/P/1996/000856A AP755A (en)	1995-08-11	1996-08-08	(1s,2s)-1-(4-Hydroxyphenyl)-2-(4-Hydroxy-4-Phenylpiperidin-1-Y1)-1-Propanol methanesulfonate trihydrate.

Country Status (41)

Country	Link
US (1)	US6008233A (de)
EP (1)	EP0843661B1 (de)
JP (1)	JP3099072B2 (de)
KR (1)	KR100291882B1 (de)
CN (2)	CN1198739A (de)
AP (1)	AP755A (de)
AR (1)	AR004676A1 (de)
AT (1)	ATE215072T1 (de)
AU (1)	AU710984B2 (de)
BG (1)	BG63678B1 (de)
BR (1)	BR9610766A (de)
CA (1)	CA2228752C (de)
CO (1)	CO4750830A1 (de)
CZ (1)	CZ296236B6 (de)
DE (1)	DE69620191T2 (de)
DK (1)	DK0843661T3 (de)
DZ (1)	DZ2083A1 (de)
ES (1)	ES2170857T3 (de)
GT (1)	GT199600051A (de)
HR (1)	HRP960372B1 (de)
HU (1)	HUP9802862A3 (de)
IL (1)	IL122649A (de)
IS (1)	IS1945B (de)
MA (1)	MA23957A1 (de)
NO (1)	NO310458B1 (de)
NZ (1)	NZ309134A (de)
OA (1)	OA10664A (de)
PE (1)	PE4898A1 (de)
PL (1)	PL185603B1 (de)
PT (1)	PT843661E (de)
RO (1)	RO120134B1 (de)
RS (1)	RS49521B (de)
RU (1)	RU2140910C1 (de)
SA (1)	SA96170171B1 (de)
SK (1)	SK284209B6 (de)
TN (1)	TNSN96104A1 (de)
TR (1)	TR199800208T1 (de)
TW (1)	TW495502B (de)
UA (1)	UA59341C2 (de)
WO (1)	WO1997007098A1 (de)
ZA (1)	ZA966760B (de)

Families Citing this family (31)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
MX9701282A (es) *	1994-08-18	1997-05-31	Pfizer	Fenoles neuroprotectores.
DK0843661T3 (da) *	1995-08-11	2002-07-22	Pfizer	(1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidin-1-yl)-1-propanolmethansulfonat-trihydrat
GB9820405D0 (en) *	1998-09-18	1998-11-11	Smithkline Beecham Plc	Process
AU3676100A (en) *	1999-04-09	2000-11-14	Mochida Pharmaceutical Co., Ltd.	Remedies for neuropathic pain
GB9920919D0 (en)	1999-09-03	1999-11-10	Sb Pharmco Inc	Novel compound
GB9920917D0 (en)	1999-09-03	1999-11-10	Sb Pharmco Inc	Novel process
US6620830B2 (en) *	2000-04-21	2003-09-16	Pfizer, Inc.	Thyroid receptor ligands
YU27701A (sh) *	2000-04-28	2003-04-30	Pfizer Products Inc.	Postupak za dobijanje trihidrata mezilatne soli 1-(4- hidroksifenil)-2-(4-hidroksi-4-fenilpiperidin-1-il)1-propanola
YU27801A (sh) *	2000-04-28	2003-04-30	Pfizer Products Inc.	Postupak za dobijanje trihidrata mezilatne soli 1-(4- hidroksifenil)-2-(4-hidroksi-4-fenilpiperidin-1-il)-1-propanola i korisnih intermedijera
MXPA03001472A (es) *	2000-08-16	2003-06-06	Upjohn Co	Compuestos para el tratamiento de trastornos adictivos.
EP1186303A3 (de) *	2000-09-06	2003-12-10	Pfizer Products Inc.	Ein Neutrophilhemmender Faktor und ein selektive NMDA-NR2B Rezeptor Antagonisten enthaltende Kombinationspräparate zur Behandlung von Schlaganfällen und traumatischen Gehirnschäden
EP1674087A1 (de)	2000-10-02	2006-06-28	Pfizer Products Inc.	Prophylaktische Verwendung von N-Methyl-D-Aspartat Rezeptor (NMDA) Antagonisten
IL145584A0 (en)	2000-10-02	2002-06-30	Pfizer Prod Inc	Nmda nr2b antagonists for treatment
UA73619C2 (en) *	2000-12-13	2005-08-15	Pfizer Prod Inc	Stable pharmaceutical compositions of nmda receptor agonist (variants) and method of treatment
BRPI0213393B8 (pt)	2001-10-19	2021-05-25	Fujifilm Toyama Chemical Co Ltd	derivados de éter alquílico, ou um de seus sais, processo para produzir um derivado de éter alquílico, derivado de alquil-amida, ou um de seus sais, e, composição farmacêutica
KR100517638B1 (ko)	2002-04-08	2005-09-28	주식회사 엘지생명과학	게미플록사신 산염의 새로운 제조방법
CA2628074C (en)	2005-10-25	2014-01-14	Shionogi & Co., Ltd.	Aminodihydrothiazine derivative
JP5383484B2 (ja)	2007-04-24	2014-01-08	塩野義製薬株式会社	環式基で置換されたアミノジヒドロチアジン誘導体
US8653067B2 (en)	2007-04-24	2014-02-18	Shionogi & Co., Ltd.	Pharmaceutical composition for treating Alzheimer's disease
KR101324426B1 (ko)	2008-06-13	2013-10-31	시오노기세야쿠 가부시키가이샤	β 세크레타제 저해 작용을 갖는 황 함유 복소환 유도체
CN102186841A (zh)	2008-10-22	2011-09-14	盐野义制药株式会社	具有bace1抑制活性的2-氨基嘧啶-4-酮及2-氨基吡啶衍生物
MX2012006491A (es)	2009-12-11	2012-07-03	Shionogi & Co	Derivados de oxazina.
EP2634188A4 (de)	2010-10-29	2014-05-07	Shionogi & Co	Kondensiertes aminodihydropyrimidinderivat
JP5816630B2 (ja)	2010-10-29	2015-11-18	塩野義製薬株式会社	ナフチリジン誘導体
US8883779B2 (en)	2011-04-26	2014-11-11	Shinogi & Co., Ltd.	Oxazine derivatives and a pharmaceutical composition for inhibiting BACE1 containing them
EP2912035A4 (de)	2012-10-24	2016-06-15	Shionogi & Co	Dihydrooxazin- oder oxazepinderivate mit bace1-hemmender wirkung
RU2017107558A (ru)	2014-09-15	2018-10-18	Руджен Холдингс (Кайман) Лимитед	Производные пирролопиримидина в качестве антагонистов nmda-рецептора nr2b
WO2016049048A1 (en) *	2014-09-22	2016-03-31	Rugen Holdings (Cayman) Limited	Treatment of anxiety disorders and autism spectrum disorders
US10221182B2 (en)	2015-02-04	2019-03-05	Rugen Holdings (Cayman) Limited	3,3-difluoro-piperidine derivatives as NR2B NMDA receptor antagonists
KR102613179B1 (ko)	2015-06-01	2023-12-14	뤼겐 홀딩스 (케이맨) 리미티드	Nr2b nmda 수용체 길항제로서의 3,3-디플루오로피페리딘 카바메이트 헤테로사이클릭 화합물
US11000526B2 (en)	2016-11-22	2021-05-11	Rugen Holdings (Cayman) Limited	Treatment of autism spectrum disorders, obsessive-compulsive disorder and anxiety disorders

Citations (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5185343A (en) *	1989-05-17	1993-02-09	Pfizer Inc.	Nortropyl-1-alkanol derivatives as antiischemic agents
US5272160A (en) *	1989-05-17	1993-12-21	Pfizer Inc	2-piperidino-1-alkanol derivatives as antiischemic agents

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
MX9701282A (es) *	1994-08-18	1997-05-31	Pfizer	Fenoles neuroprotectores.
DK0843661T3 (da) *	1995-08-11	2002-07-22	Pfizer	(1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidin-1-yl)-1-propanolmethansulfonat-trihydrat

1996
- 1996-06-20 DK DK96916266T patent/DK0843661T3/da active
- 1996-06-20 RU RU98102116A patent/RU2140910C1/ru not_active IP Right Cessation
- 1996-06-20 PT PT96916266T patent/PT843661E/pt unknown
- 1996-06-20 CN CN96195649A patent/CN1198739A/zh active Pending
- 1996-06-20 PL PL96325050A patent/PL185603B1/pl not_active IP Right Cessation
- 1996-06-20 US US09/011,426 patent/US6008233A/en not_active Expired - Fee Related
- 1996-06-20 CN CNA031584969A patent/CN1615861A/zh active Pending
- 1996-06-20 CA CA002228752A patent/CA2228752C/en not_active Expired - Fee Related
- 1996-06-20 IL IL12264996A patent/IL122649A/xx not_active IP Right Cessation
- 1996-06-20 RO RO98-00231A patent/RO120134B1/ro unknown
- 1996-06-20 KR KR1019980700989A patent/KR100291882B1/ko not_active Expired - Fee Related
- 1996-06-20 TR TR1998/00208T patent/TR199800208T1/xx unknown
- 1996-06-20 AU AU59084/96A patent/AU710984B2/en not_active Ceased
- 1996-06-20 EP EP96916266A patent/EP0843661B1/de not_active Expired - Lifetime
- 1996-06-20 WO PCT/IB1996/000592 patent/WO1997007098A1/en not_active Ceased
- 1996-06-20 SK SK166-98A patent/SK284209B6/sk unknown
- 1996-06-20 BR BR9610766A patent/BR9610766A/pt not_active Application Discontinuation
- 1996-06-20 DE DE69620191T patent/DE69620191T2/de not_active Expired - Fee Related
- 1996-06-20 HU HU9802862A patent/HUP9802862A3/hu unknown
- 1996-06-20 CZ CZ0039098A patent/CZ296236B6/cs not_active IP Right Cessation
- 1996-06-20 JP JP09509083A patent/JP3099072B2/ja not_active Expired - Fee Related
- 1996-06-20 UA UA98020673A patent/UA59341C2/uk unknown
- 1996-06-20 NZ NZ309134A patent/NZ309134A/en unknown
- 1996-06-20 ES ES96916266T patent/ES2170857T3/es not_active Expired - Lifetime
- 1996-06-20 AT AT96916266T patent/ATE215072T1/de not_active IP Right Cessation
- 1996-06-24 TW TW085107571A patent/TW495502B/zh not_active IP Right Cessation
- 1996-07-04 GT GT199600051A patent/GT199600051A/es unknown
- 1996-07-23 SA SA96170171A patent/SA96170171B1/ar unknown
- 1996-08-06 PE PE1996000587A patent/PE4898A1/es not_active Application Discontinuation
- 1996-08-07 MA MA24335A patent/MA23957A1/fr unknown
- 1996-08-07 DZ DZ960127A patent/DZ2083A1/fr active
- 1996-08-07 TN TNTNSN96104A patent/TNSN96104A1/fr unknown
- 1996-08-07 AR ARP960103904A patent/AR004676A1/es unknown
- 1996-08-08 AP APAP/P/1996/000856A patent/AP755A/en active
- 1996-08-08 ZA ZA9606760A patent/ZA966760B/xx unknown
- 1996-08-09 HR HR960372A patent/HRP960372B1/xx not_active IP Right Cessation
- 1996-08-09 RS YU46196A patent/RS49521B/sr unknown
- 1996-08-09 CO CO96042164A patent/CO4750830A1/es unknown
1997
- 1997-12-30 IS IS4643A patent/IS1945B/is unknown
1998
- 1998-02-10 OA OA9800021A patent/OA10664A/en unknown
- 1998-02-10 NO NO19980574A patent/NO310458B1/no unknown
- 1998-02-27 BG BG102289A patent/BG63678B1/bg unknown

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5185343A (en) *	1989-05-17	1993-02-09	Pfizer Inc.	Nortropyl-1-alkanol derivatives as antiischemic agents
US5272160A (en) *	1989-05-17	1993-12-21	Pfizer Inc	2-piperidino-1-alkanol derivatives as antiischemic agents

Also Published As

Publication number	Publication date
AU5908496A (en)	1997-03-12
NO310458B1 (no)	2001-07-09
DK0843661T3 (da)	2002-07-22
JP3099072B2 (ja)	2000-10-16
EP0843661B1 (de)	2002-03-27
IL122649A0 (en)	1998-08-16
TNSN96104A1 (fr)	2005-03-15
IS4643A (is)	1997-12-30
CO4750830A1 (es)	1999-03-31
WO1997007098A1 (en)	1997-02-27
ATE215072T1 (de)	2002-04-15
HRP960372B1 (en)	2003-04-30
RS49521B (sr)	2006-10-27
KR100291882B1 (ko)	2001-10-26
CN1615861A (zh)	2005-05-18
CA2228752A1 (en)	1997-02-27
IL122649A (en)	2001-08-26
CN1198739A (zh)	1998-11-11
HRP960372A2 (en)	1998-04-30
IS1945B (is)	2004-08-13
ES2170857T3 (es)	2002-08-16
EP0843661A1 (de)	1998-05-27
DE69620191D1 (de)	2002-05-02
AU710984B2 (en)	1999-10-07
HUP9802862A2 (hu)	1999-04-28
RO120134B1 (ro)	2005-09-30
PL325050A1 (en)	1998-07-06
JPH10510552A (ja)	1998-10-13
BR9610766A (pt)	1999-07-13
AP9600856A0 (en)	1996-10-31
DZ2083A1 (fr)	2002-10-23
PL185603B1 (pl)	2003-06-30
ZA966760B (en)	1998-02-09
BG63678B1 (bg)	2002-09-30
MA23957A1 (fr)	1997-04-01
GT199600051A (es)	1997-12-26
DE69620191T2 (de)	2002-07-18
PT843661E (pt)	2002-07-31
SK16698A3 (en)	1999-06-11
HUP9802862A3 (en)	1999-05-28
RU2140910C1 (ru)	1999-11-10
PE4898A1 (es)	1998-03-16
MX9801149A (es)	1998-05-31
TW495502B (en)	2002-07-21
US6008233A (en)	1999-12-28
KR19990036321A (ko)	1999-05-25
NO980574D0 (no)	1998-02-10
TR199800208T1 (de)	1998-05-21
YU46196A (sh)	1999-07-28
CZ296236B6 (cs)	2006-02-15
NZ309134A (en)	1999-09-29
SA96170171B1 (ar)	2006-05-20
NO980574L (no)	1998-02-10
UA59341C2 (uk)	2003-09-15
CA2228752C (en)	2002-12-10
AR004676A1 (es)	1999-03-10
OA10664A (en)	2000-11-06
SK284209B6 (en)	2004-11-03
BG102289A (en)	1998-09-30
CZ39098A3 (cs)	1999-02-17

Publication	Publication Date	Title
AP755A (en)	1999-08-02	(1s,2s)-1-(4-Hydroxyphenyl)-2-(4-Hydroxy-4-Phenylpiperidin-1-Y1)-1-Propanol methanesulfonate trihydrate.
US5716961A (en)	1998-02-10	Treatment of tinnitus using neuroprotective agents
EP0741724B1 (de)	1999-08-11	Neuroprotektive chroman verbindungen
RU2203888C2 (ru)	2003-05-10	Способы получения метансульфонат тригидрата и d-(-)-тартратной соли (1s,2s)-1-(4-гидроксифенил)-2-(4-гидрокси-4-фенилпиперидин-1-ил)-1- пропанола
HK1073790A (en)	2005-10-21	(1s, 2s) -1- (4-hydroxyphenyl) -2- (4-hydroxy -4- phenylpiperidin-1-yl)-1-propanolmethanesulfonate trihydrate
MXPA98001149A (en)	1998-10-23	Metansulfonate of (1s, 2s) -1- (4-hydroxypenyl) -2- (4-hydroxy-4-phenylpiperidin-1-il) -1-propanoltrihydrate and use of mi
AU2009310927A1 (en)	2010-05-06	Piperidine derivative, piperazine derivative and agent for treatment of disease involving central nervous system disorders
EP1785415A1 (de)	2007-05-16	Piperidinderivat oder pharmazeutisch unbedenkliches salz davon