SK146398A3 - Use of phosphonic acid esters for the treatment of functional disorders of the brain and depression - Google Patents

Use of phosphonic acid esters for the treatment of functional disorders of the brain and depression Download PDF

Info

Publication number: SK146398A3
Authority: SK; Slovakia
Prior art keywords: dimethyl ester; trichloroethane; phosphonic acid; acid dimethyl; trifluoroethane
Prior art date: 1996-04-25

Application number

SK1463-98A

Other languages

English (en)

Slovak (sk)

Inventor

Fritz Maurer

Bernard Schmidt

Stephan Lensky

Der Staay Franz-Josef Van

Richard J Fanelli

David R Britelli

Original Assignee

Troponwerke Gmbh & Co Kg

Bayer Ag

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.)

1996-04-25

Filing date

1997-04-17

Publication date

1999-06-11

1997-04-17 Application filed by Troponwerke Gmbh & Co Kg, Bayer Ag filed Critical Troponwerke Gmbh & Co Kg

1999-06-11 Publication of SK146398A3 publication Critical patent/SK146398A3/sk

Links

150000003008 phosphonic acid esters Chemical class 0.000 title claims abstract description 15
210000004556 brain Anatomy 0.000 title abstract description 4
230000002265 prevention Effects 0.000 claims abstract description 10
-1 1,1-dichloroethyl Chemical group 0.000 claims description 48
150000001875 compounds Chemical class 0.000 claims description 45
OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 claims description 36
125000000217 alkyl group Chemical group 0.000 claims description 29
238000000034 method Methods 0.000 claims description 24
125000004432 carbon atom Chemical group C* 0.000 claims description 23
239000002253 acid Substances 0.000 claims description 21
229910052739 hydrogen Inorganic materials 0.000 claims description 16
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
230000008569 process Effects 0.000 claims description 16
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
239000001257 hydrogen Substances 0.000 claims description 14
239000002904 solvent Substances 0.000 claims description 13
ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 11
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 claims description 10
239000000203 mixture Substances 0.000 claims description 9
238000002360 preparation method Methods 0.000 claims description 9
238000006243 chemical reaction Methods 0.000 claims description 8
125000004673 propylcarbonyl group Chemical group 0.000 claims description 8
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 7
229910052760 oxygen Inorganic materials 0.000 claims description 7
150000003839 salts Chemical class 0.000 claims description 7
229910052717 sulfur Inorganic materials 0.000 claims description 7
208000014644 Brain disease Diseases 0.000 claims description 6
125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 claims description 6
239000003814 drug Substances 0.000 claims description 6
230000001225 therapeutic effect Effects 0.000 claims description 6
229910052783 alkali metal Inorganic materials 0.000 claims description 5
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 5
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
239000011230 binding agent Substances 0.000 claims description 5
239000013256 coordination polymer Substances 0.000 claims description 5
125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 5
150000002148 esters Chemical class 0.000 claims description 5
238000009472 formulation Methods 0.000 claims description 5
125000004430 oxygen atom Chemical group O* 0.000 claims description 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 claims description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
229910052784 alkaline earth metal Inorganic materials 0.000 claims description 4
125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims description 4
125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 4
BHVWDFJQEHZKIY-UHFFFAOYSA-N dimethoxy(sulfanylidene)-lambda5-phosphane Chemical compound COP(=S)OC BHVWDFJQEHZKIY-UHFFFAOYSA-N 0.000 claims description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
ZTBNJVXGHSZBOZ-UHFFFAOYSA-N COP(OC)=O.C(C)(C)(C)C(=O)OCC(Cl)(Cl)Cl Chemical compound COP(OC)=O.C(C)(C)(C)C(=O)OCC(Cl)(Cl)Cl ZTBNJVXGHSZBOZ-UHFFFAOYSA-N 0.000 claims description 3
150000001342 alkaline earth metals Chemical class 0.000 claims description 3
150000001244 carboxylic acid anhydrides Chemical class 0.000 claims description 3
150000002366 halogen compounds Chemical class 0.000 claims description 3
229910052500 inorganic mineral Inorganic materials 0.000 claims description 3
239000011707 mineral Substances 0.000 claims description 3
239000001301 oxygen Substances 0.000 claims description 3
UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 claims description 3
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
KZHGNHTVCUWRKR-UHFFFAOYSA-N 1-dimethoxyphosphorylethanol Chemical compound COP(=O)(OC)C(C)O KZHGNHTVCUWRKR-UHFFFAOYSA-N 0.000 claims description 2
SBFCYAXKHUAJBN-UHFFFAOYSA-N COP(OC)=O.COC(=O)OCC(Cl)(Cl)Cl Chemical compound COP(OC)=O.COC(=O)OCC(Cl)(Cl)Cl SBFCYAXKHUAJBN-UHFFFAOYSA-N 0.000 claims description 2
WVZBXRLTJHYOAI-UHFFFAOYSA-N COP(OC)=O.OC(C)C Chemical compound COP(OC)=O.OC(C)C WVZBXRLTJHYOAI-UHFFFAOYSA-N 0.000 claims description 2
GTUUDCLYHLVFON-UHFFFAOYSA-N COP(OC)=O.OCC(F)(F)F Chemical compound COP(OC)=O.OCC(F)(F)F GTUUDCLYHLVFON-UHFFFAOYSA-N 0.000 claims description 2
150000003863 ammonium salts Chemical class 0.000 claims description 2
230000003197 catalytic effect Effects 0.000 claims description 2
125000004774 dichlorofluoromethyl group Chemical group FC(Cl)(Cl)* 0.000 claims description 2
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 2
125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 claims description 2
125000006125 ethylsulfonyl group Chemical group 0.000 claims description 2
125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 2
125000005843 halogen group Chemical group 0.000 claims description 2
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 2
125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 claims description 2
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 2
229910017464 nitrogen compound Inorganic materials 0.000 claims description 2
150000002830 nitrogen compounds Chemical class 0.000 claims description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
125000004742 propyloxycarbonyl group Chemical group 0.000 claims description 2
125000004434 sulfur atom Chemical group 0.000 claims description 2
125000006253 t-butylcarbonyl group Chemical group [H]C([H])([H])C(C(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
UPQQXPKAYZYUKO-UHFFFAOYSA-N 2,2,2-trichloroacetamide Chemical compound OC(=N)C(Cl)(Cl)Cl UPQQXPKAYZYUKO-UHFFFAOYSA-N 0.000 claims 1
KPWDGTGXUYRARH-UHFFFAOYSA-N 2,2,2-trichloroethanol Chemical compound OCC(Cl)(Cl)Cl KPWDGTGXUYRARH-UHFFFAOYSA-N 0.000 claims 1
WSOBLQNNNMEZAF-UHFFFAOYSA-N 2,2,2-trichloroethyl methanesulfonate Chemical compound CS(=O)(=O)OCC(Cl)(Cl)Cl WSOBLQNNNMEZAF-UHFFFAOYSA-N 0.000 claims 1
KIZYLMJGNACPOQ-UHFFFAOYSA-N P(OC)(OC)=O.OCC(C)(C)C Chemical compound P(OC)(OC)=O.OCC(C)(C)C KIZYLMJGNACPOQ-UHFFFAOYSA-N 0.000 claims 1
HKHYOUJDRIQXTK-UHFFFAOYSA-N P(OC)(OC)=O.OCC(CCl)(Cl)Cl Chemical compound P(OC)(OC)=O.OCC(CCl)(Cl)Cl HKHYOUJDRIQXTK-UHFFFAOYSA-N 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
238000012360 testing method Methods 0.000 description 36
241001465754 Metazoa Species 0.000 description 15
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
241000700159 Rattus Species 0.000 description 10
238000012549 training Methods 0.000 description 10
230000000694 effects Effects 0.000 description 8
241000699670 Mus sp. Species 0.000 description 7
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
239000000126 substance Substances 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
208000024827 Alzheimer disease Diseases 0.000 description 5
206010012289 Dementia Diseases 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
230000037396 body weight Effects 0.000 description 5
230000001149 cognitive effect Effects 0.000 description 5
208000035475 disorder Diseases 0.000 description 5
229960001952 metrifonate Drugs 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
NFACJZMKEDPNKN-UHFFFAOYSA-N trichlorfon Chemical compound COP(=O)(OC)C(O)C(Cl)(Cl)Cl NFACJZMKEDPNKN-UHFFFAOYSA-N 0.000 description 5
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
ITQTTZVARXURQS-UHFFFAOYSA-N 3-methylpyridine Chemical compound CC1=CC=CN=C1 ITQTTZVARXURQS-UHFFFAOYSA-N 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
239000000935 antidepressant agent Substances 0.000 description 4
229940005513 antidepressants Drugs 0.000 description 4
125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
230000002996 emotional effect Effects 0.000 description 4
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 3
102000003914 Cholinesterases Human genes 0.000 description 3
108090000322 Cholinesterases Proteins 0.000 description 3
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
230000006399 behavior Effects 0.000 description 3
229940048961 cholinesterase Drugs 0.000 description 3
208000010877 cognitive disease Diseases 0.000 description 3
238000001816 cooling Methods 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
238000002844 melting Methods 0.000 description 3
230000008018 melting Effects 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
239000008194 pharmaceutical composition Substances 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 3
239000013558 reference substance Substances 0.000 description 3
229910052938 sodium sulfate Inorganic materials 0.000 description 3
235000011152 sodium sulphate Nutrition 0.000 description 3
230000009182 swimming Effects 0.000 description 3
RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 2
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VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
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OEBRKCOSUFCWJD-UHFFFAOYSA-N dichlorvos Chemical compound COP(=O)(OC)OC=C(Cl)Cl OEBRKCOSUFCWJD-UHFFFAOYSA-N 0.000 description 2
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CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 description 1
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HCMLWTSVGXPTMD-UHFFFAOYSA-N COP(OC)=S.C(C)(C)(C)C(=O)OCC(Cl)(Cl)Cl Chemical compound COP(OC)=S.C(C)(C)(C)C(=O)OCC(Cl)(Cl)Cl HCMLWTSVGXPTMD-UHFFFAOYSA-N 0.000 description 1
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 1
229910001335 Galvanized steel Inorganic materials 0.000 description 1
208000023105 Huntington disease Diseases 0.000 description 1
229940124913 IPOL Drugs 0.000 description 1
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 1
206010061216 Infarction Diseases 0.000 description 1
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
208000019022 Mood disease Diseases 0.000 description 1
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
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NVCISMLILWNMIY-UHFFFAOYSA-N P(O)(O)=O.CC(C(CCl)(Cl)Cl)(O)C Chemical compound P(O)(O)=O.CC(C(CCl)(Cl)Cl)(O)C NVCISMLILWNMIY-UHFFFAOYSA-N 0.000 description 1
SBZVGXCNSUNLTI-UHFFFAOYSA-N P(O)(O)=O.OCC(Cl)(Cl)Cl Chemical compound P(O)(O)=O.OCC(Cl)(Cl)Cl SBZVGXCNSUNLTI-UHFFFAOYSA-N 0.000 description 1
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KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
229910000831 Steel Inorganic materials 0.000 description 1
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239000004480 active ingredient Substances 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
229910000102 alkali metal hydride Inorganic materials 0.000 description 1
150000008046 alkali metal hydrides Chemical class 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
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239000000921 anthelmintic agent Substances 0.000 description 1
150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
235000013405 beer Nutrition 0.000 description 1
238000009227 behaviour therapy Methods 0.000 description 1
230000003542 behavioural effect Effects 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
238000004166 bioassay Methods 0.000 description 1
230000008033 biological extinction Effects 0.000 description 1
229910000019 calcium carbonate Inorganic materials 0.000 description 1
AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical class [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
235000011116 calcium hydroxide Nutrition 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
229910002092 carbon dioxide Inorganic materials 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
230000001713 cholinergic effect Effects 0.000 description 1
239000000544 cholinesterase inhibitor Substances 0.000 description 1
230000007278 cognition impairment Effects 0.000 description 1
230000003930 cognitive ability Effects 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
239000000470 constituent Substances 0.000 description 1
239000002178 crystalline material Substances 0.000 description 1
230000002354 daily effect Effects 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
230000003412 degenerative effect Effects 0.000 description 1
MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 1
CZHYKKAKFWLGJO-UHFFFAOYSA-N dimethyl phosphite Chemical compound COP([O-])OC CZHYKKAKFWLGJO-UHFFFAOYSA-N 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
230000003203 everyday effect Effects 0.000 description 1
235000013305 food Nutrition 0.000 description 1
239000008397 galvanized steel Substances 0.000 description 1
238000004817 gas chromatography Methods 0.000 description 1
239000011521 glass Substances 0.000 description 1
239000008187 granular material Substances 0.000 description 1
150000008282 halocarbons Chemical class 0.000 description 1
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
230000006872 improvement Effects 0.000 description 1
230000007574 infarction Effects 0.000 description 1
239000002917 insecticide Substances 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
239000007788 liquid Substances 0.000 description 1
SIAPCJWMELPYOE-UHFFFAOYSA-N lithium hydride Chemical compound [LiH] SIAPCJWMELPYOE-UHFFFAOYSA-N 0.000 description 1
229910000103 lithium hydride Inorganic materials 0.000 description 1
230000004807 localization Effects 0.000 description 1
230000007774 longterm Effects 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
230000010534 mechanism of action Effects 0.000 description 1
230000015654 memory Effects 0.000 description 1
206010027175 memory impairment Diseases 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
XRKQMIFKHDXFNQ-UHFFFAOYSA-N n-cyclohexyl-n-ethylcyclohexanamine Chemical compound C1CCCCC1N(CC)C1CCCCC1 XRKQMIFKHDXFNQ-UHFFFAOYSA-N 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000012071 phase Substances 0.000 description 1
239000006187 pill Substances 0.000 description 1
239000004033 plastic Substances 0.000 description 1
230000009714 positive regulation of behavior Effects 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 1
239000011736 potassium bicarbonate Substances 0.000 description 1
235000015497 potassium bicarbonate Nutrition 0.000 description 1
229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
235000011181 potassium carbonates Nutrition 0.000 description 1
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
235000011118 potassium hydroxide Nutrition 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
239000000843 powder Substances 0.000 description 1
235000008476 powdered milk Nutrition 0.000 description 1
239000002243 precursor Substances 0.000 description 1
230000003449 preventive effect Effects 0.000 description 1
FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
238000000746 purification Methods 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
238000012216 screening Methods 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
235000017550 sodium carbonate Nutrition 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
235000011121 sodium hydroxide Nutrition 0.000 description 1
MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
239000000243 solution Substances 0.000 description 1
230000006886 spatial memory Effects 0.000 description 1
238000012453 sprague-dawley rat model Methods 0.000 description 1
239000010959 steel Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
239000011593 sulfur Chemical group 0.000 description 1
239000000725 suspension Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 1
229960001685 tacrine Drugs 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
238000005303 weighing Methods 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Classifications

- 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
- A61K31/66—Phosphorus compounds
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4006—Esters of acyclic acids which can have further substituents on alkyl
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Landscapes

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

SK1463-98A 1996-04-25 1997-04-17 Use of phosphonic acid esters for the treatment of functional disorders of the brain and depression SK146398A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE19616471A DE19616471A1 (de)	1996-04-25	1996-04-25	Phosponsäureester zur Behandlung von Hirnleistungsstörungen und Depressionen
PCT/US1997/006469 WO1997039756A1 (en)	1996-04-25	1997-04-17	Use of phosphonic acid esters for the treatment of functional disorders of the brain and depression

Publications (1)

Publication Number	Publication Date
SK146398A3 true SK146398A3 (en)	1999-06-11

Family

ID=7792381

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1463-98A SK146398A3 (en)	1996-04-25	1997-04-17	Use of phosphonic acid esters for the treatment of functional disorders of the brain and depression

Country Status (19)

Country	Link
EP (1)	EP0896540A1 (cs)
JP (1)	JP2000510455A (cs)
KR (1)	KR20000010611A (cs)
AR (1)	AR006870A1 (cs)
AU (1)	AU2462397A (cs)
BG (1)	BG102864A (cs)
BR (1)	BR9709300A (cs)
CA (1)	CA2252567A1 (cs)
CZ (1)	CZ343498A3 (cs)
DE (1)	DE19616471A1 (cs)
HU (1)	HUP9903366A3 (cs)
ID (1)	ID16678A (cs)
IL (1)	IL126698A0 (cs)
NO (1)	NO984964L (cs)
PL (1)	PL333464A1 (cs)
SK (1)	SK146398A3 (cs)
TR (1)	TR199802137T2 (cs)
WO (1)	WO1997039756A1 (cs)
ZA (1)	ZA973538B (cs)

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE1078370B (de) *	1958-09-16	1960-03-24	Norddeutsche Affinerie	Schaedlingsbekaempfungsmittel
US3069312A (en) *	1960-09-28	1962-12-18	California Research Corp	N-substituted dimethyl 1-carbamoyloxy-2, 2, 2-trichloroethyl phosphonates as insecticidal compositions
NL292791A (cs) *	1962-05-16	1900-01-01
DE1193044B (de) *	1963-08-05	1965-05-20	Bayer Ag	Verfahren zur Herstellung phosphorylierter Urethane
DE2512375A1 (de) *	1975-03-21	1976-09-30	Bayer Ag	1-hydroxy-2,2,2-trichloraethan- thionophosphonsaeuredialkylester, verfahren zu ihrer herstellung sowie ihre verwendung als insektizide
US4950658A (en) *	1988-12-06	1990-08-21	Board Of Trustees Of Southern Illinois Univ.	Method of medical treatment of Alzheimer's disease

1996
- 1996-04-25 DE DE19616471A patent/DE19616471A1/de not_active Withdrawn
1997
- 1997-04-17 BR BR9709300A patent/BR9709300A/pt not_active Application Discontinuation
- 1997-04-17 EP EP97920431A patent/EP0896540A1/en not_active Withdrawn
- 1997-04-17 PL PL97333464A patent/PL333464A1/xx unknown
- 1997-04-17 HU HU9903366A patent/HUP9903366A3/hu unknown
- 1997-04-17 AU AU24623/97A patent/AU2462397A/en not_active Abandoned
- 1997-04-17 SK SK1463-98A patent/SK146398A3/sk unknown
- 1997-04-17 TR TR1998/02137T patent/TR199802137T2/xx unknown
- 1997-04-17 WO PCT/US1997/006469 patent/WO1997039756A1/en not_active Ceased
- 1997-04-17 JP JP09538197A patent/JP2000510455A/ja active Pending
- 1997-04-17 CZ CZ983434A patent/CZ343498A3/cs unknown
- 1997-04-17 KR KR1019980708502A patent/KR20000010611A/ko not_active Withdrawn
- 1997-04-17 IL IL12669897A patent/IL126698A0/xx unknown
- 1997-04-17 CA CA002252567A patent/CA2252567A1/en not_active Abandoned
- 1997-04-24 ID IDP971362A patent/ID16678A/id unknown
- 1997-04-24 ZA ZA9703538A patent/ZA973538B/xx unknown
- 1997-04-25 AR ARP970101724A patent/AR006870A1/es unknown
1998
- 1998-10-22 BG BG102864A patent/BG102864A/xx unknown
- 1998-10-23 NO NO984964A patent/NO984964L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
WO1997039756A1 (en)	1997-10-30
HUP9903366A2 (en)	2000-07-28
CA2252567A1 (en)	1997-10-30
ZA973538B (en)	1997-11-18
IL126698A0 (en)	1999-08-17
BR9709300A (pt)	1999-08-10
DE19616471A1 (de)	1997-10-30
EP0896540A1 (en)	1999-02-17
NO984964L (no)	1998-12-22
JP2000510455A (ja)	2000-08-15
CZ343498A3 (cs)	1999-02-17
BG102864A (en)	1999-09-30
PL333464A1 (en)	1999-12-20
HUP9903366A3 (en)	2000-08-28
AR006870A1 (es)	1999-09-29
AU2462397A (en)	1997-11-12
TR199802137T2 (xx)	1999-02-22
KR20000010611A (ko)	2000-02-25
NO984964D0 (no)	1998-10-23
ID16678A (id)	1997-10-30

Publication	Publication Date	Title
EA005852B1 (ru)	2005-06-30	ПИРРОЛО[2,3-d]ПИРИМИДИНЫ
JPH0662414B2 (ja)	1994-08-17	アリールアミドアザビシクロアルカンを含む記憶増強または記憶欠損矯正用組成物
JP2009263377A (ja)	2009-11-12	カリウムチャネルモジュレーター
FR2606018A1 (fr)	1988-05-06	Nouveaux a-aminoacides substitues, leur preparation et leur utilisation en therapeutique comme medicaments
CA1130308A (en)	1982-08-24	Preparation of cyclopropane carboxylic acids and esters
KR20150011003A (ko)	2015-01-29	Lpar 길항제로서 치환된 피라졸 화합물
NO315373B1 (no)	2003-08-25	Spirosykliske metallprotease-inhibitorer
NO177711B (no)	1995-07-31	Analogifremgangsmåte for fremstilling av terapautisk aktive azabicyklo- og azacyklo- oksimer og -aminer
NO147104B (no)	1982-10-25	Analogifremgangsmaate ved fremstilling av terapeutisk aktive acetylenderivater av aminosyrer
CA2207429A1 (en)	1996-06-20	Polyarylcarbamoylaza - and - carbamoylalkanedioic acids
JP2005514454A6 (ja)	2005-08-04	カリウムチャネルモジュレーター
WO1979000427A1 (en)	1979-07-12	Herbicidal pyridine derivative
NO170976B (no)	1992-09-28	Analogifremgangsmaate for fremstilling av terapeutisk aktive fenylbuten-syrederivater
SK146398A3 (en)	1999-06-11	Use of phosphonic acid esters for the treatment of functional disorders of the brain and depression
MXPA98008643A (en)	1999-09-01	Use of phosphonic acid esters for the treatment of functional transtornes of the brain and the depression
GB2145085A (en)	1985-03-20	Herbicidal 2-and/or 6-fluoromethyl-dihydropyridine-3,5-dicarboxylic acid esters
RU2010794C1 (ru)	1994-04-15	Производные циклического амида или их фармакологически приемлемая соль, обладающая антиацетилхолинэстеродной активностью
FI97231B (fi)	1996-07-31	Menetelmä 4-substituoitujen 2-aminoalk-3-eenihappojen valmistamiseksi
EP0183174B1 (en)	1988-10-26	Substituted phenoxy urea, processes for its preparation and herbicide containing it as active ingredient
US5082964A (en)	1992-01-21	Selective acetylcholinesterase inhibitors and methods of making and using same
US20080032950A1 (en)	2008-02-07	Neurologically-Active Compounds
US20170233339A1 (en)	2017-08-17	Heterocyclic compound
CS220713B1 (cs)	1983-04-29	Dialkylestery kyseliny p-toluensulfonyloxymethanfosfonové a způsob jejich přípravy
DE3121189A1 (de)	1982-02-25	"n-substituierte mercaptoacylpropionamide"
JPH0395143A (ja)	1991-04-19	アミノケトン誘導体