IL94779A - Aromatic fluorooctones containing yarnsProcessing process and acetylcholinesterase inhibitors containing them - Google Patents
Aromatic fluorooctones containing yarnsProcessing process and acetylcholinesterase inhibitors containing themInfo
- Publication number
- IL94779A IL94779A IL9477990A IL9477990A IL94779A IL 94779 A IL94779 A IL 94779A IL 9477990 A IL9477990 A IL 9477990A IL 9477990 A IL9477990 A IL 9477990A IL 94779 A IL94779 A IL 94779A
- Authority
- IL
- Israel
- Prior art keywords
- compound
- chg
- alkyl
- formula
- compounds
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 73
- 239000000203 mixture Substances 0.000 title claims description 43
- 108010022752 Acetylcholinesterase Proteins 0.000 title claims description 9
- 229940022698 acetylcholinesterase Drugs 0.000 title claims description 9
- 230000002401 inhibitory effect Effects 0.000 title claims description 8
- 102100033639 Acetylcholinesterase Human genes 0.000 title description 7
- 238000002360 preparation method Methods 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims description 210
- -1 5- octyl Chemical group 0.000 claims description 63
- 238000006243 chemical reaction Methods 0.000 claims description 58
- 125000000217 alkyl group Chemical group 0.000 claims description 37
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 230000007062 hydrolysis Effects 0.000 claims description 14
- 238000006460 hydrolysis reaction Methods 0.000 claims description 14
- 150000001266 acyl halides Chemical class 0.000 claims description 12
- 150000002148 esters Chemical class 0.000 claims description 12
- 208000024827 Alzheimer disease Diseases 0.000 claims description 10
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 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 description 6
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 6
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 5
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 5
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 101100134929 Gallus gallus COR9 gene Proteins 0.000 claims description 4
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 claims description 3
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 3
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 230000001590 oxidative effect Effects 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- 239000004480 active ingredient Substances 0.000 claims 3
- 102000012440 Acetylcholinesterase Human genes 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- 101100516554 Caenorhabditis elegans nhr-5 gene Proteins 0.000 claims 1
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims 1
- 150000001718 carbodiimides Chemical class 0.000 claims 1
- 230000003301 hydrolyzing effect Effects 0.000 claims 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 claims 1
- 102200130520 rs121907896 Human genes 0.000 claims 1
- 208000024891 symptom Diseases 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 161
- 229960004132 diethyl ether Drugs 0.000 description 50
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 38
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- 239000000243 solution Substances 0.000 description 33
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
- 239000000047 product Substances 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 150000001298 alcohols Chemical class 0.000 description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 16
- 239000012267 brine Substances 0.000 description 16
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 239000002904 solvent Substances 0.000 description 14
- 239000012044 organic layer Substances 0.000 description 13
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 239000010410 layer Substances 0.000 description 10
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 10
- 239000012954 diazonium Substances 0.000 description 9
- 238000004821 distillation Methods 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 9
- 150000002576 ketones Chemical class 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 8
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- 150000001989 diazonium salts Chemical class 0.000 description 8
- 229910052749 magnesium Inorganic materials 0.000 description 8
- 239000011777 magnesium Substances 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical compound CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 6
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 5
- 239000012230 colorless oil Substances 0.000 description 5
- 239000005457 ice water Substances 0.000 description 5
- 125000001544 thienyl group Chemical group 0.000 description 5
- HNFNHSDFQRGCSZ-UHFFFAOYSA-N (3-trimethylsilylphenyl)methanol Chemical compound C[Si](C)(C)C1=CC=CC(CO)=C1 HNFNHSDFQRGCSZ-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 4
- 206010039966 Senile dementia Diseases 0.000 description 4
- STSCVKRWJPWALQ-UHFFFAOYSA-N TRIFLUOROACETIC ACID ETHYL ESTER Chemical compound CCOC(=O)C(F)(F)F STSCVKRWJPWALQ-UHFFFAOYSA-N 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 150000001299 aldehydes Chemical class 0.000 description 4
- 235000019270 ammonium chloride Nutrition 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 229910052744 lithium Inorganic materials 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- FSWNRRSWFBXQCL-UHFFFAOYSA-N (3-bromophenyl)methanol Chemical compound OCC1=CC=CC(Br)=C1 FSWNRRSWFBXQCL-UHFFFAOYSA-N 0.000 description 3
- ZNFLHCKSMCSEGW-UHFFFAOYSA-N 3-trimethylsilylbenzaldehyde Chemical compound C[Si](C)(C)C1=CC=CC(C=O)=C1 ZNFLHCKSMCSEGW-UHFFFAOYSA-N 0.000 description 3
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 3
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 3
- IGVPBCZDHMIOJH-UHFFFAOYSA-N Phenyl butyrate Chemical compound CCCC(=O)OC1=CC=CC=C1 IGVPBCZDHMIOJH-UHFFFAOYSA-N 0.000 description 3
- 229940024606 amino acid Drugs 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- RCBVKBFIWMOMHF-UHFFFAOYSA-L hydroxy-(hydroxy(dioxo)chromio)oxy-dioxochromium;pyridine Chemical compound C1=CC=NC=C1.C1=CC=NC=C1.O[Cr](=O)(=O)O[Cr](O)(=O)=O RCBVKBFIWMOMHF-UHFFFAOYSA-L 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 230000016978 synaptic transmission, cholinergic Effects 0.000 description 3
- GBDYVRYMDFDWCS-UHFFFAOYSA-N (2-bromo-5-methoxyphenyl)-trimethylsilane Chemical compound COC1=CC=C(Br)C([Si](C)(C)C)=C1 GBDYVRYMDFDWCS-UHFFFAOYSA-N 0.000 description 2
- JXQZFRPARQBDKV-UHFFFAOYSA-N (3-bromophenyl)-trimethylsilane Chemical compound C[Si](C)(C)C1=CC=CC(Br)=C1 JXQZFRPARQBDKV-UHFFFAOYSA-N 0.000 description 2
- FAXWFCTVSHEODL-UHFFFAOYSA-N 2,4-dibromophenol Chemical compound OC1=CC=C(Br)C=C1Br FAXWFCTVSHEODL-UHFFFAOYSA-N 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- JJCKHVUTVOPLBV-UHFFFAOYSA-N 3-Methylbenzyl alcohol Chemical compound CC1=CC=CC(CO)=C1 JJCKHVUTVOPLBV-UHFFFAOYSA-N 0.000 description 2
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- PIJVFDBKTWXHHD-UHFFFAOYSA-N Physostigmine Natural products C12=CC(OC(=O)NC)=CC=C2N(C)C2C1(C)CCN2C PIJVFDBKTWXHHD-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 238000006859 Swern oxidation reaction Methods 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- DVPGBDZQQANSLM-UHFFFAOYSA-N [3-(bromomethyl)phenyl]-trimethylsilane Chemical compound C[Si](C)(C)C1=CC=CC(CBr)=C1 DVPGBDZQQANSLM-UHFFFAOYSA-N 0.000 description 2
- ORRFQDARTKAQTO-UHFFFAOYSA-N [3-(trimethylsilylmethyl)phenyl]methanol Chemical compound C[Si](C)(C)CC1=CC=CC(CO)=C1 ORRFQDARTKAQTO-UHFFFAOYSA-N 0.000 description 2
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
- 229960004373 acetylcholine Drugs 0.000 description 2
- 150000001413 amino acids Chemical group 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 238000001311 chemical methods and process Methods 0.000 description 2
- 239000000544 cholinesterase inhibitor Substances 0.000 description 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 2
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 2
- 125000004093 cyano group Chemical group *C#N 0.000 description 2
- FJBFPHVGVWTDIP-UHFFFAOYSA-N dibromomethane Chemical compound BrCBr FJBFPHVGVWTDIP-UHFFFAOYSA-N 0.000 description 2
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 238000004508 fractional distillation Methods 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 2
- 229910001623 magnesium bromide Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- GREQNXBOPYIANC-UHFFFAOYSA-N phenyl butanoate hydrochloride Chemical compound Cl.CCCC(=O)OC1=CC=CC=C1 GREQNXBOPYIANC-UHFFFAOYSA-N 0.000 description 2
- PIJVFDBKTWXHHD-HIFRSBDPSA-N physostigmine Chemical compound C12=CC(OC(=O)NC)=CC=C2N(C)[C@@H]2[C@@]1(C)CCN2C PIJVFDBKTWXHHD-HIFRSBDPSA-N 0.000 description 2
- 229960001697 physostigmine Drugs 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 2
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 2
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N sarcosine Chemical compound C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 235000010288 sodium nitrite Nutrition 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- OKYWWQYKBAFJDE-UHFFFAOYSA-N trimethyl-[3-[3-[3-(3-trimethylsilylphenyl)propoxy]propyl]phenyl]silane Chemical compound C[Si](C)(C)C1=CC=CC(CCCOCCCC=2C=C(C=CC=2)[Si](C)(C)C)=C1 OKYWWQYKBAFJDE-UHFFFAOYSA-N 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- IYKLZBIWFXPUCS-VIFPVBQESA-N (2s)-2-(naphthalen-1-ylamino)propanoic acid Chemical compound C1=CC=C2C(N[C@@H](C)C(O)=O)=CC=CC2=C1 IYKLZBIWFXPUCS-VIFPVBQESA-N 0.000 description 1
- TZFLBWAKFGADPX-UHFFFAOYSA-N (3-bromo-5-trimethylsilylphenyl)-trimethylsilane Chemical compound C[Si](C)(C)C1=CC(Br)=CC([Si](C)(C)C)=C1 TZFLBWAKFGADPX-UHFFFAOYSA-N 0.000 description 1
- SGPDWCOBFRVOGB-UHFFFAOYSA-N (3-bromophenyl)methyl-trimethylsilane Chemical compound C[Si](C)(C)CC1=CC=CC(Br)=C1 SGPDWCOBFRVOGB-UHFFFAOYSA-N 0.000 description 1
- GMVJKSNPLYBFSO-UHFFFAOYSA-N 1,2,3-tribromobenzene Chemical compound BrC1=CC=CC(Br)=C1Br GMVJKSNPLYBFSO-UHFFFAOYSA-N 0.000 description 1
- YWDUZLFWHVQCHY-UHFFFAOYSA-N 1,3,5-tribromobenzene Chemical compound BrC1=CC(Br)=CC(Br)=C1 YWDUZLFWHVQCHY-UHFFFAOYSA-N 0.000 description 1
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- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 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
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 125000001935 tetracenyl group Chemical group C1(=CC=CC2=CC3=CC4=CC=CC=C4C=C3C=C12)* 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- OVMFTFDFVZRFJD-UHFFFAOYSA-N trimethyl-(3-methylphenyl)silane Chemical compound CC1=CC=CC([Si](C)(C)C)=C1 OVMFTFDFVZRFJD-UHFFFAOYSA-N 0.000 description 1
- 239000005051 trimethylchlorosilane Substances 0.000 description 1
- 125000003960 triphenylenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C3=CC=CC=C3C12)* 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
Classifications
-
- 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
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
-
- 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
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Silicates, Zeolites, And Molecular Sieves (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP89401775A EP0403713A1 (en) | 1989-06-22 | 1989-06-22 | Novel acetylcholinesterase inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| IL94779A true IL94779A (en) | 1996-09-12 |
Family
ID=8202963
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL9477990A IL94779A (en) | 1989-06-22 | 1990-06-19 | Aromatic fluorooctones containing yarnsProcessing process and acetylcholinesterase inhibitors containing them |
Country Status (19)
| Country | Link |
|---|---|
| EP (2) | EP0403713A1 (ja) |
| JP (1) | JP2879951B2 (ja) |
| KR (1) | KR0139529B1 (ja) |
| CN (1) | CN1027759C (ja) |
| AR (1) | AR247214A1 (ja) |
| AT (1) | ATE119535T1 (ja) |
| AU (1) | AU626428B2 (ja) |
| CA (1) | CA2019231C (ja) |
| DE (1) | DE69017543T2 (ja) |
| DK (1) | DK0409676T3 (ja) |
| ES (1) | ES2072406T3 (ja) |
| FI (1) | FI97619C (ja) |
| HU (1) | HU210569B (ja) |
| IE (1) | IE66155B1 (ja) |
| IL (1) | IL94779A (ja) |
| NO (1) | NO178374C (ja) |
| NZ (1) | NZ234136A (ja) |
| PT (1) | PT94449B (ja) |
| ZA (1) | ZA904715B (ja) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5523442A (en) * | 1993-02-16 | 1996-06-04 | Merrell Pharmaceuticals Inc. | Silylated acetylcholinesterase inhibitors |
| EP0611769A1 (en) * | 1993-02-16 | 1994-08-24 | Merrell Dow Pharmaceuticals Inc. | Silylated acetylcholinesterase inhibitors |
| EP0627400A1 (en) * | 1993-06-04 | 1994-12-07 | Merrell Dow Pharmaceuticals Inc. | Aromatic acetylcholinesterase inhibitors |
| US5554780A (en) * | 1994-05-05 | 1996-09-10 | Merrell Pharmaceuticals Inc. | Process for the preparation of 1-(3-trialkylsilylphenyl)-2,2,2-trifluoromethyl ethanone derivatives |
| US5486638A (en) * | 1994-11-08 | 1996-01-23 | Marion Merrell Dow Inc. | Process for the preparation of 1-halo-3-trialkysilanyl-benzene derivatives |
| EP0749972A1 (en) * | 1995-06-21 | 1996-12-27 | Merrell Pharmaceuticals Inc. | A process for preparing 1-(3-trialkylsilylphenyl)-2,2,2-trifluoromethyl ethanone derivatives |
| US6673784B1 (en) | 1996-03-19 | 2004-01-06 | G. D. Searle & Co. | Electrophilic ketones for the treatment of herpesvirus infections |
| CN1059702C (zh) * | 1997-12-30 | 2000-12-20 | 中国科学院上海细胞生物学研究所 | 从哺乳类细胞中获得脑型乙酰胆碱酯酶的方法 |
| US6218383B1 (en) | 1998-08-07 | 2001-04-17 | Targacept, Inc. | Pharmaceutical compositions for the prevention and treatment of central nervous system disorders |
| US6084117A (en) * | 1999-11-22 | 2000-07-04 | Albemarle Corporation | Production of silated haloarenes by selective silylation of polyhaloarenes |
| EA037187B1 (ru) | 2010-02-09 | 2021-02-17 | Дзе Джонс Хопкинс Юниверсити | Способ и композиция для лечения когнитивного расстройства |
| US10154988B2 (en) | 2012-11-14 | 2018-12-18 | The Johns Hopkins University | Methods and compositions for treating schizophrenia |
| MX362886B (es) | 2012-12-13 | 2019-02-22 | H Lundbeck As | Composición sinérgica que comprende vortioxetina y donepezilo para incrementar los niveles de acetilcolina en el cerebro, y el uso de la misma en el tratamiento de una disfunción cognitiva. |
| WO2014144801A1 (en) | 2013-03-15 | 2014-09-18 | Agenebio Inc. | Methods and compositions for improving cognitive function |
| WO2014144663A1 (en) | 2013-03-15 | 2014-09-18 | The Johns Hopkins University | Methods and compositions for improving cognitive function |
| US10925834B2 (en) | 2015-05-22 | 2021-02-23 | Agenebio, Inc. | Extended release pharmaceutical compositions of levetiracetam |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL25820A (en) * | 1966-05-22 | 1971-02-25 | Yissum Res Dev Co | Silicon containing beta-hydroxy alpha-phenyl carboxylic acids,their amide and ester derivatives and intermediates for their preparation |
| US4835099A (en) * | 1986-11-20 | 1989-05-30 | Becton, Dickinson And Company | Signal enhancement in immunoassay by modulation of enzymatic catalysis |
-
1989
- 1989-06-22 EP EP89401775A patent/EP0403713A1/en not_active Withdrawn
-
1990
- 1990-06-18 ZA ZA904715A patent/ZA904715B/xx unknown
- 1990-06-18 CA CA002019231A patent/CA2019231C/en not_active Expired - Lifetime
- 1990-06-19 NZ NZ234136A patent/NZ234136A/xx unknown
- 1990-06-19 AU AU57584/90A patent/AU626428B2/en not_active Ceased
- 1990-06-19 IL IL9477990A patent/IL94779A/en not_active IP Right Cessation
- 1990-06-20 ES ES90401745T patent/ES2072406T3/es not_active Expired - Lifetime
- 1990-06-20 DK DK90401745.6T patent/DK0409676T3/da active
- 1990-06-20 AT AT90401745T patent/ATE119535T1/de not_active IP Right Cessation
- 1990-06-20 FI FI903104A patent/FI97619C/fi active IP Right Grant
- 1990-06-20 DE DE69017543T patent/DE69017543T2/de not_active Expired - Lifetime
- 1990-06-20 EP EP90401745A patent/EP0409676B1/en not_active Expired - Lifetime
- 1990-06-20 AR AR90317164A patent/AR247214A1/es active
- 1990-06-20 HU HU903933A patent/HU210569B/hu not_active IP Right Cessation
- 1990-06-21 PT PT94449A patent/PT94449B/pt not_active IP Right Cessation
- 1990-06-21 KR KR1019900009196A patent/KR0139529B1/ko not_active IP Right Cessation
- 1990-06-21 IE IE225290A patent/IE66155B1/en not_active IP Right Cessation
- 1990-06-21 NO NO902776A patent/NO178374C/no not_active IP Right Cessation
- 1990-06-22 CN CN90103127A patent/CN1027759C/zh not_active Expired - Fee Related
- 1990-06-22 JP JP2163002A patent/JP2879951B2/ja not_active Expired - Lifetime
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| KB | Patent renewed | ||
| RH | Patent void | ||
| HC | Change of name of proprietor(s) |
Owner name: AVENTIS INC. Free format text: FORMER NAME:MERRELL PHARMACEUTICALS INC. |