DE69713295T2 - Azabicyclishe carbaniumsaureester zur therapeutsichen verwendung - Google Patents
Azabicyclishe carbaniumsaureester zur therapeutsichen verwendungInfo
- Publication number
- DE69713295T2 DE69713295T2 DE69713295T DE69713295T DE69713295T2 DE 69713295 T2 DE69713295 T2 DE 69713295T2 DE 69713295 T DE69713295 T DE 69713295T DE 69713295 T DE69713295 T DE 69713295T DE 69713295 T2 DE69713295 T2 DE 69713295T2
- Authority
- DE
- Germany
- Prior art keywords
- formula
- azabicyclo
- ester
- octan
- compound
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired - Fee Related
Links
- 230000001225 therapeutic effect Effects 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 102
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 30
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 26
- 239000002253 acid Substances 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 239000001257 hydrogen Substances 0.000 claims description 19
- 239000000203 mixture Substances 0.000 claims description 17
- 238000011282 treatment Methods 0.000 claims description 17
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
- -1 substituents halogen Chemical class 0.000 claims description 13
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 claims description 12
- 239000012442 inert solvent Substances 0.000 claims description 11
- 238000011321 prophylaxis Methods 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 208000035475 disorder Diseases 0.000 claims description 8
- 150000002367 halogens Chemical group 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 7
- 239000003054 catalyst Substances 0.000 claims description 7
- 150000002431 hydrogen Chemical group 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- 229910000085 borane Inorganic materials 0.000 claims description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 6
- 239000012948 isocyanate Substances 0.000 claims description 6
- 229960002715 nicotine Drugs 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- JRNNBGOEDTYSGH-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl n-(3,4-dichlorophenyl)carbamate Chemical compound C1=C(Cl)C(Cl)=CC=C1NC(=O)OC1C(CC2)CCN2C1 JRNNBGOEDTYSGH-UHFFFAOYSA-N 0.000 claims description 5
- SLJMPDGIEKZJAU-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl n-(4-bromophenyl)carbamate Chemical compound C1=CC(Br)=CC=C1NC(=O)OC1C(CC2)CCN2C1 SLJMPDGIEKZJAU-UHFFFAOYSA-N 0.000 claims description 5
- WVQQNNNYMPFHGO-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl n-(4-methylphenyl)carbamate Chemical compound C1=CC(C)=CC=C1NC(=O)OC1C(CC2)CCN2C1 WVQQNNNYMPFHGO-UHFFFAOYSA-N 0.000 claims description 5
- 150000002513 isocyanates Chemical class 0.000 claims description 5
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 4
- JEPJAGMRBZWMCT-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl n-phenylcarbamate Chemical compound C1N(CC2)CCC2C1OC(=O)NC1=CC=CC=C1 JEPJAGMRBZWMCT-UHFFFAOYSA-N 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 208000028017 Psychotic disease Diseases 0.000 claims description 4
- 229910052731 fluorine Chemical group 0.000 claims description 4
- 239000011737 fluorine Chemical group 0.000 claims description 4
- 150000002540 isothiocyanates Chemical class 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 3
- OLMKACMFPQRGRL-UHFFFAOYSA-N 1-azabicyclo[2.2.1]heptan-3-yl n-phenylcarbamate Chemical compound C1N(C2)CCC2C1OC(=O)NC1=CC=CC=C1 OLMKACMFPQRGRL-UHFFFAOYSA-N 0.000 claims description 3
- ONHFLIBNUOFXHA-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl n-(3-methoxyphenyl)carbamate Chemical compound COC1=CC=CC(NC(=O)OC2C3CCN(CC3)C2)=C1 ONHFLIBNUOFXHA-UHFFFAOYSA-N 0.000 claims description 3
- PPPJULCFKXODES-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl n-(4-cyanophenyl)carbamate Chemical compound C1N(CC2)CCC2C1OC(=O)NC1=CC=C(C#N)C=C1 PPPJULCFKXODES-UHFFFAOYSA-N 0.000 claims description 3
- SSLDFEPTWKCCLA-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl n-(4-methoxyphenyl)carbamate Chemical compound C1=CC(OC)=CC=C1NC(=O)OC1C(CC2)CCN2C1 SSLDFEPTWKCCLA-UHFFFAOYSA-N 0.000 claims description 3
- NBDVCMQUQDOFRR-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl n-naphthalen-1-ylcarbamate Chemical compound C1N(CC2)CCC2C1OC(=O)NC1=CC=CC2=CC=CC=C12 NBDVCMQUQDOFRR-UHFFFAOYSA-N 0.000 claims description 3
- RYDWZFYEYKGKQN-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl n-pyridin-2-ylcarbamate Chemical compound C1N(CC2)CCC2C1OC(=O)NC1=CC=CC=N1 RYDWZFYEYKGKQN-UHFFFAOYSA-N 0.000 claims description 3
- IVUHKEGDYXRUHB-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl n-pyridin-4-ylcarbamate Chemical compound C1N(CC2)CCC2C1OC(=O)NC1=CC=NC=C1 IVUHKEGDYXRUHB-UHFFFAOYSA-N 0.000 claims description 3
- SOGRRKOWZXEBMI-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl n-quinolin-3-ylcarbamate Chemical compound C1N(CC2)CCC2C1OC(=O)NC1=CN=C(C=CC=C2)C2=C1 SOGRRKOWZXEBMI-UHFFFAOYSA-N 0.000 claims description 3
- 208000019901 Anxiety disease Diseases 0.000 claims description 3
- 208000028698 Cognitive impairment Diseases 0.000 claims description 3
- 208000018737 Parkinson disease Diseases 0.000 claims description 3
- 208000000323 Tourette Syndrome Diseases 0.000 claims description 3
- 208000016620 Tourette disease Diseases 0.000 claims description 3
- JEPJAGMRBZWMCT-ZDUSSCGKSA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] n-phenylcarbamate Chemical compound O([C@@H]1C2CCN(CC2)C1)C(=O)NC1=CC=CC=C1 JEPJAGMRBZWMCT-ZDUSSCGKSA-N 0.000 claims description 3
- JEPJAGMRBZWMCT-CYBMUJFWSA-N [(3s)-1-azabicyclo[2.2.2]octan-3-yl] n-phenylcarbamate Chemical compound O([C@H]1C2CCN(CC2)C1)C(=O)NC1=CC=CC=C1 JEPJAGMRBZWMCT-CYBMUJFWSA-N 0.000 claims description 3
- UKLDJPRMSDWDSL-UHFFFAOYSA-L [dibutyl(dodecanoyloxy)stannyl] dodecanoate Chemical compound CCCCCCCCCCCC(=O)O[Sn](CCCC)(CCCC)OC(=O)CCCCCCCCCCC UKLDJPRMSDWDSL-UHFFFAOYSA-L 0.000 claims description 3
- 230000036506 anxiety Effects 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 208000010877 cognitive disease Diseases 0.000 claims description 3
- 239000012975 dibutyltin dilaurate Substances 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 230000004064 dysfunction Effects 0.000 claims description 3
- OVPWBKSJYFYQPC-UHFFFAOYSA-N o-(1-azabicyclo[2.2.2]octan-3-yl) n-phenylcarbamothioate Chemical compound C1N(CC2)CCC2C1OC(=S)NC1=CC=CC=C1 OVPWBKSJYFYQPC-UHFFFAOYSA-N 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 201000000980 schizophrenia Diseases 0.000 claims description 3
- 230000005586 smoking cessation Effects 0.000 claims description 3
- 208000000044 Amnesia Diseases 0.000 claims description 2
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 2
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 2
- 206010003805 Autism Diseases 0.000 claims description 2
- 208000020706 Autistic disease Diseases 0.000 claims description 2
- 208000020925 Bipolar disease Diseases 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 2
- 208000019888 Circadian rhythm sleep disease Diseases 0.000 claims description 2
- 208000023105 Huntington disease Diseases 0.000 claims description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 2
- 208000001456 Jet Lag Syndrome Diseases 0.000 claims description 2
- 206010026749 Mania Diseases 0.000 claims description 2
- 208000026139 Memory disease Diseases 0.000 claims description 2
- 206010057852 Nicotine dependence Diseases 0.000 claims description 2
- 208000025569 Tobacco Use disease Diseases 0.000 claims description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 2
- 208000028683 bipolar I disease Diseases 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 230000001713 cholinergic effect Effects 0.000 claims description 2
- 208000033915 jet lag type circadian rhythm sleep disease Diseases 0.000 claims description 2
- 201000003723 learning disability Diseases 0.000 claims description 2
- 230000006984 memory degeneration Effects 0.000 claims description 2
- 208000023060 memory loss Diseases 0.000 claims description 2
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 2
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 2
- 230000036407 pain Effects 0.000 claims description 2
- 208000027753 pain disease Diseases 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- 239000007787 solid Substances 0.000 description 32
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 26
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
- 238000000034 method Methods 0.000 description 20
- IVLICPVPXWEGCA-UHFFFAOYSA-N 3-quinuclidinol Chemical compound C1C[C@@H]2C(O)C[N@]1CC2 IVLICPVPXWEGCA-UHFFFAOYSA-N 0.000 description 15
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 150000002148 esters Chemical class 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 12
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 description 11
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 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 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
- 235000019341 magnesium sulphate Nutrition 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 230000027455 binding Effects 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 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 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000006260 foam Substances 0.000 description 4
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 235000017550 sodium carbonate Nutrition 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 229920002873 Polyethylenimine Polymers 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 229940098773 bovine serum albumin Drugs 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 3
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 2
- SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 description 2
- ULHIMEHJZGFPKJ-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl n-(2-fluorophenyl)carbamate Chemical compound FC1=CC=CC=C1NC(=O)OC1C(CC2)CCN2C1 ULHIMEHJZGFPKJ-UHFFFAOYSA-N 0.000 description 2
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 101000783401 Bungarus multicinctus Alpha-bungarotoxin Proteins 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 201000006347 Intellectual Disability Diseases 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 102000015296 acetylcholine-gated cation-selective channel activity proteins Human genes 0.000 description 2
- 108040006409 acetylcholine-gated cation-selective channel activity proteins Proteins 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 235000011148 calcium chloride Nutrition 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 239000002026 chloroform extract Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000003365 glass fiber Substances 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000003456 ion exchange resin Substances 0.000 description 2
- 229920003303 ion-exchange polymer Polymers 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000003589 local anesthetic agent Substances 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- QKFJKGMPGYROCL-UHFFFAOYSA-N phenyl isothiocyanate Chemical compound S=C=NC1=CC=CC=C1 QKFJKGMPGYROCL-UHFFFAOYSA-N 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 125000005270 trialkylamine group Chemical group 0.000 description 2
- IVLICPVPXWEGCA-ZETCQYMHSA-N (3r)-1-azabicyclo[2.2.2]octan-3-ol Chemical compound C1CC2[C@@H](O)CN1CC2 IVLICPVPXWEGCA-ZETCQYMHSA-N 0.000 description 1
- IVLICPVPXWEGCA-SSDOTTSWSA-N (3s)-1-azabicyclo[2.2.2]octan-3-ol Chemical compound C1CC2[C@H](O)CN1CC2 IVLICPVPXWEGCA-SSDOTTSWSA-N 0.000 description 1
- 229930182840 (S)-nicotine Natural products 0.000 description 1
- YPWZLBKKVGKDSH-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl n-(3-bromophenyl)carbamate Chemical compound BrC1=CC=CC(NC(=O)OC2C3CCN(CC3)C2)=C1 YPWZLBKKVGKDSH-UHFFFAOYSA-N 0.000 description 1
- WQFYZFPLEQADRM-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl n-(3-chloro-4-fluorophenyl)carbamate Chemical compound C1=C(Cl)C(F)=CC=C1NC(=O)OC1C(CC2)CCN2C1 WQFYZFPLEQADRM-UHFFFAOYSA-N 0.000 description 1
- QCWZYJPDPROWAC-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl n-(3-chlorophenyl)carbamate Chemical compound ClC1=CC=CC(NC(=O)OC2C3CCN(CC3)C2)=C1 QCWZYJPDPROWAC-UHFFFAOYSA-N 0.000 description 1
- NXQPDZKERDRSRL-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl n-(3-fluorophenyl)carbamate Chemical compound FC1=CC=CC(NC(=O)OC2C3CCN(CC3)C2)=C1 NXQPDZKERDRSRL-UHFFFAOYSA-N 0.000 description 1
- WIXYVZUUXMTNBY-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl n-(4-chloro-3-fluorophenyl)carbamate Chemical compound C1=C(Cl)C(F)=CC(NC(=O)OC2C3CCN(CC3)C2)=C1 WIXYVZUUXMTNBY-UHFFFAOYSA-N 0.000 description 1
- KHINMWCEXQIYHR-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl n-(4-chlorophenyl)carbamate Chemical compound C1=CC(Cl)=CC=C1NC(=O)OC1C(CC2)CCN2C1 KHINMWCEXQIYHR-UHFFFAOYSA-N 0.000 description 1
- RUQCFKNORLVKCA-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl n-(4-fluorophenyl)carbamate Chemical compound C1=CC(F)=CC=C1NC(=O)OC1C(CC2)CCN2C1 RUQCFKNORLVKCA-UHFFFAOYSA-N 0.000 description 1
- CZQIJQFTRGDODI-UHFFFAOYSA-N 1-bromo-4-isocyanatobenzene Chemical compound BrC1=CC=C(N=C=O)C=C1 CZQIJQFTRGDODI-UHFFFAOYSA-N 0.000 description 1
- VZNCSZQPNIEEMN-UHFFFAOYSA-N 1-fluoro-2-isocyanatobenzene Chemical compound FC1=CC=CC=C1N=C=O VZNCSZQPNIEEMN-UHFFFAOYSA-N 0.000 description 1
- NPOVTGVGOBJZPY-UHFFFAOYSA-N 1-isocyanato-3-methoxybenzene Chemical compound COC1=CC=CC(N=C=O)=C1 NPOVTGVGOBJZPY-UHFFFAOYSA-N 0.000 description 1
- FMDGXCSMDZMDHZ-UHFFFAOYSA-N 1-isocyanato-4-methoxybenzene Chemical compound COC1=CC=C(N=C=O)C=C1 FMDGXCSMDZMDHZ-UHFFFAOYSA-N 0.000 description 1
- BDQNKCYCTYYMAA-UHFFFAOYSA-N 1-isocyanatonaphthalene Chemical compound C1=CC=C2C(N=C=O)=CC=CC2=C1 BDQNKCYCTYYMAA-UHFFFAOYSA-N 0.000 description 1
- GXVUZYLYWKWJIM-UHFFFAOYSA-N 2-(2-aminoethoxy)ethanamine Chemical compound NCCOCCN GXVUZYLYWKWJIM-UHFFFAOYSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- MFUVCHZWGSJKEQ-UHFFFAOYSA-N 3,4-dichlorphenylisocyanate Chemical compound ClC1=CC=C(N=C=O)C=C1Cl MFUVCHZWGSJKEQ-UHFFFAOYSA-N 0.000 description 1
- SVNCRRZKBNSMIV-UHFFFAOYSA-N 3-Aminoquinoline Chemical compound C1=CC=CC2=CC(N)=CN=C21 SVNCRRZKBNSMIV-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- MUNOBADFTHUUFG-UHFFFAOYSA-N 3-phenylaniline Chemical group NC1=CC=CC(C=2C=CC=CC=2)=C1 MUNOBADFTHUUFG-UHFFFAOYSA-N 0.000 description 1
- YBAZINRZQSAIAY-UHFFFAOYSA-N 4-aminobenzonitrile Chemical compound NC1=CC=C(C#N)C=C1 YBAZINRZQSAIAY-UHFFFAOYSA-N 0.000 description 1
- MGYGFNQQGAQEON-UHFFFAOYSA-N 4-tolyl isocyanate Chemical compound CC1=CC=C(N=C=O)C=C1 MGYGFNQQGAQEON-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 229930003347 Atropine Natural products 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 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
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical class OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 201000004311 Gilles de la Tourette syndrome Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 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 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
- 229960000396 atropine Drugs 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000012267 brine Substances 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
- 238000004364 calculation method Methods 0.000 description 1
- AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical compound [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 description 1
- 229960004484 carbachol Drugs 0.000 description 1
- 150000001715 carbamic acids Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 230000006949 cholinergic function Effects 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000006165 cyclic alkyl group Chemical group 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- MUCZHBLJLSDCSD-UHFFFAOYSA-N diisopropyl fluorophosphate Chemical compound CC(C)OP(F)(=O)OC(C)C MUCZHBLJLSDCSD-UHFFFAOYSA-N 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229960005051 fluostigmine Drugs 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 125000005241 heteroarylamino group Chemical group 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 239000011539 homogenization buffer Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 238000005649 metathesis reaction Methods 0.000 description 1
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 description 1
- 239000000472 muscarinic agonist Substances 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000004112 neuroprotection Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 229940117953 phenylisothiocyanate Drugs 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 239000004149 tartrazine Substances 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
- A61P25/14—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
- A61P25/24—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
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
-
- 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
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/027—Organoboranes and organoborohydrides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Neurosurgery (AREA)
- Veterinary Medicine (AREA)
- Psychiatry (AREA)
- Addiction (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9600683A SE9600683D0 (sv) | 1996-02-23 | 1996-02-23 | Azabicyclic esters of carbamic acids useful in therapy |
| PCT/SE1997/000294 WO1997030998A1 (en) | 1996-02-23 | 1997-02-21 | Azabicyclic esters of carbamic acids useful in therapy |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69713295D1 DE69713295D1 (de) | 2002-07-18 |
| DE69713295T2 true DE69713295T2 (de) | 2003-01-09 |
Family
ID=20401517
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69713295T Expired - Fee Related DE69713295T2 (de) | 1996-02-23 | 1997-02-21 | Azabicyclishe carbaniumsaureester zur therapeutsichen verwendung |
Country Status (26)
| Country | Link |
|---|---|
| US (2) | US5998429A (enExample) |
| EP (1) | EP0885221B1 (enExample) |
| JP (1) | JP2000505452A (enExample) |
| KR (1) | KR19990087184A (enExample) |
| CN (1) | CN1063749C (enExample) |
| AR (1) | AR005876A1 (enExample) |
| AT (1) | ATE219081T1 (enExample) |
| AU (1) | AU706944B2 (enExample) |
| BR (1) | BR9707616A (enExample) |
| CA (1) | CA2246051A1 (enExample) |
| CZ (1) | CZ289110B6 (enExample) |
| DE (1) | DE69713295T2 (enExample) |
| EE (1) | EE9800250A (enExample) |
| HU (1) | HUP9901273A3 (enExample) |
| ID (1) | ID15969A (enExample) |
| IL (2) | IL125620A (enExample) |
| IS (1) | IS4830A (enExample) |
| NO (1) | NO983711L (enExample) |
| NZ (1) | NZ331145A (enExample) |
| PL (1) | PL328614A1 (enExample) |
| RU (1) | RU2172739C2 (enExample) |
| SE (1) | SE9600683D0 (enExample) |
| SK (1) | SK102798A3 (enExample) |
| TR (1) | TR199801642T2 (enExample) |
| WO (1) | WO1997030998A1 (enExample) |
| ZA (1) | ZA971082B (enExample) |
Families Citing this family (131)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5977144A (en) * | 1992-08-31 | 1999-11-02 | University Of Florida | Methods of use and compositions for benzylidene- and cinnamylidene-anabaseines |
| US7214686B2 (en) | 1997-06-30 | 2007-05-08 | Targacept, Inc. | Pharmaceutical compositions and methods for effecting dopamine release |
| US6632823B1 (en) * | 1997-12-22 | 2003-10-14 | Merck & Co., Inc. | Substituted pyridine compounds useful as modulators of acetylcholine receptors |
| US6277870B1 (en) | 1998-05-04 | 2001-08-21 | Astra Ab | Use |
| FR2804430B1 (fr) * | 2000-01-28 | 2002-03-22 | Sanofi Synthelabo | Derives de 4-heteroaryl-1,4-diazabicyclo[3.2.2] nonane, leur preparation et leur application en therapeutique |
| GB0010955D0 (en) | 2000-05-05 | 2000-06-28 | Novartis Ag | Organic compounds |
| US8914114B2 (en) | 2000-05-23 | 2014-12-16 | The Feinstein Institute For Medical Research | Inhibition of inflammatory cytokine production by cholinergic agonists and vagus nerve stimulation |
| AU2001284645A1 (en) * | 2000-08-18 | 2002-03-04 | Pharmacia And Upjohn Company | Quinuclidine-substituted aryl compounds for treatment of disease |
| AU2001282873A1 (en) | 2000-08-18 | 2002-03-04 | Pharmacia And Upjohn Company | Quinuclidine-substituted aryl compounds for treatment of disease |
| US6479510B2 (en) | 2000-08-18 | 2002-11-12 | Pharmacia & Upjohn Company | Quinuclidine-substituted aryl compounds for treatment of disease |
| US6492385B2 (en) | 2000-08-18 | 2002-12-10 | Pharmacia & Upjohn Company | Quinuclidine-substituted heteroaryl moieties for treatment of disease |
| US6500840B2 (en) | 2000-08-21 | 2002-12-31 | Pharmacia & Upjohn Company | Quinuclidine-substituted heteroaryl moieties for treatment of disease |
| WO2002016355A2 (en) * | 2000-08-21 | 2002-02-28 | Pharmacia & Upjohn Company | Quinuclidine-substituted heteroaryl moieties for treatment of disease (nicotinic) acetylcholine receptor ligands |
| AU2001284646A1 (en) * | 2000-08-21 | 2002-03-04 | Pharmacia And Upjohn Company | Quinuclidine-substituted heteroaryl moieties for treatment of disease |
| PE20021019A1 (es) | 2001-04-19 | 2002-11-13 | Upjohn Co | Grupos azabiciclicos sustituidos |
| AR036041A1 (es) * | 2001-06-12 | 2004-08-04 | Upjohn Co | Compuestos aromaticos heterociclicos sustituidos con quinuclidina y composiciones farmaceuticas que los contienen |
| AR036040A1 (es) | 2001-06-12 | 2004-08-04 | Upjohn Co | Compuestos de heteroarilo multiciclicos sustituidos con quinuclidinas y composiciones farmaceuticas que los contienen |
| US6562816B2 (en) | 2001-08-24 | 2003-05-13 | Pharmacia & Upjohn Company | Substituted-heteroaryl-7-aza[2.2.1]bicycloheptanes for the treatment of disease |
| CA2455773A1 (en) * | 2001-08-24 | 2003-03-06 | Pharmacia & Upjohn Company | Substituted-aryl 7-aza¬2.2.1|bicycloheptanes for the treatment of disease |
| BR0212477A (pt) * | 2001-09-12 | 2004-08-24 | Upjohn Co | 7-aza[2.2.1] bicicloheptanos substituìdos para o tratamento de doenças |
| MXPA04003007A (es) * | 2001-10-02 | 2004-07-15 | Upjohn Co | Compuestos azabiciclico sustituidos condensados con heteroarilo para el tratamiento de enfermedades. |
| US6849620B2 (en) | 2001-10-26 | 2005-02-01 | Pfizer Inc | N-(azabicyclo moieties)-substituted hetero-bicyclic aromatic compounds for the treatment of disease |
| MXPA04004464A (es) | 2001-11-08 | 2004-08-11 | Upjohn Co | Compuestos de heteroarilo sustituido con azabiciclo para el tratamiento de enfermedades. |
| WO2003042210A1 (en) * | 2001-11-09 | 2003-05-22 | Pharmacia & Upjohn Company | Azabicyclic-phenyl-fused-heterocyclic compounds and their use as alpha7 nachr ligands |
| PL374384A1 (en) | 2001-12-14 | 2005-10-17 | Targacept, Inc. | Methods and compositions for treatment of central nervous system disorders |
| DE10164139A1 (de) | 2001-12-27 | 2003-07-10 | Bayer Ag | 2-Heteroarylcarbonsäureamide |
| US6852716B2 (en) | 2002-02-15 | 2005-02-08 | Pfizer Inc | Substituted-aryl compounds for treatment of disease |
| WO2003070732A1 (en) * | 2002-02-19 | 2003-08-28 | Pharmacia & Upjohn Company | Fused bicyclic-n-bridged-heteroaromatic carboxamides for the treatment of disease |
| WO2003070731A2 (en) * | 2002-02-19 | 2003-08-28 | Pharmacia & Upjohn Company | Azabicyclic compounds for the treatment of disease |
| EP1478646A1 (en) * | 2002-02-20 | 2004-11-24 | PHARMACIA & UPJOHN COMPANY | Azabicyclic compounds with alfa7 nicotinic acetylcholine receptor activity |
| DE10211416A1 (de) * | 2002-03-15 | 2003-09-25 | Bayer Ag | Essig- und Propionsäureamide |
| DE10211415A1 (de) * | 2002-03-15 | 2003-09-25 | Bayer Ag | Bicyclische N-Biarylamide |
| US7176198B2 (en) | 2002-08-01 | 2007-02-13 | Pfizer Inc. | 1H-pyrazole and 1H-pyrrole-azabicyclic compounds for the treatment of disease |
| EP2298759A1 (en) | 2002-08-30 | 2011-03-23 | Memory Pharmaceuticals Corporation | Anabaseine derivatives useful in the treatment of neurodegenerative diseases |
| GB0220581D0 (en) | 2002-09-04 | 2002-10-09 | Novartis Ag | Organic Compound |
| PL210065B1 (pl) | 2002-09-25 | 2011-11-30 | Memory Pharm Corp | Związki indazole, benzotiazole i benzoizotiazole, kompozycje farmaceutyczne je zawierające oraz zastosowanie związków |
| JP2006506395A (ja) * | 2002-11-01 | 2006-02-23 | ファルマシア・アンド・アップジョン・カンパニー・エルエルシー | ＣＮＳ疾患の治療のための、α７ニコチンアゴニスト活性及び５ＨＴ３アンタゴニスト活性を有する化合物 |
| US7238715B2 (en) * | 2002-12-06 | 2007-07-03 | The Feinstein Institute For Medical Research | Treatment of pancreatitis using alpha 7 receptor-binding cholinergic agonists |
| CN102657651A (zh) * | 2002-12-06 | 2012-09-12 | 范因斯坦医学研究院 | 用α 7受体结合胆碱能激动剂抑制炎症 |
| EP1611128A2 (en) * | 2003-03-28 | 2006-01-04 | Pharmacia & Upjohn Company LLC | Positive allosteric modulators of the nicotinic acetylcholine receptor |
| GB0310867D0 (en) | 2003-05-12 | 2003-06-18 | Novartis Ag | Organic compounds |
| DE10334724A1 (de) | 2003-07-30 | 2005-02-24 | Bayer Healthcare Ag | N-Biarylamide |
| PT1678172E (pt) | 2003-10-15 | 2010-03-03 | Targacept Inc | Composições farmacêuticas e métodos para alívio da dor e tratamento de perturbações do sistema nervoso central |
| FR2861076B1 (fr) * | 2003-10-17 | 2006-01-06 | Sanofi Synthelabo | Derives de n-heterocyclymethylbenzamide, leur preparation et leur application en therapeutique |
| US20050137217A1 (en) * | 2003-12-22 | 2005-06-23 | Jianguo Ji | Spirocyclic quinuclidinic ether derivatives |
| BRPI0417323A (pt) | 2003-12-22 | 2007-03-27 | Memory Pharm Corp | indóis, 1h-indazóis, 1,2-benzisoxazóis, e 1,2-benzisotiazóis, composto, composição farmacêutica e usos dos mesmos |
| FR2865208B1 (fr) * | 2004-01-16 | 2009-01-16 | Sanofi Synthelabo | Derives de 1,4-diazabicyclo[3.2.1]octanecarboxmique, leur preparation et leur application en therapeutique |
| US10912712B2 (en) | 2004-03-25 | 2021-02-09 | The Feinstein Institutes For Medical Research | Treatment of bleeding by non-invasive stimulation |
| CA2560741C (en) | 2004-03-25 | 2013-08-06 | Memory Pharmaceuticals Corporation | Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, and preparation and uses thereof |
| JP2007534692A (ja) | 2004-04-22 | 2007-11-29 | メモリー・ファーマシューティカルズ・コーポレイション | インドール、１ｈ−インダゾール、１，２−ベンズイソキサゾール、１，２−ベンゾイソチアゾール、ならびにその調製および使用 |
| DE602005027452D1 (de) | 2004-05-07 | 2011-05-26 | Memory Pharm Corp | 1h-indazole, benzothiazole, 1,2-benzisoxazole, 1,2-benzisothiazole und chromone und deren herstellung und verwendungen |
| PE20060437A1 (es) | 2004-06-18 | 2006-06-08 | Novartis Ag | COMPUESTOS AZA-BICICLONONANOS COMO LIGANDOS COLINERGICOS DE nAChR |
| GB0415746D0 (en) | 2004-07-14 | 2004-08-18 | Novartis Ag | Organic compounds |
| GB0424564D0 (en) * | 2004-11-05 | 2004-12-08 | Novartis Ag | Organic compounds |
| AU2005319248A1 (en) | 2004-12-22 | 2006-06-29 | Memory Pharmaceuticals Corporation | Nicotinic alpha-7 receptor ligands and preparation and uses thereof |
| US11207518B2 (en) | 2004-12-27 | 2021-12-28 | The Feinstein Institutes For Medical Research | Treating inflammatory disorders by stimulation of the cholinergic anti-inflammatory pathway |
| DE602005025020D1 (de) | 2004-12-27 | 2011-01-05 | The Feinstein Inst Medical Res | Behandlung von entzündlichen erkrankungen durch el |
| US7732607B2 (en) | 2005-08-22 | 2010-06-08 | Anatoly Mazurov | Heteroaryl-substituted diazatricycloalkanes and methods of use thereof |
| US8106066B2 (en) | 2005-09-23 | 2012-01-31 | Memory Pharmaceuticals Corporation | Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, pyrazolopyridines, isothiazolopyridines, and preparation and uses thereof |
| GB0521508D0 (en) | 2005-10-21 | 2005-11-30 | Novartis Ag | Organic compounds |
| US8316104B2 (en) | 2005-11-15 | 2012-11-20 | California Institute Of Technology | Method and apparatus for collaborative system |
| GB0525672D0 (en) | 2005-12-16 | 2006-01-25 | Novartis Ag | Organic compounds |
| GB0525673D0 (en) | 2005-12-16 | 2006-01-25 | Novartis Ag | Organic compounds |
| TWI405763B (zh) * | 2006-11-02 | 2013-08-21 | Targacept Inc | 菸鹼乙醯膽鹼受體亞型選擇性之二氮雜雙環烷類醯胺 |
| CL2008000119A1 (es) | 2007-01-16 | 2008-05-16 | Wyeth Corp | Compuestos derivados de pirazol, antagonistas del receptor nicotinico de acetilcolina; composicion farmaceutica; y uso en el tratamiento de enfermedades tales como demencia senil, alzheimer y esquizofrenia. |
| US8367696B2 (en) | 2007-02-09 | 2013-02-05 | Astellas Pharma Inc. | Aza-bridged-ring compound |
| WO2009013535A1 (en) * | 2007-07-23 | 2009-01-29 | Astrazeneca Ab | 2-azabicyclo(2.2.2)octane derivatives as modulators of the glycine transporter i receptor |
| SA08290475B1 (ar) | 2007-08-02 | 2013-06-22 | Targacept Inc | (2s، 3r)-n-(2-((3-بيردينيل)ميثيل)-1-آزا بيسيكلو[2، 2، 2]أوكت-3-يل)بنزو فيوران-2-كربوكساميد، وصور أملاحه الجديدة وطرق استخدامه |
| US8391970B2 (en) | 2007-08-27 | 2013-03-05 | The Feinstein Institute For Medical Research | Devices and methods for inhibiting granulocyte activation by neural stimulation |
| DE602008005928D1 (de) | 2007-10-01 | 2011-05-12 | Comentis Inc | 1h-indol-3-carbonsäure-chinuclidin-4-ylmethylesterderivate als liganden für den nikotinischen alpha-7-acetylcholinrezeptor zur behandlung von alzheimer-krankheit |
| EP2633868A1 (en) | 2008-02-13 | 2013-09-04 | Targacept, Inc. | Combination of alpha 7 nicotinic agonists and antipsychotics |
| US9211409B2 (en) | 2008-03-31 | 2015-12-15 | The Feinstein Institute For Medical Research | Methods and systems for reducing inflammation by neuromodulation of T-cell activity |
| US9662490B2 (en) | 2008-03-31 | 2017-05-30 | The Feinstein Institute For Medical Research | Methods and systems for reducing inflammation by neuromodulation and administration of an anti-inflammatory drug |
| KR20110019781A (ko) | 2008-06-20 | 2011-02-28 | 아스트라제네카 아베 | 디벤조티아제핀 유도체 및 그의 용도 |
| ES2452484T3 (es) | 2008-11-18 | 2014-04-01 | Setpoint Medical Corporation | Dispositivos para optimizar la colocación de electrodos para la estimulación antiinflamatoria |
| TW201031664A (en) | 2009-01-26 | 2010-09-01 | Targacept Inc | Preparation and therapeutic applications of (2S,3R)-N-2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)-3,5-difluorobenzamide |
| EP2391628A4 (en) * | 2009-01-28 | 2012-10-10 | Astrazeneca Ab | 2-AZA-BICYCLOÝ2.2.1¨HEPTANE COMPOUNDS AND USES THEREOF |
| US8996116B2 (en) | 2009-10-30 | 2015-03-31 | Setpoint Medical Corporation | Modulation of the cholinergic anti-inflammatory pathway to treat pain or addiction |
| US9211410B2 (en) | 2009-05-01 | 2015-12-15 | Setpoint Medical Corporation | Extremely low duty-cycle activation of the cholinergic anti-inflammatory pathway to treat chronic inflammation |
| CN102573986B (zh) | 2009-06-09 | 2016-01-20 | 赛博恩特医疗器械公司 | 用于无导线刺激器的具有袋部的神经封套 |
| FR2948368B1 (fr) * | 2009-07-21 | 2011-07-22 | Servier Lab | Nouveaux composes piperidiniques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| US9833621B2 (en) | 2011-09-23 | 2017-12-05 | Setpoint Medical Corporation | Modulation of sirtuins by vagus nerve stimulation |
| WO2014169145A1 (en) | 2013-04-10 | 2014-10-16 | Setpoint Medical Corporation | Closed-loop vagus nerve stimulation |
| CN102821814B (zh) | 2009-12-23 | 2015-07-15 | 赛博恩特医疗器械公司 | 用于治疗慢性炎症的神经刺激设备和系统 |
| KR20180101641A (ko) | 2010-05-17 | 2018-09-12 | 포럼 파마슈티칼즈 인크. | (R)-7-클로로-N-(퀴누클리딘-3-일)벤조[b]티오펜-2-카르복사미드 히드로클로리드 모노히드레이트의 결정질 형태 |
| CA2808630A1 (en) | 2010-08-19 | 2012-02-23 | Buck Institute For Age Research | Methods of treating mild cognitive impairment (mci) and related disorders |
| US12172017B2 (en) | 2011-05-09 | 2024-12-24 | Setpoint Medical Corporation | Vagus nerve stimulation to treat neurodegenerative disorders |
| WO2012154865A2 (en) | 2011-05-09 | 2012-11-15 | Setpoint Medical Corporation | Single-pulse activation of the cholinergic anti-inflammatory pathway to treat chronic inflammation |
| GB201111704D0 (en) | 2011-07-07 | 2011-08-24 | Takeda Pharmaceutical | Novel compounds |
| GB201111705D0 (en) | 2011-07-07 | 2011-08-24 | Takeda Pharmaceutical | Compounds and their use |
| JO3115B1 (ar) | 2011-08-22 | 2017-09-20 | Takeda Pharmaceuticals Co | مركبات بيريدازينون واستخدامها كمثبطات daao |
| US9572983B2 (en) | 2012-03-26 | 2017-02-21 | Setpoint Medical Corporation | Devices and methods for modulation of bone erosion |
| EP3461481A1 (en) | 2012-05-08 | 2019-04-03 | Forum Pharmaceuticals Inc. | Methods of maintaining, treating or improving cognitive function |
| GB201209587D0 (en) | 2012-05-30 | 2012-07-11 | Takeda Pharmaceutical | Therapeutic compounds |
| JOP20130273B1 (ar) | 2012-09-11 | 2021-08-17 | Genzyme Corp | مثبطات انزيم (سينثاز) غلوكوسيل سيراميد |
| ES2694299T3 (es) | 2013-02-07 | 2018-12-19 | Heptares Therapeutics Limited | Carboxilatos de piperidin-1-ilo y azepin-1-ilo como agonistas del receptor muscarínico M4 |
| CN108658970A (zh) | 2013-03-15 | 2018-10-16 | 建新公司 | 制备葡萄糖基神经酰胺合酶抑制剂的方法 |
| AU2014282977B2 (en) | 2013-06-21 | 2018-06-14 | Takeda Pharmaceutical Company Limited | 1-sulfonyl piperidine derivatives as modulators of prokineticin receptors |
| GB201314286D0 (en) | 2013-08-08 | 2013-09-25 | Takeda Pharmaceutical | Therapeutic Compounds |
| GB201318222D0 (en) | 2013-10-15 | 2013-11-27 | Takeda Pharmaceutical | Novel compounds |
| GB201320905D0 (en) | 2013-11-27 | 2014-01-08 | Takeda Pharmaceutical | Therapeutic compounds |
| TW201613864A (en) | 2014-02-20 | 2016-04-16 | Takeda Pharmaceutical | Novel compounds |
| EP3166940A4 (en) | 2014-07-11 | 2018-04-25 | Alpharmagen, LLC | Quinuclidine compounds for modulating alpha7 -nicotinic acetylcholine receptor activity |
| US11311725B2 (en) | 2014-10-24 | 2022-04-26 | Setpoint Medical Corporation | Systems and methods for stimulating and/or monitoring loci in the brain to treat inflammation and to enhance vagus nerve stimulation |
| WO2016126807A1 (en) | 2015-02-03 | 2016-08-11 | Setpoint Medical Corporation | Apparatus and method for reminding, prompting, or alerting a patient with an implanted stimulator |
| US9724340B2 (en) | 2015-07-31 | 2017-08-08 | Attenua, Inc. | Antitussive compositions and methods |
| US10596367B2 (en) | 2016-01-13 | 2020-03-24 | Setpoint Medical Corporation | Systems and methods for establishing a nerve block |
| WO2017127758A1 (en) | 2016-01-20 | 2017-07-27 | Setpoint Medical Corporation | Implantable microstimulators and inductive charging systems |
| US11471681B2 (en) | 2016-01-20 | 2022-10-18 | Setpoint Medical Corporation | Batteryless implantable microstimulators |
| CN108882885A (zh) | 2016-01-20 | 2018-11-23 | 赛博恩特医疗器械公司 | 迷走神经刺激的控制 |
| US10583304B2 (en) | 2016-01-25 | 2020-03-10 | Setpoint Medical Corporation | Implantable neurostimulator having power control and thermal regulation and methods of use |
| GB201616839D0 (en) | 2016-10-04 | 2016-11-16 | Takeda Pharmaceutical Company Limited | Therapeutic compounds |
| GB201619514D0 (en) | 2016-11-18 | 2017-01-04 | Takeda Pharmaceuticals Co | Novel compounds |
| DE102017210141A1 (de) | 2017-06-16 | 2018-12-20 | Henkel Ag & Co. Kgaa | Portion zur Bereitstellung tensidhaltiger Flotten |
| WO2019036470A1 (en) | 2017-08-14 | 2019-02-21 | Setpoint Medical Corporation | TESTING TEST FOR STIMULATION OF NERVE WAVE |
| US11660443B2 (en) | 2018-04-20 | 2023-05-30 | The Feinstein Institutes For Medical Research | Methods and apparatuses for reducing bleeding via electrical trigeminal nerve stimulation |
| US11260229B2 (en) | 2018-09-25 | 2022-03-01 | The Feinstein Institutes For Medical Research | Methods and apparatuses for reducing bleeding via coordinated trigeminal and vagal nerve stimulation |
| PT3920912T (pt) | 2019-02-04 | 2025-09-09 | Genzyme Corp | Tratamento de ciliopatias usando inibidores da glucosilceramida sintase (gcs) |
| US12343535B2 (en) | 2019-04-12 | 2025-07-01 | Setpoint Medical Corporation | Vagus nerve stimulation to treat neurodegenerative disorders |
| KR20210059633A (ko) * | 2019-11-15 | 2021-05-25 | 주식회사유한양행 | 신규의 1,2,3,4-테트라하이드로나프탈렌 모이어티를 갖는 유도체 또는 이의 약학적으로 허용가능한 염, 이의 제조방법, 및 이를 포함하는 약학 조성물 |
| WO2021096238A1 (en) * | 2019-11-15 | 2021-05-20 | Yuhan Corporation | Novel derivatives having 2,3-dihydro-1h-indene or 2,3-dihydrobenzofuran moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same |
| JP2023512447A (ja) | 2020-01-13 | 2023-03-27 | ザ ファインスタイン インスティチューツ フォー メディカル リサーチ | 脾臓への高密度集束超音波刺激による出血及び出血性疾患の治療 |
| EP4100009A1 (en) | 2020-02-03 | 2022-12-14 | Genzyme Corporation | Methods for treating neurological symptoms associated with lysosomal storage diseases |
| JP2021138648A (ja) | 2020-03-04 | 2021-09-16 | 武田薬品工業株式会社 | 経口固形製剤 |
| US11938324B2 (en) | 2020-05-21 | 2024-03-26 | The Feinstein Institutes For Medical Research | Systems and methods for vagus nerve stimulation |
| CA3186766A1 (en) | 2020-07-24 | 2022-01-27 | Danielle Combessis | Pharmaceutical compositions comprising venglustat |
| WO2022240116A1 (en) * | 2021-05-11 | 2022-11-17 | Yuhan Corporation | Novel compounds having inhibitory activity against glucosylceramide synthase or pharmaceutically acceptable salt thereof, processes for preparing the same, and pharmaceutical compositions comprising the same |
| US12444497B2 (en) | 2021-05-17 | 2025-10-14 | Setpoint Medical Corporation | Neurostimulation parameter authentication and expiration system for neurostimulation |
| EP4608828A1 (en) * | 2022-10-24 | 2025-09-03 | Yuhan Corporation | Improved processes for preparing dimethyl-2,3-dihydro-1h-indene derivatives |
| JP2025537478A (ja) * | 2022-10-24 | 2025-11-18 | ユーハン・コーポレイション | ジメチル－２，３－ジヒドロ－１ｈ－インデン誘導体の新規塩およびその製造方法 |
| WO2025159544A1 (en) * | 2024-01-26 | 2025-07-31 | Yuhan Corporation | Pharmaceutical composition for preventing or treating gaucher disease |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SU482990A1 (ru) * | 1973-09-03 | 1978-04-15 | Предприятие П/Я Г-4059 | Способ получени 1,4-диазабицикло(2,2,2)-октана |
| DE8817121U1 (de) * | 1988-11-22 | 1993-02-04 | Boehringer Ingelheim Kg, 55218 Ingelheim | Neue Quinuclidine |
| JP3169188B2 (ja) * | 1991-01-31 | 2001-05-21 | 杏林製薬株式会社 | カルバミン酸誘導体及びその製造方法 |
| US5530018A (en) * | 1994-02-04 | 1996-06-25 | G. D. Searle & Co. | Meso-azanoradamantanes |
| US5468875A (en) * | 1994-12-22 | 1995-11-21 | American Home Products Corporation | 1-azabicycloheptane derivatives |
-
1996
- 1996-02-23 SE SE9600683A patent/SE9600683D0/xx unknown
-
1997
- 1997-02-10 ZA ZA9701082A patent/ZA971082B/xx unknown
- 1997-02-17 AR ARP970100618A patent/AR005876A1/es not_active Application Discontinuation
- 1997-02-20 ID IDP970487A patent/ID15969A/id unknown
- 1997-02-21 KR KR1019980706579A patent/KR19990087184A/ko not_active Withdrawn
- 1997-02-21 CZ CZ19982659A patent/CZ289110B6/cs not_active IP Right Cessation
- 1997-02-21 DE DE69713295T patent/DE69713295T2/de not_active Expired - Fee Related
- 1997-02-21 BR BR9707616A patent/BR9707616A/pt unknown
- 1997-02-21 CA CA002246051A patent/CA2246051A1/en not_active Abandoned
- 1997-02-21 TR TR1998/01642T patent/TR199801642T2/xx unknown
- 1997-02-21 NZ NZ331145A patent/NZ331145A/en unknown
- 1997-02-21 HU HU9901273A patent/HUP9901273A3/hu unknown
- 1997-02-21 PL PL97328614A patent/PL328614A1/xx unknown
- 1997-02-21 EP EP97905544A patent/EP0885221B1/en not_active Expired - Lifetime
- 1997-02-21 SK SK1027-98A patent/SK102798A3/sk unknown
- 1997-02-21 CN CN97192461A patent/CN1063749C/zh not_active Expired - Fee Related
- 1997-02-21 IL IL12562097A patent/IL125620A/en not_active IP Right Cessation
- 1997-02-21 US US08/836,143 patent/US5998429A/en not_active Expired - Fee Related
- 1997-02-21 RU RU98117804A patent/RU2172739C2/ru active
- 1997-02-21 AT AT97905544T patent/ATE219081T1/de active
- 1997-02-21 JP JP9530075A patent/JP2000505452A/ja not_active Ceased
- 1997-02-21 WO PCT/SE1997/000294 patent/WO1997030998A1/en not_active Ceased
- 1997-02-21 AU AU22387/97A patent/AU706944B2/en not_active Ceased
- 1997-02-21 EE EE9800250A patent/EE9800250A/xx unknown
-
1998
- 1998-08-13 NO NO983711A patent/NO983711L/no not_active Application Discontinuation
- 1998-08-20 IS IS4830A patent/IS4830A/is unknown
-
1999
- 1999-03-26 US US09/276,689 patent/US6054464A/en not_active Expired - Fee Related
-
2000
- 2000-07-30 IL IL13758500A patent/IL137585A0/xx unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69713295T2 (de) | Azabicyclishe carbaniumsaureester zur therapeutsichen verwendung | |
| DE69516524T2 (de) | Therapeutisch verwendbare spiro-azabicyclische verbindungen | |
| DE60005054T2 (de) | Chinuclidin-acrylamide | |
| DE69208877T2 (de) | Chinuclidinderivate | |
| DE60020994T2 (de) | Neue verwendung sowie neue n-azabicycloamid-verbindungen | |
| EP1448530B1 (de) | Heteroarylcarbonsäureamide | |
| DE60208366T2 (de) | Substituierte azabicyclische einheiten zur krankheitsbehandlung (nikotinische acetylcholinrezeptor-antagonisten) | |
| DE60102581T2 (de) | Azabizyklische carbamate und ihre anwendung als antagonisten des alpha-7 nikotinischen acetylcholin rezeptors | |
| DE60100996T2 (de) | Biarylcarboxamide | |
| DE69232334T2 (de) | Substituierte 3-aminochinuclidine | |
| DE60311853T2 (de) | Neue 1,4-diazabicycloalkanderivate, deren herstellung und verwendung | |
| DE60309740T2 (de) | 1,4-dizabicyclo(3,2,2)nonane derivative, verfahren zu ihrer herstellung und therapeutical verwendung | |
| EP1458716B1 (de) | Bicyclische n-arylamide | |
| DE69329018T2 (de) | Heterocyclische verbindungen, deren herstellung und verwendung | |
| DE3877470T2 (de) | Oxazole und thiazole zur behandlung seniler demenz. | |
| EP1487835A1 (de) | Essig- und propionsäureamide | |
| DE69205312T2 (de) | Substituierte Imidazol-2-one Derivate und Verfahren zu deren Herstellung. | |
| EP1651645B1 (de) | N-biarylamide | |
| DE69810107T2 (de) | Azacyclooktan- und heptan-derivate, ihre herstellung und ihre therapeutische verwendung | |
| DE10162442A1 (de) | Monocyclische N-Aryl-amide | |
| DE69026936T2 (de) | 5-aminocarbonyl-5h-dibenzo-a,d]cyclohepten-5,10-imine zur behandlung von epilepsie und kokainsucht | |
| DE602004006767T2 (de) | Nichtamidnonane | |
| EP0813532A1 (en) | PREPARATION OF CHIRAL 5-AMINOCARBONYL-5H-DIBENZO- a,d]CYCLOHEPTEN-5,10-IMINES BY OPTICAL RESOLUTION | |
| JPH1081684A (ja) | 置換３−アミノキヌクリジン薬剤組成物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8339 | Ceased/non-payment of the annual fee |