AU783602B2 - Positive modulators of nicotinic receptor agonists - Google Patents
Positive modulators of nicotinic receptor agonists Download PDFInfo
- Publication number
- AU783602B2 AU783602B2 AU14263/01A AU1426301A AU783602B2 AU 783602 B2 AU783602 B2 AU 783602B2 AU 14263/01 A AU14263/01 A AU 14263/01A AU 1426301 A AU1426301 A AU 1426301A AU 783602 B2 AU783602 B2 AU 783602B2
- Authority
- AU
- Australia
- Prior art keywords
- methyl
- indole
- disease
- hydroxy
- formula
- 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.)
- Ceased
Links
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 title claims description 23
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 title claims description 23
- 229940044601 receptor agonist Drugs 0.000 title description 16
- 239000000018 receptor agonist Substances 0.000 title description 16
- 150000001875 compounds Chemical class 0.000 claims description 163
- 238000000034 method Methods 0.000 claims description 64
- 229940123925 Nicotinic receptor agonist Drugs 0.000 claims description 28
- 239000000181 nicotinic agonist Substances 0.000 claims description 28
- 239000001257 hydrogen Substances 0.000 claims description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 26
- 238000011282 treatment Methods 0.000 claims description 26
- 150000002431 hydrogen Chemical class 0.000 claims description 19
- 208000035475 disorder Diseases 0.000 claims description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims description 18
- 230000006735 deficit Effects 0.000 claims description 17
- 239000000556 agonist Substances 0.000 claims description 15
- 238000011321 prophylaxis Methods 0.000 claims description 15
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 12
- 208000024827 Alzheimer disease Diseases 0.000 claims description 12
- 229960002715 nicotine Drugs 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 201000000980 schizophrenia Diseases 0.000 claims description 9
- 208000019901 Anxiety disease Diseases 0.000 claims description 8
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 8
- 208000018737 Parkinson disease Diseases 0.000 claims description 8
- 208000000323 Tourette Syndrome Diseases 0.000 claims description 8
- 208000016620 Tourette disease Diseases 0.000 claims description 8
- 230000004913 activation Effects 0.000 claims description 8
- 230000036506 anxiety Effects 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 208000000044 Amnesia Diseases 0.000 claims description 7
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 7
- 208000020925 Bipolar disease Diseases 0.000 claims description 7
- 208000023105 Huntington disease Diseases 0.000 claims description 7
- 208000009829 Lewy Body Disease Diseases 0.000 claims description 7
- 201000002832 Lewy body dementia Diseases 0.000 claims description 7
- 206010026749 Mania Diseases 0.000 claims description 7
- 208000026139 Memory disease Diseases 0.000 claims description 7
- 206010057852 Nicotine dependence Diseases 0.000 claims description 7
- 208000025569 Tobacco Use disease Diseases 0.000 claims description 7
- 230000003935 attention Effects 0.000 claims description 7
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 208000028683 bipolar I disease Diseases 0.000 claims description 7
- 230000007278 cognition impairment Effects 0.000 claims description 7
- 230000006984 memory degeneration Effects 0.000 claims description 7
- 208000023060 memory loss Diseases 0.000 claims description 7
- 230000002829 reductive effect Effects 0.000 claims description 7
- QTAABPDKPSKCNJ-UHFFFAOYSA-N 4-hydroxy-1-methylindole-2-carboxamide Chemical compound C1=CC=C2N(C)C(C(N)=O)=CC2=C1O QTAABPDKPSKCNJ-UHFFFAOYSA-N 0.000 claims description 6
- 208000019888 Circadian rhythm sleep disease Diseases 0.000 claims description 6
- 208000001456 Jet Lag Syndrome Diseases 0.000 claims description 6
- 208000033915 jet lag type circadian rhythm sleep disease Diseases 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 230000005540 biological transmission Effects 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- NCFRPTLPGWKEIX-UHFFFAOYSA-N ethyl 4-hydroxy-1-methylindole-2-carboxylate Chemical compound C1=CC=C2N(C)C(C(=O)OCC)=CC2=C1O NCFRPTLPGWKEIX-UHFFFAOYSA-N 0.000 claims description 2
- GDXAEGSNSMJISF-UHFFFAOYSA-N n-[[4-(dimethylamino)phenyl]methyl]-4-hydroxy-1-methylindole-2-carboxamide Chemical compound C1=CC(N(C)C)=CC=C1CNC(=O)C1=CC2=C(O)C=CC=C2N1C GDXAEGSNSMJISF-UHFFFAOYSA-N 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 206010009900 Colitis ulcerative Diseases 0.000 claims 6
- 208000002193 Pain Diseases 0.000 claims 6
- 201000006704 Ulcerative Colitis Diseases 0.000 claims 6
- 230000001713 cholinergic effect Effects 0.000 claims 6
- 208000015122 neurodegenerative disease Diseases 0.000 claims 6
- 210000000225 synapse Anatomy 0.000 claims 6
- 208000028017 Psychotic disease Diseases 0.000 claims 3
- 230000009286 beneficial effect Effects 0.000 claims 3
- 230000000391 smoking effect Effects 0.000 claims 3
- UWEAINNLPOKQDF-UHFFFAOYSA-N n-(2-fluoroethyl)-4-hydroxy-1-methylindole-2-carboxamide Chemical compound C1=CC=C2N(C)C(C(=O)NCCF)=CC2=C1O UWEAINNLPOKQDF-UHFFFAOYSA-N 0.000 claims 1
- DISOOVOIBKFPCC-UHFFFAOYSA-N n-[(4-chlorophenyl)methyl]-4-hydroxy-1-methylindole-2-carboxamide Chemical compound C=1C2=C(O)C=CC=C2N(C)C=1C(=O)NCC1=CC=C(Cl)C=C1 DISOOVOIBKFPCC-UHFFFAOYSA-N 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 38
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 31
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 239000002904 solvent Substances 0.000 description 29
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- 230000000694 effects Effects 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 19
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 239000002585 base Substances 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- 102000005962 receptors Human genes 0.000 description 12
- 108020003175 receptors Proteins 0.000 description 12
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 11
- 229960004373 acetylcholine Drugs 0.000 description 11
- -1 i-propenyl Chemical group 0.000 description 11
- 239000000203 mixture Substances 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- 210000000287 oocyte Anatomy 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- 239000011575 calcium Substances 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 230000004907 flux Effects 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- KHMVUGLKZABSPC-UHFFFAOYSA-N 1-methyl-4-phenylmethoxyindole-2-carboxylic acid Chemical compound C1=CC=C2N(C)C(C(O)=O)=CC2=C1OCC1=CC=CC=C1 KHMVUGLKZABSPC-UHFFFAOYSA-N 0.000 description 5
- 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 description 5
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 241000269370 Xenopus <genus> Species 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 239000003638 chemical reducing agent Substances 0.000 description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- 229910004373 HOAc Inorganic materials 0.000 description 3
- 239000012981 Hank's balanced salt solution Substances 0.000 description 3
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 239000012317 TBTU Substances 0.000 description 3
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 3
- 230000006978 adaptation Effects 0.000 description 3
- HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Inorganic materials [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 description 3
- 238000004296 chiral HPLC Methods 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 238000000586 desensitisation Methods 0.000 description 3
- WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 3
- WHQLQYRFIHPMNA-UHFFFAOYSA-N ethyl acetate;oxolane Chemical compound C1CCOC1.CCOC(C)=O WHQLQYRFIHPMNA-UHFFFAOYSA-N 0.000 description 3
- 238000007429 general method Methods 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 150000002902 organometallic compounds Chemical class 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- VZFHZIGTMHNFAC-UHFFFAOYSA-N (1-fluoro-3-phenylpropan-2-yl) methanesulfonate Chemical compound CS(=O)(=O)OC(CF)CC1=CC=CC=C1 VZFHZIGTMHNFAC-UHFFFAOYSA-N 0.000 description 2
- CJFDLCLVRZUIKO-UHFFFAOYSA-N (2-azido-3-fluoropropyl)benzene Chemical compound [N-]=[N+]=NC(CF)CC1=CC=CC=C1 CJFDLCLVRZUIKO-UHFFFAOYSA-N 0.000 description 2
- KZJGAIPOKXGDIA-SECBINFHSA-N (2r)-2-fluoro-3-phenylpropan-1-amine Chemical compound NC[C@H](F)CC1=CC=CC=C1 KZJGAIPOKXGDIA-SECBINFHSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- YPWHLIAQBWWRBW-UHFFFAOYSA-N 3-hydroxy-1-methylindole-2-carboxylic acid Chemical compound C1=CC=C2N(C)C(C(O)=O)=C(O)C2=C1 YPWHLIAQBWWRBW-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 108091006146 Channels Proteins 0.000 description 2
- 102000009660 Cholinergic Receptors Human genes 0.000 description 2
- 108010009685 Cholinergic Receptors Proteins 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 101000939500 Homo sapiens UBX domain-containing protein 11 Proteins 0.000 description 2
- 102000004310 Ion Channels Human genes 0.000 description 2
- 108090000862 Ion Channels Proteins 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
- 102000004086 Ligand-Gated Ion Channels Human genes 0.000 description 2
- 108090000543 Ligand-Gated Ion Channels Proteins 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 241001274216 Naso Species 0.000 description 2
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 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
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 2
- 102100029645 UBX domain-containing protein 11 Human genes 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 230000009460 calcium influx Effects 0.000 description 2
- 150000001718 carbodiimides Chemical class 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 150000001793 charged compounds Chemical class 0.000 description 2
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
- 229960001231 choline Drugs 0.000 description 2
- 230000001149 cognitive effect Effects 0.000 description 2
- UVJHQYIOXKWHFD-UHFFFAOYSA-N cyclohexa-1,4-diene Chemical compound C1C=CCC=C1 UVJHQYIOXKWHFD-UHFFFAOYSA-N 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 210000001320 hippocampus Anatomy 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 231100001231 less toxic Toxicity 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- PEXYWNARVQJCTP-VIFPVBQESA-N (2s)-1-azido-3-phenylpropan-2-amine Chemical compound [N-]=[N+]=NC[C@@H](N)CC1=CC=CC=C1 PEXYWNARVQJCTP-VIFPVBQESA-N 0.000 description 1
- YMVFJGSXZNNUDW-UHFFFAOYSA-N (4-chlorophenyl)methanamine Chemical compound NCC1=CC=C(Cl)C=C1 YMVFJGSXZNNUDW-UHFFFAOYSA-N 0.000 description 1
- IJXJGQCXFSSHNL-QMMMGPOBSA-N (R)-(-)-2-Phenylglycinol Chemical compound OC[C@H](N)C1=CC=CC=C1 IJXJGQCXFSSHNL-QMMMGPOBSA-N 0.000 description 1
- 229930182840 (S)-nicotine Natural products 0.000 description 1
- 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 1
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
- 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
- JJVPFVRQYKYZJT-UHFFFAOYSA-N 1-methyl-4-phenylmethoxyindole-2-carbonyl chloride Chemical compound C1=CC=C2N(C)C(C(Cl)=O)=CC2=C1OCC1=CC=CC=C1 JJVPFVRQYKYZJT-UHFFFAOYSA-N 0.000 description 1
- ZWEQNVMYOUDKQT-UHFFFAOYSA-N 1-phenylbut-3-yn-1-amine Chemical compound C#CCC(N)C1=CC=CC=C1 ZWEQNVMYOUDKQT-UHFFFAOYSA-N 0.000 description 1
- LRXFKKPEBXIPMW-UHFFFAOYSA-N 2-(9h-fluoren-2-yl)propanoic acid Chemical compound C1=CC=C2C3=CC=C(C(C(O)=O)C)C=C3CC2=C1 LRXFKKPEBXIPMW-UHFFFAOYSA-N 0.000 description 1
- MFGOFGRYDNHJTA-UHFFFAOYSA-N 2-amino-1-(2-fluorophenyl)ethanol Chemical compound NCC(O)C1=CC=CC=C1F MFGOFGRYDNHJTA-UHFFFAOYSA-N 0.000 description 1
- ISURUORMAKCTFF-UHFFFAOYSA-N 2-benzyl-1-(4-methylphenyl)sulfonylaziridine Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1C(CC=2C=CC=CC=2)C1 ISURUORMAKCTFF-UHFFFAOYSA-N 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- FURHRJBOFNDYTG-UHFFFAOYSA-N 2-fluoroethanamine Chemical compound NCCF FURHRJBOFNDYTG-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- QSNSCYSYFYORTR-UHFFFAOYSA-N 4-chloroaniline Chemical compound NC1=CC=C(Cl)C=C1 QSNSCYSYFYORTR-UHFFFAOYSA-N 0.000 description 1
- XMXWFSWWQPUYDJ-UHFFFAOYSA-N 4-hydroxy-1-methyl-n-(3-phenylpropyl)indole-2-carboxamide Chemical compound C=1C2=C(O)C=CC=C2N(C)C=1C(=O)NCCCC1=CC=CC=C1 XMXWFSWWQPUYDJ-UHFFFAOYSA-N 0.000 description 1
- VNUZXARZRWELJO-UHFFFAOYSA-N 4-hydroxy-1-methyl-n-(4-phenylbutyl)indole-2-carboxamide Chemical compound C=1C2=C(O)C=CC=C2N(C)C=1C(=O)NCCCCC1=CC=CC=C1 VNUZXARZRWELJO-UHFFFAOYSA-N 0.000 description 1
- FTFBINRINIORBJ-UHFFFAOYSA-N 4-hydroxy-1-methyl-n-phenylindole-2-carboxamide Chemical compound C=1C2=C(O)C=CC=C2N(C)C=1C(=O)NC1=CC=CC=C1 FTFBINRINIORBJ-UHFFFAOYSA-N 0.000 description 1
- CKZLTECAOSGTBC-UHFFFAOYSA-N 4-hydroxy-1-methylindole-2-carboxylic acid Chemical compound C1=CC=C2N(C)C(C(O)=O)=CC2=C1O CKZLTECAOSGTBC-UHFFFAOYSA-N 0.000 description 1
- 125000002373 5 membered heterocyclic group Chemical group 0.000 description 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
- 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 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
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 101150047265 COR2 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- OZLGRUXZXMRXGP-UHFFFAOYSA-N Fluo-3 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C2=C3C=C(Cl)C(=O)C=C3OC3=CC(O)=C(Cl)C=C32)N(CC(O)=O)CC(O)=O)=C1 OZLGRUXZXMRXGP-UHFFFAOYSA-N 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 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
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- UQOFGTXDASPNLL-XHNCKOQMSA-N Muscarine Chemical compound C[C@@H]1O[C@H](C[N+](C)(C)C)C[C@H]1O UQOFGTXDASPNLL-XHNCKOQMSA-N 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 1
- 101100168115 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) con-6 gene Proteins 0.000 description 1
- 241000208125 Nicotiana Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- GEYBMYRBIABFTA-VIFPVBQESA-N O-methyl-L-tyrosine Chemical compound COC1=CC=C(C[C@H](N)C(O)=O)C=C1 GEYBMYRBIABFTA-VIFPVBQESA-N 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 101100467189 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) QCR2 gene Proteins 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 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
- 102000004338 Transferrin Human genes 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- 241000269368 Xenopus laevis Species 0.000 description 1
- 241000012481 Xiha Species 0.000 description 1
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 230000003281 allosteric effect Effects 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 238000003287 bathing Methods 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000000451 chemical ionisation Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000006949 cholinergic function Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 238000003821 enantio-separation Methods 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- ZEJBFCQPRRMXMQ-UHFFFAOYSA-N ethyl 1-methyl-4-phenylmethoxyindole-2-carboxylate Chemical compound C1=CC=C2N(C)C(C(=O)OCC)=CC2=C1OCC1=CC=CC=C1 ZEJBFCQPRRMXMQ-UHFFFAOYSA-N 0.000 description 1
- HIQPISGKBJHKIN-UHFFFAOYSA-N ethyl 4-phenylmethoxy-1h-indole-2-carboxylate Chemical compound C1=CC=C2NC(C(=O)OCC)=CC2=C1OCC1=CC=CC=C1 HIQPISGKBJHKIN-UHFFFAOYSA-N 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 210000003754 fetus Anatomy 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 229960002743 glutamine Drugs 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- HCUARRIEZVDMPT-UHFFFAOYSA-N indolyl-2-carboxylic acid Natural products C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 238000000752 ionisation method Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 210000002418 meninge Anatomy 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000000897 modulatory effect Effects 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 230000003551 muscarinic effect Effects 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- LZBFIJHOKKJZKY-UHFFFAOYSA-N n-(1-fluoro-3-phenylpropan-2-yl)-1-methyl-4-phenylmethoxyindole-2-carboxamide Chemical compound C1=CC=C2N(C)C(C(=O)NC(CF)CC=3C=CC=CC=3)=CC2=C1OCC1=CC=CC=C1 LZBFIJHOKKJZKY-UHFFFAOYSA-N 0.000 description 1
- MPKQMEXBCWRJSI-UHFFFAOYSA-N n-(4-chlorophenyl)-4-hydroxy-1-methylindole-2-carboxamide Chemical compound C=1C2=C(O)C=CC=C2N(C)C=1C(=O)NC1=CC=C(Cl)C=C1 MPKQMEXBCWRJSI-UHFFFAOYSA-N 0.000 description 1
- RVBWYMDPXVGCAH-OAHLLOKOSA-N n-[(2r)-2-fluoro-3-phenylpropyl]-4-methylbenzenesulfonamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC[C@H](F)CC1=CC=CC=C1 RVBWYMDPXVGCAH-OAHLLOKOSA-N 0.000 description 1
- NHZLWLAHJVXVQW-UHFFFAOYSA-N n-benzyl-4-hydroxy-1-methylindole-2-carboxamide Chemical compound C=1C2=C(O)C=CC=C2N(C)C=1C(=O)NCC1=CC=CC=C1 NHZLWLAHJVXVQW-UHFFFAOYSA-N 0.000 description 1
- 125000004370 n-butenyl group Chemical group [H]\C([H])=C(/[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000004112 neuroprotection Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 230000000422 nocturnal effect Effects 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
- 239000012044 organic layer Substances 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229940117803 phenethylamine Drugs 0.000 description 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 229960002816 potassium chloride Drugs 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- GRJJQCWNZGRKAU-UHFFFAOYSA-N pyridin-1-ium;fluoride Chemical compound F.C1=CC=NC=C1 GRJJQCWNZGRKAU-UHFFFAOYSA-N 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 238000006894 reductive elimination reaction Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 230000036390 resting membrane potential Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000000779 smoke Substances 0.000 description 1
- 230000005586 smoking cessation Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000012321 sodium triacetoxyborohydride 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
- 239000007858 starting material Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 235000001508 sulfur Nutrition 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 230000002123 temporal effect Effects 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
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 229940072040 tricaine Drugs 0.000 description 1
- FQZJYWMRQDKBQN-UHFFFAOYSA-N tricaine methanesulfonate Chemical compound CS([O-])(=O)=O.CCOC(=O)C1=CC=CC([NH3+])=C1 FQZJYWMRQDKBQN-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 230000036967 uncompetitive effect Effects 0.000 description 1
- 125000005500 uronium group Chemical group 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- General Chemical & Material Sciences (AREA)
- Psychiatry (AREA)
- Addiction (AREA)
- Psychology (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9903998 | 1999-11-03 | ||
| SE9903998A SE9903998D0 (sv) | 1999-11-03 | 1999-11-03 | New compounds |
| PCT/SE2000/002147 WO2001032622A1 (en) | 1999-11-03 | 2000-11-01 | Positive modulators of nicotinic receptor agonists |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU1426301A AU1426301A (en) | 2001-05-14 |
| AU783602B2 true AU783602B2 (en) | 2005-11-10 |
Family
ID=20417608
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU14263/01A Ceased AU783602B2 (en) | 1999-11-03 | 2000-11-01 | Positive modulators of nicotinic receptor agonists |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US7064143B1 (enExample) |
| EP (1) | EP1230218A1 (enExample) |
| JP (1) | JP2003513073A (enExample) |
| KR (1) | KR20020063175A (enExample) |
| CN (1) | CN1216864C (enExample) |
| AU (1) | AU783602B2 (enExample) |
| BR (1) | BR0015193A (enExample) |
| CA (1) | CA2387741A1 (enExample) |
| CO (1) | CO5280079A1 (enExample) |
| IL (1) | IL149096A0 (enExample) |
| MX (1) | MXPA02004240A (enExample) |
| NO (1) | NO323077B1 (enExample) |
| NZ (1) | NZ518449A (enExample) |
| SE (1) | SE9903998D0 (enExample) |
| WO (1) | WO2001032622A1 (enExample) |
| ZA (1) | ZA200203181B (enExample) |
Families Citing this family (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003039540A2 (en) * | 2001-11-09 | 2003-05-15 | Sepracor Inc. | D-amino acid oxidase inhibitors for learning and memory |
| DE10164139A1 (de) | 2001-12-27 | 2003-07-10 | Bayer Ag | 2-Heteroarylcarbonsäureamide |
| GB0205166D0 (en) | 2002-03-06 | 2002-04-17 | Astrazeneca Ab | Chemical compounds |
| GB0205176D0 (en) | 2002-03-06 | 2002-04-17 | Astrazeneca Ab | Chemical compounds |
| GB0205170D0 (en) | 2002-03-06 | 2002-04-17 | Astrazeneca Ab | Chemical compounds |
| GB0205175D0 (en) | 2002-03-06 | 2002-04-17 | Astrazeneca Ab | Chemical compounds |
| GB0205165D0 (en) | 2002-03-06 | 2002-04-17 | Astrazeneca Ab | Chemical compounds |
| GB0205162D0 (en) | 2002-03-06 | 2002-04-17 | Astrazeneca Ab | Chemical compounds |
| US7244745B2 (en) | 2002-08-30 | 2007-07-17 | Memory Pharmaceuticals Corp. | Heterocyclic compounds, methods for the preparation thereof, and uses thereof |
| ES2405594T3 (es) | 2002-09-25 | 2013-05-31 | Memory Pharmaceuticals Corporation | Idazoles, benzotiazoles y benzisotiazoles, y preparación y usos de los mismos |
| GB0222909D0 (en) | 2002-10-03 | 2002-11-13 | Astrazeneca Ab | Novel process and intermediates |
| GB0222912D0 (en) | 2002-10-03 | 2002-11-13 | Astrazeneca Ab | Novel process and intermediates |
| US7405210B2 (en) | 2003-05-21 | 2008-07-29 | Osi Pharmaceuticals, Inc. | Pyrrolopyridine-2-carboxylic acid amide inhibitors of glycogen phosphorylase |
| US20070191815A1 (en) | 2004-09-13 | 2007-08-16 | Chrono Therapeutics, Inc. | Biosynchronous transdermal drug delivery |
| WO2005066135A2 (en) | 2003-12-29 | 2005-07-21 | Sepracor Inc. | Pyrrole and pyrazole daao inhibitors |
| ES2353309T3 (es) | 2004-03-08 | 2011-03-01 | Prosidion Ltd. | Hidrazidas del ácido pirrolopiridin-2-carboxílico como inhibidores de glucógeno fosforilasa. |
| BRPI0508771A (pt) | 2004-03-25 | 2007-08-14 | Memory Pharm Corp | indazóis, benzotiazóis, benzoisotiazóis, benzisoxazóis, e a preparação e usos dos mesmos |
| ATE462692T1 (de) | 2004-06-01 | 2010-04-15 | Hoffmann La Roche | 3-amino-1-arylpropyl-indole als monoamin- wiederaufnahmehemmer |
| US8252321B2 (en) | 2004-09-13 | 2012-08-28 | Chrono Therapeutics, Inc. | Biosynchronous transdermal drug delivery for longevity, anti-aging, fatigue management, obesity, weight loss, weight management, delivery of nutraceuticals, and the treatment of hyperglycemia, alzheimer's disease, sleep disorders, parkinson's disease, aids, epilepsy, attention deficit disorder, nicotine addiction, cancer, headache and pain control, asthma, angina, hypertension, depression, cold, flu and the like |
| WO2006053274A2 (en) | 2004-11-15 | 2006-05-18 | Bristol-Myers Squibb Company | 2-amino-1-functionalized tetralin derivatives and related glycogen phosphorylase inhibitors |
| US7226942B2 (en) | 2004-11-15 | 2007-06-05 | Bristol-Myers Squibb Company | 2-amino-4-functionalized tetralin derivatives and related glycogen phosphorylase inhibitors |
| WO2006055435A1 (en) | 2004-11-15 | 2006-05-26 | Bristol-Myers Squibb Company | 2-aminonaphthalene derivatives and related glycogen phosphorylase inhibitors |
| US7365061B2 (en) | 2004-11-15 | 2008-04-29 | Bristol-Myers Squibb Company | 2-Amino-3-functionalized tetralin derivatives and related glycogen phosphorylase inhibitors |
| EP1819332B1 (en) | 2004-12-02 | 2009-03-11 | Prosidion Limited | Pyrrolopyridine-2-carboxylic acid amides |
| FR2888847B1 (fr) | 2005-07-22 | 2007-08-31 | Sanofi Aventis Sa | Derives de n-(heteriaryl)-1-heteorarylalkyl-1h-indole-2- carboxamides, leur preparation et application en therapeutique |
| WO2007062998A1 (en) | 2005-11-30 | 2007-06-07 | F. Hoffmann-La Roche Ag | 3-amino-2-arylpropyl azaindoles and uses thereof |
| CN101316818B (zh) | 2005-11-30 | 2011-08-31 | 弗·哈夫曼-拉罗切有限公司 | 3-氨基-1-芳基丙基吲哚类和氮杂取代的吲哚类 |
| ES2368416T3 (es) | 2005-11-30 | 2011-11-17 | F. Hoffmann-La Roche Ag | Procedimiento para la síntesis de 3-amino-1-arilpropil-indoles. |
| US7884124B2 (en) | 2006-06-30 | 2011-02-08 | Sepracor Inc. | Fluoro-substituted inhibitors of D-amino acid oxidase |
| WO2008083729A1 (en) * | 2007-01-09 | 2008-07-17 | Bayer Schering Pharma Aktiengesellschaft | Radiolabelling via fluorination of aziridines |
| EP1944288A1 (en) * | 2007-01-09 | 2008-07-16 | Bayer Schering Pharma Aktiengesellschaft | Radiolabelling via fluorination of aziridines |
| EP2322168A1 (en) * | 2007-04-02 | 2011-05-18 | Parkinson's Institute | Methods and Compositions for Reduction of Side Effects of Therapeutic Treatments |
| US8383657B2 (en) | 2007-12-21 | 2013-02-26 | Abbott Laboratories | Thiazolylidine urea and amide derivatives and methods of use thereof |
| CN103221411B (zh) | 2010-05-17 | 2016-05-11 | 富瑞姆制药公司 | (R)-7-氯-N-(奎宁环-3-基)苯并[b]噻吩-2-甲酰胺盐酸盐单水合物的晶型 |
| AR085509A1 (es) | 2011-03-09 | 2013-10-09 | Bayer Cropscience Ag | Indol- y bencimidazolcarboxamidas como insecticidas y acaricidas |
| CA2841785A1 (en) | 2011-07-06 | 2013-01-10 | The Parkinson's Institute | Compositions and methods for treatment of symptoms in parkinson's disease patients |
| CA2872005A1 (en) | 2012-05-08 | 2013-11-14 | Forum Pharmaceuticals, Inc. | Methods of maintaining, treating or improving cognitive function |
| JP2018511355A (ja) | 2015-01-28 | 2018-04-26 | クロノ セラピューティクス インコーポレイテッドＣｈｒｏｎｏ Ｔｈｅｒａｐｅｕｔｉｃｓ Ｉｎｃ． | 薬剤送達方法及びシステム |
| AU2016228779A1 (en) | 2015-03-12 | 2017-09-07 | Chrono Therapeutics Inc. | Craving input and support system |
| JP2020503950A (ja) | 2017-01-06 | 2020-02-06 | クロノ セラピューティクス インコーポレイテッドＣｈｒｏｎｏ Ｔｈｅｒａｐｅｕｔｉｃｓ Ｉｎｃ． | 経皮薬剤送達の装置及び方法 |
| JP7420797B2 (ja) | 2018-05-29 | 2024-01-23 | モーニングサイド ベンチャー インベストメンツ リミテッド | 薬剤送達の方法及びシステム |
| CA3119992A1 (en) | 2018-11-16 | 2020-05-22 | Morningside Venture Investments Limited | Thermally regulated transdermal drug delivery system |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1310235A (en) * | 1969-11-17 | 1973-03-14 | Ici Ltd | Heterocyclyloxymethyl-morpholine or piperazine-derivatives |
| EP0722941A2 (en) * | 1995-01-17 | 1996-07-24 | Eli Lilly And Company | Compounds having effects on serotonin-related systems |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4704390A (en) * | 1986-02-13 | 1987-11-03 | Warner-Lambert Company | Phenyl and heterocyclic tetrahydropyridyl alkoxy-benzheterocyclic compounds as antipsychotic agents |
| US5328922A (en) * | 1990-09-13 | 1994-07-12 | Beecham Group P.L.C. | Indole ureas as 5 ht receptor antagonist |
| AU671959B2 (en) | 1991-11-25 | 1996-09-19 | Pfizer Inc. | Indole derivatives |
| WO1993018026A1 (en) * | 1992-03-04 | 1993-09-16 | Beecham Group Plc | Indole ureas as 5-ht1c receptor antogonists |
| US5504101A (en) | 1994-05-06 | 1996-04-02 | Allelix Biopharmaceuticals, Inc. | 5-HT-1D receptor ligands |
| FR2722686B1 (fr) | 1994-07-22 | 1996-08-30 | Oreal | Set, procede, dispositif et composition de teinture des fibres keratiniques |
| SE9903997D0 (sv) * | 1999-11-03 | 1999-11-03 | Astra Ab | New compounds |
-
1999
- 1999-11-03 SE SE9903998A patent/SE9903998D0/xx unknown
-
2000
- 2000-11-01 BR BR0015193-9A patent/BR0015193A/pt not_active IP Right Cessation
- 2000-11-01 KR KR1020027005705A patent/KR20020063175A/ko not_active Ceased
- 2000-11-01 CA CA002387741A patent/CA2387741A1/en not_active Abandoned
- 2000-11-01 US US10/111,029 patent/US7064143B1/en not_active Expired - Fee Related
- 2000-11-01 MX MXPA02004240A patent/MXPA02004240A/es not_active Application Discontinuation
- 2000-11-01 AU AU14263/01A patent/AU783602B2/en not_active Ceased
- 2000-11-01 CN CN008154406A patent/CN1216864C/zh not_active Expired - Fee Related
- 2000-11-01 NZ NZ518449A patent/NZ518449A/en unknown
- 2000-11-01 IL IL14909600A patent/IL149096A0/xx unknown
- 2000-11-01 JP JP2001534774A patent/JP2003513073A/ja not_active Abandoned
- 2000-11-01 WO PCT/SE2000/002147 patent/WO2001032622A1/en not_active Ceased
- 2000-11-01 CO CO00083137A patent/CO5280079A1/es not_active Application Discontinuation
- 2000-11-01 EP EP00976499A patent/EP1230218A1/en not_active Withdrawn
-
2002
- 2002-04-22 ZA ZA200203181A patent/ZA200203181B/xx unknown
- 2002-05-02 NO NO20022105A patent/NO323077B1/no unknown
-
2005
- 2005-07-11 US US11/178,668 patent/US7402604B2/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1310235A (en) * | 1969-11-17 | 1973-03-14 | Ici Ltd | Heterocyclyloxymethyl-morpholine or piperazine-derivatives |
| EP0722941A2 (en) * | 1995-01-17 | 1996-07-24 | Eli Lilly And Company | Compounds having effects on serotonin-related systems |
Non-Patent Citations (1)
| Title |
|---|
| PHYTOCHEMISTRY, VOL. 11, 1972, PP 1623-1630 * |
Also Published As
| Publication number | Publication date |
|---|---|
| ZA200203181B (en) | 2003-07-22 |
| CA2387741A1 (en) | 2001-05-10 |
| US20050245595A1 (en) | 2005-11-03 |
| NO20022105L (no) | 2002-07-02 |
| CN1387513A (zh) | 2002-12-25 |
| AU1426301A (en) | 2001-05-14 |
| WO2001032622A1 (en) | 2001-05-10 |
| CN1216864C (zh) | 2005-08-31 |
| JP2003513073A (ja) | 2003-04-08 |
| US7402604B2 (en) | 2008-07-22 |
| SE9903998D0 (sv) | 1999-11-03 |
| US7064143B1 (en) | 2006-06-20 |
| KR20020063175A (ko) | 2002-08-01 |
| NZ518449A (en) | 2004-07-30 |
| BR0015193A (pt) | 2002-06-18 |
| EP1230218A1 (en) | 2002-08-14 |
| IL149096A0 (en) | 2002-11-10 |
| CO5280079A1 (es) | 2003-05-30 |
| NO323077B1 (no) | 2006-12-27 |
| NO20022105D0 (no) | 2002-05-02 |
| MXPA02004240A (es) | 2002-10-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU783602B2 (en) | Positive modulators of nicotinic receptor agonists | |
| AU783507B2 (en) | Positive modulators of nicotinic receptor agonists | |
| US5686482A (en) | N-(3-pyrrolidinyl) benzamide derivative | |
| PT1668985E (pt) | Ecteinascidinas e n-óxidos de ecteinascidinas com substituições nucleofílicas | |
| US20070179172A1 (en) | Positive modulators of nicotinic acetylcholine receptors | |
| US20080081833A1 (en) | Novel Pyrazole Derivatives And Their Use As Modulators Of Nicotinic Acetylcholine Receptors | |
| PT1717226E (pt) | Derivados de 5-amino-4-hidroxi-8-(1h-indol-5-il)-octan amida 2,7-substituída como inibidores da renina para o tratamento da hipertensão | |
| US20080051441A1 (en) | Aryl Sulphonamide Modulators | |
| MXPA06013629A (es) | Derivados de tetrahidroisoquinolilsulfonamidas, su preparacion y su utilizacion en terapeutica. | |
| EP1230217B1 (en) | Positive modulators of nicotinic receptor agonists | |
| Taborsky et al. | Synthesis and preliminary pharmacology of some 1-methylindoles | |
| HUP0103518A2 (hu) | Új 2,3,3a,4,9,9a-hexahidro-8-hidroxi-1H-benz[f]indol-származékok, eljárás előállításukra és alkalmazásuk gyógyszerkészítmények előállítására |