CA2146000A1 - Derives de substitution en 3,3 d'indolin-2-ones tri- et tetracycliques, utiles pour le traitement de troubles cognitifs - Google Patents

Derives de substitution en 3,3 d'indolin-2-ones tri- et tetracycliques, utiles pour le traitement de troubles cognitifs

Info

Publication number: CA2146000A1
Authority: CA; Canada
Prior art keywords: pyr; pyrim; group; carbons; compound
Prior art date: 1992-10-13
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.): Abandoned

Application number

CA002146000A

Other languages

English (en)

Inventor

Richard Alan Earl

Melvyn John Myers

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Bristol Myers Squibb Pharma Co

Original Assignee

Individual

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1992-10-13

Filing date

1993-10-12

Publication date

1994-04-28

1993-10-12 Application filed by Individual filed Critical Individual

1994-04-28 Publication of CA2146000A1 publication Critical patent/CA2146000A1/fr

Status Abandoned legal-status Critical Current

Links

238000011282 treatment Methods 0.000 title abstract description 15
208000010877 cognitive disease Diseases 0.000 title description 6
150000005623 oxindoles Chemical class 0.000 title description 5
150000001875 compounds Chemical class 0.000 claims abstract description 78
238000000034 method Methods 0.000 claims description 23
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 22
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
125000000217 alkyl group Chemical group 0.000 claims description 19
-1 4-pyrazolyl Chemical group 0.000 claims description 17
125000003118 aryl group Chemical group 0.000 claims description 16
241000124008 Mammalia Species 0.000 claims description 12
229910052799 carbon Inorganic materials 0.000 claims description 12
150000003839 salts Chemical class 0.000 claims description 12
229910052760 oxygen Inorganic materials 0.000 claims description 10
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 10
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 9
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 9
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 9
125000002877 alkyl aryl group Chemical group 0.000 claims description 8
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
125000000623 heterocyclic group Chemical group 0.000 claims description 7
239000008194 pharmaceutical composition Substances 0.000 claims description 7
229910052717 sulfur Inorganic materials 0.000 claims description 7
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
150000001721 carbon Chemical group 0.000 claims description 5
229910052739 hydrogen Inorganic materials 0.000 claims description 5
229920006395 saturated elastomer Polymers 0.000 claims description 5
125000004432 carbon atom Chemical group C* 0.000 claims description 4
125000000753 cycloalkyl group Chemical group 0.000 claims description 4
125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 4
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 4
125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 4
LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 claims description 4
FLIBMJBCXIYACO-UHFFFAOYSA-N O=C1N(C=23)CCSC3=CC=CC=2C1(CC=1C=CN=CC=1)CC1=CC=NC=C1 Chemical compound O=C1N(C=23)CCSC3=CC=CC=2C1(CC=1C=CN=CC=1)CC1=CC=NC=C1 FLIBMJBCXIYACO-UHFFFAOYSA-N 0.000 claims description 3
125000003342 alkenyl group Chemical group 0.000 claims description 3
125000000304 alkynyl group Chemical group 0.000 claims description 3
125000002837 carbocyclic group Chemical group 0.000 claims description 3
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 3
125000001424 substituent group Chemical group 0.000 claims description 3
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 3
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
101100439663 Arabidopsis thaliana CHR7 gene Proteins 0.000 claims description 2
101100516563 Caenorhabditis elegans nhr-6 gene Proteins 0.000 claims description 2
101100079984 Caenorhabditis elegans nhr-9 gene Proteins 0.000 claims description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 2
IGCUPXWNFQFLAZ-UHFFFAOYSA-N O=C1N(C2=CC=CC=C2OC2=CC=C3)C2=C3C1(CC=1C=CN=CC=1)CC1=CC=NC=C1 Chemical compound O=C1N(C2=CC=CC=C2OC2=CC=C3)C2=C3C1(CC=1C=CN=CC=1)CC1=CC=NC=C1 IGCUPXWNFQFLAZ-UHFFFAOYSA-N 0.000 claims description 2
IDIGDAMPGZSRRL-UHFFFAOYSA-N O=C1N(C2=CC=CC=C2SC2=CC=C3)C2=C3C1(CC=1C=CN=CC=1)CC1=CC=NC=C1 Chemical compound O=C1N(C2=CC=CC=C2SC2=CC=C3)C2=C3C1(CC=1C=CN=CC=1)CC1=CC=NC=C1 IDIGDAMPGZSRRL-UHFFFAOYSA-N 0.000 claims description 2
125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 2
125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 claims description 2
101100440695 Dictyostelium discoideum corB gene Proteins 0.000 claims 3
101100203602 Hypocrea jecorina (strain QM6a) sor7 gene Proteins 0.000 claims 2
101100134929 Gallus gallus COR9 gene Proteins 0.000 claims 1
OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 abstract description 15
229960004373 acetylcholine Drugs 0.000 abstract description 14
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 9
201000010099 disease Diseases 0.000 abstract description 8
239000002858 neurotransmitter agent Substances 0.000 abstract description 6
239000000126 substance Substances 0.000 abstract description 5
230000019771 cognition Effects 0.000 abstract description 3
239000000543 intermediate Substances 0.000 abstract 1
230000001722 neurochemical effect Effects 0.000 abstract 1
239000002831 pharmacologic agent Substances 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 17
239000003814 drug Substances 0.000 description 17
239000000203 mixture Substances 0.000 description 16
229940079593 drug Drugs 0.000 description 13
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
238000001819 mass spectrum Methods 0.000 description 12
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 11
239000002585 base Substances 0.000 description 11
239000000243 solution Substances 0.000 description 11
229910001868 water Inorganic materials 0.000 description 11
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
239000004480 active ingredient Substances 0.000 description 10
238000006243 chemical reaction Methods 0.000 description 10
239000002904 solvent Substances 0.000 description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 9
239000002253 acid Substances 0.000 description 8
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
238000002360 preparation method Methods 0.000 description 8
208000024827 Alzheimer disease Diseases 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
230000006735 deficit Effects 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical class [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
229910000069 nitrogen hydride Inorganic materials 0.000 description 6
239000000047 product Substances 0.000 description 6
125000002619 bicyclic group Chemical group 0.000 description 5
229960001231 choline Drugs 0.000 description 5
150000002148 esters Chemical class 0.000 description 5
239000007788 liquid Substances 0.000 description 5
230000036651 mood Effects 0.000 description 5
206010028417 myasthenia gravis Diseases 0.000 description 5
229910052757 nitrogen Inorganic materials 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
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
238000005481 NMR spectroscopy Methods 0.000 description 4
208000018737 Parkinson disease Diseases 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
150000001450 anions Chemical class 0.000 description 4
125000004429 atom Chemical group 0.000 description 4
210000004556 brain Anatomy 0.000 description 4
239000002775 capsule Substances 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 4
230000001149 cognitive effect Effects 0.000 description 4
230000007812 deficiency Effects 0.000 description 4
230000000694 effects Effects 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
230000007658 neurological function Effects 0.000 description 4
LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
239000007787 solid Substances 0.000 description 4
239000003826 tablet Substances 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
238000004809 thin layer chromatography Methods 0.000 description 4
210000001519 tissue Anatomy 0.000 description 4
OPYKHUMNFAMIBL-NILKIKDOSA-L (2s)-2-[4-[4-[(2s)-2-hydroxy-4,4-dimethylmorpholin-4-ium-2-yl]phenyl]phenyl]-4,4-dimethylmorpholin-4-ium-2-ol;dibromide Chemical compound [Br-].[Br-].C1[N+](C)(C)CCO[C@@]1(O)C1=CC=C(C=2C=CC(=CC=2)[C@]2(O)OCC[N+](C)(C)C2)C=C1 OPYKHUMNFAMIBL-NILKIKDOSA-L 0.000 description 3
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 3
238000005160 1H NMR spectroscopy Methods 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
208000023105 Huntington disease Diseases 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
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 3
YEJCDKJIEMIWRQ-UHFFFAOYSA-N Linopirdine Chemical compound O=C1N(C=2C=CC=CC=2)C2=CC=CC=C2C1(CC=1C=CN=CC=1)CC1=CC=NC=C1 YEJCDKJIEMIWRQ-UHFFFAOYSA-N 0.000 description 3
208000036626 Mental retardation Diseases 0.000 description 3
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
208000012902 Nervous system disease Diseases 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
241000700159 Rattus Species 0.000 description 3
206010039966 Senile dementia Diseases 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
150000001408 amides Chemical class 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
230000001713 cholinergic effect Effects 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
238000004440 column chromatography Methods 0.000 description 3
239000003937 drug carrier Substances 0.000 description 3
238000009472 formulation Methods 0.000 description 3
239000007903 gelatin capsule Substances 0.000 description 3
150000002430 hydrocarbons Chemical group 0.000 description 3
239000008101 lactose Substances 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
230000003340 mental effect Effects 0.000 description 3
230000009251 neurologic dysfunction Effects 0.000 description 3
238000000746 purification Methods 0.000 description 3
230000002285 radioactive effect Effects 0.000 description 3
238000002390 rotary evaporation Methods 0.000 description 3
239000000741 silica gel Substances 0.000 description 3
229910002027 silica gel Inorganic materials 0.000 description 3
239000012312 sodium hydride Substances 0.000 description 3
229910000104 sodium hydride Inorganic materials 0.000 description 3
239000007858 starting material Substances 0.000 description 3
CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
229940124597 therapeutic agent Drugs 0.000 description 3
FKNQCJSGGFJEIZ-UHFFFAOYSA-N 4-methylpyridine Chemical compound CC1=CC=NC=C1 FKNQCJSGGFJEIZ-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
101150041968 CDC13 gene Proteins 0.000 description 2
206010012289 Dementia Diseases 0.000 description 2
108010010803 Gelatin Proteins 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 2
WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
208000005314 Multi-Infarct Dementia Diseases 0.000 description 2
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
229920002472 Starch Chemical class 0.000 description 2
201000004810 Vascular dementia Diseases 0.000 description 2
239000002168 alkylating agent Substances 0.000 description 2
229940100198 alkylating agent Drugs 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
229910021529 ammonia Inorganic materials 0.000 description 2
239000000010 aprotic solvent Substances 0.000 description 2
238000003556 assay Methods 0.000 description 2
HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 2
239000012267 brine Substances 0.000 description 2
239000001913 cellulose Chemical class 0.000 description 2
235000010980 cellulose Nutrition 0.000 description 2
229920002678 cellulose Chemical class 0.000 description 2
230000008859 change Effects 0.000 description 2
OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
239000007891 compressed tablet Substances 0.000 description 2
230000008878 coupling Effects 0.000 description 2
238000010168 coupling process Methods 0.000 description 2
238000005859 coupling reaction Methods 0.000 description 2
NLUNLVTVUDIHFE-UHFFFAOYSA-N cyclooctylcyclooctane Chemical compound C1CCCCCCC1C1CCCCCCC1 NLUNLVTVUDIHFE-UHFFFAOYSA-N 0.000 description 2
NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
230000003291 dopaminomimetic effect Effects 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
230000004064 dysfunction Effects 0.000 description 2
239000003623 enhancer Substances 0.000 description 2
239000008273 gelatin Substances 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
235000019322 gelatine Nutrition 0.000 description 2
235000011852 gelatine desserts Nutrition 0.000 description 2
239000008103 glucose Substances 0.000 description 2
125000005842 heteroatom Chemical group 0.000 description 2
238000000099 in vitro assay Methods 0.000 description 2
230000001965 increasing effect Effects 0.000 description 2
229910052943 magnesium sulfate Inorganic materials 0.000 description 2
235000019341 magnesium sulphate Nutrition 0.000 description 2
239000000463 material Substances 0.000 description 2
230000008018 melting Effects 0.000 description 2
238000002844 melting Methods 0.000 description 2
230000028161 membrane depolarization Effects 0.000 description 2
UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 2
125000002950 monocyclic group Chemical group 0.000 description 2
210000000653 nervous system Anatomy 0.000 description 2
208000015015 neurological dysfunction Diseases 0.000 description 2
230000000926 neurological effect Effects 0.000 description 2
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
LXCFILQKKLGQFO-UHFFFAOYSA-N p-hydroxybenzoic acid methyl ester Natural products COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
239000003182 parenteral nutrition solution Substances 0.000 description 2
239000011591 potassium Substances 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
238000010992 reflux Methods 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
239000003381 stabilizer Substances 0.000 description 2
239000008107 starch Chemical class 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
238000013268 sustained release Methods 0.000 description 2
239000012730 sustained-release form Substances 0.000 description 2
208000024891 symptom Diseases 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical compound C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 2
238000011269 treatment regimen Methods 0.000 description 2
RXPRRQLKFXBCSJ-GIVPXCGWSA-N vincamine Chemical compound C1=CC=C2C(CCN3CCC4)=C5[C@@H]3[C@]4(CC)C[C@](O)(C(=O)OC)N5C2=C1 RXPRRQLKFXBCSJ-GIVPXCGWSA-N 0.000 description 2
SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical compound C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 description 1
JPMRGPPMXHGKRO-UHFFFAOYSA-N 2-(chloromethyl)pyridine hydrochloride Chemical compound Cl.ClCC1=CC=CC=N1 JPMRGPPMXHGKRO-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
125000005986 4-piperidonyl group Chemical group 0.000 description 1
NWWWGAKVHCSAEU-UHFFFAOYSA-N 5-bromopentanenitrile Chemical compound BrCCCCC#N NWWWGAKVHCSAEU-UHFFFAOYSA-N 0.000 description 1
IGRMAAOTPDHXJN-UHFFFAOYSA-N 8-oxa-1-azatetracyclo[7.6.1.02,7.013,16]hexadeca-2,4,6,9,11,13(16)-hexaen-15-one Chemical compound O1C2=CC=CC=C2N2C(=O)CC3=CC=CC1=C32 IGRMAAOTPDHXJN-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
239000000275 Adrenocorticotropic Hormone Substances 0.000 description 1
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
238000006418 Brown reaction Methods 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
229940122041 Cholinesterase inhibitor Drugs 0.000 description 1
208000028698 Cognitive impairment Diseases 0.000 description 1
102400000739 Corticotropin Human genes 0.000 description 1
101800000414 Corticotropin Proteins 0.000 description 1
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-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
OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
238000005727 Friedel-Crafts reaction Methods 0.000 description 1
235000010469 Glycine max Nutrition 0.000 description 1
244000068988 Glycine max Species 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
206010061216 Infarction Diseases 0.000 description 1
239000007836 KH2PO4 Substances 0.000 description 1
229920005479 Lucite® Polymers 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
239000007832 Na2SO4 Substances 0.000 description 1
KBAFPSLPKGSANY-UHFFFAOYSA-N Naftidrofuryl Chemical compound C=1C=CC2=CC=CC=C2C=1CC(C(=O)OCCN(CC)CC)CC1CCCO1 KBAFPSLPKGSANY-UHFFFAOYSA-N 0.000 description 1
108090000189 Neuropeptides Proteins 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
BYPFEZZEUUWMEJ-UHFFFAOYSA-N Pentoxifylline Chemical compound O=C1N(CCCCC(=O)C)C(=O)N(C)C2=C1N(C)C=N2 BYPFEZZEUUWMEJ-UHFFFAOYSA-N 0.000 description 1
PIJVFDBKTWXHHD-UHFFFAOYSA-N Physostigmine Natural products C12=CC(OC(=O)NC)=CC=C2N(C)C2C1(C)CCN2C PIJVFDBKTWXHHD-UHFFFAOYSA-N 0.000 description 1
GMZVRMREEHBGGF-UHFFFAOYSA-N Piracetam Chemical compound NC(=O)CN1CCCC1=O GMZVRMREEHBGGF-UHFFFAOYSA-N 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 1
208000028017 Psychotic disease Diseases 0.000 description 1
241000700157 Rattus norvegicus Species 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
241000244317 Tillandsia usneoides Species 0.000 description 1
GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 description 1
108010004977 Vasopressins Proteins 0.000 description 1
102000002852 Vasopressins Human genes 0.000 description 1
ILXDAXZQNSOSAE-UHFFFAOYSA-N [AlH3].[Cl] Chemical compound [AlH3].[Cl] ILXDAXZQNSOSAE-UHFFFAOYSA-N 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000009471 action Effects 0.000 description 1
230000003213 activating effect Effects 0.000 description 1
230000004913 activation Effects 0.000 description 1
239000013543 active substance Substances 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
239000003513 alkali Substances 0.000 description 1
150000001336 alkenes Chemical class 0.000 description 1
125000003545 alkoxy group Chemical group 0.000 description 1
150000001350 alkyl halides Chemical class 0.000 description 1
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
230000003064 anti-oxidating effect Effects 0.000 description 1
KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 1
150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
229960000686 benzalkonium chloride Drugs 0.000 description 1
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
230000033228 biological regulation Effects 0.000 description 1
230000005540 biological transmission Effects 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
230000037396 body weight Effects 0.000 description 1
230000003925 brain function Effects 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
235000014121 butter Nutrition 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
235000011148 calcium chloride Nutrition 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
239000000969 carrier Substances 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
230000002490 cerebral effect Effects 0.000 description 1
PBKVEOSEPXMKDN-LZHUFOCISA-N chembl2311030 Chemical class CS(O)(=O)=O.CS(O)(=O)=O.CS(O)(=O)=O.CS(O)(=O)=O.C1=CC([C@H]2C[C@H](CN(C)[C@@H]2C2)C(=O)N[C@]3(C(=O)N4[C@H](C(N5CCC[C@H]5[C@]4(O)O3)=O)C(C)C)C(C)C)=C3C2=CNC3=C1.C1=CC([C@H]2C[C@H](CN(C)[C@@H]2C2)C(=O)N[C@]3(C(=O)N4[C@H](C(N5CCC[C@H]5[C@]4(O)O3)=O)C(C)CC)C(C)C)=C3C2=CNC3=C1.C1=CC([C@H]2C[C@H](CN(C)[C@@H]2C2)C(=O)N[C@]3(C(=O)N4[C@H](C(N5CCC[C@H]5[C@]4(O)O3)=O)CC(C)C)C(C)C)=C3C2=CNC3=C1.C([C@H]1C(=O)N2CCC[C@H]2[C@]2(O)O[C@](C(N21)=O)(NC(=O)[C@H]1CN(C)[C@H]2[C@@H](C=3C=CC=C4NC=C(C=34)C2)C1)C(C)C)C1=CC=CC=C1 PBKVEOSEPXMKDN-LZHUFOCISA-N 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
229960004926 chlorobutanol Drugs 0.000 description 1
239000000544 cholinesterase inhibitor Substances 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
238000000576 coating method Methods 0.000 description 1
229940075614 colloidal silicon dioxide Drugs 0.000 description 1
238000004040 coloring Methods 0.000 description 1
239000000470 constituent Substances 0.000 description 1
238000012937 correction Methods 0.000 description 1
230000001054 cortical effect Effects 0.000 description 1
IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 1
229960000258 corticotropin Drugs 0.000 description 1
235000012343 cottonseed oil Nutrition 0.000 description 1
239000002385 cottonseed oil Substances 0.000 description 1
239000007822 coupling agent Substances 0.000 description 1
239000013078 crystal Substances 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
XSYZCZPCBXYQTE-UHFFFAOYSA-N cyclodecylcyclodecane Chemical compound C1CCCCCCCCC1C1CCCCCCCCC1 XSYZCZPCBXYQTE-UHFFFAOYSA-N 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([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
125000004856 decahydroquinolinyl group Chemical group N1(CCCC2CCCCC12)* 0.000 description 1
230000005786 degenerative changes Effects 0.000 description 1
230000003412 degenerative effect Effects 0.000 description 1
239000008367 deionised water Substances 0.000 description 1
229910021641 deionized water Inorganic materials 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
238000004821 distillation Methods 0.000 description 1
RXPRRQLKFXBCSJ-UHFFFAOYSA-N dl-Vincamin Natural products C1=CC=C2C(CCN3CCC4)=C5C3C4(CC)CC(O)(C(=O)OC)N5C2=C1 RXPRRQLKFXBCSJ-UHFFFAOYSA-N 0.000 description 1
229960003638 dopamine Drugs 0.000 description 1
230000000857 drug effect Effects 0.000 description 1
230000002708 enhancing effect Effects 0.000 description 1
239000002532 enzyme inhibitor Substances 0.000 description 1
229940040520 ergoloid mesylates Drugs 0.000 description 1
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000000284 extract Substances 0.000 description 1
238000011049 filling Methods 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
239000012458 free base Substances 0.000 description 1
230000006870 function Effects 0.000 description 1
ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
230000004927 fusion Effects 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
239000011521 glass Substances 0.000 description 1
239000003365 glass fiber Substances 0.000 description 1
150000002334 glycols Chemical class 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
150000005826 halohydrocarbons Chemical class 0.000 description 1
230000036541 health Effects 0.000 description 1
150000002390 heteroarenes Chemical class 0.000 description 1
125000001072 heteroaryl group Chemical group 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical group O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
150000003949 imides Chemical class 0.000 description 1
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
125000004926 indolenyl group Chemical group 0.000 description 1
150000002476 indolines Chemical class 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
238000002372 labelling Methods 0.000 description 1
239000003041 laboratory chemical Substances 0.000 description 1
239000010410 layer Substances 0.000 description 1
229960004248 linopirdine Drugs 0.000 description 1
VVNXEADCOVSAER-UHFFFAOYSA-N lithium sodium Chemical compound [Li].[Na] VVNXEADCOVSAER-UHFFFAOYSA-N 0.000 description 1
JCIVHYBIFRUGKO-UHFFFAOYSA-N lithium;2,2,6,6-tetramethylpiperidine Chemical compound [Li].CC1(C)CCCC(C)(C)N1 JCIVHYBIFRUGKO-UHFFFAOYSA-N 0.000 description 1
WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 1
229960002216 methylparaben Drugs 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
239000012046 mixed solvent Substances 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
235000019796 monopotassium phosphate Nutrition 0.000 description 1
229960001132 naftidrofuryl Drugs 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
210000001640 nerve ending Anatomy 0.000 description 1
230000004776 neurological deficiency Effects 0.000 description 1
230000007971 neurological deficit Effects 0.000 description 1
230000003957 neurotransmitter release Effects 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
239000012454 non-polar solvent Substances 0.000 description 1
SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
229960002748 norepinephrine Drugs 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical class CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
125000004930 octahydroisoquinolinyl group Chemical group C1(NCCC2CCCC=C12)* 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
235000019629 palatability Nutrition 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
230000001936 parietal effect Effects 0.000 description 1
229960001476 pentoxifylline Drugs 0.000 description 1
210000001428 peripheral nervous system Anatomy 0.000 description 1
230000002572 peristaltic effect Effects 0.000 description 1
239000008177 pharmaceutical agent Substances 0.000 description 1
230000003285 pharmacodynamic effect Effects 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
238000003408 phase transfer catalysis Methods 0.000 description 1
150000003904 phospholipids Chemical class 0.000 description 1
150000004714 phosphonium salts Chemical group 0.000 description 1
125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
PIJVFDBKTWXHHD-HIFRSBDPSA-N physostigmine Chemical compound C12=CC(OC(=O)NC)=CC=C2N(C)[C@@H]2[C@@]1(C)CCN2C PIJVFDBKTWXHHD-HIFRSBDPSA-N 0.000 description 1
229960001697 physostigmine Drugs 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
229960005235 piperonyl butoxide Drugs 0.000 description 1
229960004526 piracetam Drugs 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
239000004926 polymethyl methacrylate Substances 0.000 description 1
IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000002243 precursor Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
229960003415 propylparaben Drugs 0.000 description 1
125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
230000002633 protecting effect Effects 0.000 description 1
238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000001422 pyrrolinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
150000003242 quaternary ammonium salts Chemical class 0.000 description 1
238000010791 quenching Methods 0.000 description 1
230000000171 quenching effect Effects 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
230000008707 rearrangement Effects 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000011160 research Methods 0.000 description 1
230000004044 response Effects 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
238000007127 saponification reaction Methods 0.000 description 1
238000003345 scintillation counting Methods 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
230000000862 serotonergic effect Effects 0.000 description 1
229940076279 serotonin Drugs 0.000 description 1
239000002002 slurry Substances 0.000 description 1
239000011734 sodium Substances 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
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
238000001179 sorption measurement Methods 0.000 description 1
229910001220 stainless steel Inorganic materials 0.000 description 1
239000010935 stainless steel Substances 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
238000003756 stirring Methods 0.000 description 1
230000008022 sublimation Effects 0.000 description 1
238000005092 sublimation method Methods 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000000725 suspension Substances 0.000 description 1
210000002504 synaptic vesicle Anatomy 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
238000012360 testing method Methods 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
230000002227 vasoactive effect Effects 0.000 description 1
229960003726 vasopressin Drugs 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
229960002726 vincamine Drugs 0.000 description 1
238000005303 weighing Methods 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/06—Peri-condensed systems
- 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
- A61P25/28—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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/06—Peri-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/06—Peri-condensed systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Chemical & Material Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Hospice & Palliative Care (AREA)
Psychiatry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

CA002146000A 1992-10-13 1993-10-12 Derives de substitution en 3,3 d'indolin-2-ones tri- et tetracycliques, utiles pour le traitement de troubles cognitifs Abandoned CA2146000A1 (fr)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US96052292A	1992-10-13	1992-10-13
US07/960,522		1992-10-13

Publications (1)

Publication Number	Publication Date
CA2146000A1 true CA2146000A1 (fr)	1994-04-28

Family

ID=25503278

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002146000A Abandoned CA2146000A1 (fr)	1992-10-13	1993-10-12	Derives de substitution en 3,3 d'indolin-2-ones tri- et tetracycliques, utiles pour le traitement de troubles cognitifs

Country Status (8)

Country	Link
EP (1)	EP0664810A1 (fr)
JP (1)	JPH08502293A (fr)
AU (1)	AU6242294A (fr)
CA (1)	CA2146000A1 (fr)
IL (1)	IL107251A0 (fr)
MX (1)	MX9306337A (fr)
WO (1)	WO1994009009A1 (fr)
ZA (1)	ZA937604B (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US7601856B2 (en)	2006-07-27	2009-10-13	Wyeth	Benzofurans as potassium ion channel modulators
CN112624972A (zh) *	2019-09-24	2021-04-09	中国人民解放军军事科学院军事医学研究院	吖啶酮类化合物及医药用途

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4760083A (en) *	1986-04-10	1988-07-26	E. I. Dupont De Nemours & Company	3,3-disubstituted indolines
US5173489A (en) *	1986-04-10	1992-12-22	The Dupont Merck Pharmaceutical Co.	α,α-disubstituted aromatics and heteroaromatics as cognition enhancers
US5278045A (en) *	1990-02-28	1994-01-11	Du Pont Merck Pharmaceutical Company	Method and compositions to screen compounds for enhancement of the cholinergic, dopaminergic and serotonergic function

1993
- 1993-10-12 WO PCT/US1993/009476 patent/WO1994009009A1/fr not_active Ceased
- 1993-10-12 EP EP93923238A patent/EP0664810A1/fr not_active Withdrawn
- 1993-10-12 IL IL107251A patent/IL107251A0/xx unknown
- 1993-10-12 AU AU62422/94A patent/AU6242294A/en not_active Abandoned
- 1993-10-12 JP JP6510082A patent/JPH08502293A/ja active Pending
- 1993-10-12 MX MX9306337A patent/MX9306337A/es unknown
- 1993-10-12 CA CA002146000A patent/CA2146000A1/fr not_active Abandoned
- 1993-10-13 ZA ZA937604A patent/ZA937604B/xx unknown

Also Published As

Publication number	Publication date
WO1994009009A1 (fr)	1994-04-28
MX9306337A (es)	1995-01-31
EP0664810A1 (fr)	1995-08-02
ZA937604B (en)	1995-04-13
JPH08502293A (ja)	1996-03-12
IL107251A0 (en)	1994-01-25
AU6242294A (en)	1994-05-09

Legal Events

Date	Code	Title	Description
1998-10-13	FZDE	Discontinued

Publication	Publication Date	Title
KR100798161B1 (ko)	2008-01-28	신경병적 또는 신경정신병적 장애의 치료에서 ｇｌｙｔ-1저해제로서 사용하기 위한 트라이아자-스피로피페리딘유도체
SK822002A3 (en)	2002-09-10	New compounds
KR100255414B1 (ko)	2000-05-01	글루탐산염 수용기 길항근으로서의 삼환 퀴녹살린디온
JPH11502861A (ja)	1999-03-09	サブスタンスｐアンタゴニストとしての置換ベンゾラクタム化合物
HUT65831A (en)	1994-07-28	Process for producing substituted 3-amino-quinuclidine derivatives and pharmaceutically acceptable salts
HUT65771A (en)	1994-07-28	Process for producing substituted 3-amino-quinuclidine derivatives and pharmaceutical compositions containing them
KR100756113B1 (ko)	2007-09-05	당뇨병 및 비만을 치료하기 위한 5ｈｔ2ｃ 수용체 작용물질
EP0241006A2 (fr)	1987-10-14	Indolines 3,3-disubstitués
US5296478A (en)	1994-03-22	1-substituted oxindoles as cognition enhancers
WO1998018798A1 (fr)	1998-05-07	Derives de la cytisine ou derives azabicycliques condenses avec la pyridone, leur preparation et leur utilisation dans le traitement des toxicomanies
CA2468705A1 (fr)	2003-06-05	Sels succiniques de 5,8,14-triazatetracyclo'10.3.1.0<2,11>.0<4,9>-hexadeca-2(11),3,5,7,9-pentaene et compositions pharmaceutiques associees
US6117889A (en)	2000-09-12	7-Azabicyclo-[2.2.1]-heptane and -heptene derivatives as analgesics and anti-inflammatory agents
CA2760837C (fr)	2018-04-03	7-([1,2,4]triazolo[1,5-.alpha.]pyridin-6-yl)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydroisoquinoline et son utilisation
US20160185758A1 (en)	2016-06-30	2-(Pyridin-2-yl)-1, 7-Diaza-Spiro [4.4] Nonane-6-One Compound as Voltage-Gated Sodium Channel Modulator
CA2144636A1 (fr)	1994-03-31	Derives de substitution en 3,3' de 1,3-dihydro-2h-pyrrolo[2,3-b]heterocycl-2-one, utiles pour le traitement des troubles de la cognitifs chez l'homme
CZ111497A3 (cs)	1998-01-14	Diazepinoindoly jako inhibitory fosfodiesterásy IV
IL97726A (en)	1994-12-29	Pharmaceutical compositions containing compounds with bridged and unbridged heterocyclic groups, spiro-connected with oxazoline and thiazoline groups, and some new such compounds
US20160184306A1 (en)	2016-06-30	Novel Pyrimidinyl-DiazoSpiro Compounds
HUT74380A (en)	1996-12-30	7-azabicyclo-[2.2.1]-heptane and -heptene derivatives pharmaceutical compositions containing them, and process for producing former compounds
KR100325276B1 (ko)	2002-09-25	강박반응장애치료제로서n-(피리디닐)-1h-인돌-1-아민을포함하는약제학적조성물
CA2146000A1 (fr)	1994-04-28	Derives de substitution en 3,3 d'indolin-2-ones tri- et tetracycliques, utiles pour le traitement de troubles cognitifs
JP2582799B2 (ja)	1997-02-19	置換ヘキサヒドロアリ−ルキノリジン類
AU2002334837B2 (en)	2007-03-15	Triazepine derivatives as neurotrophic agents
US6821993B1 (en)	2004-11-23	Triazepine derivatives as neurotrophic agents
US5519132A (en)	1996-05-21	Pyridine compounds