DD292909A5 - Verfahren zur herstellung neuer 2-(1-piperazinyl)-4-phenylcycloalkanopyridinderivate - Google Patents

Verfahren zur herstellung neuer 2-(1-piperazinyl)-4-phenylcycloalkanopyridinderivate Download PDF

Info

Publication number: DD292909A5
Authority: DD; German Democratic Republic
Prior art keywords: compound; formula; alkyl; piperazinyl; compounds
Prior art date: 1989-03-03

Application number

DD90338287A

Other languages

German (de)

English (en)

Inventor

Katsuhiko Hino

Naoki Kai

Masato Sakamoto

Tatsuya Kon

Makoto Oka

Kiyoshi Furukawa

Yoshiaki Ochi

Original Assignee

��@��@��Kk��Kk��

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.)

1989-03-03

Filing date

1990-03-01

Publication date

1991-08-14

1990-03-01 Application filed by ��@��@��Kk��Kk�� filed Critical ��@��@��Kk��Kk��

1991-08-14 Publication of DD292909A5 publication Critical patent/DD292909A5/de

Links

-1 1-PIPERAZINYL Chemical class 0.000 title claims description 76
238000004519 manufacturing process Methods 0.000 title abstract description 8
150000001875 compounds Chemical class 0.000 claims abstract description 136
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 41
238000002360 preparation method Methods 0.000 claims abstract description 39
238000000034 method Methods 0.000 claims abstract description 27
150000003839 salts Chemical class 0.000 claims abstract description 22
125000000217 alkyl group Chemical group 0.000 claims abstract description 20
125000005843 halogen group Chemical group 0.000 claims abstract description 14
125000001424 substituent group Chemical group 0.000 claims abstract description 14
239000002253 acid Substances 0.000 claims abstract description 13
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 12
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 10
125000002252 acyl group Chemical group 0.000 claims abstract description 8
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 6
230000008569 process Effects 0.000 claims abstract description 5
125000003107 substituted aryl group Chemical group 0.000 claims abstract description 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 4
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
125000003545 alkoxy group Chemical group 0.000 claims description 6
125000004429 atom Chemical group 0.000 claims description 5
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 5
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 5
238000007327 hydrogenolysis reaction Methods 0.000 claims description 3
QOPVNWQGBQYBBP-UHFFFAOYSA-N chloroethyl chloroformate Chemical compound CC(Cl)OC(Cl)=O QOPVNWQGBQYBBP-UHFFFAOYSA-N 0.000 claims description 2
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 2
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 claims description 2
229910014585 C2-Ce Inorganic materials 0.000 claims 1
239000003814 drug Substances 0.000 abstract description 9
229940079593 drug Drugs 0.000 abstract description 8
125000002947 alkylene group Chemical group 0.000 abstract description 6
230000000561 anti-psychotic effect Effects 0.000 abstract description 6
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 6
239000002249 anxiolytic agent Substances 0.000 abstract description 4
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 3
230000000949 anxiolytic effect Effects 0.000 abstract description 3
230000002490 cerebral effect Effects 0.000 abstract description 3
201000010099 disease Diseases 0.000 abstract description 3
239000001257 hydrogen Substances 0.000 abstract description 2
229910052739 hydrogen Inorganic materials 0.000 abstract description 2
125000006273 (C1-C3) alkyl group Chemical group 0.000 abstract 1
125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 1
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 abstract 1
125000000882 C2-C6 alkenyl group Chemical group 0.000 abstract 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 114
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 52
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 36
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 35
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 31
238000012360 testing method Methods 0.000 description 31
239000000047 product Substances 0.000 description 30
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
239000000203 mixture Substances 0.000 description 24
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 22
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
230000000694 effects Effects 0.000 description 21
239000007858 starting material Substances 0.000 description 21
239000002904 solvent Substances 0.000 description 19
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 18
239000000243 solution Substances 0.000 description 18
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 15
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 13
YPHMISFOHDHNIV-FSZOTQKASA-N cycloheximide Chemical compound C1[C@@H](C)C[C@H](C)C(=O)[C@@H]1[C@H](O)CC1CC(=O)NC(=O)C1 YPHMISFOHDHNIV-FSZOTQKASA-N 0.000 description 12
230000006872 improvement Effects 0.000 description 12
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 12
239000011541 reaction mixture Substances 0.000 description 12
230000002829 reductive effect Effects 0.000 description 12
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
238000006243 chemical reaction Methods 0.000 description 11
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 10
230000027455 binding Effects 0.000 description 10
239000011976 maleic acid Substances 0.000 description 10
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
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
241000699670 Mus sp. Species 0.000 description 9
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N Vilsmeier-Haack reagent Natural products CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
238000001816 cooling Methods 0.000 description 9
239000004615 ingredient Substances 0.000 description 9
238000002844 melting Methods 0.000 description 9
230000008018 melting Effects 0.000 description 9
CFFZDZCDUFSOFZ-UHFFFAOYSA-N 3,4-Dihydroxy-phenylacetic acid Chemical compound OC(=O)CC1=CC=C(O)C(O)=C1 CFFZDZCDUFSOFZ-UHFFFAOYSA-N 0.000 description 8
DUUGKQCEGZLZNO-UHFFFAOYSA-N 5-hydroxyindoleacetic acid Chemical compound C1=C(O)C=C2C(CC(=O)O)=CNC2=C1 DUUGKQCEGZLZNO-UHFFFAOYSA-N 0.000 description 8
241001465754 Metazoa Species 0.000 description 8
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 8
239000008187 granular material Substances 0.000 description 8
QRMZSPFSDQBLIX-UHFFFAOYSA-N homovanillic acid Chemical compound COC1=CC(CC(O)=O)=CC=C1O QRMZSPFSDQBLIX-UHFFFAOYSA-N 0.000 description 8
238000002347 injection Methods 0.000 description 8
239000007924 injection Substances 0.000 description 8
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
239000000126 substance Substances 0.000 description 8
ZTVXNUVIKIEUSZ-UHFFFAOYSA-N 2-(4-butylpiperazin-1-yl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine Chemical compound C1CN(CCCC)CCN1C1=CC(C=2C=CC(F)=CC=2)=C(CCCCCC2)C2=N1 ZTVXNUVIKIEUSZ-UHFFFAOYSA-N 0.000 description 7
206010047700 Vomiting Diseases 0.000 description 7
UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 7
229910052731 fluorine Inorganic materials 0.000 description 7
239000011777 magnesium Substances 0.000 description 7
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
239000003921 oil Substances 0.000 description 7
235000019198 oils Nutrition 0.000 description 7
102000005962 receptors Human genes 0.000 description 7
108020003175 receptors Proteins 0.000 description 7
229940076279 serotonin Drugs 0.000 description 7
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
230000008673 vomiting Effects 0.000 description 7
125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 6
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 6
229960004046 apomorphine Drugs 0.000 description 6
210000004556 brain Anatomy 0.000 description 6
239000002775 capsule Substances 0.000 description 6
229960003638 dopamine Drugs 0.000 description 6
125000001153 fluoro group Chemical group F* 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
239000002207 metabolite Substances 0.000 description 6
239000000825 pharmaceutical preparation Substances 0.000 description 6
229930000680 A04AD01 - Scopolamine Natural products 0.000 description 5
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 5
STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 5
241000699666 Mus <mouse, genus> Species 0.000 description 5
STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 5
230000002401 inhibitory effect Effects 0.000 description 5
229910000027 potassium carbonate Inorganic materials 0.000 description 5
235000011181 potassium carbonates Nutrition 0.000 description 5
238000010992 reflux Methods 0.000 description 5
STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 5
229960002646 scopolamine Drugs 0.000 description 5
QCVMDCCMDJIMAG-UHFFFAOYSA-N 2-(4-ethylpiperazin-1-yl)-4-(4-fluorophenyl)-6,7,8,9-tetrahydro-5h-cyclohepta[b]pyridine Chemical compound C1CN(CC)CCN1C1=CC(C=2C=CC(F)=CC=2)=C(CCCCC2)C2=N1 QCVMDCCMDJIMAG-UHFFFAOYSA-N 0.000 description 4
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 4
RSTRCQJVDPSJFM-UHFFFAOYSA-N 4-(4-ethylpiperazin-1-yl)-6-(4-fluorophenyl)-3-azatricyclo[6.2.1.02,7]undeca-2(7),3,5-triene Chemical compound C1CN(CC)CCN1C1=CC(C=2C=CC(F)=CC=2)=C(C2CC3CC2)C3=N1 RSTRCQJVDPSJFM-UHFFFAOYSA-N 0.000 description 4
NOKRRIRWUNTCCU-UHFFFAOYSA-N 4-(4-ethylpiperazin-1-yl)-6-(4-fluorophenyl)-3-azatricyclo[7.2.1.02,7]dodeca-2(7),3,5-triene Chemical compound C1CN(CC)CCN1C1=CC(C=2C=CC(F)=CC=2)=C(CC2CC3CC2)C3=N1 NOKRRIRWUNTCCU-UHFFFAOYSA-N 0.000 description 4
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 4
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
229920002153 Hydroxypropyl cellulose Polymers 0.000 description 4
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 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
230000003042 antagnostic effect Effects 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
125000003118 aryl group Chemical group 0.000 description 4
238000002425 crystallisation Methods 0.000 description 4
230000008025 crystallization Effects 0.000 description 4
239000003085 diluting agent Substances 0.000 description 4
239000012153 distilled water Substances 0.000 description 4
238000002474 experimental method Methods 0.000 description 4
239000001863 hydroxypropyl cellulose Substances 0.000 description 4
235000010977 hydroxypropyl cellulose Nutrition 0.000 description 4
239000008101 lactose Substances 0.000 description 4
239000003446 ligand Substances 0.000 description 4
239000012044 organic layer Substances 0.000 description 4
230000000506 psychotropic effect Effects 0.000 description 4
238000001953 recrystallisation Methods 0.000 description 4
WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 description 3
FBWPWWWZWKPJFL-UHFFFAOYSA-N 3-Methoxy-4-hydroxyphenylethyleneglycol Chemical compound COC1=CC(C(O)CO)=CC=C1O FBWPWWWZWKPJFL-UHFFFAOYSA-N 0.000 description 3
JAGTYIWCZPYSMZ-UHFFFAOYSA-N 4-phenyl-2-piperazin-1-yl-5,6,7,8-tetrahydroquinoline Chemical compound C1CCCC2=C1N=C(N1CCNCC1)C=C2C1=CC=CC=C1 JAGTYIWCZPYSMZ-UHFFFAOYSA-N 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
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
229920002261 Corn starch Polymers 0.000 description 3
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
208000026139 Memory 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
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
230000003542 behavioural effect Effects 0.000 description 3
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
229920002678 cellulose Polymers 0.000 description 3
239000001913 cellulose Substances 0.000 description 3
235000010980 cellulose Nutrition 0.000 description 3
230000008859 change Effects 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
238000007796 conventional method Methods 0.000 description 3
239000008120 corn starch Substances 0.000 description 3
229940099112 cornstarch Drugs 0.000 description 3
239000013078 crystal Substances 0.000 description 3
125000000753 cycloalkyl group Chemical group 0.000 description 3
239000003937 drug carrier Substances 0.000 description 3
238000001035 drying Methods 0.000 description 3
150000002170 ethers Chemical class 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
239000012458 free base Substances 0.000 description 3
230000007062 hydrolysis Effects 0.000 description 3
238000006460 hydrolysis reaction Methods 0.000 description 3
239000005457 ice water Substances 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
230000014759 maintenance of location Effects 0.000 description 3
235000010355 mannitol Nutrition 0.000 description 3
239000003176 neuroleptic agent Substances 0.000 description 3
230000000144 pharmacologic effect Effects 0.000 description 3
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
239000000843 powder Substances 0.000 description 3
238000010898 silica gel chromatography Methods 0.000 description 3
229960002920 sorbitol Drugs 0.000 description 3
230000002269 spontaneous effect Effects 0.000 description 3
238000012549 training Methods 0.000 description 3
QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
TULBDJVBFLZTMH-UHFFFAOYSA-N 1-[4,5-bis(4-fluorophenyl)-6-methylpyridin-2-yl]-4-phenylpiperazine Chemical compound C=1C=C(F)C=CC=1C=1C(C)=NC(N2CCN(CC2)C=2C=CC=CC=2)=CC=1C1=CC=C(F)C=C1 TULBDJVBFLZTMH-UHFFFAOYSA-N 0.000 description 2
AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 2
SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 2
QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 2
RVOXFMZBSIGMNH-UHFFFAOYSA-N 4-(4-fluorophenyl)-2-(4-pentylpiperazin-1-yl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine Chemical compound C1CN(CCCCC)CCN1C1=CC(C=2C=CC(F)=CC=2)=C(CCCCCC2)C2=N1 RVOXFMZBSIGMNH-UHFFFAOYSA-N 0.000 description 2
241000416162 Astragalus gummifer Species 0.000 description 2
ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical compound N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
241000282472 Canis lupus familiaris Species 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
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 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
229920001615 Tragacanth Polymers 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
230000007059 acute toxicity Effects 0.000 description 2
231100000403 acute toxicity Toxicity 0.000 description 2
125000005041 acyloxyalkyl group Chemical group 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 2
150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
125000006196 aroyl alkyl group Chemical group 0.000 description 2
125000005279 aryl sulfonyloxy group Chemical group 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
210000003298 dental enamel Anatomy 0.000 description 2
235000014113 dietary fatty acids Nutrition 0.000 description 2
239000000194 fatty acid Substances 0.000 description 2
229930195729 fatty acid Natural products 0.000 description 2
239000008103 glucose Substances 0.000 description 2
235000011187 glycerol Nutrition 0.000 description 2
229910052736 halogen Inorganic materials 0.000 description 2
150000002367 halogens Chemical group 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
230000001965 increasing effect Effects 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
150000002576 ketones Chemical class 0.000 description 2
229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 2
239000012528 membrane Substances 0.000 description 2
125000005948 methanesulfonyloxy group Chemical group 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
125000004193 piperazinyl group Chemical group 0.000 description 2
229920000137 polyphosphoric acid Polymers 0.000 description 2
239000011148 porous material Substances 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 2
125000000714 pyrimidinyl group Chemical group 0.000 description 2
230000004044 response Effects 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
DKGZKTPJOSAWFA-UHFFFAOYSA-N spiperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCC2(C(NCN2C=2C=CC=CC=2)=O)CC1 DKGZKTPJOSAWFA-UHFFFAOYSA-N 0.000 description 2
239000000725 suspension Substances 0.000 description 2
235000010487 tragacanth Nutrition 0.000 description 2
239000000196 tragacanth Substances 0.000 description 2
229940116362 tragacanth Drugs 0.000 description 2
239000008096 xylene Substances 0.000 description 2
VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
SKYZYDSNJIOXRL-BTQNPOSSSA-N (6ar)-6-methyl-5,6,6a,7-tetrahydro-4h-dibenzo[de,g]quinoline-10,11-diol;hydrochloride Chemical compound Cl.C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 SKYZYDSNJIOXRL-BTQNPOSSSA-N 0.000 description 1
KITJXMWIPMZSEV-BIKHMRJRSA-N (Z)-but-2-enedioic acid (E)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O KITJXMWIPMZSEV-BIKHMRJRSA-N 0.000 description 1
QSGQCBDICVAKHL-SPIKMXEPSA-N (Z)-but-2-enedioic acid pyridine Chemical compound C1=CC=NC=C1.OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O QSGQCBDICVAKHL-SPIKMXEPSA-N 0.000 description 1
QLSJOGIENLKPTF-WLHGVMLRSA-N (e)-but-2-enedioic acid;pyridine Chemical compound C1=CC=NC=C1.OC(=O)\C=C\C(O)=O QLSJOGIENLKPTF-WLHGVMLRSA-N 0.000 description 1
MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
CFCAOOFZWZFRBO-BTJKTKAUSA-N (z)-but-2-enedioic acid;4-(4-fluorophenyl)-2-(4-methyl-1,4-diazepan-1-yl)-6,7,8,9-tetrahydro-5h-cyclohepta[b]pyridine Chemical compound OC(=O)\C=C/C(O)=O.C1CN(C)CCCN1C1=CC(C=2C=CC(F)=CC=2)=C(CCCCC2)C2=N1 CFCAOOFZWZFRBO-BTJKTKAUSA-N 0.000 description 1
LNKDSWZTOGFUER-UHFFFAOYSA-N 1-(4-hydroxy-3-methylphenyl)ethane-1,2-diol Chemical compound CC1=CC(C(O)CO)=CC=C1O LNKDSWZTOGFUER-UHFFFAOYSA-N 0.000 description 1
ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
OLSSWOGFAAOHGT-UHFFFAOYSA-N 1-[4,5-bis(4-methoxyphenyl)-6-methylpyridin-2-yl]-4-phenylpiperazine Chemical compound C1=CC(OC)=CC=C1C1=CC(N2CCN(CC2)C=2C=CC=CC=2)=NC(C)=C1C1=CC=C(OC)C=C1 OLSSWOGFAAOHGT-UHFFFAOYSA-N 0.000 description 1
ANWKMJKJGIGEJK-UHFFFAOYSA-N 1-[4-[4-(4-fluorophenyl)-6,7,8,9-tetrahydro-5h-cyclohepta[b]pyridin-2-yl]-1,4-diazepan-1-yl]butan-1-one Chemical compound C1CN(C(=O)CCC)CCCN1C1=CC(C=2C=CC(F)=CC=2)=C(CCCCC2)C2=N1 ANWKMJKJGIGEJK-UHFFFAOYSA-N 0.000 description 1
CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 1
125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
125000006017 1-propenyl group Chemical group 0.000 description 1
JHQBHXWBDPGQBS-UHFFFAOYSA-N 2-(4-benzylpiperazin-1-yl)-4-phenyl-5,6,7,8-tetrahydroquinoline Chemical compound C=1C=CC=CC=1CN(CC1)CCN1C(N=C1CCCCC1=1)=CC=1C1=CC=CC=C1 JHQBHXWBDPGQBS-UHFFFAOYSA-N 0.000 description 1
VPXRTCJIFXSVGS-UHFFFAOYSA-N 2-(4-cyclopropylpiperazin-1-yl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine Chemical compound C1=CC(F)=CC=C1C1=CC(N2CCN(CC2)C2CC2)=NC2=C1CCCCCC2 VPXRTCJIFXSVGS-UHFFFAOYSA-N 0.000 description 1
QKDUGPAEQXMLRD-UHFFFAOYSA-N 2-(4-ethylpiperazin-1-yl)-4-phenyl-5,6,7,8-tetrahydroquinoline Chemical compound C1CN(CC)CCN1C1=CC(C=2C=CC=CC=2)=C(CCCC2)C2=N1 QKDUGPAEQXMLRD-UHFFFAOYSA-N 0.000 description 1
AWFYPPSBLUWMFQ-UHFFFAOYSA-N 2-[5-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]-1-(1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NN=C(O1)CC(=O)N1CC2=C(CC1)NN=C2 AWFYPPSBLUWMFQ-UHFFFAOYSA-N 0.000 description 1
125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
NVZXOYFYBDDAAG-UHFFFAOYSA-N 2-chloro-4-(2,4-difluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine Chemical compound FC1=CC(F)=CC=C1C1=CC(Cl)=NC2=C1CCCCCC2 NVZXOYFYBDDAAG-UHFFFAOYSA-N 0.000 description 1
BTBPUFOEUCRBDM-UHFFFAOYSA-N 2-chloro-4-(4-fluorophenyl)-5,6,7,8-tetrahydroquinoline Chemical compound C1=CC(F)=CC=C1C1=CC(Cl)=NC2=C1CCCC2 BTBPUFOEUCRBDM-UHFFFAOYSA-N 0.000 description 1
HPOIKUGIRMPSJB-UHFFFAOYSA-N 2-chloro-4-phenyl-5,6,7,8-tetrahydroquinoline Chemical compound C=12CCCCC2=NC(Cl)=CC=1C1=CC=CC=C1 HPOIKUGIRMPSJB-UHFFFAOYSA-N 0.000 description 1
SVDDJQGVOFZBNX-UHFFFAOYSA-N 2-chloroethyl carbonochloridate Chemical compound ClCCOC(Cl)=O SVDDJQGVOFZBNX-UHFFFAOYSA-N 0.000 description 1
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
OFCNTYBPPAQCRE-UHFFFAOYSA-N 3-(2-aminoethyl)-3h-indol-5-ol Chemical compound C1=C(O)C=C2C(CCN)C=NC2=C1 OFCNTYBPPAQCRE-UHFFFAOYSA-N 0.000 description 1
BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
LOJBBLDAJBJVBZ-UHFFFAOYSA-N 3-(4-fluorophenyl)-3-oxopropanenitrile Chemical compound FC1=CC=C(C(=O)CC#N)C=C1 LOJBBLDAJBJVBZ-UHFFFAOYSA-N 0.000 description 1
FPCCSQOGAWCVBH-PSQIVULCSA-N 3-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]-1,1,2,2-tetratritioethyl]-1h-quinazoline-2,4-dione Chemical compound O=C1NC2=CC=CC=C2C(=O)N1C([3H])([3H])C([3H])([3H])N(CC1)CCC1C(=O)C1=CC=C(F)C=C1 FPCCSQOGAWCVBH-PSQIVULCSA-N 0.000 description 1
WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-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
PECKFYLIMOYBFF-UHFFFAOYSA-N 4-(2,4-difluorophenyl)-2-(4-ethylpiperazin-1-yl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine Chemical compound C1CN(CC)CCN1C1=CC(C=2C(=CC(F)=CC=2)F)=C(CCCCCC2)C2=N1 PECKFYLIMOYBFF-UHFFFAOYSA-N 0.000 description 1
IKBVNUXVYGAEED-UHFFFAOYSA-N 4-(2,4-difluorophenyl)-2-(4-ethylpiperazin-1-yl)-6,7,8,9-tetrahydro-5h-cyclohepta[b]pyridine Chemical compound C1CN(CC)CCN1C1=CC(C=2C(=CC(F)=CC=2)F)=C(CCCCC2)C2=N1 IKBVNUXVYGAEED-UHFFFAOYSA-N 0.000 description 1
HRGHXFVRGBPASQ-UHFFFAOYSA-N 4-(2,4-difluorophenyl)-2-(4-methylpiperazin-1-yl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine Chemical compound C1CN(C)CCN1C1=CC(C=2C(=CC(F)=CC=2)F)=C(CCCCCC2)C2=N1 HRGHXFVRGBPASQ-UHFFFAOYSA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
KUKHRFJCELROJI-UHFFFAOYSA-N 4-(4-fluorophenyl)-2-(3-methylpiperazin-1-yl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridine Chemical compound C1CNC(C)CN1C1=CC(C=2C=CC(F)=CC=2)=C(CCCCCC2)C2=N1 KUKHRFJCELROJI-UHFFFAOYSA-N 0.000 description 1
PPCSPDBLDSCTNI-UHFFFAOYSA-N 4-(4-fluorophenyl)-2-piperazin-1-yl-5,6,7,8-tetrahydroquinoline Chemical compound C1=CC(F)=CC=C1C1=CC(N2CCNCC2)=NC2=C1CCCC2 PPCSPDBLDSCTNI-UHFFFAOYSA-N 0.000 description 1
SFWHMKGQAAPGGE-UHFFFAOYSA-N 4-[2-(4-ethylpiperazin-1-yl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridin-4-yl]phenol Chemical compound C(C)N1CCN(CC1)C1=CC(=C2C(=N1)CCCCCC2)C2=CC=C(C=C2)O SFWHMKGQAAPGGE-UHFFFAOYSA-N 0.000 description 1
BMRCKJADNRBXLB-UHFFFAOYSA-N 4-[3-(4-hydroxyphenyl)-2-methyl-6-(4-phenylpiperazin-1-yl)pyridin-4-yl]phenol Chemical compound C=1C=C(O)C=CC=1C=1C(C)=NC(N2CCN(CC2)C=2C=CC=CC=2)=CC=1C1=CC=C(O)C=C1 BMRCKJADNRBXLB-UHFFFAOYSA-N 0.000 description 1
KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 description 1
LORXGMHCFCGLEE-UHFFFAOYSA-N 4-phenyl-5,6,7,8-tetrahydro-1h-quinolin-2-one Chemical compound C1=2CCCCC=2NC(=O)C=C1C1=CC=CC=C1 LORXGMHCFCGLEE-UHFFFAOYSA-N 0.000 description 1
FAKCSODRKHQDBP-UHFFFAOYSA-N 6-(2,4-difluorophenyl)-4-(4-ethylpiperazin-1-yl)-3-azatricyclo[6.2.1.02,7]undeca-2(7),3,5-triene Chemical compound C1CN(CC)CCN1C1=CC(C=2C(=CC(F)=CC=2)F)=C(C2CC3CC2)C3=N1 FAKCSODRKHQDBP-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
208000019901 Anxiety disease Diseases 0.000 description 1
SJKWQPGVGFYKCH-SPIKMXEPSA-N C(\C=C/C(=O)O)(=O)O.C(\C=C/C(=O)O)(=O)O.CN1CCN(CC1)C1=CC(=C2C(=N1)CCCCCC2)C2=CC=C(C=C2)F Chemical compound C(\C=C/C(=O)O)(=O)O.C(\C=C/C(=O)O)(=O)O.CN1CCN(CC1)C1=CC(=C2C(=N1)CCCCCC2)C2=CC=C(C=C2)F SJKWQPGVGFYKCH-SPIKMXEPSA-N 0.000 description 1
LVGIKJXLHXWMRD-SPIKMXEPSA-N C(\C=C/C(=O)O)(=O)O.C(\C=C/C(=O)O)(=O)O.CN1CCN(CCC1)C1=CC(=C2C(=N1)CCCCCC2)C2=CC=C(C=C2)F Chemical compound C(\C=C/C(=O)O)(=O)O.C(\C=C/C(=O)O)(=O)O.CN1CCN(CCC1)C1=CC(=C2C(=N1)CCCCCC2)C2=CC=C(C=C2)F LVGIKJXLHXWMRD-SPIKMXEPSA-N 0.000 description 1
GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
229940126062 Compound A Drugs 0.000 description 1
229920000858 Cyclodextrin Polymers 0.000 description 1
229920001353 Dextrin Polymers 0.000 description 1
239000004375 Dextrin Substances 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
241001397104 Dima Species 0.000 description 1
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
NXTSCPSXAJIZJT-SPIKMXEPSA-N OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.C1CN(CC)CCN1C1=CC(C=2C=CC(F)=CC=2)=C(CCCCC2)C2=N1 Chemical compound OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.C1CN(CC)CCN1C1=CC(C=2C=CC(F)=CC=2)=C(CCCCC2)C2=N1 NXTSCPSXAJIZJT-SPIKMXEPSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
239000004372 Polyvinyl alcohol Substances 0.000 description 1
239000004373 Pullulan Substances 0.000 description 1
229920001218 Pullulan Polymers 0.000 description 1
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
229920002125 Sokalan® Polymers 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 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
GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
MNLAVFKVRUQAKW-UHFFFAOYSA-N VR nerve agent Chemical compound CCN(CC)CCSP(C)(=O)OCC(C)C MNLAVFKVRUQAKW-UHFFFAOYSA-N 0.000 description 1
LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
125000004423 acyloxy group Chemical group 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
150000008041 alkali metal carbonates Chemical class 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
125000003342 alkenyl group Chemical group 0.000 description 1
125000004183 alkoxy alkyl group Chemical group 0.000 description 1
125000004414 alkyl thio group Chemical group 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
125000000304 alkynyl group Chemical group 0.000 description 1
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
239000003708 ampul Substances 0.000 description 1
229940031955 anhydrous lanolin Drugs 0.000 description 1
238000010171 animal model Methods 0.000 description 1
230000003496 anti-amnesic effect Effects 0.000 description 1
230000000049 anti-anxiety effect Effects 0.000 description 1
230000036506 anxiety Effects 0.000 description 1
229960003990 apomorphine hydrochloride Drugs 0.000 description 1
125000003435 aroyl group Chemical group 0.000 description 1
238000003556 assay Methods 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
239000002585 base Substances 0.000 description 1
239000000440 bentonite Substances 0.000 description 1
229910000278 bentonite Inorganic materials 0.000 description 1
235000012216 bentonite Nutrition 0.000 description 1
SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
ZJRCIQAMTAINCB-UHFFFAOYSA-N benzoylacetonitrile Chemical compound N#CCC(=O)C1=CC=CC=C1 ZJRCIQAMTAINCB-UHFFFAOYSA-N 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
238000007664 blowing Methods 0.000 description 1
239000000872 buffer Substances 0.000 description 1
239000007853 buffer solution Substances 0.000 description 1
125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
235000001465 calcium Nutrition 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
239000008112 carboxymethyl-cellulose Substances 0.000 description 1
239000000969 carrier Substances 0.000 description 1
238000010531 catalytic reduction reaction Methods 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
230000001713 cholinergic effect Effects 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
239000002475 cognitive enhancer Substances 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
125000001316 cycloalkyl alkyl 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
125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 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
NKLCHDQGUHMCGL-UHFFFAOYSA-N cyclohexylidenemethanone Chemical group O=C=C1CCCCC1 NKLCHDQGUHMCGL-UHFFFAOYSA-N 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
125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
235000019425 dextrin Nutrition 0.000 description 1
IBDMRHDXAQZJAP-UHFFFAOYSA-N dichlorophosphorylbenzene Chemical compound ClP(Cl)(=O)C1=CC=CC=C1 IBDMRHDXAQZJAP-UHFFFAOYSA-N 0.000 description 1
SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
238000000835 electrochemical detection Methods 0.000 description 1
238000000921 elemental analysis Methods 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
239000008098 formaldehyde solution Substances 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
FCRIOPQKJNGNNX-UHFFFAOYSA-N formic acid;propan-2-one Chemical compound OC=O.CC(C)=O FCRIOPQKJNGNNX-UHFFFAOYSA-N 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
ZLMMZGQMLSEFMO-UHFFFAOYSA-N furan-2-yl-[4-(4-phenyl-5,6,7,8-tetrahydroquinolin-2-yl)piperazin-1-yl]methanone Chemical compound C=1C=COC=1C(=O)N(CC1)CCN1C(N=C1CCCCC1=1)=CC=1C1=CC=CC=C1 ZLMMZGQMLSEFMO-UHFFFAOYSA-N 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000003365 glass fiber Substances 0.000 description 1
235000001727 glucose Nutrition 0.000 description 1
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000005223 heteroarylcarbonyl group Chemical group 0.000 description 1
125000005842 heteroatom Chemical group 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
150000004050 homopiperazines Chemical group 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
239000001341 hydroxy propyl starch Substances 0.000 description 1
125000002768 hydroxyalkyl group Chemical group 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
235000013828 hydroxypropyl starch Nutrition 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000002329 infrared spectrum Methods 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 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
125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
ZUBZATZOEPUUQF-UHFFFAOYSA-N isopropylhexane Natural products CCCCCCC(C)C ZUBZATZOEPUUQF-UHFFFAOYSA-N 0.000 description 1
125000005956 isoquinolyl group Chemical group 0.000 description 1
231100000225 lethality Toxicity 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
150000002632 lipids Chemical class 0.000 description 1
239000007788 liquid Substances 0.000 description 1
231100000053 low toxicity Toxicity 0.000 description 1
229960003511 macrogol Drugs 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
239000000463 material Substances 0.000 description 1
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
125000002950 monocyclic group Chemical group 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
210000000653 nervous system Anatomy 0.000 description 1
230000000701 neuroleptic effect Effects 0.000 description 1
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
150000002871 norepinephrines Chemical class 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
239000001301 oxygen Chemical group 0.000 description 1
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
229950008882 polysorbate Drugs 0.000 description 1
229920000136 polysorbate Polymers 0.000 description 1
229920002451 polyvinyl alcohol Polymers 0.000 description 1
235000019422 polyvinyl alcohol Nutrition 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
235000015497 potassium bicarbonate Nutrition 0.000 description 1
239000011736 potassium bicarbonate Substances 0.000 description 1
229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 1
229960001289 prazosin Drugs 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
230000002265 prevention Effects 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
238000000159 protein binding assay Methods 0.000 description 1
LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
239000003196 psychodysleptic agent Substances 0.000 description 1
235000019423 pullulan Nutrition 0.000 description 1
150000003222 pyridines Chemical class 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
230000002285 radioactive effect Effects 0.000 description 1
238000001525 receptor binding assay Methods 0.000 description 1
239000012266 salt solution Substances 0.000 description 1
HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
229960004499 scopolamine hydrobromide Drugs 0.000 description 1
WTGQALLALWYDJH-MOUKNHLCSA-N scopolamine hydrobromide (anhydrous) Chemical compound Br.C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 WTGQALLALWYDJH-MOUKNHLCSA-N 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
230000035939 shock Effects 0.000 description 1
RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
235000012239 silicon dioxide Nutrition 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
235000010356 sorbitol Nutrition 0.000 description 1
230000009870 specific binding Effects 0.000 description 1
229950001675 spiperone Drugs 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
238000003756 stirring Methods 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
229910052717 sulfur Chemical group 0.000 description 1
239000011593 sulfur Chemical group 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
238000012956 testing procedure Methods 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
238000001665 trituration Methods 0.000 description 1
238000002211 ultraviolet spectrum Methods 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
229920002554 vinyl polymer Polymers 0.000 description 1
239000001993 wax Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/22—Bridged ring systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

DD90338287A 1989-03-03 1990-03-01 Verfahren zur herstellung neuer 2-(1-piperazinyl)-4-phenylcycloalkanopyridinderivate DD292909A5 (de)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
JP5254489		1989-03-03

Publications (1)

Publication Number	Publication Date
DD292909A5 true DD292909A5 (de)	1991-08-14

Family

ID=12917732

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DD90338287A DD292909A5 (de)	1989-03-03	1990-03-01	Verfahren zur herstellung neuer 2-(1-piperazinyl)-4-phenylcycloalkanopyridinderivate

Country Status (15)

Country	Link
US (1)	US5021421A (no)
EP (1)	EP0385237B1 (no)
KR (1)	KR0149649B1 (no)
AT (1)	ATE107922T1 (no)
AU (1)	AU623981B2 (no)
CA (1)	CA2011346C (no)
DD (1)	DD292909A5 (no)
DE (1)	DE69010232T2 (no)
DK (1)	DK0385237T3 (no)
ES (1)	ES2058630T3 (no)
FI (1)	FI94413C (no)
HK (1)	HK1005872A1 (no)
HU (1)	HU204810B (no)
NO (1)	NO177095C (no)
RU (1)	RU2075478C1 (no)

Families Citing this family (49)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5041443A (en) *	1989-02-21	1991-08-20	Dainippon Pharmaceutical Co., Ltd.	Medicament for treating cerebral insufficiency diseases, novel 2-(1-piperazinyl)-4-phenylcycloalkanopyrimidine derivatives, and process for the production thereof
KR100307660B1 (ko) *	1993-06-25	2001-12-28	스즈키 츠네시	도파민재소비저해제
CA2144669A1 (en)	1994-03-29	1995-09-30	Kozo Akasaka	Biphenyl derivatives
US6458789B1 (en) *	1999-09-29	2002-10-01	Lion Bioscience Ag	2-aminopyridine derivatives and combinatorial libraries thereof
IL162859A0 (en) *	2002-02-05	2005-11-20	Novo Nordisk As	Novel aryl-and heteroarylpiperazines
AU2006228378A1 (en)	2005-03-31	2006-10-05	Pfizer Products Inc.	Cyclopentapyridine and tetrahydroquinoline derivatives
JP5121707B2 (ja)	2005-07-04	2013-01-16	ハイポイントファーマシューティカルズ，エルエルシー	新規医薬
CA2653062A1 (en)	2006-05-23	2007-11-29	Transtech Pharma, Inc.	6- (4-cyclopropylpiperazin-1-yl) -2 ' -methyl- [3, 4 ' ] -bipyridine and its use as a medicament
CN102295606A (zh)	2006-05-29	2011-12-28	高点制药有限责任公司	合成3-（1，3-苯并间二氧杂环戊烯-5-基）-6-（4-环丙基哌嗪-1-基）-哒嗪的方法及其适用的中间体
US8354121B2 (en)	2006-06-09	2013-01-15	Dainippon Sumitomo Pharma Co., Ltd.	Tape preparation
DK2049529T3 (da) *	2006-07-14	2010-11-29	Merck Sharp & Dohme	Substituerede diazepan-orexin-receptor- antagonister
RS55585B1 (sr)	2006-11-22	2017-06-30	Clinical Research Associates LLC	Postupci za lečenje daunovog sindroma, krhkog x sindroma i autizma
EP2014656A3 (en)	2007-06-11	2011-08-24	High Point Pharmaceuticals, LLC	New heteocyclic h3 antagonists
CN101531634B (zh) *	2008-03-10	2013-09-18	北京德众万全医药科技有限公司	一种高纯度的布南色林及其制备方法
CN101530412A (zh) *	2008-03-10	2009-09-16	北京德众万全医药科技有限公司	一种布南色林的药物组合物及其制备方法
CN101747272B (zh) *	2008-12-02	2012-11-28	浙江华海药业股份有限公司	布南色林晶型b及其制备方法
CN101747273B (zh) *	2008-12-02	2012-03-07	浙江华海药业股份有限公司	布南色林中间体的制备方法
CN101766626B (zh) *	2008-12-30	2012-03-07	丽珠医药集团股份有限公司	一种治疗精神分裂症的含布南色林的口服制剂
US20120121515A1 (en)	2009-03-13	2012-05-17	Lenny Dang	Methods and compositions for cell-proliferation-related disorders
LT2448582T (lt)	2009-06-29	2017-07-10	Agios Pharmaceuticals, Inc.	Chinolin-8-sulfonamido dariniai, turintys priešvėžinį aktyvumą
CN101619039B (zh) *	2009-06-30	2011-04-13	严洁	2-(4-乙基-1-哌嗪基)-4-(4-氟苯基)-5,6,7,8,9,10-六氢芳辛并[b]吡啶及其组合物
CA2793836C (en)	2009-10-21	2020-03-24	Agios Pharmaceuticals, Inc.	Methods and compositions for cell-proliferation-related disorders
CA2793835C (en)	2009-10-21	2021-07-20	Agios Pharmaceuticals, Inc.	Methods and compositions for cell-proliferation-related disorders
US20130143897A1 (en)	2010-08-10	2013-06-06	Lupin Limited	Oral controlled release pharmaceutical compositions of blonanserin
CN102372673B (zh) *	2010-08-27	2014-04-09	天津市医药集团技术发展有限公司	布南色林结晶及其制备方法
CN102093289B (zh) *	2010-10-29	2012-12-19	常州华生制药有限公司	布南色林中间体的制备方法
CN102030707A (zh) *	2010-11-12	2011-04-27	深圳万和制药有限公司	布南色林中间体的制备方法
HUE065700T2 (hu)	2011-05-03	2024-06-28	Agios Pharmaceuticals Inc	Piruvát-kináz aktivátorok terápiában történõ alkalmazásra
CN102827170A (zh) *	2011-06-17	2012-12-19	安吉奥斯医药品有限公司	治疗活性组合物和它们的使用方法
CN102827073A (zh)	2011-06-17	2012-12-19	安吉奥斯医药品有限公司	治疗活性组合物和它们的使用方法
CN104114543B (zh)	2012-01-06	2019-03-15	安吉奥斯医药品有限公司	治疗活性化合物及其使用方法
US9474779B2 (en)	2012-01-19	2016-10-25	Agios Pharmaceuticals, Inc.	Therapeutically active compositions and their methods of use
MX365747B (es)	2012-10-15	2019-06-12	Agios Pharmaceuticals Inc	Compuestos derivados de diarilurea de sulfonamida de arilo y sus usos.
WO2015003360A2 (en)	2013-07-11	2015-01-15	Agios Pharmaceuticals, Inc.	Therapeutically active compounds and their methods of use
EP3019480B1 (en)	2013-07-11	2020-05-06	Agios Pharmaceuticals, Inc.	2,4- or 4,6-diaminopyrimidine compounds as idh2 mutants inhibitors for the treatment of cancer
WO2015003355A2 (en)	2013-07-11	2015-01-15	Agios Pharmaceuticals, Inc.	Therapeutically active compounds and their methods of use
US9579324B2 (en)	2013-07-11	2017-02-28	Agios Pharmaceuticals, Inc	Therapeutically active compounds and their methods of use
US20150031627A1 (en)	2013-07-25	2015-01-29	Agios Pharmaceuticals, Inc	Therapeutically active compounds and their methods of use
WO2015138839A1 (en)	2014-03-14	2015-09-17	Agios Pharmaceuticals, Inc.	Pharmaceutical compositions of therapeutically active compounds
CN104311487B (zh) *	2014-09-22	2016-08-24	江苏正大丰海制药有限公司	一种布南色林晶型及其制备方法
LT3307271T (lt)	2015-06-11	2023-10-25	Agios Pharmaceuticals, Inc.	Piruvatkinazės aktyvatorių panaudojimo būdai
DK3362065T3 (da)	2015-10-15	2024-06-17	Servier Lab	Kombinationsbehandling omfattende ivosidenib, cytarabin og daunorubicin eller idarubicin til behandling af akut myeloid leukæmi
MX2018004586A (es)	2015-10-15	2018-08-16	Agios Pharmaceuticals Inc	Terapia de combinacion para tratar tumores malignos.
KR20190028109A (ko)	2017-09-08	2019-03-18	연성정밀화학(주)	블로난세린 함유 서방성 제제
CN110575438A (zh) *	2018-06-07	2019-12-17	湖南省湘中制药有限公司	一种布南色林固体分散体的制备及其应用
US10980788B2 (en)	2018-06-08	2021-04-20	Agios Pharmaceuticals, Inc.	Therapy for treating malignancies
KR20210139317A (ko)	2019-03-13	2021-11-22	오츠카 세이야쿠 가부시키가이샤	2급 아민을 함유하는 화합물의 아민 부분에 중수소 저급 알킬을 도입하는 방법
CN113698346A (zh) *	2020-05-22	2021-11-26	湖南省湘中制药有限公司	一种布南色林工艺杂质b的制备方法
CN113698347A (zh) *	2020-05-22	2021-11-26	湖南省湘中制药有限公司	一种布南色林工艺杂质f的制备方法

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS54128588A (en) *	1978-03-29	1979-10-05	Dainippon Pharmaceut Co Ltd	Antidepressive drugs consisting mainly of 2-(1-piperazinyl)- 4-phenylquinoline
DE3124673A1 (de) *	1981-06-24	1983-01-13	Bayer Ag, 5090 Leverkusen	Subsituierte 2-amino-pyridinderivate, verfahren zu ihrer herstellung, ihre verwendung in arzneimitteln, sowie deren herstellung
FR2602771B1 (fr) *	1986-08-12	1988-11-04	Rhone Poulenc Sante	Nouveaux derives de la benzyl-4 piperazine, leur preparation et les compositions pharmaceutiques qui les contiennent

1990
- 1990-02-20 EP EP90103244A patent/EP0385237B1/en not_active Expired - Lifetime
- 1990-02-20 DK DK90103244.1T patent/DK0385237T3/da active
- 1990-02-20 AT AT90103244T patent/ATE107922T1/de not_active IP Right Cessation
- 1990-02-20 DE DE69010232T patent/DE69010232T2/de not_active Expired - Lifetime
- 1990-02-20 ES ES90103244T patent/ES2058630T3/es not_active Expired - Lifetime
- 1990-02-20 US US07/481,183 patent/US5021421A/en not_active Expired - Lifetime
- 1990-03-01 AU AU50604/90A patent/AU623981B2/en not_active Expired
- 1990-03-01 NO NO900991A patent/NO177095C/no not_active IP Right Cessation
- 1990-03-01 FI FI901030A patent/FI94413C/fi active IP Right Grant
- 1990-03-01 DD DD90338287A patent/DD292909A5/de unknown
- 1990-03-02 HU HU901275A patent/HU204810B/hu unknown
- 1990-03-02 CA CA002011346A patent/CA2011346C/en not_active Expired - Lifetime
- 1990-03-03 KR KR1019900002874A patent/KR0149649B1/ko not_active IP Right Cessation
1992
- 1992-11-12 RU RU92004429/04A patent/RU2075478C1/ru active
1998
- 1998-06-05 HK HK98105004A patent/HK1005872A1/xx not_active IP Right Cessation

Also Published As

Publication number	Publication date
ATE107922T1 (de)	1994-07-15
EP0385237A2 (en)	1990-09-05
DK0385237T3 (da)	1994-07-25
NO177095C (no)	1995-07-19
HU204810B (en)	1992-02-28
EP0385237B1 (en)	1994-06-29
HU901275D0 (en)	1990-05-28
FI94413B (fi)	1995-05-31
ES2058630T3 (es)	1994-11-01
FI94413C (fi)	1995-09-11
AU5060490A (en)	1990-09-06
NO900991L (no)	1990-09-04
US5021421A (en)	1991-06-04
RU2075478C1 (ru)	1997-03-20
DE69010232D1 (de)	1994-08-04
EP0385237A3 (en)	1991-03-20
HK1005872A1 (en)	1999-01-29
FI901030A0 (fi)	1990-03-01
CA2011346A1 (en)	1990-09-03
HUT53361A (en)	1990-10-28
NO177095B (no)	1995-04-10
CA2011346C (en)	1999-08-03
KR900014358A (ko)	1990-10-23
DE69010232T2 (de)	1994-12-01
NO900991D0 (no)	1990-03-01
AU623981B2 (en)	1992-05-28
KR0149649B1 (ko)	1998-10-15

Publication	Publication Date	Title
DD292909A5 (de)	1991-08-14	Verfahren zur herstellung neuer 2-(1-piperazinyl)-4-phenylcycloalkanopyridinderivate
DE60218037T2 (de)	2007-08-23	Neue indolderivate mit affinität zum 5-ht6-rezeptor
DE68914515T2 (de)	1994-08-18	4-Amino-chinoline und Naphthyridine, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel.
DE60300021T2 (de)	2005-09-08	que-
DD297819A5 (de)	1992-01-23	Verfahren zur herstellung von 2-(1-piperazinyl)-4-phenylcycloalkanopyrimidinderivaten
DE1770305A1 (de)	1971-10-21	Neue substituierte Piperazine,Piperidine und Pyridine und Verfahren zu ihrer Herstellung
DE69919171T2 (de)	2005-08-04	Muskarin-rezeptor antagonisten
KR0155543B1 (ko)	1998-11-16	1-[모노-또는 비스(트리플루오로메틸)-2-피리디닐]피페라진을 함유한 약학조성물
DE60118956T2 (de)	2007-03-15	Calciumkanalantagonisten vom n-typ zur behandlung von schmerzen
DE3248138C2 (no)	1992-12-10
DE4430639A1 (de)	1996-03-07	Verwendung von 5-substituierten Pyridin- und Hexahydrochinolin-3-carbonsäurederivaten
DE69733427T2 (de)	2006-04-27	Tetrahydrobezindol derivate
DE2363052A1 (de)	1974-07-11	3-phenyl-3-aminoalkyl-2,6-dioxo-tetraund -hexahydropyridine, verfahren zu ihrer herstellung und ihre verwendung in pharmazeutischen zubereitungen
DE69521037T2 (de)	2001-10-25	Chinazolinylamino derivate mit alfa-antagonist wirkung
DE69207301T2 (de)	1996-08-29	Substituierte 3-Piperazinylalkyl 2,3-Dihydro-4H-1,3-Benzoxazin-4-One, deren Herstellung und Verwendung in Heilkunde
DE69232484T2 (de)	2002-10-31	Hydroisochinolinderivate
DE69612753T2 (de)	2005-07-07	(r)-5-bromo-n-(1-ethyl-4-methylhexahydro-1h-1,4-diazepin-6-yl)-2-methoxy-6-methylamino-3-pyridincarboxamid, verfahren zu seinerherstellung und dieses enthaltende medizinische zubereitung
DE3615180C2 (de)	1996-03-07	Disubstituierte 1,4-Piperazinylderivate, Verfahren zu deren Herstellung und diese Verbindungen enthaltende pharmazeutische Mittel
DE68910922T2 (de)	1994-03-17	Pyridyl- und Pyrimidinylderivate.
JPH0747574B2 (ja)	1995-05-24	ピリジン誘導体及びそれを有効成分とする向精神剤
DE69919575T2 (de)	2005-09-29	Benzoxazolderivate und medikamente die diese als aktiven wirkstoff enthalten
DE69629931T2 (de)	2004-07-29	1-(hetero)aryl-4-(kondensiertes thiazol-2-ylalkyl)-piperazin derivate, deren herstellung und deren verwendung in der behandlung von 5-ht1a-rezeptor vermittelten krankheiten
DE19746612A1 (de)	1999-04-29	2-Substituierte 1,2-Benzisothiazol-Derivate, ihre Herstellung und Verwendung
DE2817924A1 (de)	1978-11-02	3-(1-piperazinyl)-1,2,4-benzotriazine und ihre n-oxide
DE60204046T2 (de)	2006-01-19	N-heterocyclylhydrazide als neurotrophe mittel