JP5242871B2 - Ｎ−（インドールカルボニル）ピペラジン誘導体 - Google Patents
Ｎ−（インドールカルボニル）ピペラジン誘導体 Download PDFInfo
- Publication number
- JP5242871B2 JP5242871B2 JP2001512519A JP2001512519A JP5242871B2 JP 5242871 B2 JP5242871 B2 JP 5242871B2 JP 2001512519 A JP2001512519 A JP 2001512519A JP 2001512519 A JP2001512519 A JP 2001512519A JP 5242871 B2 JP5242871 B2 JP 5242871B2
- Authority
- JP
- Japan
- Prior art keywords
- methanone
- indol
- piperazin
- fluorophenethyl
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- FIVCRRVYLAXYFC-UHFFFAOYSA-N 1h-indol-2-yl(piperazin-1-yl)methanone Chemical class C=1C2=CC=CC=C2NC=1C(=O)N1CCNCC1 FIVCRRVYLAXYFC-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 87
- -1 R 4 is Inorganic materials 0.000 claims description 79
- 150000003839 salts Chemical class 0.000 claims description 18
- 239000002253 acid Substances 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 239000012453 solvate Substances 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 229910052740 iodine Inorganic materials 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- AQRLDDAFYYAIJP-UHFFFAOYSA-N Pruvanserin Chemical compound C1=CC(F)=CC=C1CCN1CCN(C(=O)C=2C=3NC=C(C=3C=CC=2)C#N)CC1 AQRLDDAFYYAIJP-UHFFFAOYSA-N 0.000 claims description 3
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 3
- YEFBQDDQIMYYAZ-UHFFFAOYSA-N (2,3-dimethyl-1h-indol-7-yl)-[4-[2-(4-fluorophenyl)ethyl]piperazin-1-yl]methanone Chemical compound C1=CC=C2C(C)=C(C)NC2=C1C(=O)N(CC1)CCN1CCC1=CC=C(F)C=C1 YEFBQDDQIMYYAZ-UHFFFAOYSA-N 0.000 claims description 2
- HFGRCURKGSRTFM-UHFFFAOYSA-N 1h-indol-6-yl-[4-(2-thiophen-2-ylethyl)piperazin-1-yl]methanone Chemical compound C=1C=C2C=CNC2=CC=1C(=O)N(CC1)CCN1CCC1=CC=CS1 HFGRCURKGSRTFM-UHFFFAOYSA-N 0.000 claims description 2
- ZOLKXPULEJPJSO-UHFFFAOYSA-N 4-[4-[2-(2-fluorophenyl)ethyl]piperazine-1-carbonyl]-1h-indole-3-carbonitrile Chemical compound FC1=CC=CC=C1CCN1CCN(C(=O)C=2C=3C(C#N)=CNC=3C=CC=2)CC1 ZOLKXPULEJPJSO-UHFFFAOYSA-N 0.000 claims description 2
- CAVIGCCPYOTFDV-UHFFFAOYSA-N 4-[4-[2-(4-fluorophenyl)ethyl]piperazine-1-carbonyl]-1h-indole-3-carbonitrile Chemical compound C1=CC(F)=CC=C1CCN1CCN(C(=O)C=2C=3C(C#N)=CNC=3C=CC=2)CC1 CAVIGCCPYOTFDV-UHFFFAOYSA-N 0.000 claims description 2
- MTRQQFRDXNSWJR-UHFFFAOYSA-N 5-[4-[2-(4-fluorophenyl)ethyl]piperazine-1-carbonyl]-1h-indole-3-carbaldehyde Chemical compound C1=CC(F)=CC=C1CCN1CCN(C(=O)C=2C=C3C(C=O)=CNC3=CC=2)CC1 MTRQQFRDXNSWJR-UHFFFAOYSA-N 0.000 claims description 2
- ILEABBIDWSYPMB-UHFFFAOYSA-N 5-[4-[2-(4-fluorophenyl)ethyl]piperazine-1-carbonyl]-1h-indole-3-carbonitrile Chemical compound C1=CC(F)=CC=C1CCN1CCN(C(=O)C=2C=C3C(C#N)=CNC3=CC=2)CC1 ILEABBIDWSYPMB-UHFFFAOYSA-N 0.000 claims description 2
- NPTKQTHTZFKGFD-UHFFFAOYSA-N 6-[4-[2-(4-fluorophenyl)ethyl]piperazine-1-carbonyl]-1h-indole-3-carbaldehyde Chemical compound C1=CC(F)=CC=C1CCN1CCN(C(=O)C=2C=C3NC=C(C=O)C3=CC=2)CC1 NPTKQTHTZFKGFD-UHFFFAOYSA-N 0.000 claims description 2
- ZZDGTNIPZHMQHT-UHFFFAOYSA-N 6-[4-[2-(4-fluorophenyl)ethyl]piperazine-1-carbonyl]-1h-indole-3-carbonitrile Chemical compound C1=CC(F)=CC=C1CCN1CCN(C(=O)C=2C=C3NC=C(C3=CC=2)C#N)CC1 ZZDGTNIPZHMQHT-UHFFFAOYSA-N 0.000 claims description 2
- AUOYBIHZSREVMS-UHFFFAOYSA-N 7-[4-(2-naphthalen-2-ylethyl)piperazine-1-carbonyl]-1h-indole-3-carbonitrile Chemical compound C1CN(CCC=2C=C3C=CC=CC3=CC=2)CCN1C(=O)C1=CC=CC2=C1NC=C2C#N AUOYBIHZSREVMS-UHFFFAOYSA-N 0.000 claims description 2
- ZRXBCXGGXCXHCB-UHFFFAOYSA-N 7-[4-[2-(2,4-difluorophenyl)ethyl]piperazine-1-carbonyl]-1h-indole-3-carbonitrile Chemical compound FC1=CC(F)=CC=C1CCN1CCN(C(=O)C=2C=3NC=C(C=3C=CC=2)C#N)CC1 ZRXBCXGGXCXHCB-UHFFFAOYSA-N 0.000 claims description 2
- RISLQOLUWBPIBT-UHFFFAOYSA-N 7-[4-[2-(2-fluorophenyl)ethyl]piperazine-1-carbonyl]-1h-indole-3-carbonitrile Chemical compound FC1=CC=CC=C1CCN1CCN(C(=O)C=2C=3NC=C(C=3C=CC=2)C#N)CC1 RISLQOLUWBPIBT-UHFFFAOYSA-N 0.000 claims description 2
- URZXKENEGDHBHG-UHFFFAOYSA-N 7-[4-[2-(4-fluorophenyl)ethyl]piperazine-1-carbonyl]-1h-indole-3-carbaldehyde Chemical compound C1=CC(F)=CC=C1CCN1CCN(C(=O)C=2C=3NC=C(C=O)C=3C=CC=2)CC1 URZXKENEGDHBHG-UHFFFAOYSA-N 0.000 claims description 2
- SOONQGBOUDZOIC-UHFFFAOYSA-N 7-[4-[2-(4-fluorophenyl)ethyl]piperazine-1-carbonyl]-1h-indole-3-carboxamide Chemical compound C1=CC=C2C(C(=O)N)=CNC2=C1C(=O)N(CC1)CCN1CCC1=CC=C(F)C=C1 SOONQGBOUDZOIC-UHFFFAOYSA-N 0.000 claims description 2
- PRBFOWAWDTWTSF-UHFFFAOYSA-N 7-[4-[2-(5-chlorothiophen-2-yl)ethyl]piperazine-1-carbonyl]-1h-indole-3-carbonitrile Chemical compound S1C(Cl)=CC=C1CCN1CCN(C(=O)C=2C=3NC=C(C=3C=CC=2)C#N)CC1 PRBFOWAWDTWTSF-UHFFFAOYSA-N 0.000 claims description 2
- IXWJVFZAWRNDHS-UHFFFAOYSA-N [4-[2-(4-fluorophenyl)ethyl]piperazin-1-yl]-(1h-indol-4-yl)methanone Chemical compound C1=CC(F)=CC=C1CCN1CCN(C(=O)C=2C=3C=CNC=3C=CC=2)CC1 IXWJVFZAWRNDHS-UHFFFAOYSA-N 0.000 claims description 2
- GKUPWPKKZCZYFT-UHFFFAOYSA-N [4-[2-(4-fluorophenyl)ethyl]piperazin-1-yl]-(1h-indol-6-yl)methanone Chemical compound C1=CC(F)=CC=C1CCN1CCN(C(=O)C=2C=C3NC=CC3=CC=2)CC1 GKUPWPKKZCZYFT-UHFFFAOYSA-N 0.000 claims description 2
- TVSKQLKQIRBBHJ-UHFFFAOYSA-N [4-[2-(4-fluorophenyl)ethyl]piperazin-1-yl]-(1h-indol-7-yl)methanone Chemical compound C1=CC(F)=CC=C1CCN1CCN(C(=O)C=2C=3NC=CC=3C=CC=2)CC1 TVSKQLKQIRBBHJ-UHFFFAOYSA-N 0.000 claims description 2
- HSKNMSVMVMXGRH-UHFFFAOYSA-N [4-[2-(5-chlorothiophen-2-yl)ethyl]piperazin-1-yl]-(1h-indol-6-yl)methanone Chemical compound S1C(Cl)=CC=C1CCN1CCN(C(=O)C=2C=C3NC=CC3=CC=2)CC1 HSKNMSVMVMXGRH-UHFFFAOYSA-N 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 claims 3
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 44
- 238000002844 melting Methods 0.000 description 28
- 230000008018 melting Effects 0.000 description 28
- 239000003814 drug Substances 0.000 description 12
- 125000004432 carbon atom Chemical group C* 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical group C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- 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
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 125000002252 acyl group Chemical group 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
- 125000002947 alkylene group Chemical group 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 125000000623 heterocyclic group Chemical group 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 208000024827 Alzheimer disease Diseases 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 125000001041 indolyl group Chemical group 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 201000000980 schizophrenia Diseases 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- WOSOETCNFILDMJ-UHFFFAOYSA-N 1h-indol-5-yl-[4-(2-phenylethyl)piperazin-1-yl]methanone Chemical compound C=1C=C2NC=CC2=CC=1C(=O)N(CC1)CCN1CCC1=CC=CC=C1 WOSOETCNFILDMJ-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 208000032841 Bulimia Diseases 0.000 description 3
- 206010006550 Bulimia nervosa Diseases 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 208000030814 Eating disease Diseases 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 208000019454 Feeding and Eating disease Diseases 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 3
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 3
- 208000018737 Parkinson disease Diseases 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 208000028017 Psychotic disease Diseases 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000003708 ampul Substances 0.000 description 3
- 230000006399 behavior Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000002775 capsule Substances 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
- 208000035475 disorder Diseases 0.000 description 3
- 235000014632 disordered eating Nutrition 0.000 description 3
- 239000012154 double-distilled water Substances 0.000 description 3
- 230000002996 emotional effect Effects 0.000 description 3
- 125000002541 furyl group Chemical group 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- IUVCFHHAEHNCFT-INIZCTEOSA-N 2-[(1s)-1-[4-amino-3-(3-fluoro-4-propan-2-yloxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]ethyl]-6-fluoro-3-(3-fluorophenyl)chromen-4-one Chemical compound C1=C(F)C(OC(C)C)=CC=C1C(C1=C(N)N=CN=C11)=NN1[C@@H](C)C1=C(C=2C=C(F)C=CC=2)C(=O)C2=CC(F)=CC=C2O1 IUVCFHHAEHNCFT-INIZCTEOSA-N 0.000 description 2
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 2
- 208000000103 Anorexia Nervosa Diseases 0.000 description 2
- 208000019901 Anxiety disease Diseases 0.000 description 2
- 208000020706 Autistic disease Diseases 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- 208000012239 Developmental disease Diseases 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 208000023105 Huntington disease Diseases 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 208000019695 Migraine disease Diseases 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 208000012902 Nervous system disease Diseases 0.000 description 2
- 208000025966 Neurological disease Diseases 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 206010036618 Premenstrual syndrome Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-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
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- ZJBYTFKPIHNUHE-UHFFFAOYSA-N [4-[2-(5-chlorothiophen-2-yl)ethyl]piperazin-1-yl]-(1h-indol-4-yl)methanone Chemical compound S1C(Cl)=CC=C1CCN1CCN(C(=O)C=2C=3C=CNC=3C=CC=2)CC1 ZJBYTFKPIHNUHE-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
- 208000022531 anorexia Diseases 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 206010008118 cerebral infarction Diseases 0.000 description 2
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 206010061428 decreased appetite Diseases 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 206010027175 memory impairment Diseases 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 206010027599 migraine Diseases 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 235000019271 petrolatum Nutrition 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 235000011007 phosphoric acid Nutrition 0.000 description 2
- WLJVNTCWHIRURA-UHFFFAOYSA-N pimelic acid Chemical compound OC(=O)CCCCCC(O)=O WLJVNTCWHIRURA-UHFFFAOYSA-N 0.000 description 2
- 150000004885 piperazines Chemical class 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- GYYZMAFTPQTGSX-UHFFFAOYSA-N (2,3-dimethyl-1h-indol-7-yl)-[4-(2-phenylethyl)piperazin-1-yl]methanone Chemical compound C1=CC=C2C(C)=C(C)NC2=C1C(=O)N(CC1)CCN1CCC1=CC=CC=C1 GYYZMAFTPQTGSX-UHFFFAOYSA-N 0.000 description 1
- FUGBUICYOXJWRI-UHFFFAOYSA-N (2,3-dimethyl-1h-indol-7-yl)-[4-(2-thiophen-2-ylethyl)piperazin-1-yl]methanone Chemical compound C1=CC=C2C(C)=C(C)NC2=C1C(=O)N(CC1)CCN1CCC1=CC=CS1 FUGBUICYOXJWRI-UHFFFAOYSA-N 0.000 description 1
- BOJWPKRTMICCQN-UHFFFAOYSA-N (2,3-dimethyl-1h-indol-7-yl)-[4-(2-thiophen-3-ylethyl)piperazin-1-yl]methanone Chemical compound C1=CC=C2C(C)=C(C)NC2=C1C(=O)N(CC1)CCN1CCC=1C=CSC=1 BOJWPKRTMICCQN-UHFFFAOYSA-N 0.000 description 1
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- 125000005919 1,2,2-trimethylpropyl group Chemical group 0.000 description 1
- LKUAPSRIYZLAAO-UHFFFAOYSA-N 1-(2-phenylethyl)piperazine Chemical compound C1CNCCN1CCC1=CC=CC=C1 LKUAPSRIYZLAAO-UHFFFAOYSA-N 0.000 description 1
- HLWLAWDUWNRGOF-UHFFFAOYSA-N 1-[2-(4-fluorophenyl)ethyl]-4-(1h-indole-6-carbonyl)piperazine-2-carbaldehyde Chemical compound C1=CC(F)=CC=C1CCN1C(C=O)CN(C(=O)C=2C=C3NC=CC3=CC=2)CC1 HLWLAWDUWNRGOF-UHFFFAOYSA-N 0.000 description 1
- 125000006218 1-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006219 1-ethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 1
- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 1
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
- BPVFKPUPOSRPPI-UHFFFAOYSA-N 1h-indol-4-yl-[4-(2-thiophen-2-ylethyl)piperazin-1-yl]methanone Chemical compound C=1C=CC=2NC=CC=2C=1C(=O)N(CC1)CCN1CCC1=CC=CS1 BPVFKPUPOSRPPI-UHFFFAOYSA-N 0.000 description 1
- SGCYSHURTIOGSZ-UHFFFAOYSA-N 1h-indol-4-yl-[4-(2-thiophen-3-ylethyl)piperazin-1-yl]methanone Chemical compound C=1C=CC=2NC=CC=2C=1C(=O)N(CC1)CCN1CCC=1C=CSC=1 SGCYSHURTIOGSZ-UHFFFAOYSA-N 0.000 description 1
- UONDKJUCXIYJMR-UHFFFAOYSA-N 1h-indol-5-yl-[4-(2-thiophen-2-ylethyl)piperazin-1-yl]methanone Chemical compound C=1C=C2NC=CC2=CC=1C(=O)N(CC1)CCN1CCC1=CC=CS1 UONDKJUCXIYJMR-UHFFFAOYSA-N 0.000 description 1
- KCNGMWFKCDWPAR-UHFFFAOYSA-N 1h-indol-5-yl-[4-(2-thiophen-3-ylethyl)piperazin-1-yl]methanone Chemical compound C=1C=C2NC=CC2=CC=1C(=O)N(CC1)CCN1CCC=1C=CSC=1 KCNGMWFKCDWPAR-UHFFFAOYSA-N 0.000 description 1
- RZNZQLGCNBDVCR-UHFFFAOYSA-N 1h-indol-6-yl-[4-(2-phenylethyl)piperazin-1-yl]methanone Chemical compound C=1C=C2C=CNC2=CC=1C(=O)N(CC1)CCN1CCC1=CC=CC=C1 RZNZQLGCNBDVCR-UHFFFAOYSA-N 0.000 description 1
- SFAVAAQSVUQWCB-UHFFFAOYSA-N 1h-indol-6-yl-[4-(2-thiophen-3-ylethyl)piperazin-1-yl]methanone Chemical compound C=1C=C2C=CNC2=CC=1C(=O)N(CC1)CCN1CCC=1C=CSC=1 SFAVAAQSVUQWCB-UHFFFAOYSA-N 0.000 description 1
- LOPYOIFYEDBOJN-UHFFFAOYSA-N 1h-indol-7-yl-[4-(2-phenylethyl)piperazin-1-yl]methanone Chemical compound C=1C=CC=2C=CNC=2C=1C(=O)N(CC1)CCN1CCC1=CC=CC=C1 LOPYOIFYEDBOJN-UHFFFAOYSA-N 0.000 description 1
- NSUMZNDMYIZBCK-UHFFFAOYSA-N 1h-indol-7-yl-[4-(2-thiophen-2-ylethyl)piperazin-1-yl]methanone Chemical compound C=1C=CC=2C=CNC=2C=1C(=O)N(CC1)CCN1CCC1=CC=CS1 NSUMZNDMYIZBCK-UHFFFAOYSA-N 0.000 description 1
- DPDHPENZMDCVQZ-UHFFFAOYSA-N 1h-indol-7-yl-[4-(2-thiophen-3-ylethyl)piperazin-1-yl]methanone Chemical compound C=1C=CC=2C=CNC=2C=1C(=O)N(CC1)CCN1CCC=1C=CSC=1 DPDHPENZMDCVQZ-UHFFFAOYSA-N 0.000 description 1
- ROGHUJUFCRFUSO-UHFFFAOYSA-N 1h-indole-4-carboxylic acid Chemical compound OC(=O)C1=CC=CC2=C1C=CN2 ROGHUJUFCRFUSO-UHFFFAOYSA-N 0.000 description 1
- OXQGTIUCKGYOAA-UHFFFAOYSA-N 2-Ethylbutanoic acid Chemical compound CCC(CC)C(O)=O OXQGTIUCKGYOAA-UHFFFAOYSA-N 0.000 description 1
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 1
- ABFPKTQEQNICFT-UHFFFAOYSA-M 2-chloro-1-methylpyridin-1-ium;iodide Chemical compound [I-].C[N+]1=CC=CC=C1Cl ABFPKTQEQNICFT-UHFFFAOYSA-M 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- 125000005916 2-methylpentyl group Chemical group 0.000 description 1
- KLLLJCACIRKBDT-UHFFFAOYSA-N 2-phenyl-1H-indole Chemical class N1C2=CC=CC=C2C=C1C1=CC=CC=C1 KLLLJCACIRKBDT-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000004362 3,4,5-trichlorophenyl group Chemical group [H]C1=C(Cl)C(Cl)=C(Cl)C([H])=C1* 0.000 description 1
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 1
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 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
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 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
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical compound [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
- 125000004539 5-benzimidazolyl group Chemical group N1=CNC2=C1C=CC(=C2)* 0.000 description 1
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
- BCJRIVVOPACMOF-UHFFFAOYSA-N 6,7,8,9-tetrahydro-5h-carbazol-3-yl-[4-(2-thiophen-2-ylethyl)piperazin-1-yl]methanone Chemical compound C=1C=C2NC=3CCCCC=3C2=CC=1C(=O)N(CC1)CCN1CCC1=CC=CS1 BCJRIVVOPACMOF-UHFFFAOYSA-N 0.000 description 1
- GIELGMSZIUMTSX-UHFFFAOYSA-N 6,7,8,9-tetrahydro-5h-carbazol-3-yl-[4-(2-thiophen-3-ylethyl)piperazin-1-yl]methanone Chemical compound C=1C=C2NC=3CCCCC=3C2=CC=1C(=O)N(CC1)CCN1CCC=1C=CSC=1 GIELGMSZIUMTSX-UHFFFAOYSA-N 0.000 description 1
- FXPKYFQOGJFNOP-UHFFFAOYSA-N 7-[4-(2-phenylethyl)piperazine-1-carbonyl]-1h-indole-3-carbonitrile Chemical compound C=1C=CC=2C(C#N)=CNC=2C=1C(=O)N(CC1)CCN1CCC1=CC=CC=C1 FXPKYFQOGJFNOP-UHFFFAOYSA-N 0.000 description 1
- LXARYHPHGDJDAG-UHFFFAOYSA-N 7-[4-[2-(4-fluorophenyl)ethyl]piperazine-1-carbonyl]-1h-indole-2,3-dione Chemical compound C1=CC(F)=CC=C1CCN1CCN(C(=O)C=2C=3NC(=O)C(=O)C=3C=CC=2)CC1 LXARYHPHGDJDAG-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 208000008811 Agoraphobia Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 206010003225 Arteriospasm coronary Diseases 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- 208000036640 Asperger disease Diseases 0.000 description 1
- 201000006062 Asperger syndrome Diseases 0.000 description 1
- 206010003805 Autism Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 206010008531 Chills Diseases 0.000 description 1
- 208000003890 Coronary Vasospasm Diseases 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010013654 Drug abuse Diseases 0.000 description 1
- 208000012661 Dyskinesia Diseases 0.000 description 1
- 208000014094 Dystonic disease Diseases 0.000 description 1
- 208000017701 Endocrine disease Diseases 0.000 description 1
- BGHDUTQZGWOQIA-VQSKNWBGSA-N Ergovaline Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)C(C)C)C)C2)=C3C2=CNC3=C1 BGHDUTQZGWOQIA-VQSKNWBGSA-N 0.000 description 1
- 208000027776 Extrapyramidal disease Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 208000008454 Hyperhidrosis Diseases 0.000 description 1
- 206010020740 Hyperproteinaemia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000020358 Learning disease Diseases 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 206010028289 Muscle atrophy Diseases 0.000 description 1
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 1
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 239000008896 Opium Substances 0.000 description 1
- 206010033664 Panic attack Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 201000001880 Sexual dysfunction Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 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
- 229920002472 Starch Polymers 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 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
- 208000001871 Tachycardia Diseases 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 208000006906 Vascular Ring Diseases 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- 206010047163 Vasospasm Diseases 0.000 description 1
- LJHGXVATEQMJSX-UHFFFAOYSA-N [4-(2-phenylethyl)piperazin-1-yl]-(6,7,8,9-tetrahydro-5h-carbazol-3-yl)methanone Chemical compound C=1C=C2NC=3CCCCC=3C2=CC=1C(=O)N(CC1)CCN1CCC1=CC=CC=C1 LJHGXVATEQMJSX-UHFFFAOYSA-N 0.000 description 1
- FOVICFIAZDFOQR-UHFFFAOYSA-N [4-[2-(2,5-dichlorothiophen-3-yl)ethyl]piperazin-1-yl]-(1h-indol-4-yl)methanone Chemical compound S1C(Cl)=CC(CCN2CCN(CC2)C(=O)C=2C=3C=CNC=3C=CC=2)=C1Cl FOVICFIAZDFOQR-UHFFFAOYSA-N 0.000 description 1
- UQGHRKLAGLIVDG-UHFFFAOYSA-N [4-[2-(2,5-dichlorothiophen-3-yl)ethyl]piperazin-1-yl]-(1h-indol-5-yl)methanone Chemical compound S1C(Cl)=CC(CCN2CCN(CC2)C(=O)C=2C=C3C=CNC3=CC=2)=C1Cl UQGHRKLAGLIVDG-UHFFFAOYSA-N 0.000 description 1
- CYCXVEHUGQCALV-UHFFFAOYSA-N [4-[2-(2,5-dichlorothiophen-3-yl)ethyl]piperazin-1-yl]-(1h-indol-6-yl)methanone Chemical compound S1C(Cl)=CC(CCN2CCN(CC2)C(=O)C=2C=C3NC=CC3=CC=2)=C1Cl CYCXVEHUGQCALV-UHFFFAOYSA-N 0.000 description 1
- KJNIKXFACLZCIL-UHFFFAOYSA-N [4-[2-(2,5-dichlorothiophen-3-yl)ethyl]piperazin-1-yl]-(1h-indol-7-yl)methanone Chemical compound S1C(Cl)=CC(CCN2CCN(CC2)C(=O)C=2C=3NC=CC=3C=CC=2)=C1Cl KJNIKXFACLZCIL-UHFFFAOYSA-N 0.000 description 1
- PSCNTCPDGCNHBI-UHFFFAOYSA-N [4-[2-(2,5-dichlorothiophen-3-yl)ethyl]piperazin-1-yl]-(2,3-dimethyl-1h-indol-7-yl)methanone Chemical compound C1=CC=C2C(C)=C(C)NC2=C1C(=O)N(CC1)CCN1CCC=1C=C(Cl)SC=1Cl PSCNTCPDGCNHBI-UHFFFAOYSA-N 0.000 description 1
- MHEMKQQXSVCAKW-UHFFFAOYSA-N [4-[2-(2,5-dichlorothiophen-3-yl)ethyl]piperazin-1-yl]-(6,7,8,9-tetrahydro-5h-carbazol-3-yl)methanone Chemical compound S1C(Cl)=CC(CCN2CCN(CC2)C(=O)C=2C=C3C=4CCCCC=4NC3=CC=2)=C1Cl MHEMKQQXSVCAKW-UHFFFAOYSA-N 0.000 description 1
- BGHWYAZAALIVLU-UHFFFAOYSA-N [4-[2-(4-fluorophenyl)ethyl]piperazin-1-yl]-(1h-indol-5-yl)methanone Chemical compound C1=CC(F)=CC=C1CCN1CCN(C(=O)C=2C=C3C=CNC3=CC=2)CC1 BGHWYAZAALIVLU-UHFFFAOYSA-N 0.000 description 1
- QCDBLMOASSURQI-UHFFFAOYSA-N [4-[2-(4-fluorophenyl)ethyl]piperazin-1-yl]-(6,7,8,9-tetrahydro-5h-carbazol-3-yl)methanone Chemical compound C1=CC(F)=CC=C1CCN1CCN(C(=O)C=2C=C3C=4CCCCC=4NC3=CC=2)CC1 QCDBLMOASSURQI-UHFFFAOYSA-N 0.000 description 1
- ABXMJVXMTYEIEE-UHFFFAOYSA-N [4-[2-(5-chlorothiophen-2-yl)ethyl]piperazin-1-yl]-(1h-indol-5-yl)methanone Chemical compound S1C(Cl)=CC=C1CCN1CCN(C(=O)C=2C=C3C=CNC3=CC=2)CC1 ABXMJVXMTYEIEE-UHFFFAOYSA-N 0.000 description 1
- METQSVDRQWPQMI-UHFFFAOYSA-N [4-[2-(5-chlorothiophen-2-yl)ethyl]piperazin-1-yl]-(1h-indol-7-yl)methanone Chemical compound S1C(Cl)=CC=C1CCN1CCN(C(=O)C=2C=3NC=CC=3C=CC=2)CC1 METQSVDRQWPQMI-UHFFFAOYSA-N 0.000 description 1
- BPKCBDVLSGYTNM-UHFFFAOYSA-N [4-[2-(5-chlorothiophen-2-yl)ethyl]piperazin-1-yl]-(2,3-dimethyl-1h-indol-7-yl)methanone Chemical compound C1=CC=C2C(C)=C(C)NC2=C1C(=O)N(CC1)CCN1CCC1=CC=C(Cl)S1 BPKCBDVLSGYTNM-UHFFFAOYSA-N 0.000 description 1
- GBQVTJMIVAZXNN-UHFFFAOYSA-N [4-[2-(5-chlorothiophen-2-yl)ethyl]piperazin-1-yl]-(6,7,8,9-tetrahydro-5h-carbazol-3-yl)methanone Chemical compound S1C(Cl)=CC=C1CCN1CCN(C(=O)C=2C=C3C=4CCCCC=4NC3=CC=2)CC1 GBQVTJMIVAZXNN-UHFFFAOYSA-N 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229940025084 amphetamine Drugs 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000003288 anthiarrhythmic effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 239000000164 antipsychotic agent Substances 0.000 description 1
- 229940005529 antipsychotics Drugs 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 230000000949 anxiolytic effect Effects 0.000 description 1
- 229940005530 anxiolytics Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000005279 aryl sulfonyloxy group Chemical group 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
- 239000000305 astragalus gummifer gum Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 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
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 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
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229960003920 cocaine Drugs 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 201000011634 coronary artery vasospasm Diseases 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 229940043264 dodecyl sulfate Drugs 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 208000010118 dystonia Diseases 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- BGHDUTQZGWOQIA-RKUMIMICSA-N ergovaline Natural products O=C(N[C@@]1(C)C(=O)N2[C@H](C(C)C)C(=O)N3[C@@H]([C@]2(O)O1)CCC3)[C@@H]1C=C2[C@H](N(C)C1)Cc1c3c([nH]c1)cccc23 BGHDUTQZGWOQIA-RKUMIMICSA-N 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 206010016629 fibroma Diseases 0.000 description 1
- 208000020336 fibromyxoid tumor Diseases 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- WTDFFADXONGQOM-UHFFFAOYSA-N formaldehyde;hydrochloride Chemical compound Cl.O=C WTDFFADXONGQOM-UHFFFAOYSA-N 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 210000005153 frontal cortex Anatomy 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 229950006191 gluconic acid Drugs 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000036541 health Effects 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
- 150000004677 hydrates Chemical class 0.000 description 1
- YPGCWEMNNLXISK-UHFFFAOYSA-N hydratropic acid Chemical compound OC(=O)C(C)C1=CC=CC=C1 YPGCWEMNNLXISK-UHFFFAOYSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 239000011147 inorganic material Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000004410 intraocular pressure Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 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
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 201000010901 lateral sclerosis Diseases 0.000 description 1
- 201000003723 learning disability Diseases 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
- CKJNUZNMWOVDFN-UHFFFAOYSA-N methanone Chemical compound O=[CH-] CKJNUZNMWOVDFN-UHFFFAOYSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 208000005264 motor neuron disease Diseases 0.000 description 1
- 230000020763 muscle atrophy Effects 0.000 description 1
- 201000000585 muscular atrophy Diseases 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- 229920002113 octoxynol Polymers 0.000 description 1
- 229960001027 opium Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 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
- 208000019906 panic disease Diseases 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003368 psychostimulant agent Substances 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- BKXVVCILCIUCLG-UHFFFAOYSA-N raloxifene hydrochloride Chemical compound [H+].[Cl-].C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 BKXVVCILCIUCLG-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 231100000872 sexual dysfunction Toxicity 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 201000002859 sleep apnea Diseases 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 239000003381 stabilizer Substances 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
- 208000011117 substance-related disease Diseases 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 230000035900 sweating Effects 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000002885 thrombogenetic effect Effects 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 125000004784 trichloromethoxy group Chemical group ClC(O*)(Cl)Cl 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Diabetes (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pain & Pain Management (AREA)
- Psychology (AREA)
- Endocrinology (AREA)
- Hospice & Palliative Care (AREA)
- Obesity (AREA)
- Nutrition Science (AREA)
- Hematology (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19934433A DE19934433A1 (de) | 1999-07-22 | 1999-07-22 | N-(Indolcarbonyl-)piperazinderivate |
| DE19934433.7 | 1999-07-22 | ||
| PCT/EP2000/006464 WO2001007435A2 (de) | 1999-07-22 | 2000-07-07 | N-(indolcarbonyl-)piperazinderivate als 5-ht2a-rezeptor liganden |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2011166851A Division JP2012006940A (ja) | 1999-07-22 | 2011-07-29 | Ｎ−（インドールカルボニル）ピペラジン誘導体 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2003505458A JP2003505458A (ja) | 2003-02-12 |
| JP2003505458A5 JP2003505458A5 (enExample) | 2011-04-14 |
| JP5242871B2 true JP5242871B2 (ja) | 2013-07-24 |
Family
ID=7915702
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001512519A Expired - Fee Related JP5242871B2 (ja) | 1999-07-22 | 2000-07-07 | Ｎ−（インドールカルボニル）ピペラジン誘導体 |
| JP2011166851A Pending JP2012006940A (ja) | 1999-07-22 | 2011-07-29 | Ｎ−（インドールカルボニル）ピペラジン誘導体 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2011166851A Pending JP2012006940A (ja) | 1999-07-22 | 2011-07-29 | Ｎ−（インドールカルボニル）ピペラジン誘導体 |
Country Status (26)
| Country | Link |
|---|---|
| US (2) | US6838461B1 (enExample) |
| EP (1) | EP1198453B9 (enExample) |
| JP (2) | JP5242871B2 (enExample) |
| KR (1) | KR100779207B1 (enExample) |
| CN (1) | CN1229345C (enExample) |
| AR (1) | AR024819A1 (enExample) |
| AT (1) | ATE236877T1 (enExample) |
| AU (1) | AU770411B2 (enExample) |
| BR (1) | BR0012607A (enExample) |
| CA (1) | CA2383779C (enExample) |
| CZ (1) | CZ300510B6 (enExample) |
| DE (2) | DE19934433A1 (enExample) |
| DK (1) | DK1198453T5 (enExample) |
| ES (1) | ES2192535T3 (enExample) |
| HK (1) | HK1048636B (enExample) |
| HU (1) | HUP0201988A3 (enExample) |
| MX (1) | MXPA02000730A (enExample) |
| MY (1) | MY122531A (enExample) |
| NO (1) | NO322154B1 (enExample) |
| PL (1) | PL201893B1 (enExample) |
| PT (1) | PT1198453E (enExample) |
| RU (1) | RU2251548C2 (enExample) |
| SK (1) | SK286066B6 (enExample) |
| UA (1) | UA73518C2 (enExample) |
| WO (1) | WO2001007435A2 (enExample) |
| ZA (1) | ZA200201486B (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012006940A (ja) * | 1999-07-22 | 2012-01-12 | Merck Patent Gmbh | Ｎ−（インドールカルボニル）ピペラジン誘導体 |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6589954B1 (en) | 1998-05-22 | 2003-07-08 | Scios, Inc. | Compounds and methods to treat cardiac failure and other disorders |
| IL146309A (en) | 1999-05-21 | 2008-03-20 | Scios Inc | Derivatives of the indole type and pharmaceutical preparations containing them as inhibitors of kinase p38 |
| DE19934432A1 (de) * | 1999-07-22 | 2001-02-01 | Merck Patent Gmbh | Indolderivate |
| US20020095134A1 (en) * | 1999-10-14 | 2002-07-18 | Pettis Ronald J. | Method for altering drug pharmacokinetics based on medical delivery platform |
| US8465468B1 (en) | 2000-06-29 | 2013-06-18 | Becton, Dickinson And Company | Intradermal delivery of substances |
| US20020156453A1 (en) * | 1999-10-14 | 2002-10-24 | Pettis Ronald J. | Method and device for reducing therapeutic dosage |
| DE10102053A1 (de) * | 2001-01-17 | 2002-07-18 | Merck Patent Gmbh | Piperazinylcarbonylchinoline und -isochinoline |
| ATE331707T1 (de) * | 2001-06-15 | 2006-07-15 | Hoffmann La Roche | 4 piperazinylindolderivate mit affinität zum 5- ht6-rezeptor |
| WO2003002069A2 (en) * | 2001-06-29 | 2003-01-09 | Becton, Dickinson And Company | Intradermal delivery of vaccines and gene therapeutic agents via microcannula |
| DE10157673A1 (de) * | 2001-11-24 | 2003-06-05 | Merck Patent Gmbh | Verwendung von N-(Indolcarbonyl-)piperazinderivaten |
| GB0203811D0 (en) | 2002-02-18 | 2002-04-03 | Glaxo Group Ltd | Compounds |
| DE10212564B4 (de) * | 2002-03-12 | 2007-04-19 | Neurobiotec Gmbh | 1-Allyl-ergotalkaloid-Derivate und ihre Verwendung zur Prophylaxe und Therapie von Migräne |
| DE10217006A1 (de) * | 2002-04-16 | 2003-11-06 | Merck Patent Gmbh | Substituierte Indole |
| BR0313890A (pt) * | 2002-08-30 | 2005-07-26 | Becton Dickinson Co | Método de controle da farmacocinética de compostos imunomoduladores |
| DE10246357A1 (de) * | 2002-10-04 | 2004-04-15 | Merck Patent Gmbh | Verwendung von 5-HT2Rezeptorantagonisten |
| US20050163711A1 (en) * | 2003-06-13 | 2005-07-28 | Becton, Dickinson And Company, Inc. | Intra-dermal delivery of biologically active agents |
| EP1658078A4 (en) * | 2003-08-26 | 2009-05-06 | Becton Dickinson Co | PROCESS FOR THE INTRADERMAL DISTRIBUTION OF THERAPEUTIC AGENTS |
| US20050256499A1 (en) * | 2004-03-03 | 2005-11-17 | Pettis Ronald J | Methods and devices for improving delivery of a substance to skin |
| CA2564068A1 (en) * | 2004-04-15 | 2005-11-17 | Samaritan Pharmaceuticals, Inc. | Use of (4-alkylpiperazinyl) (phenyl) methanones in the treatment of alzheimer's disease |
| WO2005115360A2 (en) * | 2004-05-11 | 2005-12-08 | Becton, Dickinson And Company | Formulations of anti-pain agents and methods of using the same |
| DE102004047517A1 (de) * | 2004-09-28 | 2006-03-30 | Merck Patent Gmbh | Neuartige Kristallform von (3-Cyan-1H-indol-7-yl)-[4-(4-fluorphenethyl)-piperazin-1-yl]-methanon, Hydrochlorid |
| PT1831159E (pt) * | 2004-12-21 | 2010-03-03 | Hoffmann La Roche | Derivados de tetralina e de indano e as suas utilizações |
| GT200600042A (es) * | 2005-02-10 | 2006-09-27 | Aventis Pharma Inc | Compuestos de bis arilo y heteroarilo sustituido como antagonistas selectivos de 5ht2a |
| BRPI0711556A2 (pt) | 2006-05-05 | 2011-11-08 | Merck Patent Gmbh | fosfato de (3-ciano-1h-indol-7-il)-[4-(4-fluorofenetil)piperazin-1-i l]metanona cristalina |
| US7514433B2 (en) * | 2006-08-03 | 2009-04-07 | Hoffmann-La Roche Inc. | 1H-indole-6-yl-piperazin-1-yl-methanone derivatives |
| PL2155736T3 (pl) * | 2007-05-14 | 2012-09-28 | Sk Biopharmaceuticals Co Ltd | Nowy związek, karbamoiloksyaryloalkanoiloarylopiperazyna, kompozycje farmaceutyczne zawierające ten związek oraz sposoby leczenia bólu, stanu lękowego i depresji przez podawanie tego związku |
| EP2008656A1 (en) * | 2007-06-28 | 2008-12-31 | Bergen Teknologioverforing AS | Compositions for the treatment of hyperphenylalaninemia |
| EP2190844B3 (en) * | 2007-08-15 | 2013-07-17 | Arena Pharmaceuticals, Inc. | Imidazo[1,2-a]pyridine derivatives as modulators of the 5-ht2a serotonin receptor useful for the treatment of disorders related thereto |
| KR101062376B1 (ko) | 2008-04-10 | 2011-09-06 | 한국화학연구원 | 신규 인돌 카르복실산 비스피리딜 카르복사마이드 유도체,이의 제조방법 및 이를 유효성분으로 함유하는 조성물 |
| US9308323B2 (en) | 2011-11-15 | 2016-04-12 | Smiths Medical Asd, Inc. | Systems and methods for illuminated medical tubing detection and management indicating a characteristic of at least one infusion pump |
| RU2549963C1 (ru) * | 2014-04-08 | 2015-05-10 | Государственное бюджетное образовательное учреждение высшего профессионального образования "Дальневосточный государственный медицинский университет" Министерства здравоохранения Российской Федерации (ГБОУ ВПО "ДВГМУ" Минздрава России) | Способ прогнозирования развития критической печеночной недостаточности на основании сывороточного уровня селена |
| ES2879351T3 (es) | 2016-02-25 | 2021-11-22 | Asceneuron Sa | Sales de derivados de piperazina obtenidas por adición de ácidos |
| GB2554371B (en) * | 2016-09-22 | 2019-10-09 | Resolute Energy Solutions Ltd | Well apparatus and associated methods |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU630334B2 (en) | 1987-09-24 | 1992-10-29 | Jencap Research Ltd. | Hormone preparations for hormone replacement therapy and contraceptive method |
| US5093341A (en) * | 1987-12-17 | 1992-03-03 | Merrell Dow Pharmaceuticals Inc. | N-aralkyl piperidine derivatives useful as antithrombolytic agents |
| US5032604A (en) * | 1989-12-08 | 1991-07-16 | Merck & Co., Inc. | Class III antiarrhythmic agents |
| US5032598A (en) | 1989-12-08 | 1991-07-16 | Merck & Co., Inc. | Nitrogens containing heterocyclic compounds as class III antiarrhythmic agents |
| US5330986A (en) * | 1992-11-24 | 1994-07-19 | Hoechst-Roussel Pharmaceuticals Inc. | Indole-7-carboxamide derivatives |
| ZA954689B (en) | 1994-06-08 | 1996-01-29 | Lundbeck & Co As H | 4-Aryl-1-(indanmethyl dihydrobenzofuranmethyl or dihydrobenzothiophenemethyl) piperidines tetrahydropyridines or piperazines |
| WO1998006715A1 (en) | 1996-08-09 | 1998-02-19 | Smithkline Beecham Corporation | Novel piperazine containing compounds |
| GB9718712D0 (en) | 1997-09-03 | 1997-11-12 | Merck Sharp & Dohme | Theraputic Agents |
| DE19934432A1 (de) * | 1999-07-22 | 2001-02-01 | Merck Patent Gmbh | Indolderivate |
| DE19934433A1 (de) * | 1999-07-22 | 2001-01-25 | Merck Patent Gmbh | N-(Indolcarbonyl-)piperazinderivate |
| CN1939045A (zh) * | 2004-04-07 | 2007-03-28 | 松下电器产业株式会社 | 信息交换支持装置和方法、以及信息交换支持程序 |
-
1999
- 1999-07-22 DE DE19934433A patent/DE19934433A1/de not_active Withdrawn
-
2000
- 2000-07-07 MX MXPA02000730A patent/MXPA02000730A/es active IP Right Grant
- 2000-07-07 ES ES00949288T patent/ES2192535T3/es not_active Expired - Lifetime
- 2000-07-07 PT PT00949288T patent/PT1198453E/pt unknown
- 2000-07-07 KR KR1020027000315A patent/KR100779207B1/ko not_active Expired - Fee Related
- 2000-07-07 PL PL353446A patent/PL201893B1/pl not_active IP Right Cessation
- 2000-07-07 CZ CZ20020068A patent/CZ300510B6/cs not_active IP Right Cessation
- 2000-07-07 HU HU0201988A patent/HUP0201988A3/hu unknown
- 2000-07-07 DE DE50001729T patent/DE50001729D1/de not_active Expired - Lifetime
- 2000-07-07 AT AT00949288T patent/ATE236877T1/de not_active IP Right Cessation
- 2000-07-07 SK SK51-2002A patent/SK286066B6/sk not_active IP Right Cessation
- 2000-07-07 CA CA2383779A patent/CA2383779C/en not_active Expired - Fee Related
- 2000-07-07 JP JP2001512519A patent/JP5242871B2/ja not_active Expired - Fee Related
- 2000-07-07 RU RU2002103302/04A patent/RU2251548C2/ru not_active IP Right Cessation
- 2000-07-07 AU AU62704/00A patent/AU770411B2/en not_active Ceased
- 2000-07-07 CN CNB00810719XA patent/CN1229345C/zh not_active Expired - Fee Related
- 2000-07-07 HK HK03100811.4A patent/HK1048636B/zh not_active IP Right Cessation
- 2000-07-07 BR BR0012607-1A patent/BR0012607A/pt active Search and Examination
- 2000-07-07 EP EP00949288A patent/EP1198453B9/de not_active Expired - Lifetime
- 2000-07-07 DK DK00949288T patent/DK1198453T5/da active
- 2000-07-07 WO PCT/EP2000/006464 patent/WO2001007435A2/de not_active Ceased
- 2000-07-07 US US10/031,367 patent/US6838461B1/en not_active Expired - Lifetime
- 2000-07-07 UA UA2002021354A patent/UA73518C2/uk unknown
- 2000-07-20 MY MYPI20003320A patent/MY122531A/en unknown
- 2000-07-21 AR ARP000103775A patent/AR024819A1/es active IP Right Grant
-
2002
- 2002-01-21 NO NO20020307A patent/NO322154B1/no not_active IP Right Cessation
- 2002-02-21 ZA ZA200201486A patent/ZA200201486B/en unknown
-
2004
- 2004-12-17 US US11/013,908 patent/US7084143B2/en not_active Expired - Fee Related
-
2011
- 2011-07-29 JP JP2011166851A patent/JP2012006940A/ja active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012006940A (ja) * | 1999-07-22 | 2012-01-12 | Merck Patent Gmbh | Ｎ−（インドールカルボニル）ピペラジン誘導体 |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5242871B2 (ja) | Ｎ−（インドールカルボニル）ピペラジン誘導体 | |
| KR100756506B1 (ko) | 인돌 유도체 | |
| JP4417624B2 (ja) | ピペラジニルカルボニルキノリンおよびイソキノリン | |
| KR20010112231A (ko) | ５―ｈｔ 재흡수 저해제 및 ５―ｈｔ１ｂ／１ｄ리간드로서의 아미드 및 우레아 유도체 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20070706 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20100824 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20101124 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20101201 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20101224 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20110106 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20110124 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20110131 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110224 |
|
| A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20110224 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20110329 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110729 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20110922 |
|
| RD13 | Notification of appointment of power of sub attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7433 Effective date: 20111011 |
|
| A912 | Re-examination (zenchi) completed and case transferred to appeal board |
Free format text: JAPANESE INTERMEDIATE CODE: A912 Effective date: 20111021 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20111012 |
|
| RD15 | Notification of revocation of power of sub attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7435 Effective date: 20120119 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130204 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20130404 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20160412 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |