HRP980441A2 - 2-(4-aryl or heteroaryl-piperazin-1-ylmethyl)-1h-indole derivatives - Google Patents
2-(4-aryl or heteroaryl-piperazin-1-ylmethyl)-1h-indole derivativesInfo
- Publication number
- HRP980441A2 HRP980441A2 HR60/055,764A HRP980441A HRP980441A2 HR P980441 A2 HRP980441 A2 HR P980441A2 HR P980441 A HRP980441 A HR P980441A HR P980441 A2 HRP980441 A2 HR P980441A2
- Authority
- HR
- Croatia
- Prior art keywords
- fluoro
- diseases
- piperazin
- hydrogen
- ylmethyl
- Prior art date
Links
- 229940054051 antipsychotic indole derivative Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 62
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 34
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
- 239000001257 hydrogen Substances 0.000 claims description 27
- 201000010099 disease Diseases 0.000 claims description 26
- 125000001153 fluoro group Chemical group F* 0.000 claims description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 19
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 18
- 241000124008 Mammalia Species 0.000 claims description 18
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 17
- 229960003638 dopamine Drugs 0.000 claims description 17
- 239000000126 substance Substances 0.000 claims description 16
- 201000009032 substance abuse Diseases 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- 208000020016 psychiatric disease Diseases 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 150000002431 hydrogen Chemical class 0.000 claims description 11
- 101150043870 Drd4 gene Proteins 0.000 claims description 10
- 125000001246 bromo group Chemical group Br* 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 9
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 9
- 208000016285 Movement disease Diseases 0.000 claims description 9
- 208000011117 substance-related disease Diseases 0.000 claims description 9
- 230000002792 vascular Effects 0.000 claims description 9
- 208000019553 vascular disease Diseases 0.000 claims description 9
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 8
- 206010012335 Dependence Diseases 0.000 claims description 8
- 230000000694 effects Effects 0.000 claims description 8
- 208000030533 eye disease Diseases 0.000 claims description 8
- 231100000736 substance abuse Toxicity 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 208000018737 Parkinson disease Diseases 0.000 claims description 7
- 239000003136 dopamine receptor stimulating agent Substances 0.000 claims description 7
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 7
- 206010047700 Vomiting Diseases 0.000 claims description 6
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 5
- 206010019280 Heart failures Diseases 0.000 claims description 5
- 208000023105 Huntington disease Diseases 0.000 claims description 5
- 206010020772 Hypertension Diseases 0.000 claims description 5
- 201000005625 Neuroleptic malignant syndrome Diseases 0.000 claims description 5
- 206010043118 Tardive Dyskinesia Diseases 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 201000000980 schizophrenia Diseases 0.000 claims description 5
- YXEZZMBABNHVFB-UHFFFAOYSA-N 5-fluoro-2-[[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]methyl]-1h-indole Chemical compound C=1C2=CC(F)=CC=C2NC=1CN(CC1)CCN1C1=CC=CC(C(F)(F)F)=C1 YXEZZMBABNHVFB-UHFFFAOYSA-N 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- HAEDOALGQUCLFO-UHFFFAOYSA-N 2-[[4-(6-chloropyridazin-3-yl)piperazin-1-yl]methyl]-5-fluoro-1h-indole Chemical compound C=1C2=CC(F)=CC=C2NC=1CN(CC1)CCN1C1=CC=C(Cl)N=N1 HAEDOALGQUCLFO-UHFFFAOYSA-N 0.000 claims description 3
- HHOWJZHPIBYIAE-UHFFFAOYSA-N 2-[[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]methyl]-1h-indole Chemical compound FC(F)(F)C1=CC=CC(N2CCN(CC=3NC4=CC=CC=C4C=3)CC2)=C1 HHOWJZHPIBYIAE-UHFFFAOYSA-N 0.000 claims description 3
- PQOIDBZLMJMYCD-UHFFFAOYSA-N 5-fluoro-2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1h-indole Chemical compound C=1C2=CC(F)=CC=C2NC=1CN(CC1)CCN1C1=CC=CC=N1 PQOIDBZLMJMYCD-UHFFFAOYSA-N 0.000 claims description 3
- MWPFXEHMGAJJCD-UHFFFAOYSA-N 5-fluoro-2-[[4-(4-fluorophenyl)piperazin-1-yl]methyl]-1h-indole Chemical compound C1=CC(F)=CC=C1N1CCN(CC=2NC3=CC=C(F)C=C3C=2)CC1 MWPFXEHMGAJJCD-UHFFFAOYSA-N 0.000 claims description 3
- 208000000323 Tourette Syndrome Diseases 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 2
- FRPJGTNLZNXQEX-UHFFFAOYSA-N 2-[[4-(2-pyridinyl)-1-piperazinyl]methyl]-1H-benzimidazole Chemical compound N=1C2=CC=CC=C2NC=1CN(CC1)CCN1C1=CC=CC=N1 FRPJGTNLZNXQEX-UHFFFAOYSA-N 0.000 claims description 2
- RRXFCJOMSDWWCA-UHFFFAOYSA-N 2-[[4-(4-fluorophenyl)piperazin-1-yl]methyl]-1h-benzimidazole Chemical compound C1=CC(F)=CC=C1N1CCN(CC=2NC3=CC=CC=C3N=2)CC1 RRXFCJOMSDWWCA-UHFFFAOYSA-N 0.000 claims description 2
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 2
- ZSKFERSPBICNGI-UHFFFAOYSA-N 6-fluoro-2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1h-benzimidazole Chemical compound N=1C2=CC(F)=CC=C2NC=1CN(CC1)CCN1C1=CC=CC=N1 ZSKFERSPBICNGI-UHFFFAOYSA-N 0.000 claims description 2
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 208000019116 sleep disease Diseases 0.000 claims 4
- 210000004211 gastric acid Anatomy 0.000 claims 1
- 239000003176 neuroleptic agent Substances 0.000 claims 1
- 230000028327 secretion Effects 0.000 claims 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 105
- 238000004458 analytical method Methods 0.000 description 63
- 235000011087 fumaric acid Nutrition 0.000 description 53
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 52
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 27
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
- -1 hydrocarbon radicals Chemical class 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 10
- 239000000243 solution Substances 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 239000000556 agonist Substances 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 5
- 239000003880 polar aprotic solvent Substances 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 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 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 108050004812 Dopamine receptor Proteins 0.000 description 4
- 102000015554 Dopamine receptor Human genes 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 230000027119 gastric acid secretion Effects 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- TZQTUVKKDQHARM-UHFFFAOYSA-N (5-fluoro-1h-indol-2-yl)-[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]methanone Chemical compound C=1C2=CC(F)=CC=C2NC=1C(=O)N(CC1)CCN1C1=CC=CC(C(F)(F)F)=C1 TZQTUVKKDQHARM-UHFFFAOYSA-N 0.000 description 3
- SUZLHDUTVMZSEV-UHFFFAOYSA-N Deoxycoleonol Natural products C12C(=O)CC(C)(C=C)OC2(C)C(OC(=O)C)C(O)C2C1(C)C(O)CCC2(C)C SUZLHDUTVMZSEV-UHFFFAOYSA-N 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 3
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- OHCQJHSOBUTRHG-UHFFFAOYSA-N colforsin Natural products OC12C(=O)CC(C)(C=C)OC1(C)C(OC(=O)C)C(O)C1C2(C)C(O)CCC1(C)C OHCQJHSOBUTRHG-UHFFFAOYSA-N 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 230000013016 learning Effects 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 230000015654 memory Effects 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- FTSUPYGMFAPCFZ-ZWNOBZJWSA-N quinpirole Chemical compound C([C@H]1CCCN([C@@H]1C1)CCC)C2=C1C=NN2 FTSUPYGMFAPCFZ-ZWNOBZJWSA-N 0.000 description 3
- 229950001037 quinpirole Drugs 0.000 description 3
- 230000007958 sleep Effects 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 230000005062 synaptic transmission Effects 0.000 description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- GWTRIXSVMJBFRD-UHFFFAOYSA-N 2-[(4-pyridin-2-ylpiperazin-1-yl)methyl]-1h-indole Chemical compound C=1C2=CC=CC=C2NC=1CN(CC1)CCN1C1=CC=CC=N1 GWTRIXSVMJBFRD-UHFFFAOYSA-N 0.000 description 2
- SVDHOCZCQXVPOU-UHFFFAOYSA-N 5-fluoro-1h-indole-2-carbaldehyde Chemical compound FC1=CC=C2NC(C=O)=CC2=C1 SVDHOCZCQXVPOU-UHFFFAOYSA-N 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 101000865206 Homo sapiens D(4) dopamine receptor Proteins 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 208000028017 Psychotic disease Diseases 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 208000016620 Tourette disease Diseases 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 125000002015 acyclic group Chemical group 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 208000015114 central nervous system disease Diseases 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 229910052681 coesite Inorganic materials 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 229910052906 cristobalite Inorganic materials 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 235000019439 ethyl acetate Nutrition 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 2
- USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 2
- 235000015110 jellies Nutrition 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 208000022610 schizoaffective disease Diseases 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 229910052682 stishovite Inorganic materials 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 229910052905 tridymite Inorganic materials 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- ZZJYIKPMDIWRSN-TZBSWOFLSA-N (+)-butaclamol Chemical compound C12=CC=CC=C2CCC2=CC=CC3=C2[C@@H]1CN1CC[C@@](C(C)(C)C)(O)C[C@@H]13 ZZJYIKPMDIWRSN-TZBSWOFLSA-N 0.000 description 1
- GIPXMXAYTYHIKL-UHFFFAOYSA-N (5-fluoro-1h-indol-2-yl)-(4-pyridin-2-ylpiperazin-1-yl)methanone Chemical compound C=1C2=CC(F)=CC=C2NC=1C(=O)N(CC1)CCN1C1=CC=CC=N1 GIPXMXAYTYHIKL-UHFFFAOYSA-N 0.000 description 1
- ONCQOAGPACYSDJ-UHFFFAOYSA-N (5-fluoro-1h-indol-2-yl)-[4-(2-nitrophenyl)piperazin-1-yl]methanone Chemical compound [O-][N+](=O)C1=CC=CC=C1N1CCN(C(=O)C=2NC3=CC=C(F)C=C3C=2)CC1 ONCQOAGPACYSDJ-UHFFFAOYSA-N 0.000 description 1
- UWTJARDNAKLKCS-ZXVVBBHZSA-N (e)-1-(4-tert-butylphenyl)-n-[4-(naphthalen-1-ylmethyl)piperazin-1-yl]methanimine Chemical compound C1=CC(C(C)(C)C)=CC=C1\C=N\N1CCN(CC=2C3=CC=CC=C3C=CC=2)CC1 UWTJARDNAKLKCS-ZXVVBBHZSA-N 0.000 description 1
- VHFVKMTVMIZMIK-UHFFFAOYSA-N 1-(3-chlorophenyl)piperazine Chemical compound ClC1=CC=CC(N2CCNCC2)=C1 VHFVKMTVMIZMIK-UHFFFAOYSA-N 0.000 description 1
- FISMTDVFYIMUBI-UHFFFAOYSA-N 1h-indol-2-yl-(4-pyridin-2-ylpiperazin-1-yl)methanone Chemical compound C=1C2=CC=CC=C2NC=1C(=O)N(CC1)CCN1C1=CC=CC=N1 FISMTDVFYIMUBI-UHFFFAOYSA-N 0.000 description 1
- RXFRHGBGKRBRJO-UHFFFAOYSA-N 1h-indol-2-yl-[4-(2-nitrophenyl)piperazin-1-yl]methanone Chemical compound [O-][N+](=O)C1=CC=CC=C1N1CCN(C(=O)C=2NC3=CC=CC=C3C=2)CC1 RXFRHGBGKRBRJO-UHFFFAOYSA-N 0.000 description 1
- NRZMEMYHVIKKHS-UHFFFAOYSA-N 2-[(4-naphthalen-1-ylpiperazin-1-yl)methyl]-1h-indole Chemical compound C1=CC=C2NC(CN3CCN(CC3)C=3C4=CC=CC=C4C=CC=3)=CC2=C1 NRZMEMYHVIKKHS-UHFFFAOYSA-N 0.000 description 1
- PZTWBYCZTVLVPV-UHFFFAOYSA-N 2-[2-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCCC1CNCCN1CCS(O)(=O)=O PZTWBYCZTVLVPV-UHFFFAOYSA-N 0.000 description 1
- QKBNNXLRXRSCOW-UHFFFAOYSA-N 2-[[4-(2-nitrophenyl)piperazin-1-yl]methyl]-1h-indole Chemical compound [O-][N+](=O)C1=CC=CC=C1N1CCN(CC=2NC3=CC=CC=C3C=2)CC1 QKBNNXLRXRSCOW-UHFFFAOYSA-N 0.000 description 1
- CWQOSWBNXOLUEQ-UHFFFAOYSA-N 2-[[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]methyl]-1h-indol-5-ol Chemical compound C=1C2=CC(O)=CC=C2NC=1CN(CC1)CCN1C1=CC=CC(C(F)(F)F)=C1 CWQOSWBNXOLUEQ-UHFFFAOYSA-N 0.000 description 1
- JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
- APIXJSLKIYYUKG-UHFFFAOYSA-N 3 Isobutyl 1 methylxanthine Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N=CN2 APIXJSLKIYYUKG-UHFFFAOYSA-N 0.000 description 1
- JYJAHLMLMXZTEH-UHFFFAOYSA-N 3-[4-(1h-indol-2-ylmethyl)piperazin-1-yl]-1,2-benzothiazole Chemical compound C1=CC=C2NC(CN3CCN(CC3)C=3C4=CC=CC=C4SN=3)=CC2=C1 JYJAHLMLMXZTEH-UHFFFAOYSA-N 0.000 description 1
- SDZBAXLIHRBNOV-UHFFFAOYSA-N 5-fluoro-1h-indole-3-carboxylic acid Chemical compound C1=C(F)C=C2C(C(=O)O)=CNC2=C1 SDZBAXLIHRBNOV-UHFFFAOYSA-N 0.000 description 1
- WZACPVLYMQHASB-UHFFFAOYSA-N 5-fluoro-2-[(4-naphthalen-1-ylpiperazin-1-yl)methyl]-1h-indole Chemical compound C1=CC=C2C(N3CCN(CC3)CC=3NC4=CC=C(C=C4C=3)F)=CC=CC2=C1 WZACPVLYMQHASB-UHFFFAOYSA-N 0.000 description 1
- QSBOGUJMCZHCOI-UHFFFAOYSA-N 5-fluoro-2-[[4-(2-nitrophenyl)piperazin-1-yl]methyl]-1h-indole Chemical compound [O-][N+](=O)C1=CC=CC=C1N1CCN(CC=2NC3=CC=C(F)C=C3C=2)CC1 QSBOGUJMCZHCOI-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
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 1
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 1
- 208000020925 Bipolar disease Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 108090000357 Dopamine D4 receptors Proteins 0.000 description 1
- 102000003962 Dopamine D4 receptors Human genes 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 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 1
- 239000004471 Glycine Substances 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 1
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 229910010082 LiAlH Inorganic materials 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 229940099471 Phosphodiesterase inhibitor Drugs 0.000 description 1
- 244000000231 Sesamum indicum Species 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 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
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 102000030621 adenylate cyclase Human genes 0.000 description 1
- 108060000200 adenylate cyclase Proteins 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000005910 alkyl carbonate group Chemical group 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- UORVGPXVDQYIDP-BJUDXGSMSA-N borane Chemical class [10BH3] UORVGPXVDQYIDP-BJUDXGSMSA-N 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 230000001593 cAMP accumulation Effects 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 229960003563 calcium carbonate Drugs 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000002475 cognitive enhancer Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 229940126513 cyclase activator Drugs 0.000 description 1
- 229940095074 cyclic amp Drugs 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 229940005501 dopaminergic agent Drugs 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000035611 feeding Effects 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 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
- 235000011187 glycerol Nutrition 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- OWYJZQFASFWUHP-UHFFFAOYSA-N hydroxylamine;1h-indole Chemical compound ON.C1=CC=C2NC=CC2=C1 OWYJZQFASFWUHP-UHFFFAOYSA-N 0.000 description 1
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 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
- 239000011261 inert gas Substances 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000008183 oral pharmaceutical preparation Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 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
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000029865 regulation of blood pressure Effects 0.000 description 1
- 230000012121 regulation of immune response Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000009329 sexual behaviour Effects 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 229960001790 sodium citrate Drugs 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 108010092215 spiroperidol receptor Proteins 0.000 description 1
- 239000007921 spray Substances 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
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup 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
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- 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
- A61P25/18—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
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic 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
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Addiction (AREA)
- Ophthalmology & Optometry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Anesthesiology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US5576497P | 1997-08-15 | 1997-08-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP980441A2 true HRP980441A2 (en) | 1999-04-30 |
Family
ID=22000003
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR60/055,764A HRP980441A2 (en) | 1997-08-15 | 1998-08-14 | 2-(4-aryl or heteroaryl-piperazin-1-ylmethyl)-1h-indole derivatives |
Country Status (30)
| Country | Link |
|---|---|
| EP (1) | EP1003739A2 (es) |
| JP (1) | JP2002536291A (es) |
| KR (1) | KR20010022507A (es) |
| CN (1) | CN1265660A (es) |
| AP (1) | AP9801321A0 (es) |
| AR (1) | AR017019A1 (es) |
| AU (1) | AU8457298A (es) |
| BG (1) | BG104069A (es) |
| BR (1) | BR9811557A (es) |
| CA (1) | CA2297486C (es) |
| CO (1) | CO4960656A1 (es) |
| DZ (1) | DZ2583A1 (es) |
| EA (1) | EA200000023A1 (es) |
| HR (1) | HRP980441A2 (es) |
| HU (1) | HUP0003425A3 (es) |
| ID (1) | ID23803A (es) |
| IL (1) | IL133960A0 (es) |
| IS (1) | IS5336A (es) |
| MA (1) | MA24632A1 (es) |
| NO (1) | NO20000722L (es) |
| OA (1) | OA11286A (es) |
| PA (1) | PA8457001A1 (es) |
| PE (1) | PE106299A1 (es) |
| PL (1) | PL338947A1 (es) |
| SK (1) | SK1352000A3 (es) |
| TN (1) | TNSN98151A1 (es) |
| TR (1) | TR200000414T2 (es) |
| UY (1) | UY25144A1 (es) |
| WO (1) | WO1999009025A2 (es) |
| ZA (1) | ZA987304B (es) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EE04588B1 (et) * | 1997-10-27 | 2006-02-15 | Neurosearch A/S | Heteroarüüldiasatsükloalkaanid kui atsetüülkoliini nikotiinretseptorite kolinergilised ligandid, nende kasutamine ravimitena ning neid sisaldav farmatseutiline kompositsioon |
| EP0953567A3 (en) | 1998-04-29 | 2003-04-02 | Pfizer Products Inc. | Bicyclic substituted piperazine-, piperidine- and tetrahydropyridine derivatives, their preparation and their use as agents with central dopaminergic (dopamine D4 receptor) activity |
| UA73756C2 (en) | 1999-12-30 | 2005-09-15 | Lundbeck & Co As H | HALOGEN-SUBSTITUTED 4-PHENYL-1-PIPERAZIN, PIPERIDIN AND TETRAHYDROPIRIDINE û DERIVATIVES A PHARMACEUTICAL COMPOSITION BASED THEREON, THEIR APPLICATION FOR PRODUCING MEDICAMENT, AND A METHOD FOR THE TREATMENT OF PSYCHOSIS |
| GB0017952D0 (en) * | 2000-07-22 | 2000-09-13 | Univ Manchester | Treatment of dyskinesia |
| EP1177792A3 (en) | 2000-07-27 | 2002-10-23 | Pfizer Products Inc. | Dopamine D4 Ligands for the treatment of novelty-seeking disorders |
| US6803362B2 (en) | 2001-03-09 | 2004-10-12 | Ortho-Mcneil Pharmaceutical Inc. | Heterocyclic compounds |
| JP2006500390A (ja) | 2002-09-06 | 2006-01-05 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 複素環式化合物 |
| WO2004108671A1 (en) * | 2003-06-06 | 2004-12-16 | Suven Life Sciences Limited | Substituted indoles with serotonin receptor affinity, process for their preparation and pharmaceutical compositions containing them |
| WO2005095338A1 (ja) | 2004-03-30 | 2005-10-13 | Takeda Pharmaceutical Company Limited | アルコキシフェニルプロパン酸誘導体 |
| US7572805B2 (en) | 2004-07-14 | 2009-08-11 | Bristol-Myers Squibb Company | Pyrrolo(oxo)isoquinolines as 5HT ligands |
| US7618980B2 (en) | 2004-07-14 | 2009-11-17 | Bristol-Myers Squibb Company | Pyrrolo(oxo)quinolines as 5HT ligands |
| JO2769B1 (en) * | 2005-10-26 | 2014-03-15 | جانسين فارماسوتيكا ان. في | Rapid decomposition of physiologically antagonistic agents of the 2-dopamine receptor |
| JO2642B1 (en) * | 2006-12-08 | 2012-06-17 | جانسين فارماسوتيكا ان. في | Dopamine 2 receptor antagonists are rapidly hydrolyzed |
| JO2849B1 (en) | 2007-02-13 | 2015-03-15 | جانسين فارماسوتيكا ان. في | Dopamine 2 receptor antagonists are rapidly hydrolyzed |
| WO2008128995A1 (en) | 2007-04-23 | 2008-10-30 | Janssen Pharmaceutica N.V. | 4-alkoxypyridazine derivatives as fast dissociating dopamine 2 receptor antagonists |
| US8933101B2 (en) | 2007-04-23 | 2015-01-13 | Janssen Pharmaceutica Nv | Thia(dia)zoles as fast dissociating dopamine 2 receptor antagonists |
| WO2010000456A1 (en) | 2008-07-03 | 2010-01-07 | Janssen Pharmaceutica Nv | Substituted 6- (1-piperazinyl) -pyridazines as 5-ht6 receptor antagonists |
| US8895562B2 (en) | 2008-07-31 | 2014-11-25 | Janssen Pharmaceutica Nv | Piperazin-1-yl-trifluoromethyl-substituted-pyridines as fast dissociating dopamine 2 receptor antagonists |
| CN109843872B (zh) * | 2017-09-20 | 2022-08-30 | 杭州英创医药科技有限公司 | 作为ido抑制剂和/或ido-hdac双重抑制剂的多环化合物 |
| CA3171950A1 (en) * | 2020-04-22 | 2021-10-28 | David William Sheppard | Collagen 1 translation inhibitors and methods of use thereof |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB944443A (es) * | 1959-09-25 | 1900-01-01 | ||
| KR100236808B1 (ko) * | 1991-07-03 | 2000-02-01 | 로렌스 티. 마이젠헬더 | 에이즈 치료약제로서의 치환된 인돌 |
| JPH05255089A (ja) * | 1991-12-18 | 1993-10-05 | Sanwa Kagaku Kenkyusho Co Ltd | 抗ウイルス剤 |
| US5670522A (en) * | 1992-10-23 | 1997-09-23 | Merck Sharp & Dohme Limited | Dopamine receptor subtype ligands |
| GB9305644D0 (en) * | 1993-03-18 | 1993-05-05 | Merck Sharp & Dohme | Therapeutic agents |
| US5576336A (en) * | 1993-03-18 | 1996-11-19 | Merck Sharp & Dohme Limited | Indole derivatives as dopamine D4 antagonists |
| US5814644A (en) * | 1993-04-15 | 1998-09-29 | Merck Sharp & Dohme, Ltd. | Indole derivatives as dopamine D4 antagonists |
| DE4414113A1 (de) * | 1994-04-22 | 1995-10-26 | Merck Patent Gmbh | 3-Indolylpiperidine |
| TW406075B (en) * | 1994-12-13 | 2000-09-21 | Upjohn Co | Alkyl substituted piperidinyl and piperazinyl anti-AIDS compounds |
| ZA968661B (en) * | 1995-11-17 | 1998-04-14 | Upjohn Co | Oxazolidinone antibacterial agent with tricyclic substituents. |
| TW504510B (en) * | 1996-05-10 | 2002-10-01 | Janssen Pharmaceutica Nv | 2,4-diaminopyrimidine derivatives |
-
1998
- 1998-08-05 AU AU84572/98A patent/AU8457298A/en not_active Abandoned
- 1998-08-05 KR KR1020007001093A patent/KR20010022507A/ko not_active Application Discontinuation
- 1998-08-05 SK SK135-2000A patent/SK1352000A3/sk unknown
- 1998-08-05 BR BR9811557-0A patent/BR9811557A/pt not_active IP Right Cessation
- 1998-08-05 WO PCT/IB1998/001198 patent/WO1999009025A2/en not_active Application Discontinuation
- 1998-08-05 EA EA200000023A patent/EA200000023A1/ru unknown
- 1998-08-05 PL PL98338947A patent/PL338947A1/xx unknown
- 1998-08-05 AP APAP/P/1998/001321A patent/AP9801321A0/en unknown
- 1998-08-05 ID IDW20000197A patent/ID23803A/id unknown
- 1998-08-05 CN CN98807831A patent/CN1265660A/zh active Pending
- 1998-08-05 TR TR2000/00414T patent/TR200000414T2/xx unknown
- 1998-08-05 IL IL13396098A patent/IL133960A0/xx unknown
- 1998-08-05 JP JP2000509706A patent/JP2002536291A/ja active Pending
- 1998-08-05 EP EP98935229A patent/EP1003739A2/en not_active Withdrawn
- 1998-08-05 CA CA002297486A patent/CA2297486C/en not_active Expired - Fee Related
- 1998-08-05 HU HU0003425A patent/HUP0003425A3/hu unknown
- 1998-08-10 PE PE1998000717A patent/PE106299A1/es not_active Application Discontinuation
- 1998-08-10 PA PA19988457001A patent/PA8457001A1/es unknown
- 1998-08-12 TN TNTNSN98151A patent/TNSN98151A1/fr unknown
- 1998-08-12 MA MA25210A patent/MA24632A1/fr unknown
- 1998-08-12 DZ DZ980193A patent/DZ2583A1/xx active
- 1998-08-13 AR ARP980104021A patent/AR017019A1/es unknown
- 1998-08-14 HR HR60/055,764A patent/HRP980441A2/hr not_active Application Discontinuation
- 1998-08-14 ZA ZA9807304A patent/ZA987304B/xx unknown
- 1998-08-14 CO CO98046788A patent/CO4960656A1/es unknown
- 1998-08-17 UY UY25144A patent/UY25144A1/es not_active Application Discontinuation
-
2000
- 2000-01-10 BG BG104069A patent/BG104069A/xx unknown
- 2000-01-11 IS IS5336A patent/IS5336A/is unknown
- 2000-02-08 OA OA1200000030A patent/OA11286A/en unknown
- 2000-02-14 NO NO20000722A patent/NO20000722L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| OA11286A (en) | 2003-10-22 |
| CA2297486C (en) | 2005-05-03 |
| ZA987304B (en) | 2000-02-14 |
| EP1003739A2 (en) | 2000-05-31 |
| NO20000722D0 (no) | 2000-02-14 |
| PA8457001A1 (es) | 2000-09-29 |
| EA200000023A1 (ru) | 2000-08-28 |
| UY25144A1 (es) | 2000-12-29 |
| HUP0003425A3 (en) | 2002-02-28 |
| CA2297486A1 (en) | 1999-02-25 |
| DZ2583A1 (fr) | 2003-02-22 |
| BG104069A (en) | 2001-05-31 |
| AP9801321A0 (en) | 2000-02-14 |
| KR20010022507A (ko) | 2001-03-15 |
| JP2002536291A (ja) | 2002-10-29 |
| TNSN98151A1 (fr) | 2005-03-15 |
| BR9811557A (pt) | 2000-08-22 |
| SK1352000A3 (en) | 2000-08-14 |
| AU8457298A (en) | 1999-03-08 |
| PL338947A1 (en) | 2000-12-04 |
| CO4960656A1 (es) | 2000-09-25 |
| NO20000722L (no) | 2000-02-14 |
| TR200000414T2 (tr) | 2000-08-21 |
| MA24632A1 (fr) | 1999-04-01 |
| HUP0003425A2 (hu) | 2001-10-28 |
| WO1999009025A3 (en) | 1999-04-15 |
| IS5336A (is) | 2000-01-11 |
| IL133960A0 (en) | 2001-04-30 |
| ID23803A (id) | 2000-05-11 |
| WO1999009025A2 (en) | 1999-02-25 |
| CN1265660A (zh) | 2000-09-06 |
| PE106299A1 (es) | 1999-11-02 |
| AR017019A1 (es) | 2001-08-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| HRP980441A2 (en) | 2-(4-aryl or heteroaryl-piperazin-1-ylmethyl)-1h-indole derivatives | |
| TW502034B (en) | 2-aryl-8-oxodihydropurine derivative, process for the preparation thereof, pharmaceutical composition containing the same, and intermediate therefor | |
| KR100969402B1 (ko) | Ｉ형 글리신 수송 억제제로서의 비시클릭 [3.1.0]헤테로아릴 아미드 | |
| US6472392B1 (en) | Triazole compounds and the use thereof as dopamine-D3 -ligands | |
| US5681956A (en) | 4-aryl substituted piperazinylmethyl phenylimidazole derivatives; a new class of dopamine receptor subtype specific ligands | |
| CZ20032614A3 (en) | N-(2-arylethyl) benzylamines as antagonists of the 5-ht6 receptor | |
| US8044069B2 (en) | Compounds as calcium channel blockers | |
| WO2005079791A1 (en) | Thiophene -2- carboxylic acid - (1h - benzimidazol - 2 yl) - amide derivatives and related compounds as inhibitors of the tec kinase itk (interleukin -2- inducible t cell kinase) for the treatment of inflammation, immunological and allergic disorders | |
| CA2192975C (en) | Benzimidazolone derivatives | |
| AU2007307105A1 (en) | N-substituted-azacyclylamines as histamine-3 antagonists | |
| EP2245016A1 (en) | Substituted amino-benzimidazoles, medicaments comprising said compound, their use and their method of manufacture | |
| JP3004727B2 (ja) | ドパミン作動性活性を有するベンゾイミダゾール誘導体 | |
| Andersen et al. | Selective, centrally acting serotonin 5-HT2 antagonists. 2. Substituted 3-(4-fluorophenyl)-1H-indoles | |
| TW200901983A (en) | Azacyclylbenzamide derivatives as histamine-3 antagonists | |
| AU2002300094B2 (en) | New octahydro-2H-pyrido[1,2-alpha]pyrazine compounds, a process for their preparation and pharmaceutical compositions containing them | |
| CA2346896C (en) | 3-tetrahydropyridin-4-yl indoles for treatment of psychotic disorders | |
| CA1177830A (en) | Hexahydro-trans- and tetrahydropyridoindole neuroleptic agents | |
| HRP950507A2 (en) | 2,7-SUBSTITUTED OCTAHYDRO-1H-PYRIDO(1,2-a)PYRAZINE DERIVATIVES | |
| WO1999021848A2 (en) | Novel 1-(n'-(arylalkylaminoalkyl))aminoisoindoles; a new class of dopamine receptor subtype specific ligands | |
| US20040198734A1 (en) | 2-(4-Aryl or heteroaryl-piperazin-1-ylmethyl)-1H-indole derivatives interacting with the dopamine | |
| RU2423360C2 (ru) | Производные индола как ингибиторы н3-рецептора гистамина для лечения когнитивных расстройств и нарушений сна, ожирения и других расстройств центральной нервной системы | |
| SK42299A3 (en) | N-(benzothiazol-2-yl) piperidine-1-ethanamine derivatives, their preparation and application in therapeutics | |
| US6031097A (en) | 1-(N-(arylalkylaminoalkyl) aminoisoquinolines; a new class of dopamine receptor subtype specific ligands | |
| TWI294778B (en) | Peptide deformylase inhibitors | |
| CA2498215A1 (en) | Oxindole substituted piperazine derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AIPI | Request for the grant of a patent on the basis of a substantive examination of a patent application | ||
| A1OB | Publication of a patent application | ||
| ODRP | Renewal fee for the maintenance of a patent |
Payment date: 20000814 Year of fee payment: 3 |
|
| ODBI | Application refused |