ES2386168T3 - Derivados de pirazoloquinolina terapéuticos - Google Patents
Derivados de pirazoloquinolina terapéuticos Download PDFInfo
- Publication number
- ES2386168T3 ES2386168T3 ES08770402T ES08770402T ES2386168T3 ES 2386168 T3 ES2386168 T3 ES 2386168T3 ES 08770402 T ES08770402 T ES 08770402T ES 08770402 T ES08770402 T ES 08770402T ES 2386168 T3 ES2386168 T3 ES 2386168T3
- Authority
- ES
- Spain
- Prior art keywords
- formula
- compound
- alkyl
- aryl
- optionally substituted
- 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.)
- Active
Links
- UXYHZIYEDDINQH-UHFFFAOYSA-N C1=CNC2=C3C=NN=C3C=CC2=C1 Chemical class C1=CNC2=C3C=NN=C3C=CC2=C1 UXYHZIYEDDINQH-UHFFFAOYSA-N 0.000 title description 6
- 230000001225 therapeutic effect Effects 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 286
- 241001465754 Metazoa Species 0.000 claims abstract description 46
- 150000003839 salts Chemical class 0.000 claims description 75
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 60
- 229910052757 nitrogen Inorganic materials 0.000 claims description 52
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 46
- 229910052731 fluorine Inorganic materials 0.000 claims description 46
- 239000011737 fluorine Substances 0.000 claims description 46
- 229910052739 hydrogen Inorganic materials 0.000 claims description 40
- 125000003118 aryl group Chemical group 0.000 claims description 39
- 239000001257 hydrogen Substances 0.000 claims description 38
- -1 -C (O) O-aryl Chemical group 0.000 claims description 35
- 125000000623 heterocyclic group Chemical group 0.000 claims description 32
- 125000001072 heteroaryl group Chemical group 0.000 claims description 29
- 239000000203 mixture Substances 0.000 claims description 28
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 27
- 230000015654 memory Effects 0.000 claims description 24
- 238000002360 preparation method Methods 0.000 claims description 21
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 20
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 17
- 229910003827 NRaRb Inorganic materials 0.000 claims description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 150000002367 halogens Chemical group 0.000 claims description 15
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 239000001301 oxygen Substances 0.000 claims description 13
- 229960003692 gamma aminobutyric acid Drugs 0.000 claims description 11
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims description 11
- 208000010877 cognitive disease Diseases 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 230000003920 cognitive function Effects 0.000 claims description 7
- 229940079593 drug Drugs 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- 239000011593 sulfur Substances 0.000 claims description 7
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 125000004043 oxo group Chemical group O=* 0.000 claims description 6
- 208000020016 psychiatric disease Diseases 0.000 claims description 6
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 5
- 230000007787 long-term memory Effects 0.000 claims description 5
- 230000006403 short-term memory Effects 0.000 claims description 5
- 201000000980 schizophrenia Diseases 0.000 claims description 4
- 208000019901 Anxiety disease Diseases 0.000 claims description 3
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 3
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 229910052705 radium Inorganic materials 0.000 claims description 3
- 229910052701 rubidium Inorganic materials 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 208000035475 disorder Diseases 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 229910052702 rhenium Inorganic materials 0.000 claims description 2
- 208000019116 sleep disease Diseases 0.000 claims description 2
- 208000020685 sleep-wake disease Diseases 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 5
- 125000006728 (C1-C6) alkynyl group Chemical group 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 151
- 102000027484 GABAA receptors Human genes 0.000 abstract description 10
- 108091008681 GABAA receptors Proteins 0.000 abstract description 10
- 229940049706 benzodiazepine Drugs 0.000 abstract description 6
- 230000027455 binding Effects 0.000 abstract description 6
- 239000000126 substance Substances 0.000 abstract description 6
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 abstract description 5
- 229910052740 iodine Inorganic materials 0.000 abstract description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 168
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 108
- 238000005160 1H NMR spectroscopy Methods 0.000 description 99
- 239000002904 solvent Substances 0.000 description 74
- 230000015572 biosynthetic process Effects 0.000 description 61
- 238000003786 synthesis reaction Methods 0.000 description 60
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 56
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 52
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 50
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 48
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical group CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 48
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 42
- 238000010992 reflux Methods 0.000 description 40
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 36
- 238000006243 chemical reaction Methods 0.000 description 36
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 34
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 32
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 25
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 25
- 239000003795 chemical substances by application Substances 0.000 description 24
- 229940078552 o-xylene Drugs 0.000 description 24
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 22
- 238000005660 chlorination reaction Methods 0.000 description 22
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 22
- 239000000243 solution Substances 0.000 description 21
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 20
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 18
- 238000012549 training Methods 0.000 description 17
- 238000000159 protein binding assay Methods 0.000 description 15
- 150000001412 amines Chemical class 0.000 description 14
- 239000008096 xylene Substances 0.000 description 14
- 150000003738 xylenes Chemical class 0.000 description 14
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 13
- SCZNXLWKYFICFV-UHFFFAOYSA-N 1,2,3,4,5,7,8,9-octahydropyrido[1,2-b]diazepine Chemical compound C1CCCNN2CCCC=C21 SCZNXLWKYFICFV-UHFFFAOYSA-N 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 12
- 230000003197 catalytic effect Effects 0.000 description 12
- 150000003254 radicals Chemical class 0.000 description 12
- OFUFXTHGZWIDDB-UHFFFAOYSA-N 2-chloroquinoline Chemical compound C1=CC=CC2=NC(Cl)=CC=C21 OFUFXTHGZWIDDB-UHFFFAOYSA-N 0.000 description 11
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 11
- 239000012320 chlorinating reagent Substances 0.000 description 11
- 210000000287 oocyte Anatomy 0.000 description 11
- 150000007530 organic bases Chemical class 0.000 description 11
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 11
- 229940067157 phenylhydrazine Drugs 0.000 description 11
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 11
- JEXVQSWXXUJEMA-UHFFFAOYSA-N pyrazol-3-one Chemical compound O=C1C=CN=N1 JEXVQSWXXUJEMA-UHFFFAOYSA-N 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 11
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 10
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 10
- 125000004122 cyclic group Chemical group 0.000 description 10
- 238000006073 displacement reaction Methods 0.000 description 10
- 238000010438 heat treatment Methods 0.000 description 10
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical compound C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- TYMLOMAKGOJONV-UHFFFAOYSA-N 4-nitroaniline Chemical compound NC1=CC=C([N+]([O-])=O)C=C1 TYMLOMAKGOJONV-UHFFFAOYSA-N 0.000 description 8
- 125000005842 heteroatom Chemical group 0.000 description 8
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 8
- 230000014759 maintenance of location Effects 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 238000009835 boiling Methods 0.000 description 7
- 210000004556 brain Anatomy 0.000 description 7
- 239000002552 dosage form Substances 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- 238000007363 ring formation reaction Methods 0.000 description 7
- 230000002194 synthesizing effect Effects 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 125000004965 chloroalkyl group Chemical group 0.000 description 6
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 6
- 235000011150 stannous chloride Nutrition 0.000 description 6
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 6
- WHKWMTXTYKVFLK-UHFFFAOYSA-N 1-propan-2-ylpiperazine Chemical compound CC(C)N1CCNCC1 WHKWMTXTYKVFLK-UHFFFAOYSA-N 0.000 description 5
- 208000024827 Alzheimer disease Diseases 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 239000002299 complementary DNA Substances 0.000 description 5
- LTMHNWPUDSTBKD-UHFFFAOYSA-N diethyl 2-(ethoxymethylidene)propanedioate Chemical compound CCOC=C(C(=O)OCC)C(=O)OCC LTMHNWPUDSTBKD-UHFFFAOYSA-N 0.000 description 5
- VMKVYBOEHDTOKK-UHFFFAOYSA-N ethyl 4-chloro-7,8-difluoroquinoline-3-carboxylate Chemical compound FC1=C(F)C=CC2=C(Cl)C(C(=O)OCC)=CN=C21 VMKVYBOEHDTOKK-UHFFFAOYSA-N 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 231100000252 nontoxic Toxicity 0.000 description 5
- 230000003000 nontoxic effect Effects 0.000 description 5
- PVRSIFAEUCUJPK-UHFFFAOYSA-N (4-methoxyphenyl)hydrazine Chemical compound COC1=CC=C(NN)C=C1 PVRSIFAEUCUJPK-UHFFFAOYSA-N 0.000 description 4
- UJIAYFCOYFTLAK-UHFFFAOYSA-N 2-chloro-3-fluoroquinoline Chemical compound C1=CC=C2N=C(Cl)C(F)=CC2=C1 UJIAYFCOYFTLAK-UHFFFAOYSA-N 0.000 description 4
- ONFOBSDFWDUQGR-UHFFFAOYSA-N 4-pyrazolo[3,4-h]quinolin-7-ylmorpholine Chemical compound C1COCCN1N1C(C=CC=2C3=NC=CC=2)=C3C=N1 ONFOBSDFWDUQGR-UHFFFAOYSA-N 0.000 description 4
- PUYNFTFNPOMBQE-UHFFFAOYSA-N 4-pyrazolo[3,4-h]quinolin-8-ylmorpholine Chemical compound C1COCCN1N1N=C(C=CC=2C3=NC=CC=2)C3=C1 PUYNFTFNPOMBQE-UHFFFAOYSA-N 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- 241000283984 Rodentia Species 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000000556 agonist Substances 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- TXFLGZOGNOOEFZ-UHFFFAOYSA-N bis(2-chloroethyl)amine Chemical class ClCCNCCCl TXFLGZOGNOOEFZ-UHFFFAOYSA-N 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
- 239000010949 copper Substances 0.000 description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 238000003379 elimination reaction Methods 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 3
- OVSKIKFHRZPJSS-UHFFFAOYSA-N 2,4-D Chemical compound OC(=O)COC1=CC=C(Cl)C=C1Cl OVSKIKFHRZPJSS-UHFFFAOYSA-N 0.000 description 3
- MFVFHEUMUABMCF-UHFFFAOYSA-N 2-chloro-3,4-difluoroquinoline Chemical compound C1=CC=C2N=C(Cl)C(F)=C(F)C2=C1 MFVFHEUMUABMCF-UHFFFAOYSA-N 0.000 description 3
- 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 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- HSBJIKXOQZANSH-UHFFFAOYSA-N C12=C(N3CCOCC3)C(F)=C(N3CCOCC3)C=C2NC=C(C2=O)C1=NN2C1=CC=CC=C1 Chemical compound C12=C(N3CCOCC3)C(F)=C(N3CCOCC3)C=C2NC=C(C2=O)C1=NN2C1=CC=CC=C1 HSBJIKXOQZANSH-UHFFFAOYSA-N 0.000 description 3
- HLKUBVKKYWVHRS-UHFFFAOYSA-N C12=CC(F)=CC(F)=C2NC=C(C2=O)C1=NN2C1=CC=CC=C1 Chemical compound C12=CC(F)=CC(F)=C2NC=C(C2=O)C1=NN2C1=CC=CC=C1 HLKUBVKKYWVHRS-UHFFFAOYSA-N 0.000 description 3
- KRMNTYLXBATHJB-UHFFFAOYSA-N C12=CC(N)=CC=C2NC=C(C2=O)C1=NN2C1=CC=CC=C1 Chemical compound C12=CC(N)=CC=C2NC=C(C2=O)C1=NN2C1=CC=CC=C1 KRMNTYLXBATHJB-UHFFFAOYSA-N 0.000 description 3
- JJEAMUGKJQFDLV-UHFFFAOYSA-N C1=2C(F)=C(F)C(F)=CC=2NC=C(C2=O)C1=NN2C1=CC=CC=C1 Chemical compound C1=2C(F)=C(F)C(F)=CC=2NC=C(C2=O)C1=NN2C1=CC=CC=C1 JJEAMUGKJQFDLV-UHFFFAOYSA-N 0.000 description 3
- VQPSOUYQHMVJHH-UHFFFAOYSA-N C1=CC(Cl)=CC=C1N1C(=O)C2=CNC3=CC(N4CCNCC4)=CC=C3C2=N1 Chemical compound C1=CC(Cl)=CC=C1N1C(=O)C2=CNC3=CC(N4CCNCC4)=CC=C3C2=N1 VQPSOUYQHMVJHH-UHFFFAOYSA-N 0.000 description 3
- PNJBEVVSHRUEJL-UHFFFAOYSA-N C1CN(C)CCN1C1=CC(F)=CC2=C1NC=C1C(=O)N(C=3C=CC=CC=3)N=C12 Chemical compound C1CN(C)CCN1C1=CC(F)=CC2=C1NC=C1C(=O)N(C=3C=CC=CC=3)N=C12 PNJBEVVSHRUEJL-UHFFFAOYSA-N 0.000 description 3
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 3
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- NKCOMUPHPBBTRP-UHFFFAOYSA-N O=C1C2=C(C)NC3=CC(F)=C(F)C=C3C2=NN1C1=CC=CC=C1 Chemical compound O=C1C2=C(C)NC3=CC(F)=C(F)C=C3C2=NN1C1=CC=CC=C1 NKCOMUPHPBBTRP-UHFFFAOYSA-N 0.000 description 3
- KPHHLWSLDKXZGJ-UHFFFAOYSA-N O=C1C2=CNC=3C(F)=CC(C(F)(F)F)=CC=3C2=NN1C1=CC=CC=C1 Chemical compound O=C1C2=CNC=3C(F)=CC(C(F)(F)F)=CC=3C2=NN1C1=CC=CC=C1 KPHHLWSLDKXZGJ-UHFFFAOYSA-N 0.000 description 3
- FLSMHPYAGBVZKF-UHFFFAOYSA-N O=C1C2=CNC=3C(N)=CC(F)=CC=3C2=NN1C1=CC=CC=C1 Chemical compound O=C1C2=CNC=3C(N)=CC(F)=CC=3C2=NN1C1=CC=CC=C1 FLSMHPYAGBVZKF-UHFFFAOYSA-N 0.000 description 3
- ATIFGOYHAAAXBE-UHFFFAOYSA-N O=C1C2=CNC=3C([N+](=O)[O-])=CC(F)=CC=3C2=NN1C1=CC=CC=C1 Chemical compound O=C1C2=CNC=3C([N+](=O)[O-])=CC(F)=CC=3C2=NN1C1=CC=CC=C1 ATIFGOYHAAAXBE-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229910019020 PtO2 Inorganic materials 0.000 description 3
- 239000007868 Raney catalyst Substances 0.000 description 3
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 3
- 229910000564 Raney nickel Inorganic materials 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 3
- 125000005418 aryl aryl group Chemical group 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 230000003542 behavioural effect Effects 0.000 description 3
- 125000002619 bicyclic group Chemical group 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- 125000002603 chloroethyl group Chemical group [H]C([*])([H])C([H])([H])Cl 0.000 description 3
- 229910052802 copper Inorganic materials 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 230000007831 electrophysiology Effects 0.000 description 3
- 238000002001 electrophysiology Methods 0.000 description 3
- 150000002081 enamines Chemical class 0.000 description 3
- WCFMOGCTVPWEFW-UHFFFAOYSA-N ethyl 4-chloro-6,7,8-trifluoroquinoline-3-carboxylate Chemical compound FC1=C(F)C(F)=CC2=C(Cl)C(C(=O)OCC)=CN=C21 WCFMOGCTVPWEFW-UHFFFAOYSA-N 0.000 description 3
- SKHXZXPLJNYYIU-UHFFFAOYSA-N ethyl 4-chloro-6,7-difluoro-2-methylquinoline-3-carboxylate Chemical compound C1=C(F)C(F)=CC2=C(Cl)C(C(=O)OCC)=C(C)N=C21 SKHXZXPLJNYYIU-UHFFFAOYSA-N 0.000 description 3
- DHCMYUJDUZOCAP-UHFFFAOYSA-N ethyl 4-chloro-6-fluoro-8-nitroquinoline-3-carboxylate Chemical compound [O-][N+](=O)C1=CC(F)=CC2=C(Cl)C(C(=O)OCC)=CN=C21 DHCMYUJDUZOCAP-UHFFFAOYSA-N 0.000 description 3
- LGNVXZKVUOHHDW-UHFFFAOYSA-N ethyl 4-chloro-8-fluoro-2-(trifluoromethyl)quinoline-3-carboxylate Chemical compound C1=CC(F)=C2N=C(C(F)(F)F)C(C(=O)OCC)=C(Cl)C2=C1 LGNVXZKVUOHHDW-UHFFFAOYSA-N 0.000 description 3
- HKWYTISEXCHKHX-UHFFFAOYSA-N ethyl 6,7-difluoro-2-methyl-4-oxo-1h-quinoline-3-carboxylate Chemical compound C1=C(F)C(F)=CC2=C(O)C(C(=O)OCC)=C(C)N=C21 HKWYTISEXCHKHX-UHFFFAOYSA-N 0.000 description 3
- NNLQZIMIZSCEIX-UHFFFAOYSA-N ethyl 6-fluoro-8-nitro-4-oxo-1h-quinoline-3-carboxylate Chemical compound [O-][N+](=O)C1=CC(F)=CC2=C(O)C(C(=O)OCC)=CN=C21 NNLQZIMIZSCEIX-UHFFFAOYSA-N 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 210000001320 hippocampus Anatomy 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 208000027061 mild cognitive impairment Diseases 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 230000010412 perfusion Effects 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 210000002442 prefrontal cortex Anatomy 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- 230000003936 working memory Effects 0.000 description 3
- PENWGQNPFRRVQI-UHFFFAOYSA-N (2-fluorophenyl)hydrazine Chemical compound NNC1=CC=CC=C1F PENWGQNPFRRVQI-UHFFFAOYSA-N 0.000 description 2
- PLNVOLRHQKALDD-UHFFFAOYSA-N 1,2,4-trifluoropyrazol-3-one Chemical compound FC=1C(N(N(C=1)F)F)=O PLNVOLRHQKALDD-UHFFFAOYSA-N 0.000 description 2
- DHZVSVIRHWJAFB-UHFFFAOYSA-N 1,8-difluoro-3,1-benzoxazine-2,4-dione Chemical compound FN1C(=O)OC(=O)C2=C1C(F)=CC=C2 DHZVSVIRHWJAFB-UHFFFAOYSA-N 0.000 description 2
- HNVIQLPOGUDBSU-UHFFFAOYSA-N 2,6-dimethylmorpholine Chemical compound CC1CNCC(C)O1 HNVIQLPOGUDBSU-UHFFFAOYSA-N 0.000 description 2
- IHNINSVQYKIZIC-UHFFFAOYSA-N 2h-quinolin-3-one Chemical compound C1=CC=CC2=CC(=O)CN=C21 IHNINSVQYKIZIC-UHFFFAOYSA-N 0.000 description 2
- JJHSCROEVPQTHA-UHFFFAOYSA-N 3-chloro-4,5-difluoro-2-methylquinoline Chemical compound C1=CC(F)=C2C(F)=C(Cl)C(C)=NC2=C1 JJHSCROEVPQTHA-UHFFFAOYSA-N 0.000 description 2
- XJCVRTZCHMZPBD-UHFFFAOYSA-N 3-nitroaniline Chemical compound NC1=CC=CC([N+]([O-])=O)=C1 XJCVRTZCHMZPBD-UHFFFAOYSA-N 0.000 description 2
- XXNOGQJZAOXWAQ-UHFFFAOYSA-N 4-chlorophenylhydrazine Chemical compound NNC1=CC=C(Cl)C=C1 XXNOGQJZAOXWAQ-UHFFFAOYSA-N 0.000 description 2
- FNLJHWKNAJQROC-UHFFFAOYSA-N 6-fluoro-7-piperazin-1-ylpyrazolo[3,4-h]quinoline Chemical compound C1=2C(F)=CC3=CC=CN=C3C=2C=NN1N1CCNCC1 FNLJHWKNAJQROC-UHFFFAOYSA-N 0.000 description 2
- NSJCYGJICSLDHJ-UHFFFAOYSA-N 6-piperazin-1-yl-8-(trifluoromethyl)pyrazolo[3,4-h]quinoline Chemical compound N=1N(C(F)(F)F)C=C(C2=NC=CC=C2C=2)C=1C=2N1CCNCC1 NSJCYGJICSLDHJ-UHFFFAOYSA-N 0.000 description 2
- NHTPIEGXARHRHE-UHFFFAOYSA-N 8-fluoro-2-phenyl-1h-pyrazolo[4,3-c]quinolin-3-one Chemical compound C12=CC(F)=CC=C2N=CC(C2=O)=C1NN2C1=CC=CC=C1 NHTPIEGXARHRHE-UHFFFAOYSA-N 0.000 description 2
- CDICAUPREKRESH-UHFFFAOYSA-N 8-fluoro-4-methyl-7-piperazin-1-yl-9h-pyrazolo[3,4-h]quinoline Chemical compound C12=CC=C3C(C)=CC=NC3=C2CN(F)N1N1CCNCC1 CDICAUPREKRESH-UHFFFAOYSA-N 0.000 description 2
- URKDOLAIKQOMOQ-UHFFFAOYSA-N 8-fluoro-7-piperazin-1-yl-1-thiophen-3-yl-4,5-dihydro-2H-pyrazolo[4,3-c]quinolin-3-one Chemical compound FC1=CC=2C3=C(CNC=2C=C1N1CCNCC1)C(NN3C1=CSC=C1)=O URKDOLAIKQOMOQ-UHFFFAOYSA-N 0.000 description 2
- TZFVXAFDZXVKTB-UHFFFAOYSA-N 8-piperidin-1-ylpyrazolo[3,4-h]quinoline Chemical compound C1CCCCN1N1N=C(C=CC=2C3=NC=CC=2)C3=C1 TZFVXAFDZXVKTB-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000167854 Bourreria succulenta Species 0.000 description 2
- GAJIKMYXJNGVPR-UHFFFAOYSA-N C12=CC(F)=CC=C2NC=C(C2=O)C1=NN2C1=CC=CC=C1F Chemical compound C12=CC(F)=CC=C2NC=C(C2=O)C1=NN2C1=CC=CC=C1F GAJIKMYXJNGVPR-UHFFFAOYSA-N 0.000 description 2
- BWXMQPJAAJNMHE-UHFFFAOYSA-N C12=CC([N+](=O)[O-])=CC=C2NC=C(C2=O)C1=NN2C1=CC=C(Cl)C=C1 Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC=C(C2=O)C1=NN2C1=CC=C(Cl)C=C1 BWXMQPJAAJNMHE-UHFFFAOYSA-N 0.000 description 2
- BIZSWIGIXXVNQU-UHFFFAOYSA-N C12=CC([N+](=O)[O-])=CC=C2NC=C(C2=O)C1=NN2C1=CC=CC=C1 Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC=C(C2=O)C1=NN2C1=CC=CC=C1 BIZSWIGIXXVNQU-UHFFFAOYSA-N 0.000 description 2
- GDNSUKUOEWBBQG-UHFFFAOYSA-N C1=2C=C(F)C(F)=CC=2NC=C(C2=O)C1=NN2C1=CC=CC=C1 Chemical compound C1=2C=C(F)C(F)=CC=2NC=C(C2=O)C1=NN2C1=CC=CC=C1 GDNSUKUOEWBBQG-UHFFFAOYSA-N 0.000 description 2
- KGHZDQBEVWKNJS-UHFFFAOYSA-N C1=2C=C(F)C(F)=CC=2NC=C(C2=O)C1=NN2C1=CC=CC=C1F Chemical compound C1=2C=C(F)C(F)=CC=2NC=C(C2=O)C1=NN2C1=CC=CC=C1F KGHZDQBEVWKNJS-UHFFFAOYSA-N 0.000 description 2
- ASQWVKDOVRJUOT-UHFFFAOYSA-N C1=2C=C(F)C(F)=CC=2NC=C(C2=O)C1=NN2C=1C=CSC=1 Chemical compound C1=2C=C(F)C(F)=CC=2NC=C(C2=O)C1=NN2C=1C=CSC=1 ASQWVKDOVRJUOT-UHFFFAOYSA-N 0.000 description 2
- YTDIDNNIRBRTMK-UHFFFAOYSA-N C1=2C=C(N3CCNCC3)C(Cl)=CC=2NC=C(C2=O)C1=NN2C1=CC=CC=C1 Chemical compound C1=2C=C(N3CCNCC3)C(Cl)=CC=2NC=C(C2=O)C1=NN2C1=CC=CC=C1 YTDIDNNIRBRTMK-UHFFFAOYSA-N 0.000 description 2
- PSLYFVGBRYHTIF-UHFFFAOYSA-N C1=2C=C(N3CCOCC3)C(Cl)=CC=2NC=C(C2=O)C1=NN2C1=CC=CC=C1 Chemical compound C1=2C=C(N3CCOCC3)C(Cl)=CC=2NC=C(C2=O)C1=NN2C1=CC=CC=C1 PSLYFVGBRYHTIF-UHFFFAOYSA-N 0.000 description 2
- WYIGLOCVMBZSOJ-UHFFFAOYSA-N C1=2C=C(N3CCOCC3)C(F)=CC=2NC=C(C2=O)C1=NN2C1=CC=CC=C1 Chemical compound C1=2C=C(N3CCOCC3)C(F)=CC=2NC=C(C2=O)C1=NN2C1=CC=CC=C1 WYIGLOCVMBZSOJ-UHFFFAOYSA-N 0.000 description 2
- UOSHELOWMFGSPB-UHFFFAOYSA-N C1=CC(Cl)=CC=C1N1C(=O)C2=CNC3=CC=C(N4CCNCC4)C=C3C2=N1 Chemical compound C1=CC(Cl)=CC=C1N1C(=O)C2=CNC3=CC=C(N4CCNCC4)C=C3C2=N1 UOSHELOWMFGSPB-UHFFFAOYSA-N 0.000 description 2
- XHAXELWINRRUCB-UHFFFAOYSA-N C1=CC(OC)=CC=C1N1C(=O)C2=CNC3=C(F)C(F)=C(F)C=C3C2=N1 Chemical compound C1=CC(OC)=CC=C1N1C(=O)C2=CNC3=C(F)C(F)=C(F)C=C3C2=N1 XHAXELWINRRUCB-UHFFFAOYSA-N 0.000 description 2
- WJWRHBKTYSQJTE-UHFFFAOYSA-N C1=CC(OC)=CC=C1N1C(=O)C2=CNC3=C(F)C(N4CCN(C)CC4)=C(F)C=C3C2=N1 Chemical compound C1=CC(OC)=CC=C1N1C(=O)C2=CNC3=C(F)C(N4CCN(C)CC4)=C(F)C=C3C2=N1 WJWRHBKTYSQJTE-UHFFFAOYSA-N 0.000 description 2
- MPYSRWDEFAWVFC-UHFFFAOYSA-N C1=CC(OC)=CC=C1N1C(=O)C2=CNC3=CC(N)=CC=C3C2=N1 Chemical compound C1=CC(OC)=CC=C1N1C(=O)C2=CNC3=CC(N)=CC=C3C2=N1 MPYSRWDEFAWVFC-UHFFFAOYSA-N 0.000 description 2
- HMIIVMFVHZUAMI-UHFFFAOYSA-N C1=CC(OC)=CC=C1N1C(=O)C2=CNC3=CC(N4CCN(C)CC4)=CC=C3C2=N1 Chemical compound C1=CC(OC)=CC=C1N1C(=O)C2=CNC3=CC(N4CCN(C)CC4)=CC=C3C2=N1 HMIIVMFVHZUAMI-UHFFFAOYSA-N 0.000 description 2
- AYGUSHBSGSAFIZ-UHFFFAOYSA-N C1=CC(OC)=CC=C1N1C(=O)C2=CNC3=CC([N+]([O-])=O)=CC=C3C2=N1 Chemical compound C1=CC(OC)=CC=C1N1C(=O)C2=CNC3=CC([N+]([O-])=O)=CC=C3C2=N1 AYGUSHBSGSAFIZ-UHFFFAOYSA-N 0.000 description 2
- YTTOUVSBLOFTDP-UHFFFAOYSA-N C1=CC(OC)=CC=C1N1C(=O)C2=CNC3=CC=C(F)C=C3C2=N1 Chemical compound C1=CC(OC)=CC=C1N1C(=O)C2=CNC3=CC=C(F)C=C3C2=N1 YTTOUVSBLOFTDP-UHFFFAOYSA-N 0.000 description 2
- HTXBULFMOVCMQS-UHFFFAOYSA-N C1=CC(OC)=CC=C1N1C(=O)C2=CNC3=CC=C(N4CCN(C)CC4)C=C3C2=N1 Chemical compound C1=CC(OC)=CC=C1N1C(=O)C2=CNC3=CC=C(N4CCN(C)CC4)C=C3C2=N1 HTXBULFMOVCMQS-UHFFFAOYSA-N 0.000 description 2
- KBDCJNLJCATUCF-UHFFFAOYSA-N C1=CC(OC)=CC=C1N1C(=O)C2=CNC3=CC=C(N4CCNCC4)C=C3C2=N1 Chemical compound C1=CC(OC)=CC=C1N1C(=O)C2=CNC3=CC=C(N4CCNCC4)C=C3C2=N1 KBDCJNLJCATUCF-UHFFFAOYSA-N 0.000 description 2
- NSWJSCWPBVEMPJ-UHFFFAOYSA-N C1C(C)CC(C)CN1C(C(=C1)F)=CC(NC=C2C3=O)=C1C2=NN3C1=CC=CC=C1 Chemical compound C1C(C)CC(C)CN1C(C(=C1)F)=CC(NC=C2C3=O)=C1C2=NN3C1=CC=CC=C1 NSWJSCWPBVEMPJ-UHFFFAOYSA-N 0.000 description 2
- WQARGJZPXCIJRV-UHFFFAOYSA-N C1C(C)OC(C)CN1C1=CC=C(NC=C2C(N(C=3C=CC=CC=3)N=C22)=O)C2=C1 Chemical compound C1C(C)OC(C)CN1C1=CC=C(NC=C2C(N(C=3C=CC=CC=3)N=C22)=O)C2=C1 WQARGJZPXCIJRV-UHFFFAOYSA-N 0.000 description 2
- NOXPEPXRDPRYJI-UHFFFAOYSA-N C1CC(O)CCN1C(C(=C1)F)=CC(NC=C2C3=O)=C1C2=NN3C1=CC=CC=C1 Chemical compound C1CC(O)CCN1C(C(=C1)F)=CC(NC=C2C3=O)=C1C2=NN3C1=CC=CC=C1 NOXPEPXRDPRYJI-UHFFFAOYSA-N 0.000 description 2
- KOQDFYZGCOAVSI-UHFFFAOYSA-N C1CN(C(C)C)CCN1C(C(=C1)F)=CC(NC=C2C3=O)=C1C2=NN3C1=CC=CC=C1 Chemical compound C1CN(C(C)C)CCN1C(C(=C1)F)=CC(NC=C2C3=O)=C1C2=NN3C1=CC=CC=C1 KOQDFYZGCOAVSI-UHFFFAOYSA-N 0.000 description 2
- RDHPPGKOQFVGDT-UHFFFAOYSA-N C1CN(C(C)C)CCN1C1=CC(C(F)(F)F)=CC2=C1NC=C1C(=O)N(C=3C=CC=CC=3)N=C12 Chemical compound C1CN(C(C)C)CCN1C1=CC(C(F)(F)F)=CC2=C1NC=C1C(=O)N(C=3C=CC=CC=3)N=C12 RDHPPGKOQFVGDT-UHFFFAOYSA-N 0.000 description 2
- XQWYLBAUEIYCDJ-UHFFFAOYSA-N C1CN(C(C)C)CCN1C1=CC=C(C=2C(C(=O)N(C=3C=CC=CC=3)N=2)=CN2)C2=C1F Chemical compound C1CN(C(C)C)CCN1C1=CC=C(C=2C(C(=O)N(C=3C=CC=CC=3)N=2)=CN2)C2=C1F XQWYLBAUEIYCDJ-UHFFFAOYSA-N 0.000 description 2
- CRRZZLCGJHCZKY-UHFFFAOYSA-N C1CN(C(C)C)CCN1C1=CC=C(NC=C2C(N(C=3C=CC=CC=3)N=C22)=O)C2=C1 Chemical compound C1CN(C(C)C)CCN1C1=CC=C(NC=C2C(N(C=3C=CC=CC=3)N=C22)=O)C2=C1 CRRZZLCGJHCZKY-UHFFFAOYSA-N 0.000 description 2
- LRLNDLPYLHXYJV-UHFFFAOYSA-N C1CN(C)CCN1C(C(=C1)F)=CC(NC=C2C3=O)=C1C2=NN3C1=CC=CC=C1F Chemical compound C1CN(C)CCN1C(C(=C1)F)=CC(NC=C2C3=O)=C1C2=NN3C1=CC=CC=C1F LRLNDLPYLHXYJV-UHFFFAOYSA-N 0.000 description 2
- DDJCULHBYCXZLG-UHFFFAOYSA-N C1CN(C)CCN1C(C(=C1)F)=CC(NC=C2C3=O)=C1C2=NN3C1=CC=CC=N1 Chemical compound C1CN(C)CCN1C(C(=C1)F)=CC(NC=C2C3=O)=C1C2=NN3C1=CC=CC=N1 DDJCULHBYCXZLG-UHFFFAOYSA-N 0.000 description 2
- OTMWHDUGUSKPNH-UHFFFAOYSA-N C1CN(C)CCN1C(C(=C1)F)=CC(NC=C2C3=O)=C1C2=NN3C1=CSC=C1 Chemical compound C1CN(C)CCN1C(C(=C1)F)=CC(NC=C2C3=O)=C1C2=NN3C1=CSC=C1 OTMWHDUGUSKPNH-UHFFFAOYSA-N 0.000 description 2
- WBCVSGIIHRWYCS-UHFFFAOYSA-N C1CN(C)CCN1C1=CC(C(F)(F)F)=CC2=C1NC=C1C(=O)N(C=3C=CC=CC=3)N=C12 Chemical compound C1CN(C)CCN1C1=CC(C(F)(F)F)=CC2=C1NC=C1C(=O)N(C=3C=CC=CC=3)N=C12 WBCVSGIIHRWYCS-UHFFFAOYSA-N 0.000 description 2
- LYIJWAKEBJLZRF-UHFFFAOYSA-N C1CN(C)CCN1C1=CC=C(C=2C(C(=O)N(C=3C=CC(Cl)=CC=3)N=2)=CN2)C2=C1 Chemical compound C1CN(C)CCN1C1=CC=C(C=2C(C(=O)N(C=3C=CC(Cl)=CC=3)N=2)=CN2)C2=C1 LYIJWAKEBJLZRF-UHFFFAOYSA-N 0.000 description 2
- CCHSPQMEIVDPHY-UHFFFAOYSA-N C1CN(C)CCN1C1=CC=C(C=2C(C(=O)N(C=3C=CC=CC=3)N=2)=CN2)C2=C1 Chemical compound C1CN(C)CCN1C1=CC=C(C=2C(C(=O)N(C=3C=CC=CC=3)N=2)=CN2)C2=C1 CCHSPQMEIVDPHY-UHFFFAOYSA-N 0.000 description 2
- NFJDGYGBPKVRAI-UHFFFAOYSA-N C1CN(C)CCN1C1=CC=C(C=2C(C(=O)N(C=3C=CC=CC=3)N=2)=CN2)C2=C1F Chemical compound C1CN(C)CCN1C1=CC=C(C=2C(C(=O)N(C=3C=CC=CC=3)N=2)=CN2)C2=C1F NFJDGYGBPKVRAI-UHFFFAOYSA-N 0.000 description 2
- MRLOVZKAPMEBBK-UHFFFAOYSA-N C1CN(C)CCN1C1=CC=C(NC=C2C(N(C=3C=CC(Cl)=CC=3)N=C22)=O)C2=C1 Chemical compound C1CN(C)CCN1C1=CC=C(NC=C2C(N(C=3C=CC(Cl)=CC=3)N=C22)=O)C2=C1 MRLOVZKAPMEBBK-UHFFFAOYSA-N 0.000 description 2
- ZJZLKGGDUQMTJQ-UHFFFAOYSA-N C1CN(C)CCN1C1=CC=C(NC=C2C(N(C=3C=CC=CC=3)N=C22)=O)C2=C1 Chemical compound C1CN(C)CCN1C1=CC=C(NC=C2C(N(C=3C=CC=CC=3)N=C22)=O)C2=C1 ZJZLKGGDUQMTJQ-UHFFFAOYSA-N 0.000 description 2
- DATLSQPORJEJPN-UHFFFAOYSA-N C1CN(CCOC)CCN1C1=CC=C(NC=C2C(N(C=3C=CC=CC=3)N=C22)=O)C2=C1 Chemical compound C1CN(CCOC)CCN1C1=CC=C(NC=C2C(N(C=3C=CC=CC=3)N=C22)=O)C2=C1 DATLSQPORJEJPN-UHFFFAOYSA-N 0.000 description 2
- MVMDTHCXOKMHDG-UHFFFAOYSA-N C=12NC=C(C(N(C=3C=CC=CC=3)N=3)=O)C=3C2=CC(C(F)(F)F)=CC=1N1CCCNCC1 Chemical compound C=12NC=C(C(N(C=3C=CC=CC=3)N=3)=O)C=3C2=CC(C(F)(F)F)=CC=1N1CCCNCC1 MVMDTHCXOKMHDG-UHFFFAOYSA-N 0.000 description 2
- YUSLORFNAYHIQK-UHFFFAOYSA-N C=12NC=C(C(N(C=3C=CC=CC=3)N=3)=O)C=3C2=CC(C(F)(F)F)=CC=1N1CCNCC1 Chemical compound C=12NC=C(C(N(C=3C=CC=CC=3)N=3)=O)C=3C2=CC(C(F)(F)F)=CC=1N1CCNCC1 YUSLORFNAYHIQK-UHFFFAOYSA-N 0.000 description 2
- 208000022540 Consciousness disease Diseases 0.000 description 2
- 206010010904 Convulsion Diseases 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 206010012289 Dementia Diseases 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- ANOGRHJHNBOSND-UHFFFAOYSA-N FC1=CC=CC=C1N1C(=O)C2=CNC3=CC(N4CCNCC4)=C(F)C=C3C2=N1 Chemical compound FC1=CC=CC=C1N1C(=O)C2=CNC3=CC(N4CCNCC4)=C(F)C=C3C2=N1 ANOGRHJHNBOSND-UHFFFAOYSA-N 0.000 description 2
- XYIWIDLSJLTKSS-UHFFFAOYSA-N FC1=CC=CC=C1N1C(=O)C2=CNC3=CC=C(N4CCOCC4)C=C3C2=N1 Chemical compound FC1=CC=CC=C1N1C(=O)C2=CNC3=CC=C(N4CCOCC4)C=C3C2=N1 XYIWIDLSJLTKSS-UHFFFAOYSA-N 0.000 description 2
- VWPOUJRRGMDNKS-UHFFFAOYSA-N FC=1C=C2C3=NN(C=4C=CC=CC=4)C(=O)C3=C(C)NC2=CC=1N1CCNCC1 Chemical compound FC=1C=C2C3=NN(C=4C=CC=CC=4)C(=O)C3=C(C)NC2=CC=1N1CCNCC1 VWPOUJRRGMDNKS-UHFFFAOYSA-N 0.000 description 2
- IEGAGPQTKYMGQJ-UHFFFAOYSA-N FC=1C=C2C3=NN(C=4C=CC=CC=4)C(=O)C3=C(C)NC2=CC=1N1CCOCC1 Chemical compound FC=1C=C2C3=NN(C=4C=CC=CC=4)C(=O)C3=C(C)NC2=CC=1N1CCOCC1 IEGAGPQTKYMGQJ-UHFFFAOYSA-N 0.000 description 2
- 229930091371 Fructose Natural products 0.000 description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
- 239000005715 Fructose Substances 0.000 description 2
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 2
- 229930182566 Gentamicin Natural products 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- FNGAHDWZBLUDPW-UHFFFAOYSA-N N1=CC=CC2=CC=CC=C12.FC=1C(N(N(C1)F)F)=O Chemical compound N1=CC=CC2=CC=CC=C12.FC=1C(N(N(C1)F)F)=O FNGAHDWZBLUDPW-UHFFFAOYSA-N 0.000 description 2
- 229910002651 NO3 Inorganic materials 0.000 description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical class [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
- AOVIFKBOSUGXKZ-UHFFFAOYSA-N O=C1C2=CNC3=C(F)C(F)=CC=C3C2=NN1C1=CC=CC=N1 Chemical compound O=C1C2=CNC3=C(F)C(F)=CC=C3C2=NN1C1=CC=CC=N1 AOVIFKBOSUGXKZ-UHFFFAOYSA-N 0.000 description 2
- KNTOPQUZZHDYCM-UHFFFAOYSA-N O=C1C2=CNC3=CC(N)=CC=C3C2=NN1C1=CC=C(Cl)C=C1 Chemical compound O=C1C2=CNC3=CC(N)=CC=C3C2=NN1C1=CC=C(Cl)C=C1 KNTOPQUZZHDYCM-UHFFFAOYSA-N 0.000 description 2
- DUEYYBLKBQLGSG-UHFFFAOYSA-N O=C1C2=CNC3=CC(N)=CC=C3C2=NN1C1=CC=CC=C1 Chemical compound O=C1C2=CNC3=CC(N)=CC=C3C2=NN1C1=CC=CC=C1 DUEYYBLKBQLGSG-UHFFFAOYSA-N 0.000 description 2
- GSOGJWIAXZDGGO-UHFFFAOYSA-N O=C1C2=CNC3=CC([N+](=O)[O-])=CC=C3C2=NN1C1=CC=C(Cl)C=C1 Chemical compound O=C1C2=CNC3=CC([N+](=O)[O-])=CC=C3C2=NN1C1=CC=C(Cl)C=C1 GSOGJWIAXZDGGO-UHFFFAOYSA-N 0.000 description 2
- ZZQOXMMLBWQAAA-UHFFFAOYSA-N O=C1C2=CNC3=CC([N+](=O)[O-])=CC=C3C2=NN1C1=CC=CC=C1 Chemical compound O=C1C2=CNC3=CC([N+](=O)[O-])=CC=C3C2=NN1C1=CC=CC=C1 ZZQOXMMLBWQAAA-UHFFFAOYSA-N 0.000 description 2
- WHAPDUAQGRGYCY-UHFFFAOYSA-N O=C1C2=CNC=3C(F)=C(F)C(F)=CC=3C2=NN1C1=CC=CC=C1 Chemical compound O=C1C2=CNC=3C(F)=C(F)C(F)=CC=3C2=NN1C1=CC=CC=C1 WHAPDUAQGRGYCY-UHFFFAOYSA-N 0.000 description 2
- RFGWQYMMBOORKX-UHFFFAOYSA-N O=C1C2=CNC=3C(F)=C(N4CCNCC4)C(F)=CC=3C2=NN1C1=CC=CC=C1 Chemical compound O=C1C2=CNC=3C(F)=C(N4CCNCC4)C(F)=CC=3C2=NN1C1=CC=CC=C1 RFGWQYMMBOORKX-UHFFFAOYSA-N 0.000 description 2
- UQSGFMMNHCMLSW-UHFFFAOYSA-N O=C1C2=CNC=3C(F)=C(N4CCNCC4)C=CC=3C2=NN1C1=CC=CC=C1 Chemical compound O=C1C2=CNC=3C(F)=C(N4CCNCC4)C=CC=3C2=NN1C1=CC=CC=C1 UQSGFMMNHCMLSW-UHFFFAOYSA-N 0.000 description 2
- UKTOLZNEMRJAJG-UHFFFAOYSA-N O=C1C2=CNC=3C(F)=C(N4CCNCCC4)C=CC=3C2=NN1C1=CC=CC=C1 Chemical compound O=C1C2=CNC=3C(F)=C(N4CCNCCC4)C=CC=3C2=NN1C1=CC=CC=C1 UKTOLZNEMRJAJG-UHFFFAOYSA-N 0.000 description 2
- JNQQVGUCJNEIBD-UHFFFAOYSA-N O=C1C2=CNC=3C(F)=C(N4CCOCC4)C(F)=CC=3C2=NN1C1=CC=CC=C1 Chemical compound O=C1C2=CNC=3C(F)=C(N4CCOCC4)C(F)=CC=3C2=NN1C1=CC=CC=C1 JNQQVGUCJNEIBD-UHFFFAOYSA-N 0.000 description 2
- HEFXBNIIJGBFTB-UHFFFAOYSA-N O=C1C2=CNC=3C(F)=C(N4CCOCC4)C=CC=3C2=NN1C1=CC=CC=C1 Chemical compound O=C1C2=CNC=3C(F)=C(N4CCOCC4)C=CC=3C2=NN1C1=CC=CC=C1 HEFXBNIIJGBFTB-UHFFFAOYSA-N 0.000 description 2
- AYNANGNRVAGASK-UHFFFAOYSA-N O=C1C2=CNC=3C=C(Cl)C(F)=CC=3C2=NN1C1=CC=CC=C1 Chemical compound O=C1C2=CNC=3C=C(Cl)C(F)=CC=3C2=NN1C1=CC=CC=C1 AYNANGNRVAGASK-UHFFFAOYSA-N 0.000 description 2
- HVIRQKRIWIBURO-UHFFFAOYSA-N O=C1C2=CNC=3C=C(N4CCN(CC4)C4CCCC4)C(F)=CC=3C2=NN1C1=CC=CC=C1 Chemical compound O=C1C2=CNC=3C=C(N4CCN(CC4)C4CCCC4)C(F)=CC=3C2=NN1C1=CC=CC=C1 HVIRQKRIWIBURO-UHFFFAOYSA-N 0.000 description 2
- YMRSVVBORFHKIR-UHFFFAOYSA-N O=C1C2=CNC=3C=C(N4CCNCC4)C(F)=CC=3C2=NN1C1=CC=CC=C1 Chemical compound O=C1C2=CNC=3C=C(N4CCNCC4)C(F)=CC=3C2=NN1C1=CC=CC=C1 YMRSVVBORFHKIR-UHFFFAOYSA-N 0.000 description 2
- QOLJGUPEABLPMZ-UHFFFAOYSA-N O=C1C2=CNC=3C=C(N4CCOCC4)C(F)=CC=3C2=NN1C1=CC=CC=C1 Chemical compound O=C1C2=CNC=3C=C(N4CCOCC4)C(F)=CC=3C2=NN1C1=CC=CC=C1 QOLJGUPEABLPMZ-UHFFFAOYSA-N 0.000 description 2
- XMNVRDYKTJDBSI-UHFFFAOYSA-N O=C1C2=CNC=3C=C(N4CCOCC4)C(F)=CC=3C2=NN1C1=CC=CC=N1 Chemical compound O=C1C2=CNC=3C=C(N4CCOCC4)C(F)=CC=3C2=NN1C1=CC=CC=N1 XMNVRDYKTJDBSI-UHFFFAOYSA-N 0.000 description 2
- CGIFMHOIFAXWTC-UHFFFAOYSA-N O=C1C2=CNC=3C=C(N4CCOCC4)C(F)=CC=3C2=NN1C=1C=CSC=1 Chemical compound O=C1C2=CNC=3C=C(N4CCOCC4)C(F)=CC=3C2=NN1C=1C=CSC=1 CGIFMHOIFAXWTC-UHFFFAOYSA-N 0.000 description 2
- WKJMDEWEZJFION-UHFFFAOYSA-N O=C1N(C=2C=CC=CC=2)N=C(C2=C3)C1=CNC2=C(N1CCOCC1)C=C3N1CCOCC1 Chemical compound O=C1N(C=2C=CC=CC=2)N=C(C2=C3)C1=CNC2=C(N1CCOCC1)C=C3N1CCOCC1 WKJMDEWEZJFION-UHFFFAOYSA-N 0.000 description 2
- SKLQAKLGLNAUGA-UHFFFAOYSA-N O=C1N(C=2C=CC=CC=2)N=C(C2=C3)C1=CNC2=CC=C3N1CCNCC1 Chemical compound O=C1N(C=2C=CC=CC=2)N=C(C2=C3)C1=CNC2=CC=C3N1CCNCC1 SKLQAKLGLNAUGA-UHFFFAOYSA-N 0.000 description 2
- HXPHSIBTUIYJPQ-UHFFFAOYSA-N O=C1N(C=2C=CC=CC=2)N=C(C2=C3)C1=CNC2=CC=C3N1CCOCC1 Chemical compound O=C1N(C=2C=CC=CC=2)N=C(C2=C3)C1=CNC2=CC=C3N1CCOCC1 HXPHSIBTUIYJPQ-UHFFFAOYSA-N 0.000 description 2
- SZSCRROKODAZJB-UHFFFAOYSA-N O=C1N(C=2C=CC=CC=2)N=C(C2=CC=3)C1=CNC2=CC=3N1CCNCC1 Chemical compound O=C1N(C=2C=CC=CC=2)N=C(C2=CC=3)C1=CNC2=CC=3N1CCNCC1 SZSCRROKODAZJB-UHFFFAOYSA-N 0.000 description 2
- GTVJPOBUZDPSFO-UHFFFAOYSA-N O=C1N(C=2C=CC=CC=2)N=C(C2=CC=3)C1=CNC2=CC=3N1CCOCC1 Chemical compound O=C1N(C=2C=CC=CC=2)N=C(C2=CC=3)C1=CNC2=CC=3N1CCOCC1 GTVJPOBUZDPSFO-UHFFFAOYSA-N 0.000 description 2
- IUBWEKGXCVADPJ-UHFFFAOYSA-N O=C1N(C=2N=CC=CC=2)N=C(C2=C3)C1=CNC2=CC=C3N1CCOCC1 Chemical compound O=C1N(C=2N=CC=CC=2)N=C(C2=C3)C1=CNC2=CC=C3N1CCOCC1 IUBWEKGXCVADPJ-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 229920005372 Plexiglas® Polymers 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 2
- PPTYJKAXVCCBDU-UHFFFAOYSA-N Rohypnol Chemical compound N=1CC(=O)N(C)C2=CC=C([N+]([O-])=O)C=C2C=1C1=CC=CC=C1F PPTYJKAXVCCBDU-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 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 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 241000269370 Xenopus <genus> Species 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 150000001345 alkine derivatives Chemical group 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 235000010290 biphenyl Nutrition 0.000 description 2
- 239000004305 biphenyl Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 125000001589 carboacyl group Chemical group 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 208000015114 central nervous system disease Diseases 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 235000019693 cherries Nutrition 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 230000019771 cognition Effects 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 2
- 229960003529 diazepam Drugs 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- PPHSOQWURBALSQ-UHFFFAOYSA-N ethyl 4-chloro-6-fluoroquinoline-3-carboxylate Chemical compound C1=CC(F)=CC2=C(Cl)C(C(=O)OCC)=CN=C21 PPHSOQWURBALSQ-UHFFFAOYSA-N 0.000 description 2
- HBCNNYCEPZHQRC-UHFFFAOYSA-N ethyl 4-chloro-7-fluoro-6-morpholin-4-ylquinoline-3-carboxylate Chemical compound C=1C2=C(Cl)C(C(=O)OCC)=CN=C2C=C(F)C=1N1CCOCC1 HBCNNYCEPZHQRC-UHFFFAOYSA-N 0.000 description 2
- ICWBNSHNWYOKSJ-UHFFFAOYSA-N ethyl 4-chloro-7-nitroquinoline-3-carboxylate Chemical compound C1=C([N+]([O-])=O)C=CC2=C(Cl)C(C(=O)OCC)=CN=C21 ICWBNSHNWYOKSJ-UHFFFAOYSA-N 0.000 description 2
- LNPRCADPRULVTR-UHFFFAOYSA-N ethyl 6-fluoro-4-oxo-1h-quinoline-3-carboxylate Chemical compound C1=C(F)C=C2C(=O)C(C(=O)OCC)=CNC2=C1 LNPRCADPRULVTR-UHFFFAOYSA-N 0.000 description 2
- DBJCDCSZGDONQQ-UHFFFAOYSA-N ethyl 6-nitro-4-oxo-1h-quinoline-3-carboxylate Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)C(C(=O)OCC)=CNC2=C1 DBJCDCSZGDONQQ-UHFFFAOYSA-N 0.000 description 2
- BIFIWEDEMMZFND-UHFFFAOYSA-N ethyl 7,8-difluoro-4-oxo-1h-quinoline-3-carboxylate Chemical compound FC1=C(F)C=CC2=C(O)C(C(=O)OCC)=CN=C21 BIFIWEDEMMZFND-UHFFFAOYSA-N 0.000 description 2
- LYNIYLCGKJWHSC-UHFFFAOYSA-N ethyl 7-nitro-4-oxo-1h-quinoline-3-carboxylate Chemical compound [O-][N+](=O)C1=CC=C2C(=O)C(C(=O)OCC)=CNC2=C1 LYNIYLCGKJWHSC-UHFFFAOYSA-N 0.000 description 2
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- 229960002518 gentamicin Drugs 0.000 description 2
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 2
- 239000002502 liposome 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
- 239000012528 membrane Substances 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000004926 polymethyl methacrylate Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 239000000932 sedative agent Substances 0.000 description 2
- 230000001624 sedative effect Effects 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- WHSJJNSDVXKXFY-UHFFFAOYSA-N 1-(1-methoxyethyl)piperazine Chemical compound COC(C)N1CCNCC1 WHSJJNSDVXKXFY-UHFFFAOYSA-N 0.000 description 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
- PVMCQBPJKPMOKM-UHFFFAOYSA-N 1-cyclopentylpiperazine Chemical compound C1CCCC1N1CCNCC1 PVMCQBPJKPMOKM-UHFFFAOYSA-N 0.000 description 1
- FXHRAKUEZPSMLJ-UHFFFAOYSA-N 1-methyl-1,4-diazepane Chemical compound CN1CCCNCC1 FXHRAKUEZPSMLJ-UHFFFAOYSA-N 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- CEPCPXLLFXPZGW-UHFFFAOYSA-N 2,4-difluoroaniline Chemical compound NC1=CC=C(F)C=C1F CEPCPXLLFXPZGW-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- PUVQHXRVPVCCHF-UHFFFAOYSA-N 2-chloro-3,4,5-trifluoroquinoline Chemical compound ClC1=C(F)C(F)=C2C(F)=CC=CC2=N1 PUVQHXRVPVCCHF-UHFFFAOYSA-N 0.000 description 1
- YMDZDFSUDFLGMX-UHFFFAOYSA-N 2-chloro-n-(2-chloroethyl)ethanamine;hydron;chloride Chemical compound [Cl-].ClCC[NH2+]CCCl YMDZDFSUDFLGMX-UHFFFAOYSA-N 0.000 description 1
- ARHDUOQIXLGANT-UHFFFAOYSA-N 2-fluoro-4-(trifluoromethyl)aniline Chemical compound NC1=CC=C(C(F)(F)F)C=C1F ARHDUOQIXLGANT-UHFFFAOYSA-N 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
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- 125000006020 2-methyl-1-propenyl group Chemical group 0.000 description 1
- DPJCXCZTLWNFOH-UHFFFAOYSA-N 2-nitroaniline Chemical compound NC1=CC=CC=C1[N+]([O-])=O DPJCXCZTLWNFOH-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- SZRDJHHKIJHJHQ-UHFFFAOYSA-N 3,4,5-trifluoroaniline Chemical compound NC1=CC(F)=C(F)C(F)=C1 SZRDJHHKIJHJHQ-UHFFFAOYSA-N 0.000 description 1
- SDNUSNYVSDILFK-UHFFFAOYSA-N 3,4-difluoro-1h-quinolin-2-one Chemical compound C1=CC=C2C(F)=C(F)C(=O)NC2=C1 SDNUSNYVSDILFK-UHFFFAOYSA-N 0.000 description 1
- AXNUZKSSQHTNPZ-UHFFFAOYSA-N 3,4-difluoroaniline Chemical compound NC1=CC=C(F)C(F)=C1 AXNUZKSSQHTNPZ-UHFFFAOYSA-N 0.000 description 1
- IDWRJRPUIXRFRX-UHFFFAOYSA-N 3,5-dimethylpiperidine Chemical compound CC1CNCC(C)C1 IDWRJRPUIXRFRX-UHFFFAOYSA-N 0.000 description 1
- FQGIBHQUVCGEAC-UHFFFAOYSA-N 3-Fluoro-4-morpholinoaniline Chemical compound FC1=CC(N)=CC=C1N1CCOCC1 FQGIBHQUVCGEAC-UHFFFAOYSA-N 0.000 description 1
- FRFSUUWVTVDAJG-UHFFFAOYSA-N 3-fluoro-1h-quinolin-2-one Chemical compound C1=CC=C2NC(=O)C(F)=CC2=C1 FRFSUUWVTVDAJG-UHFFFAOYSA-N 0.000 description 1
- HXYGAXGTROQSIP-UHFFFAOYSA-N 4-(8-fluoro-7-morpholin-4-yl-9h-pyrazolo[3,4-h]quinolin-9-yl)morpholine Chemical compound C1=CC2=CC=CN=C2C2=C1N(N1CCOCC1)N(F)C2N1CCOCC1 HXYGAXGTROQSIP-UHFFFAOYSA-N 0.000 description 1
- FLKFKUSJAFUYDU-UHFFFAOYSA-N 4-chloro-6-nitroquinoline Chemical compound N1=CC=C(Cl)C2=CC([N+](=O)[O-])=CC=C21 FLKFKUSJAFUYDU-UHFFFAOYSA-N 0.000 description 1
- PUGDHSSOXPHLPT-UHFFFAOYSA-N 4-fluoro-2-nitroaniline Chemical compound NC1=CC=C(F)C=C1[N+]([O-])=O PUGDHSSOXPHLPT-UHFFFAOYSA-N 0.000 description 1
- KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 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
- RCZMKFBXTLFVDD-UHFFFAOYSA-N 6,8-difluoro-7-piperazin-1-yl-9h-pyrazolo[3,4-h]quinoline Chemical compound FN1CC(C2=NC=CC=C2C=C2F)=C2N1N1CCNCC1 RCZMKFBXTLFVDD-UHFFFAOYSA-N 0.000 description 1
- MGCGVNRWZOHFTO-UHFFFAOYSA-N 6-nitro-1h-quinolin-4-one Chemical compound N1C=CC(=O)C2=CC([N+](=O)[O-])=CC=C21 MGCGVNRWZOHFTO-UHFFFAOYSA-N 0.000 description 1
- ORAQNDQJGOTAPI-UHFFFAOYSA-N 7-piperazin-1-ylpyrazolo[3,4-h]quinoline Chemical compound C1CNCCN1N1C(C=CC=2C3=NC=CC=2)=C3C=N1 ORAQNDQJGOTAPI-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- LHBADKHJGJOQIL-UHFFFAOYSA-N 8-piperazin-1-ylpyrazolo[3,4-h]quinoline Chemical compound C1CNCCN1N1N=C(C=CC=2C3=NC=CC=2)C3=C1 LHBADKHJGJOQIL-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 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
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- CNXZFZKGEAMLLS-UHFFFAOYSA-N C12=CC(N)=CC=C2NC=C(C2=O)C1=NN2C1=CC=C(Cl)C=C1 Chemical compound C12=CC(N)=CC=C2NC=C(C2=O)C1=NN2C1=CC=C(Cl)C=C1 CNXZFZKGEAMLLS-UHFFFAOYSA-N 0.000 description 1
- BTWMWCSZYHFOJF-UHFFFAOYSA-N C1=CC(OC)=CC=C1N1C(=O)C2=CNC3=CC(N4CCNCC4)=CC=C3C2=N1 Chemical compound C1=CC(OC)=CC=C1N1C(=O)C2=CNC3=CC(N4CCNCC4)=CC=C3C2=N1 BTWMWCSZYHFOJF-UHFFFAOYSA-N 0.000 description 1
- YAUVCCJTRNEZRM-UHFFFAOYSA-N C1=CC(OC)=CC=C1N1C(=O)C2=CNC3=CC=C(N)C=C3C2=N1 Chemical compound C1=CC(OC)=CC=C1N1C(=O)C2=CNC3=CC=C(N)C=C3C2=N1 YAUVCCJTRNEZRM-UHFFFAOYSA-N 0.000 description 1
- MADFSYKUJVXQBF-UHFFFAOYSA-N C1=CC(OC)=CC=C1N1C(=O)C2=CNC3=CC=C(N4CCN(CC4)C(C)C)C=C3C2=N1 Chemical compound C1=CC(OC)=CC=C1N1C(=O)C2=CNC3=CC=C(N4CCN(CC4)C(C)C)C=C3C2=N1 MADFSYKUJVXQBF-UHFFFAOYSA-N 0.000 description 1
- METBOXACNNZCBF-UHFFFAOYSA-N C1C(C)OC(C)CN1C(C(=C1)F)=CC(NC=C2C3=O)=C1C2=NN3C1=CC=CC=C1 Chemical compound C1C(C)OC(C)CN1C(C(=C1)F)=CC(NC=C2C3=O)=C1C2=NN3C1=CC=CC=C1 METBOXACNNZCBF-UHFFFAOYSA-N 0.000 description 1
- VWEYWIPWYADPGS-UHFFFAOYSA-N C1CC(N(C)C)CCN1C(C(=C1)F)=CC(NC=C2C3=O)=C1C2=NN3C1=CC=CC=C1 Chemical compound C1CC(N(C)C)CCN1C(C(=C1)F)=CC(NC=C2C3=O)=C1C2=NN3C1=CC=CC=C1 VWEYWIPWYADPGS-UHFFFAOYSA-N 0.000 description 1
- SJPQDINRODKTMN-UHFFFAOYSA-N C1CN(C)CCCN1C(C(=C1)F)=CC(NC=C2C3=O)=C1C2=NN3C1=CC=CC=C1 Chemical compound C1CN(C)CCCN1C(C(=C1)F)=CC(NC=C2C3=O)=C1C2=NN3C1=CC=CC=C1 SJPQDINRODKTMN-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical class [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 1
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 1
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 1
- 241000938605 Crocodylia Species 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
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 108010067770 Endopeptidase K Proteins 0.000 description 1
- 201000011240 Frontotemporal dementia Diseases 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 102000005915 GABA Receptors Human genes 0.000 description 1
- 108010005551 GABA Receptors Proteins 0.000 description 1
- 102000004300 GABA-A Receptors Human genes 0.000 description 1
- 108090000839 GABA-A Receptors Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 241001272567 Hominoidea Species 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 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 1
- 235000006679 Mentha X verticillata Nutrition 0.000 description 1
- 235000002899 Mentha suaveolens Nutrition 0.000 description 1
- 235000001636 Mentha x rotundifolia Nutrition 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- ZKGNPQKYVKXMGJ-UHFFFAOYSA-N N,N-dimethylacetamide Chemical compound CN(C)C(C)=O.CN(C)C(C)=O ZKGNPQKYVKXMGJ-UHFFFAOYSA-N 0.000 description 1
- CJRBZQVGAHWBFY-UHFFFAOYSA-N N1(CCOCC1)C=1NC2=C3C(C=CC2=CC=1)=NN=C3 Chemical compound N1(CCOCC1)C=1NC2=C3C(C=CC2=CC=1)=NN=C3 CJRBZQVGAHWBFY-UHFFFAOYSA-N 0.000 description 1
- 229910003251 Na K Inorganic materials 0.000 description 1
- QWVWJTRZUIOEEJ-UHFFFAOYSA-N O=C1C2=CNC=3C=C(N4CCNCCC4)C(F)=CC=3C2=NN1C1=CC=CC=C1 Chemical compound O=C1C2=CNC=3C=C(N4CCNCCC4)C(F)=CC=3C2=NN1C1=CC=CC=C1 QWVWJTRZUIOEEJ-UHFFFAOYSA-N 0.000 description 1
- WJVPSUUIKJOGIF-UHFFFAOYSA-N O=C1N(C=2C=CC=CC=2)N=C(C2=C3)C1=CNC2=CC=C3N1CCCCC1 Chemical compound O=C1N(C=2C=CC=CC=2)N=C(C2=C3)C1=CNC2=CC=C3N1CCCCC1 WJVPSUUIKJOGIF-UHFFFAOYSA-N 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 208000000609 Pick Disease of the Brain Diseases 0.000 description 1
- LHNKBXRFNPMIBR-UHFFFAOYSA-N Picrotoxin Natural products CC(C)(O)C1(O)C2OC(=O)C1C3(O)C4OC4C5C(=O)OC2C35C LHNKBXRFNPMIBR-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical class [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 101710137500 T7 RNA polymerase Proteins 0.000 description 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- QOTAEASRCGCJDN-UHFFFAOYSA-N [C].CO Chemical compound [C].CO QOTAEASRCGCJDN-UHFFFAOYSA-N 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 150000008043 acidic salts Chemical class 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 230000008484 agonism 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
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000004450 alkenylene group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229940124277 aminobutyric acid Drugs 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- UKXZWEDNEGGXQX-UHFFFAOYSA-N aniline;piperidine Chemical compound C1CCNCC1.NC1=CC=CC=C1 UKXZWEDNEGGXQX-UHFFFAOYSA-N 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 230000000949 anxiolytic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 150000005840 aryl radicals Chemical class 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 229940125717 barbiturate Drugs 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- 150000001557 benzodiazepines Chemical class 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 239000005388 borosilicate glass Substances 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000002475 cognitive enhancer Substances 0.000 description 1
- 230000036992 cognitive tasks Effects 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000006165 cyclic alkyl group Chemical group 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 150000001934 cyclohexanes Chemical group 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 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
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000000816 effect on animals Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- VTLWFGZACOOWFR-UHFFFAOYSA-N ethyl 4,7-dichloro-6-fluoroquinoline-3-carboxylate Chemical compound C1=C(Cl)C(F)=CC2=C(Cl)C(C(=O)OCC)=CN=C21 VTLWFGZACOOWFR-UHFFFAOYSA-N 0.000 description 1
- NPHOWQSOIPSSGR-UHFFFAOYSA-N ethyl 4-chloro-7-morpholin-4-ylquinoline-3-carboxylate Chemical compound C1=CC2=C(Cl)C(C(=O)OCC)=CN=C2C=C1N1CCOCC1 NPHOWQSOIPSSGR-UHFFFAOYSA-N 0.000 description 1
- ONQDAESGZUODFI-UHFFFAOYSA-N ethyl 6,7,8-trifluoro-4-oxo-1h-quinoline-3-carboxylate Chemical compound FC1=C(F)C=C2C(=O)C(C(=O)OCC)=CNC2=C1F ONQDAESGZUODFI-UHFFFAOYSA-N 0.000 description 1
- 239000000374 eutectic mixture Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000013213 extrapolation Methods 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 230000003325 follicular Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 125000005908 glyceryl ester group Chemical group 0.000 description 1
- 239000001087 glyceryl triacetate Substances 0.000 description 1
- 235000013773 glyceryl triacetate Nutrition 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000011141 high resolution liquid chromatography Methods 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229910000103 lithium hydride Inorganic materials 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
- 238000012423 maintenance Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000005056 memory consolidation Effects 0.000 description 1
- 230000006386 memory function Effects 0.000 description 1
- 206010027175 memory impairment Diseases 0.000 description 1
- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000009149 molecular binding Effects 0.000 description 1
- YFJAIURZMRJPDB-UHFFFAOYSA-N n,n-dimethylpiperidin-4-amine Chemical compound CN(C)C1CCNCC1 YFJAIURZMRJPDB-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
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen(.) Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- OIPZNTLJVJGRCI-UHFFFAOYSA-M octadecanoyloxyaluminum;dihydrate Chemical compound O.O.CCCCCCCCCCCCCCCCCC(=O)O[Al] OIPZNTLJVJGRCI-UHFFFAOYSA-M 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- VJKUPQSHOVKBCO-AHMKVGDJSA-N picrotoxin Chemical compound O=C([C@@]12O[C@@H]1C[C@]1(O)[C@@]32C)O[C@@H]3[C@H]2[C@@H](C(=C)C)[C@@H]1C(=O)O2.O=C([C@@]12O[C@@H]1C[C@]1(O)[C@@]32C)O[C@@H]3[C@H]2[C@@H](C(C)(O)C)[C@@H]1C(=O)O2 VJKUPQSHOVKBCO-AHMKVGDJSA-N 0.000 description 1
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 1
- BRRMEKWBTRNYBF-UHFFFAOYSA-N piperidine;1h-quinolin-2-one Chemical compound C1CCNCC1.C1=CC=CC2=NC(O)=CC=C21 BRRMEKWBTRNYBF-UHFFFAOYSA-N 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000000651 prodrug Chemical class 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- HREHOXSRYOZKNT-UHFFFAOYSA-N quinolin-2-ylmethanol Chemical compound C1=CC=CC2=NC(CO)=CC=C21 HREHOXSRYOZKNT-UHFFFAOYSA-N 0.000 description 1
- PMZDQRJGMBOQBF-UHFFFAOYSA-N quinolin-4-ol Chemical compound C1=CC=C2C(O)=CC=NC2=C1 PMZDQRJGMBOQBF-UHFFFAOYSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000002787 reinforcement Effects 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007892 solid unit dosage form Substances 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000009182 swimming Effects 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000003419 tautomerization reaction Methods 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
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- 229940072040 tricaine Drugs 0.000 description 1
- FQZJYWMRQDKBQN-UHFFFAOYSA-N tricaine methanesulfonate Chemical compound CS([O-])(=O)=O.CCOC(=O)C1=CC=CC([NH3+])=C1 FQZJYWMRQDKBQN-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 229960001475 zolpidem Drugs 0.000 description 1
- ZAFYATHCZYHLPB-UHFFFAOYSA-N zolpidem Chemical compound N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1 ZAFYATHCZYHLPB-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—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
- A61P25/22—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
- A61P25/28—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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Anesthesiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US94300507P | 2007-06-08 | 2007-06-08 | |
| US943005P | 2007-06-08 | ||
| PCT/US2008/066201 WO2008154438A1 (en) | 2007-06-08 | 2008-06-06 | Therapeutic pyrazoloquinoline derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2386168T3 true ES2386168T3 (es) | 2012-08-10 |
Family
ID=40096440
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES08770402T Active ES2386168T3 (es) | 2007-06-08 | 2008-06-06 | Derivados de pirazoloquinolina terapéuticos |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US7872002B2 (enExample) |
| EP (1) | EP2166852B1 (enExample) |
| JP (1) | JP2010529143A (enExample) |
| KR (1) | KR20100039331A (enExample) |
| CN (1) | CN101742908A (enExample) |
| AT (1) | ATE544344T1 (enExample) |
| AU (1) | AU2008261884A1 (enExample) |
| BR (1) | BRPI0812366A2 (enExample) |
| CA (1) | CA2688395A1 (enExample) |
| ES (1) | ES2386168T3 (enExample) |
| IL (1) | IL202270A0 (enExample) |
| MX (1) | MX2009013202A (enExample) |
| WO (1) | WO2008154438A1 (enExample) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2483728T3 (es) * | 2007-06-08 | 2014-08-07 | Dart Neuroscience (Cayman) Ltd | Derivados terapéuticos de pirazolonafatiridina |
| ES2386168T3 (es) * | 2007-06-08 | 2012-08-10 | Helicon Therapeutics, Inc. | Derivados de pirazoloquinolina terapéuticos |
| US7863266B2 (en) * | 2007-06-08 | 2011-01-04 | Helicon Therapeutics, Inc. | Therapeutic pyrazoloquinoline urea derivatives |
| US20150374705A1 (en) | 2012-02-14 | 2015-12-31 | Shanghai Institues for Biological Sciences | Substances for treatment or relief of pain |
| WO2017085053A1 (en) | 2015-11-16 | 2017-05-26 | Fundación Para La Investigación Médica Aplicada | Novel compounds as inhibitors of dna methyltransferases |
| CN105294648B (zh) * | 2015-11-30 | 2017-11-28 | 山东罗欣药业集团股份有限公司 | 一种西他沙星的制备方法 |
| CN116390923B (zh) * | 2020-08-21 | 2025-08-29 | 浙江海正药业股份有限公司 | 杂环类衍生物及其制备方法和用途 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3204126A1 (de) * | 1982-02-06 | 1983-08-11 | Bayer Ag, 5090 Leverkusen | Pyrazoloxazine, -thiazine, -chinoline, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
| US4814450A (en) | 1984-07-09 | 1989-03-21 | Ciba-Geigy Corporation | Certain ring-fused pyrazolo[3,4-d]-pyridin-3-one derivatives |
| JPS61112075A (ja) * | 1984-11-05 | 1986-05-30 | Shionogi & Co Ltd | チエニルピラゾロキノリン誘導体 |
| EP0214092A1 (en) | 1985-08-08 | 1987-03-11 | Ciba-Geigy Ag | Enhanced absorption of psychoactive 2-aryl-pyrazolo quinolines as a solid molecular dispersion in polyvinylpyrrolidone |
| US5334595A (en) * | 1992-10-23 | 1994-08-02 | Sterling Winthrop Inc. | Pyrazoloquinolones as anticancer agents |
| GB9716347D0 (en) * | 1997-08-01 | 1997-10-08 | Merck Sharp & Dohme | Therapeutic compounds |
| TWI271406B (en) | 1999-12-13 | 2007-01-21 | Eisai Co Ltd | Tricyclic condensed heterocyclic compounds, preparation method of the same and pharmaceuticals comprising the same |
| GB0108475D0 (en) * | 2001-04-04 | 2001-05-23 | Merck Sharp & Dohme | New compounds |
| JP3896309B2 (ja) * | 2001-07-09 | 2007-03-22 | ファイザー株式会社 | プロテインキナーゼｃ阻害物質としてのピラゾロキノリノン誘導体 |
| ATE425164T1 (de) | 2002-12-16 | 2009-03-15 | Active Biotech Ab | Tetrazyklische immunmodulierende verbindungen |
| AR045689A1 (es) | 2003-05-29 | 2005-11-09 | Millennium Pharm Inc | Compuestos derivados de 2,5-dihidro-pirazolo[4,3-c]quinolin-4-ona como inhibidores de chk-1 y composiciones farmaceuticas que los contienen |
| US7544697B2 (en) | 2003-10-03 | 2009-06-09 | Coley Pharmaceutical Group, Inc. | Pyrazolopyridines and analogs thereof |
| AU2006287378A1 (en) | 2005-09-07 | 2007-03-15 | Braincells, Inc. | Modulation of neurogenesis by HDac inhibition |
| JP2008047893A (ja) * | 2006-08-11 | 2008-02-28 | Samsung Electronics Co Ltd | 薄膜トランジスタ表示板及びその製造方法 |
| ES2386168T3 (es) * | 2007-06-08 | 2012-08-10 | Helicon Therapeutics, Inc. | Derivados de pirazoloquinolina terapéuticos |
-
2008
- 2008-06-06 ES ES08770402T patent/ES2386168T3/es active Active
- 2008-06-06 KR KR1020107000330A patent/KR20100039331A/ko not_active Withdrawn
- 2008-06-06 CN CN200880024823A patent/CN101742908A/zh active Pending
- 2008-06-06 US US12/135,036 patent/US7872002B2/en not_active Expired - Fee Related
- 2008-06-06 EP EP08770402A patent/EP2166852B1/en not_active Not-in-force
- 2008-06-06 MX MX2009013202A patent/MX2009013202A/es active IP Right Grant
- 2008-06-06 AT AT08770402T patent/ATE544344T1/de active
- 2008-06-06 CA CA002688395A patent/CA2688395A1/en not_active Abandoned
- 2008-06-06 AU AU2008261884A patent/AU2008261884A1/en not_active Abandoned
- 2008-06-06 BR BRPI0812366A patent/BRPI0812366A2/pt not_active IP Right Cessation
- 2008-06-06 WO PCT/US2008/066201 patent/WO2008154438A1/en not_active Ceased
- 2008-06-06 JP JP2010511387A patent/JP2010529143A/ja active Pending
-
2009
- 2009-11-22 IL IL202270A patent/IL202270A0/en unknown
-
2010
- 2010-11-18 US US12/949,655 patent/US8598159B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN101742908A (zh) | 2010-06-16 |
| JP2010529143A (ja) | 2010-08-26 |
| ATE544344T1 (de) | 2012-02-15 |
| AU2008261884A1 (en) | 2008-12-18 |
| EP2166852A1 (en) | 2010-03-31 |
| IL202270A0 (en) | 2010-06-16 |
| BRPI0812366A2 (pt) | 2016-08-02 |
| EP2166852B1 (en) | 2012-02-08 |
| US20110065693A1 (en) | 2011-03-17 |
| HK1142775A1 (en) | 2010-12-17 |
| US8598159B2 (en) | 2013-12-03 |
| US7872002B2 (en) | 2011-01-18 |
| MX2009013202A (es) | 2010-04-09 |
| US20080306049A1 (en) | 2008-12-11 |
| EP2166852A4 (en) | 2010-07-07 |
| WO2008154438A1 (en) | 2008-12-18 |
| CA2688395A1 (en) | 2008-12-18 |
| KR20100039331A (ko) | 2010-04-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2386168T3 (es) | Derivados de pirazoloquinolina terapéuticos | |
| ES2433566T3 (es) | Derivados terapéuticos de pirazoloquinolinurea | |
| ES2483728T3 (es) | Derivados terapéuticos de pirazolonafatiridina | |
| JP2010529145A5 (enExample) | ||
| ES2897050T3 (es) | Derivados de imidazopiridina y el uso de los mismos como medicamento | |
| ES2251316B1 (es) | Inhibidores del receptor sigma. | |
| CN115215883A (zh) | Usp7抑制剂 | |
| HK1142775B (en) | Therapeutic pyrazoloquinoline derivatives | |
| HK1142496B (en) | Therapeutic pyrazoloquinoline urea derivatives | |
| HK1142774B (en) | Therapeutic pyrazolonaphthyridine derivatives | |
| HK1144891A (zh) | 治疗用吡唑并喹啉衍生物 | |
| HK1142776A (en) | Therapeutic pyrazoloquinoline urea derivatives |