JP2010529144A - 治療用ピラゾロキノリン尿素誘導体 - Google Patents
治療用ピラゾロキノリン尿素誘導体 Download PDFInfo
- Publication number
- JP2010529144A JP2010529144A JP2010511389A JP2010511389A JP2010529144A JP 2010529144 A JP2010529144 A JP 2010529144A JP 2010511389 A JP2010511389 A JP 2010511389A JP 2010511389 A JP2010511389 A JP 2010511389A JP 2010529144 A JP2010529144 A JP 2010529144A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- aryl
- compound according
- fluoro
- animal
- 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.)
- Pending
Links
- 230000001225 therapeutic effect Effects 0.000 title description 3
- PBUWKCRTSMWDRY-UHFFFAOYSA-N NC(N)=O.C1=CNC2=C3C=NN=C3C=CC2=C1 Chemical class NC(N)=O.C1=CNC2=C3C=NN=C3C=CC2=C1 PBUWKCRTSMWDRY-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 196
- 238000000034 method Methods 0.000 claims abstract description 118
- 241001465754 Metazoa Species 0.000 claims abstract description 63
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims abstract description 58
- 229960003692 gamma aminobutyric acid Drugs 0.000 claims abstract description 55
- 239000003814 drug Substances 0.000 claims abstract description 19
- 238000004519 manufacturing process Methods 0.000 claims abstract description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 6
- 125000003118 aryl group Chemical group 0.000 claims description 80
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 60
- 125000001153 fluoro group Chemical group F* 0.000 claims description 50
- 150000003839 salts Chemical class 0.000 claims description 50
- 229910052739 hydrogen Inorganic materials 0.000 claims description 46
- 239000001257 hydrogen Substances 0.000 claims description 45
- 125000000217 alkyl group Chemical group 0.000 claims description 41
- -1 Ring Chemical group 0.000 claims description 38
- 125000000623 heterocyclic group Chemical group 0.000 claims description 31
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 26
- 230000015654 memory Effects 0.000 claims description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 22
- 125000001072 heteroaryl group Chemical group 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 21
- 125000005843 halogen group Chemical group 0.000 claims description 20
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 16
- 208000010877 cognitive disease Diseases 0.000 claims description 16
- 229910052760 oxygen Inorganic materials 0.000 claims description 16
- 239000001301 oxygen Substances 0.000 claims description 16
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 13
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 125000004043 oxo group Chemical group O=* 0.000 claims description 9
- 230000003920 cognitive function Effects 0.000 claims description 8
- 208000024827 Alzheimer disease Diseases 0.000 claims description 7
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 7
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 6
- 230000007787 long-term memory Effects 0.000 claims description 6
- 230000006403 short-term memory Effects 0.000 claims description 6
- 125000002757 morpholinyl group Chemical group 0.000 claims description 5
- 230000001105 regulatory effect Effects 0.000 claims description 5
- 208000028698 Cognitive impairment Diseases 0.000 claims description 4
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- 208000020016 psychiatric disease Diseases 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- 201000000980 schizophrenia Diseases 0.000 claims description 4
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 4
- 208000019901 Anxiety disease Diseases 0.000 claims description 3
- 230000004770 neurodegeneration Effects 0.000 claims description 3
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 230000001668 ameliorated effect Effects 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 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 class 0.000 claims 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 2
- 229910003827 NRaRb Inorganic materials 0.000 claims 1
- 229940049706 benzodiazepine Drugs 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
- 230000027455 binding Effects 0.000 abstract description 5
- 208000035475 disorder Diseases 0.000 abstract description 4
- 239000000126 substance Substances 0.000 abstract description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 74
- 230000015572 biosynthetic process Effects 0.000 description 38
- 238000003786 synthesis reaction Methods 0.000 description 37
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- 0 CN=C([C@](C1*)C(*c2ccccc2)=O)c2c(*)c(*)c(*)c(*)c2N1C(N(*)*)=O Chemical compound CN=C([C@](C1*)C(*c2ccccc2)=O)c2c(*)c(*)c(*)c(*)c2N1C(N(*)*)=O 0.000 description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 21
- 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 20
- 239000000243 solution Substances 0.000 description 20
- 238000012549 training Methods 0.000 description 19
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 18
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 18
- 239000002904 solvent Substances 0.000 description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- WHKWMTXTYKVFLK-UHFFFAOYSA-N 1-propan-2-ylpiperazine Chemical compound CC(C)N1CCNCC1 WHKWMTXTYKVFLK-UHFFFAOYSA-N 0.000 description 14
- UZOFELREXGAFOI-UHFFFAOYSA-N 4-methylpiperidine Chemical compound CC1CCNCC1 UZOFELREXGAFOI-UHFFFAOYSA-N 0.000 description 14
- 102000005962 receptors Human genes 0.000 description 14
- 108020003175 receptors Proteins 0.000 description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 210000000287 oocyte Anatomy 0.000 description 11
- 150000003254 radicals Chemical class 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 10
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 10
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 239000002299 complementary DNA Substances 0.000 description 9
- 125000004122 cyclic group Chemical group 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 9
- 229940067157 phenylhydrazine Drugs 0.000 description 9
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 8
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical group CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 8
- 125000005842 heteroatom Chemical group 0.000 description 8
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 210000004556 brain Anatomy 0.000 description 7
- 239000002552 dosage form Substances 0.000 description 7
- 230000014759 maintenance of location Effects 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
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000012320 chlorinating reagent Substances 0.000 description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- YBEOYBKKSWUSBR-UHFFFAOYSA-N ethyl 4-oxo-1h-quinoline-3-carboxylate Chemical compound C1=CC=C2C(=O)C(C(=O)OCC)=CNC2=C1 YBEOYBKKSWUSBR-UHFFFAOYSA-N 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 5
- 231100000252 nontoxic Toxicity 0.000 description 5
- 230000003000 nontoxic effect Effects 0.000 description 5
- 239000013612 plasmid Substances 0.000 description 5
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 5
- DNTFNRUPWKYWSS-UHFFFAOYSA-N 5-(2,6-dimethylmorpholine-4-carbonyl)-2-phenylpyrazolo[4,3-c]quinolin-3-one Chemical compound C1C(C)OC(C)CN1C(=O)N(C=C1C2=O)C3=CC=CC=C3C1=NN2C1=CC=CC=C1 DNTFNRUPWKYWSS-UHFFFAOYSA-N 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 4
- 241000283984 Rodentia Species 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000000556 agonist Substances 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 125000002950 monocyclic group Chemical group 0.000 description 4
- KPADFPAILITQBG-UHFFFAOYSA-N non-4-ene Chemical compound CCCCC=CCCC KPADFPAILITQBG-UHFFFAOYSA-N 0.000 description 4
- 150000007530 organic bases Chemical class 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 229910052717 sulfur Inorganic materials 0.000 description 4
- 239000011593 sulfur Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- FXHRAKUEZPSMLJ-UHFFFAOYSA-N 1-methyl-1,4-diazepane Chemical compound CN1CCCNCC1 FXHRAKUEZPSMLJ-UHFFFAOYSA-N 0.000 description 3
- VNHGABOGOPLOEP-UHFFFAOYSA-N 2-phenyl-5-(4-propan-2-ylpiperazine-1-carbonyl)pyrazolo[4,3-c]quinolin-3-one Chemical compound C1CN(C(C)C)CCN1C(=O)N(C=C1C2=O)C3=CC=CC=C3C1=NN2C1=CC=CC=C1 VNHGABOGOPLOEP-UHFFFAOYSA-N 0.000 description 3
- IFUKGDCNRBNQQV-UHFFFAOYSA-N 4-methyl-5-(4-methylpiperazine-1-carbonyl)-2-phenylpyrazolo[4,3-c]quinolin-3-one Chemical compound C1CN(C)CCN1C(=O)N(C(C)=C1C2=O)C3=CC=CC=C3C1=NN2C1=CC=CC=C1 IFUKGDCNRBNQQV-UHFFFAOYSA-N 0.000 description 3
- VGJNWUIIFHHBCL-UHFFFAOYSA-N 7,8-difluoro-4-methyl-5-(4-methylpiperazine-1-carbonyl)-2-phenylpyrazolo[4,3-c]quinolin-3-one Chemical compound C1CN(C)CCN1C(=O)N(C(C)=C1C2=O)C3=CC(F)=C(F)C=C3C1=NN2C1=CC=CC=C1 VGJNWUIIFHHBCL-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 206010012218 Delirium Diseases 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 125000003342 alkenyl group Chemical group 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000004202 carbamide Substances 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- LTMHNWPUDSTBKD-UHFFFAOYSA-N diethyl 2-(ethoxymethylidene)propanedioate Chemical compound CCOC=C(C(=O)OCC)C(=O)OCC LTMHNWPUDSTBKD-UHFFFAOYSA-N 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- IXMRUGGFGJIANG-UHFFFAOYSA-N ethyl 4-chloro-7-methoxyquinoline-3-carboxylate Chemical compound C1=C(OC)C=CC2=C(Cl)C(C(=O)OCC)=CN=C21 IXMRUGGFGJIANG-UHFFFAOYSA-N 0.000 description 3
- DWXQUAHMZWZXHP-UHFFFAOYSA-N ethyl 4-chloroquinoline-3-carboxylate Chemical compound C1=CC=CC2=C(Cl)C(C(=O)OCC)=CN=C21 DWXQUAHMZWZXHP-UHFFFAOYSA-N 0.000 description 3
- GWLDDWJZROMBRD-UHFFFAOYSA-N ethyl 7-methoxy-4-oxo-1h-quinoline-3-carboxylate Chemical compound COC1=CC=C2C(=O)C(C(=O)OCC)=CNC2=C1 GWLDDWJZROMBRD-UHFFFAOYSA-N 0.000 description 3
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 208000027061 mild cognitive impairment Diseases 0.000 description 3
- 229940078552 o-xylene Drugs 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 230000010412 perfusion Effects 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 230000003936 working memory Effects 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- 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 2
- QLEIDMAURCRVCX-UHFFFAOYSA-N 1-propylpiperazine Chemical compound CCCN1CCNCC1 QLEIDMAURCRVCX-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- IFNWESYYDINUHV-UHFFFAOYSA-N 2,6-dimethylpiperazine Chemical compound CC1CNCC(C)N1 IFNWESYYDINUHV-UHFFFAOYSA-N 0.000 description 2
- GXPLMHQNHHSWIX-UHFFFAOYSA-N 2-(2-fluorophenyl)-5-(4-methylpiperazine-1-carbonyl)pyrazolo[4,3-c]quinolin-3-one Chemical compound C1CN(C)CCN1C(=O)N(C=C1C2=O)C3=CC=CC=C3C1=NN2C1=CC=CC=C1F GXPLMHQNHHSWIX-UHFFFAOYSA-N 0.000 description 2
- FQVROEZGDGKGCO-UHFFFAOYSA-N 2-(2-fluorophenyl)-5-(4-propan-2-ylpiperazine-1-carbonyl)pyrazolo[4,3-c]quinolin-3-one Chemical compound C1CN(C(C)C)CCN1C(=O)N(C=C1C2=O)C3=CC=CC=C3C1=NN2C1=CC=CC=C1F FQVROEZGDGKGCO-UHFFFAOYSA-N 0.000 description 2
- GXSKUVANTJCWPA-UHFFFAOYSA-N 2-(4-chlorophenyl)-8-fluoro-5-(4-propan-2-ylpiperazine-1-carbonyl)pyrazolo[4,3-c]quinolin-3-one Chemical compound C1CN(C(C)C)CCN1C(=O)N(C=C1C2=O)C3=CC=C(F)C=C3C1=NN2C1=CC=C(Cl)C=C1 GXSKUVANTJCWPA-UHFFFAOYSA-N 0.000 description 2
- FTHGIXILGYJOBQ-UHFFFAOYSA-N 2-(4-methoxyphenyl)-1h-pyrazolo[4,3-c]quinolin-3-one Chemical compound C1=CC(OC)=CC=C1N1C(=O)C(C=NC=2C3=CC=CC=2)=C3N1 FTHGIXILGYJOBQ-UHFFFAOYSA-N 0.000 description 2
- PPBSILMSQCCGOB-UHFFFAOYSA-N 2-(4-methoxyphenyl)-5-(4-methylpiperazine-1-carbonyl)pyrazolo[4,3-c]quinolin-3-one Chemical compound C1=CC(OC)=CC=C1N(N=C1C2=CC=CC=C22)C(=O)C1=CN2C(=O)N1CCN(C)CC1 PPBSILMSQCCGOB-UHFFFAOYSA-N 0.000 description 2
- HWHUVRBCNRULEI-UHFFFAOYSA-N 2-(4-methoxyphenyl)-5-(4-propan-2-ylpiperazine-1-carbonyl)pyrazolo[4,3-c]quinolin-3-one Chemical compound C1=CC(OC)=CC=C1N(N=C1C2=CC=CC=C22)C(=O)C1=CN2C(=O)N1CCN(C(C)C)CC1 HWHUVRBCNRULEI-UHFFFAOYSA-N 0.000 description 2
- DDEAEWMDOSXKBX-UHFFFAOYSA-N 2-(chloromethyl)quinoline Chemical compound C1=CC=CC2=NC(CCl)=CC=C21 DDEAEWMDOSXKBX-UHFFFAOYSA-N 0.000 description 2
- OFUFXTHGZWIDDB-UHFFFAOYSA-N 2-chloroquinoline Chemical class C1=CC=CC2=NC(Cl)=CC=C21 OFUFXTHGZWIDDB-UHFFFAOYSA-N 0.000 description 2
- CFTOXVOLWKANEK-UHFFFAOYSA-N 2-phenyl-5-(4-phenylpiperazine-1-carbonyl)pyrazolo[4,3-c]quinolin-3-one Chemical compound C1=C(C(N(C=2C=CC=CC=2)N=2)=O)C=2C2=CC=CC=C2N1C(=O)N(CC1)CCN1C1=CC=CC=C1 CFTOXVOLWKANEK-UHFFFAOYSA-N 0.000 description 2
- HMPPSULFLKVHIP-UHFFFAOYSA-N 2-phenyl-5-(4-propan-2-ylpiperazine-1-carbonyl)-8-(trifluoromethyl)pyrazolo[4,3-c]quinolin-3-one Chemical compound C1CN(C(C)C)CCN1C(=O)N(C=C1C2=O)C3=CC=C(C(F)(F)F)C=C3C1=NN2C1=CC=CC=C1 HMPPSULFLKVHIP-UHFFFAOYSA-N 0.000 description 2
- VZVUSBZZAMHUOW-UHFFFAOYSA-N 2-phenyl-5-(4-propylpiperazine-1-carbonyl)pyrazolo[4,3-c]quinolin-3-one Chemical compound C1CN(CCC)CCN1C(=O)N(C=C1C2=O)C3=CC=CC=C3C1=NN2C1=CC=CC=C1 VZVUSBZZAMHUOW-UHFFFAOYSA-N 0.000 description 2
- MNTQCSSJDKTDCL-UHFFFAOYSA-N 2-phenyl-5-(piperidine-1-carbonyl)pyrazolo[4,3-c]quinolin-3-one Chemical compound C1=C(C(N(C=2C=CC=CC=2)N=2)=O)C=2C2=CC=CC=C2N1C(=O)N1CCCCC1 MNTQCSSJDKTDCL-UHFFFAOYSA-N 0.000 description 2
- WKVRMXTWADZROP-UHFFFAOYSA-N 4-methyl-2-phenyl-5-(4-propan-2-ylpiperazine-1-carbonyl)pyrazolo[4,3-c]quinolin-3-one Chemical compound C1CN(C(C)C)CCN1C(=O)N(C(C)=C1C2=O)C3=CC=CC=C3C1=NN2C1=CC=CC=C1 WKVRMXTWADZROP-UHFFFAOYSA-N 0.000 description 2
- GEKOQAKGWNFMEB-UHFFFAOYSA-N 5-(2-methylpyrrolidine-1-carbonyl)-2-phenylpyrazolo[4,3-c]quinolin-3-one Chemical compound CC1CCCN1C(=O)N(C=C1C2=O)C3=CC=CC=C3C1=NN2C1=CC=CC=C1 GEKOQAKGWNFMEB-UHFFFAOYSA-N 0.000 description 2
- UNWWLAFIYSUDTG-UHFFFAOYSA-N 5-(3,5-dimethylpiperazine-1-carbonyl)-2-phenylpyrazolo[4,3-c]quinolin-3-one Chemical compound C1C(C)NC(C)CN1C(=O)N(C=C1C2=O)C3=CC=CC=C3C1=NN2C1=CC=CC=C1 UNWWLAFIYSUDTG-UHFFFAOYSA-N 0.000 description 2
- QXSXIYSQIKYLQK-UHFFFAOYSA-N 5-(4-fluoropiperidine-1-carbonyl)-8-methyl-2-phenylpyrazolo[4,3-c]quinolin-3-one Chemical compound C12=CC(C)=CC=C2N(C(=O)N2CCC(F)CC2)C=C(C2=O)C1=NN2C1=CC=CC=C1 QXSXIYSQIKYLQK-UHFFFAOYSA-N 0.000 description 2
- XLAHEOVKHSSCAX-UHFFFAOYSA-N 5-(4-hydroxypiperidine-1-carbonyl)-2-phenylpyrazolo[4,3-c]quinolin-3-one Chemical compound C1CC(O)CCN1C(=O)N(C=C1C2=O)C3=CC=CC=C3C1=NN2C1=CC=CC=C1 XLAHEOVKHSSCAX-UHFFFAOYSA-N 0.000 description 2
- TWTGZAZIAVATGW-UHFFFAOYSA-N 5-(4-hydroxypiperidine-1-carbonyl)-8-methyl-2-phenylpyrazolo[4,3-c]quinolin-3-one Chemical compound C12=CC(C)=CC=C2N(C(=O)N2CCC(O)CC2)C=C(C2=O)C1=NN2C1=CC=CC=C1 TWTGZAZIAVATGW-UHFFFAOYSA-N 0.000 description 2
- YDDCVNQYUBLUJT-UHFFFAOYSA-N 5-(4-methylpiperazine-1-carbonyl)-2-phenyl-8-(trifluoromethyl)pyrazolo[4,3-c]quinolin-3-one Chemical compound C1CN(C)CCN1C(=O)N(C=C1C2=O)C3=CC=C(C(F)(F)F)C=C3C1=NN2C1=CC=CC=C1 YDDCVNQYUBLUJT-UHFFFAOYSA-N 0.000 description 2
- DQVQVLDJWDPLCH-UHFFFAOYSA-N 5-(4-methylpiperazine-1-carbonyl)-2-phenylpyrazolo[4,3-c]quinolin-3-one Chemical compound C1CN(C)CCN1C(=O)N(C=C1C2=O)C3=CC=CC=C3C1=NN2C1=CC=CC=C1 DQVQVLDJWDPLCH-UHFFFAOYSA-N 0.000 description 2
- SKBFTMUJXQJVFI-UHFFFAOYSA-N 5-(4-methylpiperidine-1-carbonyl)-2-phenylpyrazolo[4,3-c]quinolin-3-one Chemical compound C1CC(C)CCN1C(=O)N(C=C1C2=O)C3=CC=CC=C3C1=NN2C1=CC=CC=C1 SKBFTMUJXQJVFI-UHFFFAOYSA-N 0.000 description 2
- MYIQDYBBLAHQHP-UHFFFAOYSA-N 5-(morpholine-4-carbonyl)-2-phenylpyrazolo[4,3-c]quinolin-3-one Chemical compound C1=C(C(N(C=2C=CC=CC=2)N=2)=O)C=2C2=CC=CC=C2N1C(=O)N1CCOCC1 MYIQDYBBLAHQHP-UHFFFAOYSA-N 0.000 description 2
- JMOACJNFIHMLSX-UHFFFAOYSA-N 5-[4-(2-methoxyethyl)piperazine-1-carbonyl]-2-phenylpyrazolo[4,3-c]quinolin-3-one Chemical compound C1CN(CCOC)CCN1C(=O)N(C=C1C2=O)C3=CC=CC=C3C1=NN2C1=CC=CC=C1 JMOACJNFIHMLSX-UHFFFAOYSA-N 0.000 description 2
- XICVMLIIZYCRBC-UHFFFAOYSA-N 7,8-difluoro-2-phenyl-5-(4-propan-2-ylpiperazine-1-carbonyl)pyrazolo[4,3-c]quinolin-3-one Chemical compound C1CN(C(C)C)CCN1C(=O)N(C=C1C2=O)C3=CC(F)=C(F)C=C3C1=NN2C1=CC=CC=C1 XICVMLIIZYCRBC-UHFFFAOYSA-N 0.000 description 2
- ULCXEFRRVHAYNK-UHFFFAOYSA-N 7,8-difluoro-4-methyl-2-phenyl-5-(4-propan-2-ylpiperazine-1-carbonyl)pyrazolo[4,3-c]quinolin-3-one Chemical compound C1CN(C(C)C)CCN1C(=O)N(C(C)=C1C2=O)C3=CC(F)=C(F)C=C3C1=NN2C1=CC=CC=C1 ULCXEFRRVHAYNK-UHFFFAOYSA-N 0.000 description 2
- PAGXMSKWBXVYRT-UHFFFAOYSA-N 7,8-difluoro-5-(4-hydroxypiperidine-1-carbonyl)-2-phenylpyrazolo[4,3-c]quinolin-3-one Chemical compound C1CC(O)CCN1C(=O)N(C=C1C2=O)C3=CC(F)=C(F)C=C3C1=NN2C1=CC=CC=C1 PAGXMSKWBXVYRT-UHFFFAOYSA-N 0.000 description 2
- KONNSSVZGVNLGS-UHFFFAOYSA-N 7,8-difluoro-5-(4-methyl-1,4-diazepane-1-carbonyl)-2-phenylpyrazolo[4,3-c]quinolin-3-one Chemical compound C1CN(C)CCCN1C(=O)N(C=C1C2=O)C3=CC(F)=C(F)C=C3C1=NN2C1=CC=CC=C1 KONNSSVZGVNLGS-UHFFFAOYSA-N 0.000 description 2
- JSTHTKKEEXLGLC-UHFFFAOYSA-N 7,8-difluoro-5-(4-methylpiperazine-1-carbonyl)-2-phenylpyrazolo[4,3-c]quinolin-3-one Chemical compound C1CN(C)CCN1C(=O)N(C=C1C2=O)C3=CC(F)=C(F)C=C3C1=NN2C1=CC=CC=C1 JSTHTKKEEXLGLC-UHFFFAOYSA-N 0.000 description 2
- IZZWJQYWBPSBTB-UHFFFAOYSA-N 7-methoxy-2-phenyl-5-(4-propan-2-ylpiperazine-1-carbonyl)pyrazolo[4,3-c]quinolin-3-one Chemical compound O=C1C2=CN(C(=O)N3CCN(CC3)C(C)C)C3=CC(OC)=CC=C3C2=NN1C1=CC=CC=C1 IZZWJQYWBPSBTB-UHFFFAOYSA-N 0.000 description 2
- 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 2
- AYBQKAMPGOMIFT-UHFFFAOYSA-N 8-fluoro-2-(4-methoxyphenyl)-5-(4-propan-2-ylpiperazine-1-carbonyl)pyrazolo[4,3-c]quinolin-3-one Chemical compound C1=CC(OC)=CC=C1N(N=C1C2=CC(F)=CC=C22)C(=O)C1=CN2C(=O)N1CCN(C(C)C)CC1 AYBQKAMPGOMIFT-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
- IVWUQVIFGUSXTQ-UHFFFAOYSA-N 8-fluoro-2-phenyl-5-(4-phenylpiperazine-1-carbonyl)pyrazolo[4,3-c]quinolin-3-one Chemical compound C12=CC(F)=CC=C2N(C(=O)N2CCN(CC2)C=2C=CC=CC=2)C=C(C2=O)C1=NN2C1=CC=CC=C1 IVWUQVIFGUSXTQ-UHFFFAOYSA-N 0.000 description 2
- IMXLPTQKZYUYKJ-UHFFFAOYSA-N 8-fluoro-2-phenyl-5-(4-propan-2-ylpiperazine-1-carbonyl)pyrazolo[4,3-c]quinolin-3-one Chemical compound C1CN(C(C)C)CCN1C(=O)N(C=C1C2=O)C3=CC=C(F)C=C3C1=NN2C1=CC=CC=C1 IMXLPTQKZYUYKJ-UHFFFAOYSA-N 0.000 description 2
- XUMPMYPGKLTKLI-UHFFFAOYSA-N 8-fluoro-5-(4-methylpiperazine-1-carbonyl)-2-phenylpyrazolo[4,3-c]quinolin-3-one Chemical compound C1CN(C)CCN1C(=O)N(C=C1C2=O)C3=CC=C(F)C=C3C1=NN2C1=CC=CC=C1 XUMPMYPGKLTKLI-UHFFFAOYSA-N 0.000 description 2
- DPZCZIBCCFZMCI-UHFFFAOYSA-N 8-fluoro-7-methyl-5-(4-methylpiperazine-1-carbonyl)-2-phenylpyrazolo[4,3-c]quinolin-3-one Chemical compound C1CN(C)CCN1C(=O)N(C=C1C2=O)C3=CC(C)=C(F)C=C3C1=NN2C1=CC=CC=C1 DPZCZIBCCFZMCI-UHFFFAOYSA-N 0.000 description 2
- VYLRWCGZMBVWLO-UHFFFAOYSA-N 8-methoxy-2-phenyl-1h-pyrazolo[4,3-c]quinolin-3-one Chemical compound C12=CC(OC)=CC=C2N=CC(C2=O)=C1NN2C1=CC=CC=C1 VYLRWCGZMBVWLO-UHFFFAOYSA-N 0.000 description 2
- QYESYGUELIAGKK-UHFFFAOYSA-N 8-methoxy-2-phenyl-5-(4-propan-2-ylpiperazine-1-carbonyl)pyrazolo[4,3-c]quinolin-3-one Chemical compound C12=CC(OC)=CC=C2N(C(=O)N2CCN(CC2)C(C)C)C=C(C2=O)C1=NN2C1=CC=CC=C1 QYESYGUELIAGKK-UHFFFAOYSA-N 0.000 description 2
- QPVPWQAYVUZOGI-UHFFFAOYSA-N 8-methoxy-5-(4-methylpiperazine-1-carbonyl)-2-phenylpyrazolo[4,3-c]quinolin-3-one Chemical compound C12=CC(OC)=CC=C2N(C(=O)N2CCN(C)CC2)C=C(C2=O)C1=NN2C1=CC=CC=C1 QPVPWQAYVUZOGI-UHFFFAOYSA-N 0.000 description 2
- HSAXCHHARCKWQB-UHFFFAOYSA-N 8-methyl-2-phenyl-1h-pyrazolo[4,3-c]quinolin-3-one Chemical compound C12=CC(C)=CC=C2N=CC(C2=O)=C1NN2C1=CC=CC=C1 HSAXCHHARCKWQB-UHFFFAOYSA-N 0.000 description 2
- HOKAPDSIYCPTJZ-UHFFFAOYSA-N 8-methyl-2-phenyl-5-(4-propan-2-ylpiperazine-1-carbonyl)pyrazolo[4,3-c]quinolin-3-one Chemical compound C1CN(C(C)C)CCN1C(=O)N(C=C1C2=O)C3=CC=C(C)C=C3C1=NN2C1=CC=CC=C1 HOKAPDSIYCPTJZ-UHFFFAOYSA-N 0.000 description 2
- PJGXOGHKFFKLJQ-UHFFFAOYSA-N 8-methyl-5-(4-methylpiperazine-1-carbonyl)-2-phenylpyrazolo[4,3-c]quinolin-3-one Chemical compound C1CN(C)CCN1C(=O)N(C=C1C2=O)C3=CC=C(C)C=C3C1=NN2C1=CC=CC=C1 PJGXOGHKFFKLJQ-UHFFFAOYSA-N 0.000 description 2
- STUYKRAELFWFJA-UHFFFAOYSA-N 8-morpholin-4-yl-2-phenyl-5-(4-propan-2-ylpiperazine-1-carbonyl)pyrazolo[4,3-c]quinolin-3-one Chemical compound C1CN(C(C)C)CCN1C(=O)N(C=C1C2=O)C3=CC=C(N4CCOCC4)C=C3C1=NN2C1=CC=CC=C1 STUYKRAELFWFJA-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-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
- XDPVXFCCMDEGJX-UHFFFAOYSA-N C12=CC(C(F)(F)F)=CC=C2NC=C(C2=O)C1=NN2C1=CC=CC=C1 Chemical compound C12=CC(C(F)(F)F)=CC=C2NC=C(C2=O)C1=NN2C1=CC=CC=C1 XDPVXFCCMDEGJX-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
- 241000282693 Cercopithecidae Species 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 2
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 2
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 2
- 206010012289 Dementia Diseases 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 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 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- VMXBYHPSWYSVBE-UHFFFAOYSA-N FC1=CC=CC=C1N1C(=O)C2=CNC3=CC=CC=C3C2=N1 Chemical compound FC1=CC=CC=C1N1C(=O)C2=CNC3=CC=CC=C3C2=N1 VMXBYHPSWYSVBE-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
- 208000023105 Huntington disease Diseases 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 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 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- 229920005372 Plexiglas® Polymers 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 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
- 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
- 150000001336 alkenes Chemical class 0.000 description 2
- 150000001345 alkine derivatives Chemical class 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 230000000949 anxiolytic effect Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 230000003542 behavioural effect Effects 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 125000002619 bicyclic group 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
- 239000012267 brine Substances 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000007958 cherry flavor Substances 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
- 230000001149 cognitive effect Effects 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 239000012043 crude product 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
- 230000003828 downregulation Effects 0.000 description 2
- NQGTXOOKGUUMFE-UHFFFAOYSA-N ethyl 4-chloro-6,7-difluoroquinoline-3-carboxylate Chemical compound C1=C(F)C(F)=CC2=C(Cl)C(C(=O)OCC)=CN=C21 NQGTXOOKGUUMFE-UHFFFAOYSA-N 0.000 description 2
- NYDXGDQZPDDDMR-UHFFFAOYSA-N ethyl 4-chloro-6-(trifluoromethyl)quinoline-3-carboxylate Chemical compound C1=CC(C(F)(F)F)=CC2=C(Cl)C(C(=O)OCC)=CN=C21 NYDXGDQZPDDDMR-UHFFFAOYSA-N 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
- QURGQUFEJWWDRF-UHFFFAOYSA-N ethyl 4-chloro-6-methoxyquinoline-3-carboxylate Chemical compound C1=CC(OC)=CC2=C(Cl)C(C(=O)OCC)=CN=C21 QURGQUFEJWWDRF-UHFFFAOYSA-N 0.000 description 2
- GSIDXMVQPNWNIR-UHFFFAOYSA-N ethyl 4-chloro-6-methylquinoline-3-carboxylate Chemical compound C1=CC(C)=CC2=C(Cl)C(C(=O)OCC)=CN=C21 GSIDXMVQPNWNIR-UHFFFAOYSA-N 0.000 description 2
- SPGPSFWOMJQSDF-UHFFFAOYSA-N ethyl 4-oxo-6-(trifluoromethyl)-1h-quinoline-3-carboxylate Chemical compound C1=C(C(F)(F)F)C=C2C(=O)C(C(=O)OCC)=CNC2=C1 SPGPSFWOMJQSDF-UHFFFAOYSA-N 0.000 description 2
- PVQWGRDZOWBHIC-UHFFFAOYSA-N ethyl 6,7-difluoro-4-oxo-1h-quinoline-3-carboxylate Chemical compound FC1=C(F)C=C2C(=O)C(C(=O)OCC)=CNC2=C1 PVQWGRDZOWBHIC-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
- VNGGYIBIGOOVNP-UHFFFAOYSA-N ethyl 6-methoxy-4-oxo-1h-quinoline-3-carboxylate Chemical compound C1=C(OC)C=C2C(=O)C(C(=O)OCC)=CNC2=C1 VNGGYIBIGOOVNP-UHFFFAOYSA-N 0.000 description 2
- WRHXUGRUTJJRQQ-UHFFFAOYSA-N ethyl 6-methyl-4-oxo-1h-quinoline-3-carboxylate Chemical compound C1=C(C)C=C2C(=O)C(C(=O)OCC)=CNC2=C1 WRHXUGRUTJJRQQ-UHFFFAOYSA-N 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 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
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 210000001320 hippocampus Anatomy 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- VYFOAVADNIHPTR-UHFFFAOYSA-N isatoic anhydride Chemical compound NC1=CC=CC=C1CO VYFOAVADNIHPTR-UHFFFAOYSA-N 0.000 description 2
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- NAFAUTLZTTYDHC-UHFFFAOYSA-N n,n-dimethyl-3-oxo-2-phenylpyrazolo[4,3-c]quinoline-5-carboxamide Chemical compound C12=CC=CC=C2N(C(=O)N(C)C)C=C(C2=O)C1=NN2C1=CC=CC=C1 NAFAUTLZTTYDHC-UHFFFAOYSA-N 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- LKPFBGKZCCBZDK-UHFFFAOYSA-N n-hydroxypiperidine Chemical compound ON1CCCCC1 LKPFBGKZCCBZDK-UHFFFAOYSA-N 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- RZXMPPFPUUCRFN-UHFFFAOYSA-N p-toluidine Chemical compound CC1=CC=C(N)C=C1 RZXMPPFPUUCRFN-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 229960003742 phenol Drugs 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- JOVOSQBPPZZESK-UHFFFAOYSA-N phenylhydrazine hydrochloride Chemical compound Cl.NNC1=CC=CC=C1 JOVOSQBPPZZESK-UHFFFAOYSA-N 0.000 description 2
- 229940038531 phenylhydrazine hydrochloride Drugs 0.000 description 2
- YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical compound C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000004926 polymethyl methacrylate Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- JEXVQSWXXUJEMA-UHFFFAOYSA-N pyrazol-3-one Chemical compound O=C1C=CN=N1 JEXVQSWXXUJEMA-UHFFFAOYSA-N 0.000 description 2
- PMZDQRJGMBOQBF-UHFFFAOYSA-N quinolin-4-ol Chemical compound C1=CC=C2C(O)=CC=NC2=C1 PMZDQRJGMBOQBF-UHFFFAOYSA-N 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
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 229960005322 streptomycin Drugs 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
- 238000010189 synthetic method Methods 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 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
- 239000008096 xylene Substances 0.000 description 2
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
- VFZYLSYYMHFPSY-UHFFFAOYSA-N (2-fluoroanilino)azanium;chloride Chemical compound Cl.NNC1=CC=CC=C1F VFZYLSYYMHFPSY-UHFFFAOYSA-N 0.000 description 1
- FQHCPFMTXFJZJS-UHFFFAOYSA-N (4-methoxyphenyl)hydrazine;hydrochloride Chemical compound Cl.COC1=CC=C(NN)C=C1 FQHCPFMTXFJZJS-UHFFFAOYSA-N 0.000 description 1
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical group NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 description 1
- 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 1
- BMEMBBFDTYHTLH-UHFFFAOYSA-N 1-(2-methoxyethyl)piperazine Chemical compound COCCN1CCNCC1 BMEMBBFDTYHTLH-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
- KDKGWGUUUVROTO-UHFFFAOYSA-N 1-hydroxypiperazine Chemical compound ON1CCNCC1 KDKGWGUUUVROTO-UHFFFAOYSA-N 0.000 description 1
- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 1
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 1
- ZWAQJGHGPPDZSF-UHFFFAOYSA-N 1-prop-2-enylpiperazine Chemical compound C=CCN1CCNCC1 ZWAQJGHGPPDZSF-UHFFFAOYSA-N 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- HNVIQLPOGUDBSU-UHFFFAOYSA-N 2,6-dimethylmorpholine Chemical compound CC1CNCC(C)O1 HNVIQLPOGUDBSU-UHFFFAOYSA-N 0.000 description 1
- NNWUEBIEOFQMSS-UHFFFAOYSA-N 2-Methylpiperidine Chemical compound CC1CCCCN1 NNWUEBIEOFQMSS-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
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
- 125000006020 2-methyl-1-propenyl group Chemical group 0.000 description 1
- RGHPCLZJAFCTIK-UHFFFAOYSA-N 2-methylpyrrolidine Chemical compound CC1CCCN1 RGHPCLZJAFCTIK-UHFFFAOYSA-N 0.000 description 1
- KPGXRSRHYNQIFN-UHFFFAOYSA-N 2-oxoglutaric acid Chemical compound OC(=O)CCC(=O)C(O)=O KPGXRSRHYNQIFN-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
- AXNUZKSSQHTNPZ-UHFFFAOYSA-N 3,4-difluoroaniline Chemical compound NC1=CC=C(F)C(F)=C1 AXNUZKSSQHTNPZ-UHFFFAOYSA-N 0.000 description 1
- ZPGQYQKSLRERDO-UHFFFAOYSA-N 4-(2-methoxyethyl)piperidine Chemical compound COCCC1CCNCC1 ZPGQYQKSLRERDO-UHFFFAOYSA-N 0.000 description 1
- KNDOFJFSHZCKGT-UHFFFAOYSA-N 4-chloroquinoline Chemical compound C1=CC=C2C(Cl)=CC=NC2=C1 KNDOFJFSHZCKGT-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
- QBLLOOKBLTTXHB-UHFFFAOYSA-N 4-fluoropiperidine Chemical compound FC1CCNCC1 QBLLOOKBLTTXHB-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
- ODGIMMLDVSWADK-UHFFFAOYSA-N 4-trifluoromethylaniline Chemical compound NC1=CC=C(C(F)(F)F)C=C1 ODGIMMLDVSWADK-UHFFFAOYSA-N 0.000 description 1
- XMNIOWFLDGXFJS-UHFFFAOYSA-N 6,7-difluoro-1h-quinolin-4-one Chemical compound N1C=CC(=O)C2=C1C=C(F)C(F)=C2 XMNIOWFLDGXFJS-UHFFFAOYSA-N 0.000 description 1
- PIBZIRVQGWORLZ-UHFFFAOYSA-N 7,8-difluoro-2-(4-methoxyphenyl)-5-(4-propan-2-ylpiperazine-1-carbonyl)pyrazolo[4,3-c]quinolin-3-one Chemical compound C1=CC(OC)=CC=C1N(N=C1C2=CC(F)=C(F)C=C22)C(=O)C1=CN2C(=O)N1CCN(C(C)C)CC1 PIBZIRVQGWORLZ-UHFFFAOYSA-N 0.000 description 1
- DNMAALRERITBOO-UHFFFAOYSA-N 7,8-difluoro-5-(4-hydroxypiperidine-1-carbonyl)-2-thiophen-3-ylpyrazolo[4,3-c]quinolin-3-one Chemical compound C1CC(O)CCN1C(=O)N(C=C1C2=O)C3=CC(F)=C(F)C=C3C1=NN2C1=CSC=C1 DNMAALRERITBOO-UHFFFAOYSA-N 0.000 description 1
- UNHRMVNQIJNPPA-UHFFFAOYSA-N 7,8-difluoro-5-(4-methylpiperazine-1-carbonyl)-2-thiophen-3-ylpyrazolo[4,3-c]quinolin-3-one Chemical compound C1CN(C)CCN1C(=O)N(C=C1C2=O)C3=CC(F)=C(F)C=C3C1=NN2C1=CSC=C1 UNHRMVNQIJNPPA-UHFFFAOYSA-N 0.000 description 1
- BUZQHJPWISMWBE-UHFFFAOYSA-N 7-methoxy-2-phenyl-1h-pyrazolo[4,3-c]quinolin-3-one Chemical compound O=C1C=2C=NC3=CC(OC)=CC=C3C=2NN1C1=CC=CC=C1 BUZQHJPWISMWBE-UHFFFAOYSA-N 0.000 description 1
- BVRJQNDBRFHSIM-UHFFFAOYSA-N 8-methyl-5-(4-methyl-1,4-diazepane-1-carbonyl)-2-phenylpyrazolo[4,3-c]quinolin-3-one Chemical compound C1CN(C)CCCN1C(=O)N(C=C1C2=O)C3=CC=C(C)C=C3C1=NN2C1=CC=CC=C1 BVRJQNDBRFHSIM-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 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
- 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
- 241000167854 Bourreria succulenta Species 0.000 description 1
- ICTJCUJLROZKEU-UHFFFAOYSA-N C12=CC(F)=CC=C2NC=C(C2=O)C1=NN2C1=CC=C(Cl)C=C1 Chemical compound C12=CC(F)=CC=C2NC=C(C2=O)C1=NN2C1=CC=C(Cl)C=C1 ICTJCUJLROZKEU-UHFFFAOYSA-N 0.000 description 1
- XRFSCKQYANJBDL-UHFFFAOYSA-N C1=2C=C(F)C(C)=CC=2NC=C(C2=O)C1=NN2C1=CC=CC=C1 Chemical compound C1=2C=C(F)C(C)=CC=2NC=C(C2=O)C1=NN2C1=CC=CC=C1 XRFSCKQYANJBDL-UHFFFAOYSA-N 0.000 description 1
- 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 1
- UUZJRPPVAFLLQT-UHFFFAOYSA-N C1=CC(OC)=CC=C1N1C(=O)C2=CNC3=CC(F)=C(F)C=C3C2=N1 Chemical compound C1=CC(OC)=CC=C1N1C(=O)C2=CNC3=CC(F)=C(F)C=C3C2=N1 UUZJRPPVAFLLQT-UHFFFAOYSA-N 0.000 description 1
- 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 1
- UXYHZIYEDDINQH-UHFFFAOYSA-N C1=CNC2=C3C=NN=C3C=CC2=C1 Chemical compound C1=CNC2=C3C=NN=C3C=CC2=C1 UXYHZIYEDDINQH-UHFFFAOYSA-N 0.000 description 1
- ODLORMUGIYVEGN-UHFFFAOYSA-N CC(C)N(CC1)CCN1C(N(C=C(C(c1c2)=NN3c4ccccn4)C3=O)c1cc(F)c2F)=O Chemical compound CC(C)N(CC1)CCN1C(N(C=C(C(c1c2)=NN3c4ccccn4)C3=O)c1cc(F)c2F)=O ODLORMUGIYVEGN-UHFFFAOYSA-N 0.000 description 1
- NOKHEHFYTNFBEL-UHFFFAOYSA-N CCC1=CCCC=C1 Chemical compound CCC1=CCCC=C1 NOKHEHFYTNFBEL-UHFFFAOYSA-N 0.000 description 1
- SKHXZXPLJNYYIU-UHFFFAOYSA-N CCOC(c(c(C)nc(cc1F)c2cc1F)c2Cl)=O Chemical compound CCOC(c(c(C)nc(cc1F)c2cc1F)c2Cl)=O SKHXZXPLJNYYIU-UHFFFAOYSA-N 0.000 description 1
- KFVBNISUOMPEAX-UHFFFAOYSA-N CN(C)C(N(C(CCCC1)C1C1N2C3CC=CCC3)C=C1C2O)O Chemical compound CN(C)C(N(C(CCCC1)C1C1N2C3CC=CCC3)C=C1C2O)O KFVBNISUOMPEAX-UHFFFAOYSA-N 0.000 description 1
- AVOSTZQDAFMQIG-UHFFFAOYSA-N COc1ccc(C(C(C2=O)=CN3)=NN2c2ccccc2)c3c1 Chemical compound COc1ccc(C(C(C2=O)=CN3)=NN2c2ccccc2)c3c1 AVOSTZQDAFMQIG-UHFFFAOYSA-N 0.000 description 1
- KGLIXBRZTAFTPH-UHTKEHJDSA-N C[C@@H](CCC=C1c2c3)C(Cc4ccccc4)C(C)C1=CN(C(N(CC1)CCN1c1ccccc1)=O)c2ccc3F Chemical compound C[C@@H](CCC=C1c2c3)C(Cc4ccccc4)C(C)C1=CN(C(N(CC1)CCN1c1ccccc1)=O)c2ccc3F KGLIXBRZTAFTPH-UHTKEHJDSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- VSBZUWCMCQATPV-UHFFFAOYSA-N Cc(cc(C(C1=CN2C(N(CC3)CCC3O)=O)=NN(c3c[s]cc3)C1=O)c2c1)c1F Chemical compound Cc(cc(C(C1=CN2C(N(CC3)CCC3O)=O)=NN(c3c[s]cc3)C1=O)c2c1)c1F VSBZUWCMCQATPV-UHFFFAOYSA-N 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 206010010904 Convulsion 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
- DCXXMTOCNZCJGO-UHFFFAOYSA-N Glycerol trioctadecanoate Natural products CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 206010019196 Head injury Diseases 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
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 108090000543 Ligand-Gated Ion Channels Proteins 0.000 description 1
- 102000004086 Ligand-Gated Ion Channels Human genes 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita 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
- 241000238367 Mya arenaria 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
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 1
- 229910003251 Na K Inorganic materials 0.000 description 1
- KIOCQMKEHORHQN-UHFFFAOYSA-N O=C(N1CCCCC1)N(C1C=CC=CC1C1=NN2c3ccccc3)C=C1C2=O Chemical compound O=C(N1CCCCC1)N(C1C=CC=CC1C1=NN2c3ccccc3)C=C1C2=O KIOCQMKEHORHQN-UHFFFAOYSA-N 0.000 description 1
- RKYFRHRGWRGZII-UHFFFAOYSA-N O=C1C2=C(C)NC3=CC=CC=C3C2=NN1C1=CC=CC=C1 Chemical compound O=C1C2=C(C)NC3=CC=CC=C3C2=NN1C1=CC=CC=C1 RKYFRHRGWRGZII-UHFFFAOYSA-N 0.000 description 1
- LZPRPSSMVKYQFX-UHFFFAOYSA-N O=C1N(c2ccccc2)N=C2c(cc(cc3)F)c3NC=C12 Chemical compound O=C1N(c2ccccc2)N=C2c(cc(cc3)F)c3NC=C12 LZPRPSSMVKYQFX-UHFFFAOYSA-N 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
- 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
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 101710137500 T7 RNA polymerase Proteins 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- FGEASBKBMNLZQR-UHFFFAOYSA-N [C].[O].[O] Chemical compound [C].[O].[O] FGEASBKBMNLZQR-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
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000443 aerosol 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
- 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
- 150000001340 alkali metals 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
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- 125000003277 amino group Chemical group 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
- 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
- 229940005530 anxiolytics Drugs 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
- 230000009901 attention process Effects 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
- 230000008901 benefit 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
- 239000011230 binding agent Substances 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- GUJMUFSJFDQBJC-UHFFFAOYSA-N bis(trichloromethyl) carbonate;carbonyl dichloride Chemical compound ClC(Cl)=O.ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl GUJMUFSJFDQBJC-UHFFFAOYSA-N 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000005388 borosilicate glass Substances 0.000 description 1
- 125000001246 bromo group Chemical group Br* 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
- 150000001669 calcium Chemical class 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- XTYGFVVANLMBHE-UHFFFAOYSA-N cgs-8216 Chemical compound N1C(C2=CC=CC=C2N=C2)=C2C(=O)N1C1=CC=CC=C1 XTYGFVVANLMBHE-UHFFFAOYSA-N 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 235000019693 cherries Nutrition 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 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
- 230000036992 cognitive tasks Effects 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 239000003179 convulsant agent Substances 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 230000007585 cortical function Effects 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
- 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
- PYPCDUKQEIPHAF-UHFFFAOYSA-N diethyl 2-(anilinomethylidene)propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)=CNC1=CC=CC=C1 PYPCDUKQEIPHAF-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 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
- 230000007831 electrophysiology Effects 0.000 description 1
- 238000002001 electrophysiology Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- PHRRSYMXOIKRAW-UHFFFAOYSA-N ethyl 2-methyl-4-oxo-1h-quinoline-3-carboxylate Chemical compound C1=CC=C2C(=O)C(C(=O)OCC)=C(C)NC2=C1 PHRRSYMXOIKRAW-UHFFFAOYSA-N 0.000 description 1
- UASKCSYIRXPZPX-UHFFFAOYSA-N ethyl 4-chloro-2-methylquinoline-3-carboxylate Chemical compound C1=CC=CC2=C(Cl)C(C(=O)OCC)=C(C)N=C21 UASKCSYIRXPZPX-UHFFFAOYSA-N 0.000 description 1
- 239000000374 eutectic mixture Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 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
- 230000003325 follicular Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 210000005153 frontal cortex Anatomy 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
- 230000005484 gravity Effects 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 238000010438 heat treatment Methods 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
- 230000008801 hippocampal function Effects 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo 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
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 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
- 230000003902 lesion Effects 0.000 description 1
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- NCBZRJODKRCREW-UHFFFAOYSA-N m-anisidine Chemical compound COC1=CC=CC(N)=C1 NCBZRJODKRCREW-UHFFFAOYSA-N 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000002609 medium Substances 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
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000009149 molecular binding Effects 0.000 description 1
- 230000008450 motivation Effects 0.000 description 1
- MLACQEBQGUBHKX-UHFFFAOYSA-N n,n-dimethylpiperidin-1-amine Chemical compound CN(C)N1CCCCC1 MLACQEBQGUBHKX-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
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 238000002610 neuroimaging Methods 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000007968 orange flavor Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000008188 pellet 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
- 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
- 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
- 229920001592 potato starch Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002335 preservative effect 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
- 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
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 238000000159 protein binding assay Methods 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
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-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
- 230000008707 rearrangement Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000002787 reinforcement Effects 0.000 description 1
- 230000002441 reversible effect 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
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- FNXKBSAUKFCXIK-UHFFFAOYSA-M sodium;hydrogen carbonate;8-hydroxy-7-iodoquinoline-5-sulfonic acid Chemical class [Na+].OC([O-])=O.C1=CN=C2C(O)=C(I)C=C(S(O)(=O)=O)C2=C1 FNXKBSAUKFCXIK-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
- 125000003003 spiro group Chemical group 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 238000007920 subcutaneous administration 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
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 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
- 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
- 238000011870 unpaired t-test Methods 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000009637 wintergreen oil Substances 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
- 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 (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US94299207P | 2007-06-08 | 2007-06-08 | |
| PCT/US2008/066205 WO2008154442A1 (en) | 2007-06-08 | 2008-06-06 | Therapeutic pyrazoloquinoline urea derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2010529144A true JP2010529144A (ja) | 2010-08-26 |
| JP2010529144A5 JP2010529144A5 (enExample) | 2011-07-14 |
Family
ID=40096439
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010511389A Pending JP2010529144A (ja) | 2007-06-08 | 2008-06-06 | 治療用ピラゾロキノリン尿素誘導体 |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US7863266B2 (enExample) |
| EP (1) | EP2164328B8 (enExample) |
| JP (1) | JP2010529144A (enExample) |
| KR (1) | KR20100038189A (enExample) |
| CN (1) | CN101686682A (enExample) |
| AU (1) | AU2008261888A1 (enExample) |
| BR (1) | BRPI0812347A2 (enExample) |
| CA (1) | CA2688405A1 (enExample) |
| ES (1) | ES2433566T3 (enExample) |
| IL (1) | IL202286A0 (enExample) |
| MX (1) | MX2009013205A (enExample) |
| WO (1) | WO2008154442A1 (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8927546B2 (en) * | 2006-02-28 | 2015-01-06 | Dart Neuroscience (Cayman) Ltd. | Therapeutic piperazines |
| US7863266B2 (en) * | 2007-06-08 | 2011-01-04 | Helicon Therapeutics, Inc. | Therapeutic pyrazoloquinoline urea derivatives |
| EP2490692B1 (en) * | 2009-10-21 | 2016-11-16 | Merck Sharp & Dohme Corp. | Quinolinone-pyrazolone m1 receptor positive allosteric modulators |
| US9468662B2 (en) | 2010-07-12 | 2016-10-18 | Orphit | Use of the PAT nonapeptide in the treatment and prevention of neurodegenerative diseases |
| FR2962335B1 (fr) * | 2010-07-12 | 2013-01-18 | Cll Pharma | Utilisation du nonapeptide pat dans le traitement et la prevention des maladies neurodegeneratives |
| US20150374705A1 (en) | 2012-02-14 | 2015-12-31 | Shanghai Institues for Biological Sciences | Substances for treatment or relief of pain |
| CN106187887B (zh) * | 2016-07-01 | 2018-08-14 | 上海工程技术大学 | 4-羟基喹啉-3-甲酸的制备方法 |
| PL3538512T3 (pl) | 2016-11-11 | 2021-11-22 | Bayer Animal Health Gmbh | Nowe pochodne chinolino-3-karboksyamidu o działaniu przeciw robakom pasożytniczym |
Citations (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5618980A (en) * | 1979-06-21 | 1981-02-23 | Ciba Geigy Ag | Pyrazoloquinone* manufacture* pharmaceutic medicine containing same and therapeutic application |
| JPS59110694A (ja) * | 1982-12-08 | 1984-06-26 | チバ−ガイギ−・アクチエンゲゼルシヤフト | 置換ピラゾロキノリン及びその製造方法並びに該化合物を含有する医薬 |
| 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 |
| US4814450A (en) * | 1984-07-09 | 1989-03-21 | Ciba-Geigy Corporation | Certain ring-fused pyrazolo[3,4-d]-pyridin-3-one derivatives |
| WO1992022552A1 (en) * | 1991-06-14 | 1992-12-23 | The Upjohn Company | IMIDAZO[1,5-a]QUINOXALINES |
| WO1997033889A1 (en) * | 1996-03-13 | 1997-09-18 | Neurogen Corporation | NOVEL IMIDAZO[1,5-c]QUINAZOLINES; A NEW CLASS OF GABA BRAIN RECEPTOR LIGANDS |
| WO1999006400A1 (en) * | 1997-08-01 | 1999-02-11 | Merck Sharp & Dohme Limited | Pyrazoloquinolinone derivatives as gaba alpha 5 receptor inverse agonists |
| WO1999006399A1 (en) * | 1997-08-01 | 1999-02-11 | Merck Sharp & Dohme Limited | Aryl-substituted pyrazoloquinolinone derivatives as gaba alpha 5 receptor inverse agonists |
| WO1999006401A1 (en) * | 1997-08-01 | 1999-02-11 | Merck Sharp & Dohme Limited | 2-ARYL-2,5-DIHYDRO-PYRAZOLO[4,3-c]QUINOLIN-3-ONES AS GABA ALPHA 5 RECEPTOR INVERSE AGONISTS |
| JP2004518748A (ja) * | 2001-02-21 | 2004-06-24 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 抗うつ薬としてのイソキサゾリン誘導体 |
| US20050245563A1 (en) * | 2003-05-29 | 2005-11-03 | Millennium Pharmaceuticals, Inc. | Chk-1 inhibitors |
| US20060035919A1 (en) * | 2002-12-16 | 2006-02-16 | Matthews Lan R | Tetracylic immunomodulatory compounds |
| WO2007049532A1 (ja) * | 2005-10-25 | 2007-05-03 | Shionogi & Co., Ltd. | アミノジヒドロチアジン誘導体 |
| JP2010529145A (ja) * | 2007-06-08 | 2010-08-26 | ヘリコン・セラピューティクス・インコーポレーテッド | 治療用ピラゾロナフチリジン誘導体 |
| JP2010529143A (ja) * | 2007-06-08 | 2010-08-26 | ヘリコン・セラピューティクス・インコーポレーテッド | 治療用ピラゾロキノリン誘導体 |
Family Cites Families (8)
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| US7863266B2 (en) * | 2007-06-08 | 2011-01-04 | Helicon Therapeutics, Inc. | Therapeutic pyrazoloquinoline urea derivatives |
-
2008
- 2008-06-06 US US12/135,023 patent/US7863266B2/en not_active Expired - Fee Related
- 2008-06-06 EP EP08770406.0A patent/EP2164328B8/en not_active Not-in-force
- 2008-06-06 CA CA002688405A patent/CA2688405A1/en not_active Abandoned
- 2008-06-06 JP JP2010511389A patent/JP2010529144A/ja active Pending
- 2008-06-06 WO PCT/US2008/066205 patent/WO2008154442A1/en not_active Ceased
- 2008-06-06 BR BRPI0812347A patent/BRPI0812347A2/pt not_active IP Right Cessation
- 2008-06-06 CN CN200880023876A patent/CN101686682A/zh active Pending
- 2008-06-06 ES ES08770406T patent/ES2433566T3/es active Active
- 2008-06-06 AU AU2008261888A patent/AU2008261888A1/en not_active Abandoned
- 2008-06-06 KR KR1020107000233A patent/KR20100038189A/ko not_active Withdrawn
- 2008-06-06 MX MX2009013205A patent/MX2009013205A/es active IP Right Grant
-
2009
- 2009-11-23 IL IL202286A patent/IL202286A0/en unknown
-
2010
- 2010-11-29 US US12/955,792 patent/US8343957B2/en not_active Expired - Fee Related
Patent Citations (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5618980A (en) * | 1979-06-21 | 1981-02-23 | Ciba Geigy Ag | Pyrazoloquinone* manufacture* pharmaceutic medicine containing same and therapeutic application |
| JPS59110694A (ja) * | 1982-12-08 | 1984-06-26 | チバ−ガイギ−・アクチエンゲゼルシヤフト | 置換ピラゾロキノリン及びその製造方法並びに該化合物を含有する医薬 |
| 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 |
| WO1992022552A1 (en) * | 1991-06-14 | 1992-12-23 | The Upjohn Company | IMIDAZO[1,5-a]QUINOXALINES |
| WO1997033889A1 (en) * | 1996-03-13 | 1997-09-18 | Neurogen Corporation | NOVEL IMIDAZO[1,5-c]QUINAZOLINES; A NEW CLASS OF GABA BRAIN RECEPTOR LIGANDS |
| WO1999006400A1 (en) * | 1997-08-01 | 1999-02-11 | Merck Sharp & Dohme Limited | Pyrazoloquinolinone derivatives as gaba alpha 5 receptor inverse agonists |
| WO1999006399A1 (en) * | 1997-08-01 | 1999-02-11 | Merck Sharp & Dohme Limited | Aryl-substituted pyrazoloquinolinone derivatives as gaba alpha 5 receptor inverse agonists |
| WO1999006401A1 (en) * | 1997-08-01 | 1999-02-11 | Merck Sharp & Dohme Limited | 2-ARYL-2,5-DIHYDRO-PYRAZOLO[4,3-c]QUINOLIN-3-ONES AS GABA ALPHA 5 RECEPTOR INVERSE AGONISTS |
| JP2004518748A (ja) * | 2001-02-21 | 2004-06-24 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 抗うつ薬としてのイソキサゾリン誘導体 |
| US20060035919A1 (en) * | 2002-12-16 | 2006-02-16 | Matthews Lan R | Tetracylic immunomodulatory compounds |
| US20050245563A1 (en) * | 2003-05-29 | 2005-11-03 | Millennium Pharmaceuticals, Inc. | Chk-1 inhibitors |
| WO2007049532A1 (ja) * | 2005-10-25 | 2007-05-03 | Shionogi & Co., Ltd. | アミノジヒドロチアジン誘導体 |
| JP2010529145A (ja) * | 2007-06-08 | 2010-08-26 | ヘリコン・セラピューティクス・インコーポレーテッド | 治療用ピラゾロナフチリジン誘導体 |
| JP2010529143A (ja) * | 2007-06-08 | 2010-08-26 | ヘリコン・セラピューティクス・インコーポレーテッド | 治療用ピラゾロキノリン誘導体 |
Non-Patent Citations (1)
| Title |
|---|
| JPN6013016434; Ｊｏｕｒｎａｌ ｏｆ Ｍｅｄｉｃｉｎａｌ Ｃｈｅｍｉｓｔｒｙ ４２（７）, 1999, １１２３-１１４４ * |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2164328B1 (en) | 2013-08-07 |
| EP2164328B8 (en) | 2013-09-11 |
| CN101686682A (zh) | 2010-03-31 |
| CA2688405A1 (en) | 2008-12-18 |
| EP2164328A4 (en) | 2010-06-23 |
| BRPI0812347A2 (pt) | 2016-08-02 |
| HK1142496A1 (en) | 2010-12-10 |
| IL202286A0 (en) | 2010-06-16 |
| MX2009013205A (es) | 2010-04-09 |
| US20110071140A1 (en) | 2011-03-24 |
| KR20100038189A (ko) | 2010-04-13 |
| AU2008261888A1 (en) | 2008-12-18 |
| ES2433566T3 (es) | 2013-12-11 |
| US8343957B2 (en) | 2013-01-01 |
| US7863266B2 (en) | 2011-01-04 |
| EP2164328A1 (en) | 2010-03-24 |
| US20080306048A1 (en) | 2008-12-11 |
| WO2008154442A1 (en) | 2008-12-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8343957B2 (en) | Therapeutic pyrazoloquinoline urea derivatives | |
| US8598159B2 (en) | Therapeutic pyrazoloquinoline derivatives | |
| US8497262B2 (en) | Therapeutic pyrazolonaphthyridine derivatives | |
| JP2010529145A5 (enExample) | ||
| HK1142776A (en) | Therapeutic pyrazoloquinoline urea derivatives | |
| HK1142496B (en) | Therapeutic pyrazoloquinoline urea derivatives | |
| HK1144891A (zh) | 治疗用吡唑并喹啉衍生物 | |
| HK1142775B (en) | Therapeutic pyrazoloquinoline derivatives | |
| US9012470B2 (en) | Therapeutic 5,6,5-tricyclic analogs | |
| HK1144892A (en) | Therapeutic pyrazolonaphthyridine derivatives | |
| HK1142774B (en) | Therapeutic pyrazolonaphthyridine derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100527 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110525 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20110525 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130409 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20130910 |