KR20100038189A - 치료적 피라졸로퀴놀린 우레아 유도체 - Google Patents
치료적 피라졸로퀴놀린 우레아 유도체Info
- Publication number
- KR20100038189A KR20100038189A KR1020107000233A KR20107000233A KR20100038189A KR 20100038189 A KR20100038189 A KR 20100038189A KR 1020107000233 A KR1020107000233 A KR 1020107000233A KR 20107000233 A KR20107000233 A KR 20107000233A KR 20100038189 A KR20100038189 A KR 20100038189A
- Authority
- KR
- South Korea
- Prior art keywords
- formula
- compound
- alkyl
- pharmaceutically acceptable
- acceptable salt
- 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.)
- Withdrawn
Links
- 230000001225 therapeutic effect Effects 0.000 title description 2
- 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 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 206
- 238000000034 method Methods 0.000 claims abstract description 115
- 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 52
- 229960003692 gamma aminobutyric acid Drugs 0.000 claims abstract description 50
- 239000003814 drug Substances 0.000 claims abstract description 18
- 238000004519 manufacturing process Methods 0.000 claims abstract description 14
- 150000003839 salts Chemical class 0.000 claims description 82
- 125000003118 aryl group Chemical group 0.000 claims description 66
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 64
- 229910052739 hydrogen Inorganic materials 0.000 claims description 57
- 125000001153 fluoro group Chemical group F* 0.000 claims description 54
- 239000001257 hydrogen Substances 0.000 claims description 45
- 125000000623 heterocyclic group Chemical group 0.000 claims description 35
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 27
- 230000015654 memory Effects 0.000 claims description 26
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
- -1 —NR a R b Chemical group 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
- 239000000203 mixture Substances 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 18
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 18
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 17
- 208000010877 cognitive disease Diseases 0.000 claims description 17
- 229910052760 oxygen Inorganic materials 0.000 claims description 17
- 239000001301 oxygen Substances 0.000 claims description 17
- 230000033228 biological regulation Effects 0.000 claims description 10
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 8
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 8
- 230000003920 cognitive function Effects 0.000 claims description 8
- 208000024827 Alzheimer disease Diseases 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 6
- 230000007787 long-term memory Effects 0.000 claims description 6
- 125000004043 oxo group Chemical group O=* 0.000 claims description 6
- 230000001105 regulatory effect Effects 0.000 claims description 6
- 125000002757 morpholinyl group Chemical group 0.000 claims description 5
- 208000020016 psychiatric disease Diseases 0.000 claims description 5
- 201000000980 schizophrenia Diseases 0.000 claims description 5
- 230000006403 short-term memory Effects 0.000 claims description 5
- 208000019901 Anxiety disease Diseases 0.000 claims description 4
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 4
- 230000004770 neurodegeneration Effects 0.000 claims description 4
- 208000015122 neurodegenerative disease Diseases 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
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 4
- 208000035475 disorder Diseases 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 208000019116 sleep disease Diseases 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
- 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
- 229940049706 benzodiazepine Drugs 0.000 abstract description 7
- 230000027455 binding Effects 0.000 abstract description 7
- 239000000126 substance Substances 0.000 abstract description 5
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 abstract description 4
- 102000005915 GABA Receptors Human genes 0.000 abstract description 3
- 108010005551 GABA Receptors Proteins 0.000 abstract description 3
- 229910052740 iodine Inorganic materials 0.000 abstract description 2
- 230000008569 process Effects 0.000 description 73
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
- 230000015572 biosynthetic process Effects 0.000 description 38
- 238000003786 synthesis reaction Methods 0.000 description 37
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 32
- 239000000243 solution Substances 0.000 description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 20
- 238000012549 training Methods 0.000 description 20
- WHKWMTXTYKVFLK-UHFFFAOYSA-N 1-propan-2-ylpiperazine Chemical compound CC(C)N1CCNCC1 WHKWMTXTYKVFLK-UHFFFAOYSA-N 0.000 description 18
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- UZOFELREXGAFOI-UHFFFAOYSA-N 4-methylpiperidine Chemical compound CC1CCNCC1 UZOFELREXGAFOI-UHFFFAOYSA-N 0.000 description 16
- 102000005962 receptors Human genes 0.000 description 16
- 108020003175 receptors Proteins 0.000 description 16
- 239000002904 solvent Substances 0.000 description 16
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 150000003254 radicals Chemical class 0.000 description 12
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical group CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 11
- 210000000287 oocyte Anatomy 0.000 description 11
- 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
- 125000004122 cyclic group Chemical group 0.000 description 10
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 239000007788 liquid Substances 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
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 9
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 125000005842 heteroatom Chemical group 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-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
- 238000002360 preparation method Methods 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000012320 chlorinating reagent Substances 0.000 description 6
- 239000002299 complementary DNA Substances 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 description 5
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 5
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 239000004202 carbamide Substances 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 239000000460 chlorine Substances 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
- 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
- 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 4
- 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 4
- 241000282412 Homo Species 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 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
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 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
- 239000002775 capsule Substances 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 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 4
- LTMHNWPUDSTBKD-UHFFFAOYSA-N diethyl 2-(ethoxymethylidene)propanedioate Chemical compound CCOC=C(C(=O)OCC)C(=O)OCC LTMHNWPUDSTBKD-UHFFFAOYSA-N 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
- 201000010099 disease Diseases 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 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 4
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 4
- 229940093858 ethyl acetoacetate Drugs 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 229940078552 o-xylene Drugs 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
- 238000003756 stirring Methods 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
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- 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 3
- 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
- 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 3
- 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 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
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
- 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 3
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Classifications
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- 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
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- 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 | |
| US60/942,992 | 2007-06-08 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20100038189A true KR20100038189A (ko) | 2010-04-13 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020107000233A Withdrawn KR20100038189A (ko) | 2007-06-08 | 2008-06-06 | 치료적 피라졸로퀴놀린 우레아 유도체 |
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| 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 |
Family Cites Families (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3068673D1 (en) * | 1979-06-21 | 1984-08-30 | Ciba Geigy Ag | Pyrazolo-quinolines, processes for their production, and pharmaceutical compositions containing them |
| DE3204126A1 (de) | 1982-02-06 | 1983-08-11 | Bayer Ag, 5090 Leverkusen | Pyrazoloxazine, -thiazine, -chinoline, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
| US4524146A (en) * | 1982-12-08 | 1985-06-18 | Ciba-Geigy Corporation | Certain -2-heterocycle substituted pyrazoloquinolines |
| US4814450A (en) * | 1984-07-09 | 1989-03-21 | Ciba-Geigy Corporation | Certain ring-fused pyrazolo[3,4-d]-pyridin-3-one derivatives |
| JPS61112075A (ja) * | 1984-11-05 | 1986-05-30 | Shionogi & Co Ltd | チエニルピラゾロキノリン誘導体 |
| EP0214092A1 (en) | 1985-08-08 | 1987-03-11 | Ciba-Geigy Ag | Enhanced absorption of psychoactive 2-aryl-pyrazolo quinolines as a solid molecular dispersion in polyvinylpyrrolidone |
| WO1992022552A1 (en) * | 1991-06-14 | 1992-12-23 | The Upjohn Company | IMIDAZO[1,5-a]QUINOXALINES |
| US5334595A (en) | 1992-10-23 | 1994-08-02 | Sterling Winthrop Inc. | Pyrazoloquinolones as anticancer agents |
| US5792766A (en) * | 1996-03-13 | 1998-08-11 | Neurogen Corporation | Imidazo 1,5-c! quinazolines; a new class of GABA brain receptor ligands |
| GB9716345D0 (en) * | 1997-08-01 | 1997-10-08 | Merck Sharp & Dohme | Therapeutic compounds |
| GB9716344D0 (en) * | 1997-08-01 | 1997-10-08 | Merck Sharp & Dohme | Therapeutic compounds |
| GB9716347D0 (en) * | 1997-08-01 | 1997-10-08 | Merck Sharp & Dohme | Therapeutic compounds |
| TWI271406B (en) | 1999-12-13 | 2007-01-21 | Eisai Co Ltd | Tricyclic condensed heterocyclic compounds, preparation method of the same and pharmaceuticals comprising the same |
| HUP0303270A3 (en) * | 2001-02-21 | 2007-03-28 | Janssen Pharmaceutica Nv | Isoxazoline derivatives as anti-depressants, process for their preparation and pharmaceutical compositions containing them |
| JP3896309B2 (ja) | 2001-07-09 | 2007-03-22 | ファイザー株式会社 | プロテインキナーゼｃ阻害物質としてのピラゾロキノリノン誘導体 |
| ATE425164T1 (de) * | 2002-12-16 | 2009-03-15 | Active Biotech Ab | Tetrazyklische immunmodulierende verbindungen |
| AR045689A1 (es) * | 2003-05-29 | 2005-11-09 | Millennium Pharm Inc | Compuestos derivados de 2,5-dihidro-pirazolo[4,3-c]quinolin-4-ona como inhibidores de chk-1 y composiciones farmaceuticas que los contienen |
| US7544697B2 (en) | 2003-10-03 | 2009-06-09 | Coley Pharmaceutical Group, Inc. | Pyrazolopyridines and analogs thereof |
| AU2006287378A1 (en) | 2005-09-07 | 2007-03-15 | Braincells, Inc. | Modulation of neurogenesis by HDac inhibition |
| US8173642B2 (en) * | 2005-10-25 | 2012-05-08 | Shionogi & Co., Ltd. | Aminodihydrothiazine derivatives |
| ES2386168T3 (es) * | 2007-06-08 | 2012-08-10 | Helicon Therapeutics, Inc. | Derivados de pirazoloquinolina terapéuticos |
| US7863266B2 (en) * | 2007-06-08 | 2011-01-04 | Helicon Therapeutics, Inc. | Therapeutic pyrazoloquinoline urea derivatives |
| ES2483728T3 (es) * | 2007-06-08 | 2014-08-07 | Dart Neuroscience (Cayman) Ltd | Derivados terapéuticos de pirazolonafatiridina |
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2008
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- 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
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2009
- 2009-11-23 IL IL202286A patent/IL202286A0/en unknown
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2010
- 2010-11-29 US US12/955,792 patent/US8343957B2/en not_active Expired - Fee Related
Also Published As
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|---|---|
| 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 |
| JP2010529144A (ja) | 2010-08-26 |
| 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 |
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| PA0105 | International application |
Patent event date: 20100106 Patent event code: PA01051R01D Comment text: International Patent Application |
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| PC1203 | Withdrawal of no request for examination | ||
| WITN | Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid |