JP6608933B2 - 有機化合物 - Google Patents
有機化合物 Download PDFInfo
- Publication number
- JP6608933B2 JP6608933B2 JP2017530034A JP2017530034A JP6608933B2 JP 6608933 B2 JP6608933 B2 JP 6608933B2 JP 2017530034 A JP2017530034 A JP 2017530034A JP 2017530034 A JP2017530034 A JP 2017530034A JP 6608933 B2 JP6608933 B2 JP 6608933B2
- Authority
- JP
- Japan
- Prior art keywords
- pyrazolo
- methyl
- butoxy
- naphthyridin
- fluorophenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 150000002894 organic compounds Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 105
- -1 alkyl luma Chemical compound 0.000 claims description 64
- 125000000217 alkyl group Chemical group 0.000 claims description 46
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 31
- 101100135859 Dictyostelium discoideum regA gene Proteins 0.000 claims description 24
- 101100082606 Plasmodium falciparum (isolate 3D7) PDEbeta gene Proteins 0.000 claims description 24
- 101100135860 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) PDE2 gene Proteins 0.000 claims description 24
- 125000005843 halogen group Chemical group 0.000 claims description 22
- 150000003839 salts Chemical group 0.000 claims description 22
- 125000001153 fluoro group Chemical group F* 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 13
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- 239000003085 diluting agent Substances 0.000 claims description 9
- 208000028698 Cognitive impairment Diseases 0.000 claims description 8
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- 208000029560 autism spectrum disease Diseases 0.000 claims description 8
- 230000001404 mediated effect Effects 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 7
- KCZWAWIWVZBEHK-UHFFFAOYSA-N 1-(5-butoxy-2-fluorophenyl)-3-methyl-4-oxo-5H-pyrazolo[4,3-h][1,5]naphthyridine-8-carboxylic acid Chemical compound CCCCOC1=CC(N2N=C(C)C3=C2C2=C(NC3=O)C=CC(=N2)C(O)=O)=C(F)C=C1 KCZWAWIWVZBEHK-UHFFFAOYSA-N 0.000 claims description 6
- LZYZEOLAPLNPLJ-UHFFFAOYSA-N 1-(5-butoxy-2-fluorophenyl)-3-methyl-4-oxo-5H-pyrazolo[4,3-h][1,5]naphthyridine-8-carbonitrile Chemical compound CCCCOC1=CC(N2N=C(C)C3=C2C2=C(NC3=O)C=CC(=N2)C#N)=C(F)C=C1 LZYZEOLAPLNPLJ-UHFFFAOYSA-N 0.000 claims description 5
- GAJCDBSBYDXXKD-UHFFFAOYSA-N 1-(5-butoxy-2-fluorophenyl)-N-ethyl-3-methyl-4-oxo-5H-pyrazolo[4,3-h][1,5]naphthyridine-8-carboxamide Chemical compound CCCCOC1=CC(N2N=C(C)C3=C2C2=C(NC3=O)C=CC(=N2)C(=O)NCC)=C(F)C=C1 GAJCDBSBYDXXKD-UHFFFAOYSA-N 0.000 claims description 5
- VFCZPATWIYOHJQ-UHFFFAOYSA-N 1-(2,5-dichlorophenyl)-3-methyl-5H-pyrazolo[4,3-c][1,5]naphthyridin-4-one Chemical compound CC1=NN(C2=C1C(=O)NC1=C2N=CC=C1)C1=C(Cl)C=CC(Cl)=C1 VFCZPATWIYOHJQ-UHFFFAOYSA-N 0.000 claims description 4
- CWYBEKQXIDZGCO-UHFFFAOYSA-N 1-(2-chlorophenyl)-3,5-dimethylpyrazolo[4,3-c][1,5]naphthyridin-4-one Chemical compound CN1C(=O)C2=C(N(N=C2C)C2=C(Cl)C=CC=C2)C2=C1C=CC=N2 CWYBEKQXIDZGCO-UHFFFAOYSA-N 0.000 claims description 4
- WQYNZBWUUFOYLZ-UHFFFAOYSA-N 1-(2-chlorophenyl)-3-methyl-5H-pyrazolo[4,3-c][1,5]naphthyridin-4-one Chemical compound CC1=NN(C2=C1C(=O)NC1=C2N=CC=C1)C1=C(Cl)C=CC=C1 WQYNZBWUUFOYLZ-UHFFFAOYSA-N 0.000 claims description 4
- HLMDAEZBEKMIQP-UHFFFAOYSA-N 1-(5-butoxy-2-chlorophenyl)-8-chloro-3-methyl-3,3a,5,5a,6,7,8,9,9a,9b-decahydro-2H-pyrazolo[4,3-c][1,5]naphthyridin-4-one Chemical compound CCCCOc1ccc(Cl)c(c1)N1NC(C)C2C1C1NC(Cl)CCC1NC2=O HLMDAEZBEKMIQP-UHFFFAOYSA-N 0.000 claims description 4
- CBGSELCUTQWMFO-UHFFFAOYSA-N 1-(5-butoxy-2-chlorophenyl)-8-methoxy-3-methyl-3,3a,5,5a,6,7,8,9,9a,9b-decahydro-2H-pyrazolo[4,3-c][1,5]naphthyridin-4-one Chemical compound CCCCOc1ccc(Cl)c(c1)N1NC(C)C2C1C1NC(CCC1NC2=O)OC CBGSELCUTQWMFO-UHFFFAOYSA-N 0.000 claims description 4
- QDJBJYWUERRLGN-UHFFFAOYSA-N 1-(5-butoxy-2-fluorophenyl)-3-methyl-4-oxo-3aH-pyrazolo[4,3-h][1,5]naphthyridine-8-carboxamide Chemical compound CCCCOC1=CC(N2N=C(C)C3C2=C2N=C(C=CC2=NC3=O)C(N)=O)=C(F)C=C1 QDJBJYWUERRLGN-UHFFFAOYSA-N 0.000 claims description 4
- OYJBYVZPNLLRDF-UHFFFAOYSA-N 1-(5-butoxy-2-fluorophenyl)-8-(4-fluorophenoxy)-3-methyl-5H-pyrazolo[4,3-c][1,5]naphthyridin-4-one Chemical compound CCCCOC1=CC(N2N=C(C)C3=C2C2=C(NC3=O)C=CC(OC3=CC=C(F)C=C3)=N2)=C(F)C=C1 OYJBYVZPNLLRDF-UHFFFAOYSA-N 0.000 claims description 4
- FVKTYFNDUDJLCL-UHFFFAOYSA-N 1-[2-chloro-5-(cyclobutylmethoxy)phenyl]-8-methoxy-3-methyl-3,3a,5,5a,6,7,8,9,9a,9b-decahydro-2H-pyrazolo[4,3-c][1,5]naphthyridin-4-one Chemical compound COC1CCC2NC(=O)C3C(C)NN(C3C2N1)c1cc(OCC2CCC2)ccc1Cl FVKTYFNDUDJLCL-UHFFFAOYSA-N 0.000 claims description 4
- LUJYZELYBGDWBN-UHFFFAOYSA-N 8-chloro-1-[2-chloro-5-(cyclopropylmethoxy)phenyl]-3-methyl-5H-pyrazolo[4,3-c][1,5]naphthyridin-4-one Chemical compound CC1=NN(C2=C1C(=O)NC1=C2N=C(Cl)C=C1)C1=C(Cl)C=CC(OCC2CC2)=C1 LUJYZELYBGDWBN-UHFFFAOYSA-N 0.000 claims description 4
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- TXMNAVBOXBRWRL-UHFFFAOYSA-N 1-(2,5-dichlorophenyl)-3,5-dimethylpyrazolo[4,3-c][1,5]naphthyridin-4-one Chemical compound CN1C(=O)C2=C(N(N=C2C)C2=C(Cl)C=CC(Cl)=C2)C2=C1C=CC=N2 TXMNAVBOXBRWRL-UHFFFAOYSA-N 0.000 claims description 3
- KSGXFQJHUNDYRZ-UHFFFAOYSA-N 1-(5-butoxy-2-chlorophenyl)-3-methyl-3,3a,5,5a,6,7,8,9,9a,9b-decahydro-2H-pyrazolo[4,3-c][1,5]naphthyridin-4-one Chemical compound CCCCOc1ccc(Cl)c(c1)N1NC(C)C2C1C1NCCCC1NC2=O KSGXFQJHUNDYRZ-UHFFFAOYSA-N 0.000 claims description 3
- GVCWNUHDYYGLHB-UHFFFAOYSA-N 1-(5-butoxy-2-fluorophenyl)-3-methyl-5H-pyrazolo[4,3-c][1,5]naphthyridin-4-one Chemical compound C(CCC)OC=1C=CC(=C(C=1)N1N=C(C=2C(NC=3C=CC=NC=3C=21)=O)C)F GVCWNUHDYYGLHB-UHFFFAOYSA-N 0.000 claims description 3
- SFIZQWYZYMPKTG-UHFFFAOYSA-N 1-(5-butoxy-2-fluorophenyl)-3-methyl-8-(pyridin-2-ylamino)-5H-pyrazolo[4,3-c][1,5]naphthyridin-4-one Chemical compound CCCCOC1=CC(N2N=C(C)C3=C2C2=C(NC3=O)C=CC(NC3=NC=CC=C3)=N2)=C(F)C=C1 SFIZQWYZYMPKTG-UHFFFAOYSA-N 0.000 claims description 3
- GEWLDLSFZCTLFZ-UHFFFAOYSA-N 1-(5-butoxy-2-fluorophenyl)-3-methyl-8-pyrazol-1-yl-5H-pyrazolo[4,3-c][1,5]naphthyridin-4-one Chemical compound CCCCOC1=CC(N2N=C(C)C3=C2C2=C(NC3=O)C=CC(=N2)N2C=CC=N2)=C(F)C=C1 GEWLDLSFZCTLFZ-UHFFFAOYSA-N 0.000 claims description 3
- HABNVWFXKMBDEC-UHFFFAOYSA-N 1-(5-butoxy-2-fluorophenyl)-3-methyl-8-pyrrolidin-1-yl-5H-pyrazolo[4,3-c][1,5]naphthyridin-4-one Chemical compound CCCCOC1=CC(N2N=C(C)C3=C2C2=C(NC3=O)C=CC(=N2)N2CCCC2)=C(F)C=C1 HABNVWFXKMBDEC-UHFFFAOYSA-N 0.000 claims description 3
- IMAOQPNOONDYGN-UHFFFAOYSA-N 1-(5-butoxy-2-fluorophenyl)-8-(dimethylamino)-3-methyl-5H-pyrazolo[4,3-c][1,5]naphthyridin-4-one Chemical compound C(CCC)OC=1C=CC(=C(C=1)N1N=C(C=2C(NC=3C=CC(=NC=3C=21)N(C)C)=O)C)F IMAOQPNOONDYGN-UHFFFAOYSA-N 0.000 claims description 3
- MXVWSDWPQOLZHX-UHFFFAOYSA-N 1-(5-butoxy-2-fluorophenyl)-8-ethylsulfanyl-3-methyl-5H-pyrazolo[4,3-c][1,5]naphthyridin-4-one Chemical compound C(CCC)OC=1C=CC(=C(C=1)N1N=C(C=2C(NC=3C=CC(=NC=3C=21)SCC)=O)C)F MXVWSDWPQOLZHX-UHFFFAOYSA-N 0.000 claims description 3
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- GHKSZQKFAPBQJP-UHFFFAOYSA-N 8-chloro-1-(2,5-dichlorophenyl)-3-methyl-3,3a,5,5a,6,7,8,9,9a,9b-decahydro-2H-pyrazolo[4,3-c][1,5]naphthyridin-4-one Chemical compound CC1NN(C2C1C(=O)NC1CCC(Cl)NC21)c1cc(Cl)ccc1Cl GHKSZQKFAPBQJP-UHFFFAOYSA-N 0.000 claims description 2
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- CSYSETGWAJKQLE-UHFFFAOYSA-N ethyl 1-(5-butoxy-2-fluorophenyl)-3-methyl-4-oxo-5H-pyrazolo[4,3-h][1,5]naphthyridine-8-carboxylate Chemical compound C(CCC)OC=1C=CC(=C(C=1)N1N=C(C=2C(NC=3C=CC(=NC=3C=21)C(=O)OCC)=O)C)F CSYSETGWAJKQLE-UHFFFAOYSA-N 0.000 claims description 2
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 125000001309 chloro group Chemical group Cl* 0.000 description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 21
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
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| US9628116B2 (en) | 2015-07-14 | 2017-04-18 | At&T Intellectual Property I, L.P. | Apparatus and methods for transmitting wireless signals |
| TWI795381B (zh) | 2016-12-21 | 2023-03-11 | 比利時商健生藥品公司 | 作為ｍａｌｔ１抑制劑之吡唑衍生物 |
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| MX2017007377A (es) | 2017-11-06 |
| CN107205993A (zh) | 2017-09-26 |
| CA2969597C (en) | 2023-10-24 |
| RU2702732C1 (ru) | 2019-10-10 |
| HK1244427A1 (zh) | 2018-08-10 |
| KR102562576B1 (ko) | 2023-08-01 |
| BR112017012005A2 (pt) | 2017-12-26 |
| EP3226862A4 (en) | 2018-05-09 |
| CA2969597A1 (en) | 2016-06-09 |
| US10105349B2 (en) | 2018-10-23 |
| WO2016090382A1 (en) | 2016-06-09 |
| US20190000807A1 (en) | 2019-01-03 |
| BR112017012005B1 (pt) | 2023-04-04 |
| HK1243935A1 (zh) | 2018-07-27 |
| MX373320B (es) | 2020-05-04 |
| CN107205993B (zh) | 2021-03-09 |
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