KR20170032420A - Pde 억제제로서의 신규한 2,5-치환된 피리미딘 - Google Patents
Pde 억제제로서의 신규한 2,5-치환된 피리미딘 Download PDFInfo
- Publication number
- KR20170032420A KR20170032420A KR1020177004411A KR20177004411A KR20170032420A KR 20170032420 A KR20170032420 A KR 20170032420A KR 1020177004411 A KR1020177004411 A KR 1020177004411A KR 20177004411 A KR20177004411 A KR 20177004411A KR 20170032420 A KR20170032420 A KR 20170032420A
- Authority
- KR
- South Korea
- Prior art keywords
- alkyl
- alkylene
- yield
- pyrimidin
- mmol
- 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- Withdrawn
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- 150000003230 pyrimidines Chemical class 0.000 title claims abstract description 13
- 239000003112 inhibitor Substances 0.000 title description 4
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 18
- 102000004190 Enzymes Human genes 0.000 claims abstract description 12
- 108090000790 Enzymes Proteins 0.000 claims abstract description 12
- 230000005764 inhibitory process Effects 0.000 claims abstract description 12
- 101100296720 Dictyostelium discoideum Pde4 gene Proteins 0.000 claims abstract 2
- 101100082610 Plasmodium falciparum (isolate 3D7) PDEdelta gene Proteins 0.000 claims abstract 2
- -1 N-pyrrolidinyl Chemical group 0.000 claims description 450
- 238000000034 method Methods 0.000 claims description 390
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 358
- 239000000203 mixture Substances 0.000 claims description 97
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 48
- 125000001424 substituent group Chemical group 0.000 claims description 44
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 40
- 229910052739 hydrogen Inorganic materials 0.000 claims description 40
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 37
- 229910052757 nitrogen Chemical group 0.000 claims description 37
- 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 claims description 30
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 27
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 23
- 239000001257 hydrogen Substances 0.000 claims description 22
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
- 239000002253 acid Substances 0.000 claims description 20
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 20
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 18
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 18
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 15
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- 229910052736 halogen Inorganic materials 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 14
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- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 12
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 10
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 10
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- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 8
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 8
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims description 8
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
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- 125000002619 bicyclic group Chemical group 0.000 claims description 7
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- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 4
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- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 3
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- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
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- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 2
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Classifications
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| PCT/EP2015/001475 WO2016008592A1 (en) | 2014-07-16 | 2015-07-16 | Novel 2,5-substituted pyrimidines as pde inhibitors |
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| MX2018010192A (es) * | 2016-02-25 | 2019-01-31 | Asceneuron S A | Inhibidores de glucosidasa. |
| CN108570052A (zh) * | 2017-03-13 | 2018-09-25 | 中国科学院上海药物研究所 | 五元杂环并吡嗪化合物、制备方法、中间体、组合和应用 |
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| WO2018234353A1 (en) | 2017-06-20 | 2018-12-27 | Grünenthal GmbH | Novel substituted indole and indazole compounds as phosphodiesterase inhibitors |
| CN119954804B (zh) * | 2025-04-10 | 2025-08-12 | 广州呼吸药物工程技术有限公司 | 嘧啶并[6,1-a]异喹啉-4-酮衍生物及其用途 |
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| US7087597B1 (en) * | 1999-10-12 | 2006-08-08 | Takeda Pharmaceutical Company Limited | Pyrimidine 5-carboxamide compounds, process for producing the same and use thereof |
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| NZ567133A (en) * | 2005-09-30 | 2011-07-29 | Vertex Pharma | Deazapurines useful as inhibitors of janus kinases |
| TW201512189A (zh) | 2013-04-16 | 2015-04-01 | Gruenenthal Chemie | 新型被取代之嘧啶縮合化合物 |
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| US9315490B2 (en) | 2016-04-19 |
| AU2015291477B2 (en) | 2019-02-21 |
| TW201609708A (zh) | 2016-03-16 |
| EP3169680A1 (en) | 2017-05-24 |
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| JP2017520600A (ja) | 2017-07-27 |
| JP6726655B2 (ja) | 2020-07-22 |
| CO2017001523A2 (es) | 2017-05-10 |
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