KR102457840B1 - 보론산 유도체 - Google Patents
보론산 유도체 Download PDFInfo
- Publication number
- KR102457840B1 KR102457840B1 KR1020177011562A KR20177011562A KR102457840B1 KR 102457840 B1 KR102457840 B1 KR 102457840B1 KR 1020177011562 A KR1020177011562 A KR 1020177011562A KR 20177011562 A KR20177011562 A KR 20177011562A KR 102457840 B1 KR102457840 B1 KR 102457840B1
- Authority
- KR
- South Korea
- Prior art keywords
- amino
- ethyl
- boronic acid
- acetyl
- prop
- 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.)
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- 150000001642 boronic acid derivatives Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 419
- 238000011282 treatment Methods 0.000 claims abstract description 21
- 101001136986 Homo sapiens Proteasome subunit beta type-8 Proteins 0.000 claims abstract description 14
- 102100035760 Proteasome subunit beta type-8 Human genes 0.000 claims abstract description 14
- 201000005787 hematologic cancer Diseases 0.000 claims abstract description 8
- -1 monocyclic hydrocarbon Chemical class 0.000 claims description 412
- 150000003839 salts Chemical class 0.000 claims description 99
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 71
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 63
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 60
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 54
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 51
- 125000001424 substituent group Chemical group 0.000 claims description 49
- 229910052739 hydrogen Inorganic materials 0.000 claims description 45
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 44
- 239000004480 active ingredient Substances 0.000 claims description 41
- 125000000623 heterocyclic group Chemical group 0.000 claims description 39
- 229910052799 carbon Inorganic materials 0.000 claims description 38
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 37
- 238000000034 method Methods 0.000 claims description 36
- 125000003118 aryl group Chemical group 0.000 claims description 34
- 229910052760 oxygen Inorganic materials 0.000 claims description 30
- 238000006467 substitution reaction Methods 0.000 claims description 29
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 26
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 25
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 23
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 21
- 125000004434 sulfur atom Chemical group 0.000 claims description 21
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 20
- 125000004122 cyclic group Chemical group 0.000 claims description 20
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 20
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 19
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 18
- 229930195733 hydrocarbon Natural products 0.000 claims description 18
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 17
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 17
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 17
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 17
- 239000004215 Carbon black (E152) Substances 0.000 claims description 16
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 16
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 16
- 150000001408 amides Chemical class 0.000 claims description 15
- 229920006395 saturated elastomer Polymers 0.000 claims description 15
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 15
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 14
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 10
- 230000002519 immonomodulatory effect Effects 0.000 claims description 10
- 230000005764 inhibitory process Effects 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 239000004305 biphenyl Substances 0.000 claims description 9
- 235000010290 biphenyl Nutrition 0.000 claims description 9
- 125000001624 naphthyl group Chemical group 0.000 claims description 9
- 229940124530 sulfonamide Drugs 0.000 claims description 9
- 150000003456 sulfonamides Chemical class 0.000 claims description 9
- 125000005620 boronic acid group Chemical group 0.000 claims description 7
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
- 230000002265 prevention Effects 0.000 claims description 7
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 7
- 150000002430 hydrocarbons Chemical class 0.000 claims description 6
- 125000002950 monocyclic group Chemical group 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 208000010159 IgA glomerulonephritis Diseases 0.000 claims description 5
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 5
- 125000002619 bicyclic group Chemical group 0.000 claims description 5
- 235000012054 meals Nutrition 0.000 claims description 5
- 201000006417 multiple sclerosis Diseases 0.000 claims description 5
- 201000001320 Atherosclerosis Diseases 0.000 claims description 4
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- 206010018364 Glomerulonephritis Diseases 0.000 claims description 4
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- 206010047115 Vasculitis Diseases 0.000 claims description 4
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- 206010028417 myasthenia gravis Diseases 0.000 claims description 4
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 4
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Classifications
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Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
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- Cardiology (AREA)
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- Transplantation (AREA)
- Pain & Pain Management (AREA)
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- Gastroenterology & Hepatology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
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| EP14003389 | 2014-10-01 | ||
| EP14003389.5 | 2014-10-01 | ||
| PCT/EP2015/001973 WO2016050358A1 (en) | 2014-10-01 | 2015-10-01 | Boronic acid derivatives |
Publications (2)
| Publication Number | Publication Date |
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| KR20170067802A KR20170067802A (ko) | 2017-06-16 |
| KR102457840B1 true KR102457840B1 (ko) | 2022-10-21 |
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| RU2017115191A (ru) | 2014-10-01 | 2018-11-06 | Мерк Патент Гмбх | Производные бороновой кислоты |
| RU2017115193A (ru) | 2014-10-01 | 2018-11-06 | Мерк Патент Гмбх | Производные бороновой кислоты |
| US9453018B2 (en) | 2014-10-01 | 2016-09-27 | Bristol-Myers Squibb Company | Pyrimidinones as factor XIa inhibitors |
| BR112017006420A2 (pt) | 2014-10-01 | 2017-12-19 | Merck Patent Gmbh | derivados de ácido borônico |
| DK3571208T3 (da) | 2017-01-18 | 2021-05-10 | Principia Biopharma Inc | Immunproteasominhibitorer |
| PL3672977T3 (pl) * | 2017-08-24 | 2022-09-26 | Merck Patent Gmbh | Pochodne kwasu boronowego |
| WO2019042301A1 (zh) * | 2017-08-29 | 2019-03-07 | 浙江海正药业股份有限公司 | (E)-α,β-不饱和酰胺化合物及其制备方法和用途 |
| WO2019075386A1 (en) * | 2017-10-13 | 2019-04-18 | The Regents Of The University Of California | MODULATORS OF MTORC1 |
| MA50906A (fr) * | 2017-11-16 | 2020-09-23 | Principia Biopharma Inc | Inhibiteurs d'immunoprotéasome |
| ES2928787T3 (es) * | 2017-11-16 | 2022-11-22 | Principia Biopharma Inc | Inhibidores del inmunoproteasoma |
| SG11202100727VA (en) | 2018-07-26 | 2021-02-25 | Merck Patent Gmbh | Boronic acid derivatives |
| CN113135944A (zh) * | 2020-01-19 | 2021-07-20 | 首药控股(北京)有限公司 | 硼酸衍生物 |
| CN113135943A (zh) * | 2020-01-19 | 2021-07-20 | 首药控股(北京)有限公司 | 硼酸衍生物 |
| WO2023006863A1 (en) | 2021-07-29 | 2023-02-02 | Merck Patent Gmbh | Novel crystalline forms of [(1r)-2-(1-benzofuran-3-yl)-1-{[(1s,2r,4r)-7- oxabicyclo[2.2.1]heptan-2-yl]formamido}ethyl]boronic acid, adducts thereof, and processes to obtain |
| CN118119630A (zh) * | 2021-10-14 | 2024-05-31 | 首药控股(北京)股份有限公司 | 硼酸衍生物 |
| WO2023232830A1 (en) | 2022-06-02 | 2023-12-07 | Merck Patent Gmbh | Boronic acid adducts |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO1996012499A1 (en) * | 1994-10-25 | 1996-05-02 | The Du Pont Merck Pharmaceutical Company | Amidino and guanidino substituted inhibitors of trypsin-like enzymes |
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| IL111175A0 (en) | 1993-10-07 | 1994-12-29 | Du Pont Merck Pharma | Electrophilic peptide analogs as inhibitors of trypsin-like serine proteases and pharmaceutical compositions containing them |
| US5462964A (en) * | 1993-10-20 | 1995-10-31 | The Du Pont Merck Pharmaceutical Company | Dipeptide boronic acid inhibitors of trypsin-like enzymes |
| WO2001002424A2 (en) * | 1999-07-07 | 2001-01-11 | Du Pont Pharmaceuticals Company | Peptide boronic acid inhibitors of hepatitis c virus protease |
| CA2535792A1 (en) * | 2002-09-09 | 2004-03-18 | Trigen Limited | Boronic acid salts ant their use in the treatment of thrombosis |
| UA88771C2 (ru) * | 2003-08-14 | 2009-11-25 | Сефалон, Инк. | Ингибиторы протеасомы и способ их применения (варианты) |
| US7576206B2 (en) * | 2003-08-14 | 2009-08-18 | Cephalon, Inc. | Proteasome inhibitors and methods of using the same |
| AR075090A1 (es) * | 2008-09-29 | 2011-03-09 | Millennium Pharm Inc | Derivados de acido 1-amino-2-ciclobutiletilboronico inhibidores de proteosoma,utiles como agentes anticancerigenos, y composiciones farmaceuticas que los comprenden. |
| CN103068830B (zh) | 2010-04-22 | 2016-06-29 | 马尔斯公司 | 精氨酸酶抑制剂及其治疗应用 |
| SG11201403254QA (en) * | 2011-12-22 | 2014-07-30 | Ares Trading Sa | Alpha-amino boronic acid derivatives, selective immunoproteasome inhibitors |
| CN116987080A (zh) | 2014-01-31 | 2023-11-03 | 百时美施贵宝公司 | 作为因子xia抑制剂的具有杂环p2′基团的大环化合物 |
| RU2017115191A (ru) | 2014-10-01 | 2018-11-06 | Мерк Патент Гмбх | Производные бороновой кислоты |
| ME03344B (me) | 2014-10-01 | 2019-10-20 | Janssen Pharmaceuticals Inc | Mono- ili di-supstituisani indoli kao inнibitori replikacije denga virusa |
| NO2721243T3 (https=) | 2014-10-01 | 2018-10-20 | ||
| AU2015326930B2 (en) | 2014-10-01 | 2020-03-26 | Janssen Pharmaceuticals, Inc. | Mono- or di-substituted indole derivatives as dengue viral replication inhibitors |
| BR112017006420A2 (pt) | 2014-10-01 | 2017-12-19 | Merck Patent Gmbh | derivados de ácido borônico |
| RU2017115193A (ru) | 2014-10-01 | 2018-11-06 | Мерк Патент Гмбх | Производные бороновой кислоты |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996012499A1 (en) * | 1994-10-25 | 1996-05-02 | The Du Pont Merck Pharmaceutical Company | Amidino and guanidino substituted inhibitors of trypsin-like enzymes |
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| WO2016050358A1 (en) | 2016-04-07 |
| EP3201206B1 (en) | 2019-09-18 |
| DK3201206T3 (da) | 2019-12-16 |
| IL251302A0 (en) | 2017-05-29 |
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| CN107001391B (zh) | 2020-11-27 |
| KR20170067802A (ko) | 2017-06-16 |
| RU2717558C2 (ru) | 2020-03-24 |
| BR112017006622A2 (pt) | 2018-07-03 |
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| AU2015327345B9 (en) | 2020-06-18 |
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| MY186911A (en) | 2021-08-26 |
| UA122672C2 (uk) | 2020-12-28 |
| JP6662865B2 (ja) | 2020-03-11 |
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| CN107001391A (zh) | 2017-08-01 |
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| PH12017500293A1 (en) | 2017-06-28 |
| CA2963203A1 (en) | 2016-04-07 |
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| KR102457840B1 (ko) | 보론산 유도체 | |
| US10640520B2 (en) | Boronic acid derivatives | |
| KR102450583B1 (ko) | 보론산 유도체 | |
| US10253049B2 (en) | Boronic acid derivatives |
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