JP2011518816A - Ｐｌｋインヒビター - Google Patents
Ｐｌｋインヒビター Download PDFInfo
- Publication number
- JP2011518816A JP2011518816A JP2011505583A JP2011505583A JP2011518816A JP 2011518816 A JP2011518816 A JP 2011518816A JP 2011505583 A JP2011505583 A JP 2011505583A JP 2011505583 A JP2011505583 A JP 2011505583A JP 2011518816 A JP2011518816 A JP 2011518816A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- hydrogen
- optionally substituted
- group
- alkenyl
- 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- Withdrawn
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- 239000003112 inhibitor Substances 0.000 title abstract description 13
- 150000001875 compounds Chemical class 0.000 claims abstract description 78
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 68
- 239000001257 hydrogen Substances 0.000 claims abstract description 68
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 63
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 53
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 27
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 27
- 125000002950 monocyclic group Chemical group 0.000 claims abstract description 23
- 125000006413 ring segment Chemical group 0.000 claims abstract description 23
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 20
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 13
- 201000010099 disease Diseases 0.000 claims abstract description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 12
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 10
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 9
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 8
- 150000002367 halogens Chemical class 0.000 claims abstract description 8
- 125000002619 bicyclic group Chemical group 0.000 claims abstract description 7
- 230000002062 proliferating effect Effects 0.000 claims abstract description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract 3
- -1 methylpiperidin-4-yl Chemical group 0.000 claims description 43
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
- 102100031463 Serine/threonine-protein kinase PLK1 Human genes 0.000 claims description 19
- 108010056274 polo-like kinase 1 Proteins 0.000 claims description 19
- 125000001424 substituent group Chemical group 0.000 claims description 19
- 238000000034 method Methods 0.000 claims description 18
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 16
- 230000000694 effects Effects 0.000 claims description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 13
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 13
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- 102000013392 Carboxylesterase Human genes 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 11
- 125000001072 heteroaryl group Chemical group 0.000 claims description 11
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
- 125000004076 pyridyl group Chemical group 0.000 claims description 11
- 230000003834 intracellular effect Effects 0.000 claims description 10
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 10
- 150000001721 carbon Chemical group 0.000 claims description 8
- 125000004185 ester group Chemical group 0.000 claims description 8
- 125000002527 bicyclic carbocyclic group Chemical group 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 6
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- 150000003568 thioethers Chemical class 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 201000011510 cancer Diseases 0.000 claims description 5
- 125000002843 carboxylic acid group Chemical group 0.000 claims description 5
- 125000000524 functional group Chemical group 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000006554 (C4-C8) cycloalkenyl group Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 3
- 125000006590 (C2-C6) alkenylene group Chemical group 0.000 claims description 3
- 125000006591 (C2-C6) alkynylene group Chemical group 0.000 claims description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 2
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 2
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 2
- 238000001727 in vivo Methods 0.000 claims description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 2
- 230000001404 mediated effect Effects 0.000 claims description 2
- 125000001620 monocyclic carbocycle group Chemical group 0.000 claims description 2
- 125000006203 morpholinoethyl group Chemical group [H]C([H])(*)C([H])([H])N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 2
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 2
- DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 claims 1
- 125000003275 alpha amino acid group Chemical group 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- 150000001413 amino acids Chemical class 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- 210000004027 cell Anatomy 0.000 description 25
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 150000002148 esters Chemical class 0.000 description 16
- 239000000047 product Substances 0.000 description 16
- 230000002829 reductive effect Effects 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- 239000000543 intermediate Substances 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 238000005481 NMR spectroscopy Methods 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 11
- 239000011541 reaction mixture Substances 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 238000003556 assay Methods 0.000 description 9
- 125000004432 carbon atom Chemical group C* 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 235000019439 ethyl acetate Nutrition 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 8
- 238000002866 fluorescence resonance energy transfer Methods 0.000 description 8
- 108090000765 processed proteins & peptides Proteins 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
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- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 7
- 235000001014 amino acid Nutrition 0.000 description 7
- 229940024606 amino acid Drugs 0.000 description 7
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- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
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- 229920006395 saturated elastomer Polymers 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
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- GCHPUFAZSONQIV-YFKPBYRVSA-N (2s)-2-azaniumyl-2-methylbutanoate Chemical compound CC[C@](C)([NH3+])C([O-])=O GCHPUFAZSONQIV-YFKPBYRVSA-N 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- 150000001204 N-oxides Chemical class 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
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- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
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- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D475/00—Heterocyclic compounds containing pteridine ring systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Pharmacology & Pharmacy (AREA)
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- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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| GB0807451.0 | 2008-04-24 | ||
| PCT/GB2009/001019 WO2009130453A1 (en) | 2008-04-24 | 2009-04-23 | Inhibitors of plk |
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| JP2011518816A true JP2011518816A (ja) | 2011-06-30 |
| JP2011518816A5 JP2011518816A5 (enExample) | 2012-05-31 |
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| JP (1) | JP2011518816A (enExample) |
| GB (1) | GB0807451D0 (enExample) |
| WO (1) | WO2009130453A1 (enExample) |
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| GB0803747D0 (en) * | 2008-02-29 | 2008-04-09 | Martin | Enzyme and receptor modulation |
| GB0903480D0 (en) | 2009-02-27 | 2009-04-08 | Chroma Therapeutics Ltd | Enzyme Inhibitors |
| CN102762568A (zh) * | 2009-12-23 | 2012-10-31 | 伊兰药品公司 | 作为polo样激酶的抑制剂的蝶啶酮 |
| GB201211310D0 (en) | 2012-06-26 | 2012-08-08 | Chroma Therapeutics Ltd | CSF-1R kinase inhibitors |
| SI3222616T1 (sl) | 2012-10-17 | 2019-10-30 | Macrophage Pharma Ltd | N-(2-(4-(6-amino-5-(2,4-difluorobenzoil)-2-oksopiridin-1(2H)-IL)-3,5- difluorofenil)etil)-L-alanin in njegov terbutil ester |
| JP6815318B2 (ja) * | 2014-12-23 | 2021-01-20 | ダナ−ファーバー キャンサー インスティテュート，インコーポレイテッド | 二官能性分子によって標的化タンパク質分解を誘導する方法 |
| GB201713975D0 (en) | 2017-08-31 | 2017-10-18 | Macrophage Pharma Ltd | Medical use |
| KR20260019479A (ko) | 2023-05-04 | 2026-02-10 | 레볼루션 메디슨즈, 인크. | Ras 관련 질환 또는 장애를 위한 병용 요법 |
| CN121889155A (zh) | 2023-08-07 | 2026-04-17 | 锐新医药公司 | 用于治疗ras蛋白相关疾病或病症的rmc-6291 |
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| WO2026112260A1 (en) | 2024-11-21 | 2026-05-28 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2026122764A2 (en) | 2024-12-06 | 2026-06-11 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2026128688A2 (en) | 2024-12-13 | 2026-06-18 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2026161839A1 (en) | 2025-01-27 | 2026-07-30 | Revolution Medicines, Inc. | Ras inhibitors |
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|---|---|---|---|---|
| WO2006021548A1 (de) * | 2004-08-27 | 2006-03-02 | Boehringer Ingelheim International Gmbh | Dihydropteridinone, verfahren zu deren herstellung und deren verwendung als arzneimittel |
| BRPI0718120A2 (pt) * | 2006-10-25 | 2013-11-12 | Chroma Therapeutics Ltd | Derivados de pteridina como inibidores de cinase do tipo pólo úteis no tratamento de câncer |
-
2008
- 2008-04-24 GB GBGB0807451.0A patent/GB0807451D0/en not_active Ceased
-
2009
- 2009-04-23 EP EP09735114A patent/EP2296662A1/en not_active Withdrawn
- 2009-04-23 JP JP2011505583A patent/JP2011518816A/ja not_active Withdrawn
- 2009-04-23 US US12/989,178 patent/US20110190306A1/en not_active Abandoned
- 2009-04-23 WO PCT/GB2009/001019 patent/WO2009130453A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| GB0807451D0 (en) | 2008-05-28 |
| WO2009130453A1 (en) | 2009-10-29 |
| EP2296662A1 (en) | 2011-03-23 |
| US20110190306A1 (en) | 2011-08-04 |
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