KR20100120709A - Ｐｉｍ 키나제 억제제 및 이들의 사용 방법 - Google Patents
Ｐｉｍ 키나제 억제제 및 이들의 사용 방법 Download PDFInfo
- Publication number
- KR20100120709A KR20100120709A KR1020107022008A KR20107022008A KR20100120709A KR 20100120709 A KR20100120709 A KR 20100120709A KR 1020107022008 A KR1020107022008 A KR 1020107022008A KR 20107022008 A KR20107022008 A KR 20107022008A KR 20100120709 A KR20100120709 A KR 20100120709A
- Authority
- KR
- South Korea
- Prior art keywords
- tert
- amino
- equiv
- thiazole
- pyridin
- 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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- 238000000034 method Methods 0.000 title claims description 76
- 229940043355 kinase inhibitor Drugs 0.000 title 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 120
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- 206010028980 Neoplasm Diseases 0.000 claims abstract description 22
- 230000000694 effects Effects 0.000 claims abstract description 22
- 201000011510 cancer Diseases 0.000 claims abstract description 20
- 239000003814 drug Substances 0.000 claims abstract description 17
- 238000011282 treatment Methods 0.000 claims abstract description 13
- 108091000080 Phosphotransferase Proteins 0.000 claims abstract description 12
- 102000020233 phosphotransferase Human genes 0.000 claims abstract description 12
- 239000003937 drug carrier Substances 0.000 claims abstract description 7
- 229940124597 therapeutic agent Drugs 0.000 claims abstract description 6
- -1 amino, methyl Chemical group 0.000 claims description 224
- 239000000203 mixture Substances 0.000 claims description 76
- 229910052739 hydrogen Inorganic materials 0.000 claims description 40
- 125000000217 alkyl group Chemical group 0.000 claims description 31
- 229910052731 fluorine Inorganic materials 0.000 claims description 26
- 125000003118 aryl group Chemical group 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 229910052801 chlorine Inorganic materials 0.000 claims description 15
- 101000595531 Homo sapiens Serine/threonine-protein kinase pim-1 Proteins 0.000 claims description 14
- 102100036077 Serine/threonine-protein kinase pim-1 Human genes 0.000 claims description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 150000001408 amides Chemical class 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 7
- 125000001188 haloalkyl group Chemical group 0.000 claims description 7
- 125000001072 heteroaryl group Chemical group 0.000 claims description 7
- 230000002401 inhibitory effect Effects 0.000 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- PQQRHWFRZHFGFM-UHFFFAOYSA-N 1,3-thiazole-4-carboxamide Chemical compound NC(=O)C1=CSC=N1 PQQRHWFRZHFGFM-UHFFFAOYSA-N 0.000 claims description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 6
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 6
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- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 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 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 125000003386 piperidinyl group Chemical group 0.000 claims description 3
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 7
- BXDZOYLPNAIDOC-UHFFFAOYSA-N N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-1-[2-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]ethylamino]-2-oxoethyl]piperidine-4-carboxamide Chemical compound CC(C)(C)c1cnc(CSc2cnc(NC(=O)C3CCN(CC(=O)NCCOCCOCCOCCNc4cccc5C(=O)N(C6CCC(=O)NC6=O)C(=O)c45)CC3)s2)o1 BXDZOYLPNAIDOC-UHFFFAOYSA-N 0.000 claims 2
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 74
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
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- 229920006395 saturated elastomer Polymers 0.000 description 59
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 56
- 239000012267 brine Substances 0.000 description 51
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 51
- 239000011541 reaction mixture Substances 0.000 description 50
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 47
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- 238000003756 stirring Methods 0.000 description 40
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 38
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- JOTRPRKONYTVBV-UHFFFAOYSA-N 4-chloro-3-nitropyridine Chemical compound [O-][N+](=O)C1=CN=CC=C1Cl JOTRPRKONYTVBV-UHFFFAOYSA-N 0.000 description 28
- 210000004027 cell Anatomy 0.000 description 28
- 238000004128 high performance liquid chromatography Methods 0.000 description 28
- 230000002829 reductive effect Effects 0.000 description 28
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 26
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- 239000000047 product Substances 0.000 description 26
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 25
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- 239000012298 atmosphere Substances 0.000 description 24
- 239000001257 hydrogen Substances 0.000 description 24
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 22
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 21
- 239000011780 sodium chloride Substances 0.000 description 21
- 125000006633 tert-butoxycarbonylamino group Chemical group 0.000 description 20
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 19
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
- 239000000706 filtrate Substances 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- 229940086542 triethylamine Drugs 0.000 description 18
- QLILRKBRWXALIE-UHFFFAOYSA-N 3-nitropyridine Chemical compound [O-][N+](=O)C1=CC=CN=C1 QLILRKBRWXALIE-UHFFFAOYSA-N 0.000 description 17
- 239000012044 organic layer Substances 0.000 description 16
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 16
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 13
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- 101150056413 Pim1 gene Proteins 0.000 description 11
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 11
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
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- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- GFFXZLZWLOBBLO-ASKVSEFXSA-N tezacitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(=C/F)/[C@H](O)[C@@H](CO)O1 GFFXZLZWLOBBLO-ASKVSEFXSA-N 0.000 description 1
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- 238000002560 therapeutic procedure Methods 0.000 description 1
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- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 150000003567 thiocyanates Chemical class 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 208000013077 thyroid gland carcinoma Diseases 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
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- 230000001988 toxicity Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
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- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
- 229960000575 trastuzumab Drugs 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- IMNIECVIVJOTBH-UHFFFAOYSA-N trifluoromethanesulfonyl bromide Chemical group FC(F)(F)S(Br)(=O)=O IMNIECVIVJOTBH-UHFFFAOYSA-N 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical class CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Virology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3335908P | 2008-03-03 | 2008-03-03 | |
| US61/033,359 | 2008-03-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20100120709A true KR20100120709A (ko) | 2010-11-16 |
Family
ID=41055566
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020107022008A Withdrawn KR20100120709A (ko) | 2008-03-03 | 2009-03-03 | Ｐｉｍ 키나제 억제제 및 이들의 사용 방법 |
Country Status (21)
| Country | Link |
|---|---|
| EP (2) | EP2596790B1 (https=) |
| JP (1) | JP5412448B2 (https=) |
| KR (1) | KR20100120709A (https=) |
| CN (2) | CN104098559A (https=) |
| AR (1) | AR070531A1 (https=) |
| AU (1) | AU2009221134B2 (https=) |
| BR (1) | BRPI0909102A2 (https=) |
| CA (1) | CA2717388A1 (https=) |
| CL (1) | CL2009000483A1 (https=) |
| CO (1) | CO6290687A2 (https=) |
| EA (1) | EA201001412A1 (https=) |
| EC (1) | ECSP10010447A (https=) |
| ES (2) | ES2443496T3 (https=) |
| IL (1) | IL207865A0 (https=) |
| MA (1) | MA32135B1 (https=) |
| MX (1) | MX2010009739A (https=) |
| PE (1) | PE20091577A1 (https=) |
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| UY (1) | UY31679A1 (https=) |
| WO (1) | WO2009109576A1 (https=) |
| ZA (1) | ZA201006128B (https=) |
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| US9156827B2 (en) | 2010-04-30 | 2015-10-13 | The University Of Tokyo | Anticancer agent |
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| AR113922A1 (es) | 2017-12-08 | 2020-07-01 | Incyte Corp | Terapia de combinación de dosis baja para el tratamiento de neoplasias mieloproliferativas |
| WO2019111218A1 (en) | 2017-12-08 | 2019-06-13 | Cadila Healthcare Limited | Novel heterocyclic compounds as irak4 inhibitors |
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| MX2009009304A (es) * | 2007-03-01 | 2009-11-18 | Novartis Ag | Inhibidores de cinasa pim y metodos para su uso. |
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2009
- 2009-02-27 AR ARP090100684A patent/AR070531A1/es not_active Application Discontinuation
- 2009-02-27 UY UY031679A patent/UY31679A1/es not_active Application Discontinuation
- 2009-02-27 PE PE2009000308A patent/PE20091577A1/es not_active Application Discontinuation
- 2009-03-02 TW TW098106739A patent/TW200942536A/zh unknown
- 2009-03-02 CL CL2009000483A patent/CL2009000483A1/es unknown
- 2009-03-03 EP EP13154157.5A patent/EP2596790B1/en active Active
- 2009-03-03 CN CN201410286911.5A patent/CN104098559A/zh active Pending
- 2009-03-03 MX MX2010009739A patent/MX2010009739A/es not_active Application Discontinuation
- 2009-03-03 AU AU2009221134A patent/AU2009221134B2/en not_active Expired - Fee Related
- 2009-03-03 CN CN200980115821.7A patent/CN102015701B/zh active Active
- 2009-03-03 ES ES09717066.6T patent/ES2443496T3/es active Active
- 2009-03-03 KR KR1020107022008A patent/KR20100120709A/ko not_active Withdrawn
- 2009-03-03 JP JP2010549127A patent/JP5412448B2/ja active Active
- 2009-03-03 BR BRPI0909102A patent/BRPI0909102A2/pt not_active IP Right Cessation
- 2009-03-03 ES ES13154157.5T patent/ES2562306T3/es active Active
- 2009-03-03 CA CA2717388A patent/CA2717388A1/en not_active Abandoned
- 2009-03-03 EA EA201001412A patent/EA201001412A1/ru unknown
- 2009-03-03 EP EP09717066.6A patent/EP2262802B1/en active Active
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2010
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- 2010-09-02 MA MA33140A patent/MA32135B1/fr unknown
- 2010-09-03 EC EC2010010447A patent/ECSP10010447A/es unknown
- 2010-09-07 CO CO10110544A patent/CO6290687A2/es not_active Application Discontinuation
Also Published As
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| AU2009221134B2 (en) | 2012-02-23 |
| CN102015701A (zh) | 2011-04-13 |
| AU2009221134A1 (en) | 2009-09-11 |
| ES2443496T3 (es) | 2014-02-19 |
| BRPI0909102A2 (pt) | 2019-01-15 |
| JP5412448B2 (ja) | 2014-02-12 |
| CO6290687A2 (es) | 2011-06-20 |
| ZA201006128B (en) | 2011-10-26 |
| WO2009109576A1 (en) | 2009-09-11 |
| ES2562306T3 (es) | 2016-03-03 |
| EP2596790A1 (en) | 2013-05-29 |
| UY31679A1 (es) | 2009-09-30 |
| TW200942536A (en) | 2009-10-16 |
| CL2009000483A1 (es) | 2010-02-19 |
| MX2010009739A (es) | 2010-09-28 |
| EP2596790B1 (en) | 2015-12-09 |
| AR070531A1 (es) | 2010-04-14 |
| ECSP10010447A (es) | 2010-10-30 |
| MA32135B1 (fr) | 2011-03-01 |
| CN104098559A (zh) | 2014-10-15 |
| EP2262802A1 (en) | 2010-12-22 |
| EP2262802B1 (en) | 2013-10-23 |
| CA2717388A1 (en) | 2009-09-11 |
| EA201001412A1 (ru) | 2011-06-30 |
| CN102015701B (zh) | 2014-07-23 |
| IL207865A0 (en) | 2010-12-30 |
| JP2011513363A (ja) | 2011-04-28 |
| PE20091577A1 (es) | 2009-11-05 |
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