AU2008228303B2 - Substituted pyrimidodiazepines useful as PLK1 inhibitors - Google Patents
Substituted pyrimidodiazepines useful as PLK1 inhibitors Download PDFInfo
- Publication number
- AU2008228303B2 AU2008228303B2 AU2008228303A AU2008228303A AU2008228303B2 AU 2008228303 B2 AU2008228303 B2 AU 2008228303B2 AU 2008228303 A AU2008228303 A AU 2008228303A AU 2008228303 A AU2008228303 A AU 2008228303A AU 2008228303 B2 AU2008228303 B2 AU 2008228303B2
- Authority
- AU
- Australia
- Prior art keywords
- methyl
- mole
- tetrahydro
- pyrimido
- diazepin
- 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.)
- Ceased
Links
- 102100031463 Serine/threonine-protein kinase PLK1 Human genes 0.000 title abstract description 14
- 108010056274 polo-like kinase 1 Proteins 0.000 title abstract description 13
- 239000003112 inhibitor Substances 0.000 title abstract description 5
- OHXQYFCNXHGKPJ-UHFFFAOYSA-N 1h-pyrimido[5,4-c]diazepine Chemical class N1N=CC=CC2=NC=NC=C12 OHXQYFCNXHGKPJ-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 51
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 15
- DQJHTCZROXSXEZ-UHFFFAOYSA-N 4-[(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-8h-pyrimido[4,5-b][1,4]diazepin-2-yl)amino]-3-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1NC1=NC=C(N(C)C(=O)C(F)(F)CN2C3CCCC3)C2=N1 DQJHTCZROXSXEZ-UHFFFAOYSA-N 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 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 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 239000000203 mixture Substances 0.000 abstract description 397
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 7
- 206010028980 Neoplasm Diseases 0.000 abstract description 6
- 230000000771 oncological effect Effects 0.000 abstract description 4
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 abstract description 3
- 210000000481 breast Anatomy 0.000 abstract description 3
- 210000001072 colon Anatomy 0.000 abstract description 3
- 201000010099 disease Diseases 0.000 abstract description 3
- 210000004072 lung Anatomy 0.000 abstract description 3
- 230000002062 proliferating effect Effects 0.000 abstract description 3
- 208000026310 Breast neoplasm Diseases 0.000 abstract description 2
- 208000029742 colonic neoplasm Diseases 0.000 abstract description 2
- 238000009472 formulation Methods 0.000 abstract description 2
- 208000037841 lung tumor Diseases 0.000 abstract description 2
- 208000023958 prostate neoplasm Diseases 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 531
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 299
- 230000002829 reductive effect Effects 0.000 description 217
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 193
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 153
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 147
- 239000000243 solution Substances 0.000 description 146
- 239000007787 solid Substances 0.000 description 117
- -1 PLK1 Proteins 0.000 description 112
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 94
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 94
- 239000012267 brine Substances 0.000 description 82
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 82
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 81
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 78
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 74
- 238000000746 purification Methods 0.000 description 58
- 238000000034 method Methods 0.000 description 54
- 238000001914 filtration Methods 0.000 description 51
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 48
- 239000012044 organic layer Substances 0.000 description 43
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 41
- 239000002244 precipitate Substances 0.000 description 40
- KYSGSGFXDCAVQB-UHFFFAOYSA-N 2-chloro-9-cyclopentyl-5,7-dimethyl-7,8-dihydropyrimido[4,5-b][1,4]diazepin-6-one Chemical compound C12=NC(Cl)=NC=C2N(C)C(=O)C(C)CN1C1CCCC1 KYSGSGFXDCAVQB-UHFFFAOYSA-N 0.000 description 39
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- 239000001257 hydrogen Substances 0.000 description 38
- 229910052739 hydrogen Inorganic materials 0.000 description 38
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 37
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 35
- 239000012071 phase Substances 0.000 description 35
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 33
- ALOCUZOKRULSAA-UHFFFAOYSA-N 1-methylpiperidin-4-amine Chemical compound CN1CCC(N)CC1 ALOCUZOKRULSAA-UHFFFAOYSA-N 0.000 description 32
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- 239000003921 oil Substances 0.000 description 31
- 235000019198 oils Nutrition 0.000 description 31
- INUSQTPGSHFGHM-UHFFFAOYSA-N 2,4-dichloro-5-nitropyrimidine Chemical compound [O-][N+](=O)C1=CN=C(Cl)N=C1Cl INUSQTPGSHFGHM-UHFFFAOYSA-N 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- 238000001816 cooling Methods 0.000 description 28
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 27
- 235000015497 potassium bicarbonate Nutrition 0.000 description 27
- 239000011736 potassium bicarbonate Substances 0.000 description 27
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 27
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 26
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- 238000010992 reflux Methods 0.000 description 26
- 239000000284 extract Substances 0.000 description 25
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 23
- 239000012312 sodium hydride Substances 0.000 description 23
- 229910000104 sodium hydride Inorganic materials 0.000 description 23
- JNFGLYJROFAOQP-UHFFFAOYSA-N 4-amino-3-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1N JNFGLYJROFAOQP-UHFFFAOYSA-N 0.000 description 22
- 239000000706 filtrate Substances 0.000 description 22
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 22
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- GJJNFZOPTJVXID-UHFFFAOYSA-N 5,7,8,9-tetrahydropyrimido[4,5-b][1,4]diazepin-6-one Chemical compound N1C(=O)CCNC2=NC=NC=C21 GJJNFZOPTJVXID-UHFFFAOYSA-N 0.000 description 20
- 239000000843 powder Substances 0.000 description 20
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 20
- 235000017557 sodium bicarbonate Nutrition 0.000 description 20
- 239000008346 aqueous phase Substances 0.000 description 19
- 239000012074 organic phase Substances 0.000 description 19
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Chemical compound O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 18
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- 239000003054 catalyst Substances 0.000 description 16
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- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 14
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 14
- 239000000725 suspension Substances 0.000 description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
- PDKXJKWLFFZPPF-UHFFFAOYSA-N [dimethylamino-(3-oxidotriazolo[4,5-b]pyridin-3-ium-1-yl)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(C(N(C)C)=[N+](C)C)N=[N+]([O-])C2=N1 PDKXJKWLFFZPPF-UHFFFAOYSA-N 0.000 description 13
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- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 12
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 11
- 229910000024 caesium carbonate Inorganic materials 0.000 description 11
- 238000004587 chromatography analysis Methods 0.000 description 11
- 150000002431 hydrogen Chemical class 0.000 description 11
- 229960004592 isopropanol Drugs 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
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- 238000003756 stirring Methods 0.000 description 11
- 239000005711 Benzoic acid Substances 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- 235000011114 ammonium hydroxide Nutrition 0.000 description 10
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 10
- VSMSBPFQRFQLGA-UHFFFAOYSA-N 4-[(9-cyclohexyl-6-oxo-7,8-dihydro-5h-pyrimido[4,5-b][1,4]diazepin-2-yl)amino]-2-methoxybenzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC(NC=2N=C3N(C4CCCCC4)CCC(=O)NC3=CN=2)=C1 VSMSBPFQRFQLGA-UHFFFAOYSA-N 0.000 description 9
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- XQSNXLDLKOJJOU-UHFFFAOYSA-N pyrimido[5,4-c]diazepin-3-one Chemical compound N1=NC(=O)C=CC2=NC=NC=C21 XQSNXLDLKOJJOU-UHFFFAOYSA-N 0.000 description 9
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- 125000000217 alkyl group Chemical group 0.000 description 8
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- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 8
- 125000004494 ethyl ester group Chemical group 0.000 description 8
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 7
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- 125000003118 aryl group Chemical group 0.000 description 7
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- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 7
- SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical class ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 7
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- JXYPNRIYAMXJSE-UHFFFAOYSA-N 1,4-diazepin-6-one Chemical compound O=C1C=NC=CN=C1 JXYPNRIYAMXJSE-UHFFFAOYSA-N 0.000 description 6
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- 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 description 5
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- LIMGJPPDWITRHN-UHFFFAOYSA-N 2-chloro-9-cyclopentyl-7-methyl-7,8-dihydro-5h-pyrimido[4,5-b][1,4]diazepin-6-one Chemical compound C12=NC(Cl)=NC=C2NC(=O)C(C)CN1C1CCCC1 LIMGJPPDWITRHN-UHFFFAOYSA-N 0.000 description 4
- XHQZJYCNDZAGLW-UHFFFAOYSA-N 3-methoxybenzoic acid Chemical compound COC1=CC=CC(C(O)=O)=C1 XHQZJYCNDZAGLW-UHFFFAOYSA-N 0.000 description 4
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- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
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- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
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- 230000003595 spectral effect Effects 0.000 description 1
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- 239000001119 stannous chloride Substances 0.000 description 1
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- 235000003702 sterols Nutrition 0.000 description 1
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- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 238000004808 supercritical fluid chromatography Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- QWKSWHYKNGQDPQ-UHFFFAOYSA-N tert-butyl 3-(2-methoxyethylamino)propanoate Chemical compound COCCNCCC(=O)OC(C)(C)C QWKSWHYKNGQDPQ-UHFFFAOYSA-N 0.000 description 1
- NIYLFPXKKQMEIR-UHFFFAOYSA-N tert-butyl 3-(butylamino)propanoate Chemical compound CCCCNCCC(=O)OC(C)(C)C NIYLFPXKKQMEIR-UHFFFAOYSA-N 0.000 description 1
- IZQPJSKNBSULAJ-UHFFFAOYSA-N tert-butyl 3-(propan-2-ylamino)propanoate Chemical compound CC(C)NCCC(=O)OC(C)(C)C IZQPJSKNBSULAJ-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
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- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
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- 230000007704 transition Effects 0.000 description 1
- 229960001124 trientine Drugs 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
- UJMBCXLDXJUMFB-UHFFFAOYSA-K trisodium;5-oxo-1-(4-sulfonatophenyl)-4-[(4-sulfonatophenyl)diazenyl]-4h-pyrazole-3-carboxylate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)C1=NN(C=2C=CC(=CC=2)S([O-])(=O)=O)C(=O)C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 UJMBCXLDXJUMFB-UHFFFAOYSA-K 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 125000005023 xylyl group Chemical group 0.000 description 1
- 238000011911 α-alkylation Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
-
- 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
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/18—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/18—Bridged systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US91935807P | 2007-03-22 | 2007-03-22 | |
| US60/919,358 | 2007-03-22 | ||
| PCT/EP2008/052847 WO2008113711A1 (en) | 2007-03-22 | 2008-03-11 | Substituted pyrimidodiazepines useful as plk1 inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2008228303A1 AU2008228303A1 (en) | 2008-09-25 |
| AU2008228303B2 true AU2008228303B2 (en) | 2012-04-19 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| AU2008228303A Ceased AU2008228303B2 (en) | 2007-03-22 | 2008-03-11 | Substituted pyrimidodiazepines useful as PLK1 inhibitors |
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| Country | Link |
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| EP (1) | EP2139892B1 (enExample) |
| JP (1) | JP5087640B2 (enExample) |
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| AT (1) | ATE524472T1 (enExample) |
| AU (1) | AU2008228303B2 (enExample) |
| BR (1) | BRPI0809088A2 (enExample) |
| CA (1) | CA2680757A1 (enExample) |
| CL (1) | CL2008000785A1 (enExample) |
| CY (1) | CY1112102T1 (enExample) |
| DK (1) | DK2139892T3 (enExample) |
| ES (1) | ES2371832T3 (enExample) |
| HR (1) | HRP20110807T1 (enExample) |
| IL (1) | IL200617A (enExample) |
| MX (1) | MX2009010034A (enExample) |
| PE (1) | PE20120495A1 (enExample) |
| PL (1) | PL2139892T3 (enExample) |
| PT (1) | PT2139892E (enExample) |
| SI (1) | SI2139892T1 (enExample) |
| TW (1) | TWI363629B (enExample) |
| WO (1) | WO2008113711A1 (enExample) |
Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2190849B1 (en) * | 2007-08-15 | 2013-11-20 | Vertex Pharmceuticals Incorporated | 4-(9-(3,3-difluorocyclopentyl)-5,7,7-trimethyl-6-oxo-6,7,8,9-tetrahydro-5h-pyrimido[4,5-b[1,4]diazepin-2-ylamino)-3-methoxybenzamide derivatives as inhibitors of the human protein kinases plk1 to plk4 for the treatment of proliferative diseases |
| NZ584760A (en) * | 2007-09-25 | 2012-03-30 | Takeda Pharmaceutical | Polo-like kinase inhibitors |
| EP2610256B1 (en) * | 2007-09-28 | 2016-04-27 | Cyclacel Limited | Pyrimidine derivatives as protein kinase inhibitors |
| US20090291938A1 (en) * | 2007-11-19 | 2009-11-26 | Takeda Pharmaceutical Company Limited | Polo-like kinase inhibitors |
| TWI490214B (zh) | 2008-05-30 | 2015-07-01 | 艾德克 上野股份有限公司 | 苯或噻吩衍生物及該等作為ｖａｐ－１抑制劑之用途 |
| EP2303889A1 (en) | 2008-06-18 | 2011-04-06 | F. Hoffmann-La Roche AG | Halo-substituted pyrimidodiazepines as plkl inhibitors |
| EA026557B1 (ru) * | 2008-12-09 | 2017-04-28 | Джилид Сайэнс, Инк. | Промежуточные соединения для получения модуляторов толл-подобных рецепторов |
| EP2379559B1 (en) | 2009-01-06 | 2017-10-25 | Dana-Farber Cancer Institute, Inc. | Pyrimido-diazepinone kinase scaffold compounds and methods of treating disorders |
| GEP20207129B (en) | 2009-06-17 | 2020-07-10 | Vertex Pharma | Inhibitors of influenza viruses replication |
| CA2772253C (en) | 2009-09-14 | 2018-02-27 | Gilead Sciences, Inc. | Modulators of toll-like receptors |
| CN103492381A (zh) | 2010-12-16 | 2014-01-01 | 沃泰克斯药物股份有限公司 | 流感病毒复制的抑制剂 |
| UA118010C2 (uk) | 2011-08-01 | 2018-11-12 | Вертекс Фармасьютікалз Інкорпорейтед | Інгібітори реплікації вірусів грипу |
| JP6553589B2 (ja) | 2013-03-15 | 2019-07-31 | 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 | ピリミド−ジアゼピノン化合物および障害の治療方法 |
| CA2918910A1 (en) | 2013-07-25 | 2015-01-29 | Dana-Farber Cancer Institute, Inc. | Inhibitors of transcription factors and uses thereof |
| TWI652014B (zh) | 2013-09-13 | 2019-03-01 | 美商艾佛艾姆希公司 | 雜環取代之雙環唑殺蟲劑 |
| EP3421468B1 (en) | 2013-11-13 | 2020-11-04 | Vertex Pharmaceuticals Incorporated | Methods of preparing inhibitors of influenza viruses replication |
| HRP20191525T1 (hr) | 2013-11-13 | 2019-11-29 | Vertex Pharma | Inhibitori replikacije virusa influence |
| KR20160115953A (ko) | 2014-01-31 | 2016-10-06 | 다나-파버 캔서 인스티튜트 인크. | 디아미노피리미딘 벤젠술폰 유도체 및 그의 용도 |
| JP2017504651A (ja) | 2014-01-31 | 2017-02-09 | 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 | ジアゼパン誘導体の使用 |
| PT3166607T (pt) | 2014-07-11 | 2022-12-07 | Gilead Sciences Inc | Moduladores de receptores de tipo toll para o tratamento do vih |
| JP2017526741A (ja) | 2014-08-08 | 2017-09-14 | 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 | ジアゼパン誘導体およびその使用 |
| CN107074860B (zh) | 2014-09-16 | 2022-07-15 | 吉利德科学公司 | 制备toll样受体调节剂的方法 |
| AU2015318061B2 (en) | 2014-09-16 | 2018-05-17 | Gilead Sciences, Inc. | Solid forms of a toll-like receptor modulator |
| WO2016183120A1 (en) | 2015-05-13 | 2016-11-17 | Vertex Pharmaceuticals Incorporated | Inhibitors of influenza viruses replication |
| JP6704416B2 (ja) | 2015-05-13 | 2020-06-03 | バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ | インフルエンザウイルスの複製の阻害剤を調製する方法 |
| WO2016201370A1 (en) | 2015-06-12 | 2016-12-15 | Dana-Farber Cancer Institute, Inc. | Combination therapy of transcription inhibitors and kinase inhibitors |
| HK1256419A1 (zh) | 2015-09-11 | 2019-09-20 | 达纳-法伯癌症研究所股份有限公司 | 乙酰胺噻吩並三唑並二氮雜環庚三烯及其用途 |
| PE20181287A1 (es) | 2015-09-11 | 2018-08-07 | Dana Farber Cancer Inst Inc | Ciano tienotriazolpirazinas y usos de las mismas |
| SG10201913450PA (en) | 2015-11-25 | 2020-03-30 | Dana Farber Cancer Inst Inc | Bivalent bromodomain inhibitors and uses thereof |
| AU2017248186B2 (en) * | 2016-04-07 | 2021-10-21 | Dana-Farber Cancer Institute, Inc. | Pyrimido-diazepinone kinase scaffold compounds and methods of treating PI3K-mediated disorders |
| EP4034132A4 (en) * | 2019-09-27 | 2023-10-11 | Dana-Farber Cancer Institute, Inc. | Erk5 degraders as therapeutics in cancer and inflammatory diseases |
| US20230158158A1 (en) * | 2020-03-27 | 2023-05-25 | Uppthera | Pyrazolo quinazoline derivative compounds inducing selective degradation of plk1 |
| WO2022145989A1 (ko) * | 2020-12-31 | 2022-07-07 | (주) 업테라 | 선택적 plk1 억제제로서의 피리미도디아제핀 유도체 |
| CA3228601A1 (en) * | 2021-08-10 | 2023-02-16 | Soo Hee RYU | Novel plk1 degradation inducing compound |
| GB202313514D0 (en) | 2023-09-05 | 2023-10-18 | Cambridge Entpr Ltd | Treatment of inflammatory diseases |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| AU7491400A (en) * | 1999-09-17 | 2001-04-17 | Abbott Gmbh & Co. Kg | Kinase inhibitors as therapeutic agents |
| NZ531928A (en) | 2001-09-04 | 2005-10-28 | Boehringer Ingelheim Pharma | Novel dihydropteridinones, method for producing the same and the use thereof as medicaments |
| KR20080095902A (ko) * | 2006-02-14 | 2008-10-29 | 버텍스 파마슈티칼스 인코포레이티드 | 단백질 키나제의 억제제로서 유용한 디하이드로디아제핀 |
| TW200808325A (en) | 2006-07-06 | 2008-02-16 | Astrazeneca Ab | Novel compounds |
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2008
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- 2008-03-11 CN CN201210030872.3A patent/CN102746175B/zh not_active Expired - Fee Related
- 2008-03-11 BR BRPI0809088-2A patent/BRPI0809088A2/pt not_active IP Right Cessation
- 2008-03-11 CN CN2008800088890A patent/CN101636399B/zh not_active Expired - Fee Related
- 2008-03-11 AU AU2008228303A patent/AU2008228303B2/en not_active Ceased
- 2008-03-11 AT AT08717594T patent/ATE524472T1/de active
- 2008-03-11 HR HR20110807T patent/HRP20110807T1/hr unknown
- 2008-03-11 PL PL08717594T patent/PL2139892T3/pl unknown
- 2008-03-11 EP EP08717594A patent/EP2139892B1/en not_active Not-in-force
- 2008-03-11 CA CA002680757A patent/CA2680757A1/en not_active Abandoned
- 2008-03-11 MX MX2009010034A patent/MX2009010034A/es active IP Right Grant
- 2008-03-11 DK DK08717594.9T patent/DK2139892T3/da active
- 2008-03-11 JP JP2009553997A patent/JP5087640B2/ja not_active Expired - Fee Related
- 2008-03-11 WO PCT/EP2008/052847 patent/WO2008113711A1/en not_active Ceased
- 2008-03-11 ES ES08717594T patent/ES2371832T3/es active Active
- 2008-03-11 SI SI200830445T patent/SI2139892T1/sl unknown
- 2008-03-11 KR KR1020097019761A patent/KR101157848B1/ko not_active Expired - Fee Related
- 2008-03-18 CL CL2008000785A patent/CL2008000785A1/es unknown
- 2008-03-19 US US12/051,000 patent/US7517873B2/en not_active Expired - Fee Related
- 2008-03-19 AR ARP080101142A patent/AR065794A1/es unknown
- 2008-03-19 PE PE2011001933A patent/PE20120495A1/es not_active Application Discontinuation
- 2008-03-19 TW TW097109660A patent/TWI363629B/zh not_active IP Right Cessation
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2009
- 2009-08-27 IL IL200617A patent/IL200617A/en not_active IP Right Cessation
-
2011
- 2011-11-30 CY CY20111101174T patent/CY1112102T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP2139892A1 (en) | 2010-01-06 |
| JP2010521514A (ja) | 2010-06-24 |
| CL2008000785A1 (es) | 2009-03-27 |
| KR101157848B1 (ko) | 2012-07-11 |
| HK1139936A1 (en) | 2010-09-30 |
| TWI363629B (en) | 2012-05-11 |
| IL200617A (en) | 2014-02-27 |
| CN101636399B (zh) | 2012-04-18 |
| US20080234255A1 (en) | 2008-09-25 |
| PE20120495A1 (es) | 2012-05-12 |
| MX2009010034A (es) | 2009-10-12 |
| WO2008113711A1 (en) | 2008-09-25 |
| CA2680757A1 (en) | 2008-09-25 |
| SI2139892T1 (sl) | 2011-12-30 |
| AR065794A1 (es) | 2009-07-01 |
| TW200843781A (en) | 2008-11-16 |
| EP2139892B1 (en) | 2011-09-14 |
| CY1112102T1 (el) | 2015-11-04 |
| ATE524472T1 (de) | 2011-09-15 |
| JP5087640B2 (ja) | 2012-12-05 |
| DK2139892T3 (da) | 2011-12-12 |
| BRPI0809088A2 (pt) | 2014-09-09 |
| PT2139892E (pt) | 2011-11-21 |
| CN102746175B (zh) | 2014-01-15 |
| AU2008228303A1 (en) | 2008-09-25 |
| US7517873B2 (en) | 2009-04-14 |
| KR20090119913A (ko) | 2009-11-20 |
| ES2371832T3 (es) | 2012-01-10 |
| IL200617A0 (en) | 2010-05-17 |
| CN101636399A (zh) | 2010-01-27 |
| CN102746175A (zh) | 2012-10-24 |
| PL2139892T3 (pl) | 2012-03-30 |
| HRP20110807T1 (hr) | 2011-12-31 |
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| PC1 | Assignment before grant (sect. 113) |
Owner name: TAKEDA PHARMACEUTICAL COMPANY LIMITED Free format text: FORMER APPLICANT(S): F. HOFFMANN-LA ROCHE AG |
|
| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |