CA2773661A1 - Ether derivatives of bicyclic heteroaryls - Google Patents
Ether derivatives of bicyclic heteroaryls Download PDFInfo
- Publication number
- CA2773661A1 CA2773661A1 CA2773661A CA2773661A CA2773661A1 CA 2773661 A1 CA2773661 A1 CA 2773661A1 CA 2773661 A CA2773661 A CA 2773661A CA 2773661 A CA2773661 A CA 2773661A CA 2773661 A1 CA2773661 A1 CA 2773661A1
- Authority
- CA
- Canada
- Prior art keywords
- 7alkyl
- mmol
- amino
- pyrrolo
- pyrimidin
- 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.)
- Abandoned
Links
- 125000001072 heteroaryl group Chemical group 0.000 title description 3
- 150000002170 ethers Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 486
- 238000000034 method Methods 0.000 claims abstract description 208
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 73
- 201000010099 disease Diseases 0.000 claims abstract description 52
- 239000003814 drug Substances 0.000 claims abstract description 39
- 238000011282 treatment Methods 0.000 claims abstract description 38
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 18
- -1 C1-7alkyl Chemical group 0.000 claims description 145
- 125000001424 substituent group Chemical group 0.000 claims description 65
- 125000000623 heterocyclic group Chemical group 0.000 claims description 56
- 150000003839 salts Chemical class 0.000 claims description 56
- 229910052739 hydrogen Inorganic materials 0.000 claims description 52
- 239000001257 hydrogen Substances 0.000 claims description 51
- 125000005843 halogen group Chemical group 0.000 claims description 47
- 206010028980 Neoplasm Diseases 0.000 claims description 39
- 229920006395 saturated elastomer Polymers 0.000 claims description 39
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 38
- 125000004429 atom Chemical group 0.000 claims description 37
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 36
- 230000000694 effects Effects 0.000 claims description 29
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 28
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 27
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 23
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
- 230000001404 mediated effect Effects 0.000 claims description 22
- 208000035475 disorder Diseases 0.000 claims description 20
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 20
- 230000005764 inhibitory process Effects 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 16
- 239000003795 chemical substances by application Substances 0.000 claims description 15
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 125000004434 sulfur atom Chemical group 0.000 claims description 11
- 125000002619 bicyclic group Chemical group 0.000 claims description 10
- 125000002950 monocyclic group Chemical group 0.000 claims description 10
- 230000001028 anti-proliverative effect Effects 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 150000002431 hydrogen Chemical group 0.000 claims description 9
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 9
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 8
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 8
- 125000004193 piperazinyl group Chemical group 0.000 claims description 8
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 7
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 6
- 101100516554 Caenorhabditis elegans nhr-5 gene Proteins 0.000 claims description 6
- 101100134922 Gallus gallus COR5 gene Proteins 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 6
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 5
- 201000009030 Carcinoma Diseases 0.000 claims description 5
- 125000002393 azetidinyl group Chemical group 0.000 claims description 5
- 210000004072 lung Anatomy 0.000 claims description 5
- 201000008968 osteosarcoma Diseases 0.000 claims description 5
- 230000002611 ovarian Effects 0.000 claims description 5
- 210000002307 prostate Anatomy 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 210000001685 thyroid gland Anatomy 0.000 claims description 5
- 208000026310 Breast neoplasm Diseases 0.000 claims description 4
- 125000003725 azepanyl group Chemical group 0.000 claims description 4
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 201000001441 melanoma Diseases 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000002757 morpholinyl group Chemical group 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 3
- 208000002699 Digestive System Neoplasms Diseases 0.000 claims description 3
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 3
- 208000034578 Multiple myelomas Diseases 0.000 claims description 3
- 206010029260 Neuroblastoma Diseases 0.000 claims description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 3
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 3
- 206010069351 acute lung injury Diseases 0.000 claims description 3
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 208000020816 lung neoplasm Diseases 0.000 claims description 3
- 208000037841 lung tumor Diseases 0.000 claims description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
- 201000002528 pancreatic cancer Diseases 0.000 claims description 3
- 125000003386 piperidinyl group Chemical group 0.000 claims description 3
- 208000023958 prostate neoplasm Diseases 0.000 claims description 3
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- 208000013076 thyroid tumor Diseases 0.000 claims description 3
- 208000025421 tumor of uterus Diseases 0.000 claims description 3
- 206010046766 uterine cancer Diseases 0.000 claims description 3
- CBQODGRJHHJAEC-UHFFFAOYSA-N 5-[3-(7-oxabicyclo[2.2.1]heptan-4-ylmethoxy)phenyl]-7-[3-[(1-oxo-1,4-thiazinan-4-yl)methyl]cyclobutyl]pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=C(C=2C=C(OCC34CCC(CC3)O4)C=CC=2)C=2C(N)=NC=NC=2N1C(C1)CC1CN1CCS(=O)CC1 CBQODGRJHHJAEC-UHFFFAOYSA-N 0.000 claims description 2
- SWSPMOBRMONVHC-UHFFFAOYSA-N 7-[3-[(1,1-dioxo-1,4-thiazinan-4-yl)methyl]cyclobutyl]-5-[3-(7-oxabicyclo[2.2.1]heptan-4-ylmethoxy)phenyl]pyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=C(C=2C=C(OCC34CCC(CC3)O4)C=CC=2)C=2C(N)=NC=NC=2N1C(C1)CC1CN1CCS(=O)(=O)CC1 SWSPMOBRMONVHC-UHFFFAOYSA-N 0.000 claims description 2
- FMTQHAXNHBODDV-FYWDEPLMSA-N C1CN(C(=O)C)CCN1[C@@H]1C[C@H](N2C3=NC=NC(N)=C3C(C=3C=C(OCC45CCC(CC4)O5)C=CC=3)=C2)C1 Chemical compound C1CN(C(=O)C)CCN1[C@@H]1C[C@H](N2C3=NC=NC(N)=C3C(C=3C=C(OCC45CCC(CC4)O5)C=CC=3)=C2)C1 FMTQHAXNHBODDV-FYWDEPLMSA-N 0.000 claims description 2
- 101100294115 Caenorhabditis elegans nhr-4 gene Proteins 0.000 claims description 2
- 208000006168 Ewing Sarcoma Diseases 0.000 claims description 2
- SICHDGGOWKHCOA-ABPGQXKISA-N N1([C@H]2C[C@H](C2)N2C=3N=CN=C(C=3C(C=3C=C(OCC45CCC(CC4)O5)C=CC=3)=C2)N)CCS(=O)(=O)CC1 Chemical compound N1([C@H]2C[C@H](C2)N2C=3N=CN=C(C=3C(C=3C=C(OCC45CCC(CC4)O5)C=CC=3)=C2)N)CCS(=O)(=O)CC1 SICHDGGOWKHCOA-ABPGQXKISA-N 0.000 claims description 2
- KCANTRHVPWYUAW-ABPGQXKISA-N N1([C@H]2C[C@H](C2)N2C=3N=CN=C(C=3C(C=3C=C(OCC45CCC(CC4)O5)C=CC=3)=C2)N)CCS(=O)CC1 Chemical compound N1([C@H]2C[C@H](C2)N2C=3N=CN=C(C=3C(C=3C=C(OCC45CCC(CC4)O5)C=CC=3)=C2)N)CCS(=O)CC1 KCANTRHVPWYUAW-ABPGQXKISA-N 0.000 claims description 2
- YJHXUGJSFWZTRI-UVHVAUBXSA-N NC(=O)[C@H]1CCCN1C[C@@H]1C[C@@H](N2C3=NC=NC(N)=C3C(C=3C=C(OCC45CCC(CC4)O5)C=CC=3)=C2)C1 Chemical compound NC(=O)[C@H]1CCCN1C[C@@H]1C[C@@H](N2C3=NC=NC(N)=C3C(C=3C=C(OCC45CCC(CC4)O5)C=CC=3)=C2)C1 YJHXUGJSFWZTRI-UVHVAUBXSA-N 0.000 claims description 2
- YJHXUGJSFWZTRI-XZMHDNNLSA-N NC(=O)[C@H]1CCCN1C[C@@H]1C[C@H](N2C3=NC=NC(N)=C3C(C=3C=C(OCC45CCC(CC4)O5)C=CC=3)=C2)C1 Chemical compound NC(=O)[C@H]1CCCN1C[C@@H]1C[C@H](N2C3=NC=NC(N)=C3C(C=3C=C(OCC45CCC(CC4)O5)C=CC=3)=C2)C1 YJHXUGJSFWZTRI-XZMHDNNLSA-N 0.000 claims description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 6
- 125000006563 (C1-3) alkylaminocarbonyl group Chemical group 0.000 claims 1
- IXDDSQBFYZXHOB-MUABAYHSSA-N C1CN(S(=O)(=O)C)CCN1[C@@H]1C[C@H](N2C3=NC=NC(N)=C3C(C=3C=C(OCC45CCC(CC4)O5)C=CC=3)=C2)C1 Chemical compound C1CN(S(=O)(=O)C)CCN1[C@@H]1C[C@H](N2C3=NC=NC(N)=C3C(C=3C=C(OCC45CCC(CC4)O5)C=CC=3)=C2)C1 IXDDSQBFYZXHOB-MUABAYHSSA-N 0.000 claims 1
- YJHXUGJSFWZTRI-RZUKLDMISA-N NC(=O)[C@@H]1CCCN1C[C@@H]1C[C@@H](N2C3=NC=NC(N)=C3C(C=3C=C(OCC45CCC(CC4)O5)C=CC=3)=C2)C1 Chemical compound NC(=O)[C@@H]1CCCN1C[C@@H]1C[C@@H](N2C3=NC=NC(N)=C3C(C=3C=C(OCC45CCC(CC4)O5)C=CC=3)=C2)C1 YJHXUGJSFWZTRI-RZUKLDMISA-N 0.000 claims 1
- XAAOIYDRJJVHEG-UHFFFAOYSA-N methyl n-[[3-[4-amino-5-[3-(7-oxabicyclo[2.2.1]heptan-4-ylmethoxy)phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclobutyl]methyl]carbamate Chemical compound C1C(CNC(=O)OC)CC1N1C2=NC=NC(N)=C2C(C=2C=C(OCC34CCC(CC3)O4)C=CC=2)=C1 XAAOIYDRJJVHEG-UHFFFAOYSA-N 0.000 claims 1
- 230000008569 process Effects 0.000 abstract description 29
- 238000002360 preparation method Methods 0.000 abstract description 9
- 230000002062 proliferating effect Effects 0.000 abstract description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 383
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 360
- 239000000543 intermediate Substances 0.000 description 216
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 207
- 239000000203 mixture Substances 0.000 description 162
- 235000013350 formula milk Nutrition 0.000 description 149
- 239000011541 reaction mixture Substances 0.000 description 132
- 229910001868 water Inorganic materials 0.000 description 107
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 105
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 101
- 239000000243 solution Substances 0.000 description 95
- 235000019439 ethyl acetate Nutrition 0.000 description 78
- 229910052938 sodium sulfate Inorganic materials 0.000 description 78
- 235000011152 sodium sulphate Nutrition 0.000 description 78
- 238000006243 chemical reaction Methods 0.000 description 73
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 73
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 69
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 67
- 239000007787 solid Substances 0.000 description 66
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical class CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 62
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 62
- 238000004128 high performance liquid chromatography Methods 0.000 description 61
- 239000012044 organic layer Substances 0.000 description 58
- 239000012267 brine Substances 0.000 description 56
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 53
- 239000007832 Na2SO4 Substances 0.000 description 53
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 46
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 43
- 238000010898 silica gel chromatography Methods 0.000 description 43
- 238000005160 1H NMR spectroscopy Methods 0.000 description 41
- 229940093499 ethyl acetate Drugs 0.000 description 40
- 239000003921 oil Substances 0.000 description 39
- 235000019198 oils Nutrition 0.000 description 39
- FLDSMVTWEZKONL-AWEZNQCLSA-N 5,5-dimethyl-N-[(3S)-5-methyl-4-oxo-2,3-dihydro-1,5-benzoxazepin-3-yl]-1,4,7,8-tetrahydrooxepino[4,5-c]pyrazole-3-carboxamide Chemical compound CC1(CC2=C(NN=C2C(=O)N[C@@H]2C(N(C3=C(OC2)C=CC=C3)C)=O)CCO1)C FLDSMVTWEZKONL-AWEZNQCLSA-N 0.000 description 37
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 37
- 238000003818 flash chromatography Methods 0.000 description 37
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 36
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 36
- 235000017557 sodium bicarbonate Nutrition 0.000 description 34
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 34
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 33
- 238000003756 stirring Methods 0.000 description 33
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 30
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- 238000000746 purification Methods 0.000 description 30
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- 238000005481 NMR spectroscopy Methods 0.000 description 26
- 125000000217 alkyl group Chemical group 0.000 description 26
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 25
- 239000002904 solvent Substances 0.000 description 25
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 25
- 238000007792 addition Methods 0.000 description 24
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 23
- 108010031794 IGF Type 1 Receptor Proteins 0.000 description 23
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 23
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- 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 description 22
- 125000004043 oxo group Chemical group O=* 0.000 description 21
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 20
- 238000001816 cooling Methods 0.000 description 20
- 239000007858 starting material Substances 0.000 description 20
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- 229910052943 magnesium sulfate Inorganic materials 0.000 description 19
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 19
- 229940124597 therapeutic agent Drugs 0.000 description 19
- 238000004809 thin layer chromatography Methods 0.000 description 19
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
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- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 16
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- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 13
- 241000124008 Mammalia Species 0.000 description 12
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
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- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
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- 229910052757 nitrogen Inorganic materials 0.000 description 11
- 125000006239 protecting group Chemical group 0.000 description 11
- 230000004663 cell proliferation Effects 0.000 description 10
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 10
- 238000010348 incorporation Methods 0.000 description 10
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- JXLYSJRDGCGARV-CFWMRBGOSA-N vinblastine Chemical compound C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-CFWMRBGOSA-N 0.000 description 1
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- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
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Classifications
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- 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
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
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- A61K9/2022—Organic macromolecular compounds
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
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- Inorganic Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Pulmonology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
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| US24118209P | 2009-09-10 | 2009-09-10 | |
| US61/241,182 | 2009-09-10 | ||
| PCT/EP2010/063334 WO2011029915A1 (en) | 2009-09-10 | 2010-09-10 | Ether derivatives of bicyclic heteroaryls |
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| CA2773661A1 true CA2773661A1 (en) | 2011-03-17 |
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| WO2011146313A1 (en) | 2010-05-19 | 2011-11-24 | The University Of North Carolina At Chapel Hill | Pyrazolopyrimidine compounds for the treatment of cancer |
| EP2763988B1 (en) | 2011-10-03 | 2017-09-20 | The University of North Carolina At Chapel Hill | Pyrrolopyrimidine compounds for the treatment of cancer |
| CA2863239C (en) * | 2012-01-31 | 2016-09-13 | Beta Pharma Canada Inc. | Cyclic molecules as bruton's tyrosine kinase inhibitors |
| TW201348231A (zh) | 2012-02-29 | 2013-12-01 | Amgen Inc | 雜雙環化合物 |
| BR112014028424A2 (pt) | 2012-05-22 | 2018-04-24 | Univ North Carolina Chapel Hill | compostos de pirimidina para o tratamento de câncer |
| EP2909211A4 (en) | 2012-10-17 | 2016-06-22 | Univ North Carolina | PYRAZOLOPYRIMIDINE COMPOUNDS FOR CANCER TREATMENT |
| AU2013344049B2 (en) | 2012-11-06 | 2017-12-21 | Fochon Pharmaceuticals, Ltd. | ALK kinase inhibitors |
| US9771330B2 (en) | 2012-11-27 | 2017-09-26 | The University Of North Carolina At Chapel Hill | Pyrimidine compounds for the treatment of cancer |
| JP2017513942A (ja) | 2014-04-11 | 2017-06-01 | ザ・ユニヴァーシティ・オヴ・ノース・キャロライナ・アト・チャペル・ヒル | Ｍｅｒｔｋ特異的ピロロピリミジン化合物 |
| CN108883103A (zh) * | 2015-12-02 | 2018-11-23 | 阿斯特来亚治疗有限责任公司 | 哌啶基痛敏肽受体化合物 |
| US10112924B2 (en) | 2015-12-02 | 2018-10-30 | Astraea Therapeutics, Inc. | Piperdinyl nociceptin receptor compounds |
| US10709708B2 (en) | 2016-03-17 | 2020-07-14 | The University Of North Carolina At Chapel Hill | Method of treating cancer with a combination of MER tyrosine kinase inhibitor and an epidermal growth factor receptor (EGFR) inhibitor |
| CN106008527B (zh) | 2016-06-29 | 2018-05-15 | 四川大学华西医院 | 吡唑并[3,4-d]嘧啶衍生物 |
| CN107098909B (zh) * | 2017-05-19 | 2019-02-22 | 四川大学华西医院 | 烷氧端基寡peg修饰的氨基嘧啶衍生物及抗肿瘤应用 |
| CN115916966A (zh) | 2020-01-30 | 2023-04-04 | 加利福尼亚大学董事会 | Strad结合剂及其用途 |
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| EP0100172B1 (en) | 1982-07-23 | 1987-08-12 | Imperial Chemical Industries Plc | Amide derivatives |
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| US5010099A (en) | 1989-08-11 | 1991-04-23 | Harbor Branch Oceanographic Institution, Inc. | Discodermolide compounds, compositions containing same and method of preparation and use |
| NZ243082A (en) | 1991-06-28 | 1995-02-24 | Ici Plc | 4-anilino-quinazoline derivatives; pharmaceutical compositions, preparatory processes, and use thereof |
| GB9300059D0 (en) | 1992-01-20 | 1993-03-03 | Zeneca Ltd | Quinazoline derivatives |
| TW225528B (c_deeref_Disk_and_Scratch_Disk_Pools_and_Their_Defaults.html) | 1992-04-03 | 1994-06-21 | Ciba Geigy Ag | |
| EP1238986B1 (en) | 1992-10-28 | 2008-06-25 | Genentech, Inc. | Use of Vascular endothelial cell growth factor antagonists |
| CN1046731C (zh) | 1994-09-29 | 1999-11-24 | 诺瓦蒂斯有限公司 | 吡咯并[2,3-d]嘧啶类化合物及其应用 |
| GB9508538D0 (en) | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
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| US5843901A (en) | 1995-06-07 | 1998-12-01 | Advanced Research & Technology Institute | LHRH antagonist peptides |
| ATE212993T1 (de) | 1995-07-06 | 2002-02-15 | Novartis Erfind Verwalt Gmbh | Pyrolopyrimidine und verfahren zu ihrer herstellung |
| GB9517060D0 (en) | 1995-08-17 | 1995-10-25 | Ciba Geigy Ag | Acylated oligopeptide derivatives |
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-
2010
- 2010-09-10 MX MX2012002997A patent/MX2012002997A/es not_active Application Discontinuation
- 2010-09-10 BR BR112012005400A patent/BR112012005400A2/pt not_active Application Discontinuation
- 2010-09-10 IN IN2139DEN2012 patent/IN2012DN02139A/en unknown
- 2010-09-10 JP JP2012528376A patent/JP2013504543A/ja active Pending
- 2010-09-10 CA CA2773661A patent/CA2773661A1/en not_active Abandoned
- 2010-09-10 EA EA201200471A patent/EA201200471A1/ru unknown
- 2010-09-10 KR KR1020127009095A patent/KR20120093867A/ko not_active Withdrawn
- 2010-09-10 AU AU2010294209A patent/AU2010294209A1/en not_active Abandoned
- 2010-09-10 CN CN2010800506564A patent/CN102596963A/zh active Pending
- 2010-09-10 US US13/394,534 patent/US20120165310A1/en not_active Abandoned
- 2010-09-10 WO PCT/EP2010/063334 patent/WO2011029915A1/en active Application Filing
- 2010-09-10 EP EP10763143A patent/EP2475668A1/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| AU2010294209A1 (en) | 2012-03-29 |
| BR112012005400A2 (pt) | 2016-04-05 |
| EA201200471A1 (ru) | 2012-10-30 |
| MX2012002997A (es) | 2012-08-01 |
| KR20120093867A (ko) | 2012-08-23 |
| CN102596963A (zh) | 2012-07-18 |
| WO2011029915A1 (en) | 2011-03-17 |
| JP2013504543A (ja) | 2013-02-07 |
| US20120165310A1 (en) | 2012-06-28 |
| IN2012DN02139A (c_deeref_Disk_and_Scratch_Disk_Pools_and_Their_Defaults.html) | 2015-08-07 |
| EP2475668A1 (en) | 2012-07-18 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20140910 |