AU2008254319B2 - Triazolyl aminopyrimidine compounds - Google Patents
Triazolyl aminopyrimidine compounds Download PDFInfo
- Publication number
- AU2008254319B2 AU2008254319B2 AU2008254319A AU2008254319A AU2008254319B2 AU 2008254319 B2 AU2008254319 B2 AU 2008254319B2 AU 2008254319 A AU2008254319 A AU 2008254319A AU 2008254319 A AU2008254319 A AU 2008254319A AU 2008254319 B2 AU2008254319 B2 AU 2008254319B2
- Authority
- AU
- Australia
- Prior art keywords
- ethyl
- fluoro
- amino
- mmol
- methyl
- 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
- -1 Triazolyl aminopyrimidine compounds Chemical class 0.000 title claims abstract description 131
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 26
- 201000011510 cancer Diseases 0.000 claims abstract description 15
- 150000001875 compounds Chemical class 0.000 claims description 162
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 54
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 48
- 125000000217 alkyl group Chemical group 0.000 claims description 45
- 238000000034 method Methods 0.000 claims description 40
- 229910052739 hydrogen Inorganic materials 0.000 claims description 38
- 239000001257 hydrogen Substances 0.000 claims description 35
- 150000003839 salts Chemical class 0.000 claims description 28
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
- 125000001153 fluoro group Chemical group F* 0.000 claims description 23
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- 150000002431 hydrogen Chemical group 0.000 claims description 13
- 241000124008 Mammalia Species 0.000 claims description 10
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 10
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 9
- 208000006359 hepatoblastoma Diseases 0.000 claims description 9
- 210000004072 lung Anatomy 0.000 claims description 9
- 201000001441 melanoma Diseases 0.000 claims description 9
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 8
- 210000000481 breast Anatomy 0.000 claims description 8
- 230000002357 endometrial effect Effects 0.000 claims description 8
- 230000002496 gastric effect Effects 0.000 claims description 8
- 208000005017 glioblastoma Diseases 0.000 claims description 8
- 230000002611 ovarian Effects 0.000 claims description 8
- 210000002307 prostate Anatomy 0.000 claims description 8
- 208000033781 Thyroid carcinoma Diseases 0.000 claims description 6
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 201000010106 skin squamous cell carcinoma Diseases 0.000 claims description 6
- 201000002510 thyroid cancer Diseases 0.000 claims description 6
- 208000013077 thyroid gland carcinoma Diseases 0.000 claims description 6
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims description 2
- 125000004267 aziridin-2-yl group Chemical group [H]N1C([H])([H])C1([H])* 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- 201000009030 Carcinoma Diseases 0.000 claims 1
- 206010041823 squamous cell carcinoma Diseases 0.000 claims 1
- 210000001685 thyroid gland Anatomy 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 198
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 119
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 116
- 239000000203 mixture Substances 0.000 description 112
- 239000000243 solution Substances 0.000 description 88
- 125000005605 benzo group Chemical group 0.000 description 86
- 238000003756 stirring Methods 0.000 description 78
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 59
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 56
- 238000002360 preparation method Methods 0.000 description 56
- 239000012141 concentrate Substances 0.000 description 55
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 48
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 45
- KFZMGEQAYNKOFK-UHFFFAOYSA-N isopropyl alcohol Natural products CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 45
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 43
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 40
- 229910052938 sodium sulfate Inorganic materials 0.000 description 40
- 235000011152 sodium sulphate Nutrition 0.000 description 40
- 239000007787 solid Substances 0.000 description 39
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 37
- 210000004027 cell Anatomy 0.000 description 35
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- 238000004440 column chromatography Methods 0.000 description 30
- 239000000284 extract Substances 0.000 description 30
- 239000000543 intermediate Substances 0.000 description 29
- 239000012044 organic layer Substances 0.000 description 28
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 28
- 125000001207 fluorophenyl group Chemical group 0.000 description 27
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
- 239000003921 oil Substances 0.000 description 24
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 22
- 239000011734 sodium Substances 0.000 description 21
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 20
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 20
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 20
- 239000002904 solvent Substances 0.000 description 20
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 19
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 19
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- 239000012043 crude product Substances 0.000 description 14
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 13
- 239000010410 layer Substances 0.000 description 13
- 239000012074 organic phase Substances 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 150000004802 benzothiophens Chemical class 0.000 description 11
- 238000003818 flash chromatography Methods 0.000 description 11
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 11
- 235000019341 magnesium sulphate Nutrition 0.000 description 11
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 10
- 229910052757 nitrogen Inorganic materials 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 239000012071 phase Substances 0.000 description 9
- 238000010791 quenching Methods 0.000 description 9
- 230000002441 reversible effect Effects 0.000 description 9
- 229920006395 saturated elastomer Polymers 0.000 description 9
- 239000000377 silicon dioxide Substances 0.000 description 9
- 108020004414 DNA Proteins 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- 238000005481 NMR spectroscopy Methods 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 230000000394 mitotic effect Effects 0.000 description 8
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 7
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 7
- 239000005457 ice water Substances 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 229910000029 sodium carbonate Inorganic materials 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- OPZDXMCOWFPQPE-UHFFFAOYSA-N 2-bromo-4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C(Br)=C1 OPZDXMCOWFPQPE-UHFFFAOYSA-N 0.000 description 6
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 6
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 6
- 239000000908 ammonium hydroxide Substances 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 6
- 239000003960 organic solvent Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- 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 6
- 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 6
- 208000033962 Fontaine progeroid syndrome Diseases 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 239000012230 colorless oil Substances 0.000 description 5
- 238000005859 coupling reaction Methods 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- CASYPDKXSSJANQ-UHFFFAOYSA-N 1-(2-bromo-4-fluorophenyl)ethanamine Chemical compound CC(N)C1=CC=C(F)C=C1Br CASYPDKXSSJANQ-UHFFFAOYSA-N 0.000 description 4
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 4
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
- 239000005909 Kieselgur Substances 0.000 description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 4
- WGXZDYPGLJYBJW-UHFFFAOYSA-N chloroform;propan-2-ol Chemical compound CC(C)O.ClC(Cl)Cl WGXZDYPGLJYBJW-UHFFFAOYSA-N 0.000 description 4
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 4
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 229940086542 triethylamine Drugs 0.000 description 4
- QUNRYKLHPBGAPI-UHFFFAOYSA-N 1-(2-bromo-4-fluorophenyl)-2,2,2-trifluoroethanol Chemical compound FC(F)(F)C(O)C1=CC=C(F)C=C1Br QUNRYKLHPBGAPI-UHFFFAOYSA-N 0.000 description 3
- BTTNYQZNBZNDOR-UHFFFAOYSA-N 2,4-dichloropyrimidine Chemical compound ClC1=CC=NC(Cl)=N1 BTTNYQZNBZNDOR-UHFFFAOYSA-N 0.000 description 3
- NUKGECOKHDKZAW-UHFFFAOYSA-N 2-(2-bromo-4-fluorophenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)C1=CC=C(F)C=C1Br NUKGECOKHDKZAW-UHFFFAOYSA-N 0.000 description 3
- CHEYEJGXQSHSFE-UHFFFAOYSA-N 2-(triazol-1-yl)ethanamine Chemical compound NCCN1C=CN=N1 CHEYEJGXQSHSFE-UHFFFAOYSA-N 0.000 description 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
- ARTHFCQULHOMMJ-UHFFFAOYSA-N 5-fluoro-4-[7-(5-fluoro-1h-indol-7-yl)-1-benzothiophen-2-yl]-n-[2-(triazol-1-yl)ethyl]pyrimidin-2-amine Chemical compound C=12NC=CC2=CC(F)=CC=1C(C=1S2)=CC=CC=1C=C2C(C(=CN=1)F)=NC=1NCCN1C=CN=N1 ARTHFCQULHOMMJ-UHFFFAOYSA-N 0.000 description 3
- NOICDPBEDNMHQK-UHFFFAOYSA-N 7-bromo-1-benzothiophene Chemical compound BrC1=CC=CC2=C1SC=C2 NOICDPBEDNMHQK-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
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- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 3
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- 238000009833 condensation Methods 0.000 description 3
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- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
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- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 3
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- 230000003389 potentiating effect Effects 0.000 description 3
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- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 3
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- 125000001424 substituent group Chemical group 0.000 description 3
- 125000001010 sulfinic acid amide group Chemical group 0.000 description 3
- LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 3
- CCLKBQZVNSHZLO-UHFFFAOYSA-N tert-butyl n-[2-(2-bromophenyl)ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCC1=CC=CC=C1Br CCLKBQZVNSHZLO-UHFFFAOYSA-N 0.000 description 3
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- AUEGGHBBWKGFRH-UHFFFAOYSA-N tert-butyl n-[1-(2-bromo-4-fluorophenyl)cyclobutyl]carbamate Chemical compound C=1C=C(F)C=C(Br)C=1C1(NC(=O)OC(C)(C)C)CCC1 AUEGGHBBWKGFRH-UHFFFAOYSA-N 0.000 description 1
- MNZCBGMOGKPXCU-UHFFFAOYSA-N tert-butyl n-[1-(2-bromo-4-fluorophenyl)cyclopropyl]carbamate Chemical compound C=1C=C(F)C=C(Br)C=1C1(NC(=O)OC(C)(C)C)CC1 MNZCBGMOGKPXCU-UHFFFAOYSA-N 0.000 description 1
- KHVYXBFMEJBYTM-UHFFFAOYSA-N tert-butyl n-[1-(2-bromo-4-fluorophenyl)ethyl]-n-methylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)C(C)C1=CC=C(F)C=C1Br KHVYXBFMEJBYTM-UHFFFAOYSA-N 0.000 description 1
- FZJZVHFDACTDDT-UHFFFAOYSA-N tert-butyl n-[1-(2-bromo-4-fluorophenyl)ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(C)C1=CC=C(F)C=C1Br FZJZVHFDACTDDT-UHFFFAOYSA-N 0.000 description 1
- CEKFXLTUELQZBS-UHFFFAOYSA-N tert-butyl n-[1-(2-bromo-4-fluorophenyl)propyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(CC)C1=CC=C(F)C=C1Br CEKFXLTUELQZBS-UHFFFAOYSA-N 0.000 description 1
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- YWIKIZRQWUMSOX-UHFFFAOYSA-N tert-butyl n-[2-(2-bromo-4-fluorophenyl)-2-hydroxyethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC(O)C1=CC=C(F)C=C1Br YWIKIZRQWUMSOX-UHFFFAOYSA-N 0.000 description 1
- SINBAJJBBVBXLB-UHFFFAOYSA-N tert-butyl n-[2-[2-(1-benzothiophen-7-yl)-4-fluorophenoxy]ethyl]-n-methylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)CCOC1=CC=C(F)C=C1C1=CC=CC2=C1SC=C2 SINBAJJBBVBXLB-UHFFFAOYSA-N 0.000 description 1
- MDGMYIZXXAVMSU-UHFFFAOYSA-N tert-butyl n-[2-[2-(1-benzothiophen-7-yl)phenoxy]ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCOC1=CC=CC=C1C1=CC=CC2=C1SC=C2 MDGMYIZXXAVMSU-UHFFFAOYSA-N 0.000 description 1
- DJFYXCGXQHJTJC-UHFFFAOYSA-N tert-butyl n-[[2-[2-[5-fluoro-2-[2-(triazol-1-yl)ethylamino]pyrimidin-4-yl]-1-benzothiophen-7-yl]phenyl]methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1=CC=CC=C1C1=CC=CC2=C1SC(C=1C(=CN=C(NCCN3N=NC=C3)N=1)F)=C2 DJFYXCGXQHJTJC-UHFFFAOYSA-N 0.000 description 1
- JHLVEBNWCCKSGY-UHFFFAOYSA-N tert-butyl n-methylcarbamate Chemical compound CNC(=O)OC(C)(C)C JHLVEBNWCCKSGY-UHFFFAOYSA-N 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- GMRIOAVKKGNMMV-UHFFFAOYSA-N tetrabutylazanium;azide Chemical compound [N-]=[N+]=[N-].CCCC[N+](CCCC)(CCCC)CCCC GMRIOAVKKGNMMV-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
- A61K31/495—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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US93834707P | 2007-05-16 | 2007-05-16 | |
| US60/938,347 | 2007-05-16 | ||
| PCT/US2008/062808 WO2008144223A2 (en) | 2007-05-16 | 2008-05-07 | Triazolyl aminopyrimidine compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2008254319A1 AU2008254319A1 (en) | 2008-11-27 |
| AU2008254319B2 true AU2008254319B2 (en) | 2012-04-19 |
Family
ID=39951591
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2008254319A Ceased AU2008254319B2 (en) | 2007-05-16 | 2008-05-07 | Triazolyl aminopyrimidine compounds |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US8063035B2 (OSRAM) |
| EP (1) | EP2155734A2 (OSRAM) |
| JP (1) | JP5248600B2 (OSRAM) |
| KR (1) | KR101131261B1 (OSRAM) |
| CN (1) | CN101679395B (OSRAM) |
| AR (1) | AR066473A1 (OSRAM) |
| AU (1) | AU2008254319B2 (OSRAM) |
| BR (1) | BRPI0811433A2 (OSRAM) |
| CA (1) | CA2691997A1 (OSRAM) |
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| PE (1) | PE20090216A1 (OSRAM) |
| TW (1) | TW200908981A (OSRAM) |
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Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7964729B2 (en) | 2006-08-28 | 2011-06-21 | Massachusetts Institute Of Technology | Sox-based kinase sensor |
| CN101563342B (zh) | 2006-12-21 | 2012-09-05 | 伊莱利利公司 | 用于治疗癌症的咪唑啉酮基氨基嘧啶化合物 |
| US8063212B2 (en) | 2006-12-21 | 2011-11-22 | Eli Lilly And Company | Imidazolidinonyl aminopyrimidine compounds for the treatment of cancer |
| US8440835B2 (en) | 2007-02-26 | 2013-05-14 | Massachusetts Institute Of Technology | Environmentally sensitive fluorophores |
| MX2009012228A (es) | 2007-05-16 | 2009-12-01 | Lilly Co Eli | Compuesto de triazolil aminopirimidina. |
| PE20090803A1 (es) | 2007-05-16 | 2009-07-11 | Lilly Co Eli | Compuestos triazolil aminopirimidin como inhibidores de plk1 |
| KR101123178B1 (ko) * | 2009-04-09 | 2012-06-13 | (주)에스메디 | 2-아릴벤조싸이오펜 유도체 또는 이의 약학적으로 허용가능한 염, 이의 제조방법 및 이를 유효성분으로 함유하는 퇴행성 뇌질환의 진단 또는 치료용 약학적 조성물 |
| CN102597236A (zh) * | 2009-08-25 | 2012-07-18 | 肿瘤疗法科学股份有限公司 | 癌症治疗和诊断的靶基因ercc6l |
| WO2011025546A1 (en) * | 2009-08-31 | 2011-03-03 | Massachusetts Institute Of Technology | 1, 2, 3-triazole containing protein kinase sensors |
| UA119247C2 (uk) | 2013-09-06 | 2019-05-27 | РОЙВЕНТ САЙЕНСИЗ ҐмбГ | Спіроциклічні сполуки як інгібітори триптофангідроксилази |
| US9611201B2 (en) * | 2015-03-05 | 2017-04-04 | Karos Pharmaceuticals, Inc. | Processes for preparing (R)-1-(5-chloro-[1,1′-biphenyl]-2-yl)-2,2,2-trifluoroethanol and 1-(5-chloro-[1,1′-biphenyl]-2-yl)-2,2,2-trifluoroethanone |
| CN109415366B (zh) * | 2016-06-23 | 2022-02-22 | 豪夫迈·罗氏有限公司 | [1,2,3]三唑并[4,5-d]嘧啶衍生物 |
| WO2020068600A1 (en) * | 2018-09-24 | 2020-04-02 | Rapt Therapeutics, Inc. | Ubiquitin-specific-processing protease 7 (usp7) modulators and uses thereof |
| BR112022004030A2 (pt) * | 2019-09-05 | 2022-05-31 | Univ Melbourne | Método e composição para reduzir a nitrificação, fertilizante e compostos |
| CN112341428A (zh) * | 2020-11-04 | 2021-02-09 | 菏泽鸿特药业有限公司 | 一种噻吩-2-乙胺的生产方法 |
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| WO2006066172A1 (en) * | 2004-12-17 | 2006-06-22 | Amgen, Inc. | Aminopyrimidine compounds and methods of use |
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|---|---|---|---|---|
| US4929726A (en) * | 1988-02-09 | 1990-05-29 | Georgia State University Foundation, Inc. | Novel diazines and their method of preparation |
| WO2004063192A1 (en) | 2003-01-10 | 2004-07-29 | Pharmacopeia Drug Discovery, Inc. | Imidazolyl pyrimidine derivatives useful as il-8 receptor modulators |
| GB0308466D0 (en) | 2003-04-11 | 2003-05-21 | Novartis Ag | Organic compounds |
| JP2007533602A (ja) * | 2003-07-31 | 2007-11-22 | ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド | 置換ベンゾチオフェン化合物及びそれらの使用 |
| TW200800201A (en) | 2005-11-18 | 2008-01-01 | Lilly Co Eli | Pyrimidinyl benzothiophene compounds |
| MX2008012482A (es) | 2006-03-31 | 2008-10-10 | Abbott Lab | Compuestos de indazol. |
| CN101563342B (zh) | 2006-12-21 | 2012-09-05 | 伊莱利利公司 | 用于治疗癌症的咪唑啉酮基氨基嘧啶化合物 |
| US8063212B2 (en) * | 2006-12-21 | 2011-11-22 | Eli Lilly And Company | Imidazolidinonyl aminopyrimidine compounds for the treatment of cancer |
| PE20090803A1 (es) * | 2007-05-16 | 2009-07-11 | Lilly Co Eli | Compuestos triazolil aminopirimidin como inhibidores de plk1 |
| MX2009012228A (es) | 2007-05-16 | 2009-12-01 | Lilly Co Eli | Compuesto de triazolil aminopirimidina. |
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- 2008-05-07 MX MX2009012228A patent/MX2009012228A/es active IP Right Grant
- 2008-05-07 US US12/598,926 patent/US8063035B2/en not_active Expired - Fee Related
- 2008-05-07 CN CN2008800157689A patent/CN101679395B/zh not_active Expired - Fee Related
- 2008-05-07 CL CL2008001323A patent/CL2008001323A1/es unknown
- 2008-05-07 JP JP2010508500A patent/JP5248600B2/ja not_active Expired - Fee Related
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- 2008-05-07 PE PE2008000798A patent/PE20090216A1/es not_active Application Discontinuation
- 2008-05-07 CA CA002691997A patent/CA2691997A1/en not_active Abandoned
- 2008-05-07 EP EP08747731A patent/EP2155734A2/en not_active Withdrawn
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- 2008-05-07 KR KR1020097023340A patent/KR101131261B1/ko not_active Expired - Fee Related
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- 2008-05-07 WO PCT/US2008/062808 patent/WO2008144223A2/en not_active Ceased
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006066172A1 (en) * | 2004-12-17 | 2006-06-22 | Amgen, Inc. | Aminopyrimidine compounds and methods of use |
Also Published As
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|---|---|
| CN101679395A (zh) | 2010-03-24 |
| TW200908981A (en) | 2009-03-01 |
| WO2008144223A3 (en) | 2009-02-05 |
| US8063035B2 (en) | 2011-11-22 |
| AU2008254319A1 (en) | 2008-11-27 |
| JP5248600B2 (ja) | 2013-07-31 |
| CN101679395B (zh) | 2012-06-13 |
| BRPI0811433A2 (pt) | 2016-03-22 |
| KR101131261B1 (ko) | 2012-04-24 |
| MX2009012228A (es) | 2009-12-01 |
| AR066473A1 (es) | 2009-08-19 |
| JP2010527365A (ja) | 2010-08-12 |
| EP2155734A2 (en) | 2010-02-24 |
| KR20090130242A (ko) | 2009-12-21 |
| CA2691997A1 (en) | 2008-11-27 |
| EA200971068A1 (ru) | 2010-04-30 |
| WO2008144223A2 (en) | 2008-11-27 |
| US20100087431A1 (en) | 2010-04-08 |
| CL2008001323A1 (es) | 2009-05-29 |
| EA016781B1 (ru) | 2012-07-30 |
| PE20090216A1 (es) | 2009-02-28 |
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