CA2665736A1 - Pteridine derivatives as polo-like kinase inhibitors useful in the treatment of cancer - Google Patents
Pteridine derivatives as polo-like kinase inhibitors useful in the treatment of cancer Download PDFInfo
- Publication number
- CA2665736A1 CA2665736A1 CA002665736A CA2665736A CA2665736A1 CA 2665736 A1 CA2665736 A1 CA 2665736A1 CA 002665736 A CA002665736 A CA 002665736A CA 2665736 A CA2665736 A CA 2665736A CA 2665736 A1 CA2665736 A1 CA 2665736A1
- Authority
- CA
- Canada
- Prior art keywords
- amino
- cyclopentyl
- ethyl
- methyl
- oxo
- 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
- 206010028980 Neoplasm Diseases 0.000 title claims description 10
- 201000011510 cancer Diseases 0.000 title description 4
- 239000002770 polo like kinase inhibitor Substances 0.000 title description 2
- 125000001042 pteridinyl group Chemical class N1=C(N=CC2=NC=CN=C12)* 0.000 title 1
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 113
- 150000001875 compounds Chemical class 0.000 claims abstract description 81
- 239000001257 hydrogen Substances 0.000 claims abstract description 58
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 27
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 22
- 125000006413 ring segment Chemical group 0.000 claims abstract description 20
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 14
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 13
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 11
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 11
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 11
- 201000010099 disease Diseases 0.000 claims abstract description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 11
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 9
- 230000002062 proliferating effect Effects 0.000 claims abstract description 7
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 6
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 4
- 150000002367 halogens Chemical group 0.000 claims abstract description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract 2
- -1 heterocyclic radical Chemical class 0.000 claims description 114
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 94
- 238000000034 method Methods 0.000 claims description 81
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 53
- 239000000203 mixture Substances 0.000 claims description 40
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 35
- 150000003254 radicals Chemical group 0.000 claims description 32
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
- 102100031463 Serine/threonine-protein kinase PLK1 Human genes 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- 108010056274 polo-like kinase 1 Proteins 0.000 claims description 20
- 230000000694 effects Effects 0.000 claims description 19
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 19
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 125000002950 monocyclic group Chemical group 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 13
- 108010051152 Carboxylesterase Proteins 0.000 claims description 11
- 102000013392 Carboxylesterase Human genes 0.000 claims description 11
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 11
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 11
- 230000003834 intracellular effect Effects 0.000 claims description 11
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 10
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 10
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 8
- 125000001153 fluoro group Chemical group F* 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- 150000001204 N-oxides Chemical class 0.000 claims description 7
- 230000005764 inhibitory process Effects 0.000 claims description 7
- 239000012453 solvate Substances 0.000 claims description 7
- 125000002527 bicyclic carbocyclic group Chemical group 0.000 claims description 6
- 125000004185 ester group Chemical group 0.000 claims description 6
- 125000002843 carboxylic acid group Chemical group 0.000 claims description 5
- 125000001072 heteroaryl group Chemical group 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000004976 cyclobutylene group Chemical group 0.000 claims description 4
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000002837 carbocyclic group Chemical group 0.000 claims description 3
- 125000004956 cyclohexylene group Chemical group 0.000 claims description 3
- 125000004979 cyclopentylene group Chemical group 0.000 claims description 3
- 125000004980 cyclopropylene group Chemical group 0.000 claims description 3
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 3
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000005550 pyrazinylene group Chemical group 0.000 claims description 3
- 125000005551 pyridylene group Chemical group 0.000 claims description 3
- 125000005576 pyrimidinylene group Chemical group 0.000 claims description 3
- 150000003568 thioethers Chemical class 0.000 claims description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims description 2
- DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 claims description 2
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 150000004677 hydrates Chemical class 0.000 claims description 2
- 238000001727 in vivo Methods 0.000 claims description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 2
- 230000001404 mediated effect Effects 0.000 claims description 2
- 125000006203 morpholinoethyl group Chemical group [H]C([H])(*)C([H])([H])N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 101100490437 Mus musculus Acvrl1 gene Proteins 0.000 claims 3
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 1
- 125000006590 (C2-C6) alkenylene group Chemical group 0.000 claims 1
- SYGWYBOJXOGMRU-UHFFFAOYSA-N chembl233051 Chemical group C1=CC=C2C3=CC(C(N(CCN(C)C)C4=O)=O)=C5C4=CC=CC5=C3SC2=C1 SYGWYBOJXOGMRU-UHFFFAOYSA-N 0.000 claims 1
- JYRXAFPCVZFBPK-LMSSTIIKSA-N cyclopentyl (2s)-2-amino-4-[4-[[4-[[(7r)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7h-pteridin-2-yl]amino]-3-fluorobenzoyl]amino]piperidin-1-yl]butanoate Chemical compound N1([C@@H](C(N(C)C2=CN=C(NC=3C(=CC(=CC=3)C(=O)NC3CCN(CC[C@H](N)C(=O)OC4CCCC4)CC3)F)N=C21)=O)CC)C1CCCC1 JYRXAFPCVZFBPK-LMSSTIIKSA-N 0.000 claims 1
- BLLPVQOVERSBPQ-LMSSTIIKSA-N cyclopentyl (2s)-2-amino-4-[4-[[4-[[(7r)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7h-pteridin-2-yl]amino]-3-methoxybenzoyl]amino]piperidin-1-yl]butanoate Chemical compound N1([C@@H](C(N(C)C2=CN=C(NC=3C(=CC(=CC=3)C(=O)NC3CCN(CC[C@H](N)C(=O)OC4CCCC4)CC3)OC)N=C21)=O)CC)C1CCCC1 BLLPVQOVERSBPQ-LMSSTIIKSA-N 0.000 claims 1
- VHUSOKKTOSGZQD-MFMCTBQISA-N cyclopentyl (2s)-2-amino-4-[4-[[4-[[(7r)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7h-pteridin-2-yl]amino]-3-methylbenzoyl]amino]piperidin-1-yl]butanoate Chemical compound N1([C@@H](C(N(C)C2=CN=C(NC=3C(=CC(=CC=3)C(=O)NC3CCN(CC[C@H](N)C(=O)OC4CCCC4)CC3)C)N=C21)=O)CC)C1CCCC1 VHUSOKKTOSGZQD-MFMCTBQISA-N 0.000 claims 1
- FYNNIUGJUPPQKU-SSYAZFEXSA-N cyclopentyl 4-[2-[[4-[[(7r)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7h-pteridin-2-yl]amino]-3-methoxybenzoyl]amino]ethyl]piperazine-2-carboxylate Chemical compound N1([C@@H](C(N(C)C2=CN=C(NC=3C(=CC(=CC=3)C(=O)NCCN3CC(NCC3)C(=O)OC3CCCC3)OC)N=C21)=O)CC)C1CCCC1 FYNNIUGJUPPQKU-SSYAZFEXSA-N 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- ZWVRGHPOLZDMAX-AHKZPQOWSA-N tert-butyl (2s)-2-amino-4-[4-[[4-[[(7r)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7h-pteridin-2-yl]amino]-3-fluorobenzoyl]amino]piperidin-1-yl]butanoate Chemical compound N1([C@@H](C(N(C)C2=CN=C(NC=3C(=CC(=CC=3)C(=O)NC3CCN(CC[C@H](N)C(=O)OC(C)(C)C)CC3)F)N=C21)=O)CC)C1CCCC1 ZWVRGHPOLZDMAX-AHKZPQOWSA-N 0.000 claims 1
- FELPVSBPDABUJB-AHKZPQOWSA-N tert-butyl (2s)-2-amino-4-[4-[[4-[[(7r)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7h-pteridin-2-yl]amino]-3-methoxybenzoyl]amino]piperidin-1-yl]butanoate Chemical compound N1([C@@H](C(N(C)C2=CN=C(NC=3C(=CC(=CC=3)C(=O)NC3CCN(CC[C@H](N)C(=O)OC(C)(C)C)CC3)OC)N=C21)=O)CC)C1CCCC1 FELPVSBPDABUJB-AHKZPQOWSA-N 0.000 claims 1
- WYKSTTZSADEHPC-XTEPFMGCSA-N tert-butyl (2s)-2-amino-4-[4-[[4-[[(7r)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7h-pteridin-2-yl]amino]-3-methylbenzoyl]amino]piperidin-1-yl]butanoate Chemical compound N1([C@@H](C(N(C)C2=CN=C(NC=3C(=CC(=CC=3)C(=O)NC3CCN(CC[C@H](N)C(=O)OC(C)(C)C)CC3)C)N=C21)=O)CC)C1CCCC1 WYKSTTZSADEHPC-XTEPFMGCSA-N 0.000 claims 1
- INSOZCCNGSOCHB-WUBHUQEYSA-N tert-butyl 4-[2-[[4-[[(7r)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7h-pteridin-2-yl]amino]-3-methoxybenzoyl]amino]ethyl]piperazine-2-carboxylate Chemical compound N1([C@@H](C(N(C)C2=CN=C(NC=3C(=CC(=CC=3)C(=O)NCCN3CC(NCC3)C(=O)OC(C)(C)C)OC)N=C21)=O)CC)C1CCCC1 INSOZCCNGSOCHB-WUBHUQEYSA-N 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 abstract description 16
- 101000582926 Dictyostelium discoideum Probable serine/threonine-protein kinase PLK Proteins 0.000 abstract description 10
- 235000008206 alpha-amino acids Nutrition 0.000 abstract description 4
- 125000003275 alpha amino acid group Chemical group 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 182
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 142
- 239000000543 intermediate Substances 0.000 description 138
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 100
- 230000002829 reductive effect Effects 0.000 description 96
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 90
- 239000000243 solution Substances 0.000 description 87
- 235000019439 ethyl acetate Nutrition 0.000 description 71
- 239000011541 reaction mixture Substances 0.000 description 64
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 62
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 58
- 239000000047 product Substances 0.000 description 54
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 52
- 235000019341 magnesium sulphate Nutrition 0.000 description 50
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 48
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 48
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 47
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 46
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 44
- 239000012044 organic layer Substances 0.000 description 43
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 39
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
- 238000006243 chemical reaction Methods 0.000 description 37
- 239000003921 oil Substances 0.000 description 37
- 235000019198 oils Nutrition 0.000 description 37
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 37
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 36
- 239000007787 solid Substances 0.000 description 33
- ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Natural products CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- 238000005481 NMR spectroscopy Methods 0.000 description 31
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
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- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 28
- 125000000217 alkyl group Chemical group 0.000 description 25
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 24
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 23
- 238000000746 purification Methods 0.000 description 23
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- 239000012267 brine Substances 0.000 description 22
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
- 150000002148 esters Chemical class 0.000 description 19
- 235000017557 sodium bicarbonate Nutrition 0.000 description 19
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- 239000012298 atmosphere Substances 0.000 description 18
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 16
- 239000002253 acid Substances 0.000 description 16
- XCIXKGXIYUWCLL-UHFFFAOYSA-N cyclopentanol Chemical compound OC1CCCC1 XCIXKGXIYUWCLL-UHFFFAOYSA-N 0.000 description 16
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- 229940024606 amino acid Drugs 0.000 description 9
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
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- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 7
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 7
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- LQGDKFVWDXOYDG-NSHDSACASA-N cyclopentyl (2s)-4-bromo-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoate Chemical compound CC(C)(C)OC(=O)N[C@@H](CCBr)C(=O)OC1CCCC1 LQGDKFVWDXOYDG-NSHDSACASA-N 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 150000002430 hydrocarbons Chemical group 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
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- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
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- IBDSNZLUHYKHQP-UHFFFAOYSA-N sodium;3-oxidodioxaborirane;tetrahydrate Chemical compound O.O.O.O.[Na+].[O-]B1OO1 IBDSNZLUHYKHQP-UHFFFAOYSA-N 0.000 description 1
- JUJBNYBVVQSIOU-UHFFFAOYSA-M sodium;4-[2-(4-iodophenyl)-3-(4-nitrophenyl)tetrazol-2-ium-5-yl]benzene-1,3-disulfonate Chemical compound [Na+].C1=CC([N+](=O)[O-])=CC=C1N1[N+](C=2C=CC(I)=CC=2)=NC(C=2C(=CC(=CC=2)S([O-])(=O)=O)S([O-])(=O)=O)=N1 JUJBNYBVVQSIOU-UHFFFAOYSA-M 0.000 description 1
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- QTENRWWVYAAPBI-YCRXJPFRSA-N streptomycin sulfate Chemical compound OS(O)(=O)=O.OS(O)(=O)=O.OS(O)(=O)=O.CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](N=C(N)N)[C@H](O)[C@@H](N=C(N)N)[C@H](O)[C@H]1O.CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](N=C(N)N)[C@H](O)[C@@H](N=C(N)N)[C@H](O)[C@H]1O QTENRWWVYAAPBI-YCRXJPFRSA-N 0.000 description 1
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- 229910052623 talc Inorganic materials 0.000 description 1
- CQXDYHPBXDZWBA-UHFFFAOYSA-N tert-butyl 2,2,2-trichloroethanimidate Chemical compound CC(C)(C)OC(=N)C(Cl)(Cl)Cl CQXDYHPBXDZWBA-UHFFFAOYSA-N 0.000 description 1
- CMIBWIAICVBURI-UHFFFAOYSA-N tert-butyl 3-aminopyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(N)C1 CMIBWIAICVBURI-UHFFFAOYSA-N 0.000 description 1
- LZRDHSFPLUWYAX-UHFFFAOYSA-N tert-butyl 4-aminopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(N)CC1 LZRDHSFPLUWYAX-UHFFFAOYSA-N 0.000 description 1
- NPVVAOURNQDLFS-MTSBXAHESA-N tert-butyl 6-[[4-[[(7r)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7h-pteridin-2-yl]amino]-3-methoxybenzoyl]amino]-3-azabicyclo[3.1.0]hexane-3-carboxylate Chemical compound N1([C@@H](C(N(C)C2=CN=C(NC=3C(=CC(=CC=3)C(=O)NC3C4CN(CC43)C(=O)OC(C)(C)C)OC)N=C21)=O)CC)C1CCCC1 NPVVAOURNQDLFS-MTSBXAHESA-N 0.000 description 1
- UWWZMHWHRBGMIT-UHFFFAOYSA-N tert-butyl 6-amino-3-azabicyclo[3.1.0]hexane-3-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC2C(N)C21 UWWZMHWHRBGMIT-UHFFFAOYSA-N 0.000 description 1
- ACNRTYKOPZDRCO-UHFFFAOYSA-N tert-butyl n-(2-oxoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCC=O ACNRTYKOPZDRCO-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D475/00—Heterocyclic compounds containing pteridine ring systems
- C07D475/02—Heterocyclic compounds containing pteridine ring systems with an oxygen atom directly attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D475/00—Heterocyclic compounds containing pteridine ring 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
- A61K31/495—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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0621205.4 | 2006-10-25 | ||
| GB0621205A GB0621205D0 (en) | 2006-10-25 | 2006-10-25 | Inhibitors of PLK |
| GB0715614.4 | 2007-08-10 | ||
| GB0715614A GB0715614D0 (en) | 2007-08-10 | 2007-08-10 | Inhibitors of plk |
| PCT/GB2007/003998 WO2008050096A1 (en) | 2006-10-25 | 2007-10-19 | Pteridine derivatives as polo-like kinase inhibitors useful in the treatment of cancer |
Publications (1)
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|---|---|
| CA2665736A1 true CA2665736A1 (en) | 2008-05-02 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002665736A Abandoned CA2665736A1 (en) | 2006-10-25 | 2007-10-19 | Pteridine derivatives as polo-like kinase inhibitors useful in the treatment of cancer |
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| US (1) | US20100216802A1 (cg-RX-API-DMAC7.html) |
| EP (1) | EP2079743B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP2010507639A (cg-RX-API-DMAC7.html) |
| KR (1) | KR20090071668A (cg-RX-API-DMAC7.html) |
| AT (1) | ATE542820T1 (cg-RX-API-DMAC7.html) |
| AU (1) | AU2007310604B2 (cg-RX-API-DMAC7.html) |
| BR (1) | BRPI0718120A2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2665736A1 (cg-RX-API-DMAC7.html) |
| EA (1) | EA200900593A1 (cg-RX-API-DMAC7.html) |
| IL (1) | IL198082A0 (cg-RX-API-DMAC7.html) |
| MX (1) | MX2009004244A (cg-RX-API-DMAC7.html) |
| NZ (1) | NZ577153A (cg-RX-API-DMAC7.html) |
| WO (1) | WO2008050096A1 (cg-RX-API-DMAC7.html) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011026241A1 (en) * | 2009-09-04 | 2011-03-10 | Zalicus Pharmaceuticals Ltd. | Substituted heterocyclic derivatives for the treatment of pain and epilepsy |
| US10208023B2 (en) | 2013-03-01 | 2019-02-19 | Mark G. DeGiacomo | Heterocyclic inhibitors of the sodium channel |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0619753D0 (en) | 2006-10-06 | 2006-11-15 | Chroma Therapeutics Ltd | Enzyme inhibitors |
| EA017198B1 (ru) * | 2006-10-30 | 2012-10-30 | Хрома Терапьютикс Лтд. | Гидроксаматы в качестве ингибиторов гистон-деацетилазы |
| US8129387B2 (en) | 2006-12-14 | 2012-03-06 | Vertex Pharmaceuticals Incorporated | Substituted 5,6-dihydroimidazo[1,5-F]pteridines useful as protein kinase inhibitors |
| GB0803747D0 (en) | 2008-02-29 | 2008-04-09 | Martin | Enzyme and receptor modulation |
| GB0807451D0 (en) * | 2008-04-24 | 2008-05-28 | Chroma Therapeutics Ltd | Inhibitors of PLK |
| JP5869338B2 (ja) | 2008-06-23 | 2016-02-24 | 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 | タンパク質キナーゼ阻害剤 |
| AU2009271663B2 (en) * | 2008-06-23 | 2014-04-17 | Vertex Pharmaceuticals Incorporated | Protein kinase inhibitors |
| GB0903480D0 (en) | 2009-02-27 | 2009-04-08 | Chroma Therapeutics Ltd | Enzyme Inhibitors |
| CN102020643A (zh) * | 2009-09-22 | 2011-04-20 | 上海恒瑞医药有限公司 | 二氢喋啶酮类衍生物、其制备方法及其在医药上的应用 |
| GB201211310D0 (en) | 2012-06-26 | 2012-08-08 | Chroma Therapeutics Ltd | CSF-1R kinase inhibitors |
| BR112015008167B1 (pt) | 2012-10-17 | 2020-11-17 | Macrophage Pharma Limited | composto, composição farmacêutica, métodos para a inibição da atividade de uma enzima quinase map p38, para o tratamento ou a prevenção de doença autoimune ou inflamatória em um indivíduo, e para o tratamento, a melhoria ou a redução da incidência de doença proliferativa de células em um indivíduo, uso de composto, e, ácido |
| US9566280B2 (en) | 2014-01-28 | 2017-02-14 | Massachusetts Institute Of Technology | Combination therapies and methods of use thereof for treating cancer |
| US10150756B2 (en) | 2014-01-31 | 2018-12-11 | Dana-Farber Cancer Institute, Inc. | Diaminopyrimidine benzenesulfone derivatives and uses thereof |
| WO2015117055A1 (en) * | 2014-01-31 | 2015-08-06 | Dana-Farber Cancer Institute, Inc. | Dihydropteridinone derivatives and uses thereof |
| EP3099693A4 (en) | 2014-01-31 | 2017-08-16 | Dana-Farber Cancer Institute, Inc. | Uses of diazepane derivatives |
| HK1256417A1 (zh) | 2015-09-11 | 2019-09-20 | 达纳-法伯癌症研究所股份有限公司 | 氰基噻吩並三唑並二氮雜環庚三烯及其用途 |
| SG11201803210YA (en) | 2015-11-25 | 2018-05-30 | Dana Farber Cancer Inst Inc | Bivalent bromodomain inhibitors and uses thereof |
| GB201713975D0 (en) | 2017-08-31 | 2017-10-18 | Macrophage Pharma Ltd | Medical use |
| US11773096B2 (en) | 2018-08-10 | 2023-10-03 | Yale University | Small-molecule PI5P4K alpha/beta inhibitors and methods of treatment using same |
| CN111039944B (zh) | 2018-10-12 | 2021-11-23 | 中国科学院合肥物质科学研究院 | Mst1激酶抑制剂及其用途 |
| KR102260995B1 (ko) * | 2018-11-28 | 2021-06-04 | 국립암센터 | Plk1의 활성 억제제를 유효성분으로 포함하는 암 예방 또는 치료용 약학적 조성물 |
| CN115947728B (zh) * | 2021-10-09 | 2024-01-09 | 沈阳药科大学 | 含磺酰基的二氢喋啶酮衍生物及其应用 |
| EP4479042A1 (en) | 2022-02-18 | 2024-12-25 | Massachusetts Institute Of Technology | Cancer treatment by combined inhibition of polo-like kinase and microtubule polymerization |
| CN118047779B (zh) * | 2022-11-09 | 2025-02-11 | 沈阳药科大学 | 含苯联杂芳基的二氢喋啶酮衍生物及其用途 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1632493A1 (de) * | 2004-08-25 | 2006-03-08 | Boehringer Ingelheim Pharma GmbH & Co.KG | Dihydropteridinonderivative, Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel |
| CA2575804A1 (en) * | 2004-08-26 | 2006-03-02 | Boehringer Ingelheim International Gmbh | Pteridinones used as plk (polo like kinase) inhibitors |
| CA2578560A1 (en) * | 2004-08-27 | 2006-03-02 | Boehringer Ingelheim International Gmbh | Dihydropteridinones, method for the production thereof, and use thereof as a medicament |
-
2007
- 2007-10-19 MX MX2009004244A patent/MX2009004244A/es not_active Application Discontinuation
- 2007-10-19 AU AU2007310604A patent/AU2007310604B2/en not_active Ceased
- 2007-10-19 WO PCT/GB2007/003998 patent/WO2008050096A1/en not_active Ceased
- 2007-10-19 AT AT07824247T patent/ATE542820T1/de active
- 2007-10-19 KR KR1020097010620A patent/KR20090071668A/ko not_active Withdrawn
- 2007-10-19 EA EA200900593A patent/EA200900593A1/ru unknown
- 2007-10-19 NZ NZ577153A patent/NZ577153A/en not_active IP Right Cessation
- 2007-10-19 BR BRPI0718120-5A patent/BRPI0718120A2/pt not_active IP Right Cessation
- 2007-10-19 EP EP07824247A patent/EP2079743B1/en not_active Not-in-force
- 2007-10-19 CA CA002665736A patent/CA2665736A1/en not_active Abandoned
- 2007-10-19 US US12/446,008 patent/US20100216802A1/en not_active Abandoned
- 2007-10-19 JP JP2009533934A patent/JP2010507639A/ja not_active Withdrawn
-
2009
- 2009-04-07 IL IL198082A patent/IL198082A0/en unknown
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011026241A1 (en) * | 2009-09-04 | 2011-03-10 | Zalicus Pharmaceuticals Ltd. | Substituted heterocyclic derivatives for the treatment of pain and epilepsy |
| US10208023B2 (en) | 2013-03-01 | 2019-02-19 | Mark G. DeGiacomo | Heterocyclic inhibitors of the sodium channel |
Also Published As
| Publication number | Publication date |
|---|---|
| EP2079743A1 (en) | 2009-07-22 |
| AU2007310604A1 (en) | 2008-05-02 |
| AU2007310604B2 (en) | 2012-02-02 |
| NZ577153A (en) | 2012-02-24 |
| ATE542820T1 (de) | 2012-02-15 |
| IL198082A0 (en) | 2009-12-24 |
| JP2010507639A (ja) | 2010-03-11 |
| US20100216802A1 (en) | 2010-08-26 |
| MX2009004244A (es) | 2009-05-14 |
| EA200900593A1 (ru) | 2010-06-30 |
| KR20090071668A (ko) | 2009-07-01 |
| WO2008050096A1 (en) | 2008-05-02 |
| EP2079743B1 (en) | 2012-01-25 |
| BRPI0718120A2 (pt) | 2013-11-12 |
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Legal Events
| Date | Code | Title | Description |
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| FZDE | Discontinued |
Effective date: 20131021 |