AU2007310604B2 - 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
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- AU2007310604B2 AU2007310604B2 AU2007310604A AU2007310604A AU2007310604B2 AU 2007310604 B2 AU2007310604 B2 AU 2007310604B2 AU 2007310604 A AU2007310604 A AU 2007310604A AU 2007310604 A AU2007310604 A AU 2007310604A AU 2007310604 B2 AU2007310604 B2 AU 2007310604B2
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- Prior art keywords
- amino
- cyclopentyl
- ethyl
- methyl
- oxo
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- 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
- 150000001875 compounds Chemical class 0.000 claims abstract description 80
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 75
- 239000001257 hydrogen Substances 0.000 claims abstract description 56
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 46
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 33
- 125000006413 ring segment Chemical group 0.000 claims abstract description 17
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 15
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 13
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 10
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 10
- 201000010099 disease Diseases 0.000 claims abstract description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 8
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 8
- 230000002062 proliferating effect Effects 0.000 claims abstract description 7
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 4
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 4
- 150000002367 halogens Chemical group 0.000 claims abstract description 4
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 3
- -1 4-{[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-5,6,7,8-tetrahydro pteridin-2-yl]amino}-3-methoxybenzoyl Chemical group 0.000 claims description 111
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 90
- 238000000034 method Methods 0.000 claims description 82
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 57
- 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 32
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
- 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
- 230000000694 effects Effects 0.000 claims description 20
- 108010056274 polo-like kinase 1 Proteins 0.000 claims description 20
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 125000002950 monocyclic group Chemical group 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 13
- 125000001424 substituent group Chemical group 0.000 claims description 13
- 108010051152 Carboxylesterase Proteins 0.000 claims description 11
- 102000013392 Carboxylesterase Human genes 0.000 claims description 11
- 230000003834 intracellular effect Effects 0.000 claims description 11
- 229910052799 carbon Inorganic materials 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
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 9
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 9
- 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 9
- 125000001153 fluoro group Chemical group F* 0.000 claims description 9
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 8
- 230000005764 inhibitory process Effects 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- 239000012453 solvate Substances 0.000 claims description 7
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- 150000001204 N-oxides Chemical class 0.000 claims description 6
- 125000002527 bicyclic carbocyclic group Chemical group 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 125000004185 ester group Chemical group 0.000 claims description 6
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- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims description 4
- 101150065749 Churc1 gene Proteins 0.000 claims description 4
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- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 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 4
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 3
- 125000001246 bromo group Chemical group Br* 0.000 claims description 3
- 125000002837 carbocyclic group Chemical group 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 238000001727 in vivo Methods 0.000 claims description 3
- 230000001404 mediated effect Effects 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
- 125000003277 amino group Chemical group 0.000 claims description 2
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 150000004677 hydrates Chemical class 0.000 claims description 2
- 238000000338 in vitro Methods 0.000 claims description 2
- 150000002825 nitriles Chemical class 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 2
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 1
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- 101100490437 Mus musculus Acvrl1 gene Proteins 0.000 claims 1
- 125000002947 alkylene group Chemical group 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
- 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
- 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
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- UAJUXJSXCLUTNU-UHFFFAOYSA-N pranlukast Chemical compound C=1C=C(OCCCCC=2C=CC=CC=2)C=CC=1C(=O)NC(C=1)=CC=C(C(C=2)=O)C=1OC=2C=1N=NNN=1 UAJUXJSXCLUTNU-UHFFFAOYSA-N 0.000 description 1
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- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical class N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 238000010517 secondary reaction Methods 0.000 description 1
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- 238000000926 separation method Methods 0.000 description 1
- 108010017797 serum-inducible kinase Proteins 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000004296 sodium metabisulphite Substances 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 239000012418 sodium perborate tetrahydrate Substances 0.000 description 1
- 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
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 230000020347 spindle assembly Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 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
- WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000002278 tabletting lubricant Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 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
- 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
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical group [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003554 tetrahydropyrrolyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 229950009811 ubenimex Drugs 0.000 description 1
- 230000014848 ubiquitin-dependent protein catabolic process Effects 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 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
- 239000000080 wetting agent Substances 0.000 description 1
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)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (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 |
| GB0715614A GB0715614D0 (en) | 2007-08-10 | 2007-08-10 | Inhibitors of plk |
| GB0715614.4 | 2007-08-10 | ||
| 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 (2)
| Publication Number | Publication Date |
|---|---|
| AU2007310604A1 AU2007310604A1 (en) | 2008-05-02 |
| AU2007310604B2 true AU2007310604B2 (en) | 2012-02-02 |
Family
ID=38896021
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2007310604A Ceased AU2007310604B2 (en) | 2006-10-25 | 2007-10-19 | Pteridine derivatives as polo-like kinase inhibitors useful in the treatment of cancer |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US20100216802A1 (enExample) |
| EP (1) | EP2079743B1 (enExample) |
| JP (1) | JP2010507639A (enExample) |
| KR (1) | KR20090071668A (enExample) |
| AT (1) | ATE542820T1 (enExample) |
| AU (1) | AU2007310604B2 (enExample) |
| BR (1) | BRPI0718120A2 (enExample) |
| CA (1) | CA2665736A1 (enExample) |
| EA (1) | EA200900593A1 (enExample) |
| IL (1) | IL198082A0 (enExample) |
| MX (1) | MX2009004244A (enExample) |
| NZ (1) | NZ577153A (enExample) |
| WO (1) | WO2008050096A1 (enExample) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0619753D0 (en) | 2006-10-06 | 2006-11-15 | Chroma Therapeutics Ltd | Enzyme inhibitors |
| MX2009004279A (es) * | 2006-10-30 | 2009-05-22 | Chroma Therapeutics Ltd | Hidroxamatos como inhibidores de histona desacetilasa. |
| CA2672612A1 (en) | 2006-12-14 | 2008-06-26 | Vertex Pharmaceuticals Incorporated | Compounds 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 |
| AU2009271663B2 (en) * | 2008-06-23 | 2014-04-17 | Vertex Pharmaceuticals Incorporated | Protein kinase inhibitors |
| EP2356122B1 (en) | 2008-06-23 | 2019-03-20 | Vertex Pharmaceuticals Incorporated | Protein kinase inhibitors |
| GB0903480D0 (en) | 2009-02-27 | 2009-04-08 | Chroma Therapeutics Ltd | Enzyme Inhibitors |
| US20120220603A1 (en) * | 2009-09-04 | 2012-08-30 | Zalicus Pharmaceuticals Ltd. | Substituted heterocyclic derivatives for the treatment of pain and epilepsy |
| 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 |
| SI2909175T1 (sl) | 2012-10-17 | 2017-08-31 | Macrophage Pharma Limited | Terc-butil-n-(2-(4-(6-amino-5-(2,4-difluorobenzoil)-2-oksopiridin-1 (2h)-il)-3,5-difluorofenil)etil)-l-alaninat ali njegova sol, hidrat ali solvat |
| US10208023B2 (en) | 2013-03-01 | 2019-02-19 | Mark G. DeGiacomo | Heterocyclic inhibitors of the sodium channel |
| US9566280B2 (en) | 2014-01-28 | 2017-02-14 | Massachusetts Institute Of Technology | Combination therapies and methods of use thereof for treating cancer |
| US20160347750A1 (en) * | 2014-01-31 | 2016-12-01 | Dana-Farber Cancer Institute, Inc. | Dihydropteridinone derivatives and uses thereof |
| 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 |
| KR20160115953A (ko) | 2014-01-31 | 2016-10-06 | 다나-파버 캔서 인스티튜트 인크. | 디아미노피리미딘 벤젠술폰 유도체 및 그의 용도 |
| 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 |
| GB201713975D0 (en) | 2017-08-31 | 2017-10-18 | Macrophage Pharma Ltd | Medical use |
| EP3833353A4 (en) * | 2018-08-10 | 2022-08-24 | 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 |
| WO2023158514A1 (en) | 2022-02-18 | 2023-08-24 | 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 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060046990A1 (en) * | 2004-08-27 | 2006-03-02 | Boehringer Ingelheim International Gmbh | New dihydropteridinones, processes for preparing them and their use as pharmaceutical compositions |
Family Cites Families (2)
| 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 |
| WO2006021547A1 (de) * | 2004-08-26 | 2006-03-02 | Boehringer Ingelheim International Gmbh | Pteridinone als plk (polo like kinase) inhibitoren |
-
2007
- 2007-10-19 EP EP07824247A patent/EP2079743B1/en not_active Not-in-force
- 2007-10-19 NZ NZ577153A patent/NZ577153A/en not_active IP Right Cessation
- 2007-10-19 CA CA002665736A patent/CA2665736A1/en not_active Abandoned
- 2007-10-19 EA EA200900593A patent/EA200900593A1/ru unknown
- 2007-10-19 AU AU2007310604A patent/AU2007310604B2/en not_active Ceased
- 2007-10-19 KR KR1020097010620A patent/KR20090071668A/ko not_active Withdrawn
- 2007-10-19 US US12/446,008 patent/US20100216802A1/en not_active Abandoned
- 2007-10-19 WO PCT/GB2007/003998 patent/WO2008050096A1/en not_active Ceased
- 2007-10-19 MX MX2009004244A patent/MX2009004244A/es not_active Application Discontinuation
- 2007-10-19 JP JP2009533934A patent/JP2010507639A/ja not_active Withdrawn
- 2007-10-19 AT AT07824247T patent/ATE542820T1/de active
- 2007-10-19 BR BRPI0718120-5A patent/BRPI0718120A2/pt not_active IP Right Cessation
-
2009
- 2009-04-07 IL IL198082A patent/IL198082A0/en unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060046990A1 (en) * | 2004-08-27 | 2006-03-02 | Boehringer Ingelheim International Gmbh | New dihydropteridinones, processes for preparing them and their use as pharmaceutical compositions |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2665736A1 (en) | 2008-05-02 |
| WO2008050096A1 (en) | 2008-05-02 |
| MX2009004244A (es) | 2009-05-14 |
| KR20090071668A (ko) | 2009-07-01 |
| AU2007310604A1 (en) | 2008-05-02 |
| IL198082A0 (en) | 2009-12-24 |
| JP2010507639A (ja) | 2010-03-11 |
| NZ577153A (en) | 2012-02-24 |
| BRPI0718120A2 (pt) | 2013-11-12 |
| EP2079743A1 (en) | 2009-07-22 |
| EA200900593A1 (ru) | 2010-06-30 |
| US20100216802A1 (en) | 2010-08-26 |
| ATE542820T1 (de) | 2012-02-15 |
| EP2079743B1 (en) | 2012-01-25 |
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