JP2007501774A - スタウロスポリンを含む組み合わせ - Google Patents
スタウロスポリンを含む組み合わせ Download PDFInfo
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- JP2007501774A JP2007501774A JP2006522329A JP2006522329A JP2007501774A JP 2007501774 A JP2007501774 A JP 2007501774A JP 2006522329 A JP2006522329 A JP 2006522329A JP 2006522329 A JP2006522329 A JP 2006522329A JP 2007501774 A JP2007501774 A JP 2007501774A
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- Prior art keywords
- alkyl
- aryl
- amino
- methyl
- phenyl
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- HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@H](NC)[C@@H](OC)[C@]4(C)O1 HKSZLNNOFSGOKW-FYTWVXJKSA-N 0.000 title claims description 12
- HKSZLNNOFSGOKW-UHFFFAOYSA-N ent-staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 HKSZLNNOFSGOKW-UHFFFAOYSA-N 0.000 title description 2
- CGPUWJWCVCFERF-UHFFFAOYSA-N staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(OC)O1 CGPUWJWCVCFERF-UHFFFAOYSA-N 0.000 title description 2
- 102100020718 Receptor-type tyrosine-protein kinase FLT3 Human genes 0.000 claims abstract description 74
- 101710151245 Receptor-type tyrosine-protein kinase FLT3 Proteins 0.000 claims abstract description 74
- FSPQCTGGIANIJZ-UHFFFAOYSA-N 2-[[(3,4-dimethoxyphenyl)-oxomethyl]amino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NC1=C(C(N)=O)C(CCCC2)=C2S1 FSPQCTGGIANIJZ-UHFFFAOYSA-N 0.000 claims abstract description 72
- 229940121372 histone deacetylase inhibitor Drugs 0.000 claims abstract description 52
- 239000003276 histone deacetylase inhibitor Substances 0.000 claims abstract description 52
- 238000011282 treatment Methods 0.000 claims abstract description 32
- 208000032839 leukemia Diseases 0.000 claims abstract description 15
- 206010025323 Lymphomas Diseases 0.000 claims abstract description 12
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 12
- 201000003793 Myelodysplastic syndrome Diseases 0.000 claims abstract description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
- 239000003814 drug Substances 0.000 claims abstract description 6
- 238000004519 manufacturing process Methods 0.000 claims abstract description 5
- -1 hydroxy, amino Chemical group 0.000 claims description 470
- 125000000217 alkyl group Chemical group 0.000 claims description 167
- 125000003118 aryl group Chemical group 0.000 claims description 130
- 229910052739 hydrogen Inorganic materials 0.000 claims description 85
- 150000001875 compounds Chemical class 0.000 claims description 82
- 229910052757 nitrogen Inorganic materials 0.000 claims description 77
- 229910052799 carbon Inorganic materials 0.000 claims description 65
- 150000003839 salts Chemical class 0.000 claims description 61
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 54
- 125000004432 carbon atom Chemical group C* 0.000 claims description 52
- 125000001072 heteroaryl group Chemical group 0.000 claims description 51
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 46
- 239000001257 hydrogen Substances 0.000 claims description 44
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 43
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 39
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 38
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 38
- 125000002252 acyl group Chemical group 0.000 claims description 36
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 36
- 125000003545 alkoxy group Chemical group 0.000 claims description 32
- 229910052717 sulfur Inorganic materials 0.000 claims description 32
- 229910052760 oxygen Inorganic materials 0.000 claims description 30
- BWDQBBCUWLSASG-MDZDMXLPSA-N (e)-n-hydroxy-3-[4-[[2-hydroxyethyl-[2-(1h-indol-3-yl)ethyl]amino]methyl]phenyl]prop-2-enamide Chemical group C=1NC2=CC=CC=C2C=1CCN(CCO)CC1=CC=C(\C=C\C(=O)NO)C=C1 BWDQBBCUWLSASG-MDZDMXLPSA-N 0.000 claims description 29
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 29
- 239000003112 inhibitor Substances 0.000 claims description 28
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 27
- 125000005037 alkyl phenyl group Chemical group 0.000 claims description 27
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 25
- 125000005842 heteroatom Chemical group 0.000 claims description 25
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
- 125000005843 halogen group Chemical group 0.000 claims description 22
- 150000002431 hydrogen Chemical class 0.000 claims description 21
- 239000001301 oxygen Substances 0.000 claims description 21
- 206010009944 Colon cancer Diseases 0.000 claims description 20
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 20
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 20
- 125000000623 heterocyclic group Chemical group 0.000 claims description 20
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 20
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 20
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 19
- 238000000034 method Methods 0.000 claims description 19
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 150000002367 halogens Chemical class 0.000 claims description 16
- 125000000266 alpha-aminoacyl group Chemical group 0.000 claims description 15
- 125000003277 amino group Chemical group 0.000 claims description 15
- 125000004122 cyclic group Chemical group 0.000 claims description 15
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 14
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 13
- 125000001931 aliphatic group Chemical group 0.000 claims description 11
- 125000005036 alkoxyphenyl group Chemical group 0.000 claims description 11
- 125000002837 carbocyclic group Chemical group 0.000 claims description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 9
- 239000000651 prodrug Substances 0.000 claims description 9
- 229940002612 prodrug Drugs 0.000 claims description 9
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 8
- 150000001721 carbon Chemical group 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 7
- ZLUZDKXBTNQWOL-MDZDMXLPSA-N (e)-n-hydroxy-3-[4-[[2-(1h-indol-3-yl)ethylamino]methyl]phenyl]prop-2-enamide Chemical compound C1=CC(/C=C/C(=O)NO)=CC=C1CNCCC1=CNC2=CC=CC=C12 ZLUZDKXBTNQWOL-MDZDMXLPSA-N 0.000 claims description 5
- 125000003367 polycyclic group Chemical group 0.000 claims description 5
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 4
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 4
- FPOHNWQLNRZRFC-ZHACJKMWSA-N panobinostat Chemical compound CC=1NC2=CC=CC=C2C=1CCNCC1=CC=C(\C=C\C(=O)NO)C=C1 FPOHNWQLNRZRFC-ZHACJKMWSA-N 0.000 claims description 4
- 125000004442 acylamino group Chemical group 0.000 claims description 3
- 125000004532 benzofuran-3-yl group Chemical group O1C=C(C2=C1C=CC=C2)* 0.000 claims description 3
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 claims description 3
- 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000004585 polycyclic heterocycle group Chemical group 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 229940043355 kinase inhibitor Drugs 0.000 abstract description 15
- 239000003757 phosphotransferase inhibitor Substances 0.000 abstract description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 9
- 201000010099 disease Diseases 0.000 abstract description 8
- 201000011510 cancer Diseases 0.000 abstract description 4
- 125000001424 substituent group Chemical group 0.000 description 66
- 210000004027 cell Anatomy 0.000 description 60
- 150000003254 radicals Chemical class 0.000 description 43
- 125000003282 alkyl amino group Chemical group 0.000 description 30
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 27
- BMGQWWVMWDBQGC-IIFHNQTCSA-N midostaurin Chemical compound CN([C@H]1[C@H]([C@]2(C)O[C@@H](N3C4=CC=CC=C4C4=C5C(=O)NCC5=C5C6=CC=CC=C6N2C5=C43)C1)OC)C(=O)C1=CC=CC=C1 BMGQWWVMWDBQGC-IIFHNQTCSA-N 0.000 description 22
- 229950010895 midostaurin Drugs 0.000 description 22
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 21
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 16
- 239000000203 mixture Substances 0.000 description 16
- 229920006395 saturated elastomer Polymers 0.000 description 15
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 14
- 230000000694 effects Effects 0.000 description 14
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 14
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 13
- 125000004433 nitrogen atom Chemical group N* 0.000 description 13
- 239000011593 sulfur Substances 0.000 description 13
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 11
- 125000003342 alkenyl group Chemical group 0.000 description 11
- 125000001183 hydrocarbyl group Chemical group 0.000 description 11
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 10
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 10
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 10
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 10
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 10
- 239000002953 phosphate buffered saline Substances 0.000 description 10
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 125000004414 alkyl thio group Chemical group 0.000 description 9
- 230000006907 apoptotic process Effects 0.000 description 9
- 125000002619 bicyclic group Chemical group 0.000 description 9
- 238000000684 flow cytometry Methods 0.000 description 9
- 125000004076 pyridyl group Chemical group 0.000 description 9
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
- 125000004423 acyloxy group Chemical group 0.000 description 8
- 125000004103 aminoalkyl group Chemical group 0.000 description 8
- 150000005840 aryl radicals Chemical class 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 8
- 125000001624 naphthyl group Chemical group 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
- 125000001544 thienyl group Chemical group 0.000 description 8
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 7
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 7
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 7
- 125000002015 acyclic group Chemical group 0.000 description 7
- 125000005115 alkyl carbamoyl group Chemical group 0.000 description 7
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 7
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 7
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 7
- 229910052801 chlorine Inorganic materials 0.000 description 7
- 229910052731 fluorine Inorganic materials 0.000 description 7
- 239000011737 fluorine Substances 0.000 description 7
- 125000002541 furyl group Chemical group 0.000 description 7
- 125000005956 isoquinolyl group Chemical group 0.000 description 7
- 125000000842 isoxazolyl group Chemical group 0.000 description 7
- 125000002950 monocyclic group Chemical group 0.000 description 7
- 125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 description 7
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 7
- 125000005429 oxyalkyl group Chemical group 0.000 description 7
- 125000005493 quinolyl group Chemical group 0.000 description 7
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 6
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 6
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 description 6
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 6
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 6
- 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 description 6
- 125000002883 imidazolyl group Chemical group 0.000 description 6
- 125000001041 indolyl group Chemical group 0.000 description 6
- 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 6
- 125000002971 oxazolyl group Chemical group 0.000 description 6
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 6
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 description 6
- 125000000168 pyrrolyl group Chemical group 0.000 description 6
- 125000000335 thiazolyl group Chemical group 0.000 description 6
- 125000004487 4-tetrahydropyranyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 5
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 5
- 230000000903 blocking effect Effects 0.000 description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 230000022131 cell cycle Effects 0.000 description 5
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 5
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 4
- 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 description 4
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 4
- 239000004215 Carbon black (E152) Substances 0.000 description 4
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 4
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 4
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 125000005236 alkanoylamino group Chemical group 0.000 description 4
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 4
- 230000001640 apoptogenic effect Effects 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 4
- 231100000673 dose–response relationship Toxicity 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 229930195733 hydrocarbon Natural products 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 4
- 235000011007 phosphoric acid Nutrition 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 238000001262 western blot Methods 0.000 description 4
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 3
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 3
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 3
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 3
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 3
- PBCZSGKMGDDXIJ-HQCWYSJUSA-N 7-hydroxystaurosporine Chemical compound N([C@H](O)C1=C2C3=CC=CC=C3N3C2=C24)C(=O)C1=C2C1=CC=CC=C1N4[C@H]1C[C@@H](NC)[C@@H](OC)[C@]3(C)O1 PBCZSGKMGDDXIJ-HQCWYSJUSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
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- 0 CC([C@@]([C@](C1C=O)O)O)O[C@]1(C)C=* Chemical compound CC([C@@]([C@](C1C=O)O)O)O[C@]1(C)C=* 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 3
- 230000004568 DNA-binding Effects 0.000 description 3
- 101100016370 Danio rerio hsp90a.1 gene Proteins 0.000 description 3
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- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 102000004140 Oncostatin M Human genes 0.000 description 3
- 108090000630 Oncostatin M Proteins 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
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- 101100071627 Schizosaccharomyces pombe (strain 972 / ATCC 24843) swo1 gene Proteins 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical group [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 125000005138 alkoxysulfonyl group Chemical group 0.000 description 3
- 125000005530 alkylenedioxy group Chemical group 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000007962 solid dispersion Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229950000244 sulfanilic acid Drugs 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000006633 tert-butoxycarbonylamino group Chemical group 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
- A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/553—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- 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
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Physical Education & Sports Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US49382803P | 2003-08-08 | 2003-08-08 | |
| PCT/EP2004/008848 WO2005014004A1 (en) | 2003-08-08 | 2004-08-06 | Combinations comprising staurosporines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007501774A true JP2007501774A (ja) | 2007-02-01 |
| JP2007501774A5 JP2007501774A5 (https=) | 2007-11-01 |
Family
ID=34135288
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006522329A Pending JP2007501774A (ja) | 2003-08-08 | 2004-08-06 | スタウロスポリンを含む組み合わせ |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US20070191338A1 (https=) |
| EP (2) | EP1653973A1 (https=) |
| JP (1) | JP2007501774A (https=) |
| CN (1) | CN100536850C (https=) |
| AU (1) | AU2004262927B2 (https=) |
| BR (1) | BRPI0413439A (https=) |
| CA (1) | CA2533861A1 (https=) |
| MX (1) | MXPA06001524A (https=) |
| WO (1) | WO2005014004A1 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015527316A (ja) * | 2012-07-13 | 2015-09-17 | トゥルン イリオピスト | 併用療法ｉｉｉ |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7154002B1 (en) | 2002-10-08 | 2006-12-26 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
| CA2518318A1 (en) | 2003-03-17 | 2004-09-30 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
| GB0419159D0 (en) * | 2004-08-27 | 2004-09-29 | Novartis Ag | Organic compounds |
| JP2008524246A (ja) | 2004-12-16 | 2008-07-10 | タケダ サン ディエゴ インコーポレイテッド | ヒストンデアセチラーゼ阻害剤 |
| US7642253B2 (en) | 2005-05-11 | 2010-01-05 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
| EA200800321A1 (ru) | 2005-07-14 | 2008-06-30 | Такеда Сан Диего, Инк. | Ингибиторы гистондеацетилазы |
| CN101237873A (zh) * | 2005-08-09 | 2008-08-06 | 美因茨约翰内斯古滕贝格大学 | 用于治疗非小细胞肺癌的星形孢菌素衍生物 |
| WO2007030455A2 (en) * | 2005-09-07 | 2007-03-15 | Novartis Ag | Mutations and polymorphisms of hdac10 |
| GB0522932D0 (en) * | 2005-11-10 | 2005-12-21 | Univ Southampton | PKC412 in treatment of atypical chronic myeloid leukemia |
| GB0612542D0 (en) * | 2006-06-23 | 2006-08-02 | Novartis Ag | Combinations comprising staurosporines |
| NZ588069A (en) | 2008-03-26 | 2012-06-29 | Novartis Ag | Hydroxamate-based inhibitors of deacetylases b |
| US20110053925A1 (en) * | 2009-08-28 | 2011-03-03 | Novartis Ag | Hydroxamate-Based Inhibitors of Deacetylases |
| CN102101866A (zh) * | 2010-11-04 | 2011-06-22 | 中国海洋大学 | 十字孢碱卤代衍生物及其制备方法和应用 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002022577A2 (en) * | 2000-09-01 | 2002-03-21 | Novartis Ag | Hydroxamate derivatives useful as deacetylase inhibitors |
| JP2006528952A (ja) * | 2003-05-21 | 2006-12-28 | ノバルティス アクチエンゲゼルシャフト | ヒストンデアセチラーゼ阻害剤と化学療法剤の組み合わせ |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62220196A (ja) | 1986-03-20 | 1987-09-28 | Kyowa Hakko Kogyo Co Ltd | 新規物質ｕｃｎ―０１ |
| IL86632A0 (en) | 1987-06-15 | 1988-11-30 | Ciba Geigy Ag | Derivatives substituted at methyl-amino nitrogen |
| US5093330A (en) | 1987-06-15 | 1992-03-03 | Ciba-Geigy Corporation | Staurosporine derivatives substituted at methylamino nitrogen |
| CZ280738B6 (cs) | 1988-02-10 | 1996-04-17 | F. Hoffmann - La Roche And Co., Aktiengesellschaft | Substituované pyrroly, jejich použití pro výrobu léčiv a léčiva na jejich bázi |
| GB8803048D0 (en) | 1988-02-10 | 1988-03-09 | Hoffmann La Roche | Substituted pyrroles |
| MC2096A1 (fr) | 1989-02-23 | 1991-02-15 | Hoffmann La Roche | Pyrroles substitues |
| CA2046801C (en) | 1990-08-07 | 2002-02-26 | Peter D. Davis | Substituted pyrroles |
| WO1993007153A1 (en) | 1991-10-10 | 1993-04-15 | Schering Corporation | 4'-(n-substituted-n-oxide)staurosporine derivatives |
| DE69326388T2 (de) | 1992-06-22 | 1999-12-30 | Kyowa Hakko Kogyo Co., Ltd. | Verfahren zur Herstellung von Staurosporin-Derivaten |
| US5461146A (en) | 1992-07-24 | 1995-10-24 | Cephalon, Inc. | Selected protein kinase inhibitors for the treatment of neurological disorders |
| PH30300A (en) | 1993-05-07 | 1997-01-20 | Ciba Geigy Ag | Polycyclic compounds and processes for the preparation thereof |
| AU678435B2 (en) | 1993-05-10 | 1997-05-29 | F. Hoffmann-La Roche Ag | Substituted pyrroles |
| NO308798B1 (no) | 1993-12-07 | 2000-10-30 | Lilly Co Eli | Proteinkinase-C-hemmere, anvendelse av samme for fremstilling av farmasøytika samt farmasøytisk formulering omfattende samme |
| GB9325395D0 (en) | 1993-12-11 | 1994-02-16 | Ciba Geigy Ag | Compositions |
| AU2565795A (en) | 1994-06-01 | 1995-12-21 | Ciba-Geigy Ag | Carbazole derivatives as agents against multi-drug resistance |
| EP0763042A1 (en) | 1994-06-01 | 1997-03-19 | Novartis AG | Polycyclic lactam derivatives for sensitizing multidrug-resistant cells to antitumour agents |
| EP0711557A1 (de) | 1994-11-09 | 1996-05-15 | Ciba-Geigy Ag | Pharmazeutische Formulierungsgrundlage |
| EP0733358A3 (de) | 1995-03-21 | 1998-05-20 | Novartis AG | Intravenös applizierbare Nanosuspensionen |
| NL1003692C2 (nl) | 1996-07-26 | 1998-01-28 | Stork Protecon Langen Bv | Inrichting voor het afscheiden van vleesmassa van van vleesresten voorziene botten. |
| CO4940430A1 (es) | 1997-07-07 | 2000-07-24 | Novartis Ag | Compuestos policiclicos que contienen estaurosporina hidrogenada con propiedades farmacologicas convenientes y un efecto inhibidor sobre el crecimiento de las celulas tumorales |
| DE19744676A1 (de) * | 1997-10-10 | 1999-04-15 | Forschungszentrum Borstel Zent | Kombinationspräparate für die Therapie von Tumoren |
| AR035885A1 (es) * | 2001-05-14 | 2004-07-21 | Novartis Ag | Derivados de 4-amino-5-fenil-7-ciclobutilpirrolo (2,3-d)pirimidina, un proceso para su preparacion, una composicion farmaceutica y el uso de dichos derivados para la preparacion de una composicion farmaceutica |
| ES2269793T3 (es) * | 2001-10-30 | 2007-04-01 | Novartis Ag | Derivados de estaurospina como inhibidores de la actividad de tirosina quinasa receptora flt3. |
| US20040152632A1 (en) * | 2002-11-06 | 2004-08-05 | Wyeth | Combination therapy for the treatment of acute leukemia and myelodysplastic syndrome |
| SI1611088T1 (sl) * | 2003-04-07 | 2009-12-31 | Pharmacyclics Inc | Hidroksamati kot terapevtska sredstva |
-
2004
- 2004-08-06 BR BRPI0413439-7A patent/BRPI0413439A/pt not_active IP Right Cessation
- 2004-08-06 AU AU2004262927A patent/AU2004262927B2/en not_active Ceased
- 2004-08-06 JP JP2006522329A patent/JP2007501774A/ja active Pending
- 2004-08-06 MX MXPA06001524A patent/MXPA06001524A/es not_active Application Discontinuation
- 2004-08-06 EP EP04763879A patent/EP1653973A1/en not_active Withdrawn
- 2004-08-06 US US10/567,897 patent/US20070191338A1/en not_active Abandoned
- 2004-08-06 CA CA002533861A patent/CA2533861A1/en not_active Abandoned
- 2004-08-06 WO PCT/EP2004/008848 patent/WO2005014004A1/en not_active Ceased
- 2004-08-06 CN CNB2004800227221A patent/CN100536850C/zh not_active Expired - Fee Related
- 2004-08-06 EP EP10175357A patent/EP2305265A1/en not_active Withdrawn
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002022577A2 (en) * | 2000-09-01 | 2002-03-21 | Novartis Ag | Hydroxamate derivatives useful as deacetylase inhibitors |
| JP2006528952A (ja) * | 2003-05-21 | 2006-12-28 | ノバルティス アクチエンゲゼルシャフト | ヒストンデアセチラーゼ阻害剤と化学療法剤の組み合わせ |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015527316A (ja) * | 2012-07-13 | 2015-09-17 | トゥルン イリオピスト | 併用療法ｉｉｉ |
| US10166241B2 (en) | 2012-07-13 | 2019-01-01 | Turun Yliopisto | Combination Therapy III |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2005014004A1 (en) | 2005-02-17 |
| CN100536850C (zh) | 2009-09-09 |
| EP2305265A1 (en) | 2011-04-06 |
| US20070191338A1 (en) | 2007-08-16 |
| MXPA06001524A (es) | 2006-05-15 |
| CN1832747A (zh) | 2006-09-13 |
| EP1653973A1 (en) | 2006-05-10 |
| AU2004262927B2 (en) | 2008-05-22 |
| BRPI0413439A (pt) | 2006-10-17 |
| AU2004262927A1 (en) | 2005-02-17 |
| CA2533861A1 (en) | 2005-02-17 |
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