JP2005507412A5 - - Google Patents

Info

Publication number

JP2005507412A5

JP2005507412A5 JP2003539690A JP2003539690A JP2005507412A5 JP 2005507412 A5 JP2005507412 A5 JP 2005507412A5 JP 2003539690 A JP2003539690 A JP 2003539690A JP 2003539690 A JP2003539690 A JP 2003539690A JP 2005507412 A5 JP2005507412 A5 JP 2005507412A5

Authority

JP

Japan

Prior art keywords

hydrogen

formula

substituted

mono

acyl

Prior art date

2002-10-29

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.)

Granted

Links

• Espacenet
• Global Dossier
• Discuss

• -1 hydroxy, amino Chemical group 0.000 claims description 61
• 125000000217 alkyl group Chemical group 0.000 claims description 25
• 229910052739 hydrogen Inorganic materials 0.000 claims description 17
• 239000001257 hydrogen Substances 0.000 claims description 17
• 125000004432 carbon atom Chemical group C* 0.000 claims description 16
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
• 125000002252 acyl group Chemical group 0.000 claims description 13
• 125000001931 aliphatic group Chemical group 0.000 claims description 12
• 125000000623 heterocyclic group Chemical group 0.000 claims description 11
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
• 125000002837 carbocyclic group Chemical group 0.000 claims description 8
• 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 8
• 125000003545 alkoxy group Chemical group 0.000 claims description 7
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
• 229910052736 halogen Inorganic materials 0.000 claims description 7
• 150000002367 halogens Chemical class 0.000 claims description 7
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 6
• 150000003839 salts Chemical class 0.000 claims description 6
• 125000005842 heteroatom Chemical group 0.000 claims description 5
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
• 125000002883 imidazolyl group Chemical group 0.000 claims description 2
• 229910052760 oxygen Inorganic materials 0.000 claims description 2
• 239000001301 oxygen Substances 0.000 claims description 2
• 101000932478 Homo sapiens Receptor-type tyrosine-protein kinase FLT3 Proteins 0.000 claims 10
• 102100020718 Receptor-type tyrosine-protein kinase FLT3 Human genes 0.000 claims 10
• 230000000694 effects Effects 0.000 claims 10
• 238000000034 method Methods 0.000 claims 10
• 102000027426 receptor tyrosine kinases Human genes 0.000 claims 10
• 108091008598 receptor tyrosine kinases Proteins 0.000 claims 10
• 201000003793 Myelodysplastic syndrome Diseases 0.000 claims 8
• 201000010099 disease Diseases 0.000 claims 8
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 8
• 150000002431 hydrogen Chemical class 0.000 claims 8
• 230000009711 regulatory function Effects 0.000 claims 8
• 150000001875 compounds Chemical class 0.000 claims 6
• 208000031261 Acute myeloid leukaemia Diseases 0.000 claims 5
• 241000124008 Mammalia Species 0.000 claims 5
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims 5
• 125000005037 alkyl phenyl group Chemical group 0.000 claims 4
• 208000032839 leukemia Diseases 0.000 claims 4
• 238000004519 manufacturing process Methods 0.000 claims 4
• 239000008194 pharmaceutical composition Substances 0.000 claims 4
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 4
• 125000005036 alkoxyphenyl group Chemical group 0.000 claims 2
• 230000005764 inhibitory process Effects 0.000 claims 2
• 239000000463 material Substances 0.000 claims 2
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 2
• XXUNIGZDNWWYED-UHFFFAOYSA-N 2-methylbenzamide Chemical compound CC1=CC=CC=C1C(N)=O XXUNIGZDNWWYED-UHFFFAOYSA-N 0.000 claims 1
• 125000003277 amino group Chemical group 0.000 claims 1
• 239000003814 drug Substances 0.000 claims 1
• 229940079593 drug Drugs 0.000 claims 1
• IIQIEMHSDLLZQA-QZPVEUDVSA-N n-((9s,10r,11r,13r)-2,3,10,11,12,13-hexahydro-10-methoxy-9-methyl-1-oxo-9,13-epoxy-1h,9h-diindolo(1,2,3-gh:3',2',1'-lm)pyrrolo(3,4-j)(1,7)benzodiazonin-11-yl)-n-methyl-benzamide Chemical compound CN([C@H]1[C@@]([C@]2(C)O[C@H]1N1C3=CC=CC=C3C3=C4C(=O)NCC4=C4C5=CC=CC=C5N2C4=C31)(C)OC)C(=O)C1=CC=CC=C1 IIQIEMHSDLLZQA-QZPVEUDVSA-N 0.000 claims 1
• 239000005022 packaging material Substances 0.000 claims 1
• 239000000825 pharmaceutical preparation Substances 0.000 claims 1
• 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
• HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical class 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 claims 1
• 229910052757 nitrogen Inorganic materials 0.000 description 7
• 125000001424 substituent group Chemical group 0.000 description 7
• 125000001183 hydrocarbyl group Chemical group 0.000 description 5
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
• 125000003282 alkyl amino group Chemical group 0.000 description 3
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 3
• 125000000753 cycloalkyl group Chemical group 0.000 description 3
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• 125000004423 acyloxy group Chemical group 0.000 description 2
• 125000004471 alkyl aminosulfonyl group Chemical group 0.000 description 2
• 125000004414 alkyl thio group Chemical group 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
• 125000005843 halogen group Chemical group 0.000 description 2
• 239000011630 iodine Substances 0.000 description 2
• 229910052740 iodine Inorganic materials 0.000 description 2
• 125000002950 monocyclic group Chemical group 0.000 description 2
• 235000011007 phosphoric acid Nutrition 0.000 description 2
• 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
• 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
• 125000004487 4-tetrahydropyranyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• HXELGNKCCDGMMN-UHFFFAOYSA-N [F].[Cl] Chemical compound [F].[Cl] HXELGNKCCDGMMN-UHFFFAOYSA-N 0.000 description 1
• 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 description 1
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
• 125000005236 alkanoylamino group Chemical group 0.000 description 1
• 125000003342 alkenyl group Chemical group 0.000 description 1
• 125000005138 alkoxysulfonyl group Chemical group 0.000 description 1
• 125000005115 alkyl carbamoyl group Chemical group 0.000 description 1
• 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
• 125000005530 alkylenedioxy group Chemical group 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 125000003118 aryl group Chemical group 0.000 description 1
• 125000004429 atom Chemical group 0.000 description 1
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 description 1
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
• 125000002619 bicyclic group Chemical group 0.000 description 1
• 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
• 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• 239000000460 chlorine Substances 0.000 description 1
• 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 description 1
• 125000000392 cycloalkenyl group Chemical group 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 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 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• XPPKVPWEQAFLFU-UHFFFAOYSA-N diphosphoric acid Chemical compound OP(O)(=O)OP(O)(O)=O XPPKVPWEQAFLFU-UHFFFAOYSA-N 0.000 description 1
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 125000005956 isoquinolyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 125000000468 ketone group Chemical group 0.000 description 1
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
• 125000005322 morpholin-1-yl group Chemical group 0.000 description 1
• 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 description 1
• 125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 125000004043 oxo group Chemical group O=* 0.000 description 1
• 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
• 125000006239 protecting group Chemical group 0.000 description 1
• 125000004076 pyridyl group Chemical group 0.000 description 1
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• 125000005493 quinolyl group Chemical group 0.000 description 1
• 125000006413 ring segment Chemical group 0.000 description 1
• 229920006395 saturated elastomer Polymers 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
• 125000000547 substituted alkyl group Chemical group 0.000 description 1
• 239000011593 sulfur Chemical group 0.000 description 1
• 229910052717 sulfur Chemical group 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
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000001302 tertiary amino group Chemical group 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 229920002554 vinyl polymer Polymers 0.000 description 1