CA2729690A1 - Nouveaux pyrrolo [2,3-a] carbazoles et leur utilisation comme inhibiteurs des kinases pim - Google Patents
Nouveaux pyrrolo [2,3-a] carbazoles et leur utilisation comme inhibiteurs des kinases pim Download PDFInfo
- Publication number
- CA2729690A1 CA2729690A1 CA2729690A CA2729690A CA2729690A1 CA 2729690 A1 CA2729690 A1 CA 2729690A1 CA 2729690 A CA2729690 A CA 2729690A CA 2729690 A CA2729690 A CA 2729690A CA 2729690 A1 CA2729690 A1 CA 2729690A1
- Authority
- CA
- Canada
- Prior art keywords
- dihydropyrrolo
- carbazol
- substituted
- groups
- carbaldehyde
- 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
- QKYLZESNWDGRJB-UHFFFAOYSA-N pyrrolo[2,3-a]carbazole Chemical class C12=CC=CC=C2N=C2C1=CC=C1C=CN=C12 QKYLZESNWDGRJB-UHFFFAOYSA-N 0.000 title abstract description 5
- 229940043355 kinase inhibitor Drugs 0.000 title description 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 17
- 239000003112 inhibitor Substances 0.000 claims abstract description 10
- 150000001875 compounds Chemical class 0.000 claims description 152
- -1 sulfophenyl group Chemical group 0.000 claims description 54
- 239000000203 mixture Substances 0.000 claims description 53
- 125000005843 halogen group Chemical group 0.000 claims description 29
- 125000003118 aryl group Chemical group 0.000 claims description 27
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 25
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 22
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 22
- 229920006395 saturated elastomer Polymers 0.000 claims description 22
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 21
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 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 18
- 150000002825 nitriles Chemical class 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 15
- 101100297651 Mus musculus Pim2 gene Proteins 0.000 claims description 15
- 101001001642 Xenopus laevis Serine/threonine-protein kinase pim-3 Proteins 0.000 claims description 15
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 14
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 14
- 101100297652 Coturnix japonica PIM3 gene Proteins 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 125000001188 haloalkyl group Chemical group 0.000 claims description 13
- 230000000694 effects Effects 0.000 claims description 12
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 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 11
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 11
- WRBOHOGDAJPJOQ-UHFFFAOYSA-N 9H-Carbazole-3-carboxaldehyde Chemical compound C1=CC=C2C3=CC(C=O)=CC=C3NC2=C1 WRBOHOGDAJPJOQ-UHFFFAOYSA-N 0.000 claims description 10
- 239000002608 ionic liquid Substances 0.000 claims description 10
- 125000001153 fluoro group Chemical group F* 0.000 claims description 8
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 claims description 8
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical group NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 claims description 8
- 229940067157 phenylhydrazine Drugs 0.000 claims description 8
- 125000006728 (C1-C6) alkynyl group Chemical group 0.000 claims description 7
- 125000006582 (C5-C6) heterocycloalkyl group Chemical group 0.000 claims description 7
- PZBQSOWJBOUUIV-UHFFFAOYSA-N 6,8-dichloro-1,10-dihydropyrrolo[2,3-a]carbazole-3-carbaldehyde Chemical compound C=1C(Cl)=CC(Cl)=C2C=1NC1=C2C=CC2=C1NC=C2C=O PZBQSOWJBOUUIV-UHFFFAOYSA-N 0.000 claims description 7
- JRPUZUBQJFQSQO-UHFFFAOYSA-N 7-bromo-1,10-dihydropyrrolo[2,3-a]carbazole Chemical compound C12=CC(Br)=CC=C2NC2=C1C=CC1=C2NC=C1 JRPUZUBQJFQSQO-UHFFFAOYSA-N 0.000 claims description 7
- CMILZUZLXJQSGJ-UHFFFAOYSA-N 9-bromo-1,10-dihydropyrrolo[2,3-a]carbazole-3-carbaldehyde Chemical compound BrC1=CC=CC2=C1NC1=C2C=CC2=C1NC=C2C=O CMILZUZLXJQSGJ-UHFFFAOYSA-N 0.000 claims description 7
- ZRRGYYZOLYHGAW-UHFFFAOYSA-N 9-ethyl-1,10-dihydropyrrolo[2,3-a]carbazole-3-carbaldehyde Chemical compound CCC1=CC=CC2=C1NC1=C2C=CC2=C1NC=C2C=O ZRRGYYZOLYHGAW-UHFFFAOYSA-N 0.000 claims description 7
- VIRITAWLUCSUIP-UHFFFAOYSA-N 9-fluoro-1,10-dihydropyrrolo[2,3-a]carbazole-3-carbaldehyde Chemical compound FC1=CC=CC2=C1NC1=C2C=CC2=C1NC=C2C=O VIRITAWLUCSUIP-UHFFFAOYSA-N 0.000 claims description 7
- 125000001118 alkylidene group Chemical group 0.000 claims description 7
- 125000004104 aryloxy group Chemical group 0.000 claims description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 125000002950 monocyclic group Chemical group 0.000 claims description 7
- 239000001301 oxygen Substances 0.000 claims description 7
- 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims description 6
- IYKWFKKDLTZONH-UHFFFAOYSA-N 6-bromo-1,10-dihydropyrrolo[2,3-a]carbazole-3-carbaldehyde Chemical compound C1=2C(Br)=CC=CC=2NC2=C1C=CC1=C2NC=C1C=O IYKWFKKDLTZONH-UHFFFAOYSA-N 0.000 claims description 6
- BFWHRHJPPAUSLJ-UHFFFAOYSA-N 7-(2,4-difluorophenyl)-1,10-dihydropyrrolo[2,3-a]carbazole-3-carbaldehyde Chemical compound FC1=CC(F)=CC=C1C1=CC=C(NC=2C=3NC=C(C=O)C=3C=CC=22)C2=C1 BFWHRHJPPAUSLJ-UHFFFAOYSA-N 0.000 claims description 6
- MWJXEWYSFDLQRR-UHFFFAOYSA-N 7-fluoro-1,10-dihydropyrrolo[2,3-a]carbazole-3-carbaldehyde Chemical compound C12=CC(F)=CC=C2NC2=C1C=CC1=C2NC=C1C=O MWJXEWYSFDLQRR-UHFFFAOYSA-N 0.000 claims description 6
- OGEKUJPOQMHESI-UHFFFAOYSA-N 8-methyl-1,10-dihydropyrrolo[2,3-a]carbazole-3-carbaldehyde Chemical compound C=1C(C)=CC=C2C=1NC1=C2C=CC2=C1NC=C2C=O OGEKUJPOQMHESI-UHFFFAOYSA-N 0.000 claims description 6
- 125000004429 atom Chemical group 0.000 claims description 6
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
- 125000004122 cyclic group Chemical group 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- BPHGZSRGCZJRGO-UHFFFAOYSA-N 1,10-dihydropyrrolo[2,3-a]carbazole Chemical compound C1=CC=C2NC3=C(NC=C4)C4=CC=C3C2=C1 BPHGZSRGCZJRGO-UHFFFAOYSA-N 0.000 claims description 4
- VWNCOFUKBTYAON-UHFFFAOYSA-N 1,10-dihydropyrrolo[2,3-a]carbazole-3-carbaldehyde Chemical compound C12=CC=CC=C2NC2=C1C=CC1=C2NC=C1C=O VWNCOFUKBTYAON-UHFFFAOYSA-N 0.000 claims description 4
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 238000006919 indolization reaction Methods 0.000 claims description 4
- 230000003287 optical effect Effects 0.000 claims description 4
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 3
- KUIXBLRMWNOGNN-UHFFFAOYSA-N 7-bromo-1,10-dihydropyrrolo[2,3-a]carbazole-3-carbaldehyde Chemical compound C12=CC(Br)=CC=C2NC2=C1C=CC1=C2NC=C1C=O KUIXBLRMWNOGNN-UHFFFAOYSA-N 0.000 claims description 3
- MXUOJMMSWVSNGG-UHFFFAOYSA-N 7-phenyl-1,10-dihydropyrrolo[2,3-a]carbazole-3-carbaldehyde Chemical compound O=CC1=CNC(C=2NC3=CC=4)=C1C=CC=2C3=CC=4C1=CC=CC=C1 MXUOJMMSWVSNGG-UHFFFAOYSA-N 0.000 claims description 3
- 125000002619 bicyclic group Chemical group 0.000 claims description 3
- 150000003857 carboxamides Chemical group 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- VOSIZKZMNWMHTH-UHFFFAOYSA-N 1,10-dihydropyrrolo[2,3-a]carbazol-3-ylmethanol Chemical compound C12=CC=CC=C2NC2=C1C=CC1=C2NC=C1CO VOSIZKZMNWMHTH-UHFFFAOYSA-N 0.000 claims description 2
- SNKWXCJZGPJMHY-UHFFFAOYSA-N 1,10-dihydropyrrolo[2,3-a]carbazole-7-carbonitrile Chemical compound C12=CC(C#N)=CC=C2NC2=C1C=CC1=C2NC=C1 SNKWXCJZGPJMHY-UHFFFAOYSA-N 0.000 claims description 2
- IPZURMNMOLTFSU-UHFFFAOYSA-N 1-(1,10-dihydropyrrolo[2,3-a]carbazol-3-yl)-2,2,2-trifluoroethanone Chemical compound C12=CC=CC=C2NC2=C1C=CC1=C2NC=C1C(=O)C(F)(F)F IPZURMNMOLTFSU-UHFFFAOYSA-N 0.000 claims description 2
- SQTJPZLGERPVDT-UHFFFAOYSA-N 1-(benzenesulfonyl)-7-bromo-10h-pyrrolo[2,3-a]carbazole Chemical compound C12=CC(Br)=CC=C2NC(C2=3)=C1C=CC=3C=CN2S(=O)(=O)C1=CC=CC=C1 SQTJPZLGERPVDT-UHFFFAOYSA-N 0.000 claims description 2
- LKHSHKRKEPEPKU-UHFFFAOYSA-N 1-[4-(1,10-dihydropyrrolo[2,3-a]carbazol-7-yl)phenyl]ethanone Chemical compound C1=CC(C(=O)C)=CC=C1C1=CC=C(NC=2C=3NC=CC=3C=CC=22)C2=C1 LKHSHKRKEPEPKU-UHFFFAOYSA-N 0.000 claims description 2
- NOFRRBJDVTZROX-UHFFFAOYSA-N 2-(1,10-dihydropyrrolo[2,3-a]carbazol-3-yl)-n,n-diethyl-2-oxoacetamide Chemical compound C12=CC=CC=C2NC2=C1C=CC1=C2NC=C1C(=O)C(=O)N(CC)CC NOFRRBJDVTZROX-UHFFFAOYSA-N 0.000 claims description 2
- BFKLLTADWGLXEV-UHFFFAOYSA-N 2-(1,10-dihydropyrrolo[2,3-a]carbazol-3-yl)-n,n-diethylethanamine Chemical compound C12=CC=CC=C2NC2=C1C=CC1=C2NC=C1CCN(CC)CC BFKLLTADWGLXEV-UHFFFAOYSA-N 0.000 claims description 2
- KNAUNTGIXRQKQH-UHFFFAOYSA-N 2-(1,10-dihydropyrrolo[2,3-a]carbazol-3-yl)ethanol Chemical compound C12=CC=CC=C2NC2=C1C=CC1=C2NC=C1CCO KNAUNTGIXRQKQH-UHFFFAOYSA-N 0.000 claims description 2
- OETQQPPEDZRIIN-UHFFFAOYSA-N 2-(diethylamino)-1-(1,10-dihydropyrrolo[2,3-a]carbazol-3-yl)ethanol Chemical compound C12=CC=CC=C2NC2=C1C=CC1=C2NC=C1C(O)CN(CC)CC OETQQPPEDZRIIN-UHFFFAOYSA-N 0.000 claims description 2
- HFIDQKQLIDQTPU-UHFFFAOYSA-N 3-formyl-1,10-dihydropyrrolo[2,3-a]carbazole-7-carbonitrile Chemical compound C12=CC(C#N)=CC=C2NC2=C1C=CC1=C2NC=C1C=O HFIDQKQLIDQTPU-UHFFFAOYSA-N 0.000 claims description 2
- AVQHVNUSRJCQBY-UHFFFAOYSA-N 6,8-dichloro-1,10-dihydropyrrolo[2,3-a]carbazole Chemical compound C=1C(Cl)=CC(Cl)=C2C=1NC1=C2C=CC2=C1NC=C2 AVQHVNUSRJCQBY-UHFFFAOYSA-N 0.000 claims description 2
- XPFWHDMJBYQBFR-UHFFFAOYSA-N 6-bromo-1,10-dihydropyrrolo[2,3-a]carbazole Chemical compound C1=2C(Br)=CC=CC=2NC2=C1C=CC1=C2NC=C1 XPFWHDMJBYQBFR-UHFFFAOYSA-N 0.000 claims description 2
- CUNJCJHHSCBIHX-UHFFFAOYSA-N 7-(2,4-difluorophenyl)-1,10-dihydropyrrolo[2,3-a]carbazole Chemical compound FC1=CC(F)=CC=C1C1=CC=C(NC=2C=3NC=CC=3C=CC=22)C2=C1 CUNJCJHHSCBIHX-UHFFFAOYSA-N 0.000 claims description 2
- WHGSSVUZVLJLCM-UHFFFAOYSA-N 7-(3-methoxyphenyl)-1,10-dihydropyrrolo[2,3-a]carbazole Chemical compound COC1=CC=CC(C=2C=C3C4=C(C=5NC=CC=5C=C4)NC3=CC=2)=C1 WHGSSVUZVLJLCM-UHFFFAOYSA-N 0.000 claims description 2
- QATLODFZJKYGRA-UHFFFAOYSA-N 7-(3-methoxyphenyl)-1,10-dihydropyrrolo[2,3-a]carbazole-3-carbaldehyde Chemical compound COC1=CC=CC(C=2C=C3C4=C(C=5NC=C(C=O)C=5C=C4)NC3=CC=2)=C1 QATLODFZJKYGRA-UHFFFAOYSA-N 0.000 claims description 2
- NMENUZJNIUHBPP-UHFFFAOYSA-N 7-(4-fluorophenyl)-1,10-dihydropyrrolo[2,3-a]carbazole Chemical compound C1=CC(F)=CC=C1C1=CC=C(NC=2C=3NC=CC=3C=CC=22)C2=C1 NMENUZJNIUHBPP-UHFFFAOYSA-N 0.000 claims description 2
- QLMWVRUUEQQJKG-UHFFFAOYSA-N 7-(4-fluorophenyl)-1,10-dihydropyrrolo[2,3-a]carbazole-3-carbaldehyde Chemical compound C1=CC(F)=CC=C1C1=CC=C(NC=2C=3NC=C(C=O)C=3C=CC=22)C2=C1 QLMWVRUUEQQJKG-UHFFFAOYSA-N 0.000 claims description 2
- XHTYPHZPQFUXGM-UHFFFAOYSA-N 7-[4-(trifluoromethoxy)phenyl]-1,10-dihydropyrrolo[2,3-a]carbazole Chemical compound C1=CC(OC(F)(F)F)=CC=C1C1=CC=C(NC=2C=3NC=CC=3C=CC=22)C2=C1 XHTYPHZPQFUXGM-UHFFFAOYSA-N 0.000 claims description 2
- DJGGSFPUGZBESU-UHFFFAOYSA-N 7-[4-(trifluoromethyl)phenyl]-1,10-dihydropyrrolo[2,3-a]carbazole Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=C(NC=2C=3NC=CC=3C=CC=22)C2=C1 DJGGSFPUGZBESU-UHFFFAOYSA-N 0.000 claims description 2
- QPAADJFMYAMJHD-UHFFFAOYSA-N 7-nitro-1,10-dihydropyrrolo[2,3-a]carbazole Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC2=C1C=CC1=C2NC=C1 QPAADJFMYAMJHD-UHFFFAOYSA-N 0.000 claims description 2
- UJHXFAONXJTHBT-UHFFFAOYSA-N 7-nitro-1,10-dihydropyrrolo[2,3-a]carbazole-3-carbaldehyde Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC2=C1C=CC1=C2NC=C1C=O UJHXFAONXJTHBT-UHFFFAOYSA-N 0.000 claims description 2
- CFOKSEVBPFFBCJ-UHFFFAOYSA-N 7-phenyl-1,10-dihydropyrrolo[2,3-a]carbazole Chemical compound C=1C=C2NC3=C4NC=CC4=CC=C3C2=CC=1C1=CC=CC=C1 CFOKSEVBPFFBCJ-UHFFFAOYSA-N 0.000 claims description 2
- KRUYGAKMSWKQDA-UHFFFAOYSA-N 8-bromo-1,10-dihydropyrrolo[2,3-a]carbazole Chemical compound C=1C(Br)=CC=C2C=1NC1=C2C=CC2=C1NC=C2 KRUYGAKMSWKQDA-UHFFFAOYSA-N 0.000 claims description 2
- CIJBLVRHZSSVIC-UHFFFAOYSA-N 8-methyl-1,10-dihydropyrrolo[2,3-a]carbazole Chemical compound C=1C(C)=CC=C2C=1NC1=C2C=CC2=C1NC=C2 CIJBLVRHZSSVIC-UHFFFAOYSA-N 0.000 claims description 2
- UCZBSVKFYCHQCO-UHFFFAOYSA-N 9-(trifluoromethyl)-1,10-dihydropyrrolo[2,3-a]carbazole Chemical compound C12=CC=C3C=CNC3=C2NC2=C1C=CC=C2C(F)(F)F UCZBSVKFYCHQCO-UHFFFAOYSA-N 0.000 claims description 2
- FAGACQPJKMSVTQ-UHFFFAOYSA-N 9-ethyl-1,10-dihydropyrrolo[2,3-a]carbazole Chemical compound CCC1=CC=CC2=C1NC1=C2C=CC2=C1NC=C2 FAGACQPJKMSVTQ-UHFFFAOYSA-N 0.000 claims description 2
- OHGZLODAKBVSHS-UHFFFAOYSA-N 9-fluoro-1,10-dihydropyrrolo[2,3-a]carbazole Chemical compound C12=CC=C3C=CNC3=C2NC2=C1C=CC=C2F OHGZLODAKBVSHS-UHFFFAOYSA-N 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 2
- MVSOOVKNFXYVRW-UHFFFAOYSA-M OCC[N+](C)(C)C.[Cl-].[Zn] Chemical compound OCC[N+](C)(C)C.[Cl-].[Zn] MVSOOVKNFXYVRW-UHFFFAOYSA-M 0.000 claims description 2
- ZORRHJXCCLMGHU-UHFFFAOYSA-N ethyl 2-(1,10-dihydropyrrolo[2,3-a]carbazol-3-yl)-2-oxoacetate Chemical compound C12=CC=CC=C2NC2=C1C=CC1=C2NC=C1C(=O)C(=O)OCC ZORRHJXCCLMGHU-UHFFFAOYSA-N 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- LXOWHRBUEBSILH-UHFFFAOYSA-N methyl 2-(1,10-dihydropyrrolo[2,3-a]carbazol-3-yl)-2-oxoacetate Chemical compound C12=CC=CC=C2NC2=C1C=CC1=C2NC=C1C(=O)C(=O)OC LXOWHRBUEBSILH-UHFFFAOYSA-N 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims description 2
- MXZKCOUOYWSEKW-UHFFFAOYSA-N 1,10-dihydropyrrolo[2,3-a]carbazole-3-carboxamide Chemical compound C12=CC=CC=C2NC2=C1C=CC1=C2NC=C1C(=O)N MXZKCOUOYWSEKW-UHFFFAOYSA-N 0.000 claims 3
- VMYHTCGHQHXKSV-UHFFFAOYSA-N 2-(1,10-dihydropyrrolo[2,3-a]carbazol-3-yl)-N,N-diethyl-2-hydroxyiminoacetamide Chemical compound CCN(CC)C(=O)C(=NO)c1c[nH]c2c1ccc1c3ccccc3[nH]c21 VMYHTCGHQHXKSV-UHFFFAOYSA-N 0.000 claims 1
- OPYBLXOBBRQZQB-UHFFFAOYSA-N 7-fluoro-1,10-dihydropyrrolo[2,3-a]carbazole Chemical compound C12=CC(F)=CC=C2NC2=C1C=CC1=C2NC=C1 OPYBLXOBBRQZQB-UHFFFAOYSA-N 0.000 claims 1
- BSTRQWDVQRUDGP-UHFFFAOYSA-N 9-bromo-1,10-dihydropyrrolo[2,3-a]carbazole Chemical compound C12=CC=C3C=CNC3=C2NC2=C1C=CC=C2Br BSTRQWDVQRUDGP-UHFFFAOYSA-N 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 14
- 108010083755 proto-oncogene proteins pim Proteins 0.000 abstract description 8
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 174
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 80
- 238000005481 NMR spectroscopy Methods 0.000 description 67
- 239000007787 solid Substances 0.000 description 66
- 238000001819 mass spectrum Methods 0.000 description 52
- 238000002844 melting Methods 0.000 description 50
- 230000008018 melting Effects 0.000 description 50
- 229910003827 NRaRb Inorganic materials 0.000 description 44
- 238000005160 1H NMR spectroscopy Methods 0.000 description 36
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 34
- 239000000243 solution Substances 0.000 description 32
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 26
- 239000007864 aqueous solution Substances 0.000 description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 23
- 238000004587 chromatography analysis Methods 0.000 description 23
- 239000000741 silica gel Substances 0.000 description 22
- 229910002027 silica gel Inorganic materials 0.000 description 22
- 108091000080 Phosphotransferase Proteins 0.000 description 21
- 102000020233 phosphotransferase Human genes 0.000 description 21
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- 239000011780 sodium chloride Substances 0.000 description 13
- 238000010898 silica gel chromatography Methods 0.000 description 12
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- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- RGXCTRIQQODGIZ-UHFFFAOYSA-O isodesmosine Chemical compound OC(=O)C(N)CCCC[N+]1=CC(CCC(N)C(O)=O)=CC(CCC(N)C(O)=O)=C1CCCC(N)C(O)=O RGXCTRIQQODGIZ-UHFFFAOYSA-O 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- LZNLYVWOSKOHPZ-UHFFFAOYSA-N n,n-diethyl-2-oxoacetamide Chemical compound CCN(CC)C(=O)C=O LZNLYVWOSKOHPZ-UHFFFAOYSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- QNDVLZJODHBUFM-WFXQOWMNSA-N okadaic acid Chemical compound C([C@H](O1)[C@H](C)/C=C/[C@H]2CC[C@@]3(CC[C@H]4O[C@@H](C([C@@H](O)[C@@H]4O3)=C)[C@@H](O)C[C@H](C)[C@@H]3[C@@H](CC[C@@]4(OCCCC4)O3)C)O2)C(C)=C[C@]21O[C@H](C[C@@](C)(O)C(O)=O)CC[C@H]2O QNDVLZJODHBUFM-WFXQOWMNSA-N 0.000 description 1
- VEFJHAYOIAAXEU-UHFFFAOYSA-N okadaic acid Natural products CC(CC(O)C1OC2CCC3(CCC(O3)C=CC(C)C4CC(=CC5(OC(CC(C)(O)C(=O)O)CCC5O)O4)C)OC2C(O)C1C)C6OC7(CCCCO7)CCC6C VEFJHAYOIAAXEU-UHFFFAOYSA-N 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- JOVOSQBPPZZESK-UHFFFAOYSA-N phenylhydrazine hydrochloride Chemical class Cl.NNC1=CC=CC=C1 JOVOSQBPPZZESK-UHFFFAOYSA-N 0.000 description 1
- 229940038531 phenylhydrazine hydrochloride Drugs 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 108010056274 polo-like kinase 1 Proteins 0.000 description 1
- YSVQLWJDHYBITL-UHFFFAOYSA-N ppse Chemical compound C[Si](C)(C)OP(=O)=O YSVQLWJDHYBITL-UHFFFAOYSA-N 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
- 230000037425 regulation of transcription Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 150000003303 ruthenium Chemical class 0.000 description 1
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
- 229960002930 sirolimus Drugs 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 229920000685 trimethylsilyl polyphosphate Polymers 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 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
- A61K31/407—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 other heterocyclic ring systems, e.g. ketorolac, physostigmine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Epidemiology (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Oncology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0803752A FR2933409B1 (fr) | 2008-07-03 | 2008-07-03 | NOUVEAUX PYRROLO °2,3-a! CARBAZOLES ET LEUR UTILISATION COMME INHIBITEURS DES KINASES PIM |
| FR0803752 | 2008-07-03 | ||
| PCT/FR2009/000788 WO2010000978A1 (fr) | 2008-07-03 | 2009-06-25 | NOUVEAUX PYRROLO [2,3-a] CARBAZOLES ET LEUR UTILISATION COMME INHIBITEURS DES KINASES PIM |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2729690A1 true CA2729690A1 (fr) | 2010-01-07 |
Family
ID=40328682
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2729690A Abandoned CA2729690A1 (fr) | 2008-07-03 | 2009-06-25 | Nouveaux pyrrolo [2,3-a] carbazoles et leur utilisation comme inhibiteurs des kinases pim |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US8481586B2 (https=) |
| EP (1) | EP2326649B1 (https=) |
| JP (1) | JP5663476B2 (https=) |
| AT (1) | ATE551344T1 (https=) |
| CA (1) | CA2729690A1 (https=) |
| FR (1) | FR2933409B1 (https=) |
| WO (1) | WO2010000978A1 (https=) |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2455382B1 (en) | 2005-12-13 | 2016-10-26 | Incyte Holdings Corporation | Heteroaryl substituted pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidines as Janus kinase inhibitors |
| EP3070090B1 (en) | 2007-06-13 | 2018-12-12 | Incyte Holdings Corporation | Use of salts of the janus kinase inhibitor (r)-3-(4-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-1h- pyrazol-1-yl)-3- cyclopentylpropanenitrile |
| SG176111A1 (en) | 2009-05-22 | 2011-12-29 | Incyte Corp | 3-[4-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-1h-pyrazol-1-yl]octane- or heptane-nitrile as jak inhibitors |
| JP5775070B2 (ja) | 2009-05-22 | 2015-09-09 | インサイト・コーポレイションＩｎｃｙｔｅ Ｃｏｒｐｏｒａｔｉｏｎ | ヤヌスキナーゼ阻害剤としてのピラゾール−４−イル−ピロロ［２，３−ｄ］ピリミジンおよびピロール−３−イル−ピロロ［２，３−ｄ］ピリミジンのＮ−（ヘテロ）アリール−ピロリジン誘導体 |
| AR078012A1 (es) | 2009-09-01 | 2011-10-05 | Incyte Corp | Derivados heterociclicos de las pirazol-4-il- pirrolo (2,3-d) pirimidinas como inhibidores de la quinasa janus |
| PT3354652T (pt) | 2010-03-10 | 2020-07-20 | Incyte Holdings Corp | Derivados de piperidin-4-ilazetidina como inibidores de jak1 |
| RS54824B1 (sr) | 2010-05-21 | 2016-10-31 | Incyte Holdings Corp | Topikalna formulacija za inhibiciju jak-a |
| CA2818542A1 (en) | 2010-11-19 | 2012-05-24 | Incyte Corporation | Cyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as jak inhibitors |
| WO2012068440A1 (en) | 2010-11-19 | 2012-05-24 | Incyte Corporation | Heterocyclic-substituted pyrrolopyridines and pyrrolopyrimidines as jak inhibitors |
| MY165963A (en) | 2011-06-20 | 2018-05-18 | Incyte Holdings Corp | Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as jak inhibitors |
| EP2734205B1 (en) | 2011-07-21 | 2018-03-21 | Tolero Pharmaceuticals, Inc. | Heterocyclic protein kinase inhibitors |
| TW201313721A (zh) | 2011-08-18 | 2013-04-01 | Incyte Corp | 作為ｊａｋ抑制劑之環己基氮雜環丁烷衍生物 |
| UA111854C2 (uk) | 2011-09-07 | 2016-06-24 | Інсайт Холдінгс Корпорейшн | Способи і проміжні сполуки для отримання інгібіторів jak |
| KR101488565B1 (ko) | 2011-12-07 | 2015-02-03 | 주식회사 두산 | 유기 발광 화합물 및 이를 이용한 유기 전계 발광 소자 |
| TW201406761A (zh) | 2012-05-18 | 2014-02-16 | Incyte Corp | 做爲ｊａｋ抑制劑之哌啶基環丁基取代之吡咯并吡啶及吡咯并嘧啶衍生物 |
| KR101452579B1 (ko) | 2012-08-17 | 2014-10-21 | 주식회사 두산 | 신규 화합물 및 이를 포함하는 유기 전계 발광 소자 |
| KR101537436B1 (ko) * | 2012-08-17 | 2015-07-17 | 주식회사 두산 | 신규 화합물 및 이를 포함하는 유기 전계 발광 소자 |
| CN113384546A (zh) | 2012-11-15 | 2021-09-14 | 因赛特公司 | 鲁索利替尼的缓释剂型 |
| JP6437452B2 (ja) | 2013-01-14 | 2018-12-12 | インサイト・ホールディングス・コーポレイションＩｎｃｙｔｅ Ｈｏｌｄｉｎｇｓ Ｃｏｒｐｏｒａｔｉｏｎ | Ｐｉｍキナーゼ阻害剤として有用な二環式芳香族カルボキサミド化合物 |
| RS60244B1 (sr) | 2013-01-15 | 2020-06-30 | Incyte Holdings Corp | Jedinjenja tiazolkarboksamida i piridinkarboksamida korisna kao inhibitori pim kinaze |
| FR3001219A1 (fr) * | 2013-01-22 | 2014-07-25 | Centre Nat Rech Scient | Inhibiteurs de kinases |
| WO2014138168A1 (en) | 2013-03-06 | 2014-09-12 | Incyte Corporation | Processes and intermediates for making a jak inhibitor |
| SG10201801069QA (en) | 2013-08-07 | 2018-03-28 | Incyte Corp | Sustained release dosage forms for a jak1 inhibitor |
| CN105658653A (zh) | 2013-08-23 | 2016-06-08 | 因赛特公司 | 可用作pim激酶抑制剂的呋喃并-和噻吩并-吡啶甲酰胺化合物 |
| US9498467B2 (en) | 2014-05-30 | 2016-11-22 | Incyte Corporation | Treatment of chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) by inhibitors of JAK1 |
| US9580418B2 (en) | 2014-07-14 | 2017-02-28 | Incyte Corporation | Bicyclic aromatic carboxamide compounds useful as Pim kinase inhibitors |
| WO2016010897A1 (en) | 2014-07-14 | 2016-01-21 | Incyte Corporation | Bicyclic heteroaromatic carboxamide compounds useful as pim kinase inhibitors |
| WO2016196244A1 (en) | 2015-05-29 | 2016-12-08 | Incyte Corporation | Pyridineamine compounds useful as pim kinase inhibitors |
| TWI734699B (zh) | 2015-09-09 | 2021-08-01 | 美商英塞特公司 | Ｐｉｍ激酶抑制劑之鹽 |
| US9920032B2 (en) | 2015-10-02 | 2018-03-20 | Incyte Corporation | Heterocyclic compounds useful as pim kinase inhibitors |
| AR113922A1 (es) | 2017-12-08 | 2020-07-01 | Incyte Corp | Terapia de combinación de dosis baja para el tratamiento de neoplasias mieloproliferativas |
| EA202091830A1 (ru) | 2018-01-30 | 2020-12-29 | Инсайт Корпорейшн | Способы и промежуточные соединения для получения ингибитора jak |
| MD3773593T2 (ro) | 2018-03-30 | 2024-10-31 | Incyte Corp | Tratament hidradenitei supurative utilizând inhibitori ai JAK |
| CN117838695A (zh) | 2018-04-13 | 2024-04-09 | 住友制药肿瘤公司 | 用于治疗骨髓增殖性肿瘤和与癌症相关的纤维化的pim激酶抑制剂 |
| NZ778055A (en) | 2019-02-12 | 2025-11-28 | Sumitomo Pharma America Inc | Formulations comprising heterocyclic protein kinase inhibitors |
| US11833155B2 (en) | 2020-06-03 | 2023-12-05 | Incyte Corporation | Combination therapy for treatment of myeloproliferative neoplasms |
| EP4611753A1 (en) | 2022-10-31 | 2025-09-10 | Sumitomo Pharma America, Inc. | Pim1 inhibitor for treating myeloproliferative neoplasms |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101316847A (zh) * | 2005-10-06 | 2008-12-03 | 先灵公司 | 用作蛋白激酶抑制剂的吡唑并(1,5a)嘧啶化合物 |
| TW200804386A (en) * | 2005-11-10 | 2008-01-16 | Schering Corp | Imidazopyrazines as protein kinase inhibitors |
-
2008
- 2008-07-03 FR FR0803752A patent/FR2933409B1/fr not_active Expired - Fee Related
-
2009
- 2009-06-25 US US13/002,423 patent/US8481586B2/en not_active Expired - Fee Related
- 2009-06-25 EP EP09772661A patent/EP2326649B1/fr not_active Not-in-force
- 2009-06-25 CA CA2729690A patent/CA2729690A1/fr not_active Abandoned
- 2009-06-25 AT AT09772661T patent/ATE551344T1/de active
- 2009-06-25 JP JP2011515526A patent/JP5663476B2/ja not_active Expired - Fee Related
- 2009-06-25 WO PCT/FR2009/000788 patent/WO2010000978A1/fr not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| ATE551344T1 (de) | 2012-04-15 |
| JP5663476B2 (ja) | 2015-02-04 |
| EP2326649A1 (fr) | 2011-06-01 |
| EP2326649B1 (fr) | 2012-03-28 |
| FR2933409A1 (fr) | 2010-01-08 |
| JP2011526610A (ja) | 2011-10-13 |
| WO2010000978A1 (fr) | 2010-01-07 |
| US20110263669A1 (en) | 2011-10-27 |
| US8481586B2 (en) | 2013-07-09 |
| FR2933409B1 (fr) | 2010-08-27 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20140526 |
|
| FZDE | Discontinued |
Effective date: 20161123 |