AU2013299922B2 - Process for the preparation of heterocyclic ester derivatives - Google Patents
Process for the preparation of heterocyclic ester derivatives Download PDFInfo
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- AU2013299922B2 AU2013299922B2 AU2013299922A AU2013299922A AU2013299922B2 AU 2013299922 B2 AU2013299922 B2 AU 2013299922B2 AU 2013299922 A AU2013299922 A AU 2013299922A AU 2013299922 A AU2013299922 A AU 2013299922A AU 2013299922 B2 AU2013299922 B2 AU 2013299922B2
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- 238000000034 method Methods 0.000 title claims abstract description 134
- 230000008569 process Effects 0.000 title claims abstract description 123
- 238000002360 preparation method Methods 0.000 title claims abstract description 38
- -1 heterocyclic ester Chemical class 0.000 title abstract description 27
- 150000001875 compounds Chemical class 0.000 claims abstract description 143
- 239000000203 mixture Substances 0.000 claims description 97
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 claims description 70
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims description 56
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 56
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 49
- 230000008878 coupling Effects 0.000 claims description 38
- 238000010168 coupling process Methods 0.000 claims description 38
- 238000005859 coupling reaction Methods 0.000 claims description 38
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 32
- 239000003446 ligand Substances 0.000 claims description 26
- 150000002941 palladium compounds Chemical class 0.000 claims description 25
- 150000007530 organic bases Chemical group 0.000 claims description 24
- 239000007789 gas Substances 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 239000003960 organic solvent Substances 0.000 claims description 13
- 229910052794 bromium Inorganic materials 0.000 claims description 12
- 150000007529 inorganic bases Chemical class 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- 239000003054 catalyst Substances 0.000 claims description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 229910052751 metal Inorganic materials 0.000 claims description 4
- 239000002184 metal Substances 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 229910052763 palladium Inorganic materials 0.000 claims description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 9
- WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 claims 2
- 229910052721 tungsten Inorganic materials 0.000 claims 2
- 239000010937 tungsten Substances 0.000 claims 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract description 16
- 238000003786 synthesis reaction Methods 0.000 abstract description 12
- 108010058398 Macrophage Colony-Stimulating Factor Receptor Proteins 0.000 abstract description 4
- 239000003112 inhibitor Substances 0.000 abstract description 4
- 239000000543 intermediate Substances 0.000 abstract description 4
- 239000005483 tyrosine kinase inhibitor Substances 0.000 abstract description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 27
- 239000002904 solvent Substances 0.000 description 26
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 23
- 239000000047 product Substances 0.000 description 22
- 239000002253 acid Substances 0.000 description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 13
- 239000007787 solid Substances 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 10
- 208000024891 symptom Diseases 0.000 description 9
- 201000010099 disease Diseases 0.000 description 8
- 238000011065 in-situ storage Methods 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 5
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 5
- 239000003999 initiator Substances 0.000 description 5
- 125000006239 protecting group Chemical group 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 235000015320 potassium carbonate Nutrition 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 150000005829 chemical entities Chemical class 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000011031 large-scale manufacturing process Methods 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical group CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- QCXJEYYXVJIFCE-UHFFFAOYSA-N 4-acetamidobenzoic acid Chemical compound CC(=O)NC1=CC=C(C(O)=O)C=C1 QCXJEYYXVJIFCE-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 0 CC(C)=NC(*)=C(C)* Chemical compound CC(C)=NC(*)=C(C)* 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical group C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 150000001412 amines Chemical group 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- FQNHWXHRAUXLFU-UHFFFAOYSA-N carbon monoxide;tungsten Chemical group [W].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-] FQNHWXHRAUXLFU-UHFFFAOYSA-N 0.000 description 2
- 230000006315 carbonylation Effects 0.000 description 2
- 238000005810 carbonylation reaction Methods 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000004296 chiral HPLC Methods 0.000 description 2
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 2
- 239000012039 electrophile Substances 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 2
- 229940011051 isopropyl acetate Drugs 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 150000004692 metal hydroxides Chemical class 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
- PXQPEWDEAKTCGB-UHFFFAOYSA-N orotic acid Chemical compound OC(=O)C1=CC(=O)NC(=O)N1 PXQPEWDEAKTCGB-UHFFFAOYSA-N 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 239000010935 stainless steel Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N thiocyanic acid Chemical compound SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 2
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 description 1
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- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
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- 229940099584 lactobionate Drugs 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
- 229940099563 lactobionic acid Drugs 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N mandelic acid Chemical compound OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
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- 238000005259 measurement Methods 0.000 description 1
- 229910000000 metal hydroxide Inorganic materials 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- LRMHVVPPGGOAJQ-UHFFFAOYSA-N methyl nitrate Chemical compound CO[N+]([O-])=O LRMHVVPPGGOAJQ-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
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- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
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- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
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- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
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- 239000008177 pharmaceutical agent Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 1
- 238000004237 preparative chromatography Methods 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
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- 229960004889 salicylic acid Drugs 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
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- 239000000377 silicon dioxide Substances 0.000 description 1
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- 239000008247 solid mixture Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
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- 125000001424 substituent group Chemical group 0.000 description 1
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- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
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- 229940095064 tartrate Drugs 0.000 description 1
- 229950002757 teoclate Drugs 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
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- 125000003944 tolyl group Chemical group 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
- 150000003852 triazoles Chemical group 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
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- 229960000281 trometamol Drugs 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 238000010626 work up procedure Methods 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/0825—Preparations of compounds not comprising Si-Si or Si-cyano linkages
- C07F7/083—Syntheses without formation of a Si-C bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
- C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/10—Compounds having one or more C—Si linkages containing nitrogen having a Si-N linkage
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
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|---|---|---|---|
| US201261680412P | 2012-08-07 | 2012-08-07 | |
| US61/680,412 | 2012-08-07 | ||
| PCT/US2013/053595 WO2014025675A1 (en) | 2012-08-07 | 2013-08-05 | Process for the preparation of heterocyclic ester derivatives |
Publications (3)
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|---|---|
| AU2013299922A1 AU2013299922A1 (en) | 2015-02-12 |
| AU2013299922A8 AU2013299922A8 (en) | 2015-03-12 |
| AU2013299922B2 true AU2013299922B2 (en) | 2018-06-21 |
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| AU2013299922A Ceased AU2013299922B2 (en) | 2012-08-07 | 2013-08-05 | Process for the preparation of heterocyclic ester derivatives |
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| EP (1) | EP2882757B1 (enExample) |
| JP (1) | JP6359537B2 (enExample) |
| CN (1) | CN104870454B (enExample) |
| AR (1) | AR092071A1 (enExample) |
| AU (1) | AU2013299922B2 (enExample) |
| ES (1) | ES2608628T3 (enExample) |
| IN (1) | IN2015DN00659A (enExample) |
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| TW (1) | TWI608009B (enExample) |
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| WO (1) | WO2014025675A1 (enExample) |
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| CN104870454B (zh) * | 2012-08-07 | 2020-03-03 | 詹森药业有限公司 | 用于制备杂环酯衍生物的方法 |
| WO2018130443A1 (de) | 2017-01-10 | 2018-07-19 | Bayer Aktiengesellschaft | Heterocyclen-derivate als schädlingsbekämpfungsmittel |
Family Cites Families (97)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2466420A (en) | 1947-11-26 | 1949-04-05 | Eastman Kodak Co | Ketene condensation products with aldehydes |
| US3226394A (en) | 1964-06-16 | 1965-12-28 | Shulton Inc | Pyridylethylated anthranilamides and derivatives thereof |
| CH504416A (de) | 1966-12-05 | 1971-03-15 | Ciba Geigy Ag | Verfahren zur Herstellung von aromatischen Sulfamoylverbindungen |
| US4551540A (en) | 1983-01-17 | 1985-11-05 | Borg-Warner Chemicals, Inc. | Substituted 2,5-dimethylpyrroles |
| US5190541A (en) | 1990-10-17 | 1993-03-02 | Boston Scientific Corporation | Surgical instrument and method |
| ES2193143T3 (es) | 1992-03-05 | 2003-11-01 | Univ Texas | Uso de inmunoconjugados para la diagnosis y/o terapia de tumores vascularizaos. |
| US5474765A (en) | 1992-03-23 | 1995-12-12 | Ut Sw Medical Ctr At Dallas | Preparation and use of steroid-polyanionic polymer-based conjugates targeted to vascular endothelial cells |
| US5686472A (en) | 1992-10-29 | 1997-11-11 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
| US5593992A (en) | 1993-07-16 | 1997-01-14 | Smithkline Beecham Corporation | Compounds |
| EP0785937A1 (en) | 1994-10-14 | 1997-07-30 | Smithkline Beecham Plc | 2-(imidazol-4-yl)carbapeneme derivatives, intermediates thereof and use as antibacterials |
| ATE223180T1 (de) | 1995-04-19 | 2002-09-15 | Schneider Usa Inc | Beschichteter dilatator zur abgabe eines arzneistoffs |
| US6117432A (en) | 1995-04-20 | 2000-09-12 | Societe D'exploitation De Produits Pour Les Industries Chimiques (S.E.P.P.I.C.) | Therapeutic composition comprising an antigen or an in vivo generator of a compound comprising an amino acid sequence |
| TW349948B (en) | 1995-10-31 | 1999-01-11 | Janssen Pharmaceutica Nv | Farnesyl transferase inhibiting 2-quinolone derivatives |
| GB9523675D0 (en) | 1995-11-20 | 1996-01-24 | Celltech Therapeutics Ltd | Chemical compounds |
| KR100272676B1 (ko) | 1995-12-08 | 2000-11-15 | 디르크 반테 | 파르네실 단백질 트랜스퍼라제 억제 기능을 갖는 (이미다졸-5-일)메틸-2-퀴놀리논 유도체 |
| US5874442A (en) | 1995-12-22 | 1999-02-23 | Schering-Plough Corporation | Tricyclic amides useful for inhibition of G-protein function and for treatment of proliferative disease |
| US6011029A (en) | 1996-02-26 | 2000-01-04 | Bristol-Myers Squibb Company | Inhibitors of farnesyl protein transferase |
| US5702390A (en) | 1996-03-12 | 1997-12-30 | Ethicon Endo-Surgery, Inc. | Bioplar cutting and coagulation instrument |
| AU711936B2 (en) | 1996-08-09 | 1999-10-28 | Banyu Pharmaceutical Co., Ltd. | Stereoselective deoxygenation reaction |
| UA59384C2 (uk) | 1996-12-20 | 2003-09-15 | Пфайзер, Інк. | Похідні сульфонамідів та амідів як агоністи простагландину, фармацевтична композиція та способи лікування на їх основі |
| JP2001505548A (ja) | 1996-12-20 | 2001-04-24 | トヴァリシェストヴォ エス オグラニチェンノイ オトヴェトストヴェンノストジュ“タブジュファーム” | 凍結乾燥ハイドロクロライド−１β，１０β−エポキシ−１３−ジメチルアミノ−グアヤ−３（４）−エン−６，１２−オリドの生成方法および装置 |
| TW591030B (en) | 1997-03-10 | 2004-06-11 | Janssen Pharmaceutica Nv | Farnesyl transferase inhibiting 1,8-annelated quinolinone derivatives substituted with N- or C-linked imidazoles |
| US6177432B1 (en) | 1997-04-25 | 2001-01-23 | Janssen-Cilag S.A. | Farnesyltransferase inhibiting quinazolinones |
| TW491872B (en) | 1997-05-27 | 2002-06-21 | Ciba Sc Holding Ag | Block oligomers containing l-hydrocarbyloxy-2,2,6,6-tetramethyl-4- piperidyl groups as stabilizers for lower polyolefin |
| US6100254A (en) | 1997-10-10 | 2000-08-08 | Board Of Regents, The University Of Texas System | Inhibitors of protein tyrosine kinases |
| JP4022044B2 (ja) | 1998-03-05 | 2007-12-12 | フォーミュラ ワン アドミニストレイション リミテッド | データ通信システム |
| US6303654B1 (en) | 1998-03-12 | 2001-10-16 | Wisconsin Alumni Research Foundation | Acyclic monoterpenoid derivatives |
| AU5086499A (en) | 1998-07-01 | 2000-01-24 | Merck & Co., Inc. | Process for making farnesyl-protein transferase inhibitors |
| EP1097147A4 (en) | 1998-07-10 | 2001-11-21 | Merck & Co Inc | NEW ANGIOGENESIS INHIBITORS |
| AU4925499A (en) | 1998-08-27 | 2000-03-21 | Pfizer Products Inc. | Alkynyl-substituted quinolin-2-one derivatives useful as anticancer agents |
| ES2237125T3 (es) | 1998-08-27 | 2005-07-16 | Pfizer Products Inc. | Derivados de quinolin-2-ona utiles como agentes anticancerigenos. |
| GB9824579D0 (en) | 1998-11-10 | 1999-01-06 | Novartis Ag | Organic compounds |
| CZ302374B6 (cs) | 1998-12-23 | 2011-04-20 | Janssen Pharmaceutica N.V. | Derivát 1,2-anelovaného chinolinu, zpusob a meziprodukt pro jeho prípravu a farmaceutický prostredek s jeho obsahem |
| US6383790B1 (en) | 1999-01-11 | 2002-05-07 | Princeton University | High affinity protein kinase inhibitors |
| MXPA01010292A (es) | 1999-04-15 | 2002-10-23 | Squibb Bristol Myers Co | Inhibidores ciclicos de la proteina tirosina cinasa. |
| US7125875B2 (en) | 1999-04-15 | 2006-10-24 | Bristol-Myers Squibb Company | Cyclic protein tyrosine kinase inhibitors |
| US6342219B1 (en) | 1999-04-28 | 2002-01-29 | Board Of Regents, The University Of Texas System | Antibody compositions for selectively inhibiting VEGF |
| US6346625B1 (en) | 1999-06-23 | 2002-02-12 | Astrazeneca Ab | Protein kinase inhibitors |
| DE19962924A1 (de) | 1999-12-24 | 2001-07-05 | Bayer Ag | Substituierte Oxazolidinone und ihre Verwendung |
| EP1246823A1 (en) | 1999-12-28 | 2002-10-09 | Pharmacopeia, Inc. | Pyrimidine and triazine kinase inhibitors |
| FR2803592A1 (fr) | 2000-01-06 | 2001-07-13 | Aventis Cropscience Sa | Nouveaux derives de l'acide 3-hydroxypicolinique, leur procede de preparation et compositions fongicides les contenant. |
| US6558385B1 (en) | 2000-09-22 | 2003-05-06 | Tissuelink Medical, Inc. | Fluid-assisted medical device |
| US6692491B1 (en) | 2000-03-24 | 2004-02-17 | Scimed Life Systems, Inc. | Surgical methods and apparatus for positioning a diagnostic or therapeutic element around one or more pulmonary veins or other body structures |
| US6776796B2 (en) | 2000-05-12 | 2004-08-17 | Cordis Corportation | Antiinflammatory drug and delivery device |
| CA2424689A1 (en) | 2000-10-17 | 2002-04-25 | Merck & Co., Inc. | Orally active salts with tyrosine kinase activity |
| US6958243B2 (en) * | 2000-12-14 | 2005-10-25 | Biotage Ab | Organic reactions with CO generating materials |
| US7105682B2 (en) | 2001-01-12 | 2006-09-12 | Amgen Inc. | Substituted amine derivatives and methods of use |
| TWI238824B (en) | 2001-05-14 | 2005-09-01 | Novartis Ag | 4-amino-5-phenyl-7-cyclobutyl-pyrrolo[2,3-d]pyrimidine derivatives |
| WO2003024931A1 (en) | 2001-09-14 | 2003-03-27 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| US7101884B2 (en) | 2001-09-14 | 2006-09-05 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| TWI259081B (en) | 2001-10-26 | 2006-08-01 | Sugen Inc | Treatment of acute myeloid leukemia with indolinone compounds |
| CA2462657C (en) | 2001-10-30 | 2011-04-26 | Novartis Ag | Staurosporine derivatives as inhibitors of flt3 receptor tyrosine kinase activity |
| BR0215360A (pt) | 2001-12-27 | 2004-12-14 | Theravance Inc | Derivados de indolina úteis como inibidores de proteìna quinase |
| DE60317198T2 (de) | 2002-05-23 | 2008-12-04 | Cytopia Research Pty. Ltd., Richmond | Proteinkinaseinhibitoren |
| PE20040522A1 (es) | 2002-05-29 | 2004-09-28 | Novartis Ag | Derivados de diarilurea dependientes de la cinasa de proteina |
| MY141867A (en) | 2002-06-20 | 2010-07-16 | Vertex Pharma | Substituted pyrimidines useful as protein kinase inhibitors |
| GB0215676D0 (en) | 2002-07-05 | 2002-08-14 | Novartis Ag | Organic compounds |
| KR20050042478A (ko) | 2002-08-14 | 2005-05-09 | 버텍스 파마슈티칼스 인코포레이티드 | 프로테인 키나아제 억제제 및 이의 용도 |
| KR20050037585A (ko) | 2002-08-23 | 2005-04-22 | 카이론 코포레이션 | 벤지미다졸 퀴놀리논 및 그들의 사용 |
| WO2004022525A1 (en) | 2002-09-05 | 2004-03-18 | Neurosearch A/S | Amide derivatives and their use as chloride channel blockers |
| WO2004030635A2 (en) | 2002-10-03 | 2004-04-15 | Targegen, Inc. | Vasculostatic agents and methods of use thereof |
| JPWO2004039782A1 (ja) | 2002-10-29 | 2006-03-02 | 麒麟麦酒株式会社 | Ｆｌｔ３自己リン酸化を阻害するキノリン誘導体およびキナゾリン誘導体並びにそれらを含有する医薬組成物 |
| WO2004043389A2 (en) | 2002-11-13 | 2004-05-27 | Chiron Corporation | Methods of treating cancer and related methods |
| AR042052A1 (es) | 2002-11-15 | 2005-06-08 | Vertex Pharma | Diaminotriazoles utiles como inhibidores de proteinquinasas |
| ATE425160T1 (de) | 2002-12-18 | 2009-03-15 | Vertex Pharma | Benzisoxazolderivate, die sich als inhibitoren von proteinkinasen eigen |
| RU2005134659A (ru) | 2003-04-09 | 2007-05-27 | Джапан Тобакко Инк. (Jp) | Гетероароматическое пентациклическое соединение и его применение в медицине |
| US20050113566A1 (en) | 2003-04-25 | 2005-05-26 | Player Mark R. | Inhibitors of C-FMS kinase |
| US7790724B2 (en) | 2003-04-25 | 2010-09-07 | Janssen Pharmaceutica N.V. | c-fms kinase inhibitors |
| CA2536964A1 (en) | 2003-04-25 | 2004-11-11 | Ortho-Mcneil Pharmaceutical, Inc. | C-fms kinase inhibitors |
| US7427683B2 (en) * | 2003-04-25 | 2008-09-23 | Ortho-Mcneil Pharmaceutical, Inc. | c-fms kinase inhibitors |
| RU2345981C2 (ru) | 2003-07-28 | 2009-02-10 | Смитклайн Бичем Корпорейшн | ЦИКЛОАЛКИЛИДЕНОВЫЕ СОЕДИНЕНИЯ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ИХ ОСНОВЕ, ИХ ПРИМЕНЕНИЕ И СПОСОБ СЕЛЕКТИВНОГО СВЯЗЫВАНИЯ ERα- И ERβ-ЭСТРОГЕНОВЫХ РЕЦЕПТОРОВ |
| WO2005040139A2 (en) | 2003-10-23 | 2005-05-06 | Ab Science | 2-aminoaryloxazole compounds as tyrosine kinase inhibitors |
| GB0326601D0 (en) | 2003-11-14 | 2003-12-17 | Novartis Ag | Organic compounds |
| BRPI0507271A (pt) | 2004-01-30 | 2007-06-26 | Ab Science | 2-(3-substituìda-aril)amino-4-aril-tiazóis como inibidores de tirosina cinase |
| EP1807077B1 (en) | 2004-10-22 | 2016-11-23 | Janssen Pharmaceutica NV | Inhibitors of c-fms kinase |
| DE602005015742D1 (de) * | 2004-10-22 | 2009-09-10 | Janssen Pharmaceutica Nv | Aromatische amide als hemmer der c-fms-kinase |
| US7662837B2 (en) | 2004-10-22 | 2010-02-16 | Janssen Pharmaceutica N.V. | Inhibitors of c-fms kinase |
| US7645755B2 (en) | 2004-10-22 | 2010-01-12 | Janssen Pharmaceutical N.V. | Inhibitors of c-fms kinase |
| US20060281769A1 (en) | 2005-06-10 | 2006-12-14 | Baumann Christian A | Synergistic modulation of flt3 kinase using thienopyrimidine and thienopyridine kinase modulators |
| US20060281788A1 (en) | 2005-06-10 | 2006-12-14 | Baumann Christian A | Synergistic modulation of flt3 kinase using a flt3 inhibitor and a farnesyl transferase inhibitor |
| US20060281700A1 (en) | 2005-06-10 | 2006-12-14 | Baumann Christian A | Synergistic modulation of flt3 kinase using aminopyrimidines kinase modulators |
| US20060281771A1 (en) | 2005-06-10 | 2006-12-14 | Baumann Christian A | Synergistic modulation of flt3 kinase using aminoquinoline and aminoquinazoline kinase modulators |
| US20060281755A1 (en) | 2005-06-10 | 2006-12-14 | Baumann Christian A | Synergistic modulation of flt3 kinase using aminopyrimidines kinase modulators |
| JP2009511628A (ja) | 2005-10-18 | 2009-03-19 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | Ｆｌｔ３キナーゼの阻害方法 |
| ES2581600T3 (es) | 2006-04-20 | 2016-09-06 | Janssen Pharmaceutica, N.V. | Inhibidores de quinasa c-fms |
| US8697716B2 (en) | 2006-04-20 | 2014-04-15 | Janssen Pharmaceutica Nv | Method of inhibiting C-KIT kinase |
| NZ572073A (en) | 2006-04-20 | 2011-09-30 | Janssen Pharmaceutica Nv | Heterocyclic compounds as inhibitors of c-fms kinase |
| US8815867B2 (en) | 2006-04-20 | 2014-08-26 | Janssen Pharmaceutica Nv | Inhibitors of c-fms kinase |
| US20100298314A1 (en) * | 2006-12-20 | 2010-11-25 | Schering Corporation | Novel jnk inhibitors |
| WO2008138184A1 (fr) * | 2007-05-14 | 2008-11-20 | Shanghai Hengrui Pharmaceutical Co.Ltd. | Dérivés de pyrrolo-azacycles, leur procédé de fabrication et leur utilisation en tant qu'inhibiteurs de protéine kinases |
| JO3240B1 (ar) | 2007-10-17 | 2018-03-08 | Janssen Pharmaceutica Nv | c-fms مثبطات كيناز |
| EP2215482A2 (en) | 2007-10-31 | 2010-08-11 | Janssen Pharmaceutica N.V. | Biomarker for assessing response to fms treatment |
| AU2009334997A1 (en) * | 2008-12-30 | 2011-08-04 | Millennium Pharmaceuticals, Inc. | Heteroaryl compounds useful as Raf kinase inhibitors |
| JP2011026305A (ja) * | 2009-06-24 | 2011-02-10 | Daiichi Sankyo Co Ltd | イミダゾールカルボニル化合物を含有する医薬組成物 |
| RU2600927C2 (ru) * | 2009-09-28 | 2016-10-27 | Ф.Хоффманн-Ля Рош Аг | Бензоксазепиновые ингибиторы pi3k и способы применения |
| US9227971B2 (en) * | 2010-01-19 | 2016-01-05 | Merck Sharp & Dohme Corp. | Pyrazolo[1,5-a]pyrimidine compounds as mTOR inhibitors |
| CN104870454B (zh) * | 2012-08-07 | 2020-03-03 | 詹森药业有限公司 | 用于制备杂环酯衍生物的方法 |
-
2013
- 2013-08-05 CN CN201380041843.XA patent/CN104870454B/zh not_active Expired - Fee Related
- 2013-08-05 US US13/959,120 patent/US9303046B2/en active Active
- 2013-08-05 WO PCT/US2013/053595 patent/WO2014025675A1/en not_active Ceased
- 2013-08-05 AU AU2013299922A patent/AU2013299922B2/en not_active Ceased
- 2013-08-05 ES ES13748442.4T patent/ES2608628T3/es active Active
- 2013-08-05 EP EP13748442.4A patent/EP2882757B1/en not_active Not-in-force
- 2013-08-05 IN IN659DEN2015 patent/IN2015DN00659A/en unknown
- 2013-08-05 JP JP2015526601A patent/JP6359537B2/ja active Active
- 2013-08-06 JO JOP/2013/0238A patent/JO3185B1/ar active
- 2013-08-06 TW TW102128025A patent/TWI608009B/zh not_active IP Right Cessation
- 2013-08-07 AR ARP130102809A patent/AR092071A1/es not_active Application Discontinuation
- 2013-08-07 UY UY0001034973A patent/UY34973A/es not_active Application Discontinuation
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2016
- 2016-02-23 US US15/051,052 patent/US20160168170A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| HK1210617A1 (en) | 2016-04-29 |
| US20140046072A1 (en) | 2014-02-13 |
| EP2882757B1 (en) | 2016-10-05 |
| ES2608628T3 (es) | 2017-04-12 |
| IN2015DN00659A (enExample) | 2015-06-26 |
| JO3185B1 (ar) | 2018-03-08 |
| JP2015525796A (ja) | 2015-09-07 |
| AU2013299922A8 (en) | 2015-03-12 |
| JP6359537B2 (ja) | 2018-07-18 |
| CN104870454A (zh) | 2015-08-26 |
| EP2882757A1 (en) | 2015-06-17 |
| WO2014025675A1 (en) | 2014-02-13 |
| TWI608009B (zh) | 2017-12-11 |
| UY34973A (es) | 2014-02-28 |
| CN104870454B (zh) | 2020-03-03 |
| HK1209753A1 (en) | 2016-04-08 |
| US9303046B2 (en) | 2016-04-05 |
| AR092071A1 (es) | 2015-03-18 |
| US20160168170A1 (en) | 2016-06-16 |
| AU2013299922A1 (en) | 2015-02-12 |
| TW201427986A (zh) | 2014-07-16 |
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