AU2501600A - Omega-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors - Google Patents
Omega-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors Download PDFInfo
- Publication number
- AU2501600A AU2501600A AU25016/00A AU2501600A AU2501600A AU 2501600 A AU2501600 A AU 2501600A AU 25016/00 A AU25016/00 A AU 25016/00A AU 2501600 A AU2501600 A AU 2501600A AU 2501600 A AU2501600 A AU 2501600A
- Authority
- AU
- Australia
- Prior art keywords
- substituted
- phenyl
- acid
- heteroatoms selected
- halogen
- 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
- 235000013877 carbamide Nutrition 0.000 title claims description 200
- -1 diphenyl ureas Chemical class 0.000 title claims description 171
- 102000009929 raf Kinases Human genes 0.000 title claims description 22
- 108010077182 raf Kinases Proteins 0.000 title claims description 22
- 239000004305 biphenyl Substances 0.000 title description 3
- 235000010290 biphenyl Nutrition 0.000 title description 3
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 title description 3
- 229940043355 kinase inhibitor Drugs 0.000 title description 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 2
- 238000000034 method Methods 0.000 claims description 403
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 286
- 229910052757 nitrogen Inorganic materials 0.000 claims description 145
- 239000004202 carbamide Substances 0.000 claims description 143
- 229910052717 sulfur Inorganic materials 0.000 claims description 143
- 125000005842 heteroatom Chemical group 0.000 claims description 137
- 229910052736 halogen Inorganic materials 0.000 claims description 112
- 150000002367 halogens Chemical group 0.000 claims description 112
- 150000001875 compounds Chemical class 0.000 claims description 104
- 229910052799 carbon Chemical group 0.000 claims description 89
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 76
- 125000004432 carbon atom Chemical group C* 0.000 claims description 76
- 125000001424 substituent group Chemical group 0.000 claims description 69
- 125000005843 halogen group Chemical group 0.000 claims description 65
- 125000003118 aryl group Chemical group 0.000 claims description 44
- 125000000217 alkyl group Chemical group 0.000 claims description 43
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 41
- 229910052739 hydrogen Inorganic materials 0.000 claims description 39
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 37
- 239000001257 hydrogen Substances 0.000 claims description 36
- 125000001072 heteroaryl group Chemical group 0.000 claims description 35
- 125000004122 cyclic group Chemical group 0.000 claims description 34
- 125000003545 alkoxy group Chemical group 0.000 claims description 32
- 125000005554 pyridyloxy group Chemical group 0.000 claims description 31
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 30
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 27
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 25
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 24
- 229910052701 rubidium Inorganic materials 0.000 claims description 24
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
- 239000002253 acid Substances 0.000 claims description 20
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 20
- 150000003672 ureas Chemical class 0.000 claims description 20
- 125000002947 alkylene group Chemical group 0.000 claims description 19
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 18
- 150000001768 cations Chemical class 0.000 claims description 17
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 14
- 230000001404 mediated effect Effects 0.000 claims description 14
- 239000001301 oxygen Substances 0.000 claims description 14
- 125000004076 pyridyl group Chemical group 0.000 claims description 14
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 13
- 125000000623 heterocyclic group Chemical group 0.000 claims description 13
- 239000011593 sulfur Substances 0.000 claims description 13
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 12
- 229910003827 NRaRb Inorganic materials 0.000 claims description 12
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 12
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 12
- 125000001475 halogen functional group Chemical group 0.000 claims description 12
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 12
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims description 12
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 230000010261 cell growth Effects 0.000 claims description 8
- 235000015165 citric acid Nutrition 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 7
- 125000004429 atom Chemical group 0.000 claims description 7
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 7
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 claims description 6
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 6
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 claims description 6
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 6
- 239000005711 Benzoic acid Substances 0.000 claims description 6
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 6
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 6
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 claims description 6
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 6
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 6
- 125000001931 aliphatic group Chemical group 0.000 claims description 6
- 150000001447 alkali salts Chemical class 0.000 claims description 6
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 6
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 6
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 6
- 229940092714 benzenesulfonic acid Drugs 0.000 claims description 6
- 235000010233 benzoic acid Nutrition 0.000 claims description 6
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims description 6
- 239000001530 fumaric acid Substances 0.000 claims description 6
- 235000011087 fumaric acid Nutrition 0.000 claims description 6
- 150000007529 inorganic bases Chemical class 0.000 claims description 6
- 239000004310 lactic acid Substances 0.000 claims description 6
- 235000014655 lactic acid Nutrition 0.000 claims description 6
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 6
- 239000011976 maleic acid Substances 0.000 claims description 6
- 239000001630 malic acid Substances 0.000 claims description 6
- 235000011090 malic acid Nutrition 0.000 claims description 6
- 229960002510 mandelic acid Drugs 0.000 claims description 6
- 150000007522 mineralic acids Chemical class 0.000 claims description 6
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 claims description 6
- 150000007524 organic acids Chemical class 0.000 claims description 6
- 235000005985 organic acids Nutrition 0.000 claims description 6
- 150000007530 organic bases Chemical class 0.000 claims description 6
- 235000006408 oxalic acid Nutrition 0.000 claims description 6
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims description 6
- 229960004889 salicylic acid Drugs 0.000 claims description 6
- 239000011975 tartaric acid Substances 0.000 claims description 6
- 235000002906 tartaric acid Nutrition 0.000 claims description 6
- JNWMCRIBVQCVQU-UHFFFAOYSA-N 4-[4-[[2-methoxy-5-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C(=CC=C(C=3)C(F)(F)F)OC)=CC=2)=C1 JNWMCRIBVQCVQU-UHFFFAOYSA-N 0.000 claims description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
- WINHEDROZCCEOE-UHFFFAOYSA-N 4-[4-[[4-bromo-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Br)=CC=3)C(F)(F)F)=CC=2)=C1 WINHEDROZCCEOE-UHFFFAOYSA-N 0.000 claims description 3
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 claims description 3
- 125000002877 alkyl aryl group Chemical group 0.000 claims 23
- 125000003710 aryl alkyl group Chemical group 0.000 claims 23
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 12
- 150000002431 hydrogen Chemical class 0.000 claims 9
- 125000003342 alkenyl group Chemical group 0.000 claims 8
- 125000001188 haloalkyl group Chemical group 0.000 claims 7
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims 5
- 125000003106 haloaryl group Chemical group 0.000 claims 5
- 125000005347 halocycloalkyl group Chemical group 0.000 claims 5
- 239000001117 sulphuric acid Substances 0.000 claims 5
- 235000011149 sulphuric acid Nutrition 0.000 claims 5
- 125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 claims 4
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims 2
- KUJYWIMYUCLJRI-UHFFFAOYSA-N 1-(5-tert-butyl-2-methoxyphenyl)-3-[4-(1,3-dioxoisoindol-5-yl)oxyphenyl]urea Chemical compound COC1=CC=C(C(C)(C)C)C=C1NC(=O)NC(C=C1)=CC=C1OC1=CC=C(C(=O)NC2=O)C2=C1 KUJYWIMYUCLJRI-UHFFFAOYSA-N 0.000 claims 2
- FAZUYBMEZYMFMZ-UHFFFAOYSA-N 1-(5-tert-butyl-2-methoxyphenyl)-3-[4-[(1-oxo-2,3-dihydroisoindol-5-yl)oxy]phenyl]urea Chemical compound COC1=CC=C(C(C)(C)C)C=C1NC(=O)NC(C=C1)=CC=C1OC1=CC=C(C(=O)NC2)C2=C1 FAZUYBMEZYMFMZ-UHFFFAOYSA-N 0.000 claims 2
- XKZCZQICFCGORI-UHFFFAOYSA-N 3-[4-[(5-tert-butyl-2-methoxyphenyl)carbamoylamino]phenoxy]-n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC(OC=2C=CC(NC(=O)NC=3C(=CC=C(C=3)C(C)(C)C)OC)=CC=2)=C1 XKZCZQICFCGORI-UHFFFAOYSA-N 0.000 claims 2
- PZCQMBMLJHRIRJ-UHFFFAOYSA-N 4-[2-chloro-4-[[2-methoxy-5-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(OC=2C(=CC(NC(=O)NC=3C(=CC=C(C=3)C(F)(F)F)OC)=CC=2)Cl)=C1 PZCQMBMLJHRIRJ-UHFFFAOYSA-N 0.000 claims 2
- NMRPWERDAUJWLD-UHFFFAOYSA-N 4-[3-[[2-methoxy-5-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]pyridine-2-carboxamide Chemical compound COC1=CC=C(C(F)(F)F)C=C1NC(=O)NC1=CC=CC(OC=2C=C(N=CC=2)C(N)=O)=C1 NMRPWERDAUJWLD-UHFFFAOYSA-N 0.000 claims 2
- RSDXTEAFHPMIAZ-UHFFFAOYSA-N 4-[3-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=C(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)C=CC=2)=C1 RSDXTEAFHPMIAZ-UHFFFAOYSA-N 0.000 claims 2
- HRLTXHASHFPQAJ-UHFFFAOYSA-N 4-[3-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]pyridine-2-carboxamide Chemical compound C1=NC(C(=O)N)=CC(OC=2C=C(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)C=CC=2)=C1 HRLTXHASHFPQAJ-UHFFFAOYSA-N 0.000 claims 2
- GOAGFZRGKHLHRT-UHFFFAOYSA-N 4-[3-chloro-4-[[2-methoxy-5-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=C(Cl)C(NC(=O)NC=3C(=CC=C(C=3)C(F)(F)F)OC)=CC=2)=C1 GOAGFZRGKHLHRT-UHFFFAOYSA-N 0.000 claims 2
- QQZNUVIRTSPCLZ-UHFFFAOYSA-N 4-[4-[[2-methoxy-5-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]pyridine-2-carboxamide Chemical compound COC1=CC=C(C(F)(F)F)C=C1NC(=O)NC(C=C1)=CC=C1OC1=CC=NC(C(N)=O)=C1 QQZNUVIRTSPCLZ-UHFFFAOYSA-N 0.000 claims 2
- AMKGGWUQNQADDG-UHFFFAOYSA-N 4-[4-[[2-methoxy-5-(trifluoromethyl)phenyl]carbamoylamino]phenyl]sulfanyl-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(SC=2C=CC(NC(=O)NC=3C(=CC=C(C=3)C(F)(F)F)OC)=CC=2)=C1 AMKGGWUQNQADDG-UHFFFAOYSA-N 0.000 claims 2
- UAEWBZYTKIMYRQ-UHFFFAOYSA-N 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]pyridine-2-carboxamide Chemical compound C1=NC(C(=O)N)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 UAEWBZYTKIMYRQ-UHFFFAOYSA-N 0.000 claims 2
- JQRCJEFLYSNDOH-UHFFFAOYSA-N 4-[3-[[2-methoxy-5-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=C(NC(=O)NC=3C(=CC=C(C=3)C(F)(F)F)OC)C=CC=2)=C1 JQRCJEFLYSNDOH-UHFFFAOYSA-N 0.000 claims 1
- WZXCMMDJRYMKQT-UHFFFAOYSA-N 4-[3-[[4-bromo-3-(trifluoromethyl)phenyl]carbamoylamino]phenoxy]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=C(NC(=O)NC=3C=C(C(Br)=CC=3)C(F)(F)F)C=CC=2)=C1 WZXCMMDJRYMKQT-UHFFFAOYSA-N 0.000 claims 1
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- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- AEXDMFVPDVVSQJ-UHFFFAOYSA-N trifluoro(trifluoromethylsulfonyl)methane Chemical compound FC(F)(F)S(=O)(=O)C(F)(F)F AEXDMFVPDVVSQJ-UHFFFAOYSA-N 0.000 description 1
- MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical compound C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 description 1
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
- IARSSOVWSJAVSZ-UHFFFAOYSA-N tris(dimethylamino)sulfanium Chemical compound CN(C)[S+](N(C)C)N(C)C IARSSOVWSJAVSZ-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D211/78—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/192—Radicals derived from carboxylic acids from aromatic carboxylic acids
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
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- A—HUMAN NECESSITIES
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- C07D295/073—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by halogen atoms or nitro radicals with the ring nitrogen atoms and the substituents separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
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- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
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- C07D295/13—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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AU2004200722A AU2004200722B2 (en) | 1999-01-13 | 2004-02-24 | Omega-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
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US11587799P | 1999-01-13 | 1999-01-13 | |
US60115877 | 1999-01-13 | ||
US25726699A | 1999-02-25 | 1999-02-25 | |
US09257266 | 1999-02-25 | ||
US42522899A | 1999-10-22 | 1999-10-22 | |
US09425228 | 1999-10-22 | ||
PCT/US2000/000648 WO2000042012A1 (fr) | 1999-01-13 | 2000-01-12 | DIPHENYLUREES A SUBSTITUANTS φ-CARBOXYARYLES, INHIBITRICES DE KINASE RAF |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
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AU2004200722A Division AU2004200722B2 (en) | 1999-01-13 | 2004-02-24 | Omega-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
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AU2501600A true AU2501600A (en) | 2000-08-01 |
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AU25016/00A Abandoned AU2501600A (en) | 1999-01-13 | 2000-01-12 | Omega-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
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KR (3) | KR20070020158A (fr) |
CN (2) | CN1219764C (fr) |
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AT (2) | ATE321027T1 (fr) |
AU (1) | AU2501600A (fr) |
BG (1) | BG65945B1 (fr) |
BR (2) | BRPI0007487B8 (fr) |
CA (1) | CA2359510C (fr) |
CU (1) | CU23213A3 (fr) |
CY (2) | CY2200149T2 (fr) |
CZ (2) | CZ302846B6 (fr) |
DE (4) | DE122006000059I1 (fr) |
DK (1) | DK1140840T3 (fr) |
DZ (1) | DZ3004A1 (fr) |
EE (1) | EE04913B1 (fr) |
EG (1) | EG24407A (fr) |
ES (2) | ES2272203T3 (fr) |
GT (2) | GT200000002A (fr) |
HK (2) | HK1045504B (fr) |
HR (1) | HRP20010580B1 (fr) |
HU (2) | HU230863B1 (fr) |
IL (2) | IL144030A0 (fr) |
JO (1) | JO2373B1 (fr) |
LU (1) | LU91280I2 (fr) |
MA (1) | MA26038A1 (fr) |
ME (1) | MEP36908A (fr) |
MY (1) | MY138897A (fr) |
NL (1) | NL300242I2 (fr) |
NO (3) | NO321059B1 (fr) |
NZ (1) | NZ556598A (fr) |
PA (1) | PA8489701A1 (fr) |
PL (1) | PL215029B1 (fr) |
PT (2) | PT1140840E (fr) |
RS (1) | RS51497B (fr) |
SK (2) | SK285532B6 (fr) |
SV (1) | SV2001000004A (fr) |
TN (1) | TNSN00010A1 (fr) |
TR (1) | TR200102020T2 (fr) |
TW (1) | TWI269791B (fr) |
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EP1474393A1 (fr) | 2002-02-11 | 2004-11-10 | Bayer Pharmaceuticals Corporation | Aryle-urees en tant qu'inhibiteurs de kinase |
PE20040522A1 (es) * | 2002-05-29 | 2004-09-28 | Novartis Ag | Derivados de diarilurea dependientes de la cinasa de proteina |
KR20060132882A (ko) * | 2004-01-30 | 2006-12-22 | 메르크 파텐트 게엠베하 | 비스아릴우레아 유도체 |
TW200530236A (en) | 2004-02-23 | 2005-09-16 | Chugai Pharmaceutical Co Ltd | Heteroaryl phenylurea |
MY191349A (en) * | 2004-08-27 | 2022-06-17 | Bayer Pharmaceuticals Corp | New pharmaceutical compositions for the treatment of hyper-proliferative disorders |
BRPI0515944B1 (pt) * | 2004-09-29 | 2021-11-09 | Bayer Healthcare Llc | Processo para a preparação de 4-{4-[({[4-cloro-3-(trifluorometil)fe-nil]amino}carbonil) amino]fenóxi}nmetilpiridina-2-carboxamida |
DE102005015253A1 (de) * | 2005-04-04 | 2006-10-05 | Merck Patent Gmbh | Pyrazolderivate |
US8580798B2 (en) | 2005-12-21 | 2013-11-12 | Bayer Intellectual Property Gmbh | Substituted pyrimidine derivatives useful in the treatment of cancer and other disorders |
WO2008044688A1 (fr) * | 2006-10-11 | 2008-04-17 | Daiichi Sankyo Company, Limited | Dérivé de l'urée |
WO2008115263A2 (fr) * | 2007-03-20 | 2008-09-25 | Curis, Inc. | Inhibiteurs de la raf kinase contenant un fragment de liaison au zinc |
US8445687B2 (en) * | 2007-09-10 | 2013-05-21 | Cipla Limited | Process for the preparation of a RAF kinase inhibitor and intermediates for use in the process |
CN101372475B (zh) * | 2008-03-19 | 2012-01-04 | 南京工业大学 | 芳杂环取代的二苯脲类衍生物及其用途 |
CN101298427B (zh) * | 2008-06-26 | 2012-03-21 | 中国科学院广州生物医药与健康研究院 | 二芳基脲类化合物及其应用 |
TW201012467A (en) | 2008-09-16 | 2010-04-01 | Taiho Pharmaceutical Co Ltd | Antitumor agent containing 4-[[3,5-bis(trimethylsilyl)benzoyl]amino]benzoic acid |
CN103254126A (zh) * | 2008-09-19 | 2013-08-21 | 苏州泽璟生物制药有限公司 | 氘代的ω-二苯基脲及衍生物以及包含该化合物的药物组合物 |
CN101362717B (zh) * | 2008-09-28 | 2013-02-06 | 四川大学 | 4-(4-氨基苯胺基)-2-(甲基氨甲酰基)吡啶及其衍生物和它们的制备方法、用途 |
JO3101B1 (ar) * | 2008-12-02 | 2017-09-20 | Takeda Pharmaceuticals Co | مشتقات بنزوثيازول كعوامل مضادة للسرطان |
CN102216280B (zh) * | 2009-01-22 | 2014-06-18 | 沈阳药科大学 | 双芳基脲类衍生物及用途 |
JP5728499B2 (ja) * | 2010-02-05 | 2015-06-03 | アイアールエム・リミテッド・ライアビリティ・カンパニーIrm,Llc | タンパク質キナーゼ阻害剤としての化合物および組成物 |
CN102219733A (zh) * | 2010-04-14 | 2011-10-19 | 上海医药工业研究院 | 索拉非尼的制备方法 |
CN101830847B (zh) * | 2010-05-18 | 2012-10-10 | 张南 | 抗癌用化合物及制备方法 |
CN102617458A (zh) * | 2010-05-18 | 2012-08-01 | 张南 | 抗癌用化合物的制备方法 |
MX2013003695A (es) | 2010-10-01 | 2013-05-20 | Bayer Ip Gmbh | Combinaciones que contienen n-(2-arilamino) arilsulfonamida sustituida. |
CA2824028A1 (fr) * | 2011-01-06 | 2012-07-12 | Beta Pharma Canada Inc. | Nouvelles urees pour le traitement et la prevention du cancer |
CN102875460A (zh) * | 2012-05-17 | 2013-01-16 | 上海奥博生物医药技术有限公司 | 一种制备索拉非尼的方法 |
CN103508961B (zh) * | 2012-06-26 | 2015-07-22 | 中美冠科生物技术(太仓)有限公司 | 抗肿瘤药物 |
CN103408488A (zh) * | 2013-08-13 | 2013-11-27 | 张家港威胜生物医药有限公司 | 一种索拉非尼的优化合成方法 |
CN103435553A (zh) * | 2013-09-16 | 2013-12-11 | 中国药科大学 | 基于哌嗪结构的芳甲酰胺类Raf激酶抑制剂及其制备方法和用途 |
CN104672129B (zh) * | 2013-11-26 | 2019-06-25 | 广东东阳光药业有限公司 | 一种脲类化合物的制备方法 |
CN104974132B (zh) | 2014-04-08 | 2017-05-17 | 北大方正集团有限公司 | 多取代的吡啶化合物、制备方法、用途及药物组合物 |
CN104177292A (zh) * | 2014-08-08 | 2014-12-03 | 亿腾药业(泰州)有限公司 | 一种工业化生产甲苯磺酸索拉非尼多晶型ⅰ的方法 |
WO2016049774A1 (fr) * | 2014-10-03 | 2016-04-07 | The Royal Institution For The Advancement Of Learning/Mcgill University | Urée et composés à base de bis-urée et analogues de ceux-ci utiles dans le traitement de maladies ou trouble à médiation par récepteur des androgènes |
CN105348186B (zh) * | 2015-10-15 | 2018-05-22 | 青岛海洋生物医药研究院股份有限公司 | 氘代双芳基脲类化合物及其制备方法和在制备抗肿瘤的药物中的应用 |
CN105753841B (zh) * | 2016-01-18 | 2018-01-05 | 西安交通大学 | 一种n‑吲唑取代硫脲类衍生物及其制备方法和应用 |
CN105924390B (zh) * | 2016-05-19 | 2018-07-10 | 广州南新制药有限公司 | 一种美他非尼的合成方法 |
CN106699652B (zh) * | 2016-11-07 | 2020-11-13 | 天津大学 | 一种索拉非尼α-氨基丁酸盐及其制备方法 |
CN108264510A (zh) | 2017-01-02 | 2018-07-10 | 上海喆邺生物科技有限公司 | 一种选择性抑制激酶化合物及其用途 |
CN107417604A (zh) * | 2017-07-25 | 2017-12-01 | 新发药业有限公司 | 4‑取代吡啶‑2‑甲酰胺化合物及其制备方法与应用 |
CN114025755A (zh) * | 2019-04-12 | 2022-02-08 | 台湾卫生研究院 | 以杂环化合物作为激酶抑制剂的治疗用途 |
CN113831491B (zh) * | 2021-09-30 | 2023-03-24 | 南昌大学 | 一种嘧啶唑共价有机框架的制备方法及吸附应用 |
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SK286564B6 (sk) * | 1997-12-22 | 2009-01-07 | Bayer Corporation | Substituované arylmočoviny ako inhibítory rafkinázy a farmaceutický prípravok s ich obsahom |
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2005
- 2005-12-09 NO NO20055863A patent/NO337326B1/no not_active IP Right Cessation
-
2006
- 2006-07-11 JP JP2006190034A patent/JP4472669B2/ja not_active Expired - Lifetime
- 2006-07-13 HK HK06107837.6A patent/HK1087689A1/xx not_active IP Right Cessation
- 2006-09-26 BG BG109688A patent/BG65945B1/bg unknown
- 2006-10-12 NL NL300242C patent/NL300242I2/nl unknown
- 2006-10-13 LU LU91280C patent/LU91280I2/fr unknown
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2007
- 2007-01-05 NO NO2007002C patent/NO2007002I2/no unknown
- 2007-01-15 CY CY20072200001T patent/CY2200149T2/el unknown
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2010
- 2010-06-10 CY CY20101100512T patent/CY1110177T1/el unknown
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