JP5063351B2 - ピラゾールキナーゼモジュレーターおよび使用方法 - Google Patents
ピラゾールキナーゼモジュレーターおよび使用方法 Download PDFInfo
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- JP5063351B2 JP5063351B2 JP2007532443A JP2007532443A JP5063351B2 JP 5063351 B2 JP5063351 B2 JP 5063351B2 JP 2007532443 A JP2007532443 A JP 2007532443A JP 2007532443 A JP2007532443 A JP 2007532443A JP 5063351 B2 JP5063351 B2 JP 5063351B2
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- JP
- Japan
- Prior art keywords
- phenyl
- pyrazol
- urea
- compound
- methylpiperazin
- 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.)
- Expired - Fee Related
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- 108091000080 Phosphotransferase Proteins 0.000 title claims description 54
- 102000020233 phosphotransferase Human genes 0.000 title claims description 54
- 238000000034 method Methods 0.000 title claims description 49
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 title description 9
- 150000001875 compounds Chemical class 0.000 claims description 189
- -1 3,4-difluorophenyl Chemical group 0.000 claims description 90
- 125000000217 alkyl group Chemical group 0.000 claims description 74
- 230000000694 effects Effects 0.000 claims description 61
- 239000000203 mixture Substances 0.000 claims description 58
- 150000003839 salts Chemical class 0.000 claims description 58
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 claims description 56
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 claims description 55
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 48
- 101100335081 Mus musculus Flt3 gene Proteins 0.000 claims description 40
- 125000003118 aryl group Chemical group 0.000 claims description 40
- 201000010099 disease Diseases 0.000 claims description 40
- 125000000623 heterocyclic group Chemical group 0.000 claims description 40
- 229910052736 halogen Inorganic materials 0.000 claims description 24
- 150000002367 halogens Chemical class 0.000 claims description 24
- 125000003545 alkoxy group Chemical group 0.000 claims description 23
- 206010028980 Neoplasm Diseases 0.000 claims description 22
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 21
- 102000001253 Protein Kinase Human genes 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- 108060006633 protein kinase Proteins 0.000 claims description 19
- 239000003153 chemical reaction reagent Substances 0.000 claims description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- 201000011510 cancer Diseases 0.000 claims description 13
- 125000004076 pyridyl group Chemical group 0.000 claims description 13
- 125000001424 substituent group Chemical group 0.000 claims description 13
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 11
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 11
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 11
- 125000005843 halogen group Chemical group 0.000 claims description 11
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 238000012216 screening Methods 0.000 claims description 10
- 230000035755 proliferation Effects 0.000 claims description 9
- LUBJCRLGQSPQNN-UHFFFAOYSA-N 1-Phenylurea Chemical compound NC(=O)NC1=CC=CC=C1 LUBJCRLGQSPQNN-UHFFFAOYSA-N 0.000 claims description 8
- 230000002159 abnormal effect Effects 0.000 claims description 8
- 239000004202 carbamide Substances 0.000 claims description 8
- 230000001413 cellular effect Effects 0.000 claims description 8
- 208000035475 disorder Diseases 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 8
- 230000005764 inhibitory process Effects 0.000 claims description 7
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 238000001727 in vivo Methods 0.000 claims description 6
- BAHVZNVPKFIXEX-UHFFFAOYSA-N 1-[4-chloro-3-(trifluoromethyl)phenyl]-3-[4-[5-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-3-yl]phenyl]urea Chemical compound C1CN(C)CCN1C1=CC=C(NC(=N2)C3=NNC(=C3)C=3C=CC(NC(=O)NC=4C=C(C(Cl)=CC=4)C(F)(F)F)=CC=3)C2=C1 BAHVZNVPKFIXEX-UHFFFAOYSA-N 0.000 claims description 5
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- AMRFOQNZKTUVOQ-UHFFFAOYSA-N 1-[4-[5-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-3-yl]phenyl]-3-[4-(trifluoromethoxy)phenyl]urea Chemical compound C1CN(C)CCN1C1=CC=C(NC(=N2)C3=NNC(=C3)C=3C=CC(NC(=O)NC=4C=CC(OC(F)(F)F)=CC=4)=CC=3)C2=C1 AMRFOQNZKTUVOQ-UHFFFAOYSA-N 0.000 claims description 3
- FGTJWNITGBGXMZ-UHFFFAOYSA-N 1-[4-chloro-3-(trifluoromethyl)phenyl]-3-[4-[3-[4-(4-ethylpiperazin-1-yl)phenyl]-1h-pyrazol-5-yl]phenyl]urea Chemical compound C1CN(CC)CCN1C1=CC=C(C2=NNC(=C2)C=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)C=C1 FGTJWNITGBGXMZ-UHFFFAOYSA-N 0.000 claims description 3
- FOPKAHVFWRJAQO-QPJJXVBHSA-N 4-[(E)-2-[3-(3-chlorophenyl)-1H-pyrazol-5-yl]ethenyl]phenol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(C=2C=C(Cl)C=CC=2)=NN1 FOPKAHVFWRJAQO-QPJJXVBHSA-N 0.000 claims description 3
- MLIZWELCMQRQMI-UNXLUWIOSA-N 4-[(E)-2-[3-(4-chlorophenyl)-1H-pyrazol-5-yl]ethenyl]phenol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(C=2C=CC(Cl)=CC=2)=NN1 MLIZWELCMQRQMI-UNXLUWIOSA-N 0.000 claims description 3
- JAJQTJFZXCGZBY-FARCUNLSSA-N 4-[(E)-2-[3-[4-(4-methylpiperazin-1-yl)phenyl]-1H-pyrazol-5-yl]ethenyl]phenol Chemical compound C1CN(C)CCN1C1=CC=C(C2=NNC(\C=C\C=3C=CC(O)=CC=3)=C2)C=C1 JAJQTJFZXCGZBY-FARCUNLSSA-N 0.000 claims description 3
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
- 208000026278 immune system disease Diseases 0.000 claims description 3
- 238000000338 in vitro Methods 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- GVXMIDQHUUZGBO-UHFFFAOYSA-N 1-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-[4-[3-[4-(4-methylpiperazin-1-yl)phenyl]-1h-pyrazol-5-yl]phenyl]urea Chemical compound C1CN(C)CCN1C1=CC=C(C=2NN=C(C=2)C=2C=CC(NC(=O)NC=3C=C4OCCOC4=CC=3)=CC=2)C=C1 GVXMIDQHUUZGBO-UHFFFAOYSA-N 0.000 claims description 2
- WSAHYWLIUXWHPB-UHFFFAOYSA-N 1-(2,4-difluorophenyl)-3-[4-[3-[4-(4-methylpiperazin-1-yl)phenyl]-1h-pyrazol-5-yl]phenyl]urea Chemical compound C1CN(C)CCN1C1=CC=C(C2=NNC(=C2)C=2C=CC(NC(=O)NC=3C(=CC(F)=CC=3)F)=CC=2)C=C1 WSAHYWLIUXWHPB-UHFFFAOYSA-N 0.000 claims description 2
- AUBLOAIVSCNBKR-UHFFFAOYSA-N 1-(2,4-dimethoxyphenyl)-3-[4-[3-[4-(4-methylpiperazin-1-yl)phenyl]-1h-pyrazol-5-yl]phenyl]urea Chemical compound COC1=CC(OC)=CC=C1NC(=O)NC1=CC=C(C2=NNC(=C2)C=2C=CC(=CC=2)N2CCN(C)CC2)C=C1 AUBLOAIVSCNBKR-UHFFFAOYSA-N 0.000 claims description 2
- DOPNMZFJYLXNRT-UHFFFAOYSA-N 1-(2-fluorophenyl)-3-[4-[5-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-3-yl]phenyl]urea Chemical compound C1CN(C)CCN1C1=CC=C(NC(=N2)C3=NNC(=C3)C=3C=CC(NC(=O)NC=4C(=CC=CC=4)F)=CC=3)C2=C1 DOPNMZFJYLXNRT-UHFFFAOYSA-N 0.000 claims description 2
- YCVHHWGKQGAZFD-UHFFFAOYSA-N 1-(3,4-dichlorophenyl)-3-[4-[5-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-3-yl]phenyl]urea Chemical compound C1CN(C)CCN1C1=CC=C(NC(=N2)C3=NNC(=C3)C=3C=CC(NC(=O)NC=4C=C(Cl)C(Cl)=CC=4)=CC=3)C2=C1 YCVHHWGKQGAZFD-UHFFFAOYSA-N 0.000 claims description 2
- YHAOCCRRHJMMBF-UHFFFAOYSA-N 1-(3,4-dimethoxyphenyl)-3-[4-[5-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-3-yl]phenyl]urea Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)NC1=CC=C(C=2NN=C(C=2)C=2NC3=CC=C(C=C3N=2)N2CCN(C)CC2)C=C1 YHAOCCRRHJMMBF-UHFFFAOYSA-N 0.000 claims description 2
- TXZXAPSGPZZZDZ-UHFFFAOYSA-N 1-(3,4-dimethylphenyl)-3-[4-[3-[4-(4-methylpiperazin-1-yl)phenyl]-1h-pyrazol-5-yl]phenyl]urea Chemical compound C1CN(C)CCN1C1=CC=C(C=2NN=C(C=2)C=2C=CC(NC(=O)NC=3C=C(C)C(C)=CC=3)=CC=2)C=C1 TXZXAPSGPZZZDZ-UHFFFAOYSA-N 0.000 claims description 2
- PWIOZOJGSPTINN-UHFFFAOYSA-N 1-(3,5-dimethoxyphenyl)-3-[4-[5-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-3-yl]phenyl]urea Chemical compound COC1=CC(OC)=CC(NC(=O)NC=2C=CC(=CC=2)C=2NN=C(C=2)C=2NC3=CC(=CC=C3N=2)N2CCN(C)CC2)=C1 PWIOZOJGSPTINN-UHFFFAOYSA-N 0.000 claims description 2
- KUHLUPFMZODMCI-UHFFFAOYSA-N 1-(3-acetylphenyl)-3-[4-[5-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-3-yl]phenyl]urea Chemical compound C1CN(C)CCN1C1=CC=C(NC(=N2)C3=NNC(=C3)C=3C=CC(NC(=O)NC=4C=C(C=CC=4)C(C)=O)=CC=3)C2=C1 KUHLUPFMZODMCI-UHFFFAOYSA-N 0.000 claims description 2
- LLWVODYKLPKHMN-UHFFFAOYSA-N 1-(3-bromophenyl)-3-[4-[5-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-3-yl]phenyl]urea Chemical compound C1CN(C)CCN1C1=CC=C(N=C(N2)C3=NNC(=C3)C=3C=CC(NC(=O)NC=4C=C(Br)C=CC=4)=CC=3)C2=C1 LLWVODYKLPKHMN-UHFFFAOYSA-N 0.000 claims description 2
- WJNDOEISGQZYEY-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-[4-[5-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-3-yl]phenyl]urea Chemical compound C1CN(C)CCN1C1=CC=C(NC(=N2)C3=NNC(=C3)C=3C=CC(NC(=O)NC=4C=C(Cl)C=CC=4)=CC=3)C2=C1 WJNDOEISGQZYEY-UHFFFAOYSA-N 0.000 claims description 2
- NIROGIQQTUAATM-UHFFFAOYSA-N 1-(3-cyanophenyl)-3-[4-[5-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-3-yl]phenyl]urea Chemical compound C1CN(C)CCN1C1=CC=C(N=C(N2)C3=NNC(=C3)C=3C=CC(NC(=O)NC=4C=C(C=CC=4)C#N)=CC=3)C2=C1 NIROGIQQTUAATM-UHFFFAOYSA-N 0.000 claims description 2
- GXQVYPBKQQFZJF-UHFFFAOYSA-N 1-(3-fluorophenyl)-3-[4-[5-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-3-yl]phenyl]urea Chemical compound C1CN(C)CCN1C1=CC=C(NC(=N2)C3=NNC(=C3)C=3C=CC(NC(=O)NC=4C=C(F)C=CC=4)=CC=3)C2=C1 GXQVYPBKQQFZJF-UHFFFAOYSA-N 0.000 claims description 2
- YYZZMSASVOGZPR-UHFFFAOYSA-N 1-(3-methoxyphenyl)-3-[4-[5-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-3-yl]phenyl]urea Chemical compound COC1=CC=CC(NC(=O)NC=2C=CC(=CC=2)C=2NN=C(C=2)C=2NC3=CC=C(C=C3N=2)N2CCN(C)CC2)=C1 YYZZMSASVOGZPR-UHFFFAOYSA-N 0.000 claims description 2
- XVVRZPFJWNSBJM-UHFFFAOYSA-N 1-(4-chlorophenyl)-3-[4-[5-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-3-yl]phenyl]urea Chemical compound C1CN(C)CCN1C1=CC=C(NC(=N2)C3=NNC(=C3)C=3C=CC(NC(=O)NC=4C=CC(Cl)=CC=4)=CC=3)C2=C1 XVVRZPFJWNSBJM-UHFFFAOYSA-N 0.000 claims description 2
- USWNGWLNYFSMOU-UHFFFAOYSA-N 1-(4-fluorophenyl)-3-[4-[5-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-3-yl]phenyl]urea Chemical compound C1CN(C)CCN1C1=CC=C(NC(=N2)C3=NNC(=C3)C=3C=CC(NC(=O)NC=4C=CC(F)=CC=4)=CC=3)C2=C1 USWNGWLNYFSMOU-UHFFFAOYSA-N 0.000 claims description 2
- YEINNCXXMOKBBJ-UHFFFAOYSA-N 1-(5-chloro-2-methoxyphenyl)-3-[4-[3-[4-(4-methylpiperazin-1-yl)phenyl]-1h-pyrazol-5-yl]phenyl]urea Chemical compound COC1=CC=C(Cl)C=C1NC(=O)NC1=CC=C(C2=NNC(=C2)C=2C=CC(=CC=2)N2CCN(C)CC2)C=C1 YEINNCXXMOKBBJ-UHFFFAOYSA-N 0.000 claims description 2
- QMXYXDDXLLYOEK-UHFFFAOYSA-N 1-(5-fluoro-2-methylphenyl)-3-[4-[3-[4-(4-methylpiperazin-1-yl)phenyl]-1h-pyrazol-5-yl]phenyl]urea Chemical compound C1CN(C)CCN1C1=CC=C(C=2NN=C(C=2)C=2C=CC(NC(=O)NC=3C(=CC=C(F)C=3)C)=CC=2)C=C1 QMXYXDDXLLYOEK-UHFFFAOYSA-N 0.000 claims description 2
- ZKECLIPXXHRCLL-UHFFFAOYSA-N 1-[3,5-bis(trifluoromethyl)phenyl]-3-[4-[5-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-3-yl]phenyl]urea Chemical compound C1CN(C)CCN1C1=CC=C(NC(=N2)C3=NNC(=C3)C=3C=CC(NC(=O)NC=4C=C(C=C(C=4)C(F)(F)F)C(F)(F)F)=CC=3)C2=C1 ZKECLIPXXHRCLL-UHFFFAOYSA-N 0.000 claims description 2
- BFAZLLILGUBKLN-UHFFFAOYSA-N 1-[4-[3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl]phenyl]-3-(4-phenoxyphenyl)urea Chemical compound C1CN(C)CCN1C1=CC=C(NC(=N2)C3=NNC(=C3)C=3C=CC(NC(=O)NC=4C=CC(OC=5C=CC=CC=5)=CC=4)=CC=3)C2=C1 BFAZLLILGUBKLN-UHFFFAOYSA-N 0.000 claims description 2
- HFATULJQXYRWAW-UHFFFAOYSA-N 1-[4-[5-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-3-yl]phenyl]-3-[3-(trifluoromethyl)phenyl]urea Chemical compound C1CN(C)CCN1C1=CC=C(NC(=N2)C3=NNC(=C3)C=3C=CC(NC(=O)NC=4C=C(C=CC=4)C(F)(F)F)=CC=3)C2=C1 HFATULJQXYRWAW-UHFFFAOYSA-N 0.000 claims description 2
- BJEFIVOIKYMRCJ-UHFFFAOYSA-N 1-[4-[5-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-3-yl]phenyl]-3-[4-(trifluoromethyl)phenyl]urea Chemical compound C1CN(C)CCN1C1=CC=C(N=C(N2)C3=NNC(=C3)C=3C=CC(NC(=O)NC=4C=CC(=CC=4)C(F)(F)F)=CC=3)C2=C1 BJEFIVOIKYMRCJ-UHFFFAOYSA-N 0.000 claims description 2
- VLCFKYAYJHYTIF-UHFFFAOYSA-N 1-[4-[5-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-3-yl]phenyl]-3-phenylurea Chemical compound C1CN(C)CCN1C1=CC=C(NC(=N2)C3=NNC(=C3)C=3C=CC(NC(=O)NC=4C=CC=CC=4)=CC=3)C2=C1 VLCFKYAYJHYTIF-UHFFFAOYSA-N 0.000 claims description 2
- WXOCBNPLVCJMTC-UHFFFAOYSA-N 1-[4-chloro-3-(trifluoromethyl)phenyl]-3-[4-[3-[3-(4-methylpiperazin-1-yl)phenyl]-1h-pyrazol-5-yl]phenyl]urea Chemical compound C1CN(C)CCN1C1=CC=CC(C2=NNC(=C2)C=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 WXOCBNPLVCJMTC-UHFFFAOYSA-N 0.000 claims description 2
- JAVCFRVUAWLRTC-UHFFFAOYSA-N 1-[4-chloro-3-(trifluoromethyl)phenyl]-3-[4-[3-[4-(4-methylpiperazin-1-yl)phenyl]-1h-pyrazol-5-yl]phenyl]urea Chemical compound C1CN(C)CCN1C1=CC=C(C2=NNC(=C2)C=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)C=C1 JAVCFRVUAWLRTC-UHFFFAOYSA-N 0.000 claims description 2
- NCTVANRJURGURM-UHFFFAOYSA-N 1-[4-fluoro-3-(trifluoromethyl)phenyl]-3-[4-[5-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-3-yl]phenyl]urea Chemical compound C1CN(C)CCN1C1=CC=C(NC(=N2)C3=NNC(=C3)C=3C=CC(NC(=O)NC=4C=C(C(F)=CC=4)C(F)(F)F)=CC=3)C2=C1 NCTVANRJURGURM-UHFFFAOYSA-N 0.000 claims description 2
- BWMOTGRGZOGGPC-DAFODLJHSA-N 4-[(E)-2-(3-pyridin-4-yl-1H-pyrazol-5-yl)ethenyl]phenol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(C=2C=CN=CC=2)=NN1 BWMOTGRGZOGGPC-DAFODLJHSA-N 0.000 claims description 2
- NBLSOXLPSOZWOF-ORCRQEGFSA-N 4-[(E)-2-[3-(5-chloro-1-benzofuran-2-yl)-1H-pyrazol-5-yl]ethenyl]phenol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(C=2OC3=CC=C(Cl)C=C3C=2)=NN1 NBLSOXLPSOZWOF-ORCRQEGFSA-N 0.000 claims description 2
- YIKSCQDJHCMVMK-UHFFFAOYSA-N Oxamide Chemical compound NC(=O)C(N)=O YIKSCQDJHCMVMK-UHFFFAOYSA-N 0.000 claims description 2
- 208000027866 inflammatory disease Diseases 0.000 claims description 2
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims 2
- SEXTZSJGAYFEEI-UHFFFAOYSA-N 1-(3-ethylphenyl)-3-[4-[5-[6-(4-ethylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-3-yl]phenyl]urea Chemical compound C1CN(CC)CCN1C1=CC=C(NC(=N2)C3=NNC(=C3)C=3C=CC(NC(=O)NC=4C=C(CC)C=CC=4)=CC=3)C2=C1 SEXTZSJGAYFEEI-UHFFFAOYSA-N 0.000 claims 1
- KSRNSBDVOGXRSA-UHFFFAOYSA-N 1-[4-[3-[4-(4-methylpiperazin-1-yl)phenyl]-1h-pyrazol-5-yl]phenyl]-3-(4-phenoxyphenyl)urea Chemical compound C1CN(C)CCN1C1=CC=C(C=2NN=C(C=2)C=2C=CC(NC(=O)NC=3C=CC(OC=4C=CC=CC=4)=CC=3)=CC=2)C=C1 KSRNSBDVOGXRSA-UHFFFAOYSA-N 0.000 claims 1
- RWFMPPFJSSCFSZ-UHFFFAOYSA-N 1-[4-[5-[6-(4-ethylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-3-yl]phenyl]-3-[3-(trifluoromethyl)phenyl]urea Chemical compound C1CN(CC)CCN1C1=CC=C(NC(=N2)C3=NNC(=C3)C=3C=CC(NC(=O)NC=4C=C(C=CC=4)C(F)(F)F)=CC=3)C2=C1 RWFMPPFJSSCFSZ-UHFFFAOYSA-N 0.000 claims 1
- DKKVMPVQHSMJDF-UHFFFAOYSA-N 1-[4-chloro-3-(trifluoromethyl)phenyl]-3-[4-[5-[6-(4-ethylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-3-yl]phenyl]urea Chemical compound C1CN(CC)CCN1C1=CC=C(NC(=N2)C3=NNC(=C3)C=3C=CC(NC(=O)NC=4C=C(C(Cl)=CC=4)C(F)(F)F)=CC=3)C2=C1 DKKVMPVQHSMJDF-UHFFFAOYSA-N 0.000 claims 1
- XULCFTJVFFDUEQ-UHFFFAOYSA-N 1-tert-butyl-3-[4-[5-[6-(4-ethylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-3-yl]phenyl]urea Chemical compound C1CN(CC)CCN1C1=CC=C(NC(=N2)C3=NNC(=C3)C=3C=CC(NC(=O)NC(C)(C)C)=CC=3)C2=C1 XULCFTJVFFDUEQ-UHFFFAOYSA-N 0.000 claims 1
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 69
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
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- Emergency Medicine (AREA)
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- Neurosurgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Dermatology (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Investigating Or Analysing Biological Materials (AREA)
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| US61068904P | 2004-09-17 | 2004-09-17 | |
| US60/610,689 | 2004-09-17 | ||
| PCT/US2005/032839 WO2006033943A2 (en) | 2004-09-17 | 2005-09-15 | Pyrazole kinase modulators and methods of use |
Related Child Applications (1)
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| JP2012112312A Division JP2012153720A (ja) | 2004-09-17 | 2012-05-16 | ピラゾールキナーゼモジュレーターおよび使用方法 |
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| EP (1) | EP1797072A4 (enExample) |
| JP (2) | JP5063351B2 (enExample) |
| AU (1) | AU2005287170B2 (enExample) |
| CA (1) | CA2579313A1 (enExample) |
| WO (1) | WO2006033943A2 (enExample) |
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| AR051093A1 (es) | 2004-09-20 | 2006-12-20 | Xenon Pharmaceuticals Inc | Derivados heterociclicos y su uso como inhibidores de estearoil-coa desaturasa |
| MX2007003332A (es) | 2004-09-20 | 2007-06-05 | Xenon Pharmaceuticals Inc | Derivados heterociclicos y su uso como inhibidores de estearoil-coa-desaturasa. |
| EP2029138A1 (en) | 2005-06-03 | 2009-03-04 | Xenon Pharmaceuticals Inc. | Aminothiazole derivatives as human stearoyl-coa desaturase inhibitors |
| CN101058561B (zh) * | 2006-04-19 | 2011-01-26 | 苏州爱斯鹏药物研发有限责任公司 | 用于抑制蛋白激酶的二苯脲衍生物及其组合物和用途 |
| WO2009143039A2 (en) * | 2008-05-19 | 2009-11-26 | Schering Corporation | Heterocyclic compounds as factor ixa inhibitors |
| ES2620027T3 (es) | 2008-09-03 | 2017-06-27 | Biomarin Pharmaceutical Inc. | Composiciones que incluyen derivados del ácido 6-aminohexanoico como inhibidores de HDAC |
| US8329757B2 (en) * | 2008-10-14 | 2012-12-11 | Charlesson, Llc | Curcumin analog compositions and related methods |
| EP2545046A4 (en) | 2010-03-11 | 2015-03-25 | Sumitomo Dainippon Pharma Co Ltd | CYCLIC N-ACYL-AMINE DERIVATIVE OR PHARMACEUTICALLY ALLOWED SALT THEREOF |
| KR20130089232A (ko) * | 2010-06-15 | 2013-08-09 | 바이엘 인텔렉쳐 프로퍼티 게엠베하 | 안트라닐산 디아미드 유도체 |
| US9540395B2 (en) | 2011-02-28 | 2017-01-10 | Biomarin Pharmaceutical Inc. | Histone deacetylase inhibitors |
| US10059723B2 (en) | 2011-02-28 | 2018-08-28 | Biomarin Pharmaceutical Inc. | Histone deacetylase inhibitors |
| US8957066B2 (en) | 2011-02-28 | 2015-02-17 | Biomarin Pharmaceutical Inc. | Histone deacetylase inhibitors |
| CA2832650C (en) | 2011-04-11 | 2019-05-07 | Pharma Eight Co. Ltd. | Pyrazole derivative |
| US9199975B2 (en) | 2011-09-30 | 2015-12-01 | Asana Biosciences, Llc | Biaryl imidazole derivatives for regulating CYP17 |
| US8809372B2 (en) | 2011-09-30 | 2014-08-19 | Asana Biosciences, Llc | Pyridine derivatives |
| RU2682679C2 (ru) * | 2012-10-10 | 2019-03-20 | Грин Тек Ко., Лтд. | Новые производные пиразола |
| PL403149A1 (pl) * | 2013-03-14 | 2014-09-15 | Celon Pharma Spółka Akcyjna | Nowe związki pochodne pirazolilobenzo[d]imidazolu |
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| EP2944635B1 (en) * | 2014-05-15 | 2018-11-28 | Council of Scientific & Industrial Research | Pyrazole linked benzimidazole conjugates and a process for preparation thereof |
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- 2005-09-15 WO PCT/US2005/032839 patent/WO2006033943A2/en not_active Ceased
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- 2005-09-15 EP EP05796701A patent/EP1797072A4/en not_active Withdrawn
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| WO2006033943A3 (en) | 2006-06-01 |
| US20070293507A1 (en) | 2007-12-20 |
| AU2005287170A1 (en) | 2006-03-30 |
| AU2005287170B2 (en) | 2012-03-29 |
| EP1797072A4 (en) | 2009-09-09 |
| EP1797072A2 (en) | 2007-06-20 |
| WO2006033943A2 (en) | 2006-03-30 |
| JP2012153720A (ja) | 2012-08-16 |
| JP2008513464A (ja) | 2008-05-01 |
| US8710038B2 (en) | 2014-04-29 |
| CA2579313A1 (en) | 2006-03-30 |
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