AU2013303922A1 - Pyrazolyl-ureas as kinase inhibitors - Google Patents
Pyrazolyl-ureas as kinase inhibitors Download PDFInfo
- Publication number
- AU2013303922A1 AU2013303922A1 AU2013303922A AU2013303922A AU2013303922A1 AU 2013303922 A1 AU2013303922 A1 AU 2013303922A1 AU 2013303922 A AU2013303922 A AU 2013303922A AU 2013303922 A AU2013303922 A AU 2013303922A AU 2013303922 A1 AU2013303922 A1 AU 2013303922A1
- Authority
- AU
- Australia
- Prior art keywords
- amino
- pyrimidin
- pyrazol
- oxy
- naphthalen
- 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
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- 229940043355 kinase inhibitor Drugs 0.000 title description 4
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 293
- 238000000034 method Methods 0.000 claims description 183
- 239000000203 mixture Substances 0.000 claims description 175
- 125000000217 alkyl group Chemical group 0.000 claims description 135
- -1 4-((4-(3-(3-(tert-butyl)-1-(4-(dimethylamino)phenyl)-1 H-pyrazol-5-yl)ureido) naphthalen- 1 -yl)oxy)pyrimidin-2-yl Chemical group 0.000 claims description 100
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 73
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 65
- 125000000623 heterocyclic group Chemical group 0.000 claims description 64
- 229910052739 hydrogen Inorganic materials 0.000 claims description 64
- 150000003839 salts Chemical class 0.000 claims description 59
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 58
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 54
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 53
- 238000011282 treatment Methods 0.000 claims description 53
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 35
- 229910052757 nitrogen Inorganic materials 0.000 claims description 33
- 125000001424 substituent group Chemical group 0.000 claims description 33
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
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- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
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- VSZGPKBBMSAYNT-RRFJBIMHSA-N oseltamivir Chemical compound CCOC(=O)C1=C[C@@H](OC(CC)CC)[C@H](NC(C)=O)[C@@H](N)C1 VSZGPKBBMSAYNT-RRFJBIMHSA-N 0.000 claims description 5
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- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
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- DDKIKSYBXRUQAD-UHFFFAOYSA-N 3-[[6-[4-[[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-4-yl]amino]-5-methoxy-N-(2-morpholin-4-ylethyl)benzamide Chemical compound COC1=CC=C(C=C1)N1N=C(C=C1NC(=O)NC1=C2C=CC=CC2=C(OC2=CC(NC3=CC(=CC(OC)=C3)C(=O)NCCN3CCOCC3)=NC=N2)C=C1)C(C)(C)C DDKIKSYBXRUQAD-UHFFFAOYSA-N 0.000 claims description 3
- HUMIGOFJWQKXPY-UHFFFAOYSA-N 3-methoxy-5-[[4-[4-[[2-(4-methylphenyl)-5-(1,1,2,2,2-pentafluoroethyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-n-(2-morpholin-4-ylethyl)benzamide Chemical compound C=1C(C(=O)NCCN2CCOCC2)=CC(OC)=CC=1NC(N=1)=NC=CC=1OC(C1=CC=CC=C11)=CC=C1NC(=O)NC1=CC(C(F)(F)C(F)(F)F)=NN1C1=CC=C(C)C=C1 HUMIGOFJWQKXPY-UHFFFAOYSA-N 0.000 claims description 3
- BPJALVMFXXJAJS-UHFFFAOYSA-N 3-methoxy-5-[[4-[4-[[2-(6-methoxypyridin-3-yl)-5-propan-2-ylpyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-n-(2-morpholin-4-ylethyl)benzamide Chemical compound C=1C(C(=O)NCCN2CCOCC2)=CC(OC)=CC=1NC(N=1)=NC=CC=1OC(C1=CC=CC=C11)=CC=C1NC(=O)NC1=CC(C(C)C)=NN1C1=CC=C(OC)N=C1 BPJALVMFXXJAJS-UHFFFAOYSA-N 0.000 claims description 3
- QHHCOZDURKDLDL-UHFFFAOYSA-N 3-methoxy-n-(2-methoxyethyl)-5-[[4-[4-[[2-(4-methoxyphenyl)-5-propan-2-ylpyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]benzamide Chemical compound COC1=CC(C(=O)NCCOC)=CC(NC=2N=C(OC=3C4=CC=CC=C4C(NC(=O)NC=4N(N=C(C=4)C(C)C)C=4C=CC(OC)=CC=4)=CC=3)C=CN=2)=C1 QHHCOZDURKDLDL-UHFFFAOYSA-N 0.000 claims description 3
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- XGOUHJLISKQBDN-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-3-methoxy-5-[[4-[4-[[2-(4-methoxyphenyl)-5-propan-2-ylpyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]benzamide Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C3=CC=CC=C3C(OC=3N=C(NC=4C=C(C=C(OC)C=4)C(=O)NCCN(C)C)N=CC=3)=CC=2)=CC(C(C)C)=N1 XGOUHJLISKQBDN-UHFFFAOYSA-N 0.000 claims description 3
- RNGNGIHVGNTTHO-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-3-methoxy-5-[[4-[4-[[2-(4-methylphenyl)-5-propan-2-ylpyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]benzamide Chemical compound CN(C)CCNC(=O)C1=CC(OC)=CC(NC=2N=C(OC=3C4=CC=CC=C4C(NC(=O)NC=4N(N=C(C=4)C(C)C)C=4C=CC(C)=CC=4)=CC=3)C=CN=2)=C1 RNGNGIHVGNTTHO-UHFFFAOYSA-N 0.000 claims description 3
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- KKBSRZBNVASLTJ-UHFFFAOYSA-N 3-[[4-[4-[[5-ethyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-5-methoxy-n-(2-morpholin-4-ylethyl)benzamide Chemical compound C=1C=C(C)C=CC=1N1N=C(CC)C=C1NC(=O)NC(C1=CC=CC=C11)=CC=C1OC(N=1)=CC=NC=1NC(C=1)=CC(OC)=CC=1C(=O)NCCN1CCOCC1 KKBSRZBNVASLTJ-UHFFFAOYSA-N 0.000 claims description 2
- KEYJNCXZEKAAGP-UHFFFAOYSA-N 3-[[4-[4-[[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-5-ethynyl-n-(2-methoxyethyl)benzamide Chemical compound C#CC1=CC(C(=O)NCCOC)=CC(NC=2N=C(OC=3C4=CC=CC=C4C(NC(=O)NC=4N(N=C(C=4)C(C)(C)C)C=4C=CC(OC)=CC=4)=CC=3)C=CN=2)=C1 KEYJNCXZEKAAGP-UHFFFAOYSA-N 0.000 claims description 2
- RIGZTRRKOZWKPG-SANMLTNESA-N 3-[[4-[4-[[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-5-ethynyl-n-[(2s)-1-methoxypropan-2-yl]benzamide Chemical compound C#CC1=CC(C(=O)N[C@@H](C)COC)=CC(NC=2N=C(OC=3C4=CC=CC=C4C(NC(=O)NC=4N(N=C(C=4)C(C)(C)C)C=4C=CC(OC)=CC=4)=CC=3)C=CN=2)=C1 RIGZTRRKOZWKPG-SANMLTNESA-N 0.000 claims description 2
- VXMFHVFTECVHPF-UHFFFAOYSA-N 3-[[4-[4-[[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-5-methoxy-n-(2-morpholin-4-ylethyl)benzamide Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C3=CC=CC=C3C(OC=3N=C(NC=4C=C(C=C(OC)C=4)C(=O)NCCN4CCOCC4)N=CC=3)=CC=2)=CC(C(C)(C)C)=N1 VXMFHVFTECVHPF-UHFFFAOYSA-N 0.000 claims description 2
- VBOWNSNIMAAIIO-UHFFFAOYSA-N 3-[[4-[4-[[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-N-[2-(dimethylamino)ethyl]-4-methoxybenzamide Chemical compound COc1ccc(cc1)-n1nc(cc1NC(=O)Nc1ccc(Oc2ccnc(Nc3cc(ccc3OC)C(=O)NCCN(C)C)n2)c2ccccc12)C(C)(C)C VBOWNSNIMAAIIO-UHFFFAOYSA-N 0.000 claims description 2
- AALWZYBTBKNLKF-UHFFFAOYSA-N 3-[[4-[4-[[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-n-(2-morpholin-4-ylethyl)benzamide Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C3=CC=CC=C3C(OC=3N=C(NC=4C=C(C=CC=4)C(=O)NCCN4CCOCC4)N=CC=3)=CC=2)=CC(C(C)(C)C)=N1 AALWZYBTBKNLKF-UHFFFAOYSA-N 0.000 claims description 2
- JSEJMGKNQGRPEI-UHFFFAOYSA-N 3-[[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-4-methoxy-n-(2-morpholin-4-ylethyl)benzamide Chemical compound COC1=CC=C(C(=O)NCCN2CCOCC2)C=C1NC(N=1)=NC=CC=1OC(C1=CC=CC=C11)=CC=C1NC(=O)NC1=CC(C(C)(C)C)=NN1C1=CC=C(C)C=C1 JSEJMGKNQGRPEI-UHFFFAOYSA-N 0.000 claims description 2
- WMSBTWYNUSSVEZ-UHFFFAOYSA-N 3-[[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-5-ethynyl-n-(2-methyl-1-morpholin-4-ylpropan-2-yl)benzamide Chemical compound C1=CC(C)=CC=C1N1C(NC(=O)NC=2C3=CC=CC=C3C(OC=3N=C(NC=4C=C(C=C(C=4)C#C)C(=O)NC(C)(C)CN4CCOCC4)N=CC=3)=CC=2)=CC(C(C)(C)C)=N1 WMSBTWYNUSSVEZ-UHFFFAOYSA-N 0.000 claims description 2
- VWGMFKBQYRNIIN-PMERELPUSA-N 3-[[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-5-ethynyl-n-[(2s)-1-morpholin-4-ylpropan-2-yl]benzamide Chemical compound C([C@H](C)NC(=O)C=1C=C(C=C(NC=2N=C(OC=3C4=CC=CC=C4C(NC(=O)NC=4N(N=C(C=4)C(C)(C)C)C=4C=CC(C)=CC=4)=CC=3)C=CN=2)C=1)C#C)N1CCOCC1 VWGMFKBQYRNIIN-PMERELPUSA-N 0.000 claims description 2
- KDRIQANXEFIHCL-UHFFFAOYSA-N 3-[[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-5-methoxy-n-(2-methoxyethyl)benzamide Chemical compound COC1=CC(C(=O)NCCOC)=CC(NC=2N=C(OC=3C4=CC=CC=C4C(NC(=O)NC=4N(N=C(C=4)C(C)(C)C)C=4C=CC(C)=CC=4)=CC=3)C=CN=2)=C1 KDRIQANXEFIHCL-UHFFFAOYSA-N 0.000 claims description 2
- OGQDHXGPFCDXGA-UHFFFAOYSA-N 3-[[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-5-methoxy-n-(2-morpholin-4-ylethyl)benzamide Chemical compound C=1C(C(=O)NCCN2CCOCC2)=CC(OC)=CC=1NC(N=1)=NC=CC=1OC(C1=CC=CC=C11)=CC=C1NC(=O)NC1=CC(C(C)(C)C)=NN1C1=CC=C(C)C=C1 OGQDHXGPFCDXGA-UHFFFAOYSA-N 0.000 claims description 2
- URRPWKVYUYOQBW-UHFFFAOYSA-N 3-[[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-5-methylbenzamide Chemical compound C1=CC(C)=CC=C1N1C(NC(=O)NC=2C3=CC=CC=C3C(OC=3N=C(NC=4C=C(C=C(C)C=4)C(N)=O)N=CC=3)=CC=2)=CC(C(C)(C)C)=N1 URRPWKVYUYOQBW-UHFFFAOYSA-N 0.000 claims description 2
- XZCLCFIAUCVNJF-UHFFFAOYSA-N 3-[[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-n,n-dimethylbenzamide Chemical compound CN(C)C(=O)C1=CC=CC(NC=2N=C(OC=3C4=CC=CC=C4C(NC(=O)NC=4N(N=C(C=4)C(C)(C)C)C=4C=CC(C)=CC=4)=CC=3)C=CN=2)=C1 XZCLCFIAUCVNJF-UHFFFAOYSA-N 0.000 claims description 2
- JTERLHICJVJIRK-UHFFFAOYSA-N 3-[[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-n-(2-hydroxyethyl)-4-methoxybenzamide Chemical compound COC1=CC=C(C(=O)NCCO)C=C1NC1=NC=CC(OC=2C3=CC=CC=C3C(NC(=O)NC=3N(N=C(C=3)C(C)(C)C)C=3C=CC(C)=CC=3)=CC=2)=N1 JTERLHICJVJIRK-UHFFFAOYSA-N 0.000 claims description 2
- LHYKFLNJIXCRLM-UHFFFAOYSA-N 3-[[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-n-(2-hydroxyethyl)-5-methoxybenzamide Chemical compound OCCNC(=O)C1=CC(OC)=CC(NC=2N=C(OC=3C4=CC=CC=C4C(NC(=O)NC=4N(N=C(C=4)C(C)(C)C)C=4C=CC(C)=CC=4)=CC=3)C=CN=2)=C1 LHYKFLNJIXCRLM-UHFFFAOYSA-N 0.000 claims description 2
- OCGMYHIDTHTZSV-UHFFFAOYSA-N 3-[[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-n-[2-(dimethylamino)ethyl]-5-methoxybenzamide Chemical compound CN(C)CCNC(=O)C1=CC(OC)=CC(NC=2N=C(OC=3C4=CC=CC=C4C(NC(=O)NC=4N(N=C(C=4)C(C)(C)C)C=4C=CC(C)=CC=4)=CC=3)C=CN=2)=C1 OCGMYHIDTHTZSV-UHFFFAOYSA-N 0.000 claims description 2
- STYBOAPFAFDXGS-UHFFFAOYSA-N 3-[[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-n-[2-(dimethylamino)ethyl]benzamide Chemical compound CN(C)CCNC(=O)C1=CC=CC(NC=2N=C(OC=3C4=CC=CC=C4C(NC(=O)NC=4N(N=C(C=4)C(C)(C)C)C=4C=CC(C)=CC=4)=CC=3)C=CN=2)=C1 STYBOAPFAFDXGS-UHFFFAOYSA-N 0.000 claims description 2
- GHRBLHUQTOTLMU-UHFFFAOYSA-N 3-[[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC(NC=2N=C(OC=3C4=CC=CC=C4C(NC(=O)NC=4N(N=C(C=4)C(C)(C)C)C=4C=CC(C)=CC=4)=CC=3)C=CN=2)=C1 GHRBLHUQTOTLMU-UHFFFAOYSA-N 0.000 claims description 2
- HOBGSWDBYMRRJR-UHFFFAOYSA-N 3-[[4-[4-[[5-tert-butyl-2-(4-methylthiophen-2-yl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-n-(2-morpholin-4-ylethyl)benzamide Chemical compound CC1=CSC(N2C(=CC(=N2)C(C)(C)C)NC(=O)NC=2C3=CC=CC=C3C(OC=3N=C(NC=4C=C(C=CC=4)C(=O)NCCN4CCOCC4)N=CC=3)=CC=2)=C1 HOBGSWDBYMRRJR-UHFFFAOYSA-N 0.000 claims description 2
- GAJUUQYPFUJQCH-UHFFFAOYSA-N 3-[[4-[4-[[5-tert-butyl-2-(6-methoxypyridin-3-yl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-5-ethynyl-n-(2-morpholin-4-ylethyl)benzamide Chemical compound C1=NC(OC)=CC=C1N1C(NC(=O)NC=2C3=CC=CC=C3C(OC=3N=C(NC=4C=C(C=C(C=4)C#C)C(=O)NCCN4CCOCC4)N=CC=3)=CC=2)=CC(C(C)(C)C)=N1 GAJUUQYPFUJQCH-UHFFFAOYSA-N 0.000 claims description 2
- DTYGFXKVLYKJLW-UHFFFAOYSA-N 3-[[4-[4-[[5-tert-butyl-2-(6-methoxypyridin-3-yl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-5-methoxy-n-(2-morpholin-4-ylethyl)benzamide Chemical compound C=1C(C(=O)NCCN2CCOCC2)=CC(OC)=CC=1NC(N=1)=NC=CC=1OC(C1=CC=CC=C11)=CC=C1NC(=O)NC1=CC(C(C)(C)C)=NN1C1=CC=C(OC)N=C1 DTYGFXKVLYKJLW-UHFFFAOYSA-N 0.000 claims description 2
- MTZANZYELGIMJM-UHFFFAOYSA-N 3-[[6-[4-[[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]carbamoylamino]-2,3-dimethylphenoxy]pyrimidin-4-yl]amino]-5-methoxy-n-(2-morpholin-4-ylethyl)benzamide Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C(=C(C)C(OC=3N=CN=C(NC=4C=C(C=C(OC)C=4)C(=O)NCCN4CCOCC4)C=3)=CC=2)C)=CC(C(C)(C)C)=N1 MTZANZYELGIMJM-UHFFFAOYSA-N 0.000 claims description 2
- BZUHVULXCGBRBT-UHFFFAOYSA-N 3-[[6-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-4-yl]amino]-5-methoxy-n-(2-morpholin-4-ylethyl)benzamide Chemical compound C=1C(C(=O)NCCN2CCOCC2)=CC(OC)=CC=1NC(N=CN=1)=CC=1OC(C1=CC=CC=C11)=CC=C1NC(=O)NC1=CC(C(C)(C)C)=NN1C1=CC=C(C)C=C1 BZUHVULXCGBRBT-UHFFFAOYSA-N 0.000 claims description 2
- RQRUNCDCHJDCDE-UHFFFAOYSA-N 3-bromo-5-[[4-[4-[[5-tert-butyl-2-(4-methoxyphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]benzamide Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C3=CC=CC=C3C(OC=3N=C(NC=4C=C(C=C(Br)C=4)C(N)=O)N=CC=3)=CC=2)=CC(C(C)(C)C)=N1 RQRUNCDCHJDCDE-UHFFFAOYSA-N 0.000 claims description 2
- QGRUEQPBBBTRPN-UHFFFAOYSA-N 3-bromo-5-[[4-[4-[[5-tert-butyl-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-n-(2-morpholin-4-ylethyl)benzamide Chemical compound C1=CC(C)=CC=C1N1C(NC(=O)NC=2C3=CC=CC=C3C(OC=3N=C(NC=4C=C(C=C(Br)C=4)C(=O)NCCN4CCOCC4)N=CC=3)=CC=2)=CC(C(C)(C)C)=N1 QGRUEQPBBBTRPN-UHFFFAOYSA-N 0.000 claims description 2
- HSODWQGVXRNOEV-UHFFFAOYSA-N 3-chloro-5-[[4-[4-[[2-(4-methoxyphenyl)-5-propan-2-ylpyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-n-(2-morpholin-4-ylethyl)benzamide Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C3=CC=CC=C3C(OC=3N=C(NC=4C=C(C=C(Cl)C=4)C(=O)NCCN4CCOCC4)N=CC=3)=CC=2)=CC(C(C)C)=N1 HSODWQGVXRNOEV-UHFFFAOYSA-N 0.000 claims description 2
- BRMHQJDIOQPLGE-UHFFFAOYSA-N 3-ethynyl-5-[[4-[4-[[2-(4-methylphenyl)-5-(1,1,2,2,2-pentafluoroethyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-n-(2-morpholin-4-ylethyl)benzamide Chemical compound C1=CC(C)=CC=C1N1C(NC(=O)NC=2C3=CC=CC=C3C(OC=3N=C(NC=4C=C(C=C(C=4)C#C)C(=O)NCCN4CCOCC4)N=CC=3)=CC=2)=CC(C(F)(F)C(F)(F)F)=N1 BRMHQJDIOQPLGE-UHFFFAOYSA-N 0.000 claims description 2
- CSZJFFGJPPIFRZ-UHFFFAOYSA-N 3-ethynyl-5-[[4-[4-[[5-(2-isocyanopropan-2-yl)-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-N-(2-morpholin-4-ylethyl)benzamide Chemical compound Cc1ccc(cc1)-n1nc(cc1NC(=O)Nc1ccc(Oc2ccnc(Nc3cc(cc(c3)C(=O)NCCN3CCOCC3)C#C)n2)c2ccccc12)C(C)(C)[N+]#[C-] CSZJFFGJPPIFRZ-UHFFFAOYSA-N 0.000 claims description 2
- VWAABWZZSWELIA-UHFFFAOYSA-N 3-ethynyl-5-[[4-[4-[[5-(2-methoxypropan-2-yl)-2-(4-methylphenyl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-n-(2-morpholin-4-ylethyl)benzamide Chemical compound C=1C=C(C)C=CC=1N1N=C(C(C)(C)OC)C=C1NC(=O)NC(C1=CC=CC=C11)=CC=C1OC(N=1)=CC=NC=1NC(C=1)=CC(C#C)=CC=1C(=O)NCCN1CCOCC1 VWAABWZZSWELIA-UHFFFAOYSA-N 0.000 claims description 2
- PEDMIJDFAWDUDE-UHFFFAOYSA-N 3-methoxy-4-[[4-[4-[[2-(4-methoxyphenyl)-5-propan-2-ylpyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-n-(2-morpholin-4-ylethyl)benzamide Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C3=CC=CC=C3C(OC=3N=C(NC=4C(=CC(=CC=4)C(=O)NCCN4CCOCC4)OC)N=CC=3)=CC=2)=CC(C(C)C)=N1 PEDMIJDFAWDUDE-UHFFFAOYSA-N 0.000 claims description 2
- PHYNOASHTRVCHA-UHFFFAOYSA-N 3-methoxy-5-[[4-[4-[[2-(4-methoxyphenyl)-5-(oxolan-2-yl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-n-(2-morpholin-4-ylethyl)benzamide Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C3=CC=CC=C3C(OC=3N=C(NC=4C=C(C=C(OC)C=4)C(=O)NCCN4CCOCC4)N=CC=3)=CC=2)=CC(C2OCCC2)=N1 PHYNOASHTRVCHA-UHFFFAOYSA-N 0.000 claims description 2
- IYRPCWRKUVTLQK-UHFFFAOYSA-N 3-methoxy-5-[[4-[4-[[2-(4-methoxyphenyl)-5-(oxolan-3-yl)pyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-n-(2-morpholin-4-ylethyl)benzamide Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C3=CC=CC=C3C(OC=3N=C(NC=4C=C(C=C(OC)C=4)C(=O)NCCN4CCOCC4)N=CC=3)=CC=2)=CC(C2COCC2)=N1 IYRPCWRKUVTLQK-UHFFFAOYSA-N 0.000 claims description 2
- URPHWXWGWHZRLT-UHFFFAOYSA-N 3-methoxy-5-[[4-[4-[[2-(4-methoxyphenyl)-5-prop-1-en-2-ylpyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-n-(2-morpholin-4-ylethyl)benzamide Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C3=CC=CC=C3C(OC=3N=C(NC=4C=C(C=C(OC)C=4)C(=O)NCCN4CCOCC4)N=CC=3)=CC=2)=CC(C(C)=C)=N1 URPHWXWGWHZRLT-UHFFFAOYSA-N 0.000 claims description 2
- BZPKVUCAGBEWOQ-UHFFFAOYSA-N 3-methoxy-5-[[4-[4-[[2-(4-methoxyphenyl)-5-propan-2-ylpyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyridin-2-yl]amino]-n-(2-morpholin-4-ylethyl)benzamide Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C3=CC=CC=C3C(OC=3C=C(NC=4C=C(C=C(OC)C=4)C(=O)NCCN4CCOCC4)N=CC=3)=CC=2)=CC(C(C)C)=N1 BZPKVUCAGBEWOQ-UHFFFAOYSA-N 0.000 claims description 2
- USUSRWRXNKNUGL-UHFFFAOYSA-N 3-methoxy-5-[[4-[4-[[2-(4-methoxyphenyl)-5-propan-2-ylpyrazol-3-yl]carbamoylamino]naphthalen-1-yl]oxypyrimidin-2-yl]amino]-n-(2-morpholin-4-ylethyl)benzamide Chemical compound C1=CC(OC)=CC=C1N1C(NC(=O)NC=2C3=CC=CC=C3C(OC=3N=C(NC=4C=C(C=C(OC)C=4)C(=O)NCCN4CCOCC4)N=CC=3)=CC=2)=CC(C(C)C)=N1 USUSRWRXNKNUGL-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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Landscapes
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| CN101945869B (zh) | 2007-12-19 | 2014-06-18 | 癌症研究技术有限公司 | 吡啶并[2,3-b]吡嗪-8-取代化合物及其用途 |
| US8815896B2 (en) | 2010-02-01 | 2014-08-26 | The Institute Of Cancer Research: Royal Cancer Hospital | 1-(5-tert-butyl-2-phenyl-2H-pyrazol-3-yl)-3-[2-fluoro-4-(1-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-B]pyridin-7-yloxy)-phenyl]-urea and related compounds and their use in therapy |
| EP2578582A1 (en) | 2011-10-03 | 2013-04-10 | Respivert Limited | 1-Pyrazolyl-3-(4-((2-anilinopyrimidin-4-yl)oxy)napththalen-1-yl)ureas as p38 MAP kinase inhibitors |
| PE20142355A1 (es) | 2011-10-03 | 2015-01-10 | Respivert Ltd | 1-pirazolil-3-(4-((2-anilinopirimidin-4-il)oxi)naftalen-1-il)ureas como inhibidores de proteinas cinasas activadas por mitogeno p38 |
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| EA030483B1 (ru) | 2013-04-02 | 2018-08-31 | Респайверт Лимитед | Производные мочевины, полезные в качестве ингибиторов киназы |
| WO2014162121A1 (en) * | 2013-04-02 | 2014-10-09 | Topivert Pharma Limited | Kinase inhibitors based upon n-alkyl pyrazoles |
| GB201320729D0 (en) | 2013-11-25 | 2014-01-08 | Cancer Rec Tech Ltd | Therapeutic compounds and their use |
| GB201320732D0 (en) | 2013-11-25 | 2014-01-08 | Cancer Rec Tech Ltd | Methods of chemical synthesis |
| EP3083604A1 (en) | 2013-12-20 | 2016-10-26 | Respivert Limited | Urea derivatives useful as kinase inhibitors |
| PT3357919T (pt) | 2014-02-14 | 2020-02-20 | Respivert Ltd | Compostos heterocíclicos aromáticos como compostos antiinflamatórios |
| MA40774A (fr) | 2014-10-01 | 2017-08-08 | Respivert Ltd | Dérivés de diaryle-urée en tant qu'inhibiteurs de kinase p38 |
| EP4566638A3 (en) * | 2015-05-29 | 2025-08-27 | Allergan, Inc. | Implant for treatment of an ocular condition |
| MX380907B (es) * | 2015-12-16 | 2025-03-12 | Loxo Oncology Inc | Compuestos útiles como inhibidores de cinasa. |
| MA44607A (fr) | 2016-04-06 | 2021-05-19 | Oxular Acquisitions Ltd | Inhibiteurs de kinase |
| CN109906075A (zh) * | 2016-04-29 | 2019-06-18 | 恩瑟拉德斯医药有限公司 | 用于在发炎病灶或区域中局部注射的脂质体皮质类固醇 |
| CN106771117B (zh) * | 2016-11-25 | 2018-09-14 | 王婧 | 一种中性粒细胞抗原底片的制备方法 |
| US10342786B2 (en) | 2017-10-05 | 2019-07-09 | Fulcrum Therapeutics, Inc. | P38 kinase inhibitors reduce DUX4 and downstream gene expression for the treatment of FSHD |
| CA3078232A1 (en) | 2017-10-05 | 2019-04-11 | Fulcrum Therapeutics, Inc. | Use of p38 inhibitors to reduce expression of dux4 |
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| US6492529B1 (en) | 2000-01-18 | 2002-12-10 | Boehringer Ingelheim Pharmaceuticals, Inc. | Bis pyrazole-1H-pyrazole intermediates and their synthesis |
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| JP2004530690A (ja) | 2001-05-16 | 2004-10-07 | ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド | 抗炎症性薬剤として有用なジアリールウレア誘導体 |
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2012
- 2012-08-17 GB GBGB1214750.0A patent/GB201214750D0/en not_active Ceased
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2013
- 2013-08-16 WO PCT/GB2013/052184 patent/WO2014027209A1/en not_active Ceased
- 2013-08-16 US US14/422,158 patent/US9701670B2/en not_active Expired - Fee Related
- 2013-08-16 JP JP2015527028A patent/JP2015524837A/ja active Pending
- 2013-08-16 EA EA201590391A patent/EA025393B1/ru not_active IP Right Cessation
- 2013-08-16 BR BR112015003218A patent/BR112015003218A2/pt not_active IP Right Cessation
- 2013-08-16 EP EP13750934.5A patent/EP2885284B1/en active Active
- 2013-08-16 AU AU2013303922A patent/AU2013303922A1/en not_active Abandoned
- 2013-08-16 CN CN201380054166.5A patent/CN105073725A/zh active Pending
- 2013-08-16 US US13/969,328 patent/US20140057915A1/en not_active Abandoned
- 2013-08-16 CA CA2881914A patent/CA2881914A1/en not_active Abandoned
- 2013-08-16 MX MX2015002044A patent/MX2015002044A/es unknown
- 2013-08-16 KR KR1020157006554A patent/KR20150056777A/ko not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| GB201214750D0 (en) | 2012-10-03 |
| KR20150056777A (ko) | 2015-05-27 |
| CA2881914A1 (en) | 2014-02-20 |
| BR112015003218A2 (pt) | 2019-09-24 |
| MX2015002044A (es) | 2016-01-22 |
| US9701670B2 (en) | 2017-07-11 |
| EA025393B1 (ru) | 2016-12-30 |
| EP2885284A1 (en) | 2015-06-24 |
| US20140057915A1 (en) | 2014-02-27 |
| US20150218137A1 (en) | 2015-08-06 |
| JP2015524837A (ja) | 2015-08-27 |
| WO2014027209A1 (en) | 2014-02-20 |
| CN105073725A (zh) | 2015-11-18 |
| EA201590391A1 (ru) | 2015-06-30 |
| EP2885284B1 (en) | 2016-11-02 |
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