CA2738383A1 - Bicyclic amides as kinase inhibitors - Google Patents
Bicyclic amides as kinase inhibitors Download PDFInfo
- Publication number
- CA2738383A1 CA2738383A1 CA2738383A CA2738383A CA2738383A1 CA 2738383 A1 CA2738383 A1 CA 2738383A1 CA 2738383 A CA2738383 A CA 2738383A CA 2738383 A CA2738383 A CA 2738383A CA 2738383 A1 CA2738383 A1 CA 2738383A1
- Authority
- CA
- Canada
- Prior art keywords
- carboxylic acid
- yloxy
- amide
- pyrimidin
- trifluoromethyl
- 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
- -1 Bicyclic amides Chemical class 0.000 title description 80
- 229940043355 kinase inhibitor Drugs 0.000 title description 5
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 349
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 62
- 201000010099 disease Diseases 0.000 claims abstract description 54
- 238000011282 treatment Methods 0.000 claims abstract description 35
- 102000001253 Protein Kinase Human genes 0.000 claims abstract description 31
- 108060006633 protein kinase Proteins 0.000 claims abstract description 31
- 230000001419 dependent effect Effects 0.000 claims abstract description 29
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 15
- 238000002360 preparation method Methods 0.000 claims abstract description 15
- 230000002062 proliferating effect Effects 0.000 claims abstract description 12
- 241001465754 Metazoa Species 0.000 claims abstract description 10
- 150000003839 salts Chemical class 0.000 claims description 56
- VFTMUBRDBGFXFE-UHFFFAOYSA-N 6-(2-aminopyrimidin-4-yl)oxynaphthalene-1-carboxylic acid Chemical compound NC1=NC=CC(OC=2C=C3C=CC=C(C3=CC=2)C(O)=O)=N1 VFTMUBRDBGFXFE-UHFFFAOYSA-N 0.000 claims description 12
- WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 claims description 10
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 7
- 108091008606 PDGF receptors Proteins 0.000 claims description 7
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 claims description 7
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 claims description 7
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 6
- TWFFJHRNKDBJDO-UHFFFAOYSA-N 6-(6-acetamidopyrimidin-4-yl)oxy-n-[4-(piperazin-1-ylmethyl)-3-(trifluoromethyl)phenyl]naphthalene-1-carboxamide Chemical group C1=NC(NC(=O)C)=CC(OC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C(CN3CCNCC3)=CC=2)C(F)(F)F)=N1 TWFFJHRNKDBJDO-UHFFFAOYSA-N 0.000 claims description 5
- HSCHEEFSTGEALA-UHFFFAOYSA-N ethyl 6-[5-[[3-(trifluoromethyl)phenyl]carbamoyl]naphthalen-2-yl]oxypyrimidine-4-carboxylate Chemical compound C1=NC(C(=O)OCC)=CC(OC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=N1 HSCHEEFSTGEALA-UHFFFAOYSA-N 0.000 claims description 5
- FZPKNHBWJOADAF-UHFFFAOYSA-N 6-(6-aminopyrimidin-4-yl)sulfanyl-n-[3-(trifluoromethyl)phenyl]naphthalene-1-carboxamide Chemical compound C1=NC(N)=CC(SC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=N1 FZPKNHBWJOADAF-UHFFFAOYSA-N 0.000 claims description 4
- IRMRHQFPMZOYEI-UHFFFAOYSA-N 6-(6-chloropyrimidin-4-yl)oxy-n-[3-(trifluoromethyl)phenyl]naphthalene-1-carboxamide Chemical compound FC(F)(F)C1=CC=CC(NC(=O)C=2C3=CC=C(OC=4N=CN=C(Cl)C=4)C=C3C=CC=2)=C1 IRMRHQFPMZOYEI-UHFFFAOYSA-N 0.000 claims description 4
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- FJRWUJVJRLYUAE-UHFFFAOYSA-N 6-(2-amino-6-chloropyrimidin-4-yl)oxy-n-[3-(trifluoromethyl)phenyl]-2h-1,3-benzoxazole-3-carboxamide Chemical compound NC1=NC(Cl)=CC(OC=2C=C3OCN(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=N1 FJRWUJVJRLYUAE-UHFFFAOYSA-N 0.000 claims description 3
- SCJAEBIZFYREML-UHFFFAOYSA-N 6-(2-aminopyridin-4-yl)oxy-n-[3-(trifluoromethyl)phenyl]naphthalene-1-carboxamide Chemical compound C1=NC(N)=CC(OC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=C1 SCJAEBIZFYREML-UHFFFAOYSA-N 0.000 claims description 3
- MLLQJNIKDWEEFT-UHFFFAOYSA-N 6-(2-aminopyrimidin-4-yl)oxy-n-[3-(trifluoromethyl)phenyl]naphthalene-1-carboxamide Chemical compound NC1=NC=CC(OC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=N1 MLLQJNIKDWEEFT-UHFFFAOYSA-N 0.000 claims description 3
- WIYISPHQCCAUQX-UHFFFAOYSA-N 6-[2-(6-aminopyrimidin-4-yl)ethynyl]-n-[3-(trifluoromethyl)phenyl]naphthalene-1-carboxamide Chemical compound C1=NC(N)=CC(C#CC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=N1 WIYISPHQCCAUQX-UHFFFAOYSA-N 0.000 claims description 3
- HBDAFVSEKQEJER-UHFFFAOYSA-N 6-[5-[[3-(trifluoromethyl)phenyl]carbamoyl]naphthalen-2-yl]oxypyrimidine-4-carboxylic acid Chemical compound C1=NC(C(=O)O)=CC(OC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=N1 HBDAFVSEKQEJER-UHFFFAOYSA-N 0.000 claims description 3
- AJDRIMZLXGDHJE-UHFFFAOYSA-N 6-[6-(aminomethyl)pyrimidin-4-yl]oxy-n-[3-(trifluoromethyl)phenyl]naphthalene-1-carboxamide Chemical compound C1=NC(CN)=CC(OC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=N1 AJDRIMZLXGDHJE-UHFFFAOYSA-N 0.000 claims description 3
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 3
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- YWQHGSISKQLGOL-UHFFFAOYSA-N 5-(2-amino-6-chloropyrimidin-4-yl)oxy-4-fluoro-2-methyl-n-[3-(trifluoromethyl)phenyl]-2,3-dihydroindole-1-carboxamide Chemical compound C=1C=CC(C(F)(F)F)=CC=1NC(=O)N1C(C)CC(C=2F)=C1C=CC=2OC1=CC(Cl)=NC(N)=N1 YWQHGSISKQLGOL-UHFFFAOYSA-N 0.000 claims description 2
- LLHGBNDJYPXHPX-UHFFFAOYSA-N 5-(6-chloropyrimidin-4-yl)oxy-n-[3-(trifluoromethyl)phenyl]indole-1-carboxamide Chemical compound FC(F)(F)C1=CC=CC(NC(=O)N2C3=CC=C(OC=4N=CN=C(Cl)C=4)C=C3C=C2)=C1 LLHGBNDJYPXHPX-UHFFFAOYSA-N 0.000 claims description 2
- ZSSLWIKFWYEAID-UHFFFAOYSA-N 6-(2-acetamidopyrimidin-4-yl)oxy-n-[3-(trifluoromethyl)phenyl]naphthalene-1-carboxamide Chemical compound CC(=O)NC1=NC=CC(OC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=N1 ZSSLWIKFWYEAID-UHFFFAOYSA-N 0.000 claims description 2
- LVCPXLQPUCRFEF-UHFFFAOYSA-N 6-(2-amino-6-chloropyrimidin-4-yl)oxy-n-[3-(trifluoromethyl)phenyl]naphthalene-1-carboxamide Chemical compound NC1=NC(Cl)=CC(OC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=N1 LVCPXLQPUCRFEF-UHFFFAOYSA-N 0.000 claims description 2
- NVGZXCBMFHERPE-UHFFFAOYSA-N 6-(2-amino-6-chloropyrimidin-4-yl)oxy-n-[4-chloro-3-(trifluoromethyl)phenyl]naphthalene-1-carboxamide Chemical compound NC1=NC(Cl)=CC(OC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C(Cl)=CC=2)C(F)(F)F)=N1 NVGZXCBMFHERPE-UHFFFAOYSA-N 0.000 claims description 2
- NKCHVSIUCFMOCK-UHFFFAOYSA-N 6-(2-amino-6-chloropyrimidin-4-yl)oxy-n-[4-fluoro-3-(trifluoromethyl)phenyl]-2h-1,3-benzoxazole-3-carboxamide Chemical compound NC1=NC(Cl)=CC(OC=2C=C3OCN(C3=CC=2)C(=O)NC=2C=C(C(F)=CC=2)C(F)(F)F)=N1 NKCHVSIUCFMOCK-UHFFFAOYSA-N 0.000 claims description 2
- AFGQCILTWDDJGX-UHFFFAOYSA-N 6-(2-aminopyrimidin-4-yl)oxy-n-[2-(trifluoromethyl)pyridin-4-yl]naphthalene-1-carboxamide Chemical compound NC1=NC=CC(OC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(N=CC=2)C(F)(F)F)=N1 AFGQCILTWDDJGX-UHFFFAOYSA-N 0.000 claims description 2
- BQLMDRWSAXTQDP-UHFFFAOYSA-N 6-(2-aminopyrimidin-4-yl)oxy-n-[3-(trifluoromethyl)phenyl]-2h-1,3-benzoxazole-3-carboxamide Chemical compound NC1=NC=CC(OC=2C=C3OCN(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=N1 BQLMDRWSAXTQDP-UHFFFAOYSA-N 0.000 claims description 2
- JUMSOKFYADZQBG-UHFFFAOYSA-N 6-(2-aminopyrimidin-4-yl)oxy-n-[4-chloro-3-(trifluoromethyl)phenyl]naphthalene-1-carboxamide Chemical compound NC1=NC=CC(OC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C(Cl)=CC=2)C(F)(F)F)=N1 JUMSOKFYADZQBG-UHFFFAOYSA-N 0.000 claims description 2
- UABWKKXAYFPRLN-UHFFFAOYSA-N 6-(2-aminopyrimidin-4-yl)oxy-n-[4-methyl-3-(trifluoromethyl)phenyl]naphthalene-1-carboxamide Chemical compound C1=C(C(F)(F)F)C(C)=CC=C1NC(=O)C1=CC=CC2=CC(OC=3N=C(N)N=CC=3)=CC=C12 UABWKKXAYFPRLN-UHFFFAOYSA-N 0.000 claims description 2
- ZJCINOVJQXANNT-UHFFFAOYSA-N 6-(2-methylpyridin-4-yl)oxy-n-[3-(trifluoromethyl)phenyl]naphthalene-1-carboxamide Chemical compound C1=NC(C)=CC(OC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=C1 ZJCINOVJQXANNT-UHFFFAOYSA-N 0.000 claims description 2
- VLZUUIPXPCMYBS-UHFFFAOYSA-N 6-(6-acetamidopyrimidin-4-yl)oxy-n-[4-[(4-propan-2-ylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]naphthalene-1-carboxamide Chemical group C1CN(C(C)C)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)C1=CC=CC2=CC(OC=3N=CN=C(NC(C)=O)C=3)=CC=C12 VLZUUIPXPCMYBS-UHFFFAOYSA-N 0.000 claims description 2
- WNUFDOATFVDKDL-UHFFFAOYSA-N 6-(6-aminopyrimidin-4-yl)oxy-1-ethyl-n-[4-fluoro-3-(trifluoromethyl)phenyl]indole-3-carboxamide Chemical group C12=CC=C(OC=3N=CN=C(N)C=3)C=C2N(CC)C=C1C(=O)NC1=CC=C(F)C(C(F)(F)F)=C1 WNUFDOATFVDKDL-UHFFFAOYSA-N 0.000 claims description 2
- OZVGFORICFITBM-UHFFFAOYSA-N 6-(6-aminopyrimidin-4-yl)oxy-1-propan-2-yl-n-[3-(trifluoromethyl)phenyl]indole-3-carboxamide Chemical group C12=CC=C(OC=3N=CN=C(N)C=3)C=C2N(C(C)C)C=C1C(=O)NC1=CC=CC(C(F)(F)F)=C1 OZVGFORICFITBM-UHFFFAOYSA-N 0.000 claims description 2
- VPTISLWBZVDVEQ-UHFFFAOYSA-N 6-(6-aminopyrimidin-4-yl)oxy-n-(3-cyclopropyl-4-fluorophenyl)naphthalene-1-carboxamide Chemical compound C1=NC(N)=CC(OC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C(F)=CC=2)C2CC2)=N1 VPTISLWBZVDVEQ-UHFFFAOYSA-N 0.000 claims description 2
- FQFHVPBPMZFVJQ-UHFFFAOYSA-N 6-(6-aminopyrimidin-4-yl)oxy-n-(3-methoxyphenyl)-1h-indole-3-carboxamide Chemical compound COC1=CC=CC(NC(=O)C=2C3=CC=C(OC=4N=CN=C(N)C=4)C=C3NC=2)=C1 FQFHVPBPMZFVJQ-UHFFFAOYSA-N 0.000 claims description 2
- FNEJOLWLMOCTPG-UHFFFAOYSA-N 6-(6-aminopyrimidin-4-yl)oxy-n-[3-(trifluoromethyl)phenyl]-1h-indole-3-carboxamide Chemical compound C1=NC(N)=CC(OC=2C=C3NC=C(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=N1 FNEJOLWLMOCTPG-UHFFFAOYSA-N 0.000 claims description 2
- IOYGAWXBNPFOKF-UHFFFAOYSA-N 6-(6-aminopyrimidin-4-yl)oxy-n-[3-(trifluoromethyl)phenyl]naphthalene-1-carboxamide Chemical compound C1=NC(N)=CC(OC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=N1 IOYGAWXBNPFOKF-UHFFFAOYSA-N 0.000 claims description 2
- JUOKOZJZJFOBRU-UHFFFAOYSA-N 6-(6-aminopyrimidin-4-yl)oxy-n-[4-fluoro-3-(trifluoromethyl)phenyl]-2h-1,3-benzoxazole-3-carboxamide Chemical compound C1=NC(N)=CC(OC=2C=C3OCN(C3=CC=2)C(=O)NC=2C=C(C(F)=CC=2)C(F)(F)F)=N1 JUOKOZJZJFOBRU-UHFFFAOYSA-N 0.000 claims description 2
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- QZXLKDMWSGVVKN-UHFFFAOYSA-N 6-(6-chloropyrimidin-4-yl)oxy-n-[4-fluoro-3-(trifluoromethyl)phenyl]-2h-1,3-benzoxazole-3-carboxamide Chemical compound C1=C(C(F)(F)F)C(F)=CC=C1NC(=O)N1C2=CC=C(OC=3N=CN=C(Cl)C=3)C=C2OC1 QZXLKDMWSGVVKN-UHFFFAOYSA-N 0.000 claims description 2
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- NLJGYOWLAWTHSL-UHFFFAOYSA-N 5-(6-aminopyrimidin-4-yl)oxy-n-[3-(trifluoromethyl)phenyl]indole-1-carboxamide Chemical compound C1=NC(N)=CC(OC=2C=C3C=CN(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=N1 NLJGYOWLAWTHSL-UHFFFAOYSA-N 0.000 claims 1
- VJWNWZULYRZHBE-UHFFFAOYSA-N 6-(2-aminopyrimidin-4-yl)oxy-n-[3,4-bis(trifluoromethyl)phenyl]naphthalene-1-carboxamide Chemical compound NC1=NC=CC(OC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C(=CC=2)C(F)(F)F)C(F)(F)F)=N1 VJWNWZULYRZHBE-UHFFFAOYSA-N 0.000 claims 1
- BBRGUKCRMBODJV-UHFFFAOYSA-N 6-(2-aminopyrimidin-4-yl)oxy-n-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]naphthalene-1-carboxamide Chemical compound C1CN(C)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)C1=CC=CC2=CC(OC=3N=C(N)N=CC=3)=CC=C12 BBRGUKCRMBODJV-UHFFFAOYSA-N 0.000 claims 1
- OFVHAJGZGXBLSR-UHFFFAOYSA-N 6-(2-aminopyrimidin-4-yl)oxy-n-[4-fluoro-3-(trifluoromethyl)phenyl]-2h-1,3-benzoxazole-3-carboxamide Chemical compound NC1=NC=CC(OC=2C=C3OCN(C3=CC=2)C(=O)NC=2C=C(C(F)=CC=2)C(F)(F)F)=N1 OFVHAJGZGXBLSR-UHFFFAOYSA-N 0.000 claims 1
- DLMNCLOTSVZOQM-UHFFFAOYSA-N 6-(2-aminopyrimidin-4-yl)oxy-n-[4-morpholin-4-yl-3-(trifluoromethyl)phenyl]naphthalene-1-carboxamide Chemical compound NC1=NC=CC(OC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C(N3CCOCC3)=CC=2)C(F)(F)F)=N1 DLMNCLOTSVZOQM-UHFFFAOYSA-N 0.000 claims 1
- MZZJNOOADWVFPD-UHFFFAOYSA-N 6-(6-acetamidopyrimidin-4-yl)oxy-n-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]naphthalene-1-carboxamide Chemical group C1CN(C)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)C1=CC=CC2=CC(OC=3N=CN=C(NC(C)=O)C=3)=CC=C12 MZZJNOOADWVFPD-UHFFFAOYSA-N 0.000 claims 1
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- SKTMLPGTEVKBIR-UHFFFAOYSA-N 6-(6-aminopyrimidin-4-yl)oxy-1-methyl-n-[3-(trifluoromethyl)phenyl]indole-3-carboxamide Chemical group C12=CC=C(OC=3N=CN=C(N)C=3)C=C2N(C)C=C1C(=O)NC1=CC=CC(C(F)(F)F)=C1 SKTMLPGTEVKBIR-UHFFFAOYSA-N 0.000 claims 1
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- MUJOHKZRVOONTJ-UHFFFAOYSA-N 6-(6-aminopyrimidin-4-yl)oxy-n-[4-(piperazin-1-ylmethyl)-3-(trifluoromethyl)phenyl]naphthalene-1-carboxamide Chemical group C1=NC(N)=CC(OC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C(CN3CCNCC3)=CC=2)C(F)(F)F)=N1 MUJOHKZRVOONTJ-UHFFFAOYSA-N 0.000 claims 1
- QNQMRPJYANIZFU-UHFFFAOYSA-N 6-(6-aminopyrimidin-4-yl)oxy-n-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]naphthalene-1-carboxamide Chemical group C1CN(C)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)C1=CC=CC2=CC(OC=3N=CN=C(N)C=3)=CC=C12 QNQMRPJYANIZFU-UHFFFAOYSA-N 0.000 claims 1
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- ABPASPQYTUBWPC-UHFFFAOYSA-N 6-(6-aminopyrimidin-4-yl)oxy-n-[4-fluoro-3-(trifluoromethyl)phenyl]-1h-indole-3-carboxamide Chemical compound C1=NC(N)=CC(OC=2C=C3NC=C(C3=CC=2)C(=O)NC=2C=C(C(F)=CC=2)C(F)(F)F)=N1 ABPASPQYTUBWPC-UHFFFAOYSA-N 0.000 claims 1
- HJFDTNBKNJFDQP-UHFFFAOYSA-N 6-(6-aminopyrimidin-4-yl)oxy-n-[4-fluoro-3-(trifluoromethyl)phenyl]naphthalene-1-carboxamide Chemical compound C1=NC(N)=CC(OC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C(F)=CC=2)C(F)(F)F)=N1 HJFDTNBKNJFDQP-UHFFFAOYSA-N 0.000 claims 1
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- SEDPQAOIKPOVQF-UHFFFAOYSA-N 6-(6-aminopyrimidin-4-yl)sulfinyl-n-[3-(trifluoromethyl)phenyl]naphthalene-1-carboxamide Chemical compound C1=NC(N)=CC(S(=O)C=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=N1 SEDPQAOIKPOVQF-UHFFFAOYSA-N 0.000 claims 1
- KIOXMRDEVOZGDM-UHFFFAOYSA-N 6-(6-aminopyrimidin-4-yl)sulfonyl-n-[3-(trifluoromethyl)phenyl]naphthalene-1-carboxamide Chemical compound C1=NC(N)=CC(S(=O)(=O)C=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=N1 KIOXMRDEVOZGDM-UHFFFAOYSA-N 0.000 claims 1
- WAYFISOBGVQDMY-UHFFFAOYSA-N 6-[2-(2-aminopyrimidin-4-yl)ethyl]-n-[3-(trifluoromethyl)phenyl]naphthalene-1-carboxamide Chemical compound NC1=NC=CC(CCC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=N1 WAYFISOBGVQDMY-UHFFFAOYSA-N 0.000 claims 1
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- GQLJRGLQCOSRFU-UHFFFAOYSA-N 6-[6-(methylaminomethyl)pyrimidin-4-yl]oxy-n-[3-(trifluoromethyl)phenyl]naphthalene-1-carboxamide Chemical compound C1=NC(CNC)=CC(OC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=N1 GQLJRGLQCOSRFU-UHFFFAOYSA-N 0.000 claims 1
- CJUNRDGLRNNPMQ-UHFFFAOYSA-N 7-(2-acetamidopyrimidin-4-yl)oxy-n-[4-methyl-3-(trifluoromethyl)phenyl]-2,3-dihydro-1,4-benzoxazine-4-carboxamide Chemical compound CC(=O)NC1=NC=CC(OC=2C=C3OCCN(C3=CC=2)C(=O)NC=2C=C(C(C)=CC=2)C(F)(F)F)=N1 CJUNRDGLRNNPMQ-UHFFFAOYSA-N 0.000 claims 1
- YWCAIELAUCRENJ-UHFFFAOYSA-N 7-(2-aminopyrimidin-4-yl)oxy-n-[3-(trifluoromethyl)phenyl]-2,3-dihydro-1,4-benzoxazine-4-carboxamide Chemical compound NC1=NC=CC(OC=2C=C3OCCN(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=N1 YWCAIELAUCRENJ-UHFFFAOYSA-N 0.000 claims 1
- MWDJKTIMNCEXHY-UHFFFAOYSA-N 7-(2-aminopyrimidin-4-yl)oxy-n-[4-(morpholin-4-ylmethyl)-3-(trifluoromethyl)phenyl]-2,3-dihydro-1,4-benzoxazine-4-carboxamide Chemical compound NC1=NC=CC(OC=2C=C3OCCN(C3=CC=2)C(=O)NC=2C=C(C(CN3CCOCC3)=CC=2)C(F)(F)F)=N1 MWDJKTIMNCEXHY-UHFFFAOYSA-N 0.000 claims 1
- YXNGFQINBJJRED-UHFFFAOYSA-N 7-(2-aminopyrimidin-4-yl)oxy-n-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-2,3-dihydro-1,4-benzoxazine-4-carboxamide Chemical compound C1CN(C)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)N1C2=CC=C(OC=3N=C(N)N=CC=3)C=C2OCC1 YXNGFQINBJJRED-UHFFFAOYSA-N 0.000 claims 1
- VNTVZWPYYGACJH-UHFFFAOYSA-N 7-(6-aminopyrimidin-4-yl)oxy-n-[3-(trifluoromethyl)phenyl]-2,3-dihydro-1,4-benzoxazine-4-carboxamide Chemical compound C1=NC(N)=CC(OC=2C=C3OCCN(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=N1 VNTVZWPYYGACJH-UHFFFAOYSA-N 0.000 claims 1
- MZNXOUPPFSBLDL-UHFFFAOYSA-N 7-(6-aminopyrimidin-4-yl)oxy-n-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]isoquinoline-4-carboxamide Chemical group C1CN(C)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)C1=CN=CC2=CC(OC=3N=CN=C(N)C=3)=CC=C12 MZNXOUPPFSBLDL-UHFFFAOYSA-N 0.000 claims 1
- PDGHYHHYWKGENG-UHFFFAOYSA-N 7-(6-aminopyrimidin-4-yl)oxy-n-[4-fluoro-3-(trifluoromethyl)phenyl]-2,3-dihydro-1,4-benzoxazine-4-carboxamide Chemical compound C1=NC(N)=CC(OC=2C=C3OCCN(C3=CC=2)C(=O)NC=2C=C(C(F)=CC=2)C(F)(F)F)=N1 PDGHYHHYWKGENG-UHFFFAOYSA-N 0.000 claims 1
- MNVCSIRQZGIVFJ-UHFFFAOYSA-N 7-(6-aminopyrimidin-4-yl)oxy-n-[4-methyl-3-(trifluoromethyl)phenyl]-2,3-dihydro-1,4-benzoxazine-4-carboxamide Chemical compound C1=C(C(F)(F)F)C(C)=CC=C1NC(=O)N1C2=CC=C(OC=3N=CN=C(N)C=3)C=C2OCC1 MNVCSIRQZGIVFJ-UHFFFAOYSA-N 0.000 claims 1
- HJNHNYQGZINXCZ-UHFFFAOYSA-N 7-(6-aminopyrimidin-4-yl)oxy-n-[5-tert-butyl-2-(4-fluorophenyl)pyrazol-3-yl]isoquinoline-4-carboxamide Chemical group C=1C=C(F)C=CC=1N1N=C(C(C)(C)C)C=C1NC(=O)C(C1=CC=2)=CN=CC1=CC=2OC1=CC(N)=NC=N1 HJNHNYQGZINXCZ-UHFFFAOYSA-N 0.000 claims 1
- LVUMBGTXGBVQDQ-UHFFFAOYSA-N 7-(6-aminopyrimidin-4-yl)oxy-n-[5-tert-butyl-2-(4-propan-2-ylphenyl)pyrazol-3-yl]isoquinoline-4-carboxamide Chemical group C1=CC(C(C)C)=CC=C1N1C(NC(=O)C=2C3=CC=C(OC=4N=CN=C(N)C=4)C=C3C=NC=2)=CC(C(C)(C)C)=N1 LVUMBGTXGBVQDQ-UHFFFAOYSA-N 0.000 claims 1
- NLKLQCVVFMMLOQ-UHFFFAOYSA-N 7-[6-(methylamino)pyrimidin-4-yl]oxy-n-[3-(trifluoromethyl)phenyl]-2,3-dihydro-1,4-benzoxazine-4-carboxamide Chemical compound C1=NC(NC)=CC(OC=2C=C3OCCN(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=N1 NLKLQCVVFMMLOQ-UHFFFAOYSA-N 0.000 claims 1
- UYAMUQBTPCZVEC-UHFFFAOYSA-N 7-[6-(methylamino)pyrimidin-4-yl]oxy-n-[3-(trifluoromethyl)phenyl]isoquinoline-4-carboxamide Chemical group C1=NC(NC)=CC(OC=2C=C3C=NC=C(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=N1 UYAMUQBTPCZVEC-UHFFFAOYSA-N 0.000 claims 1
- YXSQAIRCGUCESM-UHFFFAOYSA-N 7-[6-(methylamino)pyrimidin-4-yl]oxy-n-[4-methyl-3-(trifluoromethyl)phenyl]-2,3-dihydro-1,4-benzoxazine-4-carboxamide Chemical compound C1=NC(NC)=CC(OC=2C=C3OCCN(C3=CC=2)C(=O)NC=2C=C(C(C)=CC=2)C(F)(F)F)=N1 YXSQAIRCGUCESM-UHFFFAOYSA-N 0.000 claims 1
- 206010064930 age-related macular degeneration Diseases 0.000 claims 1
- 208000002780 macular degeneration Diseases 0.000 claims 1
- BUDKGDSKCODTPK-UHFFFAOYSA-N methyl n-[4-[5-[[3-(trifluoromethyl)phenyl]carbamoyl]naphthalen-2-yl]oxypyridin-2-yl]carbamate Chemical compound C1=NC(NC(=O)OC)=CC(OC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=C1 BUDKGDSKCODTPK-UHFFFAOYSA-N 0.000 claims 1
- XRVKNCPPEZPTNN-UHFFFAOYSA-N methyl n-[4-[[4-[[4-methyl-3-(trifluoromethyl)phenyl]carbamoyl]-2,3-dihydro-1,4-benzoxazin-7-yl]oxy]pyrimidin-2-yl]carbamate Chemical compound COC(=O)NC1=NC=CC(OC=2C=C3OCCN(C3=CC=2)C(=O)NC=2C=C(C(C)=CC=2)C(F)(F)F)=N1 XRVKNCPPEZPTNN-UHFFFAOYSA-N 0.000 claims 1
- MQUWQZHUNVDYNQ-UHFFFAOYSA-N methyl n-[6-[4-[[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]carbamoyl]isoquinolin-7-yl]oxypyrimidin-4-yl]carbamate Chemical group C1=NC(NC(=O)OC)=CC(OC=2C=C3C=NC=C(C3=CC=2)C(=O)NC=2C=C(C(CN3CCN(C)CC3)=CC=2)C(F)(F)F)=N1 MQUWQZHUNVDYNQ-UHFFFAOYSA-N 0.000 claims 1
- PDVMOWFZIQXCRV-UHFFFAOYSA-N methyl n-[6-[5-[[4-(piperazin-1-ylmethyl)-3-(trifluoromethyl)phenyl]carbamoyl]naphthalen-2-yl]oxypyrimidin-4-yl]carbamate Chemical group C1=NC(NC(=O)OC)=CC(OC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C(CN3CCNCC3)=CC=2)C(F)(F)F)=N1 PDVMOWFZIQXCRV-UHFFFAOYSA-N 0.000 claims 1
- FDNKIUUODNILFM-UHFFFAOYSA-N methyl n-[6-[5-[[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]carbamoyl]naphthalen-2-yl]oxypyrimidin-4-yl]carbamate Chemical group C1=NC(NC(=O)OC)=CC(OC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C(CN3CCN(C)CC3)=CC=2)C(F)(F)F)=N1 FDNKIUUODNILFM-UHFFFAOYSA-N 0.000 claims 1
- AWWQCMOJLLTAAT-UHFFFAOYSA-N methyl n-[6-[5-[[4-[(4-propan-2-ylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]carbamoyl]naphthalen-2-yl]oxypyrimidin-4-yl]carbamate Chemical group C1=NC(NC(=O)OC)=CC(OC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C(CN3CCN(CC3)C(C)C)=CC=2)C(F)(F)F)=N1 AWWQCMOJLLTAAT-UHFFFAOYSA-N 0.000 claims 1
- BFGIVBLNSZCLCP-UHFFFAOYSA-N methyl n-[[6-[5-[[3-(trifluoromethyl)phenyl]carbamoyl]naphthalen-2-yl]oxypyrimidin-4-yl]methyl]carbamate Chemical compound C1=NC(CNC(=O)OC)=CC(OC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=N1 BFGIVBLNSZCLCP-UHFFFAOYSA-N 0.000 claims 1
- MVGDSKXMPFUOBM-UHFFFAOYSA-N n,n-dimethyl-6-[5-[[3-(trifluoromethyl)phenyl]carbamoyl]naphthalen-2-yl]oxypyrimidine-4-carboxamide Chemical compound C1=NC(C(=O)N(C)C)=CC(OC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=N1 MVGDSKXMPFUOBM-UHFFFAOYSA-N 0.000 claims 1
- OOSLATSNZMUTDX-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-4-[5-[[3-(trifluoromethyl)phenyl]carbamoyl]naphthalen-2-yl]oxypyridine-2-carboxamide Chemical compound C1=NC(C(=O)NCCN(C)C)=CC(OC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=C1 OOSLATSNZMUTDX-UHFFFAOYSA-N 0.000 claims 1
- JDLBMRZCFBHXPN-UHFFFAOYSA-N n-[4-fluoro-3-(trifluoromethyl)phenyl]-6-(pyridin-4-ylmethyl)naphthalene-1-carboxamide Chemical compound C1=C(C(F)(F)F)C(F)=CC=C1NC(=O)C1=CC=CC2=CC(CC=3C=CN=CC=3)=CC=C12 JDLBMRZCFBHXPN-UHFFFAOYSA-N 0.000 claims 1
- AXZZPASEFPVKDR-UHFFFAOYSA-N n-[5-tert-butyl-2-(3-methylphenyl)pyrazol-3-yl]-6-[6-(methylamino)pyrimidin-4-yl]oxynaphthalene-1-carboxamide Chemical compound C1=NC(NC)=CC(OC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2N(N=C(C=2)C(C)(C)C)C=2C=C(C)C=CC=2)=N1 AXZZPASEFPVKDR-UHFFFAOYSA-N 0.000 claims 1
- QHYBBRWWHGPYMO-UHFFFAOYSA-N n-[5-tert-butyl-2-[3-(dimethylcarbamoyl)phenyl]pyrazol-3-yl]-6-[6-(methylamino)pyrimidin-4-yl]oxynaphthalene-1-carboxamide Chemical compound C1=NC(NC)=CC(OC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2N(N=C(C=2)C(C)(C)C)C=2C=C(C=CC=2)C(=O)N(C)C)=N1 QHYBBRWWHGPYMO-UHFFFAOYSA-N 0.000 claims 1
- PJBZAESZQNRXOI-UHFFFAOYSA-N n-[5-tert-butyl-2-[3-(morpholin-4-ylmethyl)phenyl]pyrazol-3-yl]-6-[6-(methylamino)pyrimidin-4-yl]oxynaphthalene-1-carboxamide Chemical compound C1=NC(NC)=CC(OC=2C=C3C=CC=C(C3=CC=2)C(=O)NC=2N(N=C(C=2)C(C)(C)C)C=2C=C(CN3CCOCC3)C=CC=2)=N1 PJBZAESZQNRXOI-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
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- C07—ORGANIC CHEMISTRY
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- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
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Landscapes
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| GB0511687A GB0511687D0 (en) | 2005-06-08 | 2005-06-08 | Organic compounds |
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| CA2574829A CA2574829C (en) | 2004-09-15 | 2005-09-14 | Bicyclic amides as kinase inhibitors |
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| CA2574829A Division CA2574829C (en) | 2004-09-15 | 2005-09-14 | Bicyclic amides as kinase inhibitors |
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| CA2574829A Expired - Fee Related CA2574829C (en) | 2004-09-15 | 2005-09-14 | Bicyclic amides as kinase inhibitors |
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| PE20060664A1 (es) | 2004-09-15 | 2006-08-04 | Novartis Ag | Amidas biciclicas como inhibidores de cinasa |
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| ES2400375T3 (es) | 2006-04-07 | 2013-04-09 | Novartis Ag | Combinación que comprende A) un compuesto de pirimidilaminobenzamida y B)un inhibidor de cinasa THR315LLE |
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| US8846704B2 (en) | 2007-01-31 | 2014-09-30 | YM Biosciences Austraila Pty Ltd | Thiopyrimidine-based compounds and uses thereof |
| CA2683049A1 (en) | 2007-04-17 | 2008-10-23 | Novartis Ag | Organic compounds |
| WO2008132505A1 (en) * | 2007-04-27 | 2008-11-06 | Astrazeneca Ab | N' - (phenyl) -n- (morpholin-4-yl-pyridin-2-yl) -pyrimidine-2, 4-diamine derivatives as ephb4 kinase inhibitors for the treatment of proliferative conditions |
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