MX2012002317A - Compuestos de urea que contienen heteroarilo 5,6-biciclicos como inhibidores de cinasa. - Google Patents

Info

Publication number

MX2012002317A

MX2012002317A MX2012002317A MX2012002317A MX2012002317A MX 2012002317 A MX2012002317 A MX 2012002317A MX 2012002317 A MX2012002317 A MX 2012002317A MX 2012002317 A MX2012002317 A MX 2012002317A MX 2012002317 A MX2012002317 A MX 2012002317A

Authority

MX

Mexico

Prior art keywords

pyrrolo

urea

pyridin

ylmethyl

indol

Prior art date

2009-08-24

Links

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• 150000003672 ureas Chemical class 0.000 title abstract 2
• 229940043355 kinase inhibitor Drugs 0.000 title description 3
• 239000003757 phosphotransferase inhibitor Substances 0.000 title description 3
• -1 CSFlR Proteins 0.000 claims abstract description 924
• 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 claims abstract description 32
• 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 claims abstract description 29
• 102000001253 Protein Kinase Human genes 0.000 claims abstract description 16
• 108060006633 protein kinase Proteins 0.000 claims abstract description 16
• 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 claims abstract description 12
• 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 claims abstract description 12
• 102100030340 Ephrin type-A receptor 2 Human genes 0.000 claims abstract description 7
• 230000001404 mediated effect Effects 0.000 claims abstract description 7
• 108010055196 EphA2 Receptor Proteins 0.000 claims abstract description 6
• XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 663
• 239000004202 carbamide Substances 0.000 claims description 622
• 150000001875 compounds Chemical class 0.000 claims description 162
• 206010028980 Neoplasm Diseases 0.000 claims description 45
• 125000000217 alkyl group Chemical group 0.000 claims description 31
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 27
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 25
• 125000003118 aryl group Chemical group 0.000 claims description 25
• JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 25
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 24
• 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 22
• 125000001072 heteroaryl group Chemical group 0.000 claims description 22
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 21
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 21
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 21
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 21
• 238000000034 method Methods 0.000 claims description 21
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 20
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 18
• 229910052757 nitrogen Inorganic materials 0.000 claims description 18
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
• 125000003342 alkenyl group Chemical group 0.000 claims description 17
• 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 claims description 16
• 229910052740 iodine Inorganic materials 0.000 claims description 16
• 125000000304 alkynyl group Chemical group 0.000 claims description 15
• 125000005843 halogen group Chemical group 0.000 claims description 15
• 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 14
• 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 14
• 125000002947 alkylene group Chemical group 0.000 claims description 14
• 150000003839 salts Chemical class 0.000 claims description 14
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 13
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
• 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 12
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 12
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 11
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 11
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 11
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
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• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 10
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 9
• SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 8
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 8
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 8
• 125000004043 oxo group Chemical group O=* 0.000 claims description 8
• 229910052760 oxygen Inorganic materials 0.000 claims description 8
• 229920006395 saturated elastomer Polymers 0.000 claims description 8
• 229910052717 sulfur Inorganic materials 0.000 claims description 8
• 229910052720 vanadium Inorganic materials 0.000 claims description 8
• 229910052770 Uranium Inorganic materials 0.000 claims description 6
• 239000005441 aurora Substances 0.000 claims description 6
• 125000005842 heteroatom Chemical group 0.000 claims description 6
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 6
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• 201000004681 Psoriasis Diseases 0.000 claims description 5
• 125000003545 alkoxy group Chemical group 0.000 claims description 5
• 125000002541 furyl group Chemical group 0.000 claims description 5
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 5
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 4
• 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims description 4
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• YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims description 4
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
• 229910052727 yttrium Inorganic materials 0.000 claims description 4
• 208000023275 Autoimmune disease Diseases 0.000 claims description 3
• ZEOWTGPWHLSLOG-UHFFFAOYSA-N Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F Chemical compound Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F ZEOWTGPWHLSLOG-UHFFFAOYSA-N 0.000 claims description 3
• 101150029707 ERBB2 gene Proteins 0.000 claims description 3
• 101710182386 Fibroblast growth factor receptor 1 Proteins 0.000 claims description 3
• 102100023593 Fibroblast growth factor receptor 1 Human genes 0.000 claims description 3
• 101710182389 Fibroblast growth factor receptor 2 Proteins 0.000 claims description 3
• 102100023600 Fibroblast growth factor receptor 2 Human genes 0.000 claims description 3
• 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 claims description 3
• 102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 claims description 3
• 102100027844 Fibroblast growth factor receptor 4 Human genes 0.000 claims description 3
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• 102100028198 Macrophage colony-stimulating factor 1 receptor Human genes 0.000 claims description 3
• 101100268648 Mus musculus Abl1 gene Proteins 0.000 claims description 3
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• 206010038910 Retinitis Diseases 0.000 claims description 3
• 208000038016 acute inflammation Diseases 0.000 claims description 3
• 230000006022 acute inflammation Effects 0.000 claims description 3
• 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 claims description 3
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 3
• 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
• 206010012601 diabetes mellitus Diseases 0.000 claims description 3
• 125000001153 fluoro group Chemical group F* 0.000 claims description 3
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 3
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 3
• 125000002883 imidazolyl group Chemical group 0.000 claims description 3
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 3
• 125000001041 indolyl group Chemical group 0.000 claims description 3
• 125000001624 naphthyl group Chemical group 0.000 claims description 3
• 201000008383 nephritis Diseases 0.000 claims description 3
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
• 125000002971 oxazolyl group Chemical group 0.000 claims description 3
• 125000004076 pyridyl group Chemical group 0.000 claims description 3
• 125000000335 thiazolyl group Chemical group 0.000 claims description 3
• 125000001544 thienyl group Chemical group 0.000 claims description 3
• FBIWFINTOBOZJS-UHFFFAOYSA-N 1-(2,5-dimethoxyphenyl)-3-[1-(1h-pyrrolo[2,3-b]pyridin-3-ylmethyl)indol-4-yl]urea Chemical compound COC1=CC=C(OC)C(NC(=O)NC=2C=3C=CN(CC=4C5=CC=CN=C5NC=4)C=3C=CC=2)=C1 FBIWFINTOBOZJS-UHFFFAOYSA-N 0.000 claims description 2
• HFHFGHLXUCOHLN-UHFFFAOYSA-N 2-fluorophenol Chemical compound OC1=CC=CC=C1F HFHFGHLXUCOHLN-UHFFFAOYSA-N 0.000 claims description 2
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