KR101400905B1 - 신규한 피리도피라진 및 키나제의 조절제로서의 이의 용도 - Google Patents
신규한 피리도피라진 및 키나제의 조절제로서의 이의 용도 Download PDFInfo
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- KR101400905B1 KR101400905B1 KR1020087014068A KR20087014068A KR101400905B1 KR 101400905 B1 KR101400905 B1 KR 101400905B1 KR 1020087014068 A KR1020087014068 A KR 1020087014068A KR 20087014068 A KR20087014068 A KR 20087014068A KR 101400905 B1 KR101400905 B1 KR 101400905B1
- Authority
- KR
- South Korea
- Prior art keywords
- alkyl
- heterocyclyl
- heteroaryl
- group
- aryl
- Prior art date
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- YEYHFKBVNARCNE-UHFFFAOYSA-N pyrido[2,3-b]pyrazine Chemical class N1=CC=NC2=CC=CN=C21 YEYHFKBVNARCNE-UHFFFAOYSA-N 0.000 title claims abstract description 31
- 108091000080 Phosphotransferase Proteins 0.000 title description 25
- 102000020233 phosphotransferase Human genes 0.000 title description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 15
- 238000011282 treatment Methods 0.000 claims abstract description 12
- 201000011510 cancer Diseases 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 852
- 125000000623 heterocyclic group Chemical group 0.000 claims description 606
- 125000001424 substituent group Chemical group 0.000 claims description 480
- 125000003118 aryl group Chemical group 0.000 claims description 446
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 443
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 433
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 425
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 408
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 392
- 125000001072 heteroaryl group Chemical group 0.000 claims description 388
- 229910052739 hydrogen Inorganic materials 0.000 claims description 227
- 229910052794 bromium Inorganic materials 0.000 claims description 171
- 239000000460 chlorine Substances 0.000 claims description 171
- 229910052801 chlorine Inorganic materials 0.000 claims description 171
- 229910052731 fluorine Inorganic materials 0.000 claims description 171
- 229910052740 iodine Inorganic materials 0.000 claims description 171
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 167
- -1 cyclic radicals Chemical class 0.000 claims description 160
- 150000003254 radicals Chemical class 0.000 claims description 95
- 239000001257 hydrogen Substances 0.000 claims description 78
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 71
- 238000006467 substitution reaction Methods 0.000 claims description 34
- 150000001875 compounds Chemical class 0.000 claims description 26
- 206010028980 Neoplasm Diseases 0.000 claims description 21
- 125000003107 substituted aryl group Chemical group 0.000 claims description 20
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 17
- 239000004202 carbamide Substances 0.000 claims description 17
- 208000035475 disorder Diseases 0.000 claims description 16
- 108091007960 PI3Ks Proteins 0.000 claims description 15
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 11
- 101150018665 MAPK3 gene Proteins 0.000 claims description 8
- 102000004190 Enzymes Human genes 0.000 claims description 7
- 108090000790 Enzymes Proteins 0.000 claims description 7
- 150000002431 hydrogen Chemical class 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 229910052717 sulfur Chemical group 0.000 claims description 7
- 125000004122 cyclic group Chemical group 0.000 claims description 6
- 101150024075 Mapk1 gene Proteins 0.000 claims description 5
- 102100036056 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform Human genes 0.000 claims description 5
- 101710204747 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform Proteins 0.000 claims description 5
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 4
- 102100038332 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Human genes 0.000 claims description 4
- 101710093328 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Proteins 0.000 claims description 4
- 102100036052 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform Human genes 0.000 claims description 4
- 101710096503 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform Proteins 0.000 claims description 4
- 101000721642 Homo sapiens Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha Proteins 0.000 claims description 3
- 101000721645 Homo sapiens Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta Proteins 0.000 claims description 3
- 229910019142 PO4 Inorganic materials 0.000 claims description 3
- 102100025058 Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha Human genes 0.000 claims description 3
- 102100025059 Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta Human genes 0.000 claims description 3
- 208000027866 inflammatory disease Diseases 0.000 claims description 3
- 201000001441 melanoma Diseases 0.000 claims description 3
- UHBGYFCCKRAEHA-UHFFFAOYSA-N p-methylbenzamide Natural products CC1=CC=C(C(N)=O)C=C1 UHBGYFCCKRAEHA-UHFFFAOYSA-N 0.000 claims description 3
- 201000001320 Atherosclerosis Diseases 0.000 claims description 2
- 206010020751 Hypersensitivity Diseases 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 230000007815 allergy Effects 0.000 claims description 2
- 230000033115 angiogenesis Effects 0.000 claims description 2
- 208000030159 metabolic disease Diseases 0.000 claims description 2
- RYECOJGRJDOGPP-UHFFFAOYSA-N Ethylurea Chemical compound CCNC(N)=O RYECOJGRJDOGPP-UHFFFAOYSA-N 0.000 claims 30
- 125000004944 pyrazin-3-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims 26
- 239000008194 pharmaceutical composition Substances 0.000 claims 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims 3
- 241000124008 Mammalia Species 0.000 claims 3
- 125000004432 carbon atom Chemical group C* 0.000 claims 3
- ROORDVPLFPIABK-UHFFFAOYSA-N diphenyl carbonate Chemical compound C=1C=CC=CC=1OC(=O)OC1=CC=CC=C1 ROORDVPLFPIABK-UHFFFAOYSA-N 0.000 claims 3
- 229920006395 saturated elastomer Polymers 0.000 claims 3
- 102000010400 1-phosphatidylinositol-3-kinase activity proteins Human genes 0.000 claims 2
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims 2
- GSNDBZWPIPOOKL-UHFFFAOYSA-N 2-methoxyethyl phenyl carbonate Chemical compound COCCOC(=O)OC1=CC=CC=C1 GSNDBZWPIPOOKL-UHFFFAOYSA-N 0.000 claims 2
- SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 claims 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims 2
- 208000012124 AIDS-related disease Diseases 0.000 claims 2
- 241000283690 Bos taurus Species 0.000 claims 2
- XGEGHDBEHXKFPX-UHFFFAOYSA-N N-methyl urea Chemical compound CNC(N)=O XGEGHDBEHXKFPX-UHFFFAOYSA-N 0.000 claims 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 2
- 102100036061 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform Human genes 0.000 claims 2
- 101710125691 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform Proteins 0.000 claims 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims 2
- 206010003246 arthritis Diseases 0.000 claims 2
- METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 claims 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 2
- 208000029742 colonic neoplasm Diseases 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 claims 2
- 208000032839 leukemia Diseases 0.000 claims 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 2
- 229910052757 nitrogen Inorganic materials 0.000 claims 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 2
- 239000001301 oxygen Chemical group 0.000 claims 2
- 230000004963 pathophysiological condition Effects 0.000 claims 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 2
- 239000010452 phosphate Substances 0.000 claims 2
- 230000004962 physiological condition Effects 0.000 claims 2
- 239000011593 sulfur Chemical group 0.000 claims 2
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 claims 1
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 claims 1
- ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 claims 1
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 claims 1
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 claims 1
- ITPMTXWFAVYVPE-UHFFFAOYSA-N (2-methoxyphenyl) n,n-diethylcarbamate Chemical compound CCN(CC)C(=O)OC1=CC=CC=C1OC ITPMTXWFAVYVPE-UHFFFAOYSA-N 0.000 claims 1
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 claims 1
- IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 claims 1
- YJLIKUSWRSEPSM-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-amino-8-[(4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CNC1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YJLIKUSWRSEPSM-WGQQHEPDSA-N 0.000 claims 1
- VIJSPAIQWVPKQZ-BLECARSGSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(C)=O VIJSPAIQWVPKQZ-BLECARSGSA-N 0.000 claims 1
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 claims 1
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 claims 1
- OOKAZRDERJMRCJ-KOUAFAAESA-N (3r)-7-[(1s,2s,4ar,6s,8s)-2,6-dimethyl-8-[(2s)-2-methylbutanoyl]oxy-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]-3-hydroxy-5-oxoheptanoic acid Chemical compound C1=C[C@H](C)[C@H](CCC(=O)C[C@@H](O)CC(O)=O)C2[C@@H](OC(=O)[C@@H](C)CC)C[C@@H](C)C[C@@H]21 OOKAZRDERJMRCJ-KOUAFAAESA-N 0.000 claims 1
- MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 claims 1
- YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-N 0.000 claims 1
- STPKWKPURVSAJF-LJEWAXOPSA-N (4r,5r)-5-[4-[[4-(1-aza-4-azoniabicyclo[2.2.2]octan-4-ylmethyl)phenyl]methoxy]phenyl]-3,3-dibutyl-7-(dimethylamino)-1,1-dioxo-4,5-dihydro-2h-1$l^{6}-benzothiepin-4-ol Chemical compound O[C@H]1C(CCCC)(CCCC)CS(=O)(=O)C2=CC=C(N(C)C)C=C2[C@H]1C(C=C1)=CC=C1OCC(C=C1)=CC=C1C[N+]1(CC2)CCN2CC1 STPKWKPURVSAJF-LJEWAXOPSA-N 0.000 claims 1
- VUEGYUOUAAVYAS-JGGQBBKZSA-N (6ar,9s,10ar)-9-(dimethylsulfamoylamino)-7-methyl-6,6a,8,9,10,10a-hexahydro-4h-indolo[4,3-fg]quinoline Chemical compound C1=CC([C@H]2C[C@@H](CN(C)[C@@H]2C2)NS(=O)(=O)N(C)C)=C3C2=CNC3=C1 VUEGYUOUAAVYAS-JGGQBBKZSA-N 0.000 claims 1
- DEVSOMFAQLZNKR-RJRFIUFISA-N (z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-n'-pyrazin-2-ylprop-2-enehydrazide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C2=NN(\C=C/C(=O)NNC=3N=CC=NC=3)C=N2)=C1 DEVSOMFAQLZNKR-RJRFIUFISA-N 0.000 claims 1
- YBBLOADPFWKNGS-UHFFFAOYSA-N 1,1-dimethylurea Chemical compound CN(C)C(N)=O YBBLOADPFWKNGS-UHFFFAOYSA-N 0.000 claims 1
- IGHUZFHESRDORI-UHFFFAOYSA-N 1-(3-benzylpyrido[2,3-b]pyrazin-6-yl)-3-ethylurea Chemical compound N=1C2=NC(NC(=O)NCC)=CC=C2N=CC=1CC1=CC=CC=C1 IGHUZFHESRDORI-UHFFFAOYSA-N 0.000 claims 1
- MHSLDASSAFCCDO-UHFFFAOYSA-N 1-(5-tert-butyl-2-methylpyrazol-3-yl)-3-(4-pyridin-4-yloxyphenyl)urea Chemical compound CN1N=C(C(C)(C)C)C=C1NC(=O)NC(C=C1)=CC=C1OC1=CC=NC=C1 MHSLDASSAFCCDO-UHFFFAOYSA-N 0.000 claims 1
- KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 claims 1
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 claims 1
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 claims 1
- IQOMQYXFPQLGGX-UHFFFAOYSA-N 1-[3-(2-cyclopropylethynyl)pyrido[2,3-b]pyrazin-6-yl]-3-ethylurea Chemical compound N=1C2=NC(NC(=O)NCC)=CC=C2N=CC=1C#CC1CC1 IQOMQYXFPQLGGX-UHFFFAOYSA-N 0.000 claims 1
- BUSZBGJKPVUTBK-UHFFFAOYSA-N 1-[3-(4-cyclohexylanilino)pyrido[2,3-b]pyrazin-6-yl]-3-ethylurea Chemical compound N=1C2=NC(NC(=O)NCC)=CC=C2N=CC=1NC(C=C1)=CC=C1C1CCCCC1 BUSZBGJKPVUTBK-UHFFFAOYSA-N 0.000 claims 1
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US73569805P | 2005-11-11 | 2005-11-11 | |
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EP05024693A EP1785423A1 (de) | 2005-11-11 | 2005-11-11 | Neue Pyridopyrazine und deren Verwendung als Modulatoren von Kinasen |
US84976106P | 2006-10-06 | 2006-10-06 | |
US60/849,761 | 2006-10-06 | ||
PCT/EP2006/068322 WO2007054556A1 (de) | 2005-11-11 | 2006-11-10 | Neue pyridopyrazine und deren verwendung als modulatoren von kinasen |
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KR20080068117A KR20080068117A (ko) | 2008-07-22 |
KR101400905B1 true KR101400905B1 (ko) | 2014-05-29 |
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EP (1) | EP1957487A1 (de) |
JP (1) | JP5527972B2 (de) |
KR (1) | KR101400905B1 (de) |
AR (1) | AR060010A1 (de) |
AU (1) | AU2006313701B2 (de) |
CA (1) | CA2628039A1 (de) |
HK (1) | HK1126474A1 (de) |
IL (1) | IL191139A0 (de) |
NO (1) | NO20082511L (de) |
WO (1) | WO2007054556A1 (de) |
Families Citing this family (22)
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US8217042B2 (en) | 2005-11-11 | 2012-07-10 | Zentaris Gmbh | Pyridopyrazines and their use as modulators of kinases |
EP1790342A1 (de) | 2005-11-11 | 2007-05-30 | Zentaris GmbH | Pyridopyrazin-Derivate und deren Verwendung als Modulatoren der Signaltransduktionswege |
EP1990342A1 (de) * | 2007-05-10 | 2008-11-12 | AEterna Zentaris GmbH | Pyridopyrazin-Derivate sowie Herstellungs- und Verwendungsverfahren dafür |
EP2170338A2 (de) * | 2007-07-06 | 2010-04-07 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Dna-pkcs zur modulierung von energieregulation und gehirnfunktion |
GB201007286D0 (en) | 2010-04-30 | 2010-06-16 | Astex Therapeutics Ltd | New compounds |
US8846723B2 (en) | 2010-07-29 | 2014-09-30 | Eastman Chemical Company | Esters of O-substituted hydroxy carboxylic acids and preparations thereof |
GB201020179D0 (en) | 2010-11-29 | 2011-01-12 | Astex Therapeutics Ltd | New compounds |
EP2508184A1 (de) | 2011-04-06 | 2012-10-10 | Æterna Zentaris GmbH | Pyridopyrazinderivate und ihre Verwendungen |
GB201118652D0 (en) | 2011-10-28 | 2011-12-07 | Astex Therapeutics Ltd | New compounds |
GB201118675D0 (en) | 2011-10-28 | 2011-12-14 | Astex Therapeutics Ltd | New compounds |
GB201118654D0 (en) | 2011-10-28 | 2011-12-07 | Astex Therapeutics Ltd | New compounds |
GB201118656D0 (en) | 2011-10-28 | 2011-12-07 | Astex Therapeutics Ltd | New compounds |
GB201209613D0 (en) | 2012-05-30 | 2012-07-11 | Astex Therapeutics Ltd | New compounds |
GB201209609D0 (en) | 2012-05-30 | 2012-07-11 | Astex Therapeutics Ltd | New compounds |
GB201307577D0 (en) | 2013-04-26 | 2013-06-12 | Astex Therapeutics Ltd | New compounds |
WO2015144808A1 (en) | 2014-03-26 | 2015-10-01 | Astex Therapeutics Ltd | Combinations of an fgfr inhibitor and an igf1r inhibitor |
SI3122358T1 (sl) | 2014-03-26 | 2021-04-30 | Astex Therapeutics Ltd. | Kombinacije FGFR- in CMET-inhibitorjev za zdravljenje raka |
JO3512B1 (ar) | 2014-03-26 | 2020-07-05 | Astex Therapeutics Ltd | مشتقات كينوكسالين مفيدة كمعدلات لإنزيم fgfr كيناز |
JOP20200201A1 (ar) | 2015-02-10 | 2017-06-16 | Astex Therapeutics Ltd | تركيبات صيدلانية تشتمل على n-(3.5- ثنائي ميثوكسي فينيل)-n'-(1-ميثيل إيثيل)-n-[3-(ميثيل-1h-بيرازول-4-يل) كينوكسالين-6-يل]إيثان-1.2-ثنائي الأمين |
US10478494B2 (en) | 2015-04-03 | 2019-11-19 | Astex Therapeutics Ltd | FGFR/PD-1 combination therapy for the treatment of cancer |
ES2904513T3 (es) | 2015-09-23 | 2022-04-05 | Janssen Pharmaceutica Nv | 1,4-Benzodiazepinas biheteroarilo sustituidas y usos de las mismas para el tratamiento del cáncer |
BR112018005637B1 (pt) | 2015-09-23 | 2023-11-28 | Janssen Pharmaceutica Nv | Compostos derivados de quinoxalina, quinolina e quinazolinona,composições farmacêuticas que os compreende, e uso dos referidos compostos |
Citations (2)
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WO2004104003A1 (de) | 2003-05-23 | 2004-12-02 | Zentaris Gmbh | Neue pyridopyrazine und deren verwendung als modulatoren von kinasen |
WO2004104002A1 (de) | 2003-05-23 | 2004-12-02 | Zentaris Gmbh | Neue pyridopyrazine und deren verwendung als kinase-inhibitoren |
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US3809695A (en) | 1967-04-19 | 1974-05-07 | Degussa | 2,6-dichloro-3-nitro-pyridine |
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CA2172750A1 (en) | 1995-03-28 | 1996-09-29 | Shinzo Seko | Process for producing aminonitropyridines |
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2006
- 2006-11-10 KR KR1020087014068A patent/KR101400905B1/ko not_active IP Right Cessation
- 2006-11-10 EP EP06819385A patent/EP1957487A1/de not_active Withdrawn
- 2006-11-10 CA CA002628039A patent/CA2628039A1/en not_active Abandoned
- 2006-11-10 WO PCT/EP2006/068322 patent/WO2007054556A1/de active Application Filing
- 2006-11-10 AU AU2006313701A patent/AU2006313701B2/en not_active Ceased
- 2006-11-10 JP JP2008539443A patent/JP5527972B2/ja not_active Expired - Fee Related
- 2006-11-13 AR ARP060104949A patent/AR060010A1/es unknown
-
2008
- 2008-04-29 IL IL191139A patent/IL191139A0/en unknown
- 2008-06-03 NO NO20082511A patent/NO20082511L/no not_active Application Discontinuation
-
2009
- 2009-05-26 HK HK09104745.1A patent/HK1126474A1/en not_active IP Right Cessation
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WO2004104003A1 (de) | 2003-05-23 | 2004-12-02 | Zentaris Gmbh | Neue pyridopyrazine und deren verwendung als modulatoren von kinasen |
WO2004104002A1 (de) | 2003-05-23 | 2004-12-02 | Zentaris Gmbh | Neue pyridopyrazine und deren verwendung als kinase-inhibitoren |
Also Published As
Publication number | Publication date |
---|---|
JP5527972B2 (ja) | 2014-06-25 |
AU2006313701A1 (en) | 2007-05-18 |
EP1957487A1 (de) | 2008-08-20 |
HK1126474A1 (en) | 2009-09-04 |
IL191139A0 (en) | 2008-12-29 |
KR20080068117A (ko) | 2008-07-22 |
CA2628039A1 (en) | 2007-05-18 |
AU2006313701B2 (en) | 2012-05-31 |
AR060010A1 (es) | 2008-05-21 |
WO2007054556A1 (de) | 2007-05-18 |
JP2009515853A (ja) | 2009-04-16 |
NO20082511L (no) | 2008-06-24 |
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