KR101400905B1 - 신규한 피리도피라진 및 키나제의 조절제로서의 이의 용도 - Google Patents
신규한 피리도피라진 및 키나제의 조절제로서의 이의 용도 Download PDFInfo
- Publication number
- 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
Links
- 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
- VIMACOBYXBMQCJ-CMDGGOBGSA-N 1-[3-[(e)-2-cyclohexylethenyl]pyrido[2,3-b]pyrazin-6-yl]-3-ethylurea Chemical compound N=1C2=NC(NC(=O)NCC)=CC=C2N=CC=1\C=C\C1CCCCC1 VIMACOBYXBMQCJ-CMDGGOBGSA-N 0.000 claims 1
- ZBOFKBGQZADNFB-UHFFFAOYSA-N 1-[3-[3-(2-cyclohexylethoxy)anilino]pyrido[2,3-b]pyrazin-6-yl]-3-ethylurea Chemical compound N=1C2=NC(NC(=O)NCC)=CC=C2N=CC=1NC(C=1)=CC=CC=1OCCC1CCCCC1 ZBOFKBGQZADNFB-UHFFFAOYSA-N 0.000 claims 1
- XEUGRVHOKBOVLR-UHFFFAOYSA-N 1-[3-[3-(diethylaminomethyl)-4-hydroxyanilino]pyrido[2,3-b]pyrazin-6-yl]-3-ethylurea Chemical compound N=1C2=NC(NC(=O)NCC)=CC=C2N=CC=1NC1=CC=C(O)C(CN(CC)CC)=C1 XEUGRVHOKBOVLR-UHFFFAOYSA-N 0.000 claims 1
- DEXNQCBWKKLLLW-UHFFFAOYSA-N 1-[3-[3-(dimethylamino)prop-1-ynyl]pyrido[2,3-b]pyrazin-6-yl]-3-ethylurea Chemical compound N1=CC(C#CCN(C)C)=NC2=NC(NC(=O)NCC)=CC=C21 DEXNQCBWKKLLLW-UHFFFAOYSA-N 0.000 claims 1
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 claims 1
- CQLATHFRGRKMCY-UHFFFAOYSA-N 1-ethyl-3-[3-(2-phenylethynyl)pyrido[2,3-b]pyrazin-6-yl]urea Chemical compound N=1C2=NC(NC(=O)NCC)=CC=C2N=CC=1C#CC1=CC=CC=C1 CQLATHFRGRKMCY-UHFFFAOYSA-N 0.000 claims 1
- NSHMETNGGPRFQD-UHFFFAOYSA-N 1-ethyl-3-[3-(2-thiophen-3-ylethynyl)pyrido[2,3-b]pyrazin-6-yl]urea Chemical compound N=1C2=NC(NC(=O)NCC)=CC=C2N=CC=1C#CC=1C=CSC=1 NSHMETNGGPRFQD-UHFFFAOYSA-N 0.000 claims 1
- JVUKHQQRFWUUDQ-UHFFFAOYSA-N 1-ethyl-3-[3-(3-morpholin-4-ylanilino)pyrido[2,3-b]pyrazin-6-yl]urea Chemical compound N=1C2=NC(NC(=O)NCC)=CC=C2N=CC=1NC(C=1)=CC=CC=1N1CCOCC1 JVUKHQQRFWUUDQ-UHFFFAOYSA-N 0.000 claims 1
- UZWQOMNOKMCDSS-UHFFFAOYSA-N 1-ethyl-3-[3-(3-trimethylsilylphenyl)pyrido[2,3-b]pyrazin-6-yl]urea Chemical compound N=1C2=NC(NC(=O)NCC)=CC=C2N=CC=1C1=CC=CC([Si](C)(C)C)=C1 UZWQOMNOKMCDSS-UHFFFAOYSA-N 0.000 claims 1
- ZMFGRMNHJUUFEL-UHFFFAOYSA-N 1-ethyl-3-[3-(4-imidazol-1-ylanilino)pyrido[2,3-b]pyrazin-6-yl]urea Chemical compound N=1C2=NC(NC(=O)NCC)=CC=C2N=CC=1NC(C=C1)=CC=C1N1C=CN=C1 ZMFGRMNHJUUFEL-UHFFFAOYSA-N 0.000 claims 1
- GGVTWWWATDQMCY-UHFFFAOYSA-N 1-ethyl-3-[3-(4-methylsulfonylanilino)pyrido[2,3-b]pyrazin-6-yl]urea Chemical compound N=1C2=NC(NC(=O)NCC)=CC=C2N=CC=1NC1=CC=C(S(C)(=O)=O)C=C1 GGVTWWWATDQMCY-UHFFFAOYSA-N 0.000 claims 1
- AHCAETAPHBILIV-UHFFFAOYSA-N 1-ethyl-3-[3-(4-pyrrolidin-1-ylanilino)pyrido[2,3-b]pyrazin-6-yl]urea Chemical compound N=1C2=NC(NC(=O)NCC)=CC=C2N=CC=1NC(C=C1)=CC=C1N1CCCC1 AHCAETAPHBILIV-UHFFFAOYSA-N 0.000 claims 1
- JEUJPDRXCDEJER-UHFFFAOYSA-N 1-ethyl-3-[3-[(6-morpholin-4-ylpyridin-3-yl)amino]pyrido[2,3-b]pyrazin-6-yl]urea Chemical compound N=1C2=NC(NC(=O)NCC)=CC=C2N=CC=1NC(C=N1)=CC=C1N1CCOCC1 JEUJPDRXCDEJER-UHFFFAOYSA-N 0.000 claims 1
- ZATLMIGIWOLVAL-VMPITWQZSA-N 1-ethyl-3-[3-[(e)-2-(4-fluorophenyl)ethenyl]pyrido[2,3-b]pyrazin-6-yl]urea Chemical compound N=1C2=NC(NC(=O)NCC)=CC=C2N=CC=1\C=C\C1=CC=C(F)C=C1 ZATLMIGIWOLVAL-VMPITWQZSA-N 0.000 claims 1
- GMQMXBSEXRVXKC-SNAWJCMRSA-N 1-ethyl-3-[3-[(e)-3-methoxyprop-1-enyl]pyrido[2,3-b]pyrazin-6-yl]urea Chemical compound N1=CC(\C=C\COC)=NC2=NC(NC(=O)NCC)=CC=C21 GMQMXBSEXRVXKC-SNAWJCMRSA-N 0.000 claims 1
- KXSBCNXVJMBCJX-UHFFFAOYSA-N 1-ethyl-3-[3-[2-(4-fluorophenyl)ethyl]pyrido[2,3-b]pyrazin-6-yl]urea Chemical compound N=1C2=NC(NC(=O)NCC)=CC=C2N=CC=1CCC1=CC=C(F)C=C1 KXSBCNXVJMBCJX-UHFFFAOYSA-N 0.000 claims 1
- AUUXDBHQWXPJHW-UHFFFAOYSA-N 1-ethyl-3-[3-[3-(1,2,4-triazol-1-ylmethyl)anilino]pyrido[2,3-b]pyrazin-6-yl]urea Chemical compound N=1C2=NC(NC(=O)NCC)=CC=C2N=CC=1NC(C=1)=CC=CC=1CN1C=NC=N1 AUUXDBHQWXPJHW-UHFFFAOYSA-N 0.000 claims 1
- LLNFFOKBWSXAGX-UHFFFAOYSA-N 1-ethyl-3-[3-[3-(2h-tetrazol-5-yl)anilino]pyrido[2,3-b]pyrazin-6-yl]urea Chemical compound N=1C2=NC(NC(=O)NCC)=CC=C2N=CC=1NC(C=1)=CC=CC=1C1=NN=NN1 LLNFFOKBWSXAGX-UHFFFAOYSA-N 0.000 claims 1
- RCYSRRGYVVRPJL-UHFFFAOYSA-N 1-ethyl-3-[3-[4-(4-methylpiperazin-1-yl)anilino]pyrido[2,3-b]pyrazin-6-yl]urea Chemical compound N=1C2=NC(NC(=O)NCC)=CC=C2N=CC=1NC(C=C1)=CC=C1N1CCN(C)CC1 RCYSRRGYVVRPJL-UHFFFAOYSA-N 0.000 claims 1
- PKOFFKLWACPLQZ-UHFFFAOYSA-N 1-ethyl-3-[3-[4-(morpholin-4-ylmethyl)anilino]pyrido[2,3-b]pyrazin-6-yl]urea Chemical compound N=1C2=NC(NC(=O)NCC)=CC=C2N=CC=1NC(C=C1)=CC=C1CN1CCOCC1 PKOFFKLWACPLQZ-UHFFFAOYSA-N 0.000 claims 1
- RQBCXUCSBMSRIN-UHFFFAOYSA-N 1-ethyl-3-[3-[4-(morpholin-4-ylmethyl)phenyl]pyrido[2,3-b]pyrazin-6-yl]urea Chemical compound N=1C2=NC(NC(=O)NCC)=CC=C2N=CC=1C(C=C1)=CC=C1CN1CCOCC1 RQBCXUCSBMSRIN-UHFFFAOYSA-N 0.000 claims 1
- GHALWVVVGDYINF-UHFFFAOYSA-N 1-ethyl-3-[3-[4-(piperidin-1-ylmethyl)anilino]pyrido[2,3-b]pyrazin-6-yl]urea Chemical compound N=1C2=NC(NC(=O)NCC)=CC=C2N=CC=1NC(C=C1)=CC=C1CN1CCCCC1 GHALWVVVGDYINF-UHFFFAOYSA-N 0.000 claims 1
- IMUCFSHQPYPPOU-UHFFFAOYSA-N 1-ethyl-3-[3-[4-[2-(2-methoxyethoxy)ethoxy]phenyl]pyrido[2,3-b]pyrazin-6-yl]urea Chemical compound N=1C2=NC(NC(=O)NCC)=CC=C2N=CC=1C1=CC=C(OCCOCCOC)C=C1 IMUCFSHQPYPPOU-UHFFFAOYSA-N 0.000 claims 1
- XUFXDODGXLVPNJ-UHFFFAOYSA-N 1-ethyl-3-phenylurea Chemical compound CCNC(=O)NC1=CC=CC=C1 XUFXDODGXLVPNJ-UHFFFAOYSA-N 0.000 claims 1
- WGFNXGPBPIJYLI-UHFFFAOYSA-N 2,6-difluoro-3-[(3-fluorophenyl)sulfonylamino]-n-(3-methoxy-1h-pyrazolo[3,4-b]pyridin-5-yl)benzamide Chemical compound C1=C2C(OC)=NNC2=NC=C1NC(=O)C(C=1F)=C(F)C=CC=1NS(=O)(=O)C1=CC=CC(F)=C1 WGFNXGPBPIJYLI-UHFFFAOYSA-N 0.000 claims 1
- VCUXVXLUOHDHKK-UHFFFAOYSA-N 2-(2-aminopyrimidin-4-yl)-4-(2-chloro-4-methoxyphenyl)-1,3-thiazole-5-carboxamide Chemical compound ClC1=CC(OC)=CC=C1C1=C(C(N)=O)SC(C=2N=C(N)N=CC=2)=N1 VCUXVXLUOHDHKK-UHFFFAOYSA-N 0.000 claims 1
- FMKGJQHNYMWDFJ-CVEARBPZSA-N 2-[[4-(2,2-difluoropropoxy)pyrimidin-5-yl]methylamino]-4-[[(1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl]amino]pyrimidine-5-carbonitrile Chemical compound FC(COC1=NC=NC=C1CNC1=NC=C(C(=N1)N[C@H]1CC([C@H](CC1)O)(C)C)C#N)(C)F FMKGJQHNYMWDFJ-CVEARBPZSA-N 0.000 claims 1
- VVCMGAUPZIKYTH-VGHSCWAPSA-N 2-acetyloxybenzoic acid;[(2s,3r)-4-(dimethylamino)-3-methyl-1,2-diphenylbutan-2-yl] propanoate;1,3,7-trimethylpurine-2,6-dione Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C.C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 VVCMGAUPZIKYTH-VGHSCWAPSA-N 0.000 claims 1
- YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 claims 1
- TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 claims 1
- NPRYCHLHHVWLQZ-TURQNECASA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynylpurin-8-one Chemical compound NC1=NC=C2N(C(N(C2=N1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C NPRYCHLHHVWLQZ-TURQNECASA-N 0.000 claims 1
- 125000000872 2-diethylaminoethoxy group Chemical group [H]C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])O* 0.000 claims 1
- MTFSSQVLWRFNAZ-UHFFFAOYSA-N 2-methylpropyl phenyl carbonate Chemical compound CC(C)COC(=O)OC1=CC=CC=C1 MTFSSQVLWRFNAZ-UHFFFAOYSA-N 0.000 claims 1
- MUAUTBNKPSNTFM-UHFFFAOYSA-N 2-phenylethyl carbamate Chemical compound NC(=O)OCCC1=CC=CC=C1 MUAUTBNKPSNTFM-UHFFFAOYSA-N 0.000 claims 1
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 claims 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 1
- WYFCZWSWFGJODV-MIANJLSGSA-N 4-[[(1s)-2-[(e)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-(4-methyl-2-oxopiperazin-1-yl)-3,4-dihydro-1h-isoquinoline-1-carbonyl]amino]benzoic acid Chemical compound O=C1CN(C)CCN1C1=CC=CC2=C1CCN(C(=O)\C=C\C=1C(=CC=C(Cl)C=1F)N1N=NN=C1)[C@@H]2C(=O)NC1=CC=C(C(O)=O)C=C1 WYFCZWSWFGJODV-MIANJLSGSA-N 0.000 claims 1
- NLXXFNVIMSUEFX-UHFFFAOYSA-N 4-methylbenzamide Chemical compound [CH2]C1=CC=C(C(N)=O)C=C1 NLXXFNVIMSUEFX-UHFFFAOYSA-N 0.000 claims 1
- XFJBGINZIMNZBW-CRAIPNDOSA-N 5-chloro-2-[4-[(1r,2s)-2-[2-(5-methylsulfonylpyridin-2-yl)oxyethyl]cyclopropyl]piperidin-1-yl]pyrimidine Chemical compound N1=CC(S(=O)(=O)C)=CC=C1OCC[C@H]1[C@@H](C2CCN(CC2)C=2N=CC(Cl)=CN=2)C1 XFJBGINZIMNZBW-CRAIPNDOSA-N 0.000 claims 1
- RSIWALKZYXPAGW-NSHDSACASA-N 6-(3-fluorophenyl)-3-methyl-7-[(1s)-1-(7h-purin-6-ylamino)ethyl]-[1,3]thiazolo[3,2-a]pyrimidin-5-one Chemical compound C=1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)N=C2SC=C(C)N2C(=O)C=1C1=CC=CC(F)=C1 RSIWALKZYXPAGW-NSHDSACASA-N 0.000 claims 1
- 208000030507 AIDS Diseases 0.000 claims 1
- 206010000830 Acute leukaemia Diseases 0.000 claims 1
- 208000024827 Alzheimer disease Diseases 0.000 claims 1
- 208000003174 Brain Neoplasms Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- BAYXXARRPZHOPM-UHFFFAOYSA-N C(C)N1C2=C(N=C(C1)NC1=CC=C(C=C1)S(=O)(=O)N1CCOCC1)N=C(C=C2)NC(=O)N Chemical compound C(C)N1C2=C(N=C(C1)NC1=CC=C(C=C1)S(=O)(=O)N1CCOCC1)N=C(C=C2)NC(=O)N BAYXXARRPZHOPM-UHFFFAOYSA-N 0.000 claims 1
- JQUCWIWWWKZNCS-LESHARBVSA-N C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F Chemical compound C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F JQUCWIWWWKZNCS-LESHARBVSA-N 0.000 claims 1
- ZOWAATZAMIETLY-UHFFFAOYSA-N CC(C(=O)OCO[PH2]=O)(C)C Chemical compound CC(C(=O)OCO[PH2]=O)(C)C ZOWAATZAMIETLY-UHFFFAOYSA-N 0.000 claims 1
- XANBNJQVTXEZCD-UHFFFAOYSA-N CC1=CC=C(C=C1)S(=O)(=O)O.C(OC1=CC=CC=C1)(O)=O Chemical compound CC1=CC=C(C=C1)S(=O)(=O)O.C(OC1=CC=CC=C1)(O)=O XANBNJQVTXEZCD-UHFFFAOYSA-N 0.000 claims 1
- PKMUHQIDVVOXHQ-HXUWFJFHSA-N C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O Chemical compound C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O PKMUHQIDVVOXHQ-HXUWFJFHSA-N 0.000 claims 1
- 241000283707 Capra Species 0.000 claims 1
- 206010007572 Cardiac hypertrophy Diseases 0.000 claims 1
- 208000006029 Cardiomegaly Diseases 0.000 claims 1
- 208000024172 Cardiovascular disease Diseases 0.000 claims 1
- 241000700199 Cavia porcellus Species 0.000 claims 1
- 206010008342 Cervix carcinoma Diseases 0.000 claims 1
- HEOPVJDGBFONSB-UHFFFAOYSA-N Cl.C(OC1=CC=CC=C1)(OCCOC)=O Chemical compound Cl.C(OC1=CC=CC=C1)(OCCOC)=O HEOPVJDGBFONSB-UHFFFAOYSA-N 0.000 claims 1
- 229940126657 Compound 17 Drugs 0.000 claims 1
- 229940126639 Compound 33 Drugs 0.000 claims 1
- 241000699800 Cricetinae Species 0.000 claims 1
- 206010012289 Dementia Diseases 0.000 claims 1
- 206010014733 Endometrial cancer Diseases 0.000 claims 1
- 206010014759 Endometrial neoplasm Diseases 0.000 claims 1
- 241000283074 Equus asinus Species 0.000 claims 1
- 241001331845 Equus asinus x caballus Species 0.000 claims 1
- 241000283073 Equus caballus Species 0.000 claims 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims 1
- 241000282326 Felis catus Species 0.000 claims 1
- 206010061968 Gastric neoplasm Diseases 0.000 claims 1
- 208000032612 Glial tumor Diseases 0.000 claims 1
- 206010018338 Glioma Diseases 0.000 claims 1
- 208000031886 HIV Infections Diseases 0.000 claims 1
- 208000037357 HIV infectious disease Diseases 0.000 claims 1
- 206010019695 Hepatic neoplasm Diseases 0.000 claims 1
- 206010020772 Hypertension Diseases 0.000 claims 1
- 206010061218 Inflammation Diseases 0.000 claims 1
- 208000005016 Intestinal Neoplasms Diseases 0.000 claims 1
- 206010025323 Lymphomas Diseases 0.000 claims 1
- 241000699670 Mus sp. Species 0.000 claims 1
- 208000008589 Obesity Diseases 0.000 claims 1
- 241000283973 Oryctolagus cuniculus Species 0.000 claims 1
- 206010033307 Overweight Diseases 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- 241001494479 Pecora Species 0.000 claims 1
- 241000009328 Perro Species 0.000 claims 1
- 241000700159 Rattus Species 0.000 claims 1
- 208000025747 Rheumatic disease Diseases 0.000 claims 1
- 206010039491 Sarcoma Diseases 0.000 claims 1
- 241000282898 Sus scrofa Species 0.000 claims 1
- 208000024770 Thyroid neoplasm Diseases 0.000 claims 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims 1
- 208000002495 Uterine Neoplasms Diseases 0.000 claims 1
- LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 claims 1
- SPXSEZMVRJLHQG-XMMPIXPASA-N [(2R)-1-[[4-[(3-phenylmethoxyphenoxy)methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound C(C1=CC=CC=C1)OC=1C=C(OCC2=CC=C(CN3[C@H](CCC3)CO)C=C2)C=CC=1 SPXSEZMVRJLHQG-XMMPIXPASA-N 0.000 claims 1
- PSLUFJFHTBIXMW-WYEYVKMPSA-N [(3r,4ar,5s,6s,6as,10s,10ar,10bs)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-pyridin-2-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2h-benzo[f]chromen-5-yl] acetate Chemical compound O([C@@H]1[C@@H]([C@]2(O[C@](C)(CC(=O)[C@]2(O)[C@@]2(C)[C@@H](O)CCC(C)(C)[C@@H]21)C=C)C)OC(=O)C)C(=O)NCCC1=CC=CC=N1 PSLUFJFHTBIXMW-WYEYVKMPSA-N 0.000 claims 1
- 125000002015 acyclic group Chemical group 0.000 claims 1
- 230000000172 allergic effect Effects 0.000 claims 1
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 claims 1
- 208000010668 atopic eczema Diseases 0.000 claims 1
- 235000015278 beef Nutrition 0.000 claims 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 claims 1
- 230000037396 body weight Effects 0.000 claims 1
- 210000004556 brain Anatomy 0.000 claims 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 201000010881 cervical cancer Diseases 0.000 claims 1
- 230000001684 chronic effect Effects 0.000 claims 1
- 229940125904 compound 1 Drugs 0.000 claims 1
- 229940125773 compound 10 Drugs 0.000 claims 1
- 229940125797 compound 12 Drugs 0.000 claims 1
- 229940126543 compound 14 Drugs 0.000 claims 1
- 229940125758 compound 15 Drugs 0.000 claims 1
- 229940126142 compound 16 Drugs 0.000 claims 1
- 229940125782 compound 2 Drugs 0.000 claims 1
- 229940125810 compound 20 Drugs 0.000 claims 1
- 229940126086 compound 21 Drugs 0.000 claims 1
- 229940126208 compound 22 Drugs 0.000 claims 1
- 229940125833 compound 23 Drugs 0.000 claims 1
- 229940125961 compound 24 Drugs 0.000 claims 1
- 229940125846 compound 25 Drugs 0.000 claims 1
- 229940125851 compound 27 Drugs 0.000 claims 1
- 229940127204 compound 29 Drugs 0.000 claims 1
- 229940126214 compound 3 Drugs 0.000 claims 1
- 229940125877 compound 31 Drugs 0.000 claims 1
- 229940125807 compound 37 Drugs 0.000 claims 1
- 229940125844 compound 46 Drugs 0.000 claims 1
- 229940127271 compound 49 Drugs 0.000 claims 1
- 229940125898 compound 5 Drugs 0.000 claims 1
- 229940126545 compound 53 Drugs 0.000 claims 1
- 229940127113 compound 57 Drugs 0.000 claims 1
- 229940126179 compound 72 Drugs 0.000 claims 1
- 206010012601 diabetes mellitus Diseases 0.000 claims 1
- BJXYHBKEQFQVES-NWDGAFQWSA-N enpatoran Chemical compound N[C@H]1CN(C[C@H](C1)C(F)(F)F)C1=C2C=CC=NC2=C(C=C1)C#N BJXYHBKEQFQVES-NWDGAFQWSA-N 0.000 claims 1
- GWNFQAKCJYEJEW-UHFFFAOYSA-N ethyl 3-[8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanoylamino]benzoate Chemical compound CCOC(=O)C1=CC(NC(=O)CCCCCCCSC2=NN=C(CC3=NN(C)C(=O)C4=CC=CC=C34)N2C)=CC=C1 GWNFQAKCJYEJEW-UHFFFAOYSA-N 0.000 claims 1
- XLHQVFXFSMTJDC-UHFFFAOYSA-N ethyl 5-[[6-(ethylcarbamoylamino)pyrido[2,3-b]pyrazin-3-yl]amino]-2-hydroxybenzoate Chemical compound N=1C2=NC(NC(=O)NCC)=CC=C2N=CC=1NC1=CC=C(O)C(C(=O)OCC)=C1 XLHQVFXFSMTJDC-UHFFFAOYSA-N 0.000 claims 1
- 208000028149 female reproductive system neoplasm Diseases 0.000 claims 1
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 claims 1
- 208000019622 heart disease Diseases 0.000 claims 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims 1
- 150000004677 hydrates Chemical class 0.000 claims 1
- 230000003463 hyperproliferative effect Effects 0.000 claims 1
- 230000004054 inflammatory process Effects 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 201000009019 intestinal benign neoplasm Diseases 0.000 claims 1
- 208000028867 ischemia Diseases 0.000 claims 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 claims 1
- 210000003734 kidney Anatomy 0.000 claims 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 claims 1
- 208000014018 liver neoplasm Diseases 0.000 claims 1
- 244000144972 livestock Species 0.000 claims 1
- 208000037841 lung tumor Diseases 0.000 claims 1
- 230000001404 mediated effect Effects 0.000 claims 1
- 210000002418 meninge Anatomy 0.000 claims 1
- ZBELDPMWYXDLNY-UHFFFAOYSA-N methyl 9-(4-bromo-2-fluoroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate Chemical compound C12=C3SC(C(=N)OC)=NC3=CC=C2N=CN=C1NC1=CC=C(Br)C=C1F ZBELDPMWYXDLNY-UHFFFAOYSA-N 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- YGBMCLDVRUGXOV-UHFFFAOYSA-N n-[6-[6-chloro-5-[(4-fluorophenyl)sulfonylamino]pyridin-3-yl]-1,3-benzothiazol-2-yl]acetamide Chemical compound C1=C2SC(NC(=O)C)=NC2=CC=C1C(C=1)=CN=C(Cl)C=1NS(=O)(=O)C1=CC=C(F)C=C1 YGBMCLDVRUGXOV-UHFFFAOYSA-N 0.000 claims 1
- IOMMMLWIABWRKL-WUTDNEBXSA-N nazartinib Chemical compound C1N(C(=O)/C=C/CN(C)C)CCCC[C@H]1N1C2=C(Cl)C=CC=C2N=C1NC(=O)C1=CC=NC(C)=C1 IOMMMLWIABWRKL-WUTDNEBXSA-N 0.000 claims 1
- 210000000653 nervous system Anatomy 0.000 claims 1
- 235000020824 obesity Nutrition 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- NBFNGRDFKUJVIN-VAWYXSNFSA-N phenyl (e)-3-phenylprop-2-enoate Chemical compound C=1C=CC=CC=1/C=C/C(=O)OC1=CC=CC=C1 NBFNGRDFKUJVIN-VAWYXSNFSA-N 0.000 claims 1
- XOIJDIYJCTXRQR-UHFFFAOYSA-N phenyl n,n-diethylcarbamate Chemical compound CCN(CC)C(=O)OC1=CC=CC=C1 XOIJDIYJCTXRQR-UHFFFAOYSA-N 0.000 claims 1
- MYOHNZJKOAODMX-UHFFFAOYSA-N phenyl n,n-dimethylcarbamate Chemical compound CN(C)C(=O)OC1=CC=CC=C1 MYOHNZJKOAODMX-UHFFFAOYSA-N 0.000 claims 1
- NWJYJMNNSLMESK-UHFFFAOYSA-N phenyl nonadecanoate Chemical compound CCCCCCCCCCCCCCCCCCC(=O)OC1=CC=CC=C1 NWJYJMNNSLMESK-UHFFFAOYSA-N 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 208000023958 prostate neoplasm Diseases 0.000 claims 1
- FDBYIYFVSAHJLY-UHFFFAOYSA-N resmetirom Chemical compound N1C(=O)C(C(C)C)=CC(OC=2C(=CC(=CC=2Cl)N2C(NC(=O)C(C#N)=N2)=O)Cl)=N1 FDBYIYFVSAHJLY-UHFFFAOYSA-N 0.000 claims 1
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 229930195734 saturated hydrocarbon Natural products 0.000 claims 1
- 239000012453 solvate Substances 0.000 claims 1
- 210000002536 stromal cell Anatomy 0.000 claims 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 claims 1
- 206010046766 uterine cancer Diseases 0.000 claims 1
- 230000004663 cell proliferation Effects 0.000 abstract description 7
- 230000001575 pathological effect Effects 0.000 abstract description 5
- 239000003814 drug Substances 0.000 abstract description 4
- 238000002360 preparation method Methods 0.000 abstract description 2
- 229920000728 polyester Polymers 0.000 description 152
- 229910052698 phosphorus Inorganic materials 0.000 description 151
- 206010057190 Respiratory tract infections Diseases 0.000 description 32
- 102000038030 PI3Ks Human genes 0.000 description 13
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 12
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 12
- 102000001253 Protein Kinase Human genes 0.000 description 10
- 239000003112 inhibitor Substances 0.000 description 10
- 108060006633 protein kinase Proteins 0.000 description 10
- 230000019491 signal transduction Effects 0.000 description 10
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 9
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 9
- 230000004913 activation Effects 0.000 description 8
- 150000002632 lipids Chemical class 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 7
- 230000007730 Akt signaling Effects 0.000 description 6
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 6
- 108091008611 Protein Kinase B Proteins 0.000 description 5
- 150000005840 aryl radicals Chemical class 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 230000018109 developmental process Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 229910052736 halogen Inorganic materials 0.000 description 5
- 150000002367 halogens Chemical class 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 239000012828 PI3K inhibitor Substances 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 230000000259 anti-tumor effect Effects 0.000 description 4
- 230000010261 cell growth Effects 0.000 description 4
- 230000005754 cellular signaling Effects 0.000 description 4
- 230000001086 cytosolic effect Effects 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 4
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 description 3
- 101000950669 Homo sapiens Mitogen-activated protein kinase 9 Proteins 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- 230000037364 MAPK/ERK pathway Effects 0.000 description 3
- 102100037809 Mitogen-activated protein kinase 9 Human genes 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 230000003211 malignant effect Effects 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000026731 phosphorylation Effects 0.000 description 3
- 238000006366 phosphorylation reaction Methods 0.000 description 3
- 230000002062 proliferating effect Effects 0.000 description 3
- 102000016914 ras Proteins Human genes 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 229960003787 sorafenib Drugs 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical group NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
- KKVYYGGCHJGEFJ-UHFFFAOYSA-N 1-n-(4-chlorophenyl)-6-methyl-5-n-[3-(7h-purin-6-yl)pyridin-2-yl]isoquinoline-1,5-diamine Chemical compound N=1C=CC2=C(NC=3C(=CC=CN=3)C=3C=4N=CNC=4N=CN=3)C(C)=CC=C2C=1NC1=CC=C(Cl)C=C1 KKVYYGGCHJGEFJ-UHFFFAOYSA-N 0.000 description 2
- BHHMPZQRVWVAAR-UHFFFAOYSA-N 7-bromo-8-methylpyrido[2,3-b]pyrazine Chemical compound C1=CN=C2C(C)=C(Br)C=NC2=N1 BHHMPZQRVWVAAR-UHFFFAOYSA-N 0.000 description 2
- 108010005721 B 581 Proteins 0.000 description 2
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 2
- 108091006027 G proteins Proteins 0.000 description 2
- 102000030782 GTP binding Human genes 0.000 description 2
- 108091000058 GTP-Binding Proteins 0.000 description 2
- 101150100676 Map2k1 gene Proteins 0.000 description 2
- 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 description 2
- 101100381978 Mus musculus Braf gene Proteins 0.000 description 2
- XEDJGCIOZDHXOR-JTQLQIEISA-N N-(2-chloro-4-methylpyridin-3-yl)-6-[4-ethyl-3-(hydroxymethyl)-5-oxo-1,2,4-triazol-1-yl]-5-fluoro-2-[(2S)-1,1,1-trifluoropropan-2-yl]oxypyridine-3-carboxamide Chemical compound ClC1=NC=CC(=C1NC(C1=C(N=C(C(=C1)F)N1N=C(N(C1=O)CC)CO)O[C@H](C(F)(F)F)C)=O)C XEDJGCIOZDHXOR-JTQLQIEISA-N 0.000 description 2
- 102000043276 Oncogene Human genes 0.000 description 2
- 108700020796 Oncogene Proteins 0.000 description 2
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 2
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 2
- 102000052575 Proto-Oncogene Human genes 0.000 description 2
- 108700020978 Proto-Oncogene Proteins 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- 230000001594 aberrant effect Effects 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 125000005018 aryl alkenyl group Chemical group 0.000 description 2
- 230000031018 biological processes and functions Effects 0.000 description 2
- IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 230000012292 cell migration Effects 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 229940043355 kinase inhibitor Drugs 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 2
- 230000009822 protein phosphorylation Effects 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- RSNQVABHABAKEZ-UHFFFAOYSA-N 2,3-diphenylquinoxaline Chemical class C1=CC=CC=C1C1=NC2=CC=CC=C2N=C1C1=CC=CC=C1 RSNQVABHABAKEZ-UHFFFAOYSA-N 0.000 description 1
- WVAKRQOMAINQPU-UHFFFAOYSA-N 2-[4-[2-[5-(2,2-dimethylbutyl)-1h-imidazol-2-yl]ethyl]phenyl]pyridine Chemical compound N1C(CC(C)(C)CC)=CN=C1CCC1=CC=C(C=2N=CC=CC=2)C=C1 WVAKRQOMAINQPU-UHFFFAOYSA-N 0.000 description 1
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 1
- 101100348565 Arabidopsis thaliana NHD1 gene Proteins 0.000 description 1
- 102000002804 Ataxia Telangiectasia Mutated Proteins Human genes 0.000 description 1
- 108010004586 Ataxia Telangiectasia Mutated Proteins Proteins 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- 101150033765 BAG1 gene Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 108091007958 Class I PI3Ks Proteins 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102100031480 Dual specificity mitogen-activated protein kinase kinase 1 Human genes 0.000 description 1
- 239000012824 ERK inhibitor Substances 0.000 description 1
- 108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 1
- 102000007665 Extracellular Signal-Regulated MAP Kinases Human genes 0.000 description 1
- 101710165567 Extracellular signal-regulated kinase 1 Proteins 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 102000002254 Glycogen Synthase Kinase 3 Human genes 0.000 description 1
- 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 description 1
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 1
- 101001014196 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 1 Proteins 0.000 description 1
- 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 1
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 1
- 108010044467 Isoenzymes Proteins 0.000 description 1
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
- 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 description 1
- 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 description 1
- 108700015928 Mitogen-activated protein kinase 13 Proteins 0.000 description 1
- 101100335081 Mus musculus Flt3 gene Proteins 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- 101150039148 NHX1 gene Proteins 0.000 description 1
- 101100188953 Onchocerca volvulus OV16 gene Proteins 0.000 description 1
- 101000615913 Oryza sativa subsp. japonica Mitogen-activated protein kinase kinase 1 Proteins 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 102000014160 PTEN Phosphohydrolase Human genes 0.000 description 1
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 1
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 102000005765 Proto-Oncogene Proteins c-akt Human genes 0.000 description 1
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 1
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 1
- 108010029869 Proto-Oncogene Proteins c-raf Proteins 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 206010037211 Psychomotor hyperactivity Diseases 0.000 description 1
- 102100033479 RAF proto-oncogene serine/threonine-protein kinase Human genes 0.000 description 1
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 1
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 108091006662 SLC9B1 Proteins 0.000 description 1
- 102100023085 Serine/threonine-protein kinase mTOR Human genes 0.000 description 1
- 102100022894 Sodium/hydrogen exchanger 9B1 Human genes 0.000 description 1
- 101150110875 Syk gene Proteins 0.000 description 1
- 206010042971 T-cell lymphoma Diseases 0.000 description 1
- 108010045306 T134 peptide Proteins 0.000 description 1
- 108010025037 T140 peptide Proteins 0.000 description 1
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 1
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
- 239000004473 Threonine Substances 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 102100025387 Tyrosine-protein kinase JAK3 Human genes 0.000 description 1
- 101710112792 Tyrosine-protein kinase JAK3 Proteins 0.000 description 1
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- 125000005213 alkyl heteroaryl group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 150000001409 amidines Chemical group 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000035578 autophosphorylation Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000001364 causal effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000007726 cellular glucose metabolism Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- CSPJONKOEMIPFY-UHFFFAOYSA-N disulfo sulfate Chemical group OS(=O)(=O)OS(=O)(=O)OS(O)(=O)=O CSPJONKOEMIPFY-UHFFFAOYSA-N 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- ZRALSGWEFCBTJO-UHFFFAOYSA-N guanidine group Chemical group NC(=N)N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 229940121372 histone deacetylase inhibitor Drugs 0.000 description 1
- 239000003276 histone deacetylase inhibitor Substances 0.000 description 1
- 150000002466 imines Chemical group 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 description 1
- 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 description 1
- 230000006654 negative regulation of apoptotic process Effects 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 description 1
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 238000009520 phase I clinical trial Methods 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000010644 positive regulation of cell differentiation Effects 0.000 description 1
- 230000034918 positive regulation of cell growth Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 102000009929 raf Kinases Human genes 0.000 description 1
- 108010077182 raf Kinases Proteins 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000016146 regulation of heart contraction Effects 0.000 description 1
- 208000037803 restenosis Diseases 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
- 230000005748 tumor development Effects 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/16—Central respiratory analeptics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pulmonology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Neurology (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Virology (AREA)
- Urology & Nephrology (AREA)
- Dermatology (AREA)
- Obesity (AREA)
- Oncology (AREA)
- Physical Education & Sports Medicine (AREA)
- Endocrinology (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Molecular Biology (AREA)
- Pain & Pain Management (AREA)
- Communicable Diseases (AREA)
- Psychiatry (AREA)
- Ophthalmology & Optometry (AREA)
- Emergency Medicine (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US73569805P | 2005-11-11 | 2005-11-11 | |
| EP05024693A EP1785423A1 (de) | 2005-11-11 | 2005-11-11 | Neue Pyridopyrazine und deren Verwendung als Modulatoren von Kinasen |
| US60/735,698 | 2005-11-11 | ||
| EP05024693.3 | 2005-11-11 | ||
| 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 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20080068117A KR20080068117A (ko) | 2008-07-22 |
| KR101400905B1 true KR101400905B1 (ko) | 2014-05-29 |
Family
ID=37654792
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020087014068A KR101400905B1 (ko) | 2005-11-11 | 2006-11-10 | 신규한 피리도피라진 및 키나제의 조절제로서의 이의 용도 |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP1957487A1 (ja) |
| JP (1) | JP5527972B2 (ja) |
| KR (1) | KR101400905B1 (ja) |
| AR (1) | AR060010A1 (ja) |
| AU (1) | AU2006313701B2 (ja) |
| CA (1) | CA2628039A1 (ja) |
| HK (1) | HK1126474A1 (ja) |
| IL (1) | IL191139A0 (ja) |
| NO (1) | NO20082511L (ja) |
| WO (1) | WO2007054556A1 (ja) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1790342A1 (de) * | 2005-11-11 | 2007-05-30 | Zentaris GmbH | Pyridopyrazin-Derivate und deren Verwendung als Modulatoren der Signaltransduktionswege |
| US8217042B2 (en) | 2005-11-11 | 2012-07-10 | Zentaris Gmbh | Pyridopyrazines and their use as modulators of kinases |
| EP1990342A1 (en) * | 2007-05-10 | 2008-11-12 | AEterna Zentaris GmbH | Pyridopyrazine Derivatives, Process of Manufacturing and Uses thereof |
| US20100130597A1 (en) * | 2007-07-06 | 2010-05-27 | The United State Of America, As Represented By The Secretary Of The Dept Of Health And Human Service | Dna-pkcs modulates energy regulation and brain function |
| 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 (en) | 2011-04-06 | 2012-10-10 | Æterna Zentaris GmbH | Pyridopyrazine derivatives and their use |
| 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 |
| GB201118652D0 (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 |
| GB201209609D0 (en) | 2012-05-30 | 2012-07-11 | Astex Therapeutics Ltd | New compounds |
| GB201209613D0 (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 |
| KR102479696B1 (ko) | 2014-03-26 | 2022-12-22 | 아스텍스 테라퓨틱스 리미티드 | Fgfr 억제제 및 igf1r 억제제의 조합물 |
| JO3512B1 (ar) | 2014-03-26 | 2020-07-05 | Astex Therapeutics Ltd | مشتقات كينوكسالين مفيدة كمعدلات لإنزيم fgfr كيناز |
| RU2715236C2 (ru) | 2014-03-26 | 2020-02-26 | Астекс Терапьютикс Лтд | Комбинации |
| 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 |
| BR112018005625B1 (pt) | 2015-09-23 | 2023-11-14 | Janssen Pharmaceutica N.V | Compostos derivados de quinolina, piridopirazina, naftiridina e quinazolinona, composições farmacêuticas que os compreende e uso dos mesmos |
| ES2811845T3 (es) | 2015-09-23 | 2021-03-15 | Janssen Pharmaceutica Nv | Heterociclos tricíclicos para el tratamiento del cáncer |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004104002A1 (de) | 2003-05-23 | 2004-12-02 | Zentaris Gmbh | Neue pyridopyrazine und deren verwendung als kinase-inhibitoren |
| WO2004104003A1 (de) | 2003-05-23 | 2004-12-02 | Zentaris Gmbh | Neue pyridopyrazine und deren verwendung als modulatoren von kinasen |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3809695A (en) | 1967-04-19 | 1974-05-07 | Degussa | 2,6-dichloro-3-nitro-pyridine |
| US5700823A (en) * | 1994-01-07 | 1997-12-23 | Sugen, Inc. | Treatment of platelet derived growth factor related disorders such as cancers |
| EP0735025B1 (en) | 1995-03-28 | 1998-07-01 | Sumitomo Chemical Company Limited | Process for producing aminonitropyridines |
| UA71555C2 (en) * | 1997-10-06 | 2004-12-15 | Zentaris Gmbh | Methods for modulating function of serine/threonine protein kinases by 5-azaquinoline derivatives |
| ATE529109T1 (de) | 1997-12-22 | 2011-11-15 | Bayer Healthcare Llc | Hemmung der p38 kinase aktivität durch substituierte heterocyclische harnstoffe |
| KR20010101203A (ko) | 1998-12-15 | 2001-11-14 | 로즈 암스트롱, 크리스틴 에이. 트러트웨인 | Ｍｅｋ 저해제의 이식 조직 거부를 예방하기 위한 용도 |
| ID30250A (id) | 1998-12-22 | 2001-11-15 | Warner Lambert Co | Kemoterapi kombinasi |
| ATE502941T1 (de) | 2000-04-25 | 2011-04-15 | Icos Corp | Hemmer der menschlichen phosphatidyl-inositol-3- kinase delta |
| OA12333A (en) | 2000-07-19 | 2004-04-06 | Warner Lambert Co | Oxygenated esters of 4-iodo phenylamino benzhydroxamic acids. |
| KR20100107509A (ko) | 2001-09-14 | 2010-10-05 | 9222-9129 퀘벡 인코포레이티드 | 히스톤 데아세틸라아제의 억제제 |
| AU2003210969A1 (en) | 2002-02-11 | 2003-09-04 | Bayer Corporation | Aryl ureas with raf kinase and angiogenesis inhibiting activity |
| CA2480800C (en) | 2002-04-08 | 2008-09-23 | Mark T. Bilodeau | Inhibitors of akt activity |
| AU2003230802B2 (en) | 2002-04-08 | 2007-08-09 | Merck Sharp & Dohme Corp. | Inhibitors of Akt activity |
| EP1496981A2 (en) | 2002-04-08 | 2005-01-19 | Merck & Co., Inc. | Method of treating cancer |
| EP1538907A4 (en) | 2002-07-02 | 2008-12-24 | Southern Res Inst | FTSZ-HEMMER AND ITS USE |
| WO2004017950A2 (en) | 2002-08-22 | 2004-03-04 | Piramed Limited | Phosphadidylinositol 3,5-biphosphate inhibitors as anti-viral agents |
| RS20050901A (en) * | 2003-06-05 | 2007-12-31 | Zentaris Gmbh., | Indole derivatives with apoptosis- inducing effect |
| WO2005007099A2 (en) * | 2003-07-10 | 2005-01-27 | Imclone Systems Incorporated | Pkb inhibitors as anti-tumor agents |
| CA2548172A1 (en) | 2003-12-04 | 2005-06-23 | Vertex Pharmaceuticals Incorporated | Quinoxalines useful as inhibitors of protein kinases |
| EP1790342A1 (de) * | 2005-11-11 | 2007-05-30 | Zentaris GmbH | Pyridopyrazin-Derivate und deren Verwendung als Modulatoren der Signaltransduktionswege |
-
2006
- 2006-11-10 CA CA002628039A patent/CA2628039A1/en not_active Abandoned
- 2006-11-10 KR KR1020087014068A patent/KR101400905B1/ko not_active IP Right Cessation
- 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 EP EP06819385A patent/EP1957487A1/de not_active Withdrawn
- 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
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004104002A1 (de) | 2003-05-23 | 2004-12-02 | Zentaris Gmbh | Neue pyridopyrazine und deren verwendung als kinase-inhibitoren |
| WO2004104003A1 (de) | 2003-05-23 | 2004-12-02 | Zentaris Gmbh | Neue pyridopyrazine und deren verwendung als modulatoren von kinasen |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1957487A1 (de) | 2008-08-20 |
| WO2007054556A1 (de) | 2007-05-18 |
| JP5527972B2 (ja) | 2014-06-25 |
| KR20080068117A (ko) | 2008-07-22 |
| IL191139A0 (en) | 2008-12-29 |
| NO20082511L (no) | 2008-06-24 |
| HK1126474A1 (en) | 2009-09-04 |
| AU2006313701B2 (en) | 2012-05-31 |
| CA2628039A1 (en) | 2007-05-18 |
| AU2006313701A1 (en) | 2007-05-18 |
| AR060010A1 (es) | 2008-05-21 |
| JP2009515853A (ja) | 2009-04-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101400905B1 (ko) | 신규한 피리도피라진 및 키나제의 조절제로서의 이의 용도 | |
| US8217042B2 (en) | Pyridopyrazines and their use as modulators of kinases | |
| US11655246B2 (en) | Aminothiazole compounds as inhibitors of CTPS1 | |
| JP7157791B2 (ja) | ジペプチジルペプチダーゼ１阻害剤としての（２ｓ）－ｎ－［（１ｓ）－１－シアノ－２－フェニルエチル］－１，４－オキサゼパン－２－カルボキサミド | |
| JP6145179B2 (ja) | ヤヌス関連キナーゼ（ＪＡＫ）の阻害剤としてのピロロ［２，３−ｄ］ピリミジン誘導体 | |
| JP6585158B2 (ja) | ヤヌスキナーゼの阻害に有用なピロロ［２，３−ｄ］ピリミジン誘導体 | |
| JP5805763B2 (ja) | Ｃ型肝炎ウイルス阻害剤 | |
| KR102050150B1 (ko) | 융합-고리 화합물, 약학 조성물 및 이들의 용도 | |
| JP4934223B2 (ja) | 化合物 | |
| AU2016204879A1 (en) | CDK Inhibitors | |
| CN101356173B (zh) | 新的吡啶并吡嗪和它们作为激酶调节剂的用途 | |
| WO2007058322A1 (ja) | 塩基性基を含有する化合物およびその用途 | |
| BRPI0912541B1 (pt) | Composto de benzeno sulfonamida tiazol, sua composição farmacêutica e seu uso | |
| JP2010521476A (ja) | Ｃ型肝炎の治療のための化合物 | |
| JP2013515733A (ja) | β−トリプターゼインヒビターとしてのインドリル−ピペリジニルベンジルアミン | |
| EP3492454A1 (en) | Compounds | |
| WO2021212039A1 (en) | Inhibitors of cysteine proteases and methods of use thereof | |
| RU2515944C2 (ru) | ПРОИЗВОДНЫЕ ПИРИДОПИРАЗИНА, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И СПОСОБ ЛЕЧЕНИЯ ИЛИ ПРОФИЛАКТИКИ ФИЗИОЛОГИЧЕСКИХ И/ИЛИ ПАТОФИЗИОЛОГИЧЕСКИХ СОСТОЯНИЙ ПОСРЕДСТВОМ ИНГИБИРОВАНИЯ ФЕРМЕНТОВ ERK, ERK1, ERK2, PI3K, PI3Kальфа, PI3Kбета, PI3Kгамма, PI3Kдельта, PI3K-С2альфа, PI3K-С2бета, PI3K-Vps34Р (ВАРИАНТЫ) | |
| KR20240038996A (ko) | 코로나바이러스 관련 질환의 치료를 위한 화합물 및 조성물 | |
| TWI392675B (zh) | 新穎之吡啶並吡嗪類及其作為激酶調節劑之用途 | |
| MX2008006066A (en) | Novel pyridopyrazines and their use as modulators of kinases | |
| WO2024121753A1 (en) | Polq inhibitors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A201 | Request for examination | ||
| E902 | Notification of reason for refusal | ||
| E701 | Decision to grant or registration of patent right | ||
| GRNT | Written decision to grant | ||
| LAPS | Lapse due to unpaid annual fee |