DK2834237T3 - HETEROCYCLYL COMPOUNDS AS MEK INHITORS - Google Patents

Info

Publication number

DK2834237T3

DK2834237T3 DK13712929.2T DK13712929T DK2834237T3 DK 2834237 T3 DK2834237 T3 DK 2834237T3 DK 13712929 T DK13712929 T DK 13712929T DK 2834237 T3 DK2834237 T3 DK 2834237T3

Authority

DK

Denmark

Prior art keywords

compound

amino

fluoro

substituted

alkyl

Prior art date

2012-03-14

Links

• Espacenet
• Global Dossier
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 208
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 48
• 150000003839 salts Chemical class 0.000 claims abstract description 38
• 239000003814 drug Substances 0.000 claims abstract description 15
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 14
• -1 perhaloalkyl Chemical group 0.000 claims description 192
• 125000000217 alkyl group Chemical group 0.000 claims description 151
• 125000000623 heterocyclic group Chemical group 0.000 claims description 94
• 239000001257 hydrogen Substances 0.000 claims description 71
• 229910052739 hydrogen Inorganic materials 0.000 claims description 71
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 65
• 150000002431 hydrogen Chemical group 0.000 claims description 52
• 206010028980 Neoplasm Diseases 0.000 claims description 49
• 125000003342 alkenyl group Chemical group 0.000 claims description 49
• 125000003118 aryl group Chemical group 0.000 claims description 48
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 41
• 229910052736 halogen Inorganic materials 0.000 claims description 37
• 150000002367 halogens Chemical class 0.000 claims description 37
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 36
• 229910052757 nitrogen Inorganic materials 0.000 claims description 35
• 125000001424 substituent group Chemical group 0.000 claims description 34
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 26
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 21
• 201000011510 cancer Diseases 0.000 claims description 20
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 20
• 238000011282 treatment Methods 0.000 claims description 20
• 208000035475 disorder Diseases 0.000 claims description 19
• 125000004043 oxo group Chemical group O=* 0.000 claims description 19
• 229910052799 carbon Inorganic materials 0.000 claims description 18
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 15
• 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 claims description 15
• 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 claims description 15
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 13
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
• 229910052740 iodine Inorganic materials 0.000 claims description 12
• QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 12
• 229910052705 radium Inorganic materials 0.000 claims description 12
• 229910052701 rubidium Inorganic materials 0.000 claims description 12
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 11
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
• 239000003937 drug carrier Substances 0.000 claims description 8
• 125000001188 haloalkyl group Chemical group 0.000 claims description 8
• 230000002401 inhibitory effect Effects 0.000 claims description 8
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
• 239000003085 diluting agent Substances 0.000 claims description 7
• 201000010099 disease Diseases 0.000 claims description 7
• 229940079593 drug Drugs 0.000 claims description 7
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
• 230000002265 prevention Effects 0.000 claims description 7
• 230000002062 proliferating effect Effects 0.000 claims description 7
• KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 6
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 6
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
• 208000037803 restenosis Diseases 0.000 claims description 6
• XASQAVGQTUPCTM-UHFFFAOYSA-N 1-[3-(azetidine-1-carbonyl)phenyl]-3-cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethylpyrido[4,3-d]pyrimidine-2,4,7-trione Chemical compound O=C1N(C2CC2)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1C(=O)N1CCC1 XASQAVGQTUPCTM-UHFFFAOYSA-N 0.000 claims description 5
• WULJLXCYEXYRCV-UHFFFAOYSA-N 5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-1-[3-(morpholine-4-carbonyl)phenyl]pyrido[4,3-d]pyrimidine-2,4,7-trione Chemical compound O=C1NC(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1C(=O)N1CCOCC1 WULJLXCYEXYRCV-UHFFFAOYSA-N 0.000 claims description 5
• 201000004681 Psoriasis Diseases 0.000 claims description 5
• 230000001404 mediated effect Effects 0.000 claims description 5
• 230000035755 proliferation Effects 0.000 claims description 5
• VJOPRDRLZRBOFJ-UHFFFAOYSA-N 1-[3-(azetidine-1-carbonyl)phenyl]-5-(2-fluoro-4-iodoanilino)-3,6,8-trimethylpyrido[4,3-d]pyrimidine-2,4,7-trione Chemical compound O=C1N(C)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1C(=O)N1CCC1 VJOPRDRLZRBOFJ-UHFFFAOYSA-N 0.000 claims description 4
• MHTUXLULBAURFV-UHFFFAOYSA-N 5-(2-fluoro-4-iodoanilino)-1-[3-(3-hydroxypyrrolidine-1-carbonyl)phenyl]-6,8-dimethylpyrido[4,3-d]pyrimidine-2,4,7-trione Chemical compound O=C1NC(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1C(=O)N1CCC(O)C1 MHTUXLULBAURFV-UHFFFAOYSA-N 0.000 claims description 4
• IBWFFGPLAWQKNO-UHFFFAOYSA-N 5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-1-[3-(piperazine-1-carbonyl)phenyl]pyrido[4,3-d]pyrimidine-2,4,7-trione Chemical compound O=C1NC(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1C(=O)N1CCNCC1 IBWFFGPLAWQKNO-UHFFFAOYSA-N 0.000 claims description 4
• 125000002393 azetidinyl group Chemical group 0.000 claims description 4
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 4
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
• 229910052731 fluorine Inorganic materials 0.000 claims description 4
• 230000012010 growth Effects 0.000 claims description 4
• 208000027866 inflammatory disease Diseases 0.000 claims description 4
• 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 description 4
• 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 description 3
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
• 208000023275 Autoimmune disease Diseases 0.000 claims description 3
• 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 description 3
• 102000004190 Enzymes Human genes 0.000 claims description 3
• 108090000790 Enzymes Proteins 0.000 claims description 3
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
• 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 description 3
• 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 description 3
• 229940125904 compound 1 Drugs 0.000 claims description 3
• 229940125782 compound 2 Drugs 0.000 claims description 3
• 229940125833 compound 23 Drugs 0.000 claims description 3
• 229940125961 compound 24 Drugs 0.000 claims description 3
• 229940126179 compound 72 Drugs 0.000 claims description 3
• 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 description 3
• 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 description 3
• 239000011737 fluorine Substances 0.000 claims description 3
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
• 125000002757 morpholinyl group Chemical group 0.000 claims description 3
• 125000004193 piperazinyl group Chemical group 0.000 claims description 3
• ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 claims description 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 description 2
• 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 description 2
• 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 description 2
• 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 description 2
• 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 description 2
• 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 description 2
• GCTFTMWXZFLTRR-GFCCVEGCSA-N (2r)-2-amino-n-[3-(difluoromethoxy)-4-(1,3-oxazol-5-yl)phenyl]-4-methylpentanamide Chemical compound FC(F)OC1=CC(NC(=O)[C@H](N)CC(C)C)=CC=C1C1=CN=CO1 GCTFTMWXZFLTRR-GFCCVEGCSA-N 0.000 claims description 2
• 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 description 2
• 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 description 2
• 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 description 2
• WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 claims description 2
• STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 claims description 2
• 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 description 2
• UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 claims description 2
• 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 description 2
• HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 claims description 2
• 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 description 2
• 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 description 2
• KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 claims description 2
• 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 description 2
• 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 description 2
• IXJABYRUZCCLON-UHFFFAOYSA-N 1-[3-(1,1-dioxo-1,3-thiazolidine-3-carbonyl)phenyl]-5-(2-fluoro-4-iodoanilino)-6,8-dimethylpyrido[4,3-d]pyrimidine-2,4,7-trione Chemical compound Cc1c2n(-c3cccc(c3)C(=O)N3CCS(=O)(=O)C3)c(=O)[nH]c(=O)c2c(Nc2ccc(I)cc2F)n(C)c1=O IXJABYRUZCCLON-UHFFFAOYSA-N 0.000 claims description 2
• QIAJBIYQZWEFNJ-UHFFFAOYSA-N 1-[3-[2-(azetidin-1-yl)-2-oxoethyl]phenyl]-5-(2-fluoro-4-iodoanilino)-3,6,8-trimethylpyrido[4,3-d]pyrimidine-2,4,7-trione Chemical compound O=C1N(C)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1CC(=O)N1CCC1 QIAJBIYQZWEFNJ-UHFFFAOYSA-N 0.000 claims description 2
• 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 description 2
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
• 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 description 2
• 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 description 2
• ULJYHOHIKSWUAO-UHFFFAOYSA-N 2-[3-[3-ethyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]-n,n-dimethylacetamide Chemical compound C12=C(C)C(=O)N(C)C(NC=3C(=CC(I)=CC=3)F)=C2C(=O)N(CC)C(=O)N1C1=CC=CC(CC(=O)N(C)C)=C1 ULJYHOHIKSWUAO-UHFFFAOYSA-N 0.000 claims description 2
• WIFSFWYMBDVDIY-UHFFFAOYSA-N 2-[3-[5-(2-fluoro-4-iodoanilino)-3,6,8-trimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenoxy]-n-methylacetamide Chemical compound CNC(=O)COC1=CC=CC(N2C(N(C)C(=O)C3=C(NC=4C(=CC(I)=CC=4)F)N(C)C(=O)C(C)=C32)=O)=C1 WIFSFWYMBDVDIY-UHFFFAOYSA-N 0.000 claims description 2
• IEADKAMTZQWDAR-UHFFFAOYSA-N 2-[3-[5-(2-fluoro-4-iodoanilino)-3,6,8-trimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]-2-hydroxyacetamide Chemical compound O=C1N(C)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C1=CC=CC(C(O)C(N)=O)=C1 IEADKAMTZQWDAR-UHFFFAOYSA-N 0.000 claims description 2
• ZFUHSUABBJHMLP-UHFFFAOYSA-N 2-[3-[5-(2-fluoro-4-iodoanilino)-3,6,8-trimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]-n,n-dimethylacetamide Chemical compound CN(C)C(=O)CC1=CC=CC(N2C(N(C)C(=O)C3=C(NC=4C(=CC(I)=CC=4)F)N(C)C(=O)C(C)=C32)=O)=C1 ZFUHSUABBJHMLP-UHFFFAOYSA-N 0.000 claims description 2
• GBWADMXNJIMJLW-UHFFFAOYSA-N 2-[3-[5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenoxy]-n-methylacetamide Chemical compound CNC(=O)COC1=CC=CC(N2C(NC(=O)C3=C(NC=4C(=CC(I)=CC=4)F)N(C)C(=O)C(C)=C32)=O)=C1 GBWADMXNJIMJLW-UHFFFAOYSA-N 0.000 claims description 2
• PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 claims description 2
• 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 description 2
• 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 description 2
• 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 description 2
• 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 description 2
• LFOIDLOIBZFWDO-UHFFFAOYSA-N 2-methoxy-6-[6-methoxy-4-[(3-phenylmethoxyphenyl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole Chemical compound N1=C2SC(OC)=NN2C=C1C(OC1=CC(OC)=C2)=CC1=C2OCC(C=1)=CC=CC=1OCC1=CC=CC=C1 LFOIDLOIBZFWDO-UHFFFAOYSA-N 0.000 claims description 2
• 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 description 2
• ZXXNVPPWQOWCCJ-UHFFFAOYSA-N 3-cyclopropyl-5-(2-fluoro-4-iodoanilino)-1-[3-[2-(3-hydroxyazetidin-1-yl)-2-oxoethyl]phenyl]-6,8-dimethylpyrido[4,3-d]pyrimidine-2,4,7-trione Chemical compound O=C1N(C2CC2)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1CC(=O)N1CC(O)C1 ZXXNVPPWQOWCCJ-UHFFFAOYSA-N 0.000 claims description 2
• VYFUCHDKXFZONB-UHFFFAOYSA-N 3-cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-1-[3-(pyrrolidine-1-carbonyl)phenyl]pyrido[4,3-d]pyrimidine-2,4,7-trione Chemical compound O=C1N(C2CC2)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1C(=O)N1CCCC1 VYFUCHDKXFZONB-UHFFFAOYSA-N 0.000 claims description 2
• 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 description 2
• DQAZPZIYEOGZAF-UHFFFAOYSA-N 4-ethyl-n-[4-(3-ethynylanilino)-7-methoxyquinazolin-6-yl]piperazine-1-carboxamide Chemical compound C1CN(CC)CCN1C(=O)NC(C(=CC1=NC=N2)OC)=CC1=C2NC1=CC=CC(C#C)=C1 DQAZPZIYEOGZAF-UHFFFAOYSA-N 0.000 claims description 2
• CFELFNVDHWSLTJ-UHFFFAOYSA-N 5-(2-fluoro-4-iodoanilino)-1-[3-(4-hydroxypiperidine-1-carbonyl)phenyl]-6,8-dimethylpyrido[4,3-d]pyrimidine-2,4,7-trione Chemical compound O=C1NC(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1C(=O)N1CCC(O)CC1 CFELFNVDHWSLTJ-UHFFFAOYSA-N 0.000 claims description 2
• XJLVCYFECJVVNN-UHFFFAOYSA-N 5-(2-fluoro-4-iodoanilino)-1-[3-[2-(3-hydroxyazetidin-1-yl)-2-oxoethyl]phenyl]-3,6,8-trimethylpyrido[4,3-d]pyrimidine-2,4,7-trione Chemical compound O=C1N(C)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1CC(=O)N1CC(O)C1 XJLVCYFECJVVNN-UHFFFAOYSA-N 0.000 claims description 2
• OYZSSRAPPUOOMP-UHFFFAOYSA-N 5-(2-fluoro-4-iodoanilino)-3,6,8-trimethyl-1-[3-(morpholine-4-carbonyl)phenyl]pyrido[4,3-d]pyrimidine-2,4,7-trione Chemical compound O=C1N(C)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1C(=O)N1CCOCC1 OYZSSRAPPUOOMP-UHFFFAOYSA-N 0.000 claims description 2
• RKEDKTQEQYUDSD-UHFFFAOYSA-N 5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-1-[3-(4-methylpiperazine-1-carbonyl)phenyl]pyrido[4,3-d]pyrimidine-2,4,7-trione Chemical compound C1CN(C)CCN1C(=O)C1=CC=CC(N2C(NC(=O)C3=C(NC=4C(=CC(I)=CC=4)F)N(C)C(=O)C(C)=C32)=O)=C1 RKEDKTQEQYUDSD-UHFFFAOYSA-N 0.000 claims description 2
• 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 description 2
• 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 description 2
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
• BQXUPNKLZNSUMC-YUQWMIPFSA-N CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 Chemical compound CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 BQXUPNKLZNSUMC-YUQWMIPFSA-N 0.000 claims description 2
• 229940126657 Compound 17 Drugs 0.000 claims description 2
• 229940126639 Compound 33 Drugs 0.000 claims description 2
• 229940127007 Compound 39 Drugs 0.000 claims description 2
• LVDRREOUMKACNJ-BKMJKUGQSA-N N-[(2R,3S)-2-(4-chlorophenyl)-1-(1,4-dimethyl-2-oxoquinolin-7-yl)-6-oxopiperidin-3-yl]-2-methylpropane-1-sulfonamide Chemical compound CC(C)CS(=O)(=O)N[C@H]1CCC(=O)N([C@@H]1c1ccc(Cl)cc1)c1ccc2c(C)cc(=O)n(C)c2c1 LVDRREOUMKACNJ-BKMJKUGQSA-N 0.000 claims description 2
• RHYCHKWEYQKUPF-UHFFFAOYSA-N N-[3-[5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]cyclopropanecarboxamide Chemical compound C1(CC1)C(=O)NC1=CC(=CC=C1)N1C(NC(C=2C1=C(C(N(C=2NC1=C(C=C(C=C1)I)F)C)=O)C)=O)=O RHYCHKWEYQKUPF-UHFFFAOYSA-N 0.000 claims description 2
• OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 claims description 2
• QOVYHDHLFPKQQG-NDEPHWFRSA-N N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O Chemical compound N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O QOVYHDHLFPKQQG-NDEPHWFRSA-N 0.000 claims description 2
• PNUZDKCDAWUEGK-CYZMBNFOSA-N Sitafloxacin Chemical compound C([C@H]1N)N(C=2C(=C3C(C(C(C(O)=O)=CN3[C@H]3[C@H](C3)F)=O)=CC=2F)Cl)CC11CC1 PNUZDKCDAWUEGK-CYZMBNFOSA-N 0.000 claims description 2
• 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 description 2
• 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 description 2
• LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 claims description 2
• 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 description 2
• SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 claims description 2
• 201000004983 autoimmune atherosclerosis Diseases 0.000 claims description 2
• 229940125773 compound 10 Drugs 0.000 claims description 2
• 229940125797 compound 12 Drugs 0.000 claims description 2
• 229940126543 compound 14 Drugs 0.000 claims description 2
• 229940125758 compound 15 Drugs 0.000 claims description 2
• 229940126142 compound 16 Drugs 0.000 claims description 2
• 229940125810 compound 20 Drugs 0.000 claims description 2
• 229940126086 compound 21 Drugs 0.000 claims description 2
• 229940126208 compound 22 Drugs 0.000 claims description 2
• 229940125846 compound 25 Drugs 0.000 claims description 2
• 229940125851 compound 27 Drugs 0.000 claims description 2
• 229940127204 compound 29 Drugs 0.000 claims description 2
• 229940126214 compound 3 Drugs 0.000 claims description 2
• 229940125877 compound 31 Drugs 0.000 claims description 2
• 229940125878 compound 36 Drugs 0.000 claims description 2
• 229940125807 compound 37 Drugs 0.000 claims description 2
• 229940127573 compound 38 Drugs 0.000 claims description 2
• 229940126540 compound 41 Drugs 0.000 claims description 2
• 229940125936 compound 42 Drugs 0.000 claims description 2
• 229940125844 compound 46 Drugs 0.000 claims description 2
• 229940127271 compound 49 Drugs 0.000 claims description 2
• 229940125898 compound 5 Drugs 0.000 claims description 2
• 229940126545 compound 53 Drugs 0.000 claims description 2
• 229940127113 compound 57 Drugs 0.000 claims description 2
• 229940125900 compound 59 Drugs 0.000 claims description 2
• 230000000593 degrading effect Effects 0.000 claims description 2
• 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 description 2
• 239000011630 iodine Substances 0.000 claims description 2
• 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 description 2
• 230000002147 killing effect Effects 0.000 claims description 2
• RENRQMCACQEWFC-UGKGYDQZSA-N lnp023 Chemical compound C1([C@H]2N(CC=3C=4C=CNC=4C(C)=CC=3OC)CC[C@@H](C2)OCC)=CC=C(C(O)=O)C=C1 RENRQMCACQEWFC-UGKGYDQZSA-N 0.000 claims description 2
• 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 2
• PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 claims description 2
• 208000000587 small cell lung carcinoma Diseases 0.000 claims description 2
• 229910052717 sulfur Inorganic materials 0.000 claims description 2
• 239000011593 sulfur Substances 0.000 claims description 2
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 8
• METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 claims 5
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 4
• PYNFZWRXUOCTHJ-UHFFFAOYSA-N n-[3-[3-cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]cyclopropanecarboxamide Chemical compound O=C1N(C2CC2)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1NC(=O)C1CC1 PYNFZWRXUOCTHJ-UHFFFAOYSA-N 0.000 claims 2
• 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
• 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
• 125000004847 2-fluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 1
• JKUNYOVTULTVIA-UHFFFAOYSA-N 2-methyl-2-phenoxypropanamide Chemical compound NC(=O)C(C)(C)OC1=CC=CC=C1 JKUNYOVTULTVIA-UHFFFAOYSA-N 0.000 claims 1
• BGAJNPLDJJBRHK-UHFFFAOYSA-N 3-[2-[5-(3-chloro-4-propan-2-yloxyphenyl)-1,3,4-thiadiazol-2-yl]-3-methyl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl]propanoic acid Chemical compound C1=C(Cl)C(OC(C)C)=CC=C1C1=NN=C(N2C(=C3CN(CCC(O)=O)CCC3=N2)C)S1 BGAJNPLDJJBRHK-UHFFFAOYSA-N 0.000 claims 1
• HCCNBKFJYUWLEX-UHFFFAOYSA-N 7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)-3-(pyrazin-2-ylmethylamino)pyrido[3,4-b]pyrazin-2-one Chemical compound O=C1N(CCOCCC)C2=CC(C=3C=NC(OC)=CC=3)=NC=C2N=C1NCC1=CN=CC=N1 HCCNBKFJYUWLEX-UHFFFAOYSA-N 0.000 claims 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 1
• 206010041067 Small cell lung cancer Diseases 0.000 claims 1
• 125000000304 alkynyl group Chemical group 0.000 claims 1
• HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 claims 1
• GWNLMRNIVDHPOC-UHFFFAOYSA-N n-[3-[5-(2-fluoro-4-iodoanilino)-3,6,8-trimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]cyclopropanecarboxamide Chemical compound O=C1N(C)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1NC(=O)C1CC1 GWNLMRNIVDHPOC-UHFFFAOYSA-N 0.000 claims 1
• 125000006299 oxetan-3-yl group Chemical group [H]C1([H])OC([H])([H])C1([H])* 0.000 claims 1
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims 1
• 238000000034 method Methods 0.000 abstract description 26
• 238000002360 preparation method Methods 0.000 abstract description 15
• 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 abstract description 4
• 230000008569 process Effects 0.000 abstract description 3
• 238000002560 therapeutic procedure Methods 0.000 abstract 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 150
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 146
• 239000011541 reaction mixture Substances 0.000 description 106
• 238000003786 synthesis reaction Methods 0.000 description 93
• 230000015572 biosynthetic process Effects 0.000 description 92
• 239000000203 mixture Substances 0.000 description 83
• 239000000243 solution Substances 0.000 description 77
• 238000005160 1H NMR spectroscopy Methods 0.000 description 70
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 62
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 62
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 50
• 235000019439 ethyl acetate Nutrition 0.000 description 50
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 48
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 43
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 38
• 239000002904 solvent Substances 0.000 description 37
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 36
• 208000033962 Fontaine progeroid syndrome Diseases 0.000 description 34
• 229910052938 sodium sulfate Inorganic materials 0.000 description 31
• 235000011152 sodium sulphate Nutrition 0.000 description 31
• 239000012044 organic layer Substances 0.000 description 29
• 238000007792 addition Methods 0.000 description 28
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 27
• 239000000047 product Substances 0.000 description 27
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 26
• 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 26
• 238000006243 chemical reaction Methods 0.000 description 25
• 210000004027 cell Anatomy 0.000 description 24
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 23
• 239000007787 solid Substances 0.000 description 23
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
• AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 22
• OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 21
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
• 239000000706 filtrate Substances 0.000 description 21
• 238000004440 column chromatography Methods 0.000 description 20
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
• 239000012267 brine Substances 0.000 description 18
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 18
• 230000005764 inhibitory process Effects 0.000 description 17
• 239000000543 intermediate Substances 0.000 description 17
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
• 238000009472 formulation Methods 0.000 description 15
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 14
• 239000002585 base Substances 0.000 description 14
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 14
• 239000000725 suspension Substances 0.000 description 14
• GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 12
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 12
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 12
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
• 238000000746 purification Methods 0.000 description 12
• 102000001291 MAP Kinase Kinase Kinase Human genes 0.000 description 11
• 108060006687 MAP kinase kinase kinase Proteins 0.000 description 11
• 108091000080 Phosphotransferase Proteins 0.000 description 11
• 230000000694 effects Effects 0.000 description 11
• 102000020233 phosphotransferase Human genes 0.000 description 11
• 229910000027 potassium carbonate Inorganic materials 0.000 description 11
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
• 125000004432 carbon atom Chemical group C* 0.000 description 10
• 239000012043 crude product Substances 0.000 description 10
• 239000012299 nitrogen atmosphere Substances 0.000 description 10
• 235000015320 potassium carbonate Nutrition 0.000 description 10
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
• 230000037396 body weight Effects 0.000 description 9
• 125000004122 cyclic group Chemical group 0.000 description 9
• 230000026731 phosphorylation Effects 0.000 description 9
• 238000006366 phosphorylation reaction Methods 0.000 description 9
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
• 230000004913 activation Effects 0.000 description 8
• 238000001994 activation Methods 0.000 description 8
• RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 8
• 239000003795 chemical substances by application Substances 0.000 description 8
• 235000014113 dietary fatty acids Nutrition 0.000 description 8
• 239000000194 fatty acid Substances 0.000 description 8
• 229930195729 fatty acid Natural products 0.000 description 8
• 238000001914 filtration Methods 0.000 description 8
• 238000003818 flash chromatography Methods 0.000 description 8
• 239000003112 inhibitor Substances 0.000 description 8
• 239000012074 organic phase Substances 0.000 description 8
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
• XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 7
• 125000002619 bicyclic group Chemical group 0.000 description 7
• 150000002148 esters Chemical class 0.000 description 7
• 230000037361 pathway Effects 0.000 description 7
• 239000012071 phase Substances 0.000 description 7
• 239000002244 precipitate Substances 0.000 description 7
• 206010039073 rheumatoid arthritis Diseases 0.000 description 7
• 239000011780 sodium chloride Substances 0.000 description 7
• 239000004094 surface-active agent Substances 0.000 description 7
• 230000004083 survival effect Effects 0.000 description 7
• AFPHTEQTJZKQAQ-UHFFFAOYSA-N 3-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1 AFPHTEQTJZKQAQ-UHFFFAOYSA-N 0.000 description 6
• OKJNNTMNNOALEX-UHFFFAOYSA-N 5-(2-fluoro-4-iodoanilino)-1-[3-(3-hydroxypyrrolidine-1-carbonyl)phenyl]-3-[(4-methoxyphenyl)methyl]-6,8-dimethylpyrido[4,3-d]pyrimidine-2,4,7-trione Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N(C=2C=C(C=CC=2)C(=O)N2CC(O)CC2)C1=O OKJNNTMNNOALEX-UHFFFAOYSA-N 0.000 description 6
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
• 241000124008 Mammalia Species 0.000 description 6
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 6
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
• 229910006074 SO2NH2 Inorganic materials 0.000 description 6
• 239000002253 acid Substances 0.000 description 6
• VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 6
• 239000012298 atmosphere Substances 0.000 description 6
• 239000003599 detergent Substances 0.000 description 6
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 6
• 239000003480 eluent Substances 0.000 description 6
• YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 6
• 230000004614 tumor growth Effects 0.000 description 6
• OPLDWUQQNWDGEJ-UHFFFAOYSA-N (4-hydroxypiperidin-1-yl)-(3-nitrophenyl)methanone Chemical compound C1CC(O)CCN1C(=O)C1=CC=CC([N+]([O-])=O)=C1 OPLDWUQQNWDGEJ-UHFFFAOYSA-N 0.000 description 5
• LGUDMZFFJVLRBB-UHFFFAOYSA-N 1-(2-fluoro-4-iodophenyl)-5-[3-(3-hydroxypyrrolidine-1-carbonyl)anilino]-3-[(4-methoxyphenyl)methyl]-6,8-dimethylpyrido[2,3-d]pyrimidine-2,4,7-trione Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C(C(NC=2C=C(C=CC=2)C(=O)N2CC(O)CC2)=C(C)C(=O)N2C)=C2N(C=2C(=CC(I)=CC=2)F)C1=O LGUDMZFFJVLRBB-UHFFFAOYSA-N 0.000 description 5
• WUKHOVCMWXMOOA-UHFFFAOYSA-N 2-(3-nitrophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC([N+]([O-])=O)=C1 WUKHOVCMWXMOOA-UHFFFAOYSA-N 0.000 description 5
• WOUCWDTWVGFUGA-UHFFFAOYSA-N 3-[[1-(2-fluoro-4-iodophenyl)-3-[(4-methoxyphenyl)methyl]-6,8-dimethyl-2,4,7-trioxopyrido[2,3-d]pyrimidin-5-yl]amino]benzoic acid Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C(C(NC=2C=C(C=CC=2)C(O)=O)=C(C)C(=O)N2C)=C2N(C=2C(=CC(I)=CC=2)F)C1=O WOUCWDTWVGFUGA-UHFFFAOYSA-N 0.000 description 5
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
• 241000699670 Mus sp. Species 0.000 description 5
• GPWPJQBWRUZBPD-UHFFFAOYSA-N [1-(2-fluoro-4-iodophenyl)-3-[(4-methoxyphenyl)methyl]-6,8-dimethyl-2,4,7-trioxopyrido[2,3-d]pyrimidin-5-yl] 4-methylbenzenesulfonate Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C(C(OS(=O)(=O)C=2C=CC(C)=CC=2)=C(C)C(=O)N2C)=C2N(C=2C(=CC(I)=CC=2)F)C1=O GPWPJQBWRUZBPD-UHFFFAOYSA-N 0.000 description 5
• 125000005907 alkyl ester group Chemical group 0.000 description 5
• QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
• 150000001721 carbon Chemical group 0.000 description 5
• 238000001816 cooling Methods 0.000 description 5
• 229960004132 diethyl ether Drugs 0.000 description 5
• 239000010410 layer Substances 0.000 description 5
• OULWINUNYMWCJZ-UHFFFAOYSA-N methyl 3-[[1-(2-fluoro-4-iodophenyl)-3-[(4-methoxyphenyl)methyl]-6,8-dimethyl-2,4,7-trioxopyrido[2,3-d]pyrimidin-5-yl]amino]benzoate Chemical compound COC(=O)C1=CC=CC(NC=2C=3C(=O)N(CC=4C=CC(OC)=CC=4)C(=O)N(C=4C(=CC(I)=CC=4)F)C=3N(C)C(=O)C=2C)=C1 OULWINUNYMWCJZ-UHFFFAOYSA-N 0.000 description 5
• 125000002950 monocyclic group Chemical group 0.000 description 5
• 230000035772 mutation Effects 0.000 description 5
• 239000003921 oil Substances 0.000 description 5
• 235000019198 oils Nutrition 0.000 description 5
• 238000010898 silica gel chromatography Methods 0.000 description 5
• 238000012360 testing method Methods 0.000 description 5
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
• IEADKAMTZQWDAR-LJQANCHMSA-N (2r)-2-[3-[5-(2-fluoro-4-iodoanilino)-3,6,8-trimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]-2-hydroxyacetamide Chemical compound O=C1N(C)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C1=CC=CC([C@@H](O)C(N)=O)=C1 IEADKAMTZQWDAR-LJQANCHMSA-N 0.000 description 4
• ZGHLPFNFXSETAR-UHFFFAOYSA-N (3-aminophenyl)-(azetidin-1-yl)methanone Chemical compound NC1=CC=CC(C(=O)N2CCC2)=C1 ZGHLPFNFXSETAR-UHFFFAOYSA-N 0.000 description 4
• LSHKUHMETFGZQV-UHFFFAOYSA-N 1-(3-nitrophenyl)cyclopropane-1-carbonitrile Chemical compound [O-][N+](=O)C1=CC=CC(C2(CC2)C#N)=C1 LSHKUHMETFGZQV-UHFFFAOYSA-N 0.000 description 4
• VFFFGWWWEHIXRR-UHFFFAOYSA-N 2,2-difluoro-2-(3-nitrophenyl)acetamide Chemical compound NC(=O)C(F)(F)C1=CC=CC([N+]([O-])=O)=C1 VFFFGWWWEHIXRR-UHFFFAOYSA-N 0.000 description 4
• DYPBNODNBSMPST-UHFFFAOYSA-N 2-(3-aminophenyl)-2,2-difluoroacetamide Chemical compound NC(=O)C(F)(F)C1=CC=CC(N)=C1 DYPBNODNBSMPST-UHFFFAOYSA-N 0.000 description 4
• ITVSRAHBQOTMQA-UHFFFAOYSA-N 2-(3-aminophenyl)-2-methylpropanamide Chemical compound NC(=O)C(C)(C)C1=CC=CC(N)=C1 ITVSRAHBQOTMQA-UHFFFAOYSA-N 0.000 description 4
• UWEZXIIXUNXITL-UHFFFAOYSA-N 2-(3-aminophenyl)-n,n-dimethylacetamide Chemical compound CN(C)C(=O)CC1=CC=CC(N)=C1 UWEZXIIXUNXITL-UHFFFAOYSA-N 0.000 description 4
• KUNWLVWLBVXLTQ-UHFFFAOYSA-N 2-methyl-2-(3-nitrophenyl)propanamide Chemical compound NC(=O)C(C)(C)C1=CC=CC([N+]([O-])=O)=C1 KUNWLVWLBVXLTQ-UHFFFAOYSA-N 0.000 description 4
• FYRQAESAYXPEBZ-UHFFFAOYSA-N 2-methyl-2-(3-nitrophenyl)propanenitrile Chemical compound N#CC(C)(C)C1=CC=CC([N+]([O-])=O)=C1 FYRQAESAYXPEBZ-UHFFFAOYSA-N 0.000 description 4
• RFPPFWMCZMAVHU-UHFFFAOYSA-N 3-[3-[5-(2-fluoro-4-iodoanilino)-3-[(4-methoxyphenyl)methyl]-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]propanamide Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N(C=2C=C(CCC(N)=O)C=CC=2)C1=O RFPPFWMCZMAVHU-UHFFFAOYSA-N 0.000 description 4
• AUHJJQRASHFNSU-UHFFFAOYSA-N 3-[3-[5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]propanamide Chemical compound O=C1NC(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C1=CC=CC(CCC(N)=O)=C1 AUHJJQRASHFNSU-UHFFFAOYSA-N 0.000 description 4
• NXTNASSYJUXJDV-UHFFFAOYSA-N 3-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=CC(C(Cl)=O)=C1 NXTNASSYJUXJDV-UHFFFAOYSA-N 0.000 description 4
• 206010027476 Metastases Diseases 0.000 description 4
• 229920002685 Polyoxyl 35CastorOil Polymers 0.000 description 4
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
• 229930006000 Sucrose Natural products 0.000 description 4
• 239000005864 Sulphur Substances 0.000 description 4
• 230000001594 aberrant effect Effects 0.000 description 4
• 235000011054 acetic acid Nutrition 0.000 description 4
• 238000004458 analytical method Methods 0.000 description 4
• 230000033115 angiogenesis Effects 0.000 description 4
• 238000003556 assay Methods 0.000 description 4
• 229910052794 bromium Inorganic materials 0.000 description 4
• 239000003153 chemical reaction reagent Substances 0.000 description 4
• 229910052801 chlorine Inorganic materials 0.000 description 4
• NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 4
• 230000006552 constitutive activation Effects 0.000 description 4
• 239000013078 crystal Substances 0.000 description 4
• LVDAPIQZJAPZMF-UHFFFAOYSA-N ethyl 1-[(3-nitrobenzoyl)amino]cyclopropane-1-carboxylate Chemical compound C=1C=CC([N+]([O-])=O)=CC=1C(=O)NC1(C(=O)OCC)CC1 LVDAPIQZJAPZMF-UHFFFAOYSA-N 0.000 description 4
• DOFQZLCPHBQYCC-UHFFFAOYSA-N ethyl 2,2-difluoro-2-(3-nitrophenyl)acetate Chemical compound CCOC(=O)C(F)(F)C1=CC=CC([N+]([O-])=O)=C1 DOFQZLCPHBQYCC-UHFFFAOYSA-N 0.000 description 4
• 150000004665 fatty acids Chemical class 0.000 description 4
• 239000003102 growth factor Substances 0.000 description 4
• 238000002347 injection Methods 0.000 description 4
• 239000007924 injection Substances 0.000 description 4
• 239000002502 liposome Substances 0.000 description 4
• 239000007788 liquid Substances 0.000 description 4
• 239000012139 lysis buffer Substances 0.000 description 4
• UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 4
• PKVGURXCDKEJNP-UHFFFAOYSA-N n,n-dimethyl-2-(3-nitrophenyl)acetamide Chemical compound CN(C)C(=O)CC1=CC=CC([N+]([O-])=O)=C1 PKVGURXCDKEJNP-UHFFFAOYSA-N 0.000 description 4
• NTYVNOFOENJWQW-UHFFFAOYSA-N n-cyclopropyl-2-(3-nitrophenoxy)acetamide Chemical compound [O-][N+](=O)C1=CC=CC(OCC(=O)NC2CC2)=C1 NTYVNOFOENJWQW-UHFFFAOYSA-N 0.000 description 4
• QUPKQBWAYPTDRF-UHFFFAOYSA-N n-cyclopropyl-3-[5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]benzamide Chemical compound O=C1NC(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1C(=O)NC1CC1 QUPKQBWAYPTDRF-UHFFFAOYSA-N 0.000 description 4
• QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 description 4
• 239000008389 polyethoxylated castor oil Substances 0.000 description 4
• 229920001223 polyethylene glycol Polymers 0.000 description 4
• 239000003380 propellant Substances 0.000 description 4
• 239000000741 silica gel Substances 0.000 description 4
• 229910002027 silica gel Inorganic materials 0.000 description 4
• 210000003491 skin Anatomy 0.000 description 4
• 235000017557 sodium bicarbonate Nutrition 0.000 description 4
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
• 239000000126 substance Substances 0.000 description 4
• 239000005720 sucrose Substances 0.000 description 4
• 239000003981 vehicle Substances 0.000 description 4
• QEDSVXCNTVYJQR-UHFFFAOYSA-N (1,1-dioxo-1,3-thiazolidin-3-yl)-(3-nitrophenyl)methanone Chemical compound [O-][N+](=O)c1cccc(c1)C(=O)N1CCS(=O)(=O)C1 QEDSVXCNTVYJQR-UHFFFAOYSA-N 0.000 description 3
• ZEJLPPYGHJTMPH-UHFFFAOYSA-N (3-aminophenyl)-(1,1-dioxo-1,3-thiazolidin-3-yl)methanone Chemical compound NC1=CC=CC(=C1)C(=O)N1CCS(=O)(=O)C1 ZEJLPPYGHJTMPH-UHFFFAOYSA-N 0.000 description 3
• QONZJMXIRQLKMQ-UHFFFAOYSA-N (3-aminophenyl)-(1,1-dioxo-1,4-thiazinan-4-yl)methanone Chemical compound NC1=CC=CC(C(=O)N2CCS(=O)(=O)CC2)=C1 QONZJMXIRQLKMQ-UHFFFAOYSA-N 0.000 description 3
• YHDICOKYAMILRJ-UHFFFAOYSA-N (3-aminophenyl)-(4-hydroxypiperidin-1-yl)methanone Chemical compound NC1=CC=CC(C(=O)N2CCC(O)CC2)=C1 YHDICOKYAMILRJ-UHFFFAOYSA-N 0.000 description 3
• RFFVEVKGZGRRCP-UHFFFAOYSA-N (3-aminophenyl)-morpholin-4-ylmethanone Chemical compound NC1=CC=CC(C(=O)N2CCOCC2)=C1 RFFVEVKGZGRRCP-UHFFFAOYSA-N 0.000 description 3
• BUVKYOYGAYIJAE-UHFFFAOYSA-N (3-nitrophenyl)-(1,3-thiazolidin-3-yl)methanone Chemical compound [O-][N+](=O)C1=CC=CC(C(=O)N2CSCC2)=C1 BUVKYOYGAYIJAE-UHFFFAOYSA-N 0.000 description 3
• SHYLSTIEBCHGNT-UHFFFAOYSA-N (3-nitrophenyl)-thiomorpholin-4-ylmethanone Chemical compound [O-][N+](=O)C1=CC=CC(C(=O)N2CCSCC2)=C1 SHYLSTIEBCHGNT-UHFFFAOYSA-N 0.000 description 3
• RRFLFPDRTOJXTJ-UHFFFAOYSA-N (4-methylpiperazin-1-yl)(3-nitrophenyl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=CC=CC([N+]([O-])=O)=C1 RRFLFPDRTOJXTJ-UHFFFAOYSA-N 0.000 description 3
• YQCJLPQSTQGHAH-UHFFFAOYSA-N 1-(3-aminophenyl)cyclopropane-1-carboxamide Chemical compound C=1C=CC(N)=CC=1C1(C(=O)N)CC1 YQCJLPQSTQGHAH-UHFFFAOYSA-N 0.000 description 3
• FLBVTRHOTLOQDK-UHFFFAOYSA-N 1-(3-hydroxyazetidin-1-yl)-2-(3-nitrophenyl)ethanone Chemical compound C1C(O)CN1C(=O)CC1=CC=CC([N+]([O-])=O)=C1 FLBVTRHOTLOQDK-UHFFFAOYSA-N 0.000 description 3
• MNQJTFDCMDMQJE-UHFFFAOYSA-N 1-(3-nitrophenyl)cyclopropane-1-carboxamide Chemical compound C=1C=CC([N+]([O-])=O)=CC=1C1(C(=O)N)CC1 MNQJTFDCMDMQJE-UHFFFAOYSA-N 0.000 description 3
• PDIOOULXKSSSHU-UHFFFAOYSA-N 1-(azetidin-1-yl)-2-(3-nitrophenyl)ethanone Chemical compound [O-][N+](=O)C1=CC=CC(CC(=O)N2CCC2)=C1 PDIOOULXKSSSHU-UHFFFAOYSA-N 0.000 description 3
• GTOBOBXMJXSMGZ-UHFFFAOYSA-N 1-[(3-nitrobenzoyl)amino]cyclopropane-1-carboxylic acid Chemical compound C=1C=CC([N+]([O-])=O)=CC=1C(=O)NC1(C(=O)O)CC1 GTOBOBXMJXSMGZ-UHFFFAOYSA-N 0.000 description 3
• LOIRFKMKHKIDKY-UHFFFAOYSA-N 1-[3-(1,1-dioxo-1,4-thiazinane-4-carbonyl)phenyl]-5-(2-fluoro-4-iodoanilino)-6,8-dimethylpyrido[4,3-d]pyrimidine-2,4,7-trione Chemical compound O=C1NC(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1C(=O)N1CCS(=O)(=O)CC1 LOIRFKMKHKIDKY-UHFFFAOYSA-N 0.000 description 3
• LMHQYLFVGPUKDS-UHFFFAOYSA-N 2-(3-aminophenoxy)-2-methylpropanamide Chemical compound NC(=O)C(C)(C)OC1=CC=CC(N)=C1 LMHQYLFVGPUKDS-UHFFFAOYSA-N 0.000 description 3
• LQSMIJVSDLQJNN-UHFFFAOYSA-N 2-(3-aminophenoxy)-n-cyclopropylacetamide Chemical compound NC1=CC=CC(OCC(=O)NC2CC2)=C1 LQSMIJVSDLQJNN-UHFFFAOYSA-N 0.000 description 3
• BNVMXSMAEXBOQL-UHFFFAOYSA-N 2-(3-aminophenyl)-1-(3-hydroxyazetidin-1-yl)ethanone Chemical compound NC1=CC=CC(CC(=O)N2CC(O)C2)=C1 BNVMXSMAEXBOQL-UHFFFAOYSA-N 0.000 description 3
• ZKGLQRQFULXCJG-UHFFFAOYSA-N 2-(3-aminophenyl)-1-(azetidin-1-yl)ethanone Chemical compound NC1=CC=CC(CC(=O)N2CCC2)=C1 ZKGLQRQFULXCJG-UHFFFAOYSA-N 0.000 description 3
• ZRCQMVZIQQDMGI-UHFFFAOYSA-N 2-(3-aminophenyl)-n-(oxetan-3-yl)acetamide Chemical compound NC1=CC=CC(CC(=O)NC2COC2)=C1 ZRCQMVZIQQDMGI-UHFFFAOYSA-N 0.000 description 3
• DMZDYILYWMVUFP-UHFFFAOYSA-N 2-(3-aminophenyl)-n-cyclopropylacetamide Chemical compound NC1=CC=CC(CC(=O)NC2CC2)=C1 DMZDYILYWMVUFP-UHFFFAOYSA-N 0.000 description 3
• UNJYBHQBTZBCKR-UHFFFAOYSA-N 2-(3-nitrophenyl)-2-oxoacetamide Chemical compound NC(=O)C(=O)C1=CC=CC([N+]([O-])=O)=C1 UNJYBHQBTZBCKR-UHFFFAOYSA-N 0.000 description 3
• RWNYXMKCYSGXHS-UHFFFAOYSA-N 2-[3-[5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]-2-methylpropanamide Chemical compound O=C1NC(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C1=CC=CC(C(C)(C)C(N)=O)=C1 RWNYXMKCYSGXHS-UHFFFAOYSA-N 0.000 description 3
• YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 3
• HEELTFHBKYOEQB-UHFFFAOYSA-N 2-methyl-2-(3-nitrophenoxy)propanamide Chemical compound NC(=O)C(C)(C)OC1=CC=CC([N+]([O-])=O)=C1 HEELTFHBKYOEQB-UHFFFAOYSA-N 0.000 description 3
• RPLPDFUFYZSFOI-UHFFFAOYSA-N 2-methyl-2-(3-nitrophenoxy)propanoic acid Chemical compound OC(=O)C(C)(C)OC1=CC=CC([N+]([O-])=O)=C1 RPLPDFUFYZSFOI-UHFFFAOYSA-N 0.000 description 3
• ZHCZZCBDKBRRRB-UHFFFAOYSA-N 3-[5-(2-fluoro-4-iodoanilino)-3-[(4-methoxyphenyl)methyl]-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]benzoic acid Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N(C=2C=C(C=CC=2)C(O)=O)C1=O ZHCZZCBDKBRRRB-UHFFFAOYSA-N 0.000 description 3
• TVPTZAJKVALZQO-UHFFFAOYSA-N 3-amino-n-(1-carbamoylcyclopropyl)benzamide Chemical compound C=1C=CC(N)=CC=1C(=O)NC1(C(=O)N)CC1 TVPTZAJKVALZQO-UHFFFAOYSA-N 0.000 description 3
• BZXRRVWKZJEPGN-UHFFFAOYSA-N 3-amino-n-(oxan-4-yl)benzamide Chemical compound NC1=CC=CC(C(=O)NC2CCOCC2)=C1 BZXRRVWKZJEPGN-UHFFFAOYSA-N 0.000 description 3
• UMTROOQLBSFEJS-UHFFFAOYSA-N 3-amino-n-(oxetan-3-yl)benzamide Chemical compound NC1=CC=CC(C(=O)NC2COC2)=C1 UMTROOQLBSFEJS-UHFFFAOYSA-N 0.000 description 3
• BWGNEZBUQRZELY-UHFFFAOYSA-N 3-amino-n-(oxolan-3-yl)benzamide Chemical compound NC1=CC=CC(C(=O)NC2COCC2)=C1 BWGNEZBUQRZELY-UHFFFAOYSA-N 0.000 description 3
• ZRQYFWDCHZTRPJ-UHFFFAOYSA-N 3-nitro-n-(oxan-4-yl)benzamide Chemical compound [O-][N+](=O)C1=CC=CC(C(=O)NC2CCOCC2)=C1 ZRQYFWDCHZTRPJ-UHFFFAOYSA-N 0.000 description 3
• XQWQZBZQMQHIKP-UHFFFAOYSA-N 3-nitro-n-(oxetan-3-yl)benzamide Chemical compound [O-][N+](=O)C1=CC=CC(C(=O)NC2COC2)=C1 XQWQZBZQMQHIKP-UHFFFAOYSA-N 0.000 description 3
• GUQXCBKXLYQDSP-UHFFFAOYSA-N 3-nitro-n-(oxolan-3-yl)benzamide Chemical compound [O-][N+](=O)C1=CC=CC(C(=O)NC2COCC2)=C1 GUQXCBKXLYQDSP-UHFFFAOYSA-N 0.000 description 3
• HNXHAMCRQSREFL-UHFFFAOYSA-N 5-[3-(azetidine-1-carbonyl)anilino]-3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-6,8-dimethylpyrido[2,3-d]pyrimidine-2,4,7-trione Chemical compound C=1C=C(I)C=C(F)C=1N1C(=O)N(C2CC2)C(=O)C2=C1N(C)C(=O)C(C)=C2NC(C=1)=CC=CC=1C(=O)N1CCC1 HNXHAMCRQSREFL-UHFFFAOYSA-N 0.000 description 3
• 108090000695 Cytokines Proteins 0.000 description 3
• 102000004127 Cytokines Human genes 0.000 description 3
• 108010010803 Gelatin Proteins 0.000 description 3
• 206010061218 Inflammation Diseases 0.000 description 3
• 240000007472 Leucaena leucocephala Species 0.000 description 3
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 3
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• 241001465754 Metazoa Species 0.000 description 3
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 3
• 239000002202 Polyethylene glycol Substances 0.000 description 3
• 208000006011 Stroke Diseases 0.000 description 3
• 230000002159 abnormal effect Effects 0.000 description 3
• 239000013543 active substance Substances 0.000 description 3
• 239000000443 aerosol Substances 0.000 description 3
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
• 150000001412 amines Chemical class 0.000 description 3
• 230000008901 benefit Effects 0.000 description 3
• HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 3
• 230000004663 cell proliferation Effects 0.000 description 3
• BYGPRWSJAJYKOY-UHFFFAOYSA-N ethyl 2-methyl-2-(3-nitrophenoxy)propanoate Chemical compound CCOC(=O)C(C)(C)OC1=CC=CC([N+]([O-])=O)=C1 BYGPRWSJAJYKOY-UHFFFAOYSA-N 0.000 description 3
• 230000001747 exhibiting effect Effects 0.000 description 3
• 238000000605 extraction Methods 0.000 description 3
• 239000008273 gelatin Substances 0.000 description 3
• 229920000159 gelatin Polymers 0.000 description 3
• 235000019322 gelatine Nutrition 0.000 description 3
• 235000011852 gelatine desserts Nutrition 0.000 description 3
• 125000005843 halogen group Chemical group 0.000 description 3
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
• 230000004054 inflammatory process Effects 0.000 description 3
• 238000011081 inoculation Methods 0.000 description 3
• 229940043355 kinase inhibitor Drugs 0.000 description 3
• 208000032839 leukemia Diseases 0.000 description 3
• 230000000670 limiting effect Effects 0.000 description 3
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 3
• 201000001441 melanoma Diseases 0.000 description 3
• MXFOITYGEAXTJY-UHFFFAOYSA-N methyl 3-[5-(2-fluoro-4-iodoanilino)-3-[(4-methoxyphenyl)methyl]-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]benzoate Chemical compound COC(=O)C1=CC=CC(N2C(N(CC=3C=CC(OC)=CC=3)C(=O)C3=C(NC=4C(=CC(I)=CC=4)F)N(C)C(=O)C(C)=C32)=O)=C1 MXFOITYGEAXTJY-UHFFFAOYSA-N 0.000 description 3
• ODNSILCPLROTCN-UHFFFAOYSA-N morpholin-4-yl-(3-nitrophenyl)methanone Chemical compound [O-][N+](=O)C1=CC=CC(C(=O)N2CCOCC2)=C1 ODNSILCPLROTCN-UHFFFAOYSA-N 0.000 description 3
• IGLDAAUXFMDUMJ-UHFFFAOYSA-N n-(1-carbamoylcyclopropyl)-3-nitrobenzamide Chemical compound C=1C=CC([N+]([O-])=O)=CC=1C(=O)NC1(C(=O)N)CC1 IGLDAAUXFMDUMJ-UHFFFAOYSA-N 0.000 description 3
• MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
• XJRGKGCLUSRSHD-UHFFFAOYSA-N n-[1-(hydroxymethyl)cyclopropyl]-3-nitrobenzamide Chemical compound C=1C=CC([N+]([O-])=O)=CC=1C(=O)NC1(CO)CC1 XJRGKGCLUSRSHD-UHFFFAOYSA-N 0.000 description 3
• VYDNAFSMBGPHCA-UHFFFAOYSA-N n-cyclopropyl-2-(3-nitrophenyl)acetamide Chemical compound [O-][N+](=O)C1=CC=CC(CC(=O)NC2CC2)=C1 VYDNAFSMBGPHCA-UHFFFAOYSA-N 0.000 description 3
• JUSGHSITUTXLLZ-UHFFFAOYSA-N n-cyclopropyl-2-[3-[5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenoxy]acetamide Chemical compound O=C1NC(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1OCC(=O)NC1CC1 JUSGHSITUTXLLZ-UHFFFAOYSA-N 0.000 description 3
• XVQCCCJDCXVLBZ-UHFFFAOYSA-N n-cyclopropyl-2-[3-[5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]acetamide Chemical compound O=C1NC(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1CC(=O)NC1CC1 XVQCCCJDCXVLBZ-UHFFFAOYSA-N 0.000 description 3
• MSFBIVDHLICOSY-UHFFFAOYSA-N n-methyl-3-(3-nitrophenyl)prop-2-enamide Chemical compound CNC(=O)C=CC1=CC=CC([N+]([O-])=O)=C1 MSFBIVDHLICOSY-UHFFFAOYSA-N 0.000 description 3
• RQFBXBBPLGIKAK-UHFFFAOYSA-N n-tert-butyl-2-(3-nitrophenyl)-2-oxoacetamide Chemical compound CC(C)(C)NC(=O)C(=O)C1=CC=CC([N+]([O-])=O)=C1 RQFBXBBPLGIKAK-UHFFFAOYSA-N 0.000 description 3
• 231100000252 nontoxic Toxicity 0.000 description 3
• 230000003000 nontoxic effect Effects 0.000 description 3
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 3
• 239000003755 preservative agent Substances 0.000 description 3
• 229940002612 prodrug Drugs 0.000 description 3
• 239000000651 prodrug Substances 0.000 description 3
• 108090000623 proteins and genes Proteins 0.000 description 3
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
• 239000000376 reactant Substances 0.000 description 3
• 239000002002 slurry Substances 0.000 description 3
• 239000012265 solid product Substances 0.000 description 3
• 239000007921 spray Substances 0.000 description 3
• 239000000758 substrate Substances 0.000 description 3
• 239000000375 suspending agent Substances 0.000 description 3
• 208000024891 symptom Diseases 0.000 description 3
• 239000003826 tablet Substances 0.000 description 3
• RVFSDZYQOUEGRN-UHFFFAOYSA-N tert-butyl 4-[3-[5-(2-fluoro-4-iodoanilino)-3-[(4-methoxyphenyl)methyl]-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]benzoyl]piperazine-1-carboxylate Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N(C=2C=C(C=CC=2)C(=O)N2CCN(CC2)C(=O)OC(C)(C)C)C1=O RVFSDZYQOUEGRN-UHFFFAOYSA-N 0.000 description 3
• NLSIIVXUOYNXBR-UHFFFAOYSA-N tert-butyl n-[3-(azetidine-1-carbonyl)phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CC(C(=O)N2CCC2)=C1 NLSIIVXUOYNXBR-UHFFFAOYSA-N 0.000 description 3
• RIHFOMQQWZOEPU-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-(3-nitrophenyl)methanone Chemical compound [O-][N+](=O)C1=CC=CC(C(=O)N2CCS(=O)(=O)CC2)=C1 RIHFOMQQWZOEPU-UHFFFAOYSA-N 0.000 description 2
• IEADKAMTZQWDAR-IBGZPJMESA-N (2s)-2-[3-[5-(2-fluoro-4-iodoanilino)-3,6,8-trimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]-2-hydroxyacetamide Chemical compound O=C1N(C)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C1=CC=CC([C@H](O)C(N)=O)=C1 IEADKAMTZQWDAR-IBGZPJMESA-N 0.000 description 2
• ZULOTYWZYPALJU-UHFFFAOYSA-N (3-aminophenyl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=CC=CC(N)=C1 ZULOTYWZYPALJU-UHFFFAOYSA-N 0.000 description 2
• DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 2
• 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 description 2
• 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 2
• PSJZUOQEJLFBJL-UHFFFAOYSA-N 1-[3-[3-cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]cyclopropane-1-carboxamide Chemical compound O=C1N(C2CC2)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1C1(C(N)=O)CC1 PSJZUOQEJLFBJL-UHFFFAOYSA-N 0.000 description 2
• RFVPLCQAOXKITI-UHFFFAOYSA-N 1-[3-[5-(2-fluoro-4-iodoanilino)-3,6,8-trimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]cyclopropane-1-carboxamide Chemical compound Cc1c2n(-c3cccc(c3)C3(CC3)C(N)=O)c(=O)n(C)c(=O)c2c(Nc2ccc(I)cc2F)n(C)c1=O RFVPLCQAOXKITI-UHFFFAOYSA-N 0.000 description 2
• XDOFQFKRPWOURC-UHFFFAOYSA-N 16-methylheptadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-N 0.000 description 2
• DVARSTKIISHCDR-UHFFFAOYSA-N 2-(3-nitrophenyl)-n-(oxetan-3-yl)acetamide Chemical compound [O-][N+](=O)C1=CC=CC(CC(=O)NC2COC2)=C1 DVARSTKIISHCDR-UHFFFAOYSA-N 0.000 description 2
• WAVKEPUFQMUGBP-UHFFFAOYSA-N 2-(3-nitrophenyl)acetonitrile Chemical compound [O-][N+](=O)C1=CC=CC(CC#N)=C1 WAVKEPUFQMUGBP-UHFFFAOYSA-N 0.000 description 2
• ZJLCDLCSJVHJTK-UHFFFAOYSA-N 2-[1-[3-(cyclopropylcarbamoyl)phenyl]-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-3-yl]acetic acid Chemical compound O=C1N(CC(O)=O)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1C(=O)NC1CC1 ZJLCDLCSJVHJTK-UHFFFAOYSA-N 0.000 description 2
• AJHPGXZOIAYYDW-UHFFFAOYSA-N 3-(2-cyanophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)NC(C(O)=O)CC1=CC=CC=C1C#N AJHPGXZOIAYYDW-UHFFFAOYSA-N 0.000 description 2
• ZNDYLPPLFKNPDU-UHFFFAOYSA-N 3-(3-aminophenyl)-2-methylpropanamide Chemical compound NC(=O)C(C)CC1=CC=CC(N)=C1 ZNDYLPPLFKNPDU-UHFFFAOYSA-N 0.000 description 2
• SAPAUOFSCLCQJB-UHFFFAOYSA-N 3-[(2-methylpropan-2-yl)oxycarbonylamino]benzoic acid Chemical compound CC(C)(C)OC(=O)NC1=CC=CC(C(O)=O)=C1 SAPAUOFSCLCQJB-UHFFFAOYSA-N 0.000 description 2
• GHGMFLOYYMTSBZ-UHFFFAOYSA-N 3-[5-(2-fluoro-4-iodoanilino)-3,6,8-trimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]-n-(oxan-4-yl)benzamide Chemical compound O=C1N(C)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1C(=O)NC1CCOCC1 GHGMFLOYYMTSBZ-UHFFFAOYSA-N 0.000 description 2
• ACBQYJBCUHLLFR-UHFFFAOYSA-N 3-amino-n-[1-(hydroxymethyl)cyclopropyl]benzamide Chemical compound NC1=CC=CC(C(=O)NC2(CO)CC2)=C1 ACBQYJBCUHLLFR-UHFFFAOYSA-N 0.000 description 2
• RTZZCYNQPHTPPL-UHFFFAOYSA-N 3-nitrophenol Chemical compound OC1=CC=CC([N+]([O-])=O)=C1 RTZZCYNQPHTPPL-UHFFFAOYSA-N 0.000 description 2
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
• 208000024827 Alzheimer disease Diseases 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
• 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 2
• 241000283690 Bos taurus Species 0.000 description 2
• 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 description 2
• 208000006029 Cardiomegaly Diseases 0.000 description 2
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 2
• 229920002261 Corn starch Polymers 0.000 description 2
• HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 2
• 201000003883 Cystic fibrosis Diseases 0.000 description 2
• 206010012689 Diabetic retinopathy Diseases 0.000 description 2
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
• IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 2
• 108091008794 FGF receptors Proteins 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• 208000010412 Glaucoma Diseases 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• 239000007821 HATU Substances 0.000 description 2
• 206010019280 Heart failures Diseases 0.000 description 2
• 206010019842 Hepatomegaly Diseases 0.000 description 2
• 208000017604 Hodgkin disease Diseases 0.000 description 2
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
• 229940124647 MEK inhibitor Drugs 0.000 description 2
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 2
• 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 2
• 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 239000004698 Polyethylene Substances 0.000 description 2
• ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
• 208000004403 Prostatic Hyperplasia Diseases 0.000 description 2
• 108010089836 Proto-Oncogene Proteins c-met Proteins 0.000 description 2
• 102000008022 Proto-Oncogene Proteins c-met Human genes 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
• 206010039491 Sarcoma Diseases 0.000 description 2
• 206010040070 Septic Shock Diseases 0.000 description 2
• 235000021355 Stearic acid Nutrition 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
• 206010049060 Vascular Graft Occlusion Diseases 0.000 description 2
• RCCOZJPSLZNDFV-UHFFFAOYSA-N [3-cyclopropyl-1-(2-fluoro-4-iodophenyl)-6,8-dimethyl-2,4,7-trioxopyrido[2,3-d]pyrimidin-5-yl] 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC1=C(C)C(=O)N(C)C2=C1C(=O)N(C1CC1)C(=O)N2C1=CC=C(I)C=C1F RCCOZJPSLZNDFV-UHFFFAOYSA-N 0.000 description 2
• 230000003213 activating effect Effects 0.000 description 2
• ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 2
• 150000001298 alcohols Chemical class 0.000 description 2
• 125000002723 alicyclic group Chemical group 0.000 description 2
• 229910052783 alkali metal Inorganic materials 0.000 description 2
• 150000001340 alkali metals Chemical class 0.000 description 2
• 238000003016 alphascreen Methods 0.000 description 2
• 229910021529 ammonia Inorganic materials 0.000 description 2
• VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 2
• 238000010171 animal model Methods 0.000 description 2
• 125000000129 anionic group Chemical group 0.000 description 2
• 230000001093 anti-cancer Effects 0.000 description 2
• 239000002260 anti-inflammatory agent Substances 0.000 description 2
• 229940121363 anti-inflammatory agent Drugs 0.000 description 2
• 230000006907 apoptotic process Effects 0.000 description 2
• 208000006673 asthma Diseases 0.000 description 2
• HGQULGDOROIPJN-UHFFFAOYSA-N azetidin-1-ium;chloride Chemical compound Cl.C1CNC1 HGQULGDOROIPJN-UHFFFAOYSA-N 0.000 description 2
• 210000004556 brain Anatomy 0.000 description 2
• 210000000481 breast Anatomy 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
• 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 2
• 230000001684 chronic effect Effects 0.000 description 2
• 210000001072 colon Anatomy 0.000 description 2
• 239000008120 corn starch Substances 0.000 description 2
• 229940099112 cornstarch Drugs 0.000 description 2
• 230000008878 coupling Effects 0.000 description 2
• 238000010168 coupling process Methods 0.000 description 2
• 238000005859 coupling reaction Methods 0.000 description 2
• 239000013058 crude material Substances 0.000 description 2
• 239000010779 crude oil Substances 0.000 description 2
• JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
• DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 2
• 230000003247 decreasing effect Effects 0.000 description 2
• 206010012601 diabetes mellitus Diseases 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 238000001035 drying Methods 0.000 description 2
• 239000003995 emulsifying agent Substances 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• MQVAGGADAFIGIR-UHFFFAOYSA-N ethyl 2-[1-[3-(cyclopropylcarbamoyl)phenyl]-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-3-yl]acetate Chemical compound C12=C(C)C(=O)N(C)C(NC=3C(=CC(I)=CC=3)F)=C2C(=O)N(CC(=O)OCC)C(=O)N1C(C=1)=CC=CC=1C(=O)NC1CC1 MQVAGGADAFIGIR-UHFFFAOYSA-N 0.000 description 2
• 239000000796 flavoring agent Substances 0.000 description 2
• 238000001640 fractional crystallisation Methods 0.000 description 2
• 239000000499 gel Substances 0.000 description 2
• 125000005456 glyceride group Chemical group 0.000 description 2
• 235000011187 glycerol Nutrition 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 125000005842 heteroatom Chemical group 0.000 description 2
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
• 239000005556 hormone Substances 0.000 description 2
• 229940088597 hormone Drugs 0.000 description 2
• CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 2
• 230000003463 hyperproliferative effect Effects 0.000 description 2
• 125000005945 imidazopyridyl group Chemical group 0.000 description 2
• 238000011065 in-situ storage Methods 0.000 description 2
• 230000004968 inflammatory condition Effects 0.000 description 2
• 239000004615 ingredient Substances 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 230000000302 ischemic effect Effects 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
• 239000007937 lozenge Substances 0.000 description 2
• 208000002780 macular degeneration Diseases 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 230000014759 maintenance of location Effects 0.000 description 2
• 239000000463 material Substances 0.000 description 2
• 230000009401 metastasis Effects 0.000 description 2
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
• 229940050176 methyl chloride Drugs 0.000 description 2
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• OZWSHHDVJBHDMQ-UHFFFAOYSA-N n-cyclopropyl-3-[3-(2,3-dihydroxypropyl)-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]benzamide Chemical compound O=C1N(CC(O)CO)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1C(=O)NC1CC1 OZWSHHDVJBHDMQ-UHFFFAOYSA-N 0.000 description 2
• 201000003142 neovascular glaucoma Diseases 0.000 description 2
• BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical compound CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 2
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
• JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 2
• 235000021313 oleic acid Nutrition 0.000 description 2
• OJEOJUQOECNDND-UHFFFAOYSA-N oxetan-3-amine Chemical compound NC1COC1 OJEOJUQOECNDND-UHFFFAOYSA-N 0.000 description 2
• 229910052760 oxygen Inorganic materials 0.000 description 2
• 238000007911 parenteral administration Methods 0.000 description 2
• 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 2
• VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
• 239000008180 pharmaceutical surfactant Substances 0.000 description 2
• 229920000573 polyethylene Polymers 0.000 description 2
• 229920001184 polypeptide Polymers 0.000 description 2
• 239000000843 powder Substances 0.000 description 2
• 102000004196 processed proteins & peptides Human genes 0.000 description 2
• 108090000765 processed proteins & peptides Proteins 0.000 description 2
• 238000011321 prophylaxis Methods 0.000 description 2
• 108010077182 raf Kinases Proteins 0.000 description 2
• 102000009929 raf Kinases Human genes 0.000 description 2
• 102000005962 receptors Human genes 0.000 description 2
• 230000002829 reductive effect Effects 0.000 description 2
• 208000004644 retinal vein occlusion Diseases 0.000 description 2
• 238000012552 review Methods 0.000 description 2
• 125000006413 ring segment Chemical group 0.000 description 2
• 238000000926 separation method Methods 0.000 description 2
• 230000036303 septic shock Effects 0.000 description 2
• 230000019491 signal transduction Effects 0.000 description 2
• 230000011664 signaling Effects 0.000 description 2
• 239000000344 soap Substances 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 239000008117 stearic acid Substances 0.000 description 2
• 230000000707 stereoselective effect Effects 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• ZMZDMBWJUHKJPS-UHFFFAOYSA-N thiocyanic acid Chemical compound SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 2
• 210000001519 tissue Anatomy 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
• JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
• XFNUTZWASODOQK-UHFFFAOYSA-N (1-ethoxycarbonylcyclopropyl)azanium;chloride Chemical compound Cl.CCOC(=O)C1(N)CC1 XFNUTZWASODOQK-UHFFFAOYSA-N 0.000 description 1
• FNHHVPPSBFQMEL-KQHDFZBMSA-N (3S)-5-N-[(1S,5R)-3-hydroxy-6-bicyclo[3.1.0]hexanyl]-7-N,3-dimethyl-3-phenyl-2H-1-benzofuran-5,7-dicarboxamide Chemical compound CNC(=O)c1cc(cc2c1OC[C@@]2(C)c1ccccc1)C(=O)NC1[C@H]2CC(O)C[C@@H]12 FNHHVPPSBFQMEL-KQHDFZBMSA-N 0.000 description 1
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
• ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
• 125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
• PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
• 125000005871 1,3-benzodioxolyl group Chemical group 0.000 description 1
• IGERFAHWSHDDHX-UHFFFAOYSA-N 1,3-dioxanyl Chemical group [CH]1OCCCO1 IGERFAHWSHDDHX-UHFFFAOYSA-N 0.000 description 1
• JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 description 1
• ILWJAOPQHOZXAN-UHFFFAOYSA-N 1,3-dithianyl Chemical group [CH]1SCCCS1 ILWJAOPQHOZXAN-UHFFFAOYSA-N 0.000 description 1
• FLOJNXXFMHCMMR-UHFFFAOYSA-N 1,3-dithiolanyl Chemical group [CH]1SCCS1 FLOJNXXFMHCMMR-UHFFFAOYSA-N 0.000 description 1
• OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
• JLGZOQPEHPQEGW-UHFFFAOYSA-N 1-(2-fluoro-4-iodophenyl)-5-hydroxy-3-[(4-methoxyphenyl)methyl]-6,8-dimethylpyrido[2,3-d]pyrimidine-2,4,7-trione Chemical compound C1=CC(OC)=CC=C1CN1C(=O)C(C(O)=C(C)C(=O)N2C)=C2N(C=2C(=CC(I)=CC=2)F)C1=O JLGZOQPEHPQEGW-UHFFFAOYSA-N 0.000 description 1
• HHSJKTOTRCJLBB-UHFFFAOYSA-N 1-(3-nitrobenzoyl)piperidin-4-one Chemical compound [O-][N+](=O)C1=CC=CC(C(=O)N2CCC(=O)CC2)=C1 HHSJKTOTRCJLBB-UHFFFAOYSA-N 0.000 description 1
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
• PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
• VJWZVOXOTHKSIT-UHFFFAOYSA-N 1-[3-(1,1-dioxo-1,4-thiazinane-4-carbonyl)phenyl]-3-ethyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethylpyrido[4,3-d]pyrimidine-2,4,7-trione Chemical compound C12=C(C)C(=O)N(C)C(NC=3C(=CC(I)=CC=3)F)=C2C(=O)N(CC)C(=O)N1C(C=1)=CC=CC=1C(=O)N1CCS(=O)(=O)CC1 VJWZVOXOTHKSIT-UHFFFAOYSA-N 0.000 description 1
• PSKHHWQROMVLNP-UHFFFAOYSA-N 1-[3-(1,1-dioxo-1,4-thiazinane-4-carbonyl)phenyl]-5-(2-fluoro-4-iodoanilino)-3,6,8-trimethylpyrido[4,3-d]pyrimidine-2,4,7-trione Chemical compound O=C1N(C)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1C(=O)N1CCS(=O)(=O)CC1 PSKHHWQROMVLNP-UHFFFAOYSA-N 0.000 description 1
• YTKCWJTYUNPSKK-UHFFFAOYSA-N 1-[3-(azetidine-1-carbonyl)phenyl]-5-(2-fluoro-4-iodoanilino)-6,8-dimethylpyrido[4,3-d]pyrimidine-2,4,7-trione Chemical compound O=C1NC(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1C(=O)N1CCC1 YTKCWJTYUNPSKK-UHFFFAOYSA-N 0.000 description 1
• QXOGPTXQGKQSJT-UHFFFAOYSA-N 1-amino-4-[4-(3,4-dimethylphenyl)sulfanylanilino]-9,10-dioxoanthracene-2-sulfonic acid Chemical compound Cc1ccc(Sc2ccc(Nc3cc(c(N)c4C(=O)c5ccccc5C(=O)c34)S(O)(=O)=O)cc2)cc1C QXOGPTXQGKQSJT-UHFFFAOYSA-N 0.000 description 1
• STHHLVCQSLRQNI-UHFFFAOYSA-N 1-azabicyclo[3.2.1]octane Chemical compound C1C2CCN1CCC2 STHHLVCQSLRQNI-UHFFFAOYSA-N 0.000 description 1
• FMEHIMDNLRASDU-UHFFFAOYSA-N 1-azabicyclo[3.3.1]nonane Chemical compound C1CCN2CCCC1C2 FMEHIMDNLRASDU-UHFFFAOYSA-N 0.000 description 1
• 125000006083 1-bromoethyl group Chemical group 0.000 description 1
• CBYAZOKPJYBCHE-UHFFFAOYSA-N 1-iodo-3-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC(I)=C1 CBYAZOKPJYBCHE-UHFFFAOYSA-N 0.000 description 1
• 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 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 1
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical group C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
• AFHFSCQVCIFNAK-UHFFFAOYSA-N 2,2-difluoro-2-[3-[5-(2-fluoro-4-iodoanilino)-3,6,8-trimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]acetamide Chemical compound O=C1N(C)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C1=CC=CC(C(F)(F)C(N)=O)=C1 AFHFSCQVCIFNAK-UHFFFAOYSA-N 0.000 description 1
• FQMZXMVHHKXGTM-UHFFFAOYSA-N 2-(1-adamantyl)-n-[2-[2-(2-hydroxyethylamino)ethylamino]quinolin-5-yl]acetamide Chemical compound C1C(C2)CC(C3)CC2CC13CC(=O)NC1=CC=CC2=NC(NCCNCCO)=CC=C21 FQMZXMVHHKXGTM-UHFFFAOYSA-N 0.000 description 1
• LLEZHYGYGJXIGA-UHFFFAOYSA-N 2-[3-[3-cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenoxy]acetamide Chemical compound O=C1N(C2CC2)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C1=CC=CC(OCC(N)=O)=C1 LLEZHYGYGJXIGA-UHFFFAOYSA-N 0.000 description 1
• JLSFSXKUTFKUEA-UHFFFAOYSA-N 2-[3-[3-cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]-2-hydroxyacetamide Chemical compound O=C1N(C2CC2)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C1=CC=CC(C(O)C(N)=O)=C1 JLSFSXKUTFKUEA-UHFFFAOYSA-N 0.000 description 1
• AGFOZVJTIURBSE-UHFFFAOYSA-N 2-[3-[3-cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]-2-methylpropanamide Chemical compound O=C1N(C2CC2)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C1=CC=CC(C(C)(C)C(N)=O)=C1 AGFOZVJTIURBSE-UHFFFAOYSA-N 0.000 description 1
• GIRFRBSOUPJPLD-UHFFFAOYSA-N 2-[3-[3-cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]-n,n-dimethylacetamide Chemical compound CN(C)C(=O)CC1=CC=CC(N2C(N(C3CC3)C(=O)C3=C(NC=4C(=CC(I)=CC=4)F)N(C)C(=O)C(C)=C32)=O)=C1 GIRFRBSOUPJPLD-UHFFFAOYSA-N 0.000 description 1
• CAYUJKOZHBYJFW-UHFFFAOYSA-N 2-[3-[3-cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]-n-(oxetan-3-yl)acetamide Chemical compound O=C1N(C2CC2)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1CC(=O)NC1COC1 CAYUJKOZHBYJFW-UHFFFAOYSA-N 0.000 description 1
• WQDORPCLUMGDDI-UHFFFAOYSA-N 2-[3-[3-cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]acetamide Chemical compound O=C1N(C2CC2)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C1=CC=CC(CC(N)=O)=C1 WQDORPCLUMGDDI-UHFFFAOYSA-N 0.000 description 1
• XBPRVKXOWPNCMK-UHFFFAOYSA-N 2-[3-[5-(2-fluoro-4-iodoanilino)-3,6,8-trimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenoxy]acetamide Chemical compound O=C1N(C)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C1=CC=CC(OCC(N)=O)=C1 XBPRVKXOWPNCMK-UHFFFAOYSA-N 0.000 description 1
• MJCYXNIQTWAPQZ-UHFFFAOYSA-N 2-[3-[5-(2-fluoro-4-iodoanilino)-3,6,8-trimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]-2-methylpropanamide Chemical compound O=C1N(C)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C1=CC=CC(C(C)(C)C(N)=O)=C1 MJCYXNIQTWAPQZ-UHFFFAOYSA-N 0.000 description 1
• AJQRMCVUYKYYLZ-UHFFFAOYSA-N 2-[3-[5-(2-fluoro-4-iodoanilino)-3,6,8-trimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]-n-(oxetan-3-yl)acetamide Chemical compound O=C1N(C)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1CC(=O)NC1COC1 AJQRMCVUYKYYLZ-UHFFFAOYSA-N 0.000 description 1
• WIGZAQRVXQATCF-UHFFFAOYSA-N 2-[3-[5-(2-fluoro-4-iodoanilino)-3,6,8-trimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]acetamide Chemical compound O=C1N(C)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C1=CC=CC(CC(N)=O)=C1 WIGZAQRVXQATCF-UHFFFAOYSA-N 0.000 description 1
• MFQNNHMUKURFPY-UHFFFAOYSA-N 2-[3-[5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenoxy]-2-methylpropanamide Chemical compound O=C1NC(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C1=CC=CC(OC(C)(C)C(N)=O)=C1 MFQNNHMUKURFPY-UHFFFAOYSA-N 0.000 description 1
• LRBNICQRLLCDOF-UHFFFAOYSA-N 2-[3-[5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenoxy]acetamide Chemical compound O=C1NC(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C1=CC=CC(OCC(N)=O)=C1 LRBNICQRLLCDOF-UHFFFAOYSA-N 0.000 description 1
• JSFFSBHSJSJWOA-UHFFFAOYSA-N 2-[3-[5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]-2-hydroxyacetamide Chemical compound O=C1NC(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C1=CC=CC(C(O)C(N)=O)=C1 JSFFSBHSJSJWOA-UHFFFAOYSA-N 0.000 description 1
• LQBCOPPWNLLSKU-UHFFFAOYSA-N 2-[3-[5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]-n,n-dimethylacetamide Chemical compound CN(C)C(=O)CC1=CC=CC(N2C(NC(=O)C3=C(NC=4C(=CC(I)=CC=4)F)N(C)C(=O)C(C)=C32)=O)=C1 LQBCOPPWNLLSKU-UHFFFAOYSA-N 0.000 description 1
• LVTOBSIBSNKUGA-UHFFFAOYSA-N 2-[3-[5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-3-(oxetan-3-yl)-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenoxy]acetamide Chemical compound O=C1N(C2COC2)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C1=CC=CC(OCC(N)=O)=C1 LVTOBSIBSNKUGA-UHFFFAOYSA-N 0.000 description 1
• ZPWIVSGEQGESFF-UHFFFAOYSA-N 2-chloro-n-cyclopropylacetamide Chemical compound ClCC(=O)NC1CC1 ZPWIVSGEQGESFF-UHFFFAOYSA-N 0.000 description 1
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
• VMJVILHBTARYCM-UHFFFAOYSA-N 3-(3-aminophenyl)-n-cyclopropylpropanamide Chemical compound NC1=CC=CC(CCC(=O)NC2CC2)=C1 VMJVILHBTARYCM-UHFFFAOYSA-N 0.000 description 1
• POBPZATWDRHOQA-UHFFFAOYSA-N 3-(3-aminophenyl)-n-methylpropanamide Chemical compound CNC(=O)CCC1=CC=CC(N)=C1 POBPZATWDRHOQA-UHFFFAOYSA-N 0.000 description 1
• QCYCUIGAICOZNN-UHFFFAOYSA-N 3-(3-aminophenyl)propanamide Chemical compound NC(=O)CCC1=CC=CC(N)=C1 QCYCUIGAICOZNN-UHFFFAOYSA-N 0.000 description 1
• SBHFVSXLYOBZKD-UHFFFAOYSA-N 3-(3-aminophenyl)propanoic acid Chemical compound NC1=CC=CC(CCC(O)=O)=C1 SBHFVSXLYOBZKD-UHFFFAOYSA-N 0.000 description 1
• PBQAYGIVDIQLPJ-UHFFFAOYSA-N 3-[3-[3-cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]-n-methylpropanamide Chemical compound CNC(=O)CCC1=CC=CC(N2C(N(C3CC3)C(=O)C3=C(NC=4C(=CC(I)=CC=4)F)N(C)C(=O)C(C)=C32)=O)=C1 PBQAYGIVDIQLPJ-UHFFFAOYSA-N 0.000 description 1
• XKUPAOFNAAEWCW-UHFFFAOYSA-N 3-[3-[3-cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]propanamide Chemical compound O=C1N(C2CC2)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C1=CC=CC(CCC(N)=O)=C1 XKUPAOFNAAEWCW-UHFFFAOYSA-N 0.000 description 1
• WRDFVUZRVYQEHU-UHFFFAOYSA-N 3-[3-[3-ethyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]propanamide Chemical compound C12=C(C)C(=O)N(C)C(NC=3C(=CC(I)=CC=3)F)=C2C(=O)N(CC)C(=O)N1C1=CC=CC(CCC(N)=O)=C1 WRDFVUZRVYQEHU-UHFFFAOYSA-N 0.000 description 1
• KKZCTWAKXHDMSH-UHFFFAOYSA-N 3-[3-[5-(2-fluoro-4-iodoanilino)-3,6,8-trimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]propanamide Chemical compound O=C1N(C)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C1=CC=CC(CCC(N)=O)=C1 KKZCTWAKXHDMSH-UHFFFAOYSA-N 0.000 description 1
• JTVHYQKBKOUBKB-UHFFFAOYSA-N 3-[3-[5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]-n-methylpropanamide Chemical compound CNC(=O)CCC1=CC=CC(N2C(NC(=O)C3=C(NC=4C(=CC(I)=CC=4)F)N(C)C(=O)C(C)=C32)=O)=C1 JTVHYQKBKOUBKB-UHFFFAOYSA-N 0.000 description 1
• WAVDMBPLHCKMOF-UHFFFAOYSA-N 3-[5-(2-fluoro-4-iodoanilino)-3,6,8-trimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]-n-(oxetan-3-yl)benzamide Chemical compound O=C1N(C)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1C(=O)NC1COC1 WAVDMBPLHCKMOF-UHFFFAOYSA-N 0.000 description 1
• BPECBJDBKVLGCF-UHFFFAOYSA-N 3-[5-(2-fluoro-4-iodoanilino)-3,6,8-trimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]-n-(oxolan-3-yl)benzamide Chemical compound O=C1N(C)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1C(=O)NC1CCOC1 BPECBJDBKVLGCF-UHFFFAOYSA-N 0.000 description 1
• LGGYDWKFDIIGMY-UHFFFAOYSA-N 3-[5-(2-fluoro-4-iodoanilino)-3,6,8-trimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]-n-[1-(hydroxymethyl)cyclopropyl]benzamide Chemical compound O=C1N(C)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1C(=O)NC1(CO)CC1 LGGYDWKFDIIGMY-UHFFFAOYSA-N 0.000 description 1
• FSXATRGTACWPRZ-UHFFFAOYSA-N 3-[5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]-n-(oxan-4-yl)benzamide Chemical compound O=C1NC(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1C(=O)NC1CCOCC1 FSXATRGTACWPRZ-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• XBVHCCQAIJOLIT-UHFFFAOYSA-N 3-cyclopropyl-1-[3-(1,1-dioxo-1,3-thiazolidine-3-carbonyl)phenyl]-5-(2-fluoro-4-iodoanilino)-6,8-dimethylpyrido[4,3-d]pyrimidine-2,4,7-trione Chemical compound O=C1N(C2CC2)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1C(=O)N1CCS(=O)(=O)C1 XBVHCCQAIJOLIT-UHFFFAOYSA-N 0.000 description 1
• KJBIMWPRTMIVFN-UHFFFAOYSA-N 3-cyclopropyl-1-[3-(1,1-dioxo-1,4-thiazinane-4-carbonyl)phenyl]-5-(2-fluoro-4-iodoanilino)-6,8-dimethylpyrido[4,3-d]pyrimidine-2,4,7-trione Chemical compound O=C1N(C2CC2)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1C(=O)N1CCS(=O)(=O)CC1 KJBIMWPRTMIVFN-UHFFFAOYSA-N 0.000 description 1
• ZETIVVHRRQLWFW-UHFFFAOYSA-N 3-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC(C=O)=C1 ZETIVVHRRQLWFW-UHFFFAOYSA-N 0.000 description 1
• OKHTXMYUDWHGOC-UHFFFAOYSA-N 4-(3-chlorophenyl)butan-2-one Chemical compound CC(=O)CCC1=CC=CC(Cl)=C1 OKHTXMYUDWHGOC-UHFFFAOYSA-N 0.000 description 1
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
• HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 1
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
• 208000002008 AIDS-Related Lymphoma Diseases 0.000 description 1
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
• 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• 208000007860 Anus Neoplasms Diseases 0.000 description 1
• 235000017060 Arachis glabrata Nutrition 0.000 description 1
• 244000105624 Arachis hypogaea Species 0.000 description 1
• 235000010777 Arachis hypogaea Nutrition 0.000 description 1
• 235000018262 Arachis monticola Nutrition 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
• 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 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
• 238000010152 Bonferroni least significant difference Methods 0.000 description 1
• 208000011691 Burkitt lymphomas Diseases 0.000 description 1
• 101150041968 CDC13 gene Proteins 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 241000282465 Canis Species 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• 208000005623 Carcinogenesis Diseases 0.000 description 1
• 201000009030 Carcinoma Diseases 0.000 description 1
• 208000020446 Cardiac disease Diseases 0.000 description 1
• 241001466804 Carnivora Species 0.000 description 1
• 229940123587 Cell cycle inhibitor Drugs 0.000 description 1
• 241000282693 Cercopithecidae Species 0.000 description 1
• 206010008342 Cervix carcinoma Diseases 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• 206010009944 Colon cancer Diseases 0.000 description 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
• 229920002785 Croscarmellose sodium Polymers 0.000 description 1
• 229920000858 Cyclodextrin Polymers 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• 230000004544 DNA amplification Effects 0.000 description 1
• 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
• 102100031480 Dual specificity mitogen-activated protein kinase kinase 1 Human genes 0.000 description 1
• 101710146526 Dual specificity mitogen-activated protein kinase kinase 1 Proteins 0.000 description 1
• 102000001301 EGF receptor Human genes 0.000 description 1
• 108060006698 EGF receptor Proteins 0.000 description 1
• LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
• 206010014733 Endometrial cancer Diseases 0.000 description 1
• 206010014759 Endometrial neoplasm Diseases 0.000 description 1
• 206010014967 Ependymoma Diseases 0.000 description 1
• 241000283086 Equidae Species 0.000 description 1
• 241000283073 Equus caballus Species 0.000 description 1
• 241000282324 Felis Species 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 1
• 206010064571 Gene mutation Diseases 0.000 description 1
• 208000031448 Genomic Instability Diseases 0.000 description 1
• 208000032612 Glial tumor Diseases 0.000 description 1
• 206010018338 Glioma Diseases 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• 244000068988 Glycine max Species 0.000 description 1
• 235000010469 Glycine max Nutrition 0.000 description 1
• 108010009202 Growth Factor Receptors Proteins 0.000 description 1
• 102000009465 Growth Factor Receptors Human genes 0.000 description 1
• 229920002907 Guar gum Polymers 0.000 description 1
• 102100022623 Hepatocyte growth factor receptor Human genes 0.000 description 1
• 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
• 241001272567 Hominoidea Species 0.000 description 1
• 101000972946 Homo sapiens Hepatocyte growth factor receptor Proteins 0.000 description 1
• 101001056180 Homo sapiens Induced myeloid leukemia cell differentiation protein Mcl-1 Proteins 0.000 description 1
• 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 1
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical class ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
• 238000012404 In vitro experiment Methods 0.000 description 1
• 102100026539 Induced myeloid leukemia cell differentiation protein Mcl-1 Human genes 0.000 description 1
• 108010002352 Interleukin-1 Proteins 0.000 description 1
• 108090001005 Interleukin-6 Proteins 0.000 description 1
• 206010061252 Intraocular melanoma Diseases 0.000 description 1
• 208000007766 Kaposi sarcoma Diseases 0.000 description 1
• 208000002260 Keloid Diseases 0.000 description 1
• 208000008839 Kidney Neoplasms Diseases 0.000 description 1
• 239000005511 L01XE05 - Sorafenib Substances 0.000 description 1
• 241000283953 Lagomorpha Species 0.000 description 1
• 239000012448 Lithium borohydride Substances 0.000 description 1
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
• 206010025312 Lymphoma AIDS related Diseases 0.000 description 1
• 206010025323 Lymphomas Diseases 0.000 description 1
• 102000019149 MAP kinase activity proteins Human genes 0.000 description 1
• 108040008097 MAP kinase activity proteins Proteins 0.000 description 1
• 102000043136 MAP kinase family Human genes 0.000 description 1
• 108091054455 MAP kinase family Proteins 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 208000000172 Medulloblastoma Diseases 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 241000699666 Mus <mouse, genus> Species 0.000 description 1
• 101100381978 Mus musculus Braf gene Proteins 0.000 description 1
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
• LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 1
• 239000007832 Na2SO4 Substances 0.000 description 1
• 208000012902 Nervous system disease Diseases 0.000 description 1
• 208000009277 Neuroectodermal Tumors Diseases 0.000 description 1
• 208000025966 Neurological disease Diseases 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
• 240000007817 Olea europaea Species 0.000 description 1
• 239000005642 Oleic acid Substances 0.000 description 1
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
• 206010031096 Oropharyngeal cancer Diseases 0.000 description 1
• 206010057444 Oropharyngeal neoplasm Diseases 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 206010033128 Ovarian cancer Diseases 0.000 description 1
• 206010061535 Ovarian neoplasm Diseases 0.000 description 1
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
• 239000004264 Petrolatum Substances 0.000 description 1
• 208000007641 Pinealoma Diseases 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
• 241000288906 Primates Species 0.000 description 1
• GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
• 206010060862 Prostate cancer Diseases 0.000 description 1
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
• 208000015634 Rectal Neoplasms Diseases 0.000 description 1
• 208000006265 Renal cell carcinoma Diseases 0.000 description 1
• 201000000582 Retinoblastoma Diseases 0.000 description 1
• 241000283984 Rodentia Species 0.000 description 1
• 208000004337 Salivary Gland Neoplasms Diseases 0.000 description 1
• LDEBVRIURYMKQS-WISUUJSJSA-N Ser-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@@H](N)CO LDEBVRIURYMKQS-WISUUJSJSA-N 0.000 description 1
• 244000000231 Sesamum indicum Species 0.000 description 1
• 235000003434 Sesamum indicum Nutrition 0.000 description 1
• 208000000453 Skin Neoplasms Diseases 0.000 description 1
• 208000021712 Soft tissue sarcoma Diseases 0.000 description 1
• 229920002125 Sokalan® Polymers 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 241000282887 Suidae Species 0.000 description 1
• 241001493546 Suina Species 0.000 description 1
• ULUAUXLGCMPNKK-UHFFFAOYSA-N Sulfobutanedioic acid Chemical class OC(=O)CC(C(O)=O)S(O)(=O)=O ULUAUXLGCMPNKK-UHFFFAOYSA-N 0.000 description 1
• 241000282898 Sus scrofa Species 0.000 description 1
• 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 description 1
• 208000024313 Testicular Neoplasms Diseases 0.000 description 1
• 206010057644 Testis cancer Diseases 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• 102000040945 Transcription factor Human genes 0.000 description 1
• 108091023040 Transcription factor Proteins 0.000 description 1
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
• GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical class OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
• 239000005703 Trimethylamine hydrochloride Substances 0.000 description 1
• 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
• 201000005969 Uveal melanoma Diseases 0.000 description 1
• 206010047741 Vulval cancer Diseases 0.000 description 1
• 208000004354 Vulvar Neoplasms Diseases 0.000 description 1
• 240000008042 Zea mays Species 0.000 description 1
• 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
• 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
• CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 1
• WLLIXJBWWFGEHT-UHFFFAOYSA-N [tert-butyl(dimethyl)silyl] trifluoromethanesulfonate Chemical compound CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F WLLIXJBWWFGEHT-UHFFFAOYSA-N 0.000 description 1
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
• 125000004442 acylamino group Chemical group 0.000 description 1
• 125000004423 acyloxy group Chemical group 0.000 description 1
• 238000011374 additional therapy Methods 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 125000001931 aliphatic group Chemical group 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 150000001342 alkaline earth metals Chemical class 0.000 description 1
• 150000001336 alkenes Chemical class 0.000 description 1
• 125000003282 alkyl amino group Chemical group 0.000 description 1
• 239000002168 alkylating agent Substances 0.000 description 1
• 229940100198 alkylating agent Drugs 0.000 description 1
• 230000003281 allosteric effect Effects 0.000 description 1
• 230000004075 alteration Effects 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 239000004037 angiogenesis inhibitor Substances 0.000 description 1
• 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
• 230000003388 anti-hormonal effect Effects 0.000 description 1
• 230000000340 anti-metabolite Effects 0.000 description 1
• 239000002256 antimetabolite Substances 0.000 description 1
• 229940100197 antimetabolite Drugs 0.000 description 1
• 239000003080 antimitotic agent Substances 0.000 description 1
• 239000002246 antineoplastic agent Substances 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 239000008346 aqueous phase Substances 0.000 description 1
• 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
• 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
• 150000007860 aryl ester derivatives Chemical class 0.000 description 1
• 238000011717 athymic nude mouse Methods 0.000 description 1
• 125000004429 atom Chemical group 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 description 1
• CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
• 125000003725 azepanyl group Chemical group 0.000 description 1
• UQUPQEUNHVVNKW-UHFFFAOYSA-N azetidin-1-ium-3-ol;chloride Chemical compound Cl.OC1CNC1 UQUPQEUNHVVNKW-UHFFFAOYSA-N 0.000 description 1
• 125000004069 aziridinyl group Chemical group 0.000 description 1
• 125000003828 azulenyl group Chemical group 0.000 description 1
• 108010056708 bcr-abl Fusion Proteins Proteins 0.000 description 1
• 102000004441 bcr-abl Fusion Proteins Human genes 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000005874 benzothiadiazolyl group Chemical group 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
• GPRLTFBKWDERLU-UHFFFAOYSA-N bicyclo[2.2.2]octane Chemical group C1CC2CCC1CC2 GPRLTFBKWDERLU-UHFFFAOYSA-N 0.000 description 1
• JAPMJSVZDUYFKL-UHFFFAOYSA-N bicyclo[3.1.0]hexane Chemical group C1CCC2CC21 JAPMJSVZDUYFKL-UHFFFAOYSA-N 0.000 description 1
• SHOMMGQAMRXRRK-UHFFFAOYSA-N bicyclo[3.1.1]heptane Chemical group C1C2CC1CCC2 SHOMMGQAMRXRRK-UHFFFAOYSA-N 0.000 description 1
• AWYMFBJJKFTCFO-UHFFFAOYSA-N bicyclo[3.2.0]heptane Chemical class C1CCC2CCC21 AWYMFBJJKFTCFO-UHFFFAOYSA-N 0.000 description 1
• GNTFBMAGLFYMMZ-UHFFFAOYSA-N bicyclo[3.2.2]nonane Chemical group C1CC2CCC1CCC2 GNTFBMAGLFYMMZ-UHFFFAOYSA-N 0.000 description 1
• WNTGVOIBBXFMLR-UHFFFAOYSA-N bicyclo[3.3.1]nonane Chemical group C1CCC2CCCC1C2 WNTGVOIBBXFMLR-UHFFFAOYSA-N 0.000 description 1
• WMRPOCDOMSNXCQ-UHFFFAOYSA-N bicyclo[3.3.2]decane Chemical group C1CCC2CCCC1CC2 WMRPOCDOMSNXCQ-UHFFFAOYSA-N 0.000 description 1
• KVLCIHRZDOKRLK-UHFFFAOYSA-N bicyclo[4.2.1]nonane Chemical group C1C2CCC1CCCC2 KVLCIHRZDOKRLK-UHFFFAOYSA-N 0.000 description 1
• ACWZRVQXLIRSDF-UHFFFAOYSA-N binimetinib Chemical compound OCCONC(=O)C=1C=C2N(C)C=NC2=C(F)C=1NC1=CC=C(Br)C=C1F ACWZRVQXLIRSDF-UHFFFAOYSA-N 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 239000006172 buffering agent Substances 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 229910000024 caesium carbonate Inorganic materials 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 235000011010 calcium phosphates Nutrition 0.000 description 1
• CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
• 235000013539 calcium stearate Nutrition 0.000 description 1
• 239000008116 calcium stearate Substances 0.000 description 1
• 238000004364 calculation method Methods 0.000 description 1
• 230000036952 cancer formation Effects 0.000 description 1
• 229910021386 carbon form Inorganic materials 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 125000002843 carboxylic acid group Chemical group 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 231100000504 carcinogenesis Toxicity 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 239000004359 castor oil Substances 0.000 description 1
• 235000019438 castor oil Nutrition 0.000 description 1
• 239000003054 catalyst Substances 0.000 description 1
• 125000002091 cationic group Chemical group 0.000 description 1
• 230000030833 cell death Effects 0.000 description 1
• 230000010261 cell growth Effects 0.000 description 1
• 230000036978 cell physiology Effects 0.000 description 1
• 239000006285 cell suspension Substances 0.000 description 1
• 230000006567 cellular energy metabolism Effects 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• 201000010881 cervical cancer Diseases 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 238000002512 chemotherapy Methods 0.000 description 1
• 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
• 208000006990 cholangiocarcinoma Diseases 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
• 238000003776 cleavage reaction Methods 0.000 description 1
• 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
• 208000029742 colonic neoplasm Diseases 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000009833 condensation Methods 0.000 description 1
• 230000005494 condensation Effects 0.000 description 1
• 238000010276 construction Methods 0.000 description 1
• 235000005822 corn Nutrition 0.000 description 1
• 235000012343 cottonseed oil Nutrition 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 229960001681 croscarmellose sodium Drugs 0.000 description 1
• 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
• 201000007241 cutaneous T cell lymphoma Diseases 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 229940127089 cytotoxic agent Drugs 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• 230000037430 deletion Effects 0.000 description 1
• 238000012217 deletion Methods 0.000 description 1
• 238000010511 deprotection reaction Methods 0.000 description 1
• 230000001627 detrimental effect Effects 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 125000005959 diazepanyl group Chemical group 0.000 description 1
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
• 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
• 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
• XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
• IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
• 208000037765 diseases and disorders Diseases 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
• 239000012636 effector Substances 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• 239000002532 enzyme inhibitor 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
• 150000002170 ethers Chemical class 0.000 description 1
• 229940052303 ethers for general anesthesia Drugs 0.000 description 1
• IRSJDVYTJUCXRV-UHFFFAOYSA-N ethyl 2-bromo-2,2-difluoroacetate Chemical compound CCOC(=O)C(F)(F)Br IRSJDVYTJUCXRV-UHFFFAOYSA-N 0.000 description 1
• IOLQWGVDEFWYNP-UHFFFAOYSA-N ethyl 2-bromo-2-methylpropanoate Chemical compound CCOC(=O)C(C)(C)Br IOLQWGVDEFWYNP-UHFFFAOYSA-N 0.000 description 1
• RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
• 125000004494 ethyl ester group Chemical group 0.000 description 1
• LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
• 229940093471 ethyl oleate Drugs 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 102000052178 fibroblast growth factor receptor activity proteins Human genes 0.000 description 1
• 230000001842 fibrogenetic effect Effects 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 235000019634 flavors Nutrition 0.000 description 1
• 239000012530 fluid Substances 0.000 description 1
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 239000006260 foam Substances 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 235000019253 formic acid Nutrition 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 230000002496 gastric effect Effects 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 230000014509 gene expression Effects 0.000 description 1
• 238000007429 general method Methods 0.000 description 1
• ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
• 150000002334 glycols Chemical class 0.000 description 1
• 239000000665 guar gum Substances 0.000 description 1
• 235000010417 guar gum Nutrition 0.000 description 1
• 229960002154 guar gum Drugs 0.000 description 1
• 201000009277 hairy cell leukemia Diseases 0.000 description 1
• 210000003128 head Anatomy 0.000 description 1
• 208000019622 heart disease Diseases 0.000 description 1
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
• 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
• 210000003494 hepatocyte Anatomy 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• BNRNAKTVFSZAFA-UHFFFAOYSA-N hydrindane Chemical compound C1CCCC2CCCC21 BNRNAKTVFSZAFA-UHFFFAOYSA-N 0.000 description 1
• 125000001183 hydrocarbyl group Chemical group 0.000 description 1
• 230000003301 hydrolyzing effect Effects 0.000 description 1
• RGZRSLKIOCHTSI-UHFFFAOYSA-N hydron;n-methylhydroxylamine;chloride Chemical compound Cl.CNO RGZRSLKIOCHTSI-UHFFFAOYSA-N 0.000 description 1
• 230000002209 hydrophobic effect Effects 0.000 description 1
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
• UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
• 230000037417 hyperactivation Effects 0.000 description 1
• 206010020718 hyperplasia Diseases 0.000 description 1
• 239000005457 ice water Substances 0.000 description 1
• 125000002632 imidazolidinyl group Chemical group 0.000 description 1
• 125000002636 imidazolinyl group Chemical group 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 239000000367 immunologic factor Substances 0.000 description 1
• 238000001727 in vivo Methods 0.000 description 1
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 230000002757 inflammatory effect Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 238000011221 initial treatment Methods 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 150000007529 inorganic bases Chemical class 0.000 description 1
• 239000000138 intercalating agent Substances 0.000 description 1
• QWXYZCJEXYQNEI-OSZHWHEXSA-N intermediate I Chemical compound COC(=O)[C@@]1(C=O)[C@H]2CC=[N+](C\C2=C\C)CCc2c1[nH]c1ccccc21 QWXYZCJEXYQNEI-OSZHWHEXSA-N 0.000 description 1
• 238000001361 intraarterial administration Methods 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 201000008893 intraocular retinoblastoma Diseases 0.000 description 1
• 230000009545 invasion Effects 0.000 description 1
• 206010073095 invasive ductal breast carcinoma Diseases 0.000 description 1
• 201000010985 invasive ductal carcinoma Diseases 0.000 description 1
• 206010073096 invasive lobular breast carcinoma Diseases 0.000 description 1
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• 208000028867 ischemia Diseases 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
• 125000005969 isothiazolinyl group Chemical group 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 125000003965 isoxazolidinyl group Chemical group 0.000 description 1
• 125000003971 isoxazolinyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 238000005304 joining Methods 0.000 description 1
• 210000001117 keloid Anatomy 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 229960001375 lactose Drugs 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 208000012987 lip and oral cavity carcinoma Diseases 0.000 description 1
• 208000019039 lip and oral cavity squamous cell carcinoma Diseases 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 239000012669 liquid formulation Substances 0.000 description 1
• 239000006193 liquid solution Substances 0.000 description 1
• GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium;hydroxide;hydrate Chemical compound [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 210000003563 lymphoid tissue Anatomy 0.000 description 1
• 208000025036 lymphosarcoma Diseases 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
• 235000019341 magnesium sulphate Nutrition 0.000 description 1
• 238000012423 maintenance Methods 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 230000003211 malignant effect Effects 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 229960001855 mannitol Drugs 0.000 description 1
• 238000004519 manufacturing process Methods 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 210000000716 merkel cell Anatomy 0.000 description 1
• 208000030159 metabolic disease Diseases 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 230000037353 metabolic pathway Effects 0.000 description 1
• WOMSTXBCVBQGKV-UHFFFAOYSA-N methanol;palladium Chemical compound [Pd].OC WOMSTXBCVBQGKV-UHFFFAOYSA-N 0.000 description 1
• VZDNXXPBYLGWOS-UHFFFAOYSA-N methyl 3-aminobenzoate Chemical compound COC(=O)C1=CC=CC(N)=C1 VZDNXXPBYLGWOS-UHFFFAOYSA-N 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 239000003226 mitogen Substances 0.000 description 1
• 208000016044 mixed lobular and ductal breast carcinoma Diseases 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 239000002808 molecular sieve Substances 0.000 description 1
• 125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
• 210000004877 mucosa Anatomy 0.000 description 1
• 201000006417 multiple sclerosis Diseases 0.000 description 1
• 201000005962 mycosis fungoides Diseases 0.000 description 1
• JEPUSDHLXQSNKH-UHFFFAOYSA-N n-(1-carbamoylcyclopropyl)-3-[5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]benzamide Chemical compound O=C1NC(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1C(=O)NC1(C(N)=O)CC1 JEPUSDHLXQSNKH-UHFFFAOYSA-N 0.000 description 1
• YCJZWBZJSYLMPB-UHFFFAOYSA-N n-(2-chloropyrimidin-4-yl)-2,5-dimethyl-1-phenylimidazole-4-carboxamide Chemical compound CC=1N(C=2C=CC=CC=2)C(C)=NC=1C(=O)NC1=CC=NC(Cl)=N1 YCJZWBZJSYLMPB-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• ZJASNLLFWJNHSR-UHFFFAOYSA-N n-cyclopropyl-2-[3-[3-cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenoxy]acetamide Chemical compound O=C1N(C2CC2)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1OCC(=O)NC1CC1 ZJASNLLFWJNHSR-UHFFFAOYSA-N 0.000 description 1
• BWQXIWMHXUKWIE-UHFFFAOYSA-N n-cyclopropyl-2-[3-[3-ethyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]acetamide Chemical compound C12=C(C)C(=O)N(C)C(NC=3C(=CC(I)=CC=3)F)=C2C(=O)N(CC)C(=O)N1C(C=1)=CC=CC=1CC(=O)NC1CC1 BWQXIWMHXUKWIE-UHFFFAOYSA-N 0.000 description 1
• HXMXWDLDJVJDFM-UHFFFAOYSA-N n-cyclopropyl-2-[3-[5-(2-fluoro-4-iodoanilino)-3,6,8-trimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenoxy]acetamide Chemical compound O=C1N(C)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1OCC(=O)NC1CC1 HXMXWDLDJVJDFM-UHFFFAOYSA-N 0.000 description 1
• NXDRXCJNYYLHQC-UHFFFAOYSA-N n-cyclopropyl-2-[3-[5-(2-fluoro-4-iodoanilino)-3,6,8-trimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]acetamide Chemical compound O=C1N(C)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1CC(=O)NC1CC1 NXDRXCJNYYLHQC-UHFFFAOYSA-N 0.000 description 1
• DDBILUUPBOHQFC-UHFFFAOYSA-N n-cyclopropyl-3-[3-[3-cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]propanamide Chemical compound O=C1N(C2CC2)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1CCC(=O)NC1CC1 DDBILUUPBOHQFC-UHFFFAOYSA-N 0.000 description 1
• GZOZATBPLIAXPF-UHFFFAOYSA-N n-cyclopropyl-3-[3-[5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]propanamide Chemical compound O=C1NC(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1CCC(=O)NC1CC1 GZOZATBPLIAXPF-UHFFFAOYSA-N 0.000 description 1
• ABAKQKKZTYHURC-UHFFFAOYSA-N n-cyclopropyl-3-[3-cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]benzamide Chemical compound O=C1N(C2CC2)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1C(=O)NC1CC1 ABAKQKKZTYHURC-UHFFFAOYSA-N 0.000 description 1
• VIIOMUOBDTZSLA-UHFFFAOYSA-N n-cyclopropyl-3-[3-ethyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]benzamide Chemical compound C12=C(C)C(=O)N(C)C(NC=3C(=CC(I)=CC=3)F)=C2C(=O)N(CC)C(=O)N1C(C=1)=CC=CC=1C(=O)NC1CC1 VIIOMUOBDTZSLA-UHFFFAOYSA-N 0.000 description 1
• NJEIKIJJIXTUOF-UHFFFAOYSA-N n-cyclopropyl-3-[5-(2-fluoro-4-iodoanilino)-3,6,8-trimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]benzamide Chemical compound O=C1N(C)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1C(=O)NC1CC1 NJEIKIJJIXTUOF-UHFFFAOYSA-N 0.000 description 1
• HTIUCHCUWODLOF-UHFFFAOYSA-N n-cyclopropyl-3-[5-(2-fluoro-4-iodoanilino)-3-(2-hydroxyethyl)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]benzamide Chemical compound O=C1N(CCO)C(=O)C2=C(NC=3C(=CC(I)=CC=3)F)N(C)C(=O)C(C)=C2N1C(C=1)=CC=CC=1C(=O)NC1CC1 HTIUCHCUWODLOF-UHFFFAOYSA-N 0.000 description 1
• RGCYFLDBQYTSAD-UHFFFAOYSA-N n-cyclopropyl-3-[5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxo-3-propan-2-ylpyrido[4,3-d]pyrimidin-1-yl]benzamide Chemical compound C12=C(C)C(=O)N(C)C(NC=3C(=CC(I)=CC=3)F)=C2C(=O)N(C(C)C)C(=O)N1C(C=1)=CC=CC=1C(=O)NC1CC1 RGCYFLDBQYTSAD-UHFFFAOYSA-N 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 239000006199 nebulizer Substances 0.000 description 1
• 230000006654 negative regulation of apoptotic process Effects 0.000 description 1
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 125000006574 non-aromatic ring group Chemical group 0.000 description 1
• 102000037979 non-receptor tyrosine kinases Human genes 0.000 description 1
• 108091008046 non-receptor tyrosine kinases Proteins 0.000 description 1
• 239000002736 nonionic surfactant Substances 0.000 description 1
• UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical group C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 description 1
• 201000002575 ocular melanoma Diseases 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 150000002889 oleic acids Chemical class 0.000 description 1
• 235000015205 orange juice Nutrition 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 201000006958 oropharynx cancer Diseases 0.000 description 1
• 229910000489 osmium tetroxide Inorganic materials 0.000 description 1
• 201000008968 osteosarcoma Diseases 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 230000002018 overexpression Effects 0.000 description 1
• 125000005963 oxadiazolidinyl group Chemical group 0.000 description 1
• 125000005882 oxadiazolinyl group Chemical group 0.000 description 1
• 125000001715 oxadiazolyl group Chemical group 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• AHVQYHFYQWKUKB-UHFFFAOYSA-N oxan-4-amine Chemical compound NC1CCOCC1 AHVQYHFYQWKUKB-UHFFFAOYSA-N 0.000 description 1
• 125000000160 oxazolidinyl group Chemical group 0.000 description 1
• 125000005968 oxazolinyl group Chemical group 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• MIPHRQMEIYLZFZ-UHFFFAOYSA-N oxolan-3-amine Chemical compound NC1CCOC1 MIPHRQMEIYLZFZ-UHFFFAOYSA-N 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
• 210000000496 pancreas Anatomy 0.000 description 1
• 230000000849 parathyroid Effects 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 239000006072 paste Substances 0.000 description 1
• 235000010603 pastilles Nutrition 0.000 description 1
• 235000020232 peanut Nutrition 0.000 description 1
• 235000010987 pectin Nutrition 0.000 description 1
• 239000001814 pectin Substances 0.000 description 1
• 229920001277 pectin Polymers 0.000 description 1
• 229940066842 petrolatum Drugs 0.000 description 1
• 235000019271 petrolatum Nutrition 0.000 description 1
• 239000003208 petroleum Substances 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
• 230000006461 physiological response Effects 0.000 description 1
• GJQNVZVOTKFLIU-UHFFFAOYSA-N piperidin-1-ium-4-one;chloride Chemical compound Cl.O=C1CCNCC1 GJQNVZVOTKFLIU-UHFFFAOYSA-N 0.000 description 1
• IPOVLZSJBYKHHU-UHFFFAOYSA-N piperidin-3-ylmethanamine Chemical compound NCC1CCCNC1 IPOVLZSJBYKHHU-UHFFFAOYSA-N 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• 239000002798 polar solvent Substances 0.000 description 1
• 229920005606 polypropylene copolymer Polymers 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 235000011181 potassium carbonates Nutrition 0.000 description 1
• 229920001592 potato starch Polymers 0.000 description 1
• 229940116317 potato starch Drugs 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 238000002953 preparative HPLC Methods 0.000 description 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
• 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
• 239000001294 propane Substances 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
• 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
• 125000002755 pyrazolinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• 125000004076 pyridyl group Chemical group 0.000 description 1
• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• QPMSJEFZULFYTB-UHFFFAOYSA-N pyrrolidin-1-ium-3-ol;chloride Chemical compound Cl.OC1CCNC1 QPMSJEFZULFYTB-UHFFFAOYSA-N 0.000 description 1
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• 125000001422 pyrrolinyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• 108700042226 ras Genes Proteins 0.000 description 1
• 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
• 108020003175 receptors Proteins 0.000 description 1
• 230000001850 reproductive effect Effects 0.000 description 1
• 230000008672 reprogramming Effects 0.000 description 1
• 210000002345 respiratory system Anatomy 0.000 description 1
• 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
• 239000012047 saturated solution Substances 0.000 description 1
• HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
• 230000007017 scission Effects 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 230000028327 secretion Effects 0.000 description 1
• 201000000849 skin cancer Diseases 0.000 description 1
• 201000008261 skin carcinoma Diseases 0.000 description 1
• 210000000813 small intestine Anatomy 0.000 description 1
• 201000002314 small intestine cancer Diseases 0.000 description 1
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• 229910000104 sodium hydride Inorganic materials 0.000 description 1
• RNVYQYLELCKWAN-UHFFFAOYSA-N solketal Chemical compound CC1(C)OCC(CO)O1 RNVYQYLELCKWAN-UHFFFAOYSA-N 0.000 description 1
• 229960003787 sorafenib Drugs 0.000 description 1
• 235000011069 sorbitan monooleate Nutrition 0.000 description 1
• 239000001593 sorbitan monooleate Substances 0.000 description 1
• 229940035049 sorbitan monooleate Drugs 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• KADZWYHUUBXOPO-UHFFFAOYSA-N spiro[2,3,3a,4,5,6a-hexahydro-1H-pentalene-6,1'-cyclopropane] Chemical compound C1CC11C2CCCC2CC1 KADZWYHUUBXOPO-UHFFFAOYSA-N 0.000 description 1
• FOEYMRPOKBCNCR-UHFFFAOYSA-N spiro[2.5]octane Chemical compound C1CC11CCCCC1 FOEYMRPOKBCNCR-UHFFFAOYSA-N 0.000 description 1
• MOTHUBJOUGRFPE-UHFFFAOYSA-N spiro[bicyclo[4.1.0]heptane-2,1'-cyclopentane] Chemical compound C12CC2CCCC21CCCC2 MOTHUBJOUGRFPE-UHFFFAOYSA-N 0.000 description 1
• CTDQAGUNKPRERK-UHFFFAOYSA-N spirodecane Chemical compound C1CCCC21CCCCC2 CTDQAGUNKPRERK-UHFFFAOYSA-N 0.000 description 1
• 206010041823 squamous cell carcinoma Diseases 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 238000003756 stirring Methods 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 125000005017 substituted alkenyl group Chemical group 0.000 description 1
• 125000000547 substituted alkyl group Chemical group 0.000 description 1
• 125000003107 substituted aryl group Chemical group 0.000 description 1
• 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• 229960004793 sucrose Drugs 0.000 description 1
• 150000005846 sugar alcohols Polymers 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 230000004654 survival pathway Effects 0.000 description 1
• 230000002459 sustained effect Effects 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• FAGLEPBREOXSAC-UHFFFAOYSA-N tert-butyl isocyanide Chemical compound CC(C)(C)[N+]#[C-] FAGLEPBREOXSAC-UHFFFAOYSA-N 0.000 description 1
• CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
• 201000003120 testicular cancer Diseases 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
• CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 1
• CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 125000005304 thiadiazolidinyl group Chemical group 0.000 description 1
• 125000005305 thiadiazolinyl group Chemical group 0.000 description 1
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• 125000001984 thiazolidinyl group Chemical group 0.000 description 1
• 125000002769 thiazolinyl group Chemical group 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
• 210000001685 thyroid gland Anatomy 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 239000012049 topical pharmaceutical composition Substances 0.000 description 1
• 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• 125000004306 triazinyl group Chemical group 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
• 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
• 230000001960 triggered effect Effects 0.000 description 1
• SZYJELPVAFJOGJ-UHFFFAOYSA-N trimethylamine hydrochloride Chemical compound Cl.CN(C)C SZYJELPVAFJOGJ-UHFFFAOYSA-N 0.000 description 1
• 125000005455 trithianyl group Chemical group 0.000 description 1
• 231100000588 tumorigenic Toxicity 0.000 description 1
• 230000000381 tumorigenic effect Effects 0.000 description 1
• 238000011144 upstream manufacturing Methods 0.000 description 1
• 210000000626 ureter Anatomy 0.000 description 1
• 210000003932 urinary bladder Anatomy 0.000 description 1
• 210000001635 urinary tract Anatomy 0.000 description 1
• 210000004291 uterus Anatomy 0.000 description 1
• 206010046885 vaginal cancer Diseases 0.000 description 1
• 208000013139 vaginal neoplasm Diseases 0.000 description 1
• 235000013311 vegetables Nutrition 0.000 description 1
• 230000035899 viability Effects 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 229920002554 vinyl polymer Polymers 0.000 description 1
• 201000005102 vulva cancer Diseases 0.000 description 1
• 208000012993 vulva sarcoma Diseases 0.000 description 1
• 201000008758 vulvar sarcoma Diseases 0.000 description 1
• 230000003442 weekly effect Effects 0.000 description 1
• 238000010626 work up procedure Methods 0.000 description 1
• 238000013298 xenograft nude mouse model Methods 0.000 description 1
• 239000008096 xylene Substances 0.000 description 1
• 235000005074 zinc chloride Nutrition 0.000 description 1
• 239000011592 zinc chloride Substances 0.000 description 1
• XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1