BR112016014151B1 - Pirirmidopirimidinonas úteis como inibidores de quinases wee-1 - Google Patents

Info

Publication number

BR112016014151B1

BR112016014151B1 BR112016014151-2A BR112016014151A BR112016014151B1 BR 112016014151 B1 BR112016014151 B1 BR 112016014151B1 BR 112016014151 A BR112016014151 A BR 112016014151A BR 112016014151 B1 BR112016014151 B1 BR 112016014151B1

Authority

BR

Brazil

Prior art keywords

methyl

group

amino

pyrimidin

dichlorophenyl

Prior art date

2013-12-19

Links

• Espacenet
• Global Dossier
• Discuss

• 229940043355 kinase inhibitor Drugs 0.000 title abstract description 4
• 239000003757 phosphotransferase inhibitor Substances 0.000 title abstract description 4
• 150000001875 compounds Chemical class 0.000 claims abstract description 469
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 43
• 201000011510 cancer Diseases 0.000 claims abstract description 30
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 14
• -1 2,6-dichlorophenyl group Chemical group 0.000 claims description 122
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 81
• 125000000623 heterocyclic group Chemical group 0.000 claims description 80
• 150000003839 salts Chemical class 0.000 claims description 60
• 125000001072 heteroaryl group Chemical group 0.000 claims description 49
• 125000006413 ring segment Chemical group 0.000 claims description 46
• 125000001424 substituent group Chemical group 0.000 claims description 43
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 39
• 229910052757 nitrogen Inorganic materials 0.000 claims description 36
• 125000003277 amino group Chemical group 0.000 claims description 34
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 32
• 125000005843 halogen group Chemical group 0.000 claims description 31
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 31
• 125000003118 aryl group Chemical group 0.000 claims description 28
• 229910052799 carbon Inorganic materials 0.000 claims description 28
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 28
• 125000003107 substituted aryl group Chemical group 0.000 claims description 26
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 25
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 25
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 24
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
• DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 claims description 22
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 22
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 21
• 229910052805 deuterium Inorganic materials 0.000 claims description 19
• 125000004043 oxo group Chemical group O=* 0.000 claims description 17
• 125000005017 substituted alkenyl group Chemical group 0.000 claims description 16
• PPGWAKHCMDIJCZ-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-(4-piperazin-1-ylanilino)-7h-pyrimido[4,5-d]pyrimidin-5-one Chemical compound N1=C2N(C)CN(C=3C(=CC=CC=3Cl)Cl)C(=O)C2=CN=C1NC(C=C1)=CC=C1N1CCNCC1 PPGWAKHCMDIJCZ-UHFFFAOYSA-N 0.000 claims description 15
• 125000000217 alkyl group Chemical group 0.000 claims description 15
• 125000004432 carbon atom Chemical group C* 0.000 claims description 15
• 239000003814 drug Substances 0.000 claims description 15
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 14
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 11
• 125000004076 pyridyl group Chemical group 0.000 claims description 11
• 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 11
• 125000003342 alkenyl group Chemical group 0.000 claims description 10
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 10
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 10
• 125000005415 substituted alkoxy group Chemical group 0.000 claims description 8
• LBMRQLZAIMKGES-OAHLLOKOSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[4-[(3R)-3-methylpiperazin-1-yl]anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound C[C@@H]1CN(CCN1)C1=CC=C(NC2=NC3=C(C=N2)C(=O)N(CN3C)C2=C(Cl)C=CC=C2Cl)C=C1 LBMRQLZAIMKGES-OAHLLOKOSA-N 0.000 claims description 7
• 125000003545 alkoxy group Chemical group 0.000 claims description 7
• 125000002619 bicyclic group Chemical group 0.000 claims description 7
• 229940079593 drug Drugs 0.000 claims description 7
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 7
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 7
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 6
• QHBLDARXYVRQPT-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-(3-methoxy-4-piperazin-1-ylanilino)-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1CCNCC1)OC)C QHBLDARXYVRQPT-UHFFFAOYSA-N 0.000 claims description 6
• NLEKABKQRTTZQM-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[3-(hydroxymethyl)-4-piperazin-1-ylanilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1CCNCC1)CO)C NLEKABKQRTTZQM-UHFFFAOYSA-N 0.000 claims description 6
• OWGPFTUYSFJYBP-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-[(4-methoxyphenyl)methyl]-2-(4-piperazin-1-ylanilino)-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound COC1=CC=C(CN2CN(C(=O)C3=C2N=C(NC2=CC=C(C=C2)N2CCNCC2)N=C3)C2=C(Cl)C=CC=C2Cl)C=C1 OWGPFTUYSFJYBP-UHFFFAOYSA-N 0.000 claims description 6
• 125000002883 imidazolyl group Chemical group 0.000 claims description 6
• 125000002560 nitrile group Chemical group 0.000 claims description 6
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
• 125000003396 thiol group Chemical group [H]S* 0.000 claims description 6
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 5
• XCCUNKZLGDBUDS-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[3-(methoxymethyl)-4-piperazin-1-ylanilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1CCNCC1)COC)C XCCUNKZLGDBUDS-UHFFFAOYSA-N 0.000 claims description 5
• IUUBRYQHJICSNC-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-7,8-dimethyl-2-(4-piperazin-1-ylanilino)-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1C(N(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1CCNCC1)C)C IUUBRYQHJICSNC-UHFFFAOYSA-N 0.000 claims description 5
• DYMIHMMQKGYANV-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-(1,2,3,4-tetrahydroisoquinolin-7-ylamino)-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C2CCNCC2=C1)C DYMIHMMQKGYANV-UHFFFAOYSA-N 0.000 claims description 5
• FAIFKBRNZILADG-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[3-(methylaminomethyl)-4-morpholin-4-ylanilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound CNCC1=C(C=CC(NC2=NC3=C(C=N2)C(=O)N(CN3C)C2=C(Cl)C=CC=C2Cl)=C1)N1CCOCC1 FAIFKBRNZILADG-UHFFFAOYSA-N 0.000 claims description 5
• XLLRCHIYUAZPPN-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-7-phenyl-2-(1,2,3,4-tetrahydroisoquinolin-7-ylamino)-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1C(N(C2=NC(=NC=C2C1=O)NC1=CC=C2CCNCC2=C1)C)C1=CC=CC=C1 XLLRCHIYUAZPPN-UHFFFAOYSA-N 0.000 claims description 5
• QZRCPZQLJJSRKH-UHFFFAOYSA-N 6-(2-chloro-6-fluorophenyl)-8-methyl-2-(4-piperazin-1-ylanilino)-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)F)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1CCNCC1)C QZRCPZQLJJSRKH-UHFFFAOYSA-N 0.000 claims description 5
• GUZWVFYIVMRFIK-UHFFFAOYSA-N 6-(2-chlorophenyl)-8-methyl-2-(4-piperazin-1-ylanilino)-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C=CC=C1)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1CCNCC1)C GUZWVFYIVMRFIK-UHFFFAOYSA-N 0.000 claims description 5
• 125000001931 aliphatic group Chemical group 0.000 claims description 5
• 238000004519 manufacturing process Methods 0.000 claims description 5
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 5
• 125000002971 oxazolyl group Chemical group 0.000 claims description 5
• 125000000335 thiazolyl group Chemical group 0.000 claims description 5
• PPGWAKHCMDIJCZ-FNHLFAINSA-N 2,2-dideuterio-3-(2,6-dichlorophenyl)-1-methyl-7-(4-piperazin-1-ylanilino)pyrimido[4,5-d]pyrimidin-4-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1C(N(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1CCNCC1)C)([2H])[2H] PPGWAKHCMDIJCZ-FNHLFAINSA-N 0.000 claims description 4
• GPODLJVUNGVXNJ-UHFFFAOYSA-N 2-[4-(3,8-diazabicyclo[3.2.1]octan-3-yl)anilino]-6-(2,6-dichlorophenyl)-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound C12CN(CC(CC1)N2)C1=CC=C(C=C1)NC1=NC=C2C(=N1)N(CN(C2=O)C1=C(C=CC=C1Cl)Cl)C GPODLJVUNGVXNJ-UHFFFAOYSA-N 0.000 claims description 4
• ZLUXROJDIBWCSL-UHFFFAOYSA-N 5-[[6-(2,6-dichlorophenyl)-8-methyl-5-oxo-7H-pyrimido[4,5-d]pyrimidin-2-yl]amino]-2-piperazin-1-ylbenzonitrile Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1CCNCC1)C#N)C ZLUXROJDIBWCSL-UHFFFAOYSA-N 0.000 claims description 4
• WMNTUWBEVOCCIL-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-(3-fluoro-4-piperazin-1-ylanilino)-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1CCNCC1)F)C WMNTUWBEVOCCIL-UHFFFAOYSA-N 0.000 claims description 4
• RERWAFRPAAIWBP-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[3-(hydroxymethyl)-4-morpholin-4-ylanilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1CCOCC1)CO)C RERWAFRPAAIWBP-UHFFFAOYSA-N 0.000 claims description 4
• KVQJFGGAQBGGCB-MRXNPFEDSA-N 6-(2,6-dichlorophenyl)-2-[3-(methoxymethyl)-4-[(3R)-3-methylpiperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1C[C@H](NCC1)C)COC)C KVQJFGGAQBGGCB-MRXNPFEDSA-N 0.000 claims description 4
• ZOKGXCGRFOEAGH-CQSZACIVSA-N 6-(2,6-dichlorophenyl)-2-[3-fluoro-4-[(3R)-3-methylpiperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1C[C@H](NCC1)C)F)C ZOKGXCGRFOEAGH-CQSZACIVSA-N 0.000 claims description 4
• IUGRQCZGRNMZFV-MRXNPFEDSA-N 6-(2,6-dichlorophenyl)-2-[4-[(3R)-3-(hydroxymethyl)piperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound CN1CN(C(=O)C2=C1N=C(NC1=CC=C(C=C1)N1CCN[C@@H](CO)C1)N=C2)C1=C(Cl)C=CC=C1Cl IUGRQCZGRNMZFV-MRXNPFEDSA-N 0.000 claims description 4
• IUGRQCZGRNMZFV-INIZCTEOSA-N 6-(2,6-dichlorophenyl)-2-[4-[(3S)-3-(hydroxymethyl)piperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound CN1CN(C(=O)C2=C1N=C(NC1=CC=C(C=C1)N1CCN[C@H](CO)C1)N=C2)C1=C(Cl)C=CC=C1Cl IUGRQCZGRNMZFV-INIZCTEOSA-N 0.000 claims description 4
• YBKOSBVNEDJVHU-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-(3-methyl-4-piperazin-1-ylanilino)-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1CCNCC1)C)C YBKOSBVNEDJVHU-UHFFFAOYSA-N 0.000 claims description 4
• UPIOGLZAQYJLSI-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-(3-methyl-4-piperidin-4-ylanilino)-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound CN1CN(C(=O)C2=C1N=C(NC1=CC(C)=C(C=C1)C1CCNCC1)N=C2)C1=C(Cl)C=CC=C1Cl UPIOGLZAQYJLSI-UHFFFAOYSA-N 0.000 claims description 4
• DQPLNKURCKBGJN-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-(4-piperidin-4-ylanilino)-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)C1CCNCC1)C DQPLNKURCKBGJN-UHFFFAOYSA-N 0.000 claims description 4
• GGNKWWBHXGLGIF-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[(2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)amino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C2CCN(CC2=C1)C)C GGNKWWBHXGLGIF-UHFFFAOYSA-N 0.000 claims description 4
• WIBUEQHFXZMHSQ-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[4-(3-oxa-7,9-diazabicyclo[3.3.1]nonan-7-yl)anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound C12COCC(CN(C1)C1=CC=C(C=C1)NC1=NC=C3C(=N1)N(CN(C3=O)C1=C(C=CC=C1Cl)Cl)C)N2 WIBUEQHFXZMHSQ-UHFFFAOYSA-N 0.000 claims description 4
• MHMOUKLUMPQOEV-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[4-(piperazin-1-ylmethyl)anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)CN1CCNCC1)C MHMOUKLUMPQOEV-UHFFFAOYSA-N 0.000 claims description 4
• LBMRQLZAIMKGES-HNNXBMFYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[4-[(3S)-3-methylpiperazin-1-yl]anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound C[C@H]1CN(CCN1)C1=CC=C(NC2=NC3=C(C=N2)C(=O)N(CN3C)C2=C(Cl)C=CC=C2Cl)C=C1 LBMRQLZAIMKGES-HNNXBMFYSA-N 0.000 claims description 4
• GBTFLFHQAMXZJU-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[4-[2-(methylamino)ethoxy]anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)OCCNC)C GBTFLFHQAMXZJU-UHFFFAOYSA-N 0.000 claims description 4
• LMZQNYTZDCZDNB-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[4-[3-(trifluoromethyl)piperazin-1-yl]anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1CC(NCC1)C(F)(F)F)C LMZQNYTZDCZDNB-UHFFFAOYSA-N 0.000 claims description 4
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 4
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
• 125000002757 morpholinyl group Chemical group 0.000 claims description 4
• 125000003386 piperidinyl group Chemical group 0.000 claims description 4
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
• 229910052717 sulfur Inorganic materials 0.000 claims description 4
• 125000001425 triazolyl group Chemical group 0.000 claims description 4
• LDOSAWKNXJBSTE-UHFFFAOYSA-N 2-[4-(2,6-diazaspiro[3.3]heptan-2-yl)anilino]-6-(2,6-dichlorophenyl)-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound C1N(CC11CNC1)C1=CC=C(C=C1)NC1=NC=C2C(=N1)N(CN(C2=O)C1=C(C=CC=C1Cl)Cl)C LDOSAWKNXJBSTE-UHFFFAOYSA-N 0.000 claims description 3
• ZYBNOUONCCPKEN-UHFFFAOYSA-N 2-[4-(4-acetylpiperazin-1-yl)-3-(methylaminomethyl)anilino]-6-(2,6-dichlorophenyl)-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound C(C)(=O)N1CCN(CC1)C1=C(C=C(C=C1)NC1=NC=C2C(=N1)N(CN(C2=O)C1=C(C=CC=C1Cl)Cl)C)CNC ZYBNOUONCCPKEN-UHFFFAOYSA-N 0.000 claims description 3
• RSZDSSUZZYDOFU-RDJZCZTQSA-N 2-[4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]anilino]-6-(2,6-dichlorophenyl)-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound CN1CN(C(=O)c2cnc(Nc3ccc(cc3)N3C[C@@H]4C[C@H]3CN4)nc12)c1c(Cl)cccc1Cl RSZDSSUZZYDOFU-RDJZCZTQSA-N 0.000 claims description 3
• TXSMTMZSKXXHFO-UHFFFAOYSA-N 2-[4-[4-(2-aminoacetyl)piperazin-1-yl]anilino]-6-(2,6-dichlorophenyl)-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound NCC(=O)N1CCN(CC1)C1=CC=C(C=C1)NC1=NC=C2C(=N1)N(CN(C2=O)C1=C(C=CC=C1Cl)Cl)C TXSMTMZSKXXHFO-UHFFFAOYSA-N 0.000 claims description 3
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 3
• SAVKMENYJBWNHC-CQSZACIVSA-N 6-(2,6-dichlorophenyl)-2-[2-fluoro-4-[(3R)-3-methylpiperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=C(C=C(C=C1)N1C[C@H](NCC1)C)F)C SAVKMENYJBWNHC-CQSZACIVSA-N 0.000 claims description 3
• QJQUTIICTMGERH-MRXNPFEDSA-N 6-(2,6-dichlorophenyl)-2-[3-(2-hydroxypropan-2-yl)-4-[(3R)-3-methylpiperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1C[C@H](NCC1)C)C(C)(C)O)C QJQUTIICTMGERH-MRXNPFEDSA-N 0.000 claims description 3
• HTARTRPLSPTEPQ-CQSZACIVSA-N 6-(2,6-dichlorophenyl)-2-[3-(difluoromethoxy)-4-[(3R)-3-methylpiperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1C[C@H](NCC1)C)OC(F)F)C HTARTRPLSPTEPQ-CQSZACIVSA-N 0.000 claims description 3
• RSLQXUFQMFRUAK-CQSZACIVSA-N 6-(2,6-dichlorophenyl)-2-[3-(difluoromethyl)-4-[(3R)-3-methylpiperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1C[C@H](NCC1)C)C(F)F)C RSLQXUFQMFRUAK-CQSZACIVSA-N 0.000 claims description 3
• UFIXLFHFBVKERS-OAHLLOKOSA-N 6-(2,6-dichlorophenyl)-2-[3-(hydroxymethyl)-4-[(3R)-3-methylpiperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1C[C@H](NCC1)C)CO)C UFIXLFHFBVKERS-OAHLLOKOSA-N 0.000 claims description 3
• VLSTVCLRRXOTDJ-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[3-(hydroxymethyl)-4-piperidin-1-ylanilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1CCCCC1)CO)C VLSTVCLRRXOTDJ-UHFFFAOYSA-N 0.000 claims description 3
• AZJPOVYLWJNKEO-HNNXBMFYSA-N 6-(2,6-dichlorophenyl)-2-[3-fluoro-4-[(3S)-3-(hydroxymethyl)piperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1C[C@H](NCC1)CO)F)C AZJPOVYLWJNKEO-HNNXBMFYSA-N 0.000 claims description 3
• AXGDTZSVROQZDF-LSDHHAIUSA-N 6-(2,6-dichlorophenyl)-2-[4-[(2R,5S)-2,5-dimethylpiperazin-1-yl]-3-fluoroanilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1[C@@H](CN[C@H](C1)C)C)F)C AXGDTZSVROQZDF-LSDHHAIUSA-N 0.000 claims description 3
• GMEKDCLQLMKYFQ-JKSUJKDBSA-N 6-(2,6-dichlorophenyl)-2-[4-[(2R,5S)-2,5-dimethylpiperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1[C@@H](CN[C@H](C1)C)C)C GMEKDCLQLMKYFQ-JKSUJKDBSA-N 0.000 claims description 3
• ZFBXHAQPRJKCAF-KRWDZBQOSA-N 6-(2,6-dichlorophenyl)-2-[4-[(2S)-2-(hydroxymethyl)piperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1[C@@H](CNCC1)CO)C ZFBXHAQPRJKCAF-KRWDZBQOSA-N 0.000 claims description 3
• KUKFNHWJTHJNND-QGZVFWFLSA-N 6-(2,6-dichlorophenyl)-2-[4-[(3R)-3-(methoxymethyl)piperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1C[C@@H](NCC1)COC)C KUKFNHWJTHJNND-QGZVFWFLSA-N 0.000 claims description 3
• IXALLEROHFSSQQ-QGZVFWFLSA-N 6-(2,6-dichlorophenyl)-2-[4-[(3R)-3-methylpiperazin-1-yl]anilino]-8-(1-methylpyrazol-3-yl)-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1C[C@H](NCC1)C)C1=NN(C=C1)C IXALLEROHFSSQQ-QGZVFWFLSA-N 0.000 claims description 3
• SWSGSQSHDZNOAH-IYBDPMFKSA-N 6-(2,6-dichlorophenyl)-2-[4-[(3R,5S)-3,5-dimethylpiperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1C[C@H](N[C@H](C1)C)C)C SWSGSQSHDZNOAH-IYBDPMFKSA-N 0.000 claims description 3
• KUKFNHWJTHJNND-KRWDZBQOSA-N 6-(2,6-dichlorophenyl)-2-[4-[(3S)-3-(methoxymethyl)piperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1C[C@H](NCC1)COC)C KUKFNHWJTHJNND-KRWDZBQOSA-N 0.000 claims description 3
• MNKSIPFQQMPRHB-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-(4-piperidin-4-yloxyanilino)-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)OC1CCNCC1)C MNKSIPFQQMPRHB-UHFFFAOYSA-N 0.000 claims description 3
• DPOQVNWOLCFUBQ-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[3-(methylaminomethyl)-4-piperidin-1-ylanilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1CCCCC1)CNC)C DPOQVNWOLCFUBQ-UHFFFAOYSA-N 0.000 claims description 3
• DYYQQULCKMONHD-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[3-(methylaminomethyl)-4-pyrrolidin-1-ylanilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1CCCC1)CNC)C DYYQQULCKMONHD-UHFFFAOYSA-N 0.000 claims description 3
• UNJUAQURXQZLDK-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[3-[(1-methylpiperidin-4-yl)amino]anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=CC=C1)NC1CCN(CC1)C)C UNJUAQURXQZLDK-UHFFFAOYSA-N 0.000 claims description 3
• HJONQAVNWCAHNQ-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[4-(3,3,4-trimethylpiperazin-1-yl)anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1CC(N(CC1)C)(C)C)C HJONQAVNWCAHNQ-UHFFFAOYSA-N 0.000 claims description 3
• AQBHPKLYVXTHIW-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[4-(4-methylpiperazin-1-yl)anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1CCN(CC1)C)C AQBHPKLYVXTHIW-UHFFFAOYSA-N 0.000 claims description 3
• ZZMUGJXRVBUPIZ-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[4-(methylsulfonimidoyl)anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)S(=O)(=N)C)C ZZMUGJXRVBUPIZ-UHFFFAOYSA-N 0.000 claims description 3
• QZJJZINNSZRIHM-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[4-[(4-methylpiperazin-1-yl)methyl]anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)CN1CCN(CC1)C)C QZJJZINNSZRIHM-UHFFFAOYSA-N 0.000 claims description 3
• QZMIDEVJDLRNSL-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[4-[4-[2-(methylamino)acetyl]piperazin-1-yl]anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1CCN(CC1)C(CNC)=O)C QZMIDEVJDLRNSL-UHFFFAOYSA-N 0.000 claims description 3
• PIUTZCHAHKDSNS-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[4-piperazin-1-yl-3-[(2,2,2-trifluoroethylamino)methyl]anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1CCNCC1)CNCC(F)(F)F)C PIUTZCHAHKDSNS-UHFFFAOYSA-N 0.000 claims description 3
• JGOGTWLPOCEHCA-UHFFFAOYSA-N 6-(2-chloro-6-fluorophenyl)-8-methyl-2-(3-methyl-4-piperazin-1-ylanilino)-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)F)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1CCNCC1)C)C JGOGTWLPOCEHCA-UHFFFAOYSA-N 0.000 claims description 3
• BGTZOHXPSXDVGR-UHFFFAOYSA-N 6-(2-chloro-6-methylphenyl)-2-[3-(hydroxymethyl)-4-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)C)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1CC2CCC(C1)N2C)CO)C BGTZOHXPSXDVGR-UHFFFAOYSA-N 0.000 claims description 3
• FNJSLWWEORZUCG-ZWKOTPCHSA-N 6-(2-chloro-6-methylphenyl)-2-[4-[(2R,5S)-2,5-dimethylpiperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)C)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1[C@@H](CN[C@H](C1)C)C)C FNJSLWWEORZUCG-ZWKOTPCHSA-N 0.000 claims description 3
• MIQLLQJUZWYPPF-UHFFFAOYSA-N 6-(2-chloro-6-methylphenyl)-8-methyl-2-(4-piperazin-1-ylanilino)-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)C)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1CCNCC1)C MIQLLQJUZWYPPF-UHFFFAOYSA-N 0.000 claims description 3
• POSRJPWGGBESEB-UHFFFAOYSA-N 6-(2-chlorophenyl)-2-[3-(hydroxymethyl)-4-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C=CC=C1)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1CC2CCC(C1)N2C)CO)C POSRJPWGGBESEB-UHFFFAOYSA-N 0.000 claims description 3
• BIKGADCMMLSLDY-JKSUJKDBSA-N 6-(2-chlorophenyl)-2-[4-[(2R,5S)-2,5-dimethylpiperazin-1-yl]-3-fluoroanilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C=CC=C1)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1[C@@H](CN[C@H](C1)C)C)F)C BIKGADCMMLSLDY-JKSUJKDBSA-N 0.000 claims description 3
• NPGKJNHXBDJTQI-MRXNPFEDSA-N 6-(2-chlorophenyl)-8-methyl-2-[4-[(3R)-3-methylpiperazin-1-yl]anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C=CC=C1)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1C[C@H](NCC1)C)C NPGKJNHXBDJTQI-MRXNPFEDSA-N 0.000 claims description 3
• NDCHXEIOJINREZ-MRXNPFEDSA-N 8-cyclopropyl-6-(2,6-dichlorophenyl)-2-[4-[(3R)-3-methylpiperazin-1-yl]anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound C1(CC1)N1CN(C(C=2C1=NC(=NC=2)NC1=CC=C(C=C1)N1C[C@H](NCC1)C)=O)C1=C(C=CC=C1Cl)Cl NDCHXEIOJINREZ-MRXNPFEDSA-N 0.000 claims description 3
• 241001465754 Metazoa Species 0.000 claims description 3
• 125000002393 azetidinyl group Chemical group 0.000 claims description 3
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
• 125000004434 sulfur atom Chemical group 0.000 claims description 3
• 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 3
• ZLUTULCSXWROMX-UHFFFAOYSA-N 2-[4-(4-acetylpiperazin-1-yl)-3-(pyrrolidin-1-ylmethyl)anilino]-6-(2,6-dichlorophenyl)-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound C(C)(=O)N1CCN(CC1)C1=C(C=C(C=C1)NC1=NC=C2C(=N1)N(CN(C2=O)C1=C(C=CC=C1Cl)Cl)C)CN1CCCC1 ZLUTULCSXWROMX-UHFFFAOYSA-N 0.000 claims description 2
• HLQQNCRDOLFGLW-UHFFFAOYSA-N 2-[4-(4-acetylpiperazin-1-yl)-3-[(dimethylamino)methyl]anilino]-6-(2,6-dichlorophenyl)-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound C(C)(=O)N1CCN(CC1)C1=C(C=C(C=C1)NC1=NC=C2C(=N1)N(CN(C2=O)C1=C(C=CC=C1Cl)Cl)C)CN(C)C HLQQNCRDOLFGLW-UHFFFAOYSA-N 0.000 claims description 2
• FTSTXKGYDQGDFO-UHFFFAOYSA-N 2-[4-(4-cyclopropylpiperazin-1-yl)anilino]-6-(2,6-dichlorophenyl)-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound C1(CC1)N1CCN(CC1)C1=CC=C(C=C1)NC1=NC=C2C(=N1)N(CN(C2=O)C1=C(C=CC=C1Cl)Cl)C FTSTXKGYDQGDFO-UHFFFAOYSA-N 0.000 claims description 2
• ZDZWFQQAICCRME-IAGOWNOFSA-N 2-[4-[(1R,4R)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-3-methylanilino]-6-(2,6-dichlorophenyl)-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound [C@H]12N(C[C@H](NC1)C2)C1=C(C=C(C=C1)NC1=NC=C2C(=N1)N(CN(C2=O)C1=C(C=CC=C1Cl)Cl)C)C ZDZWFQQAICCRME-IAGOWNOFSA-N 0.000 claims description 2
• ZDZWFQQAICCRME-IRXDYDNUSA-N 2-[4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-3-methylanilino]-6-(2,6-dichlorophenyl)-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound CN1CN(C(=O)c2cnc(Nc3ccc(N4C[C@@H]5C[C@H]4CN5)c(C)c3)nc12)c1c(Cl)cccc1Cl ZDZWFQQAICCRME-IRXDYDNUSA-N 0.000 claims description 2
• SAZDTUOVUDPTJS-IBGZPJMESA-N 2-[4-[(9aS)-3,4,6,7,9,9a-hexahydro-1H-pyrazino[2,1-c][1,4]oxazin-8-yl]-3-(hydroxymethyl)anilino]-6-(2,6-dichlorophenyl)-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1C[C@H]2COCCN2CC1)CO)C SAZDTUOVUDPTJS-IBGZPJMESA-N 0.000 claims description 2
• YYGGNHOXGSACEE-HNNQXCQYSA-N 6-(2,6-dichlorophenyl)-2-[3-(2,2-difluoro-1-hydroxyethyl)-4-[(3R)-3-methylpiperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1C[C@H](NCC1)C)C(C(F)F)O)C YYGGNHOXGSACEE-HNNQXCQYSA-N 0.000 claims description 2
• QLFLZMARLZNPCW-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[3-(hydroxymethyl)-4-(4-propan-2-ylpiperazin-1-yl)anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1CCN(CC1)C(C)C)CO)C QLFLZMARLZNPCW-UHFFFAOYSA-N 0.000 claims description 2
• LUYCBKWHYHGSMI-GOSISDBHSA-N 6-(2,6-dichlorophenyl)-2-[3-(hydroxymethyl)-4-[(3R)-3-(methoxymethyl)piperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1C[C@@H](NCC1)COC)CO)C LUYCBKWHYHGSMI-GOSISDBHSA-N 0.000 claims description 2
• YMNSERAHLLNYNE-INIZCTEOSA-N 6-(2,6-dichlorophenyl)-2-[3-fluoro-4-[(3S)-3-(hydroxymethyl)-4-methylpiperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1C[C@H](N(CC1)C)CO)F)C YMNSERAHLLNYNE-INIZCTEOSA-N 0.000 claims description 2
• KMQLDJJMLMAAJT-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[4-(3,3-dimethylpiperazin-1-yl)anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1CC(NCC1)(C)C)C KMQLDJJMLMAAJT-UHFFFAOYSA-N 0.000 claims description 2
• HBOJJBPKOUDXCN-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[4-(4-ethylpiperazin-1-yl)anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1CCN(CC1)CC)C HBOJJBPKOUDXCN-UHFFFAOYSA-N 0.000 claims description 2
• TURCTQHFIOYSDV-GOSISDBHSA-N 6-(2,6-dichlorophenyl)-2-[4-[(2R)-2-(methoxymethyl)piperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1[C@H](CNCC1)COC)C TURCTQHFIOYSDV-GOSISDBHSA-N 0.000 claims description 2
• GMEKDCLQLMKYFQ-HZPDHXFCSA-N 6-(2,6-dichlorophenyl)-2-[4-[(2R,5R)-2,5-dimethylpiperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1[C@@H](CN[C@@H](C1)C)C)C GMEKDCLQLMKYFQ-HZPDHXFCSA-N 0.000 claims description 2
• TURCTQHFIOYSDV-SFHVURJKSA-N 6-(2,6-dichlorophenyl)-2-[4-[(2S)-2-(methoxymethyl)piperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1[C@@H](CNCC1)COC)C TURCTQHFIOYSDV-SFHVURJKSA-N 0.000 claims description 2
• GMEKDCLQLMKYFQ-CVEARBPZSA-N 6-(2,6-dichlorophenyl)-2-[4-[(2S,5R)-2,5-dimethylpiperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1[C@H](CN[C@@H](C1)C)C)C GMEKDCLQLMKYFQ-CVEARBPZSA-N 0.000 claims description 2
• OZUWIOFAAUEPGS-MRXNPFEDSA-N 6-(2,6-dichlorophenyl)-2-[4-[(3R)-3,4-dimethylpiperazin-1-yl]-3-(hydroxymethyl)anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1C[C@H](N(CC1)C)C)CO)C OZUWIOFAAUEPGS-MRXNPFEDSA-N 0.000 claims description 2
• GSHAKRLADGSLOQ-OAHLLOKOSA-N 6-(2,6-dichlorophenyl)-2-[4-[(3R)-3,4-dimethylpiperazin-1-yl]-3-fluoroanilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1C[C@H](N(CC1)C)C)F)C GSHAKRLADGSLOQ-OAHLLOKOSA-N 0.000 claims description 2
• SMTWXSMNZNWQFB-GOSISDBHSA-N 6-(2,6-dichlorophenyl)-2-[4-[(3R)-3-(hydroxymethyl)-4-methylpiperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1C[C@@H](N(CC1)C)CO)C SMTWXSMNZNWQFB-GOSISDBHSA-N 0.000 claims description 2
• UYYPGHQREGFGNL-LJQANCHMSA-N 6-(2,6-dichlorophenyl)-2-[4-[(3R)-3-(methoxymethyl)-4-methylpiperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1C[C@@H](N(CC1)C)COC)C UYYPGHQREGFGNL-LJQANCHMSA-N 0.000 claims description 2
• UYYPGHQREGFGNL-IBGZPJMESA-N 6-(2,6-dichlorophenyl)-2-[4-[(3S)-3-(methoxymethyl)-4-methylpiperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1C[C@H](N(CC1)C)COC)C UYYPGHQREGFGNL-IBGZPJMESA-N 0.000 claims description 2
• IBMLONZRTOETCO-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[4-[4-(2-hydroxyethyl)piperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1CCN(CC1)CCO)C IBMLONZRTOETCO-UHFFFAOYSA-N 0.000 claims description 2
• OVVPJXTVHVMMDZ-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[4-[4-(2-methoxyethyl)piperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1CCN(CC1)CCOC)C OVVPJXTVHVMMDZ-UHFFFAOYSA-N 0.000 claims description 2
• XMXBHNKQYSXPIQ-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[4-[4-[2-(dimethylamino)acetyl]piperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1CCN(CC1)C(CN(C)C)=O)C XMXBHNKQYSXPIQ-UHFFFAOYSA-N 0.000 claims description 2
• JPQQVBFSTIYAKH-QZTJIDSGSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[3-methyl-4-[(1R,4R)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1[C@H]2CN([C@@H](C1)C2)C)C)C JPQQVBFSTIYAKH-QZTJIDSGSA-N 0.000 claims description 2
• JPQQVBFSTIYAKH-ROUUACIJSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[3-methyl-4-[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1[C@@H]2CN([C@H](C1)C2)C)C)C JPQQVBFSTIYAKH-ROUUACIJSA-N 0.000 claims description 2
• RQRXHKWTOPVAEL-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[4-(1-methylpiperidin-4-yl)anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)C1CCN(CC1)C)C RQRXHKWTOPVAEL-UHFFFAOYSA-N 0.000 claims description 2
• TYNDDJWXWHJULJ-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[4-(1-methylpiperidin-4-yl)oxyanilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)OC1CCN(CC1)C)C TYNDDJWXWHJULJ-UHFFFAOYSA-N 0.000 claims description 2
• QSPBYXZZLJJSDJ-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[4-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1CC2CCC(C1)N2C)C QSPBYXZZLJJSDJ-UHFFFAOYSA-N 0.000 claims description 2
• LOFOCBZJVWJXOF-ROUUACIJSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[4-[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1[C@@H]2CN([C@H](C1)C2)C)C LOFOCBZJVWJXOF-ROUUACIJSA-N 0.000 claims description 2
• QIPWHDRZXZTWDE-DLBZAZTESA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[4-[(2R,5S)-2,4,5-trimethylpiperazin-1-yl]anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1[C@@H](CN([C@H](C1)C)C)C)C QIPWHDRZXZTWDE-DLBZAZTESA-N 0.000 claims description 2
• QYLLIZCJDRQFET-CALCHBBNSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[4-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl]anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1C[C@H](N([C@H](C1)C)C)C)C QYLLIZCJDRQFET-CALCHBBNSA-N 0.000 claims description 2
• LYQRRTLORAKZPC-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[4-[4-methyl-3-(trifluoromethyl)piperazin-1-yl]anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1CC(N(CC1)C)C(F)(F)F)C LYQRRTLORAKZPC-UHFFFAOYSA-N 0.000 claims description 2
• DWZABPWGNXINBZ-RDJZCZTQSA-N 6-(2-chloro-6-fluorophenyl)-2-[4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound CN1CN(C(=O)c2cnc(Nc3ccc(cc3)N3C[C@@H]4C[C@H]3CN4)nc12)c1c(F)cccc1Cl DWZABPWGNXINBZ-RDJZCZTQSA-N 0.000 claims description 2
• XLCOHYCFLXIHIV-JKSUJKDBSA-N 6-(2-chloro-6-fluorophenyl)-2-[4-[(2R,5S)-2,5-dimethylpiperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)F)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1[C@@H](CN[C@H](C1)C)C)C XLCOHYCFLXIHIV-JKSUJKDBSA-N 0.000 claims description 2
• WJXVAXBJYWTBEB-GOSISDBHSA-N 6-(2-chloro-6-methylphenyl)-2-[3-(methoxymethyl)-4-[(3R)-3-methylpiperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)C)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1C[C@H](NCC1)C)COC)C WJXVAXBJYWTBEB-GOSISDBHSA-N 0.000 claims description 2
• LGDNQWAZVHMQCE-OALUTQOASA-N 6-(2-chloro-6-methylphenyl)-2-[4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-3-methylanilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound CN1CN(C(=O)c2cnc(Nc3ccc(N4C[C@@H]5C[C@H]4CN5)c(C)c3)nc12)c1c(C)cccc1Cl LGDNQWAZVHMQCE-OALUTQOASA-N 0.000 claims description 2
• RCIAGFOHBZJAPM-UHFFFAOYSA-N 6-(2-chlorophenyl)-2-[3-(methoxymethyl)-4-piperazin-1-ylanilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C=CC=C1)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1CCNCC1)COC)C RCIAGFOHBZJAPM-UHFFFAOYSA-N 0.000 claims description 2
• SZCJLDNKZMAJKR-UHFFFAOYSA-N 6-(2-chlorophenyl)-2-[4-(3,3-dimethylpiperazin-1-yl)anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C=CC=C1)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1CC(NCC1)(C)C)C SZCJLDNKZMAJKR-UHFFFAOYSA-N 0.000 claims description 2
• MWHZDIRYYSULKI-UHFFFAOYSA-N 6-(2-chlorophenyl)-2-[4-(4-ethylpiperazin-1-yl)-3-(hydroxymethyl)anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C=CC=C1)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1CCN(CC1)CC)CO)C MWHZDIRYYSULKI-UHFFFAOYSA-N 0.000 claims description 2
• KXLUAUGGJKBIJH-IRXDYDNUSA-N 6-(2-chlorophenyl)-2-[4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-3-methoxyanilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound COc1cc(Nc2ncc3C(=O)N(CN(C)c3n2)c2ccccc2Cl)ccc1N1C[C@@H]2C[C@H]1CN2 KXLUAUGGJKBIJH-IRXDYDNUSA-N 0.000 claims description 2
• NFMXSRRNFZGGLX-ROUUACIJSA-N 6-(2-chlorophenyl)-2-[4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-3-methylanilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound CN1CN(C(=O)c2cnc(Nc3ccc(N4C[C@@H]5C[C@H]4CN5)c(C)c3)nc12)c1ccccc1Cl NFMXSRRNFZGGLX-ROUUACIJSA-N 0.000 claims description 2
• PERJRGDWNPTLCF-DLBZAZTESA-N 6-(2-chlorophenyl)-2-[4-[(2R,5S)-2,5-dimethylpiperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C=CC=C1)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1[C@@H](CN[C@H](C1)C)C)C PERJRGDWNPTLCF-DLBZAZTESA-N 0.000 claims description 2
• 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 2
• 125000005505 thiomorpholino group Chemical group 0.000 claims description 2
• 125000004431 deuterium atom Chemical group 0.000 claims 4
• OJPQPKZNJFYQIL-UHFFFAOYSA-N 2-(11-azatricyclo[6.2.1.02,7]undeca-2(7),3,5-trien-4-ylamino)-6-(2,6-dichlorophenyl)-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC=1C=C2C3CCC(C2=CC=1)N3)C OJPQPKZNJFYQIL-UHFFFAOYSA-N 0.000 claims 1
• RMYGRPRYFJVKLB-UHFFFAOYSA-N 2-[4-(1-aminocyclobutyl)anilino]-6-(2,6-dichlorophenyl)-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound NC1(CCC1)C1=CC=C(C=C1)NC1=NC=C2C(=N1)N(CN(C2=O)C1=C(C=CC=C1Cl)Cl)C RMYGRPRYFJVKLB-UHFFFAOYSA-N 0.000 claims 1
• QSMCUHCXSXPJEC-UHFFFAOYSA-N 2-[4-(2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[3,4-c]pyrrol-5-yl)anilino]-6-(2,6-dichlorophenyl)-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1CC2CNCC2C1)C QSMCUHCXSXPJEC-UHFFFAOYSA-N 0.000 claims 1
• GVWNQNHECMZMEG-UHFFFAOYSA-N 2-[4-(4-acetylpiperazin-1-yl)anilino]-6-(2,6-dichlorophenyl)-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound C(C)(=O)N1CCN(CC1)C1=CC=C(C=C1)NC1=NC=C2C(=N1)N(CN(C2=O)C1=C(C=CC=C1Cl)Cl)C GVWNQNHECMZMEG-UHFFFAOYSA-N 0.000 claims 1
• GDXMJOWFEYSQIJ-IRXDYDNUSA-N 2-[4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-3-(hydroxymethyl)anilino]-6-(2,6-dichlorophenyl)-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound CN1CN(C(=O)c2cnc(Nc3ccc(N4C[C@@H]5C[C@H]4CN5)c(CO)c3)nc12)c1c(Cl)cccc1Cl GDXMJOWFEYSQIJ-IRXDYDNUSA-N 0.000 claims 1
• RJMSAQHOZFUOFX-UHFFFAOYSA-N 2-[4-bromo-3-(methylaminomethyl)anilino]-6-(2,6-dichlorophenyl)-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound BrC1=C(C=C(C=C1)NC1=NC=C2C(=N1)N(CN(C2=O)C1=C(C=CC=C1Cl)Cl)C)CNC RJMSAQHOZFUOFX-UHFFFAOYSA-N 0.000 claims 1
• YREZFGSRZATOLT-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-(3-methoxy-4-piperidin-4-ylanilino)-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)C1CCNCC1)OC)C YREZFGSRZATOLT-UHFFFAOYSA-N 0.000 claims 1
• KGMYLTSFAPTXIB-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[3-(ethylaminomethyl)-4-morpholin-4-ylanilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1CCOCC1)CNCC)C KGMYLTSFAPTXIB-UHFFFAOYSA-N 0.000 claims 1
• FSYWYBWCFILSNX-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[3-(hydroxymethyl)-4-(1,2,3,6-tetrahydropyridin-4-yl)anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)C=1CCNCC=1)CO)C FSYWYBWCFILSNX-UHFFFAOYSA-N 0.000 claims 1
• YMXITXZZVGLRFY-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[3-(hydroxymethyl)-4-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)C=1CCN(CC=1)C)CO)C YMXITXZZVGLRFY-UHFFFAOYSA-N 0.000 claims 1
• ICUCQOGIMUELDJ-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[3-(hydroxymethyl)-4-(3-oxa-7,9-diazabicyclo[3.3.1]nonan-7-yl)anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound C12COCC(CN(C1)C1=C(C=C(C=C1)NC1=NC=C3C(=N1)N(CN(C3=O)C1=C(C=CC=C1Cl)Cl)C)CO)N2 ICUCQOGIMUELDJ-UHFFFAOYSA-N 0.000 claims 1
• AIHHGFLJFSDSFZ-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[3-(hydroxymethyl)-4-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1CC2CCC(C1)N2C)CO)C AIHHGFLJFSDSFZ-UHFFFAOYSA-N 0.000 claims 1
• BZJINEFJKOESER-ROUUACIJSA-N 6-(2,6-dichlorophenyl)-2-[3-(hydroxymethyl)-4-[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1[C@@H]2CN([C@H](C1)C2)C)CO)C BZJINEFJKOESER-ROUUACIJSA-N 0.000 claims 1
• RXFFNESXLYNPLX-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[3-(hydroxymethyl)-4-piperidin-4-ylanilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)C1CCNCC1)CO)C RXFFNESXLYNPLX-UHFFFAOYSA-N 0.000 claims 1
• CHJFCELGPFHRBO-WAIKUNEKSA-N 6-(2,6-dichlorophenyl)-2-[3-[(1R)-2,2-difluoro-1-hydroxyethyl]-4-[(3R)-3-(methoxymethyl)piperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1C[C@@H](NCC1)COC)[C@H](C(F)F)O)C CHJFCELGPFHRBO-WAIKUNEKSA-N 0.000 claims 1
• PBMOGRDBNXYTKG-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[3-[(dimethylamino)methyl]-4-(1,1-dioxo-1,4-thiazinan-4-yl)anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1CCS(CC1)(=O)=O)CN(C)C)C PBMOGRDBNXYTKG-UHFFFAOYSA-N 0.000 claims 1
• CPYGWIHTHJOPLM-HDICACEKSA-N 6-(2,6-dichlorophenyl)-2-[3-[(dimethylamino)methyl]-4-[(2R,6S)-2,6-dimethylmorpholin-4-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1C[C@@H](O[C@@H](C1)C)C)CN(C)C)C CPYGWIHTHJOPLM-HDICACEKSA-N 0.000 claims 1
• VDHTVEOKJVXWRR-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[3-[(dimethylamino)methyl]-4-morpholin-4-ylanilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1CCOCC1)CN(C)C)C VDHTVEOKJVXWRR-UHFFFAOYSA-N 0.000 claims 1
• FULAUYGMXLNYKP-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[3-[2-(dimethylamino)-1-hydroxyethyl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=CC=C1)C(CN(C)C)O)C FULAUYGMXLNYKP-UHFFFAOYSA-N 0.000 claims 1
• SVTTWDDRNSJKCW-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[3-methoxy-4-(1-methylpiperidin-4-yl)anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)C1CCN(CC1)C)OC)C SVTTWDDRNSJKCW-UHFFFAOYSA-N 0.000 claims 1
• GIUZDPGYLBFNGJ-IRXDYDNUSA-N 6-(2,6-dichlorophenyl)-2-[3-methoxy-4-[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1[C@@H]2CN([C@H](C1)C2)C)OC)C GIUZDPGYLBFNGJ-IRXDYDNUSA-N 0.000 claims 1
• ZGOROSLDYMDTIU-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[4-(1,1-dioxo-1,4-thiazinan-4-yl)-3-(methylaminomethyl)anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1CCS(CC1)(=O)=O)CNC)C ZGOROSLDYMDTIU-UHFFFAOYSA-N 0.000 claims 1
• HKRAKIIDROVHCU-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[4-(1,1-dioxo-1,4-thiazinan-4-yl)anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1CCS(CC1)(=O)=O)C HKRAKIIDROVHCU-UHFFFAOYSA-N 0.000 claims 1
• AAKMZAPERHRRQH-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[4-(4,4-difluoropiperidin-1-yl)-3-[(dimethylamino)methyl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1CCC(CC1)(F)F)CN(C)C)C AAKMZAPERHRRQH-UHFFFAOYSA-N 0.000 claims 1
• OETXASZQVOJJIA-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[4-(dimethylamino)-3-(methylaminomethyl)anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N(C)C)CNC)C OETXASZQVOJJIA-UHFFFAOYSA-N 0.000 claims 1
• JOZMUYGWCBSIHQ-CALCHBBNSA-N 6-(2,6-dichlorophenyl)-2-[4-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-3-(methylaminomethyl)anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1C[C@@H](O[C@@H](C1)C)C)CNC)C JOZMUYGWCBSIHQ-CALCHBBNSA-N 0.000 claims 1
• VXEAJWZCVNCTBX-SFHVURJKSA-N 6-(2,6-dichlorophenyl)-2-[4-[(2S)-2-(hydroxymethyl)-4-methylpiperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1[C@@H](CN(CC1)C)CO)C VXEAJWZCVNCTBX-SFHVURJKSA-N 0.000 claims 1
• JPSBNNBBEUXTAR-QGZVFWFLSA-N 6-(2,6-dichlorophenyl)-2-[4-[(3R)-3,4-dimethylpiperazin-1-yl]-3-(methoxymethyl)anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1C[C@H](N(CC1)C)C)COC)C JPSBNNBBEUXTAR-QGZVFWFLSA-N 0.000 claims 1
• JGJVAYGKXJZQPK-WAIKUNEKSA-N 6-(2,6-dichlorophenyl)-2-[4-[(3R)-3-(methoxymethyl)piperazin-1-yl]-3-[(1R)-2,2,2-trifluoro-1-hydroxyethyl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1C[C@@H](NCC1)COC)[C@H](C(F)(F)F)O)C JGJVAYGKXJZQPK-WAIKUNEKSA-N 0.000 claims 1
• SMTWXSMNZNWQFB-SFHVURJKSA-N 6-(2,6-dichlorophenyl)-2-[4-[(3S)-3-(hydroxymethyl)-4-methylpiperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1C[C@H](N(CC1)C)CO)C SMTWXSMNZNWQFB-SFHVURJKSA-N 0.000 claims 1
• IAXXZTIEOKTWAU-CALCHBBNSA-N 6-(2,6-dichlorophenyl)-2-[4-[(3S,5R)-3,5-dimethylpiperazin-1-yl]-3-(hydroxymethyl)anilino]-8-ethyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1C[C@@H](N[C@@H](C1)C)C)CO)CC IAXXZTIEOKTWAU-CALCHBBNSA-N 0.000 claims 1
• WKVHJAMEXDRNPG-IYBDPMFKSA-N 6-(2,6-dichlorophenyl)-2-[4-[(3S,5R)-3,5-dimethylpiperazin-1-yl]-3-(hydroxymethyl)anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1C[C@@H](N[C@@H](C1)C)C)CO)C WKVHJAMEXDRNPG-IYBDPMFKSA-N 0.000 claims 1
• DRTNGDRJMJDMGG-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[4-[4-[2-(dimethylamino)acetyl]piperazin-1-yl]-3-(hydroxymethyl)anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1CCN(CC1)C(CN(C)C)=O)CO)C DRTNGDRJMJDMGG-UHFFFAOYSA-N 0.000 claims 1
• QCAHMNSTXUYWLG-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[4-fluoro-3-(methylaminomethyl)anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)F)CNC)C QCAHMNSTXUYWLG-UHFFFAOYSA-N 0.000 claims 1
• KGGPQAWGQMRSHY-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[4-methoxy-3-(methylaminomethyl)anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)OC)CNC)C KGGPQAWGQMRSHY-UHFFFAOYSA-N 0.000 claims 1
• WSLRACIXGJCAHP-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-[3-(methylaminomethyl)phenyl]-2-(4-morpholin-4-ylanilino)-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1CCOCC1)C1=CC(=CC=C1)CNC WSLRACIXGJCAHP-UHFFFAOYSA-N 0.000 claims 1
• FMPXJJDSJOHGPX-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-ethyl-2-(4-piperazin-1-ylanilino)-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1CCNCC1)CC FMPXJJDSJOHGPX-UHFFFAOYSA-N 0.000 claims 1
• PVPATQMZBYRKPR-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-(4-morpholin-4-ylanilino)-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1CCOCC1)C PVPATQMZBYRKPR-UHFFFAOYSA-N 0.000 claims 1
• CFSSLKDRPPPHQH-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[(11-methyl-11-azatricyclo[6.2.1.02,7]undeca-2(7),3,5-trien-4-yl)amino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound CN1C2CCC1C1=CC(NC3=NC=C4C(=O)N(CN(C)C4=N3)C3=C(Cl)C=CC=C3Cl)=CC=C21 CFSSLKDRPPPHQH-UHFFFAOYSA-N 0.000 claims 1
• VXFVONSGUSWYGN-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[3-(methylaminomethyl)-4-(1-methylpyrazol-4-yl)anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)C=1C=NN(C=1)C)CNC)C VXFVONSGUSWYGN-UHFFFAOYSA-N 0.000 claims 1
• YLZZOUYMBGFMQE-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[3-(methylaminomethyl)-4-pyridin-3-ylanilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)C=1C=NC=CC=1)CNC)C YLZZOUYMBGFMQE-UHFFFAOYSA-N 0.000 claims 1
• ZOGVRTNTUFJEFH-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[3-(methylaminomethyl)-4-pyridin-4-ylanilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)C1=CC=NC=C1)CNC)C ZOGVRTNTUFJEFH-UHFFFAOYSA-N 0.000 claims 1
• OECKMHDGPUVZFW-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[3-methyl-4-(1,2,3,6-tetrahydropyridin-4-yl)anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)C=1CCNCC=1)C)C OECKMHDGPUVZFW-UHFFFAOYSA-N 0.000 claims 1
• DYRFPPKNCVHRRI-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[3-methyl-4-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)C=1CCN(CC=1)C)C)C DYRFPPKNCVHRRI-UHFFFAOYSA-N 0.000 claims 1
• YPRQZRXZFZLNTA-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[4-(9-methyl-3-oxa-7,9-diazabicyclo[3.3.1]nonan-7-yl)anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1CC2COCC(C1)N2C)C YPRQZRXZFZLNTA-UHFFFAOYSA-N 0.000 claims 1
• GGPWOBTYIAYVDB-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-phenyl-2-(4-piperazin-1-ylanilino)-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1CCNCC1)C1=CC=CC=C1 GGPWOBTYIAYVDB-UHFFFAOYSA-N 0.000 claims 1
• IPDVNXZYSQXWMG-UHFFFAOYSA-N 6-(2-chloro-6-fluorophenyl)-2-[3-(hydroxymethyl)-4-(4-propan-2-ylpiperazin-1-yl)anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)F)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1CCN(CC1)C(C)C)CO)C IPDVNXZYSQXWMG-UHFFFAOYSA-N 0.000 claims 1
• KNFDRXWENVQALK-UHFFFAOYSA-N 6-(2-chloro-6-fluorophenyl)-2-[3-(hydroxymethyl)anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)F)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=CC=C1)CO)C KNFDRXWENVQALK-UHFFFAOYSA-N 0.000 claims 1
• LTHCLGLQFVDPSF-QGZVFWFLSA-N 6-(2-chloro-6-fluorophenyl)-2-[4-[(3R)-3-(methoxymethyl)piperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)F)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1C[C@@H](NCC1)COC)C LTHCLGLQFVDPSF-QGZVFWFLSA-N 0.000 claims 1
• SZLLSOCIXPGJLW-AEFFLSMTSA-N 6-(2-chlorophenyl)-2-[4-[(1S,4R)-2,5-diazabicyclo[2.2.1]heptan-2-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound CN1CN(C(=O)c2cnc(Nc3ccc(cc3)N3C[C@H]4C[C@H]3CN4)nc12)c1ccccc1Cl SZLLSOCIXPGJLW-AEFFLSMTSA-N 0.000 claims 1
• ACWWOMUHDKZSOX-CALCHBBNSA-N 6-(2-chlorophenyl)-2-[4-[(3S,5R)-3,5-dimethylpiperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C=CC=C1)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1C[C@@H](N[C@@H](C1)C)C)C ACWWOMUHDKZSOX-CALCHBBNSA-N 0.000 claims 1
• FRZOGTURUIMLDI-UHFFFAOYSA-N N-[[5-[[6-(2,6-dichlorophenyl)-8-methyl-5-oxo-7H-pyrimido[4,5-d]pyrimidin-2-yl]amino]-2-piperazin-1-ylphenyl]methyl]acetamide Chemical compound C(C)(=O)NCC1=C(C=CC(=C1)NC=1N=CC2=C(N(CN(C2=O)C2=C(C=CC=C2Cl)Cl)C)N1)N1CCNCC1 FRZOGTURUIMLDI-UHFFFAOYSA-N 0.000 claims 1
• 238000000034 method Methods 0.000 abstract description 492
• 108091000080 Phosphotransferase Proteins 0.000 abstract description 16
• 102000020233 phosphotransferase Human genes 0.000 abstract description 16
• 230000000694 effects Effects 0.000 abstract description 14
• 239000003112 inhibitor Substances 0.000 abstract description 11
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 448
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 369
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 328
• 238000005160 1H NMR spectroscopy Methods 0.000 description 245
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 210
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 206
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 201
• 239000007787 solid Substances 0.000 description 201
• 239000000203 mixture Substances 0.000 description 172
• 235000019439 ethyl acetate Nutrition 0.000 description 161
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 139
• 239000000243 solution Substances 0.000 description 129
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 103
• 239000011541 reaction mixture Substances 0.000 description 88
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 78
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 78
• ZNZIOXQCFILZLD-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-methylsulfanyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)SC)C ZNZIOXQCFILZLD-UHFFFAOYSA-N 0.000 description 76
• 230000002829 reductive effect Effects 0.000 description 75
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 62
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 60
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 58
• 239000002904 solvent Substances 0.000 description 58
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 58
• 239000000725 suspension Substances 0.000 description 57
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 54
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 54
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 52
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 50
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 45
• 239000012267 brine Substances 0.000 description 40
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 40
• 229910000027 potassium carbonate Inorganic materials 0.000 description 39
• 238000000746 purification Methods 0.000 description 38
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 36
• 238000004587 chromatography analysis Methods 0.000 description 33
• 239000012299 nitrogen atmosphere Substances 0.000 description 33
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 31
• 239000012074 organic phase Substances 0.000 description 31
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 29
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 28
• 238000001914 filtration Methods 0.000 description 28
• WFQDTOYDVUWQMS-UHFFFAOYSA-N 1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1 WFQDTOYDVUWQMS-UHFFFAOYSA-N 0.000 description 25
• 239000011521 glass Substances 0.000 description 25
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
• 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 24
• 239000012071 phase Substances 0.000 description 24
• 239000011734 sodium Substances 0.000 description 24
• 239000000377 silicon dioxide Substances 0.000 description 21
• 238000010828 elution Methods 0.000 description 20
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 19
• 150000001721 carbon Chemical group 0.000 description 19
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 19
• 239000007832 Na2SO4 Substances 0.000 description 18
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 18
• 229910052938 sodium sulfate Inorganic materials 0.000 description 18
• 235000011152 sodium sulphate Nutrition 0.000 description 18
• JEYPWZMNQANBEU-UHFFFAOYSA-N 6-(2-chlorophenyl)-8-methyl-2-methylsulfanyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C=CC=C1)N1CN(C2=NC(=NC=C2C1=O)SC)C JEYPWZMNQANBEU-UHFFFAOYSA-N 0.000 description 16
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
• 125000004452 carbocyclyl group Chemical group 0.000 description 16
• 238000001816 cooling Methods 0.000 description 16
• 239000010410 layer Substances 0.000 description 16
• 238000003818 flash chromatography Methods 0.000 description 15
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 14
• 150000001975 deuterium Chemical group 0.000 description 14
• 239000003921 oil Substances 0.000 description 14
• 235000019198 oils Nutrition 0.000 description 14
• 239000012044 organic layer Substances 0.000 description 14
• 238000010898 silica gel chromatography Methods 0.000 description 14
• 239000012279 sodium borohydride Substances 0.000 description 14
• 229910000033 sodium borohydride Inorganic materials 0.000 description 14
• 238000003756 stirring Methods 0.000 description 13
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 12
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
• VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 11
• 238000006243 chemical reaction Methods 0.000 description 11
• 239000000706 filtrate Substances 0.000 description 11
• AOOSQGSOXXIEJG-UHFFFAOYSA-N 6-(2-chloro-6-fluorophenyl)-8-methyl-2-methylsulfanyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)F)N1CN(C2=NC(=NC=C2C1=O)SC)C AOOSQGSOXXIEJG-UHFFFAOYSA-N 0.000 description 10
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 10
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
• 125000004429 atom Chemical group 0.000 description 10
• 210000004027 cell Anatomy 0.000 description 10
• 238000005984 hydrogenation reaction Methods 0.000 description 10
• 229920006395 saturated elastomer Polymers 0.000 description 10
• 235000017557 sodium bicarbonate Nutrition 0.000 description 10
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
• 239000006188 syrup Substances 0.000 description 10
• 235000020357 syrup Nutrition 0.000 description 10
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
• VVXFDFQEIRGULC-UHFFFAOYSA-N 2-fluoro-5-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=C(F)C(C=O)=C1 VVXFDFQEIRGULC-UHFFFAOYSA-N 0.000 description 9
• 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 9
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 9
• 229910000024 caesium carbonate Inorganic materials 0.000 description 9
• 239000002038 ethyl acetate fraction Substances 0.000 description 9
• 239000000284 extract Substances 0.000 description 9
• 235000019253 formic acid Nutrition 0.000 description 9
• 230000002401 inhibitory effect Effects 0.000 description 9
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
• 235000019341 magnesium sulphate Nutrition 0.000 description 9
• 125000003367 polycyclic group Chemical group 0.000 description 9
• 150000001204 N-oxides Chemical class 0.000 description 8
• 125000002252 acyl group Chemical group 0.000 description 8
• 239000008346 aqueous phase Substances 0.000 description 8
• 238000002474 experimental method Methods 0.000 description 8
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 8
• RFIOZSIHFNEKFF-UHFFFAOYSA-M piperazine-1-carboxylate Chemical compound [O-]C(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-M 0.000 description 8
• GBIDRUILIGWLJG-UHFFFAOYSA-N 6-(2-chloro-6-methylphenyl)-8-methyl-2-methylsulfanyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)C)N1CN(C2=NC(=NC=C2C1=O)SC)C GBIDRUILIGWLJG-UHFFFAOYSA-N 0.000 description 7
• QZBZTZUNXLZYKU-GFCCVEGCSA-N C[C@@H]1CN(CCN1C(=O)OC(C)(C)C)c1ccc(N)cc1 Chemical compound C[C@@H]1CN(CCN1C(=O)OC(C)(C)C)c1ccc(N)cc1 QZBZTZUNXLZYKU-GFCCVEGCSA-N 0.000 description 7
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
• 235000019270 ammonium chloride Nutrition 0.000 description 7
• 239000003795 chemical substances by application Substances 0.000 description 7
• FJBFPHVGVWTDIP-UHFFFAOYSA-N dibromomethane Chemical compound BrCBr FJBFPHVGVWTDIP-UHFFFAOYSA-N 0.000 description 7
• 239000002037 dichloromethane fraction Substances 0.000 description 7
• 150000002500 ions Chemical class 0.000 description 7
• 239000002244 precipitate Substances 0.000 description 7
• 239000012312 sodium hydride Substances 0.000 description 7
• 229910000104 sodium hydride Inorganic materials 0.000 description 7
• 238000002560 therapeutic procedure Methods 0.000 description 7
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
• 125000003368 amide group Chemical group 0.000 description 6
• 229910052801 chlorine Inorganic materials 0.000 description 6
• MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 6
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
• 238000005516 engineering process Methods 0.000 description 6
• 125000005842 heteroatom Chemical group 0.000 description 6
• 238000004128 high performance liquid chromatography Methods 0.000 description 6
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 6
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 6
• DATRVIMZZZVHMP-MRVPVSSYSA-N tert-butyl (2r)-2-methylpiperazine-1-carboxylate Chemical compound C[C@@H]1CNCCN1C(=O)OC(C)(C)C DATRVIMZZZVHMP-MRVPVSSYSA-N 0.000 description 6
• 238000011282 treatment Methods 0.000 description 6
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
• YVJMUXWGBCOIJK-UHFFFAOYSA-N N-(2,6-dichlorophenyl)-4-(methylamino)-2-methylsulfanylpyrimidine-5-carboxamide Chemical compound CNC1=C(C=NC(SC)=N1)C(=O)NC1=C(Cl)C=CC=C1Cl YVJMUXWGBCOIJK-UHFFFAOYSA-N 0.000 description 5
• 238000005481 NMR spectroscopy Methods 0.000 description 5
• 102000001253 Protein Kinase Human genes 0.000 description 5
• 125000001309 chloro group Chemical group Cl* 0.000 description 5
• 125000004122 cyclic group Chemical group 0.000 description 5
• 125000000392 cycloalkenyl group Chemical group 0.000 description 5
• 238000010438 heat treatment Methods 0.000 description 5
• 230000026731 phosphorylation Effects 0.000 description 5
• 238000006366 phosphorylation reaction Methods 0.000 description 5
• 239000000047 product Substances 0.000 description 5
• 108060006633 protein kinase Proteins 0.000 description 5
• 229910000029 sodium carbonate Inorganic materials 0.000 description 5
• 235000017550 sodium carbonate Nutrition 0.000 description 5
• RXFHRKPNLPBDGE-UHFFFAOYSA-N tert-butyl 4-(4-aminophenyl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=C(N)C=C1 RXFHRKPNLPBDGE-UHFFFAOYSA-N 0.000 description 5
• 125000006727 (C1-C6) alkenyl group Chemical group 0.000 description 4
• QXPZWBOUMKDDNX-UHFFFAOYSA-N 2-(4-acetylpiperazin-1-yl)-5-nitrobenzaldehyde Chemical compound C1CN(C(=O)C)CCN1C1=CC=C([N+]([O-])=O)C=C1C=O QXPZWBOUMKDDNX-UHFFFAOYSA-N 0.000 description 4
• WBFWJJYIJSLGFD-UHFFFAOYSA-N 4-chloro-n-(2,6-dichlorophenyl)-2-methylsulfanylpyrimidine-5-carboxamide Chemical compound ClC1=NC(SC)=NC=C1C(=O)NC1=C(Cl)C=CC=C1Cl WBFWJJYIJSLGFD-UHFFFAOYSA-N 0.000 description 4
• AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
• 108010078814 Tumor Suppressor Protein p53 Proteins 0.000 description 4
• 125000004390 alkyl sulfonyl group Chemical group 0.000 description 4
• 125000000304 alkynyl group Chemical group 0.000 description 4
• 229910021529 ammonia Inorganic materials 0.000 description 4
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
• 230000022131 cell cycle Effects 0.000 description 4
• NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 4
• 201000010099 disease Diseases 0.000 description 4
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
• 238000000132 electrospray ionisation Methods 0.000 description 4
• 125000004366 heterocycloalkenyl group Chemical group 0.000 description 4
• 238000001727 in vivo Methods 0.000 description 4
• 239000002480 mineral oil Substances 0.000 description 4
• 235000010446 mineral oil Nutrition 0.000 description 4
• 125000002950 monocyclic group Chemical group 0.000 description 4
• 230000035772 mutation Effects 0.000 description 4
• 238000001959 radiotherapy Methods 0.000 description 4
• MHOYZHJILBQLFT-OLZOCXBDSA-N tert-butyl (2S,5R)-4-(4-aminophenyl)-2,5-dimethylpiperazine-1-carboxylate Chemical compound NC1=CC=C(C=C1)N1C[C@@H](N(C[C@H]1C)C(=O)OC(C)(C)C)C MHOYZHJILBQLFT-OLZOCXBDSA-N 0.000 description 4
• 239000003643 water by type Substances 0.000 description 4
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 3
• RUBQQRMAWLSCCJ-UHFFFAOYSA-N 1,2-difluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C(F)=C1 RUBQQRMAWLSCCJ-UHFFFAOYSA-N 0.000 description 3
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
• XUCYJGMIICONES-UHFFFAOYSA-N 1-fluoro-2-methyl-4-nitrobenzene Chemical compound CC1=CC([N+]([O-])=O)=CC=C1F XUCYJGMIICONES-UHFFFAOYSA-N 0.000 description 3
• JDMFXJULNGEPOI-UHFFFAOYSA-N 2,6-dichloroaniline Chemical compound NC1=C(Cl)C=CC=C1Cl JDMFXJULNGEPOI-UHFFFAOYSA-N 0.000 description 3
• YULKSKDPASSZNR-UHFFFAOYSA-N 4-(methylamino)-2-methylsulfanylpyrimidine-5-carboxylic acid Chemical compound CNC1=NC(SC)=NC=C1C(O)=O YULKSKDPASSZNR-UHFFFAOYSA-N 0.000 description 3
• FPBFBURPCHKEKH-AOOOYVTPSA-N 4-[(3r,5s)-3,5-dimethylpiperazin-1-yl]aniline Chemical compound C1[C@@H](C)N[C@@H](C)CN1C1=CC=C(N)C=C1 FPBFBURPCHKEKH-AOOOYVTPSA-N 0.000 description 3
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 3
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• 101150012716 CDK1 gene Proteins 0.000 description 3
• 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 3
• 230000005778 DNA damage Effects 0.000 description 3
• 231100000277 DNA damage Toxicity 0.000 description 3
• 101100059559 Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) nimX gene Proteins 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 3
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
• 206010039491 Sarcoma Diseases 0.000 description 3
• 101100273808 Xenopus laevis cdk1-b gene Proteins 0.000 description 3
• RPZMEFKGZKMAPD-UHFFFAOYSA-N [5-amino-2-(4-ethylpiperazin-1-yl)phenyl]methanol Chemical compound C1CN(CC)CCN1C1=CC=C(N)C=C1CO RPZMEFKGZKMAPD-UHFFFAOYSA-N 0.000 description 3
• MYAYHIGUYSQMPX-UHFFFAOYSA-N [5-amino-2-(4-propan-2-ylpiperazin-1-yl)phenyl]methanol Chemical compound NC=1C=CC(=C(C1)CO)N1CCN(CC1)C(C)C MYAYHIGUYSQMPX-UHFFFAOYSA-N 0.000 description 3
• 239000002253 acid Substances 0.000 description 3
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
• 125000003710 aryl alkyl group Chemical group 0.000 description 3
• 239000000460 chlorine Substances 0.000 description 3
• 239000013078 crystal Substances 0.000 description 3
• 230000006378 damage Effects 0.000 description 3
• NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 3
• 229910052731 fluorine Inorganic materials 0.000 description 3
• 125000001153 fluoro group Chemical group F* 0.000 description 3
• 239000006260 foam Substances 0.000 description 3
• 125000005298 iminyl group Chemical group 0.000 description 3
• 230000005764 inhibitory process Effects 0.000 description 3
• 125000001786 isothiazolyl group Chemical group 0.000 description 3
• 125000000842 isoxazolyl group Chemical group 0.000 description 3
• 230000003902 lesion Effects 0.000 description 3
• 230000014759 maintenance of location Effects 0.000 description 3
• 201000001441 melanoma Diseases 0.000 description 3
• 230000011278 mitosis Effects 0.000 description 3
• KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 3
• FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 3
• 229940002612 prodrug Drugs 0.000 description 3
• 239000000651 prodrug Substances 0.000 description 3
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 3
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 3
• 238000010992 reflux Methods 0.000 description 3
• 239000000523 sample Substances 0.000 description 3
• 150000003384 small molecules Chemical class 0.000 description 3
• 239000007858 starting material Substances 0.000 description 3
• 239000000126 substance Substances 0.000 description 3
• SEXLALOUSMFTCE-KBPBESRZSA-N tert-butyl (1S,4S)-5-(4-amino-2-methylphenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound NC1=CC(=C(C=C1)N1[C@@H]2CN([C@H](C1)C2)C(=O)OC(C)(C)C)C SEXLALOUSMFTCE-KBPBESRZSA-N 0.000 description 3
• LPLCFNQVYQRJML-GFCCVEGCSA-N tert-butyl (2R)-4-(2-formyl-4-nitrophenyl)-2-methylpiperazine-1-carboxylate Chemical compound C(=O)C1=C(C=CC(=C1)[N+](=O)[O-])N1C[C@H](N(CC1)C(=O)OC(C)(C)C)C LPLCFNQVYQRJML-GFCCVEGCSA-N 0.000 description 3
• QPWCNTNIGOXGAX-CYBMUJFWSA-N tert-butyl (2R)-4-[4-amino-2-(methoxymethyl)phenyl]-2-methylpiperazine-1-carboxylate Chemical compound NC1=CC(=C(C=C1)N1C[C@H](N(CC1)C(=O)OC(C)(C)C)C)COC QPWCNTNIGOXGAX-CYBMUJFWSA-N 0.000 description 3
• AAJUFMWASPADJF-AWEZNQCLSA-N tert-butyl (3S)-3-(hydroxymethyl)-4-(4-nitrophenyl)piperazine-1-carboxylate Chemical compound OC[C@@H]1CN(CCN1C1=CC=C(C=C1)[N+](=O)[O-])C(=O)OC(C)(C)C AAJUFMWASPADJF-AWEZNQCLSA-N 0.000 description 3
• ZLOWQQWAHOEBKP-UHFFFAOYSA-N tert-butyl 2,2-dimethyl-4-(4-nitrophenyl)piperazine-1-carboxylate Chemical compound C1C(C)(C)N(C(=O)OC(C)(C)C)CCN1C1=CC=C([N+]([O-])=O)C=C1 ZLOWQQWAHOEBKP-UHFFFAOYSA-N 0.000 description 3
• IQNHWLJILCSSLY-UHFFFAOYSA-N tert-butyl 3-[4-amino-2-(hydroxymethyl)phenyl]-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound NC1=CC(=C(C=C1)N1CC2CCC(C1)N2C(=O)OC(C)(C)C)CO IQNHWLJILCSSLY-UHFFFAOYSA-N 0.000 description 3
• QSSVQUXXRYNJIZ-UHFFFAOYSA-N tert-butyl 4-(4-amino-2-methylphenyl)piperazine-1-carboxylate Chemical compound CC1=CC(N)=CC=C1N1CCN(C(=O)OC(C)(C)C)CC1 QSSVQUXXRYNJIZ-UHFFFAOYSA-N 0.000 description 3
• QUKABSSPBMVPRN-UHFFFAOYSA-N tert-butyl 4-(4-aminophenyl)-2,2-dimethylpiperazine-1-carboxylate Chemical compound C1C(C)(C)N(C(=O)OC(C)(C)C)CCN1C1=CC=C(N)C=C1 QUKABSSPBMVPRN-UHFFFAOYSA-N 0.000 description 3
• VQGFKSZCPHGFJQ-UHFFFAOYSA-N tert-butyl 4-[2-(hydroxymethyl)-4-nitrophenyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=C([N+]([O-])=O)C=C1CO VQGFKSZCPHGFJQ-UHFFFAOYSA-N 0.000 description 3
• MSHOAMKWZLYPLO-UHFFFAOYSA-N tert-butyl 4-[4-amino-2-(methoxymethyl)phenyl]piperazine-1-carboxylate Chemical compound COCC1=C(C=CC(N)=C1)N1CCN(CC1)C(=O)OC(C)(C)C MSHOAMKWZLYPLO-UHFFFAOYSA-N 0.000 description 3
• UBLZWKCJZSDBGQ-AOOOYVTPSA-N (3r,5s)-3,5-dimethyl-1-(4-nitrophenyl)piperazine Chemical compound C1[C@@H](C)N[C@@H](C)CN1C1=CC=C([N+]([O-])=O)C=C1 UBLZWKCJZSDBGQ-AOOOYVTPSA-N 0.000 description 2
• VUCXPUVUVWCVDL-UHFFFAOYSA-N (5-amino-2-morpholin-4-ylphenyl)methanol Chemical compound OCC1=CC(N)=CC=C1N1CCOCC1 VUCXPUVUVWCVDL-UHFFFAOYSA-N 0.000 description 2
• DLOPNHLQMXRXND-UHFFFAOYSA-N (5-amino-2-piperidin-1-ylphenyl)methanol Chemical compound NC=1C=CC(=C(C1)CO)N1CCCCC1 DLOPNHLQMXRXND-UHFFFAOYSA-N 0.000 description 2
• VKAPZEAZRQDVIK-UHFFFAOYSA-N (5-nitro-2-pyrrolidin-1-ylphenyl)methanol Chemical compound OCC1=CC([N+]([O-])=O)=CC=C1N1CCCC1 VKAPZEAZRQDVIK-UHFFFAOYSA-N 0.000 description 2
• KHJBPXHXSDVQNW-UHFFFAOYSA-N 1,2,2-trimethyl-4-(4-nitrophenyl)piperazine Chemical compound C1C(C)(C)N(C)CCN1C1=CC=C([N+]([O-])=O)C=C1 KHJBPXHXSDVQNW-UHFFFAOYSA-N 0.000 description 2
• 125000004529 1,2,3-triazinyl group Chemical group N1=NN=C(C=C1)* 0.000 description 2
• 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 2
• 125000003363 1,3,5-triazinyl group Chemical group N1=C(N=CN=C1)* 0.000 description 2
• DVDGFEMAHCRKON-UHFFFAOYSA-N 1-(2-methoxyethyl)-4-(4-nitrophenyl)piperazine Chemical compound C1CN(CCOC)CCN1C1=CC=C([N+]([O-])=O)C=C1 DVDGFEMAHCRKON-UHFFFAOYSA-N 0.000 description 2
• XZWFLGWJRYVEQS-UHFFFAOYSA-N 1-(4-nitrophenyl)-3-(trifluoromethyl)piperazine Chemical compound [N+](=O)([O-])C1=CC=C(C=C1)N1CC(NCC1)C(F)(F)F XZWFLGWJRYVEQS-UHFFFAOYSA-N 0.000 description 2
• FVVWTOOFOVQVLX-UHFFFAOYSA-N 1-[4-[2-(methylaminomethyl)-4-nitrophenyl]piperazin-1-yl]ethanone Chemical compound CNCC1=C(C=CC(=C1)[N+](=O)[O-])N1CCN(CC1)C(C)=O FVVWTOOFOVQVLX-UHFFFAOYSA-N 0.000 description 2
• BFLLLVNDKSDPCX-UHFFFAOYSA-N 1-[4-[2-[(dimethylamino)methyl]-4-nitrophenyl]piperazin-1-yl]ethanone Chemical compound CN(C)CC1=C(C=CC(=C1)[N+](=O)[O-])N1CCN(CC1)C(C)=O BFLLLVNDKSDPCX-UHFFFAOYSA-N 0.000 description 2
• GOMXTQSKSQHHIB-UHFFFAOYSA-N 1-[4-[4-amino-2-(pyrrolidin-1-ylmethyl)phenyl]piperazin-1-yl]ethanone Chemical compound NC1=CC(=C(C=C1)N1CCN(CC1)C(C)=O)CN1CCCC1 GOMXTQSKSQHHIB-UHFFFAOYSA-N 0.000 description 2
• FTANELUNKRTQBI-UHFFFAOYSA-N 1-[4-[4-nitro-2-(pyrrolidin-1-ylmethyl)phenyl]piperazin-1-yl]ethanone Chemical compound [N+](=O)([O-])C1=CC(=C(C=C1)N1CCN(CC1)C(C)=O)CN1CCCC1 FTANELUNKRTQBI-UHFFFAOYSA-N 0.000 description 2
• JFFPRVLUZCLWSF-UHFFFAOYSA-N 1-bromo-2-(difluoromethoxy)-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Br)C(OC(F)F)=C1 JFFPRVLUZCLWSF-UHFFFAOYSA-N 0.000 description 2
• WYHRUYMSJSNTOH-UHFFFAOYSA-N 1-cyclopropyl-4-(4-nitrophenyl)piperazine Chemical compound C1=CC([N+](=O)[O-])=CC=C1N1CCN(C2CC2)CC1 WYHRUYMSJSNTOH-UHFFFAOYSA-N 0.000 description 2
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 2
• NRKYWOKHZRQRJR-UHFFFAOYSA-N 2,2,2-trifluoroacetamide Chemical compound NC(=O)C(F)(F)F NRKYWOKHZRQRJR-UHFFFAOYSA-N 0.000 description 2
• ZNZIOXQCFILZLD-RJSZUWSASA-N 2,2-dideuterio-3-(2,6-dichlorophenyl)-1-methyl-7-methylsulfanylpyrimido[4,5-d]pyrimidin-4-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1C(N(C2=NC(=NC=C2C1=O)SC)C)([2H])[2H] ZNZIOXQCFILZLD-RJSZUWSASA-N 0.000 description 2
• ZEHHYRIHOWXOTH-UHFFFAOYSA-N 2-(4-ethylpiperazin-1-yl)-5-nitrobenzaldehyde Chemical compound C1CN(CC)CCN1C1=CC=C([N+]([O-])=O)C=C1C=O ZEHHYRIHOWXOTH-UHFFFAOYSA-N 0.000 description 2
• ZGUMAGSCPSAQBV-ZDUSSCGKSA-N 2-[(9aS)-3,4,6,7,9,9a-hexahydro-1H-pyrazino[2,1-c][1,4]oxazin-8-yl]-5-nitrobenzaldehyde Chemical compound C1OCCN2[C@H]1CN(CC2)C2=C(C=O)C=C(C=C2)[N+](=O)[O-] ZGUMAGSCPSAQBV-ZDUSSCGKSA-N 0.000 description 2
• CLIQDJPUGBOASZ-UHFFFAOYSA-N 2-[4-(3,8-diazabicyclo[3.2.1]octan-3-yl)-3-(hydroxymethyl)anilino]-6-(2,6-dichlorophenyl)-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound C12CN(CC(CC1)N2)C1=C(C=C(C=C1)NC1=NC=C2C(=N1)N(CN(C2=O)C1=C(C=CC=C1Cl)Cl)C)CO CLIQDJPUGBOASZ-UHFFFAOYSA-N 0.000 description 2
• HCDBHFCQLBZAAZ-UHFFFAOYSA-N 2-[4-(4-aminophenyl)piperazin-1-yl]ethanol Chemical compound C1=CC(N)=CC=C1N1CCN(CCO)CC1 HCDBHFCQLBZAAZ-UHFFFAOYSA-N 0.000 description 2
• WVNPWSRYQDRSIS-UHFFFAOYSA-N 2-[4-(4-nitrophenyl)piperazin-1-yl]ethanol Chemical compound C1CN(CCO)CCN1C1=CC=C([N+]([O-])=O)C=C1 WVNPWSRYQDRSIS-UHFFFAOYSA-N 0.000 description 2
• VFVHWCKUHAEDMY-UHFFFAOYSA-N 2-chloro-5-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=C(Cl)C(C=O)=C1 VFVHWCKUHAEDMY-UHFFFAOYSA-N 0.000 description 2
• PCGDWIWUQDHQLK-UHFFFAOYSA-N 2-morpholin-4-yl-5-nitrobenzaldehyde Chemical compound O=CC1=CC([N+](=O)[O-])=CC=C1N1CCOCC1 PCGDWIWUQDHQLK-UHFFFAOYSA-N 0.000 description 2
• PUXMXWUZKNBENK-UHFFFAOYSA-N 4-(3,3,4-trimethylpiperazin-1-yl)aniline Chemical compound C1C(C)(C)N(C)CCN1C1=CC=C(N)C=C1 PUXMXWUZKNBENK-UHFFFAOYSA-N 0.000 description 2
• BNJJOUMQLDDFMK-UHFFFAOYSA-N 4-(4-cyclopropylpiperazin-1-yl)aniline Chemical compound C1=CC(N)=CC=C1N1CCN(C2CC2)CC1 BNJJOUMQLDDFMK-UHFFFAOYSA-N 0.000 description 2
• IIOZABPJXJSPBJ-UHFFFAOYSA-N 4-(cyclopropylamino)-N-(2,6-dichlorophenyl)-2-methylsulfanylpyrimidine-5-carboxamide Chemical compound CSC1=NC(NC2CC2)=C(C=N1)C(=O)NC1=C(Cl)C=CC=C1Cl IIOZABPJXJSPBJ-UHFFFAOYSA-N 0.000 description 2
• LZYIXSDJJBZCEM-UHFFFAOYSA-N 4-[4-(2-methoxyethyl)piperazin-1-yl]aniline Chemical compound C1CN(CCOC)CCN1C1=CC=C(N)C=C1 LZYIXSDJJBZCEM-UHFFFAOYSA-N 0.000 description 2
• NMFCRGDGVPCDHH-UHFFFAOYSA-N 4-chloro-2-methylsulfanylpyrimidine-5-carbonyl chloride Chemical compound CSC1=NC=C(C(Cl)=O)C(Cl)=N1 NMFCRGDGVPCDHH-UHFFFAOYSA-N 0.000 description 2
• QGUVZIRJWVECOI-UHFFFAOYSA-N 5-nitro-2-(4-propan-2-ylpiperazin-1-yl)benzaldehyde Chemical compound C1CN(C(C)C)CCN1C1=CC=C([N+]([O-])=O)C=C1C=O QGUVZIRJWVECOI-UHFFFAOYSA-N 0.000 description 2
• WPONLEWKUHGAEI-UHFFFAOYSA-N 5-nitro-2-piperidin-1-ylbenzaldehyde Chemical compound O=CC1=CC([N+](=O)[O-])=CC=C1N1CCCCC1 WPONLEWKUHGAEI-UHFFFAOYSA-N 0.000 description 2
• JFQMJKUZCQPCHM-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-7,8-dimethyl-2-methylsulfanyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1C(N(C2=NC(=NC=C2C1=O)SC)C)C JFQMJKUZCQPCHM-UHFFFAOYSA-N 0.000 description 2
• UYLDIMQJAQZPEN-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-(1-methylpyrazol-3-yl)-2-methylsulfanyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)SC)C1=NN(C=C1)C UYLDIMQJAQZPEN-UHFFFAOYSA-N 0.000 description 2
• SMNRGINXNGKONU-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-[(4-methoxyphenyl)methyl]-2-methylsulfanyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)SC)CC1=CC=C(C=C1)OC SMNRGINXNGKONU-UHFFFAOYSA-N 0.000 description 2
• BJQGPQKCIHJMBZ-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-(4-methylsulfinylanilino)-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)S(=O)C)C BJQGPQKCIHJMBZ-UHFFFAOYSA-N 0.000 description 2
• KLMLSIGZOXMYSQ-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[3-(piperidin-4-ylamino)anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=CC=C1)NC1CCNCC1)C KLMLSIGZOXMYSQ-UHFFFAOYSA-N 0.000 description 2
• REEVPCDMEOSDTB-OAHLLOKOSA-N 6-(2-chlorophenyl)-2-[3-fluoro-4-[(3R)-3-methylpiperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C=CC=C1)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1C[C@H](NCC1)C)F)C REEVPCDMEOSDTB-OAHLLOKOSA-N 0.000 description 2
• BSOANRVSHSJEMT-UHFFFAOYSA-N 6-(2-chlorophenyl)-2-[4-(3,8-diazabicyclo[3.2.1]octan-3-yl)-3-(hydroxymethyl)anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound C12CN(CC(CC1)N2)C1=C(C=C(C=C1)NC1=NC=C2C(=N1)N(CN(C2=O)C1=C(C=CC=C1)Cl)C)CO BSOANRVSHSJEMT-UHFFFAOYSA-N 0.000 description 2
• NNAIPZWMYLGKDZ-UHFFFAOYSA-N 8-cyclopropyl-6-(2,6-dichlorophenyl)-2-methylsulfanyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound C1(CC1)N1CN(C(C=2C1=NC(=NC=2)SC)=O)C1=C(C=CC=C1Cl)Cl NNAIPZWMYLGKDZ-UHFFFAOYSA-N 0.000 description 2
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
• 101150050673 CHK1 gene Proteins 0.000 description 2
• NWCNWZHURXELRF-UHFFFAOYSA-N COC1=CC=C(CNC2=NC(=NC=C2C(=O)O)SC)C=C1 Chemical compound COC1=CC=C(CNC2=NC(=NC=C2C(=O)O)SC)C=C1 NWCNWZHURXELRF-UHFFFAOYSA-N 0.000 description 2
• 101100220616 Caenorhabditis elegans chk-2 gene Proteins 0.000 description 2
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
• UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 2
• 239000012623 DNA damaging agent Substances 0.000 description 2
• 230000033616 DNA repair Effects 0.000 description 2
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 239000007821 HATU Substances 0.000 description 2
• 101001047681 Homo sapiens Tyrosine-protein kinase Lck Proteins 0.000 description 2
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
• 241000124008 Mammalia Species 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• FFDGPVCHZBVARC-UHFFFAOYSA-N N,N-dimethylglycine Chemical compound CN(C)CC(O)=O FFDGPVCHZBVARC-UHFFFAOYSA-N 0.000 description 2
• SUARSRTWHXIEQZ-UHFFFAOYSA-N N-(2,6-dichlorophenyl)-4-[(4-methoxyphenyl)methylamino]-2-methylsulfanylpyrimidine-5-carboxamide Chemical compound COC1=CC=C(CNC2=C(C=NC(SC)=N2)C(=O)NC2=C(Cl)C=CC=C2Cl)C=C1 SUARSRTWHXIEQZ-UHFFFAOYSA-N 0.000 description 2
• KCOYSRMCXVMIAC-UHFFFAOYSA-N N-(2-chloro-6-fluorophenyl)-4-(methylamino)-2-methylsulfanylpyrimidine-5-carboxamide Chemical compound CNC1=C(C=NC(SC)=N1)C(=O)NC1=C(Cl)C=CC=C1F KCOYSRMCXVMIAC-UHFFFAOYSA-N 0.000 description 2
• NPMLCZXFQQYCAP-UHFFFAOYSA-N N-(2-chloro-6-methylphenyl)-4-(methylamino)-2-methylsulfanylpyrimidine-5-carboxamide Chemical compound CNC1=C(C=NC(SC)=N1)C(=O)NC1=C(Cl)C=CC=C1C NPMLCZXFQQYCAP-UHFFFAOYSA-N 0.000 description 2
• BDALCHYUITZZGJ-UHFFFAOYSA-N N-(2-chlorophenyl)-4-(methylamino)-2-methylsulfanylpyrimidine-5-carboxamide Chemical compound CNC1=C(C=NC(SC)=N1)C(=O)NC1=C(Cl)C=CC=C1 BDALCHYUITZZGJ-UHFFFAOYSA-N 0.000 description 2
• VQWVKDTXWLMNNR-UHFFFAOYSA-N N-methyl-1-(2-morpholin-4-yl-5-nitrophenyl)methanamine Chemical compound CNCc1cc(ccc1N1CCOCC1)[N+]([O-])=O VQWVKDTXWLMNNR-UHFFFAOYSA-N 0.000 description 2
• MJUJCLKGVZGQMR-UHFFFAOYSA-N N-methyl-1-(5-nitro-2-piperidin-1-ylphenyl)methanamine Chemical compound CNCC1=C(C=CC(=C1)[N+](=O)[O-])N1CCCCC1 MJUJCLKGVZGQMR-UHFFFAOYSA-N 0.000 description 2
• TVCOPAYKEHATPK-UHFFFAOYSA-N N-methyl-1-(5-nitro-2-pyrrolidin-1-ylphenyl)methanamine Chemical compound CNCC1=C(C=CC(=C1)[N+](=O)[O-])N1CCCC1 TVCOPAYKEHATPK-UHFFFAOYSA-N 0.000 description 2
• MAAANNOXLUWFFH-UHFFFAOYSA-N NC=1C=CC(=C(CN(C(OC(C)(C)C)=O)C)C1)N1CCOCC1 Chemical compound NC=1C=CC(=C(CN(C(OC(C)(C)C)=O)C)C1)N1CCOCC1 MAAANNOXLUWFFH-UHFFFAOYSA-N 0.000 description 2
• LAWPTUQHDKLJML-UHFFFAOYSA-N NC=1C=CC(=C(CN(C(OC(C)(C)C)=O)C)C=1)N1CCCCC1 Chemical compound NC=1C=CC(=C(CN(C(OC(C)(C)C)=O)C)C=1)N1CCCCC1 LAWPTUQHDKLJML-UHFFFAOYSA-N 0.000 description 2
• 235000019502 Orange oil Nutrition 0.000 description 2
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
• 102000001332 SRC Human genes 0.000 description 2
• 108060006706 SRC Proteins 0.000 description 2
• NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 2
• 102100024036 Tyrosine-protein kinase Lck Human genes 0.000 description 2
• 208000027418 Wounds and injury Diseases 0.000 description 2
• GDDIUVGMPVNNNP-UHFFFAOYSA-N [2-(4-ethylpiperazin-1-yl)-5-nitrophenyl]methanol Chemical compound C1CN(CC)CCN1C1=CC=C([N+]([O-])=O)C=C1CO GDDIUVGMPVNNNP-UHFFFAOYSA-N 0.000 description 2
• BSZMNBCBDNQQEW-ZDUSSCGKSA-N [2-[(9aS)-3,4,6,7,9,9a-hexahydro-1H-pyrazino[2,1-c][1,4]oxazin-8-yl]-5-aminophenyl]methanol Chemical compound NC1=CC(CO)=C(C=C1)N1CCN2CCOC[C@@H]2C1 BSZMNBCBDNQQEW-ZDUSSCGKSA-N 0.000 description 2
• YEHJWVBQCOKPSA-ZDUSSCGKSA-N [2-[(9aS)-3,4,6,7,9,9a-hexahydro-1H-pyrazino[2,1-c][1,4]oxazin-8-yl]-5-nitrophenyl]methanol Chemical compound C1OCCN2[C@H]1CN(CC2)C2=C(C=C(C=C2)[N+](=O)[O-])CO YEHJWVBQCOKPSA-ZDUSSCGKSA-N 0.000 description 2
• AJCCOHSHWMPQMW-UHFFFAOYSA-N [5-nitro-2-(4-propan-2-ylpiperazin-1-yl)phenyl]methanol Chemical compound C1CN(C(C)C)CCN1C1=CC=C([N+]([O-])=O)C=C1CO AJCCOHSHWMPQMW-UHFFFAOYSA-N 0.000 description 2
• ZBIKORITPGTTGI-UHFFFAOYSA-N [acetyloxy(phenyl)-$l^{3}-iodanyl] acetate Chemical compound CC(=O)OI(OC(C)=O)C1=CC=CC=C1 ZBIKORITPGTTGI-UHFFFAOYSA-N 0.000 description 2
• 230000001919 adrenal effect Effects 0.000 description 2
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
• 239000002168 alkylating agent Substances 0.000 description 2
• 229940100198 alkylating agent Drugs 0.000 description 2
• 239000000908 ammonium hydroxide Substances 0.000 description 2
• 230000000340 anti-metabolite Effects 0.000 description 2
• 229940100197 antimetabolite Drugs 0.000 description 2
• 239000002256 antimetabolite Substances 0.000 description 2
• 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 description 2
• 239000012298 atmosphere Substances 0.000 description 2
• VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 2
• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
• 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 2
• 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 2
• 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 description 2
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 2
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
• 125000002618 bicyclic heterocycle group Chemical group 0.000 description 2
• 210000004369 blood Anatomy 0.000 description 2
• 239000008280 blood Substances 0.000 description 2
• 210000000481 breast Anatomy 0.000 description 2
• VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 2
• 229960004562 carboplatin Drugs 0.000 description 2
• 101150113535 chek1 gene Proteins 0.000 description 2
• 229920001429 chelating resin Polymers 0.000 description 2
• 238000000451 chemical ionisation Methods 0.000 description 2
• 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 2
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 2
• 229960004316 cisplatin Drugs 0.000 description 2
• 229910052681 coesite Inorganic materials 0.000 description 2
• 230000000875 corresponding effect Effects 0.000 description 2
• 229910052906 cristobalite Inorganic materials 0.000 description 2
• 239000012043 crude product Substances 0.000 description 2
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
• 229960000684 cytarabine Drugs 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• 239000003534 dna topoisomerase inhibitor Substances 0.000 description 2
• 229960004679 doxorubicin Drugs 0.000 description 2
• 239000011737 fluorine Substances 0.000 description 2
• 229960002949 fluorouracil Drugs 0.000 description 2
• 125000002541 furyl group Chemical group 0.000 description 2
• SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 2
• 229960005277 gemcitabine Drugs 0.000 description 2
• 239000008103 glucose Substances 0.000 description 2
• 229910052739 hydrogen Inorganic materials 0.000 description 2
• 239000001257 hydrogen Substances 0.000 description 2
• 230000002779 inactivation Effects 0.000 description 2
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 2
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 2
• 125000001041 indolyl group Chemical group 0.000 description 2
• 208000014674 injury Diseases 0.000 description 2
• NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical compound CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 description 2
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 2
• 238000004811 liquid chromatography Methods 0.000 description 2
• 210000001853 liver microsome Anatomy 0.000 description 2
• 238000004949 mass spectrometry Methods 0.000 description 2
• GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 2
• 210000001589 microsome Anatomy 0.000 description 2
• 239000012452 mother liquor Substances 0.000 description 2
• 125000001624 naphthyl group Chemical group 0.000 description 2
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 2
• 210000001989 nasopharynx Anatomy 0.000 description 2
• GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
• 239000010502 orange oil Substances 0.000 description 2
• 150000007524 organic acids Chemical group 0.000 description 2
• 125000001715 oxadiazolyl group Chemical group 0.000 description 2
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 2
• 125000004193 piperazinyl group Chemical group 0.000 description 2
• DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 2
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
• VLYFRFHWUBBLRR-UHFFFAOYSA-L potassium;sodium;carbonate Chemical compound [Na+].[K+].[O-]C([O-])=O VLYFRFHWUBBLRR-UHFFFAOYSA-L 0.000 description 2
• 238000002953 preparative HPLC Methods 0.000 description 2
• 230000008569 process Effects 0.000 description 2
• 239000003909 protein kinase inhibitor Substances 0.000 description 2
• 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 2
• 125000002098 pyridazinyl group Chemical group 0.000 description 2
• 125000000714 pyrimidinyl group Chemical group 0.000 description 2
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 2
• 230000005855 radiation Effects 0.000 description 2
• VUPQHSHTKBZVML-UHFFFAOYSA-J rhodium(3+);tetraacetate Chemical compound [Rh+3].[Rh+3].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O VUPQHSHTKBZVML-UHFFFAOYSA-J 0.000 description 2
• 238000013341 scale-up Methods 0.000 description 2
• 239000012056 semi-solid material Substances 0.000 description 2
• 230000035945 sensitivity Effects 0.000 description 2
• 235000012239 silicon dioxide Nutrition 0.000 description 2
• 229910052682 stishovite Inorganic materials 0.000 description 2
• BGEBIECWPPJYKF-ZIAGYGMSSA-N tert-butyl (1R,4R)-5-(2-methyl-4-nitrophenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound CC1=C(C=CC(=C1)[N+](=O)[O-])N1[C@H]2CN([C@@H](C1)C2)C(=O)OC(C)(C)C BGEBIECWPPJYKF-ZIAGYGMSSA-N 0.000 description 2
• XRMVYRNFXRZAEL-STQMWFEESA-N tert-butyl (1S,4S)-5-(4-amino-2-methoxyphenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound NC1=CC(=C(C=C1)N1[C@@H]2CN([C@H](C1)C2)C(=O)OC(C)(C)C)OC XRMVYRNFXRZAEL-STQMWFEESA-N 0.000 description 2
• SRRQHCQKLIAFPQ-CQSZACIVSA-N tert-butyl (2R)-2-(hydroxymethyl)-4-(4-nitrophenyl)piperazine-1-carboxylate Chemical compound OC[C@@H]1N(CCN(C1)C1=CC=C(C=C1)[N+](=O)[O-])C(=O)OC(C)(C)C SRRQHCQKLIAFPQ-CQSZACIVSA-N 0.000 description 2
• VZOFUUPIDSMRTF-CYBMUJFWSA-N tert-butyl (2R)-4-(2-ethoxycarbonyl-4-nitrophenyl)-2-methylpiperazine-1-carboxylate Chemical compound C(C)OC(=O)C1=C(C=CC(=C1)[N+](=O)[O-])N1C[C@H](N(CC1)C(=O)OC(C)(C)C)C VZOFUUPIDSMRTF-CYBMUJFWSA-N 0.000 description 2
• FWWMYBNNAMKWBL-LLVKDONJSA-N tert-butyl (2R)-4-(2-fluoro-4-nitrophenyl)-2-methylpiperazine-1-carboxylate Chemical compound FC1=C(C=CC(=C1)[N+](=O)[O-])N1C[C@H](N(CC1)C(=O)OC(C)(C)C)C FWWMYBNNAMKWBL-LLVKDONJSA-N 0.000 description 2
• SKUOYTXUYXQHPC-OAHLLOKOSA-N tert-butyl (2R)-4-(2-formyl-4-nitrophenyl)-2-(methoxymethyl)piperazine-1-carboxylate Chemical compound C(=O)C1=C(C=CC(=C1)[N+](=O)[O-])N1C[C@@H](N(CC1)C(=O)OC(C)(C)C)COC SKUOYTXUYXQHPC-OAHLLOKOSA-N 0.000 description 2
• QNCXTMZQZFNHKE-LLVKDONJSA-N tert-butyl (2R)-4-(3-fluoro-4-nitrophenyl)-2-methylpiperazine-1-carboxylate Chemical compound FC=1C=C(C=CC=1[N+](=O)[O-])N1C[C@H](N(CC1)C(=O)OC(C)(C)C)C QNCXTMZQZFNHKE-LLVKDONJSA-N 0.000 description 2
• JBSDUXZDLPLFFW-LLVKDONJSA-N tert-butyl (2R)-4-(4-amino-2-fluorophenyl)-2-methylpiperazine-1-carboxylate Chemical compound NC1=CC(=C(C=C1)N1C[C@H](N(CC1)C(=O)OC(C)(C)C)C)F JBSDUXZDLPLFFW-LLVKDONJSA-N 0.000 description 2
• OXGNQZOUVOVRRD-OAHLLOKOSA-N tert-butyl (2R)-4-(4-aminophenyl)-2-(methoxymethyl)piperazine-1-carboxylate Chemical compound NC1=CC=C(C=C1)N1C[C@@H](N(CC1)C(=O)OC(C)(C)C)COC OXGNQZOUVOVRRD-OAHLLOKOSA-N 0.000 description 2
• YCUICQHWPBSAMM-ZRKZCGFPSA-N tert-butyl (2R)-4-[2-(2,2-difluoro-1-hydroxyethyl)-4-nitrophenyl]-2-methylpiperazine-1-carboxylate Chemical compound FC(C(O)C1=C(C=CC(=C1)[N+](=O)[O-])N1C[C@H](N(CC1)C(=O)OC(C)(C)C)C)F YCUICQHWPBSAMM-ZRKZCGFPSA-N 0.000 description 2
• OEYBPNKYHAVXPV-LLVKDONJSA-N tert-butyl (2R)-4-[2-(difluoromethoxy)-4-nitrophenyl]-2-methylpiperazine-1-carboxylate Chemical compound FC(OC1=C(C=CC(=C1)[N+](=O)[O-])N1C[C@H](N(CC1)C(=O)OC(C)(C)C)C)F OEYBPNKYHAVXPV-LLVKDONJSA-N 0.000 description 2
• BATJYFGCMPLPEL-LLVKDONJSA-N tert-butyl (2R)-4-[2-(difluoromethyl)-4-nitrophenyl]-2-methylpiperazine-1-carboxylate Chemical compound FC(C1=C(C=CC(=C1)[N+](=O)[O-])N1C[C@H](N(CC1)C(=O)OC(C)(C)C)C)F BATJYFGCMPLPEL-LLVKDONJSA-N 0.000 description 2
• YWBRAHSVHDKGOY-GFCCVEGCSA-N tert-butyl (2R)-4-[2-(hydroxymethyl)-4-nitrophenyl]-2-methylpiperazine-1-carboxylate Chemical compound OCC1=C(C=CC(=C1)[N+](=O)[O-])N1C[C@H](N(CC1)C(=O)OC(C)(C)C)C YWBRAHSVHDKGOY-GFCCVEGCSA-N 0.000 description 2
• YNORUNOTKBUWLY-CYBMUJFWSA-N tert-butyl (2R)-4-[2-(methoxymethyl)-4-nitrophenyl]-2-methylpiperazine-1-carboxylate Chemical compound COCC1=C(C=CC(=C1)[N+](=O)[O-])N1C[C@H](N(CC1)C(=O)OC(C)(C)C)C YNORUNOTKBUWLY-CYBMUJFWSA-N 0.000 description 2
• ASRCQXKIGJUKPY-OAHLLOKOSA-N tert-butyl (2R)-4-[4-amino-2-(hydroxymethyl)phenyl]-2-(methoxymethyl)piperazine-1-carboxylate Chemical compound NC1=CC(=C(C=C1)N1C[C@@H](N(CC1)C(=O)OC(C)(C)C)COC)CO ASRCQXKIGJUKPY-OAHLLOKOSA-N 0.000 description 2
• KETRKVONSKNJNH-CHWSQXEVSA-N tert-butyl (2R,5R)-2,5-dimethyl-4-(4-nitrophenyl)piperazine-1-carboxylate Chemical compound C[C@H]1N(C[C@H](N(C1)C1=CC=C(C=C1)[N+](=O)[O-])C)C(=O)OC(C)(C)C KETRKVONSKNJNH-CHWSQXEVSA-N 0.000 description 2
• KETRKVONSKNJNH-QWHCGFSZSA-N tert-butyl (2R,5S)-2,5-dimethyl-4-(4-nitrophenyl)piperazine-1-carboxylate Chemical compound C[C@H]1N(C[C@@H](N(C1)C1=CC=C(C=C1)[N+](=O)[O-])C)C(=O)OC(C)(C)C KETRKVONSKNJNH-QWHCGFSZSA-N 0.000 description 2
• MHOYZHJILBQLFT-QWHCGFSZSA-N tert-butyl (2R,5S)-4-(4-aminophenyl)-2,5-dimethylpiperazine-1-carboxylate Chemical compound NC1=CC=C(C=C1)N1C[C@H](N(C[C@@H]1C)C(=O)OC(C)(C)C)C MHOYZHJILBQLFT-QWHCGFSZSA-N 0.000 description 2
• SRRQHCQKLIAFPQ-AWEZNQCLSA-N tert-butyl (2S)-2-(hydroxymethyl)-4-(4-nitrophenyl)piperazine-1-carboxylate Chemical compound OC[C@H]1N(CCN(C1)C1=CC=C(C=C1)[N+](=O)[O-])C(=O)OC(C)(C)C SRRQHCQKLIAFPQ-AWEZNQCLSA-N 0.000 description 2
• DZXJHIBNDMNEHI-LBPRGKRZSA-N tert-butyl (2S)-4-(2-fluoro-4-nitrophenyl)-2-(hydroxymethyl)piperazine-1-carboxylate Chemical compound FC1=C(C=CC(=C1)[N+](=O)[O-])N1C[C@H](N(CC1)C(=O)OC(C)(C)C)CO DZXJHIBNDMNEHI-LBPRGKRZSA-N 0.000 description 2
• DFJWLNIPXWOLMS-LBPRGKRZSA-N tert-butyl (2S)-4-(4-amino-2-fluorophenyl)-2-(hydroxymethyl)piperazine-1-carboxylate Chemical compound NC1=CC(=C(C=C1)N1C[C@H](N(CC1)C(=O)OC(C)(C)C)CO)F DFJWLNIPXWOLMS-LBPRGKRZSA-N 0.000 description 2
• KDBDFFJYINSEQA-GFCCVEGCSA-N tert-butyl (2r)-2-methyl-4-(4-nitrophenyl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)[C@H](C)CN1C1=CC=C([N+]([O-])=O)C=C1 KDBDFFJYINSEQA-GFCCVEGCSA-N 0.000 description 2
• KDBDFFJYINSEQA-LBPRGKRZSA-N tert-butyl (2s)-2-methyl-4-(4-nitrophenyl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)[C@@H](C)CN1C1=CC=C([N+]([O-])=O)C=C1 KDBDFFJYINSEQA-LBPRGKRZSA-N 0.000 description 2
• PGZCVLUQTJRRAA-BDAKNGLRSA-N tert-butyl (2s,5r)-2,5-dimethylpiperazine-1-carboxylate Chemical compound C[C@@H]1CN(C(=O)OC(C)(C)C)[C@@H](C)CN1 PGZCVLUQTJRRAA-BDAKNGLRSA-N 0.000 description 2
• SGTMPRJIQQMTGS-NEPJUHHUSA-N tert-butyl (2s,5r)-4-(2-fluoro-4-nitrophenyl)-2,5-dimethylpiperazine-1-carboxylate Chemical compound C[C@@H]1CN(C(=O)OC(C)(C)C)[C@@H](C)CN1C1=CC=C([N+]([O-])=O)C=C1F SGTMPRJIQQMTGS-NEPJUHHUSA-N 0.000 description 2
• RRKXUQGVCYKPQL-NEPJUHHUSA-N tert-butyl (2s,5r)-4-(4-amino-2-fluorophenyl)-2,5-dimethylpiperazine-1-carboxylate Chemical compound C[C@@H]1CN(C(=O)OC(C)(C)C)[C@@H](C)CN1C1=CC=C(N)C=C1F RRKXUQGVCYKPQL-NEPJUHHUSA-N 0.000 description 2
• AAJUFMWASPADJF-CQSZACIVSA-N tert-butyl (3R)-3-(hydroxymethyl)-4-(4-nitrophenyl)piperazine-1-carboxylate Chemical compound OC[C@H]1CN(CCN1C1=CC=C(C=C1)[N+](=O)[O-])C(=O)OC(C)(C)C AAJUFMWASPADJF-CQSZACIVSA-N 0.000 description 2
• BXFMCRUBXUJSJG-HNNXBMFYSA-N tert-butyl (3S)-3-(methoxymethyl)-4-(4-nitrophenyl)piperazine-1-carboxylate Chemical compound COC[C@@H]1CN(CCN1C1=CC=C(C=C1)[N+](=O)[O-])C(=O)OC(C)(C)C BXFMCRUBXUJSJG-HNNXBMFYSA-N 0.000 description 2
• WNLJFQXUHWUZEN-AWEZNQCLSA-N tert-butyl (3S)-4-(4-aminophenyl)-3-(hydroxymethyl)piperazine-1-carboxylate Chemical compound NC1=CC=C(C=C1)N1[C@@H](CN(CC1)C(=O)OC(C)(C)C)CO WNLJFQXUHWUZEN-AWEZNQCLSA-N 0.000 description 2
• JBMKFLKHSGJWCY-UHFFFAOYSA-N tert-butyl 2-(4-nitrophenyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound C1C2CN(C(=O)OC(C)(C)C)CC2CN1C1=CC=C([N+]([O-])=O)C=C1 JBMKFLKHSGJWCY-UHFFFAOYSA-N 0.000 description 2
• QUKXCTYLOVVEAN-UHFFFAOYSA-N tert-butyl 2-[4-(4-aminophenyl)piperazin-1-yl]acetate Chemical compound CC(C)(C)OC(=O)CN1CCN(CC1)C1=CC=C(N)C=C1 QUKXCTYLOVVEAN-UHFFFAOYSA-N 0.000 description 2
• CLYFFSRCWFLEBS-UHFFFAOYSA-N tert-butyl 2-[4-(4-nitrophenyl)piperazin-1-yl]acetate Chemical compound C1CN(CC(=O)OC(C)(C)C)CCN1C1=CC=C([N+]([O-])=O)C=C1 CLYFFSRCWFLEBS-UHFFFAOYSA-N 0.000 description 2
• HNINFCBLGHCFOJ-UHFFFAOYSA-N tert-butyl 3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound C1NCC2CCC1N2C(=O)OC(C)(C)C HNINFCBLGHCFOJ-UHFFFAOYSA-N 0.000 description 2
• ZQDAZAHYIYEWFH-UHFFFAOYSA-N tert-butyl 3-(2-formyl-4-nitrophenyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound C(=O)C1=C(C=CC(=C1)[N+](=O)[O-])N1CC2CCC(C1)N2C(=O)OC(C)(C)C ZQDAZAHYIYEWFH-UHFFFAOYSA-N 0.000 description 2
• PYEZKRCRVDWREL-UHFFFAOYSA-N tert-butyl 4-(2-formyl-4-nitrophenyl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=C([N+]([O-])=O)C=C1C=O PYEZKRCRVDWREL-UHFFFAOYSA-N 0.000 description 2
• MNAAPQLWAKMBFX-UHFFFAOYSA-N tert-butyl 4-(2-methyl-4-nitrophenyl)piperazine-1-carboxylate Chemical compound CC1=CC([N+]([O-])=O)=CC=C1N1CCN(C(=O)OC(C)(C)C)CC1 MNAAPQLWAKMBFX-UHFFFAOYSA-N 0.000 description 2
• QGSOKWIAGZHFTA-UHFFFAOYSA-N tert-butyl 4-(3-aminoanilino)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1NC1=CC=CC(N)=C1 QGSOKWIAGZHFTA-UHFFFAOYSA-N 0.000 description 2
• ORNLERMGIDBPGR-UHFFFAOYSA-N tert-butyl 4-(3-nitroanilino)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)NC1=CC(=CC=C1)[N+]([O-])=O ORNLERMGIDBPGR-UHFFFAOYSA-N 0.000 description 2
• WEIBGUDKHYWNMW-UHFFFAOYSA-N tert-butyl 4-(4-aminophenoxy)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1OC1=CC=C(N)C=C1 WEIBGUDKHYWNMW-UHFFFAOYSA-N 0.000 description 2
• DHIJQVBFHKCFOC-UHFFFAOYSA-N tert-butyl 4-(4-aminophenyl)-2-(trifluoromethyl)piperazine-1-carboxylate Chemical compound NC1=CC=C(C=C1)N1CC(N(CC1)C(=O)OC(C)(C)C)C(F)(F)F DHIJQVBFHKCFOC-UHFFFAOYSA-N 0.000 description 2
• YRLQFRXDWBFGMK-UHFFFAOYSA-N tert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C1=CC=C(N)C=C1 YRLQFRXDWBFGMK-UHFFFAOYSA-N 0.000 description 2
• UNNMTKGKCWNQNU-UHFFFAOYSA-N tert-butyl 4-(4-nitrophenoxy)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1OC1=CC=C([N+]([O-])=O)C=C1 UNNMTKGKCWNQNU-UHFFFAOYSA-N 0.000 description 2
• XMQWYVSVNPQVNX-UHFFFAOYSA-N tert-butyl 4-(4-nitrophenyl)-2-(trifluoromethyl)piperazine-1-carboxylate Chemical compound [N+](=O)([O-])C1=CC=C(C=C1)N1CC(N(CC1)C(=O)OC(C)(C)C)C(F)(F)F XMQWYVSVNPQVNX-UHFFFAOYSA-N 0.000 description 2
• PKYRLRVLXYAKPM-UHFFFAOYSA-N tert-butyl 4-(4-nitrophenyl)-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC(C=2C=CC(=CC=2)[N+]([O-])=O)=C1 PKYRLRVLXYAKPM-UHFFFAOYSA-N 0.000 description 2
• CTXZMCLNQFLEAT-UHFFFAOYSA-N tert-butyl 4-[2-(chloromethyl)-4-nitrophenyl]piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCN(CC1)C1=C(CCl)C=C(C=C1)[N+]([O-])=O CTXZMCLNQFLEAT-UHFFFAOYSA-N 0.000 description 2
• HAKYMZBYANWLAI-UHFFFAOYSA-N tert-butyl 4-[2-(methoxymethyl)-4-nitrophenyl]piperazine-1-carboxylate Chemical compound COCC1=C(C=CC(=C1)[N+]([O-])=O)N1CCN(CC1)C(=O)OC(C)(C)C HAKYMZBYANWLAI-UHFFFAOYSA-N 0.000 description 2
• HXIJBVWZARSMQN-UHFFFAOYSA-N tert-butyl 4-[4-amino-2-(hydroxymethyl)phenyl]piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCN(CC1)c1ccc(N)cc1CO HXIJBVWZARSMQN-UHFFFAOYSA-N 0.000 description 2
• UYAWNTCEMHWAGP-UHFFFAOYSA-N tert-butyl 5-(4-nitrophenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC2CC1CN2C1=CC=C([N+]([O-])=O)C=C1 UYAWNTCEMHWAGP-UHFFFAOYSA-N 0.000 description 2
• ASKWYJYYKRXENE-UHFFFAOYSA-N tert-butyl 6-(4-nitrophenyl)-2,6-diazaspiro[3.3]heptane-2-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC21CN(C=1C=CC(=CC=1)[N+]([O-])=O)C2 ASKWYJYYKRXENE-UHFFFAOYSA-N 0.000 description 2
• OGPRTHQPTQFNAX-UHFFFAOYSA-N tert-butyl 7-(4-nitrophenyl)-4,7-diazaspiro[2.5]octane-4-carboxylate Chemical compound [N+](=O)([O-])C1=CC=C(C=C1)N1CCN(C2(CC2)C1)C(=O)OC(C)(C)C OGPRTHQPTQFNAX-UHFFFAOYSA-N 0.000 description 2
• AGRBXKCSGCUXST-UHFFFAOYSA-N tert-butyl 7-amino-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound C1=C(N)C=C2CN(C(=O)OC(C)(C)C)CCC2=C1 AGRBXKCSGCUXST-UHFFFAOYSA-N 0.000 description 2
• CQIGVOZVSGSGQU-UHFFFAOYSA-N tert-butyl N-[(5-amino-2-pyrrolidin-1-ylphenyl)methyl]-N-methylcarbamate Chemical compound NC=1C=CC(=C(CN(C(OC(C)(C)C)=O)C)C=1)N1CCCC1 CQIGVOZVSGSGQU-UHFFFAOYSA-N 0.000 description 2
• WPGUINCXJXESFG-UHFFFAOYSA-N tert-butyl N-[[2-(4-acetylpiperazin-1-yl)-5-aminophenyl]methyl]-N-methylcarbamate Chemical compound C(C)(=O)N1CCN(CC1)C1=C(CN(C(OC(C)(C)C)=O)C)C=C(C=C1)N WPGUINCXJXESFG-UHFFFAOYSA-N 0.000 description 2
• GTDQVMBZKMCBMV-UHFFFAOYSA-N tert-butyl N-methyl-N-[(2-morpholin-4-yl-5-nitrophenyl)methyl]carbamate Chemical compound CN(C(OC(C)(C)C)=O)CC1=C(C=CC(=C1)[N+](=O)[O-])N1CCOCC1 GTDQVMBZKMCBMV-UHFFFAOYSA-N 0.000 description 2
• CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 2
• JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 2
• 125000003831 tetrazolyl group Chemical group 0.000 description 2
• 125000001544 thienyl group Chemical group 0.000 description 2
• WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 2
• 229940044693 topoisomerase inhibitor Drugs 0.000 description 2
• 231100000419 toxicity Toxicity 0.000 description 2
• 230000001988 toxicity Effects 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
• 229910052905 tridymite Inorganic materials 0.000 description 2
• 210000004881 tumor cell Anatomy 0.000 description 2
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
• 238000005406 washing Methods 0.000 description 2
• YKPQUSLRUFLVDA-UHFFFAOYSA-N $l^{2}-azanylmethane Chemical compound [NH]C YKPQUSLRUFLVDA-UHFFFAOYSA-N 0.000 description 1
• VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
• IFNWESYYDINUHV-OLQVQODUSA-N (2s,6r)-2,6-dimethylpiperazine Chemical compound C[C@H]1CNC[C@@H](C)N1 IFNWESYYDINUHV-OLQVQODUSA-N 0.000 description 1
• OJZQOQNSUZLSMV-UHFFFAOYSA-N (3-aminophenyl)methanol Chemical compound NC1=CC=CC(CO)=C1 OJZQOQNSUZLSMV-UHFFFAOYSA-N 0.000 description 1
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 1
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
• LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical compound C([C@@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-KRWDZBQOSA-N 0.000 description 1
• MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
• RFAPOGMFZTYBEW-UHFFFAOYSA-N 1,2,2-trimethylpiperazine Chemical compound CN1CCNCC1(C)C RFAPOGMFZTYBEW-UHFFFAOYSA-N 0.000 description 1
• 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 description 1
• 125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 description 1
• 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 1
• 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 description 1
• 125000004530 1,2,4-triazinyl group Chemical group N1=NC(=NC=C1)* 0.000 description 1
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
• 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 1
• 125000000196 1,4-pentadienyl group Chemical group [H]C([*])=C([H])C([H])([H])C([H])=C([H])[H] 0.000 description 1
• NVKGVBZZSJFQLM-UHFFFAOYSA-N 1-(2-chloroethyl)-1-nitrosourea Chemical compound NC(=O)N(N=O)CCCl NVKGVBZZSJFQLM-UHFFFAOYSA-N 0.000 description 1
• BMEMBBFDTYHTLH-UHFFFAOYSA-N 1-(2-methoxyethyl)piperazine Chemical compound COCCN1CCNCC1 BMEMBBFDTYHTLH-UHFFFAOYSA-N 0.000 description 1
• IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 description 1
• VWOJSRICSKDKAW-UHFFFAOYSA-N 1-(4-nitrophenyl)piperazine Chemical compound C1=CC([N+](=O)[O-])=CC=C1N1CCNCC1 VWOJSRICSKDKAW-UHFFFAOYSA-N 0.000 description 1
• FDPNLXVYBLUXLK-UHFFFAOYSA-N 1-[4-[4-amino-2-[(dimethylamino)methyl]phenyl]piperazin-1-yl]ethanone Chemical compound NC1=CC(=C(C=C1)N1CCN(CC1)C(C)=O)CN(C)C FDPNLXVYBLUXLK-UHFFFAOYSA-N 0.000 description 1
• HHCLNZBCCQDVOQ-UHFFFAOYSA-N 1-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]pyrazol-3-yl]methyl]piperazin-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(N1CC2=C(CC1)NN=N2)=O)CN1C(CNCC1)=O HHCLNZBCCQDVOQ-UHFFFAOYSA-N 0.000 description 1
• ZDFBKZUDCQQKAC-UHFFFAOYSA-N 1-bromo-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Br)C=C1 ZDFBKZUDCQQKAC-UHFFFAOYSA-N 0.000 description 1
• 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
• 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
• HNZJIWIXRPBFAN-UHFFFAOYSA-N 1-cyclopropylpiperazine Chemical compound C1CC1N1CCNCC1 HNZJIWIXRPBFAN-UHFFFAOYSA-N 0.000 description 1
• WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 description 1
• AZNKKZHZGDZSIF-UHFFFAOYSA-N 1-fluoro-2-methoxy-4-nitrobenzene Chemical compound COC1=CC([N+]([O-])=O)=CC=C1F AZNKKZHZGDZSIF-UHFFFAOYSA-N 0.000 description 1
• MOGQNVSKBCVIPW-UHFFFAOYSA-N 1-methylpyrazol-3-amine Chemical compound CN1C=CC(N)=N1 MOGQNVSKBCVIPW-UHFFFAOYSA-N 0.000 description 1
• PKDPUENCROCRCH-UHFFFAOYSA-N 1-piperazin-1-ylethanone Chemical compound CC(=O)N1CCNCC1 PKDPUENCROCRCH-UHFFFAOYSA-N 0.000 description 1
• WHKWMTXTYKVFLK-UHFFFAOYSA-N 1-propan-2-ylpiperazine Chemical compound CC(C)N1CCNCC1 WHKWMTXTYKVFLK-UHFFFAOYSA-N 0.000 description 1
• 125000006017 1-propenyl group Chemical group 0.000 description 1
• 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
• IAAQUOVTPAMQCR-UHFFFAOYSA-N 1h-pyrido[3,2-d]pyrimidin-2-one Chemical class C1=CC=C2NC(=O)N=CC2=N1 IAAQUOVTPAMQCR-UHFFFAOYSA-N 0.000 description 1
• KIPSRYDSZQRPEA-UHFFFAOYSA-N 2,2,2-trifluoroethanamine Chemical compound NCC(F)(F)F KIPSRYDSZQRPEA-UHFFFAOYSA-N 0.000 description 1
• YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
• ARDYHOMYWMROCB-UHFFFAOYSA-N 2,4-dichloro-n-(2,6-dichlorophenyl)pyrimidine-5-carboxamide Chemical compound ClC1=NC(Cl)=NC=C1C(=O)NC1=C(Cl)C=CC=C1Cl ARDYHOMYWMROCB-UHFFFAOYSA-N 0.000 description 1
• RJXOVESYJFXCGI-UHFFFAOYSA-N 2,4-difluoro-1-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1F RJXOVESYJFXCGI-UHFFFAOYSA-N 0.000 description 1
• KVTRUBZAMRIDHX-UHFFFAOYSA-N 2,5-diazabicyclo[2.2.1]heptane-2-carboxylic acid Chemical compound C1C2N(C(=O)O)CC1NC2 KVTRUBZAMRIDHX-UHFFFAOYSA-N 0.000 description 1
• KAZCRAZAPYLBLI-UHFFFAOYSA-N 2-(12-azatricyclo[7.2.1.02,7]dodeca-2(7),3,5-trien-4-ylamino)-6-(2,6-dichlorophenyl)-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC2=C(CC3CCC2N3)C=C1)C KAZCRAZAPYLBLI-UHFFFAOYSA-N 0.000 description 1
• YNEJOOCZWXGXDU-UHFFFAOYSA-N 2-(trifluoromethyl)piperazine Chemical compound FC(F)(F)C1CNCCN1 YNEJOOCZWXGXDU-UHFFFAOYSA-N 0.000 description 1
• VRPJIFMKZZEXLR-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical compound CC(C)(C)OC(=O)NCC(O)=O VRPJIFMKZZEXLR-UHFFFAOYSA-N 0.000 description 1
• RSZDSSUZZYDOFU-UHFFFAOYSA-N 2-[4-(2,5-diazabicyclo[2.2.1]heptan-2-yl)anilino]-6-(2,6-dichlorophenyl)-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound C12N(CC(NC1)C2)C1=CC=C(C=C1)NC1=NC=C2C(=N1)N(CN(C2=O)C1=C(C=CC=C1Cl)Cl)C RSZDSSUZZYDOFU-UHFFFAOYSA-N 0.000 description 1
• MPSDZSSVMJBCCW-HOTGVXAUSA-N 2-[4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl]-3-methoxyanilino]-6-(2,6-dichlorophenyl)-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound COc1cc(Nc2ncc3C(=O)N(CN(C)c3n2)c2c(Cl)cccc2Cl)ccc1N1C[C@@H]2C[C@H]1CN2 MPSDZSSVMJBCCW-HOTGVXAUSA-N 0.000 description 1
• YRXIMPFOTQVOHG-UHFFFAOYSA-N 2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]acetic acid Chemical compound OC(=O)CN(C)C(=O)OC(C)(C)C YRXIMPFOTQVOHG-UHFFFAOYSA-N 0.000 description 1
• MJLVLHNXEOQASX-UHFFFAOYSA-M 2-bromo-3,3-dimethylbutanoate Chemical compound CC(C)(C)C(Br)C([O-])=O MJLVLHNXEOQASX-UHFFFAOYSA-M 0.000 description 1
• KNJNITQHVLIWBN-UHFFFAOYSA-N 2-bromo-5-nitrophenol Chemical compound OC1=CC([N+]([O-])=O)=CC=C1Br KNJNITQHVLIWBN-UHFFFAOYSA-N 0.000 description 1
• 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
• UKCWRSLJMIVBDE-UHFFFAOYSA-N 2-chloro-3-(2,6-dichlorophenyl)-6-(4-hydroxybutylimino)-1,2-dihydropyrimidine-5-carboxamide Chemical compound ClC1N(C=C(C(=N1)NCCCCO)C(=O)N)C1=C(C=CC=C1Cl)Cl UKCWRSLJMIVBDE-UHFFFAOYSA-N 0.000 description 1
• ZJLAWMDJTMMTQB-UHFFFAOYSA-N 2-chloro-6-fluoroaniline Chemical compound NC1=C(F)C=CC=C1Cl ZJLAWMDJTMMTQB-UHFFFAOYSA-N 0.000 description 1
• WFNLHDJJZSJARK-UHFFFAOYSA-N 2-chloro-6-methylaniline Chemical compound CC1=CC=CC(Cl)=C1N WFNLHDJJZSJARK-UHFFFAOYSA-N 0.000 description 1
• RBMUIOVGWVIGAV-UHFFFAOYSA-N 2-chloro-N-(2,6-dichlorophenyl)-4-(4-hydroxybutylamino)pyrimidine-5-carboxamide Chemical compound OCCCCNC1=C(C=NC(Cl)=N1)C(=O)NC1=C(Cl)C=CC=C1Cl RBMUIOVGWVIGAV-UHFFFAOYSA-N 0.000 description 1
• AKCRQHGQIJBRMN-UHFFFAOYSA-N 2-chloroaniline Chemical compound NC1=CC=CC=C1Cl AKCRQHGQIJBRMN-UHFFFAOYSA-N 0.000 description 1
• WZCSDKGSAQJQLS-UHFFFAOYSA-N 2-methylspiro[1,3-dihydroisoquinoline-4,1'-cyclopropane]-7-amine;dihydrochloride Chemical compound Cl.Cl.C1N(C)CC2=CC(N)=CC=C2C21CC2 WZCSDKGSAQJQLS-UHFFFAOYSA-N 0.000 description 1
• WFCSWCVEJLETKA-UHFFFAOYSA-N 2-piperazin-1-ylethanol Chemical compound OCCN1CCNCC1 WFCSWCVEJLETKA-UHFFFAOYSA-N 0.000 description 1
• HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
• BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
• WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
• 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
• 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
• XJCVRTZCHMZPBD-UHFFFAOYSA-N 3-nitroaniline Chemical compound NC1=CC=CC([N+]([O-])=O)=C1 XJCVRTZCHMZPBD-UHFFFAOYSA-N 0.000 description 1
• BWFFUVHIMDAFBQ-UHFFFAOYSA-N 4-(4-aminophenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid Chemical compound NC1=CC=C(C=C1)C=1CCN(CC1)C(=O)O BWFFUVHIMDAFBQ-UHFFFAOYSA-N 0.000 description 1
• WNYFVEFUHMDIRQ-UHFFFAOYSA-N 4-(morpholin-4-ylmethyl)aniline Chemical compound C1=CC(N)=CC=C1CN1CCOCC1 WNYFVEFUHMDIRQ-UHFFFAOYSA-N 0.000 description 1
• DJVJJFDZNRYSHR-SECBINFHSA-N 4-[(3r)-3-methylpiperazin-1-yl]aniline Chemical compound C1CN[C@H](C)CN1C1=CC=C(N)C=C1 DJVJJFDZNRYSHR-SECBINFHSA-N 0.000 description 1
• KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
• BLFRQYKZFKYQLO-UHFFFAOYSA-N 4-aminobutan-1-ol Chemical compound NCCCCO BLFRQYKZFKYQLO-UHFFFAOYSA-N 0.000 description 1
• PHNDZBFLOPIMSM-UHFFFAOYSA-N 4-morpholin-4-ylaniline Chemical compound C1=CC(N)=CC=C1N1CCOCC1 PHNDZBFLOPIMSM-UHFFFAOYSA-N 0.000 description 1
• 125000002471 4H-quinolizinyl group Chemical group C=1(C=CCN2C=CC=CC12)* 0.000 description 1
• BINKTJGGJWWMCG-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-(4-piperazin-1-ylanilino)-7,8-dihydropyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CNC2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1CCNCC1 BINKTJGGJWWMCG-UHFFFAOYSA-N 0.000 description 1
• BMMBSYZVMLJDPP-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[3-(hydroxymethyl)-4-(4-methylpiperazin-1-yl)anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1CCN(CC1)C)CO)C BMMBSYZVMLJDPP-UHFFFAOYSA-N 0.000 description 1
• OTZUTQFGFIDOJK-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-2-[4-(4-ethylpiperazin-1-yl)-3-(hydroxymethyl)anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC(=C(C=C1)N1CCN(CC1)CC)CO)C OTZUTQFGFIDOJK-UHFFFAOYSA-N 0.000 description 1
• KORCVBOCKBZMRD-MRXNPFEDSA-N 6-(2,6-dichlorophenyl)-2-[4-[(3R)-3,4-dimethylpiperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1C[C@H](N(CC1)C)C)C KORCVBOCKBZMRD-MRXNPFEDSA-N 0.000 description 1
• DADTZPCBJDBNMI-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-[4-(2-methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl)anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1CC2CN(CC2C1)C)C DADTZPCBJDBNMI-UHFFFAOYSA-N 0.000 description 1
• UQDMIKNTAOFTPR-UHFFFAOYSA-N 6-(2,6-dichlorophenyl)-8-methyl-2-methylsulfanyl-7-phenyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1C(N(C2=NC(=NC=C2C1=O)SC)C)C1=CC=CC=C1 UQDMIKNTAOFTPR-UHFFFAOYSA-N 0.000 description 1
• WLKZQDLEOHXADE-OAHLLOKOSA-N 6-(2-chloro-6-fluorophenyl)-8-methyl-2-[4-[(3R)-3-methylpiperazin-1-yl]anilino]-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C(=CC=C1)F)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1C[C@H](NCC1)C)C WLKZQDLEOHXADE-OAHLLOKOSA-N 0.000 description 1
• PPBJDFCSIBBTIQ-UHFFFAOYSA-N 6-(2-chloro-6-methylphenyl)-2-[4-(3,8-diazabicyclo[3.2.1]octan-3-yl)-3-(hydroxymethyl)anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound C12CN(CC(CC1)N2)C1=C(C=C(C=C1)NC1=NC=C2C(=N1)N(CN(C2=O)C1=C(C=CC=C1C)Cl)C)CO PPBJDFCSIBBTIQ-UHFFFAOYSA-N 0.000 description 1
• RKIXTYPQCGYFSZ-UHFFFAOYSA-N 6-(2-chlorophenyl)-2-[4-(4,7-diazaspiro[2.5]octan-7-yl)anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound C1CC11NCCN(C1)C1=CC=C(C=C1)NC1=NC=C2C(=N1)N(CN(C2=O)C1=C(C=CC=C1)Cl)C RKIXTYPQCGYFSZ-UHFFFAOYSA-N 0.000 description 1
• PERJRGDWNPTLCF-SJORKVTESA-N 6-(2-chlorophenyl)-2-[4-[(2S,5R)-2,5-dimethylpiperazin-1-yl]anilino]-8-methyl-7H-pyrimido[4,5-d]pyrimidin-5-one Chemical compound ClC1=C(C=CC=C1)N1CN(C2=NC(=NC=C2C1=O)NC1=CC=C(C=C1)N1[C@H](CN[C@@H](C1)C)C)C PERJRGDWNPTLCF-SJORKVTESA-N 0.000 description 1
• KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
• ZSQBZADJUMJJAA-UHFFFAOYSA-N 7-(2,6-dichlorophenyl)-12-(4-piperazin-1-ylanilino)-2,7,11,13-tetrazatricyclo[7.4.0.02,6]trideca-1(13),9,11-trien-8-one Chemical compound ClC1=C(C(=CC=C1)Cl)N1C2N(C3=C(C1=O)C=NC(=N3)NC1=CC=C(C=C1)N1CCNCC1)CCC2 ZSQBZADJUMJJAA-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 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 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• 108090000433 Aurora kinases Proteins 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
• 206010005949 Bone cancer Diseases 0.000 description 1
• 208000018084 Bone neoplasm Diseases 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 1
• GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 description 1
• GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• 229920000742 Cotton Polymers 0.000 description 1
• 108050006400 Cyclin Proteins 0.000 description 1
• 102000016736 Cyclin Human genes 0.000 description 1
• 102000002427 Cyclin B Human genes 0.000 description 1
• 108010068150 Cyclin B Proteins 0.000 description 1
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
• HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
• GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 1
• ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 description 1
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 101100457919 Drosophila melanogaster stg gene Proteins 0.000 description 1
• 241000463291 Elga Species 0.000 description 1
• 239000001856 Ethyl cellulose Substances 0.000 description 1
• ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
• 241000400611 Eucalyptus deanei Species 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
• 230000010190 G1 phase Effects 0.000 description 1
• 230000020172 G2/M transition checkpoint Effects 0.000 description 1
• 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• 208000017604 Hodgkin disease Diseases 0.000 description 1
• 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101001047090 Homo sapiens Potassium voltage-gated channel subfamily H member 2 Proteins 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
• 239000005517 L01XE01 - Imatinib Substances 0.000 description 1
• 239000005411 L01XE02 - Gefitinib Substances 0.000 description 1
• 239000005551 L01XE03 - Erlotinib Substances 0.000 description 1
• 239000002147 L01XE04 - Sunitinib Substances 0.000 description 1
• 239000005511 L01XE05 - Sorafenib Substances 0.000 description 1
• 239000002067 L01XE06 - Dasatinib Substances 0.000 description 1
• 239000002136 L01XE07 - Lapatinib Substances 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• 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 1
• 102000009151 Luteinizing Hormone Human genes 0.000 description 1
• 108010073521 Luteinizing Hormone Proteins 0.000 description 1
• 206010025323 Lymphomas Diseases 0.000 description 1
• 206010027406 Mesothelioma Diseases 0.000 description 1
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
• 208000034578 Multiple myelomas Diseases 0.000 description 1
• WSSWVOXXPPYGPE-UHFFFAOYSA-N N-(2,6-dichlorophenyl)-4-[(1-methylpyrazol-3-yl)amino]-2-methylsulfanylpyrimidine-5-carboxamide Chemical compound CSC1=NC(NC2=NN(C)C=C2)=C(C=N1)C(=O)NC1=C(Cl)C=CC=C1Cl WSSWVOXXPPYGPE-UHFFFAOYSA-N 0.000 description 1
• AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
• ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
• UQFQONCQIQEYPJ-UHFFFAOYSA-N N-methylpyrazole Chemical compound CN1C=CC=N1 UQFQONCQIQEYPJ-UHFFFAOYSA-N 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• ZAHXYMFVNNUHCP-UHFFFAOYSA-N Naphazoline nitrate Chemical group O[N+]([O-])=O.C=1C=CC2=CC=CC=C2C=1CC1=NCCN1 ZAHXYMFVNNUHCP-UHFFFAOYSA-N 0.000 description 1
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 229930012538 Paclitaxel Natural products 0.000 description 1
• 229910002666 PdCl2 Inorganic materials 0.000 description 1
• 206010035226 Plasma cell myeloma Diseases 0.000 description 1
• 108030005449 Polo kinases Proteins 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 102100022807 Potassium voltage-gated channel subfamily H member 2 Human genes 0.000 description 1
• 229940079156 Proteasome inhibitor Drugs 0.000 description 1
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
• 229910004298 SiO 2 Inorganic materials 0.000 description 1
• 208000000453 Skin Neoplasms Diseases 0.000 description 1
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
• 239000004133 Sodium thiosulphate Substances 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• 229940123237 Taxane Drugs 0.000 description 1
• FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
• 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
• 241000209140 Triticum Species 0.000 description 1
• 235000021307 Triticum Nutrition 0.000 description 1
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
• JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
• 229940122803 Vinca alkaloid Drugs 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
• LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 239000004480 active ingredient Substances 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 230000002730 additional effect Effects 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• 229960000548 alemtuzumab Drugs 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 150000001342 alkaline earth metals Chemical class 0.000 description 1
• 125000003282 alkyl amino group Chemical group 0.000 description 1
• 125000004414 alkyl thio group Chemical group 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• WMGSQTMJHBYJMQ-UHFFFAOYSA-N aluminum;magnesium;silicate Chemical compound [Mg+2].[Al+3].[O-][Si]([O-])([O-])[O-] WMGSQTMJHBYJMQ-UHFFFAOYSA-N 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• 229960002932 anastrozole Drugs 0.000 description 1
• YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 description 1
• 239000004037 angiogenesis inhibitor Substances 0.000 description 1
• 239000005557 antagonist Substances 0.000 description 1
• 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
• 229940045799 anthracyclines and related substance Drugs 0.000 description 1
• 230000002280 anti-androgenic effect Effects 0.000 description 1
• 230000001093 anti-cancer Effects 0.000 description 1
• 229940046836 anti-estrogen Drugs 0.000 description 1
• 230000001833 anti-estrogenic effect Effects 0.000 description 1
• 239000000051 antiandrogen Substances 0.000 description 1
• 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
• 239000003080 antimitotic agent Substances 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 230000003078 antioxidant effect Effects 0.000 description 1
• 230000001640 apoptogenic effect Effects 0.000 description 1
• 125000004659 aryl alkyl thio group Chemical group 0.000 description 1
• 125000002102 aryl alkyloxo group Chemical group 0.000 description 1
• 125000001769 aryl amino group Chemical group 0.000 description 1
• 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
• 125000005110 aryl thio group Chemical group 0.000 description 1
• 125000004104 aryloxy group Chemical group 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 239000005441 aurora Substances 0.000 description 1
• 239000002585 base Substances 0.000 description 1
• 150000007514 bases Chemical class 0.000 description 1
• YTKUWDBFDASYHO-UHFFFAOYSA-N bendamustine Chemical compound ClCCN(CCCl)C1=CC=C2N(C)C(CCCC(O)=O)=NC2=C1 YTKUWDBFDASYHO-UHFFFAOYSA-N 0.000 description 1
• 229960002707 bendamustine Drugs 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000004602 benzodiazinyl group Chemical group N1=NC(=CC2=C1C=CC=C2)* 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000004599 benzpyrazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 235000019445 benzyl alcohol Nutrition 0.000 description 1
• 229960000397 bevacizumab Drugs 0.000 description 1
• 229960000997 bicalutamide Drugs 0.000 description 1
• BVCRERJDOOBZOH-UHFFFAOYSA-N bicyclo[2.2.1]heptanyl Chemical group C1C[C+]2CC[C-]1C2 BVCRERJDOOBZOH-UHFFFAOYSA-N 0.000 description 1
• 210000000013 bile duct Anatomy 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000008236 biological pathway Effects 0.000 description 1
• 239000000090 biomarker Substances 0.000 description 1
• 230000015572 biosynthetic process Effects 0.000 description 1
• 230000002051 biphasic effect Effects 0.000 description 1
• 210000000988 bone and bone Anatomy 0.000 description 1
• 229960001467 bortezomib Drugs 0.000 description 1
• GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 description 1
• 210000000133 brain stem Anatomy 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 239000006172 buffering agent Substances 0.000 description 1
• 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 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
• 229940127093 camptothecin Drugs 0.000 description 1
• 229960004117 capecitabine Drugs 0.000 description 1
• 150000001720 carbohydrates Chemical class 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 150000007942 carboxylates Chemical class 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 150000001768 cations Chemical class 0.000 description 1
• 101150069072 cdc25 gene Proteins 0.000 description 1
• 230000012820 cell cycle checkpoint Effects 0.000 description 1
• 230000023359 cell cycle switching, meiotic to mitotic cell cycle Effects 0.000 description 1
• 230000030833 cell death Effects 0.000 description 1
• 230000010261 cell growth Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• 210000003679 cervix uteri Anatomy 0.000 description 1
• 229960005395 cetuximab Drugs 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 239000003153 chemical reaction reagent Substances 0.000 description 1
• 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
• 238000011260 co-administration Methods 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 210000001072 colon Anatomy 0.000 description 1
• 239000012230 colorless oil Substances 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 210000002808 connective tissue Anatomy 0.000 description 1
• 235000005822 corn Nutrition 0.000 description 1
• 230000002596 correlated effect Effects 0.000 description 1
• 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
• 125000003678 cyclohexadienyl group Chemical group C1(=CC=CCC1)* 0.000 description 1
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
• 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
• 229960004397 cyclophosphamide Drugs 0.000 description 1
• 229960002448 dasatinib Drugs 0.000 description 1
• 125000004855 decalinyl group Chemical group C1(CCCC2CCCCC12)* 0.000 description 1
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 238000010511 deprotection reaction Methods 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 125000005331 diazinyl group Chemical group N1=NC(=CC=C1)* 0.000 description 1
• WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 1
• FJBFPHVGVWTDIP-DICFDUPASA-N dibromo(dideuterio)methane Chemical compound [2H]C([2H])(Br)Br FJBFPHVGVWTDIP-DICFDUPASA-N 0.000 description 1
• 235000014113 dietary fatty acids Nutrition 0.000 description 1
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Substances CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 1
• OOKFLLNDYNWCHK-UHFFFAOYSA-N difluoromethyl(trimethyl)silane Chemical compound C[Si](C)(C)C(F)F OOKFLLNDYNWCHK-UHFFFAOYSA-N 0.000 description 1
• 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 1
• 125000004639 dihydroindenyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 1
• 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 description 1
• 125000005057 dihydrothienyl group Chemical group S1C(CC=C1)* 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 1
• 229960003668 docetaxel Drugs 0.000 description 1
• POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
• 239000003937 drug carrier Substances 0.000 description 1
• 239000000890 drug combination Substances 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Natural products C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 1
• 230000002357 endometrial effect Effects 0.000 description 1
• 210000000981 epithelium Anatomy 0.000 description 1
• 229930013356 epothilone Natural products 0.000 description 1
• HESCAJZNRMSMJG-KKQRBIROSA-N epothilone A Chemical class C/C([C@@H]1C[C@@H]2O[C@@H]2CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 HESCAJZNRMSMJG-KKQRBIROSA-N 0.000 description 1
• 229960001433 erlotinib Drugs 0.000 description 1
• AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 1
• 210000003238 esophagus Anatomy 0.000 description 1
• 239000000328 estrogen antagonist Substances 0.000 description 1
• GVCAWQUJCHZRCB-UHFFFAOYSA-N ethyl 2-chloro-2,2-difluoroacetate Chemical compound CCOC(=O)C(F)(F)Cl GVCAWQUJCHZRCB-UHFFFAOYSA-N 0.000 description 1
• UJIPWFPJAVYMHV-UHFFFAOYSA-N ethyl 2-fluoro-5-nitrobenzoate Chemical compound CCOC(=O)C1=CC([N+]([O-])=O)=CC=C1F UJIPWFPJAVYMHV-UHFFFAOYSA-N 0.000 description 1
• SNNHLSHDDGJVDM-UHFFFAOYSA-N ethyl 4-chloro-2-methylsulfanylpyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(SC)N=C1Cl SNNHLSHDDGJVDM-UHFFFAOYSA-N 0.000 description 1
• 235000019325 ethyl cellulose Nutrition 0.000 description 1
• 229920001249 ethyl cellulose Polymers 0.000 description 1
• IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 125000006125 ethylsulfonyl group Chemical group 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 239000003925 fat Substances 0.000 description 1
• 239000000194 fatty acid Substances 0.000 description 1
• 229930195729 fatty acid Natural products 0.000 description 1
• 150000004665 fatty acids Chemical class 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 229960000390 fludarabine Drugs 0.000 description 1
• GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 1
• 229960002074 flutamide Drugs 0.000 description 1
• MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
• PTCGDEVVHUXTMP-UHFFFAOYSA-N flutolanil Chemical compound CC(C)OC1=CC=CC(NC(=O)C=2C(=CC=CC=2)C(F)(F)F)=C1 PTCGDEVVHUXTMP-UHFFFAOYSA-N 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 210000000232 gallbladder Anatomy 0.000 description 1
• 229960002584 gefitinib Drugs 0.000 description 1
• XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 230000030279 gene silencing Effects 0.000 description 1
• 210000004907 gland Anatomy 0.000 description 1
• 229910052736 halogen Inorganic materials 0.000 description 1
• 150000002367 halogens Chemical class 0.000 description 1
• 210000003128 head Anatomy 0.000 description 1
• 208000024348 heart neoplasm Diseases 0.000 description 1
• 230000002489 hematologic effect Effects 0.000 description 1
• 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 239000008241 heterogeneous mixture Substances 0.000 description 1
• 125000006038 hexenyl group Chemical group 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 229940121372 histone deacetylase inhibitor Drugs 0.000 description 1
• 239000003276 histone deacetylase inhibitor Substances 0.000 description 1
• 238000001794 hormone therapy Methods 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
• 235000010979 hydroxypropyl methyl cellulose Nutrition 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
• 210000003026 hypopharynx Anatomy 0.000 description 1
• 239000005457 ice water Substances 0.000 description 1
• HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
• 229960001101 ifosfamide Drugs 0.000 description 1
• KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 1
• 229960002411 imatinib Drugs 0.000 description 1
• 125000002632 imidazolidinyl group Chemical group 0.000 description 1
• 125000002636 imidazolinyl group Chemical group 0.000 description 1
• 229940127121 immunoconjugate Drugs 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
• 238000004255 ion exchange chromatography Methods 0.000 description 1
• 150000008040 ionic compounds Chemical class 0.000 description 1
• RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 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
• 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 1
• 125000005438 isoindazolyl group Chemical group 0.000 description 1
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 125000005956 isoquinolyl group Chemical group 0.000 description 1
• 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
• 125000005969 isothiazolinyl group Chemical group 0.000 description 1
• 125000003965 isoxazolidinyl group Chemical group 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 229960004891 lapatinib Drugs 0.000 description 1
• BCFGMOOMADDAQU-UHFFFAOYSA-N lapatinib Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 BCFGMOOMADDAQU-UHFFFAOYSA-N 0.000 description 1
• 210000000867 larynx Anatomy 0.000 description 1
• 229940070765 laurate Drugs 0.000 description 1
• 229960003881 letrozole Drugs 0.000 description 1
• HPJKCIUCZWXJDR-UHFFFAOYSA-N letrozole Chemical compound C1=CC(C#N)=CC=C1C(N1N=CN=C1)C1=CC=C(C#N)C=C1 HPJKCIUCZWXJDR-UHFFFAOYSA-N 0.000 description 1
• 208000032839 leukemia Diseases 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 208000014018 liver neoplasm Diseases 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 208000020816 lung neoplasm Diseases 0.000 description 1
• 229940040129 luteinizing hormone Drugs 0.000 description 1
• 239000000395 magnesium oxide Substances 0.000 description 1
• CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
• AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 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
• 238000001819 mass spectrum Methods 0.000 description 1
• 239000000463 material Substances 0.000 description 1
• 201000000349 mediastinal cancer Diseases 0.000 description 1
• SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
• 229960001924 melphalan Drugs 0.000 description 1
• 229960001428 mercaptopurine Drugs 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
• OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 1
• 229960000485 methotrexate Drugs 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
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 230000000394 mitotic effect Effects 0.000 description 1
• 238000002156 mixing Methods 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
• GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 210000003928 nasal cavity Anatomy 0.000 description 1
• 210000003739 neck Anatomy 0.000 description 1
• 208000018280 neoplasm of mediastinum Diseases 0.000 description 1
• 201000011682 nervous system cancer Diseases 0.000 description 1
• 201000011519 neuroendocrine tumor Diseases 0.000 description 1
• 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
• 231100000344 non-irritating Toxicity 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 229940049964 oleate Drugs 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 238000011275 oncology therapy Methods 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 239000011368 organic material Substances 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 210000003300 oropharynx Anatomy 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 230000002018 overexpression Effects 0.000 description 1
• 229960001756 oxaliplatin Drugs 0.000 description 1
• DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
• 125000005880 oxathiolanyl group Chemical group 0.000 description 1
• 125000000160 oxazolidinyl group Chemical group 0.000 description 1
• 229910052760 oxygen Inorganic materials 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 229950007318 ozogamicin Drugs 0.000 description 1
• 229960001592 paclitaxel Drugs 0.000 description 1
• PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
• 150000002942 palmitic acid derivatives Chemical class 0.000 description 1
• 210000000496 pancreas Anatomy 0.000 description 1
• 229960001972 panitumumab Drugs 0.000 description 1
• QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
• 230000000849 parathyroid Effects 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• WBXPDJSOTKVWSJ-ZDUSSCGKSA-N pemetrexed Chemical compound C=1NC=2NC(N)=NC(=O)C=2C=1CCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 WBXPDJSOTKVWSJ-ZDUSSCGKSA-N 0.000 description 1
• 210000003899 penis Anatomy 0.000 description 1
• 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
• 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
• 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 230000001817 pituitary effect Effects 0.000 description 1
• IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
• 150000003057 platinum Chemical class 0.000 description 1
• 229910052697 platinum Inorganic materials 0.000 description 1
• 229920001515 polyalkylene glycol Polymers 0.000 description 1
• 229920005862 polyol Polymers 0.000 description 1
• 150000003077 polyols Chemical class 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 238000002360 preparation method Methods 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
• 208000023958 prostate neoplasm Diseases 0.000 description 1
• 239000003207 proteasome inhibitor Substances 0.000 description 1
• 238000000425 proton nuclear magnetic resonance spectrum Methods 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
• 125000005412 pyrazyl group Chemical group 0.000 description 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
• 125000001422 pyrrolinyl group Chemical group 0.000 description 1
• 125000005493 quinolyl group Chemical group 0.000 description 1
• 150000003254 radicals Chemical class 0.000 description 1
• 230000000637 radiosensitizating effect Effects 0.000 description 1
• GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 1
• 229960004622 raloxifene Drugs 0.000 description 1
• 210000000664 rectum Anatomy 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 239000013557 residual solvent Substances 0.000 description 1
• 229940100486 rice starch Drugs 0.000 description 1
• 229960004641 rituximab Drugs 0.000 description 1
• HNMATTJJEPZZMM-BPKVFSPJSA-N s-[(2r,3s,4s,6s)-6-[[(2r,3s,4s,5r,6r)-5-[(2s,4s,5s)-5-[acetyl(ethyl)amino]-4-methoxyoxan-2-yl]oxy-6-[[(2s,5z,9r,13e)-13-[2-[[4-[(2e)-2-[1-[4-(4-amino-4-oxobutoxy)phenyl]ethylidene]hydrazinyl]-2-methyl-4-oxobutan-2-yl]disulfanyl]ethylidene]-9-hydroxy-12-(m Chemical compound C1[C@H](OC)[C@@H](N(CC)C(C)=O)CO[C@H]1O[C@H]1[C@H](O[C@@H]2C\3=C(NC(=O)OC)C(=O)C[C@@](C/3=C/CSSC(C)(C)CC(=O)N\N=C(/C)C=3C=CC(OCCCC(N)=O)=CC=3)(O)C#C\C=C/C#C2)O[C@H](C)[C@@H](NO[C@@H]2O[C@H](C)[C@@H](SC(=O)C=3C(=C(OC)C(O[C@H]4[C@@H]([C@H](OC)[C@@H](O)[C@H](C)O4)O)=C(I)C=3C)OC)[C@@H](O)C2)[C@@H]1O HNMATTJJEPZZMM-BPKVFSPJSA-N 0.000 description 1
• 210000003079 salivary gland Anatomy 0.000 description 1
• 229960005399 satraplatin Drugs 0.000 description 1
• 190014017285 satraplatin Chemical compound 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
• 230000019491 signal transduction Effects 0.000 description 1
• 230000011664 signaling Effects 0.000 description 1
• XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
• 235000019345 sodium thiosulphate Nutrition 0.000 description 1
• AEQFSUDEHCCHBT-UHFFFAOYSA-M sodium valproate Chemical compound [Na+].CCCC(C([O-])=O)CCC AEQFSUDEHCCHBT-UHFFFAOYSA-M 0.000 description 1
• 229960003787 sorafenib Drugs 0.000 description 1
• 125000003003 spiro group Chemical group 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 235000011150 stannous chloride Nutrition 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 125000004426 substituted alkynyl group Chemical group 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 229940124530 sulfonamide Drugs 0.000 description 1
• 125000000565 sulfonamide group Chemical group 0.000 description 1
• 125000000542 sulfonic acid group Chemical group 0.000 description 1
• 239000011593 sulfur Chemical group 0.000 description 1
• 229960001796 sunitinib Drugs 0.000 description 1
• WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 230000002195 synergetic effect Effects 0.000 description 1
• 238000003786 synthesis reaction Methods 0.000 description 1
• 229920001059 synthetic polymer Polymers 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 229960001603 tamoxifen Drugs 0.000 description 1
• 238000002626 targeted therapy Methods 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• 238000003419 tautomerization reaction Methods 0.000 description 1
• RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
• SEXLALOUSMFTCE-ZIAGYGMSSA-N tert-butyl (1R,4R)-5-(4-amino-2-methylphenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound NC1=CC(=C(C=C1)N1[C@H]2CN([C@@H](C1)C2)C(=O)OC(C)(C)C)C SEXLALOUSMFTCE-ZIAGYGMSSA-N 0.000 description 1
• AEQRSNWEBJMXPJ-UONOGXRCSA-N tert-butyl (1R,4S)-5-(4-aminophenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound NC1=CC=C(C=C1)N1[C@@H]2CN([C@@H](C1)C2)C(=O)OC(C)(C)C AEQRSNWEBJMXPJ-UONOGXRCSA-N 0.000 description 1
• SBTKVNHCGNXKKN-STQMWFEESA-N tert-butyl (1S,4S)-5-(2-methoxy-4-nitrophenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound COC1=C(C=CC(=C1)[N+](=O)[O-])N1[C@@H]2CN([C@H](C1)C2)C(=O)OC(C)(C)C SBTKVNHCGNXKKN-STQMWFEESA-N 0.000 description 1
• BGEBIECWPPJYKF-KBPBESRZSA-N tert-butyl (1S,4S)-5-(2-methyl-4-nitrophenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound CC1=C(C=CC(=C1)[N+](=O)[O-])N1[C@@H]2CN([C@H](C1)C2)C(=O)OC(C)(C)C BGEBIECWPPJYKF-KBPBESRZSA-N 0.000 description 1
• UXAWXZDXVOYLII-HTQZYQBOSA-N tert-butyl (1r,4r)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C1[C@H]2N(C(=O)OC(C)(C)C)C[C@@H]1NC2 UXAWXZDXVOYLII-HTQZYQBOSA-N 0.000 description 1
• AEQRSNWEBJMXPJ-KBPBESRZSA-N tert-butyl (1s,4s)-5-(4-aminophenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C([C@]1(N(C[C@]2([H])C1)C(=O)OC(C)(C)C)[H])N2C1=CC=C(N)C=C1 AEQRSNWEBJMXPJ-KBPBESRZSA-N 0.000 description 1
• XKUXMTKVCYLKKE-OAHLLOKOSA-N tert-butyl (2R)-2-(methoxymethyl)-4-(4-nitrophenyl)piperazine-1-carboxylate Chemical compound COC[C@@H]1N(CCN(C1)C1=CC=C(C=C1)[N+](=O)[O-])C(=O)OC(C)(C)C XKUXMTKVCYLKKE-OAHLLOKOSA-N 0.000 description 1
• FFANQPGFOBBJTD-CYBMUJFWSA-N tert-butyl (2R)-4-(4-amino-2-ethoxycarbonylphenyl)-2-methylpiperazine-1-carboxylate Chemical compound NC1=CC(=C(C=C1)N1C[C@H](N(CC1)C(=O)OC(C)(C)C)C)C(=O)OCC FFANQPGFOBBJTD-CYBMUJFWSA-N 0.000 description 1
• PAFROFNNSHEYAO-LLVKDONJSA-N tert-butyl (2R)-4-(4-amino-3-fluorophenyl)-2-methylpiperazine-1-carboxylate Chemical compound NC1=C(C=C(C=C1)N1C[C@H](N(CC1)C(=O)OC(C)(C)C)C)F PAFROFNNSHEYAO-LLVKDONJSA-N 0.000 description 1
• PNVBSYLZLXGBJE-CQSZACIVSA-N tert-butyl (2R)-4-(4-aminophenyl)-2-(hydroxymethyl)piperazine-1-carboxylate Chemical compound NC1=CC=C(C=C1)N1C[C@@H](N(CC1)C(=O)OC(C)(C)C)CO PNVBSYLZLXGBJE-CQSZACIVSA-N 0.000 description 1
• BEMTXVFYBZDOGD-OAHLLOKOSA-N tert-butyl (2R)-4-[2-(hydroxymethyl)-4-nitrophenyl]-2-(methoxymethyl)piperazine-1-carboxylate Chemical compound OCC1=C(C=CC(=C1)[N+](=O)[O-])N1C[C@@H](N(CC1)C(=O)OC(C)(C)C)COC BEMTXVFYBZDOGD-OAHLLOKOSA-N 0.000 description 1
• FBNYPZCXVSQNIP-ZRKZCGFPSA-N tert-butyl (2R)-4-[4-amino-2-(2,2-difluoro-1-hydroxyethyl)phenyl]-2-methylpiperazine-1-carboxylate Chemical compound NC1=CC(=C(C=C1)N1C[C@H](N(CC1)C(=O)OC(C)(C)C)C)C(C(F)F)O FBNYPZCXVSQNIP-ZRKZCGFPSA-N 0.000 description 1
• HYOXRMFDBRKRDQ-CYBMUJFWSA-N tert-butyl (2R)-4-[4-amino-2-(2-hydroxypropan-2-yl)phenyl]-2-methylpiperazine-1-carboxylate Chemical compound NC1=CC(=C(C=C1)N1C[C@H](N(CC1)C(=O)OC(C)(C)C)C)C(C)(C)O HYOXRMFDBRKRDQ-CYBMUJFWSA-N 0.000 description 1
• UAASBZFCGKFEHO-LLVKDONJSA-N tert-butyl (2R)-4-[4-amino-2-(difluoromethoxy)phenyl]-2-methylpiperazine-1-carboxylate Chemical compound NC1=CC(=C(C=C1)N1C[C@H](N(CC1)C(=O)OC(C)(C)C)C)OC(F)F UAASBZFCGKFEHO-LLVKDONJSA-N 0.000 description 1
• DDMLXGWVBWQVOW-GFCCVEGCSA-N tert-butyl (2R)-4-[4-amino-2-(hydroxymethyl)phenyl]-2-methylpiperazine-1-carboxylate Chemical compound NC1=CC(=C(C=C1)N1C[C@H](N(CC1)C(=O)OC(C)(C)C)C)CO DDMLXGWVBWQVOW-GFCCVEGCSA-N 0.000 description 1
• MHOYZHJILBQLFT-CHWSQXEVSA-N tert-butyl (2R,5R)-4-(4-aminophenyl)-2,5-dimethylpiperazine-1-carboxylate Chemical compound NC1=CC=C(C=C1)N1C[C@H](N(C[C@H]1C)C(=O)OC(C)(C)C)C MHOYZHJILBQLFT-CHWSQXEVSA-N 0.000 description 1
• XKUXMTKVCYLKKE-HNNXBMFYSA-N tert-butyl (2S)-2-(methoxymethyl)-4-(4-nitrophenyl)piperazine-1-carboxylate Chemical compound COC[C@H]1N(CCN(C1)C1=CC=C(C=C1)[N+](=O)[O-])C(=O)OC(C)(C)C XKUXMTKVCYLKKE-HNNXBMFYSA-N 0.000 description 1
• PNVBSYLZLXGBJE-AWEZNQCLSA-N tert-butyl (2S)-4-(4-aminophenyl)-2-(hydroxymethyl)piperazine-1-carboxylate Chemical compound NC1=CC=C(C=C1)N1C[C@H](N(CC1)C(=O)OC(C)(C)C)CO PNVBSYLZLXGBJE-AWEZNQCLSA-N 0.000 description 1
• OXGNQZOUVOVRRD-HNNXBMFYSA-N tert-butyl (2S)-4-(4-aminophenyl)-2-(methoxymethyl)piperazine-1-carboxylate Chemical compound NC1=CC=C(C=C1)N1C[C@H](N(CC1)C(=O)OC(C)(C)C)COC OXGNQZOUVOVRRD-HNNXBMFYSA-N 0.000 description 1
• QZBZTZUNXLZYKU-LBPRGKRZSA-N tert-butyl (2S)-4-(4-aminophenyl)-2-methylpiperazine-1-carboxylate Chemical compound C[C@H]1CN(CCN1C(=O)OC(C)(C)C)c1ccc(N)cc1 QZBZTZUNXLZYKU-LBPRGKRZSA-N 0.000 description 1
• KETRKVONSKNJNH-OLZOCXBDSA-N tert-butyl (2S,5R)-2,5-dimethyl-4-(4-nitrophenyl)piperazine-1-carboxylate Chemical compound C[C@@H]1N(C[C@H](N(C1)C1=CC=C(C=C1)[N+](=O)[O-])C)C(=O)OC(C)(C)C KETRKVONSKNJNH-OLZOCXBDSA-N 0.000 description 1
• BCPPNDHZUPIXJM-MRVPVSSYSA-N tert-butyl (2r)-2-(hydroxymethyl)piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNC[C@@H]1CO BCPPNDHZUPIXJM-MRVPVSSYSA-N 0.000 description 1
• ODOJNXXZXCRBCC-SECBINFHSA-N tert-butyl (2r)-2-(methoxymethyl)piperazine-1-carboxylate Chemical compound COC[C@H]1CNCCN1C(=O)OC(C)(C)C ODOJNXXZXCRBCC-SECBINFHSA-N 0.000 description 1
• PGZCVLUQTJRRAA-RKDXNWHRSA-N tert-butyl (2r,5r)-2,5-dimethylpiperazine-1-carboxylate Chemical compound C[C@@H]1CN(C(=O)OC(C)(C)C)[C@H](C)CN1 PGZCVLUQTJRRAA-RKDXNWHRSA-N 0.000 description 1
• PGZCVLUQTJRRAA-DTWKUNHWSA-N tert-butyl (2r,5s)-2,5-dimethylpiperazine-1-carboxylate Chemical compound C[C@H]1CN(C(=O)OC(C)(C)C)[C@H](C)CN1 PGZCVLUQTJRRAA-DTWKUNHWSA-N 0.000 description 1
• BCPPNDHZUPIXJM-QMMMGPOBSA-N tert-butyl (2s)-2-(hydroxymethyl)piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNC[C@H]1CO BCPPNDHZUPIXJM-QMMMGPOBSA-N 0.000 description 1
• DATRVIMZZZVHMP-QMMMGPOBSA-N tert-butyl (2s)-2-methylpiperazine-1-carboxylate Chemical compound C[C@H]1CNCCN1C(=O)OC(C)(C)C DATRVIMZZZVHMP-QMMMGPOBSA-N 0.000 description 1
• BXFMCRUBXUJSJG-OAHLLOKOSA-N tert-butyl (3R)-3-(methoxymethyl)-4-(4-nitrophenyl)piperazine-1-carboxylate Chemical compound COC[C@H]1CN(CCN1C1=CC=C(C=C1)[N+](=O)[O-])C(=O)OC(C)(C)C BXFMCRUBXUJSJG-OAHLLOKOSA-N 0.000 description 1
• ATODYPMUYUNVSX-OAHLLOKOSA-N tert-butyl (3R)-4-(4-aminophenyl)-3-(methoxymethyl)piperazine-1-carboxylate Chemical compound NC1=CC=C(C=C1)N1[C@H](CN(CC1)C(=O)OC(C)(C)C)COC ATODYPMUYUNVSX-OAHLLOKOSA-N 0.000 description 1
• ATODYPMUYUNVSX-HNNXBMFYSA-N tert-butyl (3S)-4-(4-aminophenyl)-3-(methoxymethyl)piperazine-1-carboxylate Chemical compound NC1=CC=C(C=C1)N1[C@@H](CN(CC1)C(=O)OC(C)(C)C)COC ATODYPMUYUNVSX-HNNXBMFYSA-N 0.000 description 1
• NSILYQWHARROMG-MRVPVSSYSA-N tert-butyl (3r)-3-(hydroxymethyl)piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCN[C@@H](CO)C1 NSILYQWHARROMG-MRVPVSSYSA-N 0.000 description 1
• NSILYQWHARROMG-QMMMGPOBSA-N tert-butyl (3s)-3-(hydroxymethyl)piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCN[C@H](CO)C1 NSILYQWHARROMG-QMMMGPOBSA-N 0.000 description 1
• QIEBQSDOJMXWNN-UHFFFAOYSA-N tert-butyl 2,2-dimethylpiperazine-1-carboxylate;hydrochloride Chemical compound Cl.CC(C)(C)OC(=O)N1CCNCC1(C)C QIEBQSDOJMXWNN-UHFFFAOYSA-N 0.000 description 1
• KVOUHLVOTMOJBS-UHFFFAOYSA-N tert-butyl 2,6-diazaspiro[3.3]heptane-2-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC11CNC1 KVOUHLVOTMOJBS-UHFFFAOYSA-N 0.000 description 1
• SKZOKOOXLKHNFU-UHFFFAOYSA-N tert-butyl 2-(4-aminophenyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound C1C2CN(C(=O)OC(C)(C)C)CC2CN1C1=CC=C(N)C=C1 SKZOKOOXLKHNFU-UHFFFAOYSA-N 0.000 description 1
• VIBQTJLMJANION-UHFFFAOYSA-N tert-butyl 3,4-dihydro-2h-pyridine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC=C1 VIBQTJLMJANION-UHFFFAOYSA-N 0.000 description 1
• SQEHNYKAZJHZRI-UHFFFAOYSA-N tert-butyl 3-(4-aminophenyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound NC1=CC=C(C=C1)N1CC2CCC(C1)N2C(=O)OC(C)(C)C SQEHNYKAZJHZRI-UHFFFAOYSA-N 0.000 description 1
• QLFPHPJUIFSHRI-UHFFFAOYSA-N tert-butyl 3-(4-nitrophenyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound [N+](=O)([O-])C1=CC=C(C=C1)N1CC2CCC(C1)N2C(=O)OC(C)(C)C QLFPHPJUIFSHRI-UHFFFAOYSA-N 0.000 description 1
• NSFIPHYVHSGLLX-UHFFFAOYSA-N tert-butyl 3-[2-(hydroxymethyl)-4-nitrophenyl]-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound OCC1=C(C=CC(=C1)[N+](=O)[O-])N1CC2CCC(C1)N2C(=O)OC(C)(C)C NSFIPHYVHSGLLX-UHFFFAOYSA-N 0.000 description 1
• XXKCYKIJWLFVDG-UHFFFAOYSA-N tert-butyl 4,7-diazaspiro[2.5]octane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCNC11CC1 XXKCYKIJWLFVDG-UHFFFAOYSA-N 0.000 description 1
• SHQUZHHOMYZIGY-UHFFFAOYSA-N tert-butyl 4-(2-methoxy-4-nitrophenyl)piperazine-1-carboxylate Chemical compound COC1=CC([N+]([O-])=O)=CC=C1N1CCN(C(=O)OC(C)(C)C)CC1 SHQUZHHOMYZIGY-UHFFFAOYSA-N 0.000 description 1
• MATLRBKMCBPXPB-UHFFFAOYSA-N tert-butyl 4-(4-amino-2-cyanophenyl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=C(N)C=C1C#N MATLRBKMCBPXPB-UHFFFAOYSA-N 0.000 description 1
• IULXQAJBODFBAK-UHFFFAOYSA-N tert-butyl 4-(4-amino-2-fluorophenyl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=C(N)C=C1F IULXQAJBODFBAK-UHFFFAOYSA-N 0.000 description 1
• YAVMTFMZSXQHDC-UHFFFAOYSA-N tert-butyl 4-(4-amino-2-methoxyphenyl)piperazine-1-carboxylate Chemical compound COC1=CC(N)=CC=C1N1CCN(C(=O)OC(C)(C)C)CC1 YAVMTFMZSXQHDC-UHFFFAOYSA-N 0.000 description 1
• OLCJRLSBFJRSMZ-UHFFFAOYSA-N tert-butyl 4-(4-amino-2-methylphenyl)piperidine-1-carboxylate Chemical compound CC1=CC(N)=CC=C1C1CCN(C(=O)OC(C)(C)C)CC1 OLCJRLSBFJRSMZ-UHFFFAOYSA-N 0.000 description 1
• CNCSOOBVWRVUSB-UHFFFAOYSA-N tert-butyl 4-(4-aminophenyl)-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC(C=2C=CC(N)=CC=2)=C1 CNCSOOBVWRVUSB-UHFFFAOYSA-N 0.000 description 1
• ZTYRRWNDQSVOCL-UHFFFAOYSA-N tert-butyl 4-[(4-aminophenyl)methyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CC1=CC=C(N)C=C1 ZTYRRWNDQSVOCL-UHFFFAOYSA-N 0.000 description 1
• SYZMQLWCIYQQGI-UHFFFAOYSA-N tert-butyl 4-[4-amino-2-[(2,2,2-trifluoroethylamino)methyl]phenyl]piperazine-1-carboxylate Chemical compound NC1=CC(=C(C=C1)N1CCN(CC1)C(=O)OC(C)(C)C)CNCC(F)(F)F SYZMQLWCIYQQGI-UHFFFAOYSA-N 0.000 description 1
• ATKXYMFOJSCWGN-UHFFFAOYSA-N tert-butyl 4-[4-nitro-2-[(2,2,2-trifluoroethylamino)methyl]phenyl]piperazine-1-carboxylate Chemical compound [N+](=O)([O-])C1=CC(=C(C=C1)N1CCN(CC1)C(=O)OC(C)(C)C)CNCC(F)(F)F ATKXYMFOJSCWGN-UHFFFAOYSA-N 0.000 description 1
• LVBIUFMRSWDCPR-UHFFFAOYSA-N tert-butyl 4-amino-12-azatricyclo[7.2.1.02,7]dodeca-2(7),3,5-triene-12-carboxylate Chemical compound NC1=CC2=C(CC3CCC2N3C(=O)OC(C)(C)C)C=C1 LVBIUFMRSWDCPR-UHFFFAOYSA-N 0.000 description 1
• PWQLFIKTGRINFF-UHFFFAOYSA-N tert-butyl 4-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(O)CC1 PWQLFIKTGRINFF-UHFFFAOYSA-N 0.000 description 1
• ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
• AEQRSNWEBJMXPJ-UHFFFAOYSA-N tert-butyl 5-(4-aminophenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC2CC1CN2C1=CC=C(N)C=C1 AEQRSNWEBJMXPJ-UHFFFAOYSA-N 0.000 description 1
• OSTHJJCOQGHBRD-UHFFFAOYSA-N tert-butyl 6-(4-aminophenyl)-2,6-diazaspiro[3.3]heptane-2-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC21CN(C=1C=CC(N)=CC=1)C2 OSTHJJCOQGHBRD-UHFFFAOYSA-N 0.000 description 1
• BUVHPVNCRLELIM-UHFFFAOYSA-N tert-butyl 7-(4-aminophenyl)-3-oxa-7,9-diazabicyclo[3.3.1]nonane-9-carboxylate Chemical compound NC1=CC=C(C=C1)N1CC2COCC(C1)N2C(=O)OC(C)(C)C BUVHPVNCRLELIM-UHFFFAOYSA-N 0.000 description 1
• MGEJCOJYQNUMTR-UHFFFAOYSA-N tert-butyl 7-(4-aminophenyl)-4,7-diazaspiro[2.5]octane-4-carboxylate Chemical compound NC1=CC=C(C=C1)N1CCN(C2(CC2)C1)C(=O)OC(C)(C)C MGEJCOJYQNUMTR-UHFFFAOYSA-N 0.000 description 1
• GFRLCPBMTQVIPB-UHFFFAOYSA-N tert-butyl 7-(4-nitrophenyl)-3-oxa-7,9-diazabicyclo[3.3.1]nonane-9-carboxylate Chemical compound [N+](=O)([O-])C1=CC=C(C=C1)N1CC2COCC(C1)N2C(=O)OC(C)(C)C GFRLCPBMTQVIPB-UHFFFAOYSA-N 0.000 description 1
• KNLHAHSBNOMFSN-UHFFFAOYSA-N tert-butyl N-[[2-(4-acetylpiperazin-1-yl)-5-nitrophenyl]methyl]-N-methylcarbamate Chemical compound C(C)(=O)N1CCN(CC1)C1=C(CN(C(OC(C)(C)C)=O)C)C=C(C=C1)[N+](=O)[O-] KNLHAHSBNOMFSN-UHFFFAOYSA-N 0.000 description 1
• DZRWMPXYEACDFK-UHFFFAOYSA-N tert-butyl N-methyl-N-[(5-nitro-2-piperidin-1-ylphenyl)methyl]carbamate Chemical compound CN(C(OC(C)(C)C)=O)CC1=C(C=CC(=C1)[N+](=O)[O-])N1CCCCC1 DZRWMPXYEACDFK-UHFFFAOYSA-N 0.000 description 1
• DFOKAUYLSGBBID-UHFFFAOYSA-N tert-butyl N-methyl-N-[(5-nitro-2-pyrrolidin-1-ylphenyl)methyl]carbamate Chemical compound CN(C(OC(C)(C)C)=O)CC1=C(C=CC(=C1)[N+](=O)[O-])N1CCCC1 DFOKAUYLSGBBID-UHFFFAOYSA-N 0.000 description 1
• IZUZIVIUDTZPFE-UHFFFAOYSA-N tert-butyl decanoate Chemical compound CCCCCCCCCC(=O)OC(C)(C)C IZUZIVIUDTZPFE-UHFFFAOYSA-N 0.000 description 1
• SOYSJYBVYFILEK-UHFFFAOYSA-N tert-butyl n-[1-(4-aminophenyl)cyclobutyl]carbamate Chemical compound C=1C=C(N)C=CC=1C1(NC(=O)OC(C)(C)C)CCC1 SOYSJYBVYFILEK-UHFFFAOYSA-N 0.000 description 1
• JRLPTDRBGXGBKE-UHFFFAOYSA-N tert-butyl n-[2-(4-aminophenoxy)ethyl]-n-methylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)CCOC1=CC=C(N)C=C1 JRLPTDRBGXGBKE-UHFFFAOYSA-N 0.000 description 1
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 230000002381 testicular Effects 0.000 description 1
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
• CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical class CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
• 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
• 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
• 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
• QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
• CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 125000001984 thiazolidinyl group Chemical group 0.000 description 1
• 125000002769 thiazolinyl group Chemical group 0.000 description 1
• 125000005032 thiofuranyl group Chemical group S1C(=CC=C1)* 0.000 description 1
• 229960001196 thiotepa Drugs 0.000 description 1
• 210000001685 thyroid gland Anatomy 0.000 description 1
• AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
• 229960003087 tioguanine Drugs 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 229960005267 tositumomab Drugs 0.000 description 1
• 229960000575 trastuzumab Drugs 0.000 description 1
• 230000016596 traversing start control point of mitotic cell cycle Effects 0.000 description 1
• 238000011277 treatment modality Methods 0.000 description 1
• 125000004306 triazinyl 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
• NQMRYBIKMRVZLB-NIIDSAIPSA-N trideuteriomethanamine;hydrochloride Chemical compound Cl.[2H]C([2H])([2H])N NQMRYBIKMRVZLB-NIIDSAIPSA-N 0.000 description 1
• 230000001960 triggered effect Effects 0.000 description 1
• 229910052722 tritium Inorganic materials 0.000 description 1
• 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
• 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
• 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
• 238000000825 ultraviolet detection Methods 0.000 description 1
• 210000003708 urethra Anatomy 0.000 description 1
• 210000003932 urinary bladder Anatomy 0.000 description 1
• 210000004291 uterus Anatomy 0.000 description 1
• 238000003828 vacuum filtration Methods 0.000 description 1
• 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 229940102566 valproate Drugs 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 229960003048 vinblastine Drugs 0.000 description 1
• JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
• OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
• 229960004528 vincristine Drugs 0.000 description 1
• OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
• GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
• 229960002066 vinorelbine Drugs 0.000 description 1
• 229920002554 vinyl polymer Polymers 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 229940100445 wheat starch Drugs 0.000 description 1