JP5889875B2 - アザインダゾール - Google Patents

Info

Publication number

JP5889875B2

JP5889875B2 JP2013509262A JP2013509262A JP5889875B2 JP 5889875 B2 JP5889875 B2 JP 5889875B2 JP 2013509262 A JP2013509262 A JP 2013509262A JP 2013509262 A JP2013509262 A JP 2013509262A JP 5889875 B2 JP5889875 B2 JP 5889875B2

Authority

JP

Japan

Prior art keywords

methyl

pyridinyl

oxo

dihydro

pyridine

Prior art date

2010-05-07

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Expired - Fee Related

Links

• Espacenet
• Global Dossier
• Discuss

• QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims description 234
• -1 amino, hydroxyl Chemical group 0.000 claims description 181
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 130
• 229910052757 nitrogen Inorganic materials 0.000 claims description 78
• 206010028980 Neoplasm Diseases 0.000 claims description 62
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 58
• 125000001072 heteroaryl group Chemical group 0.000 claims description 52
• FABMZTHRDOHPDN-UHFFFAOYSA-N 6-chloro-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=C(Cl)N=C2N(C(C)C)N=CC2=C1C(=O)NCC1=C(C)C=C(C)NC1=O FABMZTHRDOHPDN-UHFFFAOYSA-N 0.000 claims description 49
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 47
• 125000003118 aryl group Chemical group 0.000 claims description 46
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 44
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 42
• 201000011510 cancer Diseases 0.000 claims description 42
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 41
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 40
• VFQXVTODMYMSMJ-UHFFFAOYSA-N isonicotinamide Chemical compound NC(=O)C1=CC=NC=C1 VFQXVTODMYMSMJ-UHFFFAOYSA-N 0.000 claims description 33
• 229910052739 hydrogen Inorganic materials 0.000 claims description 30
• 239000001257 hydrogen Substances 0.000 claims description 28
• 125000000217 alkyl group Chemical group 0.000 claims description 27
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 26
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 26
• 125000000081 (C5-C8) cycloalkenyl group Chemical group 0.000 claims description 24
• 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 20
• 239000008194 pharmaceutical composition Substances 0.000 claims description 20
• 150000003839 salts Chemical class 0.000 claims description 20
• 229910052760 oxygen Inorganic materials 0.000 claims description 19
• 229920006395 saturated elastomer Polymers 0.000 claims description 19
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 18
• 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 16
• 150000001602 bicycloalkyls Chemical group 0.000 claims description 16
• 206010025323 Lymphomas Diseases 0.000 claims description 14
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 12
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 12
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
• 150000002431 hydrogen Chemical class 0.000 claims description 12
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 8
• 125000003282 alkyl amino group Chemical group 0.000 claims description 8
• 229910052799 carbon Inorganic materials 0.000 claims description 8
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
• 229910052717 sulfur Chemical group 0.000 claims description 8
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 7
• 239000001301 oxygen Substances 0.000 claims description 7
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
• 206010006187 Breast cancer Diseases 0.000 claims description 6
• 206010033128 Ovarian cancer Diseases 0.000 claims description 6
• 206010061535 Ovarian neoplasm Diseases 0.000 claims description 6
• 201000010099 disease Diseases 0.000 claims description 6
• 125000005842 heteroatom Chemical group 0.000 claims description 6
• VKSDJJINVLWPPN-UHFFFAOYSA-N 1-tert-butyl-6-chloro-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-3-methylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C=12C(C)=NN(C(C)(C)C)C2=NC(Cl)=CC=1C(=O)NCC1=C(C)C=C(C)NC1=O VKSDJJINVLWPPN-UHFFFAOYSA-N 0.000 claims description 5
• 208000026310 Breast neoplasm Diseases 0.000 claims description 5
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 5
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
• 201000009410 rhabdomyosarcoma Diseases 0.000 claims description 5
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 4
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
• 208000008383 Wilms tumor Diseases 0.000 claims description 4
• KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims description 4
• 125000004122 cyclic group Chemical group 0.000 claims description 4
• 208000005017 glioblastoma Diseases 0.000 claims description 4
• 208000032839 leukemia Diseases 0.000 claims description 4
• SNICLKHAPMIQAK-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C(C=N1)=CC=C1N1CCN(C)CC1 SNICLKHAPMIQAK-UHFFFAOYSA-N 0.000 claims description 4
• 125000004043 oxo group Chemical group O=* 0.000 claims description 4
• 239000011593 sulfur Chemical group 0.000 claims description 4
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 3
• 201000001441 melanoma Diseases 0.000 claims description 3
• LVQZSFQDGDBHJW-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-yl-6-(2-pyridin-4-ylethynyl)pyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C#CC1=CC=NC=C1 LVQZSFQDGDBHJW-UHFFFAOYSA-N 0.000 claims description 3
• 201000008026 nephroblastoma Diseases 0.000 claims description 3
• 201000008968 osteosarcoma Diseases 0.000 claims description 3
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
• FTRNTBOWPSRAEH-UHFFFAOYSA-N 1-benzyl-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-methylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C=12C=NN(CC=3C=CC=CC=3)C2=NC(C)=CC=1C(=O)NCC1=C(C)C=C(C)NC1=O FTRNTBOWPSRAEH-UHFFFAOYSA-N 0.000 claims description 2
• IIDGHJNVOYHFLT-UHFFFAOYSA-N 1-cyclobutyl-6-cyclopropyl-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-3-methylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C12=NC(C3CC3)=CC(C(=O)NCC=3C(NC(C)=CC=3C)=O)=C2C(C)=NN1C1CCC1 IIDGHJNVOYHFLT-UHFFFAOYSA-N 0.000 claims description 2
• ZVWGPMUZNXVNEB-UHFFFAOYSA-N 1-cyclohexyl-6-cyclopropyl-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-3-methylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C12=NC(C3CC3)=CC(C(=O)NCC=3C(NC(C)=CC=3C)=O)=C2C(C)=NN1C1CCCCC1 ZVWGPMUZNXVNEB-UHFFFAOYSA-N 0.000 claims description 2
• BCXVOWWRYJQHNM-UHFFFAOYSA-N 1-cyclopentyl-6-cyclopropyl-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-3-methylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C12=NC(C3CC3)=CC(C(=O)NCC=3C(NC(C)=CC=3C)=O)=C2C(C)=NN1C1CCCC1 BCXVOWWRYJQHNM-UHFFFAOYSA-N 0.000 claims description 2
• VUJVCWWIQRDSNQ-UHFFFAOYSA-N 1-tert-butyl-6-cyclopropyl-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-3-methylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C=12C(C)=NN(C(C)(C)C)C2=NC(C2CC2)=CC=1C(=O)NCC1=C(C)C=C(C)NC1=O VUJVCWWIQRDSNQ-UHFFFAOYSA-N 0.000 claims description 2
• GBNAZZHFAWCZDP-UHFFFAOYSA-N 1-tert-butyl-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-3-methyl-6-(2-oxo-1,3-dihydrobenzimidazol-5-yl)pyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C=12C(C)=NN(C(C)(C)C)C2=NC(C=2C=C3NC(=O)NC3=CC=2)=CC=1C(=O)NCC1=C(C)C=C(C)NC1=O GBNAZZHFAWCZDP-UHFFFAOYSA-N 0.000 claims description 2
• KFGLSNDZHPVZLB-UHFFFAOYSA-N 1-tert-butyl-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-3-methyl-6-(6-morpholin-4-ylpyridin-3-yl)pyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C=12C(C)=NN(C(C)(C)C)C2=NC(C=2C=NC(=CC=2)N2CCOCC2)=CC=1C(=O)NCC1=C(C)C=C(C)NC1=O KFGLSNDZHPVZLB-UHFFFAOYSA-N 0.000 claims description 2
• MNFXCZXHQVNDKD-UHFFFAOYSA-N 1-tert-butyl-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-3-methyl-6-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]pyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1CN(C)CCN1C1=CC=C(C=2N=C3N(N=C(C)C3=C(C(=O)NCC=3C(NC(C)=CC=3C)=O)C=2)C(C)(C)C)C=N1 MNFXCZXHQVNDKD-UHFFFAOYSA-N 0.000 claims description 2
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
• LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 claims description 2
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
• ZYGCNKBZFDOZPV-UHFFFAOYSA-N 6-(2,1,3-benzoxadiazol-5-yl)-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-3-methyl-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=C(C2=CC3=NON=C3C=C2)N=C2N(C(C)C)N=C(C)C2=C1C(=O)NCC1=C(C)C=C(C)NC1=O ZYGCNKBZFDOZPV-UHFFFAOYSA-N 0.000 claims description 2
• ROUZJNZVOLGBLI-UHFFFAOYSA-N 6-(2-aminopyridin-4-yl)-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C1=CC=NC(N)=C1 ROUZJNZVOLGBLI-UHFFFAOYSA-N 0.000 claims description 2
• JNXHLGFBCMVYNR-UHFFFAOYSA-N 6-(2-aminopyrimidin-5-yl)-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C1=CN=C(N)N=C1 JNXHLGFBCMVYNR-UHFFFAOYSA-N 0.000 claims description 2
• SWIDHBXIQYEALH-UHFFFAOYSA-N 6-(2-aminoquinazolin-6-yl)-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-3-methyl-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=C(C=2C=C3C=NC(N)=NC3=CC=2)N=C2N(C(C)C)N=C(C)C2=C1C(=O)NCC1=C(C)C=C(C)NC1=O SWIDHBXIQYEALH-UHFFFAOYSA-N 0.000 claims description 2
• BBSASWROZCPDRJ-UHFFFAOYSA-N 6-(2h-benzotriazol-5-yl)-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=C(C=2C=C3N=NNC3=CC=2)N=C2N(C(C)C)N=CC2=C1C(=O)NCC1=C(C)C=C(C)NC1=O BBSASWROZCPDRJ-UHFFFAOYSA-N 0.000 claims description 2
• PYZYAPPUGKUPEE-UHFFFAOYSA-N 6-(3-acetamidophenyl)-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C1=CC=CC(NC(C)=O)=C1 PYZYAPPUGKUPEE-UHFFFAOYSA-N 0.000 claims description 2
• CYKQSUGLXKUFHX-UHFFFAOYSA-N 6-(3-aminophenyl)-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C1=CC=CC(N)=C1 CYKQSUGLXKUFHX-UHFFFAOYSA-N 0.000 claims description 2
• GQCKGKFHRBAKCN-UHFFFAOYSA-N 6-(4-acetamidophenyl)-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C1=CC=C(NC(C)=O)C=C1 GQCKGKFHRBAKCN-UHFFFAOYSA-N 0.000 claims description 2
• SPDITUWEEYOCJY-UHFFFAOYSA-N 6-(4-acetamidophenyl)-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-3-methyl-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=C(C)C2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C1=CC=C(NC(C)=O)C=C1 SPDITUWEEYOCJY-UHFFFAOYSA-N 0.000 claims description 2
• NCTMOSCJBLHHAG-UHFFFAOYSA-N 6-(4-aminophenyl)-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C1=CC=C(N)C=C1 NCTMOSCJBLHHAG-UHFFFAOYSA-N 0.000 claims description 2
• KWPKXQFYRMVTLS-UHFFFAOYSA-N 6-(4-carbamoylanilino)-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1NC1=CC=C(C(N)=O)C=C1 KWPKXQFYRMVTLS-UHFFFAOYSA-N 0.000 claims description 2
• QZGYRKOMVWBKSE-UHFFFAOYSA-N 6-(4-carbamoylphenyl)-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C1=CC=C(C(N)=O)C=C1 QZGYRKOMVWBKSE-UHFFFAOYSA-N 0.000 claims description 2
• LPCJTPOYPJHJRS-UHFFFAOYSA-N 6-(6-acetamidopyridin-3-yl)-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C1=CC=C(NC(C)=O)N=C1 LPCJTPOYPJHJRS-UHFFFAOYSA-N 0.000 claims description 2
• QMMFSKNFVSSDEK-UHFFFAOYSA-N 6-(6-aminopyridin-3-yl)-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C1=CC=C(N)N=C1 QMMFSKNFVSSDEK-UHFFFAOYSA-N 0.000 claims description 2
• PYPWLVFEJOOVDR-UHFFFAOYSA-N 6-[2-(dimethylamino)ethylamino]-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=C(NCCN(C)C)N=C2N(C(C)C)N=CC2=C1C(=O)NCC1=C(C)C=C(C)NC1=O PYPWLVFEJOOVDR-UHFFFAOYSA-N 0.000 claims description 2
• ROLJNRNHZVGSDA-UHFFFAOYSA-N 6-[5-(benzenesulfonamido)pyridin-3-yl]-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C(C=1)=CN=CC=1NS(=O)(=O)C1=CC=CC=C1 ROLJNRNHZVGSDA-UHFFFAOYSA-N 0.000 claims description 2
• OPKVDCHRFVMHAG-UHFFFAOYSA-N 6-[5-(cyclopropylsulfonylamino)-6-methoxypyridin-3-yl]-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound COC1=NC=C(C=2N=C3N(C(C)C)N=CC3=C(C(=O)NCC=3C(NC(C)=CC=3C)=O)C=2)C=C1NS(=O)(=O)C1CC1 OPKVDCHRFVMHAG-UHFFFAOYSA-N 0.000 claims description 2
• VZGZROHQXCXVNG-UHFFFAOYSA-N 6-[6-(dimethylamino)pyridin-3-yl]-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C1=CC=C(N(C)C)N=C1 VZGZROHQXCXVNG-UHFFFAOYSA-N 0.000 claims description 2
• SEKDNVJKSGMKBR-UHFFFAOYSA-N 6-amino-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=C(N)N=C2N(C(C)C)N=CC2=C1C(=O)NCC1=C(C)C=C(C)NC1=O SEKDNVJKSGMKBR-UHFFFAOYSA-N 0.000 claims description 2
• ZJBQVJXGTZEWCX-UHFFFAOYSA-N 6-anilino-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1NC1=CC=CC=C1 ZJBQVJXGTZEWCX-UHFFFAOYSA-N 0.000 claims description 2
• SWHWPZPVKCRCLG-UHFFFAOYSA-N 6-cyclopropyl-1-(1-cyclopropylethyl)-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-3-methylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C(C)C2=C(C(=O)NCC=3C(NC(C)=CC=3C)=O)C=C(C3CC3)N=C2N1C(C)C1CC1 SWHWPZPVKCRCLG-UHFFFAOYSA-N 0.000 claims description 2
• RQNMLYXYHKMXAV-UHFFFAOYSA-N 6-cyclopropyl-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-[2-(methanesulfonamido)ethyl]pyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound O=C1NC(C)=CC(C)=C1CNC(=O)C1=CC(C2CC2)=NC2=C1C=NN2CCNS(C)(=O)=O RQNMLYXYHKMXAV-UHFFFAOYSA-N 0.000 claims description 2
• NAGLYMIXBUFMJR-UHFFFAOYSA-N 6-cyclopropyl-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-ethylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(CC)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C1CC1 NAGLYMIXBUFMJR-UHFFFAOYSA-N 0.000 claims description 2
• CKWGNYPWTNPJTL-UHFFFAOYSA-N 6-cyclopropyl-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(CCC)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C1CC1 CKWGNYPWTNPJTL-UHFFFAOYSA-N 0.000 claims description 2
• ONAZPLZAUCSZBY-UHFFFAOYSA-N 6-cyclopropyl-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-pyridin-4-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound O=C1NC(C)=CC(C)=C1CNC(=O)C1=CC(C2CC2)=NC2=C1C=NN2C1=CC=NC=C1 ONAZPLZAUCSZBY-UHFFFAOYSA-N 0.000 claims description 2
• PKSJPYKWNYLLFG-UHFFFAOYSA-N 6-cyclopropyl-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-3-methyl-1-(1-methylpiperidin-4-yl)pyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1CN(C)CCC1N1C2=NC(C3CC3)=CC(C(=O)NCC=3C(NC(C)=CC=3C)=O)=C2C(C)=N1 PKSJPYKWNYLLFG-UHFFFAOYSA-N 0.000 claims description 2
• CDIJNQNSRQUHHH-UHFFFAOYSA-N 6-cyclopropyl-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-3-methyl-1-(oxan-4-yl)pyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C12=NC(C3CC3)=CC(C(=O)NCC=3C(NC(C)=CC=3C)=O)=C2C(C)=NN1C1CCOCC1 CDIJNQNSRQUHHH-UHFFFAOYSA-N 0.000 claims description 2
• IYHWHTORRRTBJP-UHFFFAOYSA-N 6-cyclopropyl-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-3-methyl-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=C(C)C2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C1CC1 IYHWHTORRRTBJP-UHFFFAOYSA-N 0.000 claims description 2
• AWMFEVJSBRGMKX-UHFFFAOYSA-N 6-cyclopropyl-n-[(4-methyl-2-oxo-6-propyl-1h-pyridin-3-yl)methyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound O=C1NC(CCC)=CC(C)=C1CNC(=O)C1=CC(C2CC2)=NC2=C1C=NN2C(C)C AWMFEVJSBRGMKX-UHFFFAOYSA-N 0.000 claims description 2
• GDDSMOUZBSWFPX-UHFFFAOYSA-N 6-cyclopropyl-n-[(6-methyl-2-oxo-4-phenyl-1h-pyridin-3-yl)methyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C=2C=CC=CC=2)=O)C=C1C1CC1 GDDSMOUZBSWFPX-UHFFFAOYSA-N 0.000 claims description 2
• YBGKRLSRBCWQEQ-UHFFFAOYSA-N 6-cyclopropyl-n-[(6-methyl-2-oxo-4-propan-2-yl-1h-pyridin-3-yl)methyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=C(C)NC(=O)C(CNC(=O)C=2C=3C=NN(C=3N=C(C=2)C2CC2)C(C)C)=C1C(C)C YBGKRLSRBCWQEQ-UHFFFAOYSA-N 0.000 claims description 2
• FSDXIBKXOHYNOA-UHFFFAOYSA-N 6-cyclopropyl-n-[(6-methyl-2-oxo-4-propyl-1h-pyridin-3-yl)methyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=C(C)NC(=O)C(CNC(=O)C=2C=3C=NN(C=3N=C(C=2)C2CC2)C(C)C)=C1CCC FSDXIBKXOHYNOA-UHFFFAOYSA-N 0.000 claims description 2
• DHKHLSCPKJCJNP-UHFFFAOYSA-N 6-cyclopropyl-n-[[6-methyl-2-oxo-4-(trifluoromethyl)-1h-pyridin-3-yl]methyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C(F)(F)F)=O)C=C1C1CC1 DHKHLSCPKJCJNP-UHFFFAOYSA-N 0.000 claims description 2
• 206010005003 Bladder cancer Diseases 0.000 claims description 2
• 208000003174 Brain Neoplasms Diseases 0.000 claims description 2
• 206010014967 Ependymoma Diseases 0.000 claims description 2
• 208000006168 Ewing Sarcoma Diseases 0.000 claims description 2
• 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
• 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical group C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 2
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 2
• UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims description 2
• 201000010536 head and neck cancer Diseases 0.000 claims description 2
• 208000014829 head and neck neoplasm Diseases 0.000 claims description 2
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
• 201000007270 liver cancer Diseases 0.000 claims description 2
• 208000014018 liver neoplasm Diseases 0.000 claims description 2
• 201000005202 lung cancer Diseases 0.000 claims description 2
• 208000020816 lung neoplasm Diseases 0.000 claims description 2
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
• RVPHJHONMNAGSK-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1,6-di(propan-2-yl)pyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C=12C=NN(C(C)C)C2=NC(C(C)C)=CC=1C(=O)NCC1=C(C)C=C(C)NC1=O RVPHJHONMNAGSK-UHFFFAOYSA-N 0.000 claims description 2
• IWIDAPBNWDDLAR-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-yl-6-(4-sulfamoylphenyl)pyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C1=CC=C(S(N)(=O)=O)C=C1 IWIDAPBNWDDLAR-UHFFFAOYSA-N 0.000 claims description 2
• MMDJLTWESKNNRE-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-yl-6-(prop-2-enylamino)pyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=C(NCC=C)N=C2N(C(C)C)N=CC2=C1C(=O)NCC1=C(C)C=C(C)NC1=O MMDJLTWESKNNRE-UHFFFAOYSA-N 0.000 claims description 2
• GQEAQQLZXOTRPN-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=CN=C2N(C(C)C)N=CC2=C1C(=O)NCC1=C(C)C=C(C)NC1=O GQEAQQLZXOTRPN-UHFFFAOYSA-N 0.000 claims description 2
• MAMZJJPZEPIRKX-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-3-methyl-6-(2-oxo-1,3-dihydrobenzimidazol-5-yl)-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=C(C=2C=C3NC(=O)NC3=CC=2)N=C2N(C(C)C)N=C(C)C2=C1C(=O)NCC1=C(C)C=C(C)NC1=O MAMZJJPZEPIRKX-UHFFFAOYSA-N 0.000 claims description 2
• HHFDOLJYRZAQEN-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-3-methyl-6-(6-morpholin-4-ylpyridin-3-yl)-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=C(C)C2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C(C=N1)=CC=C1N1CCOCC1 HHFDOLJYRZAQEN-UHFFFAOYSA-N 0.000 claims description 2
• DYBCKEUECIXCMR-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-3-methyl-6-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=C(C)C2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C(C=N1)=CC=C1N1CCN(C)CC1 DYBCKEUECIXCMR-UHFFFAOYSA-N 0.000 claims description 2
• HXLVZOZISHVQAP-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-(1h-indazol-5-yl)-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=C(C=2C=C3C=NNC3=CC=2)N=C2N(C(C)C)N=CC2=C1C(=O)NCC1=C(C)C=C(C)NC1=O HXLVZOZISHVQAP-UHFFFAOYSA-N 0.000 claims description 2
• DPOKPPDUEUFLKK-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-(1h-indazol-6-yl)-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=C(C=2C=C3NN=CC3=CC=2)N=C2N(C(C)C)N=CC2=C1C(=O)NCC1=C(C)C=C(C)NC1=O DPOKPPDUEUFLKK-UHFFFAOYSA-N 0.000 claims description 2
• CRYXKQPGUZMKLK-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-(2-hydroxyethylamino)-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=C(NCCO)N=C2N(C(C)C)N=CC2=C1C(=O)NCC1=C(C)C=C(C)NC1=O CRYXKQPGUZMKLK-UHFFFAOYSA-N 0.000 claims description 2
• FENLBPIFXYKGLZ-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-(2-methoxypyridin-4-yl)-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=NC(OC)=CC(C=2N=C3N(C(C)C)N=CC3=C(C(=O)NCC=3C(NC(C)=CC=3C)=O)C=2)=C1 FENLBPIFXYKGLZ-UHFFFAOYSA-N 0.000 claims description 2
• LXJKHNJMAHAASA-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-(2-methylphenyl)-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C1=CC=CC=C1C LXJKHNJMAHAASA-UHFFFAOYSA-N 0.000 claims description 2
• AVQKYORNLOKWBI-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-(2-morpholin-4-ylpyridin-4-yl)-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C(C=1)=CC=NC=1N1CCOCC1 AVQKYORNLOKWBI-UHFFFAOYSA-N 0.000 claims description 2
• DHDAGJRZBJHQQW-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-(2-oxo-1,3-dihydrobenzimidazol-5-yl)-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=C(C=2C=C3NC(=O)NC3=CC=2)N=C2N(C(C)C)N=CC2=C1C(=O)NCC1=C(C)C=C(C)NC1=O DHDAGJRZBJHQQW-UHFFFAOYSA-N 0.000 claims description 2
• KXXLCLVJGUVBTJ-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-(2-oxo-1,3-dihydroindol-5-yl)-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=C(C=2C=C3CC(=O)NC3=CC=2)N=C2N(C(C)C)N=CC2=C1C(=O)NCC1=C(C)C=C(C)NC1=O KXXLCLVJGUVBTJ-UHFFFAOYSA-N 0.000 claims description 2
• VJRHUHGJWWANDO-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-(2-oxo-1,3-dihydroindol-6-yl)-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=C(C=2C=C3NC(=O)CC3=CC=2)N=C2N(C(C)C)N=CC2=C1C(=O)NCC1=C(C)C=C(C)NC1=O VJRHUHGJWWANDO-UHFFFAOYSA-N 0.000 claims description 2
• YWNPYDHFOXXNNH-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-(2-phenylethyl)-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1CCC1=CC=CC=C1 YWNPYDHFOXXNNH-UHFFFAOYSA-N 0.000 claims description 2
• WCUROQOMQQPYKI-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-(2-phenylethynyl)-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C#CC1=CC=CC=C1 WCUROQOMQQPYKI-UHFFFAOYSA-N 0.000 claims description 2
• FSUVZKXRKBJLHO-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-(3-hydroxy-3-methylbut-1-ynyl)-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=C(C#CC(C)(C)O)N=C2N(C(C)C)N=CC2=C1C(=O)NCC1=C(C)C=C(C)NC1=O FSUVZKXRKBJLHO-UHFFFAOYSA-N 0.000 claims description 2
• ZFTBTZYCUSUGSY-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-(3-methyl-2h-indazol-5-yl)-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=C(C=2C=C3C(C)=NNC3=CC=2)N=C2N(C(C)C)N=CC2=C1C(=O)NCC1=C(C)C=C(C)NC1=O ZFTBTZYCUSUGSY-UHFFFAOYSA-N 0.000 claims description 2
• YBAJUXLZNKTGDL-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-(4-fluorophenyl)-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C1=CC=C(F)C=C1 YBAJUXLZNKTGDL-UHFFFAOYSA-N 0.000 claims description 2
• KFMVMEOFGDXIJR-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-(5-methoxypyridin-3-yl)-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound COC1=CN=CC(C=2N=C3N(C(C)C)N=CC3=C(C(=O)NCC=3C(NC(C)=CC=3C)=O)C=2)=C1 KFMVMEOFGDXIJR-UHFFFAOYSA-N 0.000 claims description 2
• KMQGNFBUFRVFNI-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-(5-methylsulfonylpyridin-3-yl)-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C1=CN=CC(S(C)(=O)=O)=C1 KMQGNFBUFRVFNI-UHFFFAOYSA-N 0.000 claims description 2
• STTDFESLIVVLKE-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-(6-methoxypyridin-3-yl)-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=NC(OC)=CC=C1C1=CC(C(=O)NCC=2C(NC(C)=CC=2C)=O)=C(C=NN2C(C)C)C2=N1 STTDFESLIVVLKE-UHFFFAOYSA-N 0.000 claims description 2
• OBASFAPNSSLYMR-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-(6-morpholin-4-ylpyridin-3-yl)-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C(C=N1)=CC=C1N1CCOCC1 OBASFAPNSSLYMR-UHFFFAOYSA-N 0.000 claims description 2
• JRHSMAGHHVRSNA-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-(7-oxo-6,8-dihydro-5h-1,8-naphthyridin-3-yl)-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=C(C=2C=C3CCC(=O)N=C3NC=2)N=C2N(C(C)C)N=CC2=C1C(=O)NCC1=C(C)C=C(C)NC1=O JRHSMAGHHVRSNA-UHFFFAOYSA-N 0.000 claims description 2
• TVEDDGSQQZGNAT-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-(ethylamino)-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C=12C=NN(C(C)C)C2=NC(NCC)=CC=1C(=O)NCC1=C(C)C=C(C)NC1=O TVEDDGSQQZGNAT-UHFFFAOYSA-N 0.000 claims description 2
• FJMKUHGWRIGUAK-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-(oxan-4-ylamino)-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1NC1CCOCC1 FJMKUHGWRIGUAK-UHFFFAOYSA-N 0.000 claims description 2
• KHDOEYMZHHRWEA-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-(piperidin-4-ylamino)-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1NC1CCNCC1 KHDOEYMZHHRWEA-UHFFFAOYSA-N 0.000 claims description 2
• CZQGOIXSJFKZPT-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-[(2-oxo-1,3-dihydrobenzimidazol-5-yl)amino]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=C(NC=2C=C3NC(=O)NC3=CC=2)N=C2N(C(C)C)N=CC2=C1C(=O)NCC1=C(C)C=C(C)NC1=O CZQGOIXSJFKZPT-UHFFFAOYSA-N 0.000 claims description 2
• SXFSERCDFHFHJK-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-[4-(dimethylsulfamoyl)phenyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C1=CC=C(S(=O)(=O)N(C)C)C=C1 SXFSERCDFHFHJK-UHFFFAOYSA-N 0.000 claims description 2
• YJGGPWSQBLSTLJ-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-[4-(dimethylsulfamoyl)phenyl]-3-methyl-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=C(C)C2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C1=CC=C(S(=O)(=O)N(C)C)C=C1 YJGGPWSQBLSTLJ-UHFFFAOYSA-N 0.000 claims description 2
• AKBZTJSWWZBIFH-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-[4-(methanesulfonamido)phenyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C1=CC=C(NS(C)(=O)=O)C=C1 AKBZTJSWWZBIFH-UHFFFAOYSA-N 0.000 claims description 2
• KLLPIDYLSWTUIN-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-[4-(methylcarbamoyl)phenyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=CC(C(=O)NC)=CC=C1C1=CC(C(=O)NCC=2C(NC(C)=CC=2C)=O)=C(C=NN2C(C)C)C2=N1 KLLPIDYLSWTUIN-UHFFFAOYSA-N 0.000 claims description 2
• MDSJORDMNXSQSC-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-[4-(methylsulfamoyl)phenyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=CC(S(=O)(=O)NC)=CC=C1C1=CC(C(=O)NCC=2C(NC(C)=CC=2C)=O)=C(C=NN2C(C)C)C2=N1 MDSJORDMNXSQSC-UHFFFAOYSA-N 0.000 claims description 2
• GBVZGIPBVWHTPF-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-[6-(methylcarbamoyl)pyridin-3-yl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=NC(C(=O)NC)=CC=C1C1=CC(C(=O)NCC=2C(NC(C)=CC=2C)=O)=C(C=NN2C(C)C)C2=N1 GBVZGIPBVWHTPF-UHFFFAOYSA-N 0.000 claims description 2
• FWXFWFSWSFPYIC-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-[6-(methylsulfamoyl)pyridin-3-yl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=NC(S(=O)(=O)NC)=CC=C1C1=CC(C(=O)NCC=2C(NC(C)=CC=2C)=O)=C(C=NN2C(C)C)C2=N1 FWXFWFSWSFPYIC-UHFFFAOYSA-N 0.000 claims description 2
• RENWHTRYJDRPJJ-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-methyl-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=C(C)N=C2N(C(C)C)N=CC2=C1C(=O)NCC1=C(C)C=C(C)NC1=O RENWHTRYJDRPJJ-UHFFFAOYSA-N 0.000 claims description 2
• ZZVBQHITBBGRCU-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-phenyl-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C1=CC=CC=C1 ZZVBQHITBBGRCU-UHFFFAOYSA-N 0.000 claims description 2
• BNUXDHYJYYPKDG-UHFFFAOYSA-N n-[(4-cyclohexyl-6-methyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-yl-6-pyridin-4-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C2CCCCC2)=O)C=C1C1=CC=NC=C1 BNUXDHYJYYPKDG-UHFFFAOYSA-N 0.000 claims description 2
• OZPJVSPZDPAKRN-UHFFFAOYSA-N n-[(4-cyclohexyl-6-methyl-2-oxo-1h-pyridin-3-yl)methyl]-6-cyclopropyl-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C2CCCCC2)=O)C=C1C1CC1 OZPJVSPZDPAKRN-UHFFFAOYSA-N 0.000 claims description 2
• OTXZCSZGICIBRE-UHFFFAOYSA-N n-[(4-cyclopropyl-6-methyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-yl-6-pyridin-4-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C2CC2)=O)C=C1C1=CC=NC=C1 OTXZCSZGICIBRE-UHFFFAOYSA-N 0.000 claims description 2
• MMOQOQZQWHKDKV-UHFFFAOYSA-N n-[(4-methyl-2-oxo-6-propyl-1h-pyridin-3-yl)methyl]-1-propan-2-yl-6-pyridin-4-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound O=C1NC(CCC)=CC(C)=C1CNC(=O)C1=CC(C=2C=CN=CC=2)=NC2=C1C=NN2C(C)C MMOQOQZQWHKDKV-UHFFFAOYSA-N 0.000 claims description 2
• LGVTYHNKQRPTBZ-UHFFFAOYSA-N n-[(5-fluoro-4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-yl-6-pyridin-4-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=C(F)C=2C)=O)C=C1C1=CC=NC=C1 LGVTYHNKQRPTBZ-UHFFFAOYSA-N 0.000 claims description 2
• PETSJQBBHVYOOQ-UHFFFAOYSA-N n-[(6-ethyl-4-methyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-yl-6-pyridin-4-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound O=C1NC(CC)=CC(C)=C1CNC(=O)C1=CC(C=2C=CN=CC=2)=NC2=C1C=NN2C(C)C PETSJQBBHVYOOQ-UHFFFAOYSA-N 0.000 claims description 2
• DCBXUYVKNBIIEC-UHFFFAOYSA-N n-[(6-methyl-2-oxo-4-phenyl-1h-pyridin-3-yl)methyl]-1-propan-2-yl-6-pyridin-4-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C=2C=CC=CC=2)=O)C=C1C1=CC=NC=C1 DCBXUYVKNBIIEC-UHFFFAOYSA-N 0.000 claims description 2
• UHUSXQZYBIFRSI-UHFFFAOYSA-N n-[(6-methyl-2-oxo-4-propan-2-yl-1h-pyridin-3-yl)methyl]-1-propan-2-yl-6-pyridin-4-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=C(C)NC(=O)C(CNC(=O)C=2C=3C=NN(C=3N=C(C=2)C=2C=CN=CC=2)C(C)C)=C1C(C)C UHUSXQZYBIFRSI-UHFFFAOYSA-N 0.000 claims description 2
• DJCPQWZBLRFOMD-UHFFFAOYSA-N n-[(6-methyl-2-oxo-4-propyl-1h-pyridin-3-yl)methyl]-1-propan-2-yl-6-pyridin-4-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=C(C)NC(=O)C(CNC(=O)C=2C=3C=NN(C=3N=C(C=2)C=2C=CN=CC=2)C(C)C)=C1CCC DJCPQWZBLRFOMD-UHFFFAOYSA-N 0.000 claims description 2
• 201000002528 pancreatic cancer Diseases 0.000 claims description 2
• 208000008443 pancreatic carcinoma Diseases 0.000 claims description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
• 208000011580 syndromic disease Diseases 0.000 claims description 2
• 201000005112 urinary bladder cancer Diseases 0.000 claims description 2
• 125000005843 halogen group Chemical group 0.000 claims 7
• BTSZGPWBSCFUQV-UHFFFAOYSA-N 1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=CN=C2N(C(C)C)N=CC2=C1C(N)=O BTSZGPWBSCFUQV-UHFFFAOYSA-N 0.000 claims 3
• 208000008839 Kidney Neoplasms Diseases 0.000 claims 2
• 206010038389 Renal cancer Diseases 0.000 claims 2
• 208000024770 Thyroid neoplasm Diseases 0.000 claims 2
• 201000010982 kidney cancer Diseases 0.000 claims 2
• 201000002510 thyroid cancer Diseases 0.000 claims 2
• JCWWOICHWDKSPS-UHFFFAOYSA-N 1,6-ditert-butyl-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-3-methylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C=12C(C)=NN(C(C)(C)C)C2=NC(C(C)(C)C)=CC=1C(=O)NCC1=C(C)C=C(C)NC1=O JCWWOICHWDKSPS-UHFFFAOYSA-N 0.000 claims 1
• CKQCYGJHRBQQHV-UHFFFAOYSA-N 1-(2-aminoethyl)-6-cyclopropyl-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]pyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound O=C1NC(C)=CC(C)=C1CNC(=O)C1=CC(C2CC2)=NC2=C1C=NN2CCN CKQCYGJHRBQQHV-UHFFFAOYSA-N 0.000 claims 1
• ZOZATYKUQBINTC-UHFFFAOYSA-N 1-tert-butyl-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-3-methyl-6-pyridin-3-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C=12C(C)=NN(C(C)(C)C)C2=NC(C=2C=NC=CC=2)=CC=1C(=O)NCC1=C(C)C=C(C)NC1=O ZOZATYKUQBINTC-UHFFFAOYSA-N 0.000 claims 1
• WFAPQHAQUNZYKQ-UHFFFAOYSA-N 1-tert-butyl-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-(4-methoxyphenyl)-3-methylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=CC(OC)=CC=C1C1=CC(C(=O)NCC=2C(NC(C)=CC=2C)=O)=C(C(C)=NN2C(C)(C)C)C2=N1 WFAPQHAQUNZYKQ-UHFFFAOYSA-N 0.000 claims 1
• 206010005969 Bone giant cell tumour Diseases 0.000 claims 1
• 206010009944 Colon cancer Diseases 0.000 claims 1
• 208000012609 Cowden disease Diseases 0.000 claims 1
• 201000002847 Cowden syndrome Diseases 0.000 claims 1
• 208000005726 Inflammatory Breast Neoplasms Diseases 0.000 claims 1
• 206010021980 Inflammatory carcinoma of the breast Diseases 0.000 claims 1
• 208000008770 Multiple Hamartoma Syndrome Diseases 0.000 claims 1
• 206010060862 Prostate cancer Diseases 0.000 claims 1
• 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
• 208000005718 Stomach Neoplasms Diseases 0.000 claims 1
• 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
• 201000000053 blastoma Diseases 0.000 claims 1
• 201000011143 bone giant cell tumor Diseases 0.000 claims 1
• 208000029742 colonic neoplasm Diseases 0.000 claims 1
• 201000008184 embryoma Diseases 0.000 claims 1
• 206010017758 gastric cancer Diseases 0.000 claims 1
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
• 201000004653 inflammatory breast carcinoma Diseases 0.000 claims 1
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 1
• HFENIZQGGJKRRU-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-yl-6-[4-(1h-pyrazol-4-yl)phenyl]pyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C(C=C1)=CC=C1C=1C=NNC=1 HFENIZQGGJKRRU-UHFFFAOYSA-N 0.000 claims 1
• SHDVMUJMBBILPO-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-3-methyl-1-propan-2-yl-6-pyridin-4-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=C(C)C2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C1=CC=NC=C1 SHDVMUJMBBILPO-UHFFFAOYSA-N 0.000 claims 1
• DEHLJNLCDLWSGP-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-(2-nitrophenyl)-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C1=CC=CC=C1[N+]([O-])=O DEHLJNLCDLWSGP-UHFFFAOYSA-N 0.000 claims 1
• VQFJTVSOZHCIFN-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-(4-methoxyphenyl)-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=CC(OC)=CC=C1C1=CC(C(=O)NCC=2C(NC(C)=CC=2C)=O)=C(C=NN2C(C)C)C2=N1 VQFJTVSOZHCIFN-UHFFFAOYSA-N 0.000 claims 1
• ATORHKLYJPRWNI-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-(4-methylsulfonylphenyl)-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C1=CC=C(S(C)(=O)=O)C=C1 ATORHKLYJPRWNI-UHFFFAOYSA-N 0.000 claims 1
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims 1
• 201000011549 stomach cancer Diseases 0.000 claims 1
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 255
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 199
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 183
• 238000005481 NMR spectroscopy Methods 0.000 description 176
• 239000007787 solid Substances 0.000 description 175
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 173
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 173
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 168
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 133
• 239000000203 mixture Substances 0.000 description 132
• 235000019439 ethyl acetate Nutrition 0.000 description 98
• 239000012467 final product Substances 0.000 description 98
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 93
• 239000000047 product Substances 0.000 description 91
• 239000000543 intermediate Substances 0.000 description 90
• HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 89
• 239000011541 reaction mixture Substances 0.000 description 85
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 74
• 239000003480 eluent Substances 0.000 description 63
• 238000010898 silica gel chromatography Methods 0.000 description 56
• 238000011282 treatment Methods 0.000 description 49
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 45
• 239000000243 solution Substances 0.000 description 45
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 42
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 40
• 239000012043 crude product Substances 0.000 description 39
• 238000000034 method Methods 0.000 description 37
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
• 238000001816 cooling Methods 0.000 description 36
• 230000000694 effects Effects 0.000 description 36
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 34
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 34
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
• FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 33
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 33
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
• 239000002904 solvent Substances 0.000 description 33
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 30
• IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 29
• 239000012044 organic layer Substances 0.000 description 27
• 238000003756 stirring Methods 0.000 description 26
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
• 239000002246 antineoplastic agent Substances 0.000 description 23
• 125000001475 halogen functional group Chemical group 0.000 description 23
• 238000010992 reflux Methods 0.000 description 23
• 239000000741 silica gel Substances 0.000 description 23
• 229910002027 silica gel Inorganic materials 0.000 description 23
• 235000002639 sodium chloride Nutrition 0.000 description 23
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 22
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
• 239000012267 brine Substances 0.000 description 22
• 239000003112 inhibitor Substances 0.000 description 22
• 230000000670 limiting effect Effects 0.000 description 22
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 21
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 21
• YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 21
• 239000012071 phase Substances 0.000 description 21
• 210000004027 cell Anatomy 0.000 description 20
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 20
• 229910000029 sodium carbonate Inorganic materials 0.000 description 20
• 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 19
• 206010065553 Bone marrow failure Diseases 0.000 description 19
• 102100038970 Histone-lysine N-methyltransferase EZH2 Human genes 0.000 description 19
• 101000882127 Homo sapiens Histone-lysine N-methyltransferase EZH2 Proteins 0.000 description 19
• 230000022131 cell cycle Effects 0.000 description 19
• 238000004007 reversed phase HPLC Methods 0.000 description 19
• 239000000725 suspension Substances 0.000 description 19
• 101150003085 Pdcl gene Proteins 0.000 description 18
• 239000003795 chemical substances by application Substances 0.000 description 17
• 235000017557 sodium bicarbonate Nutrition 0.000 description 17
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 17
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 16
• 239000000706 filtrate Substances 0.000 description 16
• 108020004414 DNA Proteins 0.000 description 15
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
• 239000003814 drug Substances 0.000 description 15
• 230000002829 reductive effect Effects 0.000 description 15
• PCJPGNCABBDNJU-UHFFFAOYSA-N 3-(aminomethyl)-4,6-dimethyl-1h-pyridin-2-one Chemical compound CC1=CC(C)=C(CN)C(=O)N1 PCJPGNCABBDNJU-UHFFFAOYSA-N 0.000 description 14
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 14
• 230000035484 reaction time Effects 0.000 description 14
• 230000002401 inhibitory effect Effects 0.000 description 13
• 239000010410 layer Substances 0.000 description 13
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
• WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 12
• RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 11
• 229910021529 ammonia Inorganic materials 0.000 description 11
• 238000006243 chemical reaction Methods 0.000 description 11
• 229940127089 cytotoxic agent Drugs 0.000 description 11
• 229940079593 drug Drugs 0.000 description 11
• 238000001556 precipitation Methods 0.000 description 11
• MHKXVJFDESXWFH-UHFFFAOYSA-N ethyl 4-cyclopropyl-2,4-dioxobutanoate Chemical compound CCOC(=O)C(=O)CC(=O)C1CC1 MHKXVJFDESXWFH-UHFFFAOYSA-N 0.000 description 10
• 238000002347 injection Methods 0.000 description 10
• 239000007924 injection Substances 0.000 description 10
• 239000011734 sodium Substances 0.000 description 10
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
• 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 9
• 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 9
• 108010033040 Histones Proteins 0.000 description 9
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 9
• 230000018199 S phase Effects 0.000 description 9
• 208000009956 adenocarcinoma Diseases 0.000 description 9
• 238000001704 evaporation Methods 0.000 description 9
• 230000008020 evaporation Effects 0.000 description 9
• 239000003921 oil Substances 0.000 description 9
• 230000008569 process Effects 0.000 description 9
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
• 239000012265 solid product Substances 0.000 description 9
• PBRNAFCVYDLODR-UHFFFAOYSA-N 1-propan-2-yl-6-pyridin-4-ylpyrazolo[3,4-b]pyridine-4-carboxylic acid Chemical compound N1=C2N(C(C)C)N=CC2=C(C(O)=O)C=C1C1=CC=NC=C1 PBRNAFCVYDLODR-UHFFFAOYSA-N 0.000 description 8
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 8
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
• 239000008346 aqueous phase Substances 0.000 description 8
• 125000004432 carbon atom Chemical group C* 0.000 description 8
• 230000006870 function Effects 0.000 description 8
• 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 8
• 238000010438 heat treatment Methods 0.000 description 8
• 235000019198 oils Nutrition 0.000 description 8
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 8
• 239000000843 powder Substances 0.000 description 8
• 125000003107 substituted aryl group Chemical group 0.000 description 8
• 238000003786 synthesis reaction Methods 0.000 description 8
• YZDILIKIHKVAHO-UHFFFAOYSA-N 6-cyclopropyl-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxylic acid Chemical compound N1=C2N(C(C)C)N=CC2=C(C(O)=O)C=C1C1CC1 YZDILIKIHKVAHO-UHFFFAOYSA-N 0.000 description 7
• 108010092160 Dactinomycin Proteins 0.000 description 7
• 102000006947 Histones Human genes 0.000 description 7
• 239000002253 acid Substances 0.000 description 7
• 239000004480 active ingredient Substances 0.000 description 7
• 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 7
• 230000030833 cell death Effects 0.000 description 7
• 238000001914 filtration Methods 0.000 description 7
• GURKHSYORGJETM-WAQYZQTGSA-N irinotecan hydrochloride (anhydrous) Chemical compound Cl.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 GURKHSYORGJETM-WAQYZQTGSA-N 0.000 description 7
• 201000002364 leukopenia Diseases 0.000 description 7
• 239000007788 liquid Substances 0.000 description 7
• GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 7
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 7
• 239000002244 precipitate Substances 0.000 description 7
• 239000012453 solvate Substances 0.000 description 7
• 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 7
• FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 6
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
• DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 6
• 230000006820 DNA synthesis Effects 0.000 description 6
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 6
• 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 6
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
• 208000034578 Multiple myelomas Diseases 0.000 description 6
• 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 6
• 229930012538 Paclitaxel Natural products 0.000 description 6
• 206010035226 Plasma cell myeloma Diseases 0.000 description 6
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 6
• 229940122803 Vinca alkaloid Drugs 0.000 description 6
• RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 6
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 6
• 235000011114 ammonium hydroxide Nutrition 0.000 description 6
• 230000015572 biosynthetic process Effects 0.000 description 6
• 210000000481 breast Anatomy 0.000 description 6
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 6
• 229910000024 caesium carbonate Inorganic materials 0.000 description 6
• 229960004316 cisplatin Drugs 0.000 description 6
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 6
• DGJMPUGMZIKDRO-UHFFFAOYSA-N cyanoacetamide Chemical compound NC(=O)CC#N DGJMPUGMZIKDRO-UHFFFAOYSA-N 0.000 description 6
• 229960000684 cytarabine Drugs 0.000 description 6
• 150000004141 diterpene derivatives Chemical class 0.000 description 6
• VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 6
• 239000000284 extract Substances 0.000 description 6
• 229960002949 fluorouracil Drugs 0.000 description 6
• 229960005277 gemcitabine Drugs 0.000 description 6
• 238000004128 high performance liquid chromatography Methods 0.000 description 6
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
• 229940102223 injectable solution Drugs 0.000 description 6
• 239000000463 material Substances 0.000 description 6
• 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 6
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
• 229960001592 paclitaxel Drugs 0.000 description 6
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
• 108090000623 proteins and genes Proteins 0.000 description 6
• 230000019491 signal transduction Effects 0.000 description 6
• 206010041823 squamous cell carcinoma Diseases 0.000 description 6
• NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 6
• UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 6
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 5
• STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 5
• 206010000830 Acute leukaemia Diseases 0.000 description 5
• 108010006654 Bleomycin Proteins 0.000 description 5
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 5
• 208000017604 Hodgkin disease Diseases 0.000 description 5
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 5
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 5
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 5
• 208000024313 Testicular Neoplasms Diseases 0.000 description 5
• 206010057644 Testis cancer Diseases 0.000 description 5
• 108091008605 VEGF receptors Proteins 0.000 description 5
• 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 5
• 229940100198 alkylating agent Drugs 0.000 description 5
• 239000002168 alkylating agent Substances 0.000 description 5
• 239000012298 atmosphere Substances 0.000 description 5
• 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 5
• 229960001561 bleomycin Drugs 0.000 description 5
• OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 5
• 229940127093 camptothecin Drugs 0.000 description 5
• JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 5
• 238000000576 coating method Methods 0.000 description 5
• 238000002648 combination therapy Methods 0.000 description 5
• NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 5
• 229960000640 dactinomycin Drugs 0.000 description 5
• STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin 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(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 5
• 239000003085 diluting agent Substances 0.000 description 5
• 208000035475 disorder Diseases 0.000 description 5
• 229960003668 docetaxel Drugs 0.000 description 5
• 239000002552 dosage form Substances 0.000 description 5
• 239000000839 emulsion Substances 0.000 description 5
• GBTWSRNPJUSTML-UHFFFAOYSA-N ethyl 6-cyclopropyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylate Chemical compound N=1C=2NN=CC=2C(C(=O)OCC)=CC=1C1CC1 GBTWSRNPJUSTML-UHFFFAOYSA-N 0.000 description 5
• 229960005420 etoposide Drugs 0.000 description 5
• 238000009472 formulation Methods 0.000 description 5
• 239000005457 ice water Substances 0.000 description 5
• 230000005764 inhibitory process Effects 0.000 description 5
• 210000004072 lung Anatomy 0.000 description 5
• 230000007246 mechanism Effects 0.000 description 5
• 229960001428 mercaptopurine Drugs 0.000 description 5
• 229960000485 methotrexate Drugs 0.000 description 5
• 238000002638 palliative care Methods 0.000 description 5
• 239000000546 pharmaceutical excipient Substances 0.000 description 5
• 239000001632 sodium acetate Substances 0.000 description 5
• 235000017281 sodium acetate Nutrition 0.000 description 5
• 229910052938 sodium sulfate Inorganic materials 0.000 description 5
• 235000011152 sodium sulphate Nutrition 0.000 description 5
• VNFWTIYUKDMAOP-UHFFFAOYSA-N sphos Chemical compound COC1=CC=CC(OC)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 VNFWTIYUKDMAOP-UHFFFAOYSA-N 0.000 description 5
• 238000010561 standard procedure Methods 0.000 description 5
• 125000001424 substituent group Chemical group 0.000 description 5
• 229960001278 teniposide Drugs 0.000 description 5
• 201000003120 testicular cancer Diseases 0.000 description 5
• 206010043554 thrombocytopenia Diseases 0.000 description 5
• 229960003087 tioguanine Drugs 0.000 description 5
• 229960000303 topotecan Drugs 0.000 description 5
• 239000003039 volatile agent Substances 0.000 description 5
• DELJOESCKJGFML-RQOWECAXSA-N (z)-3-aminobut-2-enenitrile Chemical compound C\C(N)=C\C#N DELJOESCKJGFML-RQOWECAXSA-N 0.000 description 4
• FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 4
• QHRUXDXIVIYFJJ-UHFFFAOYSA-N 3-(aminomethyl)-1h-pyridin-2-one Chemical class NCC1=CC=CNC1=O QHRUXDXIVIYFJJ-UHFFFAOYSA-N 0.000 description 4
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
• KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 4
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 4
• 102000003915 DNA Topoisomerases Human genes 0.000 description 4
• 108090000323 DNA Topoisomerases Proteins 0.000 description 4
• 206010024612 Lipoma Diseases 0.000 description 4
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 4
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 4
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
• 102000004243 Tubulin Human genes 0.000 description 4
• 108090000704 Tubulin Proteins 0.000 description 4
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 4
• 208000007502 anemia Diseases 0.000 description 4
• 230000000340 anti-metabolite Effects 0.000 description 4
• 229940100197 antimetabolite Drugs 0.000 description 4
• 239000002256 antimetabolite Substances 0.000 description 4
• 230000006907 apoptotic process Effects 0.000 description 4
• 125000005015 aryl alkynyl group Chemical group 0.000 description 4
• 239000002585 base Substances 0.000 description 4
• IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 4
• FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 4
• 239000002775 capsule Substances 0.000 description 4
• 229910002091 carbon monoxide Inorganic materials 0.000 description 4
• 229960004562 carboplatin Drugs 0.000 description 4
• 229960005243 carmustine Drugs 0.000 description 4
• 239000003054 catalyst Substances 0.000 description 4
• 230000003197 catalytic effect Effects 0.000 description 4
• 229960004630 chlorambucil Drugs 0.000 description 4
• 239000011248 coating agent Substances 0.000 description 4
• 238000004440 column chromatography Methods 0.000 description 4
• 229960004397 cyclophosphamide Drugs 0.000 description 4
• 229960003901 dacarbazine Drugs 0.000 description 4
• 229960000975 daunorubicin Drugs 0.000 description 4
• 238000001514 detection method Methods 0.000 description 4
• 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 4
• 229960004679 doxorubicin Drugs 0.000 description 4
• 238000000105 evaporative light scattering detection Methods 0.000 description 4
• 206010016629 fibroma Diseases 0.000 description 4
• 125000000524 functional group Chemical group 0.000 description 4
• 201000011066 hemangioma Diseases 0.000 description 4
• 125000005312 heteroarylalkynyl group Chemical group 0.000 description 4
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
• 230000002779 inactivation Effects 0.000 description 4
• 230000001939 inductive effect Effects 0.000 description 4
• 239000004615 ingredient Substances 0.000 description 4
• 229960004768 irinotecan Drugs 0.000 description 4
• 239000000314 lubricant Substances 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• 230000036210 malignancy Effects 0.000 description 4
• 229960001924 melphalan Drugs 0.000 description 4
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 4
• 229910052697 platinum Inorganic materials 0.000 description 4
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
• 229940002612 prodrug Drugs 0.000 description 4
• 239000000651 prodrug Substances 0.000 description 4
• 210000002307 prostate Anatomy 0.000 description 4
• 238000000746 purification Methods 0.000 description 4
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
• XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 4
• 238000011519 second-line treatment Methods 0.000 description 4
• 230000011664 signaling Effects 0.000 description 4
• JXLYSJRDGCGARV-CFWMRBGOSA-N vinblastine 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-CFWMRBGOSA-N 0.000 description 4
• 229960003048 vinblastine Drugs 0.000 description 4
• 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 4
• 229960004528 vincristine Drugs 0.000 description 4
• 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 4
• GBABOYUKABKIAF-IELIFDKJSA-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-IELIFDKJSA-N 0.000 description 4
• 229960002066 vinorelbine Drugs 0.000 description 4
• 238000005406 washing Methods 0.000 description 4
• 229910052725 zinc Inorganic materials 0.000 description 4
• 239000011701 zinc Substances 0.000 description 4
• FFPQELNXDVTLEW-UHFFFAOYSA-N (6-morpholin-4-ylpyridin-3-yl)boronic acid Chemical compound N1=CC(B(O)O)=CC=C1N1CCOCC1 FFPQELNXDVTLEW-UHFFFAOYSA-N 0.000 description 3
• JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical class NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 description 3
• JSRPCAOFGDZBRH-UHFFFAOYSA-N 3-(aminomethyl)-6-methyl-4-propan-2-yl-1h-pyridin-2-one Chemical compound CC(C)C=1C=C(C)NC(=O)C=1CN JSRPCAOFGDZBRH-UHFFFAOYSA-N 0.000 description 3
• 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 3
• LQVSXEXWXILGBH-UHFFFAOYSA-N 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dihydrobenzimidazol-2-one Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(NC(=O)N2)C2=C1 LQVSXEXWXILGBH-UHFFFAOYSA-N 0.000 description 3
• NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 description 3
• OCSWHADWFJTNAZ-UHFFFAOYSA-N 5-methyl-2-propan-2-ylpyrazol-3-amine Chemical compound CC(C)N1N=C(C)C=C1N OCSWHADWFJTNAZ-UHFFFAOYSA-N 0.000 description 3
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• 102000053602 DNA Human genes 0.000 description 3
• 102000004190 Enzymes Human genes 0.000 description 3
• 108090000790 Enzymes Proteins 0.000 description 3
• 201000008808 Fibrosarcoma Diseases 0.000 description 3
• 108010010803 Gelatin Proteins 0.000 description 3
• 102000003964 Histone deacetylase Human genes 0.000 description 3
• 108090000353 Histone deacetylase Proteins 0.000 description 3
• 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 3
• 208000007766 Kaposi sarcoma Diseases 0.000 description 3
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 3
• 206010027476 Metastases Diseases 0.000 description 3
• 206010028116 Mucosal inflammation Diseases 0.000 description 3
• 201000010927 Mucositis Diseases 0.000 description 3
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
• 206010028813 Nausea Diseases 0.000 description 3
• 229910019142 PO4 Inorganic materials 0.000 description 3
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 3
• 108091005682 Receptor kinases Proteins 0.000 description 3
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
• 206010043276 Teratoma Diseases 0.000 description 3
• 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 3
• 206010047700 Vomiting Diseases 0.000 description 3
• 230000002378 acidificating effect Effects 0.000 description 3
• 125000004442 acylamino group Chemical group 0.000 description 3
• 239000004037 angiogenesis inhibitor Substances 0.000 description 3
• 229940121369 angiogenesis inhibitor Drugs 0.000 description 3
• 229940041181 antineoplastic drug Drugs 0.000 description 3
• 229960002756 azacitidine Drugs 0.000 description 3
• 238000010945 base-catalyzed hydrolysis reactiony Methods 0.000 description 3
• 239000011230 binding agent Substances 0.000 description 3
• 239000008280 blood Substances 0.000 description 3
• 210000004369 blood Anatomy 0.000 description 3
• 229940045348 brown mixture Drugs 0.000 description 3
• 229960002092 busulfan Drugs 0.000 description 3
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
• 230000004663 cell proliferation Effects 0.000 description 3
• 210000003679 cervix uteri Anatomy 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 210000001072 colon Anatomy 0.000 description 3
• 239000013058 crude material Substances 0.000 description 3
• 238000011161 development Methods 0.000 description 3
• 230000018109 developmental process Effects 0.000 description 3
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
• 239000007884 disintegrant Substances 0.000 description 3
• 239000002024 ethyl acetate extract Substances 0.000 description 3
• 238000002474 experimental method Methods 0.000 description 3
• 235000019253 formic acid Nutrition 0.000 description 3
• 229920000159 gelatin Polymers 0.000 description 3
• 239000008273 gelatin Substances 0.000 description 3
• 235000019322 gelatine Nutrition 0.000 description 3
• 235000011852 gelatine desserts Nutrition 0.000 description 3
• 230000012010 growth Effects 0.000 description 3
• 239000003102 growth factor Substances 0.000 description 3
• 210000003128 head Anatomy 0.000 description 3
• 239000008241 heterogeneous mixture Substances 0.000 description 3
• 230000011278 mitosis Effects 0.000 description 3
• 230000008693 nausea Effects 0.000 description 3
• 210000003739 neck Anatomy 0.000 description 3
• 208000004235 neutropenia Diseases 0.000 description 3
• 239000002777 nucleoside Substances 0.000 description 3
• 150000003833 nucleoside derivatives Chemical class 0.000 description 3
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
• 229910052763 palladium Inorganic materials 0.000 description 3
• LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 3
• 235000021317 phosphate Nutrition 0.000 description 3
• 229910052700 potassium Inorganic materials 0.000 description 3
• 239000011591 potassium Substances 0.000 description 3
• 238000002360 preparation method Methods 0.000 description 3
• 230000002062 proliferating effect Effects 0.000 description 3
• 125000006239 protecting group Chemical group 0.000 description 3
• 239000002002 slurry Substances 0.000 description 3
• 229910052708 sodium Inorganic materials 0.000 description 3
• 235000009518 sodium iodide Nutrition 0.000 description 3
• 210000002784 stomach Anatomy 0.000 description 3
• 239000000126 substance Substances 0.000 description 3
• 238000006467 substitution reaction Methods 0.000 description 3
• 230000004083 survival effect Effects 0.000 description 3
• 238000002560 therapeutic procedure Methods 0.000 description 3
• 230000008673 vomiting Effects 0.000 description 3
• 238000010792 warming Methods 0.000 description 3
• 239000001993 wax Substances 0.000 description 3
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 2
• NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
• VYEWTHXZHHATTA-UHFFFAOYSA-N (4-acetamidophenyl)boronic acid Chemical compound CC(=O)NC1=CC=C(B(O)O)C=C1 VYEWTHXZHHATTA-UHFFFAOYSA-N 0.000 description 2
• FOVRGQUEGRCWPD-UHFFFAOYSA-N (5aR)-9t-beta-D-Glucopyranosyloxy-5t-(4-hydroxy-3,5-dimethoxy-phenyl)-(5ar,8at)-5,8,8a,9-tetrahydro-5aH-furo[3',4';6,7]naphtho[2,3-d][1,3]dioxol-6-on Natural products COC1=C(O)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(OC3C(C(O)C(O)C(CO)O3)O)C3C2C(OC3)=O)=C1 FOVRGQUEGRCWPD-UHFFFAOYSA-N 0.000 description 2
• MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical compound C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 description 2
• JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 2
• BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 2
• FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 2
• AREDWLUEMFAGRO-UHFFFAOYSA-N 1-amino-6-cyclopropylpyrazolo[3,4-b]pyridine-4-carboxylic acid Chemical compound N1=C2N(N)N=CC2=C(C(O)=O)C=C1C1CC1 AREDWLUEMFAGRO-UHFFFAOYSA-N 0.000 description 2
• KZRXNRYUGKUZGD-UHFFFAOYSA-N 1-benzyl-4-bromo-6-methylpyrazolo[3,4-b]pyridine Chemical compound C12=NC(C)=CC(Br)=C2C=NN1CC1=CC=CC=C1 KZRXNRYUGKUZGD-UHFFFAOYSA-N 0.000 description 2
• AOJKMVYSCVMEJS-UHFFFAOYSA-N 1-benzyl-6-methyl-7H-pyrazolo[3,4-b]pyridin-4-one Chemical compound C12=NC(C)=CC(O)=C2C=NN1CC1=CC=CC=C1 AOJKMVYSCVMEJS-UHFFFAOYSA-N 0.000 description 2
• SFHUVAQSSDOJCC-UHFFFAOYSA-N 1-benzyl-6-methylpyrazolo[3,4-b]pyridine-4-carbonitrile Chemical compound C12=NC(C)=CC(C#N)=C2C=NN1CC1=CC=CC=C1 SFHUVAQSSDOJCC-UHFFFAOYSA-N 0.000 description 2
• QFCMNCAATMQLQF-UHFFFAOYSA-N 1-benzyl-6-methylpyrazolo[3,4-b]pyridine-4-carboxylic acid Chemical compound C12=NC(C)=CC(C(O)=O)=C2C=NN1CC1=CC=CC=C1 QFCMNCAATMQLQF-UHFFFAOYSA-N 0.000 description 2
• SUECOQMJRPXZFF-UHFFFAOYSA-N 1-cyclobutyl-6-cyclopropyl-3-methylpyrazolo[3,4-b]pyridine-4-carboxylic acid Chemical compound C12=NC(C3CC3)=CC(C(O)=O)=C2C(C)=NN1C1CCC1 SUECOQMJRPXZFF-UHFFFAOYSA-N 0.000 description 2
• HIOVJASWVVPYFV-UHFFFAOYSA-N 1-cyclohexyl-6-cyclopropyl-3-methylpyrazolo[3,4-b]pyridine-4-carboxylic acid Chemical compound C12=NC(C3CC3)=CC(C(O)=O)=C2C(C)=NN1C1CCCCC1 HIOVJASWVVPYFV-UHFFFAOYSA-N 0.000 description 2
• UQRGISZTLGTEQP-UHFFFAOYSA-N 1-cyclopentyl-6-cyclopropyl-3-methylpyrazolo[3,4-b]pyridine-4-carboxylic acid Chemical compound C12=NC(C3CC3)=CC(C(O)=O)=C2C(C)=NN1C1CCCC1 UQRGISZTLGTEQP-UHFFFAOYSA-N 0.000 description 2
• KLCGMDWRXACELA-UHFFFAOYSA-N 1-cyclopropylbutane-1,3-dione Chemical compound CC(=O)CC(=O)C1CC1 KLCGMDWRXACELA-UHFFFAOYSA-N 0.000 description 2
• HVCFCNAITDHQFX-UHFFFAOYSA-N 1-cyclopropylethanone Chemical compound CC(=O)C1CC1 HVCFCNAITDHQFX-UHFFFAOYSA-N 0.000 description 2
• KVQXFNGVIIPCSX-UHFFFAOYSA-N 1-methyl-4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]piperazine Chemical compound C1CN(C)CCN1C1=CC=C(B2OC(C)(C)C(C)(C)O2)C=N1 KVQXFNGVIIPCSX-UHFFFAOYSA-N 0.000 description 2
• VGFWZJFGKJJENC-UHFFFAOYSA-N 1-tert-butyl-3-methyl-6-oxo-7H-pyrazolo[3,4-b]pyridine-4-carboxylic acid Chemical compound N1C(=O)C=C(C(O)=O)C2=C1N(C(C)(C)C)N=C2C VGFWZJFGKJJENC-UHFFFAOYSA-N 0.000 description 2
• DVXPVWRTRDDTHT-UHFFFAOYSA-N 1-tert-butyl-6-chloro-3-methylpyrazolo[3,4-b]pyridine-4-carboxylic acid Chemical compound ClC1=CC(C(O)=O)=C2C(C)=NN(C(C)(C)C)C2=N1 DVXPVWRTRDDTHT-UHFFFAOYSA-N 0.000 description 2
• ICILRPWQMYTXTM-UHFFFAOYSA-N 1-tert-butyl-6-cyclopropyl-3-methylpyrazolo[3,4-b]pyridine-4-carboxylic acid Chemical compound C=1C(C(O)=O)=C2C(C)=NN(C(C)(C)C)C2=NC=1C1CC1 ICILRPWQMYTXTM-UHFFFAOYSA-N 0.000 description 2
• JEBIFRSQWFZFMT-UHFFFAOYSA-N 2-[(4-methoxyphenyl)methyl]pyrazol-3-amine Chemical compound C1=CC(OC)=CC=C1CN1C(N)=CC=N1 JEBIFRSQWFZFMT-UHFFFAOYSA-N 0.000 description 2
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 2
• CZTSQAJDJOITRC-UHFFFAOYSA-N 2-cyclobutyl-5-methylpyrazol-3-amine Chemical compound N1=C(C)C=C(N)N1C1CCC1 CZTSQAJDJOITRC-UHFFFAOYSA-N 0.000 description 2
• MNOPOOFSVGTODG-UHFFFAOYSA-N 2-cyclopentyl-5-methylpyrazol-3-amine Chemical compound N1=C(C)C=C(N)N1C1CCCC1 MNOPOOFSVGTODG-UHFFFAOYSA-N 0.000 description 2
• AHRQLLLOCPXPCS-UHFFFAOYSA-N 2-propan-2-ylpyrazol-3-amine Chemical compound CC(C)N1N=CC=C1N AHRQLLLOCPXPCS-UHFFFAOYSA-N 0.000 description 2
• CMPRMWFPGYBHTQ-UHFFFAOYSA-N 2-tert-butyl-5-methylpyrazol-3-amine Chemical compound CC=1C=C(N)N(C(C)(C)C)N=1 CMPRMWFPGYBHTQ-UHFFFAOYSA-N 0.000 description 2
• RLLUYBQTEVLUMS-UHFFFAOYSA-N 3-(aminomethyl)-4-cyclohexyl-6-methyl-1h-pyridin-2-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.O=C1NC(C)=CC(C2CCCCC2)=C1CN RLLUYBQTEVLUMS-UHFFFAOYSA-N 0.000 description 2
• RUEXFLOOPCZLPC-UHFFFAOYSA-N 3-(aminomethyl)-4-methyl-6-propyl-1h-pyridin-2-one Chemical compound CCCC1=CC(C)=C(CN)C(=O)N1 RUEXFLOOPCZLPC-UHFFFAOYSA-N 0.000 description 2
• AGQUJRIEBZYNDB-UHFFFAOYSA-N 3-(aminomethyl)-6-cyclopropyl-4-methyl-1h-pyridin-2-one;hydrochloride Chemical compound Cl.N1C(=O)C(CN)=C(C)C=C1C1CC1 AGQUJRIEBZYNDB-UHFFFAOYSA-N 0.000 description 2
• WQHDTHDJPDGYLZ-UHFFFAOYSA-N 3-(aminomethyl)-6-methyl-4-(trifluoromethyl)-1h-pyridin-2-one Chemical compound CC1=CC(C(F)(F)F)=C(CN)C(=O)N1 WQHDTHDJPDGYLZ-UHFFFAOYSA-N 0.000 description 2
• JBKWKHWTUAUEFI-UHFFFAOYSA-N 3-(aminomethyl)-6-methyl-4-propyl-1h-pyridin-2-one Chemical compound CCCC=1C=C(C)NC(=O)C=1CN JBKWKHWTUAUEFI-UHFFFAOYSA-N 0.000 description 2
• MDWOQBMDDFJUOR-UHFFFAOYSA-N 3-methyl-6-oxo-1-propan-2-yl-7H-pyrazolo[3,4-b]pyridine-4-carboxylic acid Chemical compound OC(=O)C1=CC(=O)NC2=C1C(C)=NN2C(C)C MDWOQBMDDFJUOR-UHFFFAOYSA-N 0.000 description 2
• YVCVYCSAAZQOJI-JHQYFNNDSA-N 4'-demethylepipodophyllotoxin Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YVCVYCSAAZQOJI-JHQYFNNDSA-N 0.000 description 2
• ZZZPJCCGVJYNAH-UHFFFAOYSA-N 4-methyl-2-oxo-6-propyl-1h-pyridine-3-carbonitrile Chemical compound CCCC1=CC(C)=C(C#N)C(=O)N1 ZZZPJCCGVJYNAH-UHFFFAOYSA-N 0.000 description 2
• MQXANAGMQAYTMV-UHFFFAOYSA-N 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,1,3-benzoxadiazole Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC2=NON=C2C=C1 MQXANAGMQAYTMV-UHFFFAOYSA-N 0.000 description 2
• XAUDJQYHKZQPEU-KVQBGUIXSA-N 5-aza-2'-deoxycytidine Chemical compound O=C1N=C(N)N=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 XAUDJQYHKZQPEU-KVQBGUIXSA-N 0.000 description 2
• IKFFKLGLDGPWFJ-UHFFFAOYSA-N 5-bromo-n-methylpyridine-2-sulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Br)C=N1 IKFFKLGLDGPWFJ-UHFFFAOYSA-N 0.000 description 2
• SFUBOCVBYZCIFG-UHFFFAOYSA-N 5-methyl-2-(oxan-4-yl)pyrazol-3-amine Chemical compound N1=C(C)C=C(N)N1C1CCOCC1 SFUBOCVBYZCIFG-UHFFFAOYSA-N 0.000 description 2
• YWLXLRUDGLRYDR-ZHPRIASZSA-N 5beta,20-epoxy-1,7beta,10beta,13alpha-tetrahydroxy-9-oxotax-11-ene-2alpha,4alpha-diyl 4-acetate 2-benzoate Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](O)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 YWLXLRUDGLRYDR-ZHPRIASZSA-N 0.000 description 2
• MLBZAPHWNMNAJG-UHFFFAOYSA-N 6-chloro-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxylic acid Chemical compound C1=C(Cl)N=C2N(C(C)C)N=CC2=C1C(O)=O MLBZAPHWNMNAJG-UHFFFAOYSA-N 0.000 description 2
• HCNLJCWUXKHIRQ-UHFFFAOYSA-N 6-chloro-3-methyl-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxylic acid Chemical compound C1=C(Cl)N=C2N(C(C)C)N=C(C)C2=C1C(O)=O HCNLJCWUXKHIRQ-UHFFFAOYSA-N 0.000 description 2
• GULQTEYKOJRRSJ-UHFFFAOYSA-N 6-chloro-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-3-methyl-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=C(Cl)N=C2N(C(C)C)N=C(C)C2=C1C(=O)NCC1=C(C)C=C(C)NC1=O GULQTEYKOJRRSJ-UHFFFAOYSA-N 0.000 description 2
• DGKARBSLALXJEN-UHFFFAOYSA-N 6-cyclopropyl-1-(1-cyclopropylethyl)-3-methylpyrazolo[3,4-b]pyridine-4-carboxylic acid Chemical compound N1=C(C)C2=C(C(O)=O)C=C(C3CC3)N=C2N1C(C)C1CC1 DGKARBSLALXJEN-UHFFFAOYSA-N 0.000 description 2
• WPANNYNBUVRWFR-UHFFFAOYSA-N 6-cyclopropyl-1-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]pyrazolo[3,4-b]pyridine-4-carboxylic acid Chemical compound N1=C2N(CCNC(=O)OC(C)(C)C)N=CC2=C(C(O)=O)C=C1C1CC1 WPANNYNBUVRWFR-UHFFFAOYSA-N 0.000 description 2
• KVOJFHZWBXRJGZ-UHFFFAOYSA-N 6-cyclopropyl-1-ethylpyrazolo[3,4-b]pyridine-4-carboxylic acid Chemical compound N1=C2N(CC)N=CC2=C(C(O)=O)C=C1C1CC1 KVOJFHZWBXRJGZ-UHFFFAOYSA-N 0.000 description 2
• AMFWYYBVTMGMSH-UHFFFAOYSA-N 6-cyclopropyl-1-propylpyrazolo[3,4-b]pyridine-4-carboxylic acid Chemical compound N1=C2N(CCC)N=CC2=C(C(O)=O)C=C1C1CC1 AMFWYYBVTMGMSH-UHFFFAOYSA-N 0.000 description 2
• BXLXTQYKJKTMSL-UHFFFAOYSA-N 6-cyclopropyl-3-methyl-1-(1-methylpiperidin-4-yl)pyrazolo[3,4-b]pyridine-4-carboxylic acid Chemical compound C1CN(C)CCC1N1C2=NC(C3CC3)=CC(C(O)=O)=C2C(C)=N1 BXLXTQYKJKTMSL-UHFFFAOYSA-N 0.000 description 2
• HOCMPABWLIRUSQ-UHFFFAOYSA-N 6-cyclopropyl-3-methyl-1-pyridin-4-ylpyrazolo[3,4-b]pyridine-4-carboxylic acid Chemical compound C12=NC(C3CC3)=CC(C(O)=O)=C2C(C)=NN1C1=CC=NC=C1 HOCMPABWLIRUSQ-UHFFFAOYSA-N 0.000 description 2
• SMGBURLUQWAZGR-UHFFFAOYSA-N 6-cyclopropyl-4-methyl-2-oxo-1h-pyridine-3-carbonitrile Chemical compound N1C(=O)C(C#N)=C(C)C=C1C1CC1 SMGBURLUQWAZGR-UHFFFAOYSA-N 0.000 description 2
• UCEGMQCPDMISAQ-UHFFFAOYSA-N 6-oxo-1-propan-2-yl-7H-pyrazolo[3,4-b]pyridine-4-carboxylic acid Chemical compound OC(=O)C1=CC(=O)NC2=C1C=NN2C(C)C UCEGMQCPDMISAQ-UHFFFAOYSA-N 0.000 description 2
• NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 2
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 2
• 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 2
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 2
• 208000003200 Adenoma Diseases 0.000 description 2
• 206010001233 Adenoma benign Diseases 0.000 description 2
• 229920001817 Agar Polymers 0.000 description 2
• VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 2
• 201000004384 Alopecia Diseases 0.000 description 2
• 201000003076 Angiosarcoma Diseases 0.000 description 2
• 102400000068 Angiostatin Human genes 0.000 description 2
• 108010079709 Angiostatins Proteins 0.000 description 2
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 2
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 2
• 206010004593 Bile duct cancer Diseases 0.000 description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
• 206010007275 Carcinoid tumour Diseases 0.000 description 2
• 201000009030 Carcinoma Diseases 0.000 description 2
• 208000006332 Choriocarcinoma Diseases 0.000 description 2
• 108010077544 Chromatin Proteins 0.000 description 2
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
• 230000007067 DNA methylation Effects 0.000 description 2
• 229940123780 DNA topoisomerase I inhibitor Drugs 0.000 description 2
• 229940124087 DNA topoisomerase II inhibitor Drugs 0.000 description 2
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
• 102400001047 Endostatin Human genes 0.000 description 2
• 108010079505 Endostatins Proteins 0.000 description 2
• UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 2
• 230000005526 G1 to G0 transition Effects 0.000 description 2
• 206010064147 Gastrointestinal inflammation Diseases 0.000 description 2
• 208000032612 Glial tumor Diseases 0.000 description 2
• 206010018338 Glioma Diseases 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 2
• 108010009202 Growth Factor Receptors Proteins 0.000 description 2
• 102000009465 Growth Factor Receptors Human genes 0.000 description 2
• 208000001258 Hemangiosarcoma Diseases 0.000 description 2
• 102100039869 Histone H2B type F-S Human genes 0.000 description 2
• 101001035372 Homo sapiens Histone H2B type F-S Proteins 0.000 description 2
• 239000005551 L01XE03 - Erlotinib Substances 0.000 description 2
• 239000002136 L01XE07 - Lapatinib Substances 0.000 description 2
• XNRVGTHNYCNCFF-UHFFFAOYSA-N Lapatinib ditosylate monohydrate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1.CC1=CC=C(S(O)(=O)=O)C=C1.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 XNRVGTHNYCNCFF-UHFFFAOYSA-N 0.000 description 2
• 208000018142 Leiomyosarcoma Diseases 0.000 description 2
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
• 102000029749 Microtubule Human genes 0.000 description 2
• 108091022875 Microtubule Proteins 0.000 description 2
• 201000003793 Myelodysplastic syndrome Diseases 0.000 description 2
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 2
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 2
• 201000004404 Neurofibroma Diseases 0.000 description 2
• 108010047956 Nucleosomes Proteins 0.000 description 2
• 208000000035 Osteochondroma Diseases 0.000 description 2
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 2
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
• 239000004698 Polyethylene Substances 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 2
• 102000001253 Protein Kinase Human genes 0.000 description 2
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
• 229920002472 Starch Polymers 0.000 description 2
• 241001116498 Taxus baccata Species 0.000 description 2
• DPOPAJRDYZGTIR-UHFFFAOYSA-N Tetrazine Chemical compound C1=CN=NN=N1 DPOPAJRDYZGTIR-UHFFFAOYSA-N 0.000 description 2
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
• 101710183280 Topoisomerase Proteins 0.000 description 2
• 239000000365 Topoisomerase I Inhibitor Substances 0.000 description 2
• 239000000317 Topoisomerase II Inhibitor Substances 0.000 description 2
• 108010046308 Type II DNA Topoisomerases Proteins 0.000 description 2
• 102000007537 Type II DNA Topoisomerases Human genes 0.000 description 2
• DOQOQZHSIBBHMY-UHFFFAOYSA-N [4-(methylsulfamoyl)phenyl]boronic acid Chemical compound CNS(=O)(=O)C1=CC=C(B(O)O)C=C1 DOQOQZHSIBBHMY-UHFFFAOYSA-N 0.000 description 2
• 230000001594 aberrant effect Effects 0.000 description 2
• 230000002159 abnormal effect Effects 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 229930183665 actinomycin Natural products 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 239000008186 active pharmaceutical agent Substances 0.000 description 2
• 239000008272 agar Substances 0.000 description 2
• 235000010419 agar Nutrition 0.000 description 2
• 229940045714 alkyl sulfonate alkylating agent Drugs 0.000 description 2
• 150000008052 alkyl sulfonates Chemical class 0.000 description 2
• 230000029936 alkylation Effects 0.000 description 2
• 238000005804 alkylation reaction Methods 0.000 description 2
• 231100000360 alopecia Toxicity 0.000 description 2
• 229910052782 aluminium Inorganic materials 0.000 description 2
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
• 230000033115 angiogenesis Effects 0.000 description 2
• RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
• 208000022531 anorexia Diseases 0.000 description 2
• 229940045799 anthracyclines and related substance Drugs 0.000 description 2
• 239000003242 anti bacterial agent Substances 0.000 description 2
• 230000001093 anti-cancer Effects 0.000 description 2
• 229940088710 antibiotic agent Drugs 0.000 description 2
• 239000003080 antimitotic agent Substances 0.000 description 2
• 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• 229910052786 argon Inorganic materials 0.000 description 2
• FZCSTZYAHCUGEM-UHFFFAOYSA-N aspergillomarasmine B Natural products OC(=O)CNC(C(O)=O)CNC(C(O)=O)CC(O)=O FZCSTZYAHCUGEM-UHFFFAOYSA-N 0.000 description 2
• 229940120638 avastin Drugs 0.000 description 2
• 239000000440 bentonite Substances 0.000 description 2
• 229910000278 bentonite Inorganic materials 0.000 description 2
• 235000012216 bentonite Nutrition 0.000 description 2
• SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
• RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 2
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 2
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
• 229960000397 bevacizumab Drugs 0.000 description 2
• 208000026900 bile duct neoplasm Diseases 0.000 description 2
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 2
• 230000003115 biocidal effect Effects 0.000 description 2
• 230000004071 biological effect Effects 0.000 description 2
• IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 2
• 230000037396 body weight Effects 0.000 description 2
• 210000004556 brain Anatomy 0.000 description 2
• 230000031709 bromination Effects 0.000 description 2
• 238000005893 bromination reaction Methods 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• 229910052791 calcium Inorganic materials 0.000 description 2
• 239000011575 calcium Substances 0.000 description 2
• 235000011089 carbon dioxide Nutrition 0.000 description 2
• 239000001768 carboxy methyl cellulose Substances 0.000 description 2
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
• 208000002458 carcinoid tumor Diseases 0.000 description 2
• 210000000845 cartilage Anatomy 0.000 description 2
• 239000003153 chemical reaction reagent Substances 0.000 description 2
• 238000002512 chemotherapy Methods 0.000 description 2
• 208000006990 cholangiocarcinoma Diseases 0.000 description 2
• 210000003483 chromatin Anatomy 0.000 description 2
• 238000004587 chromatography analysis Methods 0.000 description 2
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 2
• WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 2
• 239000010779 crude oil Substances 0.000 description 2
• KVFDZFBHBWTVID-UHFFFAOYSA-N cyclohexanecarbaldehyde Chemical compound O=CC1CCCCC1 KVFDZFBHBWTVID-UHFFFAOYSA-N 0.000 description 2
• PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
• OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
• 230000001472 cytotoxic effect Effects 0.000 description 2
• 229960003603 decitabine Drugs 0.000 description 2
• 206010061428 decreased appetite Diseases 0.000 description 2
• 230000002939 deleterious effect Effects 0.000 description 2
• WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical class CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 2
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
• USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 2
• 238000004090 dissolution Methods 0.000 description 2
• 231100000371 dose-limiting toxicity Toxicity 0.000 description 2
• 239000003937 drug carrier Substances 0.000 description 2
• 238000001035 drying Methods 0.000 description 2
• 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 2
• 210000003238 esophagus Anatomy 0.000 description 2
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 2
• AUBYYJNMVKXJMI-UHFFFAOYSA-N ethyl 1-amino-6-cyclopropylpyrazolo[3,4-b]pyridine-4-carboxylate Chemical compound N=1C=2N(N)N=CC=2C(C(=O)OCC)=CC=1C1CC1 AUBYYJNMVKXJMI-UHFFFAOYSA-N 0.000 description 2
• RDBHYLHQUFLAAX-UHFFFAOYSA-N ethyl 1-cyclobutyl-6-cyclopropyl-3-methylpyrazolo[3,4-b]pyridine-4-carboxylate Chemical compound N1=C(C)C=2C(C(=O)OCC)=CC(C3CC3)=NC=2N1C1CCC1 RDBHYLHQUFLAAX-UHFFFAOYSA-N 0.000 description 2
• VEXJCJWHJAUSQZ-UHFFFAOYSA-N ethyl 1-cyclohexyl-6-cyclopropyl-3-methylpyrazolo[3,4-b]pyridine-4-carboxylate Chemical compound N1=C(C)C=2C(C(=O)OCC)=CC(C3CC3)=NC=2N1C1CCCCC1 VEXJCJWHJAUSQZ-UHFFFAOYSA-N 0.000 description 2
• YCRJQMODKMJBKW-UHFFFAOYSA-N ethyl 1-cyclopentyl-6-cyclopropyl-3-methylpyrazolo[3,4-b]pyridine-4-carboxylate Chemical compound N1=C(C)C=2C(C(=O)OCC)=CC(C3CC3)=NC=2N1C1CCCC1 YCRJQMODKMJBKW-UHFFFAOYSA-N 0.000 description 2
• DQOSKMHKJQHASI-UHFFFAOYSA-N ethyl 1-tert-butyl-6-cyclopropyl-3-methylpyrazolo[3,4-b]pyridine-4-carboxylate Chemical compound N=1C=2N(C(C)(C)C)N=C(C)C=2C(C(=O)OCC)=CC=1C1CC1 DQOSKMHKJQHASI-UHFFFAOYSA-N 0.000 description 2
• LSRYQIOKQHGSKG-UHFFFAOYSA-N ethyl 6-cyclopropyl-1-(1-cyclopropylethyl)-3-methylpyrazolo[3,4-b]pyridine-4-carboxylate Chemical compound N1=C(C)C=2C(C(=O)OCC)=CC(C3CC3)=NC=2N1C(C)C1CC1 LSRYQIOKQHGSKG-UHFFFAOYSA-N 0.000 description 2
• BTAAHXDYGAZVSW-UHFFFAOYSA-N ethyl 6-cyclopropyl-1-[(4-methoxyphenyl)methyl]pyrazolo[3,4-b]pyridine-4-carboxylate Chemical compound N1=CC=2C(C(=O)OCC)=CC(C3CC3)=NC=2N1CC1=CC=C(OC)C=C1 BTAAHXDYGAZVSW-UHFFFAOYSA-N 0.000 description 2
• JFAVBMMQIPPTHM-UHFFFAOYSA-N ethyl 6-cyclopropyl-1-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]pyrazolo[3,4-b]pyridine-4-carboxylate Chemical compound N=1C=2N(CCNC(=O)OC(C)(C)C)N=CC=2C(C(=O)OCC)=CC=1C1CC1 JFAVBMMQIPPTHM-UHFFFAOYSA-N 0.000 description 2
• SJPJNZNKMKKGHW-UHFFFAOYSA-N ethyl 6-cyclopropyl-3-methyl-1-(1-methylpiperidin-4-yl)pyrazolo[3,4-b]pyridine-4-carboxylate Chemical compound N1=C(C)C=2C(C(=O)OCC)=CC(C3CC3)=NC=2N1C1CCN(C)CC1 SJPJNZNKMKKGHW-UHFFFAOYSA-N 0.000 description 2
• UUZKTLHDAWGMFQ-UHFFFAOYSA-N ethyl 6-cyclopropyl-3-methyl-1-(oxan-4-yl)pyrazolo[3,4-b]pyridine-4-carboxylate Chemical compound N1=C(C)C=2C(C(=O)OCC)=CC(C3CC3)=NC=2N1C1CCOCC1 UUZKTLHDAWGMFQ-UHFFFAOYSA-N 0.000 description 2
• ZBMBTJYAHVBSHF-UHFFFAOYSA-N ethyl 6-cyclopropyl-3-methyl-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxylate Chemical compound N=1C=2N(C(C)C)N=C(C)C=2C(C(=O)OCC)=CC=1C1CC1 ZBMBTJYAHVBSHF-UHFFFAOYSA-N 0.000 description 2
• BUVLXUFHIMMIPM-UHFFFAOYSA-N ethyl 6-cyclopropyl-3-methyl-1-pyridin-4-ylpyrazolo[3,4-b]pyridine-4-carboxylate Chemical compound N1=C(C)C=2C(C(=O)OCC)=CC(C3CC3)=NC=2N1C1=CC=NC=C1 BUVLXUFHIMMIPM-UHFFFAOYSA-N 0.000 description 2
• 125000004494 ethyl ester group Chemical group 0.000 description 2
• 239000000835 fiber Substances 0.000 description 2
• 238000011049 filling Methods 0.000 description 2
• 239000006260 foam Substances 0.000 description 2
• 239000007789 gas Substances 0.000 description 2
• 230000002496 gastric effect Effects 0.000 description 2
• 208000018925 gastrointestinal mucositis Diseases 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 125000001188 haloalkyl group Chemical group 0.000 description 2
• 239000003276 histone deacetylase inhibitor Substances 0.000 description 2
• 239000002944 hormone and hormone analog Substances 0.000 description 2
• 150000004677 hydrates Chemical class 0.000 description 2
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
• 150000002430 hydrocarbons Chemical group 0.000 description 2
• 150000003840 hydrochlorides Chemical class 0.000 description 2
• YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.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 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 description 2
• 230000009545 invasion Effects 0.000 description 2
• TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
• 210000003734 kidney Anatomy 0.000 description 2
• 201000010260 leiomyoma Diseases 0.000 description 2
• 239000003446 ligand Substances 0.000 description 2
• 229910052744 lithium Inorganic materials 0.000 description 2
• 210000004185 liver Anatomy 0.000 description 2
• 229910052749 magnesium Inorganic materials 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
• 235000019341 magnesium sulphate Nutrition 0.000 description 2
• 238000004949 mass spectrometry Methods 0.000 description 2
• 206010027191 meningioma Diseases 0.000 description 2
• 229910052751 metal Inorganic materials 0.000 description 2
• 239000002184 metal Substances 0.000 description 2
• 230000009401 metastasis Effects 0.000 description 2
• 230000001394 metastastic effect Effects 0.000 description 2
• 206010061289 metastatic neoplasm Diseases 0.000 description 2
• QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
• 210000004688 microtubule Anatomy 0.000 description 2
• 238000002156 mixing Methods 0.000 description 2
• 230000035772 mutation Effects 0.000 description 2
• 150000002825 nitriles Chemical class 0.000 description 2
• 239000012299 nitrogen atmosphere Substances 0.000 description 2
• 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• 150000007523 nucleic acids Chemical group 0.000 description 2
• 210000001623 nucleosome Anatomy 0.000 description 2
• ZWLPBLYKEWSWPD-UHFFFAOYSA-N o-toluic acid Chemical compound CC1=CC=CC=C1C(O)=O ZWLPBLYKEWSWPD-UHFFFAOYSA-N 0.000 description 2
• 239000012074 organic phase Substances 0.000 description 2
• 230000002611 ovarian Effects 0.000 description 2
• 210000001672 ovary Anatomy 0.000 description 2
• WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 2
• CMXVPHSHKFQSHM-UHFFFAOYSA-N oxan-4-ylhydrazine Chemical compound NNC1CCOCC1 CMXVPHSHKFQSHM-UHFFFAOYSA-N 0.000 description 2
• MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 2
• 238000010651 palladium-catalyzed cross coupling reaction Methods 0.000 description 2
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
• 210000000496 pancreas Anatomy 0.000 description 2
• 230000007918 pathogenicity Effects 0.000 description 2
• 239000003208 petroleum Substances 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
• 239000010452 phosphate Substances 0.000 description 2
• 229910003446 platinum oxide Inorganic materials 0.000 description 2
• 125000003367 polycyclic group Chemical group 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• 235000011056 potassium acetate Nutrition 0.000 description 2
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
• 230000035755 proliferation Effects 0.000 description 2
• KJAQRHMKLVGSCG-UHFFFAOYSA-N propan-2-ylhydrazine Chemical compound CC(C)NN KJAQRHMKLVGSCG-UHFFFAOYSA-N 0.000 description 2
• 108060006633 protein kinase Proteins 0.000 description 2
• 102000004169 proteins and genes Human genes 0.000 description 2
• 150000003212 purines Chemical class 0.000 description 2
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 2
• TXQWFIVRZNOPCK-UHFFFAOYSA-N pyridin-4-ylmethanamine Chemical compound NCC1=CC=NC=C1 TXQWFIVRZNOPCK-UHFFFAOYSA-N 0.000 description 2
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 2
• 238000001959 radiotherapy Methods 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 230000010076 replication Effects 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 125000006413 ring segment Chemical group 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 2
• 210000003491 skin Anatomy 0.000 description 2
• 238000009491 slugging Methods 0.000 description 2
• 150000003384 small molecules Chemical class 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• 239000012312 sodium hydride Substances 0.000 description 2
• 229910000104 sodium hydride Inorganic materials 0.000 description 2
• 239000008107 starch Substances 0.000 description 2
• 235000019698 starch Nutrition 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• 230000000707 stereoselective effect Effects 0.000 description 2
• 235000000346 sugar Nutrition 0.000 description 2
• 238000001356 surgical procedure Methods 0.000 description 2
• 230000002194 synthesizing effect Effects 0.000 description 2
• 238000010189 synthetic method Methods 0.000 description 2
• 239000006188 syrup Substances 0.000 description 2
• 235000020357 syrup Nutrition 0.000 description 2
• 239000000454 talc Substances 0.000 description 2
• 229910052623 talc Inorganic materials 0.000 description 2
• 235000012222 talc Nutrition 0.000 description 2
• KBMQRTAUUQMJGF-UHFFFAOYSA-N tert-butyl n-(oxan-4-ylamino)carbamate Chemical compound CC(C)(C)OC(=O)NNC1CCOCC1 KBMQRTAUUQMJGF-UHFFFAOYSA-N 0.000 description 2
• VTZLKGHELSHARD-UHFFFAOYSA-N tert-butyl n-[(6-cyclopropyl-4-methyl-2-oxo-1h-pyridin-3-yl)methyl]carbamate Chemical compound N1C(=O)C(CNC(=O)OC(C)(C)C)=C(C)C=C1C1CC1 VTZLKGHELSHARD-UHFFFAOYSA-N 0.000 description 2
• 150000003536 tetrazoles Chemical class 0.000 description 2
• 229940124597 therapeutic agent Drugs 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 2
• 238000004809 thin layer chromatography Methods 0.000 description 2
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
• 229930192474 thiophene Natural products 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
• 150000004654 triazenes Chemical class 0.000 description 2
• 150000003852 triazoles Chemical class 0.000 description 2
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
• 210000004881 tumor cell Anatomy 0.000 description 2
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 2
• 210000003932 urinary bladder Anatomy 0.000 description 2
• 238000003828 vacuum filtration Methods 0.000 description 2
• GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 2
• 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
• PVEJOCQTIVCDNO-UHFFFAOYSA-N (2,4-dioxo-1h-pyrimidin-5-yl)boronic acid Chemical compound OB(O)C1=CNC(=O)NC1=O PVEJOCQTIVCDNO-UHFFFAOYSA-N 0.000 description 1
• NSJVYHOPHZMZPN-UHFFFAOYSA-N (2-methylphenyl)boronic acid Chemical compound CC1=CC=CC=C1B(O)O NSJVYHOPHZMZPN-UHFFFAOYSA-N 0.000 description 1
• RGHNJXZEOKUKBD-NRXMZTRTSA-N (2r,3r,4r,5s)-2,3,4,5,6-pentahydroxyhexanoic acid Chemical compound OC[C@H](O)[C@@H](O)[C@@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-NRXMZTRTSA-N 0.000 description 1
• JNSWIYCWZPFQQF-JGVFFNPUSA-N (2r,3s)-3-(carboxyamino)-2-hydroxy-3-phenylpropanoic acid Chemical compound OC(=O)[C@H](O)[C@@H](NC(O)=O)C1=CC=CC=C1 JNSWIYCWZPFQQF-JGVFFNPUSA-N 0.000 description 1
• HYJVYOWKYPNSTK-UONOGXRCSA-N (2r,3s)-3-benzamido-2-hydroxy-3-phenylpropanoic acid Chemical compound N([C@H]([C@@H](O)C(O)=O)C=1C=CC=CC=1)C(=O)C1=CC=CC=C1 HYJVYOWKYPNSTK-UONOGXRCSA-N 0.000 description 1
• IBTSWKLSEOGJGJ-UHFFFAOYSA-N (3-acetamidophenyl)boronic acid Chemical compound CC(=O)NC1=CC=CC(B(O)O)=C1 IBTSWKLSEOGJGJ-UHFFFAOYSA-N 0.000 description 1
• YVNOLHVCLKCHOC-UHFFFAOYSA-N (4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl 6-cyclopropyl-1-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]pyrazolo[3,4-b]pyridine-4-carboxylate Chemical compound O=C1NC(C)=CC(C)=C1COC(=O)C1=CC(C2CC2)=NC2=C1C=NN2CCNC(=O)OC(C)(C)C YVNOLHVCLKCHOC-UHFFFAOYSA-N 0.000 description 1
• MKPDAJWEBQRQCO-UHFFFAOYSA-N (4-aminophenyl)boronic acid Chemical compound NC1=CC=C(B(O)O)C=C1 MKPDAJWEBQRQCO-UHFFFAOYSA-N 0.000 description 1
• GNRHNKBJNUVWFZ-UHFFFAOYSA-N (4-carbamoylphenyl)boronic acid Chemical compound NC(=O)C1=CC=C(B(O)O)C=C1 GNRHNKBJNUVWFZ-UHFFFAOYSA-N 0.000 description 1
• AKSXQPCIAOIJGP-UHFFFAOYSA-N (4-sulfamoylphenyl)boronic acid Chemical compound NS(=O)(=O)C1=CC=C(B(O)O)C=C1 AKSXQPCIAOIJGP-UHFFFAOYSA-N 0.000 description 1
• YGXNPQDXWDCWET-UHFFFAOYSA-N (5-methylsulfonylpyridin-3-yl)boronic acid Chemical compound CS(=O)(=O)C1=CN=CC(B(O)O)=C1 YGXNPQDXWDCWET-UHFFFAOYSA-N 0.000 description 1
• DHADXDMPEUWEAS-UHFFFAOYSA-N (6-methoxypyridin-3-yl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=N1 DHADXDMPEUWEAS-UHFFFAOYSA-N 0.000 description 1
• FPVKHBSQESCIEP-UHFFFAOYSA-N (8S)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol Natural products C1C(O)C(CO)OC1N1C(NC=NCC2O)=C2N=C1 FPVKHBSQESCIEP-UHFFFAOYSA-N 0.000 description 1
• UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
• IYMKNYVCXUEFJE-SNAWJCMRSA-N (e)-5-methylhex-3-en-2-one Chemical compound CC(C)\C=C\C(C)=O IYMKNYVCXUEFJE-SNAWJCMRSA-N 0.000 description 1
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
• CSVFWMMPUJDVKH-UHFFFAOYSA-N 1,1-dichloropropan-2-one Chemical compound CC(=O)C(Cl)Cl CSVFWMMPUJDVKH-UHFFFAOYSA-N 0.000 description 1
• QACMXJJLQXUOPQ-UHFFFAOYSA-N 1,2-dichloroethane;3-(ethyliminomethylideneamino)-n,n-dimethylpropan-1-amine Chemical compound ClCCCl.CCN=C=NCCCN(C)C QACMXJJLQXUOPQ-UHFFFAOYSA-N 0.000 description 1
• DMECABOZAOLLJG-UHFFFAOYSA-N 1,6-di(propan-2-yl)pyrazolo[3,4-b]pyridine-4-carboxylic acid Chemical compound CC(C)C1=CC(C(O)=O)=C2C=NN(C(C)C)C2=N1 DMECABOZAOLLJG-UHFFFAOYSA-N 0.000 description 1
• ZPVOFDSZWZKZJS-UHFFFAOYSA-N 1-amino-6-cyclopropyl-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]pyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound O=C1NC(C)=CC(C)=C1CNC(=O)C1=CC(C2CC2)=NC2=C1C=NN2N ZPVOFDSZWZKZJS-UHFFFAOYSA-N 0.000 description 1
• HKIIDGKOOZXNQC-UHFFFAOYSA-N 1-benzylpyrazol-4-amine Chemical compound C1=C(N)C=NN1CC1=CC=CC=C1 HKIIDGKOOZXNQC-UHFFFAOYSA-N 0.000 description 1
• HNAGHMKIPMKKBB-UHFFFAOYSA-N 1-benzylpyrrolidine-3-carboxamide Chemical compound C1C(C(=O)N)CCN1CC1=CC=CC=C1 HNAGHMKIPMKKBB-UHFFFAOYSA-N 0.000 description 1
• IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
• RDFJBDMCBVSCFI-UHFFFAOYSA-N 1-methyl-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]piperazine Chemical compound C1CN(C)CCN1C1=CC=C(B2OC(C)(C)C(C)(C)O2)C=C1 RDFJBDMCBVSCFI-UHFFFAOYSA-N 0.000 description 1
• OVNWRUULQMZZNB-UHFFFAOYSA-N 1-methyl-4-phenylpyridin-2-one Chemical compound O=C1N(C)C=CC(C=2C=CC=CC=2)=C1 OVNWRUULQMZZNB-UHFFFAOYSA-N 0.000 description 1
• TZTXTIBZSSSFDI-UHFFFAOYSA-N 1-pyridin-2-ylpropan-2-one Chemical compound CC(=O)CC1=CC=CC=N1 TZTXTIBZSSSFDI-UHFFFAOYSA-N 0.000 description 1
• WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical class CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 1
• 238000005160 1H NMR spectroscopy Methods 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-L 2,3-dihydroxybutanedioate Chemical compound [O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-L 0.000 description 1
• HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
• WWUFXXHXBBRKJV-UHFFFAOYSA-N 2-(1-cyclopropylethyl)-5-methylpyrazol-3-amine Chemical compound N1=C(C)C=C(N)N1C(C)C1CC1 WWUFXXHXBBRKJV-UHFFFAOYSA-N 0.000 description 1
• GWEWQKZABZXLJH-UHFFFAOYSA-N 2-(furan-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=CO1 GWEWQKZABZXLJH-UHFFFAOYSA-N 0.000 description 1
• CJDYNUBRSBSSJU-UHFFFAOYSA-N 2-benzylpyrazol-3-amine Chemical compound NC1=CC=NN1CC1=CC=CC=C1 CJDYNUBRSBSSJU-UHFFFAOYSA-N 0.000 description 1
• 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 1
• QCFRHISLUKNFQV-UHFFFAOYSA-N 2-cyclohexyl-5-methylpyrazol-3-amine Chemical compound N1=C(C)C=C(N)N1C1CCCCC1 QCFRHISLUKNFQV-UHFFFAOYSA-N 0.000 description 1
• RLHAGSICYJAHMN-UHFFFAOYSA-N 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine Chemical compound C1=NC(OC)=CC(B2OC(C)(C)C(C)(C)O2)=C1 RLHAGSICYJAHMN-UHFFFAOYSA-N 0.000 description 1
• CEBKHWWANWSNTI-UHFFFAOYSA-N 2-methylbut-3-yn-2-ol Chemical compound CC(C)(O)C#C CEBKHWWANWSNTI-UHFFFAOYSA-N 0.000 description 1
• SDTMFDGELKWGFT-UHFFFAOYSA-N 2-methylpropan-2-olate Chemical compound CC(C)(C)[O-] SDTMFDGELKWGFT-UHFFFAOYSA-N 0.000 description 1
• FXWWSHVAIPUGQM-UHFFFAOYSA-N 2h-benzotriazol-5-ylboronic acid Chemical compound C1=C(B(O)O)C=CC2=NNN=C21 FXWWSHVAIPUGQM-UHFFFAOYSA-N 0.000 description 1
• ZZVDXRCAGGQFAK-UHFFFAOYSA-N 2h-oxazaphosphinine Chemical class N1OC=CC=P1 ZZVDXRCAGGQFAK-UHFFFAOYSA-N 0.000 description 1
• ZMDPNGUJHPRAMG-UHFFFAOYSA-N 3-(aminomethyl)-4,6-dimethyl-1h-pyridin-2-one;hydrochloride Chemical compound Cl.CC1=CC(C)=C(CN)C(=O)N1 ZMDPNGUJHPRAMG-UHFFFAOYSA-N 0.000 description 1
• PBGAZQLIFHVHCX-UHFFFAOYSA-N 3-(aminomethyl)-4-cyclohexyl-6-methyl-1h-pyridin-2-one Chemical compound O=C1NC(C)=CC(C2CCCCC2)=C1CN PBGAZQLIFHVHCX-UHFFFAOYSA-N 0.000 description 1
• NBCTZIZRDMGIPQ-UHFFFAOYSA-N 3-(aminomethyl)-4-cyclopropyl-6-methyl-1h-pyridin-2-one Chemical compound O=C1NC(C)=CC(C2CC2)=C1CN NBCTZIZRDMGIPQ-UHFFFAOYSA-N 0.000 description 1
• BAVXDKPOILXFMA-UHFFFAOYSA-N 3-(aminomethyl)-4-cyclopropyl-6-methyl-1h-pyridin-2-one;hydrochloride Chemical compound Cl.O=C1NC(C)=CC(C2CC2)=C1CN BAVXDKPOILXFMA-UHFFFAOYSA-N 0.000 description 1
• GUKYWJUKCYHNAQ-UHFFFAOYSA-N 3-(aminomethyl)-4-methyl-6-propyl-1h-pyridin-2-one;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCCC1=CC(C)=C(CN)C(=O)N1 GUKYWJUKCYHNAQ-UHFFFAOYSA-N 0.000 description 1
• NSVQBSIXBBDJTB-UHFFFAOYSA-N 3-(aminomethyl)-5-fluoro-4,6-dimethyl-1h-pyridin-2-one;hydrochloride Chemical compound Cl.CC=1NC(=O)C(CN)=C(C)C=1F NSVQBSIXBBDJTB-UHFFFAOYSA-N 0.000 description 1
• AWQYPAVOIYFYRY-UHFFFAOYSA-N 3-(aminomethyl)-6-cyclopropyl-4-methyl-1h-pyridin-2-one Chemical compound N1C(=O)C(CN)=C(C)C=C1C1CC1 AWQYPAVOIYFYRY-UHFFFAOYSA-N 0.000 description 1
• SAGQDADZYGKKAO-UHFFFAOYSA-N 3-(aminomethyl)-6-ethyl-4-methyl-1h-pyridin-2-one Chemical compound CCC1=CC(C)=C(CN)C(=O)N1 SAGQDADZYGKKAO-UHFFFAOYSA-N 0.000 description 1
• DOWZZENLBJUPCR-UHFFFAOYSA-N 3-(aminomethyl)-6-methyl-4-phenyl-1h-pyridin-2-one Chemical compound O=C1NC(C)=CC(C=2C=CC=CC=2)=C1CN DOWZZENLBJUPCR-UHFFFAOYSA-N 0.000 description 1
• JHHZQADGLDKIPM-AATRIKPKSA-N 3-Hepten-2-one Chemical compound CCC\C=C\C(C)=O JHHZQADGLDKIPM-AATRIKPKSA-N 0.000 description 1
• OMKHWTRUYNAGFG-IEBDPFPHSA-N 3-deazaneplanocin a Chemical compound C1=NC=2C(N)=NC=CC=2N1[C@@H]1C=C(CO)[C@@H](O)[C@H]1O OMKHWTRUYNAGFG-IEBDPFPHSA-N 0.000 description 1
• RRRCPCOJPQLWEP-UHFFFAOYSA-N 3-hydroxytriazolo[4,5-b]pyridine Chemical compound C1=CN=C2N(O)N=NC2=C1.C1=CN=C2N(O)N=NC2=C1 RRRCPCOJPQLWEP-UHFFFAOYSA-N 0.000 description 1
• HENXUFOAGXNWKH-UHFFFAOYSA-N 3-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine Chemical compound COC1=CN=CC(B2OC(C)(C)C(C)(C)O2)=C1 HENXUFOAGXNWKH-UHFFFAOYSA-N 0.000 description 1
• OCYMJCILWYHKAU-UHFFFAOYSA-N 4,6-dimethyl-2-oxo-1h-pyridine-3-carbonitrile Chemical compound CC1=CC(C)=C(C#N)C(O)=N1 OCYMJCILWYHKAU-UHFFFAOYSA-N 0.000 description 1
• TVOJIBGZFYMWDT-UHFFFAOYSA-N 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1h-pyrazole Chemical compound O1C(C)(C)C(C)(C)OB1C1=CNN=C1 TVOJIBGZFYMWDT-UHFFFAOYSA-N 0.000 description 1
• DCYKWKYBNWRLLZ-UHFFFAOYSA-N 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=NC(N)=C1 DCYKWKYBNWRLLZ-UHFFFAOYSA-N 0.000 description 1
• QIKYZXDTTPVVAC-UHFFFAOYSA-N 4-Aminobenzamide Chemical compound NC(=O)C1=CC=C(N)C=C1 QIKYZXDTTPVVAC-UHFFFAOYSA-N 0.000 description 1
• XXJWYDDUDKYVKI-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(1-pyrrolidinyl)propoxy]quinazoline Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)N=CN=C2C=C1OCCCN1CCCC1 XXJWYDDUDKYVKI-UHFFFAOYSA-N 0.000 description 1
• HZJIGVGLNZISJU-UHFFFAOYSA-N 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]morpholine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=NC(N2CCOCC2)=C1 HZJIGVGLNZISJU-UHFFFAOYSA-N 0.000 description 1
• HVBSAKJJOYLTQU-UHFFFAOYSA-M 4-aminobenzenesulfonate Chemical compound NC1=CC=C(S([O-])(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-M 0.000 description 1
• NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 1
• WUBBRNOQWQTFEX-UHFFFAOYSA-M 4-aminosalicylate(1-) Chemical compound NC1=CC=C(C([O-])=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-M 0.000 description 1
• PLNLUZYSEVYBIK-UHFFFAOYSA-N 4-cyclohexyl-6-methyl-2-oxo-1h-pyridine-3-carbonitrile Chemical compound O=C1NC(C)=CC(C2CCCCC2)=C1C#N PLNLUZYSEVYBIK-UHFFFAOYSA-N 0.000 description 1
• PQYDGUICOMJCLY-UHFFFAOYSA-N 4-cyclopropyl-6-methyl-2-oxo-1h-pyridine-3-carbonitrile Chemical compound O=C1NC(C)=CC(C2CC2)=C1C#N PQYDGUICOMJCLY-UHFFFAOYSA-N 0.000 description 1
• FDEDJRHULYIJOR-UHFFFAOYSA-N 4-ethynylpyridine Chemical compound C#CC1=CC=NC=C1 FDEDJRHULYIJOR-UHFFFAOYSA-N 0.000 description 1
• LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 1
• BNNMDMGPZUOOOE-UHFFFAOYSA-N 4-methylbenzenesulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1.CC1=CC=C(S(O)(=O)=O)C=C1 BNNMDMGPZUOOOE-UHFFFAOYSA-N 0.000 description 1
• BXFPTCYBFJOZHJ-UHFFFAOYSA-N 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dihydroindol-2-one Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(NC(=O)C2)C2=C1 BXFPTCYBFJOZHJ-UHFFFAOYSA-N 0.000 description 1
• SAGPUUKLGWNGOS-UHFFFAOYSA-N 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1h-indazole Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(NN=C2)C2=C1 SAGPUUKLGWNGOS-UHFFFAOYSA-N 0.000 description 1
• YFTAUNOLAHRUIE-UHFFFAOYSA-N 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(N)N=C1 YFTAUNOLAHRUIE-UHFFFAOYSA-N 0.000 description 1
• BPQVMIDUTRJYSC-UHFFFAOYSA-N 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CN=C(N)N=C1 BPQVMIDUTRJYSC-UHFFFAOYSA-N 0.000 description 1
• NMUSYJAQQFHJEW-UHFFFAOYSA-N 5-Azacytidine Natural products O=C1N=C(N)N=CN1C1C(O)C(O)C(CO)O1 NMUSYJAQQFHJEW-UHFFFAOYSA-N 0.000 description 1
• BCXSVFBDMPSKPT-UHFFFAOYSA-N 5-amino-1,3-dihydrobenzimidazol-2-one Chemical compound NC1=CC=C2NC(=O)NC2=C1 BCXSVFBDMPSKPT-UHFFFAOYSA-N 0.000 description 1
• IAJRTGABDFKUSX-UHFFFAOYSA-N 5-amino-1-propan-2-ylpyrazole-4-carboxylic acid Chemical compound CC(C)N1N=CC(C(O)=O)=C1N IAJRTGABDFKUSX-UHFFFAOYSA-N 0.000 description 1
• CZPJXSLJOVFCOH-UHFFFAOYSA-N 5-bromopyridine-2-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=C(Br)C=N1 CZPJXSLJOVFCOH-UHFFFAOYSA-N 0.000 description 1
• HFEKDTCAMMOLQP-RRKCRQDMSA-N 5-fluorodeoxyuridine monophosphate Chemical compound O1[C@H](COP(O)(O)=O)[C@@H](O)C[C@@H]1N1C(=O)NC(=O)C(F)=C1 HFEKDTCAMMOLQP-RRKCRQDMSA-N 0.000 description 1
• NNBQKNVCHRPVFE-UHFFFAOYSA-N 5-methyl-2-(1-methylpiperidin-4-yl)pyrazol-3-amine Chemical compound C1CN(C)CCC1N1C(N)=CC(C)=N1 NNBQKNVCHRPVFE-UHFFFAOYSA-N 0.000 description 1
• YKVBZKPLBUPJCX-UHFFFAOYSA-N 5-methyl-2-pyridin-4-ylpyrazol-3-amine Chemical compound N1=C(C)C=C(N)N1C1=CC=NC=C1 YKVBZKPLBUPJCX-UHFFFAOYSA-N 0.000 description 1
• RGBUBXPAZXBNMI-UHFFFAOYSA-N 6,8,11-trihydroxy-1-methoxy-7,8,9,10-tetrahydrotetracene-5,12-dione;hydrochloride Chemical compound Cl.C1C(O)CCC2=C1C(O)=C1C(=O)C(C=CC=C3OC)=C3C(=O)C1=C2O RGBUBXPAZXBNMI-UHFFFAOYSA-N 0.000 description 1
• NXJYMGPXHVQNOT-UHFFFAOYSA-N 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-dihydroindol-2-one Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(CC(=O)N2)C2=C1 NXJYMGPXHVQNOT-UHFFFAOYSA-N 0.000 description 1
• YDWZPHAJTNZBEG-UHFFFAOYSA-N 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1h-indazole Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(C=NN2)C2=C1 YDWZPHAJTNZBEG-UHFFFAOYSA-N 0.000 description 1
• OXYLZYCQFHCRDZ-UHFFFAOYSA-N 6-(benzylamino)-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1NCC1=CC=CC=C1 OXYLZYCQFHCRDZ-UHFFFAOYSA-N 0.000 description 1
• HVKVYHKBDPYCHS-UHFFFAOYSA-N 6-(dimethylamino)-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=C(N(C)C)N=C2N(C(C)C)N=CC2=C1C(=O)NCC1=C(C)C=C(C)NC1=O HVKVYHKBDPYCHS-UHFFFAOYSA-N 0.000 description 1
• VJEOGGNIBLORIJ-UHFFFAOYSA-N 6-bromo-3,4-dihydro-1h-1,8-naphthyridin-2-one Chemical compound N1C(=O)CCC2=CC(Br)=CN=C21 VJEOGGNIBLORIJ-UHFFFAOYSA-N 0.000 description 1
• RRKFTXYUERYMAB-UHFFFAOYSA-N 6-cyclopropyl-1-(2-methylpropyl)pyrazolo[3,4-b]pyridine-4-carboxylic acid Chemical compound N1=C2N(CC(C)C)N=CC2=C(C(O)=O)C=C1C1CC1 RRKFTXYUERYMAB-UHFFFAOYSA-N 0.000 description 1
• FZWKPTLDPKVNRS-UHFFFAOYSA-N 6-cyclopropyl-3-methyl-1-(oxan-4-yl)pyrazolo[3,4-b]pyridine-4-carboxylic acid Chemical compound C12=NC(C3CC3)=CC(C(O)=O)=C2C(C)=NN1C1CCOCC1 FZWKPTLDPKVNRS-UHFFFAOYSA-N 0.000 description 1
• MASWFOBXAQJQRZ-UHFFFAOYSA-N 6-cyclopropyl-3-methyl-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxylic acid Chemical compound N1=C2N(C(C)C)N=C(C)C2=C(C(O)=O)C=C1C1CC1 MASWFOBXAQJQRZ-UHFFFAOYSA-N 0.000 description 1
• FZTBEHSMFGKXNA-UHFFFAOYSA-N 6-methyl-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxylic acid Chemical compound C1=C(C)N=C2N(C(C)C)N=CC2=C1C(O)=O FZTBEHSMFGKXNA-UHFFFAOYSA-N 0.000 description 1
• IMPQPQKUDMOZHV-UHFFFAOYSA-N 6-methyl-2-oxo-4-(trifluoromethyl)-1H-pyridine-3-carbonitrile Chemical compound CC1=CC(C(F)(F)F)=C(C#N)C(=O)N1 IMPQPQKUDMOZHV-UHFFFAOYSA-N 0.000 description 1
• FVWHXCPGGVRTCS-UHFFFAOYSA-N 6-phenyl-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxylic acid Chemical compound N1=C2N(C(C)C)N=CC2=C(C(O)=O)C=C1C1=CC=CC=C1 FVWHXCPGGVRTCS-UHFFFAOYSA-N 0.000 description 1
• FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-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
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
• 229930024421 Adenine Natural products 0.000 description 1
• GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
• 102000005234 Adenosylhomocysteinase Human genes 0.000 description 1
• 108020002202 Adenosylhomocysteinase Proteins 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
• 239000005695 Ammonium acetate Substances 0.000 description 1
• 102100022014 Angiopoietin-1 receptor Human genes 0.000 description 1
• 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
• 108091023037 Aptamer Proteins 0.000 description 1
• BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• 206010003571 Astrocytoma Diseases 0.000 description 1
• 208000023275 Autoimmune disease Diseases 0.000 description 1
• MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 description 1
• 206010004146 Basal cell carcinoma Diseases 0.000 description 1
• BWHOZHOGCMHOBV-UHFFFAOYSA-N Benzalacetone Natural products CC(=O)C=CC1=CC=CC=C1 BWHOZHOGCMHOBV-UHFFFAOYSA-N 0.000 description 1
• KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 1
• GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
• 206010073106 Bone giant cell tumour malignant Diseases 0.000 description 1
• 239000004135 Bone phosphate Substances 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
• PCBZRNYXXCIELG-WYFCWLEVSA-N COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 Chemical compound COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 PCBZRNYXXCIELG-WYFCWLEVSA-N 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 208000009458 Carcinoma in Situ Diseases 0.000 description 1
• 206010008263 Cervical dysplasia Diseases 0.000 description 1
• 206010008342 Cervix carcinoma Diseases 0.000 description 1
• 201000005262 Chondroma Diseases 0.000 description 1
• 208000005243 Chondrosarcoma Diseases 0.000 description 1
• 201000009047 Chordoma Diseases 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
• PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 description 1
• 238000003512 Claisen condensation reaction Methods 0.000 description 1
• 206010048832 Colon adenoma Diseases 0.000 description 1
• 206010010356 Congenital anomaly Diseases 0.000 description 1
• 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
• 231100001074 DNA strand break Toxicity 0.000 description 1
• GUGHGUXZJWAIAS-QQYBVWGSSA-N Daunorubicin hydrochloride Chemical compound Cl.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(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 GUGHGUXZJWAIAS-QQYBVWGSSA-N 0.000 description 1
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-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
• 206010012735 Diarrhoea Diseases 0.000 description 1
• MWWSFMDVAYGXBV-RUELKSSGSA-N Doxorubicin hydrochloride Chemical compound Cl.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 MWWSFMDVAYGXBV-RUELKSSGSA-N 0.000 description 1
• 208000000471 Dysplastic Nevus Syndrome Diseases 0.000 description 1
• 102000001301 EGF receptor Human genes 0.000 description 1
• 108060006698 EGF receptor Proteins 0.000 description 1
• 241000257465 Echinoidea Species 0.000 description 1
• 201000009051 Embryonal Carcinoma Diseases 0.000 description 1
• 206010014733 Endometrial cancer Diseases 0.000 description 1
• 206010014759 Endometrial neoplasm Diseases 0.000 description 1
• 241000792859 Enema Species 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 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
• 208000022072 Gallbladder Neoplasms Diseases 0.000 description 1
• 208000000527 Germinoma Diseases 0.000 description 1
• 208000007569 Giant Cell Tumors Diseases 0.000 description 1
• 206010018404 Glucagonoma Diseases 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• 206010018691 Granuloma Diseases 0.000 description 1
• 208000002927 Hamartoma Diseases 0.000 description 1
• 206010019629 Hepatic adenoma Diseases 0.000 description 1
• 101000753291 Homo sapiens Angiopoietin-1 receptor Proteins 0.000 description 1
• 101100389970 Homo sapiens EZH2 gene Proteins 0.000 description 1
• 101000615488 Homo sapiens Methyl-CpG-binding domain protein 2 Proteins 0.000 description 1
• 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 1
• 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
• 206010062904 Hormone-refractory prostate cancer Diseases 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• 229940124036 Hydrolase inhibitor Drugs 0.000 description 1
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
• 208000002260 Keloid Diseases 0.000 description 1
• 206010023330 Keloid scar Diseases 0.000 description 1
• 229930194542 Keto Natural products 0.000 description 1
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
• 239000005517 L01XE01 - Imatinib Substances 0.000 description 1
• 239000002147 L01XE04 - Sunitinib Substances 0.000 description 1
• 239000005511 L01XE05 - Sorafenib Substances 0.000 description 1
• 239000003798 L01XE11 - Pazopanib Substances 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 1
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• 208000035561 Leukaemic infiltration brain Diseases 0.000 description 1
• 208000002404 Liver Cell Adenoma Diseases 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 208000006644 Malignant Fibrous Histiocytoma Diseases 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 208000000172 Medulloblastoma Diseases 0.000 description 1
• 206010027480 Metastatic malignant melanoma Diseases 0.000 description 1
• 241001465754 Metazoa Species 0.000 description 1
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
• 102100021299 Methyl-CpG-binding domain protein 2 Human genes 0.000 description 1
• 108060004795 Methyltransferase Proteins 0.000 description 1
• 102000016397 Methyltransferase Human genes 0.000 description 1
• 208000031888 Mycoses Diseases 0.000 description 1
• 208000014767 Myeloproliferative disease Diseases 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• 239000007832 Na2SO4 Substances 0.000 description 1
• 206010029155 Nephropathy toxic Diseases 0.000 description 1
• 206010029260 Neuroblastoma Diseases 0.000 description 1
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
• WNFDIHZFFFOZBP-OPWCVFCNSA-N O1C(=CC=C1)O[C@@]1([C@H](O)[C@H](O)[C@@H](CO)O1)N1C(=O)NC(=O)C=C1.FC=1C(NC(N([C@H]2C[C@H](O)[C@@H](CO)O2)C1)=O)=O Chemical compound O1C(=CC=C1)O[C@@]1([C@H](O)[C@H](O)[C@@H](CO)O1)N1C(=O)NC(=O)C=C1.FC=1C(NC(N([C@H]2C[C@H](O)[C@@H](CO)O2)C1)=O)=O WNFDIHZFFFOZBP-OPWCVFCNSA-N 0.000 description 1
• 201000010133 Oligodendroglioma Diseases 0.000 description 1
• 108700020796 Oncogene Proteins 0.000 description 1
• 102000043276 Oncogene Human genes 0.000 description 1
• 235000019502 Orange oil Nutrition 0.000 description 1
• 206010033109 Ototoxicity Diseases 0.000 description 1
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
• 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 1
• 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 1
• 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 1
• 244000236480 Podophyllum peltatum Species 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• 208000004880 Polyuria Diseases 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
• 201000004681 Psoriasis Diseases 0.000 description 1
• 206010061924 Pulmonary toxicity Diseases 0.000 description 1
• 208000015634 Rectal Neoplasms Diseases 0.000 description 1
• 201000000582 Retinoblastoma Diseases 0.000 description 1
• 102000014400 SH2 domains Human genes 0.000 description 1
• 108050003452 SH2 domains Proteins 0.000 description 1
• 102000000395 SH3 domains Human genes 0.000 description 1
• 108050008861 SH3 domains Proteins 0.000 description 1
• 206010039491 Sarcoma Diseases 0.000 description 1
• 229940124639 Selective inhibitor Drugs 0.000 description 1
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
• 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
• 208000000097 Sertoli-Leydig cell tumor Diseases 0.000 description 1
• 229920001800 Shellac Polymers 0.000 description 1
• 229910004298 SiO 2 Inorganic materials 0.000 description 1
• 208000000453 Skin Neoplasms Diseases 0.000 description 1
• 206010059516 Skin toxicity Diseases 0.000 description 1
• 206010041067 Small cell lung cancer Diseases 0.000 description 1
• 108091027967 Small hairpin RNA Proteins 0.000 description 1
• 108020004459 Small interfering RNA Proteins 0.000 description 1
• BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 241001147844 Streptomyces verticillus Species 0.000 description 1
• 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 description 1
• 229920002253 Tannate Polymers 0.000 description 1
• 229940123237 Taxane Drugs 0.000 description 1
• 241000202349 Taxus brevifolia Species 0.000 description 1
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
• 239000004473 Threonine Substances 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• 108091023040 Transcription factor Proteins 0.000 description 1
• 102000040945 Transcription factor Human genes 0.000 description 1
• 206010052779 Transplant rejections Diseases 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 1
• 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 1
• 208000015778 Undifferentiated pleomorphic sarcoma Diseases 0.000 description 1
• 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
• 241000863480 Vinca Species 0.000 description 1
• 240000006365 Vitis vinifera Species 0.000 description 1
• 235000014787 Vitis vinifera Nutrition 0.000 description 1
• 206010048215 Xanthomatosis Diseases 0.000 description 1
• 240000008042 Zea mays Species 0.000 description 1
• 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
• 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
• VVUGXBSXXJTVDS-UHFFFAOYSA-N [4-(dimethylsulfamoyl)phenyl]boronic acid Chemical compound CN(C)S(=O)(=O)C1=CC=C(B(O)O)C=C1 VVUGXBSXXJTVDS-UHFFFAOYSA-N 0.000 description 1
• NDVJJEADFLTFCD-UHFFFAOYSA-N [4-(methanesulfonamido)phenyl]boronic acid Chemical compound CS(=O)(=O)NC1=CC=C(B(O)O)C=C1 NDVJJEADFLTFCD-UHFFFAOYSA-N 0.000 description 1
• UWKSYZHFTGONHY-UHFFFAOYSA-N [4-(methylcarbamoyl)phenyl]boronic acid Chemical compound CNC(=O)C1=CC=C(B(O)O)C=C1 UWKSYZHFTGONHY-UHFFFAOYSA-N 0.000 description 1
• NIDRXNINGRRBFV-UHFFFAOYSA-N [6-(dimethylamino)pyridin-3-yl]boronic acid Chemical compound CN(C)C1=CC=C(B(O)O)C=N1 NIDRXNINGRRBFV-UHFFFAOYSA-N 0.000 description 1
• ZGBSOTLWHZQNLH-UHFFFAOYSA-N [Mg].S(O)(O)(=O)=O Chemical compound [Mg].S(O)(O)(=O)=O ZGBSOTLWHZQNLH-UHFFFAOYSA-N 0.000 description 1
• 150000001241 acetals Chemical class 0.000 description 1
• IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
• 229940048053 acrylate Drugs 0.000 description 1
• 239000012042 active reagent Substances 0.000 description 1
• 230000001154 acute effect Effects 0.000 description 1
• 125000002015 acyclic group Chemical group 0.000 description 1
• 125000004423 acyloxy group Chemical group 0.000 description 1
• YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 1
• 229960000643 adenine Drugs 0.000 description 1
• 210000004100 adrenal gland Anatomy 0.000 description 1
• 239000003463 adsorbent Substances 0.000 description 1
• 230000001476 alcoholic effect Effects 0.000 description 1
• 229940072056 alginate Drugs 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 150000001335 aliphatic alkanes Chemical class 0.000 description 1
• 125000003342 alkenyl group Chemical group 0.000 description 1
• 125000004450 alkenylene group Chemical group 0.000 description 1
• 229940098174 alkeran Drugs 0.000 description 1
• 125000003545 alkoxy group Chemical group 0.000 description 1
• 125000004414 alkyl thio group Chemical group 0.000 description 1
• 125000000304 alkynyl group Chemical group 0.000 description 1
• 125000004419 alkynylene group Chemical group 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• 235000012211 aluminium silicate Nutrition 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• MMQBNYIQPRRIAW-UHFFFAOYSA-N amino 4-methoxybenzoate Chemical compound NOC(=O)C1=CC=C(C=C1)OC.COC1=CC=C(C=C1)C(=O)ON MMQBNYIQPRRIAW-UHFFFAOYSA-N 0.000 description 1
• 235000019257 ammonium acetate Nutrition 0.000 description 1
• 229940043376 ammonium acetate Drugs 0.000 description 1
• 239000000908 ammonium hydroxide Substances 0.000 description 1
• 238000012435 analytical chromatography Methods 0.000 description 1
• 238000002399 angioplasty Methods 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
• 230000003474 anti-emetic effect Effects 0.000 description 1
• 230000003432 anti-folate effect Effects 0.000 description 1
• 230000001946 anti-microtubular Effects 0.000 description 1
• 229940044684 anti-microtubule agent Drugs 0.000 description 1
• 230000000692 anti-sense effect Effects 0.000 description 1
• 230000000259 anti-tumor effect Effects 0.000 description 1
• 239000002111 antiemetic agent Substances 0.000 description 1
• 229940127074 antifolate Drugs 0.000 description 1
• 229940034982 antineoplastic agent Drugs 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 239000000074 antisense oligonucleotide Substances 0.000 description 1
• 238000012230 antisense oligonucleotides Methods 0.000 description 1
• 150000004945 aromatic hydrocarbons Chemical group 0.000 description 1
• 206010003246 arthritis Diseases 0.000 description 1
• 239000008122 artificial sweetener Substances 0.000 description 1
• 235000021311 artificial sweeteners Nutrition 0.000 description 1
• 125000001769 aryl amino group Chemical group 0.000 description 1
• 125000004104 aryloxy group Chemical group 0.000 description 1
• 229940072107 ascorbate Drugs 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 210000001130 astrocyte Anatomy 0.000 description 1
• 238000011914 asymmetric synthesis Methods 0.000 description 1
• 125000004429 atom Chemical group 0.000 description 1
• 238000000889 atomisation Methods 0.000 description 1
• 229960002170 azathioprine Drugs 0.000 description 1
• LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
• 125000000751 azo group Chemical group [*]N=N[*] 0.000 description 1
• 239000000022 bacteriostatic agent Substances 0.000 description 1
• 239000011324 bead Substances 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• 229940077388 benzenesulfonate Drugs 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 229940108502 bicnu Drugs 0.000 description 1
• 210000003445 biliary tract Anatomy 0.000 description 1
• 239000003124 biologic agent Substances 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 239000004305 biphenyl Substances 0.000 description 1
• 235000010290 biphenyl Nutrition 0.000 description 1
• 230000000903 blocking effect Effects 0.000 description 1
• 210000000988 bone and bone Anatomy 0.000 description 1
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
• 210000003123 bronchiole Anatomy 0.000 description 1
• 208000003362 bronchogenic carcinoma Diseases 0.000 description 1
• 201000002143 bronchus adenoma Diseases 0.000 description 1
• OBNCKNCVKJNDBV-UHFFFAOYSA-N butanoic acid ethyl ester Natural products CCCC(=O)OCC OBNCKNCVKJNDBV-UHFFFAOYSA-N 0.000 description 1
• 229910000019 calcium carbonate Inorganic materials 0.000 description 1
• FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
• CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
• 239000008116 calcium stearate Substances 0.000 description 1
• 235000013539 calcium stearate Nutrition 0.000 description 1
• 229940088954 camptosar Drugs 0.000 description 1
• 208000035269 cancer or benign tumor Diseases 0.000 description 1
• 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
• 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
• 125000005708 carbonyloxy group Chemical group [*:2]OC([*:1])=O 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 229940105329 carboxymethylcellulose Drugs 0.000 description 1
• 229960002412 cediranib Drugs 0.000 description 1
• 230000011712 cell development Effects 0.000 description 1
• 230000024245 cell differentiation Effects 0.000 description 1
• 230000010261 cell growth Effects 0.000 description 1
• 230000004709 cell invasion Effects 0.000 description 1
• 201000010881 cervical cancer Diseases 0.000 description 1
• 229960005395 cetuximab Drugs 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• ARQRPTNYUOLOGH-UHFFFAOYSA-N chcl3 chloroform Chemical compound ClC(Cl)Cl.ClC(Cl)Cl ARQRPTNYUOLOGH-UHFFFAOYSA-N 0.000 description 1
• 238000001311 chemical methods and process Methods 0.000 description 1
• 238000005660 chlorination reaction Methods 0.000 description 1
• KVSASDOGYIBWTA-UHFFFAOYSA-N chloro benzoate Chemical compound ClOC(=O)C1=CC=CC=C1 KVSASDOGYIBWTA-UHFFFAOYSA-N 0.000 description 1
• 201000005217 chondroblastoma Diseases 0.000 description 1
• 230000001684 chronic effect Effects 0.000 description 1
• 229940001468 citrate Drugs 0.000 description 1
• 229960002436 cladribine Drugs 0.000 description 1
• 208000009060 clear cell adenocarcinoma Diseases 0.000 description 1
• 238000011260 co-administration Methods 0.000 description 1
• 239000008119 colloidal silica Substances 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000007906 compression Methods 0.000 description 1
• 230000006835 compression Effects 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 1
• 235000005822 corn Nutrition 0.000 description 1
• 229940088547 cosmegen Drugs 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 201000007241 cutaneous T cell lymphoma Diseases 0.000 description 1
• 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
• 239000002875 cyclin dependent kinase inhibitor Substances 0.000 description 1
• 229940043378 cyclin-dependent kinase inhibitor Drugs 0.000 description 1
• CCQPAEQGAVNNIA-UHFFFAOYSA-N cyclobutane-1,1-dicarboxylic acid Chemical compound OC(=O)C1(C(O)=O)CCC1 CCQPAEQGAVNNIA-UHFFFAOYSA-N 0.000 description 1
• AQOZZSWECZTDNR-UHFFFAOYSA-N cyclobutylhydrazine;hydrochloride Chemical compound Cl.NNC1CCC1 AQOZZSWECZTDNR-UHFFFAOYSA-N 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
• GONHTJWVIZVBOU-UHFFFAOYSA-N cyclopentylhydrazine;hydron;chloride Chemical compound Cl.NNC1CCCC1 GONHTJWVIZVBOU-UHFFFAOYSA-N 0.000 description 1
• UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical class O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 1
• 229940104302 cytosine Drugs 0.000 description 1
• 231100000433 cytotoxic Toxicity 0.000 description 1
• 230000003013 cytotoxicity Effects 0.000 description 1
• 231100000135 cytotoxicity Toxicity 0.000 description 1
• GYOZYWVXFNDGLU-XLPZGREQSA-N dTMP Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)C1 GYOZYWVXFNDGLU-XLPZGREQSA-N 0.000 description 1
• 229940107841 daunoxome Drugs 0.000 description 1
• 230000007423 decrease Effects 0.000 description 1
• 238000007872 degassing Methods 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 238000010511 deprotection reaction Methods 0.000 description 1
• 239000002274 desiccant Substances 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
• 235000019700 dicalcium phosphate Nutrition 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 1
• UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
• 229930004069 diterpene Natural products 0.000 description 1
• ODCCJTMPMUFERV-UHFFFAOYSA-N ditert-butyl carbonate Chemical group CC(C)(C)OC(=O)OC(C)(C)C ODCCJTMPMUFERV-UHFFFAOYSA-N 0.000 description 1
• 230000035619 diuresis Effects 0.000 description 1
• UZZWBUYVTBPQIV-UHFFFAOYSA-N dme dimethoxyethane Chemical compound COCCOC.COCCOC UZZWBUYVTBPQIV-UHFFFAOYSA-N 0.000 description 1
• 239000003968 dna methyltransferase inhibitor Substances 0.000 description 1
• POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
• 230000005782 double-strand break Effects 0.000 description 1
• 239000000890 drug combination Substances 0.000 description 1
• 239000012039 electrophile Substances 0.000 description 1
• 238000000132 electrospray ionisation Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 210000004696 endometrium Anatomy 0.000 description 1
• 239000007920 enema Substances 0.000 description 1
• 229940079360 enema for constipation Drugs 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 239000003623 enhancer Substances 0.000 description 1
• 230000008995 epigenetic change Effects 0.000 description 1
• 230000004049 epigenetic modification Effects 0.000 description 1
• 210000002919 epithelial cell Anatomy 0.000 description 1
• 208000010932 epithelial neoplasm Diseases 0.000 description 1
• 229960001433 erlotinib Drugs 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 1
• 150000002170 ethers Chemical class 0.000 description 1
• 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 description 1
• KTMGNAIGXYODKQ-SREVYHEPSA-N ethyl (z)-2-cyano-3-ethoxyprop-2-enoate Chemical compound CCO\C=C(\C#N)C(=O)OCC KTMGNAIGXYODKQ-SREVYHEPSA-N 0.000 description 1
• WHXZBFMHKIICHR-UHFFFAOYSA-N ethyl 1-tert-butyl-3-methyl-6-oxo-7H-pyrazolo[3,4-b]pyridine-4-carboxylate Chemical compound CCOC(=O)C1=CC(=O)NC2=C1C(C)=NN2C(C)(C)C WHXZBFMHKIICHR-UHFFFAOYSA-N 0.000 description 1
• OFSRMXPYRMMISS-UHFFFAOYSA-N ethyl 5-amino-1-propan-2-ylpyrazole-4-carboxylate Chemical compound CCOC(=O)C=1C=NN(C(C)C)C=1N OFSRMXPYRMMISS-UHFFFAOYSA-N 0.000 description 1
• XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
• 210000003527 eukaryotic cell Anatomy 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 230000001605 fetal effect Effects 0.000 description 1
• 239000012065 filter cake Substances 0.000 description 1
• 239000005454 flavour additive Substances 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
• 229960005304 fludarabine phosphate Drugs 0.000 description 1
• 239000012530 fluid Substances 0.000 description 1
• 150000005699 fluoropyrimidines Chemical class 0.000 description 1
• 239000004052 folic acid antagonist Substances 0.000 description 1
• 201000003444 follicular lymphoma Diseases 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
• 229940050411 fumarate Drugs 0.000 description 1
• 201000010175 gallbladder cancer Diseases 0.000 description 1
• 208000015419 gastrin-producing neuroendocrine tumor Diseases 0.000 description 1
• 201000000052 gastrinoma Diseases 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• OKKDEIYWILRZIA-OSZBKLCCSA-N gemcitabine hydrochloride Chemical compound [H+].[Cl-].O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 OKKDEIYWILRZIA-OSZBKLCCSA-N 0.000 description 1
• 229940020967 gemzar Drugs 0.000 description 1
• 230000014509 gene expression Effects 0.000 description 1
• 230000030279 gene silencing Effects 0.000 description 1
• 201000003115 germ cell cancer Diseases 0.000 description 1
• 229940080856 gleevec Drugs 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 235000001727 glucose Nutrition 0.000 description 1
• 229930195712 glutamate Natural products 0.000 description 1
• 229940049906 glutamate Drugs 0.000 description 1
• JFCQEDHGNNZCLN-UHFFFAOYSA-N glutaric acid Chemical compound OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
• 229930182470 glycoside Natural products 0.000 description 1
• 150000002338 glycosides Chemical class 0.000 description 1
• PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
• 229910052737 gold Inorganic materials 0.000 description 1
• 239000010931 gold Substances 0.000 description 1
• 238000005469 granulation Methods 0.000 description 1
• 230000003179 granulation Effects 0.000 description 1
• 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
• 208000006359 hepatoblastoma Diseases 0.000 description 1
• 201000002735 hepatocellular adenoma Diseases 0.000 description 1
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
• 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
• 210000003494 hepatocyte Anatomy 0.000 description 1
• MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
• 229940022353 herceptin Drugs 0.000 description 1
• 125000000623 heterocyclic group Chemical group 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
• 229940121372 histone deacetylase inhibitor Drugs 0.000 description 1
• 230000006197 histone deacetylation Effects 0.000 description 1
• 229940088013 hycamtin Drugs 0.000 description 1
• 230000036571 hydration Effects 0.000 description 1
• 238000006703 hydration reaction Methods 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• 239000004093 hydrolase inhibitor Substances 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• 206010020718 hyperplasia Diseases 0.000 description 1
• 229960003685 imatinib mesylate Drugs 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 239000002955 immunomodulating agent Substances 0.000 description 1
• 201000004933 in situ carcinoma Diseases 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 238000001727 in vivo Methods 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 239000003999 initiator Substances 0.000 description 1
• CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
• 229960000367 inositol Drugs 0.000 description 1
• 206010022498 insulinoma Diseases 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 238000007918 intramuscular 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
• 150000002500 ions Chemical class 0.000 description 1
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical class OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 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
• KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• TWBYWOBDOCUKOW-UHFFFAOYSA-M isonicotinate Chemical compound [O-]C(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-M 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
• 210000001117 keloid Anatomy 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 208000022013 kidney Wilms tumor Diseases 0.000 description 1
• 229940043355 kinase inhibitor Drugs 0.000 description 1
• 229960004891 lapatinib Drugs 0.000 description 1
• 210000002429 large intestine Anatomy 0.000 description 1
• 210000000867 larynx Anatomy 0.000 description 1
• 229940070765 laurate Drugs 0.000 description 1
• 231100001022 leukopenia Toxicity 0.000 description 1
• 206010024627 liposarcoma Diseases 0.000 description 1
• 239000002502 liposome Substances 0.000 description 1
• 238000004811 liquid chromatography Methods 0.000 description 1
• 230000009063 long-term regulation Effects 0.000 description 1
• 230000000527 lymphocytic effect Effects 0.000 description 1
• 208000025036 lymphosarcoma Diseases 0.000 description 1
• JMZFEHDNIAQMNB-UHFFFAOYSA-N m-aminophenylboronic acid Chemical compound NC1=CC=CC(B(O)O)=C1 JMZFEHDNIAQMNB-UHFFFAOYSA-N 0.000 description 1
• 201000004792 malaria Diseases 0.000 description 1
• 229940049920 malate Drugs 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
• BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 201000004593 malignant giant cell tumor Diseases 0.000 description 1
• 201000000289 malignant teratoma Diseases 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
• BCVXHSPFUWZLGQ-UHFFFAOYSA-N mecn acetonitrile Chemical compound CC#N.CC#N BCVXHSPFUWZLGQ-UHFFFAOYSA-N 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 210000002418 meninge Anatomy 0.000 description 1
• 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
• COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
• WFFQYWAAEWLHJC-UHFFFAOYSA-N mercaptopurine hydrate Chemical compound O.S=C1NC=NC2=C1NC=N2 WFFQYWAAEWLHJC-UHFFFAOYSA-N 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• 230000031864 metaphase Effects 0.000 description 1
• 208000037819 metastatic cancer Diseases 0.000 description 1
• 208000011575 metastatic malignant neoplasm Diseases 0.000 description 1
• 208000021039 metastatic melanoma Diseases 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 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
• DASQOOZCTWOQPA-GXKRWWSZSA-L methotrexate disodium Chemical compound [Na+].[Na+].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 DASQOOZCTWOQPA-GXKRWWSZSA-L 0.000 description 1
• UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
• IZYBEMGNIUSSAX-UHFFFAOYSA-N methyl benzenecarboperoxoate Chemical compound COOC(=O)C1=CC=CC=C1 IZYBEMGNIUSSAX-UHFFFAOYSA-N 0.000 description 1
• 229940095102 methyl benzoate Drugs 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• LRMHVVPPGGOAJQ-UHFFFAOYSA-N methyl nitrate Chemical compound CO[N+]([O-])=O LRMHVVPPGGOAJQ-UHFFFAOYSA-N 0.000 description 1
• 230000011987 methylation Effects 0.000 description 1
• 238000007069 methylation reaction Methods 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 231100000782 microtubule inhibitor Toxicity 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 125000002950 monocyclic group Chemical group 0.000 description 1
• 150000004682 monohydrates Chemical class 0.000 description 1
• 210000000214 mouth Anatomy 0.000 description 1
• 208000010492 mucinous cystadenocarcinoma Diseases 0.000 description 1
• 210000003097 mucus Anatomy 0.000 description 1
• 201000005962 mycosis fungoides Diseases 0.000 description 1
• 208000009091 myxoma Diseases 0.000 description 1
• DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 1
• TYHXIJJQIJKFSO-UHFFFAOYSA-N n'-pyridin-2-ylethane-1,2-diamine Chemical compound NCCNC1=CC=CC=N1 TYHXIJJQIJKFSO-UHFFFAOYSA-N 0.000 description 1
• DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 description 1
• CPVQOGUURKEJJM-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-yl-6-(1h-pyrazol-4-yl)pyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C=1C=NNC=1 CPVQOGUURKEJJM-UHFFFAOYSA-N 0.000 description 1
• LYTGPDCLJDARQE-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-yl-6-(pyridin-4-ylmethylamino)pyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1NCC1=CC=NC=C1 LYTGPDCLJDARQE-UHFFFAOYSA-N 0.000 description 1
• MPJYQHLASWTWKG-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-1-propan-2-yl-6-[2-(pyridin-2-ylamino)ethylamino]pyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1NCCNC1=CC=CC=N1 MPJYQHLASWTWKG-UHFFFAOYSA-N 0.000 description 1
• UVODPARGBXNUQU-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-3-methyl-6-[4-(methylsulfamoyl)phenyl]-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound C1=CC(S(=O)(=O)NC)=CC=C1C1=CC(C(=O)NCC=2C(NC(C)=CC=2C)=O)=C(C(C)=NN2C(C)C)C2=N1 UVODPARGBXNUQU-UHFFFAOYSA-N 0.000 description 1
• SWERKTWCPWPYOB-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-6-(2,4-dioxo-1h-pyrimidin-5-yl)-1-propan-2-ylpyrazolo[3,4-b]pyridine-4-carboxamide Chemical compound N1=C2N(C(C)C)N=CC2=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C=C1C1=CNC(=O)NC1=O SWERKTWCPWPYOB-UHFFFAOYSA-N 0.000 description 1
• VRVLTKRJAJYXLT-UHFFFAOYSA-N n-[2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl]cyclopropanesulfonamide Chemical compound COC1=NC=C(B2OC(C)(C)C(C)(C)O2)C=C1NS(=O)(=O)C1CC1 VRVLTKRJAJYXLT-UHFFFAOYSA-N 0.000 description 1
• YCWPTBAHVWJMEY-UHFFFAOYSA-N n-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]acetamide Chemical compound C1=NC(NC(=O)C)=CC=C1B1OC(C)(C)C(C)(C)O1 YCWPTBAHVWJMEY-UHFFFAOYSA-N 0.000 description 1
• UXJVHVXONVGHIL-UHFFFAOYSA-N n-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl]benzenesulfonamide Chemical compound O1C(C)(C)C(C)(C)OB1C1=CN=CC(NS(=O)(=O)C=2C=CC=CC=2)=C1 UXJVHVXONVGHIL-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• LUMBLRWRRONQMO-UHFFFAOYSA-N n-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC=C1B1OC(C)(C)C(C)(C)O1 LUMBLRWRRONQMO-UHFFFAOYSA-N 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 1
• KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 229930014626 natural product Natural products 0.000 description 1
• 235000021096 natural sweeteners Nutrition 0.000 description 1
• 229940086322 navelbine Drugs 0.000 description 1
• 231100000417 nephrotoxicity Toxicity 0.000 description 1
• 230000007694 nephrotoxicity Effects 0.000 description 1
• 208000023833 nerve sheath neoplasm Diseases 0.000 description 1
• 210000000653 nervous system Anatomy 0.000 description 1
• 210000004498 neuroglial cell Anatomy 0.000 description 1
• 230000000926 neurological effect Effects 0.000 description 1
• 208000004649 neutrophil actin dysfunction Diseases 0.000 description 1
• 238000006396 nitration reaction Methods 0.000 description 1
• VWBWQOUWDOULQN-UHFFFAOYSA-N nmp n-methylpyrrolidone Chemical compound CN1CCCC1=O.CN1CCCC1=O VWBWQOUWDOULQN-UHFFFAOYSA-N 0.000 description 1
• 108091027963 non-coding RNA Proteins 0.000 description 1
• 102000042567 non-coding RNA Human genes 0.000 description 1
• 102000037979 non-receptor tyrosine kinases Human genes 0.000 description 1
• 108091008046 non-receptor tyrosine kinases Proteins 0.000 description 1
• 108020004707 nucleic acids Proteins 0.000 description 1
• 102000039446 nucleic acids Human genes 0.000 description 1
• 230000000269 nucleophilic effect Effects 0.000 description 1
• 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
• QWVGKYWNOKOFNN-UHFFFAOYSA-N o-methyl phenol Natural products CC1=CC=CC=C1O QWVGKYWNOKOFNN-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• ZWQAMTPIXASAMC-UHFFFAOYSA-N octane-3,4,5-trione Chemical compound CCCC(=O)C(=O)C(=O)CC ZWQAMTPIXASAMC-UHFFFAOYSA-N 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
• 230000003287 optical effect Effects 0.000 description 1
• 239000010502 orange oil Substances 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000002894 organic compounds Chemical class 0.000 description 1
• 201000008482 osteoarthritis Diseases 0.000 description 1
• 208000008798 osteoma Diseases 0.000 description 1
• 231100000262 ototoxicity Toxicity 0.000 description 1
• 230000002018 overexpression Effects 0.000 description 1
• 210000003101 oviduct Anatomy 0.000 description 1
• AHVQYHFYQWKUKB-UHFFFAOYSA-N oxan-4-amine Chemical compound NC1CCOCC1 AHVQYHFYQWKUKB-UHFFFAOYSA-N 0.000 description 1
• JMJRYTGVHCAYCT-UHFFFAOYSA-N oxan-4-one Chemical compound O=C1CCOCC1 JMJRYTGVHCAYCT-UHFFFAOYSA-N 0.000 description 1
• ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 1
• 208000021255 pancreatic insulinoma Diseases 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
• 239000012188 paraffin wax Substances 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 239000011236 particulate material Substances 0.000 description 1
• 239000006072 paste Substances 0.000 description 1
• 229960000639 pazopanib Drugs 0.000 description 1
• CUIHSIWYWATEQL-UHFFFAOYSA-N pazopanib Chemical compound C1=CC2=C(C)N(C)N=C2C=C1N(C)C(N=1)=CC=NC=1NC1=CC=C(C)C(S(N)(=O)=O)=C1 CUIHSIWYWATEQL-UHFFFAOYSA-N 0.000 description 1
• 229960002340 pentostatin Drugs 0.000 description 1
• FPVKHBSQESCIEP-JQCXWYLXSA-N pentostatin Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC[C@H]2O)=C2N=C1 FPVKHBSQESCIEP-JQCXWYLXSA-N 0.000 description 1
• 235000019477 peppermint oil Nutrition 0.000 description 1
• 239000008177 pharmaceutical agent Substances 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
• 229940049953 phenylacetate Drugs 0.000 description 1
• WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
• RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
• XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• BCIIMDOZSUCSEN-UHFFFAOYSA-N piperidin-4-amine Chemical compound NC1CCNCC1 BCIIMDOZSUCSEN-UHFFFAOYSA-N 0.000 description 1
• 229940063179 platinol Drugs 0.000 description 1
• 150000003057 platinum Chemical class 0.000 description 1
• 231100000374 pneumotoxicity Toxicity 0.000 description 1
• 208000030761 polycystic kidney disease Diseases 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 239000002861 polymer material Substances 0.000 description 1
• 239000003910 polypeptide antibiotic agent Substances 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 229910000027 potassium carbonate Inorganic materials 0.000 description 1
• 229910000160 potassium phosphate Inorganic materials 0.000 description 1
• 235000011009 potassium phosphates Nutrition 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 238000004237 preparative chromatography Methods 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 238000003825 pressing Methods 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
• 230000000861 pro-apoptotic effect Effects 0.000 description 1
• 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
• 125000006410 propenylene group Chemical group 0.000 description 1
• 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
• 238000011471 prostatectomy Methods 0.000 description 1
• 239000011253 protective coating Substances 0.000 description 1
• 230000017854 proteolysis Effects 0.000 description 1
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
• 230000002685 pulmonary effect Effects 0.000 description 1
• IGFXRKMLLMBKSA-UHFFFAOYSA-N purine Chemical compound N1=C[N]C2=NC=NC2=C1 IGFXRKMLLMBKSA-UHFFFAOYSA-N 0.000 description 1
• 239000002213 purine nucleotide Substances 0.000 description 1
• 229940117820 purinethol Drugs 0.000 description 1
• ABMYEXAYWZJVOV-UHFFFAOYSA-N pyridin-3-ylboronic acid Chemical compound OB(O)C1=CC=CN=C1 ABMYEXAYWZJVOV-UHFFFAOYSA-N 0.000 description 1
• 150000003230 pyrimidines Chemical class 0.000 description 1
• 108700042226 ras Genes Proteins 0.000 description 1
• 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
• 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
• 210000000664 rectum Anatomy 0.000 description 1
• 238000007634 remodeling Methods 0.000 description 1
• 230000008439 repair process Effects 0.000 description 1
• 230000003362 replicative effect Effects 0.000 description 1
• 238000012958 reprocessing Methods 0.000 description 1
• 239000013557 residual solvent Substances 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• 201000006845 reticulosarcoma Diseases 0.000 description 1
• 208000029922 reticulum cell sarcoma Diseases 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 238000002390 rotary evaporation Methods 0.000 description 1
• 235000019204 saccharin Nutrition 0.000 description 1
• CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
• 229940081974 saccharin Drugs 0.000 description 1
• 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
• 229960001860 salicylate Drugs 0.000 description 1
• CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• 208000004548 serous cystadenocarcinoma Diseases 0.000 description 1
• 239000004208 shellac Substances 0.000 description 1
• ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
• 229940113147 shellac Drugs 0.000 description 1
• 235000013874 shellac Nutrition 0.000 description 1
• 239000000377 silicon dioxide Substances 0.000 description 1
• 229920002545 silicone oil Polymers 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
• 238000011125 single therapy Methods 0.000 description 1
• 230000005783 single-strand break Effects 0.000 description 1
• 231100000438 skin toxicity Toxicity 0.000 description 1
• 210000003625 skull Anatomy 0.000 description 1
• 239000004055 small Interfering RNA Substances 0.000 description 1
• 208000000587 small cell lung carcinoma Diseases 0.000 description 1
• 210000000813 small intestine Anatomy 0.000 description 1
• 235000010413 sodium alginate Nutrition 0.000 description 1
• 239000000661 sodium alginate Substances 0.000 description 1
• 229940005550 sodium alginate Drugs 0.000 description 1
• WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
• 239000004299 sodium benzoate Substances 0.000 description 1
• 235000010234 sodium benzoate Nutrition 0.000 description 1
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
• RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
• SYXYWTXQFUUWLP-UHFFFAOYSA-N sodium;butan-1-olate Chemical compound [Na+].CCCC[O-] SYXYWTXQFUUWLP-UHFFFAOYSA-N 0.000 description 1
• WGRULTCAYDOGQK-UHFFFAOYSA-M sodium;sodium;hydroxide Chemical compound [OH-].[Na].[Na+] WGRULTCAYDOGQK-UHFFFAOYSA-M 0.000 description 1
• 239000007790 solid phase Substances 0.000 description 1
• 230000003381 solubilizing effect Effects 0.000 description 1
• 229960003787 sorafenib Drugs 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 239000012258 stirred mixture Substances 0.000 description 1
• 210000002536 stromal cell Anatomy 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
• 150000003462 sulfoxides Chemical class 0.000 description 1
• 150000003467 sulfuric acid derivatives Chemical class 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
• 229960001796 sunitinib Drugs 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 230000001629 suppression Effects 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 239000003826 tablet Substances 0.000 description 1
• 229940095374 tabloid Drugs 0.000 description 1
• 229940120982 tarceva Drugs 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 description 1
• 150000004579 taxol derivatives Chemical class 0.000 description 1
• 229940063683 taxotere Drugs 0.000 description 1
• 208000001608 teratocarcinoma Diseases 0.000 description 1
• 150000003505 terpenes Chemical class 0.000 description 1
• 235000007586 terpenes Nutrition 0.000 description 1
• FQAORYQTZLGOBK-UHFFFAOYSA-N tert-butyl 3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indazole-1-carboxylate Chemical compound C1=C2C(C)=NN(C(=O)OC(C)(C)C)C2=CC=C1B1OC(C)(C)C(C)(C)O1 FQAORYQTZLGOBK-UHFFFAOYSA-N 0.000 description 1
• TZRQZPMQUXEZMC-UHFFFAOYSA-N tert-butyl n-(2-bromoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCBr TZRQZPMQUXEZMC-UHFFFAOYSA-N 0.000 description 1
• DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 1
• CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
• 150000003512 tertiary amines Chemical class 0.000 description 1
• 210000001550 testis Anatomy 0.000 description 1
• WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
• PHCBRBWANGJMHS-UHFFFAOYSA-J tetrasodium;disulfate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O PHCBRBWANGJMHS-UHFFFAOYSA-J 0.000 description 1
• WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 125000002480 thymidyl group Chemical group 0.000 description 1
• 210000001685 thyroid gland Anatomy 0.000 description 1
• 210000001519 tissue Anatomy 0.000 description 1
• 238000004448 titration Methods 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 230000002110 toxicologic effect Effects 0.000 description 1
• 231100000759 toxicological effect Toxicity 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• BWHOZHOGCMHOBV-BQYQJAHWSA-N trans-benzylideneacetone Chemical compound CC(=O)\C=C\C1=CC=CC=C1 BWHOZHOGCMHOBV-BQYQJAHWSA-N 0.000 description 1
• JHHZQADGLDKIPM-UHFFFAOYSA-N trans-hept-3-en-2-one Natural products CCCC=CC(C)=O JHHZQADGLDKIPM-UHFFFAOYSA-N 0.000 description 1
• 206010044412 transitional cell carcinoma Diseases 0.000 description 1
• 229960000575 trastuzumab Drugs 0.000 description 1
• 238000011269 treatment regimen Methods 0.000 description 1
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
• 150000004684 trihydrates Chemical class 0.000 description 1
• 239000001226 triphosphate Substances 0.000 description 1
• 235000011178 triphosphate Nutrition 0.000 description 1
• 125000002264 triphosphate group Chemical class [H]OP(=O)(O[H])OP(=O)(O[H])OP(=O)(O[H])O* 0.000 description 1
• 201000007423 tubular adenocarcinoma Diseases 0.000 description 1
• 208000022271 tubular adenoma Diseases 0.000 description 1
• 230000004614 tumor growth Effects 0.000 description 1
• 229940094060 tykerb Drugs 0.000 description 1
• 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
• 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
• 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
• JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
• 210000003708 urethra Anatomy 0.000 description 1
• 210000004291 uterus Anatomy 0.000 description 1
• 229960005486 vaccine Drugs 0.000 description 1
• 210000001215 vagina Anatomy 0.000 description 1
• 239000006216 vaginal suppository Substances 0.000 description 1
• 229940070710 valerate Drugs 0.000 description 1
• NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
• MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 description 1
• 229960000241 vandetanib Drugs 0.000 description 1
• UHTHHESEBZOYNR-UHFFFAOYSA-N vandetanib Chemical compound COC1=CC(C(/N=CN2)=N/C=3C(=CC(Br)=CC=3)F)=C2C=C1OCC1CCN(C)CC1 UHTHHESEBZOYNR-UHFFFAOYSA-N 0.000 description 1
• 229950000578 vatalanib Drugs 0.000 description 1
• YCOYDOIWSSHVCK-UHFFFAOYSA-N vatalanib Chemical compound C1=CC(Cl)=CC=C1NC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 YCOYDOIWSSHVCK-UHFFFAOYSA-N 0.000 description 1
• 208000009540 villous adenoma Diseases 0.000 description 1
• CILBMBUYJCWATM-PYGJLNRPSA-N vinorelbine ditartrate Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.OC(=O)[C@H](O)[C@@H](O)C(O)=O.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 CILBMBUYJCWATM-PYGJLNRPSA-N 0.000 description 1
• 229960002166 vinorelbine tartrate Drugs 0.000 description 1
• GBABOYUKABKIAF-IWWDSPBFSA-N vinorelbinetartrate Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC(C23[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-IWWDSPBFSA-N 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• WAEXFXRVDQXREF-UHFFFAOYSA-N vorinostat Chemical compound ONC(=O)CCCCCCC(=O)NC1=CC=CC=C1 WAEXFXRVDQXREF-UHFFFAOYSA-N 0.000 description 1
• 229960000237 vorinostat Drugs 0.000 description 1
• 210000003905 vulva Anatomy 0.000 description 1
• 239000008215 water for injection Substances 0.000 description 1
• 230000029663 wound healing Effects 0.000 description 1
• 238000002424 x-ray crystallography Methods 0.000 description 1
• 239000000230 xanthan gum Substances 0.000 description 1
• 235000010493 xanthan gum Nutrition 0.000 description 1
• 229920001285 xanthan gum Polymers 0.000 description 1
• 229940082509 xanthan gum Drugs 0.000 description 1
• 150000003751 zinc Chemical class 0.000 description 1
• 229930195724 β-lactose Natural products 0.000 description 1