TWI503322B - 作為ｃｄｋ４／６抑制劑之吡咯并嘧啶化合物 - Google Patents

Info

Publication number

TWI503322B

TWI503322B TW100105536A TW100105536A TWI503322B TW I503322 B TWI503322 B TW I503322B TW 100105536 A TW100105536 A TW 100105536A TW 100105536 A TW100105536 A TW 100105536A TW I503322 B TWI503322 B TW I503322B

Authority

TW

Taiwan

Prior art keywords

pyrrolo

ylamino

cyclopentyl

pyridin

diazabicyclo

Prior art date

2010-02-19

Links

• Espacenet
• Global Dossier
• Discuss

• 239000003112 inhibitor Substances 0.000 title description 25
• 150000004944 pyrrolopyrimidines Chemical class 0.000 title description 3
• 101100005789 Caenorhabditis elegans cdk-4 gene Proteins 0.000 title 1
• -1 bicyclo [2.2.1] heptyl Chemical group 0.000 claims description 259
• 150000001875 compounds Chemical class 0.000 claims description 188
• 239000002253 acid Substances 0.000 claims description 180
• YWWNNLPSZSEZNZ-UHFFFAOYSA-N n,n-dimethyldecan-1-amine Chemical compound CCCCCCCCCCN(C)C YWWNNLPSZSEZNZ-UHFFFAOYSA-N 0.000 claims description 154
• 229910052739 hydrogen Inorganic materials 0.000 claims description 114
• 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 claims description 91
• 150000003839 salts Chemical class 0.000 claims description 86
• 125000000217 alkyl group Chemical group 0.000 claims description 37
• 125000001424 substituent group Chemical group 0.000 claims description 26
• 239000008194 pharmaceutical composition Substances 0.000 claims description 25
• 239000001257 hydrogen Substances 0.000 claims description 22
• JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 21
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 19
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 16
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 14
• 229910052799 carbon Inorganic materials 0.000 claims description 12
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
• ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 claims description 11
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
• 229910052760 oxygen Inorganic materials 0.000 claims description 11
• 239000000126 substance Substances 0.000 claims description 11
• WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 claims description 10
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 9
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 9
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 9
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
• 239000001301 oxygen Substances 0.000 claims description 7
• 238000006467 substitution reaction Methods 0.000 claims description 7
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 6
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
• 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 claims description 6
• 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 6
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([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
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
• 150000002431 hydrogen Chemical class 0.000 claims description 5
• 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims description 4
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 4
• 229910052805 deuterium Inorganic materials 0.000 claims description 4
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
• BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Substances OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 3
• 229910052736 halogen Inorganic materials 0.000 claims description 3
• 150000002367 halogens Chemical class 0.000 claims description 3
• PXFIUPLVBBAUKD-WMZOPIPTSA-N 2-[[5-[(3as,7ar)-6-oxo-2,3,3a,4,7,7a-hexahydro-1h-pyrrolo[3,4-c]pyridin-5-yl]pyridin-2-yl]amino]-7-cyclopentyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(C[C@H]4CNC[C@H]4C3)=O)N=C2N1C1CCCC1 PXFIUPLVBBAUKD-WMZOPIPTSA-N 0.000 claims description 2
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
• 125000003386 piperidinyl group Chemical group 0.000 claims description 2
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
• ILJXIWRDZSPWPF-UHFFFAOYSA-N 3,4-dimethyl-1H-indol-2-amine Chemical compound CC1=C2C(=C(NC2=CC=C1)N)C ILJXIWRDZSPWPF-UHFFFAOYSA-N 0.000 claims 1
• 125000001475 halogen functional group Chemical group 0.000 claims 1
• 238000002360 preparation method Methods 0.000 description 270
• 238000000034 method Methods 0.000 description 263
• 238000005481 NMR spectroscopy Methods 0.000 description 248
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 190
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 122
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 117
• 239000000203 mixture Substances 0.000 description 117
• 238000006243 chemical reaction Methods 0.000 description 92
• 235000019439 ethyl acetate Nutrition 0.000 description 80
• 230000008878 coupling Effects 0.000 description 74
• 238000010168 coupling process Methods 0.000 description 74
• 238000005859 coupling reaction Methods 0.000 description 74
• 125000006239 protecting group Chemical group 0.000 description 69
• 239000007787 solid Substances 0.000 description 66
• 230000015572 biosynthetic process Effects 0.000 description 63
• 239000000243 solution Substances 0.000 description 63
• 206010028980 Neoplasm Diseases 0.000 description 58
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 52
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 50
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 46
• 210000004027 cell Anatomy 0.000 description 44
• 239000011541 reaction mixture Substances 0.000 description 44
• 101000715943 Caenorhabditis elegans Cyclin-dependent kinase 4 homolog Proteins 0.000 description 43
• 239000011734 sodium Substances 0.000 description 43
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 42
• 238000004896 high resolution mass spectrometry Methods 0.000 description 41
• 239000000460 chlorine Substances 0.000 description 40
• 201000010099 disease Diseases 0.000 description 38
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 38
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 37
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical class OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 34
• 239000003814 drug Substances 0.000 description 34
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 30
• 201000011510 cancer Diseases 0.000 description 30
• 239000011664 nicotinic acid Substances 0.000 description 28
• 230000000694 effects Effects 0.000 description 27
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 26
• 239000012267 brine Substances 0.000 description 26
• 229960003512 nicotinic acid Drugs 0.000 description 26
• 229910052757 nitrogen Inorganic materials 0.000 description 26
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 26
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
• 239000000543 intermediate Substances 0.000 description 25
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 25
• 238000000746 purification Methods 0.000 description 25
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 23
• MHZGKXUYDGKKIU-UHFFFAOYSA-N Decylamine Chemical compound CCCCCCCCCCN MHZGKXUYDGKKIU-UHFFFAOYSA-N 0.000 description 23
• 239000012044 organic layer Substances 0.000 description 23
• 239000000725 suspension Substances 0.000 description 23
• VZXTWGWHSMCWGA-UHFFFAOYSA-N 1,3,5-triazine-2,4-diamine Chemical compound NC1=NC=NC(N)=N1 VZXTWGWHSMCWGA-UHFFFAOYSA-N 0.000 description 22
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 22
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 22
• 239000002904 solvent Substances 0.000 description 22
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
• 238000006722 reduction reaction Methods 0.000 description 21
• 230000009467 reduction Effects 0.000 description 20
• 230000001404 mediated effect Effects 0.000 description 19
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 18
• 125000000449 nitro group Chemical class [O-][N+](*)=O 0.000 description 18
• 229940124597 therapeutic agent Drugs 0.000 description 18
• ATXXLNCPVSUCNK-UHFFFAOYSA-N 5-bromo-2-nitropyridine Chemical compound [O-][N+](=O)C1=CC=C(Br)C=N1 ATXXLNCPVSUCNK-UHFFFAOYSA-N 0.000 description 17
• 102100036252 Cyclin-dependent kinase 4 Human genes 0.000 description 17
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
• 239000003795 chemical substances by application Substances 0.000 description 17
• 108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 description 16
• 150000001412 amines Chemical class 0.000 description 16
• 150000002148 esters Chemical class 0.000 description 16
• 235000001968 nicotinic acid Nutrition 0.000 description 16
• 229940002612 prodrug Drugs 0.000 description 16
• 239000000651 prodrug Substances 0.000 description 16
• DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 16
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 15
• 102100038042 Retinoblastoma-associated protein Human genes 0.000 description 15
• 238000003556 assay Methods 0.000 description 15
• 239000000706 filtrate Substances 0.000 description 15
• 229960002715 nicotine Drugs 0.000 description 15
• 238000003199 nucleic acid amplification method Methods 0.000 description 15
• 239000012071 phase Substances 0.000 description 15
• DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 14
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 14
• 230000003321 amplification Effects 0.000 description 14
• 238000004587 chromatography analysis Methods 0.000 description 14
• OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 14
• 238000004809 thin layer chromatography Methods 0.000 description 14
• 102000016736 Cyclin Human genes 0.000 description 13
• 108050006400 Cyclin Proteins 0.000 description 13
• 239000012043 crude product Substances 0.000 description 13
• 238000007429 general method Methods 0.000 description 13
• 230000005764 inhibitory process Effects 0.000 description 13
• IHWDSEPNZDYMNF-UHFFFAOYSA-N 1H-indol-2-amine Chemical compound C1=CC=C2NC(N)=CC2=C1 IHWDSEPNZDYMNF-UHFFFAOYSA-N 0.000 description 12
• 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 12
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
• 208000025205 Mantle-Cell Lymphoma Diseases 0.000 description 12
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 12
• YNBADRVTZLEFNH-UHFFFAOYSA-N methyl nicotinate Chemical compound COC(=O)C1=CC=CN=C1 YNBADRVTZLEFNH-UHFFFAOYSA-N 0.000 description 12
• 238000003756 stirring Methods 0.000 description 12
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 12
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 11
• 239000007864 aqueous solution Substances 0.000 description 11
• 238000004440 column chromatography Methods 0.000 description 11
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 11
• 229940079593 drug Drugs 0.000 description 11
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 11
• 206010006187 Breast cancer Diseases 0.000 description 10
• 208000026310 Breast neoplasm Diseases 0.000 description 10
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
• 239000004480 active ingredient Substances 0.000 description 10
• 125000004429 atom Chemical group 0.000 description 10
• 239000002585 base Substances 0.000 description 10
• 239000002552 dosage form Substances 0.000 description 10
• 238000011534 incubation Methods 0.000 description 10
• 239000002609 medium Substances 0.000 description 10
• 208000002154 non-small cell lung carcinoma Diseases 0.000 description 10
• 108090000623 proteins and genes Proteins 0.000 description 10
• HKSQZEGSMBFHGC-UHFFFAOYSA-N pyrimidine-4-carboxamide Chemical compound NC(=O)C1=CC=NC=N1 HKSQZEGSMBFHGC-UHFFFAOYSA-N 0.000 description 10
• 238000000926 separation method Methods 0.000 description 10
• RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 10
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 10
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 9
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• 239000010410 layer Substances 0.000 description 9
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 9
• 201000001441 melanoma Diseases 0.000 description 9
• 201000002528 pancreatic cancer Diseases 0.000 description 9
• 208000008443 pancreatic carcinoma Diseases 0.000 description 9
• 238000005932 reductive alkylation reaction Methods 0.000 description 9
• 229920006395 saturated elastomer Polymers 0.000 description 9
• 238000010898 silica gel chromatography Methods 0.000 description 9
• 238000003786 synthesis reaction Methods 0.000 description 9
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
• PMDDQOHZLBZUSO-UHFFFAOYSA-N 2-chloro-7-cyclopentyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(Cl)N=C2N1C1CCCC1 PMDDQOHZLBZUSO-UHFFFAOYSA-N 0.000 description 8
• 102000006311 Cyclin D1 Human genes 0.000 description 8
• 206010057190 Respiratory tract infections Diseases 0.000 description 8
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 8
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 8
• 239000000463 material Substances 0.000 description 8
• 230000026731 phosphorylation Effects 0.000 description 8
• 238000006366 phosphorylation reaction Methods 0.000 description 8
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
• 239000000047 product Substances 0.000 description 8
• 102000004169 proteins and genes Human genes 0.000 description 8
• 238000012552 review Methods 0.000 description 8
• 229910052708 sodium Inorganic materials 0.000 description 8
• 229910052938 sodium sulfate Inorganic materials 0.000 description 8
• 235000011152 sodium sulphate Nutrition 0.000 description 8
• HNINFCBLGHCFOJ-UHFFFAOYSA-N tert-butyl 3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound C1NCC2CCC1N2C(=O)OC(C)(C)C HNINFCBLGHCFOJ-UHFFFAOYSA-N 0.000 description 8
• 108010058546 Cyclin D1 Proteins 0.000 description 7
• 108010025468 Cyclin-Dependent Kinase 6 Proteins 0.000 description 7
• 102100026804 Cyclin-dependent kinase 6 Human genes 0.000 description 7
• 210000004128 D cell Anatomy 0.000 description 7
• 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 7
• 239000000872 buffer Substances 0.000 description 7
• 229910002091 carbon monoxide Inorganic materials 0.000 description 7
• 238000010348 incorporation Methods 0.000 description 7
• 235000005152 nicotinamide Nutrition 0.000 description 7
• 239000011570 nicotinamide Substances 0.000 description 7
• 229960003966 nicotinamide Drugs 0.000 description 7
• 239000003921 oil Substances 0.000 description 7
• 235000019198 oils Nutrition 0.000 description 7
• 230000037361 pathway Effects 0.000 description 7
• 239000002953 phosphate buffered saline Substances 0.000 description 7
• 239000002244 precipitate Substances 0.000 description 7
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
• LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 7
• 230000002829 reductive effect Effects 0.000 description 7
• 239000007858 starting material Substances 0.000 description 7
• MKURCZPZTZGDIX-UHFFFAOYSA-N tert-butyl 3-(6-aminopyridine-3-carbonyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(C2)CCC1CN2C(=O)C1=CC=C(N)N=C1 MKURCZPZTZGDIX-UHFFFAOYSA-N 0.000 description 7
• SCTLMBLBWIVUFW-UHFFFAOYSA-N 2-(6-nitropyridin-3-yl)-3,4,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazin-1-one Chemical compound C1=NC([N+](=O)[O-])=CC=C1N1C(=O)C2CCCN2CC1 SCTLMBLBWIVUFW-UHFFFAOYSA-N 0.000 description 6
• HNTZKNJGAFJMHQ-UHFFFAOYSA-N 2-methylpyridine-3-carboxylic acid Chemical compound CC1=NC=CC=C1C(O)=O HNTZKNJGAFJMHQ-UHFFFAOYSA-N 0.000 description 6
• 102100032857 Cyclin-dependent kinase 1 Human genes 0.000 description 6
• 101710106279 Cyclin-dependent kinase 1 Proteins 0.000 description 6
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
• 208000034578 Multiple myelomas Diseases 0.000 description 6
• 206010035226 Plasma cell myeloma Diseases 0.000 description 6
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
• 230000004913 activation Effects 0.000 description 6
• HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 6
• 125000004432 carbon atom Chemical group C* 0.000 description 6
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
• 238000001816 cooling Methods 0.000 description 6
• 238000009472 formulation Methods 0.000 description 6
• 238000005227 gel permeation chromatography Methods 0.000 description 6
• 238000001727 in vivo Methods 0.000 description 6
• 230000002779 inactivation Effects 0.000 description 6
• 206010024627 liposarcoma Diseases 0.000 description 6
• 230000014759 maintenance of location Effects 0.000 description 6
• 230000035772 mutation Effects 0.000 description 6
• 230000002018 overexpression Effects 0.000 description 6
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
• 239000003039 volatile agent Substances 0.000 description 6
• FPIVTVPLBXUJRR-UHFFFAOYSA-N 2-(6-aminopyridin-3-yl)-3,4,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazin-1-one Chemical compound C1=NC(N)=CC=C1N1C(=O)C2CCCN2CC1 FPIVTVPLBXUJRR-UHFFFAOYSA-N 0.000 description 5
• BLJHSWAMPJGQPT-UHFFFAOYSA-N 2-chloro-7-cycloheptyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(Cl)N=C2N1C1CCCCCC1 BLJHSWAMPJGQPT-UHFFFAOYSA-N 0.000 description 5
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 5
• 102100024458 Cyclin-dependent kinase inhibitor 2A Human genes 0.000 description 5
• 208000000461 Esophageal Neoplasms Diseases 0.000 description 5
• 206010030155 Oesophageal carcinoma Diseases 0.000 description 5
• 206010042971 T-cell lymphoma Diseases 0.000 description 5
• 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 5
• 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 5
• 238000012512 characterization method Methods 0.000 description 5
• 239000003153 chemical reaction reagent Substances 0.000 description 5
• 229940127089 cytotoxic agent Drugs 0.000 description 5
• 238000001514 detection method Methods 0.000 description 5
• 238000005516 engineering process Methods 0.000 description 5
• 201000004101 esophageal cancer Diseases 0.000 description 5
• 238000001914 filtration Methods 0.000 description 5
• 230000004077 genetic alteration Effects 0.000 description 5
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 5
• 239000007937 lozenge Substances 0.000 description 5
• 239000011777 magnesium Substances 0.000 description 5
• 238000004519 manufacturing process Methods 0.000 description 5
• 230000003287 optical effect Effects 0.000 description 5
• IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 5
• 239000000843 powder Substances 0.000 description 5
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
• 210000003491 skin Anatomy 0.000 description 5
• 239000012453 solvate Substances 0.000 description 5
• 239000003826 tablet Substances 0.000 description 5
• RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical compound CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 description 5
• 238000012360 testing method Methods 0.000 description 5
• 230000005945 translocation Effects 0.000 description 5
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
• GYRXBFNBHPDFOA-KEVCNVLYSA-N 7-cycloheptyl-2-[[5-[(1r,5s)-9-hydroxy-3,7-diazabicyclo[3.3.1]nonane-3-carbonyl]pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@]1(CNC[C@@](C2)(C1O)[H])[H])N2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCCCC1 GYRXBFNBHPDFOA-KEVCNVLYSA-N 0.000 description 4
• OHOGKSHNJOSNJQ-BGYRXZFFSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-[(1r,5s)-3-oxa-7,9-diazabicyclo[3.3.1]nonane-9-carbonyl]pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1([C@]2([H])CNC[C@]1(COC2)[H])C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 OHOGKSHNJOSNJQ-BGYRXZFFSA-N 0.000 description 4
• 101150013553 CD40 gene Proteins 0.000 description 4
• 102100032937 CD40 ligand Human genes 0.000 description 4
• 229940124297 CDK 4/6 inhibitor Drugs 0.000 description 4
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
• 102000002427 Cyclin B Human genes 0.000 description 4
• 108010068150 Cyclin B Proteins 0.000 description 4
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 4
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
• 102000004190 Enzymes Human genes 0.000 description 4
• 108090000790 Enzymes Proteins 0.000 description 4
• 101000759376 Escherichia phage Mu Tail sheath protein Proteins 0.000 description 4
• 239000007995 HEPES buffer Substances 0.000 description 4
• 101000868215 Homo sapiens CD40 ligand Proteins 0.000 description 4
• NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 4
• 108091000080 Phosphotransferase Proteins 0.000 description 4
• 230000018199 S phase Effects 0.000 description 4
• 229910004298 SiO 2 Inorganic materials 0.000 description 4
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
• 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 4
• 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 4
• 230000002378 acidificating effect Effects 0.000 description 4
• 125000005907 alkyl ester group Chemical group 0.000 description 4
• 230000001028 anti-proliverative effect Effects 0.000 description 4
• 239000002246 antineoplastic agent Substances 0.000 description 4
• 239000008346 aqueous phase Substances 0.000 description 4
• 239000012298 atmosphere Substances 0.000 description 4
• 230000008901 benefit Effects 0.000 description 4
• DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 4
• 238000010790 dilution Methods 0.000 description 4
• 239000012895 dilution Substances 0.000 description 4
• SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Chemical group CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 4
• 208000035475 disorder Diseases 0.000 description 4
• 230000002255 enzymatic effect Effects 0.000 description 4
• NIHNNTQXNPWCJQ-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 4
• 125000001183 hydrocarbyl group Chemical group 0.000 description 4
• FGFUBBNNYLNVLJ-UHFFFAOYSA-N indol-3-one Chemical compound C1=CC=C2C(=O)C=NC2=C1 FGFUBBNNYLNVLJ-UHFFFAOYSA-N 0.000 description 4
• 230000002401 inhibitory effect Effects 0.000 description 4
• NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
• GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 4
• 230000007170 pathology Effects 0.000 description 4
• 102000020233 phosphotransferase Human genes 0.000 description 4
• 229910000027 potassium carbonate Inorganic materials 0.000 description 4
• 239000003755 preservative agent Substances 0.000 description 4
• 239000003381 stabilizer Substances 0.000 description 4
• 238000004808 supercritical fluid chromatography Methods 0.000 description 4
• IOGXIKSQPQGQJJ-UHFFFAOYSA-N tert-butyl 3-(6-aminopyridazine-3-carbonyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(C2)CCC1CN2C(=O)C1=CC=C(N)N=N1 IOGXIKSQPQGQJJ-UHFFFAOYSA-N 0.000 description 4
• FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 4
• OEQJOYQHIGIVTN-UHFFFAOYSA-N tert-butyl nonanoate Chemical compound CCCCCCCCC(=O)OC(C)(C)C OEQJOYQHIGIVTN-UHFFFAOYSA-N 0.000 description 4
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
• 230000001225 therapeutic effect Effects 0.000 description 4
• 210000001519 tissue Anatomy 0.000 description 4
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
• CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 4
• XKEPSNVFDIZRKX-UHFFFAOYSA-N (2-chloro-7-cycloheptylpyrrolo[2,3-d]pyrimidin-6-yl)methanol Chemical compound OCC1=CC2=CN=C(Cl)N=C2N1C1CCCCCC1 XKEPSNVFDIZRKX-UHFFFAOYSA-N 0.000 description 3
• LYVPWDUVRNOERF-UHFFFAOYSA-N 2-(6-nitropyridin-3-yl)-3,4,6,7,8,8a-hexahydro-1h-pyrrolo[1,2-a]pyrazine Chemical compound C1=NC([N+](=O)[O-])=CC=C1N1CC2CCCN2CC1 LYVPWDUVRNOERF-UHFFFAOYSA-N 0.000 description 3
• BRHFAHGYEGQNOI-UHFFFAOYSA-N 2-[[5-(3,4,6,7,8,8a-hexahydro-1h-pyrrolo[1,2-a]pyrazin-2-yl)pyridin-2-yl]amino]-7-cyclopentyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3CC4CCCN4CC3)N=C2N1C1CCCC1 BRHFAHGYEGQNOI-UHFFFAOYSA-N 0.000 description 3
• BXALLQBVYDONPU-ICSRJNTNSA-N 2-[[5-[(3as,7ar)-6-oxo-2,3,3a,4,7,7a-hexahydro-1h-pyrrolo[3,4-c]pyridin-5-yl]pyridin-2-yl]amino]-7-cycloheptyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(C[C@H]4CNC[C@H]4C3)=O)N=C2N1C1CCCCCC1 BXALLQBVYDONPU-ICSRJNTNSA-N 0.000 description 3
• OPXGIXNXHJHPLP-UHFFFAOYSA-N 3,8-diazabicyclo[3.2.1]octane-8-carboxylic acid Chemical compound C1NCC2CCC1N2C(=O)O OPXGIXNXHJHPLP-UHFFFAOYSA-N 0.000 description 3
• SQNHUZOPPRVLDH-UHFFFAOYSA-N 3-[2-chloro-4-(cycloheptylamino)pyrimidin-5-yl]prop-2-yn-1-ol Chemical compound OCC#CC1=CN=C(Cl)N=C1NC1CCCCCC1 SQNHUZOPPRVLDH-UHFFFAOYSA-N 0.000 description 3
• KDYZIBQFKOKQRM-MEKIYTOJSA-N 7-cycloheptyl-2-[[5-[(1r,4r,7r)-7-hydroxy-3-azabicyclo[2.2.1]heptane-3-carbonyl]pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1([C@]2([H])CC[C@@]([C@H]2O)(C1)[H])C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCCCC1 KDYZIBQFKOKQRM-MEKIYTOJSA-N 0.000 description 3
• IAKFUEXMEWDBAK-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=CN=C2NC(C(=O)N)=CC2=C1 IAKFUEXMEWDBAK-UHFFFAOYSA-N 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 3
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
• 206010009944 Colon cancer Diseases 0.000 description 3
• PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 3
• 238000002965 ELISA Methods 0.000 description 3
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
• ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical group NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 3
• 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 3
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
• 108091054455 MAP kinase family Proteins 0.000 description 3
• 102000043136 MAP kinase family Human genes 0.000 description 3
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical group [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 3
• 229920002472 Starch Polymers 0.000 description 3
• 239000006180 TBST buffer Substances 0.000 description 3
• 239000012317 TBTU Substances 0.000 description 3
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 3
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
• 102000004142 Trypsin Human genes 0.000 description 3
• 108090000631 Trypsin Proteins 0.000 description 3
• CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 3
• 238000010521 absorption reaction Methods 0.000 description 3
• 239000002671 adjuvant Substances 0.000 description 3
• 230000004075 alteration Effects 0.000 description 3
• 239000011575 calcium Substances 0.000 description 3
• 229910052791 calcium Inorganic materials 0.000 description 3
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
• 239000003054 catalyst Substances 0.000 description 3
• 230000022131 cell cycle Effects 0.000 description 3
• 239000013592 cell lysate Substances 0.000 description 3
• 230000004663 cell proliferation Effects 0.000 description 3
• 208000029742 colonic neoplasm Diseases 0.000 description 3
• 239000002254 cytotoxic agent Substances 0.000 description 3
• 239000000839 emulsion Substances 0.000 description 3
• 239000000284 extract Substances 0.000 description 3
• 239000000499 gel Substances 0.000 description 3
• 239000007903 gelatin capsule Substances 0.000 description 3
• 230000014509 gene expression Effects 0.000 description 3
• 125000005843 halogen group Chemical group 0.000 description 3
• 238000004128 high performance liquid chromatography Methods 0.000 description 3
• 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 description 3
• 239000008101 lactose Substances 0.000 description 3
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 3
• 239000000314 lubricant Substances 0.000 description 3
• 229910052749 magnesium Inorganic materials 0.000 description 3
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
• 235000019341 magnesium sulphate Nutrition 0.000 description 3
• 229960000485 methotrexate Drugs 0.000 description 3
• JACPDLJUQLKABC-UHFFFAOYSA-N methyl 6-aminopyridine-3-carboxylate Chemical compound COC(=O)C1=CC=C(N)N=C1 JACPDLJUQLKABC-UHFFFAOYSA-N 0.000 description 3
• SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 3
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
• 239000012074 organic phase Substances 0.000 description 3
• 229920001223 polyethylene glycol Polymers 0.000 description 3
• 229910052700 potassium Inorganic materials 0.000 description 3
• 108090000765 processed proteins & peptides Proteins 0.000 description 3
• 238000011160 research Methods 0.000 description 3
• 239000011780 sodium chloride Substances 0.000 description 3
• 125000003003 spiro group Chemical group 0.000 description 3
• 239000008107 starch Substances 0.000 description 3
• 235000019698 starch Nutrition 0.000 description 3
• 238000003860 storage Methods 0.000 description 3
• 208000024891 symptom Diseases 0.000 description 3
• 239000011975 tartaric acid Substances 0.000 description 3
• 235000002906 tartaric acid Nutrition 0.000 description 3
• IXKNPSLHUPHNQK-VXGBXAGGSA-N tert-butyl (1r,4r)-5-(6-aminopyridine-3-carbonyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C([C@@]1(N(C[C@@]2([H])C1)C(=O)OC(C)(C)C)[H])N2C(=O)C1=CC=C(N)N=C1 IXKNPSLHUPHNQK-VXGBXAGGSA-N 0.000 description 3
• YGTVAFAQOVALDB-UHFFFAOYSA-N tert-butyl 2-propyloctanoate Chemical compound CCCCCCC(CCC)C(=O)OC(C)(C)C YGTVAFAQOVALDB-UHFFFAOYSA-N 0.000 description 3
• VRAAJHHBWRUEPD-UHFFFAOYSA-N tert-butyl n-[3-(6-nitropyridin-3-yl)-3-azabicyclo[3.1.0]hexan-1-yl]carbamate Chemical compound C1C2(NC(=O)OC(C)(C)C)CC2CN1C1=CC=C([N+]([O-])=O)N=C1 VRAAJHHBWRUEPD-UHFFFAOYSA-N 0.000 description 3
• 239000012588 trypsin Substances 0.000 description 3
• 229960003048 vinblastine Drugs 0.000 description 3
• JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 3
• 238000005406 washing Methods 0.000 description 3
• YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
• MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 2
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
• FTTATHOUSOIFOQ-UHFFFAOYSA-N 1,2,3,4,6,7,8,8a-octahydropyrrolo[1,2-a]pyrazine Chemical compound C1NCCN2CCCC21 FTTATHOUSOIFOQ-UHFFFAOYSA-N 0.000 description 2
• LINDOXZENKYESA-UHFFFAOYSA-N 1,2-dimethylguanidine Chemical compound CNC(N)=NC LINDOXZENKYESA-UHFFFAOYSA-N 0.000 description 2
• BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 2
• AQUCDZZCANBRFO-UHFFFAOYSA-N 1-(3,8-diazabicyclo[3.2.1]octan-8-yl)ethanone Chemical compound C1NCC2CCC1N2C(=O)C AQUCDZZCANBRFO-UHFFFAOYSA-N 0.000 description 2
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• KKVYYGGCHJGEFJ-UHFFFAOYSA-N 1-n-(4-chlorophenyl)-6-methyl-5-n-[3-(7h-purin-6-yl)pyridin-2-yl]isoquinoline-1,5-diamine Chemical compound N=1C=CC2=C(NC=3C(=CC=CN=3)C=3C=4N=CNC=4N=CN=3)C(C)=CC=C2C=1NC1=CC=C(Cl)C=C1 KKVYYGGCHJGEFJ-UHFFFAOYSA-N 0.000 description 2
• 238000005160 1H NMR spectroscopy Methods 0.000 description 2
• OWQADRXHCRCSAM-UHFFFAOYSA-N 2-[4-[(5-bromo-2-chloropyrimidin-4-yl)amino]phenyl]-2-methylpropanenitrile Chemical compound C1=CC(C(C)(C#N)C)=CC=C1NC1=NC(Cl)=NC=C1Br OWQADRXHCRCSAM-UHFFFAOYSA-N 0.000 description 2
• DROFPQWMEFHUCZ-UHFFFAOYSA-N 2-[4-[[2-chloro-5-(3-hydroxyprop-1-ynyl)pyrimidin-4-yl]amino]phenyl]-2-methylpropanenitrile Chemical compound C1=CC(C(C)(C#N)C)=CC=C1NC1=NC(Cl)=NC=C1C#CCO DROFPQWMEFHUCZ-UHFFFAOYSA-N 0.000 description 2
• NFNVBMMKAPKBEG-UHFFFAOYSA-N 2-chloro-7-cyclohexyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(Cl)N=C2N1C1CCCCC1 NFNVBMMKAPKBEG-UHFFFAOYSA-N 0.000 description 2
• IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
• JBIHMFNMKHDTEE-UHFFFAOYSA-N 3,4,6,7,8,8a-hexahydro-2h-pyrrolo[1,2-a]pyrazin-1-one Chemical compound O=C1NCCN2CCCC12 JBIHMFNMKHDTEE-UHFFFAOYSA-N 0.000 description 2
• NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 2
• GANOSODRVKCPCV-UHFFFAOYSA-N 3-(6-aminopyridine-3-carbonyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylic acid Chemical compound NC1=CC=C(C=N1)C(=O)N1CC2CCC(C1)N2C(=O)O GANOSODRVKCPCV-UHFFFAOYSA-N 0.000 description 2
• TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 2
• IKMVALRMRGIPIJ-UHFFFAOYSA-N 5-(3,4,6,7,8,8a-hexahydro-1h-pyrrolo[1,2-a]pyrazin-2-yl)pyridin-2-amine Chemical compound C1=NC(N)=CC=C1N1CC2CCCN2CC1 IKMVALRMRGIPIJ-UHFFFAOYSA-N 0.000 description 2
• SIKXIUWKPGWBBF-UHFFFAOYSA-N 5-bromo-2,4-dichloropyrimidine Chemical compound ClC1=NC=C(Br)C(Cl)=N1 SIKXIUWKPGWBBF-UHFFFAOYSA-N 0.000 description 2
• OTXZCRCTNZCHKJ-UHFFFAOYSA-N 6-aminopyridazine-3-carboxylic acid Chemical compound NC1=CC=C(C(O)=O)N=N1 OTXZCRCTNZCHKJ-UHFFFAOYSA-N 0.000 description 2
• 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 2
• BNXVQCFHGPTGJT-UHFFFAOYSA-N 7-cycloheptyl-2-[[5-(3,8-diazabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4)C3)N=C2N1C1CCCCCC1 BNXVQCFHGPTGJT-UHFFFAOYSA-N 0.000 description 2
• WCKGPGTXDGDKMB-UHFFFAOYSA-N 7-cycloheptyl-2-[[5-(8-hydroxy-8-methyl-3-azabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(C4(C)O)C3)N=C2N1C1CCCCCC1 WCKGPGTXDGDKMB-UHFFFAOYSA-N 0.000 description 2
• HYLVNBXAOJUSTK-UHFFFAOYSA-N 7-cyclopentyl-2-[[5-(2,6-diazaspiro[3.3]heptane-2-carbonyl)pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=C2N(C3CCCC3)C(C(=O)N(C)C)=CC2=CN=C1NC(N=C1)=CC=C1C(=O)N(C1)CC21CNC2 HYLVNBXAOJUSTK-UHFFFAOYSA-N 0.000 description 2
• DGHUARQKUGEORR-HFSMHLIXSA-N 7-cyclopentyl-2-[[5-[(1s,4s,5r)-5-hydroxy-2-azabicyclo[2.2.1]heptane-2-carbonyl]pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@]1([C@@H](C[C@]2([H])C1)O)[H])N2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 DGHUARQKUGEORR-HFSMHLIXSA-N 0.000 description 2
• DGHUARQKUGEORR-CUWPLCDZSA-N 7-cyclopentyl-2-[[5-[(1s,4s,5s)-5-hydroxy-2-azabicyclo[2.2.1]heptane-2-carbonyl]pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@]1([C@H](C[C@]2([H])C1)O)[H])N2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 DGHUARQKUGEORR-CUWPLCDZSA-N 0.000 description 2
• GIGBBCAIXDPDLD-LIMIJEPZSA-N 7-cyclopentyl-2-[[5-[(1s,5r)-9-hydroxy-3,7-diazabicyclo[3.3.1]nonane-3-carbonyl]pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound C([C@]1(CNC[C@@](C2)(C1O)[H])[H])N2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 GIGBBCAIXDPDLD-LIMIJEPZSA-N 0.000 description 2
• MUTDVTPBZIPMQD-UHFFFAOYSA-N 7-cyclopentyl-2-[[5-[8-(dimethylamino)-3-azabicyclo[3.2.1]octane-3-carbonyl]pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C1C(C2)CCC1CN2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 MUTDVTPBZIPMQD-UHFFFAOYSA-N 0.000 description 2
• LKIMOMLBYIKHGV-UHFFFAOYSA-N 7-cyclopentyl-n,n-dimethyl-2-[[5-(8-propan-2-yl-3,8-diazabicyclo[3.2.1]octane-3-carbonyl)pyridin-2-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CC(C)N1C(C2)CCC1CN2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 LKIMOMLBYIKHGV-UHFFFAOYSA-N 0.000 description 2
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 2
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 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
• 201000001320 Atherosclerosis Diseases 0.000 description 2
• GVBKVMRXNMOBSG-HZPDHXFCSA-N C([C@@H]1CCN([C@@H]1C1)C(=O)O)CCN1CCC1=CC=CC=C1 Chemical compound C([C@@H]1CCN([C@@H]1C1)C(=O)O)CCN1CCC1=CC=CC=C1 GVBKVMRXNMOBSG-HZPDHXFCSA-N 0.000 description 2
• PETJEGONRNJOSC-UHFFFAOYSA-N CC(C)(C)OC(=O)N1C2CC(C1C3=CN=C(C=C3)N)NC2 Chemical compound CC(C)(C)OC(=O)N1C2CC(C1C3=CN=C(C=C3)N)NC2 PETJEGONRNJOSC-UHFFFAOYSA-N 0.000 description 2
• 101150108519 CDK4 gene Proteins 0.000 description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
• 241000282472 Canis lupus familiaris Species 0.000 description 2
• 201000009030 Carcinoma Diseases 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• 108010058545 Cyclin D3 Proteins 0.000 description 2
• 229940093444 Cyclooxygenase 2 inhibitor Drugs 0.000 description 2
• 229930105110 Cyclosporin A Natural products 0.000 description 2
• 108010036949 Cyclosporine Proteins 0.000 description 2
• UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 2
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 2
• 101150029707 ERBB2 gene Proteins 0.000 description 2
• ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• XPDWGBQVDMORPB-UHFFFAOYSA-N Fluoroform Chemical compound FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 description 2
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
• 102100037859 G1/S-specific cyclin-D3 Human genes 0.000 description 2
• 101710113436 GTPase KRas Proteins 0.000 description 2
• 241000237858 Gastropoda Species 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• 108010009202 Growth Factor Receptors Proteins 0.000 description 2
• 102000009465 Growth Factor Receptors Human genes 0.000 description 2
• 239000007821 HATU Substances 0.000 description 2
• 102000006947 Histones Human genes 0.000 description 2
• 108010033040 Histones Proteins 0.000 description 2
• 101000932478 Homo sapiens Receptor-type tyrosine-protein kinase FLT3 Proteins 0.000 description 2
• 239000005909 Kieselgur Substances 0.000 description 2
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
• 206010025323 Lymphomas Diseases 0.000 description 2
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
• 241000124008 Mammalia Species 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• 101100381978 Mus musculus Braf gene Proteins 0.000 description 2
• 201000003793 Myelodysplastic syndrome Diseases 0.000 description 2
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 2
• CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Chemical group CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 2
• 108010057466 NF-kappa B Proteins 0.000 description 2
• 102000003945 NF-kappa B Human genes 0.000 description 2
• 108700020796 Oncogene Proteins 0.000 description 2
• 229930012538 Paclitaxel Natural products 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• 239000004793 Polystyrene Substances 0.000 description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
• 241000288906 Primates Species 0.000 description 2
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 2
• 241000700159 Rattus Species 0.000 description 2
• 102100020718 Receptor-type tyrosine-protein kinase FLT3 Human genes 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
• 235000021355 Stearic acid Nutrition 0.000 description 2
• 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 2
• 108050003627 Wnt Proteins 0.000 description 2
• 102000013814 Wnt Human genes 0.000 description 2
• 230000002159 abnormal effect Effects 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 230000003213 activating effect Effects 0.000 description 2
• 125000002252 acyl group Chemical group 0.000 description 2
• 239000000443 aerosol Substances 0.000 description 2
• 239000000783 alginic acid Substances 0.000 description 2
• 235000010443 alginic acid Nutrition 0.000 description 2
• 229920000615 alginic acid Polymers 0.000 description 2
• 229960001126 alginic acid Drugs 0.000 description 2
• 150000004781 alginic acids Chemical class 0.000 description 2
• 239000003513 alkali Substances 0.000 description 2
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
• 229960003896 aminopterin Drugs 0.000 description 2
• 239000002260 anti-inflammatory agent Substances 0.000 description 2
• 229940121363 anti-inflammatory agent Drugs 0.000 description 2
• VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 2
• UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
• 125000002619 bicyclic group Chemical class 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 201000000053 blastoma Diseases 0.000 description 2
• 210000000481 breast Anatomy 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• 229910000019 calcium carbonate Inorganic materials 0.000 description 2
• 239000001506 calcium phosphate Substances 0.000 description 2
• 229910000389 calcium phosphate Inorganic materials 0.000 description 2
• 235000011010 calcium phosphates Nutrition 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 150000001721 carbon Chemical group 0.000 description 2
• 229960004562 carboplatin Drugs 0.000 description 2
• 230000015556 catabolic process Effects 0.000 description 2
• 238000004113 cell culture Methods 0.000 description 2
• 239000013553 cell monolayer Substances 0.000 description 2
• 239000006285 cell suspension Substances 0.000 description 2
• 230000001413 cellular effect Effects 0.000 description 2
• 230000005754 cellular signaling Effects 0.000 description 2
• WGXZDYPGLJYBJW-UHFFFAOYSA-N chloroform;propan-2-ol Chemical compound CC(C)O.ClC(Cl)Cl WGXZDYPGLJYBJW-UHFFFAOYSA-N 0.000 description 2
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 2
• 229960004316 cisplatin Drugs 0.000 description 2
• 235000015165 citric acid Nutrition 0.000 description 2
• 239000003086 colorant Substances 0.000 description 2
• 238000002648 combination therapy Methods 0.000 description 2
• 239000013058 crude material Substances 0.000 description 2
• 239000013078 crystal Substances 0.000 description 2
• 238000002425 crystallisation Methods 0.000 description 2
• 230000008025 crystallization Effects 0.000 description 2
• 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 2
• 231100000599 cytotoxic agent Toxicity 0.000 description 2
• 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 2
• 229960000975 daunorubicin Drugs 0.000 description 2
• 238000006731 degradation reaction Methods 0.000 description 2
• NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• 239000013024 dilution buffer Substances 0.000 description 2
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 230000007831 electrophysiology Effects 0.000 description 2
• 238000002001 electrophysiology Methods 0.000 description 2
• 201000008184 embryoma Diseases 0.000 description 2
• 239000003995 emulsifying agent Substances 0.000 description 2
• 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 2
• 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 2
• YJGVMLPVUAXIQN-UHFFFAOYSA-N epipodophyllotoxin Natural products COC1=C(OC)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YJGVMLPVUAXIQN-UHFFFAOYSA-N 0.000 description 2
• 229930013356 epothilone Natural products 0.000 description 2
• 150000003883 epothilone derivatives Chemical class 0.000 description 2
• 210000003238 esophagus Anatomy 0.000 description 2
• DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 2
• UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 2
• DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 229960005420 etoposide Drugs 0.000 description 2
• 229960000752 etoposide phosphate Drugs 0.000 description 2
• LIQODXNTTZAGID-OCBXBXKTSA-N etoposide phosphate Chemical compound COC1=C(OP(O)(O)=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 LIQODXNTTZAGID-OCBXBXKTSA-N 0.000 description 2
• 238000000605 extraction Methods 0.000 description 2
• 239000000796 flavoring agent Substances 0.000 description 2
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 2
• 229910052731 fluorine Inorganic materials 0.000 description 2
• 239000011737 fluorine Substances 0.000 description 2
• 125000001153 fluoro group Chemical group F* 0.000 description 2
• 229960002949 fluorouracil Drugs 0.000 description 2
• 239000011888 foil Substances 0.000 description 2
• 235000013355 food flavoring agent Nutrition 0.000 description 2
• 235000003599 food sweetener Nutrition 0.000 description 2
• 239000012458 free base Substances 0.000 description 2
• 108020001507 fusion proteins Proteins 0.000 description 2
• 102000037865 fusion proteins Human genes 0.000 description 2
• 239000008273 gelatin Substances 0.000 description 2
• 229920000159 gelatin Polymers 0.000 description 2
• 235000019322 gelatine Nutrition 0.000 description 2
• 235000011852 gelatine desserts Nutrition 0.000 description 2
• SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 2
• 229960005277 gemcitabine Drugs 0.000 description 2
• BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 2
• 150000002344 gold compounds Chemical class 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 230000012010 growth Effects 0.000 description 2
• 229940093915 gynecological organic acid Drugs 0.000 description 2
• 125000001188 haloalkyl group Chemical group 0.000 description 2
• 201000005787 hematologic cancer Diseases 0.000 description 2
• 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 2
• 150000004677 hydrates Chemical class 0.000 description 2
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
• XLSMFKSTNGKWQX-UHFFFAOYSA-N hydroxyacetone Chemical compound CC(=O)CO XLSMFKSTNGKWQX-UHFFFAOYSA-N 0.000 description 2
• 239000003018 immunosuppressive agent Substances 0.000 description 2
• 238000000338 in vitro Methods 0.000 description 2
• UTWGRMYWDUMKNY-UHFFFAOYSA-N indole-1-carboxylic acid Chemical compound C1=CC=C2N(C(=O)O)C=CC2=C1 UTWGRMYWDUMKNY-UHFFFAOYSA-N 0.000 description 2
• 239000003701 inert diluent Substances 0.000 description 2
• 150000007529 inorganic bases Chemical class 0.000 description 2
• 230000003993 interaction Effects 0.000 description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• 229940043355 kinase inhibitor Drugs 0.000 description 2
• 230000000670 limiting effect Effects 0.000 description 2
• 229940124302 mTOR inhibitor Drugs 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
• BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
• 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 description 2
• 229960001428 mercaptopurine Drugs 0.000 description 2
• 230000002503 metabolic effect Effects 0.000 description 2
• 230000004060 metabolic process Effects 0.000 description 2
• 229910052751 metal Inorganic materials 0.000 description 2
• 239000002184 metal Substances 0.000 description 2
• OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 229960004857 mitomycin Drugs 0.000 description 2
• 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
• 125000002950 monocyclic group Chemical class 0.000 description 2
• RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 description 2
• 229960004866 mycophenolate mofetil Drugs 0.000 description 2
• YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 2
• 239000006199 nebulizer Substances 0.000 description 2
• 201000008383 nephritis Diseases 0.000 description 2
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• 150000007530 organic bases Chemical class 0.000 description 2
• 229960001592 paclitaxel Drugs 0.000 description 2
• NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 2
• 230000001575 pathological effect Effects 0.000 description 2
• 239000008188 pellet Substances 0.000 description 2
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 2
• 229960001237 podophyllotoxin Drugs 0.000 description 2
• YJGVMLPVUAXIQN-XVVDYKMHSA-N podophyllotoxin Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-XVVDYKMHSA-N 0.000 description 2
• YVCVYCSAAZQOJI-UHFFFAOYSA-N podophyllotoxin Natural products COC1=C(O)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YVCVYCSAAZQOJI-UHFFFAOYSA-N 0.000 description 2
• 238000002600 positron emission tomography Methods 0.000 description 2
• 239000011591 potassium Substances 0.000 description 2
• 230000002265 prevention Effects 0.000 description 2
• 230000008569 process Effects 0.000 description 2
• TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 2
• 238000010926 purge Methods 0.000 description 2
• ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 2
• 239000011535 reaction buffer Substances 0.000 description 2
• 108020003175 receptors Proteins 0.000 description 2
• 102000005962 receptors Human genes 0.000 description 2
• 238000001953 recrystallisation Methods 0.000 description 2
• 238000010992 reflux Methods 0.000 description 2
• 230000004044 response Effects 0.000 description 2
• 230000002207 retinal effect Effects 0.000 description 2
• 238000010079 rubber tapping Methods 0.000 description 2
• 229910052707 ruthenium Inorganic materials 0.000 description 2
• 238000013207 serial dilution Methods 0.000 description 2
• 239000000741 silica gel Substances 0.000 description 2
• 229910002027 silica gel Inorganic materials 0.000 description 2
• 238000002603 single-photon emission computed tomography Methods 0.000 description 2
• QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 2
• 229960002930 sirolimus Drugs 0.000 description 2
• 150000003384 small molecules Chemical class 0.000 description 2
• PNGLEYLFMHGIQO-UHFFFAOYSA-M sodium;3-(n-ethyl-3-methoxyanilino)-2-hydroxypropane-1-sulfonate;dihydrate Chemical compound O.O.[Na+].[O-]S(=O)(=O)CC(O)CN(CC)C1=CC=CC(OC)=C1 PNGLEYLFMHGIQO-UHFFFAOYSA-M 0.000 description 2
• 238000003797 solvolysis reaction Methods 0.000 description 2
• 239000007921 spray Substances 0.000 description 2
• 239000008117 stearic acid Substances 0.000 description 2
• 150000003431 steroids Chemical class 0.000 description 2
• UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
• 229960005322 streptomycin Drugs 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 230000002459 sustained effect Effects 0.000 description 2
• 239000003765 sweetening agent Substances 0.000 description 2
• 230000002195 synergetic effect Effects 0.000 description 2
• 239000000454 talc Substances 0.000 description 2
• 235000012222 talc Nutrition 0.000 description 2
• 229910052623 talc Inorganic materials 0.000 description 2
• 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 2
• 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 2
• 229960001278 teniposide Drugs 0.000 description 2
• NXIZCOXUZZYOOJ-ULKQDVFKSA-N tert-butyl (1r,5s)-9-hydroxy-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1NC[C@]2([H])CN(C(=O)OC(C)(C)C)C[C@@]1([H])C2O NXIZCOXUZZYOOJ-ULKQDVFKSA-N 0.000 description 2
• FYUVLZRRIRGSTE-UHFFFAOYSA-N tert-butyl 2,3,3a,4,6,6a-hexahydro-1h-pyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound C1NCC2CN(C(=O)OC(C)(C)C)CC21 FYUVLZRRIRGSTE-UHFFFAOYSA-N 0.000 description 2
• UXAWXZDXVOYLII-UHFFFAOYSA-N tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C1C2N(C(=O)OC(C)(C)C)CC1NC2 UXAWXZDXVOYLII-UHFFFAOYSA-N 0.000 description 2
• PSHHHKJQKVFITC-UHFFFAOYSA-N tert-butyl 2-(6-aminopyridin-3-yl)-3-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC11CC(=O)N(C=2C=NC(N)=CC=2)C1 PSHHHKJQKVFITC-UHFFFAOYSA-N 0.000 description 2
• VULHROMOFQYLNP-UHFFFAOYSA-N tert-butyl 2-methyldecanoate Chemical compound CCCCCCCCC(C)C(=O)OC(C)(C)C VULHROMOFQYLNP-UHFFFAOYSA-N 0.000 description 2
• XBZRKFUZAISVQF-UHFFFAOYSA-N tert-butyl 2-propylnonanoate Chemical compound C(C)(C)(C)OC(=O)C(CCC)CCCCCCC XBZRKFUZAISVQF-UHFFFAOYSA-N 0.000 description 2
• IZLGOGRHBJIRNU-UHFFFAOYSA-N tert-butyl 3,9-diazabicyclo[3.3.1]nonane-9-carboxylate Chemical compound C1CCC2CNCC1N2C(=O)OC(C)(C)C IZLGOGRHBJIRNU-UHFFFAOYSA-N 0.000 description 2
• BAWOGNNTLNPQKC-UHFFFAOYSA-N tert-butyl 3-(6-amino-2-methylpyridine-3-carbonyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CC1=NC(N)=CC=C1C(=O)N1CC(N2C(=O)OC(C)(C)C)CCC2C1 BAWOGNNTLNPQKC-UHFFFAOYSA-N 0.000 description 2
• RLFUBOGBOXTLSZ-UHFFFAOYSA-N tert-butyl 3-(6-amino-4-methylpyridine-3-carbonyl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CC1=CC(N)=NC=C1C(=O)N1CC(N2C(=O)OC(C)(C)C)CCC2C1 RLFUBOGBOXTLSZ-UHFFFAOYSA-N 0.000 description 2
• MBKGDJKXYKTWSP-UHFFFAOYSA-N tert-butyl 3-(6-aminopyridin-3-yl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(C2)CCC1CN2C1=CC=C(N)N=C1 MBKGDJKXYKTWSP-UHFFFAOYSA-N 0.000 description 2
• RDVDMXBLFVLYIR-UHFFFAOYSA-N tert-butyl 3-(6-aminopyridine-3-carbonyl)-3,9-diazabicyclo[3.3.1]nonane-9-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(C2)CCCC1CN2C(=O)C1=CC=C(N)N=C1 RDVDMXBLFVLYIR-UHFFFAOYSA-N 0.000 description 2
• JSNNSBUDVLWJNA-UHFFFAOYSA-N tert-butyl 3-(6-nitropyridin-3-yl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(C2)CCC1CN2C1=CC=C([N+]([O-])=O)N=C1 JSNNSBUDVLWJNA-UHFFFAOYSA-N 0.000 description 2
• NLQYXKVXZFENMF-UHFFFAOYSA-N tert-butyl 4-(6-aminopyridin-3-yl)-3-oxo-8-oxa-4,10-diazabicyclo[4.3.1]decane-10-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(C2)COCC1CC(=O)N2C1=CC=C(N)N=C1 NLQYXKVXZFENMF-UHFFFAOYSA-N 0.000 description 2
• GGHIWYYHMKZSRN-UHFFFAOYSA-N tert-butyl 4-(6-nitropyridin-3-yl)-3-oxo-4,9-diazabicyclo[4.2.1]nonane-9-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(C2)CCC1CC(=O)N2C1=CC=C([N+]([O-])=O)N=C1 GGHIWYYHMKZSRN-UHFFFAOYSA-N 0.000 description 2
• IJHTZGBRXSYOMG-UHFFFAOYSA-N tert-butyl n-(3-azabicyclo[3.1.0]hexan-1-yl)carbamate Chemical compound C1NCC2(NC(=O)OC(C)(C)C)C1C2 IJHTZGBRXSYOMG-UHFFFAOYSA-N 0.000 description 2
• YSQUMWRBEUYICX-UHFFFAOYSA-N tert-butyl n-[3-(6-aminopyridin-3-yl)-3-azabicyclo[3.1.0]hexan-1-yl]carbamate Chemical compound C1C2(NC(=O)OC(C)(C)C)CC2CN1C1=CC=C(N)N=C1 YSQUMWRBEUYICX-UHFFFAOYSA-N 0.000 description 2
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 2
• ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
• 238000002560 therapeutic procedure Methods 0.000 description 2
• 208000030901 thyroid gland follicular carcinoma Diseases 0.000 description 2
• 238000011200 topical administration Methods 0.000 description 2
• 230000000699 topical effect Effects 0.000 description 2
• 230000007704 transition Effects 0.000 description 2
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
• 229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 description 2
• 239000002452 tumor necrosis factor alpha inhibitor Substances 0.000 description 2
• 102000003298 tumor necrosis factor receptor Human genes 0.000 description 2
• 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 2
• 229960004528 vincristine Drugs 0.000 description 2
• 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 2
• HHJUWIANJFBDHT-KOTLKJBCSA-N vindesine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(N)=O)N4C)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 HHJUWIANJFBDHT-KOTLKJBCSA-N 0.000 description 2
• 229960004355 vindesine Drugs 0.000 description 2
• 239000011534 wash buffer Substances 0.000 description 2
• 239000000080 wetting agent Substances 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
• UKHJNJFJCGBKSF-RFZPGFLSSA-N (1r,4r)-2,5-diazabicyclo[2.2.1]heptane Chemical compound C1N[C@@]2([H])CN[C@]1([H])C2 UKHJNJFJCGBKSF-RFZPGFLSSA-N 0.000 description 1
• OZFAFGSSMRRTDW-UHFFFAOYSA-N (2,4-dichlorophenyl) benzenesulfonate Chemical compound ClC1=CC(Cl)=CC=C1OS(=O)(=O)C1=CC=CC=C1 OZFAFGSSMRRTDW-UHFFFAOYSA-N 0.000 description 1
• UIJJGKYDYHGDPG-UHFFFAOYSA-N (2-chloro-7-cyclohexylpyrrolo[2,3-d]pyrimidin-6-yl)methanol Chemical compound OCC1=CC2=CN=C(Cl)N=C2N1C1CCCCC1 UIJJGKYDYHGDPG-UHFFFAOYSA-N 0.000 description 1
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
• ZQEBQGAAWMOMAI-SSDOTTSWSA-N (2r)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCC[C@@H]1C(O)=O ZQEBQGAAWMOMAI-SSDOTTSWSA-N 0.000 description 1
• IMUSLIHRIYOHEV-SSDOTTSWSA-N (2r)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-4-methylsulfanylbutanoic acid Chemical compound CSCC[C@H](C(O)=O)NC(=O)OC(C)(C)C IMUSLIHRIYOHEV-SSDOTTSWSA-N 0.000 description 1
• ZQEBQGAAWMOMAI-ZETCQYMHSA-N (2s)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCC[C@H]1C(O)=O ZQEBQGAAWMOMAI-ZETCQYMHSA-N 0.000 description 1
• YIJOVTRYJSZXBD-HTQZYQBOSA-N (3aR,8aS)-3,3a,4,5,6,7,8,8a-octahydro-2H-pyrrolo[2,3-c]azepine-1-carboxylic acid Chemical compound N1(CC[C@@H]2[C@H]1CNCCC2)C(=O)O YIJOVTRYJSZXBD-HTQZYQBOSA-N 0.000 description 1
• HIJHWAJALGSHLA-HZPDHXFCSA-N (3ar,8as)-7-(2-phenylethyl)-2,3,3a,4,5,6,8,8a-octahydro-1h-pyrrolo[2,3-c]azepine Chemical compound C([C@H]1NCC[C@H]1CCC1)N1CCC1=CC=CC=C1 HIJHWAJALGSHLA-HZPDHXFCSA-N 0.000 description 1
• FTTATHOUSOIFOQ-SSDOTTSWSA-N (8ar)-1,2,3,4,6,7,8,8a-octahydropyrrolo[1,2-a]pyrazine Chemical compound C1NCCN2CCC[C@@H]21 FTTATHOUSOIFOQ-SSDOTTSWSA-N 0.000 description 1
• DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
• DIIIISSCIXVANO-UHFFFAOYSA-N 1,2-Dimethylhydrazine Chemical compound CNNC DIIIISSCIXVANO-UHFFFAOYSA-N 0.000 description 1
• CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 1
• VCIKVHACZDLJCT-UHFFFAOYSA-N 1,4-diazabicyclo[3.2.2]nonan-3-one Chemical compound N1C(=O)CN2CCC1CC2 VCIKVHACZDLJCT-UHFFFAOYSA-N 0.000 description 1
• ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
• WWIKWOJUJQCHIZ-UHFFFAOYSA-N 1-methyl-9h-xanthene Chemical compound O1C2=CC=CC=C2CC2=C1C=CC=C2C WWIKWOJUJQCHIZ-UHFFFAOYSA-N 0.000 description 1
• LNETULKMXZVUST-UHFFFAOYSA-N 1-naphthoic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-N 0.000 description 1
• RTMMSCJWQYWMNK-UHFFFAOYSA-N 2,2,2-trifluoroethyl trifluoromethanesulfonate Chemical compound FC(F)(F)COS(=O)(=O)C(F)(F)F RTMMSCJWQYWMNK-UHFFFAOYSA-N 0.000 description 1
• CPLWWXZZFYHPJY-UHFFFAOYSA-N 2,3-dihydroxy-2,3-dimethylbutanedioic acid Chemical compound OC(=O)C(O)(C)C(C)(O)C(O)=O CPLWWXZZFYHPJY-UHFFFAOYSA-N 0.000 description 1
• ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 description 1
• FUPZCCAUPTZBGB-UHFFFAOYSA-N 2-(3,8-diazabicyclo[3.2.1]octan-8-yl)ethanol Chemical compound C1NCC2CCC1N2CCO FUPZCCAUPTZBGB-UHFFFAOYSA-N 0.000 description 1
• VXDPOGVDHHJTDY-UHFFFAOYSA-N 2-(4-aminophenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)C1=CC=C(N)C=C1 VXDPOGVDHHJTDY-UHFFFAOYSA-N 0.000 description 1
• LQPPBDSKWIFZOF-UHFFFAOYSA-N 2-(6-aminopyridin-3-yl)-4,6,7,8,9,9a-hexahydro-3h-pyrido[1,2-a]pyrazin-1-one Chemical compound C1=NC(N)=CC=C1N1C(=O)C2CCCCN2CC1 LQPPBDSKWIFZOF-UHFFFAOYSA-N 0.000 description 1
• VGYKPHATGIGNLP-UHFFFAOYSA-N 2-(6-nitropyridin-3-yl)-1-oxo-2,9-diazaspiro[5.5]undecane-9-carboxylic acid Chemical compound [N+](=O)([O-])C1=CC=C(C=N1)N1C(C2(CCC1)CCN(CC2)C(=O)O)=O VGYKPHATGIGNLP-UHFFFAOYSA-N 0.000 description 1
• LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
• NKBWMBRPILTCRD-UHFFFAOYSA-N 2-Methylheptanoic acid Chemical compound CCCCCC(C)C(O)=O NKBWMBRPILTCRD-UHFFFAOYSA-N 0.000 description 1
• VRPJIFMKZZEXLR-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical compound CC(C)(C)OC(=O)NCC(O)=O VRPJIFMKZZEXLR-UHFFFAOYSA-N 0.000 description 1
• HWMBWZMRKAEGHV-UHFFFAOYSA-N 2-[4-[2-chloro-6-(hydroxymethyl)pyrrolo[2,3-d]pyrimidin-7-yl]phenyl]-2-methylpropanenitrile Chemical compound C1=CC(C(C)(C#N)C)=CC=C1N1C2=NC(Cl)=NC=C2C=C1CO HWMBWZMRKAEGHV-UHFFFAOYSA-N 0.000 description 1
• GOBAXMJYGDOAFA-UHFFFAOYSA-N 2-[[5-(2,3,3a,4,6,6a-hexahydro-1h-pyrrolo[3,4-c]pyrrole-5-carbonyl)pyridin-2-yl]amino]-7-cyclopentyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CNCC4C3)N=C2N1C1CCCC1 GOBAXMJYGDOAFA-UHFFFAOYSA-N 0.000 description 1
• QHKSOUNRROAMGU-SFTDATJTSA-N 2-[[5-[(3as,7ar)-2-methyl-6-oxo-1,3,3a,4,7,7a-hexahydropyrrolo[3,4-c]pyridin-5-yl]pyridin-2-yl]amino]-7-cycloheptyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)N3C(C[C@H]4CN(C)C[C@H]4C3)=O)N=C2N1C1CCCCCC1 QHKSOUNRROAMGU-SFTDATJTSA-N 0.000 description 1
• WXHLLJAMBQLULT-UHFFFAOYSA-N 2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-n-(2-methyl-6-sulfanylphenyl)-1,3-thiazole-5-carboxamide;hydrate Chemical compound O.C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1S WXHLLJAMBQLULT-UHFFFAOYSA-N 0.000 description 1
• KPIVDNYJNOPGBE-UHFFFAOYSA-N 2-aminonicotinic acid Chemical compound NC1=NC=CC=C1C(O)=O KPIVDNYJNOPGBE-UHFFFAOYSA-N 0.000 description 1
• HUUFTVUBFFESEN-UHFFFAOYSA-N 2-bromo-5-nitropyridine Chemical compound [O-][N+](=O)C1=CC=C(Br)N=C1 HUUFTVUBFFESEN-UHFFFAOYSA-N 0.000 description 1
• PSQCBIKUVQQSOV-UHFFFAOYSA-N 2-chloro-7-[4-(2-cyanopropan-2-yl)phenyl]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(Cl)N=C2N1C1=CC=C(C(C)(C)C#N)C=C1 PSQCBIKUVQQSOV-UHFFFAOYSA-N 0.000 description 1
• HUJZYYLVDRDEEX-UHFFFAOYSA-N 2-chloro-7-cyclobutyl-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(Cl)N=C2N1C1CCC1 HUJZYYLVDRDEEX-UHFFFAOYSA-N 0.000 description 1
• JATZKXQRAAGTGK-UHFFFAOYSA-N 2-chloro-7-cyclopentyl-n-methylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CNC(=O)C1=CC2=CN=C(Cl)N=C2N1C1CCCC1 JATZKXQRAAGTGK-UHFFFAOYSA-N 0.000 description 1
• LXCZVGKSFJMLRO-UHFFFAOYSA-N 2-chloro-7-cyclopentylpyrrolo[2,3-d]pyrimidine-6-carboxylic acid Chemical compound OC(=O)C1=CC2=CN=C(Cl)N=C2N1C1CCCC1 LXCZVGKSFJMLRO-UHFFFAOYSA-N 0.000 description 1
• NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 1
• BFJSDDYECHPBIO-UHFFFAOYSA-N 2-hydroxybenzoic acid;sulfuric acid Chemical compound OS(O)(=O)=O.OC(=O)C1=CC=CC=C1O BFJSDDYECHPBIO-UHFFFAOYSA-N 0.000 description 1
• OQHQOOLVQDEIGL-UHFFFAOYSA-N 2-methyl-2,7-diazaspiro[4.4]nonane Chemical compound C1N(C)CCC11CNCC1 OQHQOOLVQDEIGL-UHFFFAOYSA-N 0.000 description 1
• 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
• 125000005916 2-methylpentyl group Chemical group 0.000 description 1
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• DTXVKPOKPFWSFF-UHFFFAOYSA-N 3(S)-hydroxy-13-cis-eicosenoyl-CoA Chemical compound NC1=CC=C(Cl)N=N1 DTXVKPOKPFWSFF-UHFFFAOYSA-N 0.000 description 1
• VQAFMTSSCUETHA-UHFFFAOYSA-N 3,6-dibromopyridazine Chemical compound BrC1=CC=C(Br)N=N1 VQAFMTSSCUETHA-UHFFFAOYSA-N 0.000 description 1
• HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
• RNHNJPYGHWXTSE-UHFFFAOYSA-N 3-(2-phenylethyl)-9-oxa-3,7-diazabicyclo[3.3.1]nonane Chemical compound C1C(O2)CNCC2CN1CCC1=CC=CC=C1 RNHNJPYGHWXTSE-UHFFFAOYSA-N 0.000 description 1
• BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
• CUOLNTQHCSUATC-UHFFFAOYSA-N 3-(6-aminopyridin-3-yl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylic acid Chemical compound NC1=CC=C(C=N1)N1CC2CCC(C1)N2C(=O)O CUOLNTQHCSUATC-UHFFFAOYSA-N 0.000 description 1
• FQFWFNZKDPSDPX-UHFFFAOYSA-N 3-(6-aminopyridine-3-carbonyl)-3,9-diazabicyclo[3.3.1]nonane-9-carboxylic acid Chemical compound C1=NC(N)=CC=C1C(=O)N1CC(N2C(O)=O)CCCC2C1 FQFWFNZKDPSDPX-UHFFFAOYSA-N 0.000 description 1
• CAIVQZLXOQRBME-UHFFFAOYSA-N 3-(6-nitropyridin-3-yl)-2-oxo-1-oxa-3,8-diazaspiro[4.5]decane-8-carboxylic acid Chemical compound C1CN(CCC12CN(C(=O)O2)C3=CN=C(C=C3)[N+](=O)[O-])C(=O)O CAIVQZLXOQRBME-UHFFFAOYSA-N 0.000 description 1
• UNFLLFITXYUAKZ-UHFFFAOYSA-N 3-[2-chloro-4-(cyclohexylamino)pyrimidin-5-yl]prop-2-yn-1-ol Chemical compound OCC#CC1=CN=C(Cl)N=C1NC1CCCCC1 UNFLLFITXYUAKZ-UHFFFAOYSA-N 0.000 description 1
• WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
• XPZYBFOYRKOKPL-UHFFFAOYSA-N 3-azabicyclo[3.2.1]octan-8-ol Chemical compound C1NCC2CCC1C2O XPZYBFOYRKOKPL-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• FYSCXTRDKBSUBL-UHFFFAOYSA-N 3-benzyl-3,9-diazabicyclo[3.3.1]nonane Chemical compound C1C(N2)CCCC2CN1CC1=CC=CC=C1 FYSCXTRDKBSUBL-UHFFFAOYSA-N 0.000 description 1
• IRGRGNINMVLGBC-UHFFFAOYSA-N 3-benzyl-8-methyl-3-azabicyclo[3.2.1]octan-8-ol Chemical compound CC1(O)C(C2)CCC1CN2CC1=CC=CC=C1 IRGRGNINMVLGBC-UHFFFAOYSA-N 0.000 description 1
• SPWTXMHCNCTDOK-UHFFFAOYSA-N 4-(6-aminopyridin-3-yl)-1,4-diazabicyclo[3.2.2]nonan-3-one Chemical compound C1=NC(N)=CC=C1N1C(=O)CN2CCC1CC2 SPWTXMHCNCTDOK-UHFFFAOYSA-N 0.000 description 1
• JWGUUGQGCXOEAR-UHFFFAOYSA-N 4-(6-nitropyridin-3-yl)-3-oxo-4,9-diazabicyclo[4.2.1]nonane-9-carboxylic acid Chemical compound OC(=O)N1C(C2)CCC1CC(=O)N2C1=CC=C([N+]([O-])=O)N=C1 JWGUUGQGCXOEAR-UHFFFAOYSA-N 0.000 description 1
• KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
• PHMYBXQQYPPIFY-UHFFFAOYSA-N 5-benzyl-8-methyl-3-azabicyclo[3.2.1]octan-8-ol Chemical compound CC1(O)C(CNC2)CCC12CC1=CC=CC=C1 PHMYBXQQYPPIFY-UHFFFAOYSA-N 0.000 description 1
• KHXNGFJREJNACT-UHFFFAOYSA-N 5-bromo-2-chloro-n-cycloheptylpyrimidin-4-amine Chemical compound ClC1=NC=C(Br)C(NC2CCCCCC2)=N1 KHXNGFJREJNACT-UHFFFAOYSA-N 0.000 description 1
• JYOUEBCJBKOBRG-UHFFFAOYSA-N 5-bromo-2-chloro-n-cyclohexylpyrimidin-4-amine Chemical compound ClC1=NC=C(Br)C(NC2CCCCC2)=N1 JYOUEBCJBKOBRG-UHFFFAOYSA-N 0.000 description 1
• HXFLZWAZSSPLCO-UHFFFAOYSA-N 6,6-dimethylbicyclo[3.1.1]heptyl Chemical group C1[C-]2C([CH2+])([CH2-])[C+]1CCC2 HXFLZWAZSSPLCO-UHFFFAOYSA-N 0.000 description 1
• KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
• UJQRJFOFOQZRMR-UHFFFAOYSA-N 7-cyclohexyl-2-[[6-(3,8-diazabicyclo[3.2.1]octan-3-yl)pyridazin-3-yl]amino]pyrrolo[2,3-d]pyrimidine-6-carboxylic acid Chemical compound C1(CCCCC1)N1C(=CC2=C1N=C(N=C2)NC=1N=NC(=CC=1)N1CC2CCC(C1)N2)C(=O)O UJQRJFOFOQZRMR-UHFFFAOYSA-N 0.000 description 1
• OEACICXLKCZAIY-UHFFFAOYSA-N 7-cyclopentyl-2-[[5-[8-(1-hydroxypropan-2-yl)-3,8-diazabicyclo[3.2.1]octane-3-carbonyl]pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound OCC(C)N1C(C2)CCC1CN2C(=O)C(C=N1)=CC=C1NC(N=C12)=NC=C1C=C(C(=O)N(C)C)N2C1CCCC1 OEACICXLKCZAIY-UHFFFAOYSA-N 0.000 description 1
• YFTHNXLMZZSIID-UHFFFAOYSA-N 7-cyclopentyl-2-[[5-[8-(2-hydroxyethyl)-3,8-diazabicyclo[3.2.1]octane-3-carbonyl]pyridin-2-yl]amino]-n,n-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC2=CN=C(NC=3N=CC(=CC=3)C(=O)N3CC4CCC(N4CCO)C3)N=C2N1C1CCCC1 YFTHNXLMZZSIID-UHFFFAOYSA-N 0.000 description 1
• HHZKYTGSMOMGOQ-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid Chemical compound N1=CN=C2NC(C(=O)O)=CC2=C1 HHZKYTGSMOMGOQ-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
• OFNWMZRPXFBZPX-UHFFFAOYSA-N 8-methyl-3,8-diazabicyclo[3.2.1]octane Chemical compound C1NCC2CCC1N2C OFNWMZRPXFBZPX-UHFFFAOYSA-N 0.000 description 1
• POOPWPIOIMBTOH-UHFFFAOYSA-N 8-oxa-3-azabicyclo[3.2.1]octane Chemical compound C1NCC2CCC1O2 POOPWPIOIMBTOH-UHFFFAOYSA-N 0.000 description 1
• 208000030507 AIDS Diseases 0.000 description 1
• 206010065040 AIDS dementia complex Diseases 0.000 description 1
• 241000251468 Actinopterygii Species 0.000 description 1
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
• 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
• 208000036762 Acute promyelocytic leukaemia Diseases 0.000 description 1
• 229920001817 Agar Polymers 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• 208000024827 Alzheimer disease Diseases 0.000 description 1
• 244000144725 Amygdalus communis Species 0.000 description 1
• 208000032467 Aplastic anaemia Diseases 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
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
• 208000003950 B-cell lymphoma Diseases 0.000 description 1
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
• 229940124130 Bcl inhibitor Drugs 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• OFCNTEIRIPNUDH-UHFFFAOYSA-N C(C1=CC=CC=C1)OC(=O)C1(CC=CC=C1)C(=O)C(O)C1=CC=CC=C1 Chemical compound C(C1=CC=CC=C1)OC(=O)C1(CC=CC=C1)C(=O)C(O)C1=CC=CC=C1 OFCNTEIRIPNUDH-UHFFFAOYSA-N 0.000 description 1
• KXGOPETVBIUYIZ-RDJZCZTQSA-N C1(CCCC1)N1C(=CC2=C1N=C(N=C2)NC1=NC=C(C=C1)C(=O)N1[C@@H]2CN[C@H](C1)C2)C(=O)O Chemical compound C1(CCCC1)N1C(=CC2=C1N=C(N=C2)NC1=NC=C(C=C1)C(=O)N1[C@@H]2CN[C@H](C1)C2)C(=O)O KXGOPETVBIUYIZ-RDJZCZTQSA-N 0.000 description 1
• JUXCGTRRLDBDRN-UHFFFAOYSA-N C1CC2CNCC(C1)N2C(=O)OCC3=CC=CC=C3 Chemical compound C1CC2CNCC(C1)N2C(=O)OCC3=CC=CC=C3 JUXCGTRRLDBDRN-UHFFFAOYSA-N 0.000 description 1
• HOXFFLXDZKUPRP-UHFFFAOYSA-N CC1C(OC(C(O1)([K])C)(C)C)(C)C Chemical compound CC1C(OC(C(O1)([K])C)(C)C)(C)C HOXFFLXDZKUPRP-UHFFFAOYSA-N 0.000 description 1
• BDAOHJMCJRVIKU-UHFFFAOYSA-N CC1C(OC(C(O1)([Li])C)(C)C)(C)C Chemical compound CC1C(OC(C(O1)([Li])C)(C)C)(C)C BDAOHJMCJRVIKU-UHFFFAOYSA-N 0.000 description 1
• 101150114156 CDK6 gene Proteins 0.000 description 1
• 229940125888 CDK7 inhibitor Drugs 0.000 description 1
• 108091007914 CDKs Proteins 0.000 description 1
• 206010058019 Cancer Pain Diseases 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
• 208000006029 Cardiomegaly Diseases 0.000 description 1
• 208000024172 Cardiovascular disease Diseases 0.000 description 1
• 241000282693 Cercopithecidae Species 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• 208000010833 Chronic myeloid leukaemia 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
• 206010048832 Colon adenoma Diseases 0.000 description 1
• 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 241000195493 Cryptophyta Species 0.000 description 1
• 108010024986 Cyclin-Dependent Kinase 2 Proteins 0.000 description 1
• 108010025454 Cyclin-Dependent Kinase 5 Proteins 0.000 description 1
• 102000000578 Cyclin-Dependent Kinase Inhibitor p21 Human genes 0.000 description 1
• 108010016788 Cyclin-Dependent Kinase Inhibitor p21 Proteins 0.000 description 1
• 102100036239 Cyclin-dependent kinase 2 Human genes 0.000 description 1
• 102100024456 Cyclin-dependent kinase 8 Human genes 0.000 description 1
• 102100024457 Cyclin-dependent kinase 9 Human genes 0.000 description 1
• 102000003903 Cyclin-dependent kinases Human genes 0.000 description 1
• 108090000266 Cyclin-dependent kinases Proteins 0.000 description 1
• 102100026805 Cyclin-dependent-like kinase 5 Human genes 0.000 description 1
• 229920000858 Cyclodextrin Polymers 0.000 description 1
• 201000003883 Cystic fibrosis Diseases 0.000 description 1
• 102000004127 Cytokines Human genes 0.000 description 1
• 108090000695 Cytokines Proteins 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
• AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
• KDXKERNSBIXSRK-RXMQYKEDSA-N D-lysine Chemical compound NCCCC[C@@H](N)C(O)=O KDXKERNSBIXSRK-RXMQYKEDSA-N 0.000 description 1
• 230000004544 DNA amplification Effects 0.000 description 1
• 206010073135 Dedifferentiated liposarcoma Diseases 0.000 description 1
• DBAKFASWICGISY-DASCVMRKSA-N Dexchlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C1([C@H](CCN(C)C)C=2N=CC=CC=2)=CC=C(Cl)C=C1 DBAKFASWICGISY-DASCVMRKSA-N 0.000 description 1
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
• 108010093502 E2F Transcription Factors Proteins 0.000 description 1
• 102000001388 E2F Transcription Factors Human genes 0.000 description 1
• 108050002772 E3 ubiquitin-protein ligase Mdm2 Proteins 0.000 description 1
• 238000008157 ELISA kit Methods 0.000 description 1
• XXPXYPLPSDPERN-UHFFFAOYSA-N Ecteinascidin 743 Natural products COc1cc2C(NCCc2cc1O)C(=O)OCC3N4C(O)C5Cc6cc(C)c(OC)c(O)c6C(C4C(S)c7c(OC(=O)C)c(C)c8OCOc8c37)N5C XXPXYPLPSDPERN-UHFFFAOYSA-N 0.000 description 1
• 206010014733 Endometrial cancer Diseases 0.000 description 1
• 206010014759 Endometrial neoplasm Diseases 0.000 description 1
• 108090000371 Esterases Proteins 0.000 description 1
• HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 201000008808 Fibrosarcoma Diseases 0.000 description 1
• KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
• 208000032612 Glial tumor Diseases 0.000 description 1
• 201000010915 Glioblastoma multiforme Diseases 0.000 description 1
• 206010018338 Glioma Diseases 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• 244000068988 Glycine max Species 0.000 description 1
• 235000010469 Glycine max Nutrition 0.000 description 1
• 208000017604 Hodgkin disease Diseases 0.000 description 1
• 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
• 101100495322 Homo sapiens CDK6 gene Proteins 0.000 description 1
• 101000715942 Homo sapiens Cyclin-dependent kinase 4 Proteins 0.000 description 1
• 101000980937 Homo sapiens Cyclin-dependent kinase 8 Proteins 0.000 description 1
• 101000980930 Homo sapiens Cyclin-dependent kinase 9 Proteins 0.000 description 1
• 101000980756 Homo sapiens G1/S-specific cyclin-D1 Proteins 0.000 description 1
• 101000736088 Homo sapiens PC4 and SFRS1-interacting protein Proteins 0.000 description 1
• 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 1
• 101000733249 Homo sapiens Tumor suppressor ARF Proteins 0.000 description 1
• 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
• 241000701044 Human gammaherpesvirus 4 Species 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
• 208000007766 Kaposi sarcoma Diseases 0.000 description 1
• 206010023347 Keratoacanthoma Diseases 0.000 description 1
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 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
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• 102100032913 Leukocyte surface antigen CD47 Human genes 0.000 description 1
• JXLYSJRDGCGARV-PJXZDTQASA-N Leurosidine 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-PJXZDTQASA-N 0.000 description 1
• LPGWZGMPDKDHEP-HLTPFJCJSA-N Leurosine Chemical compound C([C@]1([C@@H]2O1)CC)N(CCC=1C3=CC=CC=C3NC=11)C[C@H]2C[C@]1(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 LPGWZGMPDKDHEP-HLTPFJCJSA-N 0.000 description 1
• LPGWZGMPDKDHEP-GKWAKPNHSA-N Leurosine 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@]6(CC)O[C@@H]6[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C LPGWZGMPDKDHEP-GKWAKPNHSA-N 0.000 description 1
• YEJCDKJIEMIWRQ-UHFFFAOYSA-N Linopirdine Chemical compound O=C1N(C=2C=CC=CC=2)C2=CC=CC=C2C1(CC=1C=CN=CC=1)CC1=CC=NC=C1 YEJCDKJIEMIWRQ-UHFFFAOYSA-N 0.000 description 1
• 239000012448 Lithium borohydride Substances 0.000 description 1
• 208000031422 Lymphocytic Chronic B-Cell Leukemia 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
• 229940083338 MDM2 inhibitor Drugs 0.000 description 1
• 239000012819 MDM2-Inhibitor Substances 0.000 description 1
• 229940124647 MEK inhibitor Drugs 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 206010027476 Metastases Diseases 0.000 description 1
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
• HRHKSTOGXBBQCB-UHFFFAOYSA-N Mitomycin E Natural products O=C1C(N)=C(C)C(=O)C2=C1C(COC(N)=O)C1(OC)C3N(C)C3CN12 HRHKSTOGXBBQCB-UHFFFAOYSA-N 0.000 description 1
• 241000699666 Mus <mouse, genus> Species 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
• AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
• XUYPXLNMDZIRQH-LURJTMIESA-N N-acetyl-L-methionine Chemical compound CSCC[C@@H](C(O)=O)NC(C)=O XUYPXLNMDZIRQH-LURJTMIESA-N 0.000 description 1
• QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 1
• YPIGGYHFMKJNKV-UHFFFAOYSA-N N-ethylglycine Chemical compound CC[NH2+]CC([O-])=O YPIGGYHFMKJNKV-UHFFFAOYSA-N 0.000 description 1
• 108010065338 N-ethylglycine Proteins 0.000 description 1
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
• DGCDJRQCBBBZQU-UHFFFAOYSA-N NC1=CC=C(C=N1)N1C(C2(CCC1)CCN(CC2)C(=O)O)=O Chemical compound NC1=CC=C(C=N1)N1C(C2(CCC1)CCN(CC2)C(=O)O)=O DGCDJRQCBBBZQU-UHFFFAOYSA-N 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• 206010029260 Neuroblastoma Diseases 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 1
• 235000019502 Orange oil Nutrition 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• 102100036220 PC4 and SFRS1-interacting protein Human genes 0.000 description 1
• 239000012828 PI3K inhibitor Substances 0.000 description 1
• 102000038030 PI3Ks Human genes 0.000 description 1
• 108091007960 PI3Ks Proteins 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 108010011536 PTEN Phosphohydrolase Proteins 0.000 description 1
• 102000014160 PTEN Phosphohydrolase Human genes 0.000 description 1
• 208000018737 Parkinson disease Diseases 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• 229930182555 Penicillin Natural products 0.000 description 1
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
• NQRYJNQNLNOLGT-UHFFFAOYSA-O Piperidinium(1+) Chemical compound C1CC[NH2+]CC1 NQRYJNQNLNOLGT-UHFFFAOYSA-O 0.000 description 1
• 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 1
• 229920001213 Polysorbate 20 Polymers 0.000 description 1
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
• 102000001253 Protein Kinase Human genes 0.000 description 1
• 201000004681 Psoriasis Diseases 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
• 239000012980 RPMI-1640 medium Substances 0.000 description 1
• 206010063837 Reperfusion injury Diseases 0.000 description 1
• 208000007014 Retinitis pigmentosa Diseases 0.000 description 1
• 201000000582 Retinoblastoma Diseases 0.000 description 1
• 206010039491 Sarcoma Diseases 0.000 description 1
• 201000010208 Seminoma Diseases 0.000 description 1
• BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
• 241000580858 Simian-Human immunodeficiency virus Species 0.000 description 1
• 241000710960 Sindbis virus Species 0.000 description 1
• 208000000453 Skin Neoplasms Diseases 0.000 description 1
• 206010041067 Small cell lung cancer Diseases 0.000 description 1
• 108010090804 Streptavidin Proteins 0.000 description 1
• 208000006011 Stroke Diseases 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• 210000001744 T-lymphocyte Anatomy 0.000 description 1
• 206010043276 Teratoma Diseases 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• 239000013504 Triton X-100 Substances 0.000 description 1
• 229920004890 Triton X-100 Polymers 0.000 description 1
• 229940122618 Trypsin inhibitor Drugs 0.000 description 1
• 101710162629 Trypsin inhibitor Proteins 0.000 description 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
• 206010046851 Uveitis Diseases 0.000 description 1
• 240000001717 Vaccinium macrocarpon Species 0.000 description 1
• 235000012545 Vaccinium macrocarpon Nutrition 0.000 description 1
• 235000002118 Vaccinium oxycoccus Nutrition 0.000 description 1
• 208000036142 Viral infection Diseases 0.000 description 1
• 201000006083 Xeroderma Pigmentosum Diseases 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
• 238000002835 absorbance Methods 0.000 description 1
• 239000002250 absorbent Substances 0.000 description 1
• 230000002745 absorbent Effects 0.000 description 1
• JXLYSJRDGCGARV-KSNABSRWSA-N ac1l29ym 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-KSNABSRWSA-N 0.000 description 1
• 150000001242 acetic acid derivatives Chemical class 0.000 description 1
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
• CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 1
• LOPDCIIFIZYICH-UHFFFAOYSA-N acetonitrile;n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CC#N.CCN(C(C)C)C(C)C LOPDCIIFIZYICH-UHFFFAOYSA-N 0.000 description 1
• 229960001138 acetylsalicylic acid Drugs 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• YBCVMFKXIKNREZ-UHFFFAOYSA-N acoh acetic acid Chemical compound CC(O)=O.CC(O)=O YBCVMFKXIKNREZ-UHFFFAOYSA-N 0.000 description 1
• 239000012190 activator Substances 0.000 description 1
• 230000001154 acute effect Effects 0.000 description 1
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
• 239000003463 adsorbent Substances 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 235000010419 agar Nutrition 0.000 description 1
• 206010064930 age-related macular degeneration Diseases 0.000 description 1
• 239000000556 agonist Substances 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• 150000001299 aldehydes Chemical class 0.000 description 1
• 150000001335 aliphatic alkanes Chemical class 0.000 description 1
• 125000003342 alkenyl group Chemical group 0.000 description 1
• 229920000180 alkyd Polymers 0.000 description 1
• 125000005055 alkyl alkoxy group Chemical group 0.000 description 1
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 1
• 235000020224 almond Nutrition 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 235000012211 aluminium silicate Nutrition 0.000 description 1
• SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 description 1
• 229960000836 amitriptyline Drugs 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• 208000007502 anemia Diseases 0.000 description 1
• 239000000051 antiandrogen Substances 0.000 description 1
• 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 230000006907 apoptotic process Effects 0.000 description 1
• 239000012736 aqueous medium Substances 0.000 description 1
• 239000007900 aqueous suspension Substances 0.000 description 1
• 230000006793 arrhythmia Effects 0.000 description 1
• 206010003119 arrhythmia Diseases 0.000 description 1
• 210000001367 artery Anatomy 0.000 description 1
• 206010003246 arthritis Diseases 0.000 description 1
• 125000001769 aryl amino group Chemical group 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-L aspartate group Chemical class N[C@@H](CC(=O)[O-])C(=O)[O-] CKLJMWTZIZZHCS-REOHCLBHSA-L 0.000 description 1
• 239000012131 assay buffer Substances 0.000 description 1
• 230000001363 autoimmune Effects 0.000 description 1
• YCNIBOIOWCTRCL-UHFFFAOYSA-N azane;2,2,2-trifluoroacetic acid Chemical compound [NH4+].[O-]C(=O)C(F)(F)F YCNIBOIOWCTRCL-UHFFFAOYSA-N 0.000 description 1
• 230000004888 barrier function Effects 0.000 description 1
• 150000007514 bases Chemical class 0.000 description 1
• JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
• HSEVGTNHODLPRX-UHFFFAOYSA-N benzoic acid;2,3-dihydroxybutanedioic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C(O)C(O)C(O)=O HSEVGTNHODLPRX-UHFFFAOYSA-N 0.000 description 1
• SPVCUIHUEABWQP-HUUCEWRRSA-N benzyl (3ar,8as)-3,3a,4,5,6,7,8,8a-octahydro-2h-pyrrolo[2,3-c]azepine-1-carboxylate Chemical compound N1([C@@H]2CNCCC[C@@H]2CC1)C(=O)OCC1=CC=CC=C1 SPVCUIHUEABWQP-HUUCEWRRSA-N 0.000 description 1
• KFKJACLLRKRWJE-UHFFFAOYSA-N benzyl 3,8-diazabicyclo[3.2.1]octane-3-carboxylate Chemical compound C1C(N2)CCC2CN1C(=O)OCC1=CC=CC=C1 KFKJACLLRKRWJE-UHFFFAOYSA-N 0.000 description 1
• BSNVJGVVANNMNX-UHFFFAOYSA-N benzyl 3-oxa-7,9-diazabicyclo[3.3.1]nonane-9-carboxylate Chemical compound C1OCC2CNCC1N2C(=O)OCC1=CC=CC=C1 BSNVJGVVANNMNX-UHFFFAOYSA-N 0.000 description 1
• HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-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
• LPCWKMYWISGVSK-UHFFFAOYSA-N bicyclo[3.2.1]octane Chemical compound C1C2CCC1CCC2 LPCWKMYWISGVSK-UHFFFAOYSA-N 0.000 description 1
• 239000012148 binding buffer Substances 0.000 description 1
• 239000012620 biological material Substances 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 229960002685 biotin Drugs 0.000 description 1
• 235000020958 biotin Nutrition 0.000 description 1
• 239000011616 biotin Substances 0.000 description 1
• 230000000903 blocking effect Effects 0.000 description 1
• 210000001185 bone marrow Anatomy 0.000 description 1
• GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• 229940045348 brown mixture Drugs 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
• 229910000024 caesium carbonate Inorganic materials 0.000 description 1
• 235000010216 calcium carbonate Nutrition 0.000 description 1
• FATUQANACHZLRT-KMRXSBRUSA-L calcium glucoheptonate Chemical compound [Ca+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O FATUQANACHZLRT-KMRXSBRUSA-L 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• 238000004364 calculation method Methods 0.000 description 1
• MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
• 239000004202 carbamide Substances 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 125000002843 carboxylic acid group Chemical group 0.000 description 1
• 150000001735 carboxylic acids Chemical class 0.000 description 1
• XREUEWVEMYWFFA-CSKJXFQVSA-N carminomycin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=C(O)C=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XREUEWVEMYWFFA-CSKJXFQVSA-N 0.000 description 1
• 229930188550 carminomycin Natural products 0.000 description 1
• XREUEWVEMYWFFA-UHFFFAOYSA-N carminomycin I Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=C(O)C=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XREUEWVEMYWFFA-UHFFFAOYSA-N 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 229950001725 carubicin Drugs 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 238000000423 cell based assay Methods 0.000 description 1
• 230000006369 cell cycle progression Effects 0.000 description 1
• 230000024245 cell differentiation Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• 208000025434 cerebellar degeneration Diseases 0.000 description 1
• 210000003679 cervix uteri Anatomy 0.000 description 1
• 230000009920 chelation Effects 0.000 description 1
• 239000007795 chemical reaction product Substances 0.000 description 1
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
• 229910052801 chlorine Inorganic materials 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• QOPVNWQGBQYBBP-UHFFFAOYSA-N chloroethyl chloroformate Chemical compound CC(Cl)OC(Cl)=O QOPVNWQGBQYBBP-UHFFFAOYSA-N 0.000 description 1
• 208000037976 chronic inflammation Diseases 0.000 description 1
• 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
• 238000011278 co-treatment Methods 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 210000001072 colon Anatomy 0.000 description 1
• 201000010897 colon adenocarcinoma Diseases 0.000 description 1
• 239000013066 combination product Substances 0.000 description 1
• 229940127555 combination product Drugs 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 239000002537 cosmetic Substances 0.000 description 1
• 235000004634 cranberry Nutrition 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
• 229940043378 cyclin-dependent kinase inhibitor Drugs 0.000 description 1
• 229940097362 cyclodextrins Drugs 0.000 description 1
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
• 231100000433 cytotoxic Toxicity 0.000 description 1
• 230000001472 cytotoxic effect Effects 0.000 description 1
• 238000007405 data analysis Methods 0.000 description 1
• DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• ICMYIQTVBRLNEE-UHFFFAOYSA-N decyl(dimethyl)azanium;chloride Chemical compound Cl.CCCCCCCCCCN(C)C ICMYIQTVBRLNEE-UHFFFAOYSA-N 0.000 description 1
• 230000007547 defect Effects 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 230000018109 developmental process Effects 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 125000006003 dichloroethyl group Chemical group 0.000 description 1
• YMWUJEATGCHHMB-DICFDUPASA-N dichloromethane-d2 Chemical compound [2H]C([2H])(Cl)Cl YMWUJEATGCHHMB-DICFDUPASA-N 0.000 description 1
• IIJREXIVDSIOFR-UHFFFAOYSA-N dichloromethane;heptane Chemical compound ClCCl.CCCCCCC IIJREXIVDSIOFR-UHFFFAOYSA-N 0.000 description 1
• BLEBFDYUDVZRFG-UHFFFAOYSA-N dichloromethane;propan-2-ol Chemical compound ClCCl.CC(C)O BLEBFDYUDVZRFG-UHFFFAOYSA-N 0.000 description 1
• 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
• WSFSSNUMVMOOMR-DICFDUPASA-N dideuteriomethanone Chemical compound [2H]C([2H])=O WSFSSNUMVMOOMR-DICFDUPASA-N 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 1
• 125000006001 difluoroethyl group Chemical group 0.000 description 1
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 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
• 150000002013 dioxins Chemical class 0.000 description 1
• SXZIXHOMFPUIRK-UHFFFAOYSA-N diphenylmethanimine Chemical compound C=1C=CC=CC=1C(=N)C1=CC=CC=C1 SXZIXHOMFPUIRK-UHFFFAOYSA-N 0.000 description 1
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
• 229940043264 dodecyl sulfate Drugs 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 229960004679 doxorubicin Drugs 0.000 description 1
• 229940112141 dry powder inhaler Drugs 0.000 description 1
• 229940121647 egfr inhibitor Drugs 0.000 description 1
• 238000003821 enantio-separation Methods 0.000 description 1
• 230000002357 endometrial effect Effects 0.000 description 1
• 239000003623 enhancer Substances 0.000 description 1
• 238000007824 enzymatic assay Methods 0.000 description 1
• 210000002615 epidermis Anatomy 0.000 description 1
• 208000037828 epithelial carcinoma Diseases 0.000 description 1
• 229960003276 erythromycin Drugs 0.000 description 1
• 238000005886 esterification reaction Methods 0.000 description 1
• AFAXGSQYZLGZPG-UHFFFAOYSA-L ethane-1,2-disulfonate Chemical compound [O-]S(=O)(=O)CCS([O-])(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-L 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 1
• 150000002170 ethers Chemical class 0.000 description 1
• 239000002024 ethyl acetate extract Substances 0.000 description 1
• RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
• 229960005167 everolimus Drugs 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 201000000497 familial melanoma Diseases 0.000 description 1
• 229940125829 fibroblast growth factor receptor inhibitor Drugs 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 235000011087 fumaric acid Nutrition 0.000 description 1
• 210000000232 gallbladder Anatomy 0.000 description 1
• 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 230000009395 genetic defect Effects 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 210000004907 gland Anatomy 0.000 description 1
• 239000011521 glass Substances 0.000 description 1
• 208000005017 glioblastoma Diseases 0.000 description 1
• 239000003862 glucocorticoid Substances 0.000 description 1
• 229940050410 gluconate Drugs 0.000 description 1
• 229940097042 glucuronate Drugs 0.000 description 1
• 229960002989 glutamic acid Drugs 0.000 description 1
• 229940074045 glyceryl distearate Drugs 0.000 description 1
• 229940075507 glyceryl monostearate Drugs 0.000 description 1
• 239000003102 growth factor Substances 0.000 description 1
• 239000001963 growth medium Substances 0.000 description 1
• 239000007902 hard capsule Substances 0.000 description 1
• 230000012447 hatching Effects 0.000 description 1
• 210000003128 head Anatomy 0.000 description 1
• 239000003481 heat shock protein 90 inhibitor Substances 0.000 description 1
• 208000014951 hematologic disease Diseases 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
• GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
• 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 1
• 108091008039 hormone receptors Proteins 0.000 description 1
• 102000048992 human CDK4 Human genes 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
• BDAGIHXWWSANSR-NJFSPNSNSA-N hydroxyformaldehyde Chemical compound O[14CH]=O BDAGIHXWWSANSR-NJFSPNSNSA-N 0.000 description 1
• 230000003463 hyperproliferative effect Effects 0.000 description 1
• 238000003384 imaging method Methods 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 230000001900 immune effect Effects 0.000 description 1
• 229960003444 immunosuppressant agent Drugs 0.000 description 1
• 230000001861 immunosuppressant effect Effects 0.000 description 1
• 229940125721 immunosuppressive agent Drugs 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 239000007972 injectable composition Substances 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• 239000003456 ion exchange resin Substances 0.000 description 1
• 229920003303 ion-exchange polymer Polymers 0.000 description 1
• 229910052742 iron Inorganic materials 0.000 description 1
• JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical group C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 description 1
• 208000037906 ischaemic injury Diseases 0.000 description 1
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound 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
• 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
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
• 230000000155 isotopic effect Effects 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
• 150000002576 ketones Chemical class 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 208000017169 kidney disease Diseases 0.000 description 1
• 238000012933 kinetic analysis Methods 0.000 description 1
• 229940001447 lactate Drugs 0.000 description 1
• 229940099584 lactobionate Drugs 0.000 description 1
• JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
• 208000032839 leukemia Diseases 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 238000004811 liquid chromatography Methods 0.000 description 1
• 229940057995 liquid paraffin Drugs 0.000 description 1
• YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 208000019423 liver disease Diseases 0.000 description 1
• 230000004807 localization Effects 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 231100000053 low toxicity Toxicity 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 210000002751 lymph Anatomy 0.000 description 1
• 239000006166 lysate Substances 0.000 description 1
• 229960003646 lysine Drugs 0.000 description 1
• 239000012139 lysis buffer Substances 0.000 description 1
• 208000002780 macular degeneration Diseases 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
• 229940049920 malate Drugs 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 210000004962 mammalian cell Anatomy 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
• 229960002510 mandelic acid Drugs 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• BCVXHSPFUWZLGQ-UHFFFAOYSA-N mecn acetonitrile Chemical compound CC#N.CC#N BCVXHSPFUWZLGQ-UHFFFAOYSA-N 0.000 description 1
• 229960003194 meglumine Drugs 0.000 description 1
• SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
• 229960001924 melphalan Drugs 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 210000004379 membrane Anatomy 0.000 description 1
• COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• 230000009401 metastasis Effects 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
• WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
• QSRRZKPKHJHIRB-UHFFFAOYSA-N methyl 4-[(2,5-dichloro-4-methylthiophen-3-yl)sulfonylamino]-2-hydroxybenzoate Chemical compound C1=C(O)C(C(=O)OC)=CC=C1NS(=O)(=O)C1=C(Cl)SC(Cl)=C1C QSRRZKPKHJHIRB-UHFFFAOYSA-N 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• HRHKSTOGXBBQCB-VFWICMBZSA-N methylmitomycin Chemical compound O=C1C(N)=C(C)C(=O)C2=C1[C@@H](COC(N)=O)[C@@]1(OC)[C@H]3N(C)[C@H]3CN12 HRHKSTOGXBBQCB-VFWICMBZSA-N 0.000 description 1
• 239000003226 mitogen Substances 0.000 description 1
• 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 description 1
• 230000002297 mitogenic effect Effects 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 239000002808 molecular sieve Substances 0.000 description 1
• 239000004570 mortar (masonry) Substances 0.000 description 1
• 201000006417 multiple sclerosis Diseases 0.000 description 1
• 210000002346 musculoskeletal system Anatomy 0.000 description 1
• 208000010125 myocardial infarction Diseases 0.000 description 1
• PEECTLLHENGOKU-UHFFFAOYSA-N n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC=C1.CN(C)C1=CC=NC=C1 PEECTLLHENGOKU-UHFFFAOYSA-N 0.000 description 1
• IFYDWYVPVAMGRO-UHFFFAOYSA-N n-[3-(dimethylamino)propyl]tetradecanamide Chemical compound CCCCCCCCCCCCCC(=O)NCCCN(C)C IFYDWYVPVAMGRO-UHFFFAOYSA-N 0.000 description 1
• OBJNFLYHUXWUPF-IZZDOVSWSA-N n-[3-[[5-chloro-4-(1h-indol-3-yl)pyrimidin-2-yl]amino]phenyl]-4-[[(e)-4-(dimethylamino)but-2-enoyl]amino]benzamide Chemical compound C1=CC(NC(=O)/C=C/CN(C)C)=CC=C1C(=O)NC1=CC=CC(NC=2N=C(C(Cl)=CN=2)C=2C3=CC=CC=C3NC=2)=C1 OBJNFLYHUXWUPF-IZZDOVSWSA-N 0.000 description 1
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-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
• WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
• RIVIDPPYRINTTH-UHFFFAOYSA-N n-ethylpropan-2-amine Chemical compound CCNC(C)C RIVIDPPYRINTTH-UHFFFAOYSA-N 0.000 description 1
• IKVDMBQGHZVMRN-UHFFFAOYSA-N n-methyldecan-1-amine Chemical compound CCCCCCCCCCNC IKVDMBQGHZVMRN-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
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• PSZYNBSKGUBXEH-UHFFFAOYSA-M naphthalene-1-sulfonate Chemical compound C1=CC=C2C(S(=O)(=O)[O-])=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-M 0.000 description 1
• 210000003739 neck Anatomy 0.000 description 1
• 208000007538 neurilemmoma Diseases 0.000 description 1
• 208000015122 neurodegenerative disease Diseases 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• 150000002823 nitrates Chemical class 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
• 210000001331 nose Anatomy 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-M octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC([O-])=O QIQXTHQIDYTFRH-UHFFFAOYSA-M 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-M oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC([O-])=O ZQPPMHVWECSIRJ-KTKRTIGZSA-M 0.000 description 1
• 229940049964 oleate Drugs 0.000 description 1
• 239000004006 olive oil Substances 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 231100000590 oncogenic Toxicity 0.000 description 1
• 230000002246 oncogenic effect Effects 0.000 description 1
• 239000010502 orange oil Substances 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 201000008968 osteosarcoma Diseases 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 239000006174 pH buffer Substances 0.000 description 1
• 238000004806 packaging method and process Methods 0.000 description 1
• 229910052763 palladium Inorganic materials 0.000 description 1
• LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
• 210000000496 pancreas Anatomy 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 239000006072 paste Substances 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• 235000019371 penicillin G benzathine Nutrition 0.000 description 1
• 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
• 230000000737 periodic effect Effects 0.000 description 1
• 210000001428 peripheral nervous system Anatomy 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 150000002989 phenols Chemical class 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 description 1
• 150000003904 phospholipids Chemical class 0.000 description 1
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• 239000011574 phosphorus Substances 0.000 description 1
• IEQIEDJGQAUEQZ-UHFFFAOYSA-N phthalocyanine Chemical compound N1C(N=C2C3=CC=CC=C3C(N=C3C4=CC=CC=C4C(=N4)N3)=N2)=C(C=CC=C2)C2=C1N=C1C2=CC=CC=C2C4=N1 IEQIEDJGQAUEQZ-UHFFFAOYSA-N 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 229960005141 piperazine Drugs 0.000 description 1
• 239000004033 plastic Substances 0.000 description 1
• 229920003023 plastic Polymers 0.000 description 1
• 230000010287 polarization Effects 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
• 229920002223 polystyrene Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 229950004406 porfiromycin Drugs 0.000 description 1
• IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
• 230000035935 pregnancy Effects 0.000 description 1
• 238000002953 preparative HPLC Methods 0.000 description 1
• 230000036278 prepulse Effects 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• 230000000750 progressive effect Effects 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 239000003380 propellant Substances 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
• 210000002307 prostate Anatomy 0.000 description 1
• 108060006633 protein kinase Proteins 0.000 description 1
• 239000003909 protein kinase inhibitor Substances 0.000 description 1
• 230000001696 purinergic effect Effects 0.000 description 1
• 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
• OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 description 1
• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
• 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• 150000004060 quinone imines Chemical group 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• 239000000376 reactant Substances 0.000 description 1
• 230000008707 rearrangement Effects 0.000 description 1
• 238000006268 reductive amination reaction Methods 0.000 description 1
• 239000013643 reference control Substances 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 102000037983 regulatory factors Human genes 0.000 description 1
• 108091008025 regulatory factors Proteins 0.000 description 1
• 230000002336 repolarization Effects 0.000 description 1
• 208000037803 restenosis Diseases 0.000 description 1
• 230000036390 resting membrane potential Effects 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 201000009410 rhabdomyosarcoma Diseases 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 238000007363 ring formation reaction Methods 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• 238000007789 sealing Methods 0.000 description 1
• 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• 230000001953 sensory effect Effects 0.000 description 1
• 230000011664 signaling Effects 0.000 description 1
• 239000000377 silicon dioxide Substances 0.000 description 1
• 235000012239 silicon dioxide Nutrition 0.000 description 1
• 229910052709 silver Inorganic materials 0.000 description 1
• 239000004332 silver Substances 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
• 201000009890 sinusitis Diseases 0.000 description 1
• 201000000849 skin cancer Diseases 0.000 description 1
• 239000002002 slurry Substances 0.000 description 1
• 208000000587 small cell lung carcinoma Diseases 0.000 description 1
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
• 235000017557 sodium bicarbonate Nutrition 0.000 description 1
• WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical class [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 239000001488 sodium phosphate Substances 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
• 239000007901 soft capsule Substances 0.000 description 1
• 239000002689 soil Substances 0.000 description 1
• 238000000527 sonication Methods 0.000 description 1
• 239000004071 soot Substances 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 208000002320 spinal muscular atrophy Diseases 0.000 description 1
• 238000005507 spraying Methods 0.000 description 1
• 206010041823 squamous cell carcinoma Diseases 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 230000001954 sterilising effect Effects 0.000 description 1
• 238000004659 sterilization and disinfection Methods 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 239000011550 stock solution Substances 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 239000012089 stop solution Substances 0.000 description 1
• 229910000018 strontium carbonate Inorganic materials 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
• 239000005720 sucrose Substances 0.000 description 1
• 229910052717 sulfur Inorganic materials 0.000 description 1
• 230000000475 sunscreen effect Effects 0.000 description 1
• 239000000516 sunscreening agent Substances 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 230000001629 suppression Effects 0.000 description 1
• 238000001356 surgical procedure Methods 0.000 description 1
• 230000002194 synthesizing effect Effects 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
• UXAWXZDXVOYLII-HTQZYQBOSA-N tert-butyl (1r,4r)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C1[C@H]2N(C(=O)OC(C)(C)C)C[C@@H]1NC2 UXAWXZDXVOYLII-HTQZYQBOSA-N 0.000 description 1
• UXAWXZDXVOYLII-YUMQZZPRSA-N tert-butyl (1s,4s)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C1[C@@H]2N(C(=O)OC(C)(C)C)C[C@H]1NC2 UXAWXZDXVOYLII-YUMQZZPRSA-N 0.000 description 1
• IXKNPSLHUPHNQK-RYUDHWBXSA-N tert-butyl (1s,4s)-5-(6-aminopyridine-3-carbonyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C([C@]1(N(C[C@]2([H])C1)C(=O)OC(C)(C)C)[H])N2C(=O)C1=CC=C(N)N=C1 IXKNPSLHUPHNQK-RYUDHWBXSA-N 0.000 description 1
• SYYVJJWPPNEPGD-DTORHVGOSA-N tert-butyl (1s,5r)-3-oxa-7,9-diazabicyclo[3.3.1]nonane-7-carboxylate Chemical compound C1OC[C@]2([H])CN(C(=O)OC(C)(C)C)C[C@@]1([H])N2 SYYVJJWPPNEPGD-DTORHVGOSA-N 0.000 description 1
• KVOUHLVOTMOJBS-UHFFFAOYSA-N tert-butyl 2,6-diazaspiro[3.3]heptane-2-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC11CNC1 KVOUHLVOTMOJBS-UHFFFAOYSA-N 0.000 description 1
• GAFIPFHPWOEZCF-UHFFFAOYSA-N tert-butyl 2-(6-aminopyridin-3-yl)-1-oxo-2,9-diazaspiro[5.5]undecane-9-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC11C(=O)N(C=2C=NC(N)=CC=2)CCC1 GAFIPFHPWOEZCF-UHFFFAOYSA-N 0.000 description 1
• QOQHXJPJXOPAQH-UHFFFAOYSA-N tert-butyl 2-(6-nitropyridin-3-yl)-1-oxo-2,9-diazaspiro[5.5]undecane-9-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC11C(=O)N(C=2C=NC(=CC=2)[N+]([O-])=O)CCC1 QOQHXJPJXOPAQH-UHFFFAOYSA-N 0.000 description 1
• WEEMVXIMHUFIHA-UHFFFAOYSA-N tert-butyl 2-(6-nitropyridin-3-yl)-3-oxo-2,8-diazaspiro[4.5]decane-8-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC11CC(=O)N(C=2C=NC(=CC=2)[N+]([O-])=O)C1 WEEMVXIMHUFIHA-UHFFFAOYSA-N 0.000 description 1
• CSQBUSQTOWHXLW-UHFFFAOYSA-N tert-butyl 3,6-diazabicyclo[3.2.1]octane-6-carboxylate Chemical compound C1C2N(C(=O)OC(C)(C)C)CC1CNC2 CSQBUSQTOWHXLW-UHFFFAOYSA-N 0.000 description 1
• FQCAMCMQMJHPOU-UHFFFAOYSA-N tert-butyl 3-(6-aminopyridazin-3-yl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(C2)CCC1CN2C1=CC=C(N)N=N1 FQCAMCMQMJHPOU-UHFFFAOYSA-N 0.000 description 1
• ADCPOMUTWQVQMI-UHFFFAOYSA-N tert-butyl 3-(6-aminopyridin-3-yl)-4-oxo-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(C2)CCC1C(=O)N2C1=CC=C(N)N=C1 ADCPOMUTWQVQMI-UHFFFAOYSA-N 0.000 description 1
• STLNOUNQPWIHDG-UHFFFAOYSA-N tert-butyl 3-[(6-aminopyridin-3-yl)methyl]-3,8-diazabicyclo[3.2.1]octane-8-carboxylate Chemical compound CC(C)(C)OC(=O)N1C2CCC1CN(Cc1ccc(N)nc1)C2 STLNOUNQPWIHDG-UHFFFAOYSA-N 0.000 description 1
• MASXHWHKDFQBHX-UHFFFAOYSA-N tert-butyl 3-benzyl-3,9-diazabicyclo[3.3.1]nonane-9-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(C2)CCCC1CN2CC1=CC=CC=C1 MASXHWHKDFQBHX-UHFFFAOYSA-N 0.000 description 1
• IDJDDPDWYRVJPF-UHFFFAOYSA-N tert-butyl 4,9-diazabicyclo[4.2.1]nonane-9-carboxylate Chemical compound C1CNCC2CCC1N2C(=O)OC(C)(C)C IDJDDPDWYRVJPF-UHFFFAOYSA-N 0.000 description 1
• NTQVRXBWTSJKQT-UHFFFAOYSA-N tert-butyl 4-(6-nitropyridin-3-yl)-3-oxo-8-oxa-4,10-diazabicyclo[4.3.1]decane-10-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(C2)COCC1CC(=O)N2C1=CC=C([N+]([O-])=O)N=C1 NTQVRXBWTSJKQT-UHFFFAOYSA-N 0.000 description 1
• BBCMXUSDDGEGQP-UHFFFAOYSA-N tert-butyl 5-benzyl-3,9-diazabicyclo[3.3.1]nonane-9-carboxylate Chemical compound CC(C)(C)OC(=O)N1C(CNC2)CCCC12CC1=CC=CC=C1 BBCMXUSDDGEGQP-UHFFFAOYSA-N 0.000 description 1
• VCOYCEBPHSEGPA-UHFFFAOYSA-N tert-butyl 7-oxo-3,9-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1C(=O)CC2CN(C(=O)OC(C)(C)C)CC1N2 VCOYCEBPHSEGPA-UHFFFAOYSA-N 0.000 description 1
• LHJSYLNUEZBFED-UHFFFAOYSA-N tert-butyl 9-oxa-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate Chemical compound C1NCC2CN(C(=O)OC(C)(C)C)CC1O2 LHJSYLNUEZBFED-UHFFFAOYSA-N 0.000 description 1
• QIYOMZXJQAKHEK-DHBOJHSNSA-N tert-butyl n-[(1r,5s)-3-azabicyclo[3.1.0]hexan-6-yl]carbamate Chemical compound C1NC[C@H]2C(NC(=O)OC(C)(C)C)[C@H]21 QIYOMZXJQAKHEK-DHBOJHSNSA-N 0.000 description 1
• 125000006337 tetrafluoro ethyl group Chemical group 0.000 description 1
• WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
• 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 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
• 229960000278 theophylline Drugs 0.000 description 1
• 231100001274 therapeutic index Toxicity 0.000 description 1
• 150000003573 thiols Chemical class 0.000 description 1
• 210000001685 thyroid gland Anatomy 0.000 description 1
• 238000002877 time resolved fluorescence resonance energy transfer Methods 0.000 description 1
• 238000004448 titration Methods 0.000 description 1
• 238000000954 titration curve Methods 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
• 125000005425 toluyl group Chemical group 0.000 description 1
• 238000003325 tomography Methods 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 239000003053 toxin Substances 0.000 description 1
• 231100000765 toxin Toxicity 0.000 description 1
• 108700012359 toxins Proteins 0.000 description 1
• PKVRCIRHQMSYJX-AIFWHQITSA-N trabectedin Chemical compound C([C@@]1(C(OC2)=O)NCCC3=C1C=C(C(=C3)O)OC)S[C@@H]1C3=C(OC(C)=O)C(C)=C4OCOC4=C3[C@H]2N2[C@@H](O)[C@H](CC=3C4=C(O)C(OC)=C(C)C=3)N(C)[C@H]4[C@@H]21 PKVRCIRHQMSYJX-AIFWHQITSA-N 0.000 description 1
• 229960000977 trabectedin Drugs 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• 238000013518 transcription Methods 0.000 description 1
• 230000035897 transcription Effects 0.000 description 1
• 230000037317 transdermal delivery Effects 0.000 description 1
• 125000006000 trichloroethyl group Chemical group 0.000 description 1
• 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
• ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
• 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
• 229960000281 trometamol Drugs 0.000 description 1
• 239000002753 trypsin inhibitor Substances 0.000 description 1
• 241000701161 unidentified adenovirus Species 0.000 description 1
• 241000701447 unidentified baculovirus Species 0.000 description 1
• 241001529453 unidentified herpesvirus Species 0.000 description 1
• 238000011144 upstream manufacturing Methods 0.000 description 1
• 210000003932 urinary bladder Anatomy 0.000 description 1
• 229940099039 velcade Drugs 0.000 description 1
• 239000010455 vermiculite Substances 0.000 description 1
• 235000019354 vermiculite Nutrition 0.000 description 1
• 229910052902 vermiculite Inorganic materials 0.000 description 1
• 230000035899 viability Effects 0.000 description 1
• 230000009385 viral infection Effects 0.000 description 1
• 238000010792 warming Methods 0.000 description 1
• 238000001238 wet grinding Methods 0.000 description 1
• 238000009736 wetting Methods 0.000 description 1
• 208000016153 withdrawal disease Diseases 0.000 description 1
• UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1