WO2003011836A1 - Tyrosine kinase inhibitors - Google Patents
Tyrosine kinase inhibitors Download PDFInfo
- Publication number
- WO2003011836A1 WO2003011836A1 PCT/US2002/023764 US0223764W WO03011836A1 WO 2003011836 A1 WO2003011836 A1 WO 2003011836A1 US 0223764 W US0223764 W US 0223764W WO 03011836 A1 WO03011836 A1 WO 03011836A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- phenyl
- imidazol
- pyrimidin
- unsubstituted
- amine
- Prior art date
Links
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 title claims description 7
- 239000005483 tyrosine kinase inhibitor Substances 0.000 title claims description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 184
- 238000000034 method Methods 0.000 claims abstract description 94
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 54
- 239000000203 mixture Substances 0.000 claims abstract description 47
- 201000011510 cancer Diseases 0.000 claims abstract description 33
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims abstract description 32
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims abstract description 32
- 241000124008 Mammalia Species 0.000 claims abstract description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 17
- 230000033115 angiogenesis Effects 0.000 claims abstract description 16
- 201000010099 disease Diseases 0.000 claims abstract description 16
- 206010012689 Diabetic retinopathy Diseases 0.000 claims abstract description 10
- 230000001419 dependent effect Effects 0.000 claims abstract description 10
- 206010064930 age-related macular degeneration Diseases 0.000 claims abstract description 7
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 7
- 208000002780 macular degeneration Diseases 0.000 claims abstract description 7
- -1 3,5-Dimethylphenyl Chemical group 0.000 claims description 49
- 125000000623 heterocyclic group Chemical group 0.000 claims description 44
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims description 41
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims description 39
- 125000000217 alkyl group Chemical group 0.000 claims description 38
- 150000003839 salts Chemical class 0.000 claims description 33
- 239000003112 inhibitor Substances 0.000 claims description 32
- 125000003118 aryl group Chemical group 0.000 claims description 25
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 claims description 24
- 125000003107 substituted aryl group Chemical group 0.000 claims description 24
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 17
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 17
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 17
- 125000005843 halogen group Chemical group 0.000 claims description 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
- 239000004037 angiogenesis inhibitor Substances 0.000 claims description 12
- 229940121369 angiogenesis inhibitor Drugs 0.000 claims description 12
- 239000003102 growth factor Substances 0.000 claims description 12
- 230000002401 inhibitory effect Effects 0.000 claims description 12
- 108010044426 integrins Proteins 0.000 claims description 12
- 102000006495 integrins Human genes 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- 239000002834 estrogen receptor modulator Substances 0.000 claims description 10
- 125000005842 heteroatom Chemical group 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 9
- 229940127089 cytotoxic agent Drugs 0.000 claims description 9
- 239000002254 cytotoxic agent Substances 0.000 claims description 9
- 231100000599 cytotoxic agent Toxicity 0.000 claims description 9
- 239000003558 transferase inhibitor Substances 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 8
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 8
- 230000001028 anti-proliverative effect Effects 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 102000027483 retinoid hormone receptors Human genes 0.000 claims description 8
- 108091008679 retinoid hormone receptors Proteins 0.000 claims description 8
- 239000000849 selective androgen receptor modulator Substances 0.000 claims description 8
- VEEGZPWAAPPXRB-BJMVGYQFSA-N (3e)-3-(1h-imidazol-5-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=CC=C2\C1=C/C1=CN=CN1 VEEGZPWAAPPXRB-BJMVGYQFSA-N 0.000 claims description 7
- 229940123468 Transferase inhibitor Drugs 0.000 claims description 7
- 239000005557 antagonist Substances 0.000 claims description 7
- 125000001072 heteroaryl group Chemical group 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 claims description 7
- 201000004681 Psoriasis Diseases 0.000 claims description 6
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 claims description 6
- PVNVVSOCNKJUKM-UHFFFAOYSA-N [3-methyl-5-[[4-(2-phenylimidazol-1-yl)pyrimidin-2-yl]amino]phenyl]methanol Chemical compound CC1=CC(CO)=CC(NC=2N=C(C=CN=2)N2C(=NC=C2)C=2C=CC=CC=2)=C1 PVNVVSOCNKJUKM-UHFFFAOYSA-N 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000000369 oxido group Chemical group [*]=O 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 201000011461 pre-eclampsia Diseases 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 230000000451 tissue damage Effects 0.000 claims description 6
- 231100000827 tissue damage Toxicity 0.000 claims description 6
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 5
- XTKPPFQBRFSEIV-UHFFFAOYSA-N 3-methyl-n-[4-(2-phenylimidazol-1-yl)pyrimidin-2-yl]-1,2-oxazol-5-amine Chemical compound O1N=C(C)C=C1NC1=NC=CC(N2C(=NC=C2)C=2C=CC=CC=2)=N1 XTKPPFQBRFSEIV-UHFFFAOYSA-N 0.000 claims description 5
- DVZRCIHWWHNWKI-UHFFFAOYSA-N 4-(2-phenylimidazol-1-yl)-n-[3-(trifluoromethyl)phenyl]pyrimidin-2-amine Chemical compound FC(F)(F)C1=CC=CC(NC=2N=C(C=CN=2)N2C(=NC=C2)C=2C=CC=CC=2)=C1 DVZRCIHWWHNWKI-UHFFFAOYSA-N 0.000 claims description 5
- 206010027202 Meningitis bacterial Diseases 0.000 claims description 5
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 claims description 5
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 claims description 5
- 201000009904 bacterial meningitis Diseases 0.000 claims description 5
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims description 5
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims description 5
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 5
- AAVVJYRIFZWOQJ-UHFFFAOYSA-N n-(3,5-dimethylphenyl)-4-(2-phenylimidazol-1-yl)pyrimidin-2-amine Chemical compound CC1=CC(C)=CC(NC=2N=C(C=CN=2)N2C(=NC=C2)C=2C=CC=CC=2)=C1 AAVVJYRIFZWOQJ-UHFFFAOYSA-N 0.000 claims description 5
- IZXZEYNCDVNMCQ-UHFFFAOYSA-N n-(3-chlorophenyl)-4-(2-phenylimidazol-1-yl)pyrimidin-2-amine Chemical compound ClC1=CC=CC(NC=2N=C(C=CN=2)N2C(=NC=C2)C=2C=CC=CC=2)=C1 IZXZEYNCDVNMCQ-UHFFFAOYSA-N 0.000 claims description 5
- 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 claims description 5
- PSWWUMTWJRPKLC-UHFFFAOYSA-N n-[3-methyl-5-(trifluoromethyl)phenyl]-4-(2-phenylimidazol-1-yl)pyrimidin-2-amine Chemical compound FC(F)(F)C1=CC(C)=CC(NC=2N=C(C=CN=2)N2C(=NC=C2)C=2C=CC=CC=2)=C1 PSWWUMTWJRPKLC-UHFFFAOYSA-N 0.000 claims description 5
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 5
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- 238000001959 radiotherapy Methods 0.000 claims description 5
- 229940075993 receptor modulator Drugs 0.000 claims description 5
- 230000004276 retinal vascularization Effects 0.000 claims description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
- DSBLOQJREHHYBA-UHFFFAOYSA-N 1-[4-[[3-methyl-5-[[4-(2-phenylimidazol-1-yl)pyrimidin-2-yl]amino]phenyl]methyl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1CC1=CC(C)=CC(NC=2N=C(C=CN=2)N2C(=NC=C2)C=2C=CC=CC=2)=C1 DSBLOQJREHHYBA-UHFFFAOYSA-N 0.000 claims description 4
- AJDQTJYEJBYYOB-UHFFFAOYSA-N 4-(2-aminoimidazol-1-yl)-n-(3,5-dimethylphenyl)pyrimidin-2-amine Chemical compound CC1=CC(C)=CC(NC=2N=C(C=CN=2)N2C(=NC=C2)N)=C1 AJDQTJYEJBYYOB-UHFFFAOYSA-N 0.000 claims description 4
- 208000022873 Ocular disease Diseases 0.000 claims description 4
- UIRKNQLZZXALBI-MSVGPLKSSA-N Squalamine Chemical compound C([C@@H]1C[C@H]2O)[C@@H](NCCCNCCCCN)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@H](C)CC[C@H](C(C)C)OS(O)(=O)=O)[C@@]2(C)CC1 UIRKNQLZZXALBI-MSVGPLKSSA-N 0.000 claims description 4
- UIRKNQLZZXALBI-UHFFFAOYSA-N Squalamine Natural products OC1CC2CC(NCCCNCCCCN)CCC2(C)C2C1C1CCC(C(C)CCC(C(C)C)OS(O)(=O)=O)C1(C)CC2 UIRKNQLZZXALBI-UHFFFAOYSA-N 0.000 claims description 4
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 claims description 4
- OHPOATZAMKEIIC-UHFFFAOYSA-N n-(1-oxidopyridin-1-ium-3-yl)-4-(2-phenylimidazol-1-yl)pyrimidin-2-amine Chemical compound [O-][N+]1=CC=CC(NC=2N=C(C=CN=2)N2C(=NC=C2)C=2C=CC=CC=2)=C1 OHPOATZAMKEIIC-UHFFFAOYSA-N 0.000 claims description 4
- BYRNMOWWARMRSW-UHFFFAOYSA-N n-(2-fluorophenyl)-4-(2-phenylimidazol-1-yl)pyrimidin-2-amine Chemical compound FC1=CC=CC=C1NC1=NC=CC(N2C(=NC=C2)C=2C=CC=CC=2)=N1 BYRNMOWWARMRSW-UHFFFAOYSA-N 0.000 claims description 4
- OXEHMUYZPDSYHE-UHFFFAOYSA-N n-(2-methoxyphenyl)-4-(2-phenylimidazol-1-yl)pyrimidin-2-amine Chemical compound COC1=CC=CC=C1NC1=NC=CC(N2C(=NC=C2)C=2C=CC=CC=2)=N1 OXEHMUYZPDSYHE-UHFFFAOYSA-N 0.000 claims description 4
- PRMOKNGXXJPBMD-UHFFFAOYSA-N n-(3,5-dichlorophenyl)-4-(2-phenylimidazol-1-yl)pyrimidin-2-amine Chemical compound ClC1=CC(Cl)=CC(NC=2N=C(C=CN=2)N2C(=NC=C2)C=2C=CC=CC=2)=C1 PRMOKNGXXJPBMD-UHFFFAOYSA-N 0.000 claims description 4
- BKTXUKGSIOCCOG-UHFFFAOYSA-N n-(3,5-dimethylphenyl)-4-(2-pyridin-2-ylimidazol-1-yl)pyrimidin-2-amine Chemical compound CC1=CC(C)=CC(NC=2N=C(C=CN=2)N2C(=NC=C2)C=2N=CC=CC=2)=C1 BKTXUKGSIOCCOG-UHFFFAOYSA-N 0.000 claims description 4
- ZQFFEUAQGFFMDA-UHFFFAOYSA-N n-(3,5-dimethylphenyl)-4-(2-pyridin-3-ylimidazol-1-yl)pyrimidin-2-amine Chemical compound CC1=CC(C)=CC(NC=2N=C(C=CN=2)N2C(=NC=C2)C=2C=NC=CC=2)=C1 ZQFFEUAQGFFMDA-UHFFFAOYSA-N 0.000 claims description 4
- CAKCSRYUEXZENU-UHFFFAOYSA-N n-(3,5-dimethylphenyl)-4-(4-methyl-2-phenylimidazol-1-yl)pyrimidin-2-amine Chemical compound N=1C(C)=CN(C=2N=C(NC=3C=C(C)C=C(C)C=3)N=CC=2)C=1C1=CC=CC=C1 CAKCSRYUEXZENU-UHFFFAOYSA-N 0.000 claims description 4
- FAGREBOKSNRJQA-UHFFFAOYSA-N n-(3-methylphenyl)-4-(2-phenylimidazol-1-yl)pyrimidin-2-amine Chemical compound CC1=CC=CC(NC=2N=C(C=CN=2)N2C(=NC=C2)C=2C=CC=CC=2)=C1 FAGREBOKSNRJQA-UHFFFAOYSA-N 0.000 claims description 4
- OSAOACVWVSACAV-UHFFFAOYSA-N n-(4-chlorophenyl)-4-(2-phenylimidazol-1-yl)pyrimidin-2-amine Chemical compound C1=CC(Cl)=CC=C1NC1=NC=CC(N2C(=NC=C2)C=2C=CC=CC=2)=N1 OSAOACVWVSACAV-UHFFFAOYSA-N 0.000 claims description 4
- QEDGWRJJPHEGPB-UHFFFAOYSA-N n-(4-methoxyphenyl)-4-(2-phenylimidazol-1-yl)pyrimidin-2-amine Chemical compound C1=CC(OC)=CC=C1NC1=NC=CC(N2C(=NC=C2)C=2C=CC=CC=2)=N1 QEDGWRJJPHEGPB-UHFFFAOYSA-N 0.000 claims description 4
- DLZXGSGXNXHCOD-UHFFFAOYSA-N n-(4-methylphenyl)-4-(2-phenylimidazol-1-yl)pyrimidin-2-amine Chemical compound C1=CC(C)=CC=C1NC1=NC=CC(N2C(=NC=C2)C=2C=CC=CC=2)=N1 DLZXGSGXNXHCOD-UHFFFAOYSA-N 0.000 claims description 4
- ACKTUROCWZUCCX-UHFFFAOYSA-N n-[4-(2-phenylimidazol-1-yl)pyrimidin-2-yl]-1,2-oxazol-3-amine Chemical compound N=1C=CC(N2C(=NC=C2)C=2C=CC=CC=2)=NC=1NC=1C=CON=1 ACKTUROCWZUCCX-UHFFFAOYSA-N 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 230000007170 pathology Effects 0.000 claims description 4
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 claims description 4
- 229960004622 raloxifene Drugs 0.000 claims description 4
- 229950001248 squalamine Drugs 0.000 claims description 4
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 claims description 3
- DLTOFUFMWGQCLV-UHFFFAOYSA-N 5-methyl-n-[4-(2-phenylimidazol-1-yl)pyrimidin-2-yl]-1,3,4-thiadiazol-2-amine Chemical compound S1C(C)=NN=C1NC1=NC=CC(N2C(=NC=C2)C=2C=CC=CC=2)=N1 DLTOFUFMWGQCLV-UHFFFAOYSA-N 0.000 claims description 3
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 claims description 3
- 108010079709 Angiostatins Proteins 0.000 claims description 3
- 206010006187 Breast cancer Diseases 0.000 claims description 3
- 208000026310 Breast neoplasm Diseases 0.000 claims description 3
- HVXBOLULGPECHP-WAYWQWQTSA-N Combretastatin A4 Chemical compound C1=C(O)C(OC)=CC=C1\C=C/C1=CC(OC)=C(OC)C(OC)=C1 HVXBOLULGPECHP-WAYWQWQTSA-N 0.000 claims description 3
- 206010012442 Dermatitis contact Diseases 0.000 claims description 3
- 102000006992 Interferon-alpha Human genes 0.000 claims description 3
- 108010047761 Interferon-alpha Proteins 0.000 claims description 3
- 102000013462 Interleukin-12 Human genes 0.000 claims description 3
- 108010065805 Interleukin-12 Proteins 0.000 claims description 3
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 claims description 3
- 229930012538 Paclitaxel Natural products 0.000 claims description 3
- 206010041067 Small cell lung cancer Diseases 0.000 claims description 3
- FZCSTZYAHCUGEM-UHFFFAOYSA-N aspergillomarasmine B Natural products OC(=O)CNC(C(O)=O)CNC(C(O)=O)CC(O)=O FZCSTZYAHCUGEM-UHFFFAOYSA-N 0.000 claims description 3
- 210000000988 bone and bone Anatomy 0.000 claims description 3
- 210000004556 brain Anatomy 0.000 claims description 3
- 201000008275 breast carcinoma Diseases 0.000 claims description 3
- WNRZHQBJSXRYJK-UHFFFAOYSA-N carboxyamidotriazole Chemical compound NC1=C(C(=O)N)N=NN1CC(C=C1Cl)=CC(Cl)=C1C(=O)C1=CC=C(Cl)C=C1 WNRZHQBJSXRYJK-UHFFFAOYSA-N 0.000 claims description 3
- 229960005537 combretastatin A-4 Drugs 0.000 claims description 3
- HVXBOLULGPECHP-UHFFFAOYSA-N combretastatin A4 Natural products C1=C(O)C(OC)=CC=C1C=CC1=CC(OC)=C(OC)C(OC)=C1 HVXBOLULGPECHP-UHFFFAOYSA-N 0.000 claims description 3
- 208000010247 contact dermatitis Diseases 0.000 claims description 3
- 229940111134 coxibs Drugs 0.000 claims description 3
- 229940117681 interleukin-12 Drugs 0.000 claims description 3
- 210000000867 larynx Anatomy 0.000 claims description 3
- 210000004072 lung Anatomy 0.000 claims description 3
- 201000005249 lung adenocarcinoma Diseases 0.000 claims description 3
- 210000004324 lymphatic system Anatomy 0.000 claims description 3
- QPWLEFJRGRXTNN-UHFFFAOYSA-N n-(2,6-dimethylpyridin-4-yl)-4-(2-phenylimidazol-1-yl)pyrimidin-2-amine Chemical compound CC1=NC(C)=CC(NC=2N=C(C=CN=2)N2C(=NC=C2)C=2C=CC=CC=2)=C1 QPWLEFJRGRXTNN-UHFFFAOYSA-N 0.000 claims description 3
- HMTILXUALIYSDB-UHFFFAOYSA-N n-(3,5-difluorophenyl)-4-(2-phenylimidazol-1-yl)pyrimidin-2-amine Chemical compound FC1=CC(F)=CC(NC=2N=C(C=CN=2)N2C(=NC=C2)C=2C=CC=CC=2)=C1 HMTILXUALIYSDB-UHFFFAOYSA-N 0.000 claims description 3
- MHHCPQUFBADOGH-UHFFFAOYSA-N n-(3,5-dimethoxyphenyl)-4-(2-phenylimidazol-1-yl)pyrimidin-2-amine Chemical compound COC1=CC(OC)=CC(NC=2N=C(C=CN=2)N2C(=NC=C2)C=2C=CC=CC=2)=C1 MHHCPQUFBADOGH-UHFFFAOYSA-N 0.000 claims description 3
- ZNFSFDXPGWJMME-UHFFFAOYSA-N n-[3,5-bis(trifluoromethyl)phenyl]-4-(2-phenylimidazol-1-yl)pyrimidin-2-amine Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(NC=2N=C(C=CN=2)N2C(=NC=C2)C=2C=CC=CC=2)=C1 ZNFSFDXPGWJMME-UHFFFAOYSA-N 0.000 claims description 3
- 201000008482 osteoarthritis Diseases 0.000 claims description 3
- 201000008968 osteosarcoma Diseases 0.000 claims description 3
- 229960001592 paclitaxel Drugs 0.000 claims description 3
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 3
- 229940043138 pentosan polysulfate Drugs 0.000 claims description 3
- 239000002599 prostaglandin synthase inhibitor Substances 0.000 claims description 3
- 201000006845 reticulosarcoma Diseases 0.000 claims description 3
- 208000029922 reticulum cell sarcoma Diseases 0.000 claims description 3
- 208000007442 rickets Diseases 0.000 claims description 3
- 208000000587 small cell lung carcinoma Diseases 0.000 claims description 3
- 210000002784 stomach Anatomy 0.000 claims description 3
- 229960001603 tamoxifen Drugs 0.000 claims description 3
- 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 claims description 3
- 229960003433 thalidomide Drugs 0.000 claims description 3
- 229960000575 trastuzumab Drugs 0.000 claims description 3
- 208000027930 type IV hypersensitivity disease Diseases 0.000 claims description 3
- RNVBUDDBEAXNJS-UHFFFAOYSA-N 4-(2-cyclopropylimidazol-1-yl)-n-(3,5-dimethylphenyl)pyrimidin-2-amine Chemical compound CC1=CC(C)=CC(NC=2N=C(C=CN=2)N2C(=NC=C2)C2CC2)=C1 RNVBUDDBEAXNJS-UHFFFAOYSA-N 0.000 claims description 2
- 229940122204 Cyclooxygenase inhibitor Drugs 0.000 claims description 2
- 229940124761 MMP inhibitor Drugs 0.000 claims description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 claims description 2
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 claims description 2
- 230000002490 cerebral effect Effects 0.000 claims description 2
- 230000000302 ischemic effect Effects 0.000 claims description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
- MQWJQLYEDINRLP-UHFFFAOYSA-N n-(3,5-dimethoxyphenyl)-2-(2-phenylimidazol-1-yl)-1h-pyrimidin-2-amine Chemical compound COC1=CC(OC)=CC(NC2(N=CC=CN2)N2C(=NC=C2)C=2C=CC=CC=2)=C1 MQWJQLYEDINRLP-UHFFFAOYSA-N 0.000 claims description 2
- QPFWVFPJLHQHCT-UHFFFAOYSA-N n-(3,5-dimethylphenyl)-4-(2-methylimidazol-1-yl)pyrimidin-2-amine Chemical compound CC1=NC=CN1C1=CC=NC(NC=2C=C(C)C=C(C)C=2)=N1 QPFWVFPJLHQHCT-UHFFFAOYSA-N 0.000 claims description 2
- RGQCKSICTLMEDR-UHFFFAOYSA-N n-(3-methoxyphenyl)-4-(2-phenylimidazol-1-yl)pyrimidin-2-amine Chemical compound COC1=CC=CC(NC=2N=C(C=CN=2)N2C(=NC=C2)C=2C=CC=CC=2)=C1 RGQCKSICTLMEDR-UHFFFAOYSA-N 0.000 claims description 2
- RIBKAXROSUQPJP-UHFFFAOYSA-N n-(4-fluorophenyl)-4-(2-phenylimidazol-1-yl)pyrimidin-2-amine Chemical compound C1=CC(F)=CC=C1NC1=NC=CC(N2C(=NC=C2)C=2C=CC=CC=2)=N1 RIBKAXROSUQPJP-UHFFFAOYSA-N 0.000 claims description 2
- IILYFABNAOBIQH-UHFFFAOYSA-N n-[4-(2-phenylimidazol-1-yl)pyrimidin-2-yl]-1,3,4-thiadiazol-2-amine Chemical compound N=1C=CC(N2C(=NC=C2)C=2C=CC=CC=2)=NC=1NC1=NN=CS1 IILYFABNAOBIQH-UHFFFAOYSA-N 0.000 claims description 2
- 201000002528 pancreatic cancer Diseases 0.000 claims description 2
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 2
- COKMIXFXJJXBQG-NRFANRHFSA-N tirofiban Chemical group C1=CC(C[C@H](NS(=O)(=O)CCCC)C(O)=O)=CC=C1OCCCCC1CCNCC1 COKMIXFXJJXBQG-NRFANRHFSA-N 0.000 claims description 2
- 229960003425 tirofiban Drugs 0.000 claims description 2
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 claims description 2
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 claims 3
- CYTHOJJDWBEAMO-UHFFFAOYSA-N 4-(2-phenylimidazol-1-yl)-n-pyridin-4-ylpyrimidin-2-amine Chemical compound N=1C=CC(N2C(=NC=C2)C=2C=CC=CC=2)=NC=1NC1=CC=NC=C1 CYTHOJJDWBEAMO-UHFFFAOYSA-N 0.000 claims 1
- 102000012936 Angiostatins Human genes 0.000 claims 1
- JFROSSFDGZJGNE-UHFFFAOYSA-N n-(3,5-dimethylphenyl)-4-(2-pyrimidin-5-ylimidazol-1-yl)pyrimidin-2-amine Chemical compound CC1=CC(C)=CC(NC=2N=C(C=CN=2)N2C(=NC=C2)C=2C=NC=NC=2)=C1 JFROSSFDGZJGNE-UHFFFAOYSA-N 0.000 claims 1
- NCDQVNREMKGQJM-UHFFFAOYSA-N n-(3-fluorophenyl)-4-(2-phenylimidazol-1-yl)pyrimidin-2-amine Chemical compound FC1=CC=CC(NC=2N=C(C=CN=2)N2C(=NC=C2)C=2C=CC=CC=2)=C1 NCDQVNREMKGQJM-UHFFFAOYSA-N 0.000 claims 1
- 230000004614 tumor growth Effects 0.000 abstract description 8
- 230000019491 signal transduction Effects 0.000 abstract description 7
- 201000001320 Atherosclerosis Diseases 0.000 abstract description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 58
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 40
- 239000007787 solid Substances 0.000 description 38
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 37
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 32
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 32
- 210000004027 cell Anatomy 0.000 description 28
- 239000000243 solution Substances 0.000 description 28
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 25
- 102000004190 Enzymes Human genes 0.000 description 22
- 108090000790 Enzymes Proteins 0.000 description 22
- 229940088598 enzyme Drugs 0.000 description 22
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 21
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 21
- 238000003556 assay Methods 0.000 description 21
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
- 235000019439 ethyl acetate Nutrition 0.000 description 18
- 238000003818 flash chromatography Methods 0.000 description 18
- 102000005962 receptors Human genes 0.000 description 18
- 108020003175 receptors Proteins 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 17
- 238000010438 heat treatment Methods 0.000 description 17
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 17
- 239000003921 oil Substances 0.000 description 16
- 239000011541 reaction mixture Substances 0.000 description 16
- 238000000746 purification Methods 0.000 description 15
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 13
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- 101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 description 12
- 125000004432 carbon atom Chemical group C* 0.000 description 12
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 11
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 11
- 235000011180 diphosphates Nutrition 0.000 description 11
- 239000011780 sodium chloride Substances 0.000 description 11
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 11
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 10
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 10
- 239000007983 Tris buffer Substances 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 229940048084 pyrophosphate Drugs 0.000 description 10
- 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 9
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 9
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
- 235000019341 magnesium sulphate Nutrition 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- 239000000758 substrate Substances 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- 101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 description 8
- 108091008605 VEGF receptors Proteins 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 8
- 239000000872 buffer Substances 0.000 description 8
- 125000004122 cyclic group Chemical group 0.000 description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 239000013024 dilution buffer Substances 0.000 description 7
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- 230000002441 reversible effect Effects 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 238000012546 transfer Methods 0.000 description 7
- XRCNGZUTHDTRNN-UHFFFAOYSA-N 2-methylsulfonyl-4-(2-phenylimidazol-1-yl)pyrimidine Chemical compound CS(=O)(=O)C1=NC=CC(N2C(=NC=C2)C=2C=CC=CC=2)=N1 XRCNGZUTHDTRNN-UHFFFAOYSA-N 0.000 description 6
- VQGHOUODWALEFC-UHFFFAOYSA-N 2-phenylpyridine Chemical compound C1=CC=CC=C1C1=CC=CC=N1 VQGHOUODWALEFC-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 108700020796 Oncogene Proteins 0.000 description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 239000012911 assay medium Substances 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 238000010790 dilution Methods 0.000 description 6
- 239000012895 dilution Substances 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 6
- 238000000021 kinase assay Methods 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 6
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 238000004007 reversed phase HPLC Methods 0.000 description 6
- 238000001665 trituration Methods 0.000 description 6
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 5
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 5
- 229910021380 Manganese Chloride Inorganic materials 0.000 description 5
- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 5
- 206010027476 Metastases Diseases 0.000 description 5
- 239000007832 Na2SO4 Substances 0.000 description 5
- 229910019142 PO4 Inorganic materials 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 5
- 102000004357 Transferases Human genes 0.000 description 5
- 108090000992 Transferases Proteins 0.000 description 5
- 125000002619 bicyclic group Chemical group 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 125000004415 heterocyclylalkyl group Chemical group 0.000 description 5
- 150000002596 lactones Chemical class 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 239000011565 manganese chloride Substances 0.000 description 5
- 235000002867 manganese chloride Nutrition 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 239000013642 negative control Substances 0.000 description 5
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 5
- 239000010452 phosphate Substances 0.000 description 5
- 239000013641 positive control Substances 0.000 description 5
- 238000001556 precipitation Methods 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- MKARNSWMMBGSHX-UHFFFAOYSA-N 3,5-dimethylaniline Chemical compound CC1=CC(C)=CC(N)=C1 MKARNSWMMBGSHX-UHFFFAOYSA-N 0.000 description 4
- GIICGIVMEFQZHH-UHFFFAOYSA-N 4-(2-chloroimidazol-1-yl)-n-(3,5-dimethylphenyl)pyrimidin-2-amine Chemical compound CC1=CC(C)=CC(NC=2N=C(C=CN=2)N2C(=NC=C2)Cl)=C1 GIICGIVMEFQZHH-UHFFFAOYSA-N 0.000 description 4
- LCBHDOKYJVFFBW-UHFFFAOYSA-N 4-(2-phenylimidazol-1-yl)-n-pyridin-3-ylpyrimidin-2-amine Chemical compound N=1C=CC(N2C(=NC=C2)C=2C=CC=CC=2)=NC=1NC1=CC=CN=C1 LCBHDOKYJVFFBW-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 4
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 206010029113 Neovascularisation Diseases 0.000 description 4
- 108091000080 Phosphotransferase Proteins 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 4
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 150000002148 esters Chemical group 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 239000006260 foam Substances 0.000 description 4
- 230000014509 gene expression Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 230000009401 metastasis Effects 0.000 description 4
- 230000002297 mitogenic effect Effects 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 4
- 102000020233 phosphotransferase Human genes 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 4
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- 210000003556 vascular endothelial cell Anatomy 0.000 description 4
- VTPIDSDCVCXYRO-UHFFFAOYSA-N 1-[4-[[3-[[4-(2-phenylimidazol-1-yl)pyrimidin-2-yl]amino]phenyl]methyl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1CC1=CC=CC(NC=2N=C(C=CN=2)N2C(=NC=C2)C=2C=CC=CC=2)=C1 VTPIDSDCVCXYRO-UHFFFAOYSA-N 0.000 description 3
- PKDPUENCROCRCH-UHFFFAOYSA-N 1-piperazin-1-ylethanone Chemical compound CC(=O)N1CCNCC1 PKDPUENCROCRCH-UHFFFAOYSA-N 0.000 description 3
- BXXRKGPQORBVRU-UHFFFAOYSA-N 2-(3,5-dimethylanilino)-1h-pyrimidin-6-one Chemical compound CC1=CC(C)=CC(NC=2NC(=O)C=CN=2)=C1 BXXRKGPQORBVRU-UHFFFAOYSA-N 0.000 description 3
- LYUAPIFUSUJZFL-UHFFFAOYSA-N 2-chloro-4-(2-phenylimidazol-1-yl)pyrimidine Chemical compound ClC1=NC=CC(N2C(=NC=C2)C=2C=CC=CC=2)=N1 LYUAPIFUSUJZFL-UHFFFAOYSA-N 0.000 description 3
- FKACHUDGNZNGGU-UHFFFAOYSA-N 2-phenyl-5-(trifluoromethyl)pyridine Chemical compound N1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1 FKACHUDGNZNGGU-UHFFFAOYSA-N 0.000 description 3
- USVPXXUJYKAXTR-UHFFFAOYSA-N 4-(2-phenylimidazol-1-yl)-n-pyrazin-2-ylpyrimidin-2-amine Chemical compound N=1C=CC(N2C(=NC=C2)C=2C=CC=CC=2)=NC=1NC1=CN=CC=N1 USVPXXUJYKAXTR-UHFFFAOYSA-N 0.000 description 3
- QOYSFLRSTRMMPG-UHFFFAOYSA-N 4-(2-phenylimidazol-1-yl)-n-pyrimidin-2-ylpyrimidin-2-amine Chemical compound N=1C=CC(N2C(=NC=C2)C=2C=CC=CC=2)=NC=1NC1=NC=CC=N1 QOYSFLRSTRMMPG-UHFFFAOYSA-N 0.000 description 3
- 108010039627 Aprotinin Proteins 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 108010070675 Glutathione transferase Proteins 0.000 description 3
- 102100029100 Hematopoietic prostaglandin D synthase Human genes 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 3
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 208000034038 Pathologic Neovascularization Diseases 0.000 description 3
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 3
- 102000001332 SRC Human genes 0.000 description 3
- 108060006706 SRC Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229920004890 Triton X-100 Polymers 0.000 description 3
- 239000013504 Triton X-100 Substances 0.000 description 3
- 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 3
- 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 125000003342 alkenyl group Chemical group 0.000 description 3
- 125000000304 alkynyl group Chemical group 0.000 description 3
- 229960004405 aprotinin Drugs 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- VIHAEDVKXSOUAT-UHFFFAOYSA-N but-2-en-4-olide Chemical compound O=C1OCC=C1 VIHAEDVKXSOUAT-UHFFFAOYSA-N 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 210000002889 endothelial cell Anatomy 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- JVZRCNQLWOELDU-UHFFFAOYSA-N gamma-Phenylpyridine Natural products C1=CC=CC=C1C1=CC=NC=C1 JVZRCNQLWOELDU-UHFFFAOYSA-N 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 3
- 229940015043 glyoxal Drugs 0.000 description 3
- 238000010348 incorporation Methods 0.000 description 3
- 125000001041 indolyl group Chemical group 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 108010052968 leupeptin Proteins 0.000 description 3
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 3
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 3
- 239000012139 lysis buffer Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- FSSRJBLZRYMFLQ-UHFFFAOYSA-N n-(3,5-dimethylphenyl)-4-[2-(3-fluorophenyl)imidazol-1-yl]pyrimidin-2-amine Chemical compound CC1=CC(C)=CC(NC=2N=C(C=CN=2)N2C(=NC=C2)C=2C=C(F)C=CC=2)=C1 FSSRJBLZRYMFLQ-UHFFFAOYSA-N 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 108010091212 pepstatin Proteins 0.000 description 3
- 229950000964 pepstatin Drugs 0.000 description 3
- FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 125000002098 pyridazinyl group Chemical group 0.000 description 3
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridine hydrochloride Substances [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 3
- RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 229960002855 simvastatin Drugs 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- 239000011534 wash buffer Substances 0.000 description 3
- WOANRKPFIPNPRV-UHFFFAOYSA-N (3-amino-5-methylphenyl)methanol Chemical compound CC1=CC(N)=CC(CO)=C1 WOANRKPFIPNPRV-UHFFFAOYSA-N 0.000 description 2
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 2
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 2
- LBQKKAJFYZWDQS-UHFFFAOYSA-N 1-[4-[(3-amino-5-methylphenyl)methyl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1CC1=CC(C)=CC(N)=C1 LBQKKAJFYZWDQS-UHFFFAOYSA-N 0.000 description 2
- YNBSVMAJDLBHTO-UHFFFAOYSA-N 1-[4-[(3-aminophenyl)methyl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1CC1=CC=CC(N)=C1 YNBSVMAJDLBHTO-UHFFFAOYSA-N 0.000 description 2
- RRQYJINTUHWNHW-UHFFFAOYSA-N 1-ethoxy-2-(2-ethoxyethoxy)ethane Chemical compound CCOCCOCCOCC RRQYJINTUHWNHW-UHFFFAOYSA-N 0.000 description 2
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 2
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 2
- ZCUJYXPAKHMBAZ-UHFFFAOYSA-N 2-phenyl-1h-imidazole Chemical compound C1=CNC(C=2C=CC=CC=2)=N1 ZCUJYXPAKHMBAZ-UHFFFAOYSA-N 0.000 description 2
- WTOORHANEMAYPO-UHFFFAOYSA-N 3-(1-cyclopropylethoxy)-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C1CC1C(C)OC(C(OC1(C)C)=O)=C1C1=CC=C(S(C)(=O)=O)C=C1 WTOORHANEMAYPO-UHFFFAOYSA-N 0.000 description 2
- PQYQDILXYJVMIB-UHFFFAOYSA-N 3-(5-chloropyridin-3-yl)oxy-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=CN=CC(Cl)=C1 PQYQDILXYJVMIB-UHFFFAOYSA-N 0.000 description 2
- LMLFEGOVAVFUJS-UHFFFAOYSA-N 3-[[tert-butyl(dimethyl)silyl]oxymethyl]-5-methylaniline Chemical compound CC1=CC(N)=CC(CO[Si](C)(C)C(C)(C)C)=C1 LMLFEGOVAVFUJS-UHFFFAOYSA-N 0.000 description 2
- CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 2
- ODMFAWSYJZTWDO-UHFFFAOYSA-N 4-(2-phenylimidazol-1-yl)-n-pyrimidin-4-ylpyrimidin-2-amine Chemical compound N=1C=CC(N2C(=NC=C2)C=2C=CC=CC=2)=NC=1NC1=CC=NC=N1 ODMFAWSYJZTWDO-UHFFFAOYSA-N 0.000 description 2
- ONJHHYBWKLDIFI-UHFFFAOYSA-N 5,5-dimethyl-4-(4-methylsulfonylphenyl)-3-propan-2-yloxyfuran-2-one Chemical compound CC1(C)OC(=O)C(OC(C)C)=C1C1=CC=C(S(C)(=O)=O)C=C1 ONJHHYBWKLDIFI-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 102400000068 Angiostatin Human genes 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 201000004569 Blindness Diseases 0.000 description 2
- 208000006386 Bone Resorption Diseases 0.000 description 2
- 208000005623 Carcinogenesis Diseases 0.000 description 2
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 108010024636 Glutathione Proteins 0.000 description 2
- 229940122440 HIV protease inhibitor Drugs 0.000 description 2
- 229910004373 HOAc Inorganic materials 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 102000043276 Oncogene Human genes 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 102100038277 Prostaglandin G/H synthase 1 Human genes 0.000 description 2
- 108050003243 Prostaglandin G/H synthase 1 Proteins 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 108010034265 Vascular Endothelial Growth Factor Receptors Proteins 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 230000002491 angiogenic effect Effects 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 2
- 230000008499 blood brain barrier function Effects 0.000 description 2
- 210000001218 blood-brain barrier Anatomy 0.000 description 2
- 230000024279 bone resorption Effects 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 230000036952 cancer formation Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 231100000504 carcinogenesis Toxicity 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000006037 cell lysis Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 229960005110 cerivastatin Drugs 0.000 description 2
- SEERZIQQUAZTOL-ANMDKAQQSA-N cerivastatin Chemical compound COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 SEERZIQQUAZTOL-ANMDKAQQSA-N 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 125000002944 cyanoaryl group Chemical group 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 229960000975 daunorubicin Drugs 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 125000003106 haloaryl group Chemical group 0.000 description 2
- 239000004030 hiv protease inhibitor Substances 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 229960002367 lasofoxifene Drugs 0.000 description 2
- GXESHMAMLJKROZ-IAPPQJPRSA-N lasofoxifene Chemical compound C1([C@@H]2[C@@H](C3=CC=C(C=C3CC2)O)C=2C=CC(OCCN3CCCC3)=CC=2)=CC=CC=C1 GXESHMAMLJKROZ-IAPPQJPRSA-N 0.000 description 2
- 229960004844 lovastatin Drugs 0.000 description 2
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 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
- 230000003228 microsomal effect Effects 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 230000008747 mitogenic response Effects 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- HVMLRZOTPVNECO-UHFFFAOYSA-N n-(2-methylpyridin-4-yl)-4-(2-phenylimidazol-1-yl)pyrimidin-2-amine Chemical compound C1=NC(C)=CC(NC=2N=C(C=CN=2)N2C(=NC=C2)C=2C=CC=CC=2)=C1 HVMLRZOTPVNECO-UHFFFAOYSA-N 0.000 description 2
- NQDJXKOVJZTUJA-UHFFFAOYSA-N nevirapine Chemical compound C12=NC=CC=C2C(=O)NC=2C(C)=CC=NC=2N1C1CC1 NQDJXKOVJZTUJA-UHFFFAOYSA-N 0.000 description 2
- 238000011580 nude mouse model Methods 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- 239000008177 pharmaceutical agent Substances 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 229920002643 polyglutamic acid Polymers 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 2
- 239000011535 reaction buffer Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 210000001525 retina Anatomy 0.000 description 2
- 229940095743 selective estrogen receptor modulator Drugs 0.000 description 2
- 239000000333 selective estrogen receptor modulator Substances 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 235000017550 sodium carbonate Nutrition 0.000 description 2
- FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 description 2
- 229940048086 sodium pyrophosphate Drugs 0.000 description 2
- NSFFYSQTVOCNLX-JKIHJDPOSA-M sodium;[(2r,3s,4s,5r)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl octadecyl phosphate;hydrate Chemical compound O.[Na+].O[C@H]1[C@H](O)[C@@H](COP([O-])(=O)OCCCCCCCCCCCCCCCCCC)O[C@H]1N1C(=O)N=C(N)C=C1 NSFFYSQTVOCNLX-JKIHJDPOSA-M 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000012089 stop solution Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- BGUROAVRGXBDAD-UHFFFAOYSA-N tert-butyl n-(3-formyl-5-methylphenyl)carbamate Chemical compound CC1=CC(NC(=O)OC(C)(C)C)=CC(C=O)=C1 BGUROAVRGXBDAD-UHFFFAOYSA-N 0.000 description 2
- XOLLMKJHDWDTSL-UHFFFAOYSA-N tert-butyl n-[3-(hydroxymethyl)-5-methylphenyl]carbamate Chemical compound CC1=CC(CO)=CC(NC(=O)OC(C)(C)C)=C1 XOLLMKJHDWDTSL-UHFFFAOYSA-N 0.000 description 2
- 235000019818 tetrasodium diphosphate Nutrition 0.000 description 2
- 239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 210000003606 umbilical vein Anatomy 0.000 description 2
- 241000701447 unidentified baculovirus Species 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- BMKDZUISNHGIBY-ZETCQYMHSA-N (+)-dexrazoxane Chemical compound C([C@H](C)N1CC(=O)NC(=O)C1)N1CC(=O)NC(=O)C1 BMKDZUISNHGIBY-ZETCQYMHSA-N 0.000 description 1
- DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 description 1
- JKFZMIQMKFWJAY-RQJQXFIZSA-N (1r,3s,5z)-5-[(2e)-2-[(3as,7as)-1-[(2r)-6-hydroxy-6-methylhept-4-yn-2-yl]-7a-methyl-3a,5,6,7-tetrahydro-3h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C1(/[C@@H]2CC=C([C@]2(CCC1)C)[C@@H](CC#CC(C)(C)O)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C JKFZMIQMKFWJAY-RQJQXFIZSA-N 0.000 description 1
- USYHIIHUJPBCQG-UHFFFAOYSA-N (2-chloroacetyl)-[5-methoxy-4-[2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-yl]carbamic acid Chemical compound O1C(CC=C(C)C)C1(C)C1C(OC)C(N(C(O)=O)C(=O)CCl)CCC21CO2 USYHIIHUJPBCQG-UHFFFAOYSA-N 0.000 description 1
- XTYSXGHMTNTKFH-BDEHJDMKSA-N (2s)-1-[(2s,4r)-4-benzyl-2-hydroxy-5-[[(1s,2r)-2-hydroxy-2,3-dihydro-1h-inden-1-yl]amino]-5-oxopentyl]-n-tert-butyl-4-(pyridin-3-ylmethyl)piperazine-2-carboxamide;hydrate Chemical compound O.C([C@H](N(CC1)C[C@@H](O)C[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H]2C3=CC=CC=C3C[C@H]2O)C(=O)NC(C)(C)C)N1CC1=CC=CN=C1 XTYSXGHMTNTKFH-BDEHJDMKSA-N 0.000 description 1
- ZUQBAQVRAURMCL-DOMZBBRYSA-N (2s)-2-[[4-[2-[(6r)-2-amino-4-oxo-5,6,7,8-tetrahydro-1h-pyrido[2,3-d]pyrimidin-6-yl]ethyl]benzoyl]amino]pentanedioic acid Chemical compound C([C@@H]1CC=2C(=O)N=C(NC=2NC1)N)CC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 ZUQBAQVRAURMCL-DOMZBBRYSA-N 0.000 description 1
- XSAKVDNHFRWJKS-IIZANFQQSA-N (2s)-n-benzyl-1-[(2s)-1-[(2s)-2-[[(2s)-2-[[(2s)-2-(dimethylamino)-3-methylbutanoyl]amino]-3-methylbutanoyl]-methylamino]-3-methylbutanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carboxamide Chemical compound CC(C)[C@H](N(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC=2C=CC=CC=2)CCC1 XSAKVDNHFRWJKS-IIZANFQQSA-N 0.000 description 1
- PSVUJBVBCOISSP-SPFKKGSWSA-N (2s,3r,4s,5s,6r)-2-bis(2-chloroethylamino)phosphoryloxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound OC[C@H]1O[C@@H](OP(=O)(NCCCl)NCCCl)[C@H](O)[C@@H](O)[C@@H]1O PSVUJBVBCOISSP-SPFKKGSWSA-N 0.000 description 1
- KNXQDJCZSVHEIW-UHFFFAOYSA-N (3-fluorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(F)=C1 KNXQDJCZSVHEIW-UHFFFAOYSA-N 0.000 description 1
- CUFQBQOBLVLKRF-RZDMPUFOSA-N (4r)-3-[(2s,3s)-2-hydroxy-3-[(3-hydroxy-2-methylbenzoyl)amino]-4-phenylbutanoyl]-5,5-dimethyl-n-[(2-methylphenyl)methyl]-1,3-thiazolidine-4-carboxamide Chemical compound CC1=CC=CC=C1CNC(=O)[C@@H]1C(C)(C)SCN1C(=O)[C@@H](O)[C@@H](NC(=O)C=1C(=C(O)C=CC=1)C)CC1=CC=CC=C1 CUFQBQOBLVLKRF-RZDMPUFOSA-N 0.000 description 1
- HINZVVDZPLARRP-YSVIXOAZSA-N (4r,5s,6s,7r)-1,3-bis[(3-aminophenyl)methyl]-4,7-dibenzyl-5,6-dihydroxy-1,3-diazepan-2-one;methanesulfonic acid Chemical compound CS(O)(=O)=O.CS(O)(=O)=O.NC1=CC=CC(CN2C(N(CC=3C=C(N)C=CC=3)[C@H](CC=3C=CC=CC=3)[C@H](O)[C@@H](O)[C@H]2CC=2C=CC=CC=2)=O)=C1 HINZVVDZPLARRP-YSVIXOAZSA-N 0.000 description 1
- KISYRVKLJQJQEB-LJQANCHMSA-N (5r)-3-(5-bromopyridin-2-yl)oxy-5-ethyl-5-methyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound O([C@](C=1C=2C=CC(=CC=2)S(C)(=O)=O)(C)CC)C(=O)C=1OC1=CC=C(Br)C=N1 KISYRVKLJQJQEB-LJQANCHMSA-N 0.000 description 1
- UNYODXILNOHQKG-GOSISDBHSA-N (5r)-3-(5-bromopyridin-2-yl)oxy-5-methyl-4-(4-methylsulfonylphenyl)-5-(2,2,2-trifluoroethyl)furan-2-one Chemical compound O([C@@](C=1C=2C=CC(=CC=2)S(C)(=O)=O)(CC(F)(F)F)C)C(=O)C=1OC1=CC=C(Br)C=N1 UNYODXILNOHQKG-GOSISDBHSA-N 0.000 description 1
- ZKSNZYLCOXUJIR-VOKUKXJJSA-N (5s,5ar,8ar,9r)-5-[[(2r,4ar,6r,7r,8r,8as)-7-(dimethylamino)-8-hydroxy-2-methyl-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy]-9-(4-hydroxy-3,5-dimethoxyphenyl)-5a,6,8a,9-tetrahydro-5h-[2]benzofuro[6,5-f][1,3]benzodioxol-8-one 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)N(C)C)[C@@H]3[C@@H]2C(OC3)=O)=C1 ZKSNZYLCOXUJIR-VOKUKXJJSA-N 0.000 description 1
- DLROLUIVVKTFPW-LVEBQJTPSA-N (5s,5as,8ar,9r)-9-(4-hydroxy-3,5-dimethoxyphenyl)-5-(4-nitroanilino)-5a,6,8a,9-tetrahydro-5h-[2]benzofuro[5,6-f][1,3]benzodioxol-8-one Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](NC=3C=CC(=CC=3)[N+]([O-])=O)[C@@H]3[C@@H]2C(OC3)=O)=C1 DLROLUIVVKTFPW-LVEBQJTPSA-N 0.000 description 1
- WTSKMKRYHATLLL-UHFFFAOYSA-N (6-benzoyloxy-3-cyanopyridin-2-yl) 3-[3-(ethoxymethyl)-5-fluoro-2,6-dioxopyrimidine-1-carbonyl]benzoate Chemical compound O=C1N(COCC)C=C(F)C(=O)N1C(=O)C1=CC=CC(C(=O)OC=2C(=CC=C(OC(=O)C=3C=CC=CC=3)N=2)C#N)=C1 WTSKMKRYHATLLL-UHFFFAOYSA-N 0.000 description 1
- OPBPMGYBSDKJBT-DQHLZUIQSA-N (7s,9r,10r)-9-ethyl-4,6,9,10,11-pentahydroxy-7-[(2r,4s,5s,6s)-5-hydroxy-6-methyl-4-morpholin-4-yloxan-2-yl]oxy-8,10-dihydro-7h-tetracene-5,12-dione Chemical compound N1([C@H]2C[C@@H](O[C@@H](C)[C@H]2O)O[C@H]2C[C@]([C@@H](C3=C(O)C=4C(=O)C5=CC=CC(O)=C5C(=O)C=4C(O)=C32)O)(O)CC)CCOCC1 OPBPMGYBSDKJBT-DQHLZUIQSA-N 0.000 description 1
- BSRQHWFOFMAZRL-BODGVHBXSA-N (7s,9s)-7-[(2r,4s,5s,6s)-5-[(2s,4s,5s,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-4-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-8,10-dihydro-7h-tetracene-5,12-dione;hydron;chloride Chemical compound Cl.C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@H]1[C@@H](O)C[C@H](O[C@@H]2C3=C(O)C=4C(=O)C5=CC=CC=C5C(=O)C=4C(O)=C3C[C@](O)(C2)C(=O)CO)O[C@H]1C BSRQHWFOFMAZRL-BODGVHBXSA-N 0.000 description 1
- FPVKHBSQESCIEP-UHFFFAOYSA-N (8S)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol Natural products C1C(O)C(CO)OC1N1C(NC=NCC2O)=C2N=C1 FPVKHBSQESCIEP-UHFFFAOYSA-N 0.000 description 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
- LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical compound C([C@@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-KRWDZBQOSA-N 0.000 description 1
- ZGNLFUXWZJGETL-YUSKDDKASA-N (Z)-[(2S)-2-amino-2-carboxyethyl]-hydroxyimino-oxidoazanium Chemical compound N[C@@H](C\[N+]([O-])=N\O)C(O)=O ZGNLFUXWZJGETL-YUSKDDKASA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- 125000005940 1,4-dioxanyl group Chemical group 0.000 description 1
- HJTAZXHBEBIQQX-UHFFFAOYSA-N 1,5-bis(chloromethyl)naphthalene Chemical compound C1=CC=C2C(CCl)=CC=CC2=C1CCl HJTAZXHBEBIQQX-UHFFFAOYSA-N 0.000 description 1
- VAMFSFIPDOODFH-UHFFFAOYSA-N 1-(3,4-dichlorophenyl)-3-(2,3-dihydro-1-benzofuran-5-ylsulfonyl)urea Chemical compound C1=C(Cl)C(Cl)=CC=C1NC(=O)NS(=O)(=O)C1=CC=C(OCC2)C2=C1 VAMFSFIPDOODFH-UHFFFAOYSA-N 0.000 description 1
- MZNMZWZGUGFQJP-UHFFFAOYSA-N 1-[11-(dodecylamino)-10-hydroxyundecyl]-3,7-dimethylpurine-2,6-dione Chemical compound O=C1N(CCCCCCCCCC(O)CNCCCCCCCCCCCC)C(=O)N(C)C2=C1N(C)C=N2 MZNMZWZGUGFQJP-UHFFFAOYSA-N 0.000 description 1
- BJHCYTJNPVGSBZ-YXSASFKJSA-N 1-[4-[6-amino-5-[(Z)-methoxyiminomethyl]pyrimidin-4-yl]oxy-2-chlorophenyl]-3-ethylurea Chemical compound CCNC(=O)Nc1ccc(Oc2ncnc(N)c2\C=N/OC)cc1Cl BJHCYTJNPVGSBZ-YXSASFKJSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- XYHKNCXZYYTLRG-UHFFFAOYSA-N 1h-imidazole-2-carbaldehyde Chemical compound O=CC1=NC=CN1 XYHKNCXZYYTLRG-UHFFFAOYSA-N 0.000 description 1
- ROZCIVXTLACYNY-UHFFFAOYSA-N 2,3,4,5,6-pentafluoro-n-(3-fluoro-4-methoxyphenyl)benzenesulfonamide Chemical compound C1=C(F)C(OC)=CC=C1NS(=O)(=O)C1=C(F)C(F)=C(F)C(F)=C1F ROZCIVXTLACYNY-UHFFFAOYSA-N 0.000 description 1
- BTTNYQZNBZNDOR-UHFFFAOYSA-N 2,4-dichloropyrimidine Chemical compound ClC1=CC=NC(Cl)=N1 BTTNYQZNBZNDOR-UHFFFAOYSA-N 0.000 description 1
- 125000003870 2-(1-piperidinyl)ethoxy group Chemical group [*]OC([H])([H])C([H])([H])N1C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- MEZLBLOYRFMPAC-UHFFFAOYSA-N 2-(3,4-difluorophenoxy)-3-(4-methylsulfonylphenyl)cyclopent-2-en-1-one Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C(CCC1=O)=C1OC1=CC=C(F)C(F)=C1 MEZLBLOYRFMPAC-UHFFFAOYSA-N 0.000 description 1
- JPWYHHBGIBBALT-UHFFFAOYSA-N 2-(3,5-difluorophenoxy)-3-(4-methylsulfonylphenyl)cyclopent-2-en-1-one Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C(CCC1=O)=C1OC1=CC(F)=CC(F)=C1 JPWYHHBGIBBALT-UHFFFAOYSA-N 0.000 description 1
- XWNJMSJGJFSGRY-UHFFFAOYSA-N 2-(benzylamino)-3,7-dihydropurin-6-one Chemical compound N1C=2N=CNC=2C(=O)N=C1NCC1=CC=CC=C1 XWNJMSJGJFSGRY-UHFFFAOYSA-N 0.000 description 1
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 1
- PYZOVVQJTLOHDG-FQEVSTJZSA-N 2-[(2s)-4-methyl-3-oxo-7-(4-piperidin-4-ylpiperidine-1-carbonyl)-2,5-dihydro-1h-1,4-benzodiazepin-2-yl]acetic acid Chemical compound O=C([C@H](CC(O)=O)NC1=CC=2)N(C)CC1=CC=2C(=O)N(CC1)CCC1C1CCNCC1 PYZOVVQJTLOHDG-FQEVSTJZSA-N 0.000 description 1
- QUNOQBDEVTWCTA-UHFFFAOYSA-N 2-[2-[3-[2-(1,3-dioxobenzo[de]isoquinolin-2-yl)ethylamino]propylamino]ethyl]benzo[de]isoquinoline-1,3-dione Chemical compound C1=CC(C(=O)N(CCNCCCNCCN2C(C=3C=CC=C4C=CC=C(C=34)C2=O)=O)C2=O)=C3C2=CC=CC3=C1 QUNOQBDEVTWCTA-UHFFFAOYSA-N 0.000 description 1
- 125000005273 2-acetoxybenzoic acid group Chemical group 0.000 description 1
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
- CBIAKDAYHRWZCU-UHFFFAOYSA-N 2-bromo-4-[(6,7-dimethoxyquinazolin-4-yl)amino]phenol Chemical compound C=12C=C(OC)C(OC)=CC2=NC=NC=1NC1=CC=C(O)C(Br)=C1 CBIAKDAYHRWZCU-UHFFFAOYSA-N 0.000 description 1
- ILJKKAIQFPEIBL-UHFFFAOYSA-N 2-cyclopropyl-2-hydroxyacetonitrile Chemical compound N#CC(O)C1CC1 ILJKKAIQFPEIBL-UHFFFAOYSA-N 0.000 description 1
- WKDLAARKJYJVPG-UHFFFAOYSA-N 2-methylsulfanyl-4-(2-phenylimidazol-1-yl)pyrimidine Chemical compound CSC1=NC=CC(N2C(=NC=C2)C=2C=CC=CC=2)=N1 WKDLAARKJYJVPG-UHFFFAOYSA-N 0.000 description 1
- UYHSQVMHSFXUOA-UHFFFAOYSA-N 2-methylthiouracil Chemical compound CSC1=NC=CC(O)=N1 UYHSQVMHSFXUOA-UHFFFAOYSA-N 0.000 description 1
- 125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- FFRFGVHNKJYNOV-DOVUUNBWSA-N 3',4'-Anhydrovinblastine 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)CC)N2CCC2=C1NC1=CC=CC=C21 FFRFGVHNKJYNOV-DOVUUNBWSA-N 0.000 description 1
- KSLLHNGAEZZBKW-UHFFFAOYSA-N 3-(1,3-benzothiazol-6-yloxy)-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound CC1(C)OC(=O)C(OC=2C=C3SC=NC3=CC=2)=C1C1=CC=C(S(C)(=O)=O)C=C1 KSLLHNGAEZZBKW-UHFFFAOYSA-N 0.000 description 1
- GJJZKGZYUTXFMK-UHFFFAOYSA-N 3-(1-benzothiophen-5-yloxy)-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound CC1(C)OC(=O)C(OC=2C=C3C=CSC3=CC=2)=C1C1=CC=C(S(C)(=O)=O)C=C1 GJJZKGZYUTXFMK-UHFFFAOYSA-N 0.000 description 1
- ZQZJULZPQACTES-UHFFFAOYSA-N 3-(1h-imidazol-2-yl)pyridine Chemical compound C1=CNC(C=2C=NC=CC=2)=N1 ZQZJULZPQACTES-UHFFFAOYSA-N 0.000 description 1
- YCLVAHIPNWOMDV-UHFFFAOYSA-N 3-(2,2-dimethylpropoxy)-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound CC1(C)OC(=O)C(OCC(C)(C)C)=C1C1=CC=C(S(C)(=O)=O)C=C1 YCLVAHIPNWOMDV-UHFFFAOYSA-N 0.000 description 1
- PZOMJAGQUNQIHB-UHFFFAOYSA-N 3-(2,3-dihydro-1h-inden-1-yloxy)-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound CC1(C)OC(=O)C(OC2C3=CC=CC=C3CC2)=C1C1=CC=C(S(C)(=O)=O)C=C1 PZOMJAGQUNQIHB-UHFFFAOYSA-N 0.000 description 1
- VGLWOZUXEPKTLV-UHFFFAOYSA-N 3-(2,4-difluorophenoxy)-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=CC=C(F)C=C1F VGLWOZUXEPKTLV-UHFFFAOYSA-N 0.000 description 1
- XQSPSYSJECEBGO-UHFFFAOYSA-N 3-(3,3-dimethylcyclopentyl)oxy-5,5-dimethyl-4-(4-methylsulfonylphenyl)-2h-furan Chemical compound C1C(C)(C)CCC1OC(COC1(C)C)=C1C1=CC=C(S(C)(=O)=O)C=C1 XQSPSYSJECEBGO-UHFFFAOYSA-N 0.000 description 1
- OPUNJHWLVLIRBS-UHFFFAOYSA-N 3-(3,4-difluorobenzoyl)-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1C(=O)C1=CC=C(F)C(F)=C1 OPUNJHWLVLIRBS-UHFFFAOYSA-N 0.000 description 1
- OKKGDLZWFJTBDJ-UHFFFAOYSA-N 3-(3,4-difluorophenoxy)-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=CC=C(F)C(F)=C1 OKKGDLZWFJTBDJ-UHFFFAOYSA-N 0.000 description 1
- MEVQAQCAEVVVBK-UHFFFAOYSA-N 3-(3,4-difluorophenoxy)-5-methoxy-5-methyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(OC)(C)OC(=O)C=1OC1=CC=C(F)C(F)=C1 MEVQAQCAEVVVBK-UHFFFAOYSA-N 0.000 description 1
- PUPQHBIKTZNDCQ-UHFFFAOYSA-N 3-(3,4-difluorophenoxy)-5-methyl-4-(4-methylsulfonylphenyl)-5-propylfuran-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(CCC)(C)OC(=O)C=1OC1=CC=C(F)C(F)=C1 PUPQHBIKTZNDCQ-UHFFFAOYSA-N 0.000 description 1
- DESBNISDYNFRCI-UHFFFAOYSA-N 3-(3,5-dichloropyridin-2-yl)oxy-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=NC=C(Cl)C=C1Cl DESBNISDYNFRCI-UHFFFAOYSA-N 0.000 description 1
- ROCYHXLINRXWJW-UHFFFAOYSA-N 3-(3,5-difluorophenyl)sulfanyl-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1SC1=CC(F)=CC(F)=C1 ROCYHXLINRXWJW-UHFFFAOYSA-N 0.000 description 1
- NSOLEUGGZJTHNS-UHFFFAOYSA-N 3-(3-fluorophenoxy)-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=CC=CC(F)=C1 NSOLEUGGZJTHNS-UHFFFAOYSA-N 0.000 description 1
- NCQXDPFJWCBCEZ-UHFFFAOYSA-N 3-(4-bromophenoxy)-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=CC=C(Br)C=C1 NCQXDPFJWCBCEZ-UHFFFAOYSA-N 0.000 description 1
- SSUJSRHMLFBGKA-UHFFFAOYSA-N 3-(4-chlorophenoxy)-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=CC=C(Cl)C=C1 SSUJSRHMLFBGKA-UHFFFAOYSA-N 0.000 description 1
- MTPQCSUYJXVPPH-UHFFFAOYSA-N 3-(4-fluorophenoxy)-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=CC=C(F)C=C1 MTPQCSUYJXVPPH-UHFFFAOYSA-N 0.000 description 1
- VUGRBAACKWNRRJ-UHFFFAOYSA-N 3-(4-fluorophenyl)sulfanyl-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1SC1=CC=C(F)C=C1 VUGRBAACKWNRRJ-UHFFFAOYSA-N 0.000 description 1
- HFLBVHGFPPEJBA-UHFFFAOYSA-N 3-(4-methylsulfonylphenyl)-2-phenoxycyclopent-2-en-1-one Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C(CCC1=O)=C1OC1=CC=CC=C1 HFLBVHGFPPEJBA-UHFFFAOYSA-N 0.000 description 1
- RFJSWOCVCRPHJX-UHFFFAOYSA-N 3-(4-methylsulfonylphenyl)-4-phenylsulfanyl-2h-furan-5-one Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C(COC1=O)=C1SC1=CC=CC=C1 RFJSWOCVCRPHJX-UHFFFAOYSA-N 0.000 description 1
- XCNHDBDVIVAJHX-UHFFFAOYSA-N 3-(5-bromopyridin-2-yl)oxy-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=CC=C(Br)C=N1 XCNHDBDVIVAJHX-UHFFFAOYSA-N 0.000 description 1
- VRNJUSJNNZDCAE-UHFFFAOYSA-N 3-(5-chloropyridin-2-yl)oxy-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=CC=C(Cl)C=N1 VRNJUSJNNZDCAE-UHFFFAOYSA-N 0.000 description 1
- FQHQBFIVQROQKA-UHFFFAOYSA-N 3-(6-aminopyridin-2-yl)oxy-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=CC=CC(N)=N1 FQHQBFIVQROQKA-UHFFFAOYSA-N 0.000 description 1
- FZIZEPNKLINHJQ-UHFFFAOYSA-N 3-(6-chloropyridin-2-yl)oxy-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=CC=CC(Cl)=N1 FZIZEPNKLINHJQ-UHFFFAOYSA-N 0.000 description 1
- HSNXDRXMMFAZGU-UHFFFAOYSA-N 3-(6-chloropyridin-3-yl)oxy-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=CC=C(Cl)N=C1 HSNXDRXMMFAZGU-UHFFFAOYSA-N 0.000 description 1
- AFFHKECMMQJKLB-UHFFFAOYSA-N 3-(diethylamino)-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound CC1(C)OC(=O)C(N(CC)CC)=C1C1=CC=C(S(C)(=O)=O)C=C1 AFFHKECMMQJKLB-UHFFFAOYSA-N 0.000 description 1
- IUPMBEGMKVHDEZ-UHFFFAOYSA-N 3-[(3,4-difluorophenyl)-hydroxymethyl]-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1C(O)C1=CC=C(F)C(F)=C1 IUPMBEGMKVHDEZ-UHFFFAOYSA-N 0.000 description 1
- WUWDLXZGHZSWQZ-UHFFFAOYSA-N 3-[(3,5-dimethyl-1H-pyrrol-2-yl)methylidene]-1H-indol-2-one Chemical compound N1C(C)=CC(C)=C1C=C1C2=CC=CC=C2NC1=O WUWDLXZGHZSWQZ-UHFFFAOYSA-N 0.000 description 1
- CMXGNFNTQWOTRG-UHFFFAOYSA-N 3-[(4-fluorophenyl)methyl]-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1CC1=CC=C(F)C=C1 CMXGNFNTQWOTRG-UHFFFAOYSA-N 0.000 description 1
- NHFDRBXTEDBWCZ-ZROIWOOFSA-N 3-[2,4-dimethyl-5-[(z)-(2-oxo-1h-indol-3-ylidene)methyl]-1h-pyrrol-3-yl]propanoic acid Chemical compound OC(=O)CCC1=C(C)NC(\C=C/2C3=CC=CC=C3NC\2=O)=C1C NHFDRBXTEDBWCZ-ZROIWOOFSA-N 0.000 description 1
- BWWGQVVECVBFOE-UHFFFAOYSA-N 3-anilino-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1NC1=CC=CC=C1 BWWGQVVECVBFOE-UHFFFAOYSA-N 0.000 description 1
- SBPBUYQZVFIIBK-UHFFFAOYSA-N 3-benzoyl-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1C(=O)C1=CC=CC=C1 SBPBUYQZVFIIBK-UHFFFAOYSA-N 0.000 description 1
- KNHHNILXEQGEIW-UHFFFAOYSA-N 3-benzyl-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1CC1=CC=CC=C1 KNHHNILXEQGEIW-UHFFFAOYSA-N 0.000 description 1
- CURYRIVJTBNEGU-UHFFFAOYSA-L 3-bromo-1-[12-(3-bromopropanoyl)-3,12-diaza-6,9-diazoniadispiro[5.2.5^{9}.2^{6}]hexadecan-3-yl]propan-1-one;dichloride Chemical compound [Cl-].[Cl-].C1CN(C(=O)CCBr)CC[N+]21CC[N+]1(CCN(CC1)C(=O)CCBr)CC2 CURYRIVJTBNEGU-UHFFFAOYSA-L 0.000 description 1
- BIXWNJAOOLPDOM-UHFFFAOYSA-N 3-butan-2-yloxy-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound CC1(C)OC(=O)C(OC(C)CC)=C1C1=CC=C(S(C)(=O)=O)C=C1 BIXWNJAOOLPDOM-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- XJWSIWJICISLID-UHFFFAOYSA-N 3-cyclohexyloxy-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1CCCCC1 XJWSIWJICISLID-UHFFFAOYSA-N 0.000 description 1
- QCQWGGMDTWVKQQ-UHFFFAOYSA-N 3-cyclopentyloxy-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1CCCC1 QCQWGGMDTWVKQQ-UHFFFAOYSA-N 0.000 description 1
- QCJZLPOAJAGFAN-UHFFFAOYSA-N 3-isoquinolin-3-yloxy-5,5-dimethyl-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound CC1(C)OC(=O)C(OC=2N=CC3=CC=CC=C3C=2)=C1C1=CC=C(S(C)(=O)=O)C=C1 QCJZLPOAJAGFAN-UHFFFAOYSA-N 0.000 description 1
- VTFGJEYZCUWSAM-UHFFFAOYSA-N 3-methoxy-5-(trifluoromethyl)aniline Chemical compound COC1=CC(N)=CC(C(F)(F)F)=C1 VTFGJEYZCUWSAM-UHFFFAOYSA-N 0.000 description 1
- ZETIVVHRRQLWFW-UHFFFAOYSA-N 3-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC(C=O)=C1 ZETIVVHRRQLWFW-UHFFFAOYSA-N 0.000 description 1
- WEQPBCSPRXFQQS-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazole Chemical compound C1CC=NO1 WEQPBCSPRXFQQS-UHFFFAOYSA-N 0.000 description 1
- WIYNWLBOSGNXEH-UHFFFAOYSA-N 4-(2-amino-6,7-dimethoxyquinazolin-4-yl)phenol Chemical compound C=12C=C(OC)C(OC)=CC2=NC(N)=NC=1C1=CC=C(O)C=C1 WIYNWLBOSGNXEH-UHFFFAOYSA-N 0.000 description 1
- RRRQRRASTZHHRI-UHFFFAOYSA-N 4-(2-phenylimidazol-1-yl)-n-pyridin-2-ylpyrimidin-2-amine Chemical compound N=1C=CC(N2C(=NC=C2)C=2C=CC=CC=2)=NC=1NC1=CC=CC=N1 RRRQRRASTZHHRI-UHFFFAOYSA-N 0.000 description 1
- ZGXGYHUSQXJPID-UHFFFAOYSA-N 4-(3,4-dichlorophenyl)-3-(4-methylsulfonylphenyl)-2h-furan-5-one Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=C(Cl)C(Cl)=CC=2)C(=O)OC1 ZGXGYHUSQXJPID-UHFFFAOYSA-N 0.000 description 1
- INRQTVDUZFESAO-UHFFFAOYSA-N 4-(3,4-difluorophenyl)-3-(4-methylsulfonylphenyl)-2h-furan-5-one Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=C(F)C(F)=CC=2)C(=O)OC1 INRQTVDUZFESAO-UHFFFAOYSA-N 0.000 description 1
- KZNGNTKISMAXAG-UHFFFAOYSA-N 4-(3-fluorophenyl)-3-(4-methylsulfonylphenyl)-2h-furan-5-one Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=C(F)C=CC=2)C(=O)OC1 KZNGNTKISMAXAG-UHFFFAOYSA-N 0.000 description 1
- DDTCKPDYMNJNGL-UHFFFAOYSA-N 4-(4-methylsulfonylphenyl)-3-phenoxy-1-oxaspiro[4.4]non-3-en-2-one Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C(C1(CCCC1)OC1=O)=C1OC1=CC=CC=C1 DDTCKPDYMNJNGL-UHFFFAOYSA-N 0.000 description 1
- GGPKVHLOTGDVJV-UHFFFAOYSA-N 4-(4-methylsulfonylphenyl)-3-phenylsulfanyl-1-oxaspiro[4.4]non-3-en-2-one Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C(C1(CCCC1)OC1=O)=C1SC1=CC=CC=C1 GGPKVHLOTGDVJV-UHFFFAOYSA-N 0.000 description 1
- MQGIBKPZEILKCA-UHFFFAOYSA-N 4-(5-isoquinolin-1-yloxy-3,3-dimethyl-4-methylsulfonylcyclohexa-1,5-dien-1-yl)-2h-furan-5-one Chemical compound C1=C(OC=2C3=CC=CC=C3C=CN=2)C(S(C)(=O)=O)C(C)(C)C=C1C1=CCOC1=O MQGIBKPZEILKCA-UHFFFAOYSA-N 0.000 description 1
- OZBUFFXESDBEHG-FXILSDISSA-N 4-[[(2e,4e,6e,8e)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenoyl]amino]benzoic acid Chemical compound C=1C=C(C(O)=O)C=CC=1NC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OZBUFFXESDBEHG-FXILSDISSA-N 0.000 description 1
- NPKDCCRVSJRVIZ-UHFFFAOYSA-N 4-[[5-[[4-[(3-chlorophenyl)methyl]-4-(hydroxymethyl)piperidin-1-yl]methyl]-2-methylimidazol-1-yl]methyl]benzonitrile Chemical compound C=1C=C(C#N)C=CC=1CN1C(C)=NC=C1CN(CC1)CCC1(CO)CC1=CC=CC(Cl)=C1 NPKDCCRVSJRVIZ-UHFFFAOYSA-N 0.000 description 1
- OAIUDXOPIYIFPT-UHFFFAOYSA-N 4-[[5-[[4-[(4-chloropyridin-2-yl)methyl]-4-(hydroxymethyl)piperidin-1-yl]methyl]-2-methylimidazol-1-yl]methyl]benzonitrile Chemical compound C=1C=C(C#N)C=CC=1CN1C(C)=NC=C1CN(CC1)CCC1(CO)CC1=CC(Cl)=CC=N1 OAIUDXOPIYIFPT-UHFFFAOYSA-N 0.000 description 1
- GFFXZLZWLOBBLO-BWVDBABLSA-N 4-amino-1-[(2r,4s,5r)-3-(fluoromethylidene)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound O=C1N=C(N)C=CN1[C@H]1C(=CF)[C@H](O)[C@@H](CO)O1 GFFXZLZWLOBBLO-BWVDBABLSA-N 0.000 description 1
- PULHLIOPJXPGJN-BWVDBABLSA-N 4-amino-1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)-3-methylideneoxolan-2-yl]pyrimidin-2-one Chemical compound O=C1N=C(N)C=CN1[C@H]1C(=C)[C@H](O)[C@@H](CO)O1 PULHLIOPJXPGJN-BWVDBABLSA-N 0.000 description 1
- 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 1
- DFOHHQRGDOQMKG-UHFFFAOYSA-N 4-chloro-2-methylsulfanylpyrimidine Chemical compound CSC1=NC=CC(Cl)=N1 DFOHHQRGDOQMKG-UHFFFAOYSA-N 0.000 description 1
- NIOSQWXWKIKKEH-UHFFFAOYSA-N 4-chloro-n-(3,5-dimethylphenyl)pyrimidin-2-amine Chemical compound CC1=CC(C)=CC(NC=2N=C(Cl)C=CN=2)=C1 NIOSQWXWKIKKEH-UHFFFAOYSA-N 0.000 description 1
- PBZHVTZQMBGKMT-UHFFFAOYSA-N 4-phenyl-2h-furan-5-one Chemical compound O=C1OCC=C1C1=CC=CC=C1 PBZHVTZQMBGKMT-UHFFFAOYSA-N 0.000 description 1
- HIUVVOXSYZYIBH-UHFFFAOYSA-N 5,5-dimethyl-3-(2-methylpropoxy)-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound CC1(C)OC(=O)C(OCC(C)C)=C1C1=CC=C(S(C)(=O)=O)C=C1 HIUVVOXSYZYIBH-UHFFFAOYSA-N 0.000 description 1
- QZBCQQRCXKYILS-UHFFFAOYSA-N 5,5-dimethyl-3-(6-methylpyridin-2-yl)oxy-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound CC1=CC=CC(OC=2C(OC(C)(C)C=2C=2C=CC(=CC=2)S(C)(=O)=O)=O)=N1 QZBCQQRCXKYILS-UHFFFAOYSA-N 0.000 description 1
- HJZXSUAVCFVGNB-UHFFFAOYSA-N 5,5-dimethyl-3-(6-methylpyridin-3-yl)oxy-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C1=NC(C)=CC=C1OC(C(OC1(C)C)=O)=C1C1=CC=C(S(C)(=O)=O)C=C1 HJZXSUAVCFVGNB-UHFFFAOYSA-N 0.000 description 1
- RJSHDZXWIHIJBI-UHFFFAOYSA-N 5,5-dimethyl-3-(n-methylanilino)-4-(4-methylsulfonylphenyl)furan-2-one Chemical compound C=1C=CC=CC=1N(C)C(C(OC1(C)C)=O)=C1C1=CC=C(S(C)(=O)=O)C=C1 RJSHDZXWIHIJBI-UHFFFAOYSA-N 0.000 description 1
- YMECDTRUPBWAKF-UHFFFAOYSA-N 5,5-dimethyl-4-(4-methylsulfonylphenyl)-3-(1,3-thiazol-2-ylsulfanyl)furan-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1SC1=NC=CS1 YMECDTRUPBWAKF-UHFFFAOYSA-N 0.000 description 1
- LFRQDTGNFOZLCA-UHFFFAOYSA-N 5,5-dimethyl-4-(4-methylsulfonylphenyl)-3-pentan-3-yloxyfuran-2-one Chemical compound CC1(C)OC(=O)C(OC(CC)CC)=C1C1=CC=C(S(C)(=O)=O)C=C1 LFRQDTGNFOZLCA-UHFFFAOYSA-N 0.000 description 1
- OEUFTIBZEDUUCK-UHFFFAOYSA-N 5,5-dimethyl-4-(4-methylsulfonylphenyl)-3-phenoxyfuran-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=CC=CC=C1 OEUFTIBZEDUUCK-UHFFFAOYSA-N 0.000 description 1
- KFKIOJSNPDLTTQ-UHFFFAOYSA-N 5,5-dimethyl-4-(4-methylsulfonylphenyl)-3-phenylsulfanylfuran-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1SC1=CC=CC=C1 KFKIOJSNPDLTTQ-UHFFFAOYSA-N 0.000 description 1
- BXKQWMSQWNZDTH-UHFFFAOYSA-N 5,5-dimethyl-4-(4-methylsulfonylphenyl)-3-pyridin-2-yloxyfuran-2-one Chemical compound C=1C=C(S(C)(=O)=O)C=CC=1C=1C(C)(C)OC(=O)C=1OC1=CC=CC=N1 BXKQWMSQWNZDTH-UHFFFAOYSA-N 0.000 description 1
- HEUMSYRGLQWJQL-UHFFFAOYSA-N 5,5-dimethyl-4-(4-methylsulfonylphenyl)-3-quinazolin-4-yloxyfuran-2-one Chemical compound CC1(C)OC(=O)C(OC=2C3=CC=CC=C3N=CN=2)=C1C1=CC=C(S(C)(=O)=O)C=C1 HEUMSYRGLQWJQL-UHFFFAOYSA-N 0.000 description 1
- BKAIDULGUXNMAB-UHFFFAOYSA-N 5,5-dimethyl-4-(4-methylsulfonylphenyl)-3-quinolin-2-yloxyfuran-2-one Chemical compound CC1(C)OC(=O)C(OC=2N=C3C=CC=CC3=CC=2)=C1C1=CC=C(S(C)(=O)=O)C=C1 BKAIDULGUXNMAB-UHFFFAOYSA-N 0.000 description 1
- MGPCJDUYMCTDRP-UHFFFAOYSA-N 5,5-dimethyl-4-(4-methylsulfonylphenyl)-3-quinolin-6-yloxyfuran-2-one Chemical compound CC1(C)OC(=O)C(OC=2C=C3C=CC=NC3=CC=2)=C1C1=CC=C(S(C)(=O)=O)C=C1 MGPCJDUYMCTDRP-UHFFFAOYSA-N 0.000 description 1
- YKQWFRUYFSDCKK-UHFFFAOYSA-N 5-(1h-imidazol-2-yl)pyrimidine Chemical compound C1=CNC(C=2C=NC=NC=2)=N1 YKQWFRUYFSDCKK-UHFFFAOYSA-N 0.000 description 1
- LGZKGOGODCLQHG-CYBMUJFWSA-N 5-[(2r)-2-hydroxy-2-(3,4,5-trimethoxyphenyl)ethyl]-2-methoxyphenol Chemical compound C1=C(O)C(OC)=CC=C1C[C@@H](O)C1=CC(OC)=C(OC)C(OC)=C1 LGZKGOGODCLQHG-CYBMUJFWSA-N 0.000 description 1
- 239000002677 5-alpha reductase inhibitor Substances 0.000 description 1
- XAUDJQYHKZQPEU-KVQBGUIXSA-N 5-aza-2'-deoxycytidine Chemical compound O=C1N=C(N)N=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 XAUDJQYHKZQPEU-KVQBGUIXSA-N 0.000 description 1
- QWMFKVNJIYNWII-UHFFFAOYSA-N 5-bromo-2-(2,5-dimethylpyrrol-1-yl)pyridine Chemical compound CC1=CC=C(C)N1C1=CC=C(Br)C=N1 QWMFKVNJIYNWII-UHFFFAOYSA-N 0.000 description 1
- PFYCGEZLYBVOOJ-UHFFFAOYSA-N 5-methyl-4-(4-methylsulfonylphenyl)-3-propan-2-yloxy-5-propylfuran-2-one Chemical compound CCCC1(C)OC(=O)C(OC(C)C)=C1C1=CC=C(S(C)(=O)=O)C=C1 PFYCGEZLYBVOOJ-UHFFFAOYSA-N 0.000 description 1
- GBOQUHPYCRYKGV-UHFFFAOYSA-N 5-nitro-2-(2-pyrrolidin-1-ylethyl)benzo[de]isoquinoline-1,3-dione Chemical compound O=C1C(C=23)=CC=CC3=CC([N+](=O)[O-])=CC=2C(=O)N1CCN1CCCC1 GBOQUHPYCRYKGV-UHFFFAOYSA-N 0.000 description 1
- KAEVHZSIYLATMK-UHFFFAOYSA-N 6-n-[bis(aziridin-1-yl)phosphoryl]-2-n,2-n,7-trimethylpurine-2,6-diamine Chemical compound C=12N(C)C=NC2=NC(N(C)C)=NC=1NP(=O)(N1CC1)N1CC1 KAEVHZSIYLATMK-UHFFFAOYSA-N 0.000 description 1
- RGVRUQHYQSORBY-UHFFFAOYSA-N 7-(4-amino-5-hydroxy-6-methyloxan-2-yl)oxy-6,9,11-trihydroxy-9-(2-hydroxyethyl)-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione Chemical compound C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(CCO)CC1OC1CC(N)C(O)C(C)O1 RGVRUQHYQSORBY-UHFFFAOYSA-N 0.000 description 1
- 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 1
- KABRXLINDSPGDF-UHFFFAOYSA-N 7-bromoisoquinoline Chemical compound C1=CN=CC2=CC(Br)=CC=C21 KABRXLINDSPGDF-UHFFFAOYSA-N 0.000 description 1
- SHGAZHPCJJPHSC-ZVCIMWCZSA-N 9-cis-retinoic acid Chemical compound OC(=O)/C=C(\C)/C=C/C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-ZVCIMWCZSA-N 0.000 description 1
- ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 1
- 102100038778 Amphiregulin Human genes 0.000 description 1
- 108010033760 Amphiregulin Proteins 0.000 description 1
- 229940123413 Angiotensin II antagonist Drugs 0.000 description 1
- 108020004491 Antisense DNA Proteins 0.000 description 1
- 108020005544 Antisense RNA Proteins 0.000 description 1
- 239000004475 Arginine Substances 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
- 108010019625 Atazanavir Sulfate Proteins 0.000 description 1
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 102400001242 Betacellulin Human genes 0.000 description 1
- 101800001382 Betacellulin Proteins 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 229940122361 Bisphosphonate Drugs 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 206010048962 Brain oedema Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 108010082830 CEP 2563 Proteins 0.000 description 1
- QAGYKUNXZHXKMR-UHFFFAOYSA-N CPD000469186 Natural products CC1=C(O)C=CC=C1C(=O)NC(C(O)CN1C(CC2CCCCC2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 1
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 description 1
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- AOCCBINRVIKJHY-UHFFFAOYSA-N Carmofur Chemical compound CCCCCCNC(=O)N1C=C(F)C(=O)NC1=O AOCCBINRVIKJHY-UHFFFAOYSA-N 0.000 description 1
- FKSNGMRDHNSAAX-UHFFFAOYSA-N Cc1cc(C)cc(Nc2nccc(-[n]3c(C#N)ncc3)n2)c1 Chemical compound Cc1cc(C)cc(Nc2nccc(-[n]3c(C#N)ncc3)n2)c1 FKSNGMRDHNSAAX-UHFFFAOYSA-N 0.000 description 1
- ZEOWTGPWHLSLOG-UHFFFAOYSA-N Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F Chemical compound Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F ZEOWTGPWHLSLOG-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 229930188224 Cryptophycin Natural products 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 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
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- DYHSDKLCOJIUFX-UHFFFAOYSA-N Di-tert-butyl dicarbonate Substances CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
- LQKSHSFQQRCAFW-UHFFFAOYSA-N Dolastatin 15 Natural products COC1=CC(=O)N(C(=O)C(OC(=O)C2N(CCC2)C(=O)C2N(CCC2)C(=O)C(C(C)C)N(C)C(=O)C(NC(=O)C(C(C)C)N(C)C)C(C)C)C(C)C)C1CC1=CC=CC=C1 LQKSHSFQQRCAFW-UHFFFAOYSA-N 0.000 description 1
- ZQZFYGIXNQKOAV-OCEACIFDSA-N Droloxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=C(O)C=CC=1)\C1=CC=C(OCCN(C)C)C=C1 ZQZFYGIXNQKOAV-OCEACIFDSA-N 0.000 description 1
- XPOQHMRABVBWPR-UHFFFAOYSA-N Efavirenz Natural products O1C(=O)NC2=CC=C(Cl)C=C2C1(C(F)(F)F)C#CC1CC1 XPOQHMRABVBWPR-UHFFFAOYSA-N 0.000 description 1
- SAMRUMKYXPVKPA-VFKOLLTISA-N Enocitabine Chemical compound O=C1N=C(NC(=O)CCCCCCCCCCCCCCCCCCCCC)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 SAMRUMKYXPVKPA-VFKOLLTISA-N 0.000 description 1
- 108010056764 Eptifibatide Proteins 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 206010015866 Extravasation Diseases 0.000 description 1
- RSCIYYHIBVZXDI-UHFFFAOYSA-O Fagaridine Chemical compound C1=C2OCOC2=CC2=CC=C3C4=CC=C(OC)C(O)=C4C=[N+](C)C3=C21 RSCIYYHIBVZXDI-UHFFFAOYSA-O 0.000 description 1
- 108010012088 Fibrinogen Receptors Proteins 0.000 description 1
- 102100023593 Fibroblast growth factor receptor 1 Human genes 0.000 description 1
- 101710182386 Fibroblast growth factor receptor 1 Proteins 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- VWUXBMIQPBEWFH-WCCTWKNTSA-N Fulvestrant Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3[C@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)CC2=C1 VWUXBMIQPBEWFH-WCCTWKNTSA-N 0.000 description 1
- CEVCTNCUIVEQOY-UHFFFAOYSA-N Fumagillol Natural products O1C(CC=C(C)C)C1(C)C1C(OC)C(O)CCC21CO2 CEVCTNCUIVEQOY-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 101150066516 GST gene Proteins 0.000 description 1
- 101710113436 GTPase KRas Proteins 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
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 101800001649 Heparin-binding EGF-like growth factor Proteins 0.000 description 1
- 102400001369 Heparin-binding EGF-like growth factor Human genes 0.000 description 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- 101000808011 Homo sapiens Vascular endothelial growth factor A Proteins 0.000 description 1
- 101000851018 Homo sapiens Vascular endothelial growth factor receptor 1 Proteins 0.000 description 1
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin 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=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 1
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 1
- JJKOTMDDZAJTGQ-DQSJHHFOSA-N Idoxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN2CCCC2)=CC=1)/C1=CC=C(I)C=C1 JJKOTMDDZAJTGQ-DQSJHHFOSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102100023915 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- SHGAZHPCJJPHSC-NUEINMDLSA-N Isotretinoin Chemical compound OC(=O)C=C(C)/C=C/C=C(C)C=CC1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-NUEINMDLSA-N 0.000 description 1
- KJHKTHWMRKYKJE-SUGCFTRWSA-N Kaletra Chemical compound N1([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=2C=CC=CC=2)NC(=O)COC=2C(=CC=CC=2C)C)CC=2C=CC=CC=2)CCCNC1=O KJHKTHWMRKYKJE-SUGCFTRWSA-N 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- MLFKVJCWGUZWNV-UHFFFAOYSA-N L-alanosine Natural products OC(=O)C(N)CN(O)N=O MLFKVJCWGUZWNV-UHFFFAOYSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 108010043135 L-methionine gamma-lyase Proteins 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- PONPPNYZKHNPKZ-UHFFFAOYSA-N Lambdamycin Natural products OC1C(OC)C(O)C(C)OC1OC1C(O)C(O)C(C)OC1OC1=CC=CC2=C(O)C(C(O3)=O)=C4C5=C3C=CC(C)=C5C(=O)OC4=C12 PONPPNYZKHNPKZ-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 206010027259 Meningitis tuberculous Diseases 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- 108010006035 Metalloproteases Proteins 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101100372766 Mus musculus Kdr gene Proteins 0.000 description 1
- 101100268066 Mus musculus Zap70 gene Proteins 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- 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
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 229910020700 Na3VO4 Inorganic materials 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 102400000058 Neuregulin-1 Human genes 0.000 description 1
- 108090000556 Neuregulin-1 Proteins 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 208000005072 Oncogenic osteomalacia Diseases 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 241000906034 Orthops Species 0.000 description 1
- 208000010191 Osteitis Deformans Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 208000027868 Paget disease Diseases 0.000 description 1
- KMSKQZKKOZQFFG-HSUXVGOQSA-N Pirarubicin Chemical compound O([C@H]1[C@@H](N)C[C@@H](O[C@H]1C)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]1CCCCO1 KMSKQZKKOZQFFG-HSUXVGOQSA-N 0.000 description 1
- 102000001393 Platelet-Derived Growth Factor alpha Receptor Human genes 0.000 description 1
- 108010068588 Platelet-Derived Growth Factor alpha Receptor Proteins 0.000 description 1
- 108010020346 Polyglutamic Acid Proteins 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- HRHKSTOGXBBQCB-UHFFFAOYSA-N Porfiromycine Chemical compound O=C1C(N)=C(C)C(=O)C2=C1C(COC(N)=O)C1(OC)C3N(C)C3CN12 HRHKSTOGXBBQCB-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
- HFVNWDWLWUCIHC-GUPDPFMOSA-N Prednimustine Chemical compound O=C([C@@]1(O)CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)[C@@H](O)C[C@@]21C)COC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 HFVNWDWLWUCIHC-GUPDPFMOSA-N 0.000 description 1
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 1
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 1
- AHHFEZNOXOZZQA-ZEBDFXRSSA-N Ranimustine Chemical compound CO[C@H]1O[C@H](CNC(=O)N(CCCl)N=O)[C@@H](O)[C@H](O)[C@H]1O AHHFEZNOXOZZQA-ZEBDFXRSSA-N 0.000 description 1
- 108091005682 Receptor kinases Proteins 0.000 description 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 1
- 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 1
- 102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 description 1
- 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- OWPCHSCAPHNHAV-UHFFFAOYSA-N Rhizoxin Natural products C1C(O)C2(C)OC2C=CC(C)C(OC(=O)C2)CC2CC2OC2C(=O)OC1C(C)C(OC)C(C)=CC=CC(C)=CC1=COC(C)=N1 OWPCHSCAPHNHAV-UHFFFAOYSA-N 0.000 description 1
- IIDJRNMFWXDHID-UHFFFAOYSA-N Risedronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=CC=CN=C1 IIDJRNMFWXDHID-UHFFFAOYSA-N 0.000 description 1
- NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- WBNUCLPUOSXSNJ-ZDUSSCGKSA-N Sibrafiban Chemical compound C1CC(OCC(=O)OCC)CCN1C(=O)[C@H](C)NC(=O)C1=CC=C(C(=N)NO)C=C1 WBNUCLPUOSXSNJ-ZDUSSCGKSA-N 0.000 description 1
- OCOKWVBYZHBHLU-UHFFFAOYSA-N Sobuzoxane Chemical compound C1C(=O)N(COC(=O)OCC(C)C)C(=O)CN1CCN1CC(=O)N(COC(=O)OCC(C)C)C(=O)C1 OCOKWVBYZHBHLU-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 241000256251 Spodoptera frugiperda Species 0.000 description 1
- 229920002253 Tannate Polymers 0.000 description 1
- NAVMQTYZDKMPEU-UHFFFAOYSA-N Targretin Chemical compound CC1=CC(C(CCC2(C)C)(C)C)=C2C=C1C(=C)C1=CC=C(C(O)=O)C=C1 NAVMQTYZDKMPEU-UHFFFAOYSA-N 0.000 description 1
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- SUJUHGSWHZTSEU-UHFFFAOYSA-N Tipranavir Natural products C1C(O)=C(C(CC)C=2C=C(NS(=O)(=O)C=3N=CC(=CC=3)C(F)(F)F)C=CC=2)C(=O)OC1(CCC)CCC1=CC=CC=C1 SUJUHGSWHZTSEU-UHFFFAOYSA-N 0.000 description 1
- IVTVGDXNLFLDRM-HNNXBMFYSA-N Tomudex Chemical compound C=1C=C2NC(C)=NC(=O)C2=CC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)S1 IVTVGDXNLFLDRM-HNNXBMFYSA-N 0.000 description 1
- 101800004564 Transforming growth factor alpha Proteins 0.000 description 1
- 102400001320 Transforming growth factor alpha Human genes 0.000 description 1
- 208000022971 Tuberculous meningitis Diseases 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 1
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 1
- XMYKNCNAZKMVQN-NYYWCZLTSA-N [(e)-(3-aminopyridin-2-yl)methylideneamino]thiourea Chemical compound NC(=S)N\N=C\C1=NC=CC=C1N XMYKNCNAZKMVQN-NYYWCZLTSA-N 0.000 description 1
- XSMVECZRZBFTIZ-UHFFFAOYSA-M [2-(aminomethyl)cyclobutyl]methanamine;2-oxidopropanoate;platinum(4+) Chemical compound [Pt+4].CC([O-])C([O-])=O.NCC1CCC1CN XSMVECZRZBFTIZ-UHFFFAOYSA-M 0.000 description 1
- CKXIPXAIFMTQCS-LRDUUELOSA-N [2-[(2s,4s)-4-[(2r,3r,4r,5s,6s)-3-fluoro-4,5-dihydroxy-6-methyloxan-2-yl]oxy-2,5,12-trihydroxy-7-methoxy-6,11-dioxo-3,4-dihydro-1h-tetracen-2-yl]-2-oxoethyl] 3-aminopropanoate 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)COC(=O)CCN)[C@@H]1O[C@@H](C)[C@@H](O)[C@@H](O)[C@H]1F CKXIPXAIFMTQCS-LRDUUELOSA-N 0.000 description 1
- AGJKPCQIEBYZHZ-UHFFFAOYSA-N [3-[(4-acetylpiperazin-1-yl)methyl]-5-methylphenyl]carbamic acid Chemical compound C1CN(C(=O)C)CCN1CC1=CC(C)=CC(NC(O)=O)=C1 AGJKPCQIEBYZHZ-UHFFFAOYSA-N 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- DJSLOQFVVUBAKG-UHFFFAOYSA-N [4-(3-chloroanilino)-5,6-dimethyl-7H-pyrrolo[2,3-d]pyrimidin-2-yl]methanesulfonic acid Chemical compound C=12C(C)=C(C)NC2=NC(CS(O)(=O)=O)=NC=1NC1=CC=CC(Cl)=C1 DJSLOQFVVUBAKG-UHFFFAOYSA-N 0.000 description 1
- MCGSCOLBFJQGHM-SCZZXKLOSA-N abacavir Chemical compound C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1 MCGSCOLBFJQGHM-SCZZXKLOSA-N 0.000 description 1
- 229960004748 abacavir Drugs 0.000 description 1
- 229960000446 abciximab Drugs 0.000 description 1
- UVIQSJCZCSLXRZ-UBUQANBQSA-N abiraterone acetate Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CC[C@@H](CC4=CC[C@H]31)OC(=O)C)C=C2C1=CC=CN=C1 UVIQSJCZCSLXRZ-UBUQANBQSA-N 0.000 description 1
- 229960004103 abiraterone acetate Drugs 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 229950005033 alanosine Drugs 0.000 description 1
- 229940062527 alendronate Drugs 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229960001445 alitretinoin Drugs 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 229960000473 altretamine Drugs 0.000 description 1
- 229940037003 alum Drugs 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 229960003896 aminopterin Drugs 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 229960001830 amprenavir Drugs 0.000 description 1
- YMARZQAQMVYCKC-OEMFJLHTSA-N amprenavir Chemical compound C([C@@H]([C@H](O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1COCC1)C1=CC=CC=C1 YMARZQAQMVYCKC-OEMFJLHTSA-N 0.000 description 1
- 229960002550 amrubicin Drugs 0.000 description 1
- VJZITPJGSQKZMX-XDPRQOKASA-N amrubicin Chemical compound O([C@H]1C[C@](CC2=C(O)C=3C(=O)C4=CC=CC=C4C(=O)C=3C(O)=C21)(N)C(=O)C)[C@H]1C[C@H](O)[C@H](O)CO1 VJZITPJGSQKZMX-XDPRQOKASA-N 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 229940030486 androgens Drugs 0.000 description 1
- 239000002870 angiogenesis inducing agent Substances 0.000 description 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 1
- 229950001104 anhydrovinblastine Drugs 0.000 description 1
- CIDNKDMVSINJCG-GKXONYSUSA-N annamycin Chemical compound I[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(=O)CO)C1 CIDNKDMVSINJCG-GKXONYSUSA-N 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 230000003527 anti-angiogenesis Effects 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 230000000123 anti-resoprtive effect Effects 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 239000003816 antisense DNA Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- GOLCXWYRSKYTSP-UHFFFAOYSA-N arsenic trioxide Inorganic materials O1[As]2O[As]1O2 GOLCXWYRSKYTSP-UHFFFAOYSA-N 0.000 description 1
- MCGDSOGUHLTADD-UHFFFAOYSA-N arzoxifene Chemical compound C1=CC(OC)=CC=C1C1=C(OC=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 MCGDSOGUHLTADD-UHFFFAOYSA-N 0.000 description 1
- TWHSQQYCDVSBRK-UHFFFAOYSA-N asulacrine Chemical compound C12=CC=CC(C)=C2N=C2C(C(=O)NC)=CC=CC2=C1NC1=CC=C(NS(C)(=O)=O)C=C1OC TWHSQQYCDVSBRK-UHFFFAOYSA-N 0.000 description 1
- 229950011088 asulacrine Drugs 0.000 description 1
- AXRYRYVKAWYZBR-GASGPIRDSA-N atazanavir Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)[C@@H](O)CN(CC=1C=CC(=CC=1)C=1N=CC=CC=1)NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)C1=CC=CC=C1 AXRYRYVKAWYZBR-GASGPIRDSA-N 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 229960005370 atorvastatin Drugs 0.000 description 1
- SHZPNDRIDUBNMH-NIJVSVLQSA-L atorvastatin calcium trihydrate Chemical compound O.O.O.[Ca+2].C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1.C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 SHZPNDRIDUBNMH-NIJVSVLQSA-L 0.000 description 1
- 108010044540 auristatin Proteins 0.000 description 1
- 230000003305 autocrine Effects 0.000 description 1
- KLNFSAOEKUDMFA-UHFFFAOYSA-N azanide;2-hydroxyacetic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OCC(O)=O KLNFSAOEKUDMFA-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- WZPBZJONDBGPKJ-VEHQQRBSSA-N aztreonam Chemical compound O=C1N(S([O-])(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(=N/OC(C)(C)C(O)=O)\C1=CSC([NH3+])=N1 WZPBZJONDBGPKJ-VEHQQRBSSA-N 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- UPABQMWFWCMOFV-UHFFFAOYSA-N benethamine Chemical compound C=1C=CC=CC=1CNCCC1=CC=CC=C1 UPABQMWFWCMOFV-UHFFFAOYSA-N 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
- 229940077388 benzenesulfonate Drugs 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
- 125000005605 benzo group Chemical group 0.000 description 1
- 125000004601 benzofurazanyl group Chemical group N1=C2C(=NO1)C(=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- 229960002938 bexarotene Drugs 0.000 description 1
- 229960000997 bicalutamide Drugs 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 229950008548 bisantrene Drugs 0.000 description 1
- 150000004663 bisphosphonates Chemical class 0.000 description 1
- UBJAHGAUPNGZFF-XOVTVWCYSA-N bms-184476 Chemical compound O([C@H]1[C@@H]2[C@]3(OC(C)=O)CO[C@@H]3C[C@@H]([C@]2(C(=O)[C@H](OC(C)=O)C2=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)C=3C=CC=CC=3)C=3C=CC=CC=3)C[C@]1(O)C2(C)C)C)OCSC)C(=O)C1=CC=CC=C1 UBJAHGAUPNGZFF-XOVTVWCYSA-N 0.000 description 1
- GMJWGJSDPOAZTP-MIDYMNAOSA-N bms-188797 Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](OC(C)=O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)C=4C=CC=CC=4)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)OC)C(=O)C1=CC=CC=C1 GMJWGJSDPOAZTP-MIDYMNAOSA-N 0.000 description 1
- 208000006752 brain edema Diseases 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 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
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 1
- 229940127093 camptothecin Drugs 0.000 description 1
- 229960004117 capecitabine Drugs 0.000 description 1
- 210000001043 capillary endothelial cell Anatomy 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 125000004623 carbolinyl group Chemical group 0.000 description 1
- 150000001722 carbon compounds Chemical class 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 229960003261 carmofur Drugs 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 229960000590 celecoxib Drugs 0.000 description 1
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 108091092356 cellular DNA Proteins 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 108010046713 cemadotin Proteins 0.000 description 1
- 229950009017 cemadotin Drugs 0.000 description 1
- GPUADMRJQVPIAS-QCVDVZFFSA-M cerivastatin sodium Chemical compound [Na+].COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 GPUADMRJQVPIAS-QCVDVZFFSA-M 0.000 description 1
- MXJSQPACGKUSQB-UHFFFAOYSA-N chartreusin Natural products COC1C(O)C(C)OC(OC2C(O)C(O)C(C)OC2Oc3cccc4c(O)c5C(=O)Oc6ccc(C)c7C(=O)Cc(c5c67)c34)C1O MXJSQPACGKUSQB-UHFFFAOYSA-N 0.000 description 1
- YOQPCWIXYUNEET-UHFFFAOYSA-N chembl307697 Chemical compound C1=CC(O)=CC=C1C(C=1C=CC(O)=CC=1)=NNC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O YOQPCWIXYUNEET-UHFFFAOYSA-N 0.000 description 1
- ROWSTIYZUWEOMM-UHFFFAOYSA-N chembl488755 Chemical compound C12=CC=CC=C2C(=O)C2=C1C1=CC=C(O)C=C1N=C2NCCN(C)C ROWSTIYZUWEOMM-UHFFFAOYSA-N 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 125000000068 chlorophenyl group Chemical group 0.000 description 1
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
- 229960002023 chloroprocaine Drugs 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- AMLYAMJWYAIXIA-VWNVYAMZSA-N cilengitide Chemical compound N1C(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](C(C)C)N(C)C(=O)[C@H]1CC1=CC=CC=C1 AMLYAMJWYAIXIA-VWNVYAMZSA-N 0.000 description 1
- 229950009003 cilengitide Drugs 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229940090805 clavulanate Drugs 0.000 description 1
- HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- LGZKGOGODCLQHG-UHFFFAOYSA-N combretastatin Natural products C1=C(O)C(OC)=CC=C1CC(O)C1=CC(OC)=C(OC)C(OC)=C1 LGZKGOGODCLQHG-UHFFFAOYSA-N 0.000 description 1
- 239000003184 complementary RNA Substances 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940035811 conjugated estrogen Drugs 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- POADTFBBIXOWFJ-VWLOTQADSA-N cositecan Chemical compound C1=CC=C2C(CC[Si](C)(C)C)=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 POADTFBBIXOWFJ-VWLOTQADSA-N 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 108010006226 cryptophycin Proteins 0.000 description 1
- PSNOPSMXOBPNNV-VVCTWANISA-N cryptophycin 1 Chemical compound C1=C(Cl)C(OC)=CC=C1C[C@@H]1C(=O)NC[C@@H](C)C(=O)O[C@@H](CC(C)C)C(=O)O[C@H]([C@H](C)[C@@H]2[C@H](O2)C=2C=CC=CC=2)C/C=C/C(=O)N1 PSNOPSMXOBPNNV-VVCTWANISA-N 0.000 description 1
- PSNOPSMXOBPNNV-UHFFFAOYSA-N cryptophycin-327 Natural products C1=C(Cl)C(OC)=CC=C1CC1C(=O)NCC(C)C(=O)OC(CC(C)C)C(=O)OC(C(C)C2C(O2)C=2C=CC=CC=2)CC=CC(=O)N1 PSNOPSMXOBPNNV-UHFFFAOYSA-N 0.000 description 1
- 125000002946 cyanobenzyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 229950006614 cytarabine ocfosfate Drugs 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Natural products NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 229960003603 decitabine Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- WHBIGIKBNXZKFE-UHFFFAOYSA-N delavirdine mesylate Natural products CC(C)NC1=CC=CN=C1N1CCN(C(=O)C=2NC3=CC=C(NS(C)(=O)=O)C=C3C=2)CC1 WHBIGIKBNXZKFE-UHFFFAOYSA-N 0.000 description 1
- 229960000605 dexrazoxane Drugs 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 229950007457 dibrospidium chloride Drugs 0.000 description 1
- ACYGYJFTZSAZKR-UHFFFAOYSA-J dicalcium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Ca+2].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O ACYGYJFTZSAZKR-UHFFFAOYSA-J 0.000 description 1
- AZFLJNIPTRTECV-FUMNGEBKSA-N dienogest Chemical compound C1CC(=O)C=C2CC[C@@H]([C@H]3[C@@](C)([C@](CC3)(O)CC#N)CC3)C3=C21 AZFLJNIPTRTECV-FUMNGEBKSA-N 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229940043237 diethanolamine Drugs 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 description 1
- 125000005436 dihydrobenzothiophenyl group Chemical group S1C(CC2=C1C=CC=C2)* 0.000 description 1
- 125000005435 dihydrobenzoxazolyl group Chemical group O1C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 1
- 125000005047 dihydroimidazolyl group Chemical group N1(CNC=C1)* 0.000 description 1
- 125000001070 dihydroindolyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000005049 dihydrooxadiazolyl group Chemical group O1N(NC=C1)* 0.000 description 1
- 125000005050 dihydrooxazolyl group Chemical group O1C(NC=C1)* 0.000 description 1
- 125000005051 dihydropyrazinyl group Chemical group N1(CC=NC=C1)* 0.000 description 1
- 125000005052 dihydropyrazolyl group Chemical group N1(NCC=C1)* 0.000 description 1
- 125000004655 dihydropyridinyl group Chemical group N1(CC=CC=C1)* 0.000 description 1
- 125000005053 dihydropyrimidinyl group Chemical group N1(CN=CC=C1)* 0.000 description 1
- 125000005054 dihydropyrrolyl group Chemical group [H]C1=C([H])C([H])([H])C([H])([H])N1* 0.000 description 1
- 125000005044 dihydroquinolinyl group Chemical group N1(CC=CC2=CC=CC=C12)* 0.000 description 1
- 125000005056 dihydrothiazolyl group Chemical group S1C(NC=C1)* 0.000 description 1
- 125000005057 dihydrothienyl group Chemical group S1C(CC=C1)* 0.000 description 1
- 125000005058 dihydrotriazolyl group Chemical group N1(NNC=C1)* 0.000 description 1
- 229950009278 dimesna Drugs 0.000 description 1
- SPCNPOWOBZQWJK-UHFFFAOYSA-N dimethoxy-(2-propan-2-ylsulfanylethylsulfanyl)-sulfanylidene-$l^{5}-phosphane Chemical compound COP(=S)(OC)SCCSC(C)C SPCNPOWOBZQWJK-UHFFFAOYSA-N 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- KQYGMURBTJPBPQ-UHFFFAOYSA-L disodium;2-(2-sulfonatoethyldisulfanyl)ethanesulfonate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)CCSSCCS([O-])(=O)=O KQYGMURBTJPBPQ-UHFFFAOYSA-L 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- AMRJKAQTDDKMCE-UHFFFAOYSA-N dolastatin Chemical compound CC(C)C(N(C)C)C(=O)NC(C(C)C)C(=O)N(C)C(C(C)C)C(OC)CC(=O)N1CCCC1C(OC)C(C)C(=O)NC(C=1SC=CN=1)CC1=CC=CC=C1 AMRJKAQTDDKMCE-UHFFFAOYSA-N 0.000 description 1
- 229930188854 dolastatin Natural products 0.000 description 1
- ZWAOHEXOSAUJHY-ZIYNGMLESA-N doxifluridine Chemical compound O[C@@H]1[C@H](O)[C@@H](C)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ZWAOHEXOSAUJHY-ZIYNGMLESA-N 0.000 description 1
- 229950005454 doxifluridine Drugs 0.000 description 1
- 229950004203 droloxifene Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 229940009662 edetate Drugs 0.000 description 1
- 229960003804 efavirenz Drugs 0.000 description 1
- XPOQHMRABVBWPR-ZDUSSCGKSA-N efavirenz Chemical compound C([C@]1(C2=CC(Cl)=CC=C2NC(=O)O1)C(F)(F)F)#CC1CC1 XPOQHMRABVBWPR-ZDUSSCGKSA-N 0.000 description 1
- 229950004438 elinafide Drugs 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 229950005450 emitefur Drugs 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 229950011487 enocitabine Drugs 0.000 description 1
- GLGOPUHVAZCPRB-LROMGURASA-N eptifibatide Chemical compound N1C(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCCCNC(=N)N)NC(=O)CCSSC[C@@H](C(N)=O)NC(=O)[C@@H]2CCCN2C(=O)[C@@H]1CC1=CN=C2[C]1C=CC=C2 GLGOPUHVAZCPRB-LROMGURASA-N 0.000 description 1
- 229960004468 eptifibatide Drugs 0.000 description 1
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 1
- 229950000206 estolate Drugs 0.000 description 1
- 229960001842 estramustine Drugs 0.000 description 1
- FRPJXPJMRWBBIH-RBRWEJTLSA-N estramustine Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 FRPJXPJMRWBBIH-RBRWEJTLSA-N 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- JKKFKPJIXZFSSB-CBZIJGRNSA-N estrone 3-sulfate Chemical compound OS(=O)(=O)OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 JKKFKPJIXZFSSB-CBZIJGRNSA-N 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- LJQKCYFTNDAAPC-UHFFFAOYSA-N ethanol;ethyl acetate Chemical compound CCO.CCOC(C)=O LJQKCYFTNDAAPC-UHFFFAOYSA-N 0.000 description 1
- JEFPWOBULVSOTM-PPHPATTJSA-N ethyl n-[(2s)-5-amino-2-methyl-3-phenyl-1,2-dihydropyrido[3,4-b]pyrazin-7-yl]carbamate;2-hydroxyethanesulfonic acid Chemical compound OCCS(O)(=O)=O.C=1([C@H](C)NC=2C=C(N=C(N)C=2N=1)NC(=O)OCC)C1=CC=CC=C1 JEFPWOBULVSOTM-PPHPATTJSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 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 1
- 229960000752 etoposide phosphate Drugs 0.000 description 1
- 208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 230000036251 extravasation Effects 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000002319 fibrinogen receptor antagonist Substances 0.000 description 1
- DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 description 1
- 229960004039 finasteride Drugs 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 108091071773 flk family Proteins 0.000 description 1
- 229960000390 fludarabine Drugs 0.000 description 1
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 229960002074 flutamide Drugs 0.000 description 1
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
- 229960003765 fluvastatin Drugs 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229960004783 fotemustine Drugs 0.000 description 1
- YAKWPXVTIGTRJH-UHFFFAOYSA-N fotemustine Chemical compound CCOP(=O)(OCC)C(C)NC(=O)N(CCCl)N=O YAKWPXVTIGTRJH-UHFFFAOYSA-N 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 229960002258 fulvestrant Drugs 0.000 description 1
- 229940050411 fumarate Drugs 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 229950011325 galarubicin Drugs 0.000 description 1
- 229950004410 galocitabine Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 1
- 238000003209 gene knockout Methods 0.000 description 1
- 229940045109 genistein Drugs 0.000 description 1
- TZBJGXHYKVUXJN-UHFFFAOYSA-N genistein Natural products C1=CC(O)=CC=C1C1=COC2=CC(O)=CC(O)=C2C1=O TZBJGXHYKVUXJN-UHFFFAOYSA-N 0.000 description 1
- 235000006539 genistein Nutrition 0.000 description 1
- ZCOLJUOHXJRHDI-CMWLGVBASA-N genistein 7-O-beta-D-glucoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 ZCOLJUOHXJRHDI-CMWLGVBASA-N 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 229960001731 gluceptate Drugs 0.000 description 1
- KWMLJOLKUYYJFJ-VFUOTHLCSA-N glucoheptonic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)C(O)=O KWMLJOLKUYYJFJ-VFUOTHLCSA-N 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 229950011595 glufosfamide Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 229940049906 glutamate Drugs 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 125000006277 halobenzyl group Chemical group 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- 125000004634 hexahydroazepinyl group Chemical group N1(CCCCCC1)* 0.000 description 1
- UUVWYPNAQBNQJQ-UHFFFAOYSA-N hexamethylmelamine Chemical compound CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000002657 hormone replacement therapy Methods 0.000 description 1
- 102000055590 human KDR Human genes 0.000 description 1
- 102000058223 human VEGFA Human genes 0.000 description 1
- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N hydroxymaleic acid group Chemical group O/C(/C(=O)O)=C/C(=O)O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- 230000000521 hyperimmunizing effect Effects 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 229960000908 idarubicin Drugs 0.000 description 1
- 229950002248 idoxifene Drugs 0.000 description 1
- 229960001101 ifosfamide Drugs 0.000 description 1
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
- 229960002411 imatinib Drugs 0.000 description 1
- YLMAHDNUQAMNNX-UHFFFAOYSA-N imatinib methanesulfonate Chemical compound CS(O)(=O)=O.C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 YLMAHDNUQAMNNX-UHFFFAOYSA-N 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- DBIGHPPNXATHOF-UHFFFAOYSA-N improsulfan Chemical compound CS(=O)(=O)OCCCNCCCOS(C)(=O)=O DBIGHPPNXATHOF-UHFFFAOYSA-N 0.000 description 1
- 229950008097 improsulfan Drugs 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 229960001936 indinavir Drugs 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- 229950005254 irofulven Drugs 0.000 description 1
- NICJCIQSJJKZAH-AWEZNQCLSA-N irofulven Chemical compound O=C([C@@]1(O)C)C2=CC(C)=C(CO)C2=C(C)C21CC2 NICJCIQSJJKZAH-AWEZNQCLSA-N 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 229960005280 isotretinoin Drugs 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 238000012332 laboratory investigation 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
- FPKOGTAFKSLZLD-FQEVSTJZSA-N lamifiban Chemical compound C1=CC(C(=N)N)=CC=C1C(=O)N[C@H](C(=O)N1CCC(CC1)OCC(O)=O)CC1=CC=C(O)C=C1 FPKOGTAFKSLZLD-FQEVSTJZSA-N 0.000 description 1
- 229950003178 lamifiban Drugs 0.000 description 1
- 229960001627 lamivudine Drugs 0.000 description 1
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 229940095570 lescol Drugs 0.000 description 1
- UGFHIPBXIWJXNA-UHFFFAOYSA-N liarozole Chemical compound ClC1=CC=CC(C(C=2C=C3NC=NC3=CC=2)N2C=NC=C2)=C1 UGFHIPBXIWJXNA-UHFFFAOYSA-N 0.000 description 1
- 229950007056 liarozole Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 229940002661 lipitor Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 229950008991 lobaplatin Drugs 0.000 description 1
- 229950000909 lometrexol Drugs 0.000 description 1
- 229960003538 lonidamine Drugs 0.000 description 1
- WDRYRZXSPDWGEB-UHFFFAOYSA-N lonidamine Chemical compound C12=CC=CC=C2C(C(=O)O)=NN1CC1=CC=C(Cl)C=C1Cl WDRYRZXSPDWGEB-UHFFFAOYSA-N 0.000 description 1
- 229950010501 lotrafiban Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- RVFGKBWWUQOIOU-NDEPHWFRSA-N lurtotecan Chemical compound O=C([C@]1(O)CC)OCC(C(N2CC3=4)=O)=C1C=C2C3=NC1=CC=2OCCOC=2C=C1C=4CN1CCN(C)CC1 RVFGKBWWUQOIOU-NDEPHWFRSA-N 0.000 description 1
- 229950002654 lurtotecan Drugs 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 208000027202 mammary Paget disease Diseases 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- PSGAAPLEWMOORI-PEINSRQWSA-N medroxyprogesterone acetate Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 PSGAAPLEWMOORI-PEINSRQWSA-N 0.000 description 1
- 208000001223 meningeal tuberculosis Diseases 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 229940099246 mevacor Drugs 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 229950010913 mitolactol Drugs 0.000 description 1
- VFKZTMPDYBFSTM-GUCUJZIJSA-N mitolactol Chemical compound BrC[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CBr VFKZTMPDYBFSTM-GUCUJZIJSA-N 0.000 description 1
- 230000000394 mitotic effect Effects 0.000 description 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- UDGSVBYJWHOHNN-UHFFFAOYSA-N n',n'-diethylethane-1,2-diamine Chemical group CCN(CC)CCN UDGSVBYJWHOHNN-UHFFFAOYSA-N 0.000 description 1
- NJSMWLQOCQIOPE-OCHFTUDZSA-N n-[(e)-[10-[(e)-(4,5-dihydro-1h-imidazol-2-ylhydrazinylidene)methyl]anthracen-9-yl]methylideneamino]-4,5-dihydro-1h-imidazol-2-amine Chemical compound N1CCN=C1N\N=C\C(C1=CC=CC=C11)=C(C=CC=C2)C2=C1\C=N\NC1=NCCN1 NJSMWLQOCQIOPE-OCHFTUDZSA-N 0.000 description 1
- TVYPSLDUBVTDIS-FUOMVGGVSA-N n-[1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-methyloxolan-2-yl]-5-fluoro-2-oxopyrimidin-4-yl]-3,4,5-trimethoxybenzamide Chemical compound COC1=C(OC)C(OC)=CC(C(=O)NC=2C(=CN(C(=O)N=2)[C@H]2[C@@H]([C@H](O)[C@@H](C)O2)O)F)=C1 TVYPSLDUBVTDIS-FUOMVGGVSA-N 0.000 description 1
- ZDUZYDDAHVZGCI-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]-9-hydroxy-5,6-dimethylpyrido[4,3-b]carbazole-1-carboxamide Chemical compound CN1C2=CC=C(O)C=C2C2=C1C(C)=C1C=CN=C(C(=O)NCCN(C)C)C1=C2 ZDUZYDDAHVZGCI-UHFFFAOYSA-N 0.000 description 1
- XBGNERSKEKDZDS-UHFFFAOYSA-N n-[2-(dimethylamino)ethyl]acridine-4-carboxamide Chemical compound C1=CC=C2N=C3C(C(=O)NCCN(C)C)=CC=CC3=CC2=C1 XBGNERSKEKDZDS-UHFFFAOYSA-N 0.000 description 1
- HKISSDWCMYSFSO-UHFFFAOYSA-N n-[3-methoxy-5-(trifluoromethyl)phenyl]-4-(2-phenylimidazol-1-yl)pyrimidin-2-amine Chemical compound FC(F)(F)C1=CC(OC)=CC(NC=2N=C(C=CN=2)N2C(=NC=C2)C=2C=CC=CC=2)=C1 HKISSDWCMYSFSO-UHFFFAOYSA-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
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 229950007221 nedaplatin Drugs 0.000 description 1
- 230000014399 negative regulation of angiogenesis Effects 0.000 description 1
- 230000017066 negative regulation of growth Effects 0.000 description 1
- 229960000801 nelarabine Drugs 0.000 description 1
- IXOXBSCIXZEQEQ-UHTZMRCNSA-N nelarabine Chemical compound C1=NC=2C(OC)=NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O IXOXBSCIXZEQEQ-UHTZMRCNSA-N 0.000 description 1
- 229960000884 nelfinavir Drugs 0.000 description 1
- QAGYKUNXZHXKMR-HKWSIXNMSA-N nelfinavir Chemical compound CC1=C(O)C=CC=C1C(=O)N[C@H]([C@H](O)CN1[C@@H](C[C@@H]2CCCC[C@@H]2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-HKWSIXNMSA-N 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229960000689 nevirapine Drugs 0.000 description 1
- 229960002653 nilutamide Drugs 0.000 description 1
- XWXYUMMDTVBTOU-UHFFFAOYSA-N nilutamide Chemical compound O=C1C(C)(C)NC(=O)N1C1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 XWXYUMMDTVBTOU-UHFFFAOYSA-N 0.000 description 1
- 229960001420 nimustine Drugs 0.000 description 1
- VFEDRRNHLBGPNN-UHFFFAOYSA-N nimustine Chemical compound CC1=NC=C(CNC(=O)N(CCCl)N=O)C(N)=N1 VFEDRRNHLBGPNN-UHFFFAOYSA-N 0.000 description 1
- XHWRWCSCBDLOLM-UHFFFAOYSA-N nolatrexed Chemical compound CC1=CC=C2NC(N)=NC(=O)C2=C1SC1=CC=NC=C1 XHWRWCSCBDLOLM-UHFFFAOYSA-N 0.000 description 1
- 229950000891 nolatrexed Drugs 0.000 description 1
- 230000000263 nonmitogenic effect Effects 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 210000002997 osteoclast Anatomy 0.000 description 1
- 230000001599 osteoclastic effect Effects 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 239000001301 oxygen Substances 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
- 230000003076 paracrine Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229960005079 pemetrexed Drugs 0.000 description 1
- QOFFJEBXNKRSPX-ZDUSSCGKSA-N pemetrexed Chemical compound C1=N[C]2NC(N)=NC(=O)C2=C1CCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 QOFFJEBXNKRSPX-ZDUSSCGKSA-N 0.000 description 1
- 229960002340 pentostatin Drugs 0.000 description 1
- FPVKHBSQESCIEP-JQCXWYLXSA-N pentostatin Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC[C@H]2O)=C2N=C1 FPVKHBSQESCIEP-JQCXWYLXSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000005561 phenanthryl group Chemical group 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 125000004344 phenylpropyl group Chemical group 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 229950004317 pinafide Drugs 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229960001221 pirarubicin Drugs 0.000 description 1
- 229950008499 plitidepsin Drugs 0.000 description 1
- UUSZLLQJYRSZIS-LXNNNBEUSA-N plitidepsin Chemical compound CN([C@H](CC(C)C)C(=O)N[C@@H]1C(=O)N[C@@H]([C@H](CC(=O)O[C@H](C(=O)[C@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N2CCC[C@H]2C(=O)N(C)[C@@H](CC=2C=CC(OC)=CC=2)C(=O)O[C@@H]1C)C(C)C)O)[C@@H](C)CC)C(=O)[C@@H]1CCCN1C(=O)C(C)=O UUSZLLQJYRSZIS-LXNNNBEUSA-N 0.000 description 1
- 108010049948 plitidepsin Proteins 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229940089484 pravachol Drugs 0.000 description 1
- 229960002965 pravastatin Drugs 0.000 description 1
- 229960004694 prednimustine Drugs 0.000 description 1
- 229940063238 premarin Drugs 0.000 description 1
- 238000011809 primate model Methods 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 238000001742 protein purification Methods 0.000 description 1
- 229940126409 proton pump inhibitor Drugs 0.000 description 1
- 239000000612 proton pump inhibitor Substances 0.000 description 1
- 229950007401 pumitepa Drugs 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 1
- FREJAOSUHFGDBW-UHFFFAOYSA-N pyrimidine-5-carbaldehyde Chemical compound O=CC1=CN=CN=C1 FREJAOSUHFGDBW-UHFFFAOYSA-N 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 229960004432 raltitrexed Drugs 0.000 description 1
- 229960002185 ranimustine Drugs 0.000 description 1
- 229950007649 ranpirnase Drugs 0.000 description 1
- 108010061338 ranpirnase Proteins 0.000 description 1
- 108010014186 ras Proteins Proteins 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 208000004644 retinal vein occlusion Diseases 0.000 description 1
- 229940100552 retinamide Drugs 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- OWPCHSCAPHNHAV-LMONGJCWSA-N rhizoxin Chemical compound C/C([C@H](OC)[C@@H](C)[C@@H]1C[C@H](O)[C@]2(C)O[C@@H]2/C=C/[C@@H](C)[C@]2([H])OC(=O)C[C@@](C2)(C[C@@H]2O[C@H]2C(=O)O1)[H])=C\C=C\C(\C)=C\C1=COC(C)=N1 OWPCHSCAPHNHAV-LMONGJCWSA-N 0.000 description 1
- 229940089617 risedronate Drugs 0.000 description 1
- 229960000311 ritonavir Drugs 0.000 description 1
- NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 description 1
- 238000011808 rodent model Methods 0.000 description 1
- 229960000371 rofecoxib Drugs 0.000 description 1
- VHXNKPBCCMUMSW-FQEVSTJZSA-N rubitecan Chemical compound C1=CC([N+]([O-])=O)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VHXNKPBCCMUMSW-FQEVSTJZSA-N 0.000 description 1
- 229950009213 rubitecan Drugs 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 229960001852 saquinavir Drugs 0.000 description 1
- QWAXKHKRTORLEM-UGJKXSETSA-N saquinavir Chemical compound C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 QWAXKHKRTORLEM-UGJKXSETSA-N 0.000 description 1
- 229960005399 satraplatin Drugs 0.000 description 1
- 190014017285 satraplatin Chemical compound 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- WUWDLXZGHZSWQZ-WQLSENKSSA-N semaxanib Chemical compound N1C(C)=CC(C)=C1\C=C/1C2=CC=CC=C2NC\1=O WUWDLXZGHZSWQZ-WQLSENKSSA-N 0.000 description 1
- 229950005747 sibrafiban Drugs 0.000 description 1
- 229950010372 sobuzoxane Drugs 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 108010087686 src-Family Kinases Proteins 0.000 description 1
- 102000009076 src-Family Kinases Human genes 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000005017 substituted alkenyl group Chemical group 0.000 description 1
- 125000004426 substituted alkynyl group Chemical group 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 229960005566 swainsonine Drugs 0.000 description 1
- FXUAIOOAOAVCGD-FKSUSPILSA-N swainsonine Chemical compound C1CC[C@H](O)[C@H]2[C@H](O)[C@H](O)CN21 FXUAIOOAOAVCGD-FKSUSPILSA-N 0.000 description 1
- FXUAIOOAOAVCGD-UHFFFAOYSA-N swainsonine Natural products C1CCC(O)C2C(O)C(O)CN21 FXUAIOOAOAVCGD-UHFFFAOYSA-N 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- AYUNIORJHRXIBJ-TXHRRWQRSA-N tanespimycin Chemical compound N1C(=O)\C(C)=C\C=C/[C@H](OC)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@@H](O)[C@@H](OC)C[C@H](C)CC2=C(NCC=C)C(=O)C=C1C2=O AYUNIORJHRXIBJ-TXHRRWQRSA-N 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 229960003102 tasonermin Drugs 0.000 description 1
- 229960001674 tegafur Drugs 0.000 description 1
- WFWLQNSHRPWKFK-ZCFIWIBFSA-N tegafur Chemical compound O=C1NC(=O)C(F)=CN1[C@@H]1OCCC1 WFWLQNSHRPWKFK-ZCFIWIBFSA-N 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 229960004964 temozolomide Drugs 0.000 description 1
- 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 1
- 229960001278 teniposide Drugs 0.000 description 1
- 229950002757 teoclate Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- BEUUJDAEPJZWHM-COROXYKFSA-N tert-butyl n-[(2s,3s,5r)-3-hydroxy-6-[[(2s)-1-(2-methoxyethylamino)-3-methyl-1-oxobutan-2-yl]amino]-6-oxo-1-phenyl-5-[(2,3,4-trimethoxyphenyl)methyl]hexan-2-yl]carbamate Chemical compound C([C@@H]([C@@H](O)C[C@H](C(=O)N[C@H](C(=O)NCCOC)C(C)C)CC=1C(=C(OC)C(OC)=CC=1)OC)NC(=O)OC(C)(C)C)C1=CC=CC=C1 BEUUJDAEPJZWHM-COROXYKFSA-N 0.000 description 1
- AZKCOMYNMXGCRZ-UHFFFAOYSA-N tert-butyl n-[3-[(4-acetylpiperazin-1-yl)methyl]-5-methylphenyl]carbamate Chemical compound C1CN(C(=O)C)CCN1CC1=CC(C)=CC(NC(=O)OC(C)(C)C)=C1 AZKCOMYNMXGCRZ-UHFFFAOYSA-N 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 1
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 229960003723 tiazofurine Drugs 0.000 description 1
- FVRDYQYEVDDKCR-DBRKOABJSA-N tiazofurine Chemical compound NC(=O)C1=CSC([C@H]2[C@@H]([C@H](O)[C@@H](CO)O2)O)=N1 FVRDYQYEVDDKCR-DBRKOABJSA-N 0.000 description 1
- 229960000838 tipranavir Drugs 0.000 description 1
- SUJUHGSWHZTSEU-FYBSXPHGSA-N tipranavir Chemical compound C([C@@]1(CCC)OC(=O)C([C@H](CC)C=2C=C(NS(=O)(=O)C=3N=CC(=CC=3)C(F)(F)F)C=CC=2)=C(O)C1)CC1=CC=CC=C1 SUJUHGSWHZTSEU-FYBSXPHGSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
- 229960005026 toremifene Drugs 0.000 description 1
- XFCLJVABOIYOMF-QPLCGJKRSA-N toremifene Chemical compound C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 XFCLJVABOIYOMF-QPLCGJKRSA-N 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
- 102000027257 transmembrane receptors Human genes 0.000 description 1
- 108091008578 transmembrane receptors Proteins 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- 229960005526 triapine Drugs 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 229960001099 trimetrexate Drugs 0.000 description 1
- NOYPYLRCIDNJJB-UHFFFAOYSA-N trimetrexate Chemical compound COC1=C(OC)C(OC)=CC(NCC=2C(=C3C(N)=NC(N)=NC3=CC=2)C)=C1 NOYPYLRCIDNJJB-UHFFFAOYSA-N 0.000 description 1
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
- 229960000875 trofosfamide Drugs 0.000 description 1
- UMKFEPPTGMDVMI-UHFFFAOYSA-N trofosfamide Chemical compound ClCCN(CCCl)P1(=O)OCCCN1CCCl UMKFEPPTGMDVMI-UHFFFAOYSA-N 0.000 description 1
- 229950010147 troxacitabine Drugs 0.000 description 1
- RXRGZNYSEHTMHC-BQBZGAKWSA-N troxacitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)OC1 RXRGZNYSEHTMHC-BQBZGAKWSA-N 0.000 description 1
- 230000005747 tumor angiogenesis Effects 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 229960000653 valrubicin Drugs 0.000 description 1
- ZOCKGBMQLCSHFP-KQRAQHLDSA-N valrubicin Chemical compound O([C@H]1C[C@](CC2=C(O)C=3C(=O)C4=CC=CC(OC)=C4C(=O)C=3C(O)=C21)(O)C(=O)COC(=O)CCCC)[C@H]1C[C@H](NC(=O)C(F)(F)F)[C@H](O)[C@H](C)O1 ZOCKGBMQLCSHFP-KQRAQHLDSA-N 0.000 description 1
- 230000006444 vascular growth Effects 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 230000004862 vasculogenesis Effects 0.000 description 1
- YCOYDOIWSSHVCK-UHFFFAOYSA-N vatalanib Chemical compound C1=CC(Cl)=CC=C1NC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 YCOYDOIWSSHVCK-UHFFFAOYSA-N 0.000 description 1
- 229960005212 vindesine sulfate Drugs 0.000 description 1
- NMDYYWFGPIMTKO-HBVLKOHWSA-N vinflunine Chemical compound C([C@@](C1=C(C2=CC=CC=C2N1)C1)(C2=C(OC)C=C3N(C)[C@@H]4[C@@]5(C3=C2)CCN2CC=C[C@]([C@@H]52)([C@H]([C@]4(O)C(=O)OC)OC(C)=O)CC)C(=O)OC)[C@H]2C[C@@H](C(C)(F)F)CN1C2 NMDYYWFGPIMTKO-HBVLKOHWSA-N 0.000 description 1
- 229960000922 vinflunine Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 229960002555 zidovudine Drugs 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229940072168 zocor Drugs 0.000 description 1
- 229960000641 zorubicin Drugs 0.000 description 1
- FBTUMDXHSRTGRV-ALTNURHMSA-N zorubicin 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)=N\NC(=O)C=1C=CC=CC=1)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 FBTUMDXHSRTGRV-ALTNURHMSA-N 0.000 description 1
- VLCYCQAOQCDTCN-ZCFIWIBFSA-N α-difluoromethylornithine Chemical compound NCCC[C@@](N)(C(F)F)C(O)=O VLCYCQAOQCDTCN-ZCFIWIBFSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Abstract
Description
Claims
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/485,170 US6958340B2 (en) | 2001-08-01 | 2002-07-26 | Tyrosine kinase inhibitors |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US30940001P | 2001-08-01 | 2001-08-01 | |
US60/309,400 | 2001-08-01 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2003011836A1 true WO2003011836A1 (en) | 2003-02-13 |
Family
ID=23198073
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2002/023764 WO2003011836A1 (en) | 2001-08-01 | 2002-07-26 | Tyrosine kinase inhibitors |
Country Status (2)
Country | Link |
---|---|
US (1) | US6958340B2 (en) |
WO (1) | WO2003011836A1 (en) |
Cited By (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005068437A1 (en) * | 2004-01-16 | 2005-07-28 | Novartis Ag | 2, 4 - diaminopyrimidines and their use for inducing cardiomyogenesis |
WO2005070932A2 (en) * | 2004-01-22 | 2005-08-04 | Amgen Inc. | Substituted heterocyclic compounds and methods of use |
WO2006049304A1 (en) | 2004-11-02 | 2006-05-11 | Banyu Pharmaceutical Co., Ltd | Aryloxy-substituted benzimidazole derivatives |
US7109204B2 (en) | 2001-08-01 | 2006-09-19 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
WO2007018325A1 (en) * | 2005-08-05 | 2007-02-15 | Il-Yang Pharm. Co., Ltd. | N-phenyl-2-pyrimidine-amine derivatives and process for the preparation thereof |
US7414059B2 (en) | 2003-11-24 | 2008-08-19 | Roche Palo Alto Llc | Pyrazolyl and imidazolyl pyrimidines as CRF antagonists |
JP2010536865A (en) * | 2007-08-22 | 2010-12-02 | アイアールエム・リミテッド・ライアビリティ・カンパニー | 2-Heteroarylamino-pyrimidine derivatives which are kinase inhibitors |
US7855205B2 (en) | 2004-10-29 | 2010-12-21 | Janssen Pharmaceutica Nv | Pyrimidinyl substituted fused-pyrrolyl compounds useful in treating kinase disorders |
US8569305B2 (en) | 2002-09-05 | 2013-10-29 | Emory University | Treatment of tuberous sclerosis associated neoplasms |
WO2018056621A1 (en) * | 2016-09-23 | 2018-03-29 | 재단법인 대구경북첨단의료산업진흥재단 | Novel imidazolyl pyrimidine derivative, method for preparing same, and pharmaceutical composition comprising same as active ingredient for prevention or treatment of cancer |
CN108699041A (en) * | 2016-01-29 | 2018-10-23 | 三进制药株式会社 | Novel imidazole derivatives and application thereof with JNK inhibitory activity |
CN110041302A (en) * | 2019-03-01 | 2019-07-23 | 南方医科大学 | 2- amino -4- substituted pyridine derivative and its synthetic method and application |
WO2020022787A1 (en) * | 2018-07-24 | 2020-01-30 | 삼진제약주식회사 | Novel imidazole derivative having jnk inhibitory activity, and pharmaceutical composition comprising same |
US10683293B2 (en) | 2014-08-04 | 2020-06-16 | Nuevolution A/S | Optionally fused heterocyclyl-substituted derivatives of pyrimidine useful for the treatment of inflammatory, metabolic, oncologic and autoimmune diseases |
US11066404B2 (en) | 2018-10-11 | 2021-07-20 | Incyte Corporation | Dihydropyrido[2,3-d]pyrimidinone compounds as CDK2 inhibitors |
US11384083B2 (en) | 2019-02-15 | 2022-07-12 | Incyte Corporation | Substituted spiro[cyclopropane-1,5′-pyrrolo[2,3-d]pyrimidin]-6′(7′h)-ones as CDK2 inhibitors |
US11427567B2 (en) | 2019-08-14 | 2022-08-30 | Incyte Corporation | Imidazolyl pyrimidinylamine compounds as CDK2 inhibitors |
US11440914B2 (en) | 2019-05-01 | 2022-09-13 | Incyte Corporation | Tricyclic amine compounds as CDK2 inhibitors |
US11447479B2 (en) | 2019-12-20 | 2022-09-20 | Nuevolution A/S | Compounds active towards nuclear receptors |
US11447494B2 (en) | 2019-05-01 | 2022-09-20 | Incyte Corporation | Tricyclic amine compounds as CDK2 inhibitors |
US11472791B2 (en) | 2019-03-05 | 2022-10-18 | Incyte Corporation | Pyrazolyl pyrimidinylamine compounds as CDK2 inhibitors |
US11613532B2 (en) | 2020-03-31 | 2023-03-28 | Nuevolution A/S | Compounds active towards nuclear receptors |
US11780843B2 (en) | 2020-03-31 | 2023-10-10 | Nuevolution A/S | Compounds active towards nuclear receptors |
US11851426B2 (en) | 2019-10-11 | 2023-12-26 | Incyte Corporation | Bicyclic amines as CDK2 inhibitors |
US11919904B2 (en) | 2019-03-29 | 2024-03-05 | Incyte Corporation | Sulfonylamide compounds as CDK2 inhibitors |
US11976073B2 (en) | 2021-12-10 | 2024-05-07 | Incyte Corporation | Bicyclic amines as CDK2 inhibitors |
US11981671B2 (en) | 2022-06-21 | 2024-05-14 | Incyte Corporation | Bicyclic pyrazolyl amines as CDK2 inhibitors |
Families Citing this family (57)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7501948B2 (en) | 2004-09-29 | 2009-03-10 | Lone Star Ip Holdings, Lp | Interrogation system employing prior knowledge about an object to discern an identity thereof |
US20070258976A1 (en) * | 2006-05-04 | 2007-11-08 | Ward Keith W | Combination Therapy for Diseases Involving Angiogenesis |
US8080252B2 (en) * | 2006-07-19 | 2011-12-20 | The Cleveland Clinic Foundation | Compounds and methods of modulating angiogenesis |
WO2008011513A2 (en) * | 2006-07-19 | 2008-01-24 | The Cleveland Clinic Foundation | Compounds and methods of modulating angiogenesis |
US8246966B2 (en) * | 2006-08-07 | 2012-08-21 | University Of Georgia Research Foundation, Inc. | Trypanosome microsome system and uses thereof |
CA2669531A1 (en) | 2006-11-22 | 2008-06-05 | University Of Georgia Research Foundation, Inc. | Tyrosine kinase inhibitors as anti-kinetolastid and anti-apicomplexan agents |
DK2769737T3 (en) | 2009-07-20 | 2017-07-24 | Bristol Myers Squibb Co | COMBINATION OF ANTI-CTLA4 ANTIBODY WITH ETOPOSIDE FOR SYNERGISTIC TREATMENT OF PROLIFERATIVE DISEASES |
CA2777934A1 (en) | 2009-10-20 | 2011-04-28 | Prometheus Laboratories Inc. | Proximity-mediated assays for detecting oncogenic fusion proteins |
US20110189174A1 (en) | 2010-02-01 | 2011-08-04 | Afshin Shafiee | Compositions and methods for treating, reducing, ameliorating, alleviating, or inhibiting progression of, pathogenic ocular neovascularization |
WO2012154257A1 (en) | 2011-02-17 | 2012-11-15 | Prometheus Laboratories Inc. | Apparatus and method for isolating leukocytes and tumor cells by filtration |
US8921533B2 (en) | 2011-07-25 | 2014-12-30 | Chromatin Technologies | Glycosylated valproic acid analogs and uses thereof |
PE20142406A1 (en) | 2012-05-04 | 2015-01-23 | Pfizer | ANTIGENS ASSOCIATED WITH PROSTATE AND VACCINE-BASED IMMUNOTHERAPY REGIMES |
CN106211774B (en) | 2013-08-02 | 2020-11-06 | 辉瑞公司 | anti-CXCR 4 antibodies and antibody-drug conjugates |
WO2016063122A1 (en) | 2014-10-20 | 2016-04-28 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for screening a subject for a cancer |
EP3229836B1 (en) | 2014-12-09 | 2019-11-13 | Institut National de la Sante et de la Recherche Medicale (INSERM) | Human monoclonal antibodies against axl |
WO2016135041A1 (en) | 2015-02-26 | 2016-09-01 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Fusion proteins and antibodies comprising thereof for promoting apoptosis |
JP2018525029A (en) | 2015-07-07 | 2018-09-06 | インセルム(インスティチュート ナショナル デ ラ サンテ エ デ ラ リシェルシェ メディカル) | Antibody having specificity for myosin 18A and use thereof |
US11385231B2 (en) | 2015-08-27 | 2022-07-12 | Inserm (Institut National De La Sante Et De La Recherche Scientifique) | Methods for predicting the survival time of patients suffering from a lung cancer |
WO2017055327A1 (en) | 2015-09-29 | 2017-04-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for quantifying the population of endothelial cells in a tissue sample |
WO2017055326A1 (en) | 2015-09-29 | 2017-04-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for quantifying the population of myeloid dendritic cells in a tissue sample |
WO2017055324A1 (en) | 2015-09-29 | 2017-04-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for quantifying the population of cells of monocytic origin in a tissue sample |
WO2017055322A1 (en) | 2015-09-29 | 2017-04-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for quantifying the population of neutrophils in a tissue sample |
CA3013333A1 (en) | 2016-02-26 | 2017-08-31 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Antibodies having specificity for btla and uses thereof |
CA3025057A1 (en) | 2016-05-25 | 2017-11-30 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Methods and compositions for treating cancers |
WO2018011166A2 (en) | 2016-07-12 | 2018-01-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for quantifying the population of myeloid dendritic cells in a tissue sample |
BR112019001693A2 (en) | 2016-07-29 | 2019-07-02 | Ct Hospitalier Universitaire Toulouse | antibodies targeting tumor-associated macrophages and their uses |
EP3950709B1 (en) | 2016-10-21 | 2024-02-14 | OSE Immunotherapeutics | Methods for promoting t cells response |
WO2018087391A1 (en) | 2016-11-14 | 2018-05-17 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for modulating stem cells proliferation or differentiation |
CN110392697A (en) | 2017-03-02 | 2019-10-29 | 国家医疗保健研究所 | There is the antibody and application thereof of specificity to NECTIN-4 |
WO2018185516A1 (en) | 2017-04-05 | 2018-10-11 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for treating cardiovascular toxicity induced by anti-cancer therapy |
WO2018189403A1 (en) | 2017-04-14 | 2018-10-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment of cancer |
WO2018211007A1 (en) | 2017-05-18 | 2018-11-22 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment of mast cell diseases |
WO2019072885A1 (en) | 2017-10-11 | 2019-04-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Magnetic nanoparticles for the treatment of cancer |
WO2019072888A1 (en) | 2017-10-11 | 2019-04-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for predicting hepatocellular carcinoma treatment response |
US11679148B2 (en) | 2017-11-24 | 2023-06-20 | Institut National De La Santé Et De La Recherche Médicale (Inserm) | Methods and compositions for treating cancers |
US11814686B2 (en) | 2017-12-07 | 2023-11-14 | Institut National de la Santéde la Recherche Médicale | Method for screening and treating a subject for a cancer |
WO2019185683A1 (en) | 2018-03-28 | 2019-10-03 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for treating cancer |
JP2021521445A (en) | 2018-04-13 | 2021-08-26 | アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル | Methods for predicting and treating outcomes in patients with prostate or breast cancer |
WO2019211369A1 (en) | 2018-05-03 | 2019-11-07 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for treating cancer |
WO2019211370A1 (en) | 2018-05-03 | 2019-11-07 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for treating cancer |
CA3101694A1 (en) | 2018-05-30 | 2019-12-05 | David MACHOVER | Methods and pharmaceutical compositions for treating cancer |
WO2019234221A1 (en) | 2018-06-08 | 2019-12-12 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for stratification and treatment of a patient suffering from chronic lymphocytic leukemia |
US20210236633A1 (en) | 2018-08-06 | 2021-08-05 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating cancers |
EP3849602A1 (en) | 2018-09-10 | 2021-07-21 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Combination of her2/neu antibody with heme for treating cancer |
EP3924520A1 (en) | 2019-02-13 | 2021-12-22 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for selecting a cancer treatment in a subject suffering from cancer |
WO2020178400A1 (en) | 2019-03-06 | 2020-09-10 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Method to diagnose a cmmrd |
WO2020234399A1 (en) | 2019-05-20 | 2020-11-26 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Novel anti-cd25 antibodies |
EP4007820A1 (en) | 2019-08-02 | 2022-06-08 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Method for screening a subject for a cancer |
EP3800201A1 (en) | 2019-10-01 | 2021-04-07 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Cd28h stimulation enhances nk cell killing activities |
EP4072682A1 (en) | 2019-12-09 | 2022-10-19 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Antibodies having specificity to her4 and uses thereof |
EP4149558A1 (en) | 2020-05-12 | 2023-03-22 | INSERM (Institut National de la Santé et de la Recherche Médicale) | New method to treat cutaneous t-cell lymphomas and tfh derived lymphomas |
WO2022101463A1 (en) | 2020-11-16 | 2022-05-19 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of the last c-terminal residues m31/41 of zikv m ectodomain for triggering apoptotic cell death |
EP4284420A1 (en) | 2021-01-29 | 2023-12-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Method to diagnose msi cancer |
US20220389104A1 (en) | 2021-05-28 | 2022-12-08 | Ose Immunotherapeutics | Method for Treating CD127-Positive Cancers by Administering an Anti-CD127 Agent |
KR102660894B1 (en) | 2021-09-17 | 2024-04-26 | 기초과학연구원 | Method for producing pyrimidin-2-amine |
WO2024052503A1 (en) | 2022-09-08 | 2024-03-14 | Institut National de la Santé et de la Recherche Médicale | Antibodies having specificity to ltbp2 and uses thereof |
WO2024061930A1 (en) | 2022-09-22 | 2024-03-28 | Institut National de la Santé et de la Recherche Médicale | New method to treat and diagnose peripheral t-cell lymphoma (ptcl) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6200977B1 (en) * | 1998-02-17 | 2001-03-13 | Tularik Inc. | Pyrimidine derivatives |
US6410726B1 (en) * | 2000-01-12 | 2002-06-25 | Tularik Inc. | Arylsulfonic acid salts of pyrimidine-based antiviral |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1282606B1 (en) * | 2000-05-08 | 2015-04-22 | Janssen Pharmaceutica NV | Hiv replication inhibiting pyrimidines and triazines |
US20040171630A1 (en) | 2001-06-19 | 2004-09-02 | Yuntae Kim | Tyrosine kinase inhibitors |
WO2003011837A1 (en) | 2001-08-01 | 2003-02-13 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
US20040181066A1 (en) | 2001-08-01 | 2004-09-16 | Fraley Mark E. | Tyrosine kinase inhibitors |
-
2002
- 2002-07-26 WO PCT/US2002/023764 patent/WO2003011836A1/en not_active Application Discontinuation
- 2002-07-26 US US10/485,170 patent/US6958340B2/en not_active Expired - Fee Related
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6200977B1 (en) * | 1998-02-17 | 2001-03-13 | Tularik Inc. | Pyrimidine derivatives |
US6410726B1 (en) * | 2000-01-12 | 2002-06-25 | Tularik Inc. | Arylsulfonic acid salts of pyrimidine-based antiviral |
Cited By (41)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7109204B2 (en) | 2001-08-01 | 2006-09-19 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
US8569305B2 (en) | 2002-09-05 | 2013-10-29 | Emory University | Treatment of tuberous sclerosis associated neoplasms |
US7414059B2 (en) | 2003-11-24 | 2008-08-19 | Roche Palo Alto Llc | Pyrazolyl and imidazolyl pyrimidines as CRF antagonists |
WO2005068437A1 (en) * | 2004-01-16 | 2005-07-28 | Novartis Ag | 2, 4 - diaminopyrimidines and their use for inducing cardiomyogenesis |
US7504403B2 (en) | 2004-01-22 | 2009-03-17 | Amgen Inc. | Substituted heterocyclic compounds and methods of use |
WO2005070932A2 (en) * | 2004-01-22 | 2005-08-04 | Amgen Inc. | Substituted heterocyclic compounds and methods of use |
WO2005070932A3 (en) * | 2004-01-22 | 2005-10-27 | Amgen Inc | Substituted heterocyclic compounds and methods of use |
US7855205B2 (en) | 2004-10-29 | 2010-12-21 | Janssen Pharmaceutica Nv | Pyrimidinyl substituted fused-pyrrolyl compounds useful in treating kinase disorders |
WO2006049304A1 (en) | 2004-11-02 | 2006-05-11 | Banyu Pharmaceutical Co., Ltd | Aryloxy-substituted benzimidazole derivatives |
WO2007018325A1 (en) * | 2005-08-05 | 2007-02-15 | Il-Yang Pharm. Co., Ltd. | N-phenyl-2-pyrimidine-amine derivatives and process for the preparation thereof |
AU2005335298B2 (en) * | 2005-08-05 | 2010-05-27 | Il-Yang Pharm. Co., Ltd. | N-phenyl-2-pyrimidine-amine derivatives and process for the preparation thereof |
AU2005335298C1 (en) * | 2005-08-05 | 2010-11-25 | Il-Yang Pharm. Co., Ltd. | N-phenyl-2-pyrimidine-amine derivatives and process for the preparation thereof |
US7501424B2 (en) | 2005-08-05 | 2009-03-10 | Il-Yang Pharm. Co., Ltd. | N-phenyl-2-pyrimidine-amine derivatives and process for the preparation thereof |
EA015103B1 (en) * | 2005-08-05 | 2011-06-30 | Ил-Янг Фарм. Ко., Лтд. | N-phenyl-2-pyrimidine-amine derivatives and process for the preparation thereof |
JP2009503060A (en) * | 2005-08-05 | 2009-01-29 | イル−ヤン ファーム カンパニー リミテッド | N-phenyl-2-pyrimidin-amine derivative and process for its preparation |
JP2010536865A (en) * | 2007-08-22 | 2010-12-02 | アイアールエム・リミテッド・ライアビリティ・カンパニー | 2-Heteroarylamino-pyrimidine derivatives which are kinase inhibitors |
US11254681B2 (en) | 2014-08-04 | 2022-02-22 | Nuevolution A/S | Optionally fused heterocyclyl-substituted derivatives of pyrimidine useful for the treatment of inflammatory, metabolic, oncologic and autoimmune diseases |
US10689383B2 (en) | 2014-08-04 | 2020-06-23 | Nuevolution A/S | Optionally fused heterocyclyl-substituted derivatives of pyrimidine useful for the treatment of inflammatory, metabolic, oncologic and autoimmune diseases |
US10683293B2 (en) | 2014-08-04 | 2020-06-16 | Nuevolution A/S | Optionally fused heterocyclyl-substituted derivatives of pyrimidine useful for the treatment of inflammatory, metabolic, oncologic and autoimmune diseases |
CN108699041B (en) * | 2016-01-29 | 2021-03-26 | 三进制药株式会社 | Imidazole derivative having JNK inhibitory activity and use thereof |
CN108699041A (en) * | 2016-01-29 | 2018-10-23 | 三进制药株式会社 | Novel imidazole derivatives and application thereof with JNK inhibitory activity |
KR102030886B1 (en) * | 2016-09-23 | 2019-10-10 | 재단법인 대구경북첨단의료산업진흥재단 | Novel imidazolyl pyrimidine derivatives, preparation method thereof, and pharmaceutical composition for use in preventing or treating cancer containing the same as an active ingredient |
KR20180032784A (en) * | 2016-09-23 | 2018-04-02 | 재단법인 대구경북첨단의료산업진흥재단 | Novel imidazolyl pyrimidine derivatives, preparation method thereof, and pharmaceutical composition for use in preventing or treating cancer containing the same as an active ingredient |
WO2018056621A1 (en) * | 2016-09-23 | 2018-03-29 | 재단법인 대구경북첨단의료산업진흥재단 | Novel imidazolyl pyrimidine derivative, method for preparing same, and pharmaceutical composition comprising same as active ingredient for prevention or treatment of cancer |
WO2020022787A1 (en) * | 2018-07-24 | 2020-01-30 | 삼진제약주식회사 | Novel imidazole derivative having jnk inhibitory activity, and pharmaceutical composition comprising same |
US11066404B2 (en) | 2018-10-11 | 2021-07-20 | Incyte Corporation | Dihydropyrido[2,3-d]pyrimidinone compounds as CDK2 inhibitors |
US11866432B2 (en) | 2018-10-11 | 2024-01-09 | Incyte Corporation | Dihydropyrido[2,3-d]pyrimidinone compounds as CDK2 inhibitors |
US11384083B2 (en) | 2019-02-15 | 2022-07-12 | Incyte Corporation | Substituted spiro[cyclopropane-1,5′-pyrrolo[2,3-d]pyrimidin]-6′(7′h)-ones as CDK2 inhibitors |
CN110041302A (en) * | 2019-03-01 | 2019-07-23 | 南方医科大学 | 2- amino -4- substituted pyridine derivative and its synthetic method and application |
CN110041302B (en) * | 2019-03-01 | 2021-11-30 | 南方医科大学 | 2-amino-4-substituted pyridine derivative and synthesis method and application thereof |
US11472791B2 (en) | 2019-03-05 | 2022-10-18 | Incyte Corporation | Pyrazolyl pyrimidinylamine compounds as CDK2 inhibitors |
US11919904B2 (en) | 2019-03-29 | 2024-03-05 | Incyte Corporation | Sulfonylamide compounds as CDK2 inhibitors |
US11440914B2 (en) | 2019-05-01 | 2022-09-13 | Incyte Corporation | Tricyclic amine compounds as CDK2 inhibitors |
US11447494B2 (en) | 2019-05-01 | 2022-09-20 | Incyte Corporation | Tricyclic amine compounds as CDK2 inhibitors |
US11427567B2 (en) | 2019-08-14 | 2022-08-30 | Incyte Corporation | Imidazolyl pyrimidinylamine compounds as CDK2 inhibitors |
US11851426B2 (en) | 2019-10-11 | 2023-12-26 | Incyte Corporation | Bicyclic amines as CDK2 inhibitors |
US11447479B2 (en) | 2019-12-20 | 2022-09-20 | Nuevolution A/S | Compounds active towards nuclear receptors |
US11613532B2 (en) | 2020-03-31 | 2023-03-28 | Nuevolution A/S | Compounds active towards nuclear receptors |
US11780843B2 (en) | 2020-03-31 | 2023-10-10 | Nuevolution A/S | Compounds active towards nuclear receptors |
US11976073B2 (en) | 2021-12-10 | 2024-05-07 | Incyte Corporation | Bicyclic amines as CDK2 inhibitors |
US11981671B2 (en) | 2022-06-21 | 2024-05-14 | Incyte Corporation | Bicyclic pyrazolyl amines as CDK2 inhibitors |
Also Published As
Publication number | Publication date |
---|---|
US20040220201A1 (en) | 2004-11-04 |
US6958340B2 (en) | 2005-10-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6958340B2 (en) | Tyrosine kinase inhibitors | |
US7109204B2 (en) | Tyrosine kinase inhibitors | |
EP1259235B1 (en) | Tyrosine kinase inhibitors | |
US6927293B2 (en) | Tyrosine kinase inhibitors | |
US6313138B1 (en) | Tyrosine kinase inhibitors | |
EP1226119B1 (en) | Tyrosine kinase inhibitors | |
EP1226136B1 (en) | Tyrosine kinase inhibitors | |
US6544988B1 (en) | Tyrosine kinase inhibitors | |
US20040171630A1 (en) | Tyrosine kinase inhibitors | |
US7265134B2 (en) | Tyrosine kinase inhibitors | |
US7169788B2 (en) | Tyrosine kinase inhibitors | |
US20050070546A1 (en) | Tyrosine kinase inhibitors | |
US20020137755A1 (en) | Tyrosine kinase inhibitors | |
US20040235867A1 (en) | Tyrosine kinase inhibitors | |
WO2003024931A1 (en) | Tyrosine kinase inhibitors | |
US20040181066A1 (en) | Tyrosine kinase inhibitors | |
WO2001062252A1 (en) | Tyrosine kinase inhibitors | |
WO2003020699A2 (en) | Tyrosine kinase inhibitors |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SD SE SG SI SK SL TJ TM TN TR TT TZ UA UG US UZ VN YU ZA ZM ZW Kind code of ref document: A1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BY BZ CA CH CN CO CR CU CZ DE DM DZ EC EE ES FI GB GD GE GH HR HU ID IL IN IS JP KE KG KR KZ LK LR LS LT LU LV MA MD MG MK MW MX MZ NO NZ OM PH PL PT RO SD SE SG SI SK SL TJ TM TN TR TT UA UG US UZ VN YU ZA ZM |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GH GM KE LS MW MZ SD SL SZ UG ZM ZW AM AZ BY KG KZ RU TJ TM AT BE BG CH CY CZ DK EE ES FI FR GB GR IE IT LU MC PT SE SK TR BF BJ CF CG CI GA GN GQ GW ML MR NE SN TD TG Kind code of ref document: A1 Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR IE IT LU MC NL PT SE SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
WWE | Wipo information: entry into national phase |
Ref document number: 10485170 Country of ref document: US |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
122 | Ep: pct application non-entry in european phase | ||
NENP | Non-entry into the national phase |
Ref country code: JP |
|
WWW | Wipo information: withdrawn in national office |
Country of ref document: JP |