UA124554C2 - ДЕЙТЕРОВАНІ СПОЛУКИ ІМІДАЗО[4,5-c]ХІНОЛІН-2-ОНУ ТА ЇХ ЗАСТОСУВАННЯ В ЛІКУВАННІ РАКУ - Google Patents
ДЕЙТЕРОВАНІ СПОЛУКИ ІМІДАЗО[4,5-c]ХІНОЛІН-2-ОНУ ТА ЇХ ЗАСТОСУВАННЯ В ЛІКУВАННІ РАКУ Download PDFInfo
- Publication number
- UA124554C2 UA124554C2 UAA201910213A UAA201910213A UA124554C2 UA 124554 C2 UA124554 C2 UA 124554C2 UA A201910213 A UAA201910213 A UA A201910213A UA A201910213 A UAA201910213 A UA A201910213A UA 124554 C2 UA124554 C2 UA 124554C2
- Authority
- UA
- Ukraine
- Prior art keywords
- compound
- cancer
- formula
- pharmaceutically acceptable
- acceptable salt
- Prior art date
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 125
- 201000011510 cancer Diseases 0.000 title claims abstract description 117
- NSHFLKZNBPJNPA-UHFFFAOYSA-N imidazo[4,5-c]quinolin-2-one Chemical class C1=CC=C2C3=NC(=O)N=C3C=NC2=C1 NSHFLKZNBPJNPA-UHFFFAOYSA-N 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 192
- 150000003839 salts Chemical class 0.000 claims abstract description 139
- 238000011282 treatment Methods 0.000 claims abstract description 73
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 14
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 claims description 55
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims description 27
- 238000000034 method Methods 0.000 claims description 26
- 241001465754 Metazoa Species 0.000 claims description 23
- 208000005017 glioblastoma Diseases 0.000 claims description 22
- 206010006187 Breast cancer Diseases 0.000 claims description 20
- 208000026310 Breast neoplasm Diseases 0.000 claims description 20
- 206010009944 Colon cancer Diseases 0.000 claims description 19
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 19
- 238000001959 radiotherapy Methods 0.000 claims description 19
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 17
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 claims description 16
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 claims description 16
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 14
- 206010017758 gastric cancer Diseases 0.000 claims description 14
- 229960004768 irinotecan Drugs 0.000 claims description 14
- 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 claims description 14
- 201000011549 stomach cancer Diseases 0.000 claims description 14
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 13
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 claims description 13
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 13
- 206010033128 Ovarian cancer Diseases 0.000 claims description 13
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 13
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 13
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 claims description 13
- 229960004679 doxorubicin Drugs 0.000 claims description 13
- 229940079593 drug Drugs 0.000 claims description 13
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 13
- 238000002560 therapeutic procedure Methods 0.000 claims description 13
- 206010041067 Small cell lung cancer Diseases 0.000 claims description 12
- 208000000587 small cell lung carcinoma Diseases 0.000 claims description 12
- 229960000303 topotecan Drugs 0.000 claims description 12
- 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 claims description 12
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 claims description 11
- 229960005420 etoposide Drugs 0.000 claims description 11
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 claims description 11
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 11
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 11
- 108010006654 Bleomycin Proteins 0.000 claims description 10
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 claims description 10
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 10
- YTKUWDBFDASYHO-UHFFFAOYSA-N bendamustine Chemical compound ClCCN(CCCl)C1=CC=C2N(C)C(CCCC(O)=O)=NC2=C1 YTKUWDBFDASYHO-UHFFFAOYSA-N 0.000 claims description 10
- 229960002707 bendamustine Drugs 0.000 claims description 10
- 229960001561 bleomycin Drugs 0.000 claims description 10
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 claims description 10
- 229960005243 carmustine Drugs 0.000 claims description 10
- 229960004630 chlorambucil Drugs 0.000 claims description 10
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 claims description 10
- 229960004397 cyclophosphamide Drugs 0.000 claims description 10
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 claims description 10
- 229960001924 melphalan Drugs 0.000 claims description 10
- 229960004857 mitomycin Drugs 0.000 claims description 10
- 239000000126 substance Substances 0.000 claims description 10
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 9
- 229930192392 Mitomycin Natural products 0.000 claims description 9
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 9
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 9
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 9
- 229960001101 ifosfamide Drugs 0.000 claims description 9
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 claims description 9
- -1 irosfamide Chemical compound 0.000 claims description 9
- 229960000572 olaparib Drugs 0.000 claims description 8
- FAQDUNYVKQKNLD-UHFFFAOYSA-N olaparib Chemical compound FC1=CC=C(CC2=C3[CH]C=CC=C3C(=O)N=N2)C=C1C(=O)N(CC1)CCN1C(=O)C1CC1 FAQDUNYVKQKNLD-UHFFFAOYSA-N 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 7
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 claims description 6
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 claims description 6
- 229960002550 amrubicin Drugs 0.000 claims description 6
- 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 claims description 6
- 229960001904 epirubicin Drugs 0.000 claims description 6
- 230000000259 anti-tumor effect Effects 0.000 claims description 5
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 claims description 5
- 229960004562 carboplatin Drugs 0.000 claims description 5
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 5
- 229960004316 cisplatin Drugs 0.000 claims description 5
- 229960001756 oxaliplatin Drugs 0.000 claims description 5
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 claims description 5
- 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 claims description 4
- 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 claims description 4
- 229960000908 idarubicin Drugs 0.000 claims description 4
- 229960000653 valrubicin Drugs 0.000 claims description 4
- 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 claims description 4
- 208000023105 Huntington disease Diseases 0.000 claims description 3
- 241000511343 Chondrostoma nasus Species 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 26
- 201000010099 disease Diseases 0.000 abstract description 24
- 108010004586 Ataxia Telangiectasia Mutated Proteins Proteins 0.000 abstract description 11
- 230000001404 mediated effect Effects 0.000 abstract description 9
- 230000002265 prevention Effects 0.000 abstract description 3
- 210000004027 cell Anatomy 0.000 description 43
- XRKYMMUGXMWDAO-UHFFFAOYSA-N 2-(4-morpholinyl)-6-(1-thianthrenyl)-4-pyranone Chemical compound O1C(C=2C=3SC4=CC=CC=C4SC=3C=CC=2)=CC(=O)C=C1N1CCOCC1 XRKYMMUGXMWDAO-UHFFFAOYSA-N 0.000 description 40
- 239000000203 mixture Substances 0.000 description 38
- 239000007787 solid Substances 0.000 description 34
- 239000000463 material Substances 0.000 description 33
- 230000000694 effects Effects 0.000 description 31
- 239000003826 tablet Substances 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
- 238000005481 NMR spectroscopy Methods 0.000 description 28
- 229910052805 deuterium Inorganic materials 0.000 description 27
- 239000000243 solution Substances 0.000 description 26
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 25
- 206010027476 Metastases Diseases 0.000 description 24
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- 238000004458 analytical method Methods 0.000 description 21
- 239000002246 antineoplastic agent Substances 0.000 description 21
- 210000003169 central nervous system Anatomy 0.000 description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 208000037819 metastatic cancer Diseases 0.000 description 17
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 17
- 238000001819 mass spectrum Methods 0.000 description 16
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 16
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 15
- 239000003795 chemical substances by application Substances 0.000 description 15
- 239000003112 inhibitor Substances 0.000 description 15
- 239000011541 reaction mixture Substances 0.000 description 15
- 239000012298 atmosphere Substances 0.000 description 14
- 238000001914 filtration Methods 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 238000013459 approach Methods 0.000 description 12
- 230000005764 inhibitory process Effects 0.000 description 12
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 11
- 201000005202 lung cancer Diseases 0.000 description 11
- 208000020816 lung neoplasm Diseases 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
- 102000002804 Ataxia Telangiectasia Mutated Proteins Human genes 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 10
- 230000001413 cellular effect Effects 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 230000004913 activation Effects 0.000 description 9
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 9
- 239000000377 silicon dioxide Substances 0.000 description 9
- 208000003174 Brain Neoplasms Diseases 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 206010059282 Metastases to central nervous system Diseases 0.000 description 8
- 206010051696 Metastases to meninges Diseases 0.000 description 8
- 108091000080 Phosphotransferase Proteins 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 8
- 102000020233 phosphotransferase Human genes 0.000 description 8
- 238000005406 washing Methods 0.000 description 8
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 7
- 230000005782 double-strand break Effects 0.000 description 7
- 230000006870 function Effects 0.000 description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 7
- 238000011534 incubation Methods 0.000 description 7
- 229940098779 methanesulfonic acid Drugs 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 230000001093 anti-cancer Effects 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- 229940126601 medicinal product Drugs 0.000 description 5
- 229960005419 nitrogen Drugs 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 230000026731 phosphorylation Effects 0.000 description 5
- 238000006366 phosphorylation reaction Methods 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- 208000024891 symptom Diseases 0.000 description 5
- KPPCEAKCGYAGGV-UHFFFAOYSA-N 5-bromo-2,4-difluorobenzoyl chloride Chemical compound FC1=CC(F)=C(C(Cl)=O)C=C1Br KPPCEAKCGYAGGV-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 206010003594 Ataxia telangiectasia Diseases 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 206010008342 Cervix carcinoma Diseases 0.000 description 4
- 206010014733 Endometrial cancer Diseases 0.000 description 4
- 206010014759 Endometrial neoplasm Diseases 0.000 description 4
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 102000001253 Protein Kinase Human genes 0.000 description 4
- 108091008611 Protein Kinase B Proteins 0.000 description 4
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 4
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 102100029823 Tyrosine-protein kinase BTK Human genes 0.000 description 4
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 201000010881 cervical cancer Diseases 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000009826 distribution Methods 0.000 description 4
- 201000004101 esophageal cancer Diseases 0.000 description 4
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 230000004060 metabolic process Effects 0.000 description 4
- 210000004940 nucleus Anatomy 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 108060006633 protein kinase Proteins 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- JPNPRWMRUCIEMN-UHFFFAOYSA-N 3-ditert-butylphosphaniumylpropane-1-sulfonate Chemical compound CC(C)(C)P(C(C)(C)C)CCCS(O)(=O)=O JPNPRWMRUCIEMN-UHFFFAOYSA-N 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 241000283707 Capra Species 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 239000006145 Eagle's minimal essential medium Substances 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 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 3
- 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000012131 assay buffer Substances 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- 239000002178 crystalline material Substances 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 150000001975 deuterium Chemical group 0.000 description 3
- 230000008030 elimination Effects 0.000 description 3
- 238000003379 elimination reaction Methods 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 238000009169 immunotherapy Methods 0.000 description 3
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 3
- 229940043355 kinase inhibitor Drugs 0.000 description 3
- 230000010534 mechanism of action Effects 0.000 description 3
- 210000002418 meninge Anatomy 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000004090 neuroprotective agent Substances 0.000 description 3
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 3
- 229960001221 pirarubicin Drugs 0.000 description 3
- 229950008882 polysorbate Drugs 0.000 description 3
- 229920000136 polysorbate Polymers 0.000 description 3
- 238000011321 prophylaxis Methods 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 235000012239 silicon dioxide Nutrition 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- KPZGRMZPZLOPBS-UHFFFAOYSA-N 1,3-dichloro-2,2-bis(chloromethyl)propane Chemical compound ClCC(CCl)(CCl)CCl KPZGRMZPZLOPBS-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- MYUQKYGWKHTRPG-UHFFFAOYSA-N 5-bromo-2-fluoropyridine Chemical compound FC1=CC=C(Br)C=N1 MYUQKYGWKHTRPG-UHFFFAOYSA-N 0.000 description 2
- VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- GUKAOHNCEOKUBL-UHFFFAOYSA-N BrC=1C=C2C(=C(C=NC2=CC1F)C(=O)N)Cl Chemical compound BrC=1C=C2C(=C(C=NC2=CC1F)C(=O)N)Cl GUKAOHNCEOKUBL-UHFFFAOYSA-N 0.000 description 2
- 230000012746 DNA damage checkpoint Effects 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 2
- 102000038030 PI3Ks Human genes 0.000 description 2
- 108091007960 PI3Ks Proteins 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000001099 ammonium carbonate Substances 0.000 description 2
- 239000004037 angiogenesis inhibitor Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000010533 azeotropic distillation Methods 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
- 229940092714 benzenesulfonic acid Drugs 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 230000027455 binding Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- 230000008777 canonical pathway Effects 0.000 description 2
- 238000000423 cell based assay Methods 0.000 description 2
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000013058 crude material Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000000113 differential scanning calorimetry Methods 0.000 description 2
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 238000010494 dissociation reaction Methods 0.000 description 2
- 230000005593 dissociations Effects 0.000 description 2
- 230000005670 electromagnetic radiation Effects 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- KGXQUPKOFCIFDQ-UHFFFAOYSA-N ethyl 6-bromo-4-chloro-7-fluoroquinoline-3-carboxylate Chemical compound C1=C(F)C(Br)=CC2=C(Cl)C(C(=O)OCC)=CN=C21 KGXQUPKOFCIFDQ-UHFFFAOYSA-N 0.000 description 2
- UCNRXGQAENVBFO-UHFFFAOYSA-N ethyl 6-bromo-7-fluoro-4-(propan-2-ylamino)quinoline-3-carboxylate Chemical compound BrC=1C=C2C(=C(C=NC2=CC=1F)C(=O)OCC)NC(C)C UCNRXGQAENVBFO-UHFFFAOYSA-N 0.000 description 2
- LMQDIXWMOUCVKZ-UHFFFAOYSA-N ethyl 6-bromo-7-fluoro-4-oxo-1h-quinoline-3-carboxylate Chemical compound C1=C(F)C(Br)=CC2=C(O)C(C(=O)OCC)=CN=C21 LMQDIXWMOUCVKZ-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 229960002949 fluorouracil Drugs 0.000 description 2
- VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 description 2
- 235000008191 folinic acid Nutrition 0.000 description 2
- 239000011672 folinic acid Substances 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 235000011087 fumaric acid Nutrition 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 239000002596 immunotoxin Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 230000000155 isotopic effect Effects 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 229960001691 leucovorin Drugs 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 230000000683 nonmetastatic effect Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 235000006408 oxalic acid Nutrition 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 238000000634 powder X-ray diffraction Methods 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 229940107700 pyruvic acid Drugs 0.000 description 2
- 230000028617 response to DNA damage stimulus Effects 0.000 description 2
- 239000011435 rock Substances 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- IRFHMTUHTBSEBK-QGZVFWFLSA-N tert-butyl n-[(2s)-2-(2,5-difluorophenyl)-3-quinolin-3-ylpropyl]carbamate Chemical compound C1([C@H](CC=2C=C3C=CC=CC3=NC=2)CNC(=O)OC(C)(C)C)=CC(F)=CC=C1F IRFHMTUHTBSEBK-QGZVFWFLSA-N 0.000 description 2
- 238000002411 thermogravimetry Methods 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- OJBYZWHAPXIJID-UHFFFAOYSA-N (6-fluoropyridin-3-yl)boronic acid Chemical compound OB(O)C1=CC=C(F)N=C1 OJBYZWHAPXIJID-UHFFFAOYSA-N 0.000 description 1
- KOFLVDBWRHFSAB-UHFFFAOYSA-N 1,2,4,5-tetrahydro-1-(phenylmethyl)-5,9b(1',2')-benzeno-9bh-benz(g)indol-3(3ah)-one Chemical compound C1C(C=2C3=CC=CC=2)C2=CC=CC=C2C23C1C(=O)CN2CC1=CC=CC=C1 KOFLVDBWRHFSAB-UHFFFAOYSA-N 0.000 description 1
- YRIZYWQGELRKNT-UHFFFAOYSA-N 1,3,5-trichloro-1,3,5-triazinane-2,4,6-trione Chemical compound ClN1C(=O)N(Cl)C(=O)N(Cl)C1=O YRIZYWQGELRKNT-UHFFFAOYSA-N 0.000 description 1
- PNDPGZBMCMUPRI-HVTJNCQCSA-N 10043-66-0 Chemical compound [131I][131I] PNDPGZBMCMUPRI-HVTJNCQCSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- HTFNVAVTYILUCF-UHFFFAOYSA-N 2-[2-ethoxy-4-[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]anilino]-5-methyl-11-methylsulfonylpyrimido[4,5-b][1,4]benzodiazepin-6-one Chemical compound CCOc1cc(ccc1Nc1ncc2N(C)C(=O)c3ccccc3N(c2n1)S(C)(=O)=O)C(=O)N1CCC(CC1)N1CCN(C)CC1 HTFNVAVTYILUCF-UHFFFAOYSA-N 0.000 description 1
- RTQWWZBSTRGEAV-PKHIMPSTSA-N 2-[[(2s)-2-[bis(carboxymethyl)amino]-3-[4-(methylcarbamoylamino)phenyl]propyl]-[2-[bis(carboxymethyl)amino]propyl]amino]acetic acid Chemical compound CNC(=O)NC1=CC=C(C[C@@H](CN(CC(C)N(CC(O)=O)CC(O)=O)CC(O)=O)N(CC(O)=O)CC(O)=O)C=C1 RTQWWZBSTRGEAV-PKHIMPSTSA-N 0.000 description 1
- UOXJNGFFPMOZDM-UHFFFAOYSA-N 2-[di(propan-2-yl)amino]ethylsulfanyl-methylphosphinic acid Chemical compound CC(C)N(C(C)C)CCSP(C)(O)=O UOXJNGFFPMOZDM-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 1
- MRWWWZLJWNIEEJ-UHFFFAOYSA-N 4,4,5,5-tetramethyl-2-propan-2-yloxy-1,3,2-dioxaborolane Chemical compound CC(C)OB1OC(C)(C)C(C)(C)O1 MRWWWZLJWNIEEJ-UHFFFAOYSA-N 0.000 description 1
- XXJWYDDUDKYVKI-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(1-pyrrolidinyl)propoxy]quinazoline Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)N=CN=C2C=C1OCCCN1CCCC1 XXJWYDDUDKYVKI-UHFFFAOYSA-N 0.000 description 1
- YTMVYYAKOPIJCZ-UHFFFAOYSA-N 4-bromo-3-fluoroaniline Chemical compound NC1=CC=C(Br)C(F)=C1 YTMVYYAKOPIJCZ-UHFFFAOYSA-N 0.000 description 1
- BLSMDXUAEFVYID-UHFFFAOYSA-N 5-bromo-2,4-difluorobenzoic acid Chemical compound OC(=O)C1=CC(Br)=C(F)C=C1F BLSMDXUAEFVYID-UHFFFAOYSA-N 0.000 description 1
- VHMSDSFDVVUVSI-UHFFFAOYSA-N 6-bromo-7-fluoro-4-(propan-2-ylamino)quinoline-3-carboxamide Chemical compound BrC=1C=C2C(=C(C=NC2=CC=1F)C(=O)N)NC(C)C VHMSDSFDVVUVSI-UHFFFAOYSA-N 0.000 description 1
- WJFWTHLXGGLRCI-UHFFFAOYSA-N 6-bromo-7-fluoro-4-(propan-2-ylamino)quinoline-3-carboxylic acid Chemical compound BrC=1C=C2C(=C(C=NC2=CC=1F)C(=O)O)NC(C)C WJFWTHLXGGLRCI-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
- BDDLHHRCDSJVKV-UHFFFAOYSA-N 7028-40-2 Chemical compound CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O BDDLHHRCDSJVKV-UHFFFAOYSA-N 0.000 description 1
- 239000012827 ATM inhibitor Substances 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 241000224489 Amoeba Species 0.000 description 1
- 102000009840 Angiopoietins Human genes 0.000 description 1
- 108010009906 Angiopoietins Proteins 0.000 description 1
- 102000012936 Angiostatins Human genes 0.000 description 1
- 108010079709 Angiostatins Proteins 0.000 description 1
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 description 1
- KTVIAHKRBVIUKU-UHFFFAOYSA-N BrC=1C=C2C(C(=CNC2=CC1F)C(=O)O)=O Chemical compound BrC=1C=C2C(C(=CNC2=CC1F)C(=O)O)=O KTVIAHKRBVIUKU-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-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
- 108010077544 Chromatin Proteins 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 239000012624 DNA alkylating agent Substances 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 230000008265 DNA repair mechanism Effects 0.000 description 1
- 108010006124 DNA-Activated Protein Kinase Proteins 0.000 description 1
- 102000005768 DNA-Activated Protein Kinase Human genes 0.000 description 1
- 108010092160 Dactinomycin Proteins 0.000 description 1
- 101100481404 Danio rerio tie1 gene Proteins 0.000 description 1
- WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 208000006402 Ductal Carcinoma Diseases 0.000 description 1
- 108010041308 Endothelial Growth Factors Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101001094649 Homo sapiens Popeye domain-containing protein 3 Proteins 0.000 description 1
- 101000608234 Homo sapiens Pyrin domain-containing protein 5 Proteins 0.000 description 1
- 101000729945 Homo sapiens Serine/threonine-protein kinase PLK2 Proteins 0.000 description 1
- 101000578693 Homo sapiens Target of rapamycin complex subunit LST8 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 102000004388 Interleukin-4 Human genes 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 238000003109 Karl Fischer titration Methods 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 239000002147 L01XE04 - Sunitinib Substances 0.000 description 1
- 239000005511 L01XE05 - Sorafenib Substances 0.000 description 1
- 239000003798 L01XE11 - Pazopanib Substances 0.000 description 1
- 239000002118 L01XE12 - Vandetanib Substances 0.000 description 1
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 1
- 101100481406 Mus musculus Tie1 gene Proteins 0.000 description 1
- 102100026933 Myelin-associated neurite-outgrowth inhibitor Human genes 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-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
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 1
- 108030005449 Polo kinases Proteins 0.000 description 1
- 102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 description 1
- 108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 description 1
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 description 1
- 102000005765 Proto-Oncogene Proteins c-akt Human genes 0.000 description 1
- 102100039889 Pyrin domain-containing protein 5 Human genes 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 102100031462 Serine/threonine-protein kinase PLK2 Human genes 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 230000017274 T cell anergy Effects 0.000 description 1
- 230000005867 T cell response Effects 0.000 description 1
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 1
- 102000013530 TOR Serine-Threonine Kinases Human genes 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
- 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
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- 241000863480 Vinca Species 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 229930013930 alkaloid Natural products 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
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
- 235000012501 ammonium carbonate Nutrition 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 description 1
- 229960001220 amsacrine Drugs 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940124650 anti-cancer therapies Drugs 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000003432 anti-folate effect Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 230000002137 anti-vascular effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000012635 anticancer drug combination Substances 0.000 description 1
- 238000011319 anticancer therapy Methods 0.000 description 1
- 238000011394 anticancer treatment Methods 0.000 description 1
- 229940127074 antifolate Drugs 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 239000003080 antimitotic agent Substances 0.000 description 1
- 229940045719 antineoplastic alkylating agent nitrosoureas Drugs 0.000 description 1
- 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 description 1
- FZCSTZYAHCUGEM-UHFFFAOYSA-N aspergillomarasmine B Natural products OC(=O)CNC(C(O)=O)CNC(C(O)=O)CC(O)=O FZCSTZYAHCUGEM-UHFFFAOYSA-N 0.000 description 1
- 230000035578 autophosphorylation Effects 0.000 description 1
- 229960003005 axitinib Drugs 0.000 description 1
- RITAVMQDGBJQJZ-FMIVXFBMSA-N axitinib Chemical compound CNC(=O)C1=CC=CC=C1SC1=CC=C(C(\C=C\C=2N=CC=CC=2)=NN2)C2=C1 RITAVMQDGBJQJZ-FMIVXFBMSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229960000397 bevacizumab Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 238000002725 brachytherapy Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 201000008274 breast adenocarcinoma Diseases 0.000 description 1
- 229960002092 busulfan Drugs 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
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 229960002412 cediranib Drugs 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000012820 cell cycle checkpoint Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000004637 cellular stress Effects 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 229960000640 dactinomycin Drugs 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
- 210000004443 dendritic cell Anatomy 0.000 description 1
- CFCUWKMKBJTWLW-UHFFFAOYSA-N deoliosyl-3C-alpha-L-digitoxosyl-MTM Natural products CC=1C(O)=C2C(O)=C3C(=O)C(OC4OC(C)C(O)C(OC5OC(C)C(O)C(OC6OC(C)C(O)C(C)(O)C6)C5)C4)C(C(OC)C(=O)C(O)C(C)O)CC3=CC2=CC=1OC(OC(C)C1O)CC1OC1CC(O)C(O)C(C)O1 CFCUWKMKBJTWLW-UHFFFAOYSA-N 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 125000004431 deuterium atom Chemical group 0.000 description 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Substances ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 102000015694 estrogen receptors Human genes 0.000 description 1
- 108010038795 estrogen receptors Proteins 0.000 description 1
- MVUMJYQUKKUOHO-AATRIKPKSA-N ethyl (e)-3-(dimethylamino)prop-2-enoate Chemical compound CCOC(=O)\C=C\N(C)C MVUMJYQUKKUOHO-AATRIKPKSA-N 0.000 description 1
- 235000019439 ethyl acetate Nutrition 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 238000002710 external beam radiation therapy Methods 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 150000005699 fluoropyrimidines Chemical class 0.000 description 1
- 239000004052 folic acid antagonist Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000001033 granulometry Methods 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 210000003917 human chromosome Anatomy 0.000 description 1
- 210000004293 human mammary gland Anatomy 0.000 description 1
- 229960001330 hydroxycarbamide Drugs 0.000 description 1
- 229960001001 ibritumomab tiuxetan Drugs 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000001024 immunotherapeutic effect Effects 0.000 description 1
- 230000002637 immunotoxin Effects 0.000 description 1
- 229940051026 immunotoxin Drugs 0.000 description 1
- 231100000608 immunotoxin Toxicity 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 229940028885 interleukin-4 Drugs 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 230000005865 ionizing radiation Effects 0.000 description 1
- 229960005386 ipilimumab Drugs 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000008263 liquid aerosol Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- RDPLOLUNEKBWBR-UHFFFAOYSA-L magnesium;sodium;sulfate Chemical compound [Na+].[Mg+2].[O-]S([O-])(=O)=O RDPLOLUNEKBWBR-UHFFFAOYSA-L 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N methyl tert-butyl ether Substances COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 1
- 229910021421 monocrystalline silicon Inorganic materials 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 230000009437 off-target effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229960000639 pazopanib Drugs 0.000 description 1
- CUIHSIWYWATEQL-UHFFFAOYSA-N pazopanib Chemical compound C1=CC2=C(C)N(C)N=C2C=C1N(C)C(N=1)=CC=NC=1NC1=CC=C(C)C(S(N)(=O)=O)=C1 CUIHSIWYWATEQL-UHFFFAOYSA-N 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000008823 permeabilization Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 150000003905 phosphatidylinositols Chemical class 0.000 description 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
- 229960003171 plicamycin Drugs 0.000 description 1
- 235000008476 powdered milk Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000004237 preparative chromatography Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000009862 primary prevention Effects 0.000 description 1
- 230000007757 pro-survival signaling Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 102000003998 progesterone receptors Human genes 0.000 description 1
- 108090000468 progesterone receptors Proteins 0.000 description 1
- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
- 239000003909 protein kinase inhibitor Substances 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 239000013014 purified material Substances 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- DJXNJVFEFSWHLY-UHFFFAOYSA-N quinoline-3-carboxylic acid Chemical compound C1=CC=CC2=CC(C(=O)O)=CN=C21 DJXNJVFEFSWHLY-UHFFFAOYSA-N 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 229960004432 raltitrexed Drugs 0.000 description 1
- 229940124617 receptor tyrosine kinase inhibitor Drugs 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 210000003289 regulatory T cell Anatomy 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- OAKGNIRUXAZDQF-TXHRRWQRSA-N retaspimycin 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(O)C1=CC(O)=C2NCC=C OAKGNIRUXAZDQF-TXHRRWQRSA-N 0.000 description 1
- 229950002836 retaspimycin Drugs 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 229960004641 rituximab Drugs 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 230000009863 secondary prevention Effects 0.000 description 1
- 230000008054 signal transmission Effects 0.000 description 1
- 230000009131 signaling function Effects 0.000 description 1
- 230000003007 single stranded DNA break Effects 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 230000005783 single-strand break Effects 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 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 1
- 239000011775 sodium fluoride Substances 0.000 description 1
- 235000013024 sodium fluoride Nutrition 0.000 description 1
- 229940048086 sodium pyrophosphate Drugs 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 229960003787 sorafenib Drugs 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000003335 steric effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000012089 stop solution Substances 0.000 description 1
- 230000009221 stress response pathway Effects 0.000 description 1
- CIOAGBVUUVVLOB-OUBTZVSYSA-N strontium-89 Chemical compound [89Sr] CIOAGBVUUVVLOB-OUBTZVSYSA-N 0.000 description 1
- 229940006509 strontium-89 Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229960001796 sunitinib Drugs 0.000 description 1
- WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic 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
- 229950007866 tanespimycin Drugs 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 229940063683 taxotere 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
- 229960001674 tegafur Drugs 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
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- KGYLMXMMQNTWEM-UHFFFAOYSA-J tetrachloropalladium Chemical compound Cl[Pd](Cl)(Cl)Cl KGYLMXMMQNTWEM-UHFFFAOYSA-J 0.000 description 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 1
- 235000019818 tetrasodium diphosphate Nutrition 0.000 description 1
- 239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- 229960005267 tositumomab Drugs 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 229950007217 tremelimumab Drugs 0.000 description 1
- 150000004684 trihydrates Chemical class 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
- 230000004614 tumor growth Effects 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 229960000241 vandetanib Drugs 0.000 description 1
- UHTHHESEBZOYNR-UHFFFAOYSA-N vandetanib Chemical compound COC1=CC(C(/N=CN2)=N/C=3C(=CC(Br)=CC=3)F)=C2C=C1OCC1CCN(C)CC1 UHTHHESEBZOYNR-UHFFFAOYSA-N 0.000 description 1
- 229950000578 vatalanib Drugs 0.000 description 1
- YCOYDOIWSSHVCK-UHFFFAOYSA-N vatalanib Chemical compound C1=CC(Cl)=CC=C1NC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 YCOYDOIWSSHVCK-UHFFFAOYSA-N 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- 239000012224 working solution Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762472080P | 2017-03-16 | 2017-03-16 | |
| PCT/EP2018/056516 WO2018167203A1 (en) | 2017-03-16 | 2018-03-15 | Deuterated imidazo[4,5-c]quinolin-2-one compounds and their use in treating cancer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA124554C2 true UA124554C2 (uk) | 2021-10-05 |
Family
ID=61801891
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UAA201910213A UA124554C2 (uk) | 2017-03-16 | 2018-03-15 | ДЕЙТЕРОВАНІ СПОЛУКИ ІМІДАЗО[4,5-c]ХІНОЛІН-2-ОНУ ТА ЇХ ЗАСТОСУВАННЯ В ЛІКУВАННІ РАКУ |
Country Status (25)
| Country | Link |
|---|---|
| US (2) | US20200087300A1 (enExample) |
| EP (1) | EP3596076A1 (enExample) |
| JP (1) | JP2020514344A (enExample) |
| KR (1) | KR20190129923A (enExample) |
| CN (1) | CN110431139B (enExample) |
| AU (1) | AU2018234985B2 (enExample) |
| BR (1) | BR112019018723A2 (enExample) |
| CA (1) | CA3055258A1 (enExample) |
| CL (1) | CL2019002527A1 (enExample) |
| CO (1) | CO2019010029A2 (enExample) |
| CR (1) | CR20190429A (enExample) |
| DO (1) | DOP2019000228A (enExample) |
| EA (1) | EA038233B1 (enExample) |
| EC (1) | ECSP19066134A (enExample) |
| IL (1) | IL269272A (enExample) |
| JO (1) | JOP20190209A1 (enExample) |
| MA (1) | MA49884A (enExample) |
| MX (1) | MX2019010898A (enExample) |
| NI (1) | NI201900094A (enExample) |
| PE (1) | PE20191486A1 (enExample) |
| PH (1) | PH12019502086A1 (enExample) |
| SG (1) | SG11201908065YA (enExample) |
| TW (1) | TW201843151A (enExample) |
| UA (1) | UA124554C2 (enExample) |
| WO (1) | WO2018167203A1 (enExample) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| LV15575A (lv) * | 2019-12-20 | 2021-06-20 | Latvijas Organiskās Sintēzes Institūts | Selenofēnhromēnu deiterēti analogi, to iegūšana un izmantošana |
| CN116194109A (zh) | 2020-06-24 | 2023-05-30 | 阿斯利康(英国)有限公司 | 抗体-药物缀合物和atm抑制剂的组合 |
| CN116056698B (zh) * | 2020-09-21 | 2024-11-19 | 威尚（上海）生物医药有限公司 | 具有血脑屏障穿透能力的取代的1-(3,3-二氟哌啶-4-基)-咪唑并[4,5-c]喹啉-2-酮化合物 |
| EP3992191A1 (en) | 2020-11-03 | 2022-05-04 | Deutsches Krebsforschungszentrum | Imidazo[4,5-c]quinoline compounds and their use as atm kinase inhibitors |
| WO2022128833A1 (en) | 2020-12-15 | 2022-06-23 | Merck Patent Gmbh | Solid transition metal-ligand complexes |
| CN118434736A (zh) * | 2022-01-26 | 2024-08-02 | 正大天晴药业集团股份有限公司 | 含有肼基的化合物 |
| WO2026120558A1 (en) | 2024-12-06 | 2026-06-11 | Sun Pharma Advanced Research Company Limited | Macrocyclic compounds as atm inhibitors |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6221335B1 (en) * | 1994-03-25 | 2001-04-24 | Isotechnika, Inc. | Method of using deuterated calcium channel blockers |
| GB9624482D0 (en) | 1995-12-18 | 1997-01-15 | Zeneca Phaema S A | Chemical compounds |
| CA2242425C (en) | 1996-02-13 | 2006-07-18 | Zeneca Limited | Quinazoline derivatives as vegf inhibitors |
| NZ331191A (en) | 1996-03-05 | 2000-03-27 | Zeneca Ltd | 4-anilinoquinazoline derivatives and pharmaceutical compositions thereof |
| GB9718972D0 (en) | 1996-09-25 | 1997-11-12 | Zeneca Ltd | Chemical compounds |
| US20090082387A1 (en) * | 2007-09-26 | 2009-03-26 | Protia, Llc | Deuterium-enriched nvp-bez234 |
| MA33332B1 (fr) * | 2009-06-04 | 2012-06-01 | Novartis Ag | Dérivés de la 1h-imidazo[4,5-c]quinolinone |
| CN102372711B (zh) * | 2010-08-18 | 2014-09-17 | 山东轩竹医药科技有限公司 | 咪唑并喹啉类PI3K和mTOR双重抑制剂 |
| CN102399218A (zh) | 2010-09-16 | 2012-04-04 | 和记黄埔医药（上海）有限公司 | 一类并合三杂环及其作为pi3k抑制剂的用途 |
| NO2714752T3 (enExample) * | 2014-05-08 | 2018-04-21 | ||
| PL3277681T3 (pl) * | 2015-04-02 | 2019-10-31 | Merck Patent Gmbh | Imidazolonylochinoliny i ich zastosowanie jako inhibitorów kinazy atm |
| GB201516504D0 (en) * | 2015-09-17 | 2015-11-04 | Astrazeneca Ab | Imadazo(4,5-c)quinolin-2-one Compounds and their use in treating cancer |
-
2017
- 2017-06-16 JO JOP/2019/0209A patent/JOP20190209A1/ar unknown
-
2018
- 2018-03-15 KR KR1020197030079A patent/KR20190129923A/ko not_active Abandoned
- 2018-03-15 MX MX2019010898A patent/MX2019010898A/es unknown
- 2018-03-15 TW TW107108833A patent/TW201843151A/zh unknown
- 2018-03-15 SG SG11201908065YA patent/SG11201908065YA/en unknown
- 2018-03-15 WO PCT/EP2018/056516 patent/WO2018167203A1/en not_active Ceased
- 2018-03-15 CR CR20190429A patent/CR20190429A/es unknown
- 2018-03-15 CN CN201880017916.4A patent/CN110431139B/zh active Active
- 2018-03-15 BR BR112019018723A patent/BR112019018723A2/pt not_active Application Discontinuation
- 2018-03-15 UA UAA201910213A patent/UA124554C2/uk unknown
- 2018-03-15 EA EA201992090A patent/EA038233B1/ru unknown
- 2018-03-15 MA MA049884A patent/MA49884A/fr unknown
- 2018-03-15 US US16/493,850 patent/US20200087300A1/en not_active Abandoned
- 2018-03-15 CA CA3055258A patent/CA3055258A1/en not_active Abandoned
- 2018-03-15 JP JP2019549446A patent/JP2020514344A/ja not_active Ceased
- 2018-03-15 AU AU2018234985A patent/AU2018234985B2/en not_active Ceased
- 2018-03-15 EP EP18713818.5A patent/EP3596076A1/en not_active Withdrawn
- 2018-03-15 PE PE2019001872A patent/PE20191486A1/es unknown
-
2019
- 2019-09-03 CL CL2019002527A patent/CL2019002527A1/es unknown
- 2019-09-06 DO DO2019000228A patent/DOP2019000228A/es unknown
- 2019-09-11 IL IL26927219A patent/IL269272A/en unknown
- 2019-09-12 EC ECSENADI201966134A patent/ECSP19066134A/es unknown
- 2019-09-13 NI NI201900094A patent/NI201900094A/es unknown
- 2019-09-13 PH PH12019502086A patent/PH12019502086A1/en unknown
- 2019-09-16 CO CONC2019/0010029A patent/CO2019010029A2/es unknown
-
2021
- 2021-07-20 US US17/380,323 patent/US20210347775A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| ECSP19066134A (es) | 2019-09-30 |
| AU2018234985A1 (en) | 2019-10-24 |
| CA3055258A1 (en) | 2018-09-20 |
| CN110431139A (zh) | 2019-11-08 |
| CL2019002527A1 (es) | 2019-11-22 |
| SG11201908065YA (en) | 2019-09-27 |
| EA201992090A1 (ru) | 2020-03-06 |
| EA038233B1 (ru) | 2021-07-28 |
| CO2019010029A2 (es) | 2019-09-30 |
| US20200087300A1 (en) | 2020-03-19 |
| WO2018167203A1 (en) | 2018-09-20 |
| TW201843151A (zh) | 2018-12-16 |
| KR20190129923A (ko) | 2019-11-20 |
| PH12019502086A1 (en) | 2020-03-09 |
| PE20191486A1 (es) | 2019-10-18 |
| AU2018234985B2 (en) | 2020-04-02 |
| CN110431139B (zh) | 2022-07-05 |
| CR20190429A (es) | 2019-11-12 |
| EP3596076A1 (en) | 2020-01-22 |
| MX2019010898A (es) | 2019-11-07 |
| BR112019018723A2 (pt) | 2020-04-07 |
| JOP20190209A1 (ar) | 2019-09-12 |
| IL269272A (en) | 2019-11-28 |
| NI201900094A (es) | 2020-03-18 |
| MA49884A (fr) | 2020-06-24 |
| US20210347775A1 (en) | 2021-11-11 |
| JP2020514344A (ja) | 2020-05-21 |
| DOP2019000228A (es) | 2019-09-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US12310968B2 (en) | Chiral diaryl macrocycles and uses thereof | |
| RU2701193C2 (ru) | Арилхиназолины | |
| ES2853924T3 (es) | Derivados de 8-[6-[3-(amino)propoxi]-3-piridil]1-isopropilimidazo[4,5-c]quinolin-2-ona como moduladores selectivos de la cinasa de la ataxia telangiectasia mutada (atm) para el tratamiento del cáncer | |
| AU2018234985B2 (en) | Deuterated imidazo[4,5-c]quinolin-2-one compounds and their use in treating cancer | |
| WO2014143601A1 (en) | CDC7 Inhibitors | |
| WO2016044772A1 (en) | Combination therapies for treatment of cancer | |
| AU2011312485A1 (en) | Crystalline (R) - (E) -2- (4- (2- (5- (1- (3, 5 -dichloropyridin-4 -yl) ethoxy) - 1H - indazol - 3 - yl) vinyl) -1 H- pyrazol- 1 -yl) ethanol and its use as FGFR inhibitor | |
| US12583855B2 (en) | RET selective inhibitor, preparation method therefor and use thereof | |
| EA022163B1 (ru) | ДВОЙНЫЕ ИНГИБИТОРЫ PI3 КИНАЗЫ/mTOR | |
| US20220265656A1 (en) | Combination therapies with ire1 small molecule inhibitors | |
| CN108026046B (zh) | 取代的喹唑啉化合物及其作为g12c突变体kras、hras和/或nras蛋白质的抑制剂的用途 | |
| WO2019057757A1 (en) | 1,3-DIHYDROIMIDAZO [4,5-C] CINNOLIN-2-ONE COMPOUNDS AND THEIR USE IN THE TREATMENT OF CANCER | |
| TW201808939A (zh) | <img align="absmiddle" height="18px" width="27px" file="d10999.TIF" alt="其他非圖式 ed10999.png" img-content="tif" orientation="portrait" inline="yes" giffile="ed10999.png"></img>啉-4-胺化合物及其在治療癌症中之用途 | |
| CN107501279B (zh) | 呋喃并喹啉二酮类化合物及其医药用途 | |
| CA3015953A1 (en) | N,n-dimethyl-3-[[5-(3-methyl-2-oxo-1-tetrahydropyran-4-yl-imidazo[4,5-c]quinolin-8-yl)-2-pyridyl]oxy]propan-1-amine oxide as atm (ataxia telangiectasia mutated) kinase modulator for treating cancer | |
| HK40016607A (en) | Deuterated imidazo[4,5-c]quinolin-2-one compounds and their use in treating cancer | |
| BR112016025153B1 (pt) | "compostos de imidazo[4,5-c]quinolin-2-ona, composição farmaceutica e seu uso no tratamento de câncer |