JP2016540773A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2016540773A5 JP2016540773A5 JP2016536710A JP2016536710A JP2016540773A5 JP 2016540773 A5 JP2016540773 A5 JP 2016540773A5 JP 2016536710 A JP2016536710 A JP 2016536710A JP 2016536710 A JP2016536710 A JP 2016536710A JP 2016540773 A5 JP2016540773 A5 JP 2016540773A5
- Authority
- JP
- Japan
- Prior art keywords
- composition
- cancer
- compound
- pharmaceutically acceptable
- acceptable salt
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 150000001875 compounds Chemical class 0.000 claims description 148
- 239000000203 mixture Substances 0.000 claims description 130
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 73
- 201000011510 cancer Diseases 0.000 claims description 56
- 150000003839 salts Chemical class 0.000 claims description 56
- 239000011780 sodium chloride Substances 0.000 claims description 56
- 210000004027 cells Anatomy 0.000 claims description 54
- 239000000651 prodrug Substances 0.000 claims description 51
- 229940002612 prodrugs Drugs 0.000 claims description 51
- 125000001931 aliphatic group Chemical group 0.000 claims description 46
- 125000005842 heteroatoms Chemical group 0.000 claims description 38
- 229910052757 nitrogen Inorganic materials 0.000 claims description 38
- NINIDFKCEFEMDL-UHFFFAOYSA-N sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 38
- 229910052717 sulfur Chemical group 0.000 claims description 38
- 239000011593 sulfur Chemical group 0.000 claims description 38
- 229910052760 oxygen Inorganic materials 0.000 claims description 37
- MYMOFIZGZYHOMD-UHFFFAOYSA-N oxygen Chemical group O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 37
- 239000001301 oxygen Substances 0.000 claims description 37
- 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 claims description 33
- 229960005277 gemcitabine Drugs 0.000 claims description 33
- 230000002401 inhibitory effect Effects 0.000 claims description 29
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 28
- 208000008443 Pancreatic Carcinoma Diseases 0.000 claims description 26
- 201000002528 pancreatic cancer Diseases 0.000 claims description 26
- 229920003013 deoxyribonucleic acid Polymers 0.000 claims description 24
- 125000005843 halogen group Chemical group 0.000 claims description 24
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 24
- 239000003112 inhibitor Substances 0.000 claims description 23
- 125000004429 atoms Chemical group 0.000 claims description 21
- 239000003814 drug Substances 0.000 claims description 21
- 229960004316 cisplatin Drugs 0.000 claims description 19
- 238000000034 method Methods 0.000 claims description 19
- LXZZYRPGZAFOLE-UHFFFAOYSA-L transplatin Chemical compound [H][N]([H])([H])[Pt](Cl)(Cl)[N]([H])([H])[H] LXZZYRPGZAFOLE-UHFFFAOYSA-L 0.000 claims description 19
- 208000009956 Adenocarcinoma Diseases 0.000 claims description 18
- 108009000276 Base Excision Repair Proteins 0.000 claims description 16
- 206010028980 Neoplasm Diseases 0.000 claims description 16
- 230000033590 base-excision repair Effects 0.000 claims description 16
- 102000004169 proteins and genes Human genes 0.000 claims description 16
- 108090000623 proteins and genes Proteins 0.000 claims description 16
- 229960005420 Etoposide Drugs 0.000 claims description 14
- VJJPUSNTGOMMGY-MRVIYFEKSA-N Etoposide Chemical group 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 14
- 206010025323 Lymphomas Diseases 0.000 claims description 14
- 206010039491 Sarcoma Diseases 0.000 claims description 14
- 229910052697 platinum Inorganic materials 0.000 claims description 14
- 229960004562 Carboplatin Drugs 0.000 claims description 12
- 101700027219 LIG3 Proteins 0.000 claims description 12
- 102100012451 LIG3 Human genes 0.000 claims description 12
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 12
- 208000002154 Non-Small-Cell Lung Carcinoma Diseases 0.000 claims description 12
- 206010025310 Other lymphomas Diseases 0.000 claims description 12
- 102100014579 PARP1 Human genes 0.000 claims description 12
- 101700053624 PARP2 Proteins 0.000 claims description 12
- 102100017733 PARP2 Human genes 0.000 claims description 12
- 108010064218 Poly (ADP-Ribose) Polymerase-1 Proteins 0.000 claims description 12
- DVQHYTBCTGYNNN-UHFFFAOYSA-N azane;cyclobutane-1,1-dicarboxylic acid;platinum Chemical compound N.N.[Pt].OC(=O)C1(C(O)=O)CCC1 DVQHYTBCTGYNNN-UHFFFAOYSA-N 0.000 claims description 12
- 201000005202 lung cancer Diseases 0.000 claims description 12
- 238000001959 radiotherapy Methods 0.000 claims description 12
- 108009000071 Non-small cell lung cancer Proteins 0.000 claims description 10
- 206010041823 Squamous cell carcinoma Diseases 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 239000002168 alkylating agent Substances 0.000 claims description 10
- 230000000340 anti-metabolite Effects 0.000 claims description 10
- 239000002256 antimetabolite Substances 0.000 claims description 10
- VSJKWCGYPAHWDS-FQEVSTJZSA-N Camptothecin Chemical group C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 claims description 8
- 102100005767 LIG1 Human genes 0.000 claims description 8
- 101700041876 LRIG3 Proteins 0.000 claims description 8
- 206010024612 Lipoma Diseases 0.000 claims description 8
- 101700061424 POLB Proteins 0.000 claims description 8
- 201000009030 carcinoma Diseases 0.000 claims description 8
- 238000002512 chemotherapy Methods 0.000 claims description 8
- 125000004122 cyclic group Chemical group 0.000 claims description 8
- 230000000694 effects Effects 0.000 claims description 8
- 201000011066 hemangioma Diseases 0.000 claims description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 125000006574 non-aromatic ring group Chemical group 0.000 claims description 8
- 238000009472 formulation Methods 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 102100000648 ATM Human genes 0.000 claims description 6
- 108060006202 ATM Proteins 0.000 claims description 6
- 206010016629 Fibroma Diseases 0.000 claims description 6
- MDOJTZQKHMAPBK-UHFFFAOYSA-N Iniparib Chemical compound NC(=O)C1=CC=C(I)C([N+]([O-])=O)=C1 MDOJTZQKHMAPBK-UHFFFAOYSA-N 0.000 claims description 6
- 210000000214 Mouth Anatomy 0.000 claims description 6
- 208000000587 Small Cell Lung Carcinoma Diseases 0.000 claims description 6
- 206010041067 Small cell lung cancer Diseases 0.000 claims description 6
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temodal Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 claims description 6
- 150000008052 alkyl sulfonates Chemical class 0.000 claims description 6
- 230000003115 biocidal Effects 0.000 claims description 6
- 239000012472 biological sample Substances 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 201000008808 fibrosarcoma Diseases 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 230000003211 malignant Effects 0.000 claims description 6
- 201000009410 rhabdomyosarcoma Diseases 0.000 claims description 6
- 230000001235 sensitizing Effects 0.000 claims description 6
- 231100000202 sensitizing Toxicity 0.000 claims description 6
- 229960004964 temozolomide Drugs 0.000 claims description 6
- 125000003566 oxetanyl group Chemical group 0.000 claims description 5
- ZROHGHOFXNOHSO-BNTLRKBRSA-L (1R,2R)-cyclohexane-1,2-diamine;oxalate;platinum(2+) Chemical compound [H][N]([C@@H]1CCCC[C@H]1[N]1([H])[H])([H])[Pt]11OC(=O)C(=O)O1 ZROHGHOFXNOHSO-BNTLRKBRSA-L 0.000 claims description 4
- GHASVSINZRGABV-UHFFFAOYSA-N 5-flurouricil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 4
- 210000000988 Bone and Bones Anatomy 0.000 claims description 4
- 206010006187 Breast cancer Diseases 0.000 claims description 4
- 102100019698 CHEK2 Human genes 0.000 claims description 4
- 108060006647 CHEK2 Proteins 0.000 claims description 4
- 210000000845 Cartilage Anatomy 0.000 claims description 4
- HAWPXGHAZFHHAD-UHFFFAOYSA-N Chlormethine Chemical group ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 claims description 4
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 claims description 4
- 210000001072 Colon Anatomy 0.000 claims description 4
- 229960000684 Cytarabine Drugs 0.000 claims description 4
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytosar 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 claims description 4
- STQGQHZAVUOBTE-VGBVRHCVSA-N DAUNOMYCIN 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 claims description 4
- 231100000277 DNA damage Toxicity 0.000 claims description 4
- 102000020346 DNA glycosylase family Human genes 0.000 claims description 4
- 108020001738 DNA glycosylase family Proteins 0.000 claims description 4
- 102000008422 EC 2.7.1.78 Human genes 0.000 claims description 4
- 108010021757 EC 2.7.1.78 Proteins 0.000 claims description 4
- 102000010719 EC 4.2.99.18 Human genes 0.000 claims description 4
- 108010063362 EC 4.2.99.18 Proteins 0.000 claims description 4
- 108010042407 Endonucleases Proteins 0.000 claims description 4
- 108060009526 FEN1 Proteins 0.000 claims description 4
- 102100018058 FEN1 Human genes 0.000 claims description 4
- 229960002949 Fluorouracil Drugs 0.000 claims description 4
- 206010018338 Glioma Diseases 0.000 claims description 4
- 101700085012 H2AX Proteins 0.000 claims description 4
- 102100013495 H2AX Human genes 0.000 claims description 4
- 208000002927 Hamartoma Diseases 0.000 claims description 4
- 208000001258 Hemangiosarcoma Diseases 0.000 claims description 4
- 206010073071 Hepatocellular carcinoma Diseases 0.000 claims description 4
- 206010021143 Hypoxia Diseases 0.000 claims description 4
- 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 4
- 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 claims description 4
- 101710006797 LIG1 Proteins 0.000 claims description 4
- 102100005410 LINE-1 retrotransposable element ORF2 protein Human genes 0.000 claims description 4
- 206010024190 Leiomyosarcomas Diseases 0.000 claims description 4
- 102100008690 MBD4 Human genes 0.000 claims description 4
- 101700060039 MBD4 Proteins 0.000 claims description 4
- 102100009282 MCPH1 Human genes 0.000 claims description 4
- 101700070231 MCPH1 Proteins 0.000 claims description 4
- 102100002907 MDC1 Human genes 0.000 claims description 4
- 101700021563 MDC1 Proteins 0.000 claims description 4
- 102100017079 MPG Human genes 0.000 claims description 4
- 101710007617 MPG Proteins 0.000 claims description 4
- 101700084879 MRE11 Proteins 0.000 claims description 4
- 102100014041 MRE11 Human genes 0.000 claims description 4
- 102100003827 MUTYH Human genes 0.000 claims description 4
- 101700053678 MUTYH Proteins 0.000 claims description 4
- 206010025650 Malignant melanoma Diseases 0.000 claims description 4
- 229960004961 Mechlorethamine Drugs 0.000 claims description 4
- 206010027191 Meningioma Diseases 0.000 claims description 4
- 101700015287 NBN Proteins 0.000 claims description 4
- 102100017313 NBN Human genes 0.000 claims description 4
- 101700076947 NBS1 Proteins 0.000 claims description 4
- 101700012596 NEIL1 Proteins 0.000 claims description 4
- 102100002714 NEIL1 Human genes 0.000 claims description 4
- 101700036395 NEIL2 Proteins 0.000 claims description 4
- 102100018379 NEIL2 Human genes 0.000 claims description 4
- 101700052800 NEIL3 Proteins 0.000 claims description 4
- 102100018378 NEIL3 Human genes 0.000 claims description 4
- 101710044526 NLRP2 Proteins 0.000 claims description 4
- 101710040088 NTG1 Proteins 0.000 claims description 4
- 101700063313 NTH2 Proteins 0.000 claims description 4
- 102100015692 NTHL1 Human genes 0.000 claims description 4
- 101710026674 NTHL1 Proteins 0.000 claims description 4
- 229950007221 Nedaplatin Drugs 0.000 claims description 4
- 101700055476 OGG1 Proteins 0.000 claims description 4
- 102100001092 OGG1 Human genes 0.000 claims description 4
- 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 4
- 206010033128 Ovarian cancer Diseases 0.000 claims description 4
- 101710013972 PLSCR1 Proteins 0.000 claims description 4
- 101700012117 POLG Proteins 0.000 claims description 4
- 101710006355 PPP1R13L Proteins 0.000 claims description 4
- 102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 claims description 4
- 108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 claims description 4
- CPTBDICYNRMXFX-UHFFFAOYSA-N Procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 claims description 4
- 102100016116 RAD50 Human genes 0.000 claims description 4
- 108060007644 RAD50 Proteins 0.000 claims description 4
- 210000000664 Rectum Anatomy 0.000 claims description 4
- 108060009199 SMUG1 Proteins 0.000 claims description 4
- 102100000668 SMUG1 Human genes 0.000 claims description 4
- 102100005497 TDG Human genes 0.000 claims description 4
- 101700031622 TDG Proteins 0.000 claims description 4
- 102100019730 TP53 Human genes 0.000 claims description 4
- 101710026335 TP53 Proteins 0.000 claims description 4
- 101700053112 TREH Proteins 0.000 claims description 4
- 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 4
- 102000000504 Tumor Suppressor p53-Binding Protein 1 Human genes 0.000 claims description 4
- 108010041385 Tumor Suppressor p53-Binding Protein 1 Proteins 0.000 claims description 4
- 102100005744 UNG Human genes 0.000 claims description 4
- 108060009204 UNG Proteins 0.000 claims description 4
- 208000008383 Wilms Tumor Diseases 0.000 claims description 4
- 108010000443 X-ray Repair Cross Complementing Protein 1 Proteins 0.000 claims description 4
- 102000002258 X-ray Repair Cross Complementing Protein 1 Human genes 0.000 claims description 4
- 201000003076 angiosarcoma Diseases 0.000 claims description 4
- KLNFSAOEKUDMFA-UHFFFAOYSA-N azanide;2-hydroxyacetic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OCC(O)=O KLNFSAOEKUDMFA-UHFFFAOYSA-N 0.000 claims description 4
- 125000002393 azetidinyl group Chemical group 0.000 claims description 4
- 229960002436 cladribine Drugs 0.000 claims description 4
- 239000002552 dosage form Substances 0.000 claims description 4
- 201000011523 endocrine gland cancer Diseases 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- 229960000390 fludarabine Drugs 0.000 claims description 4
- 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 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 201000010536 head and neck cancer Diseases 0.000 claims description 4
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 4
- 229960001330 hydroxycarbamide Drugs 0.000 claims description 4
- VSNHCAURESNICA-UHFFFAOYSA-N hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 claims description 4
- 229940027318 hydroxyurea Drugs 0.000 claims description 4
- 230000001146 hypoxic Effects 0.000 claims description 4
- 229960004768 irinotecan Drugs 0.000 claims description 4
- 201000010260 leiomyoma Diseases 0.000 claims description 4
- 230000036244 malformation Effects 0.000 claims description 4
- 201000001441 melanoma Diseases 0.000 claims description 4
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 claims description 4
- 229960001428 mercaptopurine Drugs 0.000 claims description 4
- 229960000485 methotrexate Drugs 0.000 claims description 4
- 235000013919 monopotassium glutamate Nutrition 0.000 claims description 4
- 201000008026 nephroblastoma Diseases 0.000 claims description 4
- 201000004404 neurofibroma Diseases 0.000 claims description 4
- 229960000572 olaparib Drugs 0.000 claims description 4
- 201000008968 osteosarcoma Diseases 0.000 claims description 4
- 229960001756 oxaliplatin Drugs 0.000 claims description 4
- 229960005079 pemetrexed Drugs 0.000 claims description 4
- WBXPDJSOTKVWSJ-ZDUSSCGKSA-N pemetrexed Chemical compound C=1NC=2NC(N)=NC(=O)C=2C=1CCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 WBXPDJSOTKVWSJ-ZDUSSCGKSA-N 0.000 claims description 4
- 125000004193 piperazinyl group Chemical group 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- 229960000624 procarbazine Drugs 0.000 claims description 4
- 238000007363 ring formation reaction Methods 0.000 claims description 4
- CKNPWBAXEKSCRG-UHFFFAOYSA-J satraplatin Chemical compound CC(=O)O[Pt-2]([NH3+])(Cl)(Cl)(OC(C)=O)[NH2+]C1CCCCC1 CKNPWBAXEKSCRG-UHFFFAOYSA-J 0.000 claims description 4
- 229960005399 satraplatin Drugs 0.000 claims description 4
- WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 claims description 4
- 229960000303 topotecan Drugs 0.000 claims description 4
- 108060008633 trl1 Proteins 0.000 claims description 4
- -1 1,4-thiazepanyl Chemical group 0.000 claims description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- NRUKOCRGYNPUPR-QBPJDGROSA-N (5S,5aR,8aR,9R)-5-[[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-thiophen-2-yl-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](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 claims description 2
- OMJKFYKNWZZKTK-POHAHGRESA-N (5Z)-5-(dimethylaminohydrazinylidene)imidazole-4-carboxamide Chemical compound CN(C)N\N=C1/N=CN=C1C(N)=O OMJKFYKNWZZKTK-POHAHGRESA-N 0.000 claims description 2
- KMSKQZKKOZQFFG-YXRRJAAWSA-N (7S,9S)-7-[(2R,4S,5S,6S)-4-amino-6-methyl-5-[(2R)-oxan-2-yl]oxyoxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione 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-YXRRJAAWSA-N 0.000 claims description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- COVZYZSDYWQREU-UHFFFAOYSA-N 1,4-Butanediol, dimethanesulfonate Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 claims description 2
- 125000005960 1,4-diazepanyl group Chemical group 0.000 claims description 2
- 125000005962 1,4-oxazepanyl group Chemical group 0.000 claims description 2
- PCHKPVIQAHNQLW-CQSZACIVSA-N 2-[4-[(3S)-piperidin-3-yl]phenyl]indazole-7-carboxamide Chemical compound N1=C2C(C(=O)N)=CC=CC2=CN1C(C=C1)=CC=C1[C@@H]1CCCNC1 PCHKPVIQAHNQLW-CQSZACIVSA-N 0.000 claims description 2
- GSCPDZHWVNUUFI-UHFFFAOYSA-N 3-Aminobenzamide Chemical compound NC(=O)C1=CC=CC(N)=C1 GSCPDZHWVNUUFI-UHFFFAOYSA-N 0.000 claims description 2
- 125000001845 4 membered carbocyclic group Chemical group 0.000 claims description 2
- HYNBNUYQTQIHJK-UHFFFAOYSA-N 4-[[4-fluoro-3-(4-methoxypiperidine-1-carbonyl)phenyl]methyl]-2H-phthalazin-1-one Chemical compound C1CC(OC)CCN1C(=O)C1=CC(CC=2C3=CC=CC=C3C(=O)NN=2)=CC=C1F HYNBNUYQTQIHJK-UHFFFAOYSA-N 0.000 claims description 2
- TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical group 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 claims description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N ADRIAMYCIN 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 2
- 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 2
- 229960004176 Aclarubicin Drugs 0.000 claims description 2
- 206010001233 Adenoma benign Diseases 0.000 claims description 2
- 210000004100 Adrenal Glands Anatomy 0.000 claims description 2
- UUVWYPNAQBNQJQ-UHFFFAOYSA-N Altretamine Chemical compound CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 claims description 2
- 229960003896 Aminopterin Drugs 0.000 claims description 2
- 206010003571 Astrocytoma Diseases 0.000 claims description 2
- 229960002756 Azacitidine Drugs 0.000 claims description 2
- IUEWAGVJRJORLA-UHFFFAOYSA-N BMN673 Chemical compound CN1N=CN=C1C1C(NNC(=O)C2=CC(F)=C3)=C2C3=NC1C1=CC=C(F)C=C1 IUEWAGVJRJORLA-UHFFFAOYSA-N 0.000 claims description 2
- 206010004146 Basal cell carcinoma Diseases 0.000 claims description 2
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Belustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- 206010061691 Benign mesothelioma Diseases 0.000 claims description 2
- 206010004593 Bile duct cancer Diseases 0.000 claims description 2
- 210000003445 Biliary Tract Anatomy 0.000 claims description 2
- 206010005003 Bladder cancer Diseases 0.000 claims description 2
- 229960001561 Bleomycin Drugs 0.000 claims description 2
- 108010006654 Bleomycin Proteins 0.000 claims description 2
- 210000004556 Brain Anatomy 0.000 claims description 2
- 210000000481 Breast Anatomy 0.000 claims description 2
- 210000003123 Bronchioles Anatomy 0.000 claims description 2
- 102100019396 CDK2 Human genes 0.000 claims description 2
- 101710015564 CHEK1 Proteins 0.000 claims description 2
- FVLVBPDQNARYJU-KYZUINATSA-N CHEMBL1967746 Chemical compound C[C@H]1CC[C@H](NC(=O)N(CCCl)N=O)CC1 FVLVBPDQNARYJU-KYZUINATSA-N 0.000 claims description 2
- 229960004117 Capecitabine Drugs 0.000 claims description 2
- 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 claims description 2
- 208000009458 Carcinoma in Situ Diseases 0.000 claims description 2
- 206010008263 Cervical dysplasia Diseases 0.000 claims description 2
- 210000003679 Cervix Uteri Anatomy 0.000 claims description 2
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 2
- 229960004630 Chlorambucil Drugs 0.000 claims description 2
- JCKYGMPEJWAADB-UHFFFAOYSA-N Chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 claims description 2
- 208000006990 Cholangiocarcinoma Diseases 0.000 claims description 2
- 208000005243 Chondrosarcoma Diseases 0.000 claims description 2
- 208000006332 Choriocarcinoma Diseases 0.000 claims description 2
- WDDPHFBMKLOVOX-AYQXTPAHSA-N Clofarabine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1F WDDPHFBMKLOVOX-AYQXTPAHSA-N 0.000 claims description 2
- 206010048832 Colon adenoma Diseases 0.000 claims description 2
- 206010010356 Congenital anomaly Diseases 0.000 claims description 2
- 102000002554 Cyclin A Human genes 0.000 claims description 2
- 108010068192 Cyclin A Proteins 0.000 claims description 2
- 102000003909 Cyclin E Human genes 0.000 claims description 2
- 108090000257 Cyclin E Proteins 0.000 claims description 2
- 108010024986 Cyclin-Dependent Kinase 2 Proteins 0.000 claims description 2
- 229960004397 Cyclophosphamide Drugs 0.000 claims description 2
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 2
- 206010011732 Cyst Diseases 0.000 claims description 2
- 229960000975 Daunorubicin Drugs 0.000 claims description 2
- 229960004679 Doxorubicin Drugs 0.000 claims description 2
- 206010062805 Dysplastic naevus Diseases 0.000 claims description 2
- 229960001904 EPIRUBICIN Drugs 0.000 claims description 2
- AOJJSUZBOXZQNB-VTZDEGQISA-N EPIRUBICIN 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 2
- 206010014733 Endometrial cancer Diseases 0.000 claims description 2
- 206010014967 Ependymoma Diseases 0.000 claims description 2
- 210000002615 Epidermis Anatomy 0.000 claims description 2
- 210000003238 Esophagus Anatomy 0.000 claims description 2
- 229960001842 Estramustine Drugs 0.000 claims description 2
- 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 claims description 2
- 208000006168 Ewing Sarcoma Diseases 0.000 claims description 2
- 108060000495 FBXW7 Proteins 0.000 claims description 2
- 102100020077 FBXW7 Human genes 0.000 claims description 2
- 208000007659 Fibroadenoma Diseases 0.000 claims description 2
- ODKNJVUHOIMIIZ-RRKCRQDMSA-N Floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 claims description 2
- 229960000961 Floxuridine Drugs 0.000 claims description 2
- 206010016935 Follicular thyroid cancer Diseases 0.000 claims description 2
- 206010017758 Gastric cancer Diseases 0.000 claims description 2
- 208000007569 Giant Cell Tumors Diseases 0.000 claims description 2
- 208000005017 Glioblastoma Diseases 0.000 claims description 2
- 206010018404 Glucagonoma Diseases 0.000 claims description 2
- 206010018691 Granuloma Diseases 0.000 claims description 2
- 210000002216 Heart Anatomy 0.000 claims description 2
- 206010019629 Hepatic adenoma Diseases 0.000 claims description 2
- 208000006359 Hepatoblastoma Diseases 0.000 claims description 2
- 241000282619 Hylobates lar Species 0.000 claims description 2
- 229960000908 Idarubicin Drugs 0.000 claims description 2
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin hydrochloride 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 2
- 229960001101 Ifosfamide Drugs 0.000 claims description 2
- HOMGKSMUEGBAAB-UHFFFAOYSA-N Ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 claims description 2
- 229950002133 Iniparib Drugs 0.000 claims description 2
- 206010022498 Insulinoma Diseases 0.000 claims description 2
- 210000000936 Intestines Anatomy 0.000 claims description 2
- 208000009164 Islet Cell Adenoma Diseases 0.000 claims description 2
- 101710033922 KRAS Proteins 0.000 claims description 2
- 208000007766 Kaposi Sarcoma Diseases 0.000 claims description 2
- 210000001117 Keloid Anatomy 0.000 claims description 2
- 208000002260 Keloid Diseases 0.000 claims description 2
- 206010023330 Keloid scar Diseases 0.000 claims description 2
- 210000003734 Kidney Anatomy 0.000 claims description 2
- 210000000867 Larynx Anatomy 0.000 claims description 2
- 210000000088 Lip Anatomy 0.000 claims description 2
- 206010024627 Liposarcoma Diseases 0.000 claims description 2
- 210000004185 Liver Anatomy 0.000 claims description 2
- 208000002404 Liver Cell Adenoma Diseases 0.000 claims description 2
- 229950008991 Lobaplatin Drugs 0.000 claims description 2
- 210000004072 Lung Anatomy 0.000 claims description 2
- HAVFFEMDLROBGI-UHFFFAOYSA-N M8926C7ILX Chemical compound C1CC(O)CCN1CC1=CC=C(OC=2C3=C(C(NN=C33)=O)C=CC=2)C3=C1 HAVFFEMDLROBGI-UHFFFAOYSA-N 0.000 claims description 2
- 208000006644 Malignant Fibrous Histiocytoma Diseases 0.000 claims description 2
- UUVIQYKKKBJYJT-ZYUZMQFOSA-N Mannosulfan Chemical compound CS(=O)(=O)OC[C@@H](OS(C)(=O)=O)[C@@H](O)[C@H](O)[C@H](OS(C)(=O)=O)COS(C)(=O)=O UUVIQYKKKBJYJT-ZYUZMQFOSA-N 0.000 claims description 2
- 229960000733 Mannosulfan Drugs 0.000 claims description 2
- 208000000172 Medulloblastoma Diseases 0.000 claims description 2
- 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 2
- 210000002418 Meninges Anatomy 0.000 claims description 2
- 206010027406 Mesothelioma Diseases 0.000 claims description 2
- VFKZTMPDYBFSTM-KVTDHHQDSA-N Mitobronitol Chemical compound BrC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CBr VFKZTMPDYBFSTM-KVTDHHQDSA-N 0.000 claims description 2
- 229960004857 Mitomycin Drugs 0.000 claims description 2
- 208000010492 Mucinous Cystadenocarcinoma Diseases 0.000 claims description 2
- 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 2
- 208000009091 Myxoma Diseases 0.000 claims description 2
- 101710033916 NRAS Proteins 0.000 claims description 2
- 102100001119 NRAS Human genes 0.000 claims description 2
- 208000007538 Neurilemmoma Diseases 0.000 claims description 2
- 206010029260 Neuroblastoma Diseases 0.000 claims description 2
- VFEDRRNHLBGPNN-UHFFFAOYSA-N Nimustine Chemical compound CC1=NC=C(CNC(=O)N(CCCl)N=O)C(N)=N1 VFEDRRNHLBGPNN-UHFFFAOYSA-N 0.000 claims description 2
- OSTGTTZJOCZWJG-UHFFFAOYSA-N Nitrosourea Chemical compound NC(=O)N=NO OSTGTTZJOCZWJG-UHFFFAOYSA-N 0.000 claims description 2
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Nitrumon Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 claims description 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 2
- 208000000035 Osteochondroma Diseases 0.000 claims description 2
- 208000008798 Osteoma Diseases 0.000 claims description 2
- 210000001672 Ovary Anatomy 0.000 claims description 2
- 210000003101 Oviducts Anatomy 0.000 claims description 2
- 210000000496 Pancreas Anatomy 0.000 claims description 2
- 206010033701 Papillary thyroid cancer Diseases 0.000 claims description 2
- 208000007312 Paraganglioma Diseases 0.000 claims description 2
- 206010061332 Paraganglion neoplasm Diseases 0.000 claims description 2
- 229960002340 Pentostatin Drugs 0.000 claims description 2
- 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 claims description 2
- 206010034800 Phaeochromocytoma Diseases 0.000 claims description 2
- 210000003800 Pharynx Anatomy 0.000 claims description 2
- IIMIOEBMYPRQGU-UHFFFAOYSA-L Picoplatin Chemical compound N.[Cl-].[Cl-].[Pt+2].CC1=CC=CC=N1 IIMIOEBMYPRQGU-UHFFFAOYSA-L 0.000 claims description 2
- 229950005566 Picoplatin Drugs 0.000 claims description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 2
- 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 claims description 2
- 210000002307 Prostate Anatomy 0.000 claims description 2
- 102100008299 RBBP8 Human genes 0.000 claims description 2
- 101710036782 RBBP8 Proteins 0.000 claims description 2
- 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 claims description 2
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 claims description 2
- 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 claims description 2
- 229950009213 Rubitecan Drugs 0.000 claims description 2
- 102100009124 SMC1A Human genes 0.000 claims description 2
- 208000000097 Sertoli-Leydig Cell Tumor Diseases 0.000 claims description 2
- 210000003491 Skin Anatomy 0.000 claims description 2
- 210000003625 Skull Anatomy 0.000 claims description 2
- 210000002784 Stomach Anatomy 0.000 claims description 2
- 241000187747 Streptomyces Species 0.000 claims description 2
- 229960001052 Streptozocin Drugs 0.000 claims description 2
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N Streptozotocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 claims description 2
- 210000002536 Stromal Cells Anatomy 0.000 claims description 2
- WFWLQNSHRPWKFK-ZCFIWIBFSA-N Tegafur Chemical compound O=C1NC(=O)C(F)=CN1[C@@H]1OCCC1 WFWLQNSHRPWKFK-ZCFIWIBFSA-N 0.000 claims description 2
- 229960001278 Teniposide Drugs 0.000 claims description 2
- 208000001608 Teratocarcinoma Diseases 0.000 claims description 2
- 206010043276 Teratoma Diseases 0.000 claims description 2
- 210000001550 Testis Anatomy 0.000 claims description 2
- 229960005454 Thioguanine Drugs 0.000 claims description 2
- 210000001685 Thyroid Gland Anatomy 0.000 claims description 2
- 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 claims description 2
- 210000002105 Tongue Anatomy 0.000 claims description 2
- 206010044412 Transitional cell carcinoma Diseases 0.000 claims description 2
- AYNNSCRYTDRFCP-UHFFFAOYSA-N Triazene Chemical compound NN=N AYNNSCRYTDRFCP-UHFFFAOYSA-N 0.000 claims description 2
- 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 claims description 2
- UMKFEPPTGMDVMI-UHFFFAOYSA-N Trofosfamide Chemical compound ClCCN(CCCl)P1(=O)OCCCN1CCCl UMKFEPPTGMDVMI-UHFFFAOYSA-N 0.000 claims description 2
- NMUSYJAQQFHJEW-KVTDHHQDSA-N U-18,496 Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 claims description 2
- IDPUKCWIGUEADI-UHFFFAOYSA-N Uramustine Chemical compound ClCCN(CCCl)C1=CNC(=O)NC1=O IDPUKCWIGUEADI-UHFFFAOYSA-N 0.000 claims description 2
- 229950008158 Uramustine Drugs 0.000 claims description 2
- 210000003708 Urethra Anatomy 0.000 claims description 2
- 210000003932 Urinary Bladder Anatomy 0.000 claims description 2
- 210000004291 Uterus Anatomy 0.000 claims description 2
- 210000001215 Vagina Anatomy 0.000 claims description 2
- 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 2
- 208000009540 Villous Adenoma Diseases 0.000 claims description 2
- 240000006365 Vitis vinifera Species 0.000 claims description 2
- 235000014787 Vitis vinifera Nutrition 0.000 claims description 2
- 210000003905 Vulva Anatomy 0.000 claims description 2
- 206010048214 Xanthoma Diseases 0.000 claims description 2
- AOCCBINRVIKJHY-UHFFFAOYSA-N Yamafur Chemical compound CCCCCCNC(=O)N1C=C(F)C(=O)NC1=O AOCCBINRVIKJHY-UHFFFAOYSA-N 0.000 claims description 2
- 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 claims description 2
- 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 claims description 2
- USZYSDMBJDPRIF-SVEJIMAYSA-N aclacinomycin A Chemical compound O([C@H]1[C@@H](O)C[C@@H](O[C@H]1C)O[C@H]1[C@H](C[C@@H](O[C@H]1C)O[C@H]1C[C@]([C@@H](C2=CC=3C(=O)C4=CC=CC(O)=C4C(=O)C=3C(O)=C21)C(=O)OC)(O)CC)N(C)C)[C@H]1CCC(=O)[C@H](C)O1 USZYSDMBJDPRIF-SVEJIMAYSA-N 0.000 claims description 2
- 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 claims description 2
- 229960000473 altretamine Drugs 0.000 claims description 2
- 229960002550 amrubicin Drugs 0.000 claims description 2
- 239000003242 anti bacterial agent Substances 0.000 claims description 2
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 125000003725 azepanyl group Chemical group 0.000 claims description 2
- NOWKCMXCCJGMRR-UHFFFAOYSA-N aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims description 2
- 229960002707 bendamustine Drugs 0.000 claims description 2
- 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 2
- 201000005216 brain cancer Diseases 0.000 claims description 2
- 201000003149 breast fibroadenoma Diseases 0.000 claims description 2
- 201000002143 bronchus adenoma Diseases 0.000 claims description 2
- 229960002092 busulfan Drugs 0.000 claims description 2
- 125000004432 carbon atoms Chemical group C* 0.000 claims description 2
- 229960003261 carmofur Drugs 0.000 claims description 2
- 229960005243 carmustine Drugs 0.000 claims description 2
- 230000012820 cell cycle checkpoint Effects 0.000 claims description 2
- 230000030833 cell death Effects 0.000 claims description 2
- 201000010881 cervical cancer Diseases 0.000 claims description 2
- 201000005217 chondroblastoma Diseases 0.000 claims description 2
- 201000005262 chondroma Diseases 0.000 claims description 2
- 201000009047 chordoma Diseases 0.000 claims description 2
- 229960000928 clofarabine Drugs 0.000 claims description 2
- 201000011231 colorectal cancer Diseases 0.000 claims description 2
- 229960003901 dacarbazine Drugs 0.000 claims description 2
- 125000005047 dihydroimidazolyl group Chemical group N1(CNC=C1)* 0.000 claims description 2
- 125000004655 dihydropyridinyl group Chemical group N1(CC=CC=C1)* 0.000 claims description 2
- 125000005053 dihydropyrimidinyl group Chemical group N1(CN=CC=C1)* 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000002500 effect on skin Effects 0.000 claims description 2
- 201000004101 esophageal cancer Diseases 0.000 claims description 2
- 201000006850 familial medullary thyroid carcinoma Diseases 0.000 claims description 2
- 230000001605 fetal Effects 0.000 claims description 2
- 239000000835 fiber Substances 0.000 claims description 2
- 229960004783 fotemustine Drugs 0.000 claims description 2
- YAKWPXVTIGTRJH-UHFFFAOYSA-N fotemustine Chemical compound CCOP(=O)(OCC)C(C)NC(=O)N(CCCl)N=O YAKWPXVTIGTRJH-UHFFFAOYSA-N 0.000 claims description 2
- 125000000524 functional group Chemical group 0.000 claims description 2
- 230000002496 gastric Effects 0.000 claims description 2
- 201000000052 gastrinoma Diseases 0.000 claims description 2
- 201000010915 glioblastoma multiforme Diseases 0.000 claims description 2
- 235000009754 grape Nutrition 0.000 claims description 2
- 235000012333 grape Nutrition 0.000 claims description 2
- 238000005658 halogenation reaction Methods 0.000 claims description 2
- 201000002735 hepatocellular adenoma Diseases 0.000 claims description 2
- 238000002744 homologous recombination Methods 0.000 claims description 2
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 2
- 125000003965 isoxazolidinyl group Chemical group 0.000 claims description 2
- 210000002429 large intestine Anatomy 0.000 claims description 2
- 201000007270 liver cancer Diseases 0.000 claims description 2
- 229960002247 lomustine Drugs 0.000 claims description 2
- 208000009018 medullary Thyroid cancer Diseases 0.000 claims description 2
- 229960001924 melphalan Drugs 0.000 claims description 2
- 229910052751 metal Inorganic materials 0.000 claims description 2
- 239000002184 metal Substances 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 229960005485 mitobronitol Drugs 0.000 claims description 2
- 230000000051 modifying Effects 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- 201000009251 multiple myeloma Diseases 0.000 claims description 2
- 210000000653 nervous system Anatomy 0.000 claims description 2
- 229960001420 nimustine Drugs 0.000 claims description 2
- 201000010133 oligodendroglioma Diseases 0.000 claims description 2
- 201000008482 osteoarthritis Diseases 0.000 claims description 2
- 125000000160 oxazolidinyl group Chemical group 0.000 claims description 2
- 201000008129 pancreatic ductal adenocarcinoma Diseases 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 238000006366 phosphorylation reaction Methods 0.000 claims description 2
- 230000000865 phosphorylative Effects 0.000 claims description 2
- 229960001221 pirarubicin Drugs 0.000 claims description 2
- 229960004694 prednimustine Drugs 0.000 claims description 2
- 201000001692 primary autosomal recessive microcephaly 1 Diseases 0.000 claims description 2
- 230000001737 promoting Effects 0.000 claims description 2
- 201000004681 psoriasis Diseases 0.000 claims description 2
- 125000003072 pyrazolidinyl group Chemical group 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 230000000637 radiosensitizating Effects 0.000 claims description 2
- 229960004432 raltitrexed Drugs 0.000 claims description 2
- 229960002185 ranimustine Drugs 0.000 claims description 2
- 201000000582 retinoblastoma Diseases 0.000 claims description 2
- 229960003440 semustine Drugs 0.000 claims description 2
- 230000019491 signal transduction Effects 0.000 claims description 2
- 210000000813 small intestine Anatomy 0.000 claims description 2
- 201000011549 stomach cancer Diseases 0.000 claims description 2
- 108010004731 structural maintenance of chromosome protein 1 Proteins 0.000 claims description 2
- 229960001674 tegafur Drugs 0.000 claims description 2
- 125000001984 thiazolidinyl group Chemical group 0.000 claims description 2
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 2
- RMFNGLHOFHJMHN-UHFFFAOYSA-L triplatin tetranitrate Chemical compound [O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[NH3+][Pt-2]([NH3+])(Cl)[NH2+]CCCCCC[NH2+][Pt-2]([NH3+])([NH3+])[NH2+]CCCCCC[NH2+][Pt-2]([NH3+])([NH3+])Cl RMFNGLHOFHJMHN-UHFFFAOYSA-L 0.000 claims description 2
- 229950002860 triplatin tetranitrate Drugs 0.000 claims description 2
- 229960000875 trofosfamide Drugs 0.000 claims description 2
- 229960001055 uracil mustard Drugs 0.000 claims description 2
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 2
- 229960000653 valrubicin Drugs 0.000 claims description 2
- JNAHVYVRKWKWKQ-CYBMUJFWSA-N veliparib Chemical compound N=1C2=CC=CC(C(N)=O)=C2NC=1[C@@]1(C)CCCN1 JNAHVYVRKWKWKQ-CYBMUJFWSA-N 0.000 claims description 2
- 229960000641 zorubicin Drugs 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 238000005755 formation reaction Methods 0.000 claims 1
- 230000001939 inductive effect Effects 0.000 claims 1
- 238000004806 packaging method and process Methods 0.000 claims 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 0 *c1cc2nc(N)c(C(NN)=O)[n]2nc1* Chemical compound *c1cc2nc(N)c(C(NN)=O)[n]2nc1* 0.000 description 52
- NHRCDBNBRQOQCJ-UHFFFAOYSA-N CCOc(ccnc1)c1NC(c1c(cccc2)[n]2nc1N)=O Chemical compound CCOc(ccnc1)c1NC(c1c(cccc2)[n]2nc1N)=O NHRCDBNBRQOQCJ-UHFFFAOYSA-N 0.000 description 2
- DSEDUUFHHGXVHG-UHFFFAOYSA-N CN(CC1)CCC1Oc(ccnc1)c1NC(c1c(N)nc2[n]1nc(C(F)(F)F)cc2)=O Chemical compound CN(CC1)CCC1Oc(ccnc1)c1NC(c1c(N)nc2[n]1nc(C(F)(F)F)cc2)=O DSEDUUFHHGXVHG-UHFFFAOYSA-N 0.000 description 2
- MIMBKZPNNFLXDB-UHFFFAOYSA-N CN(CC1)CCC1Oc(ccnc1)c1NC(c1c(N)nc2[n]1nccc2)=O Chemical compound CN(CC1)CCC1Oc(ccnc1)c1NC(c1c(N)nc2[n]1nccc2)=O MIMBKZPNNFLXDB-UHFFFAOYSA-N 0.000 description 2
- SGFTYMGAFPRPNP-UHFFFAOYSA-N CN(CC1)CCN1C(C(CC1)CCN1c(c(F)cnc1)c1NC(c1c(cccc2)[n]2nc1N)=O)=O Chemical compound CN(CC1)CCN1C(C(CC1)CCN1c(c(F)cnc1)c1NC(c1c(cccc2)[n]2nc1N)=O)=O SGFTYMGAFPRPNP-UHFFFAOYSA-N 0.000 description 2
- VOTOWVOBHDEJEB-UHFFFAOYSA-N Nc1n[n](cccc2)c2c1C(Nc(cncc1)c1N1CCCCC1)=O Chemical compound Nc1n[n](cccc2)c2c1C(Nc(cncc1)c1N1CCCCC1)=O VOTOWVOBHDEJEB-UHFFFAOYSA-N 0.000 description 2
- CFCUWKMKBJTWLW-BGLFSJPPSA-N (2S,3S)-2-[(2S,4R,5R,6R)-4-[(2S,4R,5R,6R)-4-[(2S,4S,5R,6R)-4,5-dihydroxy-4,6-dimethyloxan-2-yl]oxy-5-hydroxy-6-methyloxan-2-yl]oxy-5-hydroxy-6-methyloxan-2-yl]oxy-3-[(1S,3S,4R)-3,4-dihydroxy-1-methoxy-2-oxopentyl]-6-[(2S,4R,5S,6R)-4-[(2S,4R,5S,6R)-4,5-dih 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-BGLFSJPPSA-N 0.000 description 1
- 206010022114 Injury Diseases 0.000 description 1
- 229960003171 Plicamycin Drugs 0.000 description 1
- 239000003560 cancer drug Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000003389 potentiating Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US2013/073482 WO2015084384A1 (en) | 2013-12-06 | 2013-12-06 | Compounds useful as inhibitors of atr kinase |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2016540773A JP2016540773A (ja) | 2016-12-28 |
| JP2016540773A5 true JP2016540773A5 (lt) | 2017-02-09 |
Family
ID=49877037
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016536710A Pending JP2016540773A (ja) | 2013-12-06 | 2013-12-06 | Ａｔｒキナーゼの阻害剤として有用な化合物 |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP3077393A1 (lt) |
| JP (1) | JP2016540773A (lt) |
| WO (1) | WO2015084384A1 (lt) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB201516504D0 (en) * | 2015-09-17 | 2015-11-04 | Astrazeneca Ab | Imadazo(4,5-c)quinolin-2-one Compounds and their use in treating cancer |
| JP7187308B2 (ja) | 2015-09-30 | 2022-12-12 | バーテックス ファーマシューティカルズ インコーポレイテッド | Ｄｎａ損傷剤とａｔｒ阻害剤との組み合わせを使用する、がんを処置するための方法 |
| EP3461480A1 (en) | 2017-09-27 | 2019-04-03 | Onxeo | Combination of a dna damage response cell cycle checkpoint inhibitors and belinostat for treating cancer |
| WO2020064971A1 (en) | 2018-09-26 | 2020-04-02 | Merck Patent Gmbh | Combination of a pd-1 antagonist, an atr inhibitor and a platinating agent for the treatment of cancer |
| EP3866785A1 (en) | 2018-10-15 | 2021-08-25 | Merck Patent GmbH | Combination therapy utilizing dna alkylating agents and atr inhibitors |
| EP4230628A1 (en) | 2020-10-16 | 2023-08-23 | Shanghai de Novo Pharmatech Co., Ltd. | Triheterocyclic derivative, and pharmaceutical composition and application thereof |
| CN115466258A (zh) * | 2021-06-11 | 2022-12-13 | 成都苑东生物制药股份有限公司 | Atr抑制剂及其用途 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2049541B1 (en) * | 2006-08-04 | 2015-09-23 | Takeda Pharmaceutical Company Limited | N-[5-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)-2-methylphenyl]-1,3-dimethyl-1h-pyrazole-5-carboxamide as vegfr inhibitor |
| UA110324C2 (en) * | 2009-07-02 | 2015-12-25 | Genentech Inc | Jak inhibitory compounds based on pyrazolo pyrimidine |
| US9018395B2 (en) * | 2011-01-27 | 2015-04-28 | Université de Montréal | Pyrazolopyridine and pyrazolopyrimidine derivatives as melanocortin-4 receptor modulators |
-
2013
- 2013-12-06 JP JP2016536710A patent/JP2016540773A/ja active Pending
- 2013-12-06 EP EP13811718.9A patent/EP3077393A1/en not_active Withdrawn
- 2013-12-06 WO PCT/US2013/073482 patent/WO2015084384A1/en active Application Filing
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2015515478A5 (lt) | ||
| JP2016512816A5 (lt) | ||
| HRP20191375T1 (hr) | Postupak liječenja raka upotrebom kombinacije chk1 i atr inhibitora | |
| HRP20211034T1 (hr) | 2-amino-n-(piperidin-1-il-piridin-3-il)pirazolo[1,5alfa]pirimidin-3-karboksamid kao inhibitor atr kinaze | |
| JP2016512239A5 (lt) | ||
| JP2014510151A5 (lt) | ||
| JP2016512815A5 (lt) | ||
| JP2016540773A5 (lt) | ||
| JP2016501244A5 (lt) | ||
| JP2017186385A5 (lt) | ||
| CN108771681B (zh) | 作为dna-pk抑制剂的化合物及其氘化衍生物的共晶 | |
| JP2013529643A5 (lt) | ||
| SI2833973T1 (en) | Compounds useful as inhibitors of ATR kinase and their combination therapy | |
| ES2663222T3 (es) | Derivados de pirazina útiles como inhibidores de la quinasa ATR | |
| JP2013529200A5 (lt) | ||
| JP2013526538A5 (lt) | ||
| CN105899493B (zh) | 用于抑制shp2活性的1-(三嗪-3-基/哒嗪-3-基)-哌(-嗪)啶衍生物及其组合物 | |
| JP2013529199A5 (lt) | ||
| JP2013526540A5 (lt) | ||
| JP2013526539A5 (lt) | ||
| RU2605335C2 (ru) | Комбинированная терапия противоопухолевым алкалоидом | |
| JP2018529713A5 (lt) | ||
| JP2012508260A5 (lt) | ||
| CN113454080A (zh) | 化合物、药物组合物和制备化合物的方法以及其使用方法 | |
| RU2007134571A (ru) | Комбинация и способы введения терапевтических средств и комбинированной терапии |