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
- 238000000034 method Methods 0.000 claims description 90
- 239000000203 mixture Substances 0.000 claims description 87
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 73
- 206010028980 Neoplasm Diseases 0.000 claims description 65
- 150000003839 salts Chemical class 0.000 claims description 56
- 210000004027 cell Anatomy 0.000 claims description 52
- 229940002612 prodrug Drugs 0.000 claims description 51
- 239000000651 prodrug Substances 0.000 claims description 51
- 201000011510 cancer Diseases 0.000 claims description 47
- 125000001931 aliphatic group Chemical group 0.000 claims description 46
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 38
- 125000005842 heteroatom Chemical group 0.000 claims description 38
- 229910052757 nitrogen Inorganic materials 0.000 claims description 38
- 229910052717 sulfur Chemical group 0.000 claims description 38
- 239000011593 sulfur Chemical group 0.000 claims description 38
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 37
- 229910052760 oxygen Inorganic materials 0.000 claims description 37
- 239000001301 oxygen Substances 0.000 claims description 37
- 229960005277 gemcitabine Drugs 0.000 claims description 33
- 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
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 28
- 229920006395 saturated elastomer Polymers 0.000 claims description 28
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 26
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 26
- 201000002528 pancreatic cancer Diseases 0.000 claims description 26
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 26
- 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 atom Chemical group 0.000 claims description 21
- 239000003814 drug Substances 0.000 claims description 21
- 229940124597 therapeutic agent Drugs 0.000 claims description 21
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 19
- 229960004316 cisplatin Drugs 0.000 claims description 19
- 208000009956 adenocarcinoma Diseases 0.000 claims description 18
- 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
- 230000005855 radiation Effects 0.000 claims description 16
- 206010025323 Lymphomas Diseases 0.000 claims description 14
- 206010039491 Sarcoma Diseases 0.000 claims description 14
- 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
- 230000005865 ionizing radiation Effects 0.000 claims description 14
- 229910052697 platinum Inorganic materials 0.000 claims description 14
- 102100033688 DNA ligase 3 Human genes 0.000 claims description 12
- 101001113440 Homo sapiens Poly [ADP-ribose] polymerase 2 Proteins 0.000 claims description 12
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 12
- 108010064218 Poly (ADP-Ribose) Polymerase-1 Proteins 0.000 claims description 12
- 102100023712 Poly [ADP-ribose] polymerase 1 Human genes 0.000 claims description 12
- 102100023652 Poly [ADP-ribose] polymerase 2 Human genes 0.000 claims description 12
- 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 12
- 229960004562 carboplatin Drugs 0.000 claims description 12
- 201000005202 lung cancer Diseases 0.000 claims description 12
- 208000020816 lung neoplasm Diseases 0.000 claims description 12
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 12
- 238000001959 radiotherapy Methods 0.000 claims description 12
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 12
- 238000011282 treatment Methods 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 229940100198 alkylating agent Drugs 0.000 claims description 10
- 239000002168 alkylating agent Substances 0.000 claims description 10
- 230000000340 anti-metabolite Effects 0.000 claims description 10
- 229940100197 antimetabolite Drugs 0.000 claims description 10
- 239000002256 antimetabolite Substances 0.000 claims description 10
- 206010041823 squamous cell carcinoma Diseases 0.000 claims description 10
- 201000009030 Carcinoma Diseases 0.000 claims description 8
- 108010060248 DNA Ligase ATP Proteins 0.000 claims description 8
- 102100029995 DNA ligase 1 Human genes 0.000 claims description 8
- 101000927847 Homo sapiens DNA ligase 3 Proteins 0.000 claims description 8
- 206010024612 Lipoma 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
- 206010016629 fibroma Diseases 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
- 101150005648 polB gene Proteins 0.000 claims description 8
- 238000009472 formulation Methods 0.000 claims description 7
- MDOJTZQKHMAPBK-UHFFFAOYSA-N 4-iodo-3-nitrobenzamide Chemical compound NC(=O)C1=CC=C(I)C([N+]([O-])=O)=C1 MDOJTZQKHMAPBK-UHFFFAOYSA-N 0.000 claims description 6
- 102000002804 Ataxia Telangiectasia Mutated Proteins Human genes 0.000 claims description 6
- 108010004586 Ataxia Telangiectasia Mutated Proteins Proteins 0.000 claims description 6
- 201000008808 Fibrosarcoma Diseases 0.000 claims description 6
- 206010041067 Small cell lung cancer Diseases 0.000 claims description 6
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide 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 effect 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
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 230000003211 malignant effect Effects 0.000 claims description 6
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 claims description 6
- 210000000214 mouth Anatomy 0.000 claims description 6
- FDLYAMZZIXQODN-UHFFFAOYSA-N olaparib Chemical compound FC1=CC=C(CC=2C3=CC=CC=C3C(=O)NN=2)C=C1C(=O)N(CC1)CCN1C(=O)C1CC1 FDLYAMZZIXQODN-UHFFFAOYSA-N 0.000 claims description 6
- 201000009410 rhabdomyosarcoma Diseases 0.000 claims description 6
- 230000001235 sensitizing effect Effects 0.000 claims description 6
- 208000000587 small cell lung carcinoma Diseases 0.000 claims description 6
- 229960004964 temozolomide Drugs 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 125000003566 oxetanyl group Chemical group 0.000 claims description 5
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 claims description 4
- 102100035886 Adenine DNA glycosylase Human genes 0.000 claims description 4
- 201000003076 Angiosarcoma Diseases 0.000 claims description 4
- 206010006187 Breast cancer Diseases 0.000 claims description 4
- 208000026310 Breast neoplasm Diseases 0.000 claims description 4
- 101100452003 Caenorhabditis elegans ape-1 gene Proteins 0.000 claims description 4
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 claims description 4
- 102100025064 Cellular tumor antigen p53 Human genes 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
- 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 claims description 4
- 108020001738 DNA Glycosylase Proteins 0.000 claims description 4
- 230000005778 DNA damage Effects 0.000 claims description 4
- 231100000277 DNA damage Toxicity 0.000 claims description 4
- 102000028381 DNA glycosylase Human genes 0.000 claims description 4
- 102100039116 DNA repair protein RAD50 Human genes 0.000 claims description 4
- 108010063362 DNA-(Apurinic or Apyrimidinic Site) Lyase Proteins 0.000 claims description 4
- 102000010719 DNA-(Apurinic or Apyrimidinic Site) Lyase Human genes 0.000 claims description 4
- 102100035619 DNA-(apurinic or apyrimidinic site) lyase Human genes 0.000 claims description 4
- 102100039128 DNA-3-methyladenine glycosylase Human genes 0.000 claims description 4
- 102100033996 Double-strand break repair protein MRE11 Human genes 0.000 claims description 4
- 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 4
- 101100010303 Drosophila melanogaster PolG1 gene Proteins 0.000 claims description 4
- 208000001976 Endocrine Gland Neoplasms Diseases 0.000 claims description 4
- 102100028778 Endonuclease 8-like 1 Human genes 0.000 claims description 4
- 102100028779 Endonuclease 8-like 2 Human genes 0.000 claims description 4
- 102100028773 Endonuclease 8-like 3 Human genes 0.000 claims description 4
- 102100021710 Endonuclease III-like protein 1 Human genes 0.000 claims description 4
- 108010042407 Endonucleases Proteins 0.000 claims description 4
- 102000004533 Endonucleases Human genes 0.000 claims description 4
- 102100026121 Flap endonuclease 1 Human genes 0.000 claims description 4
- 108090000652 Flap endonucleases Proteins 0.000 claims description 4
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 4
- 102100026406 G/T mismatch-specific thymine DNA glycosylase Human genes 0.000 claims description 4
- 208000032612 Glial tumor Diseases 0.000 claims description 4
- 206010018338 Glioma Diseases 0.000 claims description 4
- 208000002927 Hamartoma Diseases 0.000 claims description 4
- 208000001258 Hemangiosarcoma Diseases 0.000 claims description 4
- 102100034533 Histone H2AX Human genes 0.000 claims description 4
- 101001000351 Homo sapiens Adenine DNA glycosylase Proteins 0.000 claims description 4
- 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 claims description 4
- 101000863770 Homo sapiens DNA ligase 1 Proteins 0.000 claims description 4
- 101000743929 Homo sapiens DNA repair protein RAD50 Proteins 0.000 claims description 4
- 101001137256 Homo sapiens DNA-(apurinic or apyrimidinic site) lyase Proteins 0.000 claims description 4
- 101000744174 Homo sapiens DNA-3-methyladenine glycosylase Proteins 0.000 claims description 4
- 101000591400 Homo sapiens Double-strand break repair protein MRE11 Proteins 0.000 claims description 4
- 101001123824 Homo sapiens Endonuclease 8-like 1 Proteins 0.000 claims description 4
- 101001123823 Homo sapiens Endonuclease 8-like 2 Proteins 0.000 claims description 4
- 101001123819 Homo sapiens Endonuclease 8-like 3 Proteins 0.000 claims description 4
- 101000970385 Homo sapiens Endonuclease III-like protein 1 Proteins 0.000 claims description 4
- 101000835738 Homo sapiens G/T mismatch-specific thymine DNA glycosylase Proteins 0.000 claims description 4
- 101001067891 Homo sapiens Histone H2AX Proteins 0.000 claims description 4
- 101000619640 Homo sapiens Leucine-rich repeats and immunoglobulin-like domains protein 1 Proteins 0.000 claims description 4
- 101000581326 Homo sapiens Mediator of DNA damage checkpoint protein 1 Proteins 0.000 claims description 4
- 101000615492 Homo sapiens Methyl-CpG-binding domain protein 4 Proteins 0.000 claims description 4
- 101000581289 Homo sapiens Microcephalin Proteins 0.000 claims description 4
- 101001128138 Homo sapiens NACHT, LRR and PYD domains-containing protein 2 Proteins 0.000 claims description 4
- 101000981336 Homo sapiens Nibrin Proteins 0.000 claims description 4
- 101000777277 Homo sapiens Serine/threonine-protein kinase Chk2 Proteins 0.000 claims description 4
- 101000664956 Homo sapiens Single-strand selective monofunctional uracil DNA glycosylase Proteins 0.000 claims description 4
- 206010021143 Hypoxia Diseases 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
- 208000018142 Leiomyosarcoma Diseases 0.000 claims description 4
- 102100027643 Mediator of DNA damage checkpoint protein 1 Human genes 0.000 claims description 4
- 102100021290 Methyl-CpG-binding domain protein 4 Human genes 0.000 claims description 4
- 102100027632 Microcephalin Human genes 0.000 claims description 4
- 201000004404 Neurofibroma Diseases 0.000 claims description 4
- 102100024403 Nibrin Human genes 0.000 claims description 4
- 206010033128 Ovarian cancer Diseases 0.000 claims description 4
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 4
- 101150078890 POLG gene Proteins 0.000 claims description 4
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 claims description 4
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 claims description 4
- 101000595993 Phyllomedusa sauvagei Phylloseptin-S1 Proteins 0.000 claims description 4
- 108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 claims description 4
- 102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 claims description 4
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 claims description 4
- 108010021757 Polynucleotide 5'-Hydroxyl-Kinase Proteins 0.000 claims description 4
- 102000008422 Polynucleotide 5'-hydroxyl-kinase Human genes 0.000 claims description 4
- 102100031075 Serine/threonine-protein kinase Chk2 Human genes 0.000 claims description 4
- 102100038661 Single-strand selective monofunctional uracil DNA glycosylase Human genes 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
- 102100037111 Uracil-DNA glycosylase Human genes 0.000 claims description 4
- 101710160987 Uracil-DNA glycosylase Proteins 0.000 claims description 4
- 208000008383 Wilms tumor Diseases 0.000 claims description 4
- 102000002258 X-ray Repair Cross Complementing Protein 1 Human genes 0.000 claims description 4
- 108010000443 X-ray Repair Cross Complementing Protein 1 Proteins 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
- 229940127093 camptothecin Drugs 0.000 claims description 4
- 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 4
- 210000000845 cartilage Anatomy 0.000 claims description 4
- 208000006990 cholangiocarcinoma Diseases 0.000 claims description 4
- 229960002436 cladribine Drugs 0.000 claims description 4
- 210000001072 colon Anatomy 0.000 claims description 4
- 229960000684 cytarabine Drugs 0.000 claims description 4
- 230000007547 defect Effects 0.000 claims description 4
- 230000007812 deficiency Effects 0.000 claims description 4
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 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
- 229960002949 fluorouracil Drugs 0.000 claims description 4
- 208000005017 glioblastoma Diseases 0.000 claims description 4
- 201000010536 head and neck cancer Diseases 0.000 claims description 4
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 4
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 4
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 4
- 230000001146 hypoxic effect Effects 0.000 claims description 4
- 229960004768 irinotecan Drugs 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
- 201000010260 leiomyoma Diseases 0.000 claims description 4
- 230000036244 malformation Effects 0.000 claims description 4
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical group ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 claims description 4
- 229960004961 mechlorethamine Drugs 0.000 claims description 4
- 201000001441 melanoma Diseases 0.000 claims description 4
- 206010027191 meningioma Diseases 0.000 claims description 4
- 229960001428 mercaptopurine Drugs 0.000 claims description 4
- 229960000485 methotrexate Drugs 0.000 claims description 4
- 229950007221 nedaplatin Drugs 0.000 claims description 4
- 201000008026 nephroblastoma Diseases 0.000 claims description 4
- 229960000572 olaparib Drugs 0.000 claims description 4
- 201000008968 osteosarcoma Diseases 0.000 claims description 4
- 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 4
- 229960001756 oxaliplatin Drugs 0.000 claims description 4
- 229960005079 pemetrexed Drugs 0.000 claims description 4
- QOFFJEBXNKRSPX-ZDUSSCGKSA-N pemetrexed Chemical compound C1=N[C]2NC(N)=NC(=O)C2=C1CCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 QOFFJEBXNKRSPX-ZDUSSCGKSA-N 0.000 claims description 4
- 125000004193 piperazinyl group Chemical group 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 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
- 229960000624 procarbazine Drugs 0.000 claims description 4
- 210000000664 rectum Anatomy 0.000 claims description 4
- 238000007363 ring formation reaction Methods 0.000 claims description 4
- 190014017285 satraplatin Chemical compound 0.000 claims description 4
- 229960005399 satraplatin Drugs 0.000 claims description 4
- 229960000303 topotecan Drugs 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
- -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
- FPVKHBSQESCIEP-UHFFFAOYSA-N (8S)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol Natural products C1C(O)C(CO)OC1N1C(NC=NCC2O)=C2N=C1 FPVKHBSQESCIEP-UHFFFAOYSA-N 0.000 claims description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-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
- 125000001845 4 membered carbocyclic group Chemical group 0.000 claims description 2
- 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 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
- IDPUKCWIGUEADI-UHFFFAOYSA-N 5-[bis(2-chloroethyl)amino]uracil Chemical compound ClCCN(CCCl)C1=CNC(=O)NC1=O IDPUKCWIGUEADI-UHFFFAOYSA-N 0.000 claims description 2
- NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 claims description 2
- WYWHKKSPHMUBEB-UHFFFAOYSA-N 6-Mercaptoguanine Natural products N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 claims description 2
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 claims description 2
- 206010001233 Adenoma benign Diseases 0.000 claims description 2
- 206010003571 Astrocytoma Diseases 0.000 claims description 2
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims description 2
- 206010004146 Basal cell carcinoma Diseases 0.000 claims description 2
- 206010004593 Bile duct cancer Diseases 0.000 claims description 2
- 206010005003 Bladder cancer Diseases 0.000 claims description 2
- 108010006654 Bleomycin Proteins 0.000 claims description 2
- 206010005969 Bone giant cell tumour Diseases 0.000 claims description 2
- 208000018084 Bone neoplasm Diseases 0.000 claims description 2
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 2
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 claims description 2
- FVLVBPDQNARYJU-XAHDHGMMSA-N C[C@H]1CCC(CC1)NC(=O)N(CCCl)N=O Chemical compound C[C@H]1CCC(CC1)NC(=O)N(CCCl)N=O FVLVBPDQNARYJU-XAHDHGMMSA-N 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
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 claims description 2
- 208000009458 Carcinoma in Situ Diseases 0.000 claims description 2
- AOCCBINRVIKJHY-UHFFFAOYSA-N Carmofur Chemical compound CCCCCCNC(=O)N1C=C(F)C(=O)NC1=O AOCCBINRVIKJHY-UHFFFAOYSA-N 0.000 claims description 2
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 claims description 2
- 206010008263 Cervical dysplasia Diseases 0.000 claims description 2
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 2
- 201000005262 Chondroma Diseases 0.000 claims description 2
- 208000005243 Chondrosarcoma Diseases 0.000 claims description 2
- 201000009047 Chordoma Diseases 0.000 claims description 2
- 208000006332 Choriocarcinoma Diseases 0.000 claims description 2
- 206010048832 Colon adenoma Diseases 0.000 claims description 2
- 206010009944 Colon cancer Diseases 0.000 claims description 2
- 208000001333 Colorectal Neoplasms 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
- 102100036239 Cyclin-dependent kinase 2 Human genes 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
- 102100039524 DNA endonuclease RBBP8 Human genes 0.000 claims description 2
- 108010092160 Dactinomycin Proteins 0.000 claims description 2
- 208000000471 Dysplastic Nevus Syndrome Diseases 0.000 claims description 2
- 206010062805 Dysplastic naevus Diseases 0.000 claims description 2
- 206010014733 Endometrial cancer Diseases 0.000 claims description 2
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 2
- 206010014967 Ependymoma Diseases 0.000 claims description 2
- 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 2
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 2
- 208000006168 Ewing Sarcoma Diseases 0.000 claims description 2
- 208000005917 Exostoses Diseases 0.000 claims description 2
- 102100028138 F-box/WD repeat-containing protein 7 Human genes 0.000 claims description 2
- 201000006850 Familial medullary thyroid carcinoma Diseases 0.000 claims description 2
- 208000007659 Fibroadenoma Diseases 0.000 claims description 2
- 206010016935 Follicular thyroid cancer Diseases 0.000 claims description 2
- 101710113436 GTPase KRas Proteins 0.000 claims description 2
- 102100039788 GTPase NRas Human genes 0.000 claims description 2
- 201000010915 Glioblastoma multiforme Diseases 0.000 claims description 2
- 201000005409 Gliomatosis cerebri Diseases 0.000 claims description 2
- 206010018404 Glucagonoma Diseases 0.000 claims description 2
- 206010018691 Granuloma Diseases 0.000 claims description 2
- 206010019629 Hepatic adenoma Diseases 0.000 claims description 2
- 101001060231 Homo sapiens F-box/WD repeat-containing protein 7 Proteins 0.000 claims description 2
- 101000744505 Homo sapiens GTPase NRas Proteins 0.000 claims description 2
- 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 2
- 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 2
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 claims description 2
- 208000009164 Islet Cell Adenoma Diseases 0.000 claims description 2
- 208000007766 Kaposi sarcoma Diseases 0.000 claims description 2
- 208000002260 Keloid Diseases 0.000 claims description 2
- 206010023330 Keloid scar Diseases 0.000 claims description 2
- 208000002404 Liver Cell Adenoma Diseases 0.000 claims description 2
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 claims description 2
- 208000006644 Malignant Fibrous Histiocytoma Diseases 0.000 claims description 2
- 208000009018 Medullary thyroid cancer Diseases 0.000 claims description 2
- 208000000172 Medulloblastoma Diseases 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
- 229930192392 Mitomycin Natural products 0.000 claims description 2
- 206010073148 Multiple endocrine neoplasia type 2A Diseases 0.000 claims description 2
- 208000034578 Multiple myelomas 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
- 206010029260 Neuroblastoma Diseases 0.000 claims description 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 2
- 201000010133 Oligodendroglioma Diseases 0.000 claims description 2
- 108700020796 Oncogene Proteins 0.000 claims description 2
- 208000000035 Osteochondroma Diseases 0.000 claims description 2
- 206010033701 Papillary thyroid cancer Diseases 0.000 claims description 2
- 206010061332 Paraganglion neoplasm Diseases 0.000 claims description 2
- 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 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
- 201000004681 Psoriasis Diseases 0.000 claims description 2
- 101150097169 RBBP8 gene 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
- 201000000582 Retinoblastoma Diseases 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
- 208000000097 Sertoli-Leydig cell tumor Diseases 0.000 claims description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 2
- 241000187747 Streptomyces Species 0.000 claims description 2
- 102100029538 Structural maintenance of chromosomes protein 1A Human genes 0.000 claims description 2
- 206010043276 Teratoma Diseases 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
- 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 claims description 2
- 208000015778 Undifferentiated pleomorphic sarcoma Diseases 0.000 claims description 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 2
- 235000009754 Vitis X bourquina Nutrition 0.000 claims description 2
- 235000012333 Vitis X labruscana Nutrition 0.000 claims description 2
- 240000006365 Vitis vinifera Species 0.000 claims description 2
- 235000014787 Vitis vinifera Nutrition 0.000 claims description 2
- 206010048215 Xanthomatosis Diseases 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
- 229960004176 aclarubicin Drugs 0.000 claims description 2
- 229930183665 actinomycin Natural products 0.000 claims description 2
- 210000004100 adrenal gland Anatomy 0.000 claims description 2
- 229960000473 altretamine Drugs 0.000 claims description 2
- 229960003896 aminopterin Drugs 0.000 claims description 2
- 229960002550 amrubicin Drugs 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
- 229940045799 anthracyclines and related substance 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
- 229960002756 azacitidine Drugs 0.000 claims description 2
- 125000003725 azepanyl group Chemical group 0.000 claims description 2
- 229960002707 bendamustine Drugs 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
- 208000026900 bile duct neoplasm Diseases 0.000 claims description 2
- 210000003445 biliary tract Anatomy 0.000 claims description 2
- 229960001561 bleomycin 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
- 210000000988 bone and bone Anatomy 0.000 claims description 2
- 201000011143 bone giant cell tumor Diseases 0.000 claims description 2
- 210000004556 brain Anatomy 0.000 claims description 2
- 210000000481 breast Anatomy 0.000 claims description 2
- 201000003149 breast fibroadenoma Diseases 0.000 claims description 2
- 210000003123 bronchiole Anatomy 0.000 claims description 2
- 201000002143 bronchus adenoma Diseases 0.000 claims description 2
- 229960002092 busulfan Drugs 0.000 claims description 2
- 229960004117 capecitabine Drugs 0.000 claims description 2
- 125000004432 carbon atom 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
- 210000003679 cervix uteri Anatomy 0.000 claims description 2
- 101150113535 chek1 gene Proteins 0.000 claims description 2
- HWGQMRYQVZSGDQ-HZPDHXFCSA-N chembl3137320 Chemical compound CN1N=CN=C1[C@H]([C@H](N1)C=2C=CC(F)=CC=2)C2=NNC(=O)C3=C2C1=CC(F)=C3 HWGQMRYQVZSGDQ-HZPDHXFCSA-N 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
- 201000005217 chondroblastoma Diseases 0.000 claims description 2
- 208000009060 clear cell adenocarcinoma Diseases 0.000 claims description 2
- 229960000928 clofarabine Drugs 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
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 claims description 2
- 229960004397 cyclophosphamide Drugs 0.000 claims description 2
- 208000031513 cyst Diseases 0.000 claims description 2
- 229960003901 dacarbazine Drugs 0.000 claims description 2
- 230000006378 damage Effects 0.000 claims description 2
- 229960000975 daunorubicin Drugs 0.000 claims description 2
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 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
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
- 229960004679 doxorubicin Drugs 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000002500 effect on skin Effects 0.000 claims description 2
- 210000002615 epidermis Anatomy 0.000 claims description 2
- 229960001904 epirubicin Drugs 0.000 claims description 2
- 208000010932 epithelial neoplasm Diseases 0.000 claims description 2
- 201000004101 esophageal cancer Diseases 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
- 201000010934 exostosis Diseases 0.000 claims description 2
- 230000001605 fetal effect Effects 0.000 claims description 2
- 239000000835 fiber Substances 0.000 claims description 2
- 229960000961 floxuridine Drugs 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
- 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
- 206010017758 gastric cancer Diseases 0.000 claims description 2
- 230000002496 gastric effect Effects 0.000 claims description 2
- 208000015419 gastrin-producing neuroendocrine tumor Diseases 0.000 claims description 2
- 201000000052 gastrinoma Diseases 0.000 claims description 2
- 230000026030 halogenation Effects 0.000 claims description 2
- 238000005658 halogenation reaction Methods 0.000 claims description 2
- 210000002216 heart Anatomy 0.000 claims description 2
- 208000006359 hepatoblastoma Diseases 0.000 claims description 2
- 201000002735 hepatocellular adenoma Diseases 0.000 claims description 2
- UUVWYPNAQBNQJQ-UHFFFAOYSA-N hexamethylmelamine Chemical compound CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 claims description 2
- 230000006801 homologous recombination Effects 0.000 claims description 2
- 238000002744 homologous recombination Methods 0.000 claims description 2
- 229960000908 idarubicin Drugs 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
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 2
- 201000004933 in situ carcinoma Diseases 0.000 claims description 2
- 229950002133 iniparib Drugs 0.000 claims description 2
- 206010022498 insulinoma Diseases 0.000 claims description 2
- 210000000936 intestine Anatomy 0.000 claims description 2
- 125000003965 isoxazolidinyl group Chemical group 0.000 claims description 2
- 210000001117 keloid Anatomy 0.000 claims description 2
- 210000003734 kidney Anatomy 0.000 claims description 2
- 208000022013 kidney Wilms tumor Diseases 0.000 claims description 2
- 210000002429 large intestine 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
- 201000007270 liver cancer Diseases 0.000 claims description 2
- 208000014018 liver neoplasm Diseases 0.000 claims description 2
- 229950008991 lobaplatin Drugs 0.000 claims description 2
- 229960002247 lomustine 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
- 229960000733 mannosulfan Drugs 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
- 208000023356 medullary thyroid gland carcinoma Diseases 0.000 claims description 2
- 229960001924 melphalan Drugs 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 meninge Anatomy 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
- 229960004857 mitomycin Drugs 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- 208000010492 mucinous cystadenocarcinoma Diseases 0.000 claims description 2
- 208000009091 myxoma Diseases 0.000 claims description 2
- 210000000653 nervous system Anatomy 0.000 claims description 2
- 208000007538 neurilemmoma Diseases 0.000 claims description 2
- 208000004649 neutrophil actin dysfunction Diseases 0.000 claims description 2
- 229960001420 nimustine Drugs 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
- PCHKPVIQAHNQLW-CQSZACIVSA-N niraparib 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
- OSTGTTZJOCZWJG-UHFFFAOYSA-N nitrosourea Chemical compound NC(=O)N=NO OSTGTTZJOCZWJG-UHFFFAOYSA-N 0.000 claims description 2
- 201000008482 osteoarthritis Diseases 0.000 claims description 2
- 208000008798 osteoma Diseases 0.000 claims description 2
- 210000001672 ovary Anatomy 0.000 claims description 2
- 210000003101 oviduct Anatomy 0.000 claims description 2
- 125000000160 oxazolidinyl group Chemical group 0.000 claims description 2
- 210000000496 pancreas Anatomy 0.000 claims description 2
- 201000008129 pancreatic ductal adenocarcinoma Diseases 0.000 claims description 2
- 208000021255 pancreatic insulinoma Diseases 0.000 claims description 2
- 208000007312 paraganglioma Diseases 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
- 229960002340 pentostatin Drugs 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 210000003800 pharynx Anatomy 0.000 claims description 2
- 208000028591 pheochromocytoma Diseases 0.000 claims description 2
- 230000026731 phosphorylation Effects 0.000 claims description 2
- 238000006366 phosphorylation reaction Methods 0.000 claims description 2
- 229950005566 picoplatin Drugs 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
- 229960001221 pirarubicin Drugs 0.000 claims description 2
- 229960004694 prednimustine Drugs 0.000 claims description 2
- 230000001737 promoting effect Effects 0.000 claims description 2
- 210000002307 prostate Anatomy 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 effect Effects 0.000 claims description 2
- 229960004432 raltitrexed Drugs 0.000 claims description 2
- 229960002185 ranimustine Drugs 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
- 229960003440 semustine Drugs 0.000 claims description 2
- 230000019491 signal transduction Effects 0.000 claims description 2
- 210000003491 skin Anatomy 0.000 claims description 2
- 210000003625 skull Anatomy 0.000 claims description 2
- 210000000813 small intestine Anatomy 0.000 claims description 2
- 210000002784 stomach Anatomy 0.000 claims description 2
- 201000011549 stomach cancer Diseases 0.000 claims description 2
- 229960001052 streptozocin Drugs 0.000 claims description 2
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin 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 cell Anatomy 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
- 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
- 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 claims description 2
- 208000001608 teratocarcinoma Diseases 0.000 claims description 2
- 210000001550 testis Anatomy 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
- 210000001685 thyroid gland Anatomy 0.000 claims description 2
- 208000030901 thyroid gland follicular carcinoma Diseases 0.000 claims description 2
- 208000030045 thyroid gland papillary carcinoma Diseases 0.000 claims description 2
- 229960003087 tioguanine Drugs 0.000 claims description 2
- MNRILEROXIRVNJ-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=NC=N[C]21 MNRILEROXIRVNJ-UHFFFAOYSA-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
- 190014017283 triplatin tetranitrate Chemical compound 0.000 claims description 2
- 229950002860 triplatin tetranitrate Drugs 0.000 claims description 2
- 208000022679 triple-negative breast carcinoma Diseases 0.000 claims description 2
- 229960000875 trofosfamide Drugs 0.000 claims description 2
- UMKFEPPTGMDVMI-UHFFFAOYSA-N trofosfamide Chemical compound ClCCN(CCCl)P1(=O)OCCCN1CCCl UMKFEPPTGMDVMI-UHFFFAOYSA-N 0.000 claims description 2
- 208000022271 tubular adenoma Diseases 0.000 claims description 2
- 229960001055 uracil mustard Drugs 0.000 claims description 2
- 210000003708 urethra Anatomy 0.000 claims description 2
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 2
- 210000004291 uterus Anatomy 0.000 claims description 2
- 210000001215 vagina Anatomy 0.000 claims description 2
- 229960000653 valrubicin Drugs 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
- 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
- 229950011257 veliparib Drugs 0.000 claims description 2
- 208000009540 villous adenoma Diseases 0.000 claims description 2
- 210000003905 vulva Anatomy 0.000 claims description 2
- 229960000641 zorubicin Drugs 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
- 239000012623 DNA damaging agent Substances 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 230000006698 induction Effects 0.000 claims 1
- 238000011275 oncology therapy Methods 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
- 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
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 239000003560 cancer drug Substances 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 208000014674 injury Diseases 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
- 229960003171 plicamycin Drugs 0.000 description 1
- 230000003389 potentiating effect 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 (enrdf_load_stackoverflow) | 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 (enrdf_load_stackoverflow) |
JP (1) | JP2016540773A (enrdf_load_stackoverflow) |
WO (1) | WO2015084384A1 (enrdf_load_stackoverflow) |
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 |
KR102678021B1 (ko) | 2015-09-30 | 2024-06-26 | 버텍스 파마슈티칼스 인코포레이티드 | Dna 손상제와 병용되는, atr 저해제를 포함하는 암 치료용 약제학적 조성물 |
EP3461480A1 (en) | 2017-09-27 | 2019-04-03 | Onxeo | Combination of a dna damage response cell cycle checkpoint inhibitors and belinostat for treating cancer |
ES3009674T3 (en) | 2018-09-26 | 2025-03-31 | Merck Patent Gmbh | Combination of a pd-1 antagonist, an atr inhibitor and a platinating agent for the treatment of cancer |
JP2022505041A (ja) | 2018-10-15 | 2022-01-14 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | Dnaアルキル化剤及びatr阻害剤を使用する併用療法 |
CN114369096A (zh) | 2020-10-16 | 2022-04-19 | 上海迪诺医药科技有限公司 | 三杂环衍生物、其药物组合物及应用 |
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 |
---|---|---|---|---|
US8044049B2 (en) * | 2006-08-04 | 2011-10-25 | Takeda Pharmaceutical Company Limited | Fused heterocyclic derivative and use thereof |
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 EP EP13811718.9A patent/EP3077393A1/en not_active Withdrawn
- 2013-12-06 JP JP2016536710A patent/JP2016540773A/ja active Pending
- 2013-12-06 WO PCT/US2013/073482 patent/WO2015084384A1/en active Application Filing