JP2015530975A5 - - Google Patents
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- Publication number
- JP2015530975A5 JP2015530975A5 JP2015524333A JP2015524333A JP2015530975A5 JP 2015530975 A5 JP2015530975 A5 JP 2015530975A5 JP 2015524333 A JP2015524333 A JP 2015524333A JP 2015524333 A JP2015524333 A JP 2015524333A JP 2015530975 A5 JP2015530975 A5 JP 2015530975A5
- Authority
- JP
- Japan
- Prior art keywords
- alkylene
- cycloalkyl
- heterocyclyl
- membered heteroaryl
- aryl
- 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.)
- Granted
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- 125000002947 alkylene group Chemical group 0.000 claims description 64
- 125000000623 heterocyclic group Chemical group 0.000 claims description 60
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 51
- 150000001875 compounds Chemical class 0.000 claims description 42
- 229910052731 fluorine Inorganic materials 0.000 claims description 30
- 229910052801 chlorine Inorganic materials 0.000 claims description 28
- 125000001424 substituent group Chemical group 0.000 claims description 27
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 26
- 229910052757 nitrogen Inorganic materials 0.000 claims description 23
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 20
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 20
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 16
- -1 Iburuchinibu Chemical compound 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 14
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 14
- 125000005842 heteroatom Chemical group 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 14
- 229910052805 deuterium Inorganic materials 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 8
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 125000001931 aliphatic group Chemical group 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 208000035475 disorder Diseases 0.000 claims description 6
- 230000002062 proliferating effect Effects 0.000 claims description 6
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 5
- 201000001320 Atherosclerosis Diseases 0.000 claims description 5
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 5
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 4
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 4
- 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 4
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical group 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
- 102000001253 Protein Kinase Human genes 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 239000012472 biological sample Substances 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 108060006633 protein kinase Proteins 0.000 claims description 4
- 108091008598 receptor tyrosine kinases Proteins 0.000 claims description 4
- 102000027426 receptor tyrosine kinases Human genes 0.000 claims description 4
- 229940124597 therapeutic agent Drugs 0.000 claims description 4
- 229960001350 tofacitinib Drugs 0.000 claims description 4
- UJLAWZDWDVHWOW-YPMHNXCESA-N tofacitinib Chemical compound C[C@@H]1CCN(C(=O)CC#N)C[C@@H]1N(C)C1=NC=NC2=C1C=CN2 UJLAWZDWDVHWOW-YPMHNXCESA-N 0.000 claims description 4
- 206010005003 Bladder cancer Diseases 0.000 claims description 3
- 206010006187 Breast cancer Diseases 0.000 claims description 3
- 208000026310 Breast neoplasm Diseases 0.000 claims description 3
- 206010009944 Colon cancer Diseases 0.000 claims description 3
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 3
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
- 208000014767 Myeloproliferative disease Diseases 0.000 claims description 3
- 201000007224 Myeloproliferative neoplasm Diseases 0.000 claims description 3
- 206010028980 Neoplasm Diseases 0.000 claims description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
- 206010060862 Prostate cancer Diseases 0.000 claims description 3
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 3
- 206010038389 Renal cancer Diseases 0.000 claims description 3
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 3
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 3
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 3
- 201000007455 central nervous system cancer Diseases 0.000 claims description 3
- 208000029742 colonic neoplasm Diseases 0.000 claims description 3
- 201000006585 gastric adenocarcinoma Diseases 0.000 claims description 3
- 208000005017 glioblastoma Diseases 0.000 claims description 3
- 125000001188 haloalkyl group Chemical group 0.000 claims description 3
- 201000010536 head and neck cancer Diseases 0.000 claims description 3
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 3
- 201000010982 kidney cancer Diseases 0.000 claims description 3
- 201000007270 liver cancer Diseases 0.000 claims description 3
- 208000014018 liver neoplasm Diseases 0.000 claims description 3
- 201000005202 lung cancer Diseases 0.000 claims description 3
- 208000020816 lung neoplasm Diseases 0.000 claims description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 3
- 208000037819 metastatic cancer Diseases 0.000 claims description 3
- 208000011575 metastatic malignant neoplasm Diseases 0.000 claims description 3
- 201000002528 pancreatic cancer Diseases 0.000 claims description 3
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 3
- 201000000849 skin cancer Diseases 0.000 claims description 3
- 201000002510 thyroid cancer Diseases 0.000 claims description 3
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 2
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 2
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 claims description 2
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 2
- ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 claims description 2
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 claims description 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 2
- 239000005517 L01XE01 - Imatinib Substances 0.000 claims description 2
- 239000005411 L01XE02 - Gefitinib Substances 0.000 claims description 2
- 239000005551 L01XE03 - Erlotinib Substances 0.000 claims description 2
- 239000002147 L01XE04 - Sunitinib Substances 0.000 claims description 2
- 239000005511 L01XE05 - Sorafenib Substances 0.000 claims description 2
- 239000002067 L01XE06 - Dasatinib Substances 0.000 claims description 2
- 239000002136 L01XE07 - Lapatinib Substances 0.000 claims description 2
- 239000005536 L01XE08 - Nilotinib Substances 0.000 claims description 2
- 239000003798 L01XE11 - Pazopanib Substances 0.000 claims description 2
- 239000002145 L01XE14 - Bosutinib Substances 0.000 claims description 2
- 239000002138 L01XE21 - Regorafenib Substances 0.000 claims description 2
- 239000002137 L01XE24 - Ponatinib Substances 0.000 claims description 2
- UCEQXRCJXIVODC-PMACEKPBSA-N LSM-1131 Chemical compound C1CCC2=CC=CC3=C2N1C=C3[C@@H]1C(=O)NC(=O)[C@H]1C1=CNC2=CC=CC=C12 UCEQXRCJXIVODC-PMACEKPBSA-N 0.000 claims description 2
- 150000001204 N-oxides Chemical class 0.000 claims description 2
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 claims description 2
- CBPNZQVSJQDFBE-FUXHJELOSA-N Temsirolimus Chemical compound C1C[C@@H](OC(=O)C(C)(CO)CO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 CBPNZQVSJQDFBE-FUXHJELOSA-N 0.000 claims description 2
- 239000004012 Tofacitinib Substances 0.000 claims description 2
- 108091008605 VEGF receptors Proteins 0.000 claims description 2
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims description 2
- 229940009456 adriamycin Drugs 0.000 claims description 2
- 229960001686 afatinib Drugs 0.000 claims description 2
- ULXXDDBFHOBEHA-CWDCEQMOSA-N afatinib Chemical compound N1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC1=CC=C(F)C(Cl)=C1 ULXXDDBFHOBEHA-CWDCEQMOSA-N 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 230000001028 anti-proliverative effect Effects 0.000 claims description 2
- 239000002246 antineoplastic agent Substances 0.000 claims description 2
- 229960003005 axitinib Drugs 0.000 claims description 2
- RITAVMQDGBJQJZ-FMIVXFBMSA-N axitinib Chemical compound CNC(=O)C1=CC=CC=C1SC1=CC=C(C(\C=C\C=2N=CC=CC=2)=NN2)C2=C1 RITAVMQDGBJQJZ-FMIVXFBMSA-N 0.000 claims description 2
- 229960003270 belimumab Drugs 0.000 claims description 2
- 229960000397 bevacizumab Drugs 0.000 claims description 2
- 229960003736 bosutinib Drugs 0.000 claims description 2
- UBPYILGKFZZVDX-UHFFFAOYSA-N bosutinib Chemical compound C1=C(Cl)C(OC)=CC(NC=2C3=CC(OC)=C(OCCCN4CCN(C)CC4)C=C3N=CC=2C#N)=C1Cl UBPYILGKFZZVDX-UHFFFAOYSA-N 0.000 claims description 2
- 229960000455 brentuximab vedotin Drugs 0.000 claims description 2
- 229960005395 cetuximab Drugs 0.000 claims description 2
- 229960004397 cyclophosphamide Drugs 0.000 claims description 2
- 229940127089 cytotoxic agent Drugs 0.000 claims description 2
- 229960002448 dasatinib Drugs 0.000 claims description 2
- 125000004431 deuterium atom Chemical group 0.000 claims description 2
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 claims description 2
- 229960003957 dexamethasone Drugs 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000000694 effects Effects 0.000 claims description 2
- 229960001433 erlotinib Drugs 0.000 claims description 2
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 claims description 2
- 229960005420 etoposide Drugs 0.000 claims description 2
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 claims description 2
- 229960005167 everolimus Drugs 0.000 claims description 2
- 229960002949 fluorouracil Drugs 0.000 claims description 2
- 229960002584 gefitinib Drugs 0.000 claims description 2
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 claims description 2
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims description 2
- 229960005277 gemcitabine Drugs 0.000 claims description 2
- 229960000578 gemtuzumab Drugs 0.000 claims description 2
- 229960002411 imatinib Drugs 0.000 claims description 2
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 claims description 2
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- 229960005386 ipilimumab Drugs 0.000 claims description 2
- 229960002014 ixabepilone Drugs 0.000 claims description 2
- FABUFPQFXZVHFB-CFWQTKTJSA-N ixabepilone Chemical compound C/C([C@@H]1C[C@@H]2O[C@]2(C)CCC[C@@H]([C@@H]([C@H](C)C(=O)C(C)(C)[C@H](O)CC(=O)N1)O)C)=C\C1=CSC(C)=N1 FABUFPQFXZVHFB-CFWQTKTJSA-N 0.000 claims description 2
- 229960004891 lapatinib Drugs 0.000 claims description 2
- BCFGMOOMADDAQU-UHFFFAOYSA-N lapatinib Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 BCFGMOOMADDAQU-UHFFFAOYSA-N 0.000 claims description 2
- 229960003784 lenvatinib Drugs 0.000 claims description 2
- WOSKHXYHFSIKNG-UHFFFAOYSA-N lenvatinib Chemical compound C=12C=C(C(N)=O)C(OC)=CC2=NC=CC=1OC(C=C1Cl)=CC=C1NC(=O)NC1CC1 WOSKHXYHFSIKNG-UHFFFAOYSA-N 0.000 claims description 2
- 239000002207 metabolite Substances 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 229950003968 motesanib Drugs 0.000 claims description 2
- RAHBGWKEPAQNFF-UHFFFAOYSA-N motesanib Chemical compound C=1C=C2C(C)(C)CNC2=CC=1NC(=O)C1=CC=CN=C1NCC1=CC=NC=C1 RAHBGWKEPAQNFF-UHFFFAOYSA-N 0.000 claims description 2
- 229950008835 neratinib Drugs 0.000 claims description 2
- ZNHPZUKZSNBOSQ-BQYQJAHWSA-N neratinib Chemical compound C=12C=C(NC\C=C\CN(C)C)C(OCC)=CC2=NC=C(C#N)C=1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZNHPZUKZSNBOSQ-BQYQJAHWSA-N 0.000 claims description 2
- 229960001346 nilotinib Drugs 0.000 claims description 2
- HHZIURLSWUIHRB-UHFFFAOYSA-N nilotinib Chemical compound C1=NC(C)=CN1C1=CC(NC(=O)C=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 HHZIURLSWUIHRB-UHFFFAOYSA-N 0.000 claims description 2
- 229960002450 ofatumumab Drugs 0.000 claims description 2
- 229960000572 olaparib Drugs 0.000 claims description 2
- 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 2
- 229960001972 panitumumab Drugs 0.000 claims description 2
- 229960000639 pazopanib Drugs 0.000 claims description 2
- CUIHSIWYWATEQL-UHFFFAOYSA-N pazopanib Chemical compound C1=CC2=C(C)N(C)N=C2C=C1N(C)C(N=1)=CC=NC=1NC1=CC=C(C)C(S(N)(=O)=O)=C1 CUIHSIWYWATEQL-UHFFFAOYSA-N 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 229960001131 ponatinib Drugs 0.000 claims description 2
- PHXJVRSECIGDHY-UHFFFAOYSA-N ponatinib Chemical compound C1CN(C)CCN1CC(C(=C1)C(F)(F)F)=CC=C1NC(=O)C1=CC=C(C)C(C#CC=2N3N=CC=CC3=NC=2)=C1 PHXJVRSECIGDHY-UHFFFAOYSA-N 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 229940002612 prodrug Drugs 0.000 claims description 2
- 239000000651 prodrug Substances 0.000 claims description 2
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- 229960004836 regorafenib Drugs 0.000 claims description 2
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- 239000003981 vehicle Substances 0.000 claims description 2
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- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims description 2
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims description 2
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| US20150299219A1 (en) * | 2014-04-22 | 2015-10-22 | Calitor Sciences, Llc | Bicyclic pyrazolone compounds and methods of use |
| WO2016061231A1 (en) * | 2014-10-14 | 2016-04-21 | Deciphera Pharmaceuticals, Llc | Inhibition of tumor cell interactions with the microenvironment resulting in a reduction in tumor growth and disease progression |
| CN106467541B (zh) | 2015-08-18 | 2019-04-05 | 暨南大学 | 取代喹诺酮类衍生物或其药学上可接受的盐或立体异构体及其药用组合物和应用 |
| CN105153026B (zh) * | 2015-08-21 | 2018-02-02 | 江西科技师范大学 | 含联芳基酰胺结构的索拉非尼衍生物及其制备方法和应用 |
| CN105237523B (zh) * | 2015-10-08 | 2018-06-01 | 深圳市博圣康生物科技有限公司 | 嘧啶衍生物及其制备方法、用途 |
| CA3014769C (en) | 2016-03-02 | 2024-01-09 | Medivir Aktiebolag | Combination therapy with sorafenib or regorafenib and a phosphoramidate prodrug of troxacitabine |
| AR108107A1 (es) * | 2016-04-29 | 2018-07-18 | Syngenta Participations Ag | Proceso para preparar compuestos herbicidas |
| US10538478B2 (en) | 2016-10-10 | 2020-01-21 | Basf Se | Catalyst modification with alkali metal, alkaline earth metal or rare earth metal ions in the continuous liquid-phase hydrogenation of nitro compounds |
| ES2928773T3 (es) | 2017-01-17 | 2022-11-22 | Heparegenix Gmbh | Inhibidores de proteína cinasas para fomentar la regeneración hepática o reducir o prevenir la muerte de hepatocitos |
| WO2019228252A1 (zh) | 2018-06-01 | 2019-12-05 | 杭州阿诺生物医药科技有限公司 | 一种高活性csf1r抑制剂化合物 |
| CN109096250A (zh) * | 2018-09-25 | 2018-12-28 | 辽宁大学 | 含哒嗪酮的4-苯氧基吡啶类化合物及其应用 |
| CA3121202A1 (en) | 2018-11-30 | 2020-06-04 | Nuvation Bio Inc. | Pyrrole and pyrazole compounds and methods of use thereof |
| JP7293404B2 (ja) * | 2019-05-24 | 2023-06-19 | メッドシャイン ディスカバリー インコーポレイテッド | ｃ－ＭＥＴ／ＡＸＬ阻害剤の結晶形 |
| JP2023507816A (ja) * | 2019-12-20 | 2023-02-27 | エンジン バイオサイエンシズ プライベート リミテッド | がんを治療するための方法及び組成物 |
| BR112022019517A2 (pt) | 2020-03-30 | 2022-12-06 | Hutchison Medipharma Ltd | Compostos de amida e usos dos mesmos |
| WO2022007921A1 (zh) | 2020-07-10 | 2022-01-13 | 北京范恩柯尔生物科技有限公司 | 三嗪类化合物及其组合物和用途 |
| KR20220170766A (ko) * | 2021-06-22 | 2022-12-30 | 주식회사 엘지화학 | 단백질 키나아제 억제제로서의 신규한 화합물 |
| TW202315628A (zh) * | 2021-06-24 | 2023-04-16 | 南韓商Ｌｇ化學股份有限公司 | 作為ｒｏｎ抑制劑之新穎吡啶衍生物化合物 |
| CN114213404B (zh) * | 2021-12-27 | 2024-08-06 | 武汉九州钰民医药科技有限公司 | Vegfr抑制剂替沃扎尼的合成工艺 |
| CN114796227B (zh) * | 2022-05-30 | 2023-12-01 | 中山大学 | Ponatinib在制备预防或治疗血管退行性疾病药物中的应用及该药物 |
| CN114903996B (zh) * | 2022-06-22 | 2023-10-20 | 武汉大学中南医院 | Hedgehog通路的特异性抑制剂在制备用于治疗宫腔粘连的药物中的应用 |
| KR20240101434A (ko) * | 2022-12-23 | 2024-07-02 | 주식회사 엘지화학 | Ron 억제제로서 신규한 화합물 |
| CN116283920B (zh) * | 2023-03-31 | 2024-04-16 | 贵州医科大学 | 2,4-二取代吡啶类化合物及其应用 |
Family Cites Families (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR901228A (fr) | 1943-01-16 | 1945-07-20 | Deutsche Edelstahlwerke Ag | Système d'aimant à entrefer annulaire |
| US5304121A (en) | 1990-12-28 | 1994-04-19 | Boston Scientific Corporation | Drug delivery system making use of a hydrogel polymer coating |
| US5886026A (en) | 1993-07-19 | 1999-03-23 | Angiotech Pharmaceuticals Inc. | Anti-angiogenic compositions and methods of use |
| EP0734436B1 (en) | 1993-11-30 | 1999-04-14 | McGILL UNIVERSITY | Inhibition of dna methyltransferase |
| US5578716A (en) | 1993-12-01 | 1996-11-26 | Mcgill University | DNA methyltransferase antisense oligonucleotides |
| US6099562A (en) | 1996-06-13 | 2000-08-08 | Schneider (Usa) Inc. | Drug coating with topcoat |
| US6268137B1 (en) | 1996-05-22 | 2001-07-31 | Methylgene, Inc. | Specific inhibitors of DNA methyl transferase |
| WO1998054313A2 (en) | 1997-05-30 | 1998-12-03 | Mcgill University | Dna methyltransferase genomic sequences and antisense oligonucleotides |
| US6020318A (en) | 1997-05-30 | 2000-02-01 | Methylgene, Inc. | DNA methyltransferase genomic sequences and antisense oligonucleotides |
| US6066625A (en) | 1998-02-03 | 2000-05-23 | Methylgene, Inc. | Optimized antisense oligonucleotides complementary to DNA methyltransferase sequences |
| US6953783B1 (en) | 1998-10-19 | 2005-10-11 | Methylgene, Inc. | Modulation of gene expression by combination therapy |
| WO2000071703A2 (en) | 1999-05-03 | 2000-11-30 | Methylgene Inc. | Inhibition of histone deacetylase |
| EP1748046A3 (en) | 1999-11-23 | 2007-08-22 | Methylgene, Inc. | Inhibitors of histone deacetylase |
| WO2001070675A2 (en) | 2000-03-24 | 2001-09-27 | Methylgene, Inc. | Inhibitors of histone deacetylase |
| EP2093292A2 (en) | 2000-03-24 | 2009-08-26 | Methylgene, Inc. | Inhibition of specific histone deacetylase isoforms |
| CN101851173A (zh) | 2001-09-14 | 2010-10-06 | 梅特希尔基因公司 | 组蛋白脱乙酰化酶抑制剂 |
| US7868204B2 (en) | 2001-09-14 | 2011-01-11 | Methylgene Inc. | Inhibitors of histone deacetylase |
| US6897220B2 (en) | 2001-09-14 | 2005-05-24 | Methylgene, Inc. | Inhibitors of histone deacetylase |
| AU2003273701A1 (en) | 2002-10-17 | 2004-05-04 | Methylgene Inc. | Inhibitors of histone deacetylase |
| WO2005030705A1 (en) | 2003-09-24 | 2005-04-07 | Methylgene, Inc. | Inhibitors of histone deacetylase |
| KR20060118472A (ko) * | 2003-10-16 | 2006-11-23 | 카이론 코포레이션 | 치환 벤자졸 및 ｒａｆ 키나아제의 저해제로서 그것의 사용 |
| MXPA06010900A (es) | 2004-03-26 | 2007-02-21 | Methylgene Inc | Inhibidores de histona desacetilasa. |
| US7459562B2 (en) | 2004-04-23 | 2008-12-02 | Bristol-Myers Squibb Company | Monocyclic heterocycles as kinase inhibitors |
| ES2438017T3 (es) | 2004-07-30 | 2014-01-15 | Methylgene Inc. | Inhibidores de la señalización del receptor del VEGF y del receptor del HGF |
| JO2787B1 (en) * | 2005-04-27 | 2014-03-15 | امجين إنك, | Alternative amide derivatives and methods of use |
| WO2008046216A1 (en) | 2006-10-18 | 2008-04-24 | Methylgene, Inc. | Kinase inhibitors and uses thereof |
| SI2089364T1 (sl) | 2006-11-08 | 2013-10-30 | Bristol-Myers Squibb Company | Spojine piridinona |
| JP5693239B2 (ja) | 2008-01-23 | 2015-04-01 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | ４−ピリジノン化合物および癌についてのその使用 |
| BRPI0906444B8 (pt) | 2008-01-23 | 2021-05-25 | Bristol Myers Squibb Co | compostos de 4-piridinona, composição farmacêutica que os compreende, bem como uso dos mesmos |
| WO2009108670A1 (en) | 2008-02-28 | 2009-09-03 | Merck Serono S.A. | Protein kinase inhibitors and use thereof |
| AU2009246263B2 (en) * | 2008-05-14 | 2014-08-21 | Amgen Inc. | Combinations VEGF(R) inhibitors and hepatocyte growth factor (c-Met) inhibitors for the treatment of cancer |
| JP2012504606A (ja) * | 2008-10-01 | 2012-02-23 | ラディック インスティテュート フォー キャンサー リサーチ | 癌の治療方法 |
| ES2599458T3 (es) * | 2008-10-14 | 2017-02-01 | Sunshine Lake Pharma Co., Ltd. | Compuestos y métodos de uso |
| KR100961410B1 (ko) * | 2008-10-14 | 2010-06-09 | (주)네오팜 | 단백질 키나제 억제제로서 헤테로사이클릭 화합물 |
| EP2408300B1 (en) | 2009-03-21 | 2016-05-11 | Sunshine Lake Pharma Co., Ltd. | Amino ester derivatives, salts thereof and methods of use |
| CN102573994B (zh) | 2009-08-06 | 2015-06-24 | 默克专利有限公司 | 双环脲化合物 |
| CN102140093A (zh) | 2010-02-03 | 2011-08-03 | 上海源力生物技术有限公司 | 吡啶酮酰胺类衍生物、其制备方法及其在医药上的应用 |
| CA2800998A1 (en) | 2010-04-29 | 2011-11-10 | Deciphera Pharmaceuticals, Llc | Pyridone amides and analogs exhibiting anti-cancer and anti-proliferative activities |
| ES2598530T3 (es) | 2010-07-14 | 2017-01-27 | Betta Pharmaceuticals Co., Ltd. | Nuevos derivados heterocíclicos condensados útiles como inhibidores de la tirosina quinasa c-Met |
| EA201300283A1 (ru) | 2010-08-27 | 2013-08-30 | Мерк Патент Гмбх | Производные фуропиридина |
| US20140057908A1 (en) * | 2010-09-27 | 2014-02-27 | Exelixis, Inc. | Method of Treating Cancer |
| RU2568258C2 (ru) | 2011-02-28 | 2015-11-20 | Саншайн Лейк Фарма Ко., Лтд | Замещенные соединения хинолина и способы их использования |
| CN102816175B (zh) | 2011-06-09 | 2015-12-16 | 上海汇伦生命科技有限公司 | 一种杂环并吡啶酮类化合物,其中间体、制备方法和用途 |
| EP2739143B1 (en) | 2011-08-05 | 2018-07-11 | Gary A. Flynn | Preparation and methods of use for ortho-aryl 5- membered heteroaryl-carboxamide containing multi-targeted kinase inhibitors |
| JP2015507606A (ja) | 2011-11-22 | 2015-03-12 | デシフェラ ファーマシューティカルズ，エルエルシー | 抗癌および抗増殖作用を示すピリドンアミドおよび類似体 |
| WO2013180949A1 (en) | 2012-05-27 | 2013-12-05 | Ning Xi | Substituted quinoline compounds and methods of use |
| JP6342392B2 (ja) * | 2012-07-28 | 2018-06-13 | カリター・サイエンシーズ・エルエルシー | 置換型ピラゾロン化合物及び使用方法 |
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