CN115650985B - 作为ret激酶抑制剂的杂环化合物 - Google Patents
作为ret激酶抑制剂的杂环化合物 Download PDFInfo
- Publication number
- CN115650985B CN115650985B CN202211269931.2A CN202211269931A CN115650985B CN 115650985 B CN115650985 B CN 115650985B CN 202211269931 A CN202211269931 A CN 202211269931A CN 115650985 B CN115650985 B CN 115650985B
- Authority
- CN
- China
- Prior art keywords
- alkyl
- amino
- hydrogen
- pyrazolo
- pharmaceutically acceptable
- 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.)
- Active
Links
- 102100028286 Proto-oncogene tyrosine-protein kinase receptor Ret Human genes 0.000 title claims 10
- 229940043355 kinase inhibitor Drugs 0.000 title description 8
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 8
- 150000002391 heterocyclic compounds Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 302
- 230000000694 effects Effects 0.000 claims abstract description 54
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 41
- 201000011510 cancer Diseases 0.000 claims abstract description 34
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 26
- 125000000217 alkyl group Chemical group 0.000 claims description 402
- 229910052739 hydrogen Inorganic materials 0.000 claims description 233
- 239000001257 hydrogen Substances 0.000 claims description 233
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 174
- 125000001424 substituent group Chemical group 0.000 claims description 134
- 125000005843 halogen group Chemical group 0.000 claims description 126
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 124
- 150000003839 salts Chemical class 0.000 claims description 111
- 125000000623 heterocyclic group Chemical group 0.000 claims description 102
- 125000001188 haloalkyl group Chemical group 0.000 claims description 85
- 125000003545 alkoxy group Chemical group 0.000 claims description 83
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 41
- 125000002947 alkylene group Chemical group 0.000 claims description 37
- 238000001727 in vivo Methods 0.000 claims description 19
- 208000023356 medullary thyroid gland carcinoma Diseases 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 9
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 9
- 238000000338 in vitro Methods 0.000 claims description 8
- 230000035772 mutation Effects 0.000 claims description 8
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 7
- 230000004663 cell proliferation Effects 0.000 claims description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- 208000009018 Medullary thyroid cancer Diseases 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 230000002255 enzymatic effect Effects 0.000 claims description 4
- 210000004881 tumor cell Anatomy 0.000 claims description 4
- 230000004927 fusion Effects 0.000 claims description 3
- 230000005945 translocation Effects 0.000 claims description 3
- 206010027476 Metastases Diseases 0.000 claims description 2
- 230000006907 apoptotic process Effects 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 208000032839 leukemia Diseases 0.000 claims description 2
- 230000009401 metastasis Effects 0.000 claims description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 2
- 201000005202 lung cancer Diseases 0.000 claims 2
- 208000020816 lung neoplasm Diseases 0.000 claims 2
- 208000003174 Brain Neoplasms Diseases 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 206010033128 Ovarian cancer Diseases 0.000 claims 1
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 1
- 208000000453 Skin Neoplasms Diseases 0.000 claims 1
- 230000033115 angiogenesis Effects 0.000 claims 1
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- 230000004709 cell invasion Effects 0.000 claims 1
- 208000029742 colonic neoplasm Diseases 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 201000007270 liver cancer Diseases 0.000 claims 1
- 208000014018 liver neoplasm Diseases 0.000 claims 1
- 230000036210 malignancy Effects 0.000 claims 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 1
- 201000000849 skin cancer Diseases 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 108
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 44
- 238000011282 treatment Methods 0.000 abstract description 42
- 108091000080 Phosphotransferase Proteins 0.000 abstract description 32
- 102000020233 phosphotransferase Human genes 0.000 abstract description 32
- 239000003112 inhibitor Substances 0.000 abstract description 27
- 201000010099 disease Diseases 0.000 abstract description 15
- 230000002062 proliferating effect Effects 0.000 abstract description 15
- 230000008569 process Effects 0.000 abstract description 4
- 238000001890 transfection Methods 0.000 abstract description 4
- 230000008707 rearrangement Effects 0.000 abstract description 3
- -1 cyano, hydroxy, carboxy, carbamoyl Chemical group 0.000 description 198
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 134
- 125000001072 heteroaryl group Chemical group 0.000 description 93
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 91
- 239000000203 mixture Substances 0.000 description 86
- 125000004438 haloalkoxy group Chemical group 0.000 description 83
- 125000003118 aryl group Chemical group 0.000 description 82
- 239000012453 solvate Substances 0.000 description 81
- 229910052757 nitrogen Inorganic materials 0.000 description 71
- 235000019439 ethyl acetate Nutrition 0.000 description 67
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 66
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 56
- 125000003282 alkyl amino group Chemical group 0.000 description 54
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 52
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 51
- 125000000392 cycloalkenyl group Chemical group 0.000 description 49
- 239000000543 intermediate Substances 0.000 description 48
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 47
- 239000007787 solid Substances 0.000 description 46
- 239000000243 solution Substances 0.000 description 41
- 125000004093 cyano group Chemical group *C#N 0.000 description 39
- 229910052760 oxygen Inorganic materials 0.000 description 38
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 35
- 239000002904 solvent Substances 0.000 description 34
- 229910052717 sulfur Inorganic materials 0.000 description 29
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 29
- 238000005160 1H NMR spectroscopy Methods 0.000 description 28
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 28
- 229910052799 carbon Inorganic materials 0.000 description 28
- 208000035475 disorder Diseases 0.000 description 28
- 238000000746 purification Methods 0.000 description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- 239000012267 brine Substances 0.000 description 27
- 125000005842 heteroatom Chemical group 0.000 description 27
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 27
- 125000000304 alkynyl group Chemical group 0.000 description 26
- 239000012043 crude product Substances 0.000 description 25
- 239000000284 extract Substances 0.000 description 25
- 238000004128 high performance liquid chromatography Methods 0.000 description 25
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 24
- 210000004027 cell Anatomy 0.000 description 23
- 238000006243 chemical reaction Methods 0.000 description 22
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 21
- 229940002612 prodrug Drugs 0.000 description 21
- 239000000651 prodrug Substances 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
- 229920006395 saturated elastomer Polymers 0.000 description 20
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 19
- 150000002431 hydrogen Chemical group 0.000 description 19
- 125000004433 nitrogen atom Chemical group N* 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- 239000000463 material Substances 0.000 description 17
- 239000000725 suspension Substances 0.000 description 17
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 16
- 125000004663 dialkyl amino group Chemical group 0.000 description 16
- 230000002401 inhibitory effect Effects 0.000 description 16
- 125000006239 protecting group Chemical group 0.000 description 16
- 125000004103 aminoalkyl group Chemical group 0.000 description 14
- 150000002148 esters Chemical class 0.000 description 14
- 238000003786 synthesis reaction Methods 0.000 description 14
- 239000010410 layer Substances 0.000 description 13
- 229960005419 nitrogen Drugs 0.000 description 13
- 230000005764 inhibitory process Effects 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 11
- 239000012044 organic layer Substances 0.000 description 11
- 125000003342 alkenyl group Chemical group 0.000 description 10
- 239000008346 aqueous phase Substances 0.000 description 10
- 238000003556 assay Methods 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- 238000002560 therapeutic procedure Methods 0.000 description 10
- 125000002252 acyl group Chemical group 0.000 description 9
- BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Substances OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 8
- 208000037196 Medullary thyroid carcinoma Diseases 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- 150000001408 amides Chemical class 0.000 description 8
- 230000000259 anti-tumor effect Effects 0.000 description 8
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 8
- 239000000460 chlorine Substances 0.000 description 8
- 150000002430 hydrocarbons Chemical group 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- 239000011593 sulfur Chemical group 0.000 description 8
- 208000013818 thyroid gland medullary carcinoma Diseases 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
- 150000001204 N-oxides Chemical class 0.000 description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 7
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical class [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 7
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
- 230000001028 anti-proliverative effect Effects 0.000 description 7
- 125000002619 bicyclic group Chemical group 0.000 description 7
- 239000012455 biphasic mixture Substances 0.000 description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 7
- 125000001715 oxadiazolyl group Chemical group 0.000 description 7
- 125000002971 oxazolyl group Chemical group 0.000 description 7
- 238000002953 preparative HPLC Methods 0.000 description 7
- 230000000717 retained effect Effects 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- 125000003831 tetrazolyl group Chemical group 0.000 description 7
- 125000001425 triazolyl group Chemical group 0.000 description 7
- JPKMVXLPXRWJMH-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-methyl-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC)C(C)(C)C JPKMVXLPXRWJMH-UHFFFAOYSA-N 0.000 description 6
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 125000003277 amino group Chemical group 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 6
- 125000004122 cyclic group Chemical group 0.000 description 6
- 125000002883 imidazolyl group Chemical group 0.000 description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 125000003226 pyrazolyl group Chemical group 0.000 description 6
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 5
- HZTDCOHZKXSXBA-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1)C(=O)NC)C(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1)C(=O)NC)C(C)(C)C HZTDCOHZKXSXBA-UHFFFAOYSA-N 0.000 description 5
- HKSZYXFMRVEQGF-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1)C(=O)NC)C(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1)C(=O)NC)C(C)C HKSZYXFMRVEQGF-UHFFFAOYSA-N 0.000 description 5
- LRVFBQIOCULFNX-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1)C(=O)NC1=NN(C=C1)C)C(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1)C(=O)NC1=NN(C=C1)C)C(C)(C)C LRVFBQIOCULFNX-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 238000002512 chemotherapy Methods 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 150000004677 hydrates Chemical class 0.000 description 5
- 230000002209 hydrophobic effect Effects 0.000 description 5
- 239000001301 oxygen Chemical group 0.000 description 5
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 5
- 125000003373 pyrazinyl group Chemical group 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 125000004076 pyridyl group Chemical group 0.000 description 5
- 125000000168 pyrrolyl group Chemical group 0.000 description 5
- 238000010189 synthetic method Methods 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 125000000335 thiazolyl group Chemical group 0.000 description 5
- KHWXTXSKIPRCHN-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-1-methylindole-6-carboxylic acid Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1N(C2=CC(=CC=C2C=1)C(=O)O)C)C(C)(C)C KHWXTXSKIPRCHN-UHFFFAOYSA-N 0.000 description 4
- OGUFXWBZNKEOCD-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-bromo-N-methyl-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Br)C(=O)NC)C(C)(C)C OGUFXWBZNKEOCD-UHFFFAOYSA-N 0.000 description 4
- ZWNXAOSIOZQDJI-UHFFFAOYSA-N 2-(4-amino-7-propan-2-ylpyrrolo[2,3-d]pyrimidin-5-yl)-3-chloro-N-methyl-1H-indole-6-carboxamide Chemical compound NC=1C2=C(N=CN=1)N(C=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC)C(C)C ZWNXAOSIOZQDJI-UHFFFAOYSA-N 0.000 description 4
- BYSACNLCTNNHPN-UHFFFAOYSA-N 2-(4-amino-7-propan-2-ylpyrrolo[2,3-d]pyrimidin-5-yl)-N-methyl-1H-indole-6-carboxamide Chemical compound CNC(=O)c1ccc2cc([nH]c2c1)-c1cn(C(C)C)c2ncnc(N)c12 BYSACNLCTNNHPN-UHFFFAOYSA-N 0.000 description 4
- BQUHSWVUQMWBKQ-UHFFFAOYSA-N 2-(8-amino-3-propan-2-ylimidazo[1,5-a]pyrazin-1-yl)-3-chloro-N-methyl-1H-indole-6-carboxamide Chemical compound NC=1C=2N(C=CN=1)C(=NC=2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC)C(C)C BQUHSWVUQMWBKQ-UHFFFAOYSA-N 0.000 description 4
- GZQVGSRUUTUJNG-UHFFFAOYSA-N 3-bromo-2h-pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound NC1=NC=NC2=NNC(Br)=C12 GZQVGSRUUTUJNG-UHFFFAOYSA-N 0.000 description 4
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 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 description 4
- 102000001301 EGF receptor Human genes 0.000 description 4
- 108060006698 EGF receptor Proteins 0.000 description 4
- WQTOJCOBZONGBQ-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC)C(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC)C(C)C WQTOJCOBZONGBQ-UHFFFAOYSA-N 0.000 description 4
- CPVUKZPQBGQJTP-UHFFFAOYSA-N NC1=NC=CC2=C1C(=NN2C(C)C)C=1NC2=CC(=CC=C2C=1)C(=O)NC Chemical compound NC1=NC=CC2=C1C(=NN2C(C)C)C=1NC2=CC(=CC=C2C=1)C(=O)NC CPVUKZPQBGQJTP-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 230000002159 abnormal effect Effects 0.000 description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 150000003973 alkyl amines Chemical class 0.000 description 4
- 235000011114 ammonium hydroxide Nutrition 0.000 description 4
- 125000003435 aroyl group Chemical group 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 238000009510 drug design Methods 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 235000019253 formic acid Nutrition 0.000 description 4
- 238000007429 general method Methods 0.000 description 4
- 239000003102 growth factor Substances 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 230000000155 isotopic effect Effects 0.000 description 4
- 125000002950 monocyclic group Chemical group 0.000 description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- 125000001113 thiadiazolyl group Chemical group 0.000 description 4
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 4
- UHTHHESEBZOYNR-UHFFFAOYSA-N vandetanib Chemical compound COC1=CC(C(/N=CN2)=N/C=3C(=CC(Br)=CC=3)F)=C2C=C1OCC1CCN(C)CC1 UHTHHESEBZOYNR-UHFFFAOYSA-N 0.000 description 4
- 239000003643 water by type Substances 0.000 description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 3
- DSKWNVPCROYIQW-UHFFFAOYSA-N 2-(4-amino-1-cyclobutylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-methyl-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC)C1CCC1 DSKWNVPCROYIQW-UHFFFAOYSA-N 0.000 description 3
- JATHVEVHCNBUNG-UHFFFAOYSA-N 2-(4-amino-1-cyclohexylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-methyl-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC)C1CCCCC1 JATHVEVHCNBUNG-UHFFFAOYSA-N 0.000 description 3
- QBXTYIQNVFGQQN-UHFFFAOYSA-N 2-(4-amino-1-propan-2-ylpyrazolo[4,3-c]pyridin-3-yl)-3-chloro-N-methyl-1H-indole-6-carboxamide Chemical compound NC1=NC=CC2=C1C(=NN2C(C)C)C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC QBXTYIQNVFGQQN-UHFFFAOYSA-N 0.000 description 3
- JENIHZJYWBWMAT-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-1H-indole-6-carboxylic acid Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)O)C(C)(C)C JENIHZJYWBWMAT-UHFFFAOYSA-N 0.000 description 3
- XKSROQSJCOMSFN-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-(2-hydroxyethyl)-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NCCO)C(C)(C)C XKSROQSJCOMSFN-UHFFFAOYSA-N 0.000 description 3
- GATYLOYCUAPWMB-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-(2-morpholin-4-ylethyl)-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NCCN1CCOCC1)C(C)(C)C GATYLOYCUAPWMB-UHFFFAOYSA-N 0.000 description 3
- MJSDVPHVJFPGEB-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-(3-piperidin-1-ylpropyl)-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NCCCN1CCCCC1)C(C)(C)C MJSDVPHVJFPGEB-UHFFFAOYSA-N 0.000 description 3
- ACNNJWMMLBYERQ-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-[1-(2-hydroxyethyl)pyrazol-3-yl]-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC1=NN(C=C1)CCO)C(C)(C)C ACNNJWMMLBYERQ-UHFFFAOYSA-N 0.000 description 3
- RAKDOBWGYQVOPT-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-[1-(2-methoxyethyl)pyrazol-3-yl]-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC1=NN(C=C1)CCOC)C(C)(C)C RAKDOBWGYQVOPT-UHFFFAOYSA-N 0.000 description 3
- XEDLQHAQDJOFQI-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-[1-(2-morpholin-4-ylethyl)pyrazol-3-yl]-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC1=NN(C=C1)CCN1CCOCC1)C(C)(C)C XEDLQHAQDJOFQI-UHFFFAOYSA-N 0.000 description 3
- ZLLYPULBPHUOLR-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-[1-[2-(dimethylamino)ethyl]pyrazol-3-yl]-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC1=NN(C=C1)CCN(C)C)C(C)(C)C ZLLYPULBPHUOLR-UHFFFAOYSA-N 0.000 description 3
- CDNJXEIHIBWNAM-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-[2-(2-morpholin-4-ylethoxy)ethyl]-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NCCOCCN1CCOCC1)C(C)(C)C CDNJXEIHIBWNAM-UHFFFAOYSA-N 0.000 description 3
- FFPFOCJSSHPGFQ-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-cyclopropyl-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC1CC1)C(C)(C)C FFPFOCJSSHPGFQ-UHFFFAOYSA-N 0.000 description 3
- PYVFQLBTKLTYTG-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-ethyl-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NCC)C(C)(C)C PYVFQLBTKLTYTG-UHFFFAOYSA-N 0.000 description 3
- SVRNPAWUQSRQDR-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-methoxy-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NOC)C(C)(C)C SVRNPAWUQSRQDR-UHFFFAOYSA-N 0.000 description 3
- MERLQASBRDWKDQ-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-methyl-1H-pyrrolo[2,3-b]pyridine-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C1=C(C=2C(=NC(=CC=2)C(=O)NC)N1)Cl)C(C)(C)C MERLQASBRDWKDQ-UHFFFAOYSA-N 0.000 description 3
- QYNGSKKAMMMUSU-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-phenyl-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC1=CC=CC=C1)C(C)(C)C QYNGSKKAMMMUSU-UHFFFAOYSA-N 0.000 description 3
- AHVGUCBWHJIREZ-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-propan-2-yl-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC(C)C)C(C)(C)C AHVGUCBWHJIREZ-UHFFFAOYSA-N 0.000 description 3
- ZKCVPKGPHDGZDJ-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-N,1-dimethylindole-6-carboxamide Chemical compound CNC(=O)c1ccc2cc(-c3nn(c4ncnc(N)c34)C(C)(C)C)n(C)c2c1 ZKCVPKGPHDGZDJ-UHFFFAOYSA-N 0.000 description 3
- VYARLCVNNHTNAM-UHFFFAOYSA-N 2-(4-amino-7-propan-2-ylimidazo[5,1-f][1,2,4]triazin-5-yl)-3-chloro-N-methyl-1H-indole-6-carboxamide Chemical compound NC1=NC=NN2C1=C(N=C2C(C)C)C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC VYARLCVNNHTNAM-UHFFFAOYSA-N 0.000 description 3
- DILHJTZQDCOPRO-UHFFFAOYSA-N 2-(4-amino-7-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-5-yl)-3-chloro-N-methyl-1H-indole-6-carboxamide Chemical compound NC1=NC=NN2C1=C(C=C2C(C)C)C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC DILHJTZQDCOPRO-UHFFFAOYSA-N 0.000 description 3
- VDNPELONOYHGLO-UHFFFAOYSA-N 2-(8-amino-3-propan-2-ylimidazo[1,5-a]pyrazin-1-yl)-N-methyl-1H-indole-6-carboxamide Chemical compound CNC(=O)c1ccc2cc([nH]c2c1)-c1nc(C(C)C)n2ccnc(N)c12 VDNPELONOYHGLO-UHFFFAOYSA-N 0.000 description 3
- CZHZUJVGXKKWOK-UHFFFAOYSA-N 2-[4-amino-1-(1-methylpiperidin-4-yl)pyrazolo[3,4-d]pyrimidin-3-yl]-3-chloro-N-cyclopropyl-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC1CC1)C1CCN(CC1)C CZHZUJVGXKKWOK-UHFFFAOYSA-N 0.000 description 3
- HDRICYBPUIHGFB-UHFFFAOYSA-N 2-[4-amino-1-(1-methylsulfonylpiperidin-4-yl)pyrazolo[3,4-d]pyrimidin-3-yl]-3-chloro-N-methyl-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC)C1CCN(CC1)S(=O)(=O)C HDRICYBPUIHGFB-UHFFFAOYSA-N 0.000 description 3
- ZMQADKSJKPBTEQ-UHFFFAOYSA-N 2-[4-amino-1-(2-aminoethyl)pyrazolo[3,4-d]pyrimidin-3-yl]-3-chloro-N-methyl-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC)CCN ZMQADKSJKPBTEQ-UHFFFAOYSA-N 0.000 description 3
- MTVIBLNIVAZDBD-UHFFFAOYSA-N 2-[4-amino-1-(2-hydroxyethyl)pyrazolo[3,4-d]pyrimidin-3-yl]-3-chloro-N-methyl-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC)CCO MTVIBLNIVAZDBD-UHFFFAOYSA-N 0.000 description 3
- VEEAEHXPQMQIAP-UHFFFAOYSA-N 2-[4-amino-1-(3-methoxypropyl)pyrazolo[3,4-d]pyrimidin-3-yl]-3-chloro-N-methyl-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC)CCCOC VEEAEHXPQMQIAP-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- HOZLFOUMPFCLFK-UHFFFAOYSA-N C(C)(C)N1N=C(C=2C1=NC=NC=2N)C=1NC2=CC(=CC=C2C=1)C=1OC=CN=1 Chemical compound C(C)(C)N1N=C(C=2C1=NC=NC=2N)C=1NC2=CC(=CC=C2C=1)C=1OC=CN=1 HOZLFOUMPFCLFK-UHFFFAOYSA-N 0.000 description 3
- POGSLQNMTATYLA-UHFFFAOYSA-N C(C)(C)N1N=C(C=2C1=NC=NC=2N)C=1NC2=CC(=CC=C2C=1)C=1SC=NN=1 Chemical compound C(C)(C)N1N=C(C=2C1=NC=NC=2N)C=1NC2=CC(=CC=C2C=1)C=1SC=NN=1 POGSLQNMTATYLA-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- NSZXLMVQBNISCL-UHFFFAOYSA-N ClC1=C(NC2=CC(=CC=C12)C=1OC=CN=1)C1=NN(C2=NC=NC(=C21)N)C(C)C Chemical compound ClC1=C(NC2=CC(=CC=C12)C=1OC=CN=1)C1=NN(C2=NC=NC(=C21)N)C(C)C NSZXLMVQBNISCL-UHFFFAOYSA-N 0.000 description 3
- IKMBEAVQWGZKRA-UHFFFAOYSA-N ClC1=C(NC2=CC(=CC=C12)C=1SC=NN=1)C1=NN(C2=NC=NC(=C21)N)C(C)C Chemical compound ClC1=C(NC2=CC(=CC=C12)C=1SC=NN=1)C1=NN(C2=NC=NC(=C21)N)C(C)C IKMBEAVQWGZKRA-UHFFFAOYSA-N 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 102000034615 Glial cell line-derived neurotrophic factor Human genes 0.000 description 3
- 108091010837 Glial cell line-derived neurotrophic factor Proteins 0.000 description 3
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 3
- 239000002118 L01XE12 - Vandetanib Substances 0.000 description 3
- MRYVUVQWSUNDMS-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C1=CC=2C(=NC(=CC=2)C(=O)NC)N1)C(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C1=CC=2C(=NC(=CC=2)C(=O)NC)N1)C(C)(C)C MRYVUVQWSUNDMS-UHFFFAOYSA-N 0.000 description 3
- DWGWMIZXCROVJL-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=C(N=1)C=CC(=C2)C(=O)NC)C(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=C(N=1)C=CC(=C2)C(=O)NC)C(C)(C)C DWGWMIZXCROVJL-UHFFFAOYSA-N 0.000 description 3
- BWGPDIYNLNQCSW-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=C(C=C2C=1)Cl)C(=O)NC)C(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=C(C=C2C=1)Cl)C(=O)NC)C(C)(C)C BWGPDIYNLNQCSW-UHFFFAOYSA-N 0.000 description 3
- CYVKVOPCYGSDOV-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1)C(=O)N)C(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1)C(=O)N)C(C)(C)C CYVKVOPCYGSDOV-UHFFFAOYSA-N 0.000 description 3
- CQRYLFOODJKGGH-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1)C(=O)NC)C1CCCC1 Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1)C(=O)NC)C1CCCC1 CQRYLFOODJKGGH-UHFFFAOYSA-N 0.000 description 3
- CLCBHKJAGRXYEO-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1)C(=O)NC)C1CCCCC1 Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1)C(=O)NC)C1CCCCC1 CLCBHKJAGRXYEO-UHFFFAOYSA-N 0.000 description 3
- IYYBDEQOCKFFNE-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1)C(=O)OC)C(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1)C(=O)OC)C(C)(C)C IYYBDEQOCKFFNE-UHFFFAOYSA-N 0.000 description 3
- BRONVRHOEUHJIF-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1)NC(C)=O)C(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1)NC(C)=O)C(C)(C)C BRONVRHOEUHJIF-UHFFFAOYSA-N 0.000 description 3
- MZFCMOLBCALXEP-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)N(C)C)C(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)N(C)C)C(C)(C)C MZFCMOLBCALXEP-UHFFFAOYSA-N 0.000 description 3
- ZELOUUNVLVPBJP-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC)C ZELOUUNVLVPBJP-UHFFFAOYSA-N 0.000 description 3
- HVKJROZQSCMKQH-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC1=NN(C=C1)CCN1CCN(CC1)C)C(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC1=NN(C=C1)CCN1CCN(CC1)C)C(C)(C)C HVKJROZQSCMKQH-UHFFFAOYSA-N 0.000 description 3
- GIPYCLYLHPZHLE-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NCCCN(C)C)C(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NCCCN(C)C)C(C)(C)C GIPYCLYLHPZHLE-UHFFFAOYSA-N 0.000 description 3
- UTEHJJONBHRFOU-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NCCCN1CCOCC1)C(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NCCCN1CCOCC1)C(C)(C)C UTEHJJONBHRFOU-UHFFFAOYSA-N 0.000 description 3
- BLQNUEVLXIXDHM-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NCCCOC(C)C)C(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NCCCOC(C)C)C(C)(C)C BLQNUEVLXIXDHM-UHFFFAOYSA-N 0.000 description 3
- AZMXUKCEOMXDOI-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NCCCOC)C(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NCCCOC)C(C)(C)C AZMXUKCEOMXDOI-UHFFFAOYSA-N 0.000 description 3
- WOYIZUHDFKAJCV-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NCCN(C)C)C(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NCCN(C)C)C(C)(C)C WOYIZUHDFKAJCV-UHFFFAOYSA-N 0.000 description 3
- GODGGIVMFNQVDU-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NCCOC)C(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NCCOC)C(C)(C)C GODGGIVMFNQVDU-UHFFFAOYSA-N 0.000 description 3
- ZUWBNSACERMTQQ-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NCCOCCN(C)C)C(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NCCOCCN(C)C)C(C)(C)C ZUWBNSACERMTQQ-UHFFFAOYSA-N 0.000 description 3
- KSCPVLNFZOVQNN-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NCCOCCOC)C(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NCCOCCOC)C(C)(C)C KSCPVLNFZOVQNN-UHFFFAOYSA-N 0.000 description 3
- VOEIWTFJUMRPMZ-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(CC)=O)C(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(CC)=O)C(C)(C)C VOEIWTFJUMRPMZ-UHFFFAOYSA-N 0.000 description 3
- CBQZYSQAZNURGI-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1F)C(=O)NC)C(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1F)C(=O)NC)C(C)(C)C CBQZYSQAZNURGI-UHFFFAOYSA-N 0.000 description 3
- ULKCOVLUZIGOCJ-UHFFFAOYSA-N NC1=CC=C2C=C(NC2=C1)C1=NN(C2=NC=NC(=C21)N)C(C)(C)C Chemical compound NC1=CC=C2C=C(NC2=C1)C1=NN(C2=NC=NC(=C21)N)C(C)(C)C ULKCOVLUZIGOCJ-UHFFFAOYSA-N 0.000 description 3
- KNXBHTQVPNVZPO-UHFFFAOYSA-N NC1=NC=C(C2=C1C(=NN2C(C)C)C=1NC2=CC(=CC=C2C=1)C(=O)NC)Cl Chemical compound NC1=NC=C(C2=C1C(=NN2C(C)C)C=1NC2=CC(=CC=C2C=1)C(=O)NC)Cl KNXBHTQVPNVZPO-UHFFFAOYSA-N 0.000 description 3
- CSYZRXAIUWGVQB-UHFFFAOYSA-N NC1=NC=CC2=C1C(=NN2C(C)C)C=1NC2=CC(=CC=C2C=1Br)C(=O)NC Chemical compound NC1=NC=CC2=C1C(=NN2C(C)C)C=1NC2=CC(=CC=C2C=1Br)C(=O)NC CSYZRXAIUWGVQB-UHFFFAOYSA-N 0.000 description 3
- HUZSXLDCKIDHRU-UHFFFAOYSA-N NC1=NC=NN2C1=C(C=C2C(C)C)C=1NC2=CC(=CC=C2C=1)C(=O)NC Chemical compound NC1=NC=NN2C1=C(C=C2C(C)C)C=1NC2=CC(=CC=C2C=1)C(=O)NC HUZSXLDCKIDHRU-UHFFFAOYSA-N 0.000 description 3
- 108091008605 VEGF receptors Proteins 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 3
- 229940034982 antineoplastic agent Drugs 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- OGEBRHQLRGFBNV-RZDIXWSQSA-N chembl2036808 Chemical class C12=NC(NCCCC)=NC=C2C(C=2C=CC(F)=CC=2)=NN1C[C@H]1CC[C@H](N)CC1 OGEBRHQLRGFBNV-RZDIXWSQSA-N 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 125000000842 isoxazolyl group Chemical group 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 3
- 125000002757 morpholinyl group Chemical group 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 125000004193 piperazinyl group Chemical group 0.000 description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 description 3
- 238000001959 radiotherapy Methods 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 3
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 3
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 3
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 3
- 229960000241 vandetanib Drugs 0.000 description 3
- FHNMAOLQZHUPIJ-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-methylpropanoate Chemical compound CC(C)C(=O)ON1C(=O)CCC1=O FHNMAOLQZHUPIJ-UHFFFAOYSA-N 0.000 description 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- NMRKXWXGVJSXML-UHFFFAOYSA-N 1-cyclohexylpyrazolo[3,4-d]pyrimidin-4-amine Chemical compound N1=CC=2C(N)=NC=NC=2N1C1CCCCC1 NMRKXWXGVJSXML-UHFFFAOYSA-N 0.000 description 2
- JBFNKCPQWPOLKI-UHFFFAOYSA-N 1-tert-butyl-3-(2-trimethylsilylethynyl)pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C(C)(C)(C)N1N=C(C=2C1=NC=NC=2N)C#C[Si](C)(C)C JBFNKCPQWPOLKI-UHFFFAOYSA-N 0.000 description 2
- XNZSAEWNGIVBFZ-UHFFFAOYSA-N 1-tert-butyl-3-ethynylpyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C(C)(C)(C)N1N=C(C=2C1=NC=NC=2N)C#C XNZSAEWNGIVBFZ-UHFFFAOYSA-N 0.000 description 2
- SJWBCKIAHBQWER-UHFFFAOYSA-N 3-(4-amino-3-bromopyrazolo[3,4-d]pyrimidin-1-yl)cyclopentan-1-one Chemical compound NC1=C2C(=NC=N1)N(N=C2Br)C1CC(CC1)=O SJWBCKIAHBQWER-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- SOSYGGKAIVNKLX-UHFFFAOYSA-N 3-bromo-1-tert-butylpyrazolo[3,4-d]pyrimidin-4-amine Chemical compound N1=CN=C2N(C(C)(C)C)N=C(Br)C2=C1N SOSYGGKAIVNKLX-UHFFFAOYSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- XXJWYDDUDKYVKI-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(1-pyrrolidinyl)propoxy]quinazoline Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)N=CN=C2C=C1OCCCN1CCCC1 XXJWYDDUDKYVKI-UHFFFAOYSA-N 0.000 description 2
- NUONMXZGVOQRFJ-UHFFFAOYSA-N 4-chloro-3-iodo-1-propan-2-ylpyrazolo[4,3-c]pyridine Chemical compound N1=CC=C2N(C(C)C)N=C(I)C2=C1Cl NUONMXZGVOQRFJ-UHFFFAOYSA-N 0.000 description 2
- PTAATKSPVKTECF-UHFFFAOYSA-N 5-amino-1-cyclohexylpyrazole-4-carbonitrile Chemical compound NC1=C(C#N)C=NN1C1CCCCC1 PTAATKSPVKTECF-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 2
- FJMPLOXEGPAODY-UHFFFAOYSA-N CC(C)C(=O)NCc1n[nH]c(N)nc1=O Chemical compound CC(C)C(=O)NCc1n[nH]c(N)nc1=O FJMPLOXEGPAODY-UHFFFAOYSA-N 0.000 description 2
- GFFKCVRRFNXBGL-UHFFFAOYSA-N CC(C)c1nc(I)c2n1[nH]c(N)nc2=O Chemical compound CC(C)c1nc(I)c2n1[nH]c(N)nc2=O GFFKCVRRFNXBGL-UHFFFAOYSA-N 0.000 description 2
- NPBUKZJDCSZWQL-UHFFFAOYSA-N CC(C)c1nc(I)c2n1[nH]cnc2=O Chemical compound CC(C)c1nc(I)c2n1[nH]cnc2=O NPBUKZJDCSZWQL-UHFFFAOYSA-N 0.000 description 2
- JFZNVRBVFMFUDS-UHFFFAOYSA-N CC(C)c1ncc2n1[nH]c(N)nc2=O Chemical compound CC(C)c1ncc2n1[nH]c(N)nc2=O JFZNVRBVFMFUDS-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- BZKFMUIJRXWWQK-UHFFFAOYSA-N Cyclopentenone Chemical compound O=C1CCC=C1 BZKFMUIJRXWWQK-UHFFFAOYSA-N 0.000 description 2
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 108010009202 Growth Factor Receptors Proteins 0.000 description 2
- 102000009465 Growth Factor Receptors Human genes 0.000 description 2
- 239000007821 HATU Substances 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 102100039064 Interleukin-3 Human genes 0.000 description 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 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 description 2
- FJHHZXWJVIEFGJ-UHFFFAOYSA-N N-(3-methoxy-5-methyl-2-pyrazinyl)-2-[4-(1,3,4-oxadiazol-2-yl)phenyl]-3-pyridinesulfonamide Chemical compound COC1=NC(C)=CN=C1NS(=O)(=O)C1=CC=CN=C1C1=CC=C(C=2OC=NN=2)C=C1 FJHHZXWJVIEFGJ-UHFFFAOYSA-N 0.000 description 2
- OFPFSHBCJYXECJ-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(CC)O)C(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(CC)O)C(C)(C)C OFPFSHBCJYXECJ-UHFFFAOYSA-N 0.000 description 2
- OELFHWCZYCBYCW-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C=O)C(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C=O)C(C)(C)C OELFHWCZYCBYCW-UHFFFAOYSA-N 0.000 description 2
- PBTQUZSMUCGBMM-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)CO)C(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)CO)C(C)(C)C PBTQUZSMUCGBMM-UHFFFAOYSA-N 0.000 description 2
- 101150003085 Pdcl gene Proteins 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 2
- 229920004890 Triton X-100 Polymers 0.000 description 2
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 2
- 239000012391 XPhos Pd G2 Substances 0.000 description 2
- FAHVXNAHFGUFEN-UHFFFAOYSA-N [5-chloro-6-methoxycarbonyl-1-[(2-methylpropan-2-yl)oxycarbonyl]indol-2-yl]boronic acid Chemical compound C(C)(C)(C)OC(=O)N1C(=CC2=CC(=C(C=C12)C(=O)OC)Cl)B(O)O FAHVXNAHFGUFEN-UHFFFAOYSA-N 0.000 description 2
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 238000012382 advanced drug delivery Methods 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 125000004450 alkenylene group Chemical group 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 125000004419 alkynylene group Chemical group 0.000 description 2
- 150000001409 amidines Chemical class 0.000 description 2
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 125000005101 aryl methoxy carbonyl group Chemical group 0.000 description 2
- 125000005002 aryl methyl group Chemical group 0.000 description 2
- 229950010993 atrasentan Drugs 0.000 description 2
- MOTJMGVDPWRKOC-QPVYNBJUSA-N atrasentan Chemical compound C1([C@H]2[C@@H]([C@H](CN2CC(=O)N(CCCC)CCCC)C=2C=C3OCOC3=CC=2)C(O)=O)=CC=C(OC)C=C1 MOTJMGVDPWRKOC-QPVYNBJUSA-N 0.000 description 2
- 125000002393 azetidinyl group Chemical group 0.000 description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 2
- 125000001589 carboacyl group Chemical group 0.000 description 2
- YAYRGNWWLMLWJE-UHFFFAOYSA-L carboplatin Chemical compound O=C1O[Pt](N)(N)OC(=O)C11CCC1 YAYRGNWWLMLWJE-UHFFFAOYSA-L 0.000 description 2
- 229960004562 carboplatin Drugs 0.000 description 2
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 2
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 2
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 2
- 229960004316 cisplatin Drugs 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 2
- 150000004292 cyclic ethers Chemical class 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 229960004397 cyclophosphamide Drugs 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 229960004679 doxorubicin Drugs 0.000 description 2
- 238000009509 drug development Methods 0.000 description 2
- 238000000132 electrospray ionisation Methods 0.000 description 2
- 150000002081 enamines Chemical class 0.000 description 2
- 238000001952 enzyme assay Methods 0.000 description 2
- 229960001433 erlotinib Drugs 0.000 description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
- LIWAQLJGPBVORC-UHFFFAOYSA-N ethylmethylamine Chemical compound CCNC LIWAQLJGPBVORC-UHFFFAOYSA-N 0.000 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 description 2
- 229960005420 etoposide Drugs 0.000 description 2
- 230000000893 fibroproliferative effect Effects 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 229960002584 gefitinib Drugs 0.000 description 2
- 238000001415 gene therapy Methods 0.000 description 2
- 229930004094 glycosylphosphatidylinositol Natural products 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 238000002868 homogeneous time resolved fluorescence Methods 0.000 description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 2
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- PCKPVGOLPKLUHR-UHFFFAOYSA-N indoxyl Chemical group C1=CC=C2C(O)=CNC2=C1 PCKPVGOLPKLUHR-UHFFFAOYSA-N 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 2
- 125000001786 isothiazolyl group Chemical group 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N methanesulfonic acid Substances CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 229960000485 methotrexate Drugs 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 description 2
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 125000003386 piperidinyl group Chemical group 0.000 description 2
- 125000003367 polycyclic group Chemical group 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- VZOPRCCTKLAGPN-ZFJVMAEJSA-L potassium;sodium;(2r,3r)-2,3-dihydroxybutanedioate;tetrahydrate Chemical compound O.O.O.O.[Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O VZOPRCCTKLAGPN-ZFJVMAEJSA-L 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 2
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 2
- 125000002098 pyridazinyl group Chemical group 0.000 description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 2
- SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 2
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 2
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 2
- OUKYUETWWIPKQR-UHFFFAOYSA-N saracatinib Chemical compound C1CN(C)CCN1CCOC1=CC(OC2CCOCC2)=C(C(NC=2C(=CC=C3OCOC3=2)Cl)=NC=N2)C2=C1 OUKYUETWWIPKQR-UHFFFAOYSA-N 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 125000003003 spiro group Chemical group 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 229960004964 temozolomide Drugs 0.000 description 2
- FUHKJIGYKPSRNK-UHFFFAOYSA-N tert-butyl N-(3-bromo-2H-pyrazolo[3,4-d]pyrimidin-4-yl)-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamate Chemical compound BrC1=NNC2=NC=NC(=C21)N(C(OC(C)(C)C)=O)C(=O)OC(C)(C)C FUHKJIGYKPSRNK-UHFFFAOYSA-N 0.000 description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical compound C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 2
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 2
- 229960004528 vincristine Drugs 0.000 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 description 2
- 238000005406 washing Methods 0.000 description 2
- 239000002023 wood Substances 0.000 description 2
- 229950003684 zibotentan Drugs 0.000 description 2
- LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical compound C([C@@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-KRWDZBQOSA-N 0.000 description 1
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- JVCBVWTTXCNJBJ-UHFFFAOYSA-N 1-azabicyclo[2.2.1]heptane Chemical compound C1CC2CCN1C2 JVCBVWTTXCNJBJ-UHFFFAOYSA-N 0.000 description 1
- STHHLVCQSLRQNI-UHFFFAOYSA-N 1-azabicyclo[3.2.1]octane Chemical compound C1C2CCN1CCC2 STHHLVCQSLRQNI-UHFFFAOYSA-N 0.000 description 1
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 description 1
- ABEXEQSGABRUHS-UHFFFAOYSA-N 16-methylheptadecyl 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC(C)C ABEXEQSGABRUHS-UHFFFAOYSA-N 0.000 description 1
- USASUEYARBQNBM-UHFFFAOYSA-N 1h-indol-2-ylboronic acid Chemical class C1=CC=C2NC(B(O)O)=CC2=C1 USASUEYARBQNBM-UHFFFAOYSA-N 0.000 description 1
- OJDWDFYZUCGZAC-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-(1-methylpiperidin-4-yl)-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC1CCN(CC1)C)C(C)(C)C OJDWDFYZUCGZAC-UHFFFAOYSA-N 0.000 description 1
- KFNOKOWQEJSQEE-UHFFFAOYSA-N 2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-N-cyclohexyl-1H-indole-6-carboxamide Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)NC1CCCCC1)C(C)(C)C KFNOKOWQEJSQEE-UHFFFAOYSA-N 0.000 description 1
- HQHCIOGIZVTJAI-UHFFFAOYSA-N 2-(4-amino-3-bromopyrazolo[3,4-d]pyrimidin-1-yl)ethanol Chemical compound NC1=C2C(=NC=N1)N(N=C2Br)CCO HQHCIOGIZVTJAI-UHFFFAOYSA-N 0.000 description 1
- OEICGMPRFOJHKO-UHFFFAOYSA-N 2-(ethoxymethylidene)propanedinitrile Chemical compound CCOC=C(C#N)C#N OEICGMPRFOJHKO-UHFFFAOYSA-N 0.000 description 1
- QPEJAHMNOVMSOZ-UHFFFAOYSA-N 2-azaspiro[3.3]heptane Chemical compound C1CCC21CNC2 QPEJAHMNOVMSOZ-UHFFFAOYSA-N 0.000 description 1
- PHUMXXWPXYBLDE-UHFFFAOYSA-N 2-bromo-1h-indole-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2C=C(Br)NC2=C1 PHUMXXWPXYBLDE-UHFFFAOYSA-N 0.000 description 1
- SHICTOIBUMGLLA-UHFFFAOYSA-N 2-bromo-N-methyl-1H-indole-6-carboxamide Chemical compound BrC=1NC2=CC(=CC=C2C=1)C(=O)NC SHICTOIBUMGLLA-UHFFFAOYSA-N 0.000 description 1
- LDLCZOVUSADOIV-UHFFFAOYSA-N 2-bromoethanol Chemical compound OCCBr LDLCZOVUSADOIV-UHFFFAOYSA-N 0.000 description 1
- ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 1
- DIQOUXNTSMWQSA-UHFFFAOYSA-N 2-oxa-5-azabicyclo[2.2.1]heptane Chemical compound C1OC2CNC1C2 DIQOUXNTSMWQSA-UHFFFAOYSA-N 0.000 description 1
- HPJALMWOZYIZGE-UHFFFAOYSA-N 2-oxa-6-azaspiro[3.3]heptane Chemical compound C1NCC11COC1 HPJALMWOZYIZGE-UHFFFAOYSA-N 0.000 description 1
- ZHAIMJRKJKQNQI-UHFFFAOYSA-N 2-oxa-7-azaspiro[3.4]octane Chemical compound C1OCC11CNCC1 ZHAIMJRKJKQNQI-UHFFFAOYSA-N 0.000 description 1
- RECARUFTCUAFPV-UHFFFAOYSA-N 2-oxa-7-azaspiro[3.5]nonane Chemical compound C1OCC11CCNCC1 RECARUFTCUAFPV-UHFFFAOYSA-N 0.000 description 1
- SDESQEIYRGXXPA-UHFFFAOYSA-N 2-oxa-8-azaspiro[3.5]nonane Chemical compound C1OCC11CNCCC1 SDESQEIYRGXXPA-UHFFFAOYSA-N 0.000 description 1
- 125000004637 2-oxopiperidinyl group Chemical group O=C1N(CCCC1)* 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 1
- IGRCWJPBLWGNPX-UHFFFAOYSA-N 3-(2-chlorophenyl)-n-(4-chlorophenyl)-n,5-dimethyl-1,2-oxazole-4-carboxamide Chemical compound C=1C=C(Cl)C=CC=1N(C)C(=O)C1=C(C)ON=C1C1=CC=CC=C1Cl IGRCWJPBLWGNPX-UHFFFAOYSA-N 0.000 description 1
- CECPPGKTGZZQAG-UHFFFAOYSA-N 3-(4-amino-3-bromopyrazolo[3,4-d]pyrimidin-1-yl)cyclopentan-1-ol Chemical compound NC1=C2C(=NC=N1)N(N=C2Br)C1CC(CC1)O CECPPGKTGZZQAG-UHFFFAOYSA-N 0.000 description 1
- SXJUKKCZXYUJKR-UHFFFAOYSA-N 3-amino-6-(aminomethyl)-2h-1,2,4-triazin-5-one;dihydrochloride Chemical compound Cl.Cl.NCC1=NNC(N)=NC1=O SXJUKKCZXYUJKR-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- RYSCXLWCPNPLPD-UHFFFAOYSA-N 3-bromo-1-cyclohexylpyrazolo[3,4-d]pyrimidin-4-amine Chemical compound BrC1=NN(C2=NC=NC(=C21)N)C1CCCCC1 RYSCXLWCPNPLPD-UHFFFAOYSA-N 0.000 description 1
- URVMLPUJRGPLRA-UHFFFAOYSA-N 3-bromo-1-ethylpyrazolo[3,4-d]pyrimidin-4-amine Chemical compound BrC1=NN(C2=NC=NC(=C21)N)CC URVMLPUJRGPLRA-UHFFFAOYSA-N 0.000 description 1
- DHFYKLULHRGVSL-UHFFFAOYSA-N 3-bromo-1-methylpyrazolo[3,4-d]pyrimidin-4-amine Chemical compound N1=CN=C2N(C)N=C(Br)C2=C1N DHFYKLULHRGVSL-UHFFFAOYSA-N 0.000 description 1
- LXNOMFPYYIOZQW-UHFFFAOYSA-N 3-bromo-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-4-amine Chemical compound N1=CN=C2N(C(C)C)N=C(Br)C2=C1N LXNOMFPYYIOZQW-UHFFFAOYSA-N 0.000 description 1
- OZULUFUHMFFLQF-UHFFFAOYSA-N 3-iodo-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-4-amine Chemical compound N1=CN=C2N(C(C)C)N=C(I)C2=C1N OZULUFUHMFFLQF-UHFFFAOYSA-N 0.000 description 1
- BCKDNSCCRGSIGN-UHFFFAOYSA-N 3-iodo-1-propan-2-ylpyrazolo[4,3-c]pyridin-4-amine Chemical compound N1=CC=C2N(C(C)C)N=C(I)C2=C1N BCKDNSCCRGSIGN-UHFFFAOYSA-N 0.000 description 1
- 238000013030 3-step procedure Methods 0.000 description 1
- 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 description 1
- HHFBDROWDBDFBR-UHFFFAOYSA-N 4-[[9-chloro-7-(2,6-difluorophenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1NC1=NC=C(CN=C(C=2C3=CC=C(Cl)C=2)C=2C(=CC=CC=2F)F)C3=N1 HHFBDROWDBDFBR-UHFFFAOYSA-N 0.000 description 1
- ZOQYGDZCSKQKMG-UHFFFAOYSA-N 4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidine-3-carbaldehyde Chemical compound N1=CN=C2N(C(C)(C)C)N=C(C=O)C2=C1N ZOQYGDZCSKQKMG-UHFFFAOYSA-N 0.000 description 1
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 1
- PBVPGWHQJRFJQU-UHFFFAOYSA-N 4-chloro-3-iodo-2h-pyrazolo[4,3-c]pyridine Chemical compound ClC1=NC=CC2=C1C(I)=NN2 PBVPGWHQJRFJQU-UHFFFAOYSA-N 0.000 description 1
- XCDZWNHCHWCZSW-UHFFFAOYSA-N 4-chloro-3-iodo-6-methyl-1-tritylpyrazolo[4,3-c]pyridine Chemical compound N1=C(I)C=2C(Cl)=NC(C)=CC=2N1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 XCDZWNHCHWCZSW-UHFFFAOYSA-N 0.000 description 1
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
- 239000002677 5-alpha reductase inhibitor Substances 0.000 description 1
- PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 1
- WGHGKAWHSNSROZ-UHFFFAOYSA-N 5-iodo-7-propan-2-ylimidazo[5,1-f][1,2,4]triazin-4-amine Chemical compound CC(C)c1nc(I)c2c(N)ncnn12 WGHGKAWHSNSROZ-UHFFFAOYSA-N 0.000 description 1
- IEUMROSWGBDBFY-UHFFFAOYSA-N 6-amino-5-[2-(4-amino-1-tert-butylpyrazolo[3,4-d]pyrimidin-3-yl)ethynyl]-N-methylpyridine-2-carboxamide Chemical compound NC1=C(C=CC(=N1)C(=O)NC)C#CC1=NN(C2=NC=NC(=C21)N)C(C)(C)C IEUMROSWGBDBFY-UHFFFAOYSA-N 0.000 description 1
- NVTNVIOHHDRIJN-UHFFFAOYSA-N 6-amino-5-bromo-n-methylpyridine-2-carboxamide Chemical compound CNC(=O)C1=CC=C(Br)C(N)=N1 NVTNVIOHHDRIJN-UHFFFAOYSA-N 0.000 description 1
- NVZWMJWMTWOVNJ-UHFFFAOYSA-N 6-azaspiro[3.4]octane Chemical compound C1CCC21CNCC2 NVZWMJWMTWOVNJ-UHFFFAOYSA-N 0.000 description 1
- BDHMQGDCUCSDHX-UHFFFAOYSA-N 6-oxa-2-azaspiro[3.4]octane Chemical compound C1NCC11COCC1 BDHMQGDCUCSDHX-UHFFFAOYSA-N 0.000 description 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- VADZNAWYVBBWNZ-UHFFFAOYSA-N 7-chloro-3-iodo-1-propan-2-ylpyrazolo[4,3-c]pyridin-4-amine Chemical compound ClC=1C2=C(C(=NC=1)N)C(=NN2C(C)C)I VADZNAWYVBBWNZ-UHFFFAOYSA-N 0.000 description 1
- WZFOPYGRZNUWSP-UHFFFAOYSA-N 7-oxa-2-azaspiro[3.5]nonane Chemical compound C1NCC11CCOCC1 WZFOPYGRZNUWSP-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- GBJVVSCPOBPEIT-UHFFFAOYSA-N AZT-1152 Chemical compound N=1C=NC2=CC(OCCCN(CC)CCOP(O)(O)=O)=CC=C2C=1NC(=NN1)C=C1CC(=O)NC1=CC=CC(F)=C1 GBJVVSCPOBPEIT-UHFFFAOYSA-N 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
- 102000012936 Angiostatins Human genes 0.000 description 1
- 108010079709 Angiostatins Proteins 0.000 description 1
- BFYIZQONLCFLEV-DAELLWKTSA-N Aromasine Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(=C)C2=C1 BFYIZQONLCFLEV-DAELLWKTSA-N 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 102000036365 BRCA1 Human genes 0.000 description 1
- 108700020463 BRCA1 Proteins 0.000 description 1
- 101150072950 BRCA1 gene Proteins 0.000 description 1
- 102000052609 BRCA2 Human genes 0.000 description 1
- 108700020462 BRCA2 Proteins 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 208000020084 Bone disease Diseases 0.000 description 1
- 101150008921 Brca2 gene Proteins 0.000 description 1
- 108010037003 Buserelin Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- HVXBOLULGPECHP-WAYWQWQTSA-N Combretastatin A4 Chemical compound C1=C(O)C(OC)=CC=C1\C=C/C1=CC(OC)=C(OC)C(OC)=C1 HVXBOLULGPECHP-WAYWQWQTSA-N 0.000 description 1
- 108010024986 Cyclin-Dependent Kinase 2 Proteins 0.000 description 1
- 108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 description 1
- 102100036239 Cyclin-dependent kinase 2 Human genes 0.000 description 1
- 102100036252 Cyclin-dependent kinase 4 Human genes 0.000 description 1
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
- 102000000311 Cytosine Deaminase Human genes 0.000 description 1
- 108010080611 Cytosine Deaminase Proteins 0.000 description 1
- 108010092160 Dactinomycin Proteins 0.000 description 1
- 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 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- ZQZFYGIXNQKOAV-OCEACIFDSA-N Droloxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=C(O)C=CC=1)\C1=CC=C(OCCN(C)C)C=C1 ZQZFYGIXNQKOAV-OCEACIFDSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 108010041308 Endothelial Growth Factors Proteins 0.000 description 1
- 229940118365 Endothelin receptor antagonist Drugs 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102400001368 Epidermal growth factor Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 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 description 1
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 1
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 201000006850 Familial medullary thyroid carcinoma Diseases 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- VWUXBMIQPBEWFH-WCCTWKNTSA-N Fulvestrant Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3[C@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)CC2=C1 VWUXBMIQPBEWFH-WCCTWKNTSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- BLCLNMBMMGCOAS-URPVMXJPSA-N Goserelin Chemical compound C([C@@H](C(=O)N[C@H](COC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 BLCLNMBMMGCOAS-URPVMXJPSA-N 0.000 description 1
- 108010069236 Goserelin Proteins 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
- 102100024025 Heparanase Human genes 0.000 description 1
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 1
- 102100021866 Hepatocyte growth factor Human genes 0.000 description 1
- 101000904173 Homo sapiens Progonadoliberin-1 Proteins 0.000 description 1
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 1
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 102000014429 Insulin-like growth factor Human genes 0.000 description 1
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 1
- 108010047852 Integrin alphaVbeta3 Proteins 0.000 description 1
- 102000000588 Interleukin-2 Human genes 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 102000004388 Interleukin-4 Human genes 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 241000764238 Isis Species 0.000 description 1
- 208000022120 Jeavons syndrome Diseases 0.000 description 1
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 1
- 239000005411 L01XE02 - Gefitinib Substances 0.000 description 1
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 1
- 239000002147 L01XE04 - Sunitinib Substances 0.000 description 1
- 239000002136 L01XE07 - Lapatinib Substances 0.000 description 1
- XNRVGTHNYCNCFF-UHFFFAOYSA-N Lapatinib ditosylate monohydrate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1.CC1=CC=C(S(O)(=O)=O)C=C1.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 XNRVGTHNYCNCFF-UHFFFAOYSA-N 0.000 description 1
- 108010000817 Leuprolide Proteins 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 229910010082 LiAlH Inorganic materials 0.000 description 1
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 1
- 229940124041 Luteinizing hormone releasing hormone (LHRH) antagonist Drugs 0.000 description 1
- 108700041567 MDR Genes Proteins 0.000 description 1
- 102100028198 Macrophage colony-stimulating factor 1 receptor Human genes 0.000 description 1
- 101710150918 Macrophage colony-stimulating factor 1 receptor Proteins 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 101100340754 Mus musculus Il3 gene Proteins 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- OACHOUGOMAVAFR-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C1=NC2=C(N1)C=C(C=C2)C(=O)OC)C(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C1=NC2=C(N1)C=C(C=C2)C(=O)OC)C(C)(C)C OACHOUGOMAVAFR-UHFFFAOYSA-N 0.000 description 1
- GTFJHFRNRUWZKR-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1)C(=O)O)C(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1)C(=O)O)C(C)(C)C GTFJHFRNRUWZKR-UHFFFAOYSA-N 0.000 description 1
- QFMUALQLKCNRBF-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1)C(=O)OC)C(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1)C(=O)OC)C(C)C QFMUALQLKCNRBF-UHFFFAOYSA-N 0.000 description 1
- VBZJHJKSGBYUJL-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)OC)C(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)OC)C(C)(C)C VBZJHJKSGBYUJL-UHFFFAOYSA-N 0.000 description 1
- RWKDKVVIQUTZOH-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)OC)C(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)OC)C(C)C RWKDKVVIQUTZOH-UHFFFAOYSA-N 0.000 description 1
- QOZAGMRVVQGQDY-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)OC)C1CCN(CC1)C(=O)OC(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(=O)OC)C1CCN(CC1)C(=O)OC(C)(C)C QOZAGMRVVQGQDY-UHFFFAOYSA-N 0.000 description 1
- BZRGKUIZHSWOJO-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC=C(C=C2C=1)C(=O)NC)C(C)(C)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC=C(C=C2C=1)C(=O)NC)C(C)(C)C BZRGKUIZHSWOJO-UHFFFAOYSA-N 0.000 description 1
- 102000004459 Nitroreductase Human genes 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- SCKXCAADGDQQCS-UHFFFAOYSA-N Performic acid Chemical compound OOC=O SCKXCAADGDQQCS-UHFFFAOYSA-N 0.000 description 1
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 1
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 1
- 108030005449 Polo kinases Proteins 0.000 description 1
- 102100024028 Progonadoliberin-1 Human genes 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 108091008611 Protein Kinase B Proteins 0.000 description 1
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 1
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 1
- 229940125905 RET kinase inhibitor Drugs 0.000 description 1
- 108091008551 RET receptors Proteins 0.000 description 1
- 229940127361 Receptor Tyrosine Kinase Inhibitors Drugs 0.000 description 1
- 108060006706 SRC Proteins 0.000 description 1
- 102000001332 SRC Human genes 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 101000996723 Sus scrofa Gonadotropin-releasing hormone receptor Proteins 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- IVTVGDXNLFLDRM-HNNXBMFYSA-N Tomudex Chemical compound C=1C=C2NC(C)=NC(=O)C2=CC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)S1 IVTVGDXNLFLDRM-HNNXBMFYSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 102000004504 Urokinase Plasminogen Activator Receptors Human genes 0.000 description 1
- 108010042352 Urokinase Plasminogen Activator Receptors Proteins 0.000 description 1
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- 229940122803 Vinca alkaloid Drugs 0.000 description 1
- SKDRSUGRICQQCE-UHFFFAOYSA-N [4-chloro-6-methoxycarbonyl-1-[(2-methylpropan-2-yl)oxycarbonyl]indol-2-yl]boronic acid Chemical compound C(C)(C)(C)OC(=O)N1C(=CC2=C(C=C(C=C12)C(=O)OC)Cl)B(O)O SKDRSUGRICQQCE-UHFFFAOYSA-N 0.000 description 1
- CQWVQDQUFCPYQN-UHFFFAOYSA-N [6-[bis[(2-methylpropan-2-yl)oxycarbonyl]amino]-1-[(2-methylpropan-2-yl)oxycarbonyl]indol-2-yl]boronic acid Chemical compound C(C)(C)(C)OC(=O)N(C1=CC=C2C=C(N(C2=C1)C(=O)OC(C)(C)C)B(O)O)C(=O)OC(C)(C)C CQWVQDQUFCPYQN-UHFFFAOYSA-N 0.000 description 1
- IUBLXGVHXZQTTR-UHFFFAOYSA-N [6-methoxycarbonyl-1-(2-trimethylsilylethoxymethyl)indol-2-yl]boronic acid Chemical compound COC(=O)C1=CC=C2C=C(N(C2=C1)COCC[Si](C)(C)C)B(O)O IUBLXGVHXZQTTR-UHFFFAOYSA-N 0.000 description 1
- PYVZXJWQADAHLT-UHFFFAOYSA-N [bromo(difluoro)methyl] diethyl phosphate Chemical compound P(=O)(OC(F)(F)Br)(OCC)OCC PYVZXJWQADAHLT-UHFFFAOYSA-N 0.000 description 1
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 125000005042 acyloxymethyl group Chemical group 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000004849 alkoxymethyl group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 238000010640 amide synthesis reaction Methods 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 229960001220 amsacrine Drugs 0.000 description 1
- XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229960002932 anastrozole Drugs 0.000 description 1
- YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 230000002280 anti-androgenic effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 229940046836 anti-estrogen Drugs 0.000 description 1
- 230000001833 anti-estrogenic effect Effects 0.000 description 1
- 230000003432 anti-folate effect Effects 0.000 description 1
- 230000003302 anti-idiotype Effects 0.000 description 1
- 230000001740 anti-invasion Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 230000002927 anti-mitotic effect Effects 0.000 description 1
- 230000002137 anti-vascular effect Effects 0.000 description 1
- 239000000051 antiandrogen Substances 0.000 description 1
- 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 description 1
- 229940127074 antifolate Drugs 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 239000003080 antimitotic agent Substances 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 239000003886 aromatase inhibitor Substances 0.000 description 1
- 229940046844 aromatase inhibitors Drugs 0.000 description 1
- FZCSTZYAHCUGEM-UHFFFAOYSA-N aspergillomarasmine B Natural products OC(=O)CNC(C(O)=O)CNC(C(O)=O)CC(O)=O FZCSTZYAHCUGEM-UHFFFAOYSA-N 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 239000003719 aurora kinase inhibitor Substances 0.000 description 1
- 229940120638 avastin Drugs 0.000 description 1
- 229960003005 axitinib Drugs 0.000 description 1
- RITAVMQDGBJQJZ-FMIVXFBMSA-N axitinib Chemical compound CNC(=O)C1=CC=CC=C1SC1=CC=C(C(\C=C\C=2N=CC=CC=2)=NN2)C2=C1 RITAVMQDGBJQJZ-FMIVXFBMSA-N 0.000 description 1
- AAMATCKFMHVIDO-UHFFFAOYSA-N azane;1h-pyrrole Chemical compound N.C=1C=CNC=1 AAMATCKFMHVIDO-UHFFFAOYSA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000004602 benzodiazinyl group Chemical group N1=NC(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
- 125000004601 benzofurazanyl group Chemical group N1=C2C(=NO1)C(=CC=C2)* 0.000 description 1
- 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 description 1
- 229960000397 bevacizumab Drugs 0.000 description 1
- 229960000997 bicalutamide Drugs 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- CWBHKBKGKCDGDM-UHFFFAOYSA-N bis[(2,2,2-trifluoroacetyl)oxy]boranyl 2,2,2-trifluoroacetate Chemical compound FC(F)(F)C(=O)OB(OC(=O)C(F)(F)F)OC(=O)C(F)(F)F CWBHKBKGKCDGDM-UHFFFAOYSA-N 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- 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 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 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 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- CUWODFFVMXJOKD-UVLQAERKSA-N buserelin Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 CUWODFFVMXJOKD-UVLQAERKSA-N 0.000 description 1
- 229960002719 buserelin Drugs 0.000 description 1
- 229960002092 busulfan Drugs 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229950002826 canertinib Drugs 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- SKOLWUPSYHWYAM-UHFFFAOYSA-N carbonodithioic O,S-acid Chemical compound SC(S)=O SKOLWUPSYHWYAM-UHFFFAOYSA-N 0.000 description 1
- 229960005243 carmustine Drugs 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 229960002412 cediranib Drugs 0.000 description 1
- 238000012054 celltiter-glo Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 229960005395 cetuximab Drugs 0.000 description 1
- DGLFSNZWRYADFC-UHFFFAOYSA-N chembl2334586 Chemical compound C1CCC2=CN=C(N)N=C2C2=C1NC1=CC=C(C#CC(C)(O)C)C=C12 DGLFSNZWRYADFC-UHFFFAOYSA-N 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 230000035605 chemotaxis Effects 0.000 description 1
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
- 229960004630 chlorambucil Drugs 0.000 description 1
- RSLSVURFMXHEEU-UHFFFAOYSA-M chloropalladium(1+);dicyclohexyl-[3-[2,4,6-tri(propan-2-yl)phenyl]phenyl]phosphane;2-phenylaniline Chemical compound [Pd+]Cl.NC1=CC=CC=C1C1=CC=CC=[C-]1.CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC(P(C2CCCCC2)C2CCCCC2)=C1 RSLSVURFMXHEEU-UHFFFAOYSA-M 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- QZHPTGXQGDFGEN-UHFFFAOYSA-N chromene Chemical compound C1=CC=C2C=C[CH]OC2=C1 QZHPTGXQGDFGEN-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Substances OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 229960005537 combretastatin A-4 Drugs 0.000 description 1
- HVXBOLULGPECHP-UHFFFAOYSA-N combretastatin A4 Natural products C1=C(O)C(OC)=CC=C1C=CC1=CC(OC)=C(OC)C(OC)=C1 HVXBOLULGPECHP-UHFFFAOYSA-N 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 239000007819 coupling partner Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000002875 cyclin dependent kinase inhibitor Substances 0.000 description 1
- 229940043378 cyclin-dependent kinase inhibitor Drugs 0.000 description 1
- 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- JZRHODNPRNTXKO-UHFFFAOYSA-N cyclohexylhydrazine;hydrochloride Chemical compound Cl.NNC1CCCCC1 JZRHODNPRNTXKO-UHFFFAOYSA-N 0.000 description 1
- 125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 description 1
- SNRCKKQHDUIRIY-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloromethane;dichloropalladium;iron(2+) Chemical compound [Fe+2].ClCCl.Cl[Pd]Cl.C1=C[CH-]C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.C1=C[CH-]C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 SNRCKKQHDUIRIY-UHFFFAOYSA-L 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- WLVKDFJTYKELLQ-UHFFFAOYSA-N cyclopropylboronic acid Chemical compound OB(O)C1CC1 WLVKDFJTYKELLQ-UHFFFAOYSA-N 0.000 description 1
- 229960000978 cyproterone acetate Drugs 0.000 description 1
- UWFYSQMTEOIJJG-FDTZYFLXSA-N cyproterone acetate Chemical compound C1=C(Cl)C2=CC(=O)[C@@H]3C[C@@H]3[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 UWFYSQMTEOIJJG-FDTZYFLXSA-N 0.000 description 1
- 229960000684 cytarabine Drugs 0.000 description 1
- 230000002548 cytokinetic effect Effects 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 229960000640 dactinomycin Drugs 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- CFCUWKMKBJTWLW-UHFFFAOYSA-N deoliosyl-3C-alpha-L-digitoxosyl-MTM Natural products CC=1C(O)=C2C(O)=C3C(=O)C(OC4OC(C)C(O)C(OC5OC(C)C(O)C(OC6OC(C)C(O)C(C)(O)C6)C5)C4)C(C(OC)C(=O)C(O)C(C)O)CC3=CC2=CC=1OC(OC(C)C1O)CC1OC1CC(O)C(O)C(C)O1 CFCUWKMKBJTWLW-UHFFFAOYSA-N 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 description 1
- 125000004582 dihydrobenzothienyl group Chemical group S1C(CC2=C1C=CC=C2)* 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- IUNMPGNGSSIWFP-UHFFFAOYSA-N dimethylaminopropylamine Chemical compound CN(C)CCCN IUNMPGNGSSIWFP-UHFFFAOYSA-N 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- 125000005879 dioxolanyl group Chemical group 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
- 230000007783 downstream signaling Effects 0.000 description 1
- 229950004203 droloxifene Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 229940121647 egfr inhibitor Drugs 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000002308 endothelin receptor antagonist Substances 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940095399 enema Drugs 0.000 description 1
- 125000002587 enol group Chemical group 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 229960001904 epirubicin Drugs 0.000 description 1
- 229940082789 erbitux Drugs 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 description 1
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 229960000255 exemestane Drugs 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 description 1
- 229960004039 finasteride Drugs 0.000 description 1
- 238000009093 first-line therapy Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 150000005699 fluoropyrimidines Chemical class 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
- 229960002074 flutamide Drugs 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000004052 folic acid antagonist Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 229960002258 fulvestrant Drugs 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000003838 furazanyl group Chemical group 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
- 238000010363 gene targeting Methods 0.000 description 1
- XLXSAKCOAKORKW-UHFFFAOYSA-N gonadorelin Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 XLXSAKCOAKORKW-UHFFFAOYSA-N 0.000 description 1
- 229960002913 goserelin Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 108010037536 heparanase Proteins 0.000 description 1
- 229940022353 herceptin Drugs 0.000 description 1
- 125000004475 heteroaralkyl group Chemical group 0.000 description 1
- 150000002429 hydrazines Chemical class 0.000 description 1
- 229960001330 hydroxycarbamide Drugs 0.000 description 1
- 229960000908 idarubicin Drugs 0.000 description 1
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
- 229960001101 ifosfamide Drugs 0.000 description 1
- 238000005417 image-selected in vivo spectroscopy Methods 0.000 description 1
- 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 description 1
- 229960002411 imatinib Drugs 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000001024 immunotherapeutic effect Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 150000002485 inorganic esters Chemical group 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 238000012739 integrated shape imaging system Methods 0.000 description 1
- 229940028885 interleukin-4 Drugs 0.000 description 1
- UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 1
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
- FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical group C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 230000008463 key metabolic pathway Effects 0.000 description 1
- 229960004891 lapatinib Drugs 0.000 description 1
- 229960003881 letrozole Drugs 0.000 description 1
- HPJKCIUCZWXJDR-UHFFFAOYSA-N letrozole Chemical compound C1=CC(C#N)=CC=C1C(N1N=CN=C1)C1=CC=C(C#N)C=C1 HPJKCIUCZWXJDR-UHFFFAOYSA-N 0.000 description 1
- GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 1
- 229960004338 leuprorelin Drugs 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000008263 liquid aerosol Substances 0.000 description 1
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 229960002247 lomustine Drugs 0.000 description 1
- DHMTURDWPRKSOA-RUZDIDTESA-N lonafarnib Chemical compound C1CN(C(=O)N)CCC1CC(=O)N1CCC([C@@H]2C3=C(Br)C=C(Cl)C=C3CCC3=CC(Br)=CN=C32)CC1 DHMTURDWPRKSOA-RUZDIDTESA-N 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 1
- 229910001623 magnesium bromide Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000009115 maintenance therapy Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 229950008959 marimastat Drugs 0.000 description 1
- OCSMOTCMPXTDND-OUAUKWLOSA-N marimastat Chemical compound CNC(=O)[C@H](C(C)(C)C)NC(=O)[C@H](CC(C)C)[C@H](O)C(=O)NO OCSMOTCMPXTDND-OUAUKWLOSA-N 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
- 229960004961 mechlorethamine Drugs 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 229960004296 megestrol acetate Drugs 0.000 description 1
- RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 description 1
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
- 229960001924 melphalan Drugs 0.000 description 1
- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000003475 metalloproteinase inhibitor Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- BKYILOFWEAITOU-UHFFFAOYSA-N methyl 1-(2-trimethylsilylethoxymethyl)indole-6-carboxylate Chemical compound COC(=O)C1=CC=C2C=CN(COCC[Si](C)(C)C)C2=C1 BKYILOFWEAITOU-UHFFFAOYSA-N 0.000 description 1
- YXMMAVGJQNAACL-UHFFFAOYSA-N methyl 2-(4-amino-1-piperidin-4-ylpyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-1H-indole-6-carboxylate hydrochloride Chemical compound Cl.COC(=O)c1ccc2c(Cl)c([nH]c2c1)-c1nn(C2CCNCC2)c2ncnc(N)c12 YXMMAVGJQNAACL-UHFFFAOYSA-N 0.000 description 1
- KAOHWSOZICBJOF-UHFFFAOYSA-N methyl 2-(4-amino-2H-pyrazolo[3,4-d]pyrimidin-3-yl)-3-chloro-1-(2-trimethylsilylethoxymethyl)indole-6-carboxylate Chemical compound NC1=C2C(=NC=N1)NN=C2C=1N(C2=CC(=CC=C2C=1Cl)C(=O)OC)COCC[Si](C)(C)C KAOHWSOZICBJOF-UHFFFAOYSA-N 0.000 description 1
- OJTIJVJZLDVMSZ-UHFFFAOYSA-N methyl 2-bromo-1h-indole-6-carboxylate Chemical compound COC(=O)C1=CC=C2C=C(Br)NC2=C1 OJTIJVJZLDVMSZ-UHFFFAOYSA-N 0.000 description 1
- VASPYVJTIYULQT-UHFFFAOYSA-N methyl 2-bromo-3-methyl-1H-indole-6-carboxylate Chemical compound BrC=1NC2=CC(=CC=C2C=1C)C(=O)OC VASPYVJTIYULQT-UHFFFAOYSA-N 0.000 description 1
- IOPLHGOSNCJOOO-UHFFFAOYSA-N methyl 3,4-diaminobenzoate Chemical compound COC(=O)C1=CC=C(N)C(N)=C1 IOPLHGOSNCJOOO-UHFFFAOYSA-N 0.000 description 1
- DYUBOSKPVMRVDM-UHFFFAOYSA-N methyl 3-methyl-1h-indole-6-carboxylate Chemical compound COC(=O)C1=CC=C2C(C)=CNC2=C1 DYUBOSKPVMRVDM-UHFFFAOYSA-N 0.000 description 1
- QSRRZKPKHJHIRB-UHFFFAOYSA-N methyl 4-[(2,5-dichloro-4-methylthiophen-3-yl)sulfonylamino]-2-hydroxybenzoate Chemical compound C1=C(O)C(C(=O)OC)=CC=C1NS(=O)(=O)C1=C(Cl)SC(Cl)=C1C QSRRZKPKHJHIRB-UHFFFAOYSA-N 0.000 description 1
- JUXKOXNZVJDRIQ-UHFFFAOYSA-N methyl 4-chloro-1h-indole-6-carboxylate Chemical compound COC(=O)C1=CC(Cl)=C2C=CNC2=C1 JUXKOXNZVJDRIQ-UHFFFAOYSA-N 0.000 description 1
- OXHPSEFJDMSMRV-UHFFFAOYSA-N methyl 5-chloro-1h-indole-6-carboxylate Chemical compound C1=C(Cl)C(C(=O)OC)=CC2=C1C=CN2 OXHPSEFJDMSMRV-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 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
- 229960004857 mitomycin Drugs 0.000 description 1
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
- PEECTLLHENGOKU-UHFFFAOYSA-N n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC=C1.CN(C)C1=CC=NC=C1 PEECTLLHENGOKU-UHFFFAOYSA-N 0.000 description 1
- LBWFXVZLPYTWQI-IPOVEDGCSA-N n-[2-(diethylamino)ethyl]-5-[(z)-(5-fluoro-2-oxo-1h-indol-3-ylidene)methyl]-2,4-dimethyl-1h-pyrrole-3-carboxamide;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C LBWFXVZLPYTWQI-IPOVEDGCSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 230000014399 negative regulation of angiogenesis Effects 0.000 description 1
- 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 description 1
- 229960002653 nilutamide Drugs 0.000 description 1
- XWXYUMMDTVBTOU-UHFFFAOYSA-N nilutamide Chemical compound O=C1C(C)(C)NC(=O)N1C1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 XWXYUMMDTVBTOU-UHFFFAOYSA-N 0.000 description 1
- 108020001162 nitroreductase Proteins 0.000 description 1
- 125000000018 nitroso group Chemical group N(=O)* 0.000 description 1
- OSTGTTZJOCZWJG-UHFFFAOYSA-N nitrosourea Chemical compound NC(=O)N=NO OSTGTTZJOCZWJG-UHFFFAOYSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000009437 off-target effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 125000000466 oxiranyl group Chemical group 0.000 description 1
- 125000005476 oxopyrrolidinyl group Chemical group 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 229960001972 panitumumab Drugs 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000013610 patient sample Substances 0.000 description 1
- CUIHSIWYWATEQL-UHFFFAOYSA-N pazopanib Chemical compound C1=CC2=C(C)N(C)N=C2C=C1N(C)C(N=1)=CC=NC=1NC1=CC=C(C)C(S(N)(=O)=O)=C1 CUIHSIWYWATEQL-UHFFFAOYSA-N 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 239000002935 phosphatidylinositol 3 kinase inhibitor Substances 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 229960003171 plicamycin Drugs 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 229960000624 procarbazine Drugs 0.000 description 1
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 1
- 239000000583 progesterone congener Substances 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 239000003528 protein farnesyltransferase inhibitor Substances 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 229960004622 raloxifene Drugs 0.000 description 1
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 1
- 229960004432 raltitrexed Drugs 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 229950009919 saracatinib Drugs 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000012363 selectfluor Substances 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- IVDHYUQIDRJSTI-UHFFFAOYSA-N sorafenib tosylate Chemical compound [H+].CC1=CC=C(S([O-])(=O)=O)C=C1.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 IVDHYUQIDRJSTI-UHFFFAOYSA-N 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- VNFWTIYUKDMAOP-UHFFFAOYSA-N sphos Chemical compound COC1=CC=CC(OC)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 VNFWTIYUKDMAOP-UHFFFAOYSA-N 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- 150000003457 sulfones Chemical group 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 description 1
- 229960001796 sunitinib Drugs 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 229940063683 taxotere Drugs 0.000 description 1
- WFWLQNSHRPWKFK-ZCFIWIBFSA-N tegafur Chemical compound O=C1NC(=O)C(F)=CN1[C@@H]1OCCC1 WFWLQNSHRPWKFK-ZCFIWIBFSA-N 0.000 description 1
- 229960001674 tegafur Drugs 0.000 description 1
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
- 229960001278 teniposide Drugs 0.000 description 1
- KYXJIZLQDZNKFT-UHFFFAOYSA-N tert-butyl 4-[4-amino-3-[3-chloro-6-(cyclopropylcarbamoyl)-1H-indol-2-yl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate Chemical compound NC1=C2C(=NC=N1)N(N=C2C=1NC2=CC(=CC=C2C=1Cl)C(NC1CC1)=O)C1CCN(CC1)C(=O)OC(C)(C)C KYXJIZLQDZNKFT-UHFFFAOYSA-N 0.000 description 1
- AXGQOZPVKWDROT-UHFFFAOYSA-N tert-butyl N-(3-bromo-1-cyclopropylpyrazolo[3,4-d]pyrimidin-4-yl)-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamate Chemical compound BrC1=NN(C2=NC=NC(=C21)N(C(OC(C)(C)C)=O)C(=O)OC(C)(C)C)C1CC1 AXGQOZPVKWDROT-UHFFFAOYSA-N 0.000 description 1
- DVDFTRSGEMTSAL-UHFFFAOYSA-N tert-butyl n-(1h-indol-6-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=C2C=CNC2=C1 DVDFTRSGEMTSAL-UHFFFAOYSA-N 0.000 description 1
- IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 1
- 239000012414 tert-butyl nitrite Substances 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- PHCBRBWANGJMHS-UHFFFAOYSA-J tetrasodium;disulfate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O PHCBRBWANGJMHS-UHFFFAOYSA-J 0.000 description 1
- PGAZQSBUJDVGIX-UHFFFAOYSA-N thiazepane Chemical compound C1CCNSCC1 PGAZQSBUJDVGIX-UHFFFAOYSA-N 0.000 description 1
- JWCVYQRPINPYQJ-UHFFFAOYSA-N thiepane Chemical compound C1CCCSCC1 JWCVYQRPINPYQJ-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
- XFCLJVABOIYOMF-QPLCGJKRSA-N toremifene Chemical compound C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 XFCLJVABOIYOMF-QPLCGJKRSA-N 0.000 description 1
- 229960005026 toremifene Drugs 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 229960000575 trastuzumab Drugs 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 229940124676 vascular endothelial growth factor receptor Drugs 0.000 description 1
- 229950000578 vatalanib Drugs 0.000 description 1
- YCOYDOIWSSHVCK-UHFFFAOYSA-N vatalanib Chemical compound C1=CC(Cl)=CC=C1NC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 YCOYDOIWSSHVCK-UHFFFAOYSA-N 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- HHJUWIANJFBDHT-KOTLKJBCSA-N vindesine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(N)=O)N4C)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 HHJUWIANJFBDHT-KOTLKJBCSA-N 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- 229960001771 vorozole Drugs 0.000 description 1
- XLMPPFTZALNBFS-INIZCTEOSA-N vorozole Chemical compound C1([C@@H](C2=CC=C3N=NN(C3=C2)C)N2N=CN=C2)=CC=C(Cl)C=C1 XLMPPFTZALNBFS-INIZCTEOSA-N 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pyridine Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211269931.2A CN115650985B (zh) | 2016-04-15 | 2017-04-18 | 作为ret激酶抑制剂的杂环化合物 |
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB1606631.8 | 2016-04-15 | ||
| GB201606631 | 2016-04-15 | ||
| GB201619277 | 2016-11-14 | ||
| GB1619277.5 | 2016-11-14 | ||
| CN202211269931.2A CN115650985B (zh) | 2016-04-15 | 2017-04-18 | 作为ret激酶抑制剂的杂环化合物 |
| CN201780031509.4A CN109195972B (zh) | 2016-04-15 | 2017-04-18 | 作为ret激酶抑制剂的杂环化合物 |
| PCT/GB2017/051076 WO2017178844A1 (en) | 2016-04-15 | 2017-04-18 | Heterocyclic compounds as ret kinase inhibitors |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201780031509.4A Division CN109195972B (zh) | 2016-04-15 | 2017-04-18 | 作为ret激酶抑制剂的杂环化合物 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115650985A CN115650985A (zh) | 2023-01-31 |
| CN115650985B true CN115650985B (zh) | 2024-08-02 |
Family
ID=58633035
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201780031509.4A Active CN109195972B (zh) | 2016-04-15 | 2017-04-18 | 作为ret激酶抑制剂的杂环化合物 |
| CN202211269931.2A Active CN115650985B (zh) | 2016-04-15 | 2017-04-18 | 作为ret激酶抑制剂的杂环化合物 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201780031509.4A Active CN109195972B (zh) | 2016-04-15 | 2017-04-18 | 作为ret激酶抑制剂的杂环化合物 |
Country Status (24)
| Country | Link |
|---|---|
| US (4) | US10954241B2 (enExample) |
| EP (2) | EP3442980B1 (enExample) |
| JP (3) | JP6943876B2 (enExample) |
| KR (3) | KR20240142568A (enExample) |
| CN (2) | CN109195972B (enExample) |
| AU (3) | AU2017250448C1 (enExample) |
| BR (2) | BR122023026297A2 (enExample) |
| CA (1) | CA3020778A1 (enExample) |
| CY (1) | CY1124478T1 (enExample) |
| DK (1) | DK3442980T3 (enExample) |
| ES (1) | ES2886587T3 (enExample) |
| HR (1) | HRP20211362T1 (enExample) |
| HU (1) | HUE056135T2 (enExample) |
| IL (3) | IL297192A (enExample) |
| LT (1) | LT3442980T (enExample) |
| MX (2) | MX387394B (enExample) |
| PL (1) | PL3442980T3 (enExample) |
| PT (1) | PT3442980T (enExample) |
| RS (1) | RS62322B1 (enExample) |
| RU (1) | RU2742115C2 (enExample) |
| SG (2) | SG10201911665UA (enExample) |
| SI (1) | SI3442980T1 (enExample) |
| SM (1) | SMT202100538T1 (enExample) |
| WO (1) | WO2017178844A1 (enExample) |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2628418T3 (es) | 2010-05-20 | 2017-08-02 | Array Biopharma, Inc. | Compuestos macrocíclicos como inhibidores de la TRK cinasa |
| RS61485B1 (sr) | 2015-07-16 | 2021-03-31 | Array Biopharma Inc | Supstituisana pirazolo [1,5-a] piridinska jedinjenja kao inhibitori ret kinaze |
| IL302209B2 (en) | 2015-11-02 | 2024-06-01 | Blueprint Medicines Corp | Inhibitors of ret |
| LT3442535T (lt) | 2016-04-15 | 2022-10-25 | Cancer Research Technology Limited | Heterocikliniai junginiai kaip ret kinazės inhibitoriai |
| RS62322B1 (sr) * | 2016-04-15 | 2021-10-29 | Cancer Research Tech Ltd | Heterociklična jedinjenja kao inhibitori ret kinaze |
| JOP20190077A1 (ar) | 2016-10-10 | 2019-04-09 | Array Biopharma Inc | مركبات بيرازولو [1، 5-a]بيريدين بها استبدال كمثبطات كيناز ret |
| TWI704148B (zh) | 2016-10-10 | 2020-09-11 | 美商亞雷生物製藥股份有限公司 | 作為ｒｅｔ激酶抑制劑之經取代吡唑并[1,5-a]吡啶化合物 |
| EP3571203B1 (en) | 2017-01-18 | 2023-06-07 | Array BioPharma Inc. | Substituted pyrazolo[1,5-a]pyrazine compounds as ret kinase inhibitors |
| WO2018136663A1 (en) | 2017-01-18 | 2018-07-26 | Array Biopharma, Inc. | Ret inhibitors |
| JOP20190213A1 (ar) | 2017-03-16 | 2019-09-16 | Array Biopharma Inc | مركبات حلقية ضخمة كمثبطات لكيناز ros1 |
| GB201705971D0 (en) | 2017-04-13 | 2017-05-31 | Cancer Res Tech Ltd | Inhibitor compounds |
| TWI791053B (zh) | 2017-10-10 | 2023-02-01 | 美商亞雷生物製藥股份有限公司 | 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之結晶形式及其醫藥組合物 |
| TWI876442B (zh) | 2017-10-10 | 2025-03-11 | 美商絡速藥業公司 | 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之調配物 |
| JOP20180094A1 (ar) | 2017-10-18 | 2019-04-18 | Hk Inno N Corp | مركب حلقي غير متجانس كمثبط بروتين كيناز |
| EP3740491A1 (en) | 2018-01-18 | 2020-11-25 | Array Biopharma, Inc. | Substituted pyrrolo[2,3-d]pyrimidines compounds as ret kinase inhibitors |
| CA3087578C (en) | 2018-01-18 | 2023-08-08 | Array Biopharma Inc. | Substituted pyrazolo[3,4-d]pyrimidine compounds as ret kinase inhibitors |
| CN111615514B (zh) | 2018-01-18 | 2022-10-11 | 奥瑞生物药品公司 | 作为ret激酶抑制剂的取代的吡唑并[4,3-c]吡啶化合物 |
| PT3773589T (pt) | 2018-04-03 | 2024-02-06 | Blueprint Medicines Corp | Inibidor de ret para utilização no tratamento de cancro com alteração de ret |
| EP3774797B1 (en) * | 2018-04-05 | 2025-11-19 | Merck Patent GmbH | Heteroaryl compounds as type ii irak inhibitors and uses hereof |
| JP2022500383A (ja) | 2018-09-10 | 2022-01-04 | アレイ バイオファーマ インコーポレイテッド | Ｒｅｔキナーゼ阻害剤としての縮合複素環式化合物 |
| KR20210125471A (ko) | 2018-10-05 | 2021-10-18 | 안나푸르나 바이오, 인코포레이티드 | Apj 수용체 활성과 관련된 병태를 치료하기 위한 화합물 및 조성물 |
| KR102195348B1 (ko) | 2018-11-15 | 2020-12-24 | 에이치케이이노엔 주식회사 | 단백질 키나제 억제제로서의 신규 화합물 및 이를 포함하는 약제학적 조성물 |
| US12297197B2 (en) * | 2019-04-03 | 2025-05-13 | Guangzhou Baiyunshan Pharmaceutical Holdings Co., Ltd. Baiyunshan Pharmaceutical General Factory | Pyrazolopyridine compound as RET inhibitor and application thereof |
| CN113490670B (zh) * | 2019-08-05 | 2023-06-02 | 北京志健金瑞生物医药科技有限公司 | 含氮多环稠环类化合物,其药物组合物、制备方法和用途 |
| JP7461605B2 (ja) * | 2020-02-20 | 2024-04-04 | 広州白雲山医薬集団股▲フン▼有限公司白雲山制薬総廠 | キノリン系化合物 |
| EP4146654A1 (en) * | 2020-05-07 | 2023-03-15 | Adorx therapeutics Limited | Antagonists of the adenosine a2a receptor |
| CA3183728A1 (en) | 2020-05-29 | 2021-12-02 | Blueprint Medicines Corporation | Solid forms of pralsetinib |
| CN113214294A (zh) * | 2020-06-10 | 2021-08-06 | 深圳铂立健医药有限公司 | 三环化合物、药物组合物及其应用 |
| KR20230104781A (ko) | 2020-10-05 | 2023-07-10 | 인라이븐 테라퓨틱스, 인크. | Bcr-abl 티로신 키나아제의 억제를 위한 5- 및 6-아자인돌 화합물 |
| EP4267559A1 (en) * | 2020-12-22 | 2023-11-01 | Gilead Sciences, Inc. | Substituted indole compounds |
| US20250002471A1 (en) * | 2020-12-22 | 2025-01-02 | Gilead Sciences, Inc. | 6-substituted indole compounds |
| TWI861488B (zh) | 2021-04-16 | 2024-11-11 | 美商基利科學股份有限公司 | 噻吩并吡咯化合物 |
| CN113248518B (zh) * | 2021-06-21 | 2022-03-25 | 山东大学 | 嘧啶哌嗪类衍生物及其制备方法与应用 |
| AU2022341114A1 (en) | 2021-09-10 | 2024-02-29 | Gilead Sciences, Inc. | Thienopyrrole compounds |
| WO2023064843A1 (en) | 2021-10-15 | 2023-04-20 | Stemline Therapeutics, Inc. | Inhibitors of mutant ret kinases for use in treating cancer |
| WO2024151519A2 (en) * | 2023-01-09 | 2024-07-18 | University Of Florida Research Foundatin, Incorporated | Pparg modulators |
| AU2024320585A1 (en) * | 2023-08-09 | 2025-10-02 | Daewoong Pharmaceutical Co., Ltd. | Novel compound, and pharmaceutical composition for prevention or treatment of cancer or tumors comprising same |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101316845A (zh) * | 2005-11-17 | 2008-12-03 | Osi医药有限公司 | 稠合双环mTOR抑制剂 |
| CN102124009A (zh) * | 2008-07-08 | 2011-07-13 | 因特利凯公司 | 激酶抑制剂及其使用方法 |
Family Cites Families (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0322779A3 (en) | 1987-12-29 | 1991-05-08 | Yoshitomi Pharmaceutical Industries, Ltd. | Benzolactam compounds and pharmaceutical uses thereof |
| US5480883A (en) | 1991-05-10 | 1996-01-02 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Bis mono- and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
| CA2369895C (en) * | 1999-01-11 | 2010-12-21 | Princeton University | High affinity inhibitors for target validation and uses thereof |
| US7119200B2 (en) * | 2002-09-04 | 2006-10-10 | Schering Corporation | Pyrazolopyrimidines as cyclin dependent kinase inhibitors |
| US7429596B2 (en) | 2003-06-20 | 2008-09-30 | The Regents Of The University Of California | 1H-pyrrolo [2,3-D] pyrimidine derivatives and methods of use thereof |
| EP1831225A2 (en) | 2004-11-19 | 2007-09-12 | The Regents of the University of California | Anti-inflammatory pyrazolopyrimidines |
| EP1853261B1 (de) | 2005-03-03 | 2017-01-11 | Universität des Saarlandes | Selektive hemmstoffe humaner corticoidsynthasen |
| AR057960A1 (es) | 2005-12-02 | 2007-12-26 | Osi Pharm Inc | Inhibidores de proteina quinasa biciclicos |
| TW201307354A (zh) | 2005-12-29 | 2013-02-16 | Abbott Lab | 蛋白質激酶抑制劑 |
| GB0610242D0 (en) | 2006-05-23 | 2006-07-05 | Novartis Ag | Organic compounds |
| JP2008063278A (ja) | 2006-09-07 | 2008-03-21 | Fujifilm Finechemicals Co Ltd | １−ピリジン−４−イル−インドール類の製造方法 |
| DK2529622T3 (en) | 2006-09-22 | 2018-05-07 | Pharmacyclics Llc | INHIBITORS OF BRUTON-TYROSINKINASE |
| JP2010532756A (ja) * | 2007-07-06 | 2010-10-14 | オーエスアイ・ファーマスーティカルズ・インコーポレーテッド | ｍＴＯＲＣ１及びｍＴＯＲＣ２の両方の阻害剤を含む組み合わせ抗癌療法 |
| WO2009088990A1 (en) | 2008-01-04 | 2009-07-16 | Intellikine, Inc. | Certain chemical entities, compositions and methods |
| US8193182B2 (en) | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
| EP2252293B1 (en) * | 2008-03-14 | 2018-06-27 | Intellikine, LLC | Kinase inhibitors and methods of use |
| US20110224223A1 (en) | 2008-07-08 | 2011-09-15 | The Regents Of The University Of California, A California Corporation | MTOR Modulators and Uses Thereof |
| CA2738429C (en) | 2008-09-26 | 2016-10-25 | Intellikine, Inc. | Heterocyclic kinase inhibitors |
| US20110269779A1 (en) | 2008-11-18 | 2011-11-03 | Intellikine, Inc. | Methods and compositions for treatment of ophthalmic conditions |
| KR101061599B1 (ko) * | 2008-12-05 | 2011-09-02 | 한국과학기술연구원 | 비정상 세포 성장 질환의 치료를 위한 단백질 키나아제 저해제인 신규 인다졸 유도체, 이의 약학적으로 허용가능한염 및 이를 유효성분으로 함유하는 약학적 조성물 |
| PT2496567T (pt) | 2009-11-05 | 2017-11-15 | Rhizen Pharmaceuticals S A | Novos moduladores de quinase benzopiran |
| EP2528919B1 (en) | 2010-01-28 | 2016-11-02 | University of Washington | Compositions and methods for treating toxoplasmosis. cryptosporidiosis and other apicomplexan protozoan related diseases |
| US9765037B2 (en) | 2010-01-28 | 2017-09-19 | University Of Washington Through Its Center For Commercialization | Compositions and methods for treating toxoplasmosis, cryptosporidiosis, and other apicomplexan protozoan related diseases |
| UY33288A (es) * | 2010-03-25 | 2011-10-31 | Glaxosmithkline Llc | Derivados de indolina inhibidores de la proteina quinasa r del reticulo endoplasmatico |
| WO2011153553A2 (en) | 2010-06-04 | 2011-12-08 | The Regents Of The University Of California | Methods and compositions for kinase inhibition |
| WO2012006619A2 (en) | 2010-07-09 | 2012-01-12 | Northeastern University | ANTIPARASITIC AGENTS BASED ON mTOR INHIBITORS |
| TWI592411B (zh) | 2011-02-23 | 2017-07-21 | 英特爾立秦有限責任公司 | 激酶抑制劑之組合及其用途 |
| US20140357651A1 (en) | 2011-05-04 | 2014-12-04 | Yi Liu | Combination pharmaceutical compositions and uses thereof |
| HK1198579A1 (en) | 2011-08-10 | 2015-04-30 | Novartis Pharma Ag | Jak p13k/mtor combination therapy |
| WO2013077921A2 (en) * | 2011-09-02 | 2013-05-30 | The Regents Of The University Of California | Substituted pyrazolo[3,4-d]pyrimidines and uses thereof |
| EP2776441A4 (en) | 2011-11-08 | 2015-04-08 | Intellikine Llc | TREATMENT METHOD WITH MULTIPLE PHARMACEUTICAL AGENTS |
| US20130209543A1 (en) | 2011-11-23 | 2013-08-15 | Intellikine Llc | Enhanced treatment regimens using mtor inhibitors |
| US8501724B1 (en) | 2012-01-31 | 2013-08-06 | Pharmacyclics, Inc. | Purinone compounds as kinase inhibitors |
| US8889730B2 (en) | 2012-04-10 | 2014-11-18 | Pfizer Inc. | Indole and indazole compounds that activate AMPK |
| US9738610B2 (en) | 2012-09-24 | 2017-08-22 | Whitehead Institute For Biomedical Research | Indazole derivatives and uses thereof |
| GB201217285D0 (en) | 2012-09-27 | 2012-11-14 | Univ Central Lancashire | Indole derivatives |
| WO2014151147A1 (en) | 2013-03-15 | 2014-09-25 | Intellikine, Llc | Combination of kinase inhibitors and uses thereof |
| US9724354B2 (en) | 2013-03-22 | 2017-08-08 | Millennium Pharmaceuticals, Inc. | Combination of catalytic mTORC1/2 inhibitors and selective inhibitors of Aurora A kinase |
| EP3057970A1 (en) | 2013-10-18 | 2016-08-24 | Medivation Technologies, Inc. | Heterocyclic compounds and methods of use |
| US20160272645A1 (en) | 2013-10-18 | 2016-09-22 | Medivation Technologies, Inc. | Heterocyclic Compounds and Methods of Use |
| GB201321146D0 (en) * | 2013-11-29 | 2014-01-15 | Cancer Rec Tech Ltd | Quinazoline compounds |
| EA039885B1 (ru) * | 2014-11-14 | 2022-03-23 | НЕРВИАНО МЕДИКАЛ САЙЕНСИЗ С.р.л. | Производные 6-амино-7-бицикло-7-деазапурина в качестве ингибиторов протеинкиназы |
| AU2016211630B2 (en) | 2015-01-26 | 2021-03-25 | University Of Washington | Compositions and methods for treating toxoplasmosis, cryptosporidiosis and other apicomplexan protozoan related diseases |
| EP3334430B1 (en) | 2015-08-13 | 2025-02-26 | San Diego State University Research Foundation | Atropisomerism for increased kinase inhibitor selectivity |
| KR20180109842A (ko) * | 2015-09-16 | 2018-10-08 | 록쏘 온콜로지, 인코포레이티드 | 화합물 |
| WO2017160717A2 (en) | 2016-03-15 | 2017-09-21 | Memorial Sloan Kettering Cancer Center | Method of treating diseases using kinase modulators |
| LT3442535T (lt) | 2016-04-15 | 2022-10-25 | Cancer Research Technology Limited | Heterocikliniai junginiai kaip ret kinazės inhibitoriai |
| RS62322B1 (sr) | 2016-04-15 | 2021-10-29 | Cancer Research Tech Ltd | Heterociklična jedinjenja kao inhibitori ret kinaze |
-
2017
- 2017-04-18 RS RS20211115A patent/RS62322B1/sr unknown
- 2017-04-18 US US16/093,854 patent/US10954241B2/en active Active
- 2017-04-18 SM SM20210538T patent/SMT202100538T1/it unknown
- 2017-04-18 EP EP17719687.0A patent/EP3442980B1/en active Active
- 2017-04-18 PL PL17719687T patent/PL3442980T3/pl unknown
- 2017-04-18 IL IL297192A patent/IL297192A/en unknown
- 2017-04-18 BR BR122023026297-2A patent/BR122023026297A2/pt not_active Application Discontinuation
- 2017-04-18 LT LTEPPCT/GB2017/051076T patent/LT3442980T/lt unknown
- 2017-04-18 CN CN201780031509.4A patent/CN109195972B/zh active Active
- 2017-04-18 SG SG10201911665UA patent/SG10201911665UA/en unknown
- 2017-04-18 HR HRP20211362TT patent/HRP20211362T1/hr unknown
- 2017-04-18 SI SI201730892T patent/SI3442980T1/sl unknown
- 2017-04-18 EP EP21172597.3A patent/EP3960180A1/en active Pending
- 2017-04-18 KR KR1020247030356A patent/KR20240142568A/ko not_active Withdrawn
- 2017-04-18 WO PCT/GB2017/051076 patent/WO2017178844A1/en not_active Ceased
- 2017-04-18 KR KR1020187032842A patent/KR102390578B1/ko active Active
- 2017-04-18 HU HUE17719687A patent/HUE056135T2/hu unknown
- 2017-04-18 PT PT177196870T patent/PT3442980T/pt unknown
- 2017-04-18 JP JP2018554114A patent/JP6943876B2/ja active Active
- 2017-04-18 BR BR112018071097-0A patent/BR112018071097B1/pt active IP Right Grant
- 2017-04-18 CA CA3020778A patent/CA3020778A1/en active Pending
- 2017-04-18 IL IL289793A patent/IL289793B2/en unknown
- 2017-04-18 RU RU2018138471A patent/RU2742115C2/ru active
- 2017-04-18 MX MX2018012609A patent/MX387394B/es unknown
- 2017-04-18 CN CN202211269931.2A patent/CN115650985B/zh active Active
- 2017-04-18 DK DK17719687.0T patent/DK3442980T3/da active
- 2017-04-18 SG SG11201808878UA patent/SG11201808878UA/en unknown
- 2017-04-18 ES ES17719687T patent/ES2886587T3/es active Active
- 2017-04-18 AU AU2017250448A patent/AU2017250448C1/en active Active
- 2017-04-18 KR KR1020227013172A patent/KR102706837B1/ko active Active
-
2018
- 2018-10-07 IL IL262185A patent/IL262185B/en unknown
- 2018-10-15 MX MX2021013110A patent/MX2021013110A/es unknown
-
2020
- 2020-08-18 AU AU2020220079A patent/AU2020220079B2/en active Active
-
2021
- 2021-02-02 US US17/165,151 patent/US11548896B2/en active Active
- 2021-09-06 CY CY20211100784T patent/CY1124478T1/el unknown
- 2021-09-07 JP JP2021145468A patent/JP2021193108A/ja active Pending
-
2022
- 2022-06-06 AU AU2022203916A patent/AU2022203916A1/en not_active Abandoned
- 2022-11-22 US US17/992,049 patent/US20230339954A1/en not_active Abandoned
-
2023
- 2023-08-10 JP JP2023131211A patent/JP2023159230A/ja active Pending
-
2024
- 2024-12-03 US US18/967,321 patent/US20250236624A1/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101316845A (zh) * | 2005-11-17 | 2008-12-03 | Osi医药有限公司 | 稠合双环mTOR抑制剂 |
| CN102124009A (zh) * | 2008-07-08 | 2011-07-13 | 因特利凯公司 | 激酶抑制剂及其使用方法 |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN115650985B (zh) | 作为ret激酶抑制剂的杂环化合物 | |
| US11661423B2 (en) | Heterocyclic compounds as RET kinase inhibitors | |
| CN115785100B (zh) | 适用作ret抑制剂的化合物 | |
| HK40071396A (en) | Heterocyclic compounds as ret kinase inhibitors | |
| HK40085278A (en) | Heterocyclic compounds as ret kinase inhibitors | |
| HK1260208B (en) | Heterocyclic compounds as ret kinase inhibitors | |
| HK1260373A1 (en) | Heterocyclic compounds as ret kinase inhibitors | |
| HK1260373B (en) | Heterocyclic compounds as ret kinase inhibitors | |
| NZ787350A (en) | Heterocyclic compounds as ret kinase inhibitors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |