JP7311720B2 - Il4i1阻害剤及び使用方法 - Google Patents
Il4i1阻害剤及び使用方法 Download PDFInfo
- Publication number
- JP7311720B2 JP7311720B2 JP2022567075A JP2022567075A JP7311720B2 JP 7311720 B2 JP7311720 B2 JP 7311720B2 JP 2022567075 A JP2022567075 A JP 2022567075A JP 2022567075 A JP2022567075 A JP 2022567075A JP 7311720 B2 JP7311720 B2 JP 7311720B2
- Authority
- JP
- Japan
- Prior art keywords
- mmol
- methyl
- benzo
- dihydro
- added
- 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
- 238000000034 method Methods 0.000 title description 77
- 229940122630 IL4I1 inhibitor Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 252
- 239000003814 drug Substances 0.000 claims description 76
- 206010028980 Neoplasm Diseases 0.000 claims description 73
- 150000003839 salts Chemical class 0.000 claims description 64
- 201000011510 cancer Diseases 0.000 claims description 61
- 125000003118 aryl group Chemical group 0.000 claims description 48
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 39
- 229910052736 halogen Inorganic materials 0.000 claims description 37
- 150000002367 halogens Chemical class 0.000 claims description 37
- 239000000460 chlorine Chemical group 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 239000001257 hydrogen Substances 0.000 claims description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 15
- 229910052801 chlorine Inorganic materials 0.000 claims description 15
- 239000011737 fluorine Substances 0.000 claims description 15
- 229910052731 fluorine Inorganic materials 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- 125000005466 alkylenyl group Chemical group 0.000 claims description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
- 239000003937 drug carrier Substances 0.000 claims description 12
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 10
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
- 150000002431 hydrogen Chemical class 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 363
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 163
- 230000002829 reductive effect Effects 0.000 description 151
- 239000000203 mixture Substances 0.000 description 147
- 239000011541 reaction mixture Substances 0.000 description 141
- -1 cycloheteroalkyl Chemical group 0.000 description 140
- 235000019439 ethyl acetate Nutrition 0.000 description 131
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 119
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 114
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 106
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 99
- 238000003756 stirring Methods 0.000 description 85
- 238000005481 NMR spectroscopy Methods 0.000 description 75
- 238000006243 chemical reaction Methods 0.000 description 74
- 238000002360 preparation method Methods 0.000 description 74
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 64
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 58
- 229940079593 drug Drugs 0.000 description 57
- 239000003480 eluent Substances 0.000 description 56
- 238000010898 silica gel chromatography Methods 0.000 description 52
- 108010008292 L-Amino Acid Oxidase Proteins 0.000 description 51
- 102100026388 L-amino-acid oxidase Human genes 0.000 description 51
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 49
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 47
- 239000012044 organic layer Substances 0.000 description 46
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 46
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 45
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 45
- 239000003208 petroleum Substances 0.000 description 44
- 239000000463 material Substances 0.000 description 43
- 239000012267 brine Substances 0.000 description 42
- 125000000753 cycloalkyl group Chemical group 0.000 description 42
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 42
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 40
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 39
- 125000001072 heteroaryl group Chemical group 0.000 description 39
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
- 239000000243 solution Substances 0.000 description 36
- 239000007832 Na2SO4 Substances 0.000 description 35
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 35
- 239000000706 filtrate Substances 0.000 description 35
- 238000004128 high performance liquid chromatography Methods 0.000 description 35
- 229910052938 sodium sulfate Inorganic materials 0.000 description 35
- 235000011152 sodium sulphate Nutrition 0.000 description 35
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 32
- 229910052757 nitrogen Inorganic materials 0.000 description 31
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 30
- 239000003607 modifier Substances 0.000 description 30
- 125000003545 alkoxy group Chemical group 0.000 description 28
- 239000011734 sodium Substances 0.000 description 28
- 102100040678 Programmed cell death protein 1 Human genes 0.000 description 25
- 241000282414 Homo sapiens Species 0.000 description 24
- 210000004027 cell Anatomy 0.000 description 24
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 22
- 235000019341 magnesium sulphate Nutrition 0.000 description 22
- 125000001424 substituent group Chemical group 0.000 description 22
- 101710089372 Programmed cell death protein 1 Proteins 0.000 description 21
- 229960002621 pembrolizumab Drugs 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- 229940124060 PD-1 antagonist Drugs 0.000 description 20
- 239000000543 intermediate Substances 0.000 description 19
- 239000007787 solid Substances 0.000 description 19
- 208000013056 classic Hodgkin lymphoma Diseases 0.000 description 18
- 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 18
- 229950009791 durvalumab Drugs 0.000 description 18
- 239000000047 product Substances 0.000 description 18
- 229950002916 avelumab Drugs 0.000 description 17
- 230000015572 biosynthetic process Effects 0.000 description 17
- 239000007858 starting material Substances 0.000 description 17
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 16
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 15
- 229960003301 nivolumab Drugs 0.000 description 15
- 238000000746 purification Methods 0.000 description 15
- 238000003786 synthesis reaction Methods 0.000 description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 14
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 14
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 description 14
- 229960003852 atezolizumab Drugs 0.000 description 14
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 description 14
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 14
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 13
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 13
- 206010036711 Primary mediastinal large B-cell lymphomas Diseases 0.000 description 13
- 239000003795 chemical substances by application Substances 0.000 description 13
- 239000013058 crude material Substances 0.000 description 13
- 238000010511 deprotection reaction Methods 0.000 description 13
- 229910000104 sodium hydride Inorganic materials 0.000 description 13
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 description 12
- 125000000217 alkyl group Chemical group 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 238000011282 treatment Methods 0.000 description 12
- 150000001412 amines Chemical class 0.000 description 11
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 11
- 239000012074 organic phase Substances 0.000 description 11
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 11
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- 101001117317 Homo sapiens Programmed cell death 1 ligand 1 Proteins 0.000 description 10
- 101000611936 Homo sapiens Programmed cell death protein 1 Proteins 0.000 description 10
- 206010025323 Lymphomas Diseases 0.000 description 10
- 239000002253 acid Substances 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- GMUWCTKADZFKLT-UHFFFAOYSA-N tert-butyl 2-oxo-3h-benzimidazole-1-carboxylate Chemical compound C1=CC=C2NC(=O)N(C(=O)OC(C)(C)C)C2=C1 GMUWCTKADZFKLT-UHFFFAOYSA-N 0.000 description 10
- 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 10
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 9
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 238000005859 coupling reaction Methods 0.000 description 9
- 201000010099 disease Diseases 0.000 description 9
- 125000001188 haloalkyl group Chemical group 0.000 description 9
- 125000002950 monocyclic group Chemical group 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 9
- 238000002560 therapeutic procedure Methods 0.000 description 9
- TXNLQUKVUJITMX-UHFFFAOYSA-N 4-tert-butyl-2-(4-tert-butylpyridin-2-yl)pyridine Chemical compound CC(C)(C)C1=CC=NC(C=2N=CC=C(C=2)C(C)(C)C)=C1 TXNLQUKVUJITMX-UHFFFAOYSA-N 0.000 description 8
- 108010074708 B7-H1 Antigen Proteins 0.000 description 8
- SHGAZHPCJJPHSC-NUEINMDLSA-N Isotretinoin Chemical compound OC(=O)C=C(C)/C=C/C=C(C)C=CC1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-NUEINMDLSA-N 0.000 description 8
- 206010027406 Mesothelioma Diseases 0.000 description 8
- 206010061535 Ovarian neoplasm Diseases 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 230000008878 coupling Effects 0.000 description 8
- 238000010168 coupling process Methods 0.000 description 8
- 239000012467 final product Substances 0.000 description 8
- 125000004438 haloalkoxy group Chemical group 0.000 description 8
- UUVWYPNAQBNQJQ-UHFFFAOYSA-N hexamethylmelamine Chemical compound CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 description 8
- 239000000377 silicon dioxide Substances 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- 206010008342 Cervix carcinoma Diseases 0.000 description 7
- 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 7
- 208000017604 Hodgkin disease Diseases 0.000 description 7
- 101100407308 Mus musculus Pdcd1lg2 gene Proteins 0.000 description 7
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
- 108700030875 Programmed Cell Death 1 Ligand 2 Proteins 0.000 description 7
- 208000005718 Stomach Neoplasms Diseases 0.000 description 7
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 7
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 7
- 230000001668 ameliorated effect Effects 0.000 description 7
- 239000005557 antagonist Substances 0.000 description 7
- 150000001499 aryl bromides Chemical class 0.000 description 7
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 7
- 229910000024 caesium carbonate Inorganic materials 0.000 description 7
- 201000010881 cervical cancer Diseases 0.000 description 7
- 239000012043 crude product Substances 0.000 description 7
- 206010017758 gastric cancer Diseases 0.000 description 7
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 7
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 7
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 7
- 230000001394 metastastic effect Effects 0.000 description 7
- 206010061289 metastatic neoplasm Diseases 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- 201000011549 stomach cancer Diseases 0.000 description 7
- 238000004808 supercritical fluid chromatography Methods 0.000 description 7
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 7
- 229910052725 zinc Inorganic materials 0.000 description 7
- 239000011701 zinc Substances 0.000 description 7
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 6
- 206010006187 Breast cancer Diseases 0.000 description 6
- 208000026310 Breast neoplasm Diseases 0.000 description 6
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 6
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 6
- 208000032818 Microsatellite Instability Diseases 0.000 description 6
- 206010033128 Ovarian cancer Diseases 0.000 description 6
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000013543 active substance Substances 0.000 description 6
- 229960000473 altretamine Drugs 0.000 description 6
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 6
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 6
- 102000048776 human CD274 Human genes 0.000 description 6
- 102000048362 human PDCD1 Human genes 0.000 description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 230000002265 prevention Effects 0.000 description 6
- 230000000306 recurrent effect Effects 0.000 description 6
- 229910052717 sulfur Inorganic materials 0.000 description 6
- 229940124597 therapeutic agent Drugs 0.000 description 6
- 206010044412 transitional cell carcinoma Diseases 0.000 description 6
- 125000005919 1,2,2-trimethylpropyl group Chemical group 0.000 description 5
- 125000005918 1,2-dimethylbutyl group Chemical group 0.000 description 5
- PKYCWFICOKSIHZ-UHFFFAOYSA-N 1-(3,7-dihydroxyphenoxazin-10-yl)ethanone Chemical compound OC1=CC=C2N(C(=O)C)C3=CC=C(O)C=C3OC2=C1 PKYCWFICOKSIHZ-UHFFFAOYSA-N 0.000 description 5
- 125000006218 1-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 5
- PWKNBLFSJAVFAB-UHFFFAOYSA-N 1-fluoro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1F PWKNBLFSJAVFAB-UHFFFAOYSA-N 0.000 description 5
- QUUKNKHOBYXVBQ-UHFFFAOYSA-N 2-[(4-bromophenyl)methyl]-1,3,4-oxadiazole Chemical compound Brc1ccc(Cc2nnco2)cc1 QUUKNKHOBYXVBQ-UHFFFAOYSA-N 0.000 description 5
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 5
- 125000005916 2-methylpentyl group Chemical group 0.000 description 5
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- 125000005917 3-methylpentyl group Chemical group 0.000 description 5
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 description 5
- 206010009944 Colon cancer Diseases 0.000 description 5
- 208000008839 Kidney Neoplasms Diseases 0.000 description 5
- 206010027480 Metastatic malignant melanoma Diseases 0.000 description 5
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 5
- 208000019569 Nodular lymphocyte predominant Hodgkin lymphoma Diseases 0.000 description 5
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
- 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 5
- 230000029936 alkylation Effects 0.000 description 5
- 238000005804 alkylation reaction Methods 0.000 description 5
- 229910052786 argon Inorganic materials 0.000 description 5
- 125000002619 bicyclic group Chemical group 0.000 description 5
- 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 5
- OCMNCWNTDDVHFK-UHFFFAOYSA-L dichloronickel;1,2-dimethoxyethane Chemical compound Cl[Ni]Cl.COCCOC OCMNCWNTDDVHFK-UHFFFAOYSA-L 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 5
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 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 5
- 208000021039 metastatic melanoma Diseases 0.000 description 5
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 5
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 5
- 125000003386 piperidinyl group Chemical group 0.000 description 5
- 125000004076 pyridyl group Chemical group 0.000 description 5
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- XRNVSPDQTPVECU-UHFFFAOYSA-N (4-bromophenyl)methanamine Chemical compound NCC1=CC=C(Br)C=C1 XRNVSPDQTPVECU-UHFFFAOYSA-N 0.000 description 4
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 4
- MPOYBFYHRQBZPM-UHFFFAOYSA-N 3h-pyridin-4-one Chemical class O=C1CC=NC=C1 MPOYBFYHRQBZPM-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- 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 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- UPIQDFTZQXEVAM-UHFFFAOYSA-N CC(C)(C)OC(N(C(C=CC=C1)=C1N1CC2=CC=C(CBr)C=C2)C1=O)=O Chemical compound CC(C)(C)OC(N(C(C=CC=C1)=C1N1CC2=CC=C(CBr)C=C2)C1=O)=O UPIQDFTZQXEVAM-UHFFFAOYSA-N 0.000 description 4
- ATPDYWFULNVUFO-UHFFFAOYSA-N CC(NCC1=CC=C(CN(C(C=CC=C2)=C2N2)C2=O)C=C1)=O Chemical compound CC(NCC1=CC=C(CN(C(C=CC=C2)=C2N2)C2=O)C=C1)=O ATPDYWFULNVUFO-UHFFFAOYSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- 201000009030 Carcinoma Diseases 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
- 239000007821 HATU Substances 0.000 description 4
- 101001117312 Homo sapiens Programmed cell death 1 ligand 2 Proteins 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 4
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- 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 4
- POAXJXNQKHOWMW-UHFFFAOYSA-N O=C1N(C(F)F)C2=CC=CC=C2N1 Chemical compound O=C1N(C(F)F)C2=CC=CC=C2N1 POAXJXNQKHOWMW-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 206010038389 Renal cancer Diseases 0.000 description 4
- 206010039491 Sarcoma Diseases 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- 210000001744 T-lymphocyte Anatomy 0.000 description 4
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 4
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 4
- 208000024770 Thyroid neoplasm Diseases 0.000 description 4
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 4
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 4
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 description 4
- 125000004935 benzoxazolinyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 4
- 125000001070 dihydroindolyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 4
- 125000000532 dioxanyl group Chemical group 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 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 4
- 238000009472 formulation Methods 0.000 description 4
- 125000002632 imidazolidinyl group Chemical group 0.000 description 4
- 239000011630 iodine Substances 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 4
- 201000010982 kidney cancer Diseases 0.000 description 4
- 230000014759 maintenance of location Effects 0.000 description 4
- 201000001441 melanoma Diseases 0.000 description 4
- 125000002757 morpholinyl group Chemical group 0.000 description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 125000004193 piperazinyl group Chemical group 0.000 description 4
- 125000003367 polycyclic group Chemical group 0.000 description 4
- 235000011181 potassium carbonates Nutrition 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 239000011593 sulfur Substances 0.000 description 4
- NUANLVJLUYWSER-UHFFFAOYSA-N tert-butyl n-[[4-(aminomethyl)phenyl]methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1=CC=C(CN)C=C1 NUANLVJLUYWSER-UHFFFAOYSA-N 0.000 description 4
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 4
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 4
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 4
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 4
- 201000002510 thyroid cancer Diseases 0.000 description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 4
- 208000023747 urothelial carcinoma Diseases 0.000 description 4
- HQIAQKKFLSHREB-UHFFFAOYSA-N 1,4-bis(bromomethyl)-2-iodobenzene Chemical compound BrCC1=CC=C(CBr)C(I)=C1 HQIAQKKFLSHREB-UHFFFAOYSA-N 0.000 description 3
- XGCKXFIEBXHNRH-UHFFFAOYSA-N 2-(2-oxo-3h-benzimidazol-1-yl)acetic acid Chemical compound C1=CC=C2NC(=O)N(CC(=O)O)C2=C1 XGCKXFIEBXHNRH-UHFFFAOYSA-N 0.000 description 3
- CAVXKYRRHDMKIP-UHFFFAOYSA-N 2-(4-bromophenyl)acetohydrazide Chemical compound NNC(=O)CC1=CC=C(Br)C=C1 CAVXKYRRHDMKIP-UHFFFAOYSA-N 0.000 description 3
- AYPSHJCKSDNETA-UHFFFAOYSA-N 2-chloro-1h-benzimidazole Chemical compound C1=CC=C2NC(Cl)=NC2=C1 AYPSHJCKSDNETA-UHFFFAOYSA-N 0.000 description 3
- YQHJFPFNGVDEDT-UHFFFAOYSA-N 2-tert-butyl-1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(N(C)C)=NC(C)(C)C YQHJFPFNGVDEDT-UHFFFAOYSA-N 0.000 description 3
- XAUDJQYHKZQPEU-KVQBGUIXSA-N 5-aza-2'-deoxycytidine Chemical compound O=C1N=C(N)N=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 XAUDJQYHKZQPEU-KVQBGUIXSA-N 0.000 description 3
- DZRTZDURJKZGSP-UHFFFAOYSA-N 5-fluoro-1,3-dihydrobenzimidazol-2-one Chemical compound FC1=CC=C2NC(=O)NC2=C1 DZRTZDURJKZGSP-UHFFFAOYSA-N 0.000 description 3
- 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 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- 208000003950 B-cell lymphoma Diseases 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 3
- TWNUZJWYPBEPCT-UHFFFAOYSA-N CC(C)(C)OC(N(C(C=CC=C1)=C1N1CC(O)=O)C1=O)=O Chemical compound CC(C)(C)OC(N(C(C=CC=C1)=C1N1CC(O)=O)C1=O)=O TWNUZJWYPBEPCT-UHFFFAOYSA-N 0.000 description 3
- ITXWMHABEFGNFX-UHFFFAOYSA-N CC(C)(C)OC(N(C(C=CC=C1)=C1N1CC2=CC(I)=CC=C2)C1=O)=O Chemical compound CC(C)(C)OC(N(C(C=CC=C1)=C1N1CC2=CC(I)=CC=C2)C1=O)=O ITXWMHABEFGNFX-UHFFFAOYSA-N 0.000 description 3
- BBQCLEVSFYXHDF-UHFFFAOYSA-N CC(NCC1=CC(OC)=C(CN(C(C=CC=C2)=C2N2)C2=O)C=C1)=O Chemical compound CC(NCC1=CC(OC)=C(CN(C(C=CC=C2)=C2N2)C2=O)C=C1)=O BBQCLEVSFYXHDF-UHFFFAOYSA-N 0.000 description 3
- IEWRIJMPSWLSJL-UHFFFAOYSA-N CN(CC1)CCN1C1=CC=CC(CN(C(C=CC=C2)=C2N2)C2=O)=C1 Chemical compound CN(CC1)CCN1C1=CC=CC(CN(C(C=CC=C2)=C2N2)C2=O)=C1 IEWRIJMPSWLSJL-UHFFFAOYSA-N 0.000 description 3
- GPZPVAGAVUVVRB-UHFFFAOYSA-N CNC(C1C2=CC=C(CN(C(C=CC=C3)=C3N3)C3=O)C=C2CC1)=O Chemical compound CNC(C1C2=CC=C(CN(C(C=CC=C3)=C3N3)C3=O)C=C2CC1)=O GPZPVAGAVUVVRB-UHFFFAOYSA-N 0.000 description 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 3
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 3
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 3
- 108010092160 Dactinomycin Proteins 0.000 description 3
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 3
- 230000005526 G1 to G0 transition Effects 0.000 description 3
- 208000021309 Germ cell tumor Diseases 0.000 description 3
- 208000032320 Germ cell tumor of testis Diseases 0.000 description 3
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 3
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 3
- 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 3
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 3
- NCBVDHUBBIYXPR-UHFFFAOYSA-N N#CC1(CC(N=CC(CN(C2=CC=CC=C2N2)C2=O)=C2)=C2Cl)CCC1 Chemical compound N#CC1(CC(N=CC(CN(C2=CC=CC=C2N2)C2=O)=C2)=C2Cl)CCC1 NCBVDHUBBIYXPR-UHFFFAOYSA-N 0.000 description 3
- CFOSJCLGZOHIBW-UHFFFAOYSA-N N-[(2-methoxyphenyl)methyl]-2-methyl-6-nitroaniline Chemical compound COC1=CC=CC=C1CNC1=C(C)C=CC=C1[N+]([O-])=O CFOSJCLGZOHIBW-UHFFFAOYSA-N 0.000 description 3
- 208000034176 Neoplasms, Germ Cell and Embryonal Diseases 0.000 description 3
- ZJXNSGXLGRVWEW-UHFFFAOYSA-N O=C1N(CC(C=C2)=CC=C2Br)CCC1(F)F Chemical compound O=C1N(CC(C=C2)=CC=C2Br)CCC1(F)F ZJXNSGXLGRVWEW-UHFFFAOYSA-N 0.000 description 3
- DHKNPQYPBRRKMR-UHFFFAOYSA-N O=C1N(CC(C=CC(CBr)=C2)=C2I)CCC1 Chemical compound O=C1N(CC(C=CC(CBr)=C2)=C2I)CCC1 DHKNPQYPBRRKMR-UHFFFAOYSA-N 0.000 description 3
- JVKYTGJVXNFHDO-UHFFFAOYSA-N O=C1N(CC2=CC=C(CC3=NN=CO3)C(Cl)=C2)C(C=CC=C2)=C2N1 Chemical compound O=C1N(CC2=CC=C(CC3=NN=CO3)C(Cl)=C2)C(C=CC=C2)=C2N1 JVKYTGJVXNFHDO-UHFFFAOYSA-N 0.000 description 3
- COGPZCFGTRGUKB-UHFFFAOYSA-N OC(C1=CC(CN(C(C=CC=C2)=C2N2)C2=O)=CC=C1)=O Chemical compound OC(C1=CC(CN(C(C=CC=C2)=C2N2)C2=O)=CC=C1)=O COGPZCFGTRGUKB-UHFFFAOYSA-N 0.000 description 3
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 3
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 3
- 239000012346 acetyl chloride Substances 0.000 description 3
- 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 3
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 238000005576 amination reaction Methods 0.000 description 3
- 239000000908 ammonium hydroxide Substances 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 3
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 3
- 201000000053 blastoma Diseases 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 208000029742 colonic neoplasm Diseases 0.000 description 3
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 3
- 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 3
- 201000008184 embryoma Diseases 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 201000004101 esophageal cancer Diseases 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- 102000037865 fusion proteins Human genes 0.000 description 3
- 108020001507 fusion proteins Proteins 0.000 description 3
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 3
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 3
- 230000000155 isotopic effect Effects 0.000 description 3
- BTNMPGBKDVTSJY-UHFFFAOYSA-N keto-phenylpyruvic acid Chemical compound OC(=O)C(=O)CC1=CC=CC=C1 BTNMPGBKDVTSJY-UHFFFAOYSA-N 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 239000002502 liposome Substances 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- DASQOOZCTWOQPA-GXKRWWSZSA-L methotrexate disodium Chemical compound [Na+].[Na+].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 DASQOOZCTWOQPA-GXKRWWSZSA-L 0.000 description 3
- LBCOZLABSCFRLI-UHFFFAOYSA-N methyl 4-[(2-oxo-3h-benzimidazol-1-yl)methyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CN1C(=O)NC2=CC=CC=C21 LBCOZLABSCFRLI-UHFFFAOYSA-N 0.000 description 3
- NQAASRWRCHYEBM-UHFFFAOYSA-N methyl n-(2-bromophenyl)carbamate Chemical compound COC(=O)NC1=CC=CC=C1Br NQAASRWRCHYEBM-UHFFFAOYSA-N 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 229910000160 potassium phosphate Inorganic materials 0.000 description 3
- 235000011009 potassium phosphates Nutrition 0.000 description 3
- 238000004007 reversed phase HPLC Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 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 3
- GLLNJLGDDWIBQG-UHFFFAOYSA-N tert-butyl 5-fluoro-2-oxo-3H-benzimidazole-1-carboxylate Chemical compound FC1=CC2=C(N(C(N2)=O)C(=O)OC(C)(C)C)C=C1 GLLNJLGDDWIBQG-UHFFFAOYSA-N 0.000 description 3
- 208000002918 testicular germ cell tumor Diseases 0.000 description 3
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 3
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 3
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 3
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 2
- DLUFGSSNIBZCNZ-UHFFFAOYSA-N (3-chlorothiophen-2-yl)methanamine Chemical compound NCC=1SC=CC=1Cl DLUFGSSNIBZCNZ-UHFFFAOYSA-N 0.000 description 2
- CAAOMIYPIICAKB-UHFFFAOYSA-N (3-chlorothiophen-2-yl)methanol Chemical compound OCC=1SC=CC=1Cl CAAOMIYPIICAKB-UHFFFAOYSA-N 0.000 description 2
- QJIMTLTYXBDJFC-UHFFFAOYSA-N (4-methylphenyl)-diphenylphosphane Chemical compound C1=CC(C)=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QJIMTLTYXBDJFC-UHFFFAOYSA-N 0.000 description 2
- KXDXFEJOOBZAMB-UHFFFAOYSA-N (5-bromo-3-methylthiophen-2-yl)methanamine Chemical compound CC=1C=C(Br)SC=1CN KXDXFEJOOBZAMB-UHFFFAOYSA-N 0.000 description 2
- SILNNFMWIMZVEQ-UHFFFAOYSA-N 1,3-dihydrobenzimidazol-2-one Chemical compound C1=CC=C2NC(O)=NC2=C1 SILNNFMWIMZVEQ-UHFFFAOYSA-N 0.000 description 2
- RBZMSGOBSOCYHR-UHFFFAOYSA-N 1,4-bis(bromomethyl)benzene Chemical compound BrCC1=CC=C(CBr)C=C1 RBZMSGOBSOCYHR-UHFFFAOYSA-N 0.000 description 2
- MRRZTMRYKHWRSO-UHFFFAOYSA-N 1-(3-fluoro-2-nitrophenyl)pyrrolidine Chemical compound [O-][N+](=O)C1=C(F)C=CC=C1N1CCCC1 MRRZTMRYKHWRSO-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
- SWHWZPYRONFNMO-UHFFFAOYSA-N 1-[(4-bromophenyl)methyl]-2H-pyrrol-5-one Chemical compound Brc1ccc(CN2CC=CC2=O)cc1 SWHWZPYRONFNMO-UHFFFAOYSA-N 0.000 description 2
- XHILZRONKPMVRX-UHFFFAOYSA-N 1-[(4-bromophenyl)methyl]pyrrolidin-2-one Chemical compound C1=CC(Br)=CC=C1CN1C(=O)CCC1 XHILZRONKPMVRX-UHFFFAOYSA-N 0.000 description 2
- GKVXOWMXYRQAIP-UHFFFAOYSA-N 1-benzylthieno[3,2-d][1,3]oxazine-2,4-dione Chemical compound O=C1OC(=O)C=2SC=CC=2N1CC1=CC=CC=C1 GKVXOWMXYRQAIP-UHFFFAOYSA-N 0.000 description 2
- YLRBJYMANQKEAW-UHFFFAOYSA-N 1-bromo-4-(bromomethyl)benzene Chemical compound BrCC1=CC=C(Br)C=C1 YLRBJYMANQKEAW-UHFFFAOYSA-N 0.000 description 2
- QHTTXSWWWSYDRY-UHFFFAOYSA-N 1h-thieno[3,2-d][1,3]oxazine-2,4-dione Chemical compound O=C1OC(=O)NC2=C1SC=C2 QHTTXSWWWSYDRY-UHFFFAOYSA-N 0.000 description 2
- 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 description 2
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 2
- PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 2
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 2
- BRGWBLVOBBLKET-UHFFFAOYSA-N 3-(1-phenylethyl)-1h-benzimidazol-2-one Chemical compound C12=CC=CC=C2NC(=O)N1C(C)C1=CC=CC=C1 BRGWBLVOBBLKET-UHFFFAOYSA-N 0.000 description 2
- WUNDUQNDDMRLQP-UHFFFAOYSA-N 3-(piperidin-4-ylmethyl)-1H-benzimidazol-2-one Chemical compound O=C1NC2=CC=CC=C2N1CC1CCNCC1 WUNDUQNDDMRLQP-UHFFFAOYSA-N 0.000 description 2
- OKYFECACYVXJAW-UHFFFAOYSA-N 3-(pyridin-3-ylmethyl)-1h-benzimidazol-2-one Chemical compound O=C1NC2=CC=CC=C2N1CC1=CC=CN=C1 OKYFECACYVXJAW-UHFFFAOYSA-N 0.000 description 2
- DQYJENDUHFMGEK-UHFFFAOYSA-N 3-[(4-bromophenyl)methyl]-4-methyl-1,2,4-triazole Chemical compound CN1C=NN=C1CC1=CC=C(Br)C=C1 DQYJENDUHFMGEK-UHFFFAOYSA-N 0.000 description 2
- NJXPYZHXZZCTNI-UHFFFAOYSA-N 3-aminobenzonitrile Chemical compound NC1=CC=CC(C#N)=C1 NJXPYZHXZZCTNI-UHFFFAOYSA-N 0.000 description 2
- CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 2
- PUKKVMZZENXNSR-UHFFFAOYSA-N 3-chlorothiophene-2-carboxamide Chemical compound NC(=O)C=1SC=CC=1Cl PUKKVMZZENXNSR-UHFFFAOYSA-N 0.000 description 2
- BXEAAHIHFFIMIE-UHFFFAOYSA-N 3-chlorothiophene-2-carboxylic acid Chemical compound OC(=O)C=1SC=CC=1Cl BXEAAHIHFFIMIE-UHFFFAOYSA-N 0.000 description 2
- MNYFCKIQWAXRBS-UHFFFAOYSA-N 3-quinolin-8-yloxypropan-1-amine Chemical compound C1=CN=C2C(OCCCN)=CC=CC2=C1 MNYFCKIQWAXRBS-UHFFFAOYSA-N 0.000 description 2
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 2
- DYPQFBIOJFWFBD-UHFFFAOYSA-N 4-[(2-oxo-3h-benzimidazol-1-yl)methyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1CN1C(=O)NC2=CC=CC=C21 DYPQFBIOJFWFBD-UHFFFAOYSA-N 0.000 description 2
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
- NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 description 2
- SKOAVMCNVURZCZ-UHFFFAOYSA-N 5-bromo-2-(bromomethyl)-3-chlorothiophene Chemical compound BrC1=CC(=C(S1)CBr)Cl SKOAVMCNVURZCZ-UHFFFAOYSA-N 0.000 description 2
- RMYIZBJGFRCIHF-UHFFFAOYSA-N 5-bromo-3-chlorothiophene-2-carboxamide Chemical compound C1=C(SC(=C1Cl)C(=O)N)Br RMYIZBJGFRCIHF-UHFFFAOYSA-N 0.000 description 2
- PODJNSZMZSXMOL-UHFFFAOYSA-N 5-bromo-n-methylthiophene-3-carboxamide Chemical compound CNC(=O)C1=CSC(Br)=C1 PODJNSZMZSXMOL-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- 241001251200 Agelas Species 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- 206010061424 Anal cancer Diseases 0.000 description 2
- 208000007860 Anus Neoplasms Diseases 0.000 description 2
- 241001530392 Aphos Species 0.000 description 2
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
- 206010005003 Bladder cancer Diseases 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- KCTKLSZFCYEBDH-UHFFFAOYSA-N CC(C)(C)OC(CC1=CC(CN(C(C=CC=C2)=C2N2)C2=O)=CC=C1)=O Chemical compound CC(C)(C)OC(CC1=CC(CN(C(C=CC=C2)=C2N2)C2=O)=CC=C1)=O KCTKLSZFCYEBDH-UHFFFAOYSA-N 0.000 description 2
- ACDWDMZOBAWDRP-UHFFFAOYSA-N CC(C)(C)OC(CC1=CC=C(CN(C(C=C(C=C2)F)=C2N2)C2=O)C=C1)=O Chemical compound CC(C)(C)OC(CC1=CC=C(CN(C(C=C(C=C2)F)=C2N2)C2=O)C=C1)=O ACDWDMZOBAWDRP-UHFFFAOYSA-N 0.000 description 2
- DKPGOBCEKYBFLN-UHFFFAOYSA-N CC(C)(C)OC(N(C(C1=C2)=CC=C2Br)N=C1C#N)=O Chemical compound CC(C)(C)OC(N(C(C1=C2)=CC=C2Br)N=C1C#N)=O DKPGOBCEKYBFLN-UHFFFAOYSA-N 0.000 description 2
- IZHLKRKQHPEBKA-UHFFFAOYSA-N CC(C)(C)OC(N(C(C=CC(C)=C1)=C1N1CC2=CC=CC=C2OC)C1=O)=O Chemical compound CC(C)(C)OC(N(C(C=CC(C)=C1)=C1N1CC2=CC=CC=C2OC)C1=O)=O IZHLKRKQHPEBKA-UHFFFAOYSA-N 0.000 description 2
- SISJRPITQINTSM-UHFFFAOYSA-N CC(C)(C)OC(N(C(C=CC=C1)=C1N1CC(C2)C2C2=NC=C(C)C=C2)C1=O)=O Chemical compound CC(C)(C)OC(N(C(C=CC=C1)=C1N1CC(C2)C2C2=NC=C(C)C=C2)C1=O)=O SISJRPITQINTSM-UHFFFAOYSA-N 0.000 description 2
- ZJTKFAPNSPKSEQ-UHFFFAOYSA-N CC(C)(C)OC(N(C(C=CC=C1)=C1N1CC2=CC(C(NC)=O)=CS2)C1=O)=O Chemical compound CC(C)(C)OC(N(C(C=CC=C1)=C1N1CC2=CC(C(NC)=O)=CS2)C1=O)=O ZJTKFAPNSPKSEQ-UHFFFAOYSA-N 0.000 description 2
- HDZYRRXXJZQERX-UHFFFAOYSA-N CC(C)(C)OC(N(C(C=CC=C1)=C1N1CC2=CC=C(CN(C)C(C)=O)C=C2)C1=O)=O Chemical compound CC(C)(C)OC(N(C(C=CC=C1)=C1N1CC2=CC=C(CN(C)C(C)=O)C=C2)C1=O)=O HDZYRRXXJZQERX-UHFFFAOYSA-N 0.000 description 2
- MWDXKRLGAGXITI-UHFFFAOYSA-N CC(C)(C)OC(N(C(C=CC=C1)=C1N1CC2=CC=C(CN(CCC3)C3=O)C=C2)C1=O)=O Chemical compound CC(C)(C)OC(N(C(C=CC=C1)=C1N1CC2=CC=C(CN(CCC3)C3=O)C=C2)C1=O)=O MWDXKRLGAGXITI-UHFFFAOYSA-N 0.000 description 2
- KLDFXEGPBBDZFQ-UHFFFAOYSA-N CC(C)(C)OC(N(C(C=CC=C1)=C1N1CC2=CC=C(CN=[N+]=[N-])C=C2)C1=O)=O Chemical compound CC(C)(C)OC(N(C(C=CC=C1)=C1N1CC2=CC=C(CN=[N+]=[N-])C=C2)C1=O)=O KLDFXEGPBBDZFQ-UHFFFAOYSA-N 0.000 description 2
- VCNOOBQSDLJRRE-UHFFFAOYSA-N CC(C)(C)OC(N(C(C=CC=C1)=C1N1CC2=CC=C(CNS(C)(=O)=O)C=C2)C1=O)=O Chemical compound CC(C)(C)OC(N(C(C=CC=C1)=C1N1CC2=CC=C(CNS(C)(=O)=O)C=C2)C1=O)=O VCNOOBQSDLJRRE-UHFFFAOYSA-N 0.000 description 2
- NFJUWINHLPLUIF-UHFFFAOYSA-N CC(C)(C)OC(N(C(C=CC=C1)=C1N1CCCI)C1=O)=O Chemical compound CC(C)(C)OC(N(C(C=CC=C1)=C1N1CCCI)C1=O)=O NFJUWINHLPLUIF-UHFFFAOYSA-N 0.000 description 2
- YUERRUXQNARJMY-UHFFFAOYSA-M CC(C)(C)OC(N(C(C=CC=C1)=C1N1CCC[P+](C2=CC=CC=C2)(C2=CC=CC=C2)C2=CC=CC=C2)C1=O)=O.[I-] Chemical compound CC(C)(C)OC(N(C(C=CC=C1)=C1N1CCC[P+](C2=CC=CC=C2)(C2=CC=CC=C2)C2=CC=CC=C2)C1=O)=O.[I-] YUERRUXQNARJMY-UHFFFAOYSA-M 0.000 description 2
- LMHNZXCMIZNKNA-UHFFFAOYSA-N CC(C)(C)OC(N1C2=CC=C(CN(C(C=CC=C3)=C3N3)C3=O)C=C2CC1)=O Chemical compound CC(C)(C)OC(N1C2=CC=C(CN(C(C=CC=C3)=C3N3)C3=O)C=C2CC1)=O LMHNZXCMIZNKNA-UHFFFAOYSA-N 0.000 description 2
- HUPIBBLRCXLGKY-UHFFFAOYSA-N CC(C)(C)OC(NCC1=CC=C(CC2=NN=CO2)C=C1)=O Chemical compound CC(C)(C)OC(NCC1=CC=C(CC2=NN=CO2)C=C1)=O HUPIBBLRCXLGKY-UHFFFAOYSA-N 0.000 description 2
- GDZGSETXYMCPKW-UHFFFAOYSA-N CC(C)(C)OC(NCC1=CC=C(CN(C(C=C(C)C=C2)=C2N2)C2=O)C=C1)=O Chemical compound CC(C)(C)OC(NCC1=CC=C(CN(C(C=C(C)C=C2)=C2N2)C2=O)C=C1)=O GDZGSETXYMCPKW-UHFFFAOYSA-N 0.000 description 2
- ZXSICQXZNUOHRI-UHFFFAOYSA-N CC(C)(C)OC(NCC1=CC=C(CN(C(C=C(C=C2)Cl)=C2N2)C2=O)C=C1)=O Chemical compound CC(C)(C)OC(NCC1=CC=C(CN(C(C=C(C=C2)Cl)=C2N2)C2=O)C=C1)=O ZXSICQXZNUOHRI-UHFFFAOYSA-N 0.000 description 2
- RFSZLKYPKRHTJV-UHFFFAOYSA-N CC(C)(C)OC(NCC1=CC=C(CN(C(C=CC=C2)=C2N2C(F)F)C2=O)C=C1)=O Chemical compound CC(C)(C)OC(NCC1=CC=C(CN(C(C=CC=C2)=C2N2C(F)F)C2=O)C=C1)=O RFSZLKYPKRHTJV-UHFFFAOYSA-N 0.000 description 2
- AVTSWTAUDNPHKJ-UHFFFAOYSA-N CC(C)(C)OC(NCC1=CC=C(CNC(C=C(C=C2)F)=C2[N+]([O-])=O)C=C1)=O Chemical compound CC(C)(C)OC(NCC1=CC=C(CNC(C=C(C=C2)F)=C2[N+]([O-])=O)C=C1)=O AVTSWTAUDNPHKJ-UHFFFAOYSA-N 0.000 description 2
- AEXHBTGUIPNZNE-UHFFFAOYSA-N CC(C)(C)OC(NCC1=CC=C(CNC(C=CC=C2)=C2[N+]([O-])=O)C=C1)=O Chemical compound CC(C)(C)OC(NCC1=CC=C(CNC(C=CC=C2)=C2[N+]([O-])=O)C=C1)=O AEXHBTGUIPNZNE-UHFFFAOYSA-N 0.000 description 2
- NMPJORPZXIJSGA-UHFFFAOYSA-N CC(C)(C)OC(NCCCOC1=C2N=CC=CC2=CC=C1)=O Chemical compound CC(C)(C)OC(NCCCOC1=C2N=CC=CC2=CC=C1)=O NMPJORPZXIJSGA-UHFFFAOYSA-N 0.000 description 2
- VPUDEGPVONEJSV-UHFFFAOYSA-N CC(C1CCCCC1)N(C(C=CC=C1)=C1N1)C1=O Chemical compound CC(C1CCCCC1)N(C(C=CC=C1)=C1N1)C1=O VPUDEGPVONEJSV-UHFFFAOYSA-N 0.000 description 2
- SUHDAXLHVLEWBN-UHFFFAOYSA-N CC(C=C1)=CC(N2CC3=CC=C(CN)C=C3)=C1NC2=O Chemical compound CC(C=C1)=CC(N2CC3=CC=C(CN)C=C3)=C1NC2=O SUHDAXLHVLEWBN-UHFFFAOYSA-N 0.000 description 2
- OJACYRYGDYGRHF-UHFFFAOYSA-N CC(N(C)CC1=CC=C(CBr)C=C1)=O Chemical compound CC(N(C)CC1=CC=C(CBr)C=C1)=O OJACYRYGDYGRHF-UHFFFAOYSA-N 0.000 description 2
- WBHRXXZHNOSHNY-UHFFFAOYSA-N CC(N(C)CC1=CC=C(CN(C(C=CC=C2)=C2N2)C2=O)C=C1)=O Chemical compound CC(N(C)CC1=CC=C(CN(C(C=CC=C2)=C2N2)C2=O)C=C1)=O WBHRXXZHNOSHNY-UHFFFAOYSA-N 0.000 description 2
- VIHGSNOGYNSZTQ-UHFFFAOYSA-N CC(NC1C2=CC(CN(C(C=CC=C3)=C3N3)C3=O)=CC=C2CC1)=O Chemical compound CC(NC1C2=CC(CN(C(C=CC=C3)=C3N3)C3=O)=CC=C2CC1)=O VIHGSNOGYNSZTQ-UHFFFAOYSA-N 0.000 description 2
- JWIPAXVBHIOSOR-UHFFFAOYSA-N CC(NCC(C=CC(CN(C(C=CC=C1)=C1N1)C1=O)=C1)=C1Cl)=O Chemical compound CC(NCC(C=CC(CN(C(C=CC=C1)=C1N1)C1=O)=C1)=C1Cl)=O JWIPAXVBHIOSOR-UHFFFAOYSA-N 0.000 description 2
- QAICHUGIFDYYEI-UHFFFAOYSA-N CC(NCC1=CC=C(CN(C(C=CC=C2)=C2N2C(F)F)C2=O)C=C1)=O Chemical compound CC(NCC1=CC=C(CN(C(C=CC=C2)=C2N2C(F)F)C2=O)C=C1)=O QAICHUGIFDYYEI-UHFFFAOYSA-N 0.000 description 2
- VWSNQLVZXPNQKO-FPYGCLRLSA-N CC1=C(/C=N/O)SC(Br)=C1 Chemical compound CC1=C(/C=N/O)SC(Br)=C1 VWSNQLVZXPNQKO-FPYGCLRLSA-N 0.000 description 2
- LUDRLJVIMOFWLS-UHFFFAOYSA-N CC1=C(CC2=NN=CO2)C=CC(Br)=C1 Chemical compound CC1=C(CC2=NN=CO2)C=CC(Br)=C1 LUDRLJVIMOFWLS-UHFFFAOYSA-N 0.000 description 2
- KXZYAOIAYHZIJG-UHFFFAOYSA-N CC1=C(CC2=NN=CO2)C=CC(CN(C(C=CC=C2)=C2N2)C2=O)=C1 Chemical compound CC1=C(CC2=NN=CO2)C=CC(CN(C(C=CC=C2)=C2N2)C2=O)=C1 KXZYAOIAYHZIJG-UHFFFAOYSA-N 0.000 description 2
- BHBMZCFIFSAZKI-UHFFFAOYSA-N CC1=CN=C(C2C(CN(C(C=CC=C3)=C3N3)C3=O)C2)C=C1 Chemical compound CC1=CN=C(C2C(CN(C(C=CC=C3)=C3N3)C3=O)C2)C=C1 BHBMZCFIFSAZKI-UHFFFAOYSA-N 0.000 description 2
- JICVDZCVCPORLT-UHFFFAOYSA-N CCC(C=C1)=CC(N2)=C1N(CC1=CC=CC=C1)C2=O Chemical compound CCC(C=C1)=CC(N2)=C1N(CC1=CC=CC=C1)C2=O JICVDZCVCPORLT-UHFFFAOYSA-N 0.000 description 2
- ZBNLYOVJQMSQMJ-UHFFFAOYSA-N CCCS(NCC1=CC=C(CN(C(C=C(C=C2)F)=C2N2)C2=O)C=C1)(=O)=O Chemical compound CCCS(NCC1=CC=C(CN(C(C=C(C=C2)F)=C2N2)C2=O)C=C1)(=O)=O ZBNLYOVJQMSQMJ-UHFFFAOYSA-N 0.000 description 2
- GCXZPVZRARVUJA-UHFFFAOYSA-N CCOC(CC1=CC=C(CNC(C=CC=C2)=C2N)C=C1)=O Chemical compound CCOC(CC1=CC=C(CNC(C=CC=C2)=C2N)C=C1)=O GCXZPVZRARVUJA-UHFFFAOYSA-N 0.000 description 2
- ULGAWHNZFJUPMF-UHFFFAOYSA-N CCOC(CN(C(C=CC=C1)=C1N1C(OC(C)(C)C)=O)C1=O)=O Chemical compound CCOC(CN(C(C=CC=C1)=C1N1C(OC(C)(C)C)=O)C1=O)=O ULGAWHNZFJUPMF-UHFFFAOYSA-N 0.000 description 2
- CWTMDNDVICVSQQ-UHFFFAOYSA-N CN(C(C=C(C=C1)Cl)=C1N1CC2=CC(OC)=CC=C2)C1=O Chemical compound CN(C(C=C(C=C1)Cl)=C1N1CC2=CC(OC)=CC=C2)C1=O CWTMDNDVICVSQQ-UHFFFAOYSA-N 0.000 description 2
- YVBDGTFNTYXPJD-UHFFFAOYSA-N CN(C)C(CC1=CC=C(CN(C(C=CC=C2)=C2N2)C2=O)N=C1)=O Chemical compound CN(C)C(CC1=CC=C(CN(C(C=CC=C2)=C2N2)C2=O)N=C1)=O YVBDGTFNTYXPJD-UHFFFAOYSA-N 0.000 description 2
- NFILGHIGKDKONB-UHFFFAOYSA-N CN1C(CC2=CC=C(CN(C(C=CC=C3)=C3N3)C3=O)C=C2)=NN=C1 Chemical compound CN1C(CC2=CC=C(CN(C(C=CC=C3)=C3N3)C3=O)C=C2)=NN=C1 NFILGHIGKDKONB-UHFFFAOYSA-N 0.000 description 2
- FMCUVJJFITUSAF-UHFFFAOYSA-N CNC(C(CCC1=C2)C1=CC=C2Br)=O Chemical compound CNC(C(CCC1=C2)C1=CC=C2Br)=O FMCUVJJFITUSAF-UHFFFAOYSA-N 0.000 description 2
- CLQHUVLETSPAMW-UHFFFAOYSA-N COC(C1=CC=C(CN2C(Cl)=NC3=C2C=CC=C3)C=C1)=O Chemical compound COC(C1=CC=C(CN2C(Cl)=NC3=C2C=CC=C3)C=C1)=O CLQHUVLETSPAMW-UHFFFAOYSA-N 0.000 description 2
- MOZFRYYSOZSZKC-UHFFFAOYSA-N COC1=CC=CC=C1CNC1=C(C)C=CC=C1N Chemical compound COC1=CC=CC=C1CNC1=C(C)C=CC=C1N MOZFRYYSOZSZKC-UHFFFAOYSA-N 0.000 description 2
- UZVXWXPGXCSHEL-UHFFFAOYSA-N COc1cccc(Cn2c3ccc(Cl)cc3[nH]c2=O)c1 Chemical compound COc1cccc(Cn2c3ccc(Cl)cc3[nH]c2=O)c1 UZVXWXPGXCSHEL-UHFFFAOYSA-N 0.000 description 2
- KYSFLLNLZVKFAJ-UHFFFAOYSA-N COc1ccccc1Cn1c2c(C)cccc2[nH]c1=O Chemical compound COc1ccccc1Cn1c2c(C)cccc2[nH]c1=O KYSFLLNLZVKFAJ-UHFFFAOYSA-N 0.000 description 2
- JMVSQNVTOMTRDZ-UHFFFAOYSA-N COc1ccccc1Cn1c2cc(C)ccc2[nH]c1=O Chemical compound COc1ccccc1Cn1c2cc(C)ccc2[nH]c1=O JMVSQNVTOMTRDZ-UHFFFAOYSA-N 0.000 description 2
- CWVLXLJSGFKURY-UHFFFAOYSA-N COc1ccccc1Cn1c2cccc(C)c2[nH]c1=O Chemical compound COc1ccccc1Cn1c2cccc(C)c2[nH]c1=O CWVLXLJSGFKURY-UHFFFAOYSA-N 0.000 description 2
- REZMEZNBEDIBJE-UHFFFAOYSA-N CS(NCC1=CC=C(CN(C(C=CC=C2)=C2N2)C2=O)C=C1)(=O)=O Chemical compound CS(NCC1=CC=C(CN(C(C=CC=C2)=C2N2)C2=O)C=C1)(=O)=O REZMEZNBEDIBJE-UHFFFAOYSA-N 0.000 description 2
- MDGPZJUYOMAWMY-UHFFFAOYSA-N CS(NCC1=CC=C(CN(C(C=CC=C2)=C2N2)C2=O)S1)(=O)=O Chemical compound CS(NCC1=CC=C(CN(C(C=CC=C2)=C2N2)C2=O)S1)(=O)=O MDGPZJUYOMAWMY-UHFFFAOYSA-N 0.000 description 2
- JZERUXGVUDSCNJ-GFCCVEGCSA-N C[C@H](C1=CC=C(CN(C(C=CC=C2)=C2N2)C2=O)C=C1)NC(C)=O Chemical compound C[C@H](C1=CC=C(CN(C(C=CC=C2)=C2N2)C2=O)C=C1)NC(C)=O JZERUXGVUDSCNJ-GFCCVEGCSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 229940124087 DNA topoisomerase II inhibitor Drugs 0.000 description 2
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 2
- 206010014733 Endometrial cancer Diseases 0.000 description 2
- 206010014759 Endometrial neoplasm Diseases 0.000 description 2
- ADWBTAKDBGJMGY-UHFFFAOYSA-N FC(N1C(Cl)=NC2=C1C=CC=C2)F Chemical compound FC(N1C(Cl)=NC2=C1C=CC=C2)F ADWBTAKDBGJMGY-UHFFFAOYSA-N 0.000 description 2
- MHGOKZGIFPZTAN-UHFFFAOYSA-N Fc1cccc2n(Cc3ccccc3)c(=O)[nH]c12 Chemical compound Fc1cccc2n(Cc3ccccc3)c(=O)[nH]c12 MHGOKZGIFPZTAN-UHFFFAOYSA-N 0.000 description 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 2
- 206010018691 Granuloma Diseases 0.000 description 2
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 2
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 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
- 239000005511 L01XE05 - Sorafenib Substances 0.000 description 2
- 229910010082 LiAlH Inorganic materials 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- 238000006751 Mitsunobu reaction Methods 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 208000034578 Multiple myelomas Diseases 0.000 description 2
- AAQRDDRZMAABGH-UHFFFAOYSA-N N#CC1=NNC2=CC=C(CN(C(C=CC=C3)=C3N3)C3=O)C=C12 Chemical compound N#CC1=NNC2=CC=C(CN(C(C=CC=C3)=C3N3)C3=O)C=C12 AAQRDDRZMAABGH-UHFFFAOYSA-N 0.000 description 2
- AYDMQXIHPDLPJW-UHFFFAOYSA-N N-[(5-bromothiophen-2-yl)methyl]methanesulfonamide Chemical compound CS(=O)(=O)NCC1=CC=C(Br)S1 AYDMQXIHPDLPJW-UHFFFAOYSA-N 0.000 description 2
- HDNXOPMPKJQSMU-UHFFFAOYSA-N N-[[4-[(6-methyl-2-oxo-3H-benzimidazol-1-yl)methyl]phenyl]methyl]acetamide Chemical compound CC(NCC1=CC=C(CN(C(C=C(C)C=C2)=C2N2)C2=O)C=C1)=O HDNXOPMPKJQSMU-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- VGENCIYYXMGGNT-UHFFFAOYSA-N N-methyl-5-[(2-oxo-3H-benzimidazol-1-yl)methyl]thiophene-3-carboxamide Chemical compound CNC(C1=CSC(CN(C(C=CC=C2)=C2N2)C2=O)=C1)=O VGENCIYYXMGGNT-UHFFFAOYSA-N 0.000 description 2
- UWULWHYOXUFFHM-UHFFFAOYSA-N N-methyl-N-[[4-[(2-oxo-3H-benzimidazol-1-yl)methyl]phenyl]methyl]cyclopropanesulfonamide Chemical compound CN(CC1=CC=C(CN(C(C=CC=C2)=C2N2)C2=O)C=C1)S(C1CC1)(=O)=O UWULWHYOXUFFHM-UHFFFAOYSA-N 0.000 description 2
- AFUMCIZTONAGGP-UHFFFAOYSA-N NC1C2=CC(CN(C(C=CC=C3)=C3N3)C3=O)=CC=C2CC1 Chemical compound NC1C2=CC(CN(C(C=CC=C3)=C3N3)C3=O)=CC=C2CC1 AFUMCIZTONAGGP-UHFFFAOYSA-N 0.000 description 2
- VNQIKZFXSYYFBP-UHFFFAOYSA-N NCC(C=CC(CN(C1=CC=CC=C1N1)C1=O)=C1)=C1Cl Chemical compound NCC(C=CC(CN(C1=CC=CC=C1N1)C1=O)=C1)=C1Cl VNQIKZFXSYYFBP-UHFFFAOYSA-N 0.000 description 2
- KJSLFNFJIDSOIJ-UHFFFAOYSA-N NCC1=CC=C(CN(C(C=C(C=C2)Cl)=C2N2)C2=O)C=C1 Chemical compound NCC1=CC=C(CN(C(C=C(C=C2)Cl)=C2N2)C2=O)C=C1 KJSLFNFJIDSOIJ-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- LDLVWXMLANIQIJ-UHFFFAOYSA-N O=C1N(CC(CC2)CCN2C2=CC=CC=N2)C(C=CC=C2)=C2N1 Chemical compound O=C1N(CC(CC2)CCN2C2=CC=CC=N2)C(C=CC=C2)=C2N1 LDLVWXMLANIQIJ-UHFFFAOYSA-N 0.000 description 2
- DIIUIJLTYRBXBL-UHFFFAOYSA-N O=C1N(CC(SC(CN(C(C=CC=C2)=C2N2)C2=O)=C2)=C2Cl)CCC1 Chemical compound O=C1N(CC(SC(CN(C(C=CC=C2)=C2N2)C2=O)=C2)=C2Cl)CCC1 DIIUIJLTYRBXBL-UHFFFAOYSA-N 0.000 description 2
- ZOTAURFQHSEEMH-UHFFFAOYSA-N O=C1N(CC2=CC=C(CC3=NN=CO3)C=C2)C(C=CC=C2)=C2N1 Chemical compound O=C1N(CC2=CC=C(CC3=NN=CO3)C=C2)C(C=CC=C2)=C2N1 ZOTAURFQHSEEMH-UHFFFAOYSA-N 0.000 description 2
- PQRXNTZJYBRPHQ-UHFFFAOYSA-N O=C1N(CC2=CC=C(CN(C(C=C(C=C3)F)=C3N3)C3=O)C=C2)CCC1 Chemical compound O=C1N(CC2=CC=C(CN(C(C=C(C=C3)F)=C3N3)C3=O)C=C2)CCC1 PQRXNTZJYBRPHQ-UHFFFAOYSA-N 0.000 description 2
- SHOFYBUGNOTADV-UHFFFAOYSA-N O=C1N(CC2=CC=C(CN(C(C=CC=C3)=C3N3)C3=O)C=C2)CC=C1 Chemical compound O=C1N(CC2=CC=C(CN(C(C=CC=C3)=C3N3)C3=O)C=C2)CC=C1 SHOFYBUGNOTADV-UHFFFAOYSA-N 0.000 description 2
- MSGJBUJYGXSHBW-UHFFFAOYSA-N O=C1N(CC2=CC=C(CN(C(C=CC=C3)=C3N3)C3=O)C=C2)CCC1 Chemical compound O=C1N(CC2=CC=C(CN(C(C=CC=C3)=C3N3)C3=O)C=C2)CCC1 MSGJBUJYGXSHBW-UHFFFAOYSA-N 0.000 description 2
- IGMKUQWYVIVIPU-UHFFFAOYSA-N O=C1N(CC2=CC=C(CN(C(C=CC=C3)=C3N3)C3=O)C=C2)CCC1(F)F Chemical compound O=C1N(CC2=CC=C(CN(C(C=CC=C3)=C3N3)C3=O)C=C2)CCC1(F)F IGMKUQWYVIVIPU-UHFFFAOYSA-N 0.000 description 2
- MEZNDLNNNAKRCK-UHFFFAOYSA-N O=C1N(CC2=CC=C(CN3C(Cl)=NC(C=C4)=C3C=C4F)C=C2)CCC1 Chemical compound O=C1N(CC2=CC=C(CN3C(Cl)=NC(C=C4)=C3C=C4F)C=C2)CCC1 MEZNDLNNNAKRCK-UHFFFAOYSA-N 0.000 description 2
- ZFRJOMKAXDYLCM-UHFFFAOYSA-N O=C1N(CC2=CC=C(CN3N=NC=C3)C=C2)C(C=CC=C2)=C2N1 Chemical compound O=C1N(CC2=CC=C(CN3N=NC=C3)C=C2)C(C=CC=C2)=C2N1 ZFRJOMKAXDYLCM-UHFFFAOYSA-N 0.000 description 2
- RBVJQDXUKVLYGZ-UHFFFAOYSA-N O=C1N(CC2=CC=C3NCCC3=C2)C(C=CC=C2)=C2N1 Chemical compound O=C1N(CC2=CC=C3NCCC3=C2)C(C=CC=C2)=C2N1 RBVJQDXUKVLYGZ-UHFFFAOYSA-N 0.000 description 2
- VRWWCDDNBIEVMY-UHFFFAOYSA-N OC(CC1=CC(CN(C(C=CC=C2)=C2N2)C2=O)=CC=C1)=O Chemical compound OC(CC1=CC(CN(C(C=CC=C2)=C2N2)C2=O)=CC=C1)=O VRWWCDDNBIEVMY-UHFFFAOYSA-N 0.000 description 2
- DJNBGDHUHFIEHZ-UHFFFAOYSA-N OCC1=CN=NN1CC1=CC=C(CN(C2=CC=CC=C2N2)C2=O)C=C1 Chemical compound OCC1=CN=NN1CC1=CC=C(CN(C2=CC=CC=C2N2)C2=O)C=C1 DJNBGDHUHFIEHZ-UHFFFAOYSA-N 0.000 description 2
- 240000007594 Oryza sativa Species 0.000 description 2
- 235000007164 Oryza sativa Nutrition 0.000 description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
- SHGAZHPCJJPHSC-UHFFFAOYSA-N Panrexin Chemical compound OC(=O)C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 description 2
- YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical compound [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 description 2
- 241000720974 Protium Species 0.000 description 2
- 208000004337 Salivary Gland Neoplasms Diseases 0.000 description 2
- 206010061934 Salivary gland cancer Diseases 0.000 description 2
- 206010041067 Small cell lung cancer Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- NAVMQTYZDKMPEU-UHFFFAOYSA-N Targretin Chemical compound CC1=CC(C(CCC2(C)C)(C)C)=C2C=C1C(=C)C1=CC=C(C(O)=O)C=C1 NAVMQTYZDKMPEU-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 239000000317 Topoisomerase II Inhibitor Substances 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 2
- LTCWQHRPZIUASK-UHFFFAOYSA-N [O-][N+](=O)C1=C(NCC2=CC=CC=C2)C=CC=C1N1CCCC1 Chemical compound [O-][N+](=O)C1=C(NCC2=CC=CC=C2)C=CC=C1N1CCCC1 LTCWQHRPZIUASK-UHFFFAOYSA-N 0.000 description 2
- 150000001242 acetic acid derivatives Chemical class 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 150000004716 alpha keto acids Chemical class 0.000 description 2
- 150000001413 amino acids Chemical group 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 230000000340 anti-metabolite Effects 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 229940100197 antimetabolite Drugs 0.000 description 2
- 239000002256 antimetabolite Substances 0.000 description 2
- 201000011165 anus cancer Diseases 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- RITAVMQDGBJQJZ-FMIVXFBMSA-N axitinib Chemical compound CNC(=O)C1=CC=CC=C1SC1=CC=C(C(\C=C\C=2N=CC=CC=2)=NN2)C2=C1 RITAVMQDGBJQJZ-FMIVXFBMSA-N 0.000 description 2
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- 150000007514 bases Chemical class 0.000 description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 2
- 201000009036 biliary tract cancer Diseases 0.000 description 2
- 208000020790 biliary tract neoplasm Diseases 0.000 description 2
- LTEJRLHKIYCEOX-OCCSQVGLSA-N brivanib alaninate Chemical compound C1=C2NC(C)=CC2=C(F)C(OC2=NC=NN3C=C(C(=C32)C)OC[C@@H](C)OC(=O)[C@H](C)N)=C1 LTEJRLHKIYCEOX-OCCSQVGLSA-N 0.000 description 2
- 229950005993 brivanib alaninate Drugs 0.000 description 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 2
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 2
- 229960002436 cladribine Drugs 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 229960000684 cytarabine Drugs 0.000 description 2
- 229960000640 dactinomycin Drugs 0.000 description 2
- 229960000975 daunorubicin Drugs 0.000 description 2
- 238000006114 decarboxylation reaction Methods 0.000 description 2
- 229960003603 decitabine Drugs 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 229910052805 deuterium Inorganic materials 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229960005420 etoposide Drugs 0.000 description 2
- LIQODXNTTZAGID-OCBXBXKTSA-N etoposide phosphate Chemical compound COC1=C(OP(O)(O)=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 LIQODXNTTZAGID-OCBXBXKTSA-N 0.000 description 2
- 229960000752 etoposide phosphate Drugs 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- VWWQXMAJTJZDQX-UYBVJOGSSA-N flavin adenine dinucleotide Chemical compound C1=NC2=C(N)N=CN=C2N1[C@@H]([C@H](O)[C@@H]1O)O[C@@H]1CO[P@](O)(=O)O[P@@](O)(=O)OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C2=NC(=O)NC(=O)C2=NC2=C1C=C(C)C(C)=C2 VWWQXMAJTJZDQX-UYBVJOGSSA-N 0.000 description 2
- 235000019162 flavin adenine dinucleotide Nutrition 0.000 description 2
- 239000011714 flavin adenine dinucleotide Substances 0.000 description 2
- 229940093632 flavin-adenine dinucleotide Drugs 0.000 description 2
- ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 description 2
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 2
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
- 201000010536 head and neck cancer Diseases 0.000 description 2
- 208000014829 head and neck neoplasm Diseases 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 229940003183 hexalen Drugs 0.000 description 2
- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 229940099279 idamycin Drugs 0.000 description 2
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 229910052741 iridium Inorganic materials 0.000 description 2
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 2
- 125000005956 isoquinolyl group Chemical group 0.000 description 2
- 229960005280 isotretinoin Drugs 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000012669 liquid formulation Substances 0.000 description 2
- 208000014018 liver neoplasm Diseases 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229960004961 mechlorethamine Drugs 0.000 description 2
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 2
- 229960001924 melphalan Drugs 0.000 description 2
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 229960003058 methotrexate sodium Drugs 0.000 description 2
- WEAGRZSGSXTUMX-UHFFFAOYSA-N methyl 3-[(2-oxo-3H-benzimidazol-1-yl)methyl]benzoate Chemical compound O=C1NC2=C(N1CC=1C=C(C(=O)OC)C=CC=1)C=CC=C2 WEAGRZSGSXTUMX-UHFFFAOYSA-N 0.000 description 2
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 229960004857 mitomycin Drugs 0.000 description 2
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- RAHBGWKEPAQNFF-UHFFFAOYSA-N motesanib Chemical compound C=1C=C2C(C)(C)CNC2=CC=1NC(=O)C1=CC=CN=C1NCC1=CC=NC=C1 RAHBGWKEPAQNFF-UHFFFAOYSA-N 0.000 description 2
- BXQVPYPFMGGFNE-UHFFFAOYSA-N n-(thiophen-2-ylmethyl)methanesulfonamide Chemical compound CS(=O)(=O)NCC1=CC=CS1 BXQVPYPFMGGFNE-UHFFFAOYSA-N 0.000 description 2
- DRRCKKJEBGEBGR-SSDOTTSWSA-N n-[(1r)-1-(4-bromophenyl)ethyl]acetamide Chemical compound CC(=O)N[C@H](C)C1=CC=C(Br)C=C1 DRRCKKJEBGEBGR-SSDOTTSWSA-N 0.000 description 2
- CTEYBASDYOQWIP-UHFFFAOYSA-N n-[(4-bromophenyl)methyl]prop-2-en-1-amine Chemical compound BrC1=CC=C(CNCC=C)C=C1 CTEYBASDYOQWIP-UHFFFAOYSA-N 0.000 description 2
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 2
- 210000000581 natural killer T-cell Anatomy 0.000 description 2
- 229910052759 nickel Inorganic materials 0.000 description 2
- 125000006574 non-aromatic ring group Chemical group 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 229940127084 other anti-cancer agent Drugs 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- WBXPDJSOTKVWSJ-ZDUSSCGKSA-L pemetrexed(2-) Chemical compound C=1NC=2NC(N)=NC(=O)C=2C=1CCC1=CC=C(C(=O)N[C@@H](CCC([O-])=O)C([O-])=O)C=C1 WBXPDJSOTKVWSJ-ZDUSSCGKSA-L 0.000 description 2
- FPVKHBSQESCIEP-JQCXWYLXSA-N pentostatin Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC[C@H]2O)=C2N=C1 FPVKHBSQESCIEP-JQCXWYLXSA-N 0.000 description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 2
- 238000010837 poor prognosis Methods 0.000 description 2
- 235000015320 potassium carbonate Nutrition 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 2
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 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
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 2
- 125000005493 quinolyl group Chemical group 0.000 description 2
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 2
- 108091006082 receptor inhibitors Proteins 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- HSSLDCABUXLXKM-UHFFFAOYSA-N resorufin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3N=C21 HSSLDCABUXLXKM-UHFFFAOYSA-N 0.000 description 2
- 235000009566 rice Nutrition 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- BNRNXUUZRGQAQC-UHFFFAOYSA-N sildenafil Chemical compound CCCC1=NN(C)C(C(N2)=O)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 BNRNXUUZRGQAQC-UHFFFAOYSA-N 0.000 description 2
- 208000000587 small cell lung carcinoma Diseases 0.000 description 2
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 229960004964 temozolomide Drugs 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- DOHFMHDCAVSAAH-UHFFFAOYSA-N tert-butyl 4-[(2-oxo-3h-benzimidazol-1-yl)methyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CN1C(=O)NC2=CC=CC=C21 DOHFMHDCAVSAAH-UHFFFAOYSA-N 0.000 description 2
- XDJCYKMWJCYQJM-UHFFFAOYSA-N tert-butyl n-(3-hydroxypropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCO XDJCYKMWJCYQJM-UHFFFAOYSA-N 0.000 description 2
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 229960001727 tretinoin Drugs 0.000 description 2
- 125000004306 triazinyl group Chemical group 0.000 description 2
- 125000001425 triazolyl group Chemical group 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 2
- 201000005112 urinary bladder cancer Diseases 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- SOZMSEPDYJGBEK-ZCFIWIBFSA-N (1r)-1-(4-bromophenyl)ethanamine Chemical compound C[C@@H](N)C1=CC=C(Br)C=C1 SOZMSEPDYJGBEK-ZCFIWIBFSA-N 0.000 description 1
- SIFCHNIAAPMMKG-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) acetate Chemical compound CC(=O)ON1C(=O)CCC1=O SIFCHNIAAPMMKG-UHFFFAOYSA-N 0.000 description 1
- PXJACNDVRNAFHD-UHFFFAOYSA-N (2-methoxyphenyl)methanamine Chemical compound COC1=CC=CC=C1CN PXJACNDVRNAFHD-UHFFFAOYSA-N 0.000 description 1
- VQJGUUHKSTYEGE-GCYSTPHZSA-N (2S,4R)-4-hydroxypyrrolidine-2-carboxylic acid Chemical compound N1[C@H](C(=O)O)C[C@@H](O)C1.N1[C@H](C(=O)O)C[C@@H](O)C1.N1[C@H](C(=O)O)C[C@@H](O)C1 VQJGUUHKSTYEGE-GCYSTPHZSA-N 0.000 description 1
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 1
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- CRDQDMSHRCFAAW-UHFFFAOYSA-N (4-bromo-2-methylphenyl)methanamine Chemical compound CC1=CC(Br)=CC=C1CN CRDQDMSHRCFAAW-UHFFFAOYSA-N 0.000 description 1
- VNTHYLVDGVBPOU-QQYBVWGSSA-N (7s,9s)-9-acetyl-7-[(2r,4s,5s,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.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 VNTHYLVDGVBPOU-QQYBVWGSSA-N 0.000 description 1
- GMVPRGQOIOIIMI-UHFFFAOYSA-N (8R,11R,12R,13E,15S)-11,15-Dihydroxy-9-oxo-13-prostenoic acid Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CCCCCCC(O)=O GMVPRGQOIOIIMI-UHFFFAOYSA-N 0.000 description 1
- FPVKHBSQESCIEP-UHFFFAOYSA-N (8S)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol Natural products C1C(O)C(CO)OC1N1C(NC=NCC2O)=C2N=C1 FPVKHBSQESCIEP-UHFFFAOYSA-N 0.000 description 1
- NDAUXUAQIAJITI-LBPRGKRZSA-N (R)-salbutamol Chemical compound CC(C)(C)NC[C@H](O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-LBPRGKRZSA-N 0.000 description 1
- SSNCMIDZGFCTST-UHFFFAOYSA-N 1,3-difluoro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=C(F)C=CC=C1F SSNCMIDZGFCTST-UHFFFAOYSA-N 0.000 description 1
- AAAXMNYUNVCMCJ-UHFFFAOYSA-N 1,3-diiodopropane Chemical compound ICCCI AAAXMNYUNVCMCJ-UHFFFAOYSA-N 0.000 description 1
- BACZSVQZBSCWIG-UHFFFAOYSA-N 1-(bromomethyl)-3-iodobenzene Chemical compound BrCC1=CC=CC(I)=C1 BACZSVQZBSCWIG-UHFFFAOYSA-N 0.000 description 1
- KDDVZGFLGMXKRC-UHFFFAOYSA-N 1-(bromomethyl)-3-propan-2-yloxybenzene Chemical compound CC(C)OC1=CC=CC(CBr)=C1 KDDVZGFLGMXKRC-UHFFFAOYSA-N 0.000 description 1
- NMERHTBBQWPUKW-UHFFFAOYSA-N 1-(bromomethyl)cyclobutane-1-carbonitrile Chemical compound BrCC1(CCC1)C#N NMERHTBBQWPUKW-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- OPNDWCQXQKASBM-UHFFFAOYSA-N 1-[(5-bromopyridin-2-yl)methyl]pyrrolidin-2-one Chemical compound Brc1ccc(CN2CCCC2=O)nc1 OPNDWCQXQKASBM-UHFFFAOYSA-N 0.000 description 1
- UJFLOGKNXJHMIM-UHFFFAOYSA-N 1-[[4-(hydroxymethyl)phenyl]methyl]pyrrolidin-2-one Chemical compound C1=CC(CO)=CC=C1CN1C(=O)CCC1 UJFLOGKNXJHMIM-UHFFFAOYSA-N 0.000 description 1
- QRADKVYIJIAENZ-UHFFFAOYSA-N 1-[[bromo(difluoro)methyl]-ethoxyphosphoryl]oxyethane Chemical compound CCOP(=O)(C(F)(F)Br)OCC QRADKVYIJIAENZ-UHFFFAOYSA-N 0.000 description 1
- DHHMIFLTUKSPEV-UHFFFAOYSA-N 1-benzyl-3H-thieno[2,3-d]imidazol-2-one Chemical compound O=C1NC=2SC=CC=2N1CC1=CC=CC=C1 DHHMIFLTUKSPEV-UHFFFAOYSA-N 0.000 description 1
- JMSUNAQVHOHLMX-UHFFFAOYSA-N 1-cyclohexylethanol Chemical compound CC(O)C1CCCCC1 JMSUNAQVHOHLMX-UHFFFAOYSA-N 0.000 description 1
- JSXAJLMUBSEJFF-UHFFFAOYSA-N 1-fluoro-3-methyl-2-nitrobenzene Chemical compound CC1=CC=CC(F)=C1[N+]([O-])=O JSXAJLMUBSEJFF-UHFFFAOYSA-N 0.000 description 1
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 1
- WAPNOHKVXSQRPX-UHFFFAOYSA-N 1-phenylethanol Chemical compound CC(O)C1=CC=CC=C1 WAPNOHKVXSQRPX-UHFFFAOYSA-N 0.000 description 1
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 1
- NMIZONYLXCOHEF-UHFFFAOYSA-N 1h-imidazole-2-carboxamide Chemical compound NC(=O)C1=NC=CN1 NMIZONYLXCOHEF-UHFFFAOYSA-N 0.000 description 1
- JJVNSSFYOJOECV-UHFFFAOYSA-N 2,3-dihydro-1h-inden-5-ylmethanamine Chemical compound NCC1=CC=C2CCCC2=C1 JJVNSSFYOJOECV-UHFFFAOYSA-N 0.000 description 1
- RJXOVESYJFXCGI-UHFFFAOYSA-N 2,4-difluoro-1-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1F RJXOVESYJFXCGI-UHFFFAOYSA-N 0.000 description 1
- WKAUICDGONASOP-UHFFFAOYSA-N 2-(3-bromophenyl)-1,3,4-oxadiazole Chemical compound BrC1=CC=CC(C=2OC=NN=2)=C1 WKAUICDGONASOP-UHFFFAOYSA-N 0.000 description 1
- KBGMAXNDJAGTDD-UHFFFAOYSA-N 2-(bromomethyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical compound CC1(C)OB(CBr)OC1(C)C KBGMAXNDJAGTDD-UHFFFAOYSA-N 0.000 description 1
- TYLGBYPNRCBPLB-UHFFFAOYSA-N 2-[(4-bromophenyl)methyl]-1,2-thiazolidine 1,1-dioxide Chemical compound C1=CC(Br)=CC=C1CN1S(=O)(=O)CCC1 TYLGBYPNRCBPLB-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- VQFRIIZTQOGROW-UHFFFAOYSA-N 2-bromo-1-chloro-4-ethylbenzene Chemical compound CCC1=CC=C(Cl)C(Br)=C1 VQFRIIZTQOGROW-UHFFFAOYSA-N 0.000 description 1
- YLMFXCIATJJKQL-UHFFFAOYSA-N 2-bromo-4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1Br YLMFXCIATJJKQL-UHFFFAOYSA-N 0.000 description 1
- JHNQWIWQZVUGOB-UHFFFAOYSA-N 2-bromo-5-(bromomethyl)-3-chloropyridine Chemical compound ClC1=CC(CBr)=CN=C1Br JHNQWIWQZVUGOB-UHFFFAOYSA-N 0.000 description 1
- YWNJQQNBJQUKME-UHFFFAOYSA-N 2-bromo-5-methylpyridine Chemical compound CC1=CC=C(Br)N=C1 YWNJQQNBJQUKME-UHFFFAOYSA-N 0.000 description 1
- UZIXQYXXJBMILL-UHFFFAOYSA-N 2-chloro-6-fluoro-1h-benzimidazole Chemical compound FC1=CC=C2NC(Cl)=NC2=C1 UZIXQYXXJBMILL-UHFFFAOYSA-N 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- 229940013085 2-diethylaminoethanol Drugs 0.000 description 1
- NBCNUIXYBLFJMI-UHFFFAOYSA-N 2-fluoro-1-methyl-3-nitrobenzene Chemical compound CC1=CC=CC([N+]([O-])=O)=C1F NBCNUIXYBLFJMI-UHFFFAOYSA-N 0.000 description 1
- MTAODLNXWYIKSO-UHFFFAOYSA-N 2-fluoropyridine Chemical compound FC1=CC=CC=N1 MTAODLNXWYIKSO-UHFFFAOYSA-N 0.000 description 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- GWZDNKPGIKSZBI-UHFFFAOYSA-N 2-nitro-N-(3-quinolin-8-yloxypropyl)aniline Chemical compound [O-][N+](=O)C1=CC=CC=C1NCCCOC1=CC=CC2=CC=CN=C12 GWZDNKPGIKSZBI-UHFFFAOYSA-N 0.000 description 1
- BDHHIGBFEDVNDX-UHFFFAOYSA-N 3,3-difluoropyrrolidin-2-one Chemical compound FC1(F)CCNC1=O BDHHIGBFEDVNDX-UHFFFAOYSA-N 0.000 description 1
- LGDIZEGOZFNYLJ-UHFFFAOYSA-N 3-(benzylamino)thiophene-2-carbonyl azide Chemical compound S1C=CC(NCC=2C=CC=CC=2)=C1C(=O)N=[N+]=[N-] LGDIZEGOZFNYLJ-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- CQSJDKGNONPQOQ-UHFFFAOYSA-N 3-aminothiophene-2-carboxylic acid Chemical compound NC=1C=CSC=1C(O)=O CQSJDKGNONPQOQ-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
- ALKYHXVLJMQRLQ-UHFFFAOYSA-M 3-carboxynaphthalen-2-olate Chemical compound C1=CC=C2C=C(C([O-])=O)C(O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-M 0.000 description 1
- PYEHNKXDXBNHQQ-UHFFFAOYSA-N 3-methyl-1h-benzimidazol-2-one Chemical compound C1=CC=C2N(C)C(O)=NC2=C1 PYEHNKXDXBNHQQ-UHFFFAOYSA-N 0.000 description 1
- XFASJWLBXHWUMW-UHFFFAOYSA-N 3-prop-1-en-2-yl-1h-benzimidazol-2-one Chemical compound C1=CC=C2NC(=O)N(C(=C)C)C2=C1 XFASJWLBXHWUMW-UHFFFAOYSA-N 0.000 description 1
- 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 1
- DYPSDTOQOSPYOT-UHFFFAOYSA-N 4-bromo-1-(bromomethyl)-2-chlorobenzene Chemical compound ClC1=CC(Br)=CC=C1CBr DYPSDTOQOSPYOT-UHFFFAOYSA-N 0.000 description 1
- TWBFZKKJFREYES-UHFFFAOYSA-N 4-bromo-3-methoxybenzonitrile Chemical compound COC1=CC(C#N)=CC=C1Br TWBFZKKJFREYES-UHFFFAOYSA-N 0.000 description 1
- HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 1
- KWEWNOOZQVJONF-UHFFFAOYSA-N 4-fluorobenzene-1,2-diamine Chemical compound NC1=CC=C(F)C=C1N KWEWNOOZQVJONF-UHFFFAOYSA-N 0.000 description 1
- NMUSYJAQQFHJEW-UHFFFAOYSA-N 5-Azacytidine Natural products O=C1N=C(N)N=CN1C1C(O)C(O)C(CO)O1 NMUSYJAQQFHJEW-UHFFFAOYSA-N 0.000 description 1
- QIULWQLXNFSZJG-UHFFFAOYSA-N 5-bromo-1h-indazole-3-carbonitrile Chemical compound BrC1=CC=C2NN=C(C#N)C2=C1 QIULWQLXNFSZJG-UHFFFAOYSA-N 0.000 description 1
- RHHOBLZUVLGGBU-UHFFFAOYSA-N 5-bromo-2,3-dihydro-1h-indene-1-carboxylic acid Chemical compound BrC1=CC=C2C(C(=O)O)CCC2=C1 RHHOBLZUVLGGBU-UHFFFAOYSA-N 0.000 description 1
- PKCHRWPMNDRVMI-UHFFFAOYSA-N 5-bromo-2-(bromomethyl)pyridine Chemical compound BrCC1=CC=C(Br)C=N1 PKCHRWPMNDRVMI-UHFFFAOYSA-N 0.000 description 1
- DUUPWFRCVBAIKZ-UHFFFAOYSA-N 5-bromo-3-chlorothiophene-2-carboxylic acid Chemical compound OC(=O)C=1SC(Br)=CC=1Cl DUUPWFRCVBAIKZ-UHFFFAOYSA-N 0.000 description 1
- NIXUUECXYHZKTI-UHFFFAOYSA-N 5-bromo-3-methylthiophene-2-carbaldehyde Chemical compound CC=1C=C(Br)SC=1C=O NIXUUECXYHZKTI-UHFFFAOYSA-N 0.000 description 1
- YCNXGPMGMAKDPM-UHFFFAOYSA-N 5-bromothiophene-3-carboxylic acid Chemical compound OC(=O)C1=CSC(Br)=C1 YCNXGPMGMAKDPM-UHFFFAOYSA-N 0.000 description 1
- FUHDZKNBAPRMHD-UHFFFAOYSA-N 6-bromo-2,3-dihydro-1-benzothiophene 1,1-dioxide Chemical compound BrC1=CC=C2CCS(=O)(=O)C2=C1 FUHDZKNBAPRMHD-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- SHGAZHPCJJPHSC-ZVCIMWCZSA-N 9-cis-retinoic acid Chemical compound OC(=O)/C=C(\C)/C=C/C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-ZVCIMWCZSA-N 0.000 description 1
- OSDWBNJEKMUWAV-UHFFFAOYSA-N Allyl chloride Chemical compound ClCC=C OSDWBNJEKMUWAV-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 101100452478 Arabidopsis thaliana DHAD gene Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
- 108091008875 B cell receptors Proteins 0.000 description 1
- 239000005552 B01AC04 - Clopidogrel Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 239000012388 BrettPhos 3rd generation precatalyst Substances 0.000 description 1
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 description 1
- ZZOZEPSYNBOIHV-UHFFFAOYSA-N C1=CC(CN)=CC=C1CN1C(=O)NC2=CC=C(F)C=C21 Chemical compound C1=CC(CN)=CC=C1CN1C(=O)NC2=CC=C(F)C=C21 ZZOZEPSYNBOIHV-UHFFFAOYSA-N 0.000 description 1
- UJEGJQBUWQWAOZ-UHFFFAOYSA-N CC(C)(C)OC(N(C(C=C(C=C1)Cl)=C1N1CC2=CC(OC)=CC=C2)C1=O)=O Chemical compound CC(C)(C)OC(N(C(C=C(C=C1)Cl)=C1N1CC2=CC(OC)=CC=C2)C1=O)=O UJEGJQBUWQWAOZ-UHFFFAOYSA-N 0.000 description 1
- YXQQHIILKHHGDW-UHFFFAOYSA-N CC(C)(C)OC(N(C(C=CC(F)=C1)=C1N1CC2=CC=C(CC(OC)=O)C=C2)C1=O)=O Chemical compound CC(C)(C)OC(N(C(C=CC(F)=C1)=C1N1CC2=CC=C(CC(OC)=O)C=C2)C1=O)=O YXQQHIILKHHGDW-UHFFFAOYSA-N 0.000 description 1
- YQZCHFKWTKWZTR-UHFFFAOYSA-N CC(C)(C)OC(N(C(C=CC=C1)=C1N1CC(C=CC(CNC(C)=O)=C2)=C2OC)C1=O)=O Chemical compound CC(C)(C)OC(N(C(C=CC=C1)=C1N1CC(C=CC(CNC(C)=O)=C2)=C2OC)C1=O)=O YQZCHFKWTKWZTR-UHFFFAOYSA-N 0.000 description 1
- QXYHPINYDPIZBX-UHFFFAOYSA-N CC(C)(C)OC(N(C(C=CC=C1)=C1N1CC(C=N2)=CC(Cl)=C2Br)C1=O)=O Chemical compound CC(C)(C)OC(N(C(C=CC=C1)=C1N1CC(C=N2)=CC(Cl)=C2Br)C1=O)=O QXYHPINYDPIZBX-UHFFFAOYSA-N 0.000 description 1
- UFIYZAYFOQLHQE-UHFFFAOYSA-N CC(C)(C)OC(N(C(C=CC=C1)=C1N1CC2=CC=C(CNS(C)(=O)=O)S2)C1=O)=O Chemical compound CC(C)(C)OC(N(C(C=CC=C1)=C1N1CC2=CC=C(CNS(C)(=O)=O)S2)C1=O)=O UFIYZAYFOQLHQE-UHFFFAOYSA-N 0.000 description 1
- GEPGHERCOSASRT-UHFFFAOYSA-N CC(C)(C)OC(NCC(C=CC(CN(C(C=CC=C1)=C1N1)C1=O)=C1)=C1Cl)=O Chemical compound CC(C)(C)OC(NCC(C=CC(CN(C(C=CC=C1)=C1N1)C1=O)=C1)=C1Cl)=O GEPGHERCOSASRT-UHFFFAOYSA-N 0.000 description 1
- VEUTUVCVXMKUKO-UHFFFAOYSA-N CC(C)(C)OC(NCC1=CC=C(CN(C(C=C(C=C2)F)=C2N2)C2=O)C=C1)=O Chemical compound CC(C)(C)OC(NCC1=CC=C(CN(C(C=C(C=C2)F)=C2N2)C2=O)C=C1)=O VEUTUVCVXMKUKO-UHFFFAOYSA-N 0.000 description 1
- BHZRDZSYRKNUOD-UHFFFAOYSA-N CC(C)(C)OC(NCC1=CC=C(CN(C(C=CC=C2)=C2N2)C2=O)C=C1)=O Chemical compound CC(C)(C)OC(NCC1=CC=C(CN(C(C=CC=C2)=C2N2)C2=O)C=C1)=O BHZRDZSYRKNUOD-UHFFFAOYSA-N 0.000 description 1
- XXHFEHZESMEWAX-UHFFFAOYSA-N CC(C)(C)OC(NCC1=CC=C(CNC(C=C(C=C2)F)=C2N)C=C1)=O Chemical compound CC(C)(C)OC(NCC1=CC=C(CNC(C=C(C=C2)F)=C2N)C=C1)=O XXHFEHZESMEWAX-UHFFFAOYSA-N 0.000 description 1
- ORBODSXIFXNQJU-UHFFFAOYSA-N CC(C)OC1=CC=CC(CN(C2=CC=CC=C2N2)C2=O)=C1 Chemical compound CC(C)OC1=CC=CC(CN(C2=CC=CC=C2N2)C2=O)=C1 ORBODSXIFXNQJU-UHFFFAOYSA-N 0.000 description 1
- LHDUOZCKQFGPHC-UHFFFAOYSA-N CC(C1=CC=CC=C1)N(C(C=CC=C1)=C1N1C(OC(C)(C)C)=O)C1=O Chemical compound CC(C1=CC=CC=C1)N(C(C=CC=C1)=C1N1C(OC(C)(C)C)=O)C1=O LHDUOZCKQFGPHC-UHFFFAOYSA-N 0.000 description 1
- IPICLXINYVEEJQ-UHFFFAOYSA-N CC(C1CCCCC1)N(C(C=CC=C1)=C1N1C(OC(C)(C)C)=O)C1=O Chemical compound CC(C1CCCCC1)N(C(C=CC=C1)=C1N1C(OC(C)(C)C)=O)C1=O IPICLXINYVEEJQ-UHFFFAOYSA-N 0.000 description 1
- UCOPFRAMRGGOLV-UHFFFAOYSA-N CC(N(C(C=CC=C1)=C1N1CC2=CC=CC(C(OC)=O)=C2)C1=O)=C Chemical compound CC(N(C(C=CC=C1)=C1N1CC2=CC=CC(C(OC)=O)=C2)C1=O)=C UCOPFRAMRGGOLV-UHFFFAOYSA-N 0.000 description 1
- XMCWPCQSXHAWJM-UHFFFAOYSA-N CC(NCC(C=C1)=CC(OC)=C1Br)=O Chemical compound CC(NCC(C=C1)=CC(OC)=C1Br)=O XMCWPCQSXHAWJM-UHFFFAOYSA-N 0.000 description 1
- XGDBPUSSDDDZNL-UHFFFAOYSA-N CC(NCC(S1)=C(C)C=C1Br)=O Chemical compound CC(NCC(S1)=C(C)C=C1Br)=O XGDBPUSSDDDZNL-UHFFFAOYSA-N 0.000 description 1
- IHKRBWUJACNQCF-UHFFFAOYSA-N CC(NCC(SC(CN(C(C=CC=C1)=C1N1)C1=O)=C1)=C1Cl)=O Chemical compound CC(NCC(SC(CN(C(C=CC=C1)=C1N1)C1=O)=C1)=C1Cl)=O IHKRBWUJACNQCF-UHFFFAOYSA-N 0.000 description 1
- LWNVRCMRZOWHAE-UHFFFAOYSA-N CC(NCC(SC=C1)=C1Cl)=O Chemical compound CC(NCC(SC=C1)=C1Cl)=O LWNVRCMRZOWHAE-UHFFFAOYSA-N 0.000 description 1
- RJDDBZINBJFCMJ-UHFFFAOYSA-N CC(NCC1=CC=C(CN(C(C=C(C=C2)Cl)=C2N2)C2=O)C=C1)=O Chemical compound CC(NCC1=CC=C(CN(C(C=C(C=C2)Cl)=C2N2)C2=O)C=C1)=O RJDDBZINBJFCMJ-UHFFFAOYSA-N 0.000 description 1
- IUIFIZHMBSPFJQ-UHFFFAOYSA-N CC(NCC1=CC=C(CN(C(C=C(C=C2)Cl)=C2N2C(C)=O)C2=O)C=C1)=O Chemical compound CC(NCC1=CC=C(CN(C(C=C(C=C2)Cl)=C2N2C(C)=O)C2=O)C=C1)=O IUIFIZHMBSPFJQ-UHFFFAOYSA-N 0.000 description 1
- SUFBRSRXOYEVQQ-UHFFFAOYSA-N CC(NCC1=CC=C(CN(C(C=C(C=C2)F)=C2N2)C2=O)C=C1)=O Chemical compound CC(NCC1=CC=C(CN(C(C=C(C=C2)F)=C2N2)C2=O)C=C1)=O SUFBRSRXOYEVQQ-UHFFFAOYSA-N 0.000 description 1
- YXGDLEHGEBFFMR-UHFFFAOYSA-N CC1=C(CC(NN)=O)C=CC(Br)=C1 Chemical compound CC1=C(CC(NN)=O)C=CC(Br)=C1 YXGDLEHGEBFFMR-UHFFFAOYSA-N 0.000 description 1
- TZOHMAXCDNCYRH-UHFFFAOYSA-N CCOC(CC1=CC=C(CN(C(C=CC=C2)=C2N2)C2=O)C=C1)=O Chemical compound CCOC(CC1=CC=C(CN(C(C=CC=C2)=C2N2)C2=O)C=C1)=O TZOHMAXCDNCYRH-UHFFFAOYSA-N 0.000 description 1
- HWQBLOCYGMBOCW-UHFFFAOYSA-N CCOC(CC1=CC=C(CNC(C=CC=C2)=C2[N+]([O-])=O)C=C1)=O Chemical compound CCOC(CC1=CC=C(CNC(C=CC=C2)=C2[N+]([O-])=O)C=C1)=O HWQBLOCYGMBOCW-UHFFFAOYSA-N 0.000 description 1
- HOSXUIJWMGYTJV-UHFFFAOYSA-N CN(C(C=CC=C1)=C1N1CC2=CC(OC(F)(F)F)=CC=C2)C1=O Chemical compound CN(C(C=CC=C1)=C1N1CC2=CC(OC(F)(F)F)=CC=C2)C1=O HOSXUIJWMGYTJV-UHFFFAOYSA-N 0.000 description 1
- XYIIBZWOSNFDQN-UHFFFAOYSA-N CN(C)C(CC1=CC(CN(C(C=CC=C2)=C2N2)C2=O)=CC=C1)=O Chemical compound CN(C)C(CC1=CC(CN(C(C=CC=C2)=C2N2)C2=O)=CC=C1)=O XYIIBZWOSNFDQN-UHFFFAOYSA-N 0.000 description 1
- TVEIXYUQSUNLHO-UHFFFAOYSA-N CN(C)C(CC1=CC=C(CN(C(C=C(C=C2)F)=C2N2)C2=O)C=C1)=O Chemical compound CN(C)C(CC1=CC=C(CN(C(C=C(C=C2)F)=C2N2)C2=O)C=C1)=O TVEIXYUQSUNLHO-UHFFFAOYSA-N 0.000 description 1
- NFBIKLVUODEBRY-UHFFFAOYSA-N CNC(CC1=CC=C(CN(C(C=CC=C2)=C2N2)C2=O)C=C1)=O Chemical compound CNC(CC1=CC=C(CN(C(C=CC=C2)=C2N2)C2=O)C=C1)=O NFBIKLVUODEBRY-UHFFFAOYSA-N 0.000 description 1
- HHYYZEAJAOBEQN-UHFFFAOYSA-N CNC(CC1=CC=C(CN(C2=CC(F)=CC=C2N2)C2=O)C=C1)=O Chemical compound CNC(CC1=CC=C(CN(C2=CC(F)=CC=C2N2)C2=O)C=C1)=O HHYYZEAJAOBEQN-UHFFFAOYSA-N 0.000 description 1
- YEMFHWXYHNNPAP-UHFFFAOYSA-N COC1(CC1)C(NCC1=CC=C(CN(C(C=CC=C2)=C2N2)C2=O)C=C1)=O Chemical compound COC1(CC1)C(NCC1=CC=C(CN(C(C=CC=C2)=C2N2)C2=O)C=C1)=O YEMFHWXYHNNPAP-UHFFFAOYSA-N 0.000 description 1
- UBWCNQTUCPHPHN-UHFFFAOYSA-N CS(NCC1=CC=C(CN(C(C=CC=C2)=C2N2C(F)F)C2=O)C=C1)(=O)=O Chemical compound CS(NCC1=CC=C(CN(C(C=CC=C2)=C2N2C(F)F)C2=O)C=C1)(=O)=O UBWCNQTUCPHPHN-UHFFFAOYSA-N 0.000 description 1
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 1
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 1
- 229940045513 CTLA4 antagonist Drugs 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- OQSZJLLDTFASRX-UHFFFAOYSA-N ClC1=C(CC2=NN=CO2)C=CC(Br)=C1 Chemical compound ClC1=C(CC2=NN=CO2)C=CC(Br)=C1 OQSZJLLDTFASRX-UHFFFAOYSA-N 0.000 description 1
- 241000202285 Claravis Species 0.000 description 1
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 238000006969 Curtius rearrangement reaction Methods 0.000 description 1
- 102100021906 Cyclin-O Human genes 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- WEAHRLBPCANXCN-UHFFFAOYSA-N Daunomycin Natural products CCC1(O)CC(OC2CC(N)C(O)C(C)O2)c3cc4C(=O)c5c(OC)cccc5C(=O)c4c(O)c3C1 WEAHRLBPCANXCN-UHFFFAOYSA-N 0.000 description 1
- GUGHGUXZJWAIAS-QQYBVWGSSA-N Daunorubicin hydrochloride Chemical compound Cl.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 GUGHGUXZJWAIAS-QQYBVWGSSA-N 0.000 description 1
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-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
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 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
- LMHIPJMTZHDKEW-XQYLJSSYSA-M Epoprostenol sodium Chemical compound [Na+].O1\C(=C/CCCC([O-])=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 LMHIPJMTZHDKEW-XQYLJSSYSA-M 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 101000834898 Homo sapiens Alpha-synuclein Proteins 0.000 description 1
- 101100407305 Homo sapiens CD274 gene Proteins 0.000 description 1
- 101000897441 Homo sapiens Cyclin-O Proteins 0.000 description 1
- 101100407307 Homo sapiens PDCD1LG2 gene Proteins 0.000 description 1
- 101000652359 Homo sapiens Spermatogenesis-associated protein 2 Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 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
- 102000037982 Immune checkpoint proteins Human genes 0.000 description 1
- 108091008036 Immune checkpoint proteins Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- 150000008575 L-amino acids Chemical class 0.000 description 1
- 101710169152 L-amino oxidase Proteins 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 125000002435 L-phenylalanyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000003798 L-tyrosyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C([H])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 description 1
- 102000017578 LAG3 Human genes 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 101150030213 Lag3 gene Proteins 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 208000002030 Merkel cell carcinoma Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 description 1
- 108091092878 Microsatellite Proteins 0.000 description 1
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 1
- UCHDWCPVSPXUMX-TZIWLTJVSA-N Montelukast Chemical compound CC(C)(O)C1=CC=CC=C1CC[C@H](C=1C=C(\C=C\C=2N=C3C=C(Cl)C=CC3=CC=2)C=CC=1)SCC1(CC(O)=O)CC1 UCHDWCPVSPXUMX-TZIWLTJVSA-N 0.000 description 1
- AIHCBZPZRSGYHL-UHFFFAOYSA-N N#CC1=CC=CC(NC(CC2=CC(CN(C(C=CC=C3)=C3N3)C3=O)=CC=C2)=O)=C1 Chemical compound N#CC1=CC=CC(NC(CC2=CC(CN(C(C=CC=C3)=C3N3)C3=O)=CC=C2)=O)=C1 AIHCBZPZRSGYHL-UHFFFAOYSA-N 0.000 description 1
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
- ZRKWMRDKSOPRRS-UHFFFAOYSA-N N-Methyl-N-nitrosourea Chemical compound O=NN(C)C(N)=O ZRKWMRDKSOPRRS-UHFFFAOYSA-N 0.000 description 1
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
- OHLUUHNLEMFGTQ-UHFFFAOYSA-N N-methylacetamide Chemical compound CNC(C)=O OHLUUHNLEMFGTQ-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- GZVLUHJIXIEGOZ-UHFFFAOYSA-N NC(C(NCC1=CC=CC=C1)=CC=C1)=C1N1CCCC1 Chemical compound NC(C(NCC1=CC=CC=C1)=CC=C1)=C1N1CCCC1 GZVLUHJIXIEGOZ-UHFFFAOYSA-N 0.000 description 1
- RJKJVKVGQYHWAR-UHFFFAOYSA-N NC1=CC(Cl)=CC=C1NCC1=CC=C(CC2=NN=CO2)C=C1 Chemical compound NC1=CC(Cl)=CC=C1NCC1=CC=C(CC2=NN=CO2)C=C1 RJKJVKVGQYHWAR-UHFFFAOYSA-N 0.000 description 1
- NSMMPRFZRDTHJO-UHFFFAOYSA-N NCC(SC(Br)=C1)=C1Cl Chemical compound NCC(SC(Br)=C1)=C1Cl NSMMPRFZRDTHJO-UHFFFAOYSA-N 0.000 description 1
- UMSWNEAFJBOMBB-UHFFFAOYSA-N NNC(=O)Cc1ccc(Br)cc1Cl Chemical compound NNC(=O)Cc1ccc(Br)cc1Cl UMSWNEAFJBOMBB-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 206010029266 Neuroendocrine carcinoma of the skin Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- VIJFJBXEWLMQRQ-KRXBUXKQSA-N O/N=C/C(SC(Br)=C1)=C1Cl Chemical compound O/N=C/C(SC(Br)=C1)=C1Cl VIJFJBXEWLMQRQ-KRXBUXKQSA-N 0.000 description 1
- XAUGZNJRYZPZBP-UHFFFAOYSA-N O=C(C1=CC(CN(C(C=CC=C2)=C2N2)C2=O)=CC=C1)N1CCC1 Chemical compound O=C(C1=CC(CN(C(C=CC=C2)=C2N2)C2=O)=CC=C1)N1CCC1 XAUGZNJRYZPZBP-UHFFFAOYSA-N 0.000 description 1
- WNHGABRILCULDB-UHFFFAOYSA-N O=C(C1=CC(CN(C(C=CC=C2)=C2N2)C2=O)=CC=C1)NCC(F)(F)F Chemical compound O=C(C1=CC(CN(C(C=CC=C2)=C2N2)C2=O)=CC=C1)NCC(F)(F)F WNHGABRILCULDB-UHFFFAOYSA-N 0.000 description 1
- BQYAVIPPRBLNEH-UHFFFAOYSA-N O=C(CC1=CC(CN(C(C=CC=C2)=C2N2)C2=O)=CC=C1)NC1=CC=CN=C1 Chemical compound O=C(CC1=CC(CN(C(C=CC=C2)=C2N2)C2=O)=CC=C1)NC1=CC=CN=C1 BQYAVIPPRBLNEH-UHFFFAOYSA-N 0.000 description 1
- ZEFDCDHXMHYANQ-UHFFFAOYSA-N O=C(CC1=CC=C(CN(C(C=CC=C2)=C2N2)C2=O)C=C1)NC(CC1)CC1F Chemical compound O=C(CC1=CC=C(CN(C(C=CC=C2)=C2N2)C2=O)C=C1)NC(CC1)CC1F ZEFDCDHXMHYANQ-UHFFFAOYSA-N 0.000 description 1
- UKZWQIAGYBCEMR-UHFFFAOYSA-N O=C1N(C(F)F)C(C=CC=C2)=C2N1CC1=CC=CC=C1 Chemical compound O=C1N(C(F)F)C(C=CC=C2)=C2N1CC1=CC=CC=C1 UKZWQIAGYBCEMR-UHFFFAOYSA-N 0.000 description 1
- DZBIQFIYIACXJJ-UHFFFAOYSA-N O=C1N(CC(C=CC(CN(C(C=CC=C2)=C2N2)C2=O)=C2)=C2I)CCC1 Chemical compound O=C1N(CC(C=CC(CN(C(C=CC=C2)=C2N2)C2=O)=C2)=C2I)CCC1 DZBIQFIYIACXJJ-UHFFFAOYSA-N 0.000 description 1
- LTYOVPZCMPZYBT-UHFFFAOYSA-N O=C1N(CC(C=CC(CN(C2=CC=CC=C2N2)C2=O)=C2)=C2Cl)CCC1 Chemical compound O=C1N(CC(C=CC(CN(C2=CC=CC=C2N2)C2=O)=C2)=C2Cl)CCC1 LTYOVPZCMPZYBT-UHFFFAOYSA-N 0.000 description 1
- JIWRHWBAFJLBAZ-UHFFFAOYSA-N O=C1N(CC(C=CC(CN2C(Cl)=NC3=C2C=CC=C3)=C2)=C2I)CCC1 Chemical compound O=C1N(CC(C=CC(CN2C(Cl)=NC3=C2C=CC=C3)=C2)=C2I)CCC1 JIWRHWBAFJLBAZ-UHFFFAOYSA-N 0.000 description 1
- TXCZDRNPLYUERB-UHFFFAOYSA-N O=C1N(CC(SC(Br)=C2)=C2Cl)CCC1 Chemical compound O=C1N(CC(SC(Br)=C2)=C2Cl)CCC1 TXCZDRNPLYUERB-UHFFFAOYSA-N 0.000 description 1
- BLXOCIQRLTXYTC-UHFFFAOYSA-N O=C1N(CC2=CC(C3=NN=CO3)=CC=C2)C2=CC=CC=C2N1 Chemical compound O=C1N(CC2=CC(C3=NN=CO3)=CC=C2)C2=CC=CC=C2N1 BLXOCIQRLTXYTC-UHFFFAOYSA-N 0.000 description 1
- XFDUKCYNJMKAQW-UHFFFAOYSA-N O=C1N(CC2=CC(CCC3)=C3C=C2)C(C=CC=C2)=C2N1 Chemical compound O=C1N(CC2=CC(CCC3)=C3C=C2)C(C=CC=C2)=C2N1 XFDUKCYNJMKAQW-UHFFFAOYSA-N 0.000 description 1
- XULUKDXOXIIAEJ-UHFFFAOYSA-N O=C1N(CC2=CC(I)=C(CBr)C=C2)CCC1 Chemical compound O=C1N(CC2=CC(I)=C(CBr)C=C2)CCC1 XULUKDXOXIIAEJ-UHFFFAOYSA-N 0.000 description 1
- NJGOWZURKAMURR-UHFFFAOYSA-N O=C1N(CC2=CC=C(CN(C(C=CC(F)=C3)=C3N3)C3=O)C=C2)CCC1 Chemical compound O=C1N(CC2=CC=C(CN(C(C=CC(F)=C3)=C3N3)C3=O)C=C2)CCC1 NJGOWZURKAMURR-UHFFFAOYSA-N 0.000 description 1
- GXEKOPATTPUDJT-UHFFFAOYSA-N O=C1N(CC2=CC=C(CN(C3=CC=CC=C3N3)C3=O)C=N2)CCC1 Chemical compound O=C1N(CC2=CC=C(CN(C3=CC=CC=C3N3)C3=O)C=N2)CCC1 GXEKOPATTPUDJT-UHFFFAOYSA-N 0.000 description 1
- GAUXBGPUUNBLCB-UHFFFAOYSA-N O=C1N(CC2=CC=C(CN(CCOC3)S3(=O)=O)C=C2)C(C=CC=C2)=C2N1 Chemical compound O=C1N(CC2=CC=C(CN(CCOC3)S3(=O)=O)C=C2)C(C=CC=C2)=C2N1 GAUXBGPUUNBLCB-UHFFFAOYSA-N 0.000 description 1
- NFXFNKHDALYTSU-UHFFFAOYSA-N O=C1N(CC2=CC=C(CN3C(Cl)=NC4=C3C=CC(F)=C4)C=C2)CCC1 Chemical compound O=C1N(CC2=CC=C(CN3C(Cl)=NC4=C3C=CC(F)=C4)C=C2)CCC1 NFXFNKHDALYTSU-UHFFFAOYSA-N 0.000 description 1
- YCKXBNFVRWLTEC-UHFFFAOYSA-N O=C1N(CC2=CC=CC=C2)C(C=CC=C2N3CCCC3)=C2N1 Chemical compound O=C1N(CC2=CC=CC=C2)C(C=CC=C2N3CCCC3)=C2N1 YCKXBNFVRWLTEC-UHFFFAOYSA-N 0.000 description 1
- ZLIBCORXEMUTFZ-UHFFFAOYSA-N O=C1N(CCCCC2=C3N=CC=CC3=CC=C2)C(C=CC=C2)=C2N1 Chemical compound O=C1N(CCCCC2=C3N=CC=CC3=CC=C2)C(C=CC=C2)=C2N1 ZLIBCORXEMUTFZ-UHFFFAOYSA-N 0.000 description 1
- YBEXQKJALTXVGZ-UHFFFAOYSA-N O=C1N(CCCOC2=C3N=CC=CC3=CC=C2)C(C=CC=C2)=C2N1 Chemical compound O=C1N(CCCOC2=C3N=CC=CC3=CC=C2)C(C=CC=C2)=C2N1 YBEXQKJALTXVGZ-UHFFFAOYSA-N 0.000 description 1
- UPELYOZTRRKFPT-UHFFFAOYSA-N OC(CC1=CC=C(CN(C(C=C(C=C2)F)=C2N2)C2=O)C=C1)=O Chemical compound OC(CC1=CC=C(CN(C(C=C(C=C2)F)=C2N2)C2=O)C=C1)=O UPELYOZTRRKFPT-UHFFFAOYSA-N 0.000 description 1
- RAVOXFFDDZXPCF-UHFFFAOYSA-N OC(CC1=CC=C(CN(C(C=CC=C2)=C2N2)C2=O)C=C1)=O Chemical compound OC(CC1=CC=C(CN(C(C=CC=C2)=C2N2)C2=O)C=C1)=O RAVOXFFDDZXPCF-UHFFFAOYSA-N 0.000 description 1
- BBDACSUDLCNPJO-UHFFFAOYSA-N OCc1ccc(CO)c(I)c1 Chemical compound OCc1ccc(CO)c(I)c1 BBDACSUDLCNPJO-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- VQDBNKDJNJQRDG-UHFFFAOYSA-N Pirbuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=N1 VQDBNKDJNJQRDG-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
- 101710094000 Programmed cell death 1 ligand 1 Proteins 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
- GIIZNNXWQWCKIB-UHFFFAOYSA-N Serevent Chemical compound C1=C(O)C(CO)=CC(C(O)CNCCCCCCOCCCCC=2C=CC=CC=2)=C1 GIIZNNXWQWCKIB-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 229920002253 Tannate Polymers 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 description 1
- SECKRCOLJRRGGV-UHFFFAOYSA-N Vardenafil Chemical compound CCCC1=NC(C)=C(C(N=2)=O)N1NC=2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(CC)CC1 SECKRCOLJRRGGV-UHFFFAOYSA-N 0.000 description 1
- 238000007239 Wittig reaction Methods 0.000 description 1
- YEEZWCHGZNKEEK-UHFFFAOYSA-N Zafirlukast Chemical compound COC1=CC(C(=O)NS(=O)(=O)C=2C(=CC=CC=2)C)=CC=C1CC(C1=C2)=CN(C)C1=CC=C2NC(=O)OC1CCCC1 YEEZWCHGZNKEEK-UHFFFAOYSA-N 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- XRGSSROOYSFMMS-UHFFFAOYSA-N [3-(trifluoromethoxy)phenyl]methanol Chemical compound OCC1=CC=CC(OC(F)(F)F)=C1 XRGSSROOYSFMMS-UHFFFAOYSA-N 0.000 description 1
- DFMCYRPZULCNFN-UHFFFAOYSA-N [4-(1,3,4-oxadiazol-2-ylmethyl)phenyl]methanamine Chemical compound C1=CC(CN)=CC=C1CC1=NN=CO1 DFMCYRPZULCNFN-UHFFFAOYSA-N 0.000 description 1
- URTFMMGCFCAFDU-UHFFFAOYSA-N [NH3+]CC1=CC=C(CN(C(C=CC=C2)=C2N2C(F)F)C2=O)C=C1.[Cl-] Chemical compound [NH3+]CC1=CC=C(CN(C(C=CC=C2)=C2N2C(F)F)C2=O)C=C1.[Cl-] URTFMMGCFCAFDU-UHFFFAOYSA-N 0.000 description 1
- RDXARWSSOJYNLI-UHFFFAOYSA-N [P].[K] Chemical compound [P].[K] RDXARWSSOJYNLI-UHFFFAOYSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical compound ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 229940064305 adrucil Drugs 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- QNAYBMKLOCPYGJ-UHFFFAOYSA-M alaninate Chemical compound CC(N)C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-M 0.000 description 1
- NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 description 1
- 229940110282 alimta Drugs 0.000 description 1
- 229960001445 alitretinoin Drugs 0.000 description 1
- 229940098174 alkeran Drugs 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 229960000711 alprostadil Drugs 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- OUJTZYPIHDYQMC-LJQANCHMSA-N ambrisentan Chemical compound O([C@@H](C(OC)(C=1C=CC=CC=1)C=1C=CC=CC=1)C(O)=O)C1=NC(C)=CC(C)=N1 OUJTZYPIHDYQMC-LJQANCHMSA-N 0.000 description 1
- 229960002414 ambrisentan Drugs 0.000 description 1
- HTIQEAQVCYTUBX-UHFFFAOYSA-N amlodipine Chemical compound CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl HTIQEAQVCYTUBX-UHFFFAOYSA-N 0.000 description 1
- 229960000528 amlodipine Drugs 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 229940022824 amnesteem Drugs 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 229940125708 antidiabetic agent Drugs 0.000 description 1
- 229960005475 antiinfective agent Drugs 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 239000003972 antineoplastic antibiotic Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 229960005370 atorvastatin Drugs 0.000 description 1
- 229940120638 avastin Drugs 0.000 description 1
- 229960003005 axitinib Drugs 0.000 description 1
- 229960002756 azacitidine Drugs 0.000 description 1
- OISFUZRUIGGTSD-LJTMIZJLSA-N azane;(2r,3r,4r,5s)-6-(methylamino)hexane-1,2,3,4,5-pentol Chemical class N.CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO OISFUZRUIGGTSD-LJTMIZJLSA-N 0.000 description 1
- 229910000063 azene Inorganic materials 0.000 description 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- 229940092705 beclomethasone Drugs 0.000 description 1
- NBMKJKDGKREAPL-DVTGEIKXSA-N beclomethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O NBMKJKDGKREAPL-DVTGEIKXSA-N 0.000 description 1
- 229960002707 bendamustine Drugs 0.000 description 1
- YTKUWDBFDASYHO-UHFFFAOYSA-N bendamustine Chemical compound ClCCN(CCCl)C1=CC=C2N(C)C(CCCC(O)=O)=NC2=C1 YTKUWDBFDASYHO-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- FCDPQMAOJARMTG-UHFFFAOYSA-L benzylidene-[1,3-bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene]-dichlororuthenium;tricyclohexylphosphane Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1.CC1=CC(C)=CC(C)=C1N(CCN1C=2C(=CC(C)=CC=2C)C)C1=[Ru](Cl)(Cl)=CC1=CC=CC=C1 FCDPQMAOJARMTG-UHFFFAOYSA-L 0.000 description 1
- RJNJWHFSKNJCTB-UHFFFAOYSA-N benzylurea Chemical compound NC(=O)NCC1=CC=CC=C1 RJNJWHFSKNJCTB-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- 229960000397 bevacizumab Drugs 0.000 description 1
- 229960002938 bexarotene Drugs 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 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
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- 229960003065 bosentan Drugs 0.000 description 1
- SXTRWVVIEPWAKM-UHFFFAOYSA-N bosentan hydrate Chemical compound O.COC1=CC=CC=C1OC(C(=NC(=N1)C=2N=CC=CN=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 SXTRWVVIEPWAKM-UHFFFAOYSA-N 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 229960004436 budesonide Drugs 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229960002092 busulfan Drugs 0.000 description 1
- 229940112133 busulfex Drugs 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 229940022399 cancer vaccine Drugs 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 229960004630 chlorambucil Drugs 0.000 description 1
- AHWRJPOOFGXEKF-UHFFFAOYSA-M chlororuthenium(1+);1,2,3,4,5-pentamethylcyclopenta-1,3-diene;triphenylphosphane Chemical compound [Ru+]Cl.CC=1C(C)=C(C)[C-](C)C=1C.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 AHWRJPOOFGXEKF-UHFFFAOYSA-M 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 229940031301 claravis Drugs 0.000 description 1
- 229940060799 clarus Drugs 0.000 description 1
- 229940090805 clavulanate Drugs 0.000 description 1
- HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 1
- GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 description 1
- 229960003009 clopidogrel Drugs 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- BJSUYFBLYBJBLT-UHFFFAOYSA-L copper(1+) tetrabutylazanium diiodide Chemical compound [Cu+].[I-].[I-].CCCC[N+](CCCC)(CCCC)CCCC BJSUYFBLYBJBLT-UHFFFAOYSA-L 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 229940088547 cosmegen Drugs 0.000 description 1
- 229960000265 cromoglicic acid Drugs 0.000 description 1
- 208000017763 cutaneous neuroendocrine carcinoma Diseases 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 150000001924 cycloalkanes Chemical class 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 238000005888 cyclopropanation reaction Methods 0.000 description 1
- PFWWSGFPICCWGU-UHFFFAOYSA-N cyclopropanesulfonyl chloride Chemical compound ClS(=O)(=O)C1CC1 PFWWSGFPICCWGU-UHFFFAOYSA-N 0.000 description 1
- 229960003901 dacarbazine Drugs 0.000 description 1
- 229940059359 dacogen Drugs 0.000 description 1
- 229960003334 daunorubicin citrate Drugs 0.000 description 1
- 229940107841 daunoxome Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 229940070968 depocyt Drugs 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- JAUGGEIKQIHSMF-UHFFFAOYSA-N dialuminum;dimagnesium;dioxido(oxo)silane;oxygen(2-);hydrate Chemical compound O.[O-2].[O-2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O.[O-][Si]([O-])=O JAUGGEIKQIHSMF-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 1
- 229960004166 diltiazem Drugs 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- SPCNPOWOBZQWJK-UHFFFAOYSA-N dimethoxy-(2-propan-2-ylsulfanylethylsulfanyl)-sulfanylidene-$l^{5}-phosphane Chemical compound COP(=S)(OC)SCCSC(C)C SPCNPOWOBZQWJK-UHFFFAOYSA-N 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical class [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- VLARUOGDXDTHEH-UHFFFAOYSA-L disodium cromoglycate Chemical compound [Na+].[Na+].O1C(C([O-])=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C([O-])=O)O2 VLARUOGDXDTHEH-UHFFFAOYSA-L 0.000 description 1
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- JRBPAEWTRLWTQC-UHFFFAOYSA-N dodecylamine Chemical compound CCCCCCCCCCCCN JRBPAEWTRLWTQC-UHFFFAOYSA-N 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 229940075117 droxia Drugs 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 229940009662 edetate Drugs 0.000 description 1
- 229940087477 ellence Drugs 0.000 description 1
- 230000002357 endometrial effect Effects 0.000 description 1
- 208000023965 endometrium neoplasm Diseases 0.000 description 1
- 150000002085 enols Chemical group 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- 229960001904 epirubicin Drugs 0.000 description 1
- 229960001123 epoprostenol Drugs 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- ZFDCWHPNBWPPHG-UHFFFAOYSA-N ethyl 2-(4-bromophenyl)acetate Chemical compound CCOC(=O)CC1=CC=C(Br)C=C1 ZFDCWHPNBWPPHG-UHFFFAOYSA-N 0.000 description 1
- FMELKQUZTWEFLT-UHFFFAOYSA-N ethyl 2-[4-(aminomethyl)phenyl]acetate Chemical compound CCOC(=O)CC1=CC=C(CN)C=C1 FMELKQUZTWEFLT-UHFFFAOYSA-N 0.000 description 1
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 1
- 229960002297 fenofibrate Drugs 0.000 description 1
- 229960000961 floxuridine Drugs 0.000 description 1
- 229960000390 fludarabine Drugs 0.000 description 1
- 229960005304 fludarabine phosphate Drugs 0.000 description 1
- 229960000676 flunisolide Drugs 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 229960002714 fluticasone Drugs 0.000 description 1
- MGNNYOODZCAHBA-GQKYHHCASA-N fluticasone Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(O)[C@@]2(C)C[C@@H]1O MGNNYOODZCAHBA-GQKYHHCASA-N 0.000 description 1
- 229960003765 fluvastatin Drugs 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 229960002848 formoterol Drugs 0.000 description 1
- BPZSYCZIITTYBL-UHFFFAOYSA-N formoterol Chemical compound C1=CC(OC)=CC=C1CC(C)NCC(O)C1=CC=C(O)C(NC=O)=C1 BPZSYCZIITTYBL-UHFFFAOYSA-N 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
- 229940125695 gastrointestinal agent Drugs 0.000 description 1
- 239000004083 gastrointestinal agent Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229960003627 gemfibrozil Drugs 0.000 description 1
- 229960001731 gluceptate Drugs 0.000 description 1
- KWMLJOLKUYYJFJ-VFUOTHLCSA-N glucoheptonic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)C(O)=O KWMLJOLKUYYJFJ-VFUOTHLCSA-N 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 229940049906 glutamate Drugs 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 102000035122 glycosylated proteins Human genes 0.000 description 1
- 108091005608 glycosylated proteins Proteins 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000002962 histologic effect Effects 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 229940096120 hydrea Drugs 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 229960001330 hydroxycarbamide Drugs 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 229960000908 idarubicin Drugs 0.000 description 1
- 229940090411 ifex Drugs 0.000 description 1
- 229960001101 ifosfamide Drugs 0.000 description 1
- 229960002240 iloprost Drugs 0.000 description 1
- HIFJCPQKFCZDDL-ACWOEMLNSA-N iloprost Chemical compound C1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)C(C)CC#CC)[C@H](O)C[C@@H]21 HIFJCPQKFCZDDL-ACWOEMLNSA-N 0.000 description 1
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 1
- 230000003832 immune regulation Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000037451 immune surveillance Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 229960001888 ipratropium Drugs 0.000 description 1
- OEXHQOGQTVQTAT-JRNQLAHRSA-N ipratropium Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 OEXHQOGQTVQTAT-JRNQLAHRSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 229940001447 lactate Drugs 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 229940063725 leukeran Drugs 0.000 description 1
- 229950008204 levosalbutamol Drugs 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 229960002247 lomustine Drugs 0.000 description 1
- 229960004844 lovastatin Drugs 0.000 description 1
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 1
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
- 201000005243 lung squamous cell carcinoma Diseases 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 229940049920 malate Drugs 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
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 201000010893 malignant breast melanoma Diseases 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 229940087732 matulane Drugs 0.000 description 1
- QZIQJVCYUQZDIR-UHFFFAOYSA-N mechlorethamine hydrochloride Chemical compound Cl.ClCCN(C)CCCl QZIQJVCYUQZDIR-UHFFFAOYSA-N 0.000 description 1
- 229960002868 mechlorethamine hydrochloride Drugs 0.000 description 1
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 1
- IZDROVVXIHRYMH-UHFFFAOYSA-N methanesulfonic anhydride Chemical compound CS(=O)(=O)OS(C)(=O)=O IZDROVVXIHRYMH-UHFFFAOYSA-N 0.000 description 1
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- FQVAIXVMXMXFKD-UHFFFAOYSA-N methyl 2-(4-bromo-2-methylphenyl)acetate Chemical compound COC(=O)CC1=CC=C(Br)C=C1C FQVAIXVMXMXFKD-UHFFFAOYSA-N 0.000 description 1
- LLDQUDYCTIKKFV-UHFFFAOYSA-N methyl 2-[4-(hydroxymethyl)phenyl]acetate Chemical compound COC(=O)CC1=CC=C(CO)C=C1 LLDQUDYCTIKKFV-UHFFFAOYSA-N 0.000 description 1
- YUHSMQQNPRLEEJ-UHFFFAOYSA-N methyl 3-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=CC(CBr)=C1 YUHSMQQNPRLEEJ-UHFFFAOYSA-N 0.000 description 1
- NLWBJPPMPLPZIE-UHFFFAOYSA-N methyl 4-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=C(CBr)C=C1 NLWBJPPMPLPZIE-UHFFFAOYSA-N 0.000 description 1
- OKGJNDJQJVCPKL-UHFFFAOYSA-N methyl N-(2-bromo-6-fluorophenyl)carbamate Chemical compound COC(=O)Nc1c(F)cccc1Br OKGJNDJQJVCPKL-UHFFFAOYSA-N 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- MOLHKSHRWIRTMV-UHFFFAOYSA-N methyl n-(2-bromo-4-chlorophenyl)carbamate Chemical compound COC(=O)NC1=CC=C(Cl)C=C1Br MOLHKSHRWIRTMV-UHFFFAOYSA-N 0.000 description 1
- DIMRCPQVSZQRSC-UHFFFAOYSA-N methyl n-(2-bromo-4-methylphenyl)carbamate Chemical compound COC(=O)NC1=CC=C(C)C=C1Br DIMRCPQVSZQRSC-UHFFFAOYSA-N 0.000 description 1
- LRMHVVPPGGOAJQ-UHFFFAOYSA-N methyl nitrate Chemical compound CO[N+]([O-])=O LRMHVVPPGGOAJQ-UHFFFAOYSA-N 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 229960004584 methylprednisolone Drugs 0.000 description 1
- 239000004200 microcrystalline wax Substances 0.000 description 1
- 235000019808 microcrystalline wax Nutrition 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229960001664 mometasone Drugs 0.000 description 1
- QLIIKPVHVRXHRI-CXSFZGCWSA-N mometasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CCl)(O)[C@@]1(C)C[C@@H]2O QLIIKPVHVRXHRI-CXSFZGCWSA-N 0.000 description 1
- 229960005127 montelukast Drugs 0.000 description 1
- 229950003968 motesanib Drugs 0.000 description 1
- 210000000066 myeloid cell Anatomy 0.000 description 1
- 229940090009 myleran Drugs 0.000 description 1
- ACTNHJDHMQSOGL-UHFFFAOYSA-N n',n'-dibenzylethane-1,2-diamine Chemical compound C=1C=CC=CC=1CN(CCN)CC1=CC=CC=C1 ACTNHJDHMQSOGL-UHFFFAOYSA-N 0.000 description 1
- HBBBWKUVJSIFKV-UHFFFAOYSA-N n-[(4-bromophenyl)methyl]acetamide Chemical compound CC(=O)NCC1=CC=C(Br)C=C1 HBBBWKUVJSIFKV-UHFFFAOYSA-N 0.000 description 1
- OYQXEMVZGHIXBJ-UHFFFAOYSA-N n-[(4-bromophenyl)methyl]methanesulfonamide Chemical compound CS(=O)(=O)NCC1=CC=C(Br)C=C1 OYQXEMVZGHIXBJ-UHFFFAOYSA-N 0.000 description 1
- 125000006606 n-butoxy group Chemical group 0.000 description 1
- XBXCNNQPRYLIDE-UHFFFAOYSA-M n-tert-butylcarbamate Chemical compound CC(C)(C)NC([O-])=O XBXCNNQPRYLIDE-UHFFFAOYSA-M 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 229940080607 nexavar Drugs 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
- 229960001597 nifedipine Drugs 0.000 description 1
- 229940109551 nipent Drugs 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 229960000470 omalizumab Drugs 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 238000007833 oxidative deamination reaction Methods 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- 150000002942 palmitic acid derivatives Chemical class 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 229940096763 panretin Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- VMZMNAABQBOLAK-DBILLSOUSA-N pasireotide Chemical compound C([C@H]1C(=O)N2C[C@@H](C[C@H]2C(=O)N[C@H](C(=O)N[C@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@H](C(N[C@@H](CC=2C=CC(OCC=3C=CC=CC=3)=CC=2)C(=O)N1)=O)CCCCN)C=1C=CC=CC=1)OC(=O)NCCN)C1=CC=CC=C1 VMZMNAABQBOLAK-DBILLSOUSA-N 0.000 description 1
- 229960005415 pasireotide Drugs 0.000 description 1
- 108700017947 pasireotide Proteins 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229960005079 pemetrexed Drugs 0.000 description 1
- 229960002340 pentostatin Drugs 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229960005414 pirbuterol Drugs 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229960002965 pravastatin Drugs 0.000 description 1
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 229960000624 procarbazine Drugs 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 1
- KPBSJEBFALFJTO-UHFFFAOYSA-N propane-1-sulfonyl chloride Chemical compound CCCS(Cl)(=O)=O KPBSJEBFALFJTO-UHFFFAOYSA-N 0.000 description 1
- GMVPRGQOIOIIMI-DWKJAMRDSA-N prostaglandin E1 Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(O)=O GMVPRGQOIOIIMI-DWKJAMRDSA-N 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 229940117820 purinethol Drugs 0.000 description 1
- HDOUGSFASVGDCS-UHFFFAOYSA-N pyridin-3-ylmethanamine Chemical compound NCC1=CC=CN=C1 HDOUGSFASVGDCS-UHFFFAOYSA-N 0.000 description 1
- GMHCEDDZKAYPLB-UHFFFAOYSA-N pyridine-2-carboximidamide;hydrochloride Chemical compound [Cl-].NC(=[NH2+])C1=CC=CC=N1 GMHCEDDZKAYPLB-UHFFFAOYSA-N 0.000 description 1
- 150000004040 pyrrolidinones Chemical class 0.000 description 1
- MIXMJCQRHVAJIO-TZHJZOAOSA-N qk4dys664x Chemical compound O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O MIXMJCQRHVAJIO-TZHJZOAOSA-N 0.000 description 1
- MCJGNVYPOGVAJF-UHFFFAOYSA-N quinolin-8-ol Chemical compound C1=CN=C2C(O)=CC=CC2=C1 MCJGNVYPOGVAJF-UHFFFAOYSA-N 0.000 description 1
- OVZQVGZERAFSPI-UHFFFAOYSA-N quinoline-8-carbaldehyde Chemical compound C1=CN=C2C(C=O)=CC=CC2=C1 OVZQVGZERAFSPI-UHFFFAOYSA-N 0.000 description 1
- 238000006578 reductive coupling reaction Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229930002330 retinoic acid Natural products 0.000 description 1
- 229940061969 rheumatrex Drugs 0.000 description 1
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 description 1
- 229960000672 rosuvastatin Drugs 0.000 description 1
- 229960002052 salbutamol Drugs 0.000 description 1
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 229960004017 salmeterol Drugs 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 201000004409 schistosomiasis Diseases 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 229960003310 sildenafil Drugs 0.000 description 1
- 229960002855 simvastatin Drugs 0.000 description 1
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000003998 snake venom Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical class [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical class [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 229960003787 sorafenib Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229940034345 sotret Drugs 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 229960001052 streptozocin Drugs 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000003890 succinate salts Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000034223 susceptibility to 2 systemic lupus erythematosus Diseases 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 229960000835 tadalafil Drugs 0.000 description 1
- IEHKWSGCTWLXFU-IIBYNOLFSA-N tadalafil Chemical compound C1=C2OCOC2=CC([C@@H]2C3=C([C]4C=CC=CC4=N3)C[C@H]3N2C(=O)CN(C3=O)C)=C1 IEHKWSGCTWLXFU-IIBYNOLFSA-N 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940099419 targretin Drugs 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 229940066453 tecentriq Drugs 0.000 description 1
- 229940061353 temodar Drugs 0.000 description 1
- 229960001278 teniposide Drugs 0.000 description 1
- OVIMTIMRQGWSOG-UHFFFAOYSA-N tert-butyl 2-[3-(aminomethyl)phenyl]acetate Chemical compound CC(C)(C)OC(=O)CC1=CC=CC(CN)=C1 OVIMTIMRQGWSOG-UHFFFAOYSA-N 0.000 description 1
- XXEUULGDNGDBMS-UHFFFAOYSA-N tert-butyl 2-[4-(aminomethyl)phenyl]acetate Chemical compound CC(C)(C)OC(=O)CC1=CC=C(CN)C=C1 XXEUULGDNGDBMS-UHFFFAOYSA-N 0.000 description 1
- YGJXBTRLYHCWGD-UHFFFAOYSA-N tert-butyl 4-(bromomethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CBr)CC1 YGJXBTRLYHCWGD-UHFFFAOYSA-N 0.000 description 1
- UOCVSZYBRMGQOL-UHFFFAOYSA-N tert-butyl 5-bromo-2,3-dihydroindole-1-carboxylate Chemical compound BrC1=CC=C2N(C(=O)OC(C)(C)C)CCC2=C1 UOCVSZYBRMGQOL-UHFFFAOYSA-N 0.000 description 1
- CRAQTQCTGGCBBK-UHFFFAOYSA-N tert-butyl 6-chloro-2-oxo-3h-benzimidazole-1-carboxylate Chemical compound ClC1=CC=C2NC(=O)N(C(=O)OC(C)(C)C)C2=C1 CRAQTQCTGGCBBK-UHFFFAOYSA-N 0.000 description 1
- YZEZLDIZHPBHGQ-UHFFFAOYSA-N tert-butyl n-(6-bromo-2,3-dihydro-1h-inden-1-yl)carbamate Chemical compound C1=C(Br)C=C2C(NC(=O)OC(C)(C)C)CCC2=C1 YZEZLDIZHPBHGQ-UHFFFAOYSA-N 0.000 description 1
- QKSQWQOAUQFORH-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonylimino]carbamate Chemical compound CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C QKSQWQOAUQFORH-UHFFFAOYSA-N 0.000 description 1
- UYGBIHFTZHBDEQ-UHFFFAOYSA-N tert-butyl n-[[4-(bromomethyl)phenyl]methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1=CC=C(CBr)C=C1 UYGBIHFTZHBDEQ-UHFFFAOYSA-N 0.000 description 1
- KBVGWJGZRWDFED-UHFFFAOYSA-N tert-butyl n-[[4-[(2-aminoanilino)methyl]phenyl]methyl]carbamate Chemical compound C1=CC(CNC(=O)OC(C)(C)C)=CC=C1CNC1=CC=CC=C1N KBVGWJGZRWDFED-UHFFFAOYSA-N 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- 229960004559 theobromine Drugs 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- FKKJJPMGAWGYPN-UHFFFAOYSA-N thiophen-2-ylmethanamine Chemical compound NCC1=CC=CS1 FKKJJPMGAWGYPN-UHFFFAOYSA-N 0.000 description 1
- 229960001196 thiotepa Drugs 0.000 description 1
- 229960003087 tioguanine Drugs 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 238000000954 titration curve Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 229940035307 toposar Drugs 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 229940111528 trexall Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- PBIMIGNDTBRRPI-UHFFFAOYSA-N trifluoro borate Chemical compound FOB(OF)OF PBIMIGNDTBRRPI-UHFFFAOYSA-N 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- 208000022679 triple-negative breast carcinoma Diseases 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 229940038773 trisodium citrate Drugs 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-M valerate Chemical class CCCCC([O-])=O NQPDZGIKBAWPEJ-UHFFFAOYSA-M 0.000 description 1
- 229960002381 vardenafil Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229940065658 vidaza Drugs 0.000 description 1
- 229960005080 warfarin Drugs 0.000 description 1
- PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
- UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical group CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 1
- 229960004764 zafirlukast Drugs 0.000 description 1
- 229940053890 zanosar Drugs 0.000 description 1
- 229960005332 zileuton Drugs 0.000 description 1
- MWLSOWXNZPKENC-SSDOTTSWSA-N zileuton Chemical compound C1=CC=C2SC([C@H](N(O)C(N)=O)C)=CC2=C1 MWLSOWXNZPKENC-SSDOTTSWSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4188—1,3-Diazoles condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4192—1,2,3-Triazoles
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4196—1,2,4-Triazoles
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4245—Oxadiazoles
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further 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
- A61K31/435—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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
-
- 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further 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
- A61K31/495—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
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/34—Oxygen atoms in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D235/26—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/08—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing alicyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D419/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms
- C07D419/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D419/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
Xは、CH又はSであり、ここで、XがSである場合、Zは、CHであり;
Yは、CH又は結合であり;
Zは、CH又はSであり、ここで、ZがSである場合、Xは、CHであり;
Aは、アリール、C3-C10シクロアルキル、ヘテロアリール又はシクロヘテロアルキルであり;
Lは、直鎖又は分枝鎖の(C1-C5)アルキレニルであり、ここで、L中の1以上の-CH2-基は、O及びNHからなる群から選択される部分で独立して置き換えられてもよく;
R1の各存在は、ハロゲン、C1-C6アルキル又はシクロヘテロアルキルであり;
R2の各存在は、-C1-C6アルキルNR4COC3-C6シクロアルキル、-C1-C6アルキルNR4COC1-C6アルキル、-C1-C6アルキルCONR4C1-C6アルキル、ハロゲン、アルコキシ、-C1-C6アルキルシクロヘテロアルキル、-C1-C6アルキルCONR4アリール、C1-C6アルキル、-C1-C6アルキルCOシクロヘテロアルキル、-C1-C6アルキルCONR4ヘテロアリール、-C1-C6アルキルNR4SO2C1-C6アルキル、-C1-C6アルキルNR4SO2C3-C6シクロアルキル、C3-C6シクロアルキル、-C1-C6アルキルCONR4C3-C6シクロアルキル、シクロヘテロアルキル、ハロC1-C6アルキル、-CONR4ハロアルキル、-COシクロヘテロアルキル、CN、-CONR4C1-C6アルキル、-CONR4C3-C6シクロアルキル、ヘテロアリール、アリール、ハロアルコキシ、-C1-C6アルキルC3-C10シクロアルキル、オキソ、-C1-C6アルキルヘテロアリール、-NR4COC1-C6アルキルから独立して選択され、ここで、該-C1-C6アルキルNR4COC3-C6シクロアルキル、-C1-C6アルキルCONR4C3-C6シクロアルキル、-C1-C6アルキルCONR4アリール、-C1-C6アルキルシクロヘテロアルキル、-C1-C6アルキルCOシクロヘテロアルキル、C3-C6シクロアルキル、シクロヘテロアルキル、ヘテロアリール、-C1-C6アルキルC3-C10シクロアルキルは、置換されていないか又はアルコキシ、CN、-C1-C6アルキルOH、ハロゲン、C1-C6アルキル、ハロC1-C6アルキル、オキソ、OH、CN、-C1-C6アルキルCN、-COC1-C6アルキル及びC3-C6シクロアルキルからなる群から選択される1~3の置換基で置換されており;
R3は、水素、C1-C6アルキル又はハロC1-C6アルキルであり;
R4は、C1-C6アルキル又は水素であり;
mは、0、1又は2であり;及び、
nは、0、1、2又は3である〕
で表される化合物又はその薬学的に許容される塩である。
Aは、アリール、C3-C10シクロアルキル、ヘテロアリール又はシクロヘテロアルキルであり;
Lは、直鎖又は分枝鎖の(C1-C5)アルキレニルであり、ここで、L中の1以上の-CH2-基は、O及びNHからなる群から選択される部分で独立して置き換えられてもよく;
R1の各存在は、ハロゲン、C1-C6アルキル又はシクロヘテロアルキルから独立して選択され;
R2の各存在は、-C1-C6アルキルNR4COC3-C6シクロアルキル、-C1-C6アルキルNR4COC1-C6アルキル、-C1-C6アルキルCONR4C1-C6アルキル、ハロゲン、アルコキシ、-C1-C6アルキルシクロヘテロアルキル、-C1-C6アルキルCONR4アリール、C1-C6アルキル、-C1-C6アルキルCOシクロヘテロアルキル、-C1-C6アルキルCONR4ヘテロアリール、-C1-C6アルキルNR4SO2C1-C6アルキル、-C1-C6アルキルNR4SO2C3-C6シクロアルキル、C3-C6シクロアルキル、-C1-C6アルキルCONR4C3-C6シクロアルキル、シクロヘテロアルキル、ハロC1-C6アルキル、-CONR4ハロアルキル、-COシクロヘテロアルキル、CN、-CONR4C1-C6アルキル、-CONR4C3-C6シクロアルキル、ヘテロアリール、アリール、ハロアルコキシ、-C1-C6アルキルC3-C10シクロアルキル、オキソ、-C1-C6アルキルヘテロアリール、-NR4COC1-C6アルキルから独立して選択され、ここで、該-C1-C6アルキルNR4COC3-C6シクロアルキル、-C1-C6アルキルCONR4C3-C6シクロアルキル、-C1-C6アルキルCONR4アリール、-C1-C6アルキルシクロヘテロアルキル、-C1-C6アルキルCOシクロヘテロアルキル、C3-C6シクロアルキル、シクロヘテロアルキル、ヘテロアリール、-C1-C6アルキルC3-C10シクロアルキルは、置換されていないか又はアルコキシ、CN、-C1-C6アルキルOH、ハロゲン、C1-C6アルキル、ハロC1-C6アルキル、オキソ、OH、CN、C1-C6アルキルCN、-COC1-C6アルキル及びC3-C6シクロアルキルからなる群から選択される1~3の置換基で置換されており;
R3は、C1-C6アルキル又はハロC1-C6アルキルであり;
R4は、C1-C6アルキル又は水素であり;
mは、0、1又は2であり;及び、
nは、0、1、2又は3である〕
で表される化合物又はその薬学的に許容される塩である。
Aは、アリール、C3-C10シクロアルキル、ヘテロアリール又はシクロヘテロアルキルであり;
Lは、直鎖又は分枝鎖の(C1-C5)アルキレニルであり、ここで、L中の1以上の-CH2-基は、O及びNHからなる群から選択される部分で独立して置き換えられてもよく;
R1の各存在は、ハロゲン、C1-C6アルキル又はシクロヘテロアルキルから独立して選択され;
R2の各存在は、-C1-C6アルキルNR4COC3-C6シクロアルキル、-C1-C6アルキルNR4COC1-C6アルキル、-C1-C6アルキルCONR4C1-C6アルキル、ハロゲン、アルコキシ、-C1-C6アルキルシクロヘテロアルキル、-C1-C6アルキルCONR4アリール、C1-C6アルキル、-C1-C6アルキルCOシクロヘテロアルキル、-C1-C6アルキルCONR4ヘテロアリール、-C1-C6アルキルNR4SO2C1-C6アルキル、-C1-C6アルキルNR4SO2C3-C6シクロアルキル、C3-C6シクロアルキル、-C1-C6アルキルCONR4C3-C6シクロアルキル、シクロヘテロアルキル、ハロC1-C6アルキル、-CONR4ハロアルキル、-COシクロヘテロアルキル、CN、-CONR4C1-C6アルキル、-CONR4C3-C6シクロアルキル、ヘテロアリール、アリール、ハロアルコキシ、-C1-C6アルキルC3-C10シクロアルキル、オキソ、-C1-C6アルキルヘテロアリール、-NR4COC1-C6アルキルから独立して選択され、ここで、該-C1-C6アルキルNR4COC3-C6シクロアルキル、-C1-C6アルキルCONR4C3-C6シクロアルキル、-C1-C6アルキルCONR4アリール、-C1-C6アルキルシクロヘテロアルキル、-C1-C6アルキルCOシクロヘテロアルキル、C3-C6シクロアルキル、シクロヘテロアルキル、ヘテロアリール、-C1-C6アルキルC3-C10シクロアルキルは、置換されていないか又はアルコキシ、CN、-C1-C6アルキルOH、ハロゲン、C1-C6アルキル、ハロC1-C6アルキル、オキソ、OH、CN、-C1-C6アルキルCN、COC1-C6アルキル及びC3-C6シクロアルキルからなる群から選択される1~3の置換基で置換されており;
R3は、C1-C6アルキル又はハロC1-C6アルキルであり;
R4は、C1-C6アルキル又は水素であり;
mは、0、1又は2であり;及び、
nは、0、1、2又は3である〕
で表される化合物又はその薬学的に許容される塩である。
Aは、アリール、C3-C10シクロアルキル、ヘテロアリール又はシクロヘテロアルキルであり;
Lは、直鎖又は分枝鎖の(C1-C5)アルキレニルであり、ここで、L中の1以上の-CH2-基は、O及びNHからなる群から選択される部分で独立して置き換えられてもよく;
R1の各存在は、ハロゲン、C1-C6アルキル又はシクロヘテロアルキルから独立して選択され;
R2の各存在は、-C1-C6アルキルNR4COC3-C6シクロアルキル、-C1-C6アルキルNR4COC1-C6アルキル、-C1-C6アルキルCONR4C1-C6アルキル、ハロゲン、アルコキシ、-C1-C6アルキルシクロヘテロアルキル、-C1-C6アルキルCONR4アリール、C1-C6アルキル、-C1-C6アルキルCOシクロヘテロアルキル、-C1-C6アルキルCONR4ヘテロアリール、-C1-C6アルキルNR4SO2C1-C6アルキル、-C1-C6アルキルNR4SO2C3-C6シクロアルキル、C3-C6シクロアルキル、-C1-C6アルキルCONR4C3-C6シクロアルキル、シクロヘテロアルキル、ハロC1-C6アルキル、-CONR4ハロアルキル、-COシクロヘテロアルキル、CN、-CONR4C1-C6アルキル、-CONR4C3-C6シクロアルキル、ヘテロアリール、アリール、ハロアルコキシ、-C1-C6アルキルC3-C10シクロアルキル、オキソ、-C1-C6アルキルヘテロアリール、-NR4COC1-C6アルキルから独立して選択され、ここで、該-C1-C6アルキルNR4COC3-C6シクロアルキル、-C1-C6アルキルCONR4C3-C6シクロアルキル、-C1-C6アルキルCONR4アリール、C1-C6アルキルシクロヘテロアルキル、C1-C6アルキルCOシクロヘテロアルキル、C3-C6シクロアルキル、シクロヘテロアルキル、ヘテロアリール、-C1-C6アルキルC3-C10シクロアルキルは、置換されていないか又はアルコキシ、CN、-C1-C6アルキルOH、ハロゲン、C1-C6アルキル、ハロC1-C6アルキル、オキソ、OH、CN、-C1-C6アルキルCN、-COC1-C6アルキル及びC3-C6シクロアルキルからなる群から選択される1~3の置換基で置換されており;
R3は、C1-C6アルキル又はハロC1-C6アルキルであり;
R4は、C1-C6アルキル又は水素であり;
mは、0、1又は2であり;及び、
nは、0、1、2又は3である〕
で表される化合物又はその薬学的に許容される塩である。
用語「アルキレン」又は「アルキレニル」は、それ自体又は別の置換基の一部として、記載された数の炭素原子を有する二価の直鎖又は分枝鎖炭化水素ラジカルを意味する。例えば、-(C1-C5)アルキレニルには、例えば、-CH2-、-CH2CH2-、-CH2CH2CH2-、-CH2CH2CH2CH2-、-CH2CH(CH3)CH2-又は-CH2CH2CH2CH2CH2-が包含される。
IL4I1関連疾患を予防、治療又は改善する方法も本発明に包含される。本明細書中に記載されている化合物は、癌などの様々なIL4I1関連疾患の予防、治療又は改善において有効であり得る。本明細書中に記載されているのは、患者におけるIL4I1発現細胞を提示する癌を治療する方法である。本明細書中に記載されているのは、患者におけるIL4I1発現細胞を示す癌を予防する方法である。本明細書中に記載されているのは、患者におけるIL4I1発現細胞を提示する癌を改善する方法である。
本明細書中に記載されている化合物は、経口又は非経口で投与することができる。本明細書中に記載されている化合物は、投与に適した剤形に製剤化することにより、上記疾患の予防、治療又は療法のための医薬組成物として使用することができる。
本発明の化合物は、他の治療薬と組み合わせて、上記で記載した疾患、障害及び状態を予防又は治療する方法においてさらに有用である。
「PD-1アンタゴニスト」は、癌細胞において発現するPD-L1と免疫細胞(T細胞、B細胞又はNKT細胞)において発現するPD-1との結合をブロックし、好ましくは、癌細胞において発現するPD-L2と免疫細胞において発現するPD-1との結合もブロックする、任意の化合物又は生体分子を意味する。PD-1及びそのリガンドの代替的な名称又は同義語としては、以下のものなどがある:PD-1に関しては、PDCD1、PD1、CD279、及び、SLEB2;PD-Llに関しては、PDCD1L1、PDL1、B7H1、B7-4、CD274、及び、B7-H;及び、PD-L2に関しては、PDCD1L2、PDL2、B7-DC、Btdc、及び、CD273。ヒト個体が治療される本発明の治療方法、薬剤及び使用のいずれにおいても、PD-1アンタゴニストは、ヒトPD-L1のヒトPD-1への結合をブロックし、好ましくは、ヒトPD-L1及びPD-L2の両方のヒトPD-1への結合をブロックする。ヒトPD-1アミノ酸配列は、NCBI Locus No.:NP 005009に見出すことができる。ヒトPD-L1及びPD-L2のアミノ酸配列は、それぞれ、NCBI Locus No.:NP_054862及びNP_079515に見出すことができる。
代謝拮抗物質の例としては、限定するものではないが、クラリビン(2-クロロデオキシアデノシン、商品名「LEUSTATIN」で販売されている)、5-フルオロウラシル(商品名「ADRUCIL」で販売されている)、6-チオグアニン(商品名「PURINETHOL」で販売されている)、ペメトレキセド(商品名「ALIMTA」で販売されている)、シタラビン(アラビノシルシトシン(Ara-C)としても知られている、商品名「CYTOSAR-U」で販売されている)、シタラビンリポソーム(Liposomal Ara-Cとしても知られている、商品名「DEPOCYT」で販売されている)、デシタビン(商品名「DACOGEN」で販売されている)、ヒドロキシ尿素(商品名「HYDREA」、「DROXIA」及び「MYLOCEL」で販売されている)、フルダラビン(商品名「FLUDARA」で販売されている)、フロクスウリジン(商品名「FUDR」で販売されている)、クラドリビン(2-クロロデオキシアデノシン(2-CdA)としても知られている、商品名「LEUSTATIN」で販売されている)、メトトレキサート(アメトプテリン、メトトレキサートナトリウム(MTX)としても知られている、商品名「RHEUMATREX」及び「TREXALL」で販売されている)、及び、ペントスタチン(商品名「NIPENT」で販売されている)などを挙げることができる。
式Iで表される特定の化合物は、CDIの存在下で、ジアミノ4を5に変換させることによって合成した。次いで、脱保護により、5を6に変換させた。対応する酸、酸無水物、スルホニルクロリド又は無水スルホン酸とのカップリングにより合成が完了した。
式Iで表される特定の化合物は、対応する臭化アリールを用いて、イリジウム及びニッケルが触媒する脱炭酸カップリング条件下でアルキル酸7を8に変換させることによって合成した。必要に応じて、脱保護により合成が完了した。
式Iで表される特定の化合物は、対応する臭化アリールを用いて、イリジウム及びニッケルが触媒する脱炭酸カップリング条件下でアルキル酸9を10に変換させることによって合成した。10の脱保護により化合物11が得られた。対応する酸とのカップリングにより合成が完了した。
式Iで表される特定の化合物は、銅が触媒するアリールアミノ化反応とそれに続く分子内環化反応を用いて、カルバメート19を20に変換させることによって合成した。20を脱保護して、21が得られた。アミドカップリングを用いて合成が完了した。
式Iで表される特定の化合物は、パラジウムが触媒するスズキ反応でボロネート25を26に変換させることによって合成した。パラジウムが触媒するシクロプロパン化反応によって、26を27に変換させた。脱保護により合成が完了した。
式Iで表される特定の化合物は、トリホスゲンの存在下で酸28を29に変換させることによって合成した。アジ化ナトリウムの存在下で、29を30に変換させた。クルチウス転位とそれに続く分子内環化反応により合成が完了した。
式Iで表される特定の化合物は、ハロゲン化ベンジルを用いるアルキル化でアミン31を32に変換させることによって合成した。アミンを用いるアルキル化によって、32を33に変換させた。脱保護により合成が完了した。
式Iで表される特定の化合物は、ジ-ヨードアルキル化合物を用いるアルキル化でアミン34を35に変換させることによって合成した。トリフェニルホスフィンを用いるアルキル化によって、35を36に変換させた。ウィッティヒ反応によって、36を37に変換させた。脱保護によって、37を38に変換させた。パラジウムが触媒する水素化反応によって、合成が完了した。
式Iで表される特定の化合物は、ハロゲン化ベンジルを用いるアルキル化でアミン39を40に変換させることによって合成した。ニッケルが触媒する還元的カップリングによって、40を41に変換させた。脱保護により合成が完了した。
中間体2:
2-(3-(tert-ブトキシカルボニル)-2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)酢酸
段階B: 2-(3-(tert-ブトキシカルボニル)-2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)酢酸
段階B: 2-オキソ-3-(4-((2-オキソピロリジン-1-イル)メチル)ベンジル)-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-カルボン酸tert-ブチル
実施例2:
1-(4-((2-オキソ-2,5-ジヒドロ-1H-ピロール-1-イル)メチル)ベンジル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オンの調製
段階D: 1-(4-((2-オキソ-2,5-ジヒドロ-1H-ピロール-1-イル)メチル)ベンジル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オン
実施例3:
1-(4-((1,3,4-オキサジアゾール-2-イル)メチル)ベンジル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オンの調製
実施例1の段階B-段階Cで概説した手順を使用して、以下の段階C及び段階Dにおいて、2-(4-ブロモベンジル)-1,3,4-オキサジアゾールから最終生成物1-(4-((1,3,4-オキサジアゾール-2-イル)メチル)ベンジル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オンを合成した。
LC/MS (m/z): 429 (M+Na)+
段階D: 1-(4-((1,3,4-オキサジアゾール-2-イル)メチル)ベンジル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オン
1H NMR (600 MHz, DMSO-d6) δ 10.94 (s, 1H), 9.10 (s, 1H), 7.31 - 7.22 (m, 4H), 7.03 - 6.90 (m, 4H), 4.97 (s, 2H), 4.25 (s, 2H). LC/MS (m/z): 306 (M+H)+
実施例4:
1-(4-((1,3,4-オキサジアゾール-2-イル)メチル)-3-クロロベンジル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オンの調製
LC/MS (m/z): 265 (M+H)+
段階B: 2-(4-ブロモ-2-クロロベンジル)-1,3,4-オキサジアゾール
LC/MS (m/z): 275 (M+H)+
段階C: 3-(4-((1,3,4-オキサジアゾール-2-イル)メチル)-3-クロロベンジル)-2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-カルボン酸tert-ブチル
LC/MS (m/z): 341 (M+H)+(Bocの喪失として実測される)
段階D: 1-(4-((1,3,4-オキサジアゾール-2-イル)メチル)-3-クロロベンジル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オン
1H NMR (600 MHz, DMSO-d6) δ 10.98 (s, 1H), 9.11 (s, 1H), 7.46 - 7.40 (m, 2H), 7.27 (d, J = 7.9 Hz, 1H), 7.08 (d, J = 7.8 Hz, 1H), 7.03 - 6.92 (m, 3H), 5.01 (s, 2H), 4.36 (s, 2H). LC/MS (m/z): 341 (M+H)+
実施例5:
N-(3-メトキシ-4-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)ベンジル)アセトアミドの調製
実施例1の段階B-段階Cで概説した手順を使用して、N-(4-ブロモ-3-メトキシベンジル)アセトアミドから最終生成物N-(3-メトキシ-4-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)ベンジル)アセトアミドを合成した。
LC/MS (m/z): 326 (M+H)+ (Bocの喪失として実測される)
段階C: N-(3-メトキシ-4-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)ベンジル)アセトアミド
1H NMR (400 MHz, MeOH-d4) δ 7.10-7.05 (m, 1H), 7.05-7.00 (m, 1H), 7.00-6.90 (m, 4H), 6.78 (d, J = 6.7 Hz, 1H), 5.04 (s, 2H), 4.31 (s, 2H), 3.89 (s, 3H), 1.97 (s, 3H). LCMS (ESI) m/z: 326 [M+H]+.
実施例6:
N-((5-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)チオフェン-2-イル)メチル)メタンスルホンアミドの調製
段階B: N-((5-ブロモチオフェン-2-イル)メチル)メタンスルホンアミド
実施例1の段階B-段階Cで概説した手順を使用して、以下の段階C-段階Dにおいて、N-((5-ブロモチオフェン-2-イル)メチル)メタンスルホンアミドから最終生成物N-((5-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)チオフェン-2-イル)メチル)メタンスルホンアミドを合成した。
LCMS (ESI) m/z: 338 [M+H]+ (Bocの喪失として実測される)
段階D: N-((5-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)チオフェン-2-イル)メチル)メタンスルホンアミド
1H NMR (400 MHz, MeOH-d4) δ 7.15-7.09 (m, 1H), 7.08-7.02 (m, 3H), 7.00 (d, J = 3.4 Hz, 1H), 6.88 (d, J = 3.4 Hz, 1H), 5.21 (s, 2H), 4.34 (s, 2H), 2.77 (s, 3H). LCMS (ESI) m/z: 338 [M+H]+
表1中の実施例は、適切な臭化アリール出発物質を使用し、実施例1の段階B-段階Cに記載されている方法に準じて合成した。
実施例12:
N-(4-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)ベンジル)メタンスルホンアミドの調製
段階B: 3-(4-(メチルスルホンアミドメチル)ベンジル)-2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-カルボン酸tert-ブチル
段階C: N-(4-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)ベンジル)メタンスルホンアミド
実施例13:
N-メチル-5-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)チオフェン-3-カルボキサミドの調製
段階B: 3-((4-(メチルカルバモイル)チオフェン-2-イル)メチル)-2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-カルボン酸tert-ブチル
段階C: N-メチル-5-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)チオフェン-3-カルボキサミド
1H NMR (500MHz, MeOH-d4) δ 7.89 (d, J = 1.2 Hz, 1H), 7.46 (s, 1H), 7.17-7.12 (m, 1H), 7.10-7.02 (m, 3H), 5.24 (s, 2H), 2.85 (s, 3H).
表2中の実施例は、適切なBr出発物質を使用し、実施例13の段階Bに記載されている方法に準じて合成した。
表3中の実施例は、上記で記載されている条件又は標準的なアミドカップリング条件(例えば、HATU/DIEA)を使用して、実施例15に記載されている方法に従い、段階Aにおいて適切な置換(4-ブロモフェニル)メタンアミン出発物質を用いて合成した。
実施例19:
1-(3-ヨード-4-((2-オキソピロリジン-1-イル)メチル)ベンジル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オンの調製
段階D: 1-(3-ヨード-4-((2-オキソピロリジン-1-イル)メチル)ベンジル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オン
実施例20:
1-(4-((3,3-ジオキシド-1,3,4-オキサチアジナン-4-イル)メチル)ベンジル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オンの調製
表4中の実施例は、適切な臭化アリール出発物質を使用し、実施例18に記載されている方法に準じて合成した;あるいは、所望の臭化アリールを形成させた後、カラムクロマトグラフィーを用いて段階的に実施することもできる。
(代替え的に、塩基として2-tert-ブチル-1,1,3,3-テトラメチルグアニジンを使用することも可能である)。
(代替え的に、これらの手順においても、塩基として2-tert-ブチル-1,1,3,3-テトラメチルグアニジンを使用することも可能であり、及び、アセトニトリル/水の勾配(TFA調節剤含有)で溶離させるHPLCで精製することも可能である)。
表5中の実施例は、適切な臭化アリール出発物質を使用して、実施例27に記載されている方法に準じて合成した。
段階B: 5-ブロモ-2-(ブロモメチル)-3-クロロチオフェン
実施例27で概説した手順を使用して、1-((5-ブロモ-3-クロロチオフェン-2-イル)メチル)ピロリジン-2-オンから最終生成物1-((4-クロロ-5-((2-オキソピロリジン-1-イル)メチル)チオフェン-2-イル)メチル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オンを合成した。
1H NMR (400MHz, MeOH-d4) δ 7.15-7.10 (m, 1H), 7.08-7.06 (m, 3H), 6.99 (s, 1H), 5.16 (s, 2H), 4.53 (s, 2H), 3.35 (t, J = 7.0 Hz, 2H), 2.38-2.30 (m, 2H), 2.04-1.92 (m, 2H). LCMS (ESI) m/z: 362 [M+H]+.
実施例37:
N,N-ジメチル-2-(6-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)ピリジン-3-イル)アセトアミドの調製
実施例27で概説した手順を使用して、2-(6-ブロモピリジン-3-イル)-N,N-ジメチルアセトアミドから最終生成物N,N-ジメチル-2-(6-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)ピリジン-3-イル)アセトアミドを合成した。
1H NMR (500MHz, MeOH-d4) δ 8.53 (br s, 1H), 8.01-7.99 (m, 1H), 7.51 (d, J = 8.0 Hz, 1H), 7.14-7.07 (m, 2H), 7.05-7.00 (m, 2H), 5.32 (s, 2H), 3.91 (s, 2H), 3.14 (s, 3H), 2.95 (s, 3H). LCMS (ESI) m/z: 311 [M+H]+.
実施例38:
N-((3-クロロ-5-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)チオフェン-2-イル)メチル)アセトアミドの調製
段階E: N-((3-クロロ-5-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)チオフェン-2-イル)メチル)アセトアミド
実施例39:
N-((3-クロロ-5-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)チオフェン-2-イル)メチル)メタンスルホンアミド
段階E: N-((3-クロロ-5-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)チオフェン-2-イル)メチル)メタンスルホンアミド
実施例40:
N-((3-メチル-5-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)チオフェン-2-イル)メチル)アセトアミド
段階D: N-((3-メチル-5-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)チオフェン-2-イル)メチル)アセトアミド
実施例41:
1-((6-((2-オキソピロリジン-1-イル)メチル)ピリジン-3-イル)メチル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オンの調製
段階B: 1-((6-((2-オキソピロリジン-1-イル)メチル)ピリジン-3-イル)メチル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オン
実施例42:
5-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)-1H-インダゾール-3-カルボニトリルの調製
実施例43:
1-(4-((3,3-ジフルオロ-2-オキソピロリジン-1-イル)メチル)ベンジル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オンの調製
段階B: 1-(4-((3,3-ジフルオロ-2-オキソピロリジン-1-イル)メチル)ベンジル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オン
実施例44:
N-(2-クロロ-4-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)ベンジル)アセトアミドの調製
段階B: 1-(4-(アミノメチル)-3-クロロベンジル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オン
実施例45:
N-(6-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)-2,3-ジヒドロ-1H-インデン-1-イル)アセトアミドの調製
段階B: 1-((3-アミノ-2,3-ジヒドロ-1H-インデン-5-イル)メチル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オン
段階C: N-(6-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)-2,3-ジヒドロ-1H-インデン-1-イル)アセトアミド
段階D: N-(6-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)-2,3-ジヒドロ-1H-インデン-1-イル)アセトアミド
実施例46:
N-メチル-5-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)-2,3-ジヒドロ-1H-インデン-1-カルボキサミド
段階B: N-メチル-5-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)-2,3-ジヒドロ-1H-インデン-1-カルボキサミド
段階C: N-メチル-5-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)-2,3-ジヒドロ-1H-インデン-1-カルボキサミド
表6中の実施例は、実施例46に記載されている方法に従い、段階Aにおいて適切な置換臭化物出発物質及びアミン出発物質を使用して合成した。
表7中の実施例は、適切な置換(4-ブロモフェニル)メタンアミン出発物質を使用して、実施例49に記載されている方法に準じて合成した。
段階B: 1-(インドリン-5-イルメチル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オン
実施例53:
1-(4-((4-メチル-4H-1,2,4-トリアゾール-3-イル)メチル)ベンジル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オンの調製
実施例54:
1-(4-((1,3,4-オキサジアゾール-2-イル)メチル)-3-メチルベンジル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オンの調製
段階C: 1-(4-((1,3,4-オキサジアゾール-2-イル)メチル)-3-メチルベンジル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オン
実施例55:
1-((2,3-ジヒドロ-1H-インデン-5-イル)メチル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オンの調製
実施例56:
1-(ピリジン-3-イルメチル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オンの調製
表8中の実施例は、適切なアミン出発物質を使用して、実施例55に記載されている方法に準じて合成した。
段階B: 1-(4-(アミノメチル)ベンジル)-6-クロロ-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オン
段階C: N-(4-((3-アセチル-6-クロロ-2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)ベンジル)アセトアミド
実施例65:
N-(4-((6-メチル-2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)ベンジル)アセトアミドの調製
段階C: N-(4-((6-メチル-2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)ベンジル)アセトアミド
実施例66:
2-(4-((6-フルオロ-2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)フェニル)-N,N-ジメチルアセトアミドの調製
段階D: 2-(4-((6-フルオロ-2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)フェニル)-N,N-ジメチルアセトアミド
実施例67:
2-(4-((6-フルオロ-2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)フェニル)-N-メチルアセトアミドの調製
段階C: 5-フルオロ-3-(4-(2-メトキシ-2-オキソエチル)ベンジル)-2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-カルボン酸tert-ブチル
段階E: 2-(4-((6-フルオロ-2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)フェニル)-N-メチルアセトアミド
実施例68:
1-ベンジル-4-フルオロ-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オンの調製
表9中の実施例は、実施例68で記載され方法に従い、段階Aにおいて適切な置換(2-ブロモフェニル)カルバミン酸メチル出発物質を使用し、及び、適切な置換メタンアミンを使用して、合成した。
表10中の実施例は、適切な臭化ベンジル出発物質を使用して、実施例71で記載した方法に準じて合成した。
段階B: 3-(4-((N-メチルアセトアミド)メチル)ベンジル)-2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-カルボン酸tert-ブチル
段階C: N-メチル-N-(4-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)ベンジル)アセトアミド
表11中の実施例は、適切なアミド(又は、ラクタム)出発物質を使用して、実施例73で記載した方法に準じて合成した。
段階F: N-メチル-N-(4-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)ベンジル)シクロプロパンスルホンアミド
実施例76:
N-(4-((3-(ジフルオロメチル)-2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)ベンジル)アセトアミドの調製
段階B: (4-((3-(ジフルオロメチル)-2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)フェニル)メタンアミニウムクロリド
段階C: N-(4-((3-(ジフルオロメチル)-2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)ベンジル)アセトアミド
実施例77:
N-(4-((3-(ジフルオロメチル)-2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)ベンジル)メタンスルホンアミドの調製
実施例78:
1-ベンジル-3-(ジフルオロメチル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オンの調製
実施例79:
1-((3-クロロ-5-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)ピリジン-2-イル)メチル)シクロブタン-1-カルボニトリルの調製
段階B: 3-((5-クロロ-6-((1-シアノシクロブチル)メチル)ピリジン-3-イル)メチル)-2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-カルボン酸tert-ブチル
段階C: 1-((3-クロロ-5-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)ピリジン-2-イル)メチル)シクロブタン-1-カルボニトリル
実施例80:
1-(3-(4-メチルピペラジン-1-イル)ベンジル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オンの調製
段階B: 1-(3-(4-メチルピペラジン-1-イル)ベンジル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オン
実施例81:
1-(4-((5-(ヒドロキシメチル)-1H-1,2,3-トリアゾール-1-イル)メチル)ベンジル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オンの調製
段階B: 3-(4-(アジドメチル)ベンジル)-2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-カルボン酸tert-ブチル
段階C: 3-(4-((4又は5-(ヒドロキシメチル)-1H-1,2,3-トリアゾール-1-イル)メチル)ベンジル)-2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-カルボン酸tert-ブチル
段階D: 1-(4-((4又は5-(ヒドロキシメチル)-1H-1,2,3-トリアゾール-1-イル)メチル)ベンジル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オン
段階E: 1-(4-((5-(ヒドロキシメチル)-1H-1,2,3-トリアゾール-1-イル)メチル)ベンジル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オン
実施例82:
1-(4-((1H-1,2,3-トリアゾール-1-イル)メチル)ベンジル)-1H-ベンゾ[d]イミダゾール-2(3H)-オンの調製
段階B: 3-(4-((1H-1,2,3-トリアゾール-1-イル)メチル)ベンジル)-2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-カルボン酸tert-ブチル
段階C: 1-(4-((1H-1,2,3-トリアゾール-1-イル)メチル)ベンジル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オン
表12中の実施例は、実施例82で記載した方法に従い、段階Bにおいて、適切な条件下(例えば、K2CO3/MeCN/70℃/16時間)で、適切な置換出発物質を使用して合成した。
段階B: 6-フルオロ-1-(4-((2-オキソピロリジン-1-イル)メチル)ベンジル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オン
実施例85:
5-フルオロ-1-(4-((2-オキソピロリジン-1-イル)メチル)ベンジル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オンの調製
実施例86:
1-(2-メトキシベンジル)-6-メチル-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オンの調製
段階B: 1-(2-メトキシベンジル)-6-メチル-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オン
実施例87:
1-(1-フェニルエチル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オンの調製
LCMS (ESI) m/z: 283 [M+H]+ (tBuの喪失として観察される).
段階B: 1-(1-フェニルエチル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オン
1H NMR (500MHz, MeOH-d4) δ 7.42-7.34 (m, 4H), 7.31-7.26 (m, 1H), 7.11-7.07 (m, 1H), 7.02 (t, J = 7.7 Hz, 1H), 6.90 (t, J = 7.7 Hz, 1H), 6.77 (d, J = 7.9 Hz, 1H), 5.81 (q, J = 7.2 Hz, 1H), 1.92 (d, J = 7.2 Hz, 3H). LCMS (ESI) m/z : 239 [M+H]+.
実施例88:
1-(1-シクロヘキシルエチル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オンの調製
LCMS (ESI) m/z: 345 [M+H]+.
段階B: 1-(1-シクロヘキシルエチル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オン
1H NMR (500 MHz , MeOH-d4) δ 7.25-7.23 (m , 1 H) , 7.09-7.06 (m , 3H) , 4.19-4.13 (m , 1H) , 2.08-2.05 (m , 2H) , 1.86-1.84 (m, 1H), 1.68-1.62 (m, 2H), 1.53 (d , J = 7.0 Hz, 3H), 1.35-1.32 (m , 2H), 1.13-1.08 (m, 3H), 0.93-0.92 (m, 1H). LCMS (ESI) m/z: 245 [M+H+].
実施例89:
1-メチル-3-(3-(トリフルオロメトキシ)ベンジル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オンの調製
実施例90:
5-クロロ-1-(3-メトキシベンジル)-3-メチル-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オンの調製
LCMS (ESI) m/z: 389 [M+H]+.
段階B: 5-クロロ-1-(3-メトキシベンジル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オン
LCMS (ESI) m/z: 289 [M+H]+.
段階C: 5-クロロ-1-(3-メトキシベンジル)-3-メチル-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オン
実施例91:
1-(2-メトキシベンジル)-7-メチル-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オンの調製
実施例92:
1-(2-メトキシベンジル)-4-メチル-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オンの調製
LCMS (ESI) m/z: 273 [M+H]+.
段階B: N 1 -(2-メトキシベンジル)-6-メチルベンゼン-1,2-ジアミン
LCMS (ESI) m/z: 243 [M+H]+.
段階C: 1-(2-メトキシベンジル)-4-メチル-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オン
1H NMR (400 MHz, CDCl3) δ 9.59 (br s, 1H), 7.25-7.23 (m, 1H), 7.14-7.12 (m, 1H), 6.93-6.79 (m, 5H), 5.12 (s, 2H), 3.91 (s, 3H), 2.40 (s, 3H). LCMS (ESI) m/z: 269 [M+H]+.
実施例93:
1-ベンジル-4-(ピロリジン-1-イル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オンの調製
実施例94:
N-(4-((6-フルオロ-2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)ベンジル)アセトアミドの調製
段階C: (4-((6-フルオロ-2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)ベンジル)カルバミン酸tert-ブチル
段階D: 1-(4-(アミノメチル)ベンジル)-6-フルオロ-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オン
実施例95:
N-(4-((6-フルオロ-2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)ベンジル)プロパン-1-スルホンアミドの調製
実施例96:
1-メトキシ-N-(4-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)ベンジル)シクロプロパン-1-カルボキサミドの調製
段階E: 1-メトキシ-N-(4-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)ベンジル)シクロプロパン-1-カルボキサミド
実施例97:
1-(3-(キノリン-8-イルオキシ)プロピル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オンの調製
実施例98:
N-(((1r,4r)-4-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)シクロヘキシル)メチル)メタンスルホンアミドの調製
段階C: (((1r,4r)-4-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)シクロヘキシル)メチル)カルバミン酸tert-ブチル
段階E: N-(((1r,4r)-4-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)シクロヘキシル)メチル)メタンスルホンアミド
1H NMR (400 MHz, CD3OD) δ 7.15-7.00 (m, 4H), 3.73 (d, J = 7.4 Hz, 2H), 2.92-2.84 (m, 5H), 1.87-1.84 (m, 3H), 1.75- 1.73 (m, 2H), 1.46 (br s, 1H), 1.19-1.05 (m, 2H), 1.01-0.89 (m, 2H).
実施例99:
N-((1r,4r)-4-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)シクロヘキシル)アセトアミドの調製
段階B: ((1s,4s)-4-(((2-アミノフェニル)アミノ)メチル)シクロヘキシル)カルバミン酸tert-ブチル
段階C: ((1s,4s)-4-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)シクロヘキシル)カルバミン酸tert-ブチル
段階D: 1-(((1s,4s)-4-アミノシクロヘキシル)メチル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オン
段階E: N-((1s,4s)-4-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)シクロヘキシル)アセトアミド
実施例100:
実施例101:
3-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)-N-(2,2,2-トリフルオロエチル)ベンズアミドの調製
実施例102:
1-(3-(アゼチジン-1-カルボニル)ベンジル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オンの調製
実施例103:
2-(3-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)フェニル)-N-(ピリジン-3-イル)アセトアミドの調製
実施例104:
N-(3-シアノフェニル)-2-(3-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)フェニル)アセトアミドの調製
実施例105:
N,N-ジメチル-2-(3-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)フェニル)アセトアミドの調製
実施例106:
N-(3-フルオロシクロペンチル)-2-(4-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)フェニル)アセトアミドの調製
実施例107:
N-メチル-2-(4-((2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)メチル)フェニル)アセトアミドの調製
表13中の実施例は、対応するアミン出発物質を使用して、実施例107に記載されている方法準じて合成した。
表14中の実施例は、適切なBr/Clベンゼン出発物質を使用して、実施例109に記載されている方法に準じて合成した。
段階B: 3-((2-(5-メチルピリジン-2-イル)シクロプロピル)メチル)-2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-カルボン酸tert-ブチル
段階D: 1-((2-(5-メチルピリジン-2-イル)シクロプロピル)メチル)-1H-ベンゾ[d]イミダゾール-2(3H)-オン
実施例112:
1-ベンジル-1,3-ジヒドロ-2H-チエノ[2,3-d]イミダゾール-2-オンの調製
段階B: 1-ベンジル-2H-チエノ[3,2-d][1,3]オキサジン-2,4(1H)-ジオン
段階C: 3-(ベンジルアミノ)チオフェン-2-カルボニルアジド
表15中の実施例は、実施例112に記載されている方法に従い、段階Bにおいて、対応する市販の出発物質を使用して合成した。
段階B: (3-(3-(tert-ブトキシカルボニル)-2-オキソ-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-イル)プロピル)トリフェニルホスホニウムヨージド
段階C: 2-オキソ-3-(4-(キノリン-8-イル)ブタ-3-エン-1-イル)-2,3-ジヒドロ-1H-ベンゾ[d]イミダゾール-1-カルボン酸tert-ブチル
段階E: 1-(4-(キノリン-8-イル)ブチル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オン
1HNMR (500 MHz, CDCl3) δ 10.59 (br s, 1H), 9.62 (br d, J=4.5 Hz, 1H), 8.68 (d, J=7.5 Hz, 1H), 7.95-7.87 (m, 2H), 7.80 (d, J=6.5 Hz, 1H), 7.72-7.66 (m, 1H), 7.20-7.14 (m, 1H), 7.12-6.98 (m, 3H), 4.08 (br t, J=6.5 Hz, 2H), 3.50-3.37 (m, 2H), 2.02-1.91 (m, 2H), 1.76-1.62 (m, 2H).
実施例115:
1-((1-(ピリジン-2-イル)ピペリジン-4-イル)メチル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オンの調製
段階B: 1-(ピペリジン-4-イルメチル)-1,3-ジヒドロ-2H-ベンゾ[d]イミダゾール-2-オン
アッセイ
IL4I1酵素アッセイ
インターロイキン4誘導タンパク質1(IL4I1)は、芳香族残基(Phe、Trp及びTyr)の酸化を触媒するL-アミノオキシダーゼである:L-アミノ酸+H2O+O2 → 2-オキソ酸+NH3+H2O2。IL4I1及び基質を加えると、等モルのH2O2と対応するα-ケト酸が生成される。このアッセイでは、IL4I1によって生成された過酸化水素は、蛍光シグナルの形態で検出可能なレゾルフィン生成物を生成するAmplex Red(10-アセチル-3,7-ジヒドロキシフェノキサジン)及びホースペルオキシダーゼ(HRP)との共役反応を通して検出される。IL4I1に対する小分子の阻害効果の評価(EC50)は、H2O2の生成を阻害する該化合物の有効性によって測定される。
Claims (25)
- Lは、-CH2-、-CH2CH2-、-CH2CH2CH2CH2-、-CH2CH2CH2O-又は-CHCH3-である、請求項1に記載の化合物又はその薬学的に許容される塩。
- Aは、フェニルである、請求項1に記載の化合物又はその薬学的に許容される塩。
- mは、0である、請求項1に記載の化合物又はその薬学的に許容される塩。
- mは、1又は2であり、及び、R1は、フッ素、塩素、ピロリジン、メチル又はエチルである、請求項1に記載の化合物又はその薬学的に許容される塩。
- R3は、水素、メチル又はジフルオロメチルである、請求項1に記載の化合物又はその薬学的に許容される塩。
- 癌を治療するための薬剤の製造における請求項1又は請求項7に記載の化合物又はその薬学的に許容される塩の使用。
- 医薬組成物であって、請求項1又は請求項7に記載の化合物又はその薬学的に許容される塩及び薬学的に許容される担体を含んでいる、前記医薬組成物。
- 医薬組成物であって、請求項1又は請求項7に記載の化合物及び薬学的に許容される担体を含んでいる、前記医薬組成物。
- 癌を治療するための薬剤の製造における請求項12に記載の化合物又はその薬学的に許容される塩の使用。
- 医薬組成物であって、請求項12に記載の化合物又はその薬学的に許容される塩及び薬学的に許容される担体を含んでいる、前記医薬組成物。
- 医薬組成物であって、請求項11に記載の化合物及び薬学的に許容される担体を含んでいる、前記医薬組成物。
- 癌を治療するための薬剤の製造における請求項17に記載の化合物又はその薬学的に許容される塩の使用。
- 医薬組成物であって、請求項17に記載の化合物又はその薬学的に許容される塩及び薬学的に許容される担体を含んでいる、前記医薬組成物。
- 医薬組成物であって、請求項16に記載の化合物及び薬学的に許容される担体を含んでいる、前記医薬組成物。
- 癌を治療するための薬剤の製造における請求項22に記載の化合物又はその薬学的に許容される塩の使用。
- 医薬組成物であって、請求項22に記載の化合物又はその薬学的に許容される塩及び薬学的に許容される担体を含んでいる、前記医薬組成物。
- 医薬組成物であって、請求項21に記載の化合物及び薬学的に許容される担体を含んでいる、前記医薬組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US202063020614P | 2020-05-06 | 2020-05-06 | |
US63/020,614 | 2020-05-06 | ||
PCT/US2021/030541 WO2021226003A1 (en) | 2020-05-06 | 2021-05-04 | Il4i1 inhibitors and methods of use |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2023515721A JP2023515721A (ja) | 2023-04-13 |
JP7311720B2 true JP7311720B2 (ja) | 2023-07-19 |
Family
ID=76076510
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2022567075A Active JP7311720B2 (ja) | 2020-05-06 | 2021-05-04 | Il4i1阻害剤及び使用方法 |
Country Status (19)
Country | Link |
---|---|
US (1) | US20230183214A1 (ja) |
EP (1) | EP4146644A1 (ja) |
JP (1) | JP7311720B2 (ja) |
KR (1) | KR20230006898A (ja) |
CN (1) | CN115836054A (ja) |
AR (1) | AR122007A1 (ja) |
AU (1) | AU2021268614A1 (ja) |
BR (1) | BR112022022452B1 (ja) |
CA (1) | CA3177442A1 (ja) |
CL (1) | CL2022003039A1 (ja) |
CO (1) | CO2022016153A2 (ja) |
CR (1) | CR20220565A (ja) |
EC (1) | ECSP22089498A (ja) |
IL (1) | IL297781A (ja) |
MX (1) | MX2022013843A (ja) |
PE (1) | PE20230680A1 (ja) |
TW (1) | TW202202493A (ja) |
WO (1) | WO2021226003A1 (ja) |
ZA (1) | ZA202212095B (ja) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2024149242A1 (zh) * | 2023-01-09 | 2024-07-18 | 成都百裕制药股份有限公司 | 一种杂环化合物及其在医药上的应用 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006048727A1 (en) | 2004-11-02 | 2006-05-11 | Pfizer Products Inc. | Piperazinylphenalkyl lactam/amine ligands for the 5ht1b receptor |
JP2010507664A (ja) | 2006-10-25 | 2010-03-11 | 武田薬品工業株式会社 | ベンズイミダゾール化合物 |
US20190177338A1 (en) | 2017-12-08 | 2019-06-13 | Astrazeneca Ab | Chemical compounds |
Family Cites Families (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TW203049B (ja) * | 1990-04-13 | 1993-04-01 | Yamanouchi Pharma Co Ltd | |
ES2163506T3 (es) * | 1994-06-14 | 2002-02-01 | Pfizer | Derivados de bencimidazolona con actividad dopaminergica central. |
JPH11292720A (ja) * | 1998-04-13 | 1999-10-26 | Nissan Chem Ind Ltd | 縮合イミダゾリノン誘導体を含有する除草剤 |
US6420410B1 (en) * | 1998-11-24 | 2002-07-16 | Cell Pathways, Inc. | Method for treating neoplasia by exposure to N,N′-substituted benzimidazol-2-ones |
PE20010306A1 (es) | 1999-07-02 | 2001-03-29 | Agouron Pharma | Compuestos de indazol y composiciones farmaceuticas que los contienen utiles para la inhibicion de proteina kinasa |
GB0018891D0 (en) | 2000-08-01 | 2000-09-20 | Novartis Ag | Organic compounds |
EP1368458A2 (en) | 2001-02-26 | 2003-12-10 | Pharma Pacific Pty. Ltd. | Interferon-alpha induced gene |
KR100809569B1 (ko) * | 2001-10-02 | 2008-03-04 | 아카디아 파마슈티칼스 인코포레이티드 | 무스카린 제제로서 벤즈이미다졸리디논 유도체 |
AU2003281200A1 (en) | 2002-07-03 | 2004-01-23 | Tasuku Honjo | Immunopotentiating compositions |
CA2508660C (en) | 2002-12-23 | 2013-08-20 | Wyeth | Antibodies against pd-1 and uses therefor |
AU2003295158A1 (en) * | 2002-12-24 | 2004-07-22 | Biofocus Plc | Compound libraries of 1,3,5-substitute indazole derivatives as compounds for targetting compounds capable of binding to the g-protein coupled receptor |
EP2270051B1 (en) | 2003-01-23 | 2019-05-15 | Ono Pharmaceutical Co., Ltd. | Antibody specific for human PD-1 and CD3 |
NZ563193A (en) | 2005-05-09 | 2010-05-28 | Ono Pharmaceutical Co | Human monoclonal antibodies to programmed death 1(PD-1) and methods for treating cancer using anti-PD-1 antibodies alone or in combination with other immunotherapeutics |
SI1907424T1 (sl) | 2005-07-01 | 2015-12-31 | E. R. Squibb & Sons, L.L.C. | Humana monoklonska protitelesa proti programiranem smrtnem ligandu 1 (PD-L1) |
ES2437327T3 (es) | 2007-06-18 | 2014-01-10 | Merck Sharp & Dohme B.V. | Anticuerpos para el receptor PD-1 humano de muerte programada |
EP2262837A4 (en) | 2008-03-12 | 2011-04-06 | Merck Sharp & Dohme | PD-1 BINDING PROTEINS |
US20110159023A1 (en) | 2008-08-25 | 2011-06-30 | Solomon Langermann | Pd-1 antagonists and methods for treating infectious disease |
SI2342226T1 (sl) | 2008-09-26 | 2016-11-30 | Dana-Farber Cancer Institute Inc. | Humana protitelesa proti PD-1, PD-L1 in PD-L2 in njihove uporabe |
CN114835812A (zh) | 2008-12-09 | 2022-08-02 | 霍夫曼-拉罗奇有限公司 | 抗-pd-l1抗体及它们用于增强t细胞功能的用途 |
JP2013512251A (ja) | 2009-11-24 | 2013-04-11 | アンプリミューン、インコーポレーテッド | Pd−l1/pd−l2の同時阻害 |
BR112014002353B1 (pt) | 2011-08-01 | 2022-09-27 | Genentech, Inc | Usos de antagonistas de ligação do eixo pd-1 e inibidores de mek, composições farmacêuticas, e kit |
US10420761B2 (en) * | 2013-03-15 | 2019-09-24 | University Of Florida Research Foundation, Inc. | Allosteric inhibitors of thymidylate synthase |
WO2019185907A1 (en) * | 2018-03-29 | 2019-10-03 | Universite Paris Est Creteil Val De Marne | Phenylalanine derivatives for use in the treatment of cancers |
-
2021
- 2021-05-04 MX MX2022013843A patent/MX2022013843A/es unknown
- 2021-05-04 BR BR112022022452-4A patent/BR112022022452B1/pt active IP Right Grant
- 2021-05-04 IL IL297781A patent/IL297781A/en unknown
- 2021-05-04 TW TW110116037A patent/TW202202493A/zh unknown
- 2021-05-04 AU AU2021268614A patent/AU2021268614A1/en active Pending
- 2021-05-04 CA CA3177442A patent/CA3177442A1/en active Pending
- 2021-05-04 WO PCT/US2021/030541 patent/WO2021226003A1/en active Application Filing
- 2021-05-04 EP EP21727713.6A patent/EP4146644A1/en active Pending
- 2021-05-04 US US17/920,850 patent/US20230183214A1/en active Pending
- 2021-05-04 AR ARP210101215A patent/AR122007A1/es unknown
- 2021-05-04 KR KR1020227042405A patent/KR20230006898A/ko active Search and Examination
- 2021-05-04 PE PE2022002573A patent/PE20230680A1/es unknown
- 2021-05-04 CR CR20220565A patent/CR20220565A/es unknown
- 2021-05-04 CN CN202180048408.4A patent/CN115836054A/zh active Pending
- 2021-05-04 JP JP2022567075A patent/JP7311720B2/ja active Active
-
2022
- 2022-11-03 CL CL2022003039A patent/CL2022003039A1/es unknown
- 2022-11-04 ZA ZA2022/12095A patent/ZA202212095B/en unknown
- 2022-11-11 CO CONC2022/0016153A patent/CO2022016153A2/es unknown
- 2022-11-21 EC ECSENADI202289498A patent/ECSP22089498A/es unknown
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006048727A1 (en) | 2004-11-02 | 2006-05-11 | Pfizer Products Inc. | Piperazinylphenalkyl lactam/amine ligands for the 5ht1b receptor |
JP2010507664A (ja) | 2006-10-25 | 2010-03-11 | 武田薬品工業株式会社 | ベンズイミダゾール化合物 |
US20190177338A1 (en) | 2017-12-08 | 2019-06-13 | Astrazeneca Ab | Chemical compounds |
Non-Patent Citations (6)
Title |
---|
CAS REGISTRY No.1895984-76-5、1894202-28-8、1893168-18-7、1893051-64-3,DATABASE REGISTRY, [online],2016年,[2023.03.27検索],Retrieved from :STN |
ERMANN, M. et al.,"Use of polymer supported thiophenol for the synthesis and purification of a benzimidazol-2-one library",Tetrahedron Letters,2000年04月,Vol. 41, No. 14,pp. 2483-2485,DOI: 10.1016/S0040-4039(00)00185-4 |
KUMAR, S. et al.,"QSAR modeling of the inhibition of reverse transcriptase enzyme with benzimidazolone analogs",Medicinal Chemistry Research,2010年08月19日,Vol. 20, No. 9,pp. 1530-1541,DOI: 10.1007/s00044-010-9406-2 |
MEANWELL, N.A. et al.,"Regiospecific Functionalization of 1,3-Dihydro-2H-benzimidazol-2-one and Structurally Related Cyclic Urea Derivatives",The Journal of Organic Chemistry,1995年03月,Vol. 60, No. 6,pp. 1565-1582,DOI: 10.1021/jo00111a014 |
OH, S. et al.,"Synthesis and biological evaluation of 2,3-dihydroimidazo[1,2-a]benzimidazole derivatives against Leishmania donovani and Trypanosoma cruzi",European Journal of Medicinal Chemistry,2014年09月,Vol. 84,pp. 395-403,DOI: 10.1016/j.ejmech.2014.07.038 |
ROSSI, A. et al.,"Benzimidazol-Derivate und verwandte Heterocyclen. IV Die Kondensation von o-Phenylendiamin mit α-Aryl- und γ-Aryl-acetessigester",Helvetica Chimica Acta,1960年,Vol. 43, No. 4,pp. 1046-1056,DOI: 10.1002/hlca.19600430413 |
Also Published As
Publication number | Publication date |
---|---|
CR20220565A (es) | 2023-01-13 |
IL297781A (en) | 2022-12-01 |
WO2021226003A1 (en) | 2021-11-11 |
BR112022022452A2 (pt) | 2023-01-10 |
JP2023515721A (ja) | 2023-04-13 |
KR20230006898A (ko) | 2023-01-11 |
US20230183214A1 (en) | 2023-06-15 |
TW202202493A (zh) | 2022-01-16 |
MX2022013843A (es) | 2022-11-30 |
CA3177442A1 (en) | 2021-11-11 |
PE20230680A1 (es) | 2023-04-21 |
BR112022022452B1 (pt) | 2023-11-21 |
ZA202212095B (en) | 2024-04-24 |
AR122007A1 (es) | 2022-08-03 |
CL2022003039A1 (es) | 2023-04-28 |
CO2022016153A2 (es) | 2023-01-26 |
AU2021268614A1 (en) | 2022-12-08 |
ECSP22089498A (es) | 2022-12-30 |
CN115836054A (zh) | 2023-03-21 |
EP4146644A1 (en) | 2023-03-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US10435389B2 (en) | Octahydrocyclopenta[c]pyrrole allosteric inhibitors of SHP2 | |
US11192876B2 (en) | Tricyclic spiro compound | |
JP6299591B2 (ja) | ソマトスタチン受容体作動活性を有する化合物およびその医薬用途 | |
US9586967B2 (en) | Pyrrolo pyrimidine derivative | |
US11065226B2 (en) | Combination comprising EP4 antagonist and immune checkpoint inhibitor | |
US10208034B2 (en) | Quinoline derivative | |
CA3027498A1 (en) | Cxcr4 inhibitors and uses thereof | |
AU2012206561A1 (en) | Novel heterocyclic derivatives and their use in the treatment of neurological disorders | |
US11479550B2 (en) | EP4 antagonist | |
CA3170411A1 (en) | Eif4e inhibitors and uses thereof | |
TW202122382A (zh) | 乙內醯脲衍生物 | |
CA3098335A1 (en) | Antiproliferation compounds and uses thereof | |
TW200831100A (en) | MAPK/ERK kinase inhibitors | |
JP7311720B2 (ja) | Il4i1阻害剤及び使用方法 | |
JP2020515528A (ja) | インドールアミン2,3−ジオキシゲナーゼ(ido)阻害剤としての新規な置換されたn′−ヒドロキシカルバミミドイル−1,2,5−オキサジアゾール化合物 | |
EP4362978A1 (en) | Il4i1 inhibitors and methods of use | |
TW202304887A (zh) | Il4i1抑制劑及其使用方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20221227 Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20230120 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20221227 |
|
A871 | Explanation of circumstances concerning accelerated examination |
Free format text: JAPANESE INTERMEDIATE CODE: A871 Effective date: 20221227 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230404 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20230510 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20230627 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20230706 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7311720 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |