CA3025867A1 - Alpha-d-galactoside inhibitors of galectins - Google Patents

Info

Publication number

CA3025867A1

CA3025867A1 CA3025867A CA3025867A CA3025867A1 CA 3025867 A1 CA3025867 A1 CA 3025867A1 CA 3025867 A CA3025867 A CA 3025867A CA 3025867 A CA3025867 A CA 3025867A CA 3025867 A1 CA3025867 A1 CA 3025867A1

Authority

CA

Canada

Prior art keywords

optionally substituted

deoxy

thio

chloro

galactopyranoside

Prior art date

2016-07-12

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Pending

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 title claims abstract description 17
• 102000007563 Galectins Human genes 0.000 title abstract description 52
• 108010046569 Galectins Proteins 0.000 title abstract description 52
• 239000003112 inhibitor Substances 0.000 title description 34
• 150000001875 compounds Chemical class 0.000 claims abstract description 170
• 108010001517 Galectin 3 Proteins 0.000 claims abstract description 73
• 102000000802 Galectin 3 Human genes 0.000 claims abstract description 70
• 238000000034 method Methods 0.000 claims abstract description 32
• 238000011282 treatment Methods 0.000 claims abstract description 27
• 239000003446 ligand Substances 0.000 claims abstract description 21
• 241000124008 Mammalia Species 0.000 claims abstract description 19
• 150000003214 pyranose derivatives Chemical group 0.000 claims abstract description 5
• -1 D-galactopyranose compound Chemical class 0.000 claims description 146
• 206010028980 Neoplasm Diseases 0.000 claims description 53
• 125000000217 alkyl group Chemical group 0.000 claims description 49
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 40
• 229910052736 halogen Inorganic materials 0.000 claims description 38
• 150000002367 halogens Chemical group 0.000 claims description 38
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 37
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 34
• 229910052801 chlorine Inorganic materials 0.000 claims description 33
• 201000011510 cancer Diseases 0.000 claims description 31
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 31
• 206010016654 Fibrosis Diseases 0.000 claims description 26
• 229910052794 bromium Inorganic materials 0.000 claims description 26
• 230000004761 fibrosis Effects 0.000 claims description 26
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 24
• 208000035475 disorder Diseases 0.000 claims description 23
• 229910052731 fluorine Inorganic materials 0.000 claims description 23
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
• 125000001424 substituent group Chemical group 0.000 claims description 20
• 125000004076 pyridyl group Chemical group 0.000 claims description 19
• 230000033115 angiogenesis Effects 0.000 claims description 17
• 201000010099 disease Diseases 0.000 claims description 17
• 125000001072 heteroaryl group Chemical group 0.000 claims description 17
• 239000008194 pharmaceutical composition Substances 0.000 claims description 17
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 16
• 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 16
• 239000003814 drug Substances 0.000 claims description 16
• 208000030159 metabolic disease Diseases 0.000 claims description 16
• 208000032839 leukemia Diseases 0.000 claims description 13
• 206010061218 Inflammation Diseases 0.000 claims description 12
• 230000004054 inflammatory process Effects 0.000 claims description 12
• 229910052740 iodine Inorganic materials 0.000 claims description 11
• 206010025323 Lymphomas Diseases 0.000 claims description 10
• 229910052739 hydrogen Inorganic materials 0.000 claims description 10
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
• 208000023275 Autoimmune disease Diseases 0.000 claims description 9
• 201000009030 Carcinoma Diseases 0.000 claims description 9
• 206010027406 Mesothelioma Diseases 0.000 claims description 9
• 208000034038 Pathologic Neovascularization Diseases 0.000 claims description 9
• 206010039491 Sarcoma Diseases 0.000 claims description 9
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
• 125000000623 heterocyclic group Chemical group 0.000 claims description 9
• 208000005069 pulmonary fibrosis Diseases 0.000 claims description 9
• 150000003839 salts Chemical class 0.000 claims description 9
• 201000001320 Atherosclerosis Diseases 0.000 claims description 8
• 206010019280 Heart failures Diseases 0.000 claims description 8
• 208000029523 Interstitial Lung disease Diseases 0.000 claims description 8
• 206010040070 Septic Shock Diseases 0.000 claims description 8
• 208000031737 Tissue Adhesions Diseases 0.000 claims description 8
• 230000001594 aberrant effect Effects 0.000 claims description 8
• 125000003118 aryl group Chemical group 0.000 claims description 8
• 208000006673 asthma Diseases 0.000 claims description 8
• 208000030533 eye disease Diseases 0.000 claims description 8
• 208000019622 heart disease Diseases 0.000 claims description 8
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 8
• 208000011379 keloid formation Diseases 0.000 claims description 8
• 208000019423 liver disease Diseases 0.000 claims description 8
• 230000036573 scar formation Effects 0.000 claims description 8
• 230000037390 scarring Effects 0.000 claims description 8
• 230000036303 septic shock Effects 0.000 claims description 8
• 239000012453 solvate Substances 0.000 claims description 8
• 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 7
• 206010009900 Colitis ulcerative Diseases 0.000 claims description 7
• 206010055665 Corneal neovascularisation Diseases 0.000 claims description 7
• 208000011231 Crohn disease Diseases 0.000 claims description 7
• 208000006933 Hermanski-Pudlak Syndrome Diseases 0.000 claims description 7
• 206010071775 Hermansky-Pudlak syndrome Diseases 0.000 claims description 7
• 206010023421 Kidney fibrosis Diseases 0.000 claims description 7
• 206010029113 Neovascularisation Diseases 0.000 claims description 7
• 201000004681 Psoriasis Diseases 0.000 claims description 7
• 206010042971 T-cell lymphoma Diseases 0.000 claims description 7
• 201000006704 Ulcerative Colitis Diseases 0.000 claims description 7
• 206010064930 age-related macular degeneration Diseases 0.000 claims description 7
• 208000019425 cirrhosis of liver Diseases 0.000 claims description 7
• 201000000159 corneal neovascularization Diseases 0.000 claims description 7
• 206010012601 diabetes mellitus Diseases 0.000 claims description 7
• 208000002780 macular degeneration Diseases 0.000 claims description 7
• 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 7
• 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 7
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 7
• 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 7
• 101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 claims description 6
• 125000001624 naphthyl group Chemical group 0.000 claims description 6
• 239000000654 additive Substances 0.000 claims description 5
• 230000000996 additive effect Effects 0.000 claims description 5
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
• 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims description 4
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
• 102100028976 HLA class I histocompatibility antigen, B alpha chain Human genes 0.000 claims description 2
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 3
• 229960003082 galactose Drugs 0.000 abstract description 10
• GZCGUPFRVQAUEE-UHFFFAOYSA-N alpha-D-galactose Natural products OCC(O)C(O)C(O)C(O)C=O GZCGUPFRVQAUEE-UHFFFAOYSA-N 0.000 abstract 1
• WQZGKKKJIJFFOK-UHFFFAOYSA-N alpha-D-glucopyranose Natural products OCC1OC(O)C(O)C(O)C1O WQZGKKKJIJFFOK-UHFFFAOYSA-N 0.000 abstract 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 101
• 239000000203 mixture Substances 0.000 description 84
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 75
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 57
• 239000000243 solution Substances 0.000 description 54
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 50
• 238000005160 1H NMR spectroscopy Methods 0.000 description 44
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 40
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 40
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 38
• 238000006243 chemical reaction Methods 0.000 description 36
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 33
• 239000002904 solvent Substances 0.000 description 32
• 239000000460 chlorine Substances 0.000 description 29
• 238000004440 column chromatography Methods 0.000 description 29
• 239000007787 solid Substances 0.000 description 29
• 229910052938 sodium sulfate Inorganic materials 0.000 description 24
• 235000011152 sodium sulphate Nutrition 0.000 description 24
• 229910021595 Copper(I) iodide Inorganic materials 0.000 description 23
• 101150041968 CDC13 gene Proteins 0.000 description 22
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 22
• 239000012043 crude product Substances 0.000 description 22
• 239000000047 product Substances 0.000 description 22
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
• 239000012267 brine Substances 0.000 description 21
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 21
• WQZGKKKJIJFFOK-SVZMEOIVSA-N (+)-Galactose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-N 0.000 description 19
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
• 108010001498 Galectin 1 Proteins 0.000 description 18
• 102100021736 Galectin-1 Human genes 0.000 description 18
• 239000011541 reaction mixture Substances 0.000 description 18
• LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 17
• 239000012074 organic phase Substances 0.000 description 17
• 150000001720 carbohydrates Chemical class 0.000 description 16
• 239000012071 phase Substances 0.000 description 16
• 239000000377 silicon dioxide Substances 0.000 description 16
• 210000004027 cell Anatomy 0.000 description 15
• 239000008346 aqueous phase Substances 0.000 description 14
• 238000003818 flash chromatography Methods 0.000 description 14
• 238000002953 preparative HPLC Methods 0.000 description 14
• 230000008569 process Effects 0.000 description 14
• 229910052757 nitrogen Inorganic materials 0.000 description 13
• 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 12
• ZXSBDSGRQIWJPM-UHFFFAOYSA-N dimethylcarbamothioic s-acid Chemical compound CN(C)C(S)=O ZXSBDSGRQIWJPM-UHFFFAOYSA-N 0.000 description 12
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 12
• 239000008101 lactose Substances 0.000 description 12
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 10
• 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 10
• 239000007832 Na2SO4 Substances 0.000 description 10
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 10
• 230000000694 effects Effects 0.000 description 10
• 230000003993 interaction Effects 0.000 description 10
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 9
• 230000006870 function Effects 0.000 description 9
• 230000005764 inhibitory process Effects 0.000 description 9
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 8
• 238000004128 high performance liquid chromatography Methods 0.000 description 8
• 239000012442 inert solvent Substances 0.000 description 8
• 229940124597 therapeutic agent Drugs 0.000 description 8
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 7
• KFEUJDWYNGMDBV-LODBTCKLSA-N N-acetyllactosamine Chemical compound O[C@@H]1[C@@H](NC(=O)C)[C@H](O)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 KFEUJDWYNGMDBV-LODBTCKLSA-N 0.000 description 7
• HESSGHHCXGBPAJ-UHFFFAOYSA-N N-acetyllactosamine Natural products CC(=O)NC(C=O)C(O)C(C(O)CO)OC1OC(CO)C(O)C(O)C1O HESSGHHCXGBPAJ-UHFFFAOYSA-N 0.000 description 7
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 7
• USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 7
• 238000001727 in vivo Methods 0.000 description 7
• 210000002540 macrophage Anatomy 0.000 description 7
• UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 7
• 239000000741 silica gel Substances 0.000 description 7
• 229910002027 silica gel Inorganic materials 0.000 description 7
• 229910000104 sodium hydride Inorganic materials 0.000 description 7
• 238000003756 stirring Methods 0.000 description 7
• 239000000126 substance Substances 0.000 description 7
• CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical compound C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 7
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 6
• 206010006187 Breast cancer Diseases 0.000 description 6
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 6
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
• 230000004913 activation Effects 0.000 description 6
• 239000002671 adjuvant Substances 0.000 description 6
• 229910052681 coesite Inorganic materials 0.000 description 6
• 229910052906 cristobalite Inorganic materials 0.000 description 6
• 239000003085 diluting agent Substances 0.000 description 6
• 229930182830 galactose Natural products 0.000 description 6
• 108700039708 galantide Proteins 0.000 description 6
• 230000000670 limiting effect Effects 0.000 description 6
• 239000012299 nitrogen atmosphere Substances 0.000 description 6
• 239000012044 organic layer Substances 0.000 description 6
• 108090000623 proteins and genes Proteins 0.000 description 6
• 102000004169 proteins and genes Human genes 0.000 description 6
• 229910052682 stishovite Inorganic materials 0.000 description 6
• 229910052905 tridymite Inorganic materials 0.000 description 6
• KFEUJDWYNGMDBV-UHFFFAOYSA-N (N-Acetyl)-glucosamin-4-beta-galaktosid Natural products OC1C(NC(=O)C)C(O)OC(CO)C1OC1C(O)C(O)C(O)C(CO)O1 KFEUJDWYNGMDBV-UHFFFAOYSA-N 0.000 description 5
• NWCYIFOZQJOJMW-UHFFFAOYSA-N 2-(4-chloro-3,5-difluorophenyl)ethynyl-trimethylsilane Chemical compound ClC1=C(C=C(C=C1F)C#C[Si](C)(C)C)F NWCYIFOZQJOJMW-UHFFFAOYSA-N 0.000 description 5
• 206010027476 Metastases Diseases 0.000 description 5
• 241001465754 Metazoa Species 0.000 description 5
• 241000699670 Mus sp. Species 0.000 description 5
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
• 230000001154 acute effect Effects 0.000 description 5
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 5
• 238000003556 assay Methods 0.000 description 5
• 230000004069 differentiation Effects 0.000 description 5
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 5
• 125000005842 heteroatom Chemical group 0.000 description 5
• 239000000543 intermediate Substances 0.000 description 5
• 230000009401 metastasis Effects 0.000 description 5
• 230000037361 pathway Effects 0.000 description 5
• 125000006239 protecting group Chemical group 0.000 description 5
• 238000001959 radiotherapy Methods 0.000 description 5
• 238000010992 reflux Methods 0.000 description 5
• 235000012239 silicon dioxide Nutrition 0.000 description 5
• 229910052717 sulfur Inorganic materials 0.000 description 5
• SYKYBMOFPMXDRQ-SOIZYFOBSA-N thiodigalactoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1S[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](CO)O1 SYKYBMOFPMXDRQ-SOIZYFOBSA-N 0.000 description 5
• 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 4
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 4
• 208000026310 Breast neoplasm Diseases 0.000 description 4
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 4
• 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 4
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 4
• 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 description 4
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 4
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
• 238000005481 NMR spectroscopy Methods 0.000 description 4
• 206010060862 Prostate cancer Diseases 0.000 description 4
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 4
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
• 208000005718 Stomach Neoplasms Diseases 0.000 description 4
• 210000001744 T-lymphocyte Anatomy 0.000 description 4
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
• 150000001413 amino acids Chemical class 0.000 description 4
• 235000012538 ammonium bicarbonate Nutrition 0.000 description 4
• 230000033228 biological regulation Effects 0.000 description 4
• 230000015572 biosynthetic process Effects 0.000 description 4
• YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].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 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 4
• 125000004432 carbon atom Chemical group C* 0.000 description 4
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 4
• 229960002949 fluorouracil Drugs 0.000 description 4
• 206010017758 gastric cancer Diseases 0.000 description 4
• 230000014509 gene expression Effects 0.000 description 4
• 210000002865 immune cell Anatomy 0.000 description 4
• 230000003308 immunostimulating effect Effects 0.000 description 4
• 238000005259 measurement Methods 0.000 description 4
• 210000000651 myofibroblast Anatomy 0.000 description 4
• 239000003921 oil Substances 0.000 description 4
• 201000011549 stomach cancer Diseases 0.000 description 4
• 230000001225 therapeutic effect Effects 0.000 description 4
• AAGYWTCZOUXEDH-UHFFFAOYSA-N 3-bromo-5-chloropyridine-2-carbonitrile Chemical compound ClC1=CN=C(C#N)C(Br)=C1 AAGYWTCZOUXEDH-UHFFFAOYSA-N 0.000 description 3
• VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
• 102100039558 Galectin-3 Human genes 0.000 description 3
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 3
• BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 3
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
• 208000024770 Thyroid neoplasm Diseases 0.000 description 3
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 3
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 3
• 230000001093 anti-cancer Effects 0.000 description 3
• 230000003510 anti-fibrotic effect Effects 0.000 description 3
• 239000002246 antineoplastic agent Substances 0.000 description 3
• 230000006907 apoptotic process Effects 0.000 description 3
• 235000014633 carbohydrates Nutrition 0.000 description 3
• 239000000969 carrier Substances 0.000 description 3
• 230000021164 cell adhesion Effects 0.000 description 3
• 238000002648 combination therapy Methods 0.000 description 3
• 210000000172 cytosol Anatomy 0.000 description 3
• 229940127089 cytotoxic agent Drugs 0.000 description 3
• 229940043279 diisopropylamine Drugs 0.000 description 3
• 238000002875 fluorescence polarization Methods 0.000 description 3
• VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 description 3
• 235000008191 folinic acid Nutrition 0.000 description 3
• 239000011672 folinic acid Substances 0.000 description 3
• 125000000524 functional group Chemical group 0.000 description 3
• 208000005017 glioblastoma Diseases 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• 102000006639 indoleamine 2,3-dioxygenase Human genes 0.000 description 3
• 108020004201 indoleamine 2,3-dioxygenase Proteins 0.000 description 3
• 230000006698 induction Effects 0.000 description 3
• 239000002523 lectin Substances 0.000 description 3
• 229960001691 leucovorin Drugs 0.000 description 3
• PHWISQNXPLXQRU-UHFFFAOYSA-N n,n-dimethylcarbamothioyl chloride Chemical compound CN(C)C(Cl)=S PHWISQNXPLXQRU-UHFFFAOYSA-N 0.000 description 3
• 210000000440 neutrophil Anatomy 0.000 description 3
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 3
• 230000003389 potentiating effect Effects 0.000 description 3
• 102000005962 receptors Human genes 0.000 description 3
• 108020003175 receptors Proteins 0.000 description 3
• 230000002829 reductive effect Effects 0.000 description 3
• 230000004044 response Effects 0.000 description 3
• 238000012552 review Methods 0.000 description 3
• 229910000077 silane Inorganic materials 0.000 description 3
• 239000012312 sodium hydride Substances 0.000 description 3
• 239000011593 sulfur Substances 0.000 description 3
• 208000024891 symptom Diseases 0.000 description 3
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 3
• 201000002510 thyroid cancer Diseases 0.000 description 3
• 210000001519 tissue Anatomy 0.000 description 3
• 210000004881 tumor cell Anatomy 0.000 description 3
• YXTKHLHCVFUPPT-YYFJYKOTSA-N (2s)-2-[[4-[(2-amino-5-formyl-4-oxo-1,6,7,8-tetrahydropteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid;(1r,2r)-1,2-dimethanidylcyclohexane;5-fluoro-1h-pyrimidine-2,4-dione;oxalic acid;platinum(2+) Chemical compound [Pt+2].OC(=O)C(O)=O.[CH2-][C@@H]1CCCC[C@H]1[CH2-].FC1=CNC(=O)NC1=O.C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 YXTKHLHCVFUPPT-YYFJYKOTSA-N 0.000 description 2
• NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 2
• PYMYPHUHKUWMLA-UHFFFAOYSA-N 2,3,4,5-tetrahydroxypentanal Chemical compound OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 2
• HEPDEDXHPLWMMX-UHFFFAOYSA-N 2,6-difluoro-4-(2-trimethylsilylethynyl)benzonitrile Chemical compound FC1=C(C#N)C(=CC(=C1)C#C[Si](C)(C)C)F HEPDEDXHPLWMMX-UHFFFAOYSA-N 0.000 description 2
• MMDZGXFBNJYFID-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)ethynyl-trimethylsilane Chemical compound C[Si](C)(C)C#CC1=CC=C(Cl)C(Cl)=C1 MMDZGXFBNJYFID-UHFFFAOYSA-N 0.000 description 2
• NAMUZWXILOMIGX-UHFFFAOYSA-N 2-(5-chloropyridin-3-yl)ethynyl-trimethylsilane Chemical compound C[Si](C)(C)C#CC1=CN=CC(Cl)=C1 NAMUZWXILOMIGX-UHFFFAOYSA-N 0.000 description 2
• YLPHXFCHWDGOOT-UHFFFAOYSA-N 2-(5-fluoropyridin-3-yl)ethynyl-trimethylsilane Chemical compound C[Si](C)(C)C#CC1=CN=CC(F)=C1 YLPHXFCHWDGOOT-UHFFFAOYSA-N 0.000 description 2
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
• BMWOENOCPPYRRS-UHFFFAOYSA-N 4-bromo-2-chloro-6-fluoroaniline Chemical compound NC1=C(F)C=C(Br)C=C1Cl BMWOENOCPPYRRS-UHFFFAOYSA-N 0.000 description 2
• DWPSVLFVEMJREE-UHFFFAOYSA-N 4-chloro-1h-pyridine-2-thione Chemical compound SC1=CC(Cl)=CC=N1 DWPSVLFVEMJREE-UHFFFAOYSA-N 0.000 description 2
• NWRZTOGDTNCJHP-UHFFFAOYSA-N 5-bromo-1,2-dichloro-3-fluorobenzene Chemical compound FC1=CC(Br)=CC(Cl)=C1Cl NWRZTOGDTNCJHP-UHFFFAOYSA-N 0.000 description 2
• UJCHMLGLJPCYHU-UHFFFAOYSA-N 5-chloropyridine-3-thiol Chemical compound SC1=CN=CC(Cl)=C1 UJCHMLGLJPCYHU-UHFFFAOYSA-N 0.000 description 2
• ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 2
• 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 2
• 201000003076 Angiosarcoma Diseases 0.000 description 2
• BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
• 206010003571 Astrocytoma Diseases 0.000 description 2
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 2
• 108010074708 B7-H1 Antigen Proteins 0.000 description 2
• 206010004146 Basal cell carcinoma Diseases 0.000 description 2
• 206010004593 Bile duct cancer Diseases 0.000 description 2
• 206010005003 Bladder cancer Diseases 0.000 description 2
• 208000003174 Brain Neoplasms Diseases 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• 208000011691 Burkitt lymphomas Diseases 0.000 description 2
• 206010008342 Cervix carcinoma Diseases 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• 208000005243 Chondrosarcoma Diseases 0.000 description 2
• 201000009047 Chordoma Diseases 0.000 description 2
• 208000006332 Choriocarcinoma Diseases 0.000 description 2
• 206010009944 Colon cancer Diseases 0.000 description 2
• 208000009798 Craniopharyngioma Diseases 0.000 description 2
• 102000004127 Cytokines Human genes 0.000 description 2
• 108090000695 Cytokines Proteins 0.000 description 2
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 201000009051 Embryonal Carcinoma Diseases 0.000 description 2
• 206010014733 Endometrial cancer Diseases 0.000 description 2
• 206010014759 Endometrial neoplasm Diseases 0.000 description 2
• 206010014967 Ependymoma Diseases 0.000 description 2
• 208000000461 Esophageal Neoplasms Diseases 0.000 description 2
• 208000006168 Ewing Sarcoma Diseases 0.000 description 2
• 201000008808 Fibrosarcoma Diseases 0.000 description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• 229940126043 Galectin-3 inhibitor Drugs 0.000 description 2
• 208000032612 Glial tumor Diseases 0.000 description 2
• 206010018338 Glioma Diseases 0.000 description 2
• 108090000288 Glycoproteins Proteins 0.000 description 2
• 102000003886 Glycoproteins Human genes 0.000 description 2
• 208000001258 Hemangiosarcoma Diseases 0.000 description 2
• 208000017604 Hodgkin disease Diseases 0.000 description 2
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 2
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
• 229940076838 Immune checkpoint inhibitor Drugs 0.000 description 2
• 108010002350 Interleukin-2 Proteins 0.000 description 2
• 102000000588 Interleukin-2 Human genes 0.000 description 2
• 206010023825 Laryngeal cancer Diseases 0.000 description 2
• 102000004856 Lectins Human genes 0.000 description 2
• 108090001090 Lectins Proteins 0.000 description 2
• 208000018142 Leiomyosarcoma Diseases 0.000 description 2
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 2
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
• 208000007054 Medullary Carcinoma Diseases 0.000 description 2
• 208000000172 Medulloblastoma Diseases 0.000 description 2
• 208000003445 Mouth Neoplasms Diseases 0.000 description 2
• 208000034578 Multiple myelomas Diseases 0.000 description 2
• 241000699666 Mus <mouse, genus> Species 0.000 description 2
• 208000034176 Neoplasms, Germ Cell and Embryonal Diseases 0.000 description 2
• 206010029260 Neuroblastoma Diseases 0.000 description 2
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 2
• 206010030155 Oesophageal carcinoma Diseases 0.000 description 2
• 201000010133 Oligodendroglioma Diseases 0.000 description 2
• 206010033128 Ovarian cancer Diseases 0.000 description 2
• 206010061535 Ovarian neoplasm Diseases 0.000 description 2
• 101710195703 Oxygen-dependent coproporphyrinogen-III oxidase Proteins 0.000 description 2
• 102100036201 Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial Human genes 0.000 description 2
• 101710200437 Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial Proteins 0.000 description 2
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
• 208000007641 Pinealoma Diseases 0.000 description 2
• 206010035226 Plasma cell myeloma Diseases 0.000 description 2
• 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 description 2
• 208000033759 Prolymphocytic T-Cell Leukemia Diseases 0.000 description 2
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
• 208000015634 Rectal Neoplasms Diseases 0.000 description 2
• 208000006265 Renal cell carcinoma Diseases 0.000 description 2
• 201000000582 Retinoblastoma Diseases 0.000 description 2
• 201000010208 Seminoma Diseases 0.000 description 2
• 208000000453 Skin Neoplasms Diseases 0.000 description 2
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
• 208000026651 T-cell prolymphocytic leukemia Diseases 0.000 description 2
• 208000024313 Testicular Neoplasms Diseases 0.000 description 2
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
• 108010083111 Ubiquitin-Protein Ligases Proteins 0.000 description 2
• 102000006275 Ubiquitin-Protein Ligases Human genes 0.000 description 2
• 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 2
• 208000002495 Uterine Neoplasms Diseases 0.000 description 2
• 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 2
• 208000008383 Wilms tumor Diseases 0.000 description 2
• LUTSRLYCMSCGCS-BWOMAWGNSA-N [(3s,8r,9s,10r,13s)-10,13-dimethyl-17-oxo-1,2,3,4,7,8,9,11,12,16-decahydrocyclopenta[a]phenanthren-3-yl] acetate Chemical compound C([C@@H]12)C[C@]3(C)C(=O)CC=C3[C@@H]1CC=C1[C@]2(C)CC[C@H](OC(=O)C)C1 LUTSRLYCMSCGCS-BWOMAWGNSA-N 0.000 description 2
• WLLIXJBWWFGEHT-UHFFFAOYSA-N [tert-butyl(dimethyl)silyl] trifluoromethanesulfonate Chemical compound CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F WLLIXJBWWFGEHT-UHFFFAOYSA-N 0.000 description 2
• 229960001138 acetylsalicylic acid Drugs 0.000 description 2
• 239000002253 acid Substances 0.000 description 2
• 238000005903 acid hydrolysis reaction Methods 0.000 description 2
• 208000017733 acquired polycythemia vera Diseases 0.000 description 2
• 208000009956 adenocarcinoma Diseases 0.000 description 2
• 239000001099 ammonium carbonate Substances 0.000 description 2
• 238000004458 analytical method Methods 0.000 description 2
• 230000000118 anti-neoplastic effect Effects 0.000 description 2
• 210000003719 b-lymphocyte Anatomy 0.000 description 2
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
• 201000007180 bile duct carcinoma Diseases 0.000 description 2
• 201000001531 bladder carcinoma Diseases 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• 208000003362 bronchogenic carcinoma Diseases 0.000 description 2
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
• 201000010881 cervical cancer Diseases 0.000 description 2
• 230000008859 change Effects 0.000 description 2
• 239000003795 chemical substances by application Substances 0.000 description 2
• 239000012320 chlorinating reagent Substances 0.000 description 2
• 238000004587 chromatography analysis Methods 0.000 description 2
• 125000006165 cyclic alkyl group Chemical group 0.000 description 2
• 125000004122 cyclic group Chemical group 0.000 description 2
• 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 2
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• 230000001086 cytosolic effect Effects 0.000 description 2
• 230000006378 damage Effects 0.000 description 2
• 230000007423 decrease Effects 0.000 description 2
• 238000001212 derivatisation Methods 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• 230000018109 developmental process Effects 0.000 description 2
• 150000002016 disaccharides Chemical class 0.000 description 2
• 229940079593 drug Drugs 0.000 description 2
• 229940000406 drug candidate Drugs 0.000 description 2
• 238000010828 elution Methods 0.000 description 2
• 208000037828 epithelial carcinoma Diseases 0.000 description 2
• 201000004101 esophageal cancer Diseases 0.000 description 2
• 229940093499 ethyl acetate Drugs 0.000 description 2
• 235000019439 ethyl acetate Nutrition 0.000 description 2
• 238000000605 extraction Methods 0.000 description 2
• 239000011737 fluorine Substances 0.000 description 2
• 210000001035 gastrointestinal tract Anatomy 0.000 description 2
• 229920000550 glycopolymer Polymers 0.000 description 2
• 201000009277 hairy cell leukemia Diseases 0.000 description 2
• 201000010536 head and neck cancer Diseases 0.000 description 2
• 208000014829 head and neck neoplasm Diseases 0.000 description 2
• 208000025750 heavy chain disease Diseases 0.000 description 2
• 201000002222 hemangioblastoma Diseases 0.000 description 2
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
• 239000012274 immune-checkpoint protein inhibitor Substances 0.000 description 2
• 230000002401 inhibitory effect Effects 0.000 description 2
• 239000003456 ion exchange resin Substances 0.000 description 2
• 229920003303 ion-exchange polymer Polymers 0.000 description 2
• 229960004768 irinotecan Drugs 0.000 description 2
• UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 2
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
• 206010023841 laryngeal neoplasm Diseases 0.000 description 2
• GOTYRUGSSMKFNF-UHFFFAOYSA-N lenalidomide Chemical compound C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O GOTYRUGSSMKFNF-UHFFFAOYSA-N 0.000 description 2
• 206010024627 liposarcoma Diseases 0.000 description 2
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
• 201000007270 liver cancer Diseases 0.000 description 2
• 208000014018 liver neoplasm Diseases 0.000 description 2
• 210000004072 lung Anatomy 0.000 description 2
• 201000005296 lung carcinoma Diseases 0.000 description 2
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 2
• 238000004519 manufacturing process Methods 0.000 description 2
• 239000000463 material Substances 0.000 description 2
• 239000011159 matrix material Substances 0.000 description 2
• 208000023356 medullary thyroid gland carcinoma Diseases 0.000 description 2
• 201000001441 melanoma Diseases 0.000 description 2
• 206010027191 meningioma Diseases 0.000 description 2
• MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• 125000002950 monocyclic group Chemical group 0.000 description 2
• 239000000178 monomer Substances 0.000 description 2
• 238000010172 mouse model Methods 0.000 description 2
• 208000001611 myxosarcoma Diseases 0.000 description 2
• 208000025189 neoplasm of testis Diseases 0.000 description 2
• 208000007538 neurilemmoma Diseases 0.000 description 2
• 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
• 239000012038 nucleophile Substances 0.000 description 2
• 201000008968 osteosarcoma Diseases 0.000 description 2
• DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 2
• 229960001756 oxaliplatin Drugs 0.000 description 2
• AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 2
• 201000002528 pancreatic cancer Diseases 0.000 description 2
• 208000008443 pancreatic carcinoma Diseases 0.000 description 2
• 208000004019 papillary adenocarcinoma Diseases 0.000 description 2
• 201000010198 papillary carcinoma Diseases 0.000 description 2
• 208000024724 pineal body neoplasm Diseases 0.000 description 2
• 201000004123 pineal gland cancer Diseases 0.000 description 2
• 229920001467 poly(styrenesulfonates) Polymers 0.000 description 2
• 208000037244 polycythemia vera Diseases 0.000 description 2
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
• 239000000843 powder Substances 0.000 description 2
• 238000012746 preparative thin layer chromatography Methods 0.000 description 2
• 125000005494 pyridonyl group Chemical group 0.000 description 2
• 206010038038 rectal cancer Diseases 0.000 description 2
• 201000001275 rectum cancer Diseases 0.000 description 2
• 230000001105 regulatory effect Effects 0.000 description 2
• 201000009410 rhabdomyosarcoma Diseases 0.000 description 2
• 125000006413 ring segment Chemical group 0.000 description 2
• 239000000523 sample Substances 0.000 description 2
• 201000008407 sebaceous adenocarcinoma Diseases 0.000 description 2
• 230000035945 sensitivity Effects 0.000 description 2
• 230000011664 signaling Effects 0.000 description 2
• 208000000587 small cell lung carcinoma Diseases 0.000 description 2
• 150000003384 small molecules Chemical class 0.000 description 2
• 238000001228 spectrum Methods 0.000 description 2
• 206010041823 squamous cell carcinoma Diseases 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• 210000002784 stomach Anatomy 0.000 description 2
• 239000000725 suspension Substances 0.000 description 2
• 201000010965 sweat gland carcinoma Diseases 0.000 description 2
• 206010042863 synovial sarcoma Diseases 0.000 description 2
• 238000003786 synthesis reaction Methods 0.000 description 2
• 230000008685 targeting Effects 0.000 description 2
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 2
• 239000012414 tert-butyl nitrite Substances 0.000 description 2
• 201000003120 testicular cancer Diseases 0.000 description 2
• 238000012360 testing method Methods 0.000 description 2
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 2
• 125000001544 thienyl group Chemical group 0.000 description 2
• 230000002992 thymic effect Effects 0.000 description 2
• DXYJNFXSJYLMKH-UHFFFAOYSA-N trimethyl-[2-(3,4,5-trifluorophenyl)ethynyl]silane Chemical compound C[Si](C)(C)C#CC1=CC(F)=C(F)C(F)=C1 DXYJNFXSJYLMKH-UHFFFAOYSA-N 0.000 description 2
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• 230000004614 tumor growth Effects 0.000 description 2
• 208000010570 urinary bladder carcinoma Diseases 0.000 description 2
• 230000002485 urinary effect Effects 0.000 description 2
• GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 1
• FMCAFXHLMUOIGG-JTJHWIPRSA-N (2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-JTJHWIPRSA-N 0.000 description 1
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 1
• 125000001607 1,2,3-triazol-1-yl group Chemical group [*]N1N=NC([H])=C1[H] 0.000 description 1
• VILFTWLXLYIEMV-UHFFFAOYSA-N 1,5-difluoro-2,4-dinitrobenzene Chemical compound [O-][N+](=O)C1=CC([N+]([O-])=O)=C(F)C=C1F VILFTWLXLYIEMV-UHFFFAOYSA-N 0.000 description 1
• GQBRZBHEPUQRPL-LJQANCHMSA-N 1-[4-[4-[3-methyl-4-[[(1r)-1-phenylethoxy]carbonylamino]-1,2-oxazol-5-yl]phenyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound O([C@H](C)C=1C=CC=CC=1)C(=O)NC=1C(C)=NOC=1C(C=C1)=CC=C1C(C=C1)=CC=C1C1(C(O)=O)CC1 GQBRZBHEPUQRPL-LJQANCHMSA-N 0.000 description 1
• UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
• 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 description 1
• VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
• JYWKEVKEKOTYEX-UHFFFAOYSA-N 2,6-dibromo-4-chloroiminocyclohexa-2,5-dien-1-one Chemical compound ClN=C1C=C(Br)C(=O)C(Br)=C1 JYWKEVKEKOTYEX-UHFFFAOYSA-N 0.000 description 1
• YRZSWNDTZJMJKZ-UHFFFAOYSA-N 2-(3,4-dichloro-5-fluorophenyl)ethynyl-trimethylsilane Chemical compound ClC=1C=C(C=C(C=1Cl)F)C#C[Si](C)(C)C YRZSWNDTZJMJKZ-UHFFFAOYSA-N 0.000 description 1
• BOTQKHYXZUDZII-UHFFFAOYSA-N 2-(3,5-difluoro-4-methylphenyl)ethynyl-trimethylsilane Chemical compound FC=1C=C(C=C(C=1C)F)C#C[Si](C)(C)C BOTQKHYXZUDZII-UHFFFAOYSA-N 0.000 description 1
• WJNQGGOKAVIPOU-UHFFFAOYSA-N 2-(4-bromo-3,5-difluorophenyl)ethynyl-trimethylsilane Chemical compound BrC1=C(F)C=C(C#C[Si](C)(C)C)C=C1F WJNQGGOKAVIPOU-UHFFFAOYSA-N 0.000 description 1
• NMUSOBSFMROWTH-UHFFFAOYSA-N 2-(4-bromo-3-fluorophenyl)ethynyl-trimethylsilane Chemical compound C[Si](C)(C)C#CC1=CC=C(Br)C(F)=C1 NMUSOBSFMROWTH-UHFFFAOYSA-N 0.000 description 1
• FHDIHDDKMQTIFS-UHFFFAOYSA-N 2-(4-chloro-3-fluorophenyl)ethynyl-trimethylsilane Chemical compound ClC1=C(C=C(C=C1)C#C[Si](C)(C)C)F FHDIHDDKMQTIFS-UHFFFAOYSA-N 0.000 description 1
• OYSQEVSFCULSFM-UHFFFAOYSA-N 2-[3,5-difluoro-4-(trifluoromethyl)phenyl]ethynyl-trimethylsilane Chemical compound FC=1C=C(C=C(C=1C(F)(F)F)F)C#C[Si](C)(C)C OYSQEVSFCULSFM-UHFFFAOYSA-N 0.000 description 1
• WOLGNRYEQPISPB-UHFFFAOYSA-N 2-bromo-1,3-difluoro-5-iodobenzene Chemical compound FC1=CC(I)=CC(F)=C1Br WOLGNRYEQPISPB-UHFFFAOYSA-N 0.000 description 1
• FGSAQRJRWCZLOB-UHFFFAOYSA-N 2-chloro-4-fluoropyridine Chemical compound FC1=CC=NC(Cl)=C1 FGSAQRJRWCZLOB-UHFFFAOYSA-N 0.000 description 1
• 125000005916 2-methylpentyl group Chemical group 0.000 description 1
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
• MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
• HNJZDPKMMZXSKT-UHFFFAOYSA-N 3,4-dichlorobenzenethiol Chemical compound SC1=CC=C(Cl)C(Cl)=C1 HNJZDPKMMZXSKT-UHFFFAOYSA-N 0.000 description 1
• NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 1
• QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 1
• BELDOPUBSLPBCQ-UHFFFAOYSA-N 3-bromo-5-chloropyridine Chemical compound ClC1=CN=CC(Br)=C1 BELDOPUBSLPBCQ-UHFFFAOYSA-N 0.000 description 1
• HNNNBQRRIHKFLI-UHFFFAOYSA-N 3-bromo-5-fluoropyridine Chemical compound FC1=CN=CC(Br)=C1 HNNNBQRRIHKFLI-UHFFFAOYSA-N 0.000 description 1
• SUISJFAATFTCRL-UHFFFAOYSA-N 3-bromo-5-methoxybenzenethiol Chemical compound COC1=CC(S)=CC(Br)=C1 SUISJFAATFTCRL-UHFFFAOYSA-N 0.000 description 1
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
• AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 1
• VNRGFXKFARXGSX-UHFFFAOYSA-N 4,6-dichloropyridine-3-carbonitrile Chemical compound ClC1=CC(Cl)=C(C#N)C=N1 VNRGFXKFARXGSX-UHFFFAOYSA-N 0.000 description 1
• CFPZDVAZISWERM-UHFFFAOYSA-N 4-bromo-1,2-dichlorobenzene Chemical compound ClC1=CC=C(Br)C=C1Cl CFPZDVAZISWERM-UHFFFAOYSA-N 0.000 description 1
• AGYWDGVTLKNTBS-UHFFFAOYSA-N 4-bromo-1-chloro-2-fluorobenzene Chemical compound FC1=CC(Br)=CC=C1Cl AGYWDGVTLKNTBS-UHFFFAOYSA-N 0.000 description 1
• TZHQWUAOIWRFSW-UHFFFAOYSA-N 4-bromo-2,6-difluorobenzonitrile Chemical compound FC1=CC(Br)=CC(F)=C1C#N TZHQWUAOIWRFSW-UHFFFAOYSA-N 0.000 description 1
• GZRMNMGWNKSANY-UHFFFAOYSA-N 4-bromo-2-fluoroaniline Chemical compound NC1=CC=C(Br)C=C1F GZRMNMGWNKSANY-UHFFFAOYSA-N 0.000 description 1
• OZUXGFRLSKQVMI-UHFFFAOYSA-N 4-chloro-1h-pyridin-2-one Chemical compound OC1=CC(Cl)=CC=N1 OZUXGFRLSKQVMI-UHFFFAOYSA-N 0.000 description 1
• 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 1
• QPJKIRNIIXIPIE-UHFFFAOYSA-N 5-bromo-1,3-difluoro-2-(trifluoromethyl)benzene Chemical compound FC1=CC(Br)=CC(F)=C1C(F)(F)F QPJKIRNIIXIPIE-UHFFFAOYSA-N 0.000 description 1
• NGINOAWMGMGBPJ-UHFFFAOYSA-N 5-bromo-1,3-difluoro-2-methylbenzene Chemical compound CC1=C(F)C=C(Br)C=C1F NGINOAWMGMGBPJ-UHFFFAOYSA-N 0.000 description 1
• SIYPZKHSXDFDRA-UHFFFAOYSA-N 5-bromo-3-chloropyridine-2-carbonitrile Chemical compound ClC1=CC(Br)=CN=C1C#N SIYPZKHSXDFDRA-UHFFFAOYSA-N 0.000 description 1
• VNYBIBSZZDAEOK-UHFFFAOYSA-N 5-bromopyridin-3-ol Chemical compound OC1=CN=CC(Br)=C1 VNYBIBSZZDAEOK-UHFFFAOYSA-N 0.000 description 1
• WTGUVGABIUXMIS-UHFFFAOYSA-N 5-bromopyridine-3-thiol Chemical compound SC1=CN=CC(Br)=C1 WTGUVGABIUXMIS-UHFFFAOYSA-N 0.000 description 1
• TUIDQYRZDZRHPQ-UHFFFAOYSA-N 5-chloropyridin-3-ol Chemical compound OC1=CN=CC(Cl)=C1 TUIDQYRZDZRHPQ-UHFFFAOYSA-N 0.000 description 1
• BZXWRVPVZZZAKB-UHFFFAOYSA-N 5-ethynyl-1,2,3-trifluorobenzene Chemical group FC1=CC(C#C)=CC(F)=C1F BZXWRVPVZZZAKB-UHFFFAOYSA-N 0.000 description 1
• FCSKOFQQCWLGMV-UHFFFAOYSA-N 5-{5-[2-chloro-4-(4,5-dihydro-1,3-oxazol-2-yl)phenoxy]pentyl}-3-methylisoxazole Chemical compound O1N=C(C)C=C1CCCCCOC1=CC=C(C=2OCCN=2)C=C1Cl FCSKOFQQCWLGMV-UHFFFAOYSA-N 0.000 description 1
• WYWHKKSPHMUBEB-UHFFFAOYSA-N 6-Mercaptoguanine Natural products N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 1
• 102100023990 60S ribosomal protein L17 Human genes 0.000 description 1
• STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
• 206010067484 Adverse reaction Diseases 0.000 description 1
• 102000009027 Albumins Human genes 0.000 description 1
• 108010088751 Albumins Proteins 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 102100029822 B- and T-lymphocyte attenuator Human genes 0.000 description 1
• 229910015900 BF3 Inorganic materials 0.000 description 1
• 108010006654 Bleomycin Proteins 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• RFIYZKRKHKXROB-UHFFFAOYSA-N BrC1=CC(=NC=C1C#N)Br Chemical compound BrC1=CC(=NC=C1C#N)Br RFIYZKRKHKXROB-UHFFFAOYSA-N 0.000 description 1
• 108091007381 CBL proteins Proteins 0.000 description 1
• 102100024263 CD160 antigen Human genes 0.000 description 1
• 102100038077 CD226 antigen Human genes 0.000 description 1
• 101150013553 CD40 gene Proteins 0.000 description 1
• 108010062802 CD66 antigens Proteins 0.000 description 1
• 229940045513 CTLA4 antagonist Drugs 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 description 1
• GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 description 1
• 102100024533 Carcinoembryonic antigen-related cell adhesion molecule 1 Human genes 0.000 description 1
• 108010001857 Cell Surface Receptors Proteins 0.000 description 1
• 102000000844 Cell Surface Receptors Human genes 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• 229920000858 Cyclodextrin Polymers 0.000 description 1
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
• UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
• YIIMEMSDCNDGTB-UHFFFAOYSA-N Dimethylcarbamoyl chloride Chemical compound CN(C)C(Cl)=O YIIMEMSDCNDGTB-UHFFFAOYSA-N 0.000 description 1
• 102100035813 E3 ubiquitin-protein ligase CBL Human genes 0.000 description 1
• 102100035273 E3 ubiquitin-protein ligase CBL-B Human genes 0.000 description 1
• 102100034214 E3 ubiquitin-protein ligase RNF128 Human genes 0.000 description 1
• 241000196324 Embryophyta Species 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
• 241000282326 Felis catus Species 0.000 description 1
• 102000020897 Formins Human genes 0.000 description 1
• 108091022623 Formins Proteins 0.000 description 1
• 108010001515 Galectin 4 Proteins 0.000 description 1
• 102000000805 Galectin 4 Human genes 0.000 description 1
• 102000044465 Galectin-7 Human genes 0.000 description 1
• 102100031351 Galectin-9 Human genes 0.000 description 1
• 101710121810 Galectin-9 Proteins 0.000 description 1
• 102100025614 Galectin-related protein Human genes 0.000 description 1
• 102000013382 Gelatinases Human genes 0.000 description 1
• 108010026132 Gelatinases Proteins 0.000 description 1
• 108010015899 Glycopeptides Proteins 0.000 description 1
• 102000002068 Glycopeptides Human genes 0.000 description 1
• 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
• 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
• 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 description 1
• 101000864344 Homo sapiens B- and T-lymphocyte attenuator Proteins 0.000 description 1
• 101000761938 Homo sapiens CD160 antigen Proteins 0.000 description 1
• 101000884298 Homo sapiens CD226 antigen Proteins 0.000 description 1
• 101000737265 Homo sapiens E3 ubiquitin-protein ligase CBL-B Proteins 0.000 description 1
• 101000711673 Homo sapiens E3 ubiquitin-protein ligase RNF128 Proteins 0.000 description 1
• 101000608772 Homo sapiens Galectin-7 Proteins 0.000 description 1
• 101001004750 Homo sapiens Galectin-related protein Proteins 0.000 description 1
• 101001068133 Homo sapiens Hepatitis A virus cellular receptor 2 Proteins 0.000 description 1
• 101000959820 Homo sapiens Interferon alpha-1/13 Proteins 0.000 description 1
• 101001137987 Homo sapiens Lymphocyte activation gene 3 protein Proteins 0.000 description 1
• 101000831007 Homo sapiens T-cell immunoreceptor with Ig and ITIM domains Proteins 0.000 description 1
• 101000596234 Homo sapiens T-cell surface protein tactile Proteins 0.000 description 1
• 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 1
• 101000851370 Homo sapiens Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 description 1
• 101000666896 Homo sapiens V-type immunoglobulin domain-containing suppressor of T-cell activation Proteins 0.000 description 1
• 206010020751 Hypersensitivity Diseases 0.000 description 1
• XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 1
• XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 1
• 102000009438 IgE Receptors Human genes 0.000 description 1
• 108010073816 IgE Receptors Proteins 0.000 description 1
• 241000209621 Ingrassia Species 0.000 description 1
• 102100040019 Interferon alpha-1/13 Human genes 0.000 description 1
• 108010002352 Interleukin-1 Proteins 0.000 description 1
• 108010065805 Interleukin-12 Proteins 0.000 description 1
• 102000013462 Interleukin-12 Human genes 0.000 description 1
• 102000003812 Interleukin-15 Human genes 0.000 description 1
• 108090000172 Interleukin-15 Proteins 0.000 description 1
• 102100030704 Interleukin-21 Human genes 0.000 description 1
• 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 1
• 102000017578 LAG3 Human genes 0.000 description 1
• 102000007547 Laminin Human genes 0.000 description 1
• 108010085895 Laminin Proteins 0.000 description 1
• 239000002841 Lewis acid Substances 0.000 description 1
• 210000004322 M2 macrophage Anatomy 0.000 description 1
• 108010061593 Member 14 Tumor Necrosis Factor Receptors Proteins 0.000 description 1
• 101100407308 Mus musculus Pdcd1lg2 gene Proteins 0.000 description 1
• 108010008211 N-Formylmethionine Leucyl-Phenylalanine Proteins 0.000 description 1
• LVDRREOUMKACNJ-BKMJKUGQSA-N N-[(2R,3S)-2-(4-chlorophenyl)-1-(1,4-dimethyl-2-oxoquinolin-7-yl)-6-oxopiperidin-3-yl]-2-methylpropane-1-sulfonamide Chemical compound CC(C)CS(=O)(=O)N[C@H]1CCC(=O)N([C@@H]1c1ccc(Cl)cc1)c1ccc2c(C)cc(=O)n(C)c2c1 LVDRREOUMKACNJ-BKMJKUGQSA-N 0.000 description 1
• ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
• 101000666903 Naja atra Kunitz-type serine protease inhibitor NACI Proteins 0.000 description 1
• 101150097297 Nedd4 gene Proteins 0.000 description 1
• 108010089484 PRM-151 Proteins 0.000 description 1
• 229930012538 Paclitaxel Natural products 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
• 241000139306 Platt Species 0.000 description 1
• 102100029740 Poliovirus receptor Human genes 0.000 description 1
• 108700030875 Programmed Cell Death 1 Ligand 2 Proteins 0.000 description 1
• 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 description 1
• 101710089372 Programmed cell death protein 1 Proteins 0.000 description 1
• 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
• 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
• 108010076504 Protein Sorting Signals Proteins 0.000 description 1
• 208000003251 Pruritus Diseases 0.000 description 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• 108030001238 RING-type E3 ubiquitin transferases Proteins 0.000 description 1
• 102000034442 RING-type E3 ubiquitin transferases Human genes 0.000 description 1
• 241000282887 Suidae Species 0.000 description 1
• 230000005867 T cell response Effects 0.000 description 1
• 102100024834 T-cell immunoreceptor with Ig and ITIM domains Human genes 0.000 description 1
• 102100035268 T-cell surface protein tactile Human genes 0.000 description 1
• 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 1
• BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 1
• 102100040653 Tryptophan 2,3-dioxygenase Human genes 0.000 description 1
• 101710136122 Tryptophan 2,3-dioxygenase Proteins 0.000 description 1
• 102100028785 Tumor necrosis factor receptor superfamily member 14 Human genes 0.000 description 1
• 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 1
• 102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 description 1
• 108010079206 V-Set Domain-Containing T-Cell Activation Inhibitor 1 Proteins 0.000 description 1
• 102100038929 V-set domain-containing T-cell activation inhibitor 1 Human genes 0.000 description 1
• 102100038282 V-type immunoglobulin domain-containing suppressor of T-cell activation Human genes 0.000 description 1
• 102000009524 Vascular Endothelial Growth Factor A Human genes 0.000 description 1
• 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
• 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
• JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
• 208000027418 Wounds and injury Diseases 0.000 description 1
• PSLUFJFHTBIXMW-WYEYVKMPSA-N [(3r,4ar,5s,6s,6as,10s,10ar,10bs)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-pyridin-2-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2h-benzo[f]chromen-5-yl] acetate Chemical compound O([C@@H]1[C@@H]([C@]2(O[C@](C)(CC(=O)[C@]2(O)[C@@]2(C)[C@@H](O)CCC(C)(C)[C@@H]21)C=C)C)OC(=O)C)C(=O)NCCC1=CC=CC=N1 PSLUFJFHTBIXMW-WYEYVKMPSA-N 0.000 description 1
• 238000009825 accumulation Methods 0.000 description 1
• RAFKCLFWELPONH-UHFFFAOYSA-N acetonitrile;dichloromethane Chemical compound CC#N.ClCCl RAFKCLFWELPONH-UHFFFAOYSA-N 0.000 description 1
• QQAGXJMLHRUMJF-UHFFFAOYSA-N acetylene trimethylsilane Chemical group C#C.C[SiH](C)C QQAGXJMLHRUMJF-UHFFFAOYSA-N 0.000 description 1
• 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
• 239000004480 active ingredient Substances 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 230000006838 adverse reaction Effects 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 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 1
• 208000030961 allergic reaction Diseases 0.000 description 1
• 230000003321 amplification Effects 0.000 description 1
• 230000006481 angiogenic pathway Effects 0.000 description 1
• 230000002424 anti-apoptotic effect Effects 0.000 description 1
• 230000002095 anti-migrative effect Effects 0.000 description 1
• 230000000259 anti-tumor effect Effects 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 150000008430 aromatic amides Chemical class 0.000 description 1
• 238000003491 array Methods 0.000 description 1
• 230000004900 autophagic degradation Effects 0.000 description 1
• 229960002756 azacitidine Drugs 0.000 description 1
• 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 1
• 229960002170 azathioprine Drugs 0.000 description 1
• LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
• 230000004888 barrier function Effects 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
• 125000002619 bicyclic group Chemical group 0.000 description 1
• 230000007321 biological mechanism Effects 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
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 229910000024 caesium carbonate Inorganic materials 0.000 description 1
• 229960004117 capecitabine Drugs 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• 229960004562 carboplatin Drugs 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 239000003054 catalyst Substances 0.000 description 1
• 238000004113 cell culture Methods 0.000 description 1
• 230000022131 cell cycle Effects 0.000 description 1
• 230000030833 cell death Effects 0.000 description 1
• 230000024245 cell differentiation Effects 0.000 description 1
• 230000003915 cell function Effects 0.000 description 1
• 230000005754 cellular signaling Effects 0.000 description 1
• PRQROPMIIGLWRP-BZSNNMDCSA-N chemotactic peptide Chemical compound CSCC[C@H](NC=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 PRQROPMIIGLWRP-BZSNNMDCSA-N 0.000 description 1
• 230000035605 chemotaxis Effects 0.000 description 1
• 238000002512 chemotherapy Methods 0.000 description 1
• 239000012829 chemotherapy agent Substances 0.000 description 1
• JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
• 229960004630 chlorambucil Drugs 0.000 description 1
• 230000001684 chronic effect Effects 0.000 description 1
• 210000004081 cilia Anatomy 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
• 229940040387 citrus pectin Drugs 0.000 description 1
• 239000009194 citrus pectin Substances 0.000 description 1
• 238000004040 coloring Methods 0.000 description 1
• 229940125758 compound 15 Drugs 0.000 description 1
• 229940125846 compound 25 Drugs 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 1
• GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
• 238000004132 cross linking Methods 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 150000001934 cyclohexanes Chemical class 0.000 description 1
• 229960004397 cyclophosphamide Drugs 0.000 description 1
• 229960000684 cytarabine Drugs 0.000 description 1
• 108010057085 cytokine receptors Proteins 0.000 description 1
• 102000003675 cytokine receptors Human genes 0.000 description 1
• 229960000975 daunorubicin Drugs 0.000 description 1
• STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• 230000002939 deleterious effect Effects 0.000 description 1
• 210000004443 dendritic cell Anatomy 0.000 description 1
• 238000010511 deprotection reaction Methods 0.000 description 1
• 230000001066 destructive effect Effects 0.000 description 1
• 238000003745 diagnosis Methods 0.000 description 1
• MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical class C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 1
• GRTGGSXWHGKRSB-UHFFFAOYSA-N dichloromethyl methyl ether Chemical compound COC(Cl)Cl GRTGGSXWHGKRSB-UHFFFAOYSA-N 0.000 description 1
• 239000000539 dimer Substances 0.000 description 1
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
• 229960003668 docetaxel Drugs 0.000 description 1
• ZWAOHEXOSAUJHY-ZIYNGMLESA-N doxifluridine Chemical compound O[C@@H]1[C@H](O)[C@@H](C)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ZWAOHEXOSAUJHY-ZIYNGMLESA-N 0.000 description 1
• 229950005454 doxifluridine Drugs 0.000 description 1
• 229960004679 doxorubicin Drugs 0.000 description 1
• 239000012636 effector Substances 0.000 description 1
• 239000003480 eluent Substances 0.000 description 1
• 230000012202 endocytosis Effects 0.000 description 1
• 239000003623 enhancer Substances 0.000 description 1
• 230000002708 enhancing effect Effects 0.000 description 1
• 230000007515 enzymatic degradation Effects 0.000 description 1
• 230000007071 enzymatic hydrolysis Effects 0.000 description 1
• 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
• 229960001904 epirubicin Drugs 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 229960005420 etoposide Drugs 0.000 description 1
• 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 1
• 238000011156 evaluation Methods 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 230000002349 favourable effect Effects 0.000 description 1
• 230000003176 fibrotic effect Effects 0.000 description 1
• 239000000706 filtrate Substances 0.000 description 1
• 229960000390 fludarabine Drugs 0.000 description 1
• 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 1
• GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
• 238000000198 fluorescence anisotropy Methods 0.000 description 1
• IJJVMEJXYNJXOJ-UHFFFAOYSA-N fluquinconazole Chemical compound C=1C=C(Cl)C=C(Cl)C=1N1C(=O)C2=CC(F)=CC=C2N=C1N1C=NC=N1 IJJVMEJXYNJXOJ-UHFFFAOYSA-N 0.000 description 1
• 239000012634 fragment Substances 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 150000008195 galaktosides Chemical class 0.000 description 1
• 108010065785 galectin 5 Proteins 0.000 description 1
• SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
• 229960005277 gemcitabine Drugs 0.000 description 1
• 238000001415 gene therapy Methods 0.000 description 1
• 150000004676 glycans Chemical class 0.000 description 1
• 230000013595 glycosylation Effects 0.000 description 1
• 238000006206 glycosylation reaction Methods 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 230000001744 histochemical effect Effects 0.000 description 1
• 230000003301 hydrolyzing effect Effects 0.000 description 1
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
• 229960000908 idarubicin Drugs 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 230000028993 immune response Effects 0.000 description 1
• 230000036039 immunity Effects 0.000 description 1
• 230000002055 immunohistochemical effect Effects 0.000 description 1
• 230000001506 immunosuppresive effect Effects 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 230000002757 inflammatory effect Effects 0.000 description 1
• 230000028709 inflammatory response Effects 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 208000014674 injury Diseases 0.000 description 1
• 102000006495 integrins Human genes 0.000 description 1
• 108010044426 integrins Proteins 0.000 description 1
• 229940117681 interleukin-12 Drugs 0.000 description 1
• 108010074108 interleukin-21 Proteins 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 230000010189 intracellular transport Effects 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• DPDXVBIWZBJGSX-XUTVFYLZSA-N isoboonein Chemical compound C1C(=O)OC[C@@H]2[C@@H](C)[C@@H](O)C[C@@H]21 DPDXVBIWZBJGSX-XUTVFYLZSA-N 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
• 150000002545 isoxazoles Chemical class 0.000 description 1
• 239000010410 layer Substances 0.000 description 1
• 229960004942 lenalidomide Drugs 0.000 description 1
• 150000007517 lewis acids Chemical class 0.000 description 1
• 238000002514 liquid chromatography mass spectrum Methods 0.000 description 1
• 201000005202 lung cancer Diseases 0.000 description 1
• 208000020816 lung neoplasm Diseases 0.000 description 1
• 230000002132 lysosomal effect Effects 0.000 description 1
• 230000008824 lysosomal permeabilization Effects 0.000 description 1
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
• 235000019341 magnesium sulphate Nutrition 0.000 description 1
• 238000012423 maintenance Methods 0.000 description 1
• 239000003550 marker Substances 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
• 229960004961 mechlorethamine Drugs 0.000 description 1
• SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
• 229960001924 melphalan Drugs 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 1
• 229960001428 mercaptopurine Drugs 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 208000037819 metastatic cancer Diseases 0.000 description 1
• 208000011575 metastatic malignant neoplasm Diseases 0.000 description 1
• 229960000485 methotrexate Drugs 0.000 description 1
• 210000003879 microtubule-organizing center Anatomy 0.000 description 1
• 230000003278 mimic effect Effects 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 229960001156 mitoxantrone Drugs 0.000 description 1
• 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 1
• 230000009456 molecular mechanism Effects 0.000 description 1
• 210000001616 monocyte Anatomy 0.000 description 1
• 150000002772 monosaccharides Chemical class 0.000 description 1
• 238000007040 multi-step synthesis reaction Methods 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• 239000002105 nanoparticle Substances 0.000 description 1
• 229930014626 natural product Natural products 0.000 description 1
• 230000006654 negative regulation of apoptotic process Effects 0.000 description 1
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 230000009826 neoplastic cell growth Effects 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• XZXHXSATPCNXJR-ZIADKAODSA-N nintedanib Chemical compound O=C1NC2=CC(C(=O)OC)=CC=C2\C1=C(C=1C=CC=CC=1)\NC(C=C1)=CC=C1N(C)C(=O)CN1CCN(C)CC1 XZXHXSATPCNXJR-ZIADKAODSA-N 0.000 description 1
• 229960004378 nintedanib Drugs 0.000 description 1
• 230000025308 nuclear transport Effects 0.000 description 1
• 238000003199 nucleic acid amplification method Methods 0.000 description 1
• 238000011580 nude mouse model Methods 0.000 description 1
• 229920001542 oligosaccharide Polymers 0.000 description 1
• 150000002482 oligosaccharides Chemical class 0.000 description 1
• CGBJSGAELGCMKE-UHFFFAOYSA-N omipalisib Chemical compound COC1=NC=C(C=2C=C3C(C=4C=NN=CC=4)=CC=NC3=CC=2)C=C1NS(=O)(=O)C1=CC=C(F)C=C1F CGBJSGAELGCMKE-UHFFFAOYSA-N 0.000 description 1
• 230000008520 organization Effects 0.000 description 1
• 230000002018 overexpression Effects 0.000 description 1
• 125000001715 oxadiazolyl group Chemical group 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 239000007800 oxidant agent Substances 0.000 description 1
• 230000001590 oxidative effect Effects 0.000 description 1
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
• 229960001592 paclitaxel Drugs 0.000 description 1
• 229910052763 palladium Inorganic materials 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 229920001277 pectin Polymers 0.000 description 1
• 239000001814 pectin Substances 0.000 description 1
• 235000010987 pectin Nutrition 0.000 description 1
• 229960005079 pemetrexed Drugs 0.000 description 1
• QOFFJEBXNKRSPX-ZDUSSCGKSA-N pemetrexed Chemical compound C1=N[C]2NC(N)=NC(=O)C2=C1CCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 QOFFJEBXNKRSPX-ZDUSSCGKSA-N 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 239000003208 petroleum Substances 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
• UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• 125000004928 piperidonyl group Chemical group 0.000 description 1
• 229960003073 pirfenidone Drugs 0.000 description 1
• ISWRGOKTTBVCFA-UHFFFAOYSA-N pirfenidone Chemical compound C1=C(C)C=CC(=O)N1C1=CC=CC=C1 ISWRGOKTTBVCFA-UHFFFAOYSA-N 0.000 description 1
• 108010048507 poliovirus receptor Proteins 0.000 description 1
• 229920000962 poly(amidoamine) Polymers 0.000 description 1
• 229920001282 polysaccharide Polymers 0.000 description 1
• 239000005017 polysaccharide Substances 0.000 description 1
• CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
• 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
• 235000015320 potassium carbonate Nutrition 0.000 description 1
• 229910000027 potassium carbonate Inorganic materials 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
• 230000000861 pro-apoptotic effect Effects 0.000 description 1
• 108090000765 processed proteins & peptides Proteins 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 238000004393 prognosis Methods 0.000 description 1
• 230000000770 proinflammatory effect Effects 0.000 description 1
• 230000035755 proliferation Effects 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 150000003180 prostaglandins Chemical class 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• 238000000159 protein binding assay Methods 0.000 description 1
• 230000002797 proteolythic effect Effects 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 230000005855 radiation Effects 0.000 description 1
• 230000012121 regulation of immune response Effects 0.000 description 1
• 210000003289 regulatory T cell Anatomy 0.000 description 1
• 230000008844 regulatory mechanism Effects 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 239000013557 residual solvent Substances 0.000 description 1
• 230000019254 respiratory burst Effects 0.000 description 1
• 210000002345 respiratory system Anatomy 0.000 description 1
• 230000004043 responsiveness Effects 0.000 description 1
• 229930002330 retinoic acid Natural products 0.000 description 1
• 229940120975 revlimid Drugs 0.000 description 1
• 210000003705 ribosome Anatomy 0.000 description 1
• 229940121324 romilkimab Drugs 0.000 description 1
• YKJOCSACAYXGDY-UHFFFAOYSA-N s-(3-chloro-5-methoxyphenyl) n,n-dimethylcarbamothioate Chemical compound COC1=CC(Cl)=CC(SC(=O)N(C)C)=C1 YKJOCSACAYXGDY-UHFFFAOYSA-N 0.000 description 1
• 229920006395 saturated elastomer Polymers 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
• 238000011896 sensitive detection Methods 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• PEGQOIGYZLJMIB-UHFFFAOYSA-N setogepram Chemical compound CCCCCC1=CC=CC(CC(O)=O)=C1 PEGQOIGYZLJMIB-UHFFFAOYSA-N 0.000 description 1
• 230000019491 signal transduction Effects 0.000 description 1
• 229950009513 simtuzumab Drugs 0.000 description 1
• 235000017557 sodium bicarbonate Nutrition 0.000 description 1
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
• WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
• 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
• 239000007790 solid phase Substances 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 230000002269 spontaneous effect Effects 0.000 description 1
• 150000003431 steroids Chemical class 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 125000000547 substituted alkyl group Chemical group 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 230000001629 suppression Effects 0.000 description 1
• 239000012622 synthetic inhibitor Substances 0.000 description 1
• 230000009897 systematic effect Effects 0.000 description 1
• 239000003826 tablet Substances 0.000 description 1
• RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
• 229960004964 temozolomide Drugs 0.000 description 1
• 229960001278 teniposide Drugs 0.000 description 1
• NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
• ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 238000004809 thin layer chromatography Methods 0.000 description 1
• 150000003556 thioamides Chemical class 0.000 description 1
• 229930192474 thiophene Natural products 0.000 description 1
• 230000036964 tight binding Effects 0.000 description 1
• 229960003087 tioguanine Drugs 0.000 description 1
• MNRILEROXIRVNJ-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=NC=N[C]21 MNRILEROXIRVNJ-UHFFFAOYSA-N 0.000 description 1
• 208000037816 tissue injury Diseases 0.000 description 1
• 230000007838 tissue remodeling Effects 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 125000004665 trialkylsilyl group Chemical group 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
• PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 1
• 229940094989 trimethylsilane Drugs 0.000 description 1
• 125000004417 unsaturated alkyl group Chemical group 0.000 description 1
• 229960000653 valrubicin Drugs 0.000 description 1
• ZOCKGBMQLCSHFP-KQRAQHLDSA-N valrubicin Chemical compound O([C@H]1C[C@](CC2=C(O)C=3C(=O)C4=CC=CC(OC)=C4C(=O)C=3C(O)=C21)(O)C(=O)COC(=O)CCCC)[C@H]1C[C@H](NC(=O)C(F)(F)F)[C@H](O)[C@H](C)O1 ZOCKGBMQLCSHFP-KQRAQHLDSA-N 0.000 description 1
• 229960003048 vinblastine Drugs 0.000 description 1
• JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
• 229960004528 vincristine Drugs 0.000 description 1
• OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
• OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
• 229960004355 vindesine Drugs 0.000 description 1
• UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
• 229960002066 vinorelbine Drugs 0.000 description 1
• GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1