TW201739744A - 治療用化合物 - Google Patents

Info

Publication number

TW201739744A

TW201739744A TW106112891A TW106112891A TW201739744A TW 201739744 A TW201739744 A TW 201739744A TW 106112891 A TW106112891 A TW 106112891A TW 106112891 A TW106112891 A TW 106112891A TW 201739744 A TW201739744 A TW 201739744A

Authority

TW

Taiwan

Prior art keywords

group

alkyl

pharmaceutically acceptable

acceptable salt

cycloalkyl

Prior art date

2016-04-18

Links

• Espacenet
• Global Dossier
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 197
• 230000001225 therapeutic effect Effects 0.000 title abstract description 10
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 139
• 238000000034 method Methods 0.000 claims abstract description 58
• 125000000217 alkyl group Chemical group 0.000 claims description 189
• -1 heterocyclic alkane Chemical class 0.000 claims description 164
• 229910052736 halogen Inorganic materials 0.000 claims description 134
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 116
• 125000001072 heteroaryl group Chemical group 0.000 claims description 108
• 125000003118 aryl group Chemical group 0.000 claims description 100
• 229910052739 hydrogen Inorganic materials 0.000 claims description 100
• 150000003839 salts Chemical class 0.000 claims description 100
• 239000001257 hydrogen Substances 0.000 claims description 97
• 150000002367 halogens Chemical class 0.000 claims description 90
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 78
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 78
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 78
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 63
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 61
• 229910052757 nitrogen Inorganic materials 0.000 claims description 41
• 125000003545 alkoxy group Chemical group 0.000 claims description 32
• 229910052799 carbon Inorganic materials 0.000 claims description 20
• 125000004475 heteroaralkyl group Chemical group 0.000 claims description 19
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
• 210000004027 cell Anatomy 0.000 claims description 16
• QDHFHIQKOVNCNC-UHFFFAOYSA-N butane-1-sulfonic acid Chemical compound CCCCS(O)(=O)=O QDHFHIQKOVNCNC-UHFFFAOYSA-N 0.000 claims description 15
• HNDXKIMMSFCCFW-UHFFFAOYSA-N propane-2-sulphonic acid Chemical compound CC(C)S(O)(=O)=O HNDXKIMMSFCCFW-UHFFFAOYSA-N 0.000 claims description 12
• 150000001335 aliphatic alkanes Chemical class 0.000 claims description 11
• 150000001412 amines Chemical class 0.000 claims description 11
• 210000000068 Th17 cell Anatomy 0.000 claims description 10
• 125000006416 CBr Chemical group BrC* 0.000 claims description 9
• 125000006414 CCl Chemical group ClC* 0.000 claims description 9
• 230000002401 inhibitory effect Effects 0.000 claims description 9
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 8
• 125000005842 heteroatom Chemical group 0.000 claims description 8
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
• 239000008194 pharmaceutical composition Substances 0.000 claims description 8
• 230000002757 inflammatory effect Effects 0.000 claims description 7
• 201000006417 multiple sclerosis Diseases 0.000 claims description 7
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 7
• 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 6
• 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 5
• 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 5
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
• 230000001900 immune effect Effects 0.000 claims description 5
• 229910052760 oxygen Inorganic materials 0.000 claims description 5
• 239000001301 oxygen Substances 0.000 claims description 5
• 230000003915 cell function Effects 0.000 claims description 4
• 208000011231 Crohn disease Diseases 0.000 claims description 3
• 201000004681 Psoriasis Diseases 0.000 claims description 3
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
• XKPFLKWPESVZJF-UHFFFAOYSA-N 3,3,3-trifluoropropane-1-sulfonic acid Chemical compound OS(=O)(=O)CCC(F)(F)F XKPFLKWPESVZJF-UHFFFAOYSA-N 0.000 claims description 2
• CHJYKNDQMVDBKS-UHFFFAOYSA-N 4,4,4-trifluorobutane-1-sulfonic acid Chemical compound OS(=O)(=O)CCCC(F)(F)F CHJYKNDQMVDBKS-UHFFFAOYSA-N 0.000 claims description 2
• UMTNBTMDFMRZAN-UHFFFAOYSA-N acetic acid;sulfonylurea Chemical compound CC(O)=O.NC(=O)N=S(=O)=O UMTNBTMDFMRZAN-UHFFFAOYSA-N 0.000 claims description 2
• 150000002431 hydrogen Chemical class 0.000 claims 11
• XBIAGSJDARBSKG-UHFFFAOYSA-N 1-hydroxypyrrole Chemical compound ON1C=CC=C1 XBIAGSJDARBSKG-UHFFFAOYSA-N 0.000 claims 1
• RSOJSFYJLQADDM-UHFFFAOYSA-N ethanesulfonamide Chemical compound [CH2]CS(N)(=O)=O RSOJSFYJLQADDM-UHFFFAOYSA-N 0.000 claims 1
• 239000000203 mixture Substances 0.000 abstract description 91
• 102000001805 Bromodomains Human genes 0.000 abstract description 31
• 108050009021 Bromodomains Proteins 0.000 abstract description 31
• 108090000623 proteins and genes Proteins 0.000 abstract description 28
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 26
• 102000004169 proteins and genes Human genes 0.000 abstract description 25
• 206010028980 Neoplasm Diseases 0.000 abstract description 22
• 201000010099 disease Diseases 0.000 abstract description 19
• 201000011510 cancer Diseases 0.000 abstract description 15
• 230000005764 inhibitory process Effects 0.000 abstract description 15
• 230000001404 mediated effect Effects 0.000 abstract description 10
• 208000027866 inflammatory disease Diseases 0.000 abstract description 8
• 230000001594 aberrant effect Effects 0.000 abstract description 2
• 230000005754 cellular signaling Effects 0.000 abstract description 2
• 230000006718 epigenetic regulation Effects 0.000 abstract description 2
• 102000006947 Histones Human genes 0.000 abstract 1
• 108010033040 Histones Proteins 0.000 abstract 1
• DTERQYGMUDWYAZ-ZETCQYMHSA-N N(6)-acetyl-L-lysine Chemical group CC(=O)NCCCC[C@H]([NH3+])C([O-])=O DTERQYGMUDWYAZ-ZETCQYMHSA-N 0.000 abstract 1
• 230000001613 neoplastic effect Effects 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 122
• 125000004435 hydrogen atom Chemical class [H]* 0.000 description 78
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 76
• 235000019439 ethyl acetate Nutrition 0.000 description 64
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 64
• 125000005843 halogen group Chemical group 0.000 description 55
• OVIZSQRQYWEGON-UHFFFAOYSA-N butane-1-sulfonamide Chemical compound CCCCS(N)(=O)=O OVIZSQRQYWEGON-UHFFFAOYSA-N 0.000 description 53
• LKPNRYQIVWIRLV-UHFFFAOYSA-N 5-[2-(2,4-difluorophenoxy)-6-methylsulfonylpyrimidin-4-yl]-1,3-dimethylpyridin-2-one Chemical compound FC1=C(OC2=NC(=CC(=N2)C=2C=C(C(N(C=2)C)=O)C)S(=O)(=O)C)C=CC(=C1)F LKPNRYQIVWIRLV-UHFFFAOYSA-N 0.000 description 51
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 49
• 125000004432 carbon atom Chemical group C* 0.000 description 41
• 239000011734 sodium Substances 0.000 description 37
• 239000000243 solution Substances 0.000 description 34
• 125000000304 alkynyl group Chemical group 0.000 description 31
• 125000002947 alkylene group Chemical group 0.000 description 30
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 28
• 239000012267 brine Substances 0.000 description 28
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 28
• 239000012044 organic layer Substances 0.000 description 27
• 239000000126 substance Substances 0.000 description 23
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 21
• 238000006243 chemical reaction Methods 0.000 description 21
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 21
• 239000002585 base Substances 0.000 description 19
• 239000000460 chlorine Substances 0.000 description 19
• 238000005859 coupling reaction Methods 0.000 description 18
• 239000011541 reaction mixture Substances 0.000 description 18
• 125000003342 alkenyl group Chemical group 0.000 description 17
• 125000002837 carbocyclic group Chemical group 0.000 description 17
• HHVFVHIUOMMWRN-UHFFFAOYSA-N 5-bromo-1-methylpyridin-2-one Chemical class CN1C=C(Br)C=CC1=O HHVFVHIUOMMWRN-UHFFFAOYSA-N 0.000 description 16
• 230000008878 coupling Effects 0.000 description 16
• 238000010168 coupling process Methods 0.000 description 16
• 125000001424 substituent group Chemical group 0.000 description 16
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
• 238000004132 cross linking Methods 0.000 description 15
• 230000008569 process Effects 0.000 description 15
• 125000004452 carbocyclyl group Chemical group 0.000 description 14
• 238000001816 cooling Methods 0.000 description 14
• 125000003709 fluoroalkyl group Chemical group 0.000 description 14
• 229910052763 palladium Inorganic materials 0.000 description 14
• SJMCLWCCNYAWRQ-UHFFFAOYSA-N propane-2-sulfonamide Chemical compound CC(C)S(N)(=O)=O SJMCLWCCNYAWRQ-UHFFFAOYSA-N 0.000 description 14
• 230000002829 reductive effect Effects 0.000 description 13
• 238000006467 substitution reaction Methods 0.000 description 13
• NXXYKOUNUYWIHA-UHFFFAOYSA-N 2,6-Dimethylphenol Chemical compound CC1=CC=CC(C)=C1O NXXYKOUNUYWIHA-UHFFFAOYSA-N 0.000 description 12
• 239000002253 acid Substances 0.000 description 12
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 12
• 239000000651 prodrug Substances 0.000 description 12
• 229940002612 prodrug Drugs 0.000 description 12
• 238000003786 synthesis reaction Methods 0.000 description 12
• 210000001519 tissue Anatomy 0.000 description 12
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 11
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 11
• 239000003153 chemical reaction reagent Substances 0.000 description 11
• 238000002360 preparation method Methods 0.000 description 11
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 10
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 10
• 239000003112 inhibitor Substances 0.000 description 10
• 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 10
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 10
• 102100029895 Bromodomain-containing protein 4 Human genes 0.000 description 9
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• 238000003818 flash chromatography Methods 0.000 description 9
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 9
• 239000007787 solid Substances 0.000 description 9
• 238000003756 stirring Methods 0.000 description 9
• 229940124530 sulfonamide Drugs 0.000 description 9
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 8
• RANCECPPZPIPNO-UHFFFAOYSA-N 2,5-dichlorophenol Chemical compound OC1=CC(Cl)=CC=C1Cl RANCECPPZPIPNO-UHFFFAOYSA-N 0.000 description 8
• 230000015572 biosynthetic process Effects 0.000 description 8
• 125000004122 cyclic group Chemical group 0.000 description 8
• 125000004433 nitrogen atom Chemical group N* 0.000 description 8
• 210000003289 regulatory T cell Anatomy 0.000 description 8
• 229910000104 sodium hydride Inorganic materials 0.000 description 8
• 125000005323 thioketone group Chemical group 0.000 description 8
• UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical class ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 description 7
• QRXMUCSWCMTJGU-UHFFFAOYSA-N 5-bromo-4-chloro-3-indolyl phosphate Chemical compound C1=C(Br)C(Cl)=C2C(OP(O)(=O)O)=CNC2=C1 QRXMUCSWCMTJGU-UHFFFAOYSA-N 0.000 description 7
• 230000008901 benefit Effects 0.000 description 7
• 208000035475 disorder Diseases 0.000 description 7
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
• 125000003107 substituted aryl group Chemical group 0.000 description 7
• VEKIYFGCEAJDDT-UHFFFAOYSA-N 2-pyridin-3-ylpyridine Chemical group N1=CC=CC=C1C1=CC=CN=C1 VEKIYFGCEAJDDT-UHFFFAOYSA-N 0.000 description 6
• XJPZKYIHCLDXST-UHFFFAOYSA-N 4,6-dichloropyrimidine Chemical compound ClC1=CC(Cl)=NC=N1 XJPZKYIHCLDXST-UHFFFAOYSA-N 0.000 description 6
• 208000023275 Autoimmune disease Diseases 0.000 description 6
• 108091005625 BRD4 Proteins 0.000 description 6
• 102100021975 CREB-binding protein Human genes 0.000 description 6
• 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 6
• 101000896987 Homo sapiens CREB-binding protein Proteins 0.000 description 6
• 125000004429 atom Chemical group 0.000 description 6
• 150000001721 carbon Chemical group 0.000 description 6
• 230000006870 function Effects 0.000 description 6
• 125000000524 functional group Chemical group 0.000 description 6
• VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical compound C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 description 6
• 239000000047 product Substances 0.000 description 6
• DROIHSMGGKKIJT-UHFFFAOYSA-N propane-1-sulfonamide Chemical compound CCCS(N)(=O)=O DROIHSMGGKKIJT-UHFFFAOYSA-N 0.000 description 6
• 125000004076 pyridyl group Chemical group 0.000 description 6
• 229920006395 saturated elastomer Polymers 0.000 description 6
• 239000012047 saturated solution Substances 0.000 description 6
• 239000007858 starting material Substances 0.000 description 6
• 208000009415 Spinocerebellar Ataxias Diseases 0.000 description 5
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
• 150000001413 amino acids Chemical class 0.000 description 5
• 125000003277 amino group Chemical group 0.000 description 5
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
• 125000004431 deuterium atom Chemical group 0.000 description 5
• 239000012065 filter cake Substances 0.000 description 5
• 230000014509 gene expression Effects 0.000 description 5
• 150000004820 halides Chemical class 0.000 description 5
• 150000002430 hydrocarbons Chemical group 0.000 description 5
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
• 125000002971 oxazolyl group Chemical group 0.000 description 5
• 125000004430 oxygen atom Chemical group O* 0.000 description 5
• 239000000725 suspension Substances 0.000 description 5
• WYLZKEAKTKRGKT-UHFFFAOYSA-N 1,3-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-one Chemical compound CN1C(=O)C(C)=CC(B2OC(C)(C)C(C)(C)O2)=C1 WYLZKEAKTKRGKT-UHFFFAOYSA-N 0.000 description 4
• CFBCZETZIPZOGW-UHFFFAOYSA-N 1-benzofuran-4-ol Chemical compound OC1=CC=CC2=C1C=CO2 CFBCZETZIPZOGW-UHFFFAOYSA-N 0.000 description 4
• NVWVWEWVLBKPSM-UHFFFAOYSA-N 2,4-difluorophenol Chemical compound OC1=CC=C(F)C=C1F NVWVWEWVLBKPSM-UHFFFAOYSA-N 0.000 description 4
• XWALISSRSGMCSU-UHFFFAOYSA-N 6-bromo-2-methylisoquinolin-1-one Chemical compound BrC1=CC=C2C(=O)N(C)C=CC2=C1 XWALISSRSGMCSU-UHFFFAOYSA-N 0.000 description 4
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 4
• BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 4
• KNMIQFRDNIQEAT-UHFFFAOYSA-N C(CCCCCCCCC)N.CC(C)S(=O)(=O)O Chemical compound C(CCCCCCCCC)N.CC(C)S(=O)(=O)O KNMIQFRDNIQEAT-UHFFFAOYSA-N 0.000 description 4
• 102000005636 Cyclic AMP Response Element-Binding Protein Human genes 0.000 description 4
• 108010045171 Cyclic AMP Response Element-Binding Protein Proteins 0.000 description 4
• 102000013691 Interleukin-17 Human genes 0.000 description 4
• 108050003558 Interleukin-17 Proteins 0.000 description 4
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
• 230000021736 acetylation Effects 0.000 description 4
• 125000004450 alkenylene group Chemical group 0.000 description 4
• 239000003937 drug carrier Substances 0.000 description 4
• 238000001727 in vivo Methods 0.000 description 4
• 239000000543 intermediate Substances 0.000 description 4
• 239000010410 layer Substances 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• 125000002950 monocyclic group Chemical group 0.000 description 4
• BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 4
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 4
• 239000003921 oil Substances 0.000 description 4
• 230000037361 pathway Effects 0.000 description 4
• 108090000765 processed proteins & peptides Proteins 0.000 description 4
• 238000000746 purification Methods 0.000 description 4
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 4
• 239000002904 solvent Substances 0.000 description 4
• 150000003456 sulfonamides Chemical class 0.000 description 4
• 238000010189 synthetic method Methods 0.000 description 4
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
• 108091006108 transcriptional coactivators Proteins 0.000 description 4
• 238000012546 transfer Methods 0.000 description 4
• CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 4
• DROUVIKCNOHKBA-UHFFFAOYSA-N 4,6-dichloro-2-methylsulfonylpyrimidine Chemical compound CS(=O)(=O)C1=NC(Cl)=CC(Cl)=N1 DROUVIKCNOHKBA-UHFFFAOYSA-N 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• 206010003694 Atrophy Diseases 0.000 description 3
• 206010006187 Breast cancer Diseases 0.000 description 3
• 208000026310 Breast neoplasm Diseases 0.000 description 3
• 102100031048 Coiled-coil domain-containing protein 6 Human genes 0.000 description 3
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
• 208000023105 Huntington disease Diseases 0.000 description 3
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 3
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• 101710203930 RNA polymerase-associated transcription-specificity factor RAP94 Proteins 0.000 description 3
• KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 3
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
• 238000006640 acetylation reaction Methods 0.000 description 3
• 230000002378 acidificating effect Effects 0.000 description 3
• 150000007513 acids Chemical class 0.000 description 3
• 150000004703 alkoxides Chemical class 0.000 description 3
• 230000029936 alkylation Effects 0.000 description 3
• 238000005804 alkylation reaction Methods 0.000 description 3
• 238000004458 analytical method Methods 0.000 description 3
• 230000037444 atrophy Effects 0.000 description 3
• 239000011324 bead Substances 0.000 description 3
• 125000005605 benzo group Chemical group 0.000 description 3
• 239000012472 biological sample Substances 0.000 description 3
• 125000001246 bromo group Chemical group Br* 0.000 description 3
• 230000005587 bubbling Effects 0.000 description 3
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
• 230000024245 cell differentiation Effects 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
• 239000013078 crystal Substances 0.000 description 3
• 230000004069 differentiation Effects 0.000 description 3
• 239000012636 effector Substances 0.000 description 3
• 230000000694 effects Effects 0.000 description 3
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 3
• ZCRZCMUDOWDGOB-UHFFFAOYSA-N ethanesulfonimidic acid Chemical compound CCS(N)(=O)=O ZCRZCMUDOWDGOB-UHFFFAOYSA-N 0.000 description 3
• 239000000706 filtrate Substances 0.000 description 3
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 3
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 3
• 238000000338 in vitro Methods 0.000 description 3
• 230000003993 interaction Effects 0.000 description 3
• 201000005202 lung cancer Diseases 0.000 description 3
• 208000020816 lung neoplasm Diseases 0.000 description 3
• LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 3
• 239000002480 mineral oil Substances 0.000 description 3
• 235000010446 mineral oil Nutrition 0.000 description 3
• 238000010534 nucleophilic substitution reaction Methods 0.000 description 3
• 239000012074 organic phase Substances 0.000 description 3
• 125000003367 polycyclic group Chemical group 0.000 description 3
• 230000000069 prophylactic effect Effects 0.000 description 3
• 125000003226 pyrazolyl group Chemical group 0.000 description 3
• 125000000714 pyrimidinyl group Chemical group 0.000 description 3
• 150000003254 radicals Chemical class 0.000 description 3
• 239000000376 reactant Substances 0.000 description 3
• 230000004044 response Effects 0.000 description 3
• 229910052703 rhodium Inorganic materials 0.000 description 3
• 239000010948 rhodium Substances 0.000 description 3
• MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 3
• 229910052707 ruthenium Inorganic materials 0.000 description 3
• 230000028327 secretion Effects 0.000 description 3
• 238000001228 spectrum Methods 0.000 description 3
• 208000024891 symptom Diseases 0.000 description 3
• 239000003826 tablet Substances 0.000 description 3
• 238000002560 therapeutic procedure Methods 0.000 description 3
• 125000003396 thiol group Chemical group [H]S* 0.000 description 3
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
• 230000002103 transcriptional effect Effects 0.000 description 3
• 229910052725 zinc Inorganic materials 0.000 description 3
• 239000011701 zinc Substances 0.000 description 3
• SZNHPTZKPKUUNT-UHFFFAOYSA-N (1-ethyl-3,5-dimethylpyrazol-4-yl) benzoate Chemical compound C(C)N1N=C(C(=C1C)OC(C1=CC=CC=C1)=O)C SZNHPTZKPKUUNT-UHFFFAOYSA-N 0.000 description 2
• 125000006730 (C2-C5) alkynyl group Chemical group 0.000 description 2
• SRCOMEHNHCWSEN-UHFFFAOYSA-N 1-ethyl-3,5-dimethylpyrazol-4-ol Chemical compound CCN1N=C(C)C(O)=C1C SRCOMEHNHCWSEN-UHFFFAOYSA-N 0.000 description 2
• XXYLKHKDFDMHKP-UHFFFAOYSA-N 1-methyl-7-phenylmethoxyindole Chemical compound C=12N(C)C=CC2=CC=CC=1OCC1=CC=CC=C1 XXYLKHKDFDMHKP-UHFFFAOYSA-N 0.000 description 2
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 2
• IHWDSEPNZDYMNF-UHFFFAOYSA-N 1H-indol-2-amine Chemical compound C1=CC=C2NC(N)=CC2=C1 IHWDSEPNZDYMNF-UHFFFAOYSA-N 0.000 description 2
• WDAKSFIAMFFQAK-UHFFFAOYSA-N 2,4-dichloro-6-iodopyrimidine Chemical class ClC1=CC(I)=NC(Cl)=N1 WDAKSFIAMFFQAK-UHFFFAOYSA-N 0.000 description 2
• NGSKFMPSBUAUNE-UHFFFAOYSA-N 2,6-dichloro-4-iodopyridine Chemical compound ClC1=CC(I)=CC(Cl)=N1 NGSKFMPSBUAUNE-UHFFFAOYSA-N 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• MXALWBWOUGQNHF-UHFFFAOYSA-N 2-chloro-4-fluoro-6-methylphenol Chemical compound CC1=CC(F)=CC(Cl)=C1O MXALWBWOUGQNHF-UHFFFAOYSA-N 0.000 description 2
• YPNZJHFXFVLXSE-UHFFFAOYSA-N 2-chloro-6-methylphenol Chemical compound CC1=CC=CC(Cl)=C1O YPNZJHFXFVLXSE-UHFFFAOYSA-N 0.000 description 2
• WAGOKAFAVPFSKZ-UHFFFAOYSA-N 4,6-dichloro-2-[(2,4-difluorophenyl)methyl]pyrimidine Chemical compound FC1=CC(F)=CC=C1CC1=NC(Cl)=CC(Cl)=N1 WAGOKAFAVPFSKZ-UHFFFAOYSA-N 0.000 description 2
• YDDNEXJXFFLAGU-UHFFFAOYSA-N 4,6-dichloro-N-(2,4-difluorophenyl)pyrimidin-2-amine Chemical compound ClC1=NC(=NC(=C1)Cl)NC1=C(C=C(C=C1)F)F YDDNEXJXFFLAGU-UHFFFAOYSA-N 0.000 description 2
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
• GKQDDKKGDIVDAG-UHFFFAOYSA-N 4-fluoro-2-methylphenol Chemical compound CC1=CC(F)=CC=C1O GKQDDKKGDIVDAG-UHFFFAOYSA-N 0.000 description 2
• VRJHQPZVIGNGMX-UHFFFAOYSA-N 4-piperidinone Chemical compound O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 description 2
• OXWXNVDDIWVUCF-UHFFFAOYSA-N 5-(6-chloro-2-phenylpyrimidin-4-yl)-1,3-dimethylpyridin-2-one Chemical compound ClC1=CC(=NC(=N1)C1=CC=CC=C1)C=1C=C(C(N(C=1)C)=O)C OXWXNVDDIWVUCF-UHFFFAOYSA-N 0.000 description 2
• BEMNHCVHOICFLV-UHFFFAOYSA-N 5-[6-chloro-2-[(2,4-difluorophenyl)methyl]pyrimidin-4-yl]-1,3-dimethylpyridin-2-one Chemical compound ClC1=CC(=NC(=N1)CC1=C(C=C(C=C1)F)F)C=1C=C(C(N(C=1)C)=O)C BEMNHCVHOICFLV-UHFFFAOYSA-N 0.000 description 2
• NDMZZQRNZFWMEZ-UHFFFAOYSA-N 5-bromo-1h-pyridin-2-one Chemical class OC1=CC=C(Br)C=N1 NDMZZQRNZFWMEZ-UHFFFAOYSA-N 0.000 description 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
• 208000024827 Alzheimer disease Diseases 0.000 description 2
• 239000004475 Arginine Substances 0.000 description 2
• 239000005711 Benzoic acid Substances 0.000 description 2
• 206010005003 Bladder cancer Diseases 0.000 description 2
• 108010077544 Chromatin Proteins 0.000 description 2
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
• 208000035473 Communicable disease Diseases 0.000 description 2
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
• 108090000790 Enzymes Proteins 0.000 description 2
• 102000004190 Enzymes Human genes 0.000 description 2
• KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• 102100030703 Interleukin-22 Human genes 0.000 description 2
• 108010065637 Interleukin-23 Proteins 0.000 description 2
• 102000013264 Interleukin-23 Human genes 0.000 description 2
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
• 241001529936 Murinae Species 0.000 description 2
• GCWOPYDTTOVAEO-UHFFFAOYSA-N N-(2,6-dichloropyridin-4-yl)propane-2-sulfonamide Chemical compound ClC1=NC(=CC(=C1)NS(=O)(=O)C(C)C)Cl GCWOPYDTTOVAEO-UHFFFAOYSA-N 0.000 description 2
• 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 2
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
• IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 2
• 208000018737 Parkinson disease Diseases 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• 206010060862 Prostate cancer Diseases 0.000 description 2
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
• 210000001744 T-lymphocyte Anatomy 0.000 description 2
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 2
• 241000700605 Viruses Species 0.000 description 2
• 230000002159 abnormal effect Effects 0.000 description 2
• 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 2
• 239000012190 activator Substances 0.000 description 2
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
• MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
• 230000003110 anti-inflammatory effect Effects 0.000 description 2
• 230000006907 apoptotic process Effects 0.000 description 2
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
• 238000003556 assay Methods 0.000 description 2
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
• 235000010233 benzoic acid Nutrition 0.000 description 2
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
• 125000002619 bicyclic group Chemical group 0.000 description 2
• 210000004369 blood Anatomy 0.000 description 2
• 239000008280 blood Substances 0.000 description 2
• 208000029028 brain injury Diseases 0.000 description 2
• 230000031709 bromination Effects 0.000 description 2
• 238000005893 bromination reaction Methods 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
• 238000002619 cancer immunotherapy Methods 0.000 description 2
• 229910002091 carbon monoxide Inorganic materials 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 239000003054 catalyst Substances 0.000 description 2
• 230000004663 cell proliferation Effects 0.000 description 2
• 230000001413 cellular effect Effects 0.000 description 2
• 239000003795 chemical substances by application Substances 0.000 description 2
• 210000003483 chromatin Anatomy 0.000 description 2
• 238000004440 column chromatography Methods 0.000 description 2
• 238000004891 communication Methods 0.000 description 2
• 125000000392 cycloalkenyl group Chemical group 0.000 description 2
• 230000016396 cytokine production Effects 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 description 2
• 239000003814 drug Substances 0.000 description 2
• 230000008029 eradication Effects 0.000 description 2
• 150000002148 esters Chemical class 0.000 description 2
• 239000000284 extract Substances 0.000 description 2
• 210000003811 finger Anatomy 0.000 description 2
• 125000001153 fluoro group Chemical group F* 0.000 description 2
• 239000012458 free base Substances 0.000 description 2
• 102000027012 human bone sialoprotein (35-62) Human genes 0.000 description 2
• 108091003098 human bone sialoprotein (35-62) Proteins 0.000 description 2
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
• 230000007062 hydrolysis Effects 0.000 description 2
• 238000006460 hydrolysis reaction Methods 0.000 description 2
• 239000005457 ice water Substances 0.000 description 2
• 125000002632 imidazolidinyl group Chemical group 0.000 description 2
• 230000001771 impaired effect Effects 0.000 description 2
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 2
• 230000002458 infectious effect Effects 0.000 description 2
• 150000007529 inorganic bases Chemical class 0.000 description 2
• XMBWDFGMSWQBCA-YPZZEJLDSA-N iodane Chemical compound [125IH] XMBWDFGMSWQBCA-YPZZEJLDSA-N 0.000 description 2
• 230000000302 ischemic effect Effects 0.000 description 2
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• 208000032839 leukemia Diseases 0.000 description 2
• 239000003446 ligand Substances 0.000 description 2
• 230000000670 limiting effect Effects 0.000 description 2
• 150000002678 macrocyclic compounds Chemical class 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
• 239000000463 material Substances 0.000 description 2
• 230000007246 mechanism Effects 0.000 description 2
• 201000001441 melanoma Diseases 0.000 description 2
• QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• 229960005181 morphine Drugs 0.000 description 2
• 208000031225 myocardial ischemia Diseases 0.000 description 2
• 125000001624 naphthyl group Chemical group 0.000 description 2
• 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 2
• 238000005457 optimization Methods 0.000 description 2
• 150000007530 organic bases Chemical class 0.000 description 2
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
• 125000003386 piperidinyl group Chemical group 0.000 description 2
• 230000002062 proliferating effect Effects 0.000 description 2
• DMNHXVSTWJJMMA-UHFFFAOYSA-N propan-2-ylsulfanylmethyl acetate Chemical compound C(C)(C)SCOC(C)=O DMNHXVSTWJJMMA-UHFFFAOYSA-N 0.000 description 2
• KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 2
• 230000004952 protein activity Effects 0.000 description 2
• BBEAQIROQSPTKN-UHFFFAOYSA-N pyrene Chemical compound C1=CC=C2C=CC3=CC=CC4=CC=C1C2=C43 BBEAQIROQSPTKN-UHFFFAOYSA-N 0.000 description 2
• 125000000168 pyrrolyl group Chemical group 0.000 description 2
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
• 238000011160 research Methods 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 230000035939 shock Effects 0.000 description 2
• 150000003384 small molecules Chemical class 0.000 description 2
• 210000000278 spinal cord Anatomy 0.000 description 2
• 201000003624 spinocerebellar ataxia type 1 Diseases 0.000 description 2
• 125000004426 substituted alkynyl group Chemical group 0.000 description 2
• 239000000758 substrate Substances 0.000 description 2
• FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 2
• 229910052717 sulfur Inorganic materials 0.000 description 2
• 239000011593 sulfur Substances 0.000 description 2
• UQUYNGRHPOJDLJ-UHFFFAOYSA-N tert-butyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OC(C)(C)C UQUYNGRHPOJDLJ-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
• 125000001544 thienyl group Chemical group 0.000 description 2
• 238000004809 thin layer chromatography Methods 0.000 description 2
• 229930192474 thiophene Natural products 0.000 description 2
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
• 201000005112 urinary bladder cancer Diseases 0.000 description 2
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
• UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 2
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
• 125000006833 (C1-C5) alkylene group Chemical group 0.000 description 1
• 125000006650 (C2-C4) alkynyl group Chemical group 0.000 description 1
• WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
• JIHQDMXYYFUGFV-UHFFFAOYSA-N 1,3,5-triazine Chemical compound C1=NC=NC=N1 JIHQDMXYYFUGFV-UHFFFAOYSA-N 0.000 description 1
• FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 1
• 125000005871 1,3-benzodioxolyl group Chemical group 0.000 description 1
• KFQZBKCCLNSKOB-UHFFFAOYSA-N 1,3-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-pyridine Chemical compound CN1CC(=CC(=C1)B1OC(C(O1)(C)C)(C)C)C KFQZBKCCLNSKOB-UHFFFAOYSA-N 0.000 description 1
• RNXDVGDNKIARTM-UHFFFAOYSA-N 1,3-dimethyl-5-[2-methylsulfanyl-6-(propan-2-ylsulfonylmethyl)pyrimidin-4-yl]pyridin-2-one Chemical compound CN1C(C(=CC(=C1)C1=NC(=NC(=C1)CS(=O)(=O)C(C)C)SC)C)=O RNXDVGDNKIARTM-UHFFFAOYSA-N 0.000 description 1
• JBAFUGHVDBDJDO-UHFFFAOYSA-N 1,3-dimethyl-5-[2-methylsulfonyl-6-(propan-2-ylsulfonylmethyl)pyrimidin-4-yl]pyridin-2-one Chemical compound CS(=O)(=O)C1=NC(=CC(=N1)C=1C=C(C(N(C=1)C)=O)C)CS(=O)(=O)C(C)C JBAFUGHVDBDJDO-UHFFFAOYSA-N 0.000 description 1
• WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
• 125000005877 1,4-benzodioxanyl group Chemical group 0.000 description 1
• APWRZPQBPCAXFP-UHFFFAOYSA-N 1-(1-oxo-2H-isoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]pyrazole-4-carboxamide Chemical compound O=C1NC=CC2=C(C=CC=C12)N1N=CC(=C1C(F)(F)F)C(=O)NC1=CC(=NC=C1)C(F)(F)F APWRZPQBPCAXFP-UHFFFAOYSA-N 0.000 description 1
• IJUNZKOKAXJGRQ-UHFFFAOYSA-N 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-one Chemical compound C1=CC(=O)N(C)C=C1B1OC(C)(C)C(C)(C)O1 IJUNZKOKAXJGRQ-UHFFFAOYSA-N 0.000 description 1
• WXXOOVLYAHIFKW-UHFFFAOYSA-N 1-methylindol-7-ol Chemical compound C1=CC(O)=C2N(C)C=CC2=C1 WXXOOVLYAHIFKW-UHFFFAOYSA-N 0.000 description 1
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 1
• 150000007549 18-membered macrocycles Chemical class 0.000 description 1
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
• LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 1
• HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
• UIGMDMOGAQFIQT-UHFFFAOYSA-N 2,4-dichloro-6-(2,6-dimethylphenoxy)-1,3,5-triazine Chemical compound CC1=CC=CC(C)=C1OC1=NC(Cl)=NC(Cl)=N1 UIGMDMOGAQFIQT-UHFFFAOYSA-N 0.000 description 1
• WJQZZLQMLJPKQH-UHFFFAOYSA-N 2,4-dichloro-6-methylphenol Chemical group CC1=CC(Cl)=CC(Cl)=C1O WJQZZLQMLJPKQH-UHFFFAOYSA-N 0.000 description 1
• BTTNYQZNBZNDOR-UHFFFAOYSA-N 2,4-dichloropyrimidine Chemical class ClC1=CC=NC(Cl)=N1 BTTNYQZNBZNDOR-UHFFFAOYSA-N 0.000 description 1
• CEPCPXLLFXPZGW-UHFFFAOYSA-N 2,4-difluoroaniline Chemical compound NC1=CC=C(F)C=C1F CEPCPXLLFXPZGW-UHFFFAOYSA-N 0.000 description 1
• 125000006507 2,4-difluorobenzyl group Chemical group [H]C1=C(F)C([H])=C(F)C(=C1[H])C([H])([H])* 0.000 description 1
• AGAOESUOSOGZOD-UHFFFAOYSA-N 2-(2,4-difluorophenyl)acetonitrile Chemical compound FC1=CC=C(CC#N)C(F)=C1 AGAOESUOSOGZOD-UHFFFAOYSA-N 0.000 description 1
• UYGYKFRDEMVMBA-UHFFFAOYSA-N 2-[(2,4-difluorophenyl)methyl]-4-hydroxy-1h-pyrimidin-6-one Chemical compound OC1=CC(=O)NC(CC=2C(=CC(F)=CC=2)F)=N1 UYGYKFRDEMVMBA-UHFFFAOYSA-N 0.000 description 1
• IEQAICDLOKRSRL-UHFFFAOYSA-N 2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-dodecoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethanol Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCO IEQAICDLOKRSRL-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
• 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
• JRMAQQQTXDJDNC-UHFFFAOYSA-M 2-ethoxy-2-oxoacetate Chemical compound CCOC(=O)C([O-])=O JRMAQQQTXDJDNC-UHFFFAOYSA-M 0.000 description 1
• LTJBGZJJPIHUIB-UHFFFAOYSA-N 2-hydroxy-3-methylbenzonitrile Chemical group CC1=CC=CC(C#N)=C1O LTJBGZJJPIHUIB-UHFFFAOYSA-N 0.000 description 1
• AXDGIPMYJALRKV-UHFFFAOYSA-N 2-iodopyrimidine Chemical compound IC1=NC=CC=N1 AXDGIPMYJALRKV-UHFFFAOYSA-N 0.000 description 1
• DXMHWTUWSSJRID-UHFFFAOYSA-N 2-methyl-1-benzofuran-4-ol Chemical compound C1=CC=C2OC(C)=CC2=C1O DXMHWTUWSSJRID-UHFFFAOYSA-N 0.000 description 1
• MZSAMHOCTRNOIZ-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-phenylaniline Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(NC2=CC=CC=C2)C=CC=1 MZSAMHOCTRNOIZ-UHFFFAOYSA-N 0.000 description 1
• KRUDZWOELKQDJW-UHFFFAOYSA-N 3-amino-5-bromo-1-methylpyridin-2-one Chemical class CN1C=C(Br)C=C(N)C1=O KRUDZWOELKQDJW-UHFFFAOYSA-N 0.000 description 1
• VLRGXXKFHVJQOL-UHFFFAOYSA-N 3-chloropentane-2,4-dione Chemical compound CC(=O)C(Cl)C(C)=O VLRGXXKFHVJQOL-UHFFFAOYSA-N 0.000 description 1
• YTEIHWVCQJZNEN-UHFFFAOYSA-N 3-pyridin-4-ylpyridine Chemical compound C1=CN=CC(C=2C=CN=CC=2)=C1 YTEIHWVCQJZNEN-UHFFFAOYSA-N 0.000 description 1
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
• ACZGCWSMSTYWDQ-UHFFFAOYSA-N 3h-1-benzofuran-2-one Chemical compound C1=CC=C2OC(=O)CC2=C1 ACZGCWSMSTYWDQ-UHFFFAOYSA-N 0.000 description 1
• YVCWJYGMTPGLOE-UHFFFAOYSA-N 4,6-dichloro-2-(2,4-difluorophenoxy)pyrimidine Chemical compound ClC1=NC(=NC(=C1)Cl)OC1=C(C=C(C=C1)F)F YVCWJYGMTPGLOE-UHFFFAOYSA-N 0.000 description 1
• BZLDFFYTOLGJOK-UHFFFAOYSA-N 4,6-dichloro-2-(2,5-dichlorophenoxy)pyrimidine Chemical compound ClC1=NC(=NC(=C1)Cl)OC1=C(C=CC(=C1)Cl)Cl BZLDFFYTOLGJOK-UHFFFAOYSA-N 0.000 description 1
• GTFSDVZQNKCURY-UHFFFAOYSA-N 4,6-dichloro-2-(2-chloro-6-methylphenoxy)pyrimidine Chemical compound ClC1=NC(=NC(=C1)Cl)OC1=C(C=CC=C1C)Cl GTFSDVZQNKCURY-UHFFFAOYSA-N 0.000 description 1
• YMVNHXZFDQSCRK-UHFFFAOYSA-N 4,6-dichloro-2-iodopyrimidine Chemical compound ClC1=CC(Cl)=NC(I)=N1 YMVNHXZFDQSCRK-UHFFFAOYSA-N 0.000 description 1
• FCMLONIWOAGZJX-UHFFFAOYSA-N 4,6-dichloro-2-methylsulfanylpyrimidine Chemical compound CSC1=NC(Cl)=CC(Cl)=N1 FCMLONIWOAGZJX-UHFFFAOYSA-N 0.000 description 1
• JPZOAVGMSDSWSW-UHFFFAOYSA-N 4,6-dichloropyrimidin-2-amine Chemical compound NC1=NC(Cl)=CC(Cl)=N1 JPZOAVGMSDSWSW-UHFFFAOYSA-N 0.000 description 1
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
• QVIAMKXOQGCYCV-UHFFFAOYSA-N 4-methylpentan-1-amine Chemical compound CC(C)CCCN QVIAMKXOQGCYCV-UHFFFAOYSA-N 0.000 description 1
• SMSHIXOEBWOYJS-UHFFFAOYSA-N 5,6,7,8-tetrahydroquinazoline Chemical compound C1=NC=C2CCCCC2=N1 SMSHIXOEBWOYJS-UHFFFAOYSA-N 0.000 description 1
• KZFHXIZBIHUKLB-UHFFFAOYSA-N 5-(4,6-dichloropyrimidin-2-yl)-1,3-dimethylpyridin-2-one Chemical compound ClC1=NC(=NC(=C1)Cl)C=1C=C(C(N(C=1)C)=O)C KZFHXIZBIHUKLB-UHFFFAOYSA-N 0.000 description 1
• NGAIMIKTLZJOCS-UHFFFAOYSA-N 5-[2-(2,4-difluorophenoxy)-6-(ethylsulfonylmethyl)pyrimidin-4-yl]-1,3-dimethylpyridin-2-one Chemical compound FC1=C(OC2=NC(=CC(=N2)C=2C=C(C(N(C=2)C)=O)C)CS(=O)(=O)CC)C=CC(=C1)F NGAIMIKTLZJOCS-UHFFFAOYSA-N 0.000 description 1
• BQIOFFMPQOXOOJ-UHFFFAOYSA-N 5-[2-(2,4-difluorophenoxy)-6-(propan-2-ylsulfonylmethyl)pyrimidin-4-yl]-1,3-dimethylpyridin-2-one Chemical compound FC1=C(OC2=NC(=CC(=N2)C=2C=C(C(N(C=2)C)=O)C)CS(=O)(=O)C(C)C)C=CC(=C1)F BQIOFFMPQOXOOJ-UHFFFAOYSA-N 0.000 description 1
• DDYARIUCPPMZTB-UHFFFAOYSA-N 5-[2-(2,4-difluorophenoxy)-6-methylsulfanylpyrimidin-4-yl]-1,3-dimethylpyridin-2-one Chemical compound FC1=C(OC2=NC(=CC(=N2)C=2C=C(C(N(C=2)C)=O)C)SC)C=CC(=C1)F DDYARIUCPPMZTB-UHFFFAOYSA-N 0.000 description 1
• NCOKFAIEKXZJET-UHFFFAOYSA-N 5-[4-chloro-6-(2,6-dimethylphenoxy)-1,3,5-triazin-2-yl]-1,3-dimethylpyridin-2-one Chemical compound ClC1=NC(=NC(=N1)OC1=C(C=CC=C1C)C)C=1C=C(C(N(C=1)C)=O)C NCOKFAIEKXZJET-UHFFFAOYSA-N 0.000 description 1
• INMCYTFHSZNQGM-UHFFFAOYSA-N 5-[4-chloro-6-(2,6-dimethylphenoxy)pyrimidin-2-yl]-1,3-dimethylpyridin-2-one Chemical compound ClC1=NC(=NC(=C1)OC1=C(C=CC=C1C)C)C=1C=C(C(N(C=1)C)=O)C INMCYTFHSZNQGM-UHFFFAOYSA-N 0.000 description 1
• OWBVXKFSUFLCMK-UHFFFAOYSA-N 5-[6-chloro-2-(2,4-difluoroanilino)pyrimidin-4-yl]-1,3-dimethylpyridin-2-one Chemical compound ClC1=CC(=NC(=N1)NC1=C(C=C(C=C1)F)F)C=1C=C(C(N(C=1)C)=O)C OWBVXKFSUFLCMK-UHFFFAOYSA-N 0.000 description 1
• MXIKLHRJDWDEIA-UHFFFAOYSA-N 5-[6-chloro-2-(2,5-dichlorophenoxy)pyrimidin-4-yl]-1,3-dimethylpyridin-2-one Chemical compound ClC1=CC(=NC(=N1)OC1=C(C=CC(=C1)Cl)Cl)C=1C=C(C(N(C=1)C)=O)C MXIKLHRJDWDEIA-UHFFFAOYSA-N 0.000 description 1
• XHZKBTUKZWZCDU-UHFFFAOYSA-N 5-bromo-1-ethyl-3-methylpyridin-2-one Chemical compound CCN1C=C(Br)C=C(C)C1=O XHZKBTUKZWZCDU-UHFFFAOYSA-N 0.000 description 1
• HXPMRPRBABWPKL-UHFFFAOYSA-N 5-bromo-3-methyl-1h-pyridin-2-one Chemical compound CC1=CC(Br)=CN=C1O HXPMRPRBABWPKL-UHFFFAOYSA-N 0.000 description 1
• DIGZMTAFOACVBW-UHFFFAOYSA-N 7-phenylmethoxy-1h-indole Chemical compound C=1C=CC=2C=CNC=2C=1OCC1=CC=CC=C1 DIGZMTAFOACVBW-UHFFFAOYSA-N 0.000 description 1
• 150000007539 8-membered macrocycles Chemical class 0.000 description 1
• OQLZINXFSUDMHM-UHFFFAOYSA-N Acetamidine Chemical compound CC(N)=N OQLZINXFSUDMHM-UHFFFAOYSA-N 0.000 description 1
• 101710186015 Acetyltransferase Pat Proteins 0.000 description 1
• 208000016683 Adult T-cell leukemia/lymphoma Diseases 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
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 1
• KWIUHFFTVRNATP-UHFFFAOYSA-N Betaine Natural products C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 1
• 208000003174 Brain Neoplasms Diseases 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• 208000011691 Burkitt lymphomas Diseases 0.000 description 1
• JSKNSEXIGNBHMI-UHFFFAOYSA-N C(C)N1C(C(=CC(=C1)B1OC(C(O1)(C)C)(C)C)C)=O Chemical compound C(C)N1C(C(=CC(=C1)B1OC(C(O1)(C)C)(C)C)C)=O JSKNSEXIGNBHMI-UHFFFAOYSA-N 0.000 description 1
• NZYITINABNGOGF-UHFFFAOYSA-N C(C)S(=O)(=O)O.C(CCCCCCCCC)N Chemical compound C(C)S(=O)(=O)O.C(CCCCCCCCC)N NZYITINABNGOGF-UHFFFAOYSA-N 0.000 description 1
• 125000004649 C2-C8 alkynyl group Chemical group 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
• 239000004215 Carbon black (E152) Substances 0.000 description 1
• OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
• WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
• 208000004468 Craniofacial Abnormalities Diseases 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-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
• 108020004414 DNA Proteins 0.000 description 1
• 230000033616 DNA repair Effects 0.000 description 1
• 241000450599 DNA viruses Species 0.000 description 1
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
• XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
• 241000196324 Embryophyta Species 0.000 description 1
• 241000588724 Escherichia coli Species 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• 208000009386 Experimental Arthritis Diseases 0.000 description 1
• NRFQZTCQAYEXEE-UHFFFAOYSA-N Fenclorim Chemical compound ClC1=CC(Cl)=NC(C=2C=CC=CC=2)=N1 NRFQZTCQAYEXEE-UHFFFAOYSA-N 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 1
• 230000037057 G1 phase arrest Effects 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
• 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
• 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
• 239000007995 HEPES buffer Substances 0.000 description 1
• 208000007514 Herpes zoster Diseases 0.000 description 1
• 108091006054 His-tagged proteins Proteins 0.000 description 1
• 108090000246 Histone acetyltransferases Proteins 0.000 description 1
• 102000003893 Histone acetyltransferases Human genes 0.000 description 1
• 102000009331 Homeodomain Proteins Human genes 0.000 description 1
• 108010048671 Homeodomain Proteins Proteins 0.000 description 1
• 101000998151 Homo sapiens Interleukin-17F Proteins 0.000 description 1
• 101001131829 Homo sapiens P protein Proteins 0.000 description 1
• 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
• 241000701806 Human papillomavirus Species 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical group ON AVXURJPOCDRRFD-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
• 102100033454 Interleukin-17F Human genes 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
• 239000005909 Kieselgur Substances 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
• 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
• 238000005684 Liebig rearrangement reaction Methods 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
• 208000002569 Machado-Joseph Disease Diseases 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 208000036626 Mental retardation Diseases 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 206010028570 Myelopathy Diseases 0.000 description 1
• KWIUHFFTVRNATP-UHFFFAOYSA-O N,N,N-trimethylglycinium Chemical compound C[N+](C)(C)CC(O)=O KWIUHFFTVRNATP-UHFFFAOYSA-O 0.000 description 1
• XMCSZONJSVNTDE-UHFFFAOYSA-N N-[4-(1,5-dimethyl-6-oxopyridin-3-yl)-6-(2,6-dimethylphenoxy)pyridin-2-yl]propane-1-sulfonamide Chemical compound CC1=C(OC2=CC(=CC(=N2)NS(=O)(=O)CCC)C2=CN(C(C(=C2)C)=O)C)C(=CC=C1)C XMCSZONJSVNTDE-UHFFFAOYSA-N 0.000 description 1
• VOKHWXPPTMPIKL-UHFFFAOYSA-N N-[6-(1,5-dimethyl-6-oxopyridin-3-yl)-2-phenylpyrimidin-4-yl]propane-1-sulfonamide Chemical compound CN1C=C(C=C(C1=O)C)C1=CC(=NC(=N1)C1=CC=CC=C1)NS(=O)(=O)CCC VOKHWXPPTMPIKL-UHFFFAOYSA-N 0.000 description 1
• UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
• HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
• 150000001204 N-oxides Chemical class 0.000 description 1
• 239000007832 Na2SO4 Substances 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
• 102000010410 Nogo Proteins Human genes 0.000 description 1
• 108010077641 Nogo Proteins Proteins 0.000 description 1
• 102100027069 Odontogenic ameloblast-associated protein Human genes 0.000 description 1
• 101710091533 Odontogenic ameloblast-associated protein Proteins 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 235000008673 Persea americana Nutrition 0.000 description 1
• 240000002426 Persea americana var. drymifolia Species 0.000 description 1
• 108010020346 Polyglutamic Acid Proteins 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
• 108091027981 Response element Proteins 0.000 description 1
• 206010039281 Rubinstein-Taybi syndrome Diseases 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
• 201000003622 Spinocerebellar ataxia type 2 Diseases 0.000 description 1
• 208000036834 Spinocerebellar ataxia type 3 Diseases 0.000 description 1
• 201000003620 Spinocerebellar ataxia type 6 Diseases 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 108010090804 Streptavidin Proteins 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 229930006000 Sucrose Natural products 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
• LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical class OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
• UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
• 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
• PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 238000012338 Therapeutic targeting Methods 0.000 description 1
• 241000534944 Thia Species 0.000 description 1
• 108090000992 Transferases Proteins 0.000 description 1
• 102000004357 Transferases Human genes 0.000 description 1
• 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
• 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
• 208000036142 Viral infection Diseases 0.000 description 1
• 238000009825 accumulation Methods 0.000 description 1
• IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
• KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
• WDJHALXBUFZDSR-UHFFFAOYSA-M acetoacetate Chemical compound CC(=O)CC([O-])=O WDJHALXBUFZDSR-UHFFFAOYSA-M 0.000 description 1
• 108020002494 acetyltransferase Proteins 0.000 description 1
• 102000005421 acetyltransferase Human genes 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 239000004480 active ingredient Substances 0.000 description 1
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 201000006966 adult T-cell leukemia Diseases 0.000 description 1
• 150000001299 aldehydes Chemical class 0.000 description 1
• 125000001931 aliphatic group Chemical group 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 150000001342 alkaline earth metals Chemical class 0.000 description 1
• 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
• 230000002152 alkylating effect Effects 0.000 description 1
• AEMOLEFTQBMNLQ-BKBMJHBISA-N alpha-D-galacturonic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-BKBMJHBISA-N 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• 238000003016 alphascreen Methods 0.000 description 1
• 230000004075 alteration Effects 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 125000000539 amino acid group Chemical group 0.000 description 1
• 230000005809 anti-tumor immunity Effects 0.000 description 1
• 229960003121 arginine Drugs 0.000 description 1
• 159000000032 aromatic acids Chemical class 0.000 description 1
• 125000005018 aryl alkenyl group Chemical group 0.000 description 1
• 125000002102 aryl alkyloxo group Chemical group 0.000 description 1
• 230000001363 autoimmune Effects 0.000 description 1
• 150000007514 bases Chemical class 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000005873 benzo[d]thiazolyl group Chemical group 0.000 description 1
• 125000000928 benzodioxinyl group Chemical group O1C(=COC2=C1C=CC=C2)* 0.000 description 1
• 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
• 125000005874 benzothiadiazolyl group Chemical group 0.000 description 1
• 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-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
• 102000023732 binding proteins Human genes 0.000 description 1
• 108091008324 binding proteins Proteins 0.000 description 1
• 238000004166 bioassay Methods 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 1
• KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
• 239000004327 boric acid Substances 0.000 description 1
• 150000001638 boron Chemical class 0.000 description 1
• 229910052796 boron Inorganic materials 0.000 description 1
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
• 230000006931 brain damage Effects 0.000 description 1
• 231100000874 brain damage Toxicity 0.000 description 1
• SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 0.000 description 1
• RHDGNLCLDBVESU-UHFFFAOYSA-N but-3-en-4-olide Chemical compound O=C1CC=CO1 RHDGNLCLDBVESU-UHFFFAOYSA-N 0.000 description 1
• QDHFHIQKOVNCNC-UHFFFAOYSA-M butane-1-sulfonate Chemical compound CCCCS([O-])(=O)=O QDHFHIQKOVNCNC-UHFFFAOYSA-M 0.000 description 1
• SMKHNMZMZSWJDH-UHFFFAOYSA-N butane-1-sulfonate;decylazanium Chemical compound CCCCS([O-])(=O)=O.CCCCCCCCCC[NH3+] SMKHNMZMZSWJDH-UHFFFAOYSA-N 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
• 239000006227 byproduct Substances 0.000 description 1
• 210000004899 c-terminal region Anatomy 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
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 230000007960 cellular response to stress Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 239000013522 chelant Substances 0.000 description 1
• PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 1
• SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 238000005660 chlorination reaction Methods 0.000 description 1
• 150000001805 chlorine compounds Chemical class 0.000 description 1
• KVSASDOGYIBWTA-UHFFFAOYSA-N chloro benzoate Chemical compound ClOC(=O)C1=CC=CC=C1 KVSASDOGYIBWTA-UHFFFAOYSA-N 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
• 229960002023 chloroprocaine Drugs 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
• 108091006090 chromatin-associated proteins Proteins 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 210000000349 chromosome Anatomy 0.000 description 1
• 235000013985 cinnamic acid Nutrition 0.000 description 1
• 229930016911 cinnamic acid Natural products 0.000 description 1
• 229940001468 citrate Drugs 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• 239000012230 colorless oil Substances 0.000 description 1
• 230000000295 complement effect Effects 0.000 description 1
• 239000002131 composite material Substances 0.000 description 1
• 239000007891 compressed tablet Substances 0.000 description 1
• 238000009833 condensation Methods 0.000 description 1
• 230000005494 condensation Effects 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 description 1
• 150000001924 cycloalkanes Chemical class 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
• 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 1
• 125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 description 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• XCIXKGXIYUWCLL-HOSYLAQJSA-N cyclopentanol Chemical group O[13CH]1CCCC1 XCIXKGXIYUWCLL-HOSYLAQJSA-N 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 231100000433 cytotoxic Toxicity 0.000 description 1
• 230000001472 cytotoxic effect Effects 0.000 description 1
• 125000004652 decahydroisoquinolinyl group Chemical group C1(NCCC2CCCCC12)* 0.000 description 1
• 238000006114 decarboxylation reaction Methods 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 230000007547 defect Effects 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 230000002939 deleterious effect Effects 0.000 description 1
• 238000012217 deletion Methods 0.000 description 1
• 230000037430 deletion Effects 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 229910052805 deuterium Inorganic materials 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 230000018109 developmental process Effects 0.000 description 1
• 238000003745 diagnosis Methods 0.000 description 1
• 150000001991 dicarboxylic acids Chemical class 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
• ATUOYWHBWRKTHZ-UHFFFAOYSA-N dimethylmethane Natural products CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 1
• 235000011180 diphosphates Nutrition 0.000 description 1
• 238000007907 direct compression Methods 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 229940079593 drug Drugs 0.000 description 1
• 238000009510 drug design Methods 0.000 description 1
• 210000003162 effector t lymphocyte Anatomy 0.000 description 1
• 230000005611 electricity Effects 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 230000001973 epigenetic effect Effects 0.000 description 1
• 238000011067 equilibration Methods 0.000 description 1
• AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 1
• 229960002001 ethionamide Drugs 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 229940012017 ethylenediamine Drugs 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 230000017188 evasion or tolerance of host immune response Effects 0.000 description 1
• 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 1
• 239000012467 final product Substances 0.000 description 1
• GVEPBJHOBDJJJI-UHFFFAOYSA-N fluoranthrene Natural products C1=CC(C2=CC=CC=C22)=C3C2=CC=CC3=C1 GVEPBJHOBDJJJI-UHFFFAOYSA-N 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 235000011087 fumaric acid Nutrition 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 229920000370 gamma-poly(glutamate) polymer Polymers 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 238000001641 gel filtration chromatography Methods 0.000 description 1
• 238000005227 gel permeation chromatography Methods 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• 238000007429 general method Methods 0.000 description 1
• GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical group [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 description 1
• 210000001905 globus pallidus Anatomy 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
• 235000001727 glucose Nutrition 0.000 description 1
• 230000003394 haemopoietic effect Effects 0.000 description 1
• 210000001255 hallux Anatomy 0.000 description 1
• 125000000262 haloalkenyl group Chemical group 0.000 description 1
• 125000000232 haloalkynyl group Chemical group 0.000 description 1
• BCQZXOMGPXTTIC-UHFFFAOYSA-N halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 description 1
• 229960003132 halothane Drugs 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 239000001307 helium Substances 0.000 description 1
• 229910052734 helium Inorganic materials 0.000 description 1
• SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
• 210000002443 helper t lymphocyte Anatomy 0.000 description 1
• 210000000777 hematopoietic system Anatomy 0.000 description 1
• 125000005980 hexynyl group Chemical group 0.000 description 1
• 238000004128 high performance liquid chromatography 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
• 229960002885 histidine Drugs 0.000 description 1
• 230000005745 host immune response Effects 0.000 description 1
• 102000047119 human OCA2 Human genes 0.000 description 1
• 238000009396 hybridization Methods 0.000 description 1
• 229930195733 hydrocarbon Natural products 0.000 description 1
• 229940071870 hydroiodic acid Drugs 0.000 description 1
• 230000002209 hydrophobic effect Effects 0.000 description 1
• 125000005946 imidazo[1,2-a]pyridyl group Chemical group 0.000 description 1
• MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
• 125000002636 imidazolinyl group Chemical group 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 125000001841 imino group Chemical group [H]N=* 0.000 description 1
• 230000005746 immune checkpoint blockade Effects 0.000 description 1
• 230000028993 immune response Effects 0.000 description 1
• 210000000987 immune system Anatomy 0.000 description 1
• 238000009169 immunotherapy Methods 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 230000004968 inflammatory condition Effects 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 108010074108 interleukin-21 Proteins 0.000 description 1
• 108010074109 interleukin-22 Proteins 0.000 description 1
• 230000002601 intratumoral effect Effects 0.000 description 1
• 229940044173 iodine-125 Drugs 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• 239000003456 ion exchange resin Substances 0.000 description 1
• 229920003303 ion-exchange polymer Polymers 0.000 description 1
• 229910052742 iron Inorganic materials 0.000 description 1
• KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000005956 isoquinolyl group Chemical group 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 230000000155 isotopic effect Effects 0.000 description 1
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
• 125000003965 isoxazolidinyl group Chemical group 0.000 description 1
• 229940001447 lactate Drugs 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 210000000265 leukocyte Anatomy 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
• 210000002540 macrophage Anatomy 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
• 239000001095 magnesium carbonate Substances 0.000 description 1
• 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
• 229940049920 malate Drugs 0.000 description 1
• 239000011976 maleic acid Substances 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
• 230000003211 malignant effect Effects 0.000 description 1
• 150000002690 malonic acid derivatives Chemical class 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
• 229960002510 mandelic acid Drugs 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 238000004519 manufacturing process Methods 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 150000002739 metals Chemical class 0.000 description 1
• 125000005341 metaphosphate group Chemical group 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• KOHJSDUTMFLVTI-UHFFFAOYSA-N methyl 2-(6-chloro-2-methylsulfanylpyrimidin-4-yl)-2-propan-2-ylsulfonylacetate Chemical compound COC(C(S(=O)(=O)C(C)C)C1=NC(=NC(=C1)Cl)SC)=O KOHJSDUTMFLVTI-UHFFFAOYSA-N 0.000 description 1
• VKWSIYDRXGEJFJ-UHFFFAOYSA-N methyl 2-ethylsulfonylacetate Chemical compound CCS(=O)(=O)CC(=O)OC VKWSIYDRXGEJFJ-UHFFFAOYSA-N 0.000 description 1
• ZKWMTNKWNHSIHO-UHFFFAOYSA-N methyl 2-propan-2-ylsulfonylacetate Chemical compound COC(=O)CS(=O)(=O)C(C)C ZKWMTNKWNHSIHO-UHFFFAOYSA-N 0.000 description 1
• 229940095102 methyl benzoate Drugs 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 238000003032 molecular docking Methods 0.000 description 1
• 201000000585 muscular atrophy Diseases 0.000 description 1
• 230000035772 mutation Effects 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
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 210000004897 n-terminal region Anatomy 0.000 description 1
• 230000004770 neurodegeneration Effects 0.000 description 1
• 208000015122 neurodegenerative disease Diseases 0.000 description 1
• 210000000440 neutrophil Anatomy 0.000 description 1
• 239000002547 new drug Substances 0.000 description 1
• 229910052759 nickel Inorganic materials 0.000 description 1
• 150000002823 nitrates Chemical class 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 150000002825 nitriles Chemical class 0.000 description 1
• 125000006574 non-aromatic ring group Chemical group 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 125000005474 octanoate group Chemical group 0.000 description 1
• 125000002347 octyl 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])[H] 0.000 description 1
• 230000000771 oncological effect Effects 0.000 description 1
• 238000011275 oncology therapy Methods 0.000 description 1
• 239000006186 oral dosage form Substances 0.000 description 1
• 229940100629 oral lozenge Drugs 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 238000006053 organic reaction Methods 0.000 description 1
• 230000008520 organization Effects 0.000 description 1
• 229910052762 osmium Inorganic materials 0.000 description 1
• SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 description 1
• 125000001715 oxadiazolyl group Chemical group 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 125000000160 oxazolidinyl group Chemical group 0.000 description 1
• 230000003647 oxidation Effects 0.000 description 1
• 238000007254 oxidation reaction Methods 0.000 description 1
• 125000000466 oxiranyl group Chemical group 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 244000052769 pathogen Species 0.000 description 1
• 125000005981 pentynyl group Chemical group 0.000 description 1
• 239000002831 pharmacologic agent Substances 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 229950000688 phenothiazine Drugs 0.000 description 1
• 229940049953 phenylacetate Drugs 0.000 description 1
• WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
• 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 235000021317 phosphate Nutrition 0.000 description 1
• RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 230000000704 physical effect Effects 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 1
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
• 229920000768 polyamine Polymers 0.000 description 1
• 150000004032 porphyrins Chemical class 0.000 description 1
• 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
• 230000004481 post-translational protein modification Effects 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• 125000002924 primary amino group Chemical group [H]N([H])* 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
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• 239000001294 propane Substances 0.000 description 1
• 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
• 230000019639 protein methylation Effects 0.000 description 1
• 238000010926 purge Methods 0.000 description 1
• 239000012629 purifying agent Substances 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
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• 230000002285 radioactive effect Effects 0.000 description 1
• 230000035484 reaction time Effects 0.000 description 1
• 230000007115 recruitment Effects 0.000 description 1
• 210000000463 red nucleus Anatomy 0.000 description 1
• 238000006268 reductive amination reaction Methods 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 229940116351 sebacate Drugs 0.000 description 1
• CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• 229960004540 secukinumab Drugs 0.000 description 1
• 239000000741 silica gel Substances 0.000 description 1
• 229910002027 silica gel Inorganic materials 0.000 description 1
• 238000010898 silica gel chromatography Methods 0.000 description 1
• XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
• 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 1
• 229910052938 sodium sulfate Inorganic materials 0.000 description 1
• 235000011152 sodium sulphate Nutrition 0.000 description 1
• 239000012453 solvate Substances 0.000 description 1
• 238000003797 solvolysis reaction Methods 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 201000003594 spinocerebellar ataxia type 12 Diseases 0.000 description 1
• 201000003632 spinocerebellar ataxia type 7 Diseases 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 230000003068 static effect Effects 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 238000012916 structural analysis Methods 0.000 description 1
• TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
• 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 230000004083 survival effect Effects 0.000 description 1
• 208000011580 syndromic disease Diseases 0.000 description 1
• 230000002194 synthesizing effect Effects 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
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• 238000003419 tautomerization reaction Methods 0.000 description 1
• ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
• BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
• 150000003512 tertiary amines Chemical class 0.000 description 1
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
• VDZOOKBUILJEDG-UHFFFAOYSA-M tetrabutylammonium hydroxide Chemical compound [OH-].CCCC[N+](CCCC)(CCCC)CCCC VDZOOKBUILJEDG-UHFFFAOYSA-M 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
• RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 229960004559 theobromine Drugs 0.000 description 1
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 229940015849 thiophene Drugs 0.000 description 1
• 210000003813 thumb Anatomy 0.000 description 1
• 238000013518 transcription Methods 0.000 description 1
• 230000035897 transcription Effects 0.000 description 1
• 108091006106 transcriptional activators Proteins 0.000 description 1
• 108091008023 transcriptional regulators Proteins 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• 230000005945 translocation Effects 0.000 description 1
• 238000002054 transplantation Methods 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• INQOMBQAUSQDDS-FIBGUPNXSA-N trideuterio(iodo)methane Chemical compound [2H]C([2H])([2H])I INQOMBQAUSQDDS-FIBGUPNXSA-N 0.000 description 1
• YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
• 125000005455 trithianyl group Chemical group 0.000 description 1
• 229910052722 tritium Inorganic materials 0.000 description 1
• 210000004881 tumor cell Anatomy 0.000 description 1
• 230000004614 tumor growth Effects 0.000 description 1
• 241000701161 unidentified adenovirus Species 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 229920002554 vinyl polymer Polymers 0.000 description 1
• 230000009385 viral infection Effects 0.000 description 1
• 230000003612 virological effect Effects 0.000 description 1