PT3103802T - Novo composto de pirrolopirimidina ou seu sal, composição farmacêutica que o contém, especialmente agente para prevenção e/ou tratamento de tumores etc. com base no efeito inibidor de nae - Google Patents

Info

Publication number

PT3103802T

PT3103802T PT158113415T PT15811341T PT3103802T PT 3103802 T PT3103802 T PT 3103802T PT 158113415 T PT158113415 T PT 158113415T PT 15811341 T PT15811341 T PT 15811341T PT 3103802 T PT3103802 T PT 3103802T

Authority

PT

Portugal

Prior art keywords

group

ethynyl

amino

methyl

pyrrolo

Prior art date

2014-06-24

Links

• Espacenet
• Global Dossier
• Discuss

• -1 pyrrolopyrimidine compound Chemical class 0.000 title claims description 312
• 150000003839 salts Chemical class 0.000 title claims description 56
• 239000008194 pharmaceutical composition Substances 0.000 title claims description 4
• 206010028980 Neoplasm Diseases 0.000 title description 37
• 230000002401 inhibitory effect Effects 0.000 title description 30
• 230000002265 prevention Effects 0.000 title description 3
• 150000001875 compounds Chemical class 0.000 claims description 539
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 101
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 83
• 229910052757 nitrogen Inorganic materials 0.000 claims description 73
• 125000005842 heteroatom Chemical group 0.000 claims description 70
• 229910052760 oxygen Inorganic materials 0.000 claims description 63
• 229910052717 sulfur Inorganic materials 0.000 claims description 62
• 125000001424 substituent group Chemical group 0.000 claims description 58
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 56
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 56
• 125000002950 monocyclic group Chemical group 0.000 claims description 48
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 47
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 42
• 229910052736 halogen Inorganic materials 0.000 claims description 41
• 150000002367 halogens Chemical class 0.000 claims description 39
• 125000002619 bicyclic group Chemical group 0.000 claims description 38
• JJTNLWSCFYERCK-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine Chemical compound N1=CN=C2NC=CC2=C1 JJTNLWSCFYERCK-UHFFFAOYSA-N 0.000 claims description 33
• 125000003277 amino group Chemical group 0.000 claims description 31
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
• 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 29
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 27
• 229920006395 saturated elastomer Polymers 0.000 claims description 26
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 25
• 125000006580 bicyclic heterocycloalkyl group Chemical group 0.000 claims description 24
• 229910052739 hydrogen Inorganic materials 0.000 claims description 24
• 125000006578 monocyclic heterocycloalkyl group Chemical group 0.000 claims description 24
• 239000001257 hydrogen Substances 0.000 claims description 23
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 21
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 21
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 20
• 150000002431 hydrogen Chemical group 0.000 claims description 18
• 125000001153 fluoro group Chemical group F* 0.000 claims description 16
• 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 claims description 15
• 239000011737 fluorine Chemical group 0.000 claims description 15
• 229910052731 fluorine Inorganic materials 0.000 claims description 15
• 125000005549 heteroarylene group Chemical group 0.000 claims description 14
• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 14
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 13
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 12
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 11
• 125000004414 alkyl thio group Chemical group 0.000 claims description 11
• 125000002393 azetidinyl group Chemical group 0.000 claims description 11
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 11
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 11
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 11
• 125000004076 pyridyl group Chemical group 0.000 claims description 8
• 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 7
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
• 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 7
• 125000003282 alkyl amino group Chemical group 0.000 claims description 6
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 6
• 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 6
• 125000002757 morpholinyl group Chemical group 0.000 claims description 6
• 125000003386 piperidinyl group Chemical group 0.000 claims description 6
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 6
• MNLVCBKWEVXHGE-UHFFFAOYSA-N [CH]1[CH]CC[CH]1 Chemical group [CH]1[CH]CC[CH]1 MNLVCBKWEVXHGE-UHFFFAOYSA-N 0.000 claims description 5
• 125000000732 arylene group Chemical group 0.000 claims description 5
• 239000003112 inhibitor Substances 0.000 claims description 5
• 125000001624 naphthyl group Chemical group 0.000 claims description 5
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 4
• RAAZTGRWNXJQSP-WVSUBDOOSA-N 4-amino-5-[2-[2,6-difluoro-4-(methylamino)phenyl]ethynyl]-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1F)NC)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O RAAZTGRWNXJQSP-WVSUBDOOSA-N 0.000 claims description 4
• 239000002246 antineoplastic agent Substances 0.000 claims description 4
• 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims description 4
• 125000005843 halogen group Chemical group 0.000 claims description 4
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 4
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 3
• UUVOYHZELZARCP-NVQRDWNXSA-N 4-amino-5-[2-(4-amino-2,6-difluorophenyl)ethynyl]-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1F)N)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O UUVOYHZELZARCP-NVQRDWNXSA-N 0.000 claims description 3
• KDNFEVNQXVBGJN-FIAVLUJFSA-N 4-amino-5-[2-[2,6-difluoro-4-[(3R)-3-fluoropyrrolidin-1-yl]phenyl]ethynyl]-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1F)N1C[C@@H](CC1)F)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O KDNFEVNQXVBGJN-FIAVLUJFSA-N 0.000 claims description 3
• YUULHULMUJGTSP-ZDXOVATRSA-N 4-amino-5-[2-[2-(cyclopropylmethoxy)-6-fluorophenyl]ethynyl]-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1F)OCC1CC1)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O YUULHULMUJGTSP-ZDXOVATRSA-N 0.000 claims description 3
• MQXXNVWXDNYFCB-UVLLPENVSA-N 8-[2-[4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidin-5-yl]ethynyl]-7-fluoro-4-methyl-2,3-dihydro-1,4-benzoxazine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=2N(CCOC=21)C)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O MQXXNVWXDNYFCB-UVLLPENVSA-N 0.000 claims description 3
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
• 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 3
• 125000005476 oxopyrrolidinyl group Chemical group 0.000 claims description 3
• DITGIGCVAZTXKR-LZQZEXGQSA-N 4-amino-7-[(1R,4R,5S)-4,5-dihydroxy-3-[(sulfamoylamino)methyl]cyclopent-2-en-1-yl]-5-[2-(2-fluoro-6-methylsulfanylphenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1SC)F)[C@@H]1C=C([C@H]([C@H]1O)O)CNS(N)(=O)=O DITGIGCVAZTXKR-LZQZEXGQSA-N 0.000 claims description 2
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
• WBPQVBAZRMMAJE-NVQRDWNXSA-N 4-amino-5-[2-(2,6-difluorophenyl)ethynyl]-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1F)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O WBPQVBAZRMMAJE-NVQRDWNXSA-N 0.000 claims 1
• TZELMHYYCBRWPU-SNTIZLKRSA-N 4-amino-7-[(1R,2S,3R,4R)-2,3-dihydroxy-4-[(sulfamoylamino)methyl]cyclopentyl]-5-[2-(2-fluoro-6-methylsulfanylphenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1SC)F)[C@H]1[C@@H]([C@@H]([C@H](C1)CNS(N)(=O)=O)O)O TZELMHYYCBRWPU-SNTIZLKRSA-N 0.000 claims 1
• 239000004480 active ingredient Substances 0.000 claims 1
• 238000005160 1H NMR spectroscopy Methods 0.000 description 276
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 235
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 198
• 238000003786 synthesis reaction Methods 0.000 description 183
• 230000015572 biosynthetic process Effects 0.000 description 178
• 239000002904 solvent Substances 0.000 description 135
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 120
• 239000000243 solution Substances 0.000 description 94
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 90
• 238000006243 chemical reaction Methods 0.000 description 89
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 80
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 78
• BIFLARAADMSAQE-UHFFFAOYSA-N 2-ethynyl-1,3-difluorobenzene Chemical compound FC1=CC=CC(F)=C1C#C BIFLARAADMSAQE-UHFFFAOYSA-N 0.000 description 77
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 75
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 72
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 60
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 56
• 238000003756 stirring Methods 0.000 description 56
• 239000000203 mixture Substances 0.000 description 55
• 235000002639 sodium chloride Nutrition 0.000 description 53
• 238000000034 method Methods 0.000 description 47
• 238000010898 silica gel chromatography Methods 0.000 description 46
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 40
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 37
• 239000012044 organic layer Substances 0.000 description 36
• MCZUXEWWARACSP-UHFFFAOYSA-N 1-ethynylnaphthalene Chemical compound C1=CC=C2C(C#C)=CC=CC2=C1 MCZUXEWWARACSP-UHFFFAOYSA-N 0.000 description 31
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 30
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 29
• 210000004027 cell Anatomy 0.000 description 29
• 238000012360 testing method Methods 0.000 description 29
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 28
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 28
• UIOAYOIJMYMOEU-UHFFFAOYSA-N 2-fluoro-6-methoxybenzaldehyde Chemical compound COC1=CC=CC(F)=C1C=O UIOAYOIJMYMOEU-UHFFFAOYSA-N 0.000 description 26
• 239000007787 solid Substances 0.000 description 26
• 238000000926 separation method Methods 0.000 description 25
• 102000038427 NEDD8-activating enzyme E1 Human genes 0.000 description 23
• 108091007790 NEDD8-activating enzyme E1 Proteins 0.000 description 23
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 23
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 23
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 20
• 238000004821 distillation Methods 0.000 description 20
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 19
• 229910052938 sodium sulfate Inorganic materials 0.000 description 19
• 235000011152 sodium sulphate Nutrition 0.000 description 19
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 18
• 239000002585 base Substances 0.000 description 18
• 239000010410 layer Substances 0.000 description 18
• 238000004519 manufacturing process Methods 0.000 description 18
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 18
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 17
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 16
• 230000037396 body weight Effects 0.000 description 16
• 125000006239 protecting group Chemical group 0.000 description 16
• 230000002829 reductive effect Effects 0.000 description 16
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 15
• YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 15
• 239000012267 brine Substances 0.000 description 15
• 230000035484 reaction time Effects 0.000 description 15
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
• 239000007864 aqueous solution Substances 0.000 description 14
• 239000003153 chemical reaction reagent Substances 0.000 description 14
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 13
• 101710167917 Carbonic anhydrase 2 Proteins 0.000 description 13
• 102100024633 Carbonic anhydrase 2 Human genes 0.000 description 13
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
• 238000001816 cooling Methods 0.000 description 13
• 239000000126 substance Substances 0.000 description 13
• QFGUZGATFHIPML-UHFFFAOYSA-N sulfamoyl carbamate Chemical compound NC(=O)OS(N)(=O)=O QFGUZGATFHIPML-UHFFFAOYSA-N 0.000 description 13
• 238000009835 boiling Methods 0.000 description 12
• 239000012295 chemical reaction liquid Substances 0.000 description 12
• 230000000052 comparative effect Effects 0.000 description 12
• 239000000047 product Substances 0.000 description 12
• 108090000623 proteins and genes Proteins 0.000 description 12
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 11
• 239000003795 chemical substances by application Substances 0.000 description 11
• 239000003921 oil Substances 0.000 description 11
• 239000000843 powder Substances 0.000 description 11
• 102000004169 proteins and genes Human genes 0.000 description 11
• MPUQHZXIXSTTDU-QXGSTGNESA-N sulfamic acid [(1S,2S,4R)-4-[4-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]-7-pyrrolo[2,3-d]pyrimidinyl]-2-hydroxycyclopentyl]methyl ester Chemical compound C1[C@H](O)[C@H](COS(=O)(=O)N)C[C@H]1N1C2=NC=NC(N[C@@H]3C4=CC=CC=C4CC3)=C2C=C1 MPUQHZXIXSTTDU-QXGSTGNESA-N 0.000 description 11
• WTCQOVMJLJMLCQ-UHFFFAOYSA-N 2-bromo-5-phenylmethoxypyrimidine Chemical compound C1=NC(Br)=NC=C1OCC1=CC=CC=C1 WTCQOVMJLJMLCQ-UHFFFAOYSA-N 0.000 description 10
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 10
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 10
• 102100031911 NEDD8 Human genes 0.000 description 10
• 101150107958 NEDD8 gene Proteins 0.000 description 10
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
• GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 10
• 235000017557 sodium bicarbonate Nutrition 0.000 description 10
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 10
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 9
• 125000004432 carbon atom Chemical group C* 0.000 description 9
• 239000003054 catalyst Substances 0.000 description 9
• 238000010511 deprotection reaction Methods 0.000 description 9
• 210000004881 tumor cell Anatomy 0.000 description 9
• SYIVPXCHFAUXCL-UHFFFAOYSA-N 4-(4-ethynyl-3,5-difluorophenyl)morpholine Chemical compound FC1=C(C#C)C(F)=CC(N2CCOCC2)=C1 SYIVPXCHFAUXCL-UHFFFAOYSA-N 0.000 description 8
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
• 239000002253 acid Substances 0.000 description 8
• 230000000694 effects Effects 0.000 description 8
• KZGWPHUWNWRTEP-UHFFFAOYSA-N ethynyl-tri(propan-2-yl)silane Chemical compound CC(C)[Si](C#C)(C(C)C)C(C)C KZGWPHUWNWRTEP-UHFFFAOYSA-N 0.000 description 8
• 230000005764 inhibitory process Effects 0.000 description 8
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
• UFOVFJAVNWOGCS-UHFFFAOYSA-N C(C1=CC=CC=C1)OC=1C=NC(=NC=1)C#C[Si](C(C)C)(C(C)C)C(C)C Chemical compound C(C1=CC=CC=C1)OC=1C=NC(=NC=1)C#C[Si](C(C)C)(C(C)C)C(C)C UFOVFJAVNWOGCS-UHFFFAOYSA-N 0.000 description 7
• 238000006751 Mitsunobu reaction Methods 0.000 description 7
• 235000019270 ammonium chloride Nutrition 0.000 description 7
• 201000011510 cancer Diseases 0.000 description 7
• 238000001914 filtration Methods 0.000 description 7
• HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 7
• XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 7
• 229910000027 potassium carbonate Inorganic materials 0.000 description 7
• 239000011780 sodium chloride Substances 0.000 description 7
• 230000004614 tumor growth Effects 0.000 description 7
• OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 6
• NOPWUXRFETZTQG-UHFFFAOYSA-N 2-ethynyl-1,3,5-trifluorobenzene Chemical compound FC1=CC(F)=C(C#C)C(F)=C1 NOPWUXRFETZTQG-UHFFFAOYSA-N 0.000 description 6
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 6
• UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 6
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 6
• 206010039491 Sarcoma Diseases 0.000 description 6
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
• 125000000217 alkyl group Chemical group 0.000 description 6
• 150000001413 amino acids Chemical class 0.000 description 6
• 230000010261 cell growth Effects 0.000 description 6
• 239000007809 chemical reaction catalyst Substances 0.000 description 6
• 239000002552 dosage form Substances 0.000 description 6
• 201000005787 hematologic cancer Diseases 0.000 description 6
• 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 6
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
• 238000002360 preparation method Methods 0.000 description 6
• VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 6
• 238000000746 purification Methods 0.000 description 6
• 239000000758 substrate Substances 0.000 description 6
• CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical compound C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 6
• YBADLXQNJCMBKR-UHFFFAOYSA-N (4-nitrophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C([N+]([O-])=O)C=C1 YBADLXQNJCMBKR-UHFFFAOYSA-N 0.000 description 5
• RBLZCFSDCQHTGF-UHFFFAOYSA-N 2-ethylsulfanyl-6-fluoro-4-pyrrolidin-1-ylbenzaldehyde Chemical compound C(C)SC1=C(C=O)C(=CC(=C1)N1CCCC1)F RBLZCFSDCQHTGF-UHFFFAOYSA-N 0.000 description 5
• BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 5
• HGAIPYBAKIPQNV-UHFFFAOYSA-N 3-[(4-iodophenoxy)methyl]pyridine Chemical compound C1=CC(I)=CC=C1OCC1=CC=CN=C1 HGAIPYBAKIPQNV-UHFFFAOYSA-N 0.000 description 5
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 5
• 238000001061 Dunnett's test Methods 0.000 description 5
• 102000004190 Enzymes Human genes 0.000 description 5
• 108090000790 Enzymes Proteins 0.000 description 5
• 208000017604 Hodgkin disease Diseases 0.000 description 5
• 101000939348 Homo sapiens NEDD8-activating enzyme E1 regulatory subunit Proteins 0.000 description 5
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
• 241000699670 Mus sp. Species 0.000 description 5
• 238000006161 Suzuki-Miyaura coupling reaction Methods 0.000 description 5
• 238000002835 absorbance Methods 0.000 description 5
• 230000000259 anti-tumor effect Effects 0.000 description 5
• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 5
• 238000004440 column chromatography Methods 0.000 description 5
• 230000021615 conjugation Effects 0.000 description 5
• 238000005859 coupling reaction Methods 0.000 description 5
• 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 5
• 239000003814 drug Substances 0.000 description 5
• 238000001035 drying Methods 0.000 description 5
• 230000002255 enzymatic effect Effects 0.000 description 5
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
• 230000012010 growth Effects 0.000 description 5
• 238000002347 injection Methods 0.000 description 5
• 239000007924 injection Substances 0.000 description 5
• 208000019420 lymphoid neoplasm Diseases 0.000 description 5
• 229940098779 methanesulfonic acid Drugs 0.000 description 5
• VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 5
• 230000002633 protecting effect Effects 0.000 description 5
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
• LIIIRHQRQZIIRT-XLPZGREQSA-N (2r,3s,5r)-5-(4-amino-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-2-(hydroxymethyl)oxolan-3-ol Chemical compound C1=C(I)C=2C(N)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 LIIIRHQRQZIIRT-XLPZGREQSA-N 0.000 description 4
• GEADKCNVLLSIOV-UHFFFAOYSA-N 1-ethoxy-2-ethynyl-3-fluorobenzene Chemical compound C(C)OC1=C(C(=CC=C1)F)C#C GEADKCNVLLSIOV-UHFFFAOYSA-N 0.000 description 4
• GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
• QEBITPOSBYZLCY-UHFFFAOYSA-N 2-(4,6-dichloropyrimidin-5-yl)acetaldehyde Chemical compound ClC1=NC=NC(Cl)=C1CC=O QEBITPOSBYZLCY-UHFFFAOYSA-N 0.000 description 4
• QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 4
• FZIBGCDUHZBOLA-UHFFFAOYSA-N 2-fluoro-6-hydroxybenzaldehyde Chemical compound OC1=CC=CC(F)=C1C=O FZIBGCDUHZBOLA-UHFFFAOYSA-N 0.000 description 4
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 4
• MRPWHFIXTXRELA-UHFFFAOYSA-N 7-ethynyl-2,3-dihydro-1-benzothiophene Chemical compound C(#C)C1=CC=CC2=C1SCC2 MRPWHFIXTXRELA-UHFFFAOYSA-N 0.000 description 4
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 4
• 206010009944 Colon cancer Diseases 0.000 description 4
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 4
• 208000021519 Hodgkin lymphoma Diseases 0.000 description 4
• 208000010747 Hodgkins lymphoma Diseases 0.000 description 4
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 4
• 102100029781 NEDD8-activating enzyme E1 regulatory subunit Human genes 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
• 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 4
• 210000001744 T-lymphocyte Anatomy 0.000 description 4
• 229910021529 ammonia Inorganic materials 0.000 description 4
• 239000012131 assay buffer Substances 0.000 description 4
• 208000029742 colonic neoplasm Diseases 0.000 description 4
• 239000000287 crude extract Substances 0.000 description 4
• 239000012043 crude product Substances 0.000 description 4
• 150000002170 ethers Chemical class 0.000 description 4
• NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 4
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 4
• 150000002430 hydrocarbons Chemical group 0.000 description 4
• 238000004020 luminiscence type Methods 0.000 description 4
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
• 239000011259 mixed solution Substances 0.000 description 4
• KCAURZCKAUWSJP-UHFFFAOYSA-N n-(1-aza-4-azoniabicyclo[2.2.2]octan-4-ylsulfonyl)-1-[(2-methylpropan-2-yl)oxy]methanimidate Chemical compound C1CN2CC[N+]1(S(=O)(=O)/N=C([O-])/OC(C)(C)C)CC2 KCAURZCKAUWSJP-UHFFFAOYSA-N 0.000 description 4
• 239000012038 nucleophile Substances 0.000 description 4
• 239000002674 ointment Substances 0.000 description 4
• 239000003880 polar aprotic solvent Substances 0.000 description 4
• 239000002244 precipitate Substances 0.000 description 4
• 239000002243 precursor Substances 0.000 description 4
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
• 230000001012 protector Effects 0.000 description 4
• 238000000638 solvent extraction Methods 0.000 description 4
• 239000003381 stabilizer Substances 0.000 description 4
• 239000000829 suppository Substances 0.000 description 4
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
• 229910052723 transition metal Inorganic materials 0.000 description 4
• 150000003624 transition metals Chemical class 0.000 description 4
• PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 4
• VGYVQKBPAHWCAL-MRVPVSSYSA-N (3R)-1-(4-ethynyl-3,5-difluorophenyl)-3-fluoropyrrolidine Chemical compound C(#C)C1=C(C=C(C=C1F)N1C[C@@H](CC1)F)F VGYVQKBPAHWCAL-MRVPVSSYSA-N 0.000 description 3
• DQYSWHBGSBIBDS-SECBINFHSA-N (3R)-1-(4-ethynyl-3,5-difluorophenyl)pyrrolidin-3-ol Chemical compound C(#C)C1=C(C=C(C=C1F)N1C[C@@H](CC1)O)F DQYSWHBGSBIBDS-SECBINFHSA-N 0.000 description 3
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 3
• GFPWXTIGISYRKF-UHFFFAOYSA-N 1-(3-ethylsulfonyl-4-ethynyl-5-fluorophenyl)pyrrolidine Chemical compound C(C)S(=O)(=O)C=1C=C(C=C(C=1C#C)F)N1CCCC1 GFPWXTIGISYRKF-UHFFFAOYSA-N 0.000 description 3
• ZNRRQPSAZGIOQP-UHFFFAOYSA-N 1-(4-ethynyl-3,5-difluorophenyl)piperidine Chemical compound C(#C)C1=C(C=C(C=C1F)N1CCCCC1)F ZNRRQPSAZGIOQP-UHFFFAOYSA-N 0.000 description 3
• OOSLYJREEAOCHM-UHFFFAOYSA-N 1-ethoxy-2-ethynyl-3-methoxybenzene Chemical compound C(C)OC1=C(C(=CC=C1)OC)C#C OOSLYJREEAOCHM-UHFFFAOYSA-N 0.000 description 3
• GWZPKIXRLCPYTH-UHFFFAOYSA-N 1-ethylsulfanyl-2-ethynyl-3-fluorobenzene Chemical compound C(C)SC1=C(C(=CC=C1)F)C#C GWZPKIXRLCPYTH-UHFFFAOYSA-N 0.000 description 3
• MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 3
• ROAQMGJHSNIROA-UHFFFAOYSA-N 2,6-difluoro-4-hydroxybenzaldehyde Chemical compound OC1=CC(F)=C(C=O)C(F)=C1 ROAQMGJHSNIROA-UHFFFAOYSA-N 0.000 description 3
• GKPSFHUCVWCEMY-UHFFFAOYSA-N 2,6-difluoro-4-pyrrolidin-1-ylbenzaldehyde Chemical compound FC1=C(C=O)C(=CC(=C1)N1CCCC1)F GKPSFHUCVWCEMY-UHFFFAOYSA-N 0.000 description 3
• UKKKRIKTERNFDQ-UHFFFAOYSA-N 2-(2-methylphenyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3-thiazole Chemical compound CC1=CC=CC=C1C1=NC(B2OC(C)(C)C(C)(C)O2)=CS1 UKKKRIKTERNFDQ-UHFFFAOYSA-N 0.000 description 3
• 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 3
• ICZNLPFOXUENMQ-UHFFFAOYSA-N 2-ethylsulfanyl-6-fluorobenzaldehyde Chemical compound C(C)SC1=C(C=O)C(=CC=C1)F ICZNLPFOXUENMQ-UHFFFAOYSA-N 0.000 description 3
• LWKGWSYFWKBJDL-UHFFFAOYSA-N 2-ethynyl-1-fluoro-3-methoxybenzene Chemical compound COC1=CC=CC(F)=C1C#C LWKGWSYFWKBJDL-UHFFFAOYSA-N 0.000 description 3
• HVMMQNBSEQJIGE-UHFFFAOYSA-N 2-ethynyl-1-fluoro-3-methylsulfanylbenzene Chemical compound C(#C)C1=C(C=CC=C1F)SC HVMMQNBSEQJIGE-UHFFFAOYSA-N 0.000 description 3
• HRADVHZVMOMEPU-UHFFFAOYSA-N 3-iodopyrrolidine-2,5-dione Chemical compound IC1CC(=O)NC1=O HRADVHZVMOMEPU-UHFFFAOYSA-N 0.000 description 3
• PYGJHYWDGWUBBF-UHFFFAOYSA-N 4-(3-ethoxy-4-ethynyl-5-fluorophenyl)morpholine Chemical compound C(C)OC=1C=C(C=C(C=1C#C)F)N1CCOCC1 PYGJHYWDGWUBBF-UHFFFAOYSA-N 0.000 description 3
• LTWVILIXPCHMFT-UHFFFAOYSA-N 4-(4-ethynyl-3,5-difluorophenyl)thiomorpholine Chemical compound C(#C)C1=C(C=C(C=C1F)N1CCSCC1)F LTWVILIXPCHMFT-UHFFFAOYSA-N 0.000 description 3
• NKPXAZHQXLCJFN-UHFFFAOYSA-N 4-ethynyl-3-fluoro-2,5-dimethoxypyridine Chemical compound C(#C)C1=C(C(=NC=C1OC)OC)F NKPXAZHQXLCJFN-UHFFFAOYSA-N 0.000 description 3
• JPTXTLMYFHNUMP-UHFFFAOYSA-N 7-fluoro-4-methyl-2,3-dihydro-1,4-benzoxazine-8-carbaldehyde Chemical compound FC1=C(C2=C(N(CCO2)C)C=C1)C=O JPTXTLMYFHNUMP-UHFFFAOYSA-N 0.000 description 3
• FIXLCVUVXUGHLC-UHFFFAOYSA-N 8-ethynyl-7-fluoro-4-methyl-2,3-dihydro-1,4-benzoxazine Chemical compound C(#C)C1=C(C=CC=2N(CCOC=21)C)F FIXLCVUVXUGHLC-UHFFFAOYSA-N 0.000 description 3
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 3
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 3
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 3
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
• 239000007995 HEPES buffer Substances 0.000 description 3
• 101000644669 Homo sapiens NEDD8-conjugating enzyme Ubc12 Proteins 0.000 description 3
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 3
• 241001465754 Metazoa Species 0.000 description 3
• 208000034578 Multiple myelomas Diseases 0.000 description 3
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 3
• 206010035226 Plasma cell myeloma Diseases 0.000 description 3
• 208000033014 Plasma cell tumor Diseases 0.000 description 3
• 208000007452 Plasmacytoma Diseases 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• 206010060862 Prostate cancer Diseases 0.000 description 3
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 3
• 208000000453 Skin Neoplasms Diseases 0.000 description 3
• 208000021712 Soft tissue sarcoma Diseases 0.000 description 3
• 238000003477 Sonogashira cross-coupling reaction Methods 0.000 description 3
• 229930006000 Sucrose Natural products 0.000 description 3
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
• 102000003436 UBA3 Human genes 0.000 description 3
• 108060008744 UBA3 Proteins 0.000 description 3
• ODTWWJKXEQAEDH-QYVSTXNMSA-N [(3ar,4r,6r,6ar)-4-(4-amino-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methanol Chemical compound C1=C(I)C2=C(N)N=CN=C2N1[C@@H]1O[C@H](CO)[C@H]2OC(C)(C)O[C@H]21 ODTWWJKXEQAEDH-QYVSTXNMSA-N 0.000 description 3
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
• 230000004913 activation Effects 0.000 description 3
• 230000002411 adverse Effects 0.000 description 3
• 150000001298 alcohols Chemical class 0.000 description 3
• HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 3
• 229910052786 argon Inorganic materials 0.000 description 3
• 230000002238 attenuated effect Effects 0.000 description 3
• 150000001639 boron compounds Chemical class 0.000 description 3
• 239000000872 buffer Substances 0.000 description 3
• BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 3
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
• 229910000024 caesium carbonate Inorganic materials 0.000 description 3
• 230000008859 change Effects 0.000 description 3
• 239000007810 chemical reaction solvent Substances 0.000 description 3
• 239000003638 chemical reducing agent Substances 0.000 description 3
• 239000000460 chlorine Substances 0.000 description 3
• 229910052801 chlorine Inorganic materials 0.000 description 3
• UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 3
• 239000013078 crystal Substances 0.000 description 3
• 238000002425 crystallisation Methods 0.000 description 3
• 238000001514 detection method Methods 0.000 description 3
• HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 3
• 239000003937 drug carrier Substances 0.000 description 3
• 210000003743 erythrocyte Anatomy 0.000 description 3
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 3
• 238000000605 extraction Methods 0.000 description 3
• 239000000796 flavoring agent Substances 0.000 description 3
• RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 3
• 235000011187 glycerol Nutrition 0.000 description 3
• 230000009422 growth inhibiting effect Effects 0.000 description 3
• 108700021968 human NAE Proteins 0.000 description 3
• 229930195733 hydrocarbon Natural products 0.000 description 3
• 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 3
• 208000032839 leukemia Diseases 0.000 description 3
• 201000005202 lung cancer Diseases 0.000 description 3
• 208000020816 lung neoplasm Diseases 0.000 description 3
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 3
• 210000003519 mature b lymphocyte Anatomy 0.000 description 3
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
• 125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 3
• 210000000822 natural killer cell Anatomy 0.000 description 3
• 230000009527 neddylation Effects 0.000 description 3
• 150000002825 nitriles Chemical class 0.000 description 3
• 230000003287 optical effect Effects 0.000 description 3
• 201000008968 osteosarcoma Diseases 0.000 description 3
• 239000007800 oxidant agent Substances 0.000 description 3
• 230000001590 oxidative effect Effects 0.000 description 3
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 3
• 208000008443 pancreatic carcinoma Diseases 0.000 description 3
• QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 3
• 239000000825 pharmaceutical preparation Substances 0.000 description 3
• 125000004193 piperazinyl group Chemical group 0.000 description 3
• 208000010626 plasma cell neoplasm Diseases 0.000 description 3
• 239000013612 plasmid Substances 0.000 description 3
• LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 3
• 125000005493 quinolyl group Chemical group 0.000 description 3
• 239000000377 silicon dioxide Substances 0.000 description 3
• 201000000849 skin cancer Diseases 0.000 description 3
• 229910000029 sodium carbonate Inorganic materials 0.000 description 3
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
• 239000005720 sucrose Substances 0.000 description 3
• GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 3
• 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 3
• 125000001544 thienyl group Chemical group 0.000 description 3
• 241000701447 unidentified baculovirus Species 0.000 description 3
• 239000008096 xylene Substances 0.000 description 3
• UNKGVNOWNRNCPW-BHNWBGBOSA-N (1S,2R,4R)-4-(4-amino-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-2-(hydroxymethyl)cyclopentan-1-ol Chemical compound NC=1C2=C(N=CN=1)N(C=C2I)[C@@H]1C[C@@H]([C@H](C1)O)CO UNKGVNOWNRNCPW-BHNWBGBOSA-N 0.000 description 2
• UWYOIXWMJDGARH-SNVBAGLBSA-N (3R)-1-(3-ethylsulfonyl-4-ethynyl-5-fluorophenyl)-3-fluoropyrrolidine Chemical compound C(C)S(=O)(=O)C=1C=C(C=C(C=1C#C)F)N1C[C@@H](CC1)F UWYOIXWMJDGARH-SNVBAGLBSA-N 0.000 description 2
• JNCBIPYODLZPGD-LLVKDONJSA-N (3R)-1-(3-ethylsulfonyl-4-ethynyl-5-fluorophenyl)pyrrolidin-3-ol Chemical compound C(C)S(=O)(=O)C=1C=C(C=C(C=1C#C)F)N1C[C@@H](CC1)O JNCBIPYODLZPGD-LLVKDONJSA-N 0.000 description 2
• LOOJZGNBEXZLLJ-SNVBAGLBSA-N (3R)-1-(4-ethynyl-3,5-difluorophenyl)piperidin-3-ol Chemical compound C(#C)C1=C(C=C(C=C1F)N1C[C@@H](CCC1)O)F LOOJZGNBEXZLLJ-SNVBAGLBSA-N 0.000 description 2
• VGYVQKBPAHWCAL-QMMMGPOBSA-N (3S)-1-(4-ethynyl-3,5-difluorophenyl)-3-fluoropyrrolidine Chemical compound C(#C)C1=C(C=C(C=C1F)N1C[C@H](CC1)F)F VGYVQKBPAHWCAL-QMMMGPOBSA-N 0.000 description 2
• DQYSWHBGSBIBDS-VIFPVBQESA-N (3S)-1-(4-ethynyl-3,5-difluorophenyl)pyrrolidin-3-ol Chemical compound C(#C)C1=C(C=C(C=C1F)N1C[C@H](CC1)O)F DQYSWHBGSBIBDS-VIFPVBQESA-N 0.000 description 2
• CDDGNGVFPQRJJM-SCSAIBSYSA-N (3r)-3-fluoropyrrolidine Chemical compound F[C@@H]1CCNC1 CDDGNGVFPQRJJM-SCSAIBSYSA-N 0.000 description 2
• JHHZLHWJQPUNKB-SCSAIBSYSA-N (3r)-pyrrolidin-3-ol Chemical compound O[C@@H]1CCNC1 JHHZLHWJQPUNKB-SCSAIBSYSA-N 0.000 description 2
• SQHSJJGGWYIFCD-UHFFFAOYSA-N (e)-1-diazonio-1-dimethoxyphosphorylprop-1-en-2-olate Chemical compound COP(=O)(OC)C(\[N+]#N)=C(\C)[O-] SQHSJJGGWYIFCD-UHFFFAOYSA-N 0.000 description 2
• GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
• ABADUMLIAZCWJD-UHFFFAOYSA-N 1,3-dioxole Chemical compound C1OC=CO1 ABADUMLIAZCWJD-UHFFFAOYSA-N 0.000 description 2
• JLBFLZFFGYGZGN-UHFFFAOYSA-N 1,4-diazabicyclo[2.2.2]octane;hydrochloride Chemical compound Cl.C1CN2CCN1CC2 JLBFLZFFGYGZGN-UHFFFAOYSA-N 0.000 description 2
• BAYKAWVVKMGXPR-UHFFFAOYSA-N 1-(3-ethoxy-4-ethynyl-5-fluorophenyl)piperidine Chemical compound C(C)OC=1C=C(C=C(C=1C#C)F)N1CCCCC1 BAYKAWVVKMGXPR-UHFFFAOYSA-N 0.000 description 2
• BQZTXOSSBDPOIY-UHFFFAOYSA-N 1-(4-ethynyl-3,5-difluorophenyl)-4-methylpiperazine Chemical compound C(#C)C1=C(C=C(C=C1F)N1CCN(CC1)C)F BQZTXOSSBDPOIY-UHFFFAOYSA-N 0.000 description 2
• WMCFTFBYZSEVHU-UHFFFAOYSA-N 1-(4-ethynyl-3,5-difluorophenyl)azetidin-3-ol Chemical compound C(#C)C1=C(C=C(C=C1F)N1CC(C1)O)F WMCFTFBYZSEVHU-UHFFFAOYSA-N 0.000 description 2
• KKXAYVCXNPNCPT-UHFFFAOYSA-N 1-(4-ethynyl-3,5-difluorophenyl)azetidine Chemical compound C(#C)C1=C(C=C(C=C1F)N1CCC1)F KKXAYVCXNPNCPT-UHFFFAOYSA-N 0.000 description 2
• LOOJZGNBEXZLLJ-UHFFFAOYSA-N 1-(4-ethynyl-3,5-difluorophenyl)piperidin-3-ol Chemical compound C(#C)C1=C(C=C(C=C1F)N1CC(CCC1)O)F LOOJZGNBEXZLLJ-UHFFFAOYSA-N 0.000 description 2
• USFHGIYIWMMDCO-UHFFFAOYSA-N 1-(4-ethynyl-3,5-difluorophenyl)piperidin-4-ol Chemical compound C(#C)C1=C(C=C(C=C1F)N1CCC(CC1)O)F USFHGIYIWMMDCO-UHFFFAOYSA-N 0.000 description 2
• OGEQKPGIUYYMGL-UHFFFAOYSA-N 1-(4-ethynyl-3,5-difluorophenyl)piperidin-4-one Chemical compound C(#C)C1=C(C=C(C=C1F)N1CCC(CC1)=O)F OGEQKPGIUYYMGL-UHFFFAOYSA-N 0.000 description 2
• XIMZBPRCBHPIQB-UHFFFAOYSA-N 1-(4-ethynyl-3,5-difluorophenyl)pyrrolidin-2-one Chemical compound C(#C)C1=C(C=C(C=C1F)N1C(CCC1)=O)F XIMZBPRCBHPIQB-UHFFFAOYSA-N 0.000 description 2
• MXOYUCHTOSQQRG-UHFFFAOYSA-N 1-(4-ethynyl-3,5-difluorophenyl)pyrrolidine Chemical compound C(#C)C1=C(C=C(C=C1F)N1CCCC1)F MXOYUCHTOSQQRG-UHFFFAOYSA-N 0.000 description 2
• BPLUVKLLEKZXHO-UHFFFAOYSA-N 1-(4-ethynyl-3,5-difluorophenyl)pyrrolidine-3-carboxylic acid Chemical compound C(#C)C1=C(C=C(C=C1F)N1CC(CC1)C(=O)O)F BPLUVKLLEKZXHO-UHFFFAOYSA-N 0.000 description 2
• IGONYTISVYYMOU-UHFFFAOYSA-N 1-(4-ethynyl-3-methylsulfanylphenyl)piperidine Chemical compound C(#C)C1=C(C=C(C=C1)N1CCCCC1)SC IGONYTISVYYMOU-UHFFFAOYSA-N 0.000 description 2
• NMCYRLZKBDGGLJ-UHFFFAOYSA-N 1-(cyclopropylmethoxy)-2-ethynyl-3-fluorobenzene Chemical compound C1(CC1)COC1=C(C(=CC=C1)F)C#C NMCYRLZKBDGGLJ-UHFFFAOYSA-N 0.000 description 2
• YAQWSKDPRAWKQS-UHFFFAOYSA-N 1-(cyclopropylmethoxy)-3-fluoro-2-iodobenzene Chemical compound C1(CC1)COC1=C(C(=CC=C1)F)I YAQWSKDPRAWKQS-UHFFFAOYSA-N 0.000 description 2
• YEFVJGSFDLFBIJ-UHFFFAOYSA-N 1-[(3,4-dimethylphenyl)methyl]-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole Chemical compound CC=1C=C(CN2N=CC(=C2)B2OC(C(O2)(C)C)(C)C)C=CC=1C YEFVJGSFDLFBIJ-UHFFFAOYSA-N 0.000 description 2
• VJSYVQIDZFVGHB-UHFFFAOYSA-N 1-[(4-ethynyl-3,5-difluorophenoxy)methyl]pyrazole Chemical compound C(#C)C1=C(C=C(OCN2N=CC=C2)C=C1F)F VJSYVQIDZFVGHB-UHFFFAOYSA-N 0.000 description 2
• ZVPORPUUZXIPEF-UHFFFAOYSA-N 1-benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole Chemical compound O1C(C)(C)C(C)(C)OB1C1=CN(CC=2C=CC=CC=2)N=C1 ZVPORPUUZXIPEF-UHFFFAOYSA-N 0.000 description 2
• WOXZDKIPMCBQJL-UHFFFAOYSA-N 1-chloro-2-ethynyl-3-fluorobenzene Chemical compound FC1=CC=CC(Cl)=C1C#C WOXZDKIPMCBQJL-UHFFFAOYSA-N 0.000 description 2
• LXURFIWAXPPULA-UHFFFAOYSA-N 1-ethoxy-2-ethynyl-3,5-difluorobenzene Chemical compound C(C)OC1=C(C(=CC(=C1)F)F)C#C LXURFIWAXPPULA-UHFFFAOYSA-N 0.000 description 2
• MDHXXIUGBYAXFX-UHFFFAOYSA-N 1-ethylsulfanyl-2-ethynylbenzene Chemical compound C(C)SC1=C(C=CC=C1)C#C MDHXXIUGBYAXFX-UHFFFAOYSA-N 0.000 description 2
• ABEALTLRVQSSTL-UHFFFAOYSA-N 1-ethynyl-2-fluoro-4-phenylmethoxybenzene Chemical compound C(C1=CC=CC=C1)OC1=CC(=C(C=C1)C#C)F ABEALTLRVQSSTL-UHFFFAOYSA-N 0.000 description 2
• ZXJQAPVWLVJASW-UHFFFAOYSA-N 1-ethynyl-2-methoxy-4-phenylmethoxybenzene Chemical compound C1=C(C#C)C(OC)=CC(OCC=2C=CC=CC=2)=C1 ZXJQAPVWLVJASW-UHFFFAOYSA-N 0.000 description 2
• SHMLUCZEAQRHEX-UHFFFAOYSA-N 1-ethynyl-2-methylsulfanyl-4-phenylmethoxybenzene Chemical compound C(C1=CC=CC=C1)OC=1C=CC(=C(C=1)SC)C#C SHMLUCZEAQRHEX-UHFFFAOYSA-N 0.000 description 2
• NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 2
• GRKPUDXMIGTKMY-UHFFFAOYSA-N 2,6-difluoro-4-(pyrazol-1-ylmethoxy)benzaldehyde Chemical compound N1(N=CC=C1)COC1=CC(=C(C=O)C(=C1)F)F GRKPUDXMIGTKMY-UHFFFAOYSA-N 0.000 description 2
• QMWIMEBVJOZHAH-UHFFFAOYSA-N 2,6-difluoro-4-(triazol-2-ylmethoxy)benzaldehyde Chemical compound N=1N(N=CC=1)COC1=CC(=C(C=O)C(=C1)F)F QMWIMEBVJOZHAH-UHFFFAOYSA-N 0.000 description 2
• XLTBPFVUDIRJRR-UHFFFAOYSA-N 2,6-difluoro-4-phenylmethoxybenzaldehyde Chemical compound FC1=C(C=O)C(F)=CC(OCC=2C=CC=CC=2)=C1 XLTBPFVUDIRJRR-UHFFFAOYSA-N 0.000 description 2
• ZVWGNKVEHJFEMR-UHFFFAOYSA-N 2-(ethylamino)-6-fluorobenzaldehyde Chemical compound C(C)NC1=C(C=O)C(=CC=C1)F ZVWGNKVEHJFEMR-UHFFFAOYSA-N 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
• LUFUYUNUCJYRNQ-UHFFFAOYSA-N 2-[(4-ethynyl-3,5-difluorophenoxy)methyl]triazole Chemical compound C(#C)C1=C(C=C(OCN2N=CC=N2)C=C1F)F LUFUYUNUCJYRNQ-UHFFFAOYSA-N 0.000 description 2
• VHZCPJWEAMDEKL-UHFFFAOYSA-N 2-ethoxy-6-fluorobenzaldehyde Chemical compound CCOC1=CC=CC(F)=C1C=O VHZCPJWEAMDEKL-UHFFFAOYSA-N 0.000 description 2
• RCDGEAXHWDOTEQ-UHFFFAOYSA-N 2-ethoxy-6-methoxybenzaldehyde Chemical compound CCOC1=CC=CC(OC)=C1C=O RCDGEAXHWDOTEQ-UHFFFAOYSA-N 0.000 description 2
• OPNRAZUYUKXLMF-SECBINFHSA-N 2-ethylsulfanyl-6-fluoro-4-[(3R)-3-fluoropyrrolidin-1-yl]benzaldehyde Chemical compound C(C)SC1=C(C=O)C(=CC(=C1)N1C[C@@H](CC1)F)F OPNRAZUYUKXLMF-SECBINFHSA-N 0.000 description 2
• FFAXFBNIWVAYLA-SNVBAGLBSA-N 2-ethylsulfanyl-6-fluoro-4-[(3R)-3-hydroxypyrrolidin-1-yl]benzaldehyde Chemical compound C(C)SC1=C(C=O)C(=CC(=C1)N1C[C@@H](CC1)O)F FFAXFBNIWVAYLA-SNVBAGLBSA-N 0.000 description 2
• DQSBFSXPCPSOHN-SECBINFHSA-N 2-ethylsulfonyl-6-fluoro-4-[(3R)-3-fluoropyrrolidin-1-yl]benzaldehyde Chemical compound C(C)S(=O)(=O)C1=C(C=O)C(=CC(=C1)N1C[C@@H](CC1)F)F DQSBFSXPCPSOHN-SECBINFHSA-N 0.000 description 2
• KYZPSTZAKDCVTM-SNVBAGLBSA-N 2-ethylsulfonyl-6-fluoro-4-[(3R)-3-hydroxypyrrolidin-1-yl]benzaldehyde Chemical compound C(C)S(=O)(=O)C1=C(C=O)C(=CC(=C1)N1C[C@@H](CC1)O)F KYZPSTZAKDCVTM-SNVBAGLBSA-N 0.000 description 2
• BFQBJZYCVANZPQ-UHFFFAOYSA-N 2-ethynyl-1,3-difluoro-5-phenylmethoxybenzene Chemical compound C(C1=CC=CC=C1)OC=1C=C(C(=C(C=1)F)C#C)F BFQBJZYCVANZPQ-UHFFFAOYSA-N 0.000 description 2
• SDMBIXSWLMFUFH-UHFFFAOYSA-N 2-ethynyl-1,3-dimethoxybenzene Chemical compound COC1=CC=CC(OC)=C1C#C SDMBIXSWLMFUFH-UHFFFAOYSA-N 0.000 description 2
• WHRVBOSVGYCDJK-UHFFFAOYSA-N 2-ethynyl-1-fluoro-3-(2,2,2-trifluoroethoxy)benzene Chemical compound C(#C)C1=C(C=CC=C1OCC(F)(F)F)F WHRVBOSVGYCDJK-UHFFFAOYSA-N 0.000 description 2
• GUYNMBSUUDHKEH-UHFFFAOYSA-N 2-ethynyl-1-fluoro-3-propan-2-yloxybenzene Chemical compound C(#C)C1=C(C=CC=C1OC(C)C)F GUYNMBSUUDHKEH-UHFFFAOYSA-N 0.000 description 2
• XCXYBWSYXZHLIY-UHFFFAOYSA-N 2-ethynyl-1-fluoro-3-propoxybenzene Chemical compound CCCOc1cccc(F)c1C#C XCXYBWSYXZHLIY-UHFFFAOYSA-N 0.000 description 2
• ZSJJECYCEMGECK-UHFFFAOYSA-N 2-ethynyl-3-fluorobenzamide Chemical compound C(#C)C1=C(C(=O)N)C=CC=C1F ZSJJECYCEMGECK-UHFFFAOYSA-N 0.000 description 2
• RQWZVPXAHKROAN-UHFFFAOYSA-N 2-ethynyl-3-fluorobenzonitrile Chemical compound C(#C)C1=C(C#N)C=CC=C1F RQWZVPXAHKROAN-UHFFFAOYSA-N 0.000 description 2
• MMDLQUHOQNYVIQ-UHFFFAOYSA-N 2-ethynyl-5-phenylmethoxypyridine Chemical compound C(C1=CC=CC=C1)OC=1C=CC(=NC=1)C#C MMDLQUHOQNYVIQ-UHFFFAOYSA-N 0.000 description 2
• UFKBBAIPDBFSGZ-UHFFFAOYSA-N 2-ethynyl-5-phenylmethoxypyrimidine Chemical compound C(C1=CC=CC=C1)OC=1C=NC(=NC=1)C#C UFKBBAIPDBFSGZ-UHFFFAOYSA-N 0.000 description 2
• QNQWATWCTLTYSE-UHFFFAOYSA-N 2-fluoro-6-(2,2,2-trifluoroethoxy)benzaldehyde Chemical compound FC1=CC=CC(OCC(F)(F)F)=C1C=O QNQWATWCTLTYSE-UHFFFAOYSA-N 0.000 description 2
• YGOUXDFRAGLTTF-UHFFFAOYSA-N 2-fluoro-6-propan-2-yloxybenzaldehyde Chemical compound CC(C)OC1=CC=CC(F)=C1C=O YGOUXDFRAGLTTF-UHFFFAOYSA-N 0.000 description 2
• YJVZAUWNRCGXQP-UHFFFAOYSA-N 2-fluoro-6-propoxybenzaldehyde Chemical compound FC1=C(C=O)C(=CC=C1)OCCC YJVZAUWNRCGXQP-UHFFFAOYSA-N 0.000 description 2
• YRLORWPBJZEGBX-UHFFFAOYSA-N 3,4-dihydro-2h-1,4-benzoxazine Chemical group C1=CC=C2NCCOC2=C1 YRLORWPBJZEGBX-UHFFFAOYSA-N 0.000 description 2
• OOJYYKGLOFVXEZ-UHFFFAOYSA-N 3-(3-ethoxy-4-ethynyl-5-fluorophenyl)-8-oxa-3-azabicyclo[3.2.1]octane Chemical compound C(C)OC=1C=C(C=C(C=1C#C)F)N1CC2CCC(C1)O2 OOJYYKGLOFVXEZ-UHFFFAOYSA-N 0.000 description 2
• AONRRIJYMOGVRH-UHFFFAOYSA-N 3-(4-ethynyl-3,5-difluorophenyl)-8-oxa-3-azabicyclo[3.2.1]octane Chemical compound C(#C)C1=C(C=C(C=C1F)N1CC2CCC(C1)O2)F AONRRIJYMOGVRH-UHFFFAOYSA-N 0.000 description 2
• WBEJUEPTTKSYQB-UHFFFAOYSA-N 3-ethynyl-2,4-difluoropyridine Chemical compound FC1=CC=NC(F)=C1C#C WBEJUEPTTKSYQB-UHFFFAOYSA-N 0.000 description 2
• POUIGMGAMOFEIC-UHFFFAOYSA-N 3-ethynyl-2,4-dimethoxypyridine Chemical compound C(#C)C=1C(=NC=CC=1OC)OC POUIGMGAMOFEIC-UHFFFAOYSA-N 0.000 description 2
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
• NXVOJCPQURCECO-PTGPVQHPSA-N 4-[4-[2-[4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidin-5-yl]ethynyl]-3-ethoxy-5-fluorophenyl]morpholine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1F)N1CCOCC1)OCC)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O NXVOJCPQURCECO-PTGPVQHPSA-N 0.000 description 2
• KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 2
• CBWBJFJMNBPWAL-UHFFFAOYSA-N 4-chloro-5-iodo-7h-pyrrolo[2,3-d]pyrimidine Chemical compound ClC1=NC=NC2=C1C(I)=CN2 CBWBJFJMNBPWAL-UHFFFAOYSA-N 0.000 description 2
• SGHPKECKDATBEV-UHFFFAOYSA-N 4-ethynyl-3,5-difluoro-2-methoxypyridine Chemical compound C(#C)C1=C(C(=NC=C1F)OC)F SGHPKECKDATBEV-UHFFFAOYSA-N 0.000 description 2
• WOWNQTOCIULQGW-UHFFFAOYSA-N 4-ethynyl-3,5-difluoro-N-methylaniline Chemical compound C(#C)C1=C(C=C(NC)C=C1F)F WOWNQTOCIULQGW-UHFFFAOYSA-N 0.000 description 2
• CAOQOVWEQYKWOG-UHFFFAOYSA-N 4-ethynyl-3,5-difluorobenzonitrile Chemical compound C(#C)C1=C(C=C(C#N)C=C1F)F CAOQOVWEQYKWOG-UHFFFAOYSA-N 0.000 description 2
• MWCFKZOMBRUCFM-UHFFFAOYSA-N 4-ethynyl-3,5-difluorophenol Chemical compound C(#C)C1=C(C=C(C=C1F)O)F MWCFKZOMBRUCFM-UHFFFAOYSA-N 0.000 description 2
• LRUHEESTHRSJLT-UHFFFAOYSA-N 4-ethynyl-3-fluoro-5-methoxypyridine Chemical compound COC1=CN=CC(F)=C1C#C LRUHEESTHRSJLT-UHFFFAOYSA-N 0.000 description 2
• 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 2
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
• JLIKFINAWOCRMM-UHFFFAOYSA-N 8-(3-ethoxy-4-ethynyl-5-fluorophenyl)-3-oxa-8-azabicyclo[3.2.1]octane Chemical compound C(C)OC=1C=C(C=C(C=1C#C)F)N1C2COCC1CC2 JLIKFINAWOCRMM-UHFFFAOYSA-N 0.000 description 2
• CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 2
• DPBXVSNHCUAMSM-UHFFFAOYSA-N 8-(4-ethynyl-3,5-difluorophenyl)-3-oxa-8-azabicyclo[3.2.1]octane Chemical compound C(#C)C1=C(C=C(C=C1F)N1C2COCC1CC2)F DPBXVSNHCUAMSM-UHFFFAOYSA-N 0.000 description 2
• PBKFDEMENCIDDQ-UHFFFAOYSA-N 8-ethynylquinoline Chemical compound C1=CN=C2C(C#C)=CC=CC2=C1 PBKFDEMENCIDDQ-UHFFFAOYSA-N 0.000 description 2
• 206010000830 Acute leukaemia Diseases 0.000 description 2
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 2
• 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 2
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
• 208000003950 B-cell lymphoma Diseases 0.000 description 2
• KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 2
• 208000008720 Bone Marrow Neoplasms Diseases 0.000 description 2
• KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
• 206010006187 Breast cancer Diseases 0.000 description 2
• 208000026310 Breast neoplasm Diseases 0.000 description 2
• JIALYFAFTZXAFW-UHFFFAOYSA-N C(#C)C=1C=CC=C2CCCSC=12 Chemical compound C(#C)C=1C=CC=C2CCCSC=12 JIALYFAFTZXAFW-UHFFFAOYSA-N 0.000 description 2
• KZDMVZLHIFSDMH-UHFFFAOYSA-N C(C)(C)[Si](C#CC=1C=CC=C2CCCSC=12)(C(C)C)C(C)C Chemical compound C(C)(C)[Si](C#CC=1C=CC=C2CCCSC=12)(C(C)C)C(C)C KZDMVZLHIFSDMH-UHFFFAOYSA-N 0.000 description 2
• KTASQKTXUZWUGL-UHFFFAOYSA-N C(C1=CC=CC=C1)NC1=CC=C(C=C1)C#C[Si](C(C)C)(C(C)C)C(C)C Chemical compound C(C1=CC=CC=C1)NC1=CC=C(C=C1)C#C[Si](C(C)C)(C(C)C)C(C)C KTASQKTXUZWUGL-UHFFFAOYSA-N 0.000 description 2
• 201000004085 CLL/SLL Diseases 0.000 description 2
• 201000009030 Carcinoma Diseases 0.000 description 2
• 241000725101 Clea Species 0.000 description 2
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 241000588724 Escherichia coli Species 0.000 description 2
• GQHMGSCFLAONHH-UHFFFAOYSA-N FC=1C(=C(C#N)C=CC=1)C#C[Si](C)(C)C Chemical compound FC=1C(=C(C#N)C=CC=1)C#C[Si](C)(C)C GQHMGSCFLAONHH-UHFFFAOYSA-N 0.000 description 2
• 108010024636 Glutathione Proteins 0.000 description 2
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
• MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
• 102000003960 Ligases Human genes 0.000 description 2
• 108090000364 Ligases Proteins 0.000 description 2
• 206010025323 Lymphomas Diseases 0.000 description 2
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
• 208000025205 Mantle-Cell Lymphoma Diseases 0.000 description 2
• 241000699666 Mus <mouse, genus> Species 0.000 description 2
• 201000003793 Myelodysplastic syndrome Diseases 0.000 description 2
• AXOYDJMACIAVHX-UHFFFAOYSA-N N-ethyl-2-ethynyl-3-fluoroaniline Chemical compound C(C)NC1=C(C(=CC=C1)F)C#C AXOYDJMACIAVHX-UHFFFAOYSA-N 0.000 description 2
• WBRIZTMCPFEWOO-UHFFFAOYSA-N N-ethyl-4-ethynyl-3,5-difluoroaniline Chemical compound C(C)NC1=CC(=C(C(=C1)F)C#C)F WBRIZTMCPFEWOO-UHFFFAOYSA-N 0.000 description 2
• LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 2
• UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 2
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
• 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 description 2
• 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 2
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
• 208000015634 Rectal Neoplasms Diseases 0.000 description 2
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
• 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 2
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
• 108010076818 TEV protease Proteins 0.000 description 2
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
• 101150035006 UBA3 gene Proteins 0.000 description 2
• 102000044159 Ubiquitin Human genes 0.000 description 2
• 108090000848 Ubiquitin Proteins 0.000 description 2
• 238000001790 Welch's t-test Methods 0.000 description 2
• LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 2
• HEZCWNJAXVXKPR-XUTVFYLZSA-N [(3as,4r,6r,6ar)-4-amino-2,2-dimethyl-4,5,6,6a-tetrahydro-3ah-cyclopenta[d][1,3]dioxol-6-yl]methanol Chemical compound N[C@@H]1C[C@H](CO)[C@H]2OC(C)(C)O[C@H]21 HEZCWNJAXVXKPR-XUTVFYLZSA-N 0.000 description 2
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 125000003545 alkoxy group Chemical group 0.000 description 2
• 230000002421 anti-septic effect Effects 0.000 description 2
• 239000003963 antioxidant agent Substances 0.000 description 2
• 235000006708 antioxidants Nutrition 0.000 description 2
• 229940064004 antiseptic throat preparations Drugs 0.000 description 2
• 235000010323 ascorbic acid Nutrition 0.000 description 2
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 2
• 239000011324 bead Substances 0.000 description 2
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• 201000006491 bone marrow cancer Diseases 0.000 description 2
• 239000004327 boric acid Substances 0.000 description 2
• 210000000481 breast Anatomy 0.000 description 2
• 239000006285 cell suspension Substances 0.000 description 2
• 238000003570 cell viability assay Methods 0.000 description 2
• 230000001413 cellular effect Effects 0.000 description 2
• 229920002678 cellulose Polymers 0.000 description 2
• 239000001913 cellulose Substances 0.000 description 2
• 239000007795 chemical reaction product Substances 0.000 description 2
• 208000023738 chronic lymphocytic leukemia/small lymphocytic lymphoma Diseases 0.000 description 2
• 239000011248 coating agent Substances 0.000 description 2
• 239000003086 colorant Substances 0.000 description 2
• 229910052802 copper Inorganic materials 0.000 description 2
• 239000010949 copper Substances 0.000 description 2
• 230000008025 crystallization Effects 0.000 description 2
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
• 230000003247 decreasing effect Effects 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• 235000014113 dietary fatty acids Nutrition 0.000 description 2
• 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 2
• 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 2
• 239000007884 disintegrant Substances 0.000 description 2
• 238000001647 drug administration Methods 0.000 description 2
• 238000005516 engineering process Methods 0.000 description 2
• 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 2
• 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 2
• 239000000194 fatty acid Substances 0.000 description 2
• 229930195729 fatty acid Natural products 0.000 description 2
• 239000000835 fiber Substances 0.000 description 2
• 239000000706 filtrate Substances 0.000 description 2
• 235000019634 flavors Nutrition 0.000 description 2
• 235000003599 food sweetener Nutrition 0.000 description 2
• 235000019253 formic acid Nutrition 0.000 description 2
• 210000004211 gastric acid Anatomy 0.000 description 2
• 239000000499 gel Substances 0.000 description 2
• 201000009277 hairy cell leukemia Diseases 0.000 description 2
• 125000000623 heterocyclic group Chemical group 0.000 description 2
• 239000000833 heterodimer Substances 0.000 description 2
• GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
• 102000057318 human NAE Human genes 0.000 description 2
• 150000003840 hydrochlorides Chemical class 0.000 description 2
• 230000007062 hydrolysis Effects 0.000 description 2
• 238000006460 hydrolysis reaction Methods 0.000 description 2
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
• 229960003943 hypromellose Drugs 0.000 description 2
• 229910052740 iodine Inorganic materials 0.000 description 2
• 238000002955 isolation Methods 0.000 description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
• 125000005956 isoquinolyl group Chemical group 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 239000003446 ligand Substances 0.000 description 2
• 239000000314 lubricant Substances 0.000 description 2
• 208000003747 lymphoid leukemia Diseases 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 208000020968 mature T-cell and NK-cell non-Hodgkin lymphoma Diseases 0.000 description 2
• 239000002609 medium Substances 0.000 description 2
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 2
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 2
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 2
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 2
• HWZBVEPECDIDCA-UHFFFAOYSA-N n-benzyl-4-ethynylaniline Chemical compound C1=CC(C#C)=CC=C1NCC1=CC=CC=C1 HWZBVEPECDIDCA-UHFFFAOYSA-N 0.000 description 2
• 125000004957 naphthylene group Chemical group 0.000 description 2
• 230000017095 negative regulation of cell growth Effects 0.000 description 2
• 230000009826 neoplastic cell growth Effects 0.000 description 2
• 230000000269 nucleophilic effect Effects 0.000 description 2
• 210000000056 organ Anatomy 0.000 description 2
• 150000007530 organic bases Chemical class 0.000 description 2
• 125000005564 oxazolylene group Chemical group 0.000 description 2
• 230000003647 oxidation Effects 0.000 description 2
• 238000007254 oxidation reaction Methods 0.000 description 2
• 201000002528 pancreatic cancer Diseases 0.000 description 2
• 239000000546 pharmaceutical excipient Substances 0.000 description 2
• 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 2
• 230000004962 physiological condition Effects 0.000 description 2
• 230000036470 plasma concentration Effects 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
• 229920000053 polysorbate 80 Polymers 0.000 description 2
• 238000012746 preparative thin layer chromatography Methods 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• 239000000651 prodrug Substances 0.000 description 2
• 229940002612 prodrug Drugs 0.000 description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical class C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 2
• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 2
• 150000004944 pyrrolopyrimidines Chemical group 0.000 description 2
• 238000001953 recrystallisation Methods 0.000 description 2
• 206010038038 rectal cancer Diseases 0.000 description 2
• 201000001275 rectum cancer Diseases 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 238000012552 review Methods 0.000 description 2
• 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 2
• 239000012279 sodium borohydride Substances 0.000 description 2
• 229910000033 sodium borohydride Inorganic materials 0.000 description 2
• GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
• 239000012453 solvate Substances 0.000 description 2
• 238000000527 sonication Methods 0.000 description 2
• 206010062113 splenic marginal zone lymphoma Diseases 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• QAHVHSLSRLSVGS-UHFFFAOYSA-N sulfamoyl chloride Chemical compound NS(Cl)(=O)=O QAHVHSLSRLSVGS-UHFFFAOYSA-N 0.000 description 2
• 229910021653 sulphate ion Inorganic materials 0.000 description 2
• 239000006228 supernatant Substances 0.000 description 2
• 230000004083 survival effect Effects 0.000 description 2
• 239000000375 suspending agent Substances 0.000 description 2
• 239000003765 sweetening agent Substances 0.000 description 2
• WPCQASPMIALUEE-UHFFFAOYSA-N tert-butyl n-sulfamoylcarbamate Chemical compound CC(C)(C)OC(=O)NS(N)(=O)=O WPCQASPMIALUEE-UHFFFAOYSA-N 0.000 description 2
• CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 2
• 229940124597 therapeutic agent Drugs 0.000 description 2
• 125000005557 thiazolylene group Chemical group 0.000 description 2
• 125000005556 thienylene group Chemical group 0.000 description 2
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 2
• 125000005505 thiomorpholino group Chemical group 0.000 description 2
• BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 2
• 238000000825 ultraviolet detection Methods 0.000 description 2
• 239000003643 water by type Substances 0.000 description 2
• NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 1
• VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
• JZMJNHMUPFGYFK-UHFFFAOYSA-N (1-ethynylcyclopropyl)benzene Chemical compound C=1C=CC=CC=1C1(C#C)CC1 JZMJNHMUPFGYFK-UHFFFAOYSA-N 0.000 description 1
• XZINXOOZVCWXSP-PBXRRBTRSA-N (1s,2r,4r)-4-amino-2-(hydroxymethyl)cyclopentan-1-ol Chemical compound N[C@H]1C[C@H](O)[C@@H](CO)C1 XZINXOOZVCWXSP-PBXRRBTRSA-N 0.000 description 1
• GZAXBZYFKVKGLS-DJLDLDEBSA-N (2R,3S,5R)-2-(2-aminoethyl)-5-(4-amino-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)oxolan-3-ol Chemical compound NC=1C2=C(N=CN=1)N(C=C2I)[C@H]1C[C@@H]([C@H](O1)CCN)O GZAXBZYFKVKGLS-DJLDLDEBSA-N 0.000 description 1
• VIMLLKAYUJLXBE-RCCFBDPRSA-N (2R,3S,5R)-5-[4-amino-5-(1-benzylpyrazol-4-yl)pyrrolo[2,3-d]pyrimidin-7-yl]-2-(hydroxymethyl)oxolan-3-ol Chemical compound NC=1C2=C(N=CN=1)N(C=C2C=1C=NN(C=1)CC1=CC=CC=C1)[C@H]1C[C@@H]([C@H](O1)CO)O VIMLLKAYUJLXBE-RCCFBDPRSA-N 0.000 description 1
• BIWOSRSKDCZIFM-RXMQYKEDSA-N (3r)-piperidin-3-ol Chemical compound O[C@@H]1CCCNC1 BIWOSRSKDCZIFM-RXMQYKEDSA-N 0.000 description 1
• CDDGNGVFPQRJJM-BYPYZUCNSA-N (3s)-3-fluoropyrrolidine Chemical compound F[C@H]1CCNC1 CDDGNGVFPQRJJM-BYPYZUCNSA-N 0.000 description 1
• JHHZLHWJQPUNKB-BYPYZUCNSA-N (3s)-pyrrolidin-3-ol Chemical compound O[C@H]1CCNC1 JHHZLHWJQPUNKB-BYPYZUCNSA-N 0.000 description 1
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
• HEVMDQBCAHEHDY-UHFFFAOYSA-N (Dimethoxymethyl)benzene Chemical group COC(OC)C1=CC=CC=C1 HEVMDQBCAHEHDY-UHFFFAOYSA-N 0.000 description 1
• USVVENVKYJZFMW-ONEGZZNKSA-N (e)-carboxyiminocarbamic acid Chemical class OC(=O)\N=N\C(O)=O USVVENVKYJZFMW-ONEGZZNKSA-N 0.000 description 1
• MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
• 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 1
• RKOUFQLNMRAACI-UHFFFAOYSA-N 1,1,1-trifluoro-2-iodoethane Chemical compound FC(F)(F)CI RKOUFQLNMRAACI-UHFFFAOYSA-N 0.000 description 1
• SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical group COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 1
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
• LQIAZOCLNBBZQK-UHFFFAOYSA-N 1-(1,2-Diphosphanylethyl)pyrrolidin-2-one Chemical compound PCC(P)N1CCCC1=O LQIAZOCLNBBZQK-UHFFFAOYSA-N 0.000 description 1
• PSSOLQMYDTWFCH-UHFFFAOYSA-N 1-(chloromethyl)pyrazole;hydrochloride Chemical compound Cl.ClCN1C=CC=N1 PSSOLQMYDTWFCH-UHFFFAOYSA-N 0.000 description 1
• XMEAIJWQSPPMCQ-UHFFFAOYSA-N 1-(difluoromethoxy)-2-ethynylbenzene Chemical compound FC(F)OC1=CC=CC=C1C#C XMEAIJWQSPPMCQ-UHFFFAOYSA-N 0.000 description 1
• PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
• ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
• WQPDKRLNZPCLDW-WGQQHEPDSA-N 1-[2-[4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidin-5-yl]ethynyl]isoquinoline Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=NC=CC2=CC=CC=C12)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O WQPDKRLNZPCLDW-WGQQHEPDSA-N 0.000 description 1
• KXDPVPNXHFRQHM-WACONMJISA-N 1-[4-[2-[4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidin-5-yl]ethynyl]-3,5-difluorophenyl]pyrrolidine-3-carboxylic acid Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1F)N1CC(CC1)C(=O)O)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O KXDPVPNXHFRQHM-WACONMJISA-N 0.000 description 1
• REUXZHQDXRDRII-UHFFFAOYSA-N 1-bromo-2-ethylsulfanylbenzene Chemical compound CCSC1=CC=CC=C1Br REUXZHQDXRDRII-UHFFFAOYSA-N 0.000 description 1
• OJSFTIAXFDDUMI-UHFFFAOYSA-N 1-bromo-4-methoxy-2-methylsulfonylbenzene Chemical compound COC1=CC=C(Br)C(S(C)(=O)=O)=C1 OJSFTIAXFDDUMI-UHFFFAOYSA-N 0.000 description 1
• DGLHLIWXYSGYBI-UHFFFAOYSA-N 1-chloro-2-ethynylbenzene Chemical compound ClC1=CC=CC=C1C#C DGLHLIWXYSGYBI-UHFFFAOYSA-N 0.000 description 1
• SQSJADMOVKSAQY-UHFFFAOYSA-N 1-ethoxy-2-fluorobenzene Chemical compound CCOC1=CC=CC=C1F SQSJADMOVKSAQY-UHFFFAOYSA-N 0.000 description 1
• GMNOQQWCFQQIHO-UHFFFAOYSA-N 1-ethylsulfanyl-3-fluorobenzene Chemical compound CCSC1=CC=CC(F)=C1 GMNOQQWCFQQIHO-UHFFFAOYSA-N 0.000 description 1
• DMCAWSIZRCCGGK-UHFFFAOYSA-N 1-ethynyl-2,3-dihydro-1h-indene Chemical compound C1=CC=C2C(C#C)CCC2=C1 DMCAWSIZRCCGGK-UHFFFAOYSA-N 0.000 description 1
• QWFMOKRCLHCPSJ-UHFFFAOYSA-N 1-ethynyl-2-(trifluoromethoxy)benzene Chemical compound FC(F)(F)OC1=CC=CC=C1C#C QWFMOKRCLHCPSJ-UHFFFAOYSA-N 0.000 description 1
• YFPQIXUNBPQKQR-UHFFFAOYSA-N 1-ethynyl-2-fluorobenzene Chemical compound FC1=CC=CC=C1C#C YFPQIXUNBPQKQR-UHFFFAOYSA-N 0.000 description 1
• UFOVULIWACVAAC-UHFFFAOYSA-N 1-ethynyl-2-methoxybenzene Chemical compound COC1=CC=CC=C1C#C UFOVULIWACVAAC-UHFFFAOYSA-N 0.000 description 1
• MVXMSHPNQSBXFO-UHFFFAOYSA-N 1-ethynyl-2-methoxynaphthalene Chemical compound C1=CC=CC2=C(C#C)C(OC)=CC=C21 MVXMSHPNQSBXFO-UHFFFAOYSA-N 0.000 description 1
• MZJBVUUULYVFQH-UHFFFAOYSA-N 1-ethynyl-4-(phenoxymethyl)benzene Chemical compound C1=CC(C#C)=CC=C1COC1=CC=CC=C1 MZJBVUUULYVFQH-UHFFFAOYSA-N 0.000 description 1
• YJUQVJUCIZWTSQ-UHFFFAOYSA-N 1-ethynyl-4-methoxy-2-methylsulfonylbenzene Chemical compound C(#C)C1=C(C=C(C=C1)OC)S(=O)(=O)C YJUQVJUCIZWTSQ-UHFFFAOYSA-N 0.000 description 1
• XQHAOXRZNLCKJO-UHFFFAOYSA-N 1-ethynyl-4-phenylmethoxybenzene Chemical compound C1=CC(C#C)=CC=C1OCC1=CC=CC=C1 XQHAOXRZNLCKJO-UHFFFAOYSA-N 0.000 description 1
• PTRWXSTUHSTRHM-UHFFFAOYSA-N 1-ethynylisoquinoline Chemical compound C1=CC=C2C(C#C)=NC=CC2=C1 PTRWXSTUHSTRHM-UHFFFAOYSA-N 0.000 description 1
• XWAKVQSVEHWEJO-UHFFFAOYSA-N 1-fluoro-2-prop-2-ynylbenzene Chemical compound FC1=CC=CC=C1CC#C XWAKVQSVEHWEJO-UHFFFAOYSA-N 0.000 description 1
• AXWBMIJJRDKELE-UHFFFAOYSA-N 1-iodo-2-methylsulfanyl-4-phenylmethoxybenzene Chemical compound C(C1=CC=CC=C1)OC=1C=CC(=C(C=1)SC)I AXWBMIJJRDKELE-UHFFFAOYSA-N 0.000 description 1
• 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
• 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 1
• HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 1
• SPSPIUSUWPLVKD-UHFFFAOYSA-N 2,3-dibutyl-6-methylphenol Chemical compound CCCCC1=CC=C(C)C(O)=C1CCCC SPSPIUSUWPLVKD-UHFFFAOYSA-N 0.000 description 1
• CYOGOUIOPPJJKK-UHFFFAOYSA-N 2,3-dihydro-1-benzothiophene-7-carbaldehyde Chemical compound O=CC1=CC=CC2=C1SCC2 CYOGOUIOPPJJKK-UHFFFAOYSA-N 0.000 description 1
• KPJIEPBITZLHPQ-UHFFFAOYSA-N 2,4,6-trifluorobenzaldehyde Chemical compound FC1=CC(F)=C(C=O)C(F)=C1 KPJIEPBITZLHPQ-UHFFFAOYSA-N 0.000 description 1
• WCGPCBACLBHDCI-UHFFFAOYSA-N 2,4-difluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C(F)=C1 WCGPCBACLBHDCI-UHFFFAOYSA-N 0.000 description 1
• OCEBQLYVUCEZJC-UHFFFAOYSA-N 2,4-difluoropyridine-3-carbaldehyde Chemical compound FC1=CC=NC(F)=C1C=O OCEBQLYVUCEZJC-UHFFFAOYSA-N 0.000 description 1
• BGSYNRGGTPGLHR-MRVPVSSYSA-N 2,6-difluoro-4-[(3R)-3-hydroxypyrrolidin-1-yl]benzaldehyde Chemical compound FC1=C(C=O)C(=CC(=C1)N1C[C@@H](CC1)O)F BGSYNRGGTPGLHR-MRVPVSSYSA-N 0.000 description 1
• SOWRUJSGHKNOKN-UHFFFAOYSA-N 2,6-difluorobenzaldehyde Chemical compound FC1=CC=CC(F)=C1C=O SOWRUJSGHKNOKN-UHFFFAOYSA-N 0.000 description 1
• KLIDCXVFHGNTTM-UHFFFAOYSA-N 2,6-dimethoxyphenol Chemical group COC1=CC=CC(OC)=C1O KLIDCXVFHGNTTM-UHFFFAOYSA-N 0.000 description 1
• CTZZEBNNWDVUFO-UHFFFAOYSA-N 2-(5-ethynylthiophen-2-yl)pyridine Chemical compound S1C(C#C)=CC=C1C1=CC=CC=N1 CTZZEBNNWDVUFO-UHFFFAOYSA-N 0.000 description 1
• PRGPKCHJKNCEOZ-UHFFFAOYSA-N 2-(chloromethyl)triazole Chemical compound ClCN1N=CC=N1 PRGPKCHJKNCEOZ-UHFFFAOYSA-N 0.000 description 1
• JATUBLZMVPJFGG-BGIGGGFGSA-N 2-[2-[4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidin-5-yl]ethynyl]-3-fluorobenzenesulfonamide Chemical compound Nc1ncnc2n(cc(C#Cc3c(F)cccc3S(N)(=O)=O)c12)[C@@H]1O[C@H](CNS(N)(=O)=O)[C@@H](O)[C@H]1O JATUBLZMVPJFGG-BGIGGGFGSA-N 0.000 description 1
• AJWLISNRGQWCFF-BGIGGGFGSA-N 2-[2-[4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidin-5-yl]ethynyl]benzenesulfonamide Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1)S(=O)(=O)N)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O AJWLISNRGQWCFF-BGIGGGFGSA-N 0.000 description 1
• QHUDDDWGZQPDIC-UHFFFAOYSA-N 2-bromopyrimidin-5-ol Chemical compound OC1=CN=C(Br)N=C1 QHUDDDWGZQPDIC-UHFFFAOYSA-N 0.000 description 1
• OACPOWYLLGHGCR-UHFFFAOYSA-N 2-chloro-6-fluorobenzaldehyde Chemical compound FC1=CC=CC(Cl)=C1C=O OACPOWYLLGHGCR-UHFFFAOYSA-N 0.000 description 1
• UDZGHTHYVWDFFY-UHFFFAOYSA-N 2-chlorobutan-2-ol Chemical compound CCC(C)(O)Cl UDZGHTHYVWDFFY-UHFFFAOYSA-N 0.000 description 1
• YAOCKWIPUMIUEO-UHFFFAOYSA-N 2-ethylsulfonyl-6-fluoro-4-pyrrolidin-1-ylbenzaldehyde Chemical compound C(C)S(=O)(=O)C1=C(C=O)C(=CC(=C1)N1CCCC1)F YAOCKWIPUMIUEO-UHFFFAOYSA-N 0.000 description 1
• DIYQFCBUYPOLQL-UHFFFAOYSA-N 2-ethynyl-3-fluorobenzenesulfonamide Chemical compound C(#C)C1=C(C=CC=C1F)S(=O)(=O)N DIYQFCBUYPOLQL-UHFFFAOYSA-N 0.000 description 1
• JOLDOSMKSCCFCJ-UHFFFAOYSA-N 2-ethynyl-3-fluorobenzenethiol Chemical compound C(#C)C1=C(C=CC=C1F)S JOLDOSMKSCCFCJ-UHFFFAOYSA-N 0.000 description 1
• LZSDQLUEGYXDCW-UHFFFAOYSA-N 2-ethynylbenzonitrile Chemical compound C#CC1=CC=CC=C1C#N LZSDQLUEGYXDCW-UHFFFAOYSA-N 0.000 description 1
• NHUBNHMFXQNNMV-UHFFFAOYSA-N 2-ethynylpyridine Chemical compound C#CC1=CC=CC=N1 NHUBNHMFXQNNMV-UHFFFAOYSA-N 0.000 description 1
• YHFJYKGTZBMBQQ-UHFFFAOYSA-N 2-fluoro-6-methylsulfanylbenzaldehyde Chemical compound CSC1=CC=CC(F)=C1C=O YHFJYKGTZBMBQQ-UHFFFAOYSA-N 0.000 description 1
• DZJPDDVDKXHRLF-UHFFFAOYSA-N 2-hydroxy-6-methoxybenzaldehyde Chemical compound COC1=CC=CC(O)=C1C=O DZJPDDVDKXHRLF-UHFFFAOYSA-N 0.000 description 1
• JKHHRSIUFVAEOY-UHFFFAOYSA-N 2-iodobenzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1I JKHHRSIUFVAEOY-UHFFFAOYSA-N 0.000 description 1
• HZLNIOUBXRIFML-UHFFFAOYSA-N 2-methoxy-4-phenylmethoxybenzaldehyde Chemical compound C1=C(C=O)C(OC)=CC(OCC=2C=CC=CC=2)=C1 HZLNIOUBXRIFML-UHFFFAOYSA-N 0.000 description 1
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
• QTWJRLJHJPIABL-UHFFFAOYSA-N 2-methylphenol;3-methylphenol;4-methylphenol Chemical compound CC1=CC=C(O)C=C1.CC1=CC=CC(O)=C1.CC1=CC=CC=C1O QTWJRLJHJPIABL-UHFFFAOYSA-N 0.000 description 1
• OGAUXOMRNVADMD-UHFFFAOYSA-N 2-methylsulfanyl-4-piperidin-1-ylbenzaldehyde Chemical compound CSC1=C(C=O)C=CC(=C1)N1CCCCC1 OGAUXOMRNVADMD-UHFFFAOYSA-N 0.000 description 1
• 125000006185 3,4-dimethyl benzyl group Chemical group [H]C1=C(C([H])=C(C(=C1[H])C([H])([H])[H])C([H])([H])[H])C([H])([H])* 0.000 description 1
• GOBXWYWTZCKDBF-UHFFFAOYSA-N 3,5-difluoro-4-formylbenzonitrile Chemical compound FC1=CC(C#N)=CC(F)=C1C=O GOBXWYWTZCKDBF-UHFFFAOYSA-N 0.000 description 1
• HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
• WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
• AVQOYOGHDDCJKW-PFPFAPGLSA-N 3-[4-[2-[4-amino-7-[(1R,2S,3R,4R)-2,3-dihydroxy-4-[(sulfamoylamino)methyl]cyclopentyl]pyrrolo[2,3-d]pyrimidin-5-yl]ethynyl]-3-ethoxy-5-fluorophenyl]-8-oxa-3-azabicyclo[3.2.1]octane Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1F)N1CC2CCC(C1)O2)OCC)[C@H]1[C@@H]([C@@H]([C@H](C1)CNS(N)(=O)=O)O)O AVQOYOGHDDCJKW-PFPFAPGLSA-N 0.000 description 1
• REBICAKZCVGRBK-TXJANDSUSA-N 3-[[4-[2-[4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidin-5-yl]ethynyl]phenoxy]methyl]benzamide Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=CC=C(OCC=2C=C(C(=O)N)C=CC=2)C=C1)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O REBICAKZCVGRBK-TXJANDSUSA-N 0.000 description 1
• HWMVCSBQJWRQNF-UHFFFAOYSA-N 3-ethynyl-4-fluoroaniline Chemical compound NC1=CC=C(F)C(C#C)=C1 HWMVCSBQJWRQNF-UHFFFAOYSA-N 0.000 description 1
• CTRKEMNNTVYILZ-UHFFFAOYSA-N 3-ethynyl-n-propan-2-ylaniline Chemical compound CC(C)NC1=CC=CC(C#C)=C1 CTRKEMNNTVYILZ-UHFFFAOYSA-N 0.000 description 1
• GPKAQFJJYPQAHG-UHFFFAOYSA-N 3-fluoro-2-iodobenzamide Chemical compound NC(=O)C1=CC=CC(F)=C1I GPKAQFJJYPQAHG-UHFFFAOYSA-N 0.000 description 1
• DYUUGFOXEVSQLK-UHFFFAOYSA-N 3-fluoro-2-iodobenzenesulfonamide Chemical compound FC=1C(=C(C=CC=1)S(=O)(=O)N)I DYUUGFOXEVSQLK-UHFFFAOYSA-N 0.000 description 1
• LOHHYNZRGUOISS-UHFFFAOYSA-N 3-fluoro-2-iodobenzonitrile Chemical compound FC1=CC=CC(C#N)=C1I LOHHYNZRGUOISS-UHFFFAOYSA-N 0.000 description 1
• ZDGZTSMMMPDJLS-UHFFFAOYSA-N 3-fluoro-2-iodopyridine Chemical compound FC1=CC=CN=C1I ZDGZTSMMMPDJLS-UHFFFAOYSA-N 0.000 description 1
• UQXMVPSXSNPVKK-UHFFFAOYSA-N 3-fluoro-5-methoxypyridine-4-carbaldehyde Chemical compound COC1=CN=CC(F)=C1C=O UQXMVPSXSNPVKK-UHFFFAOYSA-N 0.000 description 1
• MNILDQSRDHCFJG-UHFFFAOYSA-N 3-oxa-8-azabicyclo[3.2.1]octane Chemical compound C1OCC2CCC1N2 MNILDQSRDHCFJG-UHFFFAOYSA-N 0.000 description 1
• TVOJIBGZFYMWDT-UHFFFAOYSA-N 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1h-pyrazole Chemical compound O1C(C)(C)C(C)(C)OB1C1=CNN=C1 TVOJIBGZFYMWDT-UHFFFAOYSA-N 0.000 description 1
• VFKHNJUFZOQFBX-UHFFFAOYSA-N 4-(4-ethynyl-3,5-difluorophenyl)-1,4-thiazinane 1,1-dioxide Chemical compound C(#C)C1=C(C=C(C=C1F)N1CCS(CC1)(=O)=O)F VFKHNJUFZOQFBX-UHFFFAOYSA-N 0.000 description 1
• UBQRAAXAHIKWRI-UHFFFAOYSA-N 4-(chloromethyl)-1,2-dimethylbenzene Chemical compound CC1=CC=C(CCl)C=C1C UBQRAAXAHIKWRI-UHFFFAOYSA-N 0.000 description 1
• GKYUQKOOOAYULN-ZDXOVATRSA-N 4-[4-[2-[4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidin-5-yl]ethynyl]-3,5-difluorophenyl]morpholine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1F)N1CCOCC1)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O GKYUQKOOOAYULN-ZDXOVATRSA-N 0.000 description 1
• NGSRXPAJUVEWLQ-ZDXOVATRSA-N 4-[4-[2-[4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidin-5-yl]ethynyl]-3,5-difluorophenyl]thiomorpholine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1F)N1CCSCC1)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O NGSRXPAJUVEWLQ-ZDXOVATRSA-N 0.000 description 1
• HQJQVWINQDACLV-VGKBRBPRSA-N 4-[4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidin-5-yl]-2-(2-methoxyphenyl)-1,3-thiazole Chemical compound NC=1C2=C(N=CN=1)N(C=C2C=1N=C(SC=1)C1=C(C=CC=C1)OC)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O HQJQVWINQDACLV-VGKBRBPRSA-N 0.000 description 1
• INIYTVKQXAECHX-KHTYJDQRSA-N 4-[4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidin-5-yl]-2-phenyl-1,3-oxazole Chemical compound NC=1C2=C(N=CN=1)N(C=C2C=1N=C(OC=1)C1=CC=CC=C1)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O INIYTVKQXAECHX-KHTYJDQRSA-N 0.000 description 1
• TVJUPVDQXHPNBO-GVDBMIGSSA-N 4-[4-amino-7-[(2R,4S,5R)-4-hydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidin-5-yl]-2-(2-methylphenyl)-1,3-thiazole Chemical compound NC=1C2=C(N=CN=1)N(C=C2C=1N=C(SC=1)C1=C(C=CC=C1)C)[C@@H]1O[C@@H]([C@H](C1)O)CNS(N)(=O)=O TVJUPVDQXHPNBO-GVDBMIGSSA-N 0.000 description 1
• YGZNDVDCVWAGAA-XWXWGSFUSA-N 4-amino-5-[2-(2,4-difluoropyridin-3-yl)ethynyl]-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC=1C(=NC=CC=1F)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O YGZNDVDCVWAGAA-XWXWGSFUSA-N 0.000 description 1
• FNCONUSZJUUDAV-NVQRDWNXSA-N 4-amino-5-[2-(2,6-difluoro-4-hydroxyphenyl)ethynyl]-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1F)O)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O FNCONUSZJUUDAV-NVQRDWNXSA-N 0.000 description 1
• RFLNJGQGVVIGEE-ICYYRSKXSA-N 4-amino-5-[2-(2,6-difluoro-4-piperidin-1-ylphenyl)ethynyl]-7-[(1R,2S,3R,4R)-2,3-dihydroxy-4-[(sulfamoylamino)methyl]cyclopentyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1F)N1CCCCC1)F)[C@H]1[C@@H]([C@@H]([C@H](C1)CNS(N)(=O)=O)O)O RFLNJGQGVVIGEE-ICYYRSKXSA-N 0.000 description 1
• LYHZGQNSCGNUPO-NXHRZFHOSA-N 4-amino-5-[2-(2,6-difluorophenyl)ethynyl]-7-[(1R,4R,5S)-4,5-dihydroxy-3-[(sulfamoylamino)methyl]cyclopent-2-en-1-yl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1F)F)[C@@H]1C=C([C@H]([C@H]1O)O)CNS(N)(=O)=O LYHZGQNSCGNUPO-NXHRZFHOSA-N 0.000 description 1
• TZDIFHOXXVBVGF-ARFHVFGLSA-N 4-amino-5-[2-(2,6-difluorophenyl)ethynyl]-7-[(2R,4S,5R)-4-hydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1F)F)[C@@H]1O[C@@H]([C@H](C1)O)CNS(N)(=O)=O TZDIFHOXXVBVGF-ARFHVFGLSA-N 0.000 description 1
• NSHUUDHSKRWOJI-NVQRDWNXSA-N 4-amino-5-[2-(2-chloro-6-fluorophenyl)ethynyl]-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1F)Cl)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O NSHUUDHSKRWOJI-NVQRDWNXSA-N 0.000 description 1
• FWQNSQZZWIZXPS-NVQRDWNXSA-N 4-amino-5-[2-(2-chlorophenyl)ethynyl]-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1)Cl)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O FWQNSQZZWIZXPS-NVQRDWNXSA-N 0.000 description 1
• DNTXKSXDJNHRAU-WVSUBDOOSA-N 4-amino-5-[2-(2-cyano-6-fluorophenyl)ethynyl]-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1F)C#N)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O DNTXKSXDJNHRAU-WVSUBDOOSA-N 0.000 description 1
• MUUQIQJALGNYAG-WVSUBDOOSA-N 4-amino-5-[2-(2-cyanophenyl)ethynyl]-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1)C#N)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O MUUQIQJALGNYAG-WVSUBDOOSA-N 0.000 description 1
• STIWSBZHMZCXNT-NVQRDWNXSA-N 4-amino-5-[2-(4-amino-2-fluorophenyl)ethynyl]-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1)N)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O STIWSBZHMZCXNT-NVQRDWNXSA-N 0.000 description 1
• UBLJAFWHKSSTMS-WVSUBDOOSA-N 4-amino-5-[2-(4-cyano-2,6-difluorophenyl)ethynyl]-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1F)C#N)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O UBLJAFWHKSSTMS-WVSUBDOOSA-N 0.000 description 1
• RGFIFORKJXVBBO-NVQRDWNXSA-N 4-amino-5-[2-(5-amino-2-fluorophenyl)ethynyl]-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC(=C1)N)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O RGFIFORKJXVBBO-NVQRDWNXSA-N 0.000 description 1
• OHVFRMLIVJAGBO-WGQQHEPDSA-N 4-amino-5-[2-[2,6-difluoro-4-(3-hydroxyazetidin-1-yl)phenyl]ethynyl]-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1F)N1CC(C1)O)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O OHVFRMLIVJAGBO-WGQQHEPDSA-N 0.000 description 1
• OOMQVGDBUICTSY-WGQQHEPDSA-N 4-amino-5-[2-[2,6-difluoro-4-(triazol-2-ylmethoxy)phenyl]ethynyl]-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1F)OCN1N=CC=N1)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O OOMQVGDBUICTSY-WGQQHEPDSA-N 0.000 description 1
• PRNCVCLXPJGNLF-POLKQERGSA-N 4-amino-5-[2-[2,6-difluoro-4-[(3R)-3-fluoropyrrolidin-1-yl]phenyl]ethynyl]-7-[(1R,2S,3R,4R)-2,3-dihydroxy-4-[(sulfamoylamino)methyl]cyclopentyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1F)N1C[C@@H](CC1)F)F)[C@H]1[C@@H]([C@@H]([C@H](C1)CNS(N)(=O)=O)O)O PRNCVCLXPJGNLF-POLKQERGSA-N 0.000 description 1
• HVADRGHAXPJXOY-QNQXRBRUSA-N 4-amino-5-[2-[2,6-difluoro-4-[(3R)-3-hydroxypiperidin-1-yl]phenyl]ethynyl]-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1F)N1C[C@@H](CCC1)O)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O HVADRGHAXPJXOY-QNQXRBRUSA-N 0.000 description 1
• STXGHJIKQABYFG-OVFFQXIUSA-N 4-amino-5-[2-[2,6-difluoro-4-[(3R)-3-hydroxypyrrolidin-1-yl]phenyl]ethynyl]-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1F)N1C[C@@H](CC1)O)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O STXGHJIKQABYFG-OVFFQXIUSA-N 0.000 description 1
• PRNCVCLXPJGNLF-CHNLTIPISA-N 4-amino-5-[2-[2,6-difluoro-4-[(3S)-3-fluoropyrrolidin-1-yl]phenyl]ethynyl]-7-[(1R,2S,3R,4R)-2,3-dihydroxy-4-[(sulfamoylamino)methyl]cyclopentyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1F)N1C[C@H](CC1)F)F)[C@H]1[C@@H]([C@@H]([C@H](C1)CNS(N)(=O)=O)O)O PRNCVCLXPJGNLF-CHNLTIPISA-N 0.000 description 1
• ZRIPIAROEXJLES-JUEFBOCKSA-N 4-amino-5-[2-[2,6-difluoro-4-[(3S)-3-hydroxypyrrolidin-1-yl]phenyl]ethynyl]-7-[(1R,2S,3R,4R)-2,3-dihydroxy-4-[(sulfamoylamino)methyl]cyclopentyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1F)N1C[C@H](CC1)O)F)[C@H]1[C@@H]([C@@H]([C@H](C1)CNS(N)(=O)=O)O)O ZRIPIAROEXJLES-JUEFBOCKSA-N 0.000 description 1
• AHIFOGNWIWXTET-NDKINLCJSA-N 4-amino-5-[2-[4-(azetidin-1-yl)-2,6-difluorophenyl]ethynyl]-7-[(1R,2S,3R,4R)-2,3-dihydroxy-4-[(sulfamoylamino)methyl]cyclopentyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1F)N1CCC1)F)[C@H]1[C@@H]([C@@H]([C@H](C1)CNS(N)(=O)=O)O)O AHIFOGNWIWXTET-NDKINLCJSA-N 0.000 description 1
• BFGHTMHTEIPSPG-WGQQHEPDSA-N 4-amino-5-[2-[4-(azetidin-1-yl)-2,6-difluorophenyl]ethynyl]-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1F)N1CCC1)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O BFGHTMHTEIPSPG-WGQQHEPDSA-N 0.000 description 1
• APQVMZQYMFYGRZ-HUBRGWSESA-N 4-amino-5-[2-[4-(benzylamino)phenyl]ethynyl]-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=CC=C(C=C1)NCC1=CC=CC=C1)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O APQVMZQYMFYGRZ-HUBRGWSESA-N 0.000 description 1
• KDKAVBRRHIYCMW-WVSUBDOOSA-N 4-amino-5-[3-(2,6-difluorophenyl)prop-1-ynyl]-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CCC1=C(C=CC=C1F)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O KDKAVBRRHIYCMW-WVSUBDOOSA-N 0.000 description 1
• KXUMXYLMLCJBEZ-IYERYRBDSA-N 4-amino-7-[(1R,2S,3R,4R)-2,3-dihydroxy-4-[(sulfamoylamino)methyl]cyclopentyl]-5-(2-naphthalen-1-ylethynyl)pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=CC=CC2=CC=CC=C12)[C@H]1[C@@H]([C@@H]([C@H](C1)CNS(N)(=O)=O)O)O KXUMXYLMLCJBEZ-IYERYRBDSA-N 0.000 description 1
• FHDXIAHSUYVWKI-RWQQGDIJSA-N 4-amino-7-[(1R,2S,3R,4R)-2,3-dihydroxy-4-[(sulfamoylamino)methyl]cyclopentyl]-5-[2-(1,1-dioxo-2,3-dihydro-1-benzothiophen-7-yl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=CC=CC=2CCS(C=21)(=O)=O)[C@H]1[C@@H]([C@@H]([C@H](C1)CNS(N)(=O)=O)O)O FHDXIAHSUYVWKI-RWQQGDIJSA-N 0.000 description 1
• LIICLFTZAOLLBA-LFGUQSLTSA-N 4-amino-7-[(1R,2S,3R,4R)-2,3-dihydroxy-4-[(sulfamoylamino)methyl]cyclopentyl]-5-[2-(1,1-dioxo-3,4-dihydro-2H-thiochromen-8-yl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC=1C=CC=C2CCCS(C=12)(=O)=O)[C@H]1[C@@H]([C@@H]([C@H](C1)CNS(N)(=O)=O)O)O LIICLFTZAOLLBA-LFGUQSLTSA-N 0.000 description 1
• QGBBIVKHRJHZCW-ODQPLOLNSA-N 4-amino-7-[(1R,2S,3R,4R)-2,3-dihydroxy-4-[(sulfamoylamino)methyl]cyclopentyl]-5-[2-(2-ethoxy-6-fluoro-4-piperidin-1-ylphenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1F)N1CCCCC1)OCC)[C@H]1[C@@H]([C@@H]([C@H](C1)CNS(N)(=O)=O)O)O QGBBIVKHRJHZCW-ODQPLOLNSA-N 0.000 description 1
• KTVGWSPGGHSAIA-JMLZYGAQSA-N 4-amino-7-[(1R,2S,3R,4R)-2,3-dihydroxy-4-[(sulfamoylamino)methyl]cyclopentyl]-5-[2-(2-ethoxy-6-fluorophenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1F)OCC)[C@H]1[C@@H]([C@@H]([C@H](C1)CNS(N)(=O)=O)O)O KTVGWSPGGHSAIA-JMLZYGAQSA-N 0.000 description 1
• XIVWAMAACLAYJR-XQJRBRMLSA-N 4-amino-7-[(1R,2S,3R,4R)-2,3-dihydroxy-4-[(sulfamoylamino)methyl]cyclopentyl]-5-[2-(2-ethoxy-6-methoxyphenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1OC)OCC)[C@H]1[C@@H]([C@@H]([C@H](C1)CNS(N)(=O)=O)O)O XIVWAMAACLAYJR-XQJRBRMLSA-N 0.000 description 1
• RURLZQAQSDDHAB-JMLZYGAQSA-N 4-amino-7-[(1R,2S,3R,4R)-2,3-dihydroxy-4-[(sulfamoylamino)methyl]cyclopentyl]-5-[2-(2-ethylsulfanyl-6-fluorophenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1F)SCC)[C@H]1[C@@H]([C@@H]([C@H](C1)CNS(N)(=O)=O)O)O RURLZQAQSDDHAB-JMLZYGAQSA-N 0.000 description 1
• KKOUHJSEBBTPEJ-RWJCITIMSA-N 4-amino-7-[(1R,2S,3R,4R)-2,3-dihydroxy-4-[(sulfamoylamino)methyl]cyclopentyl]-5-[2-(2-ethylsulfonyl-6-fluoro-4-pyrrolidin-1-ylphenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1F)N1CCCC1)S(=O)(=O)CC)[C@H]1[C@@H]([C@@H]([C@H](C1)CNS(N)(=O)=O)O)O KKOUHJSEBBTPEJ-RWJCITIMSA-N 0.000 description 1
• CVYDWKYOJWIZRN-JMLZYGAQSA-N 4-amino-7-[(1R,2S,3R,4R)-2,3-dihydroxy-4-[(sulfamoylamino)methyl]cyclopentyl]-5-[2-(2-ethylsulfonyl-6-fluorophenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1F)S(=O)(=O)CC)[C@H]1[C@@H]([C@@H]([C@H](C1)CNS(N)(=O)=O)O)O CVYDWKYOJWIZRN-JMLZYGAQSA-N 0.000 description 1
• OVMCSLCZYMIVPN-SNTIZLKRSA-N 4-amino-7-[(1R,2S,3R,4R)-2,3-dihydroxy-4-[(sulfamoylamino)methyl]cyclopentyl]-5-[2-(2-fluoro-6-methoxyphenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1OC)F)[C@H]1[C@@H]([C@@H]([C@H](C1)CNS(N)(=O)=O)O)O OVMCSLCZYMIVPN-SNTIZLKRSA-N 0.000 description 1
• ZYCXPAXWMXDIKW-ILEGPTGMSA-N 4-amino-7-[(1R,2S,3R,4R)-2,3-dihydroxy-4-[(sulfamoylamino)methyl]cyclopentyl]-5-[2-(2-methylsulfanyl-4-piperidin-1-ylphenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1)N1CCCCC1)SC)[C@H]1[C@@H]([C@@H]([C@H](C1)CNS(N)(=O)=O)O)O ZYCXPAXWMXDIKW-ILEGPTGMSA-N 0.000 description 1
• XSQKYFVSOITAAB-XPLBRSQRSA-N 4-amino-7-[(1R,2S,3R,4R)-2,3-dihydroxy-4-[(sulfamoylamino)methyl]cyclopentyl]-5-[2-(2-methylsulfonyl-4-phenylmethoxyphenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1)OCC1=CC=CC=C1)S(=O)(=O)C)[C@H]1[C@@H]([C@@H]([C@H](C1)CNS(N)(=O)=O)O)O XSQKYFVSOITAAB-XPLBRSQRSA-N 0.000 description 1
• GSJQLSNJCIFAOR-FCNFAXOHSA-N 4-amino-7-[(1R,2S,3R,4R)-2,3-dihydroxy-4-[(sulfamoylamino)methyl]cyclopentyl]-5-[2-(4-methoxy-2-methylsulfonylphenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1)OC)S(=O)(=O)C)[C@H]1[C@@H]([C@@H]([C@H](C1)CNS(N)(=O)=O)O)O GSJQLSNJCIFAOR-FCNFAXOHSA-N 0.000 description 1
• ORKUOAAGCVVVGJ-AHRSYUTCSA-N 4-amino-7-[(1R,4R,5S)-4,5-dihydroxy-3-[(sulfamoylamino)methyl]cyclopent-2-en-1-yl]-5-[2-(2-ethoxy-6-fluorophenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1F)OCC)[C@@H]1C=C([C@H]([C@H]1O)O)CNS(N)(=O)=O ORKUOAAGCVVVGJ-AHRSYUTCSA-N 0.000 description 1
• YUQVOBKVBDPDAC-ZDXOVATRSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-(2-naphthalen-1-ylethynyl)pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=CC=CC2=CC=CC=C12)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O YUQVOBKVBDPDAC-ZDXOVATRSA-N 0.000 description 1
• LCPMCJDWHGBFKZ-SCFUHWHPSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-(2-pyridin-2-ylethynyl)pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=NC=CC=C1)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O LCPMCJDWHGBFKZ-SCFUHWHPSA-N 0.000 description 1
• UATQWEZQVGIWIN-WVSUBDOOSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-(3-phenylprop-1-ynyl)pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CCC1=CC=CC=C1)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O UATQWEZQVGIWIN-WVSUBDOOSA-N 0.000 description 1
• MPZKJXXVVBRVGK-UVLLPENVSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(1,1-dioxo-3,4-dihydro-2H-thiochromen-8-yl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC=1C=CC=C2CCCS(C=12)(=O)=O)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O MPZKJXXVVBRVGK-UVLLPENVSA-N 0.000 description 1
• BWCXZWWIGPFCNK-QTQZEZTPSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(1-phenylcyclopropyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1(CC1)C1=CC=CC=C1)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O BWCXZWWIGPFCNK-QTQZEZTPSA-N 0.000 description 1
• ANDSWLJQJWIYDW-NVQRDWNXSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(1H-pyrazolo[4,3-b]pyridin-5-yl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=CC=C2C(=N1)C=NN2)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O ANDSWLJQJWIYDW-NVQRDWNXSA-N 0.000 description 1
• GXOXAGLTJYVCTA-KHTYJDQRSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(2,4-dimethoxypyridin-3-yl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC=1C(=NC=CC=1OC)OC)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O GXOXAGLTJYVCTA-KHTYJDQRSA-N 0.000 description 1
• RNMXZMWCBVMKKL-QTQZEZTPSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(2,6-dimethoxyphenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1OC)OC)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O RNMXZMWCBVMKKL-QTQZEZTPSA-N 0.000 description 1
• MBEFSHJJYRSJKF-QTQZEZTPSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(2-ethoxy-4,6-difluorophenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1F)F)OCC)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O MBEFSHJJYRSJKF-QTQZEZTPSA-N 0.000 description 1
• TZTRUHFXPVXWRD-QTQZEZTPSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(2-ethoxy-6-fluorophenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1F)OCC)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O TZTRUHFXPVXWRD-QTQZEZTPSA-N 0.000 description 1
• CDCFJYCKNAWPTL-WVAMHNCPSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(2-ethoxy-6-fluorophenyl)ethynyl]pyrrolo[2,3-d]pyrimidine hydrochloride Chemical compound Cl.CCOc1cccc(F)c1C#Cc1cn([C@@H]2O[C@H](CNS(N)(=O)=O)[C@@H](O)[C@H]2O)c2ncnc(N)c12 CDCFJYCKNAWPTL-WVAMHNCPSA-N 0.000 description 1
• MERSQKPCYCVVAJ-WGQQHEPDSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(2-ethoxy-6-methoxyphenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1OC)OCC)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O MERSQKPCYCVVAJ-WGQQHEPDSA-N 0.000 description 1
• DYHJPWKYSQPZRM-HAXDFEGKSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(2-ethylsulfanyl-6-fluorophenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1F)SCC)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O DYHJPWKYSQPZRM-HAXDFEGKSA-N 0.000 description 1
• ZEOYNNFFCNWJSK-HAXDFEGKSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(2-ethylsulfanylphenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1)SCC)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O ZEOYNNFFCNWJSK-HAXDFEGKSA-N 0.000 description 1
• RBPDFRIQWJZXET-PXOHRUDZSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(2-ethylsulfonyl-6-fluoro-4-pyrrolidin-1-ylphenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1F)N1CCCC1)S(=O)(=O)CC)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O RBPDFRIQWJZXET-PXOHRUDZSA-N 0.000 description 1
• BBUWGOZCYGHSHN-HAXDFEGKSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(2-ethylsulfonyl-6-fluorophenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1F)S(=O)(=O)CC)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O BBUWGOZCYGHSHN-HAXDFEGKSA-N 0.000 description 1
• SZDILWNLOFFTIW-HUBRGWSESA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(2-fluoro-4-phenylmethoxyphenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1)OCC1=CC=CC=C1)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O SZDILWNLOFFTIW-HUBRGWSESA-N 0.000 description 1
• PLRYZUJMRVKDLN-WVSUBDOOSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(2-fluoro-6-methoxyphenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1OC)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O PLRYZUJMRVKDLN-WVSUBDOOSA-N 0.000 description 1
• SFOGVSNJYUAISW-AEVYOOLXSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(2-fluoro-6-methylsulfanylphenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1SC)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O SFOGVSNJYUAISW-AEVYOOLXSA-N 0.000 description 1
• BZJKRVBQUMLZIP-WGQQHEPDSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(2-fluoro-6-propan-2-yloxyphenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1OC(C)C)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O BZJKRVBQUMLZIP-WGQQHEPDSA-N 0.000 description 1
• JSAXDUAOMDAEDD-WGQQHEPDSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(2-fluoro-6-propoxyphenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1OCCC)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O JSAXDUAOMDAEDD-WGQQHEPDSA-N 0.000 description 1
• RLALKSLWPQUAEG-NVQRDWNXSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(2-fluorophenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O RLALKSLWPQUAEG-NVQRDWNXSA-N 0.000 description 1
• NXQOQMFSMNSCPI-VBHAUSMQSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(2-methoxy-4-phenylmethoxyphenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1)OCC1=CC=CC=C1)OC)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O NXQOQMFSMNSCPI-VBHAUSMQSA-N 0.000 description 1
• PHRYHWLXMXTIJT-UMCMBGNQSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(2-methoxynaphthalen-1-yl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC2=CC=CC=C12)OC)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O PHRYHWLXMXTIJT-UMCMBGNQSA-N 0.000 description 1
• VRZFJXFTWFGQGO-WVSUBDOOSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(2-methoxyphenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1)OC)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O VRZFJXFTWFGQGO-WVSUBDOOSA-N 0.000 description 1
• RHYFXDWHDCXWOO-AEVYOOLXSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(2-methylsulfanylphenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1)SC)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O RHYFXDWHDCXWOO-AEVYOOLXSA-N 0.000 description 1
• UWPMIWOFXPJRJC-AEVYOOLXSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(2-methylsulfonylphenyl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1)S(=O)(=O)C)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O UWPMIWOFXPJRJC-AEVYOOLXSA-N 0.000 description 1
• ZAAFHUPLYIFRGU-VXHCAWKWSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(3-fluoro-2,5-dimethoxypyridin-4-yl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C(=NC=C1OC)OC)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O ZAAFHUPLYIFRGU-VXHCAWKWSA-N 0.000 description 1
• XPXCREMZWRSHED-NVQRDWNXSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(3-fluoro-5-methoxypyridin-4-yl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=NC=C1OC)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O XPXCREMZWRSHED-NVQRDWNXSA-N 0.000 description 1
• FFYBTRGYJLUQSS-SCFUHWHPSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(3-fluoropyridin-2-yl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=NC=CC=C1F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O FFYBTRGYJLUQSS-SCFUHWHPSA-N 0.000 description 1
• SZPNXSQTMIBNPH-PTGPVQHPSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(5-phenylmethoxypyridin-2-yl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=NC=C(C=C1)OCC1=CC=CC=C1)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O SZPNXSQTMIBNPH-PTGPVQHPSA-N 0.000 description 1
• NOWZSMWGMCACFM-FGSUIDRYSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(5-phenylmethoxypyrimidin-2-yl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=NC=C(C=N1)OCC1=CC=CC=C1)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O NOWZSMWGMCACFM-FGSUIDRYSA-N 0.000 description 1
• UCXVHFSCOJPBAM-CIVUBGFFSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-(5-pyridin-2-ylthiophen-2-yl)ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC=1SC(=CC=1)C1=NC=CC=C1)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O UCXVHFSCOJPBAM-CIVUBGFFSA-N 0.000 description 1
• FDAXWSQNRQNBIO-QTQZEZTPSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-[2-(ethylamino)-6-fluorophenyl]ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1F)NCC)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O FDAXWSQNRQNBIO-QTQZEZTPSA-N 0.000 description 1
• ISHJCQVUWITOQI-NVQRDWNXSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-[2-(trifluoromethoxy)phenyl]ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1)OC(F)(F)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O ISHJCQVUWITOQI-NVQRDWNXSA-N 0.000 description 1
• PXQUJGYOQLZRBF-XLQBYPRFSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-[2-ethylsulfonyl-6-fluoro-4-[(3R)-3-fluoropyrrolidin-1-yl]phenyl]ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1F)N1C[C@@H](CC1)F)S(=O)(=O)CC)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O PXQUJGYOQLZRBF-XLQBYPRFSA-N 0.000 description 1
• QJMAQDNFLPGKKV-JHWBSHPWSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-[2-ethylsulfonyl-6-fluoro-4-[(3R)-3-hydroxypyrrolidin-1-yl]phenyl]ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1F)N1C[C@@H](CC1)O)S(=O)(=O)CC)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O QJMAQDNFLPGKKV-JHWBSHPWSA-N 0.000 description 1
• YWDIZPJIJDGFQP-WVSUBDOOSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-[2-fluoro-6-(2,2,2-trifluoroethoxy)phenyl]ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=CC=C1OCC(F)(F)F)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O YWDIZPJIJDGFQP-WVSUBDOOSA-N 0.000 description 1
• RIZVPBZBCXLDNK-WGQQHEPDSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-[3-(propan-2-ylamino)phenyl]ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=CC(=CC=C1)NC(C)C)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O RIZVPBZBCXLDNK-WGQQHEPDSA-N 0.000 description 1
• CSOSMPCZVLXVGP-QTQZEZTPSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-[4-(dimethylamino)phenyl]ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=CC=C(C=C1)N(C)C)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O CSOSMPCZVLXVGP-QTQZEZTPSA-N 0.000 description 1
• BDBPFOLHPKELAW-QTQZEZTPSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-[4-(ethylamino)-2,6-difluorophenyl]ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=C(C=C(C=C1F)NCC)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O BDBPFOLHPKELAW-QTQZEZTPSA-N 0.000 description 1
• JOGLKVMIZOCUOM-HUBRGWSESA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-[4-(phenoxymethyl)phenyl]ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=CC=C(C=C1)COC1=CC=CC=C1)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O JOGLKVMIZOCUOM-HUBRGWSESA-N 0.000 description 1
• HCNQDRPNGVBCPC-PTGPVQHPSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[2-[4-(pyridin-3-ylmethoxy)phenyl]ethynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=CC=C(C=C1)OCC=1C=NC=CC=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O HCNQDRPNGVBCPC-PTGPVQHPSA-N 0.000 description 1
• SOYXTDSWGFZDRI-WVSUBDOOSA-N 4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-[3-(2-fluorophenyl)prop-1-ynyl]pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CCC1=C(C=CC=C1)F)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O SOYXTDSWGFZDRI-WVSUBDOOSA-N 0.000 description 1
• YFLFOOSHAVPSLP-XUVXKRRUSA-N 4-amino-7-[(2R,4S,5R)-4-hydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]-5-(2-naphthalen-1-ylethynyl)pyrrolo[2,3-d]pyrimidine Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC1=CC=CC2=CC=CC=C12)[C@@H]1O[C@@H]([C@H](C1)O)CNS(N)(=O)=O YFLFOOSHAVPSLP-XUVXKRRUSA-N 0.000 description 1
• HPZBNOIVBCZQRR-UHFFFAOYSA-N 4-ethynyl-3,5-difluoroaniline Chemical compound NC1=CC(F)=C(C#C)C(F)=C1 HPZBNOIVBCZQRR-UHFFFAOYSA-N 0.000 description 1
• JSUGQYILQLIYJH-UHFFFAOYSA-N 4-ethynyl-3-fluoroaniline Chemical compound NC1=CC=C(C#C)C(F)=C1 JSUGQYILQLIYJH-UHFFFAOYSA-N 0.000 description 1
• ZWMAYLMVFSCMMS-UHFFFAOYSA-N 4-ethynyl-n,n-dimethylaniline Chemical compound CN(C)C1=CC=C(C#C)C=C1 ZWMAYLMVFSCMMS-UHFFFAOYSA-N 0.000 description 1
• WRBICKOJBASGMC-UHFFFAOYSA-N 4-ethynylquinoline Chemical compound C1=CC=C2C(C#C)=CC=NC2=C1 WRBICKOJBASGMC-UHFFFAOYSA-N 0.000 description 1
• OCFSQQSXCAUVPA-UHFFFAOYSA-N 4-fluoro-2-methylsulfanylbenzaldehyde Chemical compound CSC1=CC(F)=CC=C1C=O OCFSQQSXCAUVPA-UHFFFAOYSA-N 0.000 description 1
• UZFMOKQJFYMBGY-UHFFFAOYSA-N 4-hydroxy-TEMPO Chemical compound CC1(C)CC(O)CC(C)(C)N1[O] UZFMOKQJFYMBGY-UHFFFAOYSA-N 0.000 description 1
• MNTRRHDQHVKFSS-UHFFFAOYSA-N 4-iodo-3-methylsulfanylphenol Chemical compound CSC1=CC(O)=CC=C1I MNTRRHDQHVKFSS-UHFFFAOYSA-N 0.000 description 1
• LRPCCFSUFGFVBO-UHFFFAOYSA-N 4-iodoisoquinoline Chemical compound C1=CC=C2C(I)=CN=CC2=C1 LRPCCFSUFGFVBO-UHFFFAOYSA-N 0.000 description 1
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
• VRJHQPZVIGNGMX-UHFFFAOYSA-N 4-piperidinone Chemical compound O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 description 1
• 125000006579 5 or 6-membered monocyclic heterocycloalkyl group Chemical group 0.000 description 1
• WDMUELCRMSDBAV-UHFFFAOYSA-N 5-ethynyl-1h-pyrazolo[4,3-b]pyridine Chemical compound C#CC1=CC=C2NN=CC2=N1 WDMUELCRMSDBAV-UHFFFAOYSA-N 0.000 description 1
• GFTBWCMHAKTOJY-UHFFFAOYSA-N 5-ethynylquinoline Chemical compound C1=CC=C2C(C#C)=CC=CC2=N1 GFTBWCMHAKTOJY-UHFFFAOYSA-N 0.000 description 1
• DBGGDAAQLLDHSS-UHFFFAOYSA-N 5-phenylmethoxypyridine-2-carbaldehyde Chemical compound C1=NC(C=O)=CC=C1OCC1=CC=CC=C1 DBGGDAAQLLDHSS-UHFFFAOYSA-N 0.000 description 1
• KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
• YNWXLWZRJNZSGQ-QYVSTXNMSA-N 7-[(3ar,4r,6r,6ar)-6-(aminomethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-5-iodopyrrolo[2,3-d]pyrimidin-4-amine Chemical compound C1=C(I)C2=C(N)N=CN=C2N1[C@@H]1O[C@H](CN)[C@H]2OC(C)(C)O[C@H]21 YNWXLWZRJNZSGQ-QYVSTXNMSA-N 0.000 description 1
• XYRKVWUOLJLIMV-UHFFFAOYSA-N 7-ethynyl-2,3-dihydro-1-benzothiophene 1,1-dioxide Chemical compound C(#C)C1=CC=CC2=C1S(CC2)(=O)=O XYRKVWUOLJLIMV-UHFFFAOYSA-N 0.000 description 1
• WWPIZFWDOMENJP-UHFFFAOYSA-N 7-fluoro-4-methyl-2,3-dihydro-1,4-benzoxazine Chemical compound FC1=CC=C2N(C)CCOC2=C1 WWPIZFWDOMENJP-UHFFFAOYSA-N 0.000 description 1
• FUNBQTYAAUCTPN-UHFFFAOYSA-N 7-methoxyquinoline-8-carbaldehyde Chemical compound C1=CC=NC2=C(C=O)C(OC)=CC=C21 FUNBQTYAAUCTPN-UHFFFAOYSA-N 0.000 description 1
• CSVBAOOXLRAOLW-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine-4-carboxylic acid Chemical compound OC(=O)C1=NC=NC2=C1C=CN2 CSVBAOOXLRAOLW-UHFFFAOYSA-N 0.000 description 1
• DLCWBLXVWDWBEM-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine;hydrochloride Chemical compound Cl.N1=CNC2=NC=CC2=C1 DLCWBLXVWDWBEM-UHFFFAOYSA-N 0.000 description 1
• IYKQLGQHHJTSRT-SPDXLWMLSA-N 8-[2-[4-amino-7-[(1R,2S,3R,4R)-2,3-dihydroxy-4-[(sulfamoylamino)methyl]cyclopentyl]pyrrolo[2,3-d]pyrimidin-5-yl]ethynyl]-7-fluoro-4-methyl-2,3-dihydro-1,4-benzoxazine hydrochloride Chemical compound Cl.CN1CCOc2c1ccc(F)c2C#Cc1cn([C@@H]2C[C@H](CNS(N)(=O)=O)[C@@H](O)[C@H]2O)c2ncnc(N)c12 IYKQLGQHHJTSRT-SPDXLWMLSA-N 0.000 description 1
• VPTZZGXOOMEHBC-UGTJMOTHSA-N 8-[2-[4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidin-5-yl]ethynyl]-7-methoxyquinoline Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC=1C(=CC=C2C=CC=NC=12)OC)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O VPTZZGXOOMEHBC-UGTJMOTHSA-N 0.000 description 1
• BPAKFKNAZQUONR-CIVUBGFFSA-N 8-[2-[4-amino-7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-[(sulfamoylamino)methyl]oxolan-2-yl]pyrrolo[2,3-d]pyrimidin-5-yl]ethynyl]quinoline Chemical compound NC=1C2=C(N=CN=1)N(C=C2C#CC=1C=CC=C2C=CC=NC=12)[C@@H]1O[C@@H]([C@H]([C@H]1O)O)CNS(N)(=O)=O BPAKFKNAZQUONR-CIVUBGFFSA-N 0.000 description 1
• CIHULXDLVAYRMC-UHFFFAOYSA-N 8-ethynyl-7-methoxyquinoline Chemical compound C(#C)C=1C(=CC=C2C=CC=NC=12)OC CIHULXDLVAYRMC-UHFFFAOYSA-N 0.000 description 1
• OBRCQEKKHRCZAP-UHFFFAOYSA-N 8-iodo-3,4-dihydro-2H-thiochromene Chemical compound IC=1C=CC=C2CCCSC=12 OBRCQEKKHRCZAP-UHFFFAOYSA-N 0.000 description 1
• POOPWPIOIMBTOH-UHFFFAOYSA-N 8-oxa-3-azabicyclo[3.2.1]octane Chemical compound C1NCC2CCC1O2 POOPWPIOIMBTOH-UHFFFAOYSA-N 0.000 description 1
• 208000010444 Acidosis Diseases 0.000 description 1
• 208000016683 Adult T-cell leukemia/lymphoma Diseases 0.000 description 1
• 229920001450 Alpha-Cyclodextrin Polymers 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
• 108010011485 Aspartame Proteins 0.000 description 1
• 208000036170 B-Cell Marginal Zone Lymphoma Diseases 0.000 description 1
• 208000025324 B-cell acute lymphoblastic leukemia Diseases 0.000 description 1
• 208000032568 B-cell prolymphocytic leukaemia Diseases 0.000 description 1
• 208000025321 B-lymphoblastic leukemia/lymphoma Diseases 0.000 description 1
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
• 206010005003 Bladder cancer Diseases 0.000 description 1
• IUTCCYSZRLFIQF-UHFFFAOYSA-N BrC1=CC=CC2=C1SCC2.S2C1=C(CC2)C=CC=C1C=O Chemical compound BrC1=CC=CC2=C1SCC2.S2C1=C(CC2)C=CC=C1C=O IUTCCYSZRLFIQF-UHFFFAOYSA-N 0.000 description 1
• TUYBTTLCMSFQFD-UHFFFAOYSA-N BrC1=NC=C(C=N1)O.C(C1=CC=CC=C1)OC=1C=NC(=NC1)Br Chemical compound BrC1=NC=C(C=N1)O.C(C1=CC=CC=C1)OC=1C=NC(=NC1)Br TUYBTTLCMSFQFD-UHFFFAOYSA-N 0.000 description 1
• 208000003174 Brain Neoplasms Diseases 0.000 description 1
• SGHZXLIDFTYFHQ-UHFFFAOYSA-L Brilliant Blue Chemical compound [Na+].[Na+].C=1C=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C(=CC=CC=2)S([O-])(=O)=O)C=CC=1N(CC)CC1=CC=CC(S([O-])(=O)=O)=C1 SGHZXLIDFTYFHQ-UHFFFAOYSA-L 0.000 description 1
• 208000011691 Burkitt lymphomas Diseases 0.000 description 1
• KAKZBPTYRLMSJV-UHFFFAOYSA-N Butadiene Chemical group C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 description 1
• PIBHXHZAEAFZOV-UHFFFAOYSA-N C(#C)C1=C(C=C(C=C1F)N1CCOCC1)F.C(C)OC=1C=C(C=C(C1C#C)F)N1CCOCC1 Chemical compound C(#C)C1=C(C=C(C=C1F)N1CCOCC1)F.C(C)OC=1C=C(C=C(C1C#C)F)N1CCOCC1 PIBHXHZAEAFZOV-UHFFFAOYSA-N 0.000 description 1
• WMGPXZHQPZJXOZ-UHFFFAOYSA-N C(#C)C1=C(C=CC=C1)S(=O)(=O)C Chemical compound C(#C)C1=C(C=CC=C1)S(=O)(=O)C WMGPXZHQPZJXOZ-UHFFFAOYSA-N 0.000 description 1
• HFJUJGZSHMCOBO-UHFFFAOYSA-N C(#C)C=1C=CC=C2CCCS(C=12)(=O)=O Chemical compound C(#C)C=1C=CC=C2CCCS(C=12)(=O)=O HFJUJGZSHMCOBO-UHFFFAOYSA-N 0.000 description 1
• UHWQVCRDUJPCAW-UHFFFAOYSA-N C(C)(C)[Si](C#CC1=C(C=C(C=C1)OC)S(=O)(=O)C)(C(C)C)C(C)C Chemical compound C(C)(C)[Si](C#CC1=C(C=C(C=C1)OC)S(=O)(=O)C)(C(C)C)C(C)C UHWQVCRDUJPCAW-UHFFFAOYSA-N 0.000 description 1
• OIQMDBCNAIOSCC-UHFFFAOYSA-N C(C)SC1=C(C=O)C(=CC(=C1)N1CCCC1)F.C(C)S(=O)(=O)C1=C(C=O)C(=CC(=C1)N1CCCC1)F Chemical compound C(C)SC1=C(C=O)C(=CC(=C1)N1CCCC1)F.C(C)S(=O)(=O)C1=C(C=O)C(=CC(=C1)N1CCCC1)F OIQMDBCNAIOSCC-UHFFFAOYSA-N 0.000 description 1
• LMQDBYKISQTHQO-UHFFFAOYSA-N C(C1=CC=CC=C1)OC=1C=NC(=NC1)Br.C(C1=CC=CC=C1)OC=1C=NC(=NC1)C#C[Si](C(C)C)(C(C)C)C(C)C Chemical compound C(C1=CC=CC=C1)OC=1C=NC(=NC1)Br.C(C1=CC=CC=C1)OC=1C=NC(=NC1)C#C[Si](C(C)C)(C(C)C)C(C)C LMQDBYKISQTHQO-UHFFFAOYSA-N 0.000 description 1
• WBNGVYZOOHJXMK-UHFFFAOYSA-N C(C1=CC=CC=C1)OC=1C=NC(=NC1)C#C[Si](C(C)C)(C(C)C)C(C)C.C(C1=CC=CC=C1)OC=1C=NC(=NC1)C#C Chemical compound C(C1=CC=CC=C1)OC=1C=NC(=NC1)C#C[Si](C(C)C)(C(C)C)C(C)C.C(C1=CC=CC=C1)OC=1C=NC(=NC1)C#C WBNGVYZOOHJXMK-UHFFFAOYSA-N 0.000 description 1
• 208000016778 CD4+/CD56+ hematodermic neoplasm Diseases 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• 206010008342 Cervix carcinoma Diseases 0.000 description 1
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
• 229920000742 Cotton Polymers 0.000 description 1
• 229920002785 Croscarmellose sodium Polymers 0.000 description 1
• CIWBSHSKHKDKBQ-DUZGATOHSA-N D-araboascorbic acid Natural products OC[C@@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-DUZGATOHSA-N 0.000 description 1
• 108020004414 DNA Proteins 0.000 description 1
• XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
• 208000002699 Digestive System Neoplasms Diseases 0.000 description 1
• RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
• 206010013886 Dysaesthesia Diseases 0.000 description 1
• OVBJJZOQPCKUOR-UHFFFAOYSA-L EDTA disodium salt dihydrate Chemical compound O.O.[Na+].[Na+].[O-]C(=O)C[NH+](CC([O-])=O)CC[NH+](CC([O-])=O)CC([O-])=O OVBJJZOQPCKUOR-UHFFFAOYSA-L 0.000 description 1
• 206010014418 Electrolyte imbalance Diseases 0.000 description 1
• 206010014733 Endometrial cancer Diseases 0.000 description 1
• 206010014759 Endometrial neoplasm Diseases 0.000 description 1
• 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
• 108090000371 Esterases Proteins 0.000 description 1
• 239000001856 Ethyl cellulose Substances 0.000 description 1
• ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
• 206010061850 Extranodal marginal zone B-cell lymphoma (MALT type) Diseases 0.000 description 1
• ZHRFJAJETHLUSH-UHFFFAOYSA-N FC1=C(C=O)C(=CC(=C1)N1CCCC1)F.C(C)SC1=C(C=O)C(=CC(=C1)N1CCCC1)F Chemical compound FC1=C(C=O)C(=CC(=C1)N1CCCC1)F.C(C)SC1=C(C=O)C(=CC(=C1)N1CCCC1)F ZHRFJAJETHLUSH-UHFFFAOYSA-N 0.000 description 1
• JGKORGZHETWMCU-UHFFFAOYSA-N FC1=C(C=O)C(=CC=C1)O.C(C)OC1=C(C=O)C(=CC=C1)F Chemical compound FC1=C(C=O)C(=CC=C1)O.C(C)OC1=C(C=O)C(=CC=C1)F JGKORGZHETWMCU-UHFFFAOYSA-N 0.000 description 1
• SINOZUJAGQTJFP-UHFFFAOYSA-N FC1=C(C=O)C(=CC=C1)OC.C(#C)C1=C(C=CC=C1OC)F Chemical compound FC1=C(C=O)C(=CC=C1)OC.C(#C)C1=C(C=CC=C1OC)F SINOZUJAGQTJFP-UHFFFAOYSA-N 0.000 description 1
• ZDGTWMCVKCQIKP-UHFFFAOYSA-N FC1=CC(=C(C=O)C=C1)SC.CSC1=C(C=O)C=CC(=C1)N1CCCCC1 Chemical compound FC1=CC(=C(C=O)C=C1)SC.CSC1=C(C=O)C=CC(=C1)N1CCCCC1 ZDGTWMCVKCQIKP-UHFFFAOYSA-N 0.000 description 1
• SNAKXCNYNCUWLE-UHFFFAOYSA-N FC1=NC=C(C(=C1F)I)F.C(#C)C1=C(C(=NC=C1F)OC)F Chemical compound FC1=NC=C(C(=C1F)I)F.C(#C)C1=C(C(=NC=C1F)OC)F SNAKXCNYNCUWLE-UHFFFAOYSA-N 0.000 description 1
• AXNYRUGEQYVTBJ-UHFFFAOYSA-N FC=1C(=C(C=CC1)O)I.C1(CC1)COC1=C(C(=CC=C1)F)I Chemical compound FC=1C(=C(C=CC1)O)I.C1(CC1)COC1=C(C(=CC=C1)F)I AXNYRUGEQYVTBJ-UHFFFAOYSA-N 0.000 description 1
• FOLMKZKNLRGMQD-UHFFFAOYSA-N FC=1C=C(C#N)C=C(C1C=O)F.C(#C)C1=C(C=C(C(OC)=N)C=C1F)F Chemical compound FC=1C=C(C#N)C=C(C1C=O)F.C(#C)C1=C(C=C(C(OC)=N)C=C1F)F FOLMKZKNLRGMQD-UHFFFAOYSA-N 0.000 description 1
• 208000022072 Gallbladder Neoplasms Diseases 0.000 description 1
• 241000238631 Hexapoda Species 0.000 description 1
• 102100031470 Homeobox protein ARX Human genes 0.000 description 1
• 101000923090 Homo sapiens Homeobox protein ARX Proteins 0.000 description 1
• 101100539455 Homo sapiens NAE1 gene Proteins 0.000 description 1
• 101100371466 Homo sapiens UBA3 gene Proteins 0.000 description 1
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
• 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
• 206010021118 Hypotonia Diseases 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
• 208000008839 Kidney Neoplasms Diseases 0.000 description 1
• 150000000994 L-ascorbates Chemical class 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
• 239000004166 Lanolin Substances 0.000 description 1
• 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 1
• NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 208000028018 Lymphocytic leukaemia Diseases 0.000 description 1
• 201000003791 MALT lymphoma Diseases 0.000 description 1
• 244000024873 Mentha crispa Species 0.000 description 1
• 235000014749 Mentha crispa Nutrition 0.000 description 1
• 206010027406 Mesothelioma Diseases 0.000 description 1
• 206010027417 Metabolic acidosis Diseases 0.000 description 1
• LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
• 229920000881 Modified starch Polymers 0.000 description 1
• 208000007379 Muscle Hypotonia Diseases 0.000 description 1
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
• AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
• JKFOEYTWOKTMGX-AZUPYXJKSA-N NC=1C2=C(N=CN1)N(C=C2I)[C@@H]2O[C@@H]([C@H]1OC(O[C@H]12)(C)C)CO.CO Chemical compound NC=1C2=C(N=CN1)N(C=C2I)[C@@H]2O[C@@H]([C@H]1OC(O[C@H]12)(C)C)CO.CO JKFOEYTWOKTMGX-AZUPYXJKSA-N 0.000 description 1
• 102100020710 NEDD8-conjugating enzyme Ubc12 Human genes 0.000 description 1
• 238000005481 NMR spectroscopy Methods 0.000 description 1
• 208000019569 Nodular lymphocyte predominant Hodgkin lymphoma Diseases 0.000 description 1
• AQPFDHCYVMOUPA-UHFFFAOYSA-N O1CCOCC1.C(#C)C=1C=CC=C2CCCS(C12)(=O)=O Chemical compound O1CCOCC1.C(#C)C=1C=CC=C2CCCS(C12)(=O)=O AQPFDHCYVMOUPA-UHFFFAOYSA-N 0.000 description 1
• 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
• 206010033128 Ovarian cancer Diseases 0.000 description 1
• 206010061535 Ovarian neoplasm Diseases 0.000 description 1
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 229910002666 PdCl2 Inorganic materials 0.000 description 1
• 208000027190 Peripheral T-cell lymphomas Diseases 0.000 description 1
• XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Natural products P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• 239000004698 Polyethylene Substances 0.000 description 1
• 208000004880 Polyuria Diseases 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 208000032758 Precursor T-lymphoblastic lymphoma/leukaemia Diseases 0.000 description 1
• HCBIBCJNVBAKAB-UHFFFAOYSA-N Procaine hydrochloride Chemical compound Cl.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 HCBIBCJNVBAKAB-UHFFFAOYSA-N 0.000 description 1
• 208000035416 Prolymphocytic B-Cell Leukemia Diseases 0.000 description 1
• 206010038389 Renal cancer Diseases 0.000 description 1
• 229920002684 Sepharose Polymers 0.000 description 1
• BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
• DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical class [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 208000005718 Stomach Neoplasms Diseases 0.000 description 1
• 239000004376 Sucralose Substances 0.000 description 1
• 239000012505 Superdex™ Substances 0.000 description 1
• 208000031672 T-Cell Peripheral Lymphoma Diseases 0.000 description 1
• 208000024313 Testicular Neoplasms Diseases 0.000 description 1
• GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
• 102000004357 Transferases Human genes 0.000 description 1
• 108090000992 Transferases Proteins 0.000 description 1
• GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical class OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
• 208000009911 Urinary Calculi Diseases 0.000 description 1
• 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
• BZHJMEDXRYGGRV-UHFFFAOYSA-N Vinyl chloride Chemical compound ClC=C BZHJMEDXRYGGRV-UHFFFAOYSA-N 0.000 description 1
• 229930003427 Vitamin E Natural products 0.000 description 1
• 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 1
• BLTXEPQZAMUGID-ILLHIODVSA-N [(1r,2s,3r,4r)-2,3-dihydroxy-4-(hydroxymethyl)cyclopentyl]azanium;chloride Chemical compound Cl.N[C@@H]1C[C@H](CO)[C@@H](O)[C@H]1O BLTXEPQZAMUGID-ILLHIODVSA-N 0.000 description 1
• 238000009825 accumulation Methods 0.000 description 1
• VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 1
• 150000001242 acetic acid derivatives Chemical class 0.000 description 1
• 239000003377 acid catalyst Substances 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 125000002252 acyl group Chemical group 0.000 description 1
• 102000035181 adaptor proteins Human genes 0.000 description 1
• 108091005764 adaptor proteins Proteins 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 201000006966 adult T-cell leukemia Diseases 0.000 description 1
• 208000015230 aggressive NK-cell leukemia Diseases 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 125000004849 alkoxymethyl group Chemical group 0.000 description 1
• 125000005037 alkyl phenyl group Chemical group 0.000 description 1
• 125000005103 alkyl silyl group Chemical group 0.000 description 1
• 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
• 125000001118 alkylidene group Chemical group 0.000 description 1
• 125000004419 alkynylene group Chemical group 0.000 description 1
• HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 description 1
• 229940043377 alpha-cyclodextrin Drugs 0.000 description 1
• 238000003016 alphascreen Methods 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 229920003144 amino alkyl methacrylate copolymer Polymers 0.000 description 1
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• 229940041181 antineoplastic drug Drugs 0.000 description 1
• 230000006907 apoptotic process Effects 0.000 description 1
• 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
• 125000003710 aryl alkyl group Chemical group 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 239000000605 aspartame Substances 0.000 description 1
• IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
• 235000010357 aspartame Nutrition 0.000 description 1
• 229960003438 aspartame Drugs 0.000 description 1
• 238000003556 assay Methods 0.000 description 1
• GMWFCJXSQQHBPI-UHFFFAOYSA-N azetidin-3-ol Chemical compound OC1CNC1 GMWFCJXSQQHBPI-UHFFFAOYSA-N 0.000 description 1
• 210000003719 b-lymphocyte Anatomy 0.000 description 1
• 229960000686 benzalkonium chloride Drugs 0.000 description 1
• JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical class C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000005872 benzooxazolyl group Chemical group 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
• CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
• 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
• 210000000941 bile Anatomy 0.000 description 1
• AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 description 1
• XGIUDIMNNMKGDE-UHFFFAOYSA-N bis(trimethylsilyl)azanide Chemical compound C[Si](C)(C)[N-][Si](C)(C)C XGIUDIMNNMKGDE-UHFFFAOYSA-N 0.000 description 1
• UORVGPXVDQYIDP-BJUDXGSMSA-N borane Chemical compound [10BH3] UORVGPXVDQYIDP-BJUDXGSMSA-N 0.000 description 1
• 229910000085 borane Inorganic materials 0.000 description 1
• KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
• 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 229960005069 calcium Drugs 0.000 description 1
• 235000001465 calcium Nutrition 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• 239000000378 calcium silicate Substances 0.000 description 1
• 229910052918 calcium silicate Inorganic materials 0.000 description 1
• OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
• 125000002837 carbocyclic group Chemical group 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 229950008138 carmellose Drugs 0.000 description 1
• 235000010418 carrageenan Nutrition 0.000 description 1
• 239000000679 carrageenan Substances 0.000 description 1
• 229920001525 carrageenan Polymers 0.000 description 1
• 229940113118 carrageenan Drugs 0.000 description 1
• 239000012876 carrier material Substances 0.000 description 1
• 239000004359 castor oil Substances 0.000 description 1
• 235000019438 castor oil Nutrition 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 230000022131 cell cycle Effects 0.000 description 1
• 238000012054 celltiter-glo Methods 0.000 description 1
• 230000030570 cellular localization Effects 0.000 description 1
• 201000007455 central nervous system cancer Diseases 0.000 description 1
• 208000025997 central nervous system neoplasm Diseases 0.000 description 1
• 239000007765 cera alba Substances 0.000 description 1
• 201000010881 cervical cancer Diseases 0.000 description 1
• DRKMXSPELWRTIG-UHFFFAOYSA-M cesium chloride heptahydrate Chemical compound O.O.O.O.O.O.O.[Cl-].[Cs+] DRKMXSPELWRTIG-UHFFFAOYSA-M 0.000 description 1
• 229930002875 chlorophyll Natural products 0.000 description 1
• 235000019804 chlorophyll Nutrition 0.000 description 1
• ATNHDLDRLWWWCB-AENOIHSZSA-M chlorophyll a Chemical compound C1([C@@H](C(=O)OC)C(=O)C2=C3C)=C2N2C3=CC(C(CC)=C3C)=[N+]4C3=CC3=C(C=C)C(C)=C5N3[Mg-2]42[N+]2=C1[C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@H](C)C2=C5 ATNHDLDRLWWWCB-AENOIHSZSA-M 0.000 description 1
• 208000006990 cholangiocarcinoma Diseases 0.000 description 1
• 125000005747 chromanylene group Chemical group 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 150000001860 citric acid derivatives Chemical class 0.000 description 1
• 208000013056 classic Hodgkin lymphoma Diseases 0.000 description 1
• 238000003776 cleavage reaction Methods 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 239000012230 colorless oil Substances 0.000 description 1
• 235000009508 confectionery Nutrition 0.000 description 1
• OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 229930003836 cresol Natural products 0.000 description 1
• 229960001681 croscarmellose sodium Drugs 0.000 description 1
• 229960000913 crospovidone Drugs 0.000 description 1
• 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
• 238000012258 culturing Methods 0.000 description 1
• NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 1
• GUDMZGLFZNLYEY-UHFFFAOYSA-N cyclopropylmethanol Chemical compound OCC1CC1 GUDMZGLFZNLYEY-UHFFFAOYSA-N 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 239000011903 deuterated solvents‎ Substances 0.000 description 1
• 238000003745 diagnosis Methods 0.000 description 1
• 238000000502 dialysis Methods 0.000 description 1
• ASWXNYNXAOQCCD-UHFFFAOYSA-N dichloro(triphenyl)-$l^{5}-phosphane Chemical compound C=1C=CC=CC=1P(Cl)(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 ASWXNYNXAOQCCD-UHFFFAOYSA-N 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical class OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
• 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
• 210000002249 digestive system Anatomy 0.000 description 1
• 125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 description 1
• SIPUZPBQZHNSDW-UHFFFAOYSA-N diisobutylaluminium hydride Substances CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
• 238000007865 diluting Methods 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• 201000010099 disease Diseases 0.000 description 1
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
• 229940079593 drug Drugs 0.000 description 1
• 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
• 235000010350 erythorbic acid Nutrition 0.000 description 1
• 239000004318 erythorbic acid Substances 0.000 description 1
• 201000004101 esophageal cancer Diseases 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• 229960004756 ethanol Drugs 0.000 description 1
• 150000002169 ethanolamines Chemical class 0.000 description 1
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
• MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 1
• 235000019325 ethyl cellulose Nutrition 0.000 description 1
• 229920001249 ethyl cellulose Polymers 0.000 description 1
• FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
• 125000006125 ethylsulfonyl group Chemical group 0.000 description 1
• 125000004705 ethylthio group Chemical group C(C)S* 0.000 description 1
• 210000001508 eye Anatomy 0.000 description 1
• 239000003889 eye drop Substances 0.000 description 1
• 229940012356 eye drops Drugs 0.000 description 1
• 239000006260 foam Substances 0.000 description 1
• 201000003444 follicular lymphoma Diseases 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 201000010175 gallbladder cancer Diseases 0.000 description 1
• WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
• 206010017758 gastric cancer Diseases 0.000 description 1
• 229960003180 glutathione Drugs 0.000 description 1
• ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
• 239000006451 grace's insect medium Substances 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 150000008282 halocarbons Chemical class 0.000 description 1
• 201000010536 head and neck cancer Diseases 0.000 description 1
• 208000014829 head and neck neoplasm Diseases 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 102000057307 human UBE2M Human genes 0.000 description 1
• 235000011167 hydrochloric acid Nutrition 0.000 description 1
• 229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
• 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
• 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 239000003999 initiator Substances 0.000 description 1
• 150000007529 inorganic bases Chemical class 0.000 description 1
• 229940030980 inova Drugs 0.000 description 1
• 230000031146 intracellular signal transduction Effects 0.000 description 1
• 238000010253 intravenous injection Methods 0.000 description 1
• 230000026045 iodination Effects 0.000 description 1
• 238000006192 iodination reaction Methods 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
• YOBAEOGBNPPUQV-UHFFFAOYSA-N iron;trihydrate Chemical compound O.O.O.[Fe].[Fe] YOBAEOGBNPPUQV-UHFFFAOYSA-N 0.000 description 1
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical class OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
• 229940026239 isoascorbic acid Drugs 0.000 description 1
• 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000005929 isobutyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])OC(*)=O 0.000 description 1
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
• BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 description 1
• FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 1
• 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
• 230000000155 isotopic effect Effects 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 201000010982 kidney cancer Diseases 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 235000019388 lanolin Nutrition 0.000 description 1
• 229940039717 lanolin Drugs 0.000 description 1
• 229960004194 lidocaine Drugs 0.000 description 1
• 238000002514 liquid chromatography mass spectrum Methods 0.000 description 1
• 229940057995 liquid paraffin Drugs 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 239000012280 lithium aluminium hydride Substances 0.000 description 1
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
• 201000007270 liver cancer Diseases 0.000 description 1
• 208000014018 liver neoplasm Diseases 0.000 description 1
• 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
• 201000011649 lymphoblastic lymphoma Diseases 0.000 description 1
• 239000012139 lysis buffer Substances 0.000 description 1
• 201000000564 macroglobulinemia Diseases 0.000 description 1
• 229910001629 magnesium chloride Inorganic materials 0.000 description 1
• 239000000395 magnesium oxide Substances 0.000 description 1
• CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
• 229960000869 magnesium oxide Drugs 0.000 description 1
• 235000012245 magnesium oxide Nutrition 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
• 235000019341 magnesium sulphate Nutrition 0.000 description 1
• AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
• 150000002688 maleic acid derivatives Chemical class 0.000 description 1
• 230000036210 malignancy Effects 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 230000000873 masking effect Effects 0.000 description 1
• 239000000463 material Substances 0.000 description 1
• 108010082117 matrigel Proteins 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 230000007721 medicinal effect Effects 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
• 229910052753 mercury Inorganic materials 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
• LZSGODWGGHPKDF-UHFFFAOYSA-N methyl 4-ethynyl-3,5-difluorobenzenecarboximidate Chemical compound C(#C)C1=C(C=C(C(OC)=N)C=C1F)F LZSGODWGGHPKDF-UHFFFAOYSA-N 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 150000004702 methyl esters Chemical class 0.000 description 1
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
• 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
• 229960002216 methylparaben Drugs 0.000 description 1
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 235000019799 monosodium phosphate Nutrition 0.000 description 1
• 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
• 208000025113 myeloid leukemia Diseases 0.000 description 1
• 230000002071 myeloproliferative effect Effects 0.000 description 1
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
• XRLJKIYWSQACLG-UHFFFAOYSA-N n-benzyl-4-iodoaniline Chemical compound C1=CC(I)=CC=C1NCC1=CC=CC=C1 XRLJKIYWSQACLG-UHFFFAOYSA-N 0.000 description 1
• 125000006606 n-butoxy group Chemical group 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
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 1
• 239000013642 negative control Substances 0.000 description 1
• 125000005933 neopentyloxycarbonyl group Chemical group 0.000 description 1
• 208000025189 neoplasm of testis Diseases 0.000 description 1
• 150000002823 nitrates Chemical class 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• 208000025275 nodular sclerosis classical Hodgkin lymphoma Diseases 0.000 description 1
• 239000004745 nonwoven fabric Substances 0.000 description 1
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
• URMHMMMIVAECEM-UHFFFAOYSA-N octadecan-9-ol Chemical compound CCCCCCCCCC(O)CCCCCCCC URMHMMMIVAECEM-UHFFFAOYSA-N 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 125000004043 oxo group Chemical group O=* 0.000 description 1
• 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
• 239000003002 pH adjusting agent Substances 0.000 description 1
• 239000006174 pH buffer Substances 0.000 description 1
• 229910052763 palladium Inorganic materials 0.000 description 1
• MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
• PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 208000035824 paresthesia Diseases 0.000 description 1
• 238000005192 partition Methods 0.000 description 1
• 239000006072 paste Substances 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 201000005528 peripheral nervous system neoplasm Diseases 0.000 description 1
• 235000021317 phosphate Nutrition 0.000 description 1
• 150000003003 phosphines Chemical class 0.000 description 1
• 235000011007 phosphoric acid Nutrition 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
• 230000035479 physiological effects, processes and functions Effects 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• BIWOSRSKDCZIFM-UHFFFAOYSA-N piperidin-3-ol Chemical compound OC1CCCNC1 BIWOSRSKDCZIFM-UHFFFAOYSA-N 0.000 description 1
• HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 1
• 125000003367 polycyclic group Chemical group 0.000 description 1
• 229920000573 polyethylene Polymers 0.000 description 1
• 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
• 229940068968 polysorbate 80 Drugs 0.000 description 1
• 229920002635 polyurethane Polymers 0.000 description 1
• 239000004814 polyurethane Substances 0.000 description 1
• 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
• 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 239000013641 positive control Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
• 235000011164 potassium chloride Nutrition 0.000 description 1
• 239000001103 potassium chloride Substances 0.000 description 1
• 239000012286 potassium permanganate Substances 0.000 description 1
• 159000000001 potassium salts Chemical class 0.000 description 1
• 238000002953 preparative HPLC Methods 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical class CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
• 229960001309 procaine hydrochloride Drugs 0.000 description 1
• 230000002062 proliferating effect Effects 0.000 description 1
• NGKSKVYWPINGLI-UHFFFAOYSA-N prop-2-ynylbenzene Chemical compound C#CCC1=CC=CC=C1 NGKSKVYWPINGLI-UHFFFAOYSA-N 0.000 description 1
• UARFKZSJGDQRLF-UHFFFAOYSA-N prop-2-ynylcyclohexane Chemical compound C#CCC1CCCCC1 UARFKZSJGDQRLF-UHFFFAOYSA-N 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
• 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
• 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• 238000010926 purge Methods 0.000 description 1
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000005412 pyrazyl group Chemical group 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• 125000005551 pyridylene group Chemical group 0.000 description 1
• OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 125000005576 pyrimidinylene group Chemical group 0.000 description 1
• WQGWDDDVZFFDIG-UHFFFAOYSA-N pyrogallol Chemical compound OC1=CC=CC(O)=C1O WQGWDDDVZFFDIG-UHFFFAOYSA-N 0.000 description 1
• JAEIBKXSIXOLOL-UHFFFAOYSA-N pyrrolidin-1-ium-3-carboxylate Chemical compound OC(=O)C1CCNC1 JAEIBKXSIXOLOL-UHFFFAOYSA-N 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• 238000006722 reduction reaction Methods 0.000 description 1
• 238000010992 reflux Methods 0.000 description 1
• 238000001226 reprecipitation Methods 0.000 description 1
• 208000015608 reproductive system cancer Diseases 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 201000007048 respiratory system cancer Diseases 0.000 description 1
• 238000004007 reversed phase HPLC Methods 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 235000019204 saccharin Nutrition 0.000 description 1
• 239000000523 sample Substances 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 230000003248 secreting effect Effects 0.000 description 1
• 230000019491 signal transduction Effects 0.000 description 1
• 229910000077 silane Inorganic materials 0.000 description 1
• 239000000741 silica gel Substances 0.000 description 1
• 229910002027 silica gel Inorganic materials 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
• 239000001509 sodium citrate Substances 0.000 description 1
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
• 235000011083 sodium citrates Nutrition 0.000 description 1
• AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
• HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
• 229940037001 sodium edetate Drugs 0.000 description 1
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 229910000104 sodium hydride Inorganic materials 0.000 description 1
• 235000009518 sodium iodide Nutrition 0.000 description 1
• 235000010262 sodium metabisulphite Nutrition 0.000 description 1
• RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• 229940080313 sodium starch Drugs 0.000 description 1
• 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
• 235000010265 sodium sulphite Nutrition 0.000 description 1
• QJDUDPQVDAASMV-UHFFFAOYSA-M sodium;ethanethiolate Chemical compound [Na+].CC[S-] QJDUDPQVDAASMV-UHFFFAOYSA-M 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 229940032147 starch Drugs 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 201000011549 stomach cancer Diseases 0.000 description 1
• 235000019408 sucralose Nutrition 0.000 description 1
• BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
• 150000003871 sulfonates Chemical class 0.000 description 1
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
• 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 150000003892 tartrate salts Chemical class 0.000 description 1
• 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 201000003120 testicular cancer Diseases 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
• 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 125000004149 thio group Chemical group *S* 0.000 description 1
• OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• 125000005559 triazolylene group Chemical group 0.000 description 1
• TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
• 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
• UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical class CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 230000034512 ubiquitination Effects 0.000 description 1
• 238000010798 ubiquitination Methods 0.000 description 1
• 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
• 201000005112 urinary bladder cancer Diseases 0.000 description 1
• 208000008281 urolithiasis Diseases 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 235000019165 vitamin E Nutrition 0.000 description 1
• 229940046009 vitamin E Drugs 0.000 description 1
• 239000011709 vitamin E Substances 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 239000003871 white petrolatum Substances 0.000 description 1
• 239000002759 woven fabric Substances 0.000 description 1
• UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1