MX2012008550A - Derivados de hetaril-[1, 8]naftiridina. - Google Patents

Info

Publication number

MX2012008550A

MX2012008550A MX2012008550A MX2012008550A MX2012008550A MX 2012008550 A MX2012008550 A MX 2012008550A MX 2012008550 A MX2012008550 A MX 2012008550A MX 2012008550 A MX2012008550 A MX 2012008550A MX 2012008550 A MX2012008550 A MX 2012008550A

Authority

MX

Mexico

Prior art keywords

cyy

nyy

phenyl

hal

carbon atoms

Prior art date

2010-02-05

Links

• Espacenet
• Global Dossier
• Discuss

• 238000011282 treatment Methods 0.000 claims abstract description 48
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 45
• 108090000623 proteins and genes Proteins 0.000 claims abstract description 32
• 102000004169 proteins and genes Human genes 0.000 claims abstract description 23
• 239000003112 inhibitor Substances 0.000 claims abstract description 22
• 150000001875 compounds Chemical class 0.000 claims description 228
• -1 boronic acid ester Chemical class 0.000 claims description 217
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 90
• 125000004432 carbon atom Chemical group C* 0.000 claims description 73
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 59
• 150000003839 salts Chemical class 0.000 claims description 59
• 229910052757 nitrogen Inorganic materials 0.000 claims description 51
• 201000010099 disease Diseases 0.000 claims description 50
• 238000000034 method Methods 0.000 claims description 49
• 239000004480 active ingredient Substances 0.000 claims description 35
• 125000001424 substituent group Chemical group 0.000 claims description 34
• 229910052760 oxygen Inorganic materials 0.000 claims description 31
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 28
• 239000001301 oxygen Substances 0.000 claims description 28
• 125000003118 aryl group Chemical group 0.000 claims description 25
• 125000000623 heterocyclic group Chemical group 0.000 claims description 23
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 23
• 229910052717 sulfur Inorganic materials 0.000 claims description 23
• 239000002253 acid Substances 0.000 claims description 22
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 20
• 201000011510 cancer Diseases 0.000 claims description 20
• 150000002148 esters Chemical class 0.000 claims description 20
• 239000011593 sulfur Substances 0.000 claims description 20
• 239000008194 pharmaceutical composition Substances 0.000 claims description 19
• 229920006395 saturated elastomer Polymers 0.000 claims description 17
• 102000004887 Transforming Growth Factor beta Human genes 0.000 claims description 16
• 108090001012 Transforming Growth Factor beta Proteins 0.000 claims description 16
• 239000003814 drug Substances 0.000 claims description 16
• 125000002950 monocyclic group Chemical group 0.000 claims description 16
• 230000008569 process Effects 0.000 claims description 16
• 239000000460 chlorine Substances 0.000 claims description 15
• ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 claims description 15
• 125000001072 heteroaryl group Chemical group 0.000 claims description 14
• 230000001225 therapeutic effect Effects 0.000 claims description 14
• 238000004519 manufacturing process Methods 0.000 claims description 12
• 230000033115 angiogenesis Effects 0.000 claims description 11
• 239000003795 chemical substances by application Substances 0.000 claims description 11
• 229910052801 chlorine Inorganic materials 0.000 claims description 11
• 230000000069 prophylactic effect Effects 0.000 claims description 11
• 125000003342 alkenyl group Chemical group 0.000 claims description 10
• 229910052794 bromium Inorganic materials 0.000 claims description 10
• 229910052731 fluorine Inorganic materials 0.000 claims description 10
• 208000035475 disorder Diseases 0.000 claims description 9
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
• 125000000217 alkyl group Chemical group 0.000 claims description 8
• 125000000304 alkynyl group Chemical group 0.000 claims description 8
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 8
• 206010061218 Inflammation Diseases 0.000 claims description 7
• 239000002671 adjuvant Substances 0.000 claims description 7
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 7
• 230000004054 inflammatory process Effects 0.000 claims description 7
• 229910052740 iodine Inorganic materials 0.000 claims description 7
• 230000029663 wound healing Effects 0.000 claims description 7
• 206010016654 Fibrosis Diseases 0.000 claims description 6
• 125000002947 alkylene group Chemical group 0.000 claims description 6
• 125000002619 bicyclic group Chemical group 0.000 claims description 6
• 210000000988 bone and bone Anatomy 0.000 claims description 6
• 210000003169 central nervous system Anatomy 0.000 claims description 6
• 230000004761 fibrosis Effects 0.000 claims description 6
• 125000004434 sulfur atom Chemical group 0.000 claims description 6
• 201000001320 Atherosclerosis Diseases 0.000 claims description 5
• 208000031886 HIV Infections Diseases 0.000 claims description 5
• 208000037357 HIV infectious disease Diseases 0.000 claims description 5
• 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 5
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 5
• 230000004614 tumor growth Effects 0.000 claims description 5
• 101000777277 Homo sapiens Serine/threonine-protein kinase Chk2 Proteins 0.000 claims description 4
• 108091005682 Receptor kinases Proteins 0.000 claims description 4
• 102100031075 Serine/threonine-protein kinase Chk2 Human genes 0.000 claims description 4
• 125000004429 atom Chemical group 0.000 claims description 4
• 210000000748 cardiovascular system Anatomy 0.000 claims description 4
• 230000006510 metastatic growth Effects 0.000 claims description 4
• 208000037803 restenosis Diseases 0.000 claims description 4
• 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 3
• 230000001028 anti-proliverative effect Effects 0.000 claims description 3
• 239000002834 estrogen receptor modulator Substances 0.000 claims description 3
• 239000004030 hiv protease inhibitor Substances 0.000 claims description 3
• 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 3
• 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 claims description 3
• 102000027483 retinoid hormone receptors Human genes 0.000 claims description 3
• 108091008679 retinoid hormone receptors Proteins 0.000 claims description 3
• 239000003419 rna directed dna polymerase inhibitor Substances 0.000 claims description 3
• 239000000849 selective androgen receptor modulator Substances 0.000 claims description 3
• 239000004037 angiogenesis inhibitor Substances 0.000 claims description 2
• 229940121369 angiogenesis inhibitor Drugs 0.000 claims description 2
• 239000002254 cytotoxic agent Substances 0.000 claims description 2
• 229940127089 cytotoxic agent Drugs 0.000 claims description 2
• 231100000599 cytotoxic agent Toxicity 0.000 claims description 2
• 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
• 102000004357 Transferases Human genes 0.000 claims 1
• 108090000992 Transferases Proteins 0.000 claims 1
• 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 92
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 87
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 63
• 239000011541 reaction mixture Substances 0.000 description 53
• 108091000080 Phosphotransferase Proteins 0.000 description 52
• 102000020233 phosphotransferase Human genes 0.000 description 52
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 51
• 230000015572 biosynthetic process Effects 0.000 description 51
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
• 238000003786 synthesis reaction Methods 0.000 description 42
• 239000000243 solution Substances 0.000 description 39
• 210000004027 cell Anatomy 0.000 description 38
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
• 239000000203 mixture Substances 0.000 description 35
• 150000003254 radicals Chemical class 0.000 description 34
• 102000005962 receptors Human genes 0.000 description 31
• 108020003175 receptors Proteins 0.000 description 31
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 28
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 26
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
• 239000000047 product Substances 0.000 description 26
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
• 239000013078 crystal Substances 0.000 description 23
• 230000011664 signaling Effects 0.000 description 23
• 230000000694 effects Effects 0.000 description 22
• 238000004128 high performance liquid chromatography Methods 0.000 description 22
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
• 239000003446 ligand Substances 0.000 description 21
• 239000002002 slurry Substances 0.000 description 20
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 19
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 19
• 230000005764 inhibitory process Effects 0.000 description 19
• 239000012074 organic phase Substances 0.000 description 19
• 229910052938 sodium sulfate Inorganic materials 0.000 description 19
• 235000011152 sodium sulphate Nutrition 0.000 description 19
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
• 239000002585 base Substances 0.000 description 18
• 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 18
• 239000003480 eluent Substances 0.000 description 18
• 239000000741 silica gel Substances 0.000 description 18
• 229910002027 silica gel Inorganic materials 0.000 description 18
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 17
• 238000006243 chemical reaction Methods 0.000 description 17
• 238000004587 chromatography analysis Methods 0.000 description 16
• 101001106413 Homo sapiens Macrophage-stimulating protein receptor Proteins 0.000 description 14
• 102100021435 Macrophage-stimulating protein receptor Human genes 0.000 description 14
• 238000005481 NMR spectroscopy Methods 0.000 description 14
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 14
• 239000007787 solid Substances 0.000 description 14
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
• 230000019491 signal transduction Effects 0.000 description 13
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 11
• 230000001404 mediated effect Effects 0.000 description 11
• 238000002360 preparation method Methods 0.000 description 11
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 10
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
• 102000001253 Protein Kinase Human genes 0.000 description 10
• 102000009618 Transforming Growth Factors Human genes 0.000 description 10
• 108010009583 Transforming Growth Factors Proteins 0.000 description 10
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 10
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 10
• 238000009472 formulation Methods 0.000 description 10
• 238000006366 phosphorylation reaction Methods 0.000 description 10
• 230000001105 regulatory effect Effects 0.000 description 10
• 239000000126 substance Substances 0.000 description 10
• 238000012360 testing method Methods 0.000 description 10
• 101100490437 Mus musculus Acvrl1 gene Proteins 0.000 description 9
• 238000005755 formation reaction Methods 0.000 description 9
• 230000026731 phosphorylation Effects 0.000 description 9
• 108060006633 protein kinase Proteins 0.000 description 9
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
• 235000017557 sodium bicarbonate Nutrition 0.000 description 9
• 239000002904 solvent Substances 0.000 description 9
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
• KPZYAGQLBFUTMA-UHFFFAOYSA-K tripotassium;phosphate;trihydrate Chemical compound O.O.O.[K+].[K+].[K+].[O-]P([O-])([O-])=O KPZYAGQLBFUTMA-UHFFFAOYSA-K 0.000 description 9
• 102100028448 Nuclear receptor subfamily 2 group C member 2 Human genes 0.000 description 8
• 230000018109 developmental process Effects 0.000 description 8
• 230000003993 interaction Effects 0.000 description 8
• 238000012544 monitoring process Methods 0.000 description 8
• 239000003921 oil Substances 0.000 description 8
• 235000019198 oils Nutrition 0.000 description 8
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
• 239000000651 prodrug Substances 0.000 description 8
• 229940002612 prodrug Drugs 0.000 description 8
• 230000004044 response Effects 0.000 description 8
• 239000000758 substrate Substances 0.000 description 8
• 108091008743 testicular receptors 4 Proteins 0.000 description 8
• 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 7
• 238000003556 assay Methods 0.000 description 7
• 125000005488 carboaryl group Chemical group 0.000 description 7
• 125000000753 cycloalkyl group Chemical group 0.000 description 7
• 238000011161 development Methods 0.000 description 7
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
• 235000019253 formic acid Nutrition 0.000 description 7
• 239000007924 injection Substances 0.000 description 7
• 238000002347 injection Methods 0.000 description 7
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
• 230000001575 pathological effect Effects 0.000 description 7
• 230000035755 proliferation Effects 0.000 description 7
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 7
• 239000012453 solvate Substances 0.000 description 7
• 208000024891 symptom Diseases 0.000 description 7
• 238000002560 therapeutic procedure Methods 0.000 description 7
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
• 208000026310 Breast neoplasm Diseases 0.000 description 6
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
• 241001465754 Metazoa Species 0.000 description 6
• 102100025751 Mothers against decapentaplegic homolog 2 Human genes 0.000 description 6
• 101710143123 Mothers against decapentaplegic homolog 2 Proteins 0.000 description 6
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
• CAWQOMFOSDRVLD-UHFFFAOYSA-N [2-(5-chloro-2-fluorophenyl)-1,8-naphthyridin-4-yl]boronic acid Chemical compound N=1C2=NC=CC=C2C(B(O)O)=CC=1C1=CC(Cl)=CC=C1F CAWQOMFOSDRVLD-UHFFFAOYSA-N 0.000 description 6
• 239000012267 brine Substances 0.000 description 6
• 239000003054 catalyst Substances 0.000 description 6
• 230000006870 function Effects 0.000 description 6
• 238000000338 in vitro Methods 0.000 description 6
• 229940043355 kinase inhibitor Drugs 0.000 description 6
• 210000004072 lung Anatomy 0.000 description 6
• 230000007246 mechanism Effects 0.000 description 6
• 239000000546 pharmaceutical excipient Substances 0.000 description 6
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 6
• 238000001959 radiotherapy Methods 0.000 description 6
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
• 239000007858 starting material Substances 0.000 description 6
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
• KNYLMSGZBZMLSJ-UHFFFAOYSA-N 4-(5-bromopyridin-3-yl)-2-(5-chloro-2-fluorophenyl)-1,8-naphthyridine Chemical compound FC1=CC=C(Cl)C=C1C1=CC(C=2C=C(Br)C=NC=2)=C(C=CC=N2)C2=N1 KNYLMSGZBZMLSJ-UHFFFAOYSA-N 0.000 description 5
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
• RYVZYACBVYKUHD-UHFFFAOYSA-N Alk5 Natural products CC#CC#CCCCCC=CC(=O)NCC(C)C RYVZYACBVYKUHD-UHFFFAOYSA-N 0.000 description 5
• 208000005623 Carcinogenesis Diseases 0.000 description 5
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
• 102000004190 Enzymes Human genes 0.000 description 5
• 108090000790 Enzymes Proteins 0.000 description 5
• 241000124008 Mammalia Species 0.000 description 5
• 206010027476 Metastases Diseases 0.000 description 5
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 5
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
• 108091005735 TGF-beta receptors Proteins 0.000 description 5
• 102000016715 Transforming Growth Factor beta Receptors Human genes 0.000 description 5
• 230000033228 biological regulation Effects 0.000 description 5
• 230000036952 cancer formation Effects 0.000 description 5
• 231100000504 carcinogenesis Toxicity 0.000 description 5
• 125000004122 cyclic group Chemical group 0.000 description 5
• 210000002919 epithelial cell Anatomy 0.000 description 5
• 230000014509 gene expression Effects 0.000 description 5
• 229910052736 halogen Inorganic materials 0.000 description 5
• 238000010438 heat treatment Methods 0.000 description 5
• 238000001727 in vivo Methods 0.000 description 5
• 208000015181 infectious disease Diseases 0.000 description 5
• 239000000543 intermediate Substances 0.000 description 5
• 239000007788 liquid Substances 0.000 description 5
• 230000009401 metastasis Effects 0.000 description 5
• 230000035772 mutation Effects 0.000 description 5
• 239000003208 petroleum Substances 0.000 description 5
• 125000003367 polycyclic group Chemical group 0.000 description 5
• 210000003491 skin Anatomy 0.000 description 5
• 229910000029 sodium carbonate Inorganic materials 0.000 description 5
• 238000006467 substitution reaction Methods 0.000 description 5
• 239000000725 suspension Substances 0.000 description 5
• 210000001519 tissue Anatomy 0.000 description 5
• FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 4
• WJNJSWJJGQDCCF-UHFFFAOYSA-N 4-chloro-2-(5-chloro-2-fluorophenyl)-1,8-naphthyridine Chemical compound FC1=CC=C(Cl)C=C1C1=CC(Cl)=C(C=CC=N2)C2=N1 WJNJSWJJGQDCCF-UHFFFAOYSA-N 0.000 description 4
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
• 102100022014 Angiopoietin-1 receptor Human genes 0.000 description 4
• 206010006187 Breast cancer Diseases 0.000 description 4
• 102100032813 Hepatocyte growth factor-like protein Human genes 0.000 description 4
• 101000753291 Homo sapiens Angiopoietin-1 receptor Proteins 0.000 description 4
• 241000699670 Mus sp. Species 0.000 description 4
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 4
• 229910019142 PO4 Inorganic materials 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
• 238000001994 activation Methods 0.000 description 4
• 238000006254 arylation reaction Methods 0.000 description 4
• 230000037396 body weight Effects 0.000 description 4
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
• 238000004113 cell culture Methods 0.000 description 4
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
• 229940079593 drug Drugs 0.000 description 4
• 210000002889 endothelial cell Anatomy 0.000 description 4
• 230000003176 fibrotic effect Effects 0.000 description 4
• 239000000706 filtrate Substances 0.000 description 4
• 210000003780 hair follicle Anatomy 0.000 description 4
• 150000002367 halogens Chemical class 0.000 description 4
• 229930195733 hydrocarbon Natural products 0.000 description 4
• 239000004615 ingredient Substances 0.000 description 4
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 4
• 210000004185 liver Anatomy 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• 239000002609 medium Substances 0.000 description 4
• 239000002207 metabolite Substances 0.000 description 4
• 230000005012 migration Effects 0.000 description 4
• 238000013508 migration Methods 0.000 description 4
• 230000002018 overexpression Effects 0.000 description 4
• 235000021317 phosphate Nutrition 0.000 description 4
• SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
• 230000000644 propagated effect Effects 0.000 description 4
• 238000011321 prophylaxis Methods 0.000 description 4
• 125000003226 pyrazolyl group Chemical group 0.000 description 4
• JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
• 125000004076 pyridyl group Chemical group 0.000 description 4
• 102000027426 receptor tyrosine kinases Human genes 0.000 description 4
• 108091008598 receptor tyrosine kinases Proteins 0.000 description 4
• 230000009467 reduction Effects 0.000 description 4
• 230000002829 reductive effect Effects 0.000 description 4
• 238000010992 reflux Methods 0.000 description 4
• 230000001177 retroviral effect Effects 0.000 description 4
• 238000007363 ring formation reaction Methods 0.000 description 4
• 230000004083 survival effect Effects 0.000 description 4
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 4
• 230000002792 vascular Effects 0.000 description 4
• LVIRZMJTRPDFGU-UHFFFAOYSA-N 1-(2-pyrrolidin-1-ylethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole Chemical compound O1C(C)(C)C(C)(C)OB1C1=CN(CCN2CCCC2)N=C1 LVIRZMJTRPDFGU-UHFFFAOYSA-N 0.000 description 3
• 125000004809 1-methylpropylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])C([H])([H])[*:2] 0.000 description 3
• IKWDAKSBNHWBNW-UHFFFAOYSA-N 2-(5-chloro-2-fluorophenyl)-4-(6-chloropyrazin-2-yl)-1,8-naphthyridine Chemical compound FC1=CC=C(Cl)C=C1C1=CC(C=2N=C(Cl)C=NC=2)=C(C=CC=N2)C2=N1 IKWDAKSBNHWBNW-UHFFFAOYSA-N 0.000 description 3
• QLEPIXIMTMBVMQ-UHFFFAOYSA-N 3-bromo-5-(1-methylpyrazol-4-yl)pyridine Chemical compound C1=NN(C)C=C1C1=CN=CC(Br)=C1 QLEPIXIMTMBVMQ-UHFFFAOYSA-N 0.000 description 3
• AOOZLVWDZUPEHT-UHFFFAOYSA-N 3-bromo-5-iodopyridine Chemical compound BrC1=CN=CC(I)=C1 AOOZLVWDZUPEHT-UHFFFAOYSA-N 0.000 description 3
• SIADAGFXEHBPGG-UHFFFAOYSA-N 4-chloro-1,8-naphthyridine Chemical compound C1=CC=C2C(Cl)=CC=NC2=N1 SIADAGFXEHBPGG-UHFFFAOYSA-N 0.000 description 3
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 3
• 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 3
• CVICEEPAFUYBJG-UHFFFAOYSA-N 5-chloro-2,2-difluoro-1,3-benzodioxole Chemical group C1=C(Cl)C=C2OC(F)(F)OC2=C1 CVICEEPAFUYBJG-UHFFFAOYSA-N 0.000 description 3
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• 102100034134 Activin receptor type-1B Human genes 0.000 description 3
• 108010059616 Activins Proteins 0.000 description 3
• 102000009840 Angiopoietins Human genes 0.000 description 3
• 108010009906 Angiopoietins Proteins 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• 101150006084 CHKB gene Proteins 0.000 description 3
• 239000004215 Carbon black (E152) Substances 0.000 description 3
• QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
• 201000009030 Carcinoma Diseases 0.000 description 3
• 206010009944 Colon cancer Diseases 0.000 description 3
• 102100031111 Disintegrin and metalloproteinase domain-containing protein 17 Human genes 0.000 description 3
• 102100037241 Endoglin Human genes 0.000 description 3
• 102100031983 Ephrin type-B receptor 4 Human genes 0.000 description 3
• 101000799189 Homo sapiens Activin receptor type-1B Proteins 0.000 description 3
• 101001066435 Homo sapiens Hepatocyte growth factor-like protein Proteins 0.000 description 3
• 101000609532 Homo sapiens Phosphoinositide-3-kinase-interacting protein 1 Proteins 0.000 description 3
• 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 3
• 102100026818 Inhibin beta E chain Human genes 0.000 description 3
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
• 102100025725 Mothers against decapentaplegic homolog 4 Human genes 0.000 description 3
• 101710143112 Mothers against decapentaplegic homolog 4 Proteins 0.000 description 3
• 241000700159 Rattus Species 0.000 description 3
• 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 3
• 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 3
• 150000007513 acids Chemical class 0.000 description 3
• 230000004913 activation Effects 0.000 description 3
• 239000013543 active substance Substances 0.000 description 3
• 239000000488 activin Substances 0.000 description 3
• 150000001298 alcohols Chemical class 0.000 description 3
• 230000009286 beneficial effect Effects 0.000 description 3
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 3
• 230000004071 biological effect Effects 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
• 239000002775 capsule Substances 0.000 description 3
• 230000004663 cell proliferation Effects 0.000 description 3
• 230000033077 cellular process Effects 0.000 description 3
• 230000005754 cellular signaling Effects 0.000 description 3
• 230000008859 change Effects 0.000 description 3
• 210000001072 colon Anatomy 0.000 description 3
• 230000002950 deficient Effects 0.000 description 3
• 230000001419 dependent effect Effects 0.000 description 3
• 239000011737 fluorine Substances 0.000 description 3
• 230000012010 growth Effects 0.000 description 3
• 230000026030 halogenation Effects 0.000 description 3
• 238000005658 halogenation reaction Methods 0.000 description 3
• 125000005842 heteroatom Chemical group 0.000 description 3
• 229910052739 hydrogen Inorganic materials 0.000 description 3
• 239000001257 hydrogen Substances 0.000 description 3
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
• 125000002883 imidazolyl group Chemical group 0.000 description 3
• 230000001976 improved effect Effects 0.000 description 3
• 230000000415 inactivating effect Effects 0.000 description 3
• 239000012442 inert solvent Substances 0.000 description 3
• 230000002401 inhibitory effect Effects 0.000 description 3
• 239000011630 iodine Substances 0.000 description 3
• GDTOUTKTCGPAGY-UHFFFAOYSA-N isoquinolin-4-ylboronic acid Chemical compound C1=CC=C2C(B(O)O)=CN=CC2=C1 GDTOUTKTCGPAGY-UHFFFAOYSA-N 0.000 description 3
• 210000003734 kidney Anatomy 0.000 description 3
• 238000012423 maintenance Methods 0.000 description 3
• 239000000463 material Substances 0.000 description 3
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
• 150000005054 naphthyridines Chemical class 0.000 description 3
• 235000001968 nicotinic acid Nutrition 0.000 description 3
• 239000011664 nicotinic acid Substances 0.000 description 3
• 150000007524 organic acids Chemical class 0.000 description 3
• 150000007530 organic bases Chemical class 0.000 description 3
• 230000036961 partial effect Effects 0.000 description 3
• 230000037361 pathway Effects 0.000 description 3
• 239000012071 phase Substances 0.000 description 3
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
• 239000010452 phosphate Substances 0.000 description 3
• 230000035790 physiological processes and functions Effects 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• 108090000765 processed proteins & peptides Proteins 0.000 description 3
• 125000000714 pyrimidinyl group Chemical group 0.000 description 3
• 230000002285 radioactive effect Effects 0.000 description 3
• 125000006413 ring segment Chemical group 0.000 description 3
• 230000002195 synergetic effect Effects 0.000 description 3
• 239000000454 talc Substances 0.000 description 3
• 235000012222 talc Nutrition 0.000 description 3
• 229910052623 talc Inorganic materials 0.000 description 3
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
• 125000004306 triazinyl group Chemical group 0.000 description 3
• 241001430294 unidentified retrovirus Species 0.000 description 3
• 210000003932 urinary bladder Anatomy 0.000 description 3
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 2
• CCQHBZIXZFQYSO-UHFFFAOYSA-N 2,4-dichloro-1,8-naphthyridine Chemical compound C1=CC=NC2=NC(Cl)=CC(Cl)=C21 CCQHBZIXZFQYSO-UHFFFAOYSA-N 0.000 description 2
• TUKWURGQYVAAMJ-UHFFFAOYSA-N 2-(4-chloro-1,8-naphthyridin-2-yl)benzamide Chemical compound NC(=O)C1=CC=CC=C1C1=CC(Cl)=C(C=CC=N2)C2=N1 TUKWURGQYVAAMJ-UHFFFAOYSA-N 0.000 description 2
• IHVLIAZTRYFGPK-UHFFFAOYSA-N 2-(4-chloro-1,8-naphthyridin-2-yl)benzonitrile Chemical compound N=1C2=NC=CC=C2C(Cl)=CC=1C1=CC=CC=C1C#N IHVLIAZTRYFGPK-UHFFFAOYSA-N 0.000 description 2
• FCKYTQUFUXOVQQ-UHFFFAOYSA-N 2-(5-chloro-2-fluorophenyl)-4-(5-phenylpyridin-3-yl)-1,8-naphthyridine Chemical compound FC1=CC=C(Cl)C=C1C1=CC(C=2C=C(C=NC=2)C=2C=CC=CC=2)=C(C=CC=N2)C2=N1 FCKYTQUFUXOVQQ-UHFFFAOYSA-N 0.000 description 2
• IDGCGUWIEHPFAV-UHFFFAOYSA-N 2-(5-chloro-2-fluorophenyl)-4-[5-(4-piperazin-1-ylphenyl)pyridin-3-yl]-1,8-naphthyridine Chemical compound FC1=CC=C(Cl)C=C1C1=CC(C=2C=C(C=NC=2)C=2C=CC(=CC=2)N2CCNCC2)=C(C=CC=N2)C2=N1 IDGCGUWIEHPFAV-UHFFFAOYSA-N 0.000 description 2
• DJQRVGPXRBKZMT-UHFFFAOYSA-N 2-(5-chloro-2-fluorophenyl)-4-[5-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]pyridin-3-yl]-1,8-naphthyridine Chemical compound C1CN(C)CCN1C1=CC=C(C=2C=C(C=NC=2)C=2C3=CC=CN=C3N=C(C=2)C=2C(=CC=C(Cl)C=2)F)C=N1 DJQRVGPXRBKZMT-UHFFFAOYSA-N 0.000 description 2
• ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
• JXCNGEGHNRVCDW-UHFFFAOYSA-N 2-[5-[2-(5-chloro-2-fluorophenyl)-1,8-naphthyridin-4-yl]pyridin-3-yl]ethynyl-triethylsilane Chemical compound CC[Si](CC)(CC)C#CC1=CN=CC(C=2C3=CC=CN=C3N=C(C=2)C=2C(=CC=C(Cl)C=2)F)=C1 JXCNGEGHNRVCDW-UHFFFAOYSA-N 0.000 description 2
• 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 2
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 2
• HABSXVJHFZUIQW-UHFFFAOYSA-N 3-bromo-5-(1-methylpyrazol-4-yl)-1-oxidopyridin-1-ium Chemical compound C1=NN(C)C=C1C1=CC(Br)=C[N+]([O-])=C1 HABSXVJHFZUIQW-UHFFFAOYSA-N 0.000 description 2
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 2
• 102100037263 3-phosphoinositide-dependent protein kinase 1 Human genes 0.000 description 2
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
• TYPNTNMYUCVLIL-UHFFFAOYSA-N 4-bromo-2-(5-chloro-2-fluorophenyl)quinoline Chemical compound FC1=CC=C(Cl)C=C1C1=CC(Br)=C(C=CC=C2)C2=N1 TYPNTNMYUCVLIL-UHFFFAOYSA-N 0.000 description 2
• FSHTWRUAGYMCQQ-UHFFFAOYSA-N 4-chloro-2-(6-methylpyridin-2-yl)-1,8-naphthyridine Chemical compound CC1=CC=CC(C=2N=C3N=CC=CC3=C(Cl)C=2)=N1 FSHTWRUAGYMCQQ-UHFFFAOYSA-N 0.000 description 2
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
• 102100034111 Activin receptor type-1 Human genes 0.000 description 2
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
• 208000024172 Cardiovascular disease Diseases 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
• 229910021595 Copper(I) iodide Inorganic materials 0.000 description 2
• 102000004127 Cytokines Human genes 0.000 description 2
• 108090000695 Cytokines Proteins 0.000 description 2
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
• 238000012286 ELISA Assay Methods 0.000 description 2
• 108010036395 Endoglin Proteins 0.000 description 2
• 102100023721 Ephrin-B2 Human genes 0.000 description 2
• 108010044090 Ephrin-B2 Proteins 0.000 description 2
• YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 2
• 241000711549 Hepacivirus C Species 0.000 description 2
• 101000600756 Homo sapiens 3-phosphoinositide-dependent protein kinase 1 Proteins 0.000 description 2
• 101000799140 Homo sapiens Activin receptor type-1 Proteins 0.000 description 2
• 101000777461 Homo sapiens Disintegrin and metalloproteinase domain-containing protein 17 Proteins 0.000 description 2
• 101000979342 Homo sapiens Nuclear factor NF-kappa-B p105 subunit Proteins 0.000 description 2
• 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 2
• 101001117146 Homo sapiens [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial Proteins 0.000 description 2
• 125000002842 L-seryl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])O[H] 0.000 description 2
• 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 2
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
• 102100025748 Mothers against decapentaplegic homolog 3 Human genes 0.000 description 2
• 101710143111 Mothers against decapentaplegic homolog 3 Proteins 0.000 description 2
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 2
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
• 150000001204 N-oxides Chemical class 0.000 description 2
• 229910002651 NO3 Inorganic materials 0.000 description 2
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
• 102100023050 Nuclear factor NF-kappa-B p105 subunit Human genes 0.000 description 2
• 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 2
• 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 2
• 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
• 108010029485 Protein Isoforms Proteins 0.000 description 2
• 102000001708 Protein Isoforms Human genes 0.000 description 2
• 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 2
• 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 2
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 2
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 2
• 206010064911 Pulmonary arterial hypertension Diseases 0.000 description 2
• 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 2
• 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 description 2
• 108020004459 Small interfering RNA Proteins 0.000 description 2
• 238000006619 Stille reaction Methods 0.000 description 2
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
• 102000040945 Transcription factor Human genes 0.000 description 2
• 108091023040 Transcription factor Proteins 0.000 description 2
• 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 2
• 241000700605 Viruses Species 0.000 description 2
• 206010052428 Wound Diseases 0.000 description 2
• 208000027418 Wounds and injury Diseases 0.000 description 2
• 230000002159 abnormal effect Effects 0.000 description 2
• 239000012345 acetylating agent Substances 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 239000000654 additive Substances 0.000 description 2
• 229910052783 alkali metal Inorganic materials 0.000 description 2
• 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
• 150000001340 alkali metals Chemical class 0.000 description 2
• 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 2
• 150000004703 alkoxides Chemical class 0.000 description 2
• 150000001408 amides Chemical class 0.000 description 2
• 230000002491 angiogenic effect Effects 0.000 description 2
• 150000001448 anilines Chemical class 0.000 description 2
• 239000002246 antineoplastic agent Substances 0.000 description 2
• 239000003963 antioxidant agent Substances 0.000 description 2
• 235000006708 antioxidants Nutrition 0.000 description 2
• 238000013459 approach Methods 0.000 description 2
• 239000008346 aqueous phase Substances 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• 150000005840 aryl radicals Chemical class 0.000 description 2
• RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 2
• 229910001863 barium hydroxide Inorganic materials 0.000 description 2
• 230000008901 benefit Effects 0.000 description 2
• 229940077388 benzenesulfonate Drugs 0.000 description 2
• 229940050390 benzoate Drugs 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• 239000004305 biphenyl Substances 0.000 description 2
• 235000010290 biphenyl Nutrition 0.000 description 2
• 230000000903 blocking effect Effects 0.000 description 2
• 210000004369 blood Anatomy 0.000 description 2
• 239000008280 blood Substances 0.000 description 2
• 210000004204 blood vessel Anatomy 0.000 description 2
• 201000008275 breast carcinoma Diseases 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• YSHOWEKUVWPFNR-UHFFFAOYSA-N burgess reagent Chemical compound CC[N+](CC)(CC)S(=O)(=O)N=C([O-])OC YSHOWEKUVWPFNR-UHFFFAOYSA-N 0.000 description 2
• AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 2
• 239000000920 calcium hydroxide Substances 0.000 description 2
• 229910001861 calcium hydroxide Inorganic materials 0.000 description 2
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
• 230000003778 catagen phase Effects 0.000 description 2
• 230000030833 cell death Effects 0.000 description 2
• 230000010261 cell growth Effects 0.000 description 2
• 210000003679 cervix uteri Anatomy 0.000 description 2
• 239000003153 chemical reaction reagent Substances 0.000 description 2
• BFPSDSIWYFKGBC-UHFFFAOYSA-N chlorotrianisene Chemical compound C1=CC(OC)=CC=C1C(Cl)=C(C=1C=CC(OC)=CC=1)C1=CC=C(OC)C=C1 BFPSDSIWYFKGBC-UHFFFAOYSA-N 0.000 description 2
• LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 2
• 230000008878 coupling Effects 0.000 description 2
• 238000010168 coupling process Methods 0.000 description 2
• 238000005859 coupling reaction Methods 0.000 description 2
• 230000009260 cross reactivity Effects 0.000 description 2
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
• 238000003745 diagnosis Methods 0.000 description 2
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 2
• 230000004069 differentiation Effects 0.000 description 2
• SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
• 239000006196 drop Substances 0.000 description 2
• 239000000975 dye Substances 0.000 description 2
• 230000002526 effect on cardiovascular system Effects 0.000 description 2
• 230000008030 elimination Effects 0.000 description 2
• 238000003379 elimination reaction Methods 0.000 description 2
• 230000013020 embryo development Effects 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 238000005516 engineering process Methods 0.000 description 2
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 2
• 238000000605 extraction Methods 0.000 description 2
• 239000012530 fluid Substances 0.000 description 2
• 238000002875 fluorescence polarization Methods 0.000 description 2
• 125000001153 fluoro group Chemical group F* 0.000 description 2
• 239000006260 foam Substances 0.000 description 2
• 125000002541 furyl group Chemical group 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 230000009036 growth inhibition Effects 0.000 description 2
• 230000002140 halogenating effect Effects 0.000 description 2
• 210000000987 immune system Anatomy 0.000 description 2
• 230000036039 immunity Effects 0.000 description 2
• 230000001506 immunosuppresive effect Effects 0.000 description 2
• 230000006872 improvement Effects 0.000 description 2
• 230000006698 induction Effects 0.000 description 2
• 208000027866 inflammatory disease Diseases 0.000 description 2
• 230000002757 inflammatory effect Effects 0.000 description 2
• 239000013067 intermediate product Substances 0.000 description 2
• 230000003834 intracellular effect Effects 0.000 description 2
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
• 230000004060 metabolic process Effects 0.000 description 2
• QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 125000002757 morpholinyl group Chemical group 0.000 description 2
• 210000000214 mouth Anatomy 0.000 description 2
• 125000001624 naphthyl group Chemical group 0.000 description 2
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• 210000002569 neuron Anatomy 0.000 description 2
• 229960003512 nicotinic acid Drugs 0.000 description 2
• LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
• 230000008520 organization Effects 0.000 description 2
• 125000001715 oxadiazolyl group Chemical group 0.000 description 2
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
• 210000000496 pancreas Anatomy 0.000 description 2
• 238000007911 parenteral administration Methods 0.000 description 2
• 230000000865 phosphorylative effect Effects 0.000 description 2
• 125000004193 piperazinyl group Chemical group 0.000 description 2
• 125000003386 piperidinyl group Chemical group 0.000 description 2
• 229910052700 potassium Inorganic materials 0.000 description 2
• 239000011591 potassium Substances 0.000 description 2
• 235000011056 potassium acetate Nutrition 0.000 description 2
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
• RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 2
• 229920001592 potato starch Polymers 0.000 description 2
• 230000003389 potentiating effect Effects 0.000 description 2
• 238000001556 precipitation Methods 0.000 description 2
• 239000002243 precursor Substances 0.000 description 2
• 102000004196 processed proteins & peptides Human genes 0.000 description 2
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
• 210000002307 prostate Anatomy 0.000 description 2
• 125000003373 pyrazinyl group Chemical group 0.000 description 2
• 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 description 2
• 125000002098 pyridazinyl group Chemical group 0.000 description 2
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
• 238000011160 research Methods 0.000 description 2
• 230000002441 reversible effect Effects 0.000 description 2
• 238000007127 saponification reaction Methods 0.000 description 2
• 239000012047 saturated solution Substances 0.000 description 2
• 238000012216 screening Methods 0.000 description 2
• 238000000926 separation method Methods 0.000 description 2
• 239000004055 small Interfering RNA Substances 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• RCOSUMRTSQULBK-UHFFFAOYSA-N sodium;propan-1-olate Chemical compound [Na+].CCC[O-] RCOSUMRTSQULBK-UHFFFAOYSA-N 0.000 description 2
• 241000894007 species Species 0.000 description 2
• 239000007921 spray Substances 0.000 description 2
• 230000006641 stabilisation Effects 0.000 description 2
• 238000011105 stabilization Methods 0.000 description 2
• 210000000130 stem cell Anatomy 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 230000001629 suppression Effects 0.000 description 2
• 208000011580 syndromic disease Diseases 0.000 description 2
• DCQGWRXQFFUGBZ-UHFFFAOYSA-N tert-butyl 4-[4-(5-bromopyridin-3-yl)pyrazol-1-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1N1N=CC(C=2C=C(Br)C=NC=2)=C1 DCQGWRXQFFUGBZ-UHFFFAOYSA-N 0.000 description 2
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
• 150000003606 tin compounds Chemical class 0.000 description 2
• 230000000699 topical effect Effects 0.000 description 2
• 239000003558 transferase inhibitor Substances 0.000 description 2
• 230000007704 transition Effects 0.000 description 2
• URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
• 125000001425 triazolyl group Chemical group 0.000 description 2
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
• 230000007998 vessel formation Effects 0.000 description 2
• 230000037314 wound repair Effects 0.000 description 2
• LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
• NPLZNDDFVCGRAG-UHFFFAOYSA-N (2-cyanophenyl)boronic acid Chemical compound OB(O)C1=CC=CC=C1C#N NPLZNDDFVCGRAG-UHFFFAOYSA-N 0.000 description 1
• FVWWKNZKPWWOCF-UHFFFAOYSA-N (5-phenylpyridin-3-yl)boronic acid Chemical compound OB(O)C1=CN=CC(C=2C=CC=CC=2)=C1 FVWWKNZKPWWOCF-UHFFFAOYSA-N 0.000 description 1
• YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 1
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
• 125000005919 1,2,2-trimethylpropyl group Chemical group 0.000 description 1
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
• BNVLGAQNNFJKHG-UHFFFAOYSA-N 1-(2-aminopyridin-3-yl)ethanone Chemical compound CC(=O)C1=CC=CN=C1N BNVLGAQNNFJKHG-UHFFFAOYSA-N 0.000 description 1
• FSNGFFWICFYWQC-UHFFFAOYSA-N 1-(2-chloroethyl)pyrrolidine;hydron;chloride Chemical compound Cl.ClCCN1CCCC1 FSNGFFWICFYWQC-UHFFFAOYSA-N 0.000 description 1
• YWRBLSYOLXMZGA-UHFFFAOYSA-N 1-[2-(oxan-2-yloxy)ethyl]-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole Chemical compound O1C(C)(C)C(C)(C)OB1C1=CN(CCOC2OCCCC2)N=C1 YWRBLSYOLXMZGA-UHFFFAOYSA-N 0.000 description 1
• 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
• 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
• 125000006218 1-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
• PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 1
• PRLTVODJPCFDHW-UHFFFAOYSA-N 1-methyl-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]piperidine Chemical compound C1CN(C)CCC1N1N=CC(B2OC(C)(C)C(C)(C)O2)=C1 PRLTVODJPCFDHW-UHFFFAOYSA-N 0.000 description 1
• 125000004837 1-methylpentylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
• 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 description 1
• KYWXRBNOYGGPIZ-UHFFFAOYSA-N 1-morpholin-4-ylethanone Chemical compound CC(=O)N1CCOCC1 KYWXRBNOYGGPIZ-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
• 238000005160 1H NMR spectroscopy Methods 0.000 description 1
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
• IYPFQEMKOBRMII-UHFFFAOYSA-N 1h-1,8-naphthyridine-2,4-dione Chemical compound C1=CN=C2NC(=O)CC(=O)C2=C1 IYPFQEMKOBRMII-UHFFFAOYSA-N 0.000 description 1
• LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 1
• 125000004825 2,2-dimethylpropylene group Chemical group [H]C([H])([H])C(C([H])([H])[H])(C([H])([H])[*:1])C([H])([H])[*:2] 0.000 description 1
• HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
• 125000005808 2,4,6-trimethoxyphenyl group Chemical group [H][#6]-1=[#6](-[#8]C([H])([H])[H])-[#6](-*)=[#6](-[#8]C([H])([H])[H])-[#6]([H])=[#6]-1-[#8]C([H])([H])[H] 0.000 description 1
• NIFORZSTQWZJEB-UHFFFAOYSA-N 2,4-dioxo-4a,5,6,7-tetrahydro-1H-1,8-naphthyridine-3-carboxylic acid Chemical class N1C(C(C(C2CCCN=C12)=O)C(=O)O)=O NIFORZSTQWZJEB-UHFFFAOYSA-N 0.000 description 1
• LSEAAPGIZCDEEH-UHFFFAOYSA-N 2,6-dichloropyrazine Chemical compound ClC1=CN=CC(Cl)=N1 LSEAAPGIZCDEEH-UHFFFAOYSA-N 0.000 description 1
• JNLNRENRMLSKSC-UHFFFAOYSA-N 2-(2,5-difluorophenyl)-4-[5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-3-yl]-1,8-naphthyridine Chemical compound FC1=CC=C(F)C(C=2N=C3N=CC=CC3=C(C=3C=C(C=NC=3)C3=CN(N=C3)C3CCNCC3)C=2)=C1 JNLNRENRMLSKSC-UHFFFAOYSA-N 0.000 description 1
• GCUOLJOTJRUDIZ-UHFFFAOYSA-N 2-(2-bromoethoxy)oxane Chemical compound BrCCOC1CCCCO1 GCUOLJOTJRUDIZ-UHFFFAOYSA-N 0.000 description 1
• XUNWYDXCHWIDLB-UHFFFAOYSA-N 2-(2-fluorophenyl)-4-(2,7-naphthyridin-4-yl)-1,8-naphthyridine Chemical compound FC1=CC=CC=C1C1=CC(C=2C3=CC=NC=C3C=NC=2)=C(C=CC=N2)C2=N1 XUNWYDXCHWIDLB-UHFFFAOYSA-N 0.000 description 1
• KRUMSPHTGIPCHG-UHFFFAOYSA-N 2-(2-fluorophenyl)-4-(5-pyrazol-1-ylpyridin-3-yl)-1,8-naphthyridine Chemical compound FC1=CC=CC=C1C1=CC(C=2C=C(C=NC=2)N2N=CC=C2)=C(C=CC=N2)C2=N1 KRUMSPHTGIPCHG-UHFFFAOYSA-N 0.000 description 1
• LWAQEVAXAYHSHV-UHFFFAOYSA-N 2-(2-fluorophenyl)-4-[5-(1-methylpyrazol-3-yl)pyridin-3-yl]-1,8-naphthyridine Chemical compound CN1C=CC(C=2C=C(C=NC=2)C=2C3=CC=CN=C3N=C(C=2)C=2C(=CC=CC=2)F)=N1 LWAQEVAXAYHSHV-UHFFFAOYSA-N 0.000 description 1
• JBGGWJILKVFWPK-UHFFFAOYSA-N 2-(2-fluorophenyl)-4-[5-(1-piperidin-4-ylpyrazol-4-yl)pyridin-3-yl]-1,8-naphthyridine;dihydrochloride Chemical compound Cl.Cl.FC1=CC=CC=C1C1=CC(C=2C=C(C=NC=2)C2=CN(N=C2)C2CCNCC2)=C(C=CC=N2)C2=N1 JBGGWJILKVFWPK-UHFFFAOYSA-N 0.000 description 1
• BXIZMEPXMZSFKS-UHFFFAOYSA-N 2-(2-fluorophenyl)-4-[5-(2-methylpyrazol-3-yl)pyridin-3-yl]-1,8-naphthyridine Chemical compound CN1N=CC=C1C1=CN=CC(C=2C3=CC=CN=C3N=C(C=2)C=2C(=CC=CC=2)F)=C1 BXIZMEPXMZSFKS-UHFFFAOYSA-N 0.000 description 1
• GOFMNEGVYWWQLF-UHFFFAOYSA-N 2-(2-fluorophenyl)-4-[5-(4-piperazin-1-ylpyrimidin-2-yl)pyridin-3-yl]-1,8-naphthyridine Chemical compound FC1=CC=CC=C1C1=CC(C=2C=C(C=NC=2)C=2N=C(C=CN=2)N2CCNCC2)=C(C=CC=N2)C2=N1 GOFMNEGVYWWQLF-UHFFFAOYSA-N 0.000 description 1
• CRWSVCVMXVUHHL-UHFFFAOYSA-N 2-(2-fluorophenyl)-4-[6-(6-piperazin-1-ylpyridin-3-yl)pyrazin-2-yl]-1,8-naphthyridine Chemical compound FC1=CC=CC=C1C1=CC(C=2N=C(C=NC=2)C=2C=NC(=CC=2)N2CCNCC2)=C(C=CC=N2)C2=N1 CRWSVCVMXVUHHL-UHFFFAOYSA-N 0.000 description 1
• KBMNJDKQPXWOIA-UHFFFAOYSA-N 2-(3-chlorophenyl)-4-[5-(1-methylpyrazol-4-yl)pyridin-3-yl]-1,8-naphthyridine Chemical compound C1=NN(C)C=C1C1=CN=CC(C=2C3=CC=CN=C3N=C(C=2)C=2C=C(Cl)C=CC=2)=C1 KBMNJDKQPXWOIA-UHFFFAOYSA-N 0.000 description 1
• UIIHSNXDPRYORQ-UHFFFAOYSA-N 2-(4-fluorophenyl)-4-[5-(1-methylpyrazol-4-yl)pyridin-3-yl]-1,8-naphthyridine Chemical compound C1=NN(C)C=C1C1=CN=CC(C=2C3=CC=CN=C3N=C(C=2)C=2C=CC(F)=CC=2)=C1 UIIHSNXDPRYORQ-UHFFFAOYSA-N 0.000 description 1
• DFPCEQVYPJPHLN-UHFFFAOYSA-N 2-(5-chloro-2-fluorophenyl)-4-isoquinolin-4-yl-1,8-naphthyridine Chemical compound FC1=CC=C(Cl)C=C1C1=CC(C=2C3=CC=CC=C3C=NC=2)=C(C=CC=N2)C2=N1 DFPCEQVYPJPHLN-UHFFFAOYSA-N 0.000 description 1
• HUPNKZAOFPTFPH-UHFFFAOYSA-N 2-(5-chloro-2-fluorophenyl)-4-isoquinolin-4-ylquinoline Chemical compound FC1=CC=C(Cl)C=C1C1=CC(C=2C3=CC=CC=C3C=NC=2)=C(C=CC=C2)C2=N1 HUPNKZAOFPTFPH-UHFFFAOYSA-N 0.000 description 1
• PCAHMCWDULHCCL-UHFFFAOYSA-N 2-(6-methylpyridin-2-yl)-1h-1,8-naphthyridin-4-one Chemical compound CC1=CC=CC(C=2NC3=NC=CC=C3C(=O)C=2)=N1 PCAHMCWDULHCCL-UHFFFAOYSA-N 0.000 description 1
• XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical group COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
• CKIJYJVMZUJYMN-UHFFFAOYSA-N 2-[2-fluoro-5-(trifluoromethyl)phenyl]-4-[5-(1-methylpyrazol-4-yl)pyridin-3-yl]-1,8-naphthyridine Chemical compound C1=NN(C)C=C1C1=CN=CC(C=2C3=CC=CN=C3N=C(C=2)C=2C(=CC=C(C=2)C(F)(F)F)F)=C1 CKIJYJVMZUJYMN-UHFFFAOYSA-N 0.000 description 1
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
• CEHVSPABGZUTTH-UHFFFAOYSA-N 2-[4-[5-[2-(5-chloro-2-fluorophenyl)-1,8-naphthyridin-4-yl]pyridin-3-yl]pyrazol-1-yl]-n-methylethanamine Chemical compound C1=NN(CCNC)C=C1C1=CN=CC(C=2C3=CC=CN=C3N=C(C=2)C=2C(=CC=C(Cl)C=2)F)=C1 CEHVSPABGZUTTH-UHFFFAOYSA-N 0.000 description 1
• HEQOJEGTZCTHCF-UHFFFAOYSA-N 2-amino-1-phenylethanone Chemical compound NCC(=O)C1=CC=CC=C1 HEQOJEGTZCTHCF-UHFFFAOYSA-N 0.000 description 1
• LLKRSJVPTKFSLS-UHFFFAOYSA-N 2-bromo-5-iodopyridine Chemical compound BrC1=CC=C(I)C=N1 LLKRSJVPTKFSLS-UHFFFAOYSA-N 0.000 description 1
• 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 1
• 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
• 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
• LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
• 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
• 125000004838 2-methylpentylene group Chemical group [H]C([H])([H])C([H])(C([H])([H])[*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
• 125000004810 2-methylpropylene group Chemical group [H]C([H])([H])C([H])(C([H])([H])[*:2])C([H])([H])[*:1] 0.000 description 1
• 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
• 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
• JGABMVVOXLQCKZ-UHFFFAOYSA-N 2-phenyl-1h-quinolin-4-one Chemical compound N=1C2=CC=CC=C2C(O)=CC=1C1=CC=CC=C1 JGABMVVOXLQCKZ-UHFFFAOYSA-N 0.000 description 1
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 125000004362 3,4,5-trichlorophenyl group Chemical group [H]C1=C(Cl)C(Cl)=C(Cl)C([H])=C1* 0.000 description 1
• 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 description 1
• HFZIZUJPOHOYGZ-UHFFFAOYSA-N 3-(1-methylpyrazol-4-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine Chemical compound C1=NN(C)C=C1C1=CN=CC(B2OC(C)(C)C(C)(C)O2)=C1 HFZIZUJPOHOYGZ-UHFFFAOYSA-N 0.000 description 1
• KYNOJKGKMGDSRV-UHFFFAOYSA-N 3-bromo-5-[2-(5-chloro-2-fluorophenyl)-1,8-naphthyridin-4-yl]pyridin-2-amine Chemical compound C1=C(Br)C(N)=NC=C1C1=CC(C=2C(=CC=C(Cl)C=2)F)=NC2=NC=CC=C12 KYNOJKGKMGDSRV-UHFFFAOYSA-N 0.000 description 1
• 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
• 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
• 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
• ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical compound OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
• 125000006027 3-methyl-1-butenyl group Chemical group 0.000 description 1
• 125000004820 3-methylbutylene group Chemical group [H]C([H])([H])C([H])(C([H])([H])[*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
• 125000004839 3-methylpentylene group Chemical group [H]C([H])([H])C([H])(C([H])([H])C([H])([H])[*:1])C([H])([H])C([H])([H])[*:2] 0.000 description 1
• XMIIGOLPHOKFCH-UHFFFAOYSA-M 3-phenylpropionate Chemical compound [O-]C(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-M 0.000 description 1
• LMWJMOHZHSSLAJ-UHFFFAOYSA-N 4-(5-bromopyridin-3-yl)-2-(2-fluorophenyl)-1,8-naphthyridine Chemical compound FC1=CC=CC=C1C1=CC(C=2C=C(Br)C=NC=2)=C(C=CC=N2)C2=N1 LMWJMOHZHSSLAJ-UHFFFAOYSA-N 0.000 description 1
• FRIUEYZPYVPOKU-UHFFFAOYSA-N 4-(5-bromopyridin-3-yl)-2-(3-methylpyrazol-1-yl)-1,8-naphthyridine Chemical compound N1=C(C)C=CN1C1=CC(C=2C=C(Br)C=NC=2)=C(C=CC=N2)C2=N1 FRIUEYZPYVPOKU-UHFFFAOYSA-N 0.000 description 1
• HWMAYVYTAGIQPM-UHFFFAOYSA-N 4-[2-(2,5-difluorophenyl)-1,8-naphthyridin-4-yl]-2,7-naphthyridin-1-amine Chemical compound C12=CC=NC=C2C(N)=NC=C1C(C1=CC=CN=C1N=1)=CC=1C1=CC(F)=CC=C1F HWMAYVYTAGIQPM-UHFFFAOYSA-N 0.000 description 1
• YSJCOMNEMMCZAM-UHFFFAOYSA-N 4-[2-(2-fluorophenyl)-1,8-naphthyridin-4-yl]-2,7-naphthyridin-1-amine Chemical compound C12=CC=NC=C2C(N)=NC=C1C(C1=CC=CN=C1N=1)=CC=1C1=CC=CC=C1F YSJCOMNEMMCZAM-UHFFFAOYSA-N 0.000 description 1
• JWNJUADYCWPFHO-UHFFFAOYSA-N 4-[5-(1-methylpyrazol-4-yl)pyridin-3-yl]-2-(2,4,5-trifluorophenyl)-1,8-naphthyridine Chemical compound C1=NN(C)C=C1C1=CN=CC(C=2C3=CC=CN=C3N=C(C=2)C=2C(=CC(F)=C(F)C=2)F)=C1 JWNJUADYCWPFHO-UHFFFAOYSA-N 0.000 description 1
• PGEPPHPURVGMQH-UHFFFAOYSA-N 4-[5-(1-methylpyrazol-4-yl)pyridin-3-yl]-2-(6-methylpyridin-2-yl)-1,8-naphthyridine Chemical compound CC1=CC=CC(C=2N=C3N=CC=CC3=C(C=3C=C(C=NC=3)C3=CN(C)N=C3)C=2)=N1 PGEPPHPURVGMQH-UHFFFAOYSA-N 0.000 description 1
• XGLYHSLHVDLCDZ-UHFFFAOYSA-N 4-[5-(1-methylpyrazol-4-yl)pyridin-3-yl]-2-[3-(trifluoromethyl)phenyl]-1,8-naphthyridine Chemical compound C1=NN(C)C=C1C1=CN=CC(C=2C3=CC=CN=C3N=C(C=2)C=2C=C(C=CC=2)C(F)(F)F)=C1 XGLYHSLHVDLCDZ-UHFFFAOYSA-N 0.000 description 1
• NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 1
• HCQHVQSQHXZRGA-UHFFFAOYSA-N 4-bromo-2-phenylpyridine Chemical compound BrC1=CC=NC(C=2C=CC=CC=2)=C1 HCQHVQSQHXZRGA-UHFFFAOYSA-N 0.000 description 1
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
• SUXIPCHEUMEUSV-UHFFFAOYSA-N 4-bromoquinoline Chemical compound C1=CC=C2C(Br)=CC=NC2=C1 SUXIPCHEUMEUSV-UHFFFAOYSA-N 0.000 description 1
• JFCJQSAXTPXNGO-UHFFFAOYSA-N 4-chloro-2-(2,4,5-trifluorophenyl)-1,8-naphthyridine Chemical compound C1=C(F)C(F)=CC(F)=C1C1=CC(Cl)=C(C=CC=N2)C2=N1 JFCJQSAXTPXNGO-UHFFFAOYSA-N 0.000 description 1
• LXACYMGZHCJFRE-UHFFFAOYSA-N 4-chloro-2-(2,5-difluorophenyl)-1,8-naphthyridine Chemical compound FC1=CC=C(F)C(C=2N=C3N=CC=CC3=C(Cl)C=2)=C1 LXACYMGZHCJFRE-UHFFFAOYSA-N 0.000 description 1
• WZKWIPOLSCLGLU-UHFFFAOYSA-N 4-chloro-2-(2-fluorophenyl)-1,8-naphthyridine Chemical compound FC1=CC=CC=C1C1=CC(Cl)=C(C=CC=N2)C2=N1 WZKWIPOLSCLGLU-UHFFFAOYSA-N 0.000 description 1
• XZVJQTNKZMMCBT-UHFFFAOYSA-N 4-chloro-2-(3-chlorophenyl)-1,8-naphthyridine Chemical compound ClC1=CC=CC(C=2N=C3N=CC=CC3=C(Cl)C=2)=C1 XZVJQTNKZMMCBT-UHFFFAOYSA-N 0.000 description 1
• HOYNYTRQKHBCHV-UHFFFAOYSA-N 4-chloro-2-(4-fluorophenyl)-1,8-naphthyridine Chemical compound C1=CC(F)=CC=C1C1=CC(Cl)=C(C=CC=N2)C2=N1 HOYNYTRQKHBCHV-UHFFFAOYSA-N 0.000 description 1
• PFPMYGSUANWCKG-UHFFFAOYSA-N 4-chloro-2-[2-fluoro-5-(trifluoromethoxy)phenyl]-1,8-naphthyridine Chemical compound FC1=CC=C(OC(F)(F)F)C=C1C1=CC(Cl)=C(C=CC=N2)C2=N1 PFPMYGSUANWCKG-UHFFFAOYSA-N 0.000 description 1
• KYDQATARRBDECO-UHFFFAOYSA-N 4-chloro-2-[2-fluoro-5-(trifluoromethyl)phenyl]-1,8-naphthyridine Chemical compound FC1=CC=C(C(F)(F)F)C=C1C1=CC(Cl)=C(C=CC=N2)C2=N1 KYDQATARRBDECO-UHFFFAOYSA-N 0.000 description 1
• MRFPJLFNJDOIDP-UHFFFAOYSA-N 4-chloro-2-[3-(trifluoromethyl)phenyl]-1,8-naphthyridine Chemical compound FC(F)(F)C1=CC=CC(C=2N=C3N=CC=CC3=C(Cl)C=2)=C1 MRFPJLFNJDOIDP-UHFFFAOYSA-N 0.000 description 1
• LUORZZNCJWKOSX-UHFFFAOYSA-N 4-hydroxy-1h-1,8-naphthyridin-2-one Chemical compound C1=CN=C2NC(O)=CC(=O)C2=C1 LUORZZNCJWKOSX-UHFFFAOYSA-N 0.000 description 1
• 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 description 1
• AJBAUBRIKAVPRS-UHFFFAOYSA-N 4-isoquinolin-4-yl-2-(6-methylpyridin-2-yl)-1,8-naphthyridine Chemical compound CC1=CC=CC(C=2N=C3N=CC=CC3=C(C=3C4=CC=CC=C4C=NC=3)C=2)=N1 AJBAUBRIKAVPRS-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
• 125000004840 4-methylpentylene group Chemical group [H]C([H])([H])C([H])(C([H])([H])[*:2])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
• BPJJMJUMQALUSL-UHFFFAOYSA-N 4a,5,6,7-tetrahydro-1H-1,8-naphthyridine-2,4-dione Chemical class N1C(CC(C2CCCN=C12)=O)=O BPJJMJUMQALUSL-UHFFFAOYSA-N 0.000 description 1
• IXYHUKXKWZXVDK-UHFFFAOYSA-N 5-[2-(2-fluorophenyl)-1,8-naphthyridin-4-yl]-2,7-naphthyridin-1-amine Chemical compound C1=NC=C2C(N)=NC=CC2=C1C(C1=CC=CN=C1N=1)=CC=1C1=CC=CC=C1F IXYHUKXKWZXVDK-UHFFFAOYSA-N 0.000 description 1
• VOJINZWFQWTAIC-UHFFFAOYSA-N 5-[2-(5-chloro-2-fluorophenyl)-1,8-naphthyridin-4-yl]-3-(1-methylpyrazol-4-yl)pyridin-2-amine Chemical compound C1=NN(C)C=C1C1=CC(C=2C3=CC=CN=C3N=C(C=2)C=2C(=CC=C(Cl)C=2)F)=CN=C1N VOJINZWFQWTAIC-UHFFFAOYSA-N 0.000 description 1
• NAEBEXMHMLDQLZ-UHFFFAOYSA-N 5-[2-(5-chloro-2-fluorophenyl)-1,8-naphthyridin-4-yl]pyridin-2-amine Chemical compound C1=NC(N)=CC=C1C1=CC(C=2C(=CC=C(Cl)C=2)F)=NC2=NC=CC=C12 NAEBEXMHMLDQLZ-UHFFFAOYSA-N 0.000 description 1
• WGOLHUGPTDEKCF-UHFFFAOYSA-N 5-bromopyridin-2-amine Chemical compound NC1=CC=C(Br)C=N1 WGOLHUGPTDEKCF-UHFFFAOYSA-N 0.000 description 1
• VWGAATKTEAKOCO-UHFFFAOYSA-N 5-chloro-2-fluorobenzoyl chloride Chemical compound FC1=CC=C(Cl)C=C1C(Cl)=O VWGAATKTEAKOCO-UHFFFAOYSA-N 0.000 description 1
• SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 description 1
• 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 description 1
• FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
• 108091007505 ADAM17 Proteins 0.000 description 1
• 208000030507 AIDS Diseases 0.000 description 1
• RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
• 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
• 108700028369 Alleles Proteins 0.000 description 1
• 208000024827 Alzheimer disease Diseases 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• 208000023275 Autoimmune disease Diseases 0.000 description 1
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
• ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
• 206010055113 Breast cancer metastatic Diseases 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
• 125000006519 CCH3 Chemical group 0.000 description 1
• 101150041968 CDC13 gene Proteins 0.000 description 1
• 101100220616 Caenorhabditis elegans chk-2 gene Proteins 0.000 description 1
• 101100407060 Caenorhabditis elegans par-6 gene Proteins 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 102000014914 Carrier Proteins Human genes 0.000 description 1
• 108010078791 Carrier Proteins Proteins 0.000 description 1
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
• 208000027932 Collagen disease Diseases 0.000 description 1
• 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
• 208000002330 Congenital Heart Defects Diseases 0.000 description 1
• 241000699800 Cricetinae Species 0.000 description 1
• RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
• 230000005778 DNA damage Effects 0.000 description 1
• 231100000277 DNA damage Toxicity 0.000 description 1
• 101150096494 DYRK2 gene Proteins 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 206010012689 Diabetic retinopathy Diseases 0.000 description 1
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
• 102100031480 Dual specificity mitogen-activated protein kinase kinase 1 Human genes 0.000 description 1
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
• 238000008157 ELISA kit Methods 0.000 description 1
• 102000050554 Eph Family Receptors Human genes 0.000 description 1
• 108091008815 Eph receptors Proteins 0.000 description 1
• 108010055196 EphA2 Receptor Proteins 0.000 description 1
• 108010055334 EphB2 Receptor Proteins 0.000 description 1
• 102100030340 Ephrin type-A receptor 2 Human genes 0.000 description 1
• 102100031968 Ephrin type-B receptor 2 Human genes 0.000 description 1
• 241000283086 Equidae Species 0.000 description 1
• 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
• 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
• 102000007665 Extracellular Signal-Regulated MAP Kinases Human genes 0.000 description 1
• 108010007457 Extracellular Signal-Regulated MAP Kinases Proteins 0.000 description 1
• GGCJCOZODURXPI-UHFFFAOYSA-N FC1=C(C=CC=C1)C1=NC2=NC=CC=C2C(=C1)C1=CN=C(C2=CN=CC=C12)CC(=O)N Chemical compound FC1=C(C=CC=C1)C1=NC2=NC=CC=C2C(=C1)C1=CN=C(C2=CN=CC=C12)CC(=O)N GGCJCOZODURXPI-UHFFFAOYSA-N 0.000 description 1
• 108091008794 FGF receptors Proteins 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 1
• 102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 description 1
• 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• 102100037813 Focal adhesion kinase 1 Human genes 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
• 102000013446 GTP Phosphohydrolases Human genes 0.000 description 1
• 108091006109 GTPases Proteins 0.000 description 1
• DSLZVSRJTYRBFB-UHFFFAOYSA-N Galactaric acid Natural products OC(=O)C(O)C(O)C(O)C(O)C(O)=O DSLZVSRJTYRBFB-UHFFFAOYSA-N 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 206010018338 Glioma Diseases 0.000 description 1
• 101710155270 Glycerate 2-kinase Proteins 0.000 description 1
• 108010090290 Growth Differentiation Factor 2 Proteins 0.000 description 1
• 102100040892 Growth/differentiation factor 2 Human genes 0.000 description 1
• 239000007995 HEPES buffer Substances 0.000 description 1
• 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 1
• 102000003745 Hepatocyte Growth Factor Human genes 0.000 description 1
• 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 1
• 108010033040 Histones Proteins 0.000 description 1
• 238000003692 Hiyama coupling reaction Methods 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101001014196 Homo sapiens Dual specificity mitogen-activated protein kinase kinase 1 Proteins 0.000 description 1
• 101000938354 Homo sapiens Ephrin type-A receptor 1 Proteins 0.000 description 1
• 101000878536 Homo sapiens Focal adhesion kinase 1 Proteins 0.000 description 1
• 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 1
• 101001034652 Homo sapiens Insulin-like growth factor 1 receptor Proteins 0.000 description 1
• 101000573441 Homo sapiens Misshapen-like kinase 1 Proteins 0.000 description 1
• 101000628949 Homo sapiens Mitogen-activated protein kinase 10 Proteins 0.000 description 1
• 101001001487 Homo sapiens Phosphatidylinositol-glycan biosynthesis class F protein Proteins 0.000 description 1
• 101000595923 Homo sapiens Placenta growth factor Proteins 0.000 description 1
• 101000944909 Homo sapiens Ribosomal protein S6 kinase alpha-1 Proteins 0.000 description 1
• 101000851018 Homo sapiens Vascular endothelial growth factor receptor 1 Proteins 0.000 description 1
• 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 1
• 101000851030 Homo sapiens Vascular endothelial growth factor receptor 3 Proteins 0.000 description 1
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• 206010062016 Immunosuppression Diseases 0.000 description 1
• 102100021854 Inhibitor of nuclear factor kappa-B kinase subunit beta Human genes 0.000 description 1
• 101710205525 Inhibitor of nuclear factor kappa-B kinase subunit beta Proteins 0.000 description 1
• 108010001127 Insulin Receptor Proteins 0.000 description 1
• 102100036721 Insulin receptor Human genes 0.000 description 1
• 102000008070 Interferon-gamma Human genes 0.000 description 1
• 108010074328 Interferon-gamma Proteins 0.000 description 1
• LNQCUTNLHUQZLR-VNPYQEQNSA-N Iridin Natural products O(C)c1c(O)c2C(=O)C(c3cc(OC)c(OC)c(O)c3)=COc2cc1O[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1 LNQCUTNLHUQZLR-VNPYQEQNSA-N 0.000 description 1
• VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 1
• 108090000769 Isomerases Proteins 0.000 description 1
• 102000004195 Isomerases Human genes 0.000 description 1
• 101150009057 JAK2 gene Proteins 0.000 description 1
• 108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 description 1
• 102000019145 JUN kinase activity proteins Human genes 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
• 101150081525 LIMK1 gene Proteins 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
• 229910021380 Manganese Chloride Inorganic materials 0.000 description 1
• GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• 102100026287 Misshapen-like kinase 1 Human genes 0.000 description 1
• 102100026931 Mitogen-activated protein kinase 10 Human genes 0.000 description 1
• 102100028192 Mitogen-activated protein kinase kinase kinase kinase 2 Human genes 0.000 description 1
• 101710144533 Mitogen-activated protein kinase kinase kinase kinase 2 Proteins 0.000 description 1
• 108010006519 Molecular Chaperones Proteins 0.000 description 1
• 102000005431 Molecular Chaperones Human genes 0.000 description 1
• 102100025744 Mothers against decapentaplegic homolog 1 Human genes 0.000 description 1
• 102100030610 Mothers against decapentaplegic homolog 5 Human genes 0.000 description 1
• 101710143113 Mothers against decapentaplegic homolog 5 Proteins 0.000 description 1
• 241000699666 Mus <mouse, genus> Species 0.000 description 1
• 241000699660 Mus musculus Species 0.000 description 1
• 101100268066 Mus musculus Zap70 gene Proteins 0.000 description 1
• 108010083674 Myelin Proteins Proteins 0.000 description 1
• 102000006386 Myelin Proteins Human genes 0.000 description 1
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
• ONXPDKGXOOORHB-BYPYZUCNSA-N N(5)-methyl-L-glutamine Chemical compound CNC(=O)CC[C@H](N)C(O)=O ONXPDKGXOOORHB-BYPYZUCNSA-N 0.000 description 1
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
• AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 1
• QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 1
• AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 1
• 238000006411 Negishi coupling reaction Methods 0.000 description 1
• 241000772415 Neovison vison Species 0.000 description 1
• 206010029260 Neuroblastoma Diseases 0.000 description 1
• 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
• 102000007399 Nuclear hormone receptor Human genes 0.000 description 1
• 108020005497 Nuclear hormone receptor Proteins 0.000 description 1
• 108091028043 Nucleic acid sequence Proteins 0.000 description 1
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
• 102000015636 Oligopeptides Human genes 0.000 description 1
• 108010038807 Oligopeptides Proteins 0.000 description 1
• 108700020796 Oncogene Proteins 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 101710160107 Outer membrane protein A Proteins 0.000 description 1
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
• 108091008606 PDGF receptors Proteins 0.000 description 1
• 108091007960 PI3Ks Proteins 0.000 description 1
• 102000038030 PI3Ks Human genes 0.000 description 1
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
• 208000017787 Paraneoplastic neurologic syndrome Diseases 0.000 description 1
• 229910002666 PdCl2 Inorganic materials 0.000 description 1
• 102100027913 Peptidyl-prolyl cis-trans isomerase FKBP1A Human genes 0.000 description 1
• 102000003992 Peroxidases Human genes 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
• 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 1
• 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 1
• 208000007913 Pituitary Neoplasms Diseases 0.000 description 1
• 102100035194 Placenta growth factor Human genes 0.000 description 1
• 102000011653 Platelet-Derived Growth Factor Receptors Human genes 0.000 description 1
• 241000288906 Primates Species 0.000 description 1
• 239000004146 Propane-1,2-diol Substances 0.000 description 1
• 102000006478 Protein Phosphatase 2 Human genes 0.000 description 1
• 108010058956 Protein Phosphatase 2 Proteins 0.000 description 1
• 102100037787 Protein-tyrosine kinase 2-beta Human genes 0.000 description 1
• 201000004681 Psoriasis Diseases 0.000 description 1
• 102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 description 1
• 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 1
• 102100033536 Ribosomal protein S6 kinase alpha-1 Human genes 0.000 description 1
• 241000283984 Rodentia Species 0.000 description 1
• 101700032040 SMAD1 Proteins 0.000 description 1
• 206010039710 Scleroderma Diseases 0.000 description 1
• 229940124639 Selective inhibitor Drugs 0.000 description 1
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
• 108010071390 Serum Albumin Proteins 0.000 description 1
• 102000007562 Serum Albumin Human genes 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• 238000006161 Suzuki-Miyaura coupling reaction Methods 0.000 description 1
• 201000009594 Systemic Scleroderma Diseases 0.000 description 1
• 206010042953 Systemic sclerosis Diseases 0.000 description 1
• 210000001744 T-lymphocyte Anatomy 0.000 description 1
• 101150109894 TGFA gene Proteins 0.000 description 1
• 108010006877 Tacrolimus Binding Protein 1A Proteins 0.000 description 1
• 241001582429 Tetracis Species 0.000 description 1
• BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 1
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
• 239000004473 Threonine Substances 0.000 description 1
• 208000024770 Thyroid neoplasm Diseases 0.000 description 1
• ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
• XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
• 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 1
• 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 1
• 238000005411 Van der Waals force Methods 0.000 description 1
• 208000032594 Vascular Remodeling Diseases 0.000 description 1
• 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 1
• 102100033179 Vascular endothelial growth factor receptor 3 Human genes 0.000 description 1
• 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• HONJPVLFWAUOFB-UHFFFAOYSA-N [2-(2,5-difluorophenyl)-1,8-naphthyridin-4-yl]boronic acid Chemical compound N=1C2=NC=CC=C2C(B(O)O)=CC=1C1=CC(F)=CC=C1F HONJPVLFWAUOFB-UHFFFAOYSA-N 0.000 description 1
• LHAGKQJCMHVRHE-UHFFFAOYSA-N [2-(2-cyanophenyl)-1,8-naphthyridin-4-yl]boronic acid Chemical compound N=1C2=NC=CC=C2C(B(O)O)=CC=1C1=CC=CC=C1C#N LHAGKQJCMHVRHE-UHFFFAOYSA-N 0.000 description 1
• IYORWNQEQQSNAD-UHFFFAOYSA-N [2-(2-fluorophenyl)-1,8-naphthyridin-4-yl]boronic acid Chemical compound N=1C2=NC=CC=C2C(B(O)O)=CC=1C1=CC=CC=C1F IYORWNQEQQSNAD-UHFFFAOYSA-N 0.000 description 1
• SUCLGFZGFMPAQC-UHFFFAOYSA-N [2-(6-methylpyridin-2-yl)-1,8-naphthyridin-4-yl]boronic acid Chemical compound CC1=CC=CC(C=2N=C3N=CC=CC3=C(B(O)O)C=2)=N1 SUCLGFZGFMPAQC-UHFFFAOYSA-N 0.000 description 1
• SFFUUZYGOWWFTD-UHFFFAOYSA-N [2-[2-fluoro-5-(trifluoromethyl)phenyl]-1,8-naphthyridin-4-yl]boronic acid Chemical compound N=1C2=NC=CC=C2C(B(O)O)=CC=1C1=CC(C(F)(F)F)=CC=C1F SFFUUZYGOWWFTD-UHFFFAOYSA-N 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• SPEUIVXLLWOEMJ-UHFFFAOYSA-N acetaldehyde dimethyl acetal Natural products COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 1
• IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
• 238000006640 acetylation reaction Methods 0.000 description 1
• 238000005903 acid hydrolysis reaction Methods 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
• 230000003213 activating effect Effects 0.000 description 1
• 239000012042 active reagent Substances 0.000 description 1
• 125000002252 acyl group Chemical group 0.000 description 1
• 208000009956 adenocarcinoma Diseases 0.000 description 1
• 230000001464 adherent effect Effects 0.000 description 1
• WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 238000006136 alcoholysis reaction Methods 0.000 description 1
• 229940072056 alginate Drugs 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 125000002723 alicyclic group Chemical group 0.000 description 1
• 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
• 125000003545 alkoxy group Chemical group 0.000 description 1
• 125000005907 alkyl ester group Chemical group 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• AEMOLEFTQBMNLQ-BKBMJHBISA-N alpha-D-galacturonic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-BKBMJHBISA-N 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
• AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
• ILRRQNADMUWWFW-UHFFFAOYSA-K aluminium phosphate Chemical compound O1[Al]2OP1(=O)O2 ILRRQNADMUWWFW-UHFFFAOYSA-K 0.000 description 1
• 238000010640 amide synthesis reaction Methods 0.000 description 1
• 230000003698 anagen phase Effects 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• 230000019552 anatomical structure morphogenesis Effects 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
• 230000003527 anti-angiogenesis Effects 0.000 description 1
• 230000001093 anti-cancer Effects 0.000 description 1
• 230000003510 anti-fibrotic effect Effects 0.000 description 1
• 230000003110 anti-inflammatory effect Effects 0.000 description 1
• 239000000427 antigen Substances 0.000 description 1
• 108091007433 antigens Proteins 0.000 description 1
• 102000036639 antigens Human genes 0.000 description 1
• 150000001491 aromatic compounds Chemical class 0.000 description 1
• 150000001543 aryl boronic acids Chemical class 0.000 description 1
• 150000001500 aryl chlorides Chemical class 0.000 description 1
• 229940072107 ascorbate Drugs 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 229940009098 aspartate Drugs 0.000 description 1
• 210000001130 astrocyte Anatomy 0.000 description 1
• 230000003305 autocrine Effects 0.000 description 1
• 230000035578 autophosphorylation Effects 0.000 description 1
• 239000000022 bacteriostatic agent Substances 0.000 description 1
• 230000006399 behavior Effects 0.000 description 1
• 229960000686 benzalkonium chloride Drugs 0.000 description 1
• 235000019445 benzyl alcohol Nutrition 0.000 description 1
• 150000003938 benzyl alcohols Chemical class 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
• XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
• 125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 239000012867 bioactive agent Substances 0.000 description 1
• 229920002988 biodegradable polymer Polymers 0.000 description 1
• 239000004621 biodegradable polymer Substances 0.000 description 1
• 230000008512 biological response Effects 0.000 description 1
• 238000001574 biopsy Methods 0.000 description 1
• SUAVNZMIOODRBR-UHFFFAOYSA-N bis(trifluoromethylsulfonyloxy)boranyl trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OB(OS(=O)(=O)C(F)(F)F)OS(=O)(=O)C(F)(F)F SUAVNZMIOODRBR-UHFFFAOYSA-N 0.000 description 1
• 210000000601 blood cell Anatomy 0.000 description 1
• 229910052796 boron Inorganic materials 0.000 description 1
• 150000001642 boronic acid derivatives Chemical class 0.000 description 1
• 125000005620 boronic acid group Chemical class 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 210000000133 brain stem Anatomy 0.000 description 1
• 210000000481 breast Anatomy 0.000 description 1
• 125000005997 bromomethyl group Chemical group 0.000 description 1
• 210000000621 bronchi Anatomy 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 210000004899 c-terminal region Anatomy 0.000 description 1
• MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
• 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
• 235000013877 carbamide Nutrition 0.000 description 1
• 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
• 235000014633 carbohydrates Nutrition 0.000 description 1
• 150000001720 carbohydrates Chemical class 0.000 description 1
• 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 150000001735 carboxylic acids Chemical class 0.000 description 1
• 230000000747 cardiac effect Effects 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 230000022131 cell cycle Effects 0.000 description 1
• 230000006369 cell cycle progression Effects 0.000 description 1
• 230000005779 cell damage Effects 0.000 description 1
• 208000037887 cell injury Diseases 0.000 description 1
• 230000004709 cell invasion Effects 0.000 description 1
• 230000009087 cell motility Effects 0.000 description 1
• 210000003855 cell nucleus Anatomy 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• 239000002738 chelating agent Substances 0.000 description 1
• 150000005829 chemical entities Chemical class 0.000 description 1
• 238000007385 chemical modification Methods 0.000 description 1
• 238000002512 chemotherapy Methods 0.000 description 1
• 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
• KVSASDOGYIBWTA-UHFFFAOYSA-N chloro benzoate Chemical compound ClOC(=O)C1=CC=CC=C1 KVSASDOGYIBWTA-UHFFFAOYSA-N 0.000 description 1
• 230000001684 chronic effect Effects 0.000 description 1
• 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
• 229940001468 citrate Drugs 0.000 description 1
• 238000003776 cleavage reaction Methods 0.000 description 1
• 238000010367 cloning Methods 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 208000028831 congenital heart disease Diseases 0.000 description 1
• 208000018631 connective tissue disease Diseases 0.000 description 1
• 239000000470 constituent Substances 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 239000012043 crude product Substances 0.000 description 1
• 238000003235 crystal violet staining Methods 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 210000004748 cultured cell Anatomy 0.000 description 1
• 238000011461 current therapy Methods 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 231100000433 cytotoxic Toxicity 0.000 description 1
• 230000001472 cytotoxic effect Effects 0.000 description 1
• 238000006114 decarboxylation reaction Methods 0.000 description 1
• 230000007423 decrease Effects 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 230000007547 defect Effects 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• 230000018044 dehydration Effects 0.000 description 1
• 238000006297 dehydration reaction Methods 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 230000030609 dephosphorylation Effects 0.000 description 1
• 238000006209 dephosphorylation reaction Methods 0.000 description 1
• 230000002074 deregulated effect Effects 0.000 description 1
• 238000001212 derivatisation Methods 0.000 description 1
• 210000004207 dermis Anatomy 0.000 description 1
• 230000001687 destabilization Effects 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• 206010012601 diabetes mellitus Diseases 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
• 150000004683 dihydrates Chemical class 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
• 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• 230000003292 diminished effect Effects 0.000 description 1
• 229910000397 disodium phosphate Inorganic materials 0.000 description 1
• PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 1
• MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
• 229940043264 dodecyl sulfate Drugs 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 230000003828 downregulation Effects 0.000 description 1
• 238000009510 drug design Methods 0.000 description 1
• 238000009509 drug development Methods 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 230000012202 endocytosis Effects 0.000 description 1
• 210000004696 endometrium Anatomy 0.000 description 1
• 230000003511 endothelial effect Effects 0.000 description 1
• 102000012803 ephrin Human genes 0.000 description 1
• 108060002566 ephrin Proteins 0.000 description 1
• 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
• 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
• 210000003238 esophagus Anatomy 0.000 description 1
• 230000032050 esterification Effects 0.000 description 1
• 238000005886 esterification reaction Methods 0.000 description 1
• 150000002170 ethers Chemical class 0.000 description 1
• LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 210000002744 extracellular matrix Anatomy 0.000 description 1
• 208000030533 eye disease Diseases 0.000 description 1
• 239000003889 eye drop Substances 0.000 description 1
• 229940012356 eye drops Drugs 0.000 description 1
• 230000002349 favourable effect Effects 0.000 description 1
• 239000012091 fetal bovine serum Substances 0.000 description 1
• 210000002950 fibroblast Anatomy 0.000 description 1
• 230000000893 fibroproliferative effect Effects 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 238000001914 filtration Methods 0.000 description 1
• 239000012467 final product Substances 0.000 description 1
• 238000003818 flash chromatography Methods 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 235000019634 flavors Nutrition 0.000 description 1
• 238000002866 fluorescence resonance energy transfer Methods 0.000 description 1
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
• 235000013305 food Nutrition 0.000 description 1
• 239000008098 formaldehyde solution Substances 0.000 description 1
• DSLZVSRJTYRBFB-DUHBMQHGSA-N galactaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O DSLZVSRJTYRBFB-DUHBMQHGSA-N 0.000 description 1
• 229940044627 gamma-interferon Drugs 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 230000007045 gastrulation Effects 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 231100000118 genetic alteration Toxicity 0.000 description 1
• 230000004077 genetic alteration Effects 0.000 description 1
• 230000009395 genetic defect Effects 0.000 description 1
• 239000011521 glass Substances 0.000 description 1
• 208000005017 glioblastoma Diseases 0.000 description 1
• 229940050410 gluconate Drugs 0.000 description 1
• 229930195712 glutamate Natural products 0.000 description 1
• 235000013773 glyceryl triacetate Nutrition 0.000 description 1
• 150000004795 grignard reagents Chemical class 0.000 description 1
• 230000031774 hair cycle Effects 0.000 description 1
• 125000001188 haloalkyl group Chemical group 0.000 description 1
• 125000005843 halogen group Chemical group 0.000 description 1
• 210000003128 head Anatomy 0.000 description 1
• 230000035876 healing Effects 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 230000003862 health status Effects 0.000 description 1
• 210000002216 heart Anatomy 0.000 description 1
• 210000003494 hepatocyte Anatomy 0.000 description 1
• MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
• FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
• 125000006038 hexenyl group Chemical group 0.000 description 1
• 125000005980 hexynyl group Chemical group 0.000 description 1
• 230000013632 homeostatic process Effects 0.000 description 1
• 150000002430 hydrocarbons Chemical class 0.000 description 1
• 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• 230000002209 hydrophobic effect Effects 0.000 description 1
• 125000002887 hydroxy group Chemical class [H]O* 0.000 description 1
• WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
• 230000001969 hypertrophic effect Effects 0.000 description 1
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
• 125000002632 imidazolidinyl group Chemical group 0.000 description 1
• 125000004857 imidazopyridinyl group Chemical class N1C(=NC2=C1C=CC=N2)* 0.000 description 1
• 210000002865 immune cell Anatomy 0.000 description 1
• 208000026278 immune system disease Diseases 0.000 description 1
• 238000009169 immunotherapy Methods 0.000 description 1
• 238000000099 in vitro assay Methods 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 239000012678 infectious agent Substances 0.000 description 1
• 230000008595 infiltration Effects 0.000 description 1
• 238000001764 infiltration Methods 0.000 description 1
• 230000015788 innate immune response Effects 0.000 description 1
• 238000011081 inoculation Methods 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 210000000936 intestine Anatomy 0.000 description 1
• 230000031146 intracellular signal transduction Effects 0.000 description 1
• 230000004068 intracellular signaling Effects 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 238000011835 investigation Methods 0.000 description 1
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 108010047623 iridine Proteins 0.000 description 1
• KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
• 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 210000002510 keratinocyte Anatomy 0.000 description 1
• 230000029411 keratinocyte apoptotic process Effects 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 208000017169 kidney disease Diseases 0.000 description 1
• 238000000021 kinase assay Methods 0.000 description 1
• 229940001447 lactate Drugs 0.000 description 1
• 229940099584 lactobionate Drugs 0.000 description 1
• JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
• 210000000867 larynx Anatomy 0.000 description 1
• 231100000518 lethal Toxicity 0.000 description 1
• 230000001665 lethal effect Effects 0.000 description 1
• 208000032839 leukemia Diseases 0.000 description 1
• 108020001756 ligand binding domains Proteins 0.000 description 1
• 208000019423 liver disease Diseases 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 230000004199 lung function Effects 0.000 description 1
• 230000035168 lymphangiogenesis Effects 0.000 description 1
• 210000004324 lymphatic system Anatomy 0.000 description 1
• 210000001365 lymphatic vessel Anatomy 0.000 description 1
• 239000006166 lysate Substances 0.000 description 1
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
• 210000002540 macrophage Anatomy 0.000 description 1
• 108010053292 macrophage stimulating protein Proteins 0.000 description 1
• 208000002780 macular degeneration Diseases 0.000 description 1
• 229910001629 magnesium chloride Inorganic materials 0.000 description 1
• FODOUIXGKGNSMR-UHFFFAOYSA-L magnesium;2-oxidooxycarbonylbenzoate;hexahydrate Chemical compound O.O.O.O.O.O.[Mg+2].[O-]OC(=O)C1=CC=CC=C1C([O-])=O FODOUIXGKGNSMR-UHFFFAOYSA-L 0.000 description 1
• 230000014759 maintenance of location Effects 0.000 description 1
• 229940049920 malate Drugs 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
• 150000002690 malonic acid derivatives Chemical class 0.000 description 1
• 210000005075 mammary gland Anatomy 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
• 239000011565 manganese chloride Substances 0.000 description 1
• 235000002867 manganese chloride Nutrition 0.000 description 1
• 230000035800 maturation Effects 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 229940127554 medical product Drugs 0.000 description 1
• 230000007721 medicinal effect Effects 0.000 description 1
• 210000003716 mesoderm Anatomy 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 229910044991 metal oxide Inorganic materials 0.000 description 1
• 150000004706 metal oxides Chemical class 0.000 description 1
• 150000002739 metals Chemical class 0.000 description 1
• 125000005341 metaphosphate group Chemical group 0.000 description 1
• 230000001394 metastastic effect Effects 0.000 description 1
• 230000008883 metastatic behaviour Effects 0.000 description 1
• 206010061289 metastatic neoplasm Diseases 0.000 description 1
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
• MGIYCRUAYQQSNL-UHFFFAOYSA-N methyl 2-bromo-4-methoxybenzoate Chemical compound COC(=O)C1=CC=C(OC)C=C1Br MGIYCRUAYQQSNL-UHFFFAOYSA-N 0.000 description 1
• 229940095102 methyl benzoate Drugs 0.000 description 1
• 210000000274 microglia Anatomy 0.000 description 1
• 230000001617 migratory effect Effects 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 230000009456 molecular mechanism Effects 0.000 description 1
• 150000004682 monohydrates Chemical class 0.000 description 1
• 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
• 235000019799 monosodium phosphate Nutrition 0.000 description 1
• 210000005012 myelin Anatomy 0.000 description 1
• 208000031225 myocardial ischemia Diseases 0.000 description 1
• GIOSUODMPCUDON-UHFFFAOYSA-N n-(3-acetylpyridin-2-yl)-6-methylpyridine-2-carboxamide Chemical compound CC(=O)C1=CC=CN=C1NC(=O)C1=CC=CC(C)=N1 GIOSUODMPCUDON-UHFFFAOYSA-N 0.000 description 1
• YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
• 210000003739 neck Anatomy 0.000 description 1
• 239000013642 negative control Substances 0.000 description 1
• 230000014399 negative regulation of angiogenesis Effects 0.000 description 1
• 230000000926 neurological effect Effects 0.000 description 1
• 150000002825 nitriles Chemical class 0.000 description 1
• 150000002828 nitro derivatives Chemical class 0.000 description 1
• LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 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
• WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 229940049964 oleate Drugs 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 238000006384 oligomerization reaction Methods 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 230000005305 organ development Effects 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000002894 organic compounds Chemical class 0.000 description 1
• 150000001282 organosilanes Chemical class 0.000 description 1
• 125000001190 organyl group Chemical group 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
• 229910052763 palladium Inorganic materials 0.000 description 1
• PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
• 201000002528 pancreatic cancer Diseases 0.000 description 1
• 208000008443 pancreatic carcinoma Diseases 0.000 description 1
• 244000052769 pathogen Species 0.000 description 1
• 230000001717 pathogenic effect Effects 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
• 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000005981 pentynyl group Chemical group 0.000 description 1
• 210000003668 pericyte Anatomy 0.000 description 1
• 230000002093 peripheral effect Effects 0.000 description 1
• 210000001428 peripheral nervous system Anatomy 0.000 description 1
• 210000004303 peritoneum Anatomy 0.000 description 1
• 108040007629 peroxidase activity proteins Proteins 0.000 description 1
• JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
• 235000019271 petrolatum Nutrition 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 230000003285 pharmacodynamic effect Effects 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 210000003800 pharynx Anatomy 0.000 description 1
• 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
• 150000002989 phenols Chemical class 0.000 description 1
• 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
• 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
• 229940049953 phenylacetate Drugs 0.000 description 1
• WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
• UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
• XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
• 238000000053 physical method Methods 0.000 description 1
• 210000002826 placenta Anatomy 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 229920005862 polyol Polymers 0.000 description 1
• 150000003077 polyols Chemical class 0.000 description 1
• 229920000137 polyphosphoric acid Polymers 0.000 description 1
• 239000013641 positive control Substances 0.000 description 1
• 230000002980 postoperative effect Effects 0.000 description 1
• 229910000027 potassium carbonate Inorganic materials 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 238000002953 preparative HPLC Methods 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 230000007112 pro inflammatory response Effects 0.000 description 1
• 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
• QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
• 229960004063 propylene glycol Drugs 0.000 description 1
• 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
• 230000009822 protein phosphorylation Effects 0.000 description 1
• 230000017854 proteolysis Effects 0.000 description 1
• 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
• 230000002685 pulmonary effect Effects 0.000 description 1
• 208000005069 pulmonary fibrosis Diseases 0.000 description 1
• 238000005086 pumping Methods 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical group OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
• 150000003230 pyrimidines Chemical class 0.000 description 1
• 150000005255 pyrrolopyridines Chemical class 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• 230000035484 reaction time Effects 0.000 description 1
• 239000012048 reactive intermediate Substances 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 210000000664 rectum Anatomy 0.000 description 1
• 230000003014 reinforcing effect Effects 0.000 description 1
• 238000007634 remodeling Methods 0.000 description 1
• 201000002793 renal fibrosis Diseases 0.000 description 1
• 230000010076 replication Effects 0.000 description 1
• 230000028617 response to DNA damage stimulus Effects 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
• 229960001860 salicylate Drugs 0.000 description 1
• 229930182490 saponin Natural products 0.000 description 1
• 150000007949 saponins Chemical class 0.000 description 1
• 235000017709 saponins Nutrition 0.000 description 1
• 230000036573 scar formation Effects 0.000 description 1
• 238000002821 scintillation proximity assay Methods 0.000 description 1
• 230000007017 scission Effects 0.000 description 1
• 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 230000028327 secretion Effects 0.000 description 1
• 238000013207 serial dilution Methods 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 239000000377 silicon dioxide Substances 0.000 description 1
• 210000001626 skin fibroblast Anatomy 0.000 description 1
• 208000000587 small cell lung carcinoma Diseases 0.000 description 1
• 150000003384 small molecules Chemical class 0.000 description 1
• 210000002460 smooth muscle Anatomy 0.000 description 1
• 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
• AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
• 229910000162 sodium phosphate Inorganic materials 0.000 description 1
• 239000008347 soybean phospholipid Substances 0.000 description 1
• 125000003003 spiro group Chemical group 0.000 description 1
• 238000005507 spraying Methods 0.000 description 1
• 229940031439 squalene Drugs 0.000 description 1
• TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
• 206010041823 squamous cell carcinoma Diseases 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 210000002536 stromal cell Anatomy 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 229940086735 succinate Drugs 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 150000003462 sulfoxides Chemical class 0.000 description 1
• 230000010741 sumoylation Effects 0.000 description 1
• 238000001356 surgical procedure Methods 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 239000003826 tablet Substances 0.000 description 1
• 238000002626 targeted therapy Methods 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• 230000002123 temporal effect Effects 0.000 description 1
• 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 238000010998 test method Methods 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
• 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
• 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 125000001984 thiazolidinyl group Chemical group 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 229940125670 thienopyridine Drugs 0.000 description 1
• 239000002175 thienopyridine Substances 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 210000001685 thyroid gland Anatomy 0.000 description 1
• 238000002877 time resolved fluorescence resonance energy transfer Methods 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• 230000009261 transgenic effect Effects 0.000 description 1
• 238000011830 transgenic mouse model Methods 0.000 description 1
• 230000032258 transport Effects 0.000 description 1
• 229960002622 triacetin Drugs 0.000 description 1
• USKQYZHWJZDNCM-UHFFFAOYSA-N tributyl-(6-methylpyridin-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CC(C)=N1 USKQYZHWJZDNCM-UHFFFAOYSA-N 0.000 description 1
• JDLDTRXYGQMDRV-UHFFFAOYSA-N tricesium;borate Chemical compound [Cs+].[Cs+].[Cs+].[O-]B([O-])[O-] JDLDTRXYGQMDRV-UHFFFAOYSA-N 0.000 description 1
• FWSPXZXVNVQHIF-UHFFFAOYSA-N triethyl(ethynyl)silane Chemical group CC[Si](CC)(CC)C#C FWSPXZXVNVQHIF-UHFFFAOYSA-N 0.000 description 1
• VHKIEYIESYMHPT-UHFFFAOYSA-N triethyl(methoxycarbonylsulfamoyl)azanium;hydroxide Chemical compound [OH-].CC[N+](CC)(CC)S(=O)(=O)NC(=O)OC VHKIEYIESYMHPT-UHFFFAOYSA-N 0.000 description 1
• 150000008648 triflates Chemical class 0.000 description 1
• PBIMIGNDTBRRPI-UHFFFAOYSA-N trifluoro borate Chemical compound FOB(OF)OF PBIMIGNDTBRRPI-UHFFFAOYSA-N 0.000 description 1
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
• JUDXOKKZTISQDJ-UHFFFAOYSA-N triphenylphosphane;hydrochloride Chemical compound Cl.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 JUDXOKKZTISQDJ-UHFFFAOYSA-N 0.000 description 1
• 210000004881 tumor cell Anatomy 0.000 description 1
• 239000000717 tumor promoter Substances 0.000 description 1
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
• 238000010798 ubiquitination Methods 0.000 description 1
• 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
• 150000003672 ureas Chemical class 0.000 description 1
• 230000007556 vascular defect Effects 0.000 description 1
• 230000006459 vascular development Effects 0.000 description 1
• 210000005166 vasculature Anatomy 0.000 description 1
• 230000004862 vasculogenesis Effects 0.000 description 1
• 229940099259 vaseline Drugs 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 229920002554 vinyl polymer Polymers 0.000 description 1
• 230000003612 virological effect Effects 0.000 description 1
• 210000001835 viscera Anatomy 0.000 description 1
• 239000011782 vitamin Substances 0.000 description 1
• 235000013343 vitamin Nutrition 0.000 description 1
• 229940088594 vitamin Drugs 0.000 description 1
• 229930003231 vitamin Natural products 0.000 description 1
• 239000008215 water for injection Substances 0.000 description 1
• 238000005303 weighing Methods 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 239000008096 xylene Substances 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1
• 150000003752 zinc compounds Chemical class 0.000 description 1