UA71971C2 - Diaminothiazoles, composition based thereon, a method for modulation of protein kinases activity, a method for the treatment of diseases mediated by protein kinases - Google Patents

Info

Publication number

UA71971C2

UA71971C2 UA2001129215A UA2001129215A UA71971C2 UA 71971 C2 UA71971 C2 UA 71971C2 UA 2001129215 A UA2001129215 A UA 2001129215A UA 2001129215 A UA2001129215 A UA 2001129215A UA 71971 C2 UA71971 C2 UA 71971C2

Authority

UA

Ukraine

Prior art keywords

amino

aryl

heteroaryl

formula

substituted

Prior art date

1999-06-04

Links

• Espacenet
• Global Dossier
• Discuss

• 238000000034 method Methods 0.000 title claims abstract description 52
• 230000000694 effects Effects 0.000 title claims abstract description 48
• 102000001253 Protein Kinase Human genes 0.000 title claims abstract description 37
• 108060006633 protein kinase Proteins 0.000 title claims abstract description 37
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 23
• 201000010099 disease Diseases 0.000 title claims abstract description 22
• 230000001404 mediated effect Effects 0.000 title claims description 10
• WKXCZMFWXZRMEZ-UHFFFAOYSA-N 1,3-thiazole-2,4-diamine Chemical class NC1=CSC(N)=N1 WKXCZMFWXZRMEZ-UHFFFAOYSA-N 0.000 title abstract description 3
• 239000000203 mixture Substances 0.000 title description 46
• 150000001875 compounds Chemical class 0.000 claims abstract description 202
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 29
• 230000033115 angiogenesis Effects 0.000 claims abstract description 18
• 230000004663 cell proliferation Effects 0.000 claims abstract description 17
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 17
• 125000003118 aryl group Chemical group 0.000 claims description 97
• 125000000217 alkyl group Chemical group 0.000 claims description 80
• 125000001072 heteroaryl group Chemical group 0.000 claims description 76
• 229910052739 hydrogen Inorganic materials 0.000 claims description 48
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 43
• 239000001257 hydrogen Substances 0.000 claims description 43
• 150000003839 salts Chemical class 0.000 claims description 43
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 40
• 150000002431 hydrogen Chemical group 0.000 claims description 29
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 29
• 125000003545 alkoxy group Chemical group 0.000 claims description 25
• 239000002207 metabolite Substances 0.000 claims description 23
• 108091000080 Phosphotransferase Proteins 0.000 claims description 22
• 102000020233 phosphotransferase Human genes 0.000 claims description 22
• 239000000651 prodrug Substances 0.000 claims description 22
• 229940002612 prodrug Drugs 0.000 claims description 22
• 125000003342 alkenyl group Chemical group 0.000 claims description 14
• 238000011161 development Methods 0.000 claims description 14
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
• 125000005843 halogen group Chemical group 0.000 claims description 11
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
• 241000124008 Mammalia Species 0.000 claims description 8
• 239000003937 drug carrier Substances 0.000 claims description 7
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
• 229910052731 fluorine Inorganic materials 0.000 claims description 6
• 125000004104 aryloxy group Chemical group 0.000 claims description 5
• 239000000460 chlorine Substances 0.000 claims description 5
• 239000011737 fluorine Substances 0.000 claims description 5
• 229910052760 oxygen Inorganic materials 0.000 claims description 5
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
• 125000003282 alkyl amino group Chemical group 0.000 claims description 4
• 229910052801 chlorine Inorganic materials 0.000 claims description 4
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
• 125000003277 amino group Chemical group 0.000 claims description 3
• 239000003085 diluting agent Substances 0.000 claims description 3
• 125000004442 acylamino group Chemical group 0.000 claims description 2
• 125000006574 non-aromatic ring group Chemical group 0.000 claims description 2
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 3
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 2
• 125000006413 ring segment Chemical group 0.000 claims 1
• 238000012876 topography Methods 0.000 claims 1
• 201000011510 cancer Diseases 0.000 abstract description 26
• 230000001225 therapeutic effect Effects 0.000 abstract description 10
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 abstract description 7
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 abstract description 7
• 230000019491 signal transduction Effects 0.000 abstract description 5
• 201000004681 Psoriasis Diseases 0.000 abstract description 4
• 206010039073 rheumatoid arthritis Diseases 0.000 abstract description 4
• 206010012689 Diabetic retinopathy Diseases 0.000 abstract description 2
• 208000010412 Glaucoma Diseases 0.000 abstract description 2
• 201000003142 neovascular glaucoma Diseases 0.000 abstract description 2
• 230000000069 prophylactic effect Effects 0.000 abstract description 2
• 238000002474 experimental method Methods 0.000 description 189
• 238000005481 NMR spectroscopy Methods 0.000 description 144
• 239000000243 solution Substances 0.000 description 89
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 80
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 67
• 239000011572 manganese Substances 0.000 description 64
• 210000004027 cell Anatomy 0.000 description 54
• -1 SOC1/Cyclin O1 Chemical class 0.000 description 50
• 239000002904 solvent Substances 0.000 description 43
• 238000006243 chemical reaction Methods 0.000 description 37
• 239000003795 chemical substances by application Substances 0.000 description 35
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 31
• 235000019439 ethyl acetate Nutrition 0.000 description 30
• 238000005160 1H NMR spectroscopy Methods 0.000 description 29
• 238000012360 testing method Methods 0.000 description 28
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
• 239000011734 sodium Substances 0.000 description 26
• 229910001868 water Inorganic materials 0.000 description 26
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
• 239000011541 reaction mixture Substances 0.000 description 23
• CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Substances CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 22
• 238000004458 analytical method Methods 0.000 description 22
• 230000005764 inhibitory process Effects 0.000 description 21
• 239000007787 solid Substances 0.000 description 20
• GRCMZHNTKLXDAP-UHFFFAOYSA-N COC1=C(OC)C(OC)=CC(C2(N)SC=C(N)N2)=C1 Chemical compound COC1=C(OC)C(OC)=CC(C2(N)SC=C(N)N2)=C1 GRCMZHNTKLXDAP-UHFFFAOYSA-N 0.000 description 19
• 239000002585 base Substances 0.000 description 19
• 239000002253 acid Substances 0.000 description 17
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
• 239000012267 brine Substances 0.000 description 16
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
• 239000003112 inhibitor Substances 0.000 description 15
• 239000000843 powder Substances 0.000 description 15
• 108090000623 proteins and genes Proteins 0.000 description 15
• 238000000354 decomposition reaction Methods 0.000 description 14
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 14
• ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 13
• ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 13
• 230000022131 cell cycle Effects 0.000 description 13
• 230000018109 developmental process Effects 0.000 description 13
• 239000012071 phase Substances 0.000 description 13
• 102000016736 Cyclin Human genes 0.000 description 12
• 108050006400 Cyclin Proteins 0.000 description 12
• 208000026478 essential tremor 5 Diseases 0.000 description 12
• 208000036719 hereditary essential 5 tremor Diseases 0.000 description 12
• VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
• 102000004169 proteins and genes Human genes 0.000 description 12
• 238000000746 purification Methods 0.000 description 12
• 238000011160 research Methods 0.000 description 12
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
• 230000015572 biosynthetic process Effects 0.000 description 11
• 239000000969 carrier Substances 0.000 description 11
• 238000004587 chromatography analysis Methods 0.000 description 11
• 239000007788 liquid Substances 0.000 description 11
• 239000002609 medium Substances 0.000 description 11
• 235000018102 proteins Nutrition 0.000 description 11
• 239000007858 starting material Substances 0.000 description 11
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
• 238000003556 assay Methods 0.000 description 10
• 229910052748 manganese Inorganic materials 0.000 description 10
• 239000003921 oil Substances 0.000 description 10
• 235000019198 oils Nutrition 0.000 description 10
• 230000008569 process Effects 0.000 description 10
• 102000005962 receptors Human genes 0.000 description 10
• 108020003175 receptors Proteins 0.000 description 10
• 239000000741 silica gel Substances 0.000 description 10
• 229910002027 silica gel Inorganic materials 0.000 description 10
• 238000004809 thin layer chromatography Methods 0.000 description 10
• 102000004190 Enzymes Human genes 0.000 description 9
• 108090000790 Enzymes Proteins 0.000 description 9
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 9
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
• 238000001914 filtration Methods 0.000 description 9
• 230000002829 reductive effect Effects 0.000 description 9
• 238000003756 stirring Methods 0.000 description 9
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
• 150000001412 amines Chemical class 0.000 description 8
• 239000007864 aqueous solution Substances 0.000 description 8
• 125000004432 carbon atom Chemical group C* 0.000 description 8
• 230000003197 catalytic effect Effects 0.000 description 8
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Natural products OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 8
• 239000003814 drug Substances 0.000 description 8
• 238000002347 injection Methods 0.000 description 8
• 239000007924 injection Substances 0.000 description 8
• 210000001525 retina Anatomy 0.000 description 8
• 239000000758 substrate Substances 0.000 description 8
• 239000000725 suspension Substances 0.000 description 8
• AGJBKFAPBKOEGA-UHFFFAOYSA-M 2-methoxyethylmercury(1+);acetate Chemical compound COCC[Hg]OC(C)=O AGJBKFAPBKOEGA-UHFFFAOYSA-M 0.000 description 7
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
• 230000009471 action Effects 0.000 description 7
• 229910052799 carbon Inorganic materials 0.000 description 7
• VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 7
• 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 7
• 239000012044 organic layer Substances 0.000 description 7
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
• 239000000047 product Substances 0.000 description 7
• 230000035755 proliferation Effects 0.000 description 7
• 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 6
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
• XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 6
• 102000002554 Cyclin A Human genes 0.000 description 6
• 108010068192 Cyclin A Proteins 0.000 description 6
• 230000005778 DNA damage Effects 0.000 description 6
• 231100000277 DNA damage Toxicity 0.000 description 6
• 241000700159 Rattus Species 0.000 description 6
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
• 235000001014 amino acid Nutrition 0.000 description 6
• 150000001413 amino acids Chemical class 0.000 description 6
• 230000033228 biological regulation Effects 0.000 description 6
• 229910052796 boron Inorganic materials 0.000 description 6
• 239000002775 capsule Substances 0.000 description 6
• 229940079593 drug Drugs 0.000 description 6
• 230000006870 function Effects 0.000 description 6
• 239000003102 growth factor Substances 0.000 description 6
• 238000010438 heat treatment Methods 0.000 description 6
• 239000010410 layer Substances 0.000 description 6
• 229920001223 polyethylene glycol Polymers 0.000 description 6
• 239000002244 precipitate Substances 0.000 description 6
• 108090000765 processed proteins & peptides Proteins 0.000 description 6
• 230000001105 regulatory effect Effects 0.000 description 6
• 229920006395 saturated elastomer Polymers 0.000 description 6
• 241000701447 unidentified baculovirus Species 0.000 description 6
• 239000005711 Benzoic acid Substances 0.000 description 5
• 108091007914 CDKs Proteins 0.000 description 5
• 102000003903 Cyclin-dependent kinases Human genes 0.000 description 5
• 108090000266 Cyclin-dependent kinases Proteins 0.000 description 5
• 108010010803 Gelatin Proteins 0.000 description 5
• 241000238631 Hexapoda Species 0.000 description 5
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 5
• 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 5
• 239000002202 Polyethylene glycol Substances 0.000 description 5
• 239000004480 active ingredient Substances 0.000 description 5
• 230000035578 autophosphorylation Effects 0.000 description 5
• 239000003153 chemical reaction reagent Substances 0.000 description 5
• 239000008298 dragée Substances 0.000 description 5
• 239000000839 emulsion Substances 0.000 description 5
• 210000002889 endothelial cell Anatomy 0.000 description 5
• 238000009472 formulation Methods 0.000 description 5
• 239000008273 gelatin Substances 0.000 description 5
• 229920000159 gelatin Polymers 0.000 description 5
• 235000019322 gelatine Nutrition 0.000 description 5
• 235000011852 gelatine desserts Nutrition 0.000 description 5
• 239000001963 growth medium Substances 0.000 description 5
• 230000002209 hydrophobic effect Effects 0.000 description 5
• 238000002329 infrared spectrum Methods 0.000 description 5
• 230000002401 inhibitory effect Effects 0.000 description 5
• 230000003834 intracellular effect Effects 0.000 description 5
• 229910052740 iodine Inorganic materials 0.000 description 5
• 239000008101 lactose Substances 0.000 description 5
• 239000000463 material Substances 0.000 description 5
• 229910052757 nitrogen Inorganic materials 0.000 description 5
• 239000002245 particle Substances 0.000 description 5
• DTBNBXWJWCWCIK-UHFFFAOYSA-K phosphonatoenolpyruvate Chemical compound [O-]C(=O)C(=C)OP([O-])([O-])=O DTBNBXWJWCWCIK-UHFFFAOYSA-K 0.000 description 5
• 238000002360 preparation method Methods 0.000 description 5
• 210000001210 retinal vessel Anatomy 0.000 description 5
• 239000000126 substance Substances 0.000 description 5
• BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 5
• VEUMBMHMMCOFAG-UHFFFAOYSA-N 2,3-dihydrooxadiazole Chemical compound N1NC=CO1 VEUMBMHMMCOFAG-UHFFFAOYSA-N 0.000 description 4
• 102100022014 Angiopoietin-1 receptor Human genes 0.000 description 4
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
• 108010001336 Horseradish Peroxidase Proteins 0.000 description 4
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
• 241001465754 Metazoa Species 0.000 description 4
• 229920002472 Starch Polymers 0.000 description 4
• 239000013543 active substance Substances 0.000 description 4
• 125000004429 atom Chemical group 0.000 description 4
• 239000007795 chemical reaction product Substances 0.000 description 4
• 239000000975 dye Substances 0.000 description 4
• 239000003480 eluent Substances 0.000 description 4
• 150000002148 esters Chemical class 0.000 description 4
• 239000000945 filler Substances 0.000 description 4
• 239000000706 filtrate Substances 0.000 description 4
• 125000000524 functional group Chemical group 0.000 description 4
• 239000007789 gas Substances 0.000 description 4
• 239000007903 gelatin capsule Substances 0.000 description 4
• 238000007429 general method Methods 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
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
• 150000007522 mineralic acids Chemical class 0.000 description 4
• 150000007524 organic acids Chemical class 0.000 description 4
• 230000003647 oxidation Effects 0.000 description 4
• 238000007254 oxidation reaction Methods 0.000 description 4
• 229930029653 phosphoenolpyruvate Natural products 0.000 description 4
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
• 238000012545 processing Methods 0.000 description 4
• 239000003909 protein kinase inhibitor Substances 0.000 description 4
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
• 108091008598 receptor tyrosine kinases Proteins 0.000 description 4
• 102000027426 receptor tyrosine kinases Human genes 0.000 description 4
• 230000009467 reduction Effects 0.000 description 4
• 230000002441 reversible effect Effects 0.000 description 4
• 239000011780 sodium chloride Substances 0.000 description 4
• 235000000346 sugar Nutrition 0.000 description 4
• 238000003786 synthesis reaction Methods 0.000 description 4
• 210000001519 tissue Anatomy 0.000 description 4
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
• CKQHAYFOPRIUOM-UHFFFAOYSA-N 3'-Aminoacetophenone Chemical compound CC(=O)C1=CC=CC(N)=C1 CKQHAYFOPRIUOM-UHFFFAOYSA-N 0.000 description 3
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
• YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 3
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
• 101000851357 Homo sapiens Troponin T, slow skeletal muscle Proteins 0.000 description 3
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 3
• 239000004698 Polyethylene Substances 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• 108050002653 Retinoblastoma protein Proteins 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 3
• 102100036860 Troponin T, slow skeletal muscle Human genes 0.000 description 3
• 150000007513 acids Chemical class 0.000 description 3
• 230000010933 acylation Effects 0.000 description 3
• 238000005917 acylation reaction Methods 0.000 description 3
• 150000001408 amides Chemical class 0.000 description 3
• 230000002491 angiogenic effect Effects 0.000 description 3
• 229910052786 argon Inorganic materials 0.000 description 3
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
• KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 3
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
• 239000011230 binding agent Substances 0.000 description 3
• CVXBEEMKQHEXEN-UHFFFAOYSA-N carbaryl Chemical class C1=CC=C2C(OC(=O)NC)=CC=CC2=C1 CVXBEEMKQHEXEN-UHFFFAOYSA-N 0.000 description 3
• AOXOCDRNSPFDPE-UKEONUMOSA-N chembl413654 Chemical compound C([C@H](C(=O)NCC(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](C)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@@H](N)CCC(O)=O)C1=CC=C(O)C=C1 AOXOCDRNSPFDPE-UKEONUMOSA-N 0.000 description 3
• 230000006378 damage Effects 0.000 description 3
• 230000007547 defect Effects 0.000 description 3
• 238000001035 drying Methods 0.000 description 3
• 238000010828 elution Methods 0.000 description 3
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
• 238000003818 flash chromatography Methods 0.000 description 3
• 239000000499 gel Substances 0.000 description 3
• 230000014509 gene expression Effects 0.000 description 3
• 239000011521 glass Substances 0.000 description 3
• 235000011187 glycerol Nutrition 0.000 description 3
• 229910052736 halogen Inorganic materials 0.000 description 3
• 150000002367 halogens Chemical class 0.000 description 3
• 238000004128 high performance liquid chromatography Methods 0.000 description 3
• 150000007529 inorganic bases Chemical class 0.000 description 3
• 229940043355 kinase inhibitor Drugs 0.000 description 3
• 239000012528 membrane Substances 0.000 description 3
• 229910052751 metal Inorganic materials 0.000 description 3
• 239000002184 metal Substances 0.000 description 3
• 150000004702 methyl esters Chemical class 0.000 description 3
• 230000004048 modification Effects 0.000 description 3
• 238000012986 modification Methods 0.000 description 3
• 201000008048 nemaline myopathy 5 Diseases 0.000 description 3
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
• 230000003287 optical effect Effects 0.000 description 3
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Substances ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 3
• 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 3
• 239000001301 oxygen Chemical group 0.000 description 3
• NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 3
• 230000026731 phosphorylation Effects 0.000 description 3
• 238000006366 phosphorylation reaction Methods 0.000 description 3
• 239000006187 pill Substances 0.000 description 3
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
• 102000004196 processed proteins & peptides Human genes 0.000 description 3
• 230000004044 response Effects 0.000 description 3
• 238000010898 silica gel chromatography Methods 0.000 description 3
• 235000017557 sodium bicarbonate Nutrition 0.000 description 3
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
• 239000000600 sorbitol Substances 0.000 description 3
• 239000003381 stabilizer Substances 0.000 description 3
• 235000019698 starch Nutrition 0.000 description 3
• 125000001424 substituent group Chemical group 0.000 description 3
• 238000006467 substitution reaction Methods 0.000 description 3
• 150000008163 sugars Chemical class 0.000 description 3
• 230000004083 survival effect Effects 0.000 description 3
• 239000006188 syrup Substances 0.000 description 3
• 235000020357 syrup Nutrition 0.000 description 3
• 231100000419 toxicity Toxicity 0.000 description 3
• 230000001988 toxicity Effects 0.000 description 3
• 238000012546 transfer Methods 0.000 description 3
• 230000002792 vascular Effects 0.000 description 3
• 210000004127 vitreous body Anatomy 0.000 description 3
• 229910052727 yttrium Inorganic materials 0.000 description 3
• KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 2
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• REXUYBKPWIPONM-UHFFFAOYSA-N 2-bromoacetonitrile Chemical compound BrCC#N REXUYBKPWIPONM-UHFFFAOYSA-N 0.000 description 2
• IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
• LVRFTAZAXQPQHI-UHFFFAOYSA-N 2-hydroxy-4-methylvaleric acid Chemical compound CC(C)CC(O)C(O)=O LVRFTAZAXQPQHI-UHFFFAOYSA-N 0.000 description 2
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
• HSZLBBZSPHXHDJ-UHFFFAOYSA-N 4-[(4-amino-5-cyano-1,3-thiazol-2-yl)amino]benzenesulfonamide Chemical compound S1C(C#N)=C(N)N=C1NC1=CC=C(S(N)(=O)=O)C=C1 HSZLBBZSPHXHDJ-UHFFFAOYSA-N 0.000 description 2
• XPXLWEBNQPZCBC-UHFFFAOYSA-N 4-amino-2-(3,4,5-trimethoxyanilino)-1,3-thiazole-5-carbonitrile Chemical compound COC1=C(OC)C(OC)=CC(NC=2SC(=C(N)N=2)C#N)=C1 XPXLWEBNQPZCBC-UHFFFAOYSA-N 0.000 description 2
• MCNQUWLLXZZZAC-UHFFFAOYSA-N 4-cyano-1-(2,4-dichlorophenyl)-5-(4-methoxyphenyl)-n-piperidin-1-ylpyrazole-3-carboxamide Chemical compound C1=CC(OC)=CC=C1C1=C(C#N)C(C(=O)NN2CCCCC2)=NN1C1=CC=C(Cl)C=C1Cl MCNQUWLLXZZZAC-UHFFFAOYSA-N 0.000 description 2
• OMNHTTWQSSUZHO-UHFFFAOYSA-N 4-hydroxy-3,5-dimethylbenzoic acid Chemical compound CC1=CC(C(O)=O)=CC(C)=C1O OMNHTTWQSSUZHO-UHFFFAOYSA-N 0.000 description 2
• QZLSBOVWPHXCLT-UHFFFAOYSA-N 5-chlorothiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(Cl)S1 QZLSBOVWPHXCLT-UHFFFAOYSA-N 0.000 description 2
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 229920001817 Agar Polymers 0.000 description 2
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
• 102100034594 Angiopoietin-1 Human genes 0.000 description 2
• 108010048154 Angiopoietin-1 Proteins 0.000 description 2
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
• VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• 230000012746 DNA damage checkpoint Effects 0.000 description 2
• 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 2
• 102400000921 Gastrin Human genes 0.000 description 2
• 108010052343 Gastrins Proteins 0.000 description 2
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
• 235000010469 Glycine max Nutrition 0.000 description 2
• 102000009465 Growth Factor Receptors Human genes 0.000 description 2
• 108010009202 Growth Factor Receptors Proteins 0.000 description 2
• 239000007995 HEPES buffer Substances 0.000 description 2
• 101000622137 Homo sapiens P-selectin Proteins 0.000 description 2
• 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 2
• 241000343235 Maso Species 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 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
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
• 206010029113 Neovascularisation Diseases 0.000 description 2
• 239000000020 Nitrocellulose Substances 0.000 description 2
• 102100023472 P-selectin Human genes 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• 235000008331 Pinus X rigitaeda Nutrition 0.000 description 2
• 235000011613 Pinus brutia Nutrition 0.000 description 2
• 241000018646 Pinus brutia Species 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• 239000004793 Polystyrene Substances 0.000 description 2
• 102000013009 Pyruvate Kinase Human genes 0.000 description 2
• 108020005115 Pyruvate Kinase Proteins 0.000 description 2
• 208000017442 Retinal disease Diseases 0.000 description 2
• 206010038923 Retinopathy Diseases 0.000 description 2
• 101150060303 SOK2 gene Proteins 0.000 description 2
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
• 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 2
• 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 2
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
• 230000004913 activation Effects 0.000 description 2
• 230000001154 acute effect Effects 0.000 description 2
• 239000000654 additive Substances 0.000 description 2
• 239000000443 aerosol Substances 0.000 description 2
• 239000008272 agar Substances 0.000 description 2
• 235000010419 agar Nutrition 0.000 description 2
• 125000000539 amino acid group Chemical group 0.000 description 2
• 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 description 2
• 238000003782 apoptosis assay Methods 0.000 description 2
• 230000006907 apoptotic process Effects 0.000 description 2
• 239000000010 aprotic solvent Substances 0.000 description 2
• 210000001742 aqueous humor Anatomy 0.000 description 2
• 239000012298 atmosphere Substances 0.000 description 2
• 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• 210000000988 bone and bone Anatomy 0.000 description 2
• 229940098773 bovine serum albumin Drugs 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 2
• 239000001768 carboxy methyl cellulose Substances 0.000 description 2
• 230000010261 cell growth Effects 0.000 description 2
• MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
• 239000012230 colorless oil Substances 0.000 description 2
• 230000000052 comparative effect Effects 0.000 description 2
• 229910052802 copper Inorganic materials 0.000 description 2
• 239000010949 copper Substances 0.000 description 2
• 210000004087 cornea Anatomy 0.000 description 2
• 239000006184 cosolvent Substances 0.000 description 2
• 239000012043 crude product Substances 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• 239000008121 dextrose Substances 0.000 description 2
• 230000008034 disappearance Effects 0.000 description 2
• 238000009826 distribution Methods 0.000 description 2
• 125000004494 ethyl ester group Chemical group 0.000 description 2
• 238000000605 extraction Methods 0.000 description 2
• 239000010685 fatty oil Substances 0.000 description 2
• 239000012091 fetal bovine serum Substances 0.000 description 2
• 239000012467 final product Substances 0.000 description 2
• 125000001153 fluoro group Chemical group F* 0.000 description 2
• 235000019253 formic acid Nutrition 0.000 description 2
• 239000012634 fragment Substances 0.000 description 2
• 239000012458 free base Substances 0.000 description 2
• 229930195712 glutamate Natural products 0.000 description 2
• 125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 2
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
• 230000002779 inactivation Effects 0.000 description 2
• 208000015181 infectious disease Diseases 0.000 description 2
• 230000000977 initiatory effect Effects 0.000 description 2
• 238000003780 insertion Methods 0.000 description 2
• 230000037431 insertion Effects 0.000 description 2
• 102000006495 integrins Human genes 0.000 description 2
• 108010044426 integrins Proteins 0.000 description 2
• 230000003993 interaction Effects 0.000 description 2
• 239000011630 iodine Substances 0.000 description 2
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
• 238000002955 isolation Methods 0.000 description 2
• 239000002502 liposome Substances 0.000 description 2
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
• 235000019341 magnesium sulphate Nutrition 0.000 description 2
• 238000004519 manufacturing process Methods 0.000 description 2
• 230000007246 mechanism Effects 0.000 description 2
• 230000004060 metabolic process Effects 0.000 description 2
• 238000002156 mixing Methods 0.000 description 2
• 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
• UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
• 229920001220 nitrocellulos Polymers 0.000 description 2
• 210000000056 organ Anatomy 0.000 description 2
• 150000007530 organic bases Chemical class 0.000 description 2
• 239000003960 organic solvent Substances 0.000 description 2
• ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 2
• 239000005022 packaging material Substances 0.000 description 2
• 238000007911 parenteral administration Methods 0.000 description 2
• 230000000149 penetrating effect Effects 0.000 description 2
• WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 2
• 235000021317 phosphate Nutrition 0.000 description 2
• LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 2
• 229940068886 polyethylene glycol 300 Drugs 0.000 description 2
• 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
• 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
• 229940068968 polysorbate 80 Drugs 0.000 description 2
• 229920000053 polysorbate 80 Polymers 0.000 description 2
• 238000004262 preparative liquid chromatography Methods 0.000 description 2
• 230000005522 programmed cell death Effects 0.000 description 2
• 230000002062 proliferating effect Effects 0.000 description 2
• 230000002035 prolonged effect Effects 0.000 description 2
• 125000004076 pyridyl group Chemical group 0.000 description 2
• 238000010992 reflux Methods 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
• PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 2
• 229910052938 sodium sulfate Inorganic materials 0.000 description 2
• 235000011152 sodium sulphate Nutrition 0.000 description 2
• 239000007901 soft capsule Substances 0.000 description 2
• 239000012453 solvate Substances 0.000 description 2
• 238000001228 spectrum Methods 0.000 description 2
• SETMGIIITGNLAS-UHFFFAOYSA-N spizofurone Chemical compound O=C1C2=CC(C(=O)C)=CC=C2OC21CC2 SETMGIIITGNLAS-UHFFFAOYSA-N 0.000 description 2
• 229950001870 spizofurone Drugs 0.000 description 2
• 238000010186 staining Methods 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 239000004094 surface-active agent Substances 0.000 description 2
• 230000009747 swallowing Effects 0.000 description 2
• 239000000454 talc Substances 0.000 description 2
• 229910052623 talc Inorganic materials 0.000 description 2
• 235000012222 talc Nutrition 0.000 description 2
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 2
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
• 229940124597 therapeutic agent Drugs 0.000 description 2
• 230000007704 transition Effects 0.000 description 2
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
• JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 2
• 230000006459 vascular development Effects 0.000 description 2
• 239000013598 vector Substances 0.000 description 2
• 238000005406 washing Methods 0.000 description 2
• 230000003313 weakening effect Effects 0.000 description 2
• 238000010626 work up procedure Methods 0.000 description 2
• 239000008096 xylene Substances 0.000 description 2
• 150000003738 xylenes Chemical class 0.000 description 2
• HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 description 1
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
• KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
• LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
• PGOOBECODWQEAB-UHFFFAOYSA-N (E)-clothianidin Chemical compound [O-][N+](=O)\N=C(/NC)NCC1=CN=C(Cl)S1 PGOOBECODWQEAB-UHFFFAOYSA-N 0.000 description 1
• WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
• 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 1
• DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
• 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 1
• LQQKDSXCDXHLLF-UHFFFAOYSA-N 1,3-dibromopropan-2-one Chemical compound BrCC(=O)CBr LQQKDSXCDXHLLF-UHFFFAOYSA-N 0.000 description 1
• QHHHLHCCVDMOJI-UHFFFAOYSA-N 1,3-thiazol-4-amine Chemical class NC1=CSC=N1 QHHHLHCCVDMOJI-UHFFFAOYSA-N 0.000 description 1
• GCXPRJDKXBACNF-UHFFFAOYSA-N 1-(3-aminophenyl)-2-bromoethanone Chemical compound NC1=CC=CC(C(=O)CBr)=C1 GCXPRJDKXBACNF-UHFFFAOYSA-N 0.000 description 1
• CGXJUBDTCAAXAY-UHFFFAOYSA-N 1-(3-aminophenyl)propan-1-one Chemical compound CCC(=O)C1=CC=CC(N)=C1 CGXJUBDTCAAXAY-UHFFFAOYSA-N 0.000 description 1
• VWVZFHRDLPHBEG-UHFFFAOYSA-N 1-(chloromethyl)-4-methylsulfanylbenzene Chemical group CSC1=CC=C(CCl)C=C1 VWVZFHRDLPHBEG-UHFFFAOYSA-N 0.000 description 1
• VCGFSKNCUIRVDA-UHFFFAOYSA-N 1-[methyl(nitroso)amino]butyl acetate Chemical compound CCCC(OC(C)=O)N(C)N=O VCGFSKNCUIRVDA-UHFFFAOYSA-N 0.000 description 1
• HNEGJTWNOOWEMH-UHFFFAOYSA-N 1-fluoropropane Chemical group [CH2]CCF HNEGJTWNOOWEMH-UHFFFAOYSA-N 0.000 description 1
• IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
• 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
• SPMLMLQATWNZEE-UHFFFAOYSA-N 2-(chloromethyl)-1h-benzimidazole Chemical compound C1=CC=C2NC(CCl)=NC2=C1 SPMLMLQATWNZEE-UHFFFAOYSA-N 0.000 description 1
• BWCCPOQIMGGGQX-UHFFFAOYSA-N 2-(chloromethyl)-4,6-dimethoxypyrimidine Chemical compound COC1=CC(OC)=NC(CCl)=N1 BWCCPOQIMGGGQX-UHFFFAOYSA-N 0.000 description 1
• AJKIAERFLWQLAM-UHFFFAOYSA-N 2-(chloromethyl)-5-(4-chlorophenyl)-1,3,4-oxadiazole Chemical compound O1C(CCl)=NN=C1C1=CC=C(Cl)C=C1 AJKIAERFLWQLAM-UHFFFAOYSA-N 0.000 description 1
• WZEWEZMUYDNMCZ-UHFFFAOYSA-N 2-(chloromethyl)-6-methoxy-1h-benzimidazole Chemical compound COC1=CC=C2N=C(CCl)NC2=C1 WZEWEZMUYDNMCZ-UHFFFAOYSA-N 0.000 description 1
• NJWIMFZLESWFIM-UHFFFAOYSA-N 2-(chloromethyl)pyridine Chemical compound ClCC1=CC=CC=N1 NJWIMFZLESWFIM-UHFFFAOYSA-N 0.000 description 1
• JPMRGPPMXHGKRO-UHFFFAOYSA-N 2-(chloromethyl)pyridine hydrochloride Chemical compound Cl.ClCC1=CC=CC=N1 JPMRGPPMXHGKRO-UHFFFAOYSA-N 0.000 description 1
• DDEAEWMDOSXKBX-UHFFFAOYSA-N 2-(chloromethyl)quinoline Chemical compound C1=CC=CC2=NC(CCl)=CC=C21 DDEAEWMDOSXKBX-UHFFFAOYSA-N 0.000 description 1
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
• GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
• 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
• VFMGOJUUTAPPDA-UHFFFAOYSA-N 2-ethyl-5-methylpyrazole-3-carboxylic acid Chemical compound CCN1N=C(C)C=C1C(O)=O VFMGOJUUTAPPDA-UHFFFAOYSA-N 0.000 description 1
• HBAHZZVIEFRTEY-UHFFFAOYSA-N 2-heptylcyclohex-2-en-1-one Chemical compound CCCCCCCC1=CCCCC1=O HBAHZZVIEFRTEY-UHFFFAOYSA-N 0.000 description 1
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
• HZLCGUXUOFWCCN-UHFFFAOYSA-N 2-hydroxynonadecane-1,2,3-tricarboxylic acid Chemical compound CCCCCCCCCCCCCCCCC(C(O)=O)C(O)(C(O)=O)CC(O)=O HZLCGUXUOFWCCN-UHFFFAOYSA-N 0.000 description 1
• QCXCIYPOMMIBHO-UHFFFAOYSA-N 2-methyl-1,3-thiazole-5-carboxylic acid Chemical compound CC1=NC=C(C(O)=O)S1 QCXCIYPOMMIBHO-UHFFFAOYSA-N 0.000 description 1
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• GRNHLFULJDXJKR-UHFFFAOYSA-N 3-(2-sulfanylethyl)-1h-quinazoline-2,4-dione Chemical compound C1=CC=C2C(=O)N(CCS)C(=O)NC2=C1 GRNHLFULJDXJKR-UHFFFAOYSA-N 0.000 description 1
• YSNKGJCEHOJIDK-UHFFFAOYSA-N 3-(chloromethyl)-1,2,4-oxadiazole Chemical compound ClCC=1N=CON=1 YSNKGJCEHOJIDK-UHFFFAOYSA-N 0.000 description 1
• UBNGKQCKUVRCGR-UHFFFAOYSA-N 3-(chloromethyl)-5-(3,5-dimethyl-1,2-oxazol-4-yl)-1,2,4-oxadiazole Chemical compound CC1=NOC(C)=C1C1=NC(CCl)=NO1 UBNGKQCKUVRCGR-UHFFFAOYSA-N 0.000 description 1
• FEXTXBAFBURKGS-UHFFFAOYSA-N 3-(chloromethyl)-5-methyl-1,2-oxazole Chemical compound CC1=CC(CCl)=NO1 FEXTXBAFBURKGS-UHFFFAOYSA-N 0.000 description 1
• KHJYOJVUQYWASE-UHFFFAOYSA-N 3-(chloromethyl)-5-thiophen-3-yl-1,2,4-oxadiazole Chemical compound ClCC1=NOC(C2=CSC=C2)=N1 KHJYOJVUQYWASE-UHFFFAOYSA-N 0.000 description 1
• NJXPYZHXZZCTNI-UHFFFAOYSA-N 3-aminobenzonitrile Chemical compound NC1=CC=CC(C#N)=C1 NJXPYZHXZZCTNI-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• PRRZDZJYSJLDBS-UHFFFAOYSA-N 3-bromo-2-oxopropanoic acid Chemical compound OC(=O)C(=O)CBr PRRZDZJYSJLDBS-UHFFFAOYSA-N 0.000 description 1
• 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
• NUSXEDNPFNWFDQ-UHFFFAOYSA-N 3-chloro-2-(chloromethyl)-5-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CN=C(CCl)C(Cl)=C1 NUSXEDNPFNWFDQ-UHFFFAOYSA-N 0.000 description 1
• KKFQIFLHVDGQIW-UHFFFAOYSA-N 3-cyano-n-[(2-methylpropan-2-yl)oxy]benzamide Chemical compound CC(C)(C)ONC(=O)C1=CC=CC(C#N)=C1 KKFQIFLHVDGQIW-UHFFFAOYSA-N 0.000 description 1
• QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
• HKJUOMPYMPXLFS-UHFFFAOYSA-N 4-(4-hydroxy-3,5-diiodophenoxy)-3,5-diiodobenzoic acid Chemical compound IC1=CC(C(=O)O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 HKJUOMPYMPXLFS-UHFFFAOYSA-N 0.000 description 1
• VCTKYTBWZTZPHF-UHFFFAOYSA-N 4-(chloromethyl)-5-methyl-2-phenyl-1,3-oxazole Chemical compound ClCC1=C(C)OC(C=2C=CC=CC=2)=N1 VCTKYTBWZTZPHF-UHFFFAOYSA-N 0.000 description 1
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
• WSVCIWJKLYVDLA-UHFFFAOYSA-N 4-amino-2-(4-propan-2-ylanilino)-1,3-thiazole-5-carbothioamide Chemical compound C1=CC(C(C)C)=CC=C1NC1=NC(N)=C(C(N)=S)S1 WSVCIWJKLYVDLA-UHFFFAOYSA-N 0.000 description 1
• ZFOXYMYPSAEQEA-UHFFFAOYSA-N 4-amino-2-(4-sulfamoylanilino)-1,3-thiazole-5-carbothioamide Chemical compound NC1=C(C(=S)N)SC(NC=2C=CC(=CC=2)S(N)(=O)=O)=N1 ZFOXYMYPSAEQEA-UHFFFAOYSA-N 0.000 description 1
• KTBFNXHKAAHOFF-UHFFFAOYSA-N 4-amino-2-(tritylamino)-1,3-thiazole-5-carbothioamide Chemical compound NC1=C(C(=S)N)SC(NC(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 KTBFNXHKAAHOFF-UHFFFAOYSA-N 0.000 description 1
• YGKYNQLJZYSYEK-UHFFFAOYSA-N 4-carbamoyloxybenzoic acid Chemical compound NC(=O)OC1=CC=C(C(O)=O)C=C1 YGKYNQLJZYSYEK-UHFFFAOYSA-N 0.000 description 1
• NNMYRMGMVLMQAY-UHFFFAOYSA-N 4-chloropyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC(Cl)=CC=N1 NNMYRMGMVLMQAY-UHFFFAOYSA-N 0.000 description 1
• IMDUFDNFSJWYQT-UHFFFAOYSA-N 4-isothiocyanatobenzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=C(N=C=S)C=C1 IMDUFDNFSJWYQT-UHFFFAOYSA-N 0.000 description 1
• BJVYSQGEJHKTBW-UHFFFAOYSA-N 5-(chloromethyl)-3-(4-chlorophenyl)-1,2,4-oxadiazole Chemical compound O1C(CCl)=NC(C=2C=CC(Cl)=CC=2)=N1 BJVYSQGEJHKTBW-UHFFFAOYSA-N 0.000 description 1
• RYZHGEZWUMHELK-UHFFFAOYSA-N 5-(chloromethyl)-3-(4-chlorophenyl)-1h-1,2,4-triazole Chemical compound N1C(CCl)=NN=C1C1=CC=C(Cl)C=C1 RYZHGEZWUMHELK-UHFFFAOYSA-N 0.000 description 1
• PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 1
• DADXWROZAWLOFB-UHFFFAOYSA-N 5-chloro-4-(chloromethyl)thiadiazole Chemical compound ClCC=1N=NSC=1Cl DADXWROZAWLOFB-UHFFFAOYSA-N 0.000 description 1
• AFWKAIYTSPWWCA-UHFFFAOYSA-N 5-isothiocyanato-1,2,3-trimethoxybenzene Chemical compound COC1=CC(N=C=S)=CC(OC)=C1OC AFWKAIYTSPWWCA-UHFFFAOYSA-N 0.000 description 1
• UYDGNRLMYZMDOG-UHFFFAOYSA-N 5-methyl-1,3-thiazole-2-carboxylic acid Chemical compound CC1=CN=C(C(O)=O)S1 UYDGNRLMYZMDOG-UHFFFAOYSA-N 0.000 description 1
• RUKDIKJSGDVSIF-UHFFFAOYSA-N 5-phenyl-1,3-oxazole-4-carboxylic acid Chemical compound N1=COC(C=2C=CC=CC=2)=C1C(=O)O RUKDIKJSGDVSIF-UHFFFAOYSA-N 0.000 description 1
• VVTSPTCBHTWXMD-UHFFFAOYSA-N 6-morpholin-4-ylpyridin-3-amine Chemical compound N1=CC(N)=CC=C1N1CCOCC1 VVTSPTCBHTWXMD-UHFFFAOYSA-N 0.000 description 1
• MYLBTCQBKAKUTJ-UHFFFAOYSA-N 7-methyl-6,8-bis(methylsulfanyl)pyrrolo[1,2-a]pyrazine Chemical compound C1=CN=CC2=C(SC)C(C)=C(SC)N21 MYLBTCQBKAKUTJ-UHFFFAOYSA-N 0.000 description 1
• 101150065898 AVT5 gene Proteins 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• OQLZINXFSUDMHM-UHFFFAOYSA-N Acetamidine Chemical compound CC(N)=N OQLZINXFSUDMHM-UHFFFAOYSA-N 0.000 description 1
• 102100034608 Angiopoietin-2 Human genes 0.000 description 1
• 108010048036 Angiopoietin-2 Proteins 0.000 description 1
• 240000007087 Apium graveolens Species 0.000 description 1
• 235000015849 Apium graveolens Dulce Group Nutrition 0.000 description 1
• 235000010591 Appio Nutrition 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 206010003210 Arteriosclerosis Diseases 0.000 description 1
• CKLJMWTZIZZHCS-UHFFFAOYSA-N Aspartic acid Chemical compound OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 1
• 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
• 208000023275 Autoimmune disease Diseases 0.000 description 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
• ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
• 241000566113 Branta sandvicensis Species 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
• 101150079162 CHDH gene Proteins 0.000 description 1
• 235000017399 Caesalpinia tinctoria Nutrition 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• 208000017897 Carcinoma of esophagus Diseases 0.000 description 1
• WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
• 101100338312 Clostridium botulinum C phage HA-17 gene Proteins 0.000 description 1
• 102000016726 Coat Protein Complex I Human genes 0.000 description 1
• 108010092897 Coat Protein Complex I Proteins 0.000 description 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
• 241001327708 Coriaria sarmentosa Species 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 206010010996 Corneal degeneration Diseases 0.000 description 1
• 102000003909 Cyclin E Human genes 0.000 description 1
• 108090000257 Cyclin E Proteins 0.000 description 1
• 102100021906 Cyclin-O Human genes 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• 239000012623 DNA damaging agent Substances 0.000 description 1
• 230000033616 DNA repair Effects 0.000 description 1
• 101100481408 Danio rerio tie2 gene Proteins 0.000 description 1
• 101710088194 Dehydrogenase Proteins 0.000 description 1
• 229920002307 Dextran Polymers 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
• 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
• 101100411591 Dictyostelium discoideum rab8B gene Proteins 0.000 description 1
• RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
• 101100081489 Drosophila melanogaster Obp83a gene Proteins 0.000 description 1
• 241000792859 Enema Species 0.000 description 1
• 239000001856 Ethyl cellulose Substances 0.000 description 1
• ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
• 108091008794 FGF receptors Proteins 0.000 description 1
• 102000044168 Fibroblast Growth Factor Receptor Human genes 0.000 description 1
• 108010067715 Focal Adhesion Protein-Tyrosine Kinases Proteins 0.000 description 1
• 102000016621 Focal Adhesion Protein-Tyrosine Kinases Human genes 0.000 description 1
• 102100037813 Focal adhesion kinase 1 Human genes 0.000 description 1
• IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
• 208000031448 Genomic Instability Diseases 0.000 description 1
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• 244000068988 Glycine max Species 0.000 description 1
• 241001467044 Groundnut rosette assistor virus Species 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
• 229910052689 Holmium Inorganic materials 0.000 description 1
• 101000798320 Homo sapiens Bcl-2 homologous antagonist/killer Proteins 0.000 description 1
• 101000897441 Homo sapiens Cyclin-O Proteins 0.000 description 1
• 101000939500 Homo sapiens UBX domain-containing protein 11 Proteins 0.000 description 1
• 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 1
• 108091006905 Human Serum Albumin Proteins 0.000 description 1
• 102000008100 Human Serum Albumin Human genes 0.000 description 1
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
• 206010058490 Hyperoxia Diseases 0.000 description 1
• 206010021143 Hypoxia Diseases 0.000 description 1
• 208000007766 Kaposi sarcoma Diseases 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
• 102000003855 L-lactate dehydrogenase Human genes 0.000 description 1
• 108700023483 L-lactate dehydrogenases Proteins 0.000 description 1
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-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
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 241001446467 Mama Species 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 229920001367 Merrifield resin Polymers 0.000 description 1
• VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
• 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 description 1
• 108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 description 1
• 241001077660 Molo Species 0.000 description 1
• 101100481410 Mus musculus Tek gene Proteins 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 241000283965 Ochotona princeps Species 0.000 description 1
• 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
• 108010058846 Ovalbumin Proteins 0.000 description 1
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
• 241000282320 Panthera leo Species 0.000 description 1
• YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 1
• 108010020346 Polyglutamic Acid Proteins 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
• 102000003923 Protein Kinase C Human genes 0.000 description 1
• 108090000315 Protein Kinase C Proteins 0.000 description 1
• 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
• 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
• 101100065491 Rattus norvegicus Epha5 gene Proteins 0.000 description 1
• 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 description 1
• 108090000873 Receptor Protein-Tyrosine Kinases Proteins 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
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
• 229920002125 Sokalan® Polymers 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 108010090804 Streptavidin Proteins 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical class OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
• 210000001744 T-lymphocyte Anatomy 0.000 description 1
• 241000388430 Tara Species 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 244000162450 Taxus cuspidata Species 0.000 description 1
• 235000009065 Taxus cuspidata Nutrition 0.000 description 1
• 108010009978 Tec protein-tyrosine kinase Proteins 0.000 description 1
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-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
• 108010078814 Tumor Suppressor Protein p53 Proteins 0.000 description 1
• CCAZWUJBLXKBAY-ULZPOIKGSA-N Tutin Chemical compound C([C@]12[C@@H]3O[C@@H]3[C@@]3(O)[C@H]4C(=O)O[C@@H]([C@H]([C@]32C)O)[C@H]4C(=C)C)O1 CCAZWUJBLXKBAY-ULZPOIKGSA-N 0.000 description 1
• 102100029645 UBX domain-containing protein 11 Human genes 0.000 description 1
• 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 1
• 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 1
• 241000700605 Viruses Species 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
• ZPZHAUXTGFNYTN-UHFFFAOYSA-N [isothiocyanato(diphenyl)methyl]benzene Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(N=C=S)C1=CC=CC=C1 ZPZHAUXTGFNYTN-UHFFFAOYSA-N 0.000 description 1
• 230000002159 abnormal effect Effects 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• 150000001242 acetic acid derivatives Chemical class 0.000 description 1
• MANVMTSCCSAYSN-UHFFFAOYSA-N acetonitrile;2-methylpropan-2-ol Chemical compound CC#N.CC(C)(C)O MANVMTSCCSAYSN-UHFFFAOYSA-N 0.000 description 1
• 239000012445 acidic reagent Substances 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
• 239000012190 activator Substances 0.000 description 1
• 229940040563 agaric acid Drugs 0.000 description 1
• IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
• 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
• 230000004075 alteration Effects 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
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 239000004037 angiogenesis inhibitor Substances 0.000 description 1
• 210000002159 anterior chamber Anatomy 0.000 description 1
• 230000001028 anti-proliverative effect Effects 0.000 description 1
• 239000002246 antineoplastic agent Substances 0.000 description 1
• 239000011260 aqueous acid Substances 0.000 description 1
• 239000008365 aqueous carrier Substances 0.000 description 1
• 239000008346 aqueous phase Substances 0.000 description 1
• 239000008135 aqueous vehicle Substances 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 235000003704 aspartic acid Nutrition 0.000 description 1
• 239000005667 attractant Substances 0.000 description 1
• 230000004888 barrier function Effects 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• WXBLLCUINBKULX-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1 WXBLLCUINBKULX-UHFFFAOYSA-N 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
• OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
• 125000002619 bicyclic group Chemical group 0.000 description 1
• 229920000249 biocompatible polymer Polymers 0.000 description 1
• 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 1
• QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• 210000004204 blood vessel Anatomy 0.000 description 1
• 238000007664 blowing Methods 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 150000001649 bromium compounds Chemical class 0.000 description 1
• 230000005587 bubbling Effects 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 235000014121 butter Nutrition 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
• 229910052791 calcium Inorganic materials 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910000019 calcium carbonate Inorganic materials 0.000 description 1
• 235000010216 calcium carbonate Nutrition 0.000 description 1
• 239000001506 calcium phosphate Chemical class 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 235000011010 calcium phosphates Nutrition 0.000 description 1
• 230000009702 cancer cell proliferation Effects 0.000 description 1
• 239000001569 carbon dioxide Substances 0.000 description 1
• 229910002092 carbon dioxide Inorganic materials 0.000 description 1
• 229960004424 carbon dioxide Drugs 0.000 description 1
• 229910002091 carbon monoxide Inorganic materials 0.000 description 1
• 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 230000006369 cell cycle progression Effects 0.000 description 1
• 230000024245 cell differentiation Effects 0.000 description 1
• 230000003915 cell function Effects 0.000 description 1
• 230000009087 cell motility Effects 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 230000033077 cellular process Effects 0.000 description 1
• 229920002678 cellulose Chemical class 0.000 description 1
• 239000001913 cellulose Chemical class 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 238000002512 chemotherapy Methods 0.000 description 1
• 150000001805 chlorine compounds Chemical class 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• WBLIXGSTEMXDSM-UHFFFAOYSA-N chloromethane Chemical compound Cl[CH2] WBLIXGSTEMXDSM-UHFFFAOYSA-N 0.000 description 1
• 210000003161 choroid Anatomy 0.000 description 1
• 150000004777 chromones Chemical class 0.000 description 1
• 230000001684 chronic effect Effects 0.000 description 1
• 235000013985 cinnamic acid Nutrition 0.000 description 1
• 229930016911 cinnamic acid Natural products 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
• 229940125890 compound Ia Drugs 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 229940099112 cornstarch Drugs 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 230000001086 cytosolic effect Effects 0.000 description 1
• 125000005534 decanoate group Chemical class 0.000 description 1
• 239000008367 deionised water Substances 0.000 description 1
• 229910021641 deionized water Inorganic materials 0.000 description 1
• 238000012217 deletion Methods 0.000 description 1
• 230000037430 deletion Effects 0.000 description 1
• 230000003831 deregulation Effects 0.000 description 1
• 238000009795 derivation Methods 0.000 description 1
• 239000002274 desiccant Substances 0.000 description 1
• XAEWZDYWZHIUCT-UHFFFAOYSA-N desipramine hydrochloride Chemical compound [H+].[Cl-].C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 XAEWZDYWZHIUCT-UHFFFAOYSA-N 0.000 description 1
• 230000001066 destructive effect Effects 0.000 description 1
• 206010012601 diabetes mellitus Diseases 0.000 description 1
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
• 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
• 229940042935 dichlorodifluoromethane Drugs 0.000 description 1
• 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
• 235000014113 dietary fatty acids Nutrition 0.000 description 1
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
• 235000011180 diphosphates Nutrition 0.000 description 1
• 208000035475 disorder Diseases 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 238000006073 displacement reaction Methods 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 230000035622 drinking Effects 0.000 description 1
• 230000009977 dual effect Effects 0.000 description 1
• 229920001971 elastomer Polymers 0.000 description 1
• 238000007787 electrohydrodynamic spraying Methods 0.000 description 1
• 238000013504 emergency use authorization Methods 0.000 description 1
• 125000005610 enamide group Chemical group 0.000 description 1
• 210000004696 endometrium Anatomy 0.000 description 1
• 230000003511 endothelial effect Effects 0.000 description 1
• 239000007920 enema Substances 0.000 description 1
• 229940079360 enema for constipation Drugs 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 238000009585 enzyme analysis Methods 0.000 description 1
• 201000005619 esophageal carcinoma Diseases 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 1
• 235000019325 ethyl cellulose Nutrition 0.000 description 1
• 229920001249 ethyl cellulose Polymers 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 239000013604 expression vector Substances 0.000 description 1
• 208000030533 eye disease Diseases 0.000 description 1
• 210000000720 eyelash Anatomy 0.000 description 1
• 229930195729 fatty acid Natural products 0.000 description 1
• 239000000194 fatty acid Substances 0.000 description 1
• 238000002875 fluorescence polarization 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
• 150000004675 formic acid derivatives Chemical class 0.000 description 1
• 238000004108 freeze drying Methods 0.000 description 1
• 238000007710 freezing Methods 0.000 description 1
• 230000008014 freezing Effects 0.000 description 1
• 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
• 230000005714 functional activity Effects 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 108020001507 fusion proteins Proteins 0.000 description 1
• 102000037865 fusion proteins Human genes 0.000 description 1
• 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
• 229940014259 gelatin Drugs 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• 239000004220 glutamic acid Substances 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• 125000005456 glyceride group Chemical group 0.000 description 1
• 229940074045 glyceryl distearate Drugs 0.000 description 1
• 229940075507 glyceryl monostearate Drugs 0.000 description 1
• 239000008202 granule composition Substances 0.000 description 1
• 238000000227 grinding Methods 0.000 description 1
• 229960001867 guaiacol Drugs 0.000 description 1
• 125000001188 haloalkyl group Chemical group 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 201000011066 hemangioma Diseases 0.000 description 1
• 229920000669 heparin Polymers 0.000 description 1
• 229960002897 heparin Drugs 0.000 description 1
• MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical class CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
• 125000004404 heteroalkyl group Chemical group 0.000 description 1
• 125000005842 heteroatom Chemical group 0.000 description 1
• 125000000623 heterocyclic group Chemical group 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 231100000171 higher toxicity Toxicity 0.000 description 1
• 230000001744 histochemical effect Effects 0.000 description 1
• 235000012907 honey Nutrition 0.000 description 1
• 102000056701 human BAK1 Human genes 0.000 description 1
• 102000055590 human KDR Human genes 0.000 description 1
• 229920002674 hyaluronan Polymers 0.000 description 1
• 229960003160 hyaluronic acid Drugs 0.000 description 1
• 229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
• 238000007327 hydrogenolysis reaction Methods 0.000 description 1
• 229920001600 hydrophobic polymer Polymers 0.000 description 1
• 229960004337 hydroquinone Drugs 0.000 description 1
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
• 230000000222 hyperoxic effect Effects 0.000 description 1
• 230000007954 hypoxia Effects 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 238000002513 implantation Methods 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 229910052738 indium Inorganic materials 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 208000027866 inflammatory disease Diseases 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 230000031146 intracellular signal transduction Effects 0.000 description 1
• 238000010255 intramuscular injection Methods 0.000 description 1
• 239000007927 intramuscular injection Substances 0.000 description 1
• 150000004694 iodide salts Chemical class 0.000 description 1
• 229920003303 ion-exchange polymer Polymers 0.000 description 1
• 229910052742 iron Inorganic materials 0.000 description 1
• 229940047889 isobutyramide Drugs 0.000 description 1
• KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical class 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
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 150000002540 isothiocyanates Chemical class 0.000 description 1
• 125000001810 isothiocyanato group Chemical group *N=C=S 0.000 description 1
• 239000000644 isotonic solution Substances 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 208000017169 kidney disease Diseases 0.000 description 1
• 150000002596 lactones Chemical class 0.000 description 1
• GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
• 108010052968 leupeptin Proteins 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 239000006194 liquid suspension Substances 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
• 230000033001 locomotion Effects 0.000 description 1
• 230000005923 long-lasting effect Effects 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 150000002688 maleic acid derivatives Chemical class 0.000 description 1
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
• 150000002690 malonic acid derivatives Chemical class 0.000 description 1
• WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 125000005905 mesyloxy group Chemical group 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 125000005341 metaphosphate group Chemical group 0.000 description 1
• 229930182817 methionine Natural products 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 1
• WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 230000000394 mitotic effect Effects 0.000 description 1
• 229910052750 molybdenum Inorganic materials 0.000 description 1
• 125000002950 monocyclic group Chemical group 0.000 description 1
• 230000035772 mutation Effects 0.000 description 1
• JMJUHQGPXJPKRH-UHFFFAOYSA-N n-[3-(2-bromoacetyl)phenyl]-5-chlorothiophene-2-carboxamide Chemical compound S1C(Cl)=CC=C1C(=O)NC1=CC=CC(C(=O)CBr)=C1 JMJUHQGPXJPKRH-UHFFFAOYSA-N 0.000 description 1
• NBUKMHXINQOFDI-UHFFFAOYSA-N n-[4-(chloromethyl)-1,3-thiazol-2-yl]acetamide Chemical compound CC(=O)NC1=NC(CCl)=CS1 NBUKMHXINQOFDI-UHFFFAOYSA-N 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• 102000037979 non-receptor tyrosine kinases Human genes 0.000 description 1
• 108091008046 non-receptor tyrosine kinases Proteins 0.000 description 1
• 231100000956 nontoxicity Toxicity 0.000 description 1
• 210000001331 nose Anatomy 0.000 description 1
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
• 150000007523 nucleic acids Chemical class 0.000 description 1
• 102000039446 nucleic acids Human genes 0.000 description 1
• 108020004707 nucleic acids Proteins 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical class CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 239000004006 olive oil Substances 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 239000006186 oral dosage form Substances 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 229920000620 organic polymer Polymers 0.000 description 1
• 229940092253 ovalbumin Drugs 0.000 description 1
• 230000002018 overexpression Effects 0.000 description 1
• 230000027758 ovulation cycle Effects 0.000 description 1
• WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
• 150000003891 oxalate salts Chemical class 0.000 description 1
• GNWXVOQHLPBSSR-UHFFFAOYSA-N oxolane;toluene Chemical compound C1CCOC1.CC1=CC=CC=C1 GNWXVOQHLPBSSR-UHFFFAOYSA-N 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
• 201000002528 pancreatic cancer Diseases 0.000 description 1
• 208000008443 pancreatic carcinoma Diseases 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 230000007170 pathology Effects 0.000 description 1
• 235000010987 pectin Nutrition 0.000 description 1
• 239000001814 pectin Substances 0.000 description 1
• 229920001277 pectin Polymers 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 239000000816 peptidomimetic Substances 0.000 description 1
• 239000008024 pharmaceutical diluent Substances 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 239000008363 phosphate buffer Substances 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• DHRLEVQXOMLTIM-UHFFFAOYSA-N phosphoric acid;trioxomolybdenum Chemical compound O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.OP(O)(O)=O DHRLEVQXOMLTIM-UHFFFAOYSA-N 0.000 description 1
• 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
• 230000035790 physiological processes and functions Effects 0.000 description 1
• 239000002504 physiological saline solution Substances 0.000 description 1
• 239000000049 pigment Substances 0.000 description 1
• 239000004014 plasticizer Substances 0.000 description 1
• 229920000767 polyaniline Polymers 0.000 description 1
• 125000003367 polycyclic group Chemical group 0.000 description 1
• 229920002643 polyglutamic acid Polymers 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 229920001282 polysaccharide Polymers 0.000 description 1
• 239000005017 polysaccharide Substances 0.000 description 1
• 150000004804 polysaccharides Chemical class 0.000 description 1
• 229920002223 polystyrene Polymers 0.000 description 1
• 230000035409 positive regulation of cell proliferation Effects 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
• 229920001592 potato starch Polymers 0.000 description 1
• 229940116317 potato starch Drugs 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• 229940080818 propionamide Drugs 0.000 description 1
• UORVCLMRJXCDCP-UHFFFAOYSA-N propynoic acid Chemical class OC(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-N 0.000 description 1
• 230000017854 proteolysis Effects 0.000 description 1
• LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• 150000003222 pyridines Chemical class 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 238000010791 quenching Methods 0.000 description 1
• QZZYYBQGTSGDPP-UHFFFAOYSA-N quinoline-3-carbonitrile Chemical class C1=CC=CC2=CC(C#N)=CN=C21 QZZYYBQGTSGDPP-UHFFFAOYSA-N 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 150000003254 radicals Chemical class 0.000 description 1
• 230000002285 radioactive effect Effects 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• 239000002994 raw material Substances 0.000 description 1
• 239000000376 reactant Substances 0.000 description 1
• 230000022983 regulation of cell cycle Effects 0.000 description 1
• 230000026267 regulation of growth Effects 0.000 description 1
• 230000010076 replication Effects 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 229960001755 resorcinol Drugs 0.000 description 1
• 229940100486 rice starch Drugs 0.000 description 1
• 238000007363 ring formation reaction Methods 0.000 description 1
• 238000002390 rotary evaporation Methods 0.000 description 1
• 239000012266 salt solution Substances 0.000 description 1
• CXMXRPHRNRROMY-UHFFFAOYSA-N sebacic acid Chemical class OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 230000028327 secretion Effects 0.000 description 1
• 230000001953 sensory effect Effects 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 230000035939 shock Effects 0.000 description 1
• 230000011664 signaling Effects 0.000 description 1
• 239000000779 smoke Substances 0.000 description 1
• 235000010413 sodium alginate Nutrition 0.000 description 1
• 239000000661 sodium alginate Substances 0.000 description 1
• 229940005550 sodium alginate Drugs 0.000 description 1
• ZMRHBJQLCDZMAH-UHFFFAOYSA-M sodium chloride hydrate hydrochloride Chemical compound [OH-].[Na+].Cl.Cl ZMRHBJQLCDZMAH-UHFFFAOYSA-M 0.000 description 1
• 239000011775 sodium fluoride Substances 0.000 description 1
• 235000013024 sodium fluoride Nutrition 0.000 description 1
• CMZUMMUJMWNLFH-UHFFFAOYSA-N sodium metavanadate Chemical compound [Na+].[O-][V](=O)=O CMZUMMUJMWNLFH-UHFFFAOYSA-N 0.000 description 1
• 239000012439 solid excipient Substances 0.000 description 1
• 238000003797 solvolysis reaction Methods 0.000 description 1
• 238000002798 spectrophotometry method Methods 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 230000000087 stabilizing effect Effects 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 125000005504 styryl group Chemical group 0.000 description 1
• TYFQFVWCELRYAO-UHFFFAOYSA-N suberic acid Chemical class OC(=O)CCCCCCC(O)=O TYFQFVWCELRYAO-UHFFFAOYSA-N 0.000 description 1
• 125000000547 substituted alkyl group Chemical group 0.000 description 1
• 125000003107 substituted aryl group Chemical group 0.000 description 1
• 150000003890 succinate salts Chemical class 0.000 description 1
• 239000001384 succinic acid Substances 0.000 description 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
• 229910052717 sulfur Chemical group 0.000 description 1
• 239000011593 sulfur Chemical group 0.000 description 1
• 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
• 239000013589 supplement Substances 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 239000002511 suppository base Substances 0.000 description 1
• 230000001629 suppression Effects 0.000 description 1
• 238000013268 sustained release Methods 0.000 description 1
• 239000012730 sustained-release form Substances 0.000 description 1
• 238000007910 systemic administration Methods 0.000 description 1
• 239000003826 tablet Substances 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 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
• DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
• CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
• 125000005306 thianaphthenyl group Chemical group 0.000 description 1
• 150000007979 thiazole derivatives Chemical class 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 125000003396 thiol group Chemical group [H]S* 0.000 description 1
• 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
• 230000036962 time dependent Effects 0.000 description 1
• KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
• 239000004408 titanium dioxide Substances 0.000 description 1
• 238000004448 titration Methods 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
• 150000003626 triacylglycerols Chemical class 0.000 description 1
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical class [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
• 229940029284 trichlorofluoromethane Drugs 0.000 description 1
• 210000004881 tumor cell Anatomy 0.000 description 1
• 210000004291 uterus Anatomy 0.000 description 1
• 229910052720 vanadium Inorganic materials 0.000 description 1
• 230000006444 vascular growth Effects 0.000 description 1
• 230000008728 vascular permeability Effects 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 210000003462 vein Anatomy 0.000 description 1
• 238000012800 visualization Methods 0.000 description 1
• 229940100445 wheat starch Drugs 0.000 description 1
• 230000029663 wound healing Effects 0.000 description 1
• 210000005253 yeast cell Anatomy 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1
• 229910000166 zirconium phosphate Inorganic materials 0.000 description 1