CZ20021974A3 - Substituované ftalocyaniny, způsob jejich výroby a farmaceutický prostředek obsahující tyto sloučeniny - Google Patents

Info

Publication number

CZ20021974A3

CZ20021974A3 CZ20021974A CZ20021974A CZ20021974A3 CZ 20021974 A3 CZ20021974 A3 CZ 20021974A3 CZ 20021974 A CZ20021974 A CZ 20021974A CZ 20021974 A CZ20021974 A CZ 20021974A CZ 20021974 A3 CZ20021974 A3 CZ 20021974A3

Authority

CZ

Czechia

Prior art keywords

group

optionally substituted

formula

carbon atoms

substituted

Prior art date

1999-12-08

Links

• Espacenet
• Global Dossier
• Discuss

• 238000002360 preparation method Methods 0.000 title claims abstract description 119
• 238000000034 method Methods 0.000 title claims abstract description 108
• 230000008569 process Effects 0.000 title claims abstract description 39
• 150000001875 compounds Chemical class 0.000 title description 72
• 239000000825 pharmaceutical preparation Substances 0.000 title 1
• -1 phthalonitrile sulfonate esters Chemical class 0.000 claims abstract description 206
• 229920006391 phthalonitrile polymer Polymers 0.000 claims abstract description 162
• 125000004432 carbon atom Chemical group C* 0.000 claims description 195
• 125000001424 substituent group Chemical group 0.000 claims description 127
• IEQIEDJGQAUEQZ-UHFFFAOYSA-N phthalocyanine Chemical class N1C(N=C2C3=CC=CC=C3C(N=C3C4=CC=CC=C4C(=N4)N3)=N2)=C(C=CC=C2)C2=C1N=C1C2=CC=CC=C2C4=N1 IEQIEDJGQAUEQZ-UHFFFAOYSA-N 0.000 claims description 124
• 238000006243 chemical reaction Methods 0.000 claims description 103
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 101
• 125000000217 alkyl group Chemical group 0.000 claims description 100
• XQZYPMVTSDWCCE-UHFFFAOYSA-N phthalonitrile Chemical class N#CC1=CC=CC=C1C#N XQZYPMVTSDWCCE-UHFFFAOYSA-N 0.000 claims description 95
• 125000001153 fluoro group Chemical group F* 0.000 claims description 80
• 125000003342 alkenyl group Chemical group 0.000 claims description 77
• 239000011701 zinc Substances 0.000 claims description 76
• 229910052725 zinc Inorganic materials 0.000 claims description 73
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 64
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 60
• 229910052801 chlorine Inorganic materials 0.000 claims description 57
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 51
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 49
• 229910052731 fluorine Inorganic materials 0.000 claims description 48
• 125000003118 aryl group Chemical group 0.000 claims description 44
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 44
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 42
• 229910052794 bromium Inorganic materials 0.000 claims description 42
• 125000001072 heteroaryl group Chemical group 0.000 claims description 42
• 239000000460 chlorine Substances 0.000 claims description 41
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 40
• 229910052763 palladium Inorganic materials 0.000 claims description 40
• 229910052740 iodine Inorganic materials 0.000 claims description 36
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 35
• 239000003153 chemical reaction reagent Substances 0.000 claims description 32
• 230000005855 radiation Effects 0.000 claims description 31
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 30
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 28
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 27
• 239000011737 fluorine Substances 0.000 claims description 27
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 26
• 125000000304 alkynyl group Chemical group 0.000 claims description 25
• 125000001246 bromo group Chemical group Br* 0.000 claims description 24
• 229910052739 hydrogen Inorganic materials 0.000 claims description 23
• 125000003107 substituted aryl group Chemical group 0.000 claims description 23
• 239000001257 hydrogen Substances 0.000 claims description 22
• 229920000642 polymer Polymers 0.000 claims description 21
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
• 229920006395 saturated elastomer Polymers 0.000 claims description 19
• 125000005017 substituted alkenyl group Chemical group 0.000 claims description 19
• 125000004426 substituted alkynyl group Chemical group 0.000 claims description 19
• 206010028980 Neoplasm Diseases 0.000 claims description 18
• 229910052751 metal Inorganic materials 0.000 claims description 18
• 239000002184 metal Substances 0.000 claims description 18
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 18
• 229910052710 silicon Inorganic materials 0.000 claims description 18
• 239000010703 silicon Substances 0.000 claims description 18
• 150000002148 esters Chemical class 0.000 claims description 17
• 229910052759 nickel Inorganic materials 0.000 claims description 17
• 239000000126 substance Substances 0.000 claims description 16
• XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 15
• 238000002428 photodynamic therapy Methods 0.000 claims description 15
• 229910052799 carbon Inorganic materials 0.000 claims description 14
• 150000004820 halides Chemical class 0.000 claims description 14
• 239000011777 magnesium Substances 0.000 claims description 14
• 229910052749 magnesium Inorganic materials 0.000 claims description 13
• 229920001184 polypeptide Polymers 0.000 claims description 13
• 102000004196 processed proteins & peptides Human genes 0.000 claims description 13
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 13
• 102000004169 proteins and genes Human genes 0.000 claims description 13
• 108090000623 proteins and genes Proteins 0.000 claims description 13
• MPAIWVOBMLSHQA-UHFFFAOYSA-N 3,6-dihydroxybenzene-1,2-dicarbonitrile Chemical class OC1=CC=C(O)C(C#N)=C1C#N MPAIWVOBMLSHQA-UHFFFAOYSA-N 0.000 claims description 12
• 150000001413 amino acids Chemical class 0.000 claims description 12
• 150000001720 carbohydrates Chemical class 0.000 claims description 12
• 239000003795 chemical substances by application Substances 0.000 claims description 12
• 235000014113 dietary fatty acids Nutrition 0.000 claims description 12
• 239000000194 fatty acid Chemical group 0.000 claims description 12
• 229930195729 fatty acid Chemical group 0.000 claims description 12
• 150000004665 fatty acids Chemical group 0.000 claims description 12
• 150000004676 glycans Chemical class 0.000 claims description 12
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
• 150000007523 nucleic acids Chemical group 0.000 claims description 12
• 108020004707 nucleic acids Chemical group 0.000 claims description 12
• 102000039446 nucleic acids Human genes 0.000 claims description 12
• 239000008194 pharmaceutical composition Substances 0.000 claims description 12
• 229920001282 polysaccharide Polymers 0.000 claims description 12
• 239000005017 polysaccharide Substances 0.000 claims description 12
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 11
• 238000004519 manufacturing process Methods 0.000 claims description 11
• 229910052782 aluminium Inorganic materials 0.000 claims description 10
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 10
• 125000004429 atom Chemical group 0.000 claims description 10
• 125000002346 iodo group Chemical group I* 0.000 claims description 10
• 201000010099 disease Diseases 0.000 claims description 9
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
• 230000003647 oxidation Effects 0.000 claims description 9
• 238000007254 oxidation reaction Methods 0.000 claims description 9
• 229910052697 platinum Inorganic materials 0.000 claims description 9
• ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 8
• 238000006555 catalytic reaction Methods 0.000 claims description 8
• 206010020718 hyperplasia Diseases 0.000 claims description 8
• 208000031295 Animal disease Diseases 0.000 claims description 7
• 229910001509 metal bromide Inorganic materials 0.000 claims description 7
• 229910044991 metal oxide Inorganic materials 0.000 claims description 7
• 150000004706 metal oxides Chemical class 0.000 claims description 7
• 230000002792 vascular Effects 0.000 claims description 7
• 229910052796 boron Inorganic materials 0.000 claims description 6
• 230000004663 cell proliferation Effects 0.000 claims description 6
• 229910052802 copper Inorganic materials 0.000 claims description 6
• 239000010949 copper Substances 0.000 claims description 6
• 238000004132 cross linking Methods 0.000 claims description 6
• 229910001510 metal chloride Inorganic materials 0.000 claims description 6
• 201000004624 Dermatitis Diseases 0.000 claims description 5
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
• 201000004681 Psoriasis Diseases 0.000 claims description 5
• 238000005804 alkylation reaction Methods 0.000 claims description 5
• 208000010668 atopic eczema Diseases 0.000 claims description 5
• 238000006880 cross-coupling reaction Methods 0.000 claims description 5
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 5
• 239000012038 nucleophile Substances 0.000 claims description 5
• 150000003839 salts Chemical class 0.000 claims description 5
• 208000037260 Atherosclerotic Plaque Diseases 0.000 claims description 4
• 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 4
• 208000031220 Hemophilia Diseases 0.000 claims description 4
• 208000009292 Hemophilia A Diseases 0.000 claims description 4
• 206010020649 Hyperkeratosis Diseases 0.000 claims description 4
• 208000001126 Keratosis Diseases 0.000 claims description 4
• 208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 4
• 206010057469 Vascular stenosis Diseases 0.000 claims description 4
• 230000029936 alkylation Effects 0.000 claims description 4
• 206010003246 arthritis Diseases 0.000 claims description 4
• 239000003085 diluting agent Substances 0.000 claims description 4
• 239000003814 drug Substances 0.000 claims description 4
• 230000002538 fungal effect Effects 0.000 claims description 4
• 125000005843 halogen group Chemical group 0.000 claims description 4
• 230000002757 inflammatory effect Effects 0.000 claims description 4
• 239000011630 iodine Substances 0.000 claims description 4
• 230000003211 malignant effect Effects 0.000 claims description 4
• 201000008482 osteoarthritis Diseases 0.000 claims description 4
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
• 230000003612 virological effect Effects 0.000 claims description 4
• 108091000054 Prion Proteins 0.000 claims description 3
• 102000029797 Prion Human genes 0.000 claims description 3
• 230000002152 alkylating effect Effects 0.000 claims description 3
• 230000001580 bacterial effect Effects 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 2
• XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 claims description 2
• 201000005962 mycosis fungoides Diseases 0.000 claims description 2
• 125000003275 alpha amino acid group Chemical group 0.000 claims 1
• 125000004433 nitrogen atom Chemical group N* 0.000 claims 1
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 447
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 327
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 229
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 182
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 166
• 239000000203 mixture Substances 0.000 description 152
• 239000000243 solution Substances 0.000 description 148
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 111
• 238000005481 NMR spectroscopy Methods 0.000 description 101
• 239000011541 reaction mixture Substances 0.000 description 93
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 90
• 239000000047 product Substances 0.000 description 84
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 81
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 70
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 69
• 239000003208 petroleum Substances 0.000 description 64
• 239000002904 solvent Substances 0.000 description 62
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 61
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 60
• 239000007787 solid Substances 0.000 description 56
• GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 50
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
• 238000010992 reflux Methods 0.000 description 46
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 46
• 238000009835 boiling Methods 0.000 description 45
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 44
• 238000007792 addition Methods 0.000 description 43
• KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 40
• DSZGQEHPKNNPFU-UHFFFAOYSA-N 3,6-didecylbenzene-1,2-dicarbonitrile Chemical compound CCCCCCCCCCC1=CC=C(CCCCCCCCCC)C(C#N)=C1C#N DSZGQEHPKNNPFU-UHFFFAOYSA-N 0.000 description 37
• 238000010898 silica gel chromatography Methods 0.000 description 37
• 239000002585 base Substances 0.000 description 36
• 229910052757 nitrogen Inorganic materials 0.000 description 36
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
• 238000001816 cooling Methods 0.000 description 33
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 31
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
• 239000012267 brine Substances 0.000 description 30
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 30
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 25
• 230000015572 biosynthetic process Effects 0.000 description 25
• 239000003054 catalyst Substances 0.000 description 23
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 23
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 22
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 22
• 229910052786 argon Inorganic materials 0.000 description 22
• 230000000875 corresponding effect Effects 0.000 description 22
• 239000003480 eluent Substances 0.000 description 22
• 238000001704 evaporation Methods 0.000 description 22
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
• 210000004027 cell Anatomy 0.000 description 21
• 238000004440 column chromatography Methods 0.000 description 21
• 230000008020 evaporation Effects 0.000 description 21
• 230000002093 peripheral effect Effects 0.000 description 20
• AYGKNJJGSMKDPA-UHFFFAOYSA-N 4-bromo-3,6-dibutoxybenzene-1,2-dicarbonitrile Chemical compound CCCCOC1=CC(Br)=C(OCCCC)C(C#N)=C1C#N AYGKNJJGSMKDPA-UHFFFAOYSA-N 0.000 description 19
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 19
• 239000000741 silica gel Substances 0.000 description 19
• 229910002027 silica gel Inorganic materials 0.000 description 19
• ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 18
• 239000012043 crude product Substances 0.000 description 18
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 17
• YZYKBQUWMPUVEN-UHFFFAOYSA-N zafuleptine Chemical compound OC(=O)CCCCCC(C(C)C)NCC1=CC=C(F)C=C1 YZYKBQUWMPUVEN-UHFFFAOYSA-N 0.000 description 17
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 16
• 239000013078 crystal Substances 0.000 description 16
• 239000003921 oil Substances 0.000 description 16
• 238000003786 synthesis reaction Methods 0.000 description 16
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 15
• 238000006467 substitution reaction Methods 0.000 description 15
• 238000004809 thin layer chromatography Methods 0.000 description 15
• FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo(3.3.1)nonane Chemical compound C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 14
• FCAPKPPCJBYHEC-UHFFFAOYSA-N [2,3-dicyano-4-(trifluoromethylsulfonyloxy)phenyl] trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC1=CC=C(OS(=O)(=O)C(F)(F)F)C(C#N)=C1C#N FCAPKPPCJBYHEC-UHFFFAOYSA-N 0.000 description 14
• 238000001914 filtration Methods 0.000 description 14
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 13
• 238000001953 recrystallisation Methods 0.000 description 13
• 239000000725 suspension Substances 0.000 description 13
• JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 13
• AFFLGGQVNFXPEV-UHFFFAOYSA-N 1-decene Chemical compound CCCCCCCCC=C AFFLGGQVNFXPEV-UHFFFAOYSA-N 0.000 description 12
• OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 12
• AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 12
• 230000000155 isotopic effect Effects 0.000 description 12
• 229910052744 lithium Inorganic materials 0.000 description 12
• 238000001906 matrix-assisted laser desorption--ionisation mass spectrometry Methods 0.000 description 12
• 125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 12
• HAAHMAILBWIUSO-UHFFFAOYSA-N 4,5-dibromo-3,6-dibutoxybenzene-1,2-dicarbonitrile Chemical compound CCCCOC1=C(Br)C(Br)=C(OCCCC)C(C#N)=C1C#N HAAHMAILBWIUSO-UHFFFAOYSA-N 0.000 description 11
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 11
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 11
• 239000002274 desiccant Substances 0.000 description 11
• 239000000706 filtrate Substances 0.000 description 11
• 238000002844 melting Methods 0.000 description 11
• 230000008018 melting Effects 0.000 description 11
• 239000012044 organic layer Substances 0.000 description 11
• 238000003756 stirring Methods 0.000 description 11
• FDGUZCMQOHCDOY-UHFFFAOYSA-M [I-].CCCCCCCCCC[Zn+] Chemical compound [I-].CCCCCCCCCC[Zn+] FDGUZCMQOHCDOY-UHFFFAOYSA-M 0.000 description 10
• 229960000583 acetic acid Drugs 0.000 description 10
• 235000014633 carbohydrates Nutrition 0.000 description 10
• HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 10
• 239000000843 powder Substances 0.000 description 10
• 239000007858 starting material Substances 0.000 description 10
• WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 10
• 239000012300 argon atmosphere Substances 0.000 description 9
• 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 9
• 125000000524 functional group Chemical group 0.000 description 9
• 150000002431 hydrogen Chemical class 0.000 description 9
• 239000000463 material Substances 0.000 description 9
• 229910000029 sodium carbonate Inorganic materials 0.000 description 9
• 229910052720 vanadium Inorganic materials 0.000 description 9
• 229910021595 Copper(I) iodide Inorganic materials 0.000 description 8
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
• 239000007983 Tris buffer Substances 0.000 description 8
• 230000005670 electromagnetic radiation Effects 0.000 description 8
• 239000012362 glacial acetic acid Substances 0.000 description 8
• 238000010438 heat treatment Methods 0.000 description 8
• 239000002609 medium Substances 0.000 description 8
• 239000003504 photosensitizing agent Substances 0.000 description 8
• 238000007363 ring formation reaction Methods 0.000 description 8
• PUFIXALSROVACG-UHFFFAOYSA-N 4,5-dibromo-3,6-dihydroxybenzene-1,2-dicarbonitrile Chemical compound OC1=C(Br)C(Br)=C(O)C(C#N)=C1C#N PUFIXALSROVACG-UHFFFAOYSA-N 0.000 description 7
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 7
• LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 7
• 125000004093 cyano group Chemical group *C#N 0.000 description 7
• 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 7
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 7
• 239000002502 liposome Substances 0.000 description 7
• ZBRJXVVKPBZPAN-UHFFFAOYSA-L nickel(2+);triphenylphosphane;dichloride Chemical compound [Cl-].[Cl-].[Ni+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 ZBRJXVVKPBZPAN-UHFFFAOYSA-L 0.000 description 7
• 230000003287 optical effect Effects 0.000 description 7
• 229910000027 potassium carbonate Inorganic materials 0.000 description 7
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 7
• 239000011592 zinc chloride Substances 0.000 description 7
• 235000005074 zinc chloride Nutrition 0.000 description 7
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 6
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
• ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 description 6
• 239000002253 acid Substances 0.000 description 6
• 150000001335 aliphatic alkanes Chemical class 0.000 description 6
• 150000001336 alkenes Chemical class 0.000 description 6
• 201000011510 cancer Diseases 0.000 description 6
• 230000000694 effects Effects 0.000 description 6
• 239000010408 film Substances 0.000 description 6
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
• 239000012299 nitrogen atmosphere Substances 0.000 description 6
• 229910052760 oxygen Inorganic materials 0.000 description 6
• 239000002244 precipitate Substances 0.000 description 6
• 238000000746 purification Methods 0.000 description 6
• 150000003254 radicals Chemical class 0.000 description 6
• 239000000523 sample Substances 0.000 description 6
• 230000007704 transition Effects 0.000 description 6
• 239000004246 zinc acetate Substances 0.000 description 6
• KYPOHTVBFVELTG-OWOJBTEDSA-N (e)-but-2-enedinitrile Chemical compound N#C\C=C\C#N KYPOHTVBFVELTG-OWOJBTEDSA-N 0.000 description 5
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 5
• NTJBPRBBLQKOTL-UHFFFAOYSA-N 3,6-dibutoxy-4-[4-(hydroxymethyl)phenyl]benzene-1,2-dicarbonitrile Chemical compound N#CC1=C(C#N)C(OCCCC)=CC(C=2C=CC(CO)=CC=2)=C1OCCCC NTJBPRBBLQKOTL-UHFFFAOYSA-N 0.000 description 5
• SKTSZLTUDJZCEX-UHFFFAOYSA-N 3,6-diphenylbenzene-1,2-dicarbonitrile Chemical compound N#CC=1C(C#N)=C(C=2C=CC=CC=2)C=CC=1C1=CC=CC=C1 SKTSZLTUDJZCEX-UHFFFAOYSA-N 0.000 description 5
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 5
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 5
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 5
• 101150003085 Pdcl gene Proteins 0.000 description 5
• ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 5
• 229910021529 ammonia Inorganic materials 0.000 description 5
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 5
• 229910000024 caesium carbonate Inorganic materials 0.000 description 5
• 239000011575 calcium Substances 0.000 description 5
• 239000000969 carrier Substances 0.000 description 5
• 238000009396 hybridization Methods 0.000 description 5
• 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 5
• 239000001301 oxygen Chemical group 0.000 description 5
• 239000012071 phase Substances 0.000 description 5
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
• 239000002243 precursor Substances 0.000 description 5
• 238000001228 spectrum Methods 0.000 description 5
• 229910052718 tin Inorganic materials 0.000 description 5
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
• GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 description 4
• SKIDNYUZJPMKFC-UHFFFAOYSA-N 1-iododecane Chemical compound CCCCCCCCCCI SKIDNYUZJPMKFC-UHFFFAOYSA-N 0.000 description 4
• ZWDXFPRCFLWNBO-UHFFFAOYSA-N 3,6-bis(4-methoxyphenyl)benzene-1,2-dicarbonitrile Chemical compound C1=CC(OC)=CC=C1C(C(=C1C#N)C#N)=CC=C1C1=CC=C(OC)C=C1 ZWDXFPRCFLWNBO-UHFFFAOYSA-N 0.000 description 4
• PXLFZVNSJRPRPT-UHFFFAOYSA-N 3,6-bis(6-imidazol-1-ylhexyl)benzene-1,2-dicarbonitrile Chemical compound C1=CC(CCCCCCN2C=NC=C2)=C(C#N)C(C#N)=C1CCCCCCN1C=CN=C1 PXLFZVNSJRPRPT-UHFFFAOYSA-N 0.000 description 4
• PKUNOLIHEQYMCI-UHFFFAOYSA-N 3,6-bis(dodecylsulfanyl)benzene-1,2-dicarbonitrile Chemical compound CCCCCCCCCCCCSC1=CC=C(SCCCCCCCCCCCC)C(C#N)=C1C#N PKUNOLIHEQYMCI-UHFFFAOYSA-N 0.000 description 4
• UUMCRBQWJBUMCW-UHFFFAOYSA-N 3,6-bis(hexylsulfanyl)benzene-1,2-dicarbonitrile Chemical compound CCCCCCSC1=CC=C(SCCCCCC)C(C#N)=C1C#N UUMCRBQWJBUMCW-UHFFFAOYSA-N 0.000 description 4
• 239000004215 Carbon black (E152) Substances 0.000 description 4
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 4
• UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 4
• UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 4
• DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 4
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
• 238000010521 absorption reaction Methods 0.000 description 4
• 239000007864 aqueous solution Substances 0.000 description 4
• 150000001502 aryl halides Chemical class 0.000 description 4
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
• 230000006399 behavior Effects 0.000 description 4
• UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 4
• 229910052791 calcium Inorganic materials 0.000 description 4
• 230000005292 diamagnetic effect Effects 0.000 description 4
• YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 4
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 4
• WNAHIZMDSQCWRP-UHFFFAOYSA-N dodecane-1-thiol Chemical compound CCCCCCCCCCCCS WNAHIZMDSQCWRP-UHFFFAOYSA-N 0.000 description 4
• 230000008030 elimination Effects 0.000 description 4
• 238000003379 elimination reaction Methods 0.000 description 4
• 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 4
• 229930195733 hydrocarbon Natural products 0.000 description 4
• 150000002430 hydrocarbons Chemical class 0.000 description 4
• 229910052742 iron Inorganic materials 0.000 description 4
• 239000007788 liquid Substances 0.000 description 4
• QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 4
• 150000002736 metal compounds Chemical class 0.000 description 4
• 150000002825 nitriles Chemical class 0.000 description 4
• 239000002953 phosphate buffered saline Substances 0.000 description 4
• 238000012746 preparative thin layer chromatography Methods 0.000 description 4
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
• 238000010626 work up procedure Methods 0.000 description 4
• VNDYJBBGRKZCSX-UHFFFAOYSA-L zinc bromide Chemical compound Br[Zn]Br VNDYJBBGRKZCSX-UHFFFAOYSA-L 0.000 description 4
• NLLGFYPSWCMUIV-UHFFFAOYSA-N (3-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC(B(O)O)=C1 NLLGFYPSWCMUIV-UHFFFAOYSA-N 0.000 description 3
• VOAAEKKFGLPLLU-UHFFFAOYSA-N (4-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=C1 VOAAEKKFGLPLLU-UHFFFAOYSA-N 0.000 description 3
• SNKAWJBJQDLSFF-NVKMUCNASA-N 1,2-dioleoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC SNKAWJBJQDLSFF-NVKMUCNASA-N 0.000 description 3
• DRLUTAGZMJJXGQ-UHFFFAOYSA-N 3,6-bis(3-methoxyphenyl)benzene-1,2-dicarbonitrile Chemical compound COC1=CC=CC(C=2C(=C(C#N)C(C=3C=C(OC)C=CC=3)=CC=2)C#N)=C1 DRLUTAGZMJJXGQ-UHFFFAOYSA-N 0.000 description 3
• BMYRXJQPTUJNCF-UHFFFAOYSA-N 3,6-bis(4-chlorobutyl)benzene-1,2-dicarbonitrile Chemical compound ClCCCCC1=CC=C(CCCCCl)C(C#N)=C1C#N BMYRXJQPTUJNCF-UHFFFAOYSA-N 0.000 description 3
• PUUJFDXHWZXBLV-UHFFFAOYSA-N 3,6-bis(6-chlorohexyl)benzene-1,2-dicarbonitrile Chemical compound ClCCCCCCC1=CC=C(CCCCCCCl)C(C#N)=C1C#N PUUJFDXHWZXBLV-UHFFFAOYSA-N 0.000 description 3
• HLWHEMMJDQNAPJ-UHFFFAOYSA-N 3,6-bis(decylsulfanyl)benzene-1,2-dicarbonitrile Chemical compound CCCCCCCCCCSC1=CC=C(SCCCCCCCCCC)C(C#N)=C1C#N HLWHEMMJDQNAPJ-UHFFFAOYSA-N 0.000 description 3
• GLTAPYYPPPWROQ-UHFFFAOYSA-N 3,6-dibutoxy-4,5-diphenylbenzene-1,2-dicarbonitrile Chemical compound C=1C=CC=CC=1C=1C(OCCCC)=C(C#N)C(C#N)=C(OCCCC)C=1C1=CC=CC=C1 GLTAPYYPPPWROQ-UHFFFAOYSA-N 0.000 description 3
• ZLPCKQYOZCZIKL-UHFFFAOYSA-N 3,6-dibutoxy-4-phenylbenzene-1,2-dicarbonitrile Chemical compound N#CC1=C(C#N)C(OCCCC)=CC(C=2C=CC=CC=2)=C1OCCCC ZLPCKQYOZCZIKL-UHFFFAOYSA-N 0.000 description 3
• CMWOPHRVYNICBF-UHFFFAOYSA-N 3,6-dibutoxy-4-thiophen-2-ylbenzene-1,2-dicarbonitrile Chemical compound N#CC1=C(C#N)C(OCCCC)=CC(C=2SC=CC=2)=C1OCCCC CMWOPHRVYNICBF-UHFFFAOYSA-N 0.000 description 3
• KGYBWMZQDGCJSE-UHFFFAOYSA-N 4-(4-aminophenyl)-3,6-dibutoxybenzene-1,2-dicarbonitrile Chemical compound N#CC1=C(C#N)C(OCCCC)=CC(C=2C=CC(N)=CC=2)=C1OCCCC KGYBWMZQDGCJSE-UHFFFAOYSA-N 0.000 description 3
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 3
• GYHNNYVSQQEPJS-UHFFFAOYSA-N Gallium Chemical compound [Ga] GYHNNYVSQQEPJS-UHFFFAOYSA-N 0.000 description 3
• 101000738322 Homo sapiens Prothymosin alpha Proteins 0.000 description 3
• QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 3
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 3
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
• 238000006069 Suzuki reaction reaction Methods 0.000 description 3
• 102100033632 Tropomyosin alpha-1 chain Human genes 0.000 description 3
• VQFXQNFXFGACHE-UHFFFAOYSA-N [4-(2,5-dibutoxy-3,4-dicyanophenyl)phenyl]methyl methanesulfonate Chemical compound N#CC1=C(C#N)C(OCCCC)=CC(C=2C=CC(COS(C)(=O)=O)=CC=2)=C1OCCCC VQFXQNFXFGACHE-UHFFFAOYSA-N 0.000 description 3
• 125000003277 amino group Chemical group 0.000 description 3
• 238000004458 analytical method Methods 0.000 description 3
• 238000013459 approach Methods 0.000 description 3
• 150000004945 aromatic hydrocarbons Chemical class 0.000 description 3
• 239000012298 atmosphere Substances 0.000 description 3
• KMGBZBJJOKUPIA-UHFFFAOYSA-N butyl iodide Chemical compound CCCCI KMGBZBJJOKUPIA-UHFFFAOYSA-N 0.000 description 3
• XJHCXCQVJFPJIK-UHFFFAOYSA-M cesium fluoride Substances [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 3
• 230000008859 change Effects 0.000 description 3
• IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 3
• 238000004587 chromatography analysis Methods 0.000 description 3
• 229910017052 cobalt Inorganic materials 0.000 description 3
• 239000010941 cobalt Substances 0.000 description 3
• GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 3
• HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 3
• 238000001035 drying Methods 0.000 description 3
• 239000000428 dust Substances 0.000 description 3
• 239000000975 dye Substances 0.000 description 3
• 229920001971 elastomer Polymers 0.000 description 3
• 238000002474 experimental method Methods 0.000 description 3
• 238000002143 fast-atom bombardment mass spectrum Methods 0.000 description 3
• 229910052733 gallium Inorganic materials 0.000 description 3
• 229910052732 germanium Inorganic materials 0.000 description 3
• GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical compound [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 description 3
• 239000012535 impurity Substances 0.000 description 3
• 238000011065 in-situ storage Methods 0.000 description 3
• 229910052738 indium Inorganic materials 0.000 description 3
• APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 3
• 229910052747 lanthanoid Inorganic materials 0.000 description 3
• 150000002602 lanthanoids Chemical class 0.000 description 3
• 239000010410 layer Substances 0.000 description 3
• 239000011133 lead Substances 0.000 description 3
• LTRVAZKHJRYLRJ-UHFFFAOYSA-N lithium;butan-1-olate Chemical compound [Li+].CCCC[O-] LTRVAZKHJRYLRJ-UHFFFAOYSA-N 0.000 description 3
• 238000000816 matrix-assisted laser desorption--ionisation Methods 0.000 description 3
• 229910052753 mercury Inorganic materials 0.000 description 3
• 239000012452 mother liquor Substances 0.000 description 3
• 239000010955 niobium Substances 0.000 description 3
• 229910052758 niobium Inorganic materials 0.000 description 3
• GUCVJGMIXFAOAE-UHFFFAOYSA-N niobium atom Chemical compound [Nb] GUCVJGMIXFAOAE-UHFFFAOYSA-N 0.000 description 3
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
• 230000000144 pharmacologic effect Effects 0.000 description 3
• 150000002989 phenols Chemical class 0.000 description 3
• 230000000886 photobiology Effects 0.000 description 3
• 238000006116 polymerization reaction Methods 0.000 description 3
• TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical class [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 3
• JUJWROOIHBZHMG-RALIUCGRSA-N pyridine-d5 Chemical compound [2H]C1=NC([2H])=C([2H])C([2H])=C1[2H] JUJWROOIHBZHMG-RALIUCGRSA-N 0.000 description 3
• 239000012312 sodium hydride Substances 0.000 description 3
• 229910000104 sodium hydride Inorganic materials 0.000 description 3
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 3
• 239000011135 tin Substances 0.000 description 3
• UYMSTSQPXWFMFR-UHFFFAOYSA-N tridecylborane Chemical compound BCCCCCCCCCCCCC UYMSTSQPXWFMFR-UHFFFAOYSA-N 0.000 description 3
• CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical compound C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 3
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 3
• GPPXJZIENCGNKB-UHFFFAOYSA-N vanadium Chemical compound [V]#[V] GPPXJZIENCGNKB-UHFFFAOYSA-N 0.000 description 3
• XPARCVGSTPKNNR-UHFFFAOYSA-M zinc;ethyl butanoate;bromide Chemical compound [Zn+2].[Br-].CCOC(=O)CC[CH2-] XPARCVGSTPKNNR-UHFFFAOYSA-M 0.000 description 3
• YHHYDZPBBOPWLN-UHFFFAOYSA-N (2,3-dicyanophenyl) trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC1=CC=CC(C#N)=C1C#N YHHYDZPBBOPWLN-UHFFFAOYSA-N 0.000 description 2
• FIRODXFCQOQZSE-UHFFFAOYSA-N (8-bromoquinolin-4-yl)methanol Chemical compound C1=CC=C2C(CO)=CC=NC2=C1Br FIRODXFCQOQZSE-UHFFFAOYSA-N 0.000 description 2
• 125000006649 (C2-C20) alkynyl group Chemical group 0.000 description 2
• APQIUTYORBAGEZ-UHFFFAOYSA-N 1,1-dibromoethane Chemical compound CC(Br)Br APQIUTYORBAGEZ-UHFFFAOYSA-N 0.000 description 2
• PMBXCGGQNSVESQ-UHFFFAOYSA-N 1-Hexanethiol Chemical compound CCCCCCS PMBXCGGQNSVESQ-UHFFFAOYSA-N 0.000 description 2
• 238000005160 1H NMR spectroscopy Methods 0.000 description 2
• VBWZXZKZQWHCOM-UHFFFAOYSA-N 2,5-dibutoxy-4-(2,3-dicyanophenyl)benzoic acid Chemical compound C1=C(C(O)=O)C(OCCCC)=CC(C=2C(=C(C#N)C=CC=2)C#N)=C1OCCCC VBWZXZKZQWHCOM-UHFFFAOYSA-N 0.000 description 2
• XGLVDUUYFKXKPL-UHFFFAOYSA-N 2-(2-methoxyethoxy)-n,n-bis[2-(2-methoxyethoxy)ethyl]ethanamine Chemical compound COCCOCCN(CCOCCOC)CCOCCOC XGLVDUUYFKXKPL-UHFFFAOYSA-N 0.000 description 2
• IQHSSYROJYPFDV-UHFFFAOYSA-N 2-bromo-1,3-dichloro-5-(trifluoromethyl)benzene Chemical group FC(F)(F)C1=CC(Cl)=C(Br)C(Cl)=C1 IQHSSYROJYPFDV-UHFFFAOYSA-N 0.000 description 2
• XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 2
• HELXNKJXGBWXDN-UHFFFAOYSA-N 3,6-bis[4-[tert-butyl(dimethyl)silyl]oxybutyl]benzene-1,2-dicarbonitrile Chemical compound CC(C)(C)[Si](C)(C)OCCCCC1=CC=C(CCCCO[Si](C)(C)C(C)(C)C)C(C#N)=C1C#N HELXNKJXGBWXDN-UHFFFAOYSA-N 0.000 description 2
• VIWINWVCKDNVIZ-UHFFFAOYSA-N 3,6-di(piperidin-1-yl)benzene-1,2-dicarbonitrile Chemical compound N#CC=1C(C#N)=C(N2CCCCC2)C=CC=1N1CCCCC1 VIWINWVCKDNVIZ-UHFFFAOYSA-N 0.000 description 2
• GXFSEGQRWQOYFV-UHFFFAOYSA-N 3,6-dibutoxy-4-(4-methoxyphenyl)benzene-1,2-dicarbonitrile Chemical compound N#CC1=C(C#N)C(OCCCC)=CC(C=2C=CC(OC)=CC=2)=C1OCCCC GXFSEGQRWQOYFV-UHFFFAOYSA-N 0.000 description 2
• IIBMGBRQXLEZPD-UHFFFAOYSA-N 3,6-dibutoxy-4-[4-(dimethylamino)phenyl]benzene-1,2-dicarbonitrile Chemical compound N#CC1=C(C#N)C(OCCCC)=CC(C=2C=CC(=CC=2)N(C)C)=C1OCCCC IIBMGBRQXLEZPD-UHFFFAOYSA-N 0.000 description 2
• DNIMPKVOFJESNJ-UHFFFAOYSA-N 3,6-dibutoxy-4-pyridin-4-ylbenzene-1,2-dicarbonitrile Chemical compound N#CC1=C(C#N)C(OCCCC)=CC(C=2C=CN=CC=2)=C1OCCCC DNIMPKVOFJESNJ-UHFFFAOYSA-N 0.000 description 2
• RJFAMAFEWDBSLX-UHFFFAOYSA-N 3,6-dibutoxybenzene-1,2-dicarbonitrile Chemical compound CCCCOC1=CC=C(OCCCC)C(C#N)=C1C#N RJFAMAFEWDBSLX-UHFFFAOYSA-N 0.000 description 2
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
• FAOJEIKFLZQLBH-UHFFFAOYSA-N 7-iodo-2,2-dimethylheptan-3-one Chemical compound CC(C)(C)C(=O)CCCCI FAOJEIKFLZQLBH-UHFFFAOYSA-N 0.000 description 2
• 102100024321 Alkaline phosphatase, placental type Human genes 0.000 description 2
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
• KLYCPFXDDDMZNQ-UHFFFAOYSA-N Benzyne Chemical compound C1=CC#CC=C1 KLYCPFXDDDMZNQ-UHFFFAOYSA-N 0.000 description 2
• ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
• 206010017533 Fungal infection Diseases 0.000 description 2
• 238000007341 Heck reaction Methods 0.000 description 2
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• 238000006411 Negishi coupling reaction Methods 0.000 description 2
• 206010029113 Neovascularisation Diseases 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
• OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 2
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
• 102000004142 Trypsin Human genes 0.000 description 2
• 108090000631 Trypsin Proteins 0.000 description 2
• JKCYUAPVJLZDCT-UHFFFAOYSA-N [2,3-dicyano-4-(1,1,2,2,3,3,4,4,4-nonafluorobutylsulfonyloxy)phenyl] 1,1,2,2,3,3,4,4,4-nonafluorobutane-1-sulfonate Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)S(=O)(=O)OC1=CC=C(OS(=O)(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)C(C#N)=C1C#N JKCYUAPVJLZDCT-UHFFFAOYSA-N 0.000 description 2
• PAVFOQDYFGUYPY-UHFFFAOYSA-M [Br-].ClCCCCCC[Zn+] Chemical compound [Br-].ClCCCCCC[Zn+] PAVFOQDYFGUYPY-UHFFFAOYSA-M 0.000 description 2
• 238000002835 absorbance Methods 0.000 description 2
• CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 2
• 238000007259 addition reaction Methods 0.000 description 2
• 125000003158 alcohol group Chemical group 0.000 description 2
• 125000003545 alkoxy group Chemical group 0.000 description 2
• 125000004414 alkyl thio group Chemical group 0.000 description 2
• 150000001356 alkyl thiols Chemical class 0.000 description 2
• 150000001412 amines Chemical class 0.000 description 2
• 239000007900 aqueous suspension Substances 0.000 description 2
• 150000001499 aryl bromides Chemical class 0.000 description 2
• 150000001500 aryl chlorides Chemical class 0.000 description 2
• 150000001503 aryl iodides Chemical class 0.000 description 2
• 239000008280 blood Substances 0.000 description 2
• 210000004369 blood Anatomy 0.000 description 2
• 230000037396 body weight Effects 0.000 description 2
• 229910000085 borane Inorganic materials 0.000 description 2
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
• 230000031709 bromination Effects 0.000 description 2
• 238000005893 bromination reaction Methods 0.000 description 2
• 239000006227 byproduct Substances 0.000 description 2
• 239000001569 carbon dioxide Substances 0.000 description 2
• 229910002092 carbon dioxide Inorganic materials 0.000 description 2
• 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 2
• 239000012876 carrier material Substances 0.000 description 2
• 238000005352 clarification Methods 0.000 description 2
• 238000004040 coloring Methods 0.000 description 2
• 239000012230 colorless oil Substances 0.000 description 2
• 229920001577 copolymer Polymers 0.000 description 2
• 239000013058 crude material Substances 0.000 description 2
• 239000002178 crystalline material Substances 0.000 description 2
• 125000004122 cyclic group Chemical class 0.000 description 2
• 229940127089 cytotoxic agent Drugs 0.000 description 2
• 239000002254 cytotoxic agent Substances 0.000 description 2
• 231100000599 cytotoxic agent Toxicity 0.000 description 2
• 238000013500 data storage Methods 0.000 description 2
• VTXVGVNLYGSIAR-UHFFFAOYSA-N decane-1-thiol Chemical compound CCCCCCCCCCS VTXVGVNLYGSIAR-UHFFFAOYSA-N 0.000 description 2
• 239000006185 dispersion Substances 0.000 description 2
• 238000000921 elemental analysis Methods 0.000 description 2
• YWFGJRGXFPIQDZ-UHFFFAOYSA-N ethyl 4-(2,5-dibutoxy-3,4-dicyanophenyl)butanoate Chemical compound CCCCOC1=CC(CCCC(=O)OCC)=C(OCCCC)C(C#N)=C1C#N YWFGJRGXFPIQDZ-UHFFFAOYSA-N 0.000 description 2
• IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 2
• 230000005284 excitation Effects 0.000 description 2
• 239000000284 extract Substances 0.000 description 2
• 239000012065 filter cake Substances 0.000 description 2
• 208000024386 fungal infectious disease Diseases 0.000 description 2
• 238000004817 gas chromatography Methods 0.000 description 2
• 239000011521 glass Substances 0.000 description 2
• 150000004795 grignard reagents Chemical class 0.000 description 2
• 230000002140 halogenating effect Effects 0.000 description 2
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
• 125000005113 hydroxyalkoxy group Chemical group 0.000 description 2
• 125000002768 hydroxyalkyl group Chemical group 0.000 description 2
• 238000011534 incubation Methods 0.000 description 2
• APHGZSBLRQFRCA-UHFFFAOYSA-M indium(1+);chloride Chemical compound [In]Cl APHGZSBLRQFRCA-UHFFFAOYSA-M 0.000 description 2
• PSCMQHVBLHHWTO-UHFFFAOYSA-K indium(iii) chloride Chemical compound Cl[In](Cl)Cl PSCMQHVBLHHWTO-UHFFFAOYSA-K 0.000 description 2
• 238000003780 insertion Methods 0.000 description 2
• 230000037431 insertion Effects 0.000 description 2
• 238000007917 intracranial administration Methods 0.000 description 2
• 238000007918 intramuscular administration Methods 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 229940046892 lead acetate Drugs 0.000 description 2
• 238000005259 measurement Methods 0.000 description 2
• 230000007246 mechanism Effects 0.000 description 2
• 230000001404 mediated effect Effects 0.000 description 2
• 238000005649 metathesis reaction Methods 0.000 description 2
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
• 239000000178 monomer Substances 0.000 description 2
• BMGNSKKZFQMGDH-FDGPNNRMSA-L nickel(2+);(z)-4-oxopent-2-en-2-olate Chemical compound [Ni+2].C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O BMGNSKKZFQMGDH-FDGPNNRMSA-L 0.000 description 2
• HIIGGQNLPWIVAG-UHFFFAOYSA-L nickel(2+);diacetate;hydrate Chemical compound O.[Ni+2].CC([O-])=O.CC([O-])=O HIIGGQNLPWIVAG-UHFFFAOYSA-L 0.000 description 2
• 238000007339 nucleophilic aromatic substitution reaction Methods 0.000 description 2
• 150000002894 organic compounds Chemical class 0.000 description 2
• 150000002940 palladium Chemical class 0.000 description 2
• 238000010651 palladium-catalyzed cross coupling reaction Methods 0.000 description 2
• 230000001575 pathological effect Effects 0.000 description 2
• 239000008188 pellet Substances 0.000 description 2
• LUYQYZLEHLTPBH-UHFFFAOYSA-N perfluorobutanesulfonyl fluoride Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)S(F)(=O)=O LUYQYZLEHLTPBH-UHFFFAOYSA-N 0.000 description 2
• 208000017983 photosensitivity disease Diseases 0.000 description 2
• 231100000434 photosensitization Toxicity 0.000 description 2
• 230000000704 physical effect Effects 0.000 description 2
• IVDFJHOHABJVEH-UHFFFAOYSA-N pinacol Chemical compound CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 description 2
• 108010031345 placental alkaline phosphatase Proteins 0.000 description 2
• 229920000728 polyester Polymers 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
• 238000011160 research Methods 0.000 description 2
• 239000004065 semiconductor Substances 0.000 description 2
• 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 2
• 238000010532 solid phase synthesis reaction Methods 0.000 description 2
• 239000011877 solvent mixture Substances 0.000 description 2
• 238000003860 storage Methods 0.000 description 2
• UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 229910052717 sulfur Chemical group 0.000 description 2
• 230000009885 systemic effect Effects 0.000 description 2
• 238000012360 testing method Methods 0.000 description 2
• 239000010409 thin film Substances 0.000 description 2
• ARYHTUPFQTUBBG-UHFFFAOYSA-N thiophen-2-ylboronic acid Chemical compound OB(O)C1=CC=CS1 ARYHTUPFQTUBBG-UHFFFAOYSA-N 0.000 description 2
• 229930192474 thiophene Natural products 0.000 description 2
• 230000000699 topical effect Effects 0.000 description 2
• 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 2
• 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 2
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• 239000012588 trypsin Substances 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
• 150000003751 zinc Chemical class 0.000 description 2
• 229940102001 zinc bromide Drugs 0.000 description 2
• XRILZZJFFXPAEL-UHFFFAOYSA-N (2,3-dicyano-4-decylphenyl) trifluoromethanesulfonate Chemical compound CCCCCCCCCCC1=CC=C(OS(=O)(=O)C(F)(F)F)C(C#N)=C1C#N XRILZZJFFXPAEL-UHFFFAOYSA-N 0.000 description 1
• MKPDAJWEBQRQCO-UHFFFAOYSA-N (4-aminophenyl)boronic acid Chemical compound NC1=CC=C(B(O)O)C=C1 MKPDAJWEBQRQCO-UHFFFAOYSA-N 0.000 description 1
• WHXSMMKQMYFTQS-BJUDXGSMSA-N (6Li)Lithium Chemical compound [6Li] WHXSMMKQMYFTQS-BJUDXGSMSA-N 0.000 description 1
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
• YYOGYQNNOGKIFI-UHFFFAOYSA-N 1,4-bis(3-methoxyphenyl)cyclohexa-3,5-diene-1,2-dicarbonitrile Chemical compound COC1=CC=CC(C=2C=CC(C(C#N)C=2)(C#N)C=2C=C(OC)C=CC=2)=C1 YYOGYQNNOGKIFI-UHFFFAOYSA-N 0.000 description 1
• JJBQXTABLSZHGC-UHFFFAOYSA-N 1,4-dihydroxynaphthalene-2,3-dicarbonitrile Chemical compound C1=CC=C2C(O)=C(C#N)C(C#N)=C(O)C2=C1 JJBQXTABLSZHGC-UHFFFAOYSA-N 0.000 description 1
• XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 1
• JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
• ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 description 1
• REFDOIWRJDGBHY-UHFFFAOYSA-N 2-bromobenzene-1,4-diol Chemical compound OC1=CC=C(O)C(Br)=C1 REFDOIWRJDGBHY-UHFFFAOYSA-N 0.000 description 1
• PYEQXZOIQJWYAH-UHFFFAOYSA-N 2-bromocyclohexa-2,5-diene-1,4-dione Chemical compound BrC1=CC(=O)C=CC1=O PYEQXZOIQJWYAH-UHFFFAOYSA-N 0.000 description 1
• CCZWSTFVHJPCEM-UHFFFAOYSA-N 2-iodopyridine Chemical compound IC1=CC=CC=N1 CCZWSTFVHJPCEM-UHFFFAOYSA-N 0.000 description 1
• CEBKHWWANWSNTI-UHFFFAOYSA-N 2-methylbut-3-yn-2-ol Chemical compound CC(C)(O)C#C CEBKHWWANWSNTI-UHFFFAOYSA-N 0.000 description 1
• CFIYISMWOOTOLG-UHFFFAOYSA-N 3,6-bis(6,6-dimethyl-5-oxoheptyl)benzene-1,2-dicarbonitrile Chemical compound CC(C)(C)C(=O)CCCCC1=CC=C(CCCCC(=O)C(C)(C)C)C(C#N)=C1C#N CFIYISMWOOTOLG-UHFFFAOYSA-N 0.000 description 1
• GOPNQBNDBLKOGZ-UHFFFAOYSA-N 3,6-bis(heptylsulfanyl)benzene-1,2-dicarbonitrile Chemical compound CCCCCCCSC1=CC=C(SCCCCCCC)C(C#N)=C1C#N GOPNQBNDBLKOGZ-UHFFFAOYSA-N 0.000 description 1
• VMNBVZXPKRYDHE-UHFFFAOYSA-N 3,6-bis(nonylsulfanyl)benzene-1,2-dicarbonitrile Chemical compound CCCCCCCCCSC1=CC=C(SCCCCCCCCC)C(C#N)=C1C#N VMNBVZXPKRYDHE-UHFFFAOYSA-N 0.000 description 1
• YPFCPDDBDOIGHD-UHFFFAOYSA-N 3,6-bis(octylsulfanyl)benzene-1,2-dicarbonitrile Chemical compound CCCCCCCCSC1=CC=C(SCCCCCCCC)C(C#N)=C1C#N YPFCPDDBDOIGHD-UHFFFAOYSA-N 0.000 description 1
• ZEPIONWMIXGQDP-UHFFFAOYSA-N 3,6-bis(undecylsulfanyl)benzene-1,2-dicarbonitrile Chemical compound CCCCCCCCCCCSC1=CC=C(SCCCCCCCCCCC)C(C#N)=C1C#N ZEPIONWMIXGQDP-UHFFFAOYSA-N 0.000 description 1
• APUOFYQGISEQAA-UHFFFAOYSA-N 3,6-dibutoxy-4-(4-oxohexyl)benzene-1,2-dicarbonitrile Chemical compound CCCCOC1=CC(CCCC(=O)CC)=C(OCCCC)C(C#N)=C1C#N APUOFYQGISEQAA-UHFFFAOYSA-N 0.000 description 1
• JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 1
• SWBMSIBEMDFILF-UHFFFAOYSA-N 3-butan-2-yloxybenzene-1,2-dicarbonitrile Chemical compound CCC(C)OC1=CC=CC(C#N)=C1C#N SWBMSIBEMDFILF-UHFFFAOYSA-N 0.000 description 1
• OYPIAMMBWHEBHP-UHFFFAOYSA-N 4-(2,5-dibutoxy-3,4-dicyanophenyl)benzoic acid Chemical compound N#CC1=C(C#N)C(OCCCC)=CC(C=2C=CC(=CC=2)C(O)=O)=C1OCCCC OYPIAMMBWHEBHP-UHFFFAOYSA-N 0.000 description 1
• NLTIETZTDSJANS-UHFFFAOYSA-N 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=NC=C1 NLTIETZTDSJANS-UHFFFAOYSA-N 0.000 description 1
• DFKKJQABUJCNLE-UHFFFAOYSA-N 4-(hydrazinylmethyl)phenol Chemical compound NNCC1=CC=C(O)C=C1 DFKKJQABUJCNLE-UHFFFAOYSA-N 0.000 description 1
• XEUXQSZILBIIEJ-UHFFFAOYSA-N 4-[2,3-dicyano-4-[4-(2,2-dimethylpropanoyloxy)butyl]phenyl]butyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCCCC1=CC=C(CCCCOC(=O)C(C)(C)C)C(C#N)=C1C#N XEUXQSZILBIIEJ-UHFFFAOYSA-N 0.000 description 1
• SIAVMDKGVRXFAX-UHFFFAOYSA-N 4-carboxyphenylboronic acid Chemical compound OB(O)C1=CC=C(C(O)=O)C=C1 SIAVMDKGVRXFAX-UHFFFAOYSA-N 0.000 description 1
• RTLUPHDWSUGAOS-UHFFFAOYSA-N 4-iodopyridine Chemical compound IC1=CC=NC=C1 RTLUPHDWSUGAOS-UHFFFAOYSA-N 0.000 description 1
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
• 101100129007 Arabidopsis thaliana LTD gene Proteins 0.000 description 1
• 241001120493 Arene Species 0.000 description 1
• JBRZTFJDHDCESZ-UHFFFAOYSA-N AsGa Chemical compound [As]#[Ga] JBRZTFJDHDCESZ-UHFFFAOYSA-N 0.000 description 1
• 208000035143 Bacterial infection Diseases 0.000 description 1
• BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
• 241000167854 Bourreria succulenta Species 0.000 description 1
• HEPSLFGQJSHKLJ-UHFFFAOYSA-N C(CCCCCCCCC)C1=C(C(C#N)=CC(=C1)CCCCCCCCCC)C#N Chemical compound C(CCCCCCCCC)C1=C(C(C#N)=CC(=C1)CCCCCCCCCC)C#N HEPSLFGQJSHKLJ-UHFFFAOYSA-N 0.000 description 1
• JAZGGNIVSIGGBU-UHFFFAOYSA-N C(CCCCCCCCC)C1=C(C(C#N)=CC=C1)C#N Chemical compound C(CCCCCCCCC)C1=C(C(C#N)=CC=C1)C#N JAZGGNIVSIGGBU-UHFFFAOYSA-N 0.000 description 1
• 125000006374 C2-C10 alkenyl group Chemical group 0.000 description 1
• 125000006416 CBr Chemical group BrC* 0.000 description 1
• QAEGJXBKLGGWKA-UHFFFAOYSA-N CC(C)(C)[Si](C)(C)OCCCCc1cccc(C#N)c1C#N Chemical compound CC(C)(C)[Si](C)(C)OCCCCc1cccc(C#N)c1C#N QAEGJXBKLGGWKA-UHFFFAOYSA-N 0.000 description 1
• PBEHMIMZBVHCBF-UHFFFAOYSA-N CCCCCCCCCCCCCCCCCC[Zn] Chemical compound CCCCCCCCCCCCCCCCCC[Zn] PBEHMIMZBVHCBF-UHFFFAOYSA-N 0.000 description 1
• 241000819038 Chichester Species 0.000 description 1
• 238000005698 Diels-Alder reaction Methods 0.000 description 1
• 241001050985 Disco Species 0.000 description 1
• 101100289061 Drosophila melanogaster lili gene Proteins 0.000 description 1
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
• 201000008808 Fibrosarcoma Diseases 0.000 description 1
• KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
• 241000233866 Fungi Species 0.000 description 1
• 229910001218 Gallium arsenide Inorganic materials 0.000 description 1
• 102000006395 Globulins Human genes 0.000 description 1
• 108010044091 Globulins Proteins 0.000 description 1
• 239000007818 Grignard reagent Substances 0.000 description 1
• GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 1
• 229910021617 Indium monochloride Inorganic materials 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
• 238000005684 Liebig rearrangement reaction Methods 0.000 description 1
• JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
• 241001465754 Metazoa Species 0.000 description 1
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
• 238000006751 Mitsunobu reaction Methods 0.000 description 1
• 101100505385 Mus musculus Gpd1 gene Proteins 0.000 description 1
• 208000031888 Mycoses Diseases 0.000 description 1
• GOTYPHJYOIRENG-QRPNPIFTSA-N OBO.OC(=O)[C@@H](N)CC1=CC=CC=C1 Chemical class OBO.OC(=O)[C@@H](N)CC1=CC=CC=C1 GOTYPHJYOIRENG-QRPNPIFTSA-N 0.000 description 1
• 229930182555 Penicillin Natural products 0.000 description 1
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 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
• 229920002732 Polyanhydride Polymers 0.000 description 1
• 229920001710 Polyorthoester Polymers 0.000 description 1
• 239000004793 Polystyrene Substances 0.000 description 1
• 206010039491 Sarcoma Diseases 0.000 description 1
• 229910004219 SiNi Inorganic materials 0.000 description 1
• 229910004298 SiO 2 Inorganic materials 0.000 description 1
• 239000004990 Smectic liquid crystal Substances 0.000 description 1
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
• 229910000831 Steel Inorganic materials 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• 238000006959 Williamson synthesis reaction Methods 0.000 description 1
• MZLTWBHTTDHCAV-UHFFFAOYSA-N [2,3-dicyano-4-(trifluoromethylsulfonyloxy)naphthalen-1-yl] trifluoromethanesulfonate Chemical compound C1=CC=C2C(OS(=O)(=O)C(F)(F)F)=C(C#N)C(C#N)=C(OS(=O)(=O)C(F)(F)F)C2=C1 MZLTWBHTTDHCAV-UHFFFAOYSA-N 0.000 description 1
• PZRPBPMLSSNFOM-UHFFFAOYSA-N [4-(hydroxymethyl)phenyl]boronic acid Chemical compound OCC1=CC=C(B(O)O)C=C1 PZRPBPMLSSNFOM-UHFFFAOYSA-N 0.000 description 1
• YDPVAYXEHNRIKW-UHFFFAOYSA-M [Br-].ClCCCC[Zn+] Chemical compound [Br-].ClCCCC[Zn+] YDPVAYXEHNRIKW-UHFFFAOYSA-M 0.000 description 1
• CKCYDFVZAPRMBQ-UHFFFAOYSA-M [Cl-].CCCCCCCCCC[Mg+] Chemical compound [Cl-].CCCCCCCCCC[Mg+] CKCYDFVZAPRMBQ-UHFFFAOYSA-M 0.000 description 1
• IYRNUFOFIFCJLO-UHFFFAOYSA-M [Cl-].CCCCCCCCCC[Zn+] Chemical compound [Cl-].CCCCCCCCCC[Zn+] IYRNUFOFIFCJLO-UHFFFAOYSA-M 0.000 description 1
• 150000001241 acetals Chemical class 0.000 description 1
• MQRWBMAEBQOWAF-UHFFFAOYSA-N acetic acid;nickel Chemical compound [Ni].CC(O)=O.CC(O)=O MQRWBMAEBQOWAF-UHFFFAOYSA-N 0.000 description 1
• 238000005903 acid hydrolysis reaction Methods 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 238000011374 additional therapy Methods 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 238000013019 agitation Methods 0.000 description 1
• 150000001345 alkine derivatives Chemical class 0.000 description 1
• 150000001347 alkyl bromides Chemical class 0.000 description 1
• 150000001351 alkyl iodides Chemical class 0.000 description 1
• 125000003368 amide group Chemical group 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 150000003862 amino acid derivatives Chemical class 0.000 description 1
• 235000019270 ammonium chloride Nutrition 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 150000001454 anthracenes Chemical class 0.000 description 1
• 239000011260 aqueous acid Substances 0.000 description 1
• 239000006286 aqueous extract Substances 0.000 description 1
• 239000003637 basic solution Substances 0.000 description 1
• 239000011324 bead Substances 0.000 description 1
• UHOVQNZJYSORNB-MZWXYZOWSA-N benzene-d6 Chemical compound [2H]C1=C([2H])C([2H])=C([2H])C([2H])=C1[2H] UHOVQNZJYSORNB-MZWXYZOWSA-N 0.000 description 1
• 150000001555 benzenes Chemical class 0.000 description 1
• AFYNADDZULBEJA-UHFFFAOYSA-N bicinchoninic acid Chemical compound C1=CC=CC2=NC(C=3C=C(C4=CC=CC=C4N=3)C(=O)O)=CC(C(O)=O)=C21 AFYNADDZULBEJA-UHFFFAOYSA-N 0.000 description 1
• 238000003236 bicinchoninic acid assay Methods 0.000 description 1
• 229920002988 biodegradable polymer Polymers 0.000 description 1
• 239000004621 biodegradable polymer Substances 0.000 description 1
• SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
• 229920001400 block copolymer Polymers 0.000 description 1
• 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
• 229910001424 calcium ion Inorganic materials 0.000 description 1
• 244000309466 calf Species 0.000 description 1
• 238000011088 calibration curve Methods 0.000 description 1
• 229910002091 carbon monoxide Inorganic materials 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 230000022131 cell cycle Effects 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• 229920005556 chlorobutyl Polymers 0.000 description 1
• 229960004407 chorionic gonadotrophin Drugs 0.000 description 1
• 238000013375 chromatographic separation Methods 0.000 description 1
• 238000011097 chromatography purification Methods 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 239000002131 composite material Substances 0.000 description 1
• 239000004020 conductor Substances 0.000 description 1
• 238000012790 confirmation Methods 0.000 description 1
• 239000006184 cosolvent Substances 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 239000010779 crude oil Substances 0.000 description 1
• 229910021419 crystalline silicon Inorganic materials 0.000 description 1
• NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 1
• 231100000433 cytotoxic Toxicity 0.000 description 1
• 230000001472 cytotoxic effect Effects 0.000 description 1
• 230000003013 cytotoxicity Effects 0.000 description 1
• 231100000135 cytotoxicity Toxicity 0.000 description 1
• 230000009849 deactivation Effects 0.000 description 1
• 238000010908 decantation Methods 0.000 description 1
• 238000000354 decomposition reaction Methods 0.000 description 1
• 230000017858 demethylation Effects 0.000 description 1
• 238000010520 demethylation reaction Methods 0.000 description 1
• 229940039227 diagnostic agent Drugs 0.000 description 1
• 239000000032 diagnostic agent Substances 0.000 description 1
• WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 1
• 239000002027 dichloromethane extract Substances 0.000 description 1
• 150000005690 diesters Chemical class 0.000 description 1
• 238000007865 diluting Methods 0.000 description 1
• ALKZAGKDWUSJED-UHFFFAOYSA-N dinuclear copper ion Chemical compound [Cu].[Cu] ALKZAGKDWUSJED-UHFFFAOYSA-N 0.000 description 1
• YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
• 238000010494 dissociation reaction Methods 0.000 description 1
• 230000005593 dissociations Effects 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 238000012377 drug delivery Methods 0.000 description 1
• 238000010828 elution Methods 0.000 description 1
• 125000004185 ester group Chemical group 0.000 description 1
• GSFZBNQNAIJHGO-UHFFFAOYSA-N ethyl 4-[2,3-dicyano-4-(4-ethoxy-4-oxobutyl)phenyl]butanoate Chemical compound CCOC(=O)CCCC1=CC=C(CCCC(=O)OCC)C(C#N)=C1C#N GSFZBNQNAIJHGO-UHFFFAOYSA-N 0.000 description 1
• FMVJYQGSRWVMQV-UHFFFAOYSA-N ethyl propiolate Chemical compound CCOC(=O)C#C FMVJYQGSRWVMQV-UHFFFAOYSA-N 0.000 description 1
• 230000001605 fetal effect Effects 0.000 description 1
• 238000011010 flushing procedure Methods 0.000 description 1
• 239000011888 foil Substances 0.000 description 1
• 230000006870 function Effects 0.000 description 1
• 238000007429 general method Methods 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• 239000001963 growth medium Substances 0.000 description 1
• 229910052736 halogen Inorganic materials 0.000 description 1
• 125000005842 heteroatom Chemical group 0.000 description 1
• GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
• 235000020256 human milk Nutrition 0.000 description 1
• 210000004251 human milk Anatomy 0.000 description 1
• 238000006197 hydroboration reaction Methods 0.000 description 1
• 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
• 230000003301 hydrolyzing effect Effects 0.000 description 1
• 239000012052 hydrophilic carrier Substances 0.000 description 1
• 230000002209 hydrophobic effect Effects 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 238000001727 in vivo Methods 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 239000003041 laboratory chemical Substances 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 239000004973 liquid crystal related substance Substances 0.000 description 1
• 231100000053 low toxicity Toxicity 0.000 description 1
• 229920002521 macromolecule Polymers 0.000 description 1
• 229910001629 magnesium chloride Inorganic materials 0.000 description 1
• 229910001425 magnesium ion Inorganic materials 0.000 description 1
• NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 238000001254 matrix assisted laser desorption--ionisation time-of-flight mass spectrum Methods 0.000 description 1
• 230000015654 memory Effects 0.000 description 1
• 238000003328 mesylation reaction Methods 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 229910021645 metal ion Inorganic materials 0.000 description 1
• 229920003240 metallophthalocyanine polymer Polymers 0.000 description 1
• 150000002739 metals Chemical class 0.000 description 1
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
• 239000002032 methanolic fraction Substances 0.000 description 1
• WJYBMWHJTZBYSO-UHFFFAOYSA-N methyl 3-bromobutanoate Chemical compound COC(=O)CC(C)Br WJYBMWHJTZBYSO-UHFFFAOYSA-N 0.000 description 1
• MWZPENIJLUWBSY-VIFPVBQESA-N methyl L-tyrosinate Chemical compound COC(=O)[C@@H](N)CC1=CC=C(O)C=C1 MWZPENIJLUWBSY-VIFPVBQESA-N 0.000 description 1
• 244000005700 microbiome Species 0.000 description 1
• 238000000386 microscopy Methods 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
• HQFYIDOMCULPIW-UHFFFAOYSA-N n-methylprop-2-yn-1-amine Chemical compound CNCC#C HQFYIDOMCULPIW-UHFFFAOYSA-N 0.000 description 1
• 150000002790 naphthalenes Chemical class 0.000 description 1
• 150000002815 nickel Chemical class 0.000 description 1
• 229940078494 nickel acetate Drugs 0.000 description 1
• 229940078487 nickel acetate tetrahydrate Drugs 0.000 description 1
• OINIXPNQKAZCRL-UHFFFAOYSA-L nickel(2+);diacetate;tetrahydrate Chemical compound O.O.O.O.[Ni+2].CC([O-])=O.CC([O-])=O OINIXPNQKAZCRL-UHFFFAOYSA-L 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• 125000005151 nonafluorobutanesulfonyl group Chemical group FC(C(C(S(=O)(=O)*)(F)F)(F)F)(C(F)(F)F)F 0.000 description 1
• 238000010899 nucleation Methods 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 239000012074 organic phase Substances 0.000 description 1
• 150000002900 organolithium compounds Chemical class 0.000 description 1
• 125000001979 organolithium group Chemical group 0.000 description 1
• 239000007800 oxidant agent Substances 0.000 description 1
• 150000002926 oxygen Chemical class 0.000 description 1
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
• 230000005298 paramagnetic effect Effects 0.000 description 1
• 230000000149 penetrating effect Effects 0.000 description 1
• 230000035515 penetration Effects 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• 150000002987 phenanthrenes Chemical class 0.000 description 1
• COLNVLDHVKWLRT-QMMMGPOBSA-N phenylalanine group Chemical group N[C@@H](CC1=CC=CC=C1)C(=O)O COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
• 150000003904 phospholipids Chemical class 0.000 description 1
• DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
• 238000006552 photochemical reaction Methods 0.000 description 1
• 230000002165 photosensitisation Effects 0.000 description 1
• 238000001126 phototherapy Methods 0.000 description 1
• 231100000760 phototoxic Toxicity 0.000 description 1
• 238000001907 polarising light microscopy Methods 0.000 description 1
• 230000010287 polarization Effects 0.000 description 1
• 229920002627 poly(phosphazenes) Polymers 0.000 description 1
• 229920002223 polystyrene Polymers 0.000 description 1
• 150000004032 porphyrins Chemical class 0.000 description 1
• 229910000160 potassium phosphate Inorganic materials 0.000 description 1
• 235000011009 potassium phosphates Nutrition 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 238000006862 quantum yield reaction Methods 0.000 description 1
• 230000035484 reaction time Effects 0.000 description 1
• 230000009257 reactivity Effects 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 235000009518 sodium iodide Nutrition 0.000 description 1
• 239000007790 solid phase Substances 0.000 description 1
• 239000012265 solid product Substances 0.000 description 1
• 238000002798 spectrophotometry method Methods 0.000 description 1
• 238000010186 staining Methods 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 239000010959 steel Substances 0.000 description 1
• 239000011550 stock solution Substances 0.000 description 1
• 229960005322 streptomycin Drugs 0.000 description 1
• 239000011593 sulfur Chemical group 0.000 description 1
• INGJYKISFRSCQV-UHFFFAOYSA-N tert-butyl-(4-iodobutoxy)-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OCCCCI INGJYKISFRSCQV-UHFFFAOYSA-N 0.000 description 1
• DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• UMHFSEWKWORSLP-UHFFFAOYSA-N thiophene 1,1-dioxide Chemical compound O=S1(=O)C=CC=C1 UMHFSEWKWORSLP-UHFFFAOYSA-N 0.000 description 1
• 238000005809 transesterification reaction Methods 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 238000006478 transmetalation reaction Methods 0.000 description 1
• 239000012780 transparent material Substances 0.000 description 1
• YEMJHNYABQHWHL-UHFFFAOYSA-N tributyl(ethynyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C#C YEMJHNYABQHWHL-UHFFFAOYSA-N 0.000 description 1
• 125000002889 tridecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
• BPLUKJNHPBNVQL-UHFFFAOYSA-N triphenylarsine Chemical compound C1=CC=CC=C1[As](C=1C=CC=CC=1)C1=CC=CC=C1 BPLUKJNHPBNVQL-UHFFFAOYSA-N 0.000 description 1
• FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
• 229910052721 tungsten Inorganic materials 0.000 description 1
• 239000010937 tungsten Substances 0.000 description 1
• 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1