TWI546303B - 氮雜吲唑（ａｚａｉｎｄａｚｏｌｅ）或二氮雜吲唑（ｄｉａｚａｉｎｄａｚｏｌｅ）類型之衍生物供作藥物之用途 - Google Patents

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Publication number

TWI546303B

TWI546303B TW101102531A TW101102531A TWI546303B TW I546303 B TWI546303 B TW I546303B TW 101102531 A TW101102531 A TW 101102531A TW 101102531 A TW101102531 A TW 101102531A TW I546303 B TWI546303 B TW I546303B

Authority

TW

Taiwan

Prior art keywords

aromatic

compound

group

formula

mmol

Prior art date

2011-01-27

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• 239000003814 drug Substances 0.000 title claims description 12
• VQNDBXJTIJKJPV-UHFFFAOYSA-N 2h-triazolo[4,5-b]pyridine Chemical compound C1=CC=NC2=NNN=C21 VQNDBXJTIJKJPV-UHFFFAOYSA-N 0.000 title 1
• QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical class C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 title 1
• 125000003118 aryl group Chemical group 0.000 claims description 807
• 150000001875 compounds Chemical class 0.000 claims description 185
• 238000000034 method Methods 0.000 claims description 173
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 147
• 229910020008 S(O) Inorganic materials 0.000 claims description 66
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 64
• 239000000203 mixture Substances 0.000 claims description 54
• 229910052757 nitrogen Inorganic materials 0.000 claims description 43
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 39
• 229910052739 hydrogen Inorganic materials 0.000 claims description 36
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 35
• 206010028980 Neoplasm Diseases 0.000 claims description 35
• 239000001257 hydrogen Substances 0.000 claims description 34
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 29
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 27
• 230000008569 process Effects 0.000 claims description 27
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 25
• 150000003839 salts Chemical class 0.000 claims description 25
• 229910052717 sulfur Inorganic materials 0.000 claims description 25
• 239000011593 sulfur Chemical group 0.000 claims description 24
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
• 201000011510 cancer Diseases 0.000 claims description 20
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 18
• 125000000623 heterocyclic group Chemical group 0.000 claims description 18
• 108091000080 Phosphotransferase Proteins 0.000 claims description 17
• 102000020233 phosphotransferase Human genes 0.000 claims description 17
• 238000010511 deprotection reaction Methods 0.000 claims description 16
• 230000000694 effects Effects 0.000 claims description 15
• 238000005859 coupling reaction Methods 0.000 claims description 14
• 125000005843 halogen group Chemical group 0.000 claims description 14
• 238000002360 preparation method Methods 0.000 claims description 13
• 102000001332 SRC Human genes 0.000 claims description 12
• 108060006706 SRC Proteins 0.000 claims description 12
• 239000008194 pharmaceutical composition Substances 0.000 claims description 12
• 125000004076 pyridyl group Chemical group 0.000 claims description 12
• 125000004432 carbon atom Chemical group C* 0.000 claims description 11
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 9
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
• 229910052760 oxygen Inorganic materials 0.000 claims description 9
• 239000001301 oxygen Substances 0.000 claims description 9
• 239000000126 substance Substances 0.000 claims description 9
• 229910052770 Uranium Inorganic materials 0.000 claims description 8
• 239000004480 active ingredient Substances 0.000 claims description 8
• 201000010099 disease Diseases 0.000 claims description 8
• 239000003112 inhibitor Substances 0.000 claims description 8
• 125000001424 substituent group Chemical group 0.000 claims description 8
• 230000004770 neurodegeneration Effects 0.000 claims description 7
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 7
• 239000012453 solvate Substances 0.000 claims description 7
• 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 6
• 208000024827 Alzheimer disease Diseases 0.000 claims description 6
• 239000002246 antineoplastic agent Substances 0.000 claims description 5
• 125000004429 atom Chemical group 0.000 claims description 5
• 238000010168 coupling process Methods 0.000 claims description 5
• 125000001072 heteroaryl group Chemical group 0.000 claims description 5
• 230000008878 coupling Effects 0.000 claims description 4
• 238000006268 reductive amination reaction Methods 0.000 claims description 4
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
• 206010061218 Inflammation Diseases 0.000 claims 1
• 125000004438 haloalkoxy group Chemical group 0.000 claims 1
• 230000004054 inflammatory process Effects 0.000 claims 1
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 265
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 229
• 238000006243 chemical reaction Methods 0.000 description 136
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 132
• 239000000243 solution Substances 0.000 description 122
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 101
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 100
• 235000019439 ethyl acetate Nutrition 0.000 description 86
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 74
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 72
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 72
• -1 Kit Proteins 0.000 description 70
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 68
• 239000002904 solvent Substances 0.000 description 68
• 239000000758 substrate Substances 0.000 description 68
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 63
• 239000007787 solid Substances 0.000 description 62
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 56
• 239000012074 organic phase Substances 0.000 description 56
• 239000011541 reaction mixture Substances 0.000 description 53
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 52
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 51
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 51
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 45
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 40
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 39
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 39
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 39
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 37
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 36
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 36
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 32
• 235000019341 magnesium sulphate Nutrition 0.000 description 32
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 31
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical class [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 28
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 26
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 25
• 239000000047 product Substances 0.000 description 24
• 239000002798 polar solvent Substances 0.000 description 23
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 22
• 230000015572 biosynthetic process Effects 0.000 description 22
• 102100033793 ALK tyrosine kinase receptor Human genes 0.000 description 21
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 21
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 21
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 20
• 101000779641 Homo sapiens ALK tyrosine kinase receptor Proteins 0.000 description 19
• 239000002585 base Substances 0.000 description 19
• 239000002244 precipitate Substances 0.000 description 19
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 18
• 239000007795 chemical reaction product Substances 0.000 description 18
• 150000007529 inorganic bases Chemical class 0.000 description 16
• 229910000027 potassium carbonate Inorganic materials 0.000 description 16
• 150000001335 aliphatic alkanes Chemical class 0.000 description 15
• 235000011181 potassium carbonates Nutrition 0.000 description 15
• 238000003756 stirring Methods 0.000 description 15
• 150000007530 organic bases Chemical class 0.000 description 14
• LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 14
• JVVRJMXHNUAPHW-UHFFFAOYSA-N 1h-pyrazol-5-amine Chemical compound NC=1C=CNN=1 JVVRJMXHNUAPHW-UHFFFAOYSA-N 0.000 description 13
• LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 13
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 13
• 238000005755 formation reaction Methods 0.000 description 13
• 238000010898 silica gel chromatography Methods 0.000 description 13
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 12
• 229910052799 carbon Inorganic materials 0.000 description 12
• 229910000029 sodium carbonate Inorganic materials 0.000 description 12
• 239000005711 Benzoic acid Substances 0.000 description 11
• LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 11
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 11
• 230000009471 action Effects 0.000 description 11
• 229910052786 argon Inorganic materials 0.000 description 11
• 229960004365 benzoic acid Drugs 0.000 description 11
• 239000003795 chemical substances by application Substances 0.000 description 11
• 239000000460 chlorine Substances 0.000 description 11
• 239000013078 crystal Substances 0.000 description 11
• 230000006870 function Effects 0.000 description 11
• 229960002715 nicotine Drugs 0.000 description 11
• 238000003786 synthesis reaction Methods 0.000 description 11
• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 10
• 235000010233 benzoic acid Nutrition 0.000 description 10
• 239000003054 catalyst Substances 0.000 description 10
• 230000003197 catalytic effect Effects 0.000 description 10
• 239000013067 intermediate product Substances 0.000 description 10
• 238000000746 purification Methods 0.000 description 10
• LYDRKKWPKKEMNZ-UHFFFAOYSA-N tert-butyl benzoate Chemical compound CC(C)(C)OC(=O)C1=CC=CC=C1 LYDRKKWPKKEMNZ-UHFFFAOYSA-N 0.000 description 10
• CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 9
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
• 102000001253 Protein Kinase Human genes 0.000 description 9
• 239000002253 acid Substances 0.000 description 9
• 239000008346 aqueous phase Substances 0.000 description 9
• 238000009835 boiling Methods 0.000 description 9
• 210000004027 cell Anatomy 0.000 description 9
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 9
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 9
• 108060006633 protein kinase Proteins 0.000 description 9
• 229920006395 saturated elastomer Polymers 0.000 description 9
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 8
• NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 8
• 239000000706 filtrate Substances 0.000 description 8
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
• 230000002829 reductive effect Effects 0.000 description 8
• YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 0.000 description 8
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 8
• AMFYRKOUWBAGHV-UHFFFAOYSA-N 1h-pyrazolo[4,3-b]pyridine Chemical compound C1=CN=C2C=NNC2=C1 AMFYRKOUWBAGHV-UHFFFAOYSA-N 0.000 description 7
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 7
• BYEUNDASYOFKIW-UHFFFAOYSA-N 5-iodo-2h-pyrazolo[3,4-b]pyridin-3-amine Chemical class C1=C(I)C=C2C(N)=NNC2=N1 BYEUNDASYOFKIW-UHFFFAOYSA-N 0.000 description 7
• XVIHGTRTKQZJAC-UHFFFAOYSA-N 6-chloro-3-nitropyridine-2-carbonitrile Chemical group [O-][N+](=O)C1=CC=C(Cl)N=C1C#N XVIHGTRTKQZJAC-UHFFFAOYSA-N 0.000 description 7
• FHJURFWVUOSFQI-UHFFFAOYSA-N 6-iodopyridin-3-amine Chemical compound NC1=CC=C(I)N=C1 FHJURFWVUOSFQI-UHFFFAOYSA-N 0.000 description 7
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 7
• 239000012425 OXONE® Substances 0.000 description 7
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 7
• 238000004587 chromatography analysis Methods 0.000 description 7
• 239000012043 crude product Substances 0.000 description 7
• 238000010438 heat treatment Methods 0.000 description 7
• 230000005764 inhibitory process Effects 0.000 description 7
• 239000000543 intermediate Substances 0.000 description 7
• 229910052740 iodine Inorganic materials 0.000 description 7
• 239000011630 iodine Substances 0.000 description 7
• 229910052763 palladium Inorganic materials 0.000 description 7
• HJKYXKSLRZKNSI-UHFFFAOYSA-I pentapotassium;hydrogen sulfate;oxido sulfate;sulfuric acid Chemical compound [K+].[K+].[K+].[K+].[K+].OS([O-])(=O)=O.[O-]S([O-])(=O)=O.OS(=O)(=O)O[O-].OS(=O)(=O)O[O-] HJKYXKSLRZKNSI-UHFFFAOYSA-I 0.000 description 7
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 7
• 125000006239 protecting group Chemical group 0.000 description 7
• 239000012312 sodium hydride Substances 0.000 description 7
• 229910000104 sodium hydride Inorganic materials 0.000 description 7
• 235000010288 sodium nitrite Nutrition 0.000 description 7
• 229910052938 sodium sulfate Inorganic materials 0.000 description 7
• 235000011152 sodium sulphate Nutrition 0.000 description 7
• 238000006467 substitution reaction Methods 0.000 description 7
• 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 6
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 6
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 6
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
• 239000007864 aqueous solution Substances 0.000 description 6
• HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 6
• USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 6
• 239000003480 eluent Substances 0.000 description 6
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 6
• 208000027866 inflammatory disease Diseases 0.000 description 6
• 230000002757 inflammatory effect Effects 0.000 description 6
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 6
• SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 6
• 235000001968 nicotinic acid Nutrition 0.000 description 6
• 239000011664 nicotinic acid Substances 0.000 description 6
• 229960003512 nicotinic acid Drugs 0.000 description 6
• 239000000843 powder Substances 0.000 description 6
• 238000006722 reduction reaction Methods 0.000 description 6
• 201000006845 reticulosarcoma Diseases 0.000 description 6
• 208000029922 reticulum cell sarcoma Diseases 0.000 description 6
• 235000017557 sodium bicarbonate Nutrition 0.000 description 6
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
• 238000012360 testing method Methods 0.000 description 6
• RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 6
• FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Chemical compound O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 6
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 5
• MOUURCSKHKVYPB-UHFFFAOYSA-N 2-methylsulfanyl-6-oxo-1h-pyridine-3-carbonitrile Chemical compound CSC1=NC(O)=CC=C1C#N MOUURCSKHKVYPB-UHFFFAOYSA-N 0.000 description 5
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 5
• 229910021595 Copper(I) iodide Inorganic materials 0.000 description 5
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• 230000007017 scission Effects 0.000 description 1
• 239000001632 sodium acetate Substances 0.000 description 1
• 235000017281 sodium acetate Nutrition 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• AVPCPPOOQICIRJ-UHFFFAOYSA-L sodium glycerol 2-phosphate Chemical compound [Na+].[Na+].OCC(CO)OP([O-])([O-])=O AVPCPPOOQICIRJ-UHFFFAOYSA-L 0.000 description 1
• 229940079827 sodium hydrogen sulfite Drugs 0.000 description 1
• 235000009518 sodium iodide Nutrition 0.000 description 1
• 229960001922 sodium perborate Drugs 0.000 description 1
• 229940045872 sodium percarbonate Drugs 0.000 description 1
• GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 1
• CRWJEUDFKNYSBX-UHFFFAOYSA-N sodium;hypobromite Chemical compound [Na+].Br[O-] CRWJEUDFKNYSBX-UHFFFAOYSA-N 0.000 description 1
• YKLJGMBLPUQQOI-UHFFFAOYSA-M sodium;oxidooxy(oxo)borane Chemical compound [Na+].[O-]OB=O YKLJGMBLPUQQOI-UHFFFAOYSA-M 0.000 description 1
• 229910001220 stainless steel Inorganic materials 0.000 description 1
• 239000010935 stainless steel Substances 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 125000003107 substituted aryl group Chemical group 0.000 description 1
• 125000000565 sulfonamide group Chemical group 0.000 description 1
• 150000003456 sulfonamides Chemical class 0.000 description 1
• 150000003871 sulfonates Chemical class 0.000 description 1
• 125000004434 sulfur atom Chemical group 0.000 description 1
• 230000004083 survival effect Effects 0.000 description 1
• 239000000725 suspension Substances 0.000 description 1
• 238000001308 synthesis method Methods 0.000 description 1
• 230000002194 synthesizing effect Effects 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 229960001367 tartaric acid Drugs 0.000 description 1
• 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 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 1
• DFSGLWKPJNAHSD-UHFFFAOYSA-N tert-butyl 2-amino-4-(1-methylpiperidin-4-yl)benzoate Chemical compound C1CN(C)CCC1C1=CC=C(C(=O)OC(C)(C)C)C(N)=C1 DFSGLWKPJNAHSD-UHFFFAOYSA-N 0.000 description 1
• SFRGSLPTHNBRCL-UHFFFAOYSA-N tert-butyl 4-fluoro-2-[2-fluoroethyl(2,2,2-trifluoroethyl)amino]benzoate Chemical compound C(C)(C)(C)OC(C1=C(C=C(C=C1)F)N(CCF)CC(F)(F)F)=O SFRGSLPTHNBRCL-UHFFFAOYSA-N 0.000 description 1
• RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical group CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 description 1
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 1
• QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 150000003568 thioethers Chemical class 0.000 description 1
• 229930192474 thiophene Natural products 0.000 description 1
• 125000003944 tolyl group Chemical group 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
• ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical compound CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 0.000 description 1
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
• 210000004881 tumor cell Anatomy 0.000 description 1
• 230000005748 tumor development Effects 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 229910052727 yttrium Inorganic materials 0.000 description 1
• VWQVUPCCIRVNHF-UHFFFAOYSA-N yttrium atom Chemical compound [Y] VWQVUPCCIRVNHF-UHFFFAOYSA-N 0.000 description 1
• 150000003752 zinc compounds Chemical class 0.000 description 1