CA2771988C - Process for the synthesis of 4,5,6,7-tetrachloro-3',6'-dihydroxy-2',4',5',7'-tetraiodo-3h-spiro[isobenzofuran-1,9'-xanthen]-3-one (rose bengal) and related xanthenes - Google Patents
Process for the synthesis of 4,5,6,7-tetrachloro-3',6'-dihydroxy-2',4',5',7'-tetraiodo-3h-spiro[isobenzofuran-1,9'-xanthen]-3-one (rose bengal) and related xanthenes Download PDFInfo
- Publication number
- CA2771988C CA2771988C CA2771988A CA2771988A CA2771988C CA 2771988 C CA2771988 C CA 2771988C CA 2771988 A CA2771988 A CA 2771988A CA 2771988 A CA2771988 A CA 2771988A CA 2771988 C CA2771988 C CA 2771988C
- Authority
- CA
- Canada
- Prior art keywords
- formula
- compound
- iodine
- solution
- acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000000034 method Methods 0.000 title claims abstract description 131
- 230000008569 process Effects 0.000 title claims abstract description 93
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 20
- 150000003732 xanthenes Chemical class 0.000 title abstract description 15
- IICCLYANAQEHCI-UHFFFAOYSA-N 4,5,6,7-tetrachloro-3',6'-dihydroxy-2',4',5',7'-tetraiodospiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C(C(=C(Cl)C(Cl)=C2Cl)Cl)=C2C21C1=CC(I)=C(O)C(I)=C1OC1=C(I)C(O)=C(I)C=C21 IICCLYANAQEHCI-UHFFFAOYSA-N 0.000 title description 22
- 238000003786 synthesis reaction Methods 0.000 title description 10
- 229930187593 rose bengal Natural products 0.000 title 1
- 229940081623 rose bengal Drugs 0.000 title 1
- STRXNPAVPKGJQR-UHFFFAOYSA-N rose bengal A Natural products O1C(=O)C(C(=CC=C2Cl)Cl)=C2C21C1=CC(I)=C(O)C(I)=C1OC1=C(I)C(O)=C(I)C=C21 STRXNPAVPKGJQR-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 150
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims abstract description 58
- 239000012535 impurity Substances 0.000 claims abstract description 53
- 239000002904 solvent Substances 0.000 claims abstract description 24
- -1 hypochlorite ions Chemical class 0.000 claims abstract description 20
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 14
- WQYVRQLZKVEZGA-UHFFFAOYSA-N hypochlorite Inorganic materials Cl[O-] WQYVRQLZKVEZGA-UHFFFAOYSA-N 0.000 claims abstract description 10
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000007800 oxidant agent Substances 0.000 claims abstract description 9
- 238000004519 manufacturing process Methods 0.000 claims abstract description 8
- 238000011065 in-situ storage Methods 0.000 claims abstract description 7
- 229910052740 iodine Inorganic materials 0.000 claims description 67
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 57
- 239000011630 iodine Substances 0.000 claims description 56
- 239000000203 mixture Substances 0.000 claims description 53
- 239000000243 solution Substances 0.000 claims description 51
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 44
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 38
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 36
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 32
- 238000002360 preparation method Methods 0.000 claims description 32
- 229910052801 chlorine Inorganic materials 0.000 claims description 31
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 22
- 239000002516 radical scavenger Substances 0.000 claims description 20
- 229910052794 bromium Inorganic materials 0.000 claims description 19
- 239000003929 acidic solution Substances 0.000 claims description 18
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 16
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 16
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 16
- 239000011734 sodium Substances 0.000 claims description 16
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 15
- 238000010438 heat treatment Methods 0.000 claims description 15
- 239000000725 suspension Substances 0.000 claims description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 14
- 229910052708 sodium Inorganic materials 0.000 claims description 14
- 235000009518 sodium iodide Nutrition 0.000 claims description 14
- 239000007864 aqueous solution Substances 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 11
- 235000010265 sodium sulphite Nutrition 0.000 claims description 11
- HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Chemical compound [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 claims description 10
- 229910052700 potassium Inorganic materials 0.000 claims description 10
- XZIYJVFHFHYPHS-UHFFFAOYSA-N 4,4',5,5',6,7-hexachloro-3',6'-dihydroxy-2',7'-diiodospiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C(C(=C(Cl)C(Cl)=C2Cl)Cl)=C2C21C1=CC(I)=C(O)C(Cl)=C1OC1=C(Cl)C(O)=C(I)C=C21 XZIYJVFHFHYPHS-UHFFFAOYSA-N 0.000 claims description 9
- 239000002585 base Substances 0.000 claims description 9
- NLTATQHSRPCJAH-UHFFFAOYSA-N 2',4,5,6,7,7'-hexachloro-3',6'-dihydroxy-4',5'-diiodospiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C(C(=C(Cl)C(Cl)=C2Cl)Cl)=C2C21C1=CC(Cl)=C(O)C(I)=C1OC1=C(I)C(O)=C(Cl)C=C21 NLTATQHSRPCJAH-UHFFFAOYSA-N 0.000 claims description 8
- HFKCVAAQEVKLRR-UHFFFAOYSA-N 4,4',5,6,7-pentachloro-3',6'-dihydroxy-2',5',7'-triiodospiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C(C(=C(Cl)C(Cl)=C2Cl)Cl)=C2C21C1=CC(I)=C(O)C(I)=C1OC1=C(Cl)C(O)=C(I)C=C21 HFKCVAAQEVKLRR-UHFFFAOYSA-N 0.000 claims description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 8
- 229910052744 lithium Inorganic materials 0.000 claims description 8
- 238000002844 melting Methods 0.000 claims description 7
- 230000008018 melting Effects 0.000 claims description 7
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 6
- MLMLMXDCMFGFMG-UHFFFAOYSA-N 2',4,5,6,7-pentachloro-3',6'-dihydroxy-4',5',7'-triiodospiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C(C(=C(Cl)C(Cl)=C2Cl)Cl)=C2C21C1=CC(I)=C(O)C(I)=C1OC1=C(I)C(O)=C(Cl)C=C21 MLMLMXDCMFGFMG-UHFFFAOYSA-N 0.000 claims description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 5
- XYXNTHIYBIDHGM-UHFFFAOYSA-N ammonium thiosulfate Chemical compound [NH4+].[NH4+].[O-]S([O-])(=O)=S XYXNTHIYBIDHGM-UHFFFAOYSA-N 0.000 claims description 5
- FGRVOLIFQGXPCT-UHFFFAOYSA-L dipotassium;dioxido-oxo-sulfanylidene-$l^{6}-sulfane Chemical compound [K+].[K+].[O-]S([O-])(=O)=S FGRVOLIFQGXPCT-UHFFFAOYSA-L 0.000 claims description 5
- 229920000642 polymer Polymers 0.000 claims description 5
- 239000011736 potassium bicarbonate Substances 0.000 claims description 5
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 5
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 5
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 5
- BHZRJJOHZFYXTO-UHFFFAOYSA-L potassium sulfite Chemical compound [K+].[K+].[O-]S([O-])=O BHZRJJOHZFYXTO-UHFFFAOYSA-L 0.000 claims description 5
- 235000019252 potassium sulphite Nutrition 0.000 claims description 5
- 150000003254 radicals Chemical class 0.000 claims description 5
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical group [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 claims description 5
- 235000019345 sodium thiosulphate Nutrition 0.000 claims description 5
- 238000003828 vacuum filtration Methods 0.000 claims description 5
- PHLREGDKKFAHDX-UHFFFAOYSA-N 2',4,5,5',6,7-hexachloro-3',6'-dihydroxy-4',7'-diiodospiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C(C(=C(Cl)C(Cl)=C2Cl)Cl)=C2C21C1=CC(Cl)=C(O)C(I)=C1OC1=C(Cl)C(O)=C(I)C=C21 PHLREGDKKFAHDX-UHFFFAOYSA-N 0.000 claims description 4
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 claims description 3
- 239000002841 Lewis acid Substances 0.000 claims description 3
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 3
- 229940092714 benzenesulfonic acid Drugs 0.000 claims description 3
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 claims description 3
- 230000006872 improvement Effects 0.000 claims description 3
- 235000019260 propionic acid Nutrition 0.000 claims description 3
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 3
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims 12
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims 4
- 239000003637 basic solution Substances 0.000 claims 4
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 claims 4
- 238000001816 cooling Methods 0.000 claims 1
- 239000012065 filter cake Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 17
- 238000007363 ring formation reaction Methods 0.000 abstract description 12
- 238000006192 iodination reaction Methods 0.000 abstract description 11
- 230000026045 iodination Effects 0.000 abstract description 10
- 238000001914 filtration Methods 0.000 abstract description 7
- 239000003960 organic solvent Substances 0.000 abstract description 3
- 238000000605 extraction Methods 0.000 abstract description 2
- 230000007717 exclusion Effects 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 60
- 239000000460 chlorine Substances 0.000 description 35
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 28
- 239000011541 reaction mixture Substances 0.000 description 24
- 239000007787 solid Substances 0.000 description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- GHMLBKRAJCXXBS-UHFFFAOYSA-N resorcinol Chemical compound OC1=CC=CC(O)=C1 GHMLBKRAJCXXBS-UHFFFAOYSA-N 0.000 description 18
- 238000004128 high performance liquid chromatography Methods 0.000 description 15
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 13
- 239000000543 intermediate Substances 0.000 description 13
- 239000000047 product Substances 0.000 description 12
- 229910052731 fluorine Inorganic materials 0.000 description 11
- 238000002955 isolation Methods 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 229910052736 halogen Inorganic materials 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 8
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
- 150000002367 halogens Chemical class 0.000 description 8
- 150000002596 lactones Chemical group 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 238000000746 purification Methods 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- AUHHYELHRWCWEZ-UHFFFAOYSA-N tetrachlorophthalic anhydride Chemical compound ClC1=C(Cl)C(Cl)=C2C(=O)OC(=O)C2=C1Cl AUHHYELHRWCWEZ-UHFFFAOYSA-N 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 210000000056 organ Anatomy 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 description 5
- 230000000875 corresponding effect Effects 0.000 description 5
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical class O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 238000007086 side reaction Methods 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- 238000004808 supercritical fluid chromatography Methods 0.000 description 5
- OALHHIHQOFIMEF-UHFFFAOYSA-N 3',6'-dihydroxy-2',4',5',7'-tetraiodo-3h-spiro[2-benzofuran-1,9'-xanthene]-3-one Chemical class O1C(=O)C2=CC=CC=C2C21C1=CC(I)=C(O)C(I)=C1OC1=C(I)C(O)=C(I)C=C21 OALHHIHQOFIMEF-UHFFFAOYSA-N 0.000 description 4
- AFQUMYICNSZTNS-UHFFFAOYSA-N 4,5,6,7-tetrabromo-3',6'-dihydroxy-2',4',5',7'-tetraiodospiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C(C(=C(Br)C(Br)=C2Br)Br)=C2C21C1=CC(I)=C(O)C(I)=C1OC1=C(I)C(O)=C(I)C=C21 AFQUMYICNSZTNS-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 239000003086 colorant Substances 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 230000008030 elimination Effects 0.000 description 4
- 238000003379 elimination reaction Methods 0.000 description 4
- IINNWAYUJNWZRM-UHFFFAOYSA-L erythrosin B Chemical class [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(I)C(=O)C(I)=C2OC2=C(I)C([O-])=C(I)C=C21 IINNWAYUJNWZRM-UHFFFAOYSA-L 0.000 description 4
- 238000010791 quenching Methods 0.000 description 4
- 239000002002 slurry Substances 0.000 description 4
- 235000011121 sodium hydroxide Nutrition 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- SWZVJOLLQTWFCW-UHFFFAOYSA-N 2-chlorobenzene-1,3-diol Chemical compound OC1=CC=CC(O)=C1Cl SWZVJOLLQTWFCW-UHFFFAOYSA-N 0.000 description 3
- QCPFFGGFHNZBEP-UHFFFAOYSA-N 4,5,6,7-tetrachloro-3',6'-dihydroxyspiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C(C(=C(Cl)C(Cl)=C2Cl)Cl)=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 QCPFFGGFHNZBEP-UHFFFAOYSA-N 0.000 description 3
- JQVAPEJNIZULEK-UHFFFAOYSA-N 4-chlorobenzene-1,3-diol Chemical compound OC1=CC=C(Cl)C(O)=C1 JQVAPEJNIZULEK-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 239000005708 Sodium hypochlorite Substances 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 239000008139 complexing agent Substances 0.000 description 3
- 239000002537 cosmetic Substances 0.000 description 3
- 239000006184 cosolvent Substances 0.000 description 3
- 229940011411 erythrosine Drugs 0.000 description 3
- 239000004174 erythrosine Substances 0.000 description 3
- 235000012732 erythrosine Nutrition 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- QDLAGTHXVHQKRE-UHFFFAOYSA-N lichenxanthone Natural products COC1=CC(O)=C2C(=O)C3=C(C)C=C(OC)C=C3OC2=C1 QDLAGTHXVHQKRE-UHFFFAOYSA-N 0.000 description 3
- 239000000651 prodrug Substances 0.000 description 3
- 229940002612 prodrug Drugs 0.000 description 3
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 150000005207 1,3-dihydroxybenzenes Chemical class 0.000 description 2
- DCHBAXDAGSOKLD-UHFFFAOYSA-N 2',4,5,6,7,7'-hexachloro-3',6'-dihydroxyspiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C(C(=C(Cl)C(Cl)=C2Cl)Cl)=C2C21C1=CC(Cl)=C(O)C=C1OC1=C2C=C(Cl)C(O)=C1 DCHBAXDAGSOKLD-UHFFFAOYSA-N 0.000 description 2
- QJUTTWXBKJSCFI-UHFFFAOYSA-N 2',4,5,6,7-pentachloro-3',6'-dihydroxyspiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C(C(=C(Cl)C(Cl)=C2Cl)Cl)=C2C21C1=CC(Cl)=C(O)C=C1OC1=CC(O)=CC=C21 QJUTTWXBKJSCFI-UHFFFAOYSA-N 0.000 description 2
- PBSCGXANFMHYDW-UHFFFAOYSA-N 4,4',5,5',6,7-hexachloro-3',6'-dihydroxyspiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C(C(=C(Cl)C(Cl)=C2Cl)Cl)=C2C21C1=CC=C(O)C(Cl)=C1OC1=C(Cl)C(O)=CC=C21 PBSCGXANFMHYDW-UHFFFAOYSA-N 0.000 description 2
- NOFLFOUIYVIMPV-UHFFFAOYSA-N 4,4',5,6,7-pentachloro-3',6'-dihydroxyspiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C(C(=C(Cl)C(Cl)=C2Cl)Cl)=C2C21C1=CC=C(O)C(Cl)=C1OC1=CC(O)=CC=C21 NOFLFOUIYVIMPV-UHFFFAOYSA-N 0.000 description 2
- QEQZYXUCEUYYLX-UHFFFAOYSA-N 4,5,6,7-tetrabromo-2',7'-dichloro-3',6'-dihydroxy-4',5'-diiodospiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C(C(=C(Br)C(Br)=C2Br)Br)=C2C21C1=CC(Cl)=C(O)C(I)=C1OC1=C(I)C(O)=C(Cl)C=C21 QEQZYXUCEUYYLX-UHFFFAOYSA-N 0.000 description 2
- IPHIVMNSLCJINU-UHFFFAOYSA-N 4,5,6,7-tetrabromo-2'-chloro-3',6'-dihydroxy-4',5',7'-triiodospiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C(C(=C(Br)C(Br)=C2Br)Br)=C2C21C1=CC(I)=C(O)C(I)=C1OC1=C(I)C(O)=C(Cl)C=C21 IPHIVMNSLCJINU-UHFFFAOYSA-N 0.000 description 2
- ONFYALQBOJKJFC-UHFFFAOYSA-N 4,5,6,7-tetrabromo-3',6'-dihydroxy-2',4',5'-triiodospiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C(C(=C(Br)C(Br)=C2Br)Br)=C2C21C1=CC(I)=C(O)C(I)=C1OC1=C(I)C(O)=CC=C21 ONFYALQBOJKJFC-UHFFFAOYSA-N 0.000 description 2
- DDXCXUMXVNCVSV-UHFFFAOYSA-N 4,5,6,7-tetrachloro-3',6'-dihydroxy-2',4',7'-triiodospiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C(C(=C(Cl)C(Cl)=C2Cl)Cl)=C2C21C1=CC(I)=C(O)C(I)=C1OC1=C2C=C(I)C(O)=C1 DDXCXUMXVNCVSV-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000000113 differential scanning calorimetry Methods 0.000 description 2
- UMHPIQAUVJDYJN-UHFFFAOYSA-L disodium 9-(2-carboxy-3,4,5,6-tetrachlorophenyl)-2,4,5,7-tetraiodo-6-oxoxanthen-3-olate Chemical compound [Na+].[Na+].Oc1c(I)cc2c(-c3c(Cl)c(Cl)c(Cl)c(Cl)c3C([O-])=O)c3cc(I)c(=O)c(I)c3oc2c1I.Oc1c(I)cc2c(-c3c(Cl)c(Cl)c(Cl)c(Cl)c3C([O-])=O)c3cc(I)c(=O)c(I)c3oc2c1I UMHPIQAUVJDYJN-UHFFFAOYSA-L 0.000 description 2
- UWBXIFCTIZXXLS-UHFFFAOYSA-L disodium;2,3,4,5-tetrachloro-6-(2,4,5,7-tetraiodo-3-oxido-6-oxoxanthen-9-yl)benzoate Chemical compound [Na+].[Na+].[O-]C(=O)C1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1C1=C2C=C(I)C(=O)C(I)=C2OC2=C(I)C([O-])=C(I)C=C21 UWBXIFCTIZXXLS-UHFFFAOYSA-L 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 229960001483 eosin Drugs 0.000 description 2
- SEACYXSIPDVVMV-UHFFFAOYSA-L eosin Y Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C([O-])=C(Br)C=C21 SEACYXSIPDVVMV-UHFFFAOYSA-L 0.000 description 2
- 239000000989 food dye Substances 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 239000013067 intermediate product Substances 0.000 description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 229910001416 lithium ion Inorganic materials 0.000 description 2
- IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 238000012797 qualification Methods 0.000 description 2
- 230000000171 quenching effect Effects 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 239000013557 residual solvent Substances 0.000 description 2
- 229920002477 rna polymer Polymers 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- VYOVNJLXKINTQB-UHFFFAOYSA-N 1-iodo-9H-xanthene Chemical group IC1=CC=CC=2OC3=CC=CC=C3CC1=2 VYOVNJLXKINTQB-UHFFFAOYSA-N 0.000 description 1
- VFNKZQNIXUFLBC-UHFFFAOYSA-N 2',7'-dichlorofluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(Cl)=C(O)C=C1OC1=C2C=C(Cl)C(O)=C1 VFNKZQNIXUFLBC-UHFFFAOYSA-N 0.000 description 1
- HYYHUFWEVUNHPI-UHFFFAOYSA-N 2,3,4,5-tetrabromo-6-(2,5-dichloro-3-hydroxy-4,7-diiodo-6-oxo-8a,9-dihydroxanthen-9-yl)benzoic acid Chemical compound OC(=O)C1=C(Br)C(Br)=C(Br)C(Br)=C1C1C2=CC(Cl)=C(O)C(I)=C2OC2=C(Cl)C(=O)C(I)=CC21 HYYHUFWEVUNHPI-UHFFFAOYSA-N 0.000 description 1
- AVWQIURZAOWRPT-UHFFFAOYSA-N 2,3,4,5-tetrabromo-6-(2,7-dichloro-3-hydroxy-4,5-diiodo-6-oxo-8a,9-dihydroxanthen-9-yl)benzoic acid Chemical compound OC(=O)C1=C(Br)C(Br)=C(Br)C(Br)=C1C1C2=CC(Cl)=C(O)C(I)=C2OC2=C(I)C(=O)C(Cl)=CC21 AVWQIURZAOWRPT-UHFFFAOYSA-N 0.000 description 1
- SBHKTOKZRKXBCU-UHFFFAOYSA-N 2,3,4,5-tetrabromo-6-(2-chloro-3-hydroxy-4,5,7-triiodo-6-oxo-8a,9-dihydroxanthen-9-yl)benzoic acid Chemical compound OC(=O)C1=C(Br)C(Br)=C(Br)C(Br)=C1C1C2=CC(Cl)=C(O)C(I)=C2OC2=C(I)C(=O)C(I)=CC21 SBHKTOKZRKXBCU-UHFFFAOYSA-N 0.000 description 1
- PTCUBBBOXTXZAR-UHFFFAOYSA-N 2,3,4,5-tetrabromo-6-(3-hydroxy-2,4,5,7-tetraiodo-6-oxoxanthen-9-yl)benzoic acid Chemical compound OC(=O)C1=C(Br)C(Br)=C(Br)C(Br)=C1C1=C2C=C(I)C(=O)C(I)=C2OC2=C(I)C(O)=C(I)C=C21 PTCUBBBOXTXZAR-UHFFFAOYSA-N 0.000 description 1
- BJMLEZMLXDBHAI-UHFFFAOYSA-N 2,3,4,5-tetrabromo-6-(3-hydroxy-2,4,5-triiodo-6-oxoxanthen-9-yl)benzoic acid Chemical compound OC(=O)C1=C(Br)C(Br)=C(Br)C(Br)=C1C(C1=CC(I)=C(O)C(I)=C1O1)=C2C1=C(I)C(=O)C=C2 BJMLEZMLXDBHAI-UHFFFAOYSA-N 0.000 description 1
- GQAZWXHTZHSNTI-UHFFFAOYSA-N 2,3,4,5-tetrabromo-6-(3-hydroxy-2,4,7-triiodo-6-oxoxanthen-9-yl)benzoic acid Chemical compound OC(=O)C1=C(Br)C(Br)=C(Br)C(Br)=C1C(C1=CC(I)=C(O)C(I)=C1O1)=C2C1=CC(=O)C(I)=C2 GQAZWXHTZHSNTI-UHFFFAOYSA-N 0.000 description 1
- ZPRZVKRPNFQBCH-UHFFFAOYSA-N 2,3,4,5-tetrabromo-6-(4,5-dichloro-3-hydroxy-2,7-diiodo-6-oxo-8a,9-dihydroxanthen-9-yl)benzoic acid Chemical compound OC(=O)C1=C(Br)C(Br)=C(Br)C(Br)=C1C1C2=CC(I)=C(O)C(Cl)=C2OC2=C(Cl)C(=O)C(I)=CC21 ZPRZVKRPNFQBCH-UHFFFAOYSA-N 0.000 description 1
- IQKKPPQMGRMDNE-UHFFFAOYSA-N 2,3,4,5-tetrabromo-6-(4,7-dichloro-3-hydroxy-2,5-diiodo-6-oxo-8a,9-dihydroxanthen-9-yl)benzoic acid Chemical compound OC(=O)C1=C(Br)C(Br)=C(Br)C(Br)=C1C1C2=CC(I)=C(O)C(Cl)=C2OC2=C(I)C(=O)C(Cl)=CC21 IQKKPPQMGRMDNE-UHFFFAOYSA-N 0.000 description 1
- DSHMNIPSSBTRMS-UHFFFAOYSA-N 2,3,4,5-tetrabromo-6-(4-chloro-3-hydroxy-2,5,7-triiodo-6-oxo-8a,9-dihydroxanthen-9-yl)benzoic acid Chemical compound OC(=O)C1=C(Br)C(Br)=C(Br)C(Br)=C1C1C2=CC(I)=C(O)C(Cl)=C2OC2=C(I)C(=O)C(I)=CC21 DSHMNIPSSBTRMS-UHFFFAOYSA-N 0.000 description 1
- UWWBNJIJUGWSLN-UHFFFAOYSA-N 2,3,4,5-tetrabromo-6-(5-chloro-3-hydroxy-2,4,7-triiodo-6-oxo-8a,9-dihydroxanthen-9-yl)benzoic acid Chemical compound OC(=O)C1=C(Br)C(Br)=C(Br)C(Br)=C1C1C2=CC(I)=C(O)C(I)=C2OC2=C(Cl)C(=O)C(I)=CC21 UWWBNJIJUGWSLN-UHFFFAOYSA-N 0.000 description 1
- FFQRBSFTLSKOPO-UHFFFAOYSA-N 2,3,4,5-tetrabromo-6-(7-chloro-3-hydroxy-2,4,5-triiodo-6-oxo-8a,9-dihydroxanthen-9-yl)benzoic acid Chemical compound OC(=O)C1=C(Br)C(Br)=C(Br)C(Br)=C1C1C2=CC(I)=C(O)C(I)=C2OC2=C(I)C(=O)C(Cl)=CC21 FFQRBSFTLSKOPO-UHFFFAOYSA-N 0.000 description 1
- NLJUBSUXNFTFON-UHFFFAOYSA-N 2,3,4,5-tetrachloro-6-(2,5-dichloro-3-hydroxy-4,7-diiodo-6-oxoxanthen-9-yl)benzoic acid Chemical compound OC(=O)C1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1C1=C2C=C(I)C(=O)C(Cl)=C2OC2=C(I)C(O)=C(Cl)C=C21 NLJUBSUXNFTFON-UHFFFAOYSA-N 0.000 description 1
- RZSZOCZAJYRTHZ-UHFFFAOYSA-N 2,3,4,5-tetrachloro-6-(2,7-dichloro-3-hydroxy-4,5-diiodo-6-oxoxanthen-9-yl)benzoic acid Chemical compound OC(=O)C1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1C1=C2C=C(Cl)C(=O)C(I)=C2OC2=C(I)C(O)=C(Cl)C=C21 RZSZOCZAJYRTHZ-UHFFFAOYSA-N 0.000 description 1
- OVIIPQKXDJLMLO-UHFFFAOYSA-N 2,3,4,5-tetrachloro-6-(2-chloro-3-hydroxy-4,5,7-triiodo-6-oxoxanthen-9-yl)benzoic acid Chemical compound OC(=O)C1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1C1=C2C=C(I)C(=O)C(I)=C2OC2=C(I)C(O)=C(Cl)C=C21 OVIIPQKXDJLMLO-UHFFFAOYSA-N 0.000 description 1
- CBQCSTHMYMLFSD-UHFFFAOYSA-N 2,3,4,5-tetrachloro-6-(3-hydroxy-2,4,5-triiodo-6-oxoxanthen-9-yl)benzoic acid Chemical compound OC(=O)C1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1C(C1=CC(I)=C(O)C(I)=C1O1)=C2C1=C(I)C(=O)C=C2 CBQCSTHMYMLFSD-UHFFFAOYSA-N 0.000 description 1
- WAKLGVCHSHETDB-UHFFFAOYSA-N 2,3,4,5-tetrachloro-6-(3-hydroxy-2,4,7-triiodo-6-oxoxanthen-9-yl)benzoic acid Chemical compound OC(=O)C1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1C(C1=CC(I)=C(O)C(I)=C1O1)=C2C1=CC(=O)C(I)=C2 WAKLGVCHSHETDB-UHFFFAOYSA-N 0.000 description 1
- AOLZJFWTXWRGBM-UHFFFAOYSA-N 2,3,4,5-tetrachloro-6-(4,5-dichloro-3-hydroxy-2,7-diiodo-6-oxoxanthen-9-yl)benzoic acid Chemical compound OC(=O)C1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1C1=C2C=C(I)C(=O)C(Cl)=C2OC2=C(Cl)C(O)=C(I)C=C21 AOLZJFWTXWRGBM-UHFFFAOYSA-N 0.000 description 1
- VOYQVJYICCNMBZ-UHFFFAOYSA-N 2,3,4,5-tetrachloro-6-(4-chloro-3-hydroxy-2,5,7-triiodo-6-oxoxanthen-9-yl)benzoic acid Chemical compound OC(=O)C1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1C1=C2C=C(I)C(=O)C(I)=C2OC2=C(Cl)C(O)=C(I)C=C21 VOYQVJYICCNMBZ-UHFFFAOYSA-N 0.000 description 1
- BNJXHRMYHDWZKL-UHFFFAOYSA-N 2-iodobenzene-1,3-diol Chemical class OC1=CC=CC(O)=C1I BNJXHRMYHDWZKL-UHFFFAOYSA-N 0.000 description 1
- WUMMJTQRPVPQSK-UHFFFAOYSA-N 4,5,6,7-tetrabromo-3',6'-dihydroxy-2',4',7'-triiodospiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C(C(=C(Br)C(Br)=C2Br)Br)=C2C21C1=CC(I)=C(O)C(I)=C1OC1=C2C=C(I)C(O)=C1 WUMMJTQRPVPQSK-UHFFFAOYSA-N 0.000 description 1
- IPKCUTPQPWOPLA-UHFFFAOYSA-N 4,5,6,7-tetrabromo-4',5'-dichloro-3',6'-dihydroxy-2',7'-diiodospiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C(C(=C(Br)C(Br)=C2Br)Br)=C2C21C1=CC(I)=C(O)C(Cl)=C1OC1=C(Cl)C(O)=C(I)C=C21 IPKCUTPQPWOPLA-UHFFFAOYSA-N 0.000 description 1
- OTVCURBZZGYKKC-UHFFFAOYSA-N 4,5,6,7-tetrabromo-4'-chloro-3',6'-dihydroxy-2',5',7'-triiodospiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C(C(=C(Br)C(Br)=C2Br)Br)=C2C21C1=CC(I)=C(O)C(I)=C1OC1=C(Cl)C(O)=C(I)C=C21 OTVCURBZZGYKKC-UHFFFAOYSA-N 0.000 description 1
- HYANQVFXFBJGDP-UHFFFAOYSA-N 4,5,6,7-tetrachloro-3',6'-dihydroxy-2',4',5'-triiodospiro[2-benzofuran-3,9'-xanthene]-1-one Chemical compound O1C(=O)C(C(=C(Cl)C(Cl)=C2Cl)Cl)=C2C21C1=CC(I)=C(O)C(I)=C1OC1=C(I)C(O)=CC=C21 HYANQVFXFBJGDP-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical group COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- SJISCEAZUHNOMD-UHFFFAOYSA-N 4-phenylcyclohexan-1-amine Chemical compound C1CC(N)CCC1C1=CC=CC=C1 SJISCEAZUHNOMD-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 208000031295 Animal disease Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-OUBTZVSYSA-N Carbon-13 Chemical compound [13C] OKTJSMMVPCPJKN-OUBTZVSYSA-N 0.000 description 1
- 235000014653 Carica parviflora Nutrition 0.000 description 1
- 241000243321 Cnidaria Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- QFVNURBUUYRSTH-UHFFFAOYSA-N OC(=O)C1=C(Br)C(Br)=C(Br)C(Br)=C1C1=C2C=C(I)C(=O)C(I)=C2OC2=C(I)C(O)=CC=C21 Chemical compound OC(=O)C1=C(Br)C(Br)=C(Br)C(Br)=C1C1=C2C=C(I)C(=O)C(I)=C2OC2=C(I)C(O)=CC=C21 QFVNURBUUYRSTH-UHFFFAOYSA-N 0.000 description 1
- LGHGZUMCLLUEEI-UHFFFAOYSA-N OC(=O)C1=C(Br)C(Br)=C(Br)C(Br)=C1C1=C2C=C(I)C(=O)C(I)=C2OC2=CC(O)=C(I)C=C21 Chemical compound OC(=O)C1=C(Br)C(Br)=C(Br)C(Br)=C1C1=C2C=C(I)C(=O)C(I)=C2OC2=CC(O)=C(I)C=C21 LGHGZUMCLLUEEI-UHFFFAOYSA-N 0.000 description 1
- SINRSZYUCAKWPY-UHFFFAOYSA-N OC(=O)C1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1C1=C2C=C(Cl)C(=O)C(I)=C2OC2=C(Cl)C(O)=C(I)C=C21 Chemical compound OC(=O)C1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1C1=C2C=C(Cl)C(=O)C(I)=C2OC2=C(Cl)C(O)=C(I)C=C21 SINRSZYUCAKWPY-UHFFFAOYSA-N 0.000 description 1
- SILZNWXZJNZSJR-UHFFFAOYSA-N OC(=O)C1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1C1=C2C=C(Cl)C(=O)C(I)=C2OC2=C(I)C(O)=C(I)C=C21 Chemical compound OC(=O)C1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1C1=C2C=C(Cl)C(=O)C(I)=C2OC2=C(I)C(O)=C(I)C=C21 SILZNWXZJNZSJR-UHFFFAOYSA-N 0.000 description 1
- OPKXNSSUAWJUJN-UHFFFAOYSA-N OC(=O)C1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1C1=C2C=C(I)C(=O)C(Cl)=C2OC2=C(I)C(O)=C(I)C=C21 Chemical compound OC(=O)C1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1C1=C2C=C(I)C(=O)C(Cl)=C2OC2=C(I)C(O)=C(I)C=C21 OPKXNSSUAWJUJN-UHFFFAOYSA-N 0.000 description 1
- SFBZWDQUMCICCG-UHFFFAOYSA-N OC(=O)C1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1C1=C2C=C(I)C(=O)C(I)=C2OC2=C(I)C(O)=CC=C21 Chemical compound OC(=O)C1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1C1=C2C=C(I)C(=O)C(I)=C2OC2=C(I)C(O)=CC=C21 SFBZWDQUMCICCG-UHFFFAOYSA-N 0.000 description 1
- GOOZVWJTVDSRCD-UHFFFAOYSA-N OC(=O)C1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1C1=C2C=C(I)C(=O)C(I)=C2OC2=CC(O)=C(I)C=C21 Chemical compound OC(=O)C1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1C1=C2C=C(I)C(=O)C(I)=C2OC2=CC(O)=C(I)C=C21 GOOZVWJTVDSRCD-UHFFFAOYSA-N 0.000 description 1
- 208000022873 Ocular disease Diseases 0.000 description 1
- 208000030852 Parasitic disease Diseases 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- QHWKHLYUUZGSCW-UHFFFAOYSA-N Tetrabromophthalic anhydride Chemical compound BrC1=C(Br)C(Br)=C2C(=O)OC(=O)C2=C1Br QHWKHLYUUZGSCW-UHFFFAOYSA-N 0.000 description 1
- 101150046432 Tril gene Proteins 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 238000011210 chromatographic step Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000000973 cosmetic coloring agent Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 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 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000003463 hyperproliferative effect Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 230000002601 intratumoral effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- 239000008017 pharmaceutical colorant Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 238000002428 photodynamic therapy Methods 0.000 description 1
- 150000003022 phthalic acids Chemical class 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 235000011118 potassium hydroxide Nutrition 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 210000005000 reproductive tract Anatomy 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- VDNLFJGJEQUWRB-UHFFFAOYSA-N rose bengal free acid Chemical compound OC(=O)C1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1C1=C2C=C(I)C(=O)C(I)=C2OC2=C(I)C(O)=C(I)C=C21 VDNLFJGJEQUWRB-UHFFFAOYSA-N 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000004753 textile Substances 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 238000003354 tissue distribution assay Methods 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 238000005944 trans-halogenation reaction Methods 0.000 description 1
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
- 235000019798 tripotassium phosphate Nutrition 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/78—Ring systems having three or more relevant rings
- C07D311/80—Dibenzopyrans; Hydrogenated dibenzopyrans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/78—Ring systems having three or more relevant rings
- C07D311/80—Dibenzopyrans; Hydrogenated dibenzopyrans
- C07D311/82—Xanthenes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/10—Spiro-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Virology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pulmonology (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyrane Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Medicinal Preparation (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US24370109P | 2009-09-18 | 2009-09-18 | |
| US61/243,701 | 2009-09-18 | ||
| PCT/US2010/049341 WO2011035161A1 (en) | 2009-09-18 | 2010-09-17 | Process for the synthesis of 4,5,6,7-tetrachloro-3',6'-dihydroxy-2',4',5'7'-tetraiodo-3h-spiro[isobenzofuran-1,9'-xanthen]-3-one (rose bengal) and related xanthenes |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2771988A1 CA2771988A1 (en) | 2011-03-24 |
| CA2771988C true CA2771988C (en) | 2016-07-05 |
Family
ID=43757167
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2771988A Active CA2771988C (en) | 2009-09-18 | 2010-09-17 | Process for the synthesis of 4,5,6,7-tetrachloro-3',6'-dihydroxy-2',4',5',7'-tetraiodo-3h-spiro[isobenzofuran-1,9'-xanthen]-3-one (rose bengal) and related xanthenes |
Country Status (9)
| Country | Link |
|---|---|
| US (2) | US8530675B2 (en:Method) |
| EP (1) | EP2464225B8 (en:Method) |
| JP (1) | JP5671040B2 (en:Method) |
| KR (1) | KR101494055B1 (en:Method) |
| CN (1) | CN102548406B (en:Method) |
| CA (1) | CA2771988C (en:Method) |
| ES (1) | ES2548575T3 (en:Method) |
| MX (1) | MX2012003063A (en:Method) |
| WO (1) | WO2011035161A1 (en:Method) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2828940C (en) | 2011-03-10 | 2024-04-16 | Provectus Pharmaceuticals, Inc. | Combination of local and systemic immunomodulative therapies for enhanced treatment of cancer |
| WO2015059467A1 (en) | 2013-10-22 | 2015-04-30 | SETNA, Rohan | Rose bengal for detection of oxidative decomposition of contaminants |
| JP7015232B2 (ja) * | 2018-11-21 | 2022-02-02 | 東レ・ファインケミカル株式会社 | 高純度のフルオレセイン類化合物の製造方法 |
| JP7617845B2 (ja) * | 2019-02-26 | 2025-01-20 | エフ． ホフマン－ラ ロシュ アーゲー | （６Ｓ）－３－［（４Ｓ）－４－シアノ－２－オキソ－ピロリジン－１－イル］－６－メチル－Ｎ－（３，４，５－トリフルオロフェニル）－６，７－ジヒドロ－４Ｈ－ピラゾロ［１，５－ａ］ピラジン－５－カルボキサミドの調製のための方法 |
| US11938182B2 (en) | 2020-03-26 | 2024-03-26 | Provectus Pharmatech, Inc. | Halogenated xanthenes as vaccine adjuvants |
| AU2021242300B8 (en) * | 2020-03-26 | 2025-08-07 | Provectus Pharmatech, Inc. | Novel uses of halogenated xanthenes in oncology and virology |
| US20240325341A1 (en) * | 2023-03-29 | 2024-10-03 | Provectus Pharmatech, Inc. | Anti-bacterial effect of halogenated fluoresceins against colistin-resistant gram-negative bacteria |
Family Cites Families (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE108838C (en:Method) | ||||
| US1965842A (en) * | 1931-11-21 | 1934-07-10 | Nat Aniline & Chem Co Inc | Production of hydroxybenzenephthaleins |
| US1931049A (en) * | 1931-11-21 | 1933-10-17 | Nat Aniline & Chem Co Inc | Process of making dihydroxyfluoranes |
| US3829440A (en) * | 1972-12-21 | 1974-08-13 | Richardson Merrell Inc | Xanthene derivatives |
| SU517222A1 (ru) | 1974-10-25 | 1977-06-25 | Институт Биофизики Министерства Здравохранения Ссср | Способ получени препарата бенгальска роза, меченного радиоизотопами йода |
| SU792878A1 (ru) | 1978-08-29 | 1982-02-07 | Ленинградский институт ядерной физики им. Б.П.Константинова | Способ получени галогенированных производных флуоресцеина,меченных радиоизотопом йода |
| EP0050684B1 (en) | 1980-10-27 | 1986-01-22 | Syva Company | Novel ether substituted fluorescein compounds as fluorescers and quenchers |
| SU992516A1 (ru) | 1981-06-11 | 1983-01-30 | Ленинградский Институт Ядерной Физики Им.Б.П.Константинова | Способ получени галогенированных производных флуоресцеина,меченных радиоизотопом иода -123 |
| ES8606451A1 (es) | 1985-10-28 | 1986-04-16 | Zoster Sa | Procedimiento para la obtencion de la eritrosina sodica |
| IN168346B (en:Method) | 1987-09-07 | 1991-03-16 | Council Scient Ind Res | |
| US5637733A (en) * | 1995-09-27 | 1997-06-10 | Warner-Jenkinson Company, Inc. | Syntheses of fluorescein compounds with excess resorcinol as a solvent |
| US6252024B1 (en) * | 1995-10-23 | 2001-06-26 | Novartis Ag | Fluorescent N-alkylated acrylamide copolymers and optical pH sensors |
| US6162931A (en) * | 1996-04-12 | 2000-12-19 | Molecular Probes, Inc. | Fluorinated xanthene derivatives |
| US5945526A (en) * | 1996-05-03 | 1999-08-31 | Perkin-Elmer Corporation | Energy transfer dyes with enhanced fluorescence |
| US6331286B1 (en) * | 1998-12-21 | 2001-12-18 | Photogen, Inc. | Methods for high energy phototherapeutics |
| US7648695B2 (en) | 1998-08-06 | 2010-01-19 | Provectus Pharmatech, Inc. | Medicaments for chemotherapeutic treatment of disease |
| US6372907B1 (en) * | 1999-11-03 | 2002-04-16 | Apptera Corporation | Water-soluble rhodamine dye peptide conjugates |
| US6448407B1 (en) * | 2000-11-01 | 2002-09-10 | Pe Corporation (Ny) | Atropisomers of asymmetric xanthene fluorescent dyes and methods of DNA sequencing and fragment analysis |
| AU2002256991A1 (en) * | 2001-02-05 | 2002-08-19 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Healt | Use of 9h-xanthenes in a method of inhibiting viral replication targeting the nucleocapsid protein |
| US6800765B2 (en) * | 2001-08-02 | 2004-10-05 | Molecular Devices Corporation | Fluorescent pH indicators for intracellular assays |
| CA2490961A1 (en) * | 2002-07-01 | 2004-01-08 | Guava Technologies, Inc. | Fluorescent dyes, energy transfer couples and methods |
| FR2846331B1 (fr) * | 2002-10-29 | 2006-11-17 | Synth Innove Lab | Phtaleines de purete elevee et leur procede de preparation |
| WO2004078479A2 (en) * | 2003-02-28 | 2004-09-16 | Polaroid Corporation | Imaging system |
| WO2006001925A1 (en) * | 2004-06-10 | 2006-01-05 | Xantech Pharmaceuticals, Inc. | Diagnostic agents for positron emission imaging using radiolabeled halogenated xanthenes and methods for positron emission imaging with radiolabeled halogenated xanthene diagnostic agents |
| US7736624B2 (en) * | 2006-06-19 | 2010-06-15 | Univ Vanderbilt | Methods and compositions for diagnostic and therapeutic targeting of COX-2 |
| GB0613287D0 (en) | 2006-07-05 | 2006-08-16 | Ge Healthcare Ltd | Dye imaging agents |
| ITMI20061713A1 (it) * | 2006-09-08 | 2008-03-09 | St Microelectronics Srl | Procedimento per la sintesi di derivati alogenati della fluoresceina utili nella produzione di dispositivi di memoria non volatile |
-
2010
- 2010-09-17 CN CN201080041506.7A patent/CN102548406B/zh active Active
- 2010-09-17 EP EP10817918.5A patent/EP2464225B8/en active Active
- 2010-09-17 ES ES10817918.5T patent/ES2548575T3/es active Active
- 2010-09-17 CA CA2771988A patent/CA2771988C/en active Active
- 2010-09-17 KR KR1020127009834A patent/KR101494055B1/ko active Active
- 2010-09-17 MX MX2012003063A patent/MX2012003063A/es unknown
- 2010-09-17 WO PCT/US2010/049341 patent/WO2011035161A1/en not_active Ceased
- 2010-09-17 US US12/884,833 patent/US8530675B2/en active Active
- 2010-09-17 JP JP2012529937A patent/JP5671040B2/ja active Active
-
2013
- 2013-06-12 US US13/916,408 patent/US9422260B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| US9422260B2 (en) | 2016-08-23 |
| US8530675B2 (en) | 2013-09-10 |
| CA2771988A1 (en) | 2011-03-24 |
| KR101494055B1 (ko) | 2015-02-16 |
| JP5671040B2 (ja) | 2015-02-18 |
| CN102548406A (zh) | 2012-07-04 |
| JP2013505261A (ja) | 2013-02-14 |
| EP2464225B1 (en) | 2015-09-16 |
| CN102548406B (zh) | 2015-04-08 |
| EP2464225A4 (en) | 2013-03-27 |
| HK1172501A1 (en) | 2013-04-26 |
| MX2012003063A (es) | 2012-07-25 |
| EP2464225B8 (en) | 2017-08-23 |
| KR20120091088A (ko) | 2012-08-17 |
| HK1172212A1 (zh) | 2013-04-19 |
| US20110071217A1 (en) | 2011-03-24 |
| ES2548575T3 (es) | 2015-10-19 |
| WO2011035161A1 (en) | 2011-03-24 |
| US20130274322A1 (en) | 2013-10-17 |
| EP2464225A1 (en) | 2012-06-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2771988C (en) | Process for the synthesis of 4,5,6,7-tetrachloro-3',6'-dihydroxy-2',4',5',7'-tetraiodo-3h-spiro[isobenzofuran-1,9'-xanthen]-3-one (rose bengal) and related xanthenes | |
| CN111484477B (zh) | 一种苯并吡啶酮杂环化合物及其用途 | |
| CA2736097C (en) | Carbazole compounds for inhibition of nf-kb activity | |
| SU1181540A3 (ru) | Способ получени сульфамоилзамещенного производного фенэтиламина и его кислотной соли | |
| WO2001064664A1 (en) | Reagents for the quantitation of active oxygen | |
| BR112021006843A2 (pt) | benzoxazol e compostos relacionados úteis como moduladores de autofagia mediada por chaperona | |
| US9273022B2 (en) | Process for the synthesis of 4,5,6,7-tetrachloro-3′,6′-dihydroxy-2′, 4′, 5′7′-tetraiodo-3H-spiro[isobenzofuran-1,9′-xanthen]-3-one (Rose Bengal) and related xanthenes | |
| AU674542B2 (en) | Process for obtaining benzoxazines useful for the synthesis of ofloxacin, levofloxacin and derivatives thereof | |
| US20070167350A1 (en) | Quinaldine based semisquaraines and squaraine dyes, process for preparation thereof and use thereof | |
| CN110143955B (zh) | 含杂环侧链的噁二唑衍生物、合成方法及其应用 | |
| WO2011064237A1 (en) | Crystalline forms of substituted pyrazolopyrimidines | |
| JP2690012B2 (ja) | １，２，４―トリオキサン誘導体 | |
| HK1172501B (en) | Process for the synthesis of 4,5,6,7-tetrachloro-3',6'-dihydroxy-2',4',5',7'-tetraiodo-3h-spiro[isobenzofuran-1,9'-xanthen]-3-one (rose bengal) and related xanthenes | |
| JP2025512815A (ja) | ヒストン脱アセチル化酵素６阻害剤としての１，３，４－オキサジアゾール誘導体化合物およびその用途 | |
| EP0866692A1 (fr) | Utilisation de derives de bicycles mono- ou dicetoniques, composes obtenus et leur application comme medicament destine au traitement des inflammations, de la migraine et des etats de chocs | |
| CN115536571A (zh) | 一种吲哚衍生物的制备方法 | |
| OA13294A (fr) | Molécules duales contenant un dérivé peroxydique, leur synthèse et leurs applications thérapeutiques. | |
| JP7731573B2 (ja) | スルフィニル基又はスルホニル基を含むジアミノベンゼン系化合物若しくはその塩、及びそれらを有する有機蛍光材料 | |
| CH634071A5 (en) | Therapeutically active pyranoquinolones | |
| WO2025045168A1 (zh) | 一种大环化合物及其用途 | |
| CH618977A5 (en:Method) | ||
| RU2645679C1 (ru) | Способ получения 7-замещенных 4,4-диметил-9-оксо-4,4а-дигидро-9Н-ксантен-2-карбоновых кислот и их цитотоксическая активность | |
| CN111349059B (zh) | 一类手性环氧化合物的制备方法 | |
| FR2692578A1 (fr) | Dérivés d'indolizines, procédé de préparation et utilisation pour la préparation de composés aminoalkoxybenzènesulfonyl-indolizines à activité pharmaceutique. | |
| KR102046605B1 (ko) | 가시광선-감응성 황화 수소 전달용 조성물 및 이의 용도 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20130625 |