JP2001506686A - ハロレピジンから誘導できるヘリウム−ネオン励起性網状赤血球染色用色素 - Google Patents
ハロレピジンから誘導できるヘリウム−ネオン励起性網状赤血球染色用色素Info
- Publication number
- JP2001506686A JP2001506686A JP52669798A JP52669798A JP2001506686A JP 2001506686 A JP2001506686 A JP 2001506686A JP 52669798 A JP52669798 A JP 52669798A JP 52669798 A JP52669798 A JP 52669798A JP 2001506686 A JP2001506686 A JP 2001506686A
- Authority
- JP
- Japan
- Prior art keywords
- group
- rings
- compound
- dye
- alkyl
- 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.)
- Granted
Links
- 210000001995 reticulocyte Anatomy 0.000 title abstract description 42
- CPBQJMYROZQQJC-UHFFFAOYSA-N helium neon Chemical compound [He].[Ne] CPBQJMYROZQQJC-UHFFFAOYSA-N 0.000 title abstract description 11
- 238000010186 staining Methods 0.000 title description 14
- 238000000034 method Methods 0.000 claims abstract description 32
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 17
- 125000005647 linker group Chemical group 0.000 claims abstract description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 31
- 125000003118 aryl group Chemical group 0.000 claims description 31
- 125000004432 carbon atom Chemical group C* 0.000 claims description 22
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 15
- 150000001875 compounds Chemical class 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 229910052736 halogen Inorganic materials 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 239000011669 selenium Substances 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 125000005842 heteroatom Chemical group 0.000 claims description 9
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 8
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- 239000001301 oxygen Substances 0.000 claims description 7
- 229910052711 selenium Inorganic materials 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 150000002391 heterocyclic compounds Chemical class 0.000 claims description 6
- 239000011593 sulfur Substances 0.000 claims description 6
- 239000007795 chemical reaction product Substances 0.000 claims description 5
- 238000010992 reflux Methods 0.000 claims description 5
- 239000003054 catalyst Substances 0.000 claims description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 4
- 150000002500 ions Chemical class 0.000 claims description 4
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 3
- 239000005977 Ethylene Substances 0.000 claims description 3
- 238000000684 flow cytometry Methods 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 238000010191 image analysis Methods 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- ZQUVDXMUKIVNOW-UHFFFAOYSA-N n,n'-diphenylmethanimidamide Chemical compound C=1C=CC=CC=1NC=NC1=CC=CC=C1 ZQUVDXMUKIVNOW-UHFFFAOYSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 3
- 125000003282 alkyl amino group Chemical group 0.000 claims 2
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 230000009089 cytolysis Effects 0.000 claims 1
- 239000000975 dye Substances 0.000 abstract description 103
- 210000004369 blood Anatomy 0.000 abstract description 14
- 239000008280 blood Substances 0.000 abstract description 13
- 238000001514 detection method Methods 0.000 abstract description 7
- 230000021615 conjugation Effects 0.000 abstract description 3
- 230000002194 synthesizing effect Effects 0.000 abstract description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 239000000523 sample Substances 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 13
- 238000002360 preparation method Methods 0.000 description 13
- 230000027455 binding Effects 0.000 description 11
- 210000003743 erythrocyte Anatomy 0.000 description 10
- 108020004414 DNA Proteins 0.000 description 9
- 238000010521 absorption reaction Methods 0.000 description 9
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 239000012491 analyte Substances 0.000 description 8
- 125000001424 substituent group Chemical group 0.000 description 8
- DPKHZNPWBDQZCN-UHFFFAOYSA-N acridine orange free base Chemical compound C1=CC(N(C)C)=CC2=NC3=CC(N(C)C)=CC=C3C=C21 DPKHZNPWBDQZCN-UHFFFAOYSA-N 0.000 description 7
- DZBUGLKDJFMEHC-UHFFFAOYSA-N benzoquinolinylidene Natural products C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 7
- 239000012876 carrier material Substances 0.000 description 7
- 230000005284 excitation Effects 0.000 description 7
- SQHOAFZGYFNDQX-UHFFFAOYSA-N ethyl-[7-(ethylamino)-2,8-dimethylphenothiazin-3-ylidene]azanium;chloride Chemical compound [Cl-].S1C2=CC(=[NH+]CC)C(C)=CC2=NC2=C1C=C(NCC)C(C)=C2 SQHOAFZGYFNDQX-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 238000003018 immunoassay Methods 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- -1 7-chlorolepidine 3-chloroaniline Chemical compound 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- ZFFFXKCZHWHRET-UHFFFAOYSA-N tert-butyl n-(2-bromo-6-chloropyridin-3-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=C(Cl)N=C1Br ZFFFXKCZHWHRET-UHFFFAOYSA-N 0.000 description 3
- PNPCRKVUWYDDST-UHFFFAOYSA-N 3-chloroaniline Chemical compound NC1=CC=CC(Cl)=C1 PNPCRKVUWYDDST-UHFFFAOYSA-N 0.000 description 2
- OUFGWFRCXZIEPM-UHFFFAOYSA-N 7-chloro-4-methylquinoline Chemical compound ClC1=CC=C2C(C)=CC=NC2=C1 OUFGWFRCXZIEPM-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 150000003973 alkyl amines Chemical group 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 150000007523 nucleic acids Chemical group 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- INCIMLINXXICKS-UHFFFAOYSA-M pyronin Y Chemical compound [Cl-].C1=CC(=[N+](C)C)C=C2OC3=CC(N(C)C)=CC=C3C=C21 INCIMLINXXICKS-UHFFFAOYSA-M 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- DIQSNTFKLAYVOT-UHFFFAOYSA-N 1,3,3-trimethoxybutane Chemical compound COCCC(C)(OC)OC DIQSNTFKLAYVOT-UHFFFAOYSA-N 0.000 description 1
- QBQDROYKEQDPRX-UHFFFAOYSA-N 2,3-dimethyl-1,3-benzothiazol-3-ium Chemical compound C1=CC=C2[N+](C)=C(C)SC2=C1 QBQDROYKEQDPRX-UHFFFAOYSA-N 0.000 description 1
- DHYHYLGCQVVLOQ-UHFFFAOYSA-N 3-bromoaniline Chemical compound NC1=CC=CC(Br)=C1 DHYHYLGCQVVLOQ-UHFFFAOYSA-N 0.000 description 1
- OGRZMXBJGTZUGN-UHFFFAOYSA-N 3-ethyl-2-methyl-1,3-benzothiazol-3-ium Chemical class C1=CC=C2[N+](CC)=C(C)SC2=C1 OGRZMXBJGTZUGN-UHFFFAOYSA-N 0.000 description 1
- QZVQQUVWFIZUBQ-UHFFFAOYSA-N 3-fluoroaniline Chemical group NC1=CC=CC(F)=C1 QZVQQUVWFIZUBQ-UHFFFAOYSA-N 0.000 description 1
- AGMXSOARXXPPIJ-UHFFFAOYSA-N 7-bromo-4-methylquinoline Chemical compound BrC1=CC=C2C(C)=CC=NC2=C1 AGMXSOARXXPPIJ-UHFFFAOYSA-N 0.000 description 1
- ITOHSZXAKKBTMJ-UHFFFAOYSA-N 7-fluoro-4-methylquinoline Chemical compound FC1=CC=C2C(C)=CC=NC2=C1 ITOHSZXAKKBTMJ-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 241000254060 Aquatica lateralis Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 241000207961 Sesamum Species 0.000 description 1
- 235000003434 Sesamum indicum Nutrition 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000003432 anti-folate effect Effects 0.000 description 1
- 229940127074 antifolate Drugs 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 125000000853 cresyl group Chemical group C1(=CC=C(C=C1)C)* 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000010437 erythropoiesis Effects 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
- 229940044631 ferric chloride hexahydrate Drugs 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000004052 folic acid antagonist Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 208000007475 hemolytic anemia Diseases 0.000 description 1
- 238000007074 heterocyclization reaction Methods 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- NQXWGWZJXJUMQB-UHFFFAOYSA-K iron trichloride hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].Cl[Fe+]Cl NQXWGWZJXJUMQB-UHFFFAOYSA-K 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- CXKWCBBOMKCUKX-UHFFFAOYSA-M methylene blue Chemical compound [Cl-].C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 CXKWCBBOMKCUKX-UHFFFAOYSA-M 0.000 description 1
- 229960000907 methylthioninium chloride Drugs 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 238000007431 microscopic evaluation Methods 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000007837 multiplex assay Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000006862 quantum yield reaction Methods 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229920002477 rna polymer Polymers 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 239000012192 staining solution Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 239000011715 vitamin B12 Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/30—Staining; Impregnating ; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B23/00—Methine or polymethine dyes, e.g. cyanine dyes
- C09B23/02—Methine or polymethine dyes, e.g. cyanine dyes the polymethine chain containing an odd number of >CH- or >C[alkyl]- groups
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S436/00—Chemistry: analytical and immunological testing
- Y10S436/80—Fluorescent dyes, e.g. rhodamine
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/11—Automated chemical analysis
- Y10T436/117497—Automated chemical analysis with a continuously flowing sample or carrier stream
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Physics & Mathematics (AREA)
- Biomedical Technology (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Non-Silver Salt Photosensitive Materials And Non-Silver Salt Photography (AREA)
- Holo Graphy (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1. (a)第1複素環部分、(b)第2複素環部分、及び(c)第1及び第2 複素環部分を結合する連結基を有する色素であって、前記第1及び第2複素環部 分は少なくとも2個の環を含有していなければならず、前記複素環部分は第1部 分が第2部分にエチレンにより結合しているコンジュゲートであることを特徴と する色素。 2. 連結基に結び付いている第1部分の環が5員環又は6員環であってよい、 請求項1の化合物。 3. 連結基に結び付いている第2部分の環が5員環又は6員環であってよい、 請求項1の化合物。 4. 下記の構造を有する化合物: 式中、 R1、R2、R3、R4は独立して水素、ハロゲン、シアノ、アルキル、アリール 、アルカリール、アラルキルからなる群から選択された基を表す、又はR1及び R2は一緒になって、又はR2及びR3は一緒になって、又はR3及びR4は一緒に なって、1個以上の環を表す; R5はアルキル基又はアリール基を表す; R6、R7、R8、R9は独立して水素、ハロゲン、シアノ、アルキル、アリール 、アルカリール、アラルキルからなる群から選択された基を表す、又は少なくと もR6、R7、R8、R9の少なくとも1つがハロゲンを表すことを条件に、R6及 びR7は一緒になって、又はR7及びR8は一緒になって、又はR8及びR9は一緒 になって、1個以上の環を表す; R10は、アルキル基又はアリール基を表す; R11、R12は独立して水素、ハロゲン、シアノ、アルキル、アリール、アルカ リール、アラルキルからなる群から選択された基を表す、又はR11及びR12は一 緒になって、1個以上の環を表す; R13は水素又はアルキル基を表す; Yは、YがNではないことを条件に、S、O、C、又はSe を表す; nは0〜3の数字を表す;及び X-は対イオンを表す。 5. R5が1〜20個の炭素原子を有するアルキル基を表す、請求項4の化合 物。 6. R10が1〜20個の炭素原子を有するアルキル基を表す請求項4の化合物 。 7. R5が、好ましくは5個以下の環、より好ましくは3個以下の環、最も好 ましくは1個以下の環を有するアリール基を表す、請求項4の化合物。 8. R10が、好ましくは5個以下の環、より好ましくは3個以下の環、最も好 ましくは1個以下の環を有するアリール基を表す、請求項4の化合物。 9. R5が、好ましくは2〜20個の炭素原子、より好ましくは2〜10個の 炭素原子を有するアルケニル基を表す、請求項4の化合物。 10. R10が、好ましくは2〜20個の炭素原子、より好ましくは2〜10個 の炭素原子を有するアルケニル基を表す、請求項4の化合物。 11. R5がヘテロアリール基を表し、ヘテロ原子は窒素、硫黄、酸素、及び セレンからなる群から選択できる、請求項4の化合物。 12. R10がヘテロアリール基を表し、ヘテロ原子は窒素、硫黄、酸素、及び セレンからなる群から選択できる、請求項4の化合物。 13. R6、R7、R8、又はR9の少なくとも1つがF、Cl、及びIからなる 群から選択される、請求項4の化合物。 14. 還流条件下で第三級アルキルアミン触媒の存在下において、N,N‘− ジフェニルホルムアミジン、無水酢酸及び少なくとも2個の縮合環を含有する複 素環式化合物の反応生成物とアルキル化ハロレピジンとを反応させるステップを 含有する、請求項4の化合物を調製する方法。 15. 前記アルキル化ハロレピジンがハロアニリンとトリアルコキシアルカン との反応生成物である、請求項14の方法。 16. 少なくとも2個の縮合環を含有している前記複素環式化合物が、ヨウ化 2−メチル−N−アルキルベンゾチアゾリウム、ヨウ化2−メチル−N−アルキ ルベンゾキサゾリウム、ヨウ化2−メチル−N−アルキルナフトキサゾリウム、 及びヨウ 化2−メチル−N−アルキルナフトチアゾリウムからなる群から選択される、請 求項14の方法。 17. ハロレピジンと、少なくとも2個の縮合環及び活性化メチル基を含有す る複素環式化合物と無水酢酸及びN,N‘−ジフェニルホルムアニジンとの反応 生成物とを、還流条件下で第三級アルキルアミン触媒の存在下において反応させ るステップを含有する、請求項4の化合物を調製するための方法。 18. 前記アルキル化ハロレピジンがハロアニリンとトリアルコキシアルカン との反応生成物である、請求項17の方法。 19. 少なくとも2個の縮合環を含有している前記複素環式化合物がヨウ化2 −メチル−N−アルキルベンゾチアゾリウム、ヨウ化2−メチル−N−アルキル ベンゾキサゾリウム、ヨウ化2−メチル−N−アルキルナフトキサゾリウム、及 びヨウ化2−メチル−N−アルキルナフトチアゾリウムからなる群から選択され ている、請求項17の方法。 20. a. 試料を提供するステップ, b. 前記試料から細胞を単離するステップ, c. 前記試料へ溶解を導入するステップ, d. 請求項1の色素を前記試料へ添加するステップ, e. 前記試料の蛍光を測定するステップ,を含む細胞表現型を免疫タイピン グする方法。 21. 細胞表現型を免疫タイピングする前記方法がフローサイトメトリーであ る、請求項20の方法。 22. 細胞表現型を免疫タイピングする前記方法が画像分析である、請求項2 1の方法。
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US08/763,022 | 1996-12-10 | ||
US08/763,022 US6495692B1 (en) | 1996-12-10 | 1996-12-10 | Helium-neon excitable reticulocyte dyes derivable from halolepidines |
PCT/US1997/021392 WO1998026007A1 (en) | 1996-12-10 | 1997-11-19 | Helium-neon excitable reticulocyte dyes derivable from halolepidines |
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JP2009052977A Division JP2009167191A (ja) | 1996-12-10 | 2009-03-06 | ハロレピジンから誘導できるヘリウム−ネオン励起性網状赤血球染色用色素 |
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JP2001506686A true JP2001506686A (ja) | 2001-05-22 |
JP4454046B2 JP4454046B2 (ja) | 2010-04-21 |
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JP52669798A Expired - Fee Related JP4454046B2 (ja) | 1996-12-10 | 1997-11-19 | ヘリウム−ネオン励起性色素を用いた試験サンプル中の分析物を検出するための方法 |
JP2009052977A Pending JP2009167191A (ja) | 1996-12-10 | 2009-03-06 | ハロレピジンから誘導できるヘリウム−ネオン励起性網状赤血球染色用色素 |
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JP2009052977A Pending JP2009167191A (ja) | 1996-12-10 | 2009-03-06 | ハロレピジンから誘導できるヘリウム−ネオン励起性網状赤血球染色用色素 |
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US (2) | US6495692B1 (ja) |
EP (1) | EP0944672B1 (ja) |
JP (2) | JP4454046B2 (ja) |
AT (1) | ATE223461T1 (ja) |
CA (1) | CA2273959C (ja) |
DE (1) | DE69715242T2 (ja) |
ES (1) | ES2186008T3 (ja) |
WO (1) | WO1998026007A1 (ja) |
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CN101750274B (zh) | 2008-12-17 | 2014-06-25 | 深圳迈瑞生物医疗电子股份有限公司 | 白细胞分类计数试剂、试剂盒以及白细胞分类计数的方法 |
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JP2009545645A (ja) * | 2006-07-31 | 2009-12-24 | ジーイー・ヘルスケア・アクスイェ・セルスカプ | 非対称フルオロ置換ポリメチン色素 |
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ATE223461T1 (de) | 2002-09-15 |
EP0944672B1 (en) | 2002-09-04 |
US20030145394A1 (en) | 2003-08-07 |
JP2009167191A (ja) | 2009-07-30 |
US7083982B2 (en) | 2006-08-01 |
JP4454046B2 (ja) | 2010-04-21 |
CA2273959A1 (en) | 1998-06-18 |
WO1998026007A1 (en) | 1998-06-18 |
US6495692B1 (en) | 2002-12-17 |
DE69715242D1 (de) | 2002-10-10 |
ES2186008T3 (es) | 2003-05-01 |
EP0944672A1 (en) | 1999-09-29 |
CA2273959C (en) | 2007-07-03 |
DE69715242T2 (de) | 2003-08-07 |
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