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    • 2. 发明申请
    • ASYMMETRIC BENZOXANTHENE DYES
    • 不对称苯并噻嗪染料
    • WO1997036960A1
    • 1997-10-09
    • PCT/US1997005376
    • 1997-04-01
    • THE PERKIN-ELMER CORPORATION
    • THE PERKIN-ELMER CORPORATIONBENSON, Scott, C.MENCHEN, Steven, M.THEISEN, Peter, D.HENNESSEY, Kevin, M.FURNISS, Vergine, C.HAUSER, Joan
    • C09B11/24
    • C07H21/00C07C39/38C09B11/00C09B11/08C12Q1/6869
    • A class of asymmetric monobenzoxanthene compounds useful as fluorescent dyes are disclosed having structure (I) wherein Y1 and Y2 are individually hydroxyl, amino, imminium, or oxygen, R1-R8 are hydrogen, fluorine, chlorine, alkyl, alkene, alkyne, sulfonate, amino, amido, nitrile, alkoxy, linking group, and combinations thereof, and R9 is acetylene, alkane, alkene, cyano, substituted phenyl, and combinations thereof. The invention further includes novel intermediate compounds useful for the synthesis of asymmetric benzoxanthene compounds having general structure (II) where substituents R3-R7 correspond to like-referenced substituents in the structure of described above, and Y2 is hydroxyl or amine. In another aspect, the invention includes methods for synthesizing the above dye compounds and intermediates. In yet another aspect, the present invention includes reagents labeled with the asymmetric benzoxanthene dye compounds, including deoxynucleotides, dideoxynucleotides, phosphoramidites, and polynucleotides. In an additional aspect, the invention includes methods utilizing such dye compounds and reagents including dideoxy polynucleotide sequencing and fragment analysis methods.
    • 公开了一类用作荧光染料的不对称单苯并氧蒽化合物,其结构(I)其中Y 1和Y 2分别是羟基,氨基,亚氨基或氧,R 1 -R 8是氢,氟,氯,烷基,烯烃,炔烃, 氨基,酰氨基,腈,烷氧基,连接基团及其组合,R 9为乙炔,烷烃,烯烃,氰基,取代的苯基及其组合。 本发明还包括可用于合成具有通式结构(II)的不对称苯并氧杂蒽化合物的新型中间体化合物,其中取代基R3-R7对应于上述结构中相似的取代基,而Y2是羟基或胺。 另一方面,本发明包括合成上述染料化合物和中间体的方法。 在另一方面,本发明包括用不对称苯并氧杂蒽染料化合物标记的试剂,包括脱氧核苷酸,双脱氧核苷酸,亚磷酰胺和多核苷酸。 在另一方面,本发明包括利用这种染料化合物的方法和包括双脱氧多核苷酸测序和片段分析方法的试剂。
    • 4. 发明公开
    • SUBSTITUTED PROPARGYLETHOXYAMIDO NUCLEOSIDES
    • 取代的丙酰基乙酰氨基核苷
    • EP0923597A1
    • 1999-06-23
    • EP98914275.0
    • 1998-03-23
    • THE PERKIN-ELMER CORPORATION
    • KHAN, Shaheer, H.MENCHEN, Steven, M.ROSENBLUM, Barnett, B.
    • C12N15C07H19C07H21C12Q1
    • C07H21/00C07H19/04C12Q1/6869Y02P20/55
    • Substituted propargylethoxyamido nucleosides are disclosed having structure (I) wherein X is selected from the group consisting of amino alkanoic acid, alkylamino benzoic acid, α-amino acid, and 4-amino-2-butynoic acid. R1 and R2 taken separately are selected from the group consisting of -H, lower alkyl, protecting group, and label; R3 is selected from the group consisting of -H and lower alkyl. B is a 7-deazapurine, purine, or pyrimidine nucleoside base. When B is purine or 7-deazapurine, the sugar moiety is attached at the N9-position of the purine or deazapurine, and when B is pyrimidine, the sugar moiety is attached at the N1-position of the pyrimidine. When B is a purine, the adjacent triple-bonded carbon is attached to the 8-position of the purine, when B is 7-deazapurine, the adjacent triple-bonded carbon is attached to the 7-position of the 7-deazapurine, and when B is pyrimidine, the adjacent triple-bonded carbon is attached to the 5-position of the pyrimidine. W¿1? is selected from the group consisting of -H and -OH. W2 is -OH or a moiety which renders the nucleoside incapable of forming a phosphodiester bond at the 3'-position. W3 is selected from the group consisting of -PO4, -P2O7, -P3O10, phosphate analog, and -OH. Additionally, a primer extension method is provided employing the above X-substituted propargylethoxyamido nucleosides, and polynucleotides including the above X-substituted propargylethoxyamido nucleosides is provided.
    • 公开了具有结构(I)的取代的炔丙基乙氧基酰胺核苷,其中X选自氨基链烷酸,烷基氨基苯甲酸,α-氨基酸和4-氨基-2-丁炔酸。 R1和R2分别选自-H,低级烷基,保护基和标记; R3选自-H和低级烷基。 B是7-脱氮嘌呤,嘌呤或嘧啶核苷碱基。 当B是嘌呤或7-脱氮嘌呤时,糖部分连接在嘌呤或脱氮嘌呤的N9-位置,并且当B是嘧啶时,糖部分连接在嘧啶的N1位。 当B是嘌呤时,相邻的三键碳连接到嘌呤的8-位,当B是7-脱氮嘌呤时,相邻的三键碳连接到7-脱氮嘌呤的7-位,并且 当B是嘧啶时,相邻的三键碳连接到嘧啶的5-位。 W¿1? 选自-H和-OH。 W2是-OH或使得核苷不能在3'-位形成磷酸二酯键的部分。 W3选自-PO4,-P2O7,-P3O10,磷酸盐类似物和-OH。 此外,提供了使用上述X取代的炔丙基乙氧基酰胺基核苷的引物延伸方法,并且提供了包含上述X取代的炔丙基乙氧基酰胺核苷的多核苷酸。