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1. 发明申请

US20110237786A1 METHOD FOR PREPARING OLIGONUCLEOTIDE 有权
标题翻译：制备寡核苷酸的方法
公开(公告)号：US20110237786A1
公开(公告)日：2011-09-29
申请号：US13003195
申请日：2009-09-22
申请人： Zhen Xi , Jinyu Huang , Junbin Zhang
发明人： Zhen Xi , Jinyu Huang , Junbin Zhang
IPC分类号： C07H23/00 , C07H21/02 , C07H21/04
CPC分类号： C07H21/00 , C07H19/067 , C07H19/10 , C07H19/167 , C07H19/20 , Y02P20/55
摘要： A method for preparing oligonucleotide comprising reacting the compound of Formula (1) with the compound of Formula (2) in a liquid reaction medium under the condition of condensation reaction to obtain the compound of formula (3). In the method according to the present invention, the functional groups are protected by suitable protective groups to only expose the 5′-OH of the compound of Formula (1) (OH-component) and the 3′-phosphate of the compound of Formula (2) (P-component) which are to be connected, so that the condensation reaction is carried out in a liquid reaction medium to bond the OH-component and P-component to obtain DNA or RNA short chain. The method of the present invention does not need a solid phase column and can be carried out in a liquid reaction medium. Thus, oligonucleotides can be synthesized on a large scale.
摘要翻译：一种制备寡核苷酸的方法，包括在缩合反应条件下在液体反应介质中使式（1）化合物与式（2）化合物反应，得到式（3）化合物。在根据本发明的方法中，官能团被合适的保护基保护，仅暴露式（1）化合物（OH-成分）的5'-羟基化合物和式（2）（P-组分），使得缩合反应在液体反应介质中进行以键合OH-组分和P-组分以获得DNA或RNA短链。本发明的方法不需要固相柱，可以在液体反应介质中进行。因此，寡核苷酸可以大规模合成。

2. 发明授权

US09567364B2 Nucleotide and/or oligonucleotide and preparation process thereof 有权
标题翻译：核苷酸和/或寡核苷酸及其制备方法
公开(公告)号：US09567364B2
公开(公告)日：2017-02-14
申请号：US13811295
申请日：2011-07-20
申请人： Zhen Xi , Zicai Liang , Jinyu Huang
发明人： Zhen Xi , Zicai Liang , Jinyu Huang
IPC分类号： C07H21/02 , C07H21/04 , C07H21/00 , C07H19/04 , C07H19/20 , C07H19/10 , C07H19/048 , C07H19/167
CPC分类号： C07H21/02 , C07H19/10 , C07H19/167 , C07H19/20 , C07H21/04 , Y02P20/55
摘要： Nucleotide and/or oligonucleotide represented by formula (1) and the liquid phase synthesis process thereof. The present invention provides a liquid phase synthesis process for preparing a nucleotide and/or an oligonucleotide, comprising a process for combining the nucleotide and/or oligonucleotide protective groups, in which, under the condition that the 2′-hydroxyl group is protected by a group with a sterically hindered silane structure, the 3′ phosphate group(s) of the nucleotide and/or oligonucleotide is/are directly protected by (a)β-cyanoethyl group(s), and after the β-cyanoethyl group(s) is/are removed, the resulting product can directly participate in the next cycle of synthesis, wherein the synthesis reaction is carried out in a reaction flask or reaction kettle, without being limited by a solid carrier or synthesizer, so that the large scale preparation of oligonucleotides can be achieved.
摘要翻译：由式（1）表示的核苷酸和/或寡核苷酸及其液相合成方法。本发明提供了制备核苷酸和/或寡核苷酸的液相合成方法，包括将核苷酸和/或寡核苷酸保护基组合的方法，其中在2'-羟基被具有空间位阻硅烷结构的基团，核苷酸和/或寡核苷酸的3'磷酸基团被（a）2-氰基乙基直接保护，并且在2-氰基乙基之后，所得产物可以直接参与下一个合成循环，其中合成反应在反应烧瓶或反应釜中进行，而不受固体载体或合成仪的限制，从而大规模制备可以实现寡核苷酸。

3. 发明授权

US08569476B2 Method for preparing oligonucleotide 有权
标题翻译：寡核苷酸的制备方法
公开(公告)号：US08569476B2
公开(公告)日：2013-10-29
申请号：US13003195
申请日：2009-09-22
申请人： Zhen Xi , Jinyu Huang , Junbin Zhang
发明人： Zhen Xi , Jinyu Huang , Junbin Zhang
IPC分类号： C07H21/02 , C07H21/00
CPC分类号： C07H21/00 , C07H19/067 , C07H19/10 , C07H19/167 , C07H19/20 , Y02P20/55
摘要： A method for preparing oligonucleotide comprising reacting the compound of Formula (1) with the compound of Formula (2) in a liquid reaction medium under the condition of condensation reaction to obtain the compound of formula (3) is provided. 1-(2-mesitylenesulfonyl)-3-nitro-1H-1,2,4-triazole (MSNT) is applied as condensing agent. Oligonucleotides synthesized in the liquid reaction medium could be obtained on a large scale.
摘要翻译：提供制备寡核苷酸的方法，其包括在缩合反应条件下在液体反应介质中使式（1）化合物与式（2）化合物反应，得到式（3）化合物。应用1-（2-甲磺酰基）-3-硝基-1H-1,2,4-三唑（MSNT）作为缩合剂。在液体反应介质中合成的寡核苷酸可以大规模获得。

4. 发明申请

US20130123482A1 NUCLEOTIDE AND/OR OLIGONUCLEOTIDE AND PREPARATION PROCESS THEREOF 有权
标题翻译：核苷酸和/或寡核苷酸及其制备方法
公开(公告)号：US20130123482A1
公开(公告)日：2013-05-16
申请号：US13811295
申请日：2011-07-20
申请人： Zhen Xi , Zicai Liang , Jinyu Huang
发明人： Zhen Xi , Zicai Liang , Jinyu Huang
IPC分类号： C07H21/02 , C07H21/04
CPC分类号： C07H21/02 , C07H19/10 , C07H19/167 , C07H19/20 , C07H21/04 , Y02P20/55
摘要： Nucleotide and/or oligonucleotide represented by formula (1) and the liquid phase synthesis process thereof. The present invention provides a liquid phase synthesis process for preparing a nucleotide and/or an oligonucleotide, comprising a process for combining the nucleotide and/or oligonucleotide protective groups, in which, under the condition that the 2′-hydroxyl group is protected by a group with a sterically hindered silane structure, the 3′ phosphate group(s) of the nucleotide and/or oligonucleotide is/are directly protected by (a)β-cyanoethyl group(s), and after the β-cyanoethyl group(s) is/are removed, the resulting product can directly participate in the next cycle of synthesis, wherein the synthesis reaction is carried out in a reaction flask or reaction kettle, without being limited by a solid carrier or synthesizer, so that the large scale preparation of oligonucleotides can be achieved.
摘要翻译：由式（1）表示的核苷酸和/或寡核苷酸及其液相合成方法。本发明提供了制备核苷酸和/或寡核苷酸的液相合成方法，包括将核苷酸和/或寡核苷酸保护基组合的方法，其中在2'-羟基被具有空间位阻硅烷结构的基团，核苷酸和/或寡核苷酸的3'磷酸基团被（a）β-氰基乙基直接保护，并且在β-氰基乙基之后，所得产物可以直接参与下一个合成循环，其中合成反应在反应烧瓶或反应釜中进行，而不受固体载体或合成仪的限制，从而大规模制备可以实现寡核苷酸。

5. 发明申请

US20100317714A1 COMPLEX MOLECULE INTERFERING THE EXPRESSION OF TARGET GENES AND ITS PREPARING METHODS 审中-公开
标题翻译：复合分子干扰目标基因的表达及其制备方法
公开(公告)号：US20100317714A1
公开(公告)日：2010-12-16
申请号：US12745322
申请日：2008-11-28
申请人： Zhen Xi , Zicai Liang , Liqiang Cao , Junbin Zhang , Jinyu Huang
发明人： Zhen Xi , Zicai Liang , Liqiang Cao , Junbin Zhang , Jinyu Huang
IPC分类号： A61K31/7088 , C07H21/02 , C07K2/00 , A61P7/00
CPC分类号： C12N15/111 , C12N2310/14 , C12N2310/318 , C12N2310/532
摘要： The present invention provides a complex molecule interfering the expression of target genes and the methods for preparing the complex molecule, wherein the complex molecule contains two siRNA strands X1 and X2 having at least 80% complementarity, the 5′ end of X1 and 3′ end of X2 are linked through non-nucleic acid molecule L1, the 5′ end of X2 and 3′ end of X1 are linked through non-nucleic acid molecule L2. Since both 5′ and 3′ ends of two siRNA strands X1 and X2 of the complex molecule according to the present invention are linked through non-nucleic acid molecules, it is not easy to unwind and degraded for the siRNA strands, and therefore the chemical stability of siRNA and the remaining time in the blood are greatly improved. After being administered, the Dicer enzyme in the cells is utilized to release the locked siRNAs from the complex molecules, and after unwinding, the antisense strand of the siRNA is released from the double-stranded siRNA to inhibit the expression of the target genes.
摘要翻译：本发明提供了干扰靶基因表达的复合分子和制备复合分子的方法，其中复合分子含有两个具有至少80％互补性的siRNA链X1和X2，X1和3'末端的5'末端的X2通过非核酸分子L1连接，X2的5'端和X1的3'末端通过非核酸分子L2连接。由于根据本发明的复合分子的两个siRNA链X1和X2的5'和3'末端都通过非核酸分子连接，所以对于siRNA链来说不容易退化和降解，因此化学 siRNA的稳定性和血液中的剩余时间大大提高。在施用后，细胞中的Dicer酶用于从复合分子中释放锁定的siRNA，并且在解开后，从双链siRNA释放siRNA的反义链以抑制靶基因的表达。

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