公开(公告)号：US08492390B2

公开(公告)日：2013-07-23

申请号：US13336303

申请日：2011-12-23

申请人： Mads Detlef Sorensen ,  Jesper Wengel ,  Troels Koch ,  Signe M. Christensen ,  Christoph Rosenbohm ,  Daniel Sejer Pedersen

发明人： Mads Detlef Sorensen ,  Jesper Wengel ,  Troels Koch ,  Signe M. Christensen ,  Christoph Rosenbohm ,  Daniel Sejer Pedersen

IPC分类号： C07D473/06 ,  C07D473/16 ,  C07D473/18 ,  C07D473/34 ,  C07D473/40 ,  C07D239/70 ,  C07D239/52 ,  A61P31/22

CPC分类号： C07H19/20 ,  C07H19/00 ,  C07H19/04 ,  C07H19/048

摘要： The invention relates to a novel strategy for the synthesis of Locked Nucleic Acid derivatives, such as α-L-oxy-LNA, amino-LNA, α-L-amino-LNA, thio-LNA, α-L-thio-LNA, seleno-LNA and methylene LNA, which provides scalable high yielding reactions utilising intermediates that also can produce other LNA analogues such as oxy-LNA. Also, the compounds of the formula X are important intermediates that may be reacted with varieties of nucleophiles leading to a wide variety of LNA analogues.

摘要翻译： 本发明涉及一种用于合成锁定核酸衍生物的新策略，例如α-L-氧-LNA，氨基-LNA，α-L-氨基-LNA，硫代-LNA，α-L-硫代-LNA， 硒代-LNA和亚甲基LNA，其利用也可以产生其他LNA类似物如oxy-LNA的中间体提供可伸缩的高产反应。 此外，式X的化合物是可能与各种亲核试剂反应的重要中间体，导致各种各样的LNA类似物。

公开(公告)号：US20100216983A1

公开(公告)日：2010-08-26

申请号：US12534711

申请日：2009-08-03

申请人： Mads Detlef Sorensen ,  Jesper Wengel ,  Troels Koch ,  Signe M. Christensen ,  Christoph Rosenbohm ,  Daniel Sejer Pedersen

发明人： Mads Detlef Sorensen ,  Jesper Wengel ,  Troels Koch ,  Signe M. Christensen ,  Christoph Rosenbohm ,  Daniel Sejer Pedersen

IPC分类号： C07H21/00

CPC分类号： C07H19/20 ,  C07H19/00 ,  C07H19/04 ,  C07H19/048

摘要： The invention relates to a novel strategy for the synthesis of Locked Nucleic Acid derivatives, such as α-L-oxy-LNA, amino-LNA, α-L-amino-LNA, thio-LNA, α-L-thio-LNA, seleno-LNA and methylene LNA, which provides scalable high yielding reactions utilising intermediates that also can produce other LNA analogues such as oxy-LNA. Also, the compounds of the formula X are important intermediates that may be reacted with varieties of nucleophiles leading to a wide variety of LNA analogues.

摘要翻译： 本发明涉及一种合成锁定核酸衍生物的新策略，如α-L-氧-LNA，氨基-LNA，α-L-氨基-LNA，硫代-LNA，α-L-硫代-LNA， 硒代-LNA和亚甲基LNA，其利用也可以产生其他LNA类似物如oxy-LNA的中间体提供可伸缩的高产反应。 此外，式X的化合物是可能与各种亲核试剂反应的重要中间体，导致各种各样的LNA类似物。

公开(公告)号：US07569575B2

公开(公告)日：2009-08-04

申请号：US10435607

申请日：2003-05-08

申请人： Mads Detlef Sørensen ,  Jesper Wengel ,  Troels Koch ,  Signe M. Christensen ,  Christoph Rosenbohm ,  Daniel Sejer Pedersen

发明人： Mads Detlef Sørensen ,  Jesper Wengel ,  Troels Koch ,  Signe M. Christensen ,  Christoph Rosenbohm ,  Daniel Sejer Pedersen

IPC分类号： C07D473/06 ,  C07D473/16 ,  C07D473/18 ,  C07D473/34 ,  C07D473/32 ,  C07D473/40 ,  C07D239/10 ,  C07D239/22 ,  A61K31/52 ,  A61K31/522 ,  A61K31/506 ,  A61P31/22

CPC分类号： C07H19/20 ,  C07H19/00 ,  C07H19/04 ,  C07H19/048

摘要： The invention relates to a novel strategy for the synthesis of Locked Nucleic Acid derivatives, such as α-L-oxy-LNA, amino-LNA, α-L-amino-LNA, thio-LNA, α-L-thio-LNA, seleno-LNA and methylene LNA, which provides scalable high yielding reactions utilizing intermediates that also can produce other LNA analogues such as oxy-LNA. Also, the compounds of the formula X are important intermediates that may be reacted with varieties of nucleophiles leading to a wide variety of LNA analogues.

摘要翻译： 本发明涉及一种用于合成锁定核酸衍生物的新策略，例如α-小鼠，L

公开(公告)号：US20120165514A1

公开(公告)日：2012-06-28

申请号：US13336303

申请日：2011-12-23

申请人： Mads Detlef Sørensen ,  Jesper Wengel ,  Troels Koch ,  Signe M. Christensen ,  Christoph Rosenbohm ,  Daniel Sejer Pedersen

发明人： Mads Detlef Sørensen ,  Jesper Wengel ,  Troels Koch ,  Signe M. Christensen ,  Christoph Rosenbohm ,  Daniel Sejer Pedersen

IPC分类号： C07H19/02

CPC分类号： C07H19/20 ,  C07H19/00 ,  C07H19/04 ,  C07H19/048

摘要： The invention relates to a novel strategy for the synthesis of Locked Nucleic Acid derivatives, such as α-L-oxy-LNA, amino-LNA, α-L-amino-LNA, thio-LNA, α-L-thio-LNA, seleno-LNA and methylene LNA, which provides scalable high yielding reactions utilising intermediates that also can produce other LNA analogues such as oxy-LNA. Also, the compounds of the formula X are important intermediates that may be reacted with varieties of nucleophiles leading to a wide variety of LNA analogues.

摘要翻译： 本发明涉及一种合成锁定核酸衍生物的新策略，如α-L-氧-LNA，氨基-LNA，α-L-氨基-LNA，硫代-LNA，α-L-硫代-LNA， 硒代-LNA和亚甲基LNA，其利用也可以产生其他LNA类似物如oxy-LNA的中间体提供可伸缩的高产反应。 此外，式X的化合物是可能与各种亲核试剂反应的重要中间体，导致各种各样的LNA类似物。

公开(公告)号：US08084458B2

公开(公告)日：2011-12-27

申请号：US12534711

申请日：2009-08-03

申请人： Mads Detlef Sørensen ,  Jesper Wengel ,  Troels Koch ,  Signe M. Christensen ,  Christoph Rosenbohm ,  Daniel Sejer Pedersen

发明人： Mads Detlef Sørensen ,  Jesper Wengel ,  Troels Koch ,  Signe M. Christensen ,  Christoph Rosenbohm ,  Daniel Sejer Pedersen

IPC分类号： C07D473/06 ,  C07D473/16 ,  C07D473/18 ,  C07D473/34 ,  C07D473/40 ,  C07D239/10 ,  C07D239/52 ,  A61P31/22

CPC分类号： C07H19/20 ,  C07H19/00 ,  C07H19/04 ,  C07H19/048

摘要： Methods are described for the synthesis of Locked Nucleic Acid (LNA) derivatives using certain nitrogen-containing nucleophiles.

摘要翻译： 描述了使用某些含氮亲核试剂合成锁定核酸（LNA）衍生物的方法。

公开(公告)号：US20100279895A1

公开(公告)日：2010-11-04

申请号：US12192581

申请日：2008-08-15

申请人： Jesper Wengel ,  Poul Nielsen

发明人： Jesper Wengel ,  Poul Nielsen

IPC分类号： C40B40/06 ,  C07H21/00

CPC分类号： C07H21/04

摘要： The present invention relates to novel bicyclic and tricyclic nucleoside and nucleotide analogues as well as to oligonucleotides comprising such elements. The nucleotide analogues, LNAs (Locked Nucleoside Analogues), are able to provide valuable improvements to oligonucleotides with respect to affinity and specificity towards complementary RNA and DNA oligomers. The novel type of LNA modified oligonucleotides, as well as the LNAs as such, are useful in a wide range of diagnostic applications as well as therapeutic applications. Among these can be mentioned antisense applications, PCR applications, strand displacement oligomers, as substrates for nucleic acid polymerases, as nucleotide based drugs, etc. The present invention also relates to such applications.

公开(公告)号：US20090182136A1

公开(公告)日：2009-07-16

申请号：US12294126

申请日：2007-03-23

申请人： Jesper Wengel ,  Jorgen Kjems

发明人： Jesper Wengel ,  Jorgen Kjems

IPC分类号： C12N15/11

CPC分类号： C12N15/111 ,  C12N2310/14 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/3231 ,  C12N2310/3341 ,  C12N2310/3515 ,  C12N2310/53 ,  C12N2320/50 ,  C12N2310/3521

摘要： The present invention is directed to pharmaceutical and therapeutic compositions which comprise RNA complexes comprising an antisense strand and a discontinued passenger strand capable of regulating gene expression. The use of a discontinued passenger strand reduces off target effects of the RNA complexes and also has other advantages.

摘要翻译： 本发明涉及包含含有能够调节基因表达的反义链和中断的乘客链的RNA复合物的药物和治疗组合物。 停用的乘客链的使用降低了RNA复合物的目标效应，并且还具有其它优点。

公开(公告)号：US07053207B2

公开(公告)日：2006-05-30

申请号：US09565699

申请日：2000-05-04

申请人： Jesper Wengel

发明人： Jesper Wengel

IPC分类号： C07H21/02 ,  C07H21/04 ,  C12Q1/68

CPC分类号： C07H9/04 ,  C07H19/06 ,  C07H21/00

摘要： Provided are L-ribo bicyclic nucleotide compounds as well as syntheses of such compounds. The nucleoside compounds of the invention are useful in forming oligonucleotides that can produce nucleobase specific duplexes with complementary single stranded and double stranded nucleic acids.

摘要翻译： 提供L-双环双环核苷酸化合物以及这些化合物的合成。 本发明的核苷化合物可用于形成可与互补单链和双链核酸产生核碱基特异性双链体的寡核苷酸。

公开(公告)号：US20050287566A1

公开(公告)日：2005-12-29

申请号：US11132650

申请日：2005-05-18

申请人： Jesper Wengel ,  Poul Nielsen

发明人： Jesper Wengel ,  Poul Nielsen

IPC分类号： C07H21/04 ,  C12Q1/68

CPC分类号： C07H21/04

摘要： The present invention relates to novel bicyclic and tricyclic nucleoside and nucleotide analogues as well as to oligonucleotides comprising such elements. The nucleotide analogues, LNAs (Locked Nucleoside Analogues), are able to provide valuable improvements to oligonucleotides with respect to affinity and specificity towards complementary RNA and DNA oligomers. The novel type of LNA modified oligonucleotides, as well as the LNAs as such, are useful in a wide range of diagnostic applications as well as therapeutic applications. Among these can be mentioned antisense applications, PCR applications, strand displacement oligomers, as substrates for nucleic acid polymerases, as nucleotide based drugs, etc. The present invention also relates to such applications.

摘要翻译： 本发明涉及新型的双环和三环核苷和核苷酸类似物以及包含这些元件的寡核苷酸。 核苷酸类似物LNA（锁定核苷类似物）能够在对互补RNA和DNA寡聚体的亲和力和特异性方面为寡核苷酸提供有价值的改进。 新型LNA修饰的寡核苷酸以及LNA本身可用于广泛的诊断应用以及治疗应用。 其中可以提及反义应用，PCR应用，链置换寡聚体，作为核酸聚合酶的底物，作为核苷酸的药物等。本发明还涉及这样的应用。

公开(公告)号：US06794499B2

公开(公告)日：2004-09-21

申请号：US09152059

申请日：1998-09-11

申请人： Jesper Wengel ,  Poul Nielsen

发明人： Jesper Wengel ,  Poul Nielsen

IPC分类号： C07H2100

CPC分类号： C07H21/00

摘要： Novel oligomers, and synthesis thereof, comprising one or more bi-, tri, or polycyclic nucleoside analogues are disclosed herein. The nucleoside analogues have a “locked” structure, termed Locked Nucleoside Analogues (LNA). LNA's exhibit highly desirable and useful properties. LNA's are capable of forming nucleobase specific duplexes and triplexes will single and double stranded nucleic acids. These complexes exhibit higher thermostability than the corresponding complexes formed with normal nucleic acids. The properties of LNA's allow for a wide range of uses such as diagnostic agents and therapeutic agents in a mammal suffering from or susceptible to, various diseases.

摘要翻译： 本文公开了包含一种或多种双，三或多环核苷类似物的新型低聚物及其合成。 核苷类似物具有称为锁定核苷类似物（LNA）的“锁定”结构。 LNA的展示非常理想和有用的性能。 LNA能够形成核碱基特异性双链体，并且三链体将单链和双链核酸。 这些配合物表现出比与正常核酸形成的相应复合物更高的热稳定性。 LNA的性质允许在各种疾病患有或易患各种疾病的哺乳动物中广泛使用诸如诊断剂和治疗剂。