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1. 发明申请

WO2007062664A2 ENZYMATIC ENCODING METHODS FOR EFFICIENT SYNTHESIS OF LARGE LIBRARIES 审中-公开
标题翻译：用于大型图书馆有效合成的酶编码方法
公开(公告)号：WO2007062664A2
公开(公告)日：2007-06-07
申请号：PCT/DK2006000685
申请日：2006-12-01
申请人： NUEVOLUTION AS , FRANCH THOMAS , LUNDORF MIKKEL DYBRO , JAKOBSEN SOEREN NYBOE , OLSEN EVA KAMPMANN , ANDERSEN ANNE LEE , HOLTMANN ANETTE , HANSEN ANDERS HOLM , SOERENSEN ANDERS MALLING , GOLDBECH ANNE , DE LEON DAEN , KALDOR DITTE KIVSMOSE , SLOEK FRANK ABILGAARD , HUSEMOEN GITTE NYSTRUP , DOLBERG JOHANNES , JENSEN KIM BIRKEBAEK , PETERSEN LENE , NOERREGAARD-MADSEN MADS , GODSKESEN MICHAEL ANDERS , GLAD SANNE SCHROEDER , NEVE SOEREN , THISTED THOMAS , KRONBORG TINE TITILOLA AKINLEM , SAMS CHRISTIAN , FELDING JAKOB , FRESKGAARD PER-OLA , GOULIAEV ALEX HAAHR , PEDERSEN HENRIK
发明人： FRANCH THOMAS , LUNDORF MIKKEL DYBRO , JAKOBSEN SOEREN NYBOE , OLSEN EVA KAMPMANN , ANDERSEN ANNE LEE , HOLTMANN ANETTE , HANSEN ANDERS HOLM , SOERENSEN ANDERS MALLING , GOLDBECH ANNE , DE LEON DAEN , KALDOR DITTE KIVSMOSE , SLOEK FRANK ABILGAARD , HUSEMOEN GITTE NYSTRUP , DOLBERG JOHANNES , JENSEN KIM BIRKEBAEK , PETERSEN LENE , NOERREGAARD-MADSEN MADS , GODSKESEN MICHAEL ANDERS , GLAD SANNE SCHROEDER , NEVE SOEREN , THISTED THOMAS , KRONBORG TINE TITILOLA AKINLEM , SAMS CHRISTIAN , FELDING JAKOB , FRESKGAARD PER-OLA , GOULIAEV ALEX HAAHR , PEDERSEN HENRIK
IPC分类号： C12N15/10 , C12Q1/68 , C40B40/06 , C40B50/06
CPC分类号： C12N15/1068 , C12N15/1089 , C40B40/08 , C40B50/04 , C40B50/06
摘要： Disclosed is a method for obtaining a bifunctional complex comprising a molecule linked to a single stranded identifier oligonucleotide, wherein a nascent bifunctional complex comprising a chemical reaction site and a priming site for enzymatic addition of a tag is a) reacted at the chemical reaction site with one or more reactants, and b) reacted enzymatically at the priming site with one or more tag(s) identifying the reactant(s).
摘要翻译：公开了一种获得包含与单链标识符寡核苷酸连接的分子的双功能复合物的方法，其中包含化学反应位点的新生双功能复合物和用于酶标添加的引发位点是a）在化学反应位点与一种或多种反应物，和b）在起始位点用一种或多种标记反应物的标签进行酶促反应。

2. 发明申请

WO2004039825A3 METHOD FOR THE SYNTHESIS OF A BIFUNCTIONAL COMPLEX 审中-公开
标题翻译：双功能复合物的合成方法
公开(公告)号：WO2004039825A3
公开(公告)日：2004-10-28
申请号：PCT/DK0300739
申请日：2003-10-30
申请人： NUEVOLUTION AS , FRESKGAARD PER-OLA , FRANCH THOMAS , GOULIAEV ALEX HAAHR , LUNDORF MIKKEL DYBRO , FELDING JAKOB , OLSEN EVA KAMPMANN , HOLTMANN ANETTE , JAKOBSEN SOEREN NYBOE , SAMS CHRISTIAN , GLAD SANNE SCHROEDER , JENSEN KIM BIRKEBAEK , PEDERSEN HENRIK
发明人： FRESKGAARD PER-OLA , FRANCH THOMAS , GOULIAEV ALEX HAAHR , LUNDORF MIKKEL DYBRO , FELDING JAKOB , OLSEN EVA KAMPMANN , HOLTMANN ANETTE , JAKOBSEN SOEREN NYBOE , SAMS CHRISTIAN , GLAD SANNE SCHROEDER , JENSEN KIM BIRKEBAEK , PEDERSEN HENRIK
IPC分类号： C12N15/10 , C12P19/34 , C07B61/00
CPC分类号： C12N15/1065 , C12N15/1068 , C12Q1/6806 , C12Q2521/101 , C12Q2521/501 , C40B50/10 , C40B50/16
摘要： A method for synthesising a bifunctional complex which comprises a reaction product and an encoding region. The complex is a hybridisation product between a nascent bifunctional complex and a building block. The nascent bifunctional complex comprises an attachment entity linked to an oligonucleotide identifier region and the building block comprises a fuctional entity attached to an oligonucleotide which is sufficiently complementary to the identifier region to allow for hybridisation . The functional entity may then be transferred to the attachment entity by a chemical reaction.The complementary identifier region further comprises a unique codon, which identifies the functional entity unequivocally. This codon functions as a template for forming a unique codon as an extention of the identifier region by use of an enzime, such as a polymerase. The unique codon may be used to decode the synthetic history of the reaction product after several cycles of transfer of functional entities.
摘要翻译：一种合成双功能复合物的方法，其包括反应产物和编码区。该复合物是新生的双功能复合物和构建块之间的杂交产物。新生的双功能复合物包含与寡核苷酸识别器区域连接的连接实体，并且构建单元包含连接于寡核苷酸的功能实体，其与识别符区域充分互补以允许杂交。然后可以通过化学反应将功能实体转移到附着实体。补充标识符区域还包括唯一的密码子，其明确地标识功能实体。该密码子用作用于通过使用酶，如聚合酶形成唯一密码子作为标识符区域扩展的模板。独特的密码子可以用于在功能实体的几个转移周期之后解码反应产物的合成历史。

3. 发明申请

WO03078445A2 A BUILDING BLOCK FORMING A C=C DOUBLE BOND UPON REACTION 审中-公开
标题翻译：一个建立块形成一个C = C双重绑定反应
公开(公告)号：WO03078445A2
公开(公告)日：2003-09-25
申请号：PCT/DK0300173
申请日：2003-03-14
申请人： NUEVOLUTION AS , GOULIAEV ALEX HAAHR , PEDERSEN HENRIK , GODSKESEN MICHAEL ANDERS , KRONBORG TINE TITILOLA AKINLEM , HUSEMOEN GITTE NYSTRUP , HO JUSTIN , FELDING JAKOB , SAMS CHRISTIAN
发明人： GOULIAEV ALEX HAAHR , PEDERSEN HENRIK , GODSKESEN MICHAEL ANDERS , KRONBORG TINE TITILOLA AKINLEM , HUSEMOEN GITTE NYSTRUP , HO JUSTIN , FELDING JAKOB , SAMS CHRISTIAN
IPC分类号： C07B61/00 , C07D405/04 , C07H21/00 , C12N15/10
CPC分类号： C07D405/04 , C07H21/00 , C12N15/1068 , C40B40/00
摘要： A building block having the dual capabilities of recognising an encoding element and transferring a Functional Entity Precursor to a recipient reactive group is disclosed. The building block may be used in the generation of a single complex or libraries of different complexes, wherein the complex comprises an encoded molecule linked to an encoding element. Libraries of complexes are useful in the quest for pharmaceutically active compounds.
摘要翻译：公开了具有识别编码元件并将功能实体前体传送到接收者反应组的双重能力的构建块。构建单元可以用于生成单个复合体或不同复合物的文库，其中复合物包含与编码元件连接的编码分子。复合物库可用于寻求药物活性化合物。

4. 发明申请

WO2004074429A3 METHOD FOR PRODUCING SECOND-GENERATION LIBRARY 审中-公开
标题翻译：生成第二代库的方法
公开(公告)号：WO2004074429A3
公开(公告)日：2004-09-30
申请号：PCT/DK2004000117
申请日：2004-02-23
申请人： NUEVOLUTION AS , FRESKGAARD PER-OLA , GOULIAEV ALEX HAAHR , THISTED THOMAS , OLSEN EVA KAMPMANN
发明人： FRESKGAARD PER-OLA , GOULIAEV ALEX HAAHR , THISTED THOMAS , OLSEN EVA KAMPMANN
IPC分类号： C12N15/10 , C12Q1/68 , C07B61/00 , C12P1/00
CPC分类号： C40B40/08 , B01J19/0046 , B01J2219/00592 , C12N15/1068 , C12Q1/6811 , C40B50/04 , C40B50/06 , C40B50/10 , C12Q2565/501 , C12Q2531/113
摘要： The present invention relates to a method for generating a second-generation library. In a first step, a library of encoded molecules associated with an identifier nucleic acid comprising codons identifying chemical entities that have participated in the formation of the encoded molecule is provided. In a second step, the library is partitioned and encoded molecules having a certain property are selected. Codons of identifiers of selected encoded molecules are subsequently identified, and a second-generation library is prepared using at least some of the chemical entities coded for by the identified codons. The new focussed library may be used for another partition step to select encoded molecules with a certain property.
摘要翻译：本发明涉及用于生成第二代库的方法。在第一步中，提供了与识别核酸相关的编码分子文库，其包含识别已参与编码分子形成的化学实体的密码子。第二步，将文库分区并选择具有某种特性的编码分子。随后鉴定所选编码分子的标识符密码子，并使用至少一些由所鉴定的密码子编码的化学实体制备第二代文库。新聚焦库可用于另一个分区步骤来选择具有某种属性的编码分子。

5. 发明申请

WO2004056994A3 QUASIRANDOM STRUCTURE AND FUNCTION GUIDED SYNTHESIS METHODS 审中-公开
标题翻译：准共形结构和功能指导综合方法
公开(公告)号：WO2004056994A3
公开(公告)日：2004-08-12
申请号：PCT/DK0300921
申请日：2003-12-19
申请人： NUEVOLUTION AS , GOULIAEV ALEX HAAHR , HOLTMANN ANETTE , PEDERSEN HENRIK , FRANCH THOMAS
发明人： GOULIAEV ALEX HAAHR , HOLTMANN ANETTE , PEDERSEN HENRIK , FRANCH THOMAS
IPC分类号： C12N15/10 , C07B61/00 , C07K1/04 , C12P1/00 , C12Q1/68
CPC分类号： C40B30/04 , C12N15/1068 , C40B20/04 , C40B40/06 , C40B50/04 , C40B50/08 , Y10T436/145555
摘要： The present invention is directed to the synthesis of molecules guided b connector polynucleotides (CPNs capable of hybridizing to complementory connector ploynucleotides (CCPNs) harbouring at least one functional entity comprising at least one reactive group. At least one of said CCPNs capable of hybridize to at least two CPNs. Each CPN will "call" for one or more CCPNs capable of hybridization to the CPN. Following the formation of a supramolecular hybridization complex comprising a plurality of CPNs and a plurality of CCPNs, the reaction of functional entity reactive groups result I the formation of a molecule comprising covalently linked functional entities. The formation of the molecule involves the transfer of functional entities from one or more "donor CCPNs" to at least on "acceptor CCPN" with which the transferred functional entities were not associated prior to the transfer.
摘要翻译：本发明涉及合成分子引导的b连接多核苷酸（能够与互补连接体多核苷酸（CCPN）杂交的CPN，所述互补连接体多核苷酸携带至少一个包含至少一个反应性基团的功能实体，至少一个所述CCPN能够与至少两个CPN，每个CPN将“呼叫”一个或多个能够与CPN杂交的CCPN，形成包含多个CPN和多个CCPN的超分子杂交复合物后，功能实体反应基团的反应导致I 形成包含共价连接的功能实体的分子，分子的形成涉及将功能实体从一个或多个“供体CCPN”转移到至少一个“受体CCPN”上，转让。

6. 发明申请

WO2004083427A3 LIGATIONAL ENCODING OF SMALL MOLECULES 审中-公开
标题翻译：小分子的编码
公开(公告)号：WO2004083427A3
公开(公告)日：2005-02-17
申请号：PCT/DK2004000195
申请日：2004-03-22
申请人： NUEVOLUTION AS , FRANCH THOMAS , JACOBSEN SOEREN NYBOE , RASMUSSEN TORBEN , NEVE SOEREN , PEDERSEN HENRIK , GOULIAEV ALEX HAAHR
发明人： FRANCH THOMAS , JACOBSEN SOEREN NYBOE , RASMUSSEN TORBEN , NEVE SOEREN , PEDERSEN HENRIK , GOULIAEV ALEX HAAHR
IPC分类号： C12N15/10 , C12P21/02
CPC分类号： C07H21/04 , C12N15/1068 , C12P21/02 , C40B40/06 , C40B50/04
摘要： The invention relates to a method for synthesising a bifunctional complex comprising an encoded molecule and an identifier polynucleotide identifying the chemical entities having participated in the synthesis of the encoded molecule, said method comprising the steps of i) providing a) at least one template comprising one or more codons capable of hybridising to an anti-codon, wherein said template is optionally associated with one or more chemical entities, and b) a plurality of building blocks each comprising an anti-codon associated with one or more chemical entities, and ii) hybridising the anti-codon of one or more of the provided building blocks to the template, iii) covalently linking said anti-codons and/or linking the at least one template with the anti-codon of at least one building block, thereby generating an identifier polynucleotide capable of identifying chemical entities having participated in the synthesis of the encoded molecule, iv) separating the template from one or more of the anti-codons hybridised thereto, thereby generating an at least partly single stranded identifier polynucleotide associated with a plurality of chemical entities, v) generating a bifunctional complex comprising an encoded molecule and an identifier polynucleotide identifying the chemical entities having participated in the synthesis of the encoded molecule, wherein said encoded molecule is generated by reacting at least two of said plurality of chemical entities associated with the identifier polynucleotide, and wherein said at least two chemical entities are provided by separate building blocks.
摘要翻译：本发明涉及一种合成双功能复合物的方法，所述双功能复合物包含编码分子和识别已经参与编码分子合成的化学实体的标识多核苷酸，所述方法包括以下步骤：i）提供a）至少一个包含一个或更多能够与抗密码子杂交的密码子，其中所述模板任选地与一个或多个化学实体相关联，以及b）多个结构单元，每个结构单元包含与一个或多个化学实体相关联的抗密码子，和ii）将一个或多个所提供的构建块的抗密码子与模板杂交，iii）共价连接所述抗密码子和/或将至少一个模板与至少一个构建块的抗密码子连接，由此产生能够识别已经参与编码分子的合成的化学实体的标识符多核苷酸，iv）将模板从一个或多个分离出来更多的与其杂交的抗密码子，从而产生与多个化学实体相关联的至少部分单链标识多核苷酸，v）产生包含编码分子的双功能复合物和识别参与合成的化学实体的标识符多核苷酸的编码分子，其中所述编码的分子通过使与所述标识多核苷酸相关联的所述多个化学实体中的至少两个反应而产生，并且其中所述至少两个化学实体由单独的构建块提供。

7. 发明申请

WO2011127933A1 BI-FUNCTIONAL COMPLEXES AND METHODS FOR MAKING AND USING SUCH COMPLEXES 审中-公开
标题翻译：双功能复合物和制备和使用这种复合物的方法
公开(公告)号：WO2011127933A1
公开(公告)日：2011-10-20
申请号：PCT/DK2011000031
申请日：2011-04-16
申请人： NUEVOLUTION AS , GOULIAEV ALEX HAAHR , FRANCH THOMAS , GODSKESEN MICHAEL ANDERS , JENSEN KIM BIRKEVAEK
发明人： GOULIAEV ALEX HAAHR , FRANCH THOMAS , GODSKESEN MICHAEL ANDERS , JENSEN KIM BIRKEVAEK
IPC分类号： C12N15/10
CPC分类号： C12N15/1065 , C12N15/1068
摘要： The present invention is directed to a method for the synthesis of a bi-functional complex comprising a molecule part and an identifier oligonucleotide part identifying the molecule part. A part of the synthesis method according to the present invention is preferably conducted in one or more organic solvents when a nascent bi-functional complex comprising an optionally protected tag or oligonucleotide identifier is linked to a solid support, and another part of the synthesis method is preferably conducted under conditions suitable for enzymatic addition of an oligonucleotide tag to a nascent bi-functional complex in solution.
摘要翻译：本发明涉及一种双官能复合物的合成方法，其包括分子部分和识别分子部分的识别寡核苷酸部分。当包含任选保护的标签或寡核苷酸识别符的新生双功能复合物与固体支持物连接时，根据本发明的合成方法的一部分优选在一种或多种有机溶剂中进行，另一部分合成方法为优选在适合于向溶液中的新生双功能复合物酶促添加寡核苷酸标签的条件下进行。

8. 发明申请

WO2005090566A3 LIGATIONAL ENCODING USING BUILDING BLOCK OLIGONUCLEOTIDES 审中-公开
标题翻译：使用建筑物块编码的编码
公开(公告)号：WO2005090566A3
公开(公告)日：2006-03-09
申请号：PCT/DK2005000199
申请日：2005-03-22
申请人： NUEVOLUTION AS , GOULIAEV ALEX HAAHR , PEDERSEN HENRIK
发明人： GOULIAEV ALEX HAAHR , PEDERSEN HENRIK
IPC分类号： C12N15/10 , C12P7/62 , C12P13/02 , C12P19/04 , C12P19/34 , C12P21/02
CPC分类号： C12N15/1068
摘要： The present invention in one aspect relates to a method for synthesizing a bifunctional complex comprising a molecule and an identifier polynucleotide identifying at least some of the chemical entities which have participated in the synthesis of the molecule in accordance with the methods of the present invention. The invention also relates to a library of different bifunctional complexes. The library of the invention can be used e.g. for identifying drug leads. Furthermore, the present invention is based on the principle that chemical entities initially provided on a building block oligonucleotide (i.e. a building block having an oligonucleotide part which is linked to a chemical entity) can be brought into reactive proximity without the use of a template comprising a set of covalently linked codons. Also, the present invention allows reaction of chemical entities when the chemical entities are linked to a single stranded identifier polynucleotide obtained by covalently linking the oligonucleotide parts (oligonucleotide identifiers) of the building blocks. The single stranded identifier polynucleotides differs from template directed synthesis methods employing codon and anti-codon hybridisation between a template and one or more transfer units, i.e. methods wherein e.g. reactive units on transfer units are reacted while the anti-codon of the transfer units are hybridised to template codons.
摘要翻译：本发明一方面涉及一种用于合成双功能复合物的方法，所述双功能复合物包含分子和标识物多核苷酸，其鉴定了根据本发明的方法参与分子合成的至少一些化学实体。本发明还涉及不同双功能复合物的文库。本发明的文库可以例如使用。用于鉴定药物的潜在客户。此外，本发明是基于以下原则：最初提供在构建单元寡核苷酸上的化学实体（即具有与化学实体连接的寡核苷酸部分的构建单元）可以进行反应性接近而不使用包含一套共价连锁的密码子。此外，当化学实体与通过共价连接构建单元的寡核苷酸部分（寡核苷酸标识符）获得的单链标识符多核苷酸连接时，本发明允许化学实体的反应。单链标识符多核苷酸与模板定向合成方法的不同之处在于使用模板和一个或多个转移单元之间的密码子和抗 - 密码子杂交，转移单元上的反应单元反应，同时转移单元的反密码子与模板密码子杂交。

9. 发明申请

WO9942456A3 NOVEL COMPOUNDS AND THEIR USE AS POSITIVE AMPA RECEPTOR MODULATORS 审中-公开
标题翻译：新型化合物及其作为阳性AMPA受体调节剂的应用
公开(公告)号：WO9942456A3
公开(公告)日：1999-10-07
申请号：PCT/DK9900070
申请日：1999-02-18
申请人： NEUROSEARCH AS , GOULIAEV ALEX HAAHR , LARSEN MOGENS , VARMING THOMAS , MATHIESEN CLAUS , JOHANSEN TINA HOLM , SCHEEL KRUEGER JOERGEN , OLSEN GUNNAR M , NIELSEN ELSEBET OESTERGAARD
发明人： GOULIAEV ALEX HAAHR , LARSEN MOGENS , VARMING THOMAS , MATHIESEN CLAUS , JOHANSEN TINA HOLM , SCHEEL-KRUEGER JOERGEN , OLSEN GUNNAR M , NIELSEN ELSEBET OESTERGAARD
IPC分类号： C07D239/74 , A61K31/18 , A61K31/517 , A61K31/535 , A61K31/536 , A61K31/5415 , A61K31/549 , A61K31/554 , A61P9/10 , A61P25/00 , A61P25/08 , A61P25/14 , A61P25/18 , A61P25/24 , A61P25/28 , A61P25/30 , A61P25/32 , A61P25/36 , A61P43/00 , C07C311/37 , C07C311/39 , C07D239/88 , C07D239/90 , C07D239/91 , C07D265/22 , C07D285/24 , C07D285/28 , C07D285/32 , C07D285/36 , C07D417/04 , C07D417/10 , C07D417/12 , C07D513/04 , A61K31/505 , A61K31/54 , C07D401/04 , C07D403/04 , C07D405/04 , C07D409/04 , C07D413/04
CPC分类号： C07D417/04 , C07D239/90 , C07D285/24 , C07D285/28 , C07D513/04
摘要： The invention provides novel compounds represented by general formula (I) wherein the bond represented by the broken line may be a single, double bond or absent; and if the bond is absent, then the nitrogen is substituted with a hydrogen and R ; X represents SO2 or C=O of CH2; Y represents -CH(R )-, -N(R )- or -N(R )-CH2-, O; and the meaning of R , R , R , R , R , R , and R are as defined in the application. The compounds are useful as positive modulators of the AMPA-receptor.
摘要翻译：本发明提供了由通式（I）表示的新化合物，其中由虚线表示的键可以是单键，双键或不存在; 如果该键不存在，则该氮被氢和R 2取代; X代表CH 2的SO 2或C = O; Y代表-CH（R 4） - ， - N（R 4） - 或-N（R 4）-CH 2 - ，O; 并且R 2，R 3，R 4，R 5，R 6，R 7和R 8的含义如本申请中所定义。该化合物可用作AMPA受体的正调节剂。

10. 发明申请

WO9967218A2 METHOD OF PREPARING 5- OR 8-BROMOISOQUINOLINE DERIVATIVES 审中-公开
标题翻译：制备5-或8-溴代喹啉衍生物的方法
公开(公告)号：WO9967218A2
公开(公告)日：1999-12-29
申请号：PCT/DK9900347
申请日：1999-06-22
申请人： NEUROSEARCH AS , GOULIAEV ALEX HAAHR , HANSEN WILLIAM
发明人： GOULIAEV ALEX HAAHR , HANSEN WILLIAM
IPC分类号： C07D217/02 , C07D217/00
CPC分类号： C07D217/02
摘要： The invention describes a novel process for the preparation of 5- or 8-bromoisoquinoline from isoquinoline. The process gives high yields and is suitable for large scale work.
摘要翻译：本发明描述了用于从异喹啉制备5-或8-溴异喹啉的新方法。该方法产量高，适用于大规模工作。

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