公开(公告)号：EP2611927A1

公开(公告)日：2013-07-10

申请号：EP11822416.1

申请日：2011-08-29

申请人： Merck Sharp & Dohme Corp.

发明人： COLLETTI, Steven, L. ,  GOSSELIN, Francis ,  JADHAV, Vasant, R. ,  SHAW, Anthony, W. ,  TELLERS, David, M. ,  TUCKER, Thomas, J. ,  YUAN, Yu ,  ZEWGE, Daniel

IPC分类号： C12P21/06

CPC分类号： C12N15/113 ,  A61K47/64 ,  C12N15/111 ,  C12N15/87 ,  C12N2310/14 ,  C12N2310/3513 ,  C12N2310/3515 ,  C12N2320/32

摘要： In an embodiment the instant invention discloses a modular composition comprising 1) an oligonueleotide; 2) one or more linkers, which may be the same or different, selected from Table 1, wherein the linkers are attached to the oligonucleotide at the 2'-position of the ribose rings and/or the terminal 3'- and/or 5'-positions of the oligonucleotide; 3) optionally, one or more peptides, which may be the same or different, selected from SEQ ID NOs: 1-59, wherein the peptides are attached to the linkers; and optionally one or more lipids, solubilizing groups and/or targeting ligands attached to the oligonucleotide.

摘要翻译： 在一个实施方案中，本发明公开了一种模块化组合物，其包含1）寡核苷酸; 2）选自表1的一个或多个接头，其可以是相同或不同的，其中所述接头在核糖环的2'-位置和/或末端3'-和/或5'-位置与寡核苷酸连接 寡核苷酸的'位置; 3）任选地，选自SEQ ID NO：1-59的一种或多种可相同或不同的肽，其中所述肽连接于所述接头; 和任选地与寡核苷酸连接的一种或多种脂质，增溶基团和/或靶向配体。

公开(公告)号：EP2526113A1

公开(公告)日：2012-11-28

申请号：EP11735064.5

申请日：2011-01-19

申请人： Merck Sharp & Dohme Corp.

发明人： ZEWGE, Daniel ,  GOSSELIN, Francis

IPC分类号： C07H21/02

CPC分类号： C12N15/113 ,  C07C217/40 ,  C07C217/52 ,  C07C2601/02 ,  C07D207/08 ,  C07D207/12 ,  C07D209/48 ,  C07D211/22 ,  C07D211/44 ,  C07D211/46 ,  C07D295/088 ,  C07H21/02 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/141 ,  C12N2310/321 ,  C12N2330/30

摘要： This invention relates to the post-synthetic chemical modification of RNA at the 2'-position on the ribose ring via a copper catalyzed Huisgen cycloaddition ("click" chemistry: Kolb, Sharpless Drug Discovery Today 2003, 8, 1128). The invention 1) avoids complex, tedious multi-step syntheses of each desired modified ribonucleoside; 2) allows diverse chemical modifications using high-fidelity chemistry that is completely orthogonal to commonly used alkylamino, carboxylate and disulfide linker reactivities; 3) allows introduction of functional groups that are incompatible with modern automated solid-phase synthesis of RNA and subsequent cleavage-deprotection steps; 4) allows introduction of functional groups useful as targeting ligands; and 5) enables high-throughput structure-activity relationship studies on chemically modified RNA in 96-well format.

摘要翻译： 本发明涉及通过铜催化的Huisgen环加成在核糖环上2'-位上的RNA的后合成化学修饰（“click”chemistry：Kolb，Sharpless Drug Discovery Today 2003,8,1128）。 本发明1）避免了每种所需修饰的核糖核苷的复杂繁琐的多步合成; 2）允许使用与常用的烷基氨基，羧酸酯和二硫化物连接体反应性完全正交的高保真化学的不同化学修饰; 3）允许引入与现代自动化固相合成RNA和随后的切割 - 脱保护步骤不相容的官能团; 4）允许引入可用作靶向配体的官能团; 和5）能够对96孔格式的化学修饰RNA进行高通量结构 - 活性关系研究。

公开(公告)号：EP2203446A1

公开(公告)日：2010-07-07

申请号：EP08833922.1

申请日：2008-09-23

申请人： Merck Sharp & Dohme Corp.

发明人： GOSSELIN, Francis ,  VYDRA, Vicky

IPC分类号： C07D413/12 ,  A61K31/4245 ,  A61P19/02

CPC分类号： C07D413/12

摘要： This invention provides novel salt and crystalline forms thereof of (-) 4-(4-fluorophenyl)-7-[({5-[1-hydroxy-1-(trifluoromethyl)propyl]-1,3,4-oxadiazol-2-yl}-amino)-methyl]-2H-chromen-2-one. The compounds are 5-LO inhibitors and are useful for treatment of conditions such as asthma, allergic rhinitis, COPD, and atherosclerosis.