公开(公告)号：EP3125943A1

公开(公告)日：2017-02-08

申请号：EP15773458.3

申请日：2015-03-30

申请人： Merck Sharp & Dohme Corp. ,  Ambrx, Inc.

发明人： GARBACCIO, Robert M. ,  KERN, Jeffrey ,  BRANDISH, Philip E. ,  SHAH, Sanjiv ,  LIANG, Linda ,  SUN, Ying ,  WANG, Jianing ,  KNUDSEN, Nick ,  BECK, Andrew ,  MANIBUSAN, Anthony ,  GATELY, Dennis

IPC分类号： A61K47/24

CPC分类号： C07K16/2866 ,  A61K47/6803 ,  A61K47/6817 ,  A61K47/6849 ,  A61K47/6889 ,  A61K51/1045 ,  C07F9/091 ,  C07F9/098 ,  C07F9/12 ,  C07F9/2458 ,  C07F9/5721 ,  C07F9/65517 ,  C07F9/65583 ,  C07F9/65586 ,  C07F9/6561 ,  C07H19/10

摘要： Phosphate-based linkers with tunable stability for intracellular delivery of drug conjugates are described. The phosphate-based linkers comprise a monophosphate, diphosphate, triphosphate, or tetraphosphate group (phosphate group) and a linker arm comprising a tuning element and optionally a spacer. A payload is covalently linked to the phosphate group at the distal end of the linker arm and the functional group at the proximal end of the linker arm is covalently linked to a cell-specific targeting ligand such as an antibody. These phosphate-based linkers have a differentiated and tunable stability in blood vs. an intracellular environment (e.g. lysosomal compartment).

摘要翻译： 描述了具有用于细胞内递送药物偶联物的可调节稳定性的磷酸酯接头。 基于磷酸盐的连接体包含单磷酸盐，二磷酸盐，三磷酸盐或四磷酸盐基团（磷酸酯基团）和包含调谐元件和任选的间隔基的连接臂。 有效载荷与连接臂末端的磷酸基团共价连接，并且连接臂近端的官能团与细胞特异性靶向配体如抗体共价连接。 这些基于磷酸酯的接头在血液中相对于细胞内环境（例如溶酶体隔室）具有分化和可调节的稳定性。

公开(公告)号：EP2704573A1

公开(公告)日：2014-03-12

申请号：EP12779437.8

申请日：2012-04-30

申请人： Merck Sharp & Dohme Corp.

发明人： BESHORE, Douglas C. ,  GARBACCIO, Robert M. ,  KUDUK, Scott D. ,  JOHNSON, Adam W. ,  SKUDLAREK, Jason, W.

IPC分类号： A01N43/64 ,  A01N43/82 ,  A61K31/41

CPC分类号： C07D413/12 ,  C07D249/18 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/10 ,  C07D413/10

摘要： The present invention is directed to aminomethyl biaryl benzotriazole derivatives which are potentiators of metabotropic glutamate receptors, particularly the mGluR2 receptor, and which are useful in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which metabotropic glutamate receptors are involved.