利索-全球专利检索

  1. 登录
  2. 注册

搜索结果

8 条记录 (耗时 0.03 秒)

    METHODS OF USING MONOMETHYLVALINE COMPOSITIONS HAVING PHENYLALANINE CARBOXY MODIFICATIONS AT THE C-TERMINUS
    2.
    发明申请
    METHODS OF USING MONOMETHYLVALINE COMPOSITIONS HAVING PHENYLALANINE CARBOXY MODIFICATIONS AT THE C-TERMINUS 审中-公开
    在C-末端使用具有苯乙胺羧酸改性的单甲基异喹啉组合物的方法

    公开(公告)号：US20150044238A1

    公开(公告)日：2015-02-12

    申请号：US14502210

    申请日：2014-09-30

    申请人： Seattle Genetics, Inc.

    发明人： Svetlana O Doronina ,  Toni Beth Kline ,  Scott Jeffrey ,  Peter D Senter ,  Damon Meyer

    IPC分类号： A61K47/48 ,  A61K39/395 ,  C07K16/28

    CPC分类号： A61K47/48415 ,  A61K38/00 ,  A61K39/3955 ,  A61K47/6811 ,  A61K2039/505 ,  C07K5/0205 ,  C07K7/02 ,  C07K16/2866 ,  C07K2317/76 ,  Y02A50/40 ,  Y02A50/401 ,  Y02A50/406 ,  Y02A50/48

    摘要： Auristatin peptide analogs of MeVal-Val-Dil-Dap-Phe (MMAF) having a carboxylic acid equivalent at the C-terminal phenylalanine were prepared and attached to ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand-drug conjugates were active in vitro and in vivo in inhibiting cell proliferation and are represented by the general structure of Lv-[(LU)0-1-(D)1-4]p wherein L- is Ligand unit; LU is a Linker unit (LU); v is 1; p is an number ranging from about 1 to about 20; and D is a drug moiety having the formula: wherein the moiety —N(R9)Z1 is a phenylalanine bioisostere, wherein Z1 is —CH(R10)Z2 so that the phenylalanine bioisostere has the structure of Formula A: and wherein the substituents R2-R10, X1 and Z2 are as defined.

    摘要翻译： 制备具有C-末端苯丙氨酸羧酸当量的MeVal-Val-Dil-Dap-Phe（MMAF）的Auristatin肽类似物，并通过各种接头包括马来酰亚氨基己酰基val-cit-PAB连接到配体上。 所得配体 - 药物偶联物在体外和体内在抑制细胞增殖中是活性的，并且由Lv- [（LU）0-1-（D）1-4] p的一般结构表示，其中L-是配体单元; LU是一个链接器单元（LU）; v为1; p为约1至约20的数; 并且D是具有下式的药物部分：其中部分-N（R 9）Z 1是苯丙氨酸生物电子等排体，其中Z 1是-CH（R 10）Z 2，使得苯丙氨酸生物电子等排体具有式A的结构：并且其中取代基R 2 -R10，X1和Z2如上所定义。