公开(公告)号：US07223837B2

公开(公告)日：2007-05-29

申请号：US10472921

申请日：2002-03-25

申请人： Franciscus Marinus Hendrikus De Groot ,  Patrick Henry Beusker ,  Johannes Wilhelm Scheeren ,  Dick De Vos ,  Leonardus Wilhelmus Adriaan Van Berkom ,  Guuske Frederike Busscher ,  Antoinette Eugenie Seelen ,  Ralph Koekkoek ,  Carsten Albrecht

发明人： Franciscus Marinus Hendrikus De Groot ,  Patrick Henry Beusker ,  Johannes Wilhelm Scheeren ,  Dick De Vos ,  Leonardus Wilhelmus Adriaan Van Berkom ,  Guuske Frederike Busscher ,  Antoinette Eugenie Seelen ,  Ralph Koekkoek ,  Carsten Albrecht

IPC分类号： C07K5/08

CPC分类号： B82Y5/00 ,  A61K47/65 ,  A61K47/67 ,  A61K47/6889 ,  A61K47/6899

摘要： This invention is directed to prodrugs that can be activated at the preferred site of action in order to selectively deliver the corresponding therapeutic parent drugs to target cells or to the target site. This invention will therefore primarily but not exclusively relate to tumor cells as target cells. More specifically the prodrugs are compounds of the formula V—(W)k—(X)l—A—Z, wherein: V is a specifier; (W)k—(X)l—A is an elongated self-elimination spacer system; W and X are each a 1,(4+2n) electronic cascade spacer, being the same or different; A is either a spacer group of formula (Y)m wherein: Y is a 1,(4+2n) electronic cascade spacer, or a group of formula U being a cyclization elimination spacer; Z is a therapeutic drug; k, l and m are integers from 0 (included) to 5 (included); n is an integer of 0 (included) to 10 (included), with the provisos that: —when A is (Y)m: k+l+m≧1, and if k+l+m=1; —when A is U: k+l≧1.

摘要翻译： 本发明涉及可以在优选的作用位点被活化的前药，以便选择性地将相应的治疗性母体药物递送至靶细胞或靶位点。 因此，本发明主要但不完全涉及作为靶细胞的肿瘤细胞。 更具体地，前药是式V-（W） - （X）1-Z-Z的化合物，其中：V是说明符; （W） - （X）1 - A是细长的自消除间隔体系; W和X分别为1（4 + 2n）个电子级联间隔物，相同或不同; A是式（Y）的间隔基团其中：Y是1，（4 + 2n）电子级联间隔基，或者是一组式U是环化消除间隔基; Z是治疗药物; k，l和m是从0（包括）到5（包括）的整数; n是0（包括）到10（包括）的整数，条件是：当A是（Y）m：k + 1 + m> = 1时，如果k + 1 + m = 1; - 当A是U：k + l> = 1。