公开(公告)号：US6107489A

公开(公告)日：2000-08-22

申请号：US267274

申请日：1999-03-12

申请人： Alexander Krantz ,  Dominique Blanchard ,  Diane DeNagel ,  Yonghong Song

发明人： Alexander Krantz ,  Dominique Blanchard ,  Diane DeNagel ,  Yonghong Song

IPC分类号： C07D233/54 ,  A61K38/05

CPC分类号： C07D233/64

摘要： Novel compounds comprising chemically reactive intermediates which can react with available reactive functionalities on blood components to form covalent linkages, where the resulting covalently-bound conjugates are found to have renin inhibition activity are provided. Specifically, the renin inhibitor compounds of the present invention are tripeptide derivatives of a known renin inhibitor which can be covalently linked to chemically reactive functionalities on various blood components. The conjugated renin inhibitors thereby have extended lifetimes in the bloodstream, as compared to the unconjugated parent drug, and are, therefore, capable of maintaining renin inhibitory activity for extended periods of time as compared to the unconjugated parent drug. Also provided herein are methods for inhibiting renin activity in vivo comprising administering to the bloodstream of a mammalian host the novel compounds of the present invention.

摘要翻译： 提供了包含化学反应中间体的新型化合物，其可以与血液成分上的可用反应性官能团反应以形成共价键，其中发现所得的共价结合的缀合物具有肾素抑制活性。 具体地说，本发明的肾素抑制剂化合物是可以与各种血液成分上的化学反应性官能团共价连接的已知的肾素抑制剂的三肽衍生物。 与非共轭母体药物相比，缀合的肾素抑制剂在血液中的寿命延长，因此与未缀合的母体药物相比，能够延长延长的时间段内的肾素抑制活性。 本文还提供了用于在体内抑制肾素活性的方法，包括向哺乳动物宿主的血流施用本发明的新化合物。