公开(公告)号：US10513525B2

公开(公告)日：2019-12-24

申请号：US14923349

申请日：2015-10-26

申请人： THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY

发明人： Justin Du Bois ,  John Mulcahy ,  Brian Andresen ,  David C. Yeomans ,  Sandip Biswal

IPC分类号： A61K31/519 ,  C07D487/16 ,  C07D487/14 ,  A61K8/49 ,  A61K49/00 ,  A61Q19/02 ,  A61Q19/08 ,  A61K51/04

摘要： Saxitoxin analogue compounds, compositions, pharmaceutical compositions, methods of synthesis of saxitoxin analogues, methods of imaging, methods of treatment, including methods of treating pain, are provided. Saxitoxin (STX), gonyautoxin (GTX), and zetekitoxin, and variant STX compounds bind to sodium channels and are effective to reduce or block flow of sodium ions through such channels. Such channel block affects nerve and muscle action, and may be effective to reduce or block pain sensations, relax muscles, reduce muscle spasm, and reduce wrinkles. STX analogue binding to sodium channels may also be useful to locate, image, or mark sodium channels, and so be useful in studying sodium channels and sodium channel disorders, and in the diagnosis and treatment of patients suffering from sodium channel disorders. In embodiments, the variant STX compounds include conjugates having increased serum half-life as compared to STX when administered to a subject. Also provided are methods for alleviating pain in a subject in need of treatment.