公开(公告)号：US10112953B2

公开(公告)日：2018-10-30

申请号：US15283187

申请日：2016-09-30

申请人： SITEONE THERAPEUTICS, INC. ,  THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY

发明人： John Mulcahy ,  Hassan Pajouhesh ,  Grant Masaaki Shibuya ,  Anton Delwig ,  George Miljanich ,  Justin Du Bois

IPC分类号： C07D487/14

摘要： Provided herein are compounds, pharmaceutical compositions comprising the compounds, methods of preparing the compounds, and methods of using the compounds and compositions in treating conditions associated with voltage-gated sodium channel function where the compounds are 11,13-modified saxitoxins according to Formula (I): where R1, X1 and X3 are as described herein.

公开(公告)号：US11236097B2

公开(公告)日：2022-02-01

申请号：US16499205

申请日：2018-03-29

申请人： SITEONE THERAPEUTICS, INC. ,  THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY

发明人： John Mulcahy ,  Hassan Pajouhesh ,  George Miljanich ,  Anton Delwig ,  Jacob Beckley ,  Grant Masaaki Shibuya ,  Justin Du Bois

IPC分类号： C07D487/14

摘要： Provided herein are compounds, pharmaceutical compositions comprising the compounds, methods of preparing the compounds, and methods of using the compounds and compositions in treating conditions associated with voltage-gated sodium channel function where the compounds are 11,13-modified saxitoxins according to Formula (I): where R4, R4a, R7, R7a, and X2 are as described herein.

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.

公开(公告)号：US11834456B2

公开(公告)日：2023-12-05

申请号：US17585530

申请日：2022-01-26

申请人： SITEONE THERAPEUTICS, INC. ,  THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY

发明人： John Mulcahy ,  Hassan Pajouhesh ,  George Miljanich ,  Anton Delwig ,  Jacob Beckley ,  Grant Masaaki Shibuya ,  Justin Du Bois

IPC分类号： C07D487/14

CPC分类号： C07D487/14

摘要： Provided herein are compounds, pharmaceutical compositions comprising the compounds, methods of preparing the compounds, and methods of using the compounds and compositions in treating conditions associated with voltage-gated sodium channel function where the compounds are 11,13-modified saxitoxins according to Formula (I): where R4, R4a, R7, R7a, and X2 are as described herein.

公开(公告)号：US20220259218A1

公开(公告)日：2022-08-18

申请号：US17585530

申请日：2022-01-26

申请人： SITEONE THERAPEUTICS, INC. ,  THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY

发明人： John Mulcahy ,  Hassan Pajouhesh ,  George Miljanich ,  Anton Delwig ,  Jacob Beckley ,  Grant Masaaki Shibuya ,  Justin Du Bois

IPC分类号： C07D487/14

摘要： Provided herein are compounds, pharmaceutical compositions comprising the compounds, methods of preparing the compounds, and methods of using the compounds and compositions in treating conditions associated with voltage-gated sodium channel function where the compounds are 11,13-modified saxitoxins according to Formula (I): where R4, R4a, R7, R7a, and X2 are as described herein.

公开(公告)号：US11279706B2

公开(公告)日：2022-03-22

申请号：US16499201

申请日：2018-03-29

申请人： SITEONE THERAPEUTICS, INC. ,  THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY

发明人： John Mulcahy ,  Hassan Pajouhesh ,  George Miljanich ,  Anton Delwig ,  Jacob Beckley ,  Grant Masaaki Shibuya ,  Justin Du Bois

IPC分类号： C07D487/14 ,  A61P29/00

摘要： Provided herein are compounds, pharmaceutical compositions comprising the compounds, methods of preparing the compounds, and methods of using the compounds and compositions in treating conditions associated with voltage-gated sodium channel function where the compounds are 11,13-modified saxitoxins according to Formula (I): where R1, X1, and X2 are as described herein.

公开(公告)号：US10106549B2

公开(公告)日：2018-10-23

申请号：US15302964

申请日：2015-04-09

申请人： SITEONE THERAPEUTICS, INC. ,  THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY

发明人： Hassan Pajouhesh ,  George Miljanich ,  John Mulcahy ,  Justin Du Bois ,  Matthew Axtman ,  James Walker ,  Jeffrey E. Merit

IPC分类号： C07D487/14

摘要： Provided herein are compounds, pharmaceutical compositions comprising the compounds, and methods of using the compounds and compositions in treating conditions associated with voltage-gated sodium channel function, for example conditions associated with pain. The compounds are 10′,11′-modified saxitoxins. The compounds are optionally additionally modified at carbon 13. In certain embodiments, the 10′,11′-modified saxitoxins are of Formula I: where R1, R2 and R3 are as described herein. Also provided herein are methods of treating pain in a mammal comprising administering an effective treatment amount of a 10′,11′ modified saxitoxin or composition to a mammal. In an embodiment, the mammal is a human.