公开(公告)号：US09586880B2

公开(公告)日：2017-03-07

申请号：US14033176

申请日：2013-09-20

申请人： President and Fellows of Harvard College

发明人： Junying Yuan ,  Emily P. Hsu

IPC分类号： C07D233/02 ,  C07C35/37 ,  C07D209/08 ,  C07D211/90 ,  C07D215/08 ,  C07D231/06 ,  C07D231/12 ,  C07D231/56 ,  C07D277/46 ,  C07D307/52 ,  C07D333/20 ,  C07D403/06 ,  C07D403/12 ,  C07D405/06 ,  C07D417/12 ,  C07D495/04 ,  C07D498/08 ,  C07C33/38 ,  C07D211/78 ,  C07D277/18

CPC分类号： C07C35/37 ,  C07C33/38 ,  C07D209/08 ,  C07D211/78 ,  C07D211/90 ,  C07D215/08 ,  C07D231/06 ,  C07D231/12 ,  C07D231/56 ,  C07D233/02 ,  C07D277/18 ,  C07D277/46 ,  C07D307/52 ,  C07D333/20 ,  C07D403/06 ,  C07D403/12 ,  C07D405/06 ,  C07D417/12 ,  C07D495/04 ,  C07D498/08

摘要： Compounds having the following structure (VI-A): or any pharmaceutically acceptable salt or solvate thereof, or any stereoisomer thereof, wherein RE1, RE2, RE3, RE4, ZE2 and ZE3 are as disclosed herein, are provided. Pharmaceutical compositions comprising the compounds, and methods for use of the compounds for treating disorders associated with necrosptosis are also provided.

摘要翻译： 本发明特征在于一系列杂环衍生物，其抑制肿瘤坏死因子α（TNF-α）诱导的人工坏死。 本发明的杂环化合物由式（I） - （VIII）和化合物（I） - （I），（13） - （26），（27） - （33），（48） - （57 ），（58） - （70）。 这些死亡细胞被证明能抑制人类Jurkat T细胞的FADD缺陷型变体中的TNF-诱导的人工死亡。 本发明还特征在于具有硫酸霜霉素的药物组合物。 本发明的化合物和组合物也可以用于治疗棘球菌根可能起重要作用的病症。

公开(公告)号：US20170050929A1

公开(公告)日：2017-02-23

申请号：US15248843

申请日：2016-08-26

申请人： President and Fellows of Harvard College ,  Shanghai Institute of Organic Chemistry

发明人： Junying Yuan ,  Dawei Ma ,  Lihong Zhang

IPC分类号： C07D211/44 ,  C07D401/12 ,  C07D491/22 ,  C07D211/82

CPC分类号： C07D211/44 ,  A61K31/445 ,  C07D211/82 ,  C07D401/12 ,  C07D491/22

摘要： This invention pertains to screening methods for identifying autophagy inducing compounds.

摘要翻译： 本发明涉及鉴定自噬诱导化合物的筛选方法。

公开(公告)号：US20160304498A1

公开(公告)日：2016-10-20

申请号：US15194413

申请日：2016-06-27

申请人： President and Fellows of Harvard College ,  Shanghai Institute of Organic Chemistry,

发明人： Junying Yuan ,  Yijun Zhou ,  Shan Qian ,  Dawei Ma

IPC分类号： C07D403/06

CPC分类号： C07D403/06 ,  A61P9/10 ,  A61P29/00 ,  C07D233/78

摘要： A compound having the following structure (I): or a pharmaceutically acceptable salt, prodrug, stereoisomer or tautomer thereof, is provided. Related compounds, methods for preparation of the same and uses of the compounds for treatment of various indications, including treatment of necrotic cell diseases and/or inflammation, are also provided.

摘要翻译： 或其药学上可接受的盐，前药，立体异构体或互变异构体。 还提供了相关化合物，其制备方法和用于治疗各种适应症的化合物的用途，包括治疗坏死性细胞疾病和/或炎症。

公开(公告)号：US09108955B2

公开(公告)日：2015-08-18

申请号：US14152703

申请日：2014-01-10

申请人： President and Fellows of Harvard College ,  Tufts University ,  THE BRIGHAM AND WOMEN'S HOSPITAL, INC. ,  TRUSTEES OF BOSTON UNIVERSITY

发明人： Gregory D. Cuny ,  Xin Teng ,  Junying Yuan ,  Alexei Degterev ,  John A. Porco, Jr.

IPC分类号： C07D285/06 ,  C07D417/12 ,  C07D207/34 ,  C07D241/24 ,  C07D263/34 ,  C07D277/56 ,  C07D307/84 ,  C07D333/38 ,  C07D231/14 ,  C07D307/68

CPC分类号： C07D417/12 ,  C07D207/34 ,  C07D231/14 ,  C07D241/24 ,  C07D263/34 ,  C07D277/56 ,  C07D285/06 ,  C07D307/68 ,  C07D307/84 ,  C07D333/38

摘要： The invention features a series of heterocyclic derivatives that inhibit tumor necrosis factor alpha (TNF-α) induced necroptosis. The heterocyclic compounds of the invention are described by Formulas (I) and (Ia)-(Ie) and are shown to inhibit TNF-α induced necroptosis in FADD-deficient variant of human Jurkat T cells. The invention further features pharmaceutical compositions featuring the compounds of the invention. The compounds and compositions of the invention may also be used to treat disorders where necroptosis is likely to play a substantial role.

摘要翻译： 本发明具有一系列抑制肿瘤坏死因子α（TNF-α）诱导的人工坏死的杂环衍生物。 本发明的杂环化合物由式（I）和（Ia） - （Ie）描述，并且显示出抑制人Jurkat T细胞的FADD缺陷型变体中的TNF-α诱导的人工死亡。 本发明还涉及以本发明化合物为特征的药物组合物。 本发明的化合物和组合物也可以用于治疗棘球菌根可能起重要作用的病症。

公开(公告)号：US20230219898A1

公开(公告)日：2023-07-13

申请号：US18010642

申请日：2021-06-16

申请人： President and Fellows of Harvard College

发明人： Junying Yuan ,  Heng Zhao ,  Daichao Xu ,  Mingzhi Jin ,  Hong Zhu ,  Gregory D. Cuny

IPC分类号： C07D233/42 ,  C07D233/26 ,  C07C335/32 ,  C07D401/12 ,  C07D295/195 ,  C07D207/08 ,  A61K31/4178 ,  A61K31/4184

CPC分类号： C07D233/42 ,  C07D233/26 ,  C07C335/32 ,  C07D401/12 ,  C07D295/195 ,  C07D207/08 ,  A61K31/4178 ,  A61K31/4184

摘要： Disclosed herein are small molecules that inhibit apoptosis and promote autophagy through the TRADD pathway, and their use for treatment of neurodegenerative diseases. Methods of preparing these small molecules and medicinal efficacy are described.

公开(公告)号：US20190135718A1

公开(公告)日：2019-05-09

申请号：US16055898

申请日：2018-08-06

申请人： President and Fellows of Harvard College

发明人： Junying Yuan ,  Emily P. Hsu

IPC分类号： C07C35/37 ,  C07C33/38 ,  C07D233/02 ,  C07D211/78 ,  C07D498/08 ,  C07D495/04 ,  C07D417/12 ,  C07D405/06 ,  C07D403/12 ,  C07D403/06 ,  C07D333/20 ,  C07D307/52 ,  C07D277/46 ,  C07D231/56 ,  C07D231/12 ,  C07D231/06 ,  C07D215/08 ,  C07D211/90 ,  C07D209/08 ,  C07D277/18

摘要： The invention features a series of heterocyclic derivatives that inhibit tumor necrosis factor alpha (TNF-α) induced necroptosis. The heterocyclic compounds of the invention are described by Formulas (I)-(VIII) and by Compounds (1)-(7), (13)-(26), (27)-(33), (48)-(57), and (58)-(70). These necrostatins are shown to inhibit TNF-α induced necroptosis in FADD-deficient variant of human Jurkat T cells. The invention further features pharmaceutical compositions featuring necrostatins. The compounds and compositions of the invention may also be used to treat disorders where necroptosis is likely to play a substantial role.

公开(公告)号：US20170305824A1

公开(公告)日：2017-10-26

申请号：US15427699

申请日：2017-02-08

申请人： President and Fellows of Harvard College

发明人： Junying Yuan ,  Emily P. Hsu

IPC分类号： C07C35/37 ,  C07C33/38 ,  C07D417/12 ,  C07D405/06 ,  C07D403/12 ,  C07D403/06 ,  C07D333/20 ,  C07D307/52 ,  C07D277/46 ,  C07D277/18 ,  C07D233/02 ,  C07D231/56 ,  C07D231/12 ,  C07D231/06 ,  C07D215/08 ,  C07D211/90 ,  C07D211/78 ,  C07D209/08 ,  C07D495/04 ,  C07D498/08

CPC分类号： C07C35/37 ,  C07C33/38 ,  C07D209/08 ,  C07D211/78 ,  C07D211/90 ,  C07D215/08 ,  C07D231/06 ,  C07D231/12 ,  C07D231/56 ,  C07D233/02 ,  C07D277/18 ,  C07D277/46 ,  C07D307/52 ,  C07D333/20 ,  C07D403/06 ,  C07D403/12 ,  C07D405/06 ,  C07D417/12 ,  C07D495/04 ,  C07D498/08

摘要： The invention features a series of heterocyclic derivatives that inhibit tumor necrosis factor alpha (TNF-α) induced necroptosis. The heterocyclic compounds of the invention are described by Formulas (I)-(VIII) and by Compounds (1)-(7), (13)-(26), (27)-(33), (48)-(57), and (58)-(70). These necrostatins are shown to inhibit TNF-α induced necroptosis in FADD-deficient variant of human Jurkat T cells. The invention further features pharmaceutical compositions featuring necrostatins. The compounds and compositions of the invention may also be used to treat disorders where necroptosis is likely to play a substantial role.

公开(公告)号：US09725452B2

公开(公告)日：2017-08-08

申请号：US14214360

申请日：2014-03-14

申请人： President and Fellows of Harvard College ,  Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences ,  Tufts University ,  University of Houston

发明人： Junying Yuan ,  Alexei Degterev ,  Gregory D. Cuny

IPC分类号： A61K31/4025 ,  A61K31/404 ,  C07D207/30 ,  C07D209/04 ,  C07D487/04 ,  C07D401/14 ,  C07D471/04

CPC分类号： C07D487/04 ,  C07D401/14 ,  C07D471/04

摘要： The present invention relates to heterocyclic compounds (e.g., compounds described by Formula (I)) and pharmaceutically acceptable salts thereof. The invention also features pharmaceutical compositions that include these compounds and their use in therapy for treating conditions in which necroptosis is likely to play a substantial role. The heterocyclic compounds described herein can also achieve improved activity and selectivity towards RIP1 and/or RIP3.

公开(公告)号：US09499521B2

公开(公告)日：2016-11-22

申请号：US15194413

申请日：2016-06-27

申请人： President and Fellows of Harvard College ,  Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences

发明人： Junying Yuan ,  Yijun Zhou ,  Shan Qian ,  Dawei Ma

IPC分类号： C07D233/78 ,  C07D403/06

CPC分类号： C07D403/06 ,  A61P9/10 ,  A61P29/00 ,  C07D233/78

摘要： A compound having the following structure (I): or a pharmaceutically acceptable salt, prodrug, stereoisomer or tautomer thereof, is provided. Related compounds, methods for preparation of the same and uses of the compounds for treatment of various indications, including treatment of necrotic cell diseases and/or inflammation, are also provided.

摘要翻译： 或其药学上可接受的盐，前药，立体异构体或互变异构体。 还提供了相关化合物，其制备方法和用于治疗各种适应症的化合物的用途，包括治疗坏死性细胞疾病和/或炎症。

公开(公告)号：US10508102B2

公开(公告)日：2019-12-17

申请号：US15897787

申请日：2018-02-15

申请人： President and Fellows of Harvard College ,  Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences

发明人： Junying Yuan ,  Yijun Zhou ,  Shan Qian ,  Dawei Ma

IPC分类号： C07D403/06 ,  C07D233/78 ,  A61P29/00 ,  A61P9/10

摘要： A compound having the following structure (I): or a pharmaceutically acceptable salt, prodrug, stereoisomer or tautomer thereof, is provided. Related compounds, methods for preparation of the same and uses of the compounds for treatment of various indications, including treatment of necrotic cell diseases and/or inflammation, are also provided.