公开(公告)号：US20190127387A1

公开(公告)日：2019-05-02

申请号：US16091541

申请日：2017-04-06

Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN

Inventor： Shaomeng Wang ,  Yangbing Li ,  Jiuling Yang ,  Angelo Aguilar ,  Bing Zhou ,  Jiantao Hu ,  Fuming Xu ,  Rohan Rej ,  Xin Han

IPC: C07D487/10 ,  C07D401/04 ,  C07D401/14 ,  C07D417/14 ,  A61P35/00

Abstract: The present disclosure provides compounds represented by Formula I-A: A1-L1-B1 I-A and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein A1, B1, and L1 are as defined as set forth in the specification. The present disclosure also provides compounds of Formula I-A for use to treat a condition or disorder responsive to degradation of MDM2 protein such as cancer.

公开(公告)号：US20170210761A1

公开(公告)日：2017-07-27

申请号：US15443336

申请日：2017-02-27

Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN

Inventor： Shaomeng Wang ,  Yujun Zhao ,  Bing Zhou ,  Angelo Aguilar ,  Liu Liu ,  Longchuan Bai ,  Donna McEachern ,  Duxin Sun ,  Bo Wen ,  Ruijuan Luo ,  Ting Zhao ,  Arul Chinnaiyan ,  Irfan A. Asangani ,  Jeanne Stuckey ,  Jennifer Lynn Meagher ,  Xu Ran ,  Yang Hu

IPC: C07D519/00 ,  A61K31/519 ,  C07D487/14 ,  A61K31/538 ,  A61K31/437 ,  C07D487/04 ,  A61K31/5377

CPC classification number: C07D519/00 ,  A61K31/437 ,  A61K31/519 ,  A61K31/5377 ,  A61K31/538 ,  C07D487/04 ,  C07D487/14

Abstract: The present disclosure provides substituted 9H-pyrimido[4,5-b]indoles and 5H-pyrido[4,3-b]indoles and related analogs represented by Formula I: and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein R1a, A, B1, B2, G, X1, Y1, Y2, and Y3 are as defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula I to treat a condition or disorder responsive to inhibition of BET bromodomains. Compounds of the present disclosure are especially useful for treating cancer.

公开(公告)号：US20240166647A1

公开(公告)日：2024-05-23

申请号：US18279225

申请日：2022-03-03

Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN

Inventor： Shaomeng Wang ,  Tianfeng Xu ,  Dimin Wu ,  Zhixiang Chen ,  Xin Han ,  Weiguo Xiang ,  Rohan Rej ,  Angelo Aguilar ,  Longchuan Bai

IPC: C07D471/04 ,  C07D471/14 ,  C07D487/04 ,  C07D487/10 ,  C07D498/04 ,  C07D498/14

CPC classification number: C07D471/04 ,  C07D471/14 ,  C07D487/04 ,  C07D487/10 ,  C07D498/04 ,  C07D498/14

Abstract: The present disclosure provides compounds of Formula (I), wherein A, A1, A2, A3, R3, Z and Z1 are as defined in the specification, and the salts and solvates thereof. The present disclosure also relates to uses of the compounds as cereblon (CRBN) ubiquitination inhibitors, as synthetic intermediates that can be used to prepare PROTAC molecules, or as PROTAC molecules. The present disclosure also relates to uses of the compounds, e.g., in treating or preventing cancer and other diseases.

公开(公告)号：US11046703B2

公开(公告)日：2021-06-29

申请号：US16594344

申请日：2019-10-07

Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN

Inventor： Shaomeng Wang ,  Angelo Aguilar ,  Yangbing Li ,  Jiuling Yang ,  Donna McEachern

IPC: C07D487/10

Abstract: The present disclosure provides compounds represented by Formula I: wherein R1a, R1b, R2a, R2b, R3a, R3b, R4, A, L, X, Y, and Z are as defined as set forth in the specification. The present disclosure also provides compounds of Formula I for use to treat cancer or any other disease, condition, or disorder that is responsive to degradation of MDM2 protein.

公开(公告)号：US20210002289A1

公开(公告)日：2021-01-07

申请号：US17007191

申请日：2020-08-31

Applicant: The Regents of the University of Michigan

Inventor： Yangbing Li ,  Angelo Aguilar ,  Bing Zhou ,  Jiantao Hu ,  Fuming Xu ,  Chong Qin ,  Yang Hu ,  Weiguo Xiang ,  Rohan Rej ,  Jiuling Yang ,  Xin Han ,  Longchuan Bai ,  Chao-Yie Yang

IPC: C07D487/10 ,  C07D401/04 ,  C07D401/14 ,  C07D487/04 ,  C07D495/14

Abstract: The present disclosure provides compounds represented by Formula I: and the salts or solvates thereof, wherein X, L, Y, and B are as defined in the specification. Compounds having Formula I are immunomodulators and/or monofunctional synthetic intermediates that can be used to prepare small-molecule drug conjugates.

公开(公告)号：US20190152947A1

公开(公告)日：2019-05-23

申请号：US16098147

申请日：2017-05-02

Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN

Inventor： Shaomeng Wang ,  Angelo Aguilar ,  Ke Zheng ,  Shilin Xu ,  Tianfeng Xu ,  Denzil Bernard ,  Liyue Huang

IPC: C07D401/14 ,  A61P35/00 ,  C07D401/04 ,  C07D405/04 ,  C07D211/34

Abstract: The present disclosure provides compounds by Formula (I): (Formula(I)) and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein R2, R3a, R3b, A, G, X, and Y are as defined as set forth in the specification. The present disclosure also provides compounds of Formula (I) for use to treat a condition or disorder responsive to menin inhibition such as cancer.

公开(公告)号：US20150246923A1

公开(公告)日：2015-09-03

申请号：US14633360

申请日：2015-02-27

Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN

Inventor： Shaomeng Wang ,  Yujun Zhao ,  Bing Zhou ,  Angelo Aguilar ,  Liu Liu ,  Longchuan Bai ,  Donna McEachern ,  Duxin Sun ,  Bo Wen ,  Ruijuan Luo ,  Ting Zhao ,  Arul Chinnaiyan ,  Irfan A. Asangani ,  Jeanne Stuckey ,  Jennifer Lynn Meagher ,  Xu Ran

IPC: C07D487/04 ,  C07D487/14 ,  C07D519/00

CPC classification number: C07D519/00 ,  A61K31/437 ,  A61K31/519 ,  A61K31/5377 ,  A61K31/538 ,  C07D487/04 ,  C07D487/14

Abstract: The present disclosure provides substituted 9H-pyrimido[4,5-b]indoles and 5H-pyrido[4,3-b]indoles and related analogs represented by Formula I: and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein R1a, A, B1, B2, G, X1, Y1, Y2, and Y3 are as defined as set forth in the specification. The present disclosure is also directed to the use of compounds of Formula I to treat a condition or disorder responsive to inhibition of BET bromodomains. Compounds of the present disclosure are especially useful for treating cancer.

Abstract translation: 本公开提供取代的9H-嘧啶并[4,5-b]吲哚和5H-吡啶并[4,3-b]吲哚和由式I表示的相关类似物及其药学上可接受的盐，水合物和溶剂合物，其中R1a A，B1，B2，G，X1，Y1，Y2和Y3如说明书中所述。 本公开还涉及式I化合物用于治疗对抑制BET溴结构域有反应的病症或病症。 本公开的化合物特别可用于治疗癌症。

公开(公告)号：US10759808B2

公开(公告)日：2020-09-01

申请号：US16091544

申请日：2017-04-06

Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN

Inventor： Shaomeng Wang ,  Yangbing Li ,  Angelo Aguilar ,  Bing Zhou ,  Jiantao Hu ,  Fuming Xu ,  Chong Qin ,  Yang Hu ,  Weiguo Xiang ,  Rohan Rej ,  Jiuling Yang ,  Xin Han ,  Longchuan Bai ,  Chao-Yie Yang

IPC: C07D401/04 ,  C07D487/10 ,  C07D401/14 ,  C07D487/04 ,  C07D495/14

Abstract: The present disclosure provides compounds represented by Formula I: and the salts or solvates thereof, wherein X, L, Y, and B are as defined in the specification. Compounds having Formula I are immunomodulators and/or monofunctional synthetic intermediates that can be used to prepare small-molecule drug conjugates.

公开(公告)号：US20200022953A1

公开(公告)日：2020-01-23

申请号：US16497856

申请日：2018-03-30

Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN

Inventor： Shaomeng Wang ,  Angelo Aguilar ,  Shilin Xu ,  Liyue Huang ,  Jeanne Stuckey ,  Tianfeng Xu

IPC: A61K31/397 ,  C07D401/14 ,  C07D401/06 ,  C07D413/14 ,  C07D401/12 ,  C07D205/04 ,  A61K31/4523 ,  A61K31/4709 ,  A61K31/454 ,  A61K31/5377

Abstract: The present disclosure provides compounds represented by Formula (I): and the pharmaceutically acceptable salts and solvates thereof, wherein A, R1a, R1b, R1c, R1d, R2, R3, R8a, R8b, R10, X, Z2, m, and n are as defined as set forth in the specification. The present disclosure also provides compounds of Formula (I) for use to treat a condition or disorder responsive to menin inhibition such as cancer.

公开(公告)号：US20150299211A1

公开(公告)日：2015-10-22

申请号：US14688553

申请日：2015-04-16

Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN

Inventor： Shaomeng Wang ,  Angelo Aguilar ,  Liu Liu ,  Jianfeng Lu ,  Donna McEachern

IPC: C07D487/10 ,  A61K45/06 ,  A61N5/10 ,  A61K31/407

CPC classification number: C07D487/10 ,  A61K31/407 ,  A61K45/06 ,  A61N5/10 ,  A61N2005/1098

Abstract: Inhibitors of MDM2 and MDM2-related proteins and compositions containing the same are disclosed. Methods of using the MDM2 inhibitors in the treatment of diseases and conditions wherein inhibition of an interaction between p53 and MDM2 provides a benefit, like cancers, also are disclosed.

Abstract translation: 公开了MDM2和MDM2相关蛋白的抑制剂和含有它们的组合物。 还公开了使用MDM2抑制剂治疗其中抑制p53和MDM2之间的相互作用提供益处的疾病和病症的方法，如癌症。