University of Michigan

Sanofi

Angelo Aguilar

Shaomeng Wang

Liu Liu

Donna McEachern

Longchuan Bai

Duxin Sun

Bing Zhou

Jeanne Stuckey

Yujun Zhao

Xiaoqin Li

Yang Hu

Jennifer Lynn Meagher

Jianfang Chen

Yangbing Li

Jiuling Yang

Arul M Chinnaiyan

Chao-Yie Yang

Fuming Xu

Jiantao Hu

Irfan A Asangani

Rohan Rej

Xu Ran

Ruijuan Luo

Liyue Huang

Bo Wen

Shilin Xu

Ting Zhao

Tianfeng Xu

Xin Han

Donna Mceachern

Wei Sun

Jianfeng Lu

Chong Qin

Denzil Bernard

Haibin Zhou

Weiguo Xiang

Donna McEachem

Carlos Garcia-Echeverria

Ke Zheng

Donna Mceacherm

Ke Zhang

The present disclosure provides compounds represented by Formula I-A: A-L-BI-A and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein A, B, 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.

MDM2 protein degraders

The present disclosure provides compounds represented by Formula (I): and the pharmaceutically acceptable salts and solvates thereof, wherein A, R, R, R, R, R, R, R, R, R, X, Z, 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. 

Piperidines as covalent menin inhibitors

The present disclosure provides compounds represented by Formula I: wherein R, R, R, R, R, R, R, 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.

Small molecule MDM2 protein degraders

The present disclosure provides compounds by Formula (I): (Formula (I)) and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein R, R, R, 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. 

Piperidines as menin inhibitors

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. 

Monofunctional intermediates for ligand-dependent target protein degradation

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 R, W, B, B, G, X, Y, Y, and Yare 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 such as cancer. The present disclosure is also directed to the use of compound of Formula I as synthetic intermediates. 

9H-pyrimido [4,5-B] indoles as BET bromodomain inhibitors

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 R, A, B, B, G, X, Y, Y, and Yare 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.

9H-pyrimido [4,5-b]indoles and related analogs as BET bromodomain inhibitors

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.

MDM2 inhibitors and therapeutic methods using the same

9H-pyrimido[4,5-B]indoles and related analogs as BET bromodomain inhibitors

Inhibitors of Bcl-2/Bcl-xL and compositions containing the same are disclosed. Methods of using the Bcl-2/Bcl-xL inhibitors in the treatment of diseases and conditions wherein inhibition of Bcl-2/Bcl-xL provides a benefit, like cancers, also are disclosed.

Bcl-2/Bcl-xL inhibitors and therapeutic methods using the same

BCL-2/BCL-XL inhibitors and therapeutic methods using the same

Provided herein are compounds, compositions, and methods in the field of medicinal chemistry. The compounds and compositions provided herein relate to spiro-oxindoles which function as antagonists of the interaction between p53 and MDM2, and their use as therapeutics for the treatment of cancer and other diseases.

Spiro-oxindole MDM2 antagonists

Growing community of inventors

Ann Arbor, MI, United States of America

Angelo Aguilar