University of Michigan

Fuming Xu

Shaomeng Wang

Jiantao Hu

Bing Zhou

Longchuan Bai

Yang Hu

Chong Qin

Weiguo Xiang

Ester Fernandez-Salas

Donna McEachern

Chao-Yie Yang

Angelo Aguilar

Rohan Rej

Jiuling Yang

Yangbing Li

Xin Han

Zhuo Chen

Zhou Chen

The present disclosure provides compounds represented by Formula I and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein R, R, R, R, R, R4, Ar, L, X, Y, and B 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 degradation of BET bromodomains such as cancer. 

Fused 1,4-oxazepines as BET protein degraders

The present disclosure provides compounds represented by Formula (I): Formula (I) and the pharmaceutically acceptable salts and solvates thereof, wherein R, R, R, R, R, R, Y, &#x2550;, Ar, W, L, and B are as defined as set forth in the specification. The present disclosure also provides compounds of Formula (I)I for use to treat a condition or disorder responsive to inhibition and/or degradation of BET bromodomains such as cancer. 

BET bromodomain protein degraders with cleavable linkers

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 fused 1,4-diazepines represented by Formula (I): and the pharmaceutically acceptable salts and solvates thereof, wherein A, E, R, R, R, R, R, and Ar are as defined as set forth in the specification. The present disclosure is also directed to the use of compounds having Formula (I) to treat diseases, conditions, or disorders responsive to inhibition of BET bromodomain proteins such as cancer. 

Fused 1,4-diazepines as BET bromodomain inhibitors

The present disclosure provides compounds represented by Formula I: I, and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein R, R, R, R, R, Ar, L, X, Y, and B 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 degradation of BET bromodomains such as cancer. 

Fused 1,4-diazepines as BET protein degraders

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 compounds represented by Formula I: and the pharmaceutically acceptable salts, hydrates, and solvates thereof, wherein B, R, R, Q, Q&#x2033;, 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 a condition or disorder responsive to degradation of BET bromodomains such as cancer. 

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Ypsilanti, MI, United States of America

Fuming Xu