公开(公告)号：US20220274948A1

公开(公告)日：2022-09-01

申请号：US17740148

申请日：2022-05-09

Applicant: ST. JUDE CHILDREN'S RESEARCH HOSPITAL, INC.

Inventor： Marcus FISHER ,  Fatemeh KERAMATNIA ,  Kevin MCGOWAN ,  Jaeki MIN ,  Gisele A. NISHIGUCHI ,  Jeanine PRICE ,  Zoran RANKOVIC ,  Das SOURAV ,  Charles G. MULLIGHAN ,  Yunchao CHANG

IPC: C07D401/04 ,  A61K31/45 ,  A61K45/06 ,  C07D405/14 ,  C07D413/14 ,  C07D409/14 ,  A61P35/00 ,  A61P35/02

Abstract: In one aspect, the disclosure relates to substituted N-(2-(2,6-dioxopiperidinyl-3-yl)-1,3-dioxoisoindolin-5-ypaiylsulfo namide analogs that useful as modulators of cereblon (CRBN) activity, methods of making same, pharmaceutical compositions comprising same, and methods of treating various clinical conditions and disorders using same, e.g., a disorder of uncontrolled cellular proliferation, such as a cancer, which may be associated with cereblon protein dysfunction and/or a GSPT1 dysfunction. In various further aspects, the disclosed compounds can selectively modulate the degradation of GSPT1 protein, i.e., the disclosed compounds can act as GSPT1 degraders. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.