Eli Lilly and Company

St. Jude Children's Research Hospital

Zoran Rankovic

Timothy Paul Burkholder

Serge Louis Boulet

Patric James Hahn

Renato Alejandro Bauer

Leonard Larry Winneroski, Jr

Warren Jaye Porter

Brian Morgan Watson

Jose Eduardo Lopez

James Peter Beck

Brian Michael Mathes

Dustin James Mergott

Jaeki Min

Steven James Green

Raymond Gilmour

Yuan Shi

Sourav Das

Charles G Mullighan

Fatemeh Keramatnia

Jeanine Price

Yunchao Chang

Kevin Mcgowan

Gisele A Nishiguchi

Santiago Carballares Martin

Wenceslao Lumeras Amador

Marcus Fisher

Marcus Fischer

Jr Leonard Larry Winneroski

In one aspect, the disclosure relates to substituted N-(2-(2,6-dioxopiperidinyl-3-yl)-1,3-dioxoisoindolin-5-yl)arylsulfo 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.

Substituted N-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)arylsulfonamide analogs as modulators of cereblon protein

In one aspect, the disclosure relates to substituted N-(2-(2,6-dioxopiperidinyl-3-yl)-1,3-dioxoisoindolin-5-yl)arylsulfonamide 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.

A compound, as defined herein, or pharmaceutical composition containing the compound, for use in treating IDH1 or IDH2 mutant cancer and having the structure: (I). 

7-phenylethylamino-4H-pyrimido[4,5-d][1,3]oxazin-2-one compounds as mutant IDH1 and IDH2 inhibitors

The present application provides compounds of Formula I: Formula (I) that are useful as inhibitors of mutant IDH1, pharmaceutical compositions, and uses for the treatment of cancer. 

Mutant IDH1 inhibitors

The present invention provides compounds of Formula I: wherein A is selected from the group consisting of; Ris H or F;Ris H, &#x2014;CHOH, C1-C3 alkyl, Ris H, F, or CN;Ris H, F; or CN; andRis H, &#x2014;CH, or &#x2014;OCH;or a pharmaceutically acceptable salt thereof.

Tetrahydropyrrolothiazine compounds

The present invention provides compounds of Formula I: wherein A is selected from the group consisting of;  

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Memphis, TN, United States of America

Zoran Rankovic