Small molecule degraders of helios and methods of use
AssigneeDana-Farber Cancer Institute, Inc.
InventorsAlyssa Verano, Eric Wang, Radoslaw Nowak, Jing Ting Christine Yuan, Nathanael Gray, Eric Fischer, Tinghu Zhang, Hu Liu
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Abstract
Disclosed are compounds and pharmaceutically acceptable salts and stereoisomers thereof that may cause degradation of various proteins e.g., IKZF2 (Helios). Also disclosed are pharmaceutical compositions containing same, and methods of making and using the compounds to treat diseases and disorders characterized or mediated by aberrant protein activity.
Claims63
A compound represented by a structure of formula I:
- wherein:
- Q represents CH2 or C═O;
- X represents NR, O, or S, wherein R is H or Me;
- Y is absent or represents optionally substituted C1-C5 alkyl, optionally substituted aryl, or optionally substituted heteroaryl;
- is absent or represents
- wherein n is 2 or 3;
- wherein n′ is 0 or 1;
- wherein Rc is halo, optionally substituted C1-C2 alkyl, optionally substituted aryl, or optionally substituted heteroaryl;
- wherein R″ represents optionally substituted C1-C2 alkyl;
- wherein Z represents
- W1 and W2 are independently absent or independently represent CH, CH2, O, O—CH2, NH—CH2 or optionally substituted amino;
- M represents a 5- or 6-membered cyclic group;
- and
- Ar represents optionally substituted phenyl or benzyl;
- wherein
- or Y is absent;
- or a pharmaceutically acceptable salt or stereoisomer thereof.
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A compound represented by a structure of formula II:
- wherein:
- represents
- wherein R4 is H or a substituent;
- R5 represents H, -Me, -Et,
- W3 and W4 are independently absent or independently represent CH2, NH, or NH—CH2;
- and
- Ar1 is optionally substituted aryl or heteroaryl;
- or a pharmaceutically acceptable salt or stereoisomer thereof.
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A compound represented by a structure of formula III:
- wherein
- W5 and W6 each independently represents —CH2— or —NH—, provided that one of W5 and W6 is
- —NH—;
- and
- Ar2 is optionally substituted aryl or heteroaryl;
- or a pharmaceutically acceptable salt or stereoisomer thereof.
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Dependencies are inferred from the claim text.