US 12,227,488 B2
Small molecule degraders of Helios and methods of use
Alyssa Verano, Allston, MA (US); Eric Wang, Brookline, MA (US); Radoslaw Nowak, Boston, MA (US); Jing Ting Christine Yuan, Brookline, MA (US); Nathanael Gray, Boston, MA (US); Eric Fischer, Chestnut Hill, MA (US); Tinghu Zhang, Brookline, MA (US); and Hu Liu, Newton, MA (US)
Assigned to DANA-FARBER CANCER INSTITUTE, INC., Boston, MA (US)
Appl. No. 17/298,823
Filed by DANA-FARBER CANCER INSTITUTE, INC., Boston, MA (US)
PCT Filed Dec. 3, 2019, PCT No. PCT/US2019/064169
§ 371(c)(1), (2) Date Jun. 1, 2021,
PCT Pub. No. WO2020/117759, PCT Pub. Date Jun. 11, 2020.
Claims priority of provisional application 62/938,410, filed on Nov. 21, 2019.
Claims priority of provisional application 62/774,482, filed on Dec. 3, 2018.
Prior Publication US 2022/0177443 A1, Jun. 9, 2022
Int. Cl. C07D 401/04 (2006.01); A61P 35/00 (2006.01); C07D 401/14 (2006.01); C07D 417/14 (2006.01)
CPC C07D 401/04 (2013.01) [A61P 35/00 (2018.01); C07D 401/14 (2013.01); C07D 417/14 (2013.01)] 47 Claims
 
1. A compound represented by a structure of formula I:

OG Complex Work Unit Chemistry
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 phenyl, optionally substituted benzyl, optionally substituted pyridinyl, optionally substituted imidazolyl, optionally substituted pyrazolyl, optionally substituted triazolyl, optionally substituted tetrazolyl, optionally substituted thiazolyl, optionally substituted quinolinyl, optionally substituted indolyl, or optionally substituted indazolyl;

OG Complex Work Unit Chemistry
is absent or represents

OG Complex Work Unit Chemistry
wherein n is 2 or 3; wherein n′ is 0 or 1;
wherein R′ 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

OG Complex Work Unit Chemistry
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

OG Complex Work Unit Chemistry
wherein each R3 is independently alkyl, halo, trifluoromethyl, aryl, heteroaryl, or benzyl, and n″ is 0, 1, or 2;
wherein

OG Complex Work Unit Chemistry
or Y is absent;
or a pharmaceutically acceptable salt or stereoisomer thereof,
wherein the optional substituent is independently alkyl, alkoxy, haloalkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, aralkyl, halo, hydroxyl, aryloxy, alkylthio, arylthio, cyano, carbonyl, carboxyl, amino, amido, thio, sulfinyl, sulfonyl, sulfinamide, sulfonamide, urea, carbamate, or an amino acid.