US 12,030,892 B2
CRBN modulators
Nathanael Gray, Boston, MA (US); Tinghu Zhang, Brookline, MA (US); Eric Fischer, Chestnut Hill, MA (US); Alyssa Verano, Allston, MA (US); Zhixiang He, Brookline, MA (US); Guangyan Du, Jamaica Plain, MA (US); Katherine Donovan, Boston, MA (US); Radoslaw Nowak, Boston, MA (US); and Jing Ting Christine Yuan, Brookline, MA (US)
Assigned to DANA-FARBER CANCER INSTITUTE, INC., Boston, MA (US)
Appl. No. 17/255,750
Filed by DANA-FARBER CANCER INSTITUTE, INC., Boston, MA (US)
PCT Filed Jun. 27, 2019, PCT No. PCT/US2019/039553
§ 371(c)(1), (2) Date Dec. 23, 2020,
PCT Pub. No. WO2020/006262, PCT Pub. Date Jan. 2, 2020.
Claims priority of provisional application 62/692,189, filed on Jun. 29, 2018.
Prior Publication US 2021/0277018 A1, Sep. 9, 2021
Int. Cl. C07D 495/14 (2006.01); A61K 47/54 (2017.01); C07D 401/04 (2006.01)
CPC C07D 495/14 (2013.01) [A61K 47/545 (2017.08); C07D 401/04 (2013.01)] 19 Claims
 
1. A compound having a structure represented by formula (I):

OG Complex Work Unit Chemistry
wherein R1 and R2 independently represent H, halo, hydroxyl, optionally substituted C1-C5 alkyl, optionally substituted C1-C5 alkoxy, or optionally substituted amine, optionally substituted amide, acyl, or

OG Complex Work Unit Chemistry
 provided that one of R1 and R2 represents

OG Complex Work Unit Chemistry
wherein the targeting ligand (TL) has a structure represented by:

OG Complex Work Unit Chemistry
the linker (L) comprises an alkylene chain or a polyethylene glycol chain, either of which may be interrupted by, and/or terminate at either or both termini in at least one of —O—, —S—, —N(R′)—, —C≡C—, —C(O)—, —C(O)O—, —OC(O)—, —OC(O)O—, —C(NOR′)—, —C(O)N(R′)—, —C(O)N(R′)C(O)—, —C(O)N(R′)C(O)N(R′)—, —N(R′)C(O)—, —N(R′)C(O)N(R′)—, —N(R′)C(O)O—, —OC(O)N(R′)—, —C(NR′)—, —N(R′)C(NR′)—, —C(NR′)N(R′)—, —N(R′)C(NR′)N(R′)—, —OB(Me)O—, —S(O)2—, —OS(O)—, —S(O)O—, —S(O)—, —OS(O)2—, —S(O)2O—, —N(R′)S(O)2—, —S(O)2N(R′)—, —N(R′)S(O)—, —S(O)N(R′)—, —N(R′)S(O)2N(R′)—, —N(R′)S(O)N(R′)—, C3-C12 carbocyclene, 3- to 12-membered heterocyclene, 5- to 12-membered heteroarylene or any combination thereof, wherein R′ is H or C1-C6 alkyl, wherein the interrupting and the one or both terminating groups may be the same or different,
or a pharmaceutically acceptable salt or stereoisomer thereof.