US 12,318,452 B2
Degraders of WEE1 kinase
Nathanael S. Gray, Boston, MA (US); David Scott, Newton, MA (US); Zhengnian Li, Brookline, MA (US); Benika J. Pinch, Brookline, MA (US); Calla Olson, Brookline, MA (US); Eric S. Fischer, Chestnut Hill, MA (US); Radoslaw P. Nowak, Boston, MA (US); and Katherine A. Donovan, Brookline, MA (US)
Assigned to DANA-FARBER CANCER INSTITUTE, INC., Boston, MA (US)
Appl. No. 17/278,890
Filed by DANA-FARBER CANCER INSTITUTE, INC., Boston, MA (US)
PCT Filed Sep. 26, 2019, PCT No. PCT/US2019/053124
§ 371(c)(1), (2) Date Mar. 23, 2021,
PCT Pub. No. WO2020/069105, PCT Pub. Date Apr. 2, 2020.
Claims priority of provisional application 62/737,523, filed on Sep. 27, 2018.
Prior Publication US 2022/0047709 A1, Feb. 17, 2022
Int. Cl. A61K 47/55 (2017.01); A61K 31/502 (2006.01); A61K 31/519 (2006.01); A61K 45/06 (2006.01); A61K 47/54 (2017.01)
CPC A61K 47/55 (2017.08) [A61K 31/502 (2013.01); A61K 31/519 (2013.01); A61K 47/545 (2017.08); A61K 47/555 (2017.08)] 19 Claims
 
1. A compound having a structure represented by formula I:

OG Complex Work Unit Chemistry
wherein the targeting ligand is a moiety that binds Wee1 kinase and is represented by a structure selected from the group consisting of:

OG Complex Work Unit Chemistry

OG Complex Work Unit Chemistry
the degron is:

OG Complex Work Unit Chemistry
wherein Y′ is a bond, N, O or C;

OG Complex Work Unit Chemistry
wherein Z is a C5-C6 carbocyclic or a C5-C6 heterocyclic group; or

OG Complex Work Unit Chemistry
and
the linker is 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.