	US 11,981,678 B2
	Substituted [1,2,4]triazolo[4,3-c]pyrimidin-5-amines and proteolysis-targeting chimeric derivatives thereof (PROTACs) that induce degradation of embryonic ectoderm development (EED) protein
Gary E. Schiltz, Naperville, IL (US); and Jindan Yu, Evanston, IL (US)
Assigned to Northwestern University, Evanston, IL (US)
Filed by Northwestern University, Evanston, IL (US)
Filed on Apr. 29, 2022, as Appl. No. 17/733,752.
Claims priority of provisional application 63/201,434, filed on Apr. 29, 2021.
Prior Publication US 2022/0372039 A1, Nov. 24, 2022
Int. Cl. A61K 31/519 (2006.01); C07D 487/04 (2006.01)

CPC C07D 487/04 (2013.01)

4 Claims

1. A compound of the following formula:

M_EED-L-M_E3

or a pharmaceutically acceptable salt or stereoisomer thereof,

wherein:

M_EEDis Formula II:

wherein:

n is 1;

x is 1;

R²is a bond or —C(O)—; and

* is the point of attachment to the —CH₂— of the —(CH₂CH₂O)_n— of L;

(i) L is a linker of the following formula:

*—(CH₂CH₂O)_nCH₂CH₂-+

wherein:

n is 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20;

* is the point of attachment to the piperazinylene nitrogen atom or —C(O)— of M_EED; and

+ is the point of attachment to the —C(O)—, —NH—, or —O— of M_E3; or

(ii) L is a linker of the following formula:

*—(CH₂CH₂O)_nCH₂CH₂C(O)NHCH₂CH₂-+

wherein:

n is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20;

* is the point of attachment to the piperazinylene nitrogen atom or —C(O)— of M_EED; and

+ is the point of attachment to the —C(O)—, —NH—, or —O— of M_E3; and

M_E3is:

wherein:

+ is the point of attachment to the —CH₂— of L.

4. A pharmaceutical composition comprising a pharmaceutically acceptable carrier, excipient, or diluent and a compound of claim 1, or a pharmaceutically acceptable salt or stereoisomer thereof.