Substituted [1,2,4]triazolo[4,3-c]pyrimidines that induce degradation of embryonic ectoderm development (EED) protein

Patent metadata

Field	Value
Publication number	US-12492209-B2
Application number	US-202418632213-A
Country	US
Kind code	B2
Filing date	Apr 10, 2024
Priority date	Apr 29, 2021
Publication date	Dec 9, 2025
Grant date	Dec 9, 2025

Abstract

Disclosed are compounds that bind to embryonic ectoderm development (EED) protein and proteolysis-targeting chimeric (PROTAC) derivatives thereof that induce degradation of EED. The disclosed compounds may be characterized as substituted [1,2,4]triazolo[4,3-c]pyrimidin-5-amine compounds having the Formula I:

where R 1 is as disclosed herein. The disclosed PROTAC derivatives thereof typically include a first targeting moiety that binds to BED (M EED ) which may be derived from the disclosed [1,2,4]triazolo[4,3-c]pyrimidin-5-amine compounds having the Formula I that bind to EED. The first targeting moiety typically is linked via a bond or a linker (L) to a second targeting moiety that binds to an E3 ubiquitin ligase (M E3 ). As such, the disclosed PROTACS may be described as having a formula M EED -L-M E3 or M E3 -L-M EED .

First claim

We claim:

1 . A compound of Formula I:

or a pharmaceutically acceptable salt thereof,
wherein:
R 1 is:

R 2 is alkyl, C(O)H, C(O)CH 2 CH(CH 2 CH 2 CH 3 ) 2 , C(O)—(CH 2 ) m CH 3 , C(O)CH 2 OCH 3 , C(O)—(CH 2 CH 2 O)˜H, C(O)—(CH 2 CH 2 O) m CH 3 , O(alkyl), S(O) 2 H, or S(O) 2 CH 3 ;
m is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,16, 17, 18, 19, or 20;
n is 1; and
x is 1;
with the proviso that if R 2 is C(O)—(CH 2 CH 2 O) m CH 3 , then m is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,16, 17, 18, 19, or 20.

2 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is:

3 . The compound of claim 1 , wherein the compound is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

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

5 . A method for treating cancer in a subject, wherein the method comprises administering to the subject tin need thereof a therapeutically effective amount of the pharmaceutical composition of claim 4 .

6 . The method of claim 5 , wherein the cancer is selected from the group consisting of breast cancer, cancer of the central nervous system, colon cancer, leukemia, melanoma, multiple myeloma, non-small cell lung cancer, ovarian cancer, prostate cancer, and renal cancer.

Assignees

• Univ Northwestern

Inventors

• Schiltz Gary E
• Yu Jindan

Classifications

• C07D487/04 Primary

  Ortho-condensed systems · CPC title