US 12,465,648 B2
Heterobifunctional compounds as degraders of HPK1
Jian Jin, New York, NY (US); Steven Burakoff, New York, NY (US); H. Umit Kaniskan, New York, NY (US); Sansana Sawasdikosol, New York, NY (US); He Chen, New York, NY (US); Joshua Brody, New York, NY (US); and Nina Bhardwaj, New York, NY (US)
Assigned to Icahn School of Medicine at Mount Sinai, New York, NY (US)
Appl. No. 17/604,636
Filed by ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI, New York, NY (US)
PCT Filed May 5, 2020, PCT No. PCT/US2020/031527
§ 371(c)(1), (2) Date Oct. 18, 2021,
PCT Pub. No. WO2020/227325, PCT Pub. Date Nov. 12, 2020.
Claims priority of provisional application 62/843,816, filed on May 6, 2019.
Prior Publication US 2023/0022524 A1, Jan. 26, 2023
Int. Cl. A61K 47/55 (2017.01); A61K 39/395 (2006.01); A61K 47/54 (2017.01); A61P 35/00 (2006.01); C07D 401/14 (2006.01); C07D 403/14 (2006.01); C07D 417/14 (2006.01); C07D 487/04 (2006.01)
CPC A61K 47/55 (2017.08) [A61K 39/3955 (2013.01); A61K 47/545 (2017.08); A61P 35/00 (2018.01); C07D 401/14 (2013.01); C07D 403/14 (2013.01); C07D 417/14 (2013.01); C07D 487/04 (2013.01)] 3 Claims
OG exemplary drawing
 
1. A bivalent compound comprising a hematopoietic progenitor kinase 1 (HPK1) ligand conjugated to a degradation/disruption tag, selected from the group consisting of:
2-(2,6-dioxopiperidin-3-yl)-5-((7-(4-(4-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)piperazin-1-yl)-7-oxoheptyl)amino)isoindoline-1,3-dione (HC90-46);
2-(2,6-dioxopiperidin-3-yl)-4-((3-(4-(4-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)piperazin-1-yl)-3-oxopropyl)amino)isoindoline-1,3-dione (HC90-50);
2-(2,6-dioxopiperidin-3-yl)-4-((4-(4-(4-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)piperazin-1-yl)-4-oxobutyl)amino)isoindoline-1,3-dione (HC90-51);
2-(2,6-dioxopiperidin-3-yl)-4-((5-(4-(4-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)piperazin-1-yl)-5-oxopentyl)amino)isoindoline-1,3-dione (HC90-52);
2-(2,6-dioxopiperidin-3-yl)-4-((6-(4-(4-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)piperazin-1-yl)-6-oxohexyl)amino)isoindoline-1,3-dione (HC90-53);
2-(2,6-dioxopiperidin-3-yl)-4-((7-(4-(4-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)piperazin-1-yl)-7-oxoheptyl)amino)isoindoline-1,3-dione (HC90-54);
N-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)ethyl)-2-(4-(4-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)piperazin-1-yl)acetamide (HC90-86);
N-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)amino)butyl)-2-(4-(4-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)piperazin-1-yl)acetamide (HC90-88);
N-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyl)-2-(4-(4-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)piperazin-1-yl)acetamide (HC90-104);
2-(2,6-dioxopiperidin-3-yl)-4-((8-(4-(4-(5-(2-fluoro-6-methoxyphenyl)-1H-pyrazolo[4,3-d]pyrimidin-3-yl)phenyl)piperazin-1-yl)-8-oxooctyl)amino)isoindoline-1,3-dione (HC90-117);
and pharmaceutically acceptable salts thereof.