Granted Patent
B2
US 12,410,171 · App. 17/904,822 · Granted Sep 9, 2025
Tropomyosin receptor kinase (TRK) degradation compounds and methods of use
Inventors:
Jing Liu (Oradell, NJ); Jialiang Wang (Nashville, TN); Xiaoran Han (Shanghai, CN); Liqun Chen (Shanghai, CN); Chengwei Zhang (Shanghai, CN)
Assignee:
CULLGEN (SHANGHAI), INC.
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Abstract
This disclosure relates to bivalent compounds (e.g., bi-functional small molecule compounds), compositions comprising one or more of the bivalent compounds, and to methods of use the bivalent compounds for the treatment of certain disease in a subject in need thereof. The disclosure also relates to methods for identifying such bivalent compounds.
Claims (15)
1. A bivalent compound, selected from the group consisting of:
(S)-N-(5-(3,5-Difluorobenzyl)-1H-indazol-3-yl)-4-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidin-3-yl)methyl)piperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide (TR-341); and
(R)-N-(5-(3,5-Difluorobenzyl)-1H-indazol-3-yl)-4-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidin-3-yl)methyl)piperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide (TR-342);
or a pharmaceutically acceptable salt thereof.
2. The bivalent compound of claim 1 , which is(S)-N-(5-(3,5-Difluorobenzyl)-1H-indazol-3-yl)-4-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidin-3-yl)methyl)piperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide (TR-341), or a pharmaceutically acceptable salt thereof.
3. The bivalent compound of claim 1 , which is (R)-N-(5-(3,5-Difluorobenzyl)-1H-indazol-3-yl)-4-(4-((1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)azetidin-3-yl)methyl)piperazin-1-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)benzamide (TR-342), or a pharmaceutically acceptable salt thereof.
4. A pharmaceutical composition comprising a bivalent compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.
5. A method of treating a tropomyosin receptor kinase (TRK)-mediated disease, comprising administering to a subject with a TRK-mediated disease a bivalent compound of claim 1 , or a pharmaceutically acceptable salt thereof.
6. The method of claim 5 , wherein the TRK-mediated disease results from TRK expression, mutation, splicing, or fusion.
7. The method of claim 5 , wherein the TRK-mediated disease is cancer.
8. The method of claim 7 , wherein the cancer is a relapsed cancer.
9. The method of claim 7 , wherein the cancer is refractory to one or more previous treatments.
10. The method of claim 7 , further comprising administering to the subject an additional therapeutic regimen for treating cancer.
11. The method of claim 10 , wherein the additional therapeutic regimen is selected from the group consisting of surgery, chemotherapy, radiation therapy, hormone therapy, and immunotherapy.
12. The method of claim 5 , wherein the TRK-mediated disease is acute pain or chronic pain.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jan 9, 2023
From: LIU, JING; PLEWE, MICHAEL BRUNO; WANG, JIALIANG; HAN, XIAORAN; CHEN, LIQUN; ZHANG, CHENGWEI
To: CULLGEN (SHANGHAI), INC.
Reel/Frame 062314/0507 →
Priority Claims (1)
WO PCT/CN2020/076748
· Feb 26, 2020
· international
Continuity (1)
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