Small molecule tracer for imaging alpha-synuclein aggregates

Patent metadata

Field	Value
Publication number	US-2025049966-A1
Application number	US-202218718239-A
Country	US
Kind code	A1
Filing date	Dec 12, 2022
Priority date	Dec 13, 2021
Publication date	Feb 13, 2025
Grant date	—

Abstract

The invention discloses a type of compound that can specifically bind to α-synuclein aggregates represented by Formula I, a radio-labelled compound thereof, a preparation method, and its use. The compound can be used as a tracer for optical imaging of α-synuclein aggregates in biological samples or in vivo (such as the brain). After radio-labelled, the compound of the invention can be used as a radio imaging tracer for PET, SPECT, and other imaging techniques to realize the detection of α-synuclein lesions by non-invasive visualization in vivo (such as the brain).

First claim

1 . A compound represented by general Formula I, its pharmaceutically acceptable salt or solvate, which can be used as a tracer for the imaging diagnosis of α-synuclein accumulation diseases,

wherein,
Ring A is selected from benzene, pyridine, and pyrimidine;
R 1 is selected from 4-6 membered nitrogen-containing cycloalkyl, amino group substituted with N, N-diC 1-3 alkyl, C 1-3 alkoxyl, nitro, halogen;
Ring B is selected from pyridine, piperazine, piperazinone;
R 2 is selected from halogen, hydroxyl, C 1-3 alkyl, C 1-4 alkoxyl, and halogenated C 1-4 alkoxyl;

wherein the halogen is selected from fluorine, bromine, or iodine.

2 . A compound, its pharmaceutically acceptable salt or solvate thereof according to claim 1 , wherein R 1 is preferably tetrahydropyrrole, N, N-dimethylamino, or methoxyl.

3 . A compound, its pharmaceutically acceptable salt or solvate thereof according to claim 1 , wherein one or more atoms of the compound of Formula I are the radioisotopes of that atom, of which preferably taken from 11 C, 13 N, 15 O, 18 F, 76 Br, 123 I, 125 I, and 131 I.

4 . A compound, its pharmaceutically acceptable salt or solvate thereof according to claim 3 , wherein the compound represented by Formula I is selected from the following structures:

wherein one of the atoms marked with * is a radioisotope of that atom at least.

5 . A compound selected from the following structures, which is used as a precursor for the synthesis of the compound according to claim 4 ,

wherein, R 3 is independently selected from hydroxyl, fluorine, bromine, iodine, nitro, borate group, TsO-(CH 2 ) m —, MsO-(CH 2 ) m —, wherein m is an integer from 0 to 4; R 4 is independently selected from hydrogen, C 1-3 alkyl, and 4-6 membered nitrogen-containing cycloalkyl by cyclization of NR 4 R 4 , wherein one of the atoms marked with * is a radioisotope of that atom at least.

6 . (canceled)

7 . (canceled)

8 . The use of a compound, pharmaceutically acceptable salt, or solvate thereof according to claim 1 , wherein a compound represented by Formula I or its pharmaceutically acceptable salt or solvate thereof can bind to α-synuclein aggregates and used as a tracer to image the diseases caused by α-synuclein accumulation.

Assignees

• Univ Fudan

Inventors

• Chu Yong
• Wang Jian
• Bian Jiang
• Liu Yiqi
• Lin Xin
• Qiu Chenyang
• He Jie
• Ye Deyong

Classifications

• A61K51/0459

  having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine · CPC title

• A61K51/0455 Primary

  having six-membered rings with one nitrogen as the only ring hetero atom · CPC title

• C07D401/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D471/04

  Ortho-condensed systems · CPC title

• C07D413/04 Primary

  directly linked by a ring-member-to-ring-member bond · CPC title