Compounds for diagnosis

Patent metadata

Field	Value
Publication number	US-12552800-B2
Application number	US-202117923771-A
Country	US
Kind code	B2
Filing date	May 7, 2021
Priority date	May 7, 2020
Publication date	Feb 17, 2026
Grant date	Feb 17, 2026

Abstract

The present invention relates to novel compounds of formula (I), or a detectably labelled compound, stereoisomer, racemic mixture, pharmaceutically acceptable salt, hydrate, or solvate thereof, that can be employed in the imaging of alpha-synuclein aggregates and determining an amount thereof. Furthermore, the compounds can be used for diagnosing a disease, disorder or abnormality associated with an alpha-synuclein aggregates, including, but not limited to, Lewy bodies and/or Lewy neurites (such as Parkinson's disease), determining a predisposition to such a disease, disorder or abnormality, prognosing such a disease, disorder or abnormality, monitoring the evolution of the disease in a patient suffering from such a disease, disorder or abnormality, monitoring the progression of such a disease, disorder or abnormality and predicting responsiveness of a patient suffering from such a disease, disorder or abnormality to a treatment thereof.

First claim

The invention claimed is:

1 . A compound of formula (I)

or a detectably labelled compound, stereoisomer, racemic mixture, pharmaceutically acceptable salt, hydrate, or solvate thereof,
wherein

is an aryl or a heteroaryl which is directionally selected from the group consisting of:

R 0 is H or C 1 -C 4 alkyl;
R 1 is —CN; or halo; or C 1 -C 4 alkyl; or C 1 -C 4 alkoxy; or —N(C 1 -C 4 alkyl) 2 ; or —NH(C 1 -C 4 alkyl); or H;
or
R 1 is —NH—C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkyl, or heterocyclyl, wherein the heterocyclyl is a 4- to 6-membered non-aromatic monocyclic ring radical containing 1 or 2 heteroatoms, each of which is optionally substituted with at least one halo;
R 2 is selected from the group consisting of:

wherein
R 2a , R 2a′ are independently H, or F;
R 2b is independently F, OH, C 1 -C 4 alkyl, haloC 1 -C 4 alkyl, NH 2 , CN, or C 1 -C 4 alkoxy;
R 2c , R 2c′ are independently H, F, OH, OCH 3 , or CH 3 ;
R 2d is H, F, or OH;
R 2e is H, OH, CH 3 , or F;
Z is independently N, NH, N(C 1 -C 4 alkyl), N(haloC 1 -C 4 alkyl), O, or S;
Z 1 is independently N, NH, O, or S;
p is 0, 1 or 2;
m is 0 or 1;
as valency permits, is a combination of single and double bonds; and
* is the position of bonding.

2 . The compound according to claim 1 , having a formula (IIa), (IIb), (IIIa), (IIIb), or (IIIc)

or a detectably labelled compound, stereoisomer, racemic mixture, pharmaceutically acceptable salt, hydrate, or solvate thereof.

3 . The compound according to claim 1 , wherein R 1 is —NH—C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkyl, or heterocyclyl, each of which is optionally substituted with at least one halo, wherein the heterocyclyl is a 4- to 6-membered non-aromatic monocyclic ring radical containing 1 or 2 heteroatoms.

4 . A compound, which is one of the following compounds:

or a detectably labelled compound, stereoisomer, racemic mixture, pharmaceutically acceptable salt, hydrate, or solvate thereof.

5 . A detectably labelled compound of formula (I)

stereoisomer, racemic mixture, pharmaceutically acceptable salt, hydrate, or solvate thereof, wherein

is an aryl or a heteroaryl which is directionally selected from the group consisting of:

R 0 is H or C 1 -C 4 alkyl;
R 1 is —CN; or halo; or C 1 -C 4 alkyl; or C 1 -C 4 alkoxy: or —N(C 1 -C 4 alkyl) 2 ; or —NH(C 1 -C 4 alkyl); or H;
or
R 1 is —NH—C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkyl, or heterocyclyl, which is a 4- to 6-membered non-aromatic monocyclic ring radical containing 1 or 2 heteroatoms, each of which is optionally substituted with at least one halo;
R 2 is selected from the group consisting of:

wherein
R 2a , R 2a′ are independently H, or F;
R 2b is independently F, OH, C 1 -C 4 alkyl, haloC 1 -C 4 alkyl, NH 2 , CN, or C 1 -C 4 alkoxy;
R 2c , R 2c′ are independently H, F, OH, OCH 3 , or CH 3 ;
R 2d is H, F, or OH;
R 2e is H, OH, CH 3 , or F;
Z is independently N, NH, N(C 1 -C 4 alkyl), N(haloC 1 -C 4 alkyl), O, or S;
Z 1 is independently N, NH, O, or S;
p is 0, 1 or 2;
m is 0 or 1;
as valency permits, is a combination of single and double bonds; and
* is the position of bonding,
wherein the compound is a detectably labelled compound.

6 .

Assignees

• Ac Immune Sa

Inventors

• Molette Jerome

Classifications

• C07B2200/05

  Isotopically modified compounds, e.g. labelled · CPC title

• C07B59/002

  Heterocyclic compounds · CPC title

• A61K51/0463

  having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines · CPC title

• A61K51/0459

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

• A61K51/0455

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